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新的水痘病毒毒株、水痘減毒活疫苗及其製備方法

2023-06-25 19:29:36 1

專利名稱:新的水痘病毒毒株、水痘減毒活疫苗及其製備方法
技術領域:
本發明屬於生物製品領域,具體涉及一種水痘病毒新毒株的分離純化、用該毒株製備的水痘減毒活疫苗及該疫苗的製備方法。
背景技術:
水痘是一種常見、多發、有高度接觸傳播性的兒童急性傳染病,發熱的同時伴全身水皰性發疹。水痘是由於兒童感染了水痘-帶狀皰疹病毒(簡稱VZV)而引起的,該病毒主要通過空氣飛沫傳播和接觸傳染,傳染率為80~90%。
國內外業已證明,控制水痘最可靠、最根本的措施是接種疫苗,而且兒童接種一次即可獲得終身免疫。目前市場上水痘活疫苗的製備均採用的是1983年被世界衛生組織(WHO)推薦的Oka疫苗株,其是日本學者高橋於1974年從一名三歲水痘患兒的皮膚水皰中分離後,在人胚肺細胞中34℃連續培養11代後,繼續在豚鼠胚胎纖維(GPEF)細胞中培養12代,隨後在WI-38細胞中培養3代及MRC-5細胞中培養2代獲得。1995年3月17日,美國食品和藥物監督管理局(FDA)正式批准默沙東(Merck,Sharp Dohme)公司用Oka株生產的水痘-帶狀皰疹減毒活疫苗可常規用於1歲以上未曾患過水痘的兒童和成人的免疫接種,用以預防水痘的感染和流行。
除默沙東公司外,高橋博士所在的日本Biken研究所已通過商業轉讓準許比利時的史克必成(SmithKline Beecham Biologicals)、法國的巴斯德(Pasteur Merieux-Connaught)、中國上海生物製品研究所等使用該毒株進行凍幹水痘減毒活疫苗生產。中國長春生物製品研究所從韓國BORAN製藥公司引進並採用Oka株利用2BS細胞株進行水痘活疫苗的生產。

發明內容
本發明的目的在於提供另一種可用於水痘疫苗生產的新的水痘-帶狀皰疹病毒,使用該病毒製備水痘疫苗以及用該病毒製備水痘疫苗的方法。
本發明的發明人經過大量的工作,成功地從一名4歲水痘患兒的水皰液分離並純化出一新的水痘-帶狀皰疹病毒株,命名為VZV84-7株。經血清學檢測、電鏡觀察、交叉中和試驗、鑑別試驗等證實VZV84-7株確為水痘-帶狀皰疹病毒(Varicella-herpes Zostervirus)新毒株,發明人建議的分類命名為人皰疹病毒3型(拉丁文為Human Herpesvirus III)。第23代的VZV84-7株已於2006年2月10日保藏於中國微生物菌種保藏管理委員會普通微生物中心(CGMCC),保藏編號為CGMCC No.1618。
經過對其病毒基因組進行全基因序列測定分析發現,VZV84-7株水痘病毒基因組全長125123bp,G+C含量為46.1%;VZV84-7株水痘-帶狀皰疹病毒具有其獨特的基因特徵,其R2可變區重複單位的拷貝數為7個,R4可變區為9個,R5可變區為1個。本發明的水痘-帶狀皰疹病毒株的核苷酸序列如序列表中序列1所示。種系發育分析顯示,VZV84-7株水痘病毒基因組與其他水痘-帶狀皰疹病毒株的同源性為99.1%~99.6%;其不同於其他任何水痘病毒株,但與Oka株(EMBIAB097933,AB097932)、VarilRix株(GI66865971)、Varivax株(GI66866043)親緣關係較近。
本發明還提供一種減毒水痘活疫苗,其由本發明的VZV84-7毒株製備而來。其可為凍幹劑型,也可為液體劑型。單劑劑量一般為0.5ml。單劑的滴度為至少2000 PFU、優選至少3000 PFU、更優選至少4000 PFU。對於疫苗單劑滴度的上限沒有限制,越高越好,但在目前生產工藝所製備的疫苗單劑滴度最高可達100000PFU。
本發明還提供一種製備減毒水痘活疫苗的方法,包括如下步驟a)宿主細胞的培養步驟;在該步驟中,在pH6.8-7.0的含有10%(重量/體積)小牛血清的液體培養基中使宿主細胞擴增傳代;b)病毒的接種步驟;該步驟如下完成棄去步驟a)中所用的培養液,用本發明的VZV84-7的毒株感染步驟a)獲得的宿主細胞並使接種了病毒的宿主細胞在pH7.2-7.4的含有2%(重量/體積)小牛血清的液體培養基中維持生長的步驟;c)病毒的增殖步驟;即棄去步驟所用的培養液並使步驟b)得到的培養物在含有0.05-0.5%(重量/體積)人白蛋白的液體培養基中培養以使病毒進一步增殖;以及d)收穫步驟c)培養的病毒的步驟。
本發明還進一步提供一種預防水痘的方法,該方法包括對待接種的人在其上臂外側三角肌下緣附著處皮下注射單劑滴度為至少2000 PFU、優選至少3000 PFU、更優選至少4000 PFU的1-2劑本發明的疫苗。對於12歲以下的兒童一般只需接種一劑,對於12歲以上的青少年或成人一般可以接種二劑,兩劑接種間隔時間一般為一個月左右。所述接種用的疫苗可以為液體劑型,也可以是凍幹劑型。如果是液體劑型,劑量一般為2000 PFU、優選至少3000 PFU、更優選4000PFU/0.5ml/劑;如果是凍幹劑型,使用時用0.5ml注射用水復溶。


圖1VZV84-7株水痘-帶狀皰疹病毒電鏡照片圖2是顯示VZV84-7株水痘-帶狀皰疹病毒感染2BS細胞後病變形態的照片。
圖3VZV84-7株水痘-帶狀皰疹病毒種系發育分析。對VZV84-7株水痘-帶狀皰疹及其他7株水痘-帶狀皰疹病毒的進化分析結果顯示,VZV84-7株水痘-帶狀皰疹病毒不同於其他任何一株水痘-帶狀皰疹病毒株,但與Oka株(EMBIAB097933,AB097932)、VarilRix株(GI66865971)、Varivax株(GI66866043)親緣關係較近。
圖4本發明凍幹水痘減毒活疫苗生產工藝流程圖。
圖5不同代次VZV84-7株水痘病毒DNA EcoR I酶切圖譜。泳道1-6分別為λDNA-EcoR I;VZV84-7 54代DNA EcoR I酶切;VZV84-7 44代DNA EcoR I酶切VZV84-7 32代DNA EcoR I酶切;ZV84-7 18代DNA EcoR I酶切以及λDNA-HindIII酶切DNA的電泳結果。
圖6不同代次VZV84-7株水痘病毒DNA BamH I酶切圖譜。泳道1-6分別為λDNA-BamH I;VZV84-7 54代BamH I酶切;VZV84-7 44代BamH I酶切;VZV84-7 32代BamH I酶切;ZV84-718代BamH I酶切以及λDNA-HindIII酶切DNA的電泳結果。
具體實施例方式
本發明人用生理鹽水塗抹臨床水痘患者的水皰處皮膚後,用注射器抽取水皰液,立即接種於人胚肺成纖維細胞2BS株(下稱「2BS細胞」),於補加有10%(重量/體積)小牛血清的MEM(購自Gibco公司)培養液中置35℃培養,待細胞病變達75%時,去除培養液,破碎細胞,離心去除細胞碎片,獲得無細胞的病毒。經血清學檢測、電鏡觀察、交叉中和試驗、分子生物學鑑定試驗等,證實本發明人分離並純化出了一個病毒新毒株,該毒株屬於水痘-帶狀皰疹病毒(Varicella-herpes Zoster virus),發明人建議的分類命名為人皰疹病毒3型,給出的毒株命名為VZV84-7株。
隨後將該VZV84-7株在二倍體細胞(2BS細胞)中連續傳代減毒。在本發明的病毒株減毒過程中,均採用人胚肺二倍體細胞傳代,未經過動物細胞傳代。一系列生物學、分子生物學試驗證實其在體外連續傳代後毒力減弱、傳代穩定,從而獲得了可安全、穩定地用於水痘疫苗生產的疫苗病毒種子。
在上述本發明的製備疫苗的方法中,所述的液體培養基為選自MEM,DMEM,199、RPMI 1640、Eagle’s、Earle’s中的任一種培養液。在步驟a)、b)、c)中,所用的培養液可以相同,也可以不同,但優選所用的培養液除具體指明的添加物質外為相同的培養液。例如,如果在步驟a)中使用Eagle’s培養基,優選在步驟b)和c)中也使用Eagle’s培養液。
在本發明製備疫苗的方法中,所述的宿主細胞可以為選自GPEC細胞株(參見美國專利No.3,985,615)、MRC-5細胞株(ATCC CCL171,並請參見美國專利No.5,360,736)、WI-38細胞株(ATCC CCL75,並請參見美國專利No.4,000,256)、HEL 299細胞株(ATCC CCL137)、LBHEL細胞株(KCTC 0127BP,並請參見中國專利No.97190080.9)以及2BS細胞株(請參見中國專利公開CN1593657A)中的任一種細胞。
在本發明疫苗製備方法的步驟a)中,為了擴增細胞,將細胞按照1∶2-1∶10的比例、優選1∶2-1∶4的比例傳代,培養溫度為35-37℃,可以靜止培養也可以轉動培養,將細胞濃度控制在105-106/ml,培養液的pH為6.8-7.0為宜。
在本發明疫苗製備方法的步驟b)中,可在宿主細胞尚處於對數生長期時接種病毒,也可以在宿主細胞長成緻密單層後接種細胞。從感染的效率來看,在宿主細胞尚處於對數生長期時接種病毒是優選的。感染複數M.O.I.可以在0.01-1之間變化,優選的M.O.I.為0.1-0.125。接種所用的病毒優選為第31-50代的VZV84-7病毒,更優選為第32-38代的VZV84-7病毒。
在本發明疫苗製備方法中,步驟b)一般在34-35℃、培養12-24小時為宜。在該步驟中更換細胞培養液不是必需的但卻是優選的。也就是說,雖然該步驟b)可以繼續使用含10%(重量/體積)小牛血清的液體培養基,但優選的是在接種完病毒後,將細胞培養液換為含有2%(重量/體積)小牛血清的細胞維持液,原因在於這種含低濃度小牛血清的細胞培養液可以使細胞的生長速度減慢,更有利於病毒的增殖,並且方便於將培養液的pH調節為7.2-7.4。如果不更換培養基,則需要直接向培養液中加入pH調節劑。在加入該調節劑的瞬間,就會使培養體系的pH不均勻,局部(例如在調節劑的加入部位和其附近區域)的pH明顯低於或高於其它部位,從而影響了細胞或病毒的生長。如果更換培養液,則不存在這類問題,因為培養液的pH可以提前調節好。
在本發明製備疫苗的方法中,優選在步驟b)和步驟c)之間還包括用選自PBS、生理鹽水、Earle’s液、Eagle’s液的洗滌液對細胞進行衝洗的步驟。也就是說,在步驟b)結束時將含有2%(重量/體積)小牛血清的培養液棄去後,但在向培養瓶或培養孔中加入含有0.05-0.5%(重量/體積)人白蛋白的液體培養基之前,優選用PBS、生理鹽水、Earle’s液或Eagle’s液對培養細胞進行衝洗,以儘可能地洗去殘留的小牛血清。洗滌液體所用的量為步驟b)所用培養液體積的3-5倍,保證細胞培養容器的內表面的各處都被衝洗到即可。
在本發明製備疫苗的方法中,在步驟c)中,使用含有0.05-0.5%(重量/體積)人白蛋白的液體培養基優選使用含0.1%(重量/體積)人白蛋白的液體培養基。培養時間一般為24-48小時。培養基中所含的白蛋白的濃度太低,對病毒的培養不利,濃度太高則成本貴。加入人白蛋白的作用包括促進病毒增殖、加速細胞病變、使細胞病變出得整齊、有利於提高病毒滴度。
在本發明製備疫苗的方法中,在步驟d)中,在細胞的病變程度達至少75%時,吸出所用培養液,加入適當的保護劑後,採用超聲或凍融破碎細胞,離心或雙層濾囊過濾法去除細胞碎片,獲得疫苗原液。當製備液體疫苗時,所述的保護劑可以為含有25%(重量/體積)的山梨醇、5%(重量/體積)蔗糖、10%(重量/體積)明膠的Eagle’s液。當製備凍幹疫苗時,所述的保護劑為含有5%(重量/體積)蔗糖、0.2%(重量/體積)明膠、2.5%(重量/體積)水解明膠、0.1%(重量/體積)穀氨酸鈉的磷酸鹽緩衝液。
本發明的疫苗生產工藝生產的水痘疫苗各項指標均符合《WHO水痘活疫苗規程》及《凍幹水痘減毒活疫苗製造及檢定規程》的要求。
為了更加詳細地描述本發明,下面將用實施例的方式對本發明作進一步的描述。這些實施例只是用於說明目的,不對本發明的保護範圍構成任何限制。
實施例1水痘-帶狀皰疹病毒VZV84-7株的分離用生理鹽水塗抹一名4歲水痘患兒背部一綠豆大小水皰處皮膚後,用注射器抽取水皰液,立即接種於人胚肺成纖維細胞2BS株(下稱「2BS細胞」),於補加有10%(重量/體積)小牛血清、0.03%(重量/體積)穀氨醯胺、0.5%(重量/體積)慶大黴素的MEM(購自Gibco公司)培養液中置35℃培養,4天後,細胞圓縮、斷裂、變形、胞漿變圓、發亮,細胞病變沿成纖維細胞的長軸方向發展,呈帶狀分布。當病變細胞達75%,去除培養液,將病變細胞刮下,-70℃凍存,即為水痘-帶狀皰疹病毒VZV84-7株毒種,代次為第一代。
實施例2VZV84-7株的傳代將實施例1得到的第一代VZV84-7株毒種按M.O.I.為0.1的感染複數接種於2BS細胞,於補加有10%(重量/體積)小牛血清、0.03%(重量/體積)穀氨醯胺、0.5%(重量/體積)慶大黴素的MEM(購自Gibco公司)培養液中置35℃培養,逐日觀察細胞病變,待病變達到75%時,將病變細胞刮下,再接種於人二倍體細胞2BS株繼續進行傳代,每接種一次,即為一代。圖1顯示出第7代的VZV84-7株水痘-帶狀皰疹病毒電鏡照片,圖2顯示VZV84-7株水痘-帶狀皰疹病毒感染2BS細胞後病變形態的照片。在二倍體細胞2BS株上共連續傳了86代,每代病毒在接種後2~3天均可出現典型的細胞病變,病毒滴度可達4.0~5.0LgPFU/ml。因此,VZV84-7不需在二倍體細胞2BS株上進行適應,可直接使用二倍體細胞2BS株進行生產。
實施例3VZV84-7株的鑑定1.血清學鑑定將按實施例1分離得到的VZV84-7株病毒接種2BS細胞,按照實施例2描述的方式傳代。傳代至第7代後收穫感染細胞作為抗原,同時以正常2BS細胞作為對照抗原,以人帶狀皰疹恢復期血清、正常人VZV抗體陰性血清作為一抗,進行系列稀釋後,分別採用常規的酶聯免疫吸附試驗(ELISA)、間接免疫螢光試驗(IFA)及補體結合試驗(CF)測定其效價,對VZV84-7株病毒進行鑑定。結果顯示以感染細胞作為抗原測定帶狀皰疹恢復期血清效價ELISA、IFA、CF法分別為104、80、102,而以正常細胞對照作為抗原測定其效價均為陰性。陰性血清對照的實驗結果也均為陰性。證明分離的VZV84-7株病毒為水痘-帶狀皰疹病毒(見表1)。
表1 血清學鑑定試驗


2.形態學鑑定將按實施例1分離得到的VZV84-7株病毒接種2BS細胞,按照實施例2描述的方式傳代。傳代至第7代後收穫感染細胞,超聲破碎後,離心後取上清,分別經12~52%蔗糖密度梯度27000轉/分離心60分鐘、39000轉/分離心60分鐘後,取沉澱物經1%磷鎢酸(pH7.0)負染後,置電鏡(×120000倍放大)下觀察到多角形或圓形病毒顆粒,中心有一球形實體,包圍以子粒形成衣殼,直徑約75nm,衣殼之外另有1-2層膜包圍,直徑約200nm。此種病毒結構特徵與皰疹類病毒相符(見附圖1)。
3.交叉中和試驗將按實施例1分離得到的VZV84-7株病毒接種2BS細胞,按照實施例2描述的方式傳代。傳代至第24代後收穫感染細胞。將抗VZVIgG、抗人巨細胞病毒(HCMV)人血漿及抗單純皰疹病毒1型(HSV-1)兔免疫血清分別進行2倍系列稀釋,與等量的VZV84-7株病毒感染細胞混合,於37℃中和1小時後,測定血清中和效價,同時設VZV、HCMV、HSV-1病毒對照。結果顯示,VZV84-7株病毒可被抗VZV IgG有效中和,而不能被抗HCMV人血漿及抗HSV-1兔免疫血清中和。證明VZV84-7株病毒確為VZV,而非HCMV及HSV-1(見表2)。
表2 交叉中和試驗

4.純毒試驗將按實施例1分離得到的VZV84-7株病毒接種2BS細胞,按照實施例2描述的方式傳代。傳代至第24代後收穫感染細胞,稀釋成160PFU後與等量的已知兔抗VZV免疫血清於37℃中和1小時後,接種於細胞培養板,細胞生長液為補加有10%(重量/體積)小牛血清、0.03%(重量/體積)穀氨醯胺、0.5%(重量/體積)慶大黴素的MEM,繼續培養7天,觀察病變細胞孔數,結果顯示病毒對照組(未經免疫血清中和)4孔全部出現細胞病變,血清對照組、細胞對照組細胞均未出現病變;實驗組4孔病毒全部被中和,細胞未出現病變。證明VZV84-7株為VZV純毒(見表3)。
表3 VZV84-7株病毒純毒試驗

實施例4VZV84-7株在2BS細胞上的傳代穩定性研究將按實施例1分離得到的VZV84-7株病毒接種2BS細胞,按照實施例2描述的方式傳代。待病變程度達75%時,收集感染細胞,-70℃凍融2次後,加入0.5%NP-40,0.5%去氧膽酸鈉,RNase及DNase至終濃度分別為100μg/ml、200U/ml,37℃孵育30分鐘,1000轉/分離心10分鐘,取上清,40000轉/分,4℃超速離心1小時,獲得純淨的VZV病毒,採用酚-氯仿法抽提病毒DNA(Sambrook J,et al.Molecular Cloning,A Laboratory Manul,2nd.Cold Spring HarborLaboratory Press,1989)。將提取得到的VZV84-7株病毒DNA,用EcoR I和BamH I兩種限制性內切酶消化後,經1%瓊脂糖凝膠電泳進行比較,結果發現傳至18代、32代、44代、54代的病毒基因酶切圖譜未見任何變化。請參見圖5、圖6。
實施例5VZV84-7株的減毒將按實施例1分離得到的VZV84-7株病毒接種2BS細胞,按照實施例2描述的方式傳代。連續傳代至86代。結果發現隨著傳代次數的增加,VZV84-7的毒力在不斷地下降。基於各種試驗的檢測結果,將第17代的VZV84-7株作為生產水痘疫苗的原始種子,將第23代的VZV84-7株作為生產水痘疫苗的主代種子,將第31代的VZV84-7株作為生產水痘疫苗的工作種子。其中第23代的VZV84-7株已於2006年2月10日保藏於中國微生物菌種保藏管理委員會普通微生物中心(CGMCC),保藏編號為CGMCC No.1618。
實施例6VZV84-7株和Oka株的基因組的特徵測定VZV屬α-皰疹病毒,其基因組中包含6個富含GC的串聯重複序列區(R區),其中位於ORF62和63之間以及位於ORF70和71之間的兩個(R4)區相同,因此共有5個不同的串聯重複序列區域(R1~R5),不同毒株間各個可變區的重複單位的拷貝數存在差異。因為R1、R3不穩定,在進行克隆操作時其重複單位數易發生缺失,故多選用R2、R4和R5區進行不同VZV毒株的區分與鑑定,其中R2可變區拷貝數為2~13個,R4可變區為6~22個,R5可變區為1~3個。下面介紹測定本發明VZV84-7毒株和已知Oka株的R2和R5可變區、Bgl I及Pst I酶切位點區及gp I區基因的具體實驗過程1.引物的設計與合成按照下表合成用於擴增R2、R5可變區、BglI及Pst I酶切位點區及gp I區基因的引物,並在gp I編碼區上下遊引物5』端分別加上BamH I和HindIII限制性內切酶位點


*「n」表示串聯重複單位的拷貝數2.病毒株R2和R5可變區基因擴增採用R21/R22、R51/R52引物對分別對VZV84-7株和Oka株病毒基因R2、R5可變區進行PCR擴增,條件為94℃預變性5min,94℃40秒,58℃40秒,72℃40秒,進行35個循環,最後72℃延伸7min。經2%瓊脂糖凝膠電泳、溴化乙錠(EB)染色、紫外燈下觀察產物片段大小並照相。結果顯示,VZV84-7株和Oka株基因R2可變區基因PCR產物大小均為425bp,對應於7個拷貝串聯重複單位;VZV84-7株和Oka株基因R5可變區PCR產物大小分別為255bp和367bp,分別對應於1個和2個拷貝串聯重複單位。
3.病毒株基因BglI及Pst I酶切位點區突變分析首先採用Bgl(A)/Bgl(B)、Pst(A)/Pst(B)引物對分別對VZV84-7株和Oka株病毒基因BglI、Pst I酶切位點區進行PCR擴增,條件為94℃預變性5min,94℃40秒,52℃40秒,72℃40秒,進行35個循環,最後72℃延伸7min。然後將PCR產物進行酶切分析酶切反應體系20μl,含10×限制性內切酶緩衝液2μl,乙醯化BSA0.5μl,PCR產物10μl,BglI或Pst I 10U,無菌水6.5μl。37℃,4小時。經2%瓊脂糖凝膠電泳、EB染色、紫外燈下觀察產物片段大小並照相。結果顯示,VZV84-7株基因存在Pst I酶切位點,而Oka無Pst I酶切位點;但兩者均存在Bgl I酶切位點。
4.病毒株基因gp I編碼區擴增、TA克隆及序列測定按常規方法製備感受態細胞。採用gp(A)/gp(B)引物對VZV84-7株和Oka株病毒基因gp I區進行PCR擴增,條件為94℃預變性10min,94℃60秒,54℃90秒,72℃90秒,進行35個循環,最後72℃延伸7min。將PCR擴增產物純化、克隆至pGEM-T載體中;通過藍白斑對陽性克隆進行篩選,提取質粒DNA後用BamH I和HindIII雙酶切,酶切產物經0.8%瓊脂糖凝膠電泳、EB染色、紫外燈下觀察產物片段大小並照相。對含gp I編碼基因的重組質粒進行序列分析顯示,VZV84-7株與Oka株在該gp I區存在4個鹼基差異,分別在第372位、380位、438位、1056位存在4個鹼基差異,並導致第127位胺基酸改變(Gly→Val),其餘3處均為無義突變。
實施例7水痘-帶狀皰疹病毒VZV84-7株全基因序列測定將水痘-帶狀皰疹病毒VZV84-7株病毒接種到2BS細胞後,繼續培養,待病變程度達75%時,收集感染細胞,-70℃凍融2次後,加入0.5%NP-40,0.5%去氧膽酸鈉,RNase及DNase至終濃度分別為100μg/ml、200U/ml,37℃孵育30分鐘,1000轉/分離心10分鐘,取上清,40000轉/分,4℃超速離心1小時,獲得純淨的VZV病毒,採用酚-氯仿法抽提病毒DNA(Sambrook J,et al.Molecular Cloning,A Laboratory Manul,2nd.Cold Spring Harbor Laboratory Press,1989)。把VZV DNA利用超聲進行隨機打碎,回收1.5-3kb的片段進行末端補平後克隆到市售的測序質粒載體PUC18的SmaI位點然後轉化到市售的E.coli JM109。構建成功的文庫,通過質量檢測後隨機挑選菌落進行細菌培養和質粒提取,然後使用市售的M13 ForwardPrimer和M13 Reverse Primer對質粒進行大規模測序,直到測序總讀長超過基因組大小的8倍。使用Phred-Phrap-Consed軟體包對測序數據進行處理。共得到測序結果2348條;整個拼接得到的VZV全長125123bp,由2087條序列構成;序列總讀長為1269Kbp,平均覆蓋約為10X;根據Phrap軟體計算的拼接得到的VZV序列質量(consensus quality)為準確率>99.99%。所得全序列列於序列表中。從全基因測序結果還可知,R4重複單位數為9個。
製備例1VZV84-7株凍幹水痘減毒活疫苗的製備取人胚肺二倍體細胞2BS株按1∶4的比例擴增傳代,於細胞培養液(含有10%小牛血清的MEM培養液),使細胞濃度為105/毫升培養液,37℃靜置培養4天,吸出MEM培養液,按0.1M.O.I的比例接種水痘-帶狀皰疹病毒VZV84-7株,加入細胞維持液(含有2%小牛血清的MEM培養液),在34℃培養,待出現細胞病變時,棄去細胞維持液,用0.9%生理鹽水衝洗細胞表面,以去除殘餘牛血清,添加病毒維持液(含0.1%(重量/體積)人白蛋白的MEM培養液),繼續培養,在病變程度達75%時,吸出病毒維持液,加入保護劑(含有5%(重量/體積)蔗糖、0.2%(重量/體積)明膠、2.5%(重量/體積)水解明膠、0.1%(重量/體積)穀氨酸鈉的磷酸鹽緩衝液)後,破碎細胞,去除細胞碎片,獲得疫苗原液,分裝後,凍幹,製備成成品水痘疫苗。按照蝕斑法測定病毒滴度,≥4000PFU/ml(3.6LgPFU/ml)。
製備例2VZV84-7株液體水痘減毒活疫苗的製備取人胚肺二倍體細胞2BS株按1∶4的比例擴增傳代,於細胞培養液(含有10%小牛血清的Eagle’s液),使細胞濃度為105/毫升培養液,37℃靜置培養4天,吸出Eagle’s培養液,按0.1 M.O.I的比例接種水痘-帶狀皰疹病毒VZV84-7株,加入細胞維持液(含有2%(重量/體積)小牛血清的Eagle’s液),在34℃培養,待出現細胞病變時,棄去細胞維持液,用0.9%生理鹽水衝洗細胞表面,以去除殘餘牛血清,添加病毒維持液(含0.1%(重量/體積)人白蛋白的Eagle’s液),繼續培養,在病變程度達75%時,吸出病毒維持液,加入保護劑(含有25%(重量/體積)的山梨醇、5%(重量/體積)蔗糖、10%(重量/體積)明膠的Eagle’s液)後,超聲破碎細胞,去除細胞碎片,獲得疫苗原液,分裝後,製備成成品水痘疫苗。按照蝕斑法測定病毒滴度,≥4000PFU/ml(3.6LgPFU/ml)。
試驗例經國家藥品監督管理局批准,將按照製備例製備的凍幹水痘減毒活疫苗在12個月以上健康兒童中進行了I、II、III期臨床試驗,結果證實①其安全性好,未發生嚴重接種後副反應;②免疫原性高。原苗(39810PFU/0.5ml)、2000PFU/0.5ml、500PFU/0.5ml三組疫苗接種後抗體陽轉率分別為100%、98.77%、85.42%;抗體幾何平均滴度(GMT)分別為36.4、34.3、18.6,明顯優於國內外水痘疫苗生產廠家使用的Oka株。
序列表110北京生物製品研究所(National Vaccine and Serum Institute)120新的水痘病毒毒株、水痘減毒活疫苗及其製備方法130FI-060196-591601170Patentln version 3.22101211125123212DNA213Varicella zoster4001ggcccggccc tctcgcggcc ccctcgagag agaaaaaaaa aaagcgaccc cacctccccg 60cgcgtttgcg gggcgaccat cgggggggat gggatttttt gccgggaaac ccccccccgc120cagcctttaa caaaacccgc gccttttgcg tccacccctc gtttactgct cggatggcca180ccgtgcacta ctcccgccga cctgggaccc cgccggtcac cctcacgtcg tcccccggca240tggatgacgt tgcgaccccc attccctacc tacccacata cgccgaggcc gtggcagacg300cgcccccccc ttacagaagc cgcgagagtc tggtgttctc cccgcctctt tttcctcacg360tggagaatgg caccacccaa cagtcttacg attgcctaga ctgcgcttat gatggaatcc420acagacttca gctggctttt ctaagaactc gcaaatgctg tgtaccggct tttttaattc480tttttggtat tctcaccctt actgctgtcg tggtcgccat tgttgccgtt tttcccgagg540aacctcccaa ctcaactaca tgaaactact gtccggaagg ggaaggtatt tattctcgct600tgcagcttgt cgcgcgtgta tgcacaacaa aagctatata tgtcaccaaa gccaacgtcg660ccatctggag tactacaccc agtacattgc ataacctgtc catttgcatt ttcagttgcg720cggacgcctt tctccgggat cgtggccttg ggacatcaac cagtggaata agaaccgccg780gtggtcttgc acgaacgacg agtggcgacg cgttgttctg cataagctct gtatgctgat840acataaacac agagtctgta tcgctatcag attcccgaac accttccggt accccatact900ccgataccct ggacattgcg gatcccaaaa atataatatt aacaggattt gcttatactt960tgctacagct tatataaatt tatgtgcgat acatcttaag tgcatccgta cgttatttat 1020acattgcctg tcacgtgaaa agactgtgtt acccaataaa ggttctacaa aaaatgcttt 1080attgggtgtt tgtttaatag ctattatcgt aacccacccc cgtaaaatca taaaatgcat 1140gtaatttctg agacacttgc atatgggcat gttcccgcat ttattatggg ctccactctg 1200gtgcgtccca gtttaaacgc caccgccgag gaaaatcccg cgtcagaaac gcgatgttta 1260ttacgagtgc ttgcggggag aactgtagac ctgccaggcg gaggaacgtt acacattacc 1320tgtaccaaaa cctatgtaat tattggcaaa tatagcaaac ccggcgaacg tcttagcctt 1380gcccgtctaa tagggcgtgc aatgacgcct ggaggtgcaa ggacatttat tattttggcg 1440atgaaggaaa agcgatccac aacgcttggg tatgaatgtg gtacgggctt gcatttactg 1500gctccatcta tgggtacatt tctccgcaca cacggtttaa gtaacagaga tctctgttta 1560tggcggggta atatttatga tatgcatatg caacgtctta tgttttggga gaatatcgcg 1620caaaatacca ctgaaacacc ttgtataacg tcgacgttaa catgcaactt gacagaagac 1680tctggtgaag ccgcacttac cacgtcagac cgacccactc tcccaaccct aacagcccaa 1740ggaagaccaa cagtttccaa cattcgtgga atattgaaag gatccccccg tcaacagccg 1800gtctgtcacc gggttagatt tgccgaacct acggagggcg tattgatgta atcactaaat 1860aaaatacacc ttttttcgat tgtacgtatt tttatttaaa tgtgtagttc atagtccgcc 1920
gacagccgct cgggcttttc ccccacatac aacatgatcg tatgcctcgg atgcaccggt1980ccaacactcc gccgagaagg gggatttaca atgacagtga tacccaatag ccgccagatg2040tacacccagc tgtccggact ccagcatcat ctgctgagtt gcggcgctga agggtgcatc2100gcatagggtg ttataattag ccatttccgg taacagtcgt tgggaattta ggaggctgca2160aaacggctgt aggtcaacat acattgggga ttcagatggt ttatctcgac gtccaagtcc2220aatcaaaaaa gcgtgtaaat catcagcccg gccgcatgtt gctcgaagag cacataacct2280cttaacaccg tacagagggg atggcgtcgg tgcatgtgag ttggcagggc atgtccacgt2340tgtttccaac gccagtggcg gtataacttg tgtaaacgac gccaacgggt caggtttaag2400attcactcgg atgggttgac tgctttcgga agctcccgtt gtatccatta attaaacgtt2460cggtacacgt ctggtgtgtg ttttacccga atcagagacg gaattgcaaa gatattggtt2520tgaaagcaat gtaatcccgc ccatatatcc ccaacgtcgc cttaaaaact cccacaatat2580tacattttta ttagtctttt attaatatag aatcacataa acaattgata aaatcaaggg2640gtggtgtata atgattaaaa atataaattg atatgtttta caagcatgaa ataggtattt2700actattctaa caggtaaata tgcttaatga ttaaaaatac aaattagtat gttttgacaa2760gcatgaaaaa ggtatttttt attttagcag ttaaaggtac tacacttaaa atatttaccg2820tatggacggg cgtcagaaag atgcccggcc caagttgaga gggtacattc aacacgacca2880cactcgcgtt ggtgggtgat tagggcctct aaaacaccgg ccagacatga cccgggtgta2940tattcttgta acacttgaac gttacaactg atatcatcat attccacaaa tttagagcca3000cggacaacta tattagcaat gcgggcaatc ataacaaaca tataagtagt aatacacgtg3060atatcactaa aacgttgctg gcgcaacagt tcggggagag tacgagaccc caaatcgttg3120tccctgttta gaagaagaca tcttacaaaa ggccccagct ttaactttaa attctccaaa3180agtgacttcg aggttgcaac aatgggatta tttgtgtaga tgggcaagtt ttttgccgct3240aacattttaa tccacgttaa cagttcatcc gcagactcca acgcttcaat caaagattct3300ccacgtatga ctctctcacg caacgcgcgg gcaatacgtg agtccatttt atatgactca3360aaggtacgat aaagttcatg tccgtacaac atcaactccg gccaagatgt gttttgtttt3420atccccggaa aacatccacc ggaagcccat gaatcaccct cttgtattgt ggcatatcgg3480actaccagtt tttcaattgt ttcatctaaa tggcgtaccg agtcaatggt cacgctggct3540cccgcggtgg agacgacttc aatagcacgg cccgtaattc gatcgaccgg gatatcatac3600tcttttcgaa tacgctctcg gcgggcgtct ctcttggaaa atcgcaacct gtacgattcg3660tcatgtgtct gatcatttct ttctcccgtg gtcattgcag gaggcgttgt aggacgccgt3720cttcgatttg acagggatcg atcacggtgt tttcttgaac tttgggtgtt ataagatctg3780gatgatcgtc gatgtccccg ttcgatgcgt gcatatccag tctccacgtc tcttcctcca3840tgatggtttg aatcgggtaa tacaacaacc aaagttttcg ggcgattgtg gtggtagctt3900tcacgccttc cgtgccttcg tttggaatac cgtggattat atgctgtatc tgcagtacgc3960tccacataca cagttctaga cgttgtggag tcctcgcctg gagtggagcc aatagcttca4020tcatttgccc aatcggtgac ttccaatgca aagtcatccg aaggttcgtc tggtagcaaa4080ttcataaagt cttcacaaat agtagacacg tctgggtcgg ttggaattga agcagaggcc4140atggctgcaa aatatctgac aattgcgtgt ttgcagttgc ctgtatcttc cgccaatgtt4200gtagaattta taggctcacc caaccccgca atgggcgtgt ttagtcacat gattaatgtt4260tctgggagtt ttcactttcc ccaaacaagc ttacctgcac cctttgttcg taatgcataa4320aaataaccac tgctatagca aatatgacga tataaaaaca ttttatagca aggccggaca4380ttactgtagc gcaacatgtt gtgcatatac cacgtattcc ccccgtattg atatgattta4440aatgattatc cttggttggt tttggtctaa cataagatat aagctctact atagcgagcg4500tgcatacaac aacccaggcc agaatccgaa tgtatgtggg gtataataac gcgcatggtg4560tatatgcaac gccaagcgtt aaaagcacaa tacatccaga tgatatatga gcgataacct4620ccaaaagcat caataacgta acacctttat gcatatataa aaaacttata gggtcagcat4680taaatacttt actcatacca tcccgtcgca tggaaacatc acataacaac cttgccaact4740ttgtatatgg gtaaccaaga agaatgttcg aaataacccg tgttacgtaa ttcagtgaat4800atgatgtggg ggatattaac tcacaggatg atcggaatgg cccaaacata cgacgtattc4860gtcgaaattg taaatacata ccatatacaa accatgcaaa aaaaatcatt tttagctgca4920cgcaccaaaa ataagcgtga caattacgtg ttcccagaac aattcgaatt ttgtcatgca4980aaggtgtaga aatagcggtt tttaccatag tatctcctga taatagattt tcccggcagc5040tgtaatcgta tccagatagg ccatccaaaa acgttgagtg gtttacaaac gttacatata5100taagagagtt gttataagac ccccatacaa ccggtccacc attaatcacc gtggttgcat5160acacacactc atgttcaaac tttacacgag cggtatacca tagggtaaaa acagcatgtc5220cgctaagtag acacataatt ataaaatgtt ctgtcttgat tcctaaagcc tgcatgaccc5280gtggaagatg gcaattcaag cacgatgtag tatcacacgg ttggtgttaa ctcgaagtta5340aatttggata attaggtact tctagagtaa agattgtatg catgcgattg ctatcgcact5400
ttgtagcaaa acattgttgt gcaagcgaaa tacacaaacg gttgtgatga tccactcgca5460gagacacaaa tgtccgggga gccgttcttc ctccgcgatg gggatatcga agacaagtga5520acccttttgt tccgcatatg agctgaaata acacccagtc ccttttgatg gcgatacact5580ttgatgatgt taaggtatat tcgcgatcac gcccggggaa atgaacagca atatgctcca5640caatagattc taatattgtg ctgtcgacaa aggcctccag tgtaaatgcg tccagacaag5700ttaccccgcg ctcttttaga gcctttgtta aagatatttg cggggagcta aatatttgtt5760tattacgcgc aaccttacgt tcaaaaaact ctgcgtattc ccccccaagg ttatgtaaaa5820taaattgcac tggaacattc gactgcggtc ttgaatgaaa atgaaagttt gccgggtttc5880tatgtgatgt cacaaacgct aatatatcaa tacactgctc aggtacaaca taaaatggga5940gtagttgtcc aaccgccgtc cctgtggttg ttactttgga gaaaaaaggc agtcttaaac6000tatgtccgtg gctataaaca ccagtatcta taaacgaaaa gtcccgtaaa tacggaccaa6060tatattcaac aaattcccgt tccagcaaca ccgcttgctg taatatttgt gcaaacccct6120ttaaagtgga agaccccact aacgcatagg gatttgggat tggtacgcat accctgaaac6180ctattttctc tttacagtta cagggtagag tttcatgcaa gttttcattg tttgatacat6240cggcgtgtgt atggacttca gacgttgtct gtgtatcaaa aaaccataca tcctctgtat6300aattctcttc tacacacgtg tataattcgc cattttctat gtaaaaatcg atgtcagaat6360ggctggttat atccaataaa ttatcatcat ccaacacctc aacggtaggt tcaggacatg6420cagttttata aaaataacat gggtctttgt tagggtttac cacggccttt ggaaaaagta6480attgcatggc cgttaaaata ccatgacgaa atgctcgcat gccggcatgt aaaataccca6540atgggatggg ttttcttata tgaaagtcta catcaagtat gaggtttgtg attataagat6600ttgtattaaa tagctcattc ctgtttatat aaagctgatc tttgggtatg tttgatgaaa6660ttttagaaac gtttttaaca gacgtagata atagtaaagt caactgcata tctcgtagtg6720aagcggcaac aaaattacat ggattaattt gtttaaggtc ctccgcaatt aatcgagcct6780cgtgcggtaa agtgtaacgg tttgttattg atgaccacgt atcattagca ataacagcaa6840atgcttgggc gccttgaggc aaggctaccc gatatacagg cattggtcca gttacctcag6900aatggccgat gagggcttct aatggagttt tataactcag gatggataca tcatgtgtgg6960ctatcccagt ggcagcagag aaaaacagta atagttttgt aatccccggg ctcgtatcaa7020aaccagtacg accactttgg ttaggtgtat cgtttgcaaa gttggctgct cgtaacgcct7080ccgcggaaac aaccgaatcc tcaaaattag acaattcgtc aaaaccgggt ggatttgagg7140gaatagtgga ggaccatcca tatggactaa attgtttttc aatgttttcc acacgacgag7200ttagcgttgt agctaggtca catacgccta taaacttgct aggttttgcg gcatacgtaa7260gacttaaagt atatgtttta gtaattgtat atttatgtcc aatctcaggt ccaagttcag7320tgacatcaca aattacgttc ttttttatat agtcacgcat gttgagacga gaacgtacat7380gattaaaaaa attagcagta gctctttttc ccaggttgga tgattttaag aggaccggtt7440tattcacaaa atctgagtat gtaaccgctt gtaggtggtc tgcgatctgt ttccgattga7500aacattcaaa atgtgccaga taaatataat caacaaattc acggtctgga actttaaggc7560cttttctatc gttggtaata tactccgata ctgcgtgtat ttccgttgtg tctgtatgta7620ttcgctgtaa aatgtacgat agagcatttt tggctgtcaa acctcgtgta tatgttgagg7680aacaacaaaa catggaaagt ttatcaaaag acaacaagtc cgaaatattg tacccactac7740aattaggtaa tgctgggact tggtaagtta aaaacaaatc tttaattgcc tgtaagtcat7800ataagggggt ttccaacgta ttgtaacttg tgtccgtttg taacaagtaa tagcgtgtag7860ccaacactag cgttttttca gagggtccaa atcgaacaat ataccaaaac ggcgagcatc7920cataccccca gtagagtcgt cgatatgcag ccaatacttg acgttcgtaa tgggcatata7980atgatgttag ctcctgacga ccaacggatt ttttaactaa cttgcagagt gttgcctctg8040tgatgcatag gccgttgtcc gataatccct ttcggtttaa atggtgtgtt gttaccatca8100gagtttgtat aacttccgag tgaatgtcaa acgtctccga tatacatagg gtatcagata8160ttatatgcgg atttaggggt gctccatacc ataacgcctt atataaagct ttaaaatcag8220tttgggtttt aaaacaacaa aaaaatatag gccagacccg ggatcgtaca tctccagttg8280aaaatccacc aattaaataa aaaataacgt tgacgtccct actacaaaat aaatgcatta8340tttggttttc ttcatcgttt tcagttactt cacgtgggcg tttagttggg attacttgcg8400tgatctcttc cctcccattt ttgacaaaga cgtcatctaa gtcgggagtc caagtataac8460tcaccacata cagaggttct gtgcttatct gcccggtaag caacaacagc gagtgggaga8520ttgcacatcc ctttgtggca aataataacc gaatcgtcgg tttggaggat ttatccatag8580ttcaatacgt tggaaagcca gtcaatcatg cagacggtgt gtgccagctt atgtggatat8640gctcgaatac caactgaaga gccatcttat gaagaggtgc gtgtaaacac gcacccccaa8700ggagccgccc tgctccgcct ccaagaggct ttaaccgctg tgaatggatt attgcctgca8760cctctaacgt tagaagacgt agtcgcttct gcagataata cccgtcgttt ggtccgcgcc8820caggctttgg cgcgaactta cgctgcatgt tctcgtaaca ttgaatgttt aaaacagcac8880
