KR20140057654A - Cmv용 백신으로서의 조건부 복제 시토메갈로바이러스 - Google Patents
Cmv용 백신으로서의 조건부 복제 시토메갈로바이러스 Download PDFInfo
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- KR20140057654A KR20140057654A KR1020147008959A KR20147008959A KR20140057654A KR 20140057654 A KR20140057654 A KR 20140057654A KR 1020147008959 A KR1020147008959 A KR 1020147008959A KR 20147008959 A KR20147008959 A KR 20147008959A KR 20140057654 A KR20140057654 A KR 20140057654A
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Abstract
본 발명은 조건부로 복제 결손인 유전자 변형된 시토메갈로바이러스 (CMV)를 사용하여 CMV에 대한 면역 반응을 유도하는 방법에 관한 것이다. 본 발명의 방법을 사용하여 1차 CMV 감염, 잠복성 CMV의 재활성화로 인한 감염, 및 이전에 접한 것과는 다른 CMV 균주에 의한 중복 감염을 치료 및/또는 예방할 수 있다. 본 발명은 또한 바이러스 복제가 외부에서 제어될 수 있게 하는 재조합적으로 변경된 복제 결손 CMV에 관한 것이다. 복제 결손 CMV를 포함하는 조성물이 또한 본 발명에 포함된다.
Description
본 발명은 조건부로 복제 결손인 유전자 변형된 시토메갈로바이러스 (CMV)를 사용하여 CMV에 대한 면역 반응을 유도하는 방법에 관한 것이다. 본 발명은 또한 바이러스 복제가 외부에서 제어될 수 있게 하는 재조합적으로 변경된 CMV에 관한 것이다. 복제 결손 CMV를 포함하는 조성물이 또한 본 발명에 포함된다.
인간 헤르페스바이러스 5 (HHV-5)로도 알려져 있는 시토메갈로바이러스 (CMV)는 헤르페스비리다애(herpesviridae)의 베타 서브패밀리의 구성원인 것으로 분류된 헤르페스바이러스이다. 미국 질병 통제 예방 센터(Centers for Disease Control and Prevention)에 따르면, CMV 감염은 인간 집단에 매우 편재하여 발견되며, 미국 성인 집단 중 40-80%가 감염된 것으로 추정된다. 바이러스는 주로 체액을 통해 확산되며, 빈번하게는 임산부에서 태아 또는 신생아에게로 전달된다. 대부분의 개체에서, 비록 바이러스 활성화를 통해 고열, 오한, 피로감, 두통, 오심, 및 비장 비대증이 유발되기는 하지만, CMV 감염은 잠복성을 띤다.
비록 대부분의 인간 CMV 감염은 무증상이지만, 면역력이 약화된 개체 (예컨대, HIV-양성 환자, 동종이계 이식 환자 및 암 환자) 또는 면역계가 아직 충분하게 발생 중인 사람 (예컨대, 신생아)에서의 CMV 감염은 특히 문제가 될 수 있다 (문헌 [Mocarski et al., Cytomegalovirus, in Field Virology, 2701-2772, Editor]: [Knipes and Howley, 2007]). 상기 개체에서 CMV 감염은 다른 유해한 병태 중에서도 폐렴, 간염, 뇌염, 결장염, 포도막염, 망막염, 실명, 및 신경병증을 포함하는, 중증의 병적 상태를 유발할 수 있다. 추가로, 임신 중의 CMV 감염은 선천적 결손증의 주된 원인이 된다 (문헌 [Adler, 2008 J. Clin Virol, 41 :231]; [Arvin et al., 2004 Clin Infect Dis, 39:233]; [Revello et al., 2008 J Med Virol, 80:1415]). CMV는 단핵구, 대식세포, 수지상 세포, 호중구, 내피 세포, 상피 세포, 섬유모세포, 뉴런, 평활근 세포, 간세포, 및 기질 세포를 포함하는, 생체내 다양한 세포를 감염시킨다 (문헌 [Plachter et al., 1996, Adv. Virus Res. 46:195]). 비록 임상 CMV 단리물은 다양한 세포 유형에서 복제되기는 하지만, 실험실용 균주 AD169 (문헌 [Elek & Stern, 1974, Lancet 1:1]) 및 타우니(Towne) (문헌 [Plotkin et al., 1975, Infect. Immun. 12:521])는 거의 배타적으로 섬유모세포에서만 복제된다 (문헌 [Hahn et al., 2004, J. Virol. 78:10023). 일련의 계대접종 및 섬유모세포에서의 바이러스의 최종의 적응으로 일어나는 굴성 제한이 약독화의 마커인 것으로 규정된다 (문헌 [Gerna et al., 2005, J. Gen. Virol. 86:275]; [Gerna et al., 2002, J. Gen Virol. 83: 1993]; [Gerna et al., 2003, J. Gen Virol. 84:1431]; [Dargan et al., 2010, J. Gen Virol. 91:1535]). 인간 CMV 실험실용 균주에서 상피 세포, 내피 세포, 백혈구, 및 수지상 세포 굴성을 손실시키는 돌연변이가 3개의 오픈 리핑 프레임 (ORF): UL128, UL130, 및 UL131로 지도화되었다 (문헌 [Hahn et al., 2004, J. Virol. 78:10023]; [Wang and Shenk, 2005 J. Virol. 79:10330]; [Wang and Shenk, 2005 Proc Natl Acad Sci USA. 102:18153]). 생화학적 및 재구성 연구를 통해 UL128, UL130 및 UL131은 gH/gL 스캐폴드 상에서 조립됨으로써 오량체 gH 복합체를 형성하는 것으로 나타났다 (문헌 [Wang and Shenk, 2005 Proc Natl Acad Sci USA. 102:1815]; [Ryckman et al., 2008 J. Virol. 82:60]). 비리온에서 상기 복합체를 복원하게 되면, 실험실용 균주에서 바이러스 상피 굴성은 복원된다 (문헌 [Wang and Shenk, 2005 J. Virol. 79:10330]).
내피 및 상피 굴성이 손실되어 있을 경우, 예컨대 타우니와 같은 백신으로서 이전에 평가받은 것에 결함이 있는 것으로 의심되었다 (문헌 [Gerna et al., 2002, J. Gen Virol. 83:1993]; [Gerna et al., 2003, J. Gen Virol. 84:1431]). 천연 CMV 감염의 인간 대상체로부터의 혈청 중 중화 항체는 섬유모세포 유입에 대한 것보다 바이러스 상피 유입에 대해 15배 초과로 더 높은 활성을 가진다 (문헌 [Cui et al., 2008 Vaccine 26:5760]). 1차 감염된 인간은 바이러스 내피 및 상피 유입에 대해 중화 항체를 빠르게 발생시키지만, 바이러스 섬유모세포 유입에 대한 중화 항체는 단지 서서히 발생시킨다 (문헌 [Gerna et al., 2008 J. Gen. Virol. 89:853]). 추가로, 바이러스 상피 및 내피 유입에 대한 중화 활성은 타우니 백신을 받은 인간 대상체로부터의 면역 혈청에는 존재하지 않는다 (문헌 [Cui et al., 2008 Vaccine 26:5760]). 더욱 최근에는, HCMV 감염된 4명의 기증자로부터의 인간 모노클로날 항체 패널이 기술된 바 있으며, 상기 패널로부터 유래된, 더욱 큰 효능을 가진 중화 클론이 오량체 gH 복합체의 항원을 인식하였다 (문헌 [Macagno et al., 2010 J. Virol. 84:1005]).
본 발명은 조건부 복제 결손 CMV (rdCMV), 및 조성물에서의 rdCMV의 용도, 및 환자에서 CMV에 의한 감염 또는 상기 감염과 연관된 병리를 치료하고/거나, 그의 가능성을 감소시키는 방법에 관한 것이다. 본원에 기술된 rdCMV는 탈안정화 단백질에 융합된 필수 단백질을 포함하는 하나 이상의 융합 단백질을 코딩하는 핵산을 포함한다. 안정화제의 부재하에서, 융합 단백질은 분해된다. 따라서, 복제가 허용되지만 (즉, 안정화제의 존재하에서), 환자에게 투여되었을 때에는 (즉, 안정화제의 부재하에서는) 복제가 감소되는, 바람직하게는 방해되는 조건하에 조직 배양물 중에서 rdCMV를 성장시킬 수 있다.
본 발명의 한 실시양태는 조건부 복제 결손 CMV이다. rdCMV는 탈안정화 단백질에 융합된 필수 단백질을 포함하는 하나 이상의 융합 단백질을 코딩하는 핵산을 포함한다. 야생형 필수 단백질을 코딩하는 핵산은 rdCMV에는 더 이상 존재하지 않으며, 따라서 바이러스 복제를 위해서는 융합 단백질이 요구된다. 바람직한 실시양태에서, 필수 단백질은 IE1/2, UL51, UL52, UL79 및 UL84로 이루어진 군으로부터 선택되고, 탈안정화 단백질은 FKBP 또는 그의 유도체이다.
본 발명의 또 다른 실시양태는 단리된 rdCMV 및 제약상 허용되는 담체를 포함하는 조성물이다. 조성물은 이스코매트릭스(ISCOMATRIX)® 아주반트 및 인산알루미늄 아주반트를 포함하나 이에 한정되지 않는 아주반트를 추가로 포함할 수 있다.
본 발명의 또 다른 실시양태는 환자에서 CMV에 대한 면역 반응을 유도하기 위한 rdCMV 조성물의 용도이다. 본 발명의 rdCMV를 투여함으로써 환자를 예방학적으로 또는 치료학적으로 치료할 수 있다. 예방학적 치료는 1차 감염, 재발성 감염 (즉, 잠복성 CMV의 재활성화로부터 유발된 것) 및 중복 감염 (즉, 환자가 이전에 경험한 것과는 다른 CMV 균주에 의한 감염으로부터 유발된 것)을 포함하는, CMV 감염의 가능성 또는 중증도를 감소시키는 데 충분한 방어 면역을 제공한다. 구체적인 실시양태에서, 가임 연령의 여성, 특히 청소년 전기의 여성을 백신접종하여 임신 중 CMV 감염 (1차, 재발성 또는 중복 감염)의 가능성을 감소시킴으로써, CMV가 태아로 전파될 가능성을 감소시킨다. 치료학적 치료를 수행함으로써 현 CMV 감염의 지속 기간/중증도를 단축/감소시킬 수 있다.
본 발명의 또 다른 실시양태는 쉴드(Shield)-1의 존재하에 상피 세포, 예컨대 ARPE-19 세포 (ATCC 수탁번호 CRL-2302) 상에서 rdCMV를 증식시키는 것을 포함하는, 본 발명의 rdCMV를 제조하는 방법이다. 일부 실시양태에서, rdCMV를 마이크로캐리어(microcarrier) 또는 고밀도 세포 배양 시스템 상의 상피 세포 상에서 증식시킨다.
도 1a-1b는 오량체 gH 복합체의 발현이 복원된 CMV 균주의 구축에 관한 개략적 다이어그램을 보여주는 것이다. (a) AD169 바이러스 게놈을 조작하기 위한 자가-절제가능한 박테리아 인공 염색체 (BAC) 생성 전략법. (b) 그의 발현을 복원시키기 위한 UL131 중 프레임 쉬프트 돌연변이 수복. (c) 자가-절제가능한 CMV BAC를 생성하기 위한 GFP의 cre 리콤비나제 유전자로의 대체.
도 2a-2d는 종래의 불활성화 방법이 gH 복합체 면역원성에 미치는 효과를 보여주는 것이다. γ-방사선 조사 (a, b) 및 β-프로피오락톤E (BPL) (c, d)를 사용하여 gH 복합체를 발현하는 CMV를 불활성화시켰다. 불활성화 동역학적 성질은 플라크 검정법으로 측정한 반면 (a, c), 면역원성은 CMV를 투여받은 마우스로부터의 혈청을 바이러스 상피 세포 유입에 대한 중화 활성에 대하여 평가함으로써 측정하였다 (b, d).
도 3은 FKBP 유도체에 융합된 다양한 필수 단백질과 함께, gH 복합체를 발현하는 CMV의 쉴드-1 농도에 의존적인 자손 바이러스 생산을 보여주는 것이다. ARPE-19 세포를 1 h 동안 0.01 PFU/세포의 다중도로 rdCMV 바이러스로 감염시키고, 새 배지로 2회에 걸쳐 세척하고, 0, 0.05, 0.1 0.5 또는 2 μM의 쉴드-1을 함유하는 성장 배지 중에서 인큐베이션시켰다. 감염 후 7일이 경과하였을 때, 무세포 바이러스를 수집하고, 2 μM의 쉴드-1의 존재하에 ARPE-19 세포 상에서 TCID50 검정법을 수행함으로써 바이러스 역가를 측정하였다.
도 4a-4d는 ARPE-19 세포에서의 rdCMV의 성장 동역학적 성질을 보여주는 것이다. 세포를 0.01 PFU/세포의 다중도로 (a) IE1/2, (b) UL51, (c) IE1/2-UL51 융합 단백질을 함유하는 바이러스, 또는 (d) 모 beMAD 바이러스로 감염시켰다. 1시간 후, 세포를 새 배지로 2회에 걸쳐 세척하고, 2 μM의 쉴드-1의 부재 (개방형 동그라미) 또는 존재 (폐쇄형 동그라미)하에서 인큐베이션시켰다. 감염 후 지정된 시점에 무세포 바이러스를 수집하고, 2 μM의 쉴드-1을 함유하는 배지 중 ARPE-19 세포에 대해 TCID50 검정법을 수행함으로써 감염성 바이러스를 정량화하였다.
도 5a-5e는 상이한 세포 유형에서의 IE1/2-UL51 rdCMV의 성장 동역학적 성질을 보여주는 것이다. (a) MRC-5 (b) HUVEC (c) AoSMC (d) SKMC (e) CCF-STTG1 세포를 rdCMV 바이러스로 감염시키고, 1시간 동안 인큐베이션시켰다. 세포를 새 배지로 2회에 걸쳐 세척한 후, 2 μM의 쉴드-1의 부재 (개방형 동그라미) 또는 존재 (폐쇄형 동그라미)하에서 인큐베이션시켰다. 감염 후 지정된 시점에 무세포 바이러스를 수집하고, 2 μM의 쉴드-1을 함유하는 배지 중 ARPE-19 세포에 대해 TCID50 검정법을 수행함으로써 감염성 바이러스를 정량화하였다.
도 6a-6c는 마우스, 토끼 및 레서스 마카크에서의 IE1/2-UL51 rdCMV의 면역원성 분석을 보여주는 것이다. (a) 마우스를 0 및 4주째에 beMAD (개방형 동그라미) 또는 IE1/2-UL51 rdCMV (폐쇄형 동그라미)로 면역화시켰다. (b) 토끼를 0, 3 및 8주째에 10 ㎍ beMAD 또는 지정된 rdCMV로 면역화시켰다. (c) 레서스 마카크를 0 및 8주째에 100 ㎍ beMAD 또는 IE1/2-UL51 rdCMV로 면역화시켰다. 각 경우에서, 혈청 샘플을 수집하고, CMV 미세-중화 검정법에 의해 ARPE-19 세포에 대하여 분석하였다. 선은 각 군에서의 중화의 기하 평균 역가 (NT50)를 나타낸다.
도 7은 이중 융합 바이러스 IE1/2-UL51로 백신접종된 레서스 마카크에서의 종방향 중화 역가를 보여주는 것이다. 레서스 원숭이 군 (n=5)을 (적색 삼각형으로 표시된 바와 같이) 0, 8, 및 24주째에 지정된 백신 용량 또는 제제로 백신접종하였고, 반면 한 군에는 0, 4 및 24주째에 gb/mf59 (30 mg/용량)를 투여하였다. 지정된 시점에 면역 혈청을 수집하고, 바이러스 중화 검정법으로 평가하였다. 각 군에 대한 NT50 역가의 GMT를 표준 오차와 함께 종방향으로 플롯팅하였다. AAHS: 비정질 알루미늄 히드록실포스페이트 술페이트; IMX: 이스코매트릭스; HNS: 염기 완충제.
도 8a-8d는 용량당 100 ㎍ (a) 또는 10 ㎍ (b-d)의 이중 융합 바이러스 IE1/2-UL51로 백신접종된 레서스 마카크에서의 IFN-γ ELISPOT를 보여주는 것이다. 아주반트 (a-b), AAHS (c) 또는 이스코매트릭스 (d)는 사용되지 않았다. HCMV 항원을 나타내는 펩티드 풀로 PBMC를 자극시켰다. 회색 막대는 군 (n=5)의 각 항원에 대한 GMT를 나타낸다. 각 항원에 대한 반응자 비율은 패널내 각 항원의 상단에 제시되어 있다.
도 9a-9b는 이중 융합 바이러스 IE1/2-UL51의 백신접종이 레서스 마카크에서 CD8+ (a) 및 CD4+ (b) 표현형 둘 모두의 T-세포 반응을 유도할 수 있다는 것을 보여주는 것이다. 아주반트로서의 이스코매트릭스®와 함께 100 ㎍ 또는 10 ㎍ 용량의 백신을 투여받은 원숭이로부터 PBMC를 수집하였다. HCMV 항원을 나타내는 펩티드 풀로 PBMC를 자극시킨 후, IFN-γ 및 CD4+/CD8+ 표면 T-세포 마커로 염색하였다. 데이터는 106개의 PBMC당 CD4+/CD8+ 양성, IFN-γ 양성인 세포의 개수로서 제시되었다. 선은 동일 백신을 받은 군 (n=5)의 기하 평균 (GMT)을 나타낸다. 그래프 하단에 기재된 수치는 백신접종된 두 군 모두 (n=10)의 GMT를 나타내는 것이다. CMV: 정제된 바이러스; SEB: 양성 대조군로서 사용된 미토겐; IMX: 이스코매트릭스.
도 10은 머크(Merck) 인산알루미늄 아주반트 (MAPA)가 원숭이에서 중화 항체 역가를 증진시킬 수 있다는 것을 보여주는 것이다. 레서스 원숭이를 0 및 8주째에 HNS (염기 완충제), AAHS 또는 MAPA 중에서 제제화된 30 ㎍ 용량의 이중 융합 바이러스 백신으로 면역화시켰다. 12주째에 혈청 샘플을 수집하고, 중화 역가에 대하여 평가하였다. 선은 각 군의 기하 평균을 나타낸다.
도 11a-11b는 상이한 온도하의 행크의 균형 염 용액 (HBSS) 중에서의 gH를 발현하는 CMV의 안정성을 보여주는 것이다. (a) HBSS 중 CMV 샘플을 4일 동안 지정된 온도에서 보관한 후, 바이러스 유입 검정법을 이용하여 CMV 바이러스 안정성을 평가하였다. (b) 바이러스 유입 검정 결과를 이용하여 샘플에 대한 EC50 값을 계산하였다. * 표시는 감염성을 완전히 상실함에 따라 EC50을 계산할 수 없다는 것을 나타낸다.
도 12a-12b는 실온에서 pH가 gH를 발현하는 CMV의 안정성에 미치는 효과를 보여주는 것이다. (a) 상이한 pH의 완충제 중 CMV 샘플을 실온에서 4일 동안 보관한 후, 바이러스 유입 검정법을 이용하여 CMV 바이러스 안정성을 측정하였다. (b) 바이러스 유입 검정 결과를 이용하여 샘플에 대한 EC50 값을 계산하였다.
도 13a-13b는 우레아 단독, 또는 염화나트륨과 조합된 우레아가 gH를 발현하는 CMV 바이러스 안정성에 미치는 효과를 보여주는 것이다. (a) 2% 우레아만 단독으로, 또는 150 mM NaCl과 함께 조합하여 실온에서 4일 동안 25 mM 히스티딘 완충제 (pH 6) 중의 CMV에 첨가한 후, 바이러스 유입 검정법을 이용하여 CMV 바이러스 안정성을 측정하였다. (b) 바이러스 유입 검정 결과를 이용하여 샘플에 대한 EC50 값을 계산하였다.
도 14a-14b는 이온 강도가 gH를 발현하는 CMV 바이러스 안정성에 미치는 효과를 보여주는 것이다. (a) 농도를 증가시키면서 NaCl (0 mM, 75 mM, 150 mM 및 320 mM NaCl)을 실온에서 4일 동안 25 mM 히스티딘 완충제 (pH 6) 중의 CMV에 첨가한 후, 바이러스 유입 검정법을 이용하여 CMV 바이러스 안정성을 측정하였다. (b) 바이러스 유입 검정 결과를 이용하여 샘플에 대한 EC50 값을 계산하였다.
도 15는 gH를 발현하는 CMV의 동결-해동 사이클에 대한 안정성에 대하여 동결보호제가 미치는 효과를 보여주는 것이다. 지정된 동결보호제를 25 mM 히스티딘 완충제 (pH 6) 중의 CMV에 첨가하고, 3회에 걸쳐 동결-해동 사이클을 수행한 후, 바이러스 유입 검정법을 이용하여 CMV 바이러스 안정성을 측정하였다. 바이러스 유입 검정 결과를 이용하여 샘플에 대한 EC50 값을 계산하였다.
도 16a-16b는 마우스 면역원성 연구에서 CMV 중화 항체를 유도하는 데 보관 온도가 미치는 효과를 보여주는 것이다. 마우스를 0일째 면역화시키고, 21일째 추가접종한 후, 28일째 출혈시켰다. ARPE-19 세포를 사용하여 gH를 발현하는 CMV에 대한 중화 항체에 대하여 마우스 혈청을 시험하였다. 비선형 곡선 피팅에 의해 NT50 역가를 수득하였다. (a) 면역원성 연구를 수행하기 전 3개월 동안 상이한 온도에서 CMV 샘플을 보관하였다. (b) 해동시킨 후, 면역원성 연구를 수행하기 전 8시간 동안 상이한 온도에서 CMV 샘플을 보관하였다.
도 2a-2d는 종래의 불활성화 방법이 gH 복합체 면역원성에 미치는 효과를 보여주는 것이다. γ-방사선 조사 (a, b) 및 β-프로피오락톤E (BPL) (c, d)를 사용하여 gH 복합체를 발현하는 CMV를 불활성화시켰다. 불활성화 동역학적 성질은 플라크 검정법으로 측정한 반면 (a, c), 면역원성은 CMV를 투여받은 마우스로부터의 혈청을 바이러스 상피 세포 유입에 대한 중화 활성에 대하여 평가함으로써 측정하였다 (b, d).
도 3은 FKBP 유도체에 융합된 다양한 필수 단백질과 함께, gH 복합체를 발현하는 CMV의 쉴드-1 농도에 의존적인 자손 바이러스 생산을 보여주는 것이다. ARPE-19 세포를 1 h 동안 0.01 PFU/세포의 다중도로 rdCMV 바이러스로 감염시키고, 새 배지로 2회에 걸쳐 세척하고, 0, 0.05, 0.1 0.5 또는 2 μM의 쉴드-1을 함유하는 성장 배지 중에서 인큐베이션시켰다. 감염 후 7일이 경과하였을 때, 무세포 바이러스를 수집하고, 2 μM의 쉴드-1의 존재하에 ARPE-19 세포 상에서 TCID50 검정법을 수행함으로써 바이러스 역가를 측정하였다.
도 4a-4d는 ARPE-19 세포에서의 rdCMV의 성장 동역학적 성질을 보여주는 것이다. 세포를 0.01 PFU/세포의 다중도로 (a) IE1/2, (b) UL51, (c) IE1/2-UL51 융합 단백질을 함유하는 바이러스, 또는 (d) 모 beMAD 바이러스로 감염시켰다. 1시간 후, 세포를 새 배지로 2회에 걸쳐 세척하고, 2 μM의 쉴드-1의 부재 (개방형 동그라미) 또는 존재 (폐쇄형 동그라미)하에서 인큐베이션시켰다. 감염 후 지정된 시점에 무세포 바이러스를 수집하고, 2 μM의 쉴드-1을 함유하는 배지 중 ARPE-19 세포에 대해 TCID50 검정법을 수행함으로써 감염성 바이러스를 정량화하였다.
도 5a-5e는 상이한 세포 유형에서의 IE1/2-UL51 rdCMV의 성장 동역학적 성질을 보여주는 것이다. (a) MRC-5 (b) HUVEC (c) AoSMC (d) SKMC (e) CCF-STTG1 세포를 rdCMV 바이러스로 감염시키고, 1시간 동안 인큐베이션시켰다. 세포를 새 배지로 2회에 걸쳐 세척한 후, 2 μM의 쉴드-1의 부재 (개방형 동그라미) 또는 존재 (폐쇄형 동그라미)하에서 인큐베이션시켰다. 감염 후 지정된 시점에 무세포 바이러스를 수집하고, 2 μM의 쉴드-1을 함유하는 배지 중 ARPE-19 세포에 대해 TCID50 검정법을 수행함으로써 감염성 바이러스를 정량화하였다.
도 6a-6c는 마우스, 토끼 및 레서스 마카크에서의 IE1/2-UL51 rdCMV의 면역원성 분석을 보여주는 것이다. (a) 마우스를 0 및 4주째에 beMAD (개방형 동그라미) 또는 IE1/2-UL51 rdCMV (폐쇄형 동그라미)로 면역화시켰다. (b) 토끼를 0, 3 및 8주째에 10 ㎍ beMAD 또는 지정된 rdCMV로 면역화시켰다. (c) 레서스 마카크를 0 및 8주째에 100 ㎍ beMAD 또는 IE1/2-UL51 rdCMV로 면역화시켰다. 각 경우에서, 혈청 샘플을 수집하고, CMV 미세-중화 검정법에 의해 ARPE-19 세포에 대하여 분석하였다. 선은 각 군에서의 중화의 기하 평균 역가 (NT50)를 나타낸다.
도 7은 이중 융합 바이러스 IE1/2-UL51로 백신접종된 레서스 마카크에서의 종방향 중화 역가를 보여주는 것이다. 레서스 원숭이 군 (n=5)을 (적색 삼각형으로 표시된 바와 같이) 0, 8, 및 24주째에 지정된 백신 용량 또는 제제로 백신접종하였고, 반면 한 군에는 0, 4 및 24주째에 gb/mf59 (30 mg/용량)를 투여하였다. 지정된 시점에 면역 혈청을 수집하고, 바이러스 중화 검정법으로 평가하였다. 각 군에 대한 NT50 역가의 GMT를 표준 오차와 함께 종방향으로 플롯팅하였다. AAHS: 비정질 알루미늄 히드록실포스페이트 술페이트; IMX: 이스코매트릭스; HNS: 염기 완충제.
도 8a-8d는 용량당 100 ㎍ (a) 또는 10 ㎍ (b-d)의 이중 융합 바이러스 IE1/2-UL51로 백신접종된 레서스 마카크에서의 IFN-γ ELISPOT를 보여주는 것이다. 아주반트 (a-b), AAHS (c) 또는 이스코매트릭스 (d)는 사용되지 않았다. HCMV 항원을 나타내는 펩티드 풀로 PBMC를 자극시켰다. 회색 막대는 군 (n=5)의 각 항원에 대한 GMT를 나타낸다. 각 항원에 대한 반응자 비율은 패널내 각 항원의 상단에 제시되어 있다.
도 9a-9b는 이중 융합 바이러스 IE1/2-UL51의 백신접종이 레서스 마카크에서 CD8+ (a) 및 CD4+ (b) 표현형 둘 모두의 T-세포 반응을 유도할 수 있다는 것을 보여주는 것이다. 아주반트로서의 이스코매트릭스®와 함께 100 ㎍ 또는 10 ㎍ 용량의 백신을 투여받은 원숭이로부터 PBMC를 수집하였다. HCMV 항원을 나타내는 펩티드 풀로 PBMC를 자극시킨 후, IFN-γ 및 CD4+/CD8+ 표면 T-세포 마커로 염색하였다. 데이터는 106개의 PBMC당 CD4+/CD8+ 양성, IFN-γ 양성인 세포의 개수로서 제시되었다. 선은 동일 백신을 받은 군 (n=5)의 기하 평균 (GMT)을 나타낸다. 그래프 하단에 기재된 수치는 백신접종된 두 군 모두 (n=10)의 GMT를 나타내는 것이다. CMV: 정제된 바이러스; SEB: 양성 대조군로서 사용된 미토겐; IMX: 이스코매트릭스.
도 10은 머크(Merck) 인산알루미늄 아주반트 (MAPA)가 원숭이에서 중화 항체 역가를 증진시킬 수 있다는 것을 보여주는 것이다. 레서스 원숭이를 0 및 8주째에 HNS (염기 완충제), AAHS 또는 MAPA 중에서 제제화된 30 ㎍ 용량의 이중 융합 바이러스 백신으로 면역화시켰다. 12주째에 혈청 샘플을 수집하고, 중화 역가에 대하여 평가하였다. 선은 각 군의 기하 평균을 나타낸다.
도 11a-11b는 상이한 온도하의 행크의 균형 염 용액 (HBSS) 중에서의 gH를 발현하는 CMV의 안정성을 보여주는 것이다. (a) HBSS 중 CMV 샘플을 4일 동안 지정된 온도에서 보관한 후, 바이러스 유입 검정법을 이용하여 CMV 바이러스 안정성을 평가하였다. (b) 바이러스 유입 검정 결과를 이용하여 샘플에 대한 EC50 값을 계산하였다. * 표시는 감염성을 완전히 상실함에 따라 EC50을 계산할 수 없다는 것을 나타낸다.
도 12a-12b는 실온에서 pH가 gH를 발현하는 CMV의 안정성에 미치는 효과를 보여주는 것이다. (a) 상이한 pH의 완충제 중 CMV 샘플을 실온에서 4일 동안 보관한 후, 바이러스 유입 검정법을 이용하여 CMV 바이러스 안정성을 측정하였다. (b) 바이러스 유입 검정 결과를 이용하여 샘플에 대한 EC50 값을 계산하였다.
도 13a-13b는 우레아 단독, 또는 염화나트륨과 조합된 우레아가 gH를 발현하는 CMV 바이러스 안정성에 미치는 효과를 보여주는 것이다. (a) 2% 우레아만 단독으로, 또는 150 mM NaCl과 함께 조합하여 실온에서 4일 동안 25 mM 히스티딘 완충제 (pH 6) 중의 CMV에 첨가한 후, 바이러스 유입 검정법을 이용하여 CMV 바이러스 안정성을 측정하였다. (b) 바이러스 유입 검정 결과를 이용하여 샘플에 대한 EC50 값을 계산하였다.
도 14a-14b는 이온 강도가 gH를 발현하는 CMV 바이러스 안정성에 미치는 효과를 보여주는 것이다. (a) 농도를 증가시키면서 NaCl (0 mM, 75 mM, 150 mM 및 320 mM NaCl)을 실온에서 4일 동안 25 mM 히스티딘 완충제 (pH 6) 중의 CMV에 첨가한 후, 바이러스 유입 검정법을 이용하여 CMV 바이러스 안정성을 측정하였다. (b) 바이러스 유입 검정 결과를 이용하여 샘플에 대한 EC50 값을 계산하였다.
도 15는 gH를 발현하는 CMV의 동결-해동 사이클에 대한 안정성에 대하여 동결보호제가 미치는 효과를 보여주는 것이다. 지정된 동결보호제를 25 mM 히스티딘 완충제 (pH 6) 중의 CMV에 첨가하고, 3회에 걸쳐 동결-해동 사이클을 수행한 후, 바이러스 유입 검정법을 이용하여 CMV 바이러스 안정성을 측정하였다. 바이러스 유입 검정 결과를 이용하여 샘플에 대한 EC50 값을 계산하였다.
도 16a-16b는 마우스 면역원성 연구에서 CMV 중화 항체를 유도하는 데 보관 온도가 미치는 효과를 보여주는 것이다. 마우스를 0일째 면역화시키고, 21일째 추가접종한 후, 28일째 출혈시켰다. ARPE-19 세포를 사용하여 gH를 발현하는 CMV에 대한 중화 항체에 대하여 마우스 혈청을 시험하였다. 비선형 곡선 피팅에 의해 NT50 역가를 수득하였다. (a) 면역원성 연구를 수행하기 전 3개월 동안 상이한 온도에서 CMV 샘플을 보관하였다. (b) 해동시킨 후, 면역원성 연구를 수행하기 전 8시간 동안 상이한 온도에서 CMV 샘플을 보관하였다.
본 발명은 조건부 복제 결손 CMV (rdCMV), 및 조성물에서의 rdCMV의 용도, 및 환자에서 CMV에 의한 감염 또는 상기 감염과 연관된 병리를 치료하고/거나, 그의 가능성을 감소시키는 방법에 관한 것이다. 본원에 기술된 rdCMV는 야생형 필수 단백질 대신 탈안정화 단백질에 융합된 필수 단백질을 포함하는 하나 이상의 융합 단백질을 코딩한다. 안정화제의 부재하에서, 융합 단백질은 숙주 세포 기구에 의해 분해된다. 안정화제의 존재하에서, 융합 단백질은 안정화되고, 분해되지 않는다.
본 발명에서 사용하기에 적합한 융합 단백질은 안정화제의 존재하에서는 숙주 세포에서의 바이러스 복제를 촉진시키고, 안정화제의 부재하에서는 CMV 복제를 감소 (바람직하게 50%, 75%, 90%, 95%, 또는 99% 초과로 감소)시키는 충분한 필수 단백질 활성을 보유한다. 바람직하게, 융합 단백질에서 사용하기 위한 필수 단백질은 비-구조 단백질을 코딩하고, 따라서 rdCMV 비리온으로 패키징되지 않는다. 본원에서 확인된 적합한 필수 단백질로는 필수 유전자 IE1/2, UL51, UL52, UL79 및 UL84에 의해 코딩되는 CMV 단백질을 포함한다.
탈안정화 단백질 및 안정화제의 예는 소형 분자를 사용하여 단백질의 안정성을 조절하기 위한 조성물, 시스템 및 방법을 개시하는 미국 특허 공개 번호 2009/0215169에 기술되어 있다. 간략하면, 안정성에 영향을 미치는 단백질, FKBP 또는 그의 유도체에 단백질을 융합시킨다. 외인성으로 첨가된, 세포 투과성 소형 분자인 쉴드-1 (Shld-1)은 FKBP 또는 그의 유도체와 상호작용하고, 융합 단백질을 안정화시킨다. 쉴드-1 부재하에서 FKBP 또는 그의 유도체는 융합 단백질이 숙주 세포 기구에 의해 분해되도록 지시한다.
본 발명의 실시양태에서, 필수 CMV 단백질은 FKBP 또는 그의 유도체에 융합된다. 쉴드-1 존재하에서 융합 단백질은 안정화된다. 그러나, 쉴드-1 부재하에서 FKBP 또는 그의 유도체는 융합 단백질이 숙주 세포 기구에 의해 분해되도록 지시한다.
융합 단백질의 부재하에서, rdCMV의 복제는 (바람직하게, 탈안정화된 필수 단백질을 포함하지 않는 CMV와 비교하여 50%, 75%, 90%. 95%, 또는 99% 초과만큼) 감소되거나, 방해된다.
본 발명의 방법에서 사용되는 재조합 바이러스는 또한 그의 비리온 상에 면역원성 오량체 gH 복합체를 나타낸다.
실시양태는 또한 본원에 기술된 재조합 CMV 또는 그의 조성물, 또는 (a) 요법 (예컨대, 인체용의 것); (b) 의약; (c) CMV 복제 억제; (d) CMV에 의한 감염 치료 또는 예방, 또는 (e) CMV 연관 질환(들) 치료, 예방, 또는 그의 발병 또는 진행 지연에서 (i) 사용하기 위한, (ii) 그를 위한 약제로서 사용하기 위한, 또는 (iii) 그를 위한 약제 제조에서 사용하기 위한 상기 CMV 또는 조성물을 포함하거나, 그로 이루어진 백신을 포함한다. 이러한 용도에서, 재조합 CMV, 그의 조합물, 및/또는 상기 CMV 또는 조성물을 포함하거나, 그로 이루어진 백신은 임의로 하나 이상의 항바이러스제 (예컨대, 하기 기술되는 항바이러스 화합물 또는 항바이러스 이뮤노글로불린; 조합 백신)와 조합하여 사용될 수 있다.
본원에서 사용되는 바, "면역 반응을 유도한다"라는 용어는 조건부 복제 결손 CMV를 투여받는 환자, 바람직하게 포유동물, 더욱 바람직하게 인간에서 면역 반응을 일으킬 수 있는 상기 CMV의 능력으로서, 여기서 상기 반응은 CMV에 특이적으로 결합하고, 바람직하게는 그를 중화시키고/거나, T 세포 활성화를 유발하는 요소 (예컨대, 항체) 생산을 포함하나 이에 한정되지 않는 것인 능력을 의미한다. "방어 면역 반응"은 환자가 CMV 감염 (1차, 재발성 및/또는 중복 감염 포함)과 접촉하게 될 가능성을 감소시키고/거나, 1개 이상의 CMV 감염과 연관된 병리를 호전시키고/거나, CMV 감염의 중증도/지속 기간을 감소/단축시키는 면역 반응이다.
본원에서 사용되는 바, "면역학상 유효량"이라는 용어는 환자에게 투여되었을 때, CMV에 대하여, 환자를 CMV 감염 (1차, 재발성 및/또는 중복 감염 포함)으로부터 방어할 수 있고/거나, 환자에서 1개 이상의 CMV 감염과 연관된 병리를 호전시키고/거나, CMV 감염의 중증도/지속 기간을 감소/단축시키는 면역 반응을 유도할 수 있는 면역원의 양을 의미한다. 상기 양은 CMV 감염의 가능성 또는 중증도를 유의적으로 감소시킬 수 있을 만큼 충분하여야 한다. 당업계에 공지된 동물 모델을 사용하여 면역원 투여의 방어 효과를 평가할 수 있다. 예를 들어, 면역원을 투여받은 개체로부터의 면역 혈청 또는 면역 T 세포는 항체 또는 세포독성 T 세포에 의해 중화 능력에 대하여, 또는 면역 T 세포에 의해 시토카인 생산 능력에 대하여 검정될 수 있다. 상기 평가를 위해 일반적으로 사용되는 검정법으로는 바이러스 중화 검정법, 항바이러스 항원 ELISA, 인터페론-감마 시토카인 ELISA, 인터페론-감마 ELISPOT, 세포내 다중-시토카인 염색 (ICS), 및 51크로뮴 방출 세포독성 검정법을 포함하나 이에 한정되지 않는다. 면역원의 면역학상 유효량을 측정하는 데에는 동물 시험 감염 모델 또한 사용될 수 있다.
본원에서 사용되는 바, "조건부 복제 결손 바이러스"라는 용어는 특정 환경에서는 복제가 가능하지만, 다른 환경에서는 복제가 불가능한 바이러스 입자를 의미한다. 바람직한 실시양태에서, 바이러스는 바이러스 복제에 필수적인 하나 이상의 단백질을 탈안정화시킴으로써 조건부 복제 결손 바이러스로 제조된다. 야생형인 비-탈안정화된 필수 단백질을 코딩하는 핵산은 조건부 복제 결손 바이러스에는 더 이상 존재하지 않는다. 탈안정화된 필수 단백질을 포함하지 않는 바이러스와 비교하여 하나 이상의 필수 단백질이 탈안정화되는 조건하에서 바이러스 복제는 바람직하게 50%, 75%, 90%. 95%, 99%, 또는 100% 초과만큼 감소된다. 그러나, 탈안정화된 필수 단백질을 안정화시키는 조건하에서 바이러스 복제는 바람직하게 탈안정화된 필수 단백질을 포함하지 않는 CMV의 복제량의 75%, 80%, 90%, 95%, 99% 또는 100% 이상으로 일어날 수 있다. 더욱 바람직한 실시양태에서, 하나 이상의 필수 단백질은 탈안정화 단백질, 예컨대 FKBP 또는 그의 유도체와의 융합에 의해 탈안정화된다. 상기 융합 단백질은 안정화제, 예컨대 쉴드-1의 존재에 의해 안정화될 수 있다. 본원에서 사용되는 바, "rdCMV"라는 용어는 조건부 복제 결손 시토메갈로바이러스를 의미한다.
바람직한 실시양태에서, 복제 결손 바이러스에 의해 유도되는 면역 반응은 그의 생(live) 바이러스 대응물과 비교하였을 때, 그 정도 및/또는 폭은 동일하거나, 실질적으로 유사하다. 다른 바람직한 실시양태에서, 전자 현미경법 분석에 의하면, 복제 결손 바이러스의 형태는 그의 생 바이러스 대응물과의 구별이 불가능하거나, 또는 그와 실질적으로 유사하다.
본원에서 사용되는 바, "FKBP"라는 용어는 서열 11의 탈안정화 단백질을 의미한다. FKBP를 포함하는 융합 단백질은 숙주 세포 기구에 의해 분해된다. 본원에서 사용되는 바, "FKBP 유도체"라는 용어는 하나 이상의 아미노산 치환, 결실 및/또는 부가에 의해 변경된 FKBP 단백질 또는 그의 일부를 의미한다. FKBP 유도체는 단백질에 융합되었을 때에는 FKBP의 탈안정화 특성을 실질적으로 모두 보유하고, 이는 또한 쉴드-1에 의해 안정화될 수 있는 FKBP의 능력을 실질적으로 모두 보유한다. 바람직한 FKBP 유도체는 언급된 아미노산 위치에서 하기 치환들 중 하나 이상을 가진다: F15S, V24A, H25R, F36V, E60G, M66T, R71G, D100G, D100N, E102G, K105I 및 L106P. F36V 및 L106P 치환을 갖는 FKBP 유도체 (서열 12)가 특히 바람직하다. 바람직한 실시양태에서, FKBP 또는 FKBP 유도체를 코딩하는 핵산은, 내인성 FKBP의 경우, 인간에서는 일반적으로 사용되지 않는 코돈을 적어도 일부 포함한다. 이를 통해 융합 단백질의 FKBP 또는 FKBP 유도체가 인간 게놈에서 그의 대응물과 재조합되거나 재배열될 가능성은 감소하게 된다. 서열 13의 핵산 서열은 상기 코돈을 사용하는 서열 12를 코딩한다.
본원에서 사용되는 바, "쉴드-1" 또는 "Shld1"라는 용어는 야생형 FKBP 및 그의 유도체에 결합하여 안정화제로서의 역할을 하는 합성 소형 분자를 의미한다. 야생형 FKBP와 비교하여 F36V 유도체에의 결합은 약 1,000배 더 밀착되어 이루어진다 (문헌 [Clackson et al., 1998, PNAS 95:10437-42]). 쉴드-1은 (본질적으로 문헌 [Holt et al., 1993, J. Am. Chem. Soc. 115:9925-38] 및 [Yang et al., 2000, J. Med. Chem. 43:1135-42] 및 [Grimley et al., 2008, Bioorganic & Medicinal Chemistry Letters 18:759]에 기술되어 있는 바와 같이) 합성될 수 있거나, 또는 케민파마 LLC(Cheminpharma LLC: 미국 코네티컷주 파밍턴) 또는 클론테크 라보라토리즈, 인크.(Clontech Laboratories, INC.: 미국 캘리포니아주 마운티 뷰)로부터 상업적으로 이용가능하다. 쉴드-1의 염 또한 본 발명의 방법에서 사용될 수 있다. 쉴드-1은 하기 구조식을 가진다:
본원에서 사용되는 바, "융합된" 또는 "융합 단백질"이라는 용어는 동일의 인접한 아미노산 서열의 일부로서 프레임 내에 배열된 2개의 폴리펩티드를 의미한다. 융합은 상기 폴리펩티드 사이에 어떤 추가적인 아미노산 잔기도 존재하지 않는 직접적인 융합일 수 있거나, 또는 성능을 개선시키거나 관능성을 부가하는 소형의 아미노산 링커가 존재하는 간접적인 융합일 수 있다. 바람직한 실시양태에서, 융합은 직접적인 융합이다.
본원에서 사용되는 바, "오량체 gH 복합체" 또는 "gH 복합체"라는 용어는 CMV 비리온 표면상의 5개의 바이러스 단백질로 이루어진 복합체를 의미한다. 복합체는 gH/gL 스캐폴드 상에서 조립된, UL128, UL130, 및 UL131에 의해 코딩된 단백질로 구성된다 (문헌 [Wang and Shenk, 2005 Proc Natl Acad Sci USA. 102:1815]; [Ryckman et al., 2008 J. Virol. 82:60]). CMV 균주 AD169로부터의 복합체 단백질의 서열은 진뱅크 수탁번호(GenBank Accession Nos.) NP_783797.1 (UL128), NP_040067 (UL130), CAA35294.1 (UL131), NP_040009 (gH, UL75로도 또한 알려져 있다) 및 NP 783793 (gL, UL115로도 또한 알려져 있다)에 제시되어 있다. 일부 약독화된 CMV 균주는 단백질이 발현되지 못하도록 UL131에 하나 이상의 돌연변이를 가지며, 이로써 gH 복합체는 형성되지 못한다. 상기 경우에서, gH 복합체가 본 발명의 rdCMV에서 발현되도록 하기 위해서는 UL131은 (예컨대, 문헌 [Wang and Shenk, 2005 J. Virol. 79:10330]에 기술되어 있는 것과 같은 방법을 사용하여) 수복되어야 한다. 본 발명의 바이러스는 오량체 gH 복합체를 구성하는 5개의 바이러스 단백질을 발현하고, 바이러스 외피 상에서 오량체 gH 복합체를 조립한다.
본원에서 사용되는 바, "필수 단백질"이라는 용어는 생체내 및 조직 배양물 중에서의 바이러스 복제에 필요한 바이러스 단백질을 의미한다. CMV에서의 필수 단백질의 예로는 IE1/2, UL37x1, UL44, UL51, UL52, UL53, UL56, UL77, UL79, UL84, UL87 및 UL105를 포함하나 이에 한정되지 않는다.
본원에서 사용되는 바, "탈안정화된 필수 단백질"라는 용어는 발현되어 바이러스 복제에서 그의 기능을 수행하고 안정화제의 부재하에서는 분해되는 필수 단백질을 의미한다. 바람직한 실시양태에서, 필수 단백질은 탈안정화 단백질, 예컨대 FKBP 또는 그의 유도체에 융합된다. 정상적인 성장 조건하에서는 (즉, 안정화제가 존재하지 않는 경우에는), 융합 단백질은 발현되지만, 숙주 세포 기구에 의해 분해된다. 분해로 인해 필수 단백질은 바이러스 복제에서 그 기능을 수행하지 못하게 되며, 따라서 필수 단백질의 기능은 녹아웃된다. 안정화제, 예컨대 쉴드-1이 존재하는 조건하에서, 융합 단백질은 안정화되고, 바람직하게는 탈안정화된 필수 단백질을 포함하지 않는 CMV의 복제량의 75%, 80%, 90%, 95%, 99% 또는 100% 이상으로 바이러스 복제를 지속시킬 수 있는 수준으로 그의 기능을 수행할 수 있다.
복제 결손
CMV
본 발명의 방법은 오량체 gH 복합체를 발현하는 복제 결손 CMV (rdCMV)를 사용한다. 오량체 gH 복합체를 발현하는 임의의 약독화된 CMV 바이러스는 본 발명의 방법에 따라 복제 결손화될 수 있다. 한 실시양태에서, 약독화된 CMV는 UL131 유전자 중의 돌연변이의 수복에 기인하여 gH 복합체 발현이 복원된 AD169이다 (실시예 1 참조).
조건부로 복제 결손인 바이러스는 하나 이상의 필수 바이러스 단백질이 필수 단백질의 탈안정화된 대응물에 의해 대체된 것인 돌연변이체이다. 탈안정화된 대응물은 필수 단백질과 탈안정화 단백질 사이의 융합 단백질을 코딩하는 핵산에 의해 코딩된다. 탈안정화된 필수 단백질은 오직 안정화제가 존재할 때에만 바이러스 복제를 지원하는 기능을 수행할 수 있다. 바람직한 실시양태에서, 미국 특허 공개 번호 2009/0215169에 기술된 방법을 사용하여 조건부로 복제 결손인 표현형을 오량체 gH 복합체를 발현하는 CMV에 부여한다. 간략하면, CMV 복제에 필수적인 하나 이상의 단백질을 탈안정화 단백질인 FKBP 또는 FKBP 유도체에 융합시킨다. 야생형 필수 단백질을 코딩하는 핵산은 rdCMV에 더 이상 존재하지 않는다. 외인성으로 첨가된, 세포 투과성 소형 분자 안정화제인 쉴드-1 (Shld-1)의 존재하에서, 융합 단백질은 안정화되고, 필수 단백질은 바이러스 복제를 지원하는 기능을 수행할 수 있다. 안정화제 존재하에서의 rdCMV의 복제는 바람직하게는 탈안정화 융합 단백질을 포함하지 않는 CMV (예컨대, rdCMV를 구축하는 데 사용되는 약독화된 모 CMV)의 복제량의 75%, 80%, 90%, 95%, 99% 또는 100% 이상이다. 쉴드-1의 부재하에서, 융합 단백질의 탈안정화 단백질은 융합 단백질이 숙주 세포 기구에 의해 실질적으로 분해되도록 지시한다. 필수 단백질이 전혀 존재하지 않거나 최소량으로 존재할 경우, CMV는 환자에서 CMV 감염을 일으키거나 유지할 수 있는 양으로 복제되지 못한다. 안정화제 부재하에서는 rdCMV의 복제가 일어날 수 없거나, 또는 탈안정화 융합 단백질을 포함하지 않는 CMV (예컨대, rdCMV를 구축하는 데 사용되는 약독화된 모 CMV)와 비교하여 바람직하게는 50%, 75%, 90%. 95%, 또는 99% 초과만큼 감소하게 된다.
당업계에 주지되어 있는 재조합 DNA 방법을 사용함으로써 CMV 복제 및/또는 CMV 감염의 확립/유지를 위한 필수 단백질을 코딩하는 핵산을, FKBP 또는 그의 유도체를 코딩하는 핵산에 부착시킨다. 코딩된 융합 단백질은 프레임 내에서 필수 단백질에 융합된 FKBP 또는 FKBP 유도체를 포함한다. 코딩된 융합 단백질은 쉴드-1의 존재하에서는 안정적이다. 그러나, 코딩된 융합 단백질은 쉴드-1의 부재하에서는 탈안정화되고, 파괴에 대해 표적화된다. 바람직한 실시양태에서, FKBP는 서열 11이다. 다른 바람직한 실시양태에서, FKBP 유도체는 F15S, V24A, H25R, F36V, E60G, M66T, R71G, D100G, D100N, E102G, K105I 및 L106P로 이루어진 군으로부터 선택된 하나 이상의 아미노산 치환을 포함하는 FKBP이다. 더욱 바람직한 실시양태에서, FKBP 유도체는 F36V 및/또는 L106P 치환을 포함한다 (서열 12). 더욱 바람직한 실시양태에서, FKBP 유도체는 서열 13에 의해 코딩된다.
FKBP 또는 그의 유도체와의 융합에 의한 탈안정화에 대해 표적화되는 필수 단백질은 1) 바이러스 복제에 필수적이고; 2) 필수 단백질의 기능을 실질적으로 파괴시키지 않으면서, 탈안정화 단백질의 융합을 수용할 수 있고; 3) 다른 주변 바이러스 유전자의 ORF를 실질적으로 파괴시키지 않으면서, 필수 단백질을 코딩하는 바이러스 ORF의 5' 또는 3' 말단에 FKBP 또는 그의 유도체를 코딩하는 핵산의 삽입을 수용할 수 있다. 바람직한 실시양태에서, FKBP 또는 그의 유도체와의 융합에 의한 탈안정화에 대해 표적화되는 필수 단백질은 비-구조 단백질을 코딩하고, 이로써 재조합 CMV 비리온으로 패키징될 가능성은 감소된다. 하기 표 1에는 상기 기준을 충족시키는 CMV 유전자가 제시되어 있다.
본 발명은 탈안정화 단백질에 융합된 필수 단백질 또는 그의 유도체를 포함하는 융합 단백질을 포함하는 rdCMV를 포함한다. 야생형 필수 단백질에 비하여 하나 이상의 아미노산 치환, 부가 및/또는 결실을 포함하는 필수 단백질 유도체는 쉴드-1의 존재하에서는 적어도 바이러스 복제를 지원할 수 있을 정도로 충분한 필수 단백질의 활성을 여전히 제공할 수 있다. 바이러스 활성 측정에 관한 예는 하기 실시예에서 제공한다. 당업계에 공지되어 있는 방법을 사용하여 관심 CMV 필수 단백질과 유도체 사이의 차이 정도를 측정할 수 있다. 한 실시양태에서, 서열 동일성을 사용하여 관계성을 측정할 수 있다. 본 발명의 유도체는 바람직하게는 기본 서열과 85% 이상 동일, 90% 이상 동일, 95% 이상 동일, 97% 이상 동일, 99% 이상 동일하다. 동일성 (%)은 동일한 잔기의 개수를 잔기 총 개수로 나누고, 거기에 100을 곱한 값으로 정의된다. 정렬된 서열의 길이가 (갭 또는 연장으로 인해) 상이할 경우, 가장 긴 서열의 길이를 전체 길이를 나타내는 값으로서 계산에 사용하게 될 것이다.
일부 실시양태에서, 탈안정화에 대해 표적화되는, 바이러스 복제에 필수적인 하나 이상의 바이러스 단백질은 IE1/2, UL51, UL52, UL84, UL79, UL87, UL37x1, UL77 및 UL53 또는 그의 유도체로 이루어진 군으로부터 선택된다. 구체적인 실시양태에서, 탈안정화에 대해 표적화되는, 바이러스 복제에 필수적인 하나 이상의 바이러스 단백질은 IE1/2, UL51, UL52, UL84, UL79, UL87로 이루어진 군으로부터 선택된다. 더욱 구체적인 실시양태에서, 탈안정화에 대해 표적화되는, 바이러스 복제에 필수적인 하나 이상의 바이러스 단백질은 IE1/2, UL51, UL52, UL79 및 UL84로 이루어진 군으로부터 선택된다.
FKBP 또는 그의 유도체에의 융합에 의해 1개 초과의 필수 단백질이 탈안정화될 수 있다. 일부 실시양태에서, 필수 단백질은 (극초기, 조기 또는 후기 단계를 포함하나 이에 한정되지 않는) CMV 복제 및/또는 감염의 상이한 단계에서 기능을 한다. 바람직한 실시양태에서, 탈안정화에 대해 표적화되는, 바이러스 복제에 필수적인 바이러스 단백질의 조합은 IE1/2와 UL51, IE1/2와 UL52, IE1/2와 UL79, IE1/2와 UL84, UL84와 UL51, 및 UL84와 UL52로 이루어진 군으로부터 선택된다. 더욱 바람직한 실시양태에서, IE1/2와 UL51은 같은 재조합 CMV에서 탈안정화에 대해 표적화된다. 가장 바람직한 실시양태에서, IE1/2을 포함하는 융합 단백질은 서열 1이고, UL51을 포함하는 융합 단백질은 서열 3이다. 서열 1 및 3은 각각 서열 2 및 4에 의해 코딩될 수 있다. 탈안정화된 IE1/2와 UL51을 포함하는 rdCMV의 게놈은 서열 14로 제시된다.
FKBP 또는 그의 유도체는 필수 단백질에 직접적으로 또는 간접적으로 융합될 수 있다. 바람직한 실시양태에서, FKBP 또는 그의 유도체는 필수 단백질에 직접적으로 융합된다.
FKBP 또는 그의 유도체는 필수 단백질의 N- 또는 C-말단에서 필수 단백질에 융합될 수 있다. 바람직한 실시양태에서, FKBP는 필수 단백질의 N-말단에 융합된다.
1개 초과의 FKBP 또는 그의 유도체가 필수 단백질에 융합될 수 있다. 1개 초과의 FKBP 또는 그의 유도체가 필수 단백질에 융합되는 실시양태에서, 각각의 개별 FKBP 또는 그의 유도체는 동일하거나, 상이할 수 있다. 바람직한 실시양태에서, 하나의 FKBP 또는 그의 유도체가 필수 단백질에 융합된다.
추가의 불활성화 방법
일부 실시양태에서, 상기 기술된 rdCMV는 추가로 화학적 또는 물리적 불활성화를 사용하여 불활성화된다. 그의 예로는 열 처리, 포름알데히드, β-프로피오락톤 (BPL), 또는 2원 에틸렌이민 (BEI)과의 인큐베이션, 또는 감마 방사선 조사를 포함한다. 바람직한 방법은 오량체 gH 복합체에 의해 유도되는 면역원성을 포함하나 이에 한정되지 않는 면역원성을 파괴시키지 않거나, 또는 실질적으로 파괴시키지 않는다. 따라서, 추가로 불활성화된 CMV에 의해 유도된 면역 반응은 추가의 불활성화 처리를 받지 않은 rdCMV와 비교하여 보존되거나, 실질적으로 보존된다. 바람직한 실시양태에서, 추가로 불활성화된 CMV의 중화 항체를 유도할 수 있는 능력은 추가의 불활성화 처리를 받지 않은 rdCMV에 의해 유도된 것과 유사하다. 화학적 또는 물리적 방법 중 어느 하나 또는 그의 조합에 의한 불활성화 요법은 오량체 gH 복합체를 포함하는 CMV의 면역원성을 보장할 수 있도록 실험적으로 결정된다.
바이러스 복제 평가
당업자는 FKBP 또는 그의 유도체에 융합된 특정 필수 단백질의 유용성을 측정하는 데 바이러스 복제 검정법을 사용할 수 있다. 유전자 발현/코딩된 생성물 기능이 쉴드-1의 존재하에서의 FKBP 또는 그의 유도체의 필수 단백질에의 부착에 의해 실질적으로는 영향을 받지 않아야 하기 때문에, rdCMV는 쉴드-1의 존재하에서 모 CMV와 유사한 비율로 (바람직하게 모 바이러스 수준의 75%, 80%, 90%, 95%, 99% 또는 100% 이상의 수준으로) 복제되어야 한다. rdCMV의 복제는 쉴드-1의 부재하에서는 모 CMV로부터 실질적으로 변경된다 (탈안정화 융합 단백질을 포함하지 않는 CMV와 비교하여 바람직하게 50%, 75%, 90%. 95%, 99% 또는 100% 초과만큼 감소된다).
바람직한 실시양태에서, 2 μM 이상의 쉴드-1의 존재하에서 rdCMV는 비-rdCMV의 복제량의 바람직하게 90% 이상, 더욱 바람직하게 95% 이상, 가장 바람직하게 99% 이상으로 복제된다.
한 실시양태에서, 2 μM 이상의 쉴드-1의 존재하에서 본 발명의 rdCMV를 포함하는 조성물의 바이러스 역가는 105 pfu/ml 이상, 더욱 바람직하게 107 pfu/ml 이상이다.
반대로, rdCMV는 실질적으로 쉴드-1의 부재하에서는 복제되지 않는다. 복제 결손 기전의 품질은 바이러스 복제를 허용하지 않는 조건하에서 제어가 얼마나 엄격하게 이루어지는지에 의해, 특히 상기 조건하에서 자손 비리온의 감염성 역가에 의해 판단된다. 본 발명의 rdCMV는 쉴드-1이 존재하지 않을 경우, (세포 배양물 중에서, 또는 환자 내에서) 실질적으로 복제불가능하다. ARPE-19 세포 및 다른 유형의 인간 1차 세포에서의 그의 복제는 조건부이고, 바이러스 복제를 지속시키기 위해서는 배양 배지 중 쉴드-1의 몰 농도는 0.1 μM 초과, 바람직하게는, 2 μM 이상이어야 한다.
한 실시양태에서, 쉴드-1의 부재하에서 본 발명의 rdCMV를 포함하는 조성물의 바이러스 역가는 2 pfu/ml 미만, 더욱 바람직하게 1 pfu/ml 미만이다.
CMV 복제를 평가하는 방법을 사용하여 쉴드-1의 존재 또는 부재하에서의 rdCMV 복제를 평가할 수 있다. 그러나, 바람직한 실시양태에서, TCID50이 사용된다.
또 다른 실시양태에서, rdCMV 역가는 50% 조직 배양 감염량 (TCID50) 검정법에 의해 측정된다. 간략하면, 본 희석 검정법은 감염된 숙주 중 50%를 사멸시키는 데 필요한 바이러스의 양을 정량화한다. 숙주 세포 (예컨대, ARPE-19 세포)를 플레이팅하고, 일련의 바이러스 희석액을 첨가한다. 인큐베이션시킨 후, 세포 사멸률 (즉, 세포 감염률) (%)을 관찰하고, 각 바이러스 희석액에 대하여 기록한다. 결과를 사용하여 TCID50을 수학적으로 계산한다.
또 다른 실시양태에서, rdCMV 역가는 플라크 검정법을 사용하여 측정된다. 바이러스 플라크 검정법은 바이러스 샘플 중 플라크 형성 단위 (pfu) 개수를 측정한다. 간략하면, 숙주 세포 (예컨대, ARPE-19 세포)의 융합성 단층을 다양한 희석률의 rdCMV로 감염시키고, 반고체 배지, 예컨대 아가 또는 카르복실메틸 셀룰로스를 커버링함으로써 바이러스 감염이 무차별적으로 확산되지 못하도록 막는다. 바이러스 플라크는 바이러스가 고정된 세포 단층 내의 세포를 감염시켰을 때에 형성된다. 바이러스로 감염된 세포는 용해되고, 감염을 인접한 세포로 확산시키며, 여기서 감염-대-용해 사이클이 반복된다. 감염된 세포 부위는 플라크 (비감염 세포 주변의 감염 부위)를 형성하게 될 것이며, 이는 육안으로, 또는 광학 현미경을 이용하여 관찰될 수 있다. 플라크를 계수하고, 결과는 플레이트를 제조하는 데 사용된 희석률과 조합하여 이용함으로써 샘플 단위 부피당 플라스 형성 단위 개수 (pfu/mL)를 계산한다. pfu/mL 결과는 샘플내 감염 입자의 개수를 나타내는 것이고, 형성된 각 플라크가 한 감염성 바이러스 입자를 나타낸다는 가정에 기초한다.
또 다른 실시양태에서, hu-SCID 마우스 모델을 사용하여 생체내에서 복제할 수 있는 rdCMV의 능력을 평가하였다. 간략하면, 인간 태아 조직 (예컨대, 흉선 및 간) 조각을 SCID 마우스의 신장 피막에 외과적으로 이식한다. 인간 조직에서 혈관화가 일어났을 때, 2-3개월 후에 rdCMV를 접종한다. 접종 후 3-4주 경과하였을 때, 플라크 검정법으로 바이러스 역가를 평가한다. 쉴드-1의 부재 또는 존재하에서 동물 실험을 수행할 수 있다.
면역 반응 평가
본 발명의 rdCMV를 환자에게 투여하면, 환자에서 CMV에 의한 감염 또는 상기 감염과 연관된 병리를 치료하고/거나, 그의 가능성을 감소시킬 수 있는, CMV에 대한 면역 반응, 바람직하게 방어 면역 반응이 유도된다. 면역 반응은 적어도 부분적으로는 오량체 gH 복합체에 대한 것이다.
rdCMV에 의해 유도되는 면역 반응은 당업계에 공지된 방법을 사용하여 평가할 수 있다.
당업계에 공지된 동물 모델을 사용하여 rdCMV 투여의 방어 효과를 평가할 수 있다. 한 실시양태에서, rdCMV를 투여받은 개체로부터의 면역 혈청을, 숙주 세포에의 바이러스 부착 또는 유입의 차단을 포함하나 이에 한정되지 않는 중화 능력에 대하여 검정할 수 있다. 다른 실시양태에서, rdCMV를 투여받은 개체로부터의 T 세포를 관심 항원의 존재하에서, 인터페론 감마를 포함하나 이에 한정되지 않는 시토카인 생산 능력에 대하여 검정할 수 있다. 또한, 동물 시험 감염 모델을 사용하여 면역원의 면역학상 유효량을 측정할 수 있다.
바이러스 중화란 바이러스 특이적 항체가 배양물 중에서 바이러스 유입 및/또는 복제를 차단시킬 수 있는 것을 의미한다. 중화 활성을 측정하는 일반 검정법은 바이러스 플라크 감소 검정법이다. 본 발명에서 중화 검정법은 세포로 유입되는 바이러스를 차단할 수 있는 혈청 적정을 의미한다. NT50 역가는 바이러스 중화 검정법에서 유입된 바이러스의 50%를 차단시킬 수 있는 혈청 희석률의 역수로서 정의된다. NT50 역가는 비선형 로지스틱 4-파라미터 곡선 피팅으로부터 수득된다.
복제 결손
CMV
의 측정
본 발명은 rdCMV를 제조하는 방법을 포함한다. 본 발명의 rdCMV는 안정화제, 예컨대 쉴드-1의 존재하에 상피 세포, 바람직하게 인간 상피 세포, 및 더욱 바람직하게 인간 망막 색소 상피 세포 상에서 증식된다. 추가의 실시양태에서, 인간 망막 색소 상피 세포는 아메리칸 타입 컬쳐 콜렉션(American Type Culture Collection: ATCC)에 수탁번호 CRL-2302로서 기탁된 ARPE-19 세포이다. 일부 실시양태에서, 쉴드-1은 조직 배양 배지 중에 0.5 μM 이상의 농도로 존재한다. 바람직한 실시양태에서, 쉴드-1은 조직 배양 배지에 중 2.0 μM 이상의 농도로 존재한다.
일부 실시양태에서, rdCMV를 증식시키는 데 사용되는 세포는 마이크로캐리어 상에서 성장시킨다. 마이크로캐리어는 스피너 플라스크 또는 바이오반응기 (예컨대, 회전벽 극미중력 생물반응기 및 유동상 생물반응기)에서 부착성 세포가 성장할 수 있도록 하는 지지체 매트릭스이다. 마이크로캐리어는 완만하게 교반시켰을 때, 현탁액 중에서 유지되도록 하는 밀도를 가진, 전형적으로 125 - 250 μM의 구체이다. 마이크로캐리어는 DEAE-덱스트란, 유리, 폴리스티렌 플라스틱, 아크릴아미드, 및 콜라겐을 포함하나 이에 한정되지 않는 다수의 상이한 물질로부터 제조될 수 있다. 마이크로캐리어는 세포외 기질 단백질, 재조합 단백질, 펩티드 및 하전된 분자를 포함하나 이에 한정되지 않는 상이한 표면의 화학 물질을 가질 수 있다. 다른 고밀도 세포 배양 시스템, 예컨대 코닝 하이퍼플라스크(Corning HyperFlask)® 및 하이퍼스택(HyperStack)® 시스템 또한 사용될 수 있다.
무세포 조직 배양 배지를 수집하고, rdCMV를 그로부터 정제할 수 있다. CMV 바이러스 입자의 직경은 약 200 nm이고, 이는 밀도 구배, 또는 20% 소르비톨 (Sorbitol) 쿠션을 통한 초원심분리를 포함하나 이에 한정되지 않는, 당업계에 공지된 기법을 사용하여 수거된 배지 중에 존재하는 다른 단백질로부터 분리될 수 있다. 백신의 단백질 질량은 브래드포드(Bradford) 검정법에 의해 측정될 수 있다.
쉴드-1은 FKBP와 함께 rdCMV의 복제를 제어하는 데 사용될 수 있다. 조직 배양 세포 중에서 원하는 양의 바이러스 증식이 완료되고 나면, 복제 능력은 더 이상 바람직하지 않다. (예컨대, 환자에게 투여될 수 있도록 하기 위한 목적으로) 바이러스가 복제 결핍이 되도록 하기 위해 쉴드-1은 rdCMV로부터 회수된다. 한 실시양태에서, rdCMV는 1회 이상의 세척으로 쉴드-1로부터 정제된다. 또 다른 실시양태에서, rdCMV는 초원심분리를 통해 쉴드-1로부터 정제된다. 또 다른 실시양태에서, rdCMV는 정용여과를 통해 쉴드-1로부터 정제된다. 정용여과는 바이러스 입자를 정제하는 데 일반적으로 사용된다. 한 실시양태에서, 공극 크기가 오직 쉴드-1만이 공극을 통해 통과할 수 있도록 하는 대략 750 킬로달톤인 필터가 사용된다.
쉴드-1로부터 rdCMV를 정제한 후, rdCMV 조성물에는 소량의 잔류 쉴드-1이 남아있을 수 있다. 한 실시양태에서, 정제 후, CMV 조성물 중 Shld-1의 수준은 조직 배양물 중에서의 복제를 지속시키는 필요한 수준보다 100배 이상 더 낮다. 또 다른 실시양태에서, 정제 후, rdCMV 조성물 중 쉴드-1의 수준은 0.1 μM 이하이다. 또 다른 실시양태에서, 정제 후, rdCMV 조성물 중 쉴드-1의 수준은 검출불가능한 수준이다.
조성물 중 쉴드-1의 수준 측정은 LC/MS (액체 크로마토그래피-질량 분광법) 또는 HPLC/MS (고성능 액체 크로마토그래피-질량 분광법) 검정법을 사용하여 검출될 수 있다. 이러한 기법은 LC 또는 HPLC의 물리적 분리 능력을, 복합체 혼합물 중의 관심 화학 물질을 검출할 수 있는 질량 분석 능력과 조합한 것이다.
아주반트
아주반트는 면역 반응을 일으키는 데 면역원을 도울 수 있는 물질이다. 아주반트는 상이한 기전에 의해, 예컨대 하기: 항원의 생물학적 또는 면역학적 반감기를 연장시키는 기전; 항원 제시 세포로의 항원 전달을 개선시키는 기전; 항원 제시 세포에 의한 항원 프로세싱 및 제시를 개선시키는 기전; 및 용량 절약을 달성하는 기전; 및 면역 조절 시토카인 생산을 유도하는 기전 중 하나 이상의 기전에 의해 기능을 할 수 있다 (문헌 [Vogel, 2000, Clin Infect Dis 30:S266]). 일부 실시양태에서, 본 발명의 조성물은 rdCMV 및 아주반트를 포함한다.
면역 반응 유발을 돕는 데 각종 상이한 유형의 아주반트가 사용될 수 있다. 특정 아주반트의 예로는 수산화알루미늄; 인산알루미늄, 수산화인산알루미늄, 비정질 알루미늄 히드록시포스페이트 술페이트 아주반트 (AAHSA) 또는 알루미늄의 다른 염; 인산칼슘; DNA CpG 모티프; 모노포스포릴 지질 A; 콜레라 독소; 이. 콜라이(E. coli) 이열성 독소; 백일해 독소; 무라밀 디펩티드; 프로인트 불완전 아주반트; MF59; SAF; 면역자극성 복합체; 리포솜; 생체분해성 미소구체; 사포닌; 비이온성 블록 공중합체; 무라밀 펩티드 유사체; 폴리포스파젠; 합성 폴리뉴클레오티드; IFN-γ; IL-2; IL-12; 및 ISCOMS를 포함한다 (문헌 [Vogel, 2000, Clin Infect Dis 30:S266]; [Klein et al., 2000, J Pharm Sci 89:311]; [Rimmelzwaan et al., 2001, Vaccine 19:1180]; [Kersten, 2003, Vaccine 21:915; O'Hagen, 2001, Curr. Drug Target Infect. Disord. 1:273.])
일부 실시양태에서, 불완전 프로인트 아주반트 및 MF59를 포함하나 이에 한정되지 않는 오일계 아주반트는 본 발명의 조성물에 사용되지 않는다.
다른 실시양태에서, 이스코매트릭스® 아주반트 및/또는 인산알루미늄 아주반트를 포함하나 이에 한정되지 않는 미립자 아주반트가 본 발명의 조성물에 사용된다.
제약 조성물
본 발명의 추가의 특징은 CMV 감염을 앓는 환자를 치료하기 위해 및/또는 CMV 감염의 가능성을 감소시키기 위해 조성물, 바람직하게 면역원성 조성물 또는 백신 중에, 본원에 기술된 재조합 CMV를 사용하는 것이다. 조성물이 제약상 허용되는 담체를 포함하는 것이 적합하다.
"제약상 허용되는 담체"란 전신 투여에 안전하게 사용될 수 있는 액체 충전제, 희석제 또는 캡슐화 물질을 의미하는 것으로 한다. 특정 투여 경로에 따라, 당업계에 주지되어 있는 다양한 제약상 허용되는 담체가 사용될 수 있다. 이러한 담체는 당, 전분, 셀룰로스 및 그의 유도체, 맥아, 젤라틴, 탈크, 황산칼슘, 식물성 오일, 합성 오일, 폴리올, 알긴산, 인산염 완충 염수를 포함하는 인산염 완충 용액, 유화제, 등장성 염수, 및 발열성 물질 무함유 물을 포함하는 군으로부터 선택될 수 있다. 특히, 제약상 허용되는 담체는 다른 성분, 예컨대 완충제, 멸균 주사용수, 생리 식염수 또는 인산염 완충 염수, 수크로스, 히스티딘, 염 및 폴리소르베이트를 포함할 수 있다. 예컨대, "생리학상 허용되는," "희석제" 또는 "부형제"라는 용어는 상호교환적으로 사용될 수 있다.
백신 제제에 대한 방법은 예를 들어, 문헌 [New Generation Vaccines (1997, Levine et al., Marcel Dekker, Inc. New York, Basel, Hong Kong)] (상기 문헌은 본원에 참조로 포함된다)에 개시되어 있다.
제제
일부 실시양태에서, 본 발명의 rdCMV는 면역 반응을 유도하기 위해 환자에게 투여된다. 면역원성 조성물을 보관하는 동안 rdCMV 조성물의 효능 손실을 최소화하거나, 또는 그를 막는 것이 바람직하다. 상기 목적을 지원하는 조건으로는 (1) 보관 중 안정성 유지, (2) 가해진 동결-해동 사이클에 대한 저항성, (3) 최대 1주 이상 동안 주변 온도에서 안정, (4) 면역원성 유지, (5) 아주반팅 전략법과의 상용성을 포함하나 이에 한정되지 않는다. rdCMV 안정성에 영향을 주는 조건으로는 완충제 pH, 완충제 이온 강도, 특정 부형제의 존재/부재 및 온도를 포함하나 이에 한정되지 않는다. 조성물은 백신 조성물로서 적합한 정제된 rdCMV 바이러스 입자의 안정성을 증가시키기 위하여 완충제를 포함한다.
마우스에서의 면역원성 검정법 및/또는 바이러스 유입 검정법에 의해 바이러스 입자의 무결성 보존을 평가할 수 있다. 바이러스 유입 사례는 오량체 gH 복합체를 포함하는 바이러스 당단백질의 무결성 및 기능에 의존한다. 오량체 gH 복합체는 또한 rdCMV의 실질적인 면역원성을 제공하며, 따라서 상기 2가지 특성은 연관되어 있다.
일부 실시양태에서, rdCMV를 pH 5 내지 7의, 15-35 mM 히스티딘 및 100-200 mM NaCl을 포함하는 완충제 중에 보관한다. 더욱 구체적인 실시양태에서, 완충제는 pH 6으로 25 mM 히스티딘과 150 mM NaCl을 포함한다.
다른 실시양태에서, 추가의 안정성을 제공하기 위해 당, 예컨대 폴리올 (만니톨 및 소르비톨을 포함하나 이에 한정되지 않는다); 모노사카라이드 (글루코스, 만노스, 갈락토스 및 프룩토스를 포함하나 이에 한정되지 않는다); 디사카라이드 (락토스, 말토스, 말토스, 수크로스, 락툴로스 및 트레할로스를 포함하나 이에 한정되지 않는다) 및 트리사카라이드 (라피노스 및 멜레지토스를 포함하나 이에 한정되지 않는다)가 첨가될 수 있다. 더욱 구체적인 실시양태에서, 당은 수크로스이다. 더욱더 구체적인 실시양태에서, 수크로스는 5-15%로 존재한다.
바람직한 실시양태에서, rdCMV는 pH 6의, 25 mM 히스티딘, 150 mM NaCl, 9% 수크로스를 포함하는 완충제 중에 보관된다.
