CN101184839A - 用于呼吸道病毒感染的RNAi治疗 - Google Patents

Abstract

此处公开了抑制呼吸道病毒繁殖的双链siRNA分子及其用途，其中所述siRNA分子的每条链约15至约50个核苷酸，并且其中所述siRNA分子的一条链包括与该呼吸道病毒核酸序列中保守位点或其变体相同的核酸序列。

Description

用于呼吸道病毒感染的RNAi治疗

序列表

用于本申请的序列表提交于代替印刷纸件的高密度磁盘，该盘记录于2006年9月1日并标记为CRF“Copyl”、“Copy2”和“Copy3”，每个盘仅含有名为“0525PCT.APP”的1.68 MB文件，其在此以引用的方式整体并入本文。

发明领域

本发明一般涉及治疗和预防病毒感染的领域。本发明还涉及使用RNA干扰(RNAi)，尤其是抗病毒siRNA和shRNA的领域。

发明背景

RNA干扰(RNAi)是植物和动物中普遍存在的一种基因调节机制，其中靶mRNA以序列特异性的方式降解(Sharp，P.A.，Genes Dev.15，485-490(2001)；Hutvagner，G .& Zamore，P.D.，Cuur.Opin.Genet.Dev.12，225-232(2002)；Fire，A.，等，Nature 391，806-811(1998)；Zamore，P.，等，Cell101，25-33(2000))。靶mRNA可为宿主mRNA或宿主病原体如病毒病原体的mRNA。

致病性病毒感染是一些世界范围最广泛传播的感染。这种病毒的一个家族是流感家族。在1918年甲型流感病毒大流行期间，估计有2000万至4000万人死亡。在美国，每年有2万至4万人死于甲型流感或其并发症。流行病期间，仅一个冬季流感相关送院的数目就达到超过300,000。对流感病毒感染没有较好的治疗方案，现有的疫苗效价有限，部分是因为抗原性转变和抗原性漂移的特征。大量其它对人类和其它动物致病的病毒的治疗或预防面临类似的困难。

天然RNA降解过程由dsRNA(双链RNA)特异性核酸内切酶Dicer起始，所述内切酶Dicer促进长dsRNA前体持续裂解为21至25核苷酸长的双链片段，该片段称为小干扰RNA(siRNA)(Zamore，P.，等，Cell 101，25-33(2000)；Elbashir，S.M.，等，Genes Dev.15，188-200(2001)；Hammond，S.M.，等，Nature 404，293-296(2000)；Bemstein，E.，等，Nature 409，363-366(2001))。siRNA并入长蛋白质复合体，其识别和裂解靶mRNA(Nykanen，A.，等，Cell 107，309-321(2001))。有研究组报道，dsRNA引入哺乳动物细胞不导致有效的Dicer-介导的siRNA产生，并因此不诱导RNAi(Caplen，N.J.，等，Gene 252，95-105(2000)；Ui-Tei，K.，等，FEBS Lett.479，79-82(2000))。siRNA在细胞中成熟中对Dicer的需求可通过引入合成寡核苷酸siRNA双链体(如21核苷酸序列)而迂回，该双链体在多种哺乳动物细胞中抑制转染基因和内源基因的表达(Elbashir，等，Nature411：494-498(2001))。

发明内容

在阅读了本发明以下更完全的描述之后，本领域技术人员对本发明的这些和其它目标、优点和特征将更加显而易见。当提供数值的一个范围时，应理解还特定地公布了该范围上限值和下限值之间每个内插值，除非上下文另有清楚指明，所述内插值以下限值的十分之一为单位增量。在指明范围中的任何指明值或内插值与该指明范围中的任何其它指明值或内插值之间的每个较小范围也都包括在本发明中。根据指明范围中任何具体排除的界限，这些较小范围的上限值和下限值可独立地包括在该范围内或排除于该范围外，且两个限值中任一个或两个都包括在所述较小范围内或两个都没有包括在所述较小范围内时每个范围也都包括在本发明中。当所指明范围包括两个限值的一个或两个时，排除了所包括的限值的任何一个或两个的那些范围也包括在本发明中。

本发明的一方面是一种诱导RNAi的实体，其靶向于呼吸道病毒的转录子，其中所述诱导RNAi的实体长度在约15和约60个核苷酸之间，并包括：至少84％相同于编码病毒蛋白的核酸的一部分的第一核酸序列；和至少84％互补于所述第一核酸部分的第二核酸序列。

在本发明的一个实施方案中，所述诱导RNAi的实体长度在约15和约40个核苷酸之间，并包括：至少89％相同于编码病毒蛋白的核酸的一部分的第一核酸序列；和至少89％互补于所述第一核酸部分的第二核酸序列。在本发明另一实施方案中，所述诱导RNAi的实体长度在约15和约40个核苷酸之间，并包括：至少94％相同于编码病毒蛋白的核酸的一部分的第一核酸序列；和至少94％互补于所述第一核酸部分的第二核酸序列。在另一实施方案中，所述诱导RNAi的实体是siRNA或shRNA。在本发明另一实施方案中，该核酸包括3’突出端。在相关实施方案中，3，突出端包括脱氧胸苷。在本发明另一实施方案中，病毒蛋白获自选自人类呼吸道合胞病毒、人类偏肺病毒、1型人类副流感病毒、2型人类副流感病毒、3型人类副流感病毒、4a型人类副流感病毒、4b型人类副流感病毒、鼻病毒和流感病毒的病毒。在本发明另一实施方案中，病毒蛋白是呼吸道病毒蛋白。在本发明另一实施方案中，病毒蛋白是流感病毒蛋白。在本发明另一实施方案中，诱导RNAi的实体是shRNA，进一步包括形成发夹环结构的第三核酸序列。在相关实施方案中，发夹环结构包括4至11个核苷酸。

本发明的另一方面是分离的核酸序列，长约16至约35个核苷酸，沿其长度至少约85％相同于编码病毒蛋白的病毒核酸的一部分或其互补物。在本发明一个实施方案中，病毒蛋白获自选自人类呼吸道合胞病毒、人类偏肺病毒、1型人类副流感病毒、2型人类副流感病毒、3型人类副流感病毒、4a型人类副流感病毒、4b型人类副流感病毒、鼻病毒和流感病毒的病毒。在本发明另一实施方案中，病毒蛋白是呼吸道病毒蛋白。在本发明另一实施方案中，病毒蛋白是流感病毒蛋白。

本发明的另一方面是诱导RNAi的实体，其靶向流感病毒蛋白的转录子，其中所述诱导RNAi的实体长度在约15和约60个核苷酸之间，并包括：

第一核酸序列，其包括选自以下一组的核酸序列：SEQ ID NO 1-10709、其互补物、或其长度有至少16个核苷酸或核苷酸序列至少80％同源于所述核酸序列的片段；和

第二核酸序列，其至少80％互补于所述第一核酸序列。

在本发明另一实施方案中，所述第二核酸序列至少约90％互补于所述第一核酸部分。在另一实施方案中，所述诱导RNAi的实体是siRNA或shRNA。在本发明另一实施方案中，诱导RNAi的实体是shRNA，进一步包括形成发夹环结构的第三核酸序列。在相关实施方案中，发夹环结构包括4至11个核苷酸。

本发明的另一方面是靶向病毒蛋白转录子保守位点的siRNA，其中所述诱导RNAi的实体长度约15至约60个核苷酸。在本发明另一实施方案中，保守位点长度约300个核苷酸，并包括所述病毒蛋白基因的3’末端。在本发明另一实施方案中，病毒蛋白获自选自人类呼吸道合胞病毒、人类偏肺病毒、1型人类副流感病毒、2型人类副流感病毒、3型人类副流感病毒、4a型人类副流感病毒、4b型人类副流感病毒、鼻病毒和流感病毒的病毒。在本发明另一实施方案中，病毒蛋白是呼吸道病毒蛋白。在本发明另一实施方案中，病毒蛋白是流感病毒蛋白。

本发明的另一方面是siRNA，其减少编码第一病毒蛋白的第一基因和编码第二病毒蛋白的第二基因的表达。在本发明一个实施方案中，第一病毒基因和第二病毒基因来自同一病毒的不同毒株。在本发明另一实施方案中，第一病毒基因和第二病毒基因来自两种不同病毒。在相关实施方案中，一种病毒是流感病毒。

本发明的另一方面是减少编码病毒蛋白的两个或多个基因的表达至少约25％的siRNA。

本发明的另一方面是RNAi诱导剂，其靶向转录子，该转录子的序列包括编码病毒蛋白的核酸的靶部分。在本发明一实施方案中，该RNAi诱导剂是siRNA或shRNA。在本发明另一实施方案中，病毒蛋白获自选自人类呼吸道合胞病毒、人类偏肺病毒、1型人类副流感病毒、2型人类副流感病毒、3型人类副流感病毒、4a型人类副流感病毒、4b型人类副流感病毒、鼻病毒和流感病毒的病毒。在本发明另一实施方案中，病毒蛋白是呼吸道病毒蛋白。在本发明另一实施方案中，病毒蛋白是流感病毒蛋白。

本发明另一方面是包括第一siRNA和第二siRNA的组合物，第一siRNA和第二siRNA各自减少编码病毒蛋白的基因表达。在本发明一实施方案中，第一siRNA减少编码第一病毒蛋白的第一基因的表达，第二siRNA减少编码第二病毒蛋白的第二基因的表达。在本发明的相关实施方案中，第一siRNA和第二siRNA减少所述第一基因和第二基因表达的至少约25％。在本发明另一实施方案中，第一基因和第二基因来自同一病毒种的两种毒株。在本发明另一相关实施方案中，第一基因和第二基因来自同一病毒属的两个物种。在本发明另一相关实施方案中，第一基因和第二基因来自同一病毒科的两种病毒。在本发明另一实施方案中，该组合物进一步包括减少编码第三病毒蛋白的第三基因表达至少约25％的第三siRNA。在相关实施方案中，该组合物还包括阳离子聚合物。

本发明的另一方面是诊断试剂盒，其包括针对至少部分的病毒蛋白基因检测所述基因的引物或探针，其中所述部分是保守位点。

本发明的另一方面是减少靶病毒基因在病毒感染哺乳动物细胞中表达的方法，包括以下步骤：将所述细胞与减少病毒蛋白基因表达的siRNA接触，以使所述siRNA进入所述哺乳动物细胞的细胞质并减少所述病毒蛋白基因至少约25％的表达。在本发明一实施方案中，病毒蛋白获自选自人类呼吸道合胞病毒、人类偏肺病毒、1型人类副流感病毒、2型人类副流感病毒、3型人类副流感病毒、4a型人类副流感病毒、4b型人类副流感病毒、鼻病毒和流感病毒的病毒。在本发明另一实施方案中，病毒蛋白基因是呼吸道病毒蛋白基因。在本发明另一实施方案中，病毒蛋白基因是流感病毒蛋白基因。

本发明另一方面是递送siRNA至需要其的患者的方法，包括将包括有效量的siRNA的组合物给药于所述患者，其中所述siRNA减少病毒蛋白基因至少约25％的表达。在本发明一实施方案中，siRNA以患者体重的约0.1mg/kg至约20mg/kg的浓度递送给患者。在本发明另一实施方案中，siRNA以患者体重的约0.1mg/kg至约10mg/kg的浓度递送给患者。在本发明另一实施方案中，siRNA以患者体重的约0.1mg/kg至约50mg/kg的浓度递送给患者。在本发明另一实施方案中，siRNA减少病毒蛋白基因至少约25％的表达。在本发明另一实施方案中，siRNA包括表1-9所列的核酸序列。在本发明另一实施方案中，该组合物还包括阳离子聚合物。在本发明另一实施方案中，该组合物以吸入、鼻内、口服或静脉内给药。

本发明的另一方面是防止或治疗患者病毒感染的方法，包括将包含靶向病毒蛋白基因的siRNA或shRNA的治疗化合物给药于患者。在本发明一实施方案中，所述siRNA或shRNA长度在约15和约60个核苷酸之间，并包括：至少约85％相同于编码病毒蛋白的核酸的一部分的第一核酸序列；和至少85％互补于所述第一核酸部分的第二核酸序列。在本发明另一实施方案中，siRNA是双链siRNA分子，其中所述siRNA分子的各链是约1 5至约50个核苷酸，其中所述siRNA分子的一条链包括与呼吸道病毒核酸序列内保守位点或其变体相同的核酸序列。在本发明另一实施方案中，呼吸道病毒选自人类呼吸道合胞病毒、人类偏肺病毒、1型人类副流感病毒、2型人类副流感病毒、3型人类副流感病毒、4a型人类副流感病毒、4b型人类副流感病毒、鼻病毒和流感病毒。在本发明另一实施方案中，核酸序列编码核蛋白基因。在本发明另一实施方案中，呼吸道病毒是流感病毒，其中siRNA不是选自SEQ ID NO.10710-10751。在本发明另一实施方案中，治疗化合物包括阳离子聚合物。

本发明的另一方面是siRNA用于制备抑制哺乳动物患者呼吸系统病毒繁殖的药剂的用途，包括向患者施用含有靶向于病毒蛋白质基因的siRNA或shRNA的治疗化合物。在本发明一个实施方案中，siRNA或shRNA长度在约15和约60个核苷酸之间，并包括：至少约85％相同于编码病毒蛋白的核酸的一部分的第一核酸序列；和至少85％互补于所述第一核酸部分的第二核酸序列。在本发明另一实施方案中，siRNA是双链siRNA分子，其中所述siRNA分子的各链是约15至约50个核苷酸，其中所述siRNA分子的一条链包括与呼吸道病毒核酸序列内保守位点或其变体相同的核酸序列。在本发明另一实施方案中，呼吸道病毒选自人类呼吸道合胞病毒、人类偏肺病毒、1型人类副流感病毒、2型人类副流感病毒、3型人类副流感病毒、4a型人类副流感病毒、4b型人类副流感病毒、鼻病毒和流感病毒。在本发明另一实施方案中，核酸序列编码蛋白(NP)基因。在本发明另一实施方案中，呼吸道病毒是流感病毒，其中siRNA不是选自SEQ IDNO.10710-10751。在本发明另一实施方案中，呼吸道病毒是流感病毒，其中siRNA选自SEQ ID NO.1-10709。

本发明的另一方面是鉴别存在于两种或多种病毒的病毒蛋白转录子中的siRNA或shRNA靶序列的方法，包括以下步骤：a)提供编码来自病毒的病毒蛋白的核酸序列；b)鉴别所述核酸序列的靶部分，其中所述部分包括约19个核苷酸且不包括多于3个连续鸟嘌呤核苷酸或多于3个连续胞嘧啶核苷酸；和c)重复步骤a和b一次或多次，每次重复使用不同病毒，从而鉴别病毒蛋白转录子中的siRNA或shRNA靶序列。在本发明一个实施方案中，所述核酸序列包括蛋白序列的保守位点。在本发明另一实施方案中，该方法进一步包括产生结合于所述靶序列的siRNA或shRNA。

本发明的另一方面是一种诊断病毒感染的方法，包括确定患者是否感染了对诱导RNAi的实体抑制敏感的病毒。在本发明一实施方案中，该方法进一步包括将诱导RNAi的实体给药于患者的步骤。

本发明的另一方面是治疗或防止流感病毒感染的方法，包括将诱导RNAi的实体给药于需要的患者。

本发明的另一方面是抑制呼吸道病毒繁殖的双链siRNA分子，其中所述siRNA分子的各链是约15至约50个核苷酸，其中所述siRNA分子的一条链包括与呼吸道病毒核酸序列内保守位点或其变体相同的核酸序列。在本发明另一实施方案中，呼吸道病毒选自人类呼吸道合胞病毒、人类偏肺病毒、1型人类副流感病毒、2型人类副流感病毒、3型人类副流感病毒、4a型人类副流感病毒、4b型人类副流感病毒、鼻病毒和流感病毒。在相关方案中，核酸序列编码蛋白(NP)基因。在本发明另一实施方案中，呼吸道病毒是流感病毒，其中siRNA不是选自SEQ ID NO.10710-10751。在本发明另一实施方案中，呼吸道病毒是流感病毒，其中siRNA选自SEQ ID NO.1-10709。

附图说明

图1.A-K展示了本发明靶病毒的系列核酸序列比对。图1A分别以表观顺序公开了SEQ ID NO 11,246-11,430。图1B分别以表观顺序公开了SEQID NO 11,431-11,434。图1C分别以表观顺序公开了SEQ ID NO11,435-11,440。图1D分别以表观顺序公开了SEQ ID NO 11,441-11,443。图1E分别以表观顺序公开了SEQ ID NO 11,444-11,446。图1F分别以表观顺序公开了SEQ ID NO 11,447-11,450。图1G分别以表观顺序公开了SEQID NO 11，451-11,454。图1H分别以表观顺序公开了SEQ ID NO11,455-11,458。图1I分别以表观顺序公开了SEQ ID NO 11,459-11,461。图1J分别以表观顺序公开了SEQ ID NO 11,462-11,465。图1K分别以表观顺序公开了SEQ ID NO 11,466-11,470。

图2.通过给药流感特异性siRNA抑制小鼠中流感病毒繁殖。对小鼠静脉注射增加量的与jetPEI复合的NP-1496 siRNA或GFP siRNA。3小时后，用甲型流感的PR8变种感染小鼠。感染后24小时使用MDCK-HA检测中的肺匀浆测量病毒滴度。每个数据点代表1只小鼠。各组间的P值表示统计显著性。

图3.治疗性给药siRNA抑制小鼠流感病毒产生。流感感染后5小时，对小鼠注射混有jetPEI的NP-siRNA或PA siRNA。感染后28小时使用MDCK-HA检测中的肺匀浆测量病毒滴度。每个数据点代表1只小鼠。各组间的P值表示统计显著性。

图4.流感特异性siRNA处理提供了宽泛的抗高度致病性H5和H7甲型禽流感病毒的致死攻击的交叉保护。在病毒攻击之前1天，对BALB/c小鼠(每组8个)静脉给与50μgsiRNA，在病毒攻击的当天静脉给与20μgsiRNA。10 LD50剂量的鼻内病毒攻击后，对小鼠的体重和存活率监测16天。填充圆圈，GFP-特异性siRNA；空白圆圈，NP+PA-特异性siRNA。指出了P值。

图5.以指定量的NP特异性siRNA的PBS溶液或PBS对照鼻内处理BALB/c小鼠。2小时后，以PR8血清型鼻内感染所有小鼠(1000 pfu/小鼠)。感染后24小时收集肺，以MDCK-HA检测从肺匀浆测量病毒滴度。PBS和siRNA组之间的P值表示0.5、1和2 mg/kg siRNA处理组的统计显著性。

图6.对BALB/c小鼠鼻内给药对照和NP-靶向siRNA(10 mg/kg，PBS中)。3小时后对所有小鼠鼻内(i.n.)感染PR8病毒(50 pfu/小鼠)。感染后24小时和48小时收集肺，从左肺分离总RNA。使用dT18引物将总RNA反转录为cDNA。使用PB1特异性引物进行实时PCR以定量病毒mRNA水平。GAPDH用作中间对照。将右肺和左肺均质化，以MDCK-HA检测测量病毒滴度。感染48小时后的样品中的病毒滴度示于图中(使用student检验发现PBS和NP siRNA处理组之间存在统计显著性(p＝0.01))；感染24小时后的样品中的滴度太低而检测不到，可能是因为siRNA引导的抑制。

图7.以10 mg/kg的亲环蛋白B特异性siRNA或GFP siRNA的PBS溶液或PBS对照鼻内处理BALB/c小鼠。每组有5只小鼠。24小时后收集小鼠的肺。从肺样品纯化总RNA，使用dT18引物进行反转录。实时PCR中使用亲环蛋白B特异性引物以定量靶mRNA水平。GAPDH特异性引物也在PCR反应中用作对照。

图8.显示了蜗状siRNA制品鼻内给药体内抑制流感病毒。

图9.显示了蜗状siRNA制品静脉内给药体内抑制流感病毒。

图10A.用于流感病毒抑制的以蜗状制品递送的siRNA静脉内给药的剂量-反应图。

图10B.显示了蜗状siRNA制品口服强饲给药体内抑制流感病毒。

图11A-C.实验的结果显示siRNA抑制MDCK细胞中流感病毒繁殖。通过电穿孔法将靶向不同病毒转录子的6种不同siRNA引入MDCK细胞，8小时后以病毒感染细胞。图11A是显示在感染后各时间血凝素检测培养物上清液中病毒滴度的时间过程，该感染是以病毒毒株A/PR/8/34(H1N1)(PR8)，存在或不存在各siRNA或对照siRNA情况下以0.01的感染复数(MOI)。图11B是显示在感染后各时间血凝素检测培养物上清液中病毒滴度的时间过程，该感染是以流感病毒毒株A/WSN/33(H1N1)(WSN)，存在或不存在各siRNA或对照siRNA情况下以0.01的MOI。图11C是病毒感染细胞中培养物上清液中病毒滴度的噬菌斑测定，该细胞模拟转染或以siRNA NP-1496转染。图11D显示在不同剂量siRNA抑制流感病毒繁殖。以指示量的NP-1496 siRNA转染MDCK细胞，然后以PR8病毒以0.01的MOI感染。感染后48小时测量病毒滴度。显示了两次实验中的一次的代表性数据。

图12.显示了与抑制流感病毒效力有关的各siRNA相对于流感病毒基因片段的位置。

图13A.显示了培育鸡胚的示意图，指出了注射siRNA和siRNA/递送剂组合物的区域。

图13B.显示了各siRNA在培育鸡胚中抑制流感病毒繁殖的能力。

图14.显示了核蛋白与病毒RNA分子相互作用的示意图。

图15.显示了流感病毒vRNA、mRNA和cRNA(模板RNA)之间的差异和相互关系的示意图。

图16.显示了在感染前6-8小时经模拟转染或以siRNA NP 1496转染的细胞中，在病毒感染后各时间病毒NP和NS RNA的量。公布的序列为SEQ ID NO：11,492。

图17A和17B.图17A显示抑制流感病毒繁殖需要双链体siRNA中的野生型(wt)反义链。MDCK细胞首先以wt和修饰的(m)链形成的siRNA转染，8小时后以PR8病毒以0.1的MOI感染。感染24小时后检测培养物上清液中的病毒滴度。显示了两个实验之一的代表数据。图17B显示M-特异性siRNA抑制特异性mRNA的蓄积。M-37转染MDCK细胞，以PR8病毒以0.01的MOI感染，感染1、2和3小时后收集以分离RNA。使用RNA-特异性引物反转录，之后实时PCR来测量M-特异性mRNA、cRNA、和vRNA的水平。各种病毒RNA的水平标准化到同一样品中γ-肌动蛋白mRNA(底板)的水平。各RNA的相对水平显示为平均值+-.S.D。显示了两个实验之一的代表数据。

图18A-D.显示NP-特异性的siRNA不仅抑制Np-特异性mRNA、vRNA、和cRNA的蓄积，还抑制M-特异性和NS-特异性mRNA、vRNA、和cRNA的蓄积。以NP-1496转染MDCK(A-C)和Vero(D)细胞，以PR8病毒以0.1的MOI感染，感染1、2和3小时后收集MDCK(A-C)和Vero(D)细胞以分离RNA。使用RNA-特异性引物反转录，之后实时PCR来测量NP-特异性、M-特异性和NS-特异性mRNA、cRNA、和vRNA的水平。各种病毒RNA的水平标准化到同一样品中γ-肌动蛋白mRNA(未显示)的水平。显示各RNA的相对水平。显示了两个实验之一的代表数据。

图18E-G.各图的右侧显示PA-特异性siRNA不仅抑制PA-特异性mRNA、vRNA、和cRNA的蓄积，还抑制M-特异性和NS-特异性mRNA、vRNA、和cRNA的蓄积。以PA-1496转染MDCK细胞，以PR8病毒以0.1的MOI感染，感染1、2和3小时后收集MDCK细胞以分离RNA。使用RNA-特异性引物反转录，之后实时PCR来测量PA-特异性、M-特异性和NS-特异性mRNA、cRNA、和vRNA的水平。各种病毒RNA的水平标准化到同一样品中γ-肌动蛋白mRNA(未显示)的水平。显示各RNA的相对水平。

图18H.图18H显示NP-特异性siRNA抑制PB1-特异性mRNA(上板)、PB2-特异性mRNA(中板)和PA-特异性mRNA(下板)的蓄积。以NP-1496转染MDCK细胞，以PR8病毒以0.1的MOI感染，感染1、2和3小时后收集MDCK细胞以分离RNA。使用RNA-特异性引物反转录，之后实时PCR来测量PB1-特异性、PB2-特异性和PA-特异性mRNA的水平。各种病毒RNA的水平标准化到同一样品中γ-肌动蛋白mRNA(未显示)的水平。显示各RNA的相对水平。

图19A-C.图19A是显示流感病毒感染前与阳离子聚合物PEI一起给药siRNA抑制小鼠流感病毒繁殖的图。填充方块(未处理)；空白方块(GFPsiRNA)；空白圆圈(30.mu.g NP siRNA)；填充圆圈(60.mu.g NP siRNA)。每个符号代表1只动物。显示了各组之间的p值。图19B是显示流感病毒感染前与阳离子聚合物PLL一起给药siRNA抑制小鼠流感病毒繁殖的图。填充方块(未处理)；空白方块(GFP siRNA)；填充圆圈(60.mu.g NPsiRNA)。每个符号代表1只动物。显示了各组之间的p值。图19C是显示流感病毒感染前与阳离子聚合物jetPEI一起给药siRNA抑制小鼠流感病毒繁殖比以PBS给药显著有效的图。空白方块(未处理)；空白三角(PBS中的GFP siRNA)；填充三角(PBS中的NP siRNA)；空白圆圈(伴有jetPEI的GFP siRNA)；填充圆圈(伴有jetPEI的NP siRNA)。每个符号代表1只动物。显示了各组之间的p值。

图20.显示流感病毒感染前同时给药靶向流感病毒NP和PA转录子的siRNA显示出累积效应的图。填充方块(未处理)；空白圆圈(60.mu.g NPsiRNA)；空白三角(60.mu.g PA siRNA)；填充圆圈(60.mu.g NP siRNA+60.mu.g PA siRNA)。每个符号代表1只动物。显示了各组之间的p值。

图21.显示流感病毒感染后给药siRNA抑制小鼠流感病毒繁殖的图。填充方块(未处理)；空白方块(60.mu.g GFP siRNA)；空白三角(60.mu.gPA siRNA)；空白圆圈(60.mu.g NP siRNA)；填充圆圈(60.mu.g NPsiRNA+60.mu.g PA siRNA)。每个符号代表1只动物。显示了各组之间的p值。

图22A-C.图22A是表达shRNA的慢病毒载体的结构图。shRNA的转录由U6启动子驱动。EGFP表达由CMV启动子驱动。SIN-LTR、.PSI.、cPPT和WRE是慢病毒元件。显示了NP-1496 shRNA的序列。图22B表示流式细胞术结果，证实图22B所示慢病毒感染的Vero细胞以剂量依赖的方式表达EGFP。通过将编码NP-1496a shRNA的DNA载体与封装载体共转染入293T细胞而繁殖慢病毒。培养物上清液(0.25ml或1.0m1)用于感染Vero细胞。所得到的Vero细胞系(Vero-NP-0.25和Vero-NP-1.0)和对照(未感染的)Vero细胞由流式细胞术分析GFP表达。显示了Vero-NP-0.25(图的上部)和Vero-NP-1.0(图的下部)细胞的平均荧光强度。阴影曲线代表对照(未感染的)Vero细胞的平均荧光强度。图22C显示在表达NP-1496 shRNA的Vero细胞中流感病毒繁殖的抑制。亲本Vero细胞和表达NP-1496 shRNA的Vero以PR8病毒以0.04、0.2和1的MOI感染。上清液中的病毒滴度通过感染后48小时血凝素(HA)检测而确定。

图23.显示表达靶向于流感病毒转录子的siRNA的DNA载体的给药抑制小鼠流感病毒繁殖。编码RSV、NP-1496(NP)或PB1-2257(PB1)shRNA的60.mu.g DNA与40.mu.1 Infasurf混合并通过滴注给药于小鼠。对无处理(NT)组小鼠滴注60.mu.15％葡萄糖。13小时后，以PR8病毒每小鼠12000pfu鼻内感染小鼠。感染后24小时以MDCK/血凝素检测测量肺中的病毒滴度。每个数据点代表1只小鼠。显示了各组之间的p值。

发明详述

本发明是基于胞内RNA干扰(RNAi)的现象。细胞内含有互补于靶RNA的部分的双链RNA的存在以序列特异性的方式抑制了靶RNA的表达。通常，抑制是由于裂解靶或抑制其翻译而造成的。RNAi是对诸如病原体感染等刺激的正常细胞反应，也是使受到这样的感染所扰乱的系统恢复平衡的有效机制。而且，RNAi可用于特异性地破坏胞内信号传导途径。

驱动RNAi活性的双链RNA结构是siRNA、shRNA和其它能被处理以严生siRNA或shRNA的双链结构(dsRNA)(或能通过RNA干扰抑制靶转录子表达的任何其它小RNA种类)。诱导RNAi的实体如siRNA和shRNA可引入患者或其离体细胞，并调节特异性信号转导途径。而且，这些dsRNA对于特征为异常细胞信号转导的疾病或疾患是有效的防止和治疗药物。例如，感染哺乳动物的病毒通过控制宿主细胞的细胞机器而复制。因此使用RNAi技术来破坏控制病毒繁殖的病毒信号转导途径是有效的。

已知某些病毒基因控制病毒生命周期两个阶段中的关键。本领域现有的工作集中于病毒聚合酶是siRNA的有效靶，因为它们对病毒复制是需要的。例如，RNA依赖性RNA聚合酶(RdRP)在转录和复制中都是必要的多肽。这导致如下推测：RdRP亚基的沉默将导致几乎所有RNA合成的丧失，并因此导致病毒繁殖的显著抑制。事实上，该结果已经在RSV、水泡性口炎和副流感病毒中观察到。(见，Barik S.Control of nonsegmentednegative-strand RNA virus replication by siRNA(siRNA对非片段的负链RNA病毒复制的控制).Virus Res.2004 Jun 1；102(1)：27-35；和Bitko等，Phenotypic silencing of cytoplasmic genes using sequence-specificdouble-stranded short interfering RNA and its application in the reversegenetics of wild type negative-strand RNA viruses(使用序列特异性双链短干扰RNA的细胞质基因表型沉默及其在野生型负链RNA病毒的反求遗传学中的应用).BMC Microbio1.2001；1(1)：34.Epub 2001 Dec 20.)。发现另一种病毒蛋白(不同地称为核蛋白、衣壳或核衣壳)参与例如病毒转录和复制。然而，对核蛋白进行的反义研究没有指出编码此多肽的转录子是象聚合酶那么合适的靶。(见，Hatta等.Inhibition of influenza virus RNA polymerase and nucleoprotein genes expression by unmodified，phosphorothioated，and liposomally encapsulated oligonucleotides(未修饰的磷硫酰化的脂质体包被的寡核苷酸对流感病毒RNA聚合物及核蛋白基因表达的抑制).Biochem Biophys Res Commun.1996 Jun 14；223(2)：341-6；和Mizuta等.Antisense oligonucleotides directed against the viral RNApolymerase gene enhance survival of mice infected with influenza A(定向抗病毒RNA聚合酶基因的反义寡核苷酸提高了感染甲型流感病毒的小鼠的存活).Nat Biotechnol.1999 Jun；17(6)：583-7.)。近来siRNA的研究已表示考察核蛋白作为siRNA可能的靶。Gitlin等.Short interfering RNA confersintracellular antiviral immunity in human cells(短干扰RNA赋予人类细胞中的细胞内抗病毒免疫).Nature.2002 Jul 25；418(6896)：430-4；Fowler等.Inhibition of Marburg virus protein expression and viral release by RNAinterference(RNA干扰对马尔堡病毒蛋白表达和病毒释放的抑制).J GenVirol.2005 Apr；86(Pt 4)：118 1-8；和Yuan等.Inhibition of coxsackievirus B3replication by small interfering RNAs requires perfect sequence match in thecentral region of the viral positive strand(小干扰RNA对科萨奇病毒B3复制的抑制需要病毒正链中心区域中的完美序列匹配).J Virol.2005 Feb；79(4)：2151-9。本发明证明使用针对病毒核蛋白序列的siRNA来破坏病毒信号转导途径并抑制病毒复制。进一步地，本发明的发明人确定另一种病毒蛋白、核蛋白或核衣壳蛋白的抑制或沉默与抑制聚合酶活性有类似的效应。因此，核蛋白转录子是对siRNA的优选靶。

不希望受任何理论束缚，NP siRNA的宽效应可能是NP结合并稳定vRNA和cRNA的重要性的结果，而不是NP-特异性siRNA非特异性靶向RNA降解。例如，流感病毒中的NP基因片段编码单链RNA结合核蛋白，单链RNA结合核蛋白可结合vRNA和cRNA。在病毒生命周期中，首先转录和翻译NP mRNA。NP蛋白的主要功能是衣壳化病毒基因组用于RNA转录、复制和封装。没有NP蛋白时，vRNA和cRNA的全长合成都严重受损。当NP siRNA诱导NP RNA降解时，NP蛋白合成受损，导致缺少有效NP蛋白，随后影响其它病毒基因片段的复制。以这种方式，NP siRNA能在较早期有效抑制病毒繁殖。因此，病毒核蛋白的多功能特征使其成为基于RNAi治疗的有效靶，提供了由抑制单个基因而在病毒生命周期多个不同阶段干涉的机会。

已经假设受感染宿主细胞中NP蛋白分子的数目调节mRNA合成，相对于基因组RNA(vRNA和cRNA)的复制。使用NP蛋白中温度敏感的突变，此前的研究已经显示cRNA而不是mRNA的合成在体外和体内是温度敏感的。已经显示NP蛋白对于新生cRNA和vRNA转录子的延伸和抗终止是需要的。此处列出的结果证明病毒NP-特异性siRNA抑制受感染细胞中所有病毒RNA的蓄积。尽管不希望受束缚于任何理论，但很可能在NP-特异性siRNA存在下，新转录的NP mRNA被降解，导致在病毒感染后抑制NP蛋白合成。没有新合成的NP，从而抑制进一步的病毒转录和复制以及新病毒粒子的产生。

参考附图，本发明的特征和其它细节将更具体地描述，并在权利要求中指出。应该理解的是，此处所述的特定实施方案是以示例的方式而不是本发明的限制。本发明的主要特征可以各种实施方案采用而不偏离本发明范围。除非另外具体说明，所有部分和百分比都是以重量计。

定义

为了方便，用于说明书、实施例和附带权利要求的一些术语集中于此。除非另外定义，此处所用的所有技术和科学术语具有如本发明所属领域普通技术人员通常理解的含义。然而，对于这些定义在本领域内有不同含义的情况，以下定义用于控制。

“核苷酸”包括含氮碱基、糖分子、和磷酸基。“核苷”包括连接于糖分子的含氮碱基(核碱基(nucleobase))。在天然产生的核酸中，磷酸基共价连接相邻的核苷以形成聚合物。核酸可包括天然形成的核苷(如腺苷、胸苷、鸟苷、胞苷、尿苷、脱氧腺苷、脱氧胸苷、脱氧鸟苷、和脱氧胞苷)、核苷类似物(如2-氨基腺苷、2-硫代胸苷、肌苷、吡咯并嘧啶、3-甲基腺苷、C5-丙炔基胞苷、C5-丙炔基尿苷、C5-溴尿苷、C5-氟尿苷、C5-碘尿苷、C5-甲基胞苷、7-去氮腺苷、7-去氮鸟苷、8-氧代腺苷、8-氧代鸟苷、O(6)-甲基鸟嘌呤、和2-硫代胞苷)、化学改性的碱基、生物修饰的碱基(如甲基化碱基)、嵌入碱基、改性的糖(如2’-氟核糖、核糖、2’-脱氧核糖、阿拉伯糖、和己糖)。

术语“RNA”或“RNA分子”或“核糖核酸分子”指核糖核苷酸的聚合物。术语“DNA”或“DNA分子”或“脱氧核糖核酸分子”指脱氧核糖核苷酸的聚合物。DNA和RNA可为天然合成的(如分别通过DNA复制或DNA或RNA的转录)。RNA可为转录后修饰的。DNA和RNA还可为化学合成的。术语“靶mRNA”和“靶转录子”此处同义地使用。

术语“RNA干扰(interference)”(“RNAi”)指RNA的选择性胞内降解(也指基因沉默)。RNAi还包括微RNA或作用象微RNA的siRNA的翻译抑制。RNAi可以通过引入小干扰RNA(siRNA)或胞内产生siRNA(如从质粒或转基因)而起始，以沉默一个或多个目标基因的表达。或者，RNAi在细胞中天然发生以除去外来RNA(如病毒RNA)。天然RNAi通过Dicer引导的前体dsRNA断裂而继续进行，这将降解机制引导至其它关联的RNA序列。

术语“小干扰RNA”(“siRNA”)，本领域中也指“短干扰RNA”，指包括约10-60个核苷酸(或核苷酸类似物)，能够指引或介导RNA干扰的RNA(或RNA类似物)。术语“siRNA”包括双链siRNA和单链siRNA。一般此处所用的术语“siRNA”指双链siRNA(与单链或反义RNA相比)。术语“短发夹RNA”(“shRNA”)是指折叠成发夹结构并含有至少一个核苷酸的单链部分(“环”)的siRNA(或siRNA类似物)前体，如，含有至少两个互补部分和至少一个单链部分的RNA分子，该至少两个互补部分杂交或能够杂交以形成足够长以介导RNAi(如所述用于siRNA双链体的)的双链(双链体)结构，该至少一个单链部分通常长约1至10个核苷酸以形成连接shRNA区域的环从而形成双链体部分。该双链体部分可能，但通常不会，在一条链或两条链含有一个或多个错配和/或一个或多个由一个或多个未配对的核苷酸组成的凸起。不希望被理论束缚，认为shRNA由保守胞内RNAi机制加工为siRNA。shRNA能抑制与shRNA一部分(指shRNA反义链或引导链)互补的靶转录子的表达。通常，shRNA引导链与靶转录子之间形成的双链体的特征类似于siRNA与靶转录子之间形成的双链体。在本发明的一些实施方案中，shRNA的5’末端具有磷酸基而另一些实施方案中不具有。在本发明的一些实施方案中，shRNA的3’末端具有羟基。

术语“诱导RNAi的实体”或“RNAi剂”指一种RNA(不同于非人工修饰或人工传送至其位置的天然产生的分子)，其在细胞中的存在导致RNAi并导致RNAi剂所靶向的RNA表达减少。RNAi剂可为siRNA或shRNA。在本发明一些实施方案中，siRNA可含有通过内源小RNA(指微RNA)采用的翻译阻遏途径抑制靶RNA表达的链。在本发明一些实施方案中，shRNA可胞内加工以产生一种经由此微RNA翻译阻遏途径抑制靶RNA表达的siRNA。任何“靶RNA”可指“靶转录子”，而不考虑靶RNA是否为信使RNA。术语“靶RNA”与“靶转录子”在此互换地使用。RNAi诱导剂包括RNAi剂和载体(不同于上述未经人工修饰的天然产生的分子)，其在细胞中的存在导致RNAi并导致RNAi剂所靶向的RNA表达减少。

“RNAi诱导载体”包括一种载体，其在细胞中的存在导致一种或多种RNA转录，所述RNA自身杂交或互相杂交以形成RNAi剂。在本发明各实施方案中，该术语包括质粒，如DNA载体(其序列可包括衍生自病毒的序列元件)，或病毒(不同于非经由人工修饰的天然产生的病毒或质粒)，其在细胞中的存在导致一种或多种RNA转录，所述RNA自身杂交或互相杂交以形成RNAi剂。通常，载体包括可操作连接于表达信号的核酸，从而当载体存在于细胞中时，杂交或自身杂交以形成RNAi剂的一种或多种RNA分子被转录。因此载体提供了用于胞内合成RNAi剂的模板。为了诱导RNAi，病毒基因组存在于细胞(如在病毒衣壳与细胞膜融合之后)认为足以构成病毒存在于细胞内。此外，为了诱导RNAi，如果载体被引入细胞、进入细胞、或继承自母体细胞，都认为载体存在于细胞，而不考虑它随后在细胞中是否被修饰或加工。如果载体在细胞中的存在导致一种或多种RNA产生，所述RNA互相杂交或自身杂交以形成靶向于转录子的RNAi剂，即，如果载体在细胞中的存在导致一种或多种靶向于转录子的RNAi产生，则RNAi诱导载体被认为是靶向于转录子。术语“诱导”的使用不是指RNAi剂必须活化或上调RNAi，仅仅指载体在细胞中的存在导致RNAi剂在细胞中产生，导致RNAi介导的该剂所靶向的RNA表达减少。

RNAi诱导实体被认为是靶向靶转录子，目的如此处所述，如果(1)该剂包含一条链，其在长15-29个核苷酸的评价窗口大致互补于靶转录子，如15，更优选至少约17，更优选在长至少约18或19至约21-23或24-29个核苷酸的评价窗口。例如在本发明各实施方案中该剂包括一条链，其在长15-29个核苷酸的评价窗口具有互补于靶转录子的至少约70％，优选至少约80％、84％、89％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、或100％精确序列，如15，更优选至少约17，更优选在长至少约18或19至约21-23或24-29个核苷酸的评价窗口；或(2)RNAi剂的一条链在严格条件下杂交于靶转录子，用于在体外和/或哺乳动物细胞质或细胞核中常见条件下杂交小(＜50核苷酸)RNA分子。此外，在剂通过微RNA翻译阻遏途径起作用的情况，该剂和靶形成的双链体含有至少一个凸起和/或错配。在本发明一些实施方案中，引导链和靶转录子形成的双链体中的GU或UG碱基对不认为是错配，为了确定RNAi剂是否靶向于转录子。

在细胞中的存在导致产生靶向于转录子的RNAi剂的RNA诱导载体也认为是靶向于转录子。因为靶向转录子的效应是减少或抑制引导转录子合成的基因的表达，靶向转录子的RNAi剂也认为是靶向引导转录子合成的基因，即使基因本身(如在细胞的情况为基因组DNA)不认为与该剂或胞内沉默机器相互作用。因此靶向转录子的RNAi剂或载体理解为靶向为转录子合成提供模板的基因。

病毒“核蛋白”(也称“衣壳蛋白”或“核衣壳蛋白”)是一种病毒多肽，其隔离病毒RNA并影响病毒转录。病毒核蛋白能够形成核酸/蛋白复合体(即核糖核蛋白(RNP)复合体)。双链病毒中核蛋白也称为“NS”(如NS-6)。核蛋白不同于外部衣壳蛋白，后者通常不接触和隔离病毒基因组。术语“核蛋白mRNA”、“NP mRNA”、“核蛋白转录子”、和“NP转录子”理解为包括编码病毒核蛋白或如此处所述其功能等价物的任何mRNA。

本领域普通技术人员应理解，实现病毒核蛋白一种或多种功能的蛋白具有大量不同名称，取决于感兴趣的特定病毒。例如，在某些病毒如流感的情况该病毒称为核蛋白(NP)，而在大量其他单链RNA病毒的情况，实现类似功能的蛋白质称为核衣壳(NC或N)蛋白。在另一些病毒中，既接触基因组核酸又在病毒颗粒中起结构作用的类似蛋白称为衣壳(C)蛋白。

术语“核蛋白mRNA”、“NP mRNA”、“核蛋白转录子”、和“NP转录子”理解为包括编码病毒核蛋白或如此处所述其功能等价物的任何mRNA。含有核蛋白基因或其功能等价物的任何病毒适合作为siRNA靶。通过非限制性示例的方式，靶病毒的若干组在此详细描述。

“患者”包括活着的生物，如人类、猴、奶牛、绵羊、马、猪、牛、山羊、狗、猫、小鼠、大鼠、从其培养的细胞、和转基因种。在优选实施方案中，患者是人。患者与“病人”同义。将本发明组合物给药于待处理的患者可通过已知途径、以至少有效治疗该患者的疾病的剂量和时段进行。达到治疗效果必需的有效量化合物可根据多种因素而不同，如患者年龄、性别、体重，以及治疗化合物处理患者外来物质的能力。可调整给药方案以提供最优的治疗反应。例如，可每天给药多个单独剂量，或者该剂量可根据治疗情况的要求所示成比例地减少。

如此处所用，用于数字的术语“大约”或“约”是通常取值包括落入该数字在任一方向(大于或小于该数字)5％范围内的数字，除非另外指明或从上下文明显看出(除了这种数字将超过可能值的100％)另外的说明。指明范围时，其端值包括在范围内，除非另外指明或从上下文明显看出另外的说明。

术语“互补”此处所用是根据本领域接受的含义，指特定碱基、核苷、核苷酸或核酸之间精确配对的能力。例如，腺嘌呤(A)和尿嘧啶(U)互补；(A)与胞嘧啶(T)互补；鸟嘌呤(G)和胸腺嘧啶(C)互补，在本领域中称为沃森-克里克碱基配对。如果第一核酸序列某位置的核苷酸与第二核酸序列相对位置的核苷酸互补，这些核苷酸形成互补碱基对，核酸在此位置互补。本领域普通技术人员应理解，核酸是以反向平行的方向排列(即，一条核酸以5’至3’方向而另一条是3’至5’方向)。两条核酸或其部分的互补程度可通过当两条核酸或其部分以反向平行的方向排列以最大化互补时，在一个评价窗上确定两条链中形成互补碱基对的核苷酸总数与核苷酸总数的百分比而评价。例如，AAAAAAAA(SEQ ID NO：11424)与TTTGTTAT(SEQID NO：11424)75％互补，因为互补碱基对中有12个核苷酸，而总共有16个。在一个评价窗上至少70％互补的核酸认为大致互补。具体地，如果评价窗长15-16个核苷酸，大致互补的核酸可在该窗内具有0-3个错配；如果评价窗长17个核苷酸，大致互补的核酸可在该窗内具有0-4个错配；如果评价窗长18个核苷酸，大致互补的核酸可在该窗内具有0-5个错配；如果评价窗长19个核苷酸，大致互补的核酸可在该窗内具有0-6个错配。在一些实施方案中，错配不是在连续的位置。在一些实施方案中，该窗含有长度不超过2个核苷酸的错配延展。在优选实施方案中，15-19个核苷酸的评价窗含有0-1个错配(优选0)，20-29个核苷酸的评价窗含有0-2个错配(优选0-1，更优选0)。

“大致纯”包括已经从天然伴随其成分分离的化合物(如药物、蛋白质或多肽)。通常，当样品中总物质的(体积比、湿重或干重比、摩尔比或摩尔分数)至少10％是感兴趣化合物时，化合物是大致纯的，更优选至少20％，更优选至少50％，更优选至少60％，更优选至少75％，更优选至少90％，更优选至少99％。可通过任何合适方法测量纯度，例如在多肽的情况下通过柱色谱、凝胶电泳或HPLC分析。当化合物如蛋白质实质上不含有天然伴随的成分或当其从天然状态下伴随的天然污染物中分离时，该化合物也是大致纯的。均匀地纯的化合物蛋白质或多肽也包括在术语“大致纯”的含义中，例如当样品中至少95％的总蛋白质(体积比、湿重或干重比、摩尔比或摩尔分数)是感兴趣的蛋白质或多肽时。

“给药”包括使得本发明的组合物执行其期望功能(如治疗或预防病毒疾病)的给药途径。大量给药途径都是可能的，根据待治疗的疾病或疾患包括但不限于，胃肠外(如静脉内、动脉内、肌肉内、皮下注射)、口服(如饮食地)、吸入(如至肺的气溶胶)、局部、鼻、直肠或经由缓释微载体。吸入和胃肠外给药是优选的给药方式。给药化合物的剂型将根据所选给药途径而改变(如溶液、乳剂、凝胶、气溶胶、胶囊)。包含待给药化合物的合适组合物可制备于生理可接受的媒介物或载体以及任选的佐剂和防腐剂。对于溶液或乳剂，合适的载体包括例如，水或醇/水溶液、乳剂或悬浮液，包括盐水和缓冲介质、无菌水、膏、软膏、洗剂、油、糊剂和固态载体。胃肠外媒介物可包括氯化钠溶液、Ringer’s葡萄糖、葡萄糖和氯化钠、乳酸化Ringer’s或不挥发性油。静脉内媒介物可包括各种添加剂、防腐剂、或液体、营养物或电解质补充物(见Remington’s PharmaceuticalScience，第16版，Mack，Ed.(1980))。

“有效量”包括允许本发明的组合物执行其期望功能如部分或完全地治疗或预防病毒感染等的量。有效量将取决于多种因素，包括生物活性、年龄、体重、性别、一般健康、待治疗疾病的严重度、以及合适的药物动力学特征。例如，活性物质的剂量可从约0.01 mg/kg/天至约100mg/kg/天，有利地从0.1mg/kg/天至约10mg/kg/天。例如，siRNA以从约0.1mg/kg/天至约5mg/kg/天的剂量递送给患者。活性物质的治疗有效量可以单剂量或多剂量从合适途径给药。而且，活性物质的剂量可如治疗或预防情况的需求而成比例地增加或减少。

“药学可接受的载体”包括与化合物活性相容且对患者来说生理上可接受的任何和所有溶剂、分散介质、包衣、抗菌剂和抗真菌剂、等渗剂和吸收延迟剂等。药学可接受的载体的例子包括缓冲的生理盐水(0.15MNaCl)。这种介质和剂用于药物活性物质的使用是本领域熟知的。除非与治疗化合物不相容，否则任何常规介质或剂用于适于药物给药的组合物的使用都包括在内。辅助活性化合物也可并入组合物。

“附加成分”包括但不限于以下的一种或多种：赋形剂；表面活性剂；分散剂；惰性稀释剂；粒化剂和崩解剂；结合剂；润滑剂；甜味剂；调味剂；着色剂；防腐剂；生理可降解的组合物如明胶；水性载体和溶剂；油性载体和溶剂；悬浮剂；分散或润湿剂；乳化剂、缓和剂；缓冲剂；盐；增稠剂；填充剂；乳化剂；抗氧化剂；抗生素；抗真菌剂；稳定剂；和药物上可接受的聚合或疏水物质。可包括在本发明药用组合物的其它“附加成分”是本领域已知的，描述于如Remington’s Pharmaceutical Science。

“保守位点”

病毒的保守位点是对于所给区域在所有已知序列的超过约70％中存在的位点或序列。通过以下方式确定具有与保守位点序列相同的siRNA组：从每个已知病毒序列衍生所有19-mer序列片段，并评价每个序列片段存在于每组病毒序列中作为正确配对的频率。第一病毒序列含有从位置1延展至19的19-mer序列片段，另一个从位置2至20，再一个从位置3至21，持续下去直到第19核苷酸位点位于链的末端。

以这样的方式提取第二、第三和第四病毒序列，直到列表中所列的最后一个病毒序列。随后把序列片段加至序列片段的增加的表中，保持含有各19-mer片段的病毒序列的数目的计数。片段频率以含有各特异性19-mer片段的病毒序列的百分比来表达。本发明的siRNA组是序列相同性大于大多数已知序列的，优选大于已知序列约70％的那些序列。

“流感病毒的保守位点”不包括2003年9月29日提交的美国专利申请第10/674,159号、公布号US-2004-0242518-A1(J.Chen，Q.Ge和M.Eisen，“InfluenzaTherapeutic”)和以下表清楚列出的(Seq.ID No 69-108)中公布的。

“保守位点的变体”包括小数目的错配，其在靶RNA和siRNA双链体的反义引导序列之间是容许的。因此，靶向病毒中高度保守位点的单siRNA双链体将通常对相对于保守位点仅具有1个或几个错配的小变体仍是活性的。我们在算法中使用了病毒错配数据以增加可能的甲型流感病毒序列变体的列表，该变体可由所给的siRNA双链体靶向，如以下实施例15所述。

核蛋白作为RNAi靶

本发明提供了使用RNAi以治疗或预防如人类和非人类哺乳动物等患者病毒复制或感染的组合物和方法。优选地，该病毒是RNA病毒。例如，RNA病毒是负链病毒。或者，病毒是正链病毒或双链(ds)病毒。优选的靶RNA是核蛋白(也称为核衣壳)转录子，或实现病毒核蛋白功能的病毒基因的转录子。含有核蛋白基因或其功能等价物的任何病毒适合作为siRNA靶。通过非限制性示例的方式，以下更详细地描述多组靶病毒。

负链RNA病毒

负链RNA病毒具有为mRNA互补有义的病毒基因组。因此，负链RNA病毒进入宿主细胞以后初始活性之一是转录和产生病毒mRNA。为了这个目的，病毒粒子携带N-RNA结构，该结构由紧密连接于病毒核蛋白(N或NP，有时称为核衣壳蛋白)的病毒RNA(vRNA)组成。依赖于RNA的RNA聚合酶或者直接结合于N-RNA(如在流感病毒的情况)，或者借助于辅助因子(如副粘病毒和杆状病毒的磷蛋白)的帮助而结合。完整的N-RNA而非无保护的vRNA是转录的实际模板，核蛋白促进N-RNA的核苷酸碱基暴露，用于有效地被合成酶通读。

表达和复制ssRNA(-)病毒的通用性显示为包括对RdRp的清楚的转录和复制，可能是由结合病毒粒子核蛋白(N或NP)亚基而激发。因此，RNA(-)和RNA(+)在复制复合体中可见与N蛋白复合。

用于本发明的负链RNA病毒包括人类呼吸道合胞病毒(RSV)、人类偏肺病毒(hMPV)、腮腺炎病毒、麻疹病毒、亨得拉病毒(Hendra virus)、新城疫病毒、流感病毒、疱疹性口炎病毒(VSV)、丁型肝炎病毒、马尔堡病毒、埃博拉病毒、汉坦病毒、辛诺柏病毒、拉沙热病毒、Lacrosse病毒、立夫特山谷热病毒、布尼亚病毒、白蛉热-西西里病毒、沙比亚病毒、瓜纳瑞托病毒、马丘坡病毒、胡宁病毒、淋巴细胞脉络丛脑膜炎病毒(LCMV)、和副流感病毒。其它合适的负链RNA病毒对本领域技术人员是已知的。示例病毒核蛋白核酸序列的Genbank登记号包括U41 071、NC_005077、K03362、NC_002045、NC_003443、NC_001781、AY297748、AF389119、AY705373、AY354458、NC_001608、AB027523和L37904。

流感

流感病毒是正粘病毒科的有包膜的负链RNA病毒。它们分为甲型流感、乙型流感和丙型流感，其中甲型流感是最有致病性的，认为是唯一能与动物种进行重排的类型。目前基于失活病毒的疫苗能在约70-80％的65岁以下健康个体中预防疾病；然而，这个比例在高龄或无免疫应答的个体中大大降低。此外，疫苗给药伴随的费用和可能的副作用使得该方法不是最优的。目前在美国批准了4种抗病毒药物以治疗和/或预防流感，即金刚烷胺、rimanadine、扎那米韦、奥塞米韦，但由于副作用、顺应性、和可能出现抗性株，它们的使用受到限制。因此，仍需要开发治疗和防止流感感染的有效药物。

流感核衣壳蛋白或核蛋白(NP)是与RNA片段相互作用以形成RNP的主要结构蛋白。它由甲型流感病毒的RNA片段5编码并长1,565核苷酸。NP含有498个氨基酸。NP蛋白在病毒复制中起重要作用。预测受感染细胞中NP蛋白分子的数量可调节mRNA合成相对于基因组RNA(vRNA和cRNA)复制的水平(1)。使用NP蛋白中温度敏感性突变，此前的研究表示cRNA而不是mRNA的合成在体外和体内都是温度敏感的(28、29)。还显示NP蛋白对于新生cRNA和vRNA的伸长和抗终止是需要的(29、30)。本发明已经发现，NP特异性siRNA抑制受感染细胞中所有病毒RNA的蓄积。NP特异性siRNA存在下，很可能新转录的NP mRNA被降解，导致抑制NP蛋白合成。没有新合成的NP，阻滞了进一步的病毒转录和复制，也阻滞了新病毒粒子产生。

副流感病毒

副流感病毒(PIV)是有包膜的，具有非节段的负链RNA基因组并属于单分子负链RNA病毒目的副粘病毒科。副流感病毒包括副粘病毒亚科的3个属中的2个，即人鼻病毒属(hPIV1和hPIV3)和腮腺炎病毒属(hPIV2和hPIV4)。作为引起婴儿和儿童下呼吸道疾病的常见起因，PIV次于RSV。PIV可导致生命周期中反复感染，通常表现为上呼吸道疾病(如感冒和/或咽喉痛)。PIV也可导致严重的下呼吸道疾病(如肺炎、支气管炎和细支气管炎)，尤其在老年人和具有无免疫应答系统的患者。只有症状疗法可用于哮吼。没有特异性的抗病毒疗法。核衣壳(NP)蛋白长509至557氨基酸，氨基酸序列相对保守。NP包被基因组RNA和反基因组RNA，每个NP单体伴有6个核苷酸。RNA复制依赖于NP对新生RNA共合成的包被。分子的N-末端75％是更高度保守的部分。其参与与P形成可溶复合体，以及随后与其它NP单体及与RNA结合以形成核衣壳。

呼吸道合胞病毒

呼吸道合胞病毒(RSV)是负-义的，有包膜的RNA病毒，属于副粘病毒科的肺病毒属。RSV感染2岁以下儿童的上呼吸道和下呼吸道，也是老年人发病和死亡的重要原因。经受RSV细支气管炎的婴儿更易于在以后发展哮鸣和哮喘。疾病可能开始于URT症状，经过1-2天快速发展为弥散性小气道疾病。RSV还导致生命周期中反复感染，通常伴有中度-严重的感冒样症状；然而，严重的下呼吸道疾病可能发生于任何年龄，尤其在老年人或具有妥协的心脏、肺、或免疫系统的人群。

有效治疗和针对RSV疫苗的研究已经经历了约40年，几乎没有成功。目前，没有临床批准的针对RSV的疫苗。核衣壳(N)蛋白是涉及在RNA基因组包膜中的主要结构蛋白，对于基因组的复制和转录很重要。它长1176个核苷酸。

人类偏肺病毒

人类偏肺病毒(hMPV)是副粘病毒科的一个成员。该病毒是负-义的RNA病毒，可分成两个基因型(A和B)，属于肺病毒亚科的偏肺病毒属。该病毒负责儿童、老年患者和无免疫应答的宿主的急性呼吸道感染。该病毒感染伴随的临床症状包括轻度至严重的呼吸问题和急性哮鸣以及细支气管炎和肺炎。核衣壳(N)基因长1,206个核苷酸，具有如N在RSV中的类似活性。

正链RNA病毒

正链RNA病毒具有完全或部分可翻译的基因组，并因此通常象裸RNA一样有感染性。这些病毒使用不依赖于帽的翻译起始、多蛋白加工和RNA复制机制以调节其病毒基因组表达。

多种病毒导致人类和动物的疾病。脊髓灰质炎病毒过去在世界范围导致了严重的脊髓灰质炎，并给试图根除此疾病的发展中国家带来了财政负担。人类鼻病毒导致了最广泛传播的病毒疾病之一，常见的感冒，对其没有有效的治疗或预防。口蹄疫病毒(FMDV)和口疮病毒导致近来在绵羊和牛的爆发，在欧洲农业产生了严重的财政风险。柯萨奇病毒导致诸如手足口综合征(主要在幼儿)、心肌炎、和球结膜等疾病。已知甲型肝炎病毒，一种肝病毒，是肝病的主要原因。

用于本发明的正链RNA病毒包括人类星状病毒、诺瓦克样病毒、冠形病毒、甲型、丙型和戊型肝炎病毒、黄热病病毒(Yellow fever virus)、脊髓灰质炎病毒、鼻病毒、脑心肌炎病毒、人类parechovirus、HIV-1、登革热病毒、西尼罗病毒、口蹄疫病毒、风疹病毒、和黄热病病毒。其它适当的正链RNA病毒对本领域技术人员是已知的。示例正链病毒核蛋白核酸序列的Genbank登记号包括AY391777、AJ3 13030、NC_001474、AY660002、D83645(衣壳)、X03700(衣壳)、和L24917(衣壳)。

人类冠状病毒

人类冠状病毒(HCoV)是冠状病毒科的成员，在环境中广泛存在，导致三分之一的常见感冒。该病毒是有包膜的病毒，具有达31kb的正链RNA基因组，这是所有RNA病毒中最大的已知基因组。人类冠状病毒导致10-30％的所有常见感冒。所有年龄组都受影响，对所有年龄组的感染率显示为是均一的。感染可为亚临床或很轻微的。更严重的下呼吸道感染报道于幼儿和老年人。相似毒株和不同毒株的再感染很常见。对一类冠状病毒的抗体不能防止另一类病毒或同一类病毒(在感染4个月后)的感染。

西尼罗病毒

西尼罗病毒(WNV)是黄病毒科的一个成员，近来在全美国蔓延，感染在2003年导致超过9000个病例和200例死亡。它在美国多个洲是病毒性脑炎的最常见原因。西尼罗病毒脑炎是一种动物传染病。病毒生命周期包括主要以鸟为宿主，以蚊子为载体。人类是偶然的宿主，不足以支持病毒的生命周期，因为低级的短暂病毒血症。然而，人类与人类之间通过血液、器官移植和哺乳的传染有过报道。目前流行病中的严重神经疾病频率表示了比通常伴有西尼罗热的毒株更有神经毒性的毒株。描述了多种神经学证据，但最典型的表现是伴有衰弱的脑炎。因此，对治疗西尼罗病毒没有显示一致的临床效应的治疗介入。

鼻病毒

人类鼻病毒是导致常见感冒和伴随的上呼吸道并发症的主要病原体。因为该病毒具有超过一百个血清型，预先暴露于鼻病毒几乎没有免疫保护，这导致更高的感染率(Hayden FG.Rhinovirus and the lower respiratory tract(鼻病毒与下呼吸道感染).Rev Med Virol.2004；14(1)：17-31)。该感染导致小的自限性疾病，然而对哮喘患者、老年患者和无免疫应答的患者，鼻病毒感染可导致致命的并发症。该病毒是非包膜的正链RNA病毒，属于小核糖核酸病毒科，具有大约7200核苷酸的基因组。该病毒基因组一从宿主细胞质释放就立刻直接作为mRNA起作用(McKnight KL，Lemon SM.The rhinovirus type14 genome contains an internally located RNA structure that is required for viral replication(鼻病毒14型基因组含有病毒复制所需的内置RNA结构).RNA；4：1569-84)。

鼻病毒可通过气溶胶或直接接触而传送。接种的主要位置是鼻粘膜，尽管在较小程度上可涉及结膜(Tan WC.Viruses in asthma exacerbations(哮喘恶化中的病毒).Curr Opin Pulm Med.2005；11：21-6)。该病毒附于呼吸道上皮并局部扩展。对此病毒的主要人类受体是胞内黏附因子-1(ICAM-1)(WeinbergerM.Respiratory infection and asthma：current treatment strategies(呼吸道感染与哮喘：目前治疗策略).Drug Discov Today.2004；9：831-7)。一些RV血清型还上调人类上皮细胞ICAM-1的表达以增加感染的易感性(Papi A，Papadopoulos NG，StanciuLA，Degitz K，Holgate ST，Johnston SL.Effect of desloratadine and loratadine onrhinovirus-induced intercellular adhesion molecular 1 upregulation and promoter activationin respiratory epithelial cells(地氯雷他定和氯雷他定对呼吸上皮细胞中鼻病毒诱导的细胞内粘附分子1上调和启动子激活的作用).JAllergy Clin Immunol.2001；108：221-8)。该病毒在鼻通道和上支气管树中复制良好，而在下呼吸道复制得不好。培养周期大约2-3天。病毒血症是不常见的但病毒大量释放。病毒释放可在患者识别感冒症状若干天前发生，在疾病的2-7天达到峰值，并可持续长达3-4周。

上气道的鼻病毒感染已经与哮喘加重相联系，研究表明这是由与变态反应原暴露或与空气污染的附加或协同相互作用导致的(Tan，同上)。对鼻病毒的受损抗病毒免疫可导致受损的病毒清除并因此导致症状延长。显示Th-2细胞因子在人类鼻病毒受体的上调中起重要作用，并可以解释鼻病毒感染后哮喘患者疾病的加重(Bianco A，Sethi SK，Allen JT，Knight RA，Spiteri MA.Th2 cytokines exert a dominant influence on epithelial cell expression of the major grouphuman rhinovirus receptor，ICAM-1(Th2细胞因子对主要的人类鼻病毒受体ICAM-1的上皮细胞表达施加重要影响).Eur Respir J.1998；12：619-26)。

登革热病毒

登革热是一种地方性的病毒疾病，影响世界上的热带和亚热带地区。登革热(DF)和其更严重的形式登革出血热(DHF)和登革休克综合症(DSS)，已经是严重的公共健康问题，近年来迅速地增加。该疾病现在在非洲、美洲、东地中海、南亚和西太平洋的超过100个国家地方性流行，威胁着超过25亿人(Gubler，D.J.1998.Dengue and dengue hemorrhagic fever(登革热和登革出血热).Clin.Microbiol.Rev.11：480-496)。世界卫生组织估计每年全世界有5000万至1亿例登革热病毒感染，导致每年250,000至500,000例DHF和24,000例死亡(Gibbons，R.v.，和D.W.Vaughn.2002.Dengue：an escalating problem(登革热：升级的问题).BMJ 324：1563-1566；世界卫生组织.1997.Denguehaemorrhagic fever：diagnosis，treatment，prevention and control(登革出血热：诊断、治疗、预防和控制)，第2版.世界卫生组织，Geneva，Switzerland)。

登革热病毒是一种产生于蚊子的黄病毒，是世界上热带和亚热带区域最流行的虫媒病毒(Gubler，D.J.1997.Dengue and dengue hemorrhagic fever：itshistory and resurgence as a global public health problem(登革热和登革出血热：其作为全球公共健康问题的历史和再现)，p.1-22.In D.J.Gubler和G.Kuno(编辑)，Dengue anddengue hemorrhagic fever(登革热和登革出血热).CAB International，New York，N.Y.)。登革热病毒是正链有包膜的RNA病毒。基因组RNA长约11kb，包括3个编码核衣壳或核蛋白(C)、膜关联蛋白(M)、包膜蛋白(E)的结构蛋白基因和7个非结构(NS)蛋白基因。这些蛋白以约3,000氨基酸的多蛋白合成，由病毒和宿主蛋白酶共翻译和翻译后加工(Duebel，v.，R.M.Kinney，和D.W.Trent.1988.Nucleotide sequence and deduced amino acid sequence of thenonstructural proteins of dengue type 2 virus.Jamaica genotype：comparative analysis of thefull-length genome(登革热2型病毒Jamaica基因型的非结构蛋白的核苷酸序列和推测的氨基酸序列：全长基因组对比分析).Virology 165：234-244)。有4种不同血清型，血清型1至4。以一种血清型感染不能提供对另一种血清型的保护。相反，通常认为二次感染或以各种登革热病毒血清型二次或多次感染是DHF-DSS的主要风险因素，因为抗体依赖性增强(Halstead，S.B.1988.Pathogenesis of dengue：challenge to molecular biology(登革热的发病机理：挑战分子生物学).Science 239：476-481)。目前有针对这种病毒的有效疫苗。

该病毒导致广谱的疾病，从隐性感染、类流感轻度未分化热、和经典DF，到更严重的高发病率和高致死的形式DHF-DSS(Gubler，D.J.1998.Dengueand dengue hemorrhagic fever(登罩热和登革出血热).Clin.Microbiol.Rev.11：480-496)。

双链RNA病毒

双链RNA病毒是多来源的。呼肠孤病毒是研究最好的dsRNA病毒之一。该科的代表感染植物、动物和昆虫，很多感染昆虫载体以及动物或植物中间宿主。这些病毒都具有双重或三重衣壳结构，其外层在内吞进入时被剥除。细胞质中的裸核颗粒能够转录加帽且非-多聚腺苷酸化的基因组-片段-长度单顺反子mRNA，经由当合成并翻译它们时伴随进入细胞质的依赖于RNA的RNA聚合酶(RdRp)活性。病毒产物蓄积为病毒发生基质：病毒结构蛋白和聚合酶蛋白以及mRNA的联合导致组装不成熟的颗粒，其中mRNA转录以得到负链RNA分子，它们一起碱基配对。中间产物和内部衣壳蛋白的重要性示于轮状病毒的实施例。

用于本发明的双链RNA病毒包括轮状病毒、呼肠孤病毒、哺乳动物正呼肠弧病毒(orthoriovirus)和科罗拉多蜱热病毒。其它合适的双链RNA病毒对本领域技术人员是已知的。示例双链病毒核蛋白核酸序列的Genbank登记号包括K02086(VP6)和X14942(VP2)。

轮状病毒

轮状病毒是呼肠孤病毒科的一个成员，是导致婴儿和幼儿急性胃肠炎的重要原因(Kapikian，A.Z.2001，Rotaviruss，p.1787-1833.Fields virology，第4版.Lippincott/The Williams&Wilkins Co.，Philadelphia，Pa.)。病毒粒子是二十面体，由三个蛋白中心层和双链RNA(dsRNA)的11个片段的基因组组成(Prasad，B.V.1988，J.Mol.Biol.199：269-275)。感染性三层颗粒(TLP)的外层由糖蛋白VP7和突起蛋白VP4构成。中间层由VP6三聚物构成，内层由核晶格蛋白VP2构成。位于VP2晶格至高点的是RNA依赖性RNA聚合酶(RdRp)VP1和mRNA-加帽酶VP3的各拷贝(Lawton，J.A.，1997，J.Virol.71：7353)。

形成病毒中间层的VP6通过其与外层蛋白VP7和VP4，与内层蛋白VP4和VP7，以及与内层蛋白VP2的相互作用，整合了病毒的两种主要功能：进入细胞和内源转录。VP6本身尽管没有任何酶功能，但对于基因组的内源转录是关键的。Cryo-EM研究显示，新生mRNA转录子通过VP6层中的I型通道特异性地离开(Lawton，J.A.，2000，Adv.Virus Res.55，185-229)。基于拟-原子模型对VP6层的突变分析进一步证明，VP6三聚体在VP2上的合适组装对内源转录是绝对需要的。位点-特异性氨基酸置换部分或完全地终止了转录酶活性(Charpilienne，A.，2002，J.Virol.76，7822-7831)。转录子经由衣壳层(轮状病毒VP6层的等价物)通道的离开显示为dsRNA病毒的通常主题。该层中的区域已经显示出还作用为转录反应的底物池(substratesinks)。

VP2形成与外部VP6层和内部基因组RNA相互作用的最内层。VP2通过其N-末端残基表现结合RNA的能力。VP2在维持RNA链之间适当距离以允许基因组RNA在转录过程中围绕转录复合体移动中起重要作用(Pesavento，J.B.，2001，Proc.Natl.Acad.Sci.U.S.A.，98，1381-1386)。因此，VP2的一个主要功能是引导基因组的结构组建，使其对其内源转录有传导性。

RNA诱导实体-siRNA和shRNA分子

本发明的特征为siRNA分子，制备siRNA分子的方法和使用siRNA分子的方法(如预防和/或治疗方法和研究方法)。siRNA分子长度可从约10-60核苷酸或更多核苷酸(或核苷酸类似物)，约15-25个核苷酸(或核苷酸类似物)，或约19-23个核苷酸(或核苷酸类似物)。siRNA分子的核苷酸(或核苷酸类似物)长度可为约10-20、20-30、30-40、40-50、15、16、17、18、19、20、21、22、23、24、25、26、27、28或29个。在优选实施方案中，siRNA分子长度为19个核苷酸。应理解上述范围包括的所有范围和值都在本发明范围内。一般，长dsRNA(超过60个核苷酸)是较不优选的，因为发现它们可诱导哺乳动物细胞如人类细胞中的细胞死亡(称为“干扰素应答”)。siRNA可优选地包括5’末端磷酸和3，约1或2核苷酸的短突出端。在优选实施方案中，诱导RNAi的实体可为短发夹siRNA(shRNA)或表达的shRNA。这种shRNA的例子和制备方法在实施例中讨论。在另一实施方案中，siRNA可在siRNA复合体中与一种或多种蛋白联合。

提供本发明的siRNA分子以通过如下结合方式至少部分地结合靶病毒转录子来减少宿主细胞中病毒基因表达：导致靶病毒转录子被宿主细胞机器破坏。因此，本发明的siRNA分子包括序列，该序列足够互补于病毒核蛋白基因的一部分以介导如本文所定义的RNA干扰(RNAi)，即siRNA具有足够特异性以由RNAi机器或过程激发靶RNA降解的序列。siRNA可被设计为反义链的每个残基互补于靶分子中的残基。或者，可在分子内形成置换以增加所述分子的稳定性和/或增强所述分子的加工活性。可在链的内部形成置换，或在链末端的残基形成置换。

siRNA引导的靶RNA裂解反应是高度序列特异性的。通常，含有与靶基因一个部分相同的核苷酸序列的siRNA是优选用于抑制的。由于本发明的siRNA通常以双链分子提供，siRNA反义链的相同性和互补性可相对于靶转录子确定。因此，如此处所用，与编码病毒核蛋白的核酸的一部分相同的核酸序列的公布包括双链siRNA的两条链。然而，认识到siRNA与靶基因之间100％的序列相同性不是实践本发明所必需的。因此本发明的优点是，能够经受序列变异，这可能是因为遗传突变、菌株多态性、或进化趋异。例如，相对于靶序列带有插入、缺失和单点突变的siRNA对抑制是有效的。或者，带有核苷酸类似物置换或插入的siRNA序列对抑制是有效的。而且，siRNA的所有位点不是同等贡献于识别靶。siRNA中心的错配是最重要的并可实质上破坏靶RNA裂解。相反，siRNA的3’核苷酸(如siRNA反义链的3’核苷酸)通常不显著贡献于特异性识别靶。尤其是，与靶RNA(如引导序列)互补的siRNA序列的3’残基通常对于靶RNA裂解不是关键的。

本领域已知的是不是所有siRNA在减少或抑制任何特定靶基因表达中同等地有效。(见，T.，等，Nucleic Acids Res.，30(8)：1757-1766，报道不同siRNA效力的变异性)，采用多种考虑因素以增加选择的siRNA有效的可能性。例如，选择外显子而不是内含子内的靶部分可为优选的。siRNA通常可根据描述于以下的原理来设计：Technical Bulletin # 003-Revision B，“siRNA Oligonucleotides for RNAi Applications(用于RNAi应用的siRNA寡核苷酸)”和Technical Bulletin#4，Dharmacon Research，Inc.，Lafayette，CO80026，RNA试剂的供应商。Dharmacon的The RNAi Technical Reference &Application Guide(RNAi技术参考&应用指南)含有多种涉及siRNA设计参数、合成等信息，通过引用合并于此。其它可采用的设计考虑因素描述于Semizarov，D.，等，Proc.Natl.Acad.Sci，Vol.100，No.11，pp.6347-6352.

可经由本领域已知的序列比较和比对算法来确定序列相同性。为了确定两个核酸序列(或两个氨基酸序列)的相同性百分比，为了优化比较目标进行序列比对(如，可在第一序列或第二序列引入缺口以优化比对)。然后比较相应核苷酸(或氨基酸)位置上的核苷酸(或氨基酸残基)。当第一序列中的位置由第二序列中相应位置的相同残基占据时，在此位置分子是相同的。两个序列之间相同性百分比是序列间分享相同位置的函数(即％同源性＝相同位置的数目/位置总数目×100)，任选地对引入缺口的数目和/或引入缺口的长度罚分。

可使用数学算法来实现序列的比较和两序列间相同性百分比的确定。在一个实施方案中，在所比对序列的具有足够相同性的部分产生比对，而在具有较低相同性的部分不产生(即，局部比对)。用于序列比较的局部比对算法的优选非限制性例子是Karlin & Altschul，Proc.Natl.Acad.Sci.USA 87：2264-68(1990)的算法，调整为Karlin & Altschul，Proc.Natl.Acad.Sci.USA 90：5873-77(1993)。这样的算法并入Altschul，等，J.Mol.Biol.215：403-10(1990)的BLAST程序(2.0版本)中。在一个实施方案中，该算法通过引入合适的缺口而优化，在所比对序列的长度上确定相同性百分比(即，缺口比对)。为了获得比较目的的缺口比对，Gapped BLAST可如Altschul，等，Nucleic Acids Res.25(17)：3389-3402(1997)描述的使用。在另一个实施方案中，通过引入合适的缺口而优化比对，在所比对的序列的全长确定相同性百分比(即，总体比对)。用于序列总体比较的数学算法的优选非限制性例子是Myers和Miller，CABIOS(1989)的算法。这样的算法并入ALIGN程序(2.0版本)，其是GCG序列比对软件包的一部分。当使用ALIGN程序用于比较氨基酸序列时，可使用PAM120重量残基平台、缺口长度罚分为12，缺口罚分为4。

siRNA(如siRNA的反义链)与靶基因部分之间，大于80％的序列相同性是优选的，如84％、89％、91％、92％、93％、94％、95％、96％、97％、98％、99％、或甚至100％。siRNA约19-25核苷酸的情况，如至少16-21相同核苷酸是优选的，更优选至少17-22相同核苷酸，甚至更优选至少18-23或19-24相同核苷酸。换言之，在长约19-25核苷酸的siRNA，具有不超过约4个错配的siRNA是优选的，优选地不超过3个错配，更优选地不超过2个错配，甚至更优选地不超过1个错配。例如，siRNA含有靶序列中具有1、2、3、或4错配的反义链。

或者，siRNA可根据功能定义，如包括能与靶基因转录子一部分杂交的核苷酸序列(或寡核苷酸序列)(如，400 mM NaCl，40 mM PIPES pH 6.4，1mM EDTA，50℃或70℃杂交12-16小时；然后洗涤)。其它优选的杂交条件包括在70℃、1×SSC或50℃、1×SSC杂交，50％甲酰胺，然后在70℃、0.3×SSC洗涤，或在70℃、4×SSC或50℃、4×SSC杂交，50％甲酰胺，然后在67℃、1×SSC洗涤。预期长度小于59碱基对的杂合体的杂交温度应该比杂合体的变性温度(Tm)低5-10℃，Tm根据以下方程来确定。对于长度小于18碱基对的杂合体，Tm(℃)＝2(A+T碱基的#)+4(G+C碱基的#)。对于长度18至49碱基对的杂合体，Tm(℃)＝81.5+16.6(log10[Na+])+0.41(％G+C)(600/N)，其中N是杂合体中碱基的数目，[Na+]是杂交缓冲液中钠离子的浓度(1×SSC的[Na+]＝0.165M)。对多核苷酸杂交的严格条件的其它例子提供于Sambrook，等，1989，MolecularCloning：A Laboratory Manual，Cold Spring Harbor Laboratory Press，ColdSpring Harbor，N.Y.，chapter 9 and 11，和Current Protocols in MolecularBiology，1995，F.M.Ausubel，等编辑，John Wiley&Sons，Inc.，sections 2.10和6.3-6.4，在此并入。相同核苷酸序列的长度可为至少约10、12、15、17、20、22、25、27、30、32、35、37、40、42、45、47或50碱基。

在一个实施方案，本发明的RNA分子被修饰，以至提高在用于细胞培养的血清或生长培养基中的稳定性。为了增强稳定性，3’-残基可被稳定以避免降解，如可选择它们以使其由嘌呤核苷酸如腺嘌呤或鸟嘌呤核苷酸组成。或者，嘧啶核苷酸被修饰的类似物的置换，如尿嘧啶被2’-脱氧胸腺嘧啶的置换是耐受的并不影响RNA干扰的效力。例如，没有2’羟基可显著增强组织培养基中siRNA的核酶抗性。

在本发明优选实施方案中，RNA分子可含有至少一个修饰的核苷酸类似物(或类似物)。核苷酸类似物可位于靶特异性活性如RNAi介导活性大致不受影响的位置，如RNA分子5’-端或3’-端的区域。尤其是，可通过并入修饰的核苷酸类似物使得末端稳定化。优选的核苷酸类似物包括糖-和/或骨架-修饰的核糖核苷酸(即，包括对磷酸-糖骨架的修饰)。例如，天然RNA的磷酸二酯键可被修饰以包括至少一个氮或硫杂原子。在优选的骨架修饰核糖核苷酸中，连接于相邻核糖核苷酸的磷酸酯基团被修饰基团如硫代磷酸基团代替。在优选的糖修饰核糖核苷酸中，2’OH基团由选自H、OR、R、卤素、SH、SR、NH₂、NHR、NR₂或ON的基团代替，其中R是C₁-C₆烷基、链烯基或炔基，卤素为F、CI、Br或I。

优选的还有核碱基-修饰的核糖核苷酸，即，含有至少一个非天然产生的核碱基而不是天然产生的核碱基的核苷酸。可修饰碱基以阻滞腺苷脱氨酶的活性。示例性修饰核碱基包括但不限于，在5-位置修饰的尿苷和/或胞苷，如，5-(2-氨基)丙基尿苷、5-溴尿苷；在8位置修饰的腺苷和/或鸟苷，如，8-溴鸟苷；去氮核苷酸，如，7-去氮-腺苷；O-和N-烷基化核苷酸，如，N6-甲基腺苷是合适的。应注意上述修饰可以结合。

在一些实施方案中，siRNA可通过以修饰核苷酸置换至少一个核苷酸而被修饰。siRNA与核蛋白转录子靶序列相比可具有一个或多个错配而仍然介导RNAi，如以下实施例所证明的。

本发明核蛋白引导siRNA介导RNAi的能力当考虑此处所提供病毒的一些基因的快速突变率时是尤其有利的，如流感病毒基因。由于发明人认识到核蛋白基因通常与其它病毒基因相比具有较低突变率，发明人提供了核蛋白基因作为RNAi靶的用途。而且，在本发明一些实施方案中，siRNA靶向于病毒核蛋白基因的保守区域。本发明包括多个实施方案，其进一步影响此能力，通过例如合成患者特异性siRNA或质粒，和/或沿着核蛋白基因交错引入多个siRNA。在一个实施方案，核蛋白基因的高度和/或中度保守的区域被靶向，如以下更详细讨论的。在其它实施方案中，生物样品获自患者。如此处所用，生物样品是获自含有病毒核酸的患者的任何物质。例如，获得宿主患者的一种或多种受感染细胞，将其中病毒核蛋白基因的基因组测序或以其它方式分析以选择或合成一个或多个相应得siRNA、质粒或转基因。

siRNA 的制备

在一个实施方案中，体内或体外合成siRNA。细胞的内源RNA聚合酶可介导体内转录，或克隆的RNA聚合酶可用于体内或体外转录。对于从体内转基因或表达构建体的转录，调节区域(如启动子、增强子、沉默子、或剪接供体和受体)可用于转录siRNA。通过在器官、组织、或细胞类型中特异性转录；环境条件(如感染、应激、温度、滑雪诱导物)的刺激；和/或在发育阶段或年龄的工程转录，可靶向抑制。通过引入重组构建体至受精卵、胚胎干细胞、或其它来自合适生物体的多潜能细胞，可产生表达来自重组构建体的siRNA的转基因生物体。

此外，不仅siRNA可用于产生细胞内的多RNA，细胞内还可由宿主细胞酶复制和扩增siRNA。Alberts，等，The Cell 452(第4版.2002)。

可酶解或部分/完全有机合成来产生RNA，可经由体外酶或有机合成引入任何修饰的核苷酸。在一个实施方案，化学制备siRNA。合成RNA的方法是本领域已知的，尤其是Verma和Eckstein，Ammul Rev.Biochem.67：99-134(1998)所述的化学合成方法。另一个实施方案中，酶解制备siRNA。例如，可通过酶处理具有与期望靶RNA足够互补的长dsRNA来制备siRNA。长dsRNA的处理可在体外实现，例如使用合适的细胞裂解酶，可经由凝胶电泳或凝胶过滤随后纯化ds-siRNA。在一个示例实施方案中，可从混合物由溶剂或树脂提取、沉淀、电泳、色谱法或其组合纯化RNA。或者，可使用RNA而不纯化或最少地纯化以避免由于样品处理的损失。

还可由从合成DNA模板或从重组菌分离的DNA质粒的酶转录而制备RNA。通常，使用噬菌体RNA聚合酶，如T7、T3或SP6 RNA聚合酶(Milligan&Uhlenbeck，Methods Enzymol.180：51-62(1989))。RNA可干燥以贮存或溶解于水溶液。该溶液可含有缓冲剂或盐以抑制退火，和/或促进单链的稳定。

siRNA载体

本发明的另一方面包括一种载体，其表达一种或多种包括与核蛋白基因组的一部分足够互补以介导RNAi的序列的siRNA。该载体可体内给药以通过表达一种或多种siRNA拷贝而起始RNAi治疗或预防。在一个实施方案，在质粒载体中表达合成的shRNA。另一实施方案中，质粒在体内复制。在另一实施方案中，载体可为病毒载体，如逆转录病毒载体。这种质粒和其制备方法的例子表示于实施例。载体和质粒的使用是有利的，因为载体比合成的siRNA稳定，并因此实现siRNA的长期表达。

一些靶病毒快速突变并可能导致在一些情况下可妨碍RNAi的即使一个核苷酸的错配。因此，在一个实施方案中，关注了这样载体：其表达多种siRNA以提高足以介导RNAi的同源性的概率。优选地，这些siRNA沿核蛋白基因交错分布，或者集中于核蛋白基因的一个区域。例如，多种siRNA可导向核蛋白基因长约200核苷酸并包括核蛋白基因3’端的区域。在一个实施方案中，载体表达的一种或多种siRNA是shRNA。siRNA可沿着核蛋白基因一个部分交错，或靶向核蛋白基因的不同部分。在一个实施方案中，载体编码约3 siRNA，更优选约5 siRNA。siRNA可靶向于核蛋白基因的保守区域。

引入RNA的方法、载体和宿主细胞

引入本发明物质(如siRNA、载体或转基因)的物理方法包括注射含有所述物质的溶液，所述物质覆盖的颗粒的轰击、在所述物质的溶液中浸泡细胞或有机体，或在所述物质存在下对细胞膜电穿孔。包入病毒粒子的病毒构建体将实现向细胞引入表达构建体和表达构建体编码的RNA包括siRNA的转录。可使用本领域已知的将核酸引入细胞的其它方法，如脂质介导的载体转运，化合物如磷酸钙介导的转运，等等。因此，siRNA可与表现一种或多种其它活性的组分一起引入，所述活性如增强siRNA的细胞摄取，抑制两条siRNA链间的退火，稳定单链，或以其它方式增加对靶基因的抑制。

所述物质可直接引入细胞(即胞内地)；或胞外地引入体腔、细胞间质，引入有机体的循环，口服引入，吸入，或通过将细胞或有机体浴于含有RNA的溶液而引入。所述物质可引入血管循环或血管外循环、血液或淋巴系统、和脑脊髓液。

细胞可以在递送所述物质时感染靶病毒或在物质递送之后暴露于靶病毒。该细胞可能衍生自任何有机体或包含在任何有机体中。细胞可能来自种系、体细胞、全能或多能、分裂或非分裂、薄壁组织或上皮组织，永生化的或变异的等等。细胞可为干细胞或分化细胞。

根据特定靶基因和所递送的双链RNA物质的剂量，该方法可提供靶基因的部分或完全功能丧失。基因表达在至少50％、60％、70％、80％、90％、95％或99％或更多的靶细胞中减少或丧失是典型的。基因表达的抑制是指病毒蛋白、RNA、和/或DNA水平的不存在(或可观察到的降低)。特异性是指抑制靶基因而不对其它基因尤其是宿主细胞的其它基因产生影响的能力。抑制的结果可通过检查细胞或有机体的外部特征或生化技术而证实，所述生化技术如RNA溶液杂交、核酶保护、Northern杂交、以微阵列监控反转录基因表达、抗体结合、酶联免疫吸附测定(ELISA)、整合检测(integration assay)、Western点杂交、放射免疫测定(RIA)、其它免疫测定、以及荧光活化细胞分析(FACS)。

对于细胞系或完整生物体中RNA介导的抑制，通过使用其蛋白产物容易检测的报告基因或药物抗性基因方便地检测基因表达。这样的报告基因包括乙酰羟基酸合成酶(AHAS)、碱性磷酸酶(AP)、β半乳糖苷酶(LacZ)、β糖玻璃酸酶(GUS)、氯霉素乙酰转移酶(CAT)、绿色荧光蛋白(GFP)、辣根过氧化物酶(HRP)、萤光素酶(Luc)、胭脂碱合成酶(NOS)、章鱼碱合成酶(OCS)、及其衍生物。有多种选择性标记，其赋予对氨苄西林、博来霉素、氯霉素、庆大霉素(gentarnycin)、潮霉素、卡那霉素、林可霉素、甲氨喋呤、草丁膦、嘌呤霉素、和四环素的抗性。根据检测，基因表达量的定量使得人们能确定与没有根据本发明处理的细胞相比，抑制程度为大于10％、33％、50％、90％、95％或99％。给药siRNA之后较低剂量注射物质和较长时间可导致细胞小部分的抑制(如靶细胞的至少10％、20％、50％、75％、90％或95％)。

细胞中基因表达的定量可显示靶RNA蓄积或靶蛋白翻译水平的类似量的抑制。作为例子，抑制的效力可通过评价细胞中基因产物的量而确定；以具有用于抑制双链RNA区域以外的核苷酸序列的杂交探针而检测RNA，或翻译的多肽可通过针对该区域多肽序列产生的抗体而检测。

siRNA可以允许递送每细胞至少一个拷贝的量而引入。物质的更高剂量(如每细胞至少5、10、100、500或1000拷贝)可产生更有效的抑制；更低剂量也可用于具体应用。

诊断方法和试剂盒

本发明包括一种识别方法，即如病毒导致的感染等传染病的基于RNAi的治疗，可期望地并入诊断步骤，该诊断步骤确定需要治疗的患者是否感染了对一种或多种诱导RNAi的实体抑制敏感的传染原。“对抑制敏感”是指传染原的一种或多种生物活性可通过给药诱导RNAi的实体于患者而有效抑制。优选地抑制传染原的复制、病原性、传播和/或生产。例如，当诱导RNAi的实体以耐受剂量给药于患者时，传染原的复制、病原性、传播或生产优选地被抑制至少25％。优选地该抑制足以产生治疗上有用的效果。

流感病毒用于非限制性例子来说明本发明的诊断方法，其被定制以允许选择适于患有感染的患者的诱导RNAi的实体。然而应理解，此处公开的方法适于此处所述的任何病毒或将被本领域技术人员识别的任何病毒。所选择的诱导RNAi的实体当然也可能被给药以预防，例如给药于接触了受感染个体的个体，而不考虑这些个体是否已经发展了感染症状。

本发明因此提供了诊断病毒感染并确定患者是否感染病毒的方法。在一些实施方案中，该方法包括确定患者是否感染了病毒，该病毒由本发明的靶向病毒核蛋白转录子的一种或多种诱导RNAi的实体抑制。例如，从怀疑具有病毒感染如流感的患者获得样品(如痰、唾液、鼻洗液、鼻拭物、气管洗液、支气管肺泡灌洗(BAL)液、生物活检样本)。样品可经受一个或多个加工步骤。任何这样的加工样品可认为获自患者。分析样品以确定其是否含有病毒特异性核酸，尤其是核蛋白转录子。“病毒特异性核酸”是任何源自病毒或衍生自病毒的任何核酸或其互补物，并可作为样品中病毒存在的指征，且任选地用于识别毒株和/或病毒基因的序列。核酸可已经在分离后经受了加工步骤。例如，它可为反转录的、扩增的、裂解的，等等。在一些实施方案中，样品中存在的病毒特异性核酸或其互补物的序列与RNAi诱导剂如siRNA或shRNA的反义链或有义链的序列进行比较。“比较”一词以宽泛的含义使用，指任何评价序列的方法，例如，可确定该序列在一个或多个位置是否与参考序列相同或不同，或可由其评价差异的程度。

可使用任何广泛多样的基于核酸的检测。在一些实施方案中，诊断检测使用一种核酸，该核酸包括有利和/或高度保守的靶部分或其互补物，或有利和/或高度保守部分或其互补物的片段。在一些实施方案中，例如在如下所述的检测中，该核酸作为扩增引物或杂交探针。

在一些实施方案中，扩增样品中流感特异性核酸。等温靶扩增方法包括转录介导的扩增(TMA)、自动维持序列扩增(3SR)、基于核酸序列的扩增(NASBA)、和其变化。可使用本领域已知的任何多种方法进行检测或比较，如基于扩增的检测、杂交检测、引物延伸检测(如等位基因特异性引物延伸，其中不同流感病毒株的相应靶部分对基因的不同等位基因是同源的)、寡核苷酸连接检测(美国专利No.5,185,243、5,679,524和5,573,907)、裂解检测、异源双链体追踪分析(HTA)检测等。例子包括Taqman^检测、Applied Biosystems(美国专利No.5,723,591)。也可采用循环探针技术(CPT)，其是基于信号扩增或探针扩增而不是靶扩增的核酸检测系统(美国专利No.5,011,769、5,403,711、5,660,988、和4,876,187)。侵入性裂解检测，如Invader^检测(Third Wave Technologies)，描述于Eis，P.S.等，Nat.Biotechnol.19：673，2001，可用于检测流感特异性核酸。可使用基于分子信标的检测(美国专利No.6,277,607；6,150,097；6,037,130)或荧光能量转移(FRET)。分子信标是寡核苷酸发夹，在结合于完美匹配的模板时经历构象变化。

在一些实施方案中，该检测确定样品中的流感特异性核酸是否包括与诱导RNAi的实体的有义链或反义链相同或不同的部分。任选地，如果有确切的差异的话则鉴别确切差异。该信息用于确定流感病毒是否对诱导RNAi的实体抑制敏感。除了以上所述的，用于对传染原检测和/或基因分型的合适检测描述于Molecular Microbiology：Diagnostic Principles andPractice(分子生物学：诊断原理与实践)，Persing，D.H.，等(编辑)Washington，D.C.：ASM Press，2004.

诊断检测可采用此处所述的任何核酸。在本发明一些实施方案中，该核酸包括不是与核蛋白转录子大致互补或大致相同的核酸部分。例如，核酸可包括引物结合位点(如用于通用测序引物或扩增引物的结合位点)、杂交标记(可能例如用于从含有其它核酸的样品分离该核酸)等。在本发明一些实施方案中，该核酸包括非核苷酸部分。该非核苷酸部分可连接于核酸的末端核苷酸，如在3’端。该部分可保护核酸不受降解。在一些实施方案中，该非核苷酸部分是可检测的部分，如荧光染料、放射性原子、荧光能量转移(FRET)对、猝灭剂等。在一些实施方案中，该非核酸部分是结合部分，如生物素或抗生物素蛋白。在一些实施方案中，该非核酸部分是半抗原，如地高辛、2，4-二硝基苯基(TEG)等。在一些实施方案中，该非核酸部分是对分离核酸有用的标记。

在一些实施方案中，核酸连接于支持物，如一种微粒如珠，其任选是磁性的。本发明进一步提供阵列，其包含本发明的多种核酸，例如至少10、20、50等。该核酸共价或非共价地连接于支持物，如大致平面的支持物如载玻片。见美国专利No.5,744,305；5,800,992；6,646,243。

从实验或从此前对具有核蛋白基因内特定序列的病毒治疗的实验中获得的信息也可用于确定该病毒是否对所给的诱导RNAi的实体或其组合的抑制敏感。敏感性信息还可包括例如基于核蛋白病毒序列与抑制剂的反义链之间存在的任何错配的期望效应的理论预测。

本发明提供了用于检测病毒感染的诊断试剂盒。一些试剂盒包括本发明的一种或多种核酸。一些试剂盒包括可用于检测包括用于RNAi的优选靶部分的部分的核蛋白病毒转录子的一种或多种核酸。试剂盒可包括选自以下组的一项或多项：探针、引物、序列特异性寡核苷酸、酶、底物、抗体、核苷酸群体、缓冲剂、阳性对照和阴性对照。可标记核苷酸。例如，可提供荧光标记的核苷酸的一种或多种群体，如dNTP、ddNTP等。

探针可为包括靶部分全部或部分的核酸，如高度保守或有利保守的核蛋白靶部分，或其互补物，或与靶部分至少80％相同或互补，如100％相同或互补。在一些实施方案中，提供了多种探针。这些探针在一个或多个位置上不同，可用于确定在这些位置上核蛋白病毒的准确序列。例如，探针可不同地杂交于转录子(如只有当探针与转录子的靶部分100％互补时才发生杂交)。本发明的试剂盒可包括标本收集材料，如拭子、试管等。试剂盒的组分可包装于单个导管或试管，其通常提供于容器中，如使用商业销售的塑料或泡沫聚苯乙烯容器，伴有指导试剂盒使用的说明。处理方法

本发明提供了用于处理有患病毒风险(或易于患病毒)的患者或具有病毒的患者的预防方法和治疗方法。此处所用“处理(treatment)”或“处理(treating)”定义为应用或给药治疗剂(如siRNA或载体或编码其的转基因)于患者，或应用或给药治疗剂于从患者分离的组织或细胞系，该患者具有病毒，目的为治愈、愈合、减轻、缓解、改变、补救、改善、改进或影响病毒或病毒症状。术语“处理(treatment)”或“处理(treating)”此处也用于指预防地给药药剂，如以针对病毒而接种。

考虑到处理的预防方法和治疗方法，这样的处理可基于药物基因组学领域获得的知识而特殊地定制或修改。此处所用的“药物基因组学”是指应用基因组技术如基因测序、统计遗传学和基因表达分析于临床开发和市场的药物。更具体地，该术语是指研究患者的基因如何确定其对药物的反应(如患者的“药物反应表型”或“药物反应基因型”)。因此，本发明的另一方面提供了定制个体的预防处理或治疗处理的方法，使用根据该个体的药物反应基因型的本发明的靶基因分子或靶基因调节物。

在相关实施方案中，两种或多种不同诱导RNAi剂的群体给药于患者，患者可为病毒的宿主。在一个实施方案中，两种或多种RNAi诱导剂的群体包括含有引导链的剂，引导链的序列与特定病毒多种毒株的相同高度保守区大致互补(优选100％互补)。在另一实施方案中，两种或多种RNAi诱导剂的群体包括含有引导链的物质，引导链的序列与同一病毒毒株的不同高度保守区大致互补(优选100％互补)。在另一实施方案中，两种或多种RNAi诱导剂的群体包括含有引导链的物质，引导链的序列与特定病毒(如，流感病毒)多种毒株的相同高度保守区大致互补(优选100％互补)，并且RNAi诱导剂包括含有引导链的物质，引导链的序列与同一病毒毒株的不同高度保守区大致互补(优选100％互补)。

预防方法

在一个方面，本发明提供了一种防止患者病毒感染或病毒感染相关疾病的方法，通过给药于患者预防有效的药剂，该药剂包括此处所讨论的任何siRNA或载体或转基因。预防剂的给药可发生在表现出病毒感染的典型症状如病毒感染之前。

在优选实施方案中，预防有效的剂在暴露于靶病毒之前给药于患者。在另一实施方案中，该剂在暴露于靶病毒之后给药于患者以延迟或抑制其发展，或阻止其整合入健康细胞或不含有原病毒的细胞的DNA。优选地，抑制或阻止靶病毒信息。此外或可替代地，抑制或阻止靶病毒复制是优选的。在一个实施方案中，siRNA在靶病毒RNA复制的早期阶段降解靶病毒RNA，例如在进入细胞之后立即发生。以这种方式，药剂可阻止患者的健康细胞不受感染。在另一实施方案中，siRNA在复制的后期降解病毒MRNA。在这些方法中可采用此处所述任何策略，例如给药表达多种足够互补于病毒核蛋白基因以介导RNAi的siRNA的载体。

治疗方法

本发明的另一方面涉及为了治疗目的而调节靶基因表达、蛋白表达或活性的方法。因此，在一个示范实施方案中，本发明的调节方法包括将病毒感染的细胞接触治疗剂(如siRNA或编码其的载体或转基因)，该治疗剂对病毒基因组的一部分是特异性的，从而介导RNAi。这些调节方法可在体外进行(如以所述剂培养细胞)、或可选择地，在体内进行(如给药所述剂于患者)。该方法可在体外进行，然后将产物引入患者(如基因治疗)。

本发明的治疗方法通常包括经由给药药剂于病毒(如流感)感染的患者而开始RNAi。该药剂可包括一种或多种siRNA、一种或多种siRNA复合体、表达一种或多种siRNA(包括shRNA)的载体、或编码一种或多种siRNA的转基因。本发明的治疗方法能减少病毒产生(如病毒滴度或原病毒滴度)约30-50倍，优选约60-80倍，更优选约(或至少)90倍、100倍、200倍、300倍、400倍、500倍或1000倍。

此外，本发明的治疗剂和方法可与转录后方法(如，以核酶和/或反义siRNA)用于共治疗。

双重预防和治疗方法

在一个优选方法中，对已经暴露于靶病毒的患者进行对靶病毒的双向攻击。通过在病毒复制的早期阶段和整合入宿主细胞基因组之前降解病毒，可预防和治疗地处理受感染的患者，并延迟靶病毒开始复制的细胞中的病毒复制。

本领域技术人员可易于确定对所用组合物的确切制剂的合适的给药剂量、方案、和方法，以达到对具体患者的期望的“有效水平”。通过对合适的患者样品(如血液和/或组织)的直接分析(如分析化学分析)或间接分析(如病毒感染的替代指征)，本领域技术人员可易于确定并使用本发明化合物的“有效水平”的合适指征。

用于治疗处理病毒感染时，本发明的预防或治疗药物组合物可包含其它药物，结合根据本发明的载体。除了以上所述的以外，这些附加药物的进一步示范例子可包括抗病毒化合物、免疫调节剂、免疫刺激剂、抗生素、和其它能用于治疗病毒感染的药剂和治疗方案(包括识别为替代药物的)。免疫调节剂和免疫刺激剂包括但不限于各种白介素、CD4、细胞因子、抗体制品、输血、和输细胞。

药用组合物

本发明涉及上述诱导RNAi的实体用于预防和治疗处理病毒感染，如下所述。因此，本发明的药剂可并入适于给药的药物组合物。这种组合物通常包括该药剂和药学可接受的载体。

本发明的药物组合物配制为与其预期的给药途径相容。给药途径的例子包括口服、吸入、鼻内、非胃肠(如静脉内、皮内、皮下、腹膜内和肌内)、经皮(局部)、和跨粘膜给药。用于非胃肠、皮内或皮下应用的溶液或悬浮液可包含以下成分：无菌稀释剂如用于注射的水、盐水溶液、不挥发油、聚乙二醇、甘油、丙二醇或其它合成溶剂；抗菌剂如苯甲醇或对羟基苯甲酸甲酯；抗氧化剂如抗坏血酸或亚硫酸氢钠；螯合剂如乙二胺四乙酸(EDTA)；缓冲剂如乙酸盐、柠檬酸盐或磷酸盐，以及调节涨度的剂如氯化钠或葡萄糖。可用酸或碱来调节pH，如盐酸或氢氧化钠。非胃肠制剂可封闭于安瓿、一次性注射器或玻璃或塑料制的多剂量小瓶中。

适于注射的药物组合物包括无菌水溶液(当可水溶时)或用于临时制备无菌可注射溶液或分散剂的分散剂和无菌粉末。对静脉内注射，合适的载体包括生理盐水、抑菌水、Cremophor EL^TM(BASF，Parsippany，N.J.)或磷酸缓冲盐(PBS)。在所有情况下，组合物必须是无菌的并流动到容易注射的程度。它在制备和贮藏条件下必须是稳定的，并被保存而不受微生物如细菌和真菌的污染作用。载体可为溶剂或分散介质，其含有例如水、乙醇、聚醇(如甘油、丙二醇、和液态聚乙二醇等)、及合适的混合物。可通过如使用包衣(如卵磷脂)，通过维持分散情况下期望的粒径尺寸和使用表面活性剂而维持合适的流动性。通过各种抗菌剂和抗真菌剂(如对羟基苯甲酸酯、氯丁醇、苯酚、抗坏血酸、硫柳汞等)而达到防止微生物的作用。在许多情况下，优选的是组合物中包括等渗剂(如蔗糖、聚醇如甘露醇和山梨醇、氯化钠)。注射组合物的延长吸收可通过在组合物中包括一种延迟吸收的剂(如单硬脂酸铝和明胶)而达到。

通过将在合适溶剂中的需要量的活性化合物如所需地与以上所列的一种成分或其组合合并，然后过滤灭菌而制备无菌注射溶液。通常，将活性化合物并入含有碱性分散介质的无菌载体和以上所列的所需其它成分，从而制备分散液。在用于制备无菌注射溶液的无菌粉末的情况，制备的优选方法是真空干燥和冻干，其产生活性成分的粉末，并带有来自以上无菌过滤溶液的任何其它期望成分。

吸入给药是指诱导RNAi的实体经由鼻或嘴吸入而直接进入呼吸系统并进入肺。该实体是以裸露形式或伴有递送剂。在一些实施方案中，RNAi诱导剂以有效量给药以治疗或预防影响呼吸系统的疾病，如呼吸道病毒感染，并导致血液中的吸收最小，从而使得RNAi诱导剂的系统递送最少。尤其是，本发明提供了含有诱导RNAi的实体的干粉组合物，其优选以气雾化喷雾的形式递送，该喷雾来自含有合适喷射剂如二氧化碳等气体的加压容器或分散器或喷雾器。在一些实施方案中，该递送系统适于递送组合物进入患者(如动物或人类)的主要气道(气管和支气管)和/或更深地进入肺(细支气管和/或肺泡)。本发明还包括使用鼻喷雾递送包含诱导RNAi的实体的组合物。根据本发明的一些实施方案，促进核酸被呼吸系统中细胞摄取的递送剂也包括在药物组合物中。然而，本发明还发现没有特异性递送剂时，当RNAi诱导剂经由呼吸道被递送至呼吸系统时，其可有效抑制流感病毒。例如，RNAi诱导剂可以组合物递送至肺，该组合物实质上由干燥形式(如干粉)的RNAi诱导剂组成，或在水性介质中，该水性介质实质上由水，任选地还包括盐(如NaCl、磷酸盐)、缓冲剂、和/或醇，如作为裸的siRNA或shRNA。

本发明还提供了由肺循环系统循环地递送诱导RNAi的实体的方式。对呼吸道疾病优选的是对循环的转移最少。

口服组合物通常包括惰性稀释剂或可食用的载体。它们可封闭于明胶胶囊或压制为片剂。为了口服治疗给药，活性化合物可并入赋形剂并以片剂、锭剂、或胶囊的形式使用。口服组合物还可使用液态载体而制备用作漱口水，其中液态载体中的该化合物口服应用并漱口，然后吐出或咽下。药学相容的结合剂和/或佐剂可包括在组合物中。片剂、药丸、胶囊、锭剂等可含有以下任何成分或类似特性的化合物：结合剂如微晶纤维素、西黄蓍胶或明胶；赋形剂如淀粉或乳糖、崩解剂如藻酸、Primogel、或玉米淀粉；润滑剂如硬脂酸镁或Sterotes；助流剂如胶体二氧化硅；甜味剂如蔗糖或糖精；或调味剂如薄荷、水杨酸甲酯或橙味料。

系统给药还可以经由跨粘膜或经皮方式。对跨粘膜或经皮给药，对待渗透的屏障合适的渗透剂用于制剂中。这样的渗透剂通常是本领域已知的，并包括例如用于跨粘膜给药的去垢剂、胆盐、和夫西地酸衍生物。跨粘膜给药可通过使用鼻喷雾或栓剂而实现。对经皮给药，如本领域一般所知的，活性化合物可配制为软膏剂、油膏、凝胶、或乳剂。

在一个实施方案中，活性化合物与防止该化合物从机体快速排出的载体一起配制，如控释制剂，包括植入和微囊递送系统。可使用生物可降解的、生物相容的聚合物，如乙烯乙酸乙烯酯、聚酐、聚乙醇酸、胶原、多正酯、和聚乳酸。制备这种制剂的方法对本领域技术人员是显而易见的。材料可购自Alza Corporation和Nova Pharmaceuticals，Inc.脂质体悬浮液(包括靶向于受感染细胞并带有对病毒抗原的单克隆抗体的脂质体)也可用作药学可接受的载体。这些可根据本领域技术人员已知的方法制备，如描述于美国专利No.4,522,811。

尤其有利的是配制吸入、口服或非胃肠组合物于剂量单位形式，以便于给药和剂量的均匀。剂量单位形式是指物理上离散的单位，适于作为用于待处理患者的单位剂量；每个单位含有预先确定量的活性化合物，计算该量以联合所需的药物载体产生期望的治疗效果。用于本发明的剂量单位形式的规格由以下因素确定并直接取决于以下因素：活性化合物的独特特征和要达到的特定治疗效果，以及对治疗个体的这种活性化合物配制领域中固有的限制。

这种化合物的毒性和治疗效力可通过细胞培养物或实验动物中的标准药物步骤来确定，例如确定LD50(半数致死剂量)和ED50(半数治疗有效剂量)。毒性剂量和治疗效力剂量之比是治疗指数，可表示为LD50/ED50。表现大治疗指数的化合物是优选的。尽管可使用表现毒副作用的化合物，但应注意设计靶向这种化合物于受感染组织部位的递送系统，从而使对未感染细胞的可能伤害最小，进而减少副作用。

从细胞培养试验和动物研究获得的数据可用于确定用于人类的剂量范围。这种化合物的剂量优选地在包括ED50并几乎没有或没有毒性的循环浓度范围内。根据所采用的剂型和给药途径，剂量可在此范围内变化。对用于本发明方法的任何化合物，可从细胞培养物或非人类动物试验开始预测治疗有效的剂量。可在动物模型中确定如下剂量：达到包括在细胞培养物中确定的EC50(即，测试化合物达到半最大反应的浓度)的循环血药浓度范围。此信息可用于更准确地确定人类中的有用剂量。可通过例如高效液相色谱法测量血浆中的浓度。

药物组合物可包含在容器、包装、或分配器中，并伴有指导给药的说明。

实施例

实施例1：病毒核蛋白的鉴定

认为高度保守位点是存在于大多数可得的人类流感序列中的位点或序列。变体被识别为人类流感分离物中的19-mer序列，类似于保守的19-mer序列，但仅一个或几个核苷酸改变。这是重要的，因为使用siRNA双链体，RISC(RNA诱导的沉默复合体)仍能起始RNAi活性，siRNA双链体的引导链(反义链)大量互补于靶mRNA序列，但相对于精确互补具有一个或几个核苷酸变化。

组成流感病毒基因组的有八个不同的RNA片段。对每个病毒片段分别进行所有分析。因此，例如仅使用片段#1获得的序列对病毒片段#1进行保守位点的研究。

从流感序列数据库获得八个病毒片段的每一个的甲型流感病毒序列(Macken，C.，Lu，H.，Goodman，J.，& Boykin，L.，“The value of a database insurveillance and vaccine selection.”In Options for the Control of Influenza IV.A.D.M.E.Osterhaus，N.Cox&A.W.Hampson(Eds.)Amsterdam：ElsevierScience，2001，103-106)。筛选列表以除去所有全长序列(带有标签“Complete Cds”的，或具有Complete Cds基因长度＞95％的)，从而不会由于序列平截而不能发现所给靶序列中19-mer片段匹配。进一步筛选序列以消除实验株(除了PR8和WNV，因为测试中用到这些株)，因为实验株很可能具有大量人工诱导的突变；这导致从每种病毒片段中除去2-11序列。最终根据GenBank核苷酸序列数据库(http://www.ncbi.nlm.nih.gov/entrez/query.fcgi？db＝nucleotide)反复核对这些序列以确保所有序列都是当前的。表1列出了符合以上标准并用于随后分析的人类流感序列的Genbank登记号。

