KR20190016302A - 치주질환 진단용 바이오마커 - Google Patents
치주질환 진단용 바이오마커 Download PDFInfo
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Abstract
본 발명은 노인성 치주질환 진단용 조성물에 관한 것으로, 본 발명의 조성물은 노인성 치주염의 염증관련 질환의 예방을 위한 진단 및 약물 반응 진단, 치료용 물질의 타겟 및 치료 물질 개발 스크리닝을 위한 바이오마커로써 유용하게 활용될 수 있을 것으로 기대된다.
Description
본 발명은 치주질환 진단용 바이오마커에 관한 것이다.
치주질환은 흔히 풍치라고도 하는데, 병의 정도에 따라 치은염(gingivitis)과 치주염(periodontitis)으로 나뉜다. 비교적 가볍고 회복이 빠른 형태의 치주질환으로 잇몸 즉, 연조직에만 국한된 형태를 치은염이라고 하고, 이러한 염증이 잇몸과 잇몸뼈 주변까지 진행된 경우를 치주염이라고 한다.
치은(잇몸)과 치아 사이에는 V자 모양의 틈이 있는데, 이 홈(sulcus)의 잇몸 선 아래 부분을 박테리아가 공격하여 치주인대와 인접조직을 손상시키는 것이 치주질환이다. 염증이 진행되어 더 많은 조직이 손상되면서 홈이 치주낭(periodontal pocket)으로 발전하게 되며, 치주염이 심할수록 치주낭의 깊이가 깊어지게 된다. 치주낭이 깊어지면서 치주인대에 염증이 생기게 되고 골소실이 일어나게 되는 것이 치주질환이다.
치주질환의 직접적인 원인은 치아에 지속적으로 형성되는 플라크(plaque)라는 세균막이 원인이다. 플라크는 끈적끈적하고 무색이며, 이것이 제거되지 않고 단단해지면 치석이 된다. 플라크와 치석이 쌓이면 잇몸이 치아로부터 떨어지고, 이로 인해 틈이 벌어지면서 치아와 잇몸 사이에 치주낭이 형성된다. 치주낭이 발생하게 되면 세균이 더욱더 빠른 속도로 증식이 되며, 결국에는 치아를 둘러싸고 있는 치조골이 파괴되면서 치주염이 발생하게 된다.
치주질환은 연령과도 관계가 깊은데 20세 이상의 성인의 경우에는 과반수에서, 35세 이후에는 4명당 3명꼴로, 그리고 40세 이상의 장노년층의 경우 80~90%에서 잇몸질환이 발생한다. 노년기로 접어들면 침이 잘 분비되지 않아 세균번식에 유리한 환경이 되면서 잇몸질환과 노인성 충치가 더욱 심해진다. 치주염은 천천히 진행이 되기 때문에 질환을 인지하기에는 오랜 시간이 걸리기도 하며, 오랜 기간 동안 방치되어 있는 만큼 노인성 질환으로도 많이 불리고 있다. 또한, 노년기에는 잇몸이 점차 내려앉게 돼 치아뿌리가 노출되고 그로 인해 치근우식증(치아뿌리에 충치가 생기는 것)이 생길 수 있는데, 실제로 60세 이상 노인의 70% 가량이 치근우식증을 앓는 것으로 확인되고 있다.
하지만 치주질환도 조기 진단 및 치료를 통해 진행을 중지하거나, 이미 손상 받은 치아주위 조직도 조직재생치료를 통해 회복할 수 있다.
현재 치주질환의 진단은 환자의 자각증상, 방사선 촬영 후 치주낭 탐침기를 이용하여 치주낭 깊이, 잇몸의 퇴측 정도를 측정하여 치주염 진행 정도를 파악하거나, 세균감염 정도를 분석하는 것에 의존하고 있다. 하지만 치주질환의 효과적인 치료를 위해서는 조기 진단 및/또는 간편한 검사가 가능한 치주질환 진단 인자에 대한 개발이 필요하나 미비한 실정이다.
이에, 본 발명자들은 치주염의 염증관련 질환 진단을 위한 신뢰성 높은 바이오마커를 개발하던 중, 감염된 젊은 또는 노화된 구강세포에서 고발현되는 유전자군을 확인하고 본 발명을 완성하였다.
본 발명은 치주염 진단용 조성물을 제공하는 것을 목적으로 한다.
또한, 본 발명은 치주염 진단을 위한 정보제공방법을 제공하는 것을 목적으로 한다.
또한, 본 발명은 치주염 치료제의 스크리닝 방법을 제공하는 것을 목적으로 한다.
1. PTX3(pentraxin 3), CXCL1(chemokine(C-X-C motif) ligand 1), CXCL2(chemokine(C-X-C motif) ligand 2), TNFAIP2(TNF alpha induced protein 2), IL8(interleukin 8), IL6(interleukin 6), NFKB1(nuclear factor of kappa light polpeptide gene enhancer in B-cells 1), G0S2(G0/G1 switch 2), ICM1(intercellular adhesion molecule 1), ICM2(intercellular adhesion molecule 2), ICM3(intercellular adhesion molecule 3), PTGES(prostaglandin E synthase), PMAIP1(phorbol-12-myristate-13-acetate-induced protein 1), SMOX(spermine oxidase), TNFAIP6(TNF alpha induced protein 6), MMP(matrix metallopeptidase 3), IFIT3(interferon induced protein with tetratricopeptide repeats 3), CXCL6(chemokine(C-X-C motif) ligand 6), BIRC3(baculoviral IAP repeat containing 3), BCL2A1(BCL2-related protein A1), GCH1(GTP cyclohydrolase 1), BMP2(bone morphogenetic protein 2), CH25H(cholesterol 25-hydroxylase), TSLP(thymie stromal lymphopoietin), IFIT2(interferon induced protein with tetratricopeptide repeats 2), HUNK(hormonally upregulated Neu-associated kinase), GADD45B(growth arrest and DNA damage inducible beta), KLF10(kruppel-like factor 10), ID1(inhibitor of DNA binding 1), TM4SF1(transmembrane 4 L six family member 1) 및 CSRNP1(cysteine-serine-rich nuclear protein 1) 유전자로 이루어진 군으로부터 선택되는 어느 하나 이상의 유전자의 mRNA 또는 상기 유전자가 코딩하는 단백질 수준을 측정하는 제제를 포함하는 치주염 진단용 조성물.
2. 위 1에 있어서, 상기 유전자 중 GADD45B(growth arrest and DNA damage inducible beta), KLF10(kruppel-like factor 10), ID1(inhibitor of DNA binding 1), TM4SF1(transmembrane 4 L six family member 1) 및 CSRNP1(cysteine-serine-rich nuclear protein 1) 유전자로 이루어진 군으로부터 선택되는 어느 하나 이상의 유전자의 mRNA 또는 상기 유전자가 코딩하는 단백질 수준을 측정하는 제제를 포함하고, 상기 치주염은 노인성 치주염인, 조성물.
3. 위 1 또는 2의 조성물을 포함하는 치주염 진단용 키트.
4. 생물학적 시료에 존재하는 PTX3(pentraxin 3), CXCL1(chemokine(C-X-C motif) ligand 1), CXCL2(chemokine(C-X-C motif) ligand 2), TNFAIP2(TNF alpha induced protein 2), IL8(interleukin8), IL6(interleukin 6), NFKB1(nuclear factor of kappa light polpeptide gene enhancer in B-cells 1), G0S2(G0/G1 switch 2), ICM1(intercellular adhesion molecule 1), ICM2(intercellular adhesion molecule 2), ICM3(intercellular adhesion molecule 3), PTGES(prostaglandin E synthase), PMAIP1(phorbol-12-myristate-13-acetate-induced protein 1), SMOX(spermine oxidase), TNFAIP6(TNF alpha induced protein 6), MMP(matrix metallopeptidase 3), IFIT3(interferon induced protein with tetratricopeptide repeats 3), CXCL6(chemokine(C-X-C motif) ligand 6), BIRC3(baculoviral IAP repeat containing 3), BCL2A1(BCL2-related protein A1), GCH1(GTP cyclohydrolase 1), BMP2(bone morphogenetic protein 2), CH25H(cholesterol 25-hydroxylase), TSLP(thymie stromal lymphopoietin), IFIT2(interferon induced protein with tetratricopeptide repeats 2), HUNK(hormonally upregulated Neu-associated kinase), GADD45B(growth arrest and DNA damage inducible beta), KLF10(kruppel-like factor 10), ID1(inhibitor of DNA binding 1), TM4SF1(transmembrane 4 L six family member 1) 및 CSRNP1(cysteine-serine-rich nuclear protein 1) 유전자로 이루어진 군으로부터 선택되는 어느 하나 이상의 유전자의 mRNA 또는 상기 유전자가 코딩하는 단백질의 발현 수준을 측정하는 단계; 및 상기 측정된 발현 수준을 정상 대조군의 발현 수준과 비교하는 단계를 포함하는, 치주염 진단을 위한 정보제공방법.
5. 위 4에 있어서, 생물학적 시료에 존재하는 상기 유전자 중 GADD45B(growth arrest and DNA damage inducible beta), KLF10(kruppel-like factor 10), ID1(inhibitor of DNA binding 1), TM4SF1(transmembrane 4 L six family member 1) 및 CSRNP1(cysteine-serine-rich nuclear protein 1) 유전자로 이루어진 군으로부터 선택되는 어느 하나 이상의 유전자의 mRNA 또는 상기 유전자가 코딩하는 단백질의 발현 수준을 측정하는 단계; 및 상기 측정된 발현 수준을 정상 대조군의 발현 수준과 비교하는 단계를 포함하고, 상기 치주염은 노인성 치주염인, 방법.
6. 위 4 또는 5에 있어서, 상기 생물학적 시료는 조직, 세포, 혈액, 혈청, 혈장, 타액 및 뇨로 이루어진 군으로부터 선택되는 것인, 방법.
7. 개체 내 PTX3(pentraxin 3), CXCL1(chemokine(C-X-C motif) ligand 1), CXCL2(chemokine(C-X-C motif) ligand 2), TNFAIP2(TNF alpha induced protein 2), IL8(interleukin 8), IL6(interleukin 6), NFKB1(nuclear factor of kappa light polpeptide gene enhancer in B-cells 1), G0S2(G0/G1 switch 2), ICM1(intercellular adhesion molecule 1), ICM2(intercellular adhesion molecule 2), ICM3(intercellular adhesion molecule 3), PTGES(prostaglandin E synthase), PMAIP1(phorbol-12-myristate-13-acetate-induced protein 1), SMOX(spermine oxidase), TNFAIP6(TNF alpha induced protein 6), MMP(matrix metallopeptidase 3), IFIT3(interferon induced protein with tetratricopeptide repeats 3), CXCL6(chemokine(C-X-C motif) ligand 6), BIRC3(baculoviral IAP repeat containing 3), BCL2A1(BCL2-related protein A1), GCH1(GTP cyclohydrolase 1), BMP2(bone morphogenetic protein 2), CH25H(cholesterol 25-hydroxylase), TSLP(thymie stromal lymphopoietin), IFIT2(interferon induced protein with tetratricopeptide repeats 2), HUNK(hormonally upregulated Neu-associated kinase), GADD45B(growth arrest and DNA damage inducible beta), KLF10(kruppel-like factor 10), ID1(inhibitor of DNA binding 1), TM4SF1(transmembrane 4 L six family member 1) 및 CSRNP1(cysteine-serine-rich nuclear protein 1) 유전자로 이루어진 군으로부터 선택되는 어느 하나 이상의 유전자의 mRNA 또는 상기 유전자가 코딩하는 단백질의 발현 수준을 감소시키는 물질을 선별하는 단계를 포함하는 치주염 치료제의 스크리닝 방법.
8. 위 7에 있어서, 개체 내 상기 유전자 중 GADD45B(growth arrest and DNA damage inducible beta), KLF10(kruppel-like factor 10), ID1(inhibitor of DNA binding 1), TM4SF1(transmembrane 4 L six family member 1) 및 CSRNP1(cysteine-serine-rich nuclear protein 1) 유전자로 이루어진 군으로부터 선택되는 어느 하나 이상의 유전자의 mRNA 또는 상기 유전자가 코딩하는 단백질의 발현 수준을 감소시키는 물질을 선별하는 단계를 포함하고, 상기 치주염은 노인성 치주염인, 방법.
본 발명은 노인성 치주질환 진단용 조성물에 관한 것으로, 본 발명의 조성물은 노인성 치주염의 염증관련 질환의 예방을 위한 진단 및 약물 반응 진단, 치료용 물질의 타겟 및 치료 물질 개발 스크리닝을 위한 바이오마커로써 유용하게 활용될 수 있을 것으로 기대된다.
도 1은 본 발명의 일 실시예에 따른 RNA-seq 분석 파이프라인을 나타낸 도이다.
도 2는 본 발명의 일 실시예에 따른 RNA-Seq 데이터의 분포를 나타낸 것으로, (A) 비감염 GF(P4) vs. 비감염 GF(P22), (B) 비감염 GF(P4) vs. F. n-감염 GF(P4), (C) 비감염 GF(P22) vs. F. n-감염 GF(P22), 및 (D) F. n-감염 GF(P4) vs. F. n-감염 GF(P22)를 Spearman 순위 상관 계수로 표시한 도이다.
도 3은 본 발명의 일 실시예에 따른 RNA-seq 데이터 분석 전략을 나타낸 것으로, (A) 인간 게놈으로 매핑된 DEGs 수, 및 (B) F. n 게놈으로 매핑된 RNA-seq 데이터를 표시한 도이다.
도 4는 본 발명의 일 실시예에 따라 유전자 발현 분석의 히트맵(Heat map)을 나타낸 것으로, (A) 비감염 GF(P4) vs. F. n-감염 GF(P4) 사이의 DEGs, (B) 비감염 GF(P22) vs. F. n-감염 GF(P22) 사이의 DEGs, 및 (C) F. n-감염 GF(P4) vs. F. n-감염 GF(P22) 사이의 DEGs의 히트맵을 나타낸 도이다. 이때, Benjamini-Hochberg 다중 검사 조정으로 q<0.05를 얻은 경우 유전자는 유의미하게 차별화된 것으로 간주되었다.
도 5는 본 발명의 일 실시예에 따른 거짓 발견률(FDR) < 5 %인 DEG의 중첩을 나타낸 벤다이어그램으로, (A) 감염에 대한 젊은 GF-특이적 반응, (B) 노화된 GF-특이적 반응, 및 (C) 젊은 GF 및 노화된 GF의 공통적인 유전자를 나타낸 도이다.
도 6은 본 발명의 일 실시예에 따라 DEG의 히트맵(Heat map)을 나타낸 것으로, (A) F. n-감염에 대한 젊은 GF-특이적 반응 유전자 히트맵, (B) F. n-감염에 대한 노화된 GF-특이적 반응 유전자 히트맵, 및 (C) F 감염에 대한 젊은 GF 및 노화된 GF의 공통 유전자 히트맵을 나타낸 도이다.
도 7은 본 발명의 일 실시예에 따라 감염에 대해 (A) 젊은 GF-특이적 반응하는 유전자, 및 (B) 노화된 GF-특이적 반응하는 유전자의 DEG IPA 네트워크 분석에서 IPA에 의해 예측된 네트워크를 나타낸 도이다.
도 8은 본 발명의 일 실시예에 따라 감염에 대해 (A) 젊은 GF-특이적 반응하는 유전자, 및 (B) 노화된 GF-특이적 반응하는 유전자의 DEG IPA 네트워크 분석에서 IPA에 의해 예측된 네트워크를 세포내 유전자발현 위치에 따라 나타낸 도이다.
도 2는 본 발명의 일 실시예에 따른 RNA-Seq 데이터의 분포를 나타낸 것으로, (A) 비감염 GF(P4) vs. 비감염 GF(P22), (B) 비감염 GF(P4) vs. F. n-감염 GF(P4), (C) 비감염 GF(P22) vs. F. n-감염 GF(P22), 및 (D) F. n-감염 GF(P4) vs. F. n-감염 GF(P22)를 Spearman 순위 상관 계수로 표시한 도이다.
도 3은 본 발명의 일 실시예에 따른 RNA-seq 데이터 분석 전략을 나타낸 것으로, (A) 인간 게놈으로 매핑된 DEGs 수, 및 (B) F. n 게놈으로 매핑된 RNA-seq 데이터를 표시한 도이다.
도 4는 본 발명의 일 실시예에 따라 유전자 발현 분석의 히트맵(Heat map)을 나타낸 것으로, (A) 비감염 GF(P4) vs. F. n-감염 GF(P4) 사이의 DEGs, (B) 비감염 GF(P22) vs. F. n-감염 GF(P22) 사이의 DEGs, 및 (C) F. n-감염 GF(P4) vs. F. n-감염 GF(P22) 사이의 DEGs의 히트맵을 나타낸 도이다. 이때, Benjamini-Hochberg 다중 검사 조정으로 q<0.05를 얻은 경우 유전자는 유의미하게 차별화된 것으로 간주되었다.
도 5는 본 발명의 일 실시예에 따른 거짓 발견률(FDR) < 5 %인 DEG의 중첩을 나타낸 벤다이어그램으로, (A) 감염에 대한 젊은 GF-특이적 반응, (B) 노화된 GF-특이적 반응, 및 (C) 젊은 GF 및 노화된 GF의 공통적인 유전자를 나타낸 도이다.
도 6은 본 발명의 일 실시예에 따라 DEG의 히트맵(Heat map)을 나타낸 것으로, (A) F. n-감염에 대한 젊은 GF-특이적 반응 유전자 히트맵, (B) F. n-감염에 대한 노화된 GF-특이적 반응 유전자 히트맵, 및 (C) F 감염에 대한 젊은 GF 및 노화된 GF의 공통 유전자 히트맵을 나타낸 도이다.
도 7은 본 발명의 일 실시예에 따라 감염에 대해 (A) 젊은 GF-특이적 반응하는 유전자, 및 (B) 노화된 GF-특이적 반응하는 유전자의 DEG IPA 네트워크 분석에서 IPA에 의해 예측된 네트워크를 나타낸 도이다.
도 8은 본 발명의 일 실시예에 따라 감염에 대해 (A) 젊은 GF-특이적 반응하는 유전자, 및 (B) 노화된 GF-특이적 반응하는 유전자의 DEG IPA 네트워크 분석에서 IPA에 의해 예측된 네트워크를 세포내 유전자발현 위치에 따라 나타낸 도이다.
이하 본 발명을 상세히 설명한다.
본 발명은 PTX3(pentraxin 3), CXCL1(chemokine(C-X-C motif) ligand 1), CXCL2(chemokine(C-X-C motif) ligand 2), TNFAIP2(TNF alpha induced protein 2), IL8(interleukin 8), IL6(interleukin 6), NFKB1(nuclear factor of kappa light polpeptide gene enhancer in B-cells 1), G0S2(G0/G1 switch 2), ICM1(intercellular adhesion molecule 1), ICM2(intercellular adhesion molecule 2), ICM3(intercellular adhesion molecule 3), PTGES(prostaglandin E synthase), PMAIP1(phorbol-12-myristate-13-acetate-induced protein 1), SMOX(spermine oxidase), TNFAIP6(TNF alpha induced protein 6), MMP(matrix metallopeptidase 3), IFIT3(interferon induced protein with tetratricopeptide repeats 3), CXCL6(chemokine(C-X-C motif) ligand 6), BIRC3(baculoviral IAP repeat containing 3), BCL2A1(BCL2-related protein A1), GCH1(GTP cyclohydrolase 1), BMP2(bone morphogenetic protein 2), CH25H(cholesterol 25-hydroxylase), TSLP(thymie stromal lymphopoietin), IFIT2(interferon induced protein with tetratricopeptide repeats 2), HUNK(hormonally upregulated Neu-associated kinase), GADD45B(growth arrest and DNA damage inducible beta), KLF10(kruppel-like factor 10), ID1(inhibitor of DNA binding 1), TM4SF1(transmembrane 4 L six family member 1) 및 CSRNP1(cysteine-serine-rich nuclear protein 1) 유전자로 이루어진 군으로부터 선택되는 어느 하나 이상의 유전자의 mRNA 또는 상기 유전자가 코딩하는 단백질 수준을 측정하는 제제를 포함하는 치주염 진단용 조성물을 제공한다.
본 발명은 PTX3, CXCL1, CXCL2, TNFAIP2, IL8, IL6, NFKB1, G0S2, ICM1, ICM2, ICM3, PTGES, PMAIP1, SMOX, TNFAIP6, MMP, IFIT3, CXCL6, BIRC3, BCL2A1, GCH1, BMP2, CH25H, TSLP, IFIT2, HUNK, GADD45B, KLF10, ID1, TM4SF1 및/또는 CSRNP1유전자의 mRNA 또는 상기 유전자가 코딩하는 단백질의 발현 정도를 확인함으로써 치주염 발병 여부를 진단할 수 있다. 구체적으로, 본 발명자들은 PTX3, CXCL1, CXCL2, TNFAIP2, IL8, IL6, NFKB1, G0S2, ICM1, ICM2, ICM3, PTGES, PMAIP1, SMOX, TNFAIP6, MMP, IFIT3, CXCL6, BIRC3, BCL2A1, GCH1, BMP2, CH25H, TSLP, IFIT2, HUNK, GADD45B, KLF10, ID1, TM4SF1 및/또는 CSRNP1 유전자의 발현 수준과 구강 미생물 감염이 비례하는 것을 확인한 것으로, 본 발명의 조성물은 PTX3, CXCL1, CXCL2, TNFAIP2, IL8, IL6, NFKB1, G0S2, ICM1, ICM2, ICM3, PTGES, PMAIP1, SMOX, TNFAIP6, MMP, IFIT3, CXCL6, BIRC3, BCL2A1, GCH1, BMP2, CH25H, TSLP, IFIT2, HUNK, GADD45B, KLF10, ID1, TM4SF1 및 CSRNP1 유전자로 이루어진 군으로부터 선택되는 어느 하나 이상의 유전자의 mRNA 또는 상기 유전자가 코딩하는 단백질 수준을 측정하여, 그 발현 수준에 따라 치주염 발병 여부를 진단할 수 있다.
PTX3, CXCL1, CXCL2, TNFAIP2, IL8, IL6, NFKB1, G0S2, ICM1, ICM2, ICM3, PTGES, PMAIP1, SMOX, TNFAIP6, MMP, IFIT3, CXCL6, BIRC3, BCL2A1, GCH1, BMP2, CH25H, TSLP, IFIT2, HUNK, GADD45B, KLF10, ID1, TM4SF1 또는 CSRNP1 유전자는 PTX3, CXCL1, CXCL2, TNFAIP2, IL8, IL6, NFKB1, G0S2, ICM1, ICM2, ICM3, PTGES, PMAIP1, SMOX, TNFAIP6, MMP, IFIT3, CXCL6, BIRC3, BCL2A1, GCH1, BMP2, CH25H, TSLP, IFIT2, HUNK, GADD45B, KLF10, ID1, TM4SF1 또는 CSRNP1 단백질을 암호화하는 게놈 DNA와 cDNA를 모두 포함한다. 상기 유전자는 치주염을 진단하기 위한 개체에 따라 뉴클레오티드 서열이 상이할 수 있으며, "개체"란 치주염이거나 치주염이 진행될 수 있는 인간을 포함한 쥐, 생쥐, 가축 등의 모든 동물을 의미한다. 구체적인 예로, 인간을 포함한 포유동물일 수 있다.
인간인 경우 예를 들면 PTX3, CXCL1, CXCL2, TNFAIP2, IL8, IL6, NFKB1, G0S2, ICM1, ICM2, ICM3, PTGES, PMAIP1, SMOX, TNFAIP6, MMP, IFIT3, CXCL6, BIRC3, BCL2A1, GCH1, BMP2, CH25H, TSLP, IFIT2, HUNK, GADD45B, KLF10, ID1, TM4SF1 및 CSRNP1 유전자는 순서대로 서열번호 1 내지 31의 뉴클레오티드 서열일 수 있으며, 상기 유전자가 코딩하는 단백질은 순서대로 서열번호 32 내지 62의 아미노산 서열일 수 있다.
본 발명의 진단 대상 질병인 "치주염(periodontitis)"은 치주조직에 염증이 발생한 것을 의미하며, 특히, 염증이 잇몸(즉, 연조직)에만 국한된 것 이 아니라 잇몸뼈 주변까지 진행된 경우를 치주염이라고 한다.
본 발명은 상기 유전자 중 GADD45B, KLF10, ID1, TM4SF1 및 CSRNP1 유전자로 이루어진 군으로부터 선택되는 어느 하나 이상의 유전자의 mRNA 또는 상기 유전자가 코딩하는 단백질 수준을 측정하는 제제를 포함하는 노인성 치주염 진단용 조성물을 제공한다.
본 발명은 GADD45B, KLF10, ID1, TM4SF1 및 CSRNP1 유전자로 이루어진 군으로부터 선택되는 어느 하나 이상의 유전자의 mRNA 또는 상기 유전자가 코딩하는 단백질의 발현 정도를 확인함으로써 노인성 치주염 발병 여부를 진단할 수 있다. 구체적으로, 본 발명자들은 특히 노화된 구강세포에서 GADD45B, KLF10, ID1, TM4SF1 및/또는 CSRNP1 유전자의 발현 수준과 구강 미생물 감염이 비례하는 것을 확인한 것으로, 본 발명의 조성물은 GADD45B, KLF10, ID1, TM4SF1 및 CSRNP1 유전자로 이루어진 군으로부터 선택되는 어느 하나 이상의 유전자의 mRNA 또는 상기 유전자가 코딩하는 단백질 수준을 측정하여, 그 발현 수준에 따라 노인성 치주염 발병 여부를 진단할 수 있다.
GADD45B, KLF10, ID1, TM4SF1 또는 CSRNP1 유전자는 GADD45B, KLF10, ID1, TM4SF1 또는 CSRNP1 단백질을 암호화하는 게놈 DNA와 cDNA를 모두 포함한다. 상기 유전자는 노인성 치주염을 진단하기 위한 개체에 따라 뉴클레오티드 서열이 상이할 수 있으며, "개체"란 치주염이거나 치주염이 진행될 수 있는 인간을 포함한 쥐, 생쥐, 가축 등의 모든 동물을 의미한다. 구체적인 예로, 인간을 포함한 포유동물일 수 있다.
본 발명의 진단 대상 질병인 "노인성 치주염"은 노화에 따라 미생물의 감염과 그에 따른 염증 정도가 심각해지며, 결국 치아를 둘러싸고 있는 치조골이 파괴되면서 치주염이 발생한 것을 의미한다.
본 발명에서 "진단"이란 넓은 의미로는 환자의 병의 실태를 모든 면에 걸쳐서 판단하는 것을 의미한다. 판단의 내용은 병명, 병인, 병형, 경중, 병상의 상세한 양태, 합병증의 유무, 및 예후 등이다. 본 발명에서 진단은 치주염의 발병 여부 및 치주염 수준 등을 판단하는 것이다.
상기 mRNA 수준을 측정하는 제제는 mRNA에 상보적으로 결합하는 센스 및 안티센스 프라이머, 또는 프로브일 수 있으나, 이에 제한되는 것은 아니다.
본 발명에서 "프라이머"란 DNA 합성의 기시점이 되는 짧은 유전자 서열로써, 진단, DNA 시퀀싱 등에 이용할 목적으로 합성된 올리고뉴클레오티드를 의미한다. 상기 프라이머들은 통상적으로 15 내지 30 염기쌍의 길이로 합성하여 사용할 수 있으나, 사용 목적에 따라 달라질 수 있으며, 공지된 방법으로 메틸화, 캡화 등으로 변형시킬 수 있다.
본 발명에서 "프로브"란 효소 화학적인 분리정제 또는 합성과정을 거쳐 제작된 수 염기 내지 수백 염기길이의 mRNA와 특이적으로 결합할 수 있는 핵산을 의미한다. 방사성 동위원소나 효소 등을 표지하여 mRNA의 존재 유무를 확인할 수 있으며, 공지된 방법으로 디자인하고 변형시켜 사용할 수 있다.
상기 단백질 수준을 측정하는 제제는 유전자가 코딩하는 단백질에 특이적으로 결합하는 항체일 수 있으나, 이에 제한되는 것은 아니다.
본 발명에서 "항체"는 면역학적으로 특정 항원과 반응성을 갖는 면역글로불린 분자를 포함하며, 단클론(monoclonal) 항체 및 다클론(polyclonal) 항체를 모두 포함한다. 또한, 상기 항체는 키메라성 항체(예를 들면, 인간화 뮤린 항체) 및 이종결합항체(예를 들면, 양특이성 항체)와 같은 유전공학에 의해 생산된 형태를 포함한다. 단클론항체는 하이브리도마 세포를 이용한 방법, 또는 파지 항체 라이브러리 기술을 이용하여 제조할 수 있으며, 상기 과정에 필요한 기술은 당업계에 잘 알려져 있어 용이하게 실시할 수 있다. 다클론항체는 단백질 항원을 적합한 동물에게 주사하고, 이 동물로부터 항혈청을 수집한 다음, 공지의 친화성(affinity) 기술을 이용하여 항혈청으로부터 항체를 분리하여 얻을 수 있다.
또한, 본 발명은 상기 조성물을 포함하는 노인성 치주염 진단용 키트를 제공한다.
본 발명의 진단용 키트는 분석 방법에 적합한 한 종류 또는 그 이상의 다른 구성성분 조성물, 용액 또는 장치로 구성된다.
예컨대, 본 발명의 키트는 PCR을 수행하기 위해, 분석하고자 하는 시료로부터 유래된 게놈 DNA, 본 발명의 마커 유전자에 대해 특이적인 프라이머 세트, 적당량의 DNA 중합 효소, dNTP 혼합물, PCR 완충용액 및 물을 포함하는 키트일 수 있다. 상기 PCR 완충용액은 KCl, Tris-HCl 및 MgCl2를 함유할 수 있다. 이외에 PCR산물의 증폭 여부를 확인할 수 있는 전기영동 수행에 필요한 구성 성분들이 본 발명의 키트에 추가로 포함될 수 있다.
또한, 본 발명의 키트는 RT-PCR을 수행하기 위해 필요한 필수 요소를 포함하는 키트일 수 있다. RT-PCR키트는 마커 유전자에 대한 특이적인 각각의 프라이머 쌍 외에도 테스트 튜브 또는 다른 적절한 컨테이너, 반응 완충액, 데옥시뉴클레오티드(dNTPs), Taq-폴리머레이즈 및 역전사 효소와 같은 효소, DNase, RNase 억제제, DEPC-수(DEPC-water), 멸균수 등을 포함할 수 있다. 또한 정량 대조군으로 사용되는 유전자에 특이적인 프라이머 쌍을 포함할 수 있다.
또한, 본 발명의 키트는 DNA 칩을 수행하기 위해 필요한 필수 요소를 포함하는 키트일 수 있다. DNA 칩 키트는, 유전자 또는 그의 단편에 해당하는 cDNA가 프로브로 부착되어 있는 기판을 포함하고, 기판은 정량구조 유전자 또는 그의 단편에 해당하는 cDNA를 포함할 수 있다. 또한, 본 발명의 키트는 본 발명의 마커 유전자가 고정화되어 있는 기판을 갖는 마이크로어레이 형태일 수 있다. 또한, 본 발명의 키트는 ELISA를 수행하기 위해 필요한 필수 요소를 포함하는 것을 특징으로 하는 키트일 수 있다. ELISA 키트는 마커 단백질에 대한 특이적인 항체를 포함하며, 상기 단백질 수준을 측정하는 제제를 포함한다. 상기 ELISA 키트는 항원-항체 복합체를 형성한 항체를 검출할 수 있는 시약, 예를 들면 표지된 2차 항체, 발색단(chromopores), 효소, 및 그의 기질을 포함할 수 있다. 또한, 정량 대조군 단백질에 특이적인 항체를 포함할 수 있다.
본 발명에서 "항원-항체 복합체"란 유전자가 코딩하는 단백질과 이에 특이적인 항체의 결합물을 의미한다. 항원-항체 복합체의 형성량은 검출 라벨(detection label)의 시그널의 크기를 통해서 정량적으로 측정할 수 있다. 이러한 검출 라벨은 효소, 형광물, 리간드, 발광물, 미세입자(microparticle), 레독스 분자 및 방사선 동위원소로 이루어진 그룹 중에서 선택할 수 있으며, 이에 제한되는 것은 아니다.
또한, 본 발명은 생물학적 시료에 존재하는 PTX3(pentraxin 3), CXCL1(chemokine(C-X-C motif) ligand 1), CXCL2(chemokine(C-X-C motif) ligand 2), TNFAIP2(TNF alpha induced protein 2), IL8(interleukin 8), IL6(interleukin 6), NFKB1(nuclear factor of kappa light polpeptide gene enhancer in B-cells 1), G0S2(G0/G1 switch 2), ICM1(intercellular adhesion molecule 1), ICM2(intercellular adhesion molecule 2), ICM3(intercellular adhesion molecule 3), PTGES(prostaglandin E synthase), PMAIP1(phorbol-12-myristate-13-acetate-induced protein 1), SMOX(spermine oxidase), TNFAIP6(TNF alpha induced protein 6), MMP(matrix metallopeptidase 3), IFIT3(interferon induced protein with tetratricopeptide repeats 3), CXCL6(chemokine(C-X-C motif) ligand 6), BIRC3(baculoviral IAP repeat containing 3), BCL2A1(BCL2-related protein A1), GCH1(GTP cyclohydrolase 1), BMP2(bone morphogenetic protein 2), CH25H(cholesterol 25-hydroxylase), TSLP(thymie stromal lymphopoietin), IFIT2(interferon induced protein with tetratricopeptide repeats 2), HUNK(hormonally upregulated Neu-associated kinase), GADD45B(growth arrest and DNA damage inducible beta), KLF10(kruppel-like factor 10), ID1(inhibitor of DNA binding 1), TM4SF1(transmembrane 4 L six family member 1) 및 CSRNP1(cysteine-serine-rich nuclear protein 1) 유전자로 이루어진 군으로부터 선택되는 어느 하나 이상의 유전자의 mRNA 또는 상기 유전자가 코딩하는 단백질의 발현 수준을 측정하는 단계; 및 상기 측정된 발현 수준을 정상 대조군의 발현 수준과 비교하는 단계를 포함하는, 치주염 진단을 위한 정보제공방법을 제공한다.
본 발명자들은 PTX3, CXCL1, CXCL2, TNFAIP2, IL8, IL6, NFKB1, G0S2, ICM1, ICM2, ICM3, PTGES, PMAIP1, SMOX, TNFAIP6, MMP, IFIT3, CXCL6, BIRC3, BCL2A1, GCH1, BMP2, CH25H, TSLP, IFIT2, HUNK, GADD45B, KLF10, ID1, TM4SF1 및/또는 CSRNP1 유전자의 발현 수준과 구강 미생물 감염이 비례하는 것을 확인한 것으로, 본 발명의 방법은 개체로부터 얻어진 생물학적 시료의 PTX3, CXCL1, CXCL2, TNFAIP2, IL8, IL6, NFKB1, G0S2, ICM1, ICM2, ICM3, PTGES, PMAIP1, SMOX, TNFAIP6, MMP, IFIT3, CXCL6, BIRC3, BCL2A1, GCH1, BMP2, CH25H, TSLP, IFIT2, HUNK, GADD45B, KLF10, ID1, TM4SF1 및 CSRNP1 유전자로 이루어진 군으로부터 선택되는 어느 하나 이상의 유전자의 mRNA 또는 상기 유전자가 코딩하는 단백질 수준을 측정하여 이를 정상 대조군과 비교함으로써, 해당 개체의 치주염 발병 여부를 진단하기 위한 정보를 제공할 수 있다.
본 발명은 상기 유전자 중 생물학적 시료에 존재하는 GADD45B(growth arrest and DNA damage inducible beta), KLF10(kruppel-like factor 10), ID1(inhibitor of DNA binding 1), TM4SF1(transmembrane 4 L six family member 1) 및 CSRNP1(cysteine-serine-rich nuclear protein 1) 유전자로 이루어진 군으로부터 선택되는 어느 하나 이상의 유전자의 mRNA 또는 상기 유전자가 코딩하는 단백질의 발현 수준을 측정하는 단계; 및 상기 측정된 발현 수준을 정상 대조군의 발현 수준과 비교하는 단계를 포함하는, 노인성 치주염 진단을 위한 정보제공방법을 제공한다.
본 발명자들은 특히 노화된 구강세포에서 GADD45B, KLF10, ID1, TM4SF1 및/또는 CSRNP1 유전자의 발현 수준과 구강 미생물 감염이 비례하는 것을 확인한 것으로, 본 발명의 방법은 개체로부터 얻어진 생물학적 시료의 GADD45B, KLF10, ID1, TM4SF1 및 CSRNP1 유전자로 이루어진 군으로부터 선택되는 어느 하나 이상의 유전자의 mRNA 또는 상기 유전자가 코딩하는 단백질 수준을 측정하여 이를 정상 대조군과 비교함으로써, 해당 개체의 노인성 치주염 발병 여부를 진단하기 위한 정보를 제공할 수 있다.
상기 생물학적 시료는 조직, 세포, 혈액, 혈청, 혈장, 타액 및 등을 포함할 수 있고, 보다 바람직하게는 혈액일 수 있으며, 더욱 바람직하게는 혈액 내 말초혈액단핵세포일 수 있으나, 이것으로 제한되는 것은 아니다.
상기 mRNA의 발현 수준을 측정하기 위한 방법은 중합효소반응(PCR), 역전사 중합효소반응(RT-PCR), 경쟁적 역전사 중합효소반응(Competitive RT-PCR), 실시간 역전사 중합효소반응(Realtime RT-PCR), RNase 보호 분석법(RPA;RNase protection assay), 노던 블랏팅(Northern blotting) 및 DNA 칩으로 이루어진 군으로부터 선택되는 1종 이상의 방법을 통해 측정될 수 있으나, 이에 제한되지 않는다.
상기 단백질의 발현 수준을 측정하기 위한 방법은 웨스턴 블롯, ELISA(enzyme linked immunosorbent assay), 방사선면역분석(RIA: Radioimmunoassay), 방사 면역 확산법(radioimmunodiffusion), 오우크테로니(Ouchterlony) 면역확산법, 로케트(rocket) 면역전기영동, 조직 면역 염색, 면역침전 분석법(Immunoprecipitation Assay), 보체 고정 분석법(Complement Fixation Assay), 유세포분석(Fluorescence Activated Cell Sorter, FACS) 및 단백질 칩(protein chip)으로 이루어진 군으로부터 선택되는 1종 이상의 방법을 통해 측정될 수 있으나, 이에 제한되지 않는다.
본 발명에서 "진단을 위한 정보제공방법"은 진단을 위한 예비적 단계로써 치주염(또는 노인성 치주염)의 진단을 위하여 필요한 객관적인 기초정보를 제공하는 것이며 의사의 임상학적 판단 또는 소견은 제외된다.
또한, 본 발명은 개체 내 PTX3(pentraxin 3), CXCL1(chemokine(C-X-C motif) ligand 1), CXCL2(chemokine(C-X-C motif) ligand 2), TNFAIP2(TNF alpha induced protein 2), IL8(interleukin 8), IL6(interleukin 6), NFKB1(nuclear factor of kappa light polpeptide gene enhancer in B-cells 1), G0S2(G0/G1 switch 2), ICM1(intercellular adhesion molecule 1), ICM2(intercellular adhesion molecule 2), ICM3(intercellular adhesion molecule 3), PTGES(prostaglandin E synthase), PMAIP1(phorbol-12-myristate-13-acetate-induced protein 1), SMOX(spermine oxidase), TNFAIP6(TNF alpha induced protein 6), MMP(matrix metallopeptidase 3), IFIT3(interferon induced protein with tetratricopeptide repeats 3), CXCL6(chemokine(C-X-C motif) ligand 6), BIRC3(baculoviral IAP repeat containing 3), BCL2A1(BCL2-related protein A1), GCH1(GTP cyclohydrolase 1), BMP2(bone morphogenetic protein 2), CH25H(cholesterol 25-hydroxylase), TSLP(thymie stromal lymphopoietin), IFIT2(interferon induced protein with tetratricopeptide repeats 2), HUNK(hormonally upregulated Neu-associated kinase), GADD45B(growth arrest and DNA damage inducible beta), KLF10(kruppel-like factor 10), ID1(inhibitor of DNA binding 1), TM4SF1(transmembrane 4 L six family member 1) 및 CSRNP1(cysteine-serine-rich nuclear protein 1) 유전자로 이루어진 군으로부터 선택되는 어느 하나 이상의 유전자의 mRNA 또는 상기 유전자가 코딩하는 단백질의 발현 수준을 증가시키는 물질을 선별하는 단계를 포함하는 치주염 치료제의 스크리닝 방법을 제공한다.
본 발명자들은 PTX3, CXCL1, CXCL2, TNFAIP2, IL8, IL6, NFKB1, G0S2, ICM1, ICM2, ICM3, PTGES, PMAIP1, SMOX, TNFAIP6, MMP, IFIT3, CXCL6, BIRC3, BCL2A1, GCH1, BMP2, CH25H, TSLP, IFIT2, HUNK, GADD45B, KLF10, ID1, TM4SF1 및/또는 CSRNP1 유전자의 발현 수준과 구강 미생물 감염이 비례하는 것을 확인한 것으로, 대상 물질을 개체에 처리하여 개체의 PTX3, CXCL1, CXCL2, TNFAIP2, IL8, IL6, NFKB1, G0S2, ICM1, ICM2, ICM3, PTGES, PMAIP1, SMOX, TNFAIP6, MMP, IFIT3, CXCL6, BIRC3, BCL2A1, GCH1, BMP2, CH25H, TSLP, IFIT2, HUNK, GADD45B, KLF10, ID1, TM4SF1 및 CSRNP1 유전자로 이루어진 군으로부터 선택되는 어느 하나 이상의 유전자의 mRNA 또는 상기 유전자가 코딩하는 단백질 발현 수준이 감소한다면 치주염이 치료되는 것이므로, 그러한 물질을 치주염 치료제로 선별할 수 있다.
이는 개체에 대상 물질 처리 전에 개체 내 PTX3, CXCL1, CXCL2, TNFAIP2, IL8, IL6, NFKB1, G0S2, ICM1, ICM2, ICM3, PTGES, PMAIP1, SMOX, TNFAIP6, MMP, IFIT3, CXCL6, BIRC3, BCL2A1, GCH1, BMP2, CH25H, TSLP, IFIT2, HUNK, GADD45B, KLF10, ID1, TM4SF1 및 CSRNP1 유전자의 mRNA 또는 상기 유전자가 코딩하는 단백질의 발현 수준을 측정하고, 처리 후에 발현 수준을 측정하여 비교할 수도 있고, 여러 개체 중 일부 개체에 대상 물질을 처리하여 비교군과 상기 발현 수준을 비교할 수도 있다.
본 발명은 상기 유전자 중 개체 내 GADD45B(growth arrest and DNA damage inducible beta), KLF10(kruppel-like factor 10), ID1(inhibitor of DNA binding 1), TM4SF1(transmembrane 4 L six family member 1) 및 CSRNP1(cysteine-serine-rich nuclear protein 1) 유전자로 이루어진 군으로부터 선택되는 어느 하나 이상의 유전자의 mRNA 또는 상기 유전자가 코딩하는 단백질의 발현 수준을 증가시키는 물질을 선별하는 단계를 포함하는 노인성 치주염 치료제의 스크리닝 방법을 제공한다.
본 발명자들은 특히 노화된 구강세포에서 GADD45B, KLF10, ID1, TM4SF1 및/또는 CSRNP1 유전자의 발현 수준과 구강 미생물 감염이 비례하는 것을 확인한 것으로, 대상 물질을 개체에 처리하여 개체의 GADD45B, KLF10, ID1, TM4SF1 및/또는 CSRNP1 유전자로 이루어진 군으로부터 선택되는 어느 하나 이상의 유전자의 mRNA 또는 상기 유전자가 코딩하는 단백질 발현 수준이 감소한다면 노인성 치주염이 치료되는 것이므로, 그러한 물질을 노인성 치주염 치료제로 선별할 수 있다.
이는 개체에 대상 물질 처리 전에 개체 내 GADD45B, KLF10, ID1, TM4SF1 및/또는 CSRNP1 유전자의 mRNA 또는 상기 유전자가 코딩하는 단백질의 발현 수준을 측정하고, 처리 후에 발현 수준을 측정하여 비교할 수도 있고, 여러 개체 중 일부 개체에 대상 물질을 처리하여 비교군과 상기 발현 수준을 비교할 수도 있다.
개체에 대상 물질을 처리하는 방법은 특별히 한정되지 않으며, 예를 들면 개체로부터 얻어진 생물학적 시료에 처리할 수 있다. 생물학적 시료는 전술한 바의 시료일 수도 있고, 인간 구강세포일 수도 있다.
유전자 및 단백질의 발현 수준은 전술한 방법에 의해 측정할 수 있다.
본 발명의 스크리닝 방법에서 "대상 물질"은 본 발명의 mRNA 또는 단백질의 발현량에 영향을 미치는지 여부를 검사하기 위하여 스크리닝에서 이용되는 미지의 물질을 의미한다. 상기 대상물질은 화학물질, 뉴클레오타이드, 안티센스-RNA, siRNA(small interference RNA) 및 천연물 추출물을 포함하나, 이에 한정되는 것은 아니다.
이하, 본 발명을 구체적으로 설명하기 위해 실시예를 들어 상세하게 설명하기로 한다. 그러나 하기의 실시예는 본 발명을 보다 쉽게 이해하기 위하여 제공되는 것일 뿐, 하기 실시예에 의해 본 발명의 내용이 한정되는 것은 아니다.
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1. 세포 배양
본 실험은 전남대학교 치과병원 기관 검토위원회(승인번호 CNUDH-20 13-001)의 승인을 받았다. 실험의 성격 및 가능한 결과에 대해 설명한 후 모든 피험자로부터 서면 동의서를 받았다. 모든 피험자는 치주질환이 없는 성인이었다.
2. 세포 배양 및 시약
일차 인간 구강섬유아세포 (gingival fibroblasts, GF)는 이전에 공지된 방법으로 제조하였다(Ahn SH et al., NOX1/2 activation in human gingival fibroblasts by Fusobacterium nucleatum facilitates attachment of Porphyromonas gingivalis, Arch Microbiol, 2016:198(6):573-83. doi: 10.1007/s00203-016-1223-7, PubMed PMID: 27071620 참조). 인간 치은 조직은 전술한 바와 같이 전남대학교 IRB의 승인을 받아 수집하였다. GF는 10 % 열-불활성화 소태아혈청(PAA Laboratories, Etobicoke, Ontario, Canada), 100 U/mL 페니실린, 및 100 μg/mL 스트렙토마이신(Gibco BRL)이 보충된 Dulbecco's modified Eagle's 배지(DMEM; Gibco BRL, Grand Island, NY, US)에서 5 % CO2, 37 ℃ 조건으로 배양하였다. 0.25 % 트립신/0.02 % EDTA 용액(Sigma, MO, USA)을 사용하여 세포를 트립신화하고, 필요한 패시지(passage) 수에 도달할 때까지 1:3 비율로 계대배양하여 노화 현상을 관찰하였다.
하기 실험은 4 번째 계대(P4) 또는 22 번째 계대(P22)의 세포를 사용하였으며, 노화된 GF는 노화 관련 β-갈락토시다아제(SA-β-gal) 활성, 및 p53, p21 및 Cav-1과 같은 노화 마커의 발현으로 확인하였다.
3.
세균주
(Bacterial strains) 배양
F. nucleatum subsp . polymorphum(ATCC10953)을 37 ℃ 혐기성 챔버(85 % N2, 5 % CO2 및 10 % H2)에서 5 μg/mL hemin(Sigma, MO, USA)을 첨가한 TSB(tryptic soy broth)로 배양하였다. 박테리아를 원심분리(7,000xg, 10 분)하여 수집하고 인산염 완충 식염수로 세척한 후, 참고(reference) 표준에 대한 광학 밀도(OD)의 변경에 기초하여, 108 CFU/mL로 조정하였다. 박테리아는 1.5 % agar(Sigma), 5 % 멸균 탈섬유소 양 혈액, 5 μg/mL hemin, 및 1 μg/mL 메나디온(menadione)이 첨가된 TSB 배지에서 혐기 배양에 의해 계수되었다.
4. RNA 분리 및 시퀀싱
RNeasy Mini Kit(QIAGEN, Hilden, Germany)을 사용하여 인간 GF로부터 RNA를 추출하였다. 분리된 RNA를 DNase Ⅰ로 처리하여 DNA 분해를 확인하였다. RNA 품질은 Agilent Technologies의 TapeStation system(Santa Clara, CA, USA)의 RNA screentape를 사용하여 평가하였으며, 모든 RNA 샘플의 RIN 점수는 7보다 높았다.