투여
본원에 기술된 rdCMV는 당업계에 주지된 기법에 따라 본원에서 제공하는 지침을 사용하여 제제화되고, 환자에게 투여될 수 있다. 제약 투여를 위한 일반 가이드라인은 예를 들어, 문헌 [Vaccines Eds. Plotkin and Orenstein, W.B. Sanders Company, 1999]; [Remington's Pharmaceutical Sciences 20 th Edition , Ed. Gennaro, Mack Publishing, 2000]; 및 [Modern Pharmaceutics 2 nd Edition, Eds. Banker and Rhodes, Marcel Dekker, Inc., 1990]에 제공되어 있다.
백신은 상이한 경로, 예컨대 피하, 근육내, 정맥내, 점막, 비경구, 경피 또는 진피내로 투여될 수 있다. 피하 및 근육내 투여는 예를 들어, 니들 또는 제트 주사기를 사용함으로써 수행될 수 있다. 한 실시양태에서, 본 발명의 백신은 근육내로 투여된다. 경피 또는 진피내 전달은 진피내 시린지 니들 주사, 또는 기능성(enabling) 장치, 예컨대 마이크론-니들 또는 마이크론 어레치 패치를 통해 달성될 수 있다.
본원에 기술된 조성물은 투여 제형과 상용성인 방식으로, 및 CMV 감염 (1차, 재발성 및/또는 중복 감염 포함)을 치료하고/거나, 그의 가능성을 감소시키는 데 있어서 면역학상 효과적인 양으로 투여될 수 있다. 본 발명과 관련하여 환자에게 투여되는 용량은 시간이 경과함에 따라 환자에서 유익한 반응, 예컨대 CMV 감염 수준 감소, CMV 감염과 연관된 질환 증상의 호전 및/또는 CMV 감염의 지속 기간 및/또는 중증도의 단축/축소를 일으키는 데, 또는 CMV에 의한 감염 (1차, 재발성 및/또는 중복 감염 포함)의 가능성을 감소시키는 데 충분하여야 한다.
적합한 투여 요법은 당업자에 의해 쉽게 결정될 수 있으며, 바람직하게는 환자의 연령, 체중, 성별, 및 의학적 상태; 투여 경로; 원하는 효과; 및 사용되는 특정 조성물을 포함하는, 당업계에 주지되어 있는 인자들을 고려하여 결정된다. CMV에 대한 치료 또는 예방에서 rdCMV의 유효 투여량을 결정할 때, 의사는 바이러스의 순환 혈장 수준, 질환의 진행 상태, 및/또는 항-CMV 항체 생산을 평가할 수 있다. 백신 조성물의 용량은 103 내지 1012 플라크 형성 단위 (pfu) 범위로 구성된다. 상이한 실시양태에서, 투여량 범위는 104 내지 1010 pfu, 105 내지 109 pfu, 106 내지 108 pfu, 또는 상기 언급된 범위 내에 포함되는 임의의 용량이다. 1개 초과의 백신을 투여하고자 할 때 (즉, 조합 백신으로 투여하고자 할 때), 각 백신 제제의 양은 그의 기술된 범위 내에 포함되어 있는 양이다.
백신 조성물은 단일 투여 또는 다중 투여 형식으로 투여될 수 있다. 백신은 투여하기 수시간 또는 수일 전에 아주반트와 함께 제조될 수 있고, 안정화 완충제(들) 및 적합한 아주반트 조성물로 확인될 수 있다. 백신은 0.1 mL 내지 0.5 mL 범위의, 보통 실행되는 부피로 투여될 수 있다.
투여 시간은 당업계에 주지된 인자에 따라 달라진다. 초기 투여 후, 항체 역가 및 T 세포 면역을 유지 및/또는 증강시키기 위하여 1회 이상의 추가 용량을 투여할 수 있다. 부가적인 추가접종은 예컨대, ELISPOT와 같이, 항체 역가 및 T 세포 면역으로 반영되는 방어 면역 반응 수준을 지속시키는 데 필요할 수 있다. 상기 면역 반응의 수준이 임상 조사의 대상이 된다.
조합 백신을 위해, 각 면역원을 하나의 조성물로 함께, 또는 상이한 조성물로 별개로 투여할 수 있다. 본원에 기술된 rdCMV는 하나 이상의 원하는 면역원과 함께 동시에 투여된다. "동시에"라는 용어는 정확하게 동일한 시간에 치료제를 투여하는 것으로 제한되는 것이 아니라, 그보다는 본원에 기술된 rdCMV 및 다른 원하는 면역원(들)을 그들이 함께 작용함으로써 다르게 투여된 경우보다 증가된 이점을 제공할 수 있도록 하는 순서로 및 시간 간격 내에 대상체에게 투여하는 것을 의미한다. 예를 들어, 각 치료제는 동시에 또는 시간상 다른 시점에 임의의 순서로 순차적으로 투여될 수 있다; 그러나, 동시에 투여되지 않을 경우에는 상기 치료제가 원하는 치료학적 효과를 제공할 수 있도록 시간상 충분히 가까운 시점에 투여되어야 한다. 각 치료제는 별개로, 임의의 적절한 형태로, 및 임의의 적합한 경로에 의해 투여될 수 있다.
환자 집단
"환자"란 CMV로 감염될 수 있는 포유동물을 의미한다. 바람직한 실시양태에서, 환자는 인간이다. 환자는 예방학상 또는 치료학상 치료받을 수 있다. 예방학적 치료는 1차 감염, 재발성 감염 (즉, 잠복성 CMV의 재활성화로부터 유발된 것) 및 중복 감염 (즉, 환자가 이전에 경험한 것과는 다른 CMV 균주에 의한 감염으로부터 유발된 것)을 포함하는, CMV 감염의 가능성 또는 중증도를 감소시키는 데 충분한 방어 면역을 제공한다. 치료학적 치료를 수행함으로써 CMV 감염의 중증도를 감소시킬 수 있고, 재발성 또는 중복 감염의 가능성/중증도를 감소시킬 수 있다.
본원에 기술된 바와 같이 rdCMV를 포함하는 제약 조성물을 사용하여 치료를 수행할 수 있다. 제약 조성물은 일반 집단에게, 특히 CMV 감염 (1차, 재발성 또는 중복 감염)의 위험이 증가되어 있는 사람에게, 또는 CMV 감염이 특별히 문제가 될 수 있는 사람 (예컨대, 면역력이 약화된 개체, 이식 환자 또는 임산부)에게 투여할 수 있다. 한 실시양태에서, 가임 연령의 여성, 특히 청소년 전기의 여성을 백신접종하여 임신 중 CMV 감염 (1차, 재발성 또는 중복 감염)의 가능성을 감소시킨다.
치료를 필요로 하는 대상체는 이미 감염된 대상체 뿐만 아니라, 쉽게 감염될 수 있는 대상체, 또는 감염 가능성을 축소시키고 싶어하는 대상체를 포함한다. 치료를 통해, 잠복성 CMV의 재활성화로 인한 감염을 포함하는, CMV 감염과 연관된 질환의 증상을 호전시킬 수 있고/거나, CMV 감염의 지속 기간 및/또는 중증도를 단축 (또는 축소)시킬 수 있다.
CMV 감염 (1차, 재발성 또는 중복 감염)의 위험이 증가되어 있는 사람으로는 면역력이 약화된 환자 또는 면역력 약화를 유도하는 요법을 받고 있는 (예컨대, 암 화학요법 또는 방사선 요법을 받고 있거나, 또는 면역억제 약물을 복용하고 있는) 환자를 포함한다. 본원에서 사용되는 바, "면역력이 약화된"이라는 것은 면역 반응이 적절하게 작용하지 못하거나, 정상적인 건강한 성인 수준으로 작용하지 못하기 때문에, 감염과 싸울 수 있는 면역계의 능력이 저하된 것을 의미한다. 면역력이 약화된 환자의 예로는 영아, 유아, 노인, 임산부인 환자, 또는 면역계의 기능에서 병을 유발하는 질환, 예컨대 HIV 감염 또는 AIDS 환자가 있다.
실시예
하기 실시예는 본 발명의 상이한 특징들을 추가로 설명하기 위해 제공되는 것이다. 본 실시예는 또한 본 발명을 수행하는 데 유용한 방법을 예시한다. 본 실시예는 본 청구 발명을 제한하지 않는다.
실시예
1:
오량체
gH
복합체의 복원
코딩된 비리온이 gH/gL 스캐폴드 상에서 조립된, UL128, UL130 및 UL131로 구성된 오량체 gH 복합체를 발현하도록 감염성 CMV 박테리아 인공 염색체 클론을 구축하였다.
CMV 균주 AD169 균주는 원래 7세 여아의 아데노이드로부터 단리되었다 (문헌 [Elek and Stern, 1974, Lancet, 1:1]). 바이러스를 약독화시키기 위하여 바이러스를 여러 가지 유형의 인간 섬유모세포에서 58회에 걸쳐 계대접종하였고 (문헌 [Neff et al., 1979, Proc Soc Exp Biol Med, 160:32]), 마지막 5회는 WI-38 인간 섬유모세포에서 계대접종하였다. 본 연구에서 머크 AD169 (MAD169)로 지칭되는, AD169 바이러스의 상기 계대접종된 변이체를 감염성 BAC 클론 구축을 위한 모 바이러스로서 사용하였다. 모 바이러스 AD169도 계대접종된 변이체 바이러스 MAD169도 UL131 또는 오량체 gH 복합체를 발현하지 못했다.
MAD169를 감염성 박테리아 인공 염색체 (BAC) 클론을 구축하기 위한 모 바이러스로서 사용하였다. BAC 벡터는 이. 콜라이에서 크기가 큰 DNA 단편, 예컨대 CMV 게놈 (~230 Kb)의 유전자 조작을 가능케 하는 분자 도구이다. GFP 마커 유전자와 함께 BAC 요소를, 상기 단편의 양쪽 단부 모두에 생성된 LoxP 부위와 함께 (바이러스 게놈 중 US28과 US29 ORF 사이인) US28 오픈 리딩 프레임의의 종결 코돈 바로 뒤에 삽입하였다 (도 1a). 간략하면, 두 loxP 부위 및 CMV US28-US29 서열이 측면에 위치하는, GFP 발현 카세트를 함유하는 DNA 단편을 합성하고, pBeloBAC11 벡터로 클로닝하였다. BAC 벡터를 제한 효소 Pme I로 선형화하고, 정제된 비리온으로부터 추출된 MAD169 DNA와 함께 MRC-5 세포 내로 공형질감염시켰다. 녹색 형광 발현에 의해 확인되는 재조합 변이체를 플라크 정제하였다. 1회 증폭 후, 감염된 세포로부터 환형 형태의 바이러스 게놈을 추출하고, 이. 콜라이 DH10 세포 내로 전기천공시켰다. PCR을 수행하여 박테리아 콜로니를 US28 및 US29 영역의 존재에 대하여 스크리닝하였다. EcoR I, EcoR V, Hind III, Spe I 및 Bam HI 제한 분석에 의해 후보 클론을 추가로 조사하였다. 스크리닝 후, 한 클론, 즉, bMAD-GFP는 모 MAD169 바이러스와 동일한 제한 패턴을 보였다.
MAD169에서 상피 굴성 결핍의 근간이 되는 UL131의 제1 엑손에서의 프레임 쉬프트 돌연변이를 이. 콜라이에서 유전적으로 수복시켰다 (도 1b). 구체적으로, UL131 유전자에서 7 뉴클레오티드 (nt)의 A-스트레치로부터 1 아데닌 nt를 결실시켰다 (도 1b). UL131에 기인하는 상피 및 내피 세포 굴성을 구제하는 데에는 1 nt의 결실이면 충분하였고, 이로써, 오량체 gH 복합체가 발현되었다. 발현은 ELISA 및 웨스턴 블롯에 의해 확인하였다 (데이터를 나타내지 않음). LoxP/Cre 재조합에 의해 BAC 세그먼트를 제거시킴으로써 상기 클론을 추가로 변형시켰다. ARPE-19 세포인 인간 망막 색소 상피 세포 (ATCC 수탁번호 CRL-2302)에서 BAC DNA를 형질감염시켜 감염성 바이러스를 회복시켰다 (도 1c). BAC 유래 상피 굴성 MAD169 바이러스 (beMAD)로 명명되는 생성된 감염성 바이러스는 단 2개의 유전자좌, (1) 단일 아데닌 뉴클레오티드가 결실된 UL131 ORF, 및 (2) US28과 US29 ORF 사이에 삽입된 34 bp LoxP 부위에서만 MAD169와 차이를 보인다 (표 2 참조).
BAC 클론 beMAD의 게놈의 서열을 완전히 분석하였다. beMAD의 전체적인 게놈 구조는, 2개의 고유 영역, 고유 장쇄 (UL) 및 고유 단쇄(US)로 구성된, ATCC AD169 변이체 (진뱅크 수탁번호 X17403)에서 보고된 것과 동일하다. 각 고유 영역은 2개의 반복 서열인 말단 반복 장쇄 (TRL)-내부 반복 장쇄 (IRL), 말단 반복 단쇄 (TRS)-내부 반복 단쇄 (IRS)로 나뉜다. MRC-5 세포인 인간 섬유모세포 세포주 (ATCC 수탁번호 CCL-171)에서 계대접종된 변이체인 MAD169 및 beMAD 유래 바이러스의 성장 동역학적 성질은 구별이 불가능하였다 (데이터를 나타내지 않음). 섬유모세포 세포에서의 성장을 위해서는 gH 복합체가 요구되지 않기 때문에, MAD169와 beMAD 사이의 gH 복합체 발현상의 차이는 관련이 없었다.
실시예
2:
종래의 불활성화 방법이
gH
복합체에 미치는 효과
바이러스를 불활성화시키는 종래의 두가지 방법인 γ-방사선 조사 및 β-프로피오락톤 (BPL)이 gH를 발현하는 CMV에 미치는 효과에 대하여 조사하였다.
동결 건조된 비리온에 대하여 γ-방사선 조사를 수행하였다. 보존적 동결 건조 사이클 (-50℃에서 동결 및 -35℃에서 ~30 hrs 동안 1차 건조 후, 25℃에서 6 hrs 동안 2차 건조)을 사용하여 HNS (25 mM 히스티딘, 150 mM NaCl, 9% w/v 수크로스 (pH 6.0)) 제제 중 0.15 mg/mL 농도의 재조합 CMV 백신을 동결 건조시킴으로써 건조 분말을 수득하였다. 각 바이알에 0.5 ml 충전된 3 mL의 유리 바이알 중에서 백신을 동결 건조시켰다. 동결 건조 종결시, 질소 환경하에서 마개로 바이알을 막고, 샘플을 제거하고, 표지화하고, 크림핑시키고, 감마 방사선 조사시까지 -70℃에서 보관하였다. 원하는 조사량 만큼의 방사선 조사를 수행하기 위해 Co 방사선 조사기하에서 바이알에 방사선 조사하였다.
BPL 처리를 위해, ARPE-19 세포 상에서의 성장으로부터의 조 바이러스 배양 상청액에 BPL 원액을 첨가하여 최종 농도가 0.01% 또는 0.1% (v/v)에 도달하도록 하였다. 다양한 시점에서 티오황산나트륨으로 반응을 종결시켰다. 이어서, BPL로 처리된, gH를 발현하는 CMV를 초원심분리에 의해 정제하였다.
ARPE-19 세포에서 플라크 검정법에 의해 상기 두 방법 모두에 대한 불활성화 동역학적 성질을 측정하였다. 간략하면, PBS 중의 일련의 바이러스 샘플 희석액을 제조하고, ARPE-19 세포가 시딩된 6-웰 플레이트의 각 웰에 접종하는 데 상기 희석액 0.1 mL를 사용하였다. 플레이트를 37℃에서 1 hr 동안 인큐베이션시킨 후, 0.5% 아가로스를 함유하는 웰 중첩 배지당 6 mL씩을 첨가하였다. 플레이트를 37℃에서 18일 동안 인큐베이션시켰다. 플라크를 시각화하기 위해, 5 mg/mL의 약 0.5 mL MTT 용액 (티아졸릴 블루 세트라졸륨 브로마이드, 시그마(Sigma) M5655)을 각 웰에 첨가하였다. 플레이트를 37℃에서 2-4 hr 동안 인큐베이션시키고, 플라크를 라이트박스하에서 계수하였다 (도 2a 및 2c).
마우스에서 유도된 중화 항체 역가를 측정함으로써 불활성화된, gH를 발현하는 CMV의 면역원성을 검정하였다. 간략하면, 0 및 3주째 암컷 Balb/c 마우스 (n=10)를 용량당 2.5 ㎍의 CMV로 면역화시켰다. 4주째 혈청을 수집하고, 바이러스 상피 유입에 대한 중화 활성을 평가하였다. 중화 역가 (NT50)는 음성 대조군과 비교하여 바이러스 상피 유입을 50% 감소시키는 혈청 희석률의 역수로서 정의하였다. 마우스 면역원성 연구 결과, 종래의 불활성화 방법 두가지 모두 gH를 발현하는 CMV에 의해 유도된 중화 항체 역가에 대하여 부정적인 영향을 미치는 것으로 나타났다 (도 2b 및 2d). NT50 역가 감소는 γ-방사선 조사 또는 BPL에 의한 처리 지속 기간과 상관 관계가 있었다. 장시간 동안 처리할 경우, 오량체 gH 복합체를 발현하는 CMV는 마우스의 면역원성면에서 모 AD169 CMV와 더욱 유사해졌다. γ-방사선 조사 또는 BPL로 불활성화된 백신을 테스트하였을 때, 토끼 및 레서스 원숭이에서 유사한 결과가 관찰되었다 (데이터를 나타내지 않음). 이러한 관찰 결과는 오량체 gH 복합체가 선택된 불활성화 조건하에서 상기 두 불활성화 방법 모두에 대해 감응성이라는 것을 나타내는 것이었다.
실시예
3:
FKBP
-필수 단백질
융합물
구축 및 스크리닝
약독화된 AD169 균주 골격을 사용하여, 조건부로 복제 결손이면서 그의 상피 굴성을 보유하는 CMV를 구축하였다. 실시예 1에 기술된 방법을 사용하여 상피 굴성을 복원시켰다.
2가지 기준에 기초하여 FKBP 유도체에 융합시키고자 하는 바이러스 단백질을 선택하였다. 첫째, 프로테오믹스 분석에 의해 CMV 비리온에서는 관심 단백질이 검출되지 않았고 (문헌 [Varnum et al., 2004, J. Virol. 78:10960]), 따라서 FKBP 융합 단백질이 바이러스 내로 도입될 가능성을 감소시켰다. 둘째, 관심 단백질은 조직 배양물 중에서의 바이러스 복제에 필수적이다.
모 바이러스로서 beMAD를 사용하여 FKBP 유도체 (서열 12)를 IE1/2 (서열 1), pUL37x1, pUL44, pUL51 (서열 3), pUL52 (서열 5), pUL53, pUL56, pUL77, pUL79 (서열 7), pUL84 (서열 9), pUL87 및 pUL105를 포함하는, 12개의 필수 바이러스 단백질에 개별적으로 융합시켰다. 각각의 IE1/2 및 UL51이 FKBP 유도체에 융합된, 상이한 두 필수 단백질이 FKBP에 융합된 바이러스 또한 구축하였다 (탈안정화된 IE1/2와 UL51을 포함하는 rdCMV의 게놈은 서열 14에 제시되어 있다). 구축 후, 재조합 BAC DNA 모두를 ARPE-19 세포에 형질감염시키고, Shld-1을 함유하는 배지 중에서 배양하였다.
Shld-1에 대한 바이러스 성장의 의존성을 조사하였다. 플라크 검정법에서 IE1/2, UL51, UL52, UL84, UL79 및 UL87 융합 바이러스는 2 μM Shld-1에서 쉽게 구제되었다 (데이터를 나타내지 않음). UL37x1, UL77 및 UL53 바이러스 또한 플라크를 생성하지만, 플라크는 작았고, 모 beMAD와 비교하여 유의적으로 더 느리게 성장하였다. Shld-1 농도를 10 μM로 증가시켰을 때, 바이러스 성장이 유의적으로 촉진되지는 않았다 (데이터를 나타내지 않음). UL56 및 UL105 융합물은 회복되지 않았는데, 이는 상기 단백질의 태그부착이 상기 단백질의 기능, 또는 이웃 유전자의 발현을 파괴시킨다는 것을 제안한다.
다양한 농도의 Shld-1을 추가 실험에서 사용하여 Shld-1의 존재 또는 부재하에서의 바이러스 복제를 추가로 평가하였다. 필수 단백질에 융합된 FKBP 유도체 또한 포함하는, gH를 발현하는 CMV에 의해 ARPE-19 세포를 0.01 pfu/ml의 MOI로 감염시켰다. 1시간 동안 감염시킨 후, 세포를 새 배지로 2회에 걸쳐 세척하여 접종물로부터 Shld-1을 제거하였다. 이어서, 0.05, 0.1, 0.5 또는 2 μM의 쉴드-1을 함유하는 배지에서 배양된 ARPE-19 세포에 접종물을 첨가하였다. 감염 후 7일 경과하였을 때, 상청액 중 무세포 자손 바이러스를 수집하고, 2 mM의 쉴드-1로 보충된 ARPE-19 세포에서 적정하였다. 50% 조직 배양 감염량 (TCID50) 검정법에 의해 바이러스 역가를 측정하였다. 간략하면, 상기 희석 검정법을 통해 감염된 숙주 중 50%를 사멸시키는 데 필요한 바이러스의 양을 정량화하였다. ARPE-19 세포를 플레이팅하고, 일련의 바이러스 희석액을 첨가하였다. 인큐베이션 후, 세포 사멸률 (즉, 세포 감염률) (%)을 수동으로 관찰하고, 각 바이러스 희석액에 대하여 기록하였다. 결과를 사용하여 TCID50을 수학적으로 계산하였다.
도 3에 제시되어 있는 바와 같이, 비록 그 정도는 다르기는 하지만, 모든 FKBP 융합물을 함유하는 CMV의 효율적인 복제는 쉴드-1 농도에 의존하였다. 저농도의 쉴드-1은 일반적으로 자손 바이러스 생산의 역가를 감소시켰다. 단일 융합을 포함하는 바이러스 중에서, 오직 UL51 및 UL52만이 절대적으로 복제를 위해서 쉴드-1을 필요로 하였다. 단일 융합물 IE1/2, UL84, UL79, 및 UL87을 포함하는 다른 바이러스는 쉴드-1의 부재하에서 검출가능한 자손 바이러스를 생산할 수 있었다. FKBP 유도체가 UL51 또는 UL52에 융합되었을 때 가장 엄격하게 조절되었다.
IE1/2, UL51, IE1/2-UL51 융합물을 포함하는 바이러스의 성장 동역학적 성질을 2 μM의 Shld-1의 존재 또는 부재하에서 모 beMAD 바이러스와 비교하였다. 도 4에 제시되어 있는 바와 같이, Shld-1의 존재하에서는 단일 또는 이중 융합물의 성장 동역학적 성질은 모 beMAD와 유사하였다. 그러나, Shld-1의 부재하에서는, 비록 모 beMAD보다는 더 낮고, 속도가 더 느리기는 하였지만, 오직 IE1/2만이 복제가능하였다.
상이한 세포 유형에서 이중 융합 바이러스에서의 바이러스 복제 제어의 엄격도를 시험하였다 (도 5). 이러한 세포로는 인간 제대 정맥 세포 (HUVEC), MRC-5 섬유모세포, 대동맥 평활근 세포 (AoMCs), 골격근 세포 (SKMC) 및 CCF-STTG1 성상세포종 세포를 포함하였다. IE1/2-UL51 융합 바이러스에 의해 0.01 pfu/세포의 MOI로 세포를 감염시킨 후 (예외적으로, CCF-STTG1은 5 pfu/세포의 MOI로 감염), 쉴드-1의 존재 또는 부재하에 배지 중에서 인큐베이션시켰다. 모든 세포 유형이 쉴드-1의 존재하에서는 용해성 바이러스 복제를 지원할 수 있었다. 쉴드-1의 부재하에서는 어떤 바이러스 생산도 검출되지 않았다.
실시예
4:
동물에서의
IE1
/2-
UL51
이중 융합 바이러스의 면역원성
마우스, 토끼 및 레서스 원숭이에서 IE1/2-UL51 이중 융합 바이러스의 면역원성을 평가하였다. 먼저 마우스에서의 IE1/2-UL51 이중 융합 바이러스 또는 모 beMAD 바이러스에 대한 용량 의존성 중화 반응을 비교하였다 (도 6a). 0 및 4주째에 6주령된 암컷 BALB/c 마우스를 0.12 ㎍ 내지 10 ㎍ 범위 용량의 beMAD 또는 IE1/2-UL51 이중 융합 바이러스로 면역화시켰다. 6주째부터 혈청 샘플을 수집하고, 이전에 기술된 바와 같이 CMV 미세-중화 검정법에 의해 ARPE-19 세포에 대하여 분석하였다 (문헌 [Tang et al., Vaccine, "A novel throughput neutralization assay for supporting clinical evaluations of human cytomegalovirus vaccines" e-published August 30, 2011 at doi: 10.1016/j.vaccine.2011.08.086]). 0.12, 0.37, 1.1, 3.3 및 10 ㎍ 용량에서의 반응을 비교하였다. 저용량 범위 (0.12 내지 1.1 ㎍)에서, beMAD의 면역원성은 미세하게 좀더 컸고, 이는 투여량 수준이 0.37 ㎍보다 클 경우에 검출되는 중화 항체와 일치하였다. 고용량 범위 (3.3 및 10 ㎍)에서, 두 바이러스에 의해 유도되는 중화 항체 역가는 유사하였다.
이어서, 토끼에서 10 ㎍ 용량의 상이한 바이러스의 면역원성을 비교하였다. 0, 3 및 8주째에 암컷 NZW 토끼를 10 ㎍의 beMAD 또는 지정된 융합 바이러스로 면역화시켰다. 10주째 혈청을 수집하고, CMV 미세-중화 검정법에 의해서 ARPE-19 세포에 대해 분석하였다 (도 5b). beMAD, 단일 융합 바이러스 IE1/2 또는 UL51, 및 이중 융합 바이러스 IE1/2-UL51은 AD169와 유사하지만, 오량체 gH 복합체를 포함하지 않는 바이러스인 MAD169보다 유의적으로 더 높은 역가로 중화 항체를 유도할 수 있었다. 이를 통해 바이러스에 의한 gH 복합체 발현은 재조합 CMV의 면역원성을 유의적으로 증가시킨다는 것을 확인할 수 있었다.
이어서, 레서스 마카크에서 100 ㎍의 이중 융합 IE1/2-UL51 바이러스 또는 모 beMAD 바이러스의 면역원성을 시험하였다. 12주째에 혈청을 수집하고, CMV 미세-중화 검정법에 의해서 ARPE-19 세포에 대해 분석하였다. 12주째 (3차 투여 후) GMT NT50 역가는 각각 11,500 또는 15,600이었다. 상기 역가는 천연적으로 감염된 개체에서 관찰되는 NT50 역가와 유사하였다 (도 5c).
레서스 마카크에서의 이중 융합 바이러스 IE1/2-UL51 CMV 백신-유도성 면역 반응의 수명을 입증하였다. 동물을 (총 단백질 질량에 기초하여) 10 ㎍/용량 또는 100 ㎍/용량의 이중 융합 바이러스 IE1/2-UL51로 백신접종하였다. 비정질 알루미늄 히드록실포스페이트 술페이트 (AAHS) 또는 이스코매트릭스® 아주반트를 포함하는 10 ㎍/용량의 백신 제제 또한 포함하였다. 레서스 마카크 (n=5)에서 0, 8, 및 24주째 백신을 투여하였다. 비교를 위해, 0, 4 및 24주째에 대조군에는 MF59 아주반트와 함께 제제화된 30 ㎍ 용량의 재조합 gB를 투여하였다. 모든 군의 NT50 역가의 역수의 기하 평균 (GMT)이 종방향으로 제시되어 있다 (도 7). 백신접종하기 전에는 어느 원숭이에서도 40을 초과하는 중화 항체 역가는 검출불가능하였다. 모든 군에서 4주째 1차 투여 후 최소의 중화 활성이 검출되었으며, 중화 항체 역가는 약 12주째 및 28주째 (각각 2차 및 3차 백신접종 후 4주 경과하였을 때) 최고치에 도달하였다. 100 ㎍/용량 군에서의 28주째 GMT의 최고치는 14,500 (10 ㎍/용량 군에서의 역가인 4,660보다 약 3배 더 높은 값)이었다. 10 ㎍/용량 군과 비교하였을 때, AAHS가 아닌 이스코매트릭스® 아주반트가 아주반팅 이점을 제공하였다. 이스코매트릭스® 군에서의 28주째 GMT는 15,800인 것으로 측정된 반면, AAHS 군에서는 3,000이고, 10 ㎍/용량 군에서는 4,660이었다. 대조군 (gB/MF59)에 대해서는 최소의 중화 활성이 검출되었고, GMT 최고치는 200을 초과하지 못했다. 연구 72주째인, 0, 8 및 24주째 백신접종 요법을 완료한 후 거의 1년 정도 경과한 시점에, 100 ㎍/용량 군 및 이스코매트릭스® 제제 군에 대한 GMT는 각각 1,400 및 3,000으로 유지되었다. 이 시점에 10 ㎍/용량 군 및 AAHS 군에 대한 GMT는 약 200이었다.
백신접종 요법 28주째 (3차 투여 후 4주 경과하였을 때) 레서스 마카크로부터 말초 혈액 단핵구 세포 (PBMC)를 수집하고, IFN-γ ELISPOT 검정법으로 평가하였다. 100 ㎍/용량 (도 8a) 또는 10 ㎍/용량 (도 8b-8d)의 이중 융합 바이러스 IE1/2-UL51로 원숭이를 백신접종하였다. 추가로, 10 ㎍/용량을 아주반트를 포함하지 않고 (도 8b), 또는 AAHS 아주반트와 함께 (도 8c), 또는 이스코매트릭스® 아주반트와 함께 (도 8d) 제제화하였다. 5개의 HCMV 항원을 나타내는 풀링된 중복 펩티드의 항원을 사용하여 생체외에서 IFN-γ 생산을 자극시켰다. 사용된 HCMV 항원은 IE1 및 IE2 (둘 모두 바이러스 조절 단백질) 및 pp65, gB 및 pp150 (주요 바이러스 구조 항원)이었다. T-세포 반응의 품질은 ELISPOT 반응의 크기 (기하 평균) 뿐만 아니라, 바이러스 항원에 대한 반응자 비율에 의해 평가하였다. 백신접종 이전에는 어떤 원숭이에서도 항원 특이적 ELISPOT 역가는 없었다 (데이터를 나타내지 않음).
28주째, 5가지의 HCMV 항원 (즉, IE1, IE2, pp65, gB 및 pp150)에 대한 ELISPOT 반응의 기하 평균은 각각 100 ㎍/용량 군의 경우, 186, 132, 253, 87, 257개의 반점 형성 세포 (SFC)/106 PBMC 대 10 ㎍/용량 군의 경우, 21, 24, 107, 111, 33개의 SFC/106 PBMC였다 (도 8a 및 8b). 각 군 (n=5)의 반응자를 55개 초과의 SFC/106 PBMC의 컷오프 기준, 및 디메틸 술폭시드 (DMSO) 반응과 비교하여 항원 특이적 반응의 3배 초과 상승에 기초하여 점수화하였다. 5가지의 HCMV 항원 (즉, IE1, IE2, pp65, gB 및 pp150)에 대한 반응자의 개수는 100 ㎍/용량 군의 경우, 4, 4, 5, 1, 3개 대 10 ㎍/용량 군인 경우, 1, 1, 5, 4, 0개였다.
10 ㎍/용량의 이중 융합 바이러스 IE1/2-UL51에의 T-세포 반응에 대하여 이스코매트릭스® 아주반트가 미치는 효과는 도 8d에 제시되어 있다. 5가지의 HCMV 항원 (즉, IE1, IE2, pp65, gB 및 pp150)에 대한 ELISPOT 반응의 기하 평균은 각각 114, 53, 491, 85, 113개의 SFC/106 PBMC였고, 군 (n=5)의 반응자의 개수는 각각 3, 2, 5, 3, 3개였다. 이스코매트릭스® 아주반트를 포함하는 군에서의 T-세포 반응의 크기 및 폭은 100 ㎍/용량 군에서의 것과 유사하였다.
HCMV 항원 (pp65, IE1, IE2 또는 전체 HCMV 비리온)으로 자극시킨 후, 이스코매트릭스®와 함께 (총 단백질 질량에 기초하여) 10 ㎍/용량 또는 100 ㎍/용량의 이중 융합 바이러스 IE1/2-UL51로 백신접종된 동물로부터의 PBMC를 세포내 시토카인 염색법으로 추가로 분석하였다. 음성 대조군은 이중 융합 바이러스 IE1/2-UL51로 백신접종되지 않은 한 나이브 원숭이인 반면, 양성 대조군은 스타필로코쿠스(staphylococcus) 장독소 B (SEB)였다. 도 9에는 음성 대조군이 예상대로, 모든 항원 자극에 대하여 최소의 반응을 보였지만, 양성 대조군 스타필로코쿠스 장독소 B (SEB)에 대해 반응하였다는 것이 제시되어 있다. 상기 두 군 모두로부터의 10마리의 백신접종된 원숭이는 모두 HCMV 특이적 항원에 대하여 유사한 크기 및 패턴으로 반응하였다. 각 항원에 대한 기하 평균 값을 10마리의 원숭이 모두에 대해 산출하였다. 원숭이는 모두 그의 PBMC가 CMV 항원 펩티드 풀 (즉, pp65, IE1 및 IE2)로 자극을 받았을 때, 유사한 CD8+ (도 9a) 및 CD4+ (도 9b) T-세포 반응을 보였지만, 전체 HCMV 비리온으로 자극을 받았을 때에는 우선적으로 CD4+ T-세포 반응을 보였다. 비리온은 단백질 항원이고, 외인성 항원으로서 프로세싱될 가능성이 있으며, MHC 클래스 II 분자에 의해 CD4+ T-세포에게 제시되기 때문에, 상기와 같은 결과는 예상하지 못한 결과였다. 이중 융합 바이러스 IE1/2-UL51은 HCMV 감염을 앓는 건강한 대상체에서 일반적으로 관찰되는 것과 유사한, CD4+ 및 CD8+ 표현형 둘 모두의 T-세포 반응을 유도할 수 있다.
알루미늄 염을 포함하는 이중 융합 바이러스 IE1/2-UL51의 상이한 제제를 레서스 마카크에서 중화 항체를 생성할 수 있는 그의 능력에 대해 비교하였다 (도 10). 30 ㎍/용량의 이중 융합 바이러스 IE1/2-UL51을 HNS (염기 완충제), 비정질 알루미늄 히드록실포스페이트 술페이트 (AAHS) 또는 머크 인산알루미늄 아주반트 (MAPA)와 함께 제제화하고, 0주째 및 8주째 투여하였다. 12주째 수집된 혈청 샘플은, 비록 MAPA가 중화 항체 유도를 증진시키기는 했지만, 그러한 증진은 통계학상 유의적인 것은 아닌 것으로 나타났다 (독립 양측 t 검정).
실시예
5:
보관을 위한
완충제
확인
HBSS (행크의 균형 염 용액) 중의 CMV 바이러스를 적절한 완충제로 ~10x 희석될 때까지 -70℃에서 보관하였다. 각 샘플 중 HBSS 완충제의 나머지 성분으로는 염화칼륨 0.533 mM, 제1인산칼륨 0.044 mM, 제2인산나트륨 0.034 mM, 염화나트륨 13.79 mM, 중탄산나트륨 0.417 mM 및 글루코스 0.1% w/v를 포함하였다. 이어서, 샘플을 실온 또는 2℃-8℃의 온도에서 4일 동안 보관하거나, 동결 해동시켰다. 동결 해동시키는 경우, 1 또는 3회 사이클을 위해 샘플을 -70℃ 1시간 이상 동안 보관하고, RT에서 30분 동안 해동시켰다. 4일째, 바이러스 유입 검정법을 사용하여 샘플의 안정성을 시험하였다. 간략하면, 수개의 상이한 샘플 희석액을 사용하여 검정법을 수행함으로써 반응 곡선을 수득하고, 비선형 곡선 피팅에 의한 바이러스 유입 검정 결과로부터 EC50 (㎍/mL) 값을 수득하였다. EC50 값이 더 낮을수록 안정성은 더 우수한 것으로 나타났다. 안정성 샘플의 EC50 값을 -70℃에서 동결된 대조군 샘플과 비교하였다.
바이러스 유입 검정법은, CMV가 ARPE-19 세포를 감염시키고 IE1 (극초기 단백질 1)을 발현시킬 수 있는 능력을 측정한다. 본 검정법은 투명 96-웰 플레이트에서 수행하였다. IE1 특이적 1차 항체 및 비오틴화된 2차 항체를 사용하여 고정 세포 중의 표적 단백질을 검출하고, (세포 유입 정규화를 위한) 사파이어(Sapphire) 700/DRAQ5와 함께 IR 다이 800CW 스트렙타비딘(IR Dye 800CW Streptavidin)을 사용하여 각 웰로부터의 형광 신호를 정량화하였다. 800/700 통합 강도비 (통합비) 대 CMV 농도 (총 단백질 (㎍/mL))로서 결과를 플롯팅하였다. 비선형 곡선 피팅을 사용하여 감염성 검정 결과로부터 EC50 값 또한 수득하였다. ARPE-19 세포의 바이러스 감염은 바이러스 당단백질 항원, 특히 오량체 gH 복합체의 무결성에 의존하는 바, EC50 값은 바이러스 입자가 상기 조건하에서 얼마나 잘 보존되는지를 반영한다.
도 11에 제시되어 있는 바와 같이, RT에서 4일 동안 HBSS 중에서 보관하였을 때, CMV는 감염성을 상실하였다. 또한, 바이러스 유입 검정법에 의해 평가하였을 때, HBSS 중에서 3회에 걸쳐 수행된 동결로 인해 감염성을 완전히 상실하였다. 따라서, HBSS는 CMV를 보관하는 데 있어 최적의 완충제는 아니었다.
범위가 pH 3 내지 8 범위인 pH를 이용하여 실온에서 pH가 CMV 안정성에 미치는 효과를 조사하였다. 하기 완충제를 사용하였다: 시트레이트 완충제 (25 mM) (pH 3.0); 아세테이트 완충제 (25 mM) (pH 4); 아세테이트 완충제 (25 mM) (pH 5); 히스티딘 완충제 (25 mM) (pH 6); HEPES 완충제 (25 mM) (pH 7; 행크의 균형 염 용액 (HBSS) (pH 7.5) 및 트리스 완충제 (25 mM) (pH 8).
적절한 완충제로 바이러스 벌크를 10배 희석시킴으로써 샘플을 제조하였다. 샘플을 RT (25℃)에서 4일 동안 보관하였다. 4일째, 바이러스 유입 검정법을 사용하여 샘플의 안정성을 측정하였다. -70℃에서 냉동 보관된 HBSS 중의 CMV를 대조군으로서 처리하였다. 보관 동안에 일어난 구조적 변화 및 응집을 조사하기 위해 시점 0 및 4일째에 각 샘플에 대한 UV-Vis 스펙트럼을 수득하였다.
도 12에 제시된 바와 같이, 25 mM 히스티딘 완충제 (pH 6)가 시험된 다른 pH와 비교하여 보다 높은 감염성을 유지함으로써 CMV에 대해 우수한 안정성을 제공하였다. UV-스펙트럼의 제2 유도체는 모든 pH에서 바이러스의 유사한 구조적 프로파일을 나타내었다 (데이터를 나타내지 않음). 350 nm에서의 광학 밀도에 의해 측정된 바, 시험된 pH 중 어느 pH에서도 유의적인 응집은 관찰되지 않았다 (데이터를 나타내지 않음).
25 mM 히스티딘 완충제 (pH 6) 중에서 우레아 단독, 또는 염화나트륨과 함께 조합된 우레아가 CMV 바이러스 안정성에 미치는 효과를 시험하였다. 2% 우레아만 단독으로 첨가하였을 때에는 CMV 안정성에 어떤 영향도 미치지 않았다. 그러나, 2% 우레아를 150 mM NaCl과 함께 조합한 경우, RT에서의 CMV 안정성은 개선되었다 (도 13).
pH 6에서의 이온 강도가 CMV 안정성에 미치는 효과를 조사하였다. 25 mM 히스티딘 완충제 (pH 6)에 NaCl을 농도를 증가시키면서 첨가하였다 (0 mM, 75 mM, 150 mM 및 320 mM NaCl). CMV 안정성은 이온 강도에 의존적이었는데, 이온 강도가 높을수록 안정성은 더 우수하였다 (도 14). 우레아의 존재는 CMV 안정성에 전혀 영향을 미치지 않거나, 또는 최소한의 영향을 미쳤다 (데이터를 나타내지 않음).
추가로, 실온에서 수개의 다른 부형제 (수크로스, 소르비톨, 글리세롤, 및 프롤린)를 그가 gH를 발현하는 CMV 안정성에 미치는 효과에 대해 스크리닝하였다. 시험하고자 하는 부형제를 실온에서 4일 동안 25 mm 히스티딘 완충제 (pH 6) 중의 CMV에 첨가한 후, 바이러스 유입 검정법을 이용하여 CMV 바이러스 안정성을 측정하였다. 샘플에 대한 EC50 값을 계산하였다. 시험된 모든 부형제 중에서 150 mM의 NaCl 단독, 또는 9% w/v 수크로스와 함께 조합된 것이 pH 6에서 우수한 안정성을 제공하였다 (데이터를 나타내지 않음). 그러므로, RT에서의 CMV 보관을 위해 권고되는 완충제는 9% w/v 수크로스를 함유하거나 함유하지 않으며, 150 mM NaCl을 포함하는 25 mM 히스티딘 (pH 6)이었다.
동결-해동 동안 동결보호제가 CMV 안정성에 미치는 효과를 조사하였다. 이전에 언급된 바와 같이 (도 11), 3회에 걸쳐 동결-해동 사이클을 수행하였을 때, HBSS 중의 CMV는 그의 감염성을 완전히 상실하였다. CMV에 가중되는 동결-해동 스트레스를 감소시킬 수 있는 능력에 대하여 수개의 동결보호제 (수크로스, 소르비톨, 글리세롤 포함)를 스크리닝하였다. 각 동결-해동 사이클에서 샘플을 -70℃에서 1시간 이상 동안 동결시키고, RT에서 30분 동안 해동시켰다. 동결보호제를 첨가한 결과, 바이러스의 안정성은 증가하였다. 또한, 시험된 다른 동결보호제와 비교하였을 때, 150 mM 염화나트륨와 함께 조합된 9% w/v 수크로스를 통해서는 바이러스의 안정성은 유의적으로 증진되었다 (도 15). 그러므로, -70℃에서 CMV를 보관하거나, 최대 3회까지 동결-해동 사이클을 수행하는 데 권고되는 완충제 조성물은 25 mM 히스티딘, 150 mM NaCl 및 9% 수크로스 (HNS 완충제)였다.
3회에 걸친 동결-해동 사이클 동안, 냉장 (2-8℃) 및 RT (25℃)에서 CMV 안정성 보호에 대해 HNS 완충제를 HBSS 완충제와 비교하였다. 시험된 모든 보관 조건에서 HNS 완충제가 CMV 생 바이러스에 대해 우수한 안정성을 제공하였다 (데이터를 나타내지 않음).
실시예
6:
HNS
완중체
중에서의
CMV
안정성
이중 융합 IE1/2-UL51 CMV 바이러스 스톡을 HNS 완충제에 공급하고, 사용시까지 -70℃에서 보관하였다. (브래드포드 검정법에 의해 측정된 총 단백질 함량에 기초하여) 100 ㎍/mL의 농도로 안정성 연구를 수행하였다. 벌크 바이러스를 HNS 완충제로 희석시켜 최종 바이러스 농도를 수득하였다. 이어서, 샘플을 적절한 온도에서 보관하고, 최대 3개월 동안 기술된 바와 같이 시험하였다. 동결-해동을 위해, 샘플을 1시간 이상 동안 -70℃에서 동결시키고, 실온에서 30분 동안 해동시켰다. 상이한 시점에 샘플을 채취하여, 분석시까지 -70℃에서 냉동 보관하였다.
브래드포드 검정법을 사용하여 샘플의 총 단백질 함량을 측정하였다. 샘플의 총 단백질 함량은 3개월 동안에 걸쳐 변하지 않았다 (데이터를 나타내지 않음).
DLS 방법을 사용하여 샘플의 수력학적 직경을 측정함으로써 시간 경과에 따른 샘플 중의 CMV의 입자 크기를 모니터링하였다. 상기 방법을 통해 상이한 보관 온도에서 시간 경과에 따른 바이러스 입자의 임의의 응집 또는 파괴를 모니터링하였다. 특정 샘플의 입자 크기에 있어 산발성 변화가 있었지만, 어떤 실제적인 경향은 관찰되지 않았다 (데이터를 나타내지 않음). 본 결과는 바이러스 입자가 무손상이고, 승온에서 응집되지 않았다는 것을 시사한다.
실시예
7:
보관 조건이 바이러스 유입 및 면역원성에 미치는 효과
CMV 샘플을 상이한 보관 온도에 가함으로써 바이러스 유입 역가 (EC50 값)의 유의적인 변화를 관찰하였다. -20℃에서 보관함으로써 바이러스 유입 역가는 2-8℃ 및 25℃에서의 경우에 비하여 저하되었다. 2-8℃ 샘플의 역가는 25℃에서 보관한 것과 비교하였을 때, 더 낮은 바이러스 유입 역가인 것으로 나타났다. EC50 값에 기초하여, 보관 온도는 하기 순서로 (가장 안정적인 것에서부터 가장 덜 안정적인 순서) 순위화되었다: 25℃ > 2-8℃ > -20℃ (최대 1개월째 되는 시점까지). -20℃, 2-8℃ 및 25℃에서 보관된 샘플의 경우, 3개월째 되는 시점에서는 바이러스 유입 역가가 검출되지 않았다.
CMV가 CMV 중화 항체를 유도할 수 있는 능력에 대하여 보관 온도가 미치는 효과를 측정하기 위하여 안정성 연구 종료시 마우스 면역원성 연구를 개시하였다. 마우스를 0일째 2.5 ㎍/용량의 백신으로 i.m.으로 면역화시키고, 21일째 추가접종한 후, 28일째 출혈시켰다. ARPE-19 세포를 사용하여 마우스 혈청을 gH를 발현하는 CMV에 대한 중화 항체에 대하여 시험하고, 비선형 곡선 피팅에 의해 NT50 역가를 수득하였다.
상이한 온도에서의 3개월 동안의 보관이 IE1/2-UL51 이중 융합 CMV 면역원성에 미치는 효과를 평가하였다. NT50 역가는 보관 온도에 의존적이었는데, 비록 유의적이지는 않았지만, -70℃에서 동결된 대조군과 비교해 보면, 온도가 높을수록 역가는 감소하는 것으로 나타났다 (p=0.2584, 일원 ANOVA) (도 16a). -20℃에서 보관된 제제의 NT50 역가가 2배 미만 만큼 더 낮았지만, 상기 샘플의 바이러스 유입 검정 역가는 -70℃에서 동결된 대조군과 비교해 보면, 유의적인 영향을 받은 것으로 나타났다. -20℃, 2-8℃ 및 25℃ 안정성 샘플에 대한 NT50 역가 경향은 상기 샘플에 대해 수득된 CMV 질량 ELISA 역가를 따르는 것으로 나타났다.
해동 후, 8시간 동안의 상이한 온도에서의 보관이 IE1/2-UL51 이중 융합 CMV 면역원성에 미치는 효과를 평가하였다. 제제의 NT50 역가를 70℃에서 동결된 대조군과 비교하였다. 시험된 온도 중 임의의 온도에서 8시간 동안 샘플을 보관함으로써 NT50 역가는 어떤 영향도 받지 않았다 (p=0.5865, 일원 ANOVA) (도 16b).
해동 후, 상이한 시점 동안 25℃에서 이중 융합 IE1/2-UL51 CMV를 보관하는 것이 미치는 효과를 마우스 면역원성 연구에서 평가하였다. 상기 제제의 NT50 역가를 -70℃에서 동결된 대조군과 비교하였다. 샘플을 25℃에서 최대 1주 동안 보관함으로써 NT50 역가는 어떤 영향도 받지 않았다 (p=0.1848, 독립 양측 t 검정). 3개월째 NT50 역가는 2배 초과로 근소하게 하락하였는 데, 이는 제제를 25℃에서 보다 장기간 동안 보관하는 것도 안정성 문제에 있어서는 가능한 일이라는 것을 시사하는 것이다 (데이터를 나타내지 않음).
3회에 걸쳐 동결-해동 사이클을 수행하는 것이 HNS 완충제 중에서 제제화된 이중 융합 IE1/2-UL51 CMV에 미치는 효과를 마우스 면역원성에 의해 평가하였다. -70℃에서 동결된 대조군과 비교하였을 때, 이중 융합 CMV 제제를 3회에 걸쳐 동결-해동 (F/T)시켜도 면역원성에는 어떤 영향도 주지 않았다 (p=0.2103, 독립 양측 t 검정) (데이터를 나타내지 않음).
다른 실시양태는 하기 특허청구범위 내에 포함된다. 수개의 실시양태를 제시하고 기술하였지만, 본 발명의 취지 및 범주로부터 벗어남 없이 다양하게 변형될 수 있다.
SEQUENCE LISTING
<110> Tong-Ming FU
Dai WANG
Muneeswara Babu MEDI
<120> CONDITIONAL REPLICATING CYTOMEGALOVIRUS
AS A VACCINE FOR CMV
<130> 23109-US-PCT
<150> 61/532,667
<151> 2011-09-09
<160> 14
<170> FastSEQ for Windows Version 4.0
<210> 1
<211> 598
<212> PRT
<213> Artificial Sequence
<220>
<223> Chemically Synthesized
<400> 1
Met Gly Val Gln Val Glu Thr Ile Ser Pro Gly Asp Gly Arg Thr Phe
1 5 10 15
Pro Lys Arg Gly Gln Thr Cys Val Val His Tyr Thr Gly Met Leu Glu
20 25 30
Asp Gly Lys Lys Val Asp Ser Ser Arg Asp Arg Asn Lys Pro Phe Lys
35 40 45
Phe Met Leu Gly Lys Gln Glu Val Ile Arg Gly Trp Glu Glu Gly Val
50 55 60
Ala Gln Met Ser Val Gly Gln Arg Ala Lys Leu Thr Ile Ser Pro Asp
65 70 75 80
Tyr Ala Tyr Gly Ala Thr Gly His Pro Gly Ile Ile Pro Pro His Ala
85 90 95
Thr Leu Val Phe Asp Val Glu Leu Leu Lys Pro Glu Glu Ser Ser Ala
100 105 110
Lys Arg Lys Met Asp Pro Asp Asn Pro Asp Glu Gly Pro Ser Ser Lys
115 120 125
Val Pro Arg Pro Glu Thr Pro Val Thr Lys Ala Thr Thr Phe Leu Gln
130 135 140
Thr Met Leu Arg Lys Glu Val Asn Ser Gln Leu Ser Leu Gly Asp Pro
145 150 155 160
Leu Phe Pro Glu Leu Ala Glu Glu Ser Leu Lys Thr Phe Glu Gln Val
165 170 175
Thr Glu Asp Cys Asn Glu Asn Pro Glu Lys Asp Val Leu Ala Glu Leu
180 185 190
Val Lys Gln Ile Lys Val Arg Val Asp Met Val Arg His Arg Ile Lys
195 200 205
Glu His Met Leu Lys Lys Tyr Thr Gln Thr Glu Glu Lys Phe Thr Gly
210 215 220
Ala Phe Asn Met Met Gly Gly Cys Leu Gln Asn Ala Leu Asp Ile Leu
225 230 235 240
Asp Lys Val His Glu Pro Phe Glu Glu Met Lys Cys Ile Gly Leu Thr
245 250 255
Met Gln Ser Met Tyr Glu Asn Tyr Ile Val Pro Glu Asp Lys Arg Glu
260 265 270
Met Trp Met Ala Cys Ile Lys Glu Leu His Asp Val Ser Lys Gly Ala
275 280 285
Ala Asn Lys Leu Gly Gly Ala Leu Gln Ala Lys Ala Arg Ala Lys Lys
290 295 300
Asp Glu Leu Arg Arg Lys Met Met Tyr Met Cys Tyr Arg Asn Ile Glu
305 310 315 320
Phe Phe Thr Lys Asn Ser Ala Phe Pro Lys Thr Thr Asn Gly Cys Ser
325 330 335
Gln Ala Met Ala Ala Leu Gln Asn Leu Pro Gln Cys Ser Pro Asp Glu
340 345 350
Ile Met Ala Tyr Ala Gln Lys Ile Phe Lys Ile Leu Asp Glu Glu Arg
355 360 365
Asp Lys Val Leu Thr His Ile Asp His Ile Phe Met Asp Ile Leu Thr
370 375 380
Thr Cys Val Glu Thr Met Cys Asn Glu Tyr Lys Val Thr Ser Asp Ala
385 390 395 400
Cys Met Met Thr Met Tyr Gly Gly Ile Ser Leu Leu Ser Glu Phe Cys
405 410 415
Arg Val Leu Cys Cys Tyr Val Leu Glu Glu Thr Ser Val Met Leu Ala
420 425 430
Lys Arg Pro Leu Ile Thr Lys Pro Glu Val Ile Ser Val Met Lys Arg
435 440 445
Arg Ile Glu Glu Ile Cys Met Lys Val Phe Ala Gln Tyr Ile Leu Gly
450 455 460
Ala Asp Pro Leu Arg Val Cys Ser Pro Ser Val Asp Asp Leu Arg Ala
465 470 475 480
Ile Ala Glu Glu Ser Asp Glu Glu Glu Ala Ile Val Ala Tyr Thr Leu
485 490 495
Ala Thr Ala Gly Val Ser Ser Ser Asp Ser Leu Val Ser Pro Pro Glu
500 505 510
Ser Pro Val Pro Ala Thr Ile Pro Leu Ser Ser Val Ile Val Ala Glu
515 520 525
Asn Ser Asp Gln Glu Glu Ser Glu Gln Ser Asp Glu Glu Glu Glu Glu
530 535 540
Gly Ala Gln Glu Glu Arg Glu Asp Thr Val Ser Val Lys Ser Glu Pro
545 550 555 560
Val Ser Glu Ile Glu Glu Val Ala Pro Glu Glu Glu Glu Asp Gly Ala
565 570 575
Glu Glu Pro Thr Ala Ser Gly Gly Lys Ser Thr His Pro Met Val Thr
580 585 590
Arg Ser Lys Ala Asp Gln
595
<210> 2
<211> 2081
<212> DNA
<213> Artificial Sequence
<220>
<223> Chemically Synthesized
<400> 2
atgggagtgc aggtggaaac catctcccca ggagacgggc gcaccttccc caagcgcggc 60
cagacctgtg tggtgcacta caccgggatg cttgaagatg gaaagaaagt cgattcctcc 120
cgggacagaa acaagccctt taagtttatg ctaggcaagc aggaggtgat ccgaggctgg 180
gaagaagggg ttgcccagat gagtgtgggt cagagagcca aactgactat atctccagat 240
tatgcctatg gtgccactgg gcacccaggc atcatcccac cacatgccac tctcgtcttc 300
gatgtggagc ttctaaaacc ggaagagtcc tctgccaaga gaaagatgga ccctgataat 360
cctgacgagg gcccttcctc caaggtgcca cggtacgtgt cggggtttgt gccccccctt 420
tttttttaat aaaattgtat taatgttata tacatatctc ctgtatgtga cccatgtgct 480
tatgactcta tttctcatgt gtttaggccc gagacacccg tgaccaaggc cacgacgttc 540
ctgcagacta tgttgaggaa ggaggttaac agtcagctga gtctgggaga cccgctgttt 600
ccagagttgg ccgaagaatc cctcaaaact tttgaacaag tgaccgagga ttgcaacgag 660
aaccccgaga aagatgtcct ggcagaactc ggtaagtctg ttgacatgta tgtgatgtat 720
actaacctgc atgggacgtg gatttacttg tgtatgtcag atagagtaaa gattaactct 780
tgcatgtgag cggggcatcg agatagcgat aaatgagtca ggaggacgga tacttatatg 840
tgttgttatc ctcctctaca gtcaaacaga ttaaggttcg agtggacatg gtgcggcata 900
gaatcaagga gcacatgctg aaaaaatata cccagacgga agagaaattc actggcgcct 960
ttaatatgat gggaggatgt ttgcagaatg ccttagatat cttagataag gttcatgagc 1020
ctttcgagga gatgaagtgt attgggctaa ctatgcagag catgtatgag aactacattg 1080
tacctgagga taagcgggag atgtggatgg cttgtattaa ggagctgcat gatgtgagca 1140
agggcgccgc taacaagttg gggggtgcac tgcaggctaa ggcccgtgct aaaaaggatg 1200
aacttaggag aaagatgatg tatatgtgct acaggaatat agagttcttt accaagaact 1260
cagccttccc taagaccacc aatggctgca gtcaggccat ggcggcactg cagaacttgc 1320
ctcagtgctc ccctgatgag attatggctt atgcccagaa aatatttaag attttggatg 1380
aggagagaga caaggtgctc acgcacattg atcacatatt tatggatatc ctcactacat 1440
gtgtggaaac aatgtgtaat gagtacaagg tcactagtga cgcttgtatg atgaccatgt 1500
acgggggcat ctctctctta agtgagttct gtcgggtgct gtgctgctat gtcttagagg 1560
agactagtgt gatgctggcc aagcggcctc tgataaccaa gcctgaggtt atcagtgtaa 1620
tgaagcgccg cattgaggag atctgcatga aggtctttgc ccagtacatt ctgggggccg 1680
atcctctgag agtctgctct cctagtgtgg atgacctacg ggccatcgcc gaggagtcag 1740
atgaggaaga ggctattgta gcctacactt tggccaccgc tggtgtcagc tcctctgatt 1800
ctctggtgtc acccccagag tcccctgtac ccgcgactat ccctctgtcc tcagtaattg 1860
tggctgagaa cagtgatcag gaagaaagtg agcagagtga tgaggaagag gaggagggtg 1920
ctcaggagga gcgggaggac actgtgtctg tcaagtctga gccagtgtct gagatagagg 1980
aagttgcccc agaggaagag gaggatggtg ctgaggaacc caccgcctct ggaggcaaga 2040
gcacccaccc tatggtgact agaagcaagg ctgaccagta a 2081
<210> 3
<211> 264
<212> PRT
<213> Artificial Sequence
<220>
<223> Chemically Synthesized
<400> 3
Met Gly Val Gln Val Glu Thr Ile Ser Pro Gly Asp Gly Arg Thr Phe
1 5 10 15
Pro Lys Arg Gly Gln Thr Cys Val Val His Tyr Thr Gly Met Leu Glu
20 25 30
Asp Gly Lys Lys Val Asp Ser Ser Arg Asp Arg Asn Lys Pro Phe Lys
35 40 45
Phe Met Leu Gly Lys Gln Glu Val Ile Arg Gly Trp Glu Glu Gly Val
50 55 60
Ala Gln Met Ser Val Gly Gln Arg Ala Lys Leu Thr Ile Ser Pro Asp
65 70 75 80
Tyr Ala Tyr Gly Ala Thr Gly His Pro Gly Ile Ile Pro Pro His Ala
85 90 95
Thr Leu Val Phe Asp Val Glu Leu Leu Lys Pro Glu Ser Trp Ala Lys
100 105 110
Gln Arg Val Pro Phe Leu Asp Asp Asp Asp Gly Glu Glu Glu Asn Asp
115 120 125
Val Gln Asp Asp Val Asp Ser Pro Val Pro Thr Arg Pro Leu Val Ile
130 135 140
Asp Glu Asp Ala Glu Pro Ala Ala Gly Thr Ser Gly Gly Leu Glu Gly
145 150 155 160
Gly Gly Gly Asp Asp Glu Asp Gly Glu Asp Gly His Ala Leu Pro Asp
165 170 175
Leu Asp Asp Asp Leu Leu Leu Gln Phe Glu Pro Met Leu Pro Arg Val
180 185 190
Tyr Asp Leu Leu Leu Pro Ser Leu Asp Ala Arg Leu Asn Phe Val Asn
195 200 205
Ala Gly Gln Lys Tyr Ala Ala Phe Leu Lys Tyr Val His Gly Asp Cys
210 215 220
Ala Thr Cys Ser His Gly Glu Ile Leu Arg Glu Lys Thr Gln Leu Leu
225 230 235 240
Thr Ala Ile Val Ser Lys Leu Met Asp Ile Asn Gly Ile Leu Glu Gly
245 250 255
Lys Asp Glu Ser Ala Pro Gly Lys
260
<210> 4
<211> 795
<212> DNA
<213> Artificial Sequence
<220>
<223> Chemically Synthesized
<400> 4
atgggagtgc aggtggaaac catctcccca ggagacgggc gcaccttccc caagcgcggc 60
cagacctgtg tggtgcacta caccgggatg cttgaagatg gaaagaaagt cgattcctcc 120
cgggacagaa acaagccctt taagtttatg ctaggcaagc aggaggtgat ccgaggctgg 180
gaagaagggg ttgcccagat gagtgtgggt cagagagcca aactgactat atctccagat 240
tatgcctatg gtgccactgg gcacccaggc atcatcccac cacatgccac tctcgtcttc 300
gatgtggagc ttctaaaacc ggaatcctgg gctaagcagc gggtgccgtt tctggacgat 360
gacgacggag aggaggaaaa cgacgtgcag gatgacgtgg attctccggt gccgacgcga 420
ccgctggtga tcgacgagga cgcggagccc gcggctggta cgagcggtgg gctcgagggg 480
ggaggtggtg acgacgagga cggtgaagac ggacacgcgc tacccgatct tgacgacgat 540
ctgctattac agttcgagcc gatgctgccg cgcgtctacg atctgttgct gccctctctg 600
gacgcgcgct taaatttcgt gaacgcgggt cagaagtacg ccgccttcct caagtacgtg 660
cacggcgact gcgcgacctg cagtcacgga gagatcctcc gtgagaagac gcaactatta 720
acggcgatcg tcagcaagct catggacatt aacggaatcc tggagggaaa agacgagtcg 780
gcgccgggta aataa 795
<210> 5
<211> 775
<212> PRT
<213> Artificial Sequence
<220>
<223> Chemically Synthesized
<400> 5
Met Gly Val Gln Val Glu Thr Ile Ser Pro Gly Asp Gly Arg Thr Phe
1 5 10 15
Pro Lys Arg Gly Gln Thr Cys Val Val His Tyr Thr Gly Met Leu Glu
20 25 30
Asp Gly Lys Lys Val Asp Ser Ser Arg Asp Arg Asn Lys Pro Phe Lys
35 40 45
Phe Met Leu Gly Lys Gln Glu Val Ile Arg Gly Trp Glu Glu Gly Val
50 55 60
Ala Gln Met Ser Val Gly Gln Arg Ala Lys Leu Thr Ile Ser Pro Asp
65 70 75 80
Tyr Ala Tyr Gly Ala Thr Gly His Pro Gly Ile Ile Pro Pro His Ala
85 90 95
Thr Leu Val Phe Asp Val Glu Leu Leu Lys Pro Glu Asn Pro Ser Thr
100 105 110
His Val Ser Ser Asn Gly Pro Thr Thr Pro Pro His Gly Pro His Thr
115 120 125
Thr Phe Leu Pro Pro Thr Ser Pro Ala Pro Ser Thr Ser Ser Val Ala
130 135 140
Ala Ala Thr Leu Cys Ser Pro Gln Arg Gln Ala Val Ser Arg Tyr Ser
145 150 155 160
Gly Trp Ser Thr Glu Tyr Thr Gln Trp His Ser Asp Leu Thr Thr Glu
165 170 175
Leu Leu Trp His Ala His Pro Arg Gln Val Pro Met Asp Glu Ala Leu
180 185 190
Ala Ala Ala Ala Ala Ala Ser Tyr Gln Val Asn Pro Gln His Pro Ala
195 200 205
Asn Arg Tyr Arg His Tyr Glu Phe Gln Thr Leu Ser Leu Gly Thr Ser
210 215 220
Glu Val Asp Glu Leu Leu Asn Cys Cys Ala Glu Glu Thr Thr Cys Gly
225 230 235 240
Gly Thr Gln Ser Thr Val Leu Thr Asn Ala Thr Asn Thr Thr Ser Cys
245 250 255
Gly Gly Ala Val Ala Gly Ser Ser Asn Val Gly Pro Ala Gly Ala Ser
260 265 270
Ala Ala Cys Asp Leu Asp Ala Glu Leu Ala Gly Leu Glu Thr Ser Ala
275 280 285
Ala Asp Phe Glu Gln Leu Arg Arg Leu Cys Ala Pro Leu Ala Ile Asp
290 295 300
Thr Arg Cys Asn Leu Cys Ala Ile Ile Ser Ile Cys Leu Lys Gln Asp
305 310 315 320
Cys Asp Gln Ser Trp Leu Leu Glu Tyr Ser Leu Leu Cys Phe Lys Cys
325 330 335
Ser Tyr Ala Pro Arg Ala Ala Leu Ser Thr Leu Ile Ile Met Ser Glu
340 345 350
Phe Thr His Leu Leu Gln Gln His Phe Ser Asp Leu Arg Ile Asp Asp
355 360 365
Leu Phe Arg His His Val Leu Thr Val Phe Asp Phe His Leu His Phe
370 375 380
Phe Ile Asn Arg Cys Phe Glu Lys Gln Val Gly Asp Ala Val Asp Asn
385 390 395 400
Glu Asn Val Thr Leu Asn His Leu Ala Val Val Arg Ala Met Val Met
405 410 415
Gly Glu Asp Thr Val Pro Tyr Asn Lys Pro Arg Arg His Pro Gln Gln
420 425 430
Lys Gln Lys Asn Asn Pro Tyr His Val Glu Val Pro Gln Glu Leu Ile
435 440 445
Asp Asn Phe Leu Glu His Ser Ser Pro Ser Arg Asp Arg Phe Val Gln
450 455 460
Leu Leu Phe Tyr Met Trp Ala Gly Thr Gly Val Met Ser Thr Thr Pro
465 470 475 480
Leu Thr Glu Leu Thr His Thr Lys Phe Ala Arg Leu Asp Ala Leu Ser
485 490 495
Thr Ala Ser Glu Arg Glu Asp Ala Arg Met Met Ile Glu Glu Glu Glu
500 505 510
Asp Glu Glu Gly Gly Glu Lys Gly Gly Asp Asp Pro Gly Arg His Asn
515 520 525
Gly Gly Gly Thr Ser Gly Gly Phe Ser Glu Ser Thr Leu Lys Lys Asn
530 535 540
Val Gly Pro Ile Tyr Leu Cys Pro Val Pro Ala Phe Phe Thr Lys Asn
545 550 555 560
Gln Thr Ser Thr Val Cys Leu Leu Cys Glu Leu Met Ala Cys Ser Tyr
565 570 575
Tyr Asp Asn Val Val Leu Arg Glu Leu Tyr Arg Arg Val Val Ser Tyr
580 585 590
Cys Gln Asn Asn Val Lys Met Val Asp Arg Ile Gln Leu Val Leu Ala
595 600 605
Asp Leu Leu Arg Glu Cys Thr Ser Pro Leu Gly Ala Ala His Glu Asp
610 615 620
Val Ala Arg Cys Gly Leu Glu Ala Pro Thr Ser Pro Gly Gly Asp Ser
625 630 635 640
Asp Tyr His Gly Leu Ser Gly Val Asp Gly Ala Leu Ala Arg Pro Asp
645 650 655
Pro Val Phe Cys His Val Leu Arg Gln Ala Gly Val Thr Gly Ile Tyr
660 665 670
Lys His Phe Phe Cys Asp Pro Gln Cys Ala Gly Asn Ile Arg Val Thr
675 680 685
Asn Glu Ala Val Leu Phe Gly Arg Leu His Pro His His Val Gln Glu
690 695 700
Val Lys Leu Ala Ile Cys His Asp Asn Tyr Tyr Ile Ser Arg Leu Pro
705 710 715 720
Arg Arg Val Trp Leu Cys Ile Thr Leu Phe Lys Ala Phe Gln Ile Thr
725 730 735
Lys Arg Thr Tyr Lys Gly Lys Val His Leu Ala Asp Phe Met Arg Asp
740 745 750
Phe Thr Gln Leu Leu Glu Ser Cys Asp Ile Lys Leu Val Asp Pro Thr
755 760 765
Tyr Val Ile Asp Lys Tyr Val
770 775
<210> 6
<211> 2328
<212> DNA
<213> Artificial Sequence
<220>
<223> Chemically Synthesized
<400> 6
atgggagtgc aggtggaaac catctcccca ggagacgggc gcaccttccc caagcgcggc 60
cagacctgtg tggtgcacta caccgggatg cttgaagatg gaaagaaagt cgattcctcc 120
cgggacagaa acaagccctt taagtttatg ctaggcaagc aggaggtgat ccgaggctgg 180
gaagaagggg ttgcccagat gagtgtgggt cagagagcca aactgactat atctccagat 240
tatgcctatg gtgccactgg gcacccaggc atcatcccac cacatgccac tctcgtcttc 300
gatgtggagc ttctaaaacc ggaaaatccg agtacccacg tgagcagtaa cggcccaacg 360
actccccctc acgggcccca caccacgttt cttcccccga ccagcccggc cccgtccacc 420
agctccgtcg ccgccgctac cttgtgcagt ccgcaacgac aggccgtttc gcgttacagc 480
ggctggagca ccgagtacac ccagtggcac tcggacttga caactgagct gctatggcac 540
gcgcacccgc gtcaagtacc tatggacgaa gcgctggccg ccgcggcggc cgcctcatac 600
caggtaaatc ctcaacaccc cgccaaccgt taccgtcatt acgaattcca gacgctcagc 660
ctcggcacct cggaggtaga cgaactgctc aactgttgtg cggaagaaac cacgtgcggc 720
ggcacgcaat ccaccgtact caccaatgcg accaacacca ctagctgcgg cggagccgtc 780
gccggcagta gcaacgtagg acccgccggc gcttcggccg cctgcgacct agatgcagaa 840
ctggccggcc tcgaaacctc ggcggccgac tttgaacaac tgcggcgact gtgcgcgccg 900
ctggccatcg acacgcgctg taacctatgc gccatcatca gcatctgcct caaacaggac 960
tgcgaccaga gctggctcct cgagtacagc ttgctgtgct tcaaatgcag ttacgcgccc 1020
cgtgcggcgc tcagcacgct catcatcatg tccgagttta cgcatctgct gcagcagcac 1080
ttttccgatc tgcgcatcga cgacctgttc cgacaccacg ttctcacggt cttcgatttc 1140
cacctgcact ttttcatcaa tcgttgcttt gaaaaacaag tgggcgacgc ggttgataac 1200
gagaatgtca ccctgaacca tctggccgtg gtgcgggcca tggtcatggg tgaagacacg 1260
gtgccttaca acaagcctcg gcgccacccg caacagaagc aaaaaaacaa cccttatcac 1320
gtcgaagtgc cgcaagaact gatcgacaac tttctagaac acagctcacc tagccgcgac 1380
cgcttcgtgc agctgctttt ctatatgtgg gccggcaccg gcgtcatgag caccacgcca 1440
ctcacggaac tcacgcacac taagttcgcg cgactagacg cgttatccac ggcctcggaa 1500
agagaagacg caaggatgat gatagaagaa gaggaggatg aagaaggagg agaaaaagga 1560
ggagacgatc cgggccgtca caacggcggt ggcaccagcg gggggttcag cgagagcacg 1620
ctaaaaaaaa acgtgggtcc catttaccta tgtcccgtac ccgctttttt taccaagaac 1680
caaaccagta ccgtgtgtct gctgtgcgaa ctcatggcct gctcctatta cgataacgtc 1740
gtcctgcgcg agctgtaccg ccgcgtcgtc tcgtattgtc agaacaatgt gaagatggtg 1800
gaccgcattc agctggtatt ggccgatctg ttgcgcgaat gcacgtcgcc gctcggcgcg 1860
gcacacgagg acgtggcgcg ctgtggactc gaagcaccca cctcgcccgg aggcgactcg 1920
gactaccacg gcctgagcgg cgtcgacggc gcactggcgc gacccgaccc ggtattttgc 1980
cacgtcctgc gtcaggcagg cgtcacgggc atctacaagc actttttctg cgacccgcag 2040
tgcgccggca acatccgcgt caccaacgag gccgtgctct tcggacgcct gcacccccac 2100
cacgtccagg aggtgaaact ggccatctgt cacgacaatt actatataag tcgacttccg 2160
cgacgtgtgt ggctctgcat cacactcttc aaggcctttc agattacaaa acgcacctac 2220
aaaggcaaag tgcacctggc ggactttatg cgcgatttca cgcagctgtt ggagagttgc 2280
gacatcaagc tggtggaccc cacgtacgtg atagacaagt atgtctag 2328
<210> 7
<211> 402
<212> PRT
<213> Artificial Sequence
<220>
<223> Chemically Synthesized
<400> 7
Met Gly Val Gln Val Glu Thr Ile Ser Pro Gly Asp Gly Arg Thr Phe
1 5 10 15
Pro Lys Arg Gly Gln Thr Cys Val Val His Tyr Thr Gly Met Leu Glu
20 25 30
Asp Gly Lys Lys Val Asp Ser Ser Arg Asp Arg Asn Lys Pro Phe Lys
35 40 45
Phe Met Leu Gly Lys Gln Glu Val Ile Arg Gly Trp Glu Glu Gly Val
50 55 60
Ala Gln Met Ser Val Gly Gln Arg Ala Lys Leu Thr Ile Ser Pro Asp
65 70 75 80
Tyr Ala Tyr Gly Ala Thr Gly His Pro Gly Ile Ile Pro Pro His Ala
85 90 95
Thr Leu Val Phe Asp Val Glu Leu Leu Lys Pro Glu Met Ala Arg Asp
100 105 110
Glu Glu Asn Pro Ala Val Pro Arg Val Arg Thr Gly Lys Phe Ser Phe
115 120 125
Thr Cys Ala Asn His Leu Ile Leu Gln Ile Ser Glu Lys Met Ser Arg
130 135 140
Gly Gln Pro Leu Ser Ser Leu Arg Leu Glu Glu Leu Lys Ile Val Arg
145 150 155 160
Leu Ile Cys Val Leu Leu Phe His Arg Gly Leu Glu Thr Leu Leu Leu
165 170 175
Arg Glu Thr Met Asn Asn Leu Gly Val Ser Asp His Ala Val Leu Ser
180 185 190
Arg Lys Thr Pro Gln Pro Tyr Trp Pro His Leu Tyr Arg Glu Leu Arg
195 200 205
Gln Ala Phe Pro Gly Leu Asp Phe Glu Ala Ala Val Phe Asp Glu Thr
210 215 220
Arg Ala Ala Arg Leu Ser Gln Arg Leu Cys His Pro Arg Leu Ser Gly
225 230 235 240
Gly Leu Leu Thr Arg Phe Val Gln Arg His Thr Gly Leu Pro Val Val
245 250 255
Phe Pro Glu Asp Leu Ala Arg Asn Gly Asn Ile Leu Phe Ser Leu Gly
260 265 270
Thr Leu Tyr Gly His Arg Leu Phe Arg Leu Ala Ala Phe Phe Thr Arg
275 280 285
His Trp Gly Ala Glu Ala Tyr Glu Pro Leu Ile Arg Ile Ile Cys Gln
290 295 300
Lys Met Trp Tyr Phe Tyr Leu Ile Gly Thr Gly Lys Met Arg Ile Thr
305 310 315 320
Pro Asp Ala Phe Glu Ile Gln Arg Ser Arg His Glu Thr Gly Ile Phe
325 330 335
Thr Phe Ile Met Glu Asp Tyr Arg Thr Phe Ala Gly Thr Leu Ser Arg
340 345 350
His Pro His Arg Pro His Pro Gln Gln Gln Gln His His His Pro Gly
355 360 365
Pro Pro His Pro Pro Leu Ser His Pro Ala Ser Ser Cys Leu Ser Pro
370 375 380
Glu Ala Val Leu Ala Ala Arg Ala Leu His Met Pro Thr Leu Ala Asn
385 390 395 400
Asp Val
<210> 8
<211> 1209
<212> DNA
<213> Artificial Sequence
<220>
<223> Chemically Synthesized
<400> 8
atgggagtgc aggtggaaac catctcccca ggagacgggc gcaccttccc caagcgcggc 60
cagacctgtg tggtgcacta caccgggatg cttgaagatg gaaagaaagt cgattcctcc 120
cgggacagaa acaagccctt taagtttatg ctaggcaagc aggaggtgat ccgaggctgg 180
gaagaagggg ttgcccagat gagtgtgggt cagagagcca aactgactat atctccagat 240
tatgcctatg gtgccactgg gcacccaggc atcatcccac cacatgccac tctcgtcttc 300
gatgtggagc ttctaaaacc ggaaatggcc cgcgacgaag agaaccccgc cgtcccgcgg 360
gtccgcacgg gcaaattctc ctttacttgc gccaatcatc taatattaca gattagcgag 420
aagatgtcgc gcggacagcc gctgagctcg ctgcgtttgg aagaactcaa gatcgtacgc 480
ctcatctgcg tcctcctctt tcaccgcggt ctcgaaacgc tgctactgcg cgaaaccatg 540
aacaacctgg gtgtctcgga ccacgccgtg cttagtcgca agacgccgca accctactgg 600
cctcatctgt accgcgaact gcgccaggcc ttcccggggc tggactttga ggcggccgtg 660
ttcgatgaaa cgcgcgccgc ccgtctcagc cagcgcctgt gtcacccgcg cttgagcggc 720
ggactgctga cgcgctttgt gcagcgccac accggcctgc cggtcgtttt ccccgaagac 780
ctggcgcgca acggcaacat cctcttctcc ctaggcacgc tctacggaca ccgcttgttt 840
cgtctggcgg ccttcttcac gcgccactgg ggtgccgaag cgtacgaacc cttgattcgc 900
atcatctgtc aaaaaatgtg gtacttttat ctcatcggca ccggcaagat gcgcattacc 960
cccgacgcct tcgagatcca gcggagtcga cacgagacgg gcatttttac ttttattatg 1020
gaagattaca gaacgttcgc cggcacgctg tcccggcacc cgcaccgtcc gcacccacaa 1080
cagcagcagc accaccaccc cggtcccccc catcctcctc tttctcaccc tgcctcgtcc 1140
tgtctcagcc cagaggccgt actggccgcc cgcgcccttc atatgccgac gctggctaac 1200
gacgtgtga 1209
<210> 9
<211> 693
<212> PRT
<213> Artificial Sequence
<220>
<223> Chemically Synthesized
<400> 9
Met Pro Arg Val Asp Pro Asn Leu Arg Asn Arg Ala Arg Arg Pro Arg
1 5 10 15
Ala Arg Arg Gly Gly Gly Gly Gly Val Gly Ser Asn Ser Ser Arg His
20 25 30
Ser Gly Lys Cys Arg Arg Gln Arg Arg Ala Leu Ser Ala Pro Pro Leu
35 40 45
Thr Phe Leu Ala Thr Thr Thr Thr Thr Thr Met Met Gly Val Ala Ser
50 55 60
Thr Asp Asp Asp Ser Leu Leu Leu Lys Thr Pro Asp Glu Leu Asp Lys
65 70 75 80
Tyr Ser Gly Ser Pro Gln Thr Ile Leu Thr Leu Thr Asp Lys His Asp
85 90 95
Ile Arg Gln Pro Arg Val His Arg Gly Thr Tyr His Leu Ile Gln Leu
100 105 110
His Leu Asp Leu Arg Pro Glu Glu Leu Arg Asp Pro Phe Gln Ile Leu
115 120 125
Leu Ser Thr Pro Leu Gln Leu Gly Glu Ala Asn Asp Glu Ser Gln Thr
130 135 140
Ala Pro Ala Thr Leu Gln Glu Glu Glu Thr Ala Ala Ser His Glu Pro
145 150 155 160
Glu Lys Lys Lys Glu Lys Gln Glu Lys Lys Glu Glu Asp Glu Asp Asp
165 170 175
Arg Asn Asp Asp Arg Glu Arg Gly Ile Leu Cys Val Val Ser Asn Glu
180 185 190
Asp Ser Asp Val Arg Pro Ala Phe Ser Leu Phe Pro Ala Arg Pro Gly
195 200 205
Cys His Ile Leu Arg Ser Val Ile Asp Gln Gln Leu Thr Arg Met Ala
210 215 220
Ile Val Arg Leu Ser Leu Asn Leu Phe Ala Leu Arg Ile Ile Thr Pro
225 230 235 240
Leu Leu Lys Arg Leu Pro Leu Arg Arg Lys Ala Ala His His Thr Ala
245 250 255
Leu His Asp Cys Leu Ala Leu His Leu Pro Glu Leu Thr Phe Glu Pro
260 265 270
Thr Leu Asp Ile Asn Asn Val Thr Glu Asn Ala Ala Ser Val Ala Asp
275 280 285
Thr Ala Glu Ser Thr Asp Ala Asp Leu Thr Pro Thr Leu Thr Val Arg
290 295 300
Val Arg His Ala Leu Cys Trp His Arg Val Glu Gly Gly Ile Ser Gly
305 310 315 320
Pro Arg Gly Leu Thr Ser Arg Ile Ser Ala Arg Leu Ser Glu Thr Thr
325 330 335
Ala Lys Thr Leu Gly Pro Ser Val Phe Gly Arg Leu Glu Leu Asp Pro
340 345 350
Asn Glu Ser Pro Pro Asp Leu Thr Leu Ser Ser Leu Thr Leu Tyr Gln
355 360 365
Asp Gly Ile Leu Arg Phe Asn Val Thr Cys Asp Arg Thr Glu Ala Pro
370 375 380
Ala Asp Pro Val Ala Phe Arg Leu Arg Leu Arg Arg Glu Thr Val Arg
385 390 395 400
Arg Pro Phe Phe Ser Asp Ala Pro Leu Pro Tyr Phe Val Pro Pro Arg
405 410 415
Ser Gly Ala Ala Asp Glu Gly Leu Glu Val Arg Val Pro Tyr Glu Leu
420 425 430
Thr Leu Lys Asn Ser His Thr Leu Arg Ile Tyr Arg Arg Phe Tyr Gly
435 440 445
Pro Tyr Leu Gly Val Phe Val Pro His Asn Arg Gln Gly Leu Lys Met
450 455 460
Pro Val Thr Val Trp Leu Pro Arg Ser Trp Leu Glu Leu Thr Val Leu
465 470 475 480
Val Ser Asp Glu Asn Gly Ala Thr Phe Pro Arg Asp Ala Leu Leu Gly
485 490 495
Arg Leu Tyr Phe Ile Ser Ser Lys His Thr Leu Asn Arg Gly Cys Leu
500 505 510
Ser Ala Met Thr His Gln Val Lys Ser Thr Leu His Ser Arg Ser Thr
515 520 525
Ser His Ser Pro Ser Gln Gln Gln Leu Ser Val Leu Gly Ala Ser Ile
530 535 540
Ala Leu Glu Asp Leu Leu Pro Met Arg Leu Ala Ser Pro Glu Thr Glu
545 550 555 560
Pro Gln Asp Cys Lys Leu Thr Glu Asn Thr Thr Glu Lys Thr Ser Pro
565 570 575
Val Thr Leu Ala Met Val Cys Gly Asp Leu Gly Val Gln Val Glu Thr
580 585 590
Ile Ser Pro Gly Asp Gly Arg Thr Phe Pro Lys Arg Gly Gln Thr Cys
595 600 605
Val Val His Tyr Thr Gly Met Leu Gly Asp Gly Lys Lys Val Asp Ser
610 615 620
Ser Arg Asp Arg Asn Lys Pro Phe Lys Phe Met Leu Gly Lys Gln Glu
625 630 635 640
Val Ile Arg Gly Trp Glu Glu Gly Val Ala Gln Met Ser Val Gly Gln
645 650 655
Gly Ala Lys Leu Thr Ile Ser Pro Asp Tyr Ala Tyr Gly Ala Thr Gly
660 665 670
His Pro Gly Ile Ile Pro Pro His Ala Thr Leu Val Phe Asp Val Glu
675 680 685
Leu Leu Glu Leu Glu
690
<210> 10
<211> 107
<212> PRT
<213> Artificial Sequence
<220>
<223> Chemically Synthesized
<400> 10
Gly Val Gln Val Glu Thr Ile Ser Pro Gly Asp Gly Arg Thr Phe Pro
1 5 10 15
Lys Arg Gly Gln Thr Cys Val Val His Tyr Thr Gly Met Leu Glu Asp
20 25 30
Gly Lys Lys Phe Asp Ser Ser Arg Asp Arg Asn Lys Pro Phe Lys Phe
35 40 45
Met Leu Gly Lys Gln Glu Val Ile Arg Gly Trp Glu Glu Gly Val Ala
50 55 60
Gln Met Ser Val Gly Gln Arg Ala Lys Leu Thr Ile Ser Pro Asp Tyr
65 70 75 80
Ala Tyr Gly Ala Thr Gly His Pro Gly Ile Ile Pro Pro His Ala Thr
85 90 95
Leu Val Phe Asp Val Glu Leu Leu Lys Lys Glu
100 105
<210> 11
<211> 2082
<212> DNA
<213> Artificial Sequence
<220>
<223> Chemically Synthesized
<400> 11
atgccacgcg tcgaccccaa ccttcggaat cgggcccgcc ggccacgagc cagacgaggc 60
ggcggcggtg gcgttggcag caatagcagc cgacacagcg gaaaatgccg ccgccaacgc 120
cgagctctgt cggcgccgcc gctcactttc ctcgccacca ctaccaccac gaccatgatg 180
ggcgtcgcca gtaccgacga cgacagtctc ctcctgaaaa cgccggacga gctggacaag 240
tacagcggct cgccgcagac catcctcaca ctgacggata aacacgacat ccgtcagcct 300
cgggtgcacc gcggcaccta ccatctgatc cagttgcacc tcgacctccg acccgaagaa 360
ttgcgggatc ccttccagat tctgctctct acgccgctgc aattggggga agcgaacgac 420
gagtctcaaa ccgcccccgc gacgttgcaa gaagaagaaa cggcggcttc ccacgagccc 480
gagaaaaaaa aggaaaaaca agagaagaaa gaagaggacg aggatgaccg caacgacgat 540
cgtgaacgcg gcattctatg cgtggtctct aacgaggatt ctgacgtgcg cccggccttc 600
tctctctttc ccgcacgccc aggctgccat atcctgcgct cggtaattga ccaacaactg 660
acgcgcatgg ccatcgtgcg cctatcactc aatctcttcg cgctccgtat catcacgccg 720
ctgttgaaac ggctaccgct acgacgtaaa gccgcgcatc acacggcgtt acacgactgt 780
ctggcgctgc atctgccaga actcacgttc gagccgacgc tggatataaa caacgtaacg 840
gagaacgcgg cttccgtcgc tgataccgcg gaatcaacgg acgcggatct gacgcccacg 900
ctgacggtgc gcgtacgaca cgcgctgtgc tggcatcgag tggaaggcgg catctcgggg 960
ccgcgtggac tcaccagccg tatctcggcg cgcctctcgg aaaccacggc caagacattg 1020
ggaccctccg tctttggacg attggagcta gacccgaacg aatcaccgcc ggacctgacg 1080
ctgtcgtcac tcacgctata ccaagacggc atattacgtt tcaacgtgac ctgcgaccgc 1140
accgaggcgc cagccgaccc agtggcgttt cgcctgcggc tgcgacgcga aacggtgcga 1200
cgacccttct tttcggacgc gccactgcct tactttgtac cgccacgctc cggcgcggcg 1260
gacgagggac tggaggtgcg cgtcccttac gaattgacgc tgaagaactc gcacacgtta 1320
cgtatctacc gccgctttta cgggccttat ctgggtgttt ttgtaccaca caaccgtcag 1380
ggactcaaaa tgcccgttac ggtctggcta ccgcgctcct ggttggaatt aaccgtactg 1440
gtgagcgacg agaacggcgc cacgttccca cgggacgcgc tcctggggcg cctctatttt 1500
atctcgtcaa agcatacgct gaatcggggt tgcctgtcag caatgacgca ccaagtcaaa 1560
tccacgctac actcgcggtc cacatcccat tcgccgtcgc aacagcagct ctcggtgctg 1620
ggcgcttcca tcgcgctgga ggacctgctg cccatgcgac tggcgtcccc ggagacggaa 1680
ccgcaagact gtaagcttac ggaaaatacg acagagaaga cgagtcctgt cactttagcc 1740
atggtctgcg gcgatctcgg agtgcaggtg gaaaccatct ccccaggaga cgggcgcacc 1800
ttccccaagc gcggccagac ctgcgtggtg cactacaccg ggatgcttgg agatggaaag 1860
aaagttgact cctcccggga cagaaacaag ccctttaagt ttatgctagg caagcaggag 1920
gtgatccgag gctgggaaga aggggttgcc cagatgagtg tgggtcaggg agccaaactg 1980
actatatctc cagattatgc ctatggtgcc actgggcacc caggcatcat cccaccacat 2040
gccactctcg tcttcgatgt ggagcttcta gaactggaat aa 2082
<210> 12
<211> 107
<212> PRT
<213> Artificial Sequence
<220>
<223> Chemically Synthesized
<400> 12
Gly Val Gln Val Glu Thr Ile Ser Pro Gly Asp Gly Arg Thr Phe Pro
1 5 10 15
Lys Arg Gly Gln Thr Cys Val Val His Tyr Thr Gly Met Leu Glu Asp
20 25 30
Gly Lys Lys Val Asp Ser Ser Arg Asp Arg Asn Lys Pro Phe Lys Phe
35 40 45
Met Leu Gly Lys Gln Glu Val Ile Arg Gly Trp Glu Glu Gly Val Ala
50 55 60
Gln Met Ser Val Gly Gln Arg Ala Lys Leu Thr Ile Ser Pro Asp Tyr
65 70 75 80
Ala Tyr Gly Ala Thr Gly His Pro Gly Ile Ile Pro Pro His Ala Thr
85 90 95
Leu Val Phe Asp Val Glu Leu Leu Lys Pro Glu
100 105
<210> 13
<211> 321
<212> DNA
<213> Artificial Sequence
<220>
<223> Chemically Synthesized
<400> 13
ggagtgcagg tggaaaccat ctccccagga gacgggcgca ccttccccaa gcgcggccag 60
acctgtgtgg tgcactacac cgggatgctt gaagatggaa agaaagtcga ttcctcccgg 120
gacagaaaca agccctttaa gtttatgcta ggcaagcagg aggtgatccg aggctgggaa 180
gaaggggttg cccagatgag tgtgggtcag agagccaaac tgactatatc tccagattat 240
gcctatggtg ccactgggca cccaggcatc atcccaccac atgccactct cgtcttcgat 300
gtggagcttc taaaaccgga a 321
<210> 14
<211> 230966
<212> DNA
<213> Artificial Sequence
<220>
<223> Chemically Synthesized
<400> 14
gggccgcgtg gtgggtcctc gaggggcggg ggggtgtttt tagcgggggg gtgaaacttg 60
gagttgcgtg tgtggacggc gactagttgc gtgtggtgcg gaggacggcg acggcgaata 120