cattttactg aagataaccc cggtcttaac gccgtggtcc gttcacacat ggaaaactca8940aaacggcttg ctgatatgtg tttagctgca attacccatt tgtatttatc ggttggcgcg9000gtggatgtta ctacggatga tattgtcgat caaaccctga gaatgaccgc tgaaagtgaa9060gtggtcatgt ctgatgttgt tcttttggag aaaactcttg gggtcgttgc taaacctcag9120gcatcgtttg atgtttccca caaccatgaa ttatctatag ctaaagggga aaatgtgggt9180ttaaaaacat cacctattaa atcggaggcg acacaattat ctgaaattaa acccccactt9240atagaagtat cggataataa cacatctaac ctaacaaaaa aaacgtatcc gacagaaact9300cttcagcccg tgttgacccc aaaacagacg caagatgtac aacgcacaac ccccgcgatc9360aagaaatccc atgttatgct tgtataaata ttgaaataaa aactaaaaac gtttctggtg9420tatgttttta ttttgtatat aaaattaaaa cattgctggc cggcgtggtt attacattta9480atgttttagt agaaaatcga catcgtttgt ttctttatca gttgaaccaa atccacgcgt9540tccccgttcg ctgggtgtgg ctattagatc taacgtttta gtaaaatacc attgtacacc9600cggtatgcca catttaccgc ggatagcata aggaaatgca atattactta aaacgttgtg9660ttttaagtgt atttgggtgt tgtgatctat taacaggacc tgtgcaagac gatctcccgt9720ttttatacgt atgtcatcac ccgtgagatt atatacgtag aatttacagt gttctcctgc9780aggccatgcc gttggacaca cgataatgcc tgatcggctt ttcgatgatc ttccaaaaat9840ataagcgttt atactcggat gttgtaagtc ccagtctctt ataatcggta agacaatttt9900tataaattca ttccttttta aatataggtt atatggtaca caaatatcat atcccgcgtc9960ttcttggcgt tttggattga tgatatgttt gtaggttaag ggaacatcga tatggtattc 10020tgcagaatcc ctatgtaaag gttgcccctg ctgtaccgtg gaaatatcag caaattcaga 10080tataacgggt ttttcataat ttgacggcga gtttgataag ggttgaactt gtatcgattt 10140aaaaattgga tccagatgtt taagaacgtt ttttgggaga aggcgacttt gtcttaattt 10200taccgggaac aagtagattg ttaaatgtcc gggtaaaata acggttactc ctggccggta 10260atacaaaagg gctgaaatta ctcctctgta acccgcatca ataactccgt tggcgacaaa 10320aaaattgtct tcatcagcaa gggcagtatc tttgcattga attaacaaca gtgcgtattc 10380attgggaggc gccgacttaa ccaacagctc caactgctgc atataaaaac cgccccgtgt 10440tacagatttt tcagatggca gttcgagttt cttgtggttc cggagtaaca acggttgatg 10500tcgacttact ttatcgtcta acacgcattg cagcgtatct gcacattcag gttgaacttc 10560tattaaaatt gtatctttta aacaccgatt cggaatagtt tggctacaaa acatatcacc 10620tgtatttact gccgtttcca agatgggatc aattaccgct tcgttcatat taataacgat 10680gcaaatttta tttttttgtg aagacagcag tggggagcca aactttgcag aacggaattt 10740ttggcatgcc agctgttcgg ctcgtggagt ttatatcgac ggatcaatga tcaccaccct 10800tttcttctac gcatcccttt tgggggtgtg tgtagccctt atttcgttag cttatcatgc 10860gtgtttccgg ttatttactc gttctgtatt acgcagcacg tggtaaaccc gtttgcctat 10920aaaaggggca ggcgtgtata agagggcccc tgtttaatac gcggtctgcc gtgtttggat 10980atttcacgac cctatcgttt atttacgtaa tggcatcttc cgacggtgac agactttgtc 11040gctctaatgc agtgcgtcgt aaaacaacgc ctagttattc cggacaatat cgaaccgcgc 11100ggcgaagtgt ggtcgtagga ccccccgatg attcagacga ctcgttgggt tacattacca 11160cagttggggc cgattctcct tctccagtgt acgcggatct ttattttgaa cataaaaata 11220cgacccctcg cgtacatcaa ccaaacgact ccagcggatc ggaagatgac tttgaagaca 11280tcgatgaagt agtggccgcc tttcgggagg cccgtttgag acatgaactg gttgaagatg 11340ctgtatatga aaacccgcta agtgtagaaa aaccatctag atcttttact aaaaatgcgg 11400cggttaaacc taaattagag gattcaccga agcgagctcc cccgggagca ggcgcaattg 11460ccagcgggag accaatttcc ttcagcactg caccaaaaac cgcaacaagc tcgtggtgcg 11520gtcctacgcc atcatataac aaacgcgtct tttgtgaagc ggtccggcgc gtagccgcca 11580tgcaggcaca aaaggctgcc gaagcggctt ggaatagtaa tcccccaagg aataacgccg 11640aattagaccg tttgttaacc ggagccgtta ttcgtattac ggtgcatgag ggtttaaatt 11700taatacaagc cgctaatgaa gcagacctag gtgaaggagc atcggtatcc aaacgtggac 11760ataatcgaaa aactggagat ttacaggggg gcatgggtaa tgaacctatg tacgcacaag 11820ttcgtaagcc aaaaagtcga acggatacac aaacgactgg gcgtataact aatcgaagta 11880gggcccgttc ggcatcaaga actgatgcgc gaaaataggg atataattac gcagtaacgg 11940tttacccggt attatgtata ataaataaac gtataaaaga cagtcgtggt ttgtgtttat 12000tataaatgtg tattatatgt cacatattat aaactgttta aatagtacca cgtggtatta 12060tgaacagttt ataatcagtt gctaccaaac aaaccccatt agacggcggg ttttgataaa 12120gggaatcgct tatttaaact aaagatttta ctctataagt atggagtgta atttaggaac 12180cgaacatcat agtacagata cgtggaatcg tagtaaaacg gaacaagcgg ttgtggacgc 12240atttgatgaa tcgttgtttg gtgatgtagc atcggatatt ggatccgaaa cgtcgttata 12300ttcacatgca gttaaaactg ctccgtctcc gccttgggta gctagcccta aaattttata 12360
tcaacagtta atacgggatc ttgatttttc agaagggccg cgtttactat catgtcttga12420aacctggaac gaggatttat tctcatgttt tcctattaat gaggacctat attccgatat12480gatggtttta tccccggatc cagatgacgt tatctcaacc gtttcaacca aagaccatgt12540tgaaatgttt aatttaacaa cccggggttc cgttcgattg cctagtccac caaagcaacc12600gacggggctt ccagcttacg ttcaggaggt ccaggattcg tttaccgtag aactacgcgc12660ccgggaagaa gcatacacaa aactactagt tacttattgt aaatcgatta tacgttatct12720ccaaggaacg gcgaaaagga cgacaatagg tcttaatata caaaaccctg accagaaagc12780ttacacgcaa ctcaggcaaa gtattctact tagatattat cgtgaggtgg caagtttggc12840gcgtcttctg tacctacatt tatatttaac cgtaacgcgt gaattttcct ggcgtttgta12900cgccagtcaa tctgcacacc cggacgtgtt tgcggcttta aaattcacct ggaccgaacg12960tcgacagttc acgtgtgcgt ttcatcctgt attatgcaac cacggcattg tgttattaga13020agggaaacca ctaacagcgt ctgccttgag ggaaataaat taccgccgcc gagaactggg13080actgcctcta gttagatgtg gtcttgttga agaaaacaaa tctccgttgg ttcaacaacc13140ctcattttcg gttcatttac cacggtcggt ggggtttctt acccaccaca ttaagcgtaa13200gttagacgca tatgcggtca aacatcctca agaaccgaga catgtacgag cggatcatcc13260ttacgcaaaa gttgttgaaa atagaaacta cggtagtagc atcgaagcta tgattttagc13320acctccgtcc ccatccgaga tcctgccggg ggacccacca cgcccaccca cgtgtgggtt13380tttaacgcgt taaacgtcat tggggtaaag ggtgtaaata aattacgaaa acgtgcatgc13440gttttttatt tttacaatgc gccgtatatg gtatgtctgt catgtgctct aaagtcccat13500atataaaaga agccccaacg agtgtatgcg tattgcgtac cgcgaccctg ggatgtttta13560caggcgcgtt tgtttgtctc ggttaaaagt atgcagtcgg gtcattataa ccggaggcaa13620tcccgccgac agcggatatc gtctaatacc acagactccc cccgtcacac acacggaaca13680cgttatcggt caaccaattg gtatacacac ccaccccaga tattgtccaa ttcagaaaca13740ttagttgcgg ttcaagaact actgaactcc gagatggatc aggacagcag ttctgacgca13800tcggatgatt ttccgggata cgccttacat cattctacat ataatggatc cgaacaaaat13860acatcaactt ccagacatga aaatcgcata tttaaattaa cggagaggga agctaatgag13920gaaatcaaca tcaatacgga cgcgatcgac gacgagggag aggcggagga gggagaggcg13980gaggaggacg cgatcgacga cgagggagag gcggaggagg gagaggcgga ggaggacgcg14040attgacgacg agggagaggc ggaggaggga gaggcggagg aggacgcggc ggaggaggac14100gcggcggagg aggacgcgat cgacgacgag ggagaggcgg aggaggacgc gatcgacgac14160gagggagagg cggaggagga ttatttttct gtaagtcaag tttgcagtcg agacgcggat14220gaggtttatt ttacgttaga cccggaaata agttacagta ccgatcttcg cattgcaaag14280gttatggagc ctgcggtatc aaaggaactt aatgtatcaa aacgttgcgt tgaacctgtt14340accctaacag gctctatgtt agcgcataat gggtttgatg agtcctggtt tgctatgcgc14400gaatgtaccc gtcgcgaata tattacggtc caaggattat acgacccaat tcatttacgg14460tatcagtttg atacttcccg gatgacaccc ccacagattt tgagaactat accagccctt14520cctaacatga cacttggtga acttttattg atttttccta ttgaatttat ggcccagcca14580atttctatag aacgtatttt agttgaagat gtatttttag ataggcgggc ttccagtaaa14640acacataaat acggcccgcg ttggaattcc gtctacgcac ttccatataa tgcgggtaaa14700atgtatgtac aacacattcc tgggttttat gacgtgtcct tacgtgctgt gggccaagga14760acggccattt ggcatcacat gatattatcc acagcagcat gcgctatttc taatcgcatt14820tcacatggag atggattagg atttttgtta gacgcggcaa ttcgtattag cgcaaactgt14880atttttttgg gacgtaacga taattttggc gtgggggatc catgttggtt agaagaccat14940cttgccggat taccacgaga agccgtaccc gacgtactcc aagtgacaca gttggttttg15000ccaaatcggg gtccaacggt tgccattatg cgtggttttt ttggggcgtt ggcatattgg15060cccgaactaa gaattgctat aagtgaacca tctacatctt tggtgcgata tgctaccggt15120cacatggaac ttgccgaatg gtttttattt tcacgtacac atagtttaaa gccacaattt15180accccaacgg aacgggaaat gttagcgtca ttttttacgt tgtatgttac tcttggtgga15240ggaatgttga actggatctg tagagcaact gcaatgtatt tagctgctcc ttaccattcc15300cgttcggctt acatcgcggt ctgtgaatct ctgccctatt actatatccc ggttaatagt15360gacctgttat gtgatttaga ggtattactg ttaggcgagg tcgacctccc aactgtttgt15420gaatcctacg caactattgc acacgaatta accggatatg aggctgttcg cacagcagcc15480acaaatttta tgatagagtt tgccgattgt tataaggaaa gtgagaccga tttaatggta15540agcgcgtacc tgggggccgt tttattgtta caacgggtgt tgggtcatgc aaatcttctt15600ttgttgcttc tctccggtgc tgcgttgtac ggaggatgtt caatttacat cccccgaggt15660attttagatg catataatac tttaatgttg gcagcaagtc ctctttacgc tcaccaaact15720ttaacatcct tttggaaaga ccgcgatgat gcaatgcaaa ctttggggat tcgaccgaca15780acggacgttt tacccaaaga gcaagacagg atagttcagg catcacctat agagatgaac15840
ttccgttttg tgggattgga gaccatctat ccccgagaac agcccattcc ctccgtggac15900ctagccgaaa atcttatgca atacaggaat gaaattctgg gtttggattg gaaaagcgta15960gccatgcatt tactacgaaa atattaaggg ttgtgatttt tttcattagg atgaaaagaa16020cgtttcctag ccacacccac aaaggagttt gtaaaataaa atctctgttt agaccttaaa16080atttgttgtg tgtgttgtgt ggggggtccg tgaggatcga cctttacaag atataatttg16140tccatatcgc aatgttttct cggtttgcgc gttccttttc cagcgatgat agaacgcgta16200aatcttatga tggtagttac caaagtttta atgccggcga acgtgatttg cccacaccta16260cccgggactg gtgttctatt tcccaacgca taaccagcga gcgcgtgagg gatggatgtc16320ttattccaac gcccggcgag gctttggaga cggcggtaaa ggctttatct gaaaagaccg16380acagcctaac atcgccggtt ttacaaagta ccgaaagaca cagtgttctg cttggattac16440accataataa tgttcctgaa tcgttggtgg tctcgtgtat gtctaacgat gttcatgacg16500ggtttatgca gcgttatatg gaaacaattc aaagatgttt ggatgacctg aaactttctg16560gggatggact ttggtgggtt tatgaaaata catattggca gtatctcaaa tacaccacag16620gagccgaggt accggtgact tcagagaagg taaataaaaa gtctaaatcc acggttttgt16680tgttttcatc cgtagttgcc aataaaccaa tatccagaca tccttttaaa tctaaagtta16740taaattcgga ttaccgggga atatgtcagg agctacgtga ggcgttagga gctgtgcaaa16800agtatatgta ttttatgcgt ccagatgatc ctacaaaccc cagcccggat acaagaatac16860gtgtacaaga aattgcggct tacacggcta ctggctacgg gtggatgtta tggttcttgg16920acgttgtgga cgccagggta tgtcgccatc tcaaacttca atttcgacgg attcgagggc16980cgcgcgcgtc tgttattcca gatgatttgc ttagacgaca tttaaaaacg ggtcctgcgg17040tctcagcggg cacaggagtt gcgtttattt tagcagcaac aactgccagc gctcttactg17100cgcttttgcg tattagtgta ttatggcgaa aggaagagtg gcgggatggt ttaaatggaa17160ccgcagctgc aattgttgcg gcggttgaac ttattacgct tttgcaccac cattttcaat17220acttaattaa tatgatgctt attggatatg catgttgggg ggatggggga ttaaacgatc17280cttatatatt aaaggcgcta cgtgcccagg gacggttttt atattttgcg ggtcagttgg17340ttagaacaat gtcaacacac agttgggttg tgttagagac cagcacccat atgtggtttt17400cccgggccgt ggcgcagagt attttagcac atgggggtaa acccacaaag tattatgctc17460aggttcttgc cgccagtaaa cggtatactc cgttacattt aagacgtata tccgaaccat17520cgagtgtgtc tgatcagccg tatattcgtt ttaatcgact gggatctcca atagggacag17580gtatagggaa tttggaatgt gtctgtttaa cgggaaatta tttatctgac gacgtaaatg17640caagttcgca tgtaattaat acagaagcac cgttaaacag tatagcaccc gatacaaata17700gacagcggac ttctcgcgtt ttagttcgtc cagacacggg tttggatgta actgtccgaa17760aaaaccactg tttggacata ggccatacgg acggtagtcc agttgaccca acgtatcctg17820atcattacac ccggataaag gcggaatatg aaggtccggt tcgggatgaa tcaaacacaa17880tgtttgacca aagatcggat ttacgtcaca tagaaaccca agcatcttta aatgatcacg17940tatatgaaaa tataccaccc aaggaagtgg gttttaactc atcttcagac ctggatgtgg18000atagccttaa cgggtacacc tccggagaca tgcatacaga cgatgactta tcaccagatt18060ttatacccaa cgacgttccc gttagatgta aaaccacggt tacgtttagg aaaaatacgc18120ctaagagtca tcattaagta cagcggttaa tagatagtta tggactaggc actttggcgg18180tcatttccac aaccaggtta aaattggggg atttgggaga aaatagtcta ttgcgtattt18240tctgttcaat aattggactg cgttatttaa aggtctgatt ggttgattgg gttataaaag18300gaattactcc tttaaatttt acttaatgta cccacaatat caagtggtcg tttgtattta18360acgattatta ccggtaccat gggagacttg tcatgttgga caaaagtgcc gggttttacg18420ttaaccggcg aacttcagta cttaaaacaa gtggatgata ttttaaggta tggagttcgg18480aaacgcgatc gaacaggaat cggaacgtta tctttatttg gaatgcaagc tcgatacaat18540ttgcgaaatg aatttcctct tttaactaca aagcgtgttt tttggagggc cgtcgtggaa18600gagttgttat ggtttatccg cgggtcaacc gattccaaag aactcgccgc taaagatata18660cacatatggg atatatacgg atcgagcaaa tttctaaata ggaatggctt ccataaaaga18720cacacggggg accttggccc catttacggc ttccagtgga gacattttgg agcggaatat18780aaagactgtc aatcaaacta tttacagcaa ggaatcgatc agctgcaaac tgttatagat18840acaattaaaa caaacccaga aagccgacga atgattatat cgtcttggaa tccaaaggat18900atccccttaa tggtactacc tccatgtcac acgttatgtc agttttacgt tgcaaacggt18960gaattatcct gccaagtata ccagagatcg ggggatatgg gccttggggt accgttcaac19020attgctggat atgcacttct tacctacata gtagcgcatg ttacaggact taaaaccgga19080gatttaattc atacaatggg ggatgcacat atttacttga atcatataga tgctttaaaa19140gtgcagctag ctcgatcccc aaaacctttt ccttgcctta aaattattcg aaatgtaaca19200gatataaacg actttaaatg ggacgatttt cagcttgatg gatataatcc acaccccccc19260ctaaaaatgg aaatggctct ttaatggatt tttaaatgtt gtcaagacag tagatgtgtt19320
gcgaatgtaa taaaatgata tacacagacg cgtttggttg gtttctgttt atgaacagca19380acggatgcat agggttgcga taactgcgat aagacccaat gtcccaagga tagatatcac19440accaattata actgctacaa cggaaaatgt agtggcgtag gtagatgcat cgtaggtata19500aacggccgaa aacggaggga attttttagg gtaaccatct agatgacacg aataggtgat19560aggtccgtcg agttccgatg ttggacaaga actttgcatg tttacaaacc gtttgttttg19620atcacacacc ccagtaatct cactgttttc gtggttgatg ggagaatcgt taacccacca19680tacgaaatgt acaacgccac gtggcacaca ttttgccgta catactatgt gtccatcaat19740aatacctata gacacgttgg gaaatggata gacgtcaggg gtaacgacag cagaatattt19800catattagag acgccatccc gaatccataa aacattacat tggatggctg ggggtgggta19860atccatttgt ttttgctgtg gaattcgtac cgccgaaaca taactaaata atccattggc19920atattcttgt attgcatcgg ttataaaatt ttttccgatg ttaccaaacc ttgaagtcca19980ccgaacacgt accgagtgcg gtggataata ctttgatacg ttacagtagg ctgcgtatgt20040ctgtccggtt aagactggat cgccgacaac ggtaatattt ggacgataat acgttgtaac20100tgtaatactg tgttccgata tgacgttctt agtttttgta ttaacgactc gccaaatata20160cgttccctcc gtggtagcat ccatagataa aattgttaca gaaaaatcag acgttgtttt20220aacatctggt attacataat tttccttagc gtgtgtaaat atctcagggt tgtttattaa20280gtttaaatcg gcactgttgc tatataacat aaccggtaaa tctggcatgc gtattaacgc20340attgcccagt tgacggtgcg gatctataag gtgacgcgta aaccaaactt caatatgaag20400atcggggcgt ataagcgact tccaccttgt tatatttgaa ccttccggat ctaaagaata20460ttgttcatat gttttttgtt gctgcttaaa ggccgcctgt tgtccggtcg ttagacgcat20520gtaacaaggc atgataaatg tgtgaaaata gggtatggat tgtattccgc cgtgaacgca20580ttgtatattt tcaaatagaa aaggtggttg tgaatgttgg gcgttggctg cgggatcggg20640ctttcgggta gcggccgagg tgggcgcgac ggcgggatcg ggatttcggg aagcggccga20700ggtgggcgcg acggcgggat cgggatttcg ggaagcggcc gaggtgggcg cgacggcggg20760atcgggcttt cgggtagcgg ccgaggtggg cgcgacggcg ggatcgggct ttcgggaagc20820ggccgaggtg ggcgcgacgg cgggatcggg atttcgggaa gcggccgagg tgggcgcgac20880ggcgggatcg ggctttcggg tagcggccga ggtgggcgcg acggcgggat cgggctttcg20940ggaagcggcc gaggtatata attcagttat acttacgggt gtgggttgag attcagtcga21000taattgtata cacgcgatcg ttaaaattaa atttatttgt atccgcttca tcctggtttt21060tattgacaca tccacgctcc ccttaaataa aagattaaaa cacccaccgc ggaatttaaa21120tgatggaaac gtttttttcg acattgggaa taataaaaac ggcttttgca actttaaaaa21180ctttatttat ctcgattacg atacatatgt accacataga tagcatagat ttattataat21240ataaacacac acgtgatata ctttagtgat atgagatgcc ataaaacagt caataggttt21300aacgcttaat ctcatcatct gaatacacgt caaacccgcc gcaactgttg atgttagaat21360tataatagct ccccatgaaa tgccggcaaa tgttacagct atacccgtca ccgaggtcgt21420tgtatataat acaattaccc ataggttttt tttttcttga tataaaacgg caaaaccctg21480taacccaaat gctataatat gacctcctat tgaaactgct aacgttactt gtgtaagttt21540gataaaatga tttaatttaa ttatatgtga gattgcccac attaatgggg taactatata21600taacaccggg ggtataacag acattatacg aattccttta aacacgcgtt taagggtccg21660ggaactttct ctatggtcac atactctccc gcggtcattt tgtgtatata caacggcaaa21720acctaaatct gtataagtgt ttaattgctt atggcgattt ttacgatata tacacgtatc21780ttgcaaatcg gtggcggcat cgacaattga aactagtgtg acaatagata tacacaatcc21840aataagaacc tcatatttac tgacatacat atataaaata acggttagta aacctcccaa21900cccagttccc aacatcataa cataaaaata aatatgcggt ccattgaatg tcgtaacaaa21960gttgtagtaa tggatatgca cagcagccac tgttccggta atcgcggata tggaaattcc22020cagtaattct acaaatggaa gatcccggga tattgggcaa ccaaccgccc ataacacagc22080aaaacccaac acgaccaccg tctgcaaaca tcgtcccaat tttgctaatg tgcgtagaaa22140tttcacggat gttggccata accccgaaac gacgatcaac cccataatag ttgcattgac22200ggcagcttcg cagacgtgat attgtaaaat taacccggac gtgataacac ttgcttgtag22260tcccacgaga aacaaccgcg atgctgaggt tattgcacac gaattacatt cttgagggtt22320tccgacacat ccttggattg attgagcgcg gattaattct ctgtctaaca cacccaggtt22380ttcatcatgg acagctcttt caccattcac ggccatgtct taagtttaat aattcaaaac22440agataaaaat gtgttcatct atggtacaca caagtttgta tgtaaaatat aagcaaaagt22500tgcacttatt taactgtaca tattacgtca gattcacgtg ataattcaga ataatccagg22560gttcctgcag ggtccactgg aggagccaca caatattcgc gaattccgat tccctcctgc22620catgtggttt cggggagttt cccccccatt ttatttccgg tatttttttc gtttcttttt22680gttaataaat tgcgtctttt ttttaatggt ggttcatcct tcacagattc cgtgttcgca22740aataattgca tcgaggttaa tttttcttta aggtctttgg gacttaagaa cgttgcataa22800
aaaaaagaat gcacgggtgc ggaacgttgg atatacaatc caaccatggg ggagttagtt22860aaggcgagat aaaaattaat ataacacgtc tcatcccgtg ttaacttaag attttgtacg22920gcagaacgga atccactgtg tgtttccaat aatactccaa attcacgcat actcccgctg22980ccataaacaa cattattaag gatccttttt gaatttgtga ttgagcgtat taaattatat23040ggtgtaggct tgcttccgtt tatatccaag gaaacattaa atgagataaa accacccccg23100gcggtctgga tgtacatatc cgtggctgtt agaatgaagc atgttgtaaa cccaaaagtt23160ttaagtagtc gctgtaaacg ggtgaattga tcgcgtttta agcaaatgct tatatctgga23220gttagatttg ggaacatcat tgtataacaa gcgagttcac gttttacaac ttgtttgtaa23280cattgtactt gatcatctgg accacaatca cccgggcgtt gccataccat cgtttggata23340atactccgct cggggggttg tccggtaaat ttaaaatata accgtgttgg ggtcgacgga23400tcttttgtat ggcgaaacgc gtcaataagc gaggaccgtc cctccgttgc cgcgagtaca23460accattctcg gcccagtcca attatactgg tcaaacatat ttgccggtat aggaatatac23520agttgttctg tttccaaact acagtgaata attaatcctt cgtcgctgaa tattaaaata23580gaatccctta gtctattaac cagaggtgat atagacgaaa ttaaaccagt aagcgttttt23640tccgttaaaa cagctctggc gatttctggg gcgtcaaaac ccgcatgcaa ttccatgtcc23700aaagcatcgt ctgtacgcga cctcaaatcc ataatttact acttaaaatg tttactatag23760aaaaagtaat catatgtaaa cacacgagtt tcgttaatat gtttgtttaa cccgatccgg23820tgacttaagt acataaacag gcatgatatt tgaatagtac ggcccatggg agggaacatt23880tccacgtgtt ccaatacagg gggtgttcct taatagggac tgtgcaataa aatacgtaag23940aagttaccag atttgatgta atgtttgtca taaaaaatat gtacatcatt atatacgtct24000gtaattaaca caagatcaca tcgaagaatt actgaagccg ctgtgaaacc tttcacaaga24060cgatataaac ttggttaagt gtattgatgg ggctctttgg actgacacgc tttatccatg24120aacataaact ggttaaaccc agcatcattt caacgccacc cggagtttta acccccgtgg24180cggtagacgt atggaacgtc atgtacacat tgttggaacg tttataccct gtgggtaaac24240gcgagaattt acacggacca tctgtaacga tacattgtct tggagtctta ttgcggctat24300taacacaacg gtcatactat ccgatatttg tattggaacg ttgtacagac ggcccattat24360cacgtggagc caaggcaatt atgtcacggg ccatgaacca cgatgaaagg ggaacctcgg24420acttaacccg tgttctacta tcatccaaca catcatgttc tatcaagtat aacaaaacat24480cggaaacata tgacagtgtg tttcgaaact cttccgcgag ttgtattcct agcgaagaaa24540acaaatccca ggatatgttt ttggacggtt gtccacgaca aactgacaag atgatctgcc24600tgcgcgacca aaacgtatgc agtcttacct ctacaatgcc atcccgagga catcctaacc24660atcgattata tcacaaattg tgtgcaagtc ttattagatg gatggggtat gcatacgtcg24720aggcggttga cattgaggcg gacgaggcat gtgcaaactt atttcatacg cgtacagtgg24780ctttggttta tacgacagat actgatttac tcttcatggg ctgtgatatt ttgttagatg24840caattcctat gtttgctcca gtagtacgat gtcgcgattt gcttcaatat ttaggaatta24900cataccctga atttttggtt gcctttgttc gctgtcagac cgatttgcat acaagtgaca24960acctaaaatc tgttcagcaa gttattcagg ataccggcct gaaaattcca catcaaatgg25020acacttcaac gcgctccccc acttacgact cgtggagaca tggcgaggtt ttcaaaagtc25080ttaccgtagc cacgtcgggt aaaacagaaa acggagtgtc cgtttccaaa tatgcatcta25140accgatcgga ggtgacagta gacgccagtt gggctttaaa ccttctgcca ccctcatcct25200ccccattgga taatttggaa cgcgcatttg ttgaacatat aatcgccgtg gtaactccat25260tgacccgcgg tcgcctaaag ttaatgaaac gtgtaaatat tatgcaaaat acggcagacc25320catatatggt tattaacacc ttatatcata acttaaaggg ggaaaaaatg gctcgccaat25380acgcacgtat ttttaaacag tttattccta ctccactccc actaaacact gtattaacaa25440aatattggaa ttaaaacaca cataagagcg acttaatggt tcattgtttt attttgctcg25500tatatacatg ttataaatcg tttatcactg tgcccgcata agatgtactg tgtctctcaa25560aaaaatttgt gtttttatct gcaatcataa atgcaagtgg aaagtccgaa tcgggaggtg25620gggtgttaaa tagttttggt acattaatcg ctgataaaag cctgtccgcg ctgaatttca25680cgtattgtgt aattgcatcg acgttcacca aacgggtttt gggtgcatgg gattttaaaa25740acgcacactc gatttcaacg gcttccgaaa acagttgatg tattctggtg atagcgggtt25800tttcgggtac atagttattg tatatacaac acgatgcgct ggtatgtatg gcttcatctc25860ggcttataag gtcgttaaat tgacaagtta caacaaatag tccgttattg cgtaaatatg25920caatagccgc gaacgatgat acaaaaaaaa tgccctctat aagaatcatt agtatatatt25980tttctgcaac ggatgggttg tcccgtacct tttcttccaa ccattgtact ttttgttgga26040tcgacggatt attaatagtg acatttacgt attgtacccg caacgattca tcccctctga26100acaacattag ttgaatttga ctatagacac gcgcgtggac aacctcgatg cactcttgtt26160caatgtagta atggtgaata tccttttggg aaaagagttg ggttagagag cccaaattaa26220catttaccag atcatctgcc gccgataaaa atgtaaaaat aaatctgtag aatattagtt26280