表1-1用于该分析的PB2序列(片段1)的Genebank登记号

CY007474，CY002815，CY003391，CY003711，CY002687，CY006202，CY002695，CY002711，CY003383，

CY006674，CY008531，CY002991，CY006434，CY002543，CY003303，CY009003，CY003695，CY006922，

CY002631，CY002535，CY003311，CY006682，CY002575，CY003407，CY003007，CY003399，CY003479，

CY003487，CY006178，CY006370，CY002807，CY006362，CY002703，CY003015，CY003471，CY003031，

CY003295，CY003319，CY663335，CY003840，CY009243，CY001959，CY002679，CY002399，CY006426，

CY006882，CY003023，CY008155，CY002407，CY002623，CY003327，CY006786，CY009179，CY009187，

CY009195，CY009203，CY009211，CY009227，CY009235，CY002655，CY002647，AF258525，AF258524，

DQ249263，AF398866，CY009323，AJ564805，X15283，M38277，CY009291，CY009299，CY008995，CY009371，

CY009347，CY009339，X99035，AF389115，NC_C02023，J02179，DQ208309，CY002359，CY002639，CY003679，

CY002159，CY003703，CY003768，CY006194，CY006418，CY002671，CY006402，CY006410，CY006874，

CY002999，CY006394，CY002367，CY002663，CY006114，CY006754，CY003776，CY003375，CY001687，

AB126635，AB126626，M73524，AY209951，AY209947，AY209948，AY209949，AY209950，AY209945，AY209946，

M91713，AY209942，AY209943，AY2944，AY209941，AY209940，AY209939，M23970，AY209938，AY209937，

AY209936，M81587，M73521，M81575，M81581，AY209934，AY209935，CY002015，CY002079，CY002191，

CY002207，CY002455，CY003647，CY002007，CY002063，CY002463，CY002471，CY006083，CY006091，

CY002495，CY003655，CY006298，CY002271，CY002023，CY002487，CY002727，CY003055，CY002247，

CY002783，CY007802，CY007810，CY007818，CY008347，CY008355，CY008363，CY008371，CY008379，

CY008387，CY008395，CY008403，CY008411，CY008419，CY008427，CY008435，CY008443，CY008451，

CY008563，CY008571，CY008579，CY008587，CY008595，CY008603，CY008611，CY008619，CY008635，

CY008643，CY008651，CY008659，CY009035，CY009043，CY009051，CY006130，CY08627， CY006162，

CY002039，CY002743，CY003063，CY003351，CY006138，CY006154，CY006146，CY002071，CY002199，

CY002921，CY002929，CY002976，CY002983，CY002055，CY002215，CY002231，CY002239，CY002423，

CY002599，CY003039，CY003343，CY006186，CY006378，CY006386，CY000040，CY002255，CY002937，

CY003663，CY002223，CY002961，CY002031，CY000768，CY002945，CY003671，CY006122，CY002953，

CY002969，CY000264，CY002183，CY002263，CY002295，CY008171，CY001036，CY002719，CY002913，

CY003079，CY006099，CY002431，CY002439，CY002447，CY002047，CY008211，CY002799，CY003415，

CY006442，CY007282，CY007290，CY007298，CY007306，CY007314，CY007322，CY007330，CY007346，

CY007354，CY007378，CY007386，CY007394，CY007410，CY007434，CY007442，CY007450，CY007458，

CY007482，CY007490，CY007498，CY007514，CY007538，CY007546，CY007554，CY007562，CY008227，

CY008235，CY008915，CY009259，CY009267，CY009275，CY007650，CY008195，CY000896，CY007338，

CY007506，CY008243，CY007370，CY007586，CY000376，CY002287，CY007362，CY007402，CY007426，

CY007466，CY007522，CY007530，CY007570，CY007578，CY008259，CY007418，CY001236，CY0027791，

CY008251，CY002415，CY002607，CY002615，CY002735，CY002767，CY003047，CY003423，CY008219，

CY008523，CY000568，CY002087，CY002479，CY002511，CY002591，CY002775，CY002351，CY000016，

CY000032，CY000128，CY000136，CY000152，CY000160，CY000176，CY000184，CY000352，CY000384，

CY000519，CY001044，CY001052，CY000956，CY000760，CY001519，CY001719，CY000368，CY000972，

CY000048，CY000064，CY000080，CY000088，CY000104，CY000144，CY000168，CY000255，CY000272，

CY000360，CY000480，CY000512，CY000528，CY000776，CY000784，CY000792，CY000888，CY000916，

CY001095，CY001260，CY001412，CY001543，CY001567，CY001631，CY001639，CY001647，CY001655，

CY002111，CY000096，CY003687，CY000056，CY001028，CY001071，CY001103，CY001060，CY006866,

CY001292，CY006946，CY006930，CY006938，CY006954，CY006962，CY006970，CY006978，CY006986，

CY006994，CY007002，CY007010，CY007018，CY007026，CY007034，CY007050，CY007066，CY007082，

CY007090，CY007098，CY007106，CY007114，CY007122，CY007130，CY007138，CY007146，CY007154，

CY007162，CY007178，CY007186，CY007194，CY007202，CY007218，CY007226，CY007234，CY007250，

CY007266，CY007274，CY008875，CY008883，CY008891，CY008899，CY008907，CY008923，CY009027，

CY009251，CY007258，CY001196，CY008203，CY001380，CY000872，CY000072，CY001119，CY007042，

CY007058，CY007074，CY007210，CY007242，CY007170，CY008547，CY008555，CY000024，CY000200，

CY000908，CY000980，CY001020，CY001212，CY001476，CY001551，CY000880，CY001428，CY000008，

CY000112，CY000964，CY001167，CY001220，CY001228，CY001300，CY001348，CY001468，CY001559，

CY002527，CY000924，CY003135，CY003199，CY003119，CY003151，CY003159，CY003431，CY003784，

CY000232，CY000288，CY000496，CY003103，CY003111，CY003132，CY003143，CY003175，CY003183，

CY003191，CY003207，CY000948，CY000296，CY001735，CY001087，CY001324，CY000120，CY000216，

CY000224，CY000240，CY000248，CY000304，CY000320，CY000336，CY000344，CY000432，CY000440，

CY000448，CY000536，CY000552，CY000560，CY000592，CY000800，CY000940，CY001079，CY001159，

CY001191，CY001244，CY001743，CY001951，CY002135，CY003167，CY003215，CY000424，CY000504，

CY001332，CY001308，CY008323，CY007594，CY007602，CY007610，CY007658，CY007666，CY007674，

CY007682，CY007690，CY007698，CY007706，CY007714，CY007722，CY007730，CY007738，CY007746，

CY007754，CY007762，CY007刀0，CY007778，CY007786，CY007794，CY008291，CY008331，CY008275，

CY008299，CY001444，CY008267，CY001316，CY008283，CY008307，CY008339，CY008315，CY001268，

CY000400，CY000408，CY000416，CY000544，CY000632，CY001111，CY001340，CY001436，CY001135，

CY001204，CY001151，CY000932，CY002823，CY000192，CY000583，CY001175，CY003095，CY003087，

CY000208，CY000280，CY000392，CY000488，CY000576，CY002335，CY000727，CY000312，CY000328，

CY000455，CY003455，CY003463，CY003247，CY003287，CY000616，CY000704，CY000720，CY001004，

CY003832，CY000816，CY003271，CY003279，CY003255，CY003263，CY003816，CY000472，CY000664，

CY000672，CY000712，CY000744，CY000824，CY000840，CY000848，CY000856，CY000988，CY001252，

CY001284，CY001404，CY001527，CY001372，CY003824，CY006666，CY008483，CY008491，CY008507，

CY008763，CY008771，CY008779，CY008787，CY008795，CY008803，CY008811，CY008827，CY008851，

CY008859，CY008867，CY009091，CY009107，CY009123，CY009131，CY009155，CY009163，CY009171，

CY008515，CY008499，CY008755，CY008819，CY008835，CY008843，CY009083，CY009139，CY009147，

CY000696，CY001143，AJ293920，CY001695，CY001879，CY001903，CY001983，CY001999，CY002311，

CY003615，CY003631，CY006067，CY001775，CY001831，CY001847，CY001895，CY001919，CY001991，

CY002303，CY002375，CY003623，CY003639，CY000624，CY000648，CY000736，CY000808，CY001943，

CY003583，CY003591，CY003599，CY001935，CY003231，CY003808，CY003792，CY006906，CY000608，

CY000464，CY000600，CY000680，CY000688，CY000728，CY000832，CY000996，CY001012，CY001127，

CY001583，CY001663，CY001671，CY001751，CY001759，CY001767，CY001783，CY001815，CY001839，

CY001863，CY001871，CY001887，CY001975，CY002119，CY002143，CY002175，CY002319，CY002343，

CY002583，CY001927，CY003239，CY003439，CY003575，CY003607，CY001799，CY002167，CY003223，

CY007642，CY009115，CY006075，CY003800，CY002567，CY001276，CY001703，CY000640，CY000656，

CY000752，CY000864，CY001183，CY001356，CY001420，CY001535，CY001855，CY001911，CY001967，

CY002151，CY001615，CY001711，CY001388，CY001452，CY001460，CY001599，CY001607，CY001623，

CY002519，CY002559，CY001364，CY003447，CY006170，CY003567，CY002391，CY002383，CY001484，

CY001492，CY001500，CY001679，CY001807，CY001823，CY006258，CY006546，CY006290，CY006466，

CY006482，CY006490，CY006498，CY006506，CY006538，CY006554，CY006562，CY006570，CY006578，

CY006586，CY006594，CY006602，CW006610，CY006626，CY006642，CY006778，CY006794，CY006802，

CY006810，CY008187，CY008539，CY008931，CY008947，CY008955，CY008963，CY008971，CY008979，

CY008987，CY006522，CY001791，CY002127，CY001575，CY001511，CY001591，CY002551，AF258841，

AF258842，CY006250，CY006274，CY006266，CY006234，CY006242，CY006282，CY006450，CY006458，

CY006514，CY006530，CY006618，CY006634，CY008939，CY006474，AF037417，AF483602，AF037414，

AF037415，AF037416，CY002279，AF037413，U71133，U71134，U71135，CY006346，CY003759，CY006338，

U71132，CY006354，CY009019，AF037412，CY003719，CY003071，CY008747，M73517，CY003519，CY008731，

CY008739，CY003359，U62543，CY003551，CY002O95，CY002759，CY008723，CY003543，CY003527，CY003511，

CY008459，CY008675，CY008715，CY009075，CY006330，CY008179，CY003751，CY0033727，CY003743，

CY006322，CY006858，CY009059，CY006059，CY006762，CY007634，CY003495，CY006106，CY007626，

CY008475，CY008667，CY006210，CY006898，CY006698，CY006706，CY006714，CY007618，CY006738，

CY006746，CY006770，CY006850，CY006730，CY006842，CY006890，CY008699，CY008707，CY009067，

CY006051，CY003735，CY006914，CY003503，CY006722，CY006826，CY006834，CY003535，CY006818，

CY009011，CY002103，CY003559， M91712， CY002751，CY006314，CY008467，CY008691，CY008683，AY210149，

AY210150，CY002503，CY006226，CY006690，AY210146，AY210147，AY210148，AY210143，AY210144，

AY210145，AJ564804， CY006306，AY210140，AY210141，AY210142，J02140，CY008163，AF348170，AF348171，

CY006218，AY20137，AY210138，AY210139，DQ360837，DQ372598，DQ138181，AY651721，AY651718，

AY651719，AY818126，AB212050，AB212051，AY576380，AY576381，AF2588446，AF036363，AF258837，

AF258838，AF258839，AF258840，AF258843，AF258844，AF258845，AJ404632， AF084261，AF084262，AF084263，

AF115290，AF1115291，AF046093， DQ226172，AF258835，AF258836，AJ404630，AJ404631，AY043030

表1-2用于该分析的PB2序列(片段2)的Genebank登记号

CY007473，CY002542，CY003382，CY002710，CY003390，CY002694，CY002814，CY002686，CY002990，

CY003710，CY008530，CY003694，CY006201，CY006433，CY006921，CY009002，CY003302，CY002630，

CY006673，CY002534，CY003310，CY006681，CY002574，CY006369，CY003478，CY003406，CY003486，

CY002622，CY002702，CY001958，CY003470，CY003030，CY003398，CY002806，CY008154，CY003014，

CY006177，CY006881，CY009242，CY003006，CY003334，CY006361，CY002678，CY003022，CY002398，

CY003839，CY003326，CY006785，CY003318，CY006425，CY002406，CY003294，CY002646，CY002654，

CY009178，CY009186，CY009194，CY009202，CY009210，CY009234，CY009226，AF258526，AF342823，

AF258527，AF398865，CY009322，M25934，AJ564807，M38376，CY009290，CY009298，CY008994，M25932，

CY009370，CY009346，CY009338，X99037，AF389116，NC_002021，J02178，DQ208310，CY002158，CY002638，

CY006193，CY002662，CY002358，CY006393，CY006409，CY006417，CY003702，CY003678， CY006401，

CY006873，CY006753，CY003767，CY002366，CY006113，CY002998，CY002670，CY001686，CY003775，

CY003374，AB126625，AB126634，M25935，AY210025，AY210021，AY210022，AY210023，AY210024，AY210019，

AY210020，AY210016，AY210017，AY210018，AY210015，AY210014，AY210013，M23972，AY210012，AY210011，

AY210010，M25924，M81574，M81580，M81586，AY210008，AY210009，CY002006，CY002014，CY003646，

CY006082，CY006297，CY006090，CY002038，CY002270，CY002462，CY002470，CY003654，CY007801，

CY007809，CY007817，CY008346，CY008354，CY008370，CY008378，CY008386，CY008394，CY008402，

CY008410，CY008418，CY008426，CY0O8434，CY008442，CY008450，CY008562，CY008570，CY008578，

CY008586，CY008602，CY008610，CY008626，CY008650，CY008658，CY009034，CY009042， CY009050，

CY006137，CY008362，CY008594，CY008618，CY008634，CY008642，CY002190，CY002454，CY006129，

CY006153，CY002726，CY006145，CY002022，CY002062，CY002078，CY002486，CY002494，CY002742，

CY002782，CY003062，CY003350，CY006161，CY002206，CY002246，CY003054，CY000039，CY000263，

CY002070，CY002198，CY002238，CY002928，CY002982，CY002214，CY002598，CY002054，CY001035，

CY006377，CY003662，CY006098，CY006385，CY002912，CY002920，CY002952，CY002968，CY002975，

CY002936，CY000767，CY000375，CY002960，CY002718，CY002944，CY003670，CY007465，CY006441，

CY007281，CY007289，CY007297，CY007305，CY007313，CY007321，CY007329，CY007337，CY007345，

CY007353，CY007361，CY007369，CY007377，CY007385，CY007393，CY007401，CY007409，CY007417，

CY007433，CY007441，CY007457，CY007481，CY007489，CY007497，CY007529，CY007537，CY007545，

CY007553，CY007561，CY007649，CY008210，CY008218，CY008226，CY008234，CY008914，CY009258，

CY009266，CY009274，CY001235，CY007425，CY007449，CY007513，CY007569，CY007577，CY007585，

CY008194，CY008242，CY008258，CY002222，CY002230，CY007505，CY007521，CY008250，CY006185，

CY003078，CY006121，CY008170，CY000567，CY000895，CY002182，CY002262，CY002286，CY002294，

CY002422，CY002446，CY002774，CY003038，CY003046，CY003414，CY002086，CY002734，CY002798，

CY008522，CY002254，CY002430，CY002030，CY002046，CY002414，CY002438，CY002478，CY002510，

CY002590，CY002606，CY002614，CY002766，CY003342，CY003422，CY002790，CY000256，CY000007，

CY000015，CY000063，CY000087，CY000103，CY000135，CY000159，CY000167，CY000175，CY000183，

CY000271，CY000367，CY000383，CY000479，CY000511，CY000907，CY001043，CY001051，CY001102，

CY000915，CY000023，CY000031，CY000111，CY000143，CY000151，CY000199，CY000527，CY000759，

CY000783，CY000971，CY001059，CY001070，CY001227，CY001299，CY001411，CY001638，CY001654，

CY002350，CY000359，CY003686，CY000071，CY000047，CY000351，CY000518，CY000791，CY000871，

CY000879，CY001019，CY001118，CY001518，CY001566，CY000095，CY000079，CY007057，CY001027，

CY006865，CY006929，CY006937，CY006945，CY006953，CY006961，CY006969，CY006977，CY006985，

CY006993，CY007001，CY007009，CY007017，CY007025，CY007033，CY007041，CY007049，CY007065，

CY007073，CY007081，CY007089，CY007097，CY007105，CY007113，CY007121，CY007129，CY007137，

CY007145，CY007153，CY007177，CY007185，CY007193，CY007201，CY007209，CY007217，CY007225，

CY007233，CY007241，CY007249，CY007257，CY007265，CY007273，CY008554，CY008874，CY008882，

CY008890，CY008898，CY008906，CY008922，CY009026，CY009250，CY007161，CY007169，CY008202，

CY000887，CY000979，CY001094，CY001291，CY001211，CY001475，CY008546，CY000775，CY000055，

CY000127，CY000923，CY000955，CY000963，CY001166，CY001219，CY001259，CY001347，CY001379，

CY001427，CY001467，CY001550，CY001630，CY001646，CY001718，CY002526，CY001195，CY001558，

CY001542，CY002110，CY000215，CY000223，CY000239，CY000247，CY000439，CY000495，CY000503，

CY000535，CY000947，CY000119，CY000231，CY000343，CY000447，CY000799，CY001086，CY001323，

CY001742，CY003128，CY003134，CY003142，CY003150，CY003158，CY003198，CY003430，CY003110，

CY003102，CY003182，CY003206，CY003783，CY000287，CY003174，CY000295，CY000319，CY000423，

CY000431，CY000543，CY000551，CY000559，CY000591，CY000631，CY001110，CY001150，CY001158，

CY001243，CY001307，CY001339，CY002134，CY000303，CY003166，CY003190，CY003214，CY007721，

CY007593，CY007601，CY007609，CY007673，CY007681，CY007689，CY007697，CY007705，CY007713，

CY007729，CY007737，CY007753，CY007761，CY007769，CY007777，CY007785，CY007793，CY008274，

CY008290，CY008322，CY008330，CY001315，CY008282，CY007657，CY007665，CY007745，CY008266，

CY008306，CY008314，CY008338，CY008298，CY000939，CY003118，CY001435，CY000335，CY000399，

CY000407，CY000415，CY000931，CY001078，CY001134，CY001190，CY001203，CY001267，CY001331，

CY001734，CY001950，CY001443，CY000207，CY000487，CY000582，CY001174，CY002822，CY000327，

CY003094，CY000191，CY000279，CY000391，CY000575，CY001726，CY003086，CY000311，CY002334，

CY000456，CY000471，CY000615，CY000671，CY000719，CY000987，CY001251，CY003246，CY003254，

CY003270，CY003454，CY003462，CY003262，CY003286，CY000663，CY000695，CY000703，CY000711，

CY000743，CY000847，CY001003，CY001283，CY001403，CY000839，CY003815，CY003831，CY006665，

CYO08482，CY008490，CY008498，CY008506，CY008514，CY008762，CY008770，CY008778，CY008786，

CY008794，CY008802，CY008810，CY008826，CY008834，CY008850，CY008858，CY008866，CY009106，

CY009122，CY009130，CY009138，CY009146，CY009154，CY009162，CY000855，CY008754，CY008842，

CY009082，CY009090，CY009170，CY008818，CY003278，CY003823，CY000815，CY000823，CY001142，

CY001371，CY001526，CY000463，CY000599，CY000727，CY002142，CY000647，CY000679，CY000687，

CY001582，CY001662，CY001670，CY001694，CY001750，CY001758，CY001766，CY001774，CY001782，

CY001798，CY001830，CY001846，CY001862，CY001870，CY001878，CY001886，CY001894，CY001902，

CY001918，CY001926，CY001934，CY001974，CY001990，CY001998，CY002166，CY002302，CY003598，

CY003622，CY003230，CY003614，CY006905，CY002582，CY000607，CY000639，CY000655，CY000735，

CY000807，CY000831，CY001126，CY001982，CY002118，CY002318，CY002342，CY003630，CY001942，

CY001011，CY001182，CY001838，CY002310，CY003446，CY003574，CY003606，CY003799，CY003807，

CY006066，CY006074，CY003582，CY003590，CY003791，CY007641，CY009114，CY003222，CY003638，

CY002374，CY001451，CY001459，CY003238，CY003438，CY000623，CY000751，CY000863，CY000995，

CY001275，CY001355，CY001363，CY001387，CY001419，CY001534，CY001598，CY001614，CY001710，

CY001814，CY001854，CY002150，CY002174，CY002518，CY002558，CY002566，CY006169，CY001606，

CY001622，CY001966，CY001702，CY001910，AJ293921，CY001491，CY001499，CY001678，CY001806，

CY001822，CY002382，CY002390，CY003566，CY001590，CY006465，CY005257，CY006289，CY006481，

CY006489，CY006497，CY006505，CY006521，CY006545，CY006553，CY006561，CY006569，CY006577，

CY006585，CY006593，CY006601，CY006609，CY006625，CY006641，CY006777，CY006793，CY006801，

CY006809，CY008186，CY008930，CY008946，CY008954，CY008962，CY008970，CY008978，CY008538，

CY006537，CY008986，CY002550，CY001483，CY001574，CY001790，CY002126，CY001510，AF258822，

AF258823，CY006233，CY006241，CY006249，CY006265，CY006273，CY006281，CY006449，CY006457，

CY006473，CY006513，CY006529，CY006617，CY006633，CY008938，AF037423，AF483601，AF037420，

AF037421，AF037422，CY002278，AF037419，U71129，U71130，U71131，CY006337，CY006345，CY003758，

U71128， CY006353，CY009018，AF037418，CY003718，CY003070，CY008746，M25936，CY003518，CY008730，

CY008738，CY003358，CY003550，CY002094，CY008722，CY002758，CY003510，CY003526，CY003542，

CY008458，CY008674，CY008714，CY009074，CY006329，CY008178，CY003750，CY006857，CY003726，

CY006321，CY003742，CY009058，CY006058，CY006761，CY007633，CY003494，CY006105，CY006209，

CY007625，CY008474，CY008666，CY006897，CY006697，CY006705，CY006713，CY007617，CY006769，

CY006737，CY006745，CY006849，CY006729，CY006841，CY006889，CY008698，CY008706，CY009066，

CY003734，CY006050，CY006913，CY003502，CY006721，CY006825，CY006833，CY009010，CY003534，

CY006817，CY003558，CY002102，CY002750，CY006313，CY008466，CY008690，CY008682，AY2100283，

AY210284，CY006225，CY006689，CY002502，AY210279，AY210280，AY210281，AY210277，AY210278，

AY210282，AJ564806，CY006305，AY210274，AY210275，AY210276，AF348172，AF348173，J02138，CY008162，

CY006217，AY210271，AY210272，AY210273，DQ360838，DQ372597， DQ138163，DQ138164，DQ138165，

AY818129，DQ138159，DQ138160，AY651664，AY651667，AY651665，AY651666，AB212052，AY576392，

AY576393，AF258827，AF036362，AF258818，AF258819，AF258820，AF258821，AF258824，AF258825，AF258826，

AJ404633，AF046094，AF084264，AF084265，AF084266，AF115293，DQ226161，AF258816，AF258817，AJ404634，

AY043029，M74899

表1-3用于该分析的PA序列(片段3)的Genebank登记号

DQ381564，CY007472，CY002541，CY002813，CY003381，CY002629，CY002685，CY002693，CY002709，

CY002989，CY003301，CY003693，CY003709，CY006200，CY006672，CY008529，CY009001，CY006920，

CY006432，CY003389，CY003309，CY002533，CY006680，CY001957，CY002677，CY003477，CY006880，

CY003405，CY003317，CY002573，CY002621，CY002701，CY002805，CY003021，CY003293，CY003325，

CY003333，CY003397，CY003469，CY003485，CY003838，CY006176，CY006368，CY006424，CY006360，

CY003029，CY002397，CY003005，CY003013，CY009241，CY008153，CY006784，CY002405，CY002645，

CY002653，CY009177，CY009185，CY009193，CY009201，CY009209，CY009225，CY09233，AF258519，

AF258518，AF398864，AF398862，CY009321，AJ605762，CY009289，CY009297，CY008993，CY009369，CY009345

CY009337，X99039，AF389117，NC_002022，X17336，DQ208311，CY002157，CY002357，CY002637，CY002365，

CY003677，CY006408，CY006752，CY006416，CY006192，CY006392，CY006872，CY003701，CY006400，

CY003766，CY006112，CY002661，CY002997，CY002669，CY001685，CY003774，CY003373，AB126627，

AB126633，M26079，AY210007，AY210003，AY210004，AY210005，AY210006，AY210001，AY210002，AY209998

AY209999，AY210000，AY209997，AY209996，AY209995，M23974，AY209994，AY209993，AY209992，M26078，

M81573，M81579，M81585，AY209990，AY209991，CY002061， CY002269，CY002469，CY003645，CY02005，

CY002037，CY002461，CY002205，CY003653，CY006081，CY006089，CY006296，CY002725，CY002013，

CY002189，CY002077，CY002741，CY008657，CY002435，CY008649，CY007800，CY008345，CY008353，

CY008361，CY008369，CY008377，CY008385，CY008393，CY008401，CY008417，CY008425，CY008433，

CY008441，CY008449，CY008577，CY008585，CY008633，CY008641，CY009033，CY009041，CY009049，

CY008569，CY008609，CY007808，CY007816，CY008561，CY008593，CY008601，CY008617，CY008625，

CY002453，CY008409，CY006160，CY002493，CY003061，CY002021，CY002245，CY006128，CY003349，

CY006136，CY002781，CY003053，CY006144，CY006152，CY002181，CY002069，CY002197，CY002213，

CY002229，CY002237，CY002261，CY002597，CY002911，CY002919，CY002981，CY002053，CY002429，

CY002974，CY000038，CY000374，CY000766，CY001234，CY002045，CY002253，CY002413，CY002445，

CY002927，CY002951，CY002967，CY003661，CY006184，CY006376，CY006384，CY000262，CY002935，

CY000894，CY002943，CY001034，CY002421，CY002613，CY002959，CY003341，CY003669，CY008913，

CY003037，CY006440，CY007280，CY007296，CY007304，CY007312，CY007320，CY007328，CY007336，

CY007344，CY007352，CY007368，CY007376，CY007384，CY007392，CY007408，CY007432，CY007456，

CY007480，CY007512，CY007544，CY007648，CY008193，CY008225，CY009257，CY009265，CY009273，

CY007416，CY007584，CY008169，CY007424，CY007496，CY008249，CY007360，CY007520，CY002437，

CY002765，CY002029，CY002717，CY007464，CY007488，CY007536，CY007560，CY008241，CY002733，

CY007288，CY007440，CY007448，CY007528，CY007552，CY007568，CY007576，CY008209，CY008217，

CY008233，CY008257，CY006097，CY007400，CY003077，CY007504，CY000566，CY002789，CY002085，

CY002221，CY002285，CY002477，CY002589，CY002605，CY003413，CY003421，CY002293，CY008521，

CY002509，CY002773，CY002797，CY003045，CY006120，CY000030，CY000006，CY000022，CY000350，

CY001093，CY001549，CY001629，CY001645，CY001653，CY002349，CY000078，CY000758，CY001165，

CY000014，CY000046，CY000062，CY000070，CY000086，CY000094，CY000102，CY000126，CY000134，

CY000150，CY000158，CY000166，CY000174，CY000182，CY000198，CY000254，CY000270，CY000358，

CY000366，CY000382，CY000478，CY000510，CY000517，CY000526，CY000782，CY000790，CY000870，

CY000878，CY000906，CY000914，CY000954，CY000970，CY001018，CY001042，CY001050，CY001058，

CY001069，CY001117，CY001218，CY001226，CY001258，CY001290，CY001298，CY001346，CY001378，

CY001410，CY001517，CY001541，CY000110，CY001026，CY000142，CY001565，CY001637，CY000886，

CY001557，CY001717，CY003685，CY001466，CY006952，CY006864，CY006944，CY007200，CY006928，

CY006936，CY006960，CY006968，CY006976，CY006984，CY006992，CY007000，CY007008，CY007016，

CY007024，CY007032，CY007040，CY007048，CY007056，CY007064，CY007072，CY007080，CY007088，

CY007096，CY007104，CY007112，CY007120，CY007128，CY007136，CY007144，CY007152，CY007168，

CY007184，CY007192，CY007216，CY007224，CY007240，CY007264，CY007272，CY008201，CY008553，

CY008873，CY008881，CY008889，CY008897，CY008905，CY008921，CY009025，CY009249，CY007232，

CY007256，CY002525，CY007208，CY007248，CY007160，CY007176，CY000978，CY001210，CY001474，

CY008545，CY002109，CY000054，CY000774，CY000922，CY001101，CY000962，CY001194，CY001426，

CY000238，CY000246，CY000550，CY000798，CY000946，CY001338，CY001733，CY003133，CY003149，

CY003429，CY003782，CY003157，CY003173，CY003197，CY003205，CY000118，CY000214，CY000222，

CY000230，CY000294，CY000302，CY000334，CY000342，CY000422，CY000430，CY000438，CY000446，

CY000494，CY000502，CY000534，CY000558，CY000590，CY000630，CY000938，CY001077，CY001157，

CY001242，CY001306，CY001322，CY001434，CY001741，CY001949，CY002133，CY003101，CY003109，

CY003126，CY003141，CY003189，CY001314，CY003181，CY001133，CY001109，CY001189，CY000318，

CY000542，CY000930，CY001149，CY007592，CY007600，CY007608，CY007656，CY007664，CY007672，

CY007680，CY007688，CY007696，CY007704，CY007744，CY007760，CY007768，CY007776，CY007784，

CY007792，CY008273，CY008289，CY008321，CY007752，CY008329，CY007728，CY008305，CY000414，

CY007720，CY007712，CY007736，CY008337，CYO08265，CY008281，CY001266，CY001330，CY008297，

CY008313，CY000286，CY000398，CY001085，CY000406，CY003213，CY003165，CY001202，CY001442，

CY003117，CY001725，CY000190，CY000278，CY000390，CY000486，CY000574，CY000581，CY002821，

CY003093，CY000326，CY001173，CY003085，CY002333，CY000310，CY000206，CY003261，CY003453，

CY003245，CY000454，CY000470，CY000614，CY000670，CY000694，CY000702，CY000710，CY000718，

CY000742，CY000814，CY000822，CY000846，CY000854，CY000986，CY001002，CY001250，CY001282，

CY001370，CY003285，CY000662，CY003253，CY003269，CY003461，CY000838，CY001525，CY001402，

CY003830，CY008481，CY008801，CY009105，CY009137，CY006664，CY008489，CY008505，CY008513，

CY008785，CY008793，CY008809，CY008849，CY008865，CY009129，CY009145，CY009153，CY009169，

CY008497，CY008769，CY003814，CY008761，CY008753，CY008857，CY009121，CY009161，CY008777，

CY008817，CY008825，CY008833，CY008841，CY009081，CY009089，CY003277，CY003822，CY001141，

CY001773，CY001829，CY001845，CY001861，CY001869，CY001877，CY001885，CY001917，CY001933，

CY001973，CY002117，CY002173，CY003237，CY003613，CY003621，CY001581，CY001925，CY001981，

CY001989，CY001997，CY002141，CY003573，CY003605，CY000462，CY000598，CY000606，CY000622，

CY000646，CY000654，CY000678，CY000686，CY000726，CY000734，CY000806，CY000830，CY000994，

CY001125，CY001181，CY001354，CY001362，CY001458，CY001693，CY001701，CY001709，CY001749，

CY001757，CY001765，CY001781，CY001797，CY001813，CY001837，CY001901，CY001909，CY001941，

CY002165，CY002301，CY002565，CY002581，CY003229，CY003581，CY003589，CY003597，CY003637，

CY006065，CY006073，CY006904，CY000638，CY001893，CY003790，CY002341，CY003629，CY001661，

AJ293922，CY002309，CY001010，CY001274，CY001669，CY007640，CY009113，CY003437，CY002517，

CY003445，CY001853，CY000862，CY000750，CY001533，CY002557，CY002373，CY001597，CY002149，

CY002317，CY001386，CY001418，CY001605，CY001613，CY001621，CY001965，CY003806，CY001450，

CY003798，CY003221，CY006168，CY001805，CY001821，CY002389，CY001498，CY003565，CY001490，

CY001789，CY002381，CY001509，CY001677，CY006288，CY006464，CY008185，CY006256，CY006552，

CY006576，CY006584，CY008945，CY008961，CY006480，CY006488，CY006496，CY006504，CY006520，

CY006536，CY006544，CY006568，CY006592，CY006624，CY006640，CY006776，CY006792，CY006808，

CY008929，CY008953，CY008969，CY008977，CY008985，CY006600，CY006608，CY008537，CY006800，

CY001482，CY006560，CY002125，CY001573，CY001589，CY002549，AF257197，AF257198，CY006264，

CY006472，CY006280，CY006232，CY006248，CY006272，CY006456，CY006528，CY006632，CY008937，

CY006240，CY006448，CY006616，CY006512，AF037429，AF483603，AF037426，AF037427，AF037428，CY002277，

AF037425，U71137，U71138，U71139，CY006344，CY003757，CY006336，U71136，CY006352，CY009017，

AF037424，CY003717，CY008745，CY003069，CY003357，CY003517，CY008729，CY008737，CY003549，

CY002093，CY008721，CY002757，CY003509，CY003525，CY003541，CY009073，CY008673，CY008713，

CY008457，CY006328，CY008177，CY003749，CY003741，CY006856，CY009057，CY003725，CY006320，

CY006057，CY006760，CY007632，CY006104，CY003493，CY006208，CY007624，CY008473，CY008665，

CY006896，CY006696，CY006704，CY006712，CY007616，CY006736，CY006744，CY006768，CY006848，

CY006840，CY008697，CY008705，CY006728，CY006888，CY009065，CY006049，CY003733，CY006912，

CY003501，CY006720，CY006824，CY006832，CY009009，CY003533，CY006816，CY002101，CY002749，

CY003557，CY008681，CY006312，CY008465，CY008689，AY210205，AY210206，CY002501，CY006688，

CY006224，AY210202，AY210203，AY210204，AY210199，AY210200，AY210201，AJ605763，CY006304，

AY210196，AY210197，AY210198，AF348175，J02139，CY008161，AF348174，CY006216，AY210193，AY210194，

AY210195，DQ360839，DQ138184，DQ138185，DQ138186，DQ138187，DQ138188，DQ372596，DQ099791，

DQ099792，AY818132，AY651610，AY651611，AY651613，AY651612，AB212053，AY576404，AY576405，

AF257202，AF257193，AF257194，AF257195，AF257196，AF257199，AF257200，AF257201，AJ289874，AJ291402，

AF046095，AF084267，AF084268，AF084269，AF084270，AF115294，AF115295，AF257191，AF257192，AJ404637，

AY043028

表1-4用于该分析的HA序列(片段4)的Genebank登记号

L20113，U38242，DQ265706，CY007467，CY002624，CY002808，CY002688，CY003384，CY002984，CY002680，

CY003376，CY003704，CY006195，CY006667，CY06915，CY002536，CY003688，CY002704，CY003296，

CY008996，CY006427，CY008524，DQ249260，CY003304，CY002528，CY006675，AY299507，AY297155，

AY297156，AY299497，AY299509，AY299505，AY299495，AY299496，AY299500，AY299502，AY299504，

AY299508，AY299499，AY299498，AY299506，AY297157，AY299501，AY299503，AY297154，AY299494，

AJ457877，AJ517815，AJ457930，AY971011，CY003472，CY006363，CY003833，CY002568，CY002672，CY002392

CY003024，CY001952，CY002616，CY002800，CY003016，CY003288，CY003312，CY003400，CY003464，

CY003480，CY006171，CY006355，CY003320，CY009236，CY008148，CY006419，CY002696，CY006779，

CY006875，CY002400，CY003008，CY003328，CY003392，CY003000，AY682833，AJ517814，AJ457871，AJ457873

AJ457872，AJ457886，AJ457865，AJ457870，AJ457888，AY971009，AJ457867，AJ457866，AJ457863，AJ457869

AJ457881，AY971006，AJ457868，AY971008，AY063229，AY971010，AY063228，CY002640，CY009172，

CY009180，CY009188，CY009196，CY009204，CY009220，CY009228，CY002648，AJ457902，AJ457887，AJ457904，

AJ457862，AY971007，AB043499，AB043498，AY029287，AY029288，AY029289，AY029290，AY029291，

AY029292，AY971004，AY971003，AY289929，AJ344014，AF534030，AF534031，AF534038，AJ457905，AB043496

AB043497，AF268312，AF268313，AF386775，AF386776，AF386777，AF386778，AF386780，AF386781，AF386782，

AF386779，AF387491，AF342821，AJ457885，AJ457892，AJ457894，AJ457898，AB043495，AB043500，AF534025，

AF534026，AF534027，AJ457891，AJ457895，A1457897，AB043494，AY282756，AY282758，AF026153，AF026154，

AF026155，AF026156，AF026157，AF026158，AF026159，AF026160，AJ457906，AJ457896，AB043492，AB043493，

AF131993，AF131994，AF131995，AF386773，AF386774，AY289928，AY289930，AF398878，AJ344022，AF398875，

AJ457907，AJ457899，AJ457900，AB043491，ISDNX127，U53162，U53163，AJ457901，AB043490，AF055426，

AY289927，CY009316，L24362，Z54289，Z54288，AJ57908，AB043489，L19017，L19549，L33480，L33481，L33482

L33743，L33744，L33745，L33746，L33747，L33748，L33749，L33750，L33751，L33758，L33780，L19013，L19018，

L19020，L19022，L19026，L19027，L20106，L20107，L20108，L201 09，L20110，L20111，L201 12，L20116，L20117，

D13573，D13574，AB043488，D31949，L19016，L19028，L33756，Z54287，X59778，L19011，L19014，L19015，

L19019，L19021，L19023，L19024，L19025，L33487，L33752，L33753，L33754，L33755，M33748，AB043487，

L33485，L33486，D00841，X17224，D00406，D00407，L19012，L33483，Z54286，S62154，L33490，L33491，L33492，

L33493，AJ289702，X17221，M59324，M59325，M59326，M59327，M59328，L33489，X00031，X00030，M38353，

X86654，X86655，X86656，X86657，X00028，L33484，L33488，L33757，CY009284，CY09292，X00027，K01331，

CY008988，AB043486，CY009364，AB043485，AB043484，CY009340，AB043483，AB043482，AB043480，

AB3043481，CY009332，AB043479，U02085，AF494249，AF494250，AF494247，AF494248，AF494251，AF494246，

NC_002017，AF389118，J02144，J02176，U08903，U08904，AF117241，AF116575，AF116576，U37727，CY002360，

CY003672，CY003696，CY003761，CY002992，CY002352，CY002632，CY002656，CY002152，CY006107，

CY006387，CY006867，CY02664，CY006187，CY006395，CY006411，CY006403，CY006747，CY00368，

CY003769，CY001680，AB126622，AB126630，AJ457909，AJ457911，AJ457878，AJ457861，AJ457875，AJ457910，

AY684125，AF503473，AF503474，AF503476，AF503477， AF503478，AF503479，AF503480，AF503481，AF503482，

AF503483，AF503485，AF5003486，AF5003484，AF503475，D10163，L19005，L19006，L19008，L11125，L11133，

AY209988，AY209989，AY209978，AY209979，AY209980，AY209981，AY209982，AY209983，AY209984，

AY209985，AY209986，AY209987，AY209974，AY209975，AY209976，AY209977，D13579，D13580，AY209970，

AY209971，AY209972，AY209973，L11126，AY209967，AY209968，AY209969，AY209963，AY209964，AY209965

AY209966，AY209959，AY209960，AY209961，AY209962，AY209955，AY209956，AY209957，AY209958，

AY209954，AF270721，L11134，AF270725，AF270726，AF270727，AF270723，AF270724，AB056699，J02127，

L11142，L20406，L20407，L20408，L20409，L20410，AY643085，AY643087，AY643086，AY209952，AY209953，

AF270716，AF270717，A1270718，AF270719，AF270720，AF270722，AF270728，DQ265709，DQ265716，CY002000

CY002056，CY002184，CY003640，CY006076，CY006084，CY002072，CY002448，CY002456，CY006291，

CY002008，CY002032，CY002200，CY002464，CY003648，CY003344，CY002240，CY002488，CY002736，

CY002264，CY006123，CY003048，CY006139，CY006155，CY008628，CY008652，CY007795，CY007803，

CY007811，CY008340，CY008348，CY008356，CY008372，CY008380，CY008388，CY008396，CY008404，

CY008412，CY008420，CY008428，CY008436，CY008444，CY008564，CY008572，CY008580，CY008636，

CY008644，CY009028，CY009036，CY009044，CY003056，CY008620，CY002776，CY008556，CY008588，

CY008596，CY008604，CY008612，CY006131，CY002480，CY008364，CY006147，CY002720，CY002016，

DQ265707，DQ265708，DQ265710，DQ265711，DQ265712，DQ265713，DQ265714，DQ265715，DQ265717，

CY000257，CY002024，CY002064，CY002192，CY002592，DQ249261，DQ249262，CY000889，CY002040，

CY002176，CY002208，CY002216，CY002224，CY002232，CY002904，CY000033，CY000761，CY001229，

CY002048，CY002416，CY002600，CY006371，CY000369，CY002906，CY002914，CY002922，CY002946，

CY002930，CY006115，CY006179，CY003040，CY003664，CY006379，CY008164，CY002954，CY001029，

CY002408，CY002424，CY003032，CY002712，CY002760，CY002905，CY002938，CY003072，CY003656，

CY008516，CY002432，CY002256，CY002962，CY002248，CY002440，CY002584，CY007283，CY007459，

CY002728，CY002792，CY002288，CY006092，CY007387，CY003416，CY006435，CY007275，CY007291，

CY007299，CY007307，CY007315，CY007323，CY007331，CY007347，CY007371，CY007379，CY007427，

CY007435，CY007443，CY007451，CY007475，CY007483，CY007491，CY007507，CY007531，CY007539，

CY007547，CY007555，CY008188，CY008204，CY008212，CY008220，CY008228，CY008908，CY009252，

CY009260，CY009268，CY007419，CY007563，CY007643，CY008244，CY002280，CY007339，CY007355，

CY007363，CY007403，CY007499，CY007515，CY007571，CY007579，CY008236，CY008252，CY007395，

CY007523，CY007411，CY000561，CY002768，CY002784，CY002080，CY003336，CY002472，CY002504，

CY003408，CY002608，AY947474，AY963789，AY963790，AY963791，AY963792，AY963793，AY945263，

AY945264，AY945265，AY945266，AY945267，AY945268，AY945269，AY945270，AY945271，AY945272，

AY945273，AY945274，AY945275，AY945276，AY945277，AY945278，AY945279，AY945280，AY945281，

AY945282，AY945283，AY945284，AY945285，AY945286，AY945287，AY945288，CY000001，CY000065，

CY000097，CY000137，CY000161，CY000177，CY000265，CY000345，CY000361，CY000901，CY001064，

CY001632，DQ249259，CY000073，CY000089，CY000377，CY001405，CY000009，CY000025，CY000057，

CY000081，CY000121，CY000129，CY000145，CY000153，CY000169，CY000193，CY000353，CY000505，

CY000513，CY000753，CY000777，CY000909，CY000965，CY001013，CY001021，CY001045，CY001112，

CY001213，CY001512，CY000017，DQ089636，CY001285，DQ086160，CY000041，CY000105，CY000249，

CY000473，CY000785，CY000957，CY000973，CY001037，CY001053，CY001061，CY001221，CY002344，

DQ089635，CY000881，CY000949，CY001648，DQ089637，DQ089638，DQ089639，CY003680，CY001088，

CY000873，CY001293，CY007163，DQ086161，CY009020，CY001560，CY007003，CY007083，CY006859，

CY006923，CY006931，CY006939，CY006947，CY006955，CY006963，CY006971，CY006979，CY006987，

CY006995，CY007011，CY007019，CY007035，CY007043，CY007051，CY007059，CY007067，CY007091，

CY007099，CY007107，CY007115，CY007123，CY007131，CY007139，CY007147，CY007155，CY007187，

CY007195，CY007267，CY008876，CY008884，CY008892，CY008900，CY008916，CY009244，CY007179，

CY007235，CY008196，CY008548，CY008868，CY007027，CY001160，CY001421，CY001469，CY001544，

CY001640，CY002104，CY002520，CY007243，CY007075，CY007171，CY007203，CY007211，CY007219，

CY007227，CY007251，CY007259，CY001341，CY001712，CY008540，CY000049，CY000521，CY000865，

CY000917，CY001096，CY001205，CY001253，CY001461，CY001536，CY001552，CY001624，DQ089634，

CY000769，CY001373，DQ086159，AY531033，AY531039，AY531040，AY531041，AY531042，AY531043，

AY531044，AY531045，AY531046，AY531047，AY531048，AY531049，AY531050，AY531051，AY531052，

AY531053，AY531054，AY531055，AY531056，AY531057，AY531058，AY531059，AY531060，AY531061，

DQ059385，DQ086157，DQ086158，AY963783，AY963784，AY963785，AY963786，AY963787，AY963788，

AY963796，CY000113，CY000233，CY000241，CY000585，CY000793，CY000941，CY001080，CY003120，

CY003123，CY003136，CY003200，CY003777，CY000537，CY003104，CY003144，CY000209，CY000217，

CY000225，CY000281，CY000337，CY000425，CY000433，CY000441，CY000489，CY000497，CY000529，

CY001728，CY001736，CY003096，CY003192，CY001317，CY001333，CY003176，CY003112，CY003168，

CY003424，CY003152，CY000933，CY000289，CY000329，CY000545，CY000553，CY001152，CY001197，

CY001325，CY002128，CY003160，CY003184，CY003208，CY001301，CY001072，CY000313，CY001144，

DQ227423，CY007587，CY007595，CY007603，CY007651，CY007659，CY007667，CY007675，CY007683，

CY007691，CY007699，CY007707，CY007715，CY007723，CY007731，CY007739，CY007747，CY007755，

CY007763，CY007771，CY007779，CY007787，CY008284，CY008324，CY008332，CY001309，CY000625，

CY001437，CY008268，CY008276，CY008292，CY001944，CY008260，CY008316，CY000297，CY000393，

CY000401，CY000409，CY000417，CY000925，CY001104，CY001128，CY001184，CY001237，CY001261，

CY001429，CY008308，CY008300，DQ227431，DQ227424，DQ227425，DQ227426，DQ227427，AY589647，

AY589648，AY589649，AY589650，AY589651，AY589652，AY589653，AY589654，AY589655，AY589656，

AY589657，AY589658，AY589659，AY589660，AY589661，DQ227429，AY884276，AY884277，AY884278，

AY884279，AY884280，AY884281，AY884282，AY884283，AY884284，DQ227430，DQ227428，AY661030，

AY661031，AY947476，AY377129，AY968039，AY968037，AY968040，AY968038，AY968041，CY000584，

CY000481，CY000273，CY001168，CY002816，CY003088，CY001720，CY000185，CY000569，CY003080，

CY000385，CY000201，CY000305，CY000321，CY002328，AY661022，AY661023，AY661024，AY968029，

AY968030，AY968031，CY000609，CY003256，CY000465，CY000657，CY000665，CY000705，CY000713，

CY000737，CY000317，CY000849，CY000981，CY001245，CY001520，CY000997，CY001365，CY003240，

CY003448，CY003456，CY003825，CY003264，CY000449，CY000841，CY001277，CY001397，CY003248，

CY003272，CY003280，CY003809，CY003817，CY008844，CY000697，CY008492，CY000833，CY009140，

CY006659，CY008476，CY008484，CY008500，CY008508，CY008764，CY008780，CY008788，CY008796，

CY008804，CY008852，CY008860，CY009100，CY009116，CY009124，CY009132，CY009148，CY009156，

CY009164，CY008748，CY008756，CY008772，CY008820，CY008828，CY008836，CY009084，CY008812，

CY009076，CY000689，CY000809，CY001136，AY661021，AY968024，AY968023，AF382319，AF382320，

AF382321，AF382322，AF382323，AF382324，AF382325，AF382326，AF382327，AF382328，AY035588，AY035589，

AY035590，AY035591，AY035592，CY000593，CY001656，CY001688，CY001752，CY001768，CY001776，

CY001824，CY001832，CY001840，CY001856，CY001864，CY001872，CY001880，CY001888，CY001896，

CY001920，CY001928，CY001976，CY001984，CY002136，CY003608，CY003624，CY000601，CY001760，

CY001912，CY001992，CY002160，CY000457，CY000641，CY000649，CY000681，CY000721，CY000729，

CY000801，CY000825，CY001176，CY001576，CY001904，CY002296，CY002560，CY002576，CY003224，

CY003632，CY003592，CY001968，CY003232，CY000633，CY002168，CY001120，CY001413，CY001792，

CY001936，CY002112，CY002312，CY002336，CY002368，CY001744，CY003568，CY003584，CY003785，

CY003801，CY006060，CY006068，CY003576，CY003440，CY003600，CY000617，CY001453，CY003616，

CY000673，CY006899，CY001848，CY003793，CY001808，CY001005，CY001269，CY007635，CY009108，

CY003432，CY002552，CY000745，CY001664，CY000857，CY000989，CY001349，CY001357，CY001381，

CY001445，CY001528，CY001592，CY001600，CY001608，CY001616，CY002304，CY002512，CY003216，

CY001696，CY006163，CY001704，CY001960，CY002144，AY531035，AJ293926，AY963782，AY963794，

AY963795，AF315566，AF315564，AF315565，AY661019，AY661026，AY968020，AY968019，AY968021，

AB019355，AB019356，AF382318，AY032978，CY001816，CY003560，CY002376，CY001485，CY001493，

CY001784，CY001800，CY002384，CY001584，CY006283，CY008980，CY006515，CY008180，CY006251，

CY006459，CY006475，CY006483，CY006491，CY006499，CY006531，CY006539，CY006547，CY006555，

CY006563，CY006571，CY006579，CY006587，CY006595，CY006603，CY006619，CY006635，CY006771，

CY006787，CY006795，CY008940，CY008948，CY008956，CY008964，CY008972，CY001504，CY002544，

CY006803，CY008532，CY008924，CY002120，CY001672，CY001477，CY001568，AY271794，AF316818，

AF316820，AF316821，AF316819，AF315560，AF315563，AF315571，AF316817，AF15561，AY661206，AY661207，

AY661208，AY661209，AF315559，AF315562，CY006227，CY006243，CY006467，CY006507，CY006451，

CY006235，CY006259，CY006275，CY006443，CY006523，CY006611，CY006627，CY008932，CY006267，

AF363502，AF363503，AF363504，AJ311466，AF315567，AF315569，AF315570，AF315568，AY661201，AY661202，

AY661203，AY661205，AY661210，AF017272，AY661193，AY661194，AY661195，AY661197，AY661198，

AY661199，AY661200，AF131996，AF131997，AF131998，AF017270，AF017271，AB019354，AB019357，

CY002272，AF534013，AF534014，AF534015，AF534016，AF534017，AF534018，AY661181，AY661182，AY661183，

AY661185，AY661186，AY661187，AY661188，AY661189，AY661190，AY661191，AY661192，AY661196，U48444，

U48445，U48447，U65553，U65554，U65555，U65556，U65557，U65558，U65559，U65560，CY006331，CY006339，

CY003752，AY661020，AY661176，AY661175，AY661177，AY661178，AY661179，AY661204，AY661180，Z4403，

Z46404，Z46405，Z46407，Z46408，AB043708，U48439，U48440，U48441，U48442，U48443，U48446，U65552，

CY006347，CY009012，AY661131，AY661132，AY661133，AY661139，AY661140，AY661141，AY661142，

AY661143，AY661144，AY661145，AY661146，AY661147，AY661148，AY661149，AY661150，AY661151，

AY661152，AY661153，AY661154，AY661155，AY661156，AY661157，AY661158，AY661159，AY661161，

AY661162，AY661163，AY661165，AY661166，AY661167，AY661168，AY661169，AY661170，AY661171，

AY661172，AY661173，AY661174，AY661211，D30669，D30668，Z46393，Z46394，Z46395，Z46396，Z46397，

Z46398，Z46399，Z46400，Z46401，Z46402，Z46406，Z46411，Z46412，Z46413，Z46414，Z46415，Z46416，Z46417，

AB043707，AY661160，AY661164，CY003712，U26830，AY661080，AY661082，AY661083，AY661084，AY661085，

AY661086，AY661087，AY661088，AY661089，AY661090，AY661091，AY661092，AY661093，AY661094，

AY661095，AY661096，AY661097，AY661108，AY661109，AY661110，A6Y61111，AY661112，AY661113，

AY661114，AY661115，AY661116，AY661117，AY661118，AY661120，AY661121，AY661122，AY661123，

AY661124，AY661126，AY661127，AY661128，AY661129，AY661130，AY661134，AY661135，AY661136，

AY661137，AY661138，D30665，D30664，Z46392，Z46410，AB043706，AY661125，AY661081，D30663，AY661075，

AY661076，AY661077，AY661078，AY661079，AY661098，AY661099，AY661100，AY661101，AY661102，

AY661103，AY661104，AY661105，AY661106，AY661107，AY661119，D30662，AB043705，D49967，CY003064，

CY008740，AY661073，D49966，AY661069，AY661070，AY661072，AY661074，Z46409，D49965，U97740，

AY661059，AY661066，D49961，AY661029，AY661057，AY661058，AY661060，AY661061，AY661062，AY661063，

AY661064，AY661065，AY661067，AY661068，AY661071，X75800，D49962，Z46391，D4963，D49960，D49964，

AJ252129，AJ252131，CY003512，CY008724，CY008732，CY003352，AY61054，AY661055，AY661056，AF204238，

CY003544，M57644，D49959，CY002088，CY002752，CY008716，AY661053，M21648， M57632，CY003520，

CY003536，CY003504，CY008668，CY008708，CY009068，CY008452，AY661049，AY661050，AY661051，

AY661052，AF405211，M57631，CY006323，CY008172，CY003744，CY006851，CY003736，CY006315，CY003720，

CY009052，AY661016，AF201845，AF201846，AF405209，AF405210，AF405207，CY006052，CY006755，U08858，

U08859，U08905，AY661015，AY661025，AY661048，AF233691，CY007627，AY661014，AF201844，AF405206，

M57630，CY006043，CY003488，CY008468，CY006203，CY008660，CY006891，CY007619，AY661046，AY661047，

AF405212，J02092，AF201843，CY006691，CY006699，CY006707，CY007611，X05907，CY006763，CY006731，

CY006739，CY006843，AY661011，AY661012，AY661013，AY661045，AF450246，CY006723，CY006835，

CY006883，CY008692，CY008700，CY009060，AY661006，AY661007，AY661008，AY661010，AY661044，

AY661009，V01086，CY006044，CY003728，AY661043，AY661028，CY006907，CY003496，CY006715，CY006819，

CY006827，AY661042，AY661005，AY661017，AY661018，AY661027，CY003528，CY009004，CY006811，

AY661002，AY661003，AY661004，AF201842，M54895，CY002744，CY002096，CY003552，CY006307，CY008460，

CY008676，CY008684，AY661041，V01089，AY660999，AY661000，AY661001，AF201875，J02132，CY002496，

CY006683，CY006219，AY660996，AY660997，AY660998，AY660995，AY660994，CY006299，AY660992，

AY660993，AY661040，J02135，V01085，V01103，M55059，CY008156，AF348176，AF348177，AF348178，

AF348179，CY006211，AY660991，AY661038，AY661039，AF201874，AB239125，DQ372591，AY555153，

AY555150，AJ867074，AY818135，AY679514，AY651334，AY651335，AY651333，AY651336，AJ715872，

AY720950，AB212054，AY575869，AY575870，AF102676，AF028709，AF046088，AF046096，AF046097，AF046098，

AF036356，AF084279，AF084280，AF084281，AF084532，AF102671，AF102672，AF102673，AF102674，AF102675，

AF102677，AF102678，AF102679，AF102680，AF102681，AF102682，AF028020，DQ226106，AJ404626，AJ404627，

AY043019，AY043015，AY043017，AY043018

表1-5用于该分析的NP序列(片段5)的Genebank登记号

CY007470，CY002811，CY002683，CY002691，CY003379，CY003691，CY003707，CY002707，CY003299，

CY002539，CY002627，CY006430，CY006918，CY008999，CY006198，CY003387，CY006670，CY008527，

CY002987，CY002531，CY006678，CY003307，CY001955，CY002571，CY003403，CY003475，CY006174，

CY003011，CY003395，CY003291，CY002803，CY003836，CY003315，CY003467，CY002675，CY003003，

CY003027，CY006878，CY003483，CY002699，CY003323，CY008151，CY006366，CY009239，CY002395，

CY002403，CY003019，CY006782，CY003331，CY006358，CY002619，CY006422，CY002651，CY002643，

CY009175，CY009183，CY009199，CY009223，CY009231，CY009191，CY009207，AF258516，AF342819，

AF258517，DQ249264，AF398867，L24394，CY009319，Z54292，M63755，M76602，M76610，Z54291，Z54290，

AJ628066，M59329，M59330，M59331，M59332，M59333，M59334，X51972，D00599，D00600，D00603，CY009287，

CY009295，M63754，M76605，M76606，M76604，CY008991，CY009367，M63751，CY009343，D00601，CY009335，

M63750，U02086，M63749，AF389119，M30746，AY744935，CY002355，CY002659，CY0006750，CY003675，

CY006390，CY002363，CY002155，CY006414，CY006406，CY006190，CY002667，CY003699，CY006110，

CY006870，CY003764，CY002995，CY006398，CY002635，CY001683，CY003772，CY003371，AB126624，

AB126632，M63753，AY210103，AY210104，AY210093，AY210094，AY210095，AY210096，AY210097，AY210098，

AY210099， AY210100，AY210101，AY210102，AY210089，AY210090，AY210091，AY210092，AY210085，

AY210086，AY210087，AY210088，AY210082，AY210084，AY210081，AY210083，AY210077， AY210078，

AY210079，AY210080，AY210075，AY210076，M23976，AY210074，AY210072，AY210073，AY210070，AY210071，

M81571，M81577，M81583，M63752，AY210066，AY210067，AY210068，AY210069，CY02003，CY002011，

CY002467，CY006079，CY002059，CY006087，CY003643，CY003651，CY002451，CY002723，CY002459，

CY002019，CY002075，CY002491，CY006294，CY003051，CY002203，CY002267，CY003059，CY006142，

CY002779，CY008359，CY007798，CY007806，CY007814，CY008343，CY008351，CY008367，CY008375，

CY008383，CY008391，CY008399，CY008407，CY008415，CY008423，CY008431，CY008439，CY008447，

CY008567，CY008575，CY008583，CY008591，CY008615，CY008631，CY008639，CY008647，CY008655，

CY009031，CY009039，CY009047，CY002187，CY006150，CY008559，CY008599，CY008607，CY008623，

CY002483，CY006134，CY006126，CY002739，CY006158，CY002035，CY002243，CY003347，CY000036，

CY000372，CY000564，CY000764，CY001032，CY001232，CY002051，CY002067，CY002043，CY002195，

CY002227，CY002595，CY002925，CY002933，CY002949，CY002979，CY000260，CY006382，CY002771，

CY002941，CY002179，CY002235，CY002251，CY002259，CY002611，CY002731，CY002909，CY002715，

CY002763，CY002957，CY002965，CY002972，CY003075，CY006118，CY008167，CY002917，CY000892，

CY002027，CY007446，CY002219，CY003659，CY003667，CY006095，CY006374，CY006438，CY002787，

CY003043，CY003339，CY003411，CY008519，CY002427，CY006182，CY007326，CY008911，CY009255，

CY007454，CY008207，CY008223，CY007374，CY007478，CY007558，CY009263，CY002587，CY007278，

CY007286，CY007294，CY007302，CY007310，CY007334，CY007350，CY007382，CY007390，CY007430，

CY007438，CY007462，CY007486，CY007494，CY007518，CY007534，CY007542，CY007550，CY007582，

CY008215，CY008231，CY002211，CY007318，CY007342，CY007358，CY007366，CY007398，CY007406，

CY007414，CY007502，CY007526，CY007566，CY007574，CY007646，CY008191，CY008239，CY008247，

CY008255，CY009271，CY002435，CY007422，CY002507，CY002411，CY002419，CY003419，CY002795，

CY007510，CY002475，CY002291，CY002443，CY002603，CY003035，CY002283，CY002083，CY000780，

CY000756，CY000004，CY000020，CY000044，CY000060，CY000068，CY000076，CY000084，CY000092，

CY000100，CY000132，CY000148，CY000156，CY000164，CY000172，CY000180，CY000196，CY000268

CY000348，CY000356，CY000364，CY000380，CY000476，CY000508，CY000520，CY000788，CY000904，

CY000912，CY000920，CY000960，CY000968，CY001024，CY001040，CY001048，CY001056，CY001067，

CY001091，CY001099，CY001115，CY001208，CY001216，CY001224，CY001296，CY001408，CY001635，

CY001651，CY002347，CY000028，CY000524，CY001016，CY000012，CY000052，CY000252，CY001192，

CY000108，CY001288，CY001715，CY000140，CY001515，CY001627，CY002523，CY001424，CY003683，

CY007142，CY000124，CY000772，CY001344，CY006862，CY000952，CY008551，CY000976，CY007118，

CY007006，CY007070，CY007102，CY007198，CY006926，CY006934，CY006942，CY006966，CY007022，

CY007054，CY007110，CY007270，CY006958，CY007014，CY007046，CY007062，CY007078，CY007086，

CY007094，CY007126，CY007166，CY007174，CY008543，CY009023，CY006950，CY006974，CY006982，

CY006990，CY006998，CY007134，CY007150，CY007190，CY007262，CY008895，CY008903，CY009247，

CY001563，CY007030，CY007182，CY007206，CY007214，CY007222，CY007230，CY007238，CY007246，

CY007254，CY008199，CY008879，CY008887，CY008919，CY001163，CY001555，CY007158，CY001472，

CY008871，CY002107，CY000868，CY001376，CY000876，CY000884，CY001256，CY001464，CY001539，

CY001547，CY001643，CY007038，CY000116，CY000212，CY000220，CY000228，CY000236，CY000244，

CY000292，CY000300，CY000316，CY000332，CY000340，CY000420，CY000428，CY000436，CY000444，

CY000492，CY000500，CY000532，CY000548，CY000556，CY000588，CY000628，CY000796，CY000944，

CY001083，CY001147，CY001155，CY001320，CY001336，CY001731，CY001739，CY002131，CY003099，

CY003115，CY003124，CY003130，CY003155，CY003203，CY003427，CY003179，CY003195，CY000284，

CY001131，CY001312，CY003107，CY003780，CY001240，CY003187，CY003147，CY003139，CY000540，

CY000396，CY000404，CY000928，CY001075，CY001107，CY001187，CY001200，CY001432，CY003171，

CY001440，CY003163，CY003211，CY007774，CY001947，CY007694，CY001264，CY007742，CY007750，

CY007758，CY007766，CY007590，CY007598，CY007606，CY007654，CY007662，CY007670，CY007678，

CY007686，CY007702，CY007710，CY007718，CY007726，CY007734，CY007782，CY007790，CY008287，

CY008327，CY008263，CY008271，CY008279，CY008303，CY008311，CY008319，CY008335，CY001328，

CY000936，CY001304，CY000412，CY008295，CY001171，CY000188，CY000204，CY000276，CY000324，

CY000388，CY000484，CY000572，CY000579，CY002331，CY002819，CY003091，CY001723，CY003083，

CY000308，CY000452，CY000468，CY000612，CY000660，CY000668，CY000692，CY000700，CY000708，

CY000716，CY000740，CY000836，CY000852，CY001248，CY001400，CY001523，CY000844，CY003459，

CY003259，CY003243，CY000984，CY001000，CY000820，CY000812，CY001280，CY003451，CY003251，

CY003267，CY003275，CY003283，CY003820，CY003828，CY001368，CY003812，CY009167，CY006662，

CY008783，CY008791，CY008799，CY008807，CY008815，CY008855，CY009103，CY009119，CY009127，

CY009135，CY009159，CY008479，CY008487，CY008503，CY008511，CY008823，CY008831，CY008847，

CY008863，CY009087，CY009143，CY009151，CY008495，CY008751，CY008759，CY008767，CY008775，

CY009079，CY008839，CY001139，CY000604，CY001579，CY001763，CY000460，CY000636，CY000644，

CY000652，CY000676，CY000732，CY001123，CY001416，CY001667，CY001691，CY001747，CY001755，

CY001771，CY001811，CY001875，CY001883，CY001891，CY001899，CY001915，CY001923，CY001931，

CY001979，CY001987，CY002163，CY002371，CY003579，CY003595，CY003611，CY003619，AJ458276，

CY000596，CY000724，CY000804，CY002115，CY000684，CY001995，CY002579，AJ293924，CY003571，

CY003627，CY003635，CY003603，CY006071，CY001595，CY001659，CY001699，CY001779，CY001827，

CY001843，CY001859，CY001867，CY002139，CY002339，CY001851，CY000620，CY000828，CY000860，

CY000992，CY002299，CY002315，CY002563，CY006166，CY001352，CY001907，CY001939，CY001971，

CY001272，CY001619，CY003219，CY003435，CY003788，CY003796，CY003804，CY003227，CY003587，

CY003443，CY006063，CY006902，CY002171，CY001707，CY001795，CY001835，CY009111，CY007638，

CY001179，CY002555，CY003235，CY000748，CY001008，CY001603，CY001963，CY002515，CY001456，

CY002147，CY001611，CY001384，CY001360，CY001448，CY002307，CY001531，CY001496，CY001587，

CY001803，CY002379，CY002387，CY003563，AB019359，AB019360，CY001488，CY001507，CY001819，

CY001571，CY001675，CY002123，CY006254，CY006574，CY006774，CY008943，CY006462，CY006494，

CY006550，CY006558，CY006638，CY006286，CY006478，CY006486，CY006502，CY006518，CY006534，

CY006542，CY006566，CY006582，CY006590，CY006598，CY006606，CY006622，CY006798，CY006806，

CY008183，CY008535，CY008927，CY008951，CY008959，CY008967，CY008975，CY008983，CY006790，

CY001787，CY001480，CY002547，AF255748，AF255749，AJ458277，CY006454，CY006614，CY006630，CY008935，

CY006230，CY006238，CY006246，CY006262，CY006270，CY006278，CY006446，CY006470，CY006510，

CY006526，AF038259，AF483604，AF038256，AF038257，AF038258，AB019358，AB019361，CY002275，AF038255，

U71145，U71146，U71147，CY006342，CY003755，CY006334，U71144，AY936880，CY006350，CY009015，

AF038254，CY003715，L07357，CY008743，CY003067，L07356，L07355，L07353，L07354，L07372，L07373，L07374，

L07369，L07370，CY003515，CY003355，CY008727，CY008735，L07368，L07371，L0366，L07367，CY003547，

L07365，CY002091，CY008719，CY002755，CY003523，CY003539，L07364，CY003507， CY008455，CY008671，

CY008711，CY009071，L07362，L07363，CY006326，CY008175，CY003747，M22577，CY00373 9，CY006318，

CY003723，CY006854，CY009055，CY006055，CY006758，CY007630，L07352，L07360，L07361，CY003491，

CY006102，CY008663，CY008471，CY006206，CY006894，CY007622，L07350，L07351，CY006694，CY006702，

CY006710，CY007614，D00602，L07359，CY006742，CY006734，CY006766，CY006846，L07349，CY006726，

CY006838，CY006886，CY008695，CY008703，CY009063，AF072545，CY006047，L07358，CY003731，CY003499，

CY006910，CY006822，CY006718，CY006830，L07346，L07347，CY003531，CY009007，CY006814，CY002099，

D00051，L07345，CY003555，CY002747，CY006310，CY008463，CY008687，CY008679，L07342，L07343，L07344，

AY210234，AY210235，AY210236，AY210237，AY210238，CY006222，CY002499，L07341，CY006686，AY210230，

AY210231，AY210232，AY210233，AY210226，AY210227，AY210228，AY210229，CY006302，AY210221，

AY210222，AY210223，AY210224，AY210225，J02137，CY008159，AF348180，AF348183，CY006214，L07340，

AF348181，AY210207，AY210208，AY210209，AY210210，AY210211，AY210212，AY210213，AY210214，

AY210215，AY210216，AY210217，AY210218，AY210219，AY210220，AF348182，AY93688 1，DQ372594，

DQ360840，DQ099781，DQ099783，DQ099782，DQ099780，DQ099779，DQ099775，AJ867076，AY818138，

DQ099776，AY651498，AY651499，AY651501，AY651500，AB212055，AY575905，AY575906，AF255753，

AF036359，AF255744，AF255745，AF255746，AF255747，AF255750，AF255751，AF255752，AJ289873，AJ291400，

AJ291401，AF028710，AF046092，AF084276，AF084277，AF084278，AF115284，AF115285，DQ226139，AF255742，

AF255743，AJ289872，AJ289871，AY043026

表1-6用于该分析的NA序列(片段6)的Genebank登记号

CY007469，CY002538，CY002626，CY002682，CY002690，CY002706，CY002810，CY002986，CY003298，

CY003378，CY003386，CY003690，CY003706，CY006197，CY006429，CY006669，CY00691 7，CY008526，

CY008998，AJ518100，AJ518101，AY297140，AY297141，AY297142，AY297143，AY297144，AY297145，

AY297146，AY297147，AY297148，AY297149，AY297150，AY297151，AY297152，AY297153，AY310407，

AY310408，AY310409，AY310410，AY310411，AY310412，CY002530，CY003306，CY006677，DQ249254，

DQ249256，DQ249258，AJ518091，CY001954，CY002394，CY002402，CY002570，CY002618，CY002674，

CY002698，CY002802，CY003002，CY003010，CY003018，CY003026，CY003290，CY003314，CY003322，

CY003330，CY003394，CY003402，CY003466，CY003474，CY003482，CY003835，CY006173，CY006357，

CY006365，CY006421，CY006781，CY006877，CY008150，CY009238，AJ518093，AJ518095，CY002642，CY002650，

CY009174，CY009182，CY009190，CY009198，CY009206，CY009222，CY009230，AJ518092，DQ249252，

AF342820，AJ518098，AJ518096，AJ518099，AY904335，AF398868，AF398869，AF398872，AJ518097，AJ518104，

U53166，D31945，CY009318，D31950，D31944，D31948，AJ006954，X15281，AF494254，M38335，CY009286，

CY009294，K02018，M38309，AF250363，M27970，CY008990，CY009366，CY009342，CY009334，AF250357，

AF494253，AY122327，DQ345546，Y14193，AF250365，AF494252，AY122326，AF389120，NC_002018，J02177，

L25815，L25816，L25817，AF250356，CY002154，CY002354，CY002362，CY002634，CY002658，CY002666，

CY002994，CY003674，CY003698，CY003763，CY006109，CY006189，CY006389，CY006397，CY006405，

CY006413，CY006749，CY006869，AB126623，AB126631，AJ457943，AJ489848，AJ489849，AJ489850，AJ489851，

CY001682，CY003370，CY003771，AF503463，AF503464，AF503465，AF503466，AF503467，AF503468，AF503469，

AF503470，AF503471，AF503472，AJ457944，AJ489846，AJ489847，D10164，AB101673，AB124657，AY209932，

AY209933，AY209922，AY209923，AY209924，AY209925，AY209926，AY209927，AY209928，AY209929，

AY209930，AY209931，K01393，AY209918，AY209919，AY209920，AY209921，AY209914，AY209915，AY209916，

AY209917，AB101672，AB124656，AY209912，AY209913，AY209910，AY209911，AY209906，AY209907，

AY209908，AY209909，AY209904，AY209905，AB124655，AY209903，AY209901，AY209902，AY209899，

AY209900，AB101671，AB124653，AB124654，AY209895，AY209896，AY209897，AY209898，AY643088，

AY643089，J02156，L37329，L37330，L37331，CY002002，CY002010，CY002018，CY002034，CY002058，

CY002074，CY002186，CY002202，CY002242，CY002266，CY002450，CY002458，CY002466，CY002482，

CY002490，CY002722，CY002738，CY002778，CY003050，CY003058，CY003346，CY003642，CY003650，

CY006078，CY006086，CY006125，CY006133，CY006141，CY006149，CY006157，CY006293，CY007797，

CY007805，CY007813，CY008342，CY008350，CY008358，CY008366，CY008374，CY008382，CY008390，

CY008398，CY008406，CY008414，CY008422，CY008430，CY008438，CY008446，CY008558，CY008566，

CY008574，CY008582，CY008590，CY008598，CY008606，CY008614，CY008622，CY008630，CY008638，

CY008646，CY008654，CY009030，CY009038，CY009046，CY000035，CY000259，CY000371，CY000563，

CY000763，CY000891，CY001031，CY001231，CY002026，CY002042，CY002050，CY002066，CY002082，

CY002178，CY002194，CY002210，CY002218，CY002226，CY002234，CY002250，CY002258，CY002282，

CY002290，CY002410，CY002418，CY002426，CY002434，CY002442，CY002474，CY002506，CY002586，

CY002594，CY002602，CY002610，CY002714，CY002730，CY002762，CY002770，CY002786，CY002794，

CY002908，CY002916，CY002924，CY002932，CY002940，CY002948，CY002956，CY002964，CY002971，

CY002978，CY003034，CY003042，CY003074，CY003338，CY003410，CY003418，CY003658，CY003666，

CY006094，CY006117，CY006181，CY006373，CY006381，CY006437，CY007277，CY007285，CY007293，

CY007301，CY007309，CY007317，CY007325，CY007333，CY007341，CY007349，CY007357，CY007365，

CY007373，CY007381，CY007389，CY007397，CY007405，CY007413，CY007421，CY007429，CY007437，

CY007445，CY007453，CY007461，CY007477，CY007485，CY007493，CY007501，CY007509，CY007517，

CY007525，CY007533，CY007541，CY007549，CY007557，CY007565，CY007573，CY007581，CY007645，

CY008166，CY008190，CY008206，CY008214，CY008222，CY008230，CY008238，CY008246，CY008254，

CY008518，CY008910，CY009254，CY009262，CY009270，DQ249255，D0249257，AY531006，AY531007，

AY531008，AY531009，AY531010，AY531011，AY531012，AY531013，AY531014，AY531015，AY531016，

AY531017，AY531018，AY531019，AY531020，AY531021，AY531022，AY531023，AY531024，AY531025，

AY531026，AY531027，AY531028，AY531034，CY000003，CY000011，CY000019，CY000027，CY000043，

CY000051，CY000059，CY000067，CY000075，CY000083，CY000091，CY000099，CY000107，CY000123，

CY000131，CY000139，CY000147，CY000155，CY000163，CY000171，CY000179，CY000195，CY000251，

CY000267，CY000347，CY000355，CY000363，CY000379，CY000475，CY000507，CY000515，CY000523，

CY000755，CY000771，CY000779，CY000787，CY000867，CY000875，CY000883，CY000903，CY000911，

CY000919，CY000951，CY000959，CY000967，CY000975，CY001015，CY001023，CY001039，CY001047，

CY001055，CY001063，CY001066，CY001090，CY001098，CY001114，CY001162，CY001207，CY001215，

CY001223，CY001255，CY001287，CY001295，CY001343，CY001375，CY001407，CY001423，CY001463，

CY001471，CY001514，CY001538，CY001546，CY001554，CY001562，CY001626，CY001634，CY001642，

CY001650，CY001714，CY002106，CY002346，CY002522，CY003682，CY006861，CY006925，CY006933，

CY006941，CY006949，CY006957，CY006965，CY006973，CY006981，CY006989，CY006997，CY007005，

CY007013，CY007021，CY007029，CY007037，CY007045，CY007053，CY007061，CY007069，CY007077，

CY007085，CY007093，CY007101，CY007109，CY007117，CY007125，CY007133，CY007141，CY007149，

CY007157，CY007165，CY007173，CY007181，CY007189，CY007197，CY007205，CY007213，CY007221，

CY007229，CY007237，CY007245，CY007253，CY007261，CY007269，CY008198，CY008542，CY008550，

CY008870，CY008878，CY008886，CY008894，CY008902，CY008918，CY009022，CY009246，DQ059384，

DQ090706，DQ090707，DQ090708，DQ090709，DQ090710，DQ091199，AY589662，AY589663，AY589664，

AY589665，AY589666，AY589667，AY589668，AY589669，AY589670，AY589671，AY589672，AY589673，

AY589674，AY589675，AY589676，CY000115，CY000211，CY000219，CY000227，CY000235，CY000243，

CY000283，CY000291，CY000299，CY000315，CY000331，CY000339，CY000395，CY000403，CY000411，

CY000419，CY000427，CY000435，CY000443，CY000491，CY000499，CY000531，CY000539，CY000547，

CY000555，CY000587，CY000627，CY000795，CY000927，CY000935，CY000943，CY001074，CY001082，

CY001106，CY001130，CY001146，CY001154，CY001186，CY001199，CY001239，CY001263，CY001303，

CY001311，CY001319，CY001327，CY001335，CY001431，CY001439，CY001730，CY001738，CY001946，

CY002130，CY003098，CY003106，CY003114，CY003122，CY003129，CY003138，CY003146，CY003154，

CY003162，CY003170，CY003178，CY003186，CY003194，CY003202，CY003210，CY003426，CY003779，

CY007589，CY007597，CY007605，CY007653，CY007661，CY007669，CY007677，CY07685，CY007693，

CY007701，CY007709，CY007717，CY007725，CY007733，CY007741，CY007749，CY007757，CY007765，

CY007773，CY007781，CY007789，CY008262，CY008270，CY008278，CY008286，CY008294，CY008302，

CY008310，CY008318，CY008326，CY008334，DQ227446，U42776，AJ457958，AJ457959，AJ457960，AJ457961，

CY000187，CY000203，CY000275，CY000307，CY000323，CY000387，CY000483，CY000571，CY000578，

CY001170，CY001722，CY002330，CY002818，CY003082，CY003090，DQ249253，AJ307599，AJ307600，AJ307601，

AJ307602，AJ307603，AJ307604，AJ307605，AJ307606，AJ307607，AJ307608，AJ307609，AJ307610，AJ307611，

AJ307612，AJ307613，AJ307614，AJ307615，AJ307616，AJ307617，AJ307618，AJ307619，AJ307620，AJ307621，

AJ307622，AJ307623，AJ307624，AJ307625，AJ307626，AJ307627，AJ307628，AJ307629，AJ457933，AJ457934，

AJ457956，AJ457957，AJ457962，AJ457963，CY000451，CY000467，CY000611，CY000659，CY000667，CY000691，

CY000699，CY000707，CY000715，CY000739，CY000811，CY000819，CY000835，CY000843，CY000851，

CY000983，CY000999，CY001138，CY001247，CY001279，CY001367，CY001399，CY001522，CY003242，

CY003250，CY003258，CY003266，CY003274，CY003282，CY003450，CY003458，CY003811，CY003819，

CY003827，CY006661，CY008478，CY008486，CY008494，CY008502，CY008510，CY008750，CY008758，

CY008766，CY008774，CY008782，CY008790，CY008798，CY008806，CY008814，CY008822，CY008830，

CY008838，CY008846，CY008854，CY008862，CY009078，CY009086，CY009102，CY009118，CY009126，

CY009134，CY009142，CY009150，CY009158，CY009166，AF316808，AF316810，AF382329，AF382330，AF382331，

AF382332，AF386761，AF386762，AF386763，AF386764，AF534001，AJ293923，AJ457931，AJ457935，AJ457936，

AJ457937，AJ457938，AJ457964，AJ457965，AJ457966，AY531036，CY000459，CY000595，CY000603，CY000619，

CY000635，CY000643，CY000651，CY000675，CY000683，CY000723，CY000731，CY000747，CY000803，

CY000827，CY000859，CY000991，CY001007，CY001122，CY001178，CY001271，CY001351，CY001359，

CY001383，CY001415，CY001447，CY001455，CY001530，CY001578，CY001594，CY001602，CY001610，

CY001618，CY001658，CY001666，CY001690，CY001698，CY001706，CY001746，CY001754，CY001762，

CY001770，CY001778，CY001794，CY001810，CY001826，CY001834，CY001842，CY001850，CY001858，

CY001866，CY001874，CY001882，CY001890，CY001898，CY001906，CY001914，CY001922，CY001930，

CY001938，CY001962，CY001970，CY001978，CY001986，CY001994，CY002114，CY002138，CY002146，

CY002162，CY002170，CY002298，CY002306，CY002314，CY002338，CY002370，CY002514，CY002554，

CY002562，CY002578，CY003218，CY003226，CY003234，CY003434，CY003442，CY003570，CY003578，

CY003586，CY003594，CY003602，CY003610，CY003618，CY003626，CY003634，CY003787，CY003795，

CY003803，CY006062，CY006070，CY006165，CY006901，CY007637，CY009110，AF316805，AF316815，

AF316816，AF533730，AF533731，AF533732，AF533733，AF533734，AF533735，AF533736，AF533737，AF533738，

AF533739，AF533740，AF533741，AF533742，AF533743，AF533744，AF533745，AF533746，AF533747，AF533748，

AF533749，AF533750，AJ316063，AJ457932，AJ457939，AJ457940，AJ457941，AY271795，CY001479，C001487，

CY001495，CY001506，CY001570，CY001586，CY001674，CY001786，CY001802，CY001818，CY002122，

CY002378，CY002386，CY002546，CY003562，CY006253，CY006285，CY006461，CY006477，CY006485，

CY006493，CY006501，CY006517，CY006533，CY006541，CY006549，CY006557，CY006565，CY006573，

CY006581，CY006589，CY006597，CY006605，CY006621，CY006637，CY006773，CY006789，CY006797，

CY006805，CY008182，CY008534，CY008926，CY008942，CY008950，CY008958，CY008966，CY008974，

CY008982，AF038264，AF330819，AF533999，AF534000，AJ291403，CY006229，CY006237，CY006245，CY006261，

CY006269，CY006277，CY006445，CY006453，CY006469，CY006509，CY006525，CY006613，CY006629，

CY008934，AF038262，AF038263，AF038265，AF533995，AF533996，AF533997，AF533998，AJ457942，AF038261，

AF533989，AF533990，AF533991，AF533992，AF533993，AF533994，AJ457945，CY002274，U51245，U51246，

U51247，U71141，U71142，U71143，AJ457946，CY003754，CY006333，CY006341，U43422，U43423，U43424，

U43425，U43426，U71140，AF038260，CY006349，CY009014，U42777，U42778，U42779，U42780，U43417，U43418，

U43419，U43420，U43421，CY003714，U42770，U42771，U42772， U42773，U42774，U42775，U43427，U42637，

CY003066，CY008742，U42636， U42635，CY003354，CY0035 14，CY008726，CY008734，U42634，CY003546，

U42633，CY002090，CY002754，CY008718，CY003506，CY003522，CY003538，CY008454，CY008670，CY008710，

CY009070，U42632，CY003746，CY006325，CY008174，CY003722，CY003738，CY006317，CY006853，CY009054，

AB224664，CY006054，CY006757，CY007629，CY003490，CY006101，CY006205，CY006893，CY007621，

CY008470，CY008662，K01150，CY006693，CY006701，CY006709，CY007613，AB124662，AB124663，CY006733，

CY006741，CY006765，CY006845，AB124661，CY006725，CY006837，CY006885，CY008694，CY008702，

CY009062，CY003730，CY006046，CY003498，CY006717，CY006821，CY006829，CY006909，AB124660，

CY003530，CY006813，CY009006，AB124659，AY210132，AY210133，AY210134，AY210135，AY210136，

CY002098，CY002746，CY003554，CY006309，CY008462，CY008678，CY008686，J02168，AB101675，AY210128，

AY210129，AY210130，AY210131，CY002498，CY006221，CY006685，U42631，AY210124，AY210125，AY210126，

AY210127，AY210119，AY210120，AY210121，AY210122，AY210123，CY006301，AB101674，AB124658，

AF348184，AF348185，AF348186，AF348187，AY210105，AY210106，AY210107，AY210108，AY210109，

AY210110，AY210111，AY210112，AY210113，AY210114，AY210115，AY210116，AY210117，AY210118，

CY006213，CY008158，J02136，U42630，AB239126，AY555151，AB212056，AY575881，AF028708，AF036357，

DQ226128，AJ404628，AJ404629，AY043024

表1-7用于该分析的MP序列(片段7)的Genebank登记号

AJ298948，X59240，DQ299489，CY007468，CY002985，CY002537，CY002625，CY002681，CY002705，CY002809，

CY003297，CY003385，CY003689，CY008525，CY003377，CY008997，CY002689，CY003705，CY06196，

CY006668，CY006916，CY006428，DQ249267，CY002529，CY006676，CY003305，CY001953，CY002569，

CY003025，CY003473，CY006780，CY006876，CY002393，CY002401，CY002617，CY002673，CY002697，

CY002801，CY003009，CY003017，CY003289，CY003313，CY003321，CY003465，CY003481，CY003834，

CY006356，CY006364，CY006420，CY008149，CY003329，CY003401，CY003393，CY006172，CY003001，

CY009237，CY002649，CY002641，CY009173，CY009181，CY009189，CY009197，CY009229，CY009205，

CY009221，AF258523，AF342818，AF258522，DQ249265，AF398876，U53168，U53169，CY009317，M63521，

AJ298947，M54941，X53029，CY009285，CY009293，CY008989，CY009365，CY009341，CY009333，X08091，

U02084，AF389121，NC_002016，L25814，L25818，M19374，M23920，X08088，X08089，AY130766，CY002353，

CY002361，CY006388，CY002993，CY002665，CY002657，CY006868，CY002153，CY002633，CY003673，

CY003697，CY003762，CY006188，CY006404，CY006748，CY006396，CY006412，CY006108，CY001681，

CY003770，AB126629，AB126637，CY003369，AF231358，AF231359，M63531，AY210065，AY210055，AY210056，

AY210057，AY210058，AY210059，AY210060，AY210061，AY210062，AY210063，AY210064，AY210051，

AY210052，AY210053，AY210054，AY210047，AY210048，AY210049，AY210050，AY210044，AY210045，

AY210046，AY210041，AY210042，AY210043，AY210037，AY210038，AY210039，AY210040，AY210035，

AY210036，M23978， AY210032，AY210033，AY210034，AY210030，AY210031，M81570， M81576，M81582，

AY210026，AY210027，AY210028，AY210029，X08093，CY002009，CY002033，CY002057，CY002073，CY002185，

CY002201，CY002457，CY002777，CY003049，CY006077，CY006085，CY006132，CY006140，CY006148，

CY006156，CY006292，CY002001，CY002241，CY002449，CY002721，CY003345，CY002017，CY002265，

CY002465，CY002489，CY002737，CY003649，CY003641，CY002481，CY003057，CY006124，CY007796，

CY008405，CY009029，CY007804，CY007812，CY008365，CY008373，CY009045，CY008557，CY008349，

CY008357，CY008605，CY008341，CY008381，CY008389，CY008397，CY008413，CY008421，CY008429，

CY008437，CY008445，CY008573，CY008581，CY008589，CY008597，CY008613，CY008621，CY008629，

CY008637，CY008645，CY009037，CY008565，CY008653，CY002065，CY002081，CY002177，CY002217，

CY002225，CY002233，CY002249，CY002281，CY002409，CY002417，CY002585，CY002601，CY002713，

CY002907，CY002915，CY002931，CY002939，CY002947，CY002955，CY002963，CY002970，CY002977，

CY003041，CY003665，CY006372，DQ249268，CY002425，CY002433，CY002505，CY002729，CY003033，

CY000034，CY000258，CY000370，CY000562，CY000762，CY000890，CY001030，CY001230，CY002025，

CY002041，CY002049，CY002209，CY002257，CY002289，CY002441，CY002473，CY002593，CY002609，

CY002769，CY002923，CY003409，CY003657，CY006180，CY002193，CY002785，CY006116，CY008517，

CY006380，CY008165，CY002761，CY002793，CY003073，CY003337，CY003417，CY007292，CY007388，

CY007508，CY006436，CY007300，CY007308，CY007380，CY007436，CY007444，CY007476，CY007492，

CY007556，CY006093，CY007276，CY007332，CY007348，CY007372，CY007404，CY007452，CY007460，

CY007484，CY007532，CY007548，CY007564，CY007580，CY008205，CY008213，CY009261，CY007364，

CY008221，CY007356，CY007644，CY009253，CY007284，CY007324，CY007412，CY007420，CY007428，

CY007524，CY007540，CY007572，CY008229，CY008245，CY008253，CY008909，CY007316，CY007340，

CY008189，CY009269，CY007500，CY008237，CY007396，CY007516，CY001633，CY003681，DQ098266，

D0098267，CY000194，CY000002，CY000010，CY000018，CY000026，CY000042，CY000050，CY000058，

CY000066，CY000074，CY000082，CY000090，CY000098，CY000106，CY000122，CY000130，CY000138，

CY000146，CY000154，CY000162，CY000170，CYY00178，CY000250，CY000266，CY000346，CY000354，

CY000362，CY000378，CY000474，CY000506，CY000514，CY000522，CY000754，CY000770，CY000778，

CY000786，CY000866，CY000874，CY000882，CY000902，CY000910，CY000950，CY000958，CY000966，

CY000974，CY001014，CY001022，CY001038，CY001046，CY001054，CY001062，CY001065，CY001089，

CY001097，CY001113，CY001161，CY001206，CY001214，CY001222，CY001254，CY001286，CY001294，

CY001374，CY001406，CY001462，CY001470，CY001513，CY001545，CY001553，CY001561，CY001625，

CY001641，CY001649，CY001713，CY002345，CY002521，CY002105，CY001537，DQ098269，DQ100422，

DQ100423，DQ100424，CY001342，CY001422，CY006972，CY006988，CY007036，CY007140，CY007268，

CY000918，CY006924，CY006932，CY006940，CY006956，CY006964，CY006980，CY006996，CY007004，

CY007012，CY007044，CY007052，CY007060，CY007076，CY007084，CY007092，CY007100，CY0007116，

CY007124，CY007132，CY007188，CY006948，CY007020，CY007068，CY007108，CY007148，CY007156，

CY007164，CY007172，CY007180，CY007204，CY007220，CY007228，CY007236，CY007244，CY007252，

CY007260，CY008197，CY009245，CY006860，CY007196，CY008541，CY008549，CY008885，CY008893，

CY008901，CY008917，CY009021，CY008869，CY008877，CY007212，CY007028，CY000234，CY000242，

CY000546，CY000942，CY001334，CY003127，CY003145，CY003153，CY003201，CY003778，CY000538，

CY000554，CY000794，CY001198，CY003121，CY003177，CY003193，CY000114，CY000210，CY000218，

CY000226，CY000282，CY000290，CY000298，CY000314，CY000330，CY000338，CY000394，CY000402，

CY000410，CY000418，CY000426，CY000434，CY000442，CY000490，CY000498，CY000530，CY000626，

CY000926，CY000934，CY001073，CY001081，CY001105，CY001129，CY001145，CY001153，CY001185，

CY001238，CY001302，CY001310，CY001318，CY001326，CY001729，CY001737，CY001945，CY002129，

CY003097，CY003105，CY003161，CY003169，CY003185，CY003425，CY003209，CY001262，CY000586，

CY001438，CY003137，CY007652，CY007764，CY007780，CY001430，CY007588，CY007596，CY007604，

CY007668，CY007676，CY007684，CY007740，CY007748，CY007772，CY007788，CY003113，CY007660，

CY007692，CY007700，CY007708，CY007716，CY007724，CY007732，CY007756，CY008277，CY008301，

CY008269，CY008293，CY008333，CY008261，CY008285，CY008309，CY008317，CY008325，CY002817，

DQ249266，CY000186，CY000202，CY000274，CY000322，CY000386，CY000482，CY000570，CY000577，

CY001169，CY001721，CY002329，CY003081，CY003089，CY000306，CY001398，CY003249，CY003257，

CY003449，CY003457，CY003265，CY003273，CY000450，CY000466，CY000610，CY000658，CY000666，

CY000690，CY000698，CY000706，CY000714，CY000738，CY000810，CY000818，CY000834，CY000842，

CY000850，CY000982，CY000998，CY001246，CY001278，CY001366，CY003810，CY003826，CY003281，

CY006660，CY001137，CY003241，CY001521，CY008501，CY008509，CY009101，CY009149，CY003818，

CY008837，CY008477，CY009085，CY009117，CY009133，CY009141，CY009165，CY008485，CY008749，

CY008757，CY008773，CY008781，CY008789，CY008797，CY008805，CY008813，CY008821，CY008829，

CY008845，CY008853，CY008861，CY009077，CY009125，CY009157，CY008493，CY008765，AJ293925，

AY386765，AF386766，AF386767，AF386768，AF386770，AF386771，AF386772，CY001529，CY001617，CY001665，

CY001809，CY001873，CY001881，CY002297，CY002305，CY002337，CY003433，CY003569，CY003577，

CY003585，CY003609，CY003617，CY006061，CY006900，CY001897，CY001977，CY001985，CY002169，

CY003625，CY003786，CY000458，CY000594，CY000602，CY000618，CY000634，CY000642，CY000650，

CY000674，CY000682，CY000722，CY000730，CY000802，CY000826，CY000858，CY000990，CY001006，

CY001121，CY001177，CY001270，CY001358，CY001382，CY001446，CY001454，CY001577，CY001593，

CY001601，CY001657，CY001689，CY001697，CY001705，CY001745，CY001753，CY001761，CY001769，

CY001777，CY001793，CY001825，CY001841，CY001849，CY001857，CY001865，CY001889，CY001905，

CY001913，CY001921，CY001929，CY001937，CY001961，CY001969，CY001993，CY002113，CY002137，

CY002145，CY002369，CY002553，CY002561，CY002577，CY003593，CY003794，CY003217，CY006069，

CY003601，CY003633，CY000746，CY001414，CY001833，CY002161，CY002313，CY003225，CY003233，

CY003441，CY003802，CY001350，CY006164，CY007636，CY009109，CY001609，AF386769，AJ458305，

CY001801，CY001817，CY002121，CY001478，CY001486，CY001494，CY001569，CY001585，CY001673，

CY001785，CY002377，CY002545，CY002385，CY006252，CY003561，CY006540，CY006788，CY006532，

CY006284，CY006460，CY006572，CY006580，CY008181，CY006604，CY006772，CY006484，CY006492

CY006500，CY006516，CY006548，CY006588，CY006596，CY006636，CY006796，CY006804，CY006556，

CY006564，CY006620，CY008533，CY008925，CY008941，CY008949，CY008957，CY008965，CY008973，

CY008981，CY006476，CY001505，AJ458307，AJ458308，AF255369，AF255370，CY006228，CY006244，CY006276，

CY006452，CY006236，CY006260，CY006468，CY006444，CY006508，CY006524，CY006612，CY006628，

CY008933，CY006268，AF038274，AJ458306，AF038271，AF038272，AF038273，AJ458339，CY002273，U65565，

U65568，U65569，U65570，U65572，U65573，U65574，U65575，U65576，U65577，U65578，CY006340，CY003753，

CY006332，U65563，U65564，U65566，U65567，U65571，CY006348，CY009013，U65561，U65562，CY003713，

CY003065，CY008741，L18995，L18999，AF401293，M63516，CY003513，CY003353，CY008725，CY008733，

CY003545，CY002089，CY002753，CY008717，CY003521，CY003537，CY003505，CY008453，CY009069，

CY008669，CY008709，CY006324，CY003745，CY008173，CY006316，CY006852，CY003721，CY003737，

CY009053，CY006053，U08863，CY006756，AF348912，AF348913，CY007628，CY003489，CY006100，CY006892，

CY007620，CY008469，CY006204，CY008661，K01140，CY006692，CY006700，CY006708，CY007612，CY006732，

CY006740，CY006844，CY006764，CY006724，CY006836，CY006884，CY009061，CY008693，CY008701，

CY006045，CY003729，CY006908， CY0003497，CY006828，CY006716，CY006820，CY009005，CY006812，

CY003529，X08090，X08092，CY002097，CY003553，J02167，CY002745，CY006308，CY008461，CY008685，

CY008677，AY210266，AY210267，AY210268，AY210269，AY210270，CY002497，CY006220，AY210262，

AY210263，AY210264，AY210265，CY006684，AY210258，AY210259，AY210260，AY210261，CY006300，

AY210253，AY210254，AY210255，AY210256，AY210257，CY008157，M63515，AF348188，AF348191，AF348192，

AF348193，AF348195，AF348196，AF348197，CY006212，AF348189，AF348190，AF348194，AY210239，AY210240，

AY210241，AY210242，AY210243，AY210244，AY210245，AY210246，AY210247，AY210248，AY210249，

AY210250，AY210251，AY210252，DQ360841，DQ094271，DQ094272，DQ094273，DQ094274，DQ094275，

DQ372592，DQ094266，DQ094267，AY818144，AY651387，AY651388，AY651389，AY651390，AB212057，

AY575894，AY575893，AF255374，AJ278648，AF036358，AF255365，AF255366，AF255367，AF255368，AF255371，

AF255372，AF255373，AF046090，AF084282，AF084284，AF115286，DQ226095，AF255363，AF255364，AJ278647，

AJ278646

表1-8用于该分析的NS序列(片段8)的Genebank登记号

CY007471，CY002540，CY002628，CY002684，CY002692，CY002708，CY002812，CY002988，CY003300，

CY003380，CY003388，CY003692，CY003708，CY006199，CY006431，CY006671，CY006919，CY008528，

CY009000，CY002532，CY003308，CY006679，DQ249269，CY001956，CY002396，CY002404，CY002572，

CY002620，CY002676，CY002700，CY002804，CY003004，CY003012，CY003020，CY003028，CY003292，

CY003316，CY003324，CY003332，CY003396，CY003404，CY003468，CY003476，CY003484，CY003837，

CY006175，CY006359，CY006367，CY006423，CY006783，CY006879，CY008152，CY009240，CY002644，

CY002652，CY009176，CY009184，CY009192，CY009200，CY009208，CY009224，CY009232，AF258521，

AF342817，AF258520，AF055423，AF055424，AF055425，AF398877，U53170，U53171，AF055422，CY009320，

M57643，M80974，M12593，M12594，AJ298950，X15282，M12595，CY009288，CY009296，K00578，CY008992，

M12592，CY009368，CY009344，X52146，CY009336，K00576，K00577，U02087，M12596，U13682，AF389122，

L25720，M12597，U13683，Z21498，AF333238，CY002156，CY002356，CY002364，CY002636，CY002660，

CY002668，CY002996，CY003676，CY003700，CY003765，CY006111，CY006191，CY006391，CY006399，

CY006407，CY006415，CY006751，CY006871，AB126628，AB126636，AJ519455，CY001684，CY003372，

CY003773，AY210191，AY210192，M12590，AY210182，AY210183，AY210184，AY210185，AY210186，AY210187，

AY210188，AY210189，AY210190，AY210178，AY210179，AY210180，AY210181，AY210174，AY210175，

AY210176，AY210177，AY210171，AY210172，AY210173，AY210168，AY210169，AY210170，AY210164，

AY210165，AY210166，AY210167，AY210162，AY210163，AY210160，AY210161，M23968，AY210158，AY210159，

AY210156，AY210157，AY210151，AY210152，AY210153，AY210154，AY210155，M81572，M81578，M81584，

CY002004，CY002012，CY002020，CY002036，CY002060，CY002076，CY002188，CY002204，CY002244，

CY002268，CY002452，CY002460，CY002468，CY002484，CY002492，CY002724，CY002740，CY002780，

CY003052，CY003060，CY003348，CY003644，CY003652，CY006080，CY006088，CY006127，CY006135，

CY006143，CY006151，CY006159，CY006295，CY007799，CY007807，CY007815，CY008344，CY008352，

CY008360，CY008368，CY008376，CY008384，CY008392，CY008400，CY008408，CY008416，CY008424，

CY008432，CY008440，CY008448，CY008560，CY008568，CY008576，CY008584，CY008592，CY008600，

CY008608，CY008616，CY008624，CY008632，CY008640，CY008648，CY008656，CY009032，CY009040，

CY009048，CY000037，CY000261，CY000373，CY000565，CY000765，CY000893，CY001033，CY001233，

CY002028，CY002044，CY002052，CY002068，CY002084，CY002180，CY002196，CY002212，CY002220，

CY002228，CY002236，CY002252，CY002260，CY002284，CY002292，CY002412，CY002420，CY002428，

CY002436，CY002444，CY002476，CY002508，CY002588，CY002596，CY002604，CY002612，CY002716，

CY002732，CY002764，CY002772，CY002788，CY002796，CY002910，CY002918，CY002926，CY002934，

CY002942，CY002950，CY002958，CY002966，CY002973，CY002980，CY003036，CY003044，CY003076，

CY003340，CY003412，CY003420，CY003660，CY003668，CY006096，CY006119，CY006183，CY006375，

CY006383，CY006439，CY007279，CY007287，CY007295，CY007303，CY007311，CY007319，CY007327，

CY007335，CY007343，CY007351，CY007359，CY007367，CY007375，CY007383，CY007391，CY007399，

CY007407，CY007415，CY007423，CY007431，CY007439，CY007447，CY007455，CY007463，CY007479，

CY007487，CY007495，CY007503，CY007511，CY007519，CY007527，CY007535，CY007543，CY007551，

CY007559，CY007567，CY007575，CY007583，CY007647，CY008168，CY008192，CY008208，CY008216，

CY008224，CY008232，CY008240，CY008248，CY008256，CY008520，CY008912，CY009256，CY009264，

CY009272，CY000005，CY000013，CY000021，CY000029，CY000045，CY000053，CY000061，CY000069，

CY000077，CY000085，CY000093，CY000101，CY000109，CY000125，CY000133，CY000141，CY000149，

CY000157，CY000165，CY000173，CY000181，CY000197，CY000253，CY000269，CY000349，CY000357，

CY000365，CY000381，CY000477，CY000509，CY000516，CY000525，CY000757，CY000773，CY000781，

CY000789，CY000869，CY000877，CY000885，CY000905，CY000913，CY000921，CY000953，CY000961，

CY000969，CY000977，CY001017，CY001025，CY001041，CY001049，CY001057，CY001068，CY001092，

CY001100，CY001116，CY001164，CY001193，CY001209，CY001217，CY001225，CY001257，CY001289，

CY001297，CY001345，CY001377，CY001409，CY001425，CY001465，CY001473，CY001516，CY001540，

CY001548，CY001556，CY001564，CY001628，CY001636，CY001644，CY001652，CY001716，CY002108，

CY002348，CY002524，CY003684，CY006863，CY006927，CY006935，CY006943，CY006951，CY006959，

CY006967，CY006975，CY006983，CY006991，CY006999，CY007007，CY007015，CY007023，CY007031，

CY007039，CY007047，CY007055，CY007063，CY007071，CY007079，CY007087，CY007095，CY007103，

CY007111，CY007119，CY007127，CY007135，CY007143，CY007151，CY007159，CY007167，CY007175，

CY007183，CY007191，CY007199，CY007207，CY007215，CY007223，CY007231，CY007239，CY007247，

CY007255，CY007263，CY007271，CY008200，CY008544，CY008552，CY008872，CY008880，CY008888，

CY008896，CY008904，CY008920，CY009024，CY009248，CY000117，CY000213，CY000221，CY000229，

CY000237，CY000245，CY000285，CY000293，CY000301，CY000317，CY000333，CY000341，CY000397，

CY000405，CY000413，CY000421，CY000429，CY000437，CY000445，CY000493，CY000501，CY000533，

CY000541，CY000549，CY000557，CY000589，CY000629，CY000797，CY000929，CY000937，CY000945，

CY001076，CY001084，CY001108，CY001132，CY001148，CY001156，CY001188，CY001201，CY001241，

CY001265，CY001305，CY001313，CY001321，CY001329，CY001337，CY001433，CY001441，CY001732，

CY001740，CY001948，CY002132，CY003100，CY003108，CY003116，CY003125，CY003131，CY003140，

CY003148，CY003156，CY003164，CY003172，CY003180，CY003188，CY003196，CY003204，CY003212，

CY003428，CY003781，CY007591，CY007599，CY007607，CY007655，CY007663，CY007671，CY007679，

CY007687，CY007695，CY007703，CY007711，CY007719，CY007727，CY007735，CY007743，CY007751，

CY007759，CY007767，CY007775，CY007783，CY007791，CY008264，CY008272，CY008280，CY008288，

CY008296，CY008304，CY008312，CY008320，CY008328，CY008336，DQ249270，CY000189，CY000205，

CY000277，CY000309，CY000325，CY000389，CY000485，CY000573，CY000580，CY001172，CY001724，

CY002332，CY002820，CY003084，CY003092，CY000453，CY000469，CY000613，CY000661，CY000669，

CY000693，CY000701，CY000709，CY000717，CY000741，CY000813，CY000821，CY000837，CY000845，

CY000853，CY000985，CY001001，CY001140，CY001249，CY001281，CY001369，CY001401，CY001524，

CY003244，CY003252，CY003260，CY003268，CY003276，CY003284，CY003452，CY003460，CY003813，

CY003821，CY003829，CY006663，CY008480，CY008488，CY008496，CY008504，CY008512，CY008752，

CY008760，CY008768，CY008776，CY008784，CY008792，CY008800，CY008808，CY008816，CY008824，

CY008832，CY008840，CY008848，CY008856，CY008864，CY009080，CY009088，CY009104，CY009120，

CY009128，CY009136，CY009144，CY009152，CY009160，CY009168，AJ293941，CY000461，CY000597，

CY000605，CY000621，CY000637，CY000645，CY000653，CY000677，CY000685，CY000725，CY000733，

CY000749，CY000805，CY000829，CY000861，CY000993，CY001009，CY001124，CY001180，CY001273，

CY001353，CY001361，CY001385，CY001417，CY001449，CY001457，CY001532，CY001580，CY001596，

CY001604，CY001612，CY001620，CY001660，CY001668，CY001692，CY001700，CY001708，CY001748，

CY001756，CY001764，CY001772，CY001780，CY001796，CY001812，CY001828，CY001836，CY001844，

CY001852，CY001860，CY001868，CY001876，CY001884，CY001892，CY001900，CY001908，CY001916，

CY001924，CY001932，CY001940，CY001964，CY001972，CY001980，CY001988，CY001996，CY002116，

CY002140，CY002148，CY002164，CY002172，CY002300，CY002308，CY002316，CY002340，CY002372，

CY002516，CY002556，CY002564，CY002580，CY003220，CY003228，CY003236，CY003436，CY003444，

CY003572，CY003580，CY003588，CY003596，CY003604，CY003612，CY003620，CY003628，CY003636，

CY003789，CY003797，CY003805，CY006064，CY006072，CY006167，CY006903，CY007639，CY009112，

CY001481，CY001489，CY001497，CY001508，CY001572，CY001588，CY001676，CY001788，CY001804，

CY001820，CY002124，CY002380，CY002388，CY002548，CY003564，CY006255，CY006287，CY006463，

CY006479，CY006487，CY006495，CY006503，CY006519，CY006535，CY006543，CY006551，CY006559，

CY006567，CY006575，CY006583，CY006591，CY006599，CY006607，CY006623，CY006639，CY006775，

CY006791，CY006799，CY006807，CY008184，CY008536，CY008928，CY008944，CY008952，CY008960，

CY008968，CY008976，CY008984，AF038279，AF256182，AF256183，CY006231，CY006239，CY006247，

CY006263，CY006271，CY006279，CY006447，CY006455，CY006471，CY006511，CY006527，CY006615，

CY006631，CY008936，AF038276，AF038277，AF038278，AF038275，CY002276，U65671，U65672，U65673，

U65674，CY003756，CY006335，CY006343，U65670，CY006351，CY009016，D30675，D30676，CY003716，D30667，

D30674，D30673，CY003068，CY008744，D30670，D30672，CY003356，CY003516，CY008728，CY008736，M57642，

CY003548，D30671，M57641，M80975，CY002092，CY002756，CY008720，M57640，CY003508，CY03524，

CY003540，CY008456，CY008672，CY008712，CY009072，M17699，CY003748，CY006327，CY008176，CY003724，

CY003740，CY006319，CY006855，CY009056，CY006056，CY006759，U08862，CY007631，CY003492，CY006103，

CY006207，CY006895，CY007623，CY008472，CY008664，CY006695，CY006703，CY006711，CY007615，

CY006735，CY006743，CY006767，CY006847，K01332，CY006727，CY006839，CY006887，CY008696，CY008704，

CY009064，CY003732，CY006048，CY003500，CY006719，CY006823，CY006831，CY006911，CY003532，

CY006815，CY009008，AY210312，AY210313，AY210314，AY210315，AY210316，CY002100，CY002748，

CY003556，CY006311，CY008464，CY008680，CY008688，V01102，AY210307，AY210309，AY210310，AY210311，

CY002500，CY006223，CY006687，AY210304，AY210305，AY210306，AY210308，AY210299，AY210300，

AY210301，AY210302，AY210303，CY006303，AF348198，AF348199，AF348200，AF348201，AF348202，AF348203，

AF348204，AF348205，AF348206，AY210285，AY210286，AY210287，AY210288，AY210289，AY210290，

AY210291，AY210292，AY210293，AY210294，AY210295，AY210296，AY210297，AY210298，CY006215，

CY008160，DQ360842，DQ372595，AY526747，AY651552，AY651553，AY651554，AY651555，AY818147，

AB212058，AB212059，AY576368，AY576369，AF256188，AF036360，AF046091，AF084285，AF084286，AF084287，AF115288，AF6178，AF256179，AF256180，AF256181，AF256184，AF256185，AF256186，AF256187，AJ404736，DQ226117，AF256177，AJ278649，AJ404735，AY043027

从所研究的每个甲型流感病毒序列选取所有19-mer序列片段，然后列表确定每个序列片段是否作为准确匹配存在于每个甲型流感病毒序列中，从而鉴别高度保守的19-mer序列片段。因此，第一病毒序列含有从位置1伸展至19的19-mer序列片段，另一个从位置2至20，另一个从位置3至21，等等。以同样方式选取第二、第三、和第四病毒序列，直到表(表1)所列的最后一个病毒序列。

随后把序列片段加至序列片段的增加的表中，保持含有各19-mer片段的甲型流感病毒序列的数目的计数。最终，片段频率以含有各特异性19-mer片段的病毒序列的百分比来表达。表2列出了最保守的19-mer序列片段(最低70％)及其发生频率。