aaagcgacgt gcggcgcgca cggcgaaaag aagacgcgtg tctgtgtctg tgtgattccc 180
cggggaaaag aggaagttcc cgggggacgg cagcatgggt ccctggggac acacgaaaag 240
caacgcccgg gggcgaggga cgacggccct ggggaccgcg ggggaaataa cggccgcgag 300
gccacacact cgttcctgcg aagccgcaca ccccgaggcc gcgcacaccg ccgacacacc 360
ccgccaccac accccgccgg cacacccgcc acacgcccgc gacacacccg gcacgacaca 420
cccggcacac gcccgcgaca caccctgaca caccctgcca acacaccccc gacacaccca 480
acacacgccc gcgacacacc cggcacacac ccacccggcc gcgccccgac acacccaaaa 540
caccgccggt gcggggccgc gtggtgggtc ctcgagggag tgttgagggc cgtaagcgtg 600
ttgtgtccga cgctgcctgc gcactgccgg tgcgtgtcgt cccacggtat ttgttgtcgg 660
caccgggctt cgggacggtg tttcggcgcg ctgccggtgc gttccacggt ccttgcctgt 720
gtcgtttcgg cgctgcgctt gtcgggggtt ttcgagcgtt ctggccgccg gcgatgccgg 780
ggtgttgcgg agacgggggg tgtgcgggac ggtgttgggg ccggggacgg gggttgcgct 840
ggggccgggg ctgttcgcgc cgcgtagggg aggttacgtt ggggacgggg acagtttgcg 900
gcgcggacca gggaacccac ctcacctatt taacctccac ccactacaac acacacatgc 960
cgcacaatca tgccagccac agacacaaac agcacccaca ccacgccgct tcacccagac 1020
gcccaacaca cgttaccctt acaccacagc aacacacaac cgcatgtcca aacctcggac 1080
aaacacgccg acgaagaaca ccgcacacag atggagctcg acgccgcaga ctacgctgct 1140
tgcgcacagg cccgccaaca cctctacgat caaacacaac ccctactact cgcatacccc 1200
aacaccaacc cacaggacag cgctcatttt cccacagaga atcaacatca actcacgcat 1260
ccacttcaca acattggcga gggcgcagca ctcggctacc ccgtcccccg cgcggaaatc 1320
cgccgcggcg gtggcgactg ggccgacagc gcaagcgact ttgacgccga ctgctggtgc 1380
atgtggggac gcttcggaac catgggccgc caacctgtcg tcaccttact gttggcgcgc 1440
caacgcgacg gcctcgctga ctggaacgtc gtacgctgcc gcggcacagg ctttcgcgca 1500
cacgattccg aggacggcgt ctctgtctgg cgtcagcacc tggttttttt actcggaggc 1560
cacggccgcc gtgtacagtt agaacgtcca tccgcgggag aagcccaagc tcgaggcctc 1620
ttgccacgca tccggatcac ccccatctcc acatctccac gtcggaaacc gccgcacccc 1680
gccacatcca ccgcatcgca ccacccacat gcttcgcctc ggtcagatca cacgcttttt 1740
cctgtcccat ctacaccctc agccacggtt cacaatcccc gaaactacgc cgtccaactt 1800
cacgccgaaa cgacccgcac atggcgctgg gcacaacgcg gtgaacgtgg cgcgtggatg 1860
ccggccgaga catttacgtg tccaaaggat aaacgtccct ggtagacggg gtagggggat 1920
ctaccagccc agggatcgcg tctttcgccg ccacgctgct tcaccgatat ccaataaacc 1980
catcccctcg ccacgacgtc tccgcgtatc tttgtagcct caagaatccg tccccacgtc 2040
cacccatccc gagcactcca cacgccataa caaaccacgg acacgacaaa tgcatgcaaa 2100
cttctcattt attgtgtcta ctactctgtg ttgctacagg gagtgaagag ggtgaaggca 2160
aagaaaaaaa aaaggaacaa aataatagat tagcagaagg aataatccgt gcgaccgagc 2220
ttgtgcttct tttcttataa ggaggcaaat atactaggga aaacataaga ataggaagaa 2280
accgaggttt gggagaaaag ctgagataaa atagcgcatt ttccatacag aggttgttgt 2340
ttttgtggat cctaagaggt ttcaagtgcg aatctcaaag ttctcacgag aatattgtct 2400
tcaagtatcg acaactgtgg tccaagattt ttttttggtc tttttaggtt ctgcgaggga 2460
catcacgatg gatcgttgcg atgaagtcac gcgtacgcct ctggtgtggc gcggtgtcgt 2520
gacaggagag tgtgttttca gtgcagagct gtcttgattc ctatatccga gtatctgttt 2580
tctcgtaagg acggtaatct tctttggtgt aagtacatct aaaagctgca aactatattt 2640
taagggctgt ctctaggtgt actttgatgc tggagttttt cgctgtgttg atgtgaataa 2700
atctactact actattatat gcagaaagag tgattatgcc gagacaagat tgcattggct 2760
gaactgtttc aaaaacgcct acactctact tatccgtaaa cctaaggtaa tactatgtgt 2820
aagttgtttt tttttctttt tgtagtaaaa tggtgatacg tgcaattaaa actgtattcc 2880
atgtttccat cctttcattt caactttaaa ggcggctttg agagcgaaga agtgcgagga 2940
taaaaatgga tgactccttc gtgtccaggg agtcgactac tgcaacgctg attgattaaa 3000
agatggtctc cgatgatgat gttgttattg atcgaatcat ggtgcagaac ggcgacggag 3060
aggagcgtgt ccgccgccgg gaaggtggtc tctttctctt ttcttttttc aagaaatctt 3120
ccatgtgttt atcgtagtga tcgaaatcga ctgatctcgg gttctttttg ttggtttctt 3180
ttcggttaat catgtattgt tttctttttt tacagaaaga tacttttttt catgagcaat 3240
tcctcgcccg gcgccggcat gccgaggtgg ggccactgcg atcagcggca tgccgacgcc 3300
gacccgggga tcttggattc accgttttct ctcttctctc tctacataca gaccgggtgg 3360
caggagcggt aaggaatcat cgtcgtcttt cattcttcga tgattatggt aatactaaat 3420
cttatctagg agcatataca tctaagattg gagtactagt agtcgtttgt ggtttctatt 3480
tttttttata tttatctatg acagtttttc tgtttttcgt tttgataata atataataaa 3540
aactcatgga cgtgaaatct ggcttggttg tggtgatttc attctcatta ttgttgtttt 3600
ctttccgtct tgcggatgaa gatgttgcga tgcggttgtt gttggtgttg ctatacaccg 3660
agagagatga tctttttgtt cttctggttc atttcctatg attgtttggc tgctgaccga 3720
cgcgtcagga tgtgcagggc atgcggggaa tcaggaccgg acacgggata atttcatcta 3780
cctatacgga gatcgcggtc ctcgccatga ggatcgcgac aggcgcgtcg agggggcagg 3840
aacacccttg cggattgaca ttcttggtgg tgtttcgttg ttgtcggtag ttgttgttga 3900
cgatgaggat aaataaaaat gaccttgttt ttgttctgtt ttctcttgtt gggaatcgtc 3960
gactttgaat tcttcgagtt atcggaaagc tgaggtaccc aaatgtctgt agcttttttc 4020
tttttaccct cttgtttatc atctgcgatt cgtggtaggt aggagaggga aatgataatc 4080
cgagattaag gaaaggagaa gataaaaaat aaaaaaaaat aataaaacag aagccgaccg 4140
gccgccgacc cgttccccag gaccagccta cgaggaacgg ataacgcggt ggcgacggca 4200
gcggtggtgg cgctgggggt ggcggcagtg gtactgctga tggtagtcgg gacggaggag 4260
aggcgatgca tacatacacg cgtgcatgct gcatgggtgg atggtacggc cgggagacgc 4320
ggaagagaaa ctcacataaa aaggtgacaa aaagagcggt tgaaaaaaga aaacaagatt 4380
cgaccagaca gaagagaagg accggggctt ggcgaccctt ccacgactgc tgttgtcatc 4440
tcggctcctc cgtcttctcc cggccacggg cggctaagtc accgccgttc tccccatccg 4500
tccgagcgcc gaccgaccag ccggccgatt cgcccgccgg ggcttctgga gaacgccggg 4560
gcagcagcga tctggggaag ctgctaaacc cctgcgtttt tatatggtag ctctgccgag 4620
cgcgggctga cgcgttgggt aagcggaaag acgtgtgtga cgaaaagggg tcccatggta 4680
tttcacgtga cgatgaggag atacggtttg gagcacatac ggtttagaaa aagggagttg 4740
tcgtgacaag ggctgaggga cctctgtctc catgtgtgta taaaaagcaa ggcacgttca 4800
taatgtaaaa aagaacacgt tgtaaacaag ctattgctgt atcattcggc tgactatgct 4860
tcattcggac tgattttctt ttcctaacgg cgtaacttaa agtgattaac gtatgatatt 4920
tgttccccag agttatacta tagtcatcat cctaaaattc agatataaat gaacacatgt 4980
cgtatgggat tattaagaaa ccgaaactct ccacagttca ccatcttctt cgtcattcaa 5040
ccgatgaccc actccgtaca acgaatcagt ctgctgcgtc atattgcaaa gcacaagcga 5100
cgtatgcgaa caacttgaaa cacaggctgt tgtattgacg accgttgtac cattattagt 5160
caccaccgtt atcccatgtt tcccacccga tggaaaaccg tcttctatca tcaactgtgg 5220
taagatttcg accctgcgag gtattcagtt tcctcatatc cataacctgg attttatcat 5280
taaaccccaa tattaaacac ttttttagta ccccccaccc accaaaaaat gtgactggac 5340
cggttcctag cagctctggg agccatgttc aggttgaacc acagctacag cgaaaccgag 5400
tccagtgacc ggtaaccacg tccagcccct gcgtatgtac cagtccaagc acgtccggtc 5460
attgttctac acaggaaatc taactaggtc aacgcaattt tattccaccg ttacgcagaa 5520
tactaacaaa aaaacacaca aatttaacga attacacgta gtttattaca tgaaaactgt 5580
aagaacacca attcactaag cgatacaaca tttagctgac ttccaagtgc cacacatcac 5640
cactgtattc atccatgttt tcaccgaacc aacgagacag atcgaagaag ccagaatctc 5700
ccgactttaa attacataaa tccaacgtat tatgaccaca gctcgacaca caaatagttg 5760
cgttactatt cacagtagca ttacctatac ccgtaacgtt gcacaaccac tgatcaccat 5820
tgttaccaaa aacggttttc cacttagttg tcaacggatc tttcctatgc gtaatggtaa 5880
aattactacc agtcgtcgct tttagctcat tacgagtatt atccgcatcc acatatatca 5940
acgtcatagc taggcacgct ataagtaccc cccccccaca atggaatgtt gccaaaccgg 6000
ttctttcccg ttatagccat agcgttccca ggcaaaagca aacgccaaac ctaatgcagt 6060
gaaaagcgct tgcagccaga accagcttat gtaccagcca caatcacatc cggttattgt 6120
ttccacagga aatcctacca ggcaaagccc cgcttgtttt gttcctatct tgtttagcaa 6180
ttcgtaaact gtcagcctag cgacgtccgt ttagatcaaa agtcacgtat atagcgacgc 6240
tgtttccatc cgtttccccg tcccgccgtt tccgaacaac ccacccgggt tcagacaacc 6300
gaccaccaac agaaatatac acacagacca ctgggagttc agttaaagat ttcatcaggt 6360
ttattttggc tgctgctagt cttttgcttc ttagaaaaaa aatacccata tagagaaata 6420
atgatagttt gacaacacat atggcaggga tttcttcttc atcaataaga tatgcaattc 6480
ccccagggag agactttcaa caattgaatt tacaaaaaca aaattacatc aggagaaaga 6540
gaggatacat taataaatat attatatctg gtgtatatac tgaatgctgc tggttcataa 6600
ggtaacgatg ctactttttt taattccaag atggtttttc tttgttagtc ttttgttgac 6660
ttgctggttc ctaaaagttc gcaaaaacga ttgtgtgaag attttatgac gttggttgac 6720
tagttcatga gattctgctg tacgtgtgat ggttattcgc tggttcgttc taagatgagt 6780
atcgtactgt gtctgcgatg gtcgtctctt actggcattc tctcggctgc ctcttgcttt 6840
catgattgaa aaggaaaaaa ggactccgag ggcgcggtca tcttttactt ttcggttttc 6900
tcgttggcgg gtcagaggta gtcagatcat gagactgtcg tggtcgatga aactgtgtct 6960
gctcaagtga cgtccatttc ttgtacggag aaaaaagtca tcgggataaa taaggctata 7020
caaggcgttg tcaagcgtgc ggctctaaac aaattaagcg atacaaaatt acagtaatac 7080
gaataataaa ttacccccct ccccctgtgg tcccccgaga cgagagccac ccatcgtgta 7140
ctctcgcacc acccacgacc acagagggag acgggacgaa gagacgacgc acagcgccat 7200
ctcctcctgg aggccggcga cgttaactgc tacagctgcg gcggcgaaga cagctgcgat 7260
ttgtcggccg acatgccgat ggtatgggcg gcggcggcaa tggccgcggc agcggggagg 7320
agaggagaga gaagaggagc ggggcgtccg aaggcgagga tggcatggtc tcgccggagc 7380
gcccggcttt tatggaacac tcgcgtccgg ttgggtatca cccacaggaa gatgagtcac 7440
aacttccaaa ccatcttgag acccgagtaa cggtttacag gtcgcacgcc agtcagctaa 7500
aaacagcgga cagtcccacg ctgtttctgt tgtggctctc tccagtttcc tcatcaccgt 7560
cccggtctcc gtcgtcatcg gaagaatacc acccgctctc atgcggcagt cgatcggcct 7620
cgacgaacga gacgcggcga cgcctctcca cggccgactg gttgtggtgg tgaaagaaga 7680
gcaccagcaa tcccaggagg agcaacaagc cctcacatgt ccaggaggtc ggggagaggg 7740
cctgtcggag atggccgtga ggcatcacgt acggcagctg aggagaaacg gagaagaaag 7800
gaaaattacc gtcaggggcc ggggttctta ttagagaaac agcacgtagg tcaggatcca 7860
gatgctaatg gcaatcatga tgacgatgat catgcaggcc aagacgcggc gcaccaatgc 7920
cgaatccaat agccgccgtg cctccggttg gtggccggcg gcatctagag acatgatttg 7980
ggggggaccg gcggcgcaaa aagacaggga gatggacagt gtcacggtgt tttgttataa 8040
ttaggacatg gggaccggaa gccgagacag agtactacag ggtgttgaag ggtaacgtga 8100
gggagatcat gtcatgggcg ggctgaagac cgtgcgggga ggattgacgt gtgcggtgct 8160
tgtggaacac ggtgttttaa tatgtatccg cgtgtaatgc acgcggtgtg ctttctggca 8220
ctcagcttgg taagctatgt ggccgtctgc gccgaaacca aagtcgccac caactgtctc 8280
gtgaaatcag aagataccca tttgacgtgc aagtgcagtc cgaataacac atcatctaat 8340
accggcaatg gcagcaagtg ccacgcgatg tgcaaatgcc ggatcacaga acccattacc 8400
atgctaggcg catactcggc ctggggcgcg ggctcgttcg tggctacgct gatagtcctg 8460
ctggtggtct tctttgtaat ttacgcgcgc gaggaggaga aaaacaacac gggcaccgag 8520
gtagatcaat gtctggccta tcggagcctg acacgcaaaa agctggaaca acacgcggct 8580
aaaaagcaga acatctacga acggattcca taccgaccct ccagacagaa agataactcc 8640
ccgttgatcg aaccgacggg cacagacgac gaagaggacg aggacgacaa cgtctgataa 8700
ggaaggcgag aacgtgtttt gcaccatgca gacctacagc acccccctca cgcttgtcat 8760
agtcacgtcg ctgtttttgt tcacaactca gggaagttca tcgaacgccg tcgaaccaac 8820
caaaaaaccc ctaaagctcg ccaactaccg tgccacctgc gaggaccgta cacgcacgct 8880
ggttaccagg cttaacacta gccatcacag cgtagtctgg cagcgttatg atatctacag 8940
cagatacatg cgtcgtatgc cgccactttg tatcattaca gacgcctata aagaaaccac 9000
gcgtcagggc ggtgcggcgt tcgcgtgcac gcgccaaaat ctgacgctgt acaatctcac 9060
ggttaaagat acgggagtct acctcctgca ggatcagtat accggcgatg tcgaggcttt 9120
ctacctcatc atccacccac gtagcttctg ccgagccttg gaaacgcgtc gatgctttta 9180
tccgggacca gggagagttg tggttacgga ttcccaagag gcagaccggg caattatctc 9240
ggatttaaaa cgccagtggt ccggcctctc actccattgc gcctgggttt cgggaatgat 9300
gatctttgtt ggcgcgctgg tcatctgctt cctgcgatcg caacgaatcg gggaacagga 9360
cgctgaacat ctgcggacgg acctagatac ggaacctttg ttgttgacgg tggacgggga 9420
tttacagtaa aagatgcgtg tcgcctgccg aagacctcac catctcacgt acaggcatac 9480
ggcgtataca atcataatat tctatattct gcatagagtt acatgcaaca gtactactac 9540
caatactgca tccatcacat cacccaacac tgcttctacc acctttgtga ccagcgtatt 9600
ttctactccg aataacaaca catcaacgac gccacacaca tctgtcacct cacaagcgtc 9660
aaccattggc aacatcacca acgttacctc cgacttgagt actttcacaa ccgtatattc 9720
tacattcaat acatcatatg ctaatatatc caatacggct gccactacag aattgatttc 9780
aacaaatacc aacactatat tatcttttac caacgtaaca gcaaacgcta catcatctta 9840
taacacaaca atcaccgtaa ctatcacgtc agatgaaact tcgcacaacg tatccactaa 9900
tactgcactt ataagcacgc catggcttac aaattgcagc gccacaacgt acaccacgta 9960
caaccgtact aactcttcca acgcttgtca cacagagaca acaatcatac gtttcaaaga 10020
aactaataca acaggaatag aagggagtaa tgtcaccata aaaggtaatt ctacgtggga 10080
ttgtctttca gtcgcctgga tacgacatta caatcgatcc acacacggac atcatctagg 10140
tcatcgtaag aacgcacata cccaatcttg gtattggtta cgcatcctta cctctcatac 10200
tgtatgtcat tctcaacatg aaagaccttc actgtaccat gacttatgtc gttcgtgcaa 10260
caacacagaa ctacatctgt acgatctaaa tatcaccaat tccggcaggt acagcagacg 10320
ttgttttaaa gaaaattact tcacaggaca tcacgaagat gaaaatttct acctattagt 10380
aacaccaaaa aatcatactg aagctattaa tgctactttc gtttgcccta gatacaacac 10440
cgatatcgaa aatgaagata gagagaaagg aagtcaacat actaacaata cacatcacca 10500
caaacgtaat ctctatcata gctcgcaaag aagccgcacc gtatggacca tcgtgttggt 10560
ttgtatggcc tgcatagttc tgttttttgc acgacgagcc tttaacaaaa agtaccatat 10620
gttgcaagac accgtcagtg aatcagaatt cattgttcga tatcacacag aacatgaaga 10680
ttgagctacg tttccgggca gacatcttat gaagctgaac aataaactaa aacattctgt 10740
aaggctcagc gttcaaagga atattaatgc ccattgagcg agaactaata ttgcaatgga 10800
ctggcgattt acggttatgt ggacgatact aatatccgcg ttatcagaaa gctgcaatca 10860
aacctgttcc tgtcaatgtc cctgtagtac taccgttaac tattccacta gtactgagac 10920
agccacatca acatacagta caacagttat cagcaataaa agcacttcag aatctataaa 10980
ttgctctact gcaactgcac cagcaaccac cgtttctaca aaaccgtcga aaacaaccac 11040
acagatatcc acaacgacaa atacaaacgt tgagactacc acatgtacca acaccaccac 11100
gaccgttact tgtgatggtt tcaattatac agtccataaa agatgcgacc gcagttacga 11160
ggtaatcaac gtaacaggat acgttggtgg caacataact ctaaaaaatg caatcagact 11220
gagaaatggc acaatgtaga ctggattcat tatgagtacc ccacgcataa aatgtgcgaa 11280
ttaggcaact atcaccaaac aacaccacgg cacgacatat gttttgactg caacgacacc 11340
tccctaacta tctacaactt aaccacaaga aacgctggaa aatataccag gcatcaccgt 11400
gataacggtc aagaagaaaa ttactacgta acggtgttaa ttggagacac aacgttatcc 11460
actcttggca catgccctgt aagatataaa gaatctagga acactgaaaa caccattgga 11520
agtaacatca taaaaaccat tgagaaagct aacattcccc tgggaattca tgctgtatgg 11580
gcaggcgtag tggtatcagt ggcgcttata gcgttgtaca tgggtagcca tcgcattccc 11640
aaaaaaccgc attacaccaa acttcccaaa tatgatccag atgaattttg gactaaggct 11700
taacatgcac atcaataaac tttttttaac caataacatg tctctgtttt tttttgttaa 11760
caacctatga tataaagcgg tatattcaat cattactaaa caaaaaaaca tgggcatgca 11820
atgcaacact aaattgttat tgccagtcgc actaataccg gttgtaatca tcctaattgg 11880
tactctagtg cccatacttt tacatgaaca aaaaaaggcg ttttactggc gactttttct 11940
gcaaagtcaa catgtagaag cacccattac agtaacgcag ggagacacag tctacctaga 12000
tgctagcaat aatccctgta attattccag cttttggtac cacggtaatt gcgaactttg 12060
tggatggaac ggatatctac gcaatgttac acattactac acaaacacat cgtgttcccc 12120
gcaattcatg tgcataaacg aaactaaagg tctgcagtta tataatgtaa cattaaacga 12180
ttcaggtgct tatactgaac acgtttacga atgtgatctt tcatgtaaca ttactactta 12240
taacgaatat gaaatactca attacttcga taactgtaac tacaccataa atagcaccaa 12300
gcatattatc accgtggtgt cttcacgtca ttctaaacaa acaaattccc acgtatccac 12360
tcacgctggt tgggcagccg ccgtggtgac ggtaattatg atctacgttt tgatccactt 12420
taacgttccg gcaactctga gacacaaact acgaactaga aacaacgtaa atcgcatagc 12480
gtgattacaa agtatcgaca ctaatttatc caagataaaa tttgattact ccgtgcggtt 12540
ctcaaaaact gtaaggtccc gcttttctac tccatcatga aggatcgcaa tagaatactg 12600
ctatgtatca tctttatttg catcatgtgc ctcatttgta tttactttaa acgtcgttgt 12660
gttcttactc cgtctccaga caaagcggat ctgcgagtgg aatttccctc gttacccccg 12720
tgtatcggca tacaatgtgc tgcatgagaa cacgcgtgac acatagcgta cccctggacg 12780
gtacagttta tgataacgtc attcagggga agtatacatt actatcgacg tgttatcaca 12840
gaacacacag attttctgcg tgttttataa aagagcgtct cgaagcagct tgagccacac 12900
tacggtccag atgacgagcg taatcaaaaa tatgccgcgc agtagtcgaa agccgtactg 12960
agcgtgcgag gcgggtaggg tgccgaacga cggatatgcg tcgttgtcat cttcgactat 13020
aaggatcgcg accgagtctt cggccatggt aaacgtcacc ctgtgtggct ggtatgtagc 13080
gtatccggtt tggaattgtt ctgctccagc tcgggggata gtgaggaatt ctcaagggat 13140
acgggaccca atgactggat aagagaaggg tttttccccg taagatgatc ctcgtatcac 13200
atgaggtctg gatatgtata aatgaagagt gaaataggca cagggaatca gatgccagcc 13260
tcgtgatgca gccgctggtt ctctcggcga agaaattgtc gtctctgttg gcttgcaaat 13320
acatcccacc ttaagcgatg agtccataaa gcaccgttgt ccgggtacgg tgaaagtgac 13380
tcggattgta gcacgtccct tttttttgtt tttgtatcgc ttatcgccac tgacagtgca 13440
atattttgat cgtgaggctg agtatggtta tgatgcttag aacgtggaga ttattaccaa 13500
tggtactact tgccgcgtac tgttattgtg tttttgggac ttgttcaatc ggcacgacga 13560
ctgctcccgt ggaatggaag tctcccgacc gtcagattcc taagaatatt acttgcgcta 13620
actactcagg gaccatcaac ggcaacgtta catttcgagg tcttcagaac aaaacggaag 13680
actttttgca ctggttgtta gggtggggtc ataagtccat ctgttcgttc ttcccgaaac 13740
tccagggcaa ctataacgaa caacattaca gatatgaagt agcgaacctg acgtataact 13800
gcacctataa ccgcttgacg ttgctaaatc tgacgacgga aaacagcgga aagtactatt 13860
ttaaaaggga agatgcgaat ttcacctttt attactcttg ttacaacctg accgtgtcct 13920
aaagaacgca cgtgaagttc cacagagccg cgtggctgta gctattgtgt ttacgttgct 13980
tttgaaatgt taagcgtccc tacggcgcta acatgtttct aggctactct gactgtgtag 14040
atcccggcct tgctgtgtat cgtgtatcta gatcacgctt aaagctcgtg ttgtcttttg 14100
tgtggttggt cggtttgcgt ctccatgatt gtgccgcgtt cgagtcctgc tgttacgaca 14160
tcaccgaggc ggagagtaac aaggctatat caagggacaa agcagcattc acctccagcg 14220
tgagcacccg tacaccgtcc ctggcgatcg cgcctcctcc tgatcgatcg atgctgttgt 14280
cgcgggagga agaactcgtt ccgtggagtc gtctcatcat cactaagcag ttctacggag 14340
gcctgatttt ccacaccacc tgggtcaccg gcttcgtctt actaggactt ttgacgcttt 14400
tcgccagcct gtttcgcgta ccgcaatcca tctgtcgttt ctgcatagac cgtctccggg 14460
acatcgcccg tcctctgaaa taccgctatc aacgtctcgt cgctaccgtg tagctagtta 14520
gccagctgtg tatagtttgt tgtgttttgc ttttgcatat ttgttttcag tcagagagtc 14580
tgaaacgggg tgggagggac ttttacgggt aatgcatgct aagatgaacg ggtgggctgg 14640
ggtgcgcttg gtaactcact gtttgaatac gcgctcacgc acatatgtag cactcaacat 14700
gttagctttt gcccgcacgc cccggggcgt gccgagctgc ctttttaata aagtctgggt 14760
ttccagatac gcgctggttc tgattttgat ggtttgtgcc tctgaaagct ctacgagctg 14820
ggccgtgaca tccaatcgac tgcctaactg tagcacgata actacaacag cgggtcaaga 14880
cgctgaattg cacggtccgg caccgttaag ctgtaatgtg acccagtggg gacgttacga 14940
gaatggaagc acacccgtat tatggtgcac tttatgggga tcacgcacgc gagtctcatt 15000
aggacaccgt gtagcgtttg gctgttcttg gaaaacattt tttatttata acgtttctga 15060
aagtagtggt ggcacttatt atcaaaaagg ttacaactgc accgacaaac atataacact 15120
atcttgtttc aacctaacgg tggttcctcg agcggttcaa agcacaacca ccgtaatgac 15180
acccacggtg gttacaaact ccacattcag tgtgtcactt gttgcgtcga gactgacgac 15240
aaattccagc gcgtttagac acgctagtta tcaacggcaa cagcgtgtcg gaaacgggac 15300
gttatccaag aacataacta acttggcatt cacctacggc agctggggcg tcgcgatgct 15360
gctgttcgcc gccgtgatgg tgctcgttga tttgggtttg cctcaatcgg cttggcgacg 15420
ctggcgaagc cacgtggacg atgaagaacg tggtttgtta atgtaggaaa taaaaggcac 15480
tgtttgagca tgactgtttc caaaccgtaa cgtggtaaat aaatcatggc ttccgacgtg 15540
agctcccatc ttctaacggt tacacaatcc cgttggacaa tacatcatat gtacaataaa 15600
ctgttgattt tggcgttgtt tacccccgtg attctggaat ccatcatcta cgtgtctggg 15660
ccacagggag ggaacgttac cctggtatcc aacttcactt caaacatcag cgcacggtgg 15720
tttcgctggg acggcaacga tagtcatctc atttgctttt acaaacgtgg agagggtctt 15780
tctacgccct atgtgggttt aagcctaagt tgtgcggcta accagatcac tatcttcaac 15840
ctcacgttaa acgactccgg tcgttacgga gcagaaggtt ttacgagaag cggcgaaaat 15900
gaaacgttcc tgtggtataa tttgaccgtg aaaccgaaac ctttggaaac tactacagct 15960
agtaacgtaa caaccatcgt cacgacgaca ccaacggtga tcggcacgaa aagtaacgtt 16020
acggggaacg ccagtttagc accacaacta cgtgccgtcg ctggattctt aaatcagacg 16080
cctcgggaaa acaacacgca cctggccttg gtaggtgtta tcgtatttat agctctaata 16140
gttgtttgta ttatgggatg gtggaagttg ttatgtagta aaccaaagtt atagtgatgt 16200
gctttttatc agggagaagg ttttgtgcca acaatgacta accctgggct atatgcatcg 16260
gaaaattata acggaaatta tgaacttacg gaagccgcca atacagcacg tacaaatagc 16320
agtgactggg taacgttagg aaccagtgcg tcgctgttga gaagcacgga gactgcggtt 16380
aaccctagca acgcgactac ggttactcca caacctgtgg aatacccagc tggggaagta 16440
caatatcaaa gaacgaaaac acattattct tggatgctaa ttattgccat aattctcatc 16500
atttttatta tcatctgtct gcgagcacct caaaaagtct acgatcgctg gaaagacaat 16560
aaacagtacg gacaagtatt tatgacggac acggagctgt gatgaactac aatgtataga 16620
tacacgtggc tgctttggtg gataacaata ttgcttcgta tacaacagtt ctatcaatgg 16680
tggaaaccag atacaacgtc atgcattcag aaaacgggat atgaaggtca aaacctcagt 16740
ctgcctccta gtaatgcatt atcatctaaa gactatactt tttcatggta taaagattca 16800
cttaaagccc ttaacatgtt atgttattat actgaaaaac ttgaagaaat agatagcaag 16860
ccagatacta tacgacgatg ttttttgaat catacattgt ttcttattaa tttaacaagt 16920
cactatagcg ggatttacta cttcgattct ctatacacat atggttgggt attacggaca 16980
cctctatgtt acaatgtcac tgtatattcc atatatcaaa cacacatcca cacaactata 17040
ttgctctatc cgcctacgtc cacatataat tcattaacta tatcatcatt tacctcaacc 17100
aacttaacac ataccgcggt ccactatgcc gccggtaacg ttgaagcaca acacgatact 17160
gccaccccac atacaatgtg gatcataccc ttagttatcg ttacaacaat tatcgtttta 17220
atttgtttca aatttcccca gaaagcttgg aataaattca cacaataccg atacaacagt 17280
atgctcaccg ccgcttaaag aatcaccgtc gagaaaacta aaacgtaaaa agaatggcca 17340
tgtacgttta tttttcagct cactgtttga ataccgtaaa cataatgacg tacatatacg 17400
tgattataca acaggtgttt gtgttatgcg gcgactgatt aaccatatcg tgaaccatga 17460
tcttttccga tggtccgtca tgaccgcaat gatattttac aggtattccg aaacctgtat 17520
ggaggtcact gtcagagtag gtgatccagt taccctcggt agtggacatg gttatcatcc 17580
aggacaaaaa gtacactggt ataaccagtc atgcgtcggc attagcaacg gcgaaaatac 17640
gcatcctatc tgcacctacg accctcctaa acctggtaga cgaaagacaa tgaaaaccac 17700
tccgttacca tcaccactgt tgtacgagtg tcacaattcc acattaagca ttcttcatgt 17760
aaacgtctca gatcccaaaa actattgcag gcgaaaatgt ccaccaaacg gtaactgtga 17820
atttcccaca tgttttacgt tatcactgat ttccagaacg acaaccacca gaaaacccgg 17880
acaaaaaact acgttgtcgc gattaaaaac cacgccaaat aaacatacgc agcacaaaag 17940
atccacgcga agaacgtcac ctagagatta caatgtaacg ggtctgccga aaggctttgc 18000
ggactcgttt accggtaacg tagaggcaca tagagccaaa gatgccgcac acagcgcatg 18060
gatcctcatt gtcatcatca ttatcatagt cgtcatttta tttttcttca agattcctca 18120
aagactcaga gagaaatggg acaccagagg atacctttac aaaggaaccg acggcctgcc 18180
cactacggac tacttatcgt gagcggacgg atatctccgg tttcaaaccc actgtttgaa 18240
tatagggaca gtccctacgg aacctgagaa catgtggaaa tcacctgtgg tagaatgctg 18300
ctcaggtaca ttacctttca tcgtgaaaag gtactttacc tagcgatcgc atgcttcttt 18360
ggtatctaca tcagtttcca cgacgcatgc attctggtac ctgctaaagt aggtactaac 18420
gtcacattga acgcggtaca tgtgcatgac ggtgactatg tgtactggtc ttttggtgga 18480
ggtggagcta atagattaat gtgtcgctat acaccaaggc tagacgaaat tcacaaaaac 18540
accaatcgaa gtttttcatg tcttacaaat cacagtctcc ttctcatcaa tgtaacggaa 18600
gaatatactg attactatcg caccatgacc acattcgtac atcagtccca taattggcac 18660
aaccacggca acaaatggac tttagacaca tgttattatg tatacgttac ccaaaacgga 18720
acacttccca ctaccaccac caaaaaaccc actacgacca cgagaacgac aactaccacc 18780
acaacaaaga aaacaaccac cacgagcacg acaacgacca ccactaccac caagaagacg 18840
acgacaagca ctacccatca tcgacactcc aatcccaaag aatccaccac ccctaaaacc 18900
cacgtagaac ttcacgtcgg tttaggagcc acagcagcgg aaacaccgtt acaaccaagc 18960
ccacagtacc aacacgtggc tacacacgcc ctctgggttt tagcggtcgt aatcgttatt 19020
atcatcatta tcattttcta ctttcgaata ccgcaaaagc tgtggctgct ctggcagcat 19080
gacaagcacg gcatcgtgct catccctcaa accgatctgt gagcaagtcg cgtaggaaat 19140
gattgcatga aatcactgtg aaacgccaac tccgtgccag ctggcgcggc ggacaggcct 19200
ttgacgtatt tgaagccagg cgcgctctcg ataccgaaag gatccgaggg ggctttccaa 19260
agccgacgtc cctgattccc ttcataaagc tgttgaccgg ccctagaaag accaagagca 19320
tgctgtgggc ccactgcggt cgcttcttgc gttatcatct gctcccgctg ctgctgtgta 19380
gactgccatt cttactcctt ttccagcggc cgcagtgggc ccacggcttg gacattgtcg 19440
aggaggacga gtggctacgg gagatacaag gagcgacgta ccagctgtcc atagtgcgcc 19500
aagccatgca gcacgccgga ttccaagtca gagcagcgtc ggtcatgacg cggcgaaacg 19560
ccgttgacct ggaccgaccg ccgctttggt cgggatcgct cccgcatttg cccgtctacg 19620
atgtgcgttc cccgcggccg ttgagaccgc cgtcatcaca gcatcacgcc gtatcacccg 19680
aactgccgtc gcgagacggg atacgttggc agtaccaaga gctgcagtat ctggtggaag 19740
aacaacggcg gcgaaatcag tcgcgcaatg cgattccgag accctcgttc ccccctccgg 19800
atccaccatc gcagccggca gaggatgcac gagacgcgga cgcagaacgt accgaatcac 19860
cacatagtgc agaaagcacc gtcaggcacg acgcgagtga gaacgcagtg cggcgacggc 19920
acgaaagacg gcgctataac gctctgacgg tccgcagccg ggactcgctg ctcctgacgc 19980
gaatacgctt ctccaaccaa cggtgtttcg gacgcgggcg tctgagacat cccgcgggaa 20040
gcggtcccaa caccggcgga ccgcgacccg gcggtgcggg actccgtcaa ctacgccaac 20100
aactgacggt ccgctggcag ctgttccgcc tacggtgcca cggttggaca cagcaggtct 20160
ctagccagat cagaacccgc tgggaggaaa gcaacgtcgt gagccagacg gccacgcgag 20220
tacgtacgtg gttcgtggaa agaaccacgt tttggcgtcg cacgtgggtt ccgagacaga 20280
acccggcggc cgaagcgcaa gaactggccg tcataccgcc ggcacccacg gtgctccggc 20340
agaacgagga accacgtcaa cagcttacgg gagaggagac aagaaattca acgcacactc 20400
aacgtgaaga agtggaggac gtttcgagag agggcgcgag agaagggaat gatgggagcc 20460
gagcaagtgg aaacgacgag agaaggaata atgcgggaag atatgatgat gatcatgagg 20520
ttcaagagcc gcaggtcact tatccagcgg gacaaggaga actgaatagg aggtcacagg 20580
aggagaacga ggaaggtgga ccgtgtgaat cgccgccaat gacgacaaat acgctgaccg 20640
tggcctgtcc gccccgagaa cccccgcatc gtgccctgtt tcgtctatgc ttaggactgt 20700
gggtctcgag ctacctggtt cgacggccca tgacgattta gaatacaccg agccattcct 20760
ttatttcccc ccatccccgg tcgcttatgc gtgttaaaca ctaccaataa agataatctg 20820
ccaatcgcac cttatatata atatgtggtc gcgtgtggtc tttttaagga gctctgaaac 20880
acagacaggt atgggcggtg gtcggctgcc gccgctgtgg ctgccgctac tgatcgcctg 20940
gagcgagtgg ggcaactgct gcctcgatgc gcctccggtg gtgcgttcgc cctgtctgca 21000
gccggtgcgc gaccgcaacc gcgagcggaa cccgggctca ccgcagttgc tgccttacgg 21060
cgaccgtctg gaggtggcct gcatcttccc cgcgcacgac tggccagagg tctctatccg 21120
agtccacctc tgctactggc ccgagatcgt gcgttcgctg gtggtggacg cacgcagcgg 21180
tcaggtgtta cacaacgacg ccagctgtta catcgccggc gggcgctggc gcttcgagga 21240
cggcggcgcg gcgcagcggc tgagcctctc gtttcggctc atcaccgaga ccgcgggcac 21300
ctacacctgc gtgctgggca acgagaccca cagcctggcg accgagacca cggcgctggt 21360
ggccgacgtg cacgacctgc gccactcgga ccgctcctgc gacctggctt tcggatcgcg 21420
ctcacagacg cggtacctgt ggacgcccga tccctccagg ttgcgcagta taaactgcgg 21480
ttgggagggt gaacggcacc gcgtagtcca ctacatcccc ggcacctcgg gtttgctgcc 21540
ctcgtgcgag gaggacgagc gcgaactgtg cgtgcccttc atcagccaga gcattgcgga 21600
caacaactgc agccgccggc atcgagttga cggcgctagg cggcgctatc atctacggag 21660
ggattactgg ctgacggatc cgaagatcgg gttgctggcc gcgggatcgg tggccctgac 21720
ctccctctgc cacctgctgt gctactggtg ttccgaatcg taccggcgtc tgaacaccga 21780
ggaggaaagc gaggcggcgg aggaaactgc cgcgggagaa gcctctgcgg tagcggcggc 21840
ggccgtctct gaggaagagc agcggcggga gtaaacgagg agagccatga agcggatgat 21900
tcgcagtcac ggcaggaaaa cggaatgtca gatgacgagc gccggcgagc gacgcggctc 21960
cgccgtcggt gcgcccatct gcggcagcgg tacccgacgc ggcagcggcg ccaacgaacg 22020
ccgcgactcc gacgtcggtc ccatcgccca cagtagcggt accagacgcg gttcggcgaa 22080
tgaaacgtcc gcctgtacgc ggaccgatca ccagaaggcg gacattgggc tgtggttcat 22140
gtttctggtt tttggactgt gttcgtggtt ggcgatgcgg tatcgcgcac aataaatttt 22200
gaatcgatgt caaggaacgc gtgttttgta ttttattggg aatattggcg gggataaacc 22260
tgtttcggat gtttaccctt aatcttaccg gggacctcgt tgtcctctcc tccttcttcc 22320
tcggacaccg ggctccatgc tgacgtaggt accgactggg gtcaaaagcc tgggtactta 22380
tgaggagcgc gcacaaagga ccgttaggcg ccggcatgga gcgtcgccga ggtacggtac 22440
cgctgggatg ggtgtttttt gttctttgct tatctgcctc ttcctcgtgt gctgttgacc 22500
tgggtagcaa gtcctccaac tcgacctgcc gcttgaatgt gacggagttg gcctcgatcc 22560
atcctgggga aacgtggacg ttacacggga tgtgtatttc tatctgctac tacgagaatg 22620
tgaccgagga cgagatcatc ggcgtggctt ttacttggca gcataacgag tctgtggttg 22680
acctgtggtt gtaccagaac gacacggtga tccgcaattt cagcgacatc accactaaca 22740
tcttgcaaga cggactgaaa atgcgaaccg tccctgtgac taaactgtac accagccgca 22800
tggtcactaa tcttaccgtg ggccgctatg actgtttacg ctgcgagaac ggtacgacga 22860
aaataatcga gcgcctctac gtccgattgg gctcgctata tccgagaccg cccggatccg 22920
ggctcgccaa acacccctcc gtaagcgccg acgaggaact gtccgcgacc ttggcgagag 22980
acatcgtgtt ggtctcagcc atcactctgt tcttcttctt gttggcccta cggatccccc 23040
agcgactgtg tcagcggctg cgcattcgcc tgccgcatcg ataccagcgg ttacgcaccg 23100
aggactgaac ggataaccgc aaaggccacg tgcaacgttc acgctgctat aagaaggcca 23160
tgtcccccgt ggacgggtct ctttgacacg agcgcggcac gccgttgcca cgagcatgga 23220
tcacgcgctc ttcacacact tcgtcggccg accccgtcac tgtcggttgg aaatgttgat 23280
tctggacgaa caggtgtcta agagatcctg ggacaccacg gtttaccaca ggcgccgcaa 23340
acatctacct cgacgtcgcg ctccgtgcgg cccccagagg cccgccgaga ttcccaaaag 23400
aagaaaaaag gcggccgtcc ttctattttg gcacgatttg tgctggctgt ttcgacgact 23460
tttctttcct cgggaggact cagagccact gatgtcggat ccggcacggt ctcccgaaga 23520
ggaggagtaa acaacacacg gctaagagga tacatcatca aagaagatag gaggggtcaa 23580
aacgcggact gaaagtatat aacgccgatc atgtccgagg aactgttaat aaaacgccat 23640
gatgacaatg tggtgtctga cgttgtttgt gctgtggatg ttgagagtgg tgggaatgca 23700
cgtgttgcgt tacgggtaca cggggatttt cgatgataca tcgcatatga cgttgaccgt 23760
tgtggggatt tttgacgggc aacacttttt tacctatcac gttaattcca gcgataaagc 23820
gtcaagtcgg gccaacggta ccatttcttg gatggctaac gtctcggcgg cctaccccac 23880
ctacctggac ggggaaagag ccaaaggtga ccttattttt aaccaaaccg agcaaaacct 23940
gttagagctg gaaattgcgt tgggttaccg gtcacagagc gtgctgacgt ggacgcacga 24000
gtgtaatacc acggaaaacg gtagttttgt agccggttac gagggatttg ggtgggacgg 24060
ggaaacttta atggagctca aggataacct gacactatgg acgggcccca attacgaaat 24120
tagttggttg aagcaaaaca aaacgtacat cgacggtaaa attaaaaaca tcagcgaggg 24180
ggatactaca atacaaagga actatctcaa gggtaattgc actcaatggt ccgtcattta 24240
tagcgggttt caaccccccg tcacccaccc agtggtaaag ggcggtgtcc gaaaccagaa 24300
tgacaacaga gctgaagcat tctgtacatc ttacgggttc tttccagggg aaattaatat 24360
tacttttatt cattacggtg ataaggtgcc cgaggatagc gagcctcaat gcaatccgct 24420
acttcccacc ttggatggga ctttccatca gggatgttac gtagccatct tttgcaatca 24480
aaactacacc tgccgcgtta cacacggtaa ttggacggtg gaaatcccca tcagcgttac 24540
ctcacctgac gacagttcct cgggggaggt ccctgatcac ccgacagcta acaaacgcta 24600
taacaccatg accatcagca gtgtcctcct agccctgctt ttatgcgctt tgctattcgc 24660
gttcctgcac tactttacca ccttgaaaca atacctacgt aacctggcct ttgcgtggcg 24720
ctatcgcaag gtccggtcgt catgaccagc aacgccctgt atgagctgtt tcgacgtagg 24780
ttaccgcgtg cccccgtcaa cacggtcatg tttctcacgc gacgcactcg tgatgggttc 24840
tgcggtcggt tgacgtccat cgccacgaat tcccactaca ctatgttcgt gttagatcac 24900
gggtccgtgc gcatcgagcg accgagtcag tcagaagtgg attgcgccag tttaatggaa 24960
acgctgaagc ggattcggtt acgaaattcg tgggtagcgt cagaagacga gctagatgtg 25020
agtcgcgggg acgcgtgaca caaaacgcgt tcaggattaa cgtaggtttt cgaaataacc 25080
tacgtccgtg agtgacgcgg tttcgtgttg aaacccgcgc cggttctcac ggtggtttat 25140
gatgaaaccg gcgttgggga tctacgcggg ttcctcattc aacctgcgaa aagaggaagt 25200
tgcggtaaaa ccacgtcaat aaagacgtca atgacacctc aatgttgcgt tggaacggtc 25260
tttatatata caaacgccgt tatgttcagt gtccggcaag atgctcggga tacgggctat 25320
gctggtgatg ctggattact actggataca gttgataaca aacaatgaca ctcgaagcaa 25380
caataccgat accatctttg tatctctcct taccggggcc aacggagtta ctcgcacagc 25440
catcgggggt ctgcattcaa actacaccaa cttaaccgag gcattcagat tcactccagc 25500
aaacacaaca actaactctt ccacggaggg taattggagc gtgactaacc taacggagag 25560
ttgcatcaac cgcggtgagt cctatctaac taccatctgg cttctgaact gcgctgacaa 25620
caatacttat tggtactctg gaaatgccta taaccataca attgacactt gtaaaaatac 25680
agtttcggga tatctcttct tcggcatgtg ccagctatgg aaagattggg ttactaatgc 25740
ttctcacgac actgtcagaa ttcagtcgtt gggaaatgaa atacgctgca tgctgctccc 25800
tagacagtat accctcaacg ccacggtgga atggtacaac aaatctgaag gtgacgtacc 25860
agaagaattt atggactatg ttatcctgac ccccttggca gtgcttacat gcggactgca 25920
ggaagcttat atactcgaca agggtcgtag atacatgtat ttgttttccg tgtcctgcgc 25980
gggaatcaca ggtaccgtat ctattatact cgtctcccta tcgctgctca tcctcatctg 26040
ttactatcgc tgtggccggc ttctgatatg cccacgcggc tttgaactct tgccagaatt 26100
cactgaggaa gaggaggaaa aagaaaaatt gttaacgtac aaggacattg aagtccaggt 26160
gcctatccgc acgcggcggc tgctcgtccc ttggatccgg gagagcaaaa tgtgggtact 26220
accacccccg ctgcctccac gacctcccca cttaatagaa ttcccgccgt ctcctccgcc 26280
gtcgcctggg cccatgcaca tggtggtctg catgccagca tgacggactt tgaactttga 26340
gccccaagcg gtacggacta catattttcc ataaatctac actgaacttg agcacaaaaa 26400
tactgacaat ggactgaata tacagacttt tatatgatcc ttgtacagat gtaaataaaa 26460
tgtttttatt taaaactggt cccaatgttc ttcgggaatc atggggtggg gacgggggac 26520
gcggtaagga gcaaaaccgg gtacatgggg gggaacatcg tccagcagta gcaccagcgg 26580
attgggtagg ggttgctgcg gaggtcggtc gatgacgatg tcgatctcca tcggcagatc 26640
cggcaacatc tcttcgtctc cctcaccgac cagcactcgg cgctgttctg gatgtatatg 26700
attttggaaa agcctccgac gagctcgcgg cgcgtagaaa gccaagcggc gcaagggccg 26760
gcgagcccga aagtccatgc gcacagatgg catgagtcct tgagtgacgg tggtgagctg 26820
gggaacaggg ctacctccca tcgcgacggt gacagtggat ccatgagaga ggcgccgcac 26880
gctgcatggc taaataccgt gaatcccctg acgtcgtctt tcgtcccgaa cgcgtcatgt 26940
tgggggcgag gcgtaaaccg tcgaggttga aaaaccgcgt atctgcgacc cgtccggact 27000
acgttgtttt tcagaagcgg ccacatgacc tcgagatgtc gtcacccaag gtatttaacg 27060
gcacacagcc agacgcgttc gtcagcagcg acgccgacaa gacctcagca tggctcggag 27120
gctatggatc ttgagcttac tagccgtgac cttgacggtg gctttggcgg caccttctca 27180
gaaatcgaag cgcaggtaaa cggaatctgg ggaattcaac acaggtaaga aatacaaaaa 27240
ataacgtgat tgtgaacgcg gttatcgtgt ttttgcagcg tgacggtgga acaacccagt 27300
accagcgctg atggtagtaa taccaccccc agcaagaacg taactctcag tcaggggggg 27360
tccaccaccg acggagacga agattactcc ggggagtatg acgttttgat tacagacgga 27420
gatggcagcg aacatcagca accacaaaag actgatgaac acaaagaaaa tcaagccaaa 27480
gaaaatgaaa agaagattca gtaacagcag accccaaggg ttaacgatta tgttgactac 27540
cttgtttttt attaaaaagc tgtaaggttt tgctctaaaa acaccccgcc tccggtcttt 27600
tttcttttgt attcggcacg cgaaacacgg tttcttccca tagcctgtct aactagcctt 27660
cccgtgagag tttatgaaca tgtatctcac cagaatgcta gtttgtagag gctatgcggg 27720
atgctgcggc ggcgcgacct tccctctcca cccagccccg tcaaaacaca cgcgactcga 27780
gcggttcgta tgaaaaataa aaaacagctt tttatttaca ggaacgggga aaaaaaaggc 27840
acacggtccg tgggagacgc gggttcacgc gtcgtcaaaa agttggtggt ccactccgta 27900
aggacaggta ggcttattta gcttccgcat gctcctggtt ccgtaataaa tgccgttttc 27960
gtggcagcgt gtcatgccgc gagtcacaaa ctccatcaaa ctgtcggcca cgatgcaaac 28020
gtgctgattg ttggcagcaa agacgcgcat acagtcgtcc acgaagaggt tgatcacgtc 28080
gtaggggctc accaaccagc ctaaaggttc cacgtggtta ctgccgacca tgaccctcca 28140
gtcgttaatc tcgctccagt cgtacagccg aatcgtggag acgcgaatga cgctgtaatc 28200
acccatgacc atgagtcggc cgcgatacgt agcacgccac tgcgcgaacg cgtggatgtg 28260
catgcagccg gccagcgctc taagcgaggc ggtgtgcggc agctcctctg ggacggtgat 28320
gaagttgcag cgtcgcaaac cgatgttgag aaattcagtg atgctctcgg ccacaaaggt 28380
caacgagtca gagtagatgt ggtcggtcca caggtacatg gcgcccgagg cgcccaggta 28440
cagttcagac ggcacgttgt gatcgccctt gtgtttaaga aagttgtagg tgcagatgct 28500
gccgacgaaa cgcagcggct cggggcagca gaggtagctg gccagacgct gtgcatcccg 28560
tccttcgtcg cgcaccaagc gccagcgacg ccggataacg aggcagcggt ctttgggcca 28620
gaccagggcc acgcgttgcc cgggtttcca cggtcgcgac gtcttaggag gcctccagcg 28680
gtcgagcaga ttgagaaaac agtccttgat taccgacatc gcggtcgcgc gtcggtggac 28740
aaaaagaaat cgggccgatc cggaaaaaaa aaacgacggc aaaacaccgc cgtgctcgag 28800
cgaagggtgg cggagggcca gaagaggcgg ccttgacggc gttggcagcg aaaaaattgg 28860
cacgcgagtc aaacgggaag tagcgtcggt gttttatgcc ccaagcagcg tcgtcgtcac 28920
tcgtggcgtc acagtcaacg gtgctgacgt cctttggggc agtcgggcac gcgatcgtag 28980
atgccgttgt ggccgctgaa acgtcggttt tcaaacagca ggttaagtcc cagacacatg 29040
aacgtgttga gattatctcc cacccggatg tagcggtcgt cgcgcacgtc gcaggcgtag 29100
acggccccgg tataggcgac gacgatgggg ataaggtcga cgggccagcg caagtgagga 29160
aagggcgcgt tctcgccctt gaggctgacg gttcccaggc cgagaacgcg cattccgaaa 29220
gcggttttga tgttgcgcag caagtgaccg ccttccacgc tgttttcgaa acacctgagg 29280
ttgcatagac gcagttccgt tcccggcggg tacgtcaacg gcatgaactg cccgtggtgg 29340
cggatgatga atcgcgccat ggtatccaaa ccgaggctcc aggcgcgcaa cagcgggcga 29400
aagtagcgct taaccaacga cgaggtcagg tagcgcatgc agtgcagggt ctcgacggcg 29460
cgcagcccga cgcgcgcaaa ctccatgagg ttgcgggcca ggtagtagac ggcggtgtcc 29520
tcgcgtacat agcaaaaaac atagccctcg tccgagatga ggcacacagc ggtcttcttc 29580
tgctgatccg gcgacaacac gccctcgttc acgaagcgac ccacgaaggc caggcgcgtc 29640
tggcaacaca ggtagtgact ccaagccttc acgtcctccg gtttgaagtc ctcgtccgtc 29700
tcgatctcct gcagcactag gttccagccc ggcggccaga ccacgggcaa cacctggcct 29760
gcgttgatgc gcacgtaagc ttccagacag cccaggccga actcggccgt gagcgccagg 29820
ctagccagat cgctcatgtg acgcgccgag tcagtgggcg agcccggggg cccgtcgcac 29880
accacgctcc gtcttcttgt cctcaccgcg gccagcgtgg cgaggacact ttccgcgccc 29940
gaggctgtat cttcggtttg cccgccggag ccggccctca ctatataacg tcccgcccgg 30000
gtctcctcca tgtatgcagg taagcaactg agccgaacgc acctcagcag acgagaggat 30060
gtcgtcgcgg cgtcgcagct cgtcacgtcg ctctggcgaa ccctcgacgg tgatttatat 30120
cccctcgagc aacgaggaca cgccggcgga tgaggaggcg gaggacagcg ttttcacgag 30180
cacgcgggcg cgcagcgcca cggaagatct ggatcgcatg gaggccggtt tgtcgcccta 30240
cagcgtctcc tcggacgctc cgtcgtcctt cgagctcgtg cgcgagaccg gcggcaccgg 30300
cgccgccaag aaaccgagcg aaaagaaacg atcgtcgtcg cgtcggcaac cgcagatcgc 30360
agcgggcgcg cctcggggct cgccggcgac acccaaggcc ggcaagtcgc ctaaagtctc 30420
gcgaccgcct agtgtgccct cgctgcccga gaacggcgcc ggcggcggtg gcgacgataa 30480
cagcagcagc ggcggtagca gcagtcgcac caccagtaac agtagcagaa gtaccagtcc 30540
cgtggcgcca ggtgagccgt ccgctgccga gggcgatgag ttttccttct gcgacagcga 30600
catcgaagac tttgagcgcg aatgttaccg ggtcagcgtg gccgacaatc tgggcttcga 30660
gcccagcgtg gtcgcgccgc agcacgtcga gtatctcaaa ttcgtgctgc aagactttga 30720
cgtgcagcac ctccgccgcc tcaacgaatg catacccatg ccggccttcg cgctcaccag 30780
cctcgtcgac cccgtcttaa acaacgtagc gcctggcgag cgcgatctca cgcgtcggat 30840
aatcacgcac gcggtgatca tcaactatta ctacgtggcg caaaagaaag cgcgccacat 30900
ggtggaggcc atacggacca ccgtgcgggg cgacacggta cgccgggtag ccgcgcaggt 30960
caacaaccag agccgttcgg ggcgtgcggc cgcgctagcg cttcattttc tcacgtcacg 31020
aaaaggagtg acggacggcc agtacgccac gtctctgcgg cggctggacg aagagctgcg 31080
gcatcgcggc acgcccgaat cgccgcggct caccgaggtt taccagacgc tacgcgatta 31140
caacgtgctc ttctataccg cccactacac ctcgcgcggc gcgctctacc tctatcggca 31200
aaacctgcag cggctcaacg agaaccaccg gggcatgctc cggctgcttt cggtcgaaga 31260
gatatgcgaa gagcacacgc tcaacgatct ggcgttccta gtaggcgtcg agcttatgat 31320
cacgcacttt caacgcacca ttcgcgtgct gcgctgctat ctccagcacc agctgcagag 31380
catctcggag ctgtgttacc tcatctatgt acaactgccg tcgttgcgcg aagactacgc 31440
gcagcttagt gacgtgatct actgggccgt cagtcaaaac tacgactacg cgctctacgc 31500
gagcacgccg gcgttgtttg actttttacg cgtcgtgcgt cagcaggacg ccttcatttg 31560
caccgactac gtgtactgcg ccctgcgtct gctggcctgt cccgacagac ctattatcgg 31620
tgacaccggc ggcagcagta gctcccaacg cctcgtaggc gagtttatgg tgcgcgatcc 31680
gctgttgcgc gacccgcgcg ccacccacct gcgccagaaa ctcatcaccc gcgacatatg 31740
cgtggcgcgg ttgcaagcgc agccctcgag tcgacacatt ccggtcgaac acacgggtgt 31800
ctcctccgtc accctgctca aaatctttag ccaagtcccc cccgacgaac gcgaagaaga 31860
cacgttacgc gagatggctc ttaaagcgtt tatggaagcg aacggtaatc accccgaaca 31920
aatctgccga tccccaccac ccccgctgcc accgcgcgac tatcctcaac gcgacgagcg 31980
ggaccgtcac cgtcgcgacc gccgcgacag cggggaatac tgttgctgat ggtgggacga 32040
aacagcaggg cggaacagtt tatgatagaa agtcacagga aagtatgtgt tgtttttttt 32100
ttaatgtacc aagaataaaa agtgcgtcta cgaccaaagc ggtgtgtgga cgctcgtcct 32160
ctctgtcttc tccgggtttt tttttcacgt gttttttcct tcctattttg ttacggcaac 32220
agcgctgatg gcacgttgcc ggcttcgaac atcgcgtcgg tgatttcttg cttgcccggc 32280
gtcacacggt gacgtagcag cacgcggctc acgtagcagg ccgactcgcg gatgacctgg 32340
ccgtcggcgt cgcgtcgcag gcccgagcgg ttgccgtgac gcagtctgcc ctgcgcagcg 32400
cgctccacgt cttcaaagta gctgtgtagc aggccgcgct ccagcagctg cggcagcgag 32460
tcggcggcgc gcactacaaa gttctcacgg ctgatctcgt agcacagcac gctgccgtcg 32520
gccgccacgc cggccacgct gcggtcccaa ctgaaaaggt tggcgagtcc gatggtgccg 32580
atgacgcgca actgaccctg ggtcaccacc agcagcttcc agtattctac gtcgcgcggg 32640
gtgaggatgg tctcctccac gtcgcagaca aacaacgtgt agccgcgcgg atagggcaga 32700
tccaggtggc gaccgcgctg gcggcgcata aaatcgtcta aattcaaacc gccgtcgggt 32760
gcgcgcctac tcgtcatcgc cgcgccttgt cggtcgatga ccccacggtg cttataacgc 32820
gccgccgcgg cttcatgtgg cgtgacctcc gacctcgtga ggccgaaaac ggcgtacatg 32880
aagacgctca aacttttgaa tgtgggcccg gtagcgcacc gagggccccg gggcggcgac 32940
gacggcgggc ccgagttcca gcggggcctt gcggcggcag cggttggcgt ggttgctcag 33000
ctcggcgtcc gagagcgccg agctgaactg cggcagccgc gtgcgatcct gcggcgcgtc 33060
cccgtgtcgc agcgagtgcc agagcaggcg ctggacgcgc gccgtctcgg gcgtcggcgg 33120
cgcgcgacag ccccggcgca gcttgaaaac gtgcaggcac agcagctcgc gcttgatgcg 33180
cagcgacacg ctgcggtagt cgggaatccg ctgcaccagc tcgagaaagt cgcagaaggt 33240
ctccacgaac gtgtcctcgg tgaagcgaat gcgcttcaga tcgtggacgt gtttgcgaaa 33300
ccgcgacagt tctcgacgtt gcacggggtt ctgagcgagt cccttgcgca gcagcgcagc 33360
ctcgccttta aacagcctga tgagccgctg cacgtccccg ctcaacatac gtatacacgc 33420
cgtgtactcg tgacgtatac tggcgcgcag cagccgaatg atacgcaggg ccagcacggc 33480
gttagaggcc aggtacatgg cgtagccgcg acgcgggttg gcacaggccc agcccgcggg 33540
gagcagaaag tagtcgtcga tcagcgtctg cgaccagtcg gcgaagccca ggtcacgtga 33600
tacgctgtcc tggacgcggg ccacgtcgcc ggccgtgagg tggcggatcg ccggcaggtg 33660
aaacgcgccc aggtgtcggt tgcgctccag cctcagctcg gcgtgctcca aacgggaatg 33720
gtgggacgcc accgcggagg gcgacaaaga ggagtggtca ttgccgtcgt ggttaccgtc 33780
gtggttaccg ccgttgtcgc gcccgtcgcc gcactcgcaa aaggccgcgt agaggtcctt 33840
caatgccgct tcggctcgcg ccataaacgt ggcgtggaaa aaaacggcgg cgcggtgcgt 33900
ccggtacttg acgggcaacc cgcggcacag ggccgccggc aggcagcggc cgatgagttc 33960
gcgctcctcg ggctccagaa acaggcacag ggtgccgtcc aggcgcaggt acagctcctc 34020
ggtcatcgag catagctgcc gcaagtaatg ggtgcgcgtc ccaaaggtct tgtaatcgag 34080
caacgtgcac accacgtatt gccccgtggc cacggccaga gcgatgcgtt tggcggcacg 34140
actgatctct ggcaagtact gcgcctcgtg caccagacgg cggaaagcgc cggcgttgag 34200
ccagcgaaaa tgctgcggat cgggcggcaa gggcacgcct cgaagcgcgg cccagacagc 34260
gaggtccgac tcgagcgtca gaccgcggat gtcgtacttg ccgtgcgccg tagcgcaggc 34320
tgaatggacc agacagctgc ggcgaatgta caccatggcg tgcttgggat gtttgggcgc 34380
cggcgttttc tttttctgac cgccggcggc cgccagatcc tcgggcgtgc gacacaacag 34440
gccggcgcgc acagcctcct gtcgattacg aatcggcgtc aggtaggcgc gcaggaactg 34500
gtgacaaaac tcctcatcat cacgacagtc gtcgagatac tcgtacgtgg tgagcggatc 34560
gcgaaatagg cgctcgtcac cgtcgtcatg gtcttcttta gcctgctcct ccggctgctg 34620
ggttggcagt ggaggcggcg gctgatccac ggggttcatg actgagagga agaagaaggt 34680
ggcggcgaag cgacgcggag cgacggcggt aaagccagac accggctata tagctagtca 34740
tcacagtctc ctccttcacg acgcccccgt gccgctcacg ctatccagca cgctacggcc 34800
cgaaaacacg tactcgctga cgtcgtacgc gggcgatgta tggctgctca ccggtttcgc 34860
ggcgacggtt gcgctcgagt ccaacggcga gaagcaaaaa cgccgtgggc aacgaaacca 34920
gaaggagccc tgacggataa aaccgcgcag cgtctcggcc aacttaacca gcatcgtacc 34980
gtacagcagt acgtgaatgc cgccatgcgc gtccataaat acggctttgt tcacgggttc 35040
catccatccg atgactacaa aatgggcctg ttctagcacg ccgatcacga aattgttggc 35100
ctcgtcggcc tcggccacgt tccacgagcc gaaagtgaaa gtacaagcgg gcgagccgcc 35160
caggcggatc ttgctaccgg cgtggagctg acatacgcgc agcagattgg cgcggtcgtg 35220
cagtatctgg gagagttcgt acatgcccgc aaaggtgtgc ttaaaccacg cgccctctac 35280
gatctcatcc acgtagtcgc gctcaaagaa gctgtacacg gcaaagaggc cgttctcaaa 35340
aaactcgccg aacgagagcc ccagcacgta caccttgtcc tcgccgggca ggtacgcaaa 35400
ggcgtgcccg tgcccggaga cccagatctc gggcgccgtg tttgcgtccg gcacgcattc 35460
gtacacactg acgaggccga taaagtacaa gcggccagcc tggcgcaggc acgagaagcg 35520
ccggtaggtc ttgtgatcgc gcaccacccc aaagtactga gtgtcgccca gcatgatgcc 35580
gtgcagcggc ggccagcaca gcgggagcca acgacccgcc gtggcgcgca cgtagcgctg 35640
caggtgaacc ccgctcgcac gctcgcgcgg cttcgggcgc ttgtgggtcc aggcatcacg 35700
cagaccgcgc cagatgctgc tgaacttggg ctgcccgcgc agatagagcg acgagagcga 35760
gtcaaagtag cccacgacga gcctgtcggg agacacaaga gcgcgaaaat caaacctaga 35820
gcgacgacgg tgaaaaaacc gaccagaagc gcgtgtctca aacacgctac tttcggttat 35880
aaaaacaccg tcgccctatt tctgggcgcg tgtacactga tgactcacct acgctttttg 35940
aacggcagtc tcagctcggg attggcctcg tacagcgagc tgcggtccac ggggccgatg 36000
ctctcgtagc gaaagtcgtc gatgagcagc gccagcccca cgcgcacgaa gcccctgagg 36060
tcgcgcgcca gccgcaccaa cttatcctgc cccaccagcg ccgcgtacac ggtgcccgtg 36120
tcgccgcaga gaatccgcac gcggtgaaag aaggtcttgt cctcggcgcc ctcaatttcg 36180
cccagcggca tgacgggctc gcgcgtgtac aacgaacgtt gaaagcggcg cagcatcgag 36240
gccgagagcc ccagatcgcg cgccgtgcgc agcactaggg aatgcttctc gggccagatg 36300
agggtcagtt gcgcctcgcg gtgcgcctct acgtaggcgc aacgagcggc ggtgtcctcg 36360
caggccagca actcgcggaa agccagcagc gaacgtaggt agcggccgcg agcggaggcg 36420
cgcgagcggc ggcacagctc ggcccgatgg tcgggatgca ccaagggcac gttaggttgc 36480
agacgcgcgc agatggattc gtgcaccggg tcgcagcgga tcatgccctt ggcaaaaaat 36540
ccggccagat ccgaggccaa ctcgtacagg cagtcctctt gcgcgtcgta ggcgaacacg 36600
gcgccgtacg cgtccacgaa cacctggtac cggcaggtgg cgtgcgagac cgtgccaatg 36660
agatgcagag ctcggaattc gccgaaaaag tcgttctggc agtgctccag atcgatctcg 36720
gtcagcgagt gcggcgaatg ctcgcccccg accacgtaga tgcactgcga gggccagccc 36780
agcgacacgc acgagccctc gaagcgccgc aagtaacgcc gcaggccctc atagtcgcgt 36840
cgcacgcaca ggtcggccaa gtcgcgcgtg caaaagacct cgggtaccaa gcagcgtttg 36900
cgacgcggcc gacgcgcgtg cccaggcaga ggaggaaggc gcgacggcgg cgacgacgag 36960
gaggaagacg ccgtggccgc cgagcagccc ttgcgacggc cggacatgcc ggcagtccgc 37020
gacgatccac aggagacaaa aaagcagaag cagcagtagc ctcggcgacc cgctccaccc 37080
cgtcctccac acgctcagcc gcgactgaac gccggggcgc gccgctactt gggtttttat 37140
agccatctgc cccccgtctc gggcacccgg gagcgatcta cggagacctg acagcagttg 37200
ggcaacacaa gatagggaaa tacaaagaca cttttaataa aaaacgagac tactttgtgt 37260
gtgtgctccg taaactgttt attctccccc tccgcttcgc tctggatggg ctccgggtcc 37320
gtcaacacgc gactcgcgcg gcaaaaggca cgctgttgac ggcgcgagag cccgtcgtga 37380
tagtccatca tgccccggag atcgtgcaca aagcagctgt cgccgcgcag aaaccgacgc 37440
agcgtctcca cgtgctgcag ctgccggcgc gtatcaggag ccgtcatcgc tgatgtcgtc 37500
atcgccctga caggcgcgta gatggcttcg cgagatcatg cgcgttttca accgccgtga 37560
cacatcaggt ccatcttgag ctggcgccgg gcctcgcgca ggtgttgcac gcgttgtgag 37620
cgggaggcga gttcggcttc ttgctcgaac tcctgctgct cactgtccga gagggtgcga 37680
taaaaggcgg caaagtcctc caagtcggct acatgcgccc tgggtctgac gctccaaagc 37740
gtacgcagtc tgatgaagcg gacccatcga gcgtcacggc acgccgtctt gaacgcgggg 37800
cccgggaaga ggttcttctc cccggcgcgc tcgggccggc gaggccgacg cggtttatat 37860
acaccgtctc ggacggcggg acgccgagcc cgcgccgcgg ccgctcatcc ggagacggcg 37920
gaaaccgcga cgccggagga aacggggacc ggcaacgacg gcggtggcgg cgaccagatt 37980
atgggggaca aacccacgct tgtgaccctg ttgaccgtcg ccgtgtcgtc gccgccaccg 38040
tcgtcgccgc tgccgctcgt cagcttcacg gagctgttgt taccgccgcc gtccgtcgcc 38100
gccgctgcgg tggcggcgac agcgacgagc gaggtgggcg agaaaaccgc ggagcaagag 38160
gtagcggctg cggatccgga gaccgggaat gagagaagag aaaacaggga gaacgaagga 38220
ggggagacga ggacgacagg caccaccgcg gtcaaaaggt cgcacgacgg tatccctcgc 38280
caactggcag agcgcctgcg gctgtgccgc cacatggacc ccgagcagga ctatcgtctg 38340
ccggcgcagg acgtggtgac ctcgtggatc gaagcgctac gcgacgcgga ccgcgacaac 38400
tacggtcgct gcgtgcgcca cgccaagatt caccgttcgg cctcgcacct gacggcctac 38460
gagtcgtact tggtgtccat caccgagcag tacaacacgg cctcgaacgt gacggagaaa 38520
gcttcgtacg tgcagggctg catctttctc tcgtttcccg tcatttacaa caacacgcag 38580
ggctgcggct acaagtacga ctggtccaac gtggtgacgc ccaaggcggc gtacgccgag 38640
ctcttctttc tgctctgctc caccagcgag agctccgtgg tgctgcaacc gctcatcacc 38700
aagggcgggc tctgctcgtc catggcggtt tacgacgagg aaaccatgcg gcagtcgcag 38760
gcggtgcaga tcggttttct gcacacacaa ctggtcatgg tgcccttcgt gccgcacgcc 38820
tgcccgcatt acgccgtgcc tttcacgacg ccgggaaagc cgggctgcgg cggtgctccg 38880
agcggcgttg cggggttgga ggaggcggcg ccctttggac gggtcagcgt cacgcggcat 38940
ggcgcgacgc tgctatgtcg cgtggaccat ctgacctgga tcagtaagcg cgtaaccacg 39000
tacggacaca aaaaaattac gcgctacctc gcgcagttcc gcggcacgat ggacgacgac 39060
gaggcagcgc tacccggcga ggacgaagcg tggatcgcgt ccaaaaacgt gcagtacgaa 39120
ttcatgggtc tcattttcac cgtcaacgtg gattcactat gcgtggacgc ggaacagcgc 39180
caactgctgg gcaccgtggc cacctccttc tgtcaccgcg tctcggacaa gatcacggcg 39240
cgcaacatgc cgcgcgcttt ttccttctac ctgctgacga gcgcgcagcg cgggtacgac 39300
ctgcgattca gccgcaaccc gtcactcttt tttagcggcg acgcgctcaa ctgtccgctt 39360
ctcaatgagc ccaacgtgtt ttcgctcacg gtgcacgcgc cttacgatat ccacttcggg 39420
gtgcaaccgc ggcagacggt ggagttggac ttgcgctacg tgcagatcac agaccggtgt 39480