다음으로, Illumina TruSeqTM RNA Sample Preparation Kit(Illumina, Inc., San Oiego, CA, USA)를 사용하여 mRNA-Seq 샘플을 얻었다. 즉, 총 RNA 샘플을 RiboZero Human kit 및 RiboZero bacteria kit(Epicentre)로 처리하여 박테리아 및 진핵세포 rRNA를 고갈시킨 후, 열 mRNA 단편화를 수행하였다. RNA 단편은 역전사 효소 및 랜덤 프라이머를 사용하여 첫 번째 가닥 cDNA로 전사되었다. 전사된 cDNA는 DNA Polymerase Ⅰ 및 RNase H를 사용하여 두 번째 가닥 cDNA로 합성되었다. 말단 수리 과정 후에, 하나의 'A' 염기를 단편에 첨가하고, 어댑터를 연결하여 흐름셀(flow cell) 상에 혼성화를 위한 cDNA를 준비하였다. 최종적으로 PCR 산물을 정제하고 농축시켜 cDNA 라이브러리(Macrogen, Seoul, Korea)를 만들었다. cDNA 라이브러리는 HiSeq 2000(Illumina)에서 시퀀싱되어, 약 10 억 쌍의 페어드 앤드 리드(paired-end reads, 2x101 bp)를 얻었다.
5.
전사체
분석
먼저, Trimmomatic(버전 0.33)을 사용하여 4 가지 시료의 RNA-seq 데이터를 사전 처리하여 어댑터 서열, 폴리-N 서열, 또는 낮은 품질의 염기(평균 Phred 점수 15 이하)를 제거한 깨끗한 판독 값(reads)을 얻었다. 손질된 판독 값은 기본 파라미터 하에서 Tophal2에 의해 인간 및 F. nucleatum 게놈으로 정렬되었다. 게놈 서열, 및 인간 돌연변이(GRCh38) 및 F. nucleatum의 주석(annotation)은 NCBI 게놈 데이터베이스 (https://www.ncbi.nlm.nih.gov/genome)에서 얻었다. mRNA 전사체의 정량을 위하여, 최종 손질된 판독 값을 Cufflinks(v2.2.1)에 넣었다. 달리 명시하지 않는 한, 분석에 사용된 모든 유전자 발현 수준은 FPKM(Fagment Per Kilobase of exon per Million fragments mapped) 단위로 표시된다. 차등 발현 분석은 Cufflinks(v2.2.1)를 사용하여 수행하였으며, 시각화는 R(R Development Core Team, R for Statistical Compllting, Vienna, Austria)에 의해 수행되었다.
본 분석의 절차는 도 1에 간결하게 설명되어 있다.
6. 유전자 존재론(Gene ontology, GO), 네트워크 및 경로 분석
각각 GATHER tool(http://gather.genome.duke.edu) 및 Ingenuity Pathway Analysis(IPA) 버전 8.0(Ingenuity® Systems, www.ingenuity.com)을 사용하여 차등 발현 유전자(Differentially Expressed Genes, DEGs)의 GO 및 기능적 경로 분석을 수행하였다.
GF 노화와 관련된 F. nucleatum 대사 경로의 독성 분석을 조사하기 위하여, KEGG 경로 비교 분석을 수행하였다.
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실시예
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1. RNA 시퀀싱 데이터 분석
F. nucleatum 감염 및 노화에 대한 구강섬유아세포(gingival fibroblasts, GF)의 변화를 확인하기 위하여, RNA-seq 기술을 사용하여 게놈 전체 전사체 분석을 수행함으로써 F. nucleatum 감염 또는 비감염 여부에 따른, 젊은 GF(P4) 및 노화된 GF(P22)의 유전자 발현 변화를 확인하였다. 생성된 원(RAW) 시퀀스 데이터를 손질(trimming)한 후, 각 샘플의 깨끗한 판독 값을 먼저 인간 게놈에 매핑하고, F. nucleatum 감염된(F. n-감염) 샘플에서 맵핑되지 않은 판독 값을 F. nucleatum 게놈에서 재매핑하였다.
그 결과, 표 1에 나타낸 바와 같이, 4 개의 샘플(비감염 GF(P4), F. n-감염 GF(P4), 비감염 GF(P22), 및 F. n-감염 GF(P22))로부터 전체 100 Gb의 원(raw) 시퀀스 데이터가 생성되었으며, F. n-감염 GF(P4) 및 GF(P22)에서 각각 총 433,937 건 및 109,468 건의 서열 판독 값이 F. nucleatum 게놈과 일치하였다. GC 함량은 인간 reference 게놈으로 매핑하여 얻어진 서열 판독 값의 백분율(각각 51.11 % 및 51.08 %)과 다른 유사성(각각 35.1 % 및 32.7 %)을 나타냈다. 이러한 결과는, 인간 DNA와 상동성이 없는 세균-특이적 서열이 잘 달성되었음을 의미한다.
Samples | Reference | Total reads (Raw data) |
Total reads (w/o adaptor) |
Aligned pairs | Multiple alignments | Concordant pair alignments |
비감염 GF(P4) | Homo sapiens | 240,914,330 | 240,59 1,122 | 109,770,915 | 4,661,202 | 108,834,930 (90.5%)* |
Fn-감염 GF(P4) | Homo sapiens F. nucleatum ATCC25586 |
249,525,110 | 249,311,972 | 107,274,408 473,131 |
3,153,643 39,194 |
106,723,775 (85.6%) 433,937 (0.1741%) |
비감염 GF(P22) | Homo sapiens | 266,758,386 | 266,438,682 | 124,654,404 | 2,965,534 | 123,496,658 (92.7%) |
Fn-감염 GF(P22) | Homo sapiens F. nucleatum ATCC25586 |
266,580,404 | 259,574,938 | 121,806,945 111 ,166 |
4,613,353 1,698 |
120,318,603 (92.7%) 109,468 (0.0422%) |
* Percentage of concordant pair alignment
또한, 정규화된 FPKM 값의 분포는 도 2에 나타내었으며, 1:1 비교하여 유전자 발현의 분포를 산점도(scatter plots)로 표시하였다. 전반적인 발현 양상은 서로 비슷하게 나타났다(R 값은 0.89에서 0.91까지).
2. 차등 발현 분석
먼저, 구강섬유아세포(GF)의 F. nucleatum 감염에 대한 노화-관련 변화를 확인하기 위하여, 감염 또는 노화 상태의 전사체 프로파일을 비교하였다. 먼저, 젊은(P4) 및 노화된 패시지(P22)에서, 비감염 GF 및 F. n-감염 GF 사이의 유전자 발현 양상을 확인하고, 다음으로 비감염 및 F. n-감염 조건에서, 젊은 GF(P4) 및 노화된 GF(P22) 사이의 유전자 발현 양상을 확인하였다.
그 결과, 도 3A에 나타낸 바와 같이, 먼저, 젊은 GF(P4) 및 노화된 GF(P22)에서 비감염 GF 및 F. n-감염에 따라 각각 차등 발현되는 88 개 및 40 개 유전자를 확인하였다. 이 유전자는 각각 젊은 GF 및 노화된 GF의 F. nucleatum에 대한 숙주 반응을 나타낸다. 또한, 비감염 상태에서는 GF(P4) 및 GF(P22) 사이에서 유의하게 변형된 유전자를 발견하지 못하였으나, F. n-감염 상태에서는 GF(P4) 및 GF(P22) 사이에서 유의하게 차등 발현되는 62 개의 유전자를 발견하였다. 이 유전자는 F. nucleatum 감염에 대한 숙주 반응의 노화 관련 변화를 의미한다.
차등 발현된 유전자의 전체 목록은 표 2 내지 4에 나타내었으며, 상기 결과를 종합하여 도 4에 나타내었다.
Gene Symbol | Uninfected GF(P4) (FPKM) | F. n-infected GF(P4) (FPKM) | Fold change | p-value | q-value | Description |
PTX3 | 77.53 | 2761.75 | 35.62 | 5.0E-05 | 1.2E-02 | pentraxin 3 |
CCL2 | 73.40 | 2676.51 | 36.47 | 5.0E-05 | 1.2E-02 | chemokine (C-C motif) ligand 2 |
IL8 | 0.85 | 1630.11 | 1921.79 | 5.0E-05 | 1.2E-02 | interleukin 8 |
CXCL1 | 1.95 | 1154.64 | 592.86 | 5.0E-05 | 1.2E-02 | chemokine (C-X-C motif) ligand 1 (melanoma growth stimulating activity, alpha) |
PTGS2 | 9.33 | 807.97 | 86.58 | 5.0E-05 | 1.2E-02 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) |
LOC102723726,TNFAIP2 | 18.90 | 794.80 | 42.06 | 5.0E-05 | 1.2E-02 | TNF alpha induced protein 2 |
TNFAIP6 | 14.53 | 684.66 | 47.12 | 5.0E-05 | 1.2E-02 | TNF alpha induced protein 6 |
IL6 | 8.80 | 544.08 | 61.82 | 5.0E-05 | 1.2E-02 | interleukin 6 |
SERPINE1 | 42.15 | 542.06 | 12.86 | 5.0E-05 | 1.2E-02 | serpin peptidase inhibitor, clade E (nexin, plasminogen activator inhibitor type 1), member 1 |
TFPI2 | 17.18 | 329.22 | 19.17 | 5.0E-05 | 1.2E-02 | tissue factor pathway inhibitor 2 |
CXCL2 | 0.96 | 308.47 | 321.45 | 5.0E-05 | 1.2E-02 | chemokine (C-X-C motif) ligand 2 |
ERRFI1 | 33.28 | 246.56 | 7.41 | 1.5E-04 | 3.2E-02 | ERBB receptor feedback inhibitor 1 |
SLC39A14 | 31.63 | 242.81 | 7.68 | 1.0E-04 | 2.3E-02 | solute carrier family 39 (zinc transporter), member 14 |
G0S2 | 5.25 | 229.07 | 43.64 | 5.0E-05 | 1.2E-02 | G0/G1 switch 2 |
ICAM1,ICAM4,ICAM5 | 8.03 | 228.69 | 28.48 | 5.0E-05 | 1.2E-02 | toll-like receptor adaptor molecule |
CXCL6 | 1.72 | 227.09 | 132.26 | 5.0E-05 | 1.2E-02 | chemokine (C-X-C motif) ligand 6 |
TNFAIP3 | 1.48 | 219.88 | 149.07 | 5.0E-05 | 1.2E-02 | TNF alpha induced protein 3 |
SPHK1 | 19.31 | 211.05 | 10.93 | 2.0E-04 | 4.0E-02 | sphingosine kinase 1 |
MSC | 17.45 | 197.21 | 11.30 | 1.0E-04 | 2.3E-02 | musculin |
MMP3 | 3.64 | 182.37 | 50.10 | 5.0E-05 | 1.2E-02 | matrix metallopeptidase 3 |
NFKB1 | 17.76 | 160.54 | 9.04 | 5.0E-05 | 1.2E-02 | nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 |
NFKBIZ,NXPE3 | 20.42 | 150.94 | 7.39 | 1.0E-04 | 2.3E-02 | uclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, zeta|neurexophilin and PC-esterase domain family member 3 |
NINJ1 | 13.12 | 135.72 | 10.34 | 5.0E-05 | 1.2E-02 | ninjurin 1 |
IRF1 | 13.49 | 127.60 | 9.46 | 5.0E-05 | 1.2E-02 | interferon regulatory factor 1 |
LOC102724685,NR4A3,STX17 | 18.70 | 126.23 | 6.75 | 5.0E-05 | 1.2E-02 | nuclear receptor subfamily 4 group A member 3 , syntaxin 17 |
ACKR3 | 9.65 | 114.60 | 11.88 | 5.0E-05 | 1.2E-02 | atypical chemokine receptor 3 |
ZC3H12A | 3.18 | 113.34 | 35.61 | 5.0E-05 | 1.2E-02 | zinc finger CCCH-type containing 12A |
TNFAIP8 | 7.98 | 103.22 | 12.94 | 5.0E-05 | 1.2E-02 | TNF alpha induced protein 8 |
RCAN1 | 11.62 | 100.04 | 8.61 | 5.0E-05 | 1.2E-02 | regulator of calcineurin 1 |
BCL2A1 | 5.26 | 98.89 | 18.81 | 5.0E-05 | 1.2E-02 | BCL2-related protein A1 |
GEM | 5.79 | 79.34 | 13.71 | 5.0E-05 | 1.2E-02 | GTP binding protein overexpressed in skeletal muscle |
IFIT3 | 6.12 | 77.35 | 12.64 | 5.0E-05 | 1.2E-02 | interferon induced protein with tetratricopeptide repeats 3 |
GBP1 | 11.34 | 64.85 | 5.72 | 2.5E-04 | 4.6E-02 | immunoglobulin (CD79A) binding protein 1 |
BMP2 | 5.78 | 64.77 | 11.20 | 5.0E-05 | 1.2E-02 | bone morphogenetic protein 2 |
PTGES | 8.17 | 64.58 | 7.91 | 5.0E-05 | 1.2E-02 | prostaglandin E synthase |
TUBB2A | 6.22 | 63.60 | 10.22 | 5.0E-05 | 1.2E-02 | tubulin, beta 2A class IIa |
NFKB2 | 7.87 | 60.73 | 7.71 | 5.0E-05 | 1.2E-02 | nuclear factor of kappa light polypeptide gene enhancer in B-cells 2 (p49/p100) |
PMAIP1 | 8.88 | 57.09 | 6.43 | 2.5E-04 | 4.6E-02 | phorbol-12-myristate-13-acetate-induced protein 1 |
SMOX | 6.76 | 56.12 | 8.30 | 5.0E-05 | 1.2E-02 | spermine oxidase |
NEDD9 | 3.49 | 55.23 | 15.83 | 5.0E-05 | 1.2E-02 | neural precursor cell expressed, developmentally down-regulated 9 |
CH25H | 1.16 | 54.79 | 47.16 | 5.0E-05 | 1.2E-02 | cholesterol 25-hydroxylase |
RELB | 2.94 | 52.31 | 17.80 | 5.0E-05 | 1.2E-02 | v-rel avian reticuloendotheliosis viral oncogene homolog B |
IL11 | 2.97 | 50.93 | 17.16 | 5.0E-05 | 1.2E-02 | interleukin 11 |
IL32 | 6.01 | 49.00 | 8.15 | 1.0E-04 | 2.3E-02 | interleukin 32 |
CCRN4L | 2.94 | 47.23 | 16.08 | 5.0E-05 | 1.2E-02 | CCR4 carbon catabolite repression 4-like (S. cerevisiae) |
ANGPTL4 | 4.82 | 45.73 | 9.50 | 5.0E-05 | 1.2E-02 | angiopoietin like 4 |
HBEGF | 0.82 | 41.38 | 50.63 | 5.0E-05 | 1.2E-02 | heparin-binding EGF-like growth factor |
GCH1 | 0.72 | 41.22 | 57.31 | 5.0E-05 | 1.2E-02 | GTP cyclohydrolase 1 |
FZD8 | 2.10 | 40.85 | 19.46 | 5.0E-05 | 1.2E-02 | frizzled class receptor 8 |
PDGFA | 4.02 | 40.41 | 10.05 | 5.0E-05 | 1.2E-02 | platelet-derived growth factor alpha polypeptide |
SLC2A1 | 4.99 | 39.11 | 7.84 | 5.0E-05 | 1.2E-02 | solute carrier family 2 (facilitated glucose transporter), member 1 |
HAS2 | 5.29 | 38.33 | 7.25 | 1.0E-04 | 2.3E-02 | hyaluronan synthase 2 |
MAP2K3 | 5.21 | 36.72 | 7.05 | 2.5E-04 | 4.6E-02 | mitogen-activated protein kinase kinase 3 |
SHB | 4.10 | 35.31 | 8.62 | 5.0E-05 | 1.2E-02 | Src homology 2 domain containing adaptor protein B |
VCAM1 | 5.89 | 34.88 | 5.92 | 2.5E-04 | 4.6E-02 | vascular cell adhesion molecule 1 |
RRAD | 1.91 | 34.35 | 17.98 | 5.0E-05 | 1.2E-02 | Ras-related associated with diabetes |
ITPRIP | 5.08 | 33.63 | 6.61 | 2.5E-04 | 4.6E-02 | inositol 1,4,5-trisphosphate receptor interacting protein |
ENC1 | 5.02 | 32.88 | 6.54 | 5.0E-05 | 1.2E-02 | ectodermal-neural cortex 1 (with BTB domain) |
IRAK2 | 3.02 | 31.65 | 10.50 | 5.0E-05 | 1.2E-02 | interleukin 1 receptor associated kinase 2 |
GPR68 | 2.64 | 31.30 | 11.87 | 5.0E-05 | 1.2E-02 | G protein-coupled receptor 68 |
FAM83G | 3.89 | 25.65 | 6.59 | 1.5E-04 | 3.2E-02 | family with sequence similarity 83 member G |
MFSD2A | 0.29 | 25.14 | 86.79 | 2.5E-04 | 4.6E-02 | major facilitator superfamily domain containing 2A |
SERPINB2 | 0.37 | 22.90 | 61.11 | 1.5E-04 | 3.2E-02 | serpin peptidase inhibitor, clade B (ovalbumin), member 2 |
EREG | 0.47 | 22.03 | 46.95 | 5.0E-05 | 1.2E-02 | epiregulin |
IFIT2 | 2.30 | 22.03 | 9.56 | 5.0E-05 | 1.2E-02 | interferon induced protein with tetratricopeptide repeats 2 |
CD274 | 0.54 | 21.99 | 40.98 | 5.0E-05 | 1.2E-02 | CD274 molecule |
BCOR | 2.40 | 21.85 | 9.10 | 5.0E-05 | 1.2E-02 | BCL6 corepressor |
TSLP | 0.72 | 20.60 | 28.59 | 5.0E-05 | 1.2E-02 | thymic stromal lymphopoietin |
BIRC3 | 0.44 | 20.60 | 47.19 | 1.5E-04 | 3.2E-02 | baculoviral IAP repeat containing 3 |
RASD1 | 2.38 | 20.20 | 8.49 | 1.0E-04 | 2.3E-02 | RAS, dexamethasone-induced 1 |
NKX3-1 | 1.60 | 17.78 | 11.12 | 5.0E-05 | 1.2E-02 | NK3 homeobox 1 |
JPH2 | 3.04 | 16.74 | 5.51 | 2.5E-04 | 4.6E-02 | junctophilin 2 |
TRAF1 | 0.81 | 12.26 | 15.08 | 5.0E-05 | 1.2E-02 | TNF receptor associated factor 1 |
EGR3 | 0.89 | 11.82 | 13.29 | 5.0E-05 | 1.2E-02 | early growth response 3 |
NUAK2 | 0.83 | 10.67 | 12.91 | 1.0E-04 | 2.3E-02 | NUAK family, SNF1-like kinase, 2 |
ZNF469 | 1.10 | 10.50 | 9.56 | 5.0E-05 | 1.2E-02 | zinc finger protein 469 |
NFATC1 | 0.85 | 9.33 | 11.02 | 5.0E-05 | 1.2E-02 | nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 1 |
HUNK | 0.51 | 6.05 | 11.87 | 2.5E-04 | 4.6E-02 | hormonally up-regulated Neu-associated kinase |
IL1A | 0.00 | 1.63 | - | 5.0E-05 | 1.2E-02 | interleukin 1 alpha |
IFNB1 | 0.00 | 1.06 | - | 5.0E-05 | 1.2E-02 | interferon, beta 1, fibroblast |
ZFP42 | 0.00 | 0.15 | - | 5.0E-05 | 1.2E-02 | ZFP42 zinc finger protein |
TXNIP | 110.14 | 1.57 | 0.01 | 5.0E-05 | 1.2E-02 | thioredoxin interacting protein |
ADAMTS15 | 17.87 | 1.86 | 0.10 | 5.0E-05 | 1.2E-02 | ADAM metallopeptidase with thrombospondin type 1 motif 15 |
RP4-697P8.3 | 1.10 | 0.00 | - | 5.0E-05 | 1.2E-02 | long noncoding RNA |
LIF | 2.48 | 328.35 | 132.61 | 5.0E-05 | 1.2E-02 | leukemia inhibitory factor |
NFKBIA | 22.59 | 402.56 | 17.82 | 5.0E-05 | 1.2E-02 | nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha |
MAP3K8 | 5.02 | 61.42 | 12.24 | 5.0E-05 | 1.2E-02 | mitogen-activated protein kinase kinase kinase 8 |
NR4A1 | 5.52 | 49.98 | 9.05 | 5.0E-05 | 1.2E-02 | nuclear receptor subfamily 4 group A member 1 |
Gene Symbol | Uninfected GF(P22) (FPKM) |
F. n-infected GF(P22) (FPKM) | Fold change | p-value | q-value | Description |
SEMA6B | 0.00 | 0.24 | 5.0E-05 | 3.0E-02 | sema domain, transmembrane domain (TM), and cytoplasmic domain, (semaphorin) 6B | |
PTPRD | 0.01 | 0.55 | 95.69 | 5.0E-05 | 3.0E-02 | protein tyrosine phosphatase, receptor type, D |
EYA1 | 0.22 | 7.69 | 34.95 | 1.0E-04 | 4.9E-02 | EYA transcriptional coactivator and phosphatase 1 |
SYTL2 | 0.58 | 9.20 | 15.94 | 5.0E-05 | 3.0E-02 | synaptotagmin like 2 |
SFRP2 | 0.56 | 19.47 | 35.03 | 5.0E-05 | 3.0E-02 | secreted frizzled-related protein 2 |
TRIB1 | 1.67 | 25.54 | 15.30 | 1.0E-04 | 4.9E-02 | tribbles pseudokinase 1 |
PTGFRN | 0.58 | 27.23 | 46.98 | 5.0E-05 | 3.0E-02 | prostaglandin F2 receptor inhibitor |
CHODL | 0.13 | 34.46 | 268.50 | 1.0E-04 | 4.9E-02 | chondrolectin |
CPE | 6.72 | 52.27 | 7.77 | 1.0E-04 | 4.9E-02 | carboxypeptidase E |
CSRNP1 | 3.98 | 59.50 | 14.94 | 5.0E-05 | 3.0E-02 | cysteine-serine-rich nuclear protein 1 |
SMAD7 | 6.74 | 67.27 | 9.98 | 1.0E-04 | 4.9E-02 | SMAD family member 7 |
BHLHE40 | 4.73 | 82.85 | 17.53 | 5.0E-05 | 3.0E-02 | basic helix-loop-helix family member e40 |
TM4SF1 | 4.37 | 100.53 | 22.99 | 5.0E-05 | 3.0E-02 | transmembrane 4 L six family member 1 |
NPTX1 | 3.39 | 102.91 | 30.37 | 5.0E-05 | 3.0E-02 | neuronal pentraxin I |
INSIG1 | 7.39 | 120.22 | 16.26 | 5.0E-05 | 3.0E-02 | insulin induced gene 1 |
MAFF | 15.23 | 136.42 | 8.96 | 5.0E-05 | 3.0E-02 | v-maf avian musculoaponeurotic fibrosarcoma oncogene homolog F |
KLF10 | 7.32 | 191.49 | 26.16 | 5.0E-05 | 3.0E-02 | Kruppel-like factor 10 |
GADD45B | 19.73 | 215.07 | 10.90 | 5.0E-05 | 3.0E-02 | growth arrest and DNA damage inducible beta |
DHRS3 | 23.01 | 253.13 | 11.00 | 5.0E-05 | 3.0E-02 | dehydrogenase/reductase (SDR family) member 3 |
ID3 | 72.99 | 544.66 | 7.46 | 5.0E-05 | 3.0E-02 | EP300 interacting inhibitor of differentiation 3 |
FLOT1,IER3 | 73.34 | 723.36 | 9.86 | 5.0E-05 | 3.0E-02 | flotillin 1 , immediate early response 3 |
ID1 | 96.11 | 1162.16 | 12.09 | 1.0E-04 | 4.9E-02 | inhibitor of DNA binding 1, dominant negative helix-loop-helix protein |
SNORD3A | 556.69 | 7878.18 | 14.15 | 5.0E-05 | 3.0E-02 | small nucleolar RNA, C/D box 3A |
SYNPO2 | 44.61 | 5.44 | 0.12 | 5.0E-05 | 3.0E-02 | synaptopodin 2 |
POSTN | 968.11 | 53.97 | 0.06 | 5.0E-05 | 3.0E-02 | periostin, osteoblast specific factor |
RPS16 | 579.07 | 30.73 | 0.05 | 5.0E-05 | 3.0E-02 | ribosomal protein S16 |
CYTL1 | 359.00 | 28.69 | 0.08 | 5.0E-05 | 3.0E-02 | cytokine like 1 |
NOV | 194.08 | 18.44 | 0.10 | 5.0E-05 | 3.0E-02 | nephroblastoma overexpressed |
CST1,CST4 | 157.65 | 3.98 | 0.03 | 5.0E-05 | 3.0E-02 | cystatin SN, cystatin S |
SOD3 | 113.62 | 12.17 | 0.11 | 1.0E-04 | 4.9E-02 | superoxide dismutase 3, extracellular |
FMOD | 72.51 | 7.13 | 0.10 | 5.0E-05 | 3.0E-02 | fibromodulin |
DIO2 | 59.95 | 0.98 | 0.02 | 5.0E-05 | 3.0E-02 | deiodinase, iodothyronine, type II |
HAPLN1 | 43.55 | 2.23 | 0.05 | 5.0E-05 | 3.0E-02 | hyaluronan and proteoglycan link protein 1 |
CMKLR1 | 13.06 | 1.49 | 0.11 | 1.0E-04 | 4.9E-02 | chemerin chemokine-like receptor 1 |
TMEM178B | 8.27 | 0.28 | 0.03 | 5.0E-05 | 3.0E-02 | transmembrane protein 178B |
PLCXD3 | 6.07 | 0.23 | 0.04 | 1.0E-04 | 4.9E-02 | phosphatidylinositol-specific phospholipase C, X domain containing 3 |
LIF | 6.85 | 355.65 | 51.88 | 5.0E-05 | 3.0E-02 | leukemia inhibitory factor |
NFKBIA | 15.76 | 299.90 | 19.03 | 5.0E-05 | 3.0E-02 | nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha |
MAP3K8 | 2.81 | 27.68 | 9.83 | 5.0E-05 | 3.0E-02 | mitogen-activated protein kinase kinase kinase 8 |
NR4A1 | 3.63 | 176.59 | 48.67 | 5.0E-05 | 3.0E-02 | nuclear receptor subfamily 4 group A member 1 |
Gene Symbol | F. n-infected GF(P4) (FPKM) |
F. n-infected GF(P22) (FPKM) |
Fold change | p-value | q-value | Description |
ID1 | 150.82 | 1044.03 | 6.92 | 5.0E-05 | 2.3E-02 | inhibitor of DNA binding 1, dominant negative helix-loop-helix protein |
GADD45B | 14.03 | 196.62 | 14.01 | 5.0E-05 | 2.3E-02 | growth arrest and DNA damage inducible beta |
TIPARP | 29.81 | 187.94 | 6.30 | 5.0E-05 | 2.3E-02 | TCDD-inducible poly(ADP-ribose) polymerase |
KLF10 | 23.13 | 172.26 | 7.45 | 5.0E-05 | 2.3E-02 | Kruppel-like factor 10 |
SGK1 | 21.82 | 126.96 | 5.82 | 1.5E-04 | 4.8E-02 | serum/glucocorticoid regulated kinase 1 |
IL8 | 1649.19 | 118.88 | 0.07 | 5.0E-05 | 2.3E-02 | immediate early response 5-like |
IER5L | 20.17 | 114.75 | 5.69 | 5.0E-05 | 2.3E-02 | immediate early response 5-like |
FAM43A | 11.41 | 104.09 | 9.12 | 5.0E-05 | 2.3E-02 | family with sequence similarity 43 member A |
TM4SF1 | 10.28 | 91.45 | 8.90 | 5.0E-05 | 2.3E-02 | transmembrane 4 L six family member 1 |
PTX3 | 2807.05 | 85.64 | 0.03 | 5.0E-05 | 2.3E-02 | pentraxin 3 |
HES1 | 1.10 | 83.41 | 75.81 | 5.0E-05 | 2.3E-02 | hes family bHLH transcription factor 1 |
SNAI1 | 6.57 | 61.00 | 9.28 | 5.0E-05 | 2.3E-02 | snail family zinc finger 1 |
CSRNP1 | 7.34 | 54.08 | 7.36 | 5.0E-05 | 2.3E-02 | cysteine-serine-rich nuclear protein 1 |
STC2 | 8.20 | 53.56 | 6.53 | 5.0E-05 | 2.3E-02 | stanniocalcin 2 |
CXCL1 | 1165.34 | 52.90 | 0.05 | 5.0E-05 | 2.3E-02 | chemokine (C-X-C motif) ligand 1 (melanoma growth stimulating activity, alpha) |
CXCL2 | 312.76 | 44.78 | 0.14 | 5.0E-05 | 2.3E-02 | chemokine (C-X-C motif) ligand 2 |
LOC102723726,TNFAIP2 | 827.89 | 42.71 | 0.05 | 5.0E-05 | 2.3E-02 | TNF alpha induced protein 2 |
PLEKHF1 | 1.99 | 39.78 | 19.96 | 1.0E-04 | 3.9E-02 | pleckstrin homology and FYVE domain containing 1 |
IL6 | 567.62 | 36.27 | 0.06 | 5.0E-05 | 2.3E-02 | interleukin 6 |
EPGN | 4.01 | 30.82 | 7.68 | 1.5E-04 | 4.8E-02 | epithelial mitogen |
RPS16 | 798.43 | 27.75 | 0.03 | 5.0E-05 | 2.3E-02 | ribosomal protein S16 |
ALDH3A1 | 0.72 | 25.92 | 35.90 | 5.0E-05 | 2.3E-02 | aldehyde dehydrogenase 3 family member A1 |
NFKB1 | 163.17 | 21.69 | 0.13 | 5.0E-05 | 2.3E-02 | nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 |
GDF5 | 0.68 | 21.65 | 31.64 | 1.5E-04 | 4.8E-02 | growth differentiation factor 5 |
SFRP2 | 113.42 | 17.60 | 0.16 | 1.5E-04 | 4.8E-02 | secreted frizzled-related protein 2 |
G0S2 | 233.40 | 16.38 | 0.07 | 5.0E-05 | 2.3E-02 | G0/G1 switch 2 |
CXCL3 | 334.75 | 14.81 | 0.04 | 5.0E-05 | 2.3E-02 | chemokine (C-X-C motif) ligand 3 |
ICAM1,ICAM4,ICAM5 | 232.88 | 13.06 | 0.06 | 5.0E-05 | 2.3E-02 | intercellular adhesion molecule |
SOD3 | 87.29 | 10.87 | 0.12 | 5.0E-05 | 2.3E-02 | superoxide dismutase 3, extracellular |
EDNRB | 81.38 | 9.82 | 0.12 | 5.0E-05 | 2.3E-02 | endothelin receptor type B |
PTGES | 65.80 | 9.17 | 0.14 | 1.0E-04 | 3.9E-02 | prostaglandin E synthase |
CADM1 | 0.64 | 8.67 | 13.49 | 1.0E-04 | 3.9E-02 | cell adhesion molecule 1 |
PMAIP1 | 58.03 | 6.99 | 0.12 | 1.5E-04 | 4.8E-02 | phorbol-12-myristate-13-acetate-induced protein 1 |
SMOX | 57.20 | 6.56 | 0.11 | 1.0E-04 | 3.9E-02 | spermine oxidase |
FMOD | 39.71 | 6.48 | 0.16 | 1.5E-04 | 4.8E-02 | fibromodulin |
CCL20 | 162.09 | 5.74 | 0.04 | 5.0E-05 | 2.3E-02 | chemokine (C-C motif) ligand 20 |
RIPK2 | 50.83 | 5.24 | 0.10 | 1.5E-04 | 4.8E-02 | receptor interacting serine/threonine kinase 2 |
KLF6 | 35.51 | 5.05 | 0.14 | 1.0E-04 | 3.9E-02 | Kruppel-like factor 6 |
HIVEP1 | 25.16 | 4.74 | 0.19 | 1.5E-04 | 4.8E-02 | human immunodeficiency virus type I enhancer binding protein 1 |
TNFAIP6 | 695.14 | 4.64 | 0.01 | 5.0E-05 | 2.3E-02 | TNF alpha induced protein 6 |
MMP3 | 185.18 | 4.15 | 0.02 | 5.0E-05 | 2.3E-02 | matrix metallopeptidase 3 |
IFIT3 | 78.48 | 4.11 | 0.05 | 5.0E-05 | 2.3E-02 | interferon induced protein with tetratricopeptide repeats 3 |
CXCL6 | 230.69 | 3.81 | 0.02 | 5.0E-05 | 2.3E-02 | chemokine (C-X-C motif) ligand 6 |
GPC3 | 22.31 | 3.31 | 0.15 | 1.0E-04 | 3.9E-02 | glypican 3 |
BIRC3 | 20.92 | 3.06 | 0.15 | 5.0E-05 | 2.3E-02 | baculoviral IAP repeat containing 3 |
BCL2A1 | 100.23 | 3.00 | 0.03 | 5.0E-05 | 2.3E-02 | BCL2-related protein A1 |
GCH1 | 41.93 | 2.98 | 0.07 | 1.5E-04 | 4.8E-02 | GTP cyclohydrolase 1 |
BMP2 | 65.79 | 2.73 | 0.04 | 5.0E-05 | 2.3E-02 | bone morphogenetic protein 2 |
CH25H | 55.75 | 2.58 | 0.05 | 1.0E-04 | 3.9E-02 | cholesterol 25-hydroxylase |
CSF2 | 46.59 | 2.13 | 0.05 | 5.0E-05 | 2.3E-02 | colony stimulating factor 2 (granulocyte-macrophage) |
MXRA5 | 18.49 | 1.93 | 0.10 | 5.0E-05 | 2.3E-02 | matrix-remodelling associated 5 |
SLC12A7 | 15.47 | 1.59 | 0.10 | 5.0E-05 | 2.3E-02 | solute carrier family 12 (potassium/chloride transporter), member 7 |
MTRNR2L10 | 0.00 | 1.54 | - | 5.0E-05 | 2.3E-02 | MT-RNR2-like 10 |
C11orf96 | 54.03 | 1.47 | 0.03 | 5.0E-05 | 2.3E-02 | chromosome 11 open reading frame 96 |
TSLP | 20.91 | 1.09 | 0.05 | 1.5E-04 | 4.8E-02 | thymic stromal lymphopoietin |
IGF2,INS,INS-IGF2 | 35.88 | 0.94 | 0.03 | 5.0E-05 | 2.3E-02 | insulin like growth factor 2, |
A2M | 9.75 | 0.81 | 0.08 | 5.0E-05 | 2.3E-02 | INS-IGF2 readthrough |
IFIT2 | 22.36 | 0.73 | 0.03 | 5.0E-05 | 2.3E-02 | interferon induced protein with tetratricopeptide repeats 2 |
GPR133 | 11.15 | 0.66 | 0.06 | 5.0E-05 | 2.3E-02 | adhesion G protein-coupled receptor D1 |
PTPRD | 6.89 | 0.50 | 0.07 | 5.0E-05 | 2.3E-02 | protein tyrosine phosphatase, receptor type, D |
HUNK | 6.15 | 0.34 | 0.06 | 5.0E-05 | 2.3E-02 | hormonally up-regulated Neu-associated kinase |
KC6 | 0.00 | 0.22 | - | 1.5E-04 | 4.8E-02 | Keratoconus gene 6 |
도 4를 참조하면, 젊은 GF(P4)에서는 단지 몇 개의 유전자(3 %, 88 개 중 3 개)만 감염에 의해 하향 조절되었고, 대부분의 차등 발현 유전자(97 %, 88 개 중 85 개)가 감염에 의해 상향 조절되었다(도 4A). 그러나, 노화된 GF(P22)에서는 차등 발현 유전자가 젊은 GF에 비해 상대적으로 더 높은 비율(32.5 %, 40 개 중 13 개)로 하향 조절되었고, 반대로 차등 발현 유전자의 67.5 %(40 개 중 27 개)는 감염에 의해 상향 조절되었다(도 4B). 또한, F. n-감염 상태에서 젊은 GF 및 노화된 GF를 직접 비교한 경우, 노화된 GF에서 차등 발현 유전자의 70 %(62 개 중 43 개)가 하향 조절되는 것을 확인하였다(도 4C).
다음으로, 숙주의 노화 상태에 대해 F. nucleatum가 어떻게 반응 하는지 확인하기 위하여, 인간 게놈으로부터 매핑되지 않은 서열 판독 값을 수집하고, 이를 F. nucleatum 게놈에 매핑한 후, GF의 노화 상태에 따라 고도로 발현된 F. nucleatum의 유전자를 동정하여 젊은 GF 및 노화된 GF에서 유전자 발현을 비교한 결과, 하기 표 5, 6에 나타낸 바와 같이, 높은 발현율(10 배 더 증가)을 보이는 유전자를 각각 젊은 GF에서 391 개, 노화된 GF에서 224 개씩 확인하였다.