表2-1在表1-1所列甲型流感片段1(PB2)序列中以至少70％存在的保守19-mer序列

Seq

ID          序列              百分比    51    AUGAAACGAAAACGGGACU    95.9％

                                        52    GAAAUGGAUGAUGGCAAUG    95.8％

1    GCCAGACAGCGACCAAAAG      99.5％    53    UGGAUGAUGGCAAUGAAAU    95.8％

2    AGCCAGACAGCGACCAAAA      99.5％    54    UGAAAUGGAUGAUGGCAAU    95.8％

3    ACAGCCAGACAGCGACCAA      99.3％    55    GGAUGAUGGCAAUGAAAUA    95.8％

4    GACAGCCAGACAGCGACCA      99.3％    56    UGAAACGAAAACGGGACUC    95.8％

5    CAGACAGCGACCAAAAGAA      99.3％    57    AAAUGGAUGAUGGCAAUGA    95.8％

6    CAGCCAGACAGCGACCAAA      99.3％    58    AUGGAUUGAUGCAAUGAAA    95.7％

7    AGACAGCGACCAAAAGAAU      99.1％    59    AAUGGAUGAUGGCAAUGAA    95.7％

8    CCAGACAGCGACCAAAAGA      99.1％    60    AUGAAAUGGAUGAUGGCAA    95.7％

9    ACAGCGACCAAAAGAAUUC      99.1％    61    GAAACGAAAACGGGACUCU    95.5％

10   UACUUACUGACAGCCAGAC      99.1％    62    AAACGAAAACGGGACUCUA    95.5％

11   CAGCGACCAAAAGAAUUCG      99.1％    63    AACGAAAACGGGACUCUAG    95.4％

12   ACUUACUGACAGCCAGACA      99.1％    64    GAAAACGGGACUCUAGCAU    95.4％

13   CAUACUUACUGACAGCCAG      99.1％    65    ACGAAAACGGGACUCUAGC    95.4％

14   CUUACUGACAGCCAGACAG      99.1％    66    CGAAAACGGGACUCUAGCA    95.4％

15   GACAGCGACCAAAAGAAUU      99.1％    67    AAAACGGGACUCUAGCAUA    95.3％

16   AUACUUACUGACAGCCAGA      99.1％    68    GAAAGGUUAAAACAUGGAA    94.9％

17   ACUGACAGCCAGACAGCGA      99.0％    69    AAAGGUUAAAACAUGGAAC    94.9％

18   GCAUACUUACUGACAGCCA      99.0％    70    AAGGUUAAAACAUGGAACC    94.8％

19   AGCAUACUUACUGACAGCC      99.0％    71    GGUUAAAACAUGGAACCUU    94.8％

20   UGACAGCCAGACAGCGACC      99.0％    72    AGGUUAAAACAUGGAACCU    94.8％

21   UACUGACAGCCAGACAGCG      99.0％    73    CUCGCACUCGCGAGAUACU    94.5％

22   UUACUGACAGCCAGACAGC      99.0％    74    UCUCGCACUCGCGAGAUAC    94.5％

23   CUGACAGCCAGACAGCGAC      99.0％    75    UAAAAGCAGUUAGAGGUGA    94.3％

24   ACUCUAGCAUACUUACUGA      98.9％    76    UCGGAUGGCCAUCAAUUAA    94.2％

25   UAGCAUACUUACUGACAGC      98.7％    77    AGGAUGAAAUGGAUGAUGG    94.0％

26   CUCUAGCAUACUUACUGAC      98.6％    78    GGAUGAAAUGGAUGAUGGC    94.0％

27   CUAGCAUACUUACUGACAG      98.6％    79    UUAGGAUGAAAUGGAUGAU    93.9％

28   UCUAGCAUACUUACUGACA      98.6％    80    AUGGUUGCAUACAUGUUAG    93.9％

29   CAAAAGAAUUCGGAUGGCC      98.6％    81    UAGGAUGAAAUGGAUGAUG    93.9％

30   AAAAGAAUUCGGAUGGCCA      98.6％    82    UGGUUGCAUACAUGUUAGA    93.9％

31   GACCAAAAGAAUUCGGAUG      98.5％    83    CUUAGGAUGAAAUGGAUGA    93.9％

32   CGACCAAAAGAAUUCGGAU      98.5％    84    UUGCAUACAUGUUAGAGAG    93.9％

33   AAAGAAUUCGGAUGGCCAU      98.5％    85    ACUUAGGAUGAAAUGGAUG    93.9％

34   AGCGACCAAAAGAAUUCGG      98.5％    86    GUUGCAUACAUGUUAGAGA    93.8％

35   GCGACCAAAAGAAUUCGGA      98.5％    87    UAAAACAUGGAACCUUUGG    93.8％

36   CCAAAAGAAUUCGGAUGGC      98.5％    88    UUAAAACAUGGAACCUUUG    93.8％

37   ACCAAAAGAAUUCGGAUGG      98.5％    89    GGUUGCAUACAUGUUAGAG    93.8％

38   GAAUUCGGAUGGCCAUCAA      98.4％    90    UGAUGGUUGCAUACAUGUU    93.7％

39   UUCGGAUGGCCAUCAAUUA      98.3％    91    AUGAGAAUACUUGUAAGGG    93.7％

40   AUUCGGAUGGCCAUCAAUU      98.3％    92    UGAGAAUACUUGUAAGGGG    93.7％

41   GACUCUAGCAUACUUACUG      98.3％    93    CACUUAGGAUGAAAUGGAU    93.7％

42   AGAAUUCGGAUGGCCAUCA      98.3％    94    GUUAAAACAUGGAACCUUU    93.7％

43   AAGAAUUCGGAUGGCCAUC      98.3％    95    UUGAUGGUUGCAUACAUGU    93.5％

44   AAUUCGGAUGGCCAUCAAU      98.3％    96    GAUGGUUGCAUACAUGUUA    93.4％

45   GGGACUCUAGCAUACUUAC      98.1％    97    UCACUUAGGAUGAAAUGGA    93.3％

46   ACGGGACUCUAGCAUACUU      98.0％    98    AACAUGGAACCUUUGGCCC    93.1％

47   AAACGGGACUCUAGCAUAC      98.0％    99    AAACAUGGGAACCUUGGCC    93.1％

48   CGGGACUCUAGCAUACUUA      98.0％    100   CAAGCUGUGGAUAUAUGCA    92.9％

49   AACGGGACUCUAGCAUACU      98.0％    101   AAGCUGUGGAUAUAUGCAA    92.9％

50   GGACUCUAGCAUACUUUACU     97.9％    102   AAAACAUGGAACCUUGGGC    92.8％

103   GUAUGAAAACCGAAAAGGG    92.6％    157   ACUCCAGGUGGAGAAGUGA    87.1％

104   UAAUGAAACGAAAACGGGA    92.6％    158   GAUUGCAUGAUAAAAGCAG    87.0％

105   AAUGAAACGAAAACGGGAC    92.6％    159   CCAGGUGGAGAAGUGAGGA    87.0％

106   GAUGAAAUGGAUGAUGGCA    92.3％    160   CAUACAAUGUUAGAGAGGA    87.0％

107   AACAAGCUGUGGAUAUAUG    91.3％    161   GCAUGAUAAAAGCAGUUAG    87.0％

108   GAACAAGCUGUGGAUAUAU    91.3％    162   AUUGCAUGAUAAAAGCAGU    87.0％

109   ACAAGCUGUGGAUAUAUGC    91.2％    163   GCAUACAUGUUAGAGAGAG    87.0％

110   UGUACACUCCAGGUGGAGA    90.0％    164   CUCCAGGUGGAGAAGUGAG    87.0％

111   AUGUACACUCCAGGUGGAG    90.0％    165   CAUGAUAAAAGCAGUUAGA    87.0％

112   AGAACAAGCUGUGGAUAUA    89.8％    166   GUGGAGAAGUGAGGAAUGA    86.9％

113   GAAGAACCAGCUGUGGAUA    89.8％    167   UGCAUGAUAAAAGCAGUUA    86.9％

114   AAGAACAAGCUGUGGAUAU    89.8％    168   CAGGUGGAGAAGUGAGGAA    86.9％

115   UGAUAAAAGCAGUUAGAGG    89.7％    169   GGUGGAGAAGUGAGGAAUG    86.9％

116   AUGAUAAAAGCAGUUAGAG    89.6％    170   UUGCAUGAUAAAAGCAGUU    86.8％

117   ACAUGGUGGAAUAGAAAUG    89.3％    171   AGGUGGAGAAGUGAGGAAU    86.8％

118   CAUGGUGGAAUAGAAAUGG    89.3％    172   UGCAUACAUGUUAGAGAGA    86.7％

119   CGGAUGGCCAUCAAUUAAU    89.1％    173   AAAGAAUAAAAGAACUACG    86.6％

120   GAUAAAAGCAGUUAGAGGU    88.9％    174   GAGAUGUGCCACAGCACAC    86.6％

121   AUAAAAGCAGUUAGAGGUG    88.9％    175   UAAGAGUCAGCAAAAUGGG    86.6％

122   AUAUGGCCAUAAUUAAGAA    88.8％    176   CCAUAUGGCCAUAAAUAAG    86.5％

123   CAUAUGGCCAUAAUUAAGA    88.8％    177   GAUUUCUCCCAGUUGCUGG    86.5％

124   UGGAAAGAAUAAAAGAACU    88.5％    178   AGAUUUCUCCCAGUUGCUG    86.5％

125   UGGUGGAAUAGAAAUGGAC    88.5％    179   AGGAGGUCAGUGAAACACA    86.4％

126   AUGGAAAGAAUAAAAGAAC    88.5％    180   GAGGAGGUCAGUGAAACAC    86.4％

127   GGUGGAAUAGAAAUGGACC    88.4％    181   GAAAGAAUAAAAGAACUAC    86.4％

128   GGAAAGAAUAAAAGAACUA    88.4％    182   AUACAUGUUAGAGAGAGAA    86.2％

129   AUGGUGGAAUAGAAAUGGA    8804％    183   AGGGAUGAGAAUACUUGUA    86.1％

130   AUGGCCAUAAUUAAGAAGU    88.1％    184   UAUGCAAGGCUGCAAUGGG    86.1％

131   UGGCCAUAAUUAAGAAGUA    88.1％    185   GGAUGAGAGUACUUGUAAG    86.1％

132   AGUCUCGCACUCGCGAGAU    88.1％    186   GCACAGAGAUGUCAAUGAG    86.1％

133   GUCUCGCACUCGCGAGAUA    88.1％    187   GAAAAGAACCCGUCACUUA    86.1％

134   UAUUCAACUACAACAAGAC    88.1％    188   AGCACAGAGAUGUCAAUGA    86.1％

135   CAGUCUCGCACUCGCGAGA    88.1％    189   AUAUGCAAGGCUGCAAUGG    86.1％

136   UAUGGCCAUAAUUAAGAAG    88.0％    190   GGGAUGAGAAUACUUGUAA    86.1％

137   GACCAUAUGGCCAUAAUUA    87.8％    191   AAAAGAACCCGUCACUUAG    86.1％

138   UGGACCAUAUGGCCAUAAU    87.7％    192   UCAGGGAUGAGAAUACUUG    86.1％

139   GUAUUCAACUACAACAAGA    87.7％    193   CAGGGAUGAGAAUACUUGU    86.1％

140   GUGGACCAUAUGGCCAUAA    87.7％    194   CCAAGCACAGAGAUGUCAA    86.0％

141   CAUGUUAGAGAGAGAACUU    87.6％    195   CAGGAAAAGAACCCGUCAC    86.0％

142   UACAUGUUAGAGAGAGAAC    87.6％    196   CCACAGUGGACCAUAUGGC    86.0％

143   ACAUGUUAGAGAGAGAACU    87.6％    197   AGGAAAAGAACCCGUCACU    86.％

144   ACCAUAUGGCCAUAAUUAA    87.6％    198   ACCACAGUGGGACCAUAUG    86.0％

145   UGUUAGAGAGAGAACUUGU    87.6％    199   CAGUGGACCAUAUGGCCAU    86.0％

146   AUGUUAGAGAGAGAACUUG    87.6％    200   GAAUACUUGUAAGGGGCAA    86.0％

147   ACACUCCAGGUGGAGAAGU    87.4％    201   AGAUGUGCCACAGCACACA    86.0％

148   AUGUCGCAGUCUCGCACUC    87.4％    202   GGAAAAGAACCCGUCACUU    86.0％

149   GUACACUCCAGGUGGAGAA    87.4％    203   AAGCACAGAGAUGUCAAUG    86.0％

150   UACACUCCAGGUGGAGAAG    87.4％    204   AGAAUACUUGUAAGGGGCA    86.0％

151   UGUCGCAGUCUCGCACUCG    87.4％    205   GGACCAUAUGGCCAUAAUU    86.0％

152   UCGCAGUCUCGCACUCGCG    87.3％    206   ACAGUGGACCAUAUGGCCA    86.0％

153   GUCGCAGUCUCGCACUCGC    87.3％    207   AGUGGACCAUAUGGCCAUA    86.0％

154   GCAGUCUCGCACUCGCGAG    87.2％    208   CAAGCACAGAGAUGUCAAU    86.0％

155   CGCAGUCUCGCACUCGCGA    87.2％    209   GAGAAUACUUGUAAGGGGC    86.0％

156   CACUCCAGGUGGAGAAGUG    87.2％    210   GACAGGAAAAGAACCCGUC    85.9％

211   AUCGAGUGAUGGCAUCACC    85.9％    265   AGGUCAGUGAAACACAGGG    85.3％

212   GCUGUGGAUAUAUGCAAGG    85.9％    266   GGGGAUCAGGGAUGAGAAU    85.3％

213   GGAUAUAUGCAAGGCUGCA    85.9％    267   GAGGUCAGUGAAACACAGG    85.3％

214   UGGAUAAUAUGCAAGCUGC    85.9％    268   UUGUAAGGGGCAAUUCUCC    85.3％

215   AGACAGGAAAAGAACCCGU    85.9％    269   GGGAGACAGGAAAAGAACC    85.3％

216   ACAAAAACCACAGUGGACC    85.9％    270   GGAGACAGGAAAAGAACCC    85.3％

217   UUUGCAGCCGCUCCACCAA    85.9％    271   GGGAUCAGGGAUGAGAAUA    85.3％

218   CUGUGGAUAUAUGCAAGGC    85.9％    272   CUUGUAAGGGGCAAUUCUC    85.3％

219   GUGGAUAUAUGCAAGGCUG    85.9％    273   ACUUGUAAGGGGCAAUUCU    85.3％

220   ACAGGAAAAGAACCCGUCA    85.9％    274   AGAAUCAGCUCAUCCUUCA    85.1％

221   CGAAGAUGUCAAUGAGAGG    85.9％    275   GGUAAUGAAACGAAAACGG    85.1％

222   GAUCGAGUGAUGGUAUCAC    85.9％    276   UGAGGGGAUCAGGGAUGAG    85.1％

223   UAUAUGCAAGGCUGCAAUG    85.9％    277   GUGAGGGGAUCAGGGAUGA    85.1％

224   AUAUAUGCAAGGCUGCAAU    85.9％    278   AUGUGAGGGGAUCAGGGAU    85.1％

225   UCCAGGUGGAGAAGUGAGG    85.9％    279   GAGGGGAUCAGGGAUGAGA    85.1％

226   CAAAAACCACAGUGGACCA    85.9％    280   ACCACCCAGAUAAUAAAGC    85.1％

227   UUGCAGCCGCUCCACCAAA    85.9％    281   AAUGUGAGGGGAUCAGGGA    85.1％

228   UACUCAGAAAAGCAACCAG    85.8％    282   CCACCCAGAUAAUAAAGCU    85.1％

229   AUAAUUAAGAAGUACACAU    85.8％    283   UGUGAGGGGAUCAGGGAUG    85.1％

230   AAAAACCACAGUGGACCAU    85.8％    284   GCUAUACUCAGAAAAGCAA    85.0％

231   AUACUCAGAAAAGCAACCA    85.8％    285   CUAUACUCAGAAAAGCAAC    85.0％

232   GAUAUAUGCAAGGCUGCAA    85.8％    286   GAAUCAGCUCAUCCUUCAG    85.0％

233   AAAACCACAGUGGACCAUA    85.8％    287   CCUGAGGAGGUCAGUGAAA    84.9％

234   AAGAAUAAAAGAACUACGG    85.8％    288   CUGAGGAGGUCAGUGAAAC    84.9％

235   UACAACAAAAUGGAAUUUG    85.8％    289   UAUACUCAGAAAAGCAACC    84.9％

236   ACAACAAAAUGGAAUUUGA    85.8％    290   CAACAGCUAUACUCAGAAA    84.8％

237   AAACCACAGUGGACCAUAU    85.8％    291   AUGGAACCUUUGGCCCUGU    84.8％

238   CACAGUGGACCAUAUGGCC    85.8％    292   GCAACAGCUAUACUCAGAA    8A.8％

239   CACAGAGAUGUCAAUGAGA    85.8％    293   AUAAGAGUCAGCAAAAUGG    84.8％

240   UAAUUAAGAAGUACACAUC    85.8％    294   UGAGGAGGUCAGUGAAACA    84.6％

241   ACAGAGAUGUCAAUGAGAG    85.8％    295   UUUUAAGGCAUUUUCAGAA    84.6％

242   AACCACAGUGGACCAUAUG    85.8％    296   CUCUAUUCCAACAAAUGAG    84.6％

243   AUCAGGGAUGAGAAUACUU    85.7％    297   ACUCUAUUCCAACAAAUGA    84.6％

244   AGAAUAAAAGAACUACGGA    85.7％    298   GAACCCGUCACUUAGGAUG    84.6％

245   AUACUUGUAAGGGGCAAUU    85.7％    299   AAGAACCCGUCACUUAGGA    84.6％

246   GAUCAGGGAUGAGAAUACU    85.7％    300   AGAACCCGUCACUUAGGAU    84.6％

247   AGCUGUGGAUAUAUGCAAG    85.7％    301   AACAGCUAUACUCAGAAAA    84.6％

248   CCAUAAUUAAGAAGUACAC    85.7％    302   AGAUAAUAAAGCUUCUCCC    84.5％

249   UGUGGAUAUAUGCAAGGCU    85.7％    303   CCCAGAUAAUAAAGCUUCU    84.5％

250   UACUUGUAAGGGGCAAUUC    85.7％    304   CAGAUAAUAAAGCUUCUCC    84.5％

251   AAUACUUGUAAGGGGCAAU    85.7％    305   CUUUUAAGGCAUUUUCAGA    84.5％

252   GGAUCAGGGAUGAGAAUAC    85.7％    306   GUAAUUAUGGAAGUUGUUU    84.4％

253   CAUAAUUAAGAAGUACACA    85.7％    307   ACCCAGAUAAUAAAGCUUC    84.4％

254   ACCCGUCACUUAGGAUGAA    85.6％    308   AUGUAAUUAUGGAAGUUGU    84.4％

255   CCGUCACUUAGGAUGAAAU    85.6％    309   CCUGGUCAUGCAGACCUCA    84.4％

256   GUCAUCUAGGAUGAAAUGG    85.6％    310   GAUGUAAUUAUGGAAGUUG    84.4％

257   GCCAUAAUUAACAAGUACA    85.6％    311   UCCUGAGGAGGUCAGUGAA    84.4％

258   CGUCACUUAGGAUGAAAUG    85.6％    312   CUCCUGAGGAGGUCAGUGA    84.4％

259   CCCGUCACUUAGGAUGAAA    85.6％    313   UAAUUAUGGAAGUUGUUUU    84.4％

260   GGCCAUAAUUAAGAAGUAC    85.6％    314   CACCCAGAUAAUAAAGCUU    84.4％

261   AACCCGUCACUUAGGAUGA    85.6％    315   UGGAGAUGUGCCACAGCAC    84.4％

262   UGGUAAUGAAACGAAAACG    85.4％    316   UCUCCUGAGGAGGUCAGUG    84.4％

263   UUGGUAAUGAAACGGAAAC    85.4％    317   ACAGCUAUACUCAGAAAAG    84.4％

264   AGGGGAUCAGGGAUGAGAA    85.3％    318   CCACUAGCAUCUUUAUUGG    84.4％

319   CACUAGCAUCUUUAUUGGA    84.4％    373   CAGCCGCUCCACCAAAGCA    83.5％

320   CUGGUCAUGCAGACCUCAG    84.3％    374   GCAGCCGCUCCACCAAAGC    83.5％

321   CAUGGAACCUUUGGCCCUG    84.3％    375   GGCAUUUUCAGAAAGAUGC    83.4％

322   UGUAAUUAUGGAAGUUGUU    84.3％    376   AGGCAUUUUCAGAAAGAUG    83.4％

323   CAGCUAUACUCAGAAAAGC    84.2％    377   UAAGGCAUUUUCAGAAAGA    83.4％

324   AUUCUCCUGUAUUCAACUA    84.2％    378   ACUUUAAUUGAAGACCCAG    83.4％

325   AAGAACCCGUCACUUUAGG    84.2％    379   AAGGCAUUUUCAGAAAGAU    83.4％

326   UUGGAGAUGUGCCACAGCA    84.2％    380   UUAGGGCAUUUUCAGAAAG    83.4％

327   AAUUCUCCUGUAUUCAACU    84.2％    381   GCAAUCUCCAAACAUUGAA    83.4％

328   ACAUGGAACCUUUGGCCCU    84.1％    382   GCACUUUAAUUGAAGACCC    83.3％

329   GGAGAUGUGCCACAGCACA    84.1％    383   CACUUUAAUUGAAGACCCA    83.3％

330   UCAGAUCGAGUGAUGGUAU    84.1％    384   CUUUAAUUGAAGACCCAGA    83.3％

331   UAUUGGAGAUGUGCCACAG    84.1％    385   GGCACUUUAAUUGAAGACC    83.3％

332   AGAUCGAGUGAUGGUAUCA    84.1％    386   UUUAAGGCAUUUUCAGAAA    83.2％

333   CAGAUCGAGUGAUGGUAUC    84.1％    387   UUUAAUUGAAGACCCAGAU    83.2％

334   CCAGAUAAUAAAGCUUCUC    84.1％    388   UUUGAGAGUUCGAGACCAA    83.2％

335   AUUGGAGAUGUGCCACAGC    84.1％    389   UUUUUGAGAGUUCGAGACC    83.2％

336   AGCUAUACUCAGAAAAGCA    84.0％    390   GCCGCUCCACCAAAGCAAA    83.2％

337   GGCAAUUCUCCUGUAUUCA    84.0％    391   UUUUGAGAGUUCGAGACCA    83.2％

338   CUUUAUUGGAGAUGUGCCA    84.0％    392   AGCCGCUCCACCAAAGCAA    83.2％

339   UUAUUGGAGAUGUGCCACA    84.0％    393   UUAAUUGAAGACCCAGAUG    83.2％

340   UCCAAGCACAGAGAUGUCA    84.0％    394   UGCAGCCGCUCCACCAAAG    83.2％

341   UCUUUAUUGGAGAUGUGCC    84.0％    395   CCGCUCCACCAAAGCAAAG    83.2％

342   GCAAUUCUCCUGUAUUCAA    83.9％    396   UAAUUGAAGACCCAGAUGA    83.0％

343   CUCCAAGCACAGAGAUGUC    83.9％    397   UUGAGAGUUCGAGACCAAC    83.0％

344   GCCAUGGUGUUUUCACAAG    83.9％    398   UUCACAAUGGUGGGGAAAA    83.0％

345   GAGACAGGAAAAGAACCCG    83.9％    399   UAAACCCUGGUCAUGCAGA    82.9％

346   UUUAUUGGAGAUGUGCCAC    83.9％    400   UUCAAUGGUCUCAGAAUCC    82.9％

347   CAUCUUUAUUGGAGAUGUG    83.9％    401   UCACAAUGGUGGGGAAAAG    82.9％

348   CCAUGGUGUUUUCACAAGA    83.9％    402   UCAAUGGUCUCAGAAUCCU    82.9％

349   GGAGGUCAGUGAAACACAG    83.9％    403   UCGAGUGAUGGUAUCACCU    82.9％

350   AAAAUUCAAUGGUCUCAGA    83.9％    404   AUUCAAUGGUCUCAGAAUC    82.9％

351   AAAUUCAAUGGUCUCAGAA    83.8％    405   AAUUCAAUGGUCUCAGAAU    82.9％

352   AGCAUCUUUAUUGGAGAUG    83.8％    406   UCAGUGAAACACAGGGAAC    82.8％

353   AUGACUCCAAGCACAGAGA    83.8％    407   AUAAACCCUGGUCAUGCAG    82.8％

354   CUAGCAUCUUUAUUGGAGA    83.8％    408   ACCCUGGUCAUGCAGACCU    82.8％

355   GCAUCUUUAUUGGAGAUGU    83.8％    409   AAACCCUGGUCAUGCAGAC    82.8％

356   GACAUAAACCCUGGUCAUG    83.8％    410   AACCCUGGUCAUGCAGACC    82.8％

357   UAUCUCCUGAGGAGGUCAG    83.8％    411   GUCAGUGAAACACAGGGAA    82.7％

358   CAAUUCUCCUGUAUUCAAC    83.8％    412   GAGGAUUGCAUGAUAAAAG    82.7％

359   GAUGAGAAUACUUGUAAGG    83.8％    413   GUAAGGGGCAAUUCUCCUG    82.7％

360   UAGCAUCUUUAUUGGAGAU    83.8％    414   AGGAUUGCAUGAUAAAAGC    82.7％

361   AUCUUUAUUGGAGAUGUGC    83.7％    415   UGUAAGGGGCAAUUCUCCU    82.7％

362   UGACUCCAAGCACAGAGAU    83.7％    416   CAUAAACCCUGGUCAUGCA    82.7％

363   AUCUCCUGAGGAGGUCAGU    83.7％    417   UGAGAGUUCGAGACCAACG    82.6％

364   ACAUAAACCCUGGUCAUGC    83.7％    418   CAAGAGGAUUGCAUGAUAA    82.6％

365   GAGAAUCAGCUCAUCCUUC    83.7％    419   AAGAGGAUUGCAUGAUAAA    82.6％

366   UGAGAAUCAGCUCAUCCUU    83.7％    420   UCACAAGAGGAUUGCAUGA    82.5％

367   GACUCCAAGCACAGAGAUG    83.7％    421   UAAGGGGCAAUUCUCCUGU    82.5％

368   ACUAGCAUCUUUAUUGGAG    83.7％    422   GGAUUGCAUGAUAAAAGCA    82.5％

369   ACUCCAAGCACAGAGAUGU    83.7％    423   CACAAGAGGAUUGCAUGAU    82.5％

370   AAGGAACGUGUUGGGAACA    83.6％    424   AGAGGAUUGCAUGAUAAAA    82.5％

371   CAAGGAACGUGUUGGGAAC    83.6％    425   ACAGAAGGAUUGCAUGAUA    82.5％

372   GGCAAUCUCCAAACAUUGA    83.6％    426   GUGUUUUCACAAGAGGAUU    82.4％

427   UGUUUUCACAAGAGGAUUG    82.4％    481    CAUGGUGUUUUCACAAGAG    80.8％

428   AAGAAGUGCUUACAGGCAA    82.3％    482    AAUGUUGUACAACAAAAUG    80.8％

429   UUCACAAGAGGAUUGCAUG    82.3％    483    GGUGUUUUCACAAGAGGAU    80.8％

430   UUUCACAAGAGGAUUGCAU    82.3％    484    ACAAGGAUGGUGGACAUUC    80.6％

431   GUUUUCACAAGAGGAUUGC    82.3％    485    CAAGGAUGGUGGACAUUCU    80.6％

432   GAAGAAGUGCUUACAGGCA    82.3％    486    AACUACAAAAGGACCACUA    80.6％

433   UUUUCACAAGGAGAUUGCA    82.3％    487    ACUACAACAAGACCACUAA    80.6％

434   GCCAAUACAGUGGGUUUGU    82.2％    488    GCAGAUCCACUAGCAUCUU    80.5％

435   AGGGGCAAUUCUCCUGUAU    82.1％    489    CAGAUCCACUAGCAUCUUU    80.5％

436   UUAGAGGUGACCUGAAUUU    82.1％    490    GUGAUGGUAUCACCUUUGG    80.4％

437   UGGAAUUUGAACCAUUUCA    82.1％    491    UGAUGGUAUCACCUUUGGC    80.4％

438   GGGGCAAUUCUCCUGUAUU    82.1％    492    AGAUACGGACCAGCAUUAA    80.4％

439   AAGGGGCAAUUCUCCUGUA    82.1％    493    GAGUGAUGGUAUCACCUUU    80.4％

440   AUGGAAUUUGAACCAUUUC    82.1％    494    AUCCACUAGCAUCUUUAUU    80.3％

441   GUUAGAGGUGACCUGAAUU    82.1％    495    GAUACGGACCAGCAUUAAG    80.3％

442   AAAAUGGAAUUUGAACCAU    82.0％    496    AGAUCCACUAGCAUCUUUA    80.3％

443   UGUACAACAAAAUGGAAUU    82.0％    497    GAUCCACUAGCAUCUUUAU    80.3％

444   AAAUGGAAUUUGAACCAUU    82.0％    498    CGAGUGAUGGUAUCACCUU    80.3％

445   GUACAACAAAAUGGAAUUU    82.0％    499    CAACUACAACAAGACCACU    80.3％

446   CAGUUAGAGGUGACCUGAA    81.9％    500    UUACAGGCAAUCUCCAAAC    80.2％

447   GAGGUGACCUGAAUUUCGU    81.8％    501    ACAGGCAAUCUCCAAACAU    80.2％

448   AGAGGUGACCUGAAUUUCG    81.8％    502    CUUACAGGCAAUCUCCAAA    80.2％

449   UAGAGGUGACCUGAAUUUC    81.8％    503    UACAGGCAAUCUCCAAACA    80.2％

450   AAAGCAGUUAGAGGUGACC    81.8％    504    CAGGCAAUCUCCAAACAUU    80.2％

451   AAGCAGUUAGAGGUGACCU    81.8％    505    AGUGAUGGUAUCACCUUUG    80.2％

452   AAAAGCAGUUAGAGGUGAC    81.8％    506    AGGCAAUCUCCAAACAUUG    79.9％

453   AGUUAGAGGUGACCUGAAU    81.8％    507    UAUGGAAAGAAUAAAAGAA    79.9％

454   GCAGUUAGAGGUGACCUGA    81.8％    508    AAGAUACGGACCAGCAUUA    79.9％

455   AGCAGUUAGAGGUGACCUG    81.8％    509    AUGCGAAAGUGCUUUUUCA    79.7％

456   AAUGGAAUUUGAACCAUUU    81.7％    510    UAUCAAUGGAUCAUCAGAA    79.7％

457   GGAGAAGUGAGGAAUGACG    81.7％    511    GGAUGGUGGACAUUCUUAG    79.7％

458   GGGCAAUUCUCCUGUAUUC    81.7％    512    ACCUAUCAAUGGAUCAUCA    79.6％

459   GAGAAGUGAGGAAUGACGA    81.7％    513    GCUUACAGGCAAUCUCCAA    79.6％

460   UGGAGAAGUGAGGAAUGAC    81.6％    514    AAGGAUGGUGGACAUUCUU    79.6％

461   UUGUACAACAAAAUGGAAU    81.4％    515    AGGAUGGGUGACAUUCUUA    79.6％

462   UGUUGUACAACAAAAUGGA    81.4％    516    GAAGUGCUUACAGGCAAUC    79.6％

463   AGCAUUAAGCAUCAAUGAA    81.4％    517    AUCAAUGGAUCAUCAGAAA    79.6％

464   CAGCAUUAAGCAUCAAUGA    81.4％    518    UGCUUACAGGCAAUCUCCA    79.6％

465   CCAGCAUUAAGCAUCAAUG    81.4％    519    AAGUGCUUACAGGCAAUCU    79.6％

466   AUGUUGUACAACAAAAUGG    81.3％    520    GAAGUGAGGAAUGACGAUG    79.5％

467   GGAGUAAAAKGAGUGAUGC    81.3％    521    GUGCUUACAGGCAAUCUCC    79.5％

468   AAUUGAAGACCCAGAUGAA    81.3％    522    AAGUGAGGAAUGACGAUGU    79.5％

469   UGGAGUAAAAUGAGUGAUG    81.3％    523    AGAGACUGACAAUAACUUA    79.5％

470   UUCAACUACAACAAGACCA    81.2％    524    GAGAGACUGACAAUAACUU    79.5％

471   UCAACUACAACAAGACCAC    81.2％    525    AGAAGUGCUUACAGGCAAU    79.5％

472   GUUGUACAACAAAAUGGAA    81.2％    526    GAAGAUACGGACCAGCAUU    79.5％

473   AUGGUGUUUUCACAAGAGG    81.0％    527    GAUGCGAAAGUGCUUUUUC    79.5％

474   AUGGAGUAAAAUGAGUGAU    81.0％    528    UCAGCUCAUCCUUCAGCUU    79.5％

475   CUAUGGAGUAAAAUGAGUG    81.0％    529    AUGUGCCACAGCACACAAA    79.4％

476   UGGUGUUUUCACAAGAGGA    81.0％    530    AAUACCUAUCAAUGGAUCA    79.4％

477   UAUGGAGUAAAAUGAGUGA    81.0％    531    CCUAUCAAUGGAUCAUCAG    79.4％

478   AGAAGUGAGGAAUGACGAU    80.9％    532    AUACCUAUCAAUGGAUCAU    79.4％

479   CAAUGUUGUACAACAAAAU    80.8％    533    UGUGCCACAGCACACAAAU    79.4％

480   AUUCAACUACAACAAGACC    80.8％    534    AGAAGAUACGGACCAGCAU    79.4％

535   AGUGCUUACAGGCAAUCUC    79.4％    589    GAUAGCCAUCAAUUAAUGU    78.7％

536   AUCAGCUCAUCCUUCAGCU    79.4％    590    GUGAGGAAUGACGAUGUUG    78.7％

537   AGGAGUUCACAAUGGUGGG    79.4％    591    GUCAAUACCUAUCAAUGGA    78.7％

538   GAGGAGUUCACAAUGGUGG    79.4％    592    AGUGAGGAAUGACGAUGUU    78.7％

539   AAUCAGCUCAUCCUUCAGC    79.3％    593    GGAGUUCACAAUGGUGGGG    78.6％

540   GAUGUGCCACAGCACACAA    79.3％    594    CCACAAGCACACAAAUUGGC   78.5％

541   AGCUCAUCCUUCAGCUUUG    79.2％    595    AGAACUCUAUUCCAACAAA    78.5％

542   CUGUAUUCAACUACAACAA    79.2％    596    GAUGUCAAUGAGAGGAAUA    78.5％

543   GCUCAUCCUUCAGCUUUGG    79.2％    597    GAACUCUAUUCCAACAAAU    78.5％

544   UCAAUGAGAGGAAUAAGAG    79.2％    598    GGUCAGUGAAACACAGGGA    78.5％

545   UGAGAGGAAUAAGAGUCAG    79.2％    599    AGAUGUCAAUGAGAGGAAU    78.5％

546   CAAUGAGAGGAAUAAGAGU    79.2％    600    GAGAUGUCAAUGAGAGGAA    78.5％

547   GUGCCACAGCACACAAAUU    79.2％    601    AACUCUAUUCCAACAAAUG    78.5％

548   GAGGAAUAAGAGUCAGCAA    79.2％    602    GGGACAAGGAUGGUGGACA    78.4％

549   CCUGUAUUCAACUACAACA    79.2％    603    CAAACUCUAUGGAGUAAAA    78.4％

550   CAGCUCAUCCUUCAGCUUU    79.2％    604    GGACAAGGAUGGUGGACAU    78.4％

551   AAUGAGGGAAUAAGGAGUC    79.1％    605    ACAGCACACAAAUUGGCGG    78.4％

552   UGGAUUCAACUACAACAAG    79.1％    606    CACAGCACACAAAUUGGCG    78.4％

553   AGAGGAAUAAGAGUCAGCA    79.1％    607    CAAUACCUAUCAAUGGAUC    78.3％

554   CUAUCAAUGGAUCAUCAGA    79.1％    608    GACAAGGAUGGUGGACAUU    78.3％

555   GGUCAAUACCUAUCAAUGG    79.1％    609    AAACUCUAUGGAGUAAAAU    78.3％

556   GAGUCAGCAAAAUGGGUGU    79.1％    610    CAAAAUGGAAUUUGAACCA    78.1％

557   AUGAGAGGAAUAAGAGUCA    79.1％    611    UGUUGGAACAAAUGUAACA    78.1％

558   UGGUCAAUACCUAUCAAUG    79.1％    612    AACAAAAUGGAAUUUGAAC    78.1％

559   UCUCCUGUAUUCAACUACA    79.1％    613    AACUCUAUGGAGUAAAAUG    78.1％

560   AGAGUCAGCAAAAUAGGUG    79.1％    614    ACAAAAUGGAAUUUGAACC    78.1％

561   GCCACAGCACACAAAUUGG    79.1％    615    CACACAAAUUGGCGGGACA    78.1％

562   CUCCUGUAUUCAACUACAA    79.1％    616    GUUGGGAACAAAUGUACAC    78.1％

563   GUCAAUGAGAGGAAUAAGA    79.1％    617    GCACACAAAUUGGCGGGAC    78.0％

564   AGAGAUGUCAAUGAGAGGA    79.1％    618    CAGAAAGAUGCGAAAGUGC    78.0％

565   UGUCAAUGAGAGGAAUAAG    79.1％    619    AGCACACAAAUUGGCGGGA    78.0％

566   GGAUGGCCAUCAAUUAAUG    79.1％    620    AAAGAUGCGAAAGUGCUUU    78.0％

567   GAGAGGAAUAAGAGUCAGC    79.1％    621    AGAAAGAUGCGAAAGUGCU    78.0％

568   UGCCACAGCACACAAAUUG    79.1％    622    AAGAUGCGAAAGUGCUUUU    78.0％

569   GGAAUAAGAGUCAGCAAAA    79.0％    623    GCGGGACAAGGAUGGUGGA    78.0％

570   UACCUAUCAAUGGAUCAUC    79.0％    624    ACACAAAUUGGCGGGACAA    78.0％

571   UUGGCGGGACAAGGAUGGU    79.0％    625    UGAUGUCGCAGUCUCGCAC    77.9％

572   AUUGGCGGGACAAGGAUGG    79.0％    626    CAACAAAAUGGAAUUUGAA    77.9％

573   UCAAUACUACUCAAUGGAU    78.9％    627    GGAACAAAUGUACACUCCA    77.8％

574   AUGCAGACCUCAGUGCCAA    78.9％    628    CAAAUGUACACUCCAGGUG    77.8％

575   CAAGGACAAACUCUAUGGA    78.9％    629    CUGAUGUCGCAGUCUCGCA    77.8％

576   AAGGACAAACUCUAUGGAG    78.9％    630    CGGGACAAGGAUGGUGGAC    77.8％

577   AGGAAUAAGAGUCAGCAAA    78.9％    631    GGGAACAAAUGUACACUCC    77.8％

578   GAGUUCACAAUGGUGGGGA    78.9％    632    UUGGGAACAAAUGUACACU    77.8％

579   AAUAAGAGUCAGCAAAAUG    78.9％    633    GAACAAAUGACUACUCCAG    77.8％

580   AGUUCACAAUGUGUGGGAA    78.9％    634    AAAUGGUCACAUCCAGUGG    77.8％

581   GAAUAAGAGUCAGCAAAAU    78.9％    635    GAAAGAUGCGAAAGUGCUU    77.8％

582   AUGUCAAUGAGAGGAAUAA    78.9％    636    UGGGAACAAAUGUACACUC    77.8％

583   UUGGUCAAUACCUAUCAAU    78.9％    637    ACAAAUGUACACUCCAGGU    77.8％

584   GUUCACAAUGGUGGGGAAA    78.9％    638    GAGUAGACAUAAACCCUGG    77.8％

585   UCCUGUAUUCAACUACAAC    78.9％    639    AACAAAUGUACACUCCAGG    77.8％

586   UUCUCCUGUAUUCAACUAC    78.8％    640    AGAGUAGACAUAAACCCUG    77.8％

587   CAUGCAGACCUCAGUGCCA    78.8％    641    AUUUUAGAAAUCAAGUCAA    77.7％

588   UGAGGAAUGACGAUGUUGA    78.7％    642    AAGAGUAGACAUAAACCCU    77.7％

643   CAUUUUAGAAAUCAAGUCA    77.7％    697   GAUAAUAAAGCUUCUCCCU    76.9％

644   GAAGAGUAGACAUAAACCC    77.7％    698   AAAGCUUCUCCCUUUUGCA    76.9％

645   UGAAAGACCCAGAUGAAGC    77.7％    699   AUAAAGCUUCUCCCUUUUG    76.9％

646   GGCGGGACAAGGAUGGUGG    77.7％    700   GAACCAUUUCAAUCUUUAG    76.8％

647   AAGACCCAGAUGAAAGCAC    77.7％    701   AGUAGACAUAAACCCUGGU    76.8％

648   AAUGUACACUCCAGGUGGA    77.6％    702   CUCAUCCUUCAGCUUUGGU    76.8％

649   GAUGUCGCAGUCUCGCACU    77.6％    703   UCAUCCUUCAGCUUUGGUG    76.8％

650   UGGCGGGACAAGGAUGGUG    77.6％    704   UGAACCAUUUCAAUCUUUA    76.8％

651   GAAGACCCAGAUGAAAGCA    77.6％    705   AACCAUUUCAAUCUUUAGU    76.8％

652   CAUUUUCAGAAAGAUGCGA    77.5％    706   UUUGAACCAUUUCAAUCUU    76.8％

653   UUUUCAGAAAGAUGCGAAA    77.5％    707   UUGAACCAUUUCAAUCUUU    76.8％

654   AUUUUCAGAAAGAUGCGAA    77.5％    708   UUCUCCCUUUUGCAGCCGC    76.8％

655   AGACCACUAAAAGACUAAC    77.4％    709   CAUCCUUCAGCUUUGGUGG    76.8％

656   UUUCAGAAAGAUGCGAAAG    77.4％    710   CUUCUCCCUUUUGCAGCCG    76.8％

657   AAGACCACUAAAAGACUAA    77.4％    711   GUAUAUACAUUGAAGUUUU    76.7％

658   AUUGAAAGACCCAGAUGAA    77.4％    712   GGAACAAGCAGUAUAUACA    76.7％

659   AACAAGGCCACUAAAAGAC    77.4％    713   GAAUUUGAACCAUUUCAAU    76.7％

660   ACAAGACCACUAAAAGACU    77.4％    714   UCUCCCUUUUGCAGCCGCU    76.7％

661   CAGCACACAAAUUGGCGGG    77.4％    715   CUCCCUUUUGCAGCCGCUC    76.7％

662   AGACCCAGAUGAAAGCACA    77.4％    716   UCCCUUUUGCAGCCGCUCC    76.7％

663   GACCACUAAAAGACUAACA    77.4％    717   GGAAUUUGAACCAUUUCAA    76.7％

664   UUCAGAAAGAGCGGAAAGU    77.4％    718   AGUAUAUACAUUGAAGUUU    76.7％

665   GUAGACAUAAACCCUGGUC    77.3％    719   AUUUGAACCAUUUCAAUCU    76.7％

666   ACCCAGAUGAAAGCACAUC    77.3％    720   AAUUUGAACCAUUUCAAUC    76.7％

667   UAGACAUAAACCCUGGUCA    77.3％    721   GAACAAGCAGUAUAUACAU    76.7％

668   CAAGACCACUAAAAGACUA    77.2％    722   GCUUCUCCCUUUUGCAGCC    76.7％

669   UGGUCAUGCAGACCUCAGU    77.2％    723   AACAAGCAGUAUAUACAUU    76.5％

670   GGUCAUGCAGACCUCAGUG    77.2％    724   CCUUUUGCAGCCGCUCCAC    76.4％

671   UCAGAAAGAUGCGAAAGUG    77.2％    725   ACAAACUCUAUGGAGUAAA    76.4％

672   GCACAUCCGGAGUGGAGUC    77.2％    726   GGACAAACUCUAUGGAGUA    76.4％

673   GUCAUGCAGACCUCAGUGC    77.2％    727   GACAAACUCUAUGGAGUAA    76.4％

674   GACCCAGAUGAAAGCACAU    77.2％    728   CAGGAUACUAACAUCAGAA    76.4％

675   GUGUUGGGAACAAAUGUAC    77.1％    729   AGGACAAACUCUAUGGAGU    76.4％

676   AGCAGUAUAUACAUUGAAG    77.1％    730   AACGUGUUGGGAACAAAUG    76.4％

677   GUGGUGGUUAGCAUUGAUC    77.1％    731   GCCAGGAUACUAACAUCAG    76.4％

678   AGCUUCUCCCUUUUGCAGC    77.1％    732   AGGAACGUGUUGGGAACAA    76.4％

679   UGGUGGUUAGCAUUGAUCG    77.1％    733   GAACGUGUUGGGAACAAAU    76.4％

680   GGAUACUAACAUCAGAAUC    77.1％    734   CCAGGAUACUAACAUCAGA    76.4％

681   CGUGUUGGGAACAAAUGUA    77.1％    735   CUUUUGCAGCCGCUCCACC    76.4％

682   AAGCUUCUCCCUUUUGCAG    77.1％    736   CAGUAUAUACAUUGAAGUU    76.4％

683   GCAGUAUAUACAUUGAAGU    77.1％    737   GGAACGUGUUGGGAACAAA    76.4％

684   ACGUGUUGGGAACAAAUGU    77.1％    738   UUUUGCAGCCGCUUCCACA    76.4％

685   AAGCAGUAUAUACAUUGAA    77.0％    739   AGAUGCGAAAGUGCUUUUU    76.3％

686   AGGAUACUAACAUCAGAAU    77.0％    740   GGCCAUUAGAGGCCAAUAC    76.2％

687   GCAUUUUCAGAAAGAUGCG    77.0％    741   AGGCCAUUAGAGGCCAAUA    76.2％

688   ACAAGCAGUAUAUACAUUG    77.0％    742   CCCUUUUGCAGCCGCUCCA    76.2％

689   UCAUGCACACCUCAGUGCC    77.0％    743   UUAGAGGCCAAUACAGUGG    76.2％

690   CAAGCAGUAUAUACAUUGA    77.0％    744   AAGGCCAUUAGAGGCCAAU    76.1％

691   AGACAUAAACCCUGGUCAU    77.0％    745   CCAUUAGAGGCCAAUACAG    76.1％

692   AAUAAAGCUUCUCCCUUUU    76.9％    746   AUUAGAGGCCAAUACAGUG    76.1％

693   UAAAGCUUCUCCCUUUUGC    76.9％    747   GCCAUUAGAGGCCAAUACA    76.1％

694   AUAAUAAAGCUUCUCCCUU    76.9％    748   UCAGCAGAUCCACUAGCAU    75.9％

695   UAAUAAAGCUUCUCCCUUU    76.9％    749   GUAUCAGCAGAUCACUAAG    75.9％

696   CACAAAUUGGCGGGGACAAG   76.9％    750   CAAAAUUCAAUGGUCUCAG    75.9％

751   UAUCAGCAGAUCCACUAGC    75.9％    805   GGGUGGUGGUUAGCAUUGA  74.7％

752   CAGCAAUCCACUUAGCAUC    75.9％    806   AGUAUCAGCAGAUCCACUA  74.7％

753   CAUUAGAGGCCAAUACAGU    75.9％    807   CAGUAUCAGCAGAUCCACD  74.7％

754   GUCAAAAUUCAAUGGUCUC    75.8％    808   AUUAAGCAUCAAUGAACUG  74.7％

755   UCAAAAUUCAAUGGUCUCA    75.8％    809   AGGGUGGUGGUUAGCAUUG  74.7％

756   GGAUCAUCAGAAAUUGGGA    75.8％    810   AGAACUCCGAGAUUGCAAA  74.7％

757   UGGAUCAUCAGAAAUUGGG    75.8％    811   GAACUCCGAGAUUGCAAAA  74.7％

758   GAUCAUCAGAAAUUGGGAA    75.7％    812   GACAGAAGAUACGGACCAG  74.6％

759   AGCAGAUCCACUAGCAUCU    75.7％    813   ACAGAAGAUACGGACCAGC  74.6％

760   UUGAAGACCCAGAUGAAAG    75.6％    814   CAGAACUCUAUUCCAACAA  74.6％

761   ACUCUAUGGAGUAAAAUGA    75.6％    815   CAGAAUGCAGUUCUCUUCA  74.6％

762   AGGAAGACAGAAGAUACGG    75.6％    816   GCAGUAUCAGCAGAUCCAC  74.6％

763   AUCAGCAGAUCCACUAGCA    75.6％    817   GGUGGUGGUUAGCAUUGAU  74.6％

764   UGUCAAAAUUCAAUGGUCU    75.6％    818   CUCCGAGAUUGCAAAAUUU  74.6％

765   AAGGAAGACAGAAGAUACG    75.6％    819   UCCGAGAUUGCAAAAUUUC  74.6％

766   CAAUGGAUCAUCAGAAAUU    75.5％    820   CAGAAGAUACGGACCAGCA  74.6％

767   CCCUGGUCAUGCAGACCUC    75.5％    821   GAAGACAGAAGAUACGGAC  74.5％

768   AAUGGAUCAUCAGAAAUUG    75.5％    822   AGCCAGGAUACUAACAUCA  74.5％

769   AUGGAUCAUCAGAAAUUGG    75.5％    823   ACUCCGAGAUUGCAAAAUU  74.5％

770   AAAGCAGAAAUGCAGUCUC    75.4％    824   GAGGGUGGUGGUUAGCAUU  74.5％

771   UUUGUCAGAACUCUAUUCC    75.4％    825   AAGACAGAAGAUACGGACC  74.5％

772   UUGUCAGAACUCUAUUCCA    75.4％    826   GGAAGACAGAAGAUACGGA  74.5％

773   CAAAGCAGAAUGCAGUUCU    75.4％    827   ACCAACGUGGGAAUGUAUU  74.4％

774   UCAAUGGAUCAUCAGAAAU    75.3％    828   AGACAGAAGAUACGGACCA  74.4％

775   CUCCACCAAAGCAAAGCAG    75.3％    829   CGAGAUUGCUAAAUUUCUC  74.4％

776   GCUCCACCAAAGCAAAGCA    75.3％    830   CCGAGAUUGCAAAAUUUCU  74.4％

777   UAAGCAUCAAUGAACUGAG    75.3％    831   UUAAGCAUCAAUGAACUGA  74.4％

778   UCUAUGGAGUAAAAUGAGU    75.3％    832   GACCAACGUGGGAAUGUAU  74.4％

779   UCAGAACUCUAUUCCAACA    75.2％    833   UAAAUGUGAGGGGAUCAGG  74.2％

780   GAGCCAGGAUACUAACAUC    75.2％    834   UGACUGUAAAUGUGAGGGG  74.1％

781   GCAGAAUGCAGUUCUCUUC    75.2％    835   UGGUGGGGAAAUGAGCAAC  74.1％

782   GAGAGGGUGGUGGUUAGCA    75.2％    836   GUUGCUGGCGGAACAAGCA  74.1％

783   GGAGCCAGGAUACUAACAU    75.2％    837   UUGCUGGCGGAACAAGCAG  74.1％

784   CUGUCAAAAUUCAAUGGUC    75.2％    838   CCAGUUGCUGGCGGAACAA  74.0％

785   CAUUAAGCAUCAAUGAACU    75.2％    839   CACAAGAUGUAAUUAUGGA  74.0％

786   AGCAGAAUGCAGUUCUCUU    75.2％    840   ACAAGAUGUAAUUAUGGAA  74.0％

787   AGAGGGUGUGGGUUAGCAU    75.2％    841   AGGCACAAGAUGUAAUUAU  74.0％

788   AAGCAGAAUGCAGUUCUCU    75.2％    842   GCACAGAAGAUGAAUAUGG  74.0％

789   CUCUAUGGAGUAAAAUGAG    75.2％    843   AAGAUGUAAUUAUGGAAGU  74.0％

790   CGCUCCACCAAAGCAAAGC    75.2％    844   AGAUGUAAUUAUGGAAGUU  74.0％

791   GUCAGAACUCUAUUCCAAC    75.2％    845   GUAAAUGUGAGGGGAUCAG  74.0％

792   GCAUUAAGCAUCAAUGAAC    75.2％    846   GGCACAAGGAUAAAUUAUG  74.0％

793   AGCACAUCCGGAGUAGAGU    75.2％    847   AACCUUUGCAAAAGGGAAA  74.0％

794   CAGAGAGGGUGGUGGUUAG    75.1％    848   ACCUUGCAAAAGGGGAAAA  74.0％

795   UGGGAGCCAGGAUACUAAC    75.1％    849   CAGUUGCUGGCGGAACAAG  74.0％

796   ACAGAGGGGUGGUGGGUUA    75.1％    850   GAGGCACAAGAUGUAAUUA  74.0％

797   AGAGAGGGUGGUGGUUAGC    75.1％    851   CAGAUGAAAGCACAUCCGG  73.9％

798   GUGGGAGCCAGGAUACUAA    75.1％    852   UUUCUCCCAGUUGCUGGCG  73.9％

799   UGUCAGAACUCUAUUCCAA    75.1％    853   CUCCCAGUUGCUGGCGGAA  73.9％

800   GAAGAACUCCGAGAUUGCA    74.9％    854   GGCGGAACAAGCAGUAUAU  73.9％

801   GGGAGCCAGGAUACUAACA    74.8％    855   AUGGUGGGGAAAAGAGCAA  73.9％

802   AACUCCGAGAUUGCAAAAU    74.8％    856   UUCUCCCAGUUGCUGGCGG  73.9％

803   AAGAACUCCGAGAUUGCAA    74.8％    857   UACAAGACUUAUUUUGACA  73.9％

804   GAGAUUGCAAAAUUUCUCC    74.7％    858   AAAUGUGAGGGGAUCAGGG  73..9％

859    ACAAGACUUAUUUUGACAA    73.9％    913   UGAAUACUCCAGUACAGAG    73.2％

860    CAAGACUUAUUUUGACAAA    73.9％    914   CAAAUUGGCGGGACAAGGA    73.2％

861    UCCCAGUUGCUGGCGGAAC    73.9％    915   AAUACAGUGGGUUUGUCAG    73.2％

862    GCGGAACAAGCAGUAUAUA    73.9％    916   CAAUACAGUGGGUUUGUCA    73.2％

863    AUUUUCUCCAGUUGCUGGC    73.9％    917   AAUUGGCGGGACAAGGAUG    73.2％

864    CAAGAUGUAAUUAUGGAAG    73.9％    918   UAGGUAAGGAAGACAGAAG    73.2％

865    AUAUGACUCCAAGCACAGA    73.8％    919   CAAUGAAGUGGGAGCCAGG    73.2％

866    CGGAACAAGCAGUAUAUAC    73.8％    920   AGAUGAAAGCACAUCCGGA    73.2％

867    GAUAUGACUCCAAGCACAG    73.8％    921   CCAAUACAGUGGGUUUGUC    73.2％

868    AGUUGCUGGCGGAACAAGC    73.8％    922   GGUAAGGAAGACAGAAGAU    73.2％

869    UUGAGAAUCAGCUCAUCCU    73.8％    923   GUAAGGAAGACAGAAGAUA    73.2％

870    AAAAGAGCAACAGCUAUAC    73.8％    924   GGUGGGGAAAAGAGCAACA    73.1％

871    AAAGAGCAACAGCUAUACU    73.8％    925   GUAUGGAAAGAAUAAAAGA    73.1％

872    CCAGAUGAAAGCACAUCCG    73.8％    926   AAUACUCCAGUACAGAGAG    73.1％

873    CCCAGUUGCUGGCGGAACA    73.8％    927   ACAAAUUGGCGGGACAAGG    73.1％

874    GACUGUAAAUGUGAGGGGA    73.8％    928   GGAAAAGAGCAACAGCUAU    73.0％

875    CUGGCGGAACAAGCAGUAU    73.8％    929   GUGGAUGAAUACUCCAGUA    73.0％

876    ACUGUAAAUGUGAGGGGAU    73.8％    930   UGGAUGAAUACUCCAGUAC    73.0％

877    UGGCGGAACAAGCAGUAUA    73.8％    931   GAAAAGAGCAACAGCUAUA    73.0％

878    UGUAAAUGUGAGGGGAUCA    73.8％    932   GGAUGAAUACUCCAGUACA    73.0％

879    CUGUAAAUGUGAGGGGAUC    73.8％    933   AGGUAAGGAAGACAGAAGA    73.0％

880    GAAAGCACAUCCGGAGUGG    73.7％    934   GGCAAGGAGACGUGGUGUU    73.0％

881    AAAGCACAUCCGGAGUGGA    73.7％    935   GGGAAAAGAGCAACAGCUA    73.0％

882    UGCUGGCGGAACAAGCAGU    73.7％    936   UAAGGAAGACAGAAGAUAC    72.9％

883    GAAGUGGGAGCCAGGAUAC    73.7％    937   GACCAGCAUUAAGCAUCAA    72.9％

884    AAGUGGGAGCCAGGAUACU    73.7％    938   UAUUCCAACAAAUGAGAGA    72.9％

885    CCAACGUGGGAAUGUAUUA    73.7％    939   GGACCAGCAUUAAGCAUCA    72.9％

886    GCUGGCGGAACAAGCAGUA    73.7％    940   UAUGACUCCAAGCACAGAG    72.9％

887    AGUGGGAGCCAGGAUACUA    73.7％    941   GGUGUGGAUGAAUACUCCA    72.8％

888    AAGACUUAUUUUGACAAAG    73.6％    942   UGGAAGUUGUUUUUCCCAA    72.8％

889    UGAAAGCACAUCCGGAGUG    73.6％    943   GUGACAUGGUGGAAUAGAA    72.8％

890    UGGCCAUGGUGUUUUCACA    73.6％    944   AUGGAAGUUGUUUUUCCCA    72.8％

891    GUGGCCAUGGUGUUUUCAC    73.6％    945   ACCAGCAUUAAGCAUCAAU    72.8％

892    AUGAAUACUCCAGUACAGA    73.5％    946   UGACAUGGUGGAAUAGAAA    72.8％

893    AUGAAGUGGGAGCCAGGAU    73.5％    947   AACAAGAUUUCUCCCAGUU    72.8％

894    AAUAAGUGGGAGCCAGGGA    73.5％    948   GGGGAAAAGAGCAACAGCU    72.8％

895    CCCAAUGAAGUGGGAGCCA    73.5％    949   GAAGUUGUUUUUCCCAAUG    72.8％

896    UGAAGUGGGAGCCAGGAUA    73.5％    950   GGAAAGUUGUUUUCCCAAU    72.8％

897    GGAACAUAGUAAGAAGAGC    73.5％    951   AAGUUGUUUUUCCCAAUGA    72.8％

898    AGGAACAUAGUAAGAAGAG    73.5％    952   GGGUGUGGAUGAAUACUCC    72.8％

899    AAGCACAUCCGGAGUGGAG    73.5％    953   CAAUAGCCGAAGCAAUAAU    72.7％

900    CCCAGAUGAAAGCACAUCC    73.5％    954   UCAAUAGCCGAAGCAAUAA    72.7％

901    AUGAAAGCACAUCCGGAGU    73.5％    955   AAAACAAGAUUUCUCCCAG    72.7％

902    UCUCCCAGUUGCUGGCGGA    73.5％    956   GAAAAACAAGAUUUCUCCC    72.7％

903    GAUGAAAACUCCAGUACAG    73.5％    957   AAACAAGUUUCUCCCAGGU    72.7％

904    AGACUUAUUUUGACAAAGU    73.3％    958   GUGUGGAUGAAUACUCCAG    72.7％

905    CCAAUGAAGUGGGAGCCAG    73.3％    959   ACAAGAUUUCUCCCAGUUG    72.7％

906    AUGGCCAUCAAUUAAUGUU    73.3％    960   CAAGAUUUCUCCAGUUGGC    72.7％

907    UGGGGAAAGGAGCAACAGC    73.2％    961   UGGGUGUGGAUGAAUACUC    72.7％

908    GAAUACUCCAGUACAGAGA    73.2％    962   UUCAUUUUAGAAAUCAAGU    72.6％

909    GAUGAAAGCACAUCCGGAG    73.2％    963   CAGUCAAUAGCCGAAGCAA    72.6％

910    GUGGGGGAAAGAGCAACAG    73.2％    964   AUACAGUGGGUUUGUCAGA    72.6％

911    AAAUUGACGGGACAAGGAU    73.2％    965   ACAGUGGGUUUGUCAGAAC    72.6％

912    GGCCAUGGUGUUUUCACAA    73.2％    966   GUCAAUAGCCGAAGCAAUA    72.6％

967   UACAGUGGGUUUGUCAGAA    72.6％    1021   CUUGAUGGUUGCAUACACU    72.2％

968   AAGAUUUCUCCCAGUUGCU    726％     1022   AGCAAAAUGGGUGUGGAUG    72.2％

969   GUUCAUUUUAGAAAUCAAG    72.6％    1023   CCACCAAAGCAAAGCAGAA    72.2％

970   GGGCAAGGAGACGUGGUGU    72.6％    1024   AAAGAAGAACUCCGAGAUU    72.2％

971   AUGGGUGUGGAUGAAUACU    72.6％    1025   UAUUACCAGAUAUGACUCC    72.1％

972   UCAUUUUAGAAAUCAAGUC    72.6％    1026   CAGCAAAAUGGGUGUGGAU    72.1％

973   UUCAGCUCAUAGUGAGUGG    72.5％    1027   UGGUUCAGCUCAUAGUGAG    72.1％

974   CCAGAUAUGACUCCAAGCA    72.5％    1028   GUUCAGCUCAUAGUGAGUG    72.1％

975   CAAAGCAAAGCAGAAUGCA    72.5％    1029   AAGAGUCAGCAAAAUGGGU    71.1％

976   AGUCAAUAGCCGAAGCAAU    72.5％    1030   GUCAGCAAAAUGGGUGUGG    72.1％

977   CCAAAGCAAAGCAGAAUGC    72.5％    1031   UCAGCAAAAUGGGUGUGGA    72.1％

978   UACAACAAGACCACUAAAA    72.4％    1032   ACCUGAAUUUCGUCAACAG    71.0％

979   AGAAAUCAAGUCAAGAUAC    72.4％    1033   CUCCCUUGAUGGUUGCAUA    72.0％

980   AGCAAAGCAGAAUGCAGUU    72.4％    1034   CUAUUCCAACAAAUGAGAG    72.0％

981   CAGAUAUGACUCCAAGCAC    72.4％    1035   UCCCUUGAUGGUUGCAUAC    72.0％

982   GUAAAUGAAGUGAUGCUGG    72.4％    1036   UCUCCCUUGAUGGUUGCAU    72.0％

983   GAAAUCAAGUCAAGAUACG    72.4％    1037   GGUUCAGCUCAUAGUGAGU    72.0％

984   UUAUGGAAGUUGUUUUUCC    72.4％    1038   AUUACCAGAUAUGACUCCA    72.0％

985   CAACAAGACCACUAAAAGA    72.4％    1039   CAUCCGGAGUGGAGUCCGC    72.0％

986   AAAGCAAAGCAGAAUGCAG    72.4％    1040   GACCUGAAUUUCGUCAACA    72.0％

987   UACCAGAUAUGACUCCAAG    72.4％    1041   UUGGUUCAGCUCAUAGUGA    72.0％

988   AGAUAUGACUCCAAGCACA    72.4％    1042   CCAAAAGUAUACAAGACUU    71.9％

989   AUUAUGGAAGUUGUUUUUC    72.4％    1043   ACUGAAGAACAAGCUGUGG    71.9％

990   ACAACAAGACCACUAAAAG    72.4％    1044   CUGAAGAACAAGCUGUGGA    71.9％

991   AAGCAAAGCAGAAUGCAGU    72.4％    1045   CAAAAGUAUACAAGACUUA    71.9％

992   GAGUAAAAUGAGUGAUGCU    72.4％    1046   AUUGGGAAGCUGUCAAAAU    71.9％

993   AGUAAAAUGAGUGAUGCUG    72.4％    1047   AAAGAUGCCGGCACUUUAA    71.9％

994   ACCAGAUAUGACUCCAAGC    72.4％    1048   AUUGGUUCAGCUCAUAGUG    71.9％

995   UGUGGAUGAAUACUCCAGU    72.4％    1049   UCAAGAACAAGCUGUGGAU    71.9％

996   AAAAACAAGAUUUCUCCCA    72.4％    1050   AAUUGGGAAGCUGUCAAAA    71.9％

997   GCAAAGCAGAAUGCAGUUC    72.3％    1051   AGUCAGCAAAAUGGGUGUG    71.7％

998   GAUUGGUUCAGCUCAUAGU    72.3％    1052   ACAUCCGGAGUGGAGUCCG    71.7％

999   UUUUAGAAAUCAAGUCAAG    72.3％    1053   UGCAAAAUUUCUCCCUUGA    71.7％

1000  UAUGGAAGUUGUUUUUCCC    72.3％    1054   AAAAUUUCUCCCUUGAUGG    71.7％

1001  AGAUUGGUUCAGCUCAUAG    72.3％    1055   UUUUGGUCAAUACCUAUCA    71.7％

1002  AAUGGGUGUGGAUGAAUAC    72.3％    1056   GCAAAAUUUCUCCCUUGAU    71.7％

1003  UUUAGAAAUCAAGUCAAGA    72.3％    1057   CAAAAUUUCUCCCUUGAUG    71.7％

1004  CUACAACAAGACCACUAAA    72.3％    1058   CACAAUGGUGGGGAAAAGA    71.7％

1005  UAGAAAUCAAGUCAAGAUA    72.3％    1059   AAAUUUCUCCCUUGAUGGU    71.7％

1006  UUAGAAAUCAAGUCAAGAU    72.3％    1060   GAGUUCGAGACCAACGUGG    71.6％

1007  UUACCAGAUAUGACUCCAA    72.3％    1061   AUUUCUCCUUGAUGGUUUG    71.6％

1008  ACCAAAGCAAAGCAGAAUG    72.2％    1062   UGUUGGUAAUGAAACGAAA    71.6％

1009  ACAAUGGUGGGGAAAAGAG    72.2％    1063   UAUACAAGACUUAUUUUGA    71.6％

1010  CAAUGGUGGGGAAAAGAGC    72.2％    1064   UGGGAAGCUGUCAAAAUUC    71.6％

1011  CCCUUGAUGGUUGCAUACA    72.2％    1065   GAGAGUUCGAGACCAACGU    71.6％

1012  CACCAAAGCAAAGCAGAAU    72.2％    1066   AAAUUGGGAAGCUGUCAAA    71.6％

1013  AAUUGGUGGGGAAAGAGCA    72.2％    1067   AGUAUACAAGACUUAUUUU    71.6％

1014  AAAUGGGUGUGGAUGAAUA    72.2％    1068   GUGUUGGUAAUGAAACGAA    71.6％

1015  CAAAAUGGGUGUGGAUGAA    72.2％    1069   AAGUAUACAAGACUUAUUU    71.6％

1016  AAAAUGGGUGUGGAUGAAU    72.2％    1070   AAAGUAUACAAGACUUAUU    71.6％

1017  AAGAAGAACUCCGAGAUUG    72.2％    1071   AGAGUUCGAGACCAACGUG    71.6％

1018  GCAAAAUGGUUGUGGAUGA    72.2％    1072   GAAAAGAUGCCGGCACUUU    71.6％

1019  CCUUGAUGGUUGCAUACAU    72.2％    1073   UUCUCCCUUGAUGGUUGCA    71.6％

1020  AGAAGAACUCCGAGAUUGC    72.2％    1074   GGAAAAGAUGCCGGCACUU    71.6％

1075   GUAUACAAGACUUAUUUUG    71.6％    1129   CUGAGUCGGUUUUGGUCAA    71.2％

1076   UUGGGAAGCUGUCAAAAUU    71.6％    1130   AGUCGGUUUUGGUCAAUAC    71.2％

1077   GGGAAGCGCUCAAAAUUCA    71.6％    1131   GAGUCGGUUUUGGUCAAUA    71.2％

1078   AGAUUGCAAAAUCUCUCCC    71.6％    1132   CAGAAAUUUGGGAAAGCUC    71.1％

1079   GUUGGUAAUGAAACGAAAA    71.6％    1133   UUUUCCCAAUGAAGUGGGA    71.1％

1080   UUUCUCCCUUGAUGGUUGC    71.6％    1134   UUCCCAAUGAAGUGGGAGC    71.1％

1081   AAUUAUGGAAGUUGUUUUU    71.5％    1135   UUCCCAAUGAAGUGGGAGC    71.1％

1082   UGUUUUUCCCAAUGAAGUG    71.5％    1136   AGACCAACGUGGGAAUGUA    71.0％

1083   AUUGCAAAAUUUCUCCCUU    71.5％    1137   AAGAUGCCGGCACUUUAAU    71.0％

1084   UUUUUCCCAAUGAAGUGGG    71.5％    1138   UGAGUCGGUUUUGGUCAAU    71.0％

1085   GUUUUUCCCAAUGAAGUGG    71.5％    1139   AAAUCAAGUCAAGAUACGC    71.0％

1086   AAUUUCUCCCUUGAUGGUU    71.5％    1140   CGGUUUUGGUCAAUACCUA    71.0％

1087   UUCUCGGAAAAGAUGCCGG    71.5％    1141   UCGGUUUUGGUCAAUACCU    71.0％

1088   UUUGGUCAAUACCUAUCAA    71.5％    1142   CGAGACCAACGUGGGAAUG    71.0％

1089   GAUUGCAAAAUUUCUCCCU    71.5％    1143   GAGACCAACGUGGGAAUGU    71.0％

1090   AAAAGUAGACAAGACUUAU    71.5％    1144   AGGAUGCCGGCACUUAAUU    71.0％

1091   ACCCAAAAGUAUACAAGAC    71.5％    1145   GAUGCCGGCACUUUUAUUG    70.9％

1092   GUUUUGGUCAAUUACUAUC    71.5％    1146   AUGCCGGCACUUUAAUUGA    70.9％

1093   CACAUCCGGAGUGGAGUCC    71.5％    1147   UGCCGGCACUUUAAUUGAA    70.9％

1094   UUGUUUUUCCCAAUGAAGU    71.5％    1148   GCCGGCACUUUAAUUGAAG    70.8％

1095   GAAAUUGGGAAGCUGUCAA    71.4％    1149   UGAGGAGUUCACAAUGGUG    70.8％

1096   CGGAAAAGAUGCCGGCACU    71.4％    1150   CCGGCACUUUAAUUGAAGA    70.8％

1097   UCCACCAAAGCAAAGCAGA    71.4％    1151   AGUUCGAGACCAACGUGGG    70.8％

1098   AGAAAUUGGGAAGCUGUCA    71.4％    1152   AAUGUAUUAUUAUCUCCUG    70.8％

1099   AAGCUGUCAAAAUUCAAUG    71.4％    1153   UCAUCAGAAAUUGGGAAGC    70.8％

1100   UAUGAGGAGUUCACAAUGG    71.4％    1154   UUCGAGACCAACGUGGGAA    70.8％

1101   UCGGAAAAGAUGCCGGCAC    71.4％    1155   AUCAUCAGAAAUUGGGAAG    70.8％

1102   GGAAGCUGUCAAAAUUCAA    71.4％    1156   AUGUAUUAUUAUCUCCUGA    70.8％

1103   GCUGUCAAAAUUCAAUGGU    71.4％    1157   UCGAGACCAACGUGGGAAU    70.8％

1104   AUGAGGAGUUCACAAUGGU    71.4％    1158   GUUCGAGACCAACGUGGGA    70.8％

1105   GAAGCUGUCAAAAUUCAAU    71.4％    1159   GGUUUUGGUCAAUACCUAU    70.8％

1106   AGUUGUUUUUCCCAAUGAA    71.4％    1160   GGAAUGUAUUAUUAUCUCC    70.7％

1107   GUUGUUUUUCCCAAUGAAG    71.4％    1161   GGGAUGUAUUAUUAAUCUC    70.7％

1108   UUGCAAAAUUUCUCCCUUG    71.4％    1162   CAUCAGAAAUUGGGAAGCU    70.7％

1109   AGCUGUCAAAAUUCAAUGG    71.4％    1163   UCCCAAUGAAGUGGGAGCC    70.6％

1110   CUCGGAAAAGAUGCCGGCA    71.4％    1164   UAAGGCCAUUAGAGGCCAA    70.6％

1111   GAACAGUCAAUAGCCGAAG    71.3％    1165   GUCGGUUUUGGUCAAUACC    70.6％

1112   UACCCAAAAGUAUACAAGA    71.3％    1166   GGUCCUGAGUCGGUUUUGG    70.6％

1113   UCAAUGAUGUGGGAGAUUA    71.3％    1167   GUCCUGAGUCGGUUUUGGU    70.6％

1114   AAAAGAUGCCGGCACUUUA    71.3％    1168   CUAAGGCCAUUAGAGGCCA    70.6％

1115   GACAUGGUGGAAUAGAAAU    71.3％    1169   CCUAAGGCCAUUAGAGGCC    70.6％

1116   CAAUGAUGUGGGAGAUUAA    71.3％    1170   CGGCACUUUAAUUGAAGAC    70.6％

1117   GAAUAAAAGAACUACGGAA    71.3％    1171   ACAGUCAAUAGCCGAAGCA    70.5％

1118   AUCAGAAAUUGGGAAGCUG    71.3％    1172   UUCUCAUUAUAGGUAAGGA    70.3％

1119   GUGACCUGAAUUUCGUCAA    71.3％    1173   UCCUGAGUCGGUUUUGGUC    70.3％

1120   AGGUGACCUGAAUUUCGUC    71.3％    1174   CUCAUUACAGGUAAGGAAG    70.3％

1121   GGUGACCUGAAUUUCGUCA    71.3％    1175   UCAUUAUUAGGUAAGAAGA    70.3％

1122   UCAGAAAUUGGGAAGCUGU    71.2％    1176   UUUCUCAUUAUAGGUAAGG    70.3％

1123   UGACCUGAAUUUCGUCAAC    71.2％    1177   GAAUGUAUUAUUAUCUCCU    70.1％

1124   CCCAAAAGUAUACAAGACU    71.2％    1178   UCUCAUUAUAGGUAAGGAA    70.1％

1125   AUACAAGACUUAUUUUGAC    71.2％    1179   GAUCAGAUCGAGUGAUGGU    70.1％

1126   UCUCGGAAAAGAUGCCGGC    71.2％    1180   GGAUCAGAUCGAGUGAUGG    70.1％

1127   CCUGAGUCGGUUUUGGUCA    71.2％    1181   AUGGGAAUGGUUGGAGUAU    70.0％

1128   AACAGUCAAUAGCCGAAGC    71.2％    1182   UGGGAAUGGUUGGAGUAUU    70.0％

表2-2在表1-2所列甲型流感片段2(PB1)序列中以至少70％存在的保守19-mer序列

Seq ID        序列            百分比    1237    GAUCAUGAAGAUCUGUUCC    88.0％

1183   AUGAUGAUGGGCAUGUUCA    96.7％    1238    AGUGAAUGCACCAAAUCAU    88.0％

1184   UGAUGAUGGGCAUGUUCAA    96.7％    1239    GGAAUUCUUGAGGAUGAAC    88.0％

1185   AUCUGUUCCACCAUUGAAG    91.1％    1240    GGCCAUGGUGUCUAGGGCC    87.9％

1186   UCUGUUCCACCAUUGAAGA    91.1％    1241    AUCAUGAGGGAAUACAAGC    87.9％

1187   GAUCUGUUCCACCAUUGAA    90 9％    1242    CAUAGUGAAUGCACCAAAU    87.9％

1188   GAAGAUCUGUUCCACCAUU    90.8％    1243    CCUCCAUACAGCCAUGGAA    87.8％

1189   AAGAUCUGUUCCACCAUUG    90.7％    1244    AUACAAGCAGGAGUGGAUA    87.8％

1190   UGAAGAUCUGUUCCACCAU    90.1％    1245    CUCCAUACAGCCAUGGAAC    87.8％

1191   AGAUCUGUUCCACCAUUGA    90.7％    1246    AAUCAUGAGGGAAUACAAG    87.6％

1192   UGAUAAACAAUGACCUUGG    90.5％    1247    UCCAUACAGCCAUGGAACA    87.6％

1193   AUGAUAAACAAUGACCUUG    90.5％    1248    UACAAGCAGGAGUGGAUAG    87.6％

1194   CCAUACAGCCAUGGAACAG    89 2％    1249    UGUUCUCAAACAAAAUGGC    87.5％

1195   CAUACAGCCAUGGAACAGG    89.2％    1250    AUGUUCUCAAACAAAAUGG    87.5％

1196   GAGGCCAUGGUGUCUAGGG    89.1％    1251    UCACACAAAGAACAAUAGG    87.5％

1197   AGGCCAUGGUGUCUAGGGC    89.1％    1252    AUGGUCACACAAAGAACAA    87.4％

1198   GGAGGCCAUGGUGUCUAGG    89.0％    1253    UACACCAUGGACACAGUCA    87.4％

1199   UGGAGGCCAUGGUGUCUAG    88.9％    1254    UGGUCACACAAAGAACAAU    87.4％

1200   GAGAUCAUGAAGAUCUGUU    88.8％    1255    GUCACACAAAGAACAAUAG    87.4％

1201   ACCAAGAAAAUGGUCACAC    88 7％    1256    GGUCACACAAAGAACAAUA    87.4％

1202   CCAAGAAUAAUGGGUCACA    88.7％    1257    ACACCAUGGACACAGUCAA    87.4％

1203   UGACCAAGAAAAUGGUCAC    88.7％    1258    CCAGCGCAAAAUGCCAUAA    87.3％

1204   AUGACCAAGAAAAUGGUCA    88.7％    1259    GCAUGGUGGAGGCCAUGGU    87.3％

1205   CAUGAAGAUCUGUUCCACC    88 6％    1260    UUGAUGGACCACUACCUGA    87.3％

1206   AUGAAGAUCUGUUCCACCA    88.6％    1261    AGCAUGGUGGAGGCCAUGG    87.3％

1207   CAAGAAAAUGGUCACACAA    88 6％    1262    AAUGCACCAAAUCAUGAGG    87.2％

1208   UCAUGAGAAUCUGUUCCAC    88.5％    1263    AAUGUUCUCAAACAAAAUG    87.2％

1209   AUCAUGAAGAUCUGUUCCA    885％     1264    AUGCACCAAAUCAUGAGGG    87.2％

1210   GAUGGGCAUGUUCAACAUG    884％     1265    AUGGUGGAGGCCAUGGUGU    87.2％

1211   UGAUGGGCAUGUUCAACAU    88 4％    1266    GGUGGAGGCCAUGGUGUCU    87.2％

1212   AUGAGGGAAUACAAGCAGG    88.4％    1267    AUUGAUGGACCACUACCUG    87.2％

1213   ACAUGACCAAGAAAAUGGU    88.4％    1268    UGGUGGAGGCCAUGGUGUC    87.2％

1214   CAUGAGGGAAUACAAGCAG    88.4％    1269    AUAAUGUUCUCAAACAAAA    87.2％

1215   GAUGAUGGGCAUGUUCAAC    88.4％    1270    UAAUGUUCUCAAACAAAAU    87.2％

1216   AACAUGACCAAGAAAAUGG    88.4％    1271    GUGGAGGCCAUGGUGUCUA    87.1％

1217   AUGAUGGGCAUGUUCAACA    88.4％    1272    UGGCAAAUGUUGUGAGAAA    87.1％

1218   CAUGACAAGAAAAUUGGUC    88.3％    1273    GAAUGCACCAAAUCAUGAG    87.1％

1219   CUCAUAGUGAAUGCACCAA    88.3％    1274    AAUGGUCACACAAAGAACA    87.0％

1220   GACCAAGAAAAUGGUCACA    88.3％    1275    GAUCCUCCAUACAGCCAUG    86.9％

1221   UCAUAGUGAAUGCACCAAA    88.3％    1276    AUCCUCCAUACAGCCAUGG    86.9％

1222   AUGGGCAUGUUCAACAUGC    88.2％    1277    CAUGGUGGAGGCCAUGGUG    86.7％

1223   ACAACAUGACCAAGAAAAU    88.2％    1278    AAAUGGUCACACAAAGAAC    86.6％

1224   AUAGUGAAUGCACCAAAUC    88.2％    1279    GCAUGUUCAACAUGCUAAG    86.6％

1225   UAGUGAAUGCACCAAAUCA    88.2％    1280    AGGGAAUACAAGCAGGAGU    86.6％

1226   GCCAUGGUGUCUAGGGCCC    88.2％    1281    GGGCAUGUUCAACAUGCUA    86.6％

1227   GACAACAUGACCAAGAAAA    88.2％    1282    GGCAUGUUCAACAUGCUAA    86.6％

1228   UGGGCAUGUUCAACAUGCU    88.2％    1283    ACCAUGGACACAGUCAACA    86.6％

1229   CCAUGGUGUCUAGGGCCCG    88.2％    1284    GAUAUGCACAAACAGACUG    86.6％

1230   CAACAUGACCAAGAAAAUG    88.2％    1285    AAAAUGGUCACACAAAGAA    86.6％

1231   UGAAUGCACCAAAUCAUGA    88.1％    1286    CCAUGGACACAGUCAACAG    86.6％

1232   GUGAAUGCACCAAAUCAUG    88.0％    1287    GGAUAUGCACAAACAGACU    86.6％

1233   AGAUCAUGAAGAUCUGUUC    88.0％    1288    CACCAUGGACACAGUCAAC    86.5％

1234   UCAUGAGGGAAUACAAGCA    88.0％    1289    ACACAGUCAACAGAACACA    86.5％

1235   CAGCGCAAAAUGCCAUAAG    88.0％    1290    GACACAGUCAACAGAACAC    86.5％

1236   GAAUUCUUGAGGAUGAACA    88.0％    1291    GAGGGAAUACAAGCAGGAG    86.5％

1292    AUGUUCAACAUGCUAAGUA    86.4％    1351    AGAACAACAUGAUAAACAA    85.2％

1293    ACAUUCCCUUAUACUGGAG    864％     1352    GGGAAUUCUUGAGGAUGAA    85.2％

1294    UGUUCAACAUGCUAAGUAC    86.4％    1353    CAGGAGUGGAUAGAUUCUA    85.2％

1295    CAUUCCCUUAUACUGGAGA    86.4％    1354    AGUGGAUAUGCACAAACAG    85.2％

1296    AAGAAAAUGGUCACACAAA    86.3％    1355    AAGAACAACAUGAUAAACA    85.2％

1297    AAUACAAGCAGGAGUGGAU    86.3％    1356    AUAAAGAACAACAUGAUAA    85.2％

1298    AGAAAAUGGUCACACAAAG    863％     1357    UGGUGUCUAGGGCCCGGAU    85.0％

1299    GAAUACAAGCAGGAGUGGA    86.3％    1358    UGAUAAAGAACAACAUGAU    85.0％

1300    GGAAUACAAGCAGGAGUGG    86.3％    1359    AGCAGGAGUGGAUAGAUUC    85.0％

1301    UGAGGGAAUACAAGCAGGA    86.3％    1360    GUGAUAAAGAACAACAUGA    85.0％

1302    GGGAAUACAAGCAGGAGUG    86.3％    1361    GCAGGAGUGGAUAGAUUCU    85.0％

1303    GGACACAGUCAACAGAACA    86.2％    1362    GAUAAAGAACAACAUGAUA    85.0％

1304    AAGCAGGAGUGGAUAGAUU    86.2％    1363    AUGGUGUCUAGGGCCCGGA    85.0％

1305    UUGAGGAUGAACAGAUGUA    86.2％    1364    UGUCUAGGGCCCGGAUUGA    85.0％

1306    UGGACACAGUCAACAGAAC    86.2％    1365    CAUGGUGUCUAGGGCCCGG    84.9％

1307    AUGGACACAGUCAACAGAA    86.2％    1366    GAACAACAUGAUAAACAAU    84.9％

1308    AAAUCAUGAGGGAAUACAA    86.2％    1367    UGACUAAUUCACAAGACAC    84.8％

1309    CAAGCAGGAGUGGAUAGAU    86.2％    1368    GGAAGGCUAAUAGAUUUCC    84.8％

1310    CAAAUCAUGAGGGAAUACA    86.0％    1369    UUCCCUUAUACUGGAGAUC    84.8％

1311    CAUGGACACAGUCAACAGA    86.0％    1370    UCCCUUAUACUGGAGAUCC    84.8％

1312    CUUGAGGAUGAACAGAUGU    86.0％    1371    GAAGGCUAAUAGAUUUCCU    84.8％

1313    ACAAGCAGGAGUGGAUAGA    86.0％    1372    AUUGACUUCGAGUCUGGAC    84.8％

1314    CAUGUUCAACAUGCUAAGU    85.9％    1373    GGUGUCUAGGGCCCGGAUU    84.8％

1315    UAACAGUGAUAAAGAACAA    85.9％    1374    UAAUAGAUUUCCUCAAGGA    84.8％

1316    GAAAAUGGUCACACAAAGA    85.8％    1375    AACAGUGAUAAAGAACAAC    84.8％

1317    UGCACCAAAUCAUGAGGGA    85.7％    1376    GUGUCUAGGGCCCGGAUUG    84.8％

1318    GGCUAAUAGAUUUCCUCAA    85.7％    1377    ACUUCGAGUCUGGACGGAU    84.7％

1319    UCCUCCAUACAGCCAUGGA    85.6％    1378    ACAUGAUAAACAAUGACCU    84.7％

1320    CACCAAAUCAUGAGGGAAU    85.6％    1379    GUUCCAGCGCAAAAUGCCA    84.7％

1321    CCAAAUCAUGAGGGAAUAC    85.6％    1380    AUGACUAAUUCACAAGACA    84.7％

1322    ACCAAAUCAUGAGGGAAUA    85.6％    1381    AACAUGAUAAACAAUGACC    84.7％

1323    GCACCAAAUCAUGAGGGAA    85.6％    1382    CUAGGGCCCGGAUUGAUGC    84.7％

1324    GUAACAGUGAUAAAGAACA    85.6％    1383    GAUGACUAAUUCACAAGAC    84.7％

1325    UCUUGAGGAUGAACAGAUG    85.5％    1384    UCUAGGGCCCGGAUUGAUG    84.7％

1326    AAUUCUUGAGGAUGAACAG    85.5％    1385    AUUCCCUUAUACUGGAGAU    84.7％

1327    AGAUCCUCCAUACAGCCAU    85.5％    1386    UUGCAACUACACACUCCUG    84.6％

1328    UUCCAGCGCAAAAUGCCAU    85.5％    1387    UAAGAGACAACAUGACCAA    84.6％

1329    CUGGAGAUCCUCCAUACAG    85.5％    1388    UGCAACUACACACUCCUGG    84.6％

1330    ACAACAUGAUAAACAAUGA    85.5％    1389    CAACAUGAUAAACAAUGAC    84.6％

1331    GAGAUCCUCCAUACAGCCA    85.5％    1390    GUUGCAACUACACACUCCU    84.6％

1332    AACAACAUGAUAAACAAUG    85.5％    1391    CCAGCAACAGCCCAGAUGG    84.6％

1333    ACUGGAGAUCCUCCAUACA    85.5％    1392    CAGCAACAGCCCAGAUGGC    84.6％

1334    GGAGAUCCUCCAUACAGCC    85.5％    1393    GACUUCGAGUCUGGACGGA    84.5％

1335    UCCAGCGCAAAAUGCCAUA    85.5％    1394    AACUGGCAAAUGUUGUGAG    84.5％

1336    UUCUUGAGGAUGAACAGAU    85.5％    1395    GCAACUACACACUCCUGGA    84.5％

1337    AUUCUUGAGGAUGAACAGA    85.5％    1396    CUGGCAAAUGUUGUGAGAA    84.5％

1338    AGGGGAAUUCUUGAGGAUG    854％     1397    AAACUGGCAAAUGUUGUGA    84.5％

1339    UGGAGAUCCUCCAUACAGC    85.4％    1398    AAGUGGGAGCUAAUGGAUG    84.5％

1340    AUGAUGACUAAUUCACAAG    854％     1399    CUAAUAGAUUUCCUCAAGG    84.5％

1341    UGAUGACUAAUUCACAAGA    85.4％    1400    AGUGGGAGCUAAUGGAUGA    84.5％

1342    GUGGAUAUGCACAAACAGA    85.4％    1401    UAUGCACAAACAGACUGUG    84.3％

1343    UGGAUAUGCACAAACAGAC    85.3％    1402    CAACUACACACUCCUGGAU    84.3％

1344    AGUGAUAAAGAACAACAUG    85.3％    1403    ACUGGCAAAUGUUGUGAGA    84.3％

1345    ACAGUGAUAAAGAACAACA    85.3％    1404    AUGCACAAACAGACUGUGU    84.3％

1346    GGGGAAUUCUUGAGGAUGA    85.3％    1405    UGAAUGGAUGUCAAUCCGA    84.2％

1347    UAAAGAACAACAUGAUAAA    85.3％    1406    GAAUGGAUGUCAAUCCGAC    84.2％

1348    CAGUGAUAAAGAACAACAU    85.3％    1407    GAGUCUGGACGGAUUAAGA    84.2％

1349    UUUGACUUCGAUCUGGACG    85.3％    1408    UGACUUCGAGUCUGGACGG    84.2％

1350    AAAGAACAACAUGAUAAAC    85.2％    1409    GUCUAGGGCCCGGAUUGAU    84.1％

1410    AACUACACACUCCUGGAUU    84.1％    1469    GGCCCGGAUUGAUGCCAGA    83.4％

1411    UUGAAUGGAUGUCAAUCCG    84.1％    1470    AUACUGGAGAUCCUCCAUA    83.4％

1412    GAGACAACAUGACCAAGAA    84.1％    1471    UUACAUAUAUCACAAAAAA    83.3％

1413    AGGCUAAUAGAUUUCCUCA    84.1％    1472    CAACAGCCCAGAUGGCUCU    83.3％

1414    CGCAAAAUGCCAUAAGCAC    84.1％    1473    AGCCAUGGAACAGGAACAG    83.3％

1415    AGUCUGGACGGAUUAAGAA    84.1％    1474    GCCAUGGAACAGGAACAGG    83.3％

1416    AUAUGCACAAACAGACUGU    84.1％    1475    UUAUACUGGAGAUCCUCCA    83.3％

1417    UUUGAAUGGAUGUCAAUCC    84.0％    1476    CAAACUGGCAAAUGUUGUG    83.3％

1418    GCGCAAAAUGCCAUAAGCA    84.0％    1477    UACUGGAGAUCCUCCAUAC    83.3％

1419    CUACACACUCCUGGAUUCC    84.0％    1478    GAGUAACAGUGAUAAAGAA    83.3％

1420    UUCGAGUCUGGACGGAUUA    84.0％    1479    CUUAUACUGGAGAUCCUCC    83.3％

1421    UCGAGUCUGGACGGAUUAA    84.0％    1480    CCUUAUACUGGAGAUCCUC    83.3％

1422    AAGGCUAAUAGAUUUCCUC    84.0％    1481    GAAUUGACUUCGAGUCUGG    83.3％

1423    AGAGACAACAUGACCAAGA    84.0％    1482    AAGAAGUCCUAUAUAAAUA    83.3％

1424    CGAGUCUGGACGGAUUAAG    84.0％    1483    GCAACAGCCCAGAUGGCUC    83.3％

1425    ACUACACACUCCUGGAUUC    84.0％    1484    AUUUGAAUGGAUGUCAAUC    83.3％

1426    AGAGUAAGAGACAACAUGA    83.9％    1485    GCCAGAAUUGACUUCGAGU    83.2％

1427    AGCGCAAAAUGCCAUAAGC    83.9％    1486    CCAGAAUUGACUUCGAGUC    83.2％

1428    AGUAAGAGACAACAUGACC    83.9％    1487    CAAAGGGGAAUUCUUGAGG    83.2％

1429    GUAAGAGACAACAUGACCA    83.9％    1488    CAGAAUUGACUUCGAGUCU    83.2％

1430    UCAAUGGAUAAAGAGGAAA    83.9％    1489    AAAGGGGAAUUCUUGAGGA    83.2％

1431    AAGAGACAACAUGACCAAG    83.9％    1490    UCAGCUGAUAUGAGCAUUG    83.2％

1432    CAAUGGAUAAAGAGGAAAU    83.9％    1491    CCCGGAUUGAUGCCAGAAU    83.2％

1433    GAGUAAGAGAGCACAUGAC    83.9％    1492    GAGUGGAUAGAUUCUACAG    83.2％

1434    GCCAAAGGGGAAUUCUUGA    83.8％    1493    AGUAACAGUGAUAAAGAAC    83.2％

1435    AGACAACAUGACCAAGAAA    83.8％    1494    UACAUAUAUCACAAAAAAU    83.2％

1436    CUUCGAGUCUGGACGGAUU    83.8％    1495    CAGCUGAUAUGAGCAUUGG    83.2％

1437    AUGAUUACAUAUAUCACAA    83.8％    1496    GGAGUGGAUAGAUUCUACA    83.2％

1438    AGCCAAAGGGGAAUUCUUG    83.8％    1497    AGAAUUGACUUCGAGUCUG    83.2％

1439    GGACCAGCAACAGCCCAGA    83.7％    1498    CGAUGAUUACAUAUAUCAC    83.1％

1440    GACCAGCAACAGCCCAGAU    83.7％    1499    AAGGGGAAUUCUUGAGGAU    83.1％

1441    UGAUUACAUAUAUCACAAA    83.7％    1500    GAUUUCCUCAAGGAUGUGA    83.1％

1442    AUAGAUUUCCUCAAGGAUG    83.7％    1501    CUGAUAUGAGCAUUGGAGU    83.1％

1443    ACCAGCAACAGCCCAGAUG    83.7％    1502    GCUGAUAUGAGCAUUGGAG    83.1％

1444    ACAUAUAUCACAAAAAAUC    83.7％    1503    GCCCGGAUUGAUGCCAGAA    83.1％

1445    UAGAUUUCCUCAAGGAUGU    83.7％    1504    AAUAGAUUUCCUCAAGGAU    83.0％

1446    CAUAUAUCACAAAAAAUCA    83.7％    1505    AGGCCAAACUGGCAAAUGU    83.0％

1447    AUUACAUAUAUCACAAAAA    83.6％    1506    UGGAGUAACAGUGAUAAAG    83.0％

1448    GAUUACAUAUAUCACAAAA    83.6％    1507    UGAGCAUUGGAGUAACAGU    83.0％

1449    CCAAACUGGCAAAUGUUGU    83.6％    1508    CCGGAUUGAUGCCAGAAUU    83.0％

1450    AUUGAGAAAAUAAGGCCUC    83.6％    1509    AUGAGCAUUGGAGUAACAG    83.0％

1451    UUGAGAAAAUAAGGCCUCU    83.6％    1510    AUUUCCUCAAGGAUGUGAU    83.0％

1452    AUUGGAGUAACAGUGAUAA    83.6％    1511    GCGAUGAUUACAUAUAUCA    83.0％

1453    AGCUUGAACAGUCUGGACU    83.6％    1512    AAGGCCAAACUGGCAAAUG    83.0％

1454    GCCAAACUGGCAAAUGUUG    83.6％    1513    AGCUGAUAUGAGCAUUGGA    83.0％

1455    UUGGAGUAACAGUGAUAAA    83.6％    1514    CAUUGGAGUAACAGUGAUA    82.9％

1456    AAGCUUGAACAGUCUGGAC    83.6％    1515    AGAUUUCCUCAAGGAUGUG    82.9％

1457    GCUAAUAGAUU田CUCAAG    83.5％    1516    AGCAACAGCCCAGAUGGCU    82.9％

1458    AGGAGUGGAUAGAUUCUAC    83.5％    1517    GGCCAAACUGGCAAAUGUU    82.9％

1459    CAUGAUAAACAAUGACCUU    83.5％    1518    GCAUUGGAGUAACAGUGAU    82.9％

1460    ACCUUGGACCAGCAACAGC    83.4％    1519    AGCAUUGAGUAACUAGUGA    82.9％

1461    GACCUUGGACCAGCAACAG    83.4％    1520    CCCUUAUACUGGAGAUCCU    82.9％

1462    AAGAUUAUUGAGAAAAUAA    83.4％    1521    GGAUUGAUGCCAGAAUUGA    82.7％

1463    AGGGCCCGGAUUGAUGCCA    83.4％    1522    CGGAUUGAUGCCAGAAUUG    82.7％

1464    GGAGUAACAGUGAUAAAGA    83.4％    1523    AGAAGGCCAAACUGGCAAA    82.7％

1465    GGGCCCGGAUUGAUGCCAG    83.4％    1524    GAUGAUUACAUAUAUCACA    82.7％

1466    UUAGGGCCCGGAUUGAUCC    83.4％    1525    ACAGCCAUGGAACAGGAAC    82.7％

1467    UAUACUGGAGAUCCUCCAU    83.4％    1526    AAGAAGGCCAAACUGGCAA    82.7％

1468    AGAAAAUUGAGAAAAUAAG    83.4％    1527    GAAGGCCAAACUGGCAAAU    82.7％

1528    AUAUGAGCAUUCGAGUAAC    82.7％    1587    GAAAAUUGAGAAAAUAAGG    81.4％

1529    UAUGAGCAUUGGAGUAACA    82.7％    1588    CAAGCCAAAGGGGAAUUCU    81.4％

1530    UACAGCCAUGGAACAGGAA    82.7％    1589    ACAAACAGACUGUGUCCUG    81.46

1531    CUUGGACCAGCAACAGCCC    82.7％    1590    ACAAGCCAAAGGGGAAUUC    81.4％

1532    AUUGAUGCCAGAAUUGACU    82.7％    1591    CACAAACAGACUGUGUCCU    81.4％

1533    GAGCAUUGGAGUAACAGUG    82.7％    1592    AAGCCAAAGGGGAAUUCUU    81.3％

1534    UUGGACCAGCAACAGCCCA    82.7％    1593    CCAAUUGAUGGACCACUAC    81.3％

1535    AUGCCAGAAUUGACUUCGA    82.7％    1594    AACAAUGACCUUGGACCAG    81.3％

1536    UUGAUGCCAGAAUUGACUU    82.7％    1595    UGGAUUCCCAAGAGGAACC    81.3％

1537    GAUAUGAGCAUUGGAGUAA    82.7％    1596    GCACAAACAGACUGUGUCC    81.3％

1538    GAUGCCAGAAUUGACUUCG    82.7％    1597    ACAAUGACCUUGGACCAGC    81.3％

1539    AAUUGACUUCGAGUCUGGA    82.6％    1598    CAAUUGAUGGACCACUACC    81.3％

1540    UGAUAUGAGCAUUGGAGUA    82.6％    1599    AAACAAUGACCUUGGACCA    81.3％

1541    AUACAGCCAUGGAACAGGA    82.6％    1600    UCCUUGAAGAAUCCCACCC    81.3％

1542    CAGCCAUGGAACAGGAACA    82.6％    1601    UGCACAAACAGACUGUGUC    81.3％

1543    UGAUGCCAGAAUUGACUUC    82.5％    1602    UUCCUUGAAGAAUCCCACC    81.3％

1544    GAUUGAUGCCAGAAUUGAC    82.5％    1603    AAUAAGGCCUCUUCUAAUA    81.3％

1545    UGGACCAGCAACAGCCCAG    82.5％    1604    GGAUUCCCAAGAGGAACCG    81.3％

1546    GUGAAUCUUGGGCAAAAGA    82.4％    1605    UAUCACAAAAAAUCAACCU    81.2％

1547    UGAUGGACCACUACCUGAG    82.4％    1606    UUGAAGAAUCCCACCCAGG    812％

1548    UGCCAGAAUUGCUUUCGAG    82.4％    1607    CUUGAAGAAUCCCACCCAG    81.2％

1549    UGGCGAUGAUUACAUAUAU    82.4％    1608    CCUGGAUUCCCAAGAGGAA    81.2％

1550    GUGGGAGCUAAUGGAUGAG    82.3％    1609    ACCACAUUCCCUUAUACUG    81.2％

1551    GGCGAUGAUUACAUAUAUC    82.3％    1610    CCCAAUUGAUGGACCACUA    81.2％

1552    UAAAGUGGGAGCUAAUGGA    82.3％    1611    AAUUGAGAAAAUAAGGCCU    81.2％

1553    AAAGUGGGAGCUAAUGGAU    82.2％    1612    UCCUGGAUUCCCAAGAGGA    81.2％

1554    UUGAAUUCACAAGCUUUUU    82.0％    1613    CCACAUUCCCUUAUACUGG    81.2％

1555    UUUGAAUUCACAAGCUUUU    82.0％    1614    CCUUGAAGAAUCCCACCCA    81.0％

1556    AAAAUUGAGAAAAUAAGGC    81.8％    1615    AACACAAGCCAAAGGGGAA    81.0％

1557    CCUUGGACCAGCAACAGCC    81.8％    1616    AUGACCUUGGACCAGCAAC    81.0％

1558    UAAACAAUGACCUUGGACC    81.8％    1617    UAAGGCCUCUUCUAAUAGA    81.0％

1559    GAUGGACCACUACCUGAGG    81.8％    1618    AAUGACCUUGGACCAGCAA    81.0％

1560    AAAUUGAGAAAAUAAGGCC    81.8％    1619    ACACAAGCCAAAGGGGAAU    81.0％

1561    AUUUGAAUUCACAAGCUUU    81.7％    1620    GAUCAUUCGAGCUAAAGAA    81.0％

1562    CCAAAGGGGAAUUCUUGAG    81.7％    1621    UGACCUUGGACCAGCAACA    81.0％

1563    CAUUUGAAUUCACAAGCUU    81.7％    1622    CUCCUGGAUUCCCAAGAGG    80.9％

1564    AUGGACCACUACCUGAGGA    81.7％    1623    CUGGAUUCCCAAGAGGAAC    80.9％

1565    ACAUUUGAAUUCACAAGCU    81.7％    1624    CAAUGACCUUGGACCAGCA    80.9％

1566    ACACACUCCUGGAUUCCCA    81.6％    1625    CACAAGCCAAAGGGGAAUU    80.9％

1567    CACACUCCUGGAUUCCCAA    81.6％    1626    UCAUUCGAGCUAAAGAAGC    80.8％

1568    ACACUCCCUGGAUUCCAAG    81.5％    1627    AUAAGGCCUCUUCUAAUAG    80.8％

1569    GAUAAACAAUGACCUUGGA    81.5％    1628    CAUUCGAGCUAAAGAAGCU    80.8％

1570    AUAUCACAAAAAAUCAACC    81.5％    1629    AUCAUUCGAGCUAAAGAAG    80.8％

1571    CACUCCUGGAUUCCCAAGA    81.5％    1630    CAAAAUGCCAUAAGCACCA    80.7％

1572    GAGGAGACACACAAAUUCA    81.5％    1631    AAAUGCCAUAAGCACCACA    80.6％

1573    ACUCCUGGAUUCCCAAGAG    81.5％    1632    AAAAUGCCAUAAGCACCAC    80.6％

1574    AGAUCAUUCGAGCUAAAGA    81.5％    1633    GCAAAAUGCCAUAAGCACC    80.6％

1575    UACACACUCCUGGAUUCCC    81.5％    1634    AUGCCAUAAGCACCACAUU    80.6％

1576    AGAGGAGACACACAAAUUC    81.5％    1635    AAUGCCAUAAGCACCACAU    80.6％

1577    UAUAUCACAAAAAAUCAAC    81.5％    1636    UAAGCACCACAUUCCCUUA    80.4％

1578    AUCACAAAAAAUCAACCUG    81.5％    1637    AUAAGCACCACAUUCCCUU    80.4％

1579    AUAUAUCACAAAAAAUCAA    81.5％    1638    UUCAACAUGCUAAGUACGG    80.3％

1580    AUAAACAAUGACCUUGGAC    81.5％    1639    UUCCUCAAGGAUGUGAUGG    80.3％

1581    UGUUCGAGAAAUUUUUCCC    81.5％    1640    GUUCAACAUGCUAAGUACG    80.3％

1582    AACCCAAUUGAUGGACCAC    81.5％    1641    UUUCCUCAAGGAUGUGAUG    80.3％

1583    UCACAAAAAAUCAACCUGA    81.5％    1642    GAAUCAAUGGAUAAAGAGG    80.3％

1584    ACCCAAUUGAUGGACCACU    81.4％    1643    UCAACAUGCUAAGUACGGU    80.3％

1585    CAAACAGACUGUGUCCUGG    81.4％    1644    CCAAGAGGAACCGCUCUAU    80.3％

1586    AAACAGACACUGUCCUGGA    81.4％    1645    CUGAGAUCAUGAAGAUCUG    80.2％

1646   CCCAAGAGGAACCGCUCUA    80.2％    1705    UGAUGGAAUCAAUGGAUAA    79.1％

1647   UGCCAUAAGCACCACAUUC    80.2％    1706    CUGCUUAAAGUGGGAGCUA    79.0％

1648   UCCCAAGAGGAACCGCUCU    80.2％    1707    UGGAAUCAAUGGAUAAAGA    79.0％

1649   GCCAUAAGCACCACAUUCC    80.2％    1708    AAACAAGGGUGGACAAACU    78.9％

1650   UUCCCAAGAGGAACCGCUC    80.2％    1709    GGUUCAGAAACAUCCUGAG    78.9％

1651   AAUCAAUGGAUAAAGAGGA    80.2％    1710    CAACUCAACCCAAUUGAUG    78.9％

1652   UUAAAGUGGGAGCUAAUGG    80.2％    1711    UGGUUCAGAAACAUCCUGA    78.9％

1653   CCAUAAGCACCACAUUCCC    80..2％   1712    AACUCAACCCAAUUGAUGG    78.9％

1654   CAUAAGCACCACAUUCCCU    80.2％    1713    AUUCGAGCUAAAGAAGCUG    78.8％

1655   AUUCCCAAGAGGAACCGCU    80.1％    1714    CAAACAAGGGUGGACAAAC    78.8％

1656   GAUUCCCAAGAGGAACCGC    80.1％    1715    AUCAAUGGAUAAAGAGGAA    78.8％

1657   UCCUCAAGGAUGUGAUGGA    80.0％    1716    AUGGAAUCAAUGGAUAAAG    78.8％

1658   UGAGAAAAUAAGGCCUCUU    80.0％    1717    GUUCAGAAACAUCCUGAGC    78.7％

1659   AAGAGGAACCGCUCUAUUC    80.0％    1718    CAACAUGCUAAGUACGGUU    78.7％

1660   GAGACACACAAAUUCAGAC    80.0％    1719    UUCAGAAACAUCCUGAGCA    78.6％

1661   CAAGAGGAACCGCUCUAUU    80.0％    1720    GGAAUCAAUGGAUAAAGAG    78.6％

1662   GGAGACACAC出AUUCAGA    80 0％    1721    UCAGAAACAUCCUGAGCAU    78.6％

1663   UGAGAUCAUGAAGAUCUGU    80.0％    1722    CAACUGCAUUAGCCAACAC    78.5％

1664   GAGCUAAAGAAGCUGUGGG    80.0％    1723    GCAACUGCAUUAGCCAACA    78.5％

1665   AGAGGAACCGCUCUAUUCU    80.0％    1724    AAGUGGAUAUGCACAAACA    78.5％

1666   AGCUAAAGAAGCUGUGGGA    79.9％    1725    CAAGUGGAUAUGCACAAAC    78.5％

1667   AGAAAAUAAGGCCUCUUCU    79.9％    1726    CCAAGUGGAUAUGCACAAA    78.5％

1668   AAAAUAAGGCCUCUUCUAA    79.9％    1727    AGAAACAUCCUGAGCAUCG    78.3％

1669   CACAUUCCCUUAUACUGGA    79.9％    1728    ACAUGCUAAGUACGGUUUU    78.3％

1670   GAAGUCUGCUUAAAGUGGG    79.8％    1729    GAAACAUCCUGAGCAUCGC    78.3％

1671   AAAUAAGGCCUCUUCUAAU    79.8％    1730    AACAUGCUAAGUACGGUUU    78.3％

1672   GAGAAAAUAAGGCCUCUUC    79.8％    1731    ACACACAAAUUCAGACGAG    78.2％

1673   AGUCUGCUUAAAGUGGGAG    79.7％    1732    GCAUCACAUUCCCUUAUAC    78.2％

1674   CCACUACCUGAGGAUAAUG    79.7％    1733    GCUAAUUUUAGCAUGGAGC    78.2％

1675   AAGUCUGCUUAAGUGGGGA    79 7％    1734    ACAUCCUGAGCAUCGCACC    78.2％

1676   AUGUGAUGGAAUCAAUGGA    79.6％    1735    AAUUGAUGGACCACUACCU    78.2％

1677   GAUGUGAUGGAAUCAAUGG    79.6％    1736    CAGAAACAUCCUGAGCAUC    78.2％

1678   GAAAAUAAGGCUCUUUCUA    79.6％    1737    AGCACCACAUUCCCUUAUA    78.2％

1679   CACUACCUGAGGAUAAUGA    79.6％    1738    GACACACAAAUUCAGACGA    78.2％

1680   UUCGAGCUAAAGAAGCUGU    79.4％    1739    AACAUCCUGAGCAUCGCAC    78.2％

1681   GGACCACUACCUGAGGAUA    79.4％    1740    AAGCACCACAUUCCCUUAU    78.2％

1682   UCGAGCUAAAGAAGCUGUG    79.4％    1741    CUAAUUUUAGCAUGGAGCU    78.2％

1683   ACCACUACCUGAGGAUAAU    79.4％    1742    AAACAUCCUGAGCAUCGCA    78.1％

1684   GACCACUACCUGAGGAUAA    79.4％    1743    CACCACAUUCCCUUAUACU    78.0％

1685   CGAGCUAAAGAAGCUGUGG    79.4％    1744    GAUGGAAUCAAUGGAUAAA    78.0％

1686   UCUGCUUAAAGUGGGAGCU    79.4％    1745    AGACACACAAAUUCAGACG    78.0％

1687   UGGACCACUACCUGAGGAU    79.4％    1746    AAGGAUGUGAUGGAAUCAA    77.7％

1688   GUCUGCUUAAAGUGGGAGC    79.4％    1747    AGGAUGUGAUGGAAUCAAU    77.7％

1689   GAAGCUCCGAACACAAAUA    79.3％    1748    UGGGAUGGGCUCCAAUCCU    77.6％

1690   AUGAAGCUCCGAACACAAA    79.3％    1749    AUGCCGUUGCAACUACACA    77.6％

1691   CCAGUUUUGGAGUGUCUGG    79.3％    1750    UGAUGCCGUUGCAACUACA    77.6％

1692   CCCAGUUUUGGAGUGUCUG    79.3％    1751    GUGGGAUGGGCUCCAAUCC    77.6％

1693   UGAAGCUCCGAACACAAAU    79.3％    1752    GAUGCCGUUGCAACUACAC    77.6％

1694   CAGAAAUGCUAGCAAGCAU    79.2％    1753    AUGAUGCCGUUGCAACUAC    77.6％

1695   GUGAUGGAAUCAAUGGAUA    79.2％    1754    UAUGAUGCCGUUGCAACUA    77.6％

1696   GCAGAAAUGCUAGCAAGCA    79.2％    1755    GGGAUGGGCUCCAAUCCUC    77.6％

1697   UGUGAUGGAAUCAAUGGAU    79.2％    1756    AAUGGAUGUCAAUCCGACU    77.5％

1698   UGCUUAAAGUGGGAGCUAA    79.2％    1757    GGAUGUGAUGGAAUCAAUG    77.5％

1699   GGUGGGAUGGGCUCCAAUC    79.2％    1758    GAUUUGUGGCUAAUUUUAG    77.5％

1700   AAGCUCCGAACACAAAUAC    79.2％    1759    GGAUUUGUGGCUAAUUUUA    77.5％

1701   UGGUGGGAUGGGCUCCAAU    79.2％    1760    GGCACAGCAUCAUUGAGCC    77.3％

1702   GCUUAAAGUGGGAGCUAAU    79.2％    1761    GUGGCUAAUUUUAGCAUGG    77.3％

1703   AGCUCCGAACACAAAUACC    79.2％    1762    UUUGUGGCUAAUUUUAGCA    77.3％

1704   CUUAAAGUGGGAGCUAAUG    79.2％    1763    GCACAGCAUCAUUGAGCCC    77.3％

1764    UGGCUAAUUUUAGCAUGGA    77.3％    1823    CUUGAACAGUCUGGACUUC    76.4％

1765    GGCUAAUUUUAGCAUGGAG    77.3％    1824    CCACCAUUGAAGAACUCAG    76.4％

1766    UGGAUUUGUGGCUAAUUUU    77.3％    1825    AGUGGAUAGAUUCUACAGG    76.4％

1767    UAUGGAUUUGUGGCUAAUU    77.3％    1826    AGCUUUCUUUCACAAUCAC    76.4％

1768    UGUGGCUAAUUUUAGCAUG    77.3％    1827    UUGAACAGUCUGGACUUCC    76.4％

1769    AUGGAUUUGUGGCUAAUUU    77.3％    1828    UUGCAACACCCGGGAUGCA    76.3％

1770    UUGUGGCUAAUUUUAGCAU    77.3％    1829    UUCAACAAACAAGGGUGGA    76.3％

1771    CAAGGAUGUGAUGGAAUCA    77.2％    1830    AUUGCAACACCCGGGAUGC    76.3％

1772    ACUACCUGAGGAUAAUGAG    77.2％    1831    AUGUCAAUCCGACUCUACU    76.3％

1773    CUCAAGGAUGUGAUGGAAU    77.2％    1832    UGCCCUCAUAGUGAAUGCA    76.1％

1774    GCCCUCAUAGUGAAUGCAC    77.2％    1833    UGGAUGUCAAUCCGACUCU    76.1％

1775    CUACCUGAGGAUAAUGAGC    77.2％    1834    UUGCCCUCAUAGUGAAUGC    76.1％

1776    UCAAGGAUGUGGAUGAAUC    77.2％    1835    GCAACACCCGGGAUGCAAA    76.1％

1777    AUAUGAUGCCGUUGCAACU    77.1％    1836    CAACACCCGGGAUGCAAAU    76.1％

1778    GAAUAUGAUGCCGUUGCAA    77.1％    1837    UGCAACACCCGGGAUGCAA    76.1％

1779    UACCUGAGGAUAAUGAGCC    77.1％    1838    UUUGCCCUCAUAGUGAAUG    76.0％

1780    AAUAUGAUGCCGUUGCAAC    77.1％    1839    AUGGAUGUCAAUCCGACUC    76.0％

1781    CCCUCAUAGUGAAUGCACC    77.1％    1840    ACAGAACACACCAAUAUUC    76.0％

1782    AUUUGUGGCUAAUUUUAGC    77.1％    1841    CAGAACACACCAAUAUUCA    76.0％

1783    UGGAAUAUGAUGCCGUUGC    77.0％    1842    AACAGAACACACCAAUAUU    76.0％

1784    AGAACACACCAAUAUUCAG    77.0％    1843    AGGAUGAACAGAUGUACCA    75.9％

1785    GGAAUAUGAUGCCGUUGCA    77.0％    1844    AUUUUGCCCUCAUAGUGAA    75.9％

1786    CAACAAACAAGGGUGGACA    77.0％    1845    UGAAGAACUCAGACGGCAA    75.9％

1787    CCUCAUAGUGAAUGCACCA    77.0％    1846    GCUUGAACAGUCUGGACUU    75.9％

1788    CAGCAUCAUUGAGCCCUGG    77.0％    1847    GAAGAACUCAGACGGCAAA    75.9％

1789    ACAGCAUCAUUGAGCCCUG    76.9％    1848    UGAGGAUGAACAGAUGUAC    75.9％

1790    CACAGCAUCAUUGAGCCCU    76.9％    1849    UUUUGCCCUCAUAGUGAAU    75.9％

1791    AUGGAAAUAUAUGCCGUUG    76.9％    1850    GAUGUCAAUCCGACUCUAC    75.9％

1792    AGAAGUCCUAUAUAAAUAA    76.8％    1851    GAUUUUGCCCUCAUAGUGA    75.9％

1793    CUGUUCCACCAUUGAAGAA    76.8％    1852    GGAUGUCAAUCCGACUCUA    75.9％

1794    AAGUACGGUUUUAGGAGUC    76.8％    1853    GAGGAUGAACAGAUGUACC    75.9％

1795    GAACACACCAAUAUUCAGA    76.8％    1854    UGAGCAAAAAGAAGUCCUA    75.8％

1796    CUCAGACGGCAAAAAUAAU    76.8％    1855    AUGAGCAAAAAGAAGUCCU    75.8％

1797    AGUACGGUUUUAGGAGUCU    76.8％    1856    AAGAACUCAGACGGCAAAA    75.8％

1798    UGCUAAGUACGGUUUUAGG    76.8％    1857    GUUCAACAAACAAGGGUGG    75.7％

1799    GUACGGUUUUAGGAGUCUC    76.8％    1858    UCAACAGAACACACCAAUA    75.7％

1800    CAUGCUAAGUACGGUUUUA    76.8％    1859    GUCAACAGAACACACCAAU    75.7％

1801    UAAGUCGGUUUUUAGGAGU    76.8％    1860    CAACAGAACACACCAAUAU    75.7％

1802    UCCACCAUUGAAGAACUCA    76.8％    1861    GCUAUUGCAACACCCGGGA    75.6％

1803    AGGAGACACACAAAUUCAG    76.8％    1862    UUCACAAGCUUUUUUUAUC    75.6％

1804    AUGCUAAGUACGGUUUUAG    76.8％    1863    CUAUUGCAACACCCGGGAU    75.6％

1805    AGGUUCCAGCGCAAAAUGC    76.7％    1864    AAUUCACAAGCUUUUUUUA    75.6％

1806    AAGGUUCCAGCGCAAAAUG    76.7％    1865    UGAAUUCACAAGCUUUUUU    75.6％

1807    AAAGGUUCCAGCGCAAAAU    76.7％    1866    GAAUUCACAAGCUUUUUUU    75.6％

1808    UAAAGGUUCCAGCGCAAAA    76.7％    1867    UAUUGCAACACCCGGGAUG    75.6％

1809    UGUUCCACCAUUGAAGAAC    76.6％    1868    UCACAAGCUUUUUUUAUCG    75.6％

1810    GUUCCACCAUUGAAGAACU    76.6％    1869    GUUCUCAAACAAAAUGGCA    75.5％

1811    CAUUGAAGAACUCAGACGG    76.6％    1870    UUCUCAAACAAAAUGGCAA    75.5％

1812    CUAAGUACGGUUUUAGGAG    76.6％    1871    AGAAGGGCUAUUGCAACAC    75.5％

1813    CCAUUGAAGAACUCAGACG    76.6％    1872    GAAGUUUUUAGAUCGAAUG    75.5％

1814    ACCAUUGAAGAACUCAGAC    76.6％    1873    UGCCUUGAAACAAUGGAAG    75.5％

1815    GCUAAGUACGGUUUUAGGA    76.6％    1874    AGAACUCAGACGGCAAAAA    75.5％

1816    UUCCACCAUUGAAGAACUC    76.6％    1875    AUUCACAAGCUUUUUUUAU    75.5％

1817    CACCAUUGAAGAACUCAGA    76.6％    1876    GAAGGGCUAUUGCAACACC    75.5％

1818    AUUGAAGAACUCAGACGGC    76.5％    1877    UCUCAAACAAAAUGGCAAG    75.4％

1819    GUGGAUAGAUUCUACAGGA    76.5％    1878    UACAUGUUCGAGAGUAAGA    75.3％

1820    GGUUCCAGCGCAAAAUGCC    76.5％    1879    UCUGAGAUCAUGAAGAUCU    75.3％

1821    UUGAAGAACUCAGACGGCA    76.5％    1880    AAGAAGGGCUAUUGCAACA    75.3％

1822    GAGCUUUCUUUCACAAUCA    76.4％    1881    ACAUGUUCGAGAGUAAGAG    75.3％

1882   GAAAAGGAUACAUGUUCGA    75.3％    1941    CAACACACUUUCAAAGAAA    74.4％

1883   GGAAAAGGAUACAUGUUCG    75.3％    1942    CCAUAGAAGUUUUUAGAUC    74.4％

1884   AAAGAAGGGCUAUUGCAAC    75.2％    1943    GCCAGCCCAUGGUCCAGCC    74.3％

1885   AAAAGAAGGGCUAUUGCAA    75.2％    1944    AAACUGGGGCACCCCAACU    74.3％

1886   GAACUCAGACGGCAAAAAU    75.2％    1945    CAGAAACUGGGGCACCCCA    74.3％

1887   UCAACAAACAAGGGUGGAC    75.1％    1946    AGAAACUGGGGCACCCCAA    74.3％

1888   CCUGAGUGGUUCAGAAACA    75.1％    1947    ACAGAAACUGGGGCACCCC    74.3％

1889   CAAACAAAAUGGCAAGACU    75.1％    1948    AAAGAAGUCCUAUAUAAAU    74.3％

1890   CUGAGUGGUUCAGAAACAU    75.1％    1949    CGAUGACCAAAGAUGCAGA    74.3％

1891   UCAAACAAAAUGGCAAGAC    75.0％    1950    ACGAUGACCAAAGAUGCAG    74.3％

1892   AGAAGUUUUUAGAUCGAAU    75.0％    1951    GAAACUGGGGCACCCCAAC    74.3％

1893   AACUCAACGGCAAAAAAUA    75.0％    1952    CCAGCCCAUGGUCCAGCCA    74.3％

1894   AUAGAAGUUUUUAGAUCGA    75.0％    1953    GAGAAGAUCAUUCGAGCUA    74.3％

1895   GGAUACAUGUUCGAGAGUA    75.0％    1954    AGGAUACAUGUUCGAGAGU    74.2％

1896   UAGAAGUUUUUAGAUCGAA    75.0％    1955    GCCUUGAAACAAUGGAAGU    74.2％

1897   CUCAAACAAAAUGGCAAGA    75.0％    1956    AAGGAUACAUGUUCGAGAG    74.2％

1898   AGAAGAUCAUUCGAGCUAA    75.0％    1957    AUAAUGAGCCAAGUGGAUA    74.2％

1899   AUACAUGUUCGAGAGUAAG    74.9％    1958    AAAGGAUACAUGUUCGAGA    74.2％

1900   AUCAACAUGAGCAAAAAGA    74.9％    1959    GUAAGAGAAUGAAGCUCCG    74.1％

1901   UCAACAUGAGCAAAAAGAA    74.9％    1960    ACAUGAGCAAAAAGAAGUC    74.1％

1902   AGUGGUUCAGAAACAUCCU    74.9％    1961    CCGUUGCAACUACACACUC    74.1％

1903   GAUACAUGUUCGAGAGUAA    74.9％    1962    GAGCCAAGUGGAUAUGCAC    74.1％

1904   GGAAUCAACAUGAGCAAAA    74.9％    1963    AAGUUUUUAGAUCGAAUGG    74.1％

1905   GAGUGGUUCAGAAACAUCC    74.9％    1964    CUGGGGCACCCCAACUCAA    74.1％

1906   GUGGUUCAGAAACAUCCUG    74.9％    1965    AACUGGGGCACCCCAACUC    74.1％

1907   AAAAGAAGUCCUAUAUAAA    74.8％    1966    AUGAGCCAAGUGGAUAUGC    74.1％

1908   UGAGUGGUUCAGAAACAUC    74.8％    1967    AACAUGAGCAAAAAGAAGU    74.1％

1909   GAAUCAACAUGAGCAAAAA    74.8％    1968    CAGUCAACAGAACACACCA    74.1％

1910   CCUCAAGGAUGUGAUGGAA    74.8％    1969    UUUCAAAGAAAAAGGAGAG    74.1％

1911   AAAAAGAAGUCCUAUAUAA    74.8％    1970    UGAGCCAAGUGGAUAUGCA    74.1％

1912   UAACAACACAGUUUCAAAG    74.7％    1971    UGGGAUCAAACCCAAUCAA    74.1％

1913   AAUCAACAUGAGCAAAAAG    74.7％    1972    ACUGGGGCACCCCAACUCA    74.1％

1914   UUUCUUUCACAAUCACUGG    74.7％    1973    GCCGUUGCAACUACACACU    74.1％

1915   AUAACAACACACUUUCAAA    74.5％    1974    AGCCAAGUGGAUAUGCACA    74.1％

1916   UGACAUUGAACACGAUGAC    74.5％    1975    GCCAACGUGGAUAUGCCAA    74.1％

1917   GAAGAUCAUUCGAGCUAAA    74.5％    1976    AGUAAGAGAAUGAAGCUCC    74.1％

1918   ACUCAACCCAAUUGAUGGA    74.5％    1977    UUCAAAGAAAAAGGAGAGU    74.1％

1919   CACCAUAGAAGUUUUUAGA    74.5％    1978    ACAGUCAACAGAACACACC    74.1％

1920   CUCAACCCAAUUGAUGGAC    74.5％    1979    GCUUUCUUUCACAAUCACU    74.0％

1921   UCAACCCAAUUGAUGGACC    74.5％    1980    UGGGAAUCAACAUGAGCAA    74.0％

1922   CAACCCAAUUGAUGGACCA    74.5％    1981    UCAAAGAAAAAGGAGAGUA    74.0％

1923   UUGACAUUGAACACGAUGA    74.5％    1982    AAUGAGCCAAGUGGAUAUG    74.0％

1924   ACACACUUUCAAAGAAAAA    745％     1983    GGGGCACCCCAACUCAACC    74.0％

1925   UUCUCUGAGAUCAUGAAGA    74.5％    1984    ACAGACUGUGUCCUGGAGG    74.0％

1926   ACACCAUAGAAGUUUUUAG    74.5％    1985    CAACAUGAGCAAAAAGAAG    74.0％

1927   CACACUUUCAAAGAAAAAG    74.5％    1986    UCAAAGACUACAGAUAUAC    74.0％

1928   AACACCAUAGAAGUUUUUA    74.5％    1987    GGGCACCCCAACUCAACCC    74.0％

1929   ACCAUCGAAGUUUUUAGAU    74.5％    1988    UAAUGAGCCAAGUGGAUAU    74.0％

1930   ACAACACACUUUCAAAGAA    74.4％    1989    CUUUCUUUCACAAUCACUG    74.0％

1931   CUCUGAGAUCAUGAAGAUC    74.4％    1990    UGGGGCACCCCAACUCAC     74.0％

1932   AACAACACACUUUCAAAGA    74.4％    1991    GUGGGAAUCAACAUGAGCA    74.0％

1933   GAUAACAACACACUUUCAA    74.4％    1992    CAGACUGUGUCCUGGAGGC    74.0％

1934   GAGAUAACAACACACUUUC    74.4％    1993    CGUUGCAACUACACACUCC    73.9％

1935   AACACACUUUCAAAGAAAA    74.4％    1994    CACAGUCAACAGAACACAC    73.9％

1936   UCUCUGAGAUCAUGAAGAU    74.4％    1995    ACACGAUGCCAAAGAUUGC    73.9％

1937   UGCCAGCCCAUGGUCCAGC    74.4％    1996    AGUCAACAGAACACACCAA    73.9％

1938   ACGAGAAGAUCAUUCGAGC    74.4％    1997    AACACGAUGACCAAAGAUG    73.9％

1939   CGAGAAGAUCAUUCGAGCU    74.4％    1998    AUGCCAGCCCAUGGUCCAG    73.9％

1940   AGAUAACAACACACUUUCA    74.4％    1999    AAAGAAAAAGGAGAGUAAG    73.9％

2000    CAAAGAAAAAGGAGAGUAA    73.9％    2059    ACCUGAGUGGUUCAGAAAC    72.9％

2001    AACAGACUGUGUCCUGGAG    73.9％    2060    CAAAAGAAAUACACCAAGA    72.9％

2002    UAAAAAGAAGGGCUAUUGC    73.8％    2061    UUUCUAGCAUGGUGGAGGC    72.9％

2003    CACGAUGACCAAAGAUGCA    73.8％    2062    AGGAAAAGGAUACAUGUUC    72.8％

2004    UGCCGUUGCAACUACACAC    73.8％    2063    AAAAGCUUGAACAGUCUGG    72.8％

2005    AAAUUAAAAAGAAGGGCUA    73.8％    2064    GGAAUUUCUAGCAUGGUGG    72.8％

2006    AAUUAAAAAGAAGGGCUAU    73.8％    2065    ACAAAAAAUCAACCUGAGU    72.8％

2007    AAAAAGAAGGGCUAUUGCA    73.8％    2066    AAAAAAUCAACCUGAGUGG    72.8％

2008    UUAAAAAGAAGGGCUAUUG    73.8％    2067    AAGAAAUACACCAAGACAA    72.8％

2009    AUUAAAAAGAAGGGCUAUU    73.7％    2068    AACAAAAUGGCAAGACUAG    72.8％

2010    GAACACGAUGACCAAAGAU    73.7％    2069    CAAAAAAUCAACCUGAGUG    72.8％

2011    UGAACACGAUGACCAAAGA    73.7％    2070    AGAAAUACACCAAGACAAC    72.8％

2012    GACAUUGAACACGAUGACC    73.6％    2071    AAGAAAAAACAAAGAGUGA    72.8％

2013    GAUAAUGAGCCAAGUGGAU    73.6％    2072    AAAGCUUGAACAGUCUGGA    72.8％

2014    CAUUGAACACGAUGACCAA    73.6％    2073    UGGAAUUUCUAGCAUGGUG    72.8％

2015    ACAUUGAACACGAUGACCA    73.6％    2074    AAUUUCUAGCAUGGUGGAG    72.8％

2016    UUUGAGAACUCAUGCCUUG    73.6％    2075    GAAAAGCUUGAACAGUCUG    72.8％

2017    UUGAGAACUCAUGCCUUGA    73.6％    2076    GAAUUUCUAGCAUAGUGGA    72.8％

2018    CAUAGAAGUUUUUAGAUCG    73.6％    2077    UUCUAGCAUGGUGGAGGCC    72.8％

2019    CAGCCCAUGGUCCAGCCAA    73.6％    2078    AAAGACUACAGAAUUACAU    72.7％

2020    AGAAUGAAGCUCCGAACAC    73.5％    2079    GGGCAAAAGAAAUACACCA    72.7％

2021    AAUGAAGCUCCGAACACAA    73.5％    2080    AAUACACCAAGACAACAUA    72.7％

2022    GAAUGAAGCUCCGAACACA    73.5％    2081    AAAGAAAUACACCAAGACA    72.7％

2023    UAGCCAACACCAUAGAAGU    73.4％    2082    UCCUAAAGGUUCCAGCGCA    72.7％

2024    AACCUGAGUGGUUCAGAAA    73.4％    2083    UAAGAGAAUGAAGCUCCGA    72.7％

2025    GCCAACACCAUAGAAGUUU    73.4％    2084    AAGAGAAUGAAGCUCCGAA    72.7％

2026    CCAACACCAUAGAAGUUUU    73.4％    2085    UUUGCGAAAAGCUUGAACA    72.7％

2027    UGAAUCUUGGGCAAAAGAA    73.4％    2086    CCUAAAGGUUCCAGCGCAA    72.7％

2028    CAACCUGAGUGGUUCAGAA    73.4％    2087    AUUUGCGAAAAGCUUGAAC    72.7％

2029    CAACACCAUAGAAGUUUUU    73.4％    2088    AGAGAAUGAAGCUCCGAAC    72.7％

2030    UAGGAAAAGGAUACAUGUU    73.3％    2089    UUCCUAAAGGUUCCAGCGC    72.7％

2031    GAGAACUCAUGCCUUGAAA    73.3％    2090    AAGACUACAGAUAUACAUA    72.7％

2032    UCAACCUGAGUGGUUCAGA    73.3％    2091    CACAAAAAAUCAACCUGAG    72.7％

2033    AGCAAAAAGAAGUCCUAUA    73 3％    2092    AAAUACACCAAGACAACAU    72.7％

2034    AGCCAACACCAUAGAAGUU    73.3％    2093    CAUUUGCGAAAAGCUUGAA    72.7％

2035    GAGCAAAAAGAAGUCCUAU    73 3％    2094    CAAAGACUACAGAUAUACA    72.6％

2036    GCAAAAAGAAGUCCUAUAU    73.3％    2095    CCAAUAAUGUUCUCAAACA    72.6％

2037    AGAACUCAUGCCUUGAAAC    73.3％    2096    GAGAAUGAAGCUCCGAACA    72.6％

2038    UCAUCAAAGACUACAGAUA    73.2％    2097    GAAAUACACCAAGACAACA    72.6％

2039    UGAGAACUCAUGCCUUGAA    73.2％    2098    AACAAACAAGGGUGGACAA    72.6％

2040    UUGGAAUUUCUAGCAUGGU    73.2％    2099    AAACAAAAUGGCAAGACUA    72.6％

2041    UUCAUCAAAGACUACAGAU    73.2％    2100    UCUUUGAGAACUCAUGCCU    72.6％

2042    UUAGCCAACACCAUAGAAG    73.2％    2101    UCCUAUAUAAAUAAAACAG    72.6％

2043    ACUCAGACGGCAAAAAUAA    73.1％    2102    CCUAUAUAAAUAAAACAGG    72.6％

2044    UUGAACACGAUGACCAAAG    73.1％    2103    CAAUAAUGUUCUCAAACAA    72.6％

2045    AAAAGAAAUACACCAAGAC    73.1％    2104    UUCGAGAGUAAGAGAAUGA    72.6％

2046    CUAAAGGUUCCAGCGCAAA    73.1％    2105    GUUCGAGAGUAAGAGAAUG    72.6％

2047    AAUCAACCUGAGUGGUUCA    73.1％    2106    UGGGCAAAAGAAAUACACC    72.6％

2048    AUCAACCUGAGUGGUUCAG    73.1％    2107    CUUGGGCAAAAGAAAUACA    72.6％

2049    ACAAAAUGGCAAGACUAGG    73.1％    2108    UCGAGAGUAAGAGAAUGAA    72.6％

2050    AAAAAUCAACCUGAGUGGU    73.1％    2109    AUGUUCGAGAGUAAGAGAA    72.6％

2051    CAAAAAGAAGUCCUAUAUA    73.1％    2110    AAUAAUGUUCUCAAACAAA    72.6％