ttcttggtgg ccaacttgcc acacgaggac gccttttaca cggggctcag cgtgtggcgc 39540
ggcggcgagc cgctcaaagt cacgctgtgg acgcgcacgc gttccatcgt gatcccgcag 39600
ggcaccccca tcgccacgtt gtatcaaatt accgagggcg acggtaacgt gtactcgtac 39660
aaccaccaca cggtgtttcg gcagatgcac gccgccggaa caaccacgtt ctttctgggc 39720
gacatgcaat tgcccgcgga caactttctc acgtctcccc atccctgacc ctccgtccgt 39780
cctcctttcc cgacacgtca ctatccgatg gtttcattaa aaagtacgtc tgcgtgtgtg 39840
tttcttaact attcctccgt gttcttaatc ttctcgatct tttggaggat gttctgcacg 39900
gcgtccgacg gcgttttggc gccccccatg ccggcagaac ccggttgcgg ccccgtaccg 39960
ctcttctggg gcgacgatag gtcgaaagcc accgttttca tgcccgtcgt gctcttgacg 40020
ggggaaccta cggcggcggt ccccgtcgag cggcgtgatt gcaaagccgc gctcgccccc 40080
ggtttcagga tggaggggga ggccacaggc ggcgcattcg atacgctgct tttggccgta 40140
gacgacggtg ggtaaacggt ggttaccgcg ggatacgtcg gcgtggtcga ggcggcccgg 40200
ctgctgccgg acaggcgacc cggcgcgcta ccgctcacgg ggaccgaggg cggtcgacct 40260
accaccgcct tgccgcccaa agtaggtttc aaggaaggaa caccgacgcg gctgccccgg 40320
cctttcaccg gagacggggg ggcactcttg gccggggacg gagaggctga cgaaagcatg 40380
gacagcggcg atgtggcggg ggacacgaca tcatcctccg tgggcgacaa aacggacgcc 40440
gaggctgacg gctgtcgagc cgaagaagcg gaagaggttc ccgcgccaga agtcacgttc 40500
cttgatgacg tcgttttaga cgaagccggt tgaggttgca acagcgtggc gggtaccgtc 40560
gacggcgtgc ccgacacctg tttctctagc cttccctgaa ccggcgtcga cgtcaccgtc 40620
tgcgctcggg cggacgcgtg cggcgtcgcg actcgcttgc ccagcaccgg tttctggctc 40680
gtggatgtcg tcgtcattgg agacgataac ttagctttac gtattctgga cggcgtcgac 40740
tgctcgggcg tctgactggg aggcgaaatg acgtcgttgt tgtaatcgga cgacggtgtt 40800
gtgtgtccca ggctgacgac ggagccggtg tccgaggagt cgtcgtcttc ctcctcgctg 40860
tcttcgaccg gtgactctgc agtttggtcc cttaaagccc aaacctcatc agcggcgtcc 40920
cgagacgctg tttgtgtcac cgcggcgcgt ggagtcgacg gcctccgagg ggtggtggac 40980
acggtgtttt gagaagccgt ggaagtcgta ggcatcctga agggattgta agccaggtga 41040
ggattcttga gggcccacgc gcgttcgcgc ggccagttgg cggggttcat atccccgggc 41100
aacggcgccg tcggagccca gggcgagtta ccgttgaccg gggtttgggt acccgcgaag 41160
gtaggtgtcg gggccggagc gggggccgtg gaaggattga caggcgtcgg cgtgaggatg 41220
gcagcgccgg cgccagcagg aacgttaact ccggcgccga acgtcaacgt cggttgctcg 41280
aacttgtacg cggtggtgac gggcggtttg gcgctcgtct cggtatccgt gatgtccacc 41340
agcgtgtcgg tgaaacgcgg atcttgacgg ttggggggat agccatccga gctgtcggaa 41400
tcctcgtcgc ccgagaaaag atcccctctg gtctccgtga gcggcctcac gtcccacgcg 41460
ctgtcccgac ggacccttcc cgggctggcc ttggtcacct gcggggagac gagactgaaa 41520
gccgcgtgac gctgttgttg ttgcgggatg ttcaagggac cgctggtcgg tttctgactg 41580
cccgaggata acaggccgct gaaaatgctg gaaacaccgc caccactagc ggcgcccttg 41640
ccgctagttc ccggtttctt gatgggcgta aagatgtttt tctcgtcatc atcatcgtcg 41700
tcgtcctcat cggcactgga gccaaagagc ctccgggagg cgctcggttt acgtgccggg 41760
ggcggtggtt gctgctgacg ttgctgcagg ttctgctgcc tctcctccca agccttcagc 41820
tgctgtttct cacgctgcac cacctcgtcg tccacccgtt tctgccgctc gcgacgcttt 41880
tcctcttcgt cgtaatagcc gacggccgcc gaacgggcag cgtgggcttc ggcggccggt 41940
gccagagaac catgggcctc gaagcggaac ggtttgtgtc ccttccaggg actggcgatc 42000
cagctccagc cgtccagcgg ctgcgtgggg acatgtttct tgggtaccga cgagaaggcc 42060
gaaccgccgc cgagcgagag gagattggcg tcatcgtcaa actccaacga cggcgagcgc 42120
gcgcccaaaa acgtgtgcgc cgactgtggg aagctgtcca cgtagatatc aaagtcctcg 42180
atgagcagct ccaacagcgt gtcggccgag tcgccgtttt ccacggcgtg cttgaggata 42240
ttgcgacagt agttggaatc aaaggaaagg cacatgcgca gctccttgac cagcagcttg 42300
cagcgctcct gaatgcgcgc cagacatttg cgctccagct cctcccaaga cctgcgcacg 42360
ttcatgatga gacggcccgt gtacacgagc ttgttgacgg cgttgaccag cgccgtgttg 42420
gcgtgccggt ccaggttaag gtcgagcggt ttcacgcaga acatgttacg gcgcacaccc 42480
tccaggtttt cttcaatgcg ctgcacctcc gtatccttga ggtgcacaaa ggcgatgggt 42540
tccgtctggc cgatggctgt gaccagcgtc tcgcgcaccg acatcttggc cagaatgacc 42600
gcgcttacga gcgcgcgttc cacgatctcg gcatcgtggc gcacgtccgt atcgaattcg 42660
gtacggtcta gcacagccag gtggtcacgc gccttaccac gatcaccgaa cgggtaagtg 42720
tagccgcgac gcgccacggc cacgcaacgc acctcgaact cctcgagcac tgaggagagg 42780
tcggggttgt gaaaacgcag ctcgcggtag tatcccaacc aaagcatgag ctcgttgaac 42840
agcaccgtac gccggtgcag gcgtttttcg ccacattttt tcaggatctt ggggtgtgcc 42900
tcgagatcca cgtcgggctt ttgcgtgaga tggcgcagaa agttgaccag ggctaccaca 42960
tcgcgccgct gtagaccgat aaactgcaaa ctcatgctgg cttttctcca gaacccggaa 43020
gcgtcgtcgc cccggactgc gcccgcggtc tgctattcgc ccacgatgga caccatcatc 43080
cacaactcgg tgagcgcccc acctagaggg agggggggta gtttaatagc ggaggcggat 43140
acgcggtttt cttttaagcg ccgctgactt gtttcttctg ttttttcgcc ccgtgtgctg 43200
ttccgcccag acccgcaaca acactcctcc gcacatcaat gacacttgca acatgacagg 43260
gccgctattc gccattcgaa ccaccgaagc cgtactcaac acattcatca tcttcgtggg 43320
cggtccactt aacgccatag tgttgatcac gcagctgctc acgaatcgcg tgcttggcta 43380
ttcgacgccc accatttaca tgaccaacct ctactctact aattttctca cgcttactgt 43440
gctacccttt atcgtactca gcaaccagtg gctgttgccg gccggcgtgg cctcgtgtaa 43500
atttctatcg gtgatctact actcaagctg cacagtgggc tttgccaccg tagctctgat 43560
cgccgccgat cgttatcgcg tccttcataa acgaacatac gcacgccaat cataccgttc 43620
aacctatatg attttgctat tgacatggct cgctggacta attttttccg tgcccgcagc 43680
tgtttacacc acggtggtga tgcatcacga tgccaacgat accaataata ctaatgggca 43740
cgccacctgt gtactgtact tcgtagctga agaagtgcac acagtgctgc tttcgtggaa 43800
agtgctgctg acgatggtat ggggtgccgc acccgtgata atgatgacgt ggttctacgc 43860
attcttctac tcaaccgtac agcgcacgtc acagaaacaa aggagtcgta ccttaacctt 43920
tgttagcgtg ctactcatct ccttcgtggc gctacaaact ccctacgtct ctctcatgat 43980
cttcaacagt tatgccacaa ccgcctggcc catgcagtgt gaacacctca cactgcgacg 44040
caccattggc acgctggcgc gtgtggtgcc ccacctacac tgcctcatta atcccatcct 44100
gtacgcgctg ctgggtcatg attttctgca acgcatgcgg cagtgtttcc gcggtcagtt 44160
gctggaccgc cgcgctttcc tgagatcgca gcagaatcag cgagctacag cggagacaaa 44220
tctagcggct ggcaacaatt cacaatcagt ggctacgtca ttagacacca atagcaaaaa 44280
ctacaatcag cacgccaaac gcagcgtgtc tttcaatttt cccagcggta cgtggaaagg 44340
cggccagaaa accgcgtcca acgacacatc cacaaaaatc ccccatcgac tctcacaatc 44400
gcatcataac ctcagcgggg tatgagcttt cctgttactt tattcagaaa gcaccagaac 44460
ccgtcgccat ttcccctcat atacggtaca cgtccccctg atctgtcatc acggtacaca 44520
gatttcgccc gactgcggac gccgacggcc aatcgcgtgg cgtaggagtg gcgccccggc 44580
ttcattataa cgccacgtcg gagcccctgc gcgccacaac gccgtccggc gcaacttctg 44640
tctcggcacg gtacgataaa aacaacgtcc cccgtcgacg ttgttttctc cgagcggtga 44700
tcgttcccgt ccctctcctc cctccgcggc ccccacggcg gcggcctgct cgcacggacc 44760
tatactatta ccgccccacc gccgtcgtcg tcatgaactt catcatcacc acccgagact 44820
tctccaacga cgattcagtc ctgcgagccg ccgagatgcg tgacaacgtg gcaggctcga 44880
tttccaaagc gtacaagggc acggtacgcg ccgaaggcaa gaagaagctg ctgctgaagc 44940
acttgcccgt gccgcccggc ggctgctcgc gccgcaacag caacctcttc gttttctgca 45000
ccgagcgcga ctaccgcaag ttccaccagg gcatcgcaca gctcaagcgc gcgccggccg 45060
aactggaccc ccacgagatc cagcaagtca cggccagtat ccgctgccgc ctgcagccca 45120
gtctccgcga gccgcccacg ccggccgacg agctgcagac ggctgtgtcg cgcgtgtgcg 45180
cgctcttcaa ccagctggtt ttcacggccc agctgcgcca ctactgcgag caccaggaca 45240
aggtggtgag ctacgcgcgc gacgagctga ctaaacgctg cggcgaaaaa tcggcgctgg 45300
gcgtggaagt gcatcaactg gtagccctgc tgccacacga gcgccaccgc gaactgtgcc 45360
acgtcctcat cggcttgttg caccagacgc cgcacatgtg ggcgcgctcc atccgtctca 45420
tcggacacct gcgccactac ctgcagaaca gcttcctaca cctgttgatg aactcaggtt 45480
tggatatcgc acaagttttc gacggctgtt accacagcga ggcctaccgc atgctcttcc 45540
agatcggtca tacggactcg gtgtcggcgg ccctggaact ctcacacggc gcggcggccg 45600
ggccgcccga ggccgatgaa aacaacgacg agggagagga ggacgacgac gagctccgtc 45660
acagcgaccc ggcgccgctt cacgagtcca agaagccccg caacgcccgt cgtccccgca 45720
cacgcgtgcc gcctcacgag caaaagcccg aagaaaacga ggaggaagaa gaggagctgt 45780
ttccctcctg caaggcaacc gcagcattcc tgcgggcaga accctccgtc tccaacgacg 45840
acggcaacgg cggcgaacgc tgcgacacgc tagcgaccgc cctgcggcat cgcgccgacg 45900
aagaagacgg acctctagcc agccagaccg ctgtgcgggt cgccgcgacc ccctcacctt 45960
cagtcacccc agcccttacc cccgtcacgt cccccataac cccgttgtgt atttaacgtc 46020
actggagaac aataaagcgt tgatttctca agttccgctc tggttttggt ttcgttttca 46080
aagggagccc catcatggcc caaggatcgc gagccccatc gggcccgcca ctgcccgttc 46140
tccccgtgga cgactggctc aactttcggg ttgatctatt tggggacgag caccggcgcc 46200
tgctgctcga aatgttgacc cagggctgct ccaactttgt ggggctgctc aactttggcg 46260
tgcccagccc cgtatacgcg ctggaggccc tggtggactt ccaggtgcgc aacgctttta 46320
tgaaggtaaa gcccgtggcc caggagatta tccgtatctg catactcgct aaccactacc 46380
gcaacagccg cgacgtgttg cgggacctgc gcacgcagct cgacgtgctg tactcggatc 46440
cgcttaagac gcggctgctt agagggctca tccggctctg ccgcgctgcg caaaccggcg 46500
tcaagcccga ggacatcagc gtgcacctag gcgccgacga tgtgacattc ggcgtgctaa 46560
aacgagcgct ggtccggctg caccgggtac gcgacgcgct ggggctgcgc gcgtctcccg 46620
aggccgaggc gcgctatccg cgcctcacca cctacaacct gctgttccac ccaccgccct 46680
tcaccacggt cgaggcggtg gatctgtgcg ccgagaacct gtccgacgta acacaacgtc 46740
gtaaccgacc gttgcgctgc ctcacctcca tcaaacgccc gggctcacgc accctggagg 46800
acgcgctaaa cgacatgtat ctgttgttga cgctgcgaca cttgcagctg cgacacgcgc 46860
tggagctaca aatgatgcag gactgggtgg tggaacgctg caaccggctt tgcgacgcgc 46920
tttacttttg ttacacgcaa gcccccgaga cgcggcagac tttcgtcacg ctggtgcgtg 46980
ggctggaact tgcgcggcaa cacagcagtc cggccttcca gccgatgctg tacaatctgt 47040
tgcagctact gacgcaactg cacgaggcca acgtgtacct ctgcccggga tatttacatt 47100
tcagcgcgta caagctgctg aaaaagatcc aatcggtctc ggacgcccgc gagcgcggcg 47160
agttcgggga cgaggacgaa gagcaggaga acgacggcga gccgcgcgag gcccagctcg 47220
atctcgaagc cgatcccacg gcgcgcgagg gcgagctctt tttcttctcc aagaacctgt 47280
acggcaacgg tgaggttttc cgcgtgccag aacagcccag ccgctacctg cgccgacgta 47340
tgttcgtgga acggcccgaa accctgcaga tcttttataa cttccacgaa ggcaagatca 47400
ccaccgagac gtatcacctc cagcgcatct atagcatgat gatcgagggc gcctctcggc 47460
agacgggcct gacacccaag cgcttcatgg aactcctcga cagagcgcct ctgggccagg 47520
agtcggaacc cgagatcaca gaacatcgcg atttatttgc cgatgttttt cgccgtcctg 47580
tgaccgacgc ggcttcttcg tcgtccgcgt cttcgtcgtc gtcctcagca tctccgaatt 47640
ctgtttcgct gccgtctgcc aggtcgtcat ccacacgaac caccacgccc gcgtccacgt 47700
acacctcggc cgggacttct tctaccacag gtctcttgct ctcttcttcc ttgtcggggt 47760
cgcacggcat tagctccgcg gacctggagc agccgccccg gcaacgacgc cgcatggtca 47820
gcgtgaccct cttttcgccc tactcggtag cctacagcca ccaccgacgt caccgaaggc 47880
gacgcagccc gccacccgca ccccgagggc cggcccacac acgcttccag ggacccgaca 47940
gcatgccgag cactagctac ggcagcgacg tcgaagaccc gcgggacgat ctggccgaaa 48000
acctacggca tctctgaaag cggtttttcc tctttttcta cgtgtctgtc tcaagatgag 48060
acgtcgatat caataaaaat accgtcgacg tggttttttt aacagtgtgg ttttctttat 48120
tgactagcga agtacacagt ttacgagtag aaaagacagg gaaaggttat ataaaatgct 48180
gtattatata caaaaacatg cacataaaca aacgggacca tcgtgctcat catcccctcc 48240
ttgatcagtt gttcatgtaa acgtgtggcg gggtgagggg cggcatgccg ttggcggcgc 48300
cgggaataat gtgccgtcga ccgacgtcgc acaccttgaa acgccgtcgg cgcacgcagc 48360
ggtcgcagga cgggatatcc cagaggaagc ccatgtaggt ctcggggtcc tcgtcgtgaa 48420
agcggtagga gagttcaaag tggtgcaacg agcccgtccg agctcgcagc ttctggcgaa 48480
caccctccac gtcatcggtg cacagcgaca gtgctgggct gtcacacagg gcctgaagct 48540
cctgcggcca caggtgcgtg gccaggggcg agtccgtcgt caccagtttg acgcagtgca 48600
tcaggttctc ggtgatggcg tcgtacaggc gactctcagc ctcctcgtgc gtcatcacgt 48660
ttcgaggcag cgacagctcg tcgtcgtcat cctcgtcaaa catgatcatg gggtcagggg 48720
tttttttggg atgttgacag gtgggtgtct tttccagacg cacgatggcc tcacgccggc 48780
cgctgaaacg gtggtttcgg tgtcccttct ttcccatgac gcaggtgaac ataaccacgt 48840
cctcggccaa acggtagacg gcgtccatgg cggggtcgta gccgtagacg acgccgaaag 48900
tgtccaccaa gacgtactgg cgtacgagga actctttgcg ttctggcacc tcgtggccca 48960
gcgcgcccaa caactggtgg taacaggtga tgcgcggcac ggtacggatc atgagctcca 49020
tggtctggat gctgccgccc gcgcggacga cgctgaagga tgtttccttg aacttcataa 49080
cctctgtgtt gtgggtccag aaggcgaaat gggtgtcggg acactcatcg aaagggtcgt 49140
cgatggtgta ggaagcgtag cctcgcttgg tcacctcggc cgacaggctc tccacgtcac 49200
cgcggtagag catgacggcg ttccagtagt cgtcgtactg caccatgggc cgctggtagt 49260
cgcgcatagt gtggaagtgg tcgcggtgac gaaagccgtt ccgcagaaag tccttcatgg 49320
tgggtgccag ctcgtagacg cagtcgcgca ggtcatcgta gcagtagatg ccgccgcgct 49380
gcccgatgag cacgatgagt tggtagcgca taaagcccgg accctcgacg aagccaaagg 49440
ggtgcaggta ctcctgacag cagacgtaag cacctggtag agaatagaaa aaatccacgc 49500
acgttgaaaa cacctggaaa gaacgtgccc gagcgaacgt cctctttcca ggtgtcttca 49560
acgacgtggg gcttaccttg cgaacagacg gtgcccatct tgcccacgaa gggccccagg 49620
gcgctgcgcg aacggagctg gatgaagcag cgttcgggcc aggccacgtg cagccgggtg 49680
ccgcattcct gctccagaaa gtcgttgaga ccgttaaagt ccccggctcg gatggcgatg 49740
cagccgtagg ccatcagcgt gtcccgtagg tcgtccatga cggactcctc taccttcgct 49800
cgccgacgct gcgcttctcc agccaccgct gcggtcgaca gactcctccg tccgccttcg 49860
gagaactacg gcgcggcggc acggccttta tagacactat cagcgttgac gtcagacgat 49920
ccgatgaacg tcgttttttg tgctggaact tccctcgtcc cgacaaatgt agcggaaatc 49980
ttcaagcaaa tcgcgacgaa gtccgatgag gaggatgcaa aagaggctga gcaacgcgat 50040
gctgcccgcc gccacagtac atatgctcaa caacgcccag tgtcccaagg cgcgactttt 50100
ggctcggagg agagccgaac ggcggtttct ccacatgacg gacaacgtgg tccagtacgt 50160
ccatcctttg cattccggtg tccagacggg aagcgttgtc atgttatttc ccgtaactgt 50220
cacgttatgt tttgttttgt ttctcgtgag cttaacggtc ctcttgagaa atcgcgggca 50280
catgtcttgt agaaagatat aatcactttc cgcgtatttc gtcagtgttg acatcacggt 50340
ggtagtgttt tctgaagaag tagcgttgtc agtgacgttt gtttcttccc aacgtacgta 50400
tgattcgaac ggactcgtgt gcgctattgc ccgcaacacg tagctgtggc cggtgaagtt 50460
gagcgtcagt tgtcccacgg tcacgttcgt gtcattccta aaacatgcta cttctccgtg 50520
aacttccgtg acgtttatct cacgactctc gttcaagaca cgcaggggaa accagccttc 50580
caggtgatac tgaaaaccaa atttaagcat gacgctgtgc catttccgtc gtgattgatt 50640
aaacgttaca ttcaagggca gtctggcttc ggtcccgaga caggggccgt tgtagatttg 50700
cgtgtgattg cgtgtgcagt ttaggtggca gttcatgctc gtggtgttgg aagtgcgatt 50760
aacgtccgta ccgtggtacg tacatcggac cgaaacaccg tgtcccgtgc tccaaagcag 50820
cgtcaacaac agccacacag aaacctacgt ggagacgaca cgggactttt tattgacgga 50880
gactcacgtt tctaccctcc cctttcccgt aggtaaaaac ccacgtttat cacacacgtt 50940
gtttttacct gaaacccgcg cagcccgtgg acgcgacaaa aaaccgcggc actagaaaga 51000
aaatgaaaca agtatgttta ttaagcagca tgtggggcta atagggggga taactgaggt 51060
atagcaacta tgaaaaaata ctacaaaaaa aaaagctgaa catggtcatc tagcagcaaa 51120
gttctccttc tagaccacga ccaccatctg taccacgtcg ccctccccgg ccgtgtacac 51180
gacatccttc accacgaccg gcggcagcgg cggcgacgag gacaactcgc tctcgacgga 51240
ggccgggacg acagaggacg ggggggtggt ggcggcggag gacgaagggg tggcggcggc 51300
agcgggatct tcttccgaca cgggcaacgg caggctcggc ggcgcggaca gcacccgttg 51360
cgccggggcg tgagaaggct gagccccggt ggcctggatg tgggccaacg aattggctcg 51420
cagcgagtcg cgatccacga aggtcatagg aattttccct tcgcggatcc gccgctcaga 51480
ttccaggatg gcgcgcacgt agctgttcac cgacttggca aaagtgcgcg gcccctccgt 51540
attcttgtcg cgacgcgctt ccagcacctg cttttcgtag tccagctggt ggaagaccat 51600
caccaggtcg tccatagtgt gcgcgtgctg acggacgtgg gagcgcacct ccaccgggaa 51660
caaagcgttc caatactcca gcacgatagc accgtgccag aactgcgcca tgctgggcgc 51720
caggaaaaac aggataccgg agtcgtaggc gaacacgtcc cacttgggcg tcatgaacaa 51780
caccagctga cgcgtgggcc gcaccgaagc ttcctcccag gcctcgatga ccccgaacat 51840
gatgagctcc tggtccaacg gggggcagtg tcgctccagc caactgatct tgctcaggtt 51900
catctgcaga aactcgtacg aagggtcgca gatgcacacg tagagacccg agtcgtgccg 51960
cagcctggct ccgcgcttca tcagtttcct caccgcgtag cgaagcgcca ccttgcccaa 52020
cgccgacgcc tggatcagtc cccccacgtc catctgcgtc tgtcgccact cggcctcgtc 52080
cagcaggctc atgatagcgg cagtgctatg cgtggtcgta gtcatccttt ctatccttct 52140
ctatgaatag cagcaatagc ggtaaagtcc cttcttatac tatcccggag tctgtggttt 52200
ttttgtttac ccctgcttac tggtgagact gctgggggcc gttgtgctgc agcatccgag 52260
ctcgttgccg ccgttgccac aggaaccggt gtctccgcag ggcctttttg agggcttcgc 52320
aggcttctcg cgcaagtcct gagaggccct cggcgtcgat ggggttcacc tcgggcgtcc 52380
gagcctcgtt ttcttcttct tcatcctccc tttcctcctc cgtgtcctcc cgctctgtgt 52440
cctccgttac gctctcctcc ccggcctcgg ccaagagcgc ggccaccaag tccacggacc 52500
gctcggtctc cgagttctca ccgtcaatta cgccatgttg gcggcgtaac cggtgccgag 52560
aacgccgggt gagcgcacat gcttttttct ttcttaacca aggcgggaga ggatcttcaa 52620
ggcgttttcg ctggatccag cggtagctaa agtaccaaaa ggccagcagg cccacgctac 52680
ctaacagatt cacgtagact ggagacataa ttaaagaaag aagtgaaacc cgcgtgtggg 52740
tctcacgtcg tcttgaaaca ccgtcttata tacatgaaga tgccggacat gacgcgccca 52800
agacacgtgg ggttttcccc ttaggcgacc cggtttctta agatgttttt catcttcgca 52860
cgcgatgtac tacatcaaag ggtcggctga ccgaccgcat tgacgcacag tttccgagta 52920
cgcgcgtctc ggagcacctg acggtgagcc acccaactca cgcggatagg ggacaacact 52980
gacgtgaggg gcgattcacg tcactgacgg gaataagacg ggtgagggat ttccaccttt 53040
ttcttaagtg tgactctctt tacggtaaat cgcacctgtg acctcttaac ccctcctccc 53100
tggtacccga taaccgtgaa aaacacacac cacacgtcac gacaccgatc gattttcttt 53160
attcttagtg tgatgatagg taagggcact cgtgaggatg tgcaattatc attatcaagc 53220
ctttttcaag gcgtagtgat gatcgttggg cagaaccccc aggctcctag cgatctggga 53280
atagaaggag gagaacgagc ccagggccag aatgcccaca gtgtacatgg cccaggtctc 53340
cagaccgaac gtggcgggtc gcagcttcag atggtaggcc acccgctccg agagttgtga 53400
atgctcgttc aggcaacagg actgcaggtg ggtgagccca aaagcgcttt cgtttacgcc 53460
gcgcacgtgc accgtctggg ccgggcaatc ctggtgttgc gcgcgaaagt ggtcctgaca 53520
ggaaattccg tctacgtggc ggcgcgtgtt gttacccact tcgatcaaca acgtgttatc 53580
ggcaggatga tgcgagaacg cgacgacggt gttgttggag gtctggcggc aacagtacac 53640
gtcgagcgtc atgagggcca tgtcgccttg gtggtacacg gcgtacgccc aaccctggaa 53700
cacgagcgga cataacggac cgtgagcgga cgtcacggcg gcggttgtta ccgtcgtctc 53760
ggcaggagaa cacaataaac tcctgatcct catacacagg agtccaaccg tcagaattaa 53820
agtccgcgga gccataaccg cgcaagtgaa gccgatacga gtgttgctga atttgttcat 53880
tctgccgact gttgctcacg agcgttcgga ggcggtgcca caggctgttg gccattaaaa 53940
agtcctggcc cgaatgacga caagacagag cccgaggcga agaaaaaggc gcccgtcatg 54000
aagacgtagg caggggaatt cccatatttt tatggcttct tttaaaagtc tgtatccgac 54060
tccatccggc gcttttccca aaccgtggtc tcctcgtcgt ccgactcggt acccaggagg 54120
tggtaagtct tttgccgcac gtagaaagct ttcaacgtgg agcaaaagat gagaataaag 54180
accccgaaaa cgaaacaaac cacgccgatc atgccgatgc agacgttcat gtcgacgtag 54240
ccggcggtgc tgttggcggt gcggcaaaag agtgtcatgt cgtgcgtgca caaaaaacaa 54300
cacacaccac aggccaggtc gtagcgtagt tattattccg tagcagcaat gatggtacag 54360
tcaagcacat gctctatccc cgttaccccg atgatgcttg cgtccccgtt gttatattgg 54420
cactgtcccg gttaatcacc acggtgaaca ccacggccaa gaaaatgatc cctaatatag 54480
cgaccactaa gagagcaaaa gtccatttcc agccgttgtc aaagtacgcc cccgtggtgg 54540
gatgcatggt ggcgggcatt tccatcatgt ccatgtcgaa cgtgtgtcgc ggcgacggcg 54600
aactaaccag gcagtacggg ggtcgatagg gcggtgggct gcagtcgggt ggtggcggcg 54660
gtggcgtgga aaccgtcgtc gggcacagac ccatggcctg ctcgtaggtg gggggcgcgt 54720
cgtcgtgatc ccggtcgcgg agcatcggcg tgggctccat gtcggtggca gtgacggcga 54780
cggtggtaac tgtggtggag acggtaccga cggcgtccgc ggttcacctt cgagcaaaga 54840
gccccttctt tttgcgcaaa cgacggcaaa acagttctct gggacaaccg gtggcgcggt 54900
aagcgggtgc cacgctttca gggtgggtaa aacagtcgcg ggcgaagcag tagttgttgc 54960
agaaccgcaa gaacccgacg cgaaagaagc ccaggagtcc gcgcgccaga aagtgcgcct 55020
gccgcgtctc gggatgcacg ccgaagacgg cgccgctctc gttcaccagt atggagatgt 55080
ccaggcgctg ctgcgactcc accggcacgg cccgcaccac aaatacctgc agcacgttca 55140
gcgagcacgt ctcttttaac cagttgccgt gggccggatc ctcgtaagtc tggctcccgt 55200
tcaagacgac cgtcgtcagc gcctcattac cgtctcgcca gctgaagatg gaaccctcgc 55260
gcttcatgca caggcgccac aaggccagca ggtcgcgcgc caacatgaac tcgcgaccca 55320
cgtcgccgcc ggtctcgaag cggacatagc ccagttcttc gcgcagcggc gcgtagttgc 55380
gcaggccctc ctgcacgaag ccgcggaaac cggaccgcga caccaggtac agcgattcca 55440
ccacgggcga gtagacgtag acgcgaccgc cttcgccgat gagtacgggt agcggtgggc 55500
ggccgatggc ttcgcaacga ctcacagtgc ccaccggcag caggaacttg tcgcagcaca 55560
ggaaggtctt ctccaaacct ttaatattga gatgtccaaa gtaaccaacg cgtaacaggt 55620
cgcagtaggt gaagaaccaa ccgtttggcc agctgagacg cagcaccgtg ccgctgacgc 55680
gacgaaccag cttctgcagg tccttgcgag cgtcggaggt gacagagcag cggaaggtct 55740
cgttaaccag ctcgacagcc agcgcgtcct ccagcgtgcg ttccttcatc tcgtcgttga 55800
tgctctgacg gcgccgccgg atttcgtcga aacgggccgc ggaggcggcg accgacgcgg 55860
aggtcgtccg aacgccctct gtgacgctgc cgtccggcca gtcaagaaag ctaaggctgg 55920
cgctgcgccg cctaaagtgt ccgatccgcg cgggacgtcg ctgagggacg gtggctggtc 55980
tgctggggcg ggtacggccg cgggtgtccg cggacacgtt agttatacac ggaattgagt 56040
cacgtggcac gttgccagct gaaaccgccg tcgtctccgc cggcgttttc tccatcacgg 56100
gaccgcgccg tgcgcgcgtt cccaggcacg cggcccgcgc tctagccgca cttttgcttc 56160
ttggtgttag ggacgaactc gaacgttaca gaatcctcgc tgtcgctctc ctctttcgcg 56220
tcgttgaagt aattgccgga gttgcgatcc aaaccgccgc ctcctcctcc tccgccgccg 56280
cccgatccac ctttggacgt caggtagctg gtgatcttgt gctgctcgta tttttccttg 56340
gaggaaagac cgtggtcgtg atcaccgccg ccgccaccgc tgctcatttt ccgcgtaccg 56400
gaaccaccgc cgccaccgcg gtcgtgcttc ttgccgccac cgccgccacc tcctcccaga 56460
ccgccgagac ccatgggctc gttcatgaga tcgttatcca gacccgggcc gtcgtcatgc 56520
agaccgccgg cattggccag cgaagagagg ctgccgccac caccgccgcc gccacgcgac 56580
ttgccgctgt tcccgacgta atttttgtcg aagggatcgc cacgctggaa aggttcctcg 56640
gtgagaaaat tctccacggc gaacagaccg ttgcggctgg ccacgtacaa cagcgtgtcg 56700
tgctccgtaa ctatacgcaa cgtgcacggc agtttggtga cggcgcaatt gagcagcgtc 56760
tggtagaagt tcttcagctg cacgttgata cgcatgtttt tcacgccgtg gaaactgacg 56820
cggttattgg ctgtgaattc cagctcgctg ccgttggtca ggataaactt gatggccggt 56880
ggaccggcgt gcaccagaat ctgcacggtg cccgtagggc agggcgcttt tttaacgtta 56940
cgcttgacgc gggtatgcgg cccgatccac ttaagcaggt cggccaccac gccgaaatct 57000
agatccacgt gcacggccga attctcgctt tcgcgcacaa tgtcttggcc gtgcacgcag 57060
gccgagctga actccatatt gaaatcgggc gcgcacatgg agatcttggc cgacaggtcc 57120
gagatgtcct gcacgtagaa cttggtcagg tccttgctgg aagtcaggta catgaaatta 57180
cccagcagcg gcgtggaatt gttaatggtc ttgggctgaa acgacttgtc agtgatgtag 57240
aggcatgagc tgttaaaagt gatttttgac acgcagtgac tgcgtaccgt ttgcaagata 57300
agcgacggcg tgggcaagaa ggtaaccgtg gtgttctcct tgagcgcacg gatcacagat 57360
cgcagctgct ggatagccgt cttgtacggc ttcagccgca gcgccagcgt cggcggctcc 57420
gagaggcgcg tcttgcgatc catcccggac agcgtgcaag tctcgactaa ggagcgggcg 57480
cgagcgagcg aaagttttat agagagcaca cacgacgacc gggaacgctg cgaagacgcc 57540
cggcgtctaa taatacagcc gcgccgagcc agcgggcccc cgactaagag gcacagtact 57600
tatatactcc gaccttaaag cgccagtggt accacttgag catcctggcc agaagcacgt 57660
cgggcgtcat ccccgagtca tagtagaaaa ccagggccac gcactggtcc acaaacacgc 57720
tcaggttcac ggccgccatt tccacgtcgt tttggatcgc cggtgccgcc tggaacagac 57780
actgcgtcgc cttgccctcc tcctggtgct gctccaacca cgcgtaattc accacgggca 57840
cgcgcagcgg cctccgcacc acggtgggga agtaacactc acggttgggc gggcacaatg 57900
accacaccgt ctcctcctcg aacacggtgc cgcgcgaagc ccacactgac ggcgtcacgc 57960
cccacagatg cgccacctcg tcgtcgggac ccaccgccag aaactgacag ttgcgcaatc 58020
cgaactcgag catgtcggcg cgcagcgctt cccagcgcgc gctggcgatg gagagccgcg 58080
gcaaccgata caattcgaaa atgaatttgc cctcttgata gatggtgcgt tcgaaccact 58140
cgcagcgcgg caaacccgac ttgcacaaat cgacgctagc gcgcaccgcg gcaaagtaca 58200
tgtgctcaaa gatgcgctcg atcaagtccc aagaggcaaa gtacgtgaac cctaaccgca 58260
tgagcgccgt gtgcaagcca gccacgccga tgtgcagcgg acgcagtttt tccagcgcgc 58320
tctctaccca ccattcggac gccgacatta gcgcgtccaa gcgcgcgttg ccccaaacca 58380
ccgcctcggt caccaactcg cgcagcacgc tcaaatcaaa gtaacgtcgc gtgttcccca 58440
aaaccacgtc gggtagatgc agcttctgct cgtcgctacg cgcaaacacg cagcgagcca 58500
cgttcaccgt cagccgctgc accggcatgt cacactcgcc aaagtggcac gacgccatat 58560
cgggactcaa gcacggcggc aggcacacgc tgtcggccat aatcgagtac ttgactacgt 58620
gatggacaaa gaccaccgag gcacggccct tgagcgcgca cagcaacatc tttttcagaa 58680
aatcgtccgt gttcacgacc accttggggc acgattgctc gcagcgcgaa tactctttct 58740
cgaaagccga ctcctgaccc aggtccgaga gccgccggga gacaggccgc ccaaacagcg 58800
agtagcgctg ctcacgcgca cggtagcgct tcattaacac gctaggcacg ttgaaagcgt 58860
agcaaacccc cgtcaactcc gacgtgcttt ctttgagaat aaagttaatc acgcggatag 58920
cggccacgtc ccacatgtcc acaaacacac gtaccacggg tcgatgcacc tccttctcgc 58980
gtatcaaatc gcagtatccc cccaggcaac gaatcacgct gttcacatcg gcgttaagtc 59040
gcgttacgtt caccgacaca gaaacgccgc aactcaaggt actcatccac ttgcacatgg 59100
ccgcccaact ggcgtcacgc gagaaagggt cggccgagat cagaaagtcg tactgcggca 59160
cgcgatcgaa acccacggta gacatggtga aggtggacag cgacagctgc ccatcgcgac 59220
agcgcttcaa caccgattcc aacacctcgc cctcgaaacg cgcatccaga tggaaacgat 59280
agatgcgcga gtgcctactg ttctcgatag cggccgtcaa cgccacggcg atgcgcaaaa 59340
acacgccgcc cgggctctcg tcctgtccgt gcagttggcg acacacctta tccaaacaca 59400
aaatggccgc gtacaagccc cagcaaccgg ccaattccac aaaacgcgcc gtctcctcgg 59460
ccagcttggg tagatcctcc atgtgacgca gcacaaaacg gcgcaccgac tcatcgcaca 59520
gctccgaagc gtaacacagt ggcgtgcggc tttcacgcgc ccagttggct ttgaaataaa 59580
agcgacccaa cagcaggtcg caacgcggcg agtgacgaat cagacaggga ccgtggcgca 59640
taatgagctg aaatagcctg aaactgccca aaccggcact gtgccgcgac acggtgtcca 59700
tctcgcgcca cagcgcgttc ctgtcggacg gcagctcccg cgccggctcc tgtacgccgc 59760
aaaagcgaaa cttgccccag tagccgtgac aatgacactt tttgcccatc aacatgcgcg 59820
tagcttgtat cggcggcgat actttgcaga gcgaagcccc gaaatcgtcc tcctcctcga 59880
cactgtccag ctccatcctg gtcgcgccgg ccggattaaa ggtgctcaga ccgctactca 59940
cgcgtccacc gcgactgggc acggcgggac cgctgtcacg cgtcaacgac agcacagacg 60000
gcgtgccgtc gggagacggc gactcgggac gccaactgac gacgccgcca ccactcgtaa 60060
aacccgctac acatgctaca ccgctcgata cgttggtatt tccagcggac gcttccttgt 60120
cacccccggg cagcggcccc tcctcgagct cgctgtcatc tcccccgata gtatcagcgg 60180
cgacctctgc cgacgattcc tccgtctcgg tttccgcgct gcggcttgga atcctacctg 60240
gccggcaccg atgtgcgggc accgaggaca cccgctgttc ctcgtccgcg tcagccggat 60300
tcataagttt acgaggaaaa taacaaagaa atcaggtaga tttcaataaa gtgagtctag 60360
atggcgccga caactacggt ttataaagtc tgtgtgcgat gtgttttttt cttctgtgtc 60420
tcctccccgt atgctgtcag cgccgctcag acgaattctc gaaagtctcc caattcgacg 60480
ctaaagttgt ccaaacggac gacggacagt ttgagttctt tgtgtaccag gaacgaggtg 60540
tgaatgtcgt cagccaggca ccagcccagc ttttgtatga ccccggtaca cagagggatc 60600
tggcgcgggc gcgtgatgcg acggttgaca aagctacagc gctcgcgggc gaactttccg 60660
cgtgcaacgt cgaccaaggt ctgccagtgt gcgatgctgg aggtgagcac gtagatgccg 60720
ggacgtgttt cgggcccgtc atagtcatag acgatgatta aatacacgta ttgcagccgt 60780
ccccgggtct cttcccacgt caggtacatg tctttcggta tcatcaacgc gaacacctcc 60840
gttttgagcg tgttgtaaag gtagccgcgc atgacgcagg tgagcaacga ggtgatgccc 60900
agcgagacgg tcttgacgca gcccagcgtc tcgaggcggc ggtgcagcag atgcgggccc 60960
aggtccagcc actgcagcgc ggcgcgcgcg gccgaggccg tgtacacgct ttcgagcagg 61020
cagcgcgtgc tggccgagac gttggaggcg cgaatgccta acaggtaaag gctaatgtag 61080
aggtgtcgcg gcgagtcgca acccgtctcc atgcggatga gcagcgcgcc cggctgcgcc 61140
tcgaactcta ccaggccctc gggcacgaag aaacgcgccg tgagcgcctg gtgatcggcg 61200
tggtagagat agcgaaccga tatagtattt acctcgcgtt tggctttgag cgccgtcact 61260
agttcattgt cctcgtcggc cgggtcgcgc ggccgtttgg ccaccgcgcg cgcgtccatg 61320
atggcgaggc gcacggtaga tttcaaaaag ttgatagagc agctgcgggc acgggccacg 61380
gacaaagcgg aggcgttaaa taccgtgagc caattggaga tcggcgcggt ggatgcccag 61440
gacgtgaccg cgagcgccgt gcgcgccttc gtgggtgcgt tgccgagctc gggctaccac 61500
tttggcttcg tgcgtcagaa cgtggtcttt tacctcctaa gccacgccac ggtacagacg 61560
gcgcgcgacc cgctgtacgc cgccgagcag ttgcacgaac agctggaccg cttcctgcga 61620
caccagcacg acggcggcgg agacgaggac cggttgccgt tctaccacaa cggggccacg 61680
ctgacggctt tccagaagct gttgcagacc ctgcgcgaga tccagaccgt aatagccgaa 61740
cagagcggcg gcaccgcggc ggcggcggac ttgatcgcca gtaacaacgc gtcgaccgag 61800
cgccgcggca agaagggcgg ttcgagttcc gggggccagc agccgctggt ccgccgggtg 61860
atcacgcagc tggaaacggc tgccacggag gcgcggccct acgtcaattg tcgcgccgtg 61920
gccgaactcc tggacctgac ctaccagcgg ctcatctact gggcctgcac gctcatgccc 61980
tacgtgttgt ttcggcgcga caccgacacc gaactggaca cggtgcttct gatgcatttt 62040
ttttacacac actaccgttc ggttaacggc gatttggccg tggagtttca aaactacgtc 62100
aagaacagcg tgcggcacat gagctctttc gtcagttccg atatcgacgg cgaccagaag 62160
cccggtgccg aacacatgcg tgacgtcagc tacaagctgt tcgtgggtaa tctgcaagcg 62220
cgtgacgcca gcggcctcat gtttcccatc attagcacgc gcatctccac cgtgaacctt 62280
tacctgtcgc ccgaacgtat gtttttccac ccgggtctga tctcgcgtct gttgagtgag 62340
gaagtttcgc cgcgcgccaa cctagacgct tacgcgcgcg tgtgcgatcg cgtgctggaa 62400
gaccacttgc atacgccgcg acgcgtgcaa cggctactag atctgacgca gatggtaatg 62460
cgactggtgg aactgggttt caatcacgat acctgcgcgg cctacgcaca aatggcgctg 62520
atccagccgg ccagtcagaa gagctcgctc tttgtcagcg agattcgcga gaaactcata 62580
cagatcatct acaattttta cacgtttttc atgtgcctct atgtgtacag ccccacgttc 62640
ctgttcgacc accggcggcg gttgattttg gagcagcatc gatccacgtt gatcggctcc 62700
aaggaggaac tacagcacgt ctggagcaac gtgacactga acgtcaatac gcactttgcg 62760
gttcagtaca cggaagaaga ctttgaggca catacgaagg gtgccacgga ggcggagcgc 62820
gagtacctgt atcgggacct gcacagcaag tggggcgtgc acctgtttac cttgcgtccg 62880
tctcgcggcg cggccggcgc ggcctcgcct ttgcctccgc ttgacggcgt cacacgctcc 62940
gacatcttac gcgaatgcgc gctcgttaat ctgaacgaag gccgcgtcaa ctacgcctcc 63000
ctgctagcct tcagccatca tcccgagttc cccagcatct tcgcgcagtt ggtggtggta 63060
actgagttct cggagatctt tggtatcccg cagggcctgt ttcaagccgt gggttcgccg 63120
cgtcttttcg cactcattca gctgtgccgt gtattgttgc ccgagcaggt gacgctgtac 63180
cagaacctgg tctccatcta caacctgacc accttcgtca agcacatcga cgccgcggtt 63240
tttaagacgg tacgcgattg cgtcttcgac atcgccacga ctctcgagca cctcagcggt 63300
gtacccgtca cgcccaatgt ggacctgctg gccgagctca tggcgcgctc cgtagcgcat 63360
aacctgtaca ccaccgtcaa cccgctgatc gaggacgtga tgcgcagcag cgccggcagt 63420
ctgagaaact atctgcgaca tacgcgactc tgtttcggtc tggcgcgtgg ccgggcgcgc 63480
ctctcggagg acggcgtgac ggtgtacgtg gaggtacaag gtcaatacgg actacgcgta 63540
cccaccacgc gtttcgtaga acagttgcgc gagctggttc gccgcgatcg gctgttggcc 63600
gagaatctgc gcggcttgaa cgagcgcctg ctgagtgttc gcgtgcgcgt acgtcagatc 63660
agcagcgaca cagaggaagt aagccgacac gccaagggtc accgcacggt ggcccagatg 63720
agcaaggcgc tcaaaaagac ggcctccaaa atcaaagtgt tggaaacacg cgtgacattg 63780
gcgctcgagc aggcgcaacg ttccaatggc gccgtcgtta ccgcggtgca acgcgcgcta 63840
gccgtctttg acgtactaag tcgcgagaac ttggaacgcc gcggcgcaca gctctgtctg 63900
acggaagcga cgagcctact gcaccgacat cgcgcgctag cgccgatgac ctggcccgcg 63960
ggcacgggcg ttgcggcggc ggccgaagcg gatcgcgcct tacgcgagtt cttggaggcg 64020
ccctgggaat cggcgcccca accgccgcga ctccgcatga cgcccgacac cgatcacgaa 64080
gaatcaacgg caggcgcgac gtccgtaccg gaggtcctgg gtgcgcgcta cgaacccgca 64140
cacctggccg cgagcgacct attaaactgg tacatcgtcc ccgtaagcca ggcgcagcag 64200
gacatcttgt cttcgatcga cccgcccgcc ggctcgacat cggtgtccct gccgccggcc 64260
tcgccatgaa agtcacacag gccagctgcc accagggcga catcgctcgc tttggagcgc 64320
gagcgggcaa tcaatgcgtc tgcaacggca tcatgttcct acacgccttg cacctgggtg 64380
gaacgagcgc cgtcctgcag accgaggcgc tggacgccat catggaagag ggcgcgcgtc 64440
tggacgcgcg gctagagcgc gagttgcaaa agaagctgcc cgccggcggg cggctgccgg 64500
tctacagact gggcgacgaa gtgccgcgcc gcctggagtc gcggttcggc cggaccgtgc 64560
acgcgctctc gcggcccttc aacggcacca ccgagacgtg cgacctggac ggctacatgt 64620
gtccgggcat cttcgacttt ctgcggtacg cgcacgccaa accgcgtccc acctacgtac 64680
tcgtcaccgt caactcgttg gcgcgcgccg tggtcttcac cgaggaccac atgttggtct 64740
ttgatccgca cagctccgcg gaatgtcaca acgccgccgt gtatcactgc gagggtctcc 64800
atcaggtgct gatggtgctc acgggcttcg gcgtgcagct gtcgcccgct ttctactatg 64860
aggccctttt tctctacatg ctggatgtgg cgaccgtacc agaggctgag atcgccgcgc 64920
gtttggtctc cacctatcgc gaccgcgata tcgacctcac cggcgtcgtc cgagaaagcg 64980
cggacacggc agcgacaacg accaccgccg caccttcctt acctccgctg cccgacccca 65040
tcgtcgaccc gggttgccct cctggcgtgg cgcccagcat tcccgtctac gatccctcgt 65100
cctcacccaa aaaaacaccc gagaaacgcc gcaaggacct cagcggtagc aaacacggag 65160
gcaaaaagaa acccccgtcc acgacgtcca aaacactggc caccgcctcc tcctccccct 65220
cagcgatagc ggcggcctct tcttcgtccg cggtaccacc gtcctacagc tgcggcgaag 65280
gggccctgcc ggccctgggc cgctaccaac agctggtcga cgaggtagag caggagttga 65340
aggctctgac gctgccgccg ttgcctgcca acaccagcgc ctggacgttg cacgcggcgg 65400
gtaccgaaag cggcgctaac gcggcaacgg ccacggcgcc gtccttcgac gaagctttcc 65460
tcaccgatcg tctccagcag ctcatcatcc atgccgtcaa tcagcgctcg tgtctgcgtc 65520
gcccctgcgg tccgcaatcg gcggcgcagc aggcggtacg cgcctatctg ggcctatcca 65580
agaaactgga tgcctttctg ctcaactggc tgcaccacgg cctggatctg cagcgcatgc 65640
acgactacct gagccacaag accaccaaag gcacgtactc gacgctggat cgcgcactgc 65700
tggagaaaat gcaagtcgtc ttcgatccct acggacgtca gcacggcccg gcgctcatcg 65760
cctgggtgga ggagatgctg cgctacgtgg aaagcaagcc cactaacgaa ctgtctcaac 65820
gactgcaacg tttcgtaacc aagcgaccga tgcccgttag cgacagcttc gtctgcctgc 65880
gacccgtaga ctttcagcgt ctgacgcagg tcatcgaaca gcgacgtcgg gtgttgcaac 65940
gtcaacgcga ggaataccac ggcgtttacg agcacttggc cggcctcatc accagcatcg 66000
acattcacga cctagacgcc agcgatctga accgacgcga aattctgaaa gcgctgcagc 66060
cgttggacga caacgccaag caggaactct ttcgcctggg caacgccaaa atgctagagt 66120
tgcagatgga cctggaccgt ctgagcacgc agctgctgac gcgcgtgcac aatcacatcc 66180
ttaacggctt tttgccggta gaggacctga agcagatgga acgcgtcgtc gagcaggtac 66240
tgagactctt ttacgacctg cgcgacctga aactgtgtga cggcagctac gaagagggat 66300
tcgtcgtcat acgcgaacaa ctgagctacc tcatgacggg cactgtgcgc gacaacgtac 66360
cgctactgca agagatcctg cagctgcgac acgcgtacca gcaagccacg cagcaaaacg 66420
agggtcgcct cacgcagatc cacgacctgc ttcatgtcat cgagacgctg gtgcgcgacc 66480
cgggcagccg cggctcggcg ctgacactgg ccttggtaca ggagcagcta gctcagctgg 66540
aagcgctagg cggcctgcag ctacccgaag tgcagcagcg cctacagaac gcgcaactcg 66600
cgctaagccg cctctacgaa gaggaagagg aaacgcagcg tttcctcgac ggactctcgt 66660
acgacgatcc gcccaacgaa cagaccatca agcgacaccc acaattacgc gagatgttac 66720
gtcgcgacga acagacgcgt ctgcgactca tcaacgccgt actgagcatg ttccacacat 66780
tagtgatgcg actggcgcgc gacgagtcgc cgcgaccgac gttttttgac gccgtcagtt 66840
tgttgttgca gcaactgcca cccgactcgc acgaacgtga ggatctgcgt gccgccaacg 66900
ccacgtacgc gcagatggtc aagaaactgg agcagatcga gaaagccggt accggcgcat 66960
ccgaaaaacg tttccaagcg ttacgggagt tggtttactt tttccgtaat catgaatatt 67020
tctttcaaca tatggtcgga cgactgggcg tcggacctca ggtaacggaa ctctacgagc 67080
gatatcaaca cgagatggaa gaacagcacc tggaacggct agaacgtgaa tggcaagaag 67140
aggccggcaa gctcacggta acttctgtgg aggacgtgca gcgtgtcttg gcccgggcac 67200
cgagccatcg tgtcatgcat caaatgcaac aaacgttaac caccaagatg caagactttt 67260
tagacaagga gaaacgtaaa caggaagaac agcaacggca gctactggac ggctaccaaa 67320
aaaaggtgca gcaggatttg caacgcgtgg tggacgccgt taagggcgag atgctctcca 67380
ccatcccgca ccaaccactg gaggccacac tcgagctgct cttgggccta gatcaacgcg 67440
cccaaccgct actagacaag ttcaaccagg acttgctgtc ggcgctgcag cagctgagca 67500
aaaaactaga cgggcgaatc aacgagtgtc tgcacggcgt gctgacgggt gatgtagagc 67560
ggcgctgtca cccgcaccga gaagcggcta tgcaaaccca agcctcgcta aaccacttgg 67620
accaaatttt gggtccgcaa cttctgatcc atgagacgca gcaggccctg caacacgccg 67680
tccatcaagc gcagttcatc gagaagtgtc aacagggcga tccaactaca gccatcacgg 67740
gcagcgagtt cgagggcgac tttgcacgct accgcagcag tcaacagaag atggaggaac 67800
aattacaaga gactagacaa cagatgaccg agactagcga gcggctagat cgctcgctgc 67860
gccaggatcc cgggagcagc tccgtcacgc gtgtacccga gaaacccttc aagggtcagg 67920
agctggcggg tcggatcacg cccccgcccg ccgacttcca gcagcccgtt ttcaaaacgc 67980
tgctagatca gcaggccgac gcggcccgga aagcgctcag cgacgaggcc gatctgctga 68040
atcagaaagt acagacgcag ttgcgacaac gcgacgagca gctgagcacg gcgcagaacc 68100
tgtggactga tctggtcacg cgccacaaaa tgagcggcgg actggacgtg accacccccg 68160
acgccaaggc gctgatggaa aagccgctgg agacacttcg cgagctgttg ggcaaagcca 68220
cgcaacaact gccgtacctg tcggcggaac gcacagtgcg ctggatgctg gcctttctgg 68280
aggaagccct tgcgcaaatc accgcggacc ctacgcaccc gcatcacgga agcaggaccc 68340
actaccggaa cctgcaacag caagctgtcg agagcgccgt gacgctagcg catcaaatcg 68400
aacaaaacgc ggcctgtgaa aattttattg cacagcatca agaggcgact gccaacggcg 68460
cgtccacgcc gcgggtcgac atggtccagg cggtggaagc ggtctggcag cgactggaac 68520
ccggacgcgt agccggcggc gccgcgcgtc atcaaaaagt gcaggaactg ttgcagcgct 68580
tgggtcagac gctaggcgac ctagaactgc aggaaacgtt ggcgacggaa tactttgcgc 68640
tgttacacgg aatccagacc ttcagctacg ggctggactt tcggtcgcag ttggaaaaga 68700
tccgcgatct gcggactcgt tttgcggaac tggccaagcg acgcggcacg cgtctctcca 68760
acgagggagt cctgcccaac ccccggaaac cgcaggcgac gacttcactg ggcgccttta 68820
cacgcgggtt gaacgcgctg gaacgacacg tccagctggg tcaccagtat ctgctcaaca 68880
agctcaacgg ctcatcgcta gtctataggc tggaagacat tcctagcgtg cttccggcaa 68940
cacacgagac cgaccccgcg ctgataatgc gcgaccgcct gcgtcgccta tgcttcgcgc 69000
gtcaccacga caccttcctt gaagtggtag acgtcttcgg catgcggcaa atcgtcacgc 69060
aggccggcga acccattcac ctggtcaccg attatggcaa cgtagccttt aagtacttgg 69120
cgctgcgaga cgatggtcgg cccctggcat ggcggcgccg ctgtagcggc ggaggactca 69180
agaacgtcgt caccacacgt tataaagcca tcacggtagc cgtggccgtc tgtcagacat 69240
tgcgcacttt ctggccacag atctcgcagt acgacctacg accctacctc acgcagcatc 69300
agagccacac gcaccccgcg gagactcaca cgttgcataa ccttaagctc ttttgttatc 69360
tggtgagcac cgcctggcac cagcgcatcg acacgcagca ggagctgacg gccgccgatc 69420
gcgtaggcag cggcgagggt ggtgacgtag gggaacagag accgggccgc ggtaccgtgc 69480
tgcgcctgag tctgcaagag ttttgtgtac tcatagcggc tctgtacccc gagtacatct 69540
acaccgtcct caaatacccg gtgcagatgt cactaccctc cctcacagct cacctacatc 69600
aggatgtgat acacgcggta gtcaataaca cacacaaaat gccccccgac cacctccccg 69660
aacaggtcaa ggccttctgt atcaccccca cccaatggcc cgccatgcag ctcaataaac 69720
tgttttggga aaataaactg gtacagcaac tgtgccaggt aggcccgcaa aaaagcacac 69780
cgcccttagg caagctatgg ctctacgcca tggccacgct ggtctttcca caagacatgc 69840
tgcagtgtct gtggctagaa ctgaaacccc agtacgccga gacatacgcc tcggtgtccg 69900
aattggtaca gacgttgttt cagattttca cgcaacaatg cgaaatggtg accgaggggt 69960
acacgcaacc gcagctcccc accggagagc cggtgcttca gatgatccgc gtgccacgtc 70020
aggacacaac caccacagac acaaacacga ccacggagcc gggactttta gatgttttta 70080
ttcaaacaga aaccgcccta gactacgcgc tgggctcctg gcttttcggc atacccgtgt 70140
gtctcggcgt gcatgtagcc gacctgctga aaggccaacg tatactagta gcgcgccacc 70200
tcgaatacac gtcgcgagac cgcgacttcc tccgcatcca acgctcccgg gatctcaatc 70260
tcagtcaact gctccaggac acgtggaccg aaacgccgct ggagcactgc tggctacaag 70320
cccaaatcag acggctacgc gattacctgc gtttccccac ccgcttagag tttattcccc 70380
tagtcattta caacgcacag gaccacaccg tcgtacgcgt gctgcgaccg ccctccacgt 70440
tcgaacagga ccacagtcgg ctggtgttgg acgaggcctt ccccaccttc ccgctgtatg 70500
accaagatga taactcatcc gcggacaaca tcgctgcgtc tggcgccgct ccaacaccgc 70560
cggtaccttt caaccgcgtg ccagtcaata ttcagtttct gcgtgaaaac ccgccaccca 70620
tcgcgcgagt tcagcagccg ccgcgccgac atcgtcatcg agcggccgcg gccgcagacg 70680
acgacggaca gatagatcac gtacaagacg atacatcaag gacagccgac tctgcattag 70740
tctctaccgc ctttggcggg tccgtctttc aagaaaaccg attgggagaa acaccactat 70800
gccgagatga acttgtggcc gtggcgcccg gcgccgccag caccagtttc gcctcgccgc 70860
ctatcacggt gcttacgcag aacgtcctca gtgctctaga aatactgcgg ctagtgcgat 70920
tggacctgcg acaactggcg caatccgtac aggacactat tcaacacatg cggtttctct 70980
atcttttgta accgacactg acagtagcgg gtaataaaaa caataggatt tttatcgttt 71040
ttttatgtta caaaacaacg tatcactttc acggtgattt attcttgcta ttccttttcc 71100
ccttgggctg tcagcgccgg gtgcgcgaca cggctaccat gcgcaacagg tccagcttaa 71160
aggcgcactt gtcattaaac aggctggaca tgcgcgtgta cttgctcagc atggtggcca 71220
acaccgggtg ggtggcctct gatatctcgg tcggcagctc caaaacgacg ttaacgacgt 71280
gacggtgttt ttcgtcccgc ttgttggcca ccgtgggtcc cggcgcggtg ttagacatgg 71340
ggcaggccgt ggggggagga cgaagaggaa gccgctgcta aaccgccgcg cgcctgctgc 71400
acaatgtggc cgccgacgtg gcaggcggtc tgtttaacca gcgcgcagcc ccgacacagc 71460
ggggcgccgt cctcgctttc caaacagctg tcgcggtact cgcccgtctg acagcgcgcg 71520
cacagcaggc cgtgcccgtg cgaagtgagg cgcaggagac gcgggaccgt cacgtcgcgt 71580
accaccacag tggagtcgca ggtgcgtgcc gcgcagggca gaatgacgtc gaaagccagc 71640
cggtgatcgt acacggcaca agccgcgttg aggcccagca cggctttcca gcccacgcgt 71700
acgcagcgct gtccaaagag cgtctcggag acgagctcgt agacgcgctg ccgcaccacc 71760
cgctgactgc cgcagagcga gcagtgcacg agctcggcgt gcgtgttgaa gatgacgctc 71820
ttttcttgac ggtcccgata atagaacatc gagttgagcg gaaagttttg ctggcagtgt 71880
agcttttcct tacccaggtt gaggcagtgt ccgcactgcc gacagaccac ggccaccagc 71940
gagcgcgcgt ccagatggcg ctcgcacttg agtcgacaca gacaccagag cggcaggtcg 72000
atgacgctgc cgatgaggcc gccgcgcagc gcggcgctga gtgcaaagag gacgatcttg 72060
gtgggctcta cgtgacgcgc ctgctgtccg gcgcccgcgt gtcctaccgc cgcagctgcc 72120
gccgtcgagc ctcctccgcg cgtctcgtcg tgcagaccca gtgcccgcaa cggcaccagg 72180
tatcgcggac acgtgtcgca aaacgtctgc accgcttgtc gggccagtac gtagagcggg 72240
tttccgcagg gtaccttccc ggcgtaccgg cgcaaggctg cgatgaggcc ccgcaactgc 72300
ggcgaccgcg gctgccgttg gtgacaccac tggttacggt ggtatacggc caaatcagcg 72360
cgggcgtcga agcgcttggc gcgtagtaat gctaggcacg gcgagctggt ggggtgaagc 72420
acgggcagcc gaaggtccac cccgaaaagg aaacggtgaa ggtcacctag cagcgaggcg 72480
gtgacaccgt ccaacaacgc gtgcagccgc tcgggcgggt agagccgcag acggcgcagc 72540
aggtagtcgg tgtcgtagcg ttcgaaacgc agaaaggcca tcgtgcggac ggccacggtg 72600
tgcagacagt ccatgctgta gacgtaagcg agaaacacaa agtagggctt ggtcataacc 72660
atacgctgaa agagcgccgt caccgcctcc cgctcggctt gccgacacac cagccattcg 72720
cgcaggaagc gttggtagag acggtcgccc agctcgcgat tcagaaagcg cttatccgtc 72780
acgaagagat gaaggacgca agaacgtggc acgtgatgca ccagctgctg ctggaggacc 72840
gccgacgtct gcgccgcaaa ctgcgccggt ggctgcgacg tttctaccgc cgcttcctcc 72900
ggctgcagcg caccgcggcc gatcaccagc tgcacatgga aatggtcctc gtgaacgcag 72960
aggggcgcga agagacggcg cagagcctgg tggaactcat cagtcgcggt gtgcggagcg 73020
tgtcggagac gacgactggc catgaccgcg ccacagcaga gccagcacca gcagaagagc 73080
cagcaccagc gggcccagag tcgcaaagcg cgcgggcagc cacggcccag actgcggtcg 73140
cgatggcccg gagcgcgctc gccaccacga tgacggtgcc caacgataac cagtccgctc 73200
caaggacggc gcgcacggcg gagacggcgg atgacggtga tgggtcgaca cccctcgccg 73260
acgactcacg tgctcctcca gaggccgacg cgcggaccct ccgacgtcct ggcccgccgc 73320
tgccgctgcc gccttccctt ctcccgccag agccagcaac tcctcctcct cttcatcagc 73380
gtctccctcg cttgcgcatc cgcatcgtcc catacaggcc tcacaacgac acagccgcca 73440
cgaccccgcc gccatgggtg gcggcggcgg ccgaggcccg gcagcggcgc cgccagcggc 73500
gaccatggtg ggagagcaac tcggatgacg aggaggagga gggggagatg cggtccgaga 73560
ggaccgcttt cccgccgttc gcgtaagcgc ggccgacatg cgggcgcgcc acagggacgg 73620
accgctgccg ctgtgactgc ttacggtgac gtggttccgg accgccaacg acgtcgacgc 73680
ggctttcttg gcgtacagct cgcgcagcag attctcgtac tcgccctcgt tttcgggtcc 73740
gaaggcgatg agctcgatgt tgaagaccga cgccgaattg gatttgcgca ccacgcactt 73800
cgtcagcact ccgtaggccg agggcttgat ctcctcgatg tccttgagcg tgacgatgag 73860
cgactcgttc accttaagca cattgaactc acctacgtgg cgcgccggcg aaacgagctt 73920
gacgggcgct cgtacaaaac agcagaggga gacggcgcag ccagtgtttt taaagataaa 73980
acaaggcacg tggtctgtgc ggctctccca gtagctgagt agatactcga cacaatagac 74040
cgtgtctgtc ttgagcatgg cgtcgcacac cgagtaattg gggtttttac agatgaggcc 74100
ggcatcggtg acgcgcagct cgctgggacc caacttgagg atacgccgcg tggcctgcac 74160
cagatcctga tggagaacct tgttcatctc catcgcaccg acgccaccgc cgatttattt 74220
acccggcgcc gactcgtctt ttccctccag gattccgtta atgtccatga gcttgctgac 74280
gatcgccgtt aatagttgcg tcttctcacg gaggatctct ccgtgactgc aggtcgcgca 74340
gtcgccgtgc acgtacttga ggaaggcggc gtacttctga cccgcgttca cgaaatttaa 74400
gcgcgcgtcc agagagggca gcaacagatc gtagacgcgc ggcagcatcg gctcgaactg 74460
taatagcaga tcgtcgtcaa gatcgggtag cgcgtgtccg tcttcaccgt cctcgtcgtc 74520
accacctccc ccctcgagcc caccgctcgt accagccgcg ggctccgcgt cctcgtcgat 74580
caccagcggt cgcgtcggca ccggagaatc cacgtcatcc tgcacgtcgt tttcctcctc 74640
tccgtcgtca tcgtccagaa acggcacccg ctgcttagcc caggattccg gttttagaag 74700
ctccacatcg aagacgagag tggcatgtgg tgggatgatg cctgggtgcc cagtggcacc 74760
ataggcataa tctggagata tagtcagttt ggctctctga cccacactca tctgggcaac 74820
cccttcttcc cagcctcgga tcacctcctg cttgcctagc ataaacttaa agggcttgtt 74880
tctgtcccgg gaggaatcga ctttctttcc atcttcaagc atcccggtgt agtgcaccac 74940
acaggtctgg ccgcgcttgg ggaaggtgcg cccgtctcct ggggagatgg tttccacctg 75000
cactcccatt cttttttccg cgtcctcaat cagcggcgcc gatcgccatg aatccgagta 75060
cccacgtgag cagtaacggc ccaacgactc cccctcacgg gccccacacc acgtttcttc 75120
ccccgaccag cccggccccg tccaccagct ccgtcgccgc cgctaccttg tgcagtccgc 75180
aacgacaggc cgtttcgcgt tacagcggct ggagcaccga gtacacccag tggcactcgg 75240
acttgacaac tgagctgcta tggcacgcgc acccgcgtca agtacctatg gacgaagcgc 75300
tggccgccgc ggcggccgcc tcataccagg taaatcctca acaccccgcc aaccgttacc 75360
gtcattacga attccagacg ctcagcctcg gcacctcgga ggtagacgaa ctgctcaact 75420
gttgtgcgga agaaaccacg tgcggcggca cgcaatccac cgtactcacc aatgcgacca 75480
acaccactag ctgcggcgga gccgtcgccg gcagtagcaa cgtaggaccc gccggcgctt 75540
cggccgcctg cgacctagat gcagaactgg ccggcctcga aacctcggcg gccgactttg 75600
aacaactgcg gcgactgtgc gcgccgctgg ccatcgacac gcgctgtaac ctatgcgcca 75660
tcatcagcat ctgcctcaaa caggactgcg accagagctg gctcctcgag tacagcttgc 75720
tgtgcttcaa atgcagttac gcgccccgtg cggcgctcag cacgctcatc atcatgtccg 75780
agtttacgca tctgctgcag cagcactttt ccgatctgcg catcgacgac ctgttccgac 75840
accacgttct cacggtcttc gatttccacc tgcacttttt catcaatcgt tgctttgaaa 75900
aacaagtggg cgacgcggtt gataacgaga atgtcaccct gaaccatctg gccgtggtgc 75960
gggccatggt catgggtgaa gacacggtgc cttacaacaa gcctcggcgc cacccgcaac 76020
agaagcaaaa aaacaaccct tatcacgtcg aagtgccgca agaactgatc gacaactttc 76080
tagaacacag ctcacctagc cgcgaccgct tcgtgcagct gcttttctat atgtgggccg 76140
gcaccggcgt catgagcacc acgccactca cggaactcac gcacactaag ttcgcgcgac 76200
tagacgcgtt atccacggcc tcggaaagag aagacgcaag gatgatgata gaagaagagg 76260
aggatgaaga aggaggagaa aaaggaggag acgatccggg ccgtcacaac ggcggtggca 76320
ccagcggggg gttcagcgag agcacgctaa aaaaaaacgt gggtcccatt tacctatgtc 76380
ccgtacccgc tttttttacc aagaaccaaa ccagtaccgt gtgtctgctg tgcgaactca 76440
tggcctgctc ctattacgat aacgtcgtcc tgcgcgagct gtaccgccgc gtcgtctcgt 76500
attgtcagaa caatgtgaag atggtggacc gcattcagct ggtattggcc gatctgttgc 76560
gcgaatgcac gtcgccgctc ggcgcggcac acgaggacgt ggcgcgctgt ggactcgaag 76620
cacccacctc gcccggaggc gactcggact accacggcct gagcggcgtc gacggcgcac 76680
tggcgcgacc cgacccggta ttttgccacg tcctgcgtca ggcaggcgtc acgggcatct 76740
acaagcactt tttctgcgac ccgcagtgcg ccggcaacat ccgcgtcacc aacgaggccg 76800
tgctcttcgg acgcctgcac ccccaccacg tccaggaggt gaaactggcc atctgtcacg 76860
acaattacta tataagtcga cttccgcgac gtgtgtggct ctgcatcaca ctcttcaagg 76920
cctttcagat tacaaaacgc acctacaaag gcaaagtgca cctggcggac tttatgcgcg 76980
atttcacgca gctgttggag agttgcgaca tcaagctggt ggaccccacg tacgtgatag 77040
acaagtatgt ctagcgtgag cggcgtgcgc acgccgcgcg aacgacgctc ggccttgcgc 77100
tccctgctcc gcaagcgccg ccaacgcgag ctggccagca aagtggcgtc gacggtgaac 77160
ggcgctacgt cggccaacaa ccacggcgaa ccgccgtcgc cggccgacgc gcgcccgcgc 77220
ctcacgctgc acgacctgca cgacatcttc cgcgagcacc ccgaactgga gctcaagtac 77280
cttaacatga tgaagatggc catcacgggc aaagagtcca tctgcttacc cttcaatttc 77340
cactcgcacc ggcagcacac ctgcctcgac atctcgccgt acggcaacga gcaggtctcg 77400
cgcatcgcct gcacctcgtg cgaggacaac cgcatcctgc ccaccgcctc cgacgccatg 77460
gtggccttca tcaatcagac gtccaacatc atgaaaaata gaaactttta ttacgggttc 77520
tgtaagagca gcgagctact caagctctcc accaaccagc cgcccatctt ccaaatttat 77580
tacctgctgc acgccgccaa ccacgacatc gtgcccttta tgcacgccga ggacggccgg 77640
ttgcacatgc acgtcatctt cgaaaacccc gacgtgcaca tcccctgcga ctgcatcacg 77700
cagatgctca cggcggcgcg cgaagactac agcgtcacgc tcaacatcgt gcgcgaccac 77760
gtcgttatca gcgtgctgtg tcacgccgtc tcggccagca gcgtcaagat cgacgtgact 77820
attttgcaac gcaagattga cgagatggac attcccaacg acgtgagcga gtcctttgag 77880
cgctacaaag agctcattca ggagctgtgt cagtccagcg gcaacaacct atacgaggag 77940
gccacgtcgt cctacgcgat acggtctccc ttaaccgcgt cgccgttgca cgtagtttcc 78000
accaacggct gcggcccctc ctcctcgtcc cagtccacgc cgcctcatct ccacccgccg 78060
tcgcaggcga cgcagcccca ccactactct caccaccagt ctcagtctca gcagcatcat 78120
caccgtcccc agtcaccacc gccgccgctg tttctcaaca gcattcgtgc gccttgacac 78180
tgtacggcag aaaagccggc tccaagtgca agcgccgcgg cagcaccatg tgcaaaaact 78240
tgtccttgcg cgcggtttcg ccgccgggaa agacgggcga cagcacgtta gttacagcct 78300
tgagaacctg ctcaaagtac ttgtcggcgt gaatgggcac gccgtgctcg cgcacgtagc 78360
tcggatcttc ggctacctcg tagttgcaca cggccgacgg tggtttccgc gccctcttct 78420
ttgccggctc tcctcctctc ctgttgctct cctctacccc gccgccgtca gcgtcgtcgt 78480
ccgtgccatc aatcgcgtcc gaccgggaaa ccacgccggc ggttacagaa tcaccgttgt 78540
cggaggaacc ctgcggcgcc gtccggacac cgggcgccgt cagaacgtaa aagacccgat 78600
ccccgaccga gggtagctcc tcagaacggg ccgccaatcg cttaatgacg gcaatgtgcg 78660