catcttccgt taaacagtcc aagtattgat aatcatcttc aatgataaaa tcgctttcta26340accaacgatt cgaaatgctc agggcacgta aattgtttat atctggacac tccggcctgt26400aaaaaaaatg actgcaatct ttctgatcca ttttggaata gtttcccgtg taaatttata26460aagcacaact ggtacaggtt aattcgcctc ccgcaaacag tccgctgttc gtagctttac26520gaattttaca gtagtacata cccgttttaa ggccggcttt ataggcacgt ataagcaaat26580tcattatttt ggaggcggga attgtcccgt ctgggcgttc ctcaataaat aaagtcattg26640attgactttg gtcaataaat ggcgcccttt ctgcacacat atcaacgaga tcctcttgct26700catattcaaa cgctgtttta tattttaaga gtgggtgact attagataaa cagccaaacg26760aacgtattac tgaccattgg tttttctcaa gtatgtttat aacttccagt cgtttttctt26820cacatgaata catatctctt agttcgtcca taaggtctaa gttgggtcta agtaactcac26880ccgaggtggt gaccttacta aacatattat tataaattgg agagaaaccc tcactgcact26940ccgttacctg tgcagatgaa actgtgggca ttaacgctaa gaactgcgag ttgtataacc27000cataagcgca aatatcatct cgcagggtac accatggtaa atctaaataa cttatcgtag27060aaaacccatc ttggtgtaac catcccttag catatttact ttcggtaaaa cccttaaacg27120gggctaagcc gccaatctta cacatttcca tgcttgtttt cattgtctca tacaacatta27180actccgctat ttgtacattt aaccgtctag ctggttggga agttaaatca aatcctaagc27240ggagacaagt tgtatgtaac ccttgtatgc caatgccaag tgatcggttg ttttttacac27300ctttacatga ttttttacat ggaaagttcc cagccgccag gaccccgttt aaaaaaataa27360cagtcgttct tgctgtcaat tgaaggtcgt ttaaattaaa tgacactggg cctttggata27420agcacgttgt aagatttatg ctggcaagat tacatacgcc atgttgatga gcgtctgcct27480tttgaacaat ttccgtacac aaatttgacc ccgtgatagc atttccttgg gtattcatat27540gataattacg attacaggca tctttgaaca ttaaaaaggg gcttcctgtt acagcagcac27600tgcgtatgat tgtgaatgcg atatcttgaa tgggaacaga agaaacgcct aatccttctc27660tctctaaacg taaataggtt gaagtgaatg cctccccgtg taatgttcga aggatatcgg27720ctctgttatc aaaaagagtc cactgaacat tactagcccc ttttagatag cttaggtatc27780tttcaaaaaa taaatctggg gtccataaac aacaaaatat gttatcacat cgaaatattt27840catcacgaac caacattcca cgtgtggcca aaacagtttg tagatcgacg tgccatggtt27900ctatgtaaac acaaactcca gttggtcgtt cacaatcact gttaattgcc ataaccatgc27960aatctaaaag ttttaaaact gcaagaagac ctttcgtttg attttccgta ggtattaaat28020tcagactctg tagagaaatt cccactccac ctcgactttg taataccgtt cccacatcgc28080ctgtgatagc tcgaacagct ctcccaacag tgatggattc cgggtccatt aaataacaac28140tggccgttgc cccggtctct cgacctaaaa acatcataac cggtgtagcc gggacaattt28200tctgacatgc caacgctgtg aaaaataccc gacagacatc agtccatgta taaccatcat28260ttattccggg aataagagtt gcgattttag gcaggtttac gatttctgtt gtcacggtgg28320ccgccagtct taaaaagaat tggcaaagcg actctaattt accttcctct aacttagtta28380aataaaagtc ttcgtacttt aaagcagact gtagtccaag ggtagctaaa gcggggtatt28440gatctttcaa aaacggttct aatatagccc gacgaatttc gtccctccgc ccttcaattg28500cttggcggac tcggggagtt aaacagagaa ttggggaagt caaccacgtt tccatggaaa28560cggatcgtag gttaatacgg caatggataa gttctccaca acatcggtac actcgctcat28620cttgtcgcgt caccgcctta agttttgaga cgatagtgct aatatactcc attaattcca28680ccggtgtggt tgattcgggc ggaatgatgt attccttgta gccatgttga cataatcggt28740ttataatgtc atgaaccgta ttaaaaattc ttttgaactc cataacggat aacgtattta28800ggctccggaa taaaccttta aaccctaaac tcacagctga gttagttcta caatattgta28860gactccctta tatatggtta cgtacagcct gcccctcccc agtatataat atcacgcaaa28920acccacgcta tgttaaattc agtttatttt acatacatgc tttaataata acattcgttc28980catgtatttg taccccccca cacaaccccc tctaaccaaa tagttggcac gttataacct29040ccgaaccgtt ccatgcgtct tgtataacgc acagactctg atggaattgt tccaattaac29100gtatatgccg catacatgca ggataattgt gtgggaagtc cccgaaaatc gccggtccat29160tgatacaatc gctgtctagc caagttccaa tttactcctg taatttcgcc aatactacat29220cgagggcttg tcgggtcatt ggataactgc acaagcggca acgcccttgt gttatatggc29280tggtgggtat ttgcaacccc ttcagtcccc caggcggcat tttcagctcg tatgcgtcct29340aacaggaagc caataccacg accaaaacat tgttcgttta gttggcttaa tgcaagatgc29400agtcttacac cttctcgttg gcgtcgctgt gtatatacaa aaaccaagaa cacatgcttc29460agtccgtccg cggaaagatg taaatctttg tcaacgtccc aaaatacgca ggccgggatg29520ttggctgtga ccctgcgagt tgaagttttg tctgtacgtg cagcttcttg gggacctttg29580gccacggcgg ttatattgca taaattatcc tgaatggtat attccagcag ggacccaaaa29640aaacttataa atcgatgtgg aaatacatga cattgtacca tcgcacgtaa acactccgaa29700aaccttatga gccgcgtttc catacgactg catccatagg cagaaacaat tgctgttctg29760
ttggcatccg ctgcctgttt atccgtatat tcttctgccc ggcatgcggc gatgaaactt29820aatgacgtta catatgctct aagcccccca ccttctccaa cggtccaagg agccgtgcag29880gcattgaata ggtttcgtaa accctctagt agtacatcgg ggtcacgtcc agcctgtgta29940agtgtattag cttctccaat catgtcagat ggatgacgaa ggattaagac gattgaccca30000gcatgctcaa tgtccggacg aaaaaaatcg gttaatgaca cttgttggat tagctgtgtc30060gttgatttaa aattatttaa cgggagtcta atggtaactt gcgggttacc aattgaagtt30120ggatttattt gaatgttgtt catacgatta ataacaattg aacggggggt tacttgaata30180gacgcggttt ctgtacgttt tggtggtaca tgtatcggtt gtttgttcag acctccaaag30240cgagggccaa ttgttaaatc gcgactccaa tttccgaaga agcccggagc ataagtcata30300tgaagcccgt tccctatttg aataaaacgg ttatttccta aaagactgat attagttcca30360catagcgttt gttcgtttaa agtaaaatgc gagttggttg gttgactccc catagctgag30420gggttaaatt cacacaatgc aatcgtgacg tggtactatc tgaaatgttg cctggggtat30480gtgtacacat tatacagtcg tagtaccgtt tatataatgt taggtaggag gagcctataa30540aaatattttg attggcgtta aaaggttctt caacttaccg tgacgtcctt tttattaaca30600tgcgttttta ttgatgttac atttatgtct tttcattccg gacggatgta gctttttcat30660atcacgttat aaagttaagt cagcgtagaa tataccatgg aagaaccaat ttgttatgat30720acacaaaaac ttttggatga tttaagtaac ttgaaagtac aagaagcgga caacgaaaga30780ccatggtcac cagagaaaac agaaatcgcc agagttaagg tagttaagtt tttacgatct30840acccagaaaa ttccagctaa acattttatt cagatatggg aacccctgca ttctaatatc30900tgttttgtat attccaatac atttttggcg gaggctgctt tcacggccga aaatttaccc30960ggactgttgt tttggagact agatctagac tggacgatag aggagccagg taatagctta31020aaaattttaa cccagctatc aagtgtagta caagattccg agacgttaca tcgtttatcg31080gccaataaat tacgaacctc gtctaaattt ggacccgttt cgatacactt cattataacg31140gactggataa atatgtacga ggtcgcctta aaggatgcaa caacagccat tgaatcacca31200ttcactcacg ctcgtattgg aatgttggaa agcgccattg cagctttaac acaacataaa31260tttgcgatca tttacgatat gccatttgtt caagagggga ttcgtgtttt aacacaatat31320gcaggatggc ttcttccgtt taatgttatg tggaatcaga ttcaaaatag ctcactcact31380cctctaacac gagccctttt tataatctgt atgattgatg aatatctcac ggaaacgcca31440gtacatagca tatcagaatt atttgcagat actgtaaatt taattaaaga tgaggcgttc31500gtatccatcg aagaagcggt aacgaatcca cgaacggtgc acgagtcacg aatttcctca31560gctctggctt atcgagaccc ttatgttttt gagacatccc cgggaatgct tgctaggaga31620cttagattag acaatggtat atgggaaagc aacctcttat cgttgtccac ccccggaatt31680catattgagg cgctgttaca tttactaaac tccgacccgg aagcggaaac cacatctgga31740agtaatgtag cagaacacac ccgtggcatt tgggaaaagg ttcaggctag tacatcgcct31800agtatgttaa taagcaccct tgccgaatcc gggtttacaa gattttcatg caaattgcta31860cgtcggttta ttgctcacca cacactcgcc ggttttattc acggaagcgt tgtagcagac31920gagcatatta cagatttcca acaaacacta ggatgtctcg ctttagtggg tggactggca31980taccaattag tggaaacgta cgctcctact accgagtatg tgttaacata tacacggaca32040gtaaacgaga ccgaaaaacg gtatgaaacg ctattacccg ccttaggatt accaccggga32100ggcctgggac aaattatgcg gcgctgtttt gctccacgac cccttattga aagtatacaa32160gcgacacgcg taatactact taatgaaatt tcacatgcag aagctagaga ggcaacatat32220tttaagcaaa cacataatca atcctcaggt gcgttattac cacaagcagg acaaagtgcc32280gtacgcgaag ccgtactaac ctggtttgac ctacgtatgg attcaagatg gggtattact32340cccccggtgg atgtgggtat gacacctcct atttgtgttg atccaccggc tacagggttg32400gaagctgtca tgataacaga agcactaaag attgcatatc ctaccgaata taatcgctct32460agcgtgtttg tggaaccgtc gtttgtgcct tatattattg caacaagcac gcttgatgcc32520ctttcggcaa caatagcttt gtcttttgat acacggggaa tacagcaagc cttgtctatt32580cttcagtggg ctcgcgatta tggatccgga accgtgccca atgcagatgg atatcgcaca32640aaactatctg ctcttataac aatattagaa ccttttaccc gtacacaccc cccagtactt32700ttaccatctc acgtttctac tatagattcc cttatatgcg aacttcatcg gactgttggc32760attgccgttg acctgcttcc ccagcacgtc cgtcctttgg ttcctgaccg tccttctatt32820acaaatagcg tttttttagc aactctctat tatgatgaac tttacggtcg ttggacccga32880ctggataaaa catcgcaggc gttggttgaa aattttacat ccaacgcgtt agtggtttct32940cggtacatgt taatgttaca aaaatttttt gcgtgtcgtt tttatccaac gccagatctt33000caggctgttg gtatctgtaa cccaaaggtt gaacgcgatg aacaatttgg ggtatggcgt33060ttaaacgatc ttgctgatgc ggttggtcat attgttggga caatacaagg aatccgaacg33120caaatgagag tgggaatatc cagcctgcgc acaattatgg ccgatgcttc ctcagccctt33180agggaatgtg aaaatttaat gactaaaacc tccacttctg ctattgggcc tcttttttca33240
acgatggctt cccggtatgc acggtttaca caggatcaaa tggacatttt aatgcgtgtt33300gacaaactaa caacaggaga aaatataccc ggtcttgcaa atgtagagat ttttttaaat33360aggtgggaac gaatagcaac agcttgtagg catgccacgg cagtcccgtc ggccgaatct33420attgcaaccg tgtgtaatga attgaggcgc ggtttaaaaa atatacaaga ggatcgtgta33480aatgccccaa cctcatatat gagtcacgcc cgaaatctgg aagatcacaa ggcagcagtt33540tcattcgtta tggactccag gcaacagttt attgtggatt ctggacctca gatgggcgcg33600gttttaactt cacaatgtaa tataggaaca tgggagaatg taaatgcaac gtttttacac33660gacaacgtta aaataacgac aacggtcaga gacgtaattt cagaggctcc gacgctgata33720ataggacaaa gatggcttcg tccagatgag attttatcta atgtagattt gcgtcttggc33780gtacccggga atacaagtgg gagtgaccct taatataaaa caggcgtgtt tatgtacatt33840aaagtatttg tggtttttat tgactgggcg tttcgtttgt ataacgctgt tgttgctagt33900attttcataa cctcctaggt ttttggagct acacgtgctt attcaacgct ctttgggatt33960tgaatcatcg taaacgtagc gtccctacca gttgagcgcg taattttcgt aagcaataaa34020atggatataa ttccgcctat agctgtcact gttgcgggag tgggaagccg taatcaattt34080gacggtgccc tgggaccggc gtcaggtctg tcatgtttaa gaacatcttt atcgtttttg34140catatgacat atgcgcatgg aattaatgca accctgtcat cagacatgat tgatggatgt34200ttacaagagg gtgcagcatg gactacggat ctgtctaata tggggagggg tgtcccagat34260atgtgtgctc ttgttgatct ccccaatcga atttcatata ttaaactggg ggacactacc34320agtacgtgct gcgttttgtc tagaatatac ggcgatagcc atttttttac cgttccagac34380gagggtttta tgtgcacaca aattcccgct agagcgtttt tcgatgatgt gtggatggga34440cgtgaagagt cgtatacaat tataactgta gactcaacgg gaatggccat ctatcgtcag34500ggaaacatat cttttatttt tgatccacat ggccatggga ctataggaca ggctgtagtt34560gttcgggtga ataccacgga tgtgtactct tatatcgcat cggagtatac ccaccgcccc34620gataacgtag aatcccaatg ggccgctgca ttagtttttt ttgtcaccgc aaacgacggt34680cccgtaagcg aagaagcgct atcttcggca gtaacgctta tatacggaag ctgtgataca34740tattttacag atgaacaata ttgcgaaaaa ctggttacag ctcaacatcc gttgcttctt34800tcacctccta attccacgac aattgtgctt aataaatcgt ctatagtacc tcttcaccaa34860aacgttggtg aaagtgtatc cttggaagca accctacatt caacgttaac caacacggtt34920gcactggacc ctagatgtag ttacagcgag gttgatcctt ggcatgcggt tctagaaaca34980acctcgactg ggtctggcgt tttggattgt cgtcgtagac gccgtccttc atggactcct35040ccttcaagcg aggaaaattt agcttgtatc gacgatggct tggtaaataa tacacattcc35100acggataatt tacataaacc cgctaaaaag gttctcaaat ttaaaccaac tgtagacgtg35160ccggataaaa cacaagtggc acatgtatta ccccgcctac gagaagttgc taacacccca35220gacgttgtgt taaatgtatc caatgtagat acgcctgaat ccagtcccac tttttcacgg35280aacatgaatg taggaagcag tttgaaagat cggaagccat ttctatttga acagagtggt35340gatgtcaaca tggttgtcga aaaactacta caacatgggc atgaaattag caatggatac35400gtacaaaatg cggtgggtac gttggatact gttattaccg gtcatacaaa tgttcccatt35460tgggtaacaa ggcccttggt catgccagac gaaaaggatc cattggagct ttttattaac35520ctcaccattt tgcgtttaac gggatttgtg gtggaaaatg gaacacgtac acatcatggt35580gctacaagcg ttgtatcaga ctttataggt ccccttgggg aaattttaac aggatttccc35640tccgccgcgg aacttatacg cgttacaagt ttgatattaa caaacatgcc gggggcggaa35700tatgctatta aaactgttct ccggaaaaaa tgtacaattg gcatgctcat tatcgctaag35760tttggtctag ttgccatgcg ggttcaggat acaaccggcg ctttacatgc cgaactagat35820gtgttagaag cggatctagg aggttcgtcg cccatagacc tctattctag actgtcgaca35880ggtcttataa gtatactaaa ttcgcctatt atttctcatc ccggactttt tgccgagctt35940attccaaccc gtacagggtc cctgtctgaa cgaatacgtc ttctttgtga attagtctcg36000gcccgggaga cacgctatat gcgtgaacac accgcgcttg tttctagtgt aaaggcttta36060gagaatgcat tacggtctac ccgcaataaa attgatgcca ttcaaatacc agaagttccc36120caggaacccc cggaagaaac cgacattcca cccgaagagt taattcggcg tgtatatgag36180atacgatccg aagttacaat gctattgacc tcggctgtta cagaatactt cacccgcgga36240gtgttatata gcacacgggc cttgatcgct gaacaatccc ctaggcgttt tcgggtcgcg36300accgcaagta cggcacccat tcaacggctt ttagattctc ttccggaatt cgacgctaaa36360ttaacggcaa tcatatcgtc cctgtctata caccctcctc ctgagactat acaaaatctc36420cccgtcgtat ctctgttaaa agagcttatt aaagaagggg aagatttaaa cacagacacg36480gctctcgtat cgtggttatc tgtagtcggg gaagctcaaa ccgcaggtta cttatccaga36540cgagagttcg atgaattatc acgtacaatt aaaaccatta atacacgcgc aacgcaacgg36600gcttccgcgg aagcagagtt gtcttgcttt aatacgctaa gcgcggccgt agaccaagcc36660gtaaaggact atgaaacata taacaatggt gaggtcaagt atcctgaaat aacacgggat36720
gatttattag caacaattgt acgtgctaca gacgatttgg tgcgacagat aaaaatttta36780agtgatccaa tgatccaatc cggtttacaa ccttcgatta aaagacgatt ggaaacaagg36840cttaaagagg ttcagacgta tgcaaacgag gcccgaacca cacaggacac aataaagagt36900cgaaaacagg cggcatataa taaactcggg gggttacttc gcccggtaac cggttttgtg36960ggacttaggg ctgcagtaga tttattaccg gaacttgctt ctgagttaga tgtccaagga37020gccctggtaa atctcaggac caaagtctta gaggcgccgg tagagatccg ttctcaactt37080acgggtgatt tctgggcgtt atttaaccaa tatcgagaca ttttagaaca tcccggaaac37140gcacgcacat ctgtcttagg aggactggga gcttgtttta cagctattat cgaaattgtg37200ccgataccta cggagtatag accatcattg cttgcgtttt ttggtgacgt ggcagatgtg37260cttgcatccg acatcgcgac cgtatctact aacccggaaa gtgagtccgc cataaacgct37320gttgttgcaa ctcttagtaa agcgacgtta gtttcatcta cagtgccagc cttatccttt37380gtgttgtcgt tatataaaaa atatcaggct ttacaacaag aaattacgaa tacccataag37440ttgactgaat tacaaaaaca acttggagat gacttctcca ccctagctgt ctcatctgga37500cacttgaagt ttatatcatc ttcaaatgta gatgattatg aaataaacga tgcgatatta37560tcaatacaaa caaatgtgca cgccctgatg gatacggtta aacttgttga agttgaactg37620caaaagctac ccccccattg tattgctggg acatctacct tatctcgagt agtaaaggat37680cttcataaac tcgtcacaat ggcacatgag aagaaggaac aggcaaaagt gttaattacc37740gattgtgaac gtgcacataa acaacaaacg actcgggttt tgtatgagcg ttggacacgt37800gatattatag catgtctgga ggcaatggaa acgcgccatg tatttaacgg gacagaactg37860gcacggttgc gagatatggc cgctgcggga gggtttgata tacacgcagt ttacccacaa37920gcacgtcagg ttgtagcggc atgtgaaact acagccgtta cggcattaga tactgtgttt37980cgccacaatc cacatacccc cgaaaataca aatattcccc cacctttggc tttgttaaga38040gggttaacat ggtttgatga tttttcgatt acggctcccg tattcaccgt tatgtttcca38100ggtgttagta ttgaaggact ccttctgctt atgcgtattc gcgcggttgt gttattatcc38160gccgatacgt ctattaatgg aatacctaac taccgagata tgatattacg aacctcgggg38220gatctattac aaatacccgc attggctggg tatgttgatt tttacacacg gtcttatgat38280cagtttataa ccgaaagtgt aacgttaagt gaacttagag cagacatcag acaggctgcc38340ggggctaaac ttacagaagc aaataaggct ttggaggaag taactcatgt tcgggcacac38400gaaacggcta aacttgcact taaagaaggt gtcttcatta cattaccaag cgaaggttta38460ttgattcggg ctatagagta ttttacaact ttcgatcata aacgatttat aggaacggca38520tatgaaagag ttttacaaac aatggtagac cgcgatctaa aggaggccaa cgcagagctt38580gcacagtttc gtatggtgtg tcaggcaaca aagaaccgtg caatacaaat tttacaaaac38640attgttgata ctgctaatgc cactgagcaa caagaagacg tggatttcac taacctgaag38700acgttattaa aactaacccc ccctcccaaa acaattgcat tggccattga tagatctact38760tctgttcagg acattgtcac gcagtttgca ttgctgttag ggcgtctgga agaagaaact38820ggtacgttgg acattcaggc ggttgactgg atgtaccaag ctcgcaatat tattgactcc38880catccactaa gtgtgcgtat agacggtacc ggccccctgc atacttataa agatagggtg38940gataaacttt atgcgttacg gactaaatta gatctcctac gacgacgaat agaaaccggt39000gaggttacgt gggacgatgc atggacaaca tttaaaagag aaacggggga tatgttggca39060tcgggggaca cgtacgctac ttccgtagat agtataaagg cactccaggc atcggcgtct39120gtggttgaca tgctttgttc cgaacccgaa ttttttttat tgcctgtgga aacgaaaaac39180cgtctccaaa aaaagcaaca agaacgtaaa acggcgttgg atgttgtgtt gcaaaaacaa39240agacagtttg aagagaccgc gtctcgctta cgagctttaa ttgaacgtat tccaacggag39300agtgaccatg acgttcttcg tatgttatta catgatttcg atcaatttac acatttgcct39360atatggataa aaacacagta tatgacattt cgaaatttac tcatggtacg gttaggcttg39420tatgcaagtt atgctgagat ttttccaccc gcgtctccaa acggagtgtt tgctcctatt39480cccgccatgt cgggtgtatg tctagaagac caatcccgat gcattcgcgc gcgggtggcc39540gcgtttatgg gggaggcgtc tgtggtgcaa acgtttaggg aagccagatc ttctatagac39600gctttgtttg gaaaaaattt aaccttttac ttggatactg atggggttcc acttcgatat39660agagtgtgtt ataaatcagt tggggttaaa cttggaacca tgctatgcag tcagggtgga39720ttatctttac gaccggcact tcccgatgaa ggtattgtgg aagaaactac actatcggca39780ttacgcgtgg ccaatgaggt caatgagcta cgcattgaat acgaatccgc tataaaatcc39840gggttttctg ccttttccac ctttgttagg catcgccacg ccgaatgggg taaaaccaac39900gcacgcagag ccattgcaga gatatacgcc ggccttataa caacaacatt gacacgacaa39960tacggggttc attgggacaa gcttatttat tcttttgaaa aacaccacct aacttctgta40020atgggcaatg gactaactaa accaatccag agaaggggtg atgtacgtgt attagagtta40080accctatctg atattgtaac tattttggtt gccacaaccc cggtacatct tctcaatttt40140gctagattgg atttaattaa acagcatgag tatatggccc gtaccctcag acccgtaatc40200
gaggccgcat ttagaggtcg tttactcgtt cgctcattgg atggagaccc gaaaggcaat40260gcccgggcct tttttaatgc cgccccatcc aaacataaac tcccgttggc tcttggatca40320aaccaggatc ctaccggcgg gagaatattt gcatttcgga tggcagattg gaaacttgtt40380aaaatgccac agaaaataac ggatcctttt gcgccatggc aactttcccc cccccccggg40440gtaaaggcca atgtcgatgc agttacccgt ataatggcaa cagatcgtct tgcgaccatt40500actgtacttg ggcgcatgtg tctcccgcca atttccttag tgtcaatgtg gaatacgctg40560caaccggagg aattcgcata cagaacacaa gatgatgtgg acattatagt tgatgcgaga40620ctggatttgt catccacgct taatgcaaga tttgataccg ctcccagcaa taccacgtta40680gagtggaata cagaccgtaa agtaattaca gatgcttata ttcaaaccgg ggcaacgaca40740gtttttacag taacgggggc ggcaccaact cacgtttcta atgtaacagc gtttgacata40800gcaactacgg ctattttatt tggggctcct ttggttattg ccatggaact tacatccgtt40860ttttcacaaa attccggact tactttgggg ttaaaattat tcgattcccg gcatatggct40920acagattcgg gtatatcctc agccgtatct cccgatattg tttcttgggg gttacgttta40980ctgcatatgg atccccaccc aattgaaaat gcatgtttaa ttgtccaact agaaaaactg41040tccgcgctca ttgcaaacaa acctcttaca aacaatcccc cgtgtttact gctattggac41100gaacatatga atccctctta tgttttatgg gaacgaaaag actcgattcc agctccggat41160tatgtggtct tttgggggcc agaatctctt attgatttgc cgtacatcga ctccgatgag41220gactctttcc cctcgtgtcc cgatgatcca ttttactcgc aaattattgc cggttatgcg41280ccccaaggcc ccccaaacct cgacacaact gatttttacc caacggagcc actatttaag41340tctcccgttc aagttgttag aagttccaaa tgtaaaaaaa tgcccgtcca gcccgtccag41400cccgcgcagc ccgtccagcc cgtccagccc gcgcagcccg tccagcccgc gcagcccata41460gaaccgggca cacaaatagt ggtacaaaat tttaagaaac cccaaagcgt aaaaacaacc41520cttagccaaa aagatattcc cttgtatgtg gaaactgaat cagaaacggc tgtgcttata41580cctaagcaat taaccacctc cattaaaaca accgtttgta aaagtattac cccaccaaat41640aaccaattgt cggattggaa aaataatcca cagcaaaacc aaacgttaaa ccaagcgttc41700aataaaccaa tacttgagat tacctccatt ccgacagatg actcgatatc ttaccggact41760tggattgaaa aatcaaatca aacacaaaaa cggcatcaaa atgaccctcg aatgtataac41820tccaaaacag tattccaccc tgtaaataac caattacctt cttgggttga cacggcagcc41880gatgcccccc aaacggacct attgacaaac tataaaacaa gacagccgtc gccaaacttt41940ccgcgggacg tacacacatg gggcgtatct tctaacccgt ttaactcacc gaacagagac42000ctatatgaaa gtgattttag tgaaccttct gacggctata gcagtgagag tgaaaattct42060atcgtactaa gtctcgacga acatcggtca tgtcgcgttc ctaggcacgt acgtgttgtt42120aatgccgatg tagtcaccgg tcgacgttat gtccgaggga ccgccttggg agcactggcc42180ctgttaagcc aggcatgtcg gcgtatgatc gacaacgtta gatatacacg taaactttta42240atggaccaca cggaagatat atttcaaggc ctggggtatg ttaaattgtt attagatgga42300acatatatat aaagtagcgc ctattaaaga aaaaaaaaaa caacgattat tttctgtgta42360tttttattta caccctacga cttcttgaag cgtttccaga ttgtcccgtg tgggacaagg42420tctgtccctt acccccctgg ggggtatttt gggttggggg cggggtagac tgtggcacgc42480cttgggccgc gggcggtgat ccggttgttg gctggacagt gcttgactgt gctccctgtt42540gcggttgttg tccagaagac cccgacacca cgtgttgctg ttgtccaacg gatgccgacg42600tcgtttgagg tggggggtgt tgcggggatg atcccgaaaa cgccaacgcg gcgggctgtt42660gtaaagcaga ctgatcggcg ctctgtgttt tttgcggcaa tatagtaggc cccgagattc42720ccaaactcat ggatggattt gggggttgtg gtcgtataat acgcgggtta aacgtacgtt42780ttaagccaac cgttggtctt aaccatgtca tagggtcagt ctcggcaaac atggccgttc42840ggcgtatcgt atttgcatta tggttagcgc gtgcacgcgc ggcactggcc gcggctccca42900cggtgtaaat gcttctggca tcagcgatgt ccacacggtg accaggttgc aaaggtccac42960tggcgtttaa aagtcgtatt aaagcaacgg gggtgtaagc cgcaattgct tccaccgaaa43020atgtggtggg gttgctggga tcaaagacta cacgagacga tgcgggttgt gtcatcgttt43080attagtttac gggacaatcg ataacagcat acacgtacat ctgcgcagga tatgtacgga43140aaggcaattt atttccagaa aagcaccgcc cctaatacaa ctaccagtac aattacaacg43200aacagggcat atgtcacgtt agctacgggt agagcaagtt tccagacacg cgtagtttgg43260gtatcgggta acgcaggttt aatgtcactt tgcatttgaa cagacgtgtt tggacttccg43320ttctcgggtg gggatctgaa tgaaggccgc cagcgtatat attcatccaa attattgcca43380gtttccttat acatgtatgc atccgtggcg cgggccataa gtttaatggt gcgagatgga43440tcttccggtc ccataaaacg aaaggataac tgaacatatg gcattcgcac aaagcagttc43500acccacatta aagcctggag aggtcggcgg tcaatacccc cacctcgttt aattgattcc43560aaagcagata ggttgatacc ggtacttaac gttgaactaa gaatcacgtt attactgtca43620atggacactt cagccactgg tgcgttagtc ggacgaaaaa aaaaaccttg aaatagcaca43680