GF(P4) | ||
Gene | Locus | Fold change |
FNr08 | NC_003454.1:731536-734463 | 686.954 |
FNr01 | NC_003454.1:444878-493887 | 167.562 |
FNr04 | NC_003454.1:526874-529745 | 158.682 |
FNt02 | NC_003454.1:85321-85397 | 139.414 |
FN0479 | NC_003454.1:1127142-1127592 | 104.761 |
FN0083 | NC_003454.1:721319-721604 | 81.042 |
FN0081 | NC_003454.1:720174-720828 | 74.832 |
FN1636 | NC_003454.1:100649-388096 | 70.750 |
FN0210 | NC_003454.1:837137-837356 | 69.963 |
FNr07 | NC_003454.1:729877-731379 | 63.754 |
rplS | NC_003454.1:1071500-1071851 | 60.578 |
FN1078 | NC_003454.1:1724292-1724838 | 59.937 |
FN1635 | NC_003454.1:100649-388096 | 59.072 |
FN1024 | NC_003454.1:1678261-1678570 | 56.707 |
FN0211 | NC_003454.1:837363-837630 | 56.357 |
FN1835 | NC_003454.1:100649-388096 | 56.097 |
FN2037 | NC_003454.1:546858-547227 | 55.561 |
FN0600 | NC_003454.1:1255608-1256109 | 54.887 |
FN1637,rplP | NC_003454.1:100649-388096 | 54.617 |
FN1826 | NC_003454.1:100649-388096 | 51.823 |
FN1203,FN1204 | NC_003454.1:1862400-1863958 | 51.776 |
FN1916 | NC_003454.1:412495-412906 | 50.650 |
FN1630 | NC_003454.1:100649-388096 | 48.300 |
FN1627 | NC_003454.1:100649-388096 | 47.988 |
FN1239 | NC_003454.1:1896492-1897137 | 47.262 |
FN1309 | NC_003454.1:1964995-1965190 | 47.168 |
FN1750 | NC_003454.1:100649-388096 | 46.998 |
FN1093 | NC_003454.1:1738354-1738783 | 46.660 |
FN1270 | NC_003454.1:1926415-1926766 | 46.369 |
FN0377 | NC_003454.1:1005432-1009256 | 46.336 |
FN1628 | NC_003454.1:100649-388096 | 45.440 |
rplF | NC_003454.1:100649-388096 | 43.530 |
FN1451 | NC_003454.1:2131717-2132800 | 43.421 |
FN2045 | NC_003454.1:550463-550892 | 40.697 |
FN1350 | NC_003454.1:2002448-2002933 | 40.207 |
FN0189,FN0190 | NC_003454.1:813342-815773 | 39.543 |
FN1631 | NC_003454.1:100649-388096 | 39.287 |
FN1833 | NC_003454.1:100649-388096 | 39.143 |
FN2038 | NC_003454.1:547273-547786 | 38.779 |
FN0149 | NC_003454.1:777625-778525 | 37.646 |
FN2123 | NC_003454.1:632297-633321 | 37.552 |
FN1118 | NC_003454.1:1760698-1761028 | 37.055 |
rplE | NC_003454.1:100649-388096 | 36.963 |
FN0311 | NC_003454.1:947264-949962 | 36.732 |
FNt06 | NC_003454.1:85673-85751 | 36.600 |
FN1656 | NC_003454.1:100649-388096 | 36.468 |
FN1657 | NC_003454.1:100649-388096 | 35.978 |
secY | NC_003454.1:100649-388096 | 35.755 |
FN1825 | NC_003454.1:100649-388096 | 35.371 |
FN0755 | NC_003454.1:1414752-1415043 | 34.874 |
FN0085,FN0086 | NC_003454.1:723409-724764 | 34.835 |
FN1879 | NC_003454.1:100649-388096 | 33.771 |
tsf | NC_003454.1:100649-388096 | 33.176 |
FN1641 | NC_003454.1:100649-388096 | 33.157 |
rplA | NC_003454.1:547939-548647 | 33.021 |
FN1437 | NC_003454.1:2104669-2110868 | 32.908 |
FN0338 | NC_003454.1:965238-972157 | 32.824 |
FN1911 | NC_003454.1:403338-405375 | 32.778 |
FN0818 | NC_003454.1:1476811-1477271 | 32.757 |
FN0039 | NC_003454.1:678750-679302 | 32.733 |
FN1364 | NC_003454.1:2010752-2017608 | 32.421 |
FN1828 | NC_003454.1:100649-388096 | 32.174 |
FN0150 | NC_003454.1:778592-778820 | 32.170 |
FN2121 | NC_003454.1:629125-629818 | 31.881 |
FN0330 | NC_003454.1:964722-965124 | 31.598 |
FN0556 | NC_003454.1:1208469-1209090 | 31.561 |
FN1210 | NC_003454.1:1869029-1870856 | 31.554 |
FN0528 | NC_003454.1:1184372-1188753 | 31.053 |
FN1836 | NC_003454.1:100649-388096 | 31.043 |
FN1241 | NC_003454.1:1897870-1898602 | 30.768 |
FN1556 | NC_003454.1:77614-79696 | 30.356 |
FN0536 | NC_003454.1:1190095-1191241 | 30.061 |
rplB | NC_003454.1:100649-388096 | 29.991 |
FN0893 | NC_003454.1:1553963-1554386 | 29.989 |
nadE | NC_003454.1:1861611-1862388 | 29.893 |
FN1432 | NC_003454.1:2100518-2101670 | 29.579 |
FN1913 | NC_003454.1:410143-411670 | 29.459 |
FN1643,rplD | NC_003454.1:100649-388096 | 29.398 |
FN1507 | NC_003454.1:12311-12968 | 29.391 |
FN1809 | NC_003454.1:100649-388096 | 29.107 |
FN1794 | NC_003454.1:100649-388096 | 29.101 |
FN1639 | NC_003454.1:100649-388096 | 29.095 |
FN1640 | NC_003454.1:100649-388096 | 28.951 |
FN1914 | NC_003454.1:411732-412080 | 28.746 |
FN1983 | NC_003454.1:444878-493887 | 28.633 |
FN1625,FN1626 | NC_003454.1:100649-388096 | 28.569 |
FN2040 | NC_003454.1:548707-549133 | 27.966 |
FN0482 | NC_003454.1:1128434-1128680 | 27.960 |
rplM | NC_003454.1:960770-964707 | 27.836 |
FN0585,FN0586 | NC_003454.1:1239927-1241917 | 27.725 |
FN0756,FN0757 | NC_003454.1:1415051-1416291 | 27.648 |
FN0758 | NC_003454.1:1416303-1417365 | 27.457 |
rpsB | NC_003454.1:100649-388096 | 27.396 |
FN0798 | NC_003454.1:1455915-1457943 | 27.262 |
secA | NC_003454.1:100649-388096 | 27.178 |
FN0113 | NC_003454.1:746696-747752 | 27.112 |
FN1258 | NC_003454.1:1913881-1914883 | 27.064 |
FN0367 | NC_003454.1:996472-996991 | 27.023 |
rpsL | NC_003454.1:80239-80608 | 26.941 |
FN1375,FN1376,FN1377,FN1378,FN1379,FN1380 | NC_003454.1:2021587-2028955 | 26.879 |
trmE | NC_003454.1:644644-646012 | 26.839 |
FN0332,FN0333,FN0334,FN0335,FN0336,FN0337 | NC_003454.1:965238-972157 | 26.827 |
FN0358 | NC_003454.1:988375-989764 | 26.732 |
FN1617,FN1618 | NC_003454.1:100649-388096 | 26.312 |
FN0795,FN0796 | NC_003454.1:1452527-1455889 | 26.290 |
FN0188 | NC_003454.1:812415-813312 | 25.974 |
FN2032 | NC_003454.1:537210-537405 | 25.971 |
FN0472 | NC_003454.1:1117751-1118255 | 25.805 |
FN0480 | NC_003454.1:1127593-1127899 | 25.706 |
FN1335 | NC_003454.1:1988816-1989101 | 25.334 |
FN1645 | NC_003454.1:100649-388096 | 25.124 |
FN0411 | NC_003454.1:1048379-1048676 | 25.106 |
FN1622 | NC_003454.1:100649-388096 | 25.034 |
FN2123 | NC_003454.1:632297-633321 | 25.019 |
FN1646 | NC_003454.1:100649-388096 | 24.768 |
FN1369 | NC_003454.1:2018868-2019439 | 24.662 |
FN1509 | NC_003454.1:14188-14266 | 24.591 |
FN0924,FN0925,FN0926 | NC_003454.1:1579202-1597554 | 24.442 |
FN0108 | NC_003454.1:743358-744375 | 24.439 |
FN0412 | NC_003454.1:1048688-1049282 | 24.361 |
FN0776 | NC_003454.1:1432083-1433067 | 24.019 |
FN1287 | NC_003454.1:1944504-1944753 | 23.872 |
FN1282 | NC_003454.1:1941358-1941709 | 23.790 |
asnC | NC_003454.1:679313-680897 | 23.669 |
FN1557 | NC_003454.1:79741-80212 | 23.484 |
FN0283,FN0284 | NC_003454.1:912778-914013 | 23.260 |
FN0785 | NC_003454.1:1441285-1442461 | 22.956 |
FNt35 | NC_003454.1:530229-530306 | 22.816 |
FN0101,FN0102,FN0103 | NC_003454.1:736169-739667 | 22.780 |
FN0466 | NC_003454.1:1111440-1112922 | 22.742 |
FN1283,rpsD | NC_003454.1:1941736-1943333 | 22.680 |
FN1517 | NC_003454.1:20965-23545 | 22.673 |
FNt36 | NC_003454.1:549944-550020 | 22.671 |
FN1238 | NC_003454.1:1895283-1896381 | 22.658 |
FN0557 | NC_003454.1:1209689-1210424 | 22.371 |
FN0820 | NC_003454.1:1479499-1480879 | 22.165 |
tuf | NC_003454.1:76341-77526 | 21.599 |
FN1129 | NC_003454.1:1774343-1777925 | 21.598 |
FN0302 | NC_003454.1:936873-937638 | 21.547 |
FN0634 | NC_003454.1:1292379-1294197 | 21.421 |
FN0364 | NC_003454.1:993846-994503 | 21.397 |
FN0116 | NC_003454.1:748392-750216 | 21.311 |
FN1091 | NC_003454.1:1736054-1737398 | 21.280 |
FN0200 | NC_003454.1:826262-826667 | 21.170 |
FN0501 | NC_003454.1:1149676-1152028 | 20.993 |
FN0100 | NC_003454.1:735208-735856 | 20.936 |
FN0488 | NC_003454.1:1133196-1134516 | 20.928 |
rpmA | NC_003454.1:1761028-1761313 | 20.886 |
FN1359,FN1360,FN1361,FN1362,FN1363 | NC_003454.1:2010752-2017608 | 20.866 |
FN1242 | NC_003454.1:1898616-1899699 | 20.798 |
FN1240 | NC_003454.1:1897146-1897869 | 20.520 |
FN1762 | NC_003454.1:100649-388096 | 20.471 |
FN1812 | NC_003454.1:100649-388096 | 20.387 |
FN1117 | NC_003454.1:1760381-1760696 | 20.056 |
FN0311 | NC_003454.1:947264-949962 | 19.963 |
nrdR | NC_003454.1:2171923-2172373 | 19.941 |
FN1332 | NC_003454.1:1986155-1987253 | 19.910 |
thrS | NC_003454.1:1268498-1270361 | 19.853 |
FN1988,FN1989,tnaA | NC_003454.1:444878-493887 | 19.794 |
FN0718,FN0719,FN0720 | NC_003454.1:1375755-1377679 | 19.689 |
FN2098 | NC_003454.1:607462-608236 | 19.653 |
FN1423 | NC_003454.1:2088942-2090160 | 19.557 |
FN2044 | NC_003454.1:550046-550199 | 19.534 |
FN1808 | NC_003454.1:100649-388096 | 19.487 |
FN1859 | NC_003454.1:100649-388096 | 19.460 |
FN1924 | NC_003454.1:421805-423083 | 19.446 |
FNt22 | NC_003454.1:100649-388096 | 19.418 |
FN1285 | NC_003454.1:1943372-1943762 | 19.334 |
FN1231 | NC_003454.1:1887532-1888996 | 19.324 |
FN0360 | NC_003454.1:990943-992446 | 19.283 |
FN1265 | NC_003454.1:1921470-1922079 | 19.199 |
FN0376 | NC_003454.1:1005432-1009256 | 19.193 |
FN0675 | NC_003454.1:1330560-1332180 | 19.160 |
FN1435,FN1436,FN1438,FN1439,FN1440,FN1441 | NC_003454.1:2104669-2110868 | 19.138 |
FN2126 | NC_003454.1:636395-638315 | 19.095 |
FN1393 | NC_003454.1:2049599-2050934 | 19.085 |
FN1092 | NC_003454.1:1737406-1738321 | 19.056 |
FN0777 | NC_003454.1:1433107-1434922 | 19.004 |
FN1533 | NC_003454.1:45439-46411 | 19.001 |
FN1454 | NC_003454.1:2134885-2135749 | 18.989 |
FN0295 | NC_003454.1:928125-929055 | 18.959 |
FN0130 | NC_003454.1:758725-759532 | 18.943 |
FN1977,FN1978 | NC_003454.1:444878-493887 | 18.943 |
FN0865 | NC_003454.1:1523129-1523855 | 18.867 |
FN0005 | NC_003454.1:643895-644639 | 18.795 |
FN0579 | NC_003454.1:1229942-1234778 | 18.736 |
gmk | NC_003454.1:537436-537994 | 18.717 |
FN0147,FN0148 | NC_003454.1:775601-777586 | 18.647 |
FN1481 | NC_003454.1:2162768-2163890 | 18.560 |
FN1623 | NC_003454.1:100649-388096 | 18.527 |
FN1866 | NC_003454.1:100649-388096 | 18.435 |
FN1941 | NC_003454.1:441418-444013 | 18.417 |
glyQ | NC_003454.1:707948-708821 | 18.392 |
rpsM | NC_003454.1:1943807-1944164 | 18.337 |
FN1329 | NC_003454.1:1983431-1983980 | 18.330 |
FN0736 | NC_003454.1:1394747-1395503 | 18.245 |
FN1813 | NC_003454.1:100649-388096 | 18.234 |
FN1811 | NC_003454.1:100649-388096 | 18.189 |
FN0363 | NC_003454.1:993523-993793 | 18.160 |
FN0359 | NC_003454.1:990084-990933 | 18.150 |
FN0822 | NC_003454.1:1481967-1482486 | 18.070 |
FN1985 | NC_003454.1:444878-493887 | 17.989 |
FN0562,FN0563 | NC_003454.1:1214986-1216427 | 17.842 |
FN1505 | NC_003454.1:10535-11009 | 17.816 |
FN0285 | NC_003454.1:914021-914261 | 17.751 |
FNt29 | NC_003454.1:444878-493887 | 17.693 |
FN1428,FN1429,FN1430 | NC_003454.1:2096949-2099292 | 17.657 |
FN0292 | NC_003454.1:925100-926703 | 17.644 |
FN0151 | NC_003454.1:778910-780152 | 17.570 |
FN0725 | NC_003454.1:1384270-1384989 | 17.522 |
FN1424 | NC_003454.1:2090184-2092095 | 17.419 |
FN1519 | NC_003454.1:23552-24882 | 17.343 |
FN1205 | NC_003454.1:1863968-1865252 | 17.267 |
FN0792 | NC_003454.1:1448402-1450424 | 17.224 |
FN0092 | NC_003454.1:728047-729166 | 17.160 |
FN0276 | NC_003454.1:901835-903413 | 16.869 |
FN2125 | NC_003454.1:633814-636250 | 16.812 |
FN0615 | NC_003454.1:1273326-1275051 | 16.726 |
FN1354 | NC_003454.1:2005485-2008055 | 16.702 |
FN0783 | NC_003454.1:1439305-1440451 | 16.626 |
FN1483 | NC_003454.1:2166100-2166613 | 16.619 |
FN0326,FN0327,FN0328,rplT | NC_003454.1:960770-964707 | 16.492 |
FN0658 | NC_003454.1:1314979-1315765 | 16.453 |
FN0201 | NC_003454.1:826681-827809 | 16.434 |
FN1824 | NC_003454.1:100649-388096 | 16.404 |
engB | NC_003454.1:514157-514742 | 16.354 |
FN0462 | NC_003454.1:1107323-1109255 | 16.326 |
FN0088,FN0089 | NC_003454.1:725026-726444 | 16.324 |
FN1165,FN1166,mglC | NC_003454.1:1823037-1827649 | 16.262 |
FN1340 | NC_003454.1:1993442-1994993 | 16.252 |
ychF | NC_003454.1:2010752-2017608 | 16.249 |
FN1972,FN1973,FN1974 | NC_003454.1:444878-493887 | 16.237 |
FN0823 | NC_003454.1:1482506-1484309 | 16.197 |
FN0494 | NC_003454.1:1138916-1139648 | 16.125 |
FN0058 | NC_003454.1:694046-695240 | 16.060 |
FN0203 | NC_003454.1:828887-829691 | 16.010 |
FN0784 | NC_003454.1:1440471-1441260 | 15.938 |
FN1765 | NC_003454.1:100649-388096 | 15.899 |
FN1592,FN1593,FN1594,FN1595 | NC_003454.1:100649-388096 | 15.865 |
FN1661 | NC_003454.1:100649-388096 | 15.814 |
FN1717 | NC_003454.1:100649-388096 | 15.813 |
FN1708 | NC_003454.1:100649-388096 | 15.807 |
FN0309 | NC_003454.1:944238-945921 | 15.795 |
glpQ | NC_003454.1:400685-401759 | 15.753 |
FN1800 | NC_003454.1:100649-388096 | 15.693 |
FN1520 | NC_003454.1:24891-26163 | 15.576 |
FN0306,FN0307 | NC_003454.1:941239-943029 | 15.499 |
FN0454 | NC_003454.1:1099606-1101082 | 15.414 |
FN1605 | NC_003454.1:100649-388096 | 15.391 |
FN1077 | NC_003454.1:1723843-1724095 | 15.371 |
FN0724 | NC_003454.1:1383753-1384257 | 15.339 |
FN0263,FN0264,FN0265,FN0266,FN0267,FN0268,FN0269,FN0270 | NC_003454.1:887665-897800 | 15.280 |
guaA | NC_003454.1:2111724-2113263 | 15.243 |
FN1781 | NC_003454.1:100649-388096 | 15.235 |
asnC | NC_003454.1:679313-680897 | 15.075 |
FN1563 | NC_003454.1:84866-85130 | 15.043 |
FN2088,FN2089,FN2090,FN2091,FN2092,FN2093 | NC_003454.1:599937-603641 | 15.029 |
FN0079 | NC_003454.1:717801-719169 | 14.982 |
FN1984 | NC_003454.1:444878-493887 | 14.918 |
FN0009,FN0010,FN0011 | NC_003454.1:649047-651680 | 14.912 |
FN0054 | NC_003454.1:690975-692196 | 14.904 |
FN0262 | NC_003454.1:887665-897800 | 14.873 |
smpB | NC_003454.1:1264400-1264847 | 14.866 |
FN1069 | NC_003454.1:1714871-1717142 | 14.862 |
FN1315 | NC_003454.1:1969010-1969544 | 14.753 |
FN0204 | NC_003454.1:829711-831466 | 14.718 |
FN0022 | NC_003454.1:660929-661211 | 14.676 |
FN1352 | NC_003454.1:2003595-2004270 | 14.525 |
FN0602 | NC_003454.1:1256788-1257499 | 14.471 |
FN0299 | NC_003454.1:932532-934311 | 14.464 |
FN1138 | NC_003454.1:1785608-1786040 | 14.461 |
FNt07 | NC_003454.1:85759-85836 | 14.451 |
FN2035 | NC_003454.1:538911-542871 | 14.364 |
FN0594 | NC_003454.1:1248924-1249350 | 14.348 |
FN1383 | NC_003454.1:2034544-2037946 | 14.330 |
FN0601 | NC_003454.1:1256191-1256617 | 14.329 |
FN0522,FN0524 | NC_003454.1:1173054-1179733 | 14.234 |
FN2008,FN2009,FN2010 | NC_003454.1:507686-510392 | 14.189 |
FN1975 | NC_003454.1:444878-493887 | 14.142 |
FN0927,FN0928,FN0929,FN0930,FN0931 | NC_003454.1:1579202-1597554 | 14.089 |
FN0361,FN0362 | NC_003454.1:992470-993483 | 14.081 |
FN1349 | NC_003454.1:2000559-2002445 | 14.075 |
FN1211,FN1212 | NC_003454.1:1870872-1873258 | 14.054 |
FN1025 | NC_003454.1:1678713-1680021 | 14.047 |
FN0202 | NC_003454.1:827919-828885 | 14.034 |
FN1763 | NC_003454.1:100649-388096 | 14.030 |
FN2036 | NC_003454.1:542906-546461 | 13.977 |
FN1994 | NC_003454.1:497716-498151 | 13.930 |
FN1827 | NC_003454.1:100649-388096 | 13.918 |
FN1172 | NC_003454.1:1833701-1834804 | 13.916 |
FN1304 | NC_003454.1:1960388-1960853 | 13.849 |
FN1298 | NC_003454.1:1955080-1955716 | 13.839 |
FN1033 | NC_003454.1:1686453-1687635 | 13.832 |
FN0109,FN0110 | NC_003454.1:744422-746148 | 13.762 |
FN1121 | NC_003454.1:1763209-1764730 | 13.732 |
FN1321 | NC_003454.1:1976070-1977480 | 13.589 |
FN0186 | NC_003454.1:810992-811646 | 13.550 |
FN0368,FN0369 | NC_003454.1:997127-998985 | 13.533 |
FN2103 | NC_003454.1:613342-614269 | 13.529 |
FN0065 | NC_003454.1:700072-702244 | 13.360 |
FN1301 | NC_003454.1:1957808-1959428 | 13.305 |
FN1229,FN1230 | NC_003454.1:1886349-1887517 | 13.289 |
FN1900 | NC_003454.1:388383-389376 | 13.243 |
FN1350 | NC_003454.1:2002448-2002933 | 13.231 |
FN1252 | NC_003454.1:1909507-1910194 | 13.196 |
FN0008 | NC_003454.1:648149-649046 | 13.115 |
FN0321 | NC_003454.1:957773-959597 | 13.105 |
FN1596 | NC_003454.1:100649-388096 | 13.079 |
FN1171 | NC_003454.1:1832454-1833651 | 13.066 |
FN1353 | NC_003454.1:2004273-2005476 | 13.002 |
FN0749 | NC_003454.1:1407801-1409019 | 12.970 |
FN1131,FN1132 | NC_003454.1:1778962-1780314 | 12.950 |
FNt38 | NC_003454.1:755222-755307 | 12.914 |
FN1782 | NC_003454.1:100649-388096 | 12.913 |
FN1831 | NC_003454.1:100649-388096 | 12.904 |
FN1896 | NC_003454.1:100649-388096 | 12.822 |
FN0965,FN0966,FN0967 | NC_003454.1:1618417-1621140 | 12.810 |
FN0322 | NC_003454.1:959613-960640 | 12.754 |
FN0002 | NC_003454.1:642687-643023 | 12.736 |
FN0162 | NC_003454.1:790063-791404 | 12.727 |
FN1214,FN1215 | NC_003454.1:1874255-1876257 | 12.678 |
FN2100 | NC_003454.1:609125-610376 | 12.678 |
FN0310 | NC_003454.1:945935-947006 | 12.655 |
FN1021,FN1022 | NC_003454.1:1674727-1677561 | 12.645 |
FN0846 | NC_003454.1:1504381-1505296 | 12.630 |
FN0297 | NC_003454.1:930037-931261 | 12.596 |
FN2068 | NC_003454.1:577534-579076 | 12.588 |
FN0843 | NC_003454.1:1502911-1503476 | 12.560 |
FN0668 | NC_003454.1:1324108-1325047 | 12.507 |
FN1810 | NC_003454.1:100649-388096 | 12.502 |
FN2019 | NC_003454.1:522019-522382 | 12.488 |
FN2082 | NC_003454.1:593346-594981 | 12.412 |
FN0047 | NC_003454.1:684566-685328 | 12.306 |
hppA | NC_003454.1:534118-536134 | 12.267 |
FN0977 | NC_003454.1:1629179-1630670 | 12.212 |
FN1199 | NC_003454.1:1859200-1860253 | 12.186 |
FN1873 | NC_003454.1:100649-388096 | 12.177 |
FN0800 | NC_003454.1:1460036-1460729 | 12.170 |
FN1224,FN1225,FN1226 | NC_003454.1:1882629-1885593 | 12.124 |
FN1130 | NC_003454.1:1777979-1778957 | 12.104 |
FN0207 | NC_003454.1:833757-835086 | 12.095 |
FN1967,FN1968,FN1969,FN1970,FN1971 | NC_003454.1:444878-493887 | 12.069 |
FN0741 | NC_003454.1:1399080-1400046 | 12.063 |
FN2003,FN2004,FN2005 | NC_003454.1:503871-506036 | 12.040 |
FN0976 | NC_003454.1:1628235-1629153 | 12.031 |
FN0041 | NC_003454.1:679313-680897 | 12.006 |
FN0731 | NC_003454.1:1387859-1388393 | 11.994 |
FN0592,lpxC | NC_003454.1:1245851-1248903 | 11.849 |
FN0315 | NC_003454.1:952073-952919 | 11.825 |
FN1506 | NC_003454.1:11010-12120 | 11.728 |
FN1991 | NC_003454.1:494762-496103 | 11.728 |
FN0388 | NC_003454.1:1026689-1027520 | 11.728 |
engA | NC_003454.1:795350-796673 | 11.675 |
FN0174 | NC_003454.1:799566-800523 | 11.592 |
FN1834 | NC_003454.1:100649-388096 | 11.558 |
FN1487 | NC_003454.1:2169648-2170110 | 11.541 |
FN1422 | NC_003454.1:2083444-2088575 | 11.484 |
FN1030,FN1031 | NC_003454.1:1683719-1685890 | 11.437 |
FN0316 | NC_003454.1:953323-953779 | 11.414 |
FN1243 | NC_003454.1:1899713-1900574 | 11.325 |
FN0322 | NC_003454.1:959613-960640 | 11.286 |
upp | NC_003454.1:1128716-1129361 | 11.236 |
FN1392 | NC_003454.1:2049285-2049549 | 11.194 |
FN1192 | NC_003454.1:1854818-1855091 | 11.162 |
FN0558,FN0559,FN0560 | NC_003454.1:1210821-1214279 | 11.066 |
FN0525 | NC_003454.1:1179734-1181930 | 10.999 |
FN0999 | NC_003454.1:1653893-1654937 | 10.945 |
FN1764 | NC_003454.1:100649-388096 | 10.847 |
FN2079 | NC_003454.1:590431-591208 | 10.726 |
FN0491 | NC_003454.1:1136328-1137408 | 10.723 |
FN1619 | NC_003454.1:100649-388096 | 10.702 |
FNt24 | NC_003454.1:100649-388096 | 10.693 |
FN0375 | NC_003454.1:1005432-1009256 | 10.606 |
FN1906 | NC_003454.1:398506-399943 | 10.546 |
FN2016 | NC_003454.1:517073-518938 | 10.498 |
FN1089,FN1090 | NC_003454.1:1733181-1735810 | 10.477 |
FN1421 | NC_003454.1:2083444-2088575 | 10.435 |
FN0475 | NC_003454.1:1122259-1123567 | 10.424 |
FN1458,FN1459 | NC_003454.1:2139066-2141450 | 10.355 |
FN0278 | NC_003454.1:904395-905754 | 10.330 |
FN0576 | NC_003454.1:1226252-1227362 | 10.323 |
FN0970 | NC_003454.1:1622696-1623356 | 10.293 |
FN0932,FN0933,FN0934 | NC_003454.1:1579202-1597554 | 10.263 |
FN0128,FN0129 | NC_003454.1:756790-758430 | 10.196 |
FN1157,FN1158,glpX | NC_003454.1:1814042-1815911 | 10.176 |
FN0887 | NC_003454.1:1547998-1549801 | 10.134 |
FN0084 | NC_003454.1:721711-723154 | 10.107 |
FN0635 | NC_003454.1:1294219-1295083 | 10.045 |
FN0294 | NC_003454.1:927288-928101 | 10.034 |
FN0610 | NC_003454.1:1264954-1268422 | 10.028 |
clpX | NC_003454.1:517073-518938 | 10.009 |
GF(P22) | ||
Gene | Locus | Fold change |
FNt16 | NC_003454.1:100649-388096 | 296186 |
FNt45 | NC_003454.1:1081919-1081996 | 48323.8 |
FN1821 | NC_003454.1:100649-388096 | 34738.7 |
FNt14 | NC_003454.1:100649-388096 | 31262.2 |
FN0702 | NC_003454.1:1361014-1361092 | 24168 |
FN1633 | NC_003454.1:100649-388096 | 23486.3 |
FN1681 | NC_003454.1:100649-388096 | 21776.6 |
FN1674 | NC_003454.1:100649-388096 | 18301.5 |
FNt01 | NC_003454.1:85235-85313 | 17568.9 |
FN1634 | NC_003454.1:100649-388096 | 8243.31 |
FN0231 | NC_003454.1:857327-857441 | 4208.29 |
FN1952 | NC_003454.1:444878-493887 | 3769.54 |
FNt13 | NC_003454.1:100649-388096 | 2618.24 |
FN0797 | NC_003454.1:1452527-1455889 | 620.822 |
FN1043 | NC_003454.1:1694378-1694510 | 498.719 |
FN0919 | NC_003454.1:1574388-1574625 | 484.425 |
FN1073 | NC_003454.1:1720542-1721049 | 359.392 |
FN0051 | NC_003454.1:688872-689351 | 289.453 |
FN0402 | NC_003454.1:1040447-1040624 | 230.353 |
FN0575 | NC_003454.1:1225470-1225644 | 224.712 |
FN0232 | NC_003454.1:857910-858108 | 133.681 |
FN1084 | NC_003454.1:1728800-1729058 | 126.776 |
FN0655 | NC_003454.1:1313511-1313850 | 102.579 |
FN1957 | NC_003454.1:444878-493887 | 99.7833 |
FN2114 | NC_003454.1:624099-624297 | 98.4558 |
FN1852 | NC_003454.1:100649-388096 | 98.33 |
FN1871 | NC_003454.1:100649-388096 | 97.3719 |
FN0199 | NC_003454.1:825922-826225 | 94.4385 |
FN1673 | NC_003454.1:100649-388096 | 92.9704 |
FN1278,FN1279 | NC_003454.1:1936871-1938360 | 86.9742 |
FN1188 | NC_003454.1:1850919-1851417 | 82.8759 |
FN1302 | NC_003454.1:1959508-1959727 | 82.8372 |
FN1545 | NC_003454.1:59272-59557 | 80.6652 |
FN1583,FN1584 | NC_003454.1:95128-96248 | 80.6124 |
FN1328 | NC_003454.1:1983006-1983219 | 80.4023 |
FN0286 | NC_003454.1:914272-914515 | 77.2394 |
FN0429 | NC_003454.1:1071088-1071412 | 75.4542 |
FN0676 | NC_003454.1:1332197-1332470 | 75.2102 |
FN2129 | NC_003454.1:639689-639905 | 74.1361 |
FN0588 | NC_003454.1:1242258-1242492 | 73.7762 |
FN1942 | NC_003454.1:444089-444779 | 71.7464 |
FN1890 | NC_003454.1:100649-388096 | 70.1143 |
FN0256 | NC_003454.1:882347-882527 | 67.0627 |
FN1756 | NC_003454.1:100649-388096 | 66.7586 |
FN1575 | NC_003454.1:86282-86585 | 66.3147 |
FN0686 | NC_003454.1:1342273-1342588 | 62.4737 |
FN1842 | NC_003454.1:100649-388096 | 62.1048 |
FN1861 | NC_003454.1:100649-388096 | 60.4914 |
FN0167 | NC_003454.1:794245-794476 | 59.8087 |
FN1938 | NC_003454.1:438038-438506 | 55.9081 |
FN1391 | NC_003454.1:2048923-2049193 | 55.4497 |
FN0612 | NC_003454.1:1270391-1270892 | 54.5937 |
FN0956 | NC_003454.1:1612547-1612796 | 53.9226 |
FN1081 | NC_003454.1:1727414-1727624 | 53.7403 |
FN0773 | NC_003454.1:1429413-1429695 | 52.777 |
FN0980 | NC_003454.1:1632617-1632875 | 52.6114 |
FN0139 | NC_003454.1:771529-771700 | 50.9116 |
FN0663 | NC_003454.1:1319425-1319857 | 49.7735 |
FN1296 | NC_003454.1:1953721-1954231 | 48.473 |
FN0844 | NC_003454.1:1503669-1503834 | 48.0724 |
FN1881 | NC_003454.1:100649-388096 | 46.8453 |
FN1922 | NC_003454.1:417722-419525 | 46.308 |
FN0845 | NC_003454.1:1504074-1504284 | 46.3011 |
FN1193 | NC_003454.1:1855191-1855461 | 45.8835 |
FN1796 | NC_003454.1:100649-388096 | 45.6853 |
FN0584 | NC_003454.1:1239583-1239877 | 44.5482 |
FN1257 | NC_003454.1:1913310-1913754 | 44.4788 |
FN1740 | NC_003454.1:100649-388096 | 43.8926 |
FN1885 | NC_003454.1:100649-388096 | 42.1667 |
FN2076 | NC_003454.1:587625-587856 | 41.863 |
FN0160 | NC_003454.1:788418-788658 | 41.7649 |
FN0737 | NC_003454.1:1395504-1395834 | 40.8342 |
FN1665 | NC_003454.1:100649-388096 | 40.6129 |
FN1719 | NC_003454.1:100649-388096 | 40.0705 |
FN0974 | NC_003454.1:1626805-1627234 | 40.0415 |
FN1664 | NC_003454.1:100649-388096 | 39.42 |
FN0861 | NC_003454.1:1521827-1522049 | 39.1808 |
FN0365 | NC_003454.1:994631-994949 | 38.9416 |
FN1816 | NC_003454.1:100649-388096 | 38.9178 |
FN0134 | NC_003454.1:769878-770190 | 38.7516 |
FN1795 | NC_003454.1:100649-388096 | 38.6157 |
FN0551 | NC_003454.1:1203415-1204805 | 38.2796 |
FN2124 | NC_003454.1:633340-633802 | 38.0785 |
FN1248 | NC_003454.1:1904689-1905304 | 37.6959 |
FN0401 | NC_003454.1:1039994-1040240 | 37.2245 |
FN0698 | NC_003454.1:1356750-1357167 | 37.1302 |
FN2113 | NC_003454.1:623827-624022 | 37.057 |
FN1010 | NC_003454.1:1664401-1664698 | 36.7644 |
FN1744 | NC_003454.1:100649-388096 | 36.6508 |
FN1602 | NC_003454.1:100649-388096 | 36.5205 |
FN0859 | NC_003454.1:1520809-1521319 | 36.4966 |
FN1006 | NC_003454.1:1661087-1661486 | 35.7727 |
FN1601 | NC_003454.1:100649-388096 | 35.4601 |
FN0104 | NC_003454.1:739707-739986 | 35.4003 |
FN1048 | NC_003454.1:1698050-1699154 | 35.2476 |
FN0852 | NC_003454.1:1510363-1510963 | 35.2267 |
FN1264 | NC_003454.1:1920803-1921268 | 34.2273 |
FN1822 | NC_003454.1:100649-388096 | 34.2236 |
FN1872 | NC_003454.1:100649-388096 | 34.0814 |
FN1598 | NC_003454.1:100649-388096 | 33.101 |
FN1683 | NC_003454.1:100649-388096 | 32.9918 |
FN1720 | NC_003454.1:100649-388096 | 32.4769 |
FN1966 | NC_003454.1:444878-493887 | 32.4611 |
FN0895 | NC_003454.1:1554998-1555463 | 32.202 |
FN1615 | NC_003454.1:100649-388096 | 32.1823 |
FN0394 | NC_003454.1:1032466-1033207 | 32.1653 |
FN1475 | NC_003454.1:2157924-2158797 | 32.0673 |
FN0955 | NC_003454.1:1612017-1612545 | 31.9155 |
FN1869 | NC_003454.1:100649-388096 | 31.4823 |
FN1785 | NC_003454.1:100649-388096 | 31.3492 |
FN0514 | NC_003454.1:1163570-1163972 | 31.3418 |
FN2046 | NC_003454.1:551000-551450 | 31.2184 |
FN0589 | NC_003454.1:1242569-1242893 | 31.0438 |
FN0105 | NC_003454.1:740346-740961 | 30.8145 |
FN1254 | NC_003454.1:1910588-1911104 | 30.7056 |
FN0622 | NC_003454.1:1281417-1282071 | 30.4443 |
FN1387 | NC_003454.1:2042979-2043693 | 30.4287 |
FN0296 | NC_003454.1:929111-929879 | 30.3646 |
FN1659 | NC_003454.1:100649-388096 | 30.3245 |
FN1394 | NC_003454.1:2050944-2051256 | 29.9854 |
FN1552 | NC_003454.1:66290-67235 | 29.9157 |
FN1953 | NC_003454.1:444878-493887 | 29.8956 |
FN1415 | NC_003454.1:2075697-2076855 | 29.859 |
FN0106 | NC_003454.1:741099-741522 | 29.8392 |
FN0640 | NC_003454.1:1297528-1298410 | 29.7941 |
FN1647 | NC_003454.1:100649-388096 | 29.7342 |
FN0135 | NC_003454.1:770377-770665 | 29.3071 |
FN1680 | NC_003454.1:100649-388096 | 29.2733 |
FN1832 | NC_003454.1:100649-388096 | 28.998 |
FN1518 | NC_003454.1:23552-24882 | 28.9337 |
FN0862 | NC_003454.1:1522215-1522461 | 28.7948 |
FN0370 | NC_003454.1:999061-999922 | 28.7619 |
FN1345 | NC_003454.1:1998219-1999047 | 28.689 |
FN1666 | NC_003454.1:100649-388096 | 28.5904 |
FN1479 | NC_003454.1:2160792-2161359 | 28.5354 |
FN0633 | NC_003454.1:1291067-1292312 | 28.4752 |
FN0406 | NC_003454.1:1043599-1044664 | 28.2075 |
FN0626 | NC_003454.1:1285624-1286182 | 28.1057 |
FN1347 | NC_003454.1:1999733-2000390 | 27.9758 |
FN2112 | NC_003454.1:623258-623753 | 27.9138 |
FN1134 | NC_003454.1:1781634-1782102 | 27.9037 |
FN1829 | NC_003454.1:100649-388096 | 27.7808 |
FN1007 | NC_003454.1:1661657-1662542 | 27.676 |
FN1874 | NC_003454.1:100649-388096 | 27.6067 |
FN2064 | NC_003454.1:575302-575806 | 27.6029 |
FN1752 | NC_003454.1:100649-388096 | 27.5611 |
FN0885 | NC_003454.1:1544844-1545705 | 27.2795 |
FN0099 | NC_003454.1:734821-735175 | 27.1855 |
FN0907 | NC_003454.1:1565413-1566085 | 27.1701 |
FN0180 | NC_003454.1:804935-805412 | 26.9446 |
FN1056 | NC_003454.1:1703832-1704432 | 26.8213 |
FN0339 | NC_003454.1:972174-972648 | 26.6597 |
FN0534 | NC_003454.1:1188889-1189426 | 26.4741 |
FN0628 | NC_003454.1:1287288-1288347 | 26.3039 |
FN1198 | NC_003454.1:1857768-1859031 | 26.2149 |
FN1223 | NC_003454.1:1882073-1882601 | 26.1522 |
FN1476 | NC_003454.1:2158811-2159486 | 26.0342 |
FN1755 | NC_003454.1:100649-388096 | 25.6512 |
FN1105 | NC_003454.1:1750180-1750678 | 25.5813 |
FN1539 | NC_003454.1:52600-53152 | 25.3244 |
FN1722 | NC_003454.1:100649-388096 | 25.23 |
FN0185 | NC_003454.1:809356-810559 | 25.2166 |
FN1308 | NC_003454.1:1964279-1964921 | 25.2069 |
FN0120 | NC_003454.1:752807-752981 | 24.7938 |
FN1803 | NC_003454.1:100649-388096 | 24.7619 |
FN0191 | NC_003454.1:815891-817325 | 24.7254 |
FN0034 | NC_003454.1:675528-676179 | 24.6431 |
FN0035 | NC_003454.1:676329-676992 | 24.5307 |
FN0765 | NC_003454.1:1420931-1422020 | 24.3741 |
FN0209 | NC_003454.1:836266-836860 | 24.073 |
FN0726 | NC_003454.1:1385055-1385355 | 23.8308 |
FN0916 | NC_003454.1:1572154-1572604 | 23.7657 |
FN0923 | NC_003454.1:1577627-1579067 | 23.6697 |
FN0619 | NC_003454.1:1278899-1279745 | 23.6635 |
FN0492,FN0493 | NC_003454.1:1137543-1138642 | 23.6357567 |
FN0632 | NC_003454.1:1290431-1290866 | 23.52 |
FN1333 | NC_003454.1:1987253-1987670 | 23.5148 |
FN1901 | NC_003454.1:389453-390107 | 23.1461 |
FN1195 | NC_003454.1:1855693-1856329 | 23.1197 |
FN1368 | NC_003454.1:2018246-2018861 | 23.1139 |
FN1780 | NC_003454.1:100649-388096 | 22.7197 |
FN0788 | NC_003454.1:1444029-1444449 | 22.4386 |
FN0922 | NC_003454.1:1576677-1577616 | 22.3602 |
FN0678 | NC_003454.1:1334108-1334711 | 22.014 |
FN1686 | NC_003454.1:100649-388096 | 21.6872 |
FN1116 | NC_003454.1:1759660-1760272 | 21.5224 |
FN0661 | NC_003454.1:1317868-1318273 | 21.4653 |
FN1607 | NC_003454.1:100649-388096 | 21.3926 |
FN0710 | NC_003454.1:1369014-1369692 | 21.0041 |
FN0896 | NC_003454.1:1555486-1555870 | 20.6374 |
FN1815 | NC_003454.1:100649-388096 | 20.5528 |
FN0166 | NC_003454.1:793871-794237 | 20.5513 |
FN0331 | NC_003454.1:965238-972157 | 20.2373 |
FN0026 | NC_003454.1:664424-664981 | 19.8545 |
FN1409 | NC_003454.1:2069148-2070693 | 19.5984 |
FN1599 | NC_003454.1:100649-388096 | 19.4607 |
FN0631 | NC_003454.1:1289957-1290419 | 19.053 |
FN1741,FN1742 | NC_003454.1:100649-388096 | 18.82696998 |
FN1878 | NC_003454.1:100649-388096 | 18.6041 |
FN1710 | NC_003454.1:100649-388096 | 18.3411 |
FN0059 | NC_003454.1:695292-695679 | 18.07414877 |
FN1895 | NC_003454.1:100649-388096 | 18.0624 |
FN0473 | NC_003454.1:1118431-1119001 | 17.9177 |
FN1739 | NC_003454.1:100649-388096 | 17.0717 |
FN0045,FN0046 | NC_003454.1:683151-684325 | 16.86803782 |
FN1724 | NC_003454.1:100649-388096 | 16.8544 |
FN0487 | NC_003454.1:1131845-1132862 | 16.68169729 |
FN1721 | NC_003454.1:100649-388096 | 16.6754 |
FN1405 | NC_003454.1:2064426-2064996 | 16.5408 |
FN0449,FN0450 | NC_003454.1:1092822-1094990 | 16.5277013 |
FN0960 | NC_003454.1:1615214-1615709 | 15.6912 |
FN1541,FN1542 | NC_003454.1:55354-57252 | 15.2105731 |
FN0836 | NC_003454.1:1498941-1499238 | 15.1694 |
FN0464 | NC_003454.1:1109814-1110147 | 14.4466 |
FN0030 | NC_003454.1:667259-667736 | 14.1281 |
FN2111 | NC_003454.1:622523-623183 | 13.9857 |
FN1342,FN1343 | NC_003454.1:1996180-1997322 | 13.62975234 |
FN0407 | NC_003454.1:1044743-1045268 | 13.41148985 |
FN0229 | NC_003454.1:856414-857307 | 13.3563 |
FN1434 | NC_003454.1:2102627-2104601 | 12.77477088 |
FN0260 | NC_003454.1:886350-886728 | 12.70189693 |
cvrA | NC_003454.1:80966-82550 | 12.06494258 |
FN1374 | NC_003454.1:2021587-2028955 | 11.05772237 |
FN2065,FN2066 | NC_003454.1:575989-576833 | 10.82563193 |
또한, KEGG 데이터베이스를 사용하여 이들 유전자의 세균 경로를 분석한 결과, 노화된 GF(224 개 중 11 개)에 비하여 젊은 GF에서 상대적으로 많은 수의 F. nucleatum 유전자(391 개 중 65 개)가 신진 대사 경로에 매핑되었고, 젊은 GF에서 더 다양한 종류의 세균 경로가 검출되었다. 예를 들어, 젊은 GF에서는 해당 과정, 지방산 대사, 부틸레이트 대사 및 LPS/펩티도글리칸 생합성 경로가 밝혀졌지만, 노화된 GF에서는 이러한 경로가 전혀 나타나지 않았다.
3. GO 농축 분석
차등 발현 유전자(DEGs)의 생물학적 관련성을 조사하기 위하여 GATHER 데이터베이스를 사용하여 GO 분석을 수행하고, 각 차등 발현 유전자 세트의 상위 5 가지 주요 GO 주석(annotations)을 하기 표 7에 나타내었다.
Comparison groups | GO annotation | p-value* | Genes |
DEGs of uninfected GF(P4) vs. F. n-infected GF(P4) |
GO:0006955 [4]: immune response | <0.0001 | CCL2, CXCL1, CXCL2, CXCL6, GBP1, GEM, GPR68, IFIT2, IFIT3, IFNB1, 1L11, IL1A, IL32, IL6, IL8, IRAK2, IRF1, LIF, NFKB1, PDCD1LG1, PTGES, PTGS2, PTX3, TNF AIP6 |
GO:0006952 [5]: defense response | <0.0001 | CCL2, CXCL1, CXCL2, CXCL6, GBP1, GEM, GPR68, IFIT2, IFIT3, IFNB1, 1L11, IL1A, IL32, IL6, IL8, IRAK2, IRF1, LIF, NFKB1, PDCD1LG1, PTGES, PTGS2, PTX3, TNF AIP6 | |
GO:0009607 [4]: response to biotic stimulus | <0.0001 | CCL2, CXCL1, CXCL2, CXCL6, GBP1, GEM, GPR68, IFIT2, IFIT3, IFNB1, 1L11, IL1A, IL32, IL6, IL8, IRAK2, IRF1, LIF, NFKB1, NFKBIA, PDCD1LG1, PTGES, PTGS2, PTX3, TNF AIP6 | |
GO:0051243 [5]: negative regulation of cellular physiological processes | <0.0001 | ANGPTL4, BCL2A1, BIRC3, CCL2, CXCL1, IFNB1, IL1A, IL6, IL8, NFKB1, NFKBIA, SERPINB2, TNFAIP3, TNFAIP8 | |
GO:0006954 [5]: inflammatory response | <0.0001 | CCL2, CXCL1, CXCL2, CXCL6, GPR68, IL1A, IL8, IRAK2, NFKB1, PTGS2, PTX3, TNFAIP6 | |
DEGs of uninfected GF(P22) vs. F. n-infected GF(P22) |
GO:0007179 [8]: transforming growth factor beta receptor signaling pathway | <0.0001 | FMOD, KLFIO, SMAD7 |
GO:0007178 [7] : transmembrane receptor protein serine/threonine kinase signaling pathway | 0.0001 | FMOD, KLFIO, SMAD7 | |
GO:0007167 [6]: enzyme-linked receptor protein signaling pathway | 0.0004 | FMOD, KLFIO, PTPRD, SMAD7 | |
GO:0007275 [2]: development | 0.0008 | CMKLR1, EYA1, GADD45B, ID1, ID3, IER3, KLFIO, LIF, NOV, NPTX1, POSTN, SEMA6B | |
G0:000 1501 [5]: skeletal development | 0.04 | CMKLR1, KLF10, POSTN | |
DEGs of F. n-infected GF(P4) vs. F. n-infected GF(P22) |
GO:0006954 [5]: inflammatory response | <0.0001 | CCL20, CXCL1, CXCL2, CXCL3, CXCL6, IL8, NFKB1, PTX3, RIPK2, TNFAIP6 |
GO:0009611 [5]: response to wounding | <0.0001 | CCL20, CSF2, CXCL1, CXCL2, CXCL3, CXCL6, IL8, NFKB1, PTX3, RIPK2, TNFAIP6 | |
GO:0006955 [4]: immune response | <0.0001 | CCL20, CSF2, CXCL1, CXCL2, CXCL3, CXCL6, IFIT2, IFIT3, IL6, IL8, KLF6, NFKB1, PTGES, PTX3, RIPK2, TNFAIP6 | |
GO:0009613 [5]: response to pest, pathogen, or parasite | <0.0001 | CCL20, CSF2, CXCL1, CXCL2, CXCL3, CXCL6, IL6, IL8, NFKB1, PTGES, PTX3, RIPK2, TNFAIP6 | |
GO:0043207 [5]: response to external biotic stimulus | <0.0001 | CCL20, CSF2, CXCL1, CXCL2, CXCL3, CXCL6, IL6, IL8, NFKB1, PTGES, PTX3, RIPK2, TNFAIP6 |
*p-value is calculated using Fischer's exact test, which calculates the ratio of the pathway-associated genes in the experimental data to the total number of genes in that pathway.
상기 표 7에 나타낸 바와 같이, 감염에 대한 차등 발현 유전자의 생물학적 과정은 젊은 GF(P4) 및 노화된 GF(P22)에서 현저하게 다르게 나타났다. 예를 들어, 젊은 GF의 차등 발현 유전자 88 개는 면역 반응, 생체 자극에 대한 반응 및 염증 반응과 같은 세균 감염에 대한 숙주 방어에 더 많이 관여하는 것으로 나타난 반면, 노화된 GF의 차등 발현 유전자 44 개는 형질전환 생장 인자(transforming growth factor) 베타 수용체 신호 전달 경로 및 골격 발달과 같은 세포 유지에 매우 관여하는 것으로 나타났다. 또한, F. nucleatum-감염 젊은 GF 및 노화된 GF 사이의 공통적인 차등 발현 유전자 62 개는 염증 반응, 상처에 대한 반응 및 면역 반응과 같은 세균 감염에 대한 숙주 반응에 관여하는 것으로 나타났다.
4. 젊은 또는 노화된
GF
-특이적 차등 발현 유전자(
DEGs
) 분석
상기 실시예 3의 결과에 기초하여, 동정된 차등 발현 유전자의 F. nucleatum-감염에 대한 특이적 반응을 확인하였다.
먼저, 젊은 GF의 88 개 유전자와 노화된 GF의 40 개 유전자를 F. nucleatum-감염 젊은 GF 및 노화된 GF의 공통적인 62 개 유전자와 비교하였다. 그 결과, 도 5A 및 5B에 나타낸 바와 같이, 중첩 영역에서 각각 24 개 및 10 개의 유전자를 확인하였다. 이 유전자는 F. nucleatum 감염에 대하여 GF 노화의 정도에 따라 다르게 나타나는 유전자(각각 젊은 GF-특이적 유전자 및 노화된 GF-특이적 유전자 해당)를 의미한다.
또한, 젊은 GF의 88 개 유전자를 노화된 GF의 40 개 유전자와 직접 비교하였다. 그 결과, 도 5C에 나타낸 바와 같이, 중첩 영역에서 4 개의 유전자를 확인하였다. 이 유전자는 F. nucleatum 감염에 대한 GF-특이적 유전자를 의미한다.
상기 각 유전자는 표 8 내지 10에 나타내었다.
- F. nucleatum-감염 젊은 GF 및 노화된 GF의 공통적인 유전자와 젊은 GF(P4)에서 차등 발현되는 유전자의 중첩 분석
- F. nucleatum-감염 젊은 GF 및 노화된 GF의 공통적인 유전자와 노화된 GF(P22)에서 차등 발현되는 유전자의 중첩 분석
- GF(P4) 및 GF(P22)에서 차등 발현되는 유전자의 중첩 분석
또한, 이들 유전자의 발현 수준을 나타내는 Heatmap을 도 6에 나타내었다.
도 6에 나타낸 바와 같이, 24 및 10 유전자의 발현 수준은 F. nucleatum 감염 후, 젊은 GF 및 노화된 GF에서 각각 현저히 변화되었으며, 또한, 젊은 GF 및 노화된 GF 사이에서 유의미하게 차별적으로 발현되었다(도 6A 및 B). 또한, 4 개의 유전자는 젊은 GF 및 노화된 GF 모두에서 F. nucleatum 감염에 반응하는 동일한 발현 패턴을 나타내는 것을 확인하였다(도 6C). 이들 유전자는 F. nucleatum 감염에 대한 노화-독립적인 방식의 숙주 반응을 의미한다.
5. 차등 발현 유전자(
DEGs
)의 기능성 주석 분석
상기 실시예 4의 결과에 기초하여, 각 유전자 세트의 생물학적 관련성을 조사하기 위하여, 지식 데이터베이스 IPA를 사용하여 차등 발현 유전자에 기능적 주석을 달았다. 표 2, 3, 4, 7 및 8에 제시된 각 차등 발현 유전자 세트의 상위 10 개 세부 카테고리를 표 11에 나타내었다.