gcaggttaga ttgacggtac agcgagatgt ccttagagag caccgacgaa agcaccaggt 78720
cctcgacacg cacacggtgc aggtacagat cgtcgcgggc ctgcaccaag cggcgtaaga 78780
tacgccagaa accgcgtggc acgccgtact tcttgacttc atcgagtgag aggcgcgaca 78840
ggcgcacggc tgcttccgag acctcgcgat cctcaaagag cagcgagagg acgtcacgcg 78900
tgacgccctt gacgaactcg caggccgtct tgcgcaccag atccacgccc ttcatgctca 78960
gacccgaggc gccctccact ttgccgatgt aacgtttctt gcagatcatc ataagagaga 79020
cgaagacctt ttcaaactcc agcttgacgg gctccacaaa aagacaggcc gtcacgtagt 79080
gcgccaggct gggcccacgc gccaccagag cctgcggcgt caggccacga aagcggacaa 79140
acacgctgtc cgtgtccccg tagatgaccc gcgcctccac ccgccgttcg ttcgagcccc 79200
ctgacgatgt ttcgagcccc tccggtaacg cgctgctctc ctccgaatcc ccctcccgcg 79260
ttcccactac atagtcttcc tgattaaaaa aattgtgcaa aaaacacggc tctgaaaagt 79320
tgtctttgat gaaccgcgcc gtgcgctcta gcatgtcgcg accgatgcgc gtgatgctgg 79380
cggcgatggg cagacacggc atcataccgt tgaccacgcc ggtaaaaccg tagaaagcgt 79440
tgcacgttac tttgagcgcc atctgttcct tgtcgagcag catacggcgc acagggtctt 79500
gacactcgcg catgcattcg cgcacggcac gccgctgcga aacccacttg ttgagcagtt 79560
ccgagagcac cgagacgcgc accgaagcac gcacaaagcg gtgggtcacg ccgttctcta 79620
gcgtgacgct gtatacgtcg gcggggtcca cagggtactc gccacccggc accagcaggg 79680
tggagtagca gaggttgtgg gccatgatga tggaagggta gaggctggca aagtcgaaca 79740
cggccacggg gtcgttgtag taacccacct cgggctcaaa caccgtggcg ccctggtacg 79800
aaaccgccgc agtaccgccg gcgccgtgat tgtcgttgga aacgccgacg ccgccactac 79860
tgccggagcc gacgctgaaa acgccgacgc tgctactact gttactgccg gagccgggtg 79920
aaacgccgtc ctgactggac ggcgcagatt gcaagggcgg cgacatctga aacatagccg 79980
ccacagaacc cgcgtcgccg ggcacagcgg cggtagagat gatagcagcg ttaggtgaca 80040
cagcaacgct attcgtttcg ggcaccgtcg tacctttgct gtagtggttg ggcaggataa 80100
aatcgcggca ggcgcactcg tccagcagcg aggtgtagat acggatctgc tgtccgtcaa 80160
agatgacacg ccgcaacgga attttagcca gccgcgcgat ggccccggcc tcgtagtgaa 80220
aattaatggt gttgaacaga tcgcgcacca atacggcgtc ctgcagacag taacggccta 80280
cctgggcgcg gccctcggca ttagccacga aacaacgcgg gatgtccttg taagacaggt 80340
catccttgcg ttgccgcagg taaagctcgg ccatagtgtt gagcttatag ttgggcgagt 80400
tagtcttggc catgcataca gggtacatgt cgataaccac cgaacccgca atatacacct 80460
tggtggcggc cgtgctggcc ggattgttgt gagaagccga gggaaaagcg gcggcgtact 80520
gccgcttaaa acccacggcg gggctgtgta aaaagaaacg gccgccctgc gccgtaggca 80580
acttgcagaa gcgctgcgag tccaccttat acaggtactc gagacgcgtg aggatgtact 80640
tcaagtcaaa agagttgatg ttgtaaccgg tcacaaaggc cggcgcgtac cgttgaaaga 80700
aaagcataaa gcccagcagc agctcgtatt cggaagggaa ctcgtagacg tccacgtctg 80760
ggcccacctg cccgcaggtg ccgatcgtaa agagatgaag acccgagtgc ccaaagatca 80820
caccctccga agtgcagccc cgaccatcgt tcccgtttgg gatcccctga tccacggcgg 80880
tgtttccccc cgtctcgtag cacacgcacg agatctgaat gacaatgtca tcggacttct 80940
cggcgcaggg aaaaccaccc tcgccgctca tgcactcgat atcgaaggac aggcatcgat 81000
agcgcggcca cgagctgtcg tcgggcacag ccaccaggtc agagacatcg cagtctacct 81060
cgatatcaca agtcgacgcg cgaccctgct gccgccagtc gtaacgattc acggagcacc 81120
agccgaacgt ggtgatccgc cgatcgatga ccaaacgcgt cagcggatcc acacggacct 81180
cgtacacggg aaaaccctgc tccagcagat actcgccgat ttttctggcc atggtccagt 81240
tgctgataga cacacactgc aaatcgggca cgggtcgcgt cccgtaccca tagatggagg 81300
tcttggtggc cggcgtgaca gacacggcgt atggcgtccg cggttcgggc actagttcgc 81360
ccacgctggc aatgacctca cgcagcctat cggtgtcgct gtactcacag taaaagtagc 81420
tgcgctgccc gaaaacgttg acgcagatac tgtagccgtg ttctgtggcc ccgaagaaac 81480
gcaacacgtt ccccgaaggc accagatgct gacgatagcg cggcgacacg ttttcgggcg 81540
agtcgaagaa gagcacggcg tccgtctgat cgtaggtgtg aaaacgaata ggtcccacca 81600
cgcgacccac cagggtctcg cgccaaggac acggccaaac catgtcatga ctcaacaaat 81660
gtttaatctc tcgatagaac atgagaggca gccgtcccgt cttatgcttg atcaaccccg 81720
tctgaccgtc gaacatgaca cctcgcggca cgatctgcaa aaactgtttc tgtggcggcc 81780
gcttgcccga gccctgcgcg gagccgggct gcgaacgctg acgccggcca cccgcgaccg 81840
caccgccggt cacgccgccg ctcagatacg ggttgaaaaa catagcggac cgtgagaggc 81900
tgacagctta cgaagcaaaa tcacaaagaa aatacacatg cagcacctag atatccagtt 81960
taaccccgta tatcacaagt ctctgtgtca atattttttg tctagttttt ttttcctcct 82020
ggttcagacg ttctcttctt cgtcggagtc tttcaagtgt ctgtagccgt ttttgcgatg 82080
tcgcagccgg tctagcaggt taggcttctg tcccttgtcc tgcgtgccag tctgtccgtc 82140
caaagaatct gtaccgttct gctgcgctcg ctgctctgcg tccagacggg ccagggccag 82200
aagcatctgg taagcctgct cgttggtgta aggcggagcc gccgtggatg catcagacga 82260
cggtggtccc ggtcctttgc gaccagaatt ataaacactt tcctcgtagg aaggcggagc 82320
ctgtaacgac gtgtctttgg tgctgcccga cgtcacggtg gtcccgtcgg cggacaccag 82380
atagggaaag aggttctgca gcggctgcgt gcacagacgc cgctgtcgag tatagatcaa 82440
ataagtgata atgactacgg ctatggccac gaggatgatg gtgaaggctc cgaaggggtt 82500
tttgaggaag gtggcaacgc cttcgaccac ggaggccacc gcgccaccca cggccccaat 82560
ggctacgcca acggcctttc ccgcggcgcc caggccgctc atgaggtcgt ccagaccctt 82620
gaggtagggc ggtagcgggt cgactacctt gtcctccacg tactttaccc gctgcttgta 82680
cgagttgaat tcgcgcatga tctcttcgag gtcaaaaacg ttgctggaac gcagctcttt 82740
ctgcgagtaa agttccagta ccctgaagtc ggtattttcc agcgggtcga tatccagggc 82800
gatcatgctg tcgacggtgg agatactgct gaggtcaatc atgcgtttga agaggtagtc 82860
cacgtactcg taggccgagt tcccggcgat gaagatcttg aggctgggaa gctgacattc 82920
ctcagtgcgg tggttgccca acaggatttc gttgtcctcg cccagttgac cgtactgcac 82980
gtacgagctg ttggcgaaat taaagatgac cacgggtcgt gagtagcagc gtcctggcga 83040
ttccttcacg ttcatatcac gcagcacctt gacgctggtt tggttgatgg tcacgcagct 83100
ggccaggccc aagacatcac ccatgaaacg cgcggcaatc ggtttgttgt aaatggccga 83160
gagaatggct gacgggttga tcttgctgag ttccttgaag acctctaggg tgcgccgttg 83220
atccacacac caggcttctg cgatttgcgc cagcgcccgg ttgatgtaac cgcgcaacgt 83280
gtcataggtg aactgcagct gggcgtagac cagattgtgc accgattcca tgctggacaa 83340
atgagttgta ttattgtcac tcgtacttct tctggtccta tgagtgatat tcagactgga 83400
tcgattggcc aaacgttcca attccaccaa agatttttgc ttgatgcctt gccagaacac 83460
caccagaccg ccgctggttt cgaagacgga cacgtttccg tatttttcat atgtttgatt 83520
gtatgaagta ttgaaaatct gctgtaactt atttatagcc tcatcacgta cgcagtccag 83580
cgcggagtcg gacatgttca cttcttgttt cttagacaga aaagttgcag tcattttggc 83640
agaagaaaag tggtacgagt cttcggcttc ggaacggata gtacgttccg aggcttccca 83700
gaaggtgagc tggcaggtga cattcttctc gtcctgtata tcccaagaga tcaccgagtc 83760
ggcacgttcg agaaaagcca ccaacctatg ggtttctggc gcagcgttgg gtcttccaaa 83820
gtcggaaacg atggtgtagt tcgggaaaat gaaaaacttg tcggcgtttt ctccaaagta 83880
gctggcattg cgattggttc cgttgtagaa aggagaaatg taaaccacat cacccgtgga 83940
agttgcaaaa aaatgataag gatacttgga gcgcgcagta gtgatggtca gcatacagtt 84000
cagattacag gtctcacgat agagccaggt gctgccgcgg ctgtgccact gatccttgac 84060
cgtcacgtaa cgggtactgt gggtgttgga ataatcgtcg ggaattaatt gcatggtttt 84120
gttttcataa ctgtccctat gatatgccac gaaaaccgtg cctcctataa cgcggctgta 84180
ggaactgtag cattgagcaa acttgttgat gtgatgaatc tcccacatag gaggcgccac 84240
gtattccgta ttgctgccca gcagataagt ggtgtagatg taagcgtagc tacgacgaaa 84300
cgtcaaaacc ttttggtaga cccgtacctt aaaggtgtgc gccacgatgt tgcgcttgta 84360
gaccaccatg atgccctcat ccaagtcttc attgataggc ttcatcgagg tgcagatgat 84420
attacgttca aagcgaataa gatccgtacc ctgggccata gaacacacgc gataggggta 84480
cttggtagtg ttgactccca ccacatctcc gtacttgagg gtagtgttgt agatagtctc 84540
gttggctcta tgactgacgg cttcagaaga cgttacgtgt tgagaataga ctgaccgggt 84600
ttgagcagac gtcgtacgag aagtatggct tccattgtga gtagaagaag ttgcatggga 84660
agtactagaa gaggaaaccg cagcacccag acagacgata cacaggttaa cgcagactac 84720
caggcaccag atcctggatt ccatgttcgt cgcgggccaa atccagcagc gatgaggcgc 84780
gtcgtggtct cttgcgtgtc gcgcggaccc tccgggaaac acccgcagtc gaggaggagg 84840
gatacggact tggcagccaa ggtcggtccg gctccctgaa gacacccgag acggccgcgg 84900
cggccgtcag ggtggagggc ttggccacgg gagctgttgg cacgtcgcca ctctcatccg 84960
gtctggacag atgcctgtag aggaggagat atagatcttt ggacttataa agacttcctt 85020
cgtgacgaag cagcagcggc cactctttgt tatacgtgag aatcacatct ctgtccgggt 85080
gcagttcgtc gcgcaggcac gcgatcgaga gttgtttccc gaaagtttca ttatatagtg 85140
cgacggagag cacgagctcc cgcacgtgca tccacatctc cttctgcagc acgtttaggt 85200
cctgacagtc cgaaaaattg aaaaaaccca tatacttcac caccatccac tcactgggat 85260
acacggtacc ttccgcgcat ttgaccaaat cgtccttgac gtggggtagt acgcccgcgt 85320
tgtcgcaggc ataggccatg tccacattgt gagagagggg ataacgatcg gtgcagtggg 85380
tgaagagggg cccgttacac aactcgtaga tctgctgacc cagtagcggg agggattcca 85440
caggcagact cttgtggatc aggttattga ccacatacag gtgctcatcg taggtgaact 85500
gatcacccac gtccaccacg tcttggtcct ggtggtattg gctgcggtac agaaacccat 85560
tcatgagctt agagataaag tccagacaca agggccccac tagattgaca tcgatgagct 85620
tgctagtcag acgctcctgc gttttgatgc aacggatcac cttgccatag cccacctccg 85680
agaccttctg caggtaggcg cgtttgcgca cgttcacctc gcgagtgacg ttgtggatgc 85740
gggagcgcgc gtccaccaag tcgagagcct cgtgttcgtc gcagttgcgc acccgtaagc 85800
cgttctcgct gccgtcgccg tcctgcccat tcacccctcc ccctaccact ttcttgcctc 85860
ctccacgagc ccggccgccg ccaccgttat tcctctgact gtgagtactg ctgttgctgc 85920
tgttgctggc cgtcatcaaa gtcgtacccg tccccgacat cgcctcccgt ccacgcaggt 85980
gaatagcctc gccctcgggg ccgtcgcccc ccgtgccatc tggcagcgga cgtcgaatct 86040
cctcgagaat atgcttgatt ttggtgtaca tctcgttgct ttcgtggagc ttgttgaaca 86100
ccgggttgtc ctcgaaagct tgaatgctga gggatgtgat gaggtcgatg atcctgttgg 86160
gggcggcaaa gaccgacccc acgaacatgc gctcctcccc gtccaacgcc ttttccccga 86220
gcacgaagat gtcctccacg tcctccccgt acagatggcg actgatgccg ttcatgagcg 86280
cccggcacag ctggtgatac acatttagct gctggatggt gatgcccacc cgcttgacga 86340
taacctccga ggtacgggac cagtaggtaa aatccgacaa ggaatatatt cgttccggta 86400
tatccgtaaa caggttgtac tccctcagcg cctcctccgc ctcctggatg tagctgtggt 86460
aggccgatga agaagagaat aggcttttga gggccgaaag gactccagcc aagtggggga 86520
tgcgcgttgt caggtccagc aggtcctgct ccaccgtctg gatattcaca tcggactggc 86580
ttgacggacg gtggaccgct atatggttgc acagcaagcc ctgcagccgc ttgttcagcg 86640
agcggccctg attcgggatg atggtcagct cctcgtagca ttgggcgcat gtcgtccctt 86700
cgacgtacac ttcctgacgc gccaccggcg agatgccgca taggcgacgg aggagctcca 86760
gcaactgcgc gcagacctcc aggccggcct ccggcgccag gatcccgtac acgtagttca 86820
ttttgcacag gaagcgctcg atgtcgttga gtgtggccag actgacgctg aaacggacgt 86880
tgtccgtaaa ctggagctcc acggtgtgat ggcgatcgca gcgatccaaa cggaggacgg 86940
tacggtagaa ggccgcccgg tccggctggc gcgagtaggc catcagcgcc cgatccagca 87000
aagccgtatc ctcgtgcagc gccttcagca gcatctccag gtagagcgtc agcaacgaac 87060
tctgcgtacg attctgcgcc accacctccg ggtagatctt ccggtacaga tacactatag 87120
ccgccgcgtt tctcttgaac ggcgtggact ccgccagtaa cacgttcgga tcgcagtact 87180
ttagacactc cagctccatg gcgtattcgt tgcatttcga acacactacg catagtttct 87240
gtaacaaatt catctccatg actcgactcg ctcacgtacg agacgctgtc gtccggtctg 87300
gcgccggcca gagacatgga gtcggtgcac aaataactcg cgggccgctc gctatgccga 87360
ctgacgttga cgttaatata taacgacgtc gtcgacgacg cgggttctgc tcccgaagct 87420
gttgccgccg cttgcggcgc aacctcctcc accaccgccg ccgccggctc ctccgcctcg 87480
ggcgacgggg gctcggagat gaccggctgt gtctgacact cctccccttc ctcaggcggc 87540
ccgggcgccg acgcgaatgt cggagtttgc cagcgcggcg gcggtctctg tctctggtgc 87600
cgcggcgcta accttcgggg ctgttgctgc tgttgatgat gcgacgccgt ctgtcgccgc 87660
tgttgcggcg gtagctgata cggtgtcgcc tggtgctgct gtgtcggtgg ctgctgttgc 87720
tgctgttgtt gcggtctgaa aagcggccac gggggctgcg actgttgttg ctgttgttgc 87780
gatgctcgtg gctgcggcgg ccgttgtcgc ggcgtttgct ggcggttaca accggctgcg 87840
tttggccggc aataacccgc tgcccccgcc gcccccgctg ctcccgccga cgccgccagc 87900
ctcgtcttcg ccggcgttca cgagaaagca gccacctccc gtctcgccgg gcacgccgaa 87960
gcaaatggag ttgcccgcga cggactcgcc gagaagaaga ccgccacccc cgacgccgga 88020
cgccgcgccg acgccactgg gcgcgaagag cgccgacagg tcgtgcacct cccccccggc 88080
ggcgtccgtt aatcgctggg cgtcggcgtc cagcacgcgt cgcaagttct ccagcgaaaa 88140
gtcctccacg ccctgctcct gcaacgcggc aaacttgtcc atcagcgacg cggccagcgc 88200
ctcgcagcca tccacgaaga agagcacatc gtcggacgcg gggatctcct cgcgcacgct 88260
cagaatctcg tacacggcca tcacttcggg gtcgcaatcc aagttctcgg cgtccagcgc 88320
cagcatgacg cggtttttta taagatccgc gtcaaaaagc acgttctcgc ggcgcgagcg 88380
tttgatgagc acgtcggcca gacgcgtagc caagaggtag cgctggcgca tgaaacgata 88440
atcttggccg ctcatagagc tcacgttaag gctgcgttcc acaccgttgc ccgaaaagta 88500
gccgatctgc ccaaactgat agatctcctt gctgttgttg atacccgcat atttttccac 88560
gctcacgggc acggtcacca aggaacgatg ctcaaaaacg ctccgtacca acgattcacg 88620
cgccacagtg gcggccatgg gcgccggcac gcctgcggtc ttcaagccct tgacatgcaa 88680
cgcaaattcg gcgggcgacg agaaccgcgg actagcacct aacacgtgag gaaactgcgc 88740
gtggttctgc gtcgttaagc gcgtcgtcaa cccgtgcagc gagccgatgt agtctttgaa 88800
gccataatag cagaggaatt tgttatggaa acggctttcc acgtaactca gcacacagtc 88860
tggcgccaca tccagcagat cgtgctcctg atagtcagcc gtcacagcca ccagaaattt 88920
gacgaaagca ttgaactcgc ccatgtcacc tatgggcaca ttcttgggca acgcgttgga 88980
acagaccttc tgccaaaact gtaagcaggg gagaccacat tcaggaaaga gtcgctcgtg 89040
atgtcgatac agcagaaatc ccaagcagcc cttagccgga ttacgacgcg gaacgtgatc 89100
gcggcgaaaa aacacgctac ccgcgttgcc cttgcccgcg cggtagatgg gtcggttttt 89160
cacccgcacc atgatcaacg tgggtaccga cagccgcgag agcttgatct ccatgggcac 89220
cacggcgtac gtgccctgcg cgtacagcct aaagtccagc aggcggtcgt gatccgaatt 89280
cttggacgac ttgatctgct tggtgaagag aaagcccttg cgcgacgacg tggtggagaa 89340
cgcgccgtga atggattgaa aatgctgcgt catccatttg gataccaagt tggtggtcaa 89400
cggattgtcc acaatgtatg aggtagcggt aataagcgcc acgttctgga tcacgtaaaa 89460
gacggatctg aaataggcgt aggctagcag cggctggaag gccacggcgt agggattcag 89520
atccaggttg aaggcctgcg tggcgcccgc cacctcgtcg cggctgctct tgaggcgcac 89580
ctccgaaacg aaacccaggg cctcgtcgtc cacaaacttg ttgagcgccg aaaagacggc 89640
cacaaagtcg cttttgccgt gcgcgctaaa ggtatcctcg cccgtcacgg ggtcgatgag 89700
ccgcatcttg cggcagtaat ccaagatgcg attgagccga taggtacggt ccacgctagc 89760
gcccaacatg cgaccgccgc gccccatcat tcccccggaa tccccaccac ccccaccacc 89820
acgaccgcca cccagaccgt cgctcgggcc cccgctcacg tctcgtccac cacccccgcc 89880
agcaccgccg cccggaaccc cgtcgtcacc tttgccgtcc aaacccccgt ccttggcgtc 89940
gacgttgtaa cgccgaccga agctgcccaa aatatccacg tcgttgagaa aacgcgactg 90000
cacggtgatc acgcagggct ccttcttggg ctgcttgggc accacgggca agcgggtgcg 90060
cacccgcacg aaggccgtct gataacacgt gtggcaacaa gtacccccac aggcctcgca 90120
cagccccgcg gcgcagccca ccaggtgatt cgtgagcgtc gacgaacccg acaagcccgt 90180
gttgtacacc gagacacgat tcagatacca gacgaagccc gaaactagct gcggacacgt 90240
gccacacacc aacgccaaat gctgcggccc atagcgttcg tccttgagcg gcgcgccctg 90300
aaacttgagc accttgcgcg cgtcgttgta gacgtcttcg caggccgccg acaacccgtt 90360
ggtgaactga atagccttga gcaacgtctc ctgactggcc gtaccgccgg cgctgggatg 90420
ccgcgccgac gactggagat acaccagcct gtgctggtag agcaccgaat tagcgctgaa 90480
gaccaaggcg gccacgtgcg tcgagagatg caacttgagc tcggtcagcg cgcggatcag 90540
atcgcggtga tcggttgcgt tggtcactaa aggccactcg gaaaagagca tagattcggc 90600
aggttggtaa gccgaatcga aaaataccga ggcaaaactg aaggccaact cgcaaaccac 90660
cgcgtcactc agcatcagat gatccttttc cagactgctg agtcgctggc tcatgtaccc 90720
caagtagcgc ttatgtggcg ccagcttcac cgactgctga ctgtcgtgca caaactgccg 90780
caacgccgcc tcgatcagca cacgcggctc cgagaagcgc agcgattgac accatgacgt 90840
gtacacgtag tagaaaagcg tctcgcttac ggccggcacg tagagccctc gcgcctccac 90900
aaaagcgctg cgcgcatcca gcgagacctc gtcggcttcg gcgtcaagct gcaacgaatt 90960
aaagagcgta ggcgggtaca acggcacgcg caccgcctcg ccgccgtgca gtcgcaccgt 91020
ggtcgcctcc tccacgcatg gaatcagctg accggcaaag agaaactcct tcaagccgtt 91080
gcccaccacc acgtgcacag tcgtctcgga cgcctgacag cccaccgccg cgcacaacgc 91140
cgccagatcg gtaggcacgc gatccgcctc gggcatgtaa gcctccaacg cgtacttctg 91200
gcgggcgtcc tcgcacagcc gatgcacgtc tccgtgatcc tcggtaaaag ccacgatgcc 91260
ttgcgtatga tgaaagtaga gcgcaaaagg acagaaggac gtgactttcg tgagcacccc 91320
gccgtcgtaa caaagcacag gcgtgcgcac agagacgccg aaatccgcct ccaccgtgag 91380
ccccgccaac aaaggagcga tcaccacgct cgaggaacgg tcgcatagcg agagagtggc 91440
cagaatctcc tgcgtttctg cgttcaacct gctgaagtag agaaaagccg cgggccccac 91500
cggcgctagc gcggttagtt cctcgtggct catggtggat gaacggaaga caatggctac 91560
gccgccactg agtgaatttt ataccaagga aaagttcagc acgtcatgtt tgacgcacga 91620
cgtctgagac accaccgtgg ccaccactgc ggtctggctg cggttgcgga ccaccaaagg 91680
cgacaaccgc aacgatccca gcaattcgta agaaaagcta accgctacgg tcaggtagcc 91740
tctcgcagcc agaccgctag ccgacgcacc cgcccgcgaa aatagcgtga tgttcgggac 91800
ggctttgcgt caccgccaac taacgtcggt agtcgagcac gtcgtttatc ctcagcacac 91860
cgtccgatca caatccgttt tcccactcag tcgcacaagc agcacataaa aaccccacac 91920
agggcacgtg aaaacaccgt ccctagaaaa cggcgttttc tgtcctaccg tcacccgtat 91980
acacaggcaa atcccaatcc cgatccccga aaacaccgta cggtgtttgt gacctccaaa 92040
atcacatcag ctaacaaacc gtgaaaagtc acgtttcacg aacacggtgt ttttaaatca 92100
caaagaaccg cctgacggtt tacaagcaga aacaccgcac cacggtggta caagcgcgat 92160
gaatctggtc tcgcaacctc aatcgccgct atcaccaccg attttcgctg cgctccgccg 92220
acaaaacgcc gtacaagcta cacaccccaa aaacccgcgc gcctacgggc gccaaacctg 92280
tgtgttatct caacgtcaca acacgacaca aaccgcgtaa cgtggtttcc cgaacacgta 92340
cgcggcacag acccccgaca cgtactcgaa gaccttacag tttacgagtc aataaaacag 92400
gaaaagatcc gaactttaaa attgtgtgtt tttattttcc catccccctc tttttaccaa 92460
aaaacacatt tttcgtcttg taaaaagtaa ctttcgccca ttgccatgaa acaccgtgat 92520
ggggaacggt gttgtgtgtc gactgacgtc actacggcga tcagtatcga cgtcgtgtat 92580
acataacggt gcccggtgtt tttattcggg gcgttgtcgc gtcttgatgt aatgtaacct 92640
gaaaccgccg tgcccaagaa tgcggaagcc agcgtgtaat cataacgggg ttttgggtac 92700
aatctgacga catctggcgg cgagcgtaca ccatcgaatg tggcgatcgc cggctctacg 92760
tcacaatgac gcaaaaacac actgtaaaac ccgcgtagac agctttcctg gtcaacgagc 92820
gccatctggt gtcggcataa gaacaggcat caaccccgtg gccggcgagg cggtgagcac 92880
ttttgttggt cacgtgacca tcagcgcagg aagcgaggcc cgtagaaccg cccaagaggc 92940
ggtgccagat gccaacgtca taatcacaag gtgatttgtt acgtcacgcg cgcgcacgca 93000
cgcgcgcggt agaatacagc gatccctagt gaagccacac ccattacgtg tagccatatc 93060
cgcttacgta tacagccaca cccctaggta cgccacctta tctaccaatc acagaaacgg 93120
atatacaatg acccctccct agactccacc ccttgtacgg aaatttcaga taggtggaac 93180
ccgttagggt tccaccgtcc tcggtgtacg tacaggcttc tccgtctacc ggaaatatac 93240
acctgctgac gtagacgcta ctcccggata cgcgtcataa gctactggac cctagggggg 93300
agtgtctaca gggctacgtg cacgccccct tacctagggt atccgccccc ttcctctgtt 93360
ttggcctagt aaacttaacg ccgccgcttc tcacgtgacc cctgacaagc ctacgtcaca 93420
ctcgcgtgac cacacccact ccggatatac gtcatcctgt ggaattccgg acatacggtg 93480
acgtagcgag cgtagcgagc tacgtcacgt atgcgtgcgt catctccggc ggaaatcatc 93540
tctgatgacg tagcgagcga agcgagctac gtcatcagtc cgttttacgt ataccggatg 93600
ctaggcgacg ccccgtaggg gcggagccta gcttccaccc ctaggatgca taccctatat 93660
agcataattc ttctaacgaa acgttctacg aaaacggact ggcggaacgg gaaccaccgt 93720
aacccccccc cctcaccccc ccccttctcc tccggaaccg gggggggcaa atttttacca 93780
aatttgggca accatgattt ccaatgggac ggcgtttccg tgcgcatgcg cagtcggggc 93840
gagtttttgg ttgtcagggc gttgccacgc ggattatggg atggtgactc gagtgcgcat 93900
gcgccgggga tgccgcatgg aaaacctata tataaggagg ggtgaaccag gggccccggg 93960
gcgcatgcgc gggccagggc ccgcgggagg gtcgccctgc gcatgcgccg gtaaaattcc 94020
actgtgtgtg tcgtgcgcat gcgccagtat ttttccacta gaggcggtca gtgcgcatgc 94080
gtcggtaaaa ttccactaga tgtgcgccgt gcgcatgcgc cggtattttt ccactgggcg 94140
gccgcaccta gggagcgcga gccccgtgcc gggcatgggc cgcggcggtg gaaaattacc 94200
gctccgccca cctaggcggg gcatctgaaa acctataaaa cccggcgtgc ccgccgcccc 94260
ccggcgcagt ccgcggcagg gttccggccg tgctgcggtc cgcacgctgc gcccgctccc 94320
gcctgcctcc cgccctaccc cccaccctcc ccggccgagg cccggcgccg gtccgtccgc 94380
gggcccgtcc caccgccctg gagcaccatc cggggccgtg ggccgggcac cgggcgcggc 94440
ccgctccgga cctcggccgg gggtccctcc cctccccccg ctcgaccccc ccatccgacg 94500
gcccggccgg gctgggaccc ccgcaccggg gtcccggttc ccgtccgtgg cccgggggga 94560
cccgagcggg ggcttcccac ccccaccccg ctcctccccg ggctccggcc cgggatccct 94620
cgctgctccc ggcgacctcc gccggcttcc cggtccaccc gccgcggaat ggacgggacc 94680
cggggtccgc gcccttcccc tccccccacg gggggctggg tcgcggaccc cggttcctag 94740
gctcgttccg cggtgggcga ccggggatcc cccacccagc tccccttccc ggcccgcctt 94800
gctggctttt gggcccctgc gggctttttt tttccggctg ggggtcgcgg cggtcggccg 94860
acgacgacgg taggtgggcc gggtggacgg tggtggggac gggcgacgcc ccggctcgac 94920
ggcaatcggt cccggaaggt tgggggctgg gggcccggtc aggagctccg ggagcggggt 94980
cgaccgcgac ggcttccggg tctcgcggcg gctccctctc ggcggctccg gttgggctcc 95040
cctcccccct ctcgagggtc cggccgccag tcgtgaccgg gggtccctcg gcctagccgc 95100
cggctctcgg tccgccttat cctgggcgtt ggcctgtccc gtgacgctcc cctcccccgc 95160
tgctccccaa aaaaactccg cccgaaccgt cgcggcttgc tggccctggg cgtggtcccc 95220
cactcccctc cccccatcgg ccgcccagcc ggggtcggcg cctcggaccc caccaggctg 95280
tggcgtgtgt gctggccgat gcggcggcga ggttgggtgt ggccggaagc gctcggggtc 95340
gacggtgggc cgccatgaca cctcaattgt cgtcagtacg cccctccaca atcaccgtcc 95400
ccacacgatg ggcccggcag gtcacccaac gttggttcag gcccagtcgg gttttttccc 95460
cggcacgaac gcacgtcccc gtgggctcca cgcgttttcc accctttcct ggaggggtcc 95520
ggaacaccgt gaatccacgg ggagggtccc ggcacgggcc gaggagacca cgaccgtccc 95580
acccggcgtg tcgactcgtc cgagacccgg gaagggaaca ggccccacct ttttttccct 95640
tctccgattt tgccgtggaa aacccgtgaa ccgatacggg tgcagacggc cgaaaaaaat 95700
cgagacgaca atatgacggc agggcgcgat cttctccccc atccgacaaa accgtgtccc 95760
ttaaaattcc ccacctttct ctgttcaaat ggccccgaaa ctgtaaaaca ccgtttgacc 95820
gcaccccaac cggcgccatc ttggtgacct tctcgacggt tctctcgctc gtcatgccgt 95880
tctgagctcc gacatggcgg acgagagaaa atggcgtcga gagcctagga gcgtttttgc 95940
tccaggcggg taaaaaaata gcacgataac ttttctgtgc ttttttttga gacgttttag 96000
aagagctttt ttctgctcag agcgaaaaaa tgatagccct gaaaatctcg acgagtctgg 96060
ccgagcggcg ccatcttgga ggaggggcga gtcgcgggca ccgcctcggt accccctggc 96120
cgaggcgagt ccgcggtcgc cgcctgttcc gtgatgctac ctagagggcg ctgtcgaggc 96180
gactcttcct gttttcgccc tgagggctaa cggtcgctga cgtcaaacca tctcgtgctc 96240
gctgagtcac atccggttgt tgacaagcga tggaggaccg cacccaaagt gcgccctcta 96300
gtcatcgcgc ctgacccctt ttataaactg ctcgaagaaa agaacacctt atgtgaaaaa 96360
atacagaatg atgacaagtt catccaacac aaccgctcaa caacgccata tctatcagtg 96420
tccaaaaact atcttctatc ctttgaaact ataaatgctg cctatataca tatttagtat 96480
ccaagactct taccacgtag acgaaaagaa gtgatacaat gatcttgacg tgtatcgtct 96540
atatcgtgct agatatattc agataagacg cgcaaaccat agatttctca tcagtatcat 96600
gaaagaccta tagctctata tacgaaccta gtcattttag gacagccgcc ggagaagccg 96660
acgagggatc gggcgggtgc agccagaacc tcacgcccga tcccgcctcc ggtaggcgat 96720
ttgcatctgt ttggtaaaaa gctcataagt ctgtatgtga cctatatata ttatacgcta 96780
tgtacaccga actgtcgctg ttgtataaga agaaaaaact ctccatattt atatcgtctg 96840
aatttttgct tgatagacac gtgtttggaa ctctgtcccc ccacgttttc actgtgtata 96900
acaaaaatat gtgtttctca aaagatcttg aggtgtttga aaacggggga aacctgcgtt 96960
tgggtgctct aagccccgga ctgggacgta gccggcgtcc ggcacctata tttttctatt 97020
tttttttaca aaatatatga tgaaccaaga ataaaactct agctctcgtc tatttttaat 97080
atgctctact tagaaccttt ttaatgacag aatgaactcc atgttatacg ctctttatat 97140
agtttctctg cactaacctt taaaaccgta tccttccctg ttgtacaaat catcttttga 97200
tacacaatga tgacctgata tccctccata tatatgatcg gatattattc cgttagactt 97260
gtcctccttt tttttcctca tctcctgtat ctggagatat atgttgacca ccaccgccat 97320
gaccaccaaa aagctagccg tcacgactag aaatgtgtag gattcggact ttccgttcga 97380
gaagaaaaag agaccgcgtc tctggacgct ctttttgtca gtctgaatcg acccgggata 97440
cgtaagagag cggccctaca tcggggggcg ctcgagaccg acgacgttcc atctgaccag 97500
aaaaaaaaag gcacccctcg gtggcgacct ctcaccatcg tttgcccgtc cgcccgtcct 97560
tcgtagccat catcatctca ggctctatcg gtaccatcgt tgtcatctga aaaaaaaact 97620
gcctcaccca cctgcgtaaa aacaccatct ttccggaggt gcggtaagac gggcaaatac 97680
ggtcgtgccg aggcaaaaaa aacgcaccat cgacaccaca ccctcatgag caccacctgt 97740
cggtgttggt cgtcctccat cgttctctac gaacatctcg acgcccgggt gacggacgac 97800
ggcaagacgt cccggagaag acggtgttct ctcgggcggt acgctctctg gatctataat 97860
atctatagta gctaaacgag actgtgagta cgacgaacca catcatcttt tttttatgtt 97920
gcttctttag aaaatgactt atgtcgacga cactcggcat cagccatctc gtgaaacacg 97980
ctcgcttttc gtctctccaa ggaacactgg gtccgctgaa agggaccgtg taccgaccaa 98040
agcaaaaaac acacacgtag taacatgatc aaccacgtct gaatgacacg aaaacacaat 98100
cgtataacgc tctattcatg gaacgaactt ggaataaaaa aaccatcgca ggccagaggc 98160
taagccgaaa ccgtccgggg aagcgggcgc gagttttccg acttagcctt tggtgctcgt 98220
tgagcctctt ttttttttct gattctctga agaatcaccg tcacagccct atgacgcgaa 98280
atcaattgct agaacataaa cgttctcaac aggtatgaaa tgaacaaact agatgatgct 98340
ataaccttat attgtgtgta tatagatagg tgtgaaattt gtaggataaa aagtgtcgtt 98400
gtatgatgca caacgatcgt gaaactggag actgtagctc tctaccgaat gcaaatacac 98460
aaatgacatc gattcccgtc cccacataaa gaaatgtgct ttactgtgaa agaatgaaga 98520
agattcttgt tcctcgtacg acggggccct cgctcgtcgt gcctcttccc ccctccggga 98580
gaggggacgt cggggccctc cgtcgcaccg ggccgaagcc agtgaaatgt ttactacact 98640
gtcatcagaa tatatgatgt atattatttc ctccaaactc ctcaccatag ccaccaattc 98700
gcatcactta agaaagtagt agcaaccgcg gcggcggcga ccggccggtc gtcgtctcct 98760
cgtcctcaaa tgttgtacat gtgcagaaaa atgtgtaaat acgtgttatt tatcccatgc 98820
gtcttgtaca tagatatatg tttttatata cgctatttat actttatata tccttttgca 98880
taaccataga cagtcaagga ttttaatgat ttgctcatcc gcctttgagc catcgcttag 98940
gagttagttc ctctatgttc tcggcccacc ttttcgacta cagtagcaaa cccttgtact 99000
accaccccga taaaaaccac atcatcatcg tcaccacgac ctggaaacga cacacgttcc 99060
cccccaatct tgggcatgtg tatatataaa aagaatggga gggagaggac gtggggctcg 99120
agaagaaata aacgccaagc tcgattcgaa ccaaaaaacc acatgtgtat tgtgctttgt 99180
tttttttttt acggtggggg aaaaggaggg ggccgtcatt aacggaaacc gtgtatgggg 99240
tccggacacg aacagtacac agcttatggg gaaaaaagct cacagagaga aaaaacacca 99300
agctcaggca cgcgtacatc attattatca tcatcggata tctcaccacg ggtcatagta 99360
gtaccaagga gtgtgtaaca ccattttttc ttttctttgt aacgggataa gggacagcaa 99420
tcatcacgca caacaccctt cactctcttt ttagtcatcc atatcatcgc tgtaacacag 99480
catgtcctcg taatcgggcg tctggcagcg cattaccacc gagtcgtctt cttgcggtac 99540
cggtggtggt ggtggtggcg gcggcggctg ctgctgctgg gttgccgtcg tactgtgatt 99600
accgttggcg gactgcaccg ggatgatggg ctgcttgtgg ggaacctggg gtggactgcc 99660
gccgtgagaa ggcgacggcg tcatcaagtt aagctcacca cggtgactcc ggacaccggc 99720
gaggggcgcc gggggactgg gagggaccgc ggtcgtcttg tagacgacgg tgtccccgtg 99780
tcgatccgtg gctcgtacca gatcttgact gctagcgtcg tcactgtctt cgtcctcttc 99840
cagctcgccc tcagagtagt gctgctgtgg ttgcgacggt ggctgggcgg gaggagcggc 99900
ggcgatcatt ggagagggat gtcgatgact cccttctctg tcctttttat cgtaggctgt 99960
cagcgttgct gggtccgtcc tgctttccat atttgcgtat tgctcatcgg tgggatgaat 100020
ttggtctcct ccccgctgtt gtccgccggc agtggcgtgg ttgctggcgg ttgtcgttgt 100080
cgtaccggca aagacggtga gatccaatag cgactgctcg tcgaagggac agtacgctat 100140
catgaaacga tagggtgcca acgcgcgttg gatgcgcagt tcgcacatct cgttctgaca 100200
ctcgtggcac tgcagggcgc ctaggatcag gtccgagaca gcgccgcagc ggtaggtacc 100260
catggcgttg ttagtatcga actggtcaaa aaattggggc gtaccggtga cttgcaacgc 100320
gcgacggcgt agcgagacgg ccacgcgcga gaaagagcac acataggcca tggcgcggtg 100380
catgggttgc gagaaggtct cgggcggacg cttctgcaga tcgcagacgt cgtcgcgtag 100440
ccaggcgctc atttgaccgg gcttcttgac tagccgtttg agcgtgctgc aatggtcgcc 100500
ccagccgtcc tggtggtcca ggatgcagcc caggtccagg ttgttgagtt tgttgaagag 100560
tagctgacgc atgccgccca ccgtctccag atagggatcg tgcgggttga cgggtagccc 100620
gtgcaggtgg tggtacttca tgtagctgag cgtttcgtcg atgatggcca gcaacgtgtg 100680
caagttggga gcgttgtaca cggcgaagat cttttccacc accagcttgc gcagcaacgg 100740
ttcctccagc caatcgaact gttgacgaat gtgcaacagg tagtcggtgt gcatgagctc 100800
gtcgtgtgac agcaggatgc gaccgcgcgg ctgatgatct tgcgggaagg cggtggggac 100860
cttgagatcg gcggggtagg gtgccagacg tagactctcg gccgtgtagc gctgaaggtc 100920
gtaaacgggc gaggtagaac tcggtgaggt acccgacgag gcggcgccgc gctgcagacg 100980
cgctcttttt ttcttttcga tcaaacggct gagttgctgt agttcgtcct cgtccatggc 101040
gtccagttcg tcgtcaataa gcgccagcat ctgttgttgt tgcggtccgg cggacgatcc 101100
gtgatgatta ttggctgagg aggggtgaga agaaccgaaa gtcgtaggac aactgggaac 101160
tcggcgacga agatgcgtcg aatcgccgcc gtgatggtgc ggttcgccgt catcgttgtc 101220
gtaagactta ccgtagtggg ggttaagggg caccgaggcg gacgcggcca cgcgtcgctt 101280
gaaagaggag gacgccctat gtccgccacg gaagcccgcg gtgcccatga tgatgtgtcc 101340
gccggtgccc ccgagtgcgt ggcgggagga gggtggaagg ggaggaggat agtggtccgg 101400
atcgccttcg gtatcatcgt ctttgctgta gcggggtcgt cgtgcgggga cgcagggtcg 101460
gtgatgatgc gaggcggcgc cgacggtatc ttccgcgaga tggtgttcgc tggcggctgc 101520
tccgttccgt gtcgacggcg aggttggact tcgctcgcgt cggaacttcc gtggcacggg 101580
ttcgtaatcc agacagaagc gccgtgcgcg acgggcgcgg cgttcgcgct cgctcaggga 101640
agataacgac ggagcgtcgt gacggccgcg tgagtgcagc tccatggccg ccgtcgctag 101700
gaaggtcacg ttcgggcacg ctgatgtata tatagatgag accgctgccg gggggcgggt 101760
caccggcgcc gtggaaagtg aggctcagac ggcggtcgcc ggcggcacgg gcgcgtcggg 101820
cggtctgatt ttgatggaaa tgtggacgtt tttggcgttg gagtgacact ttttggtgaa 101880
acagcggctc cagaggctgg cccagagcgc gtagctgtgc tcggtgcgca ggtcgatgaa 101940
cacctgcacg gtctcttgcg ggttgcggtg cgtgtagttg agacagcgaa aatcccgcgt 102000
gcgcgcgccg tcgcgccgct tgacggccac gcagcaggcg ccgtggggct gaaagaggag 102060
gacgtggggc gcggtaaact gctcgctgac gtgcggttcg tagtgttgcg tgaggtgctc 102120
gagcagcggc ggccacacgc gggtgacgac gagccgctgc aagtccgtgt cggaaatcgc 102180
agcggcagtg gcgccgtcgc caccgtacag gtgataggcg agcacctcgg tgagaccgcg 102240
gcgtcgataa cgcgtcacgt taagcgagcg cgtctcgata aagttggctt cggtcgaggg 102300
gcagattttg tcgcgtacgc tgagaatgac gcgtggcggc ggcgacaggg gcaacgcggg 102360
caggtcgtgc ggcgggtggt ggtgaagcag gttacgcaga tccagttggg cgcgcacaaa 102420
gcctagcggg tgttcgcggt aggcgtcggg cacgatgaac agcggcaaca gacggcgatg 102480
catgaaatag ccgtcgtctt ggtccatttt atacatgtag ggcagacgta cagagcgtcc 102540
atggtggtag atgcctgtgt ctaggctgct ctcgggatgc gagatggggt ccagcagcgt 102600
gtgcagttcg gcgtcgagac agacggcgtg attgagcacc tgcgccacgg cgcgtaaaac 102660
gctggggtgt acggcgacgg tgcaggcggg gaacggcgtg atgatgcgca gccccagttt 102720
gcccttgcag cggcagtaag ggggtgacgt gtcaacggag gacgttgttt tttggaaaac 102780
gccgttatcc gggacgttat ttttatcctc tttcccgtct tcgtcttcct ctgtgtcgcg 102840
ctcgtcccgg taatcgagat agtcgtcgtc atcgaaaggc gcgccggccg cgtccacggg 102900
cacgctgttg ggtgggcacg cgcttttgaa gaaatagacc gggtgccggt cggggtgcgt 102960
gtagccaaag aggctcgccc atacggtcat ccagacgcgt cgtagtccgc gacatagctc 103020
aaagacggtg tgtcgcgcca gaccggagac gccgtcgcgc agccgtaaat caaagtcggc 103080
cacaaaattg aagacgggca gacgttcgtt gaagacttcg tgtcgcgtgt agtagaactg 103140
tgtctcgggg ctggtgctgg ccacgtcgtc gtcgtgtagc cacacggtct cggtcagggc 103200
ctcgtccgag aaacggctgt cgggtacgtg acggagcagg tcacgcggaa agaggctgcg 103260
atgccaggtt tcggaggcca cggcgcagaa gacgtgctgg tcattgggca ggtgtacgcg 103320
gtagacgggc agcggtcgct ccagcagcgg tgccagcgcg ggctcgggta gcaggtagcg 103380
acgttgcgag taacgcgtta gcgtgccggt ggtgtaagtc tgggctgtgc gtagcgaggc 103440
gcatagacgt aacaagccgg acagggagcg ttccagcggg gagaagacag actcggaaag 103500
cgtgttgatg cgttcgagct ggcgcgccag ctgcgtggag gtgccgaaga agcccgccag 103560
gtgcgtgccg tcgatgcggc cgccgtagcc ggccagcccc aagccgtgcg ggctggtcgc 103620
cgagtggggg gattcgtcga gacgcagtag gtgcgtctcc acgtagtcgt gtagaaagtt 103680
gtcgagcgag aagtattttt gcatgacgtc cagcagctcg gtggaaagcc ggcggcccag 103740
aaaacccggt tcgcgcgtgc actgcgcttc gggcgccgcg tcagcgtcgt aagccaccac 103800
gcgccggtac tcgagcaacc gcgcgcgtgc cagcgccgtg cggtaggcca ggtagacgta 103860
gtgcacgcag accgtgtcgg gcagacgcgc acgttcgcgg aacgcgttga tctgcgtgtc 103920
cacctgctct agctcggtgt agtcgcggcg gttgcgcgcg acggcgtacg ccacgaaagc 103980
ggacacgcgc tgacggaagg gcgagcccag tagcagacgc gcgaactcgc ccatggaggc 104040
gtgcgtgggg atgatggtgc ccaggtcgcg cgtgcagaag ctgcgcacgt actcctccac 104100
ggtggagatg gtgctgtact ggccctcgaa taggtagtag gccatggtca gcagcacctg 104160
gccctcggtg tgcccgaaga cgctgatgaa ccacgagggc gaggtggggc agaggaagac 104220
ctggttgaga tgacgtagca cggccgcgtg gtgaaagtac accaggtgct tgaattcgcg 104280
cacctcgccg ccgtgttcgg gcgagagcac gggcgtgcgg aaaagatgcc ggtagagcgg 104340
ttgcgtctcg gcctcgtcca gactggcgat gagcgccgag agggggatgg gctggcgcgc 104400
ggccaggtag cgcgagagct gcagcgtttc gttgttcacg gcgaagacgg gcgccacccg 104460
ccgcgagtcc gagcactttt gcgtctgtag gcagaagtaa acacgtcgcg agacctggtg 104520
tttgaccagc agggggaaga cgcagtggtc cgtcggtgtc tgcgagagta cgttggcgac 104580
tatatgagca gaatcatact ctgttgcgaa cagaacgagc gtcatcgtcg cgccggcacg 104640
atgcagctgg cccagcgcct gtgcgagctg ctgatgtgcc gtcgcaaagc cgcgcctgtg 104700
gccgattacg tgctgctgca gcctagcgag gacgtggagc tgcgcgagct gcaggcgttt 104760
ctggacgaga actttaagca gctggagatc accccggccg acctgcgaac cttttctcgc 104820
gacacggacg tggtgaacca cctgctgaag ctgctgccgc tctataggca atgccagagc 104880
aagtgcgcgt tcctcaaggg ctatctctcg gagggctgtt tgcctcacac gcggccggcg 104940
gccgaggtgg agtgcaagaa atcgcagcgt atcctagagg ccctggacat tctcatcctc 105000
aaactggtgg tgggcgagtt tgccatgtcc gaggccgaca gcctggagat gttgctggac 105060
aagttctcca cggatcaggc ctcgctggtg gaggtgcagc gcgttatggg cctggtggac 105120
atggactgcg agaaaagcgc gtacatgctc gaggccggcg cggctgcgac ggttgcgcca 105180
ctgacgccac cggcggtcgt tcagggggaa agcggcgtcc gcgaggacgg ggaaacggtt 105240
gccgccgtgt cggcctttgc ctgtccctcg gtttcggact cgctgatccc cgaggaaacg 105300
ggggtcacgc gtcctatgat gagtttggct cacattaaca ccgtctcctg tcctaccgtt 105360
atgaggttcg accagcggct gctggaagag ggcgacgagg aggatgaagt gaccgtgatg 105420
tcgccgtcac ccgagcccgt gcaacagcag ccgccggtcg agcccgtgca gcagcagccc 105480
cagggacgcg ggtctcaccg tcggcgctac aaggagtcgg cgccgcaaga gacgctgcct 105540
acgaatcacg aacgcgagat tttggatctc atgcgacaca gccccgacgt gcctcgggag 105600
gcggtgatgt caccgaccat ggtcaccata cctcctcccc agataccctt tgtgggttcc 105660
gcgcgtgaac tcaggggcgt gaagaaaaag aaacccacgg cggcggcctt gctgtcctcc 105720
gcgtgaacag cctggcacgt tttggaaaac gtacgtgatc acggacacga cgagtacggg 105780
gtttctcata gacgtacttt attaggtcag ggatgacggg gaggtttcgg gccgacgtca 105840
aaaataacgt cattcgtgtt gacagggctt tctgcgtcgg agctcttttc atcttcttct 105900
gtctcgtcga cgtcatcgtc taccggcgag ggtgtccgtt gcagcaacgc gtgctcgggc 105960
gtgtgggtga aaccgatgtc gggggtgggc ggcacgatca tctgtcctag ggggtgactg 106020
cccaccggca gataggtaaa gcggtgggtg gtaaaaaccg ctttggctac ggtggtgtgt 106080
ggggagatgc agacggtggt gtgcgaagtg ttgaccaccg tcacgccggc cgcggtaccc 106140
gggagccaga tggtgggtcg gatgatgaga tccgattgac taaactggcg cacgcccact 106200
atgagggcgc agataccggg cgcgtgcacg taggccgcgt caaaatagac ggtttgcgtg 106260
tgacccggac cgatcaccag cgtctgacgg gtacgtaacg aaaagaaacg gtgttcgttg 106320
ggcggcggca agttcatgag ctgccagggt tctggtacaa aacaggggaa aacgccgata 106380
tcgccttcga tggtgcccgg aaagatggac tgaaaagtgt cgttgaggtt gacgacatcc 106440
aactgcggga cttgcagcct ggattccagc agctcgggca tgcaaacgaa ttgcgcgtcc 106500
aggcatttgt aaaaggtaat gccgaaaaaa ccttcgggga tatagaggct gacgcccagc 106560
gaggtgggca ctttgcgctc gcgtgatagc caaatgatgt gtttattgta aaaggccagc 106620
tgcgtgtggc attgtttgac gatgaaactg gaaggcatcc acttgtaagg aactttgagc 106680
ggtgacggta atggcgacga cgcttcatcc tctcccggat gctgctcttt gtcgtatttc 106740
tcctcggtcg attggggcag cgtaaatgtg gtttgaaaat cgctatcgct agcgaaacgc 106800
acgcagtaac gcatgttgac ggatttctcg gctaggatga tggagcctga tgacgatgcg 106860
gactcttcct tcattattaa cgtaggggtc tcccagaatc gctgaaaacg ggagcgcggc 106920
agccgcgaca gtaccagttg agagtcgatt cggtcggtca acatcgtaag catcgtggcg 106980
gtggtgtgat ggagtggaac acactagtat taggtctttt agttttatcg gtagtggcag 107040
agagttctgg taacaattca tccacgtcaa cctctgcaac tacatcaaag tcttctgcta 107100
gcgtatcaac taccaaacta acaacagttg caacaacttc tgcaacaact acgacgacta 107160
cgaccttatc gacaactagc actaaactca gttctaccac ccacgatcct aatgtgatga 107220
gacgacatgc gaacgatgat ttttacaagg cgcattgcac atcgcatatg tatgagctct 107280
cactgtccag ctttgcggcc tggtggacta tgcttaatgc tctaattctc atgggagctt 107340
tttgtattgt actacgacat tgctgcttcc agaactttac tgcaaccacc accaaaggct 107400
attgagggtg gacagattta cagcccggcg gtgttccggc ggggtaaggt ttacatacgt 107460
gggtgaccgg aggctaaagt tacgaatctc atctagaaac agcagcgagt ctagatagtc 107520
ccacagggga tctataaatg ttctctgaaa ccccattgat ggtgacgtag gtgtagtttt 107580
gttactatcg gaagctgttt tgttttccac gaacatggtt tcgttgtaat ataaggagct 107640
catgtcgaga gtaccgtaaa tagtgtacgg cgtttcgtta cggattagta cgtgcgtgtt 107700
tttcataaat tctgacacgg cggttcggtt gcggcttggt tcacaaaaag gattttgccg 107760
gtaacgtaga gtggtataca cccacgttgc taggtccctt aactgtgtgg ccataatgga 107820
cttcataaag ctgctatcag gacgataagc aattgtagac gtggaaaccc gccttgcggc 107880
ggtagtaata ctataagtca cgttagtagt gacgttgaga gcggcagacg ttgtatagga 107940
aaagtatggc gtagtagtac tctgagtttt cttagctttt ttttcgaatt gttccttaac 108000
gggcgcttgt ttacgtttta gttttcgcat agtgtttttt aacttggtgc cgttaatata 108060
cttggggacg cgaaatagat tccggctcat ggcgttaacc aggtagaaac tgtgtgtaca 108120
gttgcgttgt gcgtaacgta aaagcagggc ggttaaacct agaaaataaa tcgtttgact 108180
atctacgtta accttagtcg gacccacgta caatttggtg ttccaacgcg gtacattgaa 108240
aaacatgggg ttgaacgtgg tgaaattacc gcaaccttgt tcgccagtat cattacgttt 108300
ggaaacgttt agcatttcgg aaagacaagt catggaaggc acagtaccac aaggtggggg 108360
tctgaatgtt atcgttttag ccgtatgatt gtactgtgag taaacgtatt ttgcgggttt 108420
tctaagctgg gtactataaa aatcaaacca cagataggtt atactataat tctgaatggg 108480
gcccgctaaa atgtagtatt gtggaaactc tgtcatgttc atagtgagat ttttaaccgg 108540
ttgtttactt acattgtatt ttgtagaaat agtcgtttct agttgtctca aaatttctaa 108600
cttaagctga tctaatttat atttgcctat cttagacagt accaagcccc tccaaggacg 108660
attataaagc gcttttgaca taactttaca gtttatgaaa gaaacaagca agaaagatat 108720
agatattaga aacaccatct tagggacgtc tctcaccatc atctcttttc tccccatgac 108780
agaggaggag accccgcacc gtccgtctgc cttgtggttt ggcttgcctg cgtgtactca 108840
ctgctgattc tggtcgtttt gctgctcatc taccgttgtt gcatcggctt ccaagacgac 108900
ctagtctccc gcaccttggc tgtgtaccaa gcttgtatcc agggcccgat atgtaaccag 108960
acccataaca gtacctcgta aataaagacg cacagacctc acgcatatag taccatcaca 109020
ccgtgtggcg tgtactttat tacaacgagc aagagtgccc ctaagtattg gggcccgtac 109080
cgttttagaa gattttgtgt gaatgtcttt aacttttctg tcccttttct cataaactgt 109140
caggttctac agtcagcatg tcttgagcat gcggtagagc agatagatgc cgatgatggc 109200
cgatagcgcg tagacggaca tcatgaggag acgactgtcg gtggcgtcca cgacgacgtc 109260
agttacttct aggaccgtac cgtttttcaa aagcatgagg tagtgagttc gcggagatga 109320
gaccaccact tcgttgtagg gatccagggc gaaaaggacg tcgtccgagt cgtgcatgta 109380
catgatgttg atgacgcctt gcgtgtcgtc gtattctagc agggcgcttt ggcaaaaggc 109440
gcagttttct agtgaaatgt tgagcgccgc tgtgatgctg tgtgtggtgt gcatgttgcg 109500
cgttagttcg catttagttt gactgtccgt ttgggtgatg atgaggctct ggcctacgac 109560
ggtggtggag acagggtagg agataccttt gatcaggtac tggtttgtta cgacataact 109620
gacgtgttcg gagacggtta gcgcggagaa ggattcgccg agcggcagac aaaacaggtc 109680
ggggaaggtt tccagcgtgc ttggttgcat ggtagatagg atggagaggg cggcgggaac 109740
ggtagcagga acggtggcat cggggaagag acgcgtgagg cgttcgagcg agtgatcgcg 109800
tcgcccgcta ctggaacagg gtgtgtacag gtcgctgagg tattcgtggt gcggatgagc 109860
tagcaactgc gtaaagtgtg atagctcggc caatgaacag aggcccgttt ctacgatgaa 109920
gatttcgcgt ctctccgtcg tatgtaccaa catggagtgg acgaggctgc ccatgaggta 109980
gagttcttgg cgcgcgaagg ctgaaagaaa agaggccagg tgcgttttgt gtaattgtag 110040
ggcaaagtcg gcgatctgtc gtagtgccca ctggggaatg agatgttgct gattctgttt 110100
agaaagtatg tagaccaggc gtacgaggct ggtgatgtcg gtgatctggt ccggcgtcca 110160
gagggctcgt ttggccaggt ccacggctgt gggatatagc agcaatgtgg tgcgtggtgg 110220
tgtttgtgag aggcaggtga tcataaattc ttgtatttgt aagagtgcgg cctggcggtc 110280
tagggctcgt gggatggaga tttcggtgcc ggcctcttct tgtcgggctg ccgcgaacag 110340
tgctaatgcg taggcgaagg ccatttctac cgtgcggcgg tccaacattt gacatcgacc 110400
gcttttgagt acgtctacag cgtaacggtg aaagctgtta cgtaacagtg cgctgaggtc 110460
caggtagttg aagtcgagtg cggcgtcgag aaagtccgag tctttgagat aggagtgacg 110520
gtttagttga gctttcttaa ctagtaccag gagctcgtgt ttttcagttt gtcgtagtat 110580
aaagttgtcg cgttgatagg gcgctttgaa gagtacgcgt ggaagatgac cgaagataag 110640
cagcatgggt gtgtcgtcgt ctatagatac cgtaactacg aagaagtcct cggtcagtgt 110700
gattttaacg taacgtagtt cgtccatgag gtaaaagccc tggtgcagac agggcgtaac 110760
ggtgctgaaa agcagatcgt gtccatcaaa gaggatacag gtctggttaa agtgtggccg 110820
atgtagtccc gaggtggtgt gcgatccctt ccagtcgtgt ggagtggttt ggggtggcat 110880
ccaaacgtga ggtattgaca gatcaatggg cggtggcacg gtggtgggct gctgacccag 110940
gctgtcttgt gccttcagct gctgcgaaaa agatcggtag ctggccaggt ctttggatac 111000
caatgcgtag gtgttaagtc tctgttggta tctttctagg gtttcggtca gatctacctg 111060
gttcagaaac tgctccgcca gaggacccgc aaaaagacat cgaggcatat ggaatacata 111120
gtattgatta tagctttgga aaaagttgaa actgatggcg ttttccctga cgaccgtgct 111180
gttacggagg ctgctgttgt aggtgcactg ggtggtgttt tcacgcagga agcggatggg 111240
tctcccgtag gtgttgagta gtaggtgaaa tgcgtgaggg tccagcgctt cggatgcggc 111300
gtccgcgcca tatcgttgcg aaggtaggtg actgaggagg tagacggtga agacagtgag 111360
gtaggggggg aggccgggcc gcatagcgcg gctgcgccgc tgggttcagc ggcgtgatcc 111420
aggtggtggt tggcgttaca cccgagagaa ggagagaaag gatcccagga aggggcaccc 111480
gggtgtggcg ctacgggtta caaaagtcgc gtctctgtct atttaatacg atgtcattgg 111540
ccgctgcgaa ggaagaagag gggacacgcg ggtaagccat gccgtccggg cgtggggacg 111600
acgctgattc gacggggaac gctctgcgga gattgcctca cgtgcgtaag cggatcggta 111660
agcgtaagca cctggacatc taccgtcgcc tgttgcgggt ctttccctcg tttgtggccc 111720
tcaaccgcct gttgggaggc cttttcccac ccgagctgca aaagtaccgt cgccgtcttt 111780
tcatcgaagt acgattaagt cggcggattc ccgactgcgt gttggtgttt ttaccgccgg 111840
actctgggtc gcgcggcatc gtgtattgct acgtgattga gttcaaaact acgtactcag 111900
acgccgacga tcagtccgtg cggtggcacg ccacccacag cctgcagtac gccgagggcc 111960
tgcgccagct caagggcgcc ttggtggact ttgattttct gcgtctgccg cgcggtggcg 112020
gtcaagtctg gagcgtagtg cccagtctgg ttttttttca gcaaaaggcc gatcgcccat 112080
ctttttaccg ggcttttcgt tcgggccgtt tcgacttgtg taccgattct gtcctggact 112140
atctgggacg gcgtcaggat gagtctgttg cacacctttt ggcggctacc cgtcgccgtc 112200
ttcttcgaac cgcacgagga aaacgtgctg cgctgccccg agcgcgtgct tcggcggttg 112260
ctggaggacg cggcggtgac aatgcgcggc gggggctggc gcgaggacgt gctcatggac 112320
cgggtgcgca aacggtatct gcgtcaggag ctcagggatc tgggtcacag ggtgcagact 112380
tactgcgagg atctcgaagg gcgcgtgtcc gaggcggagg cgctgttgaa ccagcagtgc 112440
gagctcgacg aaggaccgtc gccgcggacg ctgctacaac caccgtgtcg tccgcgttct 112500
tcgtccccag ggaccggcgt ggcaggagct tctgccgtcc cacacggtct ttatagtcgg 112560
cacgatgcca tcacgggacc cgccgccgcc ccgtctgacg tggtcgcccc gtctgacgcg 112620
gtcgccgcgt cagcggccgc cggtgcttct tctacctggc tggcgcagtg cgccgagcgg 112680
ccgttgcccg ggaacgtacc tagctacttt ggaatcacgc agaacgatcc ctttatccgc 112740
tttcacaccg attttcgcgg cgaggtggtc aacaccatgt tcgagaatgc ctctacttgg 112800
actttctcct ttggtatctg gtactatcgg ctcaagcggg ggttgtacac gcaaccacgg 112860
tggaaacgag tgtaccatct ggcgcagatg gacaactttt ccatttcgca ggagctgctg 112920
ctcggcgtgg tcaacgcttt ggaaaacgtg acggtgtatc cgacgtacga ctgtgtactc 112980
tccgatttgg aagccgccgc ctgtctgctg gccgcctacg gacatgcgct ttgggagggc 113040
cgcgatccgc cggactccgt ggcgacggtg ttgggtgagc tccctcagct gttgccgcgt 113100
ctggccgacg acgtgagtcg tgagattgcc gcttgggaag gccccgtcgc cgcgggtaac 113160
aactattacg cgtatcgcga ctcgcccgat ctacgctact acatgcccct aagcggtggt 113220
cgtcactatc acccgggcac ttttgatcgt cacgtgctgg tgcggctttt ccacaaacgc 113280
ggcgttattc agcatttgcc gggctacggg acgataacgg aggagctggt gcaagagcgt 113340
ctgtcgggcc aggtgcgcga cgacgtgctt tctctctgga gtcgacgtct gctggtcggc 113400
aagctgggtc gcgacgtgcc cgtctttgtg cacgaacagc aatatctgcg ttcgggcctg 113460
acctgcctgg ctggcctgct gttgttgtgg aaggtgacca acgcggatag cgtcttcgct 113520
ccgcgcacgg gcaaatttac gttggccgac ctgctgggtt cggatgccgt agccggcggc 113580
gggttgcccg gggggcgcgc gggcggcgaa gaggagggct acgggggacg gcacgggcgg 113640
gtacgtaact ttgagtttct ggtacggtac tacatcgggc cgtggtacgc gcgcgacccc 113700
gcggtcacgc tgtcgcagct ctttcccggc ctggctctgt tggccgtgac cgagagcgtg 113760
cgcagcggct gggatccctc acgtcgcgag gacagcgccg gaggtggcga cggcggcggc 113820
gccgtgctca tgcagctcag caagagcaac cccgtggccg actacatgtt cgcgcagagc 113880
tccaaacagt acggcgattt acgtcgctta gaggtacacg atgccctgct ctttcactac 113940
gaacacgggc tagggcggct gttgtcagtg accctgccgc gtcaccgtgt gtccactctg 114000
ggctcgtccc tctttaacgt caacgatatt tacgaactgt tgtacttttt agtgttgggg 114060
tttcttccga gcgtggcggt gttgtaattt ccaccacgtg tcgctcgctg cataaagggc 114120
gaacgtcctc ggagagggta tattcgttcg gcgagagcgg gcggcggtgg tgggtatgtc 114180
cccttctgtg gaggagacta cctcagtcac cgagtccatc atgttcgcta ttgtgagttt 114240
caaacacatg ggcccgttcg aaggctactc tatgtcggcc gatcgcgccg cctcggatct 114300
actcatcggc atgttcggct ccgttagcct ggtcaacctg ctgactatca tcggttgcct 114360
ctgggtgttg cgtgttacgc ggccgcccgt gtccgtgatg atttttactt ggaatctggt 114420
acttagtcag tttttttcca tcctggccac catgttgtcc aagggtatca tgctgcgtgg 114480
cgctctaaat ctcagcctct gtcgcttagt gctctttgtc gacgacgtgg gcctatattc 114540
gacggcgttg tttttcctct ttctgatact ggatcgtctg tcggccatat cttacggccg 114600
tgatctctgg catcatgaga cgcgcgaaaa cgccggcgtg gcgctctacg cggtcgcctt 114660
tgcctgggtt ctttccatcg tagccgctgt gcccaccgcc gctacgggtt cactggacta 114720
ccgttggcta ggctgtcaga tccctataca gtatgccgcg gtggacctca ccatcaagat 114780
gtggtttttg ctgggggcgc ccatgatcgc cgtactggct aacgtggtag agttggccta 114840
cagcgatcgg cgcgaccacg tctggtccta cgtgggtcgt gtctgcacct tctacgtgac 114900
gtgtctcatg ctgtttgtgc cctactactg cttcagagtc ctacgcggtg tactgcagcc 114960
cgctagcgcg gccggcaccg gtttcggcat tatggattac gtggaattgg ctacgcgtac 115020
ccttctcacc atgcgtcttg gcattctgcc gctctttatc attgcgttct tctcccgcga 115080
gcccaccaag gatctggatg actcctttga ttatctggtc gagagatgtc agcaaagctg 115140
ccacggtcat ttcgtacgtc ggttggtgca ggcgttgaag cgggctatgt atagcgtgga 115200
gctggccgtg tgttactttt ctacgtccgt ccgagacgtc gccgaggcgg tgaaaaagtc 115260
ctccagccgt tgttacgccg acgcgacgtc ggcggccgtt gtggtaacga caaccacgtc 115320
ggagaaagcc acgttggtgg agcacgcgga aggcatggct tccgaaatgt gtcctgggac 115380
tacgatcgat gtttcggccg aaagttcctc cgtcctctgc accgacggcg aaaacaccgt 115440
cgcgtcggac gcgacggtga cggcattatg agcggcggcg ctgtacggca gcggggagaa 115500
aagtggcaga taaatcacgt caggttcaca cgtcgttagc cagcgtcggc atatgaaggg 115560
cgcgggcggc cagtacggcc tctgggctga gacaggacga ggcagggtga gaaagaggag 115620
gatggggggg accggggtgg tggtgctgct gctgttgtgg gtgcggacgg tgcgggtgcc 115680
gggacagcgt gccggcgaac gttctgtaat cttccataat aaaagtaaaa atgcccgtct 115740
cgtgtcgact ccgctggatc tcgaaggcgt cgggggtaat gcgcatcttg ccggtgccga 115800
tgagataaaa gtaccacatt ttttgacaga tgatgcgaat caagggttcg tacgcttcgg 115860
caccccagtg gcgcgtgaag aaggccgcca gacgaaacaa gcggtgtccg tagagcgtgc 115920
ctagggagaa gaggatgttg ccgttgcgcg ccaggtcttc ggggaaaacg accggcaggc 115980
cggtgtggcg ctgcacaaag cgcgtcagca gtccgccgct caagcgcggg tgacacaggc 116040
gctggctgag acgggcggcg cgcgtttcat cgaacacggc cgcctcaaag tccagccccg 116100
ggaaggcctg gcgcagttcg cggtacagat gaggccagta gggttgcggc gtcttgcgac 116160
taagcacggc gtggtccgag acacccaggt tgttcatggt ttcgcgcagt agcagcgttt 116220
cgagaccgcg gtgaaagagg aggacgcaga tgaggcgtac gatcttgagt tcttccaaac 116280
gcagcgagct cagcggctgt ccgcgcgaca tcttctcgct aatctgtaat attagatgat 116340
tggcgcaagt aaaggagaat ttgcccgtgc ggacccgcgg gacggcgggg ttctcttcgt 116400
cgcgggccat catcgttcgc tcggtgagcg ggtagcgacg gtgacgacaa tgacgatgga 116460
cgagcagcag tcgcaggctg tggcgccggt ctacgtgggc ggctttctcg cccgctacga 116520
ccagtctccg gacgaggccg aattgctgtt gccgcgggac gtagtggagc actggttgca 116580
cgcgcagggc cagggacagc cttcgttgtc ggtcgcgctc ccgctcaaca tcaaccacga 116640
cgacacggcc gttgtaggac acgttgcggc gatgcagagc gtccgcgacg gtcttttttg 116700
cctgggctgc gtcacttcgc ccaggtttct ggagattgta cgccgcgctt cggaaaagtc 116760
cgagctggtt tcgcgcgggc ccgtcagtcc gctgcagcca gacaaggtgg tggagtttct 116820
cagcggcagc tacgccggcc tctcgctctc cagccggcgc tgcgacgacg tggaggccgc 116880
gacgtcgctt tcgggctcgg aaaccacgcc gttcaaacac gtggctttgt gcagcgtggg 116940
tcggcgtcgc ggtacgttgg ccgtgtacgg gcgcgatccc gagtgggtca cacagcggtt 117000
tccagacctc acggcggccg accgtgacgg gctacgtgca cagtggcagc gctgcggcag 117060
cactgctgtc gacgcgtcgg gcgatccctt tcgctcagac agctacggcc tgttgggcaa 117120
cagcgtggac gcgctctaca tccgtgagcg actgcccaag ctgcgctacg acaagcaact 117180
agtcggcgtg acggagcgcg agtcatacgt caaggcgagc gtttcgcctg aggcggcgtg 117240
cgatattaaa gcggcgtccg ccgagcgttc gggcgacagc cgcagtcagg ccgccacgcc 117300
ggcggctggg gcgcgcgttc cctcttcgtc cccgtcgcct ccagtcgaac cgccatctcc 117360
tgtacagccg cctgcgcttc cagcgtcgcc gtccgttctt cccgcggaat caccgccgtc 117420
gctttctccc tcggagccgg cagaggcggc gtccatgtcg caccctctga gtgctgcggt 117480
tcccgccgct acggctcctc caggtgctac cgtggcaggt gcgtcgccgg ctgtgtcgtc 117540
tctagcgtgg cctcacgacg gagtttattt acccaaagac gcttttttct cgctacttgg 117600