gacacccccg tattttgaat ttttatgtaa gggtcacaat ctacttgcgc ccaattcgcc43740attaaacgca taatatactc taccggaaag gcttcggata cgttgtcttc gccgttaaac43800tgaaaaacac aacgggcggg ggggcgttgt ggatcaaata ttggaagatc cccatcgcaa43860cattgaagag cgcttggtac caccaaccga atacgttgta aaagattatc tccgcaaccc43920ctcctgcgtt cactccgtac atacgttctc cgtgacatat tgatctaagg ttgcaaacca43980aggcacacgc gtgaagtatt tagaccattt atcgtgggat ataggaggag tttggagtga44040tccaccccct gacgacttat taatgcgttt attttcccca tgtattaagc atccttcaat44100atttcatgca aatctagaaa tttggccatg actcccgcaa agcgttcacg gcgacgggtc44160acgctggcac tatgttcaca tggaacaaca taagcagatt tttctgaatc gttactttct44220ttatgtttta aaacggacgc caggcgactg gtaaatgata tataatttaa ttgagcgtca44280gttgtaggta gaattgcttc tatttccggg ggaattaaat tttcaaacca aacggaaaga44340gtaaaggtgc tatcagcagg aaaatacttt gactccagtg catcgatatt taatagatta44400acatcggtgt ctgtaattaa atcgcgggcc ctcatcccag agatggatcg ggtagaatca44460gaagaaccca tggatggatt cgaatcgccc gtattctccg aaaatacatc ttctaattcc44520ggatggtgtt ccgacgcatt ttccgattcg tacatcgctt ataatccagc ccttctgcta44580aaaaacgatt tgttattttc agaattgtta tttgcctccc acttaataaa tgttccccgt44640gcaatagaaa acaacgtcac ttatgaggcc tcttcggcgg taggtgtgga taatgaaatg44700acctcaagta ccactgaatt tatagaagaa attggagacg ttttggcgtt agacagagcc44760tgtttggtct gtagaacgct tgatttgtat aaacgtaaat ttggactgac accggaatgg44820gttgcggact acgccatgtt atgtatgaaa agtctggcat ccccgccctg tgcagttgtc44880acttttagcg ctgcctttga atttgtgtat cttatggatc gttactacct gcgccgttat44940aacgttactt tggttgggtc ctttgccagg cgcacgcttt ccctgttaga tatacaaaga45000catttttttt tgcatgtatg ttttcgtacc gatggagggt taccaggtat acgaccgccc45060cccggtaagg aaatggccaa caaagtaaga tattccaatt actccttttt tgtacaggcg45120gtagttaggg ctgcattact atcgatcagc acgtctcgtt tagacgaaac cgaaacgcgt45180aagtcatttt actttaatca ggacggactg actggaggcc ctcaaccttt agcggccgcc45240ttggctaatt ggaaagattg cgcgcggatg gttgactgtt catcatcgga acatcgcaca45300agtgggatga ttacctgcgc ggaacgtgca ttaaaagagg atatagagtt tgaagatata45360ttaatagaca aacttaaaaa atcgtcttac gtagaagcag cttggggtta cgcagacttg45420gctttattat tactgagtgg ggttgctact tggaatgtag acgagcgtac aaattgtgct45480atagaaactc gcgttggatg tgttaaatca tactggcagg cgaaccggat tgaaaactcc45540agggacgttc caaaacaatt ttccaaattt acgagcgagg atgcctgtcc cgaagtagca45600tttgggccta ttttgttaac taccttaaaa aacgcaaagt gccgtggtcg cacgaatacc45660gaatgcatgt tatgttgttt attaaccata gggcactatt ggatcgcttt gcggcagttt45720aaaagggata tattagcata ctcagcaaat aacacaagtt tatttgactg tatcgaacct45780gtaatcaatg catggagcct agataacccc attaaactta aatttccatt taatgatgag45840ggtcgattca taaccattgt aaaagcagca ggttccgagg ccgtatataa acatttattt45900tgcgatctcc tatgcgctct ctcggaatta cagacaaacc ctaaaatttt atttgcccat45960cctacaaccg cggataagga agtgttggag ttatataaag cccaactggc tgcacaaaac46020agatttgaag gtcgtgtatg tgctggcctg tggacattgg cgtatgcatt taaagcctac46080cagatttttc cacgcaaacc aaccgccaat gccgcattca tacgagatgg aggacttatg46140cttcgacgac atgcaatatc gctggtctcc ctcgaacaca ccctatcgaa gtatgtctag46200gcgatataaa tccgtatctc ggagcgggcc ttcgatgcgt gtacgctcca gaacgccatg46260ccgccgtcaa accattcgag gaaaacttat gtcaaaggag cggtctgtgt accgccatta46320ttttaattac atcgcaaggt cccccccaga agaactagct accgttagag gcttaatcgt46380gccaattatt aagacgaccc ctgtcaccct tccgtttaac ttgggtcaga cagtggcgga46440taactgcctg tcgttatccg gaatgggtta tcatttaggt ctcggaggtt attgtccgac46500atgcactgca tctggagaac cgcgtctatg tcgaaccgat cgggcggctc tgatactagc46560atatgttcag cagcttaaca acatatacga atatcgtgtg tttcttgcat ccattttggc46620gctatcagac cgagccaaca tgcaagcagc gtccgctgaa cccctattgt cgagcgtatt46680ggcacaaccg gaattatttt ttatgtatca tattatgagg gaggggggca tgcgagatat46740acgcgtactt ttttatcgtg atggagatgc cggagggttt atgatgtatg ttatatttcc46800ggggaaatct gttcacctcc attacagact aatcgatcat atacaggccg cgtgtcgggg46860gtataaaata gtcgcacacg tttggcagac aacattttta ctgtcggtat gtcgcaaccc46920agaacaacaa acagagactg tggtgccatc cattggaaca tcggacgttt actgtaaaat46980gtgtgacctt aactttgatg gagaattgct tttggaatac aaaagactct acgcattatt47040tgatgacttt gttcctcctc ggtgatttca gcttcagtgt tcattttatt atcccagcgc47100ggggcgtgta tacaaacaaa gcctgccgcc tgcaagcggt ttagcatttt aacgttaaca47160
actcgtgtct ctggaataaa acgttttaaa agccgttctg tgagtttagt gtcgtttcca47220aataacgcct taaaagttac actcgccgtc ccaatgagat gagaaaaata atagtcaatg47280tttaaagaca gcccgtgtga tgttacgtga atgggatctt ccgctaagtc agatattatt47340aacttacgct ttgcttcccc acaccgttta cctgcggtat tctgtaaagg atctccacgt47400agcaaagcta cactttttgc atcagcctcc acttcgtctg tgggggccac aataacataa47460gggatgcgtt ctcgaacggt tgggatttga ccctgtctca ttactaattt ataatatact47520gttaagtgag ccaagcgacg gtttatgtag gcggatggtg gacgactaag ctcggccgtc47580ataacaaact tattaatatc caatttgggt gatgtaatct ggcgatgtgc atctgcaatt47640atgcgtccaa acccggccat cccagacggc atggcccgtc tattccattc agcaatggaa47700acacacgacg cctccgccgc agcacgcgag acggtgtcgt catataacaa cagttctaca47760agtttgcggg cataatcgtt aataaattga cagttgtttt ttctaaccaa gtcgactccc47820ttcattaaaa cctttccgcc gtaaattacc ccaatgtact ttttctttgt tataagtaaa47880agttttataa aagttttttc acactccaac tttataggag gacaaaacag agccgttgaa47940attatatgtg ccattttctc gccgatttta gctatcccct caacaccaac acccttgaat48000cggataaaca cagaatccgt atctccatat ataaccttta cctcgtacgc tttttgggag48060agaacgctac tttcaatgtc tggaaacgct gtaataaaac gttcaaatgc ggcccagtta48120ttatgaatat aatctctggt acttaataac atttgacggc caattgtagt gacagtggcc48180gctacgtata aacatggcag aaatccctgc gcaactccag taaaaccgta cacggaatta48240caaactactt ttatcgcggc ttgttgtttg tctaataaca ctgcttcatc tgaagaactt48300ccgggtatgc gcgctctaat agccttgcgc atagccaacc agtcttttaa aagaacaccc48360agcagacttt ctcgaacgtt agagcgcaca aaaaaaagac gttttcctcc aactgtaaag48420gtggcataat cggatggatt caaacgttta accgtctcaa aatttaacgt tagcgtggta48480aaacataagt tatgggcctg aattatactt ggatataaac ttgcaaaatc caatacgacc48540accggatcga tataaaatcc cgtatcaggg tcaaaaaccc tggctccttt atatcctaca48600tttcgcccac ttgacgtacc agtgggagaa acgctctcgt cttcatccat ctcttcctca48660acatccccga catcgggaat aacatcctta tattcaaaag tagctgggta tcccccatcg48720ggtaaaataa atcctcgaga cgaagccagt cctaataaac aagtgtaaat cctaacctgc48780tgtccgtcgt aaatagcctt ggttaaagta attctagcta gccttgcaac cgcggataac48840tcaaggtgtg gtaaatattt aaaaaacagt ttccccacaa gagccgagtc ttgtatacaa48900tattcaccaa taattcctcg tgtattcggt ccactagcgt aatatcccgg aatgtctttg48960tagggcaaat ctctcttgga ctcatttaga gcttcacgtg caaccgaatc taatttataa49020ctcgagagtt ttaatttttc agttgcaatt gcatacatat ccagagatat gagaccgttg49080atctttacct tgcttcgtcg ctgaaatccg gatttgccaa catcccatat cttaaacaga49140cccccacggt ttatactgcc ataaccatca agcttgagac tgtatataga attaagtttc49200tccataataa acgcccaatc aaaattaaca atgttataac ctgtggcaaa ctcgggagcg49260tactgtttta cgagggtcat aaatgcaatt aatagctcga attcactatc aaactccagc49320acagtcggct ccggtaaccc cgcgtccttc atttcttgta catacctttg tggtaagtca49380caagagccaa gggaaaacag taaaatgtgt tctaaagact gtcgagggat tgaatataat49440agacaagaaa tttggattac aagatcctcc aaatgtgttg catcgggaaa cgccagctca49500ttagatcctc ctgatttaca ttcaatatcg aaacataaca acttgtagtc aggccatgag49560tcatcgtttg gtatagcctg cagattatcc gacatgcagt caatttcaac gtcgcttaac49620gttaattggc gacttgccgg tcgaactcga acacgttccc catcaactcc aggttttagt49680tgataccaac caaaactaac aaagccggga ttatccatta gaaaacgagt ggtagcgtct49740acccgacctt catacttttt caactccggg tgaaagttat cacaaagata atttgtaaat49800ttagatgagg gagaatacac cctgtaaaac gcacatggct gtgtatcgta gtaataaaca49860tctgtgcgct caataacctc aacgcgaaag ctttctggag atgcgctttt aaacgaggta49920ccatgaaaag cgttcttgtc tccatttaac gttgcatcat tttgtgttat catagaactg49980cgtaaacact cggcaagtaa tacagataac tcgctacagg aacgtatgcc acaagcggta50040tccacctcgg ctttgtttat ataaaaatat tgacagatgc cgtatacatg aactgccacc50100ctttttccac atcgggacat gccaagtaaa gtaataacgg taccaagcgg tcgtgttgca50160gttgcaaacc gggatacatc tccattagac gcggcttctg ttgtttcgac aatatcatat50220acatggaatg tgttaaagcg ggggtcaaac ttatccccac gaaagtcgat ttccccccaa50280atattcacgc gtctaggcca ggggctggaa caacgaaaat ccagaatcgg aacttctttt50340ccattacagt aaactttagg cggtcgacta agtgtaccga cgtgaacccc ctttcgttct50400tccatgggca catcttcatc taaacattta ggggccaaaa attgaaacga tgacatggta50460gttttgtaac tatgaagaaa ttctctgtta ctaccgcgcc cggttcttgg gttatattta50520atccctgatg cttgggttaa aaagggatta caaaaccccg ttctgatcgc cattttatgt50580taacgattga taatcttgta aaaagccagt gttactgagt aacacaaccc cacgcccttc50640
taatacataa agtgtaatca cgtgatttgt tgtggtttcc gcatatgtaa tacccgttta50700aaagcctctc ttcttaatgt atcgacagac tgggttttgg gtggtcattt gaccctgcca50760acaacccccc attattacga gtacttcacc aaaatggaaa atactcagaa gactgtgaca50820gtgcccacgg ggcccctggg ttacgtttat gcgtgccggg ttgaagattt ggatctggag50880gaaatttcat ttttggccgc tcgtagcacg gactctgatt tggctttatt acctttgatg50940cgtaatttga ccgtggaaaa aacttttaca tccagcctgg cggtggtttc tggagcacgc51000actacgggtc ttgccggagc tggtattacc ttaaaactca ctaccagtca tttctatcca51060tctgtctttg tctttcacgg aggcaaacac gttttaccca gctctgcggc cccaaatctc51120acacgcgcgt gtaacgcggc tcgagaacgg tttgggtttt cacgctgcca agggcctcct51180gttgacggtg ctgttgagac gaccggcgct gagatatgca cccgccttgg attagagcca51240gaaaatacaa tattatactt ggtggtcacg gcattgttta aggaagccgt atttatgtgc51300aacgtgtttc tgcattatgg aggactcgat attgttcata ttaaccatgg ggatgttata51360cgtataccgt tatttccggt acaacttttc atgcccgatg ttaaccgtct ggtacccgac51420ccattcaaca ctcatcacag gtctatcgga gagggttttg tatacccaac acccttttat51480aacaccgggt tgtgccattt aatacatgac tgtgttattg ctcccatggc cgttgccttg51540cgcgtcagaa atgtaactgc cgtcgcccga ggagcggccc accttgcttt tgatgaaaat51600cacgaggggg cagtactccc ccctgacatt acgtacacgt attttcagtc ctcttcaagt51660ggaaccacta ccgcccgtgg agcgcgtcga aacgatgtca actccacgtc taagcctagc51720ccatcggggg ggtttgaaag acggttggcg tctattatgg ccgctgacac agccttgcac51780gcagaagtta tattcaacac tggaatttac gaagaaactc caacagatat caaagaatgg51840ccaatgttta taggcatgga gggcactttg ccaaggctaa acgctctggg gtcatatacc51900gctcgtgtgg ccggggtcat tggtgcgatg gttttcagcc caaattctgc gttgtatcta51960actgaggtgg aggatagcgg gatgaccgaa gccaaggatg ggggaccggg tccatcattt52020aatcgatttt accagtttgc cggacctcat ttagctgcga atccccaaac agatcgagat52080ggccacgttc tatccagtca gtctacgggt tcatcaaaca cagagtttag cgtggattat52140ttggcactca tttgtggatt tggagcaccc ctgttggcgc gactgctttt ttatctagaa52200cgctgtgacg ctggtgcgtt tacagggggt cacggggatg cgttaaaata tgttacgggg52260acctttgact ctgaaattcc atgtagttta tgtgaaaaac acacgcggcc ggtatgcgct52320cacacaacag tacaccgact tagacaacgc atgccgcgat ttggacaagc cacccgtcaa52380cctattgggg tgtttggaac aatgaacagc caatatagcg actgcgatcc tctaggaaac52440tatgctccat atttaatcct tcgaaaaccc ggggatcaaa cggaagcagc aaaggcaacc52500atgcaggaca cttatagggc tacactagaa cgcttgttta tcgatctaga acaagagcga52560ctactggatc gcggtgcccc atgttcttcc gagggactat cgtctgtcat tgtggatcat52620ccaacgtttc gtcgcatatt agacacactg cgtgcgcgta tagaacagac aacaacacaa52680tttatgaaag tgttggttga gacccgcgat tataagatcc gtgaaggatt atccgaagcc52740acccattcaa tggcgttaac gtttgatcca tactcaggag cattttgtcc cattaccaat52800tttttagtta aacgaacaca cctagccgtg gtacaagact tagcattaag ccagtgtcat52860tgtgtatttt acggacagca agttgagggg cggaactttc gtaaccaatt ccaacctgtt52920ttgcggcggc gttttgttga cctgtttaat ggggggttta tatcaacacg ctctataacc52980gtaacattat ctgaaggtcc tgtatccgcc ccaaatccga cattgggaca agacgcgccc53040gcggggcgta cctttgatgg ggatttagcg cgcgtgagcg tggaagttat tcgggatata53100cgagttaaaa atagggtcgt tttttcaggt aactgtacaa atctctctga ggcagcccgg53160gcaaggcttg taggccttgc aagtgcgtac caacgccaag aaaaaagagt ggatatgtta53220cacggggccc tagggttttt gcttaaacag tttcacggcc tgttatttcc tcggggtatg53280ccaccaaaca gtaaatcccc caacccgcag tggttttgga ccctgttaca acgcaaccag53340atgccggcag ataaacttac acacgaagag attaccacta ttgcagctgt taaacggttt53400accgaggaat atgcagcact aaactttatt aatctacccc caacctgcat aggagaatta53460gcccagtttt atatggcaaa tcttattctt aaatactgcg atcattcaca gtaccttata53520aataccttaa cttctataat tacgggtgcc aggcgcccgc gtgacccatc atccgttttg53580cattggattc gtaaagatgt cacgtccgcc gcggacatag aaacccaagc aaaggcgctt53640cttgaaaaaa cggaaaactt accggaatta tggactacgg cttttacttc aactcattta53700gtccgcgcgg ccatgaatca acgtcccatg gtcgttttag gaataagcat tagtaaatat53760cacggagcgg caggaaacaa ccgcgtcttt caggcaggga attggagcgg tttaaacggg53820ggtaaaaatg tatgcccgct atttacattt gatcgcactc gccgttttat aatagcatgt53880cctagaggag gttttatctg ccccgtaaca ggtccctcgt cgggaaatcg agaaaccacc53940ctatccgacc aagttcgcgg tataattgtc agtggcgggg ccatggttca attagccata54000tacgccacgg ttgtgcgtgc agtgggcgct cgagcacaac atatggcatt tgacgactgg54060ttaagtctta cagacgatga gtttttagcc agagacttgg aggagttaca cgaccagatt54120
atccaaaccc tggaaacgcc ctggaccgta gaaggcgctc tagaagcagt aaagattcta54180gatgaaaaaa cgacagcggg agatggggaa acccccacaa acctagcatt taattttgat54240tcttgtgaac caagccatga caccacatct aacgtattaa acatttcagg gtcaactgtc54300cctggtctta aacgaccccc cgaagatgac gaactctttg atcttagtgg tattcccata54360aaacatggga acattacaat ggaaatgatt taacctccct ctttatccaa ttaaagccca54420cacgcgggtg agtgtacgta ataaacaagt caatattaca tattctgttg tgttttcttt54480tttgcgtgta gtccttaccc atatgacctg taatatagtg tgtctccaac cattcagctt54540acagtccagt ggacagtaac agcccgataa catggaattg gatattaatc gaacattgtt54600ggttctactg ggtcaagttt atacgtacat ctttcaggtt gaactgctac gtcgatgtga54660tccaagggtg gcgtgtcgct ttttatatcg gttagcggct aactgtttga cagttcgtta54720tttattaaag ctgtttctcc ggggatttaa tacccagcta aaatttggaa acactcccac54780ggtttgtgca ctgcattggg cattatgtta tgtaaaggga gaaggtgagc gtttgtttga54840gttgctacaa cattttaaaa cgcgttttgt ttatggtgag actaaagact caaactgtat54900caaagattac tttgtctcag cgtttaactt aaaaacctgc caatatcacc atgagctgtc54960gttaacaaca tacggaggtt acgtatcgag tgaaattcag tttttacacg acattgagaa55020ttttttaaaa cagcttaatt actgctatat tatcacgtct tctcgtgagg cgctaaacac55080attggaaacc gtgacgcggt ttatgacaga tactatagga agcggtctaa taccacccgt55140ggagttgttt gatccggcgc atccatgtgc tatatgtttt gaagaattat gtataacagc55200taaccaaggt gagaccttac atcgtagatt attaggatgt atctgcgatc acgttactaa55260gcaagttcgg gttaacgtgg atgttgacga tattattcgg tgtttaccat atatccctga55320tgtaccggat atcaaacgtc aatccgccgt tgaagcgtta cgaacacttc aaaccaagac55380ggtagtcaat cccatgggag caaagaacga tacgtttgac caaacatacg aaattgcgag55440caccatgctt gattcttata atgtttttaa acctgcccct cggtgtatgt acgccatcag55500cgagcttaaa ttctggttaa cgtctaattc cactgaagga ccccaacgta ctttagacgt55560gtttgttgat aatttggatg tattaaacga acatgaaaaa cacgcagaac ttacagccgt55620aacggttgag ttggcgttat ttggaaaaac tcccatacac tttgataggg cgttttctga55680agaactcgga tctctggatg caattgatag tattttggtt ggcaatcgct catcctcacc55740agacagtcag atagaagcat taattaaagc ctgttatgcc catcatctat cgtcgcctct55800catgcgtcac atttctaacc cgagtcatga taacgaagcc gccttacgcc aacttttaga55860aagagttggg tgtgaggatg atttaaccaa agaggcgagt gacagcgcta cagcatccga55920atgtgatctg aacgatgata gtagcataac ttttgctgtt catggatggg aaaacctgtt55980atccaaagca aaaattgacg ctgcggaaag aaaacgagta tatcttgaac atctgtctaa56040gcgctctcta accagcctcg gtagatgtat ccgcgaacag cgccaagagc tagaaaaaac56100actcagggta aacgtttatg gagaggcctt attgcagaca tttgtttcga tgcaaaatgg56160gtttggggca cgaaacgtgt ttttagctaa ggtttcccag gcagggtgta ttatcgacaa56220tcgcattcag gaagcggcct ttgatgcaca tagatttata aggaatacct tagttcgaca56280tacagtagat gcggctatgt tacctgcact tacacataaa ttttttgagt tggtcaacgg56340cccattgttt aatcacgatg aacaccgttt tgcacaaccc cctaacaccg ccttattttt56400taccgtggaa aacgttggcc tatttccgca cttaaaagag gaattggcaa agtttatggg56460cggtgtcgtt ggttccaact ggcttctcag tccatttagg ggcttttatt gcttttctgg56520ggtagaaggc gttacttttg cacagagact tgcctggaaa tatattaggg agcttgtgtt56580tgcaaccaca ctattcacct ctgttttcca ttgtggggag gtgcggttat gtcgcgttga56640ccgtctaggt aaggatccac gcgggtgcac gtctcaacct aaaggtatag gcagttccca56700cggaccctta gacggcattt atttaacgta cgaagaaaca tgtccccttg tggctattat56760tcaaagtgga gaaacaggga tcgaccagaa taccgtcgta atctacgatt cagacgtttt56820ttctcttcta tacaccctaa tgcagcggct ggctccggat tcaacggacc cggcgttttc56880ataacctccg ttacgggggt gtggttatgc tttttatgca tattttctat gtttgttacg56940gcggttgtgt cggtctctcc aagctcgttt tatgagagtt tacaagtaga gcccacacaa57000tcagaagata taacccggtc tgctcatctg ggcgatggtg atgaaatcag agaagctata57060cacaagtccc aggacgccga aacaaaaccc acgttttacg tctgcccacc gccaacaggc57120tccacaatcg tacgattaga accacctcgg acatgtccgg attatcacct tggtaaaaac57180tttacagagg gtattgctgt tgtttataaa gaaaacattg ccgcgtacaa gtttaaggcg57240acggtatatt acaaagatgt tatcgttagc acggcgtggg ccggaagttc ttatacgcaa57300attactaata gatatgctga tagggtacca attcccgttt cagagatcac ggacaccatt57360gataagtttg gcaagtgttc ttctaaagca acgtacgtac gaaataacca caaagttgaa57420gcctttaatg aggataaaaa tccacaggat atgcctctaa tcgcatcaaa atataattct57480gtgggatcca aagcatggca tactaccaat gacacgtaca tggttgccgg aacccccgga57540acatatagga cgggcacgtc ggtgaattgc atcattgagg aagttgaagc cagatcaata57600