Comparison groups | Categories | Diseases or Functions Annotation | p-value | # Molecules | Molecules | |
A | DEG of uninfected GF(P4) vs. F. n-infected GF(P4) |
Cell Death and Survival | apoptosis | 4.E-26 | 61 | ANGPTL4,BCL2A1,BIRC3,BMP2,CCL2,CD274,CXCL1,CXCL2,CXCL8,EGR3,ENC1,EREG,ERRFI1,G0S2,GEM,HAS2,HBEGF,HUNK,ICAM1,IFIT2,IFIT3,IFNB1,IL11,IL1A,IL32,IL6,IRAK2,IRF1,LIF,MAP2K3,MAP3K8,MMP3,NEDD9,NFATC1,NFKB1,NFKB2,NFKBIA,NFKBIZ,NINJ1,NR4A1,NR4A3,NUAK2,PMAIP1,PTGES,PTGS2,RASD1,RCAN1,RELB,RRAD,SERPINE1,SLC2A1,SMOX,SPHK1,TFPI2,TNFAIP2,TNFAIP3,TNFAIP8,TRAF1,TSLP,TXNIP,ZC3H12A |
Cell Death and Survival | cell death | 1.E-25 | 67 | ACKR3,ANGPTL4,BCL2A1,BIRC3,BMP2,CCL2,CD274,CXCL1,CXCL2,CXCL8,EGR3,ENC1,EREG,ERRFI1,G0S2,GCH1,GEM,HAS2,HBEGF,HUNK,ICAM1,IFIT2,IFIT3,IFNB1,IL11,IL1A,IL32,IL6,IRAK2,IRF1,ITPRIP,LIF,MAP2K3,MAP3K8,MMP3,NEDD9,NFATC1,NFKB1,NFKB2,NFKBIA,NFKBIZ,NINJ1,NKX3-1,NR4A1,NR4A3,NUAK2,PMAIP1,PTGES,PTGS2,RASD1,RCAN1,RELB,RRAD,SERPINB2,SERPINE1,SLC2A1,SMOX,SPHK1,TFPI2,TNFAIP2,TNFAIP3,TNFAIP8,TRAF1,TSLP,TXNIP,VCAM1,ZC3H12A | ||
Cellular Growth and Proliferation | proliferation of cells | 1.E-24 | 68 | ACKR3,ADAMTS15,ANGPTL4,BCL2A1,BIRC3,BMP2,CCL2,CD274,CXCL1,CXCL2,CXCL8,EGR3,ENC1,EREG,ERRFI1,FZD8,G0S2,GBP1,GCH1,GEM,HAS2,HBEGF,HUNK,ICAM1,IFIT3,IFNB1,IL11,IL1A,IL32,IL6,IRF1,LIF,MAP2K3,MAP3K8,MMP3,NEDD9,NFATC1,NFKB1,NFKB2,NFKBIA,NINJ1,NKX3-1,NR4A1,NR4A3,PDGFA,PMAIP1,PTGES,PTGS2,PTX3,RASD1,RCAN1,RELB,RRAD,SERPINB2,SERPINE1,SHB,SLC2A1,SMOX,SPHK1,TFPI2,TNFAIP3,TNFAIP6,TNFAIP8,TRAF1,TSLP,TUBB2A,TXNIP,VCAM1 | ||
Hematological System Development and Function, Tissue Morphology | quantity of leukocytes | 4.E-24 | 38 | ACKR3,BCL2A1,BIRC3,CCL2,CD274,CXCL2,CXCL6,CXCL8,EGR3,GPR68,HBEGF,ICAM1,IFNB1,IL11,IL1A,IL6,IRF1,LIF,MAP3K8,MMP3,NEDD9,NFATC1,NFKB1,NFKB2,NFKBIA,NR4A1,PTGS2,RELB,SERPINB2,SERPINE1,SLC2A1,SPHK1,TNFAIP3,TRAF1,TSLP,TXNIP,VCAM1,ZC3H12A | ||
Hematological System Development and Function, Tissue Morphology | quantity of blood cells | 3.E-23 | 39 | ACKR3,BCL2A1,BIRC3,CCL2,CD274,CXCL2,CXCL6,CXCL8,EGR3,GPR68,HBEGF,ICAM1,IFNB1,IL11,IL1A,IL6,IRF1,LIF,MAP3K8,MMP3,NEDD9,NFATC1,NFKB1,NFKB2,NFKBIA,NR4A1,PTGS2,RCAN1,RELB,SERPINB2,SERPINE1,SLC2A1,SPHK1,TNFAIP3,TRAF1,TSLP,TXNIP,VCAM1,ZC3H12A | ||
Cell Death and Survival | necrosis | 7.E-23 | 58 | ACKR3,BCL2A1,BIRC3,BMP2,CCL2,CD274,CXCL1,CXCL2,CXCL8,EGR3,ENC1,EREG,G0S2,GCH1,GEM,HAS2,HBEGF,ICAM1,IFNB1,IL11,IL1A,IL32,IL6,IRAK2,IRF1,ITPRIP,LIF,MAP2K3,MAP3K8,MMP3,NEDD9,NFATC1,NFKB1,NFKB2,NFKBIA,NFKBIZ,NR4A1,NR4A3,PMAIP1,PTGES,PTGS2,RASD1,RCAN1,RELB,RRAD,SERPINB2,SERPINE1,SLC2A1,SMOX,SPHK1,TFPI2,TNFAIP3,TNFAIP8,TRAF1,TSLP,TXNIP,VCAM1,ZC3H12A | ||
Cellular Movement | cell movement | 9.E-23 | 53 | ACKR3,ANGPTL4,BMP2,CCL2,CD274,CXCL1,CXCL2,CXCL6,CXCL8,EREG,ERRFI1,GBP1,GEM,HAS2,HBEGF,ICAM1,IFIT2,IFNB1,IL11,IL1A,IL32,IL6,LIF,MAP2K3,MAP3K8,MMP3,NEDD9,NFATC1,NFKB1,NFKB2,NFKBIA,NFKBIZ,NINJ1,NKX3-1,NR4A1,NUAK2,PDGFA,PTGES,PTGS2,PTX3,RCAN1,RELB,SERPINB2,SERPINE1,SLC2A1,SPHK1,TFPI2,TNFAIP3,TNFAIP6,TNFAIP8,TSLP,VCAM1,ZC3H12A | ||
Tissue Morphology | quantity of cells | 2.E-22 | 48 | ACKR3,BCL2A1,BIRC3,BMP2,CCL2,CD274,CXCL1,CXCL2,CXCL6,CXCL8,EGR3,ERRFI1,GPR68,HBEGF,ICAM1,IFNB1,IL11,IL1A,IL6,IRF1,LIF,MAP3K8,MMP3,NEDD9,NFATC1,NFKB1,NFKB2,NFKBIA,NKX3-1,NR4A1,NR4A3,PDGFA,PMAIP1,PTGES,PTGS2,RCAN1,RELB,SERPINB2,SERPINE1,SLC2A1,SPHK1,TNFAIP3,TRAF1,TSLP,TXNIP,VCAM1,ZC3H12A,ZFP42 | ||
Cellular Movement | cellular infiltration | 4.E-22 | 28 | CCL2,CD274,CXCL2,CXCL8,GBP1,ICAM1,IL1A,IL32,IL6,LIF,MAP3K8,NFATC1,NFKB1,NFKB2,NFKBIA,NFKBIZ,NINJ1,NR4A1,PDGFA,PTGES,PTGS2,PTX3,SERPINE1,TNFAIP3,TNFAIP8,TSLP,VCAM1,ZC3H12A | ||
Cellular Movement | migration of cells | 2.E-21 | 49 | ACKR3,ANGPTL4,BMP2,CCL2,CD274,CXCL1,CXCL2,CXCL6,CXCL8,EREG,ERRFI1,HAS2,HBEGF,ICAM1,IFIT2,IFNB1,IL11,IL1A,IL32,IL6,LIF,MAP2K3,MAP3K8,MMP3,NEDD9,NFATC1,NFKB1,NFKB2,NFKBIA,NFKBIZ,NINJ1,NKX3-1,NR4A1,PDGFA,PTGES,PTGS2,PTX3,RCAN1,SERPINB2,SERPINE1,SLC2A1,SPHK1,TFPI2,TNFAIP3,TNFAIP6,TNFAIP8,TSLP,VCAM1,ZC3H12A | ||
B | DEG of uninfected GF(P22) vs. F. n-infected GF(P22) |
Skeletal and Muscular System Development and Function | morphology of skeleton | 6.E-10 | 10 | DHRS3,EYA1,FMOD,HAPLN1,ID1,KLF10,LIF,NOV,POSTN,SFRP2 |
Cellular Development, Connective Tissue Development and Function, Tissue Development | differentiation of connective tissue cells | 2.E-09 | 13 | CMKLR1,CYTL1,GADD45B,ID1,ID3,INSIG1,KLF10,LIF,NOV,NR4A1,POSTN,SFRP2,SMAD7 | ||
Connective Tissue Disorders, Organismal Injury and Abnormalities, Skeletal and Muscular Disorders, Skeletal and Muscular System Development and Function | abnormal morphology of skeleton | 4.E-09 | 9 | DHRS3,EYA1,FMOD,HAPLN1,ID1,KLF10,LIF,NOV,SFRP2 | ||
Embryonic Development, Organismal Development | development of body axis | 7.E-09 | 15 | CSRNP1,CYTL1,DHRS3,DIO2,EYA1,FMOD,ID1,ID3,INSIG1,LIF,NFKBIA,POSTN,SFRP2,SMAD7,TM4SF1 | ||
Embryonic Development, Organismal Development | development of head | 3.E-08 | 14 | CSRNP1,CYTL1,DHRS3,DIO2,EYA1,FMOD,ID1,ID3,INSIG1,LIF,NFKBIA,POSTN,SMAD7,TM4SF1 | ||
Organismal Development | abnormal morphology of body cavity | 3.E-08 | 15 | BHLHE40,CMKLR1,DHRS3,EYA1,FMOD,ID1,ID3,LIF,MAP3K8,NFKBIA,NOV,POSTN,SMAD7,SYTL2,TRIB1 | ||
Organismal Development | morphology of body cavity | 5.E-08 | 16 | BHLHE40,CMKLR1,DHRS3,EYA1,FMOD,ID1,ID3,LIF,MAP3K8,NFKBIA,NOV,NR4A1,POSTN,SMAD7,SYTL2,TRIB1 | ||
Connective Tissue Development and Function, Skeletal and Muscular System Development and Function, Tissue Development | size of bone | 1.E-07 | 8 | EYA1,HAPLN1,ID1,KLF10,LIF,NOV,POSTN,SFRP2 | ||
Cell Morphology, Tissue Morphology | morphology of connective tissue cells | 1.E-07 | 8 | ID1,INSIG1,KLF10,LIF,NOV,NR4A1,POSTN,TRIB1 | ||
Cancer, Organismal Injury and Abnormalities, Reproductive System Disease | mammary tumor | 2.E-07 | 17 | BHLHE40,CPE,EYA1,GADD45B,ID1,KLF10,LIF,MAP3K8,NFKBIA,NPTX1,NR4A1,POSTN,PTPRD,SEMA6B,SFRP2,TM4SF1,TRIB1 | ||
C | DEG of F. n-infected GF(P4) vs F. n-infected GF(P22) |
Cell Death and Survival | apoptosis | 2.E-16 | 40 | A2M,ALDH3A1,BCL2A1,BIRC3,BMP2,CADM1,CSF2,CSRNP1,CXCL1,CXCL2,CXCL8,EDNRB,FMOD,G0S2,GADD45B,GDF5,GPC3,HES1,HUNK,ICAM1,ID1,IFIT2,IFIT3,IGF2,IL6,KLF10,KLF6,MMP3,NFKB1,PLEKHF1,PMAIP1,PTGES,RIPK2,SFRP2,SGK1,SMOX,SNAI1,SOD3,TNFAIP2,TSLP |
Cell Death and Survival | cell death | 6.E-16 | 44 | A2M,ALDH3A1,BCL2A1,BIRC3,BMP2,CADM1,CSF2,CSRNP1,CXCL1,CXCL2,CXCL3,CXCL8,EDNRB,FMOD,G0S2,GADD45B,GCH1,GDF5,GPC3,HES1,HUNK,ICAM1,ID1,IFIT2,IFIT3,IGF2,IL6,KLF10,KLF6,MMP3,NFKB1,PLEKHF1,PMAIP1,PTGES,RIPK2,RPS16,SFRP2,SGK1,SLC12A7,SMOX,SNAI1,SOD3,TNFAIP2,TSLP | ||
Cell Death and Survival | necrosis | 2.E-14 | 38 | A2M,ALDH3A1,BCL2A1,BIRC3,BMP2,CADM1,CSF2,CXCL1,CXCL2,CXCL3,CXCL8,EDNRB,FMOD,G0S2,GADD45B,GCH1,GDF5,GPC3,HES1,ICAM1,ID1,IGF2,IL6,KLF10,KLF6,MMP3,NFKB1,PLEKHF1,PMAIP1,PTGES,RIPK2,RPS16,SFRP2,SGK1,SMOX,SNAI1,SOD3,TSLP | ||
Connective Tissue Disorders, Inflammatory Disease, Organismal Injury and Abnormalities, Skeletal and Muscular Disorders | Rheumatic Disease | 7.E-14 | 26 | BMP2,CCL20,CSF2,CXCL1,CXCL2,CXCL3,CXCL6,CXCL8,EDNRB,FMOD,G0S2,GADD45B,GDF5,HES1,ICAM1,IL6,MMP3,NFKB1,PTGES,PTX3,RIPK2,RPS16,SGK1,SOD3,TNFAIP6,TSLP | ||
Cellular Growth and Proliferation, Tissue Development | proliferation of epithelial cells | 2.E-13 | 18 | BCL2A1,CSF2,CXCL3,CXCL8,EDNRB,EPGN,GDF5,GPC3,HES1,HUNK,ID1,IGF2,IL6,KLF10,NFKB1,SFRP2,TNFAIP6,TSLP | ||
Connective Tissue Disorders, Inflammatory Disease, Inflammatory Response, Organismal Injury and Abnormalities, Skeletal and Muscular Disorders | inflammation of joint | 3.E-13 | 24 | BMP2,CCL20,CSF2,CXCL1,CXCL2,CXCL3,CXCL6,CXCL8,FMOD,G0S2,GADD45B,GDF5,HES1,ICAM1,IL6,MMP3,NFKB1,PTGES,PTX3,RIPK2,RPS16,SOD3,TNFAIP6,TSLP | ||
Cellular Growth and Proliferation | proliferation of cells | 7.E-13 | 42 | A2M,ALDH3A1,BCL2A1,BIRC3,BMP2,CADM1,CCL20,CSF2,CXCL1,CXCL2,CXCL3,CXCL8,EDNRB,EPGN,FMOD,G0S2,GADD45B,GCH1,GDF5,GPC3,HES1,HUNK,ICAM1,ID1,IFIT3,IGF2,IL6,KLF10,KLF6,MMP3,NFKB1,PMAIP1,PTGES,PTX3,RIPK2,SFRP2,SGK1,SMOX,SNAI1,STC2,TNFAIP6,TSLP | ||
Tissue Development | growth of epithelial tissue | 8.E-13 | 20 | BCL2A1,BMP2,CSF2,CXCL1,CXCL3,CXCL8,EDNRB,EPGN,GDF5,GPC3,HES1,HUNK,ID1,IGF2,IL6,KLF10,NFKB1,SFRP2,TNFAIP6,TSLP | ||
Cellular Movement | migration of cells | 9.E-13 | 31 | A2M,BMP2,CCL20,CSF2,CXCL1,CXCL2,CXCL3,CXCL6,CXCL8,EDNRB,FMOD,GDF5,GPC3,ICAM1,ID1,IFIT2,IGF2,IL6,KLF6,MMP3,NFKB1,PTGES,PTX3,RIPK2,SFRP2,SGK1,SNAI1,SOD3,TM4SF1,TNFAIP6,TSLP | ||
Cancer, Organismal Injury and Abnormalities | metastasis | 3.E-12 | 21 | BMP2,CSF2,CXCL1,CXCL2,CXCL3,CXCL6,CXCL8,EDNRB,GCH1,ICAM1,ID1,IGF2,IL6,KLF6,MMP3,NFKB1,PTX3,SLC12A7,SNAI1,SOD3,TM4SF1 | ||
D | Overlapping A and C | Gastrointestinal Disease, Inflammatory Disease, Organismal Injury and Abnormalities | esophagitis | 1.E-12 | 7 | BCL2A1,CXCL1,CXCL2,CXCL6,CXCL8,TNFAIP6,TSLP |
Connective Tissue Disorders, Inflammatory Disease, Inflammatory Response, Organismal Injury and Abnormalities, Skeletal and Muscular Disorders | osteoarthritis | 1.E-11 | 9 | BMP2,CXCL2,CXCL6,ICAM1,IL6,MMP3,NFKB1,PTGES,PTX3 | ||
Inflammatory Response | inflammatory response | 3.E-11 | 13 | BCL2A1,BIRC3,CXCL1,CXCL2,CXCL6,CXCL8,ICAM1,IL6,NFKB1,PTGES,PTX3,TNFAIP6,TSLP | ||
Connective Tissue Disorders, Inflammatory Disease, Inflammatory Response, Organismal Injury and Abnormalities, Skeletal and Muscular Disorders | inflammation of joint | 4.E-11 | 14 | BMP2,CXCL1,CXCL2,CXCL6,CXCL8,G0S2,ICAM1,IL6,MMP3,NFKB1,PTGES,PTX3,TNFAIP6,TSLP | ||
Gastrointestinal Disease, Hematological Disease, Immunological Disease, Inflammatory Disease, Organismal Injury and Abnormalities | eosinophilia of esophagus | 8.E-11 | 6 | BCL2A1,CXCL1,CXCL2,CXCL6,TNFAIP6,TSLP | ||
Cellular Movement, Hematological System Development and Function, Immune Cell Trafficking, Inflammatory Response | influx of phagocytes | 1.E-10 | 6 | CXCL1,CXCL2,CXCL6,IL6,PTX3,TSLP | ||
Cell Death and Survival | apoptosis | 2.E-10 | 19 | BCL2A1,BIRC3,BMP2,CXCL1,CXCL2,CXCL8,G0S2,HUNK,ICAM1,IFIT2,IFIT3,IL6,MMP3,NFKB1,PMAIP1,PTGES,SMOX,TNFAIP2,TSLP | ||
Cellular Movement | influx of myeloid cells | 2.E-10 | 6 | CXCL1,CXCL2,CXCL6,IL6,PTX3,TSLP | ||
Digestive System Development and Function, Gastrointestinal Disease, Hepatic System Development and Function, Hepatic System Disease, Inflammatory Disease, Inflammatory Response, Organ Development, Organismal Injury and Abnormalities, Psychological Disorders | alcoholic hepatitis | 3.E-10 | 5 | CXCL1,CXCL2,CXCL6,CXCL8,IL6 | ||
Cell Death and Survival | cell death of myeloid cells | 5.E-10 | 8 | BCL2A1,BIRC3,CXCL1,CXCL2,CXCL8,IL6,PMAIP1,TSLP | ||
E | Overlapping B and C | Connective Tissue Disorders, Organismal Injury and Abnormalities, Skeletal and Muscular Disorders, Skeletal and Muscular System Development and Function | abnormal morphology of skeleton | 1.E-05 | 4 | FMOD,ID1,KLF10,SFRP2 |
Cellular Function and Maintenance, Tissue Development | function of chondrocytes | 2.E-05 | 2 | FMOD,SFRP2 | ||
Connective Tissue Development and Function, Connective Tissue Disorders, Organ Morphology, Organismal Development, Organismal Injury and Abnormalities, Skeletal and Muscular Disorders, Skeletal and Muscular System Development and Function, Tissue Development | abnormal morphology of limb bone | 3.E-05 | 3 | FMOD,KLF10,SFRP2 | ||
Connective Tissue Development and Function, Skeletal and Muscular System Development and Function, Tissue Development | ossification of bone | 4.E-05 | 3 | FMOD,KLF10,SFRP2 | ||
Skeletal and Muscular System Development and Function | morphogenesis of skeletal system | 4.E-05 | 3 | CSRNP1,FMOD,SFRP2 | ||
Cancer, Cell Death and Survival, Organismal Injury and Abnormalities, Tumor Morphology | cell death of cancer cells | 6.E-05 | 4 | FMOD,KLF10,RPS16,SFRP2 | ||
Connective Tissue Development and Function, Skeletal and Muscular System Development and Function | strength of bone | 2.E-04 | 2 | ID1,KLF10 | ||
Cancer, Organismal Injury and Abnormalities | mucoepidermoid carcinoma | 2.E-04 | 2 | RPS16,SFRP2 | ||
Hematological Disease, Immunological Disease, Organismal Injury and Abnormalities | abnormality of bone marrow cells | 2.E-04 | 2 | GADD45B,ID1 | ||
Connective Tissue Development and Function, Skeletal and Muscular System Development and Function, Tissue Development | morphology of bone | 3.E-04 | 4 | FMOD,ID1,KLF10,SFRP2 |
상기 표 11에 나타낸 바와 같이, GO 분석과 비슷한 패턴을 나타내는 것을 확인하였다. 예를 들어, 젊은 GF의 차등 발현 유전자의 감염(세포 죽음, 및 세포 죽음, 세포 사멸 및 증식과 같은 생존 관련 기능)에 대한 반응에 있어서 생물학적 기능은 노화된 GF의 차등 발현 유전자의 감염(골격 및 골격의 형태학, 결합 조직 세포의 분화 및 골격의 비정상적인 형태와 같은 세포 발달 관련 기능)에 대한 기능과 구별되는 것을 확인하였다. 또한, F. n-감염 젊은 GF 및 노화된 GF 사이의 직접 비교에 의한 차등 발현 유전자는 세포 죽음 및 세포 죽음, 세포 사멸 및 괴사와 같은 생존 관련 기능을 나타내는 것을 확인하였다.
비슷한 맥락에서, 젊은 GF-특이적 차등 발현 유전자는 식도염, 골관절염 및 염증 반응과 같은 면역 반응에 관여하는 반면, 노화된 GF-특이적 차등 발현 유전자는 골격의 비정상 형태와 같은 결합 조직 장애 또는 발달, 및 사지 뼈의 비정상 형태에 관여하는 것으로 나타났다.
6. 차등 발현 유전자(
DEGs
)의 네트워크 분석
차등 발현된 유전자의 가능한 상호 작용을 확인하기 위하여, IPA를 사용하여 의해 젊은 GF-특이적 및 노화된 GF-특이적 차등 발현 유전자의 네트워크 분석을 수행하였다.
그 결과, 도 7에 나타낸 바와 같이, 젊은 GF-특이적 차등 발현 유전자는 위장병, 염증성 질환, 유기체 감염 및 비정상 경로(점수 33 및 집중 분자 13)의 네트워크와 밀접한 관련이 있었다. 즉, 노화된 GF와 비교하여 젊은 GF에서 이러한 차등 발현 유전자가 상향 조절되었고, 대다수의 유전자는 NF-kB 활성화 및 다양한 케모카인과 관련이 있었다.
또한, 노화된-GF 특이적 차등 발현 유전자는 자유 라디칼 소거, 세포주기 및 암 경로(점수 30 및 집중 분자 13)의 네트워크와 밀접한 관련이 있었다. 즉, 자유 라디칼 소거에 관여하는 유전자인 SOD3은 하향 조절되었지만, GADD45B, ID1, KLF10, CSRNP1 및 TM4SF1을 비롯한 세포주기 또는 암 관련 유전자는 젊은 GF와 비교하여 노화된 GF에서 상향 조절되었다.
나아가, 도 8에 나타낸 바와 같이, 젊은 GF에서 상향 조절된 차등 발현 유전자는 모두 핵과 세포질에 국한되어 있었으나, 노화된 GF에서 상향 조절된 차등 발현 유전자는 핵 내에 국한된 반면, 하향 조절된 차등 발현 유전자는 세포질에 국한되어 있는 것을 확인할 수 있었다.
상기 내용을 종합한 결과, 노화된 구강세포와 젊은 구강세포 모두에서 감염시 특이적으로 고발현되는 유전자군을 치주염 진단을 위하여 사용할 수 있을 것으로 기대되고, 특히, 노화된 구강세포에서 차별적으로 고발현되는 유전자군은 노인성 치주염 진단을 위하여 사용할 수 있을 것으로 기대된다.
<110> INDUSTRY FOUNDATION OF CHONNAM NATIONAL UNIVERSITY
<120> A biomarker for diagnosing periodontal disease
<130> 06048
<160> 62
<170> KopatentIn 2.0
<210> 1
<211> 1955
<212> RNA
<213> NM_002852.3 Homo sapiens pentraxin 3 (PTX3), mRNA
<400> 1
attcatcccc attcaggctt tcctcagcat ttattaagga ctctctgctc cagcctctca 60
ctctcactct cctccgctca aactcagctc acttgagagt ctcctcccgc cagctgtgga 120
aagaactttg cgtctctcca gcaatgcatc tccttgcgat tctgttttgt gctctctggt 180
ctgcagtgtt ggccgagaac tcggatgatt atgatctcat gtatgtgaat ttggacaacg 240
aaatagacaa tggactccat cccactgagg accccacgcc gtgcgcctgc ggtcaggagc 300
actcggaatg ggacaagctc ttcatcatgc tggagaactc gcagatgaga gagcgcatgc 360
tgctgcaagc cacggacgac gtcctgcggg gcgagctgca gaggctgcgg gaggagctgg 420
gccggctcgc ggaaagcctg gcgaggccgt gcgcgccggg ggctcccgca gaggccaggc 480
tgaccagtgc tctggacgag ctgctgcagg cgacccgcga cgcgggccgc aggctggcgc 540
gtatggaggg cgcggaggcg cagcgcccag aggaggcggg gcgcgccctg gccgcggtgc 600
tagaggagct gcggcagacg cgagccgacc tgcacgcggt gcagggctgg gctgcccgga 660
gctggctgcc ggcaggttgt gaaacagcta ttttattccc aatgcgttcc aagaagattt 720
ttggaagcgt gcatccagtg agaccaatga ggcttgagtc ttttagtgcc tgcatttggg 780
tcaaagccac agatgtatta aacaaaacca tcctgttttc ctatggcaca aagaggaatc 840
catatgaaat ccagctgtat ctcagctacc aatccatagt gtttgtggtg ggtggagagg 900
agaacaaact ggttgctgaa gccatggttt ccctgggaag gtggacccac ctgtgcggca 960
cctggaattc agaggaaggg ctcacatcct tgtgggtaaa tggtgaactg gcggctacca 1020
ctgttgagat ggccacaggt cacattgttc ctgagggagg aatcctgcag attggccaag 1080
aaaagaatgg ctgctgtgtg ggtggtggct ttgatgaaac attagccttc tctgggagac 1140
tcacaggctt caatatctgg gatagtgttc ttagcaatga agagataaga gagaccggag 1200
gagcagagtc ttgtcacatc cgggggaata ttgttgggtg gggagtcaca gagatccagc 1260
cacatggagg agctcagtat gtttcataaa tgttgtgaaa ctccacttga agccaaagaa 1320
agaaactcac acttaaaaca catgccagtt gggaaggtct gaaaactcag tgcataatag 1380
gaacacttga gactaatgaa agagagagtt gagaccaatc tttatttgta ctggccaaat 1440
actgaataaa cagttgaagg aaagacattg gaaaaagctt ttgaggataa tgttactaga 1500
ctttatgcca tggtgctttc agtttaatgc tgtgtctctg tcagataaac tctcaaataa 1560
ttaaaaagga ctgtattgtt gaacagaggg acaattgttt tacttttctt tggttaattt 1620
tgttttggcc agagatgaat tttacattgg aagaataaca aaataagatt tgttgtccat 1680
tgttcattgt tattggtatg taccttatta caaaaaaaag atgaaaacat atttatacta 1740
caaggtgact taacaactat aaatgtagtt tatgtgttat aatcgaatgt cacgtttttg 1800
agaagatagt catataagtt atattgcaaa agggatttgt attaatttaa gactattttt 1860
gtaaagctct actgtaaata aaatatttta taaaactagc tcacgtcatt taattataaa 1920
tttaagagat gttttggaaa aaaaaaaaaa aaaaa 1955
<210> 2
<211> 1184
<212> RNA
<213> NM_001511.3 Homo sapiens C-X-C motif chemokine ligand 1 (CXCL1), transcript variant 1, mRN
<400> 2
cacagagccc gggccgcagg cacctcctcg ccagctcttc cgctcctctc acagccgcca 60
gacccgcctg ctgagcccca tggcccgcgc tgctctctcc gccgccccca gcaatccccg 120
gctcctgcga gtggcactgc tgctcctgct cctggtagcc gctggccggc gcgcagcagg 180
agcgtccgtg gccactgaac tgcgctgcca gtgcttgcag accctgcagg gaattcaccc 240
caagaacatc caaagtgtga acgtgaagtc ccccggaccc cactgcgccc aaaccgaagt 300
catagccaca ctcaagaatg ggcggaaagc ttgcctcaat cctgcatccc ccatagttaa 360
gaaaatcatc gaaaagatgc tgaacagtga caaatccaac tgaccagaag ggaggaggaa 420
gctcactggt ggctgttcct gaaggaggcc ctgcccttat aggaacagaa gaggaaagag 480
agacacagct gcagaggcca cctggattgt gcctaatgtg tttgagcatc gcttaggaga 540
agtcttctat ttatttattt attcattagt tttgaagatt ctatgttaat attttaggtg 600
taaaataatt aagggtatga ttaactctac ctgcacactg tcctattata ttcattcttt 660
ttgaaatgtc aaccccaagt tagttcaatc tggattcata tttaatttga aggtagaatg 720
ttttcaaatg ttctccagtc attatgttaa tatttctgag gagcctgcaa catgccagcc 780
actgtgatag aggctggcgg atccaagcaa atggccaatg agatcattgt gaaggcaggg 840
gaatgtatgt gcacatctgt tttgtaactg tttagatgaa tgtcagttgt tatttattga 900
aatgatttca cagtgtgtgg tcaacatttc tcatgttgaa actttaagaa ctaaaatgtt 960
ctaaatatcc cttggacatt ttatgtcttt cttgtaaggc atactgcctt gtttaatggt 1020
agttttacag tgtttctggc ttagaacaaa ggggcttaat tattgatgtt ttcatagaga 1080
atataaaaat aaagcactta tagaaaaaac tcgtttgatt tttgggggga aacaagggct 1140
acctttactg gaaaatctgg tgatttataa aaaaaaaaaa aaaa 1184
<210> 3
<211> 1234
<212> RNA
<213> NM_002089.3 Homo sapiens C-X-C motif chemokine ligand 2 (CXCL2), mRNA
<400> 3
gagctccggg aatttccctg gcccgggact ccgggctttc cagccccaac catgcataaa 60
aggggttcgc cgttctcgga gagccacaga gcccgggcca caggcagctc cttgccagct 120
ctcctcctcg cacagccgct cgaaccgcct gctgagcccc atggcccgcg ccacgctctc 180
cgccgccccc agcaatcccc ggctcctgcg ggtggcgctg ctgctcctgc tcctggtggc 240
cgccagccgg cgcgcagcag gagcgcccct ggccactgaa ctgcgctgcc agtgcttgca 300
gaccctgcag ggaattcacc tcaagaacat ccaaagtgtg aaggtgaagt cccccggacc 360
ccactgcgcc caaaccgaag tcatagccac actcaagaat gggcagaaag cttgtctcaa 420
ccccgcatcg cccatggtta agaaaatcat cgaaaagatg ctgaaaaatg gcaaatccaa 480
ctgaccagaa ggaaggagga agcttattgg tggctgttcc tgaaggaggc cctgccctta 540
caggaacaga agaggaaaga gagacacagc tgcagaggcc acctggattg cgcctaatgt 600
gtttgagcat cacttaggag aagtcttcta tttatttatt tatttattta tttgtttgtt 660
ttagaagatt ctatgttaat attttatgtg taaaataagg ttatgattga atctacttgc 720
acactctccc attatattta ttgtttattt taggtcaaac ccaagttagt tcaatcctga 780
ttcatattta atttgaagat agaaggtttg cagatattct ctagtcattt gttaatattt 840
cttcgtgatg acatatcaca tgtcagccac tgtgatagag gctgaggaat ccaagaaaat 900
ggccagtgag atcaatgtga cggcagggaa atgtatgtgt gtctattttg taactgtaaa 960
gatgaatgtc agttgttatt tattgaaatg atttcacagt gtgtggtcaa catttctcat 1020
gttgaagctt taagaactaa aatgttctaa atatcccttg gacattttat gtctttcttg 1080
taaggcatac tgccttgttt aatgttaatt atgcagtgtt tccctctgtg ttagagcaga 1140
gaggtttcga tatttattga tgttttcaca aagaacagga aaataaaata tttaaaaata 1200
taaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaa 1234
<210> 4
<211> 4180
<212> RNA
<213> NM_006291.2 Homo sapiens TNF alpha induced protein 2 (TNFAIP2), mRNA
<400> 4
ccagggtgat gctgaagatg atgaccttct tccaaggcct ctagagccat cagcctgtgc 60
caggcaccct cgacttgcct agaggccccc aaaagttgca gtccacatca gaggcagagt 120
cagaggcctc catgtcggag gcctcctctg aggacctggt gccacccctg gaggctgggg 180
cagccccata tagggaggag gaagaggcgg cgaagaagaa gaaggagaag aagaagaagt 240
ccaaaggcct ggccaatgtg ttctgcgtct tcaccaaagg gaagaagaag aagggtcagc 300
ccagctcagc ggagcccgag gacgcagccg ggtccaggca ggggctggat ggcccgcccc 360
ccacagtgga ggagctgaag gcggcgctgg agcgcgggca gctggaggcg gcgcggccgc 420
tgctggcgct ggagcgggag ctggcggcgg cggcggcggc gggcggtgtg agcgaggagg 480
agctggtgcg gcgccagagc aaggtggagg cgctgtacga gctgctgcgc gaccaggtgc 540
tgggcgtgct gcggcggccg ctggaggcgc cgcccgagcg gctgcgccag gcgctggccg 600
tggtggcgga gcaggagcgc gaggaccgcc aggcggcggc ggcggggccg gggacctcgg 660
ggctggcggc cacgcgcccg cggcgctggc tgcagctgtg gcggcgcggc gtggcggagg 720
cggccgagga gcgcatgggc cagcggccgg ccgcgggcgc cgaggtcccc gagagcgtct 780
ttctgcactt gggccgcacc atgaaggagg acctggaggc cgtggtggag cggctgaagc 840
cgctgttccc cgccgagttc ggcgtcgtgg cggcctacgc cgagagctac caccagcact 900
tcgcggccca cctggccgcc gtggcgcagt tcgagctgtg cgagcgcgac acctacatgc 960
tgctgctctg ggtgcagaac ctctacccca atgacatcat caacagcccc aagctggtgg 1020
gtgagctgca gggtatgggg ctcgggagcc tcctgccccc caggcagatc cgactgctgg 1080
aggccacatt cctgtccagt gaggcggcca atgtgaggga gttgatggac cgagctctgg 1140
agctagaggc acggcgctgg gctgaggatg tgcctcccca gaggctggac ggccactgcc 1200
acagcgagct ggccatcgac atcatccaga tcacctccca ggcccaggcc aaggccgaga 1260
gcatcacgct ggacttgggc tcacagataa agcgggtgct gctggtggag ctgcctgcgt 1320
tcctgaggag ctaccagcgc gcctttaatg aatttctgga gagaggcaag cagctgacga 1380
attacagggc caatgttatt gccaacatca acaactgcct gtccttccgg atgtccatgg 1440
agcagaattg gcaggtaccc caggacaccc tgagcctcct gctgggcccc ctgggtgagc 1500
tcaagagcca cggctttgac accctgctcc agaacctgca tgaggacctg aagccactgt 1560
tcaagaggtt cacgcacacc cgctgggcgg cccctgtgga gaccctggaa aacatcatcg 1620
ccactgtaga cacgaggctg cctgagttct cagagctgca gggctgtttc cgggaggagc 1680
tcatggaggc cttgcacctg cacctggtga aggagtacat catccaactc agcaaggggc 1740
gcctggtcct caagacggcc gagcagcagc agcagctggc tgggtacatc ctggccaatg 1800
ctgacaccat ccagcacttc tgcacccagc acggctcccc ggcgacctgg ctgcagcctg 1860
ctctccctac gctggccgag atcattcgcc tgcaggaccc cagtgccatc aagattgagg 1920
tggccactta tgccacctgc taccctgact tcagcaaagg ccacctgagc gctatcctgg 1980
ccatcaaggg gaacctatcc aacagtgagg tcaagcgcat ccggagcatc ttggacgtca 2040
gcatgggggc gcaggagccc tcccggcccc tattttccct tataaaggtt ggttagcttt 2100
tcctgtggcc tgacctgcct gtgagtgccc agcaagcctt gggcacaccc cgctgggagc 2160
tgttaagagc agcgctggtt ctcggttcct cccgggtctc ctgtgctctg atgctacttc 2220
tgcctagccc tggcggaggt gcaggccctg tcagctggaa ctggacagac cttggtttgt 2280
ttacatgtcc gatgggggca ggagctccca tcctgggcag ccaaccaggc aacaccaagg 2340
actctttgta aacgatagct gatcgtgtgc acgcaaggaa agaaccagga gggagagtgc 2400
agccaggctc agggatcccc ggacacctct gtccagagcc cctccacagt cggcctcatg 2460
actgtcctcc tcgtgggtgg ggccgagggc cctcttcagc tctctggaga caggggccga 2520
gcctcaccca tctgccctct gcagcccagg gccgccgtga gcgggattca gcaatggtgg 2580
aatggaagac agaactggaa gagaaagaag gaaaagatga gctctcgtct ggcaggggct 2640
tttagggtcc tgtggcgagc tgtgagcacc gccagcatta gacgtcacat ccaggtggcc 2700
ccacggcccc tacaggctgg ccctgcaatg gggccctgag ccctccctct tcatccccca 2760
aggcctcaac tagagggtgg tcccccgagg gcttggtgtc tactaccgaa gggcccaaga 2820
cctcctgggt cctctcaggc tcccccttcc ccaaggcagg gacaggccct gggggtgcca 2880
ccgtgggccc tgccacccag aagtctggct gaggtctggg caggggcagg gcaagcttga 2940
cctctcactg ttgacccttt ggcctctgta tttgtttcct attgccgtga caggtttcca 3000
caaacttcgt ggatcaaaac gaggtcttcc agttctgcgg gtcagaaggc tgacccgggg 3060
ctcaaatctg ggtgtcggca gtcctgcact ccttctggag gctctagggg agaattcatt 3120
tctggccttt tcatttttag aggctgaccg taattcttga cttcaggctc ctccatcttc 3180
agagccagct gtgggtagtt gaatcttttt cccgtcacct cattgaggcc tcccctctcc 3240
tgcctccctc caccactttt tttttttttt ttttgagaca gggtcttgct gtgttgccca 3300
ggctggagtg cagtggcctg gtcatggcat caaggctcac tgcagcctgg acctcctggt 3360
tcaagtgatc ctcttgtctc agtcccctga gacaatcccc cacgcccagc tacatatttt 3420
ttgtggatac agggtctcat tctgttgcct aggcttgtct ggaactcctg ggctcaaggg 3480
atcttgtagc cttagcctcc taaagtgctg ggattatagg catgagtcac tgtacccggc 3540
ctgctctacc gcttttaagg acgcttatga tcacattgcg cctacccaga gaacccaggt 3600
cgtctttcta ttttcaggtc agctgattag ccaccttagt tccatctgca actttagttc 3660
ccactggctg tgtaacctaa catagtcaca ggctctgggg actgtcacgt ggacatcttt 3720
gggaggccgt tattctgccc accgcaccct ccgttcatcc cctgccctgc cgggcacctc 3780
gctctacccc aggaaaatgt gagctcgttt tcctgctcgg catgtgctcc ccctaaggct 3840
ctgctcctcc ctgggcctga aagttccttc tcagcctgag agggggccct tcggactcag 3900
gcatgactca gcccggctga tgcctctgca gtgctgagtc aggatttggg gccggctctc 3960
ttgggtccgt ccccttttcc caggtactgc cttacaaagc tgtggccagg aagtggccgg 4020
tataaaggat gcccaaggtc tttgtacgtg tgtaggagtt agcgtgtttg atattgttaa 4080
tataataata attatttttt agagtactgc ttttgtatgt atgttgaaca ggatccaggt 4140
ttttatagct tgatataaaa cagaattcaa aagtgaaaaa 4180
<210> 5
<211> 1718
<212> RNA
<213> NM_000584.3 Homo sapiens C-X-C motif chemokine ligand 8 (CXCL8, IL8), mRNA
<400> 5
gagggtgcat aagttctcta gtagggtgat gatataaaaa gccaccggag cactccataa 60
ggcacaaact ttcagagaca gcagagcaca caagcttcta ggacaagagc caggaagaaa 120
ccaccggaag gaaccatctc actgtgtgta aacatgactt ccaagctggc cgtggctctc 180
ttggcagcct tcctgatttc tgcagctctg tgtgaaggtg cagttttgcc aaggagtgct 240
aaagaactta gatgtcagtg cataaagaca tactccaaac ctttccaccc caaatttatc 300
aaagaactga gagtgattga gagtggacca cactgcgcca acacagaaat tattgtaaag 360
ctttctgatg gaagagagct ctgtctggac cccaaggaaa actgggtgca gagggttgtg 420
gagaagtttt tgaagagggc tgagaattca taaaaaaatt cattctctgt ggtatccaag 480
aatcagtgaa gatgccagtg aaacttcaag caaatctact tcaacacttc atgtattgtg 540
tgggtctgtt gtagggttgc cagatgcaat acaagattcc tggttaaatt tgaatttcag 600
taaacaatga atagtttttc attgtaccat gaaatatcca gaacatactt atatgtaaag 660
tattatttat ttgaatctac aaaaaacaac aaataatttt taaatataag gattttccta 720
gatattgcac gggagaatat acaaatagca aaattgaggc caagggccaa gagaatatcc 780
gaactttaat ttcaggaatt gaatgggttt gctagaatgt gatatttgaa gcatcacata 840
aaaatgatgg gacaataaat tttgccataa agtcaaattt agctggaaat cctggatttt 900
tttctgttaa atctggcaac cctagtctgc tagccaggat ccacaagtcc ttgttccact 960
gtgccttggt ttctccttta tttctaagtg gaaaaagtat tagccaccat cttacctcac 1020
agtgatgttg tgaggacatg tggaagcact ttaagttttt tcatcataac ataaattatt 1080
ttcaagtgta acttattaac ctatttatta tttatgtatt tatttaagca tcaaatattt 1140
gtgcaagaat ttggaaaaat agaagatgaa tcattgattg aatagttata aagatgttat 1200
agtaaattta ttttatttta gatattaaat gatgttttat tagataaatt tcaatcaggg 1260
tttttagatt aaacaaacaa acaattgggt acccagttaa attttcattt cagataaaca 1320
acaaataatt ttttagtata agtacattat tgtttatctg aaattttaat tgaactaaca 1380
atcctagttt gatactccca gtcttgtcat tgccagctgt gttggtagtg ctgtgttgaa 1440
ttacggaata atgagttaga actattaaaa cagccaaaac tccacagtca atattagtaa 1500
tttcttgctg gttgaaactt gtttattatg tacaaataga ttcttataat attatttaaa 1560
tgactgcatt tttaaataca aggctttata tttttaactt taagatgttt ttatgtgctc 1620
tccaaatttt ttttactgtt tctgattgta tggaaatata aaagtaaata tgaaacattt 1680
aaaatataat ttgttgtcaa agtaaaaaaa aaaaaaaa 1718
<210> 6
<211> 1197
<212> RNA
<213> NM_000600.4 Homo sapiens interleukin 6 (IL6), transcript variant 1, mRNA
<400> 6
gtctcaatat tagagtctca acccccaata aatataggac tggagatgtc tgaggctcat 60
tctgccctcg agcccaccgg gaacgaaaga gaagctctat ctcccctcca ggagcccagc 120
tatgaactcc ttctccacaa gcgccttcgg tccagttgcc ttctccctgg ggctgctcct 180
ggtgttgcct gctgccttcc ctgccccagt acccccagga gaagattcca aagatgtagc 240
cgccccacac agacagccac tcacctcttc agaacgaatt gacaaacaaa ttcggtacat 300
cctcgacggc atctcagccc tgagaaagga gacatgtaac aagagtaaca tgtgtgaaag 360
cagcaaagag gcactggcag aaaacaacct gaaccttcca aagatggctg aaaaagatgg 420
atgcttccaa tctggattca atgaggagac ttgcctggtg aaaatcatca ctggtctttt 480
ggagtttgag gtatacctag agtacctcca gaacagattt gagagtagtg aggaacaagc 540
cagagctgtg cagatgagta caaaagtcct gatccagttc ctgcagaaaa aggcaaagaa 600
tctagatgca ataaccaccc ctgacccaac cacaaatgcc agcctgctga cgaagctgca 660
ggcacagaac cagtggctgc aggacatgac aactcatctc attctgcgca gctttaagga 720
gttcctgcag tccagcctga gggctcttcg gcaaatgtag catgggcacc tcagattgtt 780
gttgttaatg ggcattcctt cttctggtca gaaacctgtc cactgggcac agaacttatg 840
ttgttctcta tggagaacta aaagtatgag cgttaggaca ctattttaat tatttttaat 900
ttattaatat ttaaatatgt gaagctgagt taatttatgt aagtcatatt tatattttta 960
agaagtacca cttgaaacat tttatgtatt agttttgaaa taataatgga aagtggctat 1020
gcagtttgaa tatcctttgt ttcagagcca gatcatttct tggaaagtgt aggcttacct 1080
caaataaatg gctaacttat acatattttt aaagaaatat ttatattgta tttatataat 1140
gtataaatgg tttttatacc aataaatggc attttaaaaa attcagcaaa aaaaaaa 1197
<210> 7
<211> 4093
<212> RNA
<213> NM_003998.3 Homo sapiens nuclear factor kappa B subunit 1 (NFKB1)
<400> 7
gtgagagagt gagcgagaca gaaagagaga gaagtgcacc agcgagccgg ggcaggaaga 60
ggaggtttcg ccaccggagc ggcccggcga cgcgctgaca gcttcccctg cccttcccgt 120
cggtcgggcc gccagccgcc gcagccctcg gcctgcacgc agccaccggc cccgctcccg 180
gagcccagcg ccgccgaggc cgcagccgcc cggccagtaa ggcggcgccg ccgcccggcc 240
accgcgcgcc ctgcgcttcc ctccgcccgc gctgcggcca tggcgcggcg ctgactggcc 300
tggcccggcc ccgccgcgct cccgctcgcc ccgacccgca ctcgggcccg cccgggctcc 360
ggcctgccgc cgcctcttcc ttctccagcc ggcaggcccg cgccgcttag gagggagagc 420
ccacccgcgc caggaggccg aacgcggact cgccacccgg cttcagaatg gcagaagatg 480
atccatattt gggaaggcct gaacaaatgt ttcatttgga tccttctttg actcatacaa 540
tatttaatcc agaagtattt caaccacaga tggcactgcc aacagcagat ggcccatacc 600
ttcaaatatt agagcaacct aaacagagag gatttcgttt ccgttatgta tgtgaaggcc 660
catcccatgg tggactacct ggtgcctcta gtgaaaagaa caagaagtct taccctcagg 720
tcaaaatctg caactatgtg ggaccagcaa aggttattgt tcagttggtc acaaatggaa 780
aaaatatcca cctgcatgcc cacagcctgg tgggaaaaca ctgtgaggat gggatctgca 840
ctgtaactgc tggacccaag gacatggtgg tcggcttcgc aaacctgggt atacttcatg 900
tgacaaagaa aaaagtattt gaaacactgg aagcacgaat gacagaggcg tgtataaggg 960
gctataatcc tggactcttg gtgcaccctg accttgccta tttgcaagca gaaggtggag 1020
gggaccggca gctgggagat cgggaaaaag agctaatccg ccaagcagct ctgcagcaga 1080
ccaaggagat ggacctcagc gtggtgcggc tcatgtttac agcttttctt ccggatagca 1140
ctggcagctt cacaaggcgc ctggaacccg tggtatcaga cgccatctat gacagtaaag 1200
cccccaatgc atccaacttg aaaattgtaa gaatggacag gacagctgga tgtgtgactg 1260
gaggggagga aatttatctt ctttgtgaca aagttcagaa agatgacatc cagattcgat 1320
tttatgaaga ggaagaaaat ggtggagtct gggaaggatt tggagatttt tcccccacag 1380
atgttcatag acaatttgcc attgtcttca aaactccaaa gtataaagat attaatatta 1440
caaaaccagc ctctgtgttt gtccagcttc ggaggaaatc tgacttggaa actagtgaac 1500
caaaaccttt cctctactat cctgaaatca aagataaaga agaagtgcag aggaaacgtc 1560
agaagctcat gcccaatttt tcggatagtt tcggcggtgg tagtggtgct ggagctggag 1620
gcggaggcat gtttggtagt ggcggtggag gagggggcac tggaagtaca ggtccagggt 1680
atagcttccc acactatgga tttcctactt atggtgggat tactttccat cctggaacta 1740
ctaaatctaa tgctgggatg aagcatggaa ccatggacac tgaatctaaa aaggaccctg 1800
aaggttgtga caaaagtgat gacaaaaaca ctgtaaacct ctttgggaaa gttattgaaa 1860
ccacagagca agatcaggag cccagcgagg ccaccgttgg gaatggtgag gtcactctaa 1920
cgtatgcaac aggaacaaaa gaagagagtg ctggagttca ggataacctc tttctagaga 1980
aggctatgca gcttgcaaag aggcatgcca atgccctttt cgactacgcg gtgacaggag 2040
acgtgaagat gctgctggcc gtccagcgcc atctcactgc tgtgcaggat gagaatgggg 2100
acagtgtctt acacttagca atcatccacc ttcattctca acttgtgagg gatctactag 2160
aagtcacatc tggtttgatt tctgatgaca ttatcaacat gagaaatgat ctgtaccaga 2220
cgcccttgca cttggcagtg atcactaagc aggaagatgt ggtggaggat ttgctgaggg 2280
ctggggccga cctgagcctt ctggaccgct tgggtaactc tgttttgcac ctagctgcca 2340
aagaaggaca tgataaagtt ctcagtatct tactcaagca caaaaaggca gcactacttc 2400
ttgaccaccc caacggggac ggtctgaatg ccattcatct agccatgatg agcaatagcc 2460
tgccatgttt gctgctgctg gtggccgctg gggctgacgt caatgctcag gagcagaagt 2520
ccgggcgcac agcactgcac ctggctgtgg agcacgacaa catctcattg gcaggctgcc 2580
tgctcctgga gggtgatgcc catgtggaca gtactaccta cgatggaacc acacccctgc 2640
atatagcagc tgggagaggg tccaccaggc tggcagctct tctcaaagca gcaggagcag 2700
atcccctggt ggagaacttt gagcctctct atgacctgga tgactcttgg gaaaatgcag 2760
gagaggatga aggagttgtg cctggaacca cgcctctaga tatggccacc agctggcagg 2820
tatttgacat attaaatggg aaaccatatg agccagagtt tacatctgat gatttactag 2880
cacaaggaga catgaaacag ctggctgaag atgtgaagct gcagctgtat aagttactag 2940
aaattcctga tccagacaaa aactgggcta ctctggcgca gaaattaggt ctggggatac 3000
ttaataatgc cttccggctg agtcctgctc cttccaaaac acttatggac aactatgagg 3060
tctctggggg tacagtcaga gagctggtgg aggccctgag acaaatgggc tacaccgaag 3120
caattgaagt gatccaggca gcctccagcc cagtgaagac cacctctcag gcccactcgc 3180
tgcctctctc gcctgcctcc acaaggcagc aaatagacga gctccgagac agtgacagtg 3240
tctgcgacag cggcgtggag acatccttcc gcaaactcag ctttaccgag tctctgacca 3300
gtggtgcctc actgctaact ctcaacaaaa tgccccatga ttatgggcag gaaggacctc 3360