2052    UCUAGCAUGGUGGAGGCCA    72.9％    2111    UUGGGCAAAAGAAAUACAC    72.6％

2053    AAAAUCAACCUGAGUGGUU    72.9％    2112    UGUUCGAGAGUAAGAGAAU    72.6％

2054    AUUUCUAGCAUGGUGGAGG    72.9％    2113    ACAAACAAGGGUGGACAAA    72.5％

2055    UAGCAUGGUGGAGGCCAUG    72.9％    2114    ACUCAUGCCUUGAAACAAU    72.5％

2056    AAAUCAACCUGAGUGGUUC    72.9％    2115    GAAAAAGGAGAGUAAGAGA    72.5％

2057    AUUGAACACGAUGACCAAA    72.9％    2116    AAAAGGAGGAUAAGAGACA    72.5％

2058    CUAGCAUGGUGGAGGCCAU    72.9％    2117    GAAUCUUGGGCAAAAGAAA    72.5％

2118    CUAGGAAAAGGAUACAUGU    72.5％    2177    CUGUGUCCUGGAGGCUAUG    72.0％

2119    AGCAUUUGCGAAAAGCUUG    72.5％    2178    AACACUAAGUGGAAUGAAA    72.0％

2120    AUCUUUGAGAACUCAUGCC    72.5％    2179    AGGAGAGUAAGAGACAACA    72.0％

2121    AAAGGAGAGUAAGAGACAA    72.5％    2180    UGCAACUUGUUCGAGAAAU    72.0％

2122    GCAUUUGCGAAAAGCUUGA    72.5％    2181    ACACUAAGUGGAAUGAAAA    72.0％

2123    AUCUUGGGCAAAAGAAAUA    72.4％    2182    UGCUGCAACUUGUUCGAGA    72.0％

2124    GCGAAAAGCUUGAACAGUC    72.4％    2183    GCUGUGGGAUCAAACCCAA    72.0％

2125    UGUUCAUCAAAGACUACAG    72.4％    2184    CCAACUCAACCCAAUUGAU    72.0％

2126    AAUCUUGGGCAAAAGAAAU    72.4％    2185    GACUGUGUCCUGGAGGCUA    72.0％

2127    AGUUUUGGAGUGUCUGGAA    72.4％    2186    ACUUGUUCGAGAAAUUUUU    72.0％

2128    GAGCUUUGACAUUGAACAC    72.4％    2187    AAGGAGAGUAAGAGACAAC    72.0％

2129    AGAAAAAGGAGAGUAAGAG    72.4％    2188    AGACUAGGAAAAGGAUACA    72.0％

2130    CAAUUGUUCAUCAAAGACU    72.4％    2189    GCAACUUGUUCGAGAAAUU    72.0％

2131    AAUUGUUCAUCAAAGACUA    72.4％    2190    GGAGAGUAAGAGACAACAU    72.0％

2132    UCUUGGGCAAAAGAAAUAC    72.4％    2191    GUCCUAUAUAAAUAAAACA    71.9％

2133    AACUCAUGCCUUGAAACAA    72.4％    2192    CUAAUAAGAGCUUUGACAU    71.9％

2134    AGAAAAAACAAAGAGUGAA    72.4％    2193    CAACUUGUUCGAGAAAUUU    71.9％

2135    UGCGAAAAGCUUGAACAGU    72.4％    2194    AAAAUGGCAAGACUAGGAA    71.9％

2136    AGACUACAGAUAUACAUAU    72.4％    2195    CUGGACGGAUUAAGAAGGA    71.9％

2137    UUGCGAAAAGCUUGAACAG    72.4％    2196    GAAGUCCUAUAUAAAUAAA    71.9％

2138    CGAAAAGCUUGAACAGUCU    72.4％    2197    UAAUAAGAGCUUUGACAUU    71.9％

2139    AAGAAAAAGGAGAGUAAGA    72.4％    2198    CAAAGAGUGAAUAAGAGAG    71.9％

2140    GAGUGAAUAAGAGAGGCUA    72.3％    2199    CUUGUUCGAGAAAUUUUUC    71.9％

2141    GGCAAAAGAAAUACACCAA    72.3％    2200    GCUGCAACUUGUUCGAGAA    71.9％

2142    CAUGUUCGAGAGUAAGAGA    72.3％    2201    UCAUGCCUUGAAACAAUGG    71.9％

2143    AAAAAACAAAGAGUGAAUA    72.3％    2202    CAUGCCUUGAAACAAUGGA    71.9％

2144    AGAGUGAAUAAGAGAGGCU    72.3％    2203    AAAUGGCAAGACUAGGAAA    71.9％

2145    GAAAAAACAAAGAGUGAAU    72.3％    2204    CAAAAUGGCAAGACUAGGA    71.9％

2146    CUGUGGGAUCAAACCCAAU    72.2％    2205    UCUGGACGGAUUAAGAAGG    71.9％

2147    GGGAAUCAACAUGAGCAAA    72.2％    2206    AAAGAGUGAAUAAGAGAGG    71.9％

2148    GUGUCCUGGAGGCUAUGGC    72.2％    2207    ACAGGAACAGGGUACACCA    71.8％

2149    AAAAAGGAGAGUAAGAGAC    72.2％    2208    CACUUUCAAAGAAAAAGGA    71.8％

2150    UCUGUAAACAAUGCUGUAG    72.2％    2209    CAACACUAAGUGGAAUGAA    71.8％

2151    GUGGGAUCAAACCCAAUCA    72.2％    2210    GACAACACUAAGUGGAAUG    71.8％

2152    AAGAUCAUUCGAGCUAAAG    72.2％    2211    ACAACACUAAGUGGAAUGA    71.8％

2153    UGUGUCCUGGAGGCUAUGG    72.2％    2212    UGGACGGAUUAAGAAGGAA    71.8％

2154    UGUGGGAUCAAACCCAAUC    72.2％    2213    ACACUUUCAAAGAAAAAGG    71.8％

2155    CUGUAAACAAUGCUGUAGU    72.2％    2214    AAAACAAAGAGUGAAUAAG    71.8％

2156    GAACUCAUGCCUUGAAACA    72.2％    2215    CAGGAACAGGGUACACCAU    71.8％

2157    GUUUUGGAGUGUCUGGAAU    72.2％    2216    UAUGGAAUAUGAUGCCGUU    71.8％

2158    CAUGAGCAAAAAGAAGUCC    72.1％    2217    ACUUUCAAAGAAAAAGGAG    71.8％

2159    GGAUGAUGAUGGGCAUGUU    72.1％    2218    GAGUCAGCUGAUAUGAGCA    71.7％

2160    AACAAAGAGUGAAUAAGAG    72.1％    2219    AGAGCUUUGACAUUGAACA    71.7％

2161    ACAAAGAGUGAAUAAGAGA    72.1％    2220    AUAAGAGCUUUGACAUUGA    71.7％

2162    AAACAAAGAGUGAAUAAGA    72.1％    2221    GGACGGAUUAAGAAGGAAG    71.7％

2163    GGGAUGAUGAUGGGCAUGU    72.1％    2222    GAGAGUAAGAGACAACAUG    71.7％

2164    AAAAGGAUAUAUGUUCGAG    72.1％    2223    AAGAGCUUUGACAUUGAAC    71.7％

2165    ACUAGGAAAAGGAUACAUG    72.1％    2224    GUCUGGACGGAUUAAGAAG    71.7％

2166    CUUUUGAGAACCAUGCCUU    72.0％    2225    GAUGGGCUCCAAUCCUCCG    71.7％

2167    AGACXGUGUCCUGGAGGCU    72.0％    2226    AAGCUGUGGAAUCAAACCC    71.7％

2168    GACUAGGAAAAGGAUACAU    72.0％    2227    UAAGAGCUUUGACAUUGAA    71.7％

2169    CCCAACUCAACCCAAUUGA    72.0％    2228    CUUUCAAAGAAAAAGGAGA    71.7％

2170    AAAAACAAAGAGUGAAUAA    72.0％    2229    AUGGGCUCCAAUCCUCCGA    71.7％

2171    UUGUUCGAGAAAUUUUUCC    72.0％    2230    GGAUGGGCUCCAAUCCUCC    71.7％

2172    AGUCCUAUAUAAAUAAAAC    72.0％    2231    GACGGAUUAAGAAGGAAGA    71.7％

2173    AACUUGUUCGAGAAAUUUU    72.0％    2232    AGUCAGCUGAUAUGAGCAU    71.7％

2174    CCCCAACUCAACCCAAUUG    72.0％    2233    ACAAAUACAGAAACUGGGG    71.6％

2175    AAGUCCUAUAUAAAUAAAA    72.0％    2234    GGAACAGGGUACACCAUGG    71.6％

2176    ACUGUGUCCUGGAGGCUAU    72.0％    2235    AGCUGUGGGAUCAAACCCA    72.6％

2236    CAAAUACAGAAACUGGGGC    71.6％    2295    UGAGCAUCGCACCAAUAAU    70.9％

2237    GUCAGCUGAUAUGAGCAUU    71.6％    2296    CGCACCAAUAAUGUUCUCA    70.9％

2238    CUGCAACUUGUUCGAGAAA    71.6％    2297    UUAGCUAGAAGCAUUUGCG    70.9％

2239    GAACAGGGUACACCAUGGA    71.6％    2298    CAUCGCACCAAUAAUGUUC    70.9％

2240    AAGAGUGAAUAAGAGAGGC    71.6％    2299    GAGCAUCGCACCAAUAAUG    70.9％

2241    AGUGCUGCAACUUGUUGGA    71.5％    2300    UCUCGAUACUGAAUCUUGG    70.8％

2242    CUUUCACAAUCACUGGGGA    71.5％    2301    AGACGAGAAGAUCAUUCGA    70.8％

2243    CUCAUGCCUUGAAACAAUG    71.5％    2302    GGUAAUGAAAAGAAGGCCA    70.8％

2244    UCUUUCACAAUCACUGGGG    71.5％    2303    CAGACGAGAAGAUCUUUCG    70.8％

2245    AAGUGCUGCAACUUGUUCG    71.5％    2304    GUCUCGAUACUGAAUCUUG    70.8％

2246    AGGAACAGGGUACACCAUG    71.5％    2305    UUUAGCUAGAAGCAUUUGC    70.8％

2247    AUGCCUUGAAACAAUGGAA    71.4％    2306    GUAAUGAAAAGAAGGCCAA    70.8％

2248    AAUAAAGAGCUUUGACAUG    71.4％    2307    ACUUUAGCUAGAAGCAUUU    70.8％

2249    CAGUUUUGGAGUGUCUGGA    71.4％    2308    AGCCCAUGGUCCAGCCAAA    70.8％

2250    AAAGAAGGCCAAACUGGCA    71.4％    2309    UAAUGAAAAGAAGGCCAAA    70.7％

2251    AUCAAAGACUACAGAUAUA    71.4％    2310    GAGUCUCGAUACUGAAUCU    70.7％

2252    CCUUUGUCAGCCAUAAAGA    71.4％    2311    UCAGACGAGAAGAUCAUUC    70.7％

2253    GUAUGGAAUAUGAUGCCGU    71.4％    2312    UCGUUCAACAAACAAGGGU    70.7％

2254    UUGGCGAUGAUUACAUAUA    71.4％    2313    AUUCAGACGAGAAGAUCAU    70.7％

2255    GAAAAGAAGGCCAAACUGG    71.4％    2314    UGCCAUAGAGGAGACACAC    70.7％

2256    CAUCAAAGACUACAGAUAU    71 4％    2315    CCCAUGGUCCAGCCAAAAG    70.7％

2257    CCCUUGUCAGCCAUAAAAG    71.4％    2316    GGAGUCUCGAUACUGAAUC    70.7％

2258    UUGUUCAUCAAAGACUACA    71.4％    2317    UGACAAAGAUGCAGAGGAG    70.6％

2259    AAAAGAAGGCCAAACUGGC    71.4％    2318    CACAAAUUCAGACGAGAAG    70.6％

2260    GCCCAUGGUCCAGCCAAAA    71.2％    2319    CUGAGCAUCGCACCAAUAA    70.6％

2261    ACAACAUACUGGUGGGAUG    71.2％    2320    CCAAAGAUGCAGAGAGAGG    70.6％

2262    GUGCUGCAACUUGUUCGAG    71.2％    2321    AGUCUCGAUACUGAAUCUU    70.6％

2263    AGUAUGGAAUAUGAUGCCG    71.2％    2322    CAACAAGGAAGAAAAUUGA    70.6％

2264    CAACAUACUGGUGGGAUGG    71.2％    2323    GCACCCCAACUCAACCCAA    70.6％

2265    AAUCCCUUUGUCAGCCAUA    71.2％    2324    GCCAUAGAGGAGACVCACA    70.6％

2266    UCCCUUUGUCAGCCAUAAA    71.2％    2325    GGCACCCCAACUCAACCCA    70.6％

2267    AUUGUUCAUCAAAGACUAC    71.2％    2326    UAUACAUAUAGGUGCCAUA    70.6％

2268    AUCCCUUUGUCAGCCAUAA    71.2％    2327    AUGACCAAAGAUGCAGAGA    70.6％

2269    UGGCAAGACUAGGAAAAGG    71.1％    2328    GUUGAAACUUUAGCUAGAA    70.6％

2270    UUCUUUCACAAUCACUGGG    71.1％    2329    AUACAUAUAGGUGCCAUAG    70.6％

2271    AAUGGCAAGACUAGGAAAA    71.1％    2330    GUCGUUCAACAAACAAGGG    70.5％

2272    UUUCACAAUCACUGGGGAC    71.1％    2331    ACAAAUUCAGACGAGAAGA    70.5％

2273    UCGCACCAAUAAUGUUCUC    71.1％    2332    ACAAGGAAGAAAAUUGAGA    70.5％

2274    GCACCAAUAAUGUUCUCAA    71.1％    2333    UCCUGAGCAUCGCACCAAU    70.5％

2275    ACCAAUAAUGUUCUCAAAC    71.1％    2334    AUCCUGAGCAUCGCACCAA    70.5％

2276    UUCACAAUCACUGGGGACA    71.1％    2335    GGGGACAACACUAAGUGGA    70.5％

2277    UCACAAUCACUGGGGACAA    71.1％    2336    AUAGAGGAGACACACAAAU    70.5％

2278    CACCAAUAAUGUUCUCAAA    71.1％    2337    GGGACAACACUAAGUGGAA    70.5％

2279    AUGGCAAGACUAGGAAAAG    71.1％    2338    CCAUAGAGGAGACACACAA    70.5％

2280    ACUUAUGAUUGGACAUUAA    71.0％    2339    ACCAAAGAUGCAGAGAGAG    70.5％

2281    GCUUUGACAUUGAACACGA    71.0％    2340    ACACAAAUUCAGACGAGAA    70.5％

2282    GAAGUCGUUCAACAAACAA    71.0％    2341    UCAACAAGGAAGAAAAUUG    70.5％

2283    AGCUUUGACAUUGAACACG    71.0％    2342    GACGAGAAGAUCAUUCGAG    70.5％

2284    AAGUCGUUUCAACAAAAAG    71.0％    2343    GUUCAUCAAAGACUACAGA    70.5％

2285    UAGCUAGAAGCAUUUGCGA    710％     2344    AAAUUCAGACGAGAAGAUC    70.5％

2286    UUUGACAUUGAACACGAUG    71.0％    2345    CAUAGAGGAGACACACAAA    70.5％

2287    CUUUGACAUUUGAACCGAU    71.0％    2346    CAAAUUCAGACGAGAAGAU    70.5％

2288    AUCGCACCAAUAAUGUUCU    71.0％    2347    GGACAACACUAAGUGGAAU    70.5％

2289    CUUUAGCUAGAAGCAUUUG    71.0％    2348    AAUUCAGACGAGAAGAUCA    70.5％

2290    CUUAUGAUUGGACAUUAAA    71.0％    2349    GACCAAAGAUGCAGAGAGA    70.5％

2291    GAACACAAAUACCCGCAGA    71.0％    2350    AACUUUAGCUAGAAGCAUU    70.4％

2292    AGCAUCGCACCAAUAAUGU    70.9％    2351    AUGAAAAGAAGGCCAAACU    70.4％

2293    GCAUCGCACCAAUAAUGUU    70.9％    2352    CACCCCAACUCAACCCAAU    70.4％

2294    UUCAGACGAGAAGAUCAUU    70.9％    2353    UACUGAAUCUUGGGCAAAA    70.4％

2354    ACCCCAACUCAACCCAAUU    70.4％    2372    AAGAGCUGUGGGAAUCAAA    70.2％

2355    AAUGAAAAGAAGGCCAAAC    70.4％    2373    CACAUAUACCCGCAGAAAU    70.2％

2356    UGAAACUUUAGCUAGAAGC    70.4％    2374    UGAAAAGAAGGCCAAACUG    70.2％

2357    UUGAAACUUUAGCUAGAAG    70.4％    2375    UAAAGAAGCUGUGGGAUCA    70.1％

2358    AACAAGGAAGAAAAUUGAG    70.4％    2376    AAAGAAGCUGUGGGAUCAA    70.1％

2359    GAAACUUUAGCUAGAAGCA    70.4％    2377    CACACAAAUUCAGACGAGA    70.1％

2360    UAGAGGAGACACACAAAUU    70.4％    2378    CAAAUACCCGCAGAAAUGC    70.1％

2361    AAACUUUAGCUAGAAGCAU    70.4％    2379    UUGGAGUGUCUGGAAUAAA    70.1％

2362    CCUGAGCAUCGCACCAAUA    70.3％    2380    UAUUUCAAUGAAUCAACAA    70.1％

2363    AUCAACAAGGAAGAAAAUU    70.3％    2381    UUUGGAGUGUCUGGAAUAA    70.1％

2364    AUACUGAAUCUUGGGCAAA    70.3％    2382    AAAUACCCGCAGAAAUGCU    70.1％

2365    CGAACACAAAUACCCGCAG    70.3％    2383    AACACAAAUACCCGCAGAA    70.1％

2366    AAUCAACAAGGAAGAAAAU    70.3％    2384    CAUCCUGAGCAUCGCACCA    70.1％

2367    ACAAAUACCCGCAGAAAUG    70.2％    2385    AAAUACAGAAACUGGGGCA    70.0％

2368    AGAAGCUGUGGGAUCAAAC    70.2％    2386    CUGCAUUAGCCAACACCAU    70.0％

2369    ACUGAAUCUUGGGCAAAAG    70.2％    2387    ACUGCAUUAGCCAACACCA    70.0％

2370    ACACAAAUACCCGCAGAAA    70.2％    2388    AAUACAGAAACUGGGGCAC    70.0％

2371    GAAUCAACAAGGAAGAAAA    70.2％    2389    AGUCGUUCAACAAACAAGG    70.0％

表2-3在表1-3所列甲型流感片段2(PA)序列中以至少70％存在的保守19-mer序列

Seq ID    序列              百分比    2421  GAGGAGUGCCUGAUUAAUG  96.9％

2390   UUAGAGCCUAUGUGGAUGG  98.9％    2422  AGUGCCUGAUUAAUGAUCC  96.9％

2391   UUUAGAGCCUAUGUGGAUG  98.9％    2423  UAUGAAGCAAUUGAGGAGU  96.4％

2392   AGCAAUUGAGGAGUGCCUG  98.7％    2424  AUAUGAAGCAAAUGAGGAG  96.4％

2393   UUGAGGAGUGCCUGAUUAA  98.7％    2425  AUGAAGCAAUUGAGGAGUG  96.4％

2394   GCAAUUGAGGAGUGCCUGA  98.6％    2426  UGAAGCAAUUGAGGAGUGC  96.4％

2395   AUUGAGGAGUGCCUGAUUA  98.6％    2427  AAGCAAUUGAGGAGUGCCU  96.4％

2396   CAAUUGAGGAGUGCCUGAU  98.6％    2428  GAAGCAAUUGAGGAGUGCC  96.4％

2397   AAUUGAGGAGUGCCUGAUU  98.6％    2429  ACAAAUUUGCAGCAAUAUG  95.4％

2398   UAGAGCCUAUGUGGAUGGA  98.3％    2430  AACAAAUUUGCAGCAAUAU  95.4％

2399   AGAGCCUAUGUGGAUGGAU  98.3％    2431  GGGCUAUAUGAAGGCAUUG  95.3％

2400   GAGCCUAUGUGGAUGGAUU  98.2％    2432  GCUAUAUGAAGCAAUUGAG  95.3％

2401   UAAUGAUCCCUGGGUUUUG  98.0％    2433  UCAUGUAUUCAGAUUUUCA  95.3％

2402   UUAAUGAUCCCUGGGUUUU  98.0％    2434  GGCUAUAUGAAGCAAUUGA  95.3％

2403   AUGAUCCCUGGGUUUUGCU  98.0％    2435  CAAAUUUGCAGCAAUAUGC  95.2％

2404   AAUGAUCCCUGGGUUUUGC  98.0％    2436  AAAUUUGCAGCAAUAUGCA  95.2％

2405   CCUGAUUAAUGAUCCCUGG  97.9％    2437  UUCAUGUAUUCAGAUUUUC  95.2％

2406   UGCCUGAUUAAUGAUCCCU  97.9％    2438  AAUUUGCAGCAAUAUGCAC  95.1％

2407   AUUAAUGAUCCCUGGGUUU  97.9％    2439  ACAAACAAAUUUGCAGCAA  95.0％

2408   GCCUGAUUAAUGAUCCCUG  97.9％    2440  CAAACAAAUUUGCAGCAAU  95.0％

2409   CUGAUUAAUGAUCCCUGGG  97.9％    2441  AAACAAAUUUGCAGCAAUA  95.0％

2410   GAUUAAUGAUCCCUGGGUU  97.8％    2442  UUUUAGAGCCUAUGUGGAU  94.9％

2411   UGAUUAAUGAUCCCUGGGU  97.8％    2443  AAUUUUAGAGCCUAUGUGG  94.7％

2412   UAUAUGAAGCAAUUGAGGA  97.3％    2444  AUUUUAGAGCCUAUGUGGA  94.7％

2413   CUAUAUGAAGCAAUUGAGG  97.2％    2445  GUAUUCAGAUUUUCAUUUC  94.6％

2414   CUUGGUUCAACUCCUUCCU  97.1％    2446  GCAUCCUGUGCAGCAAUGG  94.6％

2415   UCUUGGUUCAACUCCUUCC  97.1％    2447  AUGCAUCCUGUGCAGCAAU  94.6％

2416   AGGAGUGCCUGAUUAAUGA  96.9％    2448  UAUUCAGAUUUUCAUUUCA  94.6％

2417   GAGUGCCUGAUUAAUGAUC  96.9％    2449  GAAACAAACAAAUUUGCAG  94.6％

2418   UGAGGAGUGCCUGAUUAAU  96.9％    2450  UGUAUUCAGAUUUUCAUUU  94.6％

2419   GUGCCUGAUUAAUGAUCCC  96.9％    2451  AAUGCAUCCUGUGCAGCAA  94.6％

2420   GGAGUGCCUGAUUAAUGAU  96.9％    2452  AACAAACAAAUUUGCAGCA  94.6％

2453    AAACAAACAAAUUUGCAGC    94.6％    2504    CGUCAGUCCGAAAGAGGCG    92.4％

2454    CAUCCUGUGCAGCAAUGGA    94.6％    2505    GUCAGUCCGAAAGAGGCGA    92.4％

2455    AUUCAGAUUUUCAUUUCAU    94.6％    2506    UCAGUCCGAAAGAGGCGAA    92.4％

2456    AUGUAUUCAGAUUUUCAUU    94.6％    2507    GGUAAACUUUGUGAGCAUG    92.4％

2457    UGCAUCCUGUGCAGCAAUG    94.6％    2508    UCCGAAAGAGGCGAAGAAA    92.4％

2458    CAUGUAUUCAGAUUUUCAU    94.3％    2509    CCGAAAGAGGCGAAGAAAC    92.4％

2459    AGAAUUUUAGAGCCUAUGU    94.3％    2510    UUUCGUCAGUCCGAAAGAG    92.4％

2460    GAGAAUUUUAGAGCCUAUG    94.2％    2511    UCCUUUCGUCAGUCCGAAA    92.3％

2461    GAUUUUCAUUUCAUCAAUG    94.2％    2512    CCUUUCGUCAGUCCGAAAG    92.3％

2462    UGAGAAUUUUGAGGCCUAU    94.2％    2513    GCGAUUUGAAGCAAUAUGA    92.3％

2463    UUGAGAAUUUUAGAGCCUA    94.2％    2514    CUUUCGUCAGUCCGAAAGA    92.3％

2464    AUUUUCAUUUCAUCAAUGA    94.2％    2515    AAGCGAUUUGAAGCAAUAU    92.1％

2465    UCAGAUUUUCAUUUCAUCA    94.1％    2516    AAGAUUUUGUGCGACAAUG    92.0％

2466    GAAUUUUAGAGCCUAUGUG    94.1％    2517    AGCGAUUUGAAGCAAUAUG    92.0％

2467    CAGAUUUUCAUUUCAUCAA    94.1％    2518    GUCCGAAAGAGGCGAAGAA    91.8％

2468    GUUCAGGCUCUUAGGGACA    94.1％    2519    GGCAAGCUUUCUCAAAUGU    91.5％

2469    UUCAGGCUCUUAGGGACAA    94.1％    2520    ACAUUCUUUGGAUGGAAAG    91.3％

2470    AGAUUUUCAUUUCAUCAAU    94.1％    2521    CAUUCUUUGGAUGGAAAGA    91.3％

2471    UUCAGAUUUUCAUUUCAUC    94.0％    2522    GAUUUGAAGCAAUAUGAUA    91.2％

2472    AGAGGCGAAGAAACAAUUG    93.7％    2523    AGGGCAAGCUUUCUCAAAU    91.2％

2473    GAGGCGAAGAAACAAUUGA    93.7％    2524    UUGAGGGCAAGCUUUCUCA    91.2％

2474    GGCGAAGAAACAAUUGAAG    93.5％    2525    AUUUGAAGCAAUAUGAUAG    91.2％

2475    CGAAGAAACAAUUGAAGAA    93.5％    2526    AUUGAGGGCAAGCUUUCUC    91.2％

2476    GCGAAGAAACAAUUGAAGA    93.5％    2527    GAGGGCAAGCUUUCUCAAA    91.2％

2477    AGGCGAAGAAACAAUUGAA    93.5％    2528    GGGCAAGCUUUCUCAAAUG    91.2％

2478    GAAGAAACAAUUGAAGAAA    93.5％    2529    CAUUGAGGGCAAGCUUUCU    91.2％

2479    AAAUGAAAUGGGGAAUGGA    93.4％    2530    GCAAGCUUUCUCAAAUGUC    91.0％

2480    AAAAUGAAAUGGGGAAUGG    93.4％    2531    UGAGGGCAAGCUUUCUCAA    91.0％

2481    UGAAAUGGGGAAUGGAGAU    93.3％    2532    CAGAAUGAGUUCAACAAGG    91.0％

2482    AAUGGGGAAUGGAGAUGAG    93.3％    2533    AGAAUGAGUUCAACAAGGC    91.0％

2483    CACAUUUUCUCAUUCACUG    93.3％    2534    AUAAGCGAUUUGAAGCAAU    90.7％

2484    AAAUGGGGAAUGGAGAUGA    93.3％    2535    UUCUUUGGAUGGAAAGAAC    90.5％

2485    GAAAUGGGGAAUGGAGAUG    93.3％    2536    CGAUUUGAAGCAAUAUGAU    90.5％

2486    AUGAAAUGGGGAAUGGAGA    93.3％    2537    UCUUUGGAUGGAAAGAACC    90.5％

2487    ACAUUUUCUCAUUCACUGG    93.2％    2538    AGCCUAUGUGGAUGGAUUC    90.4％

2488    AAAGAGGCGAAGAAACAAU    92.8％    2539    CAAUGAAAGAGUAUGGAGA    90.4％

2489    GAAAGAGGCGAAGAAACAA    92.8％    2540    UGAAGCAAUAUGAUAGUGA    90.2％

2490    AAUGAAAUGGGGAAUGGAG    92.8％    2541    UGGAAGUUUUGUGCGGACA    90.1％

2491    UAAACUUUGUGAGCAUGGA    92.5％    2542    AUGGAAGAUUUUGUGCGAC    90.1％

2492    AAGAGGCGAAGAAACAAUU    92.5％    2543    AAAGAGUUUUUUGAGAAUA    90.1％

2493    GUAAACUUUGUGAGCAUGG    92.5％    2544    UAAUGAAGGGGGUAUACAU    90.0％

2494    CAGUCCGAAAGAGGCGAAG    92.5％    2545    GAAGAUUUUGUGCGACAAU    90.0％

2495    AGUCCGAAAGAGGCGAAGA    92.5％    2546    UCUGGAUAGAGCUCGAUGA    89.9％

2496    CGAAAGAGGCGAAGAAACA    92.4％    2547    AUAAUGAAGGGGGUAUACA    89.9％

2497    UGGUAAACUUUGUGAGCAU    92.4％    2548    AUUCUUUGGAUGGAAAGAA    89.9％

2498    GUGGUAAACUUUGUGAGCA    92.4％    2549    UUGAAGCAAUAUGAUAGUG    89.9％

2499    UUUGUGCGACAAUGCUUCA    92.4％    2550    GAGAAACACAUGACCAAAG    89.6％

2500    UCGUCAGUCCGAAAGAGGC    92.4％    2551    UUUGAAGCAAUAUGAUAGU    89.6％

2501    UUGUGCGACAAUGCUUCAA    92.4％    2552    AGAAAGACAUGACCAAAGA    89.4％

2502    UAAGCGAUUUGAAGCAAUA    92.4％    2553    GAUUUUGUGCGACAAUGCU    89.4％

2503    UUCGUCAGUCCGAAAGAGG    92.4％    2554    AUUUUGUGCGACAAUGCUU    89.4％

2555    UGAAGGGGGUAUACAUUAA    89.3％    2606   GGGGGUAUACAUUAAUACU    87.0％

2556    AGAUUUUGUGCGACAAUGC    89.2％    2607   GGAUGGAUUCGAACCGAAC    87.0％

2557    GGAAGAUUUUGUGCGACAA    89.2％    2608   UGUGGAUGGAUUCGAACCG    87.0％

2558    AUGAAGGGGGUAUACAUUA    89.2％    2609   CUUGAGAAUUUUAGAGCCU    86.9％

2559    AAUGAAGGGGGUAUACAUU    89.2％    2610   GCCUUGAGAAUUUUAGAGC    86.9％

2560    CCUAUGUGGAUGGAUUCGA    89.2％    2611   CUGCCUUGAGAAUUUUAGA    86.9％

2561    CUAUGUGGAUGGAUUCGAA    89.2％    2612   UCCUGCCUUGAGAAUUUUA    86.9％

2562    AUGUGGAUGGAUUCGAACC    89.1％    2613   UGUGCAGCAAUGGACGAUU    86.9％

2563    UAUGUGGAUGGAUUCGAAC    89.1％    2614   GUGCAGCAAUGGACGAUUU    86.9％

2564    AAAGACAUGACCAAAGAGU    89.0％    2615   UUCUCCUGCCUUGAGAAUU    86.9％

2565    AACAUUCUUUGGAUGGAAA    89.0％    2616   CUCCUGCCUUGAGAAUUUU    86.9％

2566    AAGACAUGACCAAAGAGUU    89.0％    2617   UGCCUUGAGAAUUUUAGAG    86.9％

2567    UUUUGUGCGACAAUGCUUC    88.9％    2618   UCUCCUGCCUUGAGAAUUU    86.9％

2568    GCCUAUGUGGAUGGAUUCG    88.7％    2619   CCUGCCUUGAGAAUUUUAG    86.9％

2569    GGGAUUCCUUUCGUCAGUC    88.4％    2620   CCUUGAGAAUUUUAGAGCC    86.9％

2570    UGGGAUUCCUUUCGUCAGU    88.4％    2621   UGCAUUGAGGGCAAGCUUU    86.8％

2571    GAAAGACAUGACCAAAGAG    88.4％    2622   GGCCUCUGGGAUUCCUUUC    86.8％

2572    GCAAUGAAAGAGUAUGGAG    88.3％    2623   GCAUUGAGGGCAAGCUUUC    86.8％

2573    AUUCCUUUCGUCAGUCCGA    88.1％    2624   AUCCUGUGCAGCAAUGGAC    86.8％

2574    GAUUCCUUUCGUCAGUCCG    88.1％    2625   UCCUGUGCAGCAAUGGACG    86.7％

2575    GGAUUCCUUUCGUCAGUCC    88.1％    2626   AGAGGCCUCUGGGAUUCCU    86.6％

2576    AAGGGGGUAUACAUUAAUA    87.8％    2627   AGGCCUCUGGGAUUCCUUU    86.6％

2577    GAAGGGGGUAUACAUUAAU    87.8％    2628   CUUCUCCUGCCUUGAGAAU    86.6％

2578    AAUGAAAGAGUAUGGAGAG    87.8％    2629   GCCUCUGGGAUUCCUUUCG    86.6％

2579    AGGGGGUAUACAUUAAUAC    87.8％    2630   GAGGCCUCUGGGAUUCCUU    86.6％

2580    UGUAUGAUUACAAGGAGAA    87.7％    2631   CCUGUGCAGCAAUGGACGA    86.6％

2581    CCGAACUUCUCCUGCCUUG    87.4％    2632   CCUCUGGGAUUCCUUUCGU    86.5％

2582    CGAACUUCUCCUGCCUUGA    87.4％    2633   CUGGGAUUCCUUUCGUCAG    86.5％

2583    AACUUCUCCUGCCUUGAGA    87.3％    2634   CUGUGCAGCAAUGGACGAU    86.4％

2584    GAACUUCUCCUGCCUUGAG    87.3％    2635   GGAUUCGAACCGAACGGCU    86.2％

2585    AAAGAGAAAGACAUGACCA    87.3％    2636   UGGAUUCGAACCGAACGGC    86.2％

2586    AUGGAUUCGAACCGAACGG    87.2％    2637   CAGAGGCCUCUGGGAUUCC    86.1％

2587    AAGAGAAAGACAUGACCAA    87.2％    2638   ACGGCUGCAUUGAGGGCAA    86.0％

2588    CUCUGGGAUUCCUUUCGUC    87.2％    2639   AACGGCUGCAUUGAGGGCA    86.0％

2589    GAUGGAUUCGAACCGAACG    87.2％    2640   GCUGCAUUGAGGGCAAGCU    85.8％

2590    GGGUAUACAUUAAUACUGC    87.2％    2641   UUCCUUUCGUCAGUCCGAA    85.8％

2591    GGGGUAUACAUUAAUACUG    87.2％    2642   CUGCAUUGAGGGCAAGCUU    85.8％

2592    AAGCUUUCUCAAAUGUCCA    87.1％    2643   GGCUGCAUUGAGGGCAAGC    85.8％

2593    AGCUUUCUCAAAUGUCCAA    87.1％    2644   CGGCUGCAUUGAGGGCAAG    85.8％

2594    ACAUGACCAAAGAGUUUUU    87.1％    2645   UUGUAUGAUUACAAGGAGA    85.8％

2595    AGAGAAAGACAUGACCAAA    87.1％    2646   AUAGUGACGAACCUGAAUU    85.7％

2596    UCUGGGAUUCCUUUCGUCA    87.1％    2647   GGGGCUAUAUGAAGCAAUU    85.6％

2597    ACUUCUCCUGCCUUGAGAA    87.1％    2648   UGACCAAAGAGUUUUUUGA    85.6％

2598    GACAUGACCAAACAGUUUU    87.1％    2649   UUGUUCAGGCUCUUAGGGA    85.5％

2599    AGACAUGACCAAAGAGUUU    87.1％    2650   CAUGACCAAAGAGUUUUUU    85.5％

2600    GUGGAUGGAUUCGAACCGA    87.0％    2651   AUGACCAAAGAGUUUUUUG    85.5％

2601    AAGCACAGAUUUGAAAUAA    87.0％    2652   UUUUCUCAUUCACUGGGGA    85.4％

2602    AGCACAGAUUUGAAUUAAU    87.0％    2653   UGUUCAGGCUCUUAGGGAC    85.4％

2603    CAAGCUUUCUCAAAUGUCC    87.0％    2654   GACCAAAGAGUUUUUUGAG    85.4％

2604    GCUUUCUCAAAUGUCCAAA    87.0％    2655   CAUUUUCUCAUUCACUGGG    85.4％

2605    UGGAUGGAUUCGAACCGAA    87.0％    2656   AUUUUCUCAUUCACUGGGG    85.4％

2657   AAGCAAUAUGAUAGUGACG  85.4％    2708    ACGAACCUGAAUUAAGGUC  84.1％

2658   GAUAGUGACGAACCUGAAU  85.4％    2709    AUGUUCUUGUAUGUGAGGA  84.1％

2659   AGCAAUAUGAUAGUGACGA  85.3％    2710    UUUUCUCUCACUGACCCGA  84.1％

2660   ACCAAAGAGUUUUUUGAGA  85.2％    2711    AACAGAGGCCUCUGGGAUU  84.1％

2661   CUUGCCGACCAAAGUCUCC  85.2％    2712    UUUCUCUCACUGACCCGAG  84.1％

2662   UUGCCGACCAAAGUCUCCC  85.2％    2713    GAACGGCUGCAUUGAGGGC  84.1％

2663   UAUGAUAGUGACGAACCUG  85.1％    2714    UGUUCUUGUAUGUGAGGAC  84.1％

2664   AAUAUGAUAGUGACGAACC  85.1％    2715    AAUAAAUUAAAUCUGAGGA  84.0％

2665   UGAUAGUGACGAACCUGAA  85.1％    2716    GACGAACCUGAAUUAAGGU  84.0％

2666   AUGAUAGUGACGAACCUGA  85.1％    2717    AUAAAAUUAAAUCUGAGAA  84.0％

2667   CAAUAUGAUAGUGACGAAC  85.1％    2718    GCCAACAGAGGCCUCUGGG  83.9％

2668   UUGAUGAUCCAAAUGCACU  85.1％    2719    UGGCCAACAGAGGCCUCUG  83.9％

2669   CUUUCUCAAAUGUCCAAAG  85.0％    2720    CUAAGAAGUGCCAUAGGCC  83.9％

2670   UCAAUAGCCUGUAUGCAUC  85.0％    2721    CCAACAGAGGCCUCUGGGA  83.9％

2671   AAGGCCUAUGUUCUUGUAU  85.0％    2722    CAACAGAGGCCUCUGGGAU  83.9％

2672   AAAUGGGAGAAAUACUGUG  85.0％    2723    GGCCAACAGAGGCCUCUGG  83.9％

2673   AUAUGAUAGUGACGAACCU  85.0％    2724    AUGGCCAACAGAGGCCUCU  83.8％

2674   AAUGGGAGAAAUACUGUGU  85.0％    2725    UUCUUGUAUGUGAGGACAA  83.8％

2675   CUUGAUGAUCCAAAUGCAC  85.0％    2726    UCUUGUAUGUGAGGACAAA  83.8％

2676   UUCAAUAGCCUGUAUGCAU  85.0％    2727    AAAAGGCCAAUAAAAUUAA  83.7％

2677   GAAGCAAUAUGAUAGUGAC  85.0％    2728    AGGCCAAUAAAAUUAAAUC  83.7％

2678   GCUUGCCGACCAAAGUCUC  84.9％    2729    AAAGGCCAAUAAAAUUAAA  83.7％

2679   CAAGGCCUAUGUUCUUGUA  84.9％    2730    GAAAAGGCCAAUAAAAUUA  83.7％

2680   GCAAUAUGAUAGUGACGAA  84.9％    2731    CGAACCUGAAUUAAGGUCA  83.7％

2681   UCAAGGCCUAUGUUCUUGU  84.9％    2732    UUUUUUGAGAAUAAAUCAG  83.7％

2682   CCAAAGAGUUUUUUGAGAA  84.8％    2733    AAGGCCAAUAAAAUUAAAU  83.7％

2683   AGGCCUAUGUUCUUGUAUG  84.8％    2734    GUUUUUGUAUGUGAGGACA  83.6％

2684   UAAGAAGUGCCAUAGGCCA  84.8％    2735    UUUUUGAGAAUAAAUCAGA  83.6％

2685   GGCCUAUGUUCUUGUAUGU  84.6％    2736    UUUUGAGAAUAAAUCAGAA  83.5％

2686   CUCAAAUGUCCAAAGAAGU  84.6％    2737    GUUUUUUGAGAAUAAAUCA  83.3％

2687   UCUCAAAUGUCCAAAGAAG  84.6％    2738    AGUUUUUUGAGAAUAAAUC  83.3％

2688   UUUCUCAAAUGUCCAAAGA  84.5％    2739    AAGAGUUUUUUGAGAAUAA  83.3％

2689   AACCGAACGGCUGCAUUGA  84.4％    2740    GAGUUUUUUGAGAAUAAAU  83.3％

2690   CCAAUAAAAUUAAAUCUGA  84.4％    2741    AGUGACGAACCUGAAUUAA  83.2％

2691   GCCAAUAAAAUUAAAUCUG  84.4％    2742    GUGACGAACCUGAAUUAAG  83.2％

2692   UUCUCAAAUGUCCAAAGAA  84.3％    2743    AAAUGGCCAACAGAGGCCU  83.2％

2693   AGGCUUGCCGACCAAAGUC  84.3％    2744    GGGGGCUAUAUGAAGCAAU  83.2％

2694   AGGUCACUUUCAAGCUGGA  84.3％    2745    GAAAUGGCCAACAGAGGCC  83.2％

2695   CUAUGUUCUUGUAUGUGAG  84.3％    2746    CAAAGAGUUUUUUGAGAAU  83.2％

2696   GGUCACUUUCAAGCUGGAU  84.3％    2747    AGAGUUUUUUGAGAAUAAA  83.2％

2697   UGUGGUAAACUUUGUGAGC  84.3％    2748    UGGACAGUAGUAAACAGUA  83.0％

2698   CGAACGGCUGCAUUGAGGG  84.3％    2749    GGACAGUAGUAAACAGUAU  83.0％

2699   AUGUGGUAAACUUUGUGAG  84.3％    2750    GGCCAAUAAAAUUAAAUCU  82.9％

2700   CCUAUGUUCUUGUAUGUGA  84.3％    2751    ACAAUGGCCUGGACAGUAG  82.9％

2701   GAUGUGGUAAACUUUGUGA  84。3％   2752    CAAUGGCCUGGACAGUAGU  82.9％

2702   GGCUUGCCGACCAAAGUCU  84.3％    2753    GCCUGGACAGUAGUAAACA  82.8％

2703   CCGAACGGCUGCAUUGAGG  84.2％    2754    AUGGCCUGGACAGUAGUAA  82.8％

2704   CAAUAAAAUUAAAUCUGAG  84.2％    2755    UGGCCUGGACAGUAGUAAA  82.8％

2705   GCCUAUGUUCUUGUAUGUG  84.2％    2756    ACAUAAGCGAUUUGAAGCA  82.8％

2706   ACAGAGGCCUCUGGGAUUC  84.1％    2757    GGGGGGCUAUAUGAAGCAA  82.8％

2707   ACCGAACGGCUGCAUUGAG  84.1％    2758    GGCCUGGACAGUAGUAAAC  82.8％

2759    GGAGAAAUACUGUGUCCUU    82.7％    2810    UGCAGAACUAAAGAGGGAA    82.0％

2760    GACAUAAGCGAUUUGAAGC    82.7％    2811    CGAACCGAACGGCUGCAUU    81.9％

2761    AGAAAUACUGUGUCCUUGA    82.7％    2812    CACACGAAAAGGGAAUAAA    81.9％

2762    UGGGAGAAAUACUGUGUCC    82.7％    2813    UUUCAUUUCAUCAAUGAAC    81.9％

2763    GGGAGAAAUACUGUGUCCU    82.7％    2814    UCGAACCGAACGGCUGCAU    81.8％

2764    AGACAUAAGCGAUUUGAAG    82.7％    2815    CCACACGAAAAGGGAAUAA    81.8％

2765    GAGAAAUACUGUGUCCUUG    82.7％    2816    UAGUGACGAACCUGAAUUA    81.8％

2766    CCUGGACAGUAGUAAACAG    82.7％    2817    UUCGAACCGAACGGCUGCA    81.8％

2767    GAGACAUAAGCGAUUUGAA    82.6％    2818    GCAGAACUAAAGAGGGAAG    81.8％

2768    AGAGACAUAAGCGAUUUGA    82.6％    2819    ACACGAAAAGGGAAUAAAU    81.7％

2769    GAGGAAAGCAGGGCUAGGA    82.6％    2820    UCUCUCACUGACCCGAGAC    81.7％

2770    AGGAAAGCAGGGCUAGGAU    82.6％    2821    CUCUCACUGACCCGAGACU    81.7％

2771    AUGGGAGAAAUACUGUGUC    82.6％    2822    UUUCAUGUAUUCAGAUUUU    81.6％

2772    UGAUUGAAGCCGAGUCCUC    82.5％    2823    GUUUCAUGUAUUCAGAUUU    81.6％

2773    UACCUUGAAAAGGCCAAUA    82.5％    2824    UGUUUCAUGUAUUCAGAUU    81.6％

2774    AUGAUUGAAGCCGAGACCU    82.5％    2825    AAAGCACAGAUUUGAAAUA    81.4％

2775    CAUAAGCGAUUUGAAGCAA    82.4％    2826    ACCACACGAAAAGGGAAUA    81.4％

2776    ACCUUGAAAAGGCCAAUAA    82.4％    2827    AAGAAAUGGCCAACAGAGG    81.4％

2777    AACAUGGCACCAGAGAAAG    82.4％    2828    AUUCGAACCGAACGGCUGC    81.4％

2778    UCACAGCAGAGGUGUCCCA    82.4％    2829    CAAGAAAUGGCCAACAGAG    81.4％

2779    CUAAAAACAUGAAGAAAAC    82.4％    2830    UUCAUUUCAUCAAUGAACA    81.4％

2780    UUCACAGCAGAGGUGUCCC    82.4％    2831    UAUGUUCUUGUAUGUGAGG    81.4％

2781    ACAACACCAAGACCAAUCA    82.4％    2832    UAAAGCACAGAUUUGAAAU    81.4％

2782    ACAUGGCACCAGAGAAAGU    82.4％    2833    GAUUCGAACCGAACGGCUG    81.4％

2783    AAUGGCCAACAGAGGCCUC    82.3％    2834    AUUUCAUCAAUGAACAAGG    81.3％

2784    AUGUCCAAAGAAGUGAAUG    82.3％    2835    UCAUUUCAUCAAUGAACAA    81.3％

2785    UUCUCUCACUGACCCGAGA    82.3％    2836    CAUUUCAUCAAUGAACAAG    81.3％

2786    UGUCCAAAGAAGUGAAUGC    82.3％    2837    AACCUGAAUUAAGGUCACU    81.3％

2787    UUGAAAAGGCCAAUAAAAU    82.3％    2838    AAUUAAGGUCACUUUCAAG    81.3％

2788    CAUGGCCCAUUGGGGAGUC    82.3％    2839    GAACCUGAAUUAAGGUCAC    81.3％

2789    AGCCACAUAAAUGGGAGAA    82.2％    2840    UCACUGGGGAGGAAAUGGC    81.2％

2790    AAUGGCCUGGACAGUAGUA    82.2％    2841    CAUUCACUGGGGAGGAAAU    81.2％

2791    CCACAUAAAUGGGAGAAAU    82.2％    2842    UCAUUCACUGGGGAGGAAA    81.2％

2792    ACAUAAAUGGGAGAAAUAC    82.2％    2843    UUCACUGGGGAGGAAAUGG    81.2％

2793    GAGCCACAUAAAUGGGAGA    82.2％    2844    AUUCACUGGGGAGGAAAUG    81.1％

2794    AGCAUGAUUGAAGCCGAGU    82.2％    2845    AAACCACACGAAAAGGGAA    81.1％

2795    UGACGAACCUGAAUUAAGG    82.2％    2846    CACUGGGGAGGAAAUGGCC    81.1％

2796    CAAAUGUCCAAAGAAGUGA    82.2％    2847    AACCACACGAAAAGGGAAU    81.1％

2797    GCAUGAUUGAAGCCGAGUC    82.2％    2848    UGGGGAAUGGAGAUGAGAC    81.0％

2798    UGAAAAGGCCAAUAAAAUU    82.2％    2849    UGAAUUAAGGUCACUUUCA    81.0％

2799    AUAAAUGGGAGAAAUACUG    82.2％    2850    AGCAUUGAAGACCCAAGUC    81.0％

2800    CAUAAAUGGGAGAAAUACU    82.2％    2851    GAAUUAAGGUCACUUUCAA    81.0％

2801    CACAUAAAUGGGAGAAAUA    82.2％    2852    GAAAAACCAAUUUAUAUGG    81.0％

2802    AAAUGUCCAAAGAAGUGAA    82.2％    2853    AUGGGGAAUGGAGAUGAGA    81.0％

2803    UAAAUGGGAGAAAUACUGU    82.2％    2854    CCGAAUUAAGGUCACUUUC    81.0％

2804    AAUGUCCAAAGAAGUGAAU    82.2％    2855    GCAUUGAAGACCCAAGUCA    81.0％

2805    CUUGAAAAGGCCAAUAAAA    82.1％    2856    GGGGAAUGGAGAUGAGACG    81.0％

2806    CUGGACAGUAGUAAACAGU    82.1％    2857    CCUGAAUUAAGGUCACUUU    80.9％

2807    GAACCGAACGGCUGCAUUG    82.1％    2858    CGAAAAACCAAUUUAUAUG    80.8％

2808    UUUUCAUUUCAUCAAUGAA    82.1％    2859    AAGGUCACUUUCAAGCUGG    80.7％

2809    GCCACAUAAAUGGGAGAAA    82.0％    2860    UGGCACCAGAGAAAGUAGA    80.7％

2861  AUGGCACCAGAGAAAGUAG  80.7％    2912  CCCAAGGGAGUGGAAGAAG  79.6％

2862  AGAAAUGGCCAACAGAGGC  80.7％    2913  GACCCAAGUCACGAAGGAG  79.5％

2863  AGAGCAUGAUUGAAGCCGA  80.6％    2914  GGUAUACAUUAAUACUGCC  79.5％

2864  CAUGGCACCAGAGAAAGUA  80.6％    2915  ACCCAAGUCACGAAGGAGA  79.5％

2865  AUUGAAGACCCAAGUCACG  80.6％    2916  UCAAUGCAUCCUGUGCAGC  79.4％

2866  CAUGAAGACCCAAGUCUAC  80.6％    2917  GAGGAAAUGGCCACAAAGG  79.4％

2867  UCUCAUUCACUGGGGAGGA  80.6％    2918  UGGAGAUGAGACGUUGCCU  79.4％

2868  UUCUCAUUCACUGGGGAGG  80.6％    2919  CAAUGCAUCCUGUGCAGCA  79.4％

2869  UUGAAGACCCAAGUCACGA  80.6％    2920  AGGAAAUGGCCACAAAGGC  79.4％

2870  CGGAGUCAAGAAAACUGCU  80.6％    2921  UGCAAGCAUGAGGAGGAAU  79.4％

2871  ACCUGAAUUAAGGUCACUU  80.6％    2922  AUGGAGAUGUGACGUUGCC  79.4％

2872  GAGAGCAUGAUUGAAGCCG  80.6％    2923  CUCAAUGCAUCCUGUGCAG  79.4％

2873  UAAGGUCACUUUCAAGCUG  80.5％    2924  ACAAUUGAAGAAAAAUUUG  79.3％

2874  GCGGAGUCAAUAAAACUGC  80.5％    2925  UGAUGAUCCAAAUGCACUG  79.3％

2875  GCACCAGAGAAAGUAGACU  80.4％    2926  CAAUUUAUGAAAAAUUUGA  79.3％

2876  CACCAGAGAAAGUAGACUU  80.4％    2927  AAUUGAAGAAAAAUUUGAA  79.3％

2877  UUAAAGCACAGAUUUGAAA  80.4％    2928  GCUCAAUGCAUCCUGUGCA  79.3％

2878  GGCACCAGAGAAAGUAGAC  80.4％    2929  UCAAACCACACGAAAAGGG  79.3％

2879  CCAGAGAAAGUAGACUUUG  80.4％    2930  UUAGAAGAAAAUUUGAAAU  79.3％

2880  GAGCAUGAUUGAAGCCGAG  80.4％    2931  GGAGAUGAGACGUUGCCUC  79.3％

2881  ACCAGAGAAAGUAGACUUU  80.3％    2932  AUUGAAGAAAAAUUUGAAA  79.3％

2882  CUCAUUCACUGGGGAGGAA  80.3％    2933  UGCUCAAUGCAUCCUGUGC  79.3％

2883  AACACCAAGACCAAUCAAA  80.3％    2934  GAGAUGAGACGUUGCCUCC  79.2％

2884  UAUAUGAUGCGAUCAAGUG  80.3％    2935  GAAUGGAGAUGAGACGUUG  79.2％

2885  CCUUGAAAAGGCCAAUAAA  80.3％    2936  GAAGACCCAAGUCACGAAG  79.2％

2886  CAGAGAAAGUAGACUUUGA  80.2％    2937  UGUUAAAGCACAGAUUUGA  79.2％

2887  UUUCUCAUUCACUGGGGAG  80.2％    2938  GGAAUGGAGAUGAGACGUU  79.2％

2888  ACACCAAGACCAAUCAAAC  80.2％    2939  UGAAGAAAAAUUUGAAAUC  79.2％

2889  UUAAGGUCACUUUCAAGCU  80.2％    2940  AAGACCCAAGUCACGAAGG  79.2％

2890  CACCAAGACCAAUCAAACU  80.2％    2941  GCAGCAAUGGACGAUUUUC  79.2％

2891  AUUAAGGUCACUUUCAAGC  80.2％    2942  AGAUGAGACGUUGCCUCCU  79.2％

2892  CAACACCAAGACCAAUCAA  80.2％    2943  GUCAACCACACGAAAAGG   79.2％

2893  UUUUCAGCGGAGUCAAGAA  80.1％    2944  CAGCAAUGGACGAUUUUCA  79.2％

2894  ACUAAAAACAUGAAGAAAA  80.1％    2945  UGCAGCAAUGGACGAUUUU  79.2％

2895  CAGCGGAGUCAAGAAAACU  80.1％    2946  GGGAAUGGAGAUGAGGCGU  79.2％

2896  UUUCAGCGGAGUCAAGAAA  80.1％    2947  AUGCACUGUUAAAGCACAG  79.1％

2897  AGCGGAGUCAAGAAAACUG  80.1％    2948  CUGUUAAAGCACAGAUUUG  79.1％

2898  UUCAGCGGAGUCAAGAAAA  80.1％    2949  AAUGCACUGUUAAAGCACA  79.1％

2899  UCAGCGGAGUCAAGAAAAC  80.1％    2950  AAUGGAGAUGAGACGUUGC  79.1％

2900  CCGAUGAUUGUCGAACUUG  79.7％    2951  AAAUGCACUGUUAAAGCAC  79.0％

2901  GCAAGCAUGAGGAGGAAUU  79.7％    2952  ACUGUUAAAGCACAGAUUU  79.0％

2902  CAUGAUUGAAGCCGAGUCC  79.7％    2953  CCAAAUGCACUGUUAAAGC  79.0％

2903  CGAUGAUUGUCGAACUUGC  79.7％    2954  UGAAGACCCAAGUCACGAA  79.0％

2904  AUUGGCAAGCAUGAGAGGA  79.7％    2955  GCACUGUUAAAGCACAGAU  79.0％

2905  UUGCAAGCAUGAGGAGGAA  79.7％    2956  CAAAUGCACUGUUAAAGCA  79.0％

2906  CAAGCAUGAGGAGGAAUUA  79.7％    2957  CACUGUUAAAGCACAGAUU  79.0％

2907  GAUCCAAAUGCACUGUUAA  79.7％    2958  UUCAUCAAUGAACAAGGCG  78.9％

2908  CCAAGGGAGUGGAAGAAGG  79.6％    2959  UGCACUGUUAAAGCACAGA  78.9％

2909  ACAUUGCAAGCAUGAGGAG  79.6％    2960  UCAUCAAUGAACAAGGCGA  78.9％

2910  AUCCAAAUGCACUGUUAAA  79.6％    2961  AUGUUUCAUGUAUUCAGAU  78.9％

2911  CAUUGCAAGCAUGAGGAGG  79.6％    2962  UCCAAAUGCACUGUUAAAG  78.8％

2963    GGGAGGAAAUGGCCACAAA    78.8％    3014    CAAGUGCAGAAACUAAGAG    77.9％

2964    CAAAGGCAGACUACACUCU    78.8％    3015    UUGUUGUUCAGGCUCUUAG    77.8％

2965    GGGGAGGAAAUGGCCACAA    78.8％    3016    GGGAGAGACAGAACAAUGG    77.8％

2966    UAUGUUUCAUGUAUUCAGA    78.8％    3017    CAAACCACACGAAAAGGGA    77.8％

2967    GGAGGAAAUGGCCACAAAG    78.8％    3018    GGAUACAGAAUGAGUUCAA    77.8％

2968    GUAUGUUUCAUGUAUUCAG    78.8％    3019    UCACAUUUUCUCAUUCACU    77.8％

2969    ACUGGGGAGGAAAUGGCCA    78.7％    3020    UGGAUACAGAAUGAGUUCA    77.8％

2970    UUUCAUCAAUGAACAAGGC    78.7％    3021    GGAGAGACAGAACAAUGGC    77.8％

2971    GACAACACCAAGACCAAUC    78.7％    3022    GAACAAUGGCCUGGACAGU    77.7％

2972    CUGGGGAGGAAAUGGCCAC    78.7％    3023    CAAGCUGGAUACAGAAUGA    77.7％

2973    AGCAAUGGACGAUUUUCAA    78.7％    3024    UACAAAUGAGUUUCAAGAA    77.7％

2974    UGGGGAGGAAAUGGCCACA    78.7％    3025    AGCAUGAGGAGGAAUUAUU    77.6％

2975    AUGAUAAGCAAGUGCAGAA    78.7％    3026    AUACAGAAUGAGUUCAACA    77.6％

2976    AAUUAUUUCACAGCAGAGG    78.6％    3027    AGGGGAGAGACAGAACAAU    77.6％

2977    GUUAAAGCACAGAUUUGAA    78.6％    3028    GAGGGGAGAGACAGAACAA    77.6％

2978    AAAACAUGAAGAAAACGAG    78.6％    3029    GGGGAGAGACAGAACAAUG    77.6％

2979    AAAAACAUGAAGAAAACGA    78.6％    3030    GCAUGAGGAGGAAUUAUUU    77.6％

2980    ACAUGAAGAAAACGAGUCA    78.6％    3031    UCAAGCUGAUACAGAAAUG    77.6％

2981    AUUAUUUCACAGCAGAGGU    78.6％    3032    UUU3GUUCAGGCUCUUAGG    77.6％

2982    UCAAAAUGAAAUGGGGAAU    78.6％    3033    UUAUUUCACAGCAGAGGUG    77.6％

2983    AAACAUGAAGAAAACGAGU    78.6％    3034    GAUACAGAAUGAGUUCAAC    77.6％

2984    UGAUAAGCAAGUGCAGAAC    78.6％    3035    AUUCACAUUUUCUCAUUCA    77.6％

2985    AACAUGAAGAAAACGAGUC    78.6％    3036    ACAGCAGAGGUGUCCCAUU    77.6％

2986    CAAAAUGAAAUGGGGAAUG    78.5％    3037    CAGCAGGUGUGUCCCAUUG    77.6％

2987    AUGAUCCAAAUGCACUGUU    78.4％    3038    CACACAUUUCACAUUUCUC    77.6％

2988    AGGAAUUAUUUCACAGCAG    78.4％    3039    AAGCAUGAGAAGGAAUUAU    77.6％

2989    GAAUUAUUUCACAGCAGAG    78.4％    3040    CUGGAUACAGAAUGAGUUC    77.5％

2990    GGAAUUAUUUCACAGCAGA    78.4％    3041    CAUUCACAUUUUCUCAUUC    77.5％

2991    GAUGAUCCAAAUGCACUGU    78.3％    3042    ACACACAUUCACAUUUUCU    77.5％

2992    AAAGCAGGGCUAGGAUUAA    78.3％    3043    CAUGAGGAGGAAUUAUUUC    77.5％

2993    GUUGUUCAGGCUCUUAGGG    78.3％    3044    AGACCCAAGUCACGAAGGA    77.5％

2994    AUGAGGAGGAAUUAUUUCA    78.3％    3045    ACAUUCACAUUUUCUCAUU    77.5％

2995    UGAGGAGGAAUUAUUUCAC    78.3％    3046    CACAGCAGAGGUGUCCCAU    77.5％

2996    GAUAAGCAAGUGCAGAACU    78.1％    3047    ACACAUUCACAUUUUCUCA    77.5％

2997    UUAAAGAGAAAGACAUGAC    78.1％    3048    GCUGGAUACAGAAUGAGUU    77.5％

2998    GAAAGCGGGCUUAGGAUUA    78.1％    3049    ACCAAGACCAAUCAAACUU    77.5％

2999    UAAGCAAGUGCAGAACUAA    78.1％    3050    AAGCUGGAUACAGAAUGAG    77.5％

3000    UGAUCCAAAUGCACUGUUA    78.1％    3051    AGCUGGAUACAGAAUGAGU    77.5％

3001    UACAUUGCAAGCAUGAGGA    78.1％    3052    UUUCACAGCAGGAGUGUCC    77.5％

3002    AGCAAGUGCAGAACUAAAG    78.0％    30G3    CACAUUUACAUUUUCUCAU    77.5％

3003    UAAAGAGAAAGACAUGACC    78.0％    3054    CCAAGACCAAUCAAACUUC    77.5％

3004    GCAAGUGCAGAACUAAAGA    78.0％    3055    GAUCCCUGGGUUUUGCUCA    77.4％

3005    AUAAGCAAGUGCAGAACUA    78.0％    3056    CCUGGGGUUUGCUCAAUGC    77.4％

3006    AAGCAAGUGCAGAACUAAA    78.0％    3057    UGAUCCCUGGGUUUUGCUC    77.4％

3007    UUCACAUUUUCUCAUUCAC    77.9％    3058    CAUAAUGAAGGGGGUAUAC    77.4％

3008    AUUUCACAGCAGAGGUGUC    77.9％    3059    ACAUUAAUAAGGGGGUAUA    77.4％

3009    AAGUGCAGAACUAAAGAGG    77.9％    3060    CCCUGGGUUUUGCUCAAUG    77.4％

3010    AGUGCAGAACUAAAGAGGG    77.9％    3061    AUCCCUGGGUUUUGCUCAA    77A％

3011    GUGCAGAACUAAAGAGGGA    77.9％    3062    ACAGAAUGAGUUCAACAAG    77.4％

3012    CUUGUUGUUCAGGCUCUUA    77.9％    3063    CAAGACCAAUCAAACUUCC    77.4％

3013    UAUUUCACAGCAGAGUUGU    77.9％    3064    UACAUAAUGAAGGGGGUAU    77.4％

3065  UCCCUGGGUUUUGCUCAAU  77.4％    3116  UGGAGGUAUGUUUCAUGUA  76.2％

3066  AGAGACAGAACAAUGGCCU  77.3％    3117  CACAAAGGCAGACUACACU  76.2％

3067  AGACAGAACAAUGGCCUGG  77.3％    3118  AAUGGAAGAUUUUGUGCGA  76.1％

3068  ACAGACAAUGGCCUGGGAC  77.3％    3119  AGAGAAAGUAGACUUUGAC  76.1％

3069  UGAUUGUCGACUUGCAGA   77.3％    3120  GAAAGUAGACUUUGACAAC  76.1％

3070  GAGACAGAACAAUGGCCUG  77.3％    3121  AAUGGCCACAAAGGCAGAC  76.0％

3071  AUGAUUGUCGAACUUGCAG  77.3％    3122  GUCACUUUCAAGCUGGAUA  76.0％

3072  GACAGAACAAUGGCCUGGA  77.3％    3123  UUCAACCCGAUGAUUGUCG  75.9％

3073  UAAAAACAUGAAGAAAACG  77.1％    3124  UCAGGCUCUUAGGGACAAC  75.9％

3074  GAGAGACAGAACAAUGGCC  77.1％    3125  CAGGCUCUUAGGGACAACC  75.9％

3075  AAACAAUUGAAGAAAAAUU  77.0％    3126  CCAUUGGGAAAGUCUGUAG  75.9％

3076  AACAAUUGAAGAAAAAUUU  77.0％    3127  AGGCUCUUAGGGACAACCU  75.9％

3077  GAGGAGGAAUUAUUUCACA  76.9％    3128  UCAACCCGAUGAUUGUCGA  75.9％

3078  GAAACAAUUGAAGAAAAAU  76.9％    3129  UCCAUUGGGAAAGUCUGUA  75.8％

3079  GAGAAAGUAGACUUUGACA  76.9％    3130  ACAUAUAUUACCUUGAAAA  75.7％

3080  AGGAGGAAUUAUUUCACAG  76.9％    3131  GAUUGGGAAAUCUGUUAGG  75.7％

3081  GGAGGAAUUAUUUCACAGC  76.9％    3132  UUGGGAAAGUCUGUAGGAC  75.7％

3082  AGAACAAUGGCCUGGACAG  76.9％    3133  AUUGGGAAAGUCUGUAGGA  75.7％

3083  CAGAACAAUGGCCUGGACA  76.9％    3134  CACAUAUAUUACCUUGAAA  75.7％

3084  GAACCUGGGACCUUUGAUC  76.8％    3135  UCCACAUAUAUUACCUUGA  75.7％

3085  AUAUGAUGCGAUCAAGUGC  76.8％    3136  CCACAUAUAUUACCUUGAA  75.7％

3086  CUUUCAAGCUGGAUACAGA  76.8％    3137  UAGAACUUGAUGAUCCAAA  75.6％

3087  UAUGAUGCCAUCAAGUGCA  76.8％    3138  UUUGCAGCAAUAUGCACUC  75.6％

3088  AUGAUGCGAUCAAGUGCAU  76.8％    3139  UUGCAGCAAUAUGCACUCA  75.6％

3089  GAUUCAUCGAAAUUGGAGU  76.8％    3140  AUUUGCAGCAAUAUGCACU  75.6％

3090  AACCUGGGACCUUUGAUCU  76.8％    3141  AAGUCCACAUAUAUUACCU  75.6％

3091  AGAAACAAUUUGAAGAAAA  76.7％    3142  UUGUCGAACUUGCAGAAAA  75.6％

3092  AAGAAACAAUUGAAGAAAA  76.7％    3143  GAAGUCCACAUAUAUUACC  75.6％

3093  GAGGAAUUAUUUCACAGCA  76.7％    3144  GAACUUUGAUAUCCAAAUG  75.6％

3094  CACUUUCAAGCUGGAUACA  76.5％    3145  GUAGAACUUGAUGAUCCAA  75.5％

3095  UCACUUUCAAGCUGGAUAC  76.5％    3146  AACUUGAUGAUCCAAAUGC  75.5％

3096  GAUGAUUGUCGAACUUGCA  76.5％    3147  GGAAAUGGCCACAAAGGCA  75.5％

3097  AGAAAGUGACUUUUGACAA  76.4％    3148  GAUUGUCGAACUUGCAGAA  75.5％

3098  CCACAAAGGCAGACUACAC  76.3％    3149  AUUGUCGAACUUGCAGAAA  75.5％

3099  ACUUUCAAGCUGGAUACAG  76.3％    3150  AGAACUUGAUGAUCCAAAU  75.5％

3100  GAAAUGGCCACAAAGGCAG  76.3％    3151  ACUUGAUGAUCCAAAUGCA  75.4％

3101  AUGGCCACAAAGGCAGACU  76.3％    3152  AACAAUGGCCUGGACAGUA  75.4％

3102  GCCACAAAGGCAGACUACA  76.3％    3153  UGCAGCAAUAUGCACUCAC  75.4％

3103  AAAGUAGACUUUGACAACU  76.3％    3154  GUCCACAUAUAUUACCUUG  75.3％

3104  GAGGUAUGUUUCAUGUAUU  76.3％    3155  CAUCAAUGAACAAGGCGAA  75.3％

3105  ACAAAGGCAGACUACACUC  76.3％    3156  AGUCCACAUAUAUUACCUU  75.3％

3106  UGGGCCACAAAGCAGACUA  76.3％    3157  AGAUUCAUCGAAAUUGGAG  75.3％

3107  UUCAAGCUGGAUACAGAAU  76.3％    3158  AUCAUUGAACAGGGCGAAU  75.2％

3108  AGGUAUGUUUCAUGUAUUC  76.3％    3159  ACCAAUUUAUAUGGAUUCA  75.2％

3109  AAGUAGACUUUGACAACUG  76.2％    3160  CCAAUUUAUAUGGAUUCAU  75.2％

3110  AAAUGGCCACAAAGGCAGA  76.2％    3161  CAAUUUAUAUGGAUUCAUC  75.2％

3111  AAAUGGAAGAUUUUGUGCG  76.2％    3162  UCAAUGAACAAGGCGAAUC  75.2％

3112  UUUCAAGCUGGAUACAGAA  76.2％    3163  ACCCGAUGAUUGUCGAACU  75.1％

3113  GGAGGUAUGUUUCAUGUAU  76.2％    3164  AACCCGAUGAUUGUCGAAC  75.1％

3114  GGUAUGUUUCAUGUAUUCA  76.2％    3165  AAUGAACAAGGCGAAUCAA  75.1％

3115  GGCCACAAAGGCAGACUAC  76.2％    3166  CAACCCGAUGAUUGUCGAA  75.1％

3167   AUGAGCAAGGCGAAUCAAU  75.1％    3218  UGCAACACUACUGGAGCUG  74.1％

3168   AAAAUUGAACCUUUUCUGA  74.9％    3219  AUAUAUUACCUUGAAAAGG  74.1％

3169   CCCGAUGAUUGUCGAACUU  74.9％    3220  CCAGAUUUGUAUGAUUACA  74.1％

3170   UGAACAAGGCGAAUCAAUA  74.9％    3221  UAUUACCUUGAAAAGGCCA  74.1％

3171   CAAUGAACAAGGCGAAUCA  74.9％    3222  UUGGUGAAAACAUGGCACC  74.1％

3172   UUUUGAGAAUAAAUCAGAG  74.8％    3223  GUGAAAACAUGGCACCAGA  74.1％

3173   UUGAAACAAACAAAUUUGC  74.7％    3224  AUUUGUAUGAUUACAAGGA  74.1％

3174   AUUGAAACAAACAAAUUUG  74.7％    3225  GAAAAAUUUGAAAUCUCAG  74.1％

3175   AAAACCAAUUUAUAUGGAU  74.7％    3226  AAAAAUUUGAAAUCUCAGG  74.1％

3176   UUGAGAAUAAAUCAGAAGC  74.7％    3227  GGUGAAAACAUGGCACCAG  74.1％

3177   AAAUUGAAACAAACAAAUU  74.7％    3228  CAUAUAUUACCUUGAAAAG  74.1％

3178   UGGGAAAGUCUGUAGGACU  74.7％    3229  UAUUAUACCUUGAAAAGGC  74.1％

3179   AAACCAAUUUAUAUGGAUU  74.7％    3230  CAGAUUUGUAUGAUUACAA  74.1％

3180   AAAAUUGAAACAAACAAAU  74.7％    3231  GCUUCAACCCGAUGAUUGU  74.0％

3181   AACCAAUUUAUAUGGAUUC  74.6％    3232  ACAGUAUCUGCAACACUAC  74.0％

3182   UGAAACAAACAAAUUUGCA  74.6％    3233  AACUCCUUCCUGACACAUG  74.0％

3183   AAUUGAAACAAACAAAUUU  74.6％    3234  AACAGUAUCUGCAACACUA  74.0％

3184   UGGUUCAACUCCUUCCUGA  74.6％    3235  AGAUUUGUAUGAUUACAAG  74.0％

3185   AGCUCGAUGAAAUUGGAGA  74.5％    3236  UAUAUAGUCAAACCACACG  74.0％

3186   GAGCUCGAUGAAAUUGGAG  74.5％    3237  AUAUAGUCAAACCACACGA  74.0％

3187   AUCGAGAGCAUGAUUGAAG  74.5％    3238  AGCAUGGCCCAUUGGGGAG  74.0％

3188   UGGAUAGAGCUCGAUGAAA  74.5％    3239  GAAGAAAAAUUUGAAAUCU  74.0％

3189   GGAUAGAGCUCGAUGAAAU  74.5％    3240  UGGUGAAAACAUGGCACCA  74.0％

3190   AAUCAGAAGCAUGGCCCAU  74.4％    3241  CUGCAGAGACAUAAGCGAU  74.0％

3191   AAAUCAGAAGCAUGGCCCA  74.4％    3242  UGCUUCAACCCGAUGAUUG  74.0％

3192   UCAAAUGUCCAAAGAAGUG  74.4％    3243  AAGAAAAAUUUGAAAUCUC  74.0％

3193   UGCAGAGACUAAAGCGAUU  74.3％    3244  AGAAAAAUUUGAAAUCUCA  74.0％

3194   UUGUGAGCAUGGAGUUUUC  74.3％    3245  ACUCCUUCCUGACACAUGC  73.9％

3195   AUAGAGCUCGAUGAAAUUG  74.3％    3246  UUCAACUCCUUCCUGACAC  73.9％

3196   UCGAGAGCAUGAUUGAAGC  74.3％    3247  GUUCAACUCCUUCCUGACA  73.9％

3197   AAAGGCAGACUACACUCUC  74.3％    3248  GCAUGGCCCAUUGGGGAGU  73.9％

3198   AAAAACCAAUUUAUAUGGA  74.3％    3249  UGAAAACAUGGCACCAGAG  73.9％

3199   GCAGAGACAUAAGCGAUUU  74.3％    3250  GUAAACAGUAUCUGCAACA  73.9％

3200   UAGAGCUCGAUGAAAUUGG  74.3％    3251  AAAACAUGGCACCAGAGAA  73.9％

3201   UUUGUGAGCAUGGAGUUUU  74.3％    3252  CAACUCCUUCCUGACACAU  73.9％

3202   AGAGCUCGAUGAAAUUGGA  74.3％    3253  UCAACUCCUUCCUGACACA  73.9％

3203   GAUAGAGCUCGAUGAAAUU  74.3％    3254  GGUUCAACUCCUUCCUGAC  73.9％

3204   CUUGGUGAAAACAUGGCAC  74.2％    3255  GAAAACAUGGCACCAGAGA  73.9％

3205   CAGAGACAUAAGCGAUUUG  74.2％    3256  UUGGUUCAACUCCUUCCUG  73.8％

3206   CAGAAGCAUGGCCCAUUGG  74.2％    3257  UAAACAGUAUCUGCAACAC  73.8％

3207   AGGCAGACUACACUCUCGA  74.2％    3258  AAACAGUAUCUGCAACACU  73.8％

3208   UCAGAAGCAUGGCCCAUUG  74.2％    3259  GUGCGACAAUGCUUCAACC  73.8％

3209   GAAGCAUGGCCCAUUGGGG  74.2％    3260  CUUCAACCCGAUGAUUGUC  73.8％

3210   AAGGCAGACUACACUCUCG  74.2％    3261  CUCGACGAGGAAAGCAGGG  73.8％

3211   AAGCAUGGCCCAUUGGGGA  74.2％    3262  AAUUUGAAAUCUCAGGAAC  73.8％

3212   AAAAUUUGAAAUCUCAGGA  74.1％    3263  UCGACGAGGAAAGCAGGGC  73.8％

3213   AUAUUACCUUGAAAAGGCC  74.1％    3264  UGCGACAAUGCUUCAACCC  73.8％

3214   AUCAGAAGCAUGGCCCAUU  74.1％    3265  AAAUUUGAAAUCUCAGGAA  73.8％

3215   CUGGAUAGAGCUCGAUGAA  74.1％    3266  AAACAUGGCACCAGAGAAA  73.8％

3216   GAUUUGUAUGAUUACAAGG  74.1％    3267  CUCCUUCCUGACACAUGCA  73.8％

3217   AGAAGCAUGGCCCAUUGGG  74.1％    3268  CUCUCGACGAGGAAAGCAG  73.7％

3269  GCAGACUACACUCUCGACG  73.7％    3320  AUUACAAGGAGAACAGAUU  73.1％

3270  ACUCUCGACGAGGAAAGCA  73.7％    3321  GUUCAAUAGCCUGUAUGCA  73.1％

3271  UGUGCGACAAUGCUUCAAC  73.7％    3322  AAUAAAUCAGAAGCAUGGC  73.1％

3272  CAGACUACACUCUCGACGA  73.7％    3323  GAUUACAAGGAGAACAGAU  73.1％

3273  AACUGCAGAGACAUAAGCG  73.7％    3324  UAAAUCAGAAGCAUGGCCC  73.0％

3274  AUAGUCAAACCACACGAAA  73.7％    3325  AUUUAUAUGGAUUCAUCAU  73.0％

3275  ACUGCAGAGACAUAAGCGA  73.7％    3326  UAUAUGGAUUCAUCAUAAA  73.0％

3276  UAUAGUCAAACCACACGAA  73.6％    3327  GCGACAAUGCUUCAACCCG  73.0％

3277  CACUCUCGACGAGGAAAGC  73.6％    3328  AAUUUAUAUGGAUUCAUCA  73.0％

3278  GGCAGACUACACUCUCGAC  73.6％    3329  UUUAUAUGGAUUCAUCAUA  73.0％

3279  UACACUCUCGACGAGGAAA  73.6％    3330  UUAUAUGGAUUCAUCAUAA  73.0％

3280  ACACUCUCGACGAGGAAAG  73.6％    3331  CGACAAUGCUUCAACCCGA  73.0％

3281  ACAGAUUCAUCGAAAUUGG  73.6％    3332  UUACAAGGAGAACAGAUUC  73.0％

3282  UGGGCUCUUGGUGAAAACA  73.5％    3333  AUGAUUACAAGGAGAACAG  72.9％

3283  UGAAAUCUCAGGAACUAUG  73.5％    3334  UAUGAUUACAAGGAGAACA  72.9％

3284  UAGUCAAACCACACGAAAA  73.5％    3335  AGAAUAAAUCAGAAGCAUG  72.9％

3285  UCUUGGUGAAAACAUGGCA  73.5％    3336  CGAGAGCAUGAUUGAAGCC  72.9％

3286  AUUACCUUGAAAAGGCCAA  73.5％    3337  GAGAAUAAAUCAGAAGCAU  72.9％

3287  GAAAUCUCAGGAACUAUGC  73.5％    3338  GAAUAAAUCAGAAGCAUGG  72.9％

3288  UCUCGACGAGGAAAGCAGG  73.5％    3339  CUAAAGUGGGCUCUUGGUG  72.9％

3289  ACUGAGUACAUAAUGAAGG  73.5％    3340  UGAUUACAAGGAGAACAGA  72.9％

3290  AACAGAUUCAUCGAAAUUG  73.5％    3341  GCAACACUACUGGAGCUGA  72.8％

3291  UUUGAAAUCUCAGGAACUA  73.5％    3342  UGAGAAUAAAUCAGAAGCA  72.8％

3292  CUGAGUACAUAAUGAAGGG  73.5％    3343  AAAUUGAGCAUUGAAGACC  72.8％

3293  UUGAAAUCUCAGGAACUAU  73.5％    3344  AAAACAUUCUUUGGAUGGA  72.8％

3294  AUUUGAAAUCUCAGGAACU  73.5％    3345  CAACUAAAGUGGGCUCUUG  72.8％

3295  AUAAAUCAGAAGCAUGGCC  73.3％    3346  ACUAAAGUGGGCUCUUGGU  72.8％

3296  GGCUCUUGGUGAAAACAUG  73.3％    3347  GUAUGAUUACAAGGAGAAC  72.8％

3297  CUACACUCUCGACGAGGAA  73.3％    3348  AACUAAAGUGGGCUCUUGG  72.8％

3298  UUACCUUGAAAAGGCCAAU  73.3％    3349  AAUUGAGCAUUGAAGACCC  72.8％

3299  GGGCUCUUGGUGAAAACAU  73.3％    3350  AAACAUUCUUUGGAUGGAA  72.8％

3300  GACUACACUCUCGACGAGG  73.3％    3351  AUUGAGUACAUUGCAAGCA  72.7％

3301  ACUACACUCUCGACGAGGA  73.3％    3352  GUGGGCUCUUGGUGAAAAC  72.7％

3302  CUCUUGGUGAAAACAUGGC  73.3％    3353  UCAACUAAAGUGGGCUCUU  72.7％

3303  GCUCUUGGUGAAAACAUGG  73.3％    3354  AAUUGAGUACAUUGCAAGC  72.7％

3304  UGGUAGAACUUGAUGAUCC  73.3％    3355  GUCAACUAAAGUGGGCUCU  72.7％

3305  AUGAAGAAAACGAGUCAAC  73.2％    3356  AGUCAACUAAAGUGGGCUC  72.7％

3306  AGACUACACUCUCGAC3AG  73.2％    3357  CCAAUUGAGUACAUUGCAA  72.7％

3307  ACAAGGAGAACAGAUUCAU  73.2％    3358  CAAUUGAGUACAUUGCAAG  72.7％

3308  CAAUGCUUCAACCCGAUGA  73.2％    3359  UGUCAUGGAAGCAAGUAUU  72.6％

3309  GACAAUGCUUCAACCCGAU  73.2％    3360  AGUGGGCUUUUGGUGAAAA  72.6％

3310  ACAAUGCUUCAACCCGAUG  73.2％    3361  AAGUGGGCUCUUGGUGAAA  72.6％

3311  UGUUCAAUAGCCUGUAUGC  73.2％    3362  AGAACUAAAGAGGGAAGGC  72.6％

3312  AGUCAAACCACACGAAAAG  73.2％    3363  GAACUAAAGAGGGAAGGCG  72.6％

3313  UACAAGGAGAACAGAUUUA  73.2％    3364  CUGUCAUGGAAGCAAGUAU  72.5％

3314  GUGUUCAAUAGCCUGUAUG  73.2％    3365  UCGAUGAAAUUGGAGAGGA  72.5％

3315  AAUGCUUCAACCCGAUGAU  73.2％    3366  GCCUGCGAGCUAACUGAUU  72.5％

3316  GGUAGAACUUGAUGAUCCA  73.2％    3367  CUCGAUGAAAUUGGAGAGG  72.5％

3317  AUGCUUCAACCCGAUGAUU  73.2％    3368  UUGAGUACAUUGCAAGCAU  72.5％

3318  UGAAGAAAACGAGUCAACU  73.2％    3369  CCUGCGAGCUAACUGAUUC  72.5％

3319  UAAAGUGGGCUCUUGGUGA  73.1％    3370  CUGCGAGCUAACUGAUUCA  72.5％

3371  UUGAGCAUUGAAGACCCAA  72.4％    3422  GACAACUGCAGAGACAUAA  71.9％

3372  AGGAGAACAGAUUCAUCGA  72.4％    3423  UUCCUGACACAUGCAUUAA  71.9％

3373  CAAGGAGAACAGAUUCAUC  72.4％    3424  AGAACAGAUUCAUCGAAAU  71.9％

3374  CAGAUUCAUCGAAAUUGGA  72.4％    3425  ACUAAAGAGGGAAGGGCGA  71.9％

3375  AUUUGAAGGCCUAUGUUCU  72.4％    3426  GAAUGAGUUCAACAAGGCC  71.9％

3376  UUUCAAGGCCUAUGUUCUU  72.4％    3427  GACUUUGACAACUGCAGAG  71.7％

3377  AAGGAGAACAGAUUCAUCG  72.4％    3428  CUUUGACAACUGCAGAGAC  71.7％

3378  CCCCAAUUGAGUACAUUGC  72.3％    3429  AGGAAUGACACAGAUGUGG  71.7％

3379  UGAGUACAUUGCAAGCAUG  72.3％    3430  GAAUGACACAGAUGUGGUA  71.7％

3380  UGAGCAUUGAAGACCCAAG  72.3％    3431  CAACUGCAGAAACAUAAGC  71.7％

3381  ACUUUGUGAGCAUGGAGUU  72.3％    3432  GGAAUGACACAGAUGUGGU  71.7％

3382  GAGUACAUUGCAAGCAUGA  72.3％    3433  GAAGAAAACGAGUCAACUA  71.7％

3383  AUGACACAGAUGUGGUAAA  72.3％    3434  AAGAAAACGAGUCAACUAA  71.7％

3384  AAUGACACAGAUGUGGUAA  72.3％    3435  ACUUUGACAACUGCAGAGA  71.7％

3385  UUCAACAAGGCCUGCGAGC  72.3％    3436  AACGAGUCAACUAAAGUGG  71.6％

3386  GUCCAAAGAAGUGAAUGCC  72.3％    3437  UCCUGACACAUGCAUUAAA  71.6％

3387  UUCAAGGCCUAUGUUCUUG  72.3％    3438  CCAGGAAAGCAGGGCUAGG  71.6％

3388  UCAACAAGGCCUGCGAGCU  72.3％    3439  GGACAAACGGAACAUCAAA  71.6％

3389  AAACUUUGUGAGCAUGGAG  72.3％    3440  AGGACAAACGGAACAUCAA  71.6％

3390  AACUUUGUGAGCAUGGAGU  72.3％    3441  ACGAGUCAACUAAAGUGGG  71.6％

3391  GCCCCAAUUGAGUACAUUG  72.3％    3442  ACGAGGAAAGCAGGGCUAG  71.6％

3392  AGUACAUUGGAAGCAUGAG  72.3％    3443  ACACAUGCAUUAAAAUAGU  71.6％

3393  CCCAAUUGAGUACAUUGCA  72.3％    3444  CCUGACACAUGCAUUAAAA  71.6％

3394  UUUGUAUGAUUACAAGGAG  72.3％    3445  UGACACAUGCAUUAAAAUA  71 5％

3395  GGCCUGCGAGCUAACUGAU  72.2％    3446  GACAAACGGAACAUCAAAG  71.5％

3396  AAGGCCUGCGAGCUAACUG  72.2％    3447  UAGUAAACAGUAUCUGCAA  71.5％

3397  AUUGAGCAUUGAAGACCCA  72.2％    3448  GUAGUAAACAGUAUCUGCA  71.5％

3398  GAGUUCAACAAGGCCUGCG  72.2％    3449  AACUAAAGAGGGAAGGCGA  71.5％

3399  GAGCAUUGAAGACCCAAGU  72.2％    3450  AGAAAACGAGUCAACUAAA  71.5％

3400  UUGACAACUGCAGAGACAU  72.2％    3451  GACGAGGAAAGCAGGGCUA  71.5％

3401  GUUCAACAAGGCCUGCGAG  72.2％    3452  CACAUGCAUUAAAAUAGUU  71.5％

3402  AGUUCAACAAGGCCUGCGA  72.2％    3453  AAAACGAGUCAACUAAAGU  71.4％

3403  UUUGACAACUGCAGAGACA  72.2％    3454  UAAGGAAUGACACAGAUGU  71.4％

3404  GCUGGAUGAAAUUGGAGAG  72.2％    3455  CCACUGAGUACAUAAUGAA  71.4％

3405  AGGCCUGCGAGCUAACUGA  72.2％    3456  CGAGUCAACUAAAGUGGGC  71.4％

3406  UGAGUUCAACAAGGCCUGC  72.2％    3457  AAACGAGUCAACUAAAGUG  71.4％

3407  UCCUUCCUGACACAUGCAU  72.1％    3458  CUGACACAUGCAUUAAAAU  71.4％

3408  AUGAGUUCAACAAGGCCUG  72.1％    3459  GCCACUGAGUACAUAAUGA  71.4％

3409  AAUGAGUUCAACAAGGCCU  72.1％    3460  GUACAUUGCAAGCAUGAGG  71.4％

3410  CCUUCCUGACACAUGCAUU  72.1％    3461  CUUUGUGAGCAUGGAGUUU  71.3％

3411  AACAAGGCCGCUGAGCUAA  72.0％    3462  UGAGGACAAACGGAACAUC  71.3％

3412  CUUCCUGACACAUGCAUUA  72.0％    3463  GAGGACAAACGGAACAUCA  71.3％

3413  CAAGGCCUGCGAGCUAACU  72.0％    3464  AAGGAAUGAGACCAGUGUG  71.3％

3414  GGAGAACAGAUUCAUCGAA  72.0％    3465  UUAAGGAAUGACACAGAUG  71.3％

3415  CAACAAGGCCUGCGAGCUA  72.0％    3466  AGUAAACAGUAUCUGCAAC  71.3％

3416  ACAAGGCCUGCGAGCUAAC  72.0％    3467  CAUGAAGAAAACGAGUCAA  71.2％

3417  ACAACUGCAGAGACAUAAG  71.9％    3468  CACUGAGUACAUSAUGAAG  71.2％

3418  GAGAACAGAUUCAUCGAAA  71.9％    3469  CAGUAGUAAACAGUAUCUG  71.2％

3419  GAACAGAUUCAUCGAAAUU  71.9％    3470  GACAGUAGUAAACAGUAUC  71.2％

3420  UGACAACUGCAGAGACAUA  71.9％    3471  AGUAGUAAACAGUAUCUGC  71.2％

3421  CUAAAGAGGGAAGGCGAAA  71.9％    3472  CAAUGGACGAUUUUCAACU  71.2％

3473    ACAGUAGUAAACAGUAUCU    71.2％    3505    AUUCAUCGAAAUUGGAGUG    70.7％

3474    GCAAUGGACGAUUUUCAAC    71.2％    3506    UCAUCGAAAUUGGAGUGAC    70.7％

3475    GACACAUGCAUUAAAAUAG    71.1％    3507    CAAGUCACGAAGGAGAAGG    70.6％

3476    GUCAUGGAAGCAAGUAUUG    71.1％    3508    UCAUCAUAAAAGGAAGAUC    70.6％

3477    AAAGUGGGCUCCUUUGGAA    71.1％    3509    UGGACGADUUCUAACUAAU    70.6％

3478    UAUGUGAGGACAAACGGAA    71.0％    3510    UCCAAAUUCUCCCUGAUGG    70.6％

3479    GUGAGGACAAACGGAACAU    71.0％    3511    AGUCACGAAGGAGAAGGGA    70.6％

3480    UCCUCCUGAUGGAUGCUUU    71.0％    3512    CAAAUUCCUCCUGAUGGAU    70.6％

3481    CGACGAGGAAGCGAGGGCU    71.0％    3513    CCAAAUUCCUCCUGAUGGA    70.6％

3482    UUCCUCCUGAUGGAUGCUU    71.0％    3514    AAUGGACGAUUUUCAACUA    70.6％

3483    UGUGAGGACAAACGGAACA    71.0％    3515    CCAAGUCACGAAGGAGAAG    70.6％

3484    AUGUGAGGACAAACGGAAC    71.0％    3516    AUGGACGAUUUUCAACUAA    70.6％

3485    UUGUAUGUGAGGACAAACG    70.9％    3517    AAUUCCUCCUGAUGGAUGC    70.6％

3486    UGUAUGUGAGGACAAACGG    70.9％    3518    UUCAUCAUAAAAGGAAGAU    70.6％

3487    GUGUAGGAGGACAAAGGGA    70.9％    3519    GUCACGAAGGAGAAGGGAU    70.6％

3488    AGUAUCUGCAACACUACUG    70.8％    3520    AAAUUCCUCCUGAUGGAUG    70.6％

3489    GAGCCACUGAGUACAUAAU    70.8％    3521    CAUUGGAAGCAAGUAUUUC    70.6％

3490    AGCCACUGAGAGUAUAAUG    70.8％    3522    AUGGAAGCAAGUAUUGUCA    70.6％

3491    AGAGCCCUGAGUGUCAUAA    70.8％    3523    GGAAAGCAGGGGCUAGAAU    70.6％

3492    CAGUAUCUGCAACACUACU    70.8％    3524    AAAAUCUCAGGAACAUGCG    70.5％

3493    GUAUCUGCAACACUACUGG    70.8％    3525    CCCAAGUCACGAAGGAGAA    70.5％

3494    GAAAACGAGUCAACUAAAG    70.7％    3526    GAUUGAAGCCGAGUCCUCG    70.4％

3495    UUCAUCGAAAUUGGAGUGA    70.7％    3527    CGAUGAAAUUGGAGAGGAC    70.1％

3496    AGACUUUGACAACUGCAGA    70.7％    3528    AUUCCUCCUGAUGGAUGCU    70.1％

3497    AGUAGACUUUGACAACUGC    70.7％    3529    GUCCAAAUUCCUCCUGAUG    70.1％

3498    GGAAGCAAGUAUUGUCAGA    70.7％    3530    GGUCCAAAUUCCUCCUGAU    70.1％

3499    UAGACUUUGACAACUGCAG    70.7％    3531    UGAGCAUGGAGUUUUCUCU    70.0％

3500    GUAGACUUUGAUAACUGCA    70.7％    3532    UCAUAAAAGGAAGAUCUCA    70.0％

3501    UGGAAGCAAGUAUUGUCAG    70.7％    3533    AAGAAGUGCCAUAGGCCAA    70.0％

3502    CUUGUAUGUGAGGACAAAC    70.7％    3534    CGGUCCAAAUUCCUCCUGA    70.0％

3503    CAUCGAAAUUGGAGUGACA    70.7％    3535    AUCAUAAAAGGAAGAUCUC    70.0％

3504    UCAUGGAGCAAGUGUAUGU    70.7％    3536    UGUGAGCAUGGAGUUUUCU    70.0％

表2-4在表1-4所列甲型流感片段2(HA)序列中以至少70％存在的保守19-mer序列

Seq

ID   序列                   百分比

3537 GCAUCACUCCAAAUGGAAG    70.4％

3538 UGCAUCACUCCAAAUGGAA    70.4％

3539 AUGCAUCACUCCAAAUGGA    70.4％

3540 AAUGCAUCACUCCAAAUGG    70.3％

3541 GAAUGCAUCACUCCAAAUG    70.3％

3542 UCACUCCAAAUGGAAGCAU    70.3％

3543 UGUUACCCUUAUGAUGUGC    70.2％

3544 CAUCACUCCAAAUGGAAGC    70.2％

3545 AUCACUCCAAAUGGAAGCA    70.2％

表2-5在表1-5所列甲型流感片段2(NP)序列中以至少70％存在的保守

19-mer序列

ID     序列    百分比                   3596   GAAAUGCUGAGAUCGAAGA    91.2％

                                        3597   GAACCCAGGAAAUGCUGAG    91.2％

3546   UCUUAUUCUUCGGAGACA     98.0％    3598   CCAGGAAAUGCUGAGAUCG    91.1％

3547   AUUUCUUCGGAGACAAUGC    97.9％    3599   AGGAAUGCUUGAGAUCGAA    91.1％

3548   UAUUUCUUCGGAGACAAUG    97.9％    3600   CAGGAAUGCUUGAGAUCGA    91.1％

3549   UUAUUUCUUCGGAGACAAU    97.9％    3601   GGAAAUGCUGAGAUCGAAG    91.1％

3550   CUUAUUUCUUCGGAGACAA    97.9％    3602   UGGAUCAAGUGAGAGAAAG    90.7％

3551   UUUCUUCGGAGACAAUGCA    97.8％    3603   UAUGAGAAUGUGUGCAACA    90.4％

3552   AUGAAGGAUCUUAUUUCUU    97.6％    3604   AUGAGAGAAUGUGCAACAU    90.4％

3553   AAUGAAGGAUCUUAUUUCU    97.6％    3605   GAAAAUUUCAAACAGCUGC    90.1％

3554   GAAGGAUCUUAUUUCUUCG    97.5％    3606   GGAAAAUUUUCAACAGCUG    90.1％

3555   AAGGAUCUUAUUUCUUCGG    97.5％    3607   AAAGGAAAAUUUCAAACAG    90.0％

3556   UGAAGGAUCUUAUUUCUUC    97.4％    3608   AGGAAAAUUUCAAACAGCU    90.0％

3557   UAAUGAAGGAUCUUAUUUC    97.3％    3609   AAGGAAAAUUUCAAACAGC    90.0％

3558   UUCUUCGGAGACAAUGCAG    96.5％    3610   CCCAGGAAAUGCUGAGAUC    90.0％

3559   UCUUCGGAGACAAUGCAGA    96.4％    3611   AAAAUUUCAAACAGCUGCA    89.7％

3560   GAUCUUAUUUCUUACGGAA    96.0％    3612   CUUAUGAACAGAUGGAAAC    89.5％

3561   GGAUCUUAUUUCUUCGGAG    96.0％    3613   UCUUAUGAACAGAUGGAAA    89.5％

3562   AUCUUAUUUCUUCGGAGAC    96.0％    3614   UAUGAACAGAUGGAAACUG    89.5％

3563   AGGAUCUUAUUUCUUCGGA    95.8％    3615   AGGGAACUCGUCCUUUAUG    89.5％

3564   AGUAAUGAAGGAUCUUAUU    95.4％    3516   GGGAACUCGUCCUUUAUGA    89.5％

3565   GUUAAUGAAGAUCUAUUUU    95.4％    3617   UUAUGAACAGAUGGAAACU    89.1％

3566   AUGAGUAAUGAAGGAUCUU    95.3％    3618   AUUCUGCUGCAUUUGAAGA    89.0％

3567   UGAGUAAUGAAGGAUCUUA    95.3％    3619   UGAGGGAACUCGUCCUUUA    88.8％

3568   GAGUAUUGAAGGAUCUUAU    95.3％    3620   GAGGGAACUCGUCCUUUAU    88.7％

3569   UACAAAUUGCUUCAAAUGA    93.7％    3621   UUCUGCUGCAUUUGAAGAU    88.6％

3570   AAUUUCAAACAGCUGCACA    93.5％    3622   GAGGAAACACUAAUCAACA    88.2％

3571   AAAUUUCAAACAGCUGCAC    93.5％    3623   GGAGGAAACACUAAUCAAC    88.2％

3572   GUACAAAUUGCUUCAAAUG    93.4％    3624   AGUGGAGGAAACACUAAUC    88.2％

3573   AUGGUGCUCUCUGCUUUUG    93.3％    3625   GUGGAGGAAACACUAAUCA    88.1％

3574   UGGUGCUCUCUGCUUUUGA    93.3％    3626   UGGAGGAAACACUAAUCAA    88.1％

3575   CAAGGCACCAAACGGUCUU    93.2％    3627   GAGGGUCGUUGCUACACAA    87.8％

3576   AAGGCACCAAACGGUCUUA    93.2％    3628   AGAGGGUCAGUUGCUCACA    87.8％

3577   AGAGAAUGUGCAACAUUCU    93.0％    3629   CAGCUGGUGUGGAUGGCAU    87.6％

3578   GAGAGAAUGUGCAACAUUC    93.0％    3630   AGCUGGUGUGGAUGGCAUG    87.6％

3579   AUUUCAAACAGCUGCACAA    92.7％    3631   GCUGGUGUGGAUGGCAUGC    87.5％

3580   UUUCAAACAGCUGCACAAA    92.7％    3632   ACUUCGAAAAAGAGGGAUA    87.4％

3581   GGAACCCAGGAAAUGCUGA    92.2％    3633   CAACGAACCCGAUCGUGCC    87.2％

3582   CGAACCCGAUCGUGCCCUC    92.1％    3634   GCAACGAACCCGAUCGUGC    87.2％

3583   CGGAACCCAGGAAAUGCUG    92.1％    3635   AUGAGGGCAGAAAUCAUAA    87.2％

3584   AAUGCUGAGAUCGAAGAUC    91.7％    3636   UCAGCUGGUGUGGAUGGCA    87.1％

3585   AUGCUGAGAUCGAAGAUCU    91.7％    3637   GUCAGCUGGUGUGGAUGGC    87.1％

3586   GAUUCUACAUCCAAAUGUG    91.6％    3638   GGCAACGAACCCGAUCGUG    87.1％

3587   GCUGAGAUCGAAGAUCUCA    91.5％    3639   AGUCAGCUGGUGUGGAUGG    87.1％

3588   UCAUGGCAGCAUUCACUGG    91.5％    3640   UUAAACAAGCUGCACAAAG    87.0％

3589   AAUGGUGCUCUCUGCUUUU    91.5％    3641   UUCUACAUCCAAAUGUGCA    86.9％

3590   ACCCAGGAAAUGCUGAGAU    91.4％    3642   UCUACAUCCAAAUGUGCAC    86.9％

3591   UCAGACAUGAGGGCAGAAA    91.4％    3643   CAUGAGGGCAGAAAUCAUA    86.8％

3592   UGCUGAGAUCGAAGAUCUC    91.4％    3644   ACAUGAGGGCAGAAAUCAU    86.8％

3593   CAGACAUGAGGGCAGAAAU    91.4％    3645   GACAUGAGGGCAGAAAUCA    86.8％

3594   AACCCAGGAAAUGCUGAGA    91.4％    3646   GAGUACAAAUUGCUUCAAA    86.7％

3595   AAAUGCUGAGAUCGAAGAU    91.2％    3647   GCACACAAGAGUCAGCUGG    86.7％

3648   GAGAAUCCAGCACACAAGA    86.7％    3702   CGAGAAUCCAGCACACAAG    85.1％

3649   CACACAAGAGUCAGCUGGU    86.7％    3703   AACACUAAUCAACAGAGGG    85.1％

3650   GGAGUACAAAUUGCUUCAA    86.7％    3704   AGGAAACACUAAUCAACAG    85.1％

3651   AGAAUCCAGCACACAAGAG    86.7％    3705   GAAACACUAAUCAACAGAG    85.0％

3652   CAGCACACAAGAGUCAGCU    86.6％    3706   AGGAGUACAAAUUGCUUCA    85.0％

3653   AGUACAAAUUGCUUCAAAU    86.6％    3707   GAGGAGACAUAAUUGCUUC    85.0％

3654   CCAGCACACAAGAGUCAGC    86.6％    3708   AGAGGAGUACAAAUUGCUU    85.0％

3655   AUUCUACAUCCAAAUGUGC    86.6％    3709   AAACACUAAUCAACAGAGG    85.0％

3656   ACAAGAGUCAGCUGGUGUG    86.5％    3710   UAUUGAGAGGGUCAGUUGC    84.9％

3657   AGCACACAAGAGUCAGCUG    86.5％    3711   AACCCGAUCGUGCCCUCUU    84.6％

3658   UGCUUAUGAGAGAAUGUGC    86.5％    3712   CCCGAUCGUGCCCUCUUUU    84.6％

3659   CAAGAGUCAGCUGGUGUGG    86.5％    3713   GAACCCGAUCGUGCCCUCU    84.6％

3660   AGAGUCAGCUGGUGUGGAU    86.5％    3714   ACCCGAUCGUGCCCUCUUU    84.6％

3661   GAGUCAGCUGGUGUGGAUG    86.5％    3715   CGAUCGUGCCCUCUUUUGA    84.5％

3662   CACAAGAGUCAGCUGGUGU    86.5％    3716   CCGAUCGUGCCCUCUUUUG    84.5％

3663   GCUUAUGAGAGAAUGUGCA    86.5％    3717   CUAGAGGAGUACAAAUUGC    84.2％

3664   CUUAUGAGAGAAUGUGCAA    86.5％    3718   ACUAGAGGAGUACAAAUUG    84.1％

3665   AAGAGUCAGCUGGUGUGGA    86.5％    3719   UAGAGGAGUACAAAUUGCU    84.1％

3666   CCAAACGGUCUUAUGAACA    86.4％    3720   AGAUGGAAACUGAUGGGGA    84.0％

3667   GGCACCAAACGGUCUUAUG    86.4％    3721   CAGAUGGAAACUGAUGGGG    84.0％

3668   GCACCAAACGGUCUUAUGA    86.4％    3722   AGUGGGUACGACUUCGAAA    84.0％

3669   ACCAAACGGUCUUAUGAAC    86.4％    3723   ACAGAUGGAAACUGAUGGG    84.0％

3670   AGGCACCAAACGGUCUUAU    86.4％    3724   CUAAUCAACAGAGGGCCUC    84.0％

3671   UGAGAGAAUGUGCAACAUU    86.4％    3725   ACUAAUCAACAGAGGGCCU    84.0％

3672   AAUCCAGCACACAAGAGUC    86.3％    3726   CAGUGGGUACGACUUCGAA    83.9％

3673   ACACAAGAGUCAGCUGGUG    86.3％    3727   CCAGUGGGUACGACUUCGA    83.9％

3674   AUCCAGCACACAAGAGUCA    86.3％    3728   UGAUGGAAGGUGCAAAACC    83.8％

3675   CACCAAACGGUCUUAUGAA    86.3％    3729   AAGAAGAAAUAAGGCGAAU    83.8％

3676   AGACAUGAGGGCAGAAAUC    86.2％    3730   GUGGGUACGACUUCGAAAA    83.8％

3677   GACUUCGAAAAAGAGGGAU    86.2％    3731   AAAGAAGAAAUAAGGCGAA    83.8％

3678   GAAUCCAGCACACAAGAGU    86.2％    3732   GAUGGAAGGUGCAAAACCA    83.7％

3679   CAGAGGACAAGAGCUCUUG    86.1％    3733   UGUGCUCUCUGAUGCAGGG    83.7％

3680   CGGUCUUAUGAACAGAUGG    86.1％    3734   AUAUUGAGAGGGUCAGUUG    83.7％

3681   AGAGGACAAGAGCUCUUGU    86.1％    3735   AUGUGCUCUCUGAUGCAGG    83.7％

3682   ACGGUCUUAUGAACAGAUG    86.1％    3736   AUGGUAGGUGCAAAACCAG    83.7％

3683   UACGACUUCGAAAAAGAGG    86.1％    3737   UGGAAGGUGCAAAACCAGA    83.7％

3684   GGUCUUAUGAACAGAUGGA    86.1％    3738   CACUAAUCAACAGAGGGCC    83.6％

3685   ACGACUUCGAAAAAGAGGG    86.1％    3739   AUGAUGGAAGGUGCAAAAC    83.6％

3686   AACGGUCUUAUGAACAGAU    86.0％    3740   ACCAGAGGACAAGAGCUCU    83.5％

3687   AAACGGUCUUAUGAACAGA    86.0％    3741   UACCAGAGGACAAGAGCUC    83.5％

3688   CAACGGUCUUUAUGAACAG    86.0％    3742   AGAUGAUUGAUGGAAUUGG    83.2％

3689   UUAUGAGAGAAUGUGCAAC    86.0％    3743   CCAGAGGACAAGAGCUCUU    83.2％

3690   CGACUUCGAAAAAGAGGGA    85.8％    3744   AAGAUGAUUGAUGGAAUUG    83.2％

3691   UCCAGCACACAAGAGUCAG    85.7％    3745   GAAAUAAGGCGAAUCUGGC    83.0％

3692   AUGAACAGAUGGAAACUGA    85.7％    3746   AAAUAAGGCGAAUCUGGCG    83.0％

3693   UGAACAGAUGGAAACUGAU    85.6％    3747   GAGAGGGUCAGUUGCUCAC    83.0％

3694   AACAGAUGGAAACUGAUGG    85.6％    3748   UGAGAGGUCAGGUUGCUGA    83.0％

3695   GUCUUUAUGAACAGAUGAA    85.6％    3749   CUGAACUUAAACUCAGUGA    82.9％

3696   CUGAGAUCGAAGAUCUCAU    85.6％    3750   UGAACUUAAACUCAGUGAU    82.9％

3697   GAACAGAUGGUAACUGAUG    85.6％    3751   UUGAGAGGGUCAGUUGCUC    82.9％

3698   GGAAACACUAAUCAACAGA    85.5％    3752   ACUGACUUAAACUCAGUUG    82.9％

3699   ACGAGAAUCCAGCACACAA    85.4％    3753   CAAACAGCUGCACAAAGAG    82.8％

3700   AACGAGAAUCCAGCACACA    85.4％    3754   AUUGGAGAGGGUCAGUUCU    82.8％

3701   ACACUAAUCAACAGAGGGC    85.1％    3755   AAACAGCUGCACAAAGAGC    82.8％

3756  UCAGUUGCUCACAAAUCUU    82.8％    3810  AGGACAAGAGCUCUUGUUC    79.1％

3757  UGGGUACGACUUCGAAAAA    82.7％    3811  UCUGGAGAGGUGAGAAUGG    78.9％

3758  CAGUUGCUCACAAAUCUUG    82.7％    3812  UUCUGGAGAGGUGAGAAUG    78.9％

3759  GGGUACGACUUCGAAAAAG    82.7％    3813  CCCAGCGCGGGGAAAGAUC    78.9％

3760  GGUACGACUUCGAAAAAGA    82.7％    3814  CCAGCGCGGGGAAAGAUCC    78.9％

3761  UCAAACAGCUGCACAAAGA    82.7％    3815  UACUGGGCCAUAAGGACCA    78.8％

3762  GUACGACUUCGAAAAAGAG    82.6％    3816  ACUGGGCCAUAAGGACCAG    78.7％

3763  GAUGAGGGAACUCGUCCUU    82.5％    3817  GAGGACAAGAGCUCUUGUU    78.3％

3764  UGGAUGAGGGAACUCGUCC    82.5％    3818  AUGGCGUCCCAAGGCACCA    77.8％

3765  GGAUGAGGGAACUCGUCCU    82.5％    3819  UGGCGUCCCAGGCAACCAA    77.7％

3766  CAGCUGCACAAAGAGCAAU    82.5％    3820  CGUCCCAAGGCACCAAACG    77.7％

3767  AUGAGGGAACUCGUCCUUU    82.5％    3821  GGCGUCCCAAGGCACCAAA    77.7％

3768  AGCUGCACAAAGAGCAAUG    82.5％    3822  GCGUCCCAAGGCACCAAAC    77.7％

3769  ACAGCUGCACAAAGAGCAA    82.4％    3823  UGUGCACUGAACUUAAACU    77.4％

3770  AACAGCUGCACAAAGAGCA    82.4％    3824  GUGCAACUGAACUUAACUC    77.4％

3771  UAAGCUUCAUCAGAGGGAC    82.2％    3825  AUGUGCACUGAACUUAAAC    77.4％

3772  AGAAAUAAGGCGAAUCUGG    82.2％    3826  CCAAGGCACCAAACGGUCU    77.4％

3773  GAAGAAAUAAGGCGAAUCU    82.1％    3827  CACUGAACUUAAACUCAGU    77.3％

3774  AAGAAAUAAGGCGAAUCUG    82.1％    3828  UGCACUGAACUUAAACUCA    77.3％

3775  UUAAGCUUCAUCAGAGGGA    82.1％    3829  GCAUGAACCUUAAACUCAG    77.3％

3776  GGGAAGAUGAUUGAUGGAA    82.1％    3830  CCCAAGGCACCAAACGGUC    77.2％

3777  ACGAACCCGAUCGUGCCCU    82.1％    3831  UCCCAAGGCACCAAACGGU    77.1％

3778  GUAAGAUGAUUGUUGGAAU    82.1％    3832  AGAUCGAAGAUCUCAUAUU    76.9％

3779  AACGAACCCGAUCGUGCCC    82.1％    3833  GAGAUCGAAGAUCUCAUAU    76.9％

3780  GCCAGAAUGCAACUGAGAU    82.1％    3834  UGAGAUCGAAGAUCUCAUA    76.9％

3781  AGAAGAAAUUAGGCGAAUC    82.1％    3835  GUCCCAAGGCACCAAACGG    76.9％

3782  CGCCAGAAUGCAACUGAGA    82.1％    3836  GUACUGGGCCAUAAGGACC    76.8％

3783  GUGCUCUCUGCUUUUGAUG    81.7％    3837  UGGUGUGGAUGGCAUGCCA    76.6％

3784  GGUGCUCUCUGCUUUUGAU    81.7％    3838  GUGCUUAUGAGAGAAUGUG    76.4％

3785  UGCUCUCUGCUUUUGAUGA    81.7％    3839  GGUACUGGGCCAUAAGGAC    76.3％

3786  GAAGAUGAUUGAUGGAAUU    81.6％    3840  GUGUGGAUGGCAUGCCAUU    76.1％

3787  AUCCGUCGGGAAGAUGAUU    81.5％    3841  UGUGGAUGGCAUGCCAUUC    76.1％

3788  CAUCCGUCGGGAAGAUGAU    81.5％    3842  GGUGUGGAUGGCAUGCCAU    76.1％

3789  UCGGGAAGAUGAUUGAUGG    81.4％    3843  CAUACCAGAGGACAAGAGC    76.1％

3790  CGGGAAGAUGAUUGAUGGA    81.4％    3844  CAACAUACCAGAGGACAAG    76.1％

3791  AAGGCAACGAACCCGAUCG    81.3％    3845  ACAUACCAGAGGACAAGAG    76.1％

3792  AGGCAACGAACCCGAUCGU    81.3％    3846  CUGGUGUGGAUGGCAUGCC    76.0％

3793  GGUCAGUUGCUCACAAAUC    81.2％    3847  AACAUACCAGAGGACAAGA    75.9％

3794  GGGUCAGUUGCUCACAAAU    81.2％    3848  AUACCAGAGGACAAGAGCU    75.9％

3795  GUCGGGAAGAUGAUUGAUG    81.1％    3849  ACAUCCAAAUGUGCACUGA    75.8％

3796  AGGGUCAGUUGCUCACAAA    81.1％    3850  UACAUCCAAAUGUGCACUG    75.8％

3797  UCCGUCGGGAAGAUGAUUG    81.1％    3851  CUACAUCCAAAUGUGCACU    75.8％

3798  AAAGAAACCUCCCAUUUGA    81.0％    3852  GAUCGAAGAUCUCAUAUUU    75.8％

3799  CGUCGGGAAGAUGAUUGAU    81.0％    3853  AUCCAAAUGUGCACUGAAC    75.4％

3800  CAAAGAAACCUCCCAUUUG    81.0％    3854  CCUUUCAAACUACUUCAAA    75.4％

3801  CCGUCGGGAAGAUGAUUGA    81.0％    3855  UCCAAAUGUGCACUGAACU    75.4％

3802  UGAGGGCAGAAAUCAUAAG    80.7％    3856  CAUCCAAAUGUGCACUGAA    75.4％

3803  GGAAUAGACCCUUUCAAAC    80.6％    3857  CAAAUGUGCACUGAACUUA    75.3％

3804  GAAUAGACCCUUUCAAACU    80.6％    3858  AAAUGUGCACUGAACUUAA    75.3％

3805  GUGGGAAUAGACCCUUUCA    80.5％    3859  CUUUCAAACUACUUCAAAA    75.2％

3806  UGGGAAUAGACCCUUUCAA    80.5％    3860  AAUGUGCACUGAACUUAAA    75.1％

3807  GUCAGUUGCUCAUAAAUCU    80.4％    3851  UACUCUUGAACUGAGAAGC    75.1％

3808  GGGAAUAGACCCUUUCAAA    80.3％    3862  GUGACAUCAAAAUCAUGGC    75.1％

3809  GGACAAGAGCUCUUGUUCG    79.1％    3863  UGACAUCAAAAUCAUGGCG    75.0％

3864  ACAUCAAAAUCAUGGCGUC    74.9％    3918  AGGAGUGGAGGAAACACUA    72.3％

3855  GACAUCAAAAUCAUGGCGU    74.9％    3919  GAGUGGAGGAAACACUAAU    72.3％

3866  CCAGGAGUGGAGGAAACAC    74.9％    3920  GGAGUGGAGGAAACACUAA    72.3％

3867  ACCAGGAGUGGAGGAAACA    74.9％    3921  CAGGAGUGGAGGAAACACU    72.2％

3868  AGUGACAUCAAAAUCAUGG    74.9％    3922  UCAAACGGGGGAUCAACGA    72.0％

3869  GACCCUUUCAAACUACUUC    74.8％    3923  CAAACGGGGGAUCAACGAU    71.9％

3870  GUACUCUUGAACUGAGAAG    74.8％    3924  CUUAAACUCAGUGAUUAUG    71.9％

3871  ACCCUUUCAAACUACUUCA    74.8％    3925  AGAAUGCAACUGAGAUUAG    71.9％

3872  AGUACUCUUGAACUGAGAA    74.7％    3926  CAGAAUGCAACUGAGAUUA    71.9％

3873  GAGUGACAUCAAAAUCAUG    74.6％    3927  UUAAACUCAGUGAUUAUGA    71.9％

3874  CCCUUUCAAACUACUUCAA    74.6％    3928  AAACGGGGGAUCAACGAUC    71.7％

3875  CCAAAUGUGCACUGAACUU    74.5％    3929  AACGGGGGAUCAACGAUCG    71.7％

3876  AGUGCUUAUUGAGAAUGGU    74.4％    3930  UCAAAUGAGAACAUGGAUA    71.6％

3877  GGAUGGCAUGCCAUUCUGC    74.3％    3931  GUUAAGCUUCAUCAGAGGG    71.6％

3878  UGGAUGGCAUGCCAUUCUG    74.2％    3932  UUCAAAUGAGAACAUGGAU    71.6％

3879  CUUCAAAUGAGAACAUGGA    74.1％    3933  CUCACAUGAUGAUCUGGCA    71.5％

3880  CAAAUUGCUUCAAAUGAGA    74.1％    3934  GAAGGUGCAAAACCAGAAG    71.5％

3881  GCUUCAAAUGAGAACAUGG    74.1％    3935  CUUCGGAGACAAUGCAGAA    71.5％

3882  AAAUUGCUUCAAAUGAGAA    74.0％    3936  GGAAGGUGCAAAACCAGAA    71.5％

3883  AUUGCUUCAAAUGAGAACA    74.0％    3937  AAGGUGCAAAACCAGAAGA    71.5％

3884  UGAGUGUACAUCAAAACAU    74.0％    3938  ACUCACAUGAUGAUCUGGC    71.5％

3885  UUGCGUUAAAUGAGAACAU    74.0％    3939  AGGUGCAAAACCAGAAGAA    71.5％

3886  AAUUGCUUCAAAUGAGAAC    73.9％    3940  GUGGAUGGCAUGCCAUUCU    71.3％

3887  AACAGAGGGCCUCCGCAGG    73.9％    3941  AUGGCAUGCCAUUCUGCUG    71.3％

3888  UGCUUCAAAUGAGAACAUG    73.9％    3942  UGGCAUGCCAUUCUGCUGC    71.3％

3889  AGGGCCUCCGCAGGCCAAA    73.9％    3943  GAUGGCAUGCCAUUCUGCU    71.3％

3890  CAACAGAGGGCCUCCGCAG    73.9％    3944  GAACUUAAACUCAGUGAUU    71.2％

3891  UAGACCCUUUCAAACUACU    73.9％    3945  ACUUAAACUCAGUGAUUAU    71.2％

3892  AAUCAACAGAGGGCCUCCG    73.8％    3946  UUCGGAGACAAUGCAGAAG    71.2％

3893  AUCAACAGAGGGCCUCCGC    73.8％    3947  AUCCUAAGAAAACUGGAGG    71.2％

3894  UCAACAGAGGGCCUCCGCA    73.8％    3948  CCAGAAUGCAACUGAGAUU    71.2％

3895  AGAACCUUUCAAACUACUU    73.8％    3949  CUCACUGAGUGACAUCAAA    71.2％

3896  GGGGAGUUUUCGAGCUCUC    73.6％    3950  UCGGAGACAAUGCAGAAGA    71.2％

3897  AUAGACCCUUUCAAACUAC    73.6％    3951  AACUUAAACUCAGUGAUUA    71.2％

3898  GAGUUUUCGAGCUCUCAGA    73.6％    3952  GAUCCUAAGAAAACUGGAG    71.1％

3899  ACAGAGGGCCUCCGCAGGC    73.5％    3953  CAGCUGGUCUAACUCACAU    71.0％

3900  GGAGUUUUCGAGCUCUCAG    73.5％    3954  GAAUGCAACUGAGAUUAGG    71.0％

3901  CAGAGGGCCUCCGCAGGCC    73.5％    3955  ACAGCUGGUCUAACUCACA    71.0％

3902  AGAGGGCCUCCGCAGGCCA    73.5％    3956  CAUUCUGCUGCAUUUGAAG    70.9％

3903  AAUAGACCCUUUCAAACUA    73.4％    3957  AUGCCAUUCUGCUGCAUUU    70.8％

3904  GGGAGUUUUCGAGCUCUCA    73.4％    3958  GCCAUUCUGCUGCAUUUGA    70.8％

3905  UCACUGAGUGACAUCAAAA    73.4％    3959  CAUGCCAUUCUGCUGCAUU    70.8％

3906  GAGGGCCUUCGCAGGCCAA    73.4％    3960  CCAUUCUGCUGCAUUUGAA    70.8％

3907  UAAUCAACAGAGGGCCUCC    73.3％    3961  UGCCAUUCUGCUGCAUUUG    70.8％

3908  CUGAGUGACAUCAAAAUCA    73.1％    3962  GCAUGCCAUUCUGCUGCAU    70.8％

3909  ACUGAGUGACAUCAAAAUC    73.1％    3963  GGCAUGCCAUUCUGCUGCA    70.8％

3910  CACUGAGUGACAUCAAAAU    73.0％    3964  UGGAGAGGUGAGAAUGGGC    70.8％

3911  AUCGAAGAUCUCAUAUUUU    72.9％    3965  GGAGAGGUGAGAAUGGGCG    70.8％

3912  UUGUUAAGCUUCAUCAGAG    72.6％    3966  CUGGAGAGGUGAGAAUGGG    70.8％

3913  GAUGAUUGAUGGAAUUGGG    72.6％    3967  CAAAUGAGAACAUGGAUAA    70.6％

3914  UGUUAAGCUUCAUCAGAGG    72.6％    3968  UAAGGACCAGGAGUGGAGG    70.6％

3915  UUCGAAAAAGAGGGAUAUU    72.3％    3969  AUAAGGACCAGGAGUGGAG    70.6％

3916  UCGGAAAAGAGGGAUAUUC    72.3％    3970  AAGGACCAGGAGUGGAGGA    70.5％

3917  ACAAAUUGCUUCAAAUGAG    72.3％    3971  AGGACCAGGAGUGGAGGAA    70.5％

3972    GAAAAAGAGAGAUAUUCCU    70.5％    3987  GUUUUCGAGCUCUCAGACG    70.3％

3973    CGAAGACAAUGCAGAAGAG    70.5％    3988  GCUGCAUUCAAGGAAUUCG    70.3％

3974    CGAAAAAGAGGGAUAUUCC    70.5％    3989  AGAAAGUCGGAACCCAGGA    70.3％

3975    GCCUGUGUGUAUGGACCUG    70.5％    3990  AAAGUCGGAACCCAGGAAA    70.3％

3976    AAAAAGAGGGAUAUUCCUU    70.5％    3991  AACAGCUUGACAAUAGAGA    70.2％

3977    CCUGUGUGUAUGGACCUGC    70.5％    3992  GGAGACAAUGCAGAAGAGU    70.2％

3978    GAGAAAGUCGGAAGCCAGG    70.4％    3993  AGAUUGUUAGCUUCACUCA    70.1％

3979    AGAGAAAGUCGGAACCCAG    70.4％    3994  GAUUGUUAAGCUUCAUCAG    70.1％

3980    AAAUGAGAACAUGGUAAAU    70.4％    3995  UGGAAGAACACCCCAGCGC    70.1％

3981    CUUCGAAAAAGAGGGAUAU    70.4％    3996  CUGCCUGUGUGUAUGGACC    70.0％

3982    GGACCAGGAGUGGAGGAAA    70.4％    3997  CUGGAAGAACACCCCAGCG    70.0％

3983    UUUUCGAGCUCUCAGACGA    70.3％    3998  GAGACAAUGCAGAAGAGUA    70.0％

3984    CUGCAGUCAAAGGAAUCGG    70.3％    3999  AAUGAGAACAUGGAUAAUA    70.0％

3985    AGUUUUCGAGCUCUCAGAC    70.3％    4000  AUGAGAACAUGGAUAAUAU    70.0％

3986    GAAAGUCGGAACCCAGGAA    70.3％    4001  CCUGCCUGUGUGUAUGGAC    70.0％

表2-6在表1-6所列甲型流感片段2(NA)序列中以至少70％存在的保守19-mer序列

Seq

      序列    百分比                   4035    AGCUCAAGUUGUCACGAUG    85.8％

                                       4036    CAGAGACAACUGGAAAGGC    85.8％

4002  CAGGCUCAUGGCCUGAUGG    87.4％    4037    GAAUGCGUUUGUAUCAAUG    85.7％

4003  GUGGACCUCAAACAGUAUU    87.4％    4038    AAUGCGUUUGUAUCAAUGG    85.7％

4004  UAGCAUGGUCCAGCUCAAG    87.3％    4039    AGUAUUGUUGUGUUUUGUG    85.6％

4005  UGGACCUCAAACAGUAUUG    87.3％    4040    GUAUUGUUGUGUUUUGUGG    85.6％

4006  ACAGGCUCAUUGGCCGAUG    87.2％    4041    UCAAGUUGUCACGAUGGAA    85.5％

4007  GGACCUCAAACAGUAUUGU    87.1％    4042    GUUGUCACGAUGGAAAAGC    85.5％

4008  UGGUCCAGCUCAAGUUGUC    87.0％    4043    CAGUAUUGUUGUGUUUUGU    85.5％

4009  GACCUCAAACAGUUUUGUU    87.0％    4044    AUUGGUCAAAGCCGCAAUG    85.5％

4010  GGUCCAGCUCAAGUUGUCA    87.0％    4045    CAAGUUGGUACGAUGGAAA    85.5％

4011  CAUGGUCCAGCUCAAGUUG    87.0％    4046    ACAGUAUUGUUGUGUUUUG    85.5％

4012  GCAUGGUCCAGCUCAAGUU    87.0％    4047    AACAGUAUUGUUGUGUUUU    85.5％

4013  ACCUCAAACAGUAUUGUUG    87.0％    4048    AAUUGGUCAAAGCCGCAAU    85.5％

4014  AGCAUGGUCCAGCUCAAGU    87.0％    4049    AAACAGUAUUGUUGUGUUU    85.4％

4015  AUGGUCCAGCUCAAGUUGU    86.7％    4050    AGUUGUCACGAUGGAAAAG    85.4％

4016  CCAGUUAUGUGUGCUCAGG    86.4％    4051    CUCAAGUUGUUCACGUGGA    85.4％

4017  CAAACAGUAUUGUUGUGUU    86.4％    4052    AAGUUUGUGAGAUGGAAAA    85.3％

4018  UCAACAUAUUGUGUUGUGU    86.4％    4053    CAACUGCUAGCUUCAUUUA    85.1％

4019  CCUCAAACAGUAUUGUUGU    86.4％    4054    GCAACUGCUAGCUUCAUUU    85.1％

4020  UCCAGUUAUGUGUGCUCAG    86.4％    4055    AAUGCAACUGCUAGCUUCA    84.9％

4021  UUCCAGUUAUGUGUGCUCA    86.3％    4056    UGCAACUGCUAGCUUCAUU    84.9％

4022  UCUGCAGAGACAACUGGAA    86.1％    4057    AUGCAACUGCUAGCUUCAU    84.9％

4023  UGCAGAGACAACUGGAAAG    86.1％    4058    GAACCUUAUGUGUCAUGCG    84.8％

4024  GCAGAGACAACUGGAAAGG    86.1％    4059    AACGUUAUGUGUCAUGCGA    84.7％

4025  CUCAAACAGUAUUGUUGUG    86.1％    4060    AAUCCAAAUCAAAAGAUAA    84.7％

4026  CUGCAGAGACAACUGGAAA    86.1％    4061    AUCCAAAUCAAAAGAUAAU    84.7％

4027  GUCCAGCUGAAGUUGUCAC    86.0％    4062    AAAUGCAACUGCUAGCUUA    84.7％

4028  GAGACAACUGGAAAGGCUC    86.0％    4063    UCCAAAUCAAAAGAUAAUA    84.6％

4029  GCUCAAGUUGUCACGAUGG    85.9％    4064    CAAAUCAAAAGAUAAUAAC    84.5％

4030  CCAGCUCAAGUUGUGACGA    85.9％    4065    AUAGCAUGGUCCAGCUCAA    84.5％

4031  UCCAGCUCAAGUUGUCACG    85.9％    4066    CCAAAUCAAAAGAUAAUAA    84.5％

4032  CAGUAGUAUGGACUGAUGG    85.9％    4067    ACAGUAGUAAUGACUGAUG    84.4％

4033  CAGCUCAAGUUGUCACGAU    85.8％    4068    GUCACGAUGGAAAAGCAUG    84.2％

4034  AGAGACAACUGGAAAGGCU    85.8％

4069    UUGGUCAAAGCCGCAAUGU    84.2％    4123    CUCAUGGCCUGAUGGGGCG    82.7％

4070    GUGGAGUUGAUAAGGGGAA    84.2％    4124    AAAUUGGUCAAAGCCGCAA    82.7％

4071    UCACGAUGGAAAAGCAUGG    84.2％    4125    CAGGAUUUGCACCUUUUUC    82.7％

4072    UGGAGUUGAUAAGGGGAAG    84.1％    4126    ACAGGAUUUCACCUUUUUU    82.7％

4073    UGUCACGAUGGAAAAGCAU    84.1％    4127    AACAGGCUCAUGGCCUGAU    82.7％

4074    GAGAACCUUAUUGUCUCAG    84.0％    4128    GGAAAAGCAUGGCUGCAUG    82.6％

4075    AGAGAACCUUAUGUGUCAU    84.0％    4129    GAAAAGCAUGGCUGCAUGU    82.6％

4076    UUGUCACGAUGGAAAAGCA    83.9％    4130    AAAAGCAUGGCUGCAUGUU    82.6％

4077    ACCUUAUGUGUCAUGCGAU    83.8％    4131    UGGAAAAGCAUGGCUGCAU    82.5％

4078    CCUUAUGUGUCAUGCGAUC    83.8％    4132    AUGGAAAAGCAUGGCUGCA    82.5％

4079    AGGCUCAUGGCCUGAUGGG    83.8％    4133    GAUGGAAAAGCAUGGCUGC    82.4％

4080    UUUUAUGUGGAGUUGAUAA    83.8％    4134    GUGGAUGGGAAGAACGAUC    82.4％

4081    GGCUCAUGGCCUGAUGGGG    83.8％    4135    CAGAAAUUGGUCAAAGCCG    82.3％

4082    UUUAUGUGGAGGUGAUAAG    83.8％    4136    UACAGGAUUUGCACCUUUU    82.2％

4083    GGUGCUUUUAUGUGGAGUU    83.7％    4137    CGUGUGGAUGGGAAGAACG    82.0％

4084    ACGUGUGGAUGGGAAGAAC    83.6％    4138    CAUAACAGAGAUAGUGUAU    81.8％

4085    AACAUUAACAGGAUAGUGU    83.6％    4139    UUAUGUGUCAUGCGAUCCU    81.8％

4086    ACAUAACAGAGAUAGUGUA    83.6％    4140    CUUAUGUGUCAUGCGAUCC    81.8％

4087    AUGACGUGUGGAUGGGAAG    83.6％    4141    GGAUUUGCACCUUUUUCUA    81.5％

4088    UGAUUGUUGUGUUUGUGGC    83.5％    4142    CACGAUGGAAAAGCAUGGC    81.5％

4089    UGACGUGUGGAUGGGAAGA    83.5％    4143    ACGAUGGAAAAGCAUGGCU    81.5％

4090    GACGUGUGGAUGGGAAGAA    83.5％    4144    UGGAUGGGAAGAACGAUCA    81.4％

4091    AUUGUUGUGUUUUGUGGCA    83.5％    4145    GAUUUGCACCUUUUUCUAA    81.4％

4092    UUGUUGUGUUUUGUGGCAC    83.5％    4146    AUUUGCACCUUUUUCUAAG    81.4％

4093    UACAGAAAUUGGUCAAAGC    83.4％    4147    UUGCACCUUUUUCUAAGGA    81 4％

4094    AAAAUGCAACUGCUAGCUU    83.4％    4148    CGAUGGAAAAGCAUGGCUG    81.4％

4095    ACAGAAAUUGGUCAAAGCC    83.4％    4149    UUUGCACCUUAUUCUAAGG    81.4％

4096    AUGUGGAGUUGAUAAGGGG    83.3％    4150    UAUGUGUCAUGCGAUCCUG    81.3％

4097    GCUUUUAUGUGGAGUUGAU    83.3％    4151    UGAAUCCAAAUCAAAAGAU    81.3％

4098    UAUGUGGAGUUGAUAAGGG    83.3％    4152    AUGAAUCCAAAUCAAAAGA    81.3％

4099    UGUGGAGUUGAUAAGGGGA    83.3％    4153    GAAUCCAAAUCAAAAGAUA    81.3％

4100    CUUUUAUGUGGAGUUGAUA    83.3％    4154    GGAUGGGAAGAACGAUCAG    80.5％

4101    GUGCUUUUAUGUGGAGUUG    83.3％    4155    UGAAAGGCUGGGCCUUUGA    80.1％

4102    UGCUUUUAUGUGGAGUUGA    83.3％    4156    GAGUGAAAGGCUGGGCCUU    80.0％

4103    UGUGGAUAUGGAAAACGAU    83.3％    4157    GGAGUGAAAGGCUGGGCCU    80.0％

4104    AGAACCUUAUGUGUCAUGC    83.2％    4158    GUGAAAGGCUGGGCCUUUG    80.0％

4105    UUAUGUGGAGUUGAUAAGG    83.1％    4159    UGCACCUUUUUCUAAGGAC    79.8％

4106    AUUACAGGAUUUGCACCUU    83.1％    4160    GCACCUUUUUCUAAGGACA    79.8％

4107    AUACAGAAAUUGGUCAAAG    83.1％    4161    CACCUUUUUCUAAGGACAA    79.8％

4108    UUACCAGGAUUGCACCUUU    83.1％    4162    CAUGGCUGCAUGUUUGUGU    79.8％

4109    AAAGCAUGGCUGCAUGUUU    83.1％    4163    AGUGAAAGGCUGGGCCUUU    79.8％

4110    AAGCAUGGCUGCAUGUUUG    83.1％    4164    GCAUGGCUGCUAUGUUUUG    79.8％

4111    GUGUGGAUGGGAAGAACGA    83.1％    4165    ACCUUUUUCUAAGGACAAU    79.8％

4112    AGCAUGGCUGCAUGUUUGU    83.1％    4166    CCUUUUUCUAAGGACAAUU    79.7％

4113    AUGGAACAGGCUCAUGGCC    83.0％    4167    GAUGGGAAGAACGAUCAGC    79.7％

4114    UAUGGUAACAGGCCAUGGC    83.0％    4168    CUUUUUCUAAGGACAAUUC    79.7％

4115    GCUCAUGGCCUGAUGGGGC    82.9％    4169    UAACUACUGUAACAUUGCA    79.3％

4116    GAAUACAGAAAUUGGUCAA    82.9％    4170    CUACUGUAACAUUGCAUUU    79.3％

4117    AAUACAGAAAUUGGUCAAA    82.9％    4171    ACUACUGUAACAUUGCAUU    79.3％

4118    UGGAACAGGCUCAUGGCCU    82.9％    4172    AACUACUGUAACAUUGCAU    79.0％

4119    GAAAUUGGUCAAAGCCGCA    82.8％    4173    GAAAUGACGUGUGGAUGGG    78.6％

4120    GGAACAGGCUCAUGGCCUG    82.8％    4174    GGAAAUGACGUGUGGAUGG    78.5％

4121    AGAAAUUGGUCAAAGCCGC    82.8％    4175    UGGAAAUGACGUGUGGAUG    78.4％

4122    GAACAGGCUCAUGGCCUGA    82.8％    4176    AUGGAAAUGACGUGUGGAU    78.4％

4177    GAUGGAAAUGACGUGUGGA    78.3％    4231    UUUCCAGUUAUGUGUGCUC    75.8％

4178    AAAUGACGUGUGGAUGGGA    78.2％    4232    GUCAGGAAGUGCUCAGCAU    75.8％

4179    AUGACGUGUGGAUAGGGAA    78.2％    4233    GGUGUCAGAUGUGUCUGCA    75.6％

4180    GUACAGUAGUAAUGACUGA    78.0％    4234    CUGGUGUCAGAUGUGUCUG    75.6％

4181    UGUACAGUAGUAAUGACUG    78.0％    4235    GUGUCAGAUGUGUCUGCAG    75.6％

4182    AGGAUUUGCACCUUUUUCU    78.0％    4236    UGGUGUCAGAUGUGUCUGC    75.5％

4183    CUUGUACAGUAGUAAUGAC    78.0％    4237    GUUUCCAGUUAUGUGUGCU    75.5％

4184    ACUUGUUACAUAGUAAUGA    77.9％    4238    GCAUUGUUUCCAGUUAUGU    75.5％

4185    UACAUUAGUAAUGACUGAU    77.9％    4239    AGCAUUGUUUCCAGUUAUG    75.5％

4186    UUGUACAGUAGUAAUGACU    77.9％    4240    GUACAUAUGGAACAGGCUC    75.5％

4187    AACUGCUAGCUUCAUUUAC    77.9％    4241    UGUUUCCAGUUAUGUGUGC    75.4％

4188    GUUAUUCUGGUAUUUUCUC    77.6％    4242    GUCAGAUGUGUCUGCAGAG    75.4％

4189    GGUUAUUCUGGUAUUUUCU    77.6％    4243    GGUACAUAUGGAACAGGCU    75.4％

4190    AUACUAAAAUACUAUUCAU    77.2％    4244    UGUCAGAUGUGUCUGCAGA    75.4％

4191    GAUACUAAAAUACUAUUCA    77.1％    4245    CCUGGUGUCAGAUGUGUCU    75.4％

4192    UACUAAAAUACUAUUCAUU    77.1％    4246    CAUAUGGAACAGGCUCAUG    75.3％

4193    AUGAAACCUUCAAAGUCAU    77.0％    4247    UACAUAUGGAACAGGCUCA    75.3％

4194    UCAGAUUGUGCUGCAGAGA    76.9％    4248    CAGGUACAUAUGGAACAGG    75.3％

4195    CUGAUACUAAAAUACUAUU    76.9％    4249    ACUGGAAAGGCUCCAAUAG    75.3％

4196    UCAAUCUCAUGCCUAUAUA    76.9％    4250    AUAUGGAACAGGCUCAUGG    75.3％

4197    CAGGAAGUGCUCAGCAUGU    76.9％    4251    AGGUACAUAUGGAACAGGC    75.3％

4198    AUCAAUCUCAUGCCUAUAU    76.9％    4252    AUAGCAUUGUUUCCAGUUA    75.3％

4199    CAAUCUCAUGCCUAUAUAA    76.9％    4253    UUGUUUCCAGUUAUGUGUG    75.3％

4200    UAUGAAACCUUCAAAGUCA    76.9％    4254    UAGCAUUGUUUCCAGUUAU    75.3％

4201    CAGAUGUGUCUGCAGAGAC    76.8％    4255    UCAGGUACAUAUGGAACAG    75.2％