ttcccttatg atagttttgg actttccacg ggagatataa tatacatgtc cccgtttttt 57660ggcctacggg atggtgcata cagagaacat tccaattatg caatggatcg ttttcaccag 57720tttgagggtt atagacaaag ggatcttgac actagagcat tactggaacc tgcagcgcgg 57780aactttttag tcacgcctca tttaacggtt ggttggaact ggaagccaaa acgaacggaa 57840gtttgttcgc ttgtcaagtg gcgtgaggtt gaagacgtag ttcgcgatga gtatgcacac 57900aattttcgct ttacaatgaa aacactttct accacgttta taagtgaaac aaacgagttt 57960aatcttaacc aaatccatct cagtcaatgt gtaaaggagg aagcccgggc tattattaac 58020cggatctata caaccagata caactcatct catgttagaa ccggggatat ccagacctac 58080cttgccagag gggggtttgt tgtggtgttt caacccctgc tgagcaattc cctcgcccgt 58140ctctatctcc aagaattggt ccgtgaaaac actaatcatt caccacaaaa acacccgact 58200cgaaatacca gatcccgacg aagcgtgcca gttgagttgc gtgccaatag aacaataaca 58260accacctcat cggtggaatt tgctatgctc cagtttacat atgaccacat tcaagagcat 58320gttaatgaaa tgttggcacg tatctcctcg tcgtggtgcc agctacaaaa tcgcgaacgc 58380gccctttgga gcggactatt tccaattaac ccaagtgctt tagcgagcac cattttggat 58440caacgtgtta aagctcgtat tctcggcgac gttatctccg tttctaattg tccagaactg 58500ggatcagata cacgcattat acttcaaaac tctatgaggg tatctggtag tactacgcgt 58560tgttatagcc gtcctttaat ttcaatagtt agtttaaatg ggtccgggac ggtggagggc 58620cagcttggaa cagataacga gttaattatg tccagagatc tgttagaacc atgcgtggct 58680aatcacaagc gatattttct atttgggcat cactacgtat attatgagga ttatcgttac 58740gtccgtgaaa tcgcagtcca tgatgtggga atgattagca cttacgtaga tttaaactta 58800acacttctta aagatagaga gtttatgccg ctgcaagtat atacaagaga cgagctgcgg 58860gatacaggat tactagacta cagtgaaatt caacgccgaa atcaaatgca ttcgctgcgt 58920ttttatgaca tagacaaggt tgtgcaatat gatagcggaa cggccattat gcagggcatg 58980gctcagtttt tccagggact tgggaccgcg ggccaggccg ttggacatgt ggttcttggg 59040gccacgggag cgctgctttc caccgtacac ggatttacca cgtttttatc taacccattt 59100ggggcattgg ccgtgggatt attggttttg gcgggactgg tagcggcctt ttttgcgtac 59160cggtacgtgc ttaaacttaa aacaagcccg atgaaggcat tatatccact cacaaccaag 59220gggttaaaac agttaccgga aggaatggat ccctttgccg agaaacccaa cgctactgat 59280accccaatag aagaaattgg cgactcacaa aacactgaac cgtcggtaaa tagcgggttt 59340gatcccgata aatttcgaga agcccaggaa atgattaaat atatgacgtt agtatctgcg 59400gctgagcgcc aagaatctaa agcccgcaaa aaaaataaga ctagcgccct tttaacttca 59460cgtcttaccg gccttgcttt acgaaatcgc cgaggatact cccgtgttcg caccgagaat 59520gtaacggggg tgtaaatagc cagggggttt gttttaattt attaataaaa atgtgtatta 59580cgttactcat gtgtctccat tacgcatcac agggggtatt tatacccgat aatatacaaa 59640acgcgttttg tacctctacc gcacccgata tcttaacggg ggttattatg gaatcgtcta 59700acattaacgc gctacaacaa ccgtcgtcta tcgcacatca tccgtccaaa cagtgcgctt 59760caagtctcaa tgaaacagta aaagattctc cccccgcgat ttatgaagat aggttagaac 59820acacgccggt acaattaccc cgcgacggta caccccgaga cgtatgttct gtgggacagc 59880taacctgtcg agcatgtgca acgaaacctt ttcgccttaa ccgcgacagc caatacgact 59940acttaaacac atgtccaggg ggccgtcata tttcactggc actggagatt ataacgggtc 60000gatgggtttg catcccgcgt gtgtttccgg ataccccaga ggaaaaatgg atggcgccat 60060atattattcc agaccgagaa caaccatcat caggggatga agattctgac accgattaaa 60120tttaacttaa ataaaacctt accacccata aaaacgcctt ctgtttgttt aacacgacac 60180cgcttaacaa aaaaaaaaaa cccaaacacg ccttttatga atgtaatact tttatttgtt 60240ggttaacacc gccccaccat catctgattt gcaaacatat cggcgtcgtc tgccgtggac 60300ccctgtatta aaggggcctt ggaactagcc tccactgcat ttacatcttg tccaactgta 60360tctgtatgtg gggtgcttgt tgtattttgg gatgagcata gacccgaaac gctttgaagc 60420tgttttaata aaatcgatat tcgaggatcc cgtgtcccct ctggtatatt tgtatggtgc 60480gacaaaggca tttgtgtccc attttgtgat tttagctctg taacctcctg ttgcagtttt 60540gccacaaccc cagcaagctc ttcgtgctga ccattagaaa ctctgtgtct cctctgccaa 60600tatgatggag aaactcgacg tctccgatgc gttatatacg ttggttcacc gggaaaatat 60660atatttgagg gaaactctcc gtccatttga gactccccac tagaaaaaga atccaattcc 60720ctttgatcca tgctcttgaa atcccgtttt cctggacgac ggacatcggt tttgtctgga 60780aaatttacac acggggtctg caagtcaata ccccgttcgg cggccaatgc gttcataaat 60840gcggacattt gcatttccaa acgattgggt ggtggatatc ccggaaaccc gtacggtccc 60900ccgaagtgtc ccggagggca accataaccc cctgtattaa atgggaaggc aggcgggtgt 60960ggagatccat atggcccgac gatatactgt ccgttatttg gagctccaat tgatacctgc 61020ggatttttag tctgcccggt taacagctgt gaataatacg cggtaggtat cagtacaaat 61080
tcccctccgg ttggaacgcc cgacgggggc tgtggtgaga taccactagc gttacctgct 61140acagaagcca tatcgctgtc gttcctacac aactgcgtaa cctttaaatg cggaacagtc 61200ttttcacaat cttcatttga ttccccaaca cccaacgcga gatcgtatat gggcccgccg 61260gggtggaatg tggcgtttat aacacccgcg ttgggtaatt tagactccac cccattaacg 61320ttggttatcc gagcaagtcc atatccggtg ctagcctgaa gataaacgtg acccataatt 61380ccggcttcgc gtctacgttt tgcaaccacg tcccatctat ctcttaaaag catattgttc 61440acggctgtgg ataataacac cttggcgagt ttatcttcgc taaccttcca tactttattt 61500aaacccgcgt agtctttaac cagcgacaat aaccgcgctt tactttccat cgataaaacc 61560cggaatggtt caattgaaga ttccggggta cagtcataat tgaccactgt tccaacgcgt 61620cttccaacaa cacataacgc aacatgggta aaaaaattac cgtctggtat ctcattcggg 61680gacaatcgtt ttgaagacag ggatacggag ggtaagtaat ttgtgaccaa gtataacgca 61740cgttctagcg gagataatac agaatctcta tttccaaaaa aattcgaatg ggccgcttca 61800aacagcaccg catgtagttg agggcatcta acgataccca aaaaaaaagg tccgcgtatg 61860tcctcaatga ttgcgattac ttcacccacg acacagtctt ttcgatgatc gatgtttatt 61920ggtattttac tagtaggcgg caaagcggac cgcacaatct ctggggtaat atttaattcc 61980ccttcgtcct ttgaatataa ggctaaatac ccagccacgt ataacgcttc acagttctct 62040tcgtcagctt cagcagccat tataaacacc ccacggaccg gatagtgaat actcacggtg 62100tggaggcaaa ctgaggaatg acacccaaac agacaaaata tagaagatca tagtcactgt 62160taacgttgaa ctgcgcaagg cggcgacttt cttccaatgc cgcccttaca cgcggttggt 62220gcattaacat tccaagtccc cgttcatatt gcaacataac actgtcatgt attgatacca 62280cggcggctat gggtagggat gtaacatttt gtcggcggtg ttctaattcc aatgcaatta 62340agcttatgag ccgatcttgg tactgtccag aagaaatatc tattacggtt cttcctaaac 62400ttccacgact aagctgggta tgcgcgtcta aacaaagagc aactaatcca ggaaacattt 62460cagtcagctc tgtggtccga tttaacgtat acagtggtgc tatatatcgt tcacataaaa 62520attgaaagtt attattaccg cttttaaact tcccatcaaa ccccgtcgct ccgcgcaaga 62580ttacattgtt ggtaggggtt cctgttgctt ctgacacaat caaacccagt tgaaaattat 62640tttttagttt atctccgtat acgttcccgt tccataataa gcgccttaat aataataacg 62700ccgtaatcgt gtcaattgtt aaccttaata gagtttggtc ttccataaga aacacgtttt 62760gggcccgttc taaatacgcc gcggccgcct gttgaatctt gtccacatat gcggtatgat 62820tgcgatcaat aatgtcatta accccaggat taaactgtcc aggtgcaggc ggtaggacct 62880gcaaccgtat aagcgcatcc ataacagaat gtgacgttaa ggcgccttga tcataccgcc 62940ccccacgagc atgaaactgg tcgcgtggta gacgatcata gcaaaattga taactgtttt 63000tattttcgtg tgttgtcata taattcacaa atgtctcagt atattccggt aggtgctcta 63060taaggttccc gaaggacgaa acttgaggtt cgtggacact attagatgtc ctatacatta 63120aatataaaca taataccgca cactcgaacg cggagtacgc tctatctcca acatacattc 63180tcccggcgga ctgtagacat gttaccgttg tgttcataaa cgtacgggaa atgcgcccgt 63240ctttacaatc aactccgcgt gcagctacgg gcctatctaa cacaagccgt tcctgcagag 63300tacgatacca tggcccgaaa acaatccctg gagagttatt gccccttgcc cttcccaagt 63360acaccagggt gataaaatcc acttgaaagt ttgtatcgta ctgcaacggt gcatcatttt 63420tggcaatctg tacctcgggg tgtatagact cattgcgtat tatttctgta cgtgtacatt 63480cctcagattg tgcatctgct tcttccgcct cggcagcagc cgtctccagg gaatccaaaa 63540ccttggccat gcgcgttagt tgttcttcga ggggctttaa acgacgatct atttccgttg 63600gtaacgtaat cgtttccccg cgaaggttgt ctaatgcggc aacggccgcc gcatttttta 63660acgttaacgt atttttttcc aaatcgggat tcatacgccc tcttaactca aacgcgggag 63720ccgtccagta gtgtatgggg aagttggggg ctataaagtt cttagtggta gacaaaaata 63780tcccacattt attcggaaac gagatagatc cgaacccata tctcgccgtc atggtgtctg 63840cagcaaacaa agtcaactgg cgtgaatata aaccggtact gctttaaaag ctgttttctt 63900acccatggga aaacatcccg gttatacttt gtaaaattcc accacaagca cctaaagaag 63960gccttctaag gggtaaatcc accccacaag ctgcattttc ttcaaacttt gttaaagcgg 64020aacgatggca tgatttcgca cgctttttcg caagagagca tacgtgaatt ttctttttgc 64080atagacgtct tcgctctcta acggacctta tcgggggggt atattccgct acattctcca 64140aatgcgacgc tagcataaca aggtttccat gaatcacctt cgggggtaac cgagttacct 64200gtaacaggtt cagaccccgt tgagatacaa acacaaggag gggggtcacc attatttcat 64260cagatcccgt gggtgtggtt tcctttatta aagccacggt atccctcagc tggcgcatac 64320cctcgcaaaa ctggtgatac ttagtagggg tatgtatatt agcgctaaaa cggcaagatt 64380ttaattccac tataaaacaa acggtctttc cggcaccact ggattccgtt tgtataatac 64440aaacacaatc ggggcgtcgg cgtcccaaat ttacttcaaa cgacattgat atgcgtacag 64500ccctttgaac atccacgtgg gataacggcg acaggagttt tgccagcctc gggttgaacg 64560
cgtccgcgaa acctcgacgt acgttatcaa tatccttttt gagtacatcg taaaaacgag 64620tgtggcaacg ttgtcccaaa cgaaaacact tggcccgaat tcgactagcg gacatatttg 64680aagttccgtc ccagaagata acctaagacg cgtttgtcta caataaacat gtcaacggat 64740aaaaccgatg taaaaatggg cgttttgcgt atttatttgg acggggcgta tggaattgga 64800aaaacaaccg ccgccgaaga atttttacac cactttgcaa taacaccaaa ccggatctta 64860ctcattgggg agcccctgtc gtattggcgt aaccttgcag gggaggacgc tatttgcgga 64920atttacggaa cacaaactcg ccgtcttaat ggagacgttt cgcctgaaga cgcacaacgc 64980ctcacggctc attttcagag cctgttctgt tctccgcatg caattatgca tgcgaaaatc 65040tcggcattga tggacacaag tacatcggat ctcgtacaag taaataagga gccgtataaa 65100attatgttat ccgaccgaca cccaatcgcc tcaactatat gttttccctt gtccagatac 65160ttagtgggag atatgtcccc agcggcgctt cctgggttat tgtttacgct tcccgctgaa 65220ccccccggga ccaacttggt agtttgtacc gtttcactcc ccagtcattt atccagagta 65280agcaaacggg ccagaccggg agaaacggtt aatctgccgt ttgttatggt tctgagaaat 65340gtatatataa tgcttattaa tacaattata tttcttaaaa ctaacaactg gcacgcgggc 65400tggaacacac tgtcattttg taatgatgta tttaaacaga aattacaaaa atccgagtgt 65460ataaaactac gcgaagtacc tgggattgaa gacacgttat tcgccgtgct taaacttccg 65520gagctttgcg gagagtttgg aaatattctg ccgttatggg catggggaat ggagaccctt 65580tcaaactgct tacgaagcat gtctccgttc gtattatcgt tagaacagac accccagcat 65640gcggcacaag aactaaaaac tctgctaccc cagatgaccc cggcaaacat gtcctccggt 65700gcatggaata tattgaaaga gcttgttaat gccgttcagg acaacacttc ctaaatatac 65760ctagtattta cgtatgtacc agtaaaaaga tgatacacat tgtcatactc gcgtgtacgt 65620gtttttcttt tttatatatg cgtcatttat taccacatcc tttaatcccg cctttatctc 65880cctaaaacgg agtggtaata ttaaaagccg ccaagcctgt tggtgggtga ggaggggtaa 65940aggcacgctg tgtgcataac gttgcggtga tattgtagcg caagtaacag cgactatgtt 66000tgcgctagtt ttagcggtgg taattcttcc tctttggacc acggctaata aatcttacgt 66060aacaccaacc cctgcgactc gctctatcgg acatatgtct gctcttctac gagaatattc 66120cgaccgtaat atgtctctga aattagaagc cttttatcct actggtttcg atgaagaact 66180cattaaatca cttcactggg gaaatgatag aaaacacgtt ttcttggtta ttgttaaggt 66240taaccctaca acacacgaag gagacgtcgg gctggttata tttccaaaat acttgttatc 66300gccataccat ttcaaagcag aacatcgagc accgtttcct gctggacgtt ttggatttct 66360tagtcaccct gtgacacccg acgtgagctt ctttgacagt tcgtttgcgc cgtatttaac 66420tacgcaacat cttgttgcgt ttactacgtt cccaccaaac ccccttgtat ggcatttgga 66480aagagctgag accgcagcaa ctgcagaaag gccgtttggg gtaagtcttt tacccgctcg 66540cccaacagtc cccaagaata ctattcttga acataaagcg cattttgcta catgggatgc 66600ccttgcccga catacttttt tttctgccga agcaattatc accaactcaa cgttgagaat 66660acacgttccc ctttttgggt cggtatggcc aattcgatac tgggccaccg gttcggtgct 66720tctcacaagc gactcgggtc gtgtggaagt aaatattggt gtaggattta tgagctcgct 66780catttcttta tcctctggac taccgataga attaattgtt gtaccacata cagtaaaact 66840gaacgcggtt acaagcgaca ccacatggtt ccagctaaat ccaccgggtc cggatccggg 66900gccatcttat cgagtttatt tacttggacg tgggttggat atgaattttt caaagcatgc 66960tacggtcgat atatgcgcat atcccgaaga gagtttggat taccgctatc atttatccat 67020ggcccacacg gaggctctgc ggatgacaac gaaggcggat caacatgaca taaacgagga 67080aagctattac catatcgccg caagaatagc cacatcaatt tttgcgttgt cggaaatggg 67140ccgtaccaca gaatattttc tgttagatga gatcgtagat gttcagtatc aattaaaatt 67200ccttaattac attttaatgc ggataggagc aggagctcat cccaacacta tatccggaac 67260ctcggatctg atctttgccg atccatcgca gcttcatgac gaactttcac ttctttttgg 67320tcaggtaaaa cccgcaaatg tcgattattt tatttcatat gatgaagccc gtgatcaact 67380aaagaccgca tacgcgcttt cccgtggtca agaccatgtg aatgcacttt ctctcgccag 67440gcgtgttata atgagcatat acaaggggct gcttgtgaag caaaatttaa atgctacaga 67500gaggcaggct ttattttttg cctcaatgat tttattaaat ttccgcgaag gactagaaaa 67560ttcatctcgg gtattagacg gtcgcacaac tttgctttta atgacatcca tgtgtacggc 67620agctcacgcc acgcaagcag cacttaacat acaagaaggc ctggcatact taaatccttc 67680aaaacacatg tttacaatac caaacgtata cagtccttgt atgggttccc ttcgtacaga 67740cctcacggaa gagattcatg ttatgaatct cctgtcggca ataccaacac gcccaggact 67800taacgaggta ttgcataccc aactagacga atctgaaata ttcgacgcgg catttaaaac 67860catgatgatt tttaccacat ggactgccaa agatttgcat atactccaca cccatgtacc 67920agaagtattt acgtgtcaag atgcagccgc gcgtaacgga gaatatgtgc tcattcttcc 67980agctgtccag ggacacagtt atgtgattac acgaaacaaa cctcaaaggg gtttggtata 68040
ttccctggca gatgtggatg tatataaccc catatccgtt gtttatttaa gcaaggatac 68100ttgcgtgtct gaacatggtg tcatagagac ggtcgcactg ccccatccgg acaatttaaa 68160agaatgtttg tattgcggaa gtgtttttct taggtatcta accacggggg cgattatgga 68220tataattatt attgacagca aagatacaga acgacaacta gccgctatgg gaaactccac 68280aattccaccc ttcaatccag acatgcacgg ggatgactct aaggctgtgt tgttgtttcc 68340aaacggaact gtggtaacgc ttctaggatt cgaacgacga caagccatac gaatgtcggg 68400acaatacctt ggggcctctt taggaggggc gtttctggcg gtagtggggt ttggtattat 68460cggatggatg ttatgtggaa attcccgcct tcgagaatat aataaaatac ctctgacata 68520aaaaacatgt ataataaaaa gtcactataa acgtattctc tacaatactt tattcgcgaa 68580taatacacac tacctttggg tttttttccc gtccccaaat ggtgtttggt gcactctacc 68640aaaaaataga gcgcctaaat atgctatata acgcctccca gcaaaatacg gttcaaaggc 68700attacccgat attgtattgt agtacagggc aatgggaatt gatgatccca ataaacggca 68760tagacgcaca gcgccgttat agcaggggtc tccagagtac agggtatcta agtaccggga 68820tatctcatac tcatgccttt ccgtgacaga aacatcaacc ggaacagtat ccgataaacc 68880aactcctgtt tttgcaaggc gtaaaattcg cacaccttcc ttttttgcaa gatgtgacgt 68940ttccttgtaa cagggaagct gggggagtgg taagaacaac aaagtttcag ccaacgtgcc 69000aataaagccc acttccctca agaggctgtt tgctgtatcc acaatggtcc gtattaaatc 69060ttgagcaact tgatccgtgt catcatcact gggtaacgcg ttaacataac tacgcgttaa 69120atcttcaata acggcataac aattaaacgc ttcccaccga gacagtatat attgaacaat 69180cacgaaccgt tgacaggacg tcagatcacg tccgtaagca tgcccgaaaa atggaagttc 69240cccccgttcg ccatataccg caacaactgc agtatatatc gtctcacggg cttcattaag 69300ttcatcttca agtccaggcc attttctggc tttaaatata acctcgtccg caaaaaaaac 69360cgcacatgat aacgcgcgga tacaatgagt agtggcttta tggcgaggat cccaaatgtc 69420cattacccgg gggatggtcc taatctgtac aaagttactt agtgtaatat gatcggactt 69480cttacgccgt ctaggctgtt tctcagaata cggttcaccc gaaatcggca catcatctgc 69540ttttacgtct tccgtaacca catcagcagc gcgccgacta acaattatac ttgttttttc 69600atcgtcgtta cttccgttaa gcgcgtctcg tatctcgggc gtcccgtcga ataatccact 69660cactagctcc tgcaaacctt ctggtaactc caacatacgc atatacacca atgaaaaact 69720ggcttcgttt ggtacgtaca taaagccatt tgtggtatta atggcggtgg gtgttggaaa 69780caattttagc ttattctcgc gcgtaacatc tacccccgcc accaatgtta aatgcgtcac 69840ggggagggac acgagataat ctgcgagcgt agggtcctcc acttcaacat caaatgttcc 69900gcaaaggtcg cgatccaccg cccccgatcc cgctgcaagt aaggccactc gatccaaaaa 69960cacgcagtta ttattggatg ataccgccca tgtcttcccg gtgcgattga gctcacttcg 70020aacgtaactg gcaacagatc tgtcaccggg tccgaccccg cgaacaacat gtccaaattt 70080tgcgatctcg cctccatgtt tgcggggtat ggaaattaag catcccccgc atataaaata 70140cgccctggta gcacgctcgt taaaataaaa cgttacgccg ttataagata cggttgaatg 70200atatggaaat tccatattaa agcgtttatc ggaacattaa cctcgaactt gccgtcccgt 70260gatcgcgtga tcgccaacct taggtccaca ccgaatatga gaaatatata actacacgca 70320aacattcaaa acaccgtggt atcattaacg tcatatgaaa agatccaatc aatccaatca 70380accacacctc ctaccgttta gcacgtcagc tatgtgacat gctccaaaca tacgtaaaca 70440tttagagagg gtgttataac agtctgtcag gcggggtata ttctacataa tacaaggatc 70500ggctttaact ttgtcaacat ttttactttg gactataaac tgcgactgaa cgttatgaac 70560ccaccccaag cccgcgtctc ggaacagaca aaggacttgc ttagcgttat ggttaaccag 70620caccccgaag aggacgcaaa agtgtgtaaa tccagtgata attcaccgct ttataacacc 70680atggttatgt tatcgtatgg gggtgatacg gacttactat taagctctgc atgtacccgc 70740acatctaccg taaacaggtc ggcgtttacg caacactccg tgttttatat tatatccacg 70800gtgttgattc aaccaatatg ttgtatcttc tttttttttt actataaagc gacacgctgt 70860atgctcttat tcacagccgg gttacttctg acgattctac atcactttcg acttattatt 70920atgttattgt gtgtctacag aaatatacga tcagacctgc tacccttatc tacatcccag 70980caactgctgc ttggaattat tgttgtgact cgaacaatgc tattttgtat tacggcgtat 71040tatactcttt ttatagacac ccgggtgttc tttttgatta ccggacactt gcaaagtgag 71100gttatttttc cagatagcgt ttcaaaaata cttcctgtgt cgtggggtcc aagtccagcc 71160gtgttactgg taatggcggc agttatttac gctatggact gtttggtgga cacggtatcc 71220tttattgggc caagggtgtg ggtccgtgtt atgttaaaaa catctatttc gttttagtcc 71280atttcaataa atgtactata attgttcagt ctaaaaataa tgttgggtat ttataattac 71340cgcccccgtg ttacttggaa acacccatac atatgttcca ctctacatca aacttctcgc 71400agttttcttg ttcccgcaca cgtttacacg tccggattca agtcgcaacg ctgctgacaa 71460aatgacaacg gtttcatgtc ccgctaacgt gattactaca acggaatctg atcgtattgc 71520
tgggttattt aacatcccag cggggatcat tccaactgga aatgtgctgt caaccataga 71580ggtgtgtgca caccgttgca tttttgattt ttttaaacaa atacgatcag atgataacag 71640cctttactcg gctcaattcg atattctttt ggggacatac tgcaatacat taaactttgt 71700gcgttttcta gaacttggac tgtctgtcgc ttgcatctgt actaaatttc cggagctggc 71760ttacgtgcga gatggcgtta ttcaatttga ggtacaacaa cccatgatag cacgtgatgg 71820cccacatccc gtcgatcagc ctgttcataa ttatatggtt aagcggatac acaagcgttc 71880gttaagcgct gcgtttgcaa ttgcatcgga agcgttgagt ttgttaagta acacatatgt 71940cgatgggaca gagattgact catcgttacg tataagagct atccaacaga tggctcgtaa 72000tttacgcacc gttttggact catttgaacg aggcactgcc gatcaacttc ttggtgttct 72060attggagaaa gccccaccgc tatcgctgct ttcaccaatt aataaattcc aacccgaggg 72120acatctaaat cgtgttgcac gcgcggccct actttcggac ctcaaacgta gagtctgtgc 72180ggatatgttt tttatgaccc gacacgccag ggaacctagg ctgatctctg cgtatctgtc 72240ggatatggtt tcgtgcaccc aaccatcggt gatggtatca cgaataactc atacaaacac 72300tcgcggacgg caggttgacg gtgtgttggt aacaacagca accttaaaac ggcaactatt 72360acagggaatt ttacaaattg acgacaccgc cgctgacgta ccagtaacat atggcgaaat 72420ggttctacag gggacaaact tggtaaccgc ccttgtgatg ggaaaggccg tccgcggaat 72480ggatgatgta gcccgccatc tccttgatat aaccgaccct aacacgttaa acataccgtc 72540tataccccca caatccaact ccgattcaac gacagctggg cttccggtta acgcccgtgt 72600tcctgcggat ttagtgattg ttggggataa acttgtattc ttagaagcat tagaacggcg 72660ggtctaccaa gctacgcgcg ttgcctaccc tcttattgga aatatagata ttacgtttat 72720catgccaatg ggagtgtttc aggcaaactc catggacaga tatacacgac acgccggcga 72780tttttcaact gtatccgaac aggatccacg tcaatttcca ccccaaggga ttttttttta 72840taataaagat gggatattaa cacagttgac tcttcgtgat gcaatgggta ccatctgcca 72900cagttcattg cttgatgttg aggccacact tgttgccctc cgccaacaac atttagatcg 72960tcagtgttat tttggtgtat acgtggccga gggtacagag gacacattgg atgttcaaat 73020ggggaggttt atggaaacgt gggcagatat gatgcctcat cacccttatt gggtaaacga 73080acatttaaca attctacagt ttatagctcc gagcaacccg cgtctaaggt ttgaattaaa 73140ccccgccttt gatttttttg ttgcaccggg ggacgtagac cttcccggac cgcagcgtcc 73200cccggaagcc atgccaaccg ttaacgcaac attacggatt atcaacggaa acattcccgt 73260gcctctatgt cccatttcat ttcgagactg tcgcggaacc caactcggtt tgggaagaca 73320tacaatgacc ccggcaacca ttaaagccgt aaaggataca tttgaagacc gcgcataccc 73380aactattttc tacatgctag aggctgttat tcatggaaac gaaagaaact tctgtgcgtt 73440actgcgactg ttaacacagt gtattcgcgg gtattgggag caatcccaca gggtggcatt 73500tgtaaataac tttcacatgt taatgtacat aactacatat ctcggaaacg gtgagcttcc 73560cgaagtctgt attaatatat atcgggattt actgcagcat gtaagagcat tacgccaaac 73620tataaccgat tttacaatac aaggagaggg ccataacggc gagacctcgg aagcgctaaa 73680taacatcctt acggatgaca cgtttattgc acctattcta tgggattgtg atgcgttaat 73740ataccgtgat gaagccgccc gagaccgact ccccgcaatt cgtgtaagcg ggcgaaacgg 73800ataccaagcc cttcactttg tggatatggc cgggcataac ttccaacgac gcgataatgt 73860gttaatccac gggagacccg ttcggggaga cacgggtcag ggtattccca ttaccccaca 73920ccatgaccgt gaatggggta ttctctccaa gatttactac tatattgtca ttcctgcatt 73980ttcccgcggt tcctgttgta caatgggcgt gcgttatgat cgcctatacc ctgcgttaca 74040ggcagttatc gttccggaaa ttcccgctga tgaagaagcc ccaactaccc cagaagatcc 74100aagacaccct cttcacgcac accaactcgt tccgaactct cttaacgttt acttccataa 74160tgcacaccta accgttgatg gtgatgcatt gctcacacta caagagttaa tgggagatat 74220ggctgaacga acgacggcca ttttagtatc aagcgccccc gatgcgggag ccgccacggc 74280aacaaccaga aatatgagaa tatatgacgg agcgctttac catggcctta ttatgatggc 74340atatcaggcg tacgatgaaa ccattgcaac gggtactttt ttttatcccg ttccggtcaa 74400ccctctgttt gcatgtccgg aacatttggc atcattgcgt ggaatgacaa atgctaggcg 74460ggttttggca aaaatggtac caccaatccc tccttttctg ggagccaacc accacgcaac 74520tatacgccaa cccgttgcct accatgtaac gcatagtaag tcggatttta atactcttac 74580atattctctt cttggagggt attttaagtt tacaccaata tctcttacac atcaactacg 74640aacgggattt caccccggga ttgcctttac cgtagtgcgc caggatcgct ttgccacaga 74700gcaactttta tatgccgagc gtgcttctga atcgtacttt gtcggacaaa tccaagtaca 74760ccatcatgat gctattgggg gggtaaactt taccctaacc caacccagag ctcacgtgga 74820cctgggagtc gggtatacag ctgtatgtgc cacagcagcc ctgcgatgcc ctctcacgga 74880tatgggcaat actgcccaaa atcttttttt ttcacgagga ggagtgccaa tgttacatga 74940taacgttacc gaatcgttgc gtcgtataac agcatcgggg ggtcgcttaa atcccaccga 75000