tagaaggcaa aatttagcct gctgacaatt tcccacaccg tgtaaaccaa agccctaaaa 3420
ttccactgcg ttgtccacaa gacagaagct gaagtgcatc caaaggtgct cagagagccg 3480
gcccgcctga atcattctcg atttaactcg agaccttttc aacttggctt cctttcttgg 3540
ttcataaatg aattttagtt tggttcactt acagatagta tctagcaatc acaacactgg 3600
ctgagcggat gcatctgggg atgaggttgc ttactaagct ttgccagctg ctgctggatc 3660
acagctgctt tctgttgtca ttgctgttgt ccctctgcta cgttcctatt gtcattaaag 3720
gtatcacggt cgccacctgg cattccttct gaccacagca tcattttgca ttcaaattaa 3780
gggttaagaa aagagatatt ttaaaatgag agtcacttga tgtgccattt taaaaaaaaa 3840
ggcatattgc tttttctaat gtggttattt ctctgatttg caaaaaaaaa aaaaaaaaaa 3900
atacttgtca atatttaaac atggttacaa tcattgctga aaatggtatt ttcccccttt 3960
tctgcatttt gctattgtaa atatgttttt tagatcaaat actttaaagg aaaaaatgtt 4020
ggatttataa atgctatttt ttattttact tttataataa aaggaaaagc aaattgatga 4080
cctcaaaaaa aaa 4093
<210> 8
<211> 978
<212> RNA
<213> NM_015714.3 Homo sapiens G0/G1 switch 2 (G0S2), mRNA
<400> 8
tggctctgac cgcgctggcc tgggccggag agcccaggag gcgtgtctca gagaaaagat 60
ataagcggcc cccggacgct aaagcggtgc cagcggcgga gtctccaact gggagagctg 120
cagctgccga gaggaggaga acgctgaggt cggtcggacc aacggacgcg ctgaccgctg 180
ccaactgcag ctcgcgctgc ctcctgctcg cgccgtgcca ctaaggtcat tcccgcctcc 240
gagagcccag agccgagatg gaaacggtcc aggagctgat ccccctggcc aaggagatga 300
tggcccagaa gcgcaagggg aagatggtga agctgtacgt gctgggcagc gtgctggccc 360
tcttcggcgt ggtgctcggc ctgatggaga ctgtgtgcag ccccttcacg gccgccagac 420
gtctgcggga ccaggaggca gccgtggcgg agctgcaggc cgccctggag cgacaggctc 480
tccagaagca agccctgcag gagaaaggca agcagcagga cacggtcctc ggcggccggg 540
ccctgtccaa ccggcagcac gcctcctagg aactgtggga gaccagcgga gtgggaggga 600
gacgcagtag acagagacag accgagagag gaatggagag acagaggggg cgcgcgcaca 660
ggagcctgac tccgctggga gagtgcagga gcacgtgctg ttttttattt ggacttaact 720
tcagagaaac cgctgacatc tagaactgac ctaccacaag catccaccaa aggagtttgg 780
gattgagttt tgctgctgtg cagcactgca ttgtcatgac atttccaaca ctgtgtgaat 840
tatctaaatg cgtctaccat tttgcactag ggaggaagga taaatgcttt ttatgttatt 900
attattaatt attacaatga ccaccatttt gcattttgaa ataaaaaaac tttttatacc 960
ataaaaaaaa aaaaaaaa 978
<210> 9
<211> 3024
<212> RNA
<213> BC015969.2 Homo sapiens intercellular adhesion molecule 1, mRNA (ICM1)
<400> 9
ctataaagga tcacgcgccc cagtcgacgc tgagctcctc tgctactcag agttgcaacc 60
tcagcctcgc tatggctccc agcagccccc ggcccgcgct gcccgcactc ctggtcctgc 120
tcggggctct gttcccagga cctggcaatg cccagacatc tgtgtccccc tcaaaagtca 180
tcctgccccg gggaggctcc gtgctggtga catgcagcac ctcctgtgac cagcccaagt 240
tgttgggcat agagaccccg ttgcctaaaa aggagttgct cctgcctggg aacaaccgga 300
aggtgtatga actgagcaat gtgcaagaag atagccaacc aatgtgctat tcaaactgcc 360
ctgatgggca gtcaacagct aaaaccttcc tcaccgtgta ctggactcca gaacgggtgg 420
aactggcacc cctcccctct tggcagccag tgggcaagaa ccttacccta cgctgccagg 480
tggagggtgg ggcaccccgg gccaacctca ccgtggtgct gctccgtggg gagaaggagc 540
tgaaacggga gccagctgtg ggggagcccg ctgaggtcac gaccacggtg ctggtgagga 600
gagatcacca tggagccaat ttctcgtgcc gcactgaact ggacctgcgg ccccaagggc 660
tggagctgtt tgagaacacc tcggccccct accagctcca gacctttgtc ctgccagcga 720
ctcccccaca acttgtcagc ccccgggtcc tagaggtgga cacgcagggg accgtggtct 780
gttccctgga cgggctgttc ccagtctcgg aggcccaggt ccacctggca ctgggggacc 840
agaggttgaa ccccacagtc acctatggca acgactcctt ctcggccaag gcctcagtca 900
gtgtgaccgc agaggacgag ggcacccagc ggctgacgtg tgcagtaata ctggggaacc 960
agagccagga gacactgcag acagtgacca tctacagctt tccggcgccc aacgtgattc 1020
tgacgaagcc agaggtctca gaagggaccg aggtgacagt gaagtgtgag gcccacccta 1080
gagccaaggt gacgctgaat ggggttccag cccagccact gggcccgagg gcccagctcc 1140
tgctgaaggc caccccagag gacaacgggc gcagcttctc ctgctctgca accctggagg 1200
tggccggcca gcttatacac aagaaccaga cccgggagct tcgtgtcctg tatggccccc 1260
gactggacga gagggattgt ccgggaaact ggacgtggcc agaaaattcc cagcagactc 1320
caatgtgcca ggcttggggg aacccattgc ccgagctcaa gtgtctaaag gatggcactt 1380
tcccactgcc catcggggaa tcagtgactg tcactcgaga tcttgagggc acctacctct 1440
gtcgggccag gagcactcaa ggggaggtca cccgcaaggt gaccgtgaat gtgctctccc 1500
cccggtatga gattgtcatc atcactgtgg tagcagccgc agtcataatg ggcactgcag 1560
gcctcagcac gtacctctat aaccgccagc ggaagatcaa gaaatacaga ctacaacagg 1620
cccaaaaagg gacccccatg aaaccgaaca cacaagccac gcctccctga acctatcccg 1680
ggacagggcc tcttcctcgg ccttcccata ttggtggcag tggtgccaca ctgaacagag 1740
tggaagacat atgccatgca gctacaccta ccggccctgg gacgccggag gacagggcat 1800
tgtcctcagt cagatacaac agcatttggg gccatggtac ctgcacacct aaaacactag 1860
gccacgcatc tgatctgtag tcacatgact aagccaagag gaaggagcaa gactcaagac 1920
atgattgatg gatgttaaag tctagcctga tgagagggga agtggtgggg gagacatagc 1980
cccaccatga ggacatacaa ctgggaaata ctgaaacttg ctgcctattg ggtatgctga 2040
ggccccacag acttacagaa gaagtggccc tccatagaca tgtgtagcat caaaacacaa 2100
aggcccacac ttcctgacgg atgccagctt gggcactgct gtctactgac cccaaccctt 2160
gatgatatgt atttattcat ttgttatttt accagctatt tattgagtgt cttttatgta 2220
ggctaaatga acataggtct ctggcctcac ggagctccca gtcctaatca cattcaaggt 2280
caccaggtac agttgtacag gttgtacact gcaggagagt gcctggcaaa aagatcaaat 2340
ggggctggga cttctcattg gccaacctgc ctttccccag aaggagtgat ttttctatcg 2400
gcacaaaagc actatatgga ctggtaatgg ttacaggttc agagattacc cagtgaggcc 2460
ttattcctcc cttcccccca aaactgacac ctttgttagc cacctcccca cccacataca 2520
tttctgccag tgttcacaat gacactcagc ggtcatgtct ggacatgagt gcccagggaa 2580
tatgcccaag ctatgccttg tcctcttgtc ctgtttgcat ttcactggga gcttgcacta 2640
tgcagctcca gtttcctgca gtgatcaggg tcctgcaagc agtggggaag ggggccaagg 2700
tattggagga ctccctccca gctttggaag cctcatccgc gtgtgtgtgt gtgtgtatgt 2760
gtagacaagc tctcgctctg tcacccaggc tggagtgcag tggtgcaatc atggttcact 2820
gcagtcttga ccttttgagc tcaagtgatc ctcccacctc agcctcctga gtagctggga 2880
ccataggctc acaacaccac acctggcaaa tttgattttt tttttttttc cagagacggg 2940
gtcttgcaac attgcccaga cttcctttgt gttagttaat aaagctttct caactgccaa 3000
aaaaaaaaaa aaaaaaaaaa aaaa 3024
<210> 10
<211> 1051
<212> RNA
<213> BC003097.1 Homo sapiens intercellular adhesion molecule 2, mRNA (ICM2)
<400> 10
ctccctccag gcagcccttg gctggtccct gcgagcccgt ggagactgcc agagatgtcc 60
tctttcggtt acaggaccct gactgtggcc ctcttcaccc tgatctgctg tccaggatcg 120
gatgagaagg tattcgaggt acacgtgagg ccaaagaagc tggcggttga gcccaaaggg 180
tccctcgagg tcaactgcag caccacctgt aaccagcctg aagtgggtgg tctggagacc 240
tctctagata agattctgct ggacgaacag gctcagtgga aacattactt ggtctcaaac 300
atctcccatg acacggtcct ccaatgccac ttcacctgct ccgggaagca ggagtcaatg 360
aattccaacg tcagcgtgta ccagcctcca aggcaggtca tcctgacact gcaacccact 420
ttggtggctg tgggcaagtc cttcaccatt gagtgcaggg tgcccaccgt ggagcccctg 480
gacagcctca ccctcttcct gttccgtggc aatgagactc tgcactatga gaccttcggg 540
aaggcagccc ctgctccgca ggaggccaca gccacattca acagcacggc tgacagagag 600
gatggccacc gcaacttctc ctgcctggct gtgctggact tgatgtctcg cggtggcaac 660
atctttcaca aacactcagc cccgaagatg ttggagatct atgagcctgt gtcggacagc 720
cagatggtca tcatagtcac ggtggtgtcg gtgttgctgt ccctgttcgt gacatctgtc 780
ctgctctgct tcatcttcgg ccagcacttg cgccagcagc ggatgggcac ctacggggtg 840
cgagcggctt ggaggaggct gccccaggcc ttccggccat agcaaccatg agtggcatgg 900
ccaccaccac ggtggtcact ggaactcagt gtgactcctc agggttgagg tccagccctg 960
gctgaaggac tgtgacaggc agcagagact tgggacattg ccttttctag cccgaataca 1020
aacacctgga cttaaaaaaa aaaaaaaaaa a 1051
<210> 11
<211> 1771
<212> RNA
<213> BC058903.1 Homo sapiens intercellular adhesion molecule 3, mRNA (ICM3)
<400> 11
gtcagaatgg ccaccatggt accatccgtg ttgtggccca gggcctgctg gactctgctg 60
gtctgctgtc tgctgacccc aggtgtccag gggcaggagt tccttttgcg ggtggagccc 120
cagaaccctg tgctctctgc tggagggtcc ctgtttgtga actgcagtac tgattgtccc 180
agctctgaga aaatcgcctt ggagacgtcc ctatcaaagg agctggtggc cagtggcatg 240
ggctgggcag ccttcaatct cagcaacgtg actggcaaca gtcggatcct ctgctcagtg 300
tactgcaatg gctcccagat aacaggctcc tctaacatca ccgtgtacag gctcccggag 360
cgtgtggagc tggcacccct gcctccttgg cagccggtgg gccagaactt caccctgcgc 420
tgccaagtgg aggatgggtc gccccggacc agcctcacgg tggtgctgct tcgctgggag 480
gaggagctga gccggcagcc cgcagtggag gagccagcgg aggtcactgc cactgtgctg 540
gccagcagag acgaccacgg agcccctttc tcatgccgca cagaactgga catgcagccc 600
caggggctgg gactgttcgt gaacacctca gccccccgcc agctccgaac ctttgtcctg 660
cccgtgaccc ccccgcgcct cgtggccccc cggttcttgg aggtggaaac gtcgtggccg 720
gtggactgca ccctagacgg gctttttcca gcctcagagg cccaggtcta cctggcgctg 780
ggggaccaga tgctgaatgc gacagtcatg aaccacgggg acacgctaac ggccacagcc 840
acagccacgg cgcgcgcgga tcaggagggt gcccgggaga tcgtctgcaa cgtgacccta 900
gggggcgaga gacgggaggc ccgggagaac ttgacggtct ttagcttcct aggacccatt 960
gtgaacctca gcgagcccac cgcccatgag gggtccacag tgaccgtgag ttgcatggct 1020
ggggctcgag tccaggtcac gctggacgga gttccggccg cggccccggg gcagccagct 1080
caacttcagc taaatgctac cgagagtgac gacggacgca gcttcttctg cagtgccact 1140
ctcgaggtgg acggcgagtt cttgcacagg aacagtagcg tccagctgcg agtcctgtat 1200
ggtcccaaaa ttgaccgagc cacatgcccc cagcacttga aatggaaaga taaaacgaga 1260
cacgtcctgc agtgccaagc caggggcaac ccgtaccccg agctgcggtg tttgaaggaa 1320
ggctccagcc gggaggtgcc ggtggggatc ccgttcttcg tcaacgtaac acataatggt 1380
acttatcagt gccaagcgtc cagctcacga ggcaaataca ccctggtcgt ggtgatggac 1440
attgaggctg ggagctccca ctttgtcccc gtcttcgtgg cggtgttact gaccctgggc 1500
gtggtgacta tcgtactggc cttaatgtac gtcttcaggg agcaccaacg gagcggcagt 1560
taccatgtta gggaggagag cacctatctg cccctcacgt ctatgcagcc gacagaagca 1620
atgggggaag aaccgtccag agctgagtga cgctgggatc cgggatcaaa gttggcgggg 1680
gcttggctgt gccctcagat tccgcaccaa taaagccttc aaactcccta aaaaaaaaaa 1740
aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa a 1771
<210> 12
<211> 1846
<212> RNA
<213> BC008280.1 Homo sapiens prostaglandin E synthase, mRNA (PTGES)
<400> 12
tgatcacacc cacagttgag ctgcgctggc cagagatgcc tgcccacagc ctggtgatga 60
gcagcccggc cctcccggcc ttcctgctct gcagcacgct gctggtcatc aagatgtacg 120
tggtggccat catcacgggc caagtgaggc tgcggaagaa ggcctttgcc aaccccgagg 180
atgccctgag acacggaggc ccccagtatt gcaggagcga ccccgacgtg gaacgctgcc 240
tcagggccca ccggaacgac atggagacca tctacccctt ccttttcctg ggcttcgtct 300
actcctttct gggtcctaac ccttttgtcg cctggatgca cttcctggtc ttcctcgtgg 360
gccgtgtggc acacaccgtg gcctacctgg ggaagctgcg ggcacccatc cgctccgtga 420
cctacaccct ggcccagctc ccctgcgcct ccatggctct gcagatcctc tgggaagcgg 480
cccgccacct gtgaccagca gctgatgcct ccttggccac cagaccatgg gccaagagcc 540
gccgtggcta tacctgggga cttgatgttc cttccagatt gtggtgggcc ctgagtcctg 600
gtttcctggc agcctgctgc gcgtgtgggt ctctgggcac agtgggcctg tgtgtgtgcc 660
cgtgtgtgtg tatgtgtatg tgtgtgtgta tgtttcttag ccccttggat tcctgcacga 720
agtggctgat gggaaccatt tcaagacaga ttgtgaagat tgatagaaaa tccttcagct 780
aaagtaacag agcatcaaaa acatcactcc ctctccctcc ctaacagtga aaagagagaa 840
gggagactct atttaagatt cccaaaccta atgatcatct gaatcccggg ctaagaatgc 900
agacttttca gactgacccc agaaattctg gcccagccaa tctagaggca agcctggcca 960
tctgtatttt tttttttcca agacagagtc ttgctctgtt gcccaagctg gagtgaagtg 1020
gtacaatctg gctcactgca gcctccgcct cccgggttca agcgattctc ccgcctcagc 1080
ctcctgagta gctgggatta caggcgcgta tcaccatacc cagctaattt ttgtattttt 1140
agtagagacg ggttcaccat gttgcccagg agggtctcga actcctggcc tcaagtgatc 1200
caccggcctc ggcctcccaa agtgctggga tgacaggcat gaatcactgt gctcagccac 1260
catctggagt tttaaaaggc tcccatgtga gtccctgtga tggccaggcc aggggacccc 1320
tgccagttct ctgtggaagc aaggctgggg tcttgggttc ctgtatggtg gaagctgggt 1380
gagccaagga cagggctggc tcctctgccc ccgctgacgc ttcccttgcc gttggctttg 1440
gatgtctttg ctgcagtctt ctctctggct caggtgtggg tgggaggggc ccacaggaag 1500
ctcagccttc tcctcccaag gtttgagtcc ctccaaaggg cagtgggtgg aggaccggga 1560
gctttgggtg accagccact caaaggaact ttctggtccc ttcagtatct tcaaggtttg 1620
gaaactgcaa atgtcccctt gatggggaat ccgtgtgtgt gtgtgtgtgt gtgtgtgtgt 1680
gtgtgtgtgt gtgtgttttc tcctagaccc gtgacctgag atgtgtgatt tttagtcatt 1740
aaatggaagt gtctgccaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 1800
aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaa 1846
<210> 13
<211> 1283
<212> RNA
<213> BC032663.1 Homo sapiens phorbol-12-myristate-13-acetate-induced protein 1, mRNA (PMAIP1)
<400> 13
ccacgcgtcc gcgtgtgtag ttggcatctc cgcgcgtccg gacacccgat cccagcatcc 60
ctgcctgcag gactgttcgt gttcagctcg cgtcctgcag ctgtccgagg tgctccagtt 120
ggaggctgag gttcccgggc tctgtagctg agtgggcggc ggcaccggcg gagatgcctg 180
ggaagaaggc gcgcaagaac gctcaaccga gccccgcgcg ggctccagca ggaccggcgg 240
gtacggcggg tacggcgagg gaccaagccg gatttgcgat tgggatgcag ctgcgtttca 300
ccaggggcaa aaagctcctt tcctcctctc tttcctcctc gccacttgcc cttccccggg 360
gccacgagga acaagtgcaa gtagctggaa gtcgagtgtg ctactcaact caggagattt 420
ggagacaaac tgaacttccg gcagaaactt ctgaatctga tatccaaact cttctgctca 480
ggaacctgac tgcatcaaaa acttgcatga ggggactcct tcaaaagagt tttctcagga 540
ggtgcacgtt tcatcaattt gaagaaagac tgcattgtaa ttgagaggaa tgtgaaggtg 600
cattcatggg tgcccttgga aacggaagat ggaatacatc aaagtgaatt tctgttcaag 660
ttttcccaga ttatcattct ttgggatgag agaacattat aaaaccactt tgtttatttt 720
aaagcaagaa tggaagaccc ttgaaaataa agaagtaatt attgacacat ttctttttta 780
cttagagaat cgttctagtg tttttgccga agattaccgc tggcctactg tgaagggaga 840
tgacctgtga ttagactggg cggctgggga gaaacagttc agtgcattgt tgttgttgct 900
gtttttggtg ttttgctttt cagtgccaac tcagcacatt gtatatgatt cggtttatac 960
atattacctt gttataatga aaaaactcat tctgagaaca ctgaaatgtt atactcagtg 1020
ttgatttctt cggtcactac acaacgtaaa atcatttgtt tcttttgact caaattgtat 1080
tgcttctgtt cagatgatct ttcattcaat gtgttcctgt tgggcgttac tagaaactat 1140
ggaaaactgg aaaataactt tgaaaaaatt ggataaagta taggagggtt acttggggcc 1200
agtaaatcag tagactgaac attcaatata ataaaagaac atggggattt tgtataacca 1260
gggataataa aaaaaaaaaa aaa 1283
<210> 14
<211> 1984
<212> RNA
<213> BC000669.2 Homo sapiens spermine oxidase, mRNA (SMOX)
<400> 14
gtcccggcgg cggctggagg aggaagccag gcggctggcg gaggaggaga gacggaggag 60
gccgagaccg gagcgccgct cgccgcagac ttacttcccc ggctcagcag ggaaaggttc 120
ctagaaggtg agcgcggacg gtatgcaaag ttgtgaatcc agtggtgaca gtgcggatga 180
ccctctcagt cgcggcctac ggagaagggg acagcctcgt gtggtggtga tcggcgccgg 240
cttggctggc ctggctgcag ccaaagcact tcttgagcag ggtttcacgg atgtcactgt 300
gcttgaggct tccagccaca tcggaggccg tgtgcagagt gtgaaacttg gacacgccac 360
ctttgagctg ggagccacct ggatccatgg ctcccatggg aaccctatct atcatctagc 420
agaagccaac ggcctcctgg aagagacaac cgatggggaa cgcagcgtgg gccgcatcag 480
cctctattcc aagaatggcg tggcctgcta ccttaccaac cacggccgca ggatccccaa 540
ggacgtggtt gaggaattca gcgatttata caacgaggtc tataacttga cccaggagtt 600
cttccggcac gataaaccag tcaatgctga aagtcaaaat agcgtggggg tgttcacccg 660
agaggaggtg cgtaaccgca tcaggaatga ccctgacgac ccagaggcta ccaagcgcct 720
gaagctcgcc atgatccagc agtacctgaa ggtggagagc tgtgagagca gctcacacag 780
catggacgag gtgtccctga gcgccttcgg ggagtggacc gagatccccg gcgctcacca 840
catcatcccc tcgggcttca tgcgggttgt ggagctgctg gcggagggca tccctgccca 900
cgtcatccag ctagggaaac ctgtccgctg cattcactgg gaccaggcct cagcccgccc 960
cagaggccct gagattgagc cccggggtgt gctaaagagg cagtacacca gtttcttccg 1020
gccaggcctg cccacagaga aggtggctgc catccaccgc ctgggcattg gcaccaccga 1080
caagatcttt ctggaattcg aggagccctt ctggggccct gagtgcaaca gcctacagtt 1140
tgtgtgggag gacgaagcgg agagccacac cctcacctac ccacctgagc tctggtaccg 1200
caagatctgc ggctttgatg tcctctaccc gcctgagcgc tacggccatg tgctgagcgg 1260
ctggatctgc ggggaggagg ccctcgtcat ggagaagtgt gatgacgagg cagtggccga 1320
gatctgcacg gagatgctgc gtcagttcac agggaacccc aacattccaa aacctcggcg 1380
aatcttgcgc tcggcctggg gcagcaaccc ttacttccgc ggctcctatt catacacgca 1440
ggtgggctcc agcggggcgg atgtggagaa gctggccaag cccctgccgt acacggagag 1500
ctcaaagaca gcgcccatgc aggtgctgtt ttccggtgag gccacccacc gcaagtacta 1560
ttccaccacc cacggtgctc tgctgtccgg ccagcgtgag gctgcccgcc tcattgagat 1620
gtaccgagac ctcttccagc aggggacctg agggctgtcc tcgctgctga gaagagccac 1680
taactcgtga cctccagcct gccccttgct gccgtgtgct cctgccttcc tgatcctctg 1740
tagaaaggat ttttatcttc tgtagagcta gccgccctga ctgccttcag acctggccct 1800
gtagcttttc tttttctcca ggctgggccg tgagcaggtg ggccgttgag ttacctctgt 1860
gctggatccc gtgcccccac ttgcctaccc tctgtcctgc cttgttattg taagtgcctt 1920
caatactttg cattttggga taataaaaaa ggctccctcc cctgcaaaaa aaaaaaaaaa 1980
aaaa 1984
<210> 15
<211> 1430
<212> RNA
<213> BC030205.1 Homo sapiens tumor necrosis factor, alpha-induced protein 6, mRNA (TNFAIP6)
<400> 15
gtgagcagcc cctaacaggc tgttacttca ctacaactga cgatatgatc atcttaattt 60
acttatttct cttgctatgg gaagacactc aaggatgggg attcaaggat ggaatttttc 120
ataactccat atggcttgaa cgagcagccg gtgtgtacca cagagaagca cggtctggca 180
aatacaagct cacctacgca gaagctaagg cggtgtgtga atttgaaggc ggccatctcg 240
caacttacaa gcagctagag gcagccagaa aaattggatt tcatgtctgt gctgctggat 300
ggatggctaa gggcagagtt ggatacccca ttgtgaagcc agggcccaac tgtggatttg 360
gaaaaactgg cattattgat tatggaatcc gtctcaatag gagtgaaaga tgggatgcct 420
attgctacaa cccacacgca aaggagtgtg gtggcgtctt tacagatcca aagcaaattt 480
ttaaatctcc aggcttccca aatgagtacg aagataacca aatctgctac tggcacatta 540
gactcaagta tggtcagcgt attcacctga gttttttaga ttttgacctt gaagatgacc 600
caggttgctt ggctgattat gttgaaatat atgacagtta cgatgatgtc catggctttg 660
tgggaagata ctgtggagat gagcttccag atgacatcat cagtacagga aatgtcatga 720
ccttgaagtt tctaagtgat gcttcagtga cagctggagg tttccaaatc aaatatgttg 780
caatggatcc tgtatccaaa tccagtcaag gaaaaaatac aagtactact tctactggaa 840
ataaaaactt tttagctgga agatttagcc acttataaaa aaaaaaaaag gatgatcaaa 900
acacacagtg tttatgttgg aatcttttgg aactcctttg atctcactgt tattattaac 960
atttatttat tatttttcta aatgtgaaag caatacataa tttagggaaa attggaaaat 1020
ataggaaact ttaaacgaga aaatgaaacc tctcataatc ccactgcata gaaataacaa 1080
gcgttaacat tttcatattt ttttctttca gtcatttttc tatttgtggt atatgtatat 1140
atgtacctat atgtatttgc atttgaaatt ttggaatcct gctctatgta cagttttgta 1200
ttatactttt taaatcttga actttataaa cattttctga aatcattgat tattctacaa 1260
aaacatgatt ttaaacagct gtaaaatatt ctatgatatg aatgttttat gcattattta 1320
agcctgtctc tattgttgga atttcaggtc attttcataa atattgttgc aataaatatc 1380
cttgaacaca aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 1430
<210> 16
<211> 1650
<212> RNA
<213> BC069716.1 Homo sapiens matrix metallopeptidase 3 (stromelysin 1, progelatinase)
<400> 16
acaaggaggc aggcaagaca gcaaggcata gagacaacat agagctaagt aaagccagtg 60
gaaatgaaga gtcttccaat cctactgttg ctgtgcgtgg cagtttgctc agcctatcca 120
ttggatggag ctgcaagggg tgaggacacc agcatgaacc ttgttcagaa atatctagaa 180
aactactacg acctcgaaaa agatgtgaaa cagtttgtta ggagaaagga cagtggtcct 240
gttgttaaaa aaatccgaga aatgcagaag ttccttggat tggaggtgac ggggaagctg 300
gactccgaca ctctggaggt gatgcgcaag cccaggtgtg gagttcctga cgttggtcac 360
ttcagaacct ttcctggcat cccgaagtgg aggaaaaccc accttacata caggattgtg 420
aattatacac cagatttgcc aaaagatgct gttgattctg ctgttgagaa agctctgaaa 480
gtctgggaag aggtgactcc actcacattc tccaggctgt atgaaggaga ggctgatata 540
atgatctctt ttgcagttag agaacatgga gacttttacc cttttgatgg acctggaaat 600
gttttggccc atgcctatgc ccctgggcca gggattaatg gagatgccca ctttgatgat 660
gatgaacaat ggacaaagga tacaacaggg accaatttat ttctcgttgc tgctcatgaa 720
attggccact ccctgggtct ctttcactca gccaacactg aagctttgat gtacccactc 780
tatcactcac tcacagacct gactcggttc cgcctgtctc aagatgatat aaatggcatt 840
cagtccctct atggacctcc ccctgactcc cctgagaccc ccctggtacc cacggaacct 900
gtccctccag aacctgggac gccagccaac tgtgatcctg ctttgtcctt tgatgctgtc 960
agcactctga ggggagaaat cctgatcttt aaagacaggc acttttggcg caaatccctc 1020
aggaagcttg aacctgaatt gcatttgatc tcttcatttt ggccatctct tccttcaggc 1080
gtggatgccg catatgaagt tactagcaag gacctcgttt tcatttttaa aggaaatcaa 1140
ttctgggcca tcagaggaaa tgaggtacga gctggatacc caagaggcat ccacacccta 1200
ggtttccctc caaccgtgag gaaaatcgat gcagccattt ctgataagga aaagaacaaa 1260
acatatttct ttgtagagga caaatactgg agatttgatg agaagagaaa ttccatggag 1320
ccaggctttc ccaagcaaat agctgaagac tttccaggga ttgactcaaa gattgatgct 1380
gtttttgaag aatttgggtt cttttatttc tttactggat cttcacagtt ggagtttgac 1440
ccaaatgcaa agaaagtgac acacactttg aagagtaaca gctggcttaa ttgttgaaag 1500
agatatgtag aaggcacaat atgggcactt taaatgaagc taataattct tcacctaagt 1560
ctctgtgaat tgaaatgttc gttttctcct gcctgtgctg tgactcgagt cacactcaag 1620
ggaacttgag cgtgaatctg tatcttgccg 1650
<210> 17
<211> 1971
<212> RNA
<213> BC004977.1 Homo sapiens interferon-induced protein with tetratricopeptide repeats 3
<400> 17
caaaatcaac cgggacccca gcttttcaga actgcaggga aacagccatc atgagtgagg 60
tcaccaagaa ttccctggag aaaatccttc cacagctgaa atgccatttc acctggaact 120
tattcaagga agacagtgtc tcaagggatc tagaagatag agtgtgtaac cagattgaat 180
ctttaaacac tgagttcaaa gctacaatgt acaacttgtt ggcctacata aaacacctag 240
atggtaacaa cgaggcagcc ctggaatgct tacggcaagc tgaagagtta atccagcaag 300
aacatgctga ccaagcagaa atcagaagtc tagtcacttg gggaaactac gcctgggtct 360
actatcactt gggcagactc tcagatgctc agatttatgt agataaggtg aaacaaacct 420
gcaagaaatt ttcaaatcca tacagtattg agtattctga acttgactgt gaggaagggt 480
ggacacaact gaagtgtgga agaaatgaaa gggcgaaggt gtgttttgag aaggctctgg 540
aagaaaagcc caacaaccca gaattctcct ctggactggc aattgcgatg taccatctgg 600
ataatcaccc agagaaacag ttctctactg atgttttgaa gcaggccatt gagctgagtc 660
ctgataacca atacgtcaag gttctcttgg gcctgaaact gcagaagatg aataaagaag 720
ctgaaggaga gcagtttgtt gaagaagcct tggaaaagtc tccttgccaa acagatgtcc 780
tccgcagtgc agccaaattt tacagaagaa aaggtgacct agacaaagct attgaactgt 840
ttcaacgggt gttggaatcc acaccaaaca atggctacct ctatcaccag attgggtgct 900
gctacaaggc aaaagtaaga caaatgcaga atacaggaga atctgaagct agtggaaata 960
aagagatgat tgaagcacta aagcaatatg ctatggacta ttcgaataaa gctcttgaga 1020
agggactgaa tcctctgaat gcatactccg atctcgctga gttcctggag acggaatgtt 1080
atcagacacc attcaataag gaagtccctg atgctgaaaa gcaacaatcc catcagcgct 1140
actgcaacct tcagaaatat aatgggaagt ctgaagacac tgctgtgcaa catggtttag 1200
agggtttgtc cataagcaaa aaatcaactg acaaggaaga gatcaaagac caaccacaga 1260
atgtatctga aaatctgctt ccacaaaatg caccaaatta ttggtatctt caaggattaa 1320
ttcataagca gaatggagat ctgctgcaag cagccaaatg ttatgagaag gaactgggcc 1380
gcctgctaag ggatgcccct tcaggcatag gcagtatttt cctgtcagca tctgagcttg 1440
aggatggtag tgaggaaatg ggccagggcg cagtcagctc cagtcccaga gagctcctct 1500
ctaactcaga gcaactgaac tgagacagag gaggaaaaca gagcatcaga agcctgcagt 1560
ggtggttgtg acgggtagga cgataggaag acagggggcc ccaacctggg attgctgagc 1620
agggaagctt tgcatgttgc tctaaggtac atttttaaag agttgttttt tggccgggcg 1680
cagtggctca tgcctgtaat cccagcactt tgggaggccg aggtgggcgg atcacgaggt 1740
ctggagtttg agaccatcct ggctaacaca gtgaaatccc gtctctacta aaaatacaaa 1800
aaattagcca ggcgtggtgg ctggcacctg tagtcccagc tacttgggag gctgaggcag 1860
gagaatggcg tgaacctgga aggaagaggt tgcagtgagc caagattgcg cccctgcact 1920
ccagcctggg caacagagca agactccatc tcaaaaaaaa aaaaaaaaaa a 1971
<210> 18
<211> 1677
<212> RNA
<213> NM_002993.3 Homo sapiens C-X-C motif chemokine ligand 6 (CXCL6), mRNA
<400> 18
accccttctt tccacactgc cccctgagtt cagggaattt ccccagcatc ccaaagcttg 60
agtttcctgc cagtcgggag ggatgaatgc agataaaggg agtgcagaag gcacgaggaa 120
accaaagtgc tctgtatcct ccagtctccg cgcctccacc cagctcagga acccgcgaac 180
cctctcttga ccactatgag cctcccgtcc agccgcgcgg cccgtgtccc gggtccttcg 240
ggctccttgt gcgcgctgct cgcgctgctg ctcctgctga cgccgccggg gcccctcgcc 300
agcgctggtc ctgtctctgc tgtgctgaca gagctgcgtt gcacttgttt acgcgttacg 360
ctgagagtaa accccaaaac gattggtaaa ctgcaggtgt tccccgcagg cccgcagtgc 420
tccaaggtgg aagtggtagc ctccctgaag aacgggaagc aagtttgtct ggacccggaa 480
gccccttttc taaagaaagt catccagaaa attttggaca gtggaaacaa gaaaaactga 540
gtaacaaaaa agaccatgca tcataaaatt gcccagtctt cagcggagca gttttctgga 600
gatccctgga cccagtaaga ataagaagga agggttggtt tttttccatt ttctacatgg 660
attccctact ttgaagagtg tgggggaaag cctacgcttc tccctgaagt ttacagctca 720
gctaatgaag tactaatata gtatttccac tatttactgt tattttacct gataagttat 780
tgaacccttt ggcaattgac catattgtga gcaaagaatc actggttatt agtctttcaa 840
tgaatattga attgaagata actattgtat ttctatcata cattccttaa agtcttaccg 900
aaaaggctgt ggatttcgta tggaaataat gttttattag tgtgctgttg agggaggtat 960
cctgttgttc ttactcactc ttctcataaa ataggaaata ttttagttct gtttcttggg 1020
gaatatgtta ctctttaccc taggatgcta tttaagttgt actgtattag aacactgggt 1080
gtgtcatacc gttatctgtg cagaatatat ttccttattc agaatttcta aaaatttaag 1140
ttctgtaagg gctaatatat tctcttccta tggttttaga cgtttgatgt cttcttagta 1200
tggcataatg tcatgattta ctcattaaac tttgattttg tatgctattt tttcactata 1260
ggatgactat aattctggtc actaaatata cactttagat agatgaagaa gcccaaaaac 1320
agataaattc ctgattgcta atttacatag aaatgtattc tcttggtttt ttaaataaaa 1380
gcaaaattaa caatgatctg tgctctgaaa gttttgaaaa tatatttgaa caatttgaat 1440
ataaattcat catttagtcc tcaaaatata tatagcattg ctaagatttt cagatatcta 1500
ttgtggatct tttaaaggtt ttgaccattt tgttatgagg aattatacat gtatcacatt 1560
cactatatta aaattgcact tttatttttt cctgtgtgtc atgttggttt ttggtacttg 1620
tattgtcatt tggagaaaca ataaaagatt tctaaaccaa aaaaaaaaaa aaaaaaa 1677
<210> 19
<211> 6932
<212> RNA
<213> NM_001165.4 Homo sapiens baculoviral IAP repeat containing 3 (BIRC3)
<400> 19
gcatttaaaa gacagcgtga gactcgcgcc ctccggcacg gaaaaggcca ggcgacaggt 60
gtcgcttgaa aagactgggc ttgtccttgc tggtgcatgc gtcgtcggcc tctgggcagc 120
aggtttacaa aggaggaaaa cgacttcttc tagatttttt tttcagtttc ttctataaat 180
caaaacatct caaaatggag acctaaaatc cttaaaggga cttagtctaa tctcgggagg 240
tagttttgtg catgggtaaa caaattaagt attaactggt gttttactat ccaaagaatg 300
ctaattttat aaacatgatc gagttatata aggtatacca taatgagttt gattttgaat 360
ttgatttgtg gaaataaagg aaaagtgatt ctagctgggg catattgtta aagcattttt 420
ttcagagttg gccaggcagt ctcctactgg cacattctcc cattatgtag aatagaaata 480
gtacctgtgt ttgggaaaga ttttaaaatg agtgacagtt atttggaaca aagagctaat 540
aatcaatcca ctgcaaatta aagaaacatg cagatgaaag ttttgacaca ttaaaatact 600
tctacagtga caaagaaaaa tcaagaacaa agctttttga tatgtgcaac aaatttagag 660
gaagtaaaaa gataaatgtg atgattggtc aagaaattat ccagttattt acaaggccac 720
tgatatttta aacgtccaaa agtttgttta aatgggctgt taccgctgag aatgatgagg 780
atgagaatga tggttgaagg ttacatttta ggaaatgaag aaacttagaa aattaatata 840
aagacagtga tgaatacaaa gaagattttt ataacaatgt gtaaaatttt tggccaggga 900
aaggaatatt gaagttagat acaattactt acctttgagg gaaataattg ttggtaatga 960
gatgtgatgt ttctcctgcc acctggaaac aaagcattga agtctgcagt tgaaaagccc 1020
aacgtctgtg agatccagga aaccatgctt gcaaaccact ggtaaaaaaa aaaaaaaaaa 1080
aaaaaaaaag ccacagtgac ttgcttattg gtcattgcta gtattatcga ctcagaacct 1140
ctttactaat ggctagtaaa tcataattga gaaattctga attttgacaa ggtctctgct 1200
gttgaaatgg taaatttatt attttttttg tcatgataaa ttctggttca aggtatgcta 1260
tccatgaaat aatttctgac caaaactaaa ttgatgcaat ttgattatcc atcttagcct 1320
acagatggca tctggtaact tttgactgtt ttaaaaaata aatccactat cagagtagat 1380
ttgatgttgg cttcagaaac atttagaaaa acaaaagttc aaaaatgttt tcaggaggtg 1440
ataagttgaa taactctaca atgttagttc tttgaggggg acaaaaaatt taaaatcttt 1500
gaaaggtctt attttacagc catatctaaa ttatcttaag aaaattttta acaaagggaa 1560
tgaaatatat atcatgattc tgtttttcca aaagtaacct gaatatagca atgaagttca 1620
gttttgttat tggtagtttg ggcagagtct ctttttgcag cacctgttgt ctaccataat 1680
tacagaggac atttccatgt tctagccaag tatactatta gaataaaaaa acttaacatt 1740
gagttgcttc aacagcatga aactgagtcc aaaagaccaa atgaacaaac acattaatct 1800
ctgattattt attttaaata gaatatttaa ttgtgtaaga tctaatagta tcattatact 1860
taagcaatca tattcctgat gatctatggg aaataactat tatttaatta atattgaaac 1920
caggttttaa gatgtgttag ccagtcctgt tactagtaaa tctctttatt tggagagaaa 1980
ttttagattg ttttgttctc cttattagaa ggattgtaga aagaaaaaaa tgactaattg 2040
gagaaaaatt ggggatatat catatttcac tgaattcaaa atgtcttcag ttgtaaatct 2100
taccattatt ttacgtacct ctaagaaata aaagtgcttc taattaaaat atgatgtcat 2160
taattatgaa atacttcttg ataacagaag ttttaaaata gccatcttag aatcagtgaa 2220
atatggtaat gtattatttt cctcctttga gttaggtctt gtgctttttt ttcctggcca 2280
ctaaatttca caatttccaa aaagcaaaat aaacatattc tgaatatttt tgctgtgaaa 2340
cacttgacag cagagctttc caccatgaaa agaagcttca tgagtcacac attacatctt 2400
tgggttgatt gaatgccact gaaacattct agtagcctgg agaagttgac ctacctgtgg 2460
agatgcctgc cattaaatgg catcctgatg gcttaataca catcactctt ctgtgaaggg 2520
ttttaatttt caacacagct tactctgtag catcatgttt acattgtatg tataaagatt 2580
atacaaaggt gcaattgtgt atttcttcct taaaatgtat cagtatagga tttagaatct 2640
ccatgttgaa actctaaatg catagaaata aaaataataa aaaatttttc attttggctt 2700
ttcagcctag tattaaaact gataaaagca aagccatgca caaaactacc tccctagaga 2760
aaggctagtc ccttttcttc cccattcatt tcattatgaa catagtagaa aacagcatat 2820
tcttatcaaa tttgatgaaa agcgccaaca cgtttgaact gaaatacgac ttgtcatgtg 2880
aactgtaccg aatgtctacg tattccactt ttcctgctgg ggttcctgtc tcagaaagga 2940
gtcttgctcg tgctggtttc tattacactg gtgtgaatga caaggtcaaa tgcttctgtt 3000
gtggcctgat gctggataac tggaaaagag gagacagtcc tactgaaaag cataaaaagt 3060
tgtatcctag ctgcagattc gttcagagtc taaattccgt taacaacttg gaagctacct 3120
ctcagcctac ttttccttct tcagtaacaa attccacaca ctcattactt ccgggtacag 3180
aaaacagtgg atatttccgt ggctcttatt caaactctcc atcaaatcct gtaaactcca 3240
gagcaaatca agatttttct gccttgatga gaagttccta ccactgtgca atgaataacg 3300
aaaatgccag attacttact tttcagacat ggccattgac ttttctgtcg ccaacagatc 3360
tggcaaaagc aggcttttac tacataggac ctggagacag agtggcttgc tttgcctgtg 3420
gtggaaaatt gagcaattgg gaaccgaagg ataatgctat gtcagaacac ctgagacatt 3480
ttcccaaatg cccatttata gaaaatcagc ttcaagacac ttcaagatac acagtttcta 3540
atctgagcat gcagacacat gcagcccgct ttaaaacatt ctttaactgg ccctctagtg 3600
ttctagttaa tcctgagcag cttgcaagtg cgggttttta ttatgtgggt aacagtgatg 3660
atgtcaaatg cttttgctgt gatggtggac tcaggtgttg ggaatctgga gatgatccat 3720
gggttcaaca tgccaagtgg tttccaaggt gtgagtactt gataagaatt aaaggacagg 3780
agttcatccg tcaagttcaa gccagttacc ctcatctact tgaacagctg ctatccacat 3840
cagacagccc aggagatgaa aatgcagagt catcaattat ccattttgaa cctggagaag 3900
accattcaga agatgcaatc atgatgaata ctcctgtgat taatgctgcc gtggaaatgg 3960
gctttagtag aagcctggta aaacagacag ttcagagaaa aatcctagca actggagaga 4020
attatagact agtcaatgat cttgtgttag acttactcaa tgcagaagat gaaataaggg 4080
aagaggagag agaaagagca actgaggaaa aagaatcaaa tgatttatta ttaatccgga 4140
agaatagaat ggcacttttt caacatttga cttgtgtaat tccaatcctg gatagtctac 4200
taactgccgg aattattaat gaacaagaac atgatgttat taaacagaag acacagacgt 4260
ctttacaagc aagagaactg attgatacga ttttagtaaa aggaaatatt gcagccactg 4320
tattcagaaa ctctctgcaa gaagctgaag ctgtgttata tgagcattta tttgtgcaac 4380
aggacataaa atatattccc acagaagatg tttcagatct accagtggaa gaacaattgc 4440
ggagactaca agaagaaaga acatgtaaag tgtgtatgga caaagaagtg tccatagtgt 4500
ttattccttg tggtcatcta gtagtatgca aagattgtgc tccttcttta agaaagtgtc 4560
ctatttgtag gagtacaatc aagggtacag ttcgtacatt tctttcatga agaagaacca 4620
aaacatcgtc taaactttag aattaattta ttaaatgtat tataacttta acttttatcc 4680
taatttggtt tccttaaaat ttttatttat ttacaactca aaaaacattg ttttgtgtaa 4740
catatttata tatgtatcta aaccatatga acatatattt tttagaaact aagagaatga 4800
taggcttttg ttcttatgaa cgaaaaagag gtagcactac aaacacaata ttcaatcaaa 4860
atttcagcat tattgaaatt gtaagtgaag taaaacttaa gatatttgag ttaaccttta 4920
agaattttaa atattttggc attgtactaa taccgggaac atgaagccag gtgtggtggt 4980
atgtgcctgt agtcccaggc tgaggcaaga gaattacttg agcccaggag tttgaatcca 5040
tcctgggcag catactgaga ccctgccttt aaaaacaaac agaacaaaaa caaaacacca 5100
gggacacatt tctctgtctt ttttgatcag tgtcctatac atcgaaggtg tgcatatatg 5160
ttgaatgaca ttttagggac atggtgtttt tataaagaat tctgtgagaa aaaatttaat 5220
aaagcaacaa aaattactct tattcttcat tgctttattt caatgacatt ggatagttta 5280
gtcactccca gactctttcc ataccttctt aaagcctctc aaatattgaa ctacagttta 5340
tactccttcc cataagatgc ttcttcattg acacttgtag aacacggggt caacacatca 5400
taaaatctat tatggaatgc ctgagacaag aatcaaacag tccctttagt aagtttgttt 5460
attcacttct ctattgattc attcaagaag tctcatgcca gccccaccta ttggaagaag 5520
gtctgagttt tattcttatc tctttggtat taattctgaa acttagaaag tacactggtt 5580
agcaatgctt gggaccaaca ggttgttctg gtaaataaat ctgtttcata ttgtcagtgc 5640
aacaaaatgt ccccctctgc attatgttat tggtactcaa cacgtccgag tcataactct 5700
gtcctttgct tcttatagag gtattaggtc ttcaagagca gaagtaagac tgtaataggg 5760
aatactcagg ggaaggcagg caaaggctag tcatctaaac cagttctaga tgtctgtata 5820
ggggcagatg gctctgtaag ggcagaaggg aaagacccct tcataagggt cacagctgac 5880
aatcctataa caaaagacag gttaacaaga gaaaaactta acaaatttat ttaatcacag 5940
atttacatca ccggggagcc ttcgtaatga agatccaaaa ttacagggga aactgtgcat 6000
ttttatgctt aggtttgata atgaatggac agccctgaag aatagtgatt ggaaaaaaag 6060
gatatgatct aatgggaata gacacaggtt ggggacccag caaggcctgt ctgttcagat 6120
tattcttggt ctctgtgcag cattccttcc tcctggatat agggcagggc ctgtatggga 6180
tggggatatt ataacctgct atcaagcaag gtaggtcaga gaatttattt atggccagct 6240
cttacatagt taggtgagga aagattagag tactatcttt aagatgtaag tctggcattg 6300
tggaaagatg gttccagttt ctatgaccta ccttggggaa gaggaattca agtttctgtg 6360
gcttgccttc agggagaatg aggctgagac aggagggcag gataacatca gagaaaaact 6420
ttgcttctga ggccttcact ttgggttttc tgagccccaa catctgctag tgttgtaaag 6480
agaacaatta gggaccaagt gaggggagga aagaatccat ctctgcattc tgatgctggg 6540