4202    GCUGAUACUAAAAUACUAU    76.8％    4256    AACUGGAAAGGCUCCAAUA    75.2％

4203    ACUAAAAUACUAUUCAUUG    76.7％    4257    AUUGUUUCCAGUUAUGUGU    75.2％

4204    UGAUACUAAAAUACUAUUC    76.7％    4258    ACAUAUGGAACAGGCUCAU    75.2％

4205    AGAUGUGUCUGCAGAGACA    76.7％    4259    CAUUGUUUCCAGUUAUGUG    75.1％

4206    CUAAAAUACUAUUCAUUGA    76.7％    4260    CUGGAAAGGCUCCAAUAGG    75.1％

4207    GAUGUGUCUGCAGAGACAA    76.7％    4261    GACAACUGGAAAGGCUCCA    75.1％

4208    UCAGGAAGUGCUCAGCAUG    76.6％    4262    UAGAAAGAAACAUAACAGA    75.1％

4209    ACUGUAACAUUGCAUUUCA    76.3％    4263    ACAACUGGAAAGGCUCCAA    75.1％

4210    UAACAUUGCACUUCAAGCA    76.3％    4264    CAACUGGAAAGGCUCCAAU    75.1％

4211    AGCUGAUACUAAAAUACUA    76.3％    4265    AGAAAGAAACAUAACAGAG    74.9％

4212    GUAACAUU3CAUUUCAAGC    76.2％    4266    AAAGAAACAUAACAGAGAU    74.9％

4213    GGAAAGGCUCCAAUAGGCC    76.2％    4267    GAAAGAAACAUAACAGAGA    74.9％

4214    UGGAAAGGCUCCAAUAGGC    76.2％    4268    AGACAACUGGAAAGGCUCC    74.9％

4215    ACACACCCAGAAAAAACGA    76.1％    4269    AAAGGCUCCAAUAGGCCCA    74.6％

4216    UGUAACAUUGCAUUUCAAG    76.1％    4270    GAAACAUAACAGAGAUAGU    74.6％

4217    CUGUAACAUUGCAUUUCAA    76.1％    4271    AGAAACAUAACAGAGAUAG    74.6％

4218    GACACACCCAAGAAAAACG    76.1％    4272    AAGGCUCCAAUAGGCCCAU    74.6％

4219    UGUCAGGAAGUGCUCAGCA    76.0％    4273    AAGAAACAUAACAGAGAUA    74.6％

4220    ACACCCAGAAAAAACGACA    76.0％    4274    ACCUCAGGUACAUAUGGAA    74.4％

4221    UGUCUGCAGAGACAACUGG    75.9％    4275    CCUCAGGUACAUAUGGAAC    74.3％

4222    UGUGUCUGCAGAGACAACU    75.9％    4276    CUCAGGUACAUAUGGAACA    74.3％

4223    CACCCAGAAAAAACGACAG    75.9％    4277    UCUGUGAACAUUGCAUUUC    74.1％

4224    CAUGGCCUGAAUGGGCGGA    75.9％    4278    UACAUGAUAGGACCCCUUA    73.8％

4225    GUCUGCAGAGACAACUGGA    75.9％    4279    CAUAGCAUGGUCCAGCUCA    73.5％

4226    GUGUCUGCAGAGACAACUG    75.9％    4280    AUGGGAGAACGAUUCAGCG    73.5％

4227    UCAUGGCCUGAUGGGGCGG    75.9％    4281    UGCAUAGCAUGGUCCAGCU    73.5％

4228    GAAAGGCUCCAAUAGGCCC    75.9％    4282    GCAUAGCAUGGUCCAGCUC    73.5％

4229    CACACCCAGAAAAAACGAC    75.9％    4283    UUGUCAGGAAGUGCUCAGC    73.3％

4230    AUGUGUCUGCAGAGACAAC    75.8％    4284    UGGGAAGAACGAUCAGCGA    73.3％

4285    AUUUGUCAGAAGUGCUCAG    73.3％    4339    UAUGUGUGCUCAGGACUUG    71.9％

4286    CUUGUUGGAGACACACCCA    72.9％    4340    UGUGCUCAGGACUUGUUGG    71.9％

4287    GUGCUAGGCAUGGUCCAGC    72.9％    4341    GAUAUCCUGGUGUCGAAUG    71.9％

4288    GUGUGCAUAGCAUGGUCCA    72.9％    4342    AAUCGGUGCUUUUAUGUGG    71.8％

4289    UUGUUGGAGACACACCCAG    72.9％    4343    UGUGUGCUCAGGACUUGUU    71.8％

4290    UGUGCAUAGCAUGGUCCAG    72.9％    4344    CUCGAUAUCCUGGUGUCAG    71.8％

4291    UGUUGGAGACACACCCAGA    72.9％    4345    AGUUGUGUGUGCUCAGGAC    71.8％

4292    GUUGGAGACACACCCAGAA    72.9％    4346    GUGUGCUCAGGACUUGUUG    71.8％

4293    AAGUGUGCAUAGCAUGGUC    72.8％    4347    AUCGGUGCUUUUAUGUGGA    71.8％

4294    AGUGUGCAUAGCAUGGUCC    72.8％    4348    GCAAGUGUGCAUAGCAUGG    71.8％

4295    UUGGAGACACACCCAGAAA    72.8％    4349    UUUUGUGGCACCUCAGGUA    71.7％

4296    CAAGUGUGCAUAGCAAGGU    72.7％    4350    CCUCGAUAUCCUGGUGUCA    71.7％

4297    GGAGACAACCCAGAAAAAA    72.6％    4351    AUCAAUCGGUGCUUUUAUG    71.7％

4298    UGGAGACACACCCAGAAAA    72.6％    4352    UCGAUAUCCUGGUGGUGAG    71.7％

4299    AAACAUAACAGAGAUAGUG    72.4％    4353    GUUUUGUGGCACCUCAGGU    71.7％

4300    AGAAUACAGAAAUUGGUCA    72.4％    4354    UUUGUGGCACCUCAGGUAC    71.7％

4301    UCCGGUUAUUCUGGUAUUU    72.4％    4355    CAAUCGGUGCUUUUAUGUG    71.7％

4302    AUUAUAGCAUUGUUUCCAG    72.4％    4356    UUGUGGCACCUCAGGUACA    71.6％

4303    UAUAGCAUUGUUUCCAGUU    72.4％    4357    CAGUUAGUGUGCUCAGGAA    71.5％

4304    GGGAAGAACGAUCAGCGAG    72.4％    4358    ACCCAGAAAAACGACCAGC    71.5％

4305    CCGGUUAUUCUGGUAUUUU    72.4％    4359    CCCAGAAAAAACGAGAGCU    71.5％

4306    UUAUAGCAUUGUUUCCAGU    72.4％    4360    GCAUCAAUCGGUGCUUUUA    71.4％

4307    CAGUACAUGAUAGGACCCC    72.3％    4361    UUGUGUUUUGUGGCACCUC    71.4％

4308    UGCGUUUGUAUCAAUGGAA    72.3％    4362    CAUCAAUCGGUUCUUUUAU    71.4％

4309    GAUUAUGCAUUUUGUUCCA    72.3％    4363    UCCUCGAUAUCCUGGUGUC    71.4％

4310    GGCUGCAUGUUUGUGUAAC    72.2％    4364    UGCAUCAAUCGGUGCUUUU    71.4％

4311    CACCUCAGGUACAUAUGGA    72.2％    4365    AUCCUCGAUAUCCUGGUGU    71.4％

4312    GUACAUGAUAGGACCCCUU    72.2％    4366    UAUCCUCGAUAUCCUGGUG    71.4％

4313    UGGGCACCUCAGGUUACAU    72.2％    4367    GCUCAGGACUUGUUGGAGA    71.3％

4314    CGGUUAUUCUGGUAUUUUC    72.2％    4368    UGGUCAGGACUUGUUGGAG    71.3％

4315    GAGACACACCCAGAAAAAA    72.2％    4369    GUUGUGUUUUGUGGCACCU    71.3％

4316    GGCACCUCAGGUACAUAUG    72.2％    4370    UGUUGUGUUUUGUGGCACC    71.3％

4317    GUGGCACCUCAGGUACAUA    72.2％    4371    AUUGGCUCUGUUUCUCUCA    71.2％

4318    GCGUUUGUUAUCAAUGAAC    72.2％    4372    UGUGUUUUGUGGCACCUCA    71.2％

4319    UUUGUAUCAAUGGAACUUG    72.2％    4373    GGACUUGUUGGAGACACAC    71.2％

4320    ACAGUACAUGAUAGGACCC    72.2％    4374    GACUUGUUGGAGACACACC    71.2％

4321    GCACUCCAGGUUCAUAUGG    72.2％    4375    CAGGACUUGUUGGAGACAC    71.2％

4322    UGUGGCACCUCAGGUACAU    72.2％    4376    CUAGGACUUGUUGGGAGAC    71.2％

4323    UGGCUGCAUGUUUGUGUAA    72.2％    4377    AGGACUUGUUGGAGACACA    71.2％

4324    AGUACAUGAUAGGACCCCU    72.2％    4378    GUGUUUGUGGCACCUUCAG    71.2％

4325    GUUUUGUAUCAAUGAACUU    72.1％    4379    UCAGGACUUGUUGGAGACA    71.2％

4326    AUGCGUUUGUAUCAAUGGA    72.1％    4380    UGUUUUGUGGCACCUCAGG    71.2％

4327    ACACAGUACAUGAUAGGAC    72.0％    4381    ACUUGUUGGAGACACACCC    71.1％

4328    UUGUAUCAAUGGAACUUGU    72.0％    4382    UCAAUUGGAACUUUACAGU    71.0％

4329    CGUUUGUAUCAAUGGAACU    72.0％    4383    AUCAAUGGAACUUGUACAG    71.0％

4330    GUCCGGUUAUUCUGGUAUU    72.0％    4384    CUGCAUCAAUCGGUGCUUU    71.0％

4331    UCAAUCGGUGCUUUUAUGU    72.0％    4385    GUGCUCAGGACUUGAUGGA    70.9％

4332    CACGUACAUGACUAGGACC    72.0％    4386    GUUAUCAAUUUGCCCUUGG    70.8％

4333    AGACACACCCAGAAAAAAC    71.9％    4387    AAGCUGCAUCAAUCGGUGC    70.8％

4334    AUGUGUGCUCAGGACUUGU    71.9％    4388    GCUGCAUCAAUCGGUGCUU    70.8％

4335    GUUAUGUGUGCUCAGGACU    71.9％    4389    UGUUAUCAAUUUGCCCUUG    70.8％

4336    CGAUAUCCUGGUGUCAGAU    71.9％    4390    AAAAGCUGCAUCAAUCGGU    70.8％

4337    UUAUGUGUGCUCAGGACUU    7L9％     4391    AAAGCUGCAUCAAUCGGUG    70.8％

4338    AUAUCCUGGUGUCAGAUGU    71.9％    4392    AGCUGCAUCAAUCGGUGCU    70.8％

4393    UUGGCUCUGUUUCUCUCAC    70.7％    4410  GCAAAAGCUGCAUCAAUCG    70.4％

4394    GGUCCGGUUAUUCUGGUAU    70.7％    4411  AAGAGAACCUUAUGUGUCA    70.4％

4395    AGGUCCGGUUAUUCUGGUA    70.7％    4412  AUGACACAGUACAUGAUAG    70.3％

4396    CAAAAGCUGCAUCAAUCGG    70.6％    4413  AAUGACACAGUACAUGAUA    70.3％

4397    AUGGCUGCAUGUUUGUGUA    70.6％    4414  UUUGAAUGAUGAAAUGACG    70.3％

4398    UAUCAAUGGAACUUGACDA    70.6％    4415  UUAAAGAAAGAAACAUAAC    70.3％

4399    GUAUCAAUGGAACUUGUAC    70.6％    4416  AGGGAACAACACUAAACAA    70.3％

4400    UGUAUCAAUGGAACUUGUA    70.6％    4417  UAUCCUGGUGUCAGAUGUG    70.2％

4401    AAUAGAAAGAAACAUAACA    70.6％    4418  AUCCUGGUGUCAGAUGUGU    70.2％

4402    UCAUGGAGUGAAAGGCUGG    70.5％    4419  UCGGUGCUUUUAUGUGGAG    70.2％

4403    CAUGGAGUGAAAGGCUGGG    70.5％    4420  CAGGGAACAACACUAAACA    70.2％

4404    CAAGAGAACCUUAUGUGUC    70.5％    4421  GACACAGUACAUGAUAGGA    70.2％

4405    AUGGAGUGAAAGGCUGGGC    70.5％    4422  UUGAUGAUGGAAAUGACGU    70.2％

4406    AUAGAAAGAAACAUAACAG    70.5％    4423  GGGAACAACACUAAACAAC    70.1％

4407    ACAAGAGAACCUUAUGUGU    70.5％    4424  GGCAAAAGCUGCAUCAAUC    70.1％

4408    UGGAGUGAAAGGCUGGGCC    70.4％    4425  CAAAUGACACAGUACAUGA    70.0％

4409    UCAAAUGACACAGUACAUG    70.4％    4426  UCCUGUGUCUAGAUGUGUC    70.0％

表2-7在表1-7所列甲型流感片段2(M1&M2)序列中以至少70％存在的保守19-mer序列

Seq

ID    序列    百分比                   4459    GCUUUGUCCAAAAUGCCCU    94.3％

                                       4460    CGCUUUGUCCAAAAUGCCC    94.3％

4427  UUCACGCUCACCGUGCCCA    99.2％    4461    UCAGUUAUUCUGCUGGUGC    94.2％

4428  CAGGCCCCCUCAAAGCCGA    99.0％    4462    AUUCUGCUGGUGCACUUGC    94.1％

4429  UCAGGCCCCCUCAAAGCCG    99.0％    4463    CUCAUGGAAUGGCUAAAGA    94.1％

4430  UCACGCUCACCGUGCCCAG    98.9％    4464    UCAUGGAAUGGCUAAAGAC    94.1％

4431  CACGCUCACCGUGCCCAGU    98.8％    4465    UAUUCUGCUGGUGCACUUG    94.1％

4432  CGCUCACCGUGCCCAGUGA    98.8％    4466    AUGGAAUGGCUAAAGACAA    94.0％

4433  ACGCUCACCGUGCCCAGUG    98.8％    4467    CUCAGUUAUUCUGCUGGUG    94.0％

4434  UCACCGUGCCCAGUGAGCG    98.7％    4468    GUUAUUCUGCUGGUGCACU    94.0％

4435  CUCACCGUGCCCAGUGAGC    98.7％    4469    UGGCCAGCACUACAGCUAA    94.0％

4436  GCUCACCGUGCCCAGUGAG    98.5％    4470    UUAUUCUGCUGGUGCACUU    94.0％

4437  AUCUUGAGGCUCUCAUGGA    96.4％    4471    CAUGGAAUGGCUAAAGACA    94.0％

4438  GAUCUUGAGGCUCUCAUGG    96.4％    4472    UGGAAUGGCUAAAGACAAG    93.9％

4439  UGUCACCUCUGACUAAGGG    96.3％    4473    UCUCAUGGAAUGGCUAAAG    93.9％

4440  CUGUCACCUCUGACUAAGG    96.3％    4474    AGUUAUUCUGCUGGUGCAC    93.9％

4441  GACUGCAGCGUAGACGCUU    95.6％    4475    GGAAUGGCUAAAGACAAGA    93.7％

4442  GGACUGCAGCGUAGACGCU    95.6％    4476    AAUGGCUAAAGACAAGACC    93.7％

4443  UGCAGCGUAGACGCUUUGU    95.5％    4477    GAAUGGCUAAAGACAAGAC    93.7％

4444  ACUGCAGCGUAGACGCUUU    95.5％    4478    UCCAUGGGGCCAAAGAAAU    93.4％

4445  CUGCAGCGUAGACGCUUUG    95.5％    4479    GCGUAGACGCUUUGUCCAA    93.4％

4446  GCUAUGGAGCAAAUGGCUG    95.4％    4480    CAGUUAUUCUGCUGGUGCA    93.4％

4447  UGGCUAAAGACAAGACCAA    95.4％    4481    UUCCAUGGGGCCAAAGAAA    93.4％

4448  CAGCGUAGACGCUUUGUCC    95.4％    4482    CACCUCUGACUAAGGGGAU    93.2％

4449  CUAUGGAGCAAAUGGCUGG    95.4％    4483    GUCACCUCUGACUAAGGGG    93.2％

4450  AGCGUAGACGCUUUGUCCA    95.4％    4484    UCACCUCUGACUUAAGGGA    93.2％

4451  GCAGCGUAGACGCUUUGUC    95.4％    4485    CUGGUGCACUUGCCAGUUG    93.0％

4452  GGCUAAAGACAAGACCAAU    95.4％    4486    GAGGCUCUCAUGGAAUGGC    93.0％

4453  CGUAGACGCUUUGUCCAAA    94.9％    4487    GCUCUCAUUGGAAGGCUAA    93.0％

4454  GUAGACGGUUUGUCCAAAA    94.9％    4488    CUCUCAUGGAAUGGCUAAA    93.0％

4455  AGACGCUUUGUCCAAAAUG    94.8％    4489    AUGGGGCCAAAGAAAUAGC    93.0％

4456  UAGACGCUUUGUCCAAAAU    94.8％    4490    AGGCUCUCAUGGAAUGGCU    93.0％

4457  GACGCUUUGUCCAAAAUGC    94.7％    4491    GGCUCUCAUGGAAUGGCUA    92.9％

4458  ACGCUUUGUCCAAAAUGCC    94.3％

4492  UUGAGGCUCUCAUGGAAUG    92.9％    4546  GAUCUUCUUGAAAAUUUGC    88.6％

4493  UGAGGCUCUCAUGGAAUGG    92.9％    4547  UGAUCUUCUUGAAAAUUUG    88.6％

4494  CUUGAGGCUCUCAUGGAAU    92.9％    4548  CAGAAACGAAUGGGGGUGC    88.5％

4495  CAUGGGCCAAAGGAAAUAG    92.9％    4549  ACAAUGGGGGGUGCAGAUG    88.5％

4496  GCUGUGCACUUGCCAGGUU    92.9％    4550  AGAAACGAAUGGGGGUGCA    88.5％

4497  CUUCUACGGAAGGAGUACC    92.8％    4551  AAACGAAUUGGGGUGCAGA    88.4％

4498  UCUUGAGGCUCUCAUGGAA    92.7％    4552  AACGAAUGGGGGUGCAGAU    88.4％

4499  CUGCUGGUGCACUUGCCAG    92.7％    4553  UGGAGCAAAUGGCUGGAUC    88.4％

4500  UGCUGGUGCACUUGCCAGU    92.7％    4554  AUGGAGCAAAUGGCUGGAU    88.4％

4501  UCUGCUGGUGCACUUGCCA    92.7％    4555  GAAACGAAAUUGGGGGCAG    88.2％

4502  CCAUGGGGCCAAAGAAAUA    92.6％    4556  AUCGUCUUUUUUUCAAAUG    88.1％

4503  AGUAUAUGAGGGAAGAAUA    92.6％    4557  CCUAUCAGAAACGAAUGGG    88.1％

4504  CCUUCUACGGAAGGAGUAC    92.5％    4558  UAUGGAGCAAAUGGCUGGA    88.1％

4505  GUCUAUGAGGGAAGAAUAU    92.4％    4559  GAUCGUCUUUUUUUCAAAU    88.0％

4506  CUAUGAGGGAAGAAUAUCG    92.4％    4560  UGAUCGUCUUUUUUUCAAA    88.0％

4507  UCUAUGAGGGAAGAAUAUC    92.4％    4561  UUGAUCGUCUUUUUUUCAA    88.0％

4508  GUCAUUUUGUCAGCAUAGA    92.2％    4562  UCGUCUUUUUUUCAAAUGC    87.8％

4509  GAGUCUAUGAGGGAAGAAU    92.2％    4563  GAUUCUUGAUCGUCCUUUU    87.5％

4510  UCAUUUUGUCAGCAUAGAG    92.1％    4564  AUUCUUGAUCGUCUUUUUU    87.4％

4511  AGACUUGAAGAUGUCUUUG    91.9％    4565  CUUGAUCGUCUUUUUUUCA    87.2％

4512  GACUUGAAGAUGUCUUUGC    91.9％    4566  UUGGGACUCAUCUUAGCUC    87.2％

4513  AGAGACUUGAAGAUGUCUU    91.9％    4567  AUUGGGAUCUUGCACUUGA    87.1％

4514  GAGACUUGAAGAUGUCUUU    91.9％    4568  UCUUGAUCGUCUUUUUUUC    87.1％

4515  CAGAGACUUGAAGAUGUCU    91.9％    4569  UUCUUGAUCGUCUUUUUUU    87.1％

4516  GUGCAGAUGCAACGAUUCA    91.7％    4570  GAUGAUCUUCUUGAAAAUU    87.0％

4517  UUCUGCUGGUGCACUUGCC    91.7％    4571  UAUCGAAAGGAACAGCAGA    87.0％

4518  UGCAGAUGCAACGAUUCAA    91.6％    4572  AGAUGAUCUUCUUGAAAAU    86.9％

4519  UAUGAGGGAAGAAUAUCGA    91.5％    4573  UUGGGAUCUUGCACUUGAU    86.9％

4520  AUGGGGGUGCAGAUGCAAC    91.3％    4574  UGGGAUCUUGCACUUGAUA    86.9％

4521  UGGGGGUGCAGAUGCAACG    91.3％    4575  UCAUUGGGAUCUUGCACUU    86.6％

4522  ACCUCUGACUAAGGGGAUU    91.3％    4576  CAUUGGGAUCUUGCACUUG    86.5％

4523  UGGAUUCUUGAUCGUCUUU    91.1％    4577  CAGAUCUUGAGGCUCUCAU    86.4％

4524  GGAUUCUUGAUCGUCUUUU    91.1％    4578  CACAGAUCUUGAGGCUCUC    86.4％

4525  GGGGUGCAGAUGCAACGAU    90.8％    4579  CCUGAGUCUAUGAGGGAAG    86.4％

4526  GGGUGCAGAUGCAACGAUU    90.8％    4580  ACAGAUCUUGAGGCUCUCA    86.4％

4527  GUGGAUUCUUGAUCGUCUU    90.8％    4581  AUCAUUGGGAUCUUGCACU    86.4％

4528  GGUGCAGAUGCAACGAUUC    90.8％    4582  CUAGUCUUAUGAGGGAAGA    86.4％

4529  GGGGGUGCAGAUGCAACGA    90.8％    4583  AGAUCUUGAGGCUCUCAUG    86.4％

4530  CUCUGACUAAGGGGAUUUU    90.7％    4584  ACACAGUCUUUGAGGCUCU    86.4％

4531  CCUCUGACUAAGGGGAUUU    90.7％    4585  ACAGCUAAGGCUAUGGAGC    86.3％

4532  UGUGGAUUCUUGAUCGUCU    90.7％    4586  CAGCUAAGGCUAUGGAGCA    86.3％

4533  UCUUCUUGAAAAUUUGCAG    90.5％    4587  AACACAGAUCUUGAGGCUC    86.3％

4534  AUGGCUAAAGACAAGACCA    90.5％    4588  GGCUAUGGAGCUAAUGGCU    86.2％

4535  AUCUUCUUGAAAAUUUGCA    90.5％    4589  ACUACAGCUAAGGCUAUGG    86.2％

4536  GAAUGGGGGUGCAGAUGCA    90.4％    4590  AAGGCUAUGGAGCAAAUGG    86.2％

4537  CGAAUGGGGGUGCAGAUGC    90.2％    4591  AGGCUAUGGAGCAAAUGGC    86.2％

4538  AAUGGGGGUGCAGAUGCAA    90.2％    4592  CUACAGCUAAGGCUAUGGA    86.2％

4539  UUGAAGAUGUCUUUGCUGG    89.9％    4593  CCAGCACUACAGCUAAGGC    86.1％

4540  CUUGAAGAUGUCUUUGCUG    89.9％    4594  AGCCACUAAGCUAAGGCUA    86.1％

4541  ACUUGAAGAUGUCUUUGCU    89.7％    4595  CACUAGAGCGAAGGCUAUG    86.1％

4542  GAUCCAAAUAACAUGGACA    89.2％    4596  GCCAGCACUACAGCUAAGG    86.1％

4543  AUGAUCUUCUUGAAAAUUU    89.0％    4597  GCACUACAGCUAAGGCUAU    86.1％

4544  AGAUUGCUGACUCCCAGCA    88.8％    4598  CUAAGGCUAUGGAGCAAAU    86.0％

4545  CAGAUUGCUGACUCCCAGC    88.8％    4599  AAUAUCGAAAGGAACAGCA    86.0％

4600  UAAGGCUAUGGAGCAAAUG    86.0％    4654    UCAGAAACGAAUGGGGGUG    84.1％

4601  GCUAAGGCUAUGGAGCAAA    86.0％    4655    CUAUCAGAAACGAAUGGGG    84.1％

4602  GUGAACAGAUUGCUGACUC    86.0％    4656    CCAAAAUGCCCUCAAUGGG    84.1％

4603  UACAGCUAAGGCUAUGGAG    86.0％    4657    UAUCAGAAACGAAAGGGGG    84.1％

4604  UGUGAACAGAUUGCUGACU    86.0％    4658    ACGGAAGGAGUACCUGAGU    84.0％

4605  CAGCACUACAGCUAAGGCU    86.0％    4659    UUUGGCCUGGUAUGUGCAA    84.0％

4606  GAAUAUCGAAAGGAACAGC    86.0％    4660    UACGGAAGGAGUACCUGAG    83.9％

4607  AAGAUUGCUGACUUCCCAG    85.9％    4661    CGGAAGGAGUACCUGAGUC    83.9％

4608  UGAACAGAUUGCUGACUCC    85.9％    4662    UCUACGGAAGGAGUACCUG    83.7％

4609  GAACAGAUUGCUGACUCCC    85.9％    4663    CACUUGCCAGUUGCAUGGG    83.7％

4610  AACAGAUUGCUGACUCCCA    85.9％    4664    GCACUUGCCAGUUGCAUGG    83.7％

4611  UAUCAUUGGGAUCUUGCAC    85.8％    4665    CUACGGAAGGAGUACCUGA    83.7％

4612  ACAUGAGAACAGAAUGGUU    85.8％    4666    UUCUACGGAAGGAGUACCU    83.7％

4613  UACCUGAGUCUAUGAGGGA    85.6％    4667    GGAAGGAGUACCUGAGUCU    83.7％

4614  AUAUCGAAAGGAACAGCAG    85.5％    4668    GGUGCACUUGCCAGUUGCA    83.6％

4615  AUGAGGGAAGAAUAUCGAA    85.4％    4669    GUGCACUUGCCAGUUGCAU    83.6％

4616  UUGCUAGUCAGGCCAGGCA    85.4％    4670    UGCACUUGCCAGUUGCAUG    83.6％

4617  UGAGGGAAGAAUAUCGAAA    85.3％    4671    AGUACCUGAGUCUAUGAGG    83.5％

4618  GGGAAGAAUAUCGAAAGGA    85.3％    4672    GGAGUACCUGAGUCUAUGA    83.5％

4619  GGAAGAAUAUCGAAAGGAA    85.2％    4673    GAGUACCUGAGUCUAUGAG    83.5％

4620  AGGGAAGAAUAUCGAAAGG    85.2％    4674    CAGCAGAAUGCUGUGGAUG    83.4％

4621  AAGAAUAUCGAAAGGAACA    85.2％    4675    AGGAGUACCUGAGUCUAUG    83.3％

4622  GUACCUGAGUCUAUGAGGG    85.2％    4676    GAAGGAGUACCUGAGUCUA    83.2％

4623  GAAGAAUAUCGAAAGGAAC    85.2％    4677    ACAGCAGAAUGCUGUGGAU    83.1％

4624  UGUUCACGCUCACCGUGCC    85.2％    4678    GGAACAGCAGAAUGCUGUG    83.1％

4625  AGAAUAUCGAAAGGAACAG    85.2％    4679    GAACAGCAGAAUGCUGUGG    83.1％

4626  GUGUUCACGCUCACCGUGC    85.2％    4680    AACAGCAGAAUGCUGUGGA    83.1％

4627  GAGGGAAGAAUAUCGAAAG    85.1％    4681    AAGGAGUACCUGAGUCUAU    83.1％

4628  GUUCACGCUCACCGUGCCC    85.1％    4682    CUUGCCAGUUGCAUGGGCC    82.7％

4629  GGCCAGCACUACAGCUAAG    85.0％    4683    UUGCCAGUUGCAUGGGCCU    82.7％

4630  UGUGUUCACGCUCACCGUG    84.9％    4684    AGGAACAGCAGAAUGCUGU    82.7％

4631  UUGUGUUCACGCUCACCGU    84.9％    4685    UGCCAGUUGCAUGGGCCUC    82.3％

4632  UUUGUGUUCACGCUCACCG    84.9％    4686    GCCAGUUGCAUGGGCCUCA    82.3％

4633  UUGUCCAAAAUGCCCUCAA    84.8％    4687    CCAGUUGCAUGGGCCUCAU    82.3％

4634  ACCUGAGUCUAUGAGGGAA    84.8％    4688    CAGUUGCAUGGGCCUCAUA    82.1％

4635  UUUGUCCAAAAUGCCCUCA    84.8％    4689    UGAGUCUAUGAGGGAAGAA    82.1％

4636  AAUGCCCUCAAUGGGAAUG    84.6％    4690    ACUUGCCAGUUGCAUGGGC    82.1％

4637  AGCUAAGGCUAUGGAGCAA    84.6％    4691    UGGUGCACUUGCCAGUUGC    82.0％

4638  AUGCCCUCAAUGGGAAUGG    84.6％    4692    AAGAUGUCUUUGCUGGGAA    81.9％

4639  AGUUGCAUGGGCCUCAUAU    84.5％    4693    UGAAGAUCGUUUGCUUGGG    81.9％

4640  GCAUGGGCCUCAUAUACAA    84.5％    4694    GAAGAUGUCUUUGCUGGGA    81.9％

4641  UGCAUGGGCCUCAUAUACA    84.5％    4695    GUAUCAUUGGGAUCUUGCA    81.5％

4642  GUUGCAUGGGCCUCAUAUA    84.5％    4696    AGUAUCAUUGGGAUCUUGC    81.5％

4643  CUUUGUCCAAAAUGCCCUC    84.5％    4697    AAAUGGUGCAGGCAAUGAG    81.1％

4644  UUGCAUGGGCCUCAUAUAC    84.4％    4698    GCAGAAUGCUGUGGAUGCU    81.1％

4645  UCCAAAAUGGCCUCAAUGG    84.4％    4699    GGACUCAUCCUAGCUCCAG    81.1％

4646  GUCCAAAAUGCCCUCAAUG    84.4％    4700    AGAAUGCUGUGGAUGCUGA    81.1％

4647  UGUCCAAAAUGCCCUCAAU    84.3％    4701    AGCAGAAUGCUGUGGAUGC    81.1％

4648  AGUCAUUUUGUCAGCAUAG    84.2％    4702    GAAUGCUGUGGAUGCUGAC    81.1％

4649  AAAUGCCCUCAAUGGGAAU    84.2％    4703    CGAGUAUCAUUGGGAUCUU    81.1％

4650  AAAAUGCCCUCAAUGGGAA    84.2％    4704    GGGACUCAUCCUAGCUCCA    81.1％

4651  UUGGCCUGGUAUGUGCAAC    84.2％    4705    CAGAAUGCUGUGGAUGCUG    81.1％

4652  CAAAAUGCCCUCAAUGGGA    84.2％    4706    GCGAGUAUCAUUGGGAUCU    81.1％

4653  AUCAGAAACGAAUGGGGGU    84.1％    4707    UGGGACUCAUCCUAGCUCC    81.0％

4708  CAAAUGGUGCAGGCAAUGA     81.0％    4762  GUAUGUUCUCUCUAUCGUU    77.6％

4709  GAGUAUCAUUGGGAUCUUG     81.0％    4763  GUCAGGCCAGGCAAAUGGU    77.6％

4710  GACUCAUCCUAGCUCCAGU     80.9％    4764  AUGUUCUCUCUAUCGUUCC    77.6％

4711  AAUGCUGUGGAUGCUGACG     80.5％    4765  UAGUCAGGCCAGGCAAAUG    77.4％

4712  AGGCAAAUGGUGCAGGCAA     80.2％    4766  CUAGUCAGGCCAGGCAAAU    77.4％

4713  GCAAAUGGUGCAGGCAAUG     80.2％    4767  GCUAGUCAGGCCAGGCAAA    77.4％

4714  GGCAAAUGGUGCAGGCAAU     80.2％    4768  UGCUAGUCAGGCCAGGCAA    77.2％

4715  AUGCUGUGGAUGCUGACGA     80.1％    4769  UUGCUGACUCCCAGCACAG    77.1％

4716  CUGACUAAGGGGAUUUUGG     79.8％    4770  AUUGCUGACUCCCAGCACA    77.1％

4717  UCUGACUAAGGGGAUUUUG     79.8％    4771  GAUUGCUGACUCCCAGCAC    77.1％

4718  UGCACUUGAUAUUGUGGAU     79.8％    4772  GCUGACUCCCAGCACAGGU    77.1％

4719  UGACUAAGGGGAUUUUGGG     79.8％    4773  CAGAUGCAACGAUUCAAGU    77.1％

4720  GCACUUGAUAUUUGUGAUU     79.8％    4774  CUGACUCCCAGCACAGGUC    77.1％

4721  UUGCACUUGAUAUUGUGGA     79.6％    4775  GCAGAUGCAACGAUUCAAG    77.0％

4722  CGUAUGUUCUCUCUAUCGU     79.2％    4776  UGCUGACUCCCAGCACAGG    76.9％

4723  GAAACGUAUGUUCUCUCGA     79.2％    4777  GGAAUGGGGAUCCAAAUAA    76.8％

4724  AUAAUUGUGGAUUCUGAUC     79.2％    4778  GGGAAUGGGGAUCCAAAUA    76.8％

4725  ACGUAUGUUCUCUCUAUCG     79.2％    4779  GAGGGCCUUCUACGGAAGG    76.8％

4726  AACGUAUGUUCUCUCUAUC     792％     4780  AUCUUGCACUUGAUAUUGU    76.7％

4727  AAACGUAUGUUCUCUCUAU     79.2％    4781  UCUUGCACUUGAUAUUGUG    76.7％

4728  CCAGGCAAAUGGUGCAGGC     79.1％    4782  CUUGCACUUGAUAUUGUGG    76.7％

4729  GAUAUUGUGGUUUCUUGAU     79.1％    4783  AUGGGAAUGGGGAUCCAAA    76.6％

4730  UGAUAUUGUGGAUUCUUGA     79.1％    4784  AGGGCCUUCUACGGAAGGA    76.6％

4731  AGGUCGAAACGUAUGUUCU     79.1％    4785  AAUGGGAAUGGGGAUCCAA    76.6％

4732  GAGGUCGAAACGUAUGUUC     79.1％    4786  GAUGCAACGAUUCAAGUGA    76.5％

4733  GGUCGAAACGUAUGUUCUC     79.1％    4787  ACAUUCCAUGGGGCCAAAG    76.5％

4734  GUCGAAACGUAUGUUCUCU     79.1％    4788  AGAUGCAACGAUUCAAGUG    76.5％

4735  CGAAACGUAUGUUCUCUCU     79.1％    4789  AAAAGAGGGCCUUCUACGG    76.4％

4736  UCGAAACGUAUGUUCUCUC     79.1％    4790  CAUUCCAUGGGGCCAAAGA    76.4％

4737  UAUUGUGGAUUCUUGAUCG     79.0％    4791  AGGCAAAUGGUGGCAACAA    76.4％

4738  CACUUGAUAUUGUGGAUUC     78.9％    4792  GGCAAAUGGUGGCAACAAC    76.4％

4739  ACUUGAUAUUGUGGAUUCU     78.9％    4793  CAAAUGGUGGCACAAUCCA    76.3％

4740  CUUGAUUUGUUGGAUUCUU     78.9％    4794  AUUGCCUGGGGCCAAAGAA    76.3％

4741  GCCAGGCAAAUGGUGCAGG     78.9％    4795  AAAUGGUGGCAACAACCAA    76.3％

4742  UGUAUUAUGUUGAUUCUUG     78.7％    4796  AACUUAAGAGGGAGAUAAC    76.2％

4743  CGCAGAGACUUGAAGAUGU     78.7％    4797  AGAGGGCCUUCUACGGAAG    76.2％

4744  GCGCAGAGACUUGAAGAUG     78.7％    4798  UGGGAAUGGGGAUCCAAAU    76.2％

4745  GGCCAGGCAAAUGGUGCAG     78.6％    4799  AAGAGGGCCUUCUACGGAA    76.2％

4746  AGGCCAGGCAAAUGGUGCA     78.6％    4800  AAACUUAAGAGGGAGAUAA    76.2％

4747  AUUGUGGAUUCUUGAUCGU     78.5％    4801  AAAGAGGGCCUUCUACGGA    76.2％

4748  UUGUGGAUUCUUGAUCGUC     78.5％    4802  CAGUCAUUUUGUCAGCAUA    76.1％

4749  CAGGCAAAUGGUGCAGGCA     78.4％    4803  CCUGUCACCUCUGACUAAG    76.0％

4750  GGGCCUUCUACGGAAGGAG     78.4％    4804  GCAAAUGGUGGCAACAACC    76.0％

4751  GGCCUUCUACGGAAGGAGU     78.4％    4805  UGCUGUGGAUGCUGACGAC    75.9％

4752  CGCGCAGAGACUUGAAGAD     78.3％    4806  ACAGUCAUUUUGUCAGCAU    75.8％

4753  UCGCGCAGAGACUUGAAGA     78.3％    4807  AUCAGGCCCCCUCAAAGCC    75.6％

4754  AUCGCGCAGAGACUUGAAG     78.2％    4808  CCAUCAGGCCCCCUCAAAG    75.6％

4755  CAGGCCAGGCAAAUGGUGC     78.1％    4809  GGAUCUUGCACUUGAUAUU    75.6％

4756  GCAGAGACUUGAAGAUGUC     77.9％    4810  CAUCAGGCCCCCUCAAAGC    75.6％

4757  AUCCUGUCACCUCUGACUA     77.9％    4811  GGGAUCUGCACUUGAUUAU    75.6％

4758  UCCUGUCACCUCUGACUAA     77.8％    4812  GAUCUUGCACUUGAUAUUG    75.5％

4759  UCAGGCCAGGCAAAUGGUG     77.8％    4813  GGAUGCUGACGACAGUCAU    75.4％

4760  UAUGUUCUCUCUAUCGUUC     77.6％    4814  GCUGUGGAUGCUGACGACA    75.4％

4761  AGUCAGGCCAGGCAAAUGG     77.6％    4815  AUGCUGACGACAUCAUUUU    75.4％

4816  UGGAUGCUGACGACAGUCA    75.4％    4870  UUGAAAAUUUGCAGACCUA    74.0％

4817  GAUGCUGACGACAGUCAUU    75.4％    4871  CUUCUUGAAAAUUUGCAGA    74.0％

4818  CUGUGGAUGCUGACGACAG    75.3％    4872  UCUUGAAAAUUUGCAGACC    74.0％

4819  UGCUGACGACAGUCAUUUU    75.3％    4873  CUUGAAAAUUUGCAGACCU    74.0％

4820  UGUGGAUGCUGACGACAGU    75.3％    4874  UUCUUGAAAAUUUGCAGAC    74.0％

4821  GUGGAUGCUGACGACAGUC    75.3％    4875  UCGAAAGGAACAGCAGAAU    73.9％

4822  GCCUUCUACGGAAGGAGUA    75.2％    4876  CCCAGUGAGCGAGGACUGC    73.7％

4823  GCUGACGACAGUCAUUUUG    75.1％    4877  CAUUUUGUCAGCAUAGAGC    73.7％

4824  ACGACAGUCAUUUUGUCAG    75.0％    4878  CCAGUGAGCGAGGACUGCA    73.7％

4825  GACGACAGUCAUUUUGUCA    75.0％    4879  GUGCCCAGUGAGCGAGGAC    73.6％

4826  UGACGACAGUCAUUUUGUC    75.0％    4880  GCCCAGUGAGCGAGGACUG    73.6％

4827  CUGACGACAGUCAUUUUGU    75.0％    4881  UGCCCAGUGAGCGAGGACU    73.6％

4828  GACAGUCAUUUUGUCAGCA    75.0％    4882  CUUAAGAGGGAGAUAACAU    73.5％

4829  CGACAGUCAUUUUGUCAGC    75.0％    4883  UUAAGAGGGAGAUAACAUU    73.5％

4830  UGGUGGCAACAACCAAUCC    75.0％    4884  CACCGUGCCCAGUGAGCGA    73.4％

4831  AAUGGUGGCAACAACCAAU    74.9％    4885  AAUGGUGCAGGCAAUGAGA    73.4％

4832  GGUGGCAACAACCAAUCCA    74.9％    4886  AAGAGGGAGAUAACAUUCC    73.4％

4833  AUGGUGGCAACAACCAAUC    74.9％    4887  CGUGCCCAGUGAGCGAGGA    73.4％

4834  AAGACAAGACCAAUCCUGU    74.8％    4888  CCGUGCCCAGUGAGCGAGG    73.4％

4835  CAAGACCAAUCCUGUCACC    74.8％    4889  GAGGGAGAUAACAUUCCAU    73.4％

4836  UACGCAAAUGGUGGCAACA    74.8％    4890  AGAGGGAGAUAACAUUCCA    73.4％

4837  GACAAGACCAAUCCUGUCA    74.8％    4891  ACCGUGCCCAGUGAGCGAG    73.4％

4838  AGACAAGACCAAUCCUGUC    74.8％    4892  UGUUCUCUCUAUCGUUCCA    73.1％

4839  GACCAAUCCUGUCACCUCU    74.8％    4893  AAAAACACAGAUCUUGAGG    73.1％

4840  AGACCAAUCCUGUCACCUC    74.8％    4894  AUUUUGUCAGCAUAGAGCU    73.1％

4841  GCUAAAGACAAGACCAAUC    74.8％    4895  UUCUCUCUAUCGUUCCAUC    73.1％

4842  ACAAGACCAAUCCUGUCAC    74.8％    4896  GUUCUCUCUAUCGUUCCAU    73.1％

4843  AAGACCAAUCCUGUCACCU    74.8％    4897  GGAAAAACACAGAUCUUGA    73.0％

4844  AUAGGCAAAUGGUGGCAAC    74.7％    4898  AAACACAGAUCUUGAGGCU    73.0％

4845  UAAAGACAAGACCAAUCCU    74.7％    4899  GGGAAAAACACAGAUCUUG    73.0％

4846  AAAGACAAGACCAAUCCUG    74.7％    4900  AAAACACAGAUCUUGAGGC    73.0％

4847  CUAAAGACAAGACCAAUCC    74.7％    4901  UAAGAGGGAGAUAACAUUC    73.0％

4848  CAAUCCUGUCACCUCUGAC    74.6％    4902  GAUGUCUUUGCUGGGAAAA    72.9％

4849  CAUAGGCAAAUGGUGGCAA    74.6％    4903  GAAAAACACAGAUCUUGAG    72.9％

4850  AAGGAACAGCAGAAUGCUG    74.6％    4904  UCUCUCUAUCGUUCCAUCA    72.8％

4851  CCAAAUCCUGUCACCUCDA    74.6％    4905  UCCAUCAGGCCCCCUCAAA    72.8％

4852  ACAACCAAUCCAUUAAUAA    74.5％    4906  UUCCAUCAGGCCCCCUCAA    72.8％

4853  AUAACAUUCCAUGGGGCCA    74.4％    4907  CUCUCUAUCGUUCCAUCAG    72.8％

4854  UAACAUUCCAUGGGGCCAA    74.4％    4908  GUUCCAUCAGGCCCCCUCA    72.8％

4855  AGAUAACAUUCCAUGGGGC    74.4％    4909  UCUAUCGUUCCAUCAGGCC    72.8％

4856  GAGAUAACAUUCCAUGGGG    74.4％    4910  UGUCUUUGCUGGGAAAAAC    72.8％

4857  AACAUUCCAUGGGGCCAAA    74.3％    4911  UAUCGUUCCAUCAGGCCCC    72.8％

4858  CAACAACCAAUCCAUUAAU    74.3％    4912  GUCUUUGCUGGGAAAAACA    72.8％

4859  AACAACCAAUCCAUUAAUA    74.3％    4913  AUGUCUUUGCUGGGAAAAA    72.8％

4860  ACCAAUCCUGUCACCUCUG    74.2％    4914  UCUUUGCUGGGAAAAACAC    72.8％

4861  GAAAGGAACAGCAGAAUGC    74.2％    4915  CGUUCCAUUCAGGCCCCUC    72.8％

4862  AAAGGAACAGCAGAAUGCU    74.2％    4916  CUAUCGUUCCAUCAGGCCC    72.8％

4863  GGGAGAUAACAUUCCAUGG    74.1％    4917  CUCUAUCGUUCCAUCAGGC    72.8％

4864  CGAAAGGAACAGCAGAAUG    74.1％    4918  UCGUUCCAUCAGGCCCCCU    72.8％

4865  GGAGAUAACAUUCCAUGGG    74.1％    4919  AUCGUUCCAUCAGGCCCCC    72.8％

4866  AAUCCUGUCACCUCUGACU    74.1％    4920  UCUCUAUCGUUCCAUCAGG    72.8％

4867  AGGGAGAUAACAUUCCAUG    74.1％    4921  GGAUCAAGUGAGCAGGCAG    72.7％

4868  GAUAACAUUCCAUGGGGCC    74.1％    4922  CUAACCGAGGUCGAAACGU    72.7％

4869  AUCGAAAGGAACAGCAGAA    74.1％    4923  AUGGCUGGAUCAAGUGAGC    72.7％

4924  GAUCAAGUGAGCAGGCAGC    72.7％    4973  GGCUGGAUCAAGUGAGCAG    71.5％

4925  UGGCUGGAUCAAGUGAGCA    72.7％    4974  UAGCACUCAGUUAUUCUGC    71.5％

4926  UUCUAACCGAGGUCGAAAC    72.6％    4975  AUAGCACUCAGUUAUUCUG    71.4％

4927  UAACCGAGGUCGAAACGUA    72.6％    4976  AAGAAAUAGCACUCAGUUA    71.4％

4928  UCUAACCGAGGUCGAAACG    72.6％    4977  GCUGGAUCAAGUGAGCAGG    71.4％

4929  GCUGGGAAAAACACAGAUC    72.6％    4978  AAAGAAAUAGCACUCAGUU    71.4％

4930  UGCUGGGAAAAACACAGAU    72.6％    4979  CUGGAUCAAGUGAGCAGGC    71.4％

4931  UCAAGUGAGCAGGCAGCGG    72.6％    4980  AAUAGCACUCAGUUAUUCU    71.3％

4932  CAAGUGAGCAGGCAGCGGA    72.6％    4981  UGGAUCAAGUGAGCAGGCA    71.3％

4933  CUGGGAAAAACACAGAUCU    72.6％    4982  AGCACUCAGUUAUUCUGCU    71.3％

4934  UGGUAUGUGCAACAUGUGA    72.6％    4983  GAAAUAGCACUCAGUUAUU    71.3％

4935  UUGCUGGGAAAAACACAGA    72.6％    4984  AAAUAGCACUCAGUUAUUC    71.3％

4936  AGAUGUCUUUGCUGGGAAA    72.6％    4985  AAUGGCUGGAUCAAGUGAG    71.3％

4937  UUUGCUGGGAAAAACACAG    72.6％    4986  AAUGGGGAUCCAAAUAACA    71.2％

4938  UGGGAAAAACACAGAUCUU    72.5％    4987  AGAAAUAGCACUCAGUUAU    71.2％

4939  CUUUGCUGGGAAAAACACA    72.5％    4988  UGGGGAUCCAAAUAACAUG    71.2％

4940  CUGGUAUGUGCAACAUGUG    72.5％    4989  AUGGGGAUCCAAAUAACAU    71.2％

4941  CUUCUAACCGAGGUCGAAA    72.5％    4990  GGCCAAAGAAAUAGCACUC    71.1％

4942  CGAGGACUGCAGCGUAGAC    72.4％    4991  GCCAAAGAAAUAGCACUCA    71.1％

4943  GAGCGAGGACUGCAGCGUA    72.4％    4992  CCAAAGAAAUAGCACUCAG    71.1％

4944  GAGGACUGCAGCGUAGACG    72.4％    4993  CAAAGAAAUAGCACUCAGU    70.9％

4945  UGAGCGAGGACUGCAGCGU    72.3％    4994  GAAUGGGGAUCCAAAUAAC    70.9％

4946  GGUUUGUGUUCACGCUCAC    72.2％    4995  CAGGCAGCGGAGGCCAUGG    70.7％

4947  GGGUUUGUGUUCACGCUCA    72.2％    4996  AGGCAGCGGAGGCCAUGGA    70.7％

4948  CACUCAGUUAUUCUGCUGG    72.2％    4997  GUGAGCAGGCAGCGGAGGC    70.6％

4949  AAAUGGCUGGAUCAAGUGA    72.1％    4998  AUUGCUAGUCAGGCCAGGC    70.6％

4950  GCGAGGACUGCAGCGUAGA    72.1％    4999  AGUGAGCAGGCAGCGGAGG    70.6％

4951  CAAAUGGCUGGAUCAAGUG    72.1％    5000  AAGUGAGCAGGCAGCGGAG    70.6％

4952  AGUGAGCGAGGACUGCAGC    72.1％    5001  GAGCAGGCAGCGGAGGCCA    70.5％

4953  GUGAGCGAGGACUGCAGCG    72.1％    5002  GCAGGCAGCGGAGGCCAUG    70.5％

4954  ACUCAGUUAUUCUGCUGGU    72.1％    5003  AGCAGGCAGCGGAGGCCAU    70.5％

4955  AGCGAGGACUGCAGCGUAG    72.1％    5004  UGAGCAGGCAGCGGAGGCC    70.5％

4956  GUUUGUGUUCACGCUCACC    72.0％    5005  AGGACUGCAGCGUAGACGC    70.4％

4957  CAGUGAGCGAGGACUGCAG    71.9％    5006  ACAUGUGAACAGAUUGCUG    70.4％

4958  GGAUCCAAAUAACAUGGAC    71.8％    5007  CAUGUGAACAGAUUGCUGA    70.4％

4959  GGGAUCCAAAUAACAUGGA    71.8％    5008  AUGUGAACAGAUUGCUGAC    70.2％

4960  GCACUCAGUUAUUCUGCUG    71.8％    5009  GAUAUUGAAAGAUGAGCCU    70.2％

4961  UGGCCUGGUAUGUGCAACA    71.8％    5010  UAUUGAAAGAUGAGCCUUC    70.2％

4962  GGGGAUCCAAAUAACAUGG    71.8％    5011  AGAUAUUGAAAGAUGAGCC    70.2％

4963  GCCUGGUAUGUGCAACAUG    71.8％    5012  AUUGAAAGAUGAGCCUUCU    70.2％

4964  GGCCUGGUAUGUGCAACAU    71.8％    5013  AUAUUGAAAGAUGAGCCUU    70.2％

4965  CCUGGUAUGUGCAACAUGU    71.8％    5014  AUGGUUUUGGCCAGCACUA    70.2％

4966  GAGCAAAUGGCUGGAUCAA    71.6％    5015  UGGUUUUGGCCAGCACUAC    70.2％

4967  GGAGCAAAUGGCUGGAUCA    71.6％    5016  UAGAUAUUGAAAGAUGAGC    70.1％

4968  AGCAAAUGGCUGGAUCAAG    71.6％    5017  UGUGCAACAUGUGAACAGA    70.0％

4969  GCAAAUGGCUGGAUCAAGU    71.6％    5018  CGUCUUUUUUUCAAAUGCA    70.0％

4970  UGGGGCCAAAGAAAUAGCA    71.6％    5019  UGAAAAGAGGGCCUUCUAC    70.0％

4971  GGGGCCAAAGAAAUAGCAC    71.5％    5020  GUGCAACAUGUGAACAGAU    70.0％

4972  GGGCCAAAGAAAUAGCACU    71.5％

表2-8在表1-8所列甲型流感片段2(NS1&NS2)序列中以至少70％存在的保守19-mer

序列

Seq

      序列    百分比    5021  AUAACACAgUUCGAGUCUC  98.2％

ID

5022  UAACACAGUUCGAGUCUCU    98.2％    5076  AAGAUGGCUGAUUGAAGAA    91.9％

5023  UGAAUGGAAUGAUAACACA    98.0％    5077  CUAAGGGCUUUCACCGAAG    91.9％

5024  GAAUGGAAUAUUAAACAGG    98.0％    5078  AAGGGCUUUCACCGAAGAG    91.8％

5025  UGGAAUGAUAACACAAUUC    98.0％    5079  UAAGGGCUUUCACCGAAGA    91.8％

5026  AUGGAAUGAUAACACAGUG    97.9％    5080  GAUGGCUGAUUGAAGAAGU    91.7％

5027  AAUGGAAUGAUAACACAGU    97.9％    5081  AGAUGGCUGAUUGAAGAAG    91.7％

5028  UUGAAUGGAAUGAUAACAC    97.8％    5082  ACUAAGGGCUUUCACCGAA    91.4％

5029  UGAUAACACAGUUCGAGUC    97.7％    5083  UACUAAGGGCUUUCACCGA    91.3％

5030  AUGAUAACACAGUUCGAGU    97.6％    5084  AAAGCGAAUUUCAGUGUGA    91.2％

5031  GGAAUGAUAACACAGUUCG    97.6％    5085  AAGCGAAUUUCAGUGUGAU    91.0％

5032  GAAUGAUAACACAGUUCGA    97.6％    5086  GGCUUUCACCGAAGAGGGA    90.9％

5033  AAUGAUAACACAGUUCGAG    97.6％    5087  GCUUUCACCGAAGAGGGAG    90.8％

5034  CUUGAAUGGAAUGAUAACA    97.5％    5088  AUUACUAAGGGCUUUCACC    90.8％

5035  GAUAACACAGUUCGAGUCU    97.1％    5089  UUACUAAGGGCUUUCACCG    90.8％

5036  AUGUCAAAAAUGCAAUUGG    96.9％    5090  AAGAGGGAGCAAUUGUUGG    90.4％

5037  GGAUGUCAAAAAUGCAAUU    96.9％    5091  GAAGAGGGAGCAAUUGUUG    90.4％

5038  AGGAUGUCAAAAAUGCAAU    96.9％    5092  AGAGGGAGCAAUUGUUGGC    90.3％

5039  GAGGAUGUCAAAAAUGCAA    96.8％    5093  UCACCGAAGAGGGAGCAAU    90.3％

5040  GAUGUCAAAAAUGCAAUUG    96.8％    5094  UUUCACCGAAGAGGGAGCA    90.2％

5041  UGAGGAUGUCAAAAAUGCA    96.4％    5095  UUCACCGAAGAGGGAGCAA    90.2％

5042  CGGCUUCGCCGAGAUCAGA    96.2％    5096  CUUUCACCGAAGAGGGAGC    90.1％

5043  UGUCAAAAAUGCAAUUGGG    95.6％    5097  CCGAAGAGGGAGCAAUUGU    90.0％

5044  UCUACAGAGAUUCGCUUGG    95.5％    5098  ACCGAAGAGGGAGCAAUUG    90.0％

5045  GCAAUUGGGGUCCUCAUCG    94.8％    5099  CGAAGAGGGAGCAAUUGUU    90.0％

5046  CAAUUGGGGUCCUCAUCGG    94.8％    5100  CACCGAAGAGGGAGCAAUU    90.0％

5047  UGCAAUUGGGGUCCUCAUC    94.8％    5101  UUGGGGUCCUCAUCGGAGG    89.7％

5048  UCAAAAAUGCAAUUGGGGU    94.4％    5102  AUUGGGGUCCUCAUCGGAG    88.8％

5049  GUCAAAAAUGCAAUUGGGG    94.4％    5103  AAUUGGGGUCCUCAUCGGA    87.8％

5050  AAAAAUGCAAUUGGGGUCC    94.3％    5104  AUGAGGCACUUAAAAUGAC    87.7％

5051  AAAAUGCAAUUGGGGUCCU    94.3％    5105  AACACAGUUCGAGUCUCUA    87.5％

5052  AUGCAAUUGGGGUCCUCAU    94.3％    5106  ACACAGUUCGAGUCUCUAA    87.5％

5053  CAAAAAUGCAAUUGGGGUC    94.3％    5107  GAUGAGGCACUUAAAAUGA    87.3％

5054  AAAUGCAAUUGGGGUCCUC    94.3％    5108  ACAGAAACGGAAAAUGGCG    87.1％

5055  AAUGCAAUUGGGGUCCUCA    94.2％    5109  ACAGUUCGAGUCUCUAAAA    86.9％

5056  UGAAAGCGAAUUUCAGUGU    93.8％    5110  CACAGUUCGAGUCUCUAAA    86.9％

5057  UUGAUCGGCUUCGCCGAGA    93.7％    5111  AAGCAGUAAUGAGAAUGGG    86.1％

5058  CUUGAUCGGCUUCGCCGAG    93.6％    5112  UGAGGCACUUAAAAUGACC    86.0％

5059  GAAAGCGAAUUUCAGUGUG    93.6％    5113  GAAGCAGUAAUGAGAAUGG    85.8％

5060  AUCGGCUUCGCCGAGAUCA    93.4％    5114  GGUUCAUGCUAAUGCCCAA    85.8％

5061  GAUCGGCUUCGCCGAGAUC    93.4％    5115  GAGGCACUUAAAAUGACCA    85.8％

5062  UGAUCGGCUUCGCCGAGAU    93.4％    5116  AGGCACUUAAAAUGACCAU    85.8％

5063  UCGGCUUCGCCGAGAUCAG    93.2％    5117  ACUGGUUCAUGCUAAUGCC    85.7％

5064  GAGCAAUUGUUGGCGAAAU    92.8％    5118  UGGUUCAUGCUAAUGCCCA    85.7％

5065  GGAGCAAUUGUUGGCGAAA    92.8％    5119  CUGGUUCAUGCUAAUGCCC    85.5％

5066  UCCUUGAUCGGGCUUCGCC    92.7％    5120  GGCACUUAAAAUGACCAUG    85.3％

5067  UCCUUGAUCGGCUUCGCCG    92.7％    5121  UUGAAAGCGAAUUUCAGUG    85.2％

5068  GGGAGCAAUUGUUGGCGAA    92.7％    5122  GCACUUAAAAUGACCAUGG    85.2％

5069  AGGGAGCAAUUGUUGGCGA    92.5％    5123  UCAUGCUAAUGCCCAAGCA    85.1％

5070  CCUUGAUCGGCUUCGCCGA    92.4％    5124  UACAGACAUUCGCUUGGAG    84.7％

5071  GAGGGAGCAAUUGUUGGCG    92.3％    5125  UACUAUUGAGGAUGUCAAA    84.7％

5072  AGGGCUUUCACCGAAGAGG    92.3％    5126  ACAGAGAUUCGCUUGGAGA    84.7％

5073  GGGCUUUCACCGAAGAGGG    92.2％    5127  CAUACUAUUGAGGAUGUCA    84.7％

5074  AUAGAUGGCUGAUUGUAAG    92.1％    5128  GUUCAUGCUAAUGCCCAAG    84.7％

5075  UAAGAUGGCUGAUUGAAGA    92.1％    5129  AUACUAUUGAGGAUGUCAA    84.7％

5130  UUCAUGCUAAUGCCCAAGC    84.7％    5184  CAUCAUGUUGAAAGCGAAU    81.3％

5131  UGGCUGAUUGAAGAAGUGA    84.7％    5185  AUGCCCCAUUCCUUGAUCG    81.3％

5132  GGCUGAUUGAAGAAGUGAG    84.7％    5186  GAUGCCCCAUUCCUUGAUC    81.3％

5133  ACUAUUGAGGAUGUCAAAA    84.6％    5187  GGCGAAAUCUCACCAUUGC    81.2％

5134  ACAUACUAUUGAGGAUGUC    84.5％    5188  UUGUUGGCGAAAUCUCACC    81.1％

5135  CAGAGAUUCGCUUGGAGAA    84.5％    5189  UUGGCGAAAUCUCACCAUU    81.0％

5136  UUCCAGGACAUACUAUUGA    84.4％    5190  AGAAACGGAAAAUGGCGAG    81.0％

5137  UUGAGGAUGUCAAAAAUGC    84.4％    5191  UGUUGGCGAAAUCUCACCA    81.0％

5138  CAGGACAUACUAUUGAGGA    84.4％    5192  UGAUUGAAGAAGUGAGACA    81.0％

5139  GGACAUACUAUUGAGGAUG    84.4％    5193  GAAACGGAAAAUGGCGAGA    80.9％

5140  AGGACAUACUAUUUGAGAU    84.4％    5194  UGGCGAAAUCUCACCAUUG    80.9％

5141  CCAGGACAUACUAUUGAGG    84.4％    5195  CCAAAACAGAACGGAAAAA    80.9％

5142  GACAUACUAUUUGAGAUGU    84.4％    5196  AUUGUUGGCGAAAUCUCAC    80.9％

5143  UCCAGGACAUACUAUUGAG    84.4％    5197  AAUUGUUGGCGAAAUCUCA    80.9％

5144  AUGGCUGAUUGAAGAAGUG    84.3％    5198  UGACUAUUGAGGAAUUGUC    80.9％

5145  CUAUUGAGGAUGUCAAAAA    84.2％    5199  GUUGGCGAAAUCUCACCAU    80.9％

5146  AUUGAGGAUGUCAAAAAUG    84.2％    5200  CUAUUGAGGAAUUGUCAAG    80.8％

5147  UAUUGAGGAUGUCAAAAAU    84.2％    5201  ACUAUUGAGGAAUUGUCAA    80.8％

5148  UAUUACUAAGGGCUUUCAC    84.1％    5202  CAGAAACGGAAAAUGGCGA    80.8％

5149  CCAUUCCUUGAUCGGCUUC    84.0％    5203  GACUAUUGAGGAAUUGUCA    80.8％

5150  AUUCCUUGAUCGGCUUCGC    83.8％    5204  ACAUCAUGUUGAAAGCGAA    80.7％

5151  GAGAUUCGCUUGGAGAAGC    83.8％    5205  CCCCAUUCCUUGAUCGGCU    80.7％

5152  AGAGAUUCGCUUGGAGAAG    83.8％    5206  ACGGAAAAUGGCGAGAACA    80.5％

5153  CAUUCCUUGAUCGGCUUCG    83.8％    5207  UGCCCCAUUCCUUGAUCGG    80.5％

5154  CUACAGAGAUUCGCUUGGA    83.7％    5208  AACGGAAAAUGGCGAGAAC    80.5％

5155  AGAUUCGCUUGGAGAAGCA    83.4％    5209  GCCCCAUUCCUUGAUCGGC    80.4％

5156  AUUCGCUUGGAGAAGCAGU    83.0％    5210  AUGACUAUUGAGGAAUUGU    80.4％

5157  GUGAUGCCCCAUUCCUUGA    83.0％    5211  AAAUCUCACCAUUGCCUUC    80.4％

5158  GAUUCGCUUGGAGAAGCAG    83.0％    5212  AAACGGAAAAUGCCGAGAA    80.4％

5159  UUGGAGAAGCAGUAAUGAG    82.7％    5213  GAAAUCUCACCAUUGCCUU    80.4％

5160  CUUGGAGAAGCAGUAAUGA    82.7％    5214  CGAAAUCUCACCAUUGCCU    80.3％

5161  GAAGAGAUAAGAUGGCUGA    82.1％    5215  AACAUCAUGUUGAAAGCGA    80.3％

5162  AAGAGAUAAGAUGGCUGAU    82.1％    5216  GCAAUUGUUGGCGAAAUCU    80.3％

5163  AGAUAAGAUGGCUGAUUGA    82.0％    5217  CAAUUGUUGGCGAAAUCUC    80.2％

5164  GAUAAGAUGGCUGAUUGAA    81.9％    5218  GCGAAAUCUCACCAUUGCC    80.2％

5165  GUUGAAAGCGAAUUUCAGU    81.9％    5219  CCCAUUCCUUGAUCGGCUU    80.2％

5166  GCUUGGAGAAGCAGUAAUG    81.9％    5220  AUUGAAGAAGUGAGACACA    80.1％

5167  UGGAGAAGCAGUAAUGAGA    81.9％    5221  AAUCUCACCAUUGCCUUCU    80.0％

5168  GAGAUAAGAUGGCUGAUUG    81.9％    5222  AACAGAAACGGAAAAUGGC    80.0％

5169  UUCGCUUGGAGAAGCAGUA    81.9％    5223  UGAUGCCCCAUUCCUUGAU    80.0％

5170  AGAGAUAAGAGGCUGAAUU    81.8％    5224  GCUGAUUGAAGAAGUGAGA    79.6％

5171  UCGCUUGGAGAAGCAGUAA    81.7％    5225  CUGAUUGAAGAAGUGAGAC    79.6％

5172  CGCUUGGAGAAGCAGUAAU    81.7％    5226  UUCUUUUCCAGGACAUACU    79.3％

5173  CAUGUUGAAAGCGAAUUUC    81.6％    5227  ACUCCAAAACAGAAACGGA    79.3％

5174  UCAUGUUGAAAGCGAAUUU    81.6％    5228  UCCCUAAGGGGAAGAGGCA    79.3％

5175  UGUUGAAAGCGAAUUUCAG    81.6％    5229  AGCAAUUGUUGGCGAAAUC    79.1％

5176  UAACUGACAUGACUAUUGA    81.6％    5230  UCUUUUCCAGGACAUACUA    79.1％

5177  AUGUUGAAAGCGAAUUUCA    81.6％    5231  GAUUGAAGAAGUGAGACAC    78.8％

5178  CAAAACAGAAACGGAAAAU    81.5％    5232  AUUCCAACACUGUGUCAAG    78.6％

5179  AAAACAGAAACGGAAAAUG    81.5％    5233  CUUCUUUUCCAGGACAUAC    78.5％

5180  AAACAGAAACGGAAAAUGG    81.5％    5234  ACCAUUGCCUUCUUUUCCA    78.5％

5181  UCCAAAACAGAAACGGAAA    81.5％    5235  CCAUUGCCUUCUUUUCCAG    78.5％

5182  CUCCAAAACAGAAACGGAA    81.4％    5236  CAUUGCCUUCUUUUCCAGG    78.4％

5183  AUCAUGUUGAAAGCGAAUU    81.4％    5237  CCUUCUUUUCCAGGACAUA    78.4％

5238  GCCUUCUUUUUCCAGACAU    78.4％    5292  CCAACACUGUGUCAAGUUU    75.3％

5239  UGCCUUCUUUUCCAGGACA    78.4％    5293  AGAAGCAGUAAUGAGAAUG    75.3％

5240  CACCAUUGCCUUCUUUUCC    78.3％    5294  AGUGGAACAGGAGAUAAGA    75.3％

5241  UUGCCUUCUUUUCCAGGAC    78.3％    5295  CUUACUCCAAAACAGAAAC    75.2％

5242  UGGAUUCCAACACUGUGUC    78.3％    5296  CUCACCAUUGCCUUCUUUU    75.1％

5243  AUGGAUUCCAACACUGUGU    78.3％    5297  UCUCACCAUUGCCUUCUUU    75.1％

5244  UCACCAUUGCCUUCUUUUC    78.3％    5298  AUCUCACCAUUGCCUUCUU    75.1％

5245  GGAUUCCAACACUGUGUCA    78.3％    5299  UCCAACACUGUGUCAAGUU    75.0％

5246  AUUGCCUUCUUUUCCAGGA    78.2％    5300  UACUCCAAAACAGAAACGG    74.8％

5247  GAUUCCAACACUGUGUCAA    78.2％    5301  UUACUCCAAAACAGAAACG    74.8％

5248  UUGAAGAAGUGAGACACAG    77.8％    5302  UUCCAACACUGUGUCAAGU    74.7％

5249  UUGAAGUGGAACAGGAGAU    77.7％    5303  AUCAGAAUGGACCAGGCAA    74.5％

5250  UUUGAAGUGGAACAGGAGA    77.7％    5304  UAAUGAGAAUGGGGGACCU    74.0％

5251  UGAAGAAGUGAGACACAGA    77.2％    5305  UAAUGGAUUCCAACACUGU    74.0％

5252  CUGACAUGACUAUUGAGGA    77.2％    5306  CAAGUUUCCAGGUAGAUUG    74.0％

5253  UGACAUGACUAUUGAGGAA    77.2％    5307  CAUAAUGGAUUCCAACACU    73.9％

5254  CAAAUAACAUUCAUGCAAG    77.0％    5308  CAGUAAUGAGAAUGGGGGA    73.9％

5255  AAAUAACAUUCAUGCAAGC    77.0％    5309  GCAGUAAUGAGAAUGGGGG    73.9％

5256  ACUGACAUGACUAUUGAGG    77.0％    5310  UCAAGUUUCCAGGUAGAUU    73.9％

5257  CUUUUCCAGGACAUACUAU    76.9％    5311  AAUGGAUUCCAACACUGUG    73.％

5258  UUUUCCAGGACAUACUAUU    76.9％    5312  ACAUAAUGGAUUCCAACAC    73.9％

5259  UUUCCAGGACAUACUAUUG    76.8％    5313  AGUAAUGAGAAUGGGGGAC    73.8％

5260  AAACAAGUUGUAGACCAAG    76.8％    5314  AAUGAGAAUGGGGGACCUC    73.8％

5261  ACAAGUUGUAGACCAAGAA    76.7％    5315  GUAAUGAGAAUGGGGGACC    73.7％

5262  AAGUUGUAGACCAAGAACU    76.7％    5316  AGCAGUAAUGAGAAUGGGG    73.7％

5263  AACAAGUUGUAGACCAAGA    76.7％    5317  UGUCAAGUUUCCAGGUAGA    73.7％

5264  GAAUCUGAUGAGGCACUUA    76.7％    5318  CCACACCUGCUUCGCGAUA    73.6％

5265  AGAAUCUGAUGAGGCACUU    76.6％    5319  UCCACACCUGCUUCGCGAU    73.6％

5266  AACUGACAUGACUAUUGAG    76.5％    5320  ACAUGACUAUUGAGGAAUU    73.6％

5267  AAUCUGAUGAGGCACUUAA    76.5％    5321  CUCCACACCUGCUUCGCGA    73.6％

5268  UCUGAUGAGGCACUUAAAA    76.5％    5322  CACACCUGCUUCGCGAUAC    73.6％

5269  UGAUGAGGCACUUAAAAUG    76.5％    5323  UGUGUCAAGUUUCCAGGUA    73.6％

5270  CUGAUGAGGCCACUAAAAU    76.5％    5324  GACAUGACUAUUGAGGAAU    73.6％

5271  CAAGUUGUAGACCAAGAAC    76.5％    5325  GUGUCAAGUUUCCAGGUAG    73.6％

5272  CCACCCAUGUUGGAAAGCA    76.2％    5326  ACUGUGUCAAGUUUCCAGG    73.5％

5273  AUCUGAUGAGGCACUUAAA    76.2％    5327  CUGUGUCAAGUUUCCAGGU    73.5％

5274  AGCCACCCAUGUUGGAAAG    76.2％    5328  AUAAUGGAUUCCAACACUG    73.5％

5275  GCCACCCAUGUUGGAAAGC    76.2％    5329  GUCAAGUUUCCAGUAGAU     73.5％

5276  CAGCCACCCAUGUUGGAAA    76.2％    5330  CACCUGCUUCGCGAUACAU    73.5％

5277  GAAGUGGAACAGGAGAUAA    76.0％    5331  ACACCUGCUUCGCGAUACA    73.4％

5278  AAGUGGAACAGGAGAUAAG    75.9％    5332  CAUCAGAAUGGACCAGGCA    73.4％

5279  UGAAGUGGAACAGGAGAUA    75.8％    5333  GGCUUCGCCGAGAUCAGAG    73.4％

5280  AGGAGAUAAGAACUUUCUC    75.8％    5334  GCAUCAGAAUGGACCAGGC    73.3％

5281  GAACAGGAGAUAAGAACUU    75.8％    5335  GCUUCGCGAUACAUAACUG    73.3％

5282  CAGGAGAUAAGAACUUUCU    75.8％    5336  CACUGUGUCAAGUUUCCAG    73.3％

5283  ACAGGAGAUAAGAACUUUC    75.7％    5337  ACACUGUGUCAAGUUUCCA    73.3％

5284  AACAGGAGAUAAGAACUUU    75.7％    5338  AACACUGUGUCAAGUUUCC    73.3％

5285  GUGGAACAGGAGAUAAGAA    75.6％    5339  CUUCGCGAUACAUAACUGA    73.3％

5286  UGGAACAGGAGAUAAGAAC    75.6％    5340  UGGACCAGGCAAUCAUGGA    73.2％

5287  GGAACAGGAGAUAAGAACU    75.6％    5341  CGGAAAAUGGCGAGAACAG    73.2％

5288  GGAGAAGCAGUAAUGAGAA    75.6％    5342  AAUGGCGAGAACAGCUAGG    73.2％

5289  GUCCCUAAGGGGAAGAGGC    75.4％    5343  CCUGCUUCGCGAUACAUAA    73.2％

5290  ACUUACUCCAAAACAGAAA    75.4％    5344  UGCAUCAGAAUGGACCAGG    73.2％

5291  GAGAAGCAGUAAUGAGAAU    75.3％    5345  UGCUUCGCGAUACAUAACU    73.2％

5346  CUGCUUCGCGAUACAUAAC    73.2％    5400  GGGACCUCCACUUACUCCA    71.3％

5347  UGGCGAGAAUAGCUAGGUC    73.1％    5401  GGGGGACCUCCACUUACUC    71.3％

5348  ACCUGCUUCGCGAUACAUA    73.1％    5402  AAAACAUCAUGUUGAAAGC    71.3％

5349  AUGGCGAGAACAGCUAGGU    73.1％    5403  AGUCUCUUAAAUUCUACAG    71.2％

5350  AAAUGGCGAGAACAGCUAG    73.1％    5404  AAAUCUACAGAGAUUCGCU    71.2％

5351  UAUUGAGGAAUUGUCAAGA    73.0％    5405  UGGAGAAAAACAUCAUGUU    71.2％

5352  AUGGACCAGGCAAUCAUGG    73.0％    5406  AAAAUCUACAGAGAUUCGC    71.2％

5353  UCAGAAUGGAACAGGCAAU    72.9％    5407  GUCUCUAAAAUUCUACAGA    71.2％

5354  GCGAGAACAGCUAGGUCAA    72.8％    5408  AAAAACAUCAUGUUGAAAG    71.2％

5355  GAGAACAGCUAGGUCAAAA    72.8％    5409  GGACCAGGCAAUCAUGGAG    71.2％

5356  CGAGAACAGCCAGGUCAAA    72.8％    5410  CAUGGAGAAAAACAUCAUG    71.2％

5357  GGCGAGAACAGCUAGGUCA    72.8％    5411  UCUAAAAAUCUACAGAGAU    71.1％

5358  AAUGGACCAGGCAAUCAUG    72.7％    5412  ACCAGGCAAUCAUGGAGAA    71.1％

5359  AAGCAGCCACCCAUGUUGG    72.7％    5413  CUCUAAAAAUCUACAGAGA    71.1％

5360  GAAUGGACCAGGCAAUCAU    72.6％    5414  CGAGUCUCUAAAAAUCUAC    71.1％

5361  UCAAGAAACUGGUUCAUGC    72.6％    5415  CUGUUUGAAGUGGAACAGG    71.1％

5362  GCAGCCACCCAUGUUGGAA    72.6％    5416  AGAAAAACAUCAUGUUGAA    71.1％

5363  AGCAGCCACCCAUGUUGGA    72.6％    5417  CUAAAAAUCUACAGAGAUU    71.1％

5364  CAAGAAACUGGUUCAUGCU    72.6％    5418  GAGAAAAACAUCAUGUUGA    71.1％

5365  GACCUCCACUUACUCCAAA    72.5％    5419  UGAGGAAUUGUCAAGAAAC    71.1％

5366  AACUGGUUCAUGCUAAUGC    72.5％    5420  GAAAAACAUCAUGUUGAAA    71.1％

5367  AGAAUGGACCAGGCAAUCA    72.5％    5421  AUGGAGAAAAACAUCAUGU    71.1％

5368  CACUUACUCCAAAACAGAA    72.5％    5422  UGUUUGAAGUGGAACAGGA    71.1％

5369  UCCACUUACUCCAAAACAG    72.4％    5423  UUCGAGUCUCUAAAAAUCU    71.1％

5370  CAGAAUGGACCAGGCAAUC    72.4％    5424  UCGAGUCUCUAAAAAUCUA    71.1％

5371  CCACUUACUCCAAAACAGA    72.3％    5425  UUGAGGAAUUGUCAAGAAA    71.1％

5372  GAAACUGGUUCAUGCUAAU    72.3％    5426  GGAAUUGUCAAGAAACUGG    71.1％

5373  AGAAACUGGUUCAUGCUAA    72.3％    5427  GUUCGAGUCUCUAAAAAUC    71.1％

5374  AAACUGGUUCAUGCUAAUG    72.3％    5428  GACCAGGCAAUCAUGGAGA    71.1％

5375  CUCCACUUACUCCAAAACA    72.3％    5429  AGGAAUUGUCAAGAAACUG    71.1％

5376  CAUGACUAUUGAGGAAUUG    72.2％    5430  GAGUCUCUAAAAAUCUACA    71.1％

5377  AAGAAACUGGUUCAUGCUA    72.2％    5431  UCUCUAAAAAUCUACAGAG    71.1％

5378  CAGGUAGAUUGCUUUUUUU    72.1％    5432  GGAGAAAAACAUCAUGUUG    71.1％

5379  CCUCCACUUACUCCAAAAC    72.1％    5433  GAGGAAUUGUCAAGAAACU    71.1％

5380  ACCUCCACUUACUCCAAAA    72.1％    5434  AAUUGUCAAGAAACUGGUU    71.0％

5381  AGGUAGAUUGCUUUCUUUG    72.1％    5435  CAAAGACAUAAUGGAUUCC    71.0％

5382  GGUAGAUUGCUUUCUUUGG    72.1％    5436  GAAUUGUCAAGAAACUGGU    71.0％

5383  UAGAUUGCUUUCUUUGGCA    72.0％    5437  UGUCAAGAAACUGGUUCAU    71.0％

5384  GUAGAUUGCUUUCUUUGGC    72.0％    5438  UGAGAAUGGGGGACCUCCA    71.0％

5385  CAACACUGUGUCAACUUUC    71.9％    5439  AUGAGAAUGGGGGACCUCC    71.0％

5386  AGAUUGCUUUCUUUGGCAU    71.9％    5440  UGCUGUUUGAAGUGGAACA    71.0％

5387  AACAGCUAGGUCAAAAGUU    71.8％    5441  GUCAAGAAACUGGUUCAUG    71.0％

5388  AAUCUACAGAGAUUCGCUU    71.8％    5442  CUGCUGUUUGAAGUGGAAC    71.0％

5389  GAACAGCUAGGUCAAAAGU    71.8％    5443  UUCCAGGUAGAUUGCUUUC    70.9％

5390  AUCUACAGAGAUUCGCUUG    71.7％    5444  GGACCUCCACUUACUCCAA    70.9％

5391  AGUUUCCAGGUAGAUUGCU    71.6％    5445  CCAGGUUAGAUUGCUUCUU    70.9％

5392  GUUUCCAGGUAGAUUGCUU    71.6％    5446  AUUGAGGAAUUGUCAAGAA    70.9％

5393  AAGUUUCCAGGUAGAUUGC    71.5％    5447  AUUGUCAAGAAACUGGUUC    70.9％

5394  AGAACAGCUAGGUCAAAAG    71.5％    5448  UUGUCAAGAAACUGGUUCA    70.9％

5395  UGGGGGACCUCCACUUACU    71.5％    5449  UAAAAAUCUACAGAGAUUC    70.9％

5396  AUGGGGGAGCUCCACUUAC    71.4％    5450  UCCAGGUAGAUUGCUUUCU    70.9％

5397  AGUUCGAGUCUCUAAAAAU    71.3％    5451  AGUUUUGAGCAAAUAACAU    70.8％

5398  GGGGACCUCCACUUACUCC    71.3％    5452  GCUGUUUGAAGUGGAACAG    70.8％

5399  CAGUUCGAGUCUCUAAAAA    71.3％    5453  CAGGCAAUCAUGGAGAAAA    70.7％

5454  AAUAGUUUUGAGCAAAUAA    70.7％    5469  GAAUGGGGGACCUCCACUU    70.2％

5455  UUUCCAGGUUAGAUUCUUU    70.7％    5470  CAAUCAUGGAGAAAAACAU    70.1％

5456  AGAAUGGGGGACCUCCACU    70.7％    5471  AAUCAUGGAGAAAAACAUC    70.1％

5457  AAACAUCAUGUUGAAAGCG    70.7％    5472  GGCAAUCAUGGAGAAAAAC    70.1％

5458  GAGAAUGGGGGACCUCCAC    70.7％    5473  GCAAUCAUGGAGAAAAACA    70.1％

5459  GUUUUGAGCAAAUAACAUU    70.7％    5474  UUUGCAUCAGAAUGGACCA    70.1％

5460  AAAAAUCUACAGAGAUUCG    70.6％    5475  UUGCAUCAGAAUGGACCAG    70.1％

5461  UAGUAUUACUAAGGGCUUU    70.6％    5476  CUCUCGGUCUAGACAUCAA    70.1％

5462  AUAGUUUUGAGCAAAUAAC    70.6％    5477  UCUCGGUCUAGACAUCAAA    70.1％

5463  GUAUUACUAAGGGCUUUCA    70.5％    5478  AAUGGGGGACCUCCACUUA    70.1％

5464  UAGUUUUGAGCAAAUAACA    70.5％    5479  AUCAUGGAGAAAAACAUCA    70.1％

5465  AGUAUUACUAAGGGCUUUC    70.5％    5480  CUUUGCAUCAGAAUUGGAC    70.0％

5466  CCAGGCAAUCAUGGAGAAA    70A％     5481  CCGAGAUCAGAGGUCCCUA    70.0％

5467  AGGCAAUCAUGGAGAAAAA    70.2％    5482  GUUUGAAGUGGAACAGGAG    70.0％

5468  ACUCUCGGUCUAGACAUCA    70.2％    5483  CGAGAUCAGAGGUCCCUAA    70.0％

我们的研究表明，RNAi机制可耐受靶RNA与siRNA双链体反义引导序列之间的小量错配。因此，靶向流感中高度保守位点的单个siRNA双链体对相对于高度保守位点仅具有一个或几个错配的小变体种类通常仍将有活性。我们已经使用此观察结果来扩展可被所给siRNA双链体靶向的甲型流感病毒序列变体的列表。

表3中从试验筛选研究鉴别的前九个siRNA已经从表20中提取出。

表3：从试验筛选研究鉴别的前九个siRNA位点，显示了在表20-1至20-6所界定甲型流感的保守和小变体19-mer序列。

Seq    Ref

              片段    匹配序列               总数％

ID     ID

7      7      PB2     AGACAGCGACCAAAAGAAU    99.1％

5503   7              AGACAGCGACCAAAAGgAU    0.3％

5504   7              AGACAGCGACCAAAgGAAU    0.1％

5505   7              AGACAGCGACCAAAAGAuU    0.1％

5506   7              AGACgaCGAUCAAAAGAAU    0.1％

17     17     PB2     ACUGACAGCCAGACAGCGA    99.0％

5543   17             ACUGACAGuCAGACAGCGA    0.2％

5544   17             ACUGAUAGCCAGACAGCGA    0.3％

5545   17             ACCGACAGCCAGACAGCGA    0.2％

5546   17             ACUGACAGCCAGACgaCGA    0.1％

48     48     PB2     CGGGACUCUAGCAUACUUA    98.0％

5726   48             CGGGACUCUAGCAUgCUUA    0.1％

5727   48             CGGGACUuUAGCAUACUUA    0.2％

5728   48             aGGGACUCUAGCAUACUUA    0.1％

5729  48               CGaGACUCUAGCAUACUUA    0.4％

5730  48               CGGaACUCUAGCAUACUUA    0.6％

5731  48               CGGGACUaUAGCAUACUUA    0.1％

5732  48               CGGGACUCcAGCAUACUUA    0.3％

5733  48               CGGGACUCUAaCAUACUUA    0.1％

1187  1187  PBI        GAUUCUGUUCCACCAUGAA    90.9％

6265  1187             GAUCUGUUuCACCAUUGAA    0.7％

6266  1187             aAUCUGUUCCACCAUUGAA    0.1％

6267  1187             GAcCUGUUCCACCUUUGAA    6.9％

6268  1187             GAUCUGcUCCACCAUUGAA    0.2％

6269  1187             GAUGUGUUaCACCAUUGAA    0.1％

6270  1187             GAUCUGUUCCACCAUUaAA    0.1％

6271  1187             GAcCUGUUCuACCAUUGAA    0.1％

6272  1187             GAcCUGcUCCACCAUUGAA    0.3％

1206  1206  PB1        AUGAAGAUCUGUUCCACCA    88.6％

6467  1206             AUGAAGAUCUGUUUCACCA    0.7％

6468  1206             AUGAgGAUCUGUUCCACCA    0.2％

6469  1206             AcGAAGAUCUGUUCCACCA    0.1％

6470  1206             AUGAAaAUCUGUUCCACCA    0.1％

6471  1206             AUGAAGAcCUGUUCCACCA    6.8％

6472  1206             AUGAAGAUCUGcUCCACCA    0.2％

6473  1206             AUGAAGAUCUGUUaCACCA    0.1％

6474  1206             cUGAGGAUCUGUUCCACCA    0.1％

6475  1206             uUGAAGAUCUGUUCCACCA    2.0％

6476  1206             AUGAAGAcCUGUUCuACCA    0.1％

6477  1206             AUaAAGAcCUGUUCCACCA    0.1％

6478  1206             AUGAAGAcCUGcUCCACCA    0.2％

2393  2393  PA         UUGAGGAGUGCCUGAUUAA    98.7％

6888  2393             UUGAGGAGUGCCUGgUUAA    0.1％

6889  2393             UUGAGGAaUGCCUGAUUAA    1.0％

6890  2393             UUGAGGAGUGCCUaAUUAA    0.2％

2394  2394  PA         GCAAUUGAGGAGUGCCUGA    98.6％

6891  2394             GCAAUUGAGGAGUGCCUGg    0.1％

6892  2394             GCAgUUGAGGAGUGCCUGA    0.1％

6893  2394             GCAAUUGAGGAaUUCCUGA    1.0％

6894  2394             GCAAUUGAGGAGUGCCUaA    0.2％

3560  3560  NP         GAUCUUAUUUCUUCGGAGA    96.0％

8041  3560             GAUCCUAUUUCUUCGGgGA    1.7％

8042  3560             GAUCUUAUUUCUUuGGAGA    0.2％

8043  3560             GgUCUUAUUUCUUCGGAGA    0.9％

8044  3560             GuUCUUAUUUCUUCGGAGA    1.1％

3561  3561  NP         GGAUCUUAUUUCUUCGGAG    96.0％

8045  3561             GGAUCUUAUUUCUUCGGgG    1.7％

8046  3561             GGAUCUUAUUUCDUuGGAG    0.2％

8047  3561             GGgUCUUAUUUCUUCGGAG    0.9％

8048  3561             GGuUCUUAUUUCUUCGGAG    1.1％

使用Madin-Darby犬肾细胞(MDCK)。对于电穿孔，将细胞保持在无血清的RPMI 1640培养基。在感染培养基中进行病毒感染。使用甲型流感病毒/PR/8/34(PR8)和A/WSN/33(WSN)，H1N1亚型。测试的有义链和反义链列于表4。

表4 siRNA序列

名称	siRNA序列    (5’-3’)
			PB2-2210/2230(有义)	ggagacgugguguugguaadTdT	(SEQ ID NO：10710)
PB2-2210/2230(反义)	uuaccaacaccacgucuccdTdT	(SEQ ID NO：10711)
			PB2-2240/2260(有义)	cgggacucuagcauacuuadTdT	(SEQ ID NO：10712)
PB2-2240/2260(反义)	uaaguaugcuagagucccgdTdT	(SEQ ID NO：10713)
			PB1-6/26(有义)	gcaggcaaaccauuugaaudTdT	(SEQ ID NO：10714)
PB1-6/26(反义)	auucaaaugguuugccugcdTdT	(SEQ ID NO：10715)
			PB1-129/149(有义)	caggauacaccauggauacdTdT	(SEQ ID NO：10716)
PB1-129/149(反义)	guauccaugguguauccugdTdT	(SEQ ID NO：10717)
			PB1-2257/2277(有义)	gaucuguuccaccauugaadTdT	(SEQ ID NO：10718)
PB1-2257/2277(反义)	uucaaugguggaacagaucdTdT	(SEQ ID NO：10719)
			PA-44/64(有义)	ugcuucaauccgaugauugdTdT	(SEQ ID NO：10720)
PA-44/64(反义)	caaucaucggauugaagcadTdT	(SEQ ID NO：10721)
			PA-739/759(有义)	cggcuacauugagggcaagdTdT	(SEQ ID NO：10722)
PA-739/759(反义)	cuugcccucaauguagccgdTdT	(SEQ ID NO：10723)
			PA-2087/2107(G)(有义)	gcaauugaggagugccugadTdT	(SEQ ID NO：10724)
PA-2087/2107(G)(反义)	ucaggcacuccucaauugcdTdT	(SEQ ID NO：10725)
			PA-2110/2130(有义)	ugaucccuggguuuugcuudTdT	(SEQ ID NO：10726)
PA-2110/2130(反义)	aagcaaaacccagggaucadTdT	(SEQ ID NO：10727)
			PA-2131/2151(有义)	ugcuucuugguugaacuccdTdT	(SEQ ID NO：10728)
PA-2131/2151(反义)	ggaguugaaccaagaagcadTdT	(SEQ ID NO：10729)
			NP-231/251(有义)	uagagagaauggugcucucdTdT	(SEQ ID NO：10730)
NP-231/251(反义)	gagagcaccauucucucuadTdT	(SEQ ID NO：10731)
			NP-390/410(有义)	uaaggcgaaucuggcgccadTdT	(SEQ ID NO：10732)
NP-390/410(反义)	uggcgccagauucgccuuadTdT	(SEQ ID NO：10733)
			NP-1496/1516(有义)	ggaucuuauuucuucggagdTdT	(SEQ ID NO：10734)
NP-1496/1516(反义)	cuccgaagaaauaagauccdTdT	(SEQ ID NO：10735)
			NP-1496/1516a(有义)	ggaucuuauuucaucggagadTdT	(SEQ ID NO：10736)
NP-1496/1516a (反义)	ucAuccgaagaaauaagauccdTdT	(SEQ ID NO：10737)
			M-37/57(有义)	ccgaggucgaaacguacgudTdT	(SEQ ID NO：10738)
M-37/57(反义)	acguacguuucgaccucggdTdT	(SEQ ID NO：10739)
			M-480/500(有义)	cagauugcugacucccagcdTdT	(SEQ ID NO：10740)
M-480/500(反义)	gcugggagucagcaaucugdTdT	(SEQ ID NO：10741)
			M-598/618(有义)	uggcuggaucgagugagcadTdT	(SEQ ID NO：10742)
M-598/618(反义)	uggucacucgauccagccadTdT	(SEQ ID NO：10743)
			M-934/954(有义)	gaauaucgaaaggaacagcdTdT	(SEQ ID NO：10744)

M-934/954(反义)	gcuguuccuuucgauauucdTdT	(SEQ ID NO：10745)
			NS-128/148(有义)	cggcuucgccgagaucagadAdT	(SEQ ID NO：10746)
NS-128/118(反义)	ucugaucucggcgaagccgdAdT	(SEQ ID NO：10747)
			NS-562/582(R)(有义)	guccuccgaugaggacuccdTdT	(SEQ ID NO：10748)
NS-562/582(R)(反义)	ggaguccucaucggaggacdTdT	(SEQ ID NO：10749)
			NS-589/609(有义)	ugauaacacaguucgagucdTdT	(SEQ ID NO：10750)
NS-589/609(反义)	gacucgaacuguguuaucadTdT	(SEQ ID NO：10751)

所有siRNA都由Dharmacon Research (Lafayette，CO)使用2’ACE保护化学法合成并经由电穿孔转染入细胞。电穿孔6至8小时后，洗去含有血清的培养基，以合适的多重感染的PR8或WSN病毒接种于细胞。以1,000PFU(每1,000细胞一个病毒；MOI＝0.001)或10,000 PFU(每100细胞一个病毒；MOI＝0.01)的病毒感染细胞。在室温培养1小时后，带有4μg/ml胰蛋白酶的2ml感染培养基加至每孔，培养细胞，并在所指示的时间从受感染培养物收集上清液，经由鸡红细胞血凝而确定病毒滴度。

感染后24、36、48和60小时收集上清液。使用如Knipe DM，HoWley，PM，Fundamental Virology，第4版，p.34-35所述的标准血凝素试验来测量病毒滴度。在V-底的96孔板中进行血凝素试验。每个样品的系列2倍稀释物在冰上培养1小时，伴有等量体积的0.5％鸡红细胞悬浮液(CharlesRiver Laboratories)。含有粘附、均匀层红细胞的孔记录为阳性。对噬菌斑检测，每个样品的系列10倍稀释物对病毒滴定，如本领域已知的如Fundamental Virology，第4版，p.32所述的。

为了研究使用siRNA抑制流感病毒复制的可行性，靶向各种甲型流感病毒RNA。尤其是，使用易于感染并广泛用于研究流感病毒的MDCK细胞系。

每种siRNA分别通过电穿孔引入MDCK细胞群体。使用靶向于GFP(有义：5’-GGCUACGUCCAGGAGCGCAUU-3’(SEQ ID NO：10752)；反义：5’-UGCGCUCCUGGACGUAGCCUU-3’(SEQ ID NO：10753))的siRNA作为对照。该siRNA是指GFP-949。在随后的实验中(在以下实施例中描述)，在两条链的3’端的UU突出端被dTdT代替而不影响效果。进行模拟电穿孔作为对照。电穿孔8小时后，以甲型流感病毒PR8或WSN以0.1或0.01的MOI感染细胞，并分析在各时间点(24、36、48、60小时)的病毒产生，此后使用标准血凝素检测。使用标准方法以流式细胞计检测GFP表达。

图11A和11B比较了通过测量HA滴度而确定单独siRNA抑制甲型流感病毒毒株A/Puerto Rico/8/34(H1N1)(图11A)或甲型流感病毒毒株A/WSN/33(H1N1)(图11B)能力的实验结果。因此高HA滴度表示缺少抑制而低HA滴度表示有效抑制。以0.01的MOI感染MDCK细胞。对这些实验，检测了靶向PB1片段(PB1-2257/2277)的一种siRNA，靶向PB2片段(PB2-2240/2260)的一种siRNA，靶向PA片段(PA-2087/2107(G))的一种siRNA，靶向NP基因组和转录子(NP-231/251、NP-390/410、NP-1496/1516)的三种不同siRNA。注意图11A和11B的图例只列出了siRNA的5’核苷酸。

图11A和11B中的符号如下：填充方块代表未接受siRNA的对照细胞。空白方块代表接受GFP对照siRNA的细胞。填充圆圈代表接受siRNAPB1-2257/2277的细胞。空白圆圈代表接受siRNA PB2-2240/2260的细胞。空白三角代表接受siRNA PA-2087/2107(G)的细胞。X符号代表接受siRNANP-231/251的细胞。+代表接受siRNA NP-390/410的细胞。填充三角代表接受siRNA NP-1496/1516的细胞。注意到图中有些符号有时是重叠的。例如，图11B中空白三角和填充三角是重合的。

不存在siRNA(模拟TF)或存在对照(GFP)siRNA时，病毒滴度随时间增加，在感染后约48-60小时到达峰值。相反，存在任何siRNA时，在60小时病毒滴度显著降低。例如，在毒株WSN中HA滴度(反映病毒水平)当siRNA PB2-2240或NP-231存在时是对照中的大约一半。尤其是，在两种毒株中当存在siRNA NP-1496时病毒水平低于检测限(10,000PFU/ml)。这表示在PR8毒株中超过60倍的减少和WSN毒株中超过120倍的减少。当WSN毒株中存在siRNAPA-2087(G)时，病毒水平也低于检测限(10,000 PFU/ml)，并且在毒株PR8中尤其低。甚至从早期测量时间点，siRNA对病毒繁殖的抑制也很明显。在感染后72小时的时间点已经观察到有效抑制，包括病毒繁殖抑制到不可检测的水平(如由HA滴度确定的)。

表5概括了在MDCK细胞中60小时时siRNA抑制的结果，以抑制倍数的形式表示。因此较低值表示缺少抑制而较高值表示有效抑制。siRNA在病毒基因里的位置由基因名称后的数字表示。如别处所示，数字代表siRNA在基因中的起始核苷酸。例如，NP-1496指对NP特异性的siRNA，第一个核苷酸开始于NP序列的核苷酸1496。通过将模拟转染的血凝素单位除以以所指siRNA转染所得血凝素单位而计算所示的值(倍数-抑制)；值1表示没有抑制。

在MDCK细胞系系统中检测了总共20种靶向流感病毒基因组6个片段(PB2、PBl、PA、NP、M和NS)的siRNA(表5)。约15％的测试siRNA(PBl-2257、PA-2087G和NP-1496)展示了强效，在大多数MOI＝0.001的情况抑制病毒繁殖超过100倍，在MOI＝0.01的情况抑制病毒繁殖16至64倍，不论使用的是PR8病毒还是WSN病毒。尤其是，当使用siRNANP-1496或PA-2087时，抑制是如此显著以至于培养物上清液没有可检测的血凝素活性。这些有效的siRNA靶向3种不同病毒基因片段：PB1和PA，其涉及在RNA转录酶复合体中，以及NP，其是单链RNA结合核蛋白。与其它系统中的发现一致，由这些siRNA靶向的序列都位于相对靠近编码区的3-引物端(图12)。

大约40％的siRNA显著地抑制病毒繁殖，但抑制的程度根据一些参数而变化。大约15％的siRNA有效抑制病毒繁殖而不论使用的是PR8病毒还是WSN病毒。然而，在一些siRNA的情况，抑制的程度部分取决于使用的是PR8病毒还是WSN病毒。一些siRNA仅在早期时间点(感染后24至36小时)或仅在较低感染剂量(MOI＝0.001)显著抑制病毒繁殖，如PB2-2240、PBl-129、NP-23l和M-37。这些siRNA靶向不同的病毒基因片段，相应的序列位于靠近编码区的3-引物端或5-引物端(图12)。图5A和5B代表检测结果。大约45％的siRNA对病毒滴度没有可辨别的效力，说明它们在MDCK细胞中不能有效干扰流感病毒繁殖。尤其是，这四种靶向NS基因片段的siRNA都没有显示任何抑制效力。

为了更准确地评估病毒滴度，以病毒感染的细胞获得的培养物上清液进行噬菌斑检测(60小时)，该细胞经过模拟转染或以NP-1496转染。在模拟上清液中检测到约6×10⁵pfu/ml，而在未稀释的NP-1496上清液中未检测到噬菌斑(图11C)。由于噬菌斑检测的检测限是约20pfu(噬菌斑形成单位)/ml，NP-1496对病毒繁殖的抑制是至少约30,000倍。即使在0.1的MOI，NP-1496抑制病毒繁殖约200倍。

为了确定siRNA的效价，将分级量的NP-1496转染入MDCK细胞，随后以PR8病毒感染。由血凝素检测来测量培养物上清液中的病毒滴度。随着siRNA的量减少，培养物上清液中的病毒滴度增加，如图11D所示。然而，即使只有25pmol siRNA用于转染，与模拟转染相比检测到约4倍的病毒繁殖抑制，说明NP-1496 siRNA用于抑制流感病毒繁殖的效力。

对于治疗，期望的是siRNA能够有效抑制现有的病毒感染。在典型流感病毒感染中，在感染后约4小时开始释放新的病毒粒子。为了确定siRNA是否能减少或消除现有感染情况下新释放病毒的感染，以PR8病毒感染MDCK细胞，然后以NP-1496 siRNA转染。模拟转染后病毒滴度随时间平稳地增加，而在NP-1496转染细胞中病毒滴度仅略微增加。因此病毒感染后给药siRNA是有效的。

这些结果共同表示：(i)一些siRNA可有效抑制流感病毒繁殖；(ii)流感病毒繁殖可由对不同病毒基因特异性的siRNA抑制，所述基因包括那些编码NP、PA、PB1蛋白的基因；和(iii)siRNA抑制除了发生在siRNA给药同时或给药之后受感染的细胞中以外，还发生在预先感染的细胞中。

实施例2：靶向病毒RNA聚合酶或核蛋白的siRNA抑制鸡胚胎中甲型流感病毒繁殖

材料和方法

siRNA-oligofectamine复合体形成和鸡胚胎接种。如上所述的制备siRNA。在标准条件下保持鸡卵。30μl的Oligofectamine(产品号：来自Life Technologies(现在为Invitrogen)的12252011)与30μl的Opti-MEMI(Gibco)混合，并在室温下保持5分钟。2.5nmol(10μl)siRNA与30μl的Opti-MEMI混合并加至稀释的oligofectamine。siRNA与oligofectamine在室温保持30分钟。l0天的鸡卵以siRNA-oligofectamine复合体和100μl PR8病毒(5000pfu/ml)接种。鸡卵在37℃培养所指的时间并收集尿囊液。由如上所述的HA检测测试尿囊液中的病毒滴度。

结果

为了证实MDCK细胞中的结果，还检测了siRNA在受精鸡卵中抑制病毒繁殖的能力。由于电穿孔不能用于卵，故使用了基于脂类的药剂Oligofectamine，其已经显示为促进胞内DNA寡核苷酸以及体外siRNA的摄取(25)。简言之，如图13A示意性地所示，将PR8病毒(500 pfu)或病毒加上siRNA-oligofectamine复合体注射到10天龄鸡卵的尿囊中。17小时后收集尿囊液以通过血凝素检测而测量病毒滴度。如图13B所示，当病毒(存在Oligofectamine)单独注射时，易于检测到高病毒滴度。GFP-949的共注射不能显著影响病毒滴度。(当不存在Oligofectamine时没有观察到病毒滴度的显著减少。)

对流感病毒特异性的siRNA的注射显示了与MDCK细胞中观察到的一致结果：在MDCK细胞中抑制流感病毒繁殖的相同的siRNA(NP-1496、PA2087和PBl-2257)也在鸡卵中抑制病毒繁殖，而在MDCK细胞中较无效的siRNA(NP-231、M-37和PBl-129)在受精鸡卵中也无效。因此，siRNA在受精鸡卵中也有效干扰流感病毒繁殖。

实施例3：siRNA在mRNA水平抑制流感病毒繁殖

材料和方法

如上所述地进行siRNA制备。

提取RNA、反转录和实时PCR。1×10⁷MDCK细胞以2.5nmol NP-1496电穿孔或模拟电穿孔(无siRNA)。8小时后，以MOI＝0.1接种甲型流感病毒PR8病毒。感染后1、2、和3小时，移去上清液，以Trizol试剂(Gibco)裂解细胞。根据制造商的说明纯化RNA。在37。C进行反转录(RT)1小时，使用200ng总RNA、特异性引物(见以下)，和根据制造商说明的20μl反应混合物中的Omniscript Reverse transcriptase试剂盒(Qiagen)。对mRNA、NP vRNA、NP cRNA、NS vRNA、或NS cRNA的特异性引物如下：

mRNA，dT₁₈=5’-TTTTTTTTTTTTTTTTTTTT-3’(SEQ ID NO：10754)

NNp vRNA，NP-367：5’-CTCGTCGCTTATGACAAAGAAG-3’(SEQ ID NO：10755).

NP cRNA，NP-1565R：

5’-ATATCGTCTCGTATTAGTAGAAACAAGGGTATTTTT-3’(SEQ ID NO：10756).

NS vRNA，NS-527：5’-CAGGACATACTGATGAGGATG-3’(SEQ ID NO：10757).

NS cRNA，NS-890R：

5’-ATATCGTCTCGTATTAGTAGAAACAA-3’(SEQ ID NO：10758).

1μl RT反应混合物(即，进行反转录获得的样品)和序列特异性引物用于实时PCR，使用包括SYBR Green I双链DNA结合染料的SYBR GreenPCR master mix(AB Applied Biosystems)。在ABI PRISM 7000序列检测系统(AB Applied Biosystem)中进行PCR循环，并以ABI PRISM 7000 SDS软件(AB Applied Biosystems)分析。PCR反应如下进行：50℃、2分钟，95℃、10分钟，然后95℃、15秒，和60℃、1分钟，50个循环。在0.2荧光单位读数分析循环次数。所有反应都双份进行。丢弃双份之间差异超过1.0的循环次数。然后对双份循环次数平均，从它们减去β-肌动蛋白的循环次数以对值标准化。

PCR引物如下。

对NP RNA：

NP-367：5’-CTCGTCGCTTATGACAAAGAAG-3’(SEQ ID NO：10755).

NP-46OR：5’-AGATCATCATGTGAGTCAGAC-3’(SEQ ID NO：10759).

对NS RNA：

NS-527：5’-CAGGACATACTGATGAGGATG-3’(SEQ ID NO：10757)，

NS-617R：5’-GTTTCAGAGACTCGAAACTGTG-3’(SEQ ID NO：10760).

结果

如上所述，在流感病毒复制期间，转录vRNA以产生作为更多vRNA合成模板的cRNA和作为蛋白合成模板的mRNA(1)。尽管已知RNAi以序列特异性方式(16-18)靶向于mRNA的降解，但可能vRNA和cRNA也靶向于siRNA，因为甲型流感病毒的vRNA对核酶敏感(1)。为了研究siRNA对各种RNA降解的效力，使用序列特异性引物反转录，然后实时PCR以对vRNA、cRNA和mRNA的水平定量。图1 5显示了流感病毒vRNA、mRNA和cRNA之间的关系。如图15所示，cRNA与vRNA精确互补，但mRNA在3’端含有polyA序列，开始于互补于从vRNA片段5，端下游的15-22核苷酸的位点。因此与vRNA和cRNA相比，mRNA在3，端缺少15至22核苷酸。为了区别这三种病毒RNA，在第一反转录反应中使用针对vRNA、cRNA和mRNA的特异性引物。对mRNA，使用poly dTl8作为引物。对cRNA，使用互补于mRNA中缺少的3’端RNA的引物。对vRNA，引物可沿着RNA的任何一处，只要它互补于vRNA且不太靠近5，端。以实时PCR扩增从仅一种RNA转录得到的cDNA。

流感病毒感染后，新的病毒粒子被包装并在约4小时时释放。为了确定siRNA对第一波mRNA和cRNA转录的影响，在感染后早期分离RNA。简言之，将NP-1496电穿孔入MDCK细胞。也进行模拟电穿孔(无siRNA)。6至8小时后，以MOI＝0.1接种PR8病毒。感染后1、2、和3小时，裂解细胞，分离RNA。使用对各种RNA的引物反转录而检测mRNA、vRNA和cRNA的水平，然后进行实时PCR。

图16显示了在病毒感染细胞后各时间病毒NP和NS RNA的量，这些细胞感染前6-8小时被模拟转染或以siRNANP-1496转染。如图16所示，感染1小时后，有或无NP siRNA转染的样品之间NP mRNA的量没有显著差别。转染后2小时，模拟转染组中NP mRNA增加38倍，而siRNA转染的细胞中NP mRNA的水平没有增加(或甚至轻微降低)。感染3小时后，模拟转染中mRNA水平持续增加，而接受siRNA处理的细胞中观察到NP mRNA量的持续减少。NP vRNA和cRNA表现出类似的模式，除了模拟转染中vRNA和cRNA的量增加只在感染后3小时显著。尽管不希望受任何理论束缚，这很可能是因为流感病毒的生命周期，其中mRNA转录的初次循环发生在cRNA和vRNA合成之前。

这些结果表示，与血凝素检测或噬菌斑检测测量完整活病毒的结果一致，NP siRNA处理也显著减少所有种类NP RNA的量。尽管已知siRNA主要介导mRNA的降解，此试验的数据也不排除siRNA介导NP cRNA和VRNA降解的可能性，尽管以下的结果表示由于NP mRNA减少导致NP蛋白水平减少，从而导致NP cRNA和/或vRNA稳定性降低。

实施例4：RNA干扰靶的鉴定

材料和方法

如上所述地进行未修饰siRNA的siRNA制备。修饰的siRNA也由Dharmacon合成，其中有义链或反义链或同时两条链的每个核苷酸残基的2’-羟基以2’-O-甲基取代。如对未修饰的寡核苷酸那样，修饰的寡核苷酸被脱保护并退火至互补链。凝胶电泳分析siRNA双链体的双链体形成完成度。

细胞培养，siRNA转染，和病毒感染。这些基本上如上所述。简言之，对关于修饰的NP-1496 siRNA的试验，首先以从野生型链(wt)和修饰链(m)生成的NP-1496 siRNA(2.5nmol)转染MDCK细胞，8小时后以0.1的MOI的PR8病毒感染。感染24小时后检测培养物上清液中的病毒滴度。对关于M-37 siRNA的试验，以M-37 siRNA(2.5nmo1)转染MDCK细胞，以0.01的MOI的PR8病毒感染，感染1、2、3小时后收集RNA。表2列出了M-37的有义和反义序列。

RNA提取，反转录和实时PCR基本上如上所述。用于反转录的对mRNA、M-特异性vRNA、和M-特异性cRNA的特异引物如下：

mRNA，dT₁₈＝5’-TTTTTTTTTTTTTTTTTTT-3’(SEQ ID NO：10754)

M vRNA：5’-CGCTCAGACATGAGAACAGAATGG-3’(SEQ ID NO：10761)

McRNA：5’-ATATCGTCTCGTATTTAGTAGAAACAAGGTAGTTTTT-3’(SEQ IDNO：10762).

用于M RNA的PCR引物如下：

M向前：5’-CGCTCAGACATGAGAACAGAATGG-3’(SEQ ID NO：10761)

M反向：5’-TAACTAGCCTGACTAGCAACCTC-3’(SEQ ID NO：10763)

结果

为了研究siRNA除了干扰mRNA以外还干扰vRNA和/或cRNA的可能性，合成了有义链(S或+)或反义链(AS或-)被修饰的NP-1496siRNA。该修饰(即在每个核苷酸残基以2’-O-甲基取代2，-羟基)不影响双链体形成的碱基配对，但修饰过的RNA链不再支持RNA干扰。换言之，有义链被修饰但反义链是野生型的siRNA(mS：wtAS)将支持序列与反义链互补的RNA降解，但不支持序列与有义链互补的RNA降解。相反，有义链是野生型但反义链被修饰的siRNA(wtS：mAS)将支持序列与有义链互补的RNA降解，但不支持序列与反义链互补的RNA降解。

MDCK细胞被模拟转染或以有义链被修饰而另一条链为野生型的NP-1496 siRNA(mS：wtAS)或反义链被修饰而另一条链为野生型的NP-1496 siRNA(wtS：mAS)所转染。细胞还以两条链都修饰的NP-1496siRNA(mS：mAS)转染。然后以PR8病毒感染细胞，测量上清液中的病毒滴度。如图17A所示，经受模拟转染的培养物中检测到高的病毒滴度。如所期待的，野生型siRNA(wtS：wtAS)转染的培养物中检测到很低的病毒滴度，但两条链都被修饰的siRNA(mS：mAS)转染的培养物中检测到高病毒滴度。反义链被修饰的siRNA(wtS：mAS)转染的培养物中病毒滴度高，而有义链被修饰的siRNA(mS：wtAS)转染的培养物中病毒滴度低。尽管不希望受束缚于任何理论，发明人认为siRNA双链体需要野生型反义链(-)来抑制流感病毒繁殖表示RNAi干扰的靶是mRNA(+)或cRNA(+)或两者。

为了进一步区分这些可能，检查了siRNA对相应mRNA、vRNA、和cRNA蓄积的效力。为了追踪一组同时感染的细胞的转录，感染后1、2和3小时(在释放新的病毒粒子并再次感染之前)收集siRNA转染的MDCK细胞以分离RNA。首先是用特异性引物将病毒mRNA、vRNA、和cRNA独立地转化为cDNA。然后由实时PCR对每种cDNA的水平定量。如图17B所示，当使用M-特异性siRNAM-37时，感染后1或2小时几乎检测不到M-特异性mRNA。感染3小时后，在没有M-37时易于检测到M-特异性mRNA。在以M-37转染的细胞中，M-特异性mRNA的水平减少约50％。相反，在M-37存在时，M-特异性vRNA和cRNA的水平不受抑制。尽管不希望受任何理论束缚，这些结果表示病毒mRNA可能是siRNA介导干扰的靶。

实施例5：一些siRNA对病毒RNA蓄积的作用

材料和方法

如上所述地制备siRNA。引物对mRNA、NP vRNA、NP cRNA、NSVRNA、NS cRNA、M vRNA、或M cRNA。用于反转录的对PB1 vRNA、PBl cRNA、PB2 vRNA、PB2 cRNA、PAvRNA、或PA cRNA的特异引物如下：

PBl vRNA：5’-GTGCAGAAATCAGCCCGAATGGTTC-3’(SEQ ID NO：10764)

PB1 cRNA：5’-ATATCGTCTCGTATTAGTAGAAACAAGGCATTT-3’(SEQ ID NO：10765)

PB2 vRNA：5′-GCGAAAGGAGAGAAGGCTAATGTG-3′(SEQ ID NO：10766)

PB2 cRNA：51-ATATGGTCTCGTATTAGTAGAAACAAGGTCGTTT-3’(SEQ ID NO：10767)

PA vRNA：5’-GCTTCTTATCGTTCAGGCTCTTAGG-3’(SEQ ID NO：10768)

PA cRNA：5’-ATATCGTCTCGTATTAGTAGAAACAAGGTACTT-3，(SEQ ID NO：10769)

用于PB l、PB2、和PA RNA的PCR引物如下：

PBl向前：5’-CGGATTGATGCACGGATTGATTTC-3’(SEQ ID NO：10770)

PB1:反向5’-GACGTCTGAG-CTCTTCAATGGTGGAAC-3’(SEQ ID NO：10771)

PB2向前5′-GCGAAAGGAGAGAAGGCTAATGTG-3′(SEQ ID NO：10766)

PB2反向：51-AATCGCTGTCTTGGCTGTCAGTAAG-3′(SEQ ID NO：10772)

PA向前  5’-GCTTCTTATCGTTCAGGCTCTTAGG-3’(SEQ ID NO：10768)

PA反向：5’-CCGAG-AAGCATTAAGCAAAACCCAG-3’(SEQ ID NO：10773)

结果

为了确定NP-1496是否特异性地靶向NP基因片段的降解，或不同于NP的病毒RNA的水平是否也受影响，对NS特异性的引物用于RT和实时PCR以如上所述地测量不同NS RNA种类(mRNA、vRNA、cRNA)的量。如图18所示，NS mRNA、vRNA和cRNA显示了与NP RNA相同的模式。感染3小时后，模拟转染细胞中观察到所有NS RNA种类的显著增加，而接受NP-1496 siRNA的细胞中未观察到NS RNA水平的显著变化。该结果表示不同病毒RNA的转录和复制是同等地被调节的，至少对NPRNA是如此。同等地调节意味着一种转录子的水平直接或间接地影响另一种转录子的水平。没有暗示特定机制。当NP转录子被siRNA处理降解时，其它病毒RNA的水平也减少。

为了进一步研究NP siRNA对其它病毒RNA的效力，在以NP-1496处理的细胞中测量所有病毒基因的mRNA、vRNA和cRNA的蓄积。如图1 8A所示(上板)，感染后1或2小时NP特异性mRNA低。感染3小时后，没有NP-1496的情况下易于检测到NP mRNA，而有NP-1496的情况下NP mRNA的水平保持本底水平，说明siRNA抑制特异性mRNA的蓄积。如图18A所示(中板和下板)，在NP-1496存在下，NP特异性和NS特异性vRNA和cRNA被大量抑制。这些结果证实了上述结果。此外，在NP-1496处理的细胞中，M、NS、PBl、PB2、和PA基因的mRNA、vRNA和cRNA的蓄积也被抑制(图18B、18C、和18H)。而且，对PA-2087也观察到宽的抑制效应。而且，图18E、18F、和18G左侧上板、中板和下板展示了如图18A、18B、和18C同样的结果，表示NP-1496 siRNA对病毒mRNA转录和病毒vRNA和cRNA复制的抑制。图18E、18F、和18G右侧上板、中板和下板展示了以同样浓度PA-2087进行的同样试验。如分别由图18E右边的上板、中板和下板所示，感染3小时后没有PA-2087的情况下易于检测到PA、M、和NS mRNA，而PA-2087的存在抑制PA、M、和NS mRNA的转录。如分别由图18F右边的上板、中板和下板所示，感染3小时后没有PA-2087的情况下易于检测到PA、M、和NS vRNA，而PA-2087的存在抑制PA、M、和NS vRNA的蓄积。如分别由图18G右边的上板、中板和下板所示，感染3小时后没有PA-2087的情况下易于检测到PA、M、和NS cRNA，而PA-2087的存在抑制PA、M、和NS cRNA的蓄积。此外，图1 8H显示NP特异性siRNA抑制PBl-(上板)、PB2-(中板)和PA-(下板)特异性mRNA的蓄积。

尽管不希望受任何理论束缚，发明人认为NP siRNA的宽效力可能是因为NP在结合和稳定vRNA和cRNA中的重要性，而不是因为NP特异性siRNA非特异性地靶向RNA降解。流感病毒中的NP基因片段编码单链RNA-结合核蛋白，其结合于vRNA和cRNA(图14)。在病毒生命周期中，NP mRNA首先转录和翻译。NP蛋白的主要功能是为了RNA转录、复制和包装的目的而包裹病毒基因组。没有NP蛋白时，vRNA和cRNA的全长合成被削弱。当NP siRNA诱导NP RNA降解时，NP蛋白合成被削弱，导致缺少足够的NP蛋白，随后影响其它病毒基因片段的复制。以这种方式，NP siRNA可在早期有效抑制病毒繁殖。

已经假设受感染细胞中NP蛋白的数目调节mRNA合成及基因组RNA(vRNA和cRNA)复制的水平(1)。使用NP蛋白中温度敏感的突变，此前的研究表示cRNA而非mRNA的合成在体外和体内是温度敏感的(70、71)。已经显示NP蛋白对于新生cRNA和vRNA转录子的伸长和抗终止是需要的(7l、72)。此处列出的结果证明NP-特异性siRNA抑制受感染细胞中所有病毒RNA的蓄积。尽管不希望受束缚于任何理论，很可能在NP-特异性siRNA存在下，新转录的NP mRNA被降解，导致在病毒感染后抑制NP蛋白合成。没有新合成的NP，从而抑制进一步的病毒转录和复制以及新病毒粒子的产生。

类似地，在存在PA-特异性的时，新转录的PA mRNA被降解，导致PA蛋白合成的抑制。尽管存在每流感病毒粒子的30-60拷贝的RNA转录酶(1)，没有新合成的RNA转录酶，进一步的病毒转录和复制可能受抑制。使用对PBl特异性的siRNA获得类似结果。相反，基质蛋白(M)直到病毒感染的后期才需要(1)。因此，M-特异性的siRNA抑制M-特异性mRNA而非vRNA、cRNA或其它病毒RNA的蓄积。总之，这些发现证明在流感病毒RNA转录和复制中非常需要新合成的核蛋白和聚合酶蛋白。NP-、PA-、和PBl-特异性siRNA干扰mRNA蓄积和其它病毒RNA转录的mRNA和病毒特异性机制表示，这些siRNA是流感病毒感染的尤其有效抑制物。

实施例6：一些siRNA对病毒RNA蓄积的作用不是由于干扰素应答或病毒诱导的RNA降解

使用PCR在标准条件下测量RNA水平。以下PCR引物用于测量γ-肌动蛋白RNA。

γ-肌动蛋白向前  ：5’TCTGTCAGGGTTGGAAAGTC-3’(SEQ ID NO：l0774)

γ-肌动蛋白反向：5’-AAATGCAAACCGCTTCCAAC-3’(SEQ ID NO：10775)

导致如上所述宽抑制病毒RNA蓄积的一个可能原因是受感染细胞在siRNA存在下的干扰素应答(23、65、66)。因此在Vero细胞中重复上述试验，所述细胞中缺失了包括所有α、β、和ω)基因的完整IFN基因座(67、68)(Q.G.和J.C未公开数据)。如同在MDCK细胞中，NP-、M-、和NS-特异性siRNA都由NP-1496抑制(图18D)。此外，使用PCR检测了siRNA对胞内基因包括β-肌动蛋白、γ-肌动蛋白、和GAPDH转录子水平的效力。有或无siRNA存在没有检测到转录子水平的显著差异，说明siRNA的抑制效力对病毒RNA是特异性的。这些结果说明，某些siRNA对病毒RNA的宽抑制不是细胞干扰素应答的结果。

在流感病毒感染之后，dsRNA的存在也激活靶向RNA降解的细胞途径(23)。为了检测siRNA激活该途径的效力，我们检测了该途径最重要成分磷酸化蛋白激酶R(PKR)的水平(23)。不存在病毒感染的情况下以NP-1496转染MDCK细胞不影响激活的PKR的水平(数据未显示)。流感病毒的感染导致磷酸化PKR水平增加，与此前的研究一致(65、66、69)。然而存在或不存在NP-1496的情况下该增加是相同的(数据未显示)。因此，病毒RNA蓄积的宽抑制不是siRNA存在下增加病毒诱导降解的结果。

实施例7：  RNA对小鼠流感病毒繁殖的抑制

本实施例描述了显示在流感病毒感染之前或之后给药靶向于流感病毒NP或PA转录子抑制小鼠流感病毒繁殖的试验。该抑制是剂量依赖性的，并当两种各靶向于不同流感病毒基因表达的转录子的siRNA一起给药时显示累加效应。

材料和方法

制备siRNA。这如上进行。

siRNA递送。siRNA(30或60μg GFP-949、NP-1496或PA-2087)与用于寡核苷酸阳离子聚合物转染剂的ietPEI^TM(N/P比＝5(Qbiogene，Inc.，Carlsbad，CA；Cat.No.GDSP20 130；N/P指jetPEI/siRNA混合物中每核苷酸磷酸的氮数目))或聚-L-赖氨酸(MW(vis)52,000；MW(LALLS、)41,800，Sigma Cat.No.P2636)在5％葡萄糖中室温下保持29分钟。将混合物静脉注射入小鼠眼后静脉，每小鼠200μ1，每组4只小鼠。200μl 5％葡萄糖注射进对照(无处理)小鼠。以2.5％三溴乙醇麻醉小鼠，然后注射siRNA或鼻内感染。

病毒感染。以吸管将含有病毒的缓冲液滴加入小鼠鼻子，将B6小鼠(标准试验条件下维持)鼻内感染PR8病毒，每只小鼠30ul(12,000pfu)。确定病毒滴度。感染后各时间将小鼠处死，收集肺。将肺均质化，匀浆经冷冻和解冻2次以释放病毒。感染肺中存在的PR8病毒通过感染MDCK细胞而滴定。将平底96孔板接种3×10⁴MDCK细胞/孔，24小时后去除含有血清的培养基。未稀释或从1×10^-1稀释至l×10^-7的25μl肺匀浆接种于三份孔。培养1小时后，带有4μg/ml胰蛋白酶的175μl感染培养基加至各孔。在37℃培养48小时后，由受感染细胞上清液的鸡RBC血凝素检测来确定病毒是否存在。血凝素检测在V-底96孔板中进行。上清液的系列2倍稀释液与等体积的鸡红细胞(Charies River Laboratories)0.5％悬浮液(vol/Vo1)混合，在冰上培养1小时。含有粘附、均匀层红细胞的孔记录为阳性。通过引入Reed和Muench方法感染50％孔的稀释端点(TCID₅₀)来确定病毒滴度，较低的TCID₅₀反映较低的病毒滴度。以Student t检验比较任何两组间的数据，该检验在此处试验中用于评价显著性。

图19A显示了试验结果，证实靶向病毒NP转录子的siRNA在感染之前给药时抑制小鼠流感病毒繁殖。30或60μgGFP-949或NP-1496 siRNA与jetPEI一起保持并静脉注射于小鼠，如材料和方法所述的。3小时后小鼠鼻内感染PR8病毒，每只小鼠12000pfu。感染24小时后收集肺。如图19A所示，未接受siRNA处理(NT；填充方块)或接受靶向于GFP的siRNA(GFP 60μg；空白方块)的小鼠的肺匀浆的平均log_l0TCID₅₀是4.2。以30μg靶向于NP的siRNA(NP 30gg；空白圆圈)和jetPEI预处理的小鼠中肺匀浆的平均log_l0TCID₅₀是3.9。以60μg靶向于NP的siRNA(NP 60μg；填充圆圈)和jetPEI预处理的小鼠中肺匀浆的平均log₁₀TCID₅₀是3.2。无处理组和接受60μg NP siRNA组的肺匀浆病毒滴度之间的差异是显著的(P＝0.0002)。单独小鼠的数据示于表6A(NT＝无处理)。

图19B显示了另一试验结果，证实靶向病毒NP转录子的siRNA在感染之前静脉给药时抑制小鼠流感病毒繁殖，所述给药是以含有阳离子聚合物PLL的组合物。30或60μgGFP-949或NP-1496 siRNA与PLL一起保持并静脉注射于小鼠，如材料和方法所述的。3小时后小鼠鼻内感染PR8病毒，每只小鼠12000 pfu。感染24小时后收集肺。如图19B所示，未接受siRNA处理(NT；填充方块)或接受靶向于GFP的siRNA(GFP 60μg；空白方块)的小鼠的肺匀浆的平均log₁₀TCID₅₀是4.1。以60μg靶向于NP的siRNA(NP 60μg；填充圆圈)和PLL预处理的小鼠中肺匀浆的平均log₁₀TCID₅₀是3.0。接受60μg GFP siRNA组和接受60μg NP siRNA组的肺匀浆病毒滴度之间的差异是显著的(P＝0.001)。单独小鼠的数据示于表6A(NT＝无处理)。这些数据表示靶向于流感NP转录子的siRNA在病毒感染之前给药时减少肺中病毒滴度。还表示siRNA与阳离子聚合物的混合物静脉注射有效抑制肺中流感病毒，不需要诸如流体转染等技术。

表6A.siRNA与阳离子聚合物抑制小鼠流感病毒繁殖

处理	log10TCID50
					NT (jetPEI试验    )GFP(60μg+jetPEINP(30μg+jetPEINIP(60μg+jetPENT(PLL试验  )GFP(60μg)+PLLNP(60μg)+PLL	4.34.34.03.34.04.33.3	4.34.34.03.34.34.03.0	4.04.33.73.04.04.03.0	4.04.03.73.04.0(未进行)2.7

图19C显示了另一试验结果，证实靶向病毒NP转录子的siRNA在感染之前给药抑制小鼠流感病毒繁殖，而且阳离子聚合物存在时显著增加siRNA的抑制效力。60μg GFP-949或NP-1496 siRNA与磷酸缓冲盐(PBS)或jetPEI一起保持并静脉注射于小鼠，如材料和方法所述的。3小时后小鼠鼻内感染PR8病毒，每只小鼠12000pfu。感染24小时后收集肺。如图19C所示，未接受siRNA处理(NT；空白方块)的小鼠的平均1og₁₀TCID₅₀是4.1，而接受靶向于GFP的siRNA的PBS溶液(GFP PBS；空白三角)的小鼠的肺匀浆的平均log₁₀TCID₅₀是4.4。以60μg靶向于NP的siRNA的PBS溶液(NP PBS；填充三角)的小鼠中肺匀浆的平均log₁₀TCID₅₀是4.2，显示了相对于无处理或以靶向于GFP的siRNA处理的效力轻微增加。以60μg靶向于GFP的siRNA和jetPEI(GFP PEI；空白圆圈)预处理的小鼠中肺匀浆的平均log₁₀TCID₅₀是4.2。然而，以60μg靶向于NP的siRNA和jetPEI(NP PEI；填充圆圈)处理的小鼠中肺匀浆的平均log₁₀TCID₅₀是3.2。接受GFP siRNA的PBS溶液组和接受NP siRNA的PBS溶液组的肺匀浆病毒滴度之间的差异是显著的(P＝0.04)，而接受GFP siRNA与jetPEI的组和接受NP siRNA与jetPEI的组的肺匀浆病毒滴度之间的差异是非常显著的(P＝0.003)。单独小鼠的数据示于表6B(NT＝无处理)。

表6B.siRNA与阳离子聚合物显示了抑制小鼠流感病毒繁殖的增强的效力

处理	log10TCID50
					NTGFP(60μg)+PBSNP(60μg)+PBSGFP(60μg)+jetPEINT(60μg)+jetPEI	4.34.33.74.33.3	4.34.34.34.33.0	4.04.74.04.03.7	3.74.34.03.03.0

进行其它试验以检验siRNA在感染前或感染后的各时间点给入时在感染后各时间抑制流感病毒繁殖的能力。

将siRNA如上所述地给药，除了在病毒感染前12小时给药120μgsiRNA。表6C显示了以log₁₀TCID₅₀表示的结果。比较NP-处理组与对照组的P值为0.049。

表6C

	小鼠1	小鼠2	小鼠3	小鼠4
					NT	4.3	4	4	4
GFPP-949	4.3	4	4	4
					NP-1496	4	3.7	3.7	3.3

另一试验中，将siRNA(60μg)在感染前3小时给药。鼻内给予1500pfu的PR8病毒。感染48小时后收集受感染的肺。表6D显示了以log₁₀TCID₅₀表示的结果。比较NP-处理组与对照组的P值为0.03。

表6D

	小鼠1	小鼠2	小鼠3	小鼠4
					NT	4	4	4	4
GFP-949	4.3	4	4	3.7
					NP-1496	3	3.7	3.7	3.3

另一试验中，将siRNA(120μg)在PR8病毒(1500 pfu)感染24小时后给药。感染52小时后收集受感染的肺并测量病毒滴度。表6E显示了以log₁₀TCID₅₀表示的结果。比较NP-处理组与对照组的P值为0.03。

表6E

	小鼠1	小鼠2	小鼠3	小鼠4
					GFP-949	2.3	2.7	2	2.7
NP-1496	2	2	1.7	2

其它聚合物显示为有效的siRNA递送剂。图19D是显示靶向于NP(NP-1496)的siRNA与聚(β氨基酯)(J28)一起静脉给药时抑制小鼠中流感病毒繁殖的示意图。图19E是显示靶向于NP(NP-1496)的siRNA与聚(β氨基酯)(J28或C32)一起腹膜内给药时抑制小鼠中流感病毒繁殖的示意图，而对照RNA(GFP)无显著效果。该试验基本上如上所述，除了聚合物与siRNA的比例为重量/重量比(比如，60∶1w/w)。聚合物与siRNA混合并静脉或腹膜内地给药于小鼠，3小时后鼻内感染12,000pfu的PR8病毒。24小时后收集肺并进行HA检测。J28和C32中存在的胺和双(丙烯酸酯)单体如U.S.S.N.10/446,444所述和图示。聚合物由Dr.RobertLanger惠赠。

图20显示了试验结果，证实靶向不同流感病毒转录子的siRNA表现累加效应。60μgNP-1496 siRNA、60μgPA-2087 siRNA或60μgNP-1496siRNA+60μgPA-2087 siRNA与ietPEI一起保持并静脉注射于小鼠，如材料和方法所述的。3小时后小鼠鼻内感染PR8病毒，每只小鼠12000 pfu。感染24小时后收集肺。如图20所示，未接受siRNA处理(NT；填充方块)的小鼠的肺匀浆的平均log₁₀TCID₅₀是4.2。接受60μg靶向于NP的siRNA(NP 60μg；空白圆圈)的小鼠中肺匀浆的平均log₁₀TCID₅₀是3.2。接受60μg靶向于PA的siRNA(PA 60μg；空白三角)的小鼠中肺匀浆的平均log₁₀TCID₅₀是3.4。接受60μg靶向于NP的siRNA+60μg靶向于PA的siRNA(NP+PA；填充圆圈)的小鼠中肺匀浆的平均log₁₀TCID₅₀是2.4。无处理组和接受60μgNP siRNA组、60μgPA siRNA组或60μgNPsiRNA+60μgPAsiRNA组的肺匀浆病毒滴度之间的差异是显著的，分别为P＝0.003、0.01、和0.0001。接受60μgNP siRNA或60μgNP siRNA组与接受60μgNIP siRNA+60μgPA siRNA组的肺匀浆之间的差异是显著的(P＝0.01)。单独小鼠的数据示于表7(NT＝无处理)。这些结果表示以靶向于流感NP或PA转录子的siRNA预处理减少随后以流感病毒感染的小鼠肺中病毒滴度。数据进一步说明靶向于不同病毒转录子的siRNA的组合表现累加效应，表示以靶向于不同转录子的siRNA的组合治疗可能允许达到相等效力所需每种siRNA剂量相对于单独siRNA的量减少。

表7.对小鼠流感病毒siNRA的累加效应

处理	log10TCID50
					NTNP(60μg)PA(60μg)NP+PA(各60μg)	4.33.73.72.7	4.33.33.72.7	4.03.03.02.3	4.03.03.02.0

图21显示了试验结果，证实靶向病毒NP转录子的siRNA在感染之后给药时抑制小鼠流感病毒繁殖。小鼠鼻内感染PR8病毒，500 pfu。5小时后60μgGFP-949 siRNA、60μgPA-2087 siRNA、60μg NP-1496 siRNA或60μgNP-1 496 siRNA+60μgPA-2087 siRNA与jetPEI一起保持并静脉注射于小鼠，如材料和方法所述的。给药siRNA28小时后收集肺。如图21所示，未接受siRNA处理(NT；填充方块)或接受GFP特异性的siRNAGFP-949的siRNA(GFP；空白方块)的小鼠的肺匀浆的平均log₁₀TCID₅₀是3.0。接受60μg靶向于PA的siRNA(PA 60μg；空白三角)的小鼠中肺匀浆的平均log₁₀TCID₅₀是2.2。接受60μg靶向于NP的siRNA(NP 60μg；空白圆圈)的小鼠中肺匀浆的平均log₁₀TCID₅₀是2.2。接受60μg NPsiRNA+60μgPA siRNA(PA+NP；填充圆圈)的小鼠中肺匀浆的平均log₁₀TCID₅₀是1.8。无处理组和接受60μg PA、NP siRNA、或60μgNPsiRNA+60μg PA siRNA组的肺匀浆病毒滴度之间的差异是显著的，分别为P＝0.09、0.02、和0.003。接受NP siRNA组和PA+NP siRNA组之间的肺匀浆病毒滴度差异具有0.2的P值。单独小鼠的数据示于表8(NT＝无处理)。这些数据表示靶向于流感NP和/或PA转录子的siRNA在病毒感染之后给药时减少肺中病毒滴度。

表8.受感染小鼠中siRNA抑制流感病毒繁殖

处理	log10TCID50
					NTGFP(60μg)PA(60μg)NP(60μg)NP+PA(各60μg)	3.03.02.72.72.3	3.03.02.72.32.0	3.03.02.32.31.7	3.02.71.31.71.3

实施例8：给药提供shRNA生产模板的慢病毒抑制细胞中流感病毒繁殖

如图22A所示，在U6启动子和慢病毒载体pLL3.7的终止序列之间克隆用作NP-1496a shRNA(见图22A)合成模板的寡核苷酸(Rubinson，D.，等，Nature Genetics，Vol.33，pp.401-406，2003)。该寡核苷酸插入pLL3.7多克隆位点内的HpaI和XhoI限制位点之间。该慢病毒载体还表达EGFP以方便监控转染/感染细胞。通过将包含生产NP-1496a shRNA的模板的DNA载体共转染并将载体包裹入293T细胞而生产慢病毒。48小时后，收集含有慢病毒的培养物上清液，在4℃、2000 rpm旋转7分钟，过滤通过0.45 um滤器。以1×10⁵/孔将Vero细胞接种至24孔板。过夜培养后，含有包含插入物的培养物上清液(0.25ml或1.0ml)在8ug/ml聚凝胺存在下加入各孔。在2500rpm、室温离心板1小时，然后恢复培养。感染24小时后，所得的Vero细胞系(Vero-NP-0.25和Vero-NP-1.0)与亲本(未感染的)Vero细胞通过流式细胞术分析GFP表达。注意到NP-1496a不同于NP-1496，因为在有义部分3’端意外并入一个附加核苷酸(A)和在反义部分5’端并入互补核苷酸(U)，导致20 nt长的双链体部分，而不是NP-1496中的19。(见表2)。根据本发明的其它实施例，使用NP-1496序列而不是NP-1496a序列。此外，NP-1496a shRNA的环部分不同于NP-1496 shRNA的环部分。

对照Vero细胞和以含有插入部分的慢病毒感染的Vero细胞(Vero-NP-0.25和Vero-NP-1.0)以MOI 0.04、0.2和1感染PR8病毒。感染48小时后如上所述以HA检测确定上清液中的流感病毒滴度。

在Vero细胞中检测含有用于生产NP-1496a shRNA的模板的慢病毒抑制流感病毒繁殖的能力。NP-1496a shRNA包括能形成茎-环结构的两个互补区，该结构含有与NP-1496a shRNA同样序列的双链部分。如图22B所示，含有慢病毒的上清液与Vero细胞培养过夜导致表达EGFP，表示Vero细胞被慢病毒感染。阴影曲线代表对照细胞(未感染)中平均荧光强度。当使用1ml上清液时，几乎所有细胞变成EGFP阳性，平均荧光强度高(1818)(Vero-NP-1.0)。当使用0.25 ml上清液时，大多数细胞变成EGFP阳性，平均荧光强度低(503)(Vero-NP-0.25)。

亲本Vero细胞和慢病毒感染的Vero细胞以MOI 0.04、0.2和l感染流感病毒，感染48小时后检测病毒滴度。随着MOI增加，亲本Vero细胞培养上清液中病毒滴度增加(图22C)。相反，Vero-NP-1.0细胞培养上清液中病毒滴度保持很低，表示这些细胞中流感病毒繁殖被抑制。类似地，Vero-NP-0.25细胞培养物中流感病毒繁殖也部分地被抑制。病毒滴度示于表9。这些结果表示，慢病毒表达的NP-1496 shRNA可被加工为siRNA以抑制Vero细胞中流感病毒繁殖。抑制的程度与每细胞病毒感染的程度(由EGFP水平表示)成正比。

表9.组织培养中细胞表达的siRNA抑制流感病毒繁殖

细胞系	病毒滴度
				VeroVero-NP-0.25Vero-NP-1.0	1681	64324	128648

实施例9：鼻内给药转录siRNA前体的DNA载体抑制小鼠流感产生

如上所述地构建表达NP-1496a shRNA的质粒。如图22A对NP-1496ashRNA所示的，在U6启动子和慢病毒载体pLL3.7的终止序列之间克隆用作PBl-2257 shRNA或RSV特异性shRNA合成模板的寡核苷酸。寡核苷酸的序列如下：

NP-1496a有义：

5'-

TGGATCTTAITTTCTTCGGAGATTCAAGAGATCTCCGAAAGAAATAAGATCCTITTTTC-3’(SEQ ID NO：10776)

NP-1496a反义：

5’-

TCGAGAAAAAAGGATCTTATTTCTTCGGAGATCTCTTGAATCTCCGAAGAAATAA

GATCCA-3’(SEQ ID NO：10777)

PBl-2257有义：

5’-TGATCTGTTCCACCATTGAATTCAAGAGATTCAATGGTGGAACAGATTCCTTTTTTC-3'(SEQ ID NO：10778)

PBl-2257反义：

5’-

TCGAGAAAAAAGATCTGTFCCACCATTGAATCTCTTGAATTCAATGGTGGAACAGATCA-3’(SEQ ID NO：10779)

RSV有义：

5’-TGCGATAATAATAACTGCAAGATTCAAGAGATCTTGCAGTTATATTATCGTTTTTTC-3’(SEQ ID NO：10780)

RSV反义：

5’-

TCGAGAAAAAACGATAATATAACTGCAAGATCTCTTGAATCTTGCAGTTATATTA

tCGCA-3’(SEQ ID NO：10781)

包含上述寡核苷酸的载体表达的RSV shRNA在体内加工以产生具有以下序列的有义链和反义链的siRNA：

有义：5′-CGATAATATAACTGCAAGA-3′(SEQ ID NO：10782)

反义：5′-TCTTGCAGTTATATTATCG-3′(SEQ ID NO：10783)

使用下述寡核苷酸可类似地构建PA特异性发夹：

PA-2087有义：

5’-TGCAATTGAGGAGTGCCTGATTCAAAGGATCAGGCACTCCTCAATTGCTTTTTTC-3'(SEQ ID NO：10784)

PA-2087反义：

5’-

TCGAGAAAAAAGCAATTGAGGAGTGCCTGATCTCTTGAATCAGGCACTCCTCAATTGCA-3’(SEQ ID NO：10785)

能够作为NP-1496a shRNA、PB 1-2257 shRNA、或RSV特异性shRNA表达模板的质粒DNA(各60μg)各自与40μl Infasulf^(ONY，Inc.，AmherstNY)和20μl 5％葡萄糖混合并鼻内给药于小鼠组，每组4只小鼠。无处理(NT)组中给药40μl Infasulf和20μl 5％葡萄糖。13小时后如上所述地以PR8病毒每小鼠12000 pfu鼻内感染小鼠。感染后24小时收集肺并确定病毒滴度。

测试了DNA载体表达的shRNA抑制小鼠流感病毒感染的能力。对这些试验，质粒DNA与Infasulf混合，Infasulf是萃取自牛肺的一种天然表面活性剂，类似于此前显示为促进肺中基因转移的载体(74)。使用吸管将DNA/Infasulf混合物滴注到鼻。13小时后以PR8病毒每小鼠12000 pfu鼻内感染小鼠。流感病毒感染后24小时收集肺并由MDCK/血凝素检测测量病毒滴度。

如图23所示，未给予任何质粒DNA或给予表达呼吸道合胞病毒(RSV)-特异性shRNA的小鼠中病毒滴度高。观察到给予表达NP-1496ashRNA或PBl-2257 shRNA的小鼠中病毒滴度低。当同时给予一种表达NP-1496a shRNA的流感特异性质粒DNA和另一种表达PBl-2257 shRNA的流感特异性质粒DNA时，病毒滴度更显著降低。

未接受siRNA处理(NT；空白方块)或接受编码RSV特异性shRNA的质粒(RSV；填充方块)的小鼠的肺匀浆的平均log₁₀TCID₅₀分别是4.0或4.1。接受能作为NP-1496a shRNA模板的质粒(NP；空白圆圈)的小鼠中肺匀浆的平均log₁₀TCID₅₀是3.4。接受能作为PB1-2257 shRNA模板的质粒(PB；空白三角)的小鼠中肺匀浆的平均log₁₀TCID₅₀是3.8。接受能作为NP shRNA和PB shRNA模板的质粒(NP+PB1；填充圆圈)的小鼠中肺匀浆的平均log₁₀TCID₅₀是3.2。无处理组或接受RSV特异性shRNA质粒组和接受NP shRNA质粒、PB1 shRNA质粒、或NP和PB1 shRNA质粒组的肺匀浆病毒滴度之间的差异分别具有0.049、0.124、和0.004的P值。单独小鼠的数据示于表10(NT＝无处理)。这些数据表示DNA载体表达的shRNA可被加工为siRNA以抑制小鼠流感病毒繁殖，并证明Infasulf是用于递送可表达shRNA的质粒的合适载体。尤其是，这些数据表示靶向于流感NP和/或PBl转录子的shRNA当在病毒感染后给药时减少肺中病毒滴度。

表10.小鼠中表达的shRNA抑制流感病毒繁殖

处理	log10TCID50
					NTRSV(60μg)NP(60μg)PB1(60μg)NP+PBB1(60μg各)	4.34.34.04.03.7	4.04.03.74.03.3	4.04.03.03.73.0	4.34.03.03.33.0

实施例10A：向血管系统或呼吸道递送siRNA抑制肺中萤光素酶活性

siRNA获自Dharmacon，如上所述地脱保护和退火。NP(NP-1496)、PA(PA-2087)、PB1(PB1-2257)、和GFP的siRNA序列如上所述。Luc-特异性siRNA描述于(McCaffrey，AP，等.，Nature，418：38-39)。

pCMV-luc DNA(Promega)与PEI(Qbiogene，Carlsbad，CA)以10的氮/磷摩尔比(N/P比)室温下混合20分钟。对于静脉注射，含有60μgDNA的200μl混合物眶后注射到8周大的雄性C57BL/6小鼠(Taconic Farms)。对于气管内给药，使用Penn Century Model IA-IC吹入器将含有30μg或60μg DNA的50μl混合物给药于麻醉小鼠的肺。

将Luc-特异性或GFP特异性siRNA与ietPEI以5的N/P比在室温下混合20分钟而形成siRNA-PEI组合物。对静脉注射，含有指定量siRNA的200μl混合物眶后注射。对肺给药，气管内递送50μl。

pCMV-luc DNA给药各个时间后，收集肺、脾、肝、心脏和肾并在Cell Lysis Buffer(细胞裂解缓冲液)(Marker Gene Technologies，Eugene，OR)中匀浆。以Luciferase Assay System(荧光素酶测定系统)(Promega)分析发光，Optocomp I发光计(MGM Instruments，Hamden，CT)测量。匀浆中的蛋白浓度以BCA检测(Pierce)测量。

为了确定PEI介导的核酸递送在小鼠中的组织分布，静脉注射pCMV-luc DNA-PEI复合物，24小时后测量各器官中Luc活性。肺中活性最高，至少4天检测到Luc活性，而在心、肝、脾和肾中，水平低100-1,000倍且在注射后短时间检测到。当DNA-PEI复合物鞘内滴注时，肺中也检测到显著的Luc活性，尽管比静脉注射后水平低。

为了检测PEI在静脉注射后促进肺对siRNA摄取的能力，对小鼠首先鞘内注射给予pCMV-luc DNA-PEI复合物，然后静脉注射与PEI络合的Luc特异性siRNA、与PEI络合的对照GFP特异性siRNA、或同样体积的5％葡萄糖。24小时后，接受Luc siRNA的小鼠肺中Luc活性比接受GFP siRNA或无处理的小鼠肺中Luc活性低17倍。因为Luc siRNA仅能在转染DNA载体的同一肺细胞中抑制Luc表达，这些结果表示siRNA-PEI混合物的静脉注射达到对肺中靶转录子的有效抑制。

为了检测PEI在肺给药后促进肺对siRNA摄取的能力，对小鼠首先静脉注射给予pCMVDNA-PEI复合物，然后鞘内注射与PEI混合的Luc特异性siRNA、与PEI混合的对照GFP特异性siRNA、或同样体积的5％葡萄糖。24小时后，检测肺匀浆中萤光素酶活性。萤光素酶siRNA处理的小鼠中萤光素酶活性比以GFP siRNA处理的小鼠低6.8倍。这些结果表示siRNA-PEI混合物的肺给药达到对肺细胞中靶转录子的有效抑制。

实施例10B：向呼吸系统递送siRNA抑制肺中亲环蛋白B

亲环蛋白B是一种在哺乳动物中广泛表达的内源基因。为了检测直接递送至呼吸系统的siRNA抑制内源基因表达的能力，远亲后代Blackwiss小鼠(体重约30 g或更多)由异氟醚/氧气麻醉，靶向于亲环蛋白B的siRNA(Dharmacon，D-001136-01-20 siCONTROL Cyclophilin B siRNA、)(人/小鼠/大鼠)或对照GFP-949 siRNA(2mg/kg)鼻内给药于小鼠的组，每种siRNA给药2只小鼠。给药24小时后收集肺。从肺提取RNA，使用随机引物进行反转录。然后使用亲环蛋白B和GAPDH Taqman基因表达检测(AppliedBiosystems)进行实时PCR。结果(表11-1)显示靶向于亲环蛋白B的siRNA沉默了70％亲环蛋白B。

表11：肺中亲环蛋白B的抑制

平均    标准化     平均标准化    沉默％

PBS-1    5.395406  4.288984

PBS-2    3.182562

GFP-1    2.547352  3.752446      12.50968

GFP-2    4.957539

Cyclo-1  1.173444  1.256672      70.7

Cyclo-2  1.339901--

表11-2：NP基因中的靶部分

ID编号	序列		核苷酸位置
				1	agcaaaagcaggguagaua	(SEQ ID NO：10786)	1-19
2	gcaaaagcaggguagauaa	(SEQ ID NO：10787)	2-20
				3	caaaagcaggguagauaau	(SEQ ID NO：10788)	3-21
4	aaaagcaggguagauaauc	(SEQ ID NO：10789)	4-22
				5	aaagcaggguagauaauca	(SEQ ID NO：10790)	5-23
6	aagcaggguagauaaucac	(SEQ ID NO：10791)	6-24

实施例11：向呼吸系统直接递送裸siRNA抑制流感病毒

材料和方法

如上所述地进行siRNA制备、病毒感染、肺收集、和流感病毒滴度检测。使用异氟醚(吸入给药)麻醉小鼠。以鼻内滴管递送50μl体积的siRNA。使用Student’s T检验法计算p值。

结果

磷酸缓冲盐(PBS)中的siRNA(NP-1496)给药于小鼠组(每组5只小鼠)。给药siRNA3小时后以流感病毒(2000 PFU)感染小鼠。感染24小时后收集肺和测量病毒滴度。在预备试验中以三溴乙醇麻醉小鼠，以鼻内滴管给药2 mg/kg的siRNA。观察到相对于对照病毒滴度的减少，尽管未达到统计显著度(数据未显示)。

在第二个试验中，使用异氟醚/O₂麻醉Black Swiss小鼠。PBS中的siRNA以各种量给药于小鼠，每只小鼠50 ul。3个不同组(每组5只小鼠)以鼻内滴管接受2mg/kg、4mg/kg、或10mg/kg PBS中的siRNA的剂量。第四组仅接受PBS作为对照。3小时后，使用异氟醚/O₂再次麻醉小鼠，鼻内给予30ul的PR8病毒(2000pfu＝4×致死剂量)。感染24小时后收集小鼠肺，匀浆并如上所述使用TCID₅₀评价来测量病毒滴度。对肺匀浆的5倍稀释而不是10倍稀释进行。

三组处理组各自和对照组的小鼠之间观察到显著和剂量依赖性的病毒滴度差异(表12)。接受2mg/kg、4mg/kg、和10mg/kg剂量的组相对于对照病毒滴度的减少分别为3.45倍(p＝0.0125)、4.16倍(p＝0.0063)、和4.62倍(p＝0.0057)。

总之，这些结果证明水性介质中递送到呼吸系统的siRNA在没有增强递送的特异性药剂时的效力。

表12：裸siRNA的鼻内递送抑制流感病毒繁殖

处理	logl0TCID50					平均	P值
								PBS	26718.37	45687.78	45687.78	15625	2671 8.37	32087.46
NP(2mg/kg)	15625	15625	3125	3125	9137.56	9327.51	0.008
								NP(4mg/kg)	9137.56	9137.56	5343.68	9137.56	5343.68	7620	0.004
NP(10mg/kg)	9137.56	9137.56	9137.56	3125	3125	6732.53	0.003

实施例12：向呼吸系统直接递送裸siRNA抑制小鼠流感病毒繁殖

本实施例证实了上述结果，并证明水性介质中递送到呼吸系统的靶向于NP的siRNA在没有增强递送的药剂时抑制肺中流感病毒繁殖。6μg、15μg、30μg、和60μg于PBS中的NP-1496 siRNA或60μg GFP-949 siRNA鼻内滴注到小鼠，大致如上所述，除了小鼠在siRNA递送2小时后鼻内感染PR8病毒，每只小鼠1000pfu。感染24小时后收集肺。水性介质中鼻内滴注的NP特异性siRNA在没有递送剂时有效抑制流感病毒。三组处理组各自和对照组的小鼠之间观察到显著和剂量依赖性的病毒滴度差异(表13)。

表13：裸siRNA抑制肺中流感病毒繁殖

处理	TCID50					平均	P值
								PBS	125	365.5	213.7	365.5	125	239.95
GFP(60μg)	125	213.7	213.7	213.7	365.5	226.32
								NP(6μg)	213.7	213.7	125	213.7	42.7	161.8	0.263
NNP(15μg)	125	125	42.7	25	73.1	78.17	0.024
								NP(30μg)	8.5	125	42.7	125	14.6	63.18	0.019
NP(60μg)	73.1	14.6	25	25	25	32.54	0.006

实施例13：修饰的siRNA介导有效沉默

为了研究含有修饰核苷酸的siRNA的沉默效力，合成含有在每条链的代替核糖核苷酸具有2’-O-甲基修饰的有义链和反义链的NP-1496 siRNA，并与未修饰的NP-1496 siRNA比较测试。2’-O-甲基修饰的NP-1496 siRNA序列如下(2’-O-甲基示为修饰核苷酸前面的“m”)：

有义：5’-GmGA mUCmU UmAU mUUmC UmUC mGGmA G dTdT-3’(SEQ ID NO：10792)

反义    ：5’-mCUmC CmGA mAGmA AmAU mAAmG AmUC mC dTdT-3’(SEQ IDNO：10793)

根据制造商的指导，使用lipofectamine 2000(Invitrogen)将2’-O-甲基修饰的NP-1496 siRNA和未修饰的NP-1496 siRNA转染到24孔板中的Vero细胞。转染6小时后，抽吸培养基。将细胞以MOI 0.1接种200μl的PR8病毒。感染24、36和48小时后收集培养上清液。如上所述地确定病毒滴度。2’-O-甲基修饰的NP 1496比未修饰的NP 1496显示略微抑制病毒繁殖。结果见表14。

表14：使用修饰的siRNA有效抑制流感病毒繁殖

HA·单位	24h	36h	48h
				No siRNA对照	4	8	16
未修饰  NP1496(400uM)	1	2	8
				修饰    NP1496(100uM)	1	2	8
修饰    NP1496(200uM)	1	2	4
				修饰    NP1496(400uM)	1	1	4