acccctaccc atcttcggcg gactacgtcc tgctacatcg gcaggaattg cacgagggca 75060agcctctgtg tgtgagtttg tggccatgcc ggtgtccact gacctacaat attttagaac 75120tgcatgcaat cctagaggtc gagcatctgg aatgttatat atgggtgacc gtgacgccga 75180catagaggct ataatgtttg atcacacaca atcggatgtt gcttatacag atcgagcaac 75240tcttaaccca tgggcatcac aaaaacattc atacggtgac aggctataca acggaacata 75300caaccttaca ggcgcttctc ctatctacag cccatgcttt aagtttttta caccagcgga 75360ggttaacact aattgtaata cactggatcg gcttctaatg gaggcaaagg ctgtggcgtc 75420gcaaagctcc accgacactg aatatcaatt taaacgccct cccggttcta ccgaaatgac 75480acaggatccg tgtggccttt ttcaagaagc atatccacca ctatgctcaa gcgatgcggc 75540catgttacga acggctcacg cgggagaaac cggggcagat gaagttcact tagcccaata 75600tctgattcga gacgcgtcgc cccttagggg atgtcttcct cttccgcgat aatttcacca 75660cgcccacata cccactccca ataaaagccc tgtagagcgc attggcatct tacttgagat 75720ttggatacgc tcggccgact tggtctgttt cacgcttcct taaacaacat ggctatgcca 75780tttgagatag aggtattgtt accaggagaa ctatccccgg cggaaacatc tgcattacag 75840aaatgtgagg gaaaaattat taccttctca accctgcgtc atcgagcttc actggtggat 75900atagcgctgt cgtcatatta cattaacggt gctccaccag acacgctctc gctgttagag 75960gcataccgaa tgcgattcgc ggcagttata acacgggtca tcccgggaaa gttgttggcg 76020catgccattg gcgtgggtac tcctacaccc ggtttgttta ttcaaaatac atcccccgtt 76080gatctttgta atggcgatta catctgctta cttcctccgg ttttcgggtc cgcagactca 76140attcgcttgg actctgtagg actggaaatt gttttccctt taaccatccc ccagacctta 76200atgcgagaaa tcatcgccaa agtggttgca cgggccgttg agcgcacggc cgcgggtgct 76260caaattttac cccacgaagt tctacgaggc gcggatgtca tttgttacaa tggaaggcgt 76320tatgaactcg aaacaaattt acaacatcgg gacggatcgg atgcggctat tcgcacattg 76380gttttaaatc taatgttttc cataaacgag ggatgtctgc ttttattggc gctgattcca 76440actttgttag tccaaggagc acacgacggt tatgtaaatt tattgataca aacggccaat 76500tgcgttagag aaaccggcca gttaattaat ataccgccaa tgccgcggat tcaagacggc 76560catcgccgat ttcccatata tgaaactatt tcatcttgga tatcaacatc atctagactg 76620ggggatacct tgggaactcg cgcaatttta cgcgtctgtg tgtttgatgg accctctact 76680gttcatccgg gagaccgcac ggccgtgatt caagtgtaaa caggtgttaa taaaaacaca 76740accagtctag ttacatttca cgcgtctggt ttttatttaa taggcataaa cacggaatcc 76800ggtatacatg aactgccaat atacacggac ataattaatg caaccatcag atcatctgac 76860attgttcccg tggtaccttt acccgtgtaa gtttttgtgt ctagattacc cataccgcct 76920ttaattacct ctgtcaggtt atccaactgt ttacatagat actccacggg gtctacacct 76980aactttactg ttagggatac aagctcctgt gaggctatta tatttccgga gttaaatcgt 77040ttaacaaaat agtctacggc cggcgttttt tgtttttgta ataaaaaaaa agggtacgcc 77100acgctacatc cgggaggtat ggaatgataa aacagtaaca ctggagcgga agatagcacg 77160tttccctttt cgaggacagc aaactgttgt gctatagcca acgatatggc aactgcagaa 77220tcctggctgc tgtttccctc tatagaaacg tgtacgtttg taaatgtatt ggggtgtaaa 77280gcgagtatgt ggcctaagca ttgagtaacg caacgcccta tctcactgga agacgtgcca 77340gttaaagctc taagaaaaaa gtgctccaat ccaaatataa tccaatccga cttataacga 77400ccaacaatcg ctacaccagt accagacgct cgtgtatttg aggtaaatgc agggtctacg 77460taaacgtaca acactgacga taatatagca caattcgcaa cggttgacgg ccgatataaa 77520ataaacctct cacgggcagt ttttgtaaat aatggccggt caaaccccac acccccagaa 77580ttctgtttac gcccacctac aatttcctgc acgaaggagt cggccataaa taaatctgca 77640gtgcgccgca tggctccatc cattgtgatg aaaaccggct tatttaatac ataacacgaa 77700caagctgtga catcgctatg tgctaaaaca cgcggcatgt gatcgtcgca tacatatgta 77760acaacgttta acaactgatc cgacgatcca cgtaagttat acaaaaaact tgtacttgct 77820tttccggtat ttgttgatga aacaaaaata attttacaat tggtttgatt taaaaatccg 77880actatagttt gtacagcatc aggtcgaata aaattagctt catccacaaa cagaagatta 77940aaatcttgac ctcggatacc ctggaacgat agaaagatat atagttaccc caccaaagtt 78000taaatgtatc cttaaatacc acgtacgtaa aaaatgtttg aatacgtaca tatttctttt 78060tttttccagt acaaccatat ccggtgtata atggaagccc atttggcaaa tgaaaccaaa 78120catgcacttt ggcataatga tcacacaaaa ggattactac acgttgtgat acctaacgcg 78180gggcttattg cggccggaat agatcccgca ttactgattt taaagaaacc cggacaacgc 78240ttcaaggttg aagtacaaac aagatatcat gctacaggtc aatgcgaacc gtggtgtcaa 78300gttttcgccg cgtacattcc cgataacgcc ttaacaaatc tcttaatacc aaaaacggaa 78360ccatttgttt cacacgtttt ttcggccacg cataattcag ggggattgat tttatcattg 78420cctgtttatc ttagccccgg tttattcttt gatgcattta acgttgtagc gatacgaata 78480
aatactggaa accgcaagca ccgtgatatt tgtattatgt atgcagaact aatcccaaac 78540ggaacgcgtt attttgctga tggacaacgg gtacttttat tatgcaaaca gctgattgcg 78600tatatccgat gcacccctcg tcttgcatcg tctataaaaa tatacgcaga gcatatggtg 78660gcagccatgg gtgaatcaca cacgtcaaat ggggacaata ttggacccgt ttcatccata 78720atcgatcttg atcgacagtt aacttctgga ggtattgatg actcccctgc tgaaacacgc 78780atacaggaaa ataatcggga cgtccttgag ctaataaaac gggccgtaaa cattgttaac 78840tccaggcacc ccgtccgacc ttctagttcc cgcgttgcat ctgggttgct tcaaagtgca 78900aagggccacg gagcgcaaac ttccaacaca gatccgatca ataacggttc ctttgatggc 78960gtccttgagc cgcctggaca agggcgattt acgggaaaga aaaacaattc gtccgccagc 79020atcccacctt tacaagacgt tctattgttt accccagctt cgacagaacc ccaaagtctt 79080atggaatggt tcgacatctg ttatgcccaa ttagttagcg gggacactcc agcagatttc 79140tggaaacggc gtcccctatc aattgtaccg cgacattacg cagaatcccc cagtccgttg 79200attgtagtat cttacaacgg atcctctgcc tggggaggac gtattaccgg aagtccaatt 79260ttatatcact ctgcacaggc tattattgat gctgcgtgta taaatgcccg ggttgacaat 79320ccccaaagcc tacatgtgac agctcgccaa gagctagtcg cgcgtttacc gtttttggct 79380aacgtcctaa ataatcaaac ccccttaccc gcctttaaac caggcgccga aatgttttta 79440aaccaggtat ttaaacaagc gtgtgtgaca tcgctaaccc aaggtcttat aacggagtta 79500caaacgaacc cgactctaca acaactcatg gaatatgata ttgcagattc ttcccaaacg 79560gttattgatg aaattgtagc ccgcacacca gacctgattc agactatagt ttcggtgtta 79620acggaaatgt caatggatgc gttttataac agctccttga tgtatgcggt tttggcgtat 79680ctgtcatctg tatatacacg accacaaggt ggggggtata taccctacct tcacgcttcc 79740ttcccatgct ggttaggtaa tcgttctata tatttatttg actattataa ttcaggaggg 79800gaaatactta agctttccaa ggtccccgtt cccgtagcct tagaaaaggt tggtattggt 79860aattccacac aactgagggg taaatttata cgcagcgcgg atattgttga tattggaatt 79920tgttctaagt atttacccgg tcaatgttac gcgtacattt gtctaggatt taaccagcaa 79980ttacaatcca ttttagtttt accgggggga tttgcggcat gtttttgtat taccgatacc 80040ctacaggcag cactacctgc atcgttaatc ggacctattc tagacagatt ctgcttctct 80100attcccaacc cccataaata aattagtgtc actataaaaa cataacacca gaatctcttc 80160atatttaatt ttacgtcatt tctcccgttt ccaccccctc ttaaaatata aaataaccgg 80220gtgggtggca ttaaacccac aagtacccgg gcggcaatcc gctagactgt ttttctgctc 80280atggaattac aacgcatatt tccgctgtac accgctacgg gtgcagcgcg caaattaacc 80340cccgaggcag ttcagagact ctgcgatgca ttaacgctgg atatgggatt atggaagtcc 80400atcctgaccg atccccgggt gaaaataatg cgatcaactg cttttataac tttaaggatc 80460gctccgttta tcccccttca aacggatact actaatattg ccgttgttgt agccacaatt 80520tacatcacgc gcccacgtca gatgaactta cctccgaaga cttttcatgt aattgtaaat 80580tttaattacg aggtctcgta cgcaatgacg gcgactttaa gaatttatcc ggttgaaaac 80640atagaccatg tttttggagc aacgtttaag aacccgatcg cgtaccccct tccaacatct 80700attccggatc ctcgagcaga tcccaccccc gcagatctta caccaacgcc aaacttaagc 80760gactacttac aacccccgcg gcttccgaaa aatccatacg catgtaaagt tatttctccg 80820ggagtgtggt ggtcagacga acgaaggcgt ttatatgtac tggctatgga acctaattta 80880atagggctat gtcccgccgg atggcatgct cggatacttg gctctgtatt aaatcgactc 80940ctcagccatg cggacggatg tgatgaatgt aatcatagag ttcacgtggg ggcactgtat 81000gcgttacccc atgtcacaaa tcatgcggaa ggttgtgtgt gttgggctcc gtgtatgtgg 81060agaaaggccg gtcagcggga attaaaagtg gaggtagaca ttggcgctac gcaggttctt 81120tttgtagatg tcaccacctg cattcgaatt acgagtacta aaaatcctcg cattaccgca 81180aatcttggcg acgttatagc gggaaccaac gccagtggtc tctctgtacc agtaaattca 81240tctgggtggc agctttatat gtttggagaa acattaagcc gggctattat taacggctgt 81300ggtctgcttc agcgaatttg cttccccgag acacaaagat tatcgggtga accggaacct 81360acaaccacct agtatacctt aactcaaccg ccgttgtgga aaggtatatg tcaacattta 81420cagtaatata ttaaaggtta aatttataaa acactcacgt ttgtgttgtg acttgacgcg 81480aacaccgctg tgctgtaaga cccgtcggta aatgaaaacg taatagattc gccttttaca 81540tgatccacgt aatttgcccc aaaccactgt tccaggcgag acttgatacc ctcaaacacg 81600ggttccgttg ctttgcgtat atgagccgta taacccactt taattcctct aaacgtggcc 81660attactaaag ctattaatgg tacaagaaac catgttttcc catgtctacg tggtaccaaa 81720aacacagttg atttttgttt gaagtgttct aaaacactgt cagaaacact tggcgtgtta 81780aacactgtac gcagaaagca gtcaactctg tcggcatgat cgcccaatag caccgatgaa 81840ataaaatgcg tggtgtgcat gaggatcatt ttttgaaaca gttccaacgt ccccttatat 81900ctgccataga ttggaacgtc aacctttgcg cgtttgccat gacttccaca ctcttcaata 81960
ctctcaaaag atgtttccac aaggtacgaa aaccgttgtg taaaggtaga caactgacag 82020aaactatccg acagagaaaa cgcgcgaaat gtgttcataa caccgctata cgcatttcga 82080tgaggtgctg cttcttccgg tgaatattca taaaactgta cactactgac agcctttttt 82140aattcagggc ttacgtttgc atttaccgaa tatcgccatg gtttcaaaac tacattgggg 82200gtacagttgt accctgttga cgatagaaac gcgccaaaca ttgcccgtcg agcagtagcc 82260gagaacagtg gaatatattc acaacagttg tgaagcgttc caattccggg aataacggcc 82320tgatgacgtc gggttacatc tatagcaaaa ttcagaaacg ggatttgggt tgcgtttccc 82380agagaccctt gccgcgtgga acacggggta ggggactcca acgtcccaaa gcgttcatcc 82440ctacgacgct ttagacgttc aaaatatctt acagattctt caccaagcgt acgaccaaac 82500attatcaatg acatttaaca tcaattcacg gaatccgcct catctcttgt aagcagtaaa 82560acaggaagcc gcgtcatctt acgtactcgt tacgtatata tcataaacat tttcagggcc 82620gcattcattc actttggtca tgtcaggcca cactccaacc tacgcttctc ataggcgtaa 82680ccgtgtcaaa ctagttgagg cgcataaccg cgcggggtta tttaaagaac ggaccctcga 82740tctaatccgt gggggtgcga gtgtacaaga tccagcattt gtgtatgcct ttactgctgc 82800aaaagaggcc tgcgccgatt taaataacca gctccgctct gcagctcgca tagcttcagt 82860tgaacagaag attcgtgata tacaatccaa ggttgaggaa caaacaagta ttcaacagat 82920tttaaataca aacagacgct atatagcacc cgattttatt cgcggtttgg ataaaacaga 82980agacgataat accgataata tagacagact ggaagacgcg gtaggaccga acatcgaaca 83040cgaaaatcat acttggtttg gagaagacga cgaagcgtta cttacacaat ggatgctgac 83100gacacacccc ccaacctcca aatatctcca actgcaggac ctttgcgttc ccaccacaat 83160accgacggac atgaaccaaa tgcaaccgca gccgatcagc aagaacgaga atccaccaac 83220cccacacacg gatgtgtaaa tcatccatgg gccaatccgt caactgcaac atgcatggaa 83280tcaccagaac gatcacaaca gacaagctta tttttattaa agcacggctt aacgagagat 83340ccaatacatc aacgcgaaag ggtggacgtt tttccacaat ttaacaaacc cccatgggtt 83400tttagaattt ccaaattatc ccgtttaatt gtacccatct tcacgctcaa tgaacagtta 83460tgtttttcta aattacagat tcgagataga cccaggtttg cgggacgggg aacgtatggg 83520cgtgttcata tatacccatc gtcaaaaata gctgtaaaaa ccatggacag tcgtgttttt 83580aatagagagt taattaacgc gattttagcg agtgagggtt ctatacgagc aggggaaagg 83640ctaggtattt ctagcatagt ttgcctttta ggtttttcgt tacaaaccaa acagctactg 83700tttccggcat acgacatgga tatggatgaa tacattgttc gcctgtccag acggttgaca 83760atacctgatc acatagacag aaaaattgcc catgtatttt tagatttggc tcaagcgttg 83820acgtttttaa atcgaacgtg cggcctgacc cacctagatg tgaaatgtgg caatattttt 83880cttaacgtcg acaactttgc ctcgttggaa ataaccacag cagtaatcgg agactatagc 83940ctagtaacat taaatacgta ttccctttgt actcgagcga tatttgaagt tggaaatcca 84000tcccacccgg agcacgtact acgcgtaccc cgggatgcat cgcagatgtc atttcgtttg 84060gtgttgagtc atggaacaaa ccaaccccct gaaatcttgc ttgattatat taatggaacg 84120ggccttacta aatatactgg aaccttgccc caaagagttg gacttgcgat tgatctttat 84180gcattgggcc aagcactctt agaagttatc ctgctaggac gtcttcccgg acaactgccc 84240atttcagtac atcggacccc gcattatcac tactacggtc ataagttatc accagatttg 84300gcgcttgata cgctggcata tcgatgtgtc ctggcgccat atatactccc atctgacatc 84360cccggggact taaattataa tccctttata cacgccggag agctgaacac ccgtatttcc 84420cggaattctt tacgccggat attccagtgt cacgcagtgc gttacggcgt aacgcactca 84480aagcttttcg aaggcatacg cattccggcc tcattatacc cagccactgt tgttacgtcg 84540ttgttgtgtc acgataattc agaaatacgc tcggatcacc ctttattatg gcacgatcgg 84600gattggatag gatcgacata agcccccagc cagccaaaaa aattgcccgt gtgggaggtc 84660tacagcaccc ttttgtaaaa acggatatta acacgattaa cgttgaacac cattttatag 84720acacgctaca gaagacatca ccgaacatgg actgtcgcgg gatgacagcg ggtattttta 84780ttcgtttatc ccacatgtat aaaattctaa caactctgga gtctccaaat gatgtaacct 84840acacaacacc cggttctacc aacgcactgt tctttaagac gtccacacag cctcaggagc 84900cgcatccgga agagttagca tccaaattaa cccaagacga cattaaacgt attctattaa 84960caatagaatc ggagactcgt ggtcagggcg acaatgccat ttggacacta ctcagacgaa 85020atttaatcac cgcatcaact cttaaatgga gtgtatctgg acccgtcatt ccacctcagt 85080ggttttacca ccataacact acagacacat acggtgatgc ggcggcaatg gcgtttggaa 85140aaaccaacga accggcggca cgagcgatag ttgaagcatt gtttatagat ccggctgata 85200tccgtactcc tgatcattta acgccagaag ctacaactaa gttttttaat tttgacatgc 85260tcaataccaa atctccaagt ctccttgtgg gtacaccaag aatcggaacg tatgaatgtg 85320gacttttaat cgacgttcga acgggactta taggcgcgtc gttggacgtt cttgtatgtg 85380acagggaccc tttaactggc accctaaatc cccaccctgc agaaaccgac atttcatttt 85440
ttgaaattaa atgtcgtgct aaatacctct ttgatccaga tgataaaaat aacccgctcg 85500gtcggacgta caccacgtta ataaatagac ctacaatggc aaatctacgg gactttttat 85560atactataaa aaacccatgt gtaagcttct ttggaccctc agcaaaccca agtacacgcg 85620aggccttaat aacggatcac gttgaatgga aacgtttagg atttaaaggt gggagggccc 85680ttacagaact cgacgcccat catttgggcc tcaatcggac aatctcatcc cgagtgtggg 85740tatttaatga tccggacata caaaagggga caattacaac cattgcatgg gccactggag 85800atacggctct tcaaattcct gtatttgcca atccgcggca cgctaacttt aaacaaattg 85860ccgtacaaac ctatgtatta tccggttact ttccagcgct aaaactacgg cccttccttg 85920tcacctttat aggacgtgtg cgccgaccac acgaggtggg agtcccattg cgcgtcgata 85980cacaagcggc tgccatttac gaatataact ggccgactat cccaccccac tgtgcggttc 86040cggttatagc cgttctaacg cctatcgaag ttgatgtgcc tagagtgaca aaaatactta 86100aagacacagg aaacaacgcg attacatcag cattgcggtc attgcgatgg gacaatcttc 86160atccagcggt cgaggaggaa tctgtggatt gtgcaaacgg tacaacgagc ttgttacgtg 86220caacggagaa accgttgctt tgaactcaga gttctttgaa gactttgact ttgatgagaa 86280tgtaacagag gacgccgata aatccacaca acgccgccca cgagtgatcg atgtaacacc 86340aaaacgaaaa ccttcgggaa agagctccca ttccaaatgc gcaaaatgtt aaaccctgat 86400aaacgttcta ataaaaacat caaatcatgg ttggttactg tgaatgtttg ttttattgct 86460tgggggttta caagtacaac ccacgctact cccacccact gtttgatcgc tcgtataaca 86520gctcatcctc gcggtccgtt tcatatgttg agtcattttc atagacgtag ccgtagcctt 86580gtgatgggta atttgtgcgg cgagaatttc tatgtgcagg ttttactttt cgtatgtatc 86640cccgtacccg ctcgggtact cttcttacgg caccgtagaa ccgactgcgt ttctgtcgat 86700gatacacata tgcacgcatc aatctgagaa gcaacatgac aacggaaaac acggccaggc 86760aagccaaggt tccccgagtt gtgggaatta accgtggaga ttgaaccgat atagggtcat 86820ataatcggtc catatacgag tgcgcggcgg ttcccaacgt agcacaggcc acgagcgttc 86880ccagggacgg tcctattaac acgtgtatat aatgcgccaa aattaattct gatactataa 86940gatatacaac tgacaatgta ctaaatgtag acatggccac ggacaccgat gaccacagtc 87000ccgtatgtag atgattcgcc accacaagtt ccagcattaa tgatacaaat aggatacata 87060tcgccatcaa cgcagccatc aaattcacga acactgcgcg cgtaggcccc gcaaggcgat 87120ataaaaagac gctctgctgt cgtaaatttg cgaccgcttt tatgttcgtt tcgtccaatt 87180ttccgcgtcc acaaaaatac gttgtaaata ttacacttgt cgcaaaatgt ccaagatata 87240atgtagcagc cacgccgatt tgcttgtaag ctaataataa cacaacggcg tttaataacc 87300acaatgacaa aagaccccaa aaaagtgttg tgggatctac aactaaccat gcaacaccgg 87360agctttgccg gacacgttga tttttcgttt ctcggtgtat aatcgcggcc gtgatcagtg 87420tatataccgc catggccatt gccgttaaag ccgtgtagta agtaaatgcc acaacgctat 87480gtggttccaa aaacaaaacc ggggcgctgt atccacctct atttccggac catacccccc 87540catctagggt ggcgttaaat aactcataat caactacggc agcataaaaa caagggatcc 87600cggtatattc agaagaggcg gcaattaacg tagccaggag cattaccgca cccaaagtga 87660acatcatcac ctgaattatc caaattcgcc aattaagcgt atccatttga tgatctaacg 87720cttccacctc gggtgtcgtg gtgtcgtacg gtgagacttt ttcagaacgc ggccccttct 87780tttgagttcc catgtctccc aacaccgggg agagcaacgc cgccgtctat gcgtccagta 87840cacagctcgc gcgggcgtta tatggagggg atctggtttc gtggattaaa cacacccacc 87900cgggaattag cctggaactg caattggatg ttccagtaaa actaataaaa cctggtatgt 87960cacaaactcg cccggtaacc gtcgtacgtg cccctatggg ctctggtaaa acaacagcct 88020tgcttgagtg gcttcaacac gcgttaaagg cagatattag cgtactggtt gtctcatgtc 88080gccgtagctt tacccagacg ttgattcaac ggtttaacga tgcaggcctc tccggattcg 88140taacatattt gacatccgag acatatatta tgggttttaa acgtttgatt gtgcaacttg 88200aaagcctaca ccgcgtatcc agcgaagcta tcgacagcta cgacgtatta atactggatg 88260aggtaatgtc agtgattgga caattatact cccccacaat gagacgtctt tccgcggttg 88320atagcctatt atatcgtctt ttaaatcgct gttctcaaat tatcgcgatg gatgctacag 88380taaactctca gtttattgat ttaatctccg gattgcgtgg agatgaaaac atacacacaa 88440ttgtgtgtac atacgcggga gttgggttct ccggaagaac ttgcacgatc ctgcgtgata 88500tgggcatcga cacgcttgtg cgagtcatta aacgatctcc tgaacacgag gatgtacgta 88560ccatacacca actacgtgga acattttttg acgaactagc actacgatta caatgtgggc 88620ataacatctg tatattttca tcaactttat cgttttcgga gctagttgct cagttttgtg 66680caatatttac agactctatt cttattttaa actcaactcg gcccctatgt aatgtaaacg 88740aatggaaaca ttttcgcgtg ttggtgtaca ctaccgttgt gaccgttgga ttgagttttg 88800acatggctca ttttcatagc atgtttgctt acataaagcc aatgtcatat gggccggata 88860tggtatcggt ctaccagtca ttagggcgtg tacgtttatt gctacttaat gaagttttga 88920
tgtacgtcga tggctcaagg accagatgcg gacccctgtt ctcgccaatg ttactaaact 88980ttaccatcgc aaataaattt caatggtttc ctacacacac ccaaataact aacaaactgt 89040gctgtgcatt taggcaacga tgtgcaaatg catttacacg ctcgaacacc catctcttct 89100caagatttaa atacaaacac cttttcgaga gatgctctct ttggagttta gccgatagca 89160ttaatatctt acaaactctt ttggcctcta accaaatttt ggttgtattg gatggcatgg 89220gtccaataac ggacgtttcc ccagttcaat tttgtgcatt tatacacgat ctcagacata 89280gcgctaacgc cgtagcttcc tgtatgcgtt ctcttagaca ggacaatgac agctgcttga 89340ccgattttgg cccttccgga tttatggccg ataacattac cgcgtttatg gaaaagtatc 89400ttatggagtc aattaatacc gaagaacaaa ttaaagtatt taaagccctt gcatgtccaa 89460tagaacagcc tagactagtc aatacggcaa tattgggggc gtgtatacga atacctgaag 89520cgttggaagc atttgacgta tttcaaaaaa tatacacgca ctacgcttcc ggttggtttc 89580ccgtcctgga caaaaccggg gaatttagca tcgcgactat aactaccgcc ccaaatttaa 89640ccacacattg ggagctgttt cgccgttgtg cctatattgc aaaaacactc aagtggaatc 89700cgtccaccga aggctgtgta acacaagttt tggatacgga cattaataca cttttcaatc 89760aacacgggga ttcgctggct caactaatat ttgaggttat gcgctgtaac gttaccgacg 89820ctaagattat attaaaccgc ccggtttggc gaacaaccgg attcttagat ggatgccata 89880atcaatgctt ccgtccaatc cctacaaaac acgaatataa cattgctcta tttcgtttaa 89940tttgggaaca attatttggc gcccgcgtaa ctaaaagtac ccagaccttt ccgggaagta 90000ctcgtgtgaa aaacctaaaa aaaaaagatc tagaaacttt acttgattca attaacgtgg 90060atcgttctgc atgtcgtacc taccgccagt tgtataacct gcttatgagc catcgccatt 90120cgttctccca acagcgttac aaaattactg cccccgcttg ggcacgccac gtgtattttc 90180aagcacatca aatgcacttg gccccgcatg ccgaagccat gctacaatta gcgctatcgg 90240aactgtcccc gggatcgtgg ccgcggataa acggggcggt aaattttgaa agtttataac 90300ccattaatac catatatgga catccatagg gggggttaca taaatactaa gcctctgtac 90360aacacaaagg gcctctaaca atgcactgaa ccacaaccaa gctatggacg caacgcagat 90420taccttggtt agagaaagcg gacacatttg tgccgcaagc atatacacat cctggacaca 90480gtccggacaa ttaacacaga acggtctttc cgtgttatac tacttattat gcaaaaactc 90540atgtgggaaa tacgtcccta agtttgccga aattaccgta caacaagagg atttatgtcg 90600ctactccagg catgggggga gtgtttctgc ggcaacgttt gcgtctatct gcagggcggc 90660gtcctcggct gcgttagacg cctggcccct tgaaccactg ggtaacacag acacctggcg 90720ttgtctccat ggcactgccc tggccacttt acggcgcgta ttagggttta aatcgtttta 90780ttcgccagta acattcgaga ctgatacgaa tacaggtctt ctgttaaaaa caatccccga 90840tgaacacgcg ttgaataatg acaacacgcc atctaccgga gtattgaggg ctaattttcc 90900cgtggccatt gatgtttcag cagtcagcgc atgtaacgcc cacacgcaag gtacgtcgct 90960agcctacgcc cgcctgaccg cacttaaatc taacggtgac acccagcaac aaacaccttt 91020agacgtggag gtaattacac caaaggccta catacgtcgg aaatataagt ctacgttttc 91080cccccctata gagcgggaag gccaaacctc cgatttgttt aaccttgaag aacgccgctt 91140ggttcttagt ggcaatcgcg caattgtggt aagggtactc ttaccgtgtt attttgactg 91200tttaacaacg gattccaccg ttacatcttc cctttcaata ttagcaacat atagactgtg 91260gtacgcggcg gcgtttggaa aacccggggt tgtccgtcca atctttgcgt atttaggccc 91320ggaactcaat ccgaagggtg aagacagaga ctacttttgt actgtcggat ttcccggatg 91380gaccactctt cggacacaaa ctccagccgt cgaatctatt cgcacggcta cggagatgta 91440catggaaacg gatgggttgt ggccagtaac cggtattcag gcctttcatt atctagcccc 91500ctggggacag catcccccct tacctccgcg ggtgcaggat cttattgggc aaatccctca 91560agatactgga catgcagatg caactgtcaa ttgggacgcg ggccggatat ctaccgtctt 91620caaacagcct gtacaactac aagatcgttg gatggcaaag tttgatttca gcgccttttt 91680tcccacgata tactgcgcta tgttccccat gcattttaga ttaggcaaaa tcgtcctggc 91740tagaatgcgt cgaggaatgg ggtgcctaaa acccgcgttg gtgtcttttt ttggggggtt 91800acggcacata ctcccgagta tatacaaagc tattattttt atagccaatg aaattagcct 91860ttgcgtcgaa caaacggcct tggaacaggg ctttgctata tgtacttata taaaagatgg 91920attttgggga atcttcgccg atttacatac gcgcaatgta tgttcagatc aggcacgttg 91980ttcggcctta aatttagcgg ccgcctgcga aagagcagtc acgggcttat tacgaattca 92040actaggtctt aactttacac ccgccatgga accggtactc cgggtcgagg gtgtgtacac 92100tcacgcattt acctggtgta ccacgggaag ctggctgtgg aatttacaaa caaacacgcc 92160tccggattta gttggcgtgc catggcgaag tcaggcggcg cgagatttaa aggagcgtct 92220ttcaggactc ctatgtaccg caacaaaaat tcgagaacgg atacaggaaa attgcatatg 92280ggaccgtgtc ctatacgaca tatgggccgg acaagttgtg gaggctgcca gaaaaacata 92340cgtcgatttt tttgaacatg tttttgatcg ccgttatact ccggtatact ggagtcttca 92400