ggccagtcgc tcggcagtgc ccgtcatgta tcccggcgcc gtagcggccc ctccttctgc 117660
ttcgccagca ccgctgcctt tgccgtctta tcccgcgtcc tacggcgccc ccgtcgtggg 117720
ttacgaccag ttggcggcac gtcactttgc ggactacgtg gatccccatt atcccgggtg 117780
gggtcggcgt tacgagcccg cgccgtcttt gcatccgtct tatcccgtgc cgccgccacc 117840
atcaccggcc tattaccgtc ggcgcgactc tccgggcggt atggatgaac caccgtccgg 117900
atgggagcgt tacgacggtg gtcaccgtgg tcagtcgcag aagcagcacc gtcacggggg 117960
cagcggcgga cacaacaaac gccgtaagga aaccgcggcg gcgtcgtcgt cgtcctcgga 118020
cgaagacttg agtttcccag gcgaggccga gcacggccgg gcacgaaagc gtctaaaaag 118080
tcacgtcaat agcgacggtg gaagtggcgg gcacgcgggt tccaatcagc agcagcaaca 118140
acgttacgat gaactgcggg atgccattca cgagctgaaa cgcgatctgt ttgctgcgcg 118200
gcagagttct acgttacttt cggcggctct tccctctgcg gcctcttcct ccccaactac 118260
tactaccgtg tgtactccca ccggcgagct gacgagtggc ggaggagaaa cacccacggc 118320
acttctatcc ggaggtgcca aggtagctga gcgcgctcag gccggcgtgg tgaacgccag 118380
ttgccgcctc gctaccgcgt cgggttctga ggcggcaacg gccgggccct cgacggcagg 118440
ttcttcttcc tgcccggcta gtgtcgtgtt agccgccgct gctgcccaag ccgccgcagc 118500
ttcccagagc ccgcccaaag acatggtaga tctgaatcgg cggatttttg tggctgcgct 118560
caataagctc gagtaagaga gacgctatat ttagggcttc cctctctttt ttttctacac 118620
cgtgataccc taataaagca caccgcggtt attatcaacg tctctgtgtt tttattattt 118680
agaaataaat acagggaatg ggaaaaacac gcgggggaaa aacaaagaag tctctctcta 118740
gatgcggggt cgactgcgtg gggtgctgga agtggaagcg gtgctgatgg gtgagggtcg 118800
tggcgcgggc acggaccgca acgtgctgct gatgtctgcc gcggtacgca cgtcgccgtc 118860
catgtcgctg cgcagataag aggtaggtcg tagtgcggcg tgctgcacgc tcaccgttaa 118920
tggtaccaag tcgtcaaggc tcgcaaagac gtgccacgag gggatgacga gcgtgagagc 118980
cccgttgtta ccgcttcgac gtctttgtcc ggtcaggatc agtgccgggg acagtccggc 119040
ttgggtgtcc gagtcctcgt cgccgctggc ttcctcgaag ccggcaaaca tggcttcgga 119100
caggggggtc ggcgtcggtg tggaggagag gtcatcttcg tcgtcctctt cctcttcttc 119160
ctcctcttcc tcggtgggtg gtaatccggg ggactgcggg agaaactcgg agacggcgcc 119220
gcgcatgacg ttgctccgtg gaaagagacc ggcgcgcagc tgcacctggg gacgcttgat 119280
tttgtccggt ttaccgggtg tgagagtcca aaacccacgg cggaaaaagt ggatgcggcc 119340
tagcggctgt cggtgttcca aatgaacggc ctgatcgccg gtcagcgtga cgcggagggt 119400
gattcgcaca cgatcgggta gcgggccggc ttctatggag acgcccggga tgttttccgg 119460
gaaaaagatg gtgtcgtgag tctgattggt ctcgaaagca ttctggatct gcacgatgta 119520
ctcgggatgt atgcgcgtca gcgtaaaact tttgggaatc aacagctgga agccgttgtc 119580
cggcaagcgt cgtaggtgcg ggtacggatt gtgtcgcgcc accacctcgg cgcgatgcgt 119640
gtaaaccgaa aagtgcagaa acacgctggt cggcgggtgc ggtgagtcgt gatgcagaaa 119700
cagcatgatc cattggcctc gttcgtccgt ctccgttttg tggatgtacg tgttagggtc 119760
cgaacaggcc agctgctcca gggcgtctac cagcgtcagc gggatggcgc cggcgcgaaa 119820
ggcgaactgg ctgacaaaga tctgccctgc ctccaaactg ctgtcggttc tgcggcgcca 119880
gttcggcgtt acggtcagtc gcacggccca gtggtgagcc gtgcggcgga tgatggcgcg 119940
cgcttccatt cgcggccgat tttcttcgcc gccgcgccgc tggctctgaa agaggtgcag 120000
tccgctaacg ggcacgcggt ccagcggcag cgcaaaggcc agtaccgaga ccgtgttgtt 120060
ttctgagcct ggcgtcaggc gtcgtgggcc aaagttgttg aggtccacca gcagtcggtc 120120
ctgttcgccc accacgcagc ggcccttgat gtttaagtcg gtcaggtcta cggtgtcgtg 120180
cggagatttg ttctcctgaa aacagcagag aaccgagggc cggctcacct ctatgttggt 120240
acgcaggtcc aggagtcgca gacgaccggc ttccagcgag ccgccttcca cgttggtgat 120300
gagccgaagc acctggcagt gcaggcgacc aaagcttccg ctggcggctt cggcctcgct 120360
gatcgcggcc gcttccgacg agggtccctc accgggcgag gacgatgcct gagacattgc 120420
gaaggcggga tggggggagg gtcaggggat gcgcaaaggt gaacgggtct tcgtgggagg 120480
tcgggaaggg ttccggcaac tgtcgcaaat atagcagcgg tgacaggtgt ggcggccaaa 120540
agttgcgtgt ctgagtggac gtgggttttt atagagtcgt cctaagcgcg tgcgcggcgg 120600
gtggctcaac ctcggtgctt tttgggcgtc gaggcgatgc atggcccggg caaggcgtct 120660
tgccggtggc ggcgacgttt gggttgcgca gcgggctgcc atacgccttc caattcggcg 120720
aagatgcggt agatgtcgtt ggcgtcccag aagaattcct ggtacttcag attctgaccc 120780
tgaaccgtag ccaccatggg caccaggttg cgggccagga tgccggcctg ccagggcggc 120840
caggtgaaca cggccggatt gtggatttcg ttgtcggaat cctcgtcggt gtcctcttcg 120900
ggcgcgacgg tggactcggc cttaaggcgg ccgcgtgtca taacgcccga cgtgcacgcc 120960
gtcgccgagg atgctgattt gcgtttgcgg cccgcggaag tggaggcgcc cgccatggcg 121020
ccgccgccgg tgacgcgggg cgtcttgcgc tcggtggtta cgagttcttc gtcggagtcc 121080
gatccgctgg tccagacgtc gtcgtcgccc tgggcggcac cctcgtcgtg ccggtcccag 121140
gtgtgtcggt actcaagctt gccctggatg cgatactggc tggtgaaggt ggggtgctcg 121200
ctgtactgag gcccgcgctg cagcagcaag tcgatatcga aaaagaagag cgcagccacg 121260
ggatcgtact gacgcagttc cacggtctcg cgtatggctt gtacctccag gaagatctgc 121320
tgcccgttca tcaacaggtt acctgagatg ctcaggcccg ggatgctctt gggacacagc 121380
agcccaaaat gctcgtgtga ggtaaaagcc acatccagca tgatgtgcga gatcttgccc 121440
ggtttgatta tcatattttt gggacacaac accgtaaagc cgttgcgctc gtgggggcgc 121500
atgaagggtt gcgggttgcg ggtcatcgtc aggtcctctt ccacgtcaga gcccagcgtg 121560
acgtgcataa agagcttgcc ggagggcacg tcctcgcaga aggactccag gtacaccttg 121620
acgtactggt cacctatcac ctgcatcttg gttgcgcgcg tgttctccat ggagcaaacc 121680
agctcgtgcg cgcacaccac gtgccgcagt gccacgtcct tggtgggaaa cacgaacgct 121740
gacgtgtagt agacgtcggg ctctttccac tggttctgct gacgcgtcca ggccagtccc 121800
gagaccgtga gacgcgcctg ccacatctgc ttgcccgacg cgtgaatcac agcgtcagct 121860
acgggcaggt gtcggtgttt gcgctcggcc gccgacgggt agtggtgcac gttgatgctg 121920
gggatgttca gcatcttgag cggcagcgcg tacacataga tcgacatggg ctcctggctg 121980
gggcagatgc ttcggcccgt ggggttgtgc acgttgaccg acacgttctc cacctcgctg 122040
cccgtaaagt acgtgtgctg cacctgcagc tgattgtcgc cgcggtggca tggcgtcgag 122100
tcgggcgtgt actgcgatac caagatcagc gagggctggc tcacgcgtac gtggataccc 122160
gtctgcagga gtcgcgtctc gtgcggcagc accggcgtat cgccgcgact aaacacggct 122220
ttcagcacgt gccccgaaat gggacccagt acggatatca tttcgggaca acggcgaccg 122280
cgcgactcca tgctgcctgc gcgtacgggt gtaggcgact gagcggcgcg ccctctgcgg 122340
ccgccgcctt acataggcag gcgaccaaac gcggaacccg aaataaaaac gttctacaca 122400
gagacaaccg cggattattg agtgtctttt tttattacaa aaaaaagagg cgaagcccca 122460
ccgtcaccac accccatcac acaccaccac cgattttttt ttgttttaat cccgtatggc 122520
gcggacgcct agtgtccgtt tcccattatc agggtcctct gtttagagat cgccgcagac 122580
catggctaaa gtgacaggac tcgtcttctc tgtcgtattt tccgtaagct tacagtcttg 122640
cggttccgtc tccggggacg ccagtcgcat gggcagcagg tcctccagcg cgatggaagc 122700
gcccagcacc gagagctgct gttgcgacgg cgaatgggat gtggaccgcg agtgtagcgt 122760
ggatttgact tggtgcgtca ttgctgacag gcaaccccga ttcagcgtat gctttgacga 122820
gataaaatag aggcgcccca ggagcgcgtc ccgtgggaac gtggcgccgt tctcgtcgct 122880
caccagtacg gttaattcca accaggagcg cggtagccag accgtaacgg gcattttgag 122940
tccctgacgg ttgtgtggta caaaaacacc cagataaggc ccgtaaaagc ggcggtagat 123000
acgtaacgtg tgcgagttct tcagcgtcaa ttcgtaaggg acgcgcacct ccagtccctc 123060
gtccgccgcg ccggagcgtg gcggtacaaa gtaaggcagt ggcgcgtccg aaaagaaggg 123120
tcgtcgcacc gtttcgcgtc gcagccgcag gcgaaacgcc actgggtcgg ctggcgcctc 123180
ggtgcggtcg caggtcacgt tgaaacgtaa tatgccgtct tggtatagcg tgagtgacga 123240
cagcgtcagg tccggcggtg attcgttcgg gtctagctcc aatcgtccaa agacggaggg 123300
tcccaatgtc ttggccgtgg tttccgagag gcgcgccgag atacggctgg tgagtccacg 123360
cggccccgag atgccgcctt ccactcgatg ccagcacagc gcgtgtcgta cgcgcaccgt 123420
cagcgtgggc gtcagatccg cgtccgttga ttccgcggta tcagcgacgg aagccgcgtt 123480
ctccgttacg ttgtttatat ccagcgtcgg ctcgaacgtg agttctggca gatgcagcgc 123540
cagacagtcg tgtaacgccg tgtgatgcgc ggctttacgt cgtagcggta gccgtttcaa 123600
cagcggcgtg atgatacgga gcgcgaagag attgagtgat aggcgcacga tggccatgcg 123660
cgtcagttgt tggtcaatta ccgagcgcag gatatggcag cctgggcgtg cgggaaagag 123720
agagaaggcc gggcgcacgt cagaatcctc gttagagacc acgcatagaa tgccgcgttc 123780
acgatcgtcg ttgcggtcat cctcgtcctc ttctttcttc tcttgttttt cctttttttt 123840
ctcgggctcg tgggaagccg ccgtttcttc ttcttgcaac gtcgcggggg cggtttgaga 123900
ctcgtcgttc gcttccccca attgcagcgg cgtagagagc agaatctgga agggatcccg 123960
caattcttcg ggtcggaggt cgaggtgcaa ctggatcaga tggtaggtgc cgcggtgcac 124020
ccgaggctga cggatgtcgt gtttatccgt cagtgtgagg atggtctgcg gcgagccgct 124080
gtacttgtcc agctcgtccg gcgttttcag gaggagactg tcgtcgtcgg tactggcgac 124140
gcccatcatg gtcgtggtgg tagtggtggc gaggaaagtg agcggcggcg ccgacagagc 124200
tcggcgttgg cggcggcatt ttccgctgtg tcggctgcta ttgctgccaa cgccaccgcc 124260
gccgcctcgt ctggctcgtg gccggcgggc ccgattccga aggttggggt cgacgcgtgg 124320
catgcttggt gtctgcgggc gcgagagggc cggctcagcc tttaaatatg caggtcgcgg 124380
atttgttatc gggtgaaacg tcacacaccg tgaagacgac ctgttcgcgg atgaggtcat 124440
ccagctgtcg cagcatgacg aaaagcgccg acagccgcgc gatctcgtcg tcgggcgaca 124500
cgtgctgcgg ccgcgcgggc gtgcgcggct cgccgacgct gcgctcgcgg tccagccgca 124560
tcagcagctc ctggcacttg acgagcagca tggagctgtc ctctagcgcc aacttgcgca 124620
cgtaggtcat ggtcagctcc gaggctaggt tggccaccat ggacatggag aggcaggcgg 124680
tcttcatgtc gatcagcagg tgctggtcga tgaccggatc ggggatggtg aaggtggcgt 124740
cgcgaaaagt aatggtctgc agctgctgca cggcagcctt tacctcctcg tacgaacggt 124800
cgagcgagaa gaggcccatg atgagtagtc gctggttgat ttccagcgcc agtggcatgg 124860
gtacgatcca gggcagcacc agctcccact ggcccagcgt cagcaggttc tcgcgcgcca 124920
gcggtccgtg gaagagcggc ggcagcacgc atagcgcgtc gcccttctcc caagtcacgg 124980
gtcccgtgtt gaggacggtg tagagcagtc cgtgcgtggg tacgtgtagg aggatctggt 125040
tgccttctac gcgccgcatc aacgtcagcg tcatattgcg cagcaggccg cgcagtcgta 125100
cgtagccgcg ggtgtgatct acgaactggt gtaggcccag ctggtagtgc ttgatgagat 125160
gtagacgttg cggaatgggc acaacggccg ctactagctt ggtcagtttg cctacgtcgg 125220
cgatgctgag cttgtggtcg aaagtgcaga agatgttggc ctccatggcc gccatagcgg 125280
cggtgaaatc ctggccgcga cggaggagag gcagagacga acaacgtctg caccgggcgc 125340
ggcgtcagag cgagcgtggc gcgtccgggc ccgcgtttgc gtctaggtga ctcgccgcta 125400
acctgcggtc gtcgccgtcc tcctcaccgg acggcctcac gagttaaata acatggattg 125460
ctgcagcggg atgatttcgc ctacgacgta gttaccaaag tgcgtttcgg acgtagcaaa 125520
agccccggcg ccacccttga gtttggtctc catcagcgcc agcgtggtgg tgctgaggat 125580
cggtagcgct tcctgcgtca gacggcacgg gttttcgatg agttgttccg tgccttcgac 125640
gcagacgtac tgcgtgtccg tgtcgccgcg gatgcagtcc ttggcgcgta gcaggtactc 125700
gtcgatggtt ttgaagagcg ttttgttggc cgcgataatc tcttctgtgt taaagtactg 125760
cgcgcaaggg ctgtagaatt tggagttgta gcctagacgt tcgcgatgtc gggtgttgta 125820
gagtacgtcg ctcagacagc cggcttgcga ggcccagggg ttgtgtgtgg ccgcgaaagt 125880
ctgtgcgtcc gcttcgcgat ggtcgtagat ggccttggtg gcggcctccg tgtcgtacgg 125940
atcgacggcc agcatgcagg aggcacgccc gcgcgggttg ttggggatct taaagtaatt 126000
aacgtccatc gtcaccggcg taaggattag ttcgcacgcg gccttttgtc cgtgcaccgt 126060
ggcggcggca ttgcgctcgg acatgctgcc gaacgtcagc atagagatgg tctccgtgtc 126120
taacagttgc ggccgttcta cgccggccgc gtgccggatc cagcggtcca cctcgtcgtg 126180
ccggtacacg ttcataggga agacgcgaaa gaggtcctgc acgcggacgc ccatgtcggt 126240
tcgcacgcgg tttacgtagg ctacgcaggt atttgacgtg taacccagac ccatgtctac 126300
ggtgttaatg ttctgcgtga cgtggtacgt agtgctgatg tcgcgttcct ccttggtcac 126360
gatagggttg ttgatgataa ctgacgtgca tgatttgccg ctgtagagca gcatgtccac 126420
ctcgaaggtg tcggtgcgta cggccgtgag tgcgaatccc gggtggatgt gcgccttggt 126480
ctgcagcacc agtgaaactg gtgagatttt gtataacatg gcggccagcg tcatgactga 126540
gtgcaacacg ttgggacagg tggccgagta acgcgaaaag ggcgagcgca gccagttgtg 126600
gtactcgtgc gcgaaggctg tgggtagcgg gaaaccaccg tcgtgacggt gatagtgcgg 126660
gaactcggtc acgtagcgtt taatgtcgtc gctcaacgcc gcgcagatgg tggggtttga 126720
gtagaaacgg tggaaaggta cgggtaggct gtactcgatc aacgtcttag gcgccgtcac 126780
gacgcagcag ccgttgtaaa gcacgtgctg acgtgagata aagtccggca ggccctgacg 126840
ctgcgcgtgg tccagaggcg cgcgcacttc gagcaccttg acgtgctcgc ccacgaattg 126900
cacggccaaa aacagttcac gacaggcctg cagcagcggc gtatgtgcgt cggtggcgac 126960
gtcctccacc agctcggtca gcatctcgcc tacggcttga cgttgcgccg ctatcgagtc 127020
ttcgggggtg acaccgcttg tgctctcttt cgacgtcgta cctgacgtgg agaccgcggt 127080
ggcggccggc atcaggagaa acgccggtcg gtaaaagagg tctactagca gcgtcttgag 127140
gttgagtccc aggccgcagg cccggttgtt ggtcatggcg ggcatgaggc agagataaaa 127200
gaccttttgt aacgtccatt cgtcgtcggt ggcacggtaa tcgtccacaa acagcggctc 127260
gtcggcatcc atggcgccca aacgcggtac gtccgaaacg ccgtggtgtc gcgcctcgat 127320
gttggccggg ttcaacggtt gccggtcggc cactacctgt acgccttcca tgttacgcgg 127380
caggtgcgta acgaaggggg gccacagccg gtggtcgtgc agcgcgttca cgtaagccga 127440
tagcggttcc tcagccagtt gaccgttgtt aagtcccggc agcgctgaga tgcgcgttac 127500
cagacgcagc acggcgacca gattgcggta gtgaaagagc aactgcggtg gtagggcgcc 127560
atcagccagg tgttcggcga tcaacgtcac cagcgcgtag ctgtgcgcaa aaaccagcag 127620
ctgacgtgtg tgaaacatgt tgacgataca acgtgctacg aaagtgcgga ttagcaaaaa 127680
agcgtcgacg ttgccgtgta ccagcacgtc gaccaggtag caaagctcgg ggtaattggg 127740
gcttgtcacg gtggttttga aaagtcgcaa cgtctcttcg tagtcgggtg gtggccgcag 127800
tcgcatgtgt tccatgatct cccaggtgcg cagttcgtgg aaggggcccg gtgccagtcc 127860
atctggcaaa ttaccgatga cgatacgcgg tgtacacagc gccaccgttt cgctgttttc 127920
ctggcagtgc gtaaagtcga agaaggggtg cagctcggtg tagagcgtga tgttgcccac 127980
cttgtagaag tcggtgacca caaagtcctg cttcatttcg ttcaccgtgc gcgggacctc 128040
gcgtcgtacg cggtaaaaat gcggtatgcg gcgcgccgca ccgcccatgg gttcctgctg 128100
aaaacgacac tcgagcagtc gttgcatggc gggttccgag ggcggtccgc gttccgtgaa 128160
ggtctgtaga cagggcgcgg gctcgtgcag caccgggtgg cacagcgtct tgagcgcgtc 128220
cacaaagtct attttttgta cggcacggtc ccggtttagc aggtaggccg tggtgggcaa 128280
cgcgttgcga acggtgtcgt taagcttaac tttgctttcc accgtggtgt aaccgcgatc 128340
ctcgggcaga tacagcccta cggggaagaa aaacgtcagg tccacgttac gttctagcgg 128400
atctttggta tcggtgtttt tgtagacgcg ccgcaagttt tccataatca ccgttttttc 128460
gcccagtcgg atcacgtcca tgctcagcgg cgttaagctg tgcgccccgg cctgcgaaag 128520
cgagtcgttg ggcaaatgcg gttggcccga agtcagatga gccttgtacg agttgaaatc 128580
ggccaggatc gagtgatagg atatggcagt gacggcattt tcgggactga gtacaaaatt 128640
gccgtaggtg gccggcgccg agaccgtttc tttggtgatg tggcttgaga gcagcgacat 128700
gatgatctgc ataacgttgg ccgtgcttac catcacgccg ctgatcttgg cccccgagct 128760
cgtggtgtac gtggtggggt tgtctaggat gctatcggtg gccgcttcgg ccagacgcgt 128820
gaggaacttg agcacatagt cgcgatcgcg cgtgcgattc agcaaaaaga gcgtggccag 128880
cattttggcc ttgaagctct gcaagatgtt gcttcgctgg atgcggttca gtgcctgtcg 128940
cgccagtgtg gcgttttcta ccagcgtctg caccacaaag tacggcggcg ccttgcgtag 129000
cagtgtctgt aaaaagctgt gaatcaagcc gcgctccatg gcgtcggccg tgtttttaag 129060
cgcgcgcagc accgtgtgca tggcttccac gttgaggatc ttgtccaaga tggtgccctc 129120
gaatgtctcg cgcagatacg tgaggcaggc tgcgctgagc tcgaagggga tggtgatggg 129180
ggatttttca ctgtatttgg tgaccataat ggtggtctga cgactagtgg gcaaaccggc 129240
gccgctggcc acacgcggca cctgcacgtg gaacagcatt ttgcccgtag tcagtttatt 129300
gaggtcgtgg aacttgatgg cgtgcgccgc cgcggccaag ccgctggtca aaaaataaac 129360
ccattccagg cgattgcaga aggtgccgaa gatggcttcg aagtgaatat tgtaacgctc 129420
ggggtcatcg ccgtagtaga tgcgtaaggc ctcaaacatc tcctcgccgg cgctggtctt 129480
gacgtgcgtc agaaagtcag tgggaatgcc tactttaggc aggagctcga gcgccgacca 129540
gttctccatc gcggcggcgg cgtgagcgcg aggcgtcgga gctcggggaa agcagcgcga 129600
cccggagaat ggccggcgct gcgccgcgcc gcctcggctg tgacgctcta atagtcgttg 129660
gcggctccgc tatgccgcgc cgggttttac acgtccccgt gcacgttcgc gcctgcaacc 129720
tcacccaaga gctatcgacg ggcgaggacg cccgcttttg tcgtccgcga cccgttaacg 129780
tcgaacgggt gcgcgctgtt tttgcggctc tctaccgtgc ctgtccgata cacgtgagga 129840
ccgagcccga gcgtgtcaag ctggtactgg gtcgtctgtt actgggaccc gtggccgtac 129900
cctgtttttg cgacggtgaa gtggagggcc acggtgaaca tctggtacct acgacgcagt 129960
tttgtcgcgg gccgctgctc tacgtgcacc gacgttgttg ttgcggatcc gtgaccgccg 130020
ggcgcgcgct gtcctaccac gttctcgaaa accacgtggc cacgcatgtg ctacgcggat 130080
tgctctcgct gacggaatgg aatcgagaat tgccgagcct cttttgcgac tgtcctggcg 130140
gcggtggcgc ctcgggaacc gaggaacgct acgctatggc ctgcctgccg cgcgacctca 130200
gcctgcacct ggacgactat ccttacctga tggtggaaat cggacgcgta ctcagtgtca 130260
gcgaggtaga cgactacgta accgccgtct ccggctacct gggcgaggcc gcggcgccgc 130320
gcatccaggt tcactacaag ctgctctttg gactcaacgt gcgtccgcaa gcgccgtgcg 130380
cgttggacgc tacacgcgac ttttttctgc tggagctgca aaagctttgg ctgggcgttg 130440
aatatcacca cgaagtcacg tcggagtttt tcggtcgcgt actggctcag ctgcatcgcg 130500
accgcgcccg cgtcatgatg gcgcttcgct tgcccgagca gacggtgtgc cacctgagca 130560
ccttcgttct cagtcgcttc aagcgacagg tactgtactt caagctacag gtgagctacg 130620
gcaagtgccg gactggtcac gctgacagaa gtgggggagg ggggaacggt ggaaatcagg 130680
gacaccacaa cctactgtgt tatcgacgcc ttagcgtcac atttgccgac acagacacgg 130740
tgtggagaaa ccttttctac gtttattacg aactagctcg ggatctgggg tcccatggga 130800
cggaggaccg acccgtaagc cgcggttacg gtgtttcttg cgcttcgagg acgtcgcgac 130860
tgtcaccgtc agaatcgacg gtggtttcgg cgaacggaca cgcgctgtct tccaccgcgc 130920
tcccgacgac gagcgcgggt cacaagctgt cactgccgcg cgacccggcc gcagatcgcg 130980
ttcgacgtta cgtatgcatt atctcgcgtc tcatgtacgc tcggtacggg gagagatggc 131040
gtaaacactg tcaacggcgg tcggagacgg gagaagagga ggaggaagag acgctggaat 131100
cgggggagac tgacgccacg ccgccatttg actttacggg gcagcagctg cgccgggcct 131160
atcaggaaca ccgacgtcgt aaacatctag ccgtgcagcg ttacgcgccg tgccgtcgta 131220
agctcatcgg cgggatggag tttgccgagg tgacgggcgt gagtctagac cgcatcgccg 131280
tcaacgcttt caacaccaac cgcgttatca atatgaaggc tgcgctctcg tccatcgccg 131340
cgtcgggtct cggcgtacgc gcgccgcggc ttcccaagaa catgacccac agttttgtga 131400
tgtacaagca cacctttaag gagcccgctt gcaccgtcag cacttttgtt tccaacgacg 131460
ccgtctacat caactcgctc aacgtcaata ttcgcggttc ctaccccgag tttctgtact 131520
cgctgggcgt gtaccggctg cacgttaata tcgatcactt ttttctgccg gccgtggtgt 131580
gcaacagcaa ctcctcgctg gacgtgcatg ggctggagga ccaggcggtg attcgctcgg 131640
agcgcagcaa ggtgtactgg accaccaact ttccgtgcat gatctcgcat actaacaacg 131700
tcaacgtggg ctggttcaaa gcggctacgg ccattgtgcc gcgcgtctcg ggcgccgacc 131760
tggaagccat tctgctcaaa gaactctcgt gcatcaagaa catgcgcgac gtgtgcatcg 131820
attacggtct gcaccgtgtt ttcacgcaac tagagctgcg caattcgtac cagatcccct 131880
tcctggccaa gcagttagtg ctgtttctgc gtgcttgcct gctcaagctg cacggtcgag 131940
agaagcggct gcagttggac cgcctagtat ttgaggcggc acagcggggt ctctttgact 132000
acagcaagaa cctcacggcg cacaccaaga tcaagcacac ttgtgcgctc atcggcagtc 132060
gtctagccaa caacgtgccc aagatcctgg cccggaacaa aaaagtcaaa ttggatcacc 132120
tgggccggaa cgccaacgtg ctgacggtgt gtcggcacgt ggaagcccac aagatccctc 132180
gcacgcgcct caaagtgtta gtcgaggtgc tgggcgcgtt gcagagtatc agcggtacgc 132240
cgcacacgcg cgaagtgatc caccagacgt tgtttcgatt gtgctcggcg gccgcagcca 132300
catcgggcct gtgttcatcc cctcccccat tgtgtgtgtc ctcatcttcc tccgtccctt 132360
ctgtcccaac ctccgtcagc gttgacggca gttctgaacc cacgtcgccg cgagcgcggt 132420
ttgcatcacg atgatggaag ccgcggccgc tgccgccgcg gcgtttcgtc cggaggagcg 132480
tccgacgccg ggttggcacg acgcggcgtt gttaatggac gacggtacgg tgcgcgagca 132540
cgcgtttcgc aacggaccgc tgtcgcaact gattcgccgt gtgttaccgc cgccgcccga 132600
cgccgaagac gacgtggttt ttgcttccga gctgtgtttt tattgcagcg gtcgttttaa 132660
ccgcaggtcg tccgtcttct ccatctattg gcagaagcat agcgatctgg tgtacgcgct 132720
tacgggcatt acccattgcg ccaagttggt ggtggaatgc ggtcagttgg ggagtagtag 132780
gctacggtgg cgcgacggtg atgcgagtgg tgaggagcgc cggggagacg acgacagcag 132840
ggacgagctg tacgacgtgc cgggcattta tatgattcgc gtcaacgacg gcggcagcac 132900
cggccccaga cacgttattt ggccgggtac cagcgtgctt tgggcgccgg acgttgtgat 132960
cactacggtg cagcgacgaa tctcggcggc gcgcgccctg gtgaacacgt tccgccaata 133020
tttttttttg ctggaacggc gctcgcacga ggagctggtt ctttgtccgc ccgagatgga 133080
ggagcgtcta gcgccgctgt tgcagagtgc cacgcgcggt gattcggaca tgtttgacgg 133140
tgtggtggcc agcgcttatc accgtttgcg aatgagtaat attccgcgtt catccgcccg 133200
tctgctggaa cactgcgtgg ggctggcggg tgctaagaag ctgctcttgc tcgacgtgcc 133260
gcgtctggag aactattttc tttgtcaagt ctgtctttac gagctggacg aggacgagat 133320
gggcgaggag atgctgggca tgttggccgg aaagcccgag gatgccgccg tctcgggcgc 133380
aagcggcggt tttctgctac atcgcaagac gatgaagctg gccgcctgtc tgtgtttgtt 133440
gctcaattcg ctgcatttgc accaggaggc gctggaggcc ttggatcctc cgccgccgcg 133500
cgtcgaggag aacgaccttg tcaacgtggt gctgcgccgt tattatcgca gtcacggcgg 133560
cgtgcaggcg cggacgctgg cggcggcccg ggctttgtta gccgactacg ccgaaacgtt 133620
ttcgcccttg gggagtttta cgcgcctggg ttacgatcgt ctcgtttctg ccgatgccgg 133680
cgtcagtcgc cggcacctgg tggctctgct gcgtgcctag ctgaccctga aacggatggc 133740
gtgtatatcg tcacacaggt aggtggccat gatgacggcg atgataagat cgtccgagat 133800
acgattctgg cgcttggccg agtaacgcgc cgtcgtgcct tcggccagcg tgacgcggtg 133860
caggttctga atctgctcca gaagatactc gatggggtcg tggctcagct tgatggtgta 133920
ggagacgagc tcttgcgagg ctttgatgta gcccgagttg aaacgcgaga tgaactgttc 133980
cacggccagc gccttgtcgc ggcccatgag gtagaagggc tgttcgatgt ggttctggtc 134040
gggcgtgtgg tagaagagca cgcggatgag cgtgctgctc tgcacgctct gtcggatgag 134100
gcaggcgatg cgcacggccg ccgcctggtt ggtgttgccc tccacggcga tgcgcagttc 134160
gtccaggtaa gggtgcaggc tcagcaccga gatgatcatg tgcgccgcgc actcggcgat 134220
ggctacctca gaactctcgg agaggtcgcg caaaaagaaa tgctctaggc cgtaaatgag 134280
aaactggtgt cggtaggcgc ctacggccgc cacgcccgtg cccgaggcct tgcggttggt 134340
ggtgaaggcc gggtccagat acacgtaaag cgtcttgccg aaataatcgt aggcgttggt 134400
gttgagcgtg ctgtaacgca aaatatcgaa ctcttcgcgg ctctggtccg tgatgagcac 134460
ggtgttctgc gagattttat tggtaccgcc gatgatctcg tccatgaaag cgcccggcat 134520
aaacatgttg gccgtcttgc gcacttgcga gttgaggctg atgaaggtgg gcttgtgcag 134580
tcggtagcaa ggacacgccg tggcgtcgcc cttctccgtg aagctgtgca ggtgctcttc 134640
gcacacgtaa gagaccacgt tgagcatgtc aaagggcgca ttgttaaggc gcgtcaagaa 134700
acacgtggag tcactggtag tgttggtgga cgatatgaag atgatcttgg tggtattctg 134760
ggccaggaac cccagaatgg tgttgaaggc ctctttcttg atgaagtgcg cctcgtccac 134820
cagcagcaag tggaagtttt gtcctcggat gctctgtgta gagaggagac agaaaaggga 134880
ctcttatgat tacgcacgct cgactggaag cctacagagt cggggtgggg ccggacaggt 134940
gagccaggtg agccgccagg tgaggcggga tcgccgtgtg ccaaccgggc tgcgacctga 135000
aaaccggaac caatccgccg acaccggcgc cgcgtgacgc gcgcccataa aaacgaaagt 135060
gtcgtcgtcg cgacccgcca cagccgccat gaactcgttg ctggcggaac tcaaccgact 135120
aggggtcgcg cacgccacta cggaggatgt ttttatcttt gtcgaccgcc tctttcaaca 135180
cttttccttc cttttccagg ccgaggagtc aggcccgcgc cgcttggaac tggtcgcgtc 135240
cgtgttcgag cacctgacgg tggagtgcgt taacgacatc ctggacgcct gcagtcaccc 135300
ggacgtgaac gtcgcggaga caagcaacac ctgtcgtccc tgcccttctc ctgttccctc 135360
cgcccccaaa actgtcagcg gcgctcagac gtcatgtgcg acgcctcggg cgcctgtgac 135420
atgaggcacg tccagaacgc gtttaccgag gagatccagt tacactcgct ctacgcgtgc 135480
acgcgctgct ttcgcacgca cctgtgtgat ctgggcagcg gctgcgcgct cgtctccacg 135540
ctcgagggct ccgtctgcgt caagacgggc ctggtatacg aggctctcta tccggtggcg 135600
cgtagccacc tgttggaacc catcgaggag gccgcactgg acgacgtcaa catcatcagc 135660
gccgtgctca gcggcgtgta cagctacctc atgacgcacg ccggccgtta cgccgacgtg 135720
atccaggagg tggtcgagcg cgaccgcctc aaaaagcagg tggaggacag tatttacttc 135780
acctttaata aggttttccg ttctatgcat aacgtcaacc gtatttcggt gcccgtcatc 135840
agccaacttt ttattcagct tatcatcggt atctactcaa agcagaccaa gtacgacgcg 135900
tgtgtcatca aggttagtcg taagaagcgc gaggacgcgc ttctgaaaca gatgcgttcc 135960
gaatatggaa acgcacctgt attcggatct ggcgtttgaa gcgcggttcg ctgacgatga 136020
gcaattgcct ctacacttgg tgctcgacca ggaggtgttg agtaacgagg aggccgagac 136080
gctgcgctac gtctactatc gtaatgtaga cagcgctggc cgatccacgg gccgcgctcc 136140
aggcggagat gaggacgacg caccggcctc cgacgacgcc gaggacgccg tgggcggcga 136200
tcgcgctttt gaccgcgagc ggcggacttg gcagcgggcc tgttttcgtg tactaccgcg 136260
cccactggag ttgctcgatt acctacgtca aagcggtctc actgtgacgt tagagaaaga 136320
gcagcgcgtg cgcatgttct atgccgtctt cactacgttg ggtctgcgct gccccgataa 136380
tcggctctca ggcgcgcaga cgctacacct gagactggtc tggcccgacg gcagctatcg 136440
tgactgggag tttttagcgc gtgacctgtt acgagaagaa atggaagcga ataagcgcga 136500
ccggcagcac cagttggcca cgaccacgaa tcaccgtcgg cggggcggac tgcgtaataa 136560
cttagacaat gggtcggatc gccgtttgcc cgaagcggct gtggcttctc tggagacggc 136620
cgtcagtact ccattttttg aaattccgaa cggagcagga acctcctccg cgaacggcga 136680
cggcagattc agtaacctgg agcagcgggt agcgcgtttg ttgcgcggcg acgaggaatt 136740
catctatcac gcgggtccat tggagccgcc ttccaagata cgcggtcatg agttggtgca 136800
gctgcgcctg gacgtaaatc cagacctcat gtacgccacc gatccgcacg accgcgacga 136860
ggtcgcgcgt acggacgagt ggaagggtgc cggtgtctcg cgtcttcgcg aggtctggga 136920
tgtgcagcat cgcgtgcgcc tccgtgtgct gtggtacgtc aattcctttt ggcgcagtcg 136980
cgagctgagc tacgatgacc acgaagtcga actataccgg gcgttggacg cttatcgggc 137040
gcgcatcgcc gtcgagtacg tgctgattcg cgccgtgcgc gacgagatct acgctgtact 137100
acgacgggac ggcggcgcgt tgccacagcg tttcgcctgc cacgtgtcac ggaacatgtc 137160
ctggcgcgtt gtttgggaac tttgccgtca tgccttggcg ctctggatgg attgggcgga 137220
cgtgcgtagc tgtattatta aggcgctaac gcctcgtctg agccggggtg ccgccgctgc 137280
cgctcagcga gctcgtcgcc agcgcgagcg ctcggcgccc aaaccgcagg agctgctttt 137340
cgggccgcgg aacgagagcg gtccgcccgc cgaacagact tggtacgctg acgtggtgcg 137400
ctgcgttcgc gcgcaagtgg atttgggcgt ggaagtgcgc gcggcgcgtt gtcctcgcac 137460
cgggctttgg atcgtccgtg atcgccgcgg acgcctgcga cgttggctct cgcagcccga 137520
ggtgtgcgtg ctgtacgtca cgccagactt ggacttttac tgggtgctgc cgggcggctt 137580
tgccgtctct tcgcgcgtca ctcttcatgg cttggcgcag cgggctttgc gagaccgatt 137640
ccagaacttt gaagcagttc ttgcaagagg aatgcatgtg gaagctggtc ggcaagagcc 137700
ggaaacaccg cgagtatcgg gccgtcgctt gccgttcgac gatctttagt ccggaggacg 137760
acagctcgtg tatcttatgc cagttgctgt tgctctaccg cgacggcgaa tggatcatct 137820
gtttttgctg caacggccgt tatcaaggcc actatggcgt gaaccacgta catcggcgtc 137880
gtcgacgcat ctgtcatcta cctaccttgt accaactgag cttcggaggt cctttgggtc 137940
cagccagcat cgatttcttg ccaagcttta gccaggtgac cagcagtatg acgtgcgatg 138000
gtattacgcc cgacgtgatt tacgaggtct gcatgttggt gccccaggat gaagccaagc 138060
gtatcctggt caagggtcac ggtgccatgg acctgacctg tcagaaggca gtgacgctag 138120
gcggcgccgg cgcctggttg ctgccgcgtc ccgaaggcta cacgcttttc ttttacattc 138180
tgtgttacga cctgtttacc tcatgcggca atcggtgcga tatcccttcc atgacgcgcc 138240
tcatggcggc ggccacggcc tgcgggcagg cgggttgcag cttttgcacg gatcacgagg 138300
gacacgtaga tcccactggc aattacgtgg gttgcacccc cgatatgggc cgctgtcttt 138360
gttacgtgcc ctgtgggccc atgacgcagt cgctcatcca caacgaggaa cccgcgactt 138420
ttttctgtga gagcgatgac gccaagtacc tatgcgccgt aggttctaag accgcggcgc 138480
aggtcacact gggagacggc ctggattatc acatcggtgt taaggattct gagggccgat 138540
ggctgcccgt caagaccgat gtgtgggacc tggtcaaggt agaggaacct gtgtcacgta 138600
tgatagtgtg ttcctgtccg gtgcttaaga acctagtgca ctaacggggt ctgacagttc 138660
acggggagaa gaaacaagaa acaacaaaaa aaaggaggac atggactcgc cacggtttgt 138720
ggcaaggcgt atgttatcat catggagcta ctcacgttgg tgttgtagca actggcaaaa 138780
agcgccgtgc tcttggcgcc gcggtggtcg atgctgatca cgttgtcctt gttctcgacc 138840
acgtagtcgc gcgcgaaggt gtggcggcag cggaactcga cctctttgag cacaaactgc 138900
gacacgtgct tttggtgcgc cacgtagccg atgctgatgc cgatcatgtg cttaagcaga 138960
aacgagataa tggggatgat gaaccaagtc ttgccgtgac gtcgcggcac caggaacacg 139020
gtggctttct gcttaaagat gtcgatggag gtctgcgaga ggaagtcgat ctggaaggcg 139080
tggatgaggt actgcagcac gcgattggcc agcacgggga tcttggtcac ggctataaaa 139140
aagatgacgt gtatcaataa attcttttga aacggttcga gtcggatggc ttttgcgtcg 139200
ccctcgacgg cggtactgaa gccgccgtcg agccactttt taaagtcggt catgaagttg 139260
ttgatctgct gaaactgcgg atcgcggtag agctcggtca acgcgtccag cttctggtag 139320
gaggcgcgct gctcctcgga gcacgggcga aacgtcagtt tatcgagcgc gctcttgagg 139380
cgctcgtgaa acagcagctc gcgctggctt tcctcgggcg agttgtagtc gcggtggcgg 139440
ccgcagaagg ccatgagcgg caggaaggcc tcgttgcacg agtgggccag cccgagttcg 139500
gggtgcatca tctggtagcg cttgcggcac agcgtcgcca cattggtgaa ggccgtggag 139560
atgcaggagg tggggtggct cttgcgcttc tgcagctccg cgtagcgctc ctggatcttg 139620
gcggccgagt ctccgcgcaa catgatggcg gcggcggtgg tgcgagcgga ggttaggcgg 139680
cagcggcgag aggagaggaa aaagatggcg gccgcgagga cgacggagga tccacccgaa 139740
aaccacgttg ttgcggacgt ggctcgtggg acgggcgccg tcactcgttc gtcttcgtcg 139800
tccctagtgg tgtcgtcttc ctcggcgtca ggctcggacg aatcttcctc cgcctctcct 139860
ctcagtttcc ccgtctcctc cccctcaact gccgtcaggt ctccggggtc cgccggggtt 139920
tcaacgtccc tgtgctcggt ggaacggatg gtcgagctgt cggcgcagtc tccggccgcc 139980
gatttctcgg tctccgaggc ttggcgcttc gaggaggccg taaatatggc gctggtggcc 140040
tgcgaggccg tgtcacctta cgatcgcttt cgcctaattg aaacgcccga cgagaatttc 140100
ttgttggtca ccaacgtaat tccgcgcgaa tcggccgagg tgccggtgtt ggatagcagt 140160
agcagcggtg gcgatagcgg gccggaggac aaaaagaaaa acgtcgggaa taaaaccgcg 140220
ggggaaaaga acggcggtgg gtctcgggcc aaacgccgtc gtagacgacg cgctccgaaa 140280
aacgacgccg ccacgccgtc ttttctacgt cgacacgacg tgctggagcg tttcgcggcc 140340
gcggctaagc ctttgccgtc gctttgtgtg cgtgattatg cgttacgcaa tgctgaccgt 140400
gttacctacg acggcgaatt aatctacggc agttacctgt tgtatcgcaa ggctcacgtg 140460
gagctgtcac tctccagcaa caaggtgcaa cacgtggaag ccgtgctgcg acaggtgtac 140520
acgccgggct tgttagatca tcacaacgtg tgcgacgtgg aggccctgct gtggctgctg 140580
tactgtggac cgcgcagctt ttgcgcgcgt gacacttgtt tcggtcgcga aaagaacggt 140640
tgtcctttcc ccgcgttgtt gcccaaactc ttttacgaac ccgtgcggga ctatatgacc 140700
tacatgaatc tggctgagct gtacgtcttt gtttggtatc gcggctacga attccctgcg 140760
ccgacgccgc aggcgacgac ggcgggtggt ggtggtggta gtggtggcgg cggcggggcc 140820
ggcgcttgtg cggtcgagac gagcgcgtca gcaggccggg tcgatgacgc cggcgacgag 140880
gtgcatttgc ctttaaagcc cgtctcgctg gaccgtctca gagaggtgtt gcaggcggtg 140940
cgcggccgct tctcggggcg cgaggtgccc gcctggccgg cctcgtcgcg cacctgtttg 141000
ttgtgcgcgc tctacagtca gaaccgtctc tgtttagatc tcgcgcgtga cgaggcgcgg 141060
accgtgagtt atagccccat cgttatccaa gactgcgccg cggctgtcac cgacgtcact 141120
ttgagccaca tcttgcccgg ccagagcacc gtctcgcttt tccccgtcta ccacgtcggc 141180
aagttgctgg acgctctctc gctgaacgac gcgggtctca tcacgttgaa tctatgacgt 141240
cggtcaacaa acagctctta aaggacgtga tgcgcgtcga ccttgagcga cagcagcatc 141300
agtttctgcg gcgtacctac ggaccgcagc accggctcac cacgcagcag gctttgacgg 141360
tgatgcgtgt ggccgctcgg gaacagaccc gatacagtca gcgaacgacg cagtgcgtgg 141420
ccgcacacct gttggagcaa cgggcggccg tgcagcaaga gttgcaacgc gcccgacagc 141480
tgcaatccgg taacgtggac gacgcgctgg actctttaac cgagctgaag gacacggtag 141540
acgatgtgag agccaccttg gtggactcgg tttcggcgac gtgcgatttg gacctggagg 141600
tcgacgacgc cgtctaacag gtatagcaat ctccgtcacg cctctgttca gattttatta 141660
aaaaaaaaac acaacataac gacagtgtcg gtgtggtagc tagtgcagcc ttaggaacag 141720
ggaagactgt cgccactatg tcctccgcac ttcggtctcg ggctcgctcg gcctcgctcg 141780
gaacgacgac tcagggctgg gatccgccgc cattgcgtcg tcccagcagg gcgcgccggc 141840
gccagtggat gcgcgaagct gcgcaggccg ccgctcaagc cgcggtgcag gccgcgcagg 141900
ccgccgccgc tcaggtcgcc caggctcacg ttgatgaaaa cgaggtcgtg gatctgatgg 141960
ccgacgaggc cggcggcggc gtcaccactt tgaccaccct gagttccgtc agcacaacca 142020
ccgtgcttgg acacgcgact ttttccgcat gcgttcgaag tgacgtgatg cgtgacggag 142080
aaaaagagga cgcggcttcg gacaaggaga acctgcgtcg gcccgtagtg ccgtccacgt 142140
cgtctcgcgg cagcgccgcc agcggcgacg gttaccacgg cttgcgctgc cgcgaaactt 142200
cggccatgtg gtcgttcgag tacgatcgcg acggcgacgt gaccagcgta cgccgcgctc 142260
tcttcaccgg cggcagcgac ccctcggaca gcgtgagcgg cgtccgcggt ggacgcaaac 142320
gcccgttgcg tccgccgttg gtgtcgctgg cccgcacccc gctgtgccga cgtcgtgtgg 142380
gcggtgtgga cgcggtgctc gaagaaaacg acgtggagct gcgcgcggaa agtcaggaca 142440
gcgccgtggc atcgggcccg ggccgcattc cgcagccgct cagcggtagt tccggggagg 142500
aatccgccac ggcggtggag gccgactcca cgtcacacga cgacgtgcat tgcacctgtt 142560
ccaacgacca gatcatcacc acgtccatcc gcggccttac gtgcgacccg cgtatgttct 142620
tgcgccttac gcatcccgag ctctgcgagc tctctatctc ctacctgctg gtctacgtgc 142680
ccaaagagga cgatttttgc cacaagattt gttatgccgt ggacatgagc gacgagagct 142740
accgcctggg ccagggctcc ttcggcgagg tctggccgct cgatcgctat cgcgtggtca 142800
aggtggcgcg taagcacagc gagacggtgc tcacggtctg gatgtcgggc ctgatccgca 142860
cgcgcgccgc tggcgagcaa cagcagccgc cgtcgctggt gggcacgggc gtgcaccgcg 142920
gtctgctcac ggccacgggc tgctgtctgc tgcacaacgt cacggtacat cgacgtttcc 142980
acacagacat gtttcatcac gaccagtgga agctggcgtg catcgacagc taccgacgtg 143040
ccttttgcac gttggccgac gctatcaaat ttctcaatca ccagtgtcgt gtatgccact 143100
ttgacattac acccatgaac gtgctcatcg acgtgaaccc gcacaacccc agcgagatcg 143160
tgcgcgccgc gctgtgcgat tacagcctca gcgagcccta tccggattac aacgagcgct 143220
gtgtggccgt ctttcaggag acgggtacgg cgcgccgcat ccccaactgc tcgcaccgtc 143280
tgcgcgaatg ttaccaccct gctttccgac ccatgccgct gcagaagctg ctcatctgcg 143340
acccgcacgc gcgtttcccc gtagccggcc tacggcgtta ttgcatgtcg gagctgtcgg 143400
cgctgggtaa cgtgctgggc ttttgcctca tgcggctgtt ggaccggcgc ggtctggacg 143460
aggtgcgcat gggcacggag gcgttgctct ttaagcacgc cggcgcggcc tgccgcgcgt 143520
tggagaacgg taagctcacg cactgctccg acgcctgtct gctcattctg gcggcgcaaa 143580
tgagctacgg cgcctgtctc ctgggcgagc atggcgccgc gctggtgtcg cacacgctgc 143640
gctttgtgga ggccaagatg tcctcgtgtc gcgtacgcgc ctttcgccgc ttctaccacg 143700
aatgctcgca gaccatgctg cacgaatacg tcagaaagaa cgtggagcgt ctgttggcca 143760
cgagcgacgg gctgtattta tataacgcct ttcggcgcac caccagcata atctgcgagg 143820
aggaccttga cggtgactgc cgccaactgt tccccgagta accgggacgc ggaacgtgac 143880
ggttgctgag gggaaaggca acagagaagg tacaaaccca ccggcgggga aaataccgag 143940
gcgccgccat catcatgtgg ggcgtctcga gtttggacta cgacgacgat gaggagctca 144000
cccggctgct ggcggtttgg gacgatgagc ccctcagtct gtttctcatg aacacctttt 144060
tgctgcacca ggagggcttc cgtaatctgc cctttacggt gctgcgtctg tcttacgcct 144120
accgcatctt cgccaagatg ctgcgggccc acggtacgcc agtagccgag gactttatga 144180
cgcgcgtggc cgcgctggct cgcgacgagg gtctgcgcga cattttgggt cagcggcacg 144240
ccgccgaagc ttcgcgcgcc gagatcgccg aggccctgga gcgcgtggcc gagcggtgcg 144300
acgaccggca cggcggctcg gacgactacg tgtggctcag ccggttgctg gatttagcgc 144360
ccaactatcg gcaggtcgag ctcttccagt tgctggaaaa ggaatcgcgc ggacagtcgc 144420
gcaactcggt gtggcatctg ttgcgtatgg acacggtctc ggccaccaag ttctacgagg 144480
ccttcgtcag cggctgtctg ccgggcgccg cggcggcgga cggttcgggt ggcggcggct 144540
cgcactacac gggttcgcgc gccggcgtct cgccgggcat ccagttcggt atcaaacacg 144600
agggcttagt caaaacgctg gtggaatgtt acgtgatgca cggacgcgag ccggtgcgcg 144660
acggcctcgg tctgctcatc gaccccacgt cggggctgct gggcgcttcc atggacctgt 144720
gcttcggcgt gctcaagcag ggtagcggtc gcaccttgct ggtggaaccg tgtgcgcgcg 144780
tctacgagat caagtgccgc tacaaatatt tgcgcaaaaa ggaggacccc tttgtgcaga 144840
acgtgctgcg gaggcacgac gcggcggccg tggcctcgct gttgcagtca cacccggtgc 144900
cgggcgtgga gtttcgcggt gaacgcgaga ccccgtcggc acgcgagttt ctgctttcgc 144960
acgacgcggc gctcttcagg gccacgctca agcgcgcgcg cccgctcaag ccgcccgaac 145020
cgctgcgcga gtacctggcc gatctgctgt atctcaataa ggccgagtgt tcggaagtga 145080
tcgtgtttga cgccaagcac ctgagtgacg acaacagcga cggggacgcc acgatcacta 145140
ttaacgcgag tctcggccta gccgcgggcg acggcgctgg cggcggcgct gatcaccacc 145200
tgcggggcag cccgggcgat tcgccgccgc cgataccttt cgaggacgaa aacacgcccg 145260
agctgctggg ccggctcaac gtgtacgagg tagcgcgctt ttcactgccg gcttttgtca 145320
atccgcgtca ccagtattac tttcagatgc tcattcagca gtacgtgctc agccaatact 145380
atataaagaa gcatccggac ccggagcgga tcgatttccg cgacctgcct accgtctacc 145440
tggtctcggc catcttccgc gagcgcgagg aaagcgaact gggctgcgag ttgctggccg 145500
gcggtcgcgt tttccactgc gaccacatcc cgctcctgct catcgtcacg cccgtggtct 145560
ttgaccctca gtttacgcgc catgccgtct ctaccgtgct agaccgttgg agtcgcgacc 145620
tgtcccgcaa gacgaaccta ccgatatggg tgccgaactc tgcaaacgaa tatgttgtga 145680
gttcggtacc acgcccggtg agcccctgaa agatgctctg ggtcgccagg tgtctctacg 145740
ctcctacgac aacatccctc cgacttcctc ctcggacgaa ggggaggacg atgacgacgg 145800
ggaggatgac gataacgagg agcggcaaca gaagctgcgg ctctgcggta gtggctgcgg 145860
gggaaacgac agtagtagcg gcagccaccg cgaggccacc cacgacggct ccaagaaaaa 145920
cgcggtgcgc tcgacgtttc gcgaggacaa ggctccgaaa ccgagcaagc agtcaaaaaa 145980
gaaaaagaaa ccctcaaaac atcaccacca tcagcaaagc tccattatgc aggagacgga 146040
cgacctagac gaagaggaca cctcaattta cctgtccccg cccccggtcc cccccgtcca 146100
ggtggtggct aagcgactgc cgcggcccga cacacccagg actccgcgcc aaaagaagat 146160
ttcacaacgt ccacccaccc ccgggacaaa aaagcccgcc gcctccttgc ccttttaact 146220
cataaacttt caggtctcgc gtacgattcg cgagtcggga atgggacacc cgtgggtgtt 146280
tctccgtgtg tatattattt tttttttttg tgtgtgtttg cgcccccgtg tgtctaatgt 146340
gctgtttgaa acacgtaaag tagctggtgg aagaacagat aaacctttaa taaaaaaaaa 146400
agtatgtgct cccgacccac ggtctgcgtg tctctttttt atgtccatgt ctccaagtct 146460
ggtgcgggtg gcggcggggt taagcgtcct cgaagtcttc atcatcgtcg tcgtcctctt 146520
cttcgcggag gcgacggctt tccaagctgt cgtggtgact gagcacagcg acttcttcgc 146580
cggaggctgt ggccagcgcc tggtacttga cactgccgct accgcgtccg cgaaagtagc 146640
ggacggcgcg acacgtcgta aacatggccc atatgaaaaa gagcatgccg aacgaccagc 146700
tgatgccggt gcggtattcg ttgctgagga aggtatcgta ctgcacgatg gggtagatga 146760
ggccgcagag tccaaagaag gcgcccaggt ggtagccgaa ttgcaccttg acgtattgaa 146820
aaaagacggc ctcgatcagt aaaaagtaga tgatggagat gatagcgtag accacgaaga 146880
cggctaacac catgtggcct gtacgcacga aaaagttgtt tccgaagccg tagcacaggg 146940
ccatggctac cacggtggtg ttgaaaccaa gcgctacctc taccaggttg acgatgagcg 147000
tgcggaactg caccgtacct ttgagcttgg ggtgcagacg cgagaagaaa aagagtgagc 147060
gtttgtagct gcggtactgc gtgaccatgc tcacgttgaa aatggtcagg cagaaaaagt 147120
gcacggcggc catgaaggcg atcatgctgg gcagccgaaa tgacatggtc agtgtgaata 147180
gttggaacgt gtccatgctg agaatgaaga ggaaggctgt gaggctgtcg cccatgtacg 147240
aaatgtcgcg tgtcgactgg tttaggctca tgcctttgtc cttgcgcatg ctgatcttga 147300
tccagcatac caggtagtag atggtcacgg ctaaaaagac gagctgcatg aacacggcgt 147360
agcacaccaa ctgcaccgag tctaagaaaa gcataggcgt gtgcaggtgc attacgttgt 147420
aggccgacat gttgagcctt tcaaagtcca cgacgtgata gtagacgcag gggtagccca 147480
ggtgcggaaa attgctcagc actagatgca cgctgacgtt gacaaaagtc agcaccatga 147540
aaacgataga agcgctccat gtccgtgtat tcaccttatc cacgtgcgag ggggccatgg 147600
cgatagcggc ggcccgctcg ctcgggaggc gatgggggcg cgccgatgac gacaggctcg 147660
cgggtcgtta aatactacga tgggagccgc cgcggctcac gacgcggttt gagcacgtcc 147720
gggcggtcgg tgaaaaaaga ccccgcgggc cttcgcgact ctcttctgtc cgaggatgac 147780
cgctcagccg ccgctgcacc accgccacca cccgtacacc ctgttcggga ccagctgtca 147840
tctcagctgg tacggccttc tagaggcctc ggtgcctatc gtacaatgtc tgtttttgga 147900
tctgggtggc ggccgtgccg agccgcggct tcacacgttc gtggtgcgcg gtgaccgtct 147960
accgccggct gaggtgcgtg ctgtgcatcg cgccagctac gctgcgctgg cctcggccgt 148020
gactacggac gccgatgagc gtcggcgcgg cctagagcag cgtagcgccg tgttggcgcg 148080
cgtgttgcta gaaggcagcg cgttaatccg cgtgttggcg cgcaccttca cgccggtgca 148140
gattcagacg gacgctagtg gcgtggagat tttggaggcc gcaccggcac tgggcgtgga 148200
aaccgcagcg ctgtcgaacg cgcttagtct tttccacgta gccaagctag tggtcatcgg 148260
ctcgtatccc gaagtgcacg agccgcgtgt ggtcacgcat accgcggaac gcgtctccga 148320
agagtatggc acccacgcgc acaaaaaatt gcgtcgcggt tactacgcct acgatttggc 148380
catgtcgttt cgcgtcggca ctcacaagta tgtgctggag cgcgacgacg aggccgtcct 148440
ggcacgcctc tttgaggtgc gcgaggtgtg ttttttgcgc acctgtctgc gtctggtcac 148500
gcctgtcggt ttcgtggccg tggcagtgac cgacgagcag tgttgtttat tgctgcagtc 148560
ggcctggact cacctttacg acgtgctttt ccgtggtttc gctgggcagc cgccgctacg 148620
cgactacctg gggccggacc tctttgagac gggcgccgcc cgttctttct tttttcccgg 148680
tttcccgccc gtgcccgtct acgcggtcca cggtctgcac acgttaatgc gcgagacggc 148740
gttggacgcg gcggctgagg tgctctcgtg gtgcggcctg cccgacatcg tgggctcggc 148800
cggcaagctg gaggtggaac cctgcgcgct ctcgctcggc gtgcccgagg atgagtggca 148860
ggtcttcggt accgaggccg gcggcggcgc cgtgcgtctc aatgccacgg cttttcgcga 148920
gcgaccggcc ggcggcgatc gtcgctggct gttgccgccg ctgccacgtg acgacggcga 148980
cggtgaaaac aacgtcgtgg aagtcagcag cagcaccggc ggtgcgcacc cgccgagcga 149040
cgacgccact ttcaccgtgc acgttcgcga cgccacgcta catcgagtgc tcatcgtgga 149100
tttggtcgag cgcgtgctgg ccaagtgtgt acgcgcgcgc gacttcaatc cctacgtgcg 149160
ttatagtcat cgactccaca cttatgcggt ttgtgaaaag tttattgaga atctgcgttt 149220
tcgctcgcga cgcgctttct ggcagatcca gagtctgctg ggctacatct ccgagcacgt 149280
tacgtcagcc tgcgcttcgg ccggcctttt gtgggttctg tcgcgcggcc accgcgagtt 149340
ttatgtctac gacggctatt cgggtcacgg acccgtctcg gccgaagtgt gcgtgcggac 149400
tgtggtcgac tgttattggc gcaaactttt tggcggcgac gatccgggtc ccacctgtcg 149460
tgttcaagag agcgcgcccg gcgtgctgtt ggtctggggc gacgagcggt tggtgggtcc 149520
cttcaacttc ttctacggca acggcggcgc cggtggtagt ccgctccacg gggtggtggg 149580
tggtttcgcg gcgggacatt gcggtggcgc ttgttgcgcg ggctgcgtcg tcactcaccg 149640
ccattctagc ggcggcggtg gtagtggcgt gggcgacgcg gaccacgcga gtggcggcgg 149700
tctagatgcc gctgccggga gtggtcataa cggcggtagt gatcgggttt ctccctccac 149760
gccgcccgcg gcgttaggtg gctgttgctg cgcagccggt ggcgactggc tctcggccgt 149820
gggtcatgtc ctgggccggc tgccggcgct gttacgggag cgcgtgagcg tgtccgagct 149880
ggaagccgtg taccgcgaga tcctctttcg tttcgtggct cgccgcaacg acgtggactt 149940
ttggttactg cgcttccagc ccggtgaaaa cgaagtaagg ccgcacgctg gggtgattga 150000
ctgcgcgccc ttccacggcg tgtgggccga gcagggccag atcatcgtac agtcacgcga 150060
tacggcgttg gcggccgata tcggctacgg cgtctatgtg gacaaggcct ttgccatgct 150120
cacggcttgc gtggaggtct gggcgcgaga gttattgtcg tcctccaccg cttccaccac 150180
cgcttgttct tcttcttccg ttctctcctc cgccttgccg tccgtcactt cgtcctcttc 150240
gggcacggcg acggtgtctc ctccgtcttg ttcttcttcg tcggcgactt ggctcgagga 150300
gcgcgacgag tgggtgcgct cgctggcggt tgacgcgcaa cacgctgcta agcgggtggc 150360
ttccgagggc ctgcggtttt tccggctcaa cgcttaacga gtcacgtagg ggaactacgt 150420
gggtaagtga cgtggatact agtaaaaaaa gtgcgtcaaa gctcttagcg tgtgacgtgg 150480
atactagtaa aagggacgtc aaagctcact acgtgttgcg tgtttttttt ttttctatga 150540
tatgcgtgtc tagttcgctt ctcactcttc ctctcctcgt tcccagcgcg gcggcagctt 150600
ggggggtgag ggcaaattgg ggtagttggc gttgagcacg tctagcaggc ccaggcccac 150660
gggccaaccg tccacggtct tgcgctcggt cagcttgagg ctgaacgagt gtgcctcgtc 150720
ctgaccggta aggcggaaaa agaagcgtgc taccagctgc aggcaggtat gccgcgtctg 150780
ctggaagagc acgaaggtag cgggcacgta ctgcacaatg tgcggctctt tttcctcaaa 150840
gagcaggtag agcgcgctgc agatcagccg cctggcgctg tggtgcagca gccggccgaa 150900
gctttcgcgc acgttcaccg cgtccaggta ctggagcagg tcgtgcaggc acttgcgcgt 150960
taagttgcaa ttttccacgc acgaaataac ggtacagagc gcgaagtgca gcaggttgtc 151020
ggctttgacg atgccgcagc ggtgtttgag ccgcagatcc gagagcctca cctgcgtgac 151080
ggcgtcttcg gtctcgagca aaaacacggc ggagtagcct agaaaggccg aggtgcacag 151140
caactcgctg cggtactcgg ccatggagac cagcagcccg tgctccgtgt gcagccacag 151200
cttgtcgccg cgcaccgtaa agtcgagcac ttgcggctcc atgatcatca cattctgtct 151260
agtgaaatcc gtatggacct ccagcacgcc gcggatcatc agggcctcca tttcgaaatc 151320
ggccgacacg ctctgggccg cgccgctcct cgtctgccgt gatcaagcgg cgcggcgcgg 151380
acctttcaag tgttcctggg ccgccgctcg aggcagttcc cctttctggc actccgcccg 151440
ccgcttcgcg gctcatttgg cgccgacgcg ccttctcgcg gctgcaaatc agctccacgt 151500
atcggcaaaa cttgctgtcg tcgtaggcgg cggccacgat ctcgccgaag gagagctgca 151560
ggtaggcctc gggtacgggg tccagcgtgc ccagcgccag gatgtgacac agatagggca 151620
gggtcacgcg ctctaccgtg taattggagt agacgatggc ctcttcggcc ccttgatgcg 151680
tgaccagacg ccgtaggcga aaggtacgga aatactcgtt ttcccacaac tgcgtgagga 151740
agcgttccag cgactcggtg ccgggcacga actgcgagaa gaagctgttg gccaccaggc 151800
ggttgtcttc caccgccagc ggacggaagg gcgccgcgtc gcgcgccttg cgcacggcct 151860
ccaacacggg caggtggtag agttcggcgt cgcgcgcgcc caggctcatg gagtcctcgc 151920
gccgcgaggc gtagcgcgtg agcaggtcgc gcagttcgcg cacgcgattc tcccaggtct 151980
ggttaagcgt gcgcaggtcc tggatctcgt ccacctgcga ctggatctgc tcctccaggc 152040
acttgataac ctgcttctta aacaggtcgc ggatgtcccg ctcgggcgcc gccgggccgg 152100
gtggcggcgg cagcagcccg acgtggcccg cgggtcctcc caccacggcg ccgccgggtc 152160
ccaccacgcc gggtccgccc ggaccacgcg cgggtagtag acggttttgg tccaccagcg 152220
agggggtcag gtcctgcaga aaggactcga cgctgtcctc gatgccgatg cgcgatttgc 152280
tgtccgagac gttaagcaaa aacttcataa tggacttttt ggcgtcgctg ccccggtcgt 152340
gctgctccat catctccacc agcttcttgc agttgagctc gtggcggctg gcggtcacca 152400
ctttcacagg aaaggtattg agcaactggc agatcttttg gtggcggcag agcccgtcgt 152460
agcgcagaat ctcctcgtgc aggtgtgcca ccggcgtggt gaacagcagc ttgtcgcgct 152520
cataagccag cggttcggcc gccacgtaca agcggatgtg cttgccgcgc agctgcgcct 152580
ccagccgctc cgagcgcacc ttcttgaaga cgcgtacctc gggcgcgttg gctacgcgca 152640
cggcgcccag gcgctcggcc acctgcagca gcagcgccag gttagcctgc agcaggtcct 152700
gcgccagcgg gtgtgtctcg gtggcccgct gcacggccgc gcgtacaaat tgcgcccgct 152760
cggccgcctc gctcggcttg gtcttcacgt ccagcagcgg taccagtccc accgttacgc 152820
accaatccac gtagagacca tagtcgtcgt tatcggcgta ctgatataaa atgtcgcgga 152880
gcgcgcccag cacgcccgtt tgcacgctct ggcgcaacga ggcgctccac accaacagat 152940
actgctccag gtcctcttcg tccagcgcgc ggtagggaaa tagcgccgcg tgcaacttcc 153000
actcctcggc cacgcgccgc accgtgatgg tgtcaaagag cgttttgcac actccgtaga 153060
gcagctgctt gcgcagcacg cacgggtcgc gcagcacctg gtgcatgctt tggccgcgac 153120
acgtccccag aaagccgtgc agcaaccgca ggaagctcat cgtctgcccc gtggggaaaa 153180
tgtcgatgac ggcctcgtca tccacgccgc ggcccacgcc caagtacgac gacgccttga 153240
tcctcaacct ctcgtcggcc gccaagatcg aacggatcgt cgacaaggtc aagtccctct 153300
cgcgcgagcg ctttgcgccc gaggattttt cgttccagtg gtttcgctcc atcagtcgcg 153360
ttgaacgaac gacagataac aacccctctg ccgcaactac cgccgcggca acgacgaccg 153420
ttcactcctc cgcctcctct tctgccgccg ctgccgcttc gtccgaggcc ggcggcacgc 153480
gcgtgccctg cgtcgaccgt tggcccttct ttcccttccg cgcgctgctc gtcaccggca 153540
cggcgggcgc cggcaagact tccagcatcc aggtgctggc ggccaatcta gattgcgtga 153600
tcaccggtac cacggtgatc gccgcgcaga acctcagcgc gatcctcaac cgcactcgct 153660
cggcgcaggt caagaccatc taccgcgtct tcggcttcgt cagcaagcac gtgccgctgg 153720
ctgacagcgc cgttagccac gagacgctgg aacgctaccg cgtgtgcgag ccgcacgagg 153780
agaccaccat ccagcgcctg cagatcaacg atctgctcgc ctactggccg gtcatcgccg 153840
acatcgtgga caaatgctta aatatgtggg agcgcaaggc cgcttcggcc tccgccgcgg 153900
ccgcagccgc cgcctgcgag gacctctcgg agctgtgcga gagcaatatc atcgtcatcg 153960
acgagtgcgg ccttatgctg cgctacatgc tgcaggtggt ggtgtttttt tactactttt 154020
acaacgccct gggcgacacg cgactttacc gcgaacgccg cgtgccctgc atcatctgcg 154080
tcggttcgcc cacgcagacc gaggcgctgg agagccgcta cgaccactac acgcaaaaca 154140
agagcgtgcg caagggcgtt gacgtgctct cggcgctgat tcagaacgag gtgctcatca 154200
actactgcga catcgccgac aactgggtca tgtttattca caacaagcgt tgcaccgacc 154260
tggactttgg cgacctgctc aagtacatgg agttcggtat cccgctcaag gaggagcacg 154320
tggcctacgt ggatcgcttc gtgcggccgc ccagctccat ccgcaacccc tcgtacgccg 154380
ccgagatgac gcggcttttt ctctcacacg tcgaggtgca ggcttacttc aagcggctgc 154440
acgagcagat ccgcctgagc gagcgccacc gtctctttga tctgcccgtc tactgcgtgg 154500
tcaacaaccg cgcgtaccag gagctctgcg agctggccga cccgctgggc gactcgccgc 154560
agcccgtcga gctctggttc cgccagaact tggcgcgcat cattaactac tcgcagtttg 154620
tcgaccacaa cctctccagc gagatcacca aggaggcgct gcgccccgcg gccgacgtcg 154680
ttgccaccaa caactcctcc gtccaggctc acggaggggg aggatctgta atcgggagca 154740
ccggcggcaa cgacgagacg gcgtttttcc aggacgatga taccaccact gcgcccgata 154800
gccgtgagac gctgctcacc ttgcgcatta cctacatcaa gggcagttcg gtgggagtca 154860
actctaaggt gcgggcctgt gttatcggat accagggcac ggtcgaacgt ttcgtggaca 154920
tcttgcaaaa ggacacgttt atcgaacgca cgccctgcga gcaggcggcc tacgcctact 154980
cgttagtttc gggcctgctc ttctcggcca tgtactactt ctacgtgtcg ccctacacga 155040
ccgaggagat gttgcgtgag ctggcgcgcg ttgagctgcc cgacgtgagt tcgctctgcg 155100
ccgctgccgc cgccacggcc gccgctcccg cttggagcgg gggagagaat ccgataaata 155160
atcacgtcga cgcggattct tctcagggcg gccagagcgt gccggtatct caacggatgg 155220
aacatggcca agaggagacc cacgacatcc cctgcctgtc caaccaccat gacgactcgg 155280
acgccatcac ggacgccgaa ctcatggatc acaccagtct gtacgcggat cccttttttc 155340
tcaaatacgt caagccacct agcctggcgc tgctttcttt cgaggagacg gtgcacatgt 155400
acactacctt ccgcgacatt tttctcaagc gctaccagct catgcagcgt ctcacgggcg 155460
gtcgcttcgc cacgttgccg ctcgttacct acaatcgccg taacgtggtg ttcaaggcca 155520
actgtcagat cagctcgcag accggctcct tcgtgggcat gctttcgcat gtgtcgccgg 155580
cgcagacgta cacgctcgag ggctacacca gcgacaacgt gctcagtctg cccagtgacc 155640
gccaccgcat ccaccccgag gtggtgcagc gcggcctttc gcggctggtg ctacgcgatg 155700
cgcttgggtt cctctttgtg ctcgacgtta acgtttcgcg cttcgtcgag tcggcgcagg 155760
gcaagagtct gcacgtgtgc accaccgtgg actacggcct cacttcgcgc acggccatga 155820
ccatcgccaa gagtcagggc ctgtcgctcg agaaggtggc cgtggacttt ggggaccatc 155880
ccaagaacct caagatgagc cacatctacg tggccatgtc gcgagtcacg gaccccgaac 155940
acctcatgat gaacgttaac ccgttgcgac tgccctatga gaagaacacc gctatcaccc 156000
cctatatctg tcgcgcgctc aaagacaaac gcaccacgct tattttttga cacaacaccg 156060
tgtaaggaaa acgtgacttt attgagcagg gtaaaaacca cgtacaagaa ccacgttgtc 156120
tatccccaaa aaaacacaca ccgtcaggga acacatcgcc tatagatagc ggcactttac 156180
ataaaaccac cgtacctgca tcacggtggc tcgatacact ggaaattcaa taaaaaccac 156240
cgtgtctccg tgacggtact tatcgggtca gcgtcttttg agatttctgt tcgtaaactt 156300