实施例14：向呼吸系统直接口气管(oraltracheal)递送裸siRNA抑制流感病毒

如上所述地进行siRNA制备、病毒感染、肺收集、和流感病毒滴度检测。使用三溴乙醇(腹膜内注射给药)麻醉小鼠。以口气管注射递送175μl体积的1mg/kg siRNA。

1mg/kg siRNA(NP-1496)和5％葡萄糖中的30ul Infasurf给药于小鼠组(每组5只小鼠)。给药siRNA3小时后以流感病毒(2000 PFU)感染小鼠。感染24小时后收集肺和测量病毒滴度。

在第二个试验中，腹膜内给药三溴乙醇麻醉Black Swiss小鼠。PBS中的NP-1496 siRNA和GFP-949 siRNA气管内给药于小鼠，每只小鼠50ul。第三组仅接受PBS作为对照。3小时后，使用异氟醚/O₂再次麻醉小鼠，鼻内给予30ul的PR8病毒(2000pfu＝4×致死剂量)。感染24小时后收集小鼠肺，匀浆并如上所述使用TCID₅₀评价来测量病毒滴度。对肺匀浆的5倍稀释而不是10倍稀释进行。

总之，这些结果证明水性介质中递送到呼吸系统的siRNA在没有增强递送的特异性药剂时的效力。

实施例15：核苷酸突变耐受研究以选择靶向广谱流感病毒的siRNA

该实施例证明其反义链与抑制区内靶转录子小于100％互补(如在互补于靶转录子的19碱基对区内)的siRNA介导有效沉默。结果证明此处所述的RNAi将有效抑制宽范围的序列不同于PR8靶部分的流感毒株。

双荧光素酶检测用于评价siRNA抑制流感基因表达的能力，该流感基因不是100％互补于siRNAl9核苷酸抑制区内的反义链。人与禽流感病毒毒株(使用PR8作为标准)比对获得的错配使用位点引导的诱变试剂盒(Stratagene)引入DNA载体(psiCHECK)，即流感靶位点被修饰以包括相对于PR8病毒的1或2个差异，特异性差异对应于人类或禽流感毒株中的一个或多个中发现的差异。

表15显示了试验结果，证明病毒NP靶(对NP-1496的靶)中的变异没有实质降低RNAi活性。(数据是三次试验平均数)。测试了靠近反义链5’或3’端位置或靠近中间的错配。

表15：反义链和靶区之间错配对NP-1496沉默的影响

	原始	A3至G3	T9至C9	C12至T12	C15至T15	A18至G18
							花虫荧光素酶沉默(％)	85.6	81.8	58.3	67.8	72.9	54.7
与原始相比剩余的沉默(％)	100	91.3	65.1	75.7	81.4	61.1

病毒PA靶(PA-2087或PA-8282的靶)的变异不会实质降低RNAi活性。然而，157种人类流感毒株中7种毒株中的G18至A18突变确实实质影响了RNA干扰活性。测试了靠近反义链5’或3’端位置或靠近中间的错配。反义链抑制区与靶之间两个错配的存在减少沉默约70-75％，但仍观察到有用程度的沉默(表16)。

表16：反义链和靶区之间错配对PA-2087或PA-8242沉默的影响

	原始	A4至G4	T6至A6	T6至C6	C15至T15	G18至A18	A19至G19	T6至C6和C15至T15
									花虫荧光素酶沉默(％)	91.7	80.8	75.9	88.8	87.5	7.0	89.3	26.8
与原始相目比剩余的沉默(％)	100	88.1	82.8	96.9	95.5	7.6	97.4	29.3

表1 7显示了试验结果，证明病毒PB2靶(对PB2-38 17的靶)中的变异没有实质降低RNAi活性。(数据是三次试验平均数)。

表17：反义链和靶区之间错配对PB2-3817沉默的影响

	原始	A17至G17	A18至T18
				花虫荧光素酶沉默(％)	86.7	73.4	75.8
与原始相比剩余的沉默(％)	100	100	87.4

表18显示了试验结果，证明病毒PBl靶(对PBl-6124的靶)中的变异没有实质降低RNAi活性。(数据是三次试验平均数)。测试了靠近反义链5’或3’端位置或靠近中间的错配。反义链抑制区与靶之间两个错配的存在减少沉默约70-75％，但仍观察到有用程度的沉默。

表18-1：反义链和靶区之间错配对PBl-6124沉默的影响

	原始	C15至T15	A1至G1	T2至C2	G3至A3	A1至T1和G3至A3
							PBl(Lab ID#6124 siRNA)花虫荧光素酶沉默(％)	84.1	71.8	82.8	84.5	74.9	73.9
与原始相比剩余的沉默(％)	100	85.4	98.5	100	89.1	87.9

表18-2：反义链和靶区之间错配对PBl-6129沉默的影响

	原始	T3至C3	T7至C7	T2至C2	C10至T10	T3至C3和C10至TI0
							PBl(Lab ID#6129 siRNA)花虫荧光素酶沉默(％)	86.4	87.3	84.4	84.5	813	59.6
与原始相比剩余的沉默(％)	100	100	97.8	100	94.2	68.3

除了以上表格所述的结果，本实施例还证明本发明的十种示例siRNA双链体耐受siRNA反义链核苷酸序列和病毒转录子靶区核苷酸序列之间的错配。本实施例中，确定了21种预先鉴定的siRNA耐受靶序列突变的能力。为了达到此，使用PR8毒株作为参考比对了所有人和禽流感基因序列(提供于www.lanl.flu.gov)的靶位点。鉴别了单核苷酸多态性(SNP)并使用位点引导诱变引入双-荧光素酶报告构建体。含有对照靶序列(PR8)或变体的表达载体随后转染Vero细胞，并伴有50 nM合适靶向的siRNA以确定每种siRNA耐受核苷酸错配的敏感度。

21种siRNA中，10种siRNA表现高程度的沉默(％沉默)并高度耐受靶位点多态性。表19概述了10种siRNA(INFsi-1至INFsi-8和G1499和G4276)的沉默百分比数据。显示了每种siRNA的核苷酸序列，作为位点引导诱变的靶的核苷酸加粗并加下划线。“错配”栏表示原始核苷酸和其在siRNA中沿着核苷酸位置原始核苷酸被取代的位置(突变核苷酸)(显示在括号中)。沉默百分比是相对于天然(PR8)观察到沉默的百分比。因此，100％相对沉默表示相比于siRNA沉默精确匹配靶序列(PR8)，对siRNA的功能没有影响。相对沉默百分比的减少代表siRNA对靶序列中错配的敏感度(即，较低百分比等于siRNA功能减少；“功能”在此定义为siRNA降解其靶RNA的能力)。

表19：siRNA对天然发生的靶位点点突变的敏感度

siRNA	siRNA核苷酸序列	错配		相对％沉默
					原始核苷酸(位置)	突变核苷酸(位置)
		G3789(INFsi-1)	CGGGACTCTAGCATACTTA(SEQ ID NO：11482)				G(3)	A(3)	100％
G(4)	A(4)			100％
					C(8)	T(8)	72.4％
T(9)	C(9)			50.1％
					A(15)	G(15)	81.9％
C(16)	G(16)			0
					T(18)	G(18)	74.2％
G3807INFsi-2)	ACTGACAGCCAGACAGCGA(SEQ ID NO：11483)			C(2)				A(2)	100％
		C(6)	T(6)		91.8％
				C(9)		T(9)	50.7％
		A(15)+G(16)	G(15)+A(16)		41.5％
				G3817(INFsi-3)		AGACAGGCGACCAAAAGAAT(SEQ ID NO：11484)	A(17)	G(17)	100％
A(18)	T(18)	87％
			A(18)		C(18)		80.5％
T(19)	C(19)	95.7％
			T(19)		A(19)		100％
G6124(INFsi-4)	ATGAAGATCTGTTCCACCA(SEQ ID NO：11485)	A(1)						T(1)	100％
			A(1)	G(1)	98.5％
		I(2)				C(2)	100％
			G(3)	A(3)	89.1％
		A(5)				G(5)	94.7％
			T(8)	C(8)	77％
		T(12)				C(12)	100％
			C(15)	T(15)	85.4％
		A(1)+G(3)				T(1)+A(3)	87.9％
			T(8)+C(15)	C(8)+T(15)	32.2％
		G6129(INFsi-5)				GATCTGTTCCACCATTGAA(SEQ ID NO：11486)	T(3)	C(3)	100％
T(7)	C(7)		97.8％
				C(10)	T(10)		94.2％
T(3)+C(10)	C(3)+T(10)		68.3％
				G8282(INFsi-6)	GCAATTGAGGAGTGCCTGA(SEQ ID NO：11487)		A(4)	G(4)	88.1％
T(6)	A(6)	82.8％
			T(6)			C(6)	96.9％
C(15)	T(15)	95.5％
			G(18)			A(18)	7.6％
A(19)	G(19)	97.4％
			T(6)+C(15)			C(6)+T(15)	29.3％
G8286(INFsi-7)	TTGAGGAGTGCCTGATTAA(SEQ ID NO：11488)	T(2)						C(2)	100％
			T(2)	A(2)	100％
		G(8)				A(8)	100％
			C(11)	T(11)	100％

		G(14)	A(14)	85.2％
					A(15)	G(15)	95.4％
		G1498(INFsi-8)	GGATCTTATTTCTTCGGAG(SEQ ID NO：11489)	A(3)				G(3)	95.7％
T(9)	C(9)				86.5％
				C(12)		T(12)	85.4％
C(15)	T(15)				91.7％
				A(18)		G(18)	94.4％
G1499	GATCTTATTTCTTCGGAGA(SEQ ID NO：11490)				A(2)			G(2)	63.6％
		T(8)	C(8)	27.5％
					C(11)	T(11)	38.3％
		C(14)	T(14)	36.8％
					A(17)	G(17)	33.2％
		G4276	ACCTATGACTGGACTCTAA(SEQ ID NO：11491)	C(3)				A(3)	100％
C(3)	T(3)				99.5％
				A(5)		T(5)	95.1％
T(6)	C(6)				99％
				C(9)		T9(9)	89.5％
T(15)	C(15)				38.1％
				T(15)		G(15)	57.4％
T(15)	A(15)				40.8％
				C(16)		T(16)	47.5％
A(18)	G(18)				82.2％
				C(9)+T(15)		T(9)+A(15)	17.4％
C(16)+A(18)	T(16)+G(18)				28.4％
				T(15)+C(16)+A(18)		G(15)+T(16)+G(18)	4.9％
T(15)+C(16)+A(1g)	A(15)+T(16)+G(18)				10.3％
				e(3)+A(5)+T(6)+C(9)+A(18)		T(3)+T(5)+C(6)+T(9)+G(18)	7.6％

如表19所示，70种含有SNP的禽/人靶中只有19种破坏siRNA功能的超过30％。这些突变体中的两种中，INFsi-2已经在位置9改变(对siRNAINFsi-2的突变-9和对siRNA INFsi-1的突变-4)，其靠近RISC介导的裂解位点并预测为对碱基对错配尤其敏感。令人惊讶的是，含有两个靶位点多态性的四种变体中的三种显示了靶裂解水平的显著降低(如siRNAINFsi-4)。携带单个多态性的变体都没有显著阻止siRNA功能。

这些数据表示，10种siRNA表现对大多数人和禽流感病毒毒株的宽的靶向性，证明10种siRNA具有作为有效RNAi治疗剂的多基因靶向策略的巨大潜力。

表20中，表2中最高度保守的序列已经与取自甲型流感病毒序列变体的其它19-mer序列匹配，该19-mer序列具有仅1或几个核苷酸错配而不同于最初19-mer序列。通过以表2所示高度保守19-mer序列片段作为参考序列，搜索表1所列序列而得到表20中的19-mer序列。对每个19-mer参考序列，在每个靶甲型流感病毒序列中发现最匹配19-mer片段的靶片段。最接近匹配的靶片段是在参考片段和靶片段之间具有最少数目核苷酸差异的片段。如果两个靶片段与参考片段具有相同数目的核苷酸差异，那么优选能在靶片段有义链与参考片段反义链之间能形成更多GU摇摆碱基对的靶片段。

表20-1.从表1-1所列甲型流感片段1(PB2)序列得到的保守和小变体19-mer序列。保守序列匹配所列病毒序列的至少89％，变体含有从参考序列的3个或更少核苷酸变化。

  Seq     Ref

                匹配序列              ％总数    5519    11    CAGCGACCAAAAGgADDCG    0.3％

  ID      ID

  1       1    GCCAGACAGCGACCAAAAG    99.5％    5520          CAGCGACCAAAgGAAUUCG    0.1％

  5484    1    GCCAGACAGCGACCAAAgG    0.1％     5521          CAGCGACCAAAAGAuUUCG    0.1％

  5485    1    GuGAGACAGCGACCAAAAG    0.2       5522    11    CgaCGAuCAAAAGAAUUCG    0.1％

  5486    1    GCCAGACgaCGAuCAAAAG    0.1％     12      12    ACUUACUGACAGCCAGACA    99.1％

  2       2    AGCCAGACAGCGACCAAAA    99.5％    5523    12    ACUUACUGACAGuCAGACA    0.2％

  5487    2    AGCCAGACAGCGACCAAAg    0.1％     5524    12    ACUUACUGAuAGCCAGACA    0.3％

  5488    2    AGuCAGACAGCGACCAAAA    0.2％     5525    12    gCUUACUGACAGCCAGACg    0.1％

  5489    2    AGCCAGACgaCGAuCAAAA    0.1％     5526    12    gCUUACcGACAGCCAGACA    0.2％

  3       3    ACAGCCAGACAGCGACCAA    99.3％    13      13    CAUACUUACUGACAGCCAG    99.1％

  5490    3    ACAGuCAGACAGCGACCAA    0.2％     5527    13    CAUACUUACUGACAGuCAG    0.2％

  5491    3    AuAGCCAGACAGCGACCAA    0.3％     5528    13    CAUACUUACUGAuAGCCAG    0.3％

  5492    3    ACAGCCAGACgaCGAuCAA    0.1％     5529    13    CAUgCUUACUGACAGCCAG    0.1％

  4       4    GACAGCCAGACAGCGACCA    99.3％    5530    13    CAUACUUACcGACAGCCAG    0.2％

  5493    4    CACAGuCAGACAGCGACCA    0.2％     14      14    CUUACUGACAGCCAGACAG    99.1％

  5494    4    GAuAGCCAGACAGCGACCA    0.3％     5531    14    CUUACUGACAGuCAGACAG    0.2％

  5495    4    GACAGCCAGACgaCGAuCA    0.1％     5532    14    CUUACUGAuAGCCAGACAG    0.3％

  5       5    CAGACAGCGACCAAAAGAA    99.3％    5533    14    CUUACcGACAGCCAGACAG    0.2％

  5496    5    CAGACAGCGACCAAAAGgA    0.3％     5534    14    CUUACUGACAGCGAGACga    0.1％

  5497    5    CAGACAGCGACCAAAgGAA    0.1％     15      15    GACAGCGACCAAAAGAAUU    99.1％

  5498    5    CAGACAGCGACCAAAAGAu    0.1％     5535    15    GACAGCGACCAAAAGgAUU    0.3％

  5499    5    CAGACgaCGAuCAAAAGAA    0.1％     5536    15    GACAGCGACCAAAgGAAUU    0.1％

  6       6    CAGCCAGACAGCGACCAAA    99.3％    5537    15    GACAGCGACCAAAAGAuUU    0.1％

  5500    6    CAGuCAGACAGCGACCAAA    0.2％     5538    15    GACgaCGAuCAAAAGAAUU    0.1％

  5501    6    uAGCCAGACAGCGACCAAA    0.3％     16      16    AUACUUACUGACAGCCAGA    99.1％

  5502    6    CAGCCAGACgaCGAuCAAA    0.1％     5539    16    AUACUUACUGACAGuCAGA    0.2％

  7       7    AGACAGCGACCAAAAGAAU    99.1％    5540    16    AUACUUACUGAuAGGCAGA    0.3％

  5503    7    AGACAGCGACCAAAAGgAU    0.3％     5541    16    AUgCUUACUGACAGCCAGA    0.1％

  5504    7    AGACAGCGACCAAAgGAAU    0.1％     5542    16    AUACUUACCGACAGCCAGA    0.2％

  5505    7    AGACACCGACCAAAAGAUU    0.1％     17      17    ACUGACAGCCAGACAGCGA    99.0％

  5506    7    AGACgaCGAuCAAAAGAAU    0.1％     5543    17    ACUGACAGuCAGACAGCGA    0.2％

  8       8    CCAGACAGCGACCAAAAGA    99.1％    5544    17    ACUGAuAGCCAGACAGCGA    0.3％

  5507    8    CCAGACAGCGACCAAAAGg    0.3％     5545    17    ACcGACAGCCAGACAGCGA    0.2％

  5508    8    CCAGACAGCGACCAAAgGA    0.1％     5546    17    ACUGACAGCCAGACgaCGA    0.1％

  5509    8    uCAGACAGCGACCAAAAGA    0.2％     18      18    GCAUACUUACUGACAGCCA    99.0％

  5510    8    CCAGACgaCGAuCAAAAGA    0.1％     5547    18    GGAUACUUACUGACAGuCA    0.2％

  9       9    ACAGCGACCAAAAGAAUUC    99.1％    5548    18    GCAUACUUACUGAuAGCCA    0.3％

  5511    9    ACAGCGACCAAAAGgAUUC    0.3％     5549    18    GCAUgCUUACUGACAGCCA    0.1％

  5512    9    ACAGCGACCAAAgGAAUUC    0.1％     5550    18    aCAUACUUACUGACAGCCA    0.1％

  5513    9    ACAGCGACCAAAAGAuUUU    0.1％     5551    18    GCAUACUUACCGACAGCCA    0.2％

  5514    9    ACgaCGAUCAAAAGAAUUC    0.1％     19      19    AGCAUACUUACUGACAGCC    99.0％

  10      10   UACUUACUGACAGCCAGAC    99.1％    5552    19    AGCAUACUUACUGACAGuC    0.2％

  5515    10   UACUUACUGACAGuCAGAC    0.2％     5553    19    AGCAUACUUACUGAUAGCC    0.3％

  5516    10   UACUUACUGAuAGCCAGAC    0.3％     5554    19    AGCAUGCUUACDGACAGCC    0.1％

  5517    10   UgCUUACUGACAGCCAGAC    0.1％     5555    19    AaCAUACUUACDGACAGCC    0.1％

  518     10   UACUUACcGACAGCCAGAC    0.2％     5556    19    AGCAUACUUACCGACAGCC    0.2％

  11      11   CAGCGACCAAAAGAAUUCG    99.1％    20      20    UGACAGCCAGACAGCGACC    99.0％

                                                5557    20    UGACAGuCAGACAGCGACC    0.2％

5558    20    UGAuAGCCAGACAGCGACC    0.3％    5604    28    UCUAaCAUACUUACUGACA    0.1％

5559    20    cGACAGCCAGACAGCGACC    0.2％    5605    28    UCUAGCAUACUUACcGACA    0.2％

5560    20    UGACAGCGAGACgaCGAuC    0.1％    29      29    CAAAAGAAUUCGGAUGGCC    98.6％

21      21    UACUGACAGCCAGACAGCG    99.0％   5606    29    CAAAAGgAUUCGGAUGGCC    0.2％

5561    21    UACUGACAGuCAGACAGCG    0.2％    5607    29    CAAAgGAAUUCGGAUGGCC    0.1％

5562    21    UACUGAuAGCCAGACAGCG    0.3％    5608    29    CAAAAGAAUUCGaAUGGCC    0.6％

5563    21    UACcGACAGCCAGACAGCG    0.2％    5609    29    CAAAAGAuUUCGGAUGGCC    0.1％

5564    21    UACUGACAGCCAGACgaCG    0.1％    5610    29    CAAAAGgAUUCGaAUGGCC    0.1％

22      22    UUACUGACAGCCAGACAGC    99.0％   30      30    AAAAGAAUUCGGAUGGCCA    98.6％

5565    22    UUACUGACAGuCAGACAGC    0.2％    5611    30    AAAAGgAUUCGGADGGCCA    0.2％

5566    22    UUACUGAuAGCCAGACAGC    0.3％    5612    30    AAAGGAAUUCGGAUGGCCA    0.1％

5567    22    UUACcGACAGCCAGACAGC    02％     5613    30    AAAAGAAUUCGaAUGGCCA    0.6％

5568    22    UUACUGACAGCCAGACgaC    0.1％    5614    30    AAAAGAuUUCGGAUGGCCA    0.1％

23      23    CUGACAGCCAGACAGCGAC    99.0％   5615    30    AAAAGgAUUCGaAUGGCCA    0.1％

5569    23    CUGACAGuCAGACAGCGAC    0.2％    31      31    GACCAAAAGAAUUCGGAUG    98.5％

5570    23    CUGAuAGCCAGACAGCGAC    0.3％    5616    31    GACCAAAAGgAUUCGGAUG    0.2％

5571    23    CcGACAGCCAGACAGCGAC    0.2％    5617    31    GACCAAAgGAAUUCGGAUG    0.1％

5572    23    CUGACAGCCAGACgaCGAu    0.1％    5618    31    GAuCAAAAGAAUUCGGAUG    0.1％

24      24    ACUCUAGCAUACUUACUGA    98.9％   5619    31    GACCAAAAGAAUUCGaAUG    0.6％

5573    24    ACUCUAGCAUgCUUACUGA    0.1％    5620    31    GACCAAAAGAuUUCGGAUG    0.1％

5574    24    ACUuUAGCAUACUUACUGA    0.2％    5621    31    GACCAAAAGgAUUCGaAUG    0.1％

5575    24    ACUaUAGCAUACUUACUGA    0.1％    32      32    CGACCAAAAGAAUUCGGAU    98.5％

5576    24    ACUCCAGCAUACUUACUGA    0.3％    5622    32    CGACCAAAAGgAUUCGGAU    0.2％

5577    24    ACUCUAaCAUACUUACUGA    0.1％    5623    32    CGACCAAAgGAAUUCGGAU    0.1％

5578    24    ACUCUAGCAUACUUACcGA    0.2％    5624    32    CGAUCAAAAGAAUUCGGAU    0.1％

25      25    UAGCAUACUUACUGACAGC    98.7％   5625    32    CGACCAAAAGAAUUCGaAU    0.6％

5579    25    UAGCAUACUUACUGACAGu    0.2％    5626    32    CGACCAAAAGAuUUCGGAU    0.1％

5580    25    UAGCAUACUUACUGAUAGC    0.3％    5627    32    CGACCAAAAGgAUUCGaAU    0.1％

5581    25    UAGCAUgCUUACUGACAGC    0.1％    33      33    AAAGAAUUCGGAUGGCCAU    9835％

5582    25    CAGCAUACUUACUGACAGC    0.3％    5628    33    AAAGgAUUCGGAUGGCCAU    0.2％

5583    25    UAaCAUACUUACUGACAGC    0.1％    5629    33    AAgGAAUUCGGAUGGCCAU    0.1％

5584    25    UAGCAUACUUACcGACAGC    0.2％    5630    33    AAAGAAUUCGaAUGGCCAU    0.6％

26      26    CUCUAGCAUACUUACUGAC    98.6％   5631    33    AAAGAAUUCGGAUGGCCAC    0.1％

5585    26    C0CUAGCAUACUUACUGAu    0.3％    5632    33    AAAGAuUUCGGAUGGCCAU    0.1％

5586    26    CUCUAGCAUgCUUACUGAC    0.1％    5633    33    AAAGgAUUCGaAUGGCCAU    0.1％

5587    26    CUuUAGCAUACUUACUGAC    0.2％    34      34    AGCGACCAAAAGAAUUCGG    98.5％

5588    26    CUaUAGCAUACUUACUGAC    0.1％    5634    34    AGCGACCAAAAGgAUUCGG    0.2％

5589    26    CUCcAGCAUACUUACUGAC    0.3％    5635    34    AGCGACCAAAgGAAUUCGG    0.1％

5590    26    CUCUAaCAUACUUACUGAC    0.1％    5636    34    AGCGACCAAAAGAAUUCGa    0.6％

5591    26    CUCUAGCAUACUUACcGAC.   0.2％    5637    34    AGCGACCAAAAGAuUUCGG    0.1％

27      27    CUAGCAUACUUACUGACAG    98.6％   5638    34    AGCGACCAAAAGgAUUCGa    0.1％

5592    27    CUAGCAUACUUACUGAuAG    0.3％    5639    34    gaCGAuCAAAAGAAUUCGG    0.1％

5593    27    CUAGCAUgCUUACUGACAG    0.1％    35      35    GCGACCAAAAGAAUUCGGA    98.5％

5594    27    uUAGCAUACUUACUGACAG    0.2％    5640    35    GCGACCAAAAGgAUUCGGA    0.2％

5595    27    aUAGCAUACUUACUGACAG    0.1％    5641    35    GCGACCAAAgGAAUUCGGA    0.1％

5596    27    CcAGCAUACUUACUGACAG    0.3％    5642    35    GCGACCAAAAGAAUUCGaA    0.6％

5597    27    CUAaCAUACUUACUGACAG    0.1％    5643    35    GCGACCAAAAGAuUUCGGA    0.1％

5598    27    CUAGCAUACUUACcGACAG    0.2％    5644    35    aCGAuCAAAAGAAUUCGGA    0.1％

28      28    UCUAGCAUACUUACUGACA    98.6％   5645    35    GCGACCAAAAGgAUUCGaA    0.1％

5599    28    UCUAGCAUACUUACUGAUA    0.3％    36      36    CCAAAAGAAUUCGGAUGGC    98.5％

5600    28    UCUAGCAUgCUUACUGACA    0.1％    5646    36    CCAAAAGgAUUCGGAUGGC    0.2％

5601    28    UuUAGCAUACUUACUGACA    0.2％    5647    36    CCAAAgGAAUUCGGAUGGC    0.1％

5602    28    UaUAGCAUACUUACUGACA    0.1％    5648    36    uCAAAAGAAUUCGGAUGGC    0.1％

5603    28    UCcAGCAUACUUACUGACA    0.3％    5649    36    CCAAAAGAAUUCGaAUGGC    0.6％

5650    36    CCAAAAGAuUUUCGGAUGG    0.1％    5696   44    AAUUCGGAUGGCCAUuAAU    0.22％

5651    36    CCAAAAGgAUUCGaAUGGC    0.1％    5697   44    gAUUCGGAUGGCCAUCAAU    0.2％

37      37    ACCAAAAGAAUUCGGAUGG    98.5％   5698   44    AAUUCGaAUGGCCAUCAAU    0.6％

5652    37    ACCAAAAGgAUUCGGAUGG    0.2％    5699   44    AAUUCGGAUGGCCAcCAAU    0.1％

5653    37    ACCAAAgGAAUUCGGAUGG    0.1％    5700   44    AAUUCGGAUGGCCAUCAAg    0.1％

5654    37    AUCAAAAGAAUUCGGAUGG    0.1％    5701   44    AuaUCGGAUGGCCAUCAAU    0.1％

5655    37    ACCAAAAGAAUUCGaAUGG    0.6％    5702   44    gAUUCGaAUGGCCAUCAAU    0.1％

5656    37    ACCAAAAGAuUUCGGAUGG    0.1％    45     45    GGGACUCUAGCAUACUUAC    98.1％

5657    37    ACCAAAAGgAUUCGaAUGG    0.1％    5703   45    GGGACUCUAGCAUgCUUAC    0.1％

38      38    GAAUUCGGAUGGCCAUCAA    98.4％   5704   45    GGGACUuUAGCAUACUUAC    0.2％

5658    38    GAAUUCGGAUGGCCAUUAA    0.2％    5705   45    GaGACUCUAGCAUACUUAC    0.4％

5659    38    GgAUUCGGAUGGCCAUCAA    0.2％    5706   45    GGaACUCUAGCAUACUUAC    0.6％

5660    38    GAAUUCGaAUGGCCAUCAA    0.6％    5707   45    GGGACUaUAGCAUACUUAC    0.1％

5661    38    GAAUUCGGAUGCCAcCCAA    0.1％    5708   45    GGGACUCcAGCAUACUUAC    0.3％

5662    38    GAuUUCGGAUGGCCAUCAA    0.1％    5709   45    GGGACUCUAaCAUACUUAC    0.1％

5663    38    GgAUUCGaAUGGCCAUCAA    0.1％    46     46    ACGGGACUCUAGCAUACUU    98.0％

39      39    UUCGGAUGGCCAUCAAUUA    98.3％   5710   46    ACGGGACUCUAGCAUgCUU    0.1％

5664    39    UUCGGAUGGCCAUuAAUUA    0.2％    5711   46    ACGGGACUuUAGCAUACUU    0.2％

5665    39    UUCGaAUGGCCAUCAAUUA    0.7％    5712   46    AaGGGACUCUAGCAUACUU    0.1％

5666    39    UUCGGAUGGCCAUCAAgUA    0.1％    5713   46    ACGaGACUCUAGCAUACUU    0.4％

5667    39    UUCGGAUGGCCAUCAAUag    0.1％    5714   46    ACGGAACUCUAGCAUACUU    0.6％

5668    39    UUCGGAUGGCCACCAAUgA    0.1％    5715   46    ACGGGACUaUAGCAUACUU    0.1％

40      40    AUUCGGAUGGCCAUCAAUU    98.3％   5716   46    ACGGGACUCCAGCAUACUU    0.3％

5669    40    AUUCGGAUGGCCAUuAAUU    0.2％    5717   46    ACGGGACUCUAaCAUACUU    0.1％

5670    40    AUUCGaAUGGCCAUCAAUU    0.7％    47     47    AAACGGGACUCUAGCAUAC    98.0％

5671    40    AUUCGGAUGGCCAUCAAgU    0.1％    5718   47    AAACGGGACUCUAGCAUgC    0.1％

5672    40    AUUCGGAUGGCCAUCAAUa    0.1％    5719   47    AAACGGGACUuUAGCAUAC    0.2％

5673    40    uUUCGGAUGGCCAUCAAUU    0.1％    5720   47    AAAaGGGACUCUAGCAUAC    0.1％

5674    40    AUUCGGAUGGGCCAcCAAUg   0.1％    5721   47    AAACGaGACUCUAGCAUAC    0.4％

41      41    GACUCUAGCAUACUUACUG    98.3％   5722   47    AAACGGaACUCUAGCAUAC    0.6％

5675    41    GACUCUAGCAUgCUUACUG    0.1％    5723   47    AAACGGGACUaUAGCAUAC    0.1％

5676    41    GACUuUAGCAUACUUACUG    0.2％    5724   47    AAACGGGACUCcAGCAUAC    0.3％

5677    41    aACUCUAGCAUACUUACUG    0.6％    5725   47    AAACGGGACUCUAaCAUAC    0.1％

5678    41    GACUaUAGCAUACUUACUG    0.1％    48     48    CGGGACUCUAGCAUACUUA    98.0％

5679    41    GACUCcAGCAUACUUACUG    0.3％    5726   48    CGGGACUCUAGCAUgCUUA    0.1％

5680    41    GACUCUAaCAUACUUACUG    0.1％    5727   48    CGGGACUuUAGCAUACUUA    0.2％

5681    41    GACUCUAGCAUACUUACcG    0.2％    5728   48    aGGGACUCUAGCAUACUUA    0.1％

42      42    AGAAUUCGGAUGGCCAUCA    98.3％   5729   48    CGaGACUCUAGCAUACUUA    0.4％

5682    42    AGAAUUCGGAUGGCCAUuA    0.2％    5730   48    CGGaACUCUAGCAUACUUA    0.6％

5683    42    AGgAUUCGGAUGGCCAUCA    0.2％    5731   48    GGGGACUaUAGCAUACUUA    0.1％

5684    42    gGAAUUCGGAUGGCCAUCA    0.1％    5732   48    CGGGACUCcAGCAUACUUA    0.3％

5685    42    AGAAUUCGaAUGGCCAUCA    0.6％    5733   48    CGGGACUCUAaCAUACUUA    0.1％

5686    42    AGAAUUCGGAUGGCCAcCA    0.1％    49     49    AACGGGACUCUAGCAUACU    98.0％

5687    42    AGAuUUCGGAUGGCCAUCA    0.1％    5734   49    AACGGGACUCUAGCAUgCU    0.1％

5688    42    AGgAUUUGaAUGGCCAUCA    0.1％    5735   49    AACGGGACUuUAGCAUACU    0.2％

43      43    AAGAAUUCGGAUGGCCAUC    98.3％   5736   49    AAaGGGACUCUAGCAUACU    0.1％

5689    43    AAGAAUUCGGAUGGCCAUU    0.2％    5737   49    AACGaGACUCUAGCAUACU    0.4％

5690    43    AAGgAUUCGGAUGGCGAUC    0.2％    5738   49    AACGGaACUCUAGCAUACU    0.6％

5691    43    AgGAAUUCGGAUGGCCAUC    0.1％    5739   49    AACGGGACUaUAGCAUACU    0.1％

5692    43    AAGAAUUCGaAUGGCCAUC    0.6％    5740   49    AACGGGACUCcAGCAUACU    0.3％

5693    43    AAGAAUUCGGAUGGCCACC    0.1％    5741   49    AACGGGACUCUAaCAUACU    0.1％

5694    43    AAGAuUUCGGAUGGCCAUC    0.1％    50     50    GGACUCUAGCAUACUUACU    97.6％

5695    43    AAGgADDUGaAUGGCCAUC    0.1％    5742    50    GGACUCUAGCAUgCUUACU    0.2％

44      44    AAUUCGGAUGGCCAUCAAU    98.3％   5743   50    GGACUuUAGCAUACUUACU    0.2％

5744    50    aGACUCUAGCAUACUUACU    0.4％    5787    61    GAAACGAAAACGGaACUCU    0.5％

5745    50    GaACUCUAGCAUACUUACU    0.6％    5788    61    GAAACGAAAACGGGACUaU    0.1％

5746    50    GGACUaUAGCAUACUUACU    0.1％    5789    61    GAAACGAAAACGGGACUCC    0.3％

5747    50    GGACUCcAGCAUACUUACU    0.3％    5790    61    GAAACGgAAACGaGACUCU    0.1％

5748    50    GGACUCUAaCAUACUUACU    0.1％    5791    61    GAAACGgAAACGGaACUCU    0.1％

5749    50    GGACUCUAGCAUACUUACc    0.2％    62      62    AAACGAAAACGGGACUCUA    95.5％

51      51    ACGAAACGAAAACGGGACU    95.9％   5792    62    AAACGgAAACGGGACUCUA    2.7％

5750    51    AUGAAACGgAAACGGGACU    2.9％    5793    62    AAACGgAAACGGGACUuUA    0.2％

5751    51    AUGAAACGAAAAaGGGACU    0.1％    5794    62    aAACGAAAAaGGGACUCUA    0.1％

5752    51    AUGAAACGAAAACGaGACU    0.3％    5795    62    AAACGAAAACGaGACUCUA    0.3％

5753    51    AUGAAACGAAAACGGaACU    0.5％    5796    62    AAACGAAAACGGaACUCUA    0.5％

5754    51    AUGAAACGgAAACGaGACU    0.1％    5797    62    AAACGAAAACGGGACUaUA    0.1％

5755    51    AUGAAACGgAAACGGaACU    0.1％    5798    62    AAACGAAAACGGGACUCcA    0.3％

52      52    GAAAUGGAUGAUGGCAAUG    95.8％   5799    62    AAACGgAAACGaGACUCUA    0.1％

5756    52    GAAAUGGAUGAUGGCgAUG    4.1％    5800    62    AAACGgAAACGGaACUCUA    0.1％

5757    52    GAAGUGGAUGAUGGCAAUG    0.1％    63      63    AACGAAAACGGGACUCUAG    95.4％

53      53    UGGAUGAUGGCAAUGAAAU    95.8％   5801    63    AACGgAAACGGGACUCUAG    27％

5758    53    UGGAUGAUGGCAAUGAgAU    0.1％    5802    63    AACGgAAACGGGACUuUAG    0.2％

5759    53    UGGAUGAUGGCgAUGAAAU    4.1％    5803    63    AACGAAAAaGGGACUCUAG    0.1％

54      54    UGAAAUGGAUGAUGGCAAU    95.8％   5804    63    AACGAAAACGaGACUCUAG    0.3％

5760    54    UGAAAUGGAUGAUGGCgAU    4.1％    5805    63    AACGAAAACGGaACUCUAG    0.5％

5761    54    UGAAgUGGAUGAUGGCAAU    0.1％    5806    63    AACGAAAACGGGACUaUAG    0.1％

55      55    GGAUGAUGGCAAUGAAAUA    95.8％   5807    63    AACGAAAACGGGACUCCAG    0.3％

5762    55    GGAUGAUGGCAAUGAgAUA    0.1％    5808    63    AACGAAAACGGGACUCUAa    0.1％

5763    55    GGAUGAUGGCgAUGAAAUA    4.1％    5809    63    AACGgAAACGaGACUCUAG    0.1％

56      56    UGAAACGAAAACGGGACUC    95.8％   5810    63    AACGgAAACGGaACUCUAG    0.1％

5764    56    UGAAACGgAAACGGGACUC    2.7％    64      64    GAAAACGGGACUCUAGCAU    95.4％

5765    56    UGAAACGgAAACGGGACUu    0.2％    5811    64    GgAAACGGGACUCUAGCAU    2.7％

5766    56    UGAAACGAAAAaGGGACUC    0.1％    5812    64    GgAAACGGGACUuUAGCAU   0.2％

5767    56    UGAAACGAAAACGaGACUC    0.3％    5813    64    GAAAAaGGgACUCUAGCAU    0.1％

5768    56    UGAAACGAAAACGGaACUC    0.5％    5814    64    GAAAACGaGACUCUAGCAU    0.3％

5769    56    UGAAACGAAAACGGGACUa    0.1％    5815    64    GAAAACGGaACUCUAGCAU    0.55％

5770    56    UGAAACGgAAACGaGACUC    0.1％    5816    64    GAAAACGGGACUaUAGCAU    0.1％

5771    56    UGAAACGgAAACGGaACUC    0.1％    5817    64    GAAAACGGGACUCcAGCAU    0.3％

57      57    AAAUGGAUGAUGGCAAUGA    95.8％   5818    64    GAAAACGGGACUCUAaCAU    0.1％

5772    57    AAAUGGAUGAUGGCgAUGA    4.1％    5819    64    GgAAACGaGACUCUAGCAU    0.1％

5773    57    AAgUGGAUGAUGGCAAUGA    0.1％    5820    64    GgAAACGGaACUCUAGCAU    0.1％

58      58    AUGGAUGAUGGCAAUGAAA    95.7％   65      65    ACGAAAACGGGACUCUAGG    95.4％

5774    58    AUGGAUGAUGGCAAUGAgA    0.1％    5821    65    ACGgAAACGGGACUCUAGC    2.7％

5775    58    AUGGAUGAUGGCgAUGAAA    4.1％    5822    65    ACGgAAACGGGACUuUAGC    0.2％

5776    58    gUGGAUGAUGGCAAUGAAA    0.1％    5823    65    ACGAAAAaGGGACUCUAGC    0.1％

59      59    AAUGGAUGAUGGCAAUGAA    95.7％   5824    65    ACGAAAACGaGACUCUAGC    0.3％

5777    59    AAUGGAUGAUGGCAAUGAg    0.1％    5825    65    ACGAAAACGGaACUCUAGC    0.5％

5778    59    AAUGGAUGAUGGCgAUGAA    4.1％    5826    65    ACGAAAACGGGACUaUAGC    0.1％

5779    59    AgUGGAUGAUGGCAAUGAA    0.1％    5827    65    ACGAAAACGGGACUCcAGC    0.3％

60      60    AUGAAAUGGAUCAUGGCAA    95.7％   5828    65    ACGAAAACGGGACUCUAaC    0.1％

5780    60    AUGAAAUGGAUGAUGGCgA    4.1％    5829    65    ACGgAAACGaGACUCUAGC    0.1％

5781    60    AUGAAgUGGAUGAUGGCAA    0.1％    5830    65    ACGgAAACGGaACUCUAGC    0.1％

5782    60    gUGAAAUGGAUGAUGGCAA    0.1％    66      66    CGAAAACGGGACUCUAGCA    95.4％

61      61    GAAACGAAAACGGGACUCU    95.5％   5831    66    CGgAAACGGGACUCUAGCA    2.7％

5783    61    GAAACGgAAACGGGACUCU    2.7％    5832    66    CGgAAACGGGACUuUAGCA    0.2％

5784    61    GAAACGgAAACGGGACUUU    0.2％    5833    66    CGAAAAaGGGACUCUAGCA    0.1％

5785    61    GAAACGAAAAaGGGACUCU    0.1％    5834    66    CGAAAACGaGACUCUUAGCA   0.3％

5786    61    GAAACGAAAACGaGACUCU    0.3％    5835    66    CGAAAACGGaAACUCUAGCA   0.5％

5836    66    CGAAAACGGGACUaUAGCA    0.1％    5885    71    GGUUAAAACAcGGAACCUU    0.1％

5837    66    CGAAAACGGGACUCcAGCA    0.3％    5886    71    GGcUAAAgCAUGGAACCUU    0.2％

5838    66    CGAAAACGGGACUCUAaCA    0.1％    5887    71    GGUUAAAgCAcGGAACCUU    0.1％

5839    66    CGgAAACGaGACUCUAGCA    0.1％    5888    71    GaUUAAAACAcGGAACCUU    2.2％

5840    66    CGgAAACGgaACUCUAGCA    0.1％    5889    71    GaUUAAAACAcGGgACCUU    0.1％

67      67    AAAACGGGACUCUAGCAUA    95.3％   72      72    AGGUUAAAACAUGGAACCU    94.8％

5841    67    AAAACGGGACUCUAGCAUg    0.1％    5890    72    AGGUUAAAACAUGGAACuU    0.1％

5842    67    gAAACGGGACUCUAGCAUA    2.7％    5891    72    AGGUUAAAACAUGGgACCU    1.2％

5843    67    gAAACGGGACUUUAGCAUA    0.2％    5892    72    AGGUUgAAACAUGGAACCU    0.3％

5844    67    AAAAaGGGACUCUAGCAUA    0.1％    5893    72    AGaUUAAAACAUGGAACCU    0.4％

5845    67    AAAACGaGACUCUAGCAUA    0.3％    5894    72    AGGUUAAAAaAUGGAACCU    0.4％

5846    67    AAAACGGaACUCUAGCAUA    0.5％    5895    72    AGGUUAAAACAcGGAACCU    0.1％

5847    67    AAAACGGGACUaUAGCAUA    0.1％    5896    72    AGGcUAAAgCAUGGAACCU    0.2％

5848    67    AAAACGGGACUCCAGCAUA    0.3％    5897    72    AGGUUAAAgCAcGGAACCU    0.1％

5849    67    AAAACGGGACUCUAaCAUA    0.1％    5898    72    AGaUUAAAACAcGGAACCU    2.2％

5850    67    gAAACGaGACUCUAGCAUA    0.1％    5899    72    AGaUUAAAACAcGGgACCU    0.1％

5851    67    gAAACGGaACUCUAGCAUA    0.1％    73      73    CUCGCACUCGCGAGAUACU    94.5％

68      68    GAAAGGUUAAAACAUGGAA    94.9％   5900    73    CUCGCACUCGCGAGAUAuU    1.4％

5852    68    GAAAGGUUAAAACAUGGgA    1.2％    5901    73    CUCGCACUCGuGAGAUACU    0.1％

5853    68    GAAAGGUUgAAACAUGGAA    0.3％    5902    73    CUCGCAuUCGCGAGAUACU    0.1％

5854    68    GAAAGaUUAAAACAUGGAA    0.4％    5903    73    uUCGCACUCGCGAGAUACU    0.1％

5855    68    GAAAGGUUAAAAaAUGGAA    0.4％    5904    73    CcCGCACUCGCGAGAUACU    2.0％

5856    68    GAAAGGUUAAAACAcGGAA    0.1％    5905    73    CUCGCACaCGCGAGAUACU    0.6％

5857    68    GAAAGGcUAAAgCAUGGAA    0.2％    5906    73    CUCGCACcCGCGAGAUACU    0.5％

5858    68    GAAAGGUUAAAgCACGGAA    0.1％    5907    73    CUCGCACUCGCGAaAUACU    0.1％

5859    68    GAAAGaUUAAAACACGGAA    2.2％    5908    73    CUCGCACUCGCGgaAUACU    0.1％

5860    68    GAAAGaUUAAAACAcGGgA    0.1％    5909    73    UUCGCACaCGCGAGAUACU    0.1％

69      69    AAAGGUUAAAACAUGGAAC    94.9％   5910    73    CcCGCACgCGCGAGAUACU    0.2％

5861    69    AAAGGUUAAAACAUGGgAC    1.2％    5911    73    CUCGCACUguCGAGAUACU    0.1％

5862    69    AAAGGUUgAAACAUGGAAC    0.3％    74      74    UCUCGCACUCGCGAGAUAC    94.5％

5863    69    AAAGaUUAAAACAUGGAAC    0.4％    5912    74    UCUCGCACUCGCGAGAUAu    1.4％

5864    69    AAAGGUUAAAAaAUGGAAC    0.4％    5913    74    UCUCGCACUCGuGAGAUAC    0.1％

5865    69    AAAGGUUAAAACACGGAAC    0.1％    5914    74    UCUCGCAUUCGCGAGAUAC    0.1％

5866    69    AAAGGcUAAAgCAUGGAAC    0.2％    5915    74    UuUCGCACUCGCGAGAUAC    0.1％

5867    69    AAAGGUUAAAgCAcGGAAC    0.1％    5916    74    UCcCGCACUCGCGAGAUAC    2.0％

5868    69    AAAGaUUAAAACAcGGAAC    2.2％    5917    74    UCUCGCACaCGCGAGAUAC    0.6％

5869    69    AAAGaUUAAAACAcGGgAC    0.1％    5918    74    UCUCGCACcCGCGAGAUAC    0.5％

70      70    AAGGUUAAAACAUGGAACC    94.8％   5919    74    UCUCGCACUCGCGAaAUAC    0.1％

5870    70    AAGGUUAAAACAUGGAACu    0.1％    5920    74    UCUCGCACUCGCGgaAUAC    0.1％

5871    70    AAGGUUAAAACAUGGgACC    1.2％    5921    74    UuUCGCACaCGCGAGAUAC    0.1％

5872    70    AAGGUUgAAACAUGGAACC    0.3％    5922    74    UCcCGCACgCGCGAGAUAC    0.2％

5873    70    AAGaUUAAAACAUGGAACC    0.4％    5923    74    UCUCGCACUguCGAGAUAC    0.1％

5874    70    AAGGUUAAAAaAUGGAACC    0.4％    75      75    UAAAAGCAGUUAGAGGUGA    94.3％

5875    70    AAGGUAAAACACGGGAACC    0.1％    5924    75    UAAAAGCUGUUAGAGGUGA    0.3％

5876    70    AAGGcUAAAgCAUGGAACC    0.2％    5925    75    UgAAAGCAGUUAGAGGUGA    0.2％

5877    70    AAGGUUAAAgCAcGGAACC    0.1％    5926    75    UAAAgGCAGUUAGgGGUGA    0.1％

5879    70    AAGaUUAAAACACgGAACC    2.2％    5927    75    UAAAAGCAGUcAGAGGUgA    0.4％

5879    70    AAGaUUAAAACAcGGgACC    0.1％    5928    75    UAAAAGCAGUUAGAGGaGA    0.7％

71      71    GGUUAAAACAUGGAACCUU    94.8％   5929    75    UAAAAuCAgUUAGAGGUGA    0.1％

5880    71    GGUUAAACAUGGGAACuUU    0.1％    5930    75    UAAAAGCAGUcAGgGGUGA    0.1％

5881    71    GGUUAAAACAUGGgACCUU    1.2％    5931    75    UAAAgGCAGUccGAGGUGA    2.2％

5882    71    GGUUgAAACAUGGAACCUU    0.3％    76      76    UCGGAUGGCCAUCAAUUAA    94.2％

5883    71    GaUUAAAACAUGGAACCUU    0.4％    5932    76    UCGGAUGGCcAUCAAUUAg    3.9％

5884    71    GGUUAAAAaAUGGAACCUU    0.4％    5933    76    UCGGAUGGCCAUuAAUUAA    0.2％

5934    76    UCGaAUGGCCAUCAAUUAA    0.7％    5979    85    ACUUAGGgUGAAAUGGAUG     0.1％

5935    76    UCGGAUGGCCAUCAAgUAA    0.1％    5980    85    ACUcAGGAUGAAAUGGAUG     0.1％

5936    76    UCGGAUGGCCAUCAAUagg    0.1％    5981    85    ACUUAGaAUGAAAUGGAUG     2.1％

5937    76    UCGGAUGGCCAcCAAUgAg    0.1％    5982    85    uCUUAGaAUGAAAUGGAUG     2.3％

77      77    AGGAUGAAAUGGAUGAUGG    94.0％   86      86    GUUGCAUACAUGUUAGAGA     93.8％

5938    77    AGGAUGAAgUGGAUGAUGG    0.1％    5983    86    GUUGCAUACAUGUUgGAGA     0.3％

5939    77    AGGgUGAAAUGGAUGAUGG    0.1％    5984    86    GUUGCgUACAUGUUAGAGA     1.5％

5940    77    AGaAUGAAAUGGAUGAUGG    5.8％    5985    86    aUUGCAUACAUGUUAGAGA     0.1％

78      78    GGAUGAAAUGGAUGAUGGC    94.0％   5986    86    GUcGCAUACAUGUUAGAGA     0.3％

5941    78    GGAUGAAgUGGAUGAUGGC    0.1％    5987    86    GUUGCAUACAUGUUAGAaA     0.1％

5942    78    GGgUGAAAUGGAUGAUGGC    0.1％    5988    86    GUgGCAUACAUGUUgGAGA     0.2％

5943    78    GaAUGAAAUGGAUGAgGGC    5.8％    5989    86    GUUGCAUACAUGUUgGAaA     1.2％

79      79    UUAGGAUGAAAUGGAUGAU    93.9％   5990    86    GUgGCAUACAUGUUggAaA     0.3％

5944    79    UUAGGAUGAAgUGGAUGAU    0.1％    87      87    UAAAACAUGGAACCUUUGG     93.8％

5945    79    UUAGGgUGAAAUGGAUGAU    0.1％    5991    87    UAAAACAUGGAACuUUUGG     0.1％

5946    79    UcAGGAUGAAAUGGAUGAU    0.1％    5992    87    UAAAACAUGGgACCUUUGG     1.2％

5947    79    UUAGaAUGAAAUGGAUGAU    4.5％    5993    87    UAAAgCAUGGAACCUUUGG     0.2％

5948    79    UcAGaAgGAAAUGGAUGAU    1.3％    5994    87    UgAAACAUGGAACCUUUGG     0.3％

80      80    AUGGUUGCAUACAUGUUAG    93.9％   5995    87    UAAAAaAUGGAACCUUUGG     0.4％

5949    80    AUGGUUGCAUACAUGUUgG    1.5％    5996    87    UAAAACAcGGAACCUUUGG     2.2％

5950    80    AUGGUUGCgUACAUGUUAG    1.5％    5997    87    UAAAACAUGGAACCUUcGG     1.2％

5951    80    AUGaUUGCAUACAUGUUAG    0.1％    5998    87    UAAAACAUGGAACCUUnGG     0.1％

5952    80    AUGGUcGCAUACAUGUUAG    0.3％    5999    87    UAAAACAUGGAACCUUUaG     0.1％

5953    80    AUGGUgGCAUACAUGUUgG    0.5％    6000    87    UAAAACAcGGgACCUUUGG     0.1％

5954    80    AUGGUgGCAUAuAUGUUgG    2.0％    6001    87    UAAAgCACGGAACCUUUGG     0.1％

81      81    UAGGAUGAAAUGGAUGAUG    93.9％   6002    87    UAAAACAcGGAACCUUcGG     0.1％

5955    81    UAGGAUGAAgUGGAUGAUG    0.1％    88      88    UUAAAACAUGGAACCUUUG     93.8％

5956    81    UAGGgUGAAAUGGAUGAUG    0.1％    6003    88    UUAAAACAUGGAACuUUUG     0.1％

5957    81    UAGGAUGAAAUGGAUGAUG    0.1％    6004    88    UUAAAACAUGGgACCUUUG     1.2％

5958    81    UAGaAUGAAAUGGAUGAUG    4.5％    6005    88    UUgAAACAUGGAACCUUUG     0.3％

5959    81    cAGaAUGAAAUGGAUGAUG    1.3％    6006    88    UUAAAAaAUGGAACCUUUG     0.4％

82      82    UGGUUGCAUACAUGUUAGA    93.9％   6007    88    UUAAAACAcGGAACCUUUG     2.2％

5960    82    UGGUUGCAUACAUGUUgGA    1.5％    6008    88    UUAAAACAUGGAACCUUcG     1.2％

5961    82    UGGUUGCgUACAUGUUAGA    1.5％    6009    88    UUAAAACAUGGAACCUUnG     0.1％

5962    82    UGaUUGCAUACAUGUUAGA    0.1％    6010    88    UUAAAACAUGGAACCUUUa     0.1％

5963    82    UGgUcGCAUACAUGUUAGA    0.3％    6011    88    UUAAAgCAUGGAACCUUUG     0.2％

5964    82    UGGggGCAUACAUGUUgGA    0.5％    6012    88    UUAAAACAcGGgACCUUUG     0.1％

5965    82    UGGUgGCAUAuAUGUUgGA    2.1％    6013    88    UUAAAgCAcGGAACCUUUG     0.1％

83      83    CUUAGGAUGAAAUGGAUGA    93.9％   6014    88    UUAAAACAcGGAACCUUcG     0.1％

5966    83    CUUAGGAUGAAgUGGAUGA    0.1％    89      89    GGUUGCAUACAUGUUAGAG     93.8％

5967    83    CUUAGGgUGAAAUGGAUGA    0.1％    6015    89    GGUUGCAUACAUGUUgGAG     0.3％

5968    83    CUcAGGAUGAAAUGGAUGA    0.1％    6016    89    GGUUGCgUACAUGUUAGAG     1.5％

5969    83    CUUAGaAUGAAAUGGAUGA    4.5％    6017    89    GaUUGCAUACAUGUUAGAG     0.1％

5970    83    CUcAGaAUGAAAUGGAUGA    1.3％    6018    89    GGUcGCAUACAUGUUAGAG     0.3％

84      84    UUGCAUACAUGUUAGAGAG    93.9％   6019    89    GGUUGCAUACAUGUUAGAa     0.1％

5971    84    UUGCAUACAUGUUgGAGAG    0.3％    6020    89    GGUgGCAUACAUGUUgGAG     0.2％

5972    84    UUGCgUACAUGUUAGAGAG    1.5％    6021    89    GGUUGCAUACAUGUUGGAa     1.2％

5973    84    UcGCAUACAUGUUAGAGAG    0.3％    6022    89    GGUgGCAUACAUGUUgGAa     0.3％

5974    84    UUGCAUACAUGUUAGAaAG    0.1％    90      90    UGAUGGUUGCAUACAUGUU     93.7％

5975    84    UgGCAUACAUGUUgGAGAG    0.2％    6023    90    UGAUGGUUGCgUACAUGUU     1.5％

5976    84    UUGCAUACAUGUUgGAaAG    1.2％    6024    90    UaAUGGUUGCAUACAUGUU     1.7％

5977    84    UgGCAUACAUGUUgGAaAG    0.3％    6025    90    UGAUGaUUGCAUACAUGUU     0.1％

85      85    ACUUAGGAUGAAAUGGAUG    93.9％   6026    90    UGAUGGUcGCAUACAUGUU     0.3％

5978    85    ACUUAGGAUGAAgUGGAUG    0.1％    6027    90    UGAUGGUgGCAUACAUGUU     0.1％

6028    90    UaAUGGUgGCAUACAUGUU    0.4％    6075    97    UCACUUAGGAUGAAgUGGA    0.1％

6029    90    UaAUGGUgGCAUauAUGUU    2.0％    6076    97    UCACUUAGGgUGAAAUGGA    0.1％

91      91    AUGAGAAUACUUGUAAGGG    93.7％   6077    97    UuACUUAGGAUGAAAUGGA    0.2％

6030    91    AUGAGAAUACUUGUgAGGG    0.2％    6078    97    gCACUUAGGAUGAAAUGGA    0.4％

6031    91    AUGAGAAUACUcGUAAGGG    1.3％    6079    97    UCACUcAGGAUGAAAUGGA    0.1％

6032    91    AUGAGAAUACUUGUAAGaG    2.6％    6080    97    UCACUUAGaAUGAAAUGGA    2.1％

6033    91    AUGAGAAUACUUGUgAGaG    2.0％    98      98    AACAUGGAACCUUUGGCCC    93.1％

6034    91    AUGAcAAUACUUGUgAGaG    0.1％    6081    98    AACAUGGAACCUUUGGuCC    1.1％

92      92    UGAGAAUACUUGUAAGGGG    93.7％   6082    98    AACAUGGAACUUUUGGCCC    0.1％

6035    92    UGAGAAUACUUGUgAGGGG    0.2％    6083    98    AACAUGGgACCUUUGGCCC    1.1％

6036    92    UGAGAAUACUcGUAAGGGG    1.3％    6084    98    AgCAUGGAACCUUUGGCCC    0.2％

6037    92    UGAGAAUACUUGUAAGaGG    2.6％    6085    98    AACAUGGgACCUUUGGuCC    0.1％

6038    92    UGAGAAUACUUGUgAGaGG    2.0％    6086    98    AAaAUGGAACCUUUGGCCC    0.4％

6039    92    UGAcAAUACUUGUgAGaGG    0.1％    6087    98    AACAcGGAACCUUUGGCCC    2.2％

93      93    CACUUAGGAUGAAAUGGAU    93.7％   6088    98    AACAUGGAACCUUnGGCCC    0.1％

6040    93    CACUUAGGAUGAAgUGGAU    0.1％    6089    98    AACAUGGAACCUUUaGCCC    0.1％

6041    93    CACUUAGGgUGAAAUGGAU    0.1％    6090    98    AACAcGGgACCUUUGGCCC    0.1％

6042    93    UACUUAGGAUGAAAUGGAU    0.2％    6091    98    AACAUGGAACCUUcGGuCC    1.2％

6043    93    CACUcAGGAUGAAAUGGAU    0.1％    6092    98    AgCAcGGAACCUUUGGCCC    0.1％

6044    93    CACUUAGaAUGAAAUGGAU    2.1％    6093    98    AACAcGGAACCUUcGGCCC    0.1％

6045    93    CuCUUAGaAUGAAAUGGAU    2.3％    99      99    AAACAUGGAACCUUUGGCC    93.1％

94      94    GUUAAAACAUGGAACCUUU    93.7％   6094    99    AAACAUGGAACCUUUGGuC    1.1％

6046    94    GUUAAAACAUGGAACUUUU    0.1％    6095    99    AAACAUGGAACuUUUGGCC    0.1％

6047    94    GUUAAAACAUGGgACCUUU    1.2％    6096    99    AAACAUGGgACCUUUGGCC    1.1％

6048    94    GUUgAAACAUGGAACCUUU    0.3％    6097    99    AAgCAUGGAACCUUUGGCC    0.2％

6049    94    aUUAAAACAUGGAACCUUU    0.2％    6098    99    AAACAUGGgACCUUUGGUC    0.1％

6050    94    GUUAAAAaAUGGAACCUUU    0.4％    6099    99    AAAaAUGGAACCUUUGGCC    0.4％

6051    94    GUUAAAACAcGGAACCUUU    0.1％    6100    99    AAACAcGGAACCUUUGGCC    2.2％

6052    94    GUUAAAACAUGGAACCUUc    1.0％    6101    99    AAACAUGGAACCUUnGGCC    0.1％

6053    94    GUUAAAACAUGGAACCUUn    0.1％    6102    99    AAACAUGGAACCUUUaGCC    0.1％

6054    94    GcUAAAgCAUGGAACCUUU    0.2％    6103    99    AAACAcGGgACCUUUGGCC    0.1％

6055    94    GUUAAAgCAcGGAACCUUU    0.1％    6104    99    AAACAUGGAACCUUcGGUC    1.2％

6056    94    aUUAAAACAcGGAACCUUU    2.1％    6105    99    AAgCACGGAACCUUUGGCC    0.1％

6057    94    aUUAAAACAUGGAACCUUc    0.2％    6106    99    AAACAcGGAACUUcGGGCC    0.1％

6058    94    aUUAAAACAcGGgACCUUU    0.1％    100     100   CAAGCUGUGGAUAUAUGCA    92.9％

95      95    UUGAUGGUUGCAUACAUGU    93.5％   6107    100   CAAGCUGUGGAUAUAUGuA    0.1％

6059    95    UUGAUGGUUGCgUACAUGU    1.5％    6108    100   CAgGCUGUGGAUAUAUGCA    0.2％

6060    95    cUGAUGGUUGCAUACAUGU    0.2％    6109    100   CAAGCaGUGGAUAUAUGCA    0.1％

6061    95    UUaAUGGUUGCAUACAUGU    1.7％    6110    100   CAAGCcGUGGAUAUAUGCA    0.5％

6062    95    UUGAUGaUUGCAUACAUGU    0.1％    6111    100   CAAGCUGUaGAUAUAUGCA    2.8％

6063    95    UUGAUGGUcGCAUACAUGU    0.3％    6112    100   CAAGCUGUGaAUAUAUGCA    0.1％

6064    95    cUGAUGGUgGCAUACAUGU    0.1％    6113    100   CAAGCUGUGGAaAUAUGCA    0.2％

6065    95    UUaAUGGUgGCAUACAUGU    0.4％    6114    100   CAAGCUGUGGACAUAUGCA    2.6％

6066    95    UUaAUGGUgGCAUAuAUGU    2.0％    6115    100   CAAGCcGUGGAUAUAUGuA    0.1％

96      96    GAUGGUUGCAUACAUGUUA    93.4％   6116    100   CAAGCcGUGGgUAUAUGCA    0.1％

6067    96    GAUGGUUGCAUACAUGUUg    0.3％    6117    100   CAAGCaGUaGAUAUAUGCA    0.2％

6068    96    GAUGGUUGCgUACAUGUUA    1.5％    6118    100   CAAGCCGUGGAUAUuUGCA    0.1％

6069    96    aAUGGUUGCAUACAUGUUA    0.5％    101     101   AAGCUGUGGAUAUAUGCAA    92.9％

6070    96    GAUGaUUGCAUACAUGUUA    0.1％    6119    101   AAGCUGUGGAUAUAUGuAA    0.1％

6071    96    GAUGGUcGCAUACAUGUUA    0.3％    6120    101   AgGCUGUGGAUAUAUGCAA    0.2％

6072    96    aAUGGUUGCaUACAUGUUg    1.2％    6121    101   AAGCaGUGGAUAUAUGCAA    0.1％

6073    96    GAUGGUgGCAUACAUGUUG    0.1％    6122    101   AAGCCGUGGAUAUAUGCAA    0.5％

6074    96    aAUGGUgGCAUACAUGUUg    0.4％    6123    101   AAGCUGUaGAUAUAUGCAA    2.8％

97      97    UCACUUAGGAUGAAAUGGA    93.3％   6124    101   AAGCUGUGaAUAUAUGCAA    0.1％

6125    101    AAGCUGUGGAaAUAUGCAA    0.2％    6174    106    GgUGAAAUGGAUGAUGGCA    0.1％

6126    101    AAGCUGUGGAcAUAUGCAA    2.6％    6175    106    aAUGAAAUGGAUGAUGGCA    3.4％

6127    101    AAGCcGUGGAUAUAUGuAA    0.1％    6176    106    aAUGAAAUGGAUGAUGGCg    2.3％

6128    101    AAGCcGUGGgUAUAUGCAA    0.1％    107     107    AACAAGCUGUGGAUAUAUG    91.3％

6129    101    AAGCaGUaGAUAUAUGCAA    0.2％    6177    107    AACAgGCUGUGGAUAUAUG    0.2％

6130    101    AAGCcGUGGAUAUuUGCAA    0.1％    6178    107    AgCAAGCUGUGGAUAUAUG    1.7％

102     102    AAAACAUGGAACCUUUGGC    92.8％   6179    107    AACAAGCaGUGGAUAUAUG    0.1％

6131    102    AAAACAUGGAACCUUUGGu    1.1％    6180    107    AACAAGCcGUGGAUAUAUG    0.4％

6132    102    AAAACAUGGAACuUUUGGC    0.1％    6181    107    AACAAGCUGUaGAUAUAUG    0.3％

6133    102    AAAACAUGGgACCUUUGGC    1.1％    6182    107    AACAAGCUGUGGAcAUAUG    2.6％

6134    102    AAAgCAUGGAACCUUUGGC    0.2％    6183    107    AgCAAGCcGUGGAUAUAUG    0.2％

6135    102    gAAACAUGGAACCUUUGGC    0.3％    6184    107    AgCAAGCUGUaGAUAUAUG    2.5％

6136    102    AAAACAUGGgACCUUUGGu    0.1％    6185    107    AgCAAGCUGUGaAUAUAUG    0.1％

6137    102    AAAAaAUGGAACCUUUGGC    0.4％    6186    107    AgCAAGCUGUGGAaAUAUG    0.2％

6138    102    AAAACAcGGAACCUUUGGC    2.2％    6187    107    AgCAAGCcGUGGgUAUAUG    0.1％

6139    102    AAAACAUGGAACCUUnGGC    0.1％    6188    107    AACAAGCaGUaGAUAUAUG    0.2％

6140    102    AAAACAUGGAACCUUUaGC    0.1％    6189    107    AgCAAGCcGUGGAUAUuUG    0.1％

6141    102    AAAACAcGGgACCUUUGGC    0.1％    108     108    GAACAAGCUGUGGAUAUAU    91.3％

6142    102    AAAACAUGGAACCUUcGGu    1.2％    6190    108    GAACAgGCUGUGGAUAUAU    0.2％

6143    102    AAAgCAcGGAACCUUUGGC    0.1％    6191    108    GAgCAAGCUGUGGAUAUAU    1.7％

6144    102    AAAACAcGGAACCUUcGGC    0.1％    6192    108    GAACAAGCaGUGGAUAUAU    0.1％

103     103    GUAAUGAAACGAAAACGGG    92.6％   6193    108    GAACAAGCcGUGGAUAUAU    0.4％

6145    103    GUAAUGAAACGgAAACGGG    2.7％    6194    108    GAACAAGCUGUaGAUAUAU    0.3％

6146    103    GUgAUGAAACGAAAACGGG    3.3％    6195    108    GAACAAGCUGUGGAcAUAU    2.6％

6147    103    GUgAUGAAACGgAAACGGG    0.2％    6196    108    GAgCAAGCcGUGGAUAUAU    0.2％

6148    103    GUAAUGAAACGAAAAaGGG    0.1％    6197    108    GAgCAAGCUGUaGAUAUAU    2.5％

6149    103    GUAAUGAAACGAAAACGaG    0.3％    6198    108    GAgCAAGCUGUGaAUAUAU    0.1％

6150    103    GUAAUGAAACGAAAACGGa    0.4％    6199    108    GAgCAAGCUGUGGAaAUAU    0.2％

6151    103    GUAAUGAAACGgAAACGaG    0.1％    6200    108    GAgCAAGCcGUGGgUAUAU    0.1％

6152    103    GUAAUGAAACGgAAACGGa    0.1％    6201    108    GAACAAGCaGUaGAUAUAU    0.2％

6153    103    GUgAUGAAACGAAAACGGa    0.1％    6202    108    GAgCAAGCcGUGGAUAUuU    0.1％

104     104    UAAUGAAACGAAAACGGGA    92.6％   109     109    ACAAGCUGUGGAUAUAUGC    91.2％

6154    104    UAAUGAAACGgAAACGGGA    2.7％    6203    109    ACAAGCUGUGGAUAUAUGu    0.1％

6155    104    UgAUGAAACGAAAACGGGA    3.3％    6204    109    ACAgGCUGUGGAUAUAUGC    0.2％

6156    104    UgAUGAAACGgAAACGGGA    0.2％    6205    109    gCAAGCUGUGGAUAUAUGC    1.7％

6157    104    UAAUGAAACGAAAAaGGGA    0.1％    6206    109    ACAAGCaGUGGAUAUAUGC    0.1％

6158    104    UAAUGAAACGAAAACGaGA    0.3％    6207    109    ACAAGCcGUGGAUAUAUGC    0.3％

6159    104    UAAUGAAACGAAAACGGaA    0.4％    6208    109    ACAAGCUGUaGAUAUAUGC    0.3％

6160    104    UAAUGAAACGgAAACGaGA    0.1％    6209    109    ACAAGCUGUGGAcAUAUGC    2.6％

6161    104    UAAUGAAACGgAAACGGaA    0.1％    6210    109    ACAAGCcGUGGAUAUAUGu    0.1％

6162    104    UgAUGAAACGAAAACGGaA    0.1％    6211    109    gCAAGCcGUGGAUAUAUGC    0.2％

105     105    AAUGAAACGAAAACGGGGAC   92.6％   6212    109    gCAAGCUGUaGAUAUAUGC    2.5％

6163    105    AAUGAAACGgAAACGGGAC    2.7％    6213    109    gCAAGCUGUGaAUAUAUGC    0.1％

6164    105    gAUGAAACGAAAACGGGAC    3.3％    6214    109    gCAAGCUGUGGAaAUAUGC    0.2％

6165    105    gAUGAAACGgAAACGGGAC    0.2％    6215    109    gCAAGCcGUGGgUAUAUGC    0.1％

6166    105    AAUGAAACGAAAAaGGGAC    0.1％    6216    109    ACAAGCaGUaGAUAUAUGC    0.2％

6167    105    AAUGAAACGAAAACGaGAC    0.3％    6217    109    gCAAGCcGUGGAUAUuUGC    0.1％

6168    105    AAUGAAACGAAAACGGaAC    0.4％    110     110    UGUACACUCCAGGUGGAGA    90.0％

6169    105    AAUGAAACGgAAACGaGAC    0.1％    6218    110    UGUACACUCCAGGUGGgGA    4.4％

6170    105    AAUGAAACGgAAACGGaAC    0.1％    6219    110    UGUACACaCCAGGUGGAGA    0.1％

6171    105    gAUGAAACGAAAACGGaAC    0.1％    6220    110    UGUACACcCCAGGUGGAGA    0.9％

106     106    GAUGAAAUGGAUGAUGGCA    92.3％   6221    110    UGUACACgCCAGGUGGAGA    0.1％

6172    106    GAUGAAAgGGAUGAUGGCg    1.7％    6222    110    UGUACACUCCAGGcGGAGA    1.3％

6173    106    GAUGAAgUGGAUGAUGGCA    0.1％    6223    110    UGUACACUCCAGGUGGcGA    0.2％

6224    110    UGUACACUCCcGGUGGAGA    0.1％    6233    111    AUGUACACgCCAGGUGGAG    0.1％

6225    110    aGUACACUCCAGGUGGgGA    0.1％    6234    111    AUGUACACUCCAGGcGGAG    1.3％

6226    110    UGUACACUCCAGGaGGgGA    0.2％    6235    111    AUGUACACUCCAGGUGGcG    0.2％

6227    110    UGUACACUCCAGGcGGgGA    0.1％    6236    111    AUGUACACUCCcGGUGGAG    0.1％

6228    110    gGUAuACUCCAGGaGGgGA    0.2％    6237    111    AaGUACACUCCAGGUGGgG    0.1％

6229    110    UGUACACaCCAGGaGGgGA    2.2％    6238    111    AUGUACACUCCAGGaGGgG    0.2％

111     111    AUGUACACUCCAGGUGGAG    90.0％   6239    111    AUGUACACUCCAGGcGGgG    0.1％

6230    111    AUGUACACUCCAGGUGGgG    4.4％    6240    111    AUGUAuACUCCAGGaGGgG    0.2％6231    111    AUGUACACaCCAGGUGGAG    0.1％    6241    111    AUGUACACaCCAGGaGGgG    2.2％

6232    111    AUGUACACcCCAGGUGGAG    0.9％    6242    111    AUGUACACgCCAGGaGGgG    0.1％

表20-2.从表1-2所列甲型流感片段2(PB1)序列得到的保守和小变体19-mer序列。保守序列匹配所列病毒序列的至少89％，变体含有从参考序列的3个或更少核苷酸变化。

Seq   Ref

              匹配序列    ％总数             1188  1188  GAAGUCUGUUCCACCAUU  90.8％

ID   ID

                                           6273  1188  GAAGAUCUGUUuCACCAUU    0.7％

1183  1183  AUGAUGAUGGGCAUGUUCA  96.7％    6274  1188  GAgGAUCUGUUCCACCAUU    0.2％

6243  1183  AUGAUGAUGGGCAUGUUuA  2.7％     6275  1188  GAAaAUCUGUUCCACCAUU    0.1％

6244  1183  AUGAUGAUGGGuAUGUUCA  0.4％     6276  1188  GAAGAcCUGUUCCACCAUU    6.8％

6245  1183  AUGAUGAUGGGuAUGUUuA  0.1％     6277  1188  GAAGAUCUGcUCCACCAUU    0.2％

6246  1183  AUGAUGAUGGGaAUGUUCA  0.1％     6278  1188  GAAGAUCUGUUaCAGCAUU    0.1％

1184  1184  UGAUGAUGGGCAUGUUCAA  96.7％    6279  1188  GAAGAcCUGUUCuACCAUU    0.1％

6247  1184  UGAUGAUGGGCAUGUUuAA  2.7％     6280  1188  aAAGAcCUGUUCCACCAUU    0.1％

6248  1184  UGAUGAUGGGuAUGUUCAA  0.4％     6281  1188  GAAGAcCUGcUCCACCAUU    0.2％

6249  1184  UGAUGAUGGGuAUGUUuAA  0.1％     1189  1189  AAGAUCUGUUCCACCAUUG    90.7％

6250  1184  UGAUGAUGGGaAUGUUCAA  0.1％     6282  1189  AAGAUCUGUUuCACCAUUG    0.7％

1185  1185  AUCUGUUCCACCAUUGAAG  91.1％    6283  1189  AgGAUCUGUUCCACCAUUG    0.2％

6251  1185  AUCUGUUuCACCAUUGAAG  0.7％     6284  1189  AAaAUCUGUUCCACCAUUG    0.1％

6252  1185  AcCUGUUCCACCAUUGAAG  6.9％     6285  1189  AAGAcCUGUUCCACCAUUG    6.9％

6253  1185  AUCUGcUCCACCAUUGAAG  0.2％     6286  1189  AAGAUCUGcUCCACCAUUG    0.2％

6254  1185  AUCUGUUaCACCAUUGAAG  0.1％     6287  1189  AAGAUCUGUUaCACCAUUG    0.1％

6255  1185  AUCUGUUCCACCAUUaAAG  0.1％     6288  1189  AAGAUCUGUUCCACCAUUa    0.1％

6256  1185  AcCUGUUCuACCAUUGAAG  0.1％     6289  1189  AAGAcCUGUUCuACCAUUG    0.1％

6257  1185  AcCUGcUCCACCAUUGAAG  0.3％     6290  1189  AAGAcCUGcUCCACCAUUG    0.3％

1186  1186  UCUGUUCCACCAUUGAAGA  91.1％    1190  1190  UGAAGAUCUGUUCCACCAU    90.7％

6258  1186  UCUGUUuCACCAUUGAAGA  0.7％     6291  1190  UGAAGAUCUGUUuCACCAU    0.7％

6259  1186  cCUGUUCCACCAUUGAAGA  6.9％     6292  1190  UGAgGAUCUGUUCCACCAU    0.2％

6260  1186  UCUGcUCCACCAUUGAAGA  0.2％     6293  1190  cGAAGAUCUGUUCCACCAU    0.1％

6261  1186  UCUGUUaCACCAUUGAAGA  0.1％     6294  1190  UGAAaAUCUGUUCCACCAU    0.1％

6262  1186  UCUGUUCCACCAUUaAAGA  0.1％     6295  1190  UGAAGAcCUGUUCCACCAU    6.8％

6263  1186  cCUGUUCuACCAUUGAAGA  0.1％     6296  1190  UGAAGAUCUGcUCCACCAU    0.2％

6264  1186  cCUGcUCCACCAUUGAAGA  0.3％     6297  1190  UGAAGAUCUGUUaCACCAU    0.1％

1187  1187  GAUCUGUUCCACCAUUGAA  90.9％    6298  1190  UGAAGAcCUGUUCuACCAU    0.1％

6265  1187  GAUGUGUUuCACCAUUGAA  0.7％     6299  1190  UaAAGAcCUGUUCCACCAU    0.1％

6266  1187  aAUCUGUUCCACCAUUGAA  0.1％     6300  1190  UGAAGAcCUGcUCCACCAU    0.2％

6267  1187  GAcCUGUUCCACCAUUGAA  6.9％     1191  1191  AGAUCUGUUCCACCAUUGA    90.7％

6268  1187  GAUCUGcUCCACCAUUGAA  0.2％     6301  1191  AGAUCUGUUuCACCAUUGA    0.7％

6269  1187  GAUCUGUUaCACCAUUGAA  0.1％     6302  1191  gGAUCUGUUCCACCAUUGA    0.2％

6270  1187  GAUCUGUUCCACCAUUaAA  0.1％     6303  1191  AaAUCUGUUCCACCAUUGA    0.1％

6271  1187  GAcCUGUUCuACCAUUGAA  0.1％     6304  1191  AGAcCUGUUCCACCAUUGA    6.9％

6272  1187  GAcCUGcUCCACCAUUGAA  0.3％     6305  1191  AGAUCUGcUCCACCAUUGA    0.2％

6306  1191  AGAUCUGUUaCACCAUUGA  0.1％   6354   1197  AGGCCAUGGUGUCUcGGGC    0.4％

6307  1191  AGAUCUGUUCCACCAUUaA  0.1％   6355   1197  AGGCCAUGGUuUCUAGGGC    0.2％

6308  1191  AGAcCUGUUCuACCAUUGA  0.1％   6356   1197  AGGCCAUGGUaUCUAGGaC    0.1％

6309  1191  AGAcCUGcUCCACCAUGA   0.3％   6357   1197  AGGCCAUGGUuUCcAGGGC    0.1％

1192  1192  UGAUAAACAAUGACCUUGG  90.5％  1198   1198  GGAGGCCAUGGUGUCUAGG    89.0％

6310  1192  UGAUAAACAAUGAuCUUGG  3.4％   6358   1198  GGAGGCCAUGGUGUCUgGG    0.1％

6311  1192  UGAUAAAuAAUGACCUUGG  0.6％   6359   1198  GGAGGCaAUGUGUCUAGG     0.1％

6312  1192  UGgUAAACAAUGACCUUGG  0.3％   6360   1198  GGAGGCCAUGaUGUCUAGG    0.2％

6313  1192  UGAUAAACAAcGACCUUGG  3.9％   6361   1198  GGAGGCCAUGGUaUCUAGG    0.6％

6314  1192  UGAUAAACAAUGACCUaGG  1.2％   6362   1198  GGAGGCCAUGGUGUCUAaG    0.1％

1193  1193  AUGAUAAACAAUGACCUUG  90.5％  6363   1198  GGAGGCCAUGGUGUCUAGa    0.2％

6315  1193  AUGAUAAACAAUGAuCUUG  3.4％   6364   1198  GGAGGCCAUGGUGUCUcGG    0.4％

6316  1193  AUGAUAAAuAAUGACCUUG  0.6％   6365   1198  GGAGGCCAUGGUuUCUAGG    0.2％

6317  1193  AUGgUAAACAAUGACCUUG  0.3％   6366   1198  uGAGGCCAUGGUGUCAGG     0.1％

6318  1193  AUGAUAAACAAcGACCUUG  3.9％   6367   1198  GGAGGCCAUGGUuUCcAGG    0.1％

6319  1193  AUGAUAACAAUGACCUaG   1.2％   6368   1198  uGAaGCCAUGGUGUCUAGG    0.3％

1194  1194  CCAUACAGCCAUGGAACAG  89.2％  1199   1199  UGGAGGCCAUGGUGUCUAG    88.9％

6320  1194  CCAUACAGCCAUGGAACgG  0.1％   6369   1199  UGGAGGCCAUGGUGUCUgG    0.1％

6321  1194  CCAUACAGCCAUGGgACAG  1.3％   6370   1199  gGGAGGCCAUGGUGUCUAG    0.3％

6322  1194  CCAUACAGuCAUGGAACAG  0.2％   6371   1199  UGGAGGCaAUGGUGUCUAG    0.1％

6323  1194  CCAUAuAGCCAUGGAACAG  0.6％   6372   1199  UGGAGGCCAUGaUGUCUAG    0.2％

6324  1194  CCuUACAGCCAUGGAACAG  0.2％   6373   1199  UGGAGGCCAUGGUaUCUAG    0.6％

6325  1194  CCcUACAGCCAUGGgACAG  0.1％   6374   1199  UGGAGGCCAUGGUGUCUAa    0.1％

6326  1194  CCuUACAGCCAUGGgACAG  8.1％   6375   1199  UGGAGGCCAUGGUGUCUcG    0.4％

6327  1194  CCuUACAGuCAUGGAACAG  0.1％   6376   1199  UGGAGGCCAUGGUuUCUAG    0.2％

1195  1195  CAUACAGCCAUGGAACAGG  89.2％  6377   1199  UuGAGGCCAUGGUGUCUAG    0.1％

6328  1195  CAUACAGCCAUGGAACgGG  0.1％   6378   1199  UGGAGGCCAUGGUuUCcAG    0.1％

6329  1195  CAUACAGCCAUGGgACAGG  1.3％   6379   1199  UuGAaGCCAUGGUGUCUAG    0.3％

6330  1195  CAUACAGuCAUGGAACAGG  0.2％   6380   1199  UGGAGGCuAUGGUaUCaAG    0.1％

6331  1195  CAUAuAGCCAUGGAACAGG  0.6％   6381   1199  UGGAGGCuAUGGUuUCaAG    0.1％

6332  1195  CuUACAGCCAUGGAACAGG  0.2％   6382   1199  UGGAGGCuAUGGUuUCcAG    0.7％

6333  1195  CcUACAGCCAUGGgACAGG  0.1％   1200   1200  GAGAUCAUGAAGAUCUGUU    88.8％

6334  1195  CuUACAGCCAUGGgACAGG  8.1％   6383   1200  GAGAUCAUGAgGAUCUGUU    0.2％

6335  1195  CuUACAGuCAUGGAACAGG  0.1％   6384   1200  GAaAUCAUGAAGAUCUGUU    0.5％

1196  1196  GAGGCCAUGGUGUCUAGGG  89.1％  6385   1200  GAGAcCAUGAAGAUCUGUU    0.1％

6336  1196  GAGGCCAUGGUGUCUgGGG  0.1％   6386   1200  GAGAUCAcGAAGAUCUGUU    0.1％

6337  1196  GAaGCCAUGGUGUCUAGGG  0.3％   6387   1200  GAGAUCAUGAAaAUCUGUU    0.1％

6338  1196  GAGGCaAUGGUGCUAGGG   0.1％   6388   1200  GAGAUCAUGAAGAcCUGUU    6.9％

6339  1196  GAGGCCAUGaUGUCUAGGG  0.2％   6389   1200  GAGAUCAUGAAGAUCUGcU    0.2％

6340  1196  GAGGCCAUGGUaUCUAGGG  0.5％   6390   1200  GAGAUCcUGAAGAUCUGUU    0.1％

6341  1196  GAGGCCAUGGUGUCUAaGG  0.1％   6391   1200  GAGAUCuUGAAGAUCUGUU    2.0％

6342  1196  GAGGCCAUGGUGUCUAGaG  0.2％   6392   1200  GAGAUCAUaAAGAcCUGUU    0.1％

6343  1196  GAGGCCAUGGUGUCUcGGG  0.4％   6393   1200  GAGAUCAUGAAGAcCUGcU    0.2％

6344  1196  GAGGCCAUGGUuUCUAGGG  0.2％   1201   1201  ACCAAGAAAAUGGUCACAC    88.7％

6345  1196  GAGGCCAUGGUaUCUAGGa  0.1％   6394   1201  ACCAAGAAAAUGGUCACgC    0.3％

6346  1196  GAGGCCAUGGUuUCcAGGG  0.1％   6395   1201  ACCAAGAAAAUGGUuACAC    0.1％

1197  1197  AGGCCAUGGUGUCUAGGGC  89.1％  6396   1201  ACCAAGAAgAUGGUCACAC    0.3％

6347  1197  AGGCCAUGGUGUCUgGGGC  0.1％   6397   1201  ACCAAGAgAAUGGUCACAC    0.4％

6348  1197  AaGCCAUGGUGUCUAGGGC  0.3％   6398   1201  ACCAAaAAAAUGGUCACAC    0.7％

6349  1197  AGGCaAUGGUGUCUAGGGC  0.1％   6399   1201  ACCAAGAAAAUGaUCACAC    0.1％

6350  1197  AGGCCAUGaUGUCUAGGGC  0.2％   6400   1201  ACCAAGAAAAUGGUCACcC    0.1％

6351  1197  AGGCCAUGGUaUCUAGGGC  0.5％   6401   1202  ACCAAGAAuAUGGUCACAC    0.1％

6352  1197  AGGCCAUGGUGUCUAaGGC  0.1％   6402   1201  ACCcAGAAAAUGGUCACAC    0.1％

6353  1197  AGGCCAUGGUGUCUAGaGC  0.2％   6403   1201  ACCAAaAAgAUGGUCACAC    0.2％

6404  1201  ACCAAGAgAAUGGUCACuC  0.1％    1205  1205  CAUGAAGAUCUGUUCCACC    88.6％

6405  1201  ACuAAGAAAAUGGUgACAC  1.1％    6455  1205  CAUGAAGAUCUGUUuCACC    0.7％

6406  1201  ACuAAGAAAAUGGUgACgC  0.1％    6456  1205  CAUGAgGAUCUGUUCCACC    0.2％

6407  1201  ACCAAaAAAAUGGUaACAC  0.1％    6457  1205  CAcGAAGAUCUGUUCCACC    0.1％

6408  1201  ACCAAaAAAAUGGUgACAC  0.1％    6458  1205  CAUGAAaAUCUGUUCCACC    0.1％

6409  1201  ACuAAaAAAAUGGUgACAC  0.5％    6459  1205  CAUGAAGAcCUGUUCCACC    6.8％

6410  1201  ACuAAGAAAAUGaUaACAC  0.2％    6460  1205  CAUGAAGAUCUGcUCCACC    0.2％

1202  1202  CCAAGAAAAUGGUCACACA  88.7％   6461  1205  CAUGAAGAUCUGUUaCACC    0.1％

6411  1202  CCAAGAAAAUGGUCACgCA  0.3％    6462  1205  CcUGAAGAUCUGUUCCACC    0.1％

6412  1202  CCAAGAAAAUGGUuACACA  0.1％    6463  1205  CUUGAAGAUCUGUUCCACC    2.0％

6413  1202  CCAAGAAgAUGGUCACACA  0.3％    6464  1205  CAUGAAGAcCUGUUCuACC    0.1％

6414  1202  CCAAGAgAAUGGUCACACA  0.4％    6465  1205  CAUaAAGAcCUGUUCCACC    0.1％

6415  1202  CCAAaAAAAUGGUCACACA  0.7％    6466  1205  CAUCAAGAcCUGcUCCACC    0.2％

6416  1202  CCAAGAAAAUGaUCACACA  0.1％    1206  1206  AUGAAGAUCUGUUCCACCA    88.6％

6417  1202  CCAAGAAAAUGGUCACcCA  0.1％    6467  1206  AUGAAGAUCUGUUuCACCA    0.7％

6418  1202  CCAAGAAuAUGGUCACACA  0.1％    6468  1206  AUGAgGAUCUGUUCCACCA    0.2％

6419  1202  CCcAGAAAAUGGUCACACA  0.1％    6469  1206  AcGAAGAUCUGUUCCACCA    0.1％

6420  1202  CCAAaAAgAUGGUCACACA  0.2％    6470  1206  AUGAAaAUCUGUUCCACCA    0.1％

6421  1202  CCAAGAgAAUGGUCACuCA  0.1％    6471  1206  AUGAAGAcCUGUUCCACCA    6.8％

6422  1202  CuAAGAAAAUGGUgACACA  1.1％    6472  1206  AUGAAGAUCUGcUCCACCA    0.2％

6423  1202  CuAAGAAAAUGGUgACgCA  0.1％    6473  1206  AUGAAGAUCUGUUaCACCA    0.1％

6424  1202  CCAAaAAAAUGGUaACACA  0.1％    6474  1206  cUGAAGAUCUGUUCCACCA    0.1％

6425  1202  CCAAaAAAAUGGUgACACA  0.1％    6475  1206  uUGAAGAUCUGUUCCACCA    2.0％

6426  1202  CuAAaAAAAUGGUgACACA  0.5％    6476  1206  AUGAAGAcCUGUUCuACCA    0.1％

6427  1202  CuAAGAAAAUGaUaACACA  0.2％    6477  1206  AUaAAGAcCUGUUCCACCA    0.1％

1203  1203  UGACCAAGAAAAUGGUCAC  88.7％   6478  1206  AUGAAGAcCUGcUCCACCA    0.2％

6428  1203  UGACCAAGAAAAUGGUuAC  0.1％    1207  1207  CAAGAAAAUGGUCACACAA    88.6％

6429  1203  UGACCAAGAAgAUGGUCAC  0.3％    6479  1207  CAAGAAAAUGGUCACACAg    0.1％

6430  1203  UGACCAAGAgAAUGGUCAC  0.5％    6480  1207  CAAGAAAAUGGUCACgCAA    0.3％

6431  1203  UaACCAAGAAAAUGGUCAC  0.3％    6481  1207  CAAGAAAAUGGUuACACAA    0.1％

6432  1203  UGACCAAaAAAAUGGUCAC  0.7％    6482  1207  CAAGAAgAUGGUCACACAA    0.3％

6433  1203  UGACCAAGAAAAUGaUCAC  0.1％    6483  1207  CAAGAgAAUGGUCACACAA    0.4％

6434  1203  UGACCAAGAAuAUGGUCAC  0.1％    6484  1207  CAAaAAAAUGGUCACACAA    0.7％

6435  1203  UGACCcAGAAAAUGGUCAC  0.1％    6485  1207  CAAGAAAAUGaUCACACAA    0.1％

6436  1203  UuACCAAGAAAAUGGUCAC  0.1％    6486  1207  CAAGAAAAUGGUCACcCAA    0.1％

6437  1203  UGACCAAaAAgAUGGUCAC  0.2％    6487  1207  CAAGAAuAUGGUCACACAA    0.1％

6438  1203  UGACuAAGAAAAUGGUgAC  1.2％    6488  1207  CcAGAAAAUGGUCACACAA    0.1％

6439  1203  UGACCAAaAAAAUGGUaAC  0.1％    6489  1207  CAAaAAgAUGGUCACACAA    0.2％

6440  1203  UGACuAAGAAAAUGaUAAC  0.2％    6490  1207  CAAGAgAAUGGUCACuCAA    0.1％

1204  1204  AUGACCAAGAAAAUGGUCA  88.7％   6491  1207  uAAGAAAAUGGUgACACAA    0.5％

6441  1204  AUGACCAAGAAAAUGGUuA  0.1％    6492  1207  uAAGAAAAUGGUgACACAg    0.5％

6442  1204  AUGACCAAGAAgAUGGUCA  0.3％    6493  1207  uAAGAAAAUGGUgACgCAA    0.1％

6443  1204  AUGACCAAGAgAAUGGUCA  0.5％    6494  1207  CAAaAAAAUGGUgACCACAA   0.1％

6444  1204  AUaACCAAGAAAAUGGUCA  0.3％    6495  1207  CAAaAAAAUGGUaACACAg    0.1％

6445  1204  AUGACCAAaAAAAUGGUCA  0.7％    6496  1207  uAAaAAAAUGGUgACACAA    0.5％

6446  1204  AUGACCAAGAAAAUGaUCA  0.1％    1208  1208  UCAUGAAGAUCUGUUCCAC    88.5％

6447  1204  AUGACCAAGAAuAUGGUCA  0.1％    6497  1208  UCAUGAAGAUCUGUUuCAC    0.7％

644g  1204  AUGACCcAGAAAAUGGUCA  0.1％    6498  1208  UCAUGAgGAUCUGUUCCAC    0.2％

6449  1204  AUuACCAAGAAAAUGGUCA  0.1％    6499  1208  cCAUGAAGAUCUGUUCCAC    0.1％

6450  1204  AUGACCAAaAAgAUGGUCA  0.2％    6500  1208  UCAcGAAGAUCUGUUCCAC    0.1％

6451  1204  AUGACuAAGAAAAUGGUgA  0.3％    6501  1208  UCAUGAAaAUCUGUUCCAC    0.1％

6452  1204  gUGACuAAGAAAAUGGUgA  0.9％    6502  1208  UCAUGAAGAcCUCUUCCAC    6.8％

6453  1204  AUGACCAAaAAAAUGGUaA  0.1％    6503  1208  UCAUGAAGAUCUGcUCCAC    0.2％

6454  1204  AUGACuAAGAAAAUGaUaA  0.2％    6504  1208  UCAUGAAGAUCUGUUaCAC    0.1％

6505  1208  UCcUGAAGAUCUGUUCCAC  0.1％    6554  1213  ACAUGACCAAGAAuAUGGU    0.1％

6506  1208  UCuUGAAGAUCUGUUCCAC  2.0％    6555  1213  ACAUGACCcAGAAAAUGGU    0.1％

6507  1208  UCAUGAAGAcCUGUUCuAC  0.1％    6556  1213  ACAUuACCAAGAAAAUGGU    0.1％

6508  1208  UCAUaAAGAcCUGUUCCAC  0.1％    6557  1213  ACAUGACCAAaAAgAUGGU    0.2％

6509  1208  UCAUGAAGAcCUGcUCCAC  0.2％    6558  1213  AuAUGACCAAaAAAAUGGU    0.1％

1209  1209  AUCAUGAAGAUCUGUUCCA  88.5％   6559  1213  AuAUGACuAAGAAAAUGaU    0.2％

6510  1209  AUCAUGAAGAUCUGUUuCA  0.7％    1214  1214  CAUGAGGGAAUACAAGCAG    88.4％

6511  1209  AUCAUGAgGAUCUGUUCCA  0.2％    6560  1214  CAUGAGGGgAUACAAGCAG    1.5％

6512  1209  AcCAUGAAGAUCUGUUCCA  0.1％    6561  1214  CAcGAGGGAAUACAAGCAG    0.2％

6513  1209  AUCAcGAAGAUCUGUUCCA  0.1％    6562  1214  CAUaAGGGAAUACAAGCAG    0.1％

6514  1209  AUCAUGAAaAUCUGUUCCA  0.1％    6563  1214  CAUGAaGGAAUACAAGCAG    0.3％

6515  1209  AUCAUGAAGAcCUGUUCCA  6.8％    6564  1214  CAUGAGGGAAUACAAuCAG    0.2％

6516  1209  AUCAUGAAGAUCUGcUCCA  0.2％    6565  1214  CAUGAuGGAAUACAAGCAG    0.1％

6517  1209  AUCAUGAAGAUCUGUUaCA  0.1％    6566  1214  CAUGAGGGAAUuCAAGCcG    0.1％

6518  1209  AUCcUGAAGAUCUGUUCCA  0.1％    6567  1214  CAUGAaGGgAUuCAAGCAG    0.2％

6519  1209  AUCuUGAAGAUCUGUUCCA  2.0％    1215  1215  GAUGAUGGGCAUGUUCAAC    88.4％

6520  1209  AUCAUGAAGAcCUGUUCuA  0.1％    6568  1215  GAUGAUGGGCAUGUUCAAu    8.3％

6521  1209  AUCAUaAAGAcCUGUUCCA  0.1％    6569  1215  GAUGAUGGGCAUGUUuAAC    0.7％

6522  1209  AUCAUGAAGAcCUGcUCCA  0.2％    6570  1215  GAUGAUGGGuAUGUUCAAC    0.3％

1210  1210  GAUGGGCAUGUUCAACAUG  88.4％   6571  1215  GAUGAUGGGCAUGUUuAAu    1.9％

6523  1210  GAUGGGCAUGUUCAAuAUG  8.3％    6572  1215  GAUGAUGGGuAUGUUCAAu    0.1％

6524  1210  GAUGGGCAUGUUuAACAUG  0.7％    6573  1215  GAUGAUGGGuAUGUUuAAu    0.1％

6525  1210  GAUGGGuAUGUUCAACAUG  0.3％    6574  1215  GAUGAUGGGaAUGUUCAAC    0.1％

6526  1210  GAUGGGCAUGUUuAAuAUG  1.9％    1216  1216  AACAUGACCAAGAAAAUGG    88.4％

6527  1210  GAUGGGuAUGUUCAAuAUG  0.1％    6575  1216  AACAUGACCAAGAAgAUGG    0.3％

6528  1210  GAUGGGuAUGUUuAAuAUG  0.1％    6576  1216  AACAUGACCAAGAgAAUGG    0.5％

6529  1210  GAUGGGaAUGUUCAACAUG  0.1％    6577  1216  AACAUGACuAAGAAAAUGG    0.1％

1211  1211  UGAUGGGCAUGUUCAACAU  88.4％   6578  1216  AAuAUGACCAAGAAAAUGG    0.4％

6530  1211  UGAUGGGCAUGUUCAAuAU  8.3％    6579  1216  AAuAUGACuAAGAAAAUGG    0.2％

6531  1211  UGAUGGGCAUGUUuAACAU  0.7％    6580  1216  AAugUGACuAAGAAAAUGG    0.9％

6532  1211  UGAUGGGuAUGUUCAACAU  0.3％    6581  1216  AACAUaACCAAGAAAAUGG    0.3％

6533  1211  UGAUGGGCaUGUUuAAuAU  1.9％    6582  1216  AACAUGACCAAaAAAUGG     0.7％

6534  1211  UGAUGGGuAUGUUCAAuAU  0.1％    6583  1216  AACAUGACCAAGAAAAUGa    0.1％

6535  1211  UGAUGGGuAUGUUuAAuAU  0.1％    6584  1216  AACAUGACCAAGAuAUGG     0.1％

6536  1211  UGAUGGGaAUGUUCAACAU  0.1％    6585  1216  AACAUGACCcAGAAAAUGG    0.1％

1212  1212  AUGAGGGAAUACAAGCAGG  88.4％   6586  1216  AACAUuACCAAGAAAAAUGG   0.1％

6537  1212  AUGAGGGgAUACAAGCAGG  1.5％    6587  1216  AACAUGACCAAaAAgAUGG    0.2％

6538  1212  AcGAGGGAAUACAAGCAGG  0.2％    6588  1216  AAuAUGACCAAaAAAAUGG    0.1％

6539  1212  AUaAGGGAAUACAAGCAGG  0.1％    6589  1216  AAuAUGACuAAGAAAAUGa    0.2％

654U  1212  AUGAaGGAAUACAAGCAGG  0.3％    1217  1217  AUGAUGGGCAUGUUCAACA    88.4％

6541  1212  AUGAGGGAAUACAAuCAGG  0.2％    6590  1217  AUGAUGGGCAUGUUCAAuA    8.3％

6542  1212  AUGAuGGAAUACAAGCAGG  0.1％    6591  1217  AUGAUGGGCAUGUUuAACA    0.7％

6543  1212  AUGAGGGAAUuCAAGCcGG  0.1％    6592  1217  AUGAUGGGuAUGUUCAACA    0.3％

6544  1212  AUGAaGGgAUuCAAGCAGG  0.2％    6593  1217  AUGAUGGGCAUGUUuAAuA    1.9％

1213  1213  ACAUGACCAAGAAAAUGGU  88.4％   6594  1217  AUGAUGGGuAUGUUCAAuA    0.1％

6545  1213  ACAUGACCAAGAAgAUGGU  0.3％    6595  1217  AUGAUGGGuAUGUUuAAuA    0.1％

6546  1213  ACAUGACCAAGAgAAUGGU  0.5％    6596  1217  AUGAUGGGaAUGUUCAACA    0.1％

6547  1213  ACAUGACuAAGAAAAUGGU  0.1％    1218  1218  CAUGACCAAGAAAAUGGUC    88.3％

6548  1213  AuAUGACCAAGAAAAUGGU  0.44％   6597  1218  CAUGACCAAGGAAAAUGGUu   0.1％

6549  1213  AuAUGACuAAGAAAAUGGU  0.2％    6598  1218  CAUGACCAAGAAgAUGGUC    0.3％

6550  1213  AugUGACuAAGAAAAUGGU  0.9％    6599  1218  CAUGACCAAGAgAAUGGUC    0.5％

6551  1213  ACAUaACCAAGAAAAUGGU  0.3％    6600  1218  uAUGACCAAGAAAAUGGUC    0.4％

6552  1213  ACAUGACCAAaAAAAUGGU  0.7％    6601  1218  CAUaACCAAGAAAAUGGUC    0.3％

6553  1213  ACAUGACCAAGAAAAUGaU  0.1％    6602  1218  CAUGACCAaAAAAUGGUC     0.6％

6603  1218  CAUGACCAAGAAAAUGaUC    0.1％    6653  1222  AUGGGCAUGUUuAACAUGC    0.7％

6604  1218  CAUGACCAAGAAuAUGGUC    0.1％    6654  1222  AUGGGuAUGUUCAACAUGC    0.3％

6605  1218  CAUGACCcAGAAAAUGGUC    0.1％    6655  1222  AUGGGCAUGUUCAAuAUGu    8.3％

6606  1218  CAUuACCAAGAAAAUGGUC    0.1％    6656  1222  AUGGGCAUGUUuAAuAUGC    1.9％

6607  1218  CAUGACCAAaAAgAUGGUC    0.2％    6657  1222  AUGGGuAUGUUCAAuAUGu    0.1％

6608  1218  CAUGACuAAGAAAAUGGUg    0.1％    6658  1222  AUGGGaAUGUUCAACAUGC    0.1％

6609  1218  uAUGACCAAaAAAAUGGUC    0.1％    1223  1223  ACAACAUGACCAAGAAAAU    88.2％

6610  1218  uAUGACuAAGAAAAUGGUg    0.2％    6659  1223  ACAACAUGACCAAGAAgAU    0.3％

6611  1218  CAUGACCAAaAAAAUGGUa    0.1％    6660  1223  ACAACAUGACCAAGAgAAU    0.5％

1219  1219  CUCAUAGUGAAUGCACCAA    88.3％   6661  1223  ACAACAUGACuAAGAAAAU    0.1％

6612  1219  CUCAUAGUGAAUGCACCAg    0.2％    6662  1223  ACAAuAUGACCAAGAAAAU    0.4％

6613  1219  CUCAUAGUGAAUGCAuCAA    0.4％    6663  1223  AuAACAUGACCAAGAAAAU    0.3％

6614  1219  CUuAUAGUGAAUGCACCAA    0.1％    6664  1223  ACAAuAUGACuAAGAAAAU    0.4％

6615  1219  CUaAUAGUGAAUGCACCAA    0.2％    6665  1223  ACAAugUGACuAAGAAAAU    0.9％

6616  1219  CUCAUAaUGAAUGCACCAA    0.1％    6666  1223  ACAACAUaACCAAGAAAAU    0.3％

6617  1219  CUCAUAGUGAAUGCACaAA    0.1％    6667  1223  ACAACAUCACCAAaAAAAU    0.7％

6618  1219  CUCAUAGUGAAUGCACCuA    0.2％    6668  1223  ACCAACAUGACCAAGAAuAU   0.1％

6619  1219  CUCAUAGUuAAUGCACCAA    0.1％    6669  1223  ACAACAUCACCcAGAAAAU    0.1％

6620  1219  CUCAUuGUGAAUGCACCAA    0.1％    6670  1223  ACAACAUuACCAAGAAAAAU   0.1％

6621  1219  CUCAUcGUaAAUGCACCgA    1.3％    6671  1223  ACAACAUGACCAAaAAgAU    0.2％

6622  1219  CUgAUAGUGAAUGCgCCcA    0.1％    6672  1223  ACAAuAUGACCAAaAAAAU    0.1％

1220  1220  GACCAAGAAAAUGGUCACA    88.3％   1224  1224  AUAGUGAAUGCACCAAAUC    88.2％

6623  1220  GACCAAGAAAAUGGUCACg    0.3％    6673  1224  AUGGUGAAUGCACCAgAUC    0.2％

6624  1220  GACCAAGAAAAUGGUuACA    0.1％    6674  1224  AUAGUGAAUGCAuCAAAUC    0.4％

6625  1220  CACCAAGAAgAUGGUCACA    0.3％    6675  1224  AUAaUGAAUGCACCAAAUC    0.1％

6626  1220  GACCAAGAgAAUGGUCACA    0.4％    6676  1224  AUAGUGAAUGCACaAAAUC    0.1％

6627  1220  aACCAAGAAAAUGGUCACA    0.3％    6677  1224  AUAGUGAAUGCACCAAAcC    0.4％

6628  1220  GACCAAaAAAAUGGUCACA    0.7％    6678  1224  AUAGUGAAUGCACCUAAUC    0.1％

6629  1220  GACCAAGAAAAUGaUCACA    0.1％    6679  1224  AUAGUuAAUGCACCAAAUC    0.1％

6630  1220  GACCAAGAAAAUGGUCACc    0.1％    6680  1224  AUuGUGAAUGCACCAAAUC    0.1％

6631  1220  GACCAAGAAuAUGGUCACA    0.1％    6681  1224  AUAGUGAAUGCACCuAgUC    0.1％

6632  1220  GACCcAGAAAAUGGUCACA    0.1％    6682  1224  AUuGUGAAUGCACCcAAUC    1.1％

6633  1220  uACCAAGAAAAUGGUCACA    0.1％    6683  1224  AUcGUaAAUGCACCgAAUC    1.3％

6634  1220  GACCAAaAAgAUGGUCACA    0.2％    1225  1225  UAGUGAAUGCACCAAAUCA    88.2％

6635  1220  GACCAAGAgAAUGGUCACu    0.1％    6684  1225  UAGUGAAUGCACCAgAUCA    0.2％

6636  1220  GACuAAGAAAAUGGUgACA    1.1％    6685  1225  UAGUGAAUGCAuCAAAUCA    0.4％

6637  1220  GACuAAGAAAAUGGUgACg    0.1％    6686  1225  UAaUGAAUGCACCAAAUCA    0.1％

6638  1220  GACCAAaAAAAUGGUaACA    0.1％    6687  1225  UAGUGAAUGCACaAAAUCA    0.1％

663g  1220  GACuAAGAAAAUGaUaACA    0.2％    6688  1225  UAGUGAAUGCACCAAAcCA    0.4％

1221  1221  UCAUAGUGAAUGCACCAAA    88.3％   6689  1225  UAGUGAAUGCACCuAAUCA    0.1％

6640  1221  UCAUAGUGAAUGCACCAgA    0.2％    6690  1225  UAGUuAAUGCACCAAAUCA    0.1％

6641  1221  UCAUAGUGAAUGCAuCAAA    0.4％    6691  1225  UuGUGAAUGCACCAAAUCA    0.1％

6642  1221  UuAUAGUGAAUGCACCAAA    0.1％    6692  1225  UAGUGAAUGCACCuAgUCA    0.1％

6643  1221  UaAUAGUGAAUGCACCAAA    0.2％    6693  1225  UuGUGAAUGCACCcAAUCA    1.1％

6644  1221  UCAUAaUGAAUGCACCAAA    0.1％    6694  1225  UcGUaAAUGCACCgAAUCA    1.3％

6645  1221  UCAUAGUGAAUGCACaAAA    0.1％    1226  1226  GCCAUGGUGUCUAGGGCCC    88.2％

6646  1221  UCAUAGUGAAUGCACCuAA    0.1％    6695  1226  GCCAUGGUGUCUAGGGGCuC   1.3％

6647  1221  UCAUAGUuAAUGCACCAAA    0.1％    6696  1226  GCCAUGGUGUCUgGGGCCC    0.1％

6648  1221  UCAUuGUGAAUGCACCAAA    0.1％    6697  1226  GCaAUGGUGUCUAGGGCCC    0.1％

6649  1221  UCAUAGUGAAUGCACCuAg    0.1％    6698  1226  GCCAUGaUGUCUAGGGCCC    0.2％

6650  1221  UCAUcGUaAAUGCACCgAA    1.3％    6699  1226  GCCAUGGUaUCUAGGGCCC    0.4％

6651  1221  UgAUAGUGAAUGCgCCcAA    0.1％    6700  1226  GCCAUGGUGUCUAaGGCCC    0.1％

1222  1222  AUGGGCAUGUUCAACAUGC    88.2％   6701  1226  GCCAUGGUGUCUAGaGCCC    0.2％

6652  1222  AUGGGCAUGUUCAACAUGu    0.2％    6702  1226  GCCAUGGUGUCUcGGGcCCC   0.3％

6703  1226  GCCAUGGUuUCUAGGGCCC    0.02％   6753   1230  CAACAUuACCAAGAAAAUG    0.1％

6704  1226  GCCAIGGIGICIcGGGCuC    0.1％    6754   1230  CAACAUGACCAAaAAgAUG    0.2％

6705  1226  GCCAUGGUaUcUAGGaCCC    0.1％    6755   1230  CAAuAUGACCAAaAAAAUG    0.1％

6706  1226  GCCAUGGUaUCUAGGGCCa    0.1％    6756   1230  CAACAUGAgCAAGAAAAaG    0.1％

6707  1226  GCCAUGGUuUCcAGGGCCC    0.1％    1231   1231  UGAAUGCACCAAAUCAUGA    88.1％

1227  1227  GACAACAUGACCAAGAAAA    88.2％   6757   1231  UGAAUGCACCAgAUCAUGA    0.2％

6708  1227  GACAACAUGACCAAGAAgA    0.3％    6758   1231  UGAAUGCAuCAAAUCAUGA    0.4％

6709  1227  GACAACAUGACCAAGAgAA    0.5％    6759   1231  UGAAUGCACaAAAUCAUGA    0.1％

6710  1227  GACAACAUGACuAAGAAAA    0.1％    6760   1231  UGAAUGCACCAAAcCAUGA    0.4％

6711  1227  GACAAuAUGACCAAGAAAA    0.4％    6761   1231  UGAAUGCCCCAAAUCAcGA    0.2％

6712  1227  GAuAACAUGACCAAGAAAA    0.3％    6762   1231  UGAAUGCACCAAAUCAUaA    0.1％

6713  1227  GACAAuAUGACuAAGAAAA    0.4％    6763   1231  UGAAUGCACCcAAUGAUGA    0.5％

6714  1227  GACAAugUGGCuAAGAAAA    0.9％    6764   1231  UGAAUGCACCuAAUCAUGA    0.1％

6715  1227  GACAACAUaACCAAGAAAA    0.3％    6765   1231  UuAAUGCACCAAAUCAUGA    0.1％

6716  1227  GACAACAUGACCAAaAAAA    0.7％    6766   1231  UaAAUGCACCgAAUCAUGA    1.3％

6717  1227  GACAACAUGACCAAGAAuA    0.1％    6767   1231  UGAAUGCACCuAgUCAUGA    0.1％

6718  1227  GACAACAUGACCcAGAAAA    0.1％    6768   1231  UaAAUGCgCCgAAUCAUGA    0.1％

6719  1227  GACAACAUuACCAAGAAAA    0.1％    6769   1231  UaAAUGcACCcAAUCAUGA    0.1％

6720  1227  GACAACAUGACCAAaAAgA    0.2％    6770   1231  UGAAUGCACCcAAUCAUGc    0.5％

6721  1227  GACAAuAUGACCAAaAAAA    0.1％    6771   1231  UaAAcGCACCgAAUCAUGA    0.2％

1228  1228  UGGGCAUGUUCAACAUGGU    88.2％   1232   1232  GUGAAUGCACCAAAUCAUG    88.0％

6722  1228  UGGGCAUGUUCAACAUGuU    0.2％    6772   1232  GUGAAUGCACCAgAUCAUG    0.2％

6723  1228  UGGGCAUGUUuAACAUGCU    0.7％    6773   1232  GUGAAUGCAuCAAAUCAUG    0.4％

6724  1228  UGGGuAUGUUCAACAUGCU    0.3％    6774   1232  aUGAAUGCACCAAAUCAUG    0.1％

6725  1228  UGGGCAUGUUCAAuAUGuU    8.3％    6775   1232  GUGAAUGCACaAAAUCAUG    0.1％

6726  1228  UGGGCAUGUUUAAuAUGCU    1.9％    6776   1232  GUGAAUGCACCAAAcCAUG    0.4％

6727  1228  UGGGuAUGUUCAAuAUGuU    0.1％    6777   1232  GUGAAUGCACCAAAUCAcG    0.2％

6728  1228  UGGGaAUGUUCAACAUGCU    0.1％    6778   1232  GUGAAUGCACCAAAUCAUa    0.1％

1229  1229  CCAUGGUGUCUAGGGCCCG    88.2％   6779   1232  GUGAAUGCACCcAAUCAUG    1.1％

6729  1229  CCAUGGUGUCUAGGGCuCG    1.3％    6780   1232  GUGAAUGCACCuAAUCAUG    0.1％

6730  1229  CCAUGGUGUCUgGGGCCCG    0.1％    6781   1232  GUuAAUGCACCAAAUCAUG    0.1％

6731  1229  CaAUGGUGUCUAGGGCCCG    0.1％    6782   1232  GUaAAUGCACCgAAUCAUG    1.3％

6732  1229  CCAUGaUGUCUAGGGCCCG    0.2％    6783   1232  GUGAAUGCACCuAgUCAUG    0.1％

6733  1229  CCAUGGUaUCUAGGGCCCG    0.4％    6784   1232  GUaAAUGCgCCGAAUCAUG    0.1％

6734  1229  CCAUGGUGUCUAaGGCCCG    0.1％    6785   1232  GUaAAUGCACCcAAUCAUG    0.1％

6735  1229  CCAUGGUGUCUAGaGCCCG    0.2％    6786   1232  GUGAAUGCACCcAAcCAUG    0.5％

6736  1229  CCAUGGUGUCUcGGGCCCG    0.3％    6787   1232  GUaAAcGCACCgAAUCAUG    0.2％

6737  1229  CCAUGGUuUCUAGGGCCCG    0.2％    6788   1232  GUGAAUGCACCcAAcuAUG    6.2％

6738  1229  CCAUGGUGUCUcGGGCuCG    0.1％    1233   1233  AGAUCAUGAAGAUCUGUUC    88.0％

6739  1229  CCAUGGUaUCUAGGaCCCG    0.1％    6789   1233  AGAUCAUGAAGAUCUGUUu    0.7％

6740  1229  CCAUGGUaUCUAGGGCCaG    0.1％    6790   1233  AGAUCAUGAgGAUCUGUUC    0.2％

6741  1229  CCAUGGUuUCcAGGGCCCG    0.1％    6791   1233  AaAUCAUGAAGAUCUGUUC    0.5％

1230  1230  CAACAUGACCAAGAAAAUG    88.2％   6792   1233  AGAcCAUGAAGAUCUGUUC    0.1％

6742  1230  CAACAUGACCAAGAAgAUG    0.3％    6793   1233  AGAUCAcGAAGAUCUGUUC    0.1％

6743  1230  CAACAUGACCAAGAgAAUG    0.5％    6794   1233  AGAUCAUGAAaAUCUGUUC    0.1％

6744  1230  CAACAUGACuAAGAAAAUG    0.1％    6795   1233  AGAUCAUGAAGAcCUGUUc    6.9％

6745  1230  CAAuAUGACCAAGAAAAUG    0.4％    6796   1233  AGAUCAUGAAGAUCUGcUC    0.2％

6746  1230  uAACAUGACCAAGAAAAUG    0.3％    6797   1233  AGAUCAUGAAGAUCUGUUa    0.1％

6747  1230  CAAuAUGACuAAGAAAAUG    0.4％    6798   1233  AGAUCcUGAAGAUCUGUUC    0.1％

6748  1230  CAAugUGACuAAGAAAAUG    0.9％    6799   1233  AGAUCuUGAAGAUCUGUUC    2.0％

6749  1230  CAACAUaACCAAGAAAAUG    0.3％    6800   1233  AGAUCAUaAAGAcCUGUUC    0.1％

6750  1230  CAACAUGACCAAaAAAAUG    0.7％    6801   1233  AGAUCAUGAAGAcCUGcUC    0.2％

6751  1230  CAACAUGACCAAGAAuAUG    0.1％    1234   1234  UCAUGAGGGAAUACAAGCA    88.0％

6752  1230  CAACAUGACCcAGAAAAUG    0.1％    6802   1234  UCAUGAGGGgAUACAAGCA    1.5％

6803  1234  cCAUGAGGGAAUACAAGCA    0.4％    6840  1237  aAUCAUGAAGAUCUGUUCC    0.5％

6804  1234  UCAcGAGGGAAUACAAGCA    0.2％    6841  1237  GAcCAUGAAGAUCUGUUCC    0.1％

6805  1234  UCAUaAGGGAAUACAAGCA    0.1％    6842  1237  GAUCAcGAAGAUCUGUUCC    0.1％

6806  1234  UCAUGAaGGAAUACAAGCA    0.3％    6843  1237  GAUCAUGAAaAUCUGUUCC    0.1％

6807  1234  UCAUGAGGGAAUACAAuCA    0.2％    6844  1237  GAUCAUGAAGAcCUGUUCC    6.8％

6808  1234  UCAUGAuGGAAUACAAGCA    0.1％    6845  1237  GAUCAUGAAGAUCUGcUCC    0.2％

6809  1234  UCAUGAGGGAAUuCAAGCc    0.1％    6846  1237  GAUCAUGAAGAUCUGUUaC    0.1％

6810  1234  UCAUGAaGGgAUuCAAGcA    0.2％    6847  1237  GAUCcUGAAGAUCUGUUCC    0.1％

1235  1235  CAGCGCAAAAUGCCAUAAG    88.0％   6848  1237  GAUCuUGAAGAUCUGUUCC    2.0％

6811  1235  CAGCGCAAAAUGCuAUAAG    0.4％    6849  1237  GAUCAUGAAGAcCUGUUCu    0.1％

6812  1235  CAGCGCAgAAUGCCAUAAG    0.2％    6850  1237  GAUCAUaAAGAcCUGUUCC    0.1％

6813  1235  CAGuGCAAAAUGCCAUAAG    0.6％    6851  1237  GAUCAUGAAGAcCUGcUcc    0.2％

6814  1235  CgGCGCAAAAUGCCAUAAG    0.1％    1238  1238  AGUGAAUGCACCAAAUCAU    88.0％

6815  1235  CAGuGCAAAAUGCuAUAAG    1.6％    6852  1238  AGUGAAUGCACCAgAUCAU    0.2％

6816  1235  CAaCGCAAAAUGCCAUAAG    0.1％    6853  1238  AGUGAAUGCAuCAAAUCAU    0.4％

6817  1235  CAGCaCAAAAUGCcAUAAG    0.1％    6854  1238  AaUGAAUGCACCAAAUCAU    0.1％

6818  1235  CAGCGCAAAAUGCaAUAAG    0.2％    6855  1238  AGUGAAUGCACaAAAUCAU    0.1％

6819  1235  CAGCuCAAAAUGCCAUAAG    0.1％    6856  1238  AGUGAAUGCACCAAAcCAU    0.4％

6820  1235  CAuCGCAAAAUGCCAUAAG    0.1％    6857  1238  AGUGAAUGCACCAAAUCAc    0.22％

6821  1235  CAGCacAAAAUGCuAUAAG    8.1％    6858  1238  AGUGAAUGCACCuAAUCAU    0.1％

6822  1235  CAGCaCAAAAUGuuAUAAG    0.1％    6859  1238  AGUuAAUGCACCAAAUCAU    0.1％

6823  1235  CAGCaCAAAgUGCuAUAAG    0.1％    6860  1238  uGUGAAUGCACCAAAUCAU    0.1％

6824  1235  CAGCacAAAAUGCaAUAAG    0.1％    6861  1238  AGUGAAUGCACCuAgUCAU    0.1％

1236  1236  GAAUUCUUGAGGAUGAACA    88.0％   6862  1238  uGUGAAUGCACCcAAUCAU    1.1％

6825  1236  GAAUUCUUGAGGAUGAgCA    0.1％    6863  1238  cGUaAAUGCACCgAAUCAU    1.3％

6826  1236  GAAUUCUUGAGGAUGgACA    0.1％    1239  1239  GGAAUUCUUGAGGAUGAAC    88.0％

6827  1236  GAAUaCUUGAGGAUGAACA    0.2％    6864  1239  GGAAUUCUUGAGGAUGAgC    0.1％

6828  1236  GAAUcCUUGAGGAUGAACA    0.4％    6865  1239  GGAAUUUCUUGAGGAUgAC    0.1％

6829  1236  GAAUUaUUGAGGAUGAACA    0.1％    6866  1239  GGAAUaCUUGAGGAUGAAC    0.2％

6830  1236  GAAUUCUcGAGGAUGAACA    0.1％    6867  1239  GGAAUcCUUGAGGAUGAAC    0.4％

6831  1236  GAAUUCUUGAaGAUGAACA    2.1％    6868  1239  GGAAUUaUUGAGGAUGAAC    0.1％

6832  1236  GAAUUCUUGAGGAcGAACA    0.1％    6869  1239  GGAAUUCUcGAGGAUGAAC    0.1％

6833  1236  GAAUUCUUGAGGAUcAACA    0.3％    6870  1239  GGAAUUCUUGAaGAUGAAC    2.1％

6834  1236  GAAUaCUUGAGGAUGAgCA    0.5％    6871  1239  GGAAUUCUUGAGGAcGAAC    0.1％

6835  1236  GgAUaCUUGAGGAUGAgCA    4.3％    6872  1239  GGAAUUCUUGAGGAUcAAC    0.3％

6836  1236  GAAUaCUUGAaGAUGAACA    1.0％    6873  1239  GGAAUaCUUGAGGAUGAgC    0.5％

6837  1236  GAgUaCUUGAaGAUGAACA    0.2％    6874  1239  GGgAUaCUUGAGGAUGAgC    4.3％

1237  1237  GAUCAUGAAGAUCUGUUCC    88.00％  6875  1239  GGAAUaCUUGAaGAUGAAC    1.0％

6838  1237  GAUCAUGAAGAUCUGUUuC    0.7％    6876  1239  GGAgUACUUGAaGAUGAAC    0.2％

6839  1237  GAUCAUGAgGAUCUGUUCC    0.2％

表20-3.从表1-3所列甲型流感片段3(PA)序列得到的保守和小变体19-mer序列.保守序列匹配所列病毒序列的至少89％，变体含有从参考序列的3个或更少核苷酸变化.