ggagcaaaat tcggaaacaa aagcaatacc ggcatcttat ctgacatacg gacacatgca 92460agataaggat tataaaccaa gacagataat tatggttcgt aatcccaacc cacatggacc 92520tcctactgtt gtttactggg aattgctacc atcgtgtgcc tgtattcccc ccatagactg 92580cgctgctcat ctcaagcccc ttatacacac gtttgtcact attattaacc atcttctaga 92640tgctcataat gatttttcaa gtccatcatt gaaatttact gacgatcccc ttgcttcata 92700taacttcttg tttttatgac aaaaaaacac gccgcaacaa cccatcctta aaataaaagg 92760tttatttact ttacaacccg tggtgaattt ttatacgttt caaataactg aacatttttc 92820ggtgttacca tggtgcgatt taaccaccaa aaatatacgc tcttctgata ttccgaatct 92880cgtaaaggtc catttaacaa tcccgggggc acttgcacca caccatctgg acaggggggg 92940gttccgtggg gcaggtcaaa acgctgaccc accccacatg aatatatagc ctttataata 93000ttgggggccg ttccaggctg agggttcagt aacttaacaa acatataatg cggcaatacg 93060cgggtttttg taaaggggtt gttatcaacg acatacatta gagtgtttaa caaccataaa 93120actccctcat ataaaaaccg acgcattttt tccaaaggtc ctatttgaca ctcaacgcgt 93180ctaagatata cagacaattg tacaaacagc gatggagatg ccccggaggg cccaatgcct 93240tccagataca ttaaaataac acataaggta aaatctagga cattatccgg gcggaataga 93300gtcatccgat agattaacag gcgcggaggc acccccaccg tatacaccct atcttcaacc 93360gcagttaata cggaaaaaat aaatccgcgg aacgctggtt gagtaacaca ctccatgtag 93420taacgatcac aggacacctc acttgaatca ccattcaaca ctactaaaac ggtctcttgg 93480tgttccggtt ttacgcgcag tgatacaaca gagtttgcca aaaagcgtgg cttcaaaccg 93540gttacctccc gcgcctcgca tacgaatctt ggtattgctt gtattctaag atcttcgatc 93600acgtcgctca catccaaccc ctcttcggct cgtgttagta agttgtcgat cgttacgctg 93660caacctaaaa tgctgggtat atttattccg gacatcccat cggccatccc cgcgcctccg 93720gtttgctcga attttatcca gtaaggtcga atccgctgca tttaccttgt gtacccgtaa 93780cctctcaggg gggtgtcctt tcataaaatg ggataggttt ttatatccaa catgcatgta 93840ttggttattt attttattgg gttccgggat tctttcgtca tcttctgtag ggtcaggcaa 93900accccaggaa ggacttggtg ttctccgtgg gccccgtttt attacctctg cgcgaacctg 93960catttcatat aatattcgga tttgggataa ataggactct gttctcgcct ttttaaaaat 94020agcctggcat aactcttcct ctgacctatg tacctcgctt tgagttacca agaatcctaa 94080tcgggtggcc cgtaatatga atgaaaaata cggcgcaact agtaatgaga ttgacgcatt 94140tgaatatgat acagaaattt cctggccttg attattgttt acccggtgaa gcttaaaaca 94200gcgaacaagt tcctgtttcc atagctcaga caaacgtttt atatcatctc cataaggggg 94260gatataacga gattgaaaac tattggcaat atatgcatca tcccctatta tgccggtaag 94320atctataacc tcgtgattta aatcggcaat acgtgtttct tctgccattg taatatgtga 94380ccctttagat ggctttattt ttaccctctc ttcccgtaac cgtttcagct ctccttcttt 94440gaactggagc ctttcggtca gatcgctgtt cacatccttg agaccctcaa tggttttgaa 94500taaattattc acataaccct cgagcatgcc gttgatactg ttgaccaccg atgttttaaa 94560cgcactttga acgtttgttg ttccggacat tgcccccccg ttaaaggatt ggttggcctt 94620gccaaacccc ggttgtgatg tgtccaccga tccacttcct tccagaatgt gattgcccgt 94680ttcttctaga taggaacgta cggtttcggt aatatctcca acatgtctca tgttttttaa 94740gttaactatt agctttacaa gtctagacgc ggccgatcca gcccgtgttg tatcgttctc 94800gcccattata cgatcaaccg cacgtgtgct gtgagatcta tcatcttcat tccggcgacc 94860tattaacacg cgcaaagggg ctgtatttaa aacttggcag acgcgagcat gttcacgtaa 94920tgcataacag gccaacacct ccccagaaag ccgctgtaag ggtgagtcaa atactacacc 94980ctccccacat acaacgggcg gccacacgac caaacactct cccttcatgc ccgttacatc 95040atcctttgcc ataattaatc ttcggttata attataataa agacgcgtcc tatcataatc 95100cataatagca acattttgca tacactcaac taggcttgtg acaaccgccg cccctctggc 95160caacgttgca tcggcaactt ttaacatctg ggacagttct gccgcttgac ccatatacgt 95220atttaatggt gcaggggttc cattctgttc tgatcgtacc tttcttacaa cgggcacaat 95280acctacacag gctatccagt ccacgtattt ggcaaaaccg acccttccat ttaaaccact 95340ggtatagaga caaccggtta ttccacgcag aaactcaagt aacgatgact gtaatgtttg 95400acgccaggtt tcaaaaacct gatgtgcaag ccgtacggct tctgattctc cacataaccc 95460ataacgttcc gctagagccc cggcatgcag gttacattgt tggatgtggt ggtcccaatc 95520tgctgctagg tcctcatacc gagttgcatc caacgcgttc atcaaaacgg ttgcctgaac 95580ttggcgaatt acagtttccg tagaccgtac agcgctatat atgcottgtc catcggtata 95640tccaaagtca ccggctagga tttttcgaaa caacatactt tgcgtggttg ggtgtattaa 95700catccagcca tcttcctccg gaaatgtaca aaaccctata tccggggcgt actcattcca 95760gtatatatcg aacatgttct tgtattggtc atttgggtta cttccattca agccctggtc 95820aatagaaaca gaacttgcta tccttttttc ttcactaccg gaactgttat taaaaagaga 95880
cgttatttcg gccattgaaa accacgatga aaagatcaat ttctgtagac agttcttcac 95940ccaaaaacgt ttttaatcca gagacgccca atggatttga tgacagtgta tatttaaact 96000tcacctctat gcatagcatt caacctatcc tctcacggat tcgagaactt gccgcaatta 96060cgattccaaa agaacgtgtt ccgcggttgt gttggtttaa acagttactc gaactgcaag 96120cgcctcctga aatgcagagg aatgagctcc ccttctccgt ttatttaatt agcggaaatg 96180ccggctccgg aaaaagcacg tgtatccaaa cgcttaacga agctatcgat tgcattatta 96240ccggatccac cagggttgct gcccaaaatg ttcatgctaa gttatcaacg gcttatgcga 96300gtcgtccgat aaacacaatc tttcatgaat ttggttttcg cggaaatcac attcaggctc 96360agctgggccg ttacgcatat aactggacta cgaccccccc ttctattgag gacctgcaaa 96420aaagagatat tgtatactac tgggaagttt taattgatat aacaaaacga gtgtttcaaa 96480tgggggacga cggtcgcgga ggaacatcga catttaaaac cctgtgggca attgaacgtt 96540tgcttaataa acctacaggc tcaatgtccg gaaccgcgtt tatcgcatgc ggttcccttc 96600cggcttttac ccggagcaac gttattgtta ttgatgaagc aggattgcta gggcgtcata 96660ttctcacggc cgttgtttac tgttggtggc ttttgaatgc tatatatcaa agccctcagt 96720acataaacgg tcgaaaaccg gtcatagtat gcgtcggttc gcccacccaa actgactcgt 96780tagaatctca ttttcaacat gacatgcagc gttcacacgt aactcctagt gaaaatatac 96840tcacgtatat aatctgcaat caaactctgc gtcaatatac taacatctca cataactggg 96900caatctttat taataacaaa cgatgtcaag aggacgattt tggaaatctt ttaaaaacgc 96960ttgagtacgg gctacctatt accgaagcac atgcgcgtct ggtcgataca tttgttgtac 97020ctgcatccta tattaacaat cctgctaatc tccccggatg gacgcgtctg tattcgtcgc 97080ataaggaggt gagcgcgtat atgagtaagt tacacgcgca tttaaaacta tcgaaaaatg 97140accatttttc tgtgtttgcc ttaccgactt atacattcat ccggctaacg gcatttgatg 97200aataccgcaa attaacggga caacccggac tttctgttga acattggata cgggcaaact 97260ccggtcgttt gcacaattat tcccaaagcc gagatcatga catgggaaca gttaaatacg 97320aaacacattc aaatcgcgac ttaattgtag cccgtacaga catcacttac gtgctaaata 97380gtctcgtagt tgtaaccaca agactacgta agttagttat tggattcagt ggtacatttc 97440aatcgtttgc aaaggtttta cgtgacgact cctttgtgaa ggctcgagga gagacatcca 97500ttgaatatgc ttaccggttt ctgtcaaacc taatctttgg aggcttgatt aacttttaca 97560attttttgtt aaataaaaac ctacatcccg ataaggtatc gttagcatac aaacggttag 97620ctgccttaac cctggagtta ttgtctggaa caaacaaagc ccccttacac gaagcagcgg 97680ttaatggggc gggtgccggg attgactgtg atggtgcagc tacttctgcc gataaagcct 97740tctgctttac caaagccccc gagtccaaag taacggcctc catacccgaa gacccggatg 97800atgtaatttt tacggcactt aacgacgagg ttattgactt ggtatactgc cagtacgaat 97860tttcctatcc caaatcatcc aatgaggtcc atgctcagtt tctgttaatg aaagctattt 97920acgatggtcg atatgccata ttagcagagc ttttcgaaag cagctttaca accgccccct 97980ttagcgcgta tgtcgataat gttaatttca acggaagcga gcttttgatc ggcaatgtgc 98040ggggggggct gttatctttg gcattacaaa cagatacgta tacccttttg gggtatactt 98100ttgcacccgt gccagtcttt gtagaggaac tgacccgaaa aaagctgtac cgcgaaacta 98160ccgaaatgtt atatgctcta cacgtacctc ttatggtctt acaggatcaa catgggtttg 98220tgtccatcgt aaacgctaac gtatgtgaat ttaccgagtc tatagaggat gcagaattgg 98280caatggccac cacggtggac tatggcctta gttctaaact agccatgaca attgcacgct 98340cacagggcct gagtttagag aaggtagcta tctgttttac ggcggataaa ctgcgcctaa 98400atagtgtgta tgttgccatg tcgcgtacgg tctcctctag gttcttaaaa atgaatctaa 98460accctctacg ggaacgatat gaaaaatccg cagaaattag cgatcacatt cttgccgctc 98520tacgtgatcc caacgtacac gttgtgtatt aaagcattgt ataaaaacac gcatgcgggc 98580ttgctgttct catttctagg ttttgtctta aatacacccg ccatgagcat ctctggaccc 98640ccaacgacgt ttattttata taggttacat ggggtcaggc gggttcttca ctggacttta 98700ccggatcatg aacaaaccct ctacgcattt acgggtgggt caagatcaat ggcggtgaag 98760acggacgctc gatgtgatac aatgagcggt ggtatgatcg tccttcaaca cacccataca 98820gtgaccctgc taaccataga ctgttctact gacttttcat catacgcatt tacgcaccgg 98880gatttccact tacaggacaa accccacgca acatttgcga tgccgtttat gtcctgggtc 98940ggttctgacc caacatctca gctgtacagt aatgtggggg gggtactatc cgtaataacg 99000gaagatgacc tatccatgtg tatctcaatt gttatatacg gtttacgggt aaacagacct 99060gacgatcaga ccacaccaac accaaccccg caccagtata catcgcaaag gcggcagcct 99120gaaaccaact gtccttcacc acaaccggcc tttttcacat cagacgacga cgttctttcg 99180ttaatattac gggacgccgc aaacgcgtaa agacagattc aagactaaca tttatcccaa 99240ctgattacat ttcatacgcg aataaacgac acaaaaaatt tatatttaac ggcttttaat 99300ttgaagacac ctatcctctt aacgttgagg agccttgcag gttgggtgcc gcgcttcacc 99360
ggtattatac ataaccgatt taccgtgttt acggcagtct gaccatttac cagtgtatgt 99420ctgtaatacg acgttgttgt gtcccgacaa aattaactcg cgtacaaatt tctgatgttc 99480ccccggcgtg gcaacgctgg catttccaaa cacattacgt tctcgtacgt ccatgaccgc 99540tattttcagt attaattggt tggtcggtca aagtattttc cttatgtaaa aggacacgat 99600ctaaagccgt aaactcgtac acaaacactg gtaccaacgg acgcgatttt ccgtccgttg 99660agcgggtgta atatcggcga ggtcttcttg cacgaatact ctcgtacagt aggtttctga 99720cacggggtgc atgggttttt tgacacaaca caaacatttg caggctctta tgactggatg 99780gattgaattt atttttagat agggtcacgt gtttttgtcg tgacacgcct cgaccagaaa 99840aggctgcggt tttcgtacac gcgaccgtta tttcacaggc gttcataatc aagctgcggc 99900ggatggtgtc ggttaattgt ctccgcccaa gttcgtcaat agatgatacc atgaacaacg 99960tatcaaatgg tacatagtcg tctttggttt tctcaataca gcccgcgtgc ccaatcggaa 100020aattttcatt tgcatcaacg ctattttctg taaaatcggt ctgaacactg tgttggctgg 100080ctacctgttt aaaatttggg atcgaacacg gtccacgatg caatccccaa ccccattgaa 100140gcaatgccgt cggtacggaa ggaggcaact ccgaaaacat tatggtacgc gagagggtcg 100200attggagtgt tatataacac tccaatcgat ctcgggttcg cctttacgcg taaaatactc 100260attggcttga acgaaatgtc gacaattccg aaatggaaca cgggacaatg gcgacggatg 100320cgcgtgtgtt agcaccagat gacatcttga attcggttgg gttgtcttct gtgcatgcgc 100380accccacagc ataaaaacta accctgtacg gttctcgcat aacctctgta gcacgcgttg 100440caccagccgc ccccagccta agtatacatg cgaccccgga gtcccgcgac gaaccgtaag 100500cgtggtattc agcaataaca ccccctgcct tgcccaactc tccaggcatc cgtgagtggg 100560tggagtcata tttgggtatg attccatgag ggccgcaaaa atatttttaa gactagacgg 100620tggtgttatg ccacgtttta cactaaacgc tagcccatgt gcatgtcccg cggtagggta 100680tggatcttga ccaataatta caacgcgaat gctctggggt ccgcaaaatc gcgtccatgc 100740aaaaatatcg cctgtagatg gaagtatttc ttcccctgaa tttaaaagac gattgtattc 100800taaaaaaata cctttcgcgt acggctcttt aagttcgtcc gacaacaggt cataccactc 100860aggggaaatg ttaaacttgc tgaaaacttc aaccgaatcc agttgcgaag agacgggggt 100920gaacgtttcc gtgtcgtaat gatgtgacat gttatttaac ttgaaggttg gggggtctag 100980cttaaccccc aaaggcagcc cgcggggtcg cttgcgggtt tttttggtaa ccggatgggc 101040caaaacataa atgtcctttg aatccgatag tttcatttca ttggcatacg cgttggaaca 101100aacggtcggc tccccagaca catccatttt ccgggatatt tgtggaagat ggagtagagt 101160ctacccatac accggaaagg gcatccaaca aagcatcgcg tatgtccccg cttttatgtt 101220cttcaccaac agattgtgtc agccccttta aggtgacgta tggatttgtc cagtacgcca 101280tttgtttgtc tttaaaccaa agtataactt ccggtactgg acattttgtc ttaaccacga 101340ttcccgatag cgcctcgctg aggtttgata ccgggggtgc cgcatagtcc cacgcctcat 101400ataccgatga cacgcacggt tccgttataa tcaaactcac atccgatagc ggtttggctc 101460caaaaaacaa cggagtgtcg tcttggagat gaagacaata cgcgattgtg atagttttta 101520aaaaaactat catctgcagt aaccatttat gtgatgccat gacgcttgtg ttttcccttc 101580actacgacgt tgtcgtatcc tttgaaaaac ttgaccactc taatggaagc atggacaagt 101640atgagtttta tatatacagt tggcctttag ttaaactctt ggtgtcatat cccattttcc 101700taaaaagggc gatcttaata tgtcaaacgt cacggcgtgc cgacaaagcg aatttccatg 101760caagatttgg atgtagtatt tatacaccca atcacacgtc acgtattaag ctttacagtc 101820ccccgttatc tgatataatc acttttctta acacgtcatc gggaaaacag atgtttatat 101880tatacctctc gcggtcattt atggcaaata cttagaccgt tttcaagcgg actgaaaacg 101940ctcaaattgc cttttggagg cctgcccaac ggccattatc ccttggatct aagattgatt 102000tgcggtaacg tttgccaatc aagctttaaa aacgtacccc aaacttaaaa cgctcaaatt 102060gccttttgga ggcctgccca acggccatta tcccttggat ctaagattga tttgcggtaa 102120cgtttgccaa acccacgcat ttcagtttaa atatttctaa gcattcttag tgcgtacttg 102180gcagcgtgct taaaatatca accaatatcc attatgctaa acgtttcctt ctatccgttt 102240caatccatta aaagtccatt accaaaaatg atgcatcata cctaattcac ctaaaaacct 102300gactcattgc agcagcgttt cctccttgca gactatccag ttggcatttt aaacgggtcc 102360ggctgcctga accgaaaaca ccgttgcctt tactgtaagt acaaaactaa aatttatatt 102420tgcgtgcgta ttttgtaaca tatatgcctt ttatcccccc gcaagtttgc tttaccctcg 102480ccttcaccac ccccgccacc ttccggccat tgtaataact ttaattgcta taagacatac 102540ccaaaccgga tgatttttgc cgctggaaaa acagcttcta attttcccgt ctcaactcgg 102600ccttggttgc atctccaagt atacctttag tttgctcccg tagaggtgta taaatacaaa 102660cggtgacaag tattgagcgt aatctcaaat ttttgtaatt tagggcggag cgcttacgac 102720agcacatgcg tactgttaga ctgttatgtt tattgtattt gcagagcagg atgccccggt 102780tactccgaga ccggattgcg ggcattccga atcgtgtacg gacttaccag ggggcagtat 102840
ttacaccttg ggttccagat ataccaaccc ttacgaccaa tagcaacact caggtatttt 102900taaaatgcac gtttaatgat cataatttac atacagttgg taataaagca gaccgtggat 102960gtttaaggca tttccttccc cctcccaaca aactaggact tcttcatctt gtttggaata 103020cctttacccg ctttaccggc agagcttttt ttggtaaggt gtttcagtga acctgatgtt 103080gatccggagg tggagggggt attggactcc ccctgtggag aggcaacttt gcgggtttta 103140cttcccttac atgccgaatc agactcagat gtcaggtcta ttgttaagca tcgtttaacg 103200tctctgccgg tatgaaataa acggcgctta gcaccccttg cgcttcccgg tttaatcccc 103260ggtaacacag aaaaaagcct gactttttgg ggtgtattta ccaatcgggt atccctttca 103320tcgccacgag aggtctcccc ggttgaggtg gtttctggtc ttacaattgg acctgtaatt 103380agttggatgg ctgtatcttt ccaggtccag gtttgcatgg ttaggcgggt tggatcggta 103440catcgatcca acaagaataa catgtttgtt acaaacggtc ctgttgaatc atgcaaaaga 103500caacgcaggg atgtttttaa tcccgcctca tcacgcccgt aaatacctat atagtttaat 103560atcaacattt ttgtaggctc tacaatttcg ggttgataca gttccgcaag ttgatcatca 103620agccatccga gtaaaggttg catgtaacac gggaatctcg cgtttccctc tgttcctcta 103680tccgtggctc gaaaaggcag tctgtccatg gttcgtgggt cttgattaat tcccacagat 103740actggacgat cacggtagtc ctgccccccg gtccggggtt gctgtgcaga ttcaatcgag 103800ccatacacca ccggggtcgc cgatcgaaca gcaggttggt ctttaaaaaa taccttccgt 103860aaaaatgatg cggtagagca tgttttggtt acaccagggc tcgagtctcg ggtcggtggt 103920tgtatagaat cctgttgaga gtcacttggt gactctgctg tgggctctct agccgacgat 103980tgaaggggcc cagggtttgg tgattgaatg ggctcccgac tcgatcttga tgttggctgt 104040tggatggact cccgactcgg tcctgggctt ggtggcagaa gatctatgac atctcccggt 104100aggatgtcga tggaatcttc aaatgacggc tcagaaaaac catcgtcgtc ggatgggtgc 104160acttcatatt ccttgtaact tgtatcactt acgatcttat gcaggatgga ttgcactgga 104220caccggcaga gaggacactg gacgctggtg gaggtccatg cccgaataca aacaaagcag 104280aagtcgtgca aacacggcat ggtttttccg agatcggaaa cggtgctcat gcatatggtg 104340caggtattat ccgaagcgtc ggaggtgccg ctaccgcccg ctaatatggt atccatggta 104400acaactggct gtattctaat gtccgggcat ccaaacacgt agcagaactg ccatgcgttc 104460taaattgtga gttgtggcga gtacattttt ataattggta ccaacgaaga cacaccccta 104520tatccctcca cccatttctt ttaagtccca cccactaaaa cgtgggtata aaatgtgtat 104580tggggtaggc ggacagtccc aacaaacagg gaagttgatt ggtataacct tgggccgggt 104640atacagctaa gtgacatttt agattctgtc tttatttaga taaagagcga tacgaagaca 104700tttctccacc cccctgtaat acccgtaaat aaaggtaagt ccacaaacaa aagcactgta 104760tataggaagt cgggtgtatt gggacagtta ctccattaga ggcgtacaga caatactggg 104820atagggtaat gcaagtcccc cccgatggtc gccccgcaaa cgcgcgggga ggtggggtcg 104880cttttttttt ttctctctcg agggggccgc gagagggccg ggccccccct cccggggtcc 104940gccgggcgcc cagaaaccgg gggggggtta ttttcggggg ggggtccgac cagcccgccc 105000gtcgcccgcc cgcacagaca gacagacact tttttcataa aaaccgttcc gcttttatta 105060acaaacaaca aacagtccgc gcgccagtgg cgctcacgag aaaaggaggg gactccgtca 105120cccccgactc tgcggggggc tcctcccccc gcgccctccc cacacatcgt cctcgtcctc 105180ggaggacgag gacgaggaca acagctccac cttgaccgcc gggcgcaagc ccacccggcg 105240gtctcgcagc acacccgggg ccaccgacac gatgctcacc ccaaaggatg accccggtgc 105300gtccccgtcg tccccgcccc cctcctcgct gtcccacgcg tcttcacacc ccacctccca 105360atcgtccagc tccaaagcgt gttctctgtc gtctgcggtg cgccgctgtc gccccgcctg 105420ggtttctgac ggccgttccg agcccccgtg gtgtccgaac acgaaccgtg ttccgtcgct 105480cccctccaac accgtctccg cggccccaaa accgggcggc cacattactc tgggaatcgg 105540ggggagggca ttccgagcct cgtccgccga cgcatacagc gccaccgacc gaccggccac 105600gggtggaagc acgagtggtt ctgcggcagg gtcgggttcc agcagggcgt ggcggcaaaa 105660caccctcgcc caggtgggta cgtcgccggc ctccggcccg gcggcccccg gtctccgtcc 105720ctcgggaagg aagacgggtc gaagcgcggc acccaggccc catcggtttg ctgcgcggtg 105780gctatgtgcc gcctcgtcca caaagtcggc tgccccgagc cccagacccc gagactgtcg 105840cgcgaggtcc ttgcaaccgt caaaacccgg cagcacgtac tgccggtatt cacggggcga 105900cagggggacg cgggtcttgg ggcccgcgcg ggtacacacg gtgtatgcga cgttcccacc 105960gcggcacaaa cacaggggtt gttcgcccgg gtacaggttg gcaaacgcag tctcgatacg 106020agcaaaactc gctggcccaa aggtgcgcga cgatgcaaac acggcccggg cgagtccttc 106080tgtgaccgcc gagtctggcc atcggacgac ggcctgggcg tccggtcgcg ccggggcccg 106140gacgtacacg tgatactgag acaaagcggg tccatccctg ggccacctct cgagggccac 106200cgcgtccaac accagcaacc ggcgccgggc agaggccaac cgcgagccta gatactcgac 106260ggccccggca aaggccaggt ctcgggtcga cagtaataaa acgccccggg cgttcaaagc 106320
ggacacgtcc ggcgggccgg tccagttccc ggcccaggca tgcgtgctcg gcaggcacaa 106380ccggttactc agggctgcca ggaccacaga cagtccccct cgggatggac tccatgacgg 106440tcccggatct gtcgcgaggg tgctctcgag ggggccgttg atgtcctctc cgggcaacgg 106500atcgtagatg atcagaagcc tcacatcctc cgggtctggg atctgccgca tccaggcgca 106560cctccgtcgc agcgcctcca ctccgctggg tggaccaaac cgtcggtctc ctccgcccgg 106620acgccgagcg gcgatttccg ccaaggcgcc gggatcaaag cttagcgcag ggcgccaggc 106680cgtgggaaac aatgggtcgt cgaccagacg ggcgatggtt tcgggggtac agtacgcctt 106740gcgagcctgg tccgacggga ccggggtatg cagggccccc cggggaatac gccgaaatcc 106800cccgtttggg gccggtccgt caagtggcat cgttattacg gcggggggat ccaccacagg 106860gcccgaggtg atggtcacgg gctcggatac ccgcctcttg gccttggaaa ccacatgatc 106920gtctgcaacc cgggcgtccg cgacgggtgt ctccctaatc ttgtcgagga ggcttctgct 106980ctcgactggc tgggacttgc gcttgcgcgg agttcgtaaa cgatcatccg gtggacacac 107040agaaagagag cgtgcggcgg ccgacggctg agggtcggga gtctgtgtgg ccggggttgt 107100tggagaaggg tgaccgcggg agatccgcgc cgccggactg gagcccgttg cctcggggta 107160tgccatgctg gcaaaggctc tgcggagact ctgtaggata aagtgttttt gggcccggtc 107220gtaccgacgg ctcatagcca cggccgcggc cgcgtggggg agagcccaga gggcctcccc 107280cgtggccatg gcttcgccta catgcggaac gggagacgct acgctccccg taacggcggt 107340acccgcccgt cccggtggca acagcttttg gtagaactgg ttcagggccg agttgacacc 107400ggtcagcttg gggttctgga gccatgctat agggtctctg tctggacagt agatcaggtt 107460aatcagcgcg cggtactgtc tagccggatc tcccaactcc ggcacgtaaa gcggcacggg 107520ttcagttgag gcctcgtaac gagcccgcgc cgctctcaca gcctcatcct cccagtgacc 107580ctctctggtc tccccggacg gtccaaaccg caccctgttg gatgggaggg gcgccgatcc 107640gggccaaggg cttccgtcgg gcatcatgag cggccccgac accgggggaa ttatcggggt 107700tctggatcgc ggcagggaaa atgatttctg tctctggcgc cccggttccc ccgcaagacg 107760tttggtctta cgaatcctcg gatcgggacc gctgatggat cgatatcccg gttggatatt 107820ttgtttcgtc gacccaccat catttgagtc cgaatcatcc gaatttgacg gggaaggggc 107880gtgttcgcgt ccggacctgc tgcctgtagt ttcacttccc accgaaacgc gccggggttc 107940atcgtcttca tcctccgatg acgatcccca cgacgaggaa gaggatgaag acgaaacaaa 108000ctcacgactc tttggctttt tctccactgg gctgtcatcc tcaatcgggt ctggtgcgtg 108060ggatcttccc ggcagggcca aaaacgctct aggtttgccc cccgacgaac gtccagggac 108120gcgaggtgtt ataccccggg catcatgttt ccttgggcgg gtatcatcgg tctcaaacgg 108180caggtccgcc tttgccccct tagcgggaac gctgtccgaa aggacgtggt acaattgctc 108240aaccgggccg ggtacaggtc caccgggttt ccgcgccggg agtgggacct taaccttcaa 108300agtctttttc ttcgggctct ttccctgagc gggccgttga gttttctgga gaactactcc 108360gtcccccgat gcatgcgcat gacccgcttg ctcatcgccc ggctttttac ccgagatgga 108420ctgagtttgt ctgtctcgat ggaccaccga cggcaaacct ggtgaatttc ctctcgtcgt 108480ttgtcggggt atagaccgct ggtcttcccg ttgatcgttc ccggcggcgt ctccaacagg 108540agacgcgggg gatacagggg agaaggcctg cgggaacgga ggggtcgtac ctctgcccgt 108600ttccccatcg ttcatcggtg gttttggaga cctagcaagc ttcgttccga gagagactgt 108660ctcgagggag cgatcggctc ctgttggttc tcgcgcgccg gcctccgaga atcgggtgtg 108720gaagacctcg gccagcggga ttacaggcga gcccattaga tcctgaccgt cctcgcatac 108780gtagtcgtct tgtgttagct cttcgccaac atcttccgtt ctgggttctg gttgaagtcc 108840cgatacggag ggaattgaaa cgatctcatg ttcccgtccc accatgaccc cgttctctcc 108900aaatagtaga tcgtcaggct gactcgaggt gaccacccgg gccctgtgtt cggcggccgc 108960ggcggccgcg tccaacaggt ccattaactc caaagtatca ggcgaccccg cgcgttgggg 109020tgtagagcgc tgcatcggcg gcgtatccat cgcactgggg tgaatttaga cgtacccgag 109080ttttccaaac gctctcgcag ccttcaaagg attgcgattg cggttggtga gggagttcca 109140acagtactta aaacgtgttg tgcccccccc tcgaccgcat atttcctccc cgtgtcgtca 109200ccgtgtaaat attcttaatg ataagacgat gtagtgattg gacgagactc gaggcgggaa 109260gttcatggac catagtatgc gtttaaggag agaccgctgg ttggcgatgt acgcccggtg 109320tctatttccg cataccttac aacatcataa caagggatac cagacatgtg aatttcattt 109380acatatgttt aaataacaac caatcatcgt gtgtctacag acgatatata atatacataa 109440acacaattgg ggttgtctca catgcaaaac atcttatata acacgggttg tttccaccca 109500tccggcatct agttaatcaa atgcacgtcg acggtgtgtt tgggtccctc tccgtcgtca 109560ttacgttcgc tcaatcaaca agcgtataca ccaccacccc tcccaacgat tatcatgtca 109620ggcggcacga agcccgcgat aacccataaa atacacacgg ggttgtggtg ttcacgtaac 109680cccccgccga tggggagggg gcgcggtacc ccgccgatgg ggagggggcg cggtaccccg 109740ccgatgggga gggggcgcgg taccccgccg atggggaggg ggcgcggtac cccgccgatg 109800