atccgtttcc ccggtccgcg gtgtctcctc gcgaggctga cagtcgacgg gtggtacctg 156360
caagagaaga aacccgggtg ggagcgacgc cgtcgctggg tatcaacccc gcggctgacc 156420
gtcgtccggt aaaggaacaa cccgtcgtcg caagccgggt tcgaccaaga gaaaaaaccc 156480
gggtgcgggg ggagacgggt cgtcctttgg ttgttcgcgg acggcgtaca tgccgcgtgg 156540
gtcagtcgac ggcgtcgctc cgtgcggtcg gtcatcattc tgcttcacat atatgggttg 156600
tttgtgtttt tttttataat gaatacgcac tgatcctatc cgtgactgcg cgtgtggcag 156660
agaggatgcc ttataacatg tattttgaaa aattgccaac agctataatt tctctcatgt 156720
agcagaatag agaccttttg tcgtcttttt gtttgtcatt acttgttttc cagggaatta 156780
gagagaggga accgcgcctc cggcggcggt gcccgcggac cccggcccct tctcgcgtgc 156840
gcggtgtgac tggttgagcg aatgagcagc taggcttggt ggtgctccgc gtgcggggga 156900
gaagacgatt aacaacaaaa aataagtgga agtggccggt gggtctttgt ccgcgtgcgc 156960
gcccatccgt cgccgggacc gagcagaaag tgatgtggtg gtacattgat tttttccttg 157020
acaggaaaga aaaaaaagag ttttgttttc ctatgtgaga ggagaaaggt atgtgaggag 157080
atgttcgatg atcgtatgtt acagttatgc tgtaaggaag cttttatcgt gcgtcctgtt 157140
tttcatttga tgtatatgac acaattgaaa cctatcgata ggcgtatatc gaggattcat 157200
caattcttag aatcgtcgtc tttttggcta attggacttt gcccatgttg gttgtcattc 157260
gtggcctgag gtcatcgtcg tccacgacga cgtgtctata gcgtgcggtg tgatcattgt 157320
gtcgagccag agaaagcgcg cctcgcacga cgtttgcgga tcggctcgcg ggtgtgtgga 157380
attcctaaga acataatcag ctggtcgtct ttctttgatg tgttgttgtc gtcgaggtct 157440
tgcttcgttt tcttttttct ttttagtcga tggaactttt cttcggtacg ggttcttgtt 157500
atggaagctt gtgttttcga acatgaattc gaaaaaataa aaaggcctat cttcgtttca 157560
aaaaaaggac agatatcaat cttcttaact tatatcatgg taaattcaga atcctatggt 157620
gtcttattat ctctaaagta gtcaacatta tggtctaact tgtatttccc tgacgagata 157680
tatatgatcc ttataacctg gctactatca tgaacaacaa tatccttact tacagtcatc 157740
ttcgtgagtt aatgaagtat aatatcggtc atctatcaac ttatctgcta tgtaacgtac 157800
ccttttaggt attttgcgtt tcttaacgag tgtacccgcc tgtgtgaggc gaaactctga 157860
gaagtctacc gagtcgagtt acaagtcact aaaacactta cacgagttat ctatactaaa 157920
atcactatct atgttgtttg cttacctaat tattatccta catgacgaag ctacctccca 157980
acgtaaggta gggggagagg agacagaaca ataaaaagta actaatgttt cttagaactt 158040
acccgctaag gacttaccaa actatattca ccaaaaaaca acagctacgt gtttcatttg 158100
ttttaatcta ccgaagtaaa aaaaaaaaga tgattagcta tccagaacct acttacttct 158160
taatgtttta actaaggatg cctatgggat tggaaaaaaa atcacagcaa cttgctacta 158220
atcagttgac agcgaagaga ctcataacaa agatttctgg gtaatacggt tataataatg 158280
cttatggact aaaggatact tggaaaaaaa gaacgggcta tgactataga gattcgtcga 158340
gatatcaaac ttcaaatagg cggctatcat tcatggttgt ggtgactata tcgtggagaa 158400
aaaatgtgat cgttagttag ctaggtgaga cttacagcta tccatccgtc tagtttttcg 158460
ttgtaatgat gatagtacgt ctatggtggt gatcgatttt ggttaacaat ttgttcgttt 158520
aaaggcttaa tgtacttatg ctacatgatg tattattctt tgattcatcg ttcctcctaa 158580
gggggtgtat gtatgtatgt actagtcgta tagtgttcct aacatcatga ctattcagac 158640
tatggcttca tctatcgtgt ctaaagttca cttattctac tattactata tatatgcact 158700
actatgtaac taggatatgg tcctataagg tgtcttctat cacggtggct tgtttatcgc 158760
ttggcggtta cgagcaagag ttcatcacgg accagccgtg aggcagggca cacgcgggtc 158820
ggcggcgatg atgtcccccg cgaaggggac aacgaaaaca agaggccgcc ggccgcggcc 158880
acggatgcgt agcggttaca caatgtttgg ttgagcgttt tgtttcatcg tcgtggtggt 158940
tttgttgttc tctgtatata tcgtgtggtg gctttatcgt catcattatt atcatcattc 159000
ttgtttccat catcacgatg agttttctcc gttttcctct cctccagtgg tagtcgtgta 159060
tcatcatcaa tcatcgtagt gacgtcgttg ctgctgctgc tcttgccttc atggcggtat 159120
ttctcttcct cccccctaac cccatattaa ctcgtgagtg tgatggttag agtggctgct 159180
tgtttttttt ttcttttctc tttggaacaa caaaagagga taaagatggt cggtgaatgt 159240
attattatta tcatcattat gatacggtcg cggtcttctt ctccgatgac gaaacctgcg 159300
cacatcgaag aaaagacgag cgcgcgaacc gatagccgtc cgtctgggac gaaggagaag 159360
atgatgggga gaggaggaga gccccagaag ccagagcgag aagggagacg acagacatac 159420
gtcgtcaccg tcctctggag gaggcacggc ggcgctgttt gttgtttgga tgcttgatta 159480
tatcctgttc tatggggtag attattatca ataggcttgg ttttcaaagg tcagcctgtg 159540
tattgtcgtg tctttttttt tcgttctcat gatcgcggag accacacaga cgtgcgcgtc 159600
tcccaatggc taggcgttct ttttaggtag taattttttg atcttttttt tttcttaaca 159660
agtctggctt gatttctttt atctatgatc gattcttctt tttctcgggg gttgcatctt 159720
ccgtgaaagt aaagtgacac tactctaaat ggtaaccata ttatctgttg attaggagaa 159780
aaaataattt tttcgcacga aatcgatcct aagtgaggtg atttacttgc tatcacacga 159840
aatgattatc ttttgctgct aacgtactga attttttaac agaattgctt ctccgtaact 159900
atttccgcag attcagacag attgtcaaaa aagaatacgg cacagaaata gtgggtctgt 159960
ggcttttggt tcgtgtacat tcgcgtttgc gtgtcgagat ttctacggta tgtttattct 160020
tcctgcgatg atgtagggtc cttggtgtaa gtaggatttc gagtatctct cttagagcga 160080
acaaaataat caaaaaacaa cagctaggaa atcgagggtt actctacgat aaagtgtctc 160140
tacaaagtga agaatgttac gttgtggtgg aataataaga ctcgcgtgat cgatgagtga 160200
tcgagagcgg ctcgaacctt ctttaagagc tttgtttagt gcaactttaa attacaagga 160260
gtagaaagct gaaatgaatc tatgaaggtg ctattctttg aatatcttac tttgtacgct 160320
tcacattcgt tatttggata gagagttgtc tagagaaaat ctgtgattct ctatgagtgt 160380
tatttttatt atccttttgg ggactacgat ttttcttctt gttctacata ccactactac 160440
tcgtaatcac atacatggac gaaaaaaaaa ttcgtcaggc agtagatacc agattctccg 160500
acgttacggc gtcttttttt tcttttgaga gagtatctgc tgagattgtc cgtggtgtat 160560
ctagtcgcta tttttgttgt tactagtagt tttgcacaca gtttattcag tatagttttt 160620
cttcttgcca tgatcaatta agcccaccac cttttttttt agagaggagg aatttcgtct 160680
tgatctccag ccggagacaa cggcggtggt ggtggtggcg ggagagactt caaggcaatg 160740
aaaaaaaaaa tttcgttttg ccatcaagtg gtgacgataa cccgtcagat tgataattgg 160800
ttcctacaga aactattcta accgcggaag aaagaaattg aaaaaaaaaa ttgacaaaaa 160860
catcataaca taaaggacca cctacctggg acgcgcagtt gggcggcgga ctgggacggc 160920
atgctgcggc gatgctgtcg gtgatggtct cttcctctct ggtcctgatc gtcttttttc 160980
taggcgcttc cgaggaggcg aagccggcga cgacgacgat aaagaataca aagccgcagt 161040
gtcgtccaga ggattacgcg accagattgc aagatctccg cgtcaccttt catcgagtaa 161100
aacctacgtt ggtaggtcac gtaggtacgg tttattgcga cggtctttct tttccgcgtg 161160
tcgggtgacg tagttttcct cttgtagcaa cgtgaggacg actactccgt gtggctcgac 161220
ggtacggtgg tcaaaggctg ttggggatgc agcgtcatgg actggttgtt gaggcggtat 161280
ctggagatcg tgtttcccgc aggcgaccac gtctatcccg gactcaagac ggaattgcat 161340
agtatgcgct cgacgctaga atccatctac aaagacatgc ggcaatgtgt aagtgtctct 161400
gtggcggcgc tgtccgcaca gaggtaacaa cgtgttcata gcacgctgtt ttacttttgt 161460
cgggctccca gcctctgtta ggttgcggag ataagtccgt gattagtcgg ctgtctcagg 161520
aggcggaaag gaaatcggat aacggcacgc ggaaaggtct cagcgagttg gacacgttgt 161580
ttagccgtct cgaagagtat ctgcactcga gaaagtagcg ttgcgatttg cagtccgctc 161640
cggtgtcgtt cacccagtta ctttaataaa cgtactgttt aaccacgttg cgtcgtgacg 161700
ttgtttgtgg gtgttgctag gcgggctgga aagatgatgt ataaatagag tctgcgacgg 161760
ggttcggcgc tctgccggct gcggcggcac tcgctccacg gcctccgacg agcgttgcgc 161820
tcgcgctttg cgccgccgcg tcatggatct ccctactacc gtcgtgcgaa aatactggac 161880
ttttgcgaat cctaatcgca tcctgcatca aagcgtcaat cagactttcg acgtgcgcca 161940
gttcgtcttc gataccgcgc gtctggtcaa ctgcgtggac ggcgatggca aggtgctgca 162000
cctcaacaag ggctggctct gcgctaccat tatgcagcac ggcgaggctt cggccggcgc 162060
caagacgcag cagggcttca tgtctattga cattacgggc gacggggagc tgcaggagca 162120
cctctttgta cgcggcggta tcgtcttcaa caaatccgtc tcctcggtgg tgggctccag 162180
cggacccaat gagagcgcgc tgctcaccat gatttccgag aacggtaatt tgcaagtgac 162240
ttacgtgcgg cattacctga aaaaccacgg cgaatcctcc agcggaggcg gtggttgcgg 162300
cgccgcgtct accgcttccg ccgtctgcgt gtcctcgctg ggtggcagcg gcgggactcg 162360
cgacggccct tctgcggagg aacagcaacg gcgaaggcag gaacagcgtc acgaagaacg 162420
gcgcaaaaag tcgtcctcgt ctgccggtgg tggtggaggc ggcggcgctg gtggtggcgg 162480
tggcggcggc gggagcggcg gtcagcactc ctcggactcc gccaacggac tgctgcggga 162540
tccccggttg atgaaccggc agaaggagcg gcggccgcct ccctcctccg agaacgacgg 162600
tgagtcccgg ccctcctcgc gtcacggtgc tttccgagtg gactcgtgag cctcccgtag 162660
cgcacgagcg agcaggcgag cggtgttggt gcgctggtgg ttgtgtggat gataaccatg 162720
tgctttttcg tgcgctatgt gtcgtcccgt ctgtaggctc tcctcccctc cgggaggcga 162780
agagacaaaa gaccaccgca cagcacgaag gccatggcgg cggcggcaag aacgagacgg 162840
agcagcagtc cggtggtgct ggcggtggtg gtggcggcgg cagcggccgc atgtcgctgc 162900
cgctggacac gtctgaagcg gtggcctttc tcaattactc gtcctcatcc tccgcggtct 162960
cttcttcctc caacaaccac caccaccatc atcaccacca taacgccgtg acggacgtgg 163020
ccgccggcac cgacggtgcg ttacttctac ccattgagcg cggagcggtg gtttcgtcgc 163080
cgtcgtcgac gtcgccgtcg tcacttcttt cgctccctcg acccagcagc gcccacagcg 163140
cgggcgagac ggtgcaggag tccgaggcgg cggcgacggc ggcggctgcg gggttaatga 163200
tgatgaggag gatgaggagg gctccggctg aggcggcgga ggcaccaccg cagtcggagg 163260
aggagaatga ttccaccact ccagtctcta actgccgtgt tcctccgaat tcgcaggaat 163320
ccgcggcgcc tcagcctcct cgcagtccgc gttttgatga cattatacag tcattgacca 163380
aaatgctcaa tgattgtaag gagaaaagat tgtgcgatct ccccctggtt tccagcagac 163440
tcttgccaga gacgtcgggc gggactgtcg tcgtcaacca cagcagcgtc gcgaggaccg 163500
ccgcagctgt ctccgcagcc ggcgttggcc ccccagcagc cgcatgtccg ccactcgtca 163560
ccaccggtgt tgtaccctca ggttccgtcg ccggtgtcgc gcccgttgcc gccgcaatcg 163620
aaacaccagc tgctcctccc cggcccgtgt gtgaaatcaa gccctacgtg gtaaaccccg 163680
ttgtcgccac cgccgcggct gccagtaact cttcctcgtc ttcttcggct ccactgccgc 163740
cgccgccacc accgtcgggc ggacgtcggg gtcgggcccg gaacaatact cgaggaggcg 163800
gcggtggtgg cggtggtaga aacagccggc ggcaggctgc atcgtcgtcg tcctcctcct 163860
ctcggagatc gcgacggaga aacaaccgcc acgaggacga ggaggacaac gaccctctgc 163920
tccggttgtc gcaagttgcc ggcaacggcc gccggcgagg gccctcgttc ctcgaggacg 163980
gactcgaaat tatcgatccc agcgaggagg ctgcgatcgc cgccgcctcg atcgcggcgt 164040
ttttcgacga ttaaaaaacc gagccgagac cggaaaaaat atgaaacagg acgcgcttgg 164100
acatttgggt ttccacccct tttggtgtgt gtctatatat attggtcact gatttttttt 164160
acaataaaga gatagacatc acagttcacc accttgtctc cccggtgtgt ctattatcat 164220
caatcaccca cagagtcgcc agtccatggt ctctcggtaa tgcgtgtcca gatacgcgtt 164280
ggccagtata aaatggtcgt tgcccacgaa ggcgcgggtg gtgttgcgcg gcgacgggtg 164340
gcaggacttg agtaccaagt gccgccgtcg gtcgatcagg tactcgcagg tgtgcgcgtc 164400
ggcgccccac agcatgaaca ccagatgctc ccggcgctct gacagcctcc ggatcacatg 164460
gttactcagc gtctgccagc ctaagtgacg gtgagatcca ggctgtccgt gcaccacggt 164520
gaacacggtg ttgagcagca gcacgccgcg tcgcgcccag gcgtccaggc aacccgaggc 164580
cggacgctga aacccgtcca ccgtacgcgc cagttcgcga aacacgttgt tgagggaggg 164640
cggcggcggt cggcccgcca gcgtgccgaa ggccaggccg ctggcgctgc cgtcgcagta 164700
cgggtcctgg cccacgatca ccacgcgcac ctgctcgggc ggacacagat agctccagcg 164760
gtgtacgtgc tcgggtgccg ggtacaccat ctcgagttgc cgcgcgccct ccaccgccgc 164820
caccgtgtcg cgcagcagca ccgtgtcgtg gtcgggcaag ctgaggaagc ggatccagtc 164880
ggcgctcaga caaaacacgc gagcctgctc gtcgggggtt aacagagagc ctttattatc 164940
agcaatgtta gcgagcatcc actgcttgag ggccatagcg cgagtgagcc ggcaggttga 165000
cgcgcgtctg cttcagctcg ggcggcagtc cggcgtagta tttatctagg tggcgtagta 165060
gcggcgggtc cagctggtga cgcaggcaga attccttcac tgcgttgtac aggccgtaaa 165120
agagtgtgat gccctcgggc gcggcagcgg tgctcacggg cagacgcacg gcgcggttgg 165180
tacgcgtggc ttcgttgcgt atggccacca ccacgttaaa gagagacggt ggcaccagct 165240
cgaagcctaa cacgtgttcc gtgaagatgc tgcgcccgta tgacagtcgc gtgaggtcgt 165300
agccgcggca caggtcgtcc acgcacgtgt acacggccgg cgagccatcg ccgcactcgc 165360
tgtagccgcg catcaccgtc atccagcgcg gcgctgtgtc cgagctcaac agcgtcagca 165420
gggcccgcaa ttgatccgga ttgttgtaca gcagggccag agtgtccagg aaagcatcgt 165480
ccaacagcac ggagttggcg gcctccggcg taacgggacg gtaacgaata agttgcgata 165540
gcgggccatc gcgtctggta acattcacca acgggcgcag ccaactttca tacttgtcac 165600
cctgaaacac ctcacccaac aggcatcgac gcgttagttc ggggcactcc gcggggactt 165660
tctcggcggc ggtaggagcg acgctgacgg cgactgagga aacaatgggc agcagaaggc 165720
aacaccacag cagtaccacc ggtccaggtg agaaagagaa gccgcaatcc gggcggcggc 165780
acatcaagtc tgcggcacga tgagagtgtg acggtaagga gccagttggc gccgaaagtt 165840
ggcgctcagg tcttcgatcc ctaaaacgtt atatattgca tccagcaggt gagccaggct 165900
aaacggattc acgtaccagg tttggttacc cgcgacgatg acggccagac cgtgggcgct 165960
acagttggag aggttcctgg gtacgaaggt aactgagtcg atgtcgcgcc acggggggaa 166020
tgagacagac gactggcgca cgctgtaatc acaactgtga ttgacgtgta gcgtgtaatt 166080
tcggttgcac tcagcctcga agtagagggg gaaccacagt tcgtcgtact cgtcgtcgtc 166140
ctccagttct ggctcttctt catccaccgc aatgtctacg ctgctctgag attcctcttc 166200
gtacaggatg attgacaggt tatggctaca caggtcctgg gcgggaggac gcgtgggagc 166260
gcgggtggtg gtaatgtttt ccagatcgtc aaaagtcgga gtgtagtctg acgccgtgac 166320
gacaccgtcg acggagatgg tagaagttgc ggccggtgtc acggtggtaa gtatggatac 166380
agaaggggag ggggaagtag cgttcgtacc gatggttgtg gtattattat tccctgtgtt 166440
tcttgttcca gaaaccgttg acgttgagat gggaatcgac gtggtgctgg acgtcagatt 166500
gctgaccgag gaaaccgtgg tgggagtggt gacggtgtta ctcgtggttg aagtgacgtt 166560
aggggaggta gtagtggtac cggtggtggc gacggtagtg tttgtcgtgg cggcggcagc 166620
ggtggtactg gtaacggtgg tcgcgttggt ttccaccgct tcacacagta agcaaaagca 166680
cagggccggg aaaagcaacc agccccgcca tcgccgccgc cgcttcatga ggtgggcagg 166740
cgaaagctgg tgaattcgtt gtacagcggc aagtggggcg ccgcgatcga agggtacgtc 166800
aacaagctga cgttgatatt aaatacgtct ggctgctttt ctacgatgga agcgcacagg 166860
gttacggcgt caaacaggtc tttcttggtg gcgcccgaga cccacatctg gtatacaccc 166920
gtctcgtggt acgaagtaga gcgcggcacc accggacgga tgcagtccag aacgcggttg 166980
ggatcctggt gaaagaattt gaacgtggct acggcctgtg gcgtgtgcgg catcgtctgc 167040
gtgatgagct gctggcccgc taacacggtg acgttgtgca acttgagcag ggcactcttg 167100
agggcctgga aagcgttgcc gcacgaggcg ctgatctgca gctgcacggc cgtggagtcg 167160
tgcagccgca tgagacgtga tacctcttcg aagacgtact tgtatttgct ggcaaaaagt 167220
ggcgcgtacc gacagtcggc cggcaaaatg taggtggcgt taccgccgtt ggtggccacg 167280
gcgggcgcag cggccgcgga ggccggcgta aacagcgtca gcggccggtg gtggctggta 167340
aggtcgatca tgggcggcgt ggtgaccgtg gcggtggcgg gcatgacggg gtttgcggcg 167400
acgggcactc cggccacagc ggcggccgcg gcggccacgg cggcacttgc cgagcccaca 167460
cccgccggca gtcctccgcc acccatgacg ccgccgggca gagcgtcgcc cagacagact 167520
tccgcagtgg cgggcgcgct ctcagcggtc agtacggttt gccgatcgac ctcgcgacga 167580
aagctggtga ggaactcact gtgatccatg gccgcagggc ccgagatccc gggattctgc 167640
gggtgctgac cgagtgcggg gcgagttata tggaagacga ttagcttgga gcggagtttt 167700
gcgtccctag ctgacctgcg gatcagcgac gtgccatagg gatagactgt gagcggcggc 167760
cgcaacggcg gggtcggccg ccgctcgtcg tcacggggcg gcgcgaggga ggaggaggtg 167820
gtgggtacga tcttgacgtg gttgacgtcc tgcccgtccg ggggaatacg caaaaaaccc 167880
cgtcgcggcg ctaccacgat ggtgcgatgg gtctttctct tgttggccgg ggccagggac 167940
ttgcagatgc gtgtggagcc gtagacgatc tggacgtggt cctgggagaa catgaccatc 168000
gccgccaacg ctcagcgggg ggacgtgttg ggaacacaga ggctgaggga aaactccgta 168060
gaagtcagcg aaataaagac aacacagcag ccactcctct cgtctcgggc cctaccactg 168120
cttgaagtag ggcaccgggt gtttcttttc ctcaacgggc tcctccagtc tcttatagga 168180
ccagtcccgc cggcgcgcca gcatgtaggt cacgtacaaa agaataatca ccatgaacac 168240
caggaaagcc agcacgccgt aggccagcag ccggtcctcg aacagcgggt cgctcttgat 168300
aaacacgtag gtggtggtaa aacttcggcc cgcaatctga acgtggagac gcacgacagt 168360
atacgtgccg ttgaggtaga agacaaactc gcgtaaccgt tgtccgttat acgtcacgtt 168420
actaatattc cacggcggaa tgagctggtt gccctgatgc agatgcacgg tgctgttggg 168480
gtgatagagg ctgctaccgt tgagcaagca gtgttcgtgt tcctgaagca gcacgcggac 168540
ccgcatcgtg gtggcgttca ggcgagtccc gtacacggcg tagatgggat aggtgaaaag 168600
gtcccaagtg gcgttgtgat ggcggcccca gctgaagaaa gagcacgtgt actcagtggt 168660
ctcctgcggc ctgagtcccg agataagcag ctcttgagca gtagcgttgt aggagagatg 168720
tagttttcct gtggataaaa ttcataagtt gtttattttg ttggcaggtt ggcgggggag 168780
gaaaaggggt tgaacagaaa ggtaggtgct acttaccttc attatcgggg gggaaggcgc 168840
taagataccc cacctgagtg aagggaccct tgcagtctgt ccgtgcataa caagtaactg 168900
ataaaatgtc tggatttttg gtgttattca acaggataac tttgcaggtg gcgtttagag 168960
acacttggtc gtggctgtag ctggcttcgc aattcacagt atacaggtgc ccctctttct 169020
gcgtcgtggc tatcacggaa gtggaggcgg acgaggtaga ggtttgtacc gtggtggtga 169080
cagcagaagt gacgttgtta gaggtactta ttgacgtagt agacgtgacg gtggtattac 169140
taggggaagt gacggcgctt gtggtgctac ttttcacccc cgggtgcatg tcgcccaaga 169200
gcgcaactac gagcgcgatc gccagtacgg aacacatgtt gccgtgtgac gagacggcgt 169260
gtggacgagc tatatgtggc aggaggtcgc gtcacctctt gtgacgccta aacgtccagc 169320
tccagataaa agaggcgtta ataatgaaga ccacaaaaac cacttgcgtc agtatgacaa 169380
tcataaaggc tcggtgattg ctacgcctaa agtacgcggg attatccacc agttcatcct 169440
gctgaacaaa gtggatgatt gacgtattgg tgttactatc cgtgttgttg accatggatt 169500
tgactaagaa agtcttggcg ccaaaagtcc cgttagagcc ccagcaggtg acgctgctat 169560
tcacataagt tcccggtgcc cccgctagca tgtatttcag ttggtgggta taattttttc 169620
tgtcgttatc catgtcattg ctgtagttga ccttgctggt gagaaagcgt gttttcaacg 169680
gggcacttat catcatccct gaggccaaaa agggcgaatt gcaagctgta gtgttacaaa 169740
aaatagtcaa gttagtgtca ttgtattgat aaatgtaagc catgcttact tcaggctcat 169800
accacccgat tccaatcgcg gccgccatcg ttaccacgtc ccatcttccc agacttacca 169860
ccgccaccac taacagcgtc acccccgcac ggtacatagt taccctctcg acgtcgccgg 169920
ctgtcaatga cgtgcctgcg tcagtggcta tgatttatag cttttgggcc caaccgcaac 169980
ggatctgtcg taatctacct tccacagggc cgccgcgacg atgctgaacg acaggatcag 170040
acagacggcg tacaaaagtc ctaggtcggc gtcgacgcgg caggtgcgga tgtctcgcag 170100
ggtgggtaga tgggcgatgc acaactcttt ctccccccgc ccgtacatcc catcttgtat 170160
cagcagccgt agcgtggcat tgatggtcag cggggtaacc aaagaaatca catagggatg 170220
tgtacaggaa gtgcagtgac gggtatccgt gagatgtaag tcaccaccct cctcaccgtc 170280
atcatgaaag accaggactc gggtgagacg acccgatgaa tactggatct cccaccacag 170340
tctttggtcc aacaccgaga gggcgcaaga gattctaagt ctccctgggt tgggggagca 170400
gatgtaagtc ccgtatgtgc ctctcgccat cagggccata cacatgaggg ggagaaggac 170460
aattatccgg gaccacccgc acccccacat cacgagacca gagacggaga tgtataaaaa 170520
aagctacttt tattaaacag cattctcacc acacgttaat actgtcacgg ggaatcacta 170580
tgtacaagag tccatgtctc tctttccagt ttttcactta ctgagacttg ttcctcaggt 170640
cctggatggc tgcctcgatg gccaggctca gggtgtccag gtcttcggga ggggtctcgg 170700
tgggctgctc aaactgcccc acggcgtagg ccttcgcggc cgtctcgtag ataggcagca 170760
tgaacccacc ctggttggtg gagaagatgc gcaccatgac ctgtttggga aacttttgca 170820
tcaggggcag gcacaggttg agagcgccca acaggtccac gggggtggca gcgtggatga 170880
tcatgttgcg gtaatcggag gaacgggggc ataattggtg ggtgtgcaat tctttgaggc 170940
tccacgcggc cttgacgcct tcgttacaag catcggctgt gcgctgcgcc acttcgggtg 171000
gatgtgtcac gggcatggtg tgctccatga ggaagggagt ggagagggcc aggttgcaca 171060
tggtgcccag gcgacaccgc accgcatcca cctcactctt cacctcatga ttgcgggtgt 171120
agataatctg gatgcccttg ttgttcacct gcatggtttt gcaggctttg atggcctcat 171180
ctaacacctg gtgcatactg ggaatcgtga agggcaggtt cttgtactca agagagcgat 171240
tggtgttgcg gaacatgcgg ctcacctcgt caatcttgac gcgaccccgc cgagtctgca 171300
cgttgggtgt gcagaagggg gtgttcttat ctttcatgat attgcgcacc ttctcgttgt 171360
ccaactcgga gatgcgtttg ctcttcttct tgcggggtcc ggtgctcgcc ccgccgctgc 171420
tctgatggcc gcagctcagc agagaggagg aggccgcgcc accaaaaccg ccgcgcccat 171480
ggtggctcga ggtcacggat gctcctccgc cactgctgca tttcatctcc tcggactcac 171540
tctccgagtc cgaagccgaa ctgcaggagg aggaagacga agaggaacta tcttcatcgg 171600
gccggcccaa gggatcggga agaggagggt ggttcatctg ggagagcggg tgcgtgggag 171660
aggtcactcg cggcgtgccg ctgccggtgg aaggggaaga cgcggtagca ccgcgggttt 171720
cgacttcttc accctgttct tcctcgctat cagagatcac gatacagccg gcggtatcga 171780
taatcttgtt gcggtactgg atggtaaagt cgggctcggg cttgatgtct tcctgtttga 171840
tgaggggcag catgataggc gcgggaggca cgggcggttt aataatcacc ttgaaaggac 171900
gcgtggtttt gcgcggtttc ttacgcgggc tgagctcggg agtagcggat gccccgggga 171960
gaggagtgtt agtaaccgcg acgctggtgg gggtcggctt gttaagaggg gcgctgctaa 172020
cgctgcaaga gtgggttgtc agcgtggggc cggtgctact ggaatcgata ccggcatgat 172080
tgacagcctg ggcgaggatg tcacctgatg gtgataagaa gacacgggag acttagtacg 172140
gtttcacagg cgtgacacgt ttattgagta ggattacaga gtataacata gagtataata 172200
tagagtatac aatagtgacg tgggatccat aacagtaact gatatatata tacaatagtt 172260
tactggtcag ccttgcttct agtcaccata gggtgggtgc tcttgcctcc agaggcggtg 172320
ggttcctcag caccatcctc ctcttcctct ggggcaactt cctctatctc agacactggc 172380
tcagacttga cagacacagt gtcctcccgc tcctcctgag caccctcctc ctcttcctca 172440
tcactctgct cactttcttc ctgatcactg ttctcagcca caattactga ggacagaggg 172500
atagtcgcgg gtacagggga ctctgggggt gacaccagag aatcagagga gctgacacca 172560
gcggtggcca aagtgtaggc tacaatagcc tcttcctcat ctgactcctc ggcgatggcc 172620
cgtaggtcat ccacactagg agagcagact ctcagaggat cggcccccag aatgtactgg 172680
gcaaagacct tcatgcagat ctcctcaatg cggcgcttca ttacactgat aacctcaggc 172740
ttggttatca gaggccgctt ggccagcatc acactagtct cctctaagac atagcagcac 172800
agcacccgac agaactcact taagagagag atgcccccgt acatggtcat catacaagcg 172860
tcactagtga ccttgtactc attacacatt gtttccacac atgtagtgag gatatccata 172920
aatatgtgat caatgtgcgt gagcaccttg tctctctcct catccaaaat cttaaatatt 172980
ttctgggcat aagccataat ctcatcaggg gagcactgag gcaagttctg cagtgccgcc 173040
atggcctgac tgcagccatt ggtggtctta gggaaggctg agttcttggt aaagaactct 173100
atattcctgt agcacatata catcatcttt ctcctaagtt catccttttt agcacgggcc 173160
ttagcctgca gtgcaccccc caacttgtta gcggcgccct tgctcacatc atgcagctcc 173220
ttaatacaag ccatccacat ctcccgctta tcctcaggta caatgtagtt ctcatacatg 173280
ctctgcatag ttagcccaat acacttcatc tcctcgaaag gctcatgaac cttatctaag 173340
atatctaagg cattctgcaa acatcctccc atcatattaa aggcgccagt gaatttctct 173400
tccgtctggg tatatttttt cagcatgtgc tccttgattc tatgccgcac catgtccact 173460
cgaaccttaa tctgtttgac tgtagaggag gataacaaca catataagta tccgtcctcc 173520
tgactcattt atcgctatct cgatgccccg ctcacatgca agagttaatc tttactctat 173580
ctgacataca caagtaaatc cacgtcccat gcaggttagt atacatcaca tacatgtcaa 173640
cagacttacc gagttctgcc aggacatctt tctcggggtt ctcgttgcaa tcctcggtca 173700
cttgttcaaa agttttgagg gattcttcgg ccaactctgg aaacagcggg tctcccagac 173760
tcagctgact gttaacctcc ttcctcaaca tagtctgcag gaacgtcgtg gccttggtca 173820
cgggtgtctc gggcctaaac acatgagaaa tagagtcata agcacatggg tcacatacag 173880
gagatatgta tataacatta atacaatttt attaaaaaaa aagggggggc acaaaccccg 173940
acacgtaccg tggcaccttg gaggaagggc cctcgtcagg attatcaggg tccatctttc 174000
tcttggcaga ggactcttcc ggttttagaa gctccacatc gaagacgaga gtggcatgtg 174060
gtgggatgat gcctgggtgc ccagtggcac cataggcata atctggagat atagtcagtt 174120
tggctctctg acccacactc atctgggcaa ccccttcttc ccagcctcgg atcacctcct 174180
gcttgcctag cataaactta aagggcttgt ttctgtcccg ggaggaatcg actttctttc 174240
catcttcaag catcccggtg tagtgcacca cacaggtctg gccgcgcttg gggaaggtgc 174300
gcccgtctcc tggggagatg gtttccacct gcactcccat cgtgtcaagg acggtgactg 174360
cagaaaagac ccatggaaag gaacagtctg ttagtctgtc agctattatg tctggtggcg 174420
cgcgcggcag caacgagtac tgctcagact acactgccct ccaccgttaa cagcaccgca 174480
acgggagtta cctctgactc ttatcagaac acaacaactc agctgcctgc atcttcttct 174540
gccgctgcct taagtcttcc aaatgcgtca gcggtgcaag cccgctcccc gagctcattt 174600
tcagacacat accctaccgc cacggccttg tgcggcacac tggtggtggt gggcatcgtg 174660
ctgtgcctaa gtctggcctc cactgttagg agcaaggagc tgccgagcga ccatgagtcg 174720
ctggaggcat gggagcaggg ctcggatgta gaagctccgc cgctaccgga gaagagccca 174780
tgtccggaac acgtacccga gattcgcgtg gagatcccac gttatgttta ataaaaactg 174840
cgggcactgg ggacggtggt gttgtatatg tgaatttgta aataataaat gagaccccat 174900
cctgtaaaaa tacagagtcc gtgtcagtct ctgaaggaca gtgtattggc atatagccaa 174960
taaagagagt tgtggcaaag agccatgtta tggattagta atggaaagta tcgtcaccaa 175020
taggggagtg gtcaataatg gtcaataacc cacacctata ggctaagcta taccatcacc 175080
tataacatga ggaagcgggg gtgtatagac cccaagccaa aaacagtata gcatgcataa 175140
gaagccaagg gggtgggcct atagactcta taggcggtac ttacgtcact cttggcacgg 175200
ggaatccgcg ttccaatgca ccgttcccgg ccgcggaggc tggatcggtc ccggtgtctt 175260
ctatggaggt caaaacagcg tggatggcgt ctccaggcga tctgacggtt cactaaacga 175320
gctctgctta tatagacctc ccaccgtaca cgcctaccgc ccatttgcgt caatggggcg 175380
gagttgttac gacattttgg aaagtcccgt tgattttggt gccaaaacaa actcccattg 175440
acgtcaatgg ggtggagact tggaaatccc cgtgagtcaa accgctatcc acgcccattg 175500
atgtactgcc aaaaccgcat caccatggta atagcgatga ctaatacgta gatgtactgc 175560
caagtaggaa agtcccataa ggtcatgtac tgggcataat gccaggcggg ccatttaccg 175620
tcattgacgt caataggggg cgtacttggc atatgataca cttgatgtac tgccaagtgg 175680
gcagtttacc gtaaatactc cacccattga cgtcaatgga aagtccctat tggcgttact 175740
atgggaacat acgtcattat tgacgtcaat gggcgggggt cgttgggcgg tcagccaggc 175800
gggccattta ccgtaagtta tgtaacgcgg aactccatat atgggctatg aactaatgac 175860
cccgtaattg attactatta ataactagtc aataatcaat gtcaacatgg cggtaatgtt 175920
ggacatgagc caatataaat gtacatatta tgatatggat acaacgtatg caatggccaa 175980
tagccaatat tgatttatgc tatataacca atgaataata tggctaatgg ccaatattga 176040
ttcaatgtat agatcgatat gcattggcca tgtgccagct tgatgtcgcc tctatcggcg 176100
atatagcctc atatcgtctg tcacctatat cgaaactgcg atatttgcga cacacagaat 176160
cgcccaagtc accaaagtcg tctatcgcca tcccccgtaa acgatataag cgctatcgcc 176220
agatatcgcg tatgcccaaa aatcactttt ggaaaaatgg cgatatcagt tacacagaaa 176280
ctcacatcgg cgacattttc aatatgccat attttcaaat atcgattttt ccaatatcgc 176340
catctctatc ggcgataaac accactatcg cgcgacatga atttagtcgg cgacagaaat 176400
ctcaaaacgc gtatttcgga caaacacaca ttttattatt cactgcagca tatagcccat 176460
tttagcgcgg cacacatcca gccgtttgtg ttttttaacg ctctccaggt actgatccag 176520
gcccacgatc cgggttatct tgtcgtattc caggttgatc catcgatagg gaacgctgcc 176580
agcggcgccc agcaggtact gcgccttgtc gttcactttg ccgcagcgta ttcgcccgtc 176640
agcttcgagg tataacctac aacacggagg ggaagggggg gtacaaaacg tgaaattaga 176700
cttttttttt aatgatgttt tgtccctctg tcttactttc ccataggctg taaggccctc 176760
gaggaagaga cttacggatt gtagttgcag ctcgtcagtt tgttgtgtac gacctggcgt 176820
gtcaatgaat gggtcatggt ggtgacgatc ccgcgaatct cagccgtttt ctcgggactg 176880
tagcagactt cgccgtccgg acaccgcagc ctgtggattc atgaaaatct actctggcat 176940
tcccgaggat cgtcgatgga acatggctat cagaaacgtc gagagacaaa tccagacgca 177000
ccacagaacg cagacaatca taaaaatacg tacgcgacgg tgaagcgatt gcacattttg 177060
aaatcgtaac agcgttccgg cgggtggttg acgtttatga attcgcaaca ttcttctgcg 177120
cgcacccgcg gcacgcggct gtgacccaat agcagccaca acgtcgtcaa gaacggcgtc 177180
aggtctttgg gactcatgac gcgcggtttt caaaattccc tgcgcgcgcg acgggctcaa 177240
acgatgagat tgggatgggt acagaaggtg taagtctggt tattggcctc ggtgaacgtc 177300
aatcgcacct gaaaagacac gctgtagtcc cggaagacgt gggcccagct ctccagcttc 177360
atcacacaca tctgataacg cgtgccatcg ttgacgacga agcgtagcag cttggtctgc 177420
ttgggcacca tgtgcgctcc aaaaatcttg gcgtcttcca cgctgatctg cacgtttccg 177480
tcgctcggtt tcgaagccgt ttggggcatc cgttggagga tggtctggtt gcgaccgctc 177540
agataccaga tcaccttttt cacccaggtg gagcttctct ccaccaaggt ctggccttcc 177600
cggttgtaca gcagatacag ggtctcgttg cgacactcgg gacccgttga tacctgctgg 177660
aaccccgaga attgcaaggg ggaccgtggg ggcgagggat agagaaaagg acagtaaaac 177720
gtcgccgcgt catgcggttt ggaatacgtc agtttagacc atggcgggga cggattctgg 177780
tttgccgtta gcgtcgacca cggagacgcc agacagggcg ttgcccaaac cgcgcacaga 177840
agcaggcagt gaaagtggtg acgaagcaga agccgcagca tattatttcc cgtgacgcag 177900
gctagttggc aaagagccgc acgctgaact cgaggctccg ggcgtgtggc gccagcgaac 177960
cggcggcgtt gaacgtggtc cttttgttgg tgccgccgcg acggttctga cgtctaaagt 178020
cgctgatgag caacgacacc tcggtcacgt tgattctgca agcacaggtt ccaaacgtca 178080
tttcataccc catgcggtta cttagccgtt acccgttcgc ccttaccttc ccgttgtcat 178140
gcacctttag cgcgtaccct cacctcttga gcacgtcaaa gttgtccaag ccgtggctcg 178200
catcgtagtg gtagttcaac gtgaggtcca cgagctgttc cacatacttg taacgggttt 178260
ggtcgggcag cgcgcgagag cacgcgtccc agtaatgcgg tactcggtaa taatcgtttt 178320
tttccgcggt ttcccgctgg cactgaccca gcaccacggc gcacagacaa acagacagcc 178380
acacccgaca cagccgcatg ttgcagactg agaaagaaag ctttattatg agacatcata 178440
cacatagtat aggcgaggtg atggggcggg gaaagagttg gaaccgaaag acaaaaaaaa 178500
aagcctagtc gtactcggga tctctgagcg agacgggttg catggcaact ttcattagtt 178560
tgggaatctg ccagctggtg ctgttcgaag gttcttccat ttccgaggcg gtcagttcat 178620
cgtacaccga aacgtagtac ctgatggggt cctcctcatt gtccgagagg tgagattcga 178680
tggtcaaagg cgagcctctc ccataattgg gattcacgaa cgacgtgtcc aagttgccat 178740
cctttctgaa atagatgacg ttctcaggat catgtttcat gcgctcgcgg gccgcggacg 178800
cctcctcctc ctcgtcccag tcccgagttt ccaaccgctg ataagggctc gaggaacaaa 178860
atccggcggg gatctgagaa cctcgtcggg aaccgctgcc aaacgggctg ctgccgccac 178920
tgtcgtccgt gtcgtccaac aggttgacgg cctcttcgtc ggcgaaacga aagcggcccg 178980
ggtgcttgca acacgaggag taaactaccg cgatcagtac cgctatgaag ctgaaaatgg 179040
aggtgcctgt cacgatgtag aagaggatag ccagcacttt catgatttcg tcattgcgcg 179100
cgtcgtgaac ggaagattcg cgggcagtgg tcatgttggt ttcggttgta ggttcgctac 179160
tcgtggtgct ctcgacggta tttctgctgc tggtgctagt agggacgttt gtgctgctgg 179220
tcatatttgt agcgtcgctg aagtcgatgt gaagcagcaa cccgaacgcg accaggacca 179280
ggaatgttgc gcgaaggaga ccccgcgggg ccggcattct tgagacgtgg cgacgtggat 179340
ttcttgttat gtccgcgaac gacgtgtaac gaggacgtgg tttccgcaag cctctaccga 179400
cgccgcgaca ccaggtaggt tatcaaaacg cgagcccata tcgccgccat cattgtaatc 179460
agcaatgtgt tgaggtactg cacgatgaat ctgtctagtg acaccagcca accctctgct 179520
tttgcgggca agcgcgcttt cggtgacagg gtgtatcgta cgtagccgcg ggtcaggcgc 179580
gcgttgtagc ggtacacgca gaaatctatc cacaggccaa cgcccggctg tagcttcgga 179640
tggtggataa tagcgcggtg acgtacgccg cgtggcttta gaatctccac ctgtaaggcc 179700
atctcctcca ggtagtgggt ctgactgcga cgcagcgtcc agttcatgta aaagtcggtc 179760
tcgccgtgtc cggccacgaa gaggctgctt actaatccag tctacattgt gccatttctc 179820
agtctgattg cattttttag agttatgttg ccaccaacgt atcctgttac gttgattacc 179880
tcgtaactgc ggtcgcatct tttatggact gtataattga aaccatcaca agtaacggtc 179940
gtggtggtgt tggtacatgt ggtagtctca acgtttgtat ttgtcgttgt ggatatctgt 180000
gtggttgttt tcgacggttt tgtagaaacg gtggttgctg gtgcagttgc agtagagcaa 180060
tttatagatt ctgaagtgct tttattgctg ataactgttg tactgtatgt tgatgtggct 180120
gtctcagtac tagtggaata gttaacggta gtactacagg gacattgaca ggaacaggtt 180180
tgattgcagc tttctgataa cgcggatatt agtatcgtcc acataaccgt aaatcgccag 180240
tccattgcaa tattagttct cgctcaatgg gcattaatat tcctttgaac gctgagcctt 180300
acagaatgtt ttagtttatt gttcagcttc ataagatgtc tgcccggaaa cgtagctcaa 180360
tcttcatgtt ctgtgtgata tcgaacaatg aattctgatt cactgacggt gtcttgcaac 180420
atatggtact ttttgttaaa ggctcgtcgt gcaaaaaaca gaactatgca ggccatacaa 180480
accaacacga tggtccatac ggtgcggctt ctttgcgagc tatgatagag attacgtttg 180540
tggtgatgtg tattgttagt atgttgactt cctttctctc tatcttcatt ttcgatatcg 180600
gtgttgtatc tagggcaaac gaaagtagca ttaatagctt cagtatgatt ttttggtgtt 180660
actaataggt agaaattttc atcttcgtga tgtcctgtga agtaattttc tttaaaacaa 180720
cgtctgctgt acctgccgga attggtgata tttagatcgt acagatgtag ttctgtgttg 180780
ttgcacgaac gacataagtc atggtacagt gaaggtcttt catgttgaga atgacataca 180840
gtatgagagg taaggatgcg taaccaatac caagattggg tatgtgcgtt cttacgatga 180900
cctagatgat gtccgtgtgt ggatcgattg taatgtcgta tccaggcgac tgaaagacaa 180960
tcccacgtag aattaccttt tatggtgaca ttactccctt ctattcctgt tgtattagtt 181020
tctttgaaac gtatgattgt tgtctctgtg tgacaagcgt tggaagagtt agtacggttg 181080
tacgtggtgt acgttgtggc gctgcaattt gtaagccatg gcgtgcttat aagtgcagta 181140
ttagtggata cgttgtgcga agtttcatct gacgtgatag ttacggtgat tgttgtgtta 181200
taagatgatg tagcgtttgc tgttacgttg gtaaaagata atatagtgtt ggtatttgtt 181260
gaaatcaatt ctgtagtggc agccgtattg gatatattag catatgatgt attgaatgta 181320
gaatatacgg ttgtgaaagt actcaagtcg gaggtaacgt tggtgatgtt gccaatggtt 181380
gacgcttgtg aggtgacaga tgtgtgtggc gtcgttgatg tgttgttatt cggagtagaa 181440
aatacgctgg tcacaaaggt ggtagaagca gtgttgggtg atgtgatgga tgcagtattg 181500
gtagtagtac tgttgcatgt aactctatgc agaatataga atattatgat tgtatacgcc 181560
gtatgcctgt acgtgagatg gtgaggtctt cggcaggcga cacgcatctt ttactgtaaa 181620
tccccgtcca ccgtcaacaa caaaggttcc gtatctaggt ccgtccgcag atgttcagcg 181680
tcctgttccc cgattcgttg cgatcgcagg aagcagatga ccagcgcgcc aacaaagatc 181740
atcattcccg aaacccaggc gcaatggagt gagaggccgg accactggcg ttttaaatcc 181800
gagataattg cccggtctgc ctcttgggaa tccgtaacca caactctccc tggtcccgga 181860
taaaagcatc gacgcgtttc caaggctcgg cagaagctac gtgggtggat gatgaggtag 181920
aaagcctcga catcgccggt atactgatcc tgcaggaggt agactcccgt atctttaacc 181980
gtgagattgt acagcgtcag attttggcgc gtgcacgcga acgccgcacc gccctgacgc 182040
gtggtttctt tataggcgtc tgtaatgata caaagtggcg gcatacgacg catgtatctg 182100
ctgtagatat cataacgctg ccagactacg ctgtgatggc tagtgttaag cctggtaacc 182160
agcgtgcgtg tacggtcctc gcaggtggca cggtagttgg cgagctttag gggttttttg 182220
gttggttcga cggcgttcga tgaacttccc tgagttgtga acaaaaacag cgacgtgact 182280
atgacaagcg tgaggggggt gctgtaggtc tgcatggtgc aaaacacgtt ctcgccttcc 182340
ttatcagacg ttgtcgtcct cgtcctcttc gtcgtctgtg cccgtcggtt cgatcaacgg 182400
ggagttatct ttctgtctgg agggtcggta tggaatccgt tcgtagatgt tctgcttttt 182460
agccgcgtgt tgttccagct ttttgcgtgt caggctccga taggccagac attgatctac 182520
ctcggtgccc gtgttgtttt tctcctcctc gcgcgcgtaa attacaaaga agaccaccag 182580
caggactatc agcgtagcca cgaacgagcc cgcgccccag gccgagtatg cgcctagcat 182640
ggtaatgggt tctgtgatcc ggcatttgca catcgcgtgg cacttgctgc cattgccggt 182700
attagatgat gtgttattcg gactgcactt gcacgtcaaa tgggtatttt ctgatttcac 182760
gagacagttg gtggcgactt tggtttcggc gcagacggcc acatagctta ccaagctgag 182820
tgccagaaag cacaccgcgt gcattacacg cggatacata ttaaaacacc gtgttccaca 182880
agcaccgcac acgtcaatcc tccccgcacg gtcttcagcc cgcccatgac atgatctccc 182940
tcacgttacc cttcaacacc ctgtagtact ctgtctcggc ttccggtccc catgtcctaa 183000
ttataacaaa acaccgtgac actgtccatc tccctgtctt tttgcgccgc cggtcccccc 183060
caaatcatgt ctctagatgc cgccggccac caaccggagg cacggcggct attggattcg 183120
gcattggtgc gccgcgtctt ggcctgcatg atcatcgtca tcatgattgc cattagcatc 183180
tggatcctga cctacgtgct gtttctctaa taagaacccc ggcccctgac ggtaattttc 183240
ctttcttctc cgtttctcct cagctgccgt acgtgatgcc tcacggccat ctccgacagg 183300
ccctctcccc gacctcctgg acatgtgagg gcttgttgct cctcctggga ttgctggtgc 183360
tcttctttca ccaccacaac cagtcggccg tggagaggcg tcgccgcgtc tcgttcgtcg 183420
aggccgatcg actgccgcat gagagcgggt ggtattcttc cgatgacgac ggagaccggg 183480
acggtgatga ggaaactgga gagagccaca acagaaacag cgtgggactg tccgctgttt 183540
ttagctgact ggcgtgcgac ctgtaaaccg ttactcgggt ctcaagatgg tttggaagtt 183600
gtgactcatc ttcctgtggg tgatacccaa ccggacgcga gtgttccata aaagccgggc 183660
gctccggcga gaccatgcca tcctcgcctt cggacgcccc gctcctcttc tctctcctct 183720
cctccccgct gccgcggcca ttgccgccgc cgcccatacc atcggcatgt cggccgacaa 183780
atcgcagctg tcttcgccgc cgcagctgta gcagttaacg tcgccggcct ccaggaggag 183840
atggcgctgt gcgtcgtctc ttcgtcccgt ctccctctgt ggtcgtgggt ggtgcgagag 183900
tacacgatgg gtggctctcg tctcggggga ccacaggggg aggggggtaa tttattattc 183960
gtattactgt aattttgtat cgcttaattt gtttagagcc gcacgcttga caacgccttg 184020
tatagcctta tttatcccga tgactttttt ctccgtacaa gaaatggacg tcacttgagc 184080
agacacagtt tcatcgacca cgacagtctc atgatctgac tacctctgac ccgccaacga 184140
gaaaaccgaa aagtaaaaga tgaccgcgcc ctcggagtcc ttttttcctt ttcaatcatg 184200
aaagcaagag gcagccgaga gaatgccagt aagagacgac catcgcagac acagtacgat 184260
actcatctta gaacgaacca gcgaataacc atcacacgta cagcagaatc tcatgaacta 184320
gtcaaccaac gtcataaaat cttcacacaa tcgtttttgc gaacttttag gaaccagcaa 184380
gtcaacaaaa gactaacaaa gaaaaaccat cttggaatta aaaaaagtag catcgttacc 184440
ttatgaacca gcagcattca gtatatacac cagatataat atatttatta atgtatcctc 184500
tctttctcct gatgtaattt tgtttttgta aattcaattg ttgaaagtct ctccctgggg 184560
gaattgcata tcttattgat gaagaagaaa tccctgccat atgtgttgtc aaactatcat 184620
tatttctcta tatgggtatt ttttttctaa gaagcaaaag actagcagca gccaaaataa 184680
acctgatgaa atctttaact gaactcccag tggtctgtgt gtatatttct gttggtggtc 184740
ggttgtctga acccgggtgg gttgttcgga aacggcggga cggggaaacg gatggaaaca 184800
gcgtcgctat atacgtgact tttgatctaa acggacgtcg ctaggctgac agtttacgaa 184860
ttgctaaaca agataggaac aaaacaagcg gggctttgcc tggtaggatt tcctgtggaa 184920
acaataaccg gatgtgattg tggctggtac ataagctggt tctggctgca agcgcttttc 184980
actgcattag gtttggcgtt tgcttttgcc tgggaacgct atggctataa cgggaaagaa 185040
ccggtttggc aacattccat tgtggggggg gggtacttat agcgtgccta gctatgacgt 185100
tgatatatgt ggatgcggat aatactcgta atgagctaaa agcgacgact ggtagtaatt 185160
ttaccattac gcataggaaa gatccgttga caactaagtg gaaaaccgtt tttggtaaca 185220
atggtgatca gtggttgtgc aacgttacgg gtataggtaa tgctactgtg aatagtaacg 185280
caactatttg tgtgtcgagc tgtggtcata atacgttgga tttatgtaat ttaaagtcgg 185340
gagattctgg cttcttcgat ctgtctcgtt ggttcggtga aaacatggat gaatacagtg 185400
gtgatgtgtg gcacttggaa gtcagctaaa tgttgtatcg cttagtgaat tggtgttctt 185460
acagttttca tgtaataaac tacgtgtaat tcgttaaatt tgtgtgtttt tttgttagta 185520
ttctgcgtaa cggtggaata aaattgcgtt gacctagtta gatttcctgt gtagaacaat 185580
gaccggacgt gcttggactg gtacatacgc aggggctgga cgtggttacc ggtcactgga 185640
ctcggtttcg ctgtagctgt ggttcaacct gaacatggct cccagagctg ctaggaaccg 185700
gtccagtcac attttttggt gggtgggggg tactaaaaaa gtgtttaata tttgggttta 185760
atgataaaat ccaggttatg gatatgagga aactgaatac ctcgcagggt cgaaatctta 185820
ccacagttga tgatagaaga cggttttcca tcgggtggga aacatgggat aacggtggtg 185880
actaataatg gtacaacggt cgtcaataca acagcctgtg tttcaagttg ttcgcatacg 185940
tcgcttgtgc tttgcaatat gacgcagcag actgattcgt tgtacggagt gggtcatcgg 186000
ttgaatgacg aagaagatgg tgaactgtgg agagtttcgg tttcttaata atcccatacg 186060
acatgtgttc atttatatct gaattttagg atgatgacta tagtataact ctggggaaca 186120
aatatcatac gttaatcact ttaagttacg ccgttaggaa aagaaaatca gtccgaatga 186180
agcatagtca gccgaatgat acagcaatag cttgtttaca acgtgttctt ttttacatta 186240
tgaacgtgcc ttgcttttta tacacacatg gagacagagg tccctcagcc cttgtcacga 186300
caactccctt tttctaaacc gtatgtgctc caaaccgtat ctcctcatcg tcacgtgaaa 186360
taccatggga ccccttttcg tcacacacgt ctttccgctt acccaacgcg tcagcccgcg 186420
ctcggcagag ctaccatata aaaacgcagg ggtttagcag cttccccaga tcgctgctgc 186480
cccggcgttc tccagaagcc ccggcgggcg aatcggccgg ctggtcggtc ggcgctcgga 186540
cggatgggga gaacggcggt gacttagccg cccgtggccg ggagaagacg gaggagccga 186600
gatgacaaca gcagtcgtgg aagggtcgcc aagccccggt ccttctcttc tgtctggtcg 186660
aatcttgttt tcttttttca accgctcttt ttgtcacctt tttatgtgag tttctcttcc 186720
gcgtctcccg gccgtaccat ccacccatgc agcatgcacg cgtgtatgta tgcatcgcct 186780
ctcctccgtc ccgactacca tcagcagtac cactgccgcc acccccagcg ccaccaccgc 186840
tgccgtcgcc accgcgttat ccgttcctcg taggctggtc ctggggaacg ggtcggcggc 186900
cggtcggctt ctgttttatt attttttttt attttttatc ttctcctttc cttaatctcg 186960
gattatcatt tccctctcct acctaccacg aatcgcagat gataaacaag agggtaaaaa 187020
gaaaaaagct acagacattt gggtacctca gctttccgat aactcgaaga attcaaagtc 187080
gacgattccc aacaagagaa aacagaacaa aaacaaggtc atttttattt atcctcatcg 187140
tcaacaacaa ctaccgacaa caacgaaaca ccaccaagaa tgtcaatccg caagggtgtt 187200
cctgccccct cgacgcgcct gtcgcgatcc tcatggcgag gaccgcgatc tccgtatagg 187260
tagatgaaat tatcccgtgt ccggtcctga ttccccgcat gccctgcaca tcctgacgcg 187320
tcggtcagca gccaaacaat cataggaaat gaaccagaag aacaaaaaga tcatctctct 187380
cggtgtatag caacaccaac aacaaccgca tcgcaacatc ttcatccgca agacggaaag 187440
aaaacaacaa taatgagaat gaaatcacca caaccaagcc agatttcacg tccatgagtt 187500
tttattatat tattatcaaa acgaaaaaca gaaaaactgt catagataaa tataaaaaaa 187560
aatagaaacc acaaacgact actagtactc caatcttaga tgtatatgct cctagataag 187620
atttagtatt accataatca tcgaagaatg aaagacgacg atgattcctt accgctcctg 187680
ccacccggtc tgtatgtaga gagagaagag agaaaacggt gaatccaaga tccccgggtc 187740
ggcgtcggca tgccgctgat cgcagtggcc ccacctcggc atgccggcgc cgggcgagga 187800
attgctcatg aaaaaaagta tctttctgta aaaaaagaaa acaatacatg attaaccgaa 187860
aagaaaccaa caaaaagaac ccgagatcag tcgatttcga tcactacgat aaacacatgg 187920
aagatttctt gaaaaaagaa aagagaaaga gaccaccttc ccggcggcgg acacgctcct 187980
ctccgtcgcc gttctgcacc atgattcgat caataacaac atcatcatcg gagaccatct 188040
tttaatcaat cagcgttgca gtagtcgact ccctggacac gaaggagtca tccattttta 188100
tcctcgcact tcttcgctct caaagccgcc tttaaagttg aaatgaaagg atggaaacat 188160
ggaatacagt tttaattgca cgtatcacca ttttactaca aaaagaaaaa aaaacaactt 188220
acacatagta ttaccttagg tttacggata agtagagtgt aggcgttttt gaaacagttc 188280
agccaatgca atcttgtctc ggcataatca ctctttctgc atataatagt agtagtagat 188340
ttattcacat caacacagcg aaaaactcca gcatcaaagt acacctagag acagccctta 188400
aaatatagtt tgcagctttt agatgtactt acaccaaaga agattaccgt ccttacgaga 188460
aaacagatac tcggatatag gaatcaagac agctctgcac tgaaaacaca ctctcctgtc 188520
acgacaccgc gccacaccag aggcgtacgc gtgacttcat cgcaacgatc catcgtgatg 188580
tccctcgcag aacctaaaaa gaccaaaaaa aaatcttgga ccacagttgt cgatacttga 188640
agacaatatt ctcgtgagaa ctttgagatt cgcacttgaa acctcttagg atccacaaaa 188700
acaacaacct ctgtatggaa aatgcgctat tttatctcag cttttctccc aaacctcggt 188760
ttcttcctat tcttatgttt tccctagtat atttgcctcc ttataagaaa agaagcacaa 188820
gctcggtcgc acggattatt ccttctgcta atctattatt ttgttccttt tttttttctt 188880
tgccttcacc ctcttcactc cctgtagcaa cacagagtag tagacacaat aaatgagaag 188940
tttgcatgca tttgtcgtgt ccgtggtttg ttatggcgtg tggagtgctc gggatgggtg 189000
gacgtgggga cggattcttg aggctacaaa gatacgcgga gacgtcgtgg cgaggggatg 189060
ggtttattgg atatcggtga agcagcgtgg cggcgaaaga cgcgatccct gggctggtag 189120
atccccctac cccgtctacc agggacgttt atcctttgga cacgtaaatg tctcggccgg 189180
catccacgcg ccacgttcac cgcgttgtgc ccagcgccat gtgcgggtcg tttcggcgtg 189240
aagttggacg gcgtagtttc ggggattgtg aaccgtggct gagggtgtag atgggacagg 189300
aaaaagcgtg tgatctgacc gaggcgaagc atgtgggtgg tgcgatgcgg tggatgtggc 189360
ggggtgcggc ggtttccgac gtggagatgt ggagatgggg gtgatccgga tgcgtggcaa 189420
gaggcctcga gcttgggctt ctcccgcgga tggacgttct aactgtacac ggcggccgtg 189480
gcctccgagt aaaaaaacca ggtgctgacg ccagacagag acgccgtcct cggaatcgtg 189540
tgcgcgaaag cctgtgccgc ggcagcgtac gacgttccag tcagcgaggc cgtcgcgttg 189600
gcgcgccaac agtaaggtga cgacaggttg gcggcccatg gttccgaagc gtccccacat 189660
gcaccagcag tcggcgtcaa agtcgcttgc gctgtcggcc cagtcgccac cgccgcggcg 189720
gatttccgcg cgggggacgg ggtagccgag tgctgcgccc tcgccaatgt tgtgaagtgg 189780
atgcgtgagt tgatgttgat tctctgtggg aaaatgagcg ctgtcctgtg ggttggtgtt 189840
ggggtatgcg agtagtaggg gttgtgtttg atcgtagagg tgttggcggg cctgtgcgca 189900
agcagcgtag tctgcggcgt cgagctccat ctgtgtgcgg tgttcttcgt cggcgtgttt 189960
gtccgaggtt tggacatgcg gttgtgtgtt gctgtggtgt aagggtaacg tgtgttgggc 190020
gtctgggtga agcggcgtgg tgtgggtgct gtttgtgtct gtggctggca tgattgtgcg 190080
gcatgtgtgt gttgtagtgg gtggaggtta aataggtgag gtgggttccc tggtccgcgc 190140
cgcaaactgt ccccgtcccc aacgtaacct cccctacgcg gcgcgaacag ccccggcccc 190200
agcgcaaccc ccgtccccgg ccccaacacc gtcccgcaca ccccccgtct ccgcaacacc 190260
ccggcatcgc cggcggccag aacgctcgaa aacccccgac aagcgcagcg ccgaaacgac 190320
acaggcaagg accgtggaac gcaccggcag cgcgccgaaa caccgtcccg aagcccggtg 190380
ccgacaacaa ataccgtggg acgacacgca ccggcagtgc gcaggcagcg tcggacacaa 190440
cacgcttacg gccctcaaca ctccctcgag gacccaccac gcggccccgc accggcggtg 190500
ttttgggtgt gtcggggcgc ggccgggtgg gtgtgtgccg ggtgtgtcgc gggcgtgtgt 190560
tgggtgtgtc gggggtgtgt tggcagggtg tgtcagggtg tgtcgcgggc gtgtgccggg 190620
tgtgtcgtgc cgggtgtgtc gcgggcgtgt ggcgggtgtg ccggcggggt gtggtggcgg 190680
ggtgtgtcgg cggtgtgcgc ggcctcgggg tgtgcggctt cgcaggaacg agtgtgtggc 190740
ctcgcggccg ttatttcccc cgcggtcccc agggccgtcg tccctcgccc ccgggcgttg 190800
cttttcgtgt gtccccaggg acccatgctg ccgtcccccg ggaacttcct cttttccccg 190860
gggaatcaca cagacacaga cacgcgtctt cttttcgccg tgcgcgccgc acgtcgcttt 190920
tattcgccgt cgccgtcctc cgcaccacac gcaactagtc gccgtccaca cacgcaactc 190980
caagtttcac ccccccgcta aaaacacccc cccgcccctc gaggacccac cacgcggccc 191040
ggaatggatg tcgggcgtcc acctagatgg gtgcgcgccc gggaggcggc tgtgcgctcc 191100
agtggtacgc gcctgccgcg cgtcttcctt cgggtagctg cctttcccag tccacggcct 191160
tccagactgc gtggcgccaa ggcggcgcca gcacgcgccg tgcacgtcgc tgcctataaa 191220
agccagctgc gtgtcgcccg cggcacacgg gcgacgaagg cgtccgcgtg tctaaaccgc 191280
gtgctcgctg acgcgggttt gcttcctata tagtggacgt cggaggtgtc cggcgcccat 191340
ggcccagcgc aacggcatgt cgccgcgccc cccgcccctt ggtcgcggcc gcggggccgg 191400
agggccttcg ggggttggtt cctctcctcc ttcttcttgt gtgccgatgg gagcgccgtc 191460
aacagcgggc actggtgcga gtgctgcggc tacgacgacg ccgggccacg gcgtccaccg 191520
ggtagaaccc cgcgggccgc cgggcgcccc tccgagtagc ggcaacaata gcaacttttg 191580
gcacggcccg gagcgcctgt tgctgtctca gattccggtg gagcgccagg cgctgacgga 191640
gctggaatac caggccatgg gcgccgtgtg gcgcgcggcg tttttggcca acagcacggg 191700
ccgcgccatg cgcaagtggt cgcagcgcga cgcgggcacg ctgctgccgc tcggacggcc 191760
gtacggattc tacgcgcggg tgacgccgcg cagccagatg aacggcgtgg gcgcgacgga 191820
cctgcgtcaa ctgtcgccgc gggacgcgtg gatcgtactg gtggctaccg tggtgcacga 191880
ggtggacccc gcagccgacc cgacggtggg cgacaaggcc ggccatcccg agggtctgtg 191940
cgcgcaggac ggactgtacc tggcgctggg cgccgggttc cgcgtgttcg tgtacgacct 192000
ggcaaacaac acgctgatcc tagcggcgcg cgacgcggac gagtggtttc ggcacggcgc 192060
gggcgaggtg gtgcggctgt accgctgcaa ccggctgggc gtgggcaccc cgcgcgcgac 192120
gctgctgcct cagccggcgc tccgacagac gttgctgcgc gccgaggagg cgacggcgct 192180
cggacgggag ctgcgccggc ggtgggccgg cacgacggtg gcgctgcaga cgccgggcag 192240
gcgactgcag ccgatggtac tgctgggcgc gtggcaggag ctggcgcagt acgagccgtt 192300
cgcgtcggcg ccgcaccccg cgtcgctgct gacggccgtg cgtcggcacc tgaaccagcg 192360
tctgtgctgc ggctggctgg cgctgggcgc ggtgctgccc gcgcggtggc tgggctgcgc 192420
ggcggggccg gcgacgggga cggcggcggg gacgacgtcg ccgccagcgg cgagcggcac 192480
ggagacggag gccgccggcg gggacgcgcc gtgcgcgata gcgggagccg tggggtccgc 192540
tgtacctgtg cctccgcagc cgtacggcgc cgccggcggg ggcgcgattt gcgtgcctaa 192600
cgcggacgcg cacgcggtgg tcggggcgga cgcggcagca gcagcggcgc cgacggtgat 192660
ggtgggttcg acagcgatgg cgggtccggc ggcgtcgggg accgtgccgc gcgccatgct 192720
ggtggtgctg ctggacgagc tgggcgccgt gttcgggtac tgcccgctgg acgggcacgt 192780
gtacccgctg gcggcggagc tgtcgcactt tctgcgcgcg ggcgtgctgg gcgcgctggc 192840
gctgggacgc gagtcggcgc ccgccgccga ggccgcgcgg cggctgctgc ccgagctgga 192900
ccgcgagcag tgggagcggc cgcgctggga cgcgctgcac ctgcacccgc gcgccgcgct 192960
gtgggcgcgc gagccgcacg ggcagtggga gttcatgttt cgcgaacaac gcggtgaccc 193020
cataaatgat cccctcgcat ttcgtctttc ggacgctcga actctcggtc tcgacctcac 193080
caccgtcatg acagagcgtc aaagtcaatt gcccgaaaag tatatcggtt tctatcagat 193140
taggaaacct ccttggctca tggaacaacc tccaccccca tctcgccaaa ccaaaccgga 193200
cgctgcaacg atgcccccac cgctcagtgc tcaggcaagc gtcagctacg cgctccgata 193260
cgatgacgag tcctggcgcc cgctcagcac agttgacgac cacaaagcct ggttggatct 193320
cgacgaatca cattgggtcc tcggggacag ccgacccgac gatataaaac aacgcagact 193380
gctgaaggcc actcaacgac gaggcgccga aatcgacaga cccatgcctg tcgtgcctga 193440
agaatgttac gaccaacgct tcactaccga aggccaccag gtcatcccgt tgtgcgcgtc 193500
cgaacccgag gatgacgacg aagatcctac ctacgacgaa ttgccgtcgc gcccacccca 193560
gaaacataag ccgccagaca aacctccgcg cttatgcaaa acgggccccg gcccacctcc 193620
gctgccgcca aagcaacggc acggttccac cgacggaaaa gtttctgcgc cccgacagtc 193680
ggagcatcat aaaagacaga cccgaccgcc aaggccgcca ccgcccaaat tcggggatag 193740
aaccgcggcc catctctcgc aaaatatgcg ggacatgtac ctcgatatgt gtacatcttc 193800
gggccacagg ccacggccgc cagcacctcc gcggccgaaa aaatgtcaaa cacacgcccc 193860
tcaccacgtt catcattgaa agtctctcca gtccatatgt tgtcaggacg tgctgtcgtt 193920
ctccgcttgc tgcgaagccc gttcttccga gtcgtgtcgc tgcgtccagc gtcgcgccca 193980
agatgggaat ttgggtcttt tcacgcgtag cctcctccac cacggctgct gatcgccgtc 194040
actaaggacc gacacggagg atgacgagga gcttctcccc gactccgcgg tccgcgaccg 194100
gctacgtagc gcgtgtccct gccagtctcc gcagttacac cacacgtcgt gagcagcgtg 194160
cacctgctgc cgccactggg cctcggcgtg ctcaggccac ccgccggagc ccggtctgag 194220
ctccgacgca ggatgcgcgt actcaacgtg cgccttccag tccatacagc aacaccatag 194280
gtcgtgcgag tcgtcggcta cccgccgcca ggccagttcc cgcatgggaa ggctggacac 194340
gccgaccgag aggtcaccga gcccggacgc catctcttct tcctctccgt cgctgtcatt 194400
aagcagccag gtcacctcct ccgctccgcg gtccgccggt ctcgacggac cgcgccgccg 194460
tcggcaacac ggaaaacagc acgccagccc gagccgctaa ggccgcatgc ccctgccgcc 194520
caactgaaca cgcatacccc gctcaactgc gttttgccac ccctgtcagt gctctcgctc 194580
gagcaccacc ccgcatctcc caaccttttt ccaataaacg aaaccgacat gacacacgta 194640
atgggtactc gtggctagat ttattgaaat aaaccgcgat cccgggcgtc tcagcacacg 194700
aaaaaccgca tccacatcat agacaagtta cagtccacag tcacatacac gataaacaat 194760
accaacaggg taatgtttat ggagtaaaac actattgtcc aggccacatg cgtgtatgac 194820
ttccgcacca tcccgtactg catgttccac atgtacgcgc tagacgtgta atccactcgc 194880
agttcgggga cgcaacgcag ccagatcaca tccccttgca gtaccagacg cagggctagc 194940