Seq    Ref

ID     ID          匹配序列       ％总数   6881   2391  UUUAaAGCCUAUGUGGAUG    0.1％

2390  2390  UUAGAGCCUAUGUGGAUGG   98.9％   6882   2391  UUUAGAaCCUAUGUGGAUG    0.6％

6877  3390  UUAaAGCCUAUGUGGAUGG   0.1％    6883   2391  UUUAGAGCCUAUGUaGAUG    0 .2％

6878  2390  UUAGAaCCUAUGUGGAUGG   0.6％    6884   2391  UUUAGAGCCUAUGUGGAUa    0.1％

6879  2390  UUAGAGCCUAUGUaGAUGG   0.2％    2392   2392  AGCAAUUGAGGAGUGCCUG    98.7％

6880  2390  UUAGAGCCUAUGUGGAUaG   0.1％    6885   2392  AGcAgUUGAGGAGUGCCUG    0.1％

2391  2391  UUUAGAGCCUAUGUGGAUG   98.9％   6886   2392  AGCAAUUGAGGAaUGCCUG    1.0％

                                           6887   2392  AGCAAUUGAGGAGUGCCUa    0.2％

2393  2393  UUGAGGAGUGCCUGAUUAA    98.7％    6931  2403  AUGAUCCCUGGGUUcUGCU    0.1％

6888  2393  UUGAGGAGUGCCUGgUUAA    0.1％     2404  2404  AAUGAUCCCUGGGUUUUGC    98.0％

6889  2393  UUGAGGAaUGCCUGAUUAA    1.0％     6932  2404  AAcGAUCCCUGGGUUUUGC    1.8％

6890  2393  UUGAGGAGUGCCUaAUUAA    0.2％     6933  2404  AAUGAUCCCUGGGcUUUGC    0.1％

2394  2394  GCAAUUGAGGAGUGCCUGA    98.6％    6934  2404  AAUGAUCCCUGGGUUcUGC    0.1％

6891  2394  GCAAUUGAgGAGUGCCUGg    0.1％     2405  2405  CCUGAUUAAUGAUCCCUGG    97.9％

6892  2394  GCAgUUGAGGAGUGCCUGA    0.1％     6935  2405  CCUGgUUAAUGAUCCCUGG    0.1％

6893  2394  GCAAUUGAGGAaUGCCUGA    1.0％     6936  2405  CCUaAUUAAUGAUCCCUGG    0.2％

6894  2394  GCAAUUGAGGAGUGCCUaA    0.2％     6937  2405  CCUGAUUAAcGAUCCCUGG    1.8％

2395  2395  AUUGAGGAGUGCCUGAUUA    98.6％    2406  2406  UGCCUGAUUAAUGAUCCCU    97.9％

6895  2395  AUUGAGGAGUGCCUGgUUA    0.1％     6938  2406  UGCCUGgUUAAUGAUCCCU    0.1％

6896  2395  gUUGAGGAGUGCCUGAUUA    0.1％     6939  2406  UGCCUaAUUAAUGAUGCCU    0.2％

6897  2395  AUUGAGGAaUGCCUGAUUA    1.0％     6940  2406  UGCCUGAUUAAcGAUCCCU    1.8％

6898  2395  AUUGAGGAGUGCCUaAUUA    0.2％     2407  2407  AUUAAUGAUCCCUGGGUUU    97.9％

2396  2396  CAAUUGAGGAGUGCCUGAU    98.66％   6941  2407  gUUAAUGAUCCCUGGGUUU    0.1％

6899  2396  CAAUUGAGGAGUGCCUGgU    0.1％     6942  2407  AUUAAcGAUCCCUGGGUUU    1.8％

6900  2396  CAgUUGAGGAGUGCCUGAU    0.1％     6943  2407  AUUAAUGAUCCCUGGGcUU    0.1％

6901  2396  CAAUUGAGGGAaUGCUGAU    1.0％     6944  2407  AUUAAUGAUCCCUGGGUUc    0.1％

6902  2396  CAAUUGAGGAGUGCCUaAU    0.2％     2408  2408  GCCUGAUUAAUGAUCCCUG    97.9％

2397  2397  AAUUGAGGAGUGCCUGAUU    98.6％    6945  2408  GCCUGgUUAAUGAUCCCUG    0.1％

6903  2397  AAUUGAGGAGUGCCUGgUU    0.1％     6946  2408  GCCUaAUUAAUGAUCCCUG    0.2％

6904  2397  AgUUGAGGAGUGCCUGAUU    0.1％     6947  2408  GCCUGAUUAAcGAUCCCUG    1.8％

6905  2397  AAUUGAGGAaUGCCUGAUU    1.0％     2409  2409  CUGAUUAAUGAUCCCUGGG    97.9％

6906  2397  AAUUGAGGAGUGCCUaAUU    0.2％     6948  2409  CUGgUUAAUGAUCCCUGGG    0.1％

2398  2398  UAGAGCCUAUGUGGAUGGA    98.3％    6949  2409  CUaAUUAAUGAUCCCUGGG    0.2％

6907  2398  UAGAGCCUAUGUGGAUGGg    0.6％     6950  2409  CUGAUUAAcGAUCCCUGGG    1.8％

6908  2398  UAaAGCCUAUGUGGAUGGA    0.1％     2410  2410  GAUUAAUGAUCCCUGGGUU    97.8％

6909  2398  UAGAaCCUAUGUGGAUGGA    0.6％     6951  2410  GgUUAAUGAUCCCUGGGUU    0.1％

6910  2398  UAGAGCCUAUGUaGAUGGA    0.2％     6952  2410  aAUUAAUGAUCCCUGGGUU    0.2％

6911  2398  UAGAGCCUAUGUGGAUaGA    0.1％     6953  2410  GAUUAAcGAUCCCUGGGUU    1.8％

2399  2399  AGAGCCUAUGUGGAUGGAU    98.3％    6954  2410  GAUUAAUGAUCCCUGGGcU    0.1％

6912  2399  AGAGCCUAUGUGGAUGGgU    0.6％     2411  2411  UGAUUAAUGAUCCCUGGGU    97.8％

6913  2399  AaAGCCUAUGUGGAUGGAU    0.1％     6955  2411  UGgUUAAUGAUCCCUGGGU    0.1％

6914  2399  AGAaCCUAUGUGGAUGGAU    0.6％     6956  2411  UaAUUAAUGAUCCCUGGGU    0.2％

6915  2399  AGAGCCUAUGUaGAUGGAU    0.2％     6957  2411  UGAUUAAcGAUCCCUGGGU    1.8％

6916  2399  AGAGCCUAUGUGGAUaGAU    0.1％     6958  2411  UGAUUAAUGAUCCCUGGGc    0.1％

2400  2400  GAGCCUAUGUGGAUGGAUU    98.2％    2412  2412  UAUAUGAAGCAAUUGAGGA    97.3％

6917  24O0  GAGCCUAUGUGGAUGGgUU    0.6％     6959  2412  UAUAUGAAGCAgUUGAGGA    0.1％

6918  2400  aAGCCUAUGUGGAUGGAUU    0.1％     6960  2412  UAUAUGgAGCAAUUGAGGA    2.6％

6919  2400  GAaCCUAUGUGGAUGGAUU    0.6％     2413  2413  CUAUAUGAAGCAAUUGAGG    97.2％

6920  2400  GAGCCUAUGUaGAUGGAUU    0.2％     6961  2413  CUAUAUGAAGCAgUUGAGG    0.1％

6921  2400  GAGCCUAUGUGGAUaGAUU    0.1％     6962  2413  CUAUAUGgAGCAAUUGAGG    2.6％

6932  2400  GAGCCUAUGUGGAUGGAUa    0.1％     6963  2413  uUAUAUGAAGCAAUUGAGG    0.1％

2401  2401  UAAUGAUCCCUGGGUUUG     98.0％    2414  2414  CUUGGUUCAACUCCUUCCU    97.1％

6923  24O1  UAAcGAUCCCUGGGUUUUG    1.8％     6964  2414  CUUGGUUCAACUCCUUCuU    0.1％

6924  2401  UAAUGAUCCCUGGGcUUUG    0.1％     6965  2414  CUUGGUUuAACUCCUUCCU    0.2％

6925  2401  UAAUGAUCCCUGGGUUcUG    0.1％     6966  2414  CaUGGUUCAACUCCUUCCU    0.1％

2402  2402  UUAAUGAUCCCUGGGUUUU    98.0％    6967  2414  CcUGGUUCAACUCCUUCCU    0.9％

6926  2402  URAAcGAUCCCUGGGUUUU    1.8％     6968  2G14  CgUGGUUCAACUCCUUCCU    1.6％

6927  2402  UUAAUGAUCCCUGGGcUUU    0.1％     2415  2415  UCUUGGUUCAACUCCUUCC    97.1％

6928  2402  UUAAUGAUCCCUGGGUUcU    0.1％     6969  2415  UCUUGGUUCAACUCCUUCu    0.1％

2403  2403  AUGAUCCCUGGGUUUUGCU    98.0％    6970  2415  UCUUGGUUuAACUCCUUCC    0.2％

6929  2403  AcGAUCCCUGGGUUUUGCU    1.8％     6971  2415  UCaUGGUUCAACUCCUUCC    0.1％

6930  2403  AUGAUCCCUGGGcUUUGCU    0.1％     6972  2415  UCcUGGUUCAACUCCUUCC    0.9％

6973  2415 UCgUGGUUCAACUCCUUCC    1.6％    7015  2427 gAGCAAUUGAGGAGUGCCU    2.6％

2416  2416 AGGAGUGCCUGAUUAAUGA    96.9％   7016  2427 AAGCAAUUGAGGAaUGCCU    1.0％

6974  2416 AGGAGUGCCUGgUUAAUGA    0.1％    2428  2428 GAAGCAAUUGAGGAGUGCC    96.4％

6g75  2416 AGGAaUGCCUGAUUAAUGA    1.0％    7O17  2428 GAAGCAgUUGAGGAGUGCC    0.1％

6976  2416 AGGAGUGCCUaAUUAAUGA    0.2％    7018  2428 GgAGCAAUUGAGGAGUGCC    2.6％

6977  2416 AGGAGUGCCUGAUUAAcGA    1.8％    7019  2428 GAAGCAAUUGACCAaUGCC    1.0％

2417  2417 GAGUGCCUGAUUAAUGAUC    96.9％   2429  2429 ACAAAUUUGCAGCAAUAUG    95.4％

6978  2417 GAGUGCCUGgUUAAUGAUC    0.1％    7020  2429 ACAAAUUUGCgGCAAUAUG    0.3％

6979  2417 GAaUGCCUGAUUAAUGAUC    1.0％    7021  2429 ACAAAUUcGCAGCAAUAUG    0.1％

6980  2417 GAGUGCCUaAUUAAUGAUC    0.2％    7022  2429 ACAAAUUUGCuGCAAUAUG    0.4％

6981  2A17 GAGUGCCUGAUUAAcGAUC    1.8％    7023  2429 ACAAgUUUGCuGCAAUAUG    1.5％

2418  2418 UGAGGAGUGCCUGAUUAAU    96.9％   7024  2429 ACAAgUUcGCuGCAAUAUG    1.8％

6982  2418 UGAGGAGUGCCUGgUUAAU    0.1％    2430  2430 AACAAAUUUGCAGCAAUAU    95.4％

6983  2418 UGAGGAaUGCCUGAUUAAU    1.0％    7025  2430 AACAAAUUUGCgGCAAUAU    0.3％

6984  2418 UGAGGAGUGCCUaAUUAAU    0.2％    7026  2430 AACAAAUUcGCAGCAAUAU    0.1％

6985  2418 UGAGGAGUGCCUGAUUAAc    1.8％    7027  2430 AACAAAUUUGCuGCAAUAU    0.4％

2419  2419 GUGCCUGAUUAAUGAUCCC    96.9％   7028  2430 AACAAgUUUGCuGCAAUAU    1.5％

6986  2419 GUGCCUGgUUAAUGAUCCC    0.1％    7029  2430 AACAAgUUcGCuGCAAUAU    1.8％

6987  2419 aUGCCUGAUUAAUGAUCCC    1.0％    2431  2431 GGGCUAUAUGAAGCAAUUG    95.3％

6988  2419 GUGCCUaAUUAAUGAUCCC    0.2％    7030  2431 GGGCUAUAUGAAGCAgUUG    0.1％

6989  2419 GUGCCUGAUUAAcGAUCCC    1.8％    7031  2431 GGGCUAUAUGgAGCAAUUG    2.6％

2420  2420 GGAGUGCCUGAUUAAUGAU    96.9％   7032  2431 GGGuUAUAUGAAGCAAUUG    0.1％

6990  2420 GGAGUGCCUGgUUAAUGAU    0.1％    7033  2431 GGaCUAUAUGAAGCAAUUG    1.9％

6991  2420 GGAaUGCCUGAUUAAUGAU    1.0％    2432  2432 GCUAUAUGAAGCAAUUGAG    95.3％

6992  2420 GGAGUGCCUaAUUAAUGAU    0.2％    7034  2432 GCUAUAUGAAGCAgUUGAG    0.1％

6993  2420 GGAGUGCCUGAUUAAcGAU    1.8％    7035  2432 GCUAUAUGgAGCAAUUGAG    2.6％

2421  2421 GAGGAGUGCCUGAUUAAUG    96.9％   7036  2432 GuUAUAUGAAGCAAUUGAG    0.1％

6994  2421 GAGGAGUGCCUGgUUAAUG    0.1％    7037  2432 aCUAUAUGAAGCAAUUGAG    1.9％

6995  2421 GAGGAaUGCCUGAUUAAUG    1.0％    2433  2433 UCAUGUAUUCAGAUUUUCA    95.3％

6996  2421 GAGGAGUGCCUaAUUAAUG    0.2％    7038  2433 UCAUGUAUUCgGAUUUUCA    1.9％

6997  2421 GAGGAGUGCCUGAUUAAcG    1.8％    7039  2433 UuAUGUAUUCAGAUUUUCA    0.1％

2422  2422 AGUGCCUGAUUAAUGAUCC    96.9％   7040  2433 UCAUGUAcUCAGAUUUUCA    0.1％

6998  2422 AGUGCCUGgUUAAUGAUCC    0.1％    7041  2433 UCAUGUAUUCAGAcUUUCA    0.1％

6999  2422 AaUGCCUGAUUAAUGAUCC    1.0％    7042  2433 UCAUGUAUUCAGAUUUcCA    0.1％

7000  2422 AGUGCCUaAUUAAUGAUCC    0.2％    7043  2433 UCAUGUAUUCgGAUUUcCA    0.1％

7001  2422 AGUGCCUGAUUAAcGAUCC    1.8％    7044  2433 UCAUGUAUUCAGAcUUcCA    2.2％

2423  2423 UAUGAAGCAAUUGAGGAGU    96.4％   2434  2434 GGCUAUAUGAAGCAAUUGA    95.3％

7002  2423 UAUGAAGCAgUUGAGGAGU    0.1％    7045  2434 GGCUAUAUGAAGCAgUUGA    0.1％

7003  2423 UAUGgAGCAAUUGAGGAGU    2.6％    7046  2434 GGCUAUAUGgAGCAAUUGA    2.6％

7004  2423 UAUGAAGCAAUUGAGGAaU    1.0％    7047  2434 GGuUAUAUGAAGCAAUUGA    0.1％

2424  2424 AUAUGAAGCAAUUGAGGAG    96.4％   7048  2434 GaCUAUAUGAAGCAAUUGA    1.9％

7005  2424 AUAUGAAGCAgUUGAGGAG    0.1％    2435  2435 CAAAUUUGCAGCAAUAUGC    95.2％

7006  2424 AUAUGgAGCAAUUGAGGAG    2.6％    7049  2435 CAAAUUUGCAGCAAUAUGu    0.2％

7007  2424 AUAUGAAGCAAUUGAGGAa    1.0％    7050  2435 CAAAUUUGCgGCAAUAUGC    0.3％

2425  2425 AUGAAGCAAUUGAGGAGUG    96.4％   7051  2435 CAAAUUcGCAGCAAUAUGC    0.1％

7008  2425 AUGAAGCAgUUGAGGAGUG    0.1％    7052  2435 CAAAUUUGCuGCAAUAUGC    0.3％

7009  2425 AUGgAGCAAUUGAGGAGUG    2.6％    7053  2435 CAAAUUUGCuGCAAUAUGu    0.1％

7010  2425 AUGAAGCAAUUGAGGAaUG    1.0％    7054  2435 CAAgUUUGGuGCAAUAUGC    1.5％

2426  2426 UGAAGCAAUUGAGGAGUGC    96.4％   7055  2435 CAAgUUcGCuGCAAUAUGC    1.8％

7011  2426 UGAAGCAgUUGAGGAGUGC    0.1％    2436  2436 AAAUUUGCAGCAAUAUGCA    95.2％

7013  2426 UGgAGCAAUUGAGGAGUGC    2.6％    7056  2436 AAAUUUGCAGCAAUAUGuA    0.2％

7013  2426 UGAAGCAAUUGAGGAaUGC    1.0％    7057  2436 AAAUUUGCgGCAAUAUGCA    0.3％

2437  2427 AAGCAAUUGAGGAGUGCCU    96.4％   7058  2436 AAAUUcGCAGCAAUAUGCA    0.1％

7014  2427 AAGCAgUUGAGGAGUGCCU    0.1％    7059  2436 AAAUUUGCuGCAAUAUGCA    0.3％

7060 2436 AAAUUUGCuGCAAUAUGuA    0.1％    7107  2443 AgUUUUAGAGCCUAUGUGG    0.1％

7061 2436 AAgUUUGCuGCAAUAUGCA    1.5％    7108  2443 AAcUUUACAGCCUAUGUGG    4.1％

7062 2436 AAgUUcGCuGCAAUAUGCA    2.1％    7109  2443 AAUUUUAaAGCCUAUGUGG    0.1％

2437 2437 UUCAUGUAUUCAGAUUUUC    95.2％   7110  2443 AAUUUUAGAGCCUAUGUaG    0.2％

7063 2437 UUCAUGUAUUCgGAUUUUC    1.9％    7111  2443 AuUUUUAGAGCCUAUGUGG    0.1％

7064 2437 UUuAUGUAUUCAGAUUUUC    0.1％    7112  2443 AAcUUUAGAaCCUAUGUGG    0.6％

7065 2437 cUCAUGUAUUCAGAUUUUC    0.1％    7113  2443 AccUUUAGAGCCUAUGUGG    0.1％

7066 2437 UUCAUGUAcUCAGAUUUUC    0.1％    2444  2444 AUUUUAGAGCCUAUGUGGA    94.7％

7067 2437 UUCAUGUAUUCAGAcUUUC    0.1％    7114  2444 gUUUUAGAGCCUAUGUGGA    0.1％

7068 2437 UUCAUGUAUUCAGAUUUcC    0.1％    7115  2444 AcUUUAGAGCCUAUGUGGA    4.1％

7069 2437 UUCAUGUAUUCgGAUUUcC    0.1％    7116  2444 AUUUUAaAGCCUAUGUGGA    0.1％

7070 2437 UUCAUGUAUUCAGAcUUcC    2.2％    7117  2444 AUUUUAGAGCCUAUGUaGA    0.2％

2438 2438 AAUUUGCAGCAAUAUGCAC    95.1％   7118  2444 uUUUUAGAGCCUAUGUGGA    0.1％

7071 2438 AAUUUGCAGCAAUAUGCAu    0.1％    7119  2444 AcUUUAGAaCCUAUGUGGA    0.6％

7072 2438 AAUUUGCAGCAAUAUCuAC    0.2％    7120  2444 ccUUUAGAGCCUAUGUGGA    0.1％

7073 2438 AAUUUGCgGCAAUAUGCAC    0.3％    2445  2445 GUAUUCAGAUUUUCAUUUC    94.6％

7074 2438 AAUUcGCAGCAAUAUGCAC    0.1％    7121  2445 GUAUUCgGAUUUUCAUUUC    0.1％

7075 2438 AAUUUGCuGCAAUAUGCAC    0.3％    7122  2445 GUAcUCAGAUUUUCAUUUC    0.1％

7076 2438 AAUUUGCuGCAAUAUGuAC    0.1％    7123  2445 GUAUUCAGAcUUUCAUUUC    0.1％

7077 2438 AgUUUGCuGCAAUAUGCAC    1.5％    7124  2445 GUAUUCAGAUUUUCAcUUC    0.9％

7078 2438 AgUUcGCuGCAAUAUGCAC    2.1％    7125  2445 GUAUUCgGAUUUUCAcUUu    1.8％

2439 2439 ACAAACAAAUUUGCAGCAA    95.0％   7126  2445 GUAUUCAGAcUUcGAUUUC    2.1％

7079 2439 ACAAACAAAUUUGCgGCAA    0.3％    7127  2445 GUAUUCAGAUUUcCAcUUC    0.1％

7080 2439 ACgAACAAAUUUGCAGCAA    0.3％    7128  2445 GUAUUCAGAcUUcCAUUUu    0.1％

7081 2439 ACAAACAAAUUcGCAGCAA    0.1％    7129  2445 GUAUUCgGAUUUcCAcUUC    0.1％

7082 2439 ACAAACAAAUUUGCuGCAA    0.1％    2446  2446 GCAUCCUGUGCAGCAAUGG    94.6％

7083 2439 ACuAACAAAUUUGCAGCAA    0.1％    7130  2446 GCAUCCUGUGCAGCgAUGG    0.2％

7084 2439 ACgAACAAAUUUGCuGCAA    0.3％    7131  2446 GCAUCCUGUGuAGCAAUGG    0.1％

7085 2439 ACgAACAAgUUUGCuGCAA    1.5％    7132  2446 GCAUCuUGUGCAGCAAUGG    1.1％

7086 2439 ACAAACAAgUUcGCuGCAA    1.8％    7133  2446 GCgUCCUGUGCAGCAAUGG    0.2％

2440 2440 CAAACAAAUUUGCAGCAAU    95.0％   7134  2446 GCAUCCUGUGCAGCcAUGG    1.7％

7087 2440 CAAACAAAUUUGCgGCAAU    0.3％    7135  2446 GCAUCuUGUGCAGCcAUGG    2.0％

7088 2440 CgAACAAAUUUGCAGCAAU    0.3％    7136  2446 GCAUCuUGUGCAGuuAUGG    0.1％

7089 2440 CAAACAAAUUcGCAGCAAU    0.1％    2447  2447 AUGCAUCCUGUGCAGCAAU    94.6％

7090 2440 CAAACAAAUUUGCuGCAAU    0.1％    7137  2447 AUGCAUCCUGUGCAGCgAU    0.2％

7091 2440 CuAACAAAUUUGCAGCAAU    0.1％    7138  2447 AUGCAUCCUGUGuAGCAAU    0.1％

7092 2440 CgAACAAAUUUGCuGCAAU    0.3％    7139  2447 AUGCAUCuUGUGCAGCAAU    1.1％

7093 2440 CgAACAAgUUUGCuGCAAU    1.5％    7140  2447 AUGCgUCCUGUGCAGCAAU    0.2％

7094 2440 CAAACAAgUUcGCuGCAAU    1.8％    7141  2447 AUGCAUCCUGUGCAGCcAU    1.7％

2441 2441 AAACAAAUUUGCAGCAAUA    95.0％   7142  2447 AUGCAUCuUGUGCAGCcAU    2.0％

7095 2441 AAACAAAUUUGCgGCAAUA    0.3％    7143  2447 AUGCAUCuUGUGCAGuuAU    0.1％

7096 244U gAACAAAUUUGCAGCAAUA    0.3％    2448  2448 UAUUCAGAUUUUCAUUUCA    94.6％

7097 2441 AAACAAAUUcGCAGCAAUA    0.1％    7144  2448 UAUUCgGAUUUUCAUUUCA    0.1％

7098 2441 AAACAAAUUUCGuGCAAUA    0.1％    7145  2448 UAcUCAGAUUUUCAUUUCA    0.1％

7099 2441 uAACAAAUUUGCAGCAAUA    0.1％    7146  2448 UAUUCAGAcUUUCAUUUCA    0.1％

7100 2441 gAACAAAUUUGCuGCAAUA    0.3％    7147  2448 UAUUCAGAUUUUCAcUUCA    0.9％

7101 2441 gAACAAgUUUGCuGCAAUA    1.5％    7148  2448 UAUUCgGAUUUUCAcUUuA    1.5％

7102 2441 AAACAAgUUcGCuGCAAUA    1.8％    7149  2448 UAUUCAGAcUUcCAUUUCA    2.1％

2443 2442 UUUUAGAGCCUAUGUGGAU    94.9％   7150  2448 UAUUCAGAUUUcCAcUUCA    0.1％

7103 2442 cUUUAGAGCCUAUGUGGAU    4.2％    7151  2448 UAUUCAGAcUUcCAUUUuA    0.1％

7104 2442 UUUUAaAGCCUAUGUGGAU    0.1％    7152  2448 UAUUCgGAUUUcCAcUUCA    0.1％

7105 2442 UUUUAGAGCCUAUGUaGAU    0.2％    2449  2449 GAAACAAACAAAUUUGCAG    94.6％

7106 2442 cUUUAGAaCCUAUGUGGAU    0.6％    7153  2449 GAAACAAACAAAUUUGCgG    0.3％

2443 2443 AAUUUUAGAGCCUAUGUGG    94.7％   7154  2449 GAAACgAACAAAUUUGCAG    0.3％

7155  2449 GAgACAAACAAAUUUGCAG  0.4％    7203   2455 AcUCAGAUUUUCAUUUCAU    0.1％

7156  2449 GAAACAAACAAAUUcGCAG  0.1％    7204   2455 AUUCAGAcUUUCAUUUCAU    0.1％

7157  2449 GAAACAAACAAAUUUGCuG  0.1％    7205   2455 AUUCAGAUUUUCAcUUCAU    0.9％

7158  2449 GAAACuAACAAAUUUGCAG  0.1％    7206   2455 AUUCgCAUUUUCAcUUuAU    1.5％

7159  2449 GAAACgAACAAAUUUGCuG  0.3％    7207   2455 AUUCAGAcUUcCAUUUCAU    2.1％

7160  2449 GAAACgAACAAgUUUGCuG  1.5％    7208   2455 AUUCAGAUUUcCAcUUCAU    0.1％

7161  2449 GAAACAAACAAgUUcGCuG  1.8％    7209   2455 AUUCAGAcUUcCAUUUuAU    0.1％

2450  2450 UGUAUUCAGAUUUUCAUUU  94.6％   7210   2455 AUUCgGAUUUcCAcUUCAU    0.1％

7162  2450 UGUAUUCgGAUUUUCAUUU  0.1％    2456   2456 AUGUAUUCAGAUUUUCAUU    94.6％

7163  2450 UGUAcUCAGAUUUUCAUUU  0.1％    7211   2456 AUGUAUUCgCAUUUUCAUU    0.1％

7164  2450 UGUAUUCAGAcUUUCAUUU  0.1％    7212   2456 AUGUAcUCAGAUUUUCAUU    0.1％

7165  2450 UGUAUUCAGAUUUUCAcUU  0.9％    7213   2456 AUGUAUUCAGAcUUUCAUU    0.1％

7166  2450 UGUAUUCgGAUUUUCAcUU  1.8％    7214   2456 AUGUAUUCAGAUUUUCAcU    0.9％

7167  2450 UGUAUUCAGAcUUcCAUUU  2.2％    7215   2456 AUGUAUUCgGAUUUUCAcU    1.8％

7168  2450 UGUAUUCAGAUUUcCAcUU  0.1％    7216   2456 AUGUAUUCAGAcUUcCAUU    2.2％

7169  2450 UGUAUUCgGAUUUcCAcUU  0.1％    7217   2456 AUGUAUUCAGAUUUcCAcU    0.1％

2451  2451 AAUGCAUCCUGUGCAGCAA  94.6％   7218   2456 AUGUAUUCgGAUUUcCAcU    0.1％

7170  2451 AAUGCAUCCUGUGCAGCgA  0.2％    2457   2457 UGCAUCCUGUGCAGCAAUG    94.6％

7171  2451 AAUGCAUCCUGUGuAGCAA  0.1％    7219   2457 UGCAUCCUGUGCAGCgAUG    0.2％

7173  2451 AAUGCAUCuUGUGCAGCAA  1.1％    7220   2457 UGCAUCCUGUGuAGCAAUG    0.1％

7173  2451 AAUGCgUCCUGUGCAGCAA  0.2％    7221   2457 UGCAUCuUGUGCAGCAAUG    1.1％

7174  2451 AAUGCAUCCUGUGCAGCcA  1.7％    7222   2457 UGCgUCCUGUGCAGCAAUG    0.2％

7175  2451 AAUGCAUCuUGUGCAGCcA  2.0％    7223   2457 UGCAUCCUGUGCAGCcAUG    1.7％

7176  2451 AAUGCAUCuUGUGCAGuuA  0.1％    7224   2457 UGCAUCuUGUGCAGCcAUG    2.0％

2452  2452 AACAAACAAAUUUGCAGCA  94.6％   7225   2457 UGCAUCuUGUGCAGuuAUG    0.1％

7177  2452 AACAAACAAAUUUGCgGCA  0.3％    2458   2458 CAUGUAUUCAGAUUUUCAU    94.5％

7178  2452 AACgAACAAAUUUGCAGCA  0.3％    7226   2458 CAUGUAUUCgGAUUUUCAU    0.1％

7179  2452 gACAAACAAAUUUGCAGCA  0.4％    7227   2458 uAUGUAUUCAGAUUUUCAU    0.1％

7180  2452 AACAAACAAAUUcGCAGCA  0.1％    7228   2458 CAUGUAcUCAGAUUUUCAU    0.1％

7181  2452 AACAAACAAAUUUGCuGCA  0.1％    7229   2458 CAUGUAUUCAGAcUUUCAU    0.1％

7182  2452 AACuAACAAAUUUGCAGCA  0.1％    7230   2458 CAUGUAUUCAGAUUUUCAc    0.9％

7183  2452 AACgAACAAAUUUGCuGCA  0.3％    7231   2458 CAUGUAUUCgGAUUUUCAc    1.8％

7184  2452 AACgAACAAgUUUGCuGCA  1.5％    7232   2458 CAUGUAUUCAGAcUUcCAU    2.2％

7185  2452 AACAAACAAgUUcGCuGCA  1.8％    7233   2458 CAUGUAUUCAGAUUUcCAc    0.1％

2453  2453 AAACAAACAAAUUUGCAGC  94.6％   7234   2458 CAUGUAUUCgGAUUUcCAc    0.1％

7186  2453 AAACAAACAAAUUUGCgGC  0.3％    2459   2459 AGAAUUUUAGAGCCUAUGU    94.3％

7187  2453 AAACgAACAAAUUUGCAGC  0.3％    7235   2459 AGAgUUUUAGAGCCUAUGU    0.1％

7188  2453 AgACAAACAAAUUUGCAGC  0.4％    7236   2459 AaAAUUUUAGAGCCUAUGU    0.5％

7189  2453 AAACAAACAAAUUcGCAGC  0.1％    7237   2459 AGAAcUUUAGAGCCUAUGU    0.5％

7190  2453 AAACAAACAAAUUUGCuGC  0.1％    7238   2459 AGAAUUUUAaAGCCUAUGU    0.1％

7191  2453 AAACuAACAAAUUUGCAGC  0.1％    7239   2459 AGAuUUUUAGAGCCUAUGU    0.1％

7192  2453 AAACgAACAAAUUUGCuGC  0.3％    7240   2459 AaAAcUUUAGAGCCUAUGU    3.5％

7193  2453 AAACgAACAAgUUUGCuGC  1.5％    2460   2460 GAGAAUUUUAGAGCCUAUG    94.2％

7194  2453 AAACAAACAAgUUcGCuGC  1.8％    7241   2460 GAGAgUUUUAGAGCCUAUG    0.1％

2454  2454 CAUCCUGUGCAGCAAUGGA  94.6％   7242   2460 aAGAAUUUUAGAGCCUAUG    0.1％

7195  2454 CAUCCUGUGCAGCgAUGGA  0.2％    7243   2460 GAaAAUUUUAGAGCCUAUG    0.5％

7196  2454 CAUCCUGUGuAGCAAUGGA  0.1％    7244   2460 GAGAAcUUUAGAGCCUAUG    0.5％

7197  2454 CAUCuUGUGCAGCAAUGGA  1.1％    7245   2460 GAGAAUUUUAaAGCCUAUG    0.1％

7198  2454 CgUCCAGUGCAGCAAUGGA  0.2％    7246   2460 GAGAuUUUUAGAGCCUAUG    0.1％

7199  2454 CAUCCUGUGCAGCcAUGGA  1.7％    7247   2460 GAaAAcUUUAGAGCCUAUG    3.5％

7200  2454 CAUCuUGUGCAGCcAUGGA  2.0％    2461   2461 GAUUUUCAUUUCAUCAAUG    94.2％

7201  2454 CAUCuUGUGCAGuuAUGGA  0.1％    7248   2461 GAUUUUCAUUUCAUuAAUG    0.5％

2455  2455 AUUCAGAUUUUCAUUUCAU  94.6％   7249   2461 GAcUUUCAUUUCAUCAAUG    0.1％

7202  2455 AUUCgCAUUUUCAUUUCAU  0.1％    7250   2461 GAUUUUCAcUUCAUCAAUG    0.7％

7251  2461 GAUUUUCAcUUCAUcgAUG    0.1％    7298  2468 GUUCAGGCUCUcAGGGACA    0.3％

7252  2461 CAUUUcCAcUUCAUCAAUG    0.2％    7299  2468 GUUCAGGCUCUUAaGGACA    0.2％

2462  2462 UGAGAAUUUUAGAGCCUAU    94.2％   7300  2468 GUUCAGGCUCUUAGaGACA    0.2％

7253  2462 UGAGAgUUUUAGAGCCUAU    0.1％    7301  2468 GUUCAGGCUCUUcGGGACA    0.3％

7254  2462 UaAGAAUUUUAGAGCCUAU    0.1％    7302  2468 GcUCAGGCaCUUAGGGACA    1.8％

7255  2462 UGAaAAUUUUAGAGCCUAU    0.5％    7303  2468 GUUCAaGCaCUUAGGGACA    2.3％

7256  2462 UGAGAAcUUUAGAGCCUAU    0.5％    7304  2468 GUUCAGGCUCUUAAGGAaA    0.1％

7257  2462 UGAGAAUUUUAaAGCCUAU    0.1％    2469  2469 UUCAGGCUCUUAGGGACAA    94.1％

7258  2462 UGAGAuUUUUAGAGCCUAU    0.1％    7305  2469 UUCAGGCUCUUAGGGACAg    0.1％

7259  2462 UGAaAAcUUUAGAGCCUAU    3.5％    7306  2469 UUCAGGCUCUUAGGGAuAA    0.1％

2463  2463 UUGAGAAUUUUAGAGCCUA    94.2％   7307  2469 UUCAGGCUuUUAGGGACAA    0.1％

7260  2463 UUGAGAgUUUUAGAGCCUA    0.1％    7308  2469 UcCAGGCUCUUAGGGACAA    0.1％

7261  2463 UUaAGAAUUUUAGAGCCUA    0.1％    7309  2469 UUCAGGCcCUUAGGGACAA    0.1％

7262  2463 UUGAaAAUUUUAGAGCCUA    0.5％    7310  2469 UUCAGGCUCUcAGGGACAA    0.3％

7263  2463 UUGAGAAcUUUAGAGCCUA    0.5％    7311  2469 UUCAGGCUCUUAaGGACAA    0.2％

7264  2463 UUGAGAAUUUUAaAGCCUA    0.1％    7312  2469 UUCAGGCUCUUAGaGACAA    0.2％

7265  2463 UUGAGAuUUUUAGAGCCUA    0.1％    7313  2469 UUCAGGCUCUUcGGGACAA    0.3％

7266  2463 UUGAaAAcUUUAGAGCCUA    3.5％    7314  2469 cUCAGGCaCUUAGGGACAA    1.8％

2464  2464 AUUUUCAUUUCAUCAAUGA    94.2％   7315  2469 UUCAaGCaCUUAGGGACAA    2.3％

7267  2464 AUUUUCAUUUCAUuAAUGA    0.5％    7316  2469 UUCAGGCUCUUAaGGAaAA    0.1％

7268  2464 AcUUUCAUUUCAUCAAUGA    0.1％    2470  2470 AGAUUUUCAUUUCAUCAAU    94.1％

7269  2464 AUUUUCAcUUCAUCAAUGA    0.7％    7317  2470 AGAUUUUCAUUUCAUuAAU    0.5％

7270  2464 AUUUUCAcUUCAUCgAUGA    0.1％    7318  2470 gGAUUUUCAUUUCAUCAAU    0.1％

7271  2464 AUUUcCAcUUCAUCAAUGA    0.2％    7319  2470 ACAcUUUCAUUUCAUCAAU    0.1％

2465  2465 UCAGAUUUUCAUUUCAUCA    94.1％   7320  2470 AGAUUUUCAcUUCAUCAAU    0.7％

7272  2465 UCAGAUUUUCAUUUCAUuA    0.5％    7321  2470 AGAUUUUCAcUUCAUCgAU    0.1％

7273  2465 UCgGAUUUUCAUUUCAUCA    0.1％    7322  2470 AGAUUUcCAcUUCAUCAAU    0.1％

7274  2465 UCAGAcUUUCAUUUCAUCA    0.1％    7323  2470 gGAUUUcCAcUUCAUCAAU    0.1％

7275  2465 UCAGAUUUUCAcUUCAUCA    0.7％    2471  2471 UUCAGAUUUUCAUUUCAUC    94.0％

7276  2465 UCAGAUUUUCAcUUCAUCg    0.1％    7324  2471 UUCAGAUUUUCAUUUCAUu    0.5％

7277  2465 UCAGAUUUcCAcUUCAUCA    0.1％    7325  2471 UUCgGAUUUUCAUUUCAUC    0.1％

7278  2466 UCgGAUUUcCAcUUCAUCA    0.1％    7326  2471 cUCAGAUUUUCAUUUCAUC    0.1％

2466  2466 GAAUUUUAGAGCCUAUGUG    94.1％   7327  2471 UUCAGAcUUUCAUUUCAUC    0.1％

7279  2466 GAgUUUUAGAGCCUAUGUG    0.1％    7328  2471 UUCAGAUUUUCAcUUCAUC    0.9％

7280  2466 aAAUUUUAGAGCCUAUGUG    0.5％    7329  2471 UUCAGAUUUcCAcUUCAUC    0.1％

7281  2466 GAAcUUUAGAGCCUAUGUG    0.5％    7330  2471 UUCAGAcUUcCAUUUCAUu    2.1％

7282  2466 GAAUUUUAaAGCCUAUGUG    0.1％    7331  2471 UUCgGAUUUcCAcUUCAUC    0.1％

7283  2466 GAAUUUUAGAGCCUAUGUa    0.2％    2472  2472 AGAGGCGAAGAAACAAUUG    93.7％

7284  2466 GAuUUUUAGAGCCUAUGUG    0.1％    7332  2472 AGAGGCGAAGAgACAAUUG    5.3％

7285  2466 aAAcUUUAGAGCCUAUGUG    3.5％    7333  2472 AGAGGCGAgGAAACAAUUG    0.2％

2467  2467 CAGAUUUUCAUUUCAUCAA    94.1％   7334  2472 AGAGGCGAAaAAACAAUUG    0.1％

7286  2467 CAGAUUUUCAUUUCAUuAA    0.5％    7335  2472 AGAGGCGAAGAAACAAUcG    0.2％

7287  2467 CgGAUUUUCAUUUCAUCAA    0.1％    7336  2472 AGAGGCGAAGAAACnAUUG    0.1％

7288  2467 CAGAcUUUCAUUUCAUCAA    0.1％    7337  2472 AGAGGaGAAGAgACAAUUG    0.3％

7289  2467 CAGAUUUUCAcUUCAUCAA    0.7％    2473  2473 GAGGCGAAGAAACAAUUGA    93.7％

7290  2467 CAGAUUUUCAcUUCAUCgA    0.1％    7338  2473 GAGGCGAAGAgACAAUUGA    5.3％

7291  2467 CAGAUUUcCAcUUCAUCAA    0.1％    7339  2473 GAGGCGAgGAAACAAUUGA    0.2％

7293  2467 CgGAUUUcCAcUUCAUCAA    0.1％    7340  2473 GAGGCGAAaAAACAAUUGA    0.1％

2468  2468 GUUCAGGCUCUUAGGGACA    94.1％   7341  2473 GAGGCGAAGAAACAAUcGA    0.2％

7293  2468 GUUCAGGCUCUUAGGGAuA    0.1％    7342  2473 GAGGCGAAGAAACnAUUGA    0.1％

7294  2468 GUUCAGGCUuUUAGGGACA    0.1％    7343  2473 GAGGaGAAGAgACAAUUGA    0.3％

7295  2468 aUUCAGGCUCUUAGGGACA    0.1％    2474  2474 GGCGAAGAAACAAUUGAAG    93.5％

7296  2468 GUcCAGGCUCUUAGGGACA    0.1％    7344  2474 GGCGAAGAAACAAUUGAgG    0.2％

7297  2468 GUUCAGGCcCUUAGGGACA    0.1％    7345  2474 GGCGAAGAgACVAAUUGAAG   5.3％

7346  2474 GGCGAgGAAACAAUUGAAG    0.2％    7393  2481 UGAAAUGGGGgAUGGAaAU    2.2％

7347  2474 GGCGAAaAAACAAUUGAAG    0.1％    7394  2481 UGAAAUGGGGgAUGGAuAU    0.2％

7348  2474 GGCGAAGAAACAAUcGAAG    0.2％    7395  2481 UGAAAUGGGGAAUaGAGcU    0.1％

7349  2474 GGCGAAGAAACnAUUGAAG    0.1％    7396  2481 UGAAAUGGGGcAUGGAaAU    1.8％

7350  2474 GGaGAAGAgACAAUUGAAG    0.3％    7397  2481 UGAAgUGGGGuAUGGAaAU    0.1％

2475  2475 CGAAGAAACAAUUGAAGAA    93.5％   24B2  2482 AAUGGGGAAUGGAGAUGAG    93.3％

7351  2475 CGAAGAAACAAUUGAgGAA    0.2％    7398  2482 AAUGGGGgAUGGAGAUGAG    1.2％

7352  2475 CGAAGAgACAAUUGAAGAA    5.3％    7399  2482 AAUGGGGAAUGGAaAUGAG    0.6％

7353  2475 CGAgGAAACAAUUGAAGAA    0.2％    7400  2482 AAUGGGGAAUGGAGcUGAG    0.4％

7354  2475 CGAAaAAACAAUUGAAGAA    0.1％    7401  2482 AAUGGGGgAUGGAaAUGAG    2.2％

7355  2475 CGAAGAAACAAUcGAAGAA    0.2％    7402  2482 AAUGGGGgAUGGAuAUGAG    0.2％

7356  2475 CGAAGAAACnAUUGAAGAA    0.1％    7403  2482 AAUGGGGAAUaGAGcUGAG    0.1％

7357  2475 aGAAGAgACAAUUGAAGAA    0.3％    7404  2482 AAUGGGGcAUGGAaAUGAG    1.8％

2476  2476 GCGAAGAAACAAUUGAAGA    93.5％   7405  2482 AgUGGGGuAUGGAaAUGAG    0.1％

7358  2476 GCGAAGAAACAAUUGAgGA    0.2％    2483  2483 CACAUUUUCUCAUUCACUG    93.3％

7359  2476 GCGAAGAgACAAUUGUAGA    5.3％    7406  2483 CACAUUUUCUCgUUCACUG    0.7％

7360  2476 GCGAgGAAACAAUUGAAGA    0.2％    7407  2483 CACAUUUUuUCAUUCACUG    1.1％

7361  2476 GCGAAaAAACAAUUGAAGA    0.1％    7408  2483 CACAUUUUCUCgUUuACUG    0.1％

7362  2476 GCGAAGAAACAAUcGAAGA    0.2％    7409  2483 CACAUcUUCUCAUUCACUG    2.3％

7363  2476 GCGAAGAAACnAUUGAAGA    0.1％    7410  2483 CACAUUUUCUCAUUCACcG    0.1％

7364  2476 GaGAAGAgACAAUUGAAGA    0.3％    7411  2483 CACAUUUUCUCAUUCACUa    0.1％

2477  2477 AGGCGAAGAAACAAUUGAA    93.5％   7412  2483 CACAUUUUCUCcUUCACUG    0.1％

7365  2477 AGGCGAAGAAACAAUUGAg    0.2％    7413  2483 CACAUcUUuUCAUUCACUG    0.3％

7366  2477 AGGCGAAGAgACAAUUGAA    5.3％    7414  2483 CACAUaUUCUCAUUCACaG    1.7％

7367  2477 AGGCGAgGAAACAAUUGAA    0.2％    7415  2483 CACAUaUUCUCAUUCACgG    0.1％

7368  2477 AGGCGAAaAAACAAUUGAA    0.1％    2484  2484 AAAUGGGGAAUGGAGAUGA    93.3％

7369  2477 AGGCGAAGAAACAAUcGAA    0.2％    7416  2484 AAAUGGGGgAUGGAGAUGA    1.2％

7378  2477 AGGCGAAGAAACnAUUGAA    0.1％    7417  2484 AAAUGGGGAAUGGAaAUGA    0.6％

7371  2477 AGGaGAAGAgACAAUUGAA    0.3％    7418  2484 AAAUGGGGAAUGGAGcUGA    0.4％

2478  2478 GAAGAAACAAUUGAAGAAA    93.5％   7419  2484 AAAUGGGGgAUGGAaAUGA    2.2％

7373  2478 GAAGAAACAAUUGAgGAAA    0.2％    7420  2484 AAAUGGGGgAUGGAuAUGA    0.2％

7373  2478 GAAGAgACAAUUGAAGAAA    5.7％    7421  2484 AAAUGGGGAAUaGAGcUGA    0.1％

7374  2478 GAgGAAACAAUUGAAGAAA    0.2％    7422  2484 AAAUGGGGcAUGGAaAUGA    1.8％

7375  2478 GAAaAACAAUUGAAGaAAA    0.1％    7423  2484 AAgUGGGGuAUGGAaAUGA    0.1％

7376  2478 GAAGAAACAAUcGAAGAAA    0.2％    2485  2485 GAAAUGGGGAAUGGAGAUG    93.3％

7377  2478 GAAGAAACnAUUGAAGAAA    0.1％    7424  2485 GAAAUGGGGgAUGGAGAUG    1.2％

2479  2479 AAAUGAAAUGGGGAAUGGA    93.4％   7425  2485 GAAAUGGGGAAUGGAaAUG    0.6％

7378  2479 AAAUGAAAUGGGGgAUGGA    1.4％    7426  2485 GAAAUGGGGAAUGGAGcUG    0.4％

7379  2479 AgAUGAAAUGGGGAAUGGA    1.0％    7427  2485 GAAAUGGGGgAUGGGaAUG    2.2％

7380  2479 AgAUGAAAUGGGGgAUGGA    2.2％    7428  2485 GAAAUGGGGgAUGGAuAUG    0.2％

7381  2479 AAAUGAAAUGGGGAAUaGA    0.1％    7429  2485 GAAAUGGGGAAUaGAGcUG    0.1％

7382  2479 AAAUGAAAUGGGGcAUGGA    1.8％    7430  2485 GAAAUGGGGcAUGGAaAUG    1.8％

7383  2479 AAAUGAAgUGGGGuAUGGA    0.1％    7431  2485 GAAgUGGGGuAUGGAaAUG    0.1％

2480  2480 AAUAUGAAAUGGGGAAUGG    93.4％   2486  2486 AUGAAAUGGGGAAUGGAGA    93.3％

7384  2480 AAAAUGAAAUGGGGgAUGG    1.4％    7432  2486 AUGAAAUGGGGgAUGGAGA    1.2％

7385  2480 AAgAUGAAAUGGGGAAUGG    1.0％    7433  2486 AUGAAAUGGGGAAUGGAaA    0.6％

7386  2480 AAgAUGAAAUGGGGgAUGG    2.2％    7434  2486 AUGAAUUGGGGAAUGGAGc    0.4％

7387  2480 AAAAUGAAAUGGGGAAUaG    0.1％    7435  2486 AUGAAAUGGGGgAUGAGaA    2.2％

7388  2480 AAAAUGAAAUGGGGcAUGG    1.8％    7436  2486 AUGAAAUGGGGgAUGGAuA    0.2％

7389  2480 AAAAUGAAgUGGGGuAUGG    0.1％    7437  2486 AUGAAAUGGGGAAUaGAGc    0.1％

2481  2481 UGAAAUGGGGAAUGGAGAU    93.3％   7438  2486 AUGAAAUGGGGcAUGGAaA    1.8％

7390  2481 UGAAAUGGGGgAUGGAGAU    1.2％    7439  2486 AUGAAgUGGGGuAUGGAaA    0.1％

7391  2481 UGAAAUGGGGAAUGGAaAU    0.6％    2487  2487 ACAUUUUCUCAUUCACUGG    93.2％

7392  2481 UGAAAUGGGGAAUGGAGcU    0.4％    7440  2487 ACAUUUUCUCgUUCACUGG    0.7％

7441  2487 ACAUUUUuUCAUUCACUGG    1.1％    7489  2493 GUgAACUUUGUGAGuAUGG    2.2％

7442  2487 ACAUUUUCUCgUUuACUGG    0.1％    7490  2493 GUAAACUUUaUCAGCAUGG    0.1％

7443  2487 ACAUcUUCUCAUUCACUGG    2.3％    7491  2493 GUAAAuUUUGUaAGuAUGG    0.2％

7444  2487 ACAUUUUCUCAUUCACcGG    0.1％    2494  2494 CAGUCCGAAAGAGGCGAAG    92.5％

7445  2487 ACAUUUUCUCAUUCACUaG    0.1％    7492  2494 CAGUCCGAAAGAGGCGAgG    0.2％

7446  2487 ACAUUUUCUCAUUCACUGa    0.1％    7493  2494 CAGUCCGAgAGAGGCGAAG    3.7％

7447  2487 ACAUUUUCUCcUUCACUGG    0.1％    7494  2494 CAGUCuGAAAGAGGCGAAG    0.2％

7448  2487 ACAUcUUuUCAUUCACUGG    0.3％    7495  2494 CAaUCCGAAAGAGGCGAAG    1.0％

7449  2487 ACAUaUUCUCAUUCACaGG    1.7％    7496  2494 CAGUCaGAAAGAGGCGAAG    0.1％

7450  2487 ACAUaUUCUCAUUCACgGG    0.1％    7497  2494 CAGUCCGAAAGAGGCGAAa    0.1％

2483  2488 AAAGAGGCGAAGAAACAAU    92.8％   7498  2494 CUGUCCGAAAGAGGCGAAG    0.1％

7451  2488 AAAGAGGCGAAGAgACAAU    1.2％    7499  2494 CAaUCCGAgAGAGGCGAAG    1.7％

7452  2488 AAAGAGGCGAgGAAACAAU    0.2％    7500  2494 CAGUCCGAgAGAGGaGAAG    0.3％

7453  2488 AgAGAGGCGAAGAAACAAU    1.2％    2495  2495 AGUCCGAAAGAGGCGAAGA    92.5％

7454  2488 AgAGAGGCGAAGAgACAAU    4.2％    7501  2495 AGUCCGAAAGAGGCGAgGA    0.2％

7455  2488 AAAGAGGCGAAaAAACAAU    0.1％    7502  2495 AGUCCGAgAGAGGCGAAGA    3.7％

7456  2488 AgAGAGGCGAAGAAACnAU    0.1％    7503  2495 AGUCuGAAAGAGGCGAAGA    0.2％

7457  2488 AgAGAGGaGAAGAgACAAU    0.3％    7504  2495 AaUCCGAAAGAGGCGAAGA    1.0％

2489  2489 GAAAGAGGCGAAGAAACAA    92.8％   7505  2495 AGUCaGAAAGAGCGAAUGA    0.1％

7458  2489 GAAAGAGGCGAAGAgACAA    1.2％    7506  2495 AGUCCGAAaGAGGCGAAaA    0.1％

7459  2489 GAAAGAGGCGAgGAAACAA    0.2％    7507  2495 uGUCCGAAAGAGGCGAAGA    0.1％

7460  2489 GAaAGAGGCGAAGAAACAA    1.2％    7508  2495 AaUCCGAgAGAGGCGAAGA    1.7％

7461  2489 GAgAGAGGCGAAGAgACAA    4.2％    7509  2495 AGUCCGAgAGAGGaGUAGA    0.3％

7462  2489 GAAAGAGGCGAAaAAACAA    0.1％    2496  2496 CGAAAGAGGCGAAGAAACA    92.4％

7463  2489 GAgAGAGGCGAAGAAACnA    0.1％    7510  2496 CGAAAGAGGCGAAGAgACA    1.2％

7464  2489 GAgAGAGGaGAAGAgACAA    0.3％    7511  2496 CGAAAGAGGCGAgGAAACA    0.2％

2490  2490 AAUGAAAUGGGGAAUGGAG    92.8％   7512  2496 CGAgAGAGGCGAAGAAACA    1.2％

7465  2490 AAUGAAAUGGGGgAUGGAG    1.2％    7513  2496 uGAAAGAGGCGAAGAAACA    0.2％

7466  2490 gAUGAAAUGGGGAAUGGAG    1.0％    7514  2496 CGAgAGAGGCGAAGAgACA    4.2％

7467  2490 AAUGAAAUGGGGAAUaGAG    0.1％    7515  2496 aGAAAGAGGCGAAGAAACA    0.1％

7464  2490 AAUGAAAUGGGGAAUGGAa    0.6％    7516  2496 CGAAAGAGGCGAAaAAACA    0.1％

7469  2490 AAUGAAAUGGGGgAUGGAa    0.2％    7517  2496 CGAgAGAGGCGAAGAAACn    0.1％

7470  2490 gAUGAAAUGGGGgAUGGAa    2.0％    7518  2496 CGAgAGAGGaGAAGAgACA    0.3％

7471  2490 gAUGAAAUGGGGgAUGGAu    0.2％    2497  2497 UGGUAAACUUUGUGAGCAU    92.4％

7473  2490 AAUGAAAUGGGGcAUGGAa    1.8％    7519  2497 UGGUAAAuUUUGUGAGCAU    3.0％

7473  2490 AAUGAAgUGGGGuAUGGAa    0.1％    7520  2497 UGGUAAAuUUUGUGAGuAU    1.7％

2491  2491 UAAACUUUGUGAGCAUGGA    92.5％   7521  2497 UGGUgAACUUUGUGAGUAU    2.2％

7474  2491 UAAAuUUUGUGAGCAUGGA    3.2％    7522  2497 UGGUAAACUUUaUGAGCAU    0.1％

7475  2491 UAAAuUUUGUGAGuAUGGA    1.7％    7523  2497 UuGUAAACUUUGUGAGCAU    0.1％

7476  2491 UgAACUUUGUGAGuAUGGA    2.2％    7524  2497 UaGUAAAuUUUGUGAGCAU    0.2％

7477  2491 UAAACUUUaUGAGCAUGGA    0.1％    7525  2497 UGGUAAAuUUUGUaAGuAU    0.2％

7478  2491 UAAAuUUUGUaAGuAUGGA    0.2％    2498  2498 GUGGUAAAGUUUGUGAGCA    92.4％

2492  2492 AAGAGGCGAAGAAACAAUU    92.5％   7526  2498 GUGGUAAAuUUUGUGAGCA    3.0％

7479  2492 AAGAGGCGAAGAgACAAUU    1.2％    7527  2498 GUGGUAAAuUUUGUGAGuA    1.7％

7480  2492 AAGAGGCGAgGAAACAAUU    0.2％    7528  2498 GUGGUgAACUUUGUGAGuA    2.2％

7481  2492 gAGAGGCGAAGAAACAAUU    1.2％    7529  2498 GUGGUAAACUUUaUGAGCA    0.1％

7482  2492 gAGAGGCGAAGAgACAAUU    4.2％    7530  2498 GUuGUAAACUUUGUGAGCA    0.1％

7483  2492 AAGAGGCGAAaAAACAAUU    0.1％    7531  2498 GUaGUAAAuUUUGUGAGCA    0.2％

7484  2492 AAGAGGCGAAGAAACAAUc    0.2％    7532  2498 GUGGUAAAuUUUGUaAGuA    0.2％

7485  2492 gAGAGGCGAAGAAACnAUU    0.1％    2499  2499 UUUGUGCGACAAUGCUUCA    92.4％

7486  2492 gAGAGGaGAAGAgACAAUU    0.3％    7533  2499 UUUGUGCGACAAUGCUUuA    0.5％

2493  2493 GUAAACUUUGUGAGCAUGG   92.5％    7534  2499 UUUGUGCGACAAUGuUUCA    2.8％

7487  2493 GUAAAuUUUGUGAGCAUGG    3.2％    7535  2499 UUUGUGCGACAgUGCUUCA    1.2％

7488  2493 GUAAAuUUUGUGAGuAUGG    1.7％    7536  2499 UUUGUGCGgCAAUGCUUCA    0.2％

7537  2499 UgUGUGCGACAAUGCUUCA    0.1％    7586  2504 CGcCAGUCCGAAAGAGGCG    0.2％

7538  2499 UUcGUGCGAGAAUGCUUCA    0.1％    7587  2504 CGUCAaUCCGAAAGAGGCG    1.0％

7539  2499 UUUGUGaGACAAUGCUUCA    0.21％   7588  2504 CGUCAGUCaGAAAGAGGCG    0.1％

7540  2499 UUUGUGCGACAAUGCUUUu    0.1％    7589  2504 CGUCuGUCCGAAAGAGGCG    0.1％

7541  2499 UUUGUGgGACAAUGCUUCA    0.1％    7590  2504 CGUCAaUCCGAgAGAGGCG    1.7％

7542  2499 UUUGUaCGACAAUGCUUuA    1.6％    7591  2504 CGUCAGUCCGAgAGAGGaG    0.3％

2500  2500 UCGUCAGUCCGAAAGAGGC    92.4％   2505  2505 GUCAGUCCGAAAGAGGCGA    92.4％

7543  2500 UCGUCAGUCCGAgAGAGGC    3.7％    7592  2505 GUCAGUCCGAgAGAGGCGA    3.7％

7544  2500 UCGUCAGUCuGAAAGAGGC    0.2％    7593  2505 GUCAGUCUGAAAGAGGCGA    0.2％

7545  2500 UCaUCAGUCCGAAAGAGGC    0.2％    7594  2505 aUCAGUCCGAAAGAGGCGA    0.2％

7546  2500 UCGcCAGUCCCGAAGAGGC    0.2％    7595  2505 GcCAGUCCGAAAGAGGCGA    0.2％

7547  2500 UCGUCAaUCCGAAAGAGGC    1.0％    7596  2505 GUCAaUCCGAAAGAGGCGA    1.0％

7548  2500 UCGUCAGUCaGAAAGAGGC    0.1％    7597  2505 GUCAGUCaGAAAGAGGCGA    0.1％

7549  2500 UCGUCuGUCCGAAAGAGGC    0.1％    7598  2505 GUCUGUCCGAAAGAGGCGA    0.1％

7550  2500 UCGUCAaUCCGAgAGAGGC    1.7％    7599  2505 GUCAaUCCGAgAGAGGCGA    1.7％

7551  2500 UCGUCAGUCCGAgACAGGa    0.3％    7600  2505 GUCAGUCCGAgAGAGGaGA    0.3％

2501  2501 UUGUGCGACAAUGCUUCAA    92.4％   2506  2506 UCAGUCCGAAAGAGGCGAA    92.4％

7552  2501 UUGUGCGACAAUGCUUuAA    0.5％    7601  2506 UCAGUCCGAAAGAGGCGAg    0.2％

7553  2501 UUGUGCGACAAUGuUUCAA    2.8％    7602  2506 UCAGUCCGAgAGAGGCGAA    3.7％

7554  2501 UUGUGCGACAgUGCUUCAA    1.2％    7603  2506 UCAGUCUGAAAGAGGCGAA    0.2％

7555  2501 UUGUGCGgCAAUGCUUCAA    0.2％    7604  2506 cCAGUCCGAAAGAGGCGAA    0.2％

7556  2501 gUGUGCGACAAUGCUUCAA    0.1％    7605  2506 UCAaUCCGAAAGAGGCGAA    1.0％

7557  2501 UcGUGCGACAAUGCUUCAA    0.1％    7606  2506 UCAGUCaGAAAGAGGCGAA    0.1％

7558  2501 UUGUGaGACAAUGCUUCAA    0.2％    7607  2506 UCuGUCCGAAAGAGGCGAA    0.1％

7559  2501 UUGUGCGACAAUGCUUCuA    0.1％    7608  2506 UCAaUCCGAgAGAGGCGAA    1.7％

7560  2501 UUGUGgGACAAUGCUUCAA    0.1％    7609  2506 UCAGUCCGAgAGAGGaGAA    0.3％

7561  2501 UUGUaCGACAAUGCUUuAA    1.6％    2507  2507 GGUAAACUUUGUGAGCAUG    92.4％

2502  2502 UAAGCGAUUUGAAGCAAUA    92.4％   7610  2507 GGUAAAuUUUGUGAGCAUG    3.0％

7562  2502 UAAGCGAUUUGAAGCAgUA    0.4％    7611  2507 GGUAAAuUUUGUGAGuAUG    1.7％

7563  2502 UAAGuGAUUUGAAGCAAUA    0.3％    7612  2507 GGUgAACUUUGUGAGuAUG    2.2％

7564  2502 UAgGCGAUUUGAAGCAAUA    0.3％    7613  2507 GGUAAACUUUaUGAGCAUG    0.1％

7565  2502 UgAGCGAUUUGAAGCAAUA    0.1％    7614  2507 uGUAAACUUUGUGAGCAUG    0.1％

7566  2502 UAgGuGAUUUGAAGCAAUA    0.3％    7615  2507 aGUAAAuUUUGUGAGCAUG    0.2％

7567  2502 cAAGCGAUUUGAAGCAAUA    0.2％    7616  2507 GGUAAAuUUUGUaAGuAUG    0.2％

7568  2502 UAAGCGAcUUGAAGCAAUA    0.2％    2508  2508 UCCGAAAGAGGCGAAGAAA    92.4％

7569  2502 UAAGCGAUcUGAAGCAAUA    0.3％    7617  2508 UCCGAAAGAGGCGAAGAgA    1.2％

7570  2502 UUAGCUGUUUaAAGCUAUA    0.3％    7618  2508 UCCGAAAGAGGCGAgGAAA    0.2％

7571  2502 UAAGCGAUUUGAAaCAAUA    0.2％    7619  2508 UCCGAgAGAGGCgAAGAAA    1.3％

7572  2502 UuAGCGAUUUGAAGCAAUA    0.2％    7620  2508 UCuGAAAGAGGCGAAGAAA    0.2％

7573  2502 UAgGCGAcUUGAAGCAAUA    0.3％    7621  2508 UCCGAgAGAGGCGAAGAgA    4.2％

7574  2502 UcAGCGAUUUaAAGCAAUA    0.1％    7622  2508 UCaGAAAGAGGCGAAGAAA    0.1％

2503  2503 UUCGUCAGUCCGAAAGAGG    92.4％   7623  2508 UCCGAAAGAGGCGAAaAAA    0.1％

7575  2503 UUCGUCAGUCCGAgAGAGG    4.1％    7624  2508 UCCGAgAGAGGaGAAGAgA    0.3％

7576  2503 UUCGUCAGUCUGAAAGAGG    0.2％    2509  2509 CCGAAAGAGGCGAAGAAAC    92.4％

7577  2503 UUCaUCAGUCCGAAAGAGG    0.2％    76Z5  2509 CCGAAUGAGGCGAAGAgAC    1.2％

7578  2503 UUCGcCAGUCCGAAAGAGG    0.2％    7626  2509 CCGAAAGAGGCGAgGAAAC    0.2％

7579  2503 UUCGUCAaUCCGAAAGAGG    1.0％    7627  2509 CCGAgAGAGGCGAAGAAAC    1.3％

7580  2503 UUCGUCAGUCaGAAAGAGG    0.1％    7628  2509 CuGAAAGAGGCGAAGAAAC    0.2％

7581  2503 UUCGUCuGUCCGAAAGAGG    0.1％    7629  2509 CCGAgAGAGGCGAAGAgAC    4.2％

7582  2503 UUCGUCAaUCCGAgAGAGG    1.7％    7630  2509 CaGAAAGAGGCGAAGAAAC    0.1％

2504  2504 CGUCAGUCCGAAAGAGGCG    92.4％   7631  2509 CCGAAAGAGGCGAAaAAAC    0.1％

7583  2504 CGUCAGUCCGAgAGAGGCG    3.7％    7632  2509 CCGAgAGAGGaGAAGAgAC    0.3％

7584  2504 CGUCAGUCuGAAAGAGGCG    0.2％    2510  2510 UUUCGUCAGUCCGAAAGAG    92.4％

7585  2504 CaUCAGUCCGAAAGAGGCG    0.2％    7633  2510 UUUCGUCAGUCCGAgAGAG    4.1％

7634  2510 UUUCGUCAGUCuCAAAGAG    0.2％    7683  2515 AAGCGAUcUGAAGCAAUAU    0.3％

7635  2510 UUUCaUCAGUCCGAAAGAG    0.2％    7684  2515 AAGCGAUUUaAAGCAAUAU    0.3％

7636  2510 UUUCGcCAGUCCGAAAGAG    0.2％    7685  2515 AAGCGAUUGAAaCAAUAAU    0.2％

7637  2510 UUUCGUCAaUCCGAAAGAG    1.0％    7686  2515 AAGCGAUUUGAAGCAAUAc    0.5％

7638  2510 UUUCGUCAGUCaGAAAGAG    0.1％    7687  2515 uAGCGAUUUGAAGCAAUAU    0.2％

7639  2510 UUUCGUCuGUCCGAAAGAG    0.1％    7688  2515 AgGCGAcUUAAGCAAUAAU    0.3％

7640  2510 UUUCGUCAaUCCGAgAGAG    1.7％    7689  2515 cAGCGAUUUaAAGCAAUAU    0.1％

2511  2511 UCCUUUCGUCAGUCCGAAA    92.3％   2516  2516 AAGAUUUGUGCGACAAAUG    92.0％

7641  2511 UCCUUUCGUCAGUCCGAgA    4.1％    7690  2516 AAGAUUUUGUGCGACAgUG    0.9％

7643  2511 UCCUUUCGUCAGUCuGAAA    0.2％    7691  2516 AAGAUUUUGUGCGgCAAUG    0.2％

7643  2511 UCuUUUCGUCAGUCCGAAA    0.1％    7692  2516 AgGAUUUUGUGCGACAAUG    0.2％

7644  2511 UCCUUUCaUCAGUCCGAAA    0.2A％   7693  2516 AAGAaUUUGUGCGACAAUG    0.3％

7645  2511 UCCUUUCGcCAGUCCGAAA    0.2％    7694  2516 AAGAcUUUGUGCGAUAAUG    3.1％

7646  2511 UCCUUUCGUCAaUCCGAAA    1.0％    7695  2516 AAGAUUUcGUGCGACAAUG    0.1％

7647  2511 UCCUUUCGUCAGUCaGAAA    0.1％    7696  2516 AAGAUUUUGUaCGACAAUG    1.6％

7648  2511 UCCUUUCGUCuGUCCGAAA    0.1％    7697  2516 AAGAUUUUGUGaGACAAUG    0.1％

7649  2511 UCCUUUCGUCAaUCCGAgA    1.7％    7698  2516 AAGAUUUUGUGgGACAAUG    0.1％

2512  2512 CCUUUCGUCAGUCCGAAAG    92.3％   7699  2516 AAGAcUUUGUGCGACAgUG    0.3％

7650  2512 CCUUUCGUCAGUCCGAgAG    4.1％    7700  2516 AAGAcUgUGUGCGACAAUG    0.1％

7651  2512 CCUUUCGUCAGUCuGAAAG    0.2％    7701  2516 AAGAUUUUGaGgGACAAUG    0.1％

7652  2512 CUUUUCGUCAGUCCGAAAG    0.1％    2517  2517 AGCGAUUUGAAGCAAUAUG    92.0％

7653  2512 CCUUUCaUCAGUCCCAAAG    0.2％    7702  2517 AGCGAUUUGAAGCAgUAUG    0.4％

7654  2512 CCUUUCGcCAGUCCGAAAG    0.2％    7703  2517 AGuGAUUUGAAGCAAUAUG    0.3％

7655  2512 CCUUUCGUCAaUCCGAAAG    1.0％    7704  2517 gGCGAUUUGAAGCAAUAUG    0.3％

7656  2512 CCUUUCGUCAGUCaGAAAG    0.1％    7705  2517 gGuGAUUUGAAGCAAUAUG    0.3％

7657  2512 CCUUUCGUCuGUCCGAAAG    0.1％    7706  2517 AGCGAcUUGAAGCAAUAUG    0.1％

7658  2512 CCUUUCGUCAaUCCGAgAG    1.7％    7707  2517 AGCGAUcUGAAGCAAUAUG    0.3％

2513  2513 GCGAUUUGAAGCAAUAUGA    92.3％   7708  2517 AGCGAUUUaAAGCAAUAUG    0.4％

7659  2513 GCGAUUUGAAGCAgUAUGA    0.4％    7709  2517 AGCGAUUUGAAaCAAUAUG    0.2％

7660  2513 GuGAUUUGAAGCAAUAUGA    0.6％    7710  2517 AGCGAUUUGAAGCAAUAcG    0.5％

7661  2513 GCGAcUUGAAGCAAUAUGA    0.4％    7711  2517 AGCAUUUGAUAGCAAUAUa    0.4％

7662  2513 GCGAUcUGAAGCAAUAUGA    0.3％    7712  2517 gGCGAcUUGAAGCAAUAUG    0.3％

7663  2513 GCGAUUUaAAGCAAUAUGA    0.4％    7713  2517 AGCGAcUUGAAGCAAUAUu    0.1％

7664  2513 GCGAUUUGAAaCAAUAUGA    0.2％    2518  2518 GUCGAAAGAGGCGUAAGAA    91.8％

7665  2513 GCGAUUUGAAGCAAUAcGA    0.5％    7714  2518 GUCCGAAAGAGGCGAAGAg    0.9％

7666  2513 GCGAUUUGAAGCAAUAUaA    0.4％    7715  2518 GUCCGAAAGAGGCGAgGAA    0.2％

7667  2513 GCGAcUUGAAGCAAUAUuA    0.1％    7716  2518 GUCCGAgAGAGGCGAAGAA    1.3％

2514  2514 CUUUCGUCAGUCCGAAAGA    92.3％   7717  2518 GUCuGAAAGAGGCGAAGAA    0.2％

7668  2514 CUUUCGUCAGUCCGAgAGA    4.1％    7718  2518 GUCCGAgAGAGGCGAAGAg    2.5％

7669  2514 CUUUCGUCAGUCuGAAAGA    0.2％    7719  2518 aUCCGAAAGAGGCGAAGAA    0.6％

7670  25l4 uUUACGUCAGUCCGAAAGA    0.1％    7720  2518 GUCaGAAAGAGGCGAAGAA    0.1％

7671  2514 CUUUCaUCAGUCCGAAAGA    0.2％    7721  2518 GUCCGAAAGAGGCGAAaAA    0.1％

7673  2514 CUUUCGcCAGUCCGAAAGA    0.2％    7722  2518 aUCCGAAAGAGGCGAAGAg    0.3％

7673  2514 CUUUCGUCAaUCCGAAAGA    1.0％    7723  2518 aUCCGAgAGAGGCGAAGAg    1.7％

7674  2514 CUUUCGUCAGUCaGAAAGA    0.1％    7724  2518 GUCCGAgAGAGGaGAAGAg    0.3％

7675  2514 CUUUCGUCuGUCCGAAAGA    0.1％    2519  2519 GGCAAGCUUUCUCAAAUGU    91.5％

7676  2514 CUUUCGUCAaUCCGAgAGA    1.7％    7725  2519 GGCAAGCUUUCUCAgAUGU    0.1％

2515  2515 AAGCGAUUUGAAGCAAUAU    92.1％   7726  2519 GGuAAGCcUUCUCAAAUGU    0.1％

7677  2515 AAGCGAUUUGAAGCAgUAU    0.4％    7727  2519 GGCAAaCUUCUCAAAUUGU    0.2％

7678  2515 AAGuGAUUUGAAGCAAUAU    0.3％    7728  2519 GGCAAGCUgUCUCAAAUGU    0.3％

7679  2515 AgGCGAUUUGAAGCAAUAU    0.3％    7729  2519 GGCAAGCUUUCaCAAAUAU    7.7％

7689  2515 gAGCGAUUUGAAGCAAUAU    0.1％    7730  2519 GGuAAGCUUUCaCAAAUGU    0.1％

7681  2515 AgGuGAUUUGAAGCAAUAU    0.3％    2520  252O ACAUUCUUUGGAUGGAAAG    91.3％

7682  2515 AAGCGAcUUGAAGCAAUAU    0.2％    7731  2520 ACAUUCUUUGGAUGGAAgG    1.1％

7732  2520 ACAUUCUUUGGgUGGAAAG    0.1％    7781  2525 AUUUaAAGCAAUAUGAUAG    0.4％

7733  2520 ACAUUuUUUGGAUGGAAAG    2.3％    7782  2525 AUUUGAAaCAAUAUGAUAG    0.2％

7734  2520 ACgUUCUUUGGAUGGAAAG    0.6％    7783  25Z5 AUUUGAAGCAAUAcGAUAG    0.5％

7735  2520 ACAUUCUUUGGgUGGAAgG    0.1％    7784  2525 AUUUGAAGCAAUAUaAUAG    0.4％

7736  2520 ACAUUCUUcGGAUGGAAAG    0.1％    7785  2525 AUUUAAAGCAAUAUGAcAG    1.8％

7737  2520 ACAAUUCUUGGAUGGAAga    0.2％    7786  2525 AcUUGAAUCAAUAUuAUAG    0.1％

7738  2530 ACAUUCUUUGGcUGGAgAG    2.0％    2526  2526 AUUGAGGGCAAGCUUUCUC    91.2％

7739  2530 ACAUUuUUcGGAUGGAAAG    0.1％    7787  2526 AUUGAGGGuAAGCUUUCUC    0.1％

7740  2520 ACAUUCUUcGGcUGGAgAG    0.2％    7788  2526 AUaGAGGGCAAGCUUUCUC    0.1％

7741  2520 ACAUUuUUcGGcUGGAAAG    1.6％    7789  2526 AUUGAaGGCAAGCUUUCUC    0.3％

7742  2520 ACAUUuUUcGGuUGGAAAG    0.1％    7790  2526 AUUGAGGGCAAaCUUUCUC    0.2％

2521  2521 CAUUCUUUGGAUGGAAAGA    91.3％   7791  2526 AUUGAGGGCAAGCUgUCUC    0.3％

7743  2521 CAUUCUUUGGAUGGAAgGA    1.1％    7792  2526 AUUGAGGGCAAGCUUUCaC    7.7％

7744  2521 CAUUCUUUGGgUGGAAAGA    0.1％    7793  2526 AUUGAGGGuAAGCUUUCaC    0.1％

7745  2521 CAUUuUUUGGAUGGAAAGA    2.3％    2527  2527 GAGGGCAAGCUUUCUCAAA    91.2％

774G  2521 CGUUCUUUGGAUGGAAAGA    0.6％    7794  2527 GAGGGCAAGCUUUCUCAgA    0.1％

7747  2521 CAUUCUUUGGgUGGAAgGA    0.1％    7795  2527 GAGGGuAAGCUUUCUCAAA    0.1％

7748  2521 CAUUCUUcGGAUGGAAAGA    0.1％    7796  2527 GAaGGCAAGCUUUCUCAAA    0.3％

7749  2521 CAUUCUUUGGAUGGAAgaA    0.2％    7797  2527 GAGGGCAAaCUUUCUCAAA    0.2％

7750  2521 CAUUCUUUGGcUGGAgAGA    2.0％    7798  2527 GAGGGCAAGCUgUCUCAAA    0.3％

7751  2521 CAUUuUUcGGAUGGAAAGA    0.1％    7799  2527 GAGGGCAAGCUUUCaCAAA    7.7％

7752  2521 CAUUCUUcGGcUGGAgAGA    0.2％    7800  2527 GAGGGuAAGCUUUCaCAAA    0.1％

7753  2521 CAUUuUUcGGcUGGAAAGA    1.6％    2528  2528 GGGCAAGCUUUCUCAAAUG    91.2％

7754  2521 CAUUuUUcGGuUGGAAAGA    0.1％    7801  2528 GGGCAAGCUUUCUCAgAUG    0.1％

2523  2522 GAUUUGAAGCAAUAUGAUA    91.2％   7802  2528 GGGuAAGCUUUCUCAAAUG    0.1％

7755  2522 GAUUUGAAGCAgUAUGAUA    0.4％    7803  2528 aGGCAAGCUUUCUCAAAUG    0.3％

7756  2522 GAcUUGAAGCAAUAUGAUA    0.4％    7804  2528 GGGCAAaCUUUCUCAAAUG    0.2％

7757  2522 GAUcUGAAGCAAUAUGAUA    0.3％    7805  2528 GGGCAAGCUgUCUCAAAUG    0.3％

7758  2522 GAUUUaAAGCAAUAUGAUA    0.4％    7806  2528 GGGCAAGCUUUCaCAAAUG    7.7％

7759  2522 GAUUUGAAaCAAUAUGAUA    0.2％    7807  2528 GGGuAAGCUUUCaCAAAUG    0.1％

776O  2522 GAUUUGAAGCAAUAcGAUA    0.5％    2529  2529 CAUUGAGGGCAAGCUUUCU    91.2％

7761  2522 GAUUUGAAGCAAUAUaAUA    0.4％    7808  2529 CAUUGAGGGuAAGCUUUCU    0.1％

7762  2522 GAUUUGAAGCAAUAUGAcA    1.8％    7809  2529 CAUaGAGGGCAAGCUUUCU    0.1％

7763  2532 GAcUUGAAGCAAUAUuAUA    0.1％    7810  2529 CAUUGAaGGCAAGCUUUCU    0.3％

2523  2533 AGGGCAAGCUUUCUCAAAU    91.2％   7811  2529 CAUUGAGGGCAAaCUUUCU    0.2％

7764  2523 AGGGCAAGCUUUCUCAgAU    0.1％    7812  2529 CAUUGAGGGCAAGCUgUCU    0.3％

7765  2523 AGGGuAAGCUUUCUCAAAU    0.1％    7813  2529 CAUUGAGGGCAAGCUUUCa    7.7％

7766  2523 AaGGCAAGCUUUCUCAAAU    0.3％    7814  2529 CAUUGAGGGuAAGCUUUCa    0.1.％

7767  2523 AGGGCAAaCUUUCUCAAAU    0.2％    2530  2530 GGAAGCUUUCUCAAAUGUC    91.0％

7768  2523 AGGGCAAGCUgUCUCAAAU    0.3％    7815  2530 GCAAGCUUUCUCAAAUGUu    0.1％

7769  2533 AGGGCAAGCUUUCaCAAAU    7.7％    7816  2530 GCAAGCUUUCUCAgAUGUC    0.1％

7770  2523 AGGGuAAGCUUCaCAAAAU    0.1％    7817  2530 GuAAGCUUUCUCAAAUGUC    0.1％

2524  2534 UUGAGGGCAAGCUUUCUCA    91.2％   7818  2530 GCAAaCUUUCUCAAAUGUC    0.2％

7771  2534 UUGAGGGuAAGCUUUCUCA    0.1％    7819  2530 GCAAGCUgUCUCAAAUGUC    0.3％

7772  2524 UaGAGGGCAAGCUUUCUAA    0.1％    7820  2530 GCAAGCUUUCaCAAAUGUC    7.7％

7773  2524 UUGAaGGCAAGCUUUCUCA    0.3％    7821  2530 GCAAGCUUUCUCAAAUGUa    0.3％

7774  2524 UUGAGGGCAAaCUUUCUCA    0.2％    7822  2530 GUAAGCUUUCaCAAAUGUC    0.1％

7775  2524 UUGAGGGCAAGCUgUCUCA    0.3％    2531  2531 UGAGGGCAAGCUUUCUCAA    91.0％

7776  2534 UUGAGGGCAAGCUUUCaCA    7.7％    7823  2531 UGAGGCAAGCUUUUCUCAg    0.1％

7777  2534 UUGAGGGuAAGCUUUCaCA    0.1％    7824  2531 UGAGGGuAAGCUUUCUCAA    0.1％

2525  2535 AUUUGAAGCAAUAUGAUAG    91.2％   7825  2531 aGAGGGCAAGCUUUCUCAA    0.1％

7778  2525 AUUUGAAGCAgUAUGAUAG    0.4％    7826  2531 UGAaGGCAAGCUUUCUCAA    0.3％

7779  2525 AcUUGAAGCAAUAUCAUAG    0.4％    7827  2531 UGAGGGCAAaCUUUCUCAA    0.2％

7780  2525 AUcUGAAGCAAUAUGAUAG    0.3％    7828  2531 UGAGGGCAAGCUgUCUCAA    0.3％

7829  2531 UGAGGGCAAGCUUUCaCAA    7.7％    7878  2536 CGAUcUGAAGCAAUAUGAU    0.3％

7830  2531 UGAGGGuAAGCUUUCaCAA    0.1％    7879  2536 CGAUUUaAAGCAAUAUGAU    0.4％

2532  2532 CAGAAUGAGUUCAACAAGG    91.0％   7880  2536 CGAUUUGAAaCAAUAUGAU    0.2％

7831  2532 CAGAAUGAGUUCAAuAAGG    0.2％    7881  2536 CGAUUUGAAGCAAUAcGAU    0.5％

7832  2532 CAGAAUGAGUUuAACAAGG    0.3％    7882  2536 CGAUUUGAAGCAAUAUaAU    0.4％

7833  2532 CAGAgUGAGUUCAACAAGG    1.5％    7883  2536 CGAUUUGAAGCAAUAUGAc    1.8％

7834  2532 CAaAAUGAGUUCAACAAGG    0.2％    7884  2536 CGAcUUGAAGCAAUAUuAU    0.1％

7835  2532 CAGAAUGAaUUCAACAAGG    3.3％    2537  2537 UCUUUGGAUGGAAAGAACC    90.5％

7836  2532 CAGAAUGAGUUCAACAAaG    1.2％    7885  2537 UCUUUGGAUGGAAAGAgCC    1.4％

7837  2532 CAGAuUGAGUUCAACAAGG    0.1％    7886  2537 UCUUUGGAUGGAAgGAACC    1.1％

7838  2532 CAGAAUGgaUUCAACAAGG    0.1％    7887  2537 UCUUUGGgUGGAAGAAACC    0.1％

7839  2532 CAGAgUGAaUUCAACAAGG    2.0％    7888  2537 UuUUUGGAUGGAAAGAACC    2.3％

2533  2533 AGAAUGAGUUCAACAAGGC    91.0％   7889  2537 UCUUUGGgUGGAAgGAACC    0.1％

7840  2533 AGAAUGAGUUCAAuAAGGC    0.2％    7890  2537 UCUUcGGAUGGAAAGAACC    0.2％

7841  2533 AGAAUGAGUUuAACAAGGC    0.3％    7891  2537 UCUUUGGAUGGAAgAAACC    0.2％

7842  2533 AGAgUGAGUUCAACAAGGC    1.5％    7892  2537 UCUUUGGcUGGAgAGAgCC    2.0％

7843  2533 AaAAUGAGUUCAACAAGGC    0.2％    7893  2537 UuUUcGGAUGGAAAGAgCC    0.1％

7844  2533 AGAAUGAaUUCAACAAGGC    3.3％    7894  2537 UuUUcGGcUGGAAAGAACC    0.7％

7845  2533 ACAAUGAGUUCAACAAaGC    1.2％    2538  2538 AGCCUAUGUGGAUGGAUUC    90.4％

7846  2533 AGAuUGAGUUCAACAAGGC    0.1％    7895  2538 AGCCUAUGUGGAUGGAUUu    7.9％

7847  2533 AGAAUGgaUUCAACAAGGC    0.1％    7896  2538 AGCCUAUGUGGAUGGgUUC    0.6％

7848  2533 AGAgUGAaUUCAACAAGGC    2.0％    7897  2538 AaCCUAUGUGGAUGGAUUC    0.5％

2534  2534 AUAAGCGAUUUGAAGCGAAU   90.7％   7898  2538 AGCCUAUGUaGAUGGAUUC    0.2％

7849  2534 AUAAGCGAUUUGAAGCAgU    0.4％    7899  2538 AGCCUAUGUGGAUaGAUUC    0.1％

7850  2534 AUAAGuGAUUUGAAGCAAU    0.3％    7900  2538 AGCCUAUGUGGAUGGAUaC    0.1％

7851  2534 AUAgGCGAUUUGAAGCAAU    0.2％    7901  2538 AaCCUAUGUGGAUGGAUUu    0.1％

7852  2534 AUgAGCGAUUUGAAGCAAU    0.1％    2539  2539 CAAUGAAAGAGUAUGGAGA    90.4％

7853  2534 gUAAGCGAUUUGAAGCAAU    1.7％    7902  2539 CAAUGAAAGAGUAUGGgGA    4.1％

7854  2534 gUAgGCGAUUUGAAGCAAU    0.1％    7903  2539 CgAUGAAAA3AGAUGGAGA    0.％

7855  2534 gUAgGuGAUUUGAAGCAAU    0.3％    7904  2539 GAAUGAAgGAGUAUGGgGA    0.3％

7856  2534 AcAAGCGAUUUGAAGCAAU    0.2％    7905  2539 CAAUGAAAGAaUAUGGAGA    2.1％

7857  2534 AUAAGCGAcUUGAAGCAAU    0.1％    7906  2539 CAAUGAAAGAGUAcGGAGA    0.1％

7858  2534 AUAAGCGAUUUaAAGCAAU    0.3％    7907  2539 CAAUGAAAGAGUuUGGAGA    0.1％

7859  2534 AUAAGCGAUUUGAAaCAAU    0.2％    7908  2539 CAAUGAAAGAaUAUGGgGA    1.6％

7860  2534 AUuAGCGAUUUGAAGCAAU    0.2％    7909  2539 CAAUGAAgGAaUAUGGgGA    0.3％

7861  2534 AUAgGCGAcUUGAAGCAAU    0.3％    7910  2539 CAAUGAAgGAGUAcGGgGA    0.6％

7862  2534 gUAAGCGAcUUGAAGCAAU    0.1％    7911  2539 CAAUGAAAGAacAUGGAGA    0.1％

7863  2534 gUAAGCGAUcUGAAGCAAU    0.3％    2540  2540 GGAAGCAAUAUGAUAGUGA    90.2％

7864  2534 AUcAGCGAUUUaAAGCAAU    0.1％    7912  2540 UGAAGCAgUAUGAUAGUGA    0.4％

2535  2535 UUCUUUGGAUGGAAAGAAC    90.5％   7913  2540 UaAAGCAAUAUGAUAGUGA    0.4％

7865  2535 UUCUUUGGAUGGAAAGAgC    1.4％    7914  2540 UGAAaCAAUAUGAUAGUGA    0.2％

7866  2535 UUCUUUGGAUGGAAgGAAC    1.1％    7915  2540 UGAAGCAAUAcGAUAGUGA    0.5％

7867  2535 UUCUUUGGgUGGAAAGAAC    0.1％    7916  2540 UGAAGCAAUAUaAUAGUGA    0.4％

7868  2535 UUuUUUGGAUGGAAAGAAC    2.3％    7917  2540 UGAAGCAAUAUGAcAGUGA    1.6％

7869  2535 UCUUUGGgUGGAAgGAAAC    0.1％    7918  2540 UGAAGCAAUAUGAUAGcGA    1.6％

7870  2535 UUCUUcGGAUGGAAAGAAC    0.1％    7919  2540 UGAAGCAAUAUGAUAGUaA    0.1％

7871  2535 UUOUUUGGAUGGAAgaAAC    0.2％    7920  2540 UGAAGCAAUAUuAUAGUGA    0.1％

7872  2535 UUCUUUGGcUGGAgAGAgC    2.0％    7921  2540 UGAAGCAAUAUGAcAGcGA    0.2％

7874  2535 UUuUUcGGAUGGAAAGAgC    0.1％    2541  2541 UGGAAGAUUUUGUGCGACA    90.1％

7874  2535 UUuUUcGGcUGGAAAGAAC    0.7％    7922  2541 UGGAAGAUUUUGUGCGgCA    0.2％

2535  2536 CGAUUUGAAGCAAUAUGAU    90.5％   7923  2541 UGGAgGAUUUUGUGCGACA    0.2％

7875  2536 CGAUUUGAAGCAgUAUGAU    0.4％    7924  2541 UGGAAGAaUUUGUGCGACA    0.3％

7876  2536 uGAUUUGAAGCAAUAUGAU    0.6％    7925  2541 UGGAAGAcUUUGUGCGACA    3.4％

7877  2536 CGAcUUGAAGCAAUAUGAU    0.4％    7926  2541 UGGAAGAUUUcGUGCGACA    0.1％

7927  2541 UGGAAGAUUUUGUaCGACA    1.6％    7951  2543 AAAGAGUUcUUUGAGAAcA    0.3％

7928  2541 UGGAAGAUUUUGUGaGACA    0.1％    7952  2543 AAAGAGUUUUUcaAGAAUA    0.2％

7929  2541 UGGAAGAUUUUGUGgGACA    0.1％    2544  2544 UAAUGAAGGGGGUAUAGAU    90.0％

7930  2541 UGGAAGAcUgUGUGCGACA    0.1％    7953  2544 UAAUGAAGGGGGUAUACgU    0.7％

7931  2541 UGGAAGAUUUUGaGgGACA    0.1％    7954  2544 UAAUGAAGGGGGUgUACAU    00.6％

2542  2542 AUGGAAGAUUUUGUGCGAC    90.1％   7955  2544 UAgUGAAGGGGGUAUACAU    0.1％

7932  2542 AUGGAAGAUUUUGUGCGgC    0.2％    7956  2544 UAAUGAAaGGGGUAUACAU    0.2％

7933  2542 AUGGAgGAUUUGUGGCGAC    0.2％    7957  2544 UAAUGAAGGGaGUAUACAU    3.8％

7934  2542 AUGGAAGAaUUUGUGCGAC    0.3％    7958  2544 UAAUGAAGGGGaUAUACAU    0.1％

7935  2542 AUGGAAGAcUUUGUGCGAC    3.4％    7959  2544 UAAUGAAGGGGGUuUACAU    2.2％

7936  2542 AUGGAAGAUUUcGUGCGAC    0.1％    7960  2544 UAAUGAAGGGaGUgUACAU    2.0％

7937  2542 AUGGAAGAUUUUGUaCGAC    1.6％    7961  2544 UAAUGAAGGGaaUAUACAU    0.1％

7938  2542 AUGGAAGAUUUUGUGaGAC    0.1％    2545  2545 GAAGAAUUUUGUGCACAAU    90.0％

7939  2542 AUGGAAGAUUUUGUGgGAC    0.1％    7962  2545 GAAGAUUUUGUGCGACAgU    0.9％

7940  2542 AUGGAAGAcUgUGUGCGAC    0.1％    7963  2545 GAAGAUUUUGUGCGgCAAU    0.2％

7941  2542 AUGGAAGAUUUUGaGgGAC    0.1％    7964  2545 GAgGAUUUUGUGCGACAAU    0.2％

2543  2543 AAAGAGUUUUUUGAGAAUA    90.1％   7965  2545 GAAGAaUUUGUGCGACAAU    0.3％

7942  2543 AAAGAGUUUUUUGAGAgUA    0.4％    7966  2545 GAAGAcUUUGUGCGACAAU    3.1％

7943  2543 AAAGAGUUUUUUGAGgAUA    0.2％    7967  2545 GAAGAUUUcGUGCGACAAU    0.1％

7944  2543 AAgGAGUUUUUUGAGAAUA    0.1％    7968  2545 GAAGAUUUUGUaCGACAAU    1.6％

7945  2543 AAAGAaUUUUUUGAGAAUA    0.3％    7969  2545 GAAGAUUUUGUGaGACAAU    0.1％

7946  2543 AAAGAGUUUUUcGAGAAUA    1.5％    7970  2545 GAAGAUUUGUUGgGACAAU    0.1％

7947  2543 AAAGAGUUUUUUGAaAAUA    0.5％    7971  2545 GAAGAcUUUGUGCGACAgU    0.3％

7948  2543 AAAGAGUUUUUUGAGAAcA    1.6％    7972  2545 GAAGAcUgUGUGCGACAAU    0.1％

7949  2543 AAAGAuUUUUUUGAGAAUA    0.2％    7973  2545 GAAGAUUUUGaGgGACAAU    0.1％

7950  2543 AAAGnGUUUUUUGAGAAUA    0.1％

表20-4.从表1-5所列甲型流感片段5(NP)序列得到的保守和小变体19-mer序列。保守序列匹配所列病毒序列的至少89％，变体含有从参考序列的3个或更少核苷酸变化。

SeQ ID RefID    匹配序列             ％总数      7988  3549    UUAUUUCUUCGGgGAuAAU    0.1％

3546   3546    UCUUAUUUCUUCGGAGACA    98.0％     3550  3550    CUUAUUUCUUCGGAGACAA    97.9％

7974   3546    UCUUAUUUCUUCGGgGACA    1.6％      7989  3550    CUUAUUUCUUCGGAGACAg    0.1％

7975   3546    UCUUAUUUCUUuGGAGACA    0.2％      7990  3550    CUUAUUUCUUCGGgGACAA    1.6％

7976   3546    UCUUAUUUCUUCGGgGAuA    0.1％      7991  3550    CUUAUUUCUUuGGAGACAA    0.2％

3547   3547    AUUUCUUCGGAGACAAUGC    97.9％     7992  3550    CUUAUUUCUUCGGgGAuAA    0.1％

7977   3547    AUUUCUUCGGAGACAgUGC    0.1％      3551  3551    UUUCUUCGGAGACAAUGCA    97.8％

7978   3547    AUUUCUUCGGgGACAAUGC    1.6％      7993  3551    UUUCUUCGGAGACAgUGCA    0.1％

7979   3547    AUUUCUUuGGAGACAAUGC    0.2％      7994  3551    UUUCUUCGGgGACAAUGCA    1.6％

7980   3547    AUUUCUUCGGgGAuAAUGC    0.1％      7995  3551    UUUCUUuGGAGACAAUGCA    0.2％

3548   3548    UAUUUCUUCGGAGACAAUG    97.9％     7996  3551    UUUCUUCGGgGAuAAUGCA    0.1％

7981   3548    UAUUUCUUCGGAGACAgUG    0.1％      3552  3552    AUGAAGAUCUUAUUUCUUU    97.6％

7982   3548    UAUUUCUUCGGgGACAAUG    1.6％      7997  3552    AUGAAGGgUCUUAUUUCUU    0.7％

7983   3548    UAUUUCUUuGGAGACAAUG    0.2％      7998  3552    AUGAgGGAUCUUAUUUCUU    0.2％

7984   3548    UAUUUCUUUCGGgGAuAUG    0.1％      7999  3552    AUGAgGGgUCUUAUUUCUU    0.2％

3549   3549    UUAUUUCUUCGGAGACAAU    97.9％     8000  3552    AcGAAGGAUCUUAUUUCUU    0.1％

7985   3549    UUAUUUCUUCGGAGACAgU    0.1％      8001  3552    AUGAAGGuUCUUAUUUCUU    1.1％

7986   3549    UUAUUUCUUCGGgGACAAU    16％       3553  3553    AAUUGAAGGAUCUAUUUCU    97.6％

7987   3549    UUAUUUCUUuGGAGACAAU    0.2％      8002  3553    AAUGAAGGgUCUUAYUUCU    0.7％

8003  3553    AAUGAgGGAUCUUAUUUCU    0.2％    8046  3561    GGAUCUUAUUUCUUuGGAG    0.2％

8004  3553    AAUGAgGGgUCUUAUUUCU    0.1％    8047  3561    GGgUCUUAUUUCUUCGGAG    0.9％

8005  3553    AAcGAAGGAUCUUAUUUCU    0.1％    8048  3561    GGuUCUUAUUUCUUCGGAG    1.1％

8006  3553    AAUGAAGGuUCUUAUUUCU    1.1％    3562  3562    AUCUUAUUUCUUCGGAGAC    96.0％

8007  3553    uAUGAgGGgUCUUAUUUCU    0.1％    8049  3562    AUCUUAUUUCUUCGGgGAC    1.6％

3554  3554    GAAGGAUCUUAUUCUUCG     97.5％   8050  3562    AUCUUAUUUCUUuGGAGAC    0.2％

8008  3554    GAAGGAUCUUAUUUCUUuG    0.2％    8051  3562    gUCUUAUUUCUUCGGAGAC    0.9％

8009  3554    GAAGGgUCUUAUUUCUUCG    0.7％    8052  3562    AUCUUAUUUCUUCGGgGAu    0.1％

8010  3554    GAgGGAUCUUAUUUCUUCG    0.2％    8053  3562    uUCUUAUUUCUUCGGAGAC    1.1％

8011  3554    GAgGGgUCUUAUUUCUUCG    0.2％    3563  3563    AGGAUCUUAUUUCUUCGGA    95.8％

8012  3554    GAAGGuUCUUAUUUCUUCG    1.1％    8054  3563    AGGAUCUUAUUUCUUCGGg    1.7％

3555  3555    AAGGAUCUUAUUUCUUCGG    97.5％   8055  3563    AGGAUCUUAUUUCUUuGGA    0.2％

8013  3555    AAGGAUCUUAUUUCUuGG     0.2％    8056  3563    AGGgUCUUAUUUCUUCGGA    0.7％

8014  3555    AAGGgUCUUAUUUCUUCGG    0.7％    8057  3563    gGGAUCUUAUUUCUUCGGA    0.2％

8015  3555    AgGGAUCUUAAUUCUUCGG    0.2％    8058  3563    gGGgUCUUAUUUCUUCGGA    0.2％

8016  3555    AgGGgUCUUAUUUCUUCGG    0.2％    8059  3563    AGGuUCUUAUUUCUUCGGA    1.1％

8017  3555    AAGGuUCUUAUUUCUUCGG    1.1％    3564  3564    AGUAAUGAAGGAUCUUAUU    95.4％

3556  3556    UGAAGGAUCUUAUUUCUUC    97.4％   8060  3564    AGUAAUGAAGGgUCUUAUU    0.7％

8018  3556    UGAAGGAUCUUAUUUCUUu    0.2％    8061  3564    AGUAAUGAgGGAUCUUAUU    0.2％

8019  3556    UGAAGGgUCUUAUUUCUUC    0.7％    8062  3564    AaUAAUGAAGGAUCUUAUU    1.9％

8020  3556    UGAgGGAUCUUAUUUCUUC    0.2％    8063  3564    AGcAAUGAAGGAUCUUAUU    0.3％

8021  3556    UGAgGGgUCUUAUUUCUUC    0.2％    8064  3564    AGUAAcGAAGGAUCUUAUU    0.1％

8022  3556    cGAAAGGAUCUUAUUUCUUC   0.1％    8065  3564    AGUAAUGAAGGuUCUUAUU    1.1％

8023  3556    UGAAGGuUCUUAUUUCUUC    1.1％    8066  3564    AaUAAUGAgGGgUCUUAUU    0.1％

3557  3557    UAAUGAAGGAUCUUAUUUC    97.3％   3565  3565    GUAAUGAAGGAUCUUAUUU    95.4％

8024  3557    UAAUGAAGGgUCUUAUUUC    0.7％    8067  3565    GUAAUGAAGGgUCUUAUUU    0.7％

8025  3557    UAAUGAgGGAUCUUAUUUC    0.2％    8068  3565    GUAAUGAgGGAUCUUAUUU    0.2％

8026  3557    UAAUGAgGGgUCUUAUUUC    0.1％    8069  3565    aUAAUGAAGGAUCUUAUUU    1.9％

8027  3557    cAAUGAAGGAUCUUAUUUC    0.3％    8070  3565    GcAAUGAAGGAUCUUAUUU    0.3％

8028  3557    UAAcGAAGGAUCUUAUUUC    0.1％    8071  3565    GUAAcGAAGGAUCUUAUUU    0.1％

8029  3557    UAAUGAAGGuUCUUAUUUC    1.1％    8072  3565    GUAAUGAAGGuUCUUAUUU    1.1％

8030  3557    UuAUGAgGGgUCUUAUUUC    0.1％    8073  3565    aUAAUGAgGGgUCUUAUUU    0.1％

3558  3558    UUCUUCGGAGACAAUGCAG    96.5％   3566  3566    AUGAGUAAUGAAGGAUCUU    95.3％

8031  3558    UUCUUCGGAGACAgUGCAG    0.1％    8074  3566    AUGAGUAAUGAAGGgUCUU    0.7％

8032  3558    UUCUUCGGgGACAAUGCAG    1.6％    8075  3566    AUGAGUAAUGAgGGAUCUU    0.2％

8033  3558    UUCUUuGGAGACAAUGCAG    0.2％    8076  3566    AUaAGUUAAUGAGGAUCUU    0.2％

8034  3558    UUCUUCGGgGAuAAUGCAG    0.1％    8077  3566    AUGAaUAAUGAAGGAUCUU    1.9％

8035  3558    UUCUUCGGAGACAAUGCAa    0.3％    8078  3566    AUGAGcAAUGAAGGAUCUU    0.3％

3559  3559    UCUUCGGAGACAAUGCAGA    96.4％   8079  3566    AUGAGUAAcGAAGGAUCUU    0.1％

8036  3559    UCUUCGGAGACAgUGCAGA    0.1％    8080  3566    AUGAGUAAUGAAGGuUCUU    1.1％

8037  3559    UCUUCGGgGACAAUGCAGA    1.6％    8081  3566    AUGAaUAAUGAgGGgUCUU    0.1％

8038  3559    UCUUuGGAGACAAUGCAGA    0.2％    3567  3567    UGAGUAAUGAA  AUCUUA    95.3％

8039  3559    UCUUCGGgGAuAAUGCAGA    0.1％    8082  3567    UGAGUAAUGAAGGgUCUUA    0.7％

8040  3559    UCUUCGGAGACAAUGCAaA    0.3％    8083  3567    UGAGUAAUGAgGGAUCUUA    0.2％

3560  3560    GAUCUUAUUUCUUCGGAGA    96.0％   8084  3567    UaAGUAAUGAAGGAUCUUA    0.2％

8041  3560    GAUCUUAUUUCUUCGGgGA    1.7％    8085  3567    UGAaUAAUGAAGGAUCUUA    1.9％

8042  3560    GAUCUUAUUUCUUuGGAGA    0.2％    8086  3567    UGAGcAAUGAAGGAUCUUA    0.3％

8043  3560    GgUCUUAUUUCUUCGGAGA    0.9％    8087  3567    UGAGUAAcGAAGGAUCUUA    0.1％

8044  3560    GuUCUUAUUUCUUCGGAGA    1.1％    8088  3567    UGAGUAAUGAAGGuUCUUA    1.1％

3561  3561    GGAUCUUAUUUCUUCGGAG    96.0％   8089  3567    UGAaUAAUGAgGGgUCUUA    0.1％

8045  3561    GGAUCUUAUUUCUUCGGgG    1.7％    3568  3568    GAGUAAUGAAGGAUCUUAU    95.3％

8090  3568  GAGUAAUGAAGGgUCUUAU  0.7％    8137  3572  GUgCAAAUUGCUUCAAAUG    0.1％

8091  3568  GAGUAAUGAgGGAUCUUAU  0.2％    8138  3572  aUACAAAUUGCUUCAAAUG    0.4％

8092  3568  aAGUAAUGAAGGAUCUUAU  0.2％    8139  3572  GUACAAAUUGCcUCAAAUG    0.1％

8093  3568  GAaUAAUGAAGGAUCUUAU  1.9％    8140  3572  GUACAAAUUGCUUCAAAcG    0.1％

8094  3568  GAGcAAUGAAGGAUCUUAU  0.3％    8141  3572  GUuCAAAUUGCUUCAAAUG    2.1％

8095  3568  GAGUAAcGAAGGAUCUUAU  0.1％    8142  3572  GUuCAgAUUGCUUCAAAUG    2.5％

8096  3568  GAGUAAUGAAGGuUCUUAU  1.1％    8143  3572  aUuCAAAUUGCUUCAAAUG    0.2％

8097  3568  GAaUAAUGAgGGgUCUUAU  0.1％    8144  3572  GUuCAAAUaGCUUCAAAUG    0.2％

3569  3569  UACAAAUUGCUUCAAAUGA  93.7％   8145  3572  GUuCAAAUUGCUUCcAAUG    0.5％

8098  3569  UACAgAUUGCUUCAAAUGA  0.1％    8146  3572  aUuCAgAUUGCUUCAAAUG    0.1％

8099  3569  UgCAAAUUGCUUCAAAUGA  0.1％    8147  3572  GUuCAgAUUGCgUCAAAUG    0.3％

8100  3569  UACAAAUUGCcUCAAAUGA  0.1％    8148  3572  GUuCAgAUUGCUUCcAAUG    0.1％

8101  3569  UACAAAUUGCUUCAAAcGA  0.1％    3573  3573  AUGGGUGCUCUCUGCUUUG    93.3％

8102  3569  UuCAAAUUGCUUCAAAUGA  2.3％    8149  3573  AUGGUGCUuUCUGCUUUUG    0.2％

8103  3569  UuCAgAUUGCUUCAAAUGA  2.6％    8150  3573  AUGGUaCUCUCUGCUUUUG    0.8％

8104  3569  UuCAAAUaGCUUCAAAUGA  0.2％    8151  3573  AUGGUGCUaUCUGCUUUUG    0.1％

8105  3569  UuCAAAUUGCUUCcAAUGA  0.5％    8152  3573  AUGGUGCUCUCaGCUUUUG    0.1％

8106  3569  UuCAgAUUGCgUCAAAUGA  0.3％    8153  3573  AUGGUGCUCUCUGCcUUUG    1.1％

8107  3569  UuCAgAUUGCUUCcAAUGA  0.1％    8154  3573  AUGGUGCUCUCUGCgUUUG    0.1％

3570  3570  AAUUUCAAACAGCUGCACA  93.5％   8155  3573  AUGGUGCUCUCUGCUUUcG    0.2％

8108  3570  AAUUUCAAACAGCUGCgCA  0.3％    8156  3573  AUGGUaCUCUCUGCaUUUG    1.7％

8109  3570  AAUUUCAAACgGCUGCACA  04％     8157  3573  AUGGUcCUCUCUGCaUUUG    0.2％

8110  3570  AAUUUCAAgCAGCUGCACA  0.1％    8158  3573  AUGGUuCUCUCUGCaUUUG    1.9％

8111  3570  AAUUUCAgACAGCUGCACA  0.3％    3574  3574  UGGUGCUCUCUGCUUUUGA    93.3％

8112  3570  AAcUUCAAACAGCUGCACA  0.2％    8159  3574  UGGUGCUuUCUGCUUUGGA    0.2％

8113  3570  AAUUcCAAACAGCUGCACA  0.1％    8160  3574  UGGUaCUCUCUGCUUUUGA    0.8％

8114  3570  AAUUUCAAACAGCaGCACA  2.1％    8161  3574  UGGUGCUaUCUGCUUUUGA    0.1％

8115  3570  AAUUUCAAACAGCUGCuCA  0.1％    8162  3574  UGGUGCUCUCaGCUUUUGA    0.1％

8116  3570  AAUUUCAAACuGCUGCACA  0.5％    8163  3574  UGGUGCUCUCUGCcUUUGA    1.1％

8117  3570  AAUUUCAAACgGCaGCACA  0.1％    8164  3574  UGGUGCUCUCUGCgUUUGA    0.1％

8118  3570  AAUUUCAgACAGCUGCcCA  0.3％    8165  3574  UGGUGCUCUCUGCUUUcGA    0.2％

8119  3570  AgUUUCAgACAGCUGCcCA  0.1％    8166  3574  UGGUaCUCUCUGCaUUUGA    1.7％

8120  3570  AAUUcCAAACAGCaGCACA  1.9％    8167  3574  UGGUcCUCUCUGCaUUUGA    0.2％

8121  3570  AAUUUCAgACcGCaGCACA  0.1％    8168  3574  UGGUuCUCUCUGCaUUUGA    1.9％

3571  3571  AAAUUUCAAACAGCUGCAC  93.5％   3575  3575  CAAGGCACCAAACGGUCUU    93.2％

8122  3571  AAAUUUCAAACAGCUGCgC  0.3％    8169  3575  CAAGGuACCAAACGGUCUU    0.1％

8123  3571  AAAUUUCAAACgGCUGCAC  0.4％    8170  3575  CAgGGCACCAAACGGUCUU    0.8％

8124  3571  AAAUUUCAAgCAGCUGCAC  0.1％    8171  3575  CAAGGCAaCAAACGGUCUU    0.1％

8125  3571  AAAUUUCAgACAGCUGCAC  0.3％    8172  3575  CAAGGCACCAAACGaUCUU    4.7％

8126  3571  AAAcUUCAAACAGCUGCAC  0.2％    8173  3575  CAAGGCACCAcACGGUCUU    0.1％

8127  3571  AAAUUcCAAACAGCUGCAC  0.1％    8174  3575  aAAGGCACCAAACGaUCUU    0.1％

8128  3571  AAAUUUCAAACAGCaGCAC  2.1％    8175  3575  CAAGGCACCAAACGaUCaU    0.7％

8129  3571  AAAUUUCAAACAGCUGCuC  0.1％    8176  3575  CAAGGCACCAAACGaUCcU    0.4％

8130  3571  AAAUUUCAAACuGCUGCAC  0.5％    3576  3576  AAGGCACCAAACGGUCUUA    93.2％

8131  3571  AAAUUUCAAACgGCaGCAC  0.1％    8177  3576  AAGGuACCAAACGGUCUUA    0.1％

8132  3571  AAAUUUCAgACAGCUGCcC  0.3％    8178  3576  AgGGCACCAAACGGUCUUA    0.8％

8133  3571  AAgUUUCAgACAGCUGCcC  0.1％    8179  3576  AAGGCAaCAAACGGUCUUA    0.1％

8134  3571  AAAUUcCAAACAGCaGCAC  1.9％    8180  3576  AAGGCACCAAACGaUCUUA    4.7％

8135  3571  AAAUUUCAgACcGCaGCAC  0.1％    8181  3576  AAGGCACCAcACGGUCUUA    0.1％

8572  3572  GUACAAAUUGCUUCAAAUG  93.4％   8182  3576  AAGGCACCAAACGaUCaUA    0.7％

8136  3572  GUACAgAUUGCUUCAAAUG  0.1％    8183  3576  AAGGCACCAAACGaUCcUA    0.4％

3577  3577    AGAGAAUGUGCAACAUUCU    93.0％   8230    3581    GGAACCCAGGgAAUGCUGA    0.6％

8184  3577    AGAGAAUGUGCAAuAUUCU    0.3％    8231    3581    GGAAuCCAGGAAAUGCUGA    1.2％

8185  3577    AGAGgAUGUGCAACAUUCU    0.5％    8232    3581    GaAACCCAGGAAAUGCUGA    0.4％

8186  3577    AaAGAAUGUGCAACAUUCU    1.2％    8233    3581    GGAACCCAaGAAAUGCUGA    0.1％

8187  3577    AGAGAUGUUGCAACAUcCU    4.0％    8234    3581    GGAACCCAGGAAAcGCUGA    0.9％

8188  3577    AuAGAUGUGCCAACAUUCU    0.3％    8235    3581    GGAACCCAGGAAAUaCUGA    0.1％

8189  3577    AaAGAAUGUGCAAuAUUCU    0.4％    8236    3581    GaAACCCAGGgAAUGCUGA    0.4％

8190  3577    AGAGAAUGUGCAACgUcCU    0.1％    8237    3581    GaAAuCCAGGgAAUGCUGA    0.1％

8191  3577    AGAGAAUGUGCAAuAUcCU    0.2％    8238    3581    GGAAuCCuGGgAAUGCUGA    0.2％

8192  3577    AGAGgAUGUGCAACAUcCU    0.1％    3582    3582    CGAACCCGAUCGUGCCCUC    92.1％

3578  3578    GAGAGAAUGUGCAACAUUC    93.0％   8239    3582    CGAACCCGAUCGUGCCuUC    5.1％

8193  3578    GAGAGAAUGUGCAAuAUUC    0.3％    8240    3582    CGAACCCGgUCGUGCCCUC    1.1％

8194  3578    GAGAGgAUGUGCAACAUUC    0.5％    8241    3582    CGAgCCCGAUCGUGCCCUC    0.1％

8195  3578    GAaAGAAUGUGCAACAUUC    1.2％    8242    3582    CGAgCCCGAUCGUGCCuUC    0.6％

8196  3578    GAGAGAAUGUGCAACAUcC    4.0％    8243    3582    CGAACCCaAUCGUGCCCUC    0.5％

8197  3578    GAuAGAAUGUGCAACAUUC    0.3％    8244    3582    CGAACCCcAUCGUGCCCUC    0.3％

8198  3578    GAaAGAAUGUGCAAuAUUC    0.4％    8245    3582    CGAACCCGAUCGUuCCCUC    0.1％

8199  3578    GAGAGAAUGUGCAACgUcC    0.1％    8246    3582    CGAACCCuAUCGUGCCCUC    0.1％

8200  3578    GAGAGAAUGUGCAAuAUcC    0.2％    3583    3583    CGGAACCCAGGAAAUGCUG    92.1％

8201  3578    GAGAGgAUGUGCAACAUcC    0.1％    8247    3583    CGGAACCCAGGgAAUGCUG    0.6％

3579  3579    AUUUCAAACAGCUGCACAA    92.7％   8248    3583    CGGAAuCCAGGAAAUGCUG    1.2％

8202  3579    AUUUCAAACAGCUGCACAg    0.9％    8249    3583    uGGAACCCAGGAAAUGCUG    0.1％

8203  3579    AUUUCAAACAGCUGCgCAA    0.3％    8250    3583    CGaAACCCAGGAAAUGCUG    0.4％

8204  3579    AUUUCAAACgGCUGCACAA    0.4％    8251    3583    GGGAACCCAaGAAAUGCUG    0.1％

8205  3579    AUUUCAAgCAGCUGCACAA    0.1％    8252    3583    CGGAACCCAGGAAAcGCUG    0.9％

8206  3579    AuUUCAgACAGCUGCACAg    0.3％    8253    3583    CGGAACCCAGGAAAUaCUG    0.1％

8207  3579    AcUUCAAACAGCUGCACAA    0.2％    8254    3583    CGaAACCCAGGgAAUGCUG    0.4％

8208  3579    AUUcCAAACAGCUGCACAA    0.1％    8255    3583    CGGAAuCCuGGgAAUGCUG    0.1％

8209  3579    AUUUCAAACAGCaGCACAA    2.1％    3584    3584    AAUGCUGAGAUCGAAGAUC    91.7％

8210  3579    AUUUCAAACAGCUGCuCAA    0.1％    8256    3584    AAUGCUGAGAUuGAAGAUC    1.3％

8211  3579    AUUUCAAACuGCUGCACAA    0.5％    8257    3584    AAcGCUGAGAUCGAAGAUC    0.2％

8212  3579    AUUUCAAACgGCaGCACAA    0.1％    8258    3584    AAUaCUGAGAUCGAAGAUC    0.1％

8213  3579    AUUUCAgACAGCUGCcCAg    0.3％    8259    3584    AAUGCUGAaAUCGAAGAUC    0.9％

8214  3579    AUUcCAAACAGCaGCACAA    1.9％    8260    3584    AAUGCUGAGAUaGAAGAUC    0.1％

8215  3579    AUUUCAgACcGCaGCACAA    0.1％    8261    3584    AAUGCUGAGuUCGAAGAUC    0.5％

3580  3580    UUUCAAACAGCUGCACAAA    92.7％   8262    3584    AAcGCUGAGAUuGAAGAUC    0.2％

8216  3580    UUUCAAACAGCUGCACAgA    0.9％    8263    3584    AAUGCUGAaAUuGAAGAUC    4.1％

8217  3580    UUUCAAACAGCUGCgCAAA    0.3％    8264    3584    AAUGCUGAGAUuGAAGAcC    0.2％

8218  3580    UUUCAAACgGCUGCACAAA    0.4％    8265    3584    AAUGCUGAGuaCGAAGAUC    0.1％

8219  3580    UUUCAAgCAGCUGCACAAA    0.1％    8266    3584    AAcGCUGAaAUuGAAGAUC    0.5％

8220  3580    UUUCAgACAGCUGCACAgA    0.3％    3585    3585    AUGCUGAGAUCGAAGAUCU    91.7％

8221  3580    cUUCAAACAGCUGCACAAA    0.2％    8267    3585    AUGCUGAGAUuGAAGAUCU    1.3％

8222  3580    UUcCAAACAGCUGCACAAA    0.1％    8268    3585    AcGCUGAGAUCGAAGAUCU    0.2％

8223  3580    UUUCAAACAGCaGCACAAA    2.0％    8269    3585    AUaCUGAGAUCGAAGAUCU    0.1％

8224  3580    UUUCAAACAGCUGCuCAAA    0.1％    8270    3585    AUGCUGAaAUCGAAGAUCU    0.9％

8225  3580    UUUCAAACuGCUGCACAAA    0.5％    8271    3585    AUGCUGAGAUaGAAGAUCU    0.1％

8226  3580    UUUCAAACgGCaGCACAAA    0.1％    8272    3585    AUGCUGAGuUCGAAGAUCU    0.5％

8227  3580    UUUCAgACAGCUGCcCAgA    0.4％    8273    3585    AcGCUGAGAUuGAAGAUCU    0.2％

8228  3580    UUcCAAACAGCaGCACAAA    1.7％    8274    3585    AUGCUGAaAUuGAAGAUCU    4.1％

8229  3580    UUUCAAACAGCaGCACAAc    0.1％    8275    3585    AUGCUGAGAUuGAAGAcCU    0.2％

3581  3581    GGAACCCAGAAAAUGCUGA    92.2％   8276    3585    AUGCUGAGuaCGAAGAUCU    0.1％

8277    3585    AcGCUGAaAUuGAAGAUCU    0.5％    8323    3590    ACCCAGGgAAUGCUGAGAU    0.6％

3586    3586    GAUUCUACAUCCAAAUGUG    91.6％   8324    3590    AuCCAGGAAAUGCUGAGAU    1.0％

8278    3586    GAUUCUACAUCCAgAUGUG    2.3％    8325    3590    ACCCAaGAAAUGCUGAGAU    0.1％

8279    3586    GAUUCUACAUuCAAAUGUG    0.9％    8326    3590    ACCCAGGAAAcGCUGAGAU    0.4％

8280    3586    GAUUCUAuAUCCAAAUGUG    0.5％    8327    3590    ACCCAGGAAAUaCUGAGAU    0.1％

8281    3586    GAUUuUACAUCCAAAUGUG    0.2％    8328    3590    ACCCAGGAAAUGCUGAaAU    1.0％

8282    3586    GgUUCUACAUCCAAAUGUG    0.3％    8329    3590    ACCCAGGgAAUGCUGAGuU    0.4％

8283    3586    aAUUCUACAUCCAAAUGUG    0.1％    8330    3590    AuCCAGGAAAUGCUGAaAU    0.1％

8284    3586    GAUUCUACAUaCAgAUGUG    0.1％    8331    3590    AuCCAGGAAAUGCUGAGuU    0.1％

8285    3586    GgUUCUACAUaCAgAUGUG    1.7％    8332    3590    AuCCAGGgAAUGCUGAaAU    0.1％

8286    3586    aAUUCUACAUaCAAAUGUG    0.2％    8333    3590    AuCCuGGgAAUGCUGAGAU    0.3％

3587    3587    GCUGAGAUCGAAGAUCUCA    91.5％   8334    3590    ACCCAGGAAAcGCUGAaAU    0.5％

8287    3587    GCUGAGAUuGAAGAUCUCA    1.4％    8335    3590    ACCCAGGAAAUGCUGAGua    0.1％

8288    3587    GCUGAGAUuGAAGAUCUuA    0.1％    8336    3590    ACCCAGGAAAUGCUGAaga    0.1％

8289    3587    aCUGAGAUCGAAGAUCUCA    0.1％    3591    3591    UCAGACAUGAGGGCAGAAA    91.4％

8290    3587    GCUGAaAUCGAAGAUCUCA    0.9％    8337    3591    UCAGACAUGAGGGCAGAgA    0.2％

8291    3587    GCUGAGAUaGAAGAUCUCA    0.1％    8338    3591    UCAGACAUGAGGGCgGAAA    0.1％

8292    3587    GCUGAGAUCGAAGAUCUaA    0.4％    8339    3591    UCAGAuAUGAGGGCAGAAA    0.4％

8293    3587    GCUGAGuUCGAAGAUCUCA    0.5％    8340    3591    UCgGACAUGAGGGCAGAAA    0.4％

8294    3587    GCUGAaAUuGAAGAUCUCA    4.4％    8341    3591    UCAGACAUGAGaGCAGAAA    1.4％

8295    3587    GCUGAaAUuGAAGAUCUuA    0.2％    8342    3591    UCAGACAUGAGGGCuGAAA    0.4％

8296    3587    GCUGAGAUuGAAGAcCUuA    0.2％    8343    3591    UCuGACAUGAGGGCAGAAA    0.3％

8297    3587    GCUGAGuaCGAAGAUCUCA    0.1％    3592    3592    UGCUGAGAUCGAAGAUCUC    91.4％

3588    3588    UCAUGGCAGCAUUCACUGG    91.5％   8344    3592    UGCUGAGAUuGAAGAUCUC    1.2％

8298    3588    UCAUGGCAGCAUUCAuUGG    0.2％    8345    3592    UGCUGAGAUuGAAGAUCUu    0.1％

8299    3588    UCAUGGCAGCAUUCgCUGG    0.1％    8346    3592    cGCUGAGAUCGAAGAUCUC    0.2％

8300    3588    UCAUGGCAGCAUUuACUGG    0.4％    8347    3592    UaCUGAGAUCGAAGAUCUC    0.1％

8301    3588    UCAUGGCAGCgUUCACUGG    0.1％    8348    3592    UGGUGAaAUCGAAGAUCUC    0.9％

8302    3588    UuAUGGCAGCAUUCACUGG    1.6％    8349    3592    UGCUGAGAUaGAAGAUCUC    0.1％

8303    3588    UCAUGGCAGCAUUCACcGG    0.3％    8350    3592    UGCUGAGAUCGAAGAUCUa    0.4％

8304    3588    UCAUGGCAGCuUUCACUGG    0.3％    8351    3592    UGCUGAGuUCGAAGAUCUC    0.5％

8305    3588    UCAUGGCuGCAUUCACUGG    0.3％    8352    3592    cGCUGAGAUuGAAGAUCUC    0.2％

8306    3588    UuAUGGCAGCAUUCAaUGG    0.4％    8353    3592    UGCUGAaAUuGAAGAUCUC    4.1％

8307    3588    UuAUGGCAGCAUUuACaGG    1.7％    8354    3592    UGCUGAGAUuGAAGAcCUu    0.2％

8308    3588    UuAUGGCAGCuUUCAuUGG    0.2％    8355    3592    UGCUGAGuaCGAAGAUCUC    0.1％

8309    3588    UuAUGGCAGCuUUCgCUGG    0.1％    8356    3592    cGCUGAaAUuGAAGAUCUC    0.3％

8310    3588    UCAUGGCgGCcUUCACaGG    0.2％    3593    3593    CAGACAUGAGGGCAGAAAU    91.4％

8311    3588    UCAUuGCAGCAUUuACaGG    0.1％    8357    3593    CAGACAUGAGGGCAGAgAU    0.2％

3589    3589    AAUGGUGCUCUCUGCUUUU    91.5％   8358    3593    CAGACAUGAGGGCgGAAAU    0.1％

8312    3589    AAUGGUGCUuUCUGCUUUU    0.2％    8359    3593    CAGAuAUGAGGGCAGAAAU    0.4％

8313    3589    gAUGGUGCUCUCUGCUUUU    1.8％    8360    3593    CgGACAUGAGGGCAGAAAU    0.4％

8314    3589    AAUGGUaCUCUCUGCUUUU    0.8％    8361    3593    CAGACAUGAGaGCAGAAAU    1.4％

8315    3589    AAUGGUGCUaUCUGCUUUU    0.1％    8362    3593    CAGACAUGAGGGCuGAAAU    0.4％

8316    3589    AAUGGUGCUCUCaGCUUUU    0.1％    8363    3593    CuGACAUGAGGGCAGAAAU    0.3％

8317    3589    AAUGGUGCUCUCUGCcUUU    1.1％    3594    3594    AACCCAGGAAAUGCUGAGA    91.4％

8318    3589    AAUGGUGCUCUCUGCgUUU    0.1％    8364    3594    AACCCAGGgAAUGCUGAGA    0.6％

8319    3589    AAUGGUGCUCUCUGCUUUc    0.2％    8365    3594    AAuCCAGGAAAUGCUGAGA    1.0％

8320    3589    AAUGGUaCUCUCUGCaUUU    1.7％    8366    3594    AACCCAaGAAAUGCUGAGA    0.1％

8321    3589    AAUGGUcCUCUcUGCaUUU    0.2％    8367    3594    AACCCAGGAAAcGCUGAGA    0.4％

8322    3589    AAUGGUuCUCUCUGCaUUU    1.9％    8368    3594    AACCCAGGAAAUaCUGAGA    0.1％

3590    3590    ACCCAGGAAUUGCUGAGAU    91.4％   8369    3594    AACCCAGGAAAUGCUGAaA    1.0％

8370    3594    AACCCAGGAAAUGCUGAGu    0.1％    3598    3598    CCAGGAAAUGCCGAGACCG    91.1％

8371    3594    AACCCAGGAAAUGCUGAag    0.1％    8418    3598    CCAGGAAAUGCUGAGAUuG    1.2％

8372    3594    AACCCAGGgAAUGCUGAGu    0.4％    8419    3598    CCAGGgAAUGCUGAGAUCG    0.6％

8373    3594    AAuCCAGGAAAUGCUGAaA    0.1％    8420    3598    CCAaGAAAUGCUGAGAUCG    0.1％

8374    3594    AAuCCAGGAAAUGCUGAGu    0.1％    8421    3598    CCAGGAAAcGCUGAGAUCG    0.2％

8375    3594    AAuCCAGGgAAUGCUGAaA    0.1％    8422    3598    CCAGGAAAUaCUGAGAUCG    0.1％

8376    3594    AAuCCuGGgAAUGCUGAGA    0.3％    8423    3598    CCAGGAAAUGCUGAaAUCG    0.9％

8377    3594    AACCCAGGAAAcGCUGAaA    0.5％    8424    3598    CCAGGAAAUGCUGAGAUaG    0.1％

3595    3595    AAAUGCUGAGAUCGAAGAU    91.2％   8425    3598    CCAGGAAAUGCUGAGuUCG    0.1％

8378    3595    AAAUGCUGAGAUuGAAGAU    1.2％    8426    3598    CCAGGAAAcGCUGAGAUuG    0.2％

8379    3595    gAAUGCUGAGAUCGAAGAU    0.6％    8427    3598    CCAGGAAAUGCUGAaAUuG    0.2％

8380    3595    gAAUGCUGAGAUuGAAGAU    0.1％    8428    3598    CCAGGgAAUGCUGAGuUCG    0.4％

8381    3595    AAAcGCUGAGAUCGAAGAU    0.2％    8429    3598    CCAGGgAAUGCUGAaAUuG    0.1％

8382    3595    AAAUaCUGAGAUCGAAGAU    0.1％    8430    3598    CCuGGgAAUGCUGAGAUuG    0.3％

8383    3595    AAAUGCUGAaAUCGAAGAU    0.9％    8431    3598    CCAGGAAAUGCUGAGuaCG    0.1％

8384    3595    AAAUGCUGAGAUaGAAGAU    0.1％    8432    3598    CCAGGAAAcGCUGAaAUuG    0.5％

8385    3595    AAAUGCUGAGuUCGAAGAU    0.1％    3599    3599    AGGAAAUGCUGAGAUCGAA    91.1％

8386    3595    AAAcGCUGAGAUuGAAGAU    0.2％    8433    3599    AGGAAAUGCUGAGAUuGAA    1.2％

8387    3595    AAAUGCUGAaAUuGAAGAU    0.2％    8434    3599    AGGgAAUGCUGAGAUCGAA    0.6％

8388    3595    gAAUGCUGAGuUCGAAGAU    0.4％    8435    3599    AaGAAAUGCUGAGAUCGAA    0.1％

8389    3595    gAAUGCUGAaAUuGAAGAU    3.9％    8436    3599    AGGAAAcGCUGAGAUCGAA    0.2％

8390    3595    gAAUGCUGAGAUuGAAGAc    0.2％    8437    3599    AGGAAAUaCUGAGAUCGAA    0.1％

8391    3595    AAAUGCUGAGuaCGAAGAU    0.1％    8438    3599    AGGAAAUGCUGAaAUCGAA    0.9％

8392    3595    AAAcGCUGAaAUuGAAGAU    0.5％    8439    3599    AGGAAAUGCUGAGAUaGAA    0.1％

3596    3596    GAAAUGCUGAGAUCGAAGA    91.2％   8440    3599    AGGAAAUGCUGAGuUCGAA    0.1％

8393    3596    GAAAUGCUGAGAUuGAAGA    1.2％    8441    3599    AGGAAAcGCUGAGAUuGAA    0.2％

8394    3596    GgAAUGCUGAGAUCGAAGA    0.6％    8442    3599    AGGAAAUGCUGAaAUuGAA    0.2％

8395    3596    GgAAUGCUGAGAUuGAAGA    0.3％    8443    3599    AGGgAAUGCUGAGuUCGAA    0.4％

8396    3596    GAAAcGCUGAGAUCGAAGA    0.2％    8444    3599    AGGgAAUGCUGAaAUuGAA    0.1％

8397    3596    GAAAUaCUGAGAUCGAAGA    0.1％    8445    3599    uGGgAAUGCUGAGAUuGAA    0.3％

8398    3596    GAAAUGCUGAaAUCGAAGA    0.9％    8446    3599    AGGAAAUGCUGAGuaCGAA    0.1％

8399    3596    GAAAUGCUGAGAUaGAAGA    0.1％    8447    3599    AGGAAAcGCUGAaAUuGAA    0.5％

8400    3596    GAAAUGCUGAGuUCGAAGA    0.1％    3600    3600    CAGGAAAUGCUGAGAUCGA    91.1％

8401    3596    GAAAcGCUGAGAUuGAAGA    0.2％    8448    3600    CAGGAAAUGCUGAGAUuGA    1.2％

8402    3596    GAAAUGCUGAaAUuGAAGA    0.2％    8449    3600    CAGGgAAUGCUGAGAUCGA    0.6％

8403    3596    GgAAUGCUGAGuUCGAAGA    0.4％    8450    3600    CAaGAAAUGCUGAGAUCGA    0.1％

8404    3596    GgAAUGCUGAaAUuGAAGA    3.9％    8451    3600    CAGGAAAcGCUGAGAUCGA    0.2％

8405    3596    GAAAUGCUGAGuaCGAAGA    0.1％    8452    3600    CAGGAAAUaCUGAGAUCGA    0.1％

8406    3596    GAAAcGCUGAaAUuGAAGA    0.5％    8453    3600    CAGGAAAUGCUGAaAUCGA    0.9％

3597    3597    GAACCCAGGAAAUGCUGAG    91.2％   8454    3600    CAGGAAAUGCUGAGAUaGA    0.1％

8407    3597    GAACCCAGGgAAUGCUGAG    0.6％    8455    3600    CAGGAAAUGCUGAGuUCGA    0.1％

8408    3597    GAAuCCAGGAAAUGCUGAG    1.1％    8456    3600    CAGGAAAcGCUGAGAUuGA    0.2％

8409    3597    aAACCCAGGAAAUGCUGAG    0.3％    8457    3600    CAGGAAAUGCUGAaAUuGA    0.2％

8410    3597    GAACCCAaGAAAUGCUGAG    0.1％    8458    3600    CAGGgAAUGCUGAGuUCGA    0.4％

8411    3597    GAACCCAGGAAAcGCUGAG    0.4％    8459    3600    CAGGgAAUGCUGAaAUuGA    0.1％

8412    3597    GAACCCAGGAAAUaCUGAG    0.1％    8460    3600    CuGGgAAUGCUGAGAUuGA    0.3％

8413    3597    GAACCCAGGAAAUGCUGAa    1.0％    8461    3600    CAGGAAAUGCUGAGuaCGA    0.1％

8414    3597    aAACCCAGGgAAUGCUGAG    0.4％    8462    3600    CAGGAAAcGCUGAaAUuGA    0.5％

8415    3597    GAAuCCAGGAAAUGCUGAa    0.1％    3601    3601    GGAAAUGCUGAGAUCGAAG    91.1％

8416    3597    aAACCCAGGAAAUGCUGAa    0.1％    8463    3601    GGAAAUGCUGAGAUuGAAG    1.2％

8417    3597    GAACCCAGGAAAcGCUGAa    0.5％    8464    3601    GGgAAUGCUGAGAUCGAAG    0.6％

8465    3601    GGgAAUGCUGAGAUuGAAG    0.3％    8512    3605    GgAAAUUUCAAgCAGCUGC    0.1％

8466    3601    aGAAAUGCUGAGAUCGAAG    0.1％    8513    3605    GgAAAUUUCAgACAGCUGC    0.3％

8467    3601    GGAAAcGCUGAGAUCGAAG    0.2％    8514    3605    GAAAAcUUCAAACAGCUGC    0.2％

8468    3601    GGAAAUaCUGAGAUCGAAG    0.1％    8515    3605    GAAAAUUcCAAACAGCUGC    0.1％

8469    3601    GGAAAUGCUGAaAUCGAAG    0.9％    8516    3605    GAAAAUUUCAAACuGCUGC    0.1％

8470    3601    GGAAAUGCUGAGAUaGAAG    0.1％    8517    3605    GuAAAUUUCAAACAGCUGC    0.1％

8471    3601    GGAAAUGCUGAGuUCGAAG    0.1％    8518    3605    GgAAAUUUCAAACAGCaGC    2.1％

8472    3601    GGAAAcGCUGAGAUuGAAG    0.2％    8519    3605    GgAAAUUUCAAACuGCUGC    0.4％

8473    3601    GGAAAUGCUGAaAUuGAAG    0.2％    8520    3605    GgAAAUUUCAAACgGCaGC    0.1％

8474    3601    GGgAAUGCUGAGuUCGAAG    0.4％    8521    3605    GgAAAUUcCAAACAGCaGC    1.9％

8475    3601    GGgAAUGCUGAaAUuGAAG    3.9％    3606    3606    GGAAAAUUUCAAACAGCUG    90.1％

8476    3601    GGAAAUGCUGAGuaCGAAG    0.1％    8522    3606    GGAAAAUUUCAAACgGCUG    0.4％

8477    3601    GGAAAcGCUGAaAUuGAAG    0.5％    8523    3606    GGAAAAUUUCAgACAGCUG    0.3％

3602    3602    UGGAUCAAGUGAGAGAAAG    90.7％   8524    3606    GGgAAAUUUCAAACAGCUG    3.7％

8478    3602    UGGAUCAAGUGAGAGAgAG    0.6％    8525    3606    GGAAAgUUUCAgACAGCUG    0.1％

8479    3602    UGGAUCAAGUGAGgGAAAG    0.1％    8526    3606    GGgAAAUUUCAAgCAGCUG    0.1％

8480    3602    UGGAUCAgGUGAGAGAAAG    0.2％    8527    3606    GGgAAAUUUCAgACAGCUG    0.3％

8481    3602    UaGAUCAAGUGAGAGAAAG    0.1％    8528    3606    GGAAAAcUUCAAACAGCUG    0.2％

8482    3602    UGGAcCAAGUGAGAGAAAG    2.6％    8529    3606    GGAAAAUUcCAAACAGCUG    0.1％

8483    3602    UGGAUCAAGUaAGAGAAAG    1.5％    8530    3606    GGAAAAUUUCAAACuGCUG    0.1％

8484    3602    UGGAUCcAGUGAGAGAAAG    0.1％    8531    3606    GGuAAAUUUCAAACAGCUG    0.1％

8485    3602    UGGAUCAAGUGcGAGAgAG    1.6％    8532    3606    GGgAAAUUUCAAACAGCaG    2.1％

8486    3602    UGGAUCAgGUGcGAGAAAG    2.1％    8533    3606    GGgAAAUUUCAAACuGCUG    0.4％

8487    3602    UGGAcCAgGUGAGgGAAAG    0.1％    8534    3606    GGgAAAUUUCAAACgGCaG    0.1％

8488    3602    UGGAcCAAGUGcGAGAgAG    0.1％    8535    3606    GGgAAAUUcCAAACAGCaG    1.9％

8489    3602    UGGAcCAgGUGcGAGAAAG    0.1％    3607    3607    AAAGGAAAAUUUCAAACAG    90.0％

3603    3603    UAUGAGAGAAUGUGCAACA    90.4％   8536    3607    AAAGGAAAAUUUCAAACgG    0.4％

8490    3603    UAUGAGAGAAUGUGCAACg    0.1％    8537    3607    AAAGGAAAAUUUCAgACAG    0.3％

8491    3603    UAUGAGAGAAUGUGCAAuA    0.5％    8538    3607    AAAGGgAAAUUUCAAACAG    5.8％

8492    3603    UAUGAGAGgAUGUGCAACA    0.4％    8539    3607    AAgGGAAAAUUUCAAACAG    0.1％

8493    3603    UAcGAGAGAAUGUGCAACA    6.6％    8540    3607    AAAGGAAAgUUUCAgACAG    0.1％

8494    3603    UAUGAaAGAAUGUGCAACA    1.1％    8541    3607    AAAGGgAAAUUUCAAACgG    0.1％

8495    3603    UAUGAuAGAAUGUGCAACA    0.3％    8542    3607    AAAGGgAAAUUUCAAgCAG    0.1％

8496    3603    UAcGAGAGgAUGUGCAACA    0.2％    8543    3607    AAAGGgAAAUUUCAgACAG    0.3％

8497    3603    UAUGAaAGAAUGUGCAAuA    0.4％    8544    3607    AAAGGAAAAcUUCAAACAG    0.2％

8498    3603    UAcGAaAGAAUGUGCAACA    0.1％    8545    3607    AAAGGAAAAUUcCAAACAG    0.1％

3604    3604    AUGAGAGAAUGUGCAACAU    90.4％   8546    3607    AAAGGAAAAUUUCAAACuG    0.1％

8499    3604    AUGAGAGAAUGUGCAACgU    0.1％    8547    3607    AAAGGuAAAUUUCAAACAG    0.1％

8500    3604    AUGAGAGAAUGUGCAAuAU    0.5％    8548    3607    AAAGGgAAAUUcCAAACAG    1.9％

8501    3604    AUGAGAGgAUGUGCAACAU    0.4％    8549    3607    AAAGGgAAAUUUCAAACuG    0.4％

8502    3604    AcGAGAGAAUGUGCAACAU    6.6％    8550    3607    AAAGGgAAAUUUCAgACcG    0.1％

8503    3604    AUGAaAGAAUGUGCAACAU    1.1％    3608    3608    AGGAAAAUUUCAAACAGCU    90.0％

8504    3604    AUGAuAGAAUGUGCAACAU    0.3％    8551    3608    AGGAAAAUUUCAAACgGCU    0.4％

8505    3604    AcGAGAGgAUGUGCAACAU    0.2％    8552    3608    AGGAAAAUUUCAgACAGCU    0.3％

8506    3604    AUGAaAGAAUGUGCAAuAU    0.4％    8553    3608    AGGgAAAUUUCAAACAGCU    3.7％

8507    3604    AcGAaAGAAUGUGCAACAU    0.1％    8554    3608    gGGAAAAUUUCAAACAGCU    0.1％

3605    3605    GAAAAUUUCAAACAGCUGC    90.1％   8555    3608    AGGAAAgUUUCAgACAGCU    0.1％

8508    3605    GAAAAUUUCAAACgGCUGC    0.4％    8556    3608    AGGgAAAUUUCAAgCAGCU    0.1％

8509    3605    GAAAAUUUCAgACAGCUGC    0.3％    8557    3608    AGGgAAAUUUCAgACAGCU    0.3％

8510    3605    GgAAAUUUCAAACAGCUGC    3.7％    8558    3608    AGGAAAAcUUCAAACAGCU    0.2％

8511    3605    GAAAgUUUCAgACAGCUGC    0.1％    8559    3608    AGGAAAAUUcCAAACAGCU    0.1％

8560  3608    AGGAAAAUUUCAAACuGCU    0.1％    8578  3609    AAGGgAAAUUcCAAACAGC    1.9％

8561  3608    AGGUAAAUUUCAAACAGCU    0.1％    8579  3609    AAGGgAAAUUUCAAACuGC    0.4％

8562  3608    AGGgAAAUUUCAAACAGCa    2.1％    8580  3609    AAGGgAAAUUUCAgACcGC    0.1％

8563  3608    AGGgAAAUUUCAAACuGCU    0.4％    3610  3610    CCCAGGAAAUGCUGAGAUC    90.0％

8564  3608    AGGgAAAUUUCAAACgGCa    0.1％    8581  3610    CCCAGGAAAUGCUGAGAUu    1.2％

8565  3608    AGGgAAAUUc AAACAGCa    1.9％    8582  3610    CCCAGGgAAUGCUGAGAUC    0.6％

3609  3609    AAGGAAAAUUUCAAACAGC    90.0％   8583  3610    uCCAGGAAAUGCUGAGAUC    1.0％

8566  3609    AAGGAAAAUUUCAAACgGC    0.4％    8584  3610    CCCAaGAAAUGCUGAGAUC    0.1％

8567  3609    AAGGAAAAUUUCAgACAGC    0.3％    8585  3610    CCCAGGAAAcGCUGAGAUC    0.2％

8568  3609    AAGGgAAAUUUCAAACAGC    5.8％    8586  3610    CCCAGGAAAUaCUGAGAUC    0.1％

8569  3609    AgGGAAAAUUUCAAACAGC    0.1％    8587  3610    CCCAGGAAAUGCUGAaAUC    0.9％

8570  3609    AAGGAAAgUUUCAgACAGC    0.1％    8588  3610    CCCAGGAAAUGCUGAGAUa    0.1％

8571  3609    AAGGgAAAUUUCAAACgGC    0.1％    8589  3610    CCCAGGAAAcGCUGAGAUu    0.2％

8572  3609    AAGGgAAAUUUCAAgCAGC    0.1％    8590  3610    CCCAGGAAAUGCUGAaAUu    0.1％

8573  3609    AAGGgAAAUUUCAgACAGC    0.3％    8591  3610    CCCAGGgAAUGCUGAGuUC    0.4％

8574  3609    AAGGAAAAcUUCAAACAGC    0.2％    8592  3610    uCCAGGAAAUGCUGAGuUC    0.1％

8575  3609    AAGGAAAAUUcCAAACAGC    0.1％    8593  3610    uCCAGGAAAUGCUGAaAUu    0.1％

8576  3609    AAGGAAAAUUUCAAACuGC    0.1％    8594  3610    CCCAGGAAAUGCUGAGuaC    0.1％

8577  3609    AAGGuAAAUUUCAAACAGC    0.1％    8595  3610    CCCAGGAAAcGCUGAaAUu    0.5％

表20-5.从表1-7所列甲型流感片段7(M1&M2)序列得到的保守和小变体19-mer序列。保守序列匹配所列病毒序列的至少89％，变体含有从参考序列的3个或更少核苷酸变化。