agacttattt ccttgaaatg caattgattt tgcctctgct aagaggctct gctggctacc 6600
catgtactag ccagtgtcct gcatgggtgc taggctgaat tatttgtaat tgtgcttagg 6660
tgatttgtaa ctcaggtata gggtatttaa atagtaggca ccctttttgc accatgtgtt 6720
ttttttttta tctagttctt gtatactaca gataatattt gaactttgtc atctcactgt 6780
aaaacttttg ttcatttctc attatggtaa taaatagcta ttataaccaa cccatttatt 6840
caaatatgtt atttccctaa gtgttatttt gacattttgt tttggaaaaa ataaatcacc 6900
atagataata aaaaaaaaaa aaaaaaaaaa aa 6932
<210> 20
<211> 528
<212> RNA
<213> CR541937.1 Homo sapiens BCL2-related protein A1 (BCL2A1)
<400> 20
atgacagact gtgaatttgg atatatttac aggctggctc aggactatct gcagtgcgtc 60
ctacagatac cacaacctgg atcaggtcca agcaaaacgt ccagagtgct acaaaatgtt 120
gcgttctcag tccaaaaaga agtggaaaag aatctgaagt catgcttgga caatgttaat 180
gttgtgtccg tagacactgc cagaacacta ttcaaccaag tgatggaaaa ggagtttgaa 240
gacggcatca ttaactgggg aagaattgta accatatttg catttgaagg tattctcatc 300
aagaaacttc tacgacagca aattgccccg gatgtggata cctataagga gatttcatat 360
tttgttgcgg agttcataat gaataacaca ggagaatgga taaggcaaaa cggaggctgg 420
gaaaatggct ttgtaaagaa gtttgaacct aaatctggct ggatgacttt tctagaagtt 480
acaggaaaga tctgtgaaat gctatctctc ctgaagcaat actgttga 528
<210> 21
<211> 753
<212> RNA
<213> CR536551.1 Homo sapiens GTP cyclohydrolase 1 (GCH1)
<400> 21
atggagaagg gccctgtgcg ggcaccggcg gagaagccgc ggggcgccag gtgcagcaat 60
gggttccccg agcgggatcc gccgcggccc gggcccagca ggccggcgga gaagcccccg 120
cggcccgagg ccaagagcgc gcagcccgcg gacggctgga agggcgagcg gccccgcagc 180
gaggaggata acgagctgaa cctccctaac ctggcagccg cctactcgtc catcctgagc 240
tcgctgggcg agaaccccca gcggcaaggg ctgctcaaga cgccctggag ggcggcctcg 300
gccatgcagt tcttcaccaa gggctaccag gagaccatct cagatgtcct aaacgatgct 360
atatttgatg aagatcatga tgagatggtg attgtgaagg acatagacat gttttccatg 420
tgtgagcatc acttggttcc atttgttgga aaggtccata ttggttatct tcctaacaag 480
caagtccttg gcctcagcaa acttgcgagg attgtagaaa tctatagtag aagactacaa 540
gttcaggagc gccttacaaa acaaattgct gtagcaatca cggaagcctt gcggcctgct 600
ggagtcgggg tagtggttga agcaacacac atgtgtatgg taatgcgagg tgtacagaaa 660
atgaacagca aaactgtgac cagcacaatg ttgggtgtgt tccgggagga tccaaagact 720
cgggaagagt tcctgactct cattaggagc tga 753
<210> 22
<211> 3191
<212> RNA
<213> NM_001200.3 Homo sapiens bone morphogenetic protein 2 (BMP2), mRNA
<400> 22
ccacaaaggg cacttggccc cagggctagg agagcgaggg gagagcacag ccacccgcct 60
cggcggcccg ggactcggct cgactcgccg gagaatgcgc ccgaggacga cggggcgcca 120
gagccgcggt gctttcaact ggcgagcgcg aatgggggtg cactggagta aggcagagtg 180
atgcgggggg gcaactcgcc tggcaccgag atcgccgccg tgcccttccc tggacccggc 240
gtcgcccagg atggctgccc cgagccatgg gccgcggcgg agctagcgcg gagcgcccga 300
ccctcgaccc ccgagtcccg gagccggccc cgcgcggggc cacgcgtccc tcgggcgctg 360
gttcctaagg aggacgacag caccagcttc tcctttctcc cttcccttcc ctgccccgca 420
ctcctccccc tgctcgctgt tgttgtgtgt cagcacttgg ctggggactt cttgaacttg 480
cagggagaat aacttgcgca ccccactttg cgccggtgcc tttgccccag cggagcctgc 540
ttcgccatct ccgagcccca ccgcccctcc actcctcggc cttgcccgac actgagacgc 600
tgttcccagc gtgaaaagag agactgcgcg gccggcaccc gggagaagga ggaggcaaag 660
aaaaggaacg gacattcggt ccttgcgcca ggtcctttga ccagagtttt tccatgtgga 720
cgctctttca atggacgtgt ccccgcgtgc ttcttagacg gactgcggtc tcctaaaggt 780
cgaccatggt ggccgggacc cgctgtcttc tagcgttgct gcttccccag gtcctcctgg 840
gcggcgcggc tggcctcgtt ccggagctgg gccgcaggaa gttcgcggcg gcgtcgtcgg 900
gccgcccctc atcccagccc tctgacgagg tcctgagcga gttcgagttg cggctgctca 960
gcatgttcgg cctgaaacag agacccaccc ccagcaggga cgccgtggtg cccccctaca 1020
tgctagacct gtatcgcagg cactcaggtc agccgggctc acccgcccca gaccaccggt 1080
tggagagggc agccagccga gccaacactg tgcgcagctt ccaccatgaa gaatctttgg 1140
aagaactacc agaaacgagt gggaaaacaa cccggagatt cttctttaat ttaagttcta 1200
tccccacgga ggagtttatc acctcagcag agcttcaggt tttccgagaa cagatgcaag 1260
atgctttagg aaacaatagc agtttccatc accgaattaa tatttatgaa atcataaaac 1320
ctgcaacagc caactcgaaa ttccccgtga ccagactttt ggacaccagg ttggtgaatc 1380
agaatgcaag caggtgggaa agttttgatg tcacccccgc tgtgatgcgg tggactgcac 1440
agggacacgc caaccatgga ttcgtggtgg aagtggccca cttggaggag aaacaaggtg 1500
tctccaagag acatgttagg ataagcaggt ctttgcacca agatgaacac agctggtcac 1560
agataaggcc attgctagta acttttggcc atgatggaaa agggcatcct ctccacaaaa 1620
gagaaaaacg tcaagccaaa cacaaacagc ggaaacgcct taagtccagc tgtaagagac 1680
accctttgta cgtggacttc agtgacgtgg ggtggaatga ctggattgtg gctcccccgg 1740
ggtatcacgc cttttactgc cacggagaat gcccttttcc tctggctgat catctgaact 1800
ccactaatca tgccattgtt cagacgttgg tcaactctgt taactctaag attcctaagg 1860
catgctgtgt cccgacagaa ctcagtgcta tctcgatgct gtaccttgac gagaatgaaa 1920
aggttgtatt aaagaactat caggacatgg ttgtggaggg ttgtgggtgt cgctagtaca 1980
gcaaaattaa atacataaat atatatatat atatatattt tagaaaaaag aaaaaaacaa 2040
acaaacaaaa aaaccccacc ccagttgaca ctttaatatt tcccaatgaa gactttattt 2100
atggaatgga atggaaaaaa aaacagctat tttgaaaata tatttatatc tacgaaaaga 2160
agttgggaaa acaaatattt taatcagaga attattcctt aaagatttaa aatgtattta 2220
gttgtacatt ttatatgggt tcaaccccag cacatgaagt ataatggtca gatttatttt 2280
gtatttattt actattataa ccacttttta ggaaaaaaat agctaatttg tatttatatg 2340
taatcaaaag aagtatcggg tttgtacata attttccaaa aattgtagtt gttttcagtt 2400
gtgtgtattt aagatgaaaa gtctacatgg aaggttactc tggcaaagtg cttagcacgt 2460
ttgctttttt gcagtgctac tgttgagttc acaagttcaa gtccagaaaa aaaaagtgga 2520
taatccactc tgctgacttt caagattatt atattattca attctcagga atgttgcaga 2580
gtgattgtcc aatccatgag aatttacatc cttattaggt ggaatatttg gataagaacc 2640
agacattgct gatctattat agaaactctc ctcctgcccc ttaatttaca gaaagaataa 2700
agcaggatcc atagaaataa ttaggaaaac gatgaacctg caggaaagtg aatgatggtt 2760
tgttgttctt ctttcctaaa ttagtgatcc cttcaaaggg gctgatctgg ccaaagtatt 2820
caataaaacg taagatttct tcattattga tattgtggtc atatatattt aaaattgata 2880
tctcgtggcc ctcatcaagg gttggaaatt tatttgtgtt ttacctttac ctcatctgag 2940
agctctttat tctccaaaga acccagtttt ctaacttttt gcccaacacg cagcaaaatt 3000
atgcacatcg tgttttctgc ccaccctctg ttctctgacc tatcagcttg cttttctttc 3060
caaggttgtg tgtttgaaca catttctcca aatgttaaac ctatttcaga taataaatat 3120
caaatctctg gcatttcatt ctataaagtc caacctgtaa gagaaaaaaa aaaaaaaaaa 3180
aaaaaaaaaa a 3191
<210> 23
<211> 1378
<212> RNA
<213> NM_003956.3 Homo sapiens cholesterol 25-hydroxylase (CH25H), mRNA
<400> 23
agctgccttg cacagcctcg caatgagctg ccacaactgc tccgaccccc aggtcctttg 60
cagctccggg cagctgttcc tgcagcccct ctgggaccac ctgaggagct gggaggccct 120
cctacagtcg cccttcttcc cggtcatctt ctccatcacc acatacgtgg gcttttgcct 180
gcccttcgtg gtcctggata tcctgtgctc ctgggtgccc gccctgcggc gctacaagat 240
ccaccctgac ttctcgccat ccgcgcagca gctgctacct tgcctggggc agaccctcta 300
ccagcatgtg atgtttgtgt tccccgtgac gctgctgcat tgggcccgca gcccggccct 360
cctgccccac gaagctcccg agctgctcct gctgctgcac cacatcctgt tctgcctgct 420
actcttcgac atggagttct tcgtgtggca cctgctgcac cacaaggtgc cctggctgta 480
ccgcaccttc cacaaggtgc accaccagaa ctcgtcctcg ttcgcgctgg caacgcagta 540
tatgagcgtc tgggaactgt tttctttggg cttcttcgac atgatgaacg tcacactgct 600
cgggtgccac ccgctcacca ccctgacctt ccacgtggtc aacatctggc tttccgtgga 660
ggaccactcc ggctacaact tcccttggtc cactcacaga ctggtgccct tcgggtggta 720
cgggggtgtg gtgcaccacg acctgcatca ctctcacttt aactgcaact tcgctccgta 780
ctttacacac tgggacaaaa tactgggaac gctgcggact gcatctgtcc cagcgcggtg 840
atgtggctgc ggtgggtgcc cctaagactc gggactgctg tgcctttcac acttgaatga 900
agagaaacac ctgagctata tattttttta aagcaactaa cttattgctt tatgtttatc 960
tatgaaaacc atagataaaa tctgatgcat ttttgtaatc tgacaaagta atttacatac 1020
tgtttgtgta tcaatacaat tttgtgttct tggtattctt agtctagctc acctcaatag 1080
ccttgaatcc tgcatatgaa ttagacattc atcactggca tatttagaat atctctaaaa 1140
ggacttgttt gtagaataag gaattttcta tgtttcaaag tgttctaaaa cctggctaaa 1200
agaatgtatt tttgtggatg gtgttgactt ctgactctaa aagcaatcaa acatgtttct 1260
gctggacagt gaccaagaat tatagtacct tcttatattt ttttatagaa ctgtatattt 1320
attttgaaag aaatgttatt cgtgctttaa aaaggaaaaa aaaccatgaa tcaaataa 1378
<210> 24
<211> 2621
<212> RNA
<213> BC040592.1 Homo sapiens thymic stromal lymphopoietin (TSLP), mRNA
<400> 24
agagtggact tttttttcaa agaatgctgt ggtgactcga gtacaacaca tgaagaattc 60
cagaaaagag ccatttttga agtcagcggt gaatcagagg ttttctgacc ctctcgagtg 120
ccttctatga agaagagttc aactctggct ccagtttgtc ccctactctt ttcccgaatc 180
cctcgacatt ccttgctctt ttccccaggc accgcatggc ctgtgacatt tgctgggact 240
cacacacggc gtccaacctc ctttctccga gcgatgactc ctaggaactt cccaaggacc 300
agagcgatgc aggctccgac acgcgagggc ggggggcggg ggtgaggggt gcgatggacg 360
ggggagcgga agggaaagag agagagaggg gacctgggtg tagagagggc ccagggccgc 420
atgagccaag ccagggagga gcagggggtt catctcagca acctgatcgg tgtcggcctt 480
tccctccctt caaccctcca ttggtgttgc tggaactggg aagactgcta gacagacatc 540
ctctagggca ctctccctga ctcactttgc tgtgctttta agcgctcttt tctggatcaa 600
caagagtttg ctagtaaaaa tctgagcccg ccatctcgat gcttctcctg tctctaaaac 660
tggtgcccgg gctgaggccc caggtgacag acgttttcca gtctacgctg cgcggggcta 720
agcctctgcg aggcagagcg cactaaagcg tgcgccgcct ccgggagagc tgagctcagg 780
acagcatcgt ctccgtgcgg tcgccgctgg gcacccagca gcgcggtctg gctccgcttc 840
ttgtgtcgct ggccttaaga gtgggactgt gaaggtggct gggcgctgga atttgtggtt 900
ttaaaagttc ttgacacctg ctagaaagtg ctagaggact cttcagcccc taaggtgccc 960
ctagtcacca agagtaggcg ttttttcctg aaattgatat gggaaatttg aaaagtaggg 1020
tttttgagaa caagccacat cagatctttc cccacttatt tcaacctctt atcgttcctg 1080
cccctaaggt tctggtcacg gttgcacatt taatgctttc acatggaagt gctgtcgaag 1140
actgagactg caccccaccc tccaaagcat cccataagca agcacagttt cttactagcc 1200
aaggagaagg gaaagcacta gttgaaagtg gccacaggaa atgctcaaag atgttcagaa 1260
tgcatgggac atatgcaagg actccaaatc cttacagtgg ctgctggttt cagaaggtgt 1320
ttctcccaaa tagaaaggat tggtcacgga aatgccctgt aggagaaaga cactggtatc 1380
catttcttaa aggacattca cacttatgaa gtgtttaggg caaagcaaaa aggaggaagt 1440
ttctttcagg aaaatcttca tcttacaact tgtagggctg gtgttaactt acgacttcac 1500
taactgtgac tttgagaaga ttaaagcagc ctatctcagt actatttcta aagacctgat 1560
tacatatatg agtgggacca aaagtaccga gttcaacaac accgtctctt gtagcaatcg 1620
gccacattgc cttactgaaa tccagagcct aaccttcaat cccaccgccg gctgcgcgtc 1680
gctcgccaaa gaaatgttcg ccatgaaaac taaggctgcc ttagctatct ggtgcccagg 1740
ctattcggaa actcagataa atgctactca ggcaatgaag aagaggagaa aaaggaaagt 1800
cacaaccaat aaatgtctgg aacaagtgtc acaattacaa ggattgtggc gtcgcttcaa 1860
tcgaccttta ctgaaacaac agtaaaccat ctttattatg gtcatatttc acagcaccaa 1920
aataaatcat ctttattaag tagatgaaac attaactcta actgtgacaa agaagaccac 1980
aaatagttat cttttaatta cagaagagtt tcttaactta cttttgtaag tttttattgt 2040
gtaagtttat aatgcagggg aagtactact cctcaaatgt tgagggaagc ttccataaca 2100
ttgatgactg gcttcatggc agtaattctc ggctgtagtt gcataagcat tgctcaagag 2160
gaaaatccaa aagtgcagca ggagaactct tttccctgaa aaaggaaaaa tattgaactc 2220
aatgatagca cctaaactta catttaaaag acagacattc cttctacatg taatgacact 2280
tcttgtgtta aactaaaaat ttacaagaga agaaagtgaa agcaaatggg gtttcacaaa 2340
tagttgtaaa tatagtgaag caatttgaaa taattttcaa gcaaagtatt gtgaaagtat 2400
tctaagccaa gttttaaata ttatctaaca gacaagagtg gtatatacaa gtagatcctg 2460
agaagtacct ttgttacagc tactataaat atacatataa attatagaat ctactttaat 2520
ttattttgtg aacacttttg aaaatgtaca tgttcctttg taattgacac tatatatttc 2580
ttaataaaat aattctcaaa tttgcaaaaa aaaaaaaaaa a 2621
<210> 25
<211> 3505
<212> RNA
<213> NM_001547.4 Homo sapiens IFIT2, mRNA
<400> 25
agtttcactt tcccttttgt aacgtcagct gaagggaaac aaacaaaaag gaaccagagg 60
ccacttgtat atataggtct cttcagcatt tattggtggc agaagaggaa gatttctgaa 120
gagtgcagct gcctgaaccg agccctgccg aacagctgag aattgcactg caaccatgag 180
tgagaacaat aagaattcct tggagagcag cctacggcaa ctaaaatgcc atttcacctg 240
gaacttgatg gagggagaaa actccttgga tgattttgaa gacaaagtat tttaccggac 300
tgagtttcag aatcgtgaat tcaaagccac aatgtgcaac ctactggcct atctaaagca 360
cctcaaaggg caaaacgagg cagccctgga atgcttacgt aaagctgaag agttaatcca 420
gcaagagcat gctgaccagg cagaaatcag aagtctggtc acctggggaa actatgcctg 480
ggtctactat cacatgggcc gactctcaga cgttcagatt tatgtagaca aggtgaaaca 540
tgtctgtgag aagttttcca gtccctatag aattgagagt ccagagcttg actgtgagga 600
agggtggaca cggttaaagt gtggaggaaa ccaaaatgaa agagcgaagg tgtgctttga 660
gaaggctctg gaaaagaagc caaagaaccc agaattcacc tctggactgg caatagcaag 720
ctaccgtctg gacaactggc caccatctca gaacgccatt gaccctctga ggcaagccat 780
tcggctgaat cctgacaacc agtaccttaa agtcctcctg gctctgaagc ttcataagat 840
gcgtgaagaa ggtgaagagg aaggtgaagg agagaagtta gttgaagaag ccttggagaa 900
agccccaggt gtaacagatg ttcttcgcag tgcagccaag ttttatcgaa gaaaagatga 960
gccagacaaa gcgattgaac tgcttaaaaa ggctttagaa tacataccaa acaatgccta 1020
cctgcattgc caaattgggt gctgctatag ggcaaaagtc ttccaagtaa tgaatctaag 1080
agagaatgga atgtatggga aaagaaagtt actggaacta ataggacacg ctgtggctca 1140
tctgaagaaa gctgatgagg ccaatgataa tctcttccgt gtctgttcca ttcttgccag 1200
cctccatgct ctagcagatc agtatgaaga cgcagagtat tacttccaaa aggaattcag 1260
taaagagctt actcctgtag cgaaacaact gctccatctg cggtatggca actttcagct 1320
gtaccaaatg aagtgtgaag acaaggccat ccaccacttt atagagggtg taaaaataaa 1380
ccagaaatca agggagaaag aaaagatgaa agacaaactg caaaaaattg ccaaaatgcg 1440
actttctaaa aatggagcag attctgaggc tttgcatgtc ttggcattcc ttcaggagct 1500
gaatgaaaaa atgcaacaag cagatgaaga ctctgagagg ggtttggagt ctggaagcct 1560
catcccttca gcatcaagct ggaatgggga atgaagaata gagatgtggt gcccactagg 1620
ctactgctga aagggagctg aaattcctcc accaagttgg tattcaaaat atgtaatgac 1680
tggtatggca aaagattgga ctaagacact ggccatacca ctggacaggg ttatgttaac 1740
acctgaattg ctgggtcttg agagagccca aggagttctg ggagagggac cagattgggg 1800
ggtaggtcca cgggcttggt gatagaatta tttctcgatt gacttcttga gtgcaatttg 1860
aactgtaaca tttgcttagt cacctttagt ggagtaatct actgggcttg tttctatatt 1920
tatataaagc agccaaatcc ttcatgtaat attgaagtcc atttttgcaa tgttgttcca 1980
tacttggagt cattttgcat cccatagagg ttagtcctgc atagccagta atgtgctaag 2040
ttcatccaaa agctggcgga ccaaagtcta aatagggctc agtatccccc atcgcttatc 2100
tctgcctcct tcctcctcct tcccagtcta tcatcaacct tgagtattct acacaatgtg 2160
aattcaagtg cctgattaat tgaggtggca acatagtttg agacgagggc agagaacagg 2220
aagatacata gctagaagcg acgggtacaa aaagcaatgt gtacaagaag actttcagca 2280
agtatacaga gagttcacct ctactctgcc ctcctcatag tcataatgta gcaagtaaag 2340
aatgagaatg gattctgtac aatacactag aaaccaacat aatgtatttc tttaaaacct 2400
gtgtgaaaaa ataaatgttc caccagtagg gataggggaa aagtaaccaa aagagagaaa 2460
gagaaaggaa tgctggttta tctttgtaga ttgtaatcga atggagaaat ttgcagtatt 2520
ttagccacta ttaggaattt tttttttttg taaaatgaag actgaactct gttcaaatgc 2580
tttcatgaac ctggtttgag acggtaggaa agcaacaaaa cgtgggaacc tggtgactaa 2640
gggcctggtg caaggacttg ggaaatgtca ttgataatag atggtggggt tttcccccct 2700
ttagaaatgt tggatattaa gtgatataaa cacttctttt aactccgaaa atcttctgag 2760
aaatcacaaa attcacggta tgcttggaac gattgagatt ttctaggtag atgctgaata 2820
gcctagacat caaagttggt gtgaaccaaa atagagtcag ctgacccagc atcagccaca 2880
ctctgggttg gaaaatgttt gcctgttgga attaatttaa gcttaagtat atatcaacat 2940
tattttattg tgcaattaaa acaatacaaa ttcatggttt tttaaagtta aaaattctaa 3000
ccactgtaac aacagttttt gtgttatttt ctgtattaaa catcttgttg cacgcatttg 3060
aggtcatcag ggtgcaaaat ttgtattcct gaaaatgtca tatattttca ttaataaata 3120
acctaaatat gataaaacat aaagcagtgt tctggttcat ctggaatttt gctgtacttt 3180
aaatctttca gactcagcta ctgataaatg aaacgttaca caggtgtgaa ccaaatccaa 3240
ataacctcga ctggtctact atcataatca cctgaacaga acaaaacttt ttcctcagct 3300
ttaagagtcc agggcttcgg ataacagctg ccatctgcca cctgctacca ttgacctacg 3360
tgaacacaga cattctgtct ccaccttgat ggtgggtggg ctgctcccct tttctttgtt 3420
aaattttgtg ctttcatcac attttctcta ttctgacctc tgttatgaga aataaaagtc 3480
actgattcca ttttaaaaaa aaaaa 3505
<210> 26
<211> 7385
<212> RNA
<213> NM_014586.1 Homo sapiens hormonally up-regulated Neu-associated kinase (HUNK), mRNA
<400> 26
ggcgccgccg gaccgcgccc caccccgcgc gcccgagcag ggcgactgtc attagcttcc 60
tggacgggac ccggggcggg atcctggtgt cctgaaaggg gcccgggcga ccctaagagg 120
aagaactttt gggggcgggg tccccggtcc cgcgtcccct gggcagccgc tattgtctac 180
gcgcctcgct gggcggcgcg gggggcgtga tcgcggcggc cccgggctct gggtgcggag 240
acccaggcgg ggctgggccc agggcggcgg cgggagaagc cggggaagcc gaagagcctg 300
gggaggagga gctgcgagcg cgggagacga gcaggagccg cgcgggccgc ggcgagcgcg 360
atgccggcgg cggcggggga cgggctcctg ggggagccgg cggcgcctgg gggcggcggc 420
ggcgcggagg acgcggccag gcccgcggcg gcctgcgagg gaagtttcct gcctgcctgg 480
gtgagcggcg tgccccgcga gcggctccgc gacttccagc accacaagcg cgtgggcaac 540
tacctcatcg gcagcaggaa gctgggcgag ggctcctttg ccaaggtgcg cgaggggctg 600
cacgtgctga ccggggagaa ggtggccata aaagtcattg ataagaagag agccaaaaag 660
gacacctatg tcaccaaaaa cctgcggcga gagggtcaga tccagcagat gatccgccac 720
cccaatatca ctcagctcct tgatatttta gaaacggaaa acagctacta cctggtcatg 780
gagctgtgcc ctgggggcaa cctgatgcac aagatctatg agaagaagcg gctggaggag 840
tccgaagccc gcagatacat ccgacagctc atctctgccg tagagcacct gcaccgggcc 900
ggggtggtcc acagagactt gaagatagag aatttgctac tagatgaaga caataatatc 960
aagctgattg actttggttt gagcaactgc gcagggatcc tgggttactc ggatccgttc 1020
agcacacagt gtggcagccc tgcctacgct gcacctgaac tgctcgccag gaagaaatac 1080
ggccccaaaa tcgatgtctg gtccataggt gtgaacatgt atgccatgtt gaccgggacg 1140
ctgcctttca cggtggagcc tttcagcctg agggctttgt accagaagat ggtagacaaa 1200
gaaatgaacc ccctccccac tcagctctcc acaggtgcca tcagtttcct gcgctctctc 1260
ctggaaccgg atcctgtgaa gaggccaaat attcagcagg cactggcgaa tcgctggctt 1320
aatgagaatt acacgggcaa agtgccctgt aatgtcacct atcccaacag gatttctctg 1380
gaagatctga gcccgagcgt cgtgctgcac atgaccgaga agctgggtta caagaacagc 1440
gacgtgatca acactgtgct ctccaaccgc gcctgccaca tcctggccat ctacttcctc 1500
ttaaacaaga aactggagcg ctatttgtca gggaaatctg acatccagga cagcctctgc 1560
tacaagaccc ggctctacca gatagaaaag tacagggccc ccaaggagtc ctatgaggcc 1620
tctctggaca cctggacacg agatcttgaa ttccatgccg tgcaggataa aaagcccaaa 1680
gaacaagaaa aaagagggga ttttcttcat cgaccattct ccaagaagtt ggacaagaac 1740
ctgccctcgc acaaacagcc ctcaggctcg cttatgacac agattcagaa caccaaagcc 1800
ctcctgaagg accggaaggc ctccaagtcc agcttccccg acaaagattc ctttggctgc 1860
cgcaatattt tccgcaaaac ctcagattcc aattgtgtgg cttcttcttc catggagttc 1920
atccccgtgc caccgcccag gaccccgagg attgtgaaga aaccggagcc ccatcagcca 1980
gggcccggaa gcactggcat cccccacaag gaagaccccc tgatgctgga catggtgcgc 2040
tccttcgagt ctgtggatcg cgacgaccac gtagaagtgc tgtctccctc tcatcactac 2100
aggattctga actccccggt cagcttggct cgcagaaatt ccagcgagag gacgctgtcc 2160
ccgggtctgc catccggaag catgtcgcct ctccatactc ctttgcatcc aactctggtc 2220
tcttttgctc acgaagataa gaacagcccc ccaaaagagg agggcctgtg ttgcccacct 2280
ccggttccca gcaatggccc catgcagcct ctggggagcc ccaattgtgt gaaaagccga 2340
ggccggttcc ctatgatggg catcggacag atgttaagga agcgccatca gagtctgcag 2400
ccatctgcag ataggcccct ggaggccagc ctgcccccac tgcagcccct agcccctgtg 2460
aaccttgcct ttgacatggc cgatggggtc aagacccagt gctaacttgg gccagcgggg 2520
tttggggtat ctctagaaaa cagcaactga acagagctcc acacatctgt cagggtgtga 2580
gcactccaag gcctcgcgtg gagcatcctt agtcccacct gtagctgaat ccacagaccc 2640
aaagcctgca caacccaacc tcgcttaggg acccccagag atgctggaat cgctaggagg 2700
gttggctcca ggggcagcca attcctatca ttcagatctt ccttcctccc aagtactcac 2760
caaccccttc cacttcccac ttcccccagg cttgggggga aaacagggca tgagccttct 2820
ggggcactca gattatggac tgttaccaga tctttcttca cgctgtgcta catgtgtgcc 2880
tctcacagca gttggccaca gttacaggga gagaacaata tcacagtcat tcatccaggc 2940
cacgtttcct ctgcggagtg tagcagccct gcctttcata gcagggatta cctgaaggcc 3000
agcaggagcc gggggcaggc ccaggatcct cagaggaaga tggagaggag cttcggacca 3060
agatcaaacc aaacagtggg gaccccaaca gaagagaaag actgaaggag acactcattt 3120
cccaagcaag attttgatag atttttgttg ttgttgttgt tgaaacatgc taatgattga 3180
attatctttt ccaaagattt tttttaaatg tgatgtcggt aaattgaaat aacataattt 3240
tttaaaactt ggatggagag atgagaagca attccaccaa actcatgttt tcacaggagg 3300
gttcagtgtg gagagcaaaa aagctgactg tggtgatttg ctgagtgctg tggcccacag 3360
gcagggcaag tctcggtggc cctgtgttca tcctgttgtt taaggcatag ccctgatcct 3420
tctggaaggc atagaacacg gttacagctg gttctgtaga aagagggaaa agatgattgt 3480
gacaattcag agcataactc agatggcgag aaggcagcat tatctctgtg cgatgctgat 3540
ttcaagctgc ccacagaact ggtgcggctc agagctcggc gagtttgctg ggagctggga 3600
gcaggcttgc ctggcagaga acctgttcag atacaggcca gtttcttctt cgaggaaagc 3660
caagctcctc aaacagggtt cagtccacgt tgtgttttca cacctttctc caaggatcga 3720
accaaagatg tgtctccagt attgtgtctg tgcccctgtg tgtgttttgt ggacagccgt 3780
gttgtctgac tgtatccagc tggcacttga cagggtgcag tcattggtga gaagaatcag 3840
aaaaagaaga cccatcagca caggttggat aggggttagt gtaggagacc agttacagaa 3900
tggcctggag tcttcaactt ttgaccggtg caggtgtgac cagagaccac ctctgtggcc 3960
acctcagata gtcatctcag tccaaggatc ccaaaacaca aatctagaat tgcaaagcca 4020
gcctttattt ccctggcagg cagccttgcc agaaggcaga gaggcagttc tgaatcattc 4080
tctcattcac cagtggtgac atccttcagt ccctcacatc tctgacagag cgggacagaa 4140
tggatatttg gctgaccttg gtgagacctg gagctgcctg tttcttccct aggggatcac 4200
cacggctcta gggcattcta ggatgaggtc agaccccttg gccattggtg ttattttttg 4260
tatagcttca gactgggttc cagaacttac cattgaaaac agagctttta ggccaggtgt 4320
ggtggctcac acctgtaatc ccagcacttt gggaggccga ggcaggtgga tcgcttgagc 4380
tcaggagttc gagagcagcc tgggcaacat ggtgaaagcc cgtctctacc gaaaaataca 4440
aaaaaaaata gctgggtgtg gtggtacgtg cctgtagtcc cagctacttc ggggactgag 4500
gtgggaggat cacttgaacc taggaggtcg aggctgcagt gagccaagat catgctactg 4560
cactccagct taggtggcaa agtgagaccc tgtctccaaa aaaagaaaat agagctttat 4620
aagcagagag aagaaaataa tcatctaaga ccatctctcc attcgacatg aagtgtacct 4680
tttctaaaga cggtttccag ctgcaacggc tccactttgc aggcttgcag ggtgtatacc 4740
tgcgcattgg gaacttgctg gaacccctga tgcattttcc ttgagagcag gggtacttcc 4800
gccttgccgt tagcttgtgg agaacgtgct tcttattcct ggcaggcttc aagaacagct 4860
gcacatgtgc cgctaactga ccgcgttgcc attggcgacc tggactctga actcaggttt 4920
attctaaacc cagtgagagg tgagggggag tgatgaaagg ggatcagctg tatttgtgtg 4980
tgtgtgtgtg tgtgagcacc tgacaaatct atgaaaccga gtgaaaggag aaatgttaga 5040
ttctttatta ttttattata tttatatgga aagctcgact ctccctttgg taagtccgaa 5100
gcatgttgtc tgttcgaccg tgactgtctt cctcagtctg tgcctgtgat tccagtcacc 5160
ctgtagttac tgacagaaat tgactggact gtcattgtgt gaagtctagg aggaaatgtc 5220
cattttaatt gtatgatttg gtcataagta aggactatat ttatgtcacc attattagat 5280
atatgtactt ttgtaatgac tgtgaaatac acttttccct cactacgact gcttctttat 5340
ttgctgataa atcttaaaac aactaagtac gttgcaaata atagtacagg taccatcttt 5400
tatgtgaagt tctttttctt tttttgagac agggtcttgc tctgtcaccc aggctggagt 5460
gcagtggcac aatcacagtt cactgcagcc tcaacctctc cagattcaag tgatcctccc 5520
atctcagcct cccaagtagc tgggactaca gttgtgcacc acaatgccta gctaattttt 5580
tttgtatttt gtagaaatgg ggtttcgcca tgttgctcag gctgatctca aactcctggg 5640
ctccaacgat ctgcccacct tggcctccca aagtgctgag attacaggcg tgagccactg 5700
tgcctggcct tatgtaaagc tcttgaccta gcatctgact ggaaacaagc gggaattgca 5760
ttggggggca ttttctgggc cagtttccct gccttatttt acctgcaata ggtgtgccta 5820
caaaagtctt tctgacatac acactgcagg tggcagttca agaagaatca acctttttca 5880
tttggggata ttaggatctt ccttggagac tctgaaaatg gcacacaaag aatggcagtt 5940
atgaacgtga cttctagatt ttgtccttgt aggaggcctt ggtcatggat aggggaagag 6000
ggatgatggg atggaatggg agggtgggat ctagatgacc tcttgaaatt gtcccagtta 6060
ctgcttcctt cataactgtt cacaaaacgt ttttcatata taccaccttg tttcccctgg 6120
gaagtgaggg gacgaagcct tagagggtga catagctaga aagtggagaa gctcactgtt 6180
cactgtgcaa agccccagta gtcggattcc ggggaaaaga acaagtatct agttttgatg 6240
acaatgtttt cttgtaagaa tcccaacact ttagaataga aaaggaccta agattctctg 6300
gctcagcccc agcctttctg aagaagggaa aactagggac ccagatggtt taaggacacc 6360
ccagagtccc cagatgagct ggcatttgag ctggtctgga gcagagtttc tccctcaaag 6420
aacacagaga aatcagagag tggctgccat ggtcagaggg ggatgtcaac aacagatcaa 6480
gccgtcatca caacaggtat ttctgaagtt cctgcaggga ctaggtcttg catttttaag 6540
tccttttcaa aactgtgcag cttcctgaac cttatgctgt ttgtcccatc cactcttgaa 6600
gctggggaaa gacagctttc tttgggaact ctgtctttct cagttgactt cccaagtaag 6660
cagcaaaccc ctggatagcc ttgttatcta ctttaggtat taagaggcta ttgggtttta 6720
ctagattaaa tcaataaaac atttcctata gagccatatc atacactgaa gcaaattcag 6780
aaagaatgca aaactgctat cttttggggg agtctggaag cctgttggtt agtgtattta 6840
ttttctttgt ggggtcttct gtgagctaca ggcacagtaa gaataattca gagcggtact 6900
gggagttggt tcaatttcat gtcatcactt ttcaatgaag ggagtgcatt tcctgagtag 6960
taaatgagta tattatttgt ggcagctttt ctgttaaggg agctttccag acatctggtt 7020
gcaaagacaa ataggatata tatttgtact tcttctctgt ggacatgttt ttgtgacaca 7080
cagttatctc taggagttga cgtctgtggg cactaaggga ctgaggttgg gggagaaagc 7140
tgaggaggct ttggaagaga aggtgaggag catttcagga tttgcagtcc ccctccacat 7200
gtatccacat ctgagctggt ggtgttccaa taatgaggca tttggggcaa ccaattttgg 7260
aaggatagaa tagctttatg tggagcaaac ttgaggatca attggagttg agtggtttaa 7320
aacttaaaga tggcacagga agctgtatca tttacaggtg aaaaaaataa atgggtctga 7380
cttca 7385
<210> 27
<211> 1393
<212> RNA
<213> NM_015675.3 Homo sapiens growth arrest and DNA damage inducible beta (GADD45B), mRNA
<400> 27
tcagatcgcc gaagcgtcgg actaccgttg gtttccgcaa cttcctggat tatcctcgcc 60
aaggactttg caatatattt ttccgccttt tctggaagga tttcgctgct tcccgaaggt 120
cttggacgag cgctctagct ctgtgggaag gttttgggct ctctggctcg gattttgcaa 180
tttctccctg gggactgccg tggagccgca tccactgtgg attataattg caacatgacg 240
ctggaagagc tcgtggcgtg cgacaacgcg gcgcagaaga tgcagacggt gaccgccgcg 300
gtggaggagc ttttggtggc cgctcagcgc caggatcgcc tcacagtggg ggtgtacgag 360
tcggccaagt tgatgaatgt ggacccagac agcgtggtcc tctgcctctt ggccattgac 420
gaggaggagg aggatgacat cgccctgcaa atccacttca cgctcatcca gtccttctgc 480
tgtgacaacg acatcaacat cgtgcgggtg tcgggcatgc agcgcctggc gcagctcctg 540
ggagagccgg ccgagaccca gggcaccacc gaggcccgag acctgcattg tctcctggtc 600
acgaaccctc acacggacgc ctggaagagc cacggcttgg tggaggtggc cagctactgc 660
gaagaaagcc ggggcaacaa ccagtgggtc ccctacatct ctcttcagga acgctgaggc 720
ccttcccagc agcagaatct gttgagttgc tgccacaaac aaaaaataca ataaatattt 780
gaaccccctc ccccccagca caaccccccc aaaacaaccc aacccacgag gaccatcggg 840
ggcagagtcg ttggagactg aagaggaaga ggaggaggag aaggggagtg agcggccgcc 900
cccagggcgg agatccagga gctggcggcc gccgatccga tggagaaggg gggacccagg 960
ccagcaggag acaggacccc cgaagctgag gccttgggat ggagcagaag ccggagtggc 1020
ggggcacgct gccgccttcc ccatcacgga gggtccagac tgtccactcg ggggtggagt 1080
gagactgact gcaagcccca ccctccttga gactggagct ggcgtctgca tacgagagac 1140
ttggttgaac ttggttggtc cttgtctgca ccctcgacaa gaccacactt tgggacttgg 1200
gagctggggc tgaagttgct ctgtacccat gaactcccag tttgcgaatt atagagacaa 1260
tctattttgt tacttgcact tgttattcga accactgaga gcgagatggg aagcatagat 1320
atctatattt ttatttctac tatgagggcc ttgtaataaa tttctaaagc ctctgaaaaa 1380
aaaaaaaaaa aaa 1393
<210> 28
<211> 2950
<212> RNA
<213> BC095399.1 Homo sapiens Kruppel-like factor 10 (KLF10), mRNA
<400> 28
agacggcgct gagcgcggcg gcggcgggag cggcgtcgag tgtctccgtg cgcccgtctg 60
tggccaagca gccagcagcc tagcagccag tcagcttgcc gccggcggcc aagcagccaa 120
ccatgctcaa cttcggtgcc tctctccagc agactgcgga ggaaagaatg gaaatgattt 180
ctgaaaggcc aaaagagagt atgtattcct ggaacaaaac tgcagagaaa agtgattttg 240
aagctgtaga agcacttatg tcaatgagct gcagttggaa gtctgatttt aagaaatacg 300
ttgaaaacag acctgttaca ccagtatctg atttgtcaga ggaagagaat ctgcttccgg 360
gaacacctga ttttcataca atcccagcat tttgtttgac tccaccttac agtccttctg 420
actttgaacc ctctcaagtg tcaaatctga tggcaccagc gccatctact gtacacttca 480
agtcactctc agatactgcc aaacctcaca ttgccgcacc tttcaaagag gaagaaaaga 540
gcccagtatc tgcccccaaa ctccccaaag ctcaggcaac aagtgtgatt cgtcatacag 600
ctgatgccca gctatgtaac caccagacct gcccaatgaa agcagccagc atcctcaact 660
atcagaacaa ttcttttaga agaagaaccc acctaaatgt tgaggctgca agaaagaaca 720
taccatgtgc cgctgtgtca ccaaacagat ccaaatgtga gagaaacaca gtggcagatg 780
ttgatgagaa agcaagtgct gcactttatg acttttctgt gccttcctca gagacggtca 840
tctgcaggtc tcagccagcc cctgtgtccc cacaacagaa gtcagtgttg gtctctccac 900
ctgcagtatc tgcaggggga gtgccaccta tgccggtcat ctgccagatg gttccccttc 960
ctgccaacaa ccctgttgtg acaacagtcg ttcccagcac tcctcccagc cagccaccag 1020
ccgtttgccc ccctgttgtg ttcatgggca cacaagtccc caaaggcgct gtcatgtttg 1080
tggtacccca gcccgttgtg cagagttcaa agcctccggt ggtgagcccg aatggcacca 1140
gactctctcc cattgcccct gctcctgggt tttccccttc agcagcaaaa gtcactcctc 1200
agattgattc atcaaggata aggagtcaca tctgtagcca cccaggatgt ggcaagacat 1260
actttaaaag ttcccatctg aaggcccaca cgaggacgca cacaggagaa aagcctttca 1320
gctgtagctg gaaaggttgt gaaaggaggt ttgcccgttc tgatgaactg tccagacaca 1380
ggcgaaccca cacgggtgag aagaaatttg cgtgccccat gtgtgaccgg cggttcatga 1440
ggagtgacca tttgaccaag catgcccggc gccatctatc agccaagaag ctaccaaact 1500
ggcagatgga agtgagcaag ctaaatgaca ttgctctacc tccaacccct gctcccacac 1560
agtgacagac cggaaagtga agagtcagaa ctaactttgg tctcagcggg agccagtggt 1620
gatgtaaaaa tgcttccact gcaagtctgt ggccccacaa cgtgggctta aagcagaagc 1680
cccacagcct ggcacgaagg ccccgcctgg gttaggtgac taaaagggct tcggccacag 1740
gcaggtcaca gaaaggcagg tttcatttct tatcacataa gagagatgag aaagctttta 1800
ttcctttgaa tattttttga aggtttcaga tgaggtcaac acaggtagca cagattttga 1860
atctgtgtgc atatttgtta ctttactttt gctgtttata cttgagacca acttttcaat 1920
gtgattcttc taaagcactg gtttcaagaa tatggaggct ggaaggaaat aaacattacg 1980
gtacagacat ggagatgtaa aatgagtttg tattattaca aatattgtca tctttttcta 2040
gagttatctt ctttattatt cctagtcttt ccagtcaaca tcgtggatgt agtgattaaa 2100
tatatctaga actatcattt ttacactatt gtgaatattt ggaattgaac gactgtatat 2160
tgctaagagg gcccaaagaa ttggaatcct ccttaattta attgctttga aacatagcta 2220
caatttgttt ttgcattttt gttttgaaag tttaacaaat gactgtatct aggcatttca 2280
ttatgctttg aactttagtt tgcctgcagt ttcttgtgta gatttgaaaa ttgtatacca 2340
atgtgttttc tgtagactct aagatacact gcactttgtt tagaaaaaaa actgaagatg 2400
aaatatatat tgtaaagaag ggatattaag aatcttagat aacttcttga aaaagatggc 2460
ttatgtcatc agtaaagtac ctttatgtta tgaggatata atgtgtgctt tattgaatta 2520
gaaaattagt gaccattatt cacaggtgga caaatgttga tgttgtcctg ttaatttata 2580
ggcgtttttt ggggatgtgg aggtagttgg gtagaaaaat tattagaaca ttcacttttg 2640
ttaacagtat ttctctttta ttctgttata tagtggatga tatacacagt ggcaaaacaa 2700
aagtacattg cttaaaatat atagtgaaaa atgtcactat atcttcccat ttaacattgt 2760
ttttgtatat tgggtgtaga tttctgacat caaaacttgg acccttggaa aacaaaagtt 2820
ttaattaaaa aaaatccttg tgacttacaa tttgcacaat atttcttttg ttgtacttta 2880
tatcttgttt acaataaaga attccctttg gtaaaaaaaa aaaaaaaaaa aaacaaaaaa 2940
aaaaaaaaaa 2950
<210> 29
<211> 926
<212> RNA
<213> X77956.1 Homo sapiens Id1, mRNA
<400> 29
ggggcccatt ctgtttcagc cagtcgccaa gaatcatgaa agtcgccagt ggcagcaccg 60
ccaccgccgc cgcgggcccc agctgcgcgc tgaaggccgg caagacagcg agcggtgcgg 120
gcgaggtggt gcgctgtctg tctgagcaga gcgtggccat ctcgcgctgc cggggcgccg 180
gggcgcgcct gcctgccctg ctggacgagc agcaggtaaa cgtgctgctc tacgacatga 240
acggctgtta ctcacgcctc aaggagctgg tgcccaccct gccccagaac cgcaaggtga 300
gcaaggtgga gattctccag cacgtcatcg actacatcag ggaccttcag ttggagctga 360
actcggaatc cgaagttggg acccccgggg gccgagggct gccggtccgg gctccgctca 420
gcaccctcaa cggcgagatc agcgccctga cggccgaggc ggcatgcgtt cctgcggacg 480
atcgcatctt gtgtcgctga agcgcctccc ccagggaccg gcggacccca gccatccagg 540
gggcaagagg aattacgtgc tctgtgggtc tcccccaacg cgcctcgccg gatctgaggg 600
agaacaagac cgatcggcgg ccactgcgcc cttaactgca tccagcctgg ggctgaggct 660
gaggcactgg cgaggagagg gcgctcctct ctgcacacct actagtcacc agagacttta 720
gggggtggga ttccactcgt gtgtttctat tttttgaaaa gcagacattt taaaaaatgg 780
tcacgtttgg tgcttctcag atttctgagg aaattgcttt gtattgtata ttacaatgat 840
caccgactga gaatattgtt ttacaatagt tctgtggggc tgtttttttg ttattaaaca 900
aataatttag atggtgaaaa aaaaaa 926
<210> 30
<211> 1675
<212> RNA
<213> BC034145.1 Homo sapiens transmembrane 4 L six family member 1 (TM4SF1), mRNA
<400> 30
agagcctgcc attaggacca atgaaagcaa agtacctcat cccctcagtg actaagaatt 60
gcagtattta agaggtagca ggaatgggct gagagtggtg tttgctttct ccaccagaag 120
ggcacacttt catctaattt ggggtatcac tgagctgaag acaaagagaa gggggagaaa 180
acctagcaga ccaccatgtg ctatgggaag tgtgcacgat gcatcggaca ttctctggtg 240
gggctcgccc tcctgtgcat cgcggctaat attttgcttt actttcccaa tggggaaaca 300
aagtatgcct ccgaaaacca cctcagccgc ttcgtgtggt tcttttctgg catcgtagga 360
ggtggcctgc tgatgctcct gccagcattt gtcttcattg ggctggaaca ggatgactgc 420
tgtggctgct gtggccatga aaactgtggc aaacgatgtg cgatgctttc ttctgtattg 480
gctgctctca ttggaattgc aggatctggc tactgtgtca ttgtggcagc ccttggctta 540
gcagaaggac cactatgtct tgattccctc ggccagtgga actacacctt tgccagcacc 600
gagggccagt accttctgga tacctccaca tggtccgagt gcactgaacc caagcacatt 660
gtggaatgga atgtatctct gttttctatc ctcttggctc ttggtggaat tgaattcatc 720
ttgtgtctta ttcaagtaat aaatggagtg cttggaggca tatgtggctt ttgctgctct 780
caccaacagc aaatgactgc taaaagaacc aacccaggac agagccacaa tcttcctcta 840
tttcattgta atttatatat ttcacttgta ttcatttgta aaactttgta ttagtgtaac 900
atactcccca cagtctactt ttacaaacgc ctgtaaagac tggcatcttc acaggatgtc 960
agtgtttaaa tttagtaaac ttcttttttg tttgtttatt tgtttttgtt tttttttaag 1020
gaatgaggaa acaaaccacc ctctgggggt agtttacaga ctgagtgaca gtactcagta 1080
tatctgagat aaactctata atgttttgga taaaaatagc attccaatca ctattgtata 1140