gggagggggc gcggtacccc gccgatgggg agggggcgcg gtaccccgcc gatggggagg 109860gggcgcggta ccccgccgat ggggaggggg cgcggtaccc cgccgatggg gagggggcgc 109920ggtaccccgc cgatgtttat aaccataatt ctctaaaccg ttgtagaaaa tcacaaaaaa 109980atttattcaa aaacaagtcg aagaacttca tatctgaggc atgtaaaccc attcgcactt 110040cctggggtgg aatggggtgg ggtggggggg tgaaaaaggg gggggttaaa ttgggcgtcc 110100gcatgtctgt ggtgtacgcc aatcggatac actcttttaa tctgcattcg cacttcccgt 110160tttttcactg tatgggtttt catgttttgg catgtgtcca accaccgttc gcactttctt 110220tctatatata tatatatata tatatataga gagagagaga gagagagaga gagagagaga 110280gagagaggga gagagtttct tgttcgcgcg tgttcccgcg atgtcgcggt tttatggggt 110340gtgggcgggc ttttcacaga atatatatat tccaaatgga gcggcaggct ttttaaaatc 110400gatttgacgt gataaaaaaa aaaacacacg ggccccccct ttttttggtg ttataaaggc 110460aacccaatcg aaggtctccc gccccggaat cccccattgc cattttaccc aagtagcctt 110520attcatagat gtaaacgttt gggtgtgtgt tttgttgtgc agggttcgtc cgattcataa 110580cgcgacagcg tcgagtcggt tttaagggaa aaggttacta cggccccaag gacatgtttt 110640gcacctcacc ggctacgcgg ggcgactcgt ccgagtcaaa acccggggca tcggttgatg 110700ttaacggaaa gatggaatat ggatctgcac caggacccct gaacggccgg gatacgtcgc 110760ggggccccgg cgcgttttgt actccgggtt gggagatcca cccggccagg ctcgttgagg 110820acatcaaccg tgttttttta tgtattgcac agtcgtcggg acgcgtcacg cgagattcac 110880gaagattgcg gcgcatatgc ctcgactttt atctaatggg tcgcaccaga cagcgtccca 110940cgttagcgtg ctgggaggaa ttgttacagc ttcaacccac ccagacgcag tgcttacgcg 111000ctactttaat ggaagtgtcc catcgacccc ctcgggggga agacgggttc attgaggcgc 111060cgaatgttcc tttgcatagg agcgcactgg aatgtgacgt atctgatgat ggtggtgaag 111120acgatagcga cgatgatggg tctacgccat cggatgtaat tgaatttcgg gattccgacg 111180cggaatcatc ggacggggaa gactttatag tggaagaaga atcagaggag agcaccgatt 111240cttgtgaacc agacggggta cccggcgatt gttatcgaga cggggatggg tgcaacaccc 111300cgtccccaaa gagaccccag cgtgccatcg agcgatacgc gggtgcagaa accgcggaat 111360atacggccgc gaaagcgctc accgcgttgg gcgagggggg tgtagattgg aagcgacgtc 111420gacacgaagc cccgcgccgg catgatatac cgccccccca tggcgtgtag tctttataaa 111480taaatacaat ggtttggctc gtgtcttttt ttgatgtctg tctgtggggg agtggggtgt 111540tgtggatatt agagggtaga gggtgctggt ttgaacgtct ccattaaccc acggggtccc 111600cacacgggcc gtgtggtatg aatctctgcg gatcccgcgg tgagcacccg ggcggtgaat 111660atgccggact ttactgcaca cgacacgata cccccgcgca ccaggctctc atgaacgacg 111720ccgaacggta cttcgccgcc gcgctatgcg ccatatctac cgaggcctac gaggctttta 111780tacacagccc ctccgagaga ccgtgcgcga gtttgtgggg gagggcaaag gacgccttcg 111840gacggatgtg cggggagctc gcagcggata gacaacgtcc accctcggtt ccgccgatcc 111900gcagagcggt gttatcgtta ttacgcgagc aatgcatgcc ggatccacaa tcgcatctgg 111960agctcagcga gcggctgata ttgatggcat attggtgctg tttgggacac gccggacttc 112020cgactattgg attgtcgccc gataataaat gcatccgcgc cgaattatat gaccgccccg 112080ggggaatttg tcacaggctt tttgacgcgt acctgggctg cgggtccctt ggagtcccaa 112140gaacctacga gagatcctga caccccatcc ctttatatag aaaaaaaaaa ataaatttaa 112200aacatacacc ggataaaagc gtactgtttt ttatttaaat ttacacgctc gacgttgccc 112260cggttcggtg atcaccgggt cttatctata tacaccgtgt aactcgaacc cccgtgactc 112320cctccaatcg cgttaccaaa ctcttcttcc gtatccgtag attccgagtc ctcgaaatcg 112380tccacttatc caacaaattg tgacgttata tatcccaagg caaaggccgc tcccgtcata 112440gcaaatacaa agacaattat tagcgtaata taacagaatt ttttacgatg atatatttta 112500tgttgatatt ttccaattcg acgcaaaaat tcatctgccg tttcattttc gctatcacta 112560taataacact tttcagccga acggctcggt tgtatggctg ttatcgttgt attatttggt 112620tgcgctcgcg gggttaccac cgcttccatc agtaaggcca cggcctcacc ctccatggtg 112680ttttgtccgg ccatagaaat ccagattgta aggccagcag gctagtttaa aagtgtttaa 112740taccacacct tttgatattt atatacatgc aagattctag attattcatc aataggtcgt 112800ttaaagcgcg ttttcataaa cgttgtcagc tataccgaca ttctcacaaa gaggtaaagt 112860taccttacgt tattattaaa taaaacatgt agacattatt aataatccta ggaacaatca 112920aatccatatt tgtaagttat gtttaacccc tccccttttt gtcattatct ccgccctctt 112980ataatcggat cactttataa gtgtgtcggt gagtatattt tgtacagttg ttggacaaca 113040ggtttttggt tcattaacac tatcaacata agtcggggta tacaagtata atgaacgacg 113100ttgatgcaac agacaccttt gttggacaag gaaagttccg tggcgccatc tcaacatcac 113160cgtcacatat tatgcaaaca tgtgggttta tacaacagat gtttccagtt gaaatgtcgc 113220ccggcataga atctgaggat gatcccaatt atgacgttaa catggatata cagtctttta 113280
atatatttga tggtgtacac gaaactgaag ccgaagcctc tgtggcattg tgcgcagaag 113340cacgcgttgg aattaataaa gcgggatttg taatattaaa aacgtttaca ccaggggcgg 113400aaggttttgc gtttgcgtgt atggacagta aaacatgtga acatgtggtc attaaagcgg 113460gtcaacgtca aggaacggcc accgaggcaa ccgtgttaag agcgttaacc cacccatccg 113520ttgtacagct taaaggaacg tttacgtata acaaaatgac atgtcttata ttaccacgtt 113580accgaacaga tttatactgc tatctagctg caaagcgcaa cctccccata tgtgacattt 113640tagcaattca gcgatctgta ttacgcgcgt tacagtatct tcataataac agtattattc 113700accgtgatat aaaatctgaa aatatattta ttaaccaccc aggtgatgtt tgtgtgggag 113760actttggagc agcgtgtttc cccgtggata ttaatgccaa caggtattat ggctgggctg 113820gaacaatcgc cacaaactct cctgagttat tggctagaga tccatatgga cctgccgtgg 113880acatatggag tgccgggatt gtattatttg aaatggctac aggacagaac tcgttatttg 113940aacgagacgg tttagatggc aattgtgaca gtgagcgtca aattaaactt attatacgac 114000gatctggaac tcatcccaat gaatttccca ttaaccctac atcaaatctt cgtcgacaat 114060acattggttt ggcaaaacgg tcttctcgaa aacccggatc caggccattg tggacaaatc 114120tatatgagtt gccaattgat ttggagtatt tgatatgtaa gatgttatcg tttgacgcac 114180gtcatcgacc atcggcagag gtgttgctta accactctgt tttccaaact cttcccgatc 114240catatccaaa tccaatggaa gttggagatt aaaattcatt aagcctgtta ataaaatatt 114300gtataaattg tgtttataac gtataacccg ttaaggcaaa tagggtacaa acgcgcaatg 114360ttttgaaata ctaatataaa taacataacc aatagaaact taatacagag tcacgcccca 114420ttacaacaag gataaaacac gggatcattt tcttaacatt gtagtagcgc tgaaaagcgt 114480cccctccccc ggctcacaga gctgctcttc ggtgtagttg ggtatactgg tgcgcctcat 114540ttaatcgcga tgtttttaat ccaatgtttg atatcggccg ttatatttta catacaagtg 114600accaacgctt tgatcttcaa gggcgaccac gtgagcttgc aagttaacag cagtctcacg 114660tctatcctta ttcccatgca aaatgataat tatacagaga taaaaggaca gcttgtcttt 114720attggagagc aactacctac cgggacaaac tatagcggaa cactggaact gttatacgcg 114780gatacggtgg cgttttgttt ccggtcagta caagtaataa gatacgacgg atgtccccgg 114840attagaacga gcgcttttat ttcgtgtagg tacaaacatt cgtggcatta tggtaactca 114900acggatcgga tatcaacaga gccggatgct ggtgtaatgt tgaaaattac caaaccggga 114960ataaatgatg ctggtgtgta tgtacttctt gttcggttag accatagcag atccaccgat 115020ggtttcattc ttggtgtaaa tgtatataca gcgggctcgc atcacaacat tcacggggtt 115080atctacactt ctccatctct acagaatgga tattctacaa gagccctttt tcaacaagct 115140cgtttgtgtg atttacccgc gacacccaaa gggtccggta cctccctgtt tcaacatatg 115200cttgatcttc gtgccggtaa atcgttagag gataaccctt ggttacatga ggacgttgtt 115260acgacagaaa ctaagtccgt tgttaaggag gggatagaaa atcacgtata tccaacggat 115320atgtccacgt tacccgaaaa gtcccttaat gatcctccag aaaatctact tataattatt 115380cctatagtag cgtctgtcat gatcctcacc gccatggtta ttgttattgt aataagcgtt 115440aagcgacgta gaattaaaaa acatccaatt tatcgcccaa atacaaaaac aagaaggggc 115500atacaaaatg cgacaccaga atccgatgtg atgttggagg ccgccattgc acaactagca 115560acgattcgcg aagaatcccc cccacattcc gttgtaaacc cgtttgttaa atagaactaa 115620ttatcccgga ttttatatta aataaactat atgcgtttta tttagcgttt tgattacgcg 115680ttgtgatatg aggggaagga ttaagaatct cctaactata agttaacacg cccacatttg 115740ggcggggatg ttttatgaag ccttaaaggc cgagctggta tacacgagag cagtccatgg 115800ttttagacct cgggcgaatt gcgtggtttt aagtgactat attccgaggg tcgcctgtaa 115860tatggggaca gttaataaac ctgtggtggg ggtattgatg gggttcggaa ttatcacggg 115920aacgttgcgt ataacgaatc cggtcagagc atccgtcttg cgatacgatg attttcacat 115980cgatgaagac aaactggata caaactccgt atatgagcct tactaccatt cagatcatgc 116040ggagtcttca tgggtaaatc ggggagagtc ttcgcgaaaa gcgtacgatc ataactcacc 116100ttatatatgg ccacgtaatg attatgatgg atttttagag aacgcacacg aacaccatgg 116160ggtgtataat cagggccgtg gtatcgatag cggggaacgg ttaatgcaac ccacacaaat 116220gtctgcacag gaggatcttg gggacgatac gggcatccac gttatcccta cgttaaacgg 116280cgatgacaga cataaaattg taaatgtgga ccaacgtcaa tacggtgacg tgtttaaagg 116340agatcttaat ccaaaacccc aaggccaaag actcattgag gtgtcagtgg aagaaaatca 116400cccgtttact ttacgcgcac cgattcagcg gatttatgga gtccggtaca ccgagacttg 116460gagctttttg ccgtcattaa cctgtacggg agacgcagcg cccgccatcc agcatatatg 116520tttaaaacat acaacatgct ttcaagacgt ggtggtggat gtggattgcg cggaaaatac 116580taaagaggat cagttggccg aaatcagtta ccgttttcaa ggtaagaagg aagcggacca 116640accgtggatt gttgtaaaca cgagcacact gtttgatgaa ctcgaattag acccccccga 116700gattgaaccg ggtgtcttga aagtacttcg gacagaaaaa caatacttgg gtgtgtacat 116760
ttggaacatg cgcggctccg atggtacgtc tacctacgcc acgtttttgg tcacctggaa 116820aggggatgaa aaaacaagaa accctacgcc cgcagtaact cctcaaccaa gaggggctga 116880gtttcatatg tggaattacc actcgcatgt attttccgtt ggtgatacgt ttagcttggc 116940aatgcatctt cagtataaga tacatgaagc gccatttgat ttgctgttag agtggttgta 117000tgtccccatc gatcctacat gtcaaccaat gcggttatat tctacgtgtt tgtatcatcc 117060caacgcaccc caatgcctct ctcatatgaa ttccggttgt acatttacct cgccacattt 117120agcccagcgt gttgcaagca cagtgtatca aaattgtgaa catgcagata actacaccgc 117180atattgtctg ggaatatctc atatggagcc tagctttggt ctaatcttac acgacggggg 117240caccacgtta aagtttgtag atacacccga gagtttgtcg ggattatacg tttttgtggt 117300gtattttaac gggcatgttg aagccgtagc atacactgtt gtatccacag tagatcattt 117360tgtaaacgca attgaagagc gtggatttcc gccaacggcc ggtcagccac cggcgactac 117420taaacccaag gaaattaccc ccgtaaaccc cggaacgtca ccacttctac gatatgccgc 117480atggaccgga gggcttgcag cagtagtact tttatgtctc gtaatatttt taatctgtac 117540ggctaaacga atgagggtta aagcctatag ggtagacaag tccccgtata accaaagcat 117600gtattacgct ggccttccag tggacgattt cgaggactcg gaatctacgg atacggaaga 117660agagtttggt aacgcgattg gagggagtca cgggggttcg agttacacgg tgtatataga 117720taagacccgg tgatcaccga accggggcaa cgtcgagcgt gtaaatttaa ataaaaaaca 117780gtacgctttt atccggtgta tgttttaaat ttattttttt ttttctatat aaagggatgg 117840ggtgtcagga tctctcgtag gttcttggga ctccaaggga cccgcagccc aggtacgcgt 117900caaaaagcct gtgacaaatt cccccggggc ggtcatataa ttcggcgcgg atgcatttat 117960tatcgggcga caatccaata gtcggaagtc cggcgtgtcc caaacagcac caatatgcca 118020tcaatatcag ccgctcgctg agctccagat gcgattgtgg atccggcatg cattgctcgc 118080gtaataacga taacaccgct ctgcggatcg gcggaaccga gggtggacgt tgtctatccg 118140ctgcgagctc cccgcacatc cgtccgaagg cgtcctttgc cctcccccac aaactcgcgc 118200acggtctctc ggaggggctg tgtataaaag cctcgtaggc ctcggtagat atggcgcata 118260gcgcggcggc gaagtaccgt tcggcgtcgt tcatgagagc ctggtgcgcg ggggtatcgt 118320gtcgtgtgca gtaaagtccg gcatattcac cgcccgggtg ctcaccgcgg gatccgcaga 118380gattcatacc acacggcccg tgtggggacc ccgtgggtta atggagacgt tcaaaccagc 118440accctctacc ctctaatatc cacaacaccc cactccccca cagacagaca tcaaaaaaag 118500acacgagcca aaccattgta tttatttata aagactacac gccatggggg ggcggtatat 118560catgccggcg cggggcttcg tgtcgacgtc gcttccaatc tacacccccc tcgcccaacg 118620cggtgagcgc tttcgcggcc gtatattccg cggtttctgc acccgcgtat cgctcgatgg 118680cacgctgggg tctctttggg gacggggtgt tgcacccatc cccgtctcga taacaatcgc 118740cgggtacccc gtctggttca caagaatcgg tgctctcctc tgattcttct tccactataa 118800agtcttcccc gtccgatgat tccgcgtcgg aatcccgaaa ttcaattaca tccgatggcg 118860tagacccatc atcgtcgcta tcgtcttcac caccatcatc agatacgtca cattccagtg 118920cgctcctatg caaaggaaca ttcggcgcct caatgaaccc gtcttccccc cgagggggtc 118980gatgggacac ttccattaaa gtagcgcgta agcactgcgt ctgggtgggt tgaagctgta 119040acaattcctc ccagcacgct aacgtgggac gctgtctggt gcgacccatt agataaaagt 119100cgaggcatat gcgccgcaat cttcgtgaat ctcgcgtgac gcgtcccgac gactgtgcaa 119160tacataaaaa aacacggttg atgtcctcaa cgagcctggc cgggtggatc tcccaacccg 119220gagtacaaaa cgcgccgggg ccccgcgacg tatcccggcc gttcaggggt cctggtgcag 119280atccatattc catctttccg ttaacatcaa ccgatgcccc gggttttgac tcggacgagt 119340cgccccgcgt agccggtgag gtgcaaaaca tgtccttggg gccgtagtaa ccttttccct 119400taaaaccgac tcgacgctgt cgcgttatga atcggacgaa ccctgcacaa caaaacacac 119460acccaaacgt ttacatctat gaataaggct acttgggtaa aatggcaatg ggggattccg 119520gggcgggaga ccttcgattg ggttgccttt ataacaccaa aaaaaggggg ggcccgtgtg 119580tttttttttt tatcacgtca aatcgatttt aaaaagcctg ccgctccatt tggaatatat 119640atattctgtg aaaagcccgc ccacacccca taaaaccgcg acatcgcggg aacacgcgcg 119700aacaagaaac tctctccctc tctctctctc tctctctctc tctctctctc tctctctata 119760tatatatata tatatatata tagaaagaaa gtgcgaacgg tggttggaca catgccaaaa 119820catgaaaacc catacagtga aaaaacggga agtgcgaatg cagattaaaa gagtgtatcc 119880gattggcgta caccacagac atgcggacgc ccaatttaac cccccccttt ttcacccccc 119940caccccaccc cattccaccc caggaagtgc gaatgggttt acatgcctca gatatgaagt 120000tcttcgactt gtttttgaat aaattttttt gtgattttct acaacggttt agagaattat 120060ggttataaac atcggcgggg taccgcgccc cctccccatc ggcggggtac cgcgccccct 120120ccccatcggc ggggtaccgc gccccctccc catcggcggg gtaccgcgcc ccctccccat 120180cggcggggta ccgcgccccc tccccatcgg cggggtaccg cgccccctcc ccatcggcgg 120240
ggtaccgcgc cccctcccca tcggcggggt accgcgcccc ctccccatcg gcggggtacc 120300gcgccccctc cccatcggcg gggggttacg tgaacaccac aaccccgtgt gtattttatg 120360ggttatcgcg ggcttcgtgc cgcctgacat gataatcgtt gggaggggtg gtggtgtata 120420cgcttgttga ttgagcgaac gtaatgacga cggagaggga cccaaacaca ccgtcgacgt 120480gcatttgatt aactagatgc cggatgggtg gaaacaaccc gtgttatata agatgttttg 120540catgtgagac aaccccaatt gtgtttatgt atattatata tcgtctgtag acacacgatg 120600attggttgtt atttaaacat atgtaaatga aattcacatg tctggtatcc cttgttatga 120660tgttgtaagg tatgcggaaa tagacaccgg gcgtacatcg ccaaccagcg gtctctcctt 120720aaacgcatac tatggtccat gaacttcccg cctcgagtct cgtccaatca ctacatcgtc 120780ttatcattaa gaatatttac acggtgacga cacggggagg aaatatgcgg tcgagggggg 120840ggcacaacac gttttaagta ctgttggaac tccctcacca accgcaatcg caatcctttg 120900aaggctgcga gagcgtttgg aaaactcggg tacgtctaaa ttcaccccag tgcgatggat 120960acgccgccga tgcagcgctc tacaccccaa cgcgcggggt cgcctgatac tttggagtta 121020atggacctgt tggacgcggc cgccgcggcc gccgaacaca gggcccgggt ggtcacctcg 121080agtcagcctg acgatctact atttggagag aacggggtca tggtgggacg ggaacatgag 121140atcgtttcaa ttccctccgt atcgggactt caaccagaac ccagaacgga agatgttggc 121200gaagagctaa cacaagacga ctacgtatgc gaggacggtc aggatctaat gggctcgcct 121260gtaatcccgc tggccgaggt cttccacacc cgattctcgg aggccggcgc gcgagaacca 121320acaggagccg atcgctccct cgagacagtc tctctcggaa cgaagcttgc taggtctcca 121380aaaccaccga tgaacgatgg ggaaacgggc agaggtacga cccctccgtt cccgcaggcc 121440ttctcccctg tatcccccgc gtctcctgtt ggagacgccg ccgggaacga tcaacgggaa 121500gaccagcggt ctataccccg acaaacgacg agaggaaatt caccaggttt gccgtcggtg 121560gtccatcgag acagacaaac tcagtccatc tcgggtaaaa agccgggcga tgagcaagcg 121620ggtcatgcgc atgcatcggg ggacggagta gttctccaga aaactcaacg gcccgctcag 121680ggaaagagcc cgaagaaaaa gactttgaag gttaaggtcc cactcccggc gcggaaaccc 121740ggtggacctg tacccggccc ggttgagcaa ttgtaccacg tcctttcgga cagcgttccc 121800gctaaggggg caaaggcgga cctgccgttt gagaccgatg atacccgccc aaggaaacat 121860gatgcccggg gtataacacc tcgcgtccct ggacgttcgt cggggggcaa acctagagcg 121920tttttggccc tgccgggaag atcccacgca ccagacccga ttgaggatga cagcccagtg 121980gagaaaaagc caaagagtcg tgagtttgtt tcgtcttcat cctcttcctc gtcgtgggga 122040tcgtcatcgg aggatgaaga cgatgaaccc cggcgcgttt cggtgggaag tgaaactaca 122100ggcagcaggt ccggacgcga acacgcccct tccccgtcaa attcggatga ttcggactca 122160aatgatggtg ggtcgacgaa acaaaatatc caaccgggat atcgatccat cagcggtccc 122220gatccgagga ttcgtaagac caaacgtctt gcgggggaac cggggcgcca gagacagaaa 122280tcattttccc tgccgcgatc cagaaccccg ataattcccc cggtgtcggg gccgctcatg 122340atgcccgacg gaagcccttg gcccggatcg gcgcccctcc catccaacag ggtgcggttt 122400ggaccgtccg gggagaccag agagggtcac tgggaggatg aggctgtgag agcggcgcgg 122460gctcgttacg aggcctcaac tgaacccgtg ccgctttacg tgccggagtt gggagatccg 122520gctagacagt accgcgcgct gattaacctg atctactgtc cagacagaga ccctatagca 122580tggctccaga accccaagct gaccggtgtc aactcggccc tgaaccagtt ctaccaaaag 122640ctgttgccac cgggacgggc gggtaccgcc gttacgggga gcgtagcgtc tcccgttccg 122700catgtaggcg aagccatggc cacgggggag gccctctggg ctctccccca cgcggccgcg 122760gccgtggcta tgagccgtcg gtacgaccgg gcccaaaaac actttatcct acagagtctc 122820cgcagagcct ttgccagcat ggcatacccc gaggcaacgg gctccagtcc ggcggcgcgg 122880atctcccgcg gtcacccttc tccaacaacc ccggccacac agactcccga ccctcagccg 122940tcggccgccg cacgctctct ttctgtgtgt ccaccggatg atcgtttacg aactccgcgc 123000aagcgcaagt cccagccagt cgagagcaga agcctcctcg acaagattag ggagacaccc 123060gtcgcggacg cccgggttgc agacgatcat gtggtttcca aggccaagag gcgggtatcc 123120gagcccgtga ccatcacctc gggccctgtg gtggatcccc ccgccgtaat aacgatgcca 123180cttgacggac cggccccaaa cgggggattt cggcgtattc cccggggggc cctgcatacc 123240ccggtcccgt cggaccaggc tcgcaaggcg tactgtaccc ccgaaaccat cgcccgtctg 123300gtcgacgacc cattgtttcc cacggcctgg cgccctgcgc taagctttga tcccggcgcc 123360ttggcggaaa tcgccgctcg gcgtccgggc ggaggagacc gacggtttgg tccacccagc 123420ggagtggagg cgctgcgacg gaggtgcgcc tggatgcggc agatcccaga cccggaggat 123480gtgaggcttc tgatcatcta cgatccgttg cccggagagg acatcaacgg ccccctcgag 123540agcaccctcg cgacagatcc gggaccgtca tggagtccat cccgaggggg actgtctgtg 123600gtcctggcag ccctgagtaa ccggttgtgc ctgccgagca cgcatgcctg ggccgggaac 123660tggaccggcc cgccggacgt gtccgctttg aacgcccggg gcgttttatt actgtcgacc 123720
cgagacctgg cctttgccgg ggccgtcgag tatctaggct cgcggttggc ctctgcccgg 123780cgccggttgc tggtgttgga cgcggtggcc ctcgagaggt ggcccaggga tggacccgct 123840ttgtctcagt atcacgtgta cgtccgggcc ccggcgcgac cggacgccca ggccgtcgtc 123900cgatggccag actcggcggt cacagaagga ctcgcccggg ccgtgtttgc atcgtcgcgc 123960acctttgggc cagcgagttt tgctcgtatc gagactgcgt ttgccaacct gtacccgggc 124020gaacaacccc tgtgtttgtg ccgcggtggg aacgtcgcat acaccgtgtg tacccgcgcg 124080ggccccaaga cccgcgtccc cctgtcgccc cgtgaatacc ggcagtacgt gctgccgggt 124140tttgacggtt gcaaggacct cgcgcgacag tctcggggtc tggggctcgg ggcagccgac 124200tttgtggacg aggcggcaca tagccaccgc gcagcaaacc gatggggcct gggtgccgcg 124260cttcgacccg tcttccttcc cgagggacgg agaccggggg ccgccgggcc ggaggccggc 124320gacgtaccca cctgggcgag ggtgttttgc cgccacgccc tgctggaacc cgaccctgcc 124380gcagaaccac tcgtgcttcc acccgtggcc ggtcggtcgg tggcgctgta tgcgtcggcg 124440gacgaggctc ggaatgccct ccccccgatt cccagagtaa tgtggccgcc cggttttggg 124500gccgcggaga cggtgttgga ggggagcgac ggaacacggt tcgtgttcgg acaccacggg 124560ggctcggaac ggccgtcaga aacccaggcg gggcgacagc ggcgcaccgc agacgacaga 124620gaacacgctt tggagctgga cgattgggag gtggggtgtg aagacgcgtg ggacagcgag 124680gaggggggcg gggacgacgg ggacgcaccg gggtcatcct ttggggtgag catcgtgtcg 124740gtggccccgg gtgtgctgcg agaccgccgg gtgggcttgc gcccggcggt caaggtggag 124800ctgttgtcct cgtcctcgtc ctccgaggac gaggacgatg tgtggggagg gcgcgggggg 124860aggagccccc cgcagagtcg ggggtgacgg agtcccctcc ttttctcgtg agcgccactg 124920gcgcgcggac tgtttgttgt ttgttaataa aagcggaacg gtttttatga aaaaagtgtc 124980tgtctgtctg tgcgggcggg cgacgggcgg gctggtcgga cccccccccg aaaataaccc 125040ccccccggtt tctgggcgcc cggcggaccc cgggaggggg ggcccggccc tctcgcggcc 125100ccctcgagag agaaaaaaaa aaa 12512權利要求
1.一種水痘-帶狀皰疹病(Varicella-herpes Zoster virus)毒株,其保藏編號為CGMCC No.1618。
2.權利要求1所述的水痘-帶狀皰疹病毒株,其基因組中的R2可變區重複單位的拷貝數為7個,R4可變區重複單位的拷貝數為9個,R5可變區為1個。
3.權利要求2所述的水痘-帶狀皰疹病毒株,其基因組全長125123bp,G+C含量為46.1%。
4.權利要求3所述的水痘-帶狀皰疹病毒株,其核苷酸序列如序列表中序列1所示。
5.一種減毒水痘活疫苗,其由權利要求1-4中任一項所述的毒株製備而來。
6.權利要求5所述的疫苗,其為凍幹劑型。
7.權利要求5所述的疫苗,其為液體劑型。
8.一種製備減毒水痘活疫苗的方法,包括如下步驟a)宿主細胞的培養步驟;在該步驟中,在pH6.8-7.0的含有10%小牛血清的液體培養基中使宿主細胞擴增傳代;b)病毒的接種、生長步驟;該步驟如下完成棄去步驟a)中所用的培養液,用權利要求1-4中任一項所述的毒株感染步驟a)獲得的宿主細胞並使接種了病毒的宿主細胞在pH7.2-7.4的含有2%牛血清的液體培養基中維持生長的步驟;c)病毒的增殖步驟;即棄去步驟b)所用的培養液並使步驟b)得到的培養物在含有0.05-0.5%人白蛋白的液體培養基中培養以使病毒進一步增殖;以及d)收穫步驟c)培養的病毒的步驟。
9.權利要求8所述的方法,其中步驟b)的感染複數M.O.I.為0.01-1。
10.權利要求8所述的方法,其中所述的液體培養基為選自MEM,DMEM,199、RPMI1640、Eagle’s、Earle’s中的任一種培養液。
11.權利要求8所述的方法,其中步驟在步驟b)和步驟c)之間還包括用PBS、生理鹽水、Earle’s液或Eagle’s液對培養細胞進行衝洗的步驟。
12.權利要求8所述的方法,其中所述的步驟d)是如下進行的在細胞的病變程度達至少75%時,吸出所述液體培養液,加入保護劑後,破碎細胞,去除細胞碎片,獲得疫苗原液。
13.權利要求8-12所述的方法,其中所述的宿主細胞為2BS細胞。
全文摘要
本發明的目的在於提供一種可用於水痘疫苗生產的新的水痘-帶狀皰疹病毒,使用該病毒製備水痘疫苗以及用該病毒製備水痘疫苗的方法。該新的水痘-帶狀皰疹病毒株的保藏編號為CGMCC No.1618。
文檔編號C12N7/04GK101082041SQ200610083049
公開日2007年12月5日 申請日期2006年5月29日 優先權日2006年5月29日
發明者李秀玲, 王桂秋, 王用楫, 章以浩, 項金忠, 許麗鋒, 彭佩霞, 龐成華, 謝雲, 張晨, 劉立新 申請人:北京生物製品研究所

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