gtctcgaaga tcggcatcac atctaagttc cgcacgttcc actttaacga ctccccggga 195000
acgaactcca cgtcgtcggc gtgtacgtac aggttctctc ccacgccgcc ataatcggcc 195060
ttcggatcga agacgaaccg actcatgttg cccacgatgc tcccccgagc aaacaacttg 195120
ccgttgtcaa tgtagcaccg gttgtcctcg atttgaaacc agggatgctt ggccgtggac 195180
ttccagggcc ggagcgcgtc ttccccggct ttagtgattc catcgggcag gcggatcaag 195240
ggacccatgg aggtccaaag acccacccag gctttccaga gattgttcat ggtgaaacag 195300
cgtgtggact gtacgctctt tcccaattta tatcccagag tagtgacgtg agcccagcca 195360
cctcccagat tcctgacgtt ttggttgtct ttcctgccaa ttcctcccgt aaacttatga 195420
ttatcctagc ccattcccga taaaaataca cggagacagt agatagagtt acgaataaac 195480
cggtttattt attcaagtgt ctcaggagat tattgaacga gcgtggatac cacgccgtcg 195540
tcagttcatg gtggcattga gcagccatag caccagagtc ccggcgcccg gtatcagaca 195600
cgctgaccta ccgggcgcct tcgagtccgt accccgcggc ctgggtgtta gagtccgtac 195660
cttgcagccc aggtaggttt caggtaccag ctggttcgta cctgttaaat aaatcgcaga 195720
cgggcgctca cccctacggt caggagcaca agaacaacca gagagaacag atatacgagc 195780
agggttctga acagcagacc ccaattgtcg tctctcatgc ttcgctgaag gtaccagttg 195840
atggtctgag agctatagtc catcctcacc tgaggaacac acgcggcata tttcttgggg 195900
tctccccacc tcgtagacaa cgtgatgtcc accatatcca cggtgtgcgt caccgggtgc 195960
ccaccgatgt tccactcgaa ataggctccg cgctcatcat ggtggtactg ctcaccggac 196020
acctgcagtc tgtccatgta agattgagag acgataccca cgttcacaaa gtgtttctcg 196080
gtgaagttgc ccgacatcct ccccttgaag tacagcatgc ccatatggaa ccagcattgg 196140
ttctcctcca ctcgaaagtg ggccgatctg atctccgata ccaccacatc caggggccgg 196200
ggcaccgagt ccgcgagtct caggaacaag acggccagga tcgcgagcac caacaccggc 196260
ttcatggctc cgaaggtccg ctgctcggct ccgctcaccg ctccggtctg gctgcagcag 196320
tgcttcgctg agaagtagcg tgtggactga acggtgtttt tgaatatata gcgtttcttg 196380
gtgacgttgt ttcccctacg tagtaggcaa ctacgtgcca aaagaggcgt tacggtactt 196440
tccgtactgg gatttccaaa ccgggacttt ccacacggcg gtttcaacac cgggactttt 196500
cacacggtga tttcggcacc gggactttcc gcacggcggt ttcgccaccg ctgacgttct 196560
catcgccgcc cacgtcaacg gtggcgacac cgtactttcc catgcggttt ataaacgtca 196620
agagtcacgt cagtcgccca cccccattac acggcgatat cccgataggg catgagggga 196680
cccgggtgtc gcgacatgtc gacgacaggt gcggattagt ggtcgtgtcg cgacatggac 196740
gtgcaggggg atgtctgtcg cgatagagtt gatgtgacag cccgctacac ctctctgtcg 196800
cgacatgcat acacaacggg ccggcttgtc ggcgattgtc gcgacatatc gttatcagtt 196860
agcgaccgga gttgtctatc gcgacatatc gtcgactatc gcgacagaaa aaataccgtt 196920
cgtagagaat gccgtgttga aggaacgcgc ttttattgag acgataaaac agcatcagga 196980
gccacaacgt cgaatcccac gtccagtcga ttcgtatgtt atgctgcaca gcaatgctag 197040
aataacaacc agcagggtaa tcccgcaaca taaatacaaa gtcacagcga agaatccgtg 197100
tcgttctatc aagcgaaacg cgttccaaac ggccccgtca cagacgcagt tattcataag 197160
cgttaacaac cggtggctag gatgaatatc caaatcacag ggcagtagcc gacggactcg 197220
ttgacaggtc agcctaccct caaggttcct atcgttcgga cgggatttgt gcgttttagg 197280
cctctttttc gccgcctgca agcattggtg cgcaaagtcc tcacccagct gtttccagct 197340
atcatctgca tctgtgcagt cccctgtatc gttgtaacaa acgggtctgt gcgacttcgt 197400
tctcggaaca caagcttgtt gtcgcggaga cagagagaga agggttttcg ggtcacgcga 197460
agaccgctca ccgggggtcg gcaacgcaca catcaacaga aaaccgagac gaatcaagag 197520
atccatagtg aaggagtgat atcgacgtgc ttacgaaacg gcgattatat atgttctcaa 197580
caataccgcc ctacgttgta tgatgtaacg tgtgacgtga gtctgatcca acactgaacg 197640
ctttcgtcgt gtttttcatg cagcttttac agaccatgac aagcctgacg agagcgttca 197700
tcggggcatg aagtacgcat tacacaaact ccatatattt gttacgatag aatacggaac 197760
ggaggaggct ttcgccacac ctatcctgaa agcgttgcat tctttatgat aggtgtgacg 197820
atgtctttac cattcccacg gctgctttgc gtgatgatga cattcatcat gtatttccat 197880
tcacacatac cttttgtgca tacggtttat atatgaccat ccacgcttat aacgaaccta 197940
acagtttatt agcccttgac aggataggtc aaaagattat atgtaggttt tccggtaaac 198000
cgaattgtga tatttctctg caggaaatag aacagcctgg tacctataaa acggacaatg 198060
cagtactgta gcagcgtaac caagtaggtc cacatgaaca cgtacaaaat tatggtaagc 198120
catcgttttt cataccacag cctgtagctg tcgtacatga atgaggacgg tcgaggaacc 198180
cagggtagtt gtaattgggg gcgacattcg tactgtccag aagacaattg cacgggtttc 198240
agtgagatga gtactttagc gatgtcggcg ggggcgctac gtttcaccgt gacggtgaga 198300
acttgaccgt cgttttgtat ttcatgaggc acgttataca agccactggt atcatgaagg 198360
atgacctctg atgcgatgtg aggattaaat tgtccctcaa accgccaaac gctggtcatg 198420
tttccaccgt caattacgca gctgacggtg tgagatacca cgatgttgga cttaggtttg 198480
ggggctaatt gcctttttac aaattccctt ctgtattgca ggtcctgctg ccactgcttt 198540
tccgtgcgga aagtcgccat gtcttccaca cgtgtggcga cgatagacgc caccaaggta 198600
gctaccagaa gcagctggat ccgcatggca ttaccgtatg tcaattagaa agttgagcgg 198660
acacggttat cgttcctggc ggatataagt atataaacgc gagttagcct ttcccgtccg 198720
ttttgtacac ccgttcccca cacaaatgac gaatacgacc ttttttttta taaaaataaa 198780
ccacgtgtat tatataaaaa catttacata gaaaagagac acacggatca acataaggac 198840
ttttcacact tttggggtac acaggcgtgc caccgcagat agtaagcgct ggatacacgg 198900
tacacagtcc tggccagcac gtatcccaac agcagcacca tcgccataca gatggcgatc 198960
acgaccccga gctctaagtg tctgtattca tagtgtagtc gccgcaggtt atccactgaa 199020
ttcccgtaac tgaaataacg tatatggtac cgaggctggc accacatggg tttgcatttg 199080
gtgcacggca ccaaatgcag agtgagatgg tccaagtccg tgggcaccca ctggcgcaaa 199140
cggaatacgg cttcggtggt ctccacgagg cactccgggg cgtgcagacg gccccacttt 199200
cgtccgcgac ggcccgacca gccgacccga gccactatcc ctttctcggg atagaacgta 199260
ccctgtacac gccacacagc gtccaacacg ccgtccttga cgacgcagct ggcctgatag 199320
ctggacacgt tgttaagcgg cggaaagcga aactgacgtg ccggcggagc cacatagttc 199380
ggttcaccgt gttgtcgcgg ttcgtcctcc ctatagtaat agtagtcgtc gtcctcatag 199440
gggttgccgg cgtgagccag cgttacccaa cagcagccca ggccgacgag gaggcgcagc 199500
caccgcctca tggcggcttc gccagtcaat cgtctttagc ctcttcttcc cgtgaggtcc 199560
ttccggtggc gcggtgccga cctcggaccc agggacgtat ccacctcagg tacacacagc 199620
aggctacctg gacaccgaag ctgaacaagg ctacgtgttt cacaaactgc accagtacca 199680
catagaggaa tgtcaggtag cgtctctccg caaacagccg ttccaagtct gagggcgtta 199740
cccgcagcgg caaccagggc agcctggacg ccggccggca atggagcacg ctccggttac 199800
aggcactgca ggggtaaacg gttaacatca cgtaagagag tcgtgcgtcc acctgtggga 199860
gctcagtttc gtaacgtaga gccccgtcat tttccagctg gggtgcgccg accttgaaat 199920
gggtcgcgct ccgctcgtta ccccaggtgc cgtaggctct cggggccgta tcggagaagt 199980
tgccacgcac aagccaggcg gccacgagta ccccgtgctg gacgtaacat tcggacacgg 200040
aactggagac acggtagccg gacacgtccc caaacccgcg agggtactgg ggcagacgga 200100
cggacttgct atttgacaac ggacagatac gagacgacga ggacgcagac gactcgtcgc 200160
tggaccacga caaccggagc gactccttgg agcggctcga gagtacactt actgcgatca 200220
gacaccagtg ccagaagaag gaacaggtgg acggggacca caggatcata gccgccggca 200280
ccgcggccgg ccgcaggaag ccgcccggcg cgtcgtctgt gtgcgggagc cgaaacaccg 200340
tgcctcttta tatcgtcccg acgtgacgcg agtattacgt gtcaggggaa acccccgtca 200400
cgacgaacgt gatttgtaag tgacgcgggg tgctgacggg gttcggcccg agaggtgacg 200460
gagcgcctca cgtcagtatg atgtccgatc cgcgtcagcc ccgacgtggt tgtggtcacc 200520
gaaacccacg tttatatgga cgttgagagc agcgcctgac cacatgattc atcataccat 200580
ttctcggaat cgggcccatg ccgggaaagc acattccttt tcagtaaaca acaatgacat 200640
cataacaaat cattttattc gcgaggtgga taataaccgc atatcaggag gagggatcgg 200700
gtgatgacgc aggccccgca gaacagtccg aaataaattt ttagtattgc cccatagtcg 200760
cctagatacc agaggtacgt taagttcatc aaaacgccca tcggcgtccc ggaatcgtat 200820
accgggcaca cgaagcgttc ataacaatcc cgggaggcga gtgttagggt agcagagtag 200880
tttcggggtc ggtttccttc cggcgacgac agttccgtgg gcagcagaat gtacagcgcc 200940
tcggtagctg tcgcggtgcc ttccacgagg atgggctgcc ggtgcctttc gtgattttcc 201000
ccgtcgtgta gccaagccga ggcccgcaaa gtcttaggcg aggggaattg tccatagagt 201060
ttcaccgcac ccttcagtac atggttctga ataacacagc cgcacgtgaa gtaggtaggt 201120
tctctcgtct cctccgtggc tgccgccacc actcccagcc accacaacag gcagatcgcc 201180
agagggttcc ggaggcttcc ccggcgtagc atggttttgg gttaaagcaa aaagtctggt 201240
gagtcgtttc cgagcgactc gagatgcact ccgcttcagt ctatatatca ccactggtcc 201300
gaaaacatcc agggaaaatg tcggtgcagc caacctttca catacagccc ccaaaacact 201360
tgaatcactg ccaccatcat cagcgtatac tgcgccgact taatcgtgag cgcgtagtac 201420
gccattagac ggcgatcttc gaacaatagt cgttcgatgt cctctaacga gctccacagg 201480
ggaacccaag gcacgaggca ccggggttcg cactctacat aataagtttg gcattggtgg 201540
cagggggaaa agtagaacaa cacgagtttt gtgcgttggg gaacacgata gtcccggagc 201600
cagtagcgtt ttgcgacgag gctttcggag acgtcctcca ccggcgtcgg cactcgatcc 201660
gcgtagccct ccagcgtctg gtagtacacc cggggtgtcg gcgtgggcac ggacaggttc 201720
ccgcgcaggg tccacagagc ctccagtcga ccgcccgatc ggagcacgca gcgcgcctcg 201780
gaatactcta ctcggtactc cgaaacatcg gacagaggcg gtaacggctc cgtctccacc 201840
aagggcggag gttcatcgaa aagagtcaag gataattcag gcatactacc cgcgaccggg 201900
gcccagaggg ctagaataag cattacaagg ttcattctgt cttacaaggg aaggctgtta 201960
ccctgtctag actcaaaagc tgtaaggctg tcttatagca tgtagtcttg cacgtcacgg 202020
ggaacagggt ggtgatctag tgacgtcggg agaacacggt gttttagggt gcgggggaca 202080
aaggacagta cgacagatta ggtgatagaa acgttttttt ttatttatga aaaagccagt 202140
gtgccgtgcg gcctagggcc ccggcgtagt ttggatacca gatgggggcc gtcaggggta 202200
ctaccacgag cagaaacata atgacttggt ccatgtatag cagcatagcg gtgcgcagca 202260
ggtcgccgtc cgtgtagcaa tttgacggtg agcgataaag caccgttaat gtgtcgcgga 202320
taagcacgat cttgaggccg tagatgaagc tcacagtcag tgctaaaatg atgcgttggt 202380
atggttccca ggactgcacg gcgatgaaga gccagagtat gggaagcatg aagcttagca 202440
aacagaggat ggctaaccgt cgttgcatgt tccaggccat gagccaggct aggcccgtac 202500
accagacgca gagcatggat gacaggacat aggcctggat taccacggtg cgatcgaaac 202560
acagcccgat ggtggacacg gatatcgtag tgagggtggt atataccatg accagcatca 202620
gggtcccggg tcggcgccga cgttccagcc agtacgcgtg gcaacgcaga gcgcagggta 202680
gcagtgtgct ccagaagggc aatgtatcgc gcaggtaggg ggccgtcacg cgccacggta 202740
tgagcatgaa aaggatggta gtggctatgg tggcgctggt ctggaacacg acagtgccgt 202800
agagacgtac catccagaga aagtgttgaa cgctccgcag ggtgtcttca tctttggtga 202860
ttacggtgac tcgacggatc ggcggtggtg acggcggcga cacgggtggg ggtttctctt 202920
tcttatggcc gagtggctcg ccttggtgaa actggatctg taccatgacg ggtgctcgac 202980
gaacagtcgt gggggcttta ggtacccggc aagttttata gagaaagggg gacgatgggt 203040
ggtggctacg agccaccgcc accttcgcaa tacgaggatc tgaaggcggc aaagacggtc 203100
gtccagggca ggcgccagag gttgggactg agcacgatca gcgtgatttt aaacatggtc 203160
accagtccta cgtagatcag cagcgagccg cgtaacgtct gagcagccgg cagttcgtcg 203220
cggatgtaac gcgtgccgta gaaagtcacg gtcatcataa ggaagacgat ggcgccgtag 203280
ccgtagagta gaatacgctg atgatggaac acggtctggt cgccgataac ccagagcgtg 203340
atgaaaaaaa cgctggtgag tacccgtgag catatgagct cccaacgctt agcgcgaaag 203400
ctgtccccaa ccatgacagc gccggtgcaa gctatccaca gcgtgaggac cagtgtgtag 203460
tcgatgagga tggcgggcag gtcggagcac caggtgtaga aaaccgtggt aacggagagg 203520
aggcctacgt agcccatggt caataccacg tcgtcggggt gcctttcgcc ctgtatcaag 203580
accaaacacc agagaaggga gggggcaaaa accagcagca gaggggaaga ttcatgttga 203640
catatgttgt gggaatcggg gatacccagc caaatcattc cgcagaaagc cgtactgatg 203700
gcgatgtgaa agaccactag ggcgtagacc cggacgagga cagcaaaacg gcgcagccac 203760
ataaggccgt ggtgcagctg caggagggaa gcccattgcg gcgaatgtag cgacggtagc 203820
ggcgggtcca tgaggcgggt gatgcgcccg agtgaacggg tgagcgtctc ggtggagtct 203880
tcttataaac cagcggagct caggcagcct tgctctggaa cgtcgcagtg gtggtgttga 203940
ggatgacgct gagcgtgccg ttgtcaatca ggtaatgatg ataggtgccg agcttggcca 204000
ggtagctgaa catttggtcc cagcgtgccg accacaccac gggcgtgagc atcaggagtg 204060
tggtgtgata gattagtgtt tcggtggcgt aaagtatcag cgagctgcgg atgacgtggc 204120
tcacgggcat tttggtggcg atgtagcgca cgtcttggaa aaggacggcc aggatgcagc 204180
ccacgaacac ggtgtagaga cacagcaaag tcttatgtaa ccaggtgtaa gtagaagcca 204240
ggacgctgac catcaccgtc aaaagtgtgg aggtaaaaag cgcgtcacgc cacacggagc 204300
tgagacggtg ctcccaagcc acgccgttgc aggccacgaa caacgtccac gttaggatga 204360
ggctagaaat gccgatgggc gctgtggcgc acaggttgag cccggcggtg gtgaacgaga 204420
gaagcgccac atacagcgca aacaccaggc cgttgctggg gtgtctgtga tcggtgagct 204480
ccagcgcgcc cagaaccaat actggtgtgc agctaagcaa tagcggcgag ggatcgtcgc 204540
tgcacttgta gcccagcgag gggtaaccca gccaaaccag cgcgctaatg agtacgctga 204600
aagcggtttc cagcgtcagc aatccgtaga cacgcatgac aatcgcggtc cgccgtagcc 204660
aacacacggc atcttcggaa actgtggacg ctgtttccga ataccgggag gagatcgtgc 204720
ttccctcttc caaggatcgg aaagtagcgt ccgtcgtttc cgcggacgcg gcttccctgg 204780
tacgctccgt ttccgacgac gcggtttccc gctgcgtgga aactgtctcc atgtcgggac 204840
cgcagcgccc ggcggcgtat ccgcaaggtc tcgaagctac agcttgtcag aggaaaagta 204900
ggtttgcaaa aaggtgcgca gggtcatgat tctcagcacc atcagcagag tgaaaaccag 204960
actgagaaac accttgacgg ccgccaaaag cgcgcgttcc agcggcgtct cgtagcgtac 205020
agccagggcc gcttcgtgga aatgcgagac ggctagacag gtaatgagca cgctgaagga 205080
caagacgatc ttaaagcacc aggaccaacc acgcctcaag atgaccacca cgattgccgt 205140
gaaggtcaac gtgatcaaag catggacgac cacgatctga cggcggacgg tacgttcggg 205200
agccaacaac gctacgccgg tgcagctgag aaaggccagt aaggtgaaca acgcggccga 205260
gatgaccaac gtaccgtcca ggcagagaca tatcacgatc aacggcggca cgtgaagcag 205320
cgtgtaaaag agcagaacgc cgatattgct gggatgcgat gtttcgtaac agtgaatgaa 205380
gatcactgac gtgacgggta tgacaaagac gaggctgggc gaggactccg tgagacacag 205440
acgagaatgg tgaaaccacg tcgcgggcgc cgcgtagcag aaggcgctca acaacgcggt 205500
caagccggcc agctgccaac ccacggcgcc ataggtgtgc agcgccacgc ggcaacagtc 205560
gacccaagcc agactgcggg tcgccagccg ggtctcttgg atcccggggg gcacgtagat 205620
gaccgtgcca tcggtgggta cttgaaaccc tttttctctt ctcatggtgc gctgcgttct 205680
ctggaaacgg ctgctctgtc cgaaaaccag ttccgaacga aaatctaggg cgagagggtg 205740
gacaacggcg tcgacgacga agcatgggac aggtcgttcg gcgttaacgt catcgcgtcg 205800
gacgacggta gttctaagag acgtagatcg ctcagcaggt cctgacagtt gcggattcgc 205860
aagatcagaa aaaaaaggga aatgaacgta ataaagagct gtagcgacgt atgcgccaca 205920
tcgcgtggca taagaacgtg acggacgaaa aggacctgct gcgaaaagtg accggcgaag 205980
ataaggccca ccgtgctgta gaagcccaaa agcagccgca ggggccaagt ccagggccgc 206040
gtgaagacga tgagaacgtt gaccagaaag accacgaccc agacgccgtt gatgagggta 206100
aattgatcgg acagggtgca gttgtcgcga cagatgaaga ctacttccgc gcagagcaag 206160
gtgatgacca acgtgagcac aaacgacgtc aacacctcgc ggggctcctg gcaggcacac 206220
gtgacaccta gcgccgggat gtgcgccagg aggccggcga gtaatagcac cagctgtcgg 206280
aacggacgac ggcagcgcgg gtgccggttt cgctgagcga gaaccggtcg ctcatagcgg 206340
aaatacacga agagcgcgga ggccacaggc accaggagga gcacctcggg cgcccagaca 206400
acgtgacaag gaaagcccgg acgcgacttg agagtcgctg tagggaagac cagagagaag 206460
ctacccaaga cggccaccgc cgcggagatt tggaagagga gcaagccggc gattcggacg 206520
acaacctcga agcgatgcac ccagcccagc acggccacca cggccgcttc atcatagtcg 206580
tcgttgttgc cgctgtcgaa cagccgccga aacacgatct gtcgctgggt cgcggtggga 206640
aagcgcagac ccatgacagc cggaggctat atgaccgcgc gtctaagacg cgagatccgt 206700
ggggggactt ttagatgttt gggcggcccg cggttctaac aggcttgatt ggtggagacg 206760
gccggcgcgg cgggtggggg aaacgacgag tttttccgtt acgccatggt tcgcgtgagg 206820
tttctctgta cctcccgcaa aaggtcacag cccgaaatgg aggccgcgtt ggtggccccg 206880
gtggcgcgtg acgataacca ggtcatccaa gcgatgagtt tgtctaatga gtcctcggtg 206940
gtgaagagga tgagaatgag caggtacagg tacaccaggt tctcatagag acacaaggtg 207000
agcaggtcag cctcggacca cgcgatctca aacaggcgcg tggtgtcaaa gaccgtgacg 207060
accagcatga agctgagcgc catggcgtaa tagcccaaaa aaagtttgtg ccccaacggt 207120
acgggctgca ggtaaagtgc gatcaagaac gcgataacgc cgatcacaaa cagcgtgacg 207180
atgacctgcc atcgacggtg attatggccg gctagacccg tgacgcagct gcagaggcta 207240
aaaagcacgc aagccaagag gcccgagaag gtcactagcg tagaggagga gcaggcgctg 207300
gccacgatca ccgaaagcgt cgtgagcacg ctataaatgg tgagcaggcc agggctcggt 207360
ggcgacgtga acgatccttc atcgcgtttg ccgtgcagca gggccaaaca gatggtgggc 207420
accatcaaac ttaagggcgg cataaagccg gtgcaacaga gaaagacggt gcctttaaga 207480
tgcggaaaag ccagcaccag gcccagacag agcaagaagg tgcaggtgcc ctgcacggcc 207540
acggtgctgt agacccgcat acaaagtaaa aagcgacgta cgtcgttcgt cgacacggag 207600
gaaatcataa tgactccgcg cgagggtcgc gggggtgggg gcgcccaggc cgtcccggtg 207660
gcctctgagt tcggagacat gacggcggtg gcgatcaaaa ggcgcgtatg agaaaccgtt 207720
tatagagtgt aatagaatca ccgtcattcc cacacggcgt tcccccataa agtcacgtaa 207780
cactcgagta agcgtgaaaa agctttattg ttgaataaaa aacacgagta caacaccgag 207840
ttgcggtgtc ctgtctgtct actgggtggg gaaggttcat cgtctgtctc tagagggaag 207900
gtggggaatg tctaagcgag cgggagcgtg tcatctcccc catcttttta caacaagctg 207960
aggagactca cgccgtcgat gcgtccgccg tgtttctcgg cgtactgctg cacccagacg 208020
tggccgctaa atatggcgac gctcatgttt aggagactca tgacgatggt gtacaacacg 208080
acgctgacac agacgctgtt tttagacaac gttccacgct ggtagatgag atccagggtc 208140
tcgtaaataa gcacggccga agcggcggtc accaccagga cgtagagtcc gctgtagatc 208200
ttgctgaccc acagcacggg cgaaaagtaa agcaataggt aaaagacgat gacggaccag 208260
ccgtagccaa tcccgatgac tttccagcgc gtgggattgt tgccggccag gtaggtgaga 208320
ccgctgcaga gaacgaaaaa gaccatcacc agggcaaacg acagaccgat gacgcgcctt 208380
tctccgcaaa agcccgtgca cacggtgatg ccggtgttga tcagcaagca cgccaccgtg 208440
agatgagcaa aattggtggt gtgtgggcga aactcggcga aaccgcgtag catagccagc 208500
gtggacacgg gtacgatgga ggatagggct ggcactatgc cgttggcgca ctgtccctgc 208560
acatcgggga aggcgagcca agccagcaag cagaccgtga gggtacaagc cagctgccac 208620
acgagcccgt gatagacctc catgagcagc ttaaagcgtt tcaaccattg gaagagctgc 208680
tgttcggcca ccagcgcgtg gctgcgatgg agcggcacga tggtgaccgt cggcgactca 208740
tggtgttcgg aaaccgaggc ggtgtcgccc atgctgccgc ttacgaccgc tgtcggtcta 208800
aggtaggcgt cgatgaaaca gtccgtctta tcagcacccg gttaccgcgg atttgattga 208860
cgtcacgagt gtggtcaaac cgtggcggca ccctgtatcc gacccgtcgt catgggctcc 208920
acaaccagag cctcagaaga tggtacatgc cgatgaataa agccacattt tcgacataga 208980
ggcgtagcga gggctgaaaa ctctccggga aagaactctg acaggtgatc agggacagat 209040
cgtgaattag catcagcgtc accgtcaaca gcgtcgtcgc gtgtaaaccg agaaagaacg 209100
gggccgcggc ccgcagcagc caaagtccca gcgccgtagc gcagagcaga gacaggaccg 209160
acggtagcca cagccgccgg agagacgcgc caggatcgca acccaaaagc gaggccccca 209220
ggcagctgag atctaccgcc agggcgagaa gagccgcgcc gacaaaggcc tgcggcgacg 209280
gctggcacat cagcaaggtc agaaaggcta gcgcgtgcgg caggcagtaa gccaacagga 209340
gtgggagttt gcggggacaa cggtcgatcg acggaccgcg tagcagcagg aacaggcagc 209400
cgacgggcac gacgaggctg agatgagaaa gcggcggtgg gtcgtcgtcc cgtccccgct 209460
cgcatagctc ggccaccggt ggcggcatga gccaccagct gagcacgctg agggcgacgg 209520
tggcggtaag ctggaaggcg acgaggacgg aggcgcgcag ccataccgcc agcctctcta 209580
ggtaggggac tacctcctcg acggtccatt ctagcgggac gacatgaagc atggcgacaa 209640
gcgcggctgc tgtgaaaacg ggcacggttt tataggcatt aggacttccc cgtcgtactg 209700
gcggctgtca aagtcccgtt gtccaaaggc gcgccgtccg aaagactaat ccaacgggga 209760
cccgagagca tgagcaacaa cgtgagaaag atggccatgc tgtccaggta gagacagacg 209820
gcgtgacgga tgcattggtt aggtgggcag aaaaagatga ccataagact gtcgtaggcc 209880
agaataccca aaaagaagct gatagagaag gcgcacaacg tcaccactat cttctgcagc 209940
caatcggcgt cgcttagcag agcgagcgtg aggaacgaaa gcagcattac cacgtagacg 210000
cagctgatgc atttccagcg acgtcggtca cggccaccta gaaacgccag ccccgtaaag 210060
gagataaaca acgccagggt catcacgtag gaacctacta gtacgcggct ttcagagcac 210120
atttggaaga tggccgccgt caggctgttg gccaacagat agatgaaaag caccgtggcg 210180
ttactagggt gttcgttgcc caacgtgtac gtgatgaaca tgcagacgat gggcacgagc 210240
acggtgagaa agaagctgta gttctcgacg caaaagttgc ggttttgtgg gaaccccaac 210300
caaaaaacgc ttcccaagcc gaagctgaaa gccagctgaa agatgaagat ggcgtacacg 210360
cgcagccata cggtgaactt tttgaaccac tcgagagcct ccatgcggga gagcagcagc 210420
gcgttagcct cctgcgcctg catggtggcg acggtctcgg cacaaagccg ctgcggcgca 210480
cctacccttc tcttatacac aagcgagcga gtggggcacg gtgacgtggt cacgccgcgg 210540
acacgtcgat taggagacga actggggcga cgccgctgct gtggcagcga ccgtcgtctg 210600
agcagtgtgg gcgctgccgg gctcggaggg catgaagtag agcacggaga caaagaggta 210660
catgaggtcc atgtacaagc agagcgcgcc cgggatataa ctctcatact cgatgtcgtg 210720
caggatgtcc tgcgtatcgc acaccaccga ggtcacgatg acggccaaac cggctatcat 210780
caccaggatc tcacttaccg cctcgggaaa aagagaaaat acggcgaaca gtaagagaat 210840
cagcgtggat gcgcccgtca atagggaacg ctgtaattcc acgtcgcggg caaacagata 210900
cgtagcgagc gtgaggaaac aaaatagcgt cactgtggcc accatggcat aaatgactga 210960
acgatgacta aagtggaagc ctgacgccgt gacagccacg ctggtaagca acgtgtacgt 211020
cagtaagatc catacgtttt tgggaaagtt gggctcggcc caacgcaaca gacctaggca 211080
cacgatggag atcattaagc aagacagcgt cagacgcacg ctggaaaaga gctgctccaa 211140
ccggtgcggc aacaccagcc agcaaaaggc gcagacgctc ataaggatga ggcattgcac 211200
ccagataagg atgtagatgc gcagcaggaa gaccgaccgg gctatctgga cctgaccgcg 211260
gagcgacatg gcggcaacgc cggcggttat cgccgagatt cgtctaaata cacgaagcga 211320
actagaaaac gcacacacgt gatttgcaaa aagaaagcag ctgccggctt attattttat 211380
taaaaattta tctgtgcaga atcataagtt tatgatgaat aaaaacgggg aaagggaatc 211440
tgcttttagg gacccgggtc tggtccgtcg tctcccatct ggtcgggttc ggggatgggg 211500
acctgtttca gcgtgtgtcc gcgggcgtgc atggcttttg ctcgccggcc gcgctgtaac 211560
caggcctctt tctctgtggt cggcgagtct tccgacgggt agggagcctg ggagtccatc 211620
gcttcaggcc caccgctcgt tccctcgacc gtcgtgtcgt cctcgttttc gctattacac 211680
ggggtttctg gagtatcgcc tatacggttg gcgattctcc gggggcggcc gctctcgtcc 211740
tcgtcgctgc tatcgccgcc cggtaattcg acgccgcatt cgttgtacgg aacgcggcac 211800
atgggcggcg gaaagaactt gggcatgcga aagcagcgtt gtccatccac ggtctgcgtg 211860
gtttcatcgt tatcctccca taatcccccc tgtagcgccg gcagcgtttc gacgctgtga 211920
gaggggaagg cccagttctg gttgtcttgc agcgcgcccg tgggcagtag gtccgtgcgg 211980
ccccatgcgc tgctgttgtt gggtaccttg tcagtgccgc gagtaggtcg cagaaaccag 212040
tccagagcgc tctctagctg cgagcgtgtg atggtgccca gtgcgccgtg ccagcgcagc 212100
acgtctcttt tcagcgtgtg gtgacagacg ggcagctcct ccaaccgaca ctcgccgcgc 212160
aatccgcggt cgaagcggca gagaccacgc agtttaagca gaccgcactt gagaaacatg 212220
tgaaaattat cggcaatgcg atataggtcc gagtcctcga tcttgtgtag gtagaccacg 212280
ccaaacttgt cgagcagcac caggccgctg ggcacaaaag gcccgtaggc caggtaatag 212340
cccacgaggc cgacgacgta ccactcgcag cacaagcgtt gacgaataaa gttcagaaga 212400
tcgcgaaagt ccgcggccgg catgtggtca aaaggccggc aggcgcgcag gccctcgatg 212460
gagcccagca tgagcaacgg ctccacctcg gtgcgacccg gcgtgcggat gaccaggttg 212520
agaccgctca tttcgcgggc cgtcttggcc acggccgcag cgtcagtggg gtcggtgcag 212580
aggaattttt gcacatgata gcgcggttcg gtggtggcga acggcgtttg tgggtgccga 212640
tacacatatt cgcaccagag taggccgttc ttggaaaagg ctttgatatc actggccacc 212700
tcgtagagcc cgtcggtctc ccagtcgtag acgtagacgg tgccgtaatg acttagcatg 212760
agcacgcagg gcagttcctg cgcctgcttg gtgtttcgtg ttagatcgct gtcgggtgga 212820
cgcacggcta gtacaccgac ggcttccagg gtgtcatcgc agcagagata gtcggcggcc 212880
agagaacgtg cgtaaatctg cgggatggcg gcctgttcgc gcatcactag gaaccagttg 212940
gcggggttgc gcagtgctac ggtggttcct tggtggcgtt gcacgtaggt tctcagcgcc 213000
ggaggatcgt actggcgcag atagaggcct tgcagcatcg ataacgtctt ttgaaagacg 213060
gtgtttctaa attgaaaaac gccgtagtcg cagcggatag catcttcgca gcgctcgtcg 213120
cgctgtcgga gataggtgcc ccaggcttcg gcggcggctt tggtgagtag ggacatgccg 213180
gcggagccgt ctcgacagcg agtcggataa agcgcgctgc gcgaaagctt aatataggag 213240
cagcgtcaga cgaatcgcgg ctggtggccc ggggggtggg acgcgccgcc tacacaaagt 213300
gctcccgaaa atcgaaactc ttgacccact ccggagacaa atccgtattc agattgatgc 213360
gtcgagcttc cacttcggct tccgaaacct cggcctccgt ccggtaggcg ttaacaatac 213420
gctgacccag gtgccaacgc tctttctctg ccaaacgccg ttgctcaaac cattcgtcta 213480
cgtccttgag gtcaaagaca gtgtcctcct caaggtcaaa gcctaggtct tcccactcgt 213540
cgtcatcgct ctcgtggccg gcggccatac gcgcggcaac cgcgtcttcc cctcctcttc 213600
tttcaacgtt gggtaccacg ttgttttctt cgggttccat aggttctgcg ccgctgtcgt 213660
catcatcctc tccctgctcc tcatcgtccg ccaaggcgtc gtggattacc tccaggttct 213720
gattgtcggg tacgacgtgg ttatcttcgt cgtcgtcgcg tggcatgggc ggcggccgac 213780
ggcggacgac cggcatggcg cggccgtcgt ttccttcgtc ttcctcttca ccgtctccca 213840
aggaacgcgg tcgacgacgt tccgcgaagt cgccgcggac cacgcgcgcc tgccaaatgg 213900
taaacgcgtc ccaaccgtcc cagttattga gcatttcggc gcgaaaacgg tcgcctcgac 213960
agagccagcg aaactgccgc gcgtagtcgc ggtctacgcc gctgtcgaac atggtaaagt 214020
gcagacgcgc cgcctcgccc atgtgtacgc agcctccgtt gcgttccagc ctggccgcgc 214080
gccgtagacc gtgttcgtag cggcgacgca cgtacacctt catgaggccg gcgcgaaaaa 214140
gttcctctag gctgtcggcc agccggtaga tttcaccggc tagacgctgc aggggcggcg 214200
agcggtccag atgcgacttg acaatcacca cgtaaaaacg acagaaacgg tcgaagatga 214260
tgaggaagga cgtgtcaaaa aaaccaccgg cgcggtaaga gcccacggca cccagcaggt 214320
accagcggca acgcagttgc agcgtgacgt acatttcgca ctcggccaag cgggcggctg 214380
gcgctacctc gaagggccag cagtccgtca agcagccgaa actggtcagg agtttcaacg 214440
ttttggcatg gcgtccaggt gtatgaaagt tcacgtcgcg tccgtggtgt tcgccaacgc 214500
aggcggccaa cgcgtcggcg tcatgaccgt gacgcagcag catcgctacc acgtcgtgcg 214560
gtacccgcgt agcaaatggc gtctgtggct gacggtatac ggcttcggtg tacatcatac 214620
cgtaacgcgc cagctcgtcc agatgacgcg cgcacagcag cagaatctct tgcgagggtt 214680
cgtagatgta gaggcgcgta ccgccaccca tgcagagcac cagctccgtc tcttcgtagt 214740
gatcttccac catgatcacg cacttgccta gcacgataag gcgttcgggg caacaaatca 214800
cgtcgtccag cagctggtcg cgtagctccg gcatggtgct gccgggccgt acctgcagga 214860
accagttgtg cggaatgccg agcgacagca cctggtcgac gtggttacgg acccagtcgc 214920
gaagcacgtc ggcgctgtac tggcactcga agatgccctg aaagtcgccc atgacccgca 214980
gaaaagtttc gtagcgcgtg tggcaataga ggaattcatc gtttcgcgta aacgtgggag 215040
ctccgtcttc ccaacgtgta cgccacatgt caaaagaggc cgccagctag acaccccaga 215100
aaagaagcag agaaagagac ttctttgtgc gacacgtttt attctgcgtc ctccgctcga 215160
cgttcaaatc tggatgtact cgcgcacacc cgtcaggctc tttaagggaa aagggtccga 215220
gtacgtcact aaccgcgact gatgcaccag ggcggtaatc acccgctccg cgccctcgcg 215280
cgtcgacgaa cgcgtcgtca ccaggcaatg cagccgcggg cccgtatcgt cctgatgacc 215340
agcggcctcg cgctcggctg cttccacacc gacaatgtcg ggatccaaca cgtagctctg 215400
cgagttggtg tcgtagcggt gtagcaccaa cgtgttgggg tccagacgct cccacgcgcc 215460
ctcgtgcggg tcaaaacgct ccgttaaaca gagccagtca tactgctgct gcagaatacg 215520
ccgctcgcgc tcgcgtcgct catcgggcaa cgcggcgtct tcgttgaaga gaatgtcccg 215580
cttgtggtct acggcacgct cgtggtggtg cgggcacagg tgacggtgtt ccatacgcgt 215640
ctgacgttga cgctcgcgct caaaacgccg gtgtcgaaag accattttca gcaaccccat 215700
gcggaaaaac tccgtgatgg tgttggcaac gcgccgcaca tagtggttgg ggtcgtccat 215760
ctggatggcg tacacggcac cgaaccagtc cagcagtacc agcacttcgg ccacaaaact 215820
gcgtcccggt cgcggacgtc ccgtcacgcc tagcacatac cacggcgtgg ccagattagc 215880
acggacagcc caccaccaac gacggctctc cacctcggtg agcgcacaaa agggccaaat 215940
gcggtgtaac tgctgtaccg ttttcatcaa ccgcataatc accgtaccgt aacccggtgt 216000
atgcaacttt acgtcgcaac ccaggattcg ttcggccgtg gcgtacgagc cctcgggcgt 216060
ggtgtcattg agaaacaaaa catgcatggt acgcgcgccc ttaggatatc gtcgcggaac 216120
gggtaccgtc attctccgca gagtggtgtg aatcacgtcg cgatacgcaa tctccgaacg 216180
tgacacaccg taacgtgcca gttcgtccag gttgtgcgat accaacacca tgtacttttc 216240
acgagtgtcg taggcgtaga cgcgagaaaa gcgacccata aaaaccacgt acggagtagc 216300
caccatgcca tcatggtgat cgcgacgtgg ctcgggcaac aaaataacag cgtatcccaa 216360
cggcgtcaac ggctcgcggc aacagatgag ctttgacgcc gcctgtttgg cggcggtaat 216420
gatcccgtcc tccgtacgta acatcacatg ccagcccttg gggggaccca aggacagaca 216480
gcgtccctcg ttacgatgaa cgtaacgcgt gatttccatt ggctccaggc aaaagaacag 216540
ttccttaaaa tcccgcaaca cttgtcggta taacgccatg ggatcctcgg ccgccacagg 216600
cagcgcgggg agctccggcg gcataactgc agcgccgtca gggccagaac ccgcagccgg 216660
atccatcatt gagcgacact ctcagccgga caaccggcgt cactgacaga agccgagcca 216720
aatacagaga aagcaacgct acaccgtcac cccgctccca agcgccgcgg aaagtgctcc 216780
gatttttcac cgtcgttcgc gacgttgatt tgcctcggtc tgagaaccga cctagcgttc 216840
ggaccggtgc gcagaaacag ccggcggtcc gagccactga gcggttcaca gccccggccg 216900
ccgatagtta ccggagagac gttcgagctg caggtacatc agcgcttccc gcttcgccac 216960
cccgcgcccg ccccagttta tactctccga cgccccgtcc aacgcgcctg tggagggcca 217020
atcggaccgc gggagctctc caagtggatg acaggcacag ccgagtgccc gaccgtgaag 217080
agccctcatc cacctgaaca gaccgctaac cgaaggaccc cgagtcgcgt ccgtcggtcc 217140
cgacgtccgt cgccatctgg ctccctgctg ttggctacct ctcggatttc aaaaaagagc 217200
acgtgccgat gacggtgcac aggaaagagc caaagtgtca cggcgtcttt ttttatttgt 217260
attcctttcc tgttttgtac tcgtaaactg ttgatgttgt ttttacatcc aaaagggcaa 217320
gtaagaaaca ggatgaggca tggtaggttt gggcgtgggg cggccctcca gcacggcggc 217380
ccgggccgcc cggcgggtga gcacccggcg ttgcgccgtg tctatcttgt gtttcttctg 217440
tgtctttttc ctatcttgtt ccgcgacggc ctctttcatc acgttcagca tgcgttcctc 217500
gacgccctcc agggatcctg gggaggaggg agtcctagtg aggcttccaa tgttgttttg 217560
tggattttcg gtttcctttt cttggtcgtc atcgtcggac gtgtcgtctt cctcttgatc 217620
ctcttcttcg tccgagtagt agacgcatag tccttggttc atcaggctgg gattcatcag 217680
gttctgacgg ggaatccgct gttgtagacg tttaaccgcc cgttccaggc gagagctcat 217740
gccgcaccag acgctgtaac gccgcacggg cccgtagcgg gctgtttgtt cgcgtacatg 217800
atcgttgagc tcttgccaat attgtttggc acactccaga tcggaggttt gtggatagtc 217860
gggtcggatc cgcggatccc aactgacatc ggcggtgccg gagacttcgt ccagactgtt 217920
acgcatagag caccagtcgg gtcggacgat aaacctgtcc ttgcggatta accatttata 217980
acgtagttcg tgatggcgtg tagaggcccg tacacgctcc acggtcccaa agcggtccca 218040
gaagggaaag ttttcgtggg ggcagcgacc cggcacttcc agacgttcgg cgtcgtccac 218100
ggcgtagtga aaacgccggc cggcctggta aattttgagc agacccactg ttaacaacat 218160
atccacgctg tcagccaacc gccagatctc gcggcgagac acgtcaaaat agaaaaattc 218220
gcaggctcgg tcgaccagga tcacgaaatc ggcgtgaaag acgccggagg gtagcgattc 218280
gcccaccaca cccattatca tggtttcaca gcataagcgg tccacaaaga acttcaacag 218340
gtcgttgaat tgctccgtct ccatacagat gaagggccag acgcctttga ggttctcggc 218400
ctggccgcag agcagtagcg gacgtgtcat ctcgcccgga gtgcgcagag gcacgcattc 218460
gccgcgataa cgacaggtca cacgctgtag ttcgctgatg ctgttgtcgt gcaggcgaag 218520
gtcgcagata atatgatccg gttgcgtggt tagcagcggc gtgcgcattt gctcgccgta 218580
gatggcctcg cagtgcaaca gcccgtgtcg cgcaaaatcg tccaaactgt gcgccaggta 218640
gtaaagcacc ccgcgatcgc ggtctagaca ccacacggtt tcgtaacgtc ctaacaggag 218700
caccagacgg gcctggctag gtggctcaat ttcctctaca tacacgaaaa agtcgtcatc 218760
gtccgagtcc tcgtcctcag aagaggaccg cggcccgtgt actctgggca acacggtggt 218820
agagaactgc aggacgccca gagactcgag cgattcttcg cagcagatga gctgacccca 218880
gggcgtttcg ggcccgtcgg tgacagccgc gctgccaaag atgtcctcaa actctacaaa 218940
atctagacgc catccgggtg gcgctgaaat gggaaggcta atgttcatat cagcatagct 219000
acgaactaag tggcggatgt cctgccgcaa gtcttggcag agaatgagct ttcgtaaacc 219060
cttgagggtc ctccgaacaa cggccccaga cgcgtagcga taggactggc gcatggtgcc 219120
gcggcgtgga gcggcacttg gcagcctatt ttatggagtt tcttcagtga cgtggcttgt 219180
tcacgtcgtt cgtgggctgc ggttggcagc tccggtctgt aaaccacccg aaaagactga 219240
catcgacgtc aaagactcac gtaatttgga acatgtgcga ccgcaaagtg cgtcagaata 219300
gcacgtggct ttaggacata aaaagtaccg tgaggtctag acgtgggttt tgtgattgac 219360
acttacacca ggtaagccaa gggacggtga aactgtatgt gaggaatctg ggtgcttaga 219420
cgactaacgt gtaatgcttt ttacaggact gttcgacagg tgatagtacc tgtaaggtga 219480
tgaccacctc tacaaataat caaaccttaa cgcaggtgag caacatgaca aaccacacct 219540
taaacagcac cgaaatttat cagttgttcg agtacactcg gttgggggta tggttgatgt 219600
gcatcgtggg cacgtttctg aacgtgctgg tgattaccac catcctgtac taccgtcgta 219660
agaaaaaatc tccgagcgat acctacatct gcaacctggc tgtagccgat ctgttgattg 219720
tcgtcggcct gccgtttttt ctagaatatg ccaagcatca ccctaaactc agccgagagg 219780
tggtttgttc gggactcaac gcttgtttct acatctgtct ttttgccggc gtttgttttc 219840
tcatcaacct gtcgatggat cgctactgcg tcatcgtttg gggtgtagaa ttgaaccgcg 219900
tgcgaaataa caagcgggcc acctgttggg tggtgatttt ttggatacta gccgtgctca 219960
tggggatgcc acattacctg atgtacagcc ataccaacaa cgagtgtgtt ggtgaattcg 220020
ctaacgagac gtcgggttgg ttccccgtgt ttttgaacac caaagttaac atttgcggct 220080
acctggcgcc catcgcgctg atggcgtaca cgtacaaccg tatggtgcgg tttatcatta 220140
actacgttgg taaatggcac atgcagacgc tccacgttct tttggttgtg gttgtgtctt 220200
ttgccagctt ttggtttcct ttcaacctgg cgctattttt agaatccatc cgtcttctgg 220260
cgggagtgta caatgacaca cttcaaaacg ttattatctt ctgtctatac gtcggtcagt 220320
ttttggccta cgttcgcgct tgtctgaatc ctgggatcta catcctagta ggcactcaaa 220380
tgaggaagga catgtggaca accctaaggg tattcgcctg ttgctgcgtg aagcaggaga 220440
taccttacca ggacattgat attgagctac aaaaggacat acaaagaagg gccaaacaca 220500
ccaaacgtac ccattatgac agaaaaaatg cacctatgga gtccggggag gaggaatttc 220560
tgttgtaatt cgatcctctc tcacgcgtcc gccgcacatc tatttttgct aattgcacgt 220620
ttcttcgtgg tcacgtcggc tcgaagaggt tggtgtgaaa acgtcatctc gccgacgtgg 220680
tgaaccgctc atatagacca aaccggacgc tgcctcagtc tctcggtgcg tggaccagac 220740
ggcgtccatg caccgagggc agaactggtg ctatcatgac accgacgacg acgaccgcgg 220800
aactcacgac ggagtttgac tacgatgaag acgcgactcc ttgtgttttc accgacgtgc 220860
ttaatcagtc aaagccagtt acgttgtttc tgtacggcgt tgtctttctc ttcggttcca 220920
tcggcaactt cttggtgatc ttcaccatca cctggcgacg tcggattcaa tgctccggcg 220980
atgtttactt tatcaacctc gcggccgccg atttgctttt cgtttgtaca ctacctctgt 221040
ggatgcaata cctcctagat cacaactccc tagccagcgt gccgtgtacg ttactcactg 221100
cctgtttcta cgtggctatg tttgccagtt tgtgttttat cacggagatt gcactcgatc 221160
gctactacgc tattgtttac atgagatatc ggcctgtaaa acaggcctgc cttttcagta 221220
ttttttggtg gatctttgcc gtgatcatcg ccattccaca ctttatggtg gtgaccaaaa 221280
aagacaatca atgtatgacc gactacgact acttagaggt cagttacccg atcatcctca 221340
acgtagaact catgcttggt gctttcgtga tcccgctcag tgttatcagc tactgctact 221400
accgcatttc cagaatcgtt gcggtgtctc agtcgcgcca caaaggtcgc attgtacggg 221460
tacttatagc ggtcgtgctt gtctttatca tcttttggct gccgtaccac ctaacgctgt 221520
ttgtggacac gttaaaactc ctcaaatgga tctccagcag ctgcgagttc gaaagatcgc 221580
tcaaacgtgc gctcatcttg accgagtcgc tcgccttttg tcactgttgt ctcaatccgc 221640
tgctgtacgt cttcgtgggc accaagtttc ggcaagaact acactgtctg ctggccgagt 221700
ttcgccagcg actcttttcc cgcgatgtat cctggtacca cagcatgagc ttttcgcgtc 221760
ggagctcgcc gagtcgaaga gagacatctt ccgacacgct gtccgacgag gtgtgtcgcg 221820
tctcacaaat tataccgtaa tataacttcg tatagcatac attatacgaa gttattaaaa 221880
aagcgctacc tcggcctttt catacaaacc ccgtgtccgc ccctcttttc cccgtgcccg 221940
atatacacga tattaaaccc acgaccattt ccgtgcgatt agcgaaccgg aaaagtttat 222000
ggggaaaaag acgtaggaaa ggatcatgta gaaaaacatg cggtgtttcc gatggtggct 222060
ctacagtggg tggtggtggc tcacgtttgg atgtgctcgg accgtgacgg tgggtttcgt 222120
cgcgcccacg gtccgggcac aatcaaccgt ggtccgctct gagccggctc cgccgtcgga 222180
aacccgacga gacaacaatg acacgtctta cttcagcagc acctctttcc attcttccgt 222240
gtcccctgcc acctcagtgg accgtcaatt tcgacggacc acgtacgacc gttgggacgg 222300
tcgacgttgg ctgcgcaccc gctacgggaa cgccagcgcc tgcgtgacgg gcacccaatg 222360
gagcaccaac ttttttttct ctcagtgtga gcactaccct agtttcgtga aactcaacgg 222420
ggtgcagcgc tggacacctg ttcggagacc tatgggcgag gttgcctact acgggggttg 222480
ttgtatggtg ggcgggggta atcgtgcgta cgtgatactc gtgagcggtt acgggaccgc 222540
cagctacggc aacgctttac gcgtgaattt tgggcgcggc aactgcacgg cgccgaaacg 222600
cacctaccct cggcgcttgg aactgcacga tggccgcaca gaccctagcc gttgcgatcc 222660
ctaccaagtg tatttctacg gtctgcagtg tcctgagcaa ctggttatca ccgcccacgg 222720
cggcgtgggt atgcgccgct gtcctaccgg ctctcgtccc accccgtccc ggccccaccg 222780
gcatgacttg gagaacgagc tacatggtct gtgtgtggat cttctggtgt gcgtcctttt 222840
attagctctg ctgctgttgg agctcgttcc catggaagcc gtgcgtcacc cgctgctttt 222900
ctggcgacgc gtggcgttat cgccgtccac ttccaaggtg gatcgcgccg tcaagctgtg 222960
tcttcggcgc atgtttggtc tgccgccgcc accgtcagtc gcaccacctg gggaaaagaa 223020
ggagctaccg gctcaggcgg ccttgtcgcc gccactgacc acctggtcac taccgccgtt 223080
tccgtccacg cggatacctg acagtccgcc gccaccgtac cagcttcgtc acgccacgtc 223140
actagtgacg gtacccacgc tgctgttata tacgtcatcc gacatcggtg acacagcttc 223200
agaaacaacg tgtgtggcgc acgctactta tggggaaccc ccggagcccg ctcgatcgac 223260
ggctacggtt caggaatgta ccgttcttac cgccccgaat tgcggcatcg tcaacaacga 223320
cggcgcggtc tctgaaggcc aagaccatgg agatgcggtt caccatagcc tggatgtggt 223380
ttcccagtgt gctgctgata ctggggttgt tgacacctcc gagtaacggg tgcaccgtcg 223440
atgttggacg aaacgtatcc attggagaac agtgccgcct tcgaaacggt gcgacgttct 223500
ccaagggaga catcgaaggt aacttcagtg ggcccgtcgt cgtggagttg gactacgaag 223560
atatcgatat tactggcgaa cggcagcgac ttcggttcca tctcagcgga ctcgggtgtc 223620
ctacaaagga aaatataaga aaagacaatg aaagcgacgt caacggtgga attcgctggg 223680
ctctatatat acaaaccggc gacgccaagt acggtattcg taaccagcat ttgagtatac 223740
ggttaatgta tcctggggaa aaaaatacac aacagctgtt ggattctgat ttcagttgcg 223800
aacgtcaccg gagaccgtcc acgccgttgg gaaagaacgc cgaagtgcct cccgcgaccc 223860
gcacgtcttc tacatacagc gtcctcagcg cttttgtagt gtggatcgga tccggcctca 223920
atatcatctg gtggaccggc atcgtgcttc tggcggtgga cgctctcgga cttggcgagc 223980
gttggctgag gttagcactg tctcaccggg acaaacatca cgcatcgcga accgcggcgc 224040
tccagtgtca acgcgacatg ttacttcggc aacgtcgacg ggctcggcgg ctgcacgccg 224100
tttctgaagg caaactgcag gaagagaaga aacgacagtc tgctctggtc tggaacgttg 224160
aggcgcgacc ctttccgtcc acacatcagc tgattgtgct gccccctcct gtagcgtcag 224220
ctcctcctgc ggttccctcg cagccccccg agtattcgtc tgtgtttccg cctgtataaa 224280
aataaagaga cgggaggctg atcgcggcct tcagcgtctc atttgtcttt actctcgagt 224340
gcggtcggtg tctcgtcggt gagacgaggc cgccgcccga caagttcgat ctcatgtcgc 224400
tcttggagcg cgaagagagt tggcgtcgcg tagtcgacta ctcgcacaac ctgtggtgta 224460
cgtgcggtaa ctggcagagc cacgttgaga ttcaggacga ggagccaaac tgcgagcagc 224520
cggagcccgc acactggctg gaatacgtgg cggtccagtg gcaggcccgg gttcgcgatt 224580
ctcacgatcg ctggtgtctc tgcaacgcct ggcgtgatca cgccttgcgc ggccgttggg 224640
gtacggcgta ttcctcgggt tcctcggcct cttcctccgg tttcgtcgcg gagagcaagt 224700
tcacctggtg gaaacgactg cgccacagta cccggcgctg gttgtttcgc cgccggcgag 224760
ctcgatacac tccgtctaac tgtggggaaa gtagcactag cagcggccag agtagcggtg 224820
acgagagtaa ctgcagtcta cgcacccacg gcgtgtacac acggggtgaa caacactaat 224880
cgataagtcg cgtgtaggcg actggctaca tcaaccggat atctgcgggg atttaaaaag 224940
acgacccgtt gtcatccggc ttagaccaaa ccgtcctttt atcatcttcc gtcgccatgg 225000
ctatgtacac atccgaatcc gaacgcgact ggcgtcgtgt aatccacgac tcgcacggcc 225060
tgtggtgcga ctgcggcgac tggcgagagc acctctattg tgtgtacgac agccattttc 225120
agcgacgacc cacgacccga gccgaacgga gggccgccaa ttggcggcga cagatgcggc 225180
ggttacaccg tttgtggtgt ttttgtcagg actggaagtg tcacgcgtta tacgccgagt 225240
gggacggcaa agaatccgac gacgagtcgt cggcgtcttc ctcgggcgaa gcgccagagc 225300
aacaggtccc cgcttggaag accgtgcggg ccttctcgcg ggcctaccac caccgcatta 225360
accggggtct gcggggcacg cccccaccgc gcaacttgcc gggatacgag cacgcctccg 225420
agggctggcg gttttgcagt cgacgggaac ggcgagagga cgatcttcgc acgcgggctg 225480
agccggaccg cgtggtgttc cagttagggg gagtaccccc tcgccgtcac cgggaaactt 225540
acgtgtaaga acacggcgtg acaataaaca acatagcgta aatccccgtg tgatgtgtgt 225600
gattgacgtt cgggaaacat gtccccatca tcagcgtcac aattgacgtg ggttggtcac 225660
tgacgtgcag gatgttacgc gagtcagaga atcgcataag aacggagtgg tgagcgggtt 225720
cccacaggag tctctggcgc aaaagcacca tgagcctcag gttccccgag agggtgggtt 225780
acgagaaact gggataccgc ccgcatgcca aacgcgtgcg ggtgcatgac tcgttgggat 225840
tgacgcggtt tatcatgagg caactcatga tgtacccgct ggtgttgccg ttcacttttc 225900
cgttttacgt gccgcggtcc tagcacgtca gtggtgacgc tgataattgc aacatggccc 225960
atgacgaacc cgcttgggac gaacgtcaat accacgtcaa accaccgtga cttggctgaa 226020
cgttgaaaca taaagccaaa gcgccgtcgg cacttggctt cagagcagcg cctcggggcg 226080
atgcgacggc gatgaactta gagcaactca tcaacgtcct tggtctgctc gtctggattg 226140
ccgctcgtgc tgtcagccgc gttggtccgc atggctccgg actcgtttat cgtgagcttc 226200
atgatttcta cgggtatctg cagctggacc ttctgggacc agtggtggcg gggaatcgct 226260
cagtccggac ctggagagag caggcggacc gagccagagg gaccttcgct tggcgttcag 226320
gccttaatac tagccgcatc ttacctgtcg gcagcatgta tcggggctcc gacgccttac 226380
ccgccggcct gtatcgtccc gaagaagagg tgttcctcct cttgaatcgc tgccatgggc 226440
cactgtcaac gccgaaaaat gcttgtctgg ctgaggttgg tgtcgctaat gccacttttt 226500
tgtctcgctt caatgtcggt gattttcacg gagcgtcatg ggaaaacggt accgctcccg 226560
atggagagcc cggggtatgc tgaaattcct cttaaaattt cgtaaacgac gtcgtccagt 226620
cgttgtgccg cgattcgtac ggttcatcgt ctacgtcgtt ttgttcaccg tcgctgtgca 226680
acgcgtgaaa caagagcgtg atgcgcacct tcggcggtat gaagaacgat tacggaaaaa 226740
ccgcgcacgg cgtcggcagt cttttccgtg acttggggcg atgggtccga gctgcggtat 226800
gggtcacggc ggcgtgtgtt ttattgacga agatgccgat gtgtgactaa aaacgtccca 226860
gccccagagc gatatgtttc aataaaaaaa atatgtagta tcatattatg cgtgtcctgg 226920
tttttcattt ttggatgtat gtatcgcata aagggtggcg aggtgtgagg atgaaacata 226980
tgcagatacg cagtgttgtt atccgaacga aacccgtgta atgcgtacaa cggtacttca 227040
gtatgaaagt cccgtgtgtg gggggggggg gcaaatagtt gcgtttgccg ttgggcgtac 227100
gctacgtttg tatttctggc tataatatgt gcggtcatgt gtcgatgttc ctattgggaa 227160
gggtgtgact gtagggtgta taaagtacgg tgggacgcag agggacattg atagaaacag 227220
gttgagcgct gtacgagttt cacacgctga atcggcgcca agaataaaac agtggttatt 227280
cgtaaaagta tggggggggg ggggatgttg tcgacggttg ttagatgcat tgcgtatctg 227340
tattagtagt tttgcaagcc gtggtgcgtg ttattgtgac gtagcaatta tcgtattgtg 227400
catgtgtcgt tcatcacaga gtttagtata ctaatatgaa gcgtcgcgag tattaaagca 227460
attggtgtct ctgtgctagt ctaacaacac ctgtgtaatg cgtacaacga gaaaaaagac 227520
gcgaaagcaa cgtgtatggg gggggggggg aataatattg ctaatcatgc gtcttgcagt 227580
acagatagcc gctgtatctt acgcgtattg tcgcaacagt tccacatcgg tgtaattgga 227640
tgtctggtac ttatcactgg cgtcgttata acattgtaaa acaagttttc gaaacataac 227700
gacagctgca aaagaaaacc agtttattga gcattgtaat ggtagtgtgt ggctatatta 227760
gaaaacgtga cgcgtcgcat gtcgcggcac aatctggcag cggggtcggg gtagggtacg 227820
gtgggaggca tgtacacaga tggaacaaaa gcagaagtaa cgtgagaagg agcatacagt 227880
ccagtatcca gcggttcctg agtagcacca cccatcaact gaatgccctc atgagtaaaa 227940
gtctgcgggc gacagccctt ggggaccgtt ggcatgggac gatcaatctc caaaccacag 228000
cgtaacaccg ttttcttcca acgtcgttga tagacgtcgt ttttacggtt actcccaaga 228060
acccagaaag tctcgtccaa gtcgtaccag gaatcttctc cggggagacg cgacggtttc 228120
caatcctcgt cgtctcgtct caaagcacgt cccaaactgg cttgaggagt caacggtggt 228180
tctgtgggtc gggtgtagcg cgagtgtttt cccttcatga gcgattcatc ctccttgcct 228240
ttaggctttt tggtcttttt gtgtatcatc tggccgccgg cctccataac caccgtggcc 228300
aagtccagtc ccagagcttg agcgtcggcg cggcgtcggg cgtcttgcag gtagtcttcc 228360
acatttgcac agatggccgg gtgtttggtg gctagggtga ggacctcagc ctcgccgcga 228420
cccggacgta gcaaaaaagc caactgcccg tgcggctcgc gcgcccacag cgcggcgcgc 228480
gggtgcaggt gcagcgcgtc ccagcgcggc cgctcccact gctcgcggtc cagctcgggc 228540
agcagccgcc gcgcggcctc ggcggcgggc gccgactcgc gtcccagcgc cagcgcgccc 228600
agcacgcccg cgcgcagaaa gtgcgacagc tccgccgcca gcgggtacac gtgcccgtcc 228660
agcgggcagt acccgaacac ggcgcccagc tcgtccagca gcaccaccag catggcgcgc 228720
ggcacggtcc ccgacgccgc cggacccgcc atcgctgtcg aacccaccat caccgtcggc 228780
gccgctgctg ctgccgcgtc cgccccgacc accgcgtgcg cgtccgcgtt aggcacgcaa 228840
atcgcgcccc cgccggcggc gccgtacggc tgcggaggca caggtacagc ggaccccacg 228900
gctcccgcta tcgcgcacgg cgcgtccccg ccggcggcct ccgtctccgt gccgctcgcc 228960
gctggcggcg acgtcgtccc cgccgccgtc cccgtcgccg gccccgccgc gcagcccagc 229020
caccgcgcgg gcagcaccgc gcccagcgcc agccagccgc agcacagacg ctggttcagg 229080
tgccgacgca cggccgtcag cagcgacgcg gggtgcggcg ccgacgcgaa cggctcgtac 229140
tgcgccagct cctgccacgc gcccagcagt accatcggct gcagtcgcct gcccggcgtc 229200
tgcagcgcca ccgtcgtgcc ggcccaccgc cggcgcagct cccgtccgag cgccgtcgcc 229260
tcctcggcgc gcagcaacgt ctgtcggagc gccggctgag gcagcagcgt cgcgcgcggg 229320
gtgcccacgc ccagccggtt gcagcggtac agccgcacca cctcgcccgc gccgtgccga 229380
aaccactcgt ccgcgtcgcg cgccgctagg atcagcgtgt tgtttgccag gtcgtacacg 229440
aacacgcgga acccggcgcc cagcgccagg tacagtccgt cctgcgcgca cagaccctcg 229500
ggatggccgg ccttgtcgcc caacgtcggg tcggctgcgg ggtccacctc gtgcaccacg 229560
gtagccacca gtacgatcca cgcgtcccgc ggcgacagtt gacgcaggtc cgtcgcgccc 229620
acgccgttca tctggctgcg cggcgtcacc cgcgcgtaga atccgtacgg ccgtccgagc 229680
ggcagcagcg tgcccgcgtc gcgctgcgac cacttgcgca tggcgcggcc cgtgctgttg 229740
gccaaaaacg ccgcgcgcca cacggcgccc atggcctggt attccagctc cgtcagcgcc 229800
tggcgctcca ccggaatctg agacagcaac aggcgctccg ggccgtgcca aaagttgcta 229860
ttgttgccgc tactcggagg ggcgcccggc ggcccgcggg gttctacccg gtggacgccg 229920
tggcccggcg tcgtcgtagc cgcagcactc gcaccagtgc ccgctgtgga cggcgctccc 229980
atcggcacac aagaagaagg aggagaggaa ccaacccccg aaggccctcc ggccccgcgg 230040
ccgcgaccaa ggggcggggg gcgcggcgac atgccgttgc gctgggccat gggcgccgga 230100
cacctccgac gtccactata taggaagcaa acccgcgtca gcgagcacgc ggtttagaca 230160
cgcggacgcc ttcgtcgccc gtgtgccgcg ggcgacacgc agctggcttt tataggcagc 230220
gacgtgcacg gcgcgtgctg gcgccgcctt ggcgccacgc agtctggaag gccgtggact 230280
gggaaaggca gctacccgaa ggaagacgcg cggcaggcgc gtaccactgg agcgcacagc 230340
cgcctcccgg gcgcgcaccc atctaggtgg acgcccgaca tccattccgg gccgcgtggt 230400
gggtcctcga ggggcggggg ggtgttttta gcgggggggt gaaacttgga gttgcgtgtg 230460
tggacggcga ctagttgcgt gtggtgcgga ggacggcgac ggcgaataaa agcgacgtgc 230520
ggcgcgcacg gcgaaaagaa gacgcgtgtc tgtgtctgtg tgattccccg gggaaaagag 230580
gaagttcccg ggggacggca gcatgggtcc ctggggacac acgaaaagca acgcccgggg 230640
gcgagggacg acggccctgg ggaccgcggg ggaaataacg gccgcgaggc cacacactcg 230700
ttcctgcgaa gccgcacacc ccgaggccgc gcacaccgcc gacacacccc gccaccacac 230760
cccgccggca cacccgccac acgcccgcga cacacccggc acgacacacc cggcacacgc 230820
ccgcgacaca ccctgacaca ccctgccaac acacccccga cacacccaac acacgcccgc 230880
gacacacccg gcacacaccc acccggccgc gccccgacac acccaaaaca ccgccggtgc 230940
ggggccgcgt ggtgggtcct cgaggg 230966
Claims (43)
- (a) UL128, UL130, UL131, gH 및 gL로 구성된 오량체 gH 복합체; 및
(b) 필수 단백질과 탈안정화 단백질 사이의 융합 단백질을 코딩하는 핵산
을 포함하며, 여기서 필수 단백질은 IE1/2, UL51, UL52, UL79 및 UL84로 이루어진 군으로부터 선택되는 것인 조건부 복제 결손 CMV. - 제1항에 있어서, 탈안정화 단백질이 FKBP 또는 FKBP 유도체이며, 여기서 FKBP 유도체는 F15S, V24A, H25R, F36V, E60G, M66T, R71G, D100G, D100N, E102G, K105I 및 L106P로 이루어진 군으로부터 선택된 하나 이상의 아미노산 치환을 포함하는 FKBP인 조건부 복제 결손 CMV.
- 제2항에 있어서, FKBP 유도체가 아미노산 치환 F36V 및 L106P를 포함하는 FKBP인 조건부 복제 결손 CMV.
- 제1항 내지 제3항 중 어느 한 항에 있어서, 필수 단백질이 IE1/2인 조건부 복제 결손 CMV.
- 제1항 내지 제3항 중 어느 한 항에 있어서, 필수 단백질이 UL51인 조건부 복제 결손 CMV.
- 제1항 내지 제3항 중 어느 한 항에 있어서, 2개 이상의 융합 단백질을 코딩하는 핵산을 포함하며, 여기서 각 융합 단백질 중 필수 단백질은 상이한 것인 조건부 복제 결손 CMV.
- 제6항에 있어서, 융합 단백질 중 하나가 IE1/2를 포함하는 것인 조건부 복제 결손 CMV.
- 제6항에 있어서, 융합 단백질 중 하나가 UL51을 포함하는 것인 조건부 복제 결손 CMV.
- 제6항에 있어서, 제1 융합 단백질이 IE1/2를 포함하고, 제2 융합 단백질이 UL51을 포함하는 것인 조건부 복제 결손 CMV.
- 제9항에 있어서,
(a) 제1 융합 단백질이 서열 1, 또는 서열 1과 95% 이상 동일한 아미노산이고;
(b) 제2 융합 단백질이 서열 3, 또는 서열 3과 95% 이상 동일한 아미노산인 조건부 복제 결손 CMV. - 제10항에 있어서, 제1 융합 단백질이 서열 1이고, 제2 융합 단백질이 서열 3인 조건부 복제 결손 CMV.
- 제10항에 있어서,
(a) 제1 융합 단백질이 서열 2, 또는 서열 2와 95% 이상 동일한 핵산에 의해 코딩되고;
(b) 제2 융합 단백질이 서열 4, 또는 서열 4와 95% 이상 동일한 핵산에 의해 코딩되는 것인 조건부 복제 결손 CMV. - 제12항에 있어서, 제1 융합 단백질이 서열 2에 의해 코딩되고, 제2 융합 단백질이 서열 4에 의해 코딩되는 것인 조건부 복제 결손 CMV.
- 제9항에 있어서, 게놈이 서열 14인 조건부 복제 결손 CMV.
- 제1항 내지 제14항 중 어느 한 항의 조건부 복제 결손 CMV 및 제약상 허용되는 담체를 포함하는 조성물.
- 제15항에 있어서, 아주반트를 추가로 포함하는 조성물.
- 제16항에 있어서, 아주반트가 이스코매트릭스(ISCOMATRIX)®인 조성물.
- 환자에게 면역학상 유효량의 제15항 내지 제17항 중 어느 한 항의 조성물을 투여하는 것을 포함하는, 환자에서 CMV에 대한 면역 반응을 유도하는 방법.
- 제18항에 있어서, 면역 반응이 환자에서 CMV 감염에 대한 방어 면역 반응인 방법.
- 제18항 또는 제19항에 있어서, CMV 감염이 1차 감염, 재발성 감염 또는 중복 감염인 방법.
- 제18항 내지 제20항 중 어느 한 항에 있어서, 환자가 인간인 방법.
- 제21항에 있어서, 환자가 면역력이 약화된 환자인 방법.
- 제22항에 있어서, 면역력이 약화된 환자가 HIV 또는 AIDS를 앓거나, 또는 이식 수용자인 방법.
- 제21항에 있어서, 환자가 가임 연령의 여성인 방법.
- 환자에서 CMV 감염에 대한 방어 면역 반응을 유도하기 위한 약제의 제조에 있어서 제1항 내지 제14항 중 어느 한 항의 조건부 복제 결손 CMV의 용도.
- 제1항 내지 제14항 중 어느 한 항에 있어서, 환자에서 CMV 감염 치료용 의약으로 사용하기 위한 조건부 복제 결손 CMV.
- 재조합 CMV를 쉴드(Shield)-1의 존재하에 상피 세포에서 증식시키는 것을 포함하는, 제2항 내지 제14항 중 어느 한 항의 조건부 복제 결손 CMV를 제조하는 방법.
- 제27항에 있어서, 상피 세포가 인간 망막 색소 상피 세포인 방법.
- 제28항에 있어서, 인간 망막 색소 상피 세포가 아메리칸 타입 컬쳐 콜렉션(American Type Culture Collection: ATCC)에 수탁번호 CRL-2302로서 기탁된 ARPE-19 세포인 방법.
- 제27항에 있어서, 쉴드-1이 0.5 μM 이상의 농도로 존재하는 것인 방법.
- 제30항에 있어서, 쉴드-1이 2 μM 이상의 농도로 존재하는 것인 방법.
- (a) 조건부 복제 결손 CMV를 쉴드-1이 첨가된 배지 중 상피 세포에서 증식시키는 단계;
(b) 배지로부터 조건부 복제 결손 CMV를 수집하는 단계;
(c) 조건부 복제 결손 CMV로부터 쉴드-1을 실질적으로 제거하는 단계; 및
(d) 조건부 복제 결손 CMV에 제약상 허용되는 담체를 첨가하는 단계
를 포함하는, 제15항 내지 제17항 중 어느 한 항의 조성물을 제조하는 방법. - 제32항에 있어서, 상피 세포가 인간 망막 색소 상피 세포인 방법.
- 제33항에 있어서, 인간 망막 색소 상피 세포가 아메리칸 타입 컬쳐 콜렉션 (ATCC)에 수탁번호 CRL-2302로서 기탁된 ARPE-19 세포인 방법.
- 제32항에 있어서, 쉴드-1이 단계 (a) 동안 배지 중에 0.5 μM 이상의 농도로 존재하는 것인 방법.
- 제35항에 있어서, 쉴드-1이 단계 (a) 동안 배지 중에 2 μM 이상의 농도로 존재하는 것인 방법.
- 제32항에 있어서, 제거 단계가 초원심분리 또는 정용여과에 의해 수행되는 것인 방법.
- 제32항에 있어서, 제거 단계에 의해 쉴드-1이 0.1 μM 미만으로 감소하는 것인 방법.
- (a) 15-35 mM 히스티딘; 및
(b) 100-200 mM NaCl
을 포함하는, pH 5-7의 완충제 중에 제1항 내지 제14항 중 어느 한 항의 조건부 복제 결손 CMV를 포함하는 조성물. - 제39항에 있어서, 5-15% 수크로스를 추가로 포함하는 조성물.
- 제38항 또는 제39항에 있어서, 완충제가 pH 6으로 25 mM 히스티딘과 150 mM NaCl을 포함하는 것인 조성물.
- 제41항에 있어서, 9% w/v 수크로스를 추가로 포함하는 조성물.
- 서열 14의 핵산.
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