tatgtgcatg tattttttaa attaaagatg tctagttgct ttttataaga ccaagaagga 1200
gaaaatccga caacctggaa agatttttgt tttcactgct tgtatgatgt ttcccattca 1260
tacacctata aatctctaac aagaggccct ttgaactgcc ttgtgttctg tgagaaacaa 1320
atatttactt agagtggaag gactgattga gaatgttcca atccaaatga atgcatcaca 1380
acttacaatg ctgctcattg ttgtgagtac tatgagattc aaatttttct aacatatgga 1440
aagccttttg tcctccaaag atgagtacta gggatcatgt gtttaaaaaa agaaaggcta 1500
cgatgactgg gcaagaagaa agatgggaaa ctgaataaag cagttgatca gcatcattgg 1560
aacatgggga cgagtgacgg caggaggacc acgaggaaat accctcaaaa ctaacttgtt 1620
tacaacaaaa tagagtattc actaccaaaa aaaaaaaaaa aaaaaaaaaa aaaaa 1675
<210> 31
<211> 3319
<212> RNA
<213> NM_001320559.1 Homo sapiens cysteine and serine rich nuclear protein 1 (CSRNP1)
<400> 31
ggaatggagg ccaacgtcaa agccagcctg ttccccagag tgcctggcta gcctggagca 60
agggcccgca gccctgcctg tgtgcagagt ggcgtgcctg tttggatgtg ctggaggagg 120
aggaggagga agcagagcca ccataccagg gccgtgcggg ctgtgcgggc tgtagggcgt 180
acacacacac acatacacac acacacacac acacacacag gcacacagat gcaagctgtg 240
tgaatcaccc agcctgtgag tcagcgccag gattcctgtc ggggaatgag tgagaccagg 300
ctgaggctgt ctgtccccag accccagagc acgtccggca ccaccatgac tgggctgttg 360
aagaggaaat ttgaccagct ggatgaggac aactcctcgg tctcctcctc ctcctcttcc 420
tctgggtgcc agtctcgctc ctgctcccca agctcttctg tctcccgtgc ctgggactca 480
gaggaggaag gcccctggga tcagatgccc ctgcctgacc gtgacttctg cggccccaga 540
agtttcaccc ccctgtctat cctgaagcgg gctcgccggg agcgcccagg ccgtgtagcc 600
tttgatggga tcaccgtctt ctacttcccc cgctgccagg gcttcaccag tgtgcccagc 660
cgtggtggct gtactctggg tatggccctt cgccacagtg cttgccgtcg cttctctttg 720
gctgagtttg cgcaggagca agcccgtgca cggcacgaga agctccgcca gcgcttgaaa 780
gaggagaagt tggagatgct gcagtggaag ctttcggcag ctggggtacc ccaggcagag 840
gcagggctgc cacctgtggt ggatgccatt gatgacgcct ctgtggagga ggacttggca 900
gtcgctgtgg caggtggccg gttggaagaa gtgagcttcc tacagcccta cccagcccgg 960
cgacgtcgag ctctgctgag ggcttcaggt gtgcgaagga tcgatcggga ggagaagcgg 1020
gagctgcagg cactgcgcca atcccgggag gattgtggct gtcactgcga taggatctgc 1080
gaccctgaga cctgcagctg cagcctggca ggcatcaagt gccagatgga ccacacagca 1140
ttcccctgtg gctgctgcag ggagggctgt gagaacccca tgggccgtgt ggaatttaat 1200
caggcaagag ttcagaccca tttcatccac acactcaccc gcctgcagtt ggaacaggag 1260
gctgagagct ttagggagct ggaggcccct gcccagggca gcccacccag ccctggtgag 1320
gaggccctgg tccctacttt cccactggcc aagcccccca tgaacaatga gctgggagac 1380
aacagctgca gcagcgacat gactgattct tctacagcat cttcatcagc atcgggcact 1440
agtgaggctc ctgactgccc cacccaccca ggcctgcctg gccctggctt ccagcctggc 1500
gttgatgatg acagcctggc acgcatcttg agtttcagtg actctgactt cggtggggag 1560
gaggaggaag aggaggaagg gagcgtgggg aacctggaca acctcagctg cttccatcca 1620
gctgacatct ttggtactag tgaccctggt ggcctggcca gctggaccca cagctattct 1680
ggctgtagct tcacatcagg cgtcctggat gagaatgcca acctggatgc cagctgcttc 1740
ctaaatggtg gccttgaagg gtcaagggaa ggcagccttc ctggcacctc agtgccaccc 1800
agcatggacg ctggccggag tagctcagtg gatctcagct tgtcttcttg tgactccttt 1860
gagttactcc aggctctgcc agattatagt ctggggcctc actacacatc acagaaggtg 1920
tctgacagcc tggacaacat cgaggcacct cacttccccc tgcctggcct gtctccacct 1980
ggggatgcca gcagttgctt cctggagtcc ctcatgggct tctccgagcc agccgccgaa 2040
gccctagatc cctttattga cagccagttt gaggacactg tcccagcatc tctaatggag 2100
cctgtgccgg tgtgaggacc aggatgtctt ttcccagccc caagagacct gttgctgctt 2160
tcttgtaatt atggggctcc ccagagtctg cgtaacagtc tcccactggc tggctcaccc 2220
acaggtgcca tgtgcacact cctggttttc aaacaattct ctggatttat ttatttgttt 2280
taacttttct gtgctgaaga gaggactggg gggagggggc ttcccctttc agctgcccgg 2340
ccccccacac ccacagcttg ctcttctatc tccacaacgt gagcctggaa gaggagaaaa 2400
tgtggctcct ctggagcttg gcagaccact tttcggtctt tgcgtgatgt tccttagccc 2460
aaagacggtg agacagggct gaaatcaggt ggcttctgcc accctgagcc ctagacccat 2520
gggtggctaa atccactgga ctgtgaagac tataatttat ttccataatt tatttggaga 2580
ttgaggaggc tttggttgca cttctttggc tggtgggtaa tgccaggggt ggggtgggca 2640
caggccctca agagcccctt ttgccttgta gtcctacacc ttgccctgcc tgggctttgg 2700
tgcagactag gtgtggattt gagctctgtg atctatgtct gctgcctggc tcctagatgg 2760
ctctgtgggc aggtgctggc caaggacatc atctaggcag ggggagagcc tgggctgaac 2820
agctgtgacc aaaactccct tctgccccac cctgccccct ccacttcctg ccctctgttc 2880
catcttcccc cttcccaaag gccacagcct ttattccagg cccagggatg taggaggggg 2940
aaggaggaaa caggaagccc agagagggca aagggcctac ctcggggcgc gaaccatgcc 3000
ccagactatt atctcagggc tttctgggca ctgcacttca gcgtggccca cctgcccatg 3060
ccctgaggcc agttggcgag gggtggctcc tgagggtttt tatacccttt gtttgctaat 3120
gtttaatttt gcatcataat ttctacattg tccctgagtg tcagaactat aatttattcc 3180
atttctctct gtgtctgtgc caagaaacgc aggctctggg cctgcccctt gcccaggagg 3240
ccttgccagc ctgtgtgctt gtgggaacac cttgtacctg agcttacagg taccaataaa 3300
gaggctttat ttttagcaa 3319
<210> 32
<211> 381
<212> PRT
<213> NP_002843.2 pentraxin-related protein (PTX3) [Homo sapiens]
<400> 32
Met His Leu Leu Ala Ile Leu Phe Cys Ala Leu Trp Ser Ala Val Leu
1 5 10 15
Ala Glu Asn Ser Asp Asp Tyr Asp Leu Met Tyr Val Asn Leu Asp Asn
20 25 30
Glu Ile Asp Asn Gly Leu His Pro Thr Glu Asp Pro Thr Pro Cys Ala
35 40 45
Cys Gly Gln Glu His Ser Glu Trp Asp Lys Leu Phe Ile Met Leu Glu
50 55 60
Asn Ser Gln Met Arg Glu Arg Met Leu Leu Gln Ala Thr Asp Asp Val
65 70 75 80
Leu Arg Gly Glu Leu Gln Arg Leu Arg Glu Glu Leu Gly Arg Leu Ala
85 90 95
Glu Ser Leu Ala Arg Pro Cys Ala Pro Gly Ala Pro Ala Glu Ala Arg
100 105 110
Leu Thr Ser Ala Leu Asp Glu Leu Leu Gln Ala Thr Arg Asp Ala Gly
115 120 125
Arg Arg Leu Ala Arg Met Glu Gly Ala Glu Ala Gln Arg Pro Glu Glu
130 135 140
Ala Gly Arg Ala Leu Ala Ala Val Leu Glu Glu Leu Arg Gln Thr Arg
145 150 155 160
Ala Asp Leu His Ala Val Gln Gly Trp Ala Ala Arg Ser Trp Leu Pro
165 170 175
Ala Gly Cys Glu Thr Ala Ile Leu Phe Pro Met Arg Ser Lys Lys Ile
180 185 190
Phe Gly Ser Val His Pro Val Arg Pro Met Arg Leu Glu Ser Phe Ser
195 200 205
Ala Cys Ile Trp Val Lys Ala Thr Asp Val Leu Asn Lys Thr Ile Leu
210 215 220
Phe Ser Tyr Gly Thr Lys Arg Asn Pro Tyr Glu Ile Gln Leu Tyr Leu
225 230 235 240
Ser Tyr Gln Ser Ile Val Phe Val Val Gly Gly Glu Glu Asn Lys Leu
245 250 255
Val Ala Glu Ala Met Val Ser Leu Gly Arg Trp Thr His Leu Cys Gly
260 265 270
Thr Trp Asn Ser Glu Glu Gly Leu Thr Ser Leu Trp Val Asn Gly Glu
275 280 285
Leu Ala Ala Thr Thr Val Glu Met Ala Thr Gly His Ile Val Pro Glu
290 295 300
Gly Gly Ile Leu Gln Ile Gly Gln Glu Lys Asn Gly Cys Cys Val Gly
305 310 315 320
Gly Gly Phe Asp Glu Thr Leu Ala Phe Ser Gly Arg Leu Thr Gly Phe
325 330 335
Asn Ile Trp Asp Ser Val Leu Ser Asn Glu Glu Ile Arg Glu Thr Gly
340 345 350
Gly Ala Glu Ser Cys His Ile Arg Gly Asn Ile Val Gly Trp Gly Val
355 360 365
Thr Glu Ile Gln Pro His Gly Gly Ala Gln Tyr Val Ser
370 375 380
<210> 33
<211> 107
<212> PRT
<213> NP_001502.1 growth-regulated alpha protein (CXCL1) [Homo sapiens]
<400> 33
Met Ala Arg Ala Ala Leu Ser Ala Ala Pro Ser Asn Pro Arg Leu Leu
1 5 10 15
Arg Val Ala Leu Leu Leu Leu Leu Leu Val Ala Ala Gly Arg Arg Ala
20 25 30
Ala Gly Ala Ser Val Ala Thr Glu Leu Arg Cys Gln Cys Leu Gln Thr
35 40 45
Leu Gln Gly Ile His Pro Lys Asn Ile Gln Ser Val Asn Val Lys Ser
50 55 60
Pro Gly Pro His Cys Ala Gln Thr Glu Val Ile Ala Thr Leu Lys Asn
65 70 75 80
Gly Arg Lys Ala Cys Leu Asn Pro Ala Ser Pro Ile Val Lys Lys Ile
85 90 95
Ile Glu Lys Met Leu Asn Ser Asp Lys Ser Asn
100 105
<210> 34
<211> 107
<212> PRT
<213> NP_002080.1 C-X-C motif chemokine 2 (CXCL2) [Homo sapiens]
<400> 34
Met Ala Arg Ala Thr Leu Ser Ala Ala Pro Ser Asn Pro Arg Leu Leu
1 5 10 15
Arg Val Ala Leu Leu Leu Leu Leu Leu Val Ala Ala Ser Arg Arg Ala
20 25 30
Ala Gly Ala Pro Leu Ala Thr Glu Leu Arg Cys Gln Cys Leu Gln Thr
35 40 45
Leu Gln Gly Ile His Leu Lys Asn Ile Gln Ser Val Lys Val Lys Ser
50 55 60
Pro Gly Pro His Cys Ala Gln Thr Glu Val Ile Ala Thr Leu Lys Asn
65 70 75 80
Gly Gln Lys Ala Cys Leu Asn Pro Ala Ser Pro Met Val Lys Lys Ile
85 90 95
Ile Glu Lys Met Leu Lys Asn Gly Lys Ser Asn
100 105
<210> 35
<211> 654
<212> PRT
<213> NP_006282.2 tumor necrosis factor alpha-induced protein 2 (TNFAIP2) [Homo sapiens]
<400> 35
Met Ser Glu Ala Ser Ser Glu Asp Leu Val Pro Pro Leu Glu Ala Gly
1 5 10 15
Ala Ala Pro Tyr Arg Glu Glu Glu Glu Ala Ala Lys Lys Lys Lys Glu
20 25 30
Lys Lys Lys Lys Ser Lys Gly Leu Ala Asn Val Phe Cys Val Phe Thr
35 40 45
Lys Gly Lys Lys Lys Lys Gly Gln Pro Ser Ser Ala Glu Pro Glu Asp
50 55 60
Ala Ala Gly Ser Arg Gln Gly Leu Asp Gly Pro Pro Pro Thr Val Glu
65 70 75 80
Glu Leu Lys Ala Ala Leu Glu Arg Gly Gln Leu Glu Ala Ala Arg Pro
85 90 95
Leu Leu Ala Leu Glu Arg Glu Leu Ala Ala Ala Ala Ala Ala Gly Gly
100 105 110
Val Ser Glu Glu Glu Leu Val Arg Arg Gln Ser Lys Val Glu Ala Leu
115 120 125
Tyr Glu Leu Leu Arg Asp Gln Val Leu Gly Val Leu Arg Arg Pro Leu
130 135 140
Glu Ala Pro Pro Glu Arg Leu Arg Gln Ala Leu Ala Val Val Ala Glu
145 150 155 160
Gln Glu Arg Glu Asp Arg Gln Ala Ala Ala Ala Gly Pro Gly Thr Ser
165 170 175
Gly Leu Ala Ala Thr Arg Pro Arg Arg Trp Leu Gln Leu Trp Arg Arg
180 185 190
Gly Val Ala Glu Ala Ala Glu Glu Arg Met Gly Gln Arg Pro Ala Ala
195 200 205
Gly Ala Glu Val Pro Glu Ser Val Phe Leu His Leu Gly Arg Thr Met
210 215 220
Lys Glu Asp Leu Glu Ala Val Val Glu Arg Leu Lys Pro Leu Phe Pro
225 230 235 240
Ala Glu Phe Gly Val Val Ala Ala Tyr Ala Glu Ser Tyr His Gln His
245 250 255
Phe Ala Ala His Leu Ala Ala Val Ala Gln Phe Glu Leu Cys Glu Arg
260 265 270
Asp Thr Tyr Met Leu Leu Leu Trp Val Gln Asn Leu Tyr Pro Asn Asp
275 280 285
Ile Ile Asn Ser Pro Lys Leu Val Gly Glu Leu Gln Gly Met Gly Leu
290 295 300
Gly Ser Leu Leu Pro Pro Arg Gln Ile Arg Leu Leu Glu Ala Thr Phe
305 310 315 320
Leu Ser Ser Glu Ala Ala Asn Val Arg Glu Leu Met Asp Arg Ala Leu
325 330 335
Glu Leu Glu Ala Arg Arg Trp Ala Glu Asp Val Pro Pro Gln Arg Leu
340 345 350
Asp Gly His Cys His Ser Glu Leu Ala Ile Asp Ile Ile Gln Ile Thr
355 360 365
Ser Gln Ala Gln Ala Lys Ala Glu Ser Ile Thr Leu Asp Leu Gly Ser
370 375 380
Gln Ile Lys Arg Val Leu Leu Val Glu Leu Pro Ala Phe Leu Arg Ser
385 390 395 400
Tyr Gln Arg Ala Phe Asn Glu Phe Leu Glu Arg Gly Lys Gln Leu Thr
405 410 415
Asn Tyr Arg Ala Asn Val Ile Ala Asn Ile Asn Asn Cys Leu Ser Phe
420 425 430
Arg Met Ser Met Glu Gln Asn Trp Gln Val Pro Gln Asp Thr Leu Ser
435 440 445
Leu Leu Leu Gly Pro Leu Gly Glu Leu Lys Ser His Gly Phe Asp Thr
450 455 460
Leu Leu Gln Asn Leu His Glu Asp Leu Lys Pro Leu Phe Lys Arg Phe
465 470 475 480
Thr His Thr Arg Trp Ala Ala Pro Val Glu Thr Leu Glu Asn Ile Ile
485 490 495
Ala Thr Val Asp Thr Arg Leu Pro Glu Phe Ser Glu Leu Gln Gly Cys
500 505 510
Phe Arg Glu Glu Leu Met Glu Ala Leu His Leu His Leu Val Lys Glu
515 520 525
Tyr Ile Ile Gln Leu Ser Lys Gly Arg Leu Val Leu Lys Thr Ala Glu
530 535 540
Gln Gln Gln Gln Leu Ala Gly Tyr Ile Leu Ala Asn Ala Asp Thr Ile
545 550 555 560
Gln His Phe Cys Thr Gln His Gly Ser Pro Ala Thr Trp Leu Gln Pro
565 570 575
Ala Leu Pro Thr Leu Ala Glu Ile Ile Arg Leu Gln Asp Pro Ser Ala
580 585 590
Ile Lys Ile Glu Val Ala Thr Tyr Ala Thr Cys Tyr Pro Asp Phe Ser
595 600 605
Lys Gly His Leu Ser Ala Ile Leu Ala Ile Lys Gly Asn Leu Ser Asn
610 615 620
Ser Glu Val Lys Arg Ile Arg Ser Ile Leu Asp Val Ser Met Gly Ala
625 630 635 640
Gln Glu Pro Ser Arg Pro Leu Phe Ser Leu Ile Lys Val Gly
645 650
<210> 36
<211> 99
<212> PRT
<213> NP_000575.1 interleukin-8 precursor (IL8) [Homo sapiens]
<400> 36
Met Thr Ser Lys Leu Ala Val Ala Leu Leu Ala Ala Phe Leu Ile Ser
1 5 10 15
Ala Ala Leu Cys Glu Gly Ala Val Leu Pro Arg Ser Ala Lys Glu Leu
20 25 30
Arg Cys Gln Cys Ile Lys Thr Tyr Ser Lys Pro Phe His Pro Lys Phe
35 40 45
Ile Lys Glu Leu Arg Val Ile Glu Ser Gly Pro His Cys Ala Asn Thr
50 55 60
Glu Ile Ile Val Lys Leu Ser Asp Gly Arg Glu Leu Cys Leu Asp Pro
65 70 75 80
Lys Glu Asn Trp Val Gln Arg Val Val Glu Lys Phe Leu Lys Arg Ala
85 90 95
Glu Asn Ser
<210> 37
<211> 136
<212> PRT
<213> NP_001305024.1 interleukin-6 isoform 2 (IL6) [Homo sapiens]
<400> 37
Met Cys Glu Ser Ser Lys Glu Ala Leu Ala Glu Asn Asn Leu Asn Leu
1 5 10 15
Pro Lys Met Ala Glu Lys Asp Gly Cys Phe Gln Ser Gly Phe Asn Glu
20 25 30
Glu Thr Cys Leu Val Lys Ile Ile Thr Gly Leu Leu Glu Phe Glu Val
35 40 45
Tyr Leu Glu Tyr Leu Gln Asn Arg Phe Glu Ser Ser Glu Glu Gln Ala
50 55 60
Arg Ala Val Gln Met Ser Thr Lys Val Leu Ile Gln Phe Leu Gln Lys
65 70 75 80
Lys Ala Lys Asn Leu Asp Ala Ile Thr Thr Pro Asp Pro Thr Thr Asn
85 90 95
Ala Ser Leu Leu Thr Lys Leu Gln Ala Gln Asn Gln Trp Leu Gln Asp
100 105 110
Met Thr Thr His Leu Ile Leu Arg Ser Phe Lys Glu Phe Leu Gln Ser
115 120 125
Ser Leu Arg Ala Leu Arg Gln Met
130 135
<210> 38
<211> 969
<212> PRT
<213> CAB94757.1 NFKB1 [Homo sapiens]
<400> 38
Met Ala Glu Asp Asp Pro Tyr Leu Gly Arg Pro Glu Gln Met Phe His
1 5 10 15
Leu Asp Pro Ser Leu Thr His Thr Ile Phe Asn Pro Glu Val Phe Gln
20 25 30
Pro Gln Met Ala Leu Pro Thr Asp Gly Pro Tyr Leu Gln Ile Leu Glu
35 40 45
Gln Pro Lys Gln Arg Gly Phe Arg Phe Arg Tyr Val Cys Glu Gly Pro
50 55 60
Ser His Gly Gly Leu Pro Gly Ala Ser Ser Glu Lys Asn Lys Lys Ser
65 70 75 80
Tyr Pro Gln Val Lys Ile Cys Asn Tyr Val Gly Pro Ala Lys Val Ile
85 90 95
Val Gln Leu Val Thr Asn Gly Lys Asn Ile His Leu His Ala His Ser
100 105 110
Leu Val Gly Lys His Cys Glu Asp Gly Ile Cys Thr Val Thr Ala Gly
115 120 125
Pro Lys Asp Met Val Val Gly Phe Ala Asn Leu Gly Ile Leu His Val
130 135 140
Thr Lys Lys Lys Val Phe Glu Thr Leu Glu Ala Arg Met Thr Glu Ala
145 150 155 160
Cys Ile Arg Gly Tyr Asn Pro Gly Leu Leu Val His Pro Asp Leu Ala
165 170 175
Tyr Leu Gln Ala Glu Gly Gly Gly Asp Arg Gln Leu Gly Asp Arg Glu
180 185 190
Lys Glu Leu Ile Arg Gln Ala Ala Leu Gln Gln Thr Lys Glu Met Asp
195 200 205
Leu Ser Val Val Arg Leu Met Phe Thr Ala Phe Leu Pro Asp Ser Thr
210 215 220
Gly Ser Phe Thr Arg Arg Leu Glu Pro Val Val Ser Asp Ala Ile Tyr
225 230 235 240
Asp Ser Ser Glu Ala Pro Asn Ala Ser Asn Leu Lys Ile Val Arg Met
245 250 255
Asp Arg Thr Ala Gly Cys Val Thr Gly Gly Glu Glu Ile Tyr Leu Leu
260 265 270
Cys Asp Lys Val Gln Lys Asp Asp Ile Gln Ile Arg Phe Tyr Glu Glu
275 280 285
Glu Glu Asn Gly Gly Val Trp Glu Gly Phe Gly Asp Phe Ser Pro Thr
290 295 300
Asp Val His Arg Gln Phe Ala Ile Val Phe Lys Thr Pro Lys Tyr Lys
305 310 315 320
Asp Ile Asn Ile Thr Lys Pro Ala Ser Val Phe Val Gln Leu Arg Arg
325 330 335
Lys Ser Asp Leu Glu Thr Ser Glu Pro Lys Pro Phe Leu Tyr Tyr Pro
340 345 350
Glu Ile Lys Asp Lys Glu Glu Val Gln Arg Lys Arg Gln Lys Leu Met
355 360 365
Pro Asn Phe Ser Asp Ser Phe Gly Gly Gly Ser Gly Ala Gly Ala Gly
370 375 380
Gly Gly Gly Met Phe Gly Ser Gly Gly Gly Gly Gly Gly Thr Gly Ser
385 390 395 400
Thr Gly Pro Gly Tyr Ser Phe Pro His Tyr Gly Phe Pro Thr Tyr Gly
405 410 415
Gly Ile Thr Phe His Pro Gly Thr Thr Lys Ser Asn Ala Gly Met Lys
420 425 430
His Gly Thr Met Asp Thr Glu Ser Lys Lys Asp Pro Glu Gly Cys Asp
435 440 445
Lys Ser Asp Asp Lys Asn Thr Val Asn Leu Phe Gly Lys Val Ile Glu
450 455 460
Thr Thr Glu Gln Asp Gln Glu Pro Ser Glu Ala Thr Val Gly Asn Gly
465 470 475 480
Glu Val Thr Leu Thr Tyr Ala Thr Gly Thr Lys Glu Glu Ser Ala Gly
485 490 495
Val Gln Asp Asn Leu Phe Leu Glu Lys Ala Met Gln Leu Ala Lys Arg
500 505 510
His Ala Asn Ala Leu Phe Asp Tyr Ala Val Thr Gly Asp Val Lys Met
515 520 525
Leu Leu Ala Val Gln Arg His Leu Thr Ala Val Gln Asp Glu Asn Gly
530 535 540
Asp Ser Val Leu His Leu Ala Ser Ser His Leu His Ser Gln Leu Val
545 550 555 560
Arg Asp Leu Leu Glu Val Thr Ser Gly Leu Ile Ser Asp Asp Ile Ile
565 570 575
Asn Met Arg Asn Asp Leu Tyr Gln Thr Pro Leu His Leu Ala Val Ile
580 585 590
Thr Lys Gln Glu Asp Val Val Glu Asp Leu Leu Arg Ala Gly Ala Asp
595 600 605
Leu Ser Leu Leu Asp Arg Leu Gly Asn Ser Val Leu His Leu Ala Ala
610 615 620
Lys Glu Gly His Asp Lys Val Leu Ser Ile Leu Leu Lys His Lys Lys
625 630 635 640
Ala Ala Leu Leu Leu Asp His Pro Asn Gly Asp Gly Leu Asn Ala Ile
645 650 655
His Leu Ala Met Met Ser Asn Ser Leu Pro Cys Leu Leu Leu Leu Val
660 665 670
Ala Ala Gly Ala Asp Val Asn Ala Gln Glu Gln Lys Ser Gly Arg Thr
675 680 685
Ala Leu His Leu Ala Val Glu His Asp Asn Ile Ser Leu Ala Gly Cys
690 695 700
Leu Leu Leu Glu Gly Asp Ala His Val Asp Ser Thr Thr Tyr Asp Gly
705 710 715 720
Thr Thr Pro Leu His Ile Val Ala Gly Arg Gly Ser Thr Arg Leu Ala
725 730 735
Ala Leu Leu Lys Ala Ala Gly Ala Asp Pro Leu Val Glu Asn Phe Glu
740 745 750
Pro Leu Tyr Asp Leu Asp Asp Ser Trp Glu Asn Ala Gly Glu Asp Glu
755 760 765
Gly Val Val Pro Gly Thr Thr Pro Leu Asp Met Ala Thr Ser Trp Gln
770 775 780
Val Phe Asp Ile Leu Asn Gly Lys Pro Tyr Glu Pro Glu Phe Thr Ser
785 790 795 800
Asp Asp Leu Leu Ala Gln Gly Asp Met Lys Gln Leu Ala Glu Asp Val
805 810 815
Lys Leu Gln Leu Tyr Lys Leu Leu Glu Ile Pro Asp Pro Asp Lys Asn
820 825 830
Trp Ala Thr Leu Ala Gln Lys Leu Gly Leu Gly Ile Leu Asn Asn Ala
835 840 845
Phe Arg Leu Ser Pro Ala Pro Ser Lys Thr Leu Met Asp Asn Tyr Glu
850 855 860
Val Ser Gly Gly Thr Ile Arg Glu Leu Val Glu Ala Leu Arg Gln Met
865 870 875 880
Gly Tyr Thr Glu Ala Ile Glu Val Ile Gln Ala Ala Ser Ser Pro Val
885 890 895
Lys Thr Thr Ser Gln Ala His Ser Leu Pro Leu Ser Pro Ala Ser Thr
900 905 910
Arg Gln Gln Ile Asp Glu Leu Arg Asp Ser Asp Ser Val Cys Asp Thr
915 920 925
Gly Val Glu Thr Ser Phe Arg Lys Leu Ser Phe Thr Glu Ser Leu Thr
930 935 940
Ser Gly Ala Ser Leu Leu Thr Leu Asn Lys Met Pro His Asp Tyr Gly
945 950 955 960
Gln Glu Gly Pro Leu Glu Gly Lys Ile
965
<210> 39
<211> 103
<212> PRT
<213> NP_056529.1 G0/G1 switch protein 2 (G0S2) [Homo sapiens]
<400> 39
Met Glu Thr Val Gln Glu Leu Ile Pro Leu Ala Lys Glu Met Met Ala
1 5 10 15
Gln Lys Arg Lys Gly Lys Met Val Lys Leu Tyr Val Leu Gly Ser Val
20 25 30
Leu Ala Leu Phe Gly Val Val Leu Gly Leu Met Glu Thr Val Cys Ser
35 40 45
Pro Phe Thr Ala Ala Arg Arg Leu Arg Asp Gln Glu Ala Ala Val Ala
50 55 60
Glu Leu Gln Ala Ala Leu Glu Arg Gln Ala Leu Gln Lys Gln Ala Leu
65 70 75 80
Gln Glu Lys Gly Lys Gln Gln Asp Thr Val Leu Gly Gly Arg Ala Leu
85 90 95
Ser Asn Arg Gln His Ala Ser
100
<210> 40
<211> 532
<212> PRT
<213> AAH15969.1 Intercellular adhesion molecule 1 (ICM1) [Homo sapiens]
<400> 40
Met Ala Pro Ser Ser Pro Arg Pro Ala Leu Pro Ala Leu Leu Val Leu
1 5 10 15
Leu Gly Ala Leu Phe Pro Gly Pro Gly Asn Ala Gln Thr Ser Val Ser
20 25 30
Pro Ser Lys Val Ile Leu Pro Arg Gly Gly Ser Val Leu Val Thr Cys
35 40 45
Ser Thr Ser Cys Asp Gln Pro Lys Leu Leu Gly Ile Glu Thr Pro Leu
50 55 60
Pro Lys Lys Glu Leu Leu Leu Pro Gly Asn Asn Arg Lys Val Tyr Glu
65 70 75 80
Leu Ser Asn Val Gln Glu Asp Ser Gln Pro Met Cys Tyr Ser Asn Cys
85 90 95
Pro Asp Gly Gln Ser Thr Ala Lys Thr Phe Leu Thr Val Tyr Trp Thr
100 105 110
Pro Glu Arg Val Glu Leu Ala Pro Leu Pro Ser Trp Gln Pro Val Gly
115 120 125
Lys Asn Leu Thr Leu Arg Cys Gln Val Glu Gly Gly Ala Pro Arg Ala
130 135 140
Asn Leu Thr Val Val Leu Leu Arg Gly Glu Lys Glu Leu Lys Arg Glu
145 150 155 160
Pro Ala Val Gly Glu Pro Ala Glu Val Thr Thr Thr Val Leu Val Arg
165 170 175
Arg Asp His His Gly Ala Asn Phe Ser Cys Arg Thr Glu Leu Asp Leu
180 185 190
Arg Pro Gln Gly Leu Glu Leu Phe Glu Asn Thr Ser Ala Pro Tyr Gln
195 200 205
Leu Gln Thr Phe Val Leu Pro Ala Thr Pro Pro Gln Leu Val Ser Pro
210 215 220
Arg Val Leu Glu Val Asp Thr Gln Gly Thr Val Val Cys Ser Leu Asp
225 230 235 240
Gly Leu Phe Pro Val Ser Glu Ala Gln Val His Leu Ala Leu Gly Asp
245 250 255
Gln Arg Leu Asn Pro Thr Val Thr Tyr Gly Asn Asp Ser Phe Ser Ala
260 265 270
Lys Ala Ser Val Ser Val Thr Ala Glu Asp Glu Gly Thr Gln Arg Leu
275 280 285
Thr Cys Ala Val Ile Leu Gly Asn Gln Ser Gln Glu Thr Leu Gln Thr
290 295 300
Val Thr Ile Tyr Ser Phe Pro Ala Pro Asn Val Ile Leu Thr Lys Pro
305 310 315 320
Glu Val Ser Glu Gly Thr Glu Val Thr Val Lys Cys Glu Ala His Pro
325 330 335
Arg Ala Lys Val Thr Leu Asn Gly Val Pro Ala Gln Pro Leu Gly Pro
340 345 350
Arg Ala Gln Leu Leu Leu Lys Ala Thr Pro Glu Asp Asn Gly Arg Ser
355 360 365
Phe Ser Cys Ser Ala Thr Leu Glu Val Ala Gly Gln Leu Ile His Lys
370 375 380
Asn Gln Thr Arg Glu Leu Arg Val Leu Tyr Gly Pro Arg Leu Asp Glu
385 390 395 400
Arg Asp Cys Pro Gly Asn Trp Thr Trp Pro Glu Asn Ser Gln Gln Thr
405 410 415
Pro Met Cys Gln Ala Trp Gly Asn Pro Leu Pro Glu Leu Lys Cys Leu
420 425 430
Lys Asp Gly Thr Phe Pro Leu Pro Ile Gly Glu Ser Val Thr Val Thr
435 440 445
Arg Asp Leu Glu Gly Thr Tyr Leu Cys Arg Ala Arg Ser Thr Gln Gly
450 455 460
Glu Val Thr Arg Lys Val Thr Val Asn Val Leu Ser Pro Arg Tyr Glu
465 470 475 480
Ile Val Ile Ile Thr Val Val Ala Ala Ala Val Ile Met Gly Thr Ala
485 490 495
Gly Leu Ser Thr Tyr Leu Tyr Asn Arg Gln Arg Lys Ile Lys Lys Tyr
500 505 510
Arg Leu Gln Gln Ala Gln Lys Gly Thr Pro Met Lys Pro Asn Thr Gln
515 520 525
Ala Thr Pro Pro
530
<210> 41
<211> 275
<212> PRT
<213> AAH03097.1 Intercellular adhesion molecule 2 (ICM2) [Homo sapiens]
<400> 41
Met Ser Ser Phe Gly Tyr Arg Thr Leu Thr Val Ala Leu Phe Thr Leu
1 5 10 15
Ile Cys Cys Pro Gly Ser Asp Glu Lys Val Phe Glu Val His Val Arg
20 25 30
Pro Lys Lys Leu Ala Val Glu Pro Lys Gly Ser Leu Glu Val Asn Cys
35 40 45
Ser Thr Thr Cys Asn Gln Pro Glu Val Gly Gly Leu Glu Thr Ser Leu
50 55 60
Asp Lys Ile Leu Leu Asp Glu Gln Ala Gln Trp Lys His Tyr Leu Val
65 70 75 80
Ser Asn Ile Ser His Asp Thr Val Leu Gln Cys His Phe Thr Cys Ser
85 90 95
Gly Lys Gln Glu Ser Met Asn Ser Asn Val Ser Val Tyr Gln Pro Pro
100 105 110
Arg Gln Val Ile Leu Thr Leu Gln Pro Thr Leu Val Ala Val Gly Lys
115 120 125
Ser Phe Thr Ile Glu Cys Arg Val Pro Thr Val Glu Pro Leu Asp Ser
130 135 140
Leu Thr Leu Phe Leu Phe Arg Gly Asn Glu Thr Leu His Tyr Glu Thr
145 150 155 160
Phe Gly Lys Ala Ala Pro Ala Pro Gln Glu Ala Thr Ala Thr Phe Asn
165 170 175
Ser Thr Ala Asp Arg Glu Asp Gly His Arg Asn Phe Ser Cys Leu Ala
180 185 190
Val Leu Asp Leu Met Ser Arg Gly Gly Asn Ile Phe His Lys His Ser
195 200 205
Ala Pro Lys Met Leu Glu Ile Tyr Glu Pro Val Ser Asp Ser Gln Met
210 215 220
Val Ile Ile Val Thr Val Val Ser Val Leu Leu Ser Leu Phe Val Thr
225 230 235 240
Ser Val Leu Leu Cys Phe Ile Phe Gly Gln His Leu Arg Gln Gln Arg
245 250 255
Met Gly Thr Tyr Gly Val Arg Ala Ala Trp Arg Arg Leu Pro Gln Ala
260 265 270
Phe Arg Pro
275
<210> 42
<211> 547
<212> PRT
<213> AAH58903.1 Intercellular adhesion molecule 3 (ICM3) [Homo sapiens]
<400> 42
Met Ala Thr Met Val Pro Ser Val Leu Trp Pro Arg Ala Cys Trp Thr
1 5 10 15
Leu Leu Val Cys Cys Leu Leu Thr Pro Gly Val Gln Gly Gln Glu Phe
20 25 30
Leu Leu Arg Val Glu Pro Gln Asn Pro Val Leu Ser Ala Gly Gly Ser
35 40 45
Leu Phe Val Asn Cys Ser Thr Asp Cys Pro Ser Ser Glu Lys Ile Ala
50 55 60
Leu Glu Thr Ser Leu Ser Lys Glu Leu Val Ala Ser Gly Met Gly Trp
65 70 75 80
Ala Ala Phe Asn Leu Ser Asn Val Thr Gly Asn Ser Arg Ile Leu Cys
85 90 95
Ser Val Tyr Cys Asn Gly Ser Gln Ile Thr Gly Ser Ser Asn Ile Thr
100 105 110
Val Tyr Arg Leu Pro Glu Arg Val Glu Leu Ala Pro Leu Pro Pro Trp
115 120 125
Gln Pro Val Gly Gln Asn Phe Thr Leu Arg Cys Gln Val Glu Asp Gly
130 135 140
Ser Pro Arg Thr Ser Leu Thr Val Val Leu Leu Arg Trp Glu Glu Glu
145 150 155 160
Leu Ser Arg Gln Pro Ala Val Glu Glu Pro Ala Glu Val Thr Ala Thr
165 170 175
Val Leu Ala Ser Arg Asp Asp His Gly Ala Pro Phe Ser Cys Arg Thr
180 185 190
Glu Leu Asp Met Gln Pro Gln Gly Leu Gly Leu Phe Val Asn Thr Ser
195 200 205
Ala Pro Arg Gln Leu Arg Thr Phe Val Leu Pro Val Thr Pro Pro Arg
210 215 220
Leu Val Ala Pro Arg Phe Leu Glu Val Glu Thr Ser Trp Pro Val Asp
225 230 235 240
Cys Thr Leu Asp Gly Leu Phe Pro Ala Ser Glu Ala Gln Val Tyr Leu
245 250 255
Ala Leu Gly Asp Gln Met Leu Asn Ala Thr Val Met Asn His Gly Asp
260 265 270
Thr Leu Thr Ala Thr Ala Thr Ala Thr Ala Arg Ala Asp Gln Glu Gly
275 280 285
Ala Arg Glu Ile Val Cys Asn Val Thr Leu Gly Gly Glu Arg Arg Glu
290 295 300
Ala Arg Glu Asn Leu Thr Val Phe Ser Phe Leu Gly Pro Ile Val Asn
305 310 315 320
Leu Ser Glu Pro Thr Ala His Glu Gly Ser Thr Val Thr Val Ser Cys
325 330 335
Met Ala Gly Ala Arg Val Gln Val Thr Leu Asp Gly Val Pro Ala Ala
340 345 350
Ala Pro Gly Gln Pro Ala Gln Leu Gln Leu Asn Ala Thr Glu Ser Asp
355 360 365
Asp Gly Arg Ser Phe Phe Cys Ser Ala Thr Leu Glu Val Asp Gly Glu
370 375 380
Phe Leu His Arg Asn Ser Ser Val Gln Leu Arg Val Leu Tyr Gly Pro
385 390 395 400
Lys Ile Asp Arg Ala Thr Cys Pro Gln His Leu Lys Trp Lys Asp Lys
405 410 415
Thr Arg His Val Leu Gln Cys Gln Ala Arg Gly Asn Pro Tyr Pro Glu
420 425 430
Leu Arg Cys Leu Lys Glu Gly Ser Ser Arg Glu Val Pro Val Gly Ile
435 440 445
Pro Phe Phe Val Asn Val Thr His Asn Gly Thr Tyr Gln Cys Gln Ala
450 455 460
Ser Ser Ser Arg Gly Lys Tyr Thr Leu Val Val Val Met Asp Ile Glu
465 470 475 480
Ala Gly Ser Ser His Phe Val Pro Val Phe Val Ala Val Leu Leu Thr
485 490 495
Leu Gly Val Val Thr Ile Val Leu Ala Leu Met Tyr Val Phe Arg Glu
500 505 510
His Gln Arg Ser Gly Ser Tyr His Val Arg Glu Glu Ser Thr Tyr Leu
515 520 525
Pro Leu Thr Ser Met Gln Pro Thr Glu Ala Met Gly Glu Glu Pro Ser
530 535 540
Arg Ala Glu
545
<210> 43
<211> 152
<212> PRT
<213> AAH08280.1 Prostaglandin E synthase (PTGES) [Homo sapiens]
<400> 43
Met Pro Ala His Ser Leu Val Met Ser Ser Pro Ala Leu Pro Ala Phe
1 5 10 15
Leu Leu Cys Ser Thr Leu Leu Val Ile Lys Met Tyr Val Val Ala Ile
20 25 30
Ile Thr Gly Gln Val Arg Leu Arg Lys Lys Ala Phe Ala Asn Pro Glu
35 40 45
Asp Ala Leu Arg His Gly Gly Pro Gln Tyr Cys Arg Ser Asp Pro Asp
50 55 60
Val Glu Arg Cys Leu Arg Ala His Arg Asn Asp Met Glu Thr Ile Tyr
65 70 75 80
Pro Phe Leu Phe Leu Gly Phe Val Tyr Ser Phe Leu Gly Pro Asn Pro
85 90 95
Phe Val Ala Trp Met His Phe Leu Val Phe Leu Val Gly Arg Val Ala
100 105 110
His Thr Val Ala Tyr Leu Gly Lys Leu Arg Ala Pro Ile Arg Ser Val
115 120 125
Thr Tyr Thr Leu Ala Gln Leu Pro Cys Ala Ser Met Ala Leu Gln Ile
130 135 140
Leu Trp Glu Ala Ala Arg His Leu
145 150
<210> 44
<211> 136
<212> PRT
<213> AAH32663.1 PMAIP1 protein (PMAIP1) [Homo sapiens]
<400> 44
Met Pro Gly Lys Lys Ala Arg Lys Asn Ala Gln Pro Ser Pro Ala Arg
1 5 10 15
Ala Pro Ala Gly Pro Ala Gly Thr Ala Gly Thr Ala Arg Asp Gln Ala
20 25 30
Gly Phe Ala Ile Gly Met Gln Leu Arg Phe Thr Arg Gly Lys Lys Leu
35 40 45
Leu Ser Ser Ser Leu Ser Ser Ser Pro Leu Ala Leu Pro Arg Gly His
50 55 60
Glu Glu Gln Val Gln Val Ala Gly Ser Arg Val Cys Tyr Ser Thr Gln
65 70 75 80
Glu Ile Trp Arg Gln Thr Glu Leu Pro Ala Glu Thr Ser Glu Ser Asp
85 90 95
Ile Gln Thr Leu Leu Leu Arg Asn Leu Thr Ala Ser Lys Thr Cys Met
100 105 110
Arg Gly Leu Leu Gln Lys Ser Phe Leu Arg Arg Cys Thr Phe His Gln
115 120 125
Phe Glu Glu Arg Leu His Cys Asn
130 135
<210> 45
<211> 502
<212> PRT
<213> AAH00669.1 Spermine oxidase (SMOX) [Homo sapiens]
<400> 45
Met Gln Ser Cys Glu Ser Ser Gly Asp Ser Ala Asp Asp Pro Leu Ser
1 5 10 15
Arg Gly Leu Arg Arg Arg Gly Gln Pro Arg Val Val Val Ile Gly Ala
20 25 30
Gly Leu Ala Gly Leu Ala Ala Ala Lys Ala Leu Leu Glu Gln Gly Phe
35 40 45
Thr Asp Val Thr Val Leu Glu Ala Ser Ser His Ile Gly Gly Arg Val
50 55 60
Gln Ser Val Lys Leu Gly His Ala Thr Phe Glu Leu Gly Ala Thr Trp
65 70 75 80
Ile His Gly Ser His Gly Asn Pro Ile Tyr His Leu Ala Glu Ala Asn
85 90 95
Gly Leu Leu Glu Glu Thr Thr Asp Gly Glu Arg Ser Val Gly Arg Ile
100 105 110
Ser Leu Tyr Ser Lys Asn Gly Val Ala Cys Tyr Leu Thr Asn His Gly
115 120 125
Arg Arg Ile Pro Lys Asp Val Val Glu Glu Phe Ser Asp Leu Tyr Asn
130 135 140
Glu Val Tyr Asn Leu Thr Gln Glu Phe Phe Arg His Asp Lys Pro Val
145 150 155 160
Asn Ala Glu Ser Gln Asn Ser Val Gly Val Phe Thr Arg Glu Glu Val
165 170 175
Arg Asn Arg Ile Arg Asn Asp Pro Asp Asp Pro Glu Ala Thr Lys Arg
180 185 190
Leu Lys Leu Ala Met Ile Gln Gln Tyr Leu Lys Val Glu Ser Cys Glu
195 200 205
Ser Ser Ser His Ser Met Asp Glu Val Ser Leu Ser Ala Phe Gly Glu
210 215 220
Trp Thr Glu Ile Pro Gly Ala His His Ile Ile Pro Ser Gly Phe Met
225 230 235 240
Arg Val Val Glu Leu Leu Ala Glu Gly Ile Pro Ala His Val Ile Gln
245 250 255
Leu Gly Lys Pro Val Arg Cys Ile His Trp Asp Gln Ala Ser Ala Arg
260 265 270
Pro Arg Gly Pro Glu Ile Glu Pro Arg Gly Val Leu Lys Arg Gln Tyr
275 280 285
Thr Ser Phe Phe Arg Pro Gly Leu Pro Thr Glu Lys Val Ala Ala Ile
290 295 300
His Arg Leu Gly Ile Gly Thr Thr Asp Lys Ile Phe Leu Glu Phe Glu
305 310 315 320
Glu Pro Phe Trp Gly Pro Glu Cys Asn Ser Leu Gln Phe Val Trp Glu
325 330 335
Asp Glu Ala Glu Ser His Thr Leu Thr Tyr Pro Pro Glu Leu Trp Tyr
340 345 350
Arg Lys Ile Cys Gly Phe Asp Val Leu Tyr Pro Pro Glu Arg Tyr Gly
355 360 365
His Val Leu Ser Gly Trp Ile Cys Gly Glu Glu Ala Leu Val Met Glu
370 375 380
Lys Cys Asp Asp Glu Ala Val Ala Glu Ile Cys Thr Glu Met Leu Arg
385 390 395 400
Gln Phe Thr Gly Asn Pro Asn Ile Pro Lys Pro Arg Arg Ile Leu Arg
405 410 415
Ser Ala Trp Gly Ser Asn Pro Tyr Phe Arg Gly Ser Tyr Ser Tyr Thr
420 425 430
Gln Val Gly Ser Ser Gly Ala Asp Val Glu Lys Leu Ala Lys Pro Leu
435 440 445
Pro Tyr Thr Glu Ser Ser Lys Thr Ala Pro Met Gln Val Leu Phe Ser
450 455 460
Gly Glu Ala Thr His Arg Lys Tyr Tyr Ser Thr Thr His Gly Ala Leu
465 470 475 480
Leu Ser Gly Gln Arg Glu Ala Ala Arg Leu Ile Glu Met Tyr Arg Asp
485 490 495
Leu Phe Gln Gln Gly Thr
500
<210> 46
<211> 277
<212> PRT
<213> AAH30205.1 Tumor necrosis factor, alpha-induced protein 6 (TNFAIP6) [Homo sapiens]
<400> 46
Met Ile Ile Leu Ile Tyr Leu Phe Leu Leu Leu Trp Glu Asp Thr Gln
1 5 10 15
Gly Trp Gly Phe Lys Asp Gly Ile Phe His Asn Ser Ile Trp Leu Glu
20 25 30
Arg Ala Ala Gly Val Tyr His Arg Glu Ala Arg Ser Gly Lys Tyr Lys
35 40 45
Leu Thr Tyr Ala Glu Ala Lys Ala Val Cys Glu Phe Glu Gly Gly His
50 55 60
Leu Ala Thr Tyr Lys Gln Leu Glu Ala Ala Arg Lys Ile Gly Phe His
65 70 75 80
Val Cys Ala Ala Gly Trp Met Ala Lys Gly Arg Val Gly Tyr Pro Ile
85 90 95
Val Lys Pro Gly Pro Asn Cys Gly Phe Gly Lys Thr Gly Ile Ile Asp
100 105 110
Tyr Gly Ile Arg Leu Asn Arg Ser Glu Arg Trp Asp Ala Tyr Cys Tyr
115 120 125
Asn Pro His Ala Lys Glu Cys Gly Gly Val Phe Thr Asp Pro Lys Gln
130 135 140
Ile Phe Lys Ser Pro Gly Phe Pro Asn Glu Tyr Glu Asp Asn Gln Ile
145 150 155 160
Cys Tyr Trp His Ile Arg Leu Lys Tyr Gly Gln Arg Ile His Leu Ser
165 170 175
Phe Leu Asp Phe Asp Leu Glu Asp Asp Pro Gly Cys Leu Ala Asp Tyr
180 185 190
Val Glu Ile Tyr Asp Ser Tyr Asp Asp Val His Gly Phe Val Gly Arg
195 200 205
Tyr Cys Gly Asp Glu Leu Pro Asp Asp Ile Ile Ser Thr Gly Asn Val
210 215 220
Met Thr Leu Lys Phe Leu Ser Asp Ala Ser Val Thr Ala Gly Gly Phe
225 230 235 240
Gln Ile Lys Tyr Val Ala Met Asp Pro Val Ser Lys Ser Ser Gln Gly
245 250 255
Lys Asn Thr Ser Thr Thr Ser Thr Gly Asn Lys Asn Phe Leu Ala Gly
260 265 270
Arg Phe Ser His Leu
275
<210> 47
<211> 477
<212> PRT
<213> AAH69716.1 Matrix metallopeptidase 3 (MMP) [Homo sapiens]
<400> 47
Met Lys Ser Leu Pro Ile Leu Leu Leu Leu Cys Val Ala Val Cys Ser
1 5 10 15
Ala Tyr Pro Leu Asp Gly Ala Ala Arg Gly Glu Asp Thr Ser Met Asn
20 25 30
Leu Val Gln Lys Tyr Leu Glu Asn Tyr Tyr Asp Leu Glu Lys Asp Val
35 40 45
Lys Gln Phe Val Arg Arg Lys Asp Ser Gly Pro Val Val Lys Lys Ile
50 55 60
Arg Glu Met Gln Lys Phe Leu Gly Leu Glu Val Thr Gly Lys Leu Asp
65 70 75 80
Ser Asp Thr Leu Glu Val Met Arg Lys Pro Arg Cys Gly Val Pro Asp
85 90 95
Val Gly His Phe Arg Thr Phe Pro Gly Ile Pro Lys Trp Arg Lys Thr
100 105 110
His Leu Thr Tyr Arg Ile Val Asn Tyr Thr Pro Asp Leu Pro Lys Asp
115 120 125
Ala Val Asp Ser Ala Val Glu Lys Ala Leu Lys Val Trp Glu Glu Val
130 135 140
Thr Pro Leu Thr Phe Ser Arg Leu Tyr Glu Gly Glu Ala Asp Ile Met
145 150 155 160
Ile Ser Phe Ala Val Arg Glu His Gly Asp Phe Tyr Pro Phe Asp Gly
165 170 175
Pro Gly Asn Val Leu Ala His Ala Tyr Ala Pro Gly Pro Gly Ile Asn
180 185 190
Gly Asp Ala His Phe Asp Asp Asp Glu Gln Trp Thr Lys Asp Thr Thr
195 200 205
Gly Thr Asn Leu Phe Leu Val Ala Ala His Glu Ile Gly His Ser Leu
210 215 220
Gly Leu Phe His Ser Ala Asn Thr Glu Ala Leu Met Tyr Pro Leu Tyr
225 230 235 240
His Ser Leu Thr Asp Leu Thr Arg Phe Arg Leu Ser Gln Asp Asp Ile
245 250 255
Asn Gly Ile Gln Ser Leu Tyr Gly Pro Pro Pro Asp Ser Pro Glu Thr
260 265 270
Pro Leu Val Pro Thr Glu Pro Val Pro Pro Glu Pro Gly Thr Pro Ala
275 280 285
Asn Cys Asp Pro Ala Leu Ser Phe Asp Ala Val Ser Thr Leu Arg Gly
290 295 300
Glu Ile Leu Ile Phe Lys Asp Arg His Phe Trp Arg Lys Ser Leu Arg
305 310 315 320
Lys Leu Glu Pro Glu Leu His Leu Ile Ser Ser Phe Trp Pro Ser Leu
325 330 335
Pro Ser Gly Val Asp Ala Ala Tyr Glu Val Thr Ser Lys Asp Leu Val
340 345 350
Phe Ile Phe Lys Gly Asn Gln Phe Trp Ala Ile Arg Gly Asn Glu Val
355 360 365
Arg Ala Gly Tyr Pro Arg Gly Ile His Thr Leu Gly Phe Pro Pro Thr
370 375 380
Val Arg Lys Ile Asp Ala Ala Ile Ser Asp Lys Glu Lys Asn Lys Thr
385 390 395 400
Tyr Phe Phe Val Glu Asp Lys Tyr Trp Arg Phe Asp Glu Lys Arg Asn
405 410 415
Ser Met Glu Pro Gly Phe Pro Lys Gln Ile Ala Glu Asp Phe Pro Gly
420 425 430
Ile Asp Ser Lys Ile Asp Ala Val Phe Glu Glu Phe Gly Phe Phe Tyr
435 440 445
Phe Phe Thr Gly Ser Ser Gln Leu Glu Phe Asp Pro Asn Ala Lys Lys
450 455 460
Val Thr His Thr Leu Lys Ser Asn Ser Trp Leu Asn Cys
465 470 475
<210> 48
<211> 490
<212> PRT
<213> AAH04977.1 IFIT3 [Homo sapiens]
<400> 48
Met Ser Glu Val Thr Lys Asn Ser Leu Glu Lys Ile Leu Pro Gln Leu
1 5 10 15
Lys Cys His Phe Thr Trp Asn Leu Phe Lys Glu Asp Ser Val Ser Arg
20 25 30
Asp Leu Glu Asp Arg Val Cys Asn Gln Ile Glu Ser Leu Asn Thr Glu
35 40 45
Phe Lys Ala Thr Met Tyr Asn Leu Leu Ala Tyr Ile Lys His Leu Asp
50 55 60
Gly Asn Asn Glu Ala Ala Leu Glu Cys Leu Arg Gln Ala Glu Glu Leu
65 70 75 80
Ile Gln Gln Glu His Ala Asp Gln Ala Glu Ile Arg Ser Leu Val Thr
85 90 95
Trp Gly Asn Tyr Ala Trp Val Tyr Tyr His Leu Gly Arg Leu Ser Asp
100 105 110
Ala Gln Ile Tyr Val Asp Lys Val Lys Gln Thr Cys Lys Lys Phe Ser
115 120 125
Asn Pro Tyr Ser Ile Glu Tyr Ser Glu Leu Asp Cys Glu Glu Gly Trp
130 135 140
Thr Gln Leu Lys Cys Gly Arg Asn Glu Arg Ala Lys Val Cys Phe Glu
145 150 155 160
Lys Ala Leu Glu Glu Lys Pro Asn Asn Pro Glu Phe Ser Ser Gly Leu
165 170 175
Ala Ile Ala Met Tyr His Leu Asp Asn His Pro Glu Lys Gln Phe Ser
180 185 190
Thr Asp Val Leu Lys Gln Ala Ile Glu Leu Ser Pro Asp Asn Gln Tyr
195 200 205
Val Lys Val Leu Leu Gly Leu Lys Leu Gln Lys Met Asn Lys Glu Ala
210 215 220
Glu Gly Glu Gln Phe Val Glu Glu Ala Leu Glu Lys Ser Pro Cys Gln
225 230 235 240
Thr Asp Val Leu Arg Ser Ala Ala Lys Phe Tyr Arg Arg Lys Gly Asp
245 250 255
Leu Asp Lys Ala Ile Glu Leu Phe Gln Arg Val Leu Glu Ser Thr Pro
260 265 270
Asn Asn Gly Tyr Leu Tyr His Gln Ile Gly Cys Cys Tyr Lys Ala Lys
275 280 285
Val Arg Gln Met Gln Asn Thr Gly Glu Ser Glu Ala Ser Gly Asn Lys
290 295 300
Glu Met Ile Glu Ala Leu Lys Gln Tyr Ala Met Asp Tyr Ser Asn Lys
305 310 315 320
Ala Leu Glu Lys Gly Leu Asn Pro Leu Asn Ala Tyr Ser Asp Leu Ala
325 330 335
Glu Phe Leu Glu Thr Glu Cys Tyr Gln Thr Pro Phe Asn Lys Glu Val
340 345 350
Pro Asp Ala Glu Lys Gln Gln Ser His Gln Arg Tyr Cys Asn Leu Gln
355 360 365
Lys Tyr Asn Gly Lys Ser Glu Asp Thr Ala Val Gln His Gly Leu Glu
370 375 380
Gly Leu Ser Ile Ser Lys Lys Ser Thr Asp Lys Glu Glu Ile Lys Asp
385 390 395 400
Gln Pro Gln Asn Val Ser Glu Asn Leu Leu Pro Gln Asn Ala Pro Asn
405 410 415
Tyr Trp Tyr Leu Gln Gly Leu Ile His Lys Gln Asn Gly Asp Leu Leu
420 425 430
Gln Ala Ala Lys Cys Tyr Glu Lys Glu Leu Gly Arg Leu Leu Arg Asp
435 440 445
Ala Pro Ser Gly Ile Gly Ser Ile Phe Leu Ser Ala Ser Glu Leu Glu
450 455 460
Asp Gly Ser Glu Glu Met Gly Gln Gly Ala Val Ser Ser Ser Pro Arg
465 470 475 480
Glu Leu Leu Ser Asn Ser Glu Gln Leu Asn
485 490
<210> 49
<211> 114
<212> PRT
<213> NP_002984.1 C-X-C motif chemokine 6 precursor (CXCL6) [Homo sapiens]
<400> 49
Met Ser Leu Pro Ser Ser Arg Ala Ala Arg Val Pro Gly Pro Ser Gly
1 5 10 15
Ser Leu Cys Ala Leu Leu Ala Leu Leu Leu Leu Leu Thr Pro Pro Gly
20 25 30
Pro Leu Ala Ser Ala Gly Pro Val Ser Ala Val Leu Thr Glu Leu Arg
35 40 45
Cys Thr Cys Leu Arg Val Thr Leu Arg Val Asn Pro Lys Thr Ile Gly
50 55 60
Lys Leu Gln Val Phe Pro Ala Gly Pro Gln Cys Ser Lys Val Glu Val
65 70 75 80
Val Ala Ser Leu Lys Asn Gly Lys Gln Val Cys Leu Asp Pro Glu Ala
85 90 95
Pro Phe Leu Lys Lys Val Ile Gln Lys Ile Leu Asp Ser Gly Asn Lys
100 105 110
Lys Asn
<210> 50
<211> 604
<212> PRT
<213> NP_892007.1 baculoviral IAP repeat-containing protein 3 (BIRC3) [Homo sapiens]
<400> 50
Met Asn Ile Val Glu Asn Ser Ile Phe Leu Ser Asn Leu Met Lys Ser
1 5 10 15
Ala Asn Thr Phe Glu Leu Lys Tyr Asp Leu Ser Cys Glu Leu Tyr Arg
20 25 30
Met Ser Thr Tyr Ser Thr Phe Pro Ala Gly Val Pro Val Ser Glu Arg
35 40 45
Ser Leu Ala Arg Ala Gly Phe Tyr Tyr Thr Gly Val Asn Asp Lys Val
50 55 60
Lys Cys Phe Cys Cys Gly Leu Met Leu Asp Asn Trp Lys Arg Gly Asp
65 70 75 80
Ser Pro Thr Glu Lys His Lys Lys Leu Tyr Pro Ser Cys Arg Phe Val
85 90 95
Gln Ser Leu Asn Ser Val Asn Asn Leu Glu Ala Thr Ser Gln Pro Thr
100 105 110
Phe Pro Ser Ser Val Thr Asn Ser Thr His Ser Leu Leu Pro Gly Thr
115 120 125
Glu Asn Ser Gly Tyr Phe Arg Gly Ser Tyr Ser Asn Ser Pro Ser Asn
130 135 140
Pro Val Asn Ser Arg Ala Asn Gln Asp Phe Ser Ala Leu Met Arg Ser
145 150 155 160
Ser Tyr His Cys Ala Met Asn Asn Glu Asn Ala Arg Leu Leu Thr Phe
165 170 175
Gln Thr Trp Pro Leu Thr Phe Leu Ser Pro Thr Asp Leu Ala Lys Ala
180 185 190
Gly Phe Tyr Tyr Ile Gly Pro Gly Asp Arg Val Ala Cys Phe Ala Cys
195 200 205
Gly Gly Lys Leu Ser Asn Trp Glu Pro Lys Asp Asn Ala Met Ser Glu
210 215 220
His Leu Arg His Phe Pro Lys Cys Pro Phe Ile Glu Asn Gln Leu Gln
225 230 235 240
Asp Thr Ser Arg Tyr Thr Val Ser Asn Leu Ser Met Gln Thr His Ala
245 250 255
Ala Arg Phe Lys Thr Phe Phe Asn Trp Pro Ser Ser Val Leu Val Asn
260 265 270
Pro Glu Gln Leu Ala Ser Ala Gly Phe Tyr Tyr Val Gly Asn Ser Asp
275 280 285
Asp Val Lys Cys Phe Cys Cys Asp Gly Gly Leu Arg Cys Trp Glu Ser
290 295 300
Gly Asp Asp Pro Trp Val Gln His Ala Lys Trp Phe Pro Arg Cys Glu
305 310 315 320
Tyr Leu Ile Arg Ile Lys Gly Gln Glu Phe Ile Arg Gln Val Gln Ala
325 330 335
Ser Tyr Pro His Leu Leu Glu Gln Leu Leu Ser Thr Ser Asp Ser Pro
340 345 350
Gly Asp Glu Asn Ala Glu Ser Ser Ile Ile His Phe Glu Pro Gly Glu
355 360 365
Asp His Ser Glu Asp Ala Ile Met Met Asn Thr Pro Val Ile Asn Ala
370 375 380
Ala Val Glu Met Gly Phe Ser Arg Ser Leu Val Lys Gln Thr Val Gln
385 390 395 400
Arg Lys Ile Leu Ala Thr Gly Glu Asn Tyr Arg Leu Val Asn Asp Leu
405 410 415
Val Leu Asp Leu Leu Asn Ala Glu Asp Glu Ile Arg Glu Glu Glu Arg
420 425 430
Glu Arg Ala Thr Glu Glu Lys Glu Ser Asn Asp Leu Leu Leu Ile Arg
435 440 445
Lys Asn Arg Met Ala Leu Phe Gln His Leu Thr Cys Val Ile Pro Ile
450 455 460
Leu Asp Ser Leu Leu Thr Ala Gly Ile Ile Asn Glu Gln Glu His Asp
465 470 475 480
Val Ile Lys Gln Lys Thr Gln Thr Ser Leu Gln Ala Arg Glu Leu Ile
485 490 495
Asp Thr Ile Leu Val Lys Gly Asn Ile Ala Ala Thr Val Phe Arg Asn
500 505 510
Ser Leu Gln Glu Ala Glu Ala Val Leu Tyr Glu His Leu Phe Val Gln
515 520 525
Gln Asp Ile Lys Tyr Ile Pro Thr Glu Asp Val Ser Asp Leu Pro Val
530 535 540
Glu Glu Gln Leu Arg Arg Leu Gln Glu Glu Arg Thr Cys Lys Val Cys
545 550 555 560
Met Asp Lys Glu Val Ser Ile Val Phe Ile Pro Cys Gly His Leu Val
565 570 575
Val Cys Lys Asp Cys Ala Pro Ser Leu Arg Lys Cys Pro Ile Cys Arg
580 585 590
Ser Thr Ile Lys Gly Thr Val Arg Thr Phe Leu Ser
595 600
<210> 51
<211> 175
<212> PRT
<213> CAG46735.1 BCL2A1 [Homo sapiens]
<400> 51
Met Thr Asp Cys Glu Phe Gly Tyr Ile Tyr Arg Leu Ala Gln Asp Tyr
1 5 10 15
Leu Gln Cys Val Leu Gln Ile Pro Gln Pro Gly Ser Gly Pro Ser Lys
20 25 30
Thr Ser Arg Val Leu Gln Asn Val Ala Phe Ser Val Gln Lys Glu Val
35 40 45
Glu Lys Asn Leu Lys Ser Cys Leu Asp Asn Val Asn Val Val Ser Val
50 55 60
Asp Thr Ala Arg Thr Leu Phe Asn Gln Val Met Glu Lys Glu Phe Glu
65 70 75 80
Asp Gly Ile Ile Asn Trp Gly Arg Ile Val Thr Ile Phe Ala Phe Glu
85 90 95
Gly Ile Leu Ile Lys Lys Leu Leu Arg Gln Gln Ile Ala Pro Asp Val
100 105 110
Asp Thr Tyr Lys Glu Ile Ser Tyr Phe Val Ala Glu Phe Ile Met Asn
115 120 125
Asn Thr Gly Glu Trp Ile Arg Gln Asn Gly Gly Trp Glu Asn Gly Phe
130 135 140
Val Lys Lys Phe Glu Pro Lys Ser Gly Trp Met Thr Phe Leu Glu Val
145 150 155 160
Thr Gly Lys Ile Cys Glu Met Leu Ser Leu Leu Lys Gln Tyr Cys
165 170 175
<210> 52
<211> 250
<212> PRT
<213> CAG38788.1 GCH1 [Homo sapiens]
<400> 52
Met Glu Lys Gly Pro Val Arg Ala Pro Ala Glu Lys Pro Arg Gly Ala
1 5 10 15
Arg Cys Ser Asn Gly Phe Pro Glu Arg Asp Pro Pro Arg Pro Gly Pro
20 25 30
Ser Arg Pro Ala Glu Lys Pro Pro Arg Pro Glu Ala Lys Ser Ala Gln
35 40 45
Pro Ala Asp Gly Trp Lys Gly Glu Arg Pro Arg Ser Glu Glu Asp Asn
50 55 60
Glu Leu Asn Leu Pro Asn Leu Ala Ala Ala Tyr Ser Ser Ile Leu Ser
65 70 75 80
Ser Leu Gly Glu Asn Pro Gln Arg Gln Gly Leu Leu Lys Thr Pro Trp
85 90 95
Arg Ala Ala Ser Ala Met Gln Phe Phe Thr Lys Gly Tyr Gln Glu Thr
100 105 110
Ile Ser Asp Val Leu Asn Asp Ala Ile Phe Asp Glu Asp His Asp Glu
115 120 125
Met Val Ile Val Lys Asp Ile Asp Met Phe Ser Met Cys Glu His His
130 135 140
Leu Val Pro Phe Val Gly Lys Val His Ile Gly Tyr Leu Pro Asn Lys
145 150 155 160
Gln Val Leu Gly Leu Ser Lys Leu Ala Arg Ile Val Glu Ile Tyr Ser
165 170 175
Arg Arg Leu Gln Val Gln Glu Arg Leu Thr Lys Gln Ile Ala Val Ala
180 185 190
Ile Thr Glu Ala Leu Arg Pro Ala Gly Val Gly Val Val Val Glu Ala
195 200 205
Thr His Met Cys Met Val Met Arg Gly Val Gln Lys Met Asn Ser Lys
210 215 220
Thr Val Thr Ser Thr Met Leu Gly Val Phe Arg Glu Asp Pro Lys Thr
225 230 235 240
Arg Glu Glu Phe Leu Thr Leu Ile Arg Ser
245 250
<210> 53
<211> 396
<212> PRT
<213> NP_001191.1 bone morphogenetic protein 2 preproprotein (BMP2) [Homo sapiens]
<400> 53
Met Val Ala Gly Thr Arg Cys Leu Leu Ala Leu Leu Leu Pro Gln Val
1 5 10 15
Leu Leu Gly Gly Ala Ala Gly Leu Val Pro Glu Leu Gly Arg Arg Lys
20 25 30
Phe Ala Ala Ala Ser Ser Gly Arg Pro Ser Ser Gln Pro Ser Asp Glu
35 40 45
Val Leu Ser Glu Phe Glu Leu Arg Leu Leu Ser Met Phe Gly Leu Lys
50 55 60
Gln Arg Pro Thr Pro Ser Arg Asp Ala Val Val Pro Pro Tyr Met Leu
65 70 75 80
Asp Leu Tyr Arg Arg His Ser Gly Gln Pro Gly Ser Pro Ala Pro Asp
85 90 95
His Arg Leu Glu Arg Ala Ala Ser Arg Ala Asn Thr Val Arg Ser Phe
100 105 110
His His Glu Glu Ser Leu Glu Glu Leu Pro Glu Thr Ser Gly Lys Thr
115 120 125
Thr Arg Arg Phe Phe Phe Asn Leu Ser Ser Ile Pro Thr Glu Glu Phe
130 135 140
Ile Thr Ser Ala Glu Leu Gln Val Phe Arg Glu Gln Met Gln Asp Ala
145 150 155 160
Leu Gly Asn Asn Ser Ser Phe His His Arg Ile Asn Ile Tyr Glu Ile
165 170 175
Ile Lys Pro Ala Thr Ala Asn Ser Lys Phe Pro Val Thr Arg Leu Leu
180 185 190
Asp Thr Arg Leu Val Asn Gln Asn Ala Ser Arg Trp Glu Ser Phe Asp
195 200 205
Val Thr Pro Ala Val Met Arg Trp Thr Ala Gln Gly His Ala Asn His
210 215 220
Gly Phe Val Val Glu Val Ala His Leu Glu Glu Lys Gln Gly Val Ser
225 230 235 240
Lys Arg His Val Arg Ile Ser Arg Ser Leu His Gln Asp Glu His Ser
245 250 255
Trp Ser Gln Ile Arg Pro Leu Leu Val Thr Phe Gly His Asp Gly Lys
260 265 270
Gly His Pro Leu His Lys Arg Glu Lys Arg Gln Ala Lys His Lys Gln
275 280 285
Arg Lys Arg Leu Lys Ser Ser Cys Lys Arg His Pro Leu Tyr Val Asp
290 295 300
Phe Ser Asp Val Gly Trp Asn Asp Trp Ile Val Ala Pro Pro Gly Tyr
305 310 315 320
His Ala Phe Tyr Cys His Gly Glu Cys Pro Phe Pro Leu Ala Asp His
325 330 335
Leu Asn Ser Thr Asn His Ala Ile Val Gln Thr Leu Val Asn Ser Val
340 345 350
Asn Ser Lys Ile Pro Lys Ala Cys Cys Val Pro Thr Glu Leu Ser Ala
355 360 365
Ile Ser Met Leu Tyr Leu Asp Glu Asn Glu Lys Val Val Leu Lys Asn
370 375 380
Tyr Gln Asp Met Val Val Glu Gly Cys Gly Cys Arg
385 390 395
<210> 54
<211> 272
<212> PRT
<213> NP_003947.1 cholesterol 25-hydroxylase (CH25H) [Homo sapiens]
<400> 54
Met Ser Cys His Asn Cys Ser Asp Pro Gln Val Leu Cys Ser Ser Gly
1 5 10 15
Gln Leu Phe Leu Gln Pro Leu Trp Asp His Leu Arg Ser Trp Glu Ala
20 25 30
Leu Leu Gln Ser Pro Phe Phe Pro Val Ile Phe Ser Ile Thr Thr Tyr
35 40 45
Val Gly Phe Cys Leu Pro Phe Val Val Leu Asp Ile Leu Cys Ser Trp
50 55 60
Val Pro Ala Leu Arg Arg Tyr Lys Ile His Pro Asp Phe Ser Pro Ser
65 70 75 80
Ala Gln Gln Leu Leu Pro Cys Leu Gly Gln Thr Leu Tyr Gln His Val
85 90 95
Met Phe Val Phe Pro Val Thr Leu Leu His Trp Ala Arg Ser Pro Ala
100 105 110
Leu Leu Pro His Glu Ala Pro Glu Leu Leu Leu Leu Leu His His Ile
115 120 125
Leu Phe Cys Leu Leu Leu Phe Asp Met Glu Phe Phe Val Trp His Leu
130 135 140
Leu His His Lys Val Pro Trp Leu Tyr Arg Thr Phe His Lys Val His
145 150 155 160
His Gln Asn Ser Ser Ser Phe Ala Leu Ala Thr Gln Tyr Met Ser Val
165 170 175
Trp Glu Leu Phe Ser Leu Gly Phe Phe Asp Met Met Asn Val Thr Leu
180 185 190
Leu Gly Cys His Pro Leu Thr Thr Leu Thr Phe His Val Val Asn Ile
195 200 205
Trp Leu Ser Val Glu Asp His Ser Gly Tyr Asn Phe Pro Trp Ser Thr
210 215 220
His Arg Leu Val Pro Phe Gly Trp Tyr Gly Gly Val Val His His Asp
225 230 235 240
Leu His His Ser His Phe Asn Cys Asn Phe Ala Pro Tyr Phe Thr His
245 250 255
Trp Asp Lys Ile Leu Gly Thr Leu Arg Thr Ala Ser Val Pro Ala Arg
260 265 270
<210> 55
<211> 159
<212> PRT
<213> AAH40592.1 TSLP protein [Homo sapiens]
<400> 55
Met Lys Cys Leu Gly Gln Ser Lys Lys Glu Glu Val Ser Phe Arg Lys
1 5 10 15
Ile Phe Ile Leu Gln Leu Val Gly Leu Val Leu Thr Tyr Asp Phe Thr
20 25 30
Asn Cys Asp Phe Glu Lys Ile Lys Ala Ala Tyr Leu Ser Thr Ile Ser
35 40 45
Lys Asp Leu Ile Thr Tyr Met Ser Gly Thr Lys Ser Thr Glu Phe Asn
50 55 60
Asn Thr Val Ser Cys Ser Asn Arg Pro His Cys Leu Thr Glu Ile Gln
65 70 75 80
Ser Leu Thr Phe Asn Pro Thr Ala Gly Cys Ala Ser Leu Ala Lys Glu
85 90 95
Met Phe Ala Met Lys Thr Lys Ala Ala Leu Ala Ile Trp Cys Pro Gly
100 105 110
Tyr Ser Glu Thr Gln Ile Asn Ala Thr Gln Ala Met Lys Lys Arg Arg
115 120 125
Lys Arg Lys Val Thr Thr Asn Lys Cys Leu Glu Gln Val Ser Gln Leu
130 135 140
Gln Gly Leu Trp Arg Arg Phe Asn Arg Pro Leu Leu Lys Gln Gln
145 150 155
<210> 56
<211> 472
<212> PRT
<213> NP_001538.4 IFIT2 [Homo sapiens]
<400> 56
Met Ser Glu Asn Asn Lys Asn Ser Leu Glu Ser Ser Leu Arg Gln Leu
1 5 10 15
Lys Cys His Phe Thr Trp Asn Leu Met Glu Gly Glu Asn Ser Leu Asp
20 25 30
Asp Phe Glu Asp Lys Val Phe Tyr Arg Thr Glu Phe Gln Asn Arg Glu
35 40 45
Phe Lys Ala Thr Met Cys Asn Leu Leu Ala Tyr Leu Lys His Leu Lys
50 55 60
Gly Gln Asn Glu Ala Ala Leu Glu Cys Leu Arg Lys Ala Glu Glu Leu
65 70 75 80
Ile Gln Gln Glu His Ala Asp Gln Ala Glu Ile Arg Ser Leu Val Thr
85 90 95
Trp Gly Asn Tyr Ala Trp Val Tyr Tyr His Met Gly Arg Leu Ser Asp
100 105 110
Val Gln Ile Tyr Val Asp Lys Val Lys His Val Cys Glu Lys Phe Ser
115 120 125
Ser Pro Tyr Arg Ile Glu Ser Pro Glu Leu Asp Cys Glu Glu Gly Trp
130 135 140
Thr Arg Leu Lys Cys Gly Gly Asn Gln Asn Glu Arg Ala Lys Val Cys
145 150 155 160
Phe Glu Lys Ala Leu Glu Lys Lys Pro Lys Asn Pro Glu Phe Thr Ser
165 170 175
Gly Leu Ala Ile Ala Ser Tyr Arg Leu Asp Asn Trp Pro Pro Ser Gln
180 185 190
Asn Ala Ile Asp Pro Leu Arg Gln Ala Ile Arg Leu Asn Pro Asp Asn
195 200 205
Gln Tyr Leu Lys Val Leu Leu Ala Leu Lys Leu His Lys Met Arg Glu
210 215 220
Glu Gly Glu Glu Glu Gly Glu Gly Glu Lys Leu Val Glu Glu Ala Leu
225 230 235 240
Glu Lys Ala Pro Gly Val Thr Asp Val Leu Arg Ser Ala Ala Lys Phe
245 250 255
Tyr Arg Arg Lys Asp Glu Pro Asp Lys Ala Ile Glu Leu Leu Lys Lys
260 265 270
Ala Leu Glu Tyr Ile Pro Asn Asn Ala Tyr Leu His Cys Gln Ile Gly
275 280 285
Cys Cys Tyr Arg Ala Lys Val Phe Gln Val Met Asn Leu Arg Glu Asn
290 295 300
Gly Met Tyr Gly Lys Arg Lys Leu Leu Glu Leu Ile Gly His Ala Val
305 310 315 320
Ala His Leu Lys Lys Ala Asp Glu Ala Asn Asp Asn Leu Phe Arg Val
325 330 335
Cys Ser Ile Leu Ala Ser Leu His Ala Leu Ala Asp Gln Tyr Glu Asp
340 345 350
Ala Glu Tyr Tyr Phe Gln Lys Glu Phe Ser Lys Glu Leu Thr Pro Val
355 360 365
Ala Lys Gln Leu Leu His Leu Arg Tyr Gly Asn Phe Gln Leu Tyr Gln
370 375 380
Met Lys Cys Glu Asp Lys Ala Ile His His Phe Ile Glu Gly Val Lys
385 390 395 400
Ile Asn Gln Lys Ser Arg Glu Lys Glu Lys Met Lys Asp Lys Leu Gln
405 410 415
Lys Ile Ala Lys Met Arg Leu Ser Lys Asn Gly Ala Asp Ser Glu Ala
420 425 430
Leu His Val Leu Ala Phe Leu Gln Glu Leu Asn Glu Lys Met Gln Gln
435 440 445
Ala Asp Glu Asp Ser Glu Arg Gly Leu Glu Ser Gly Ser Leu Ile Pro
450 455 460
Ser Ala Ser Ser Trp Asn Gly Glu
465 470
<210> 57
<211> 714
<212> PRT
<213> NP_055401.1 hormonally up-regulated neu tumor-associated kinase (HUNK) [Homo sapiens]
<400> 57
Met Pro Ala Ala Ala Gly Asp Gly Leu Leu Gly Glu Pro Ala Ala Pro
1 5 10 15
Gly Gly Gly Gly Gly Ala Glu Asp Ala Ala Arg Pro Ala Ala Ala Cys
20 25 30
Glu Gly Ser Phe Leu Pro Ala Trp Val Ser Gly Val Pro Arg Glu Arg
35 40 45
Leu Arg Asp Phe Gln His His Lys Arg Val Gly Asn Tyr Leu Ile Gly
50 55 60
Ser Arg Lys Leu Gly Glu Gly Ser Phe Ala Lys Val Arg Glu Gly Leu
65 70 75 80
His Val Leu Thr Gly Glu Lys Val Ala Ile Lys Val Ile Asp Lys Lys
85 90 95
Arg Ala Lys Lys Asp Thr Tyr Val Thr Lys Asn Leu Arg Arg Glu Gly
100 105 110
Gln Ile Gln Gln Met Ile Arg His Pro Asn Ile Thr Gln Leu Leu Asp
115 120 125
Ile Leu Glu Thr Glu Asn Ser Tyr Tyr Leu Val Met Glu Leu Cys Pro
130 135 140
Gly Gly Asn Leu Met His Lys Ile Tyr Glu Lys Lys Arg Leu Glu Glu
145 150 155 160
Ser Glu Ala Arg Arg Tyr Ile Arg Gln Leu Ile Ser Ala Val Glu His
165 170 175
Leu His Arg Ala Gly Val Val His Arg Asp Leu Lys Ile Glu Asn Leu
180 185 190
Leu Leu Asp Glu Asp Asn Asn Ile Lys Leu Ile Asp Phe Gly Leu Ser
195 200 205
Asn Cys Ala Gly Ile Leu Gly Tyr Ser Asp Pro Phe Ser Thr Gln Cys
210 215 220
Gly Ser Pro Ala Tyr Ala Ala Pro Glu Leu Leu Ala Arg Lys Lys Tyr
225 230 235 240
Gly Pro Lys Ile Asp Val Trp Ser Ile Gly Val Asn Met Tyr Ala Met
245 250 255
Leu Thr Gly Thr Leu Pro Phe Thr Val Glu Pro Phe Ser Leu Arg Ala
260 265 270
Leu Tyr Gln Lys Met Val Asp Lys Glu Met Asn Pro Leu Pro Thr Gln
275 280 285
Leu Ser Thr Gly Ala Ile Ser Phe Leu Arg Ser Leu Leu Glu Pro Asp
290 295 300
Pro Val Lys Arg Pro Asn Ile Gln Gln Ala Leu Ala Asn Arg Trp Leu
305 310 315 320
Asn Glu Asn Tyr Thr Gly Lys Val Pro Cys Asn Val Thr Tyr Pro Asn
325 330 335
Arg Ile Ser Leu Glu Asp Leu Ser Pro Ser Val Val Leu His Met Thr
340 345 350
Glu Lys Leu Gly Tyr Lys Asn Ser Asp Val Ile Asn Thr Val Leu Ser
355 360 365
Asn Arg Ala Cys His Ile Leu Ala Ile Tyr Phe Leu Leu Asn Lys Lys
370 375 380
Leu Glu Arg Tyr Leu Ser Gly Lys Ser Asp Ile Gln Asp Ser Leu Cys
385 390 395 400
Tyr Lys Thr Arg Leu Tyr Gln Ile Glu Lys Tyr Arg Ala Pro Lys Glu
405 410 415
Ser Tyr Glu Ala Ser Leu Asp Thr Trp Thr Arg Asp Leu Glu Phe His
420 425 430
Ala Val Gln Asp Lys Lys Pro Lys Glu Gln Glu Lys Arg Gly Asp Phe
435 440 445
Leu His Arg Pro Phe Ser Lys Lys Leu Asp Lys Asn Leu Pro Ser His
450 455 460
Lys Gln Pro Ser Gly Ser Leu Met Thr Gln Ile Gln Asn Thr Lys Ala
465 470 475 480
Leu Leu Lys Asp Arg Lys Ala Ser Lys Ser Ser Phe Pro Asp Lys Asp
485 490 495
Ser Phe Gly Cys Arg Asn Ile Phe Arg Lys Thr Ser Asp Ser Asn Cys
500 505 510
Val Ala Ser Ser Ser Met Glu Phe Ile Pro Val Pro Pro Pro Arg Thr
515 520 525
Pro Arg Ile Val Lys Lys Pro Glu Pro His Gln Pro Gly Pro Gly Ser
530 535 540
Thr Gly Ile Pro His Lys Glu Asp Pro Leu Met Leu Asp Met Val Arg
545 550 555 560
Ser Phe Glu Ser Val Asp Arg Asp Asp His Val Glu Val Leu Ser Pro
565 570 575
Ser His His Tyr Arg Ile Leu Asn Ser Pro Val Ser Leu Ala Arg Arg
580 585 590
Asn Ser Ser Glu Arg Thr Leu Ser Pro Gly Leu Pro Ser Gly Ser Met
595 600 605
Ser Pro Leu His Thr Pro Leu His Pro Thr Leu Val Ser Phe Ala His
610 615 620
Glu Asp Lys Asn Ser Pro Pro Lys Glu Glu Gly Leu Cys Cys Pro Pro
625 630 635 640
Pro Val Pro Ser Asn Gly Pro Met Gln Pro Leu Gly Ser Pro Asn Cys
645 650 655
Val Lys Ser Arg Gly Arg Phe Pro Met Met Gly Ile Gly Gln Met Leu
660 665 670
Arg Lys Arg His Gln Ser Leu Gln Pro Ser Ala Asp Arg Pro Leu Glu
675 680 685
Ala Ser Leu Pro Pro Leu Gln Pro Leu Ala Pro Val Asn Leu Ala Phe
690 695 700
Asp Met Ala Asp Gly Val Lys Thr Gln Cys
705 710
<210> 58
<211> 160
<212> PRT
<213> NP_056490.2 GADD45B [Homo sapiens]
<400> 58
Met Thr Leu Glu Glu Leu Val Ala Cys Asp Asn Ala Ala Gln Lys Met
1 5 10 15
Gln Thr Val Thr Ala Ala Val Glu Glu Leu Leu Val Ala Ala Gln Arg
20 25 30
Gln Asp Arg Leu Thr Val Gly Val Tyr Glu Ser Ala Lys Leu Met Asn
35 40 45
Val Asp Pro Asp Ser Val Val Leu Cys Leu Leu Ala Ile Asp Glu Glu
50 55 60
Glu Glu Asp Asp Ile Ala Leu Gln Ile His Phe Thr Leu Ile Gln Ser
65 70 75 80
Phe Cys Cys Asp Asn Asp Ile Asn Ile Val Arg Val Ser Gly Met Gln
85 90 95
Arg Leu Ala Gln Leu Leu Gly Glu Pro Ala Glu Thr Gln Gly Thr Thr
100 105 110
Glu Ala Arg Asp Leu His Cys Leu Leu Val Thr Asn Pro His Thr Asp
115 120 125
Ala Trp Lys Ser His Gly Leu Val Glu Val Ala Ser Tyr Cys Glu Glu
130 135 140
Ser Arg Gly Asn Asn Gln Trp Val Pro Tyr Ile Ser Leu Gln Glu Arg
145 150 155 160
<210> 59
<211> 480
<212> PRT
<213> AAH95399.1 Kruppel-like factor 10 (KLF10) [Homo sapiens]
<400> 59
Met Leu Asn Phe Gly Ala Ser Leu Gln Gln Thr Ala Glu Glu Arg Met
1 5 10 15
Glu Met Ile Ser Glu Arg Pro Lys Glu Ser Met Tyr Ser Trp Asn Lys
20 25 30
Thr Ala Glu Lys Ser Asp Phe Glu Ala Val Glu Ala Leu Met Ser Met
35 40 45
Ser Cys Ser Trp Lys Ser Asp Phe Lys Lys Tyr Val Glu Asn Arg Pro
50 55 60
Val Thr Pro Val Ser Asp Leu Ser Glu Glu Glu Asn Leu Leu Pro Gly
65 70 75 80
Thr Pro Asp Phe His Thr Ile Pro Ala Phe Cys Leu Thr Pro Pro Tyr
85 90 95
Ser Pro Ser Asp Phe Glu Pro Ser Gln Val Ser Asn Leu Met Ala Pro
100 105 110
Ala Pro Ser Thr Val His Phe Lys Ser Leu Ser Asp Thr Ala Lys Pro
115 120 125
His Ile Ala Ala Pro Phe Lys Glu Glu Glu Lys Ser Pro Val Ser Ala
130 135 140
Pro Lys Leu Pro Lys Ala Gln Ala Thr Ser Val Ile Arg His Thr Ala
145 150 155 160
Asp Ala Gln Leu Cys Asn His Gln Thr Cys Pro Met Lys Ala Ala Ser
165 170 175
Ile Leu Asn Tyr Gln Asn Asn Ser Phe Arg Arg Arg Thr His Leu Asn
180 185 190
Val Glu Ala Ala Arg Lys Asn Ile Pro Cys Ala Ala Val Ser Pro Asn
195 200 205
Arg Ser Lys Cys Glu Arg Asn Thr Val Ala Asp Val Asp Glu Lys Ala
210 215 220
Ser Ala Ala Leu Tyr Asp Phe Ser Val Pro Ser Ser Glu Thr Val Ile
225 230 235 240
Cys Arg Ser Gln Pro Ala Pro Val Ser Pro Gln Gln Lys Ser Val Leu
245 250 255
Val Ser Pro Pro Ala Val Ser Ala Gly Gly Val Pro Pro Met Pro Val
260 265 270
Ile Cys Gln Met Val Pro Leu Pro Ala Asn Asn Pro Val Val Thr Thr
275 280 285
Val Val Pro Ser Thr Pro Pro Ser Gln Pro Pro Ala Val Cys Pro Pro
290 295 300
Val Val Phe Met Gly Thr Gln Val Pro Lys Gly Ala Val Met Phe Val
305 310 315 320
Val Pro Gln Pro Val Val Gln Ser Ser Lys Pro Pro Val Val Ser Pro
325 330 335
Asn Gly Thr Arg Leu Ser Pro Ile Ala Pro Ala Pro Gly Phe Ser Pro
340 345 350
Ser Ala Ala Lys Val Thr Pro Gln Ile Asp Ser Ser Arg Ile Arg Ser
355 360 365
His Ile Cys Ser His Pro Gly Cys Gly Lys Thr Tyr Phe Lys Ser Ser
370 375 380
His Leu Lys Ala His Thr Arg Thr His Thr Gly Glu Lys Pro Phe Ser
385 390 395 400
Cys Ser Trp Lys Gly Cys Glu Arg Arg Phe Ala Arg Ser Asp Glu Leu
405 410 415
Ser Arg His Arg Arg Thr His Thr Gly Glu Lys Lys Phe Ala Cys Pro
420 425 430
Met Cys Asp Arg Arg Phe Met Arg Ser Asp His Leu Thr Lys His Ala
435 440 445
Arg Arg His Leu Ser Ala Lys Lys Leu Pro Asn Trp Gln Met Glu Val
450 455 460
Ser Lys Leu Asn Asp Ile Ala Leu Pro Pro Thr Pro Ala Pro Thr Gln
465 470 475 480
<210> 60
<211> 154
<212> PRT
<213> CAA54920.1 Id1 [Homo sapiens]
<400> 60
Met Lys Val Ala Ser Gly Ser Thr Ala Thr Ala Ala Ala Gly Pro Ser
1 5 10 15
Cys Ala Leu Lys Ala Gly Lys Thr Ala Ser Gly Ala Gly Glu Val Val
20 25 30
Arg Cys Leu Ser Glu Gln Ser Val Ala Ile Ser Arg Cys Arg Gly Ala
35 40 45
Gly Ala Arg Leu Pro Ala Leu Leu Asp Glu Gln Gln Val Asn Val Leu
50 55 60
Leu Tyr Asp Met Asn Gly Cys Tyr Ser Arg Leu Lys Glu Leu Val Pro
65 70 75 80
Thr Leu Pro Gln Asn Arg Lys Val Ser Lys Val Glu Ile Leu Gln His
85 90 95
Val Ile Asp Tyr Ile Arg Asp Leu Gln Leu Glu Leu Asn Ser Glu Ser
100 105 110
Glu Val Gly Thr Pro Gly Gly Arg Gly Leu Pro Val Arg Ala Pro Leu
115 120 125
Ser Thr Leu Asn Gly Glu Ile Ser Ala Leu Thr Ala Glu Ala Ala Cys
130 135 140
Val Pro Ala Asp Asp Arg Ile Leu Cys Arg
145 150
<210> 61
<211> 232
<212> PRT
<213> AAH34145.1 TM4SF1 protein [Homo sapiens]
<400> 61
Met Cys Tyr Gly Lys Cys Ala Arg Cys Ile Gly His Ser Leu Val Gly
1 5 10 15
Leu Ala Leu Leu Cys Ile Ala Ala Asn Ile Leu Leu Tyr Phe Pro Asn
20 25 30
Gly Glu Thr Lys Tyr Ala Ser Glu Asn His Leu Ser Arg Phe Val Trp
35 40 45
Phe Phe Ser Gly Ile Val Gly Gly Gly Leu Leu Met Leu Leu Pro Ala
50 55 60
Phe Val Phe Ile Gly Leu Glu Gln Asp Asp Cys Cys Gly Cys Cys Gly
65 70 75 80
His Glu Asn Cys Gly Lys Arg Cys Ala Met Leu Ser Ser Val Leu Ala
85 90 95
Ala Leu Ile Gly Ile Ala Gly Ser Gly Tyr Cys Val Ile Val Ala Ala
100 105 110
Leu Gly Leu Ala Glu Gly Pro Leu Cys Leu Asp Ser Leu Gly Gln Trp
115 120 125
Asn Tyr Thr Phe Ala Ser Thr Glu Gly Gln Tyr Leu Leu Asp Thr Ser
130 135 140
Thr Trp Ser Glu Cys Thr Glu Pro Lys His Ile Val Glu Trp Asn Val
145 150 155 160
Ser Leu Phe Ser Ile Leu Leu Ala Leu Gly Gly Ile Glu Phe Ile Leu
165 170 175
Cys Leu Ile Gln Val Ile Asn Gly Val Leu Gly Gly Ile Cys Gly Phe
180 185 190
Cys Cys Ser His Gln Gln Gln Met Thr Ala Lys Arg Thr Asn Pro Gly
195 200 205
Gln Ser His Asn Leu Pro Leu Phe His Cys Asn Leu Tyr Ile Ser Leu
210 215 220
Val Phe Ile Cys Lys Thr Leu Tyr
225 230
<210> 62
<211> 609
<212> PRT
<213> NP_001307488.1 cysteine/serine-rich nuclear protein 1 isoform a (CSRNP1) [Homo sapiens]
<400> 62
Met Ser Glu Thr Arg Leu Arg Leu Ser Val Pro Arg Pro Gln Ser Thr
1 5 10 15
Ser Gly Thr Thr Met Thr Gly Leu Leu Lys Arg Lys Phe Asp Gln Leu
20 25 30
Asp Glu Asp Asn Ser Ser Val Ser Ser Ser Ser Ser Ser Ser Gly Cys
35 40 45
Gln Ser Arg Ser Cys Ser Pro Ser Ser Ser Val Ser Arg Ala Trp Asp
50 55 60
Ser Glu Glu Glu Gly Pro Trp Asp Gln Met Pro Leu Pro Asp Arg Asp
65 70 75 80
Phe Cys Gly Pro Arg Ser Phe Thr Pro Leu Ser Ile Leu Lys Arg Ala
85 90 95
Arg Arg Glu Arg Pro Gly Arg Val Ala Phe Asp Gly Ile Thr Val Phe
100 105 110
Tyr Phe Pro Arg Cys Gln Gly Phe Thr Ser Val Pro Ser Arg Gly Gly
115 120 125
Cys Thr Leu Gly Met Ala Leu Arg His Ser Ala Cys Arg Arg Phe Ser
130 135 140
Leu Ala Glu Phe Ala Gln Glu Gln Ala Arg Ala Arg His Glu Lys Leu
145 150 155 160
Arg Gln Arg Leu Lys Glu Glu Lys Leu Glu Met Leu Gln Trp Lys Leu
165 170 175
Ser Ala Ala Gly Val Pro Gln Ala Glu Ala Gly Leu Pro Pro Val Val
180 185 190
Asp Ala Ile Asp Asp Ala Ser Val Glu Glu Asp Leu Ala Val Ala Val
195 200 205
Ala Gly Gly Arg Leu Glu Glu Val Ser Phe Leu Gln Pro Tyr Pro Ala
210 215 220
Arg Arg Arg Arg Ala Leu Leu Arg Ala Ser Gly Val Arg Arg Ile Asp
225 230 235 240
Arg Glu Glu Lys Arg Glu Leu Gln Ala Leu Arg Gln Ser Arg Glu Asp
245 250 255
Cys Gly Cys His Cys Asp Arg Ile Cys Asp Pro Glu Thr Cys Ser Cys
260 265 270
Ser Leu Ala Gly Ile Lys Cys Gln Met Asp His Thr Ala Phe Pro Cys
275 280 285
Gly Cys Cys Arg Glu Gly Cys Glu Asn Pro Met Gly Arg Val Glu Phe
290 295 300
Asn Gln Ala Arg Val Gln Thr His Phe Ile His Thr Leu Thr Arg Leu
305 310 315 320
Gln Leu Glu Gln Glu Ala Glu Ser Phe Arg Glu Leu Glu Ala Pro Ala
325 330 335
Gln Gly Ser Pro Pro Ser Pro Gly Glu Glu Ala Leu Val Pro Thr Phe
340 345 350
Pro Leu Ala Lys Pro Pro Met Asn Asn Glu Leu Gly Asp Asn Ser Cys
355 360 365
Ser Ser Asp Met Thr Asp Ser Ser Thr Ala Ser Ser Ser Ala Ser Gly
370 375 380
Thr Ser Glu Ala Pro Asp Cys Pro Thr His Pro Gly Leu Pro Gly Pro
385 390 395 400
Gly Phe Gln Pro Gly Val Asp Asp Asp Ser Leu Ala Arg Ile Leu Ser
405 410 415
Phe Ser Asp Ser Asp Phe Gly Gly Glu Glu Glu Glu Glu Glu Glu Gly
420 425 430
Ser Val Gly Asn Leu Asp Asn Leu Ser Cys Phe His Pro Ala Asp Ile
435 440 445
Phe Gly Thr Ser Asp Pro Gly Gly Leu Ala Ser Trp Thr His Ser Tyr
450 455 460
Ser Gly Cys Ser Phe Thr Ser Gly Val Leu Asp Glu Asn Ala Asn Leu
465 470 475 480
Asp Ala Ser Cys Phe Leu Asn Gly Gly Leu Glu Gly Ser Arg Glu Gly
485 490 495
Ser Leu Pro Gly Thr Ser Val Pro Pro Ser Met Asp Ala Gly Arg Ser
500 505 510
Ser Ser Val Asp Leu Ser Leu Ser Ser Cys Asp Ser Phe Glu Leu Leu
515 520 525
Gln Ala Leu Pro Asp Tyr Ser Leu Gly Pro His Tyr Thr Ser Gln Lys
530 535 540
Val Ser Asp Ser Leu Asp Asn Ile Glu Ala Pro His Phe Pro Leu Pro
545 550 555 560
Gly Leu Ser Pro Pro Gly Asp Ala Ser Ser Cys Phe Leu Glu Ser Leu
565 570 575
Met Gly Phe Ser Glu Pro Ala Ala Glu Ala Leu Asp Pro Phe Ile Asp
580 585 590
Ser Gln Phe Glu Asp Thr Val Pro Ala Ser Leu Met Glu Pro Val Pro
595 600 605
Val
Claims (8)
- PTX3(pentraxin 3), CXCL1(chemokine(C-X-C motif) ligand 1), CXCL2(chemokine(C-X-C motif) ligand 2), TNFAIP2(TNF alpha induced protein 2), IL8(interleukin 8), IL6(interleukin 6), NFKB1(nuclear factor of kappa light polypeptide gene enhancer in B-cells 1), G0S2(G0/G1 switch 2), ICAM(intercellular adhesion molecule), PTGES(prostaglandin E synthase), PMAIP1(phorbol-12-myristate-13-acetate-induced protein 1), SMOX(spermine oxidase), TNFAIP6(TNF alpha induced protein 6), MMP(matrix metallopeptidase 3), IFIT3(interferon induced protein with tetratricopeptide repeats 3), CXCL6(chemokine(C-X-C motif) ligand 6), BIRC3(baculoviral IAP repeat containing 3), BCL2A1(BCL2-related protein A1), GCH1(GTP cyclohydrolase 1), BMP2(bone morphogenetic protein 2), CH25H(cholesterol 25-hydroxylase), TSLP(thymic stromal lymphopoietin), IFIT2(interferon induced protein with tetratricopeptide repeats 2), HUNK(hormonally upregulated Neu-associated kinase), GADD45B(growth arrest and DNA damage inducible beta), KLF10(kruppel-like factor 10), ID1(inhibitor of DNA binding 1), TM4SF1(transmembrane 4 L six family member 1) 및 CSRNP1(cysteine-serine-rich nuclear protein 1) 유전자로 이루어진 군으로부터 선택되는 어느 하나 이상의 유전자의 mRNA 또는 상기 유전자가 코딩하는 단백질 수준을 측정하는 제제를 포함하는 치주염 진단용 조성물.
- 청구항 1에 있어서, 상기 유전자 중 GADD45B(growth arrest and DNA damage inducible beta), KLF10(kruppel-like factor 10), ID1(inhibitor of DNA binding 1), TM4SF1(transmembrane 4 L six family member 1) 및 CSRNP1(cysteine-serine-rich nuclear protein 1) 유전자로 이루어진 군으로부터 선택되는 어느 하나 이상의 유전자의 mRNA 또는 상기 유전자가 코딩하는 단백질 수준을 측정하는 제제를 포함하고, 상기 치주염은 노인성 치주염인, 조성물.
- 청구항 1 또는 2의 조성물을 포함하는 치주염 진단용 키트.
- 생물학적 시료에 존재하는 PTX3(pentraxin 3), CXCL1(chemokine(C-X-C motif) ligand 1), CXCL2(chemokine(C-X-C motif) ligand 2), TNFAIP2(TNF alpha induced protein 2), IL8(interleukin 8), IL6(interleukin 6), NFKB1(nuclear factor of kappa light polpeptide gene enhancer in B-cells 1), G0S2(G0/G1 switch 2), ICM1(intercellular adhesion molecule 1), ICM2(intercellular adhesion molecule 2), ICM3(intercellular adhesion molecule 3), PTGES(prostaglandin E synthase), PMAIP1(phorbol-12-myristate-13-acetate-induced protein 1), SMOX(spermine oxidase), TNFAIP6(TNF alpha induced protein 6), MMP(matrix metallopeptidase 3), IFIT3(interferon induced protein with tetratricopeptide repeats 3), CXCL6(chemokine(C-X-C motif) ligand 6), BIRC3(baculoviral IAP repeat containing 3), BCL2A1(BCL2-related protein A1), GCH1(GTP cyclohydrolase 1), BMP2(bone morphogenetic protein 2), CH25H(cholesterol 25-hydroxylase), TSLP(thymie stromal lymphopoietin), IFIT2(interferon induced protein with tetratricopeptide repeats 2), HUNK(hormonally upregulated Neu-associated kinase), GADD45B(growth arrest and DNA damage inducible beta), KLF10(kruppel-like factor 10), ID1(inhibitor of DNA binding 1), TM4SF1(transmembrane 4 L six family member 1) 및 CSRNP1(cysteine-serine-rich nuclear protein 1) 유전자로 이루어진 군으로부터 선택되는 어느 하나 이상의 유전자의 mRNA 또는 상기 유전자가 코딩하는 단백질의 발현 수준을 측정하는 단계; 및 상기 측정된 발현 수준을 정상 대조군의 발현 수준과 비교하는 단계를 포함하는, 치주염 진단을 위한 정보제공방법.
- 청구항 4에 있어서, 생물학적 시료에 존재하는 상기 유전자 중 GADD45B(growth arrest and DNA damage inducible beta), KLF10(kruppel-like factor 10), ID1(inhibitor of DNA binding 1), TM4SF1(transmembrane 4 L six family member 1) 및 CSRNP1(cysteine-serine-rich nuclear protein 1) 유전자로 이루어진 군으로부터 선택되는 어느 하나 이상의 유전자의 mRNA 또는 상기 유전자가 코딩하는 단백질의 발현 수준을 측정하는 단계; 및 상기 측정된 발현 수준을 정상 대조군의 발현 수준과 비교하는 단계를 포함하고, 상기 치주염은 노인성 치주염인, 방법.
- 청구항 4 또는 5에 있어서, 상기 생물학적 시료는 조직, 세포, 혈액, 혈청, 혈장, 타액 및 뇨로 이루어진 군으로부터 선택되는 것인, 방법.
- 개체 내 PTX3(pentraxin 3), CXCL1(chemokine(C-X-C motif) ligand 1), CXCL2(chemokine(C-X-C motif) ligand 2), TNFAIP2(TNF alpha induced protein 2), IL8(interleukin 8), IL6(interleukin 6), NFKB1(nuclear factor of kappa light polpeptide gene enhancer in B-cells 1), G0S2(G0/G1 switch 2), ICM1(intercellular adhesion molecule 1), ICM2(intercellular adhesion molecule 2), ICM3(intercellular adhesion molecule 3), PTGES(prostaglandin E synthase), PMAIP1(phorbol-12-myristate-13-acetate-induced protein 1), SMOX(spermine oxidase), TNFAIP6(TNF alpha induced protein 6), MMP(matrix metallopeptidase 3), IFIT3(interferon induced protein with tetratricopeptide repeats 3), CXCL6(chemokine(C-X-C motif) ligand 6), BIRC3(baculoviral IAP repeat containing 3), BCL2A1(BCL2-related protein A1), GCH1(GTP cyclohydrolase 1), BMP2(bone morphogenetic protein 2), CH25H(cholesterol 25-hydroxylase), TSLP(thymie stromal lymphopoietin), IFIT2(interferon induced protein with tetratricopeptide repeats 2), HUNK(hormonally upregulated Neu-associated kinase), GADD45B(growth arrest and DNA damage inducible beta), KLF10(kruppel-like factor 10), ID1(inhibitor of DNA binding 1), TM4SF1(transmembrane 4 L six family member 1) 및 CSRNP1(cysteine-serine-rich nuclear protein 1) 유전자로 이루어진 군으로부터 선택되는 어느 하나 이상의 유전자의 mRNA 또는 상기 유전자가 코딩하는 단백질의 발현 수준을 감소시키는 물질을 선별하는 단계를 포함하는 치주염 치료제의 스크리닝 방법.
- 청구항 7에 있어서, 개체 내 상기 유전자 중 GADD45B(growth arrest and DNA damage inducible beta), KLF10(kruppel-like factor 10), ID1(inhibitor of DNA binding 1), TM4SF1(transmembrane 4 L six family member 1) 및 CSRNP1(cysteine-serine-rich nuclear protein 1) 유전자로 이루어진 군으로부터 선택되는 어느 하나 이상의 유전자의 mRNA 또는 상기 유전자가 코딩하는 단백질의 발현 수준을 감소시키는 물질을 선별하는 단계를 포함하고, 상기 치주염은 노인성 치주염인, 방법.
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