SeQ ID RefID    匹配序列               ％总数    8619    4432    CGCUCACCGUGCCuAGUGA    0.1％

4427    4427    UUCACGCUCACCGUGCCCA    99.2％    8620    4432    CGCUCACuGUGCCCAGUGA    0.2％

8596    4427    UUCACGCUCACCGUGCCuA    0.1％     8621    4432    CaCUCACCGUGCCCAGUGA    0.2％

8597    4427    UUCACGCUCACuGUGCCCA    0.2％     8622    4432    CGCUCACCGUGCCaAGUGA    0.2％

8598    4427    UUCACaCUCACCGUGCCCA    0.2％     8623    4432    CGCUCACCGUGCCCAcUGA    0.3％

8599    4427    UUCACGCUCACCGUGCCaA    0.2％     8624    4432    CGCUCACCGUGCCCAGcGA    0.1％

4428    4428    CAGGCCCCCUCAAAGCCGA    99.0％    8625    4432    CGCUCACCGUGCCCAGUaA    0.1％

8600    4428    CgGGCCCCCUCAAAGCCGA    0.2％     4433    4433    ACGCUCACCGUGCCCAGUG    98.8％

8601    4428    uAGGCCCCCUCAAAGCCGA    0.1％     8626    4433    ACGCUCACCGUGCCuAGUG    0.1％

8602    4428    CAGGCCCCCUCAAAGCCcA    0.5％     8627    4433    ACGCUCACuGUGCCCAGUG    0.2％

8603    4428    CcGGCCCCCUCAAAGCCGA    0.2％     8628    4433    ACaCUCACCGUGCCCAGUG    0.2％

4429    4429    UCAGGCCCCCUCAAAGCCG    99.0％    8629    4433    ACGCUCACCGUGCCaAGUG    0.2％

8604    4429    UCgGGCCCCCUCAAAGCCG    0.2％     8630    4433    ACGCUCACCGUGCCCAcUG    0.3％

8605    4429    UuAGGCCCCCUCAAAGCCG    0.1％     8631    4433    ACGCUCACCGUGCCCAGcG    0.1％

8606    4429    UCAGGCCCCCUCAAAGCCc    0.5％     8632    4433    ACGCUCACCGUGCCCAGUa    0.1％

8607    4429    UCcGGCCCCCUCAAAGCCG    0.2％     4434    4434    UCACCGUGCCCAGUGAGCG    98.7％

4430    4430    UCACGCUCACCGUGCCCAG    98.9％    8633    4434    UCACCGUGCCuAGUGAGCG    0.1％

8608    4430    UCACGCUCACCGUGCCuAG    0.1％     8634    4434    UCACuGUGCCCAGUGAGCG    0.2％

8609    4430    UCACGCUCACuGUGCCCAG    0.2％     8635    4434    UCACCGUGCCaAGUGAGCG    0.2％

8610    4430    UCACaCUCACCGUGCCCAG    0.2％     8636    4434    UCACCGUGCCCAcUGAGCG    0.3％

8611    4430    UCACGCUCACCGUGCCaAG    0.2％     8637    4434    UCACCGUGCCCAGcGAGCG    0.1％

8612    4430    UCACGCUCACCGUGCCCAc    0.3％     8638    4434    UCACCGUGCCCAGUaAGCG    0.1％

4431    4431    CACGCUCACCGUGCCCAGU    98.8％    8639    4434    UCACCGUGCCCAGUGAaCG    0.3％

8613    4431    CACGCUCACCGUGCCuAGU    0.1％     4435    4435    CUCACCGUGCCCAGUGAGC    98.7％

8614    4431    CACGCUCACuGUGCCCAGU    0.2％     8640    4435    CUCACCGUGCCuAGUGAGC    0.1％

8615    4431    CACaCUCACCGUGCCCAGU    0.2％     8641    4435    CUCACuGUGCCCAGUGAGC    0.2％

8616    4431    CACGCUCACCGUGCCaAGU    0.2％     8642    4435    CUCACCGUGCCaAGUGAGC    0.2％

8617    4431    CACGCUCACCGUGCCCAcU    0.3％     8643    4435    CUCACCGUGCCCAcUGAGC    0.3％

8618    4431    CACGCUCACCGUGCCCAGc    0.1％     8644    4435    CUCACCGUGCCCAGcGAGC    0.1％

4432    4432    CGCUCACCGUGCCCAGUGA    98.8％    8645    4435    CUCACCGUGCCCAGUaAGC    0.1％

8646    4435    CUCACCGUGCCCAGUGAaC    0.3％    8695    4442    GGACUGCAGCGUAGACGuU    0.2％

4436    4436    GCUCACCGUGCCCAGUGAG    98.5％   8696    4442    GGACUGCAaCGUAGACGCU    1.7％

8647    4436    GCUCACCGUGCCuAGUGAG    0.1％    8697    4442    GGACUGCAGCGUAaACGCU    0.1％

8648    4436    GCUCACuGUGCCCAGUGAG    0.2％    8698    4442    GGACUGCAGCGUAcACGCU    0.1％

8649    4436    aCUCACCGUGCCCAGUGAG    0.2％    8699    4442    GGACUGCAGCGUAGACGaU    1.5％

8650    4436    GCUCACCGUGCCaAGUGAG    0.2％    8700    4442    GGACUGCAGCGUAGACGgU    0.3％

8651    4436    GCUCACCGUGCCCAcUGAG    0.3％    8701    4442    GGACUGCAGCGUAuACGCU    0.2％

8652    4436    GCUCACCGUGCCCAGcGAG    0.1％    8702    4442    GGACUGCAaCGUAuACGCU    0.1％

8653    4436    GCUCACCGUGCCCAGUaAG    0.1％    8703    4442    GGACUGCAGCGUAuACGaU    0.1％

8654    4436    GCUCACCGUGCCCAGUGAa    0.3％    4443    4443    UGCAGCGUAGACGCUUUGU    95.5％

4437    4437    AUCUUGAGGCUCUCAUGGA    96.4％   8704    4443    UGCAGCGUAGACGuUUUGU    0.2％

8655    4437    AUCUUGAGGuUCUCAUGGA    0.9％    8705    4443    UGCAaCGUAGACGCUUUGU    1.7％

8656    4437    AcCUUGAGGCUCUCAUGGA    0.3％    8706    4443    UGCAGCGUAaACGCUUUGU    0.1％

8657    4437    AUCUaGAGGCUCUCAUGGA    0.1％    8707    4443    UGCAGCGUAcACGCUUUGU    0.1％

8658    4437    AUCUcGAGGCUCUCAUGGA    1.6％    8708    4443    UGCAGCGUAGACGaUUUGU    1.5％

8659    4437    AUCUUGAaGCUCUCAUGGA    0.1％    8709    4443    UGCAGCGUAGACGCUUcGU    0.1％

8660    4437    AUCUUGAGGCaCUCAUGGA    0.3％    8710    4443    UGCAGCGUAGACGgUUUGU    0.3％

8661    4437    AUCUUGAGGCUCUaAUGGA    0.1％    8711    4443    UGCAGCGUAuACGCUUUGU    0.2％

8662    4437    AUCUUGAGGCUCUCAcGGA    0.1％    8712    4443    UGCAaCGUAuACGCUUUGU    0.1％

8663    4437    AUCUUGAGGuUCUCAcGGA    0.1％    8713    4443    UGCAGCGUAuACGaUUUGU    0.1％

4438    4438    GAUCUUGAGGCUCUCAUGG    96.4％   4444    4444    ACUGCAGCGUAGACGCUUU    95.5％

8664    4438    GAUCUUGAGGuUCUCAUGG    0.9％    8714    4444    ACUGCAGCGUAGACGuUUU    0.2％

8665    4438    GAcCUUGAGGCUCUCAUGG    0.3％    8715    4444    ACUGCAaCGUAGACGCUUU    1.7％

8666    4438    GAUCUaGAGGCUCUCAUGG    0.1％    8716    4444    ACUGCAGCGUAaACGCUUU    0.1％

8667    4438    GAUCUcGAGGCUCUCAUGG    1.6％    8717    4444    ACUGCAGCGUAcACGCUUU    0.1％

8668    4438    GAUCUUGAaGCUCUCAUGG    0.1％    8718    4444    ACUGCAGCGUAGACGaUUU    1.5％

8669    4438    GAUCUUGAGGCaCUCAUGG    0.3％    8719    4444    ACUGCAGCGUAGACGCUUc    0.1％

8670    4438    GAUCUUGAGGCUCUaAUGG    0.1％    8720    4444    ACUGCAGCGUAGACGgUUU    0.3％

8671    4438    GAUCUUGAGGCUCUCAcGG    0.1％    8721    4444    ACUGCAGCGUAuACGCUUU    0.2％

8672    4438    GAUCUUGAGGuUCUCAcGG    0.1％    8722    4444    ACUGCAaCGUAuACGCUUU    0.1％

4439    4439    UGUCACCUCUGACUAAGGG    96.3％   8723    4444    ACUGCAGCGUAuACGaUUU    0.1％

8673    4439    UGUCACCUCUGACUAgGGG    0.1％    4445    4445    CUGCAGCGUAGACGCUUUG    95.5％

8674    4439    UGUCACCUCUaACUAAGGG    0.9％    8724    4445    CUGCAGCGUAGACGuUUUG    0.2％

8675    4439    UGUCACCUCUGACaAAGGG    0.4％    8725    4445    CUGCAaCGUAGACGCUUUG    1.7％

8676    4439    UGUCACCUCUGACcAAGGG    0.3％    8726    4445    CUGCAGCGUAaACGCUUUG    0.1％

8677    4439    UGUCACCUCUGACUAAaGG    2.0％    8727    4445    CUGCAGCGUAcACGCUUUG    0.1％

8678    4439    UGUCACCUCUuACUAAGGG    0.1％    8728    4445    CUGCAGCGUAGACGaUUUG    1.5％

4440    4440    CUGUCACCUCUGACUAAGG    96.3％   8729    4445    CUGCAGCGUAGACGCUUcG    0.1％

8679    4440    CUGUCACCUCUGACUAgGG    0.1％    8730    4445    CUGCAGCGUAGACGgUUUG    0.3％

8680    4440    CUGUCACCUCUaACUAAGG    0.9％    8731    4445    CUGCAGCGUAuACGCUUUG    0.2％

8681    4440    CUGUCACCUCUGACaAAGG    0.4％    8732    4445    CUGCAaCGUAuACGCUUUG    0.1％

8682    4440    CUGUCACCUCUGACcAAGG    0.3％    8733    4445    CUGCAGCGUAuACGaUUUG    0.1％

8683    4440    CUGUCACCUCUGACUAAaG    1.9％    4446    4446    GCUAUGGAGCAAAUGGCUG    95.4％

8684    4440    CUGUCACCUCUuACUAAGG    0.1％    8734    4446    GCcAUGGAGCAAAUGGCUG    0.4％

8685    4440    uUGUCACCUCUGACUAAaG    0.1％    8735    4446    GCUAUGGAaCAAAUGGCUG    0.4％

4441    4441    GACUGCAGCGUAGACGCUU    95.6％   8736    4446    GCUAUGGAGCAcAUGGCUG    0.1％

8686    4441    GACUGCAGCGUAGACGuUU    0.2％    8737    4446    GCcAUGGAGCAgAUGGCUG    1.5％

8687    4441    GACUGCAaCGUAGACGCUU    1.7％    8738    4446    GCUAUGGAGCAgAUGGCaG    0.3％

8688    4441    GACUGCAGCGUAaACGCUU    0.1％    8739    4446    GCUAUGGAGCAgAUGGCgG    1.3％

8689    4441    GACUGCAGCGUAcACGCUU    0.1％    8740    4446    GCUAUGGAaCAgAUGGuUG    0.1％

8690    4441    GACUGCAGCGUAGACGaUU    1.5％    8741    4446    GCcAUGGAaCAAAUGGCUG    0.4％

8691    4441    GACUGCAGCGUAGACGgUU    0.3％    8742    4446    GCcAUGGAGCAgAUGGCaG    0.1％

8692    4441    GACUGCAGCGUAuACGCUU    0.2％    4447    4447    UGGCUAAAGACAAGACCAA    95.4％

8693    4441    GACUGCAaCGUAuACGCUU    0.1％    8743    4447    UGGCUAAAGACAAGACCgA    3.5％

8694    4441    GACUGCAGCGUAuACGaUU    0.1％    8744    4447    UGGCUAAAGACAAGgCCAA    0.4％

4442    4442    GGACUGCAGCGUAGACGCU    95.6％   8745    4447    UGGCUgAAGACAAGACCAA    0.1％

8746    4447    UGGuUAAAGACAAGACCgA    0.1％    8797    4452    GGCUAAAGACAAGgCCAAU    0.4％

8747    4447    UGGCUAAAGACAAaACCAA    0.2％    8798    4452    GGCUgAAGACAAGACCAAU    0.1％

8748    4447    UGGCUAAAGACAAGACCcA    0.1％    8799    4452    GGuUAAAGACAAGACCgAU    0.1％

8749    4447    UGGCUAAAGACAAGACCuA    0.1％    8800    4452    GGCUAAAGACAAaACCAAU    0.2％

8750    4447    UGGCUAAAGACuAGACCuA    0.2％    8801    4452    GGCUAAAGACAAGACCcAU    0.1％

4448    4448    CAGCGUAGACGCUUUGUCC    95.4％   8802    4452    GGCUAAAGACAAGACCuAU    0.1％

8751    4448    CAGCGUAGACGCUUUGUuC    0.1％    8803    4452    GGCUAAAGACuAGACCuAU    0.2％

8752    4448    CAGCGUAGACGuUUUGUCC    0.2％    4453    4453    CGUAGACGCUUUGUCCAAA    94.9％

8753    4448    CAaCGUAGACGCUUUGUCC    1.5％    8804    4453    CGUAGACGCUUUGUCCAgA    2.0％

8754    4448    CAGCGUAaACGCUUUGUCC    0.1％    8805    4453    CGUAGACGCUUUGUuCAAA    0.3％

8755    4448    CAGCGUAcACGCUUUGUCC    0.1％    8806    4453    CGUAGACGuUUUGUCCAAA    0.2％

8756    4448    CAGCGUAGACGaUUUGUCC    1.5％    8807    4453    CGUAcACGCUUUGUCCAAA    0.1％

8757    4448    CAGCGUAGACGCUUcGUCC    0.1％    8808    4453    CGUAGACGaUUUGUCCAAA    1.5％

8758    4448    CAGCGUAGACGgUUUGUCC    0.3％    8809    4453    CGUAGACGCUUcGUCCAAA    0.1％

8759    4448    CAGCGUAuACGCUUUGUCC    0.2％    8810    4453    CGUAGACGgUUUGUCCAAA    0.3％

8760    4448    CAaCGUAGACGCUUUGUuC    0.2％    8811    4453    CGUAuACGCUUUGUCCAAA    0.3％

8761    4448    CAaCGUAuACGCUUUGUCC    0.1％    8812    4453    CGUAaACGCUUUGUCCAgA    0.1％

8762    4448    CAGCGUAuACGaUUUGUCC    0.1％    8813    4453    CGUAcACuCUUUGUCCAAA    0.1％

4449    4449    CUAUGGAGCAAAUGGCUGG    95.4％   8814    4453    CGUAuACGaUUUGUCCAAA    0.1％

8763    4449    CcAUGGAGCAAAUGGCUGG    0.4％    4454    4454    GUAGACGCUUUGUCCAAAA    94.9％

8764    4449    CUAUGGAaCAAAUGGCUGG    0.4％    8815    4454    GUAGACGCUUUGUCCAgAA    2.0％

8765    4449    CUAUGGAGCAcAUGGCUGG    0.1％    8816    4454    GUAGACGCUUUGUuCAAAA    0.3％

8766    4449    CcAUGGAGCAgAUGGCUGG    1.5％    8817    4454    GUAGACGuUUUGUCCAAAA    0.2％

8767    4449    CUAUGGAGCAgAUGGCaGG    0.3％    8818    4454    GUAcACGCUUUGUCCAAAA    0.1％

8768    4449    CUAUGGAGCAgAUGGCgGG    1.3％    8819    4454    GUAGACGaUUUGUCCAAAA    1.5％

8769    4449    CUAUGGAaCAgAUGGuUGG    0.1％    8820    4454    GUAGACGCUUcGUCCAAAA    0.1％

8770    4449    CcAUGGAaCAAAUGGCUGG    0.4％    8821    4454    GUAGACGgUUUGUCCAAAA    0.3％

8771    4449    CcAUGGAGCAgAUGGCaGG    0.1％    8822    4454    GUAuACGCUUUGUCCAAAA    0.3％

4450    4450    AGCGUAGACGCUUUGUCCA    95.4％   8823    4454    GUAaACGCUUUGUCCAgAA    0.1％

8772    4450    AGCGUAGACGCUUUGUuCA    0.1％    8824    4454    GUAcACuCUUUGUCCAAAA    0.1％

8773    4450    AGCGUAGACGuUUUGUCCA    0.2％    8825    4454    GUAuACGaUUUGUCCAAAA    0.1％

8774    4450    AaCGUAGACGCUUUGUCCA    1.5％    4455    4455    AGACGCUUUGUCCAAAAUG    94.8％

8775    4450    AGCGUAaACGCUUUGUCCA    0.1％    8826    4455    AGACGCUUUGUCCAgAAUG    1.3％

8776    4450    AGCGUAcACGCUUUGUCCA    0.1％    8827    4455    AGACGCUUUGUuCAAAAUG    0.3％

8777    4450    AGCGUAGACGaUUUGUCCA    1.5％    8828    4455    AGACGuUUUGUCCAAAAUG    0.2％

8778    4450    AGCGUAGACGCUUcGUCCA    0.1％    8829    4455    AcACGCUUUGUCCAAAAUG    0.1％

8779    4450    AGCGUAGACGgUUUGUCCA    0.3％    8830    4455    AGACGaUUUGUCCAAAAUG    1.5％

8780    4450    AGCGUAuACGCUUUGUCCA    0.2％    8831    4455    AGACGCUUcGUCCAAAAUG    0.1％

8781    4450    AaCGUAGACGCUUUGUuCA    0.2％    8832    4455    AGACGCUUUGUCCAAAAcG    0.1％

8782    4450    AaCGUAuACGCUUUGUCCA    0.1％    8833    4455    AGACGgUUUGUCCAAAAUG    0.3％

8783    4450    AGCGUAuACGaUUUGUCCA    0.1％    8834    4455    AuACGCUUUGUCCAAAAUG    0.3％

4451    4451    GCAGCGUAGACGCUUUGUC    95.4％   8835    4455    AaACGCUUUGUCCAgAAUG    0.1％

8784    4451    GCAGCGUAGACGCUUUGUu    0.1％    8836    4455    AGACGCUUUGUCCAgAAcG    0.7％

8785    4451    GCAGCGUAGACGuUUUGUC    0.2％    8837    4455    AcACuCUUUGUCCAAAAUG    0.1％

8786    4451    GCAaCGUAGACGCUUUGUC    1.5％    8838    4455    AuACGaUUUGUCCAAAAUG    0.1％

8787    4451    GCAGCGUAaACGCUUUGUC    0.1％    4456    4456    UAGACGCUUUGUCCAAAAU    94.8％

8788    4451    GCAGCGUAcACGCUUUGUC    0.1％    8839    4456    UAGACGCUUUGUCCAgAAU    1.3％

8789    4451    GCAGCGUAGACGaUUUGUC    1.5％    8840    4456    UAGACGCUUUGUuCAAAAU    0.3％

8790    4451    GCAGCGUAGACGCUUcGUC    0.1％    8841    4456    UAGACGuUUUGUCCAAAAU    0.2％

8791    4451    GCAGCGUAGACGgUUUGUC    0.3％    8842    4456    UAcACGCUUUGUCCAAAAU    0.1％

8792    4451    GCAGCGUAuACGCUUUGUC    0.2％    8843    4456    UAGACGaUUUGUCCAAAAU    1.5％

8793    4451    GCAaCGUAGACGCUUUGUu    0.2％    8844    4456    UAGACGCUUcGUCCAAAAU    0.1％

8794    4451    GCAaCGUAuACGCUUUGUC    0.1％    8845    4456    UAGACGCUUUGUCCAAAAc    0.1％

8795    4451    GCAGCGUAuACGaUUUGUC    0.1％    8846    4456    UAGACGgUUUGUCCAAAAU    0.3％

4452    4452    GGCUAAAGACAAGACCAAU    95.4％   8847    4456    UAuACGCUUUGUCCAAAAU    0.3％

8796    4452    GGCUAAAGACAAGACCgAU    3.5％    8848    4456    UAaACGCUUUGUCCAgAAU    0.1％

8849    4456    UAGACGCUUUGUCCAgAAc    0.7％    8901    4460    CGCUUUGUCCAgAAcGCCC    0.7％

8850    4456    UAcACuCUUUGUCCAAAAU    0.1％    4461    4461    UCAGUUAUUCUGCUGGUGC    94.2％

8851    4456    UAuACGaUUUGUCCAAAAU    0.1％    8902    4461    UCgGUUAUUCUGCUGGUGC    0.1％

4457    4457    GACGCUUUGUCCAAAAUGC    94.7％   8903    4461    UuAGUUAUUCUGCUGGUGC    0.5％

8852    4457    GACGCUUUGUCCAAAAUGu    0.1％    8904    4461    UCAGcUAUUCUGCUGGUGC    0.2％

8853    4457    GACGCUUUGUCCAgAAUGC    1.3％    8905    4461    UCAGUUAcUCUGCUGGUGC    1.0％

8854    4457    GACGCUUUGUuCAAAAUGC    0.3％    8906    4461    UCAGUUAUUCcGCUGGUGC    0.1％

8855    4457    GACGuUUUGUCCAAAAUGC    0.2％    8907    4461    UCAGUUAUUCgGCUGGUGC    0.1％

8856    4457    cACGCUUUGUCCAAAAUGC    0.1％    8908    4461    UCAGUUAUUCUGCcGGUGC    0.2％

8857    4457    GACGaUUUGUCCAAAAUGC    1.5％    8909    4461    UCAGUUAUUCUGCUGGcGC    0.1％

8858    4457    GACGCUUcGUCCAAAAUGC    0.1％    4462    4462    AUUCUGCUGGUGCACUUGC    94.1％

8859    4457    GACGCUUUGUCCAAAAcGC    0.1％    8910    4462    AUUCUGCUGGUGCgCUUGC    0.9％

8860    4457    GACGgUUUGUCCAAAAUGC    0.3％    8911    4462    AcUCUGCUGGUGCACUUGC    1.0％

8861    4457    uACGCUUUGUCCAAAAUGC    0.3％    8912    4462    AUUCcGCUGGUGCACUUGC    0.1％

8862    4457    aACGCUUUGUCCAgAAUGC    0.1％    8913    4462    AUUCgGCUGGUGCACUUGC    0.1％

8863    4457    GACGCUUUGUCCAgAAcGC    0.7％    8914    4462    AUUCUGCcGGUGCACUUGC    0.2％

8864    4457    cACuCUUUGUCCAAAAUGC    0.1％    8915    4462    AUUCUGCUGGcGCACUUGC    0.1％

8865    4457    uACGaUUUGUCCAAAAUGC    0.1％    4463    4463    CUCAUGGAAUGGCUAAAGA    94.1％

4458    4458    ACGCUUUGUCCAAAAUGCC    94.3％   8916    4463    CUCAUGGAAUGGCUgAAGA    0.1％

8866    4458    ACGCUUUGUCCAAAAUGCu    0.6％    8917    4463    CUCAUGGAAUGGuUAAAGA    0.1％

8867    4458    ACGCUUUGUCCAAAAUGuC    0.1％    8918    4463    CUCAUGGAgUGGCUAAAGA    5.4％

8868    4458    ACGCUUUGUCCAgAAUGCC    1.4％    8919    4463    CUaAUGGAAUGGCUAAAGA    0.1％

8869    4458    ACGCUUUGUuCAAAAUGCC    0.3％    8920    4463    CUCAcGGAAUGGCUAAAGA    0.2％

8870    4458    ACGuUUUGUCCAAAAUGCC    0.2％    4464    4464    UCAUGGAAUGGCUAAAGAC    94.1％

8871    4458    ACGaUUUGUCCAAAAUGCC    1.6％    8921    4464    UCAUGGAAUGGCUgAAGAC    0.1％

8872    4458    ACGCUUcGUCCAAAAUGCC    0.1％    8922    4464    UCAUGGAAUGGuUAAAGAC    0.1％

8873    4458    ACGCUUUGUCCAAAAcGCC    0.1％    8923    4464    UCAUGGAgUGGCUAAAGAC    5.4％

8874    4458    ACGCUUUGUCCAAAAUGCa    0.2％    8924    4464    UaAUGGAAUGGCUAAAGAC    0.1％

8875    4458    ACGgUUUGUCCAAAAUGCC    0.3％    8925    4464    UCAcGGAAUGGCUAAAGAC    0.2％

8876    4458    ACuCUUUGUCCAAAAUGCC    0.1％    4465    4465    UAUUCUGCUGGUGCACUUG    94.1％

8877    4458    ACGCUUUGUCCAgAAcGCC    0.7％    8926    4465    UAUUCUGCUGGUGCgCUUG    0.9％

4459    4459    GCUUUGUCCAAAAUGCCCU    94.3％   8927    4465    UAcUCUGCUGGUGCACUUG    1.0％

8878    4459    GCUUUGUCCAAAAUGCuCU    0.6％    8928    4465    UAUUCcGCUGGUGCACUUG    0.1％

8879    4459    GCUUUGUCCAAAAUGuCCU    0.1％    8929    4465    UAUUCgGCUGGUGCACUUG    0.1％

8880    4459    GCUUUGUCCAgAAUGCCCU    1.4％    8930    4465    UAUUCUGCcGGUGCACUUG    0.2％

8881    4459    GCUUUGUuCAAAAUGCCCU    0.3％    8931    4465    UAUUCUGCUGGcGCACUUG    0.1％

8882    4459    GuUUUGUCCAAAAUGCCCU    0.2％    4466    4466    AUGGAAUGGCUAAAGACAA    94.0％

8883    4459    GaUUUGUCCAAAAUGCCCU    1.6％    8932    4466    AUGGAAUGGCUgAAGACAA    0.1％

8884    4459    GCUUcGUCCAAAAUGCCCU    0.1％    8933    4466    AUGGAAUGGuUAAAGACAA    0.1％

8885    4459    GCUUUGUCCAAAAcGCCCU    0.1％    8934    4466    AUGGAgUGGCUAAAGACAA    5.4％

8886    4459    GCUUUGUCCAAAAUGCaCU    0.2％    8935    4466    AcGGAAUGGCUAAAGACAA    0.2％

8887    4459    GgUUUGUCCAAAAUGCCCU    0.3％    8936    4466    AUGGAAUGGCUAAAGACuA    0.2％

8888    4459    uCUUUGUCCAAAAUGCCCU    0.1％    4467    4467    CUCAGUUAUUCUGCUGGUG    94.0％

8889    4459    GCUUUGUCCAgAAcGCCCU    0.7％    8937    4467    CUCgGUUAUUCUGCUGGUG    0.1％

4460    4460    CGCUUUGUCCAAAAUGCCC    94.3％   8938    4467    CUuAGUUAUUCUGCUGGUG    0.5％

8890    4460    CGCUUUGUCCAAAAUGCuC    0.6％    8939    4467    uUCAGUUAUUCUGCUGGUG    0.2％

8891    4460    CGCUUUGUCCAAAAUGuCC    0.1％    8940    4467    CUCAGcUAUUCUGCUGGUG    0.2％

8892    4460    CGCUUUGUCCAgAAUGCCC    1.4％    8941    4467    CUCAGUUAcUCUGCUGGUG    1.0％

8893    4460    CGCUUUGUuCAAAAUGCCC    0.3％    8942    4467    CUCAGUUAUUCcGCUGGUG    0.1％

8894    4460    CGuUUUGUCCAAAAUGCCC    0.2％    8943    4467    CUCAGUUAUUCgGCUGGUG    0.1％

8895    4460    CGaUUUGUCCAAAAUGCCC    1.6％    8944    4467    CUCAGUUAUUCUGCcGGUG    0.2％

8896    4460    CGCUUcGUCCAAAAUGCCC    0.1％    8945    4467    CUCAGUUAUUCUGCUGGcG    0.1％

8897    4460    CGCUUUGUCCAAAAcGCCC    0.1％    4468    4468    GUUAUUCUGCUGGUGCACU    94.0％

8898    4460    CGCUUUGUCCAAAAUGCaC    0.2％    8946    4468    GUUAUUCUGCUGGUGCgCU    0.9％

8899    4460    CGgUUUGUCCAAAAUGCCC    0.3％    8947    4468    GcUAUUCUGCUGGUGCACU    0.2％

8900    4460    CuCUUUGUCCAAAAUGCCC    0.1％    8948    4468    GUUAcUCUGCUGGUGCACU    1.0％

8949    4468    GUUAUUCcGCUGGUGCACU    0.1％    8999    4474    AGUUAUUCUGCcGGUGCAC    0.2％

8950    4468    GUUAUUCgGCUGGUGCACU    0.1％    9000    4474    AGUUAUUCUGCUGGcGCAC    0.1％

8951    4468    GUUAUUCUGCcGGUGCACU    0.2％    4475    4475    GGAAUGGCUAAAGACAAGA    93.7％

8952    4468    GUUAUUCUGCUGGcGCACU    0.1％    9001    4475    GGAAUGGCUAAAGACAAGg    0.4％

4469    4469    UGGCCAGCACUACAGCUAA    94.0％   9002    4475    GGAAUGGCUgAAGACAAGA    0.1％

8953    4469    UGGCCAGCACUACgGCUAA    1.5％    9003    4475    GGAAUGGuUAAAGACAAGA    0.1％

8954    4469    UGGCCAGCA1UACAGCUAA    0.1％    9004    4475    GGAgUGGCUAAAGACAAGA    5.4％

8955    4469    UGGCCAGuACUACAGCUAA    0.1％    9005    4475    GGAAUGGCUAAAGACAAaA    0.2％

8956    4469    UGGCCAGuACUACgGCUAA    0.3％    9006    4475    GGAAUGGCUAAAGACuAGA    0.2％

8957    4469    UaGCCAGCACUACAGCUAA    1.2％    4476    4476    AAUGGCUAAAGACAAGACC    93.7％

8958    4469    UGGCaAGCACUACAGCUAA    0.1％    9007    4476    AAUGGCUAAAGACAAGgCC    0.4％

8959    4469    UGGCCAGCACcACAGCUAA    0.3％    9008    4476    AAUGGCUgAAGACAAGACC    0.1％

8960    4469    UGGCCAGCACUACAGCcAA    0.3％    9009    4476    AAUGGuUAAAGACAAGACC    0.1％

8961    4469    UGGCCAGCACUACAGCUuA    0.1％    9010    4476    AgUGGCUAAAGACAAGACC    5.4％

8962    4469    UGGCCAGCACUACcGCUAA    0.1％    9011    4476    AAUGGCUAAAGACAAaACC    0.2％

8963    4469    UaGCCAGCACUACgGCUAA    1.2％    9012    4476    AAUGGCUAAAGACuAGACC    0.2％

8964    4469    UGGCuAGCACcACAGCUAA    0.1％    4477    4477    GAAUGGCUAAAGACAAGAC    93.7％

8965    4469    UaGCCAGCACaACAGCUAA    0.4％    9013    4477    GAAUGGCUAAAGACAAGgC    0.4％

8966    4469    UaGCCAGCACUACAGCcAA    0.1％    9014    4477    GAAUGGCUgAAGACAAGAC    0.1％

8967    4469    UaGCCAGCACcACgGCUAA    0.1％    9015    4477    GAAUGGuUAAAGACAAGAC    0.1％

4470    4470    UUAUUCUGCUGGUGCACUU    94.0％   9016    4477    GAgUGGCUAAAGACAAGAC    5.4％

8968    4470    UUAUUCUGCUGGUGCgCUU    0.9％    9017    4477    GAAUGGCUAAAGACAAaAC    0.2％

8969    4470    cUAUUCUGCUGGUGCACUU    0.2％    9018    4477    GAAUGGCUAAAGACuAGAC    0.2％

8970    4470    UUAcUCUGCUGGUGCACUU    1.0％    4478    4478    UCCAUGGGGCCAAAGAAAU    93.4％

8971    4470    UUAUUCcGCUGGUGCACUU    0.1％    9019    4478    UCCAUGGGGCCAAAGAAgU    0.4％

8972    4470    UUAUUCgGCUGGUGCACUU    0.1％    9020    4478    UCCAUGGGGCCAAAGAgAU    0.1％

8973    4470    UUAUUCUGCcGGUGCACUU    0.2％    9021    4478    UCCAUGGGGCCAAAGgAAU    0.2％

8974    4470    UUAUUCUGCUGGcGCACUU    0.1％    9022    4478    UCCAUGGGGCCAAgGAAAU    0.1％

4471    4471    CAUGGAAUGGCUAAAGACA    94.0％   9023    4478    UCCAUGGGGCuAAAGAAAU    0.9％

8975    4471    CAUGGAAUGGCUgAAGACA    0.1％    9024    4478    UCuAUGGGGCCAAAGAAAU    0.2％

8976    4471    CAUGGAAUGGuUAAAGACA    0.1％    9025    4478    UuCAUGGGGCCAAAGAAAU    0.5％

8977    4471    CAUGGAgUGGCUAAAGACA    5.4％    9026    4478    UCCAUGGGGCCAAgGAggU    0.1％

8978    4471    aAUGGAAUGGCUAAAGACA    0.1％    9027    4478    UCCAUGGaGCCAAAGAAAU    0.4％

8979    4471    CAcGGAAUGGCUAAAGACA    0.2％    9028    4478    UCCAcGGGGCCAAAGAAgU    0.3％

8980    4471    CAUGGAAUGGCUAAAGACu    0.2％    9029    4478    UuCAUGGGGCCAAAGuAAU    0.1％

4472    4472    UGGAAUGGCUAAAGACAAG    93.9％   4479    4479    GCGUAGACGCUUUGUCCAA    93.4％

8981    4472    UGGAAUGGCUgAAGACAAG    0.1％    9030    4479    GCGUAGACGCUUUGUCCAg    2.0％

8982    4472    UGGAAUGGuUAAAGACAAG    0.1％    9031    4479    GCGUAGACGCUUUGUuCAA    0.1％

8983    4472    UGGAgUGGCUAAAGACAAG    5.4％    9032    4479    GCGUAGACGuUUUGUCCAA    0.2％

8984    4472    cGGAAUGGCUAAAGACAAG    0.2％    9033    4479    aCGUAGACGCUUUGUCCAA    1.5％

8985    4472    UGGAAUGGCUAAAGACAAa    0.2％    9034    4479    GCGUAcACGCUUUGUCCAA    0.1％

8986    4472    UGGAAUGGCUAAAGACuAG    0.2％    9035    4479    GCGUAGACGaUUUGUCCAA    1.5％

4473    4473    UCUCAUGGAAUGGCUAAAG    93.9％   9036    4479    GCGUAGACGCUUcGUCCAA    0.1％

8987    4473    UCUCAUGGAAUGGCUgAAG    0.1％    9037    4479    GCGUAGACGgUUUGUCCAA    0.3％

8988    4473    UCUCAUGGAAUGGuUAAAG    0.1％    9038    4479    GCGUAuACGCUUUGUCCAA    0.2％

8989    4473    UCUCAUGGAgUGGCUAAAG    5.4％    9039    4479    aCGUAGACGCUUUGUuCAA    0.2％

8990    4473    aCUCAUGGAAUGGCUAAAG    0.3％    9040    4479    GCGUAaACGCUUUGUCCAg    0.1％

8991    4473    UCUaAUGGAAUGGCUAAAG    0.1％    9041    4479    aCGUAuACGCUUUGUCCAA    0.1％

8992    4473    UCUCAcGGAAUGGCUAAAG    0.2％    9042    4479    GCGUAuACGaUUUGUCCAA    0.1％

4474    4474    AGUUAUUCUGCUGGUGCAC    93.9％   4480    4480    CAGUUAUUCUGCUGGUGCA    93.4％

8993    4474    AGUUAUUCUGCUGGUGCgC    0.9％    9043    4480    CAGUUAUUCUGCUGGUGCg    0.9％

8994    4474    gGUUAUUCUGCUGGUGCAC    0.1％    9044    4480    CgGUUAUUCUGCUGGUGCA    0.1％

8995    4474    AGcUAUUCUGCUGGUGCAC    0.2％    9045    4480    uAGUUAUUCUGCUGGUGCA    0.5％

8996    4474    AGUUAcUCUGCUGGUGCAC    1.0％    9046    4480    CAGcUAUUCUGCUGGUGCA    0.2％

8997    4474    AGUUAUUCcGCUGGUGCAC    0.1％    9047    4480    CAGUUAcUCUGCUGGUGCA    1.0％

8998    4474    AGUUAUUCgGCUGGUGCAC    0.1％    9048    4480    CAGUUAUUCcGCUGGUGCA    0.1％

9049    4480    CAGUUAUUCgGCUGGUGCA    0.1％    9099    4486    GAaGCUCUCAUGGAAUGGC    0.1％

9050    4480    CAGUUAUUCUGCcGGUGCA    0.2％    9100    4486    GAGGCaCUCAUGGAAUGGC    0.3％

9051    4480    CAGUUAUUCUGCUGGcGCA    0.1％    9101    4486    GAGGCUCUaAUGGAAUGGC    0.1％

4481    4481    UUCCAUGGGGCCAAAGAAA    93.4％   9102    4486    GAGGCUCUCAcGGAAUGGC    0.1％

9052    4481    UUCCAUGGGGCCAAAGAAg    0.4％    9103    4486    GAGGuUCUCAcGGAAUGGC    0.1％

9053    4481    UUCCAUGGGGCCAAAGAgA    0.1％    4487    4487    GCUCUCAUGGAAUGGCUAA    93.0％

9054    4481    UUCCAUGGGGCCAAAGgAA    0.2％    9104    4487    GCUCUCAUGGAAUGGCUgA    0.1％

9055    4481    UUCCAUGGGGCCAAgGAAA    0.1％    9105    4487    GCUCUCAUGGAAUGGuUAA    0.1％

9056    4481    UUCCAUGGGGCuAAAGAAA    0.9％    9106    4487    GCUCUCAUGGAgUGGCUAA    5.4％

9057    4481    UUCuAUGGGGCCAAAGAAA    0.2％    9107    4487    GuUCUCAUGGAAUGGCUAA    0.9％

9058    4481    UUuCAUGGGGCCAAAGAAA    0.5％    9108    4487    GCaCUCAUGGAAUGGCUAA    0.3％

9059    4481    UUCCAUGGGGCCAAgGAgg    0.1％    9109    4487    GCUCUaAUGGAAUGGCUAA    0.1％

9060    4481    UUCCAUGGaGCCAAAGAAA    0.4％    9110    4487    GCUCUCAcGGAAUGGCUAA    0.1％

9061    4481    UUCCAcGGGGCCAAAGAAg    0.3％    9111    4487    GuUCUCAcGGAAUGGCUAA    0.1％

9062    4481    UUuCAUGGGGCCAAAGuAA    0.1％    4488    4488    CUCUCAUGGAAUGGCUAAA    93.0％

4482    4482    CACCUCUGACUAAGGGGAU    93.2％   9112    4488    CUCUCAUGGAAUGGCUgAA    0.1％

9063    4482    CACCUCUGACUAgGGGGAU    0.1％    9113    4488    CUCUCAUGGAAUGGuUAAA    0.1％

9064    4482    CACCUCUaACUAAGGGGAU    0.9％    9114    4488    CUCUCAUGGAgUGGCUAAA    5.4％

9065    4482    CACCUCUGACaAAGGGGAU    0.4％    9115    4488    uUCUCAUGGAAUGGCUAAA    0.9％

9066    4482    CACCUCUGACcAAGGGGAU    0.2％    9116    4488    CaCUCAUGGAAUGGCUAAA    0.3％

9067    4482    CACCUCUGACUAAaGGGAU    2.0％    9117    4488    CUCUaAUGGAAUGGCUAAA    0.1％

9068    4482    CACCUCUGACUAAGGGaAU    3.0％    9118    4488    CUCUCAcGGAAUGGCUAAA    0.1％

9069    4482    CACCUCUGACUAAGGGuAU    0.1％    9119    4488    uUCUCAcGGAAUGGCUAAA    0.1％

9070    4482    CACCUCUuACUAAGGGGAU    0.1％    4489    4489    AUGGGGCCAAAGAAAUAGC    93.0％

9071    4482    CACCUCUGACcAAGGGaAU    0.1％    9120    4489    AUGGGGCCAAAGAAgUAGC    0.4％

4483    4483    GUCACCUCUGACUAAGGGG    93.2％   9121    4489    AUGGGGCCAAAGAgAUAGC    0.1％

9072    4483    GUCACCUCUGACUAgGGGG    0.1％    9122    4489    AUGGGGCCAAAGgAAUAGC    0.2％

9073    4483    GUCACCUCUaACUAAGGGG    0.9％    9123    4489    AUGGGGCCAAgGAAAUAGC    0.1％

9074    4483    GUCACCUCUGACaAAGGGG    0.4％    9124    4489    AUGGGGCuAAAGAAAUAGC    0.9％

9075    4483    GUCACCUCUGACcAAGGGG    0.2％    9125    4489    AUGGaGCCAAAGAAAUAGC    0.4％

9076    4483    GUCACCUCUGACUAAaGGG    2.0％    9126    4489    AUGGGGCCAAAGAAAUAuC    0.2％

9077    4483    GUCACCUCUGACUAAGGGa    3.0％    9127    4489    AUGGGGCCAAAGAAAUcGC    0.5％

9078    4483    GUCACCUCUGACUAAGGGu    0.1％    9128    4489    AUGGGGCCAAAGuAAUAGC    0.1％

9079    4483    GUCACCUCUuACUAAGGGG    0.1％    9129    4489    AcGGGGCCAAAGAAgUAGC    0.3％

9080    4483    GUCACCUCUGACcAAGGGa    0.1％    9130    4489    AUGGGGCCAAAGAAAUcuC    0.4％

4484    4484    UCACCUCUGACUAAGGGGA    93.2％   4490    4490    AGGCUCUCAUGGAAUGGCU    93.0％

9081    4484    UCACCUCUGACUAgGGGGA    0.1％    9131    4490    AGGCUCUCAUGGAAUGGuU    0.1％

9082    4484    UCACCUCUaACUAAGGGGA    0.9％    9132    4490    AGGCUCUCAUGGAgUGGCU    5.4％

9083    4484    UCACCUCUGACaAAGGGGA    0.4％    9133    4490    AGGuUCUCAUGGAAUGGCU    0.9％

9084    4484    UCACCUCUGACcAAGGGGA    0.2％    9134    4490    AaGCUCUCAUGGAAUGGCU    0.1％

9085    4484    UCACCUCUGACUAAaGGGA    2.0％    9135    4490    AGGCaCUCAUGGAAUGGCU    0.3％

9086    4484    UCACCUCUGACUAAGGGaA    3.0％    9136    4490    AGGCUCUaAUGGAAUGGCU    0.1％

9087    4484    UCACCUCUGACUAAGGGuA    0.1％    9137    4490    AGGCUCUCAcGGAAUGGCU    0.1％

9088    4484    UCACCUCUuACUAAGGGGA    0.1％    9138    4490    AGGuUCUCAcGGAAUGGCU    0.1％

9089    4484    UCACCUCUGACcAAGGGaA    0.1％    4491    4491    GGCUCUCAUGGAAUGGCUA    92.9％

4485    4485    CUGGUGCACUUGCCAGUUG    93.0％   9139    4491    GGCUCUCAUGGAAUGGCUg    0.1％

9090    4485    CUGGUGCACUUGCuAGUUG    2.4％    9140    4491    GGCUCUCAUGGAAUGGuUA    0.1％

9091    4485    CUGGUGCgCUUGCCAGUUG    2.5％    9141    4491    GGCUCUCAUGGAgUGGCUA    5.4％

9092    4485    CcGGUGCACUUGCCAGUUG    1.7％    9142    4491    GGuUCUCAUGGAAUGGCUA    0.9％

9093    4485    CUGGcGCACUUGCCAGUUG    0.1％    9143    4491    aGCUCUCAUGGAAUGGCUA    0.1％

9094    4485    CUGGUGCgCUUGCCAGcUG    0.2％    9144    4491    GGCaCUCAUGGAAUGGCUA    0.3％

9095    4485    CcGGgGCACUUGCCAGUUG    0.1％    9145    4491    GGCUCUaAUGGAAUGGCUA    0.1％

4486    4486    GAGGCUCUCAUGGAAUGGC    93.0％   9146    4491    GGCUCUCAcGGAAUGGCUA    0.1％

9096    4486    GAGGCUCUCAUGGAAUGGu    0.1％    9147    4491    GGuUCUCAcGGAAUGGCUA    0.1％

9097    4486    GAGGCUCUCAUGGAgUGGC    5.4％    4492    4492    UUGAGGCUCUCAUGGAAUG    92.9％

9098    4486    GAGGuUCUCAUGGAAUGGC    0.9％    9148    4492    UUGAGGCUCUCAUGGAgUG    3.8％

9149   4492    UUGAGGuUCUCAUGGAAUG    0.9％    9200    4497    CUUCUACGGAAGGgGUACC    0.2％

9150   4492    UaGAGGCUCUCAUGGAAUG    0.1％    9201    4497    CUUCUACGGAgGGAGUACC    0.1％

9151   4492    UcGAGGCUCUCAUGGAAUG    0.1％    9202    4497    CUUCUACGGgAGGAGUACC    0.2％

9152   4492    UUGAaGCUCUCAUGGAAUG    0.1％    9203    4497    CUUuUACGGAAGGAGUACC    0.1％

9153   4492    UUGAGGCaCUCAUGGAAUG    0.3％    9204    4497    aUUCUACGGAAGGAGUACC    0.1％

9154   4492    UUGAGGCUCUaAUGGAAUG    0.1％    9205    4497    CUgCUACGGAAGGAGUACC    0.1％

9155   4492    UUGAGGCUCUCAcGGAAUG    0.1％    9206    4497    CUUCcACGGAAGGAGUACC    0.1％

9156   4492    UcGAGGCUCUCAUGGAgUG    1.5％    9207    4497    CUUCUACaGAAGGAGUACC    0.1％

9157   4492    UUGAGGuUCUCAcGGAAUG    0.1％    9208    4497    CUUCUACGGAAGGAaUACC    0.4％

4493   4493    UGAGGCUCUCAUGGAAUGG    92.9％   9209    4497    CUUCUACGGAAGGAGUuCC    0.1％

9158   4493    UGAGGCUCUCAUGGAgUGG    3.8％    9210    4497    CUUgUACGGAAGGAGUACC    0.1％

9159   4493    UGAGGuUCUCAUGGAAUGG    0.9％    9211    4497    CUcCUACGGAAGGAGUgCu    0.5％

9160   4493    aGAGGCUCUCAUGGAAUGG    0.1％    9212    4497    CUUCUACaGAuGGAGUACC    0.2％

9161   4493    cGAGGCUCUCAUGGAAUGG    0.1％    9213    4497    CUgCUACGGcAGGgGUACC    1.2％

9162   4493    UGAaGCUCUCAUGGAAUGG    0.1％    4498    4498    UCUUGAGGCUCUCAUGGAA    92.7％

9163   4493    UGAGGCaCUCAUGGAAUGG    0.3％    9214    4498    UCUUGAGGCUCUCAUGGAg    3.7％

9164   4493    UGAGGCUCUaAUGGAAUGG    0.1％    9215    4498    UCUUGAGGuUCUCAUGGAA    0.9％

9165   4493    UGAGGCUCUCAcGGAAUGG    0.1％    9216    4498    cCUUGAGGCUCUCAUGGAA    0.2％

9166   4493    cGAGGCUCUCAUGGAgUGG    1.5％    9217    4498    UCUaGAGGCUCUCAUGGAA    0.1％

9167   4493    UGAGGuUCUCAcGGAAUGG    0.1％    9218    4498    UCUcGAGGCUCUCAUGGAA    0.1％

4494   4494    CUUGAGGCUCUCAUGGAAU    92.9％   9219    4498    UCUUGAaGCUCUCAUGGAA    0.1％

9168   4494    CUUGAGGCUCUCAUGGAgU    3.8％    9220    4498    UCUUGAGGCaCUCAUGGAA    0.3％

9169   4494    CUUGAGGuUCUCAUGGAAU    0.9％    9221    4498    UCUUGAGGCUCUaAUGGAA    0.1％

9170   4494    CUaGAGGCUCUCAUGGAAU    0.1％    9222    4498    UCUUGAGGCUCUCAcGGAA    0.1％

9171   4494    CUcGAGGCUCUCAUGGAAU    0.1％    9223    4498    cCUUGAGGCUCUCAUGGAg    0.1％

9172   4494    CUUGAaGCUCUCAUGGAAU    0.1％    9224    4498    UCUcGAGGCUCUCAUGGAg    1.5％

9173   4494    CUUGAGGCaCUCAUGGAAU    0.3％    9225    4498    UCUUGAGGuUCUCAcGGAA    0.1％

9174   4494    CUUGAGGCUCUaAUGGAAU    0.1％    4499    4499    CUGCUGGUGCACUUGCCAG    92.7％

9175   4494    CUUGAGGCUCUCAcGGAAU    0.1％    9226    4499    CUGCUGGUGCACUUGCuAG    2.4％

9176   4494    CUcGAGGCUCUCAUGGAgU    1.5％    9227    4499    CUGCUGGUGCgCUUGCCAG    0.9％

9177   4494    CUUGAGGuUCUCAcGGAAU    0.1％    9228    4499    CcGCUGGUGCACUUGCCAG    0.1％

4495   4495    CAUGGGGCCAAAGAAAUAG    92.9％   9229    4499    CgGCUGGUGCACUUGCCAG    0.1％

9178   4495    CAUGGGGCCAAAGAAgUAG    0.4％    9230    4499    CUGCcGGUGCACUUGCCAG    0.2％

9179   4495    CAUGGGGCCAAAGAgAUAG    0.1％    9231    4499    CUGCUGGcGCACUUGCCAG    0.1％

9180   4495    CAUGGGGCCAAAGgAAUAG    0.2％    9232    4499    CaaCUGGUGCACUUGCCAG    0.1％

9181   4495    CAUGGGGCCAAgGAAAUAG    0.1％    9233    4499    CaaCUGGUGCgCUUGCCAG    1.8％

9182   4495    CAUGGGGCuAAAGAAAUAG    0.9％    4500    4500    UGCUGGUGCACUUGCCAGU    92.7％

9183   4495    uAUGGGGCCAAAGAAAUAG    0.1％    9234    4500    UGCUGGUGCACUUGCuAGU    2.4％

9184   4495    CAUGGaGCCAAAGAAAUAG    0.4％    9235    4500    UGCUGGUGCgCUUGGCAGU    0.7％

9185   4495    CAUGGGGCCAAAGAAAUAU    0.2％    9236    4500    cGCUGGUGCACUUGCCAGU    0.1％

9186   4495    CAUGGGGCCAAAGAAAUcG    0.4％    9237    4500    gGCUGGUGCACUUGCCAGU    0.1％

9187   4495    CAUGGGGCCAAAGuAAUAG    0.1％    9238    4500    UGCcGGUGCACUUGCCAGU    0.2％

9188   4495    CAcGGGGCCAAAGAAgUAG    0.3％    9239    4500    UGCUGGcGCACUUGCCAGU    0.1％

9189   4495    uAUGGGGCCAAAGAAAUcG    0.1％    9240    4500    UGCUGGUGCgCUUGCCAGc    0.2％

9190   4495    CAUGGGGCCAAAGAAAUcU    0.4％    9241    4500    aaCUGGUGCACUUGCCAGU    0.1％

4496   4496    GCUGGUGCACUUGCCAGUU    92.9％   9242    4500    aaCUGGUGCgCUUGCCAGU    1.8％

9191   4496    GCUGGUGCACUUGCuAGUU    2.4％    4501    4501    UCUGCUGGUGCACUUGCCA    92.7％

9192   4496    GCUGGUGCgCUUGCCAGUU    0.7％    9243    4501    UCUGCUGGUGCACUUGCUA    2.4％

9193   4496    aCUGGUGCACUUGCCAGUU    0.1％    9244    4501    UCUGCUGGUGCgCUUGCCA    0.9％

9194   4496    GCcGGUGCACUUGCCAGUU    0.2％    9245    4501    UCcGCUGGUGCACUUGCCA    0.1％

9195   4496    GCUGGcGCACUUGCCAGUU    0.1％    9246    4501    UCgGCUGGUGCACUUGCCA    0.1％

9196   4496    aCUGGUGCgCUUGCCAGUU    1.8％    9247    4501    UCUGCcGGUGCACUUGCCA    0.2％

9197   4496    GCUGGUGCgCUUGCCAGcU    0.2％    9248    4501    UCUGCUGGcGCACUUGCCA    0.1％

9198   4496    aCcGGUGCACUUGCCAGUU    1.5％    9249    4501    UCaaCUGGUGCACUUGCCA    0.1％

4497   4497    CUUCUACGGAAGGAGUACC    92.8％   9250    4501    UCaaCUGGUGCgCUUGCCA    1.8％

9199   4497    CUUCUACGGAAGGAGUgCC    3.4％    4502    4502    CCAUGGGGCCAAAGAAAUA    92.6％

9251    4502    CCAUGGGGCCAAAGAAgUA    0.4％    9303    4506    CcAUGAGGGAAGAAUAUCG    0.8％

9252    4502    CCAUGGGGCCAAAGAgAUA    0.1％    9304    4506    CUAUGAGGGAAGAAUAcCG    0.2％

9253    4502    CCAUGGGGCCAAAGgAAUA    0.2％    9305    4506    CUuUGAGGGAAGAAUAUCG    0.6％

9254    4502    CCAUGGGGCCAAgGAAAUA    0.1％    9306    4506    CUAUGAGGGAAcAAUAUuG    0.1％

9255    4502    CCAUGGGGCuAAAGAAAUA    0.9％    9307    4506    CUAUGAGGGAAGAgUAcCG    1.3％

9256    4502    CuAUGGGGCCAAAGAAAUA    0.1％    9308    4506    uUAUGAGGGAAGAAUAUgG    0.1％

9257    4502    uCAUGGGGCCAAAGAAAUA    0.5％    9309    4506    CcAUGAGGGAAGAAUAUCa    0.1％

9258    4502    CCAUGGaGCCAAAGAAAUA    0.4％    9310    4506    CUAcuAGGGAAGAAUAUCG    0.1％

9259    4502    CCAUGGGGCCAAAGAAAUc    0.8％    9311    4506    CcAUGAGGGAAGAgUAUCa    0.1％

9260    4502    CCAcGGGGCCAAAGAAgUA    0.3％    4507    4507    UCUAUGAGGGAAGAAUAUC    92.4％

9261    4502    CuAUGGGGCCAAAGAAAUc    0.1％    9312    4507    UCUAUGAGGGAAGAgUAUC    3.4％

9262    4502    uCAUGGGGCCAAAGuAAUA    0.1％    9313    4507    UCUAUGAGGGAgGAAUAUC    0.8％

4503    4503    AGUCUAUGAGGGAAGAAUA    92.6％   9314    4507    UCUAUGgGGGAAGAAUAUC    0.1％

9263    4503    AGUCUAUGAGGGAAGAgUA    4.7％    9315    4507    UCcAUGAGGGAAGAAUAUC    0.9％

9264    4503    AGUCUAUGAGGGAgGAAUA    0.8％    9316    4507    UCUAUGAGGGAAGAAUAcC    0.2％

9265    4503    AGUCUAUGgGGGAAGAAUA    0.1％    9317    4507    UCUuUGAGGGAAGAAUAUC    0.6％

9266    4503    AGUuUAUGAGGGAAGAAUA    0.1％    9318    4507    UCcAUGAGGGAAGAgUAUC    0.1％

9267    4503    AGUCcAUGAGGGAAGAAUA    0.9％    9319    4507    UCUAUGAGGGAAcAAUAUu    0.1％

9268    4503    AGUCUAUGAGGGAAcAAUA    0.1％    9320    4507    UCUAUGAGGGAAGAgUAcC    1.3％

9269    4503    AGUCUuUGAGGGAAGAAUA    0.6％    9321    4507    UuUAUGAGGGAAGAAUAUg    0.1％

9270    4503    AGUCcAUGAGGGAAGAgUA    0.1％    9322    4507    UCUAcuAGGGAAGAAUAUC    0.1％

9271    4503    AGUCUAcuAGGGAAGAAUA    0.1％    4508    4508    GUCAUUUUGUCAGCAUAGA    92.2％

4504    4504    CCUUCUACGGAAGGAGUAC    92.5％   9323    4508    GUCAUUUUGUCAGCAUAGg    0.2％

9272    4504    CCUUCUACGGAAGGAGUgC    3.4％    9324    4508    GUCAUUUUGUCAGCAUgGA    0.1％

9273    4504    CCUUCUACGGAAGGgGUAC    0.2％    9325    4508    GUCAUUUUGUCAGuAUAGA    0.2％

9274    4504    CCUUCUACGGAgGGAGUAC    0.1％    9326    4508    GUCgUUUUGUCAGCAUAGA    0.1％

9275    4504    CCUUCUACGGgAGGAGUAC    0.2％    9327    4508    GUCAaUUUGUCAGCAUAGA    0.1％

9276    4504    CCUUuUACGGAAGGAGUAC    0.1％    9328    4508    GUCAUUcUGUCAGCAUAGA    0.1％

9277    4504    uCUUCUACGGAAGGAGUAC    0.1％    9329    4508    GUCAUUUUGcCAGCAUAGA    0.1％

9278    4504    CaUUCUACGGAAGGAGUAC    0.1％    9330    4508    GUCAUUUUGUCAaCAUAGA    5.1％

9279    4504    CCUgCUACGGAAGGAGUAC    0.1％    9331    4508    GUCAUUUUGUCAGCAUAaA    0.3％

9280    4504    CCUUCcACGGAAGGAGUAC    0.1％    9332    4508    GUCAUUUUGUCAGCAUAcA    0.1％

9281    4504    CCUUCUACaGAAGGAGUAC    0.1％    9333    4508    GUCgUUUUGUCAaCAUAGA    0.1％

9282    4504    CCUUCUACGGAAGGAaUAC    0.4％    9334    4508    GUCAUUUcGUCAaCAUAGA    0.1％

9283    4504    CCUUCUACGGAAGGAGUuC    0.1％    9335    4508    GUCAUUUUGUCAaCAUAGu    0.4％

9284    4504    CCUUgUACGGAAGGAGUAC    0.1％    9336    4508    GUCAUUUUGUCAuCAUAcA    0.1％

9285    4504    gCUUCUACGGAAGGAGUAC    0.2％    4509    4509    GAGUCUAUGAGGGAAGAAU    92.2％

9286    4504    CCUcCUACGGAAGGAGUgC    0.5％    9337    4509    GAGUCUAUGAGGGAAGAgU    4.7％

9287    4504    CCUUCUACaGAuGGAGUAC    0.2％    9338    4509    GAGUCUAUGAGGGAgGAAU    0.8％

9288    4504    CCUgCUACGGcAGGgGUAC    1.2％    9339    4509    GAGUCUAUGgGGGAAGAAU    0.1％

4505    4505    GUCUAUGAGGGAAGAAUAU    92.4％   9340    4509    GAGUuUAUGAGGGAAGAAU    0.1％

9289    4505    GUCUAUGAGGGAAGAgUAU    3.4％    9341    4509    aAGUCUAUGAGGGAAGAAU    0.4％

9290    4505    GUCUAUGAGGGAgGAAUAU    0.8％    9342    4509    GAGUCcAUGAGGGAAGAAU    0.9％

9291    4505    GUCUAUGgGGGAAGAAUAU    0.1％    9343    4509    GAGUCUAUGAGGGAAcAAU    0.1％

9292    4505    GUuUAUGAGGGAAGAAUAU    0.1％    9344    4509    GAGUCUuUGAGGGAAGAAU    0.6％

9293    4505    GUCcAUGAGGGAAGAAUAU    0.9％    9345    4509    GAGUCcAUGAGGGAAGAgU    0.1％

9294    4505    GUCUAUGAGGGAAcAAUAU    0.1％    9346    4509    GAGUCUAcuAGGGAAGAAU    0.1％

9295    4505    GUCUAUGAGGGAAGAAUAc    0.2％    4510    4510    UCAUUUUGUCAGCAUAGAG    92.1％

9296    4505    GUCUuUGAGGGAAGAAUAU    0.6％    9347    4510    UCAUUUUGUCAGCAUAGgG    0.2％

9297    4505    GUCcAUGAGGGAAGAgUAU    0.1％    9348    4510    UCAUUUUGUCAGCAUgGAG    0.1％

9298    4505    GUCUAUGAGGGAAGAgUAc    1.3％    9349    4510    UCAUUUUGUCAGuAUAGAG    0.2％

9299    4505    GUCUAcuAGGGAAGAAUAU    0.1％    9350    4510    UCgUUUUGUCAGCAUAGAG    0.1％

4506    4506    CUAUGAGGGAAGAAUAUCG    92.4％   9351    4510    UCAaUUUGUCAGCAUAGAG    0.1％

9300    4506    CUAUGAGGGAAGAgUAUCG    3.4％    9352    4510    UCAUUcUGUCAGCAUAGAG    0.1％

9301    4506    CUAUGAGGGAgGAAUAUCG    0.8％    9353    4510    UCAUUUUGcCAGCAUAGAG    0.1％

9302    4506    CUAUGgGGGAAGAAUAUCG    0.1％    9354    4510    UCAUUUUGUCAaCAUAGAG    3.7％

9355    4510    UCAUUUUGUCAGCAUAaAG    0.3％    9407    4514    GAGACUUcAAGAUGUCUUU    0.1％

9356    4510    UCAUUUUGUCAGCAUAcAG    0.1％    9408    4514    GAGACUUGAAaAUGUCUUU    0.3％

9357    4510    UCAUUUUGUCAGCAUAGAu    0.1％    9409    4514    GAGACUUGAAGAUGUaUUU    2.5％

9358    4510    gCAUUUUGUCAaCAUAGAG    0.1％    9410    4514    GAGACUUGAAuAUGUCUUU    0.1％

9359    4510    UCAUUUcGUCAaCAUAGAG    0.1％    9411    4514    GAaACUUGAgGAUGUCUUU    0.1％

9360    4510    UCAUUUUGUCAaCAUAGAa    1.3％    9412    4514    GAGACUgGAAGgUGUCUUU    0.1％

9361    4510    UCAUUUUGUCAaCAUAGuG    0.4％    9413    4514    GAGACaaGAAGAUGUCUUU    0.2％

9362    4510    UCgUUUUGUCAaCAUAGAa    0.1％    9414    4514    GAGACUcGAAGAcGUuUUU    0.1％

4511    4511    AGACUUGAAGAUGUCUUUG    91.9％   4515    4515    CAGAGACUUGAAGAUGUCU    91.9％

9363    4511    AGACUUGAAGAUGUuUUUG    0.8％    9415    4515    CAGAGACUUGAAGAUGUuU    0.8％

9364    4511    AGACUUGAgGAUGUCUUUG    0.4％    9416    4515    CAGAGACUUGAgGAUGUCU    0.4％

9365    4511    AGgCUUGAAGAUGUCUUUG    0.2％    9417    4515    CAGAGgCUUGAAGAUGUCU    0.2％

9366    4511    AGACUUGAgGAUGUuUUUG    1.7％    9418    4515    CAGAGACUUGAgGAUGUuU    1.7％

9367    4511    AaACUUGAAGAUGUCUUUG    1.5％    9419    4515    CAGAaACUUGAAGAUGUCU    1.5％

9368    4511    AGACUUcAAGAUGUCUUUG    0.1％    9420    4515    CAGAGACUUcAAGAUGUCU    0.1％

9369    4511    AGACUUGAAaAUGUCUUUG    0.3％    9421    4515    CAGAGACUUGAAaAUGUCU    0.3％

9370    4511    AGACUUGAAGAUGUaUUUG    2.5％    9422    4515    CAGAGACUUGAAGAUGUaU    2.5％

9371    4511    AGACUUGAAuAUGUCUUUG    0.1％    9423    4515    CAGAGACUUGAAuAUGUCU    0.1％

9372    4511    AaACUUGAgGAUGUCUUUG    0.1％    9424    4515    CAGAaACUUGAgGAUGUCU    0.1％

9373    4511    AGACUgGAAGgUGUCUUUG    0.1％    9425    4515    CAGAGACUgGAAGgUGUCU    0.1％

9374    4511    AGACaaGAAGAUGUCUUUG    0.2％    9426    4515    CAGAGACaaGAAGAUGUCU    0.2％

9375    4511    AGACUcGAAGAcGUuUUUG    0.1％    9427    4515    CAGAGACUcGAAGAcGUuU    0.1％

4512    4512    GACUUGAAGAUGUCUUUGC    91.9％   4516    4516    GUGCAGAUGCAACGAUUCA    91.7％

9376    4512    GACUUGAAGAUGUuUUUGC    0.8％    9428    4516    GUGCAGAUGCAACGgUUCA    1.8％

9377    4512    GACUUGAgGAUGUCUUUGC    0.4％    9429    4516    GUGCAGAUGCAgCGAUUCA    3.2％

9378    4512    GgCUUGAAGAUGUCUUUGC    0.2％    9430    4516    GUGCAGgUGCAACGAUUCA    0.1％

9379    4512    GACUUGAgGAUGUuUUUGC    1.7％    9431    4516    GUGCAGAUGCAgCGgUUCA    0.2％

9380    4512    aACUUGAAGAUGUCUUUGC    1.5％    9432    4516    GUaCAGAUGCAACGAUUCA    0.1％

9381    4512    GACUUcAAGAUGUCUUUGC    0.1％    9433    4516    GUGCAaAUGCAACGAUUCA    0.4％

9382    4512    GACUUGAAaAUGUCUUUGC    0.3％    9434    4516    GUaCAGAUGCAgCGAUUCA    1.9％

9383    4512    GACUUGAAGAUGUaUUUGC    2.5％    9435    4516    GUGCAaAUGCAgCGAUUCA    0.2％

9384    4512    GACUUGAAuAUGUCUUUGC    0.1％    9436    4516    GUaCAaAUGCAgCGAUUCA    0.2％

9385    4512    aACUUGAgGAUGUCUUUGC    0.1％    9437    4516    GUGCAaAUGCAgaGAUUCA    0.2％

9386    4512    GACUgGAAGgUGUCUUUGC    0.1％    4517    4517    UUCUGCUGGUGCACUUGCC    91.7％

9387    4512    GACaaGAAGAUGUCUUUGC    0.2％    9438    4517    UUCUGCUGGUGCACUUGCu    2.4％

9388    4512    GACUcGAAGAcGUuUUUGC    0.1％    9439    4517    UUCUGCUGGUGCgCUUGCC    0.9％

4513    4513    AGAGACUUGAAGAUGUCUU    91.9％   9440    4517    cUCUGCUGGUGCACUUGCC    1.0％

9389    4513    AGAGACUUGAAGAUGUuUU    0.8％    9441    4517    UUCcGCUGGUGCACUUGCC    0.1％

9390    4513    AGAGACUUGAgGAUGUCUU    0.4％    9442    4517    UUCgGCUGGUGCACUUGCC    0.1％

9391    4513    AGAGgCUUGAAGAUGUCUU    0.2％    9443    4517    UUCUGCcGGUGCACUUGCC    0.2％

9392    4513    AGAGACUUGAgGAUGUuUU    1.7％    9444    4517    UUCUGCUGGcGCACUUGCC    0.1％

9393    4513    AGAaACUUGAAGAUGUCUU    1.5％    4518    4518    UGCAGAUGCAACGAUUCAA    91.6％

9394    4513    AGAGACUUcAAGAUGUCUU    0.1％    9445    4518    UGCAGAUGCAACGAUUCAg    0.2％

9395    4513    AGAGACUUGAAaAUGUCUU    0.3％    9446    4518    UGCAGAUGCAACGgUUCAA    1.8％

9396    4513    AGAGACUUGAAGAUGUaUU    2.5％    9447    4518    UGCAGAUGCAgCGAUUCAA    3.2％

9397    4513    AGAGACUUGAAuAUGUCUU    0.1％    9448    4518    UGCAGgUGCAACGAUUCAA    0.1％

9398    4513    AGAaACUUGAgGAUGUCUU    0.1％    9449    4518    UGCAGAUGCAgCGgUUCAA    0.2％

9399    4513    AGAGACUgGAAGgUGUCUU    0.1％    9450    4518    UaCAGAUGCAACGAUUCAA    0.1％

9400    4513    AGAGACaaGAAGAUGUCUU    0.2％    9451    4518    UGCAaAUGCAACGAUUCAA    0.4％

9401    4513    AGAGACUcGAAGAcGUuUU    0.1％    9452    4518    UaCAGAUGCAgCGAUUCAA    1.9％

4514    4514    GAGACUUGAAGAUGUCUUU    91.9％   9453    4518    UGCAaAUGCAgCGAUUCAA    0.2％

9402    4514    GAGACUUGAAGAUGUuUUU    0.8％    9454    4518    UaCAaAUGCAgCGAUUCAA    0.2％

9403    4514    GAGACUUGAgGAUGUCUUU    0.4％    9455    4518    UGCAaAUGCAgaGAUUCAA    0.2％

9404    4514    GAGgCUUGAAGAUGUCUUU    0.2％    4519    4519    UAUGAGGGAAGAAUAUCGA    91.5％

9405    4514    GAGACUUGAgGAUGUuUUU    1.7％    9456    4519    UAUGAGGGAAGAAUAUCGg    1.0％

9406    4514    GAaACUUGAAGAUGUCUUU    1.5％    9457    4519    UAUGAGGGAAGAgUAUCGA    1.5％

9458    4519    UAUGAGGGAgGAAUAUcGA    0.8％    9509    4524    GGAUcCUUGAUCGUCUUUU    0.1％

9459    4519    UAUGgGGGAAGAAUAUCGA    0.1％    9510    4524    GGAUUCUUaAUCGUCUUUU    0.3％

9460    4519    UAUGAGGGAAGAgUAUCGg    1.8％    9511    4524    GGAUUCUUGAUCaUCUUUU    0.2％

9461    4519    cAUGAGGGAAGAAUAUCGA    0.8％    9512    4524    GGAUUCUUGAUCGcCUUUU    1.0％

9462    4519    UAUGAGGGAAGAAUAcCGA    0.2％    9513    4524    GGAUUgUUGAUCGUCUUUU    0.1％

9463    4519    UAUGAGGGAAGAAUAUgGA    0.1％    9514    4524    GGAUUaUUGAUCGcCUUUU    5.6％

9464    4519    UuUGAGGGAAGAAUAUCGA    0.3％    9515    4524    GGAUUaUUGAUCGgCUUUU    1.0％

9465    4519    UuUGAGGGAAGAAUAUCGg    0.3％    4525    4525    GGGGUGCAGAUGCAACGAU    90.8％

9466    4519    UAUGAGGGAAcAAUAUuGg    0.1％    9516    4525    GGGGUGCAGAUGCAACGgU    0.5％

9467    4519    UAUGAGGGAAGAgUAcCGg    1.3％    9517    4525    GGGGUGCAGAUGCAgCGAU    1.5％

9468    4519    cAUGAGGGAAGAAUAUCaA    0.1％    9518    4525    GGGGUGCAGgUGCAACGAU    0.1％

9469    4519    UAcuAGGGAAGAAUAUCGA    0.1％    9519    4525    GGaGUGCAGAUGCAACGAU    1.0％

9470    4519    cAUGAGGGAAGAgUAUCaA    0.1％    9520    4525    GGGGUGCAaAUGCAACGAU    0.3％

4520    4520    AUGGGGGUGCAGAUGCAAC    91.3％   9521    4525    GGaGUGCAGAUGCAACGgU    1.3％

9471    4520    AUGGGGGUGCAGAUGCAgC    1.5％    9522    4525    GGaGUGCAGAUGCAgCGAU    1.6％

9472    4520    AUGGGGGUGCAGgUGCAAC    0.1％    9523    4525    GGaGUGCAGAUGCAgCGgU    0.2％

9473    4520    AUGGGaGUGCAGAUGCAAC    2.3％    9524    4525    GGaGUaCAGAUGCAACGAU    0.1％

9474    4520    AUGGGGGUGCAaAUGCAAC    0.3％    9525    4525    GGaGUGCAaAUGCAACGAU    0.1％

9475    4520    AUGGGaGUGCAGAUGCAgC    1.8％    9526    4525    GGaGUaCAGAUGCAgCGAU    1.9％

9476    4520    AUGGGaGUaCAGAUGCAAC    0.1％    9527    4525    GGaGUGCAaAUGCAgCGAU    0.2％

9477    4520    AUGGGaGUGCAaAUGCAAC    0.1％    4526    4526    GGGUGCAGAUGCAACGAUU    90.8％

9478    4520    AUGGGaGUaCAGAUGCAgC    1.9％    9528    4526    GGGUGCAGAUGCAACGgUU    0.5％

9479    4520    AUGGGaGUGCAaAUGCAgC    0.2％    9529    4526    GGGUGCAGAUGCAgCGAUU    1.5％

4521    4521    UGGGGGUGCAGAUGCAACG    91.3％   9530    4526    GGGUGCAGgUGCAACGAUU    0.1％

9480    4521    UGGGGGUGCAGAUGCAgCG    1.5％    9531    4526    GaGUGCAGAUGCAACGAUU    1.0％

9481    4521    UGGGGGUGCAGgUGCAACG    0.1％    9532    4526    GGGUGCAaAUGCAACGAUU    0.3％

9482    4521    UGGGaGUGCAGAUGCAACG    2.3％    9533    4526    GaGUGCAGAUGCAACGgUU    1.3％

9483    4521    UGGGGGUGCAaAUGCAACG    0.3％    9534    4526    GaGUGCAGAUGCAgCGAUU    1.6％

9484    4521    UGGGaGUGCAGAUGCAgCG    1.8％    9535    4526    GaGUGCAGAUGCAgCGgUU    0.2％

9485    4521    UGGGaGUaCAGAUGCAACG    0.1％    9536    4526    GaGUaCAGAUGCAACGAUU    0.1％

9486    4521    UGGGaGUGCAaAUGCAACG    0.1％    9537    4526    GaGUGCAaAUGCAACGAUU    0.1％

9487    4521    UGGGaGUaCAGAUGCAgCG    1.9％    9538    4526    GaGUaCAGAUGCAgCGAUU    1.9％

9488    4521    UGGGaGUGCAaAUGCAgCG    0.2％    9539    4526    GaGUGCAaAUGCAgCGAUU    0.2％

4522    4522    ACCUCUGACUAAGGGGAUU    91.3％   4527    4527    GUGGAUUCUUGAUCGUCUU    90.8％

9489    4522    ACCUCUGACUAgGGGGAUU    0.1％    9540    4527    GUGGAUUuUUGAUCGUCUU    0.7％

9490    4522    ACCUCUaACUAAGGGGAUU    0.7％    9541    4527    aUGGAUUCUUGAUCGUCUU    0.3％

9491    4522    ACCUCUGACaAAGGGGAUU    0.4％    9542    4527    GUGGAUcCUUGAUCGUCUU    0.1％

9492    4522    ACCUCUGACcAAGGGGAUU    0.2％    9543    4527    GUGGAUUCUUaAUCGUCUU    0.3％

9493    4522    ACCUCUGACUAAaGGGAUU    2.0％    9544    4527    GUGGAUUCUUGAUCaUCUU    0.2％

9494    4522    ACCUCUGACUAAGGGaAUU    3.0％    9545    4527    GUGGAUUCUUGAUCGcCUU    1.0％

9495    4522    ACCUCUGACUAAGGGGAUc    1.9％    9546    4527    GUGGAUUgUUGAUCGUCUU    0.1％

9496    4522    ACCUCUGACUAAGGGuAUU    0.1％    9547    4527    GUGGAUUaUUGAUCGcCUU    5.6％

9497    4522    ACCUCUuACUAAGGGGAUU    0.1％    9548    4527    GUGGAUUaUUGAUCGgCUU    1.0％

9498    4522    ACCUCUaACUAAGGGGAUc    0.2％    4528    4528    GGUGCAGAUGCAACGAUUC    90.8％

9499    4522    ACCUCUGACcAAGGGaAUU    0.1％    9549    4528    GGUGCAGAUGCAACGgUUC    0.5％

4523    4523    UGGAUUCUUGAUCGUCUUU    91.1％   9550    4528    GGUGCAGAUGCAgCGAUUC    1.5％

9500    4523    UGGAUUuUUGAUCGUCUUU    0.7％    9551    4528    GGUGCAGgUGCAACGAUUC    0.1％

9501    4523    UGGAUcCUUGAUCGUCUUU    0.1％    9552    4528    aGUGCAGAUGCAACGAUUC    1.0％

9502    4523    UGGAUUCUUaAUCGUCUUU    0.3％    9553    4528    GGUGCAaAUGCAACGAUUC    0.3％

9503    4523    UGGAUUCUUGAUCaUCUUU    0.2％    9554    4528    aGUGCAGAUGCAACGgUUC    1.3％

9504    4523    UGGAUUCUUGAUCGcCUUU    1.0％    9555    4528    aGUGCAGAUGCAgCGAUUC    1.6％

9505    4523    UGGAUUgUUGAUCGUCUUU    0.1％    9556    4528    aGUGCAGAUGCAgCGgUUC    0.2％

9506    4523    UGGAUUaUUGAUCGcCUUU    5.6％    9557    4528    aGUaCAGAUGCAACGAUUC    0.1％

9507    4523    UGGAUUaUUGAUCGgCUUU    1.0％    9558    4528    aGUGCAaAUGCAACGAUUC    0.1％

4524    4524    GGAUUCUUGAUCGUCUUUU    91.1％   9559    4528    aGUaCAGAUGCAgCGAUUC    1.9％

9508    4524    GGAUUuUUGAUCGUCUUUU    0.7％    9560    4528    aGUGCAaAUGCAgCGAUUC    0.2％

4529    4529    GGGGGUGCAGAUGCAACGA    90.8％   9612    4533    UCUUCUUGAAAAaUUGCAG    0.1％

9561    4529    GGGGGUGCAGAUGCAACGg    0.5％    9613    4533    UCUUCUUGAAAAcUUGCAG    0.5％

9562    4529    GGGGGUGCAGAUGCAgCGA    1.5％    9614    4533    UCUUCUUGAAAAUUUaCAG    0.8％

9563    4529    GGGGGUGCAGgUGCAACGA    0.1％    9615    4533    UCUcaUUGAAAAUUUGCAG    0.2％

9564    4529    GGGaGUGCAGAUGCAACGA    1.0％    9616    4533    UCUcCUUGAuAAUUUGCAG    0.1％

9565    4529    GGGGGUGCAaAUGCAACGA    0.3％    4534    4534    AUGGCUAAAGACAAGACCA    90.5％

9566    4529    GGGaGUGCAGAUGCAACGg    1.3％    9617    4534    AUGGCUAAAGACAAGACCg    3.0％

9567    4529    GGGaGUGCAGAUGCAgCGA    1.6％    9618    4534    AUGGCUAAAGACAAGgCCA    0.4％

9568    4529    GGGaGUGCAGAUGCAgCGg    0.2％    9619    4534    AUGGCUgAAGACAAGACCA    0.1％

9569    4529    GGGaGUaCAGAUGCAACGA    0.1％    9620    4534    gUGGCUAAAGACAAGACCA    4.9％

9570    4529    GGGaGUGCAaAUGCAACGA    0.1％    9621    4534    AUGGuUAAAGACAAGACCg    0.1％

9571    4529    GGGaGUaCAGAUGCAgCGA    1.9％    9622    4534    gUGGCUAAAGACAAGACCg    0.51％

9572    4529    GGGaGUGCAaAUGCAgCGA    0.2％    9623    4534    AUGGCUAAAGACAAaACCA    0.2％

4530    4530    CUCUGACUAAGGGGAUUUU    90.7％   9624    4534    AUGGCUAAAGACAAGACCc    0.1％

9573    4530    CUCUGACUAgGGGGAUUUU    0.1％    9625    4534    AUGGCUAAAGACAAGACCu    0.1％

9574    4530    CUCUaACUAAGGGGAUUUU    0.7％    9626    4534    AUGGCUAAAGACuAGACCu    0.2％

9575    4530    CUCUGACaAAGGGGAUUUU    0.4％    4535    4535    AUCUUCUUGAAAAUUUGCA    90.51％

9576    4530    CUCUGACcAAGGGGAUUUU    0.2％    9627    4535    AUCUUuUUGAAAAUUUGCA    0.1％

9577    4530    CUCUGACUAAaGGGAUUUU    2.0％    9628    4535    AcCUUCUUGAAAAUUUGCA    0.1％

9578    4530    CUCUGACUAAGGGaAUUUU    3.0％    9629    4535    AUCUcCUUGAAAAUUUGCA    5.9％

9579    4530    CUCUGACUAAGGGGAUcUU    0.5％    9630    4535    AUCUUaUUGAAAAUUUGCA    1.7％

9580    4530    CUCUGAC0AAGGGGAUUcU    0.6％    9631    4535    AUCUUCUcGAAAAUUUGCA    0.1％

9581    4530    CUCUGACUAAGGGuAUUUU    0.1％    9632    4535    AUCUUCUUGAAAAaUUGCA    0.1％

9582    4530    CUCUuACUAAGGGGAUUUU    0.1％    9633    4535    AUCUUCUUGAAAAcUUGCA    0.5％

9583    4530    CUCUGACcAAGGGaAUUUU    0.1％    9634    4535    AUCUUCUUGAAAAUUUaCA    0.8％

9584    4530    CUCUGACUAAGGGGAUccU    1.4％    9635    4535    AUCUcaUUGAAAAUUUGCA    0.2％

4531    4531    CCUCUGACUAAGGGGAUUU    90.7％   9636    4535    AUCUcCUUGAuAAUUUGCA    0.1％

9585    4531    CCUCUGACUAgGGGGAUUU    0.1％    4536    4536    GAAUGGGGGUGCAGAUGCA    90.4％

9586    4531    CCUCUaACUAAGGGGAUUU    0.7％    9637    4536    GAAUGGGGGUGCAGgUGCA    0.1％

9587    4531    CCUCUGACaAAGGGGAUUU    0.4％    9638    4536    GgAUGGGGGUGCAGAUGCA    2.4％

9588    4531    CCUCUGACcAAGGGGAUUU    0.2％    9639    4536    GAAUGGGaGUGCAGAUGCA    3.9％

9589    4531    CCUCUGACUAAaGGGAUUU    2.0％    9640    4536    GAAUGGGGGUGCAaAUGCA    0.3％

9590    4531    CCUCUGACUAAGGGaAUUU    3.0％    9641    4536    GgAUGGGaGUGCAGAUGCA    0.2％

9591    4531    CCUCUGACUAAGGGGAUcU    0.5％    9642    4536    GAAUGGGaGUaCAGAUGCA    2.0％

9592    4531    CCUCUGACUAAGGGGAUUc    0.6％    9643    4536    GgAUGGGaGUGCAaAUGCA    0.5％

9593    4531    CCUCUGACUAAGGGuAUUU    0.1％    4537    4537    CGAAUGGGGGUGCAGAUGC    90.2％

9594    4531    CCUCUuACUAAGGGGAUUU    0.1％    9644    4537    CGAAUGGGGGUGCAGgUGC    0.1％

9595    4531    CCUCUGACcAAGGGaAUUU    0.1％    9645    4537    CGgAUGGGGGUGCAGAUGC    2.4％

9596    4531    CCUCUGACUAAGGGGAUcc    1.4％    9646    4537    aGAAUGGGGGUGCAGAUGC    0.2％

4532    4532    UGUGGAUUCUUGAUCGUCU    90.7％   9647    4537    CGAAUGGGaGUGCAGAUGC    3.9％

9597    4532    UGUGGAUUuUUGAUCGUCU    0.7％    9648    4537    CGAAUGGGGGUGCAaAUGC    0.3％

9598    4532    cGUGGAUUCUUGAUCGUCU    0.1％    9649    4537    CGgAUGGGaGUGCAGAUGC    0.2％

9599    4532    UaUGGAUUCUUGAUCGUCU    0.3％    9650    4537    CGAAUGGGaGUaCAGAUGC    2.0％

9600    4532    UGUGGAUcCUUGAUCGUCU    0.1％    9651    4537    CGgAUGGGaGUGCAaAUGC    0.5％

9601    4532    UGUGGAUUCUUaAUCGUCU    0.3％    4538    4538    AAUGGGGGUGCAGAUGCAA    90.2％

9602    4532    UGUGGAUUCUUGAUCaUCU    0.2％    9652    4538    AAUGGGGGUGCAGAUGCAg    0.2％

9603    4532    UGUGGAUUCUUGAUCGcCU    1.0％    9653    4538    AAUGGGGGUGCAGgUGCAA    0.1％

9604    4532    UGUGGAUUgUUGAUCGUCU    0.1％    9654    4538    gAUGGGGGUGCAGAUGCAA    1.1％

9605    4532    UGUGGAUUaUUGAUCGcCU    5.6％    9655    4538    gAUGGGGGUGCAGAUGCAg    1.3％

9606    4532    UGUGGAUUaUUGAUCGgCU    1.0％    9656    4538    AAUGGGaGUGCAGAUGCAA    2.3％

4533    4533    UCUUCUUGAAAAUUUGCAG    90.5％   9657    4538    AAUGGGGGUGCAaAUGCAA    0.3％

9607    4533    UCUUuUUGAAAAUUUGCAG    0.1％    9658    4538    AAUGGGaGUGCAGAUGCAg    1.6％

9608    4533    cCUUCUUGAAAAUUUGCAG    0.1％    9659    4538    gAUGGGaGUGCAGAUGCAg    0.2％

9609    4533    UCUcCUUGAAAAUUUGCAG    5.9％    9660    4538    AAUGGGaGUaCAGAUGCAA    0.1％

9610    4533    UCUUaUUGAAAAUUUGCAG    1.7％    9661    4538    AAUGGGaGUaCAGAUGCAg    1.9％

9611    4533    UCUUCUcGAAAAUUUGCAG    0.1％    9662    4538    gAUGGGaGUGCAaAUGCAA    0.1％

表20-6.从表1-8所列甲型流感片段8(NS1&NS2)序列得到的保守和小变体19-mer序列。保守序列匹配所列病毒序列的至少89％，变体含有从参考序列的3个或更少核苷酸变化。

Seq    Ref                      ％总数    9703  5026  AUGGAAUGAUAAnACAGUU  0.1％

ID     ID   匹配序列                      9704  5026  AUGGAgUGAUAACACuGUU  0.1％

5021  502U  AUAACACAGUUCGAGUCUC  98.2％   5027  5027  AAUGGAAUGAUAACACAGU  97.9％

9663  5021  gUAACACgGUUCGAGUCUC  0.4％    9705  5027  AAUGGAgUGAUAACACAGU  0.1％

9664  5021  AUAACACAGcUCGAGUCUC  0.1％    9706  5027  AgUGGAAUGAUAACACAGU  0.2％

9665  5021  AUAACACAGUUaGAGUCUC  0.1％    9707  5027  AAUGGAAUGgUAACACgGU  0.4％

9666  5021  AUAACACAGUUCaAGUCUC  0.2％    9708  5027  AAUGGAAUaAUAACACAGU  1.1％

9667  5021  AUAACACAGUUCGAGUCaC  0.6％    9709  5027  AAUGGAAUGAUAACACAGc  0.1％

9668  5021  AUAACACuGUUCGAGUCUC  0.1％    9710  5027  AAUGGAAUGAUAAnACAGU  0.1％

9669  5021  AUAAnACAGUUCGAGUCUC  0.1％    9711  5027  AAUGGAgUGAUAACACUGU  0.1％

9670  5021  AUAACACAGUUCaAGUCaC  0.2％    5028  5028  UUGAAUGGAAUGAUAACAC  97.8％

5022  5022  UAACACAGUUCGAGUCUCU  98.2％   9712  5028  UUGAAUGGAAUGgUAACAC  0.4％

9671  5022  UAACACgGUUCGAGUCUCU  0.4％    9713  5028  UUGAAUGGAgUGAUAACAC  0.2％

9672  5022  UAACACAGcUCGAGUCUCU  0.1％    9714  5028  UUGAgUGGAAUGAUAACAC  0.2％

9673  5022  UAACACAGUUaGAGUCUCU  0.1％    9715  5028  nUGAAUGGAAUGAUAACAC  0.2％

9674  5022  UAACACAGUUCaAGUCUCU  0.2％    9716  5028  UUGAAUGGAAUaAUAACAC  1.1％

9675  5022  UAACACAGUUCGAGUCaCU  0.6％    9717  5028  UUGAAUGGAAUGAUAAnAC  0.1％

9676  5022  UAACACuGUUCGAGUCUCU  0.1％    5029  5029  UGAUAACACAGUUCGAGUC  97.7％

9677  5022  UAAnACAGUUCGAGUCUCU  0.1％    9718  5029  UGgUAACACgGUUCGAGUC  0.4％

9678  5022  UAACACAGUUCaAGUCaCU  0.2％    9719  5029  UaAUAACACAGUUCGAGUC  1.1％

5023  5023  UGAAUGGAAUGAUAACACA  98.0％   9720  5029  UGAUAACACAGcUCGAGUC  0.1％

9679  5023  UGAAUGGAgUGAUAACACA  0.1％    9721  5029  UGAUAACACAGUUaGAGUC  0.1％

9680  5023  UGAgUGGAAUGAUAACACA  0.2％    9722  5029  UGAUAACACAGUUCaAGUC  0.4％

9681  5023  UGAAUGGAAUGgUAACACg  0.4％    9723  5029  UGAUAACACuGUUCGAGUC  0.1％

9682  5023  UGAAUGGAAUaAUAACACA  1.1％    9724  5029  UGAUAAnACAGUUCGAGUC  0.1％

9683  5023  UGAAUGGAAUGAUAAnACA  0.1％    5030  5030  AUGAUAACACAGUUCGAGU  97.6％

9684  5023  UGAAUGGAgUGAUAACACu  0.1％    9725  5030  gUGAUAACACAGUUCGAGU  0.1％

5024  5024  GAAUGGAAUGAUAACACAG  98.0％   9726  5030  AUGgUAACACgGUUCGAGU  0.4％

9685  5024  GAAUGGAgUGAUAACACAG  0.1％    9727  5030  AUaAUAACACAGUUCGAGU  1.1％

9686  5024  GAgUGGAAUGAUAACACAG  0.2％    9728  5030  AUGAUAACACAGcUCGAGU  0.1％

9687  5024  GAAUGGAAUGgUAACACgG  0.4％    9729  5030  AUGAUAACACAGUUaGAGU  0.1％

9688  5024  GAAUGGAAUaAUAACACAG  1.1％    9730  5030  AUGAUAACACAGUUCaAGU  0.4％

9689  5024  GAAUGGAAUGAUAAnACAG  0.1％    9731  5030  AUGAUAAnACAGUUCGAGU  0.1％

9690  5024  GAAUGGAgUGAUAACACuG  0.1％    9732  5030  gUGAUAACACuGUUCGAGU  0.1％

5025  5025  UGGAAUGAUAACACAGUUC  98.0％   5031  5031  GGAAUGAUAACACAGUUCG  97.6％

9691  5025  UGGAgUGAUAACACAGUUC  0.1％    9733  5031  GGAgUGAUAACACAGUUCG  0.1％

9692  5025  UGGAAUGgUAACACgGUUC  0.4％    9734  5031  GGAAUGgUAACACgGUUCG  0.4％

9693  5025  UGGAAUaAUAACACAGUUC  1.1％    9735  5031  GGAAUaAUAACACAGUUCG  1.1％

9694  5025  UGGAAUGAUAACACAGcUC  0.1％    9736  5031  GGAAUGAUAACACAGcUCG  0.1％

9695  5025  UGGAAUGAUAACACAGUUa  0.1％    9737  5031  GGAAUGAUAACACAGUUaG  0.1％

9696  5025  UGGAAUGAUAAnACAGUUC  0.1％    9738  5031  GGAAUGAUAACACAGUUCa  0.4％

9697  5025  UGGAgUGAUAACACuGUUC  0.1％    9739  5031  GGAAUGAUAAnACAGUUCG  0.1％

5026  5026  AUGGAAUGAUAACACAGUU  97.9％   9740  5031  GGAgUGAUAACACuGUUCG  0.1％

9698  5026  AUGGAgUGAUAACACAGUU  0.1％    5032  5032  GAAUGAUAACACAGUUCGA  97.6％

9699  5026  gUGGAAUGAUAACACAGUU  0.2％    9741  5032  GAgUGAUAACACAGUUCGA  0.1％

9700  5026  AUGGAAUGgUAACACgGUU  0.4％    9742  5032  GAAUGgUAACACgGUUCGA  0.4％

9701  5026  AUGGAAUaAUAACACAGUU  1.1％    9743  5032  GAAUaAUAACACAGUUCGA  1.1％

9702  5026  AUGGAAUGAUAACACAGcU  0.1％    9744  5032  GAAUGAUAACACAGcUCGA  0.1％

9745    5032    GAAUGAUAACACAGUUaGA    0.1％    9792    5039    GAGaAUGUCAAAAAUGCAA    0.1％

9746    5032    GAAUGAUAACACAGUUCaA    0.4％    9793    5039    GAGGAUGUCAAAAuUGCAA    0.5％

9747    5032    GAAUGAUAAnACAGUUCGA    0.1％    5040    5040    GAUGUCAAAAAUGCAAUUG    96.8％

9748    5032    GAgUGAUAACACuGUUCGA    0.1％    9794    5040    GAUGUCAAAAAUGCAgUUG    1.5％

5033    5033    AAUGAUAACACAGUUCGAG    97.6％   9795    5040    GAUGUCAAAAAUGCgAUUG    1.0％

9749    5033    AgUGAUAACACAGUUCGAG    0.1％    9796    5040    GAUGUCAAAgAUGCAAUUG    0.1％

9750    5033    AAUGgUAACACgGUUCGAG    0.4％    9797    5040    aAUGUCAAAAAUGCAAUUG    0.1％

9751    5033    AAUaAUAACACAGUUCGAG    1.1％    9798    5040    GAUGUCAAAAAUGCAAUUa    0.1％

9752    5033    AAUGAUAACACAGcUCGAG    0.1％    9799    5040    GAUGUCAAAAuUGCAAUUG    0.5％

9753    5033    AAUGAUAACACAGUUaGAG    0.1％    5041    5041    UGAGGAUGUCAAAAAUGCA    96.4％

9754    5033    AAUGAUAACACAGUUCaAG    0.4％    9800    5041    UGAGGAUGUCAAAAAUGCg    1.0％

9755    5033    AAUGAUAAnACAGUUCGAG    0.1％    9801    5041    UGAGGAUGUCAAAgAUGCA    0.1％

9756    5033    AgUGAUAACACuGUUCGAG    0.1％    9802    5041    aGAGGAUGUCAAAAAUGCA    1.5％

5034    5034    CUUGAAUGGAAUGAUAACA    97.5％   9803    5041    cGAGGAUGUCAAAAAUGCA    0.4％

9757    5034    CUUGAAUGGAAUGgUAACA    0.4％    9804    5041    UaAGGAUGUCAAAAAUGCA    0.1％

9758    5034    CUUGAAUGGAgUGAUAACA    0.2％    9805    5041    UGAGaAUGUCAAAAAUGCA    0.1％

9759    5034    CUUGAgUGGAAUGAUAACA    0.2％    9806    5041    UGAGGAUGUCAAAAuUGCA    0.5％

9760    5034    uUUGAAUGGAAUGAUAACA    0.3％    5042    5042    CGGCUUCGCCGAGAUCAGA    96.2％

9761    5034    CUUGAAUGGAAUaAUAACA    1.1％    9807    5042    CGGCUUCGCCGgGAUCAGA    0.5％

9762    5034    CUUGAAUGGAAUGAUAAnA    0.1％    9808    5042    aGGCUUCGCCGAGAUCAGA    0.1％

9763    5034    nnUGAAUGGAAUGAUAACA    0.2％    9809    5042    CGaCUUCGCCGAGAUCAGA    0.8％

5035    5035    GAUAACACAGUUCGAGUCU    97.1％   9810    5042    CGGaUUCGCCGAGAUCAGA    0.1％

9764    5035    Gg0AACACgGUUCGAGUCU    0.4％    9811    5042    CGGCUcCGCCGAGAUCAGA    0.3％

9765    5035    aAUAACACAGUUCGAGUCU    1.1％    9812    5042    CGGCUUCaCCGAGAUCAGA    0.1％

9766    5035    GA0AACACAGCUCGAGUCU    0.1％    9813    5042    CGGCUUCGCaGAGAUCAGA    0.1％

9767    5035    GAUAACACAGUUaGAGUCU    0.1％    9814    5042    CGGCUUCGCCGAGAcCAGA    0.3％

9768    5035    GAUAACACAGUUCaAGUCU    0.2％    9815    5042    CGGCUUCGCCGAGAUaAGA    0.1％

9769    5035    GAUAACACAGUUCGAGUCa    0.6％    9816    5042    CGGCUUCGCCGAGAUCAaA    0.4％

9770    5035    GAUAACACuGUUCGAGUCU    0.1％    9817    5042    CGGCUUCGCCGAuAUCAGA    0.2％

9771    5035    GAUAAnACAGUUCGAGUCU    0.1％    9818    5042    CGGgUUuGCCGAGAUCAGA    0.1％

9772    5035    GAUAACACAGUUCaAGUCa    0.2％    9819    5042    aGaCUUCGCCGAGAUCAGA    0.1％

5036    5036    AUGUCAAAAAUGCAAUUGG    96.9％   9820    5042    CGaCUUCGCaGAGAUCAGA    0.1％

9773    5036    AUGUCAAAAAUGCAgUUGG    1.5％    9821    5042    CGGCUcCGCCGAGAUCAaA    0.3％

9774    5036    AUGUCAAAAAUGCgAUUGG    1.0％    9822    5042    CGGCUUCGCCGAnnUCAGA    0.1％

9775    5036    AUGUCAAAgAUGCAAUUGG    0.1％    5043    5043    UGUCAAAAAUGCAAUUGGG    95.6％

9776    5036    AUGUCAAAAAUGCAAUUaG    0.1％    9823    5043    UGUCAAAAAUGCAgUUGGG    1.0％

9777    5036    AUGUCAAAAuUGCAAUUGG    0.5％    9824    5043    UGUCAAAAAUGCgAUUGGG    1.0％

5037    5037    GGAUGUCAAAAAUGCAAUU    96.9％   9825    5043    UGUCAAAgAUGCAAUUGGG    0.1％

9778    5037    GGAUGUCAAAAAUGCAgUU    1.5％    9826    5043    UGUCAAAAAUGCAAUUaGG    0.1％

9779    5037    GGAUGUCAAAAAUGCgAUU    1.0％    9827    5043    UGUCAAAAAUGCAAUUGGa    0.1％

9780    5037    GGAUGUCAAAgAUGCAAUU    0.1％    9828    5043    UGUCAAAAAUGCAAUUGGc    1.2％

9781    5037    GaAUGUCAAAAAUGCAAUU    0.1％    9829    5043    UGUCAAAAuUGCAAUUGGG    0.5％

9782    5037    GGAUGUCAAAAuUGCAAUU    0.5％    9830    5043    UGUCAAAAAUGCAgUUGGa    0.5％

5038    5038    AGGAUGUCAAAAAUGCAAU    96.9％   5044    5044    UCUACAGAGAUUCGCUUGG    95.5％

9783    5038    AGGAUGUCAAAAAUGCAgU    1.5％    9831    5044    UCUACAGAGAUUuGCUUGG    0.2％

9784    5038    AGGAUGUCAAAAAUGCgAU    1.0％    9832    5044    UaUACAGAGAUUCGCUUGG    1.3％

9785    5038    AGGAUGUCAAAgAUGCAAU    0.1％    9833    5044    UCUACAGAaAUUCGCUUGG    0.1％

9786    5038    AGaAUGUCAAAAAUGCAAU    0.1％    9834    5044    UCUACAGAGAUUCaCUUGG    2.6％

9787    5038    AGGAUGUCAAAAuUGCAAU    0.5％    9835    5044    UCUACAGAGAUUCGCUUGa    0.2％

5039    5039    GAGGAUGUCAAAAAUGCAA    96.8％   9836    5044    UCUACAGAGAUUCGCUUnG    0.1％

9788    5039    GAGGAUGUCAAAAAUGCAg    1.5％    9837    5044    UCUACAGAGAUUCuCUUGG    0.1％

9789    5039    GAGGAUGUCAAAAAUGCgA    1.0％    5045    5045    GCAAUUGGGGUCCUCAUCG    94.8％

9790    5039    GAGGAUGUCAAAgAUGCAA    0.1％    9838    5045    GCAAUUGGGGUCCUCgUCG    0.1％

9791    5039    aAGGAUGUCAAAAAUGCAA    0.1％    9839    5045    GCAAUUGGGGUuCUCAUCG    0.1％

9840    5045    GCAgUUGGGGUCCUCAUCG    1.0％    9889    5050    AAAAAUGCAAUUGGGGUuC    0.1％

9841    5045    GCgAUUGGGGUCCUCAUCG    1.0％    9890    5050    AAAAAUGCAgUUGGGGUCC    1.0％

9842    5045    GCAAUUaGGGUCCUCAUCG    0.1％    9891    5050    AAAAAUGCgAUUGGGGUCC    1.0％

9843    5045    GCAAUUGGaGUCCUCAUCG    0.1％    9892    5050    AAAgAUGCAAUUGGGGUCC    0.1％

9844    5045    GCAAUUGGcGUCCUCAUCG    1.2％    9893    5050    AAAAAUGCAAUUaGGGUCC    0.1％

9845    5045    GCAAUUGGGaUCCUCAUCG    1.0％    9894    5050    AAAAAUGCAAUUGGaGUCC    0.1％

9846    5045    GCAAUUGGGcUCCUCAUCG    0.1％    9895    5050    AAAAAUGCAAUUGGcGUCC    1.2％

9847    5045    GCAgUUGGaGUCCUCAUCG    0.5％    9896    5050    AAAAAUGCAAUUGGGaUCC    1.1％

9848    5045    GCAAUUGGGaUCCUCAUCa    0.1％    9897    5050    AAAAAUGCAAUUGGGcUCC    0.1％

5046    5046    CAAUUGGGGUCCUCAUCGG    94.8％   9898    5050    AAAAuUGCAAUUGGGGUCC    0.5％

9849    5046    CAAUUGGGGUCCUCgUCGG    0.1％    9899    5050    AAAAAUGCAgUUGGaGUCC    0.5％

9850    5046    CAAUUGGGGUuCUCAUCGG    0.1％    5051    5051    AAAAUGCAAUUGGGGUCCU    94.3％

9851    5046    CAgUUGGGGUCCUCAUCGG    1.0％    9900    5051    AAAAUGCAAUUGGGGUuCU    0.1％

9852    5046    CgAUUGGGGUCCUCAUCGG    1.0％    9901    5051    AAAAUGCAgUUGGGGUCCU    1.0％

9853    5046    CAAUUaGGGUCCUCAUCGG    0.1％    9902    5051    AAAAUGCgAUUGGGGUCCU    1.0％

9854    5046    CAAUUGGaGUCCUCAUCGG    0.1％    9903    5051    AAgAUGCAAUUGGGGUCCU    0.1％

9855    5046    CAAUUGGcGUCCUCAUCGG    1.2％    9904    5051    AAAAUGCAAUUaGGGUCCU    0.1％

9856    5046    CAAUUGGGaUCCUCAUCGG    1.0％    9905    5051    AAAAUGCAAUUGGaGUCCU    0.1％

9857    5046    CAAUUGGGcUCCUCAUCGG    0.1％    9906    5051    AAAAUGCAAUUGGcGUCCU    1.2％

9858    5046    CAgUUGGaGUCCUCAUCGG    0.5％    9907    5051    AAAAUGCAAUUGGGaUCCU    1.1％

5047    5047    UGCAAUUGGGGUCCUCAUC    94.8％   9908    5051    AAAAUGCAAUUGGGcUCCU    0.1％

9859    5047    UGCAAUUGGGGUCCUCgUC    0.1％    9909    5051    AAAuUGCAAUUGGGGUCCU    0.5％

9860    5047    UGCAAUUGGGGUuCUCAUC    0.1％    9910    5051    AAAAUGCAgUUGGaGUCCU    0.5％

9861    5047    UGCAgUUGGGGUCCUCAUC    1.0％    5052    5052    AUGCAAUUGGGGUCCUCAU    94.3％

9862    5047    UGCgAUUGGGGUCCUCAUC    1.0％    9911    5052    AUGCAAUUGGGGUCCUCgU    0.1％

9863    5047    UGCAAUUaGGGUCCUCAUC    0.1％    9912    5052    AUGCAAUUGGGGUuCUCAU    0.1％

9864    5047    UGCAAUUGGaGUCCUCAUC    0.1％    9913    5052    AUGCAgUUGGGGUCCUCAU    1.0％

9865    5047    UGCAAUUGGcGUCCUCAUC    1.2％    9914    5052    AUGCgAUUGGGGUCCUCAU    1.0％

9866    5047    UGCAAUUGGGaUCCUCAUC    1.1％    9915    5052    AUGCAAUUaGGGUCCUCAU    0.1％

9867    5047    UGCAAUUGGGcUCCUCAUC    0.1％    9916    5052    AUGCAAUUGGaGUCCUCAU    0.1％

9868    5047    UGCAgUUGGaGUCCUCAUC    0.5％    9917    5052    AUGCAAUUGGcGUCCUCAU    1.2％

5048    5048    UCAAAAAUGCAAUUGGGGU    94.4％   9918    5052    AUGCAAUUGGGaUCCUCAU    1.1％

9869    5048    UCAAAAAUGCAgUUGGGGU    1.0％    9919    5052    AUGCAAUUGGGcUCCUCAU    0.1％

9870    5048    UCAAAAAUGCgAUUGGGGU    1.0％    9920    5052    uUGCAAUUGGGGUCCUCAU    0.5％

9871    5048    UCAAAgAUGCAAUUGGGGU    0.1％    9921    5052    AUGCAgUUGGaGUCCUCAU    0.5％

9872    5048    UCAAAAAUGCAAUUaGGGU    0.1％    5053    5053    CAAAAAUGCAAUUGGGGUC    94.3％

9873    5048    UCAAAAAUGCAAUUGGaGU    0.1％    9922    5053    CAAAAAUGCAAUUGGGGUu    0.1％

9874    5048    UCAAAAAUGCAAUUGGcGU    1.2％    9923    5053    CAAAAAUGCAgUUGGGGUC    1.0％

9875    5048    UCAAAAAUGCAAUUGGGaU    1.1％    9924    5053    CAAAAAUGCgAUUGGGGUC    1.0％

9876    5048    UCAAAAAUGCAAUUGGGcU    0.1％    9925    5053    CAAAgAUGCAAUUGGGGUC    0.1％

9877    5048    UCAAAAuUGCAAUUGGGGU    0.5％    9926    5053    CAAAAAUGCAAUUaGGGUC    0.1％

9878    5048    UCAAAAAUGCAgUUGGaGU    0.5％    9927    5053    CAAAAAUGCAAUUGGaGUC    0.1％

5049    5049    GUCAAAAAUGCAAUUGGGG    94.4％   9928    5053    CAAAAAUGCAAUUGGcGUC    1.2％

9879    5049    GUCAAAAAUGCAgUUGGGG    1.0％    9929    5053    CAAAAAUGCAAUUGGGaUC    1.1％

9880    5049    GUCAAAAAUGCgAUUGGGG    1.0％    9930    5053    CAAAAAUGCAAUUGGGcUC    0.1％

9881    5049    GUCAAAgAUGCAAUUGGGG    0.1％    9931    5053    CAAAAuUGCAAUUGGGGUC    0.5％

9882    5049    GUCAAAAAUGCAAUUaGGG    0.1％    9932    5053    CAAAAAUGCAgUUGGaGUC    0.5％

9883    5049    GUCAAAAAU  AAUUGGaG    0.1％    5054    5054    AAAUGCAAUUGGGGUCCUC    94.3％

9884    5049    GUCAAAAAUGCAAUUGGcG    1.2％    9933    5054    AAAUGCAAUUGGGGUuCUC    0.1％

9885    5049    GUCAAAAAUGCAAUUGGGa    1.1％    9934    5054    AAAUGCAgUUGGGGUCCUC    1.0％

9886    5049    GUCAAAAAUGCAAUUGGGc    0.1％    9935    5054    AAAUGCgAUUGGGGUCCUC    1.0％

9887    5049    GUCAAAAuUGCAAUUGGGG    0.5％    9936    5054    AgAUGCAAUUGGGGUCCUC    0.1％

9888    5049    GUCAAAAAUGCAgUUGGaG    0.5％    9937    5054    AAAUGCAAUUaGGGUCCUC    0.1％

5050    5050    AAAAAUGCAAUUGGGGUCC    94.3％   9938    5054    AAAUGCAAUUGGaGUCCUC    0.1％

9939    5054    AAAUGCAAUUGGcGUCCUC    1.2％    9989    5058    CUUGAUCGGaUUCGCCGAG    0.1％

9940    5054    AAAUGCAAUUGGGaUCCUC    1.1％    9990    5058    CUUGAUCGGCUcCGCCGAG    0.7％

9941    5054    AAAUGCAAUUGGGcUCCUC    0.1％    9991    5058    CUUGAUCGGCUUCaCCGAG    0.1％

9942    5054    AAuUGCAAUUGGGGUCCUC    0.5％    9992    5058    CUUGAUCGGCUUCGCaGAG    0.1％

9943    5054    AAAUGCAgUUGGaGUCCUC    0.5％    9992    5058    CUUGAUCGGCUUCGCCGAn    0.1％

5055    5055    AAUGCAAUUGGGGUCCUCA    94.2％   9994    5058    CUUGAUCGGCUUCGCCGAu    0.2％

9944    5055    AAUGCAAUUGGGGUCCUCg    0.1％    9995    5058    CUUGAUaGaCUUCGCCGAG    0.1％

9945    5055    AAUGCAAUUGGGGUuCUCA    0.1％    9996    5058    CUUGAUCGaCUUCGCaGAG    0.1％

9946    5055    AAUGCAgUUGGGGUCCUCA    1.0％    9997    5058    CUaGAcCGGCUUCGCCGgG    0.2％

9947    5055    AAUGCgAUUGGGGUCCUCA    1.0％    9998    5058    CUUGAcCGGgUUuGCCGAG    0.1％

9948    5055    gAUGCAAUUGGGGUCCUCA    0.1％    5059    5059    GAAAGCGAAUUUCAGUGUG    93.6％

9949    5055    AAUGCAAUUaGGGUCCUCA    0.1％    9999    5059    GAAgGCGAAUUUCAGUGUG    0.1％

9950    5055    AAUGCAAUUGGaGUCCUCA    0.1％    10000   5059    GAgAGCGAAUUUCAGUGUG    0.1％

9951    5055    AAUGCAAUUGGcGUCCUCA    1.2％    10001   5059    aAAAGCGAAUUUCAGUGUG    0.2％

9952    5055    AAUGCAAUUGGGaUCCUCA    1.1％    10002   5059    GAAAGCaAAUUUCAGUGUG    0.3％

9953    5055    AAUGCAAUUGGGcUCCUCA    0.1％    10003   5059    GAAAGCGAAcUUCAGUGUG    1.3％

9954    5055    AuUGCAAUUGGGGUCCUCA    0.5％    10004   5059    GAAAGCGAAUaUCAGUGUG    0.1％

9955    5055    AAUGCAgUUGGaGUCCUCA    0.5％    10005   5059    GAAAGCGAAUUUCAGcGUG    0.2％

5056    5056    UGAAAGCGAAUUUCAGUGU    93.8％   10006   5059    GAAAGCGAAUUUCAGUGUa    0.2％

9956    5056    UGAAgGCGAAUUUCAGUGU    0.1％    10007   5059    GAAAGCuAAUUUCAGUGUG    0.4％

9957    5056    UGAgAGCGAAUUUCAGUGU    0.1％    10008   5059    uAAAGCGAAUUUCAGUGUG    0.1％

9958    5056    UaAAAGCGAAUUUCAGUGU    0.2％    10009   5059    aAAAGCGAAcUUCAGUGUG    0.3％

9959    5056    UGAAAGCaAAUUUCAGUGU    0.3％    10010   5059    GAAAGCaAAcUUCAGUGUG    0.9％

9960    5056    UGAAAGCGAAcUUCAGUGU    1.3％    10011   5059    GAAAGCaAAcUUuAGUGUG    2.2％

9961    5056    UGAAAGCGAAUaUCAGUGU    0.1％    5060    5060    AUCGGCUUCGCCGAGAUCA    93.4％

9962    5056    UGAAAGCGAAUUUCAGcGU    0.2％    10012   5060    AUCGGCUUCGCCGgGAUCA    0.3％

9963    5056    UGAAAGCuAAUUUCAGUGU    0.4％    10013   5060    AcCGGCUUCGCCGAGAUCA    3.1％

9964    5056    UuAAAGCGAAUUUCAGUGU    0.1％    10014   5060    AUaGGCUUCGCCGAGAUCA    0.1％

9965    5056    UaAAAGCGAAcUUCAGUGU    0.3％    10015   5060    AUCGaCUUCGCCGAGAUCA    0.8％

9966    5056    UGAAAGCaAAcUUCAGUGU    0.9％    10016   5060    AUCGGaUUCGCCGAGAUCA    0.1％

9967    5056    UGAAAGCaAAcUUuAGUGU    2.2％    10017   5060    AUCGGCUcCGCCGAGAUCA    0.6％

5057    5057    UUGAUCGGCUUCGCCGAGA    93.7％   10018   5060    AUCGGCUUCaCCGAGAUCA    0.1％

9968    5057    UUGAUCGGCUUCGCCGgGA    0.3％    10019   5060    AUCGGCUUCGCaGAGAUCA    0.1％

9969    5057    UcGAUCGGCUUCGCCGAGA    0.1％    10020   5060    AUCGGCUUCGCCGAGAcCA    0.3％

9970    5057    UUGAcCGGCUUCGCCGAGA    3.1％    10021   5060    AUCGGCUUCGCCGAGAUaA    0.1％

9971    5057    UUGAUaGGCUUCGCCGAGA    0.1％    10022   5060    AUCGGCUUCGCCGAuAUCA    0.2％

9972    5057    UUGAUCGaCUUCGCCGAGA    0.8％    10023   5060    AcCGGCUUCGCCGgGAUCA    0.2％

9973    5057    UUGAUCGGaUUCGCCGAGA    0.1％    10024   5060    AUaGaCUUCGCCGAGAUCA    0.1％

9974    5057    UUGAUCGGCUcCGCCGAGA    0.7％    10025   5060    AUCGaCUUCGCaGAGAUCA    0.1％

9975    5057    UUGAUCGGCUUCaCCGAGA    0.1％    10026   5060    AUCGGCUcCGCCGAGAUCu    0.1％

9976    5057    UUGAUCGGCUUCGCaGAGA    0.1％    10027   5060    AUCGGCUUCGCCGAnnUCA    0.1％

9977    5057    UUGAUCGGCUUCGCCGAuA    0.2％    10028   5060    AcCGGgUUuGCCGAGAUCA    0.1％

9978    5057    UUGAUaGaCUUCGCCGAGA    0.1％    5061    5061    GAUCGGCUUCGCCGAGAUC    93.4％

9979    5057    UUGAUCGaCUUCGCaGAGA    0.1％    10029   5061    GAUCGGCUUCGCCGgGAUC    0.3％

9980    5057    UUGAUCGGCUUCGCCGAnn    0.1％    10030   5061    GAcCGGCUUCGCCGAGAUC    3.1％

9981    5057    UaGAcCGGCUUCGCCGgGA    0.2％    10031   5061    GAUaGGCUUCGCCGAGAUC    0.1％

9982    5057    UUGAcCGGgUUuGCCGAGA    0.1％    10032   5061    GAUCGaCUUCGCCGAGAUC    0.8％

5058    5058    CUUGAUCGGCUUCGCCGAG    93.6％   10033   5061    GAUCGGaUUCGCCGAGAUC    0.1％

9983    5058    CUUGAUCGGCUUCGCCGgG    0.3％    10034   5061    GAUCGGCUcCGCCGAGAUC    0.7％

9984    5058    aUUGAUCGGCUUCGCCGAG    0.1％    10035   5061    GAUCGGCUUCaCCGAGAUC    0.1％

9985    5058    CUcGAUCGGCUUCGCCGAG    0.1％    10036   5061    GAUCGGCUUCGCaGAGAUC    0.1％

9986    5058    CUUGAcCGGCUUCGCCGAG    3.1％    10037   5061    GAUCGGCUUCGCCGAGAcC    0.3％

9987    5058    CUUGAUaGGCUUCGCCGAG    0.1％    10038   5061    GAUCGGCUUCGCCGAGAUa    0.1％

9988    5058    CUUGAUCGaCUUCGCCGAG    0.8％    10039   5061    GAUCGGCUUCGCCGAuAUC    0.2％

10040    5061  GAcCGGCUUCGCCGgGAUC    0.2％    10091    5064    GcGCAAUUGUUGGCGAAAU    0.6％

10041    5061  GAUaGaCUUCGCCGAGAUC    0.1％    10092    5064    GAaCAAUUGUUGGuGAAAU    0.1％

10042    5061  GAUCGaCUUCGCaGAGAUC    0.1％    10093    5064    GgaCAAUUGUUGGCGAAAU    0.2％

10043    5061  GAUCGGCUUCGCCGAnnUC    0.1％    10094    5064    GgGCAAUUGUaGGCGAAAU    0.1％

10044    5061  GAcCGGgUUuGCCGAGAUC    0.1％    10095    5064    GAcgAAUUGUUGGCGAAAU    0.1％

5062     5062  UGAUCGGCUUCGCCGAGAU    93.4％   10096    5064    GAGCAAUaGUgGGCGAAAU    1.6％

10045    5062  UGAUCGGCUUCGCCGgGAU    0.3％    10097    5064    GAGCAAUcGUUGGaGAAAU    0.3％

10046    5062  cGAUCGGCUUCGCCGAGAU    0.1％    10098    5064    GAGCAAUcGUUGGaGAgAU    0.1％

10047    5062  UGAcCGGCUUCGCCGAGAU    3.1％    5065     5065    GGAGCAAUUGUUGGCGAAA    92.8％

10048    5062  UGAUaGGCUUCGCCGAGAU    0.1％    10099    5065    GGAGCAAUUGUUGGuGAAA    0.1％

10049    5062  UGAUCGaCUUCGCCGAGAU    0.8％    10100    5065    GGAGCAgUUGUUGGCGAAA    0.2％

10050    5062  UGAUCGGaUUCGCCGAGAU    0.1％    10101    5065    GGAGuAAUUGUUGGCGAAA    0.7％

10051    5062  UGAUCGGCUcCGCCGAGAU    0.7％    10102    5065    GGgGCAAUUGUUGGCGAAA    0.7％

10052    5062  UGAUCGGCUUCaCCGAGAU    0.1％    10103    5065    GGgGCAAUUGUUGGCGAgA    0.1％

10053    5062  UGAUCGGCUUCGCaGAGAU    0.1％    10104    5065    GaAGCAAUUGUUGGCGAAA    0.1％

10054    5062  UGAUCGGCUUCGCCGAGAc    0.3％    10105    5065    GGAaCAAUUGUUGGCGAAA    0.3％

10055    5062  UGAUCGGCUUCGCCGAuAU    0.2％    10106    5065    GGAGCAAUUaUUGGCGAAA    0.1％

10056    5062  UGAUaGaCUUCGCCGAGAU    0.1％    10107    5065    GGAGCAAUUGUaGGCGAAA    0.1％

10057    5062  UGAUCGaCUUCGCaGAGAU    0.1％    10108    5065    GGAGCAAUUGUgGGCGAAA    0.1％

10058    5062  UGAUCGGCUUCGCCGAnnU    0.1％    10109    5065    GGAGCAAUUGUUGcCGAAA    0.1％

10059    5062  aGAcCGGCUUCGCCGgGAU    0.2％    10110    5065    GGcGCAAUUGUUGGCGAAA    0.6％

10060    5062  UGAcCGGgUUuGCCGAGAU    0.1％    10111    5065    GGAaCAAUUGUUGGuGAAA    0.1％

5063     5063  UCGGCUUCGCCGAGAUCAG    93.2％   10112    5065    GGgaCAAUUGUUGGCGAAA    0.2％

10061    5063  UCGGCUUCGCCGgGAUCAG    0.3％    10113    5065    GGgGCAAUUGUaGGCGAAA    0.1％

10062    5063  cCGGCUUCGCCGAGAUCAG    2.9％    10114    5065    GGAcgAAUUGUUGGCGAAA    0.1％

10063    5063  UaGGCUUCGCCGAGAUCAG    0.1％    10115    5065    GGAGCAAUaGUgGGCGAAA    1.6％

10064    5063  UCGaCUUCGCCGAGAUCAG    0.8％    10116    5065    GGAGCAAUcGUUGGaGAAA    0.3％

10065    5063  UCGGaUUCGCCGAGAUCAG    0.1％    10117    5065    GGAGCAAUcGUUGGaGAgA    0.1％

10066    5063  UCGGCUcCGCCGAGAUCAG    0.3％    5066     5066    UUCCUUGAUCGGCUUCGCC    92.7％

10067    5063  UCGGCUUCaCCGAGAUCAG    0.1％    10118    5066    UUuCUUGAUCGGCUUCGCC    1.5％

10068    5063  UCGGCUUCGCaGAGAUCAG    0.1％    10119    5066    UUCaUUGAUCGGCUUCGCC    0.1％

10069    5063  UCGGCUUCGCCGAGAcCAG    0.3％    10120    5066    UUCCUUGAcCGGCUUCGCC    3.1％

10070    5063  UCGGCUUCGCCGAGAUaAG    0.1％    10121    5066    UUCCUUGAUaGGCUUCGCC    0.1％

10071    5063  UCGGCUUCGCCGAGAUCAa    0.2％    10122    5066    UUCCUUGAUCGaCUUCGCC    0.8％

10072    5063  UCGGCUUCGCCGAuAUCAG    0.2％    10123    5066    UUCCUUGAUCGGaUUCGCC    0.1％

10073    5063  cCGGCUUCGCCGgGAUCAG    0.2％    10124    5066    UUCCUUGAUCGGCUcCGCC    0.7％

10074    5063  cCGGCUUCGCCGAGAUCAa    0.2％    10125    5066    UUCCUUGAUCGGCUUCaCC    0.1％

10075    5063  UaGaCUUCGCCGAGAUCAG    0.1％    10126    5066    UUCCUUGAUCGGCUUCGCa    0.1％

10076    5063  UCGaCUUCGCaGAGAUCAG    0.1％    10127    5066    UUuCUcGAUCGGCUUCGCC    0.1％

10077    5063  UCGGCUcCGCCGAGAUCAa    0.3％    10128    5066    UUCCUUGAUaGaCUUCGCC    0.1％

10078    5063  UCGGCUUCGCCGAnnUCAG    0.1％    10129    5066    UUCCUUGAcCGGgUUuGCC    0.1％

10079    5063  cCGGgUUuGCCGAGAUCAG    0.1％    10130    5066    UUuCUaGAcCGGCUUCGCC    0.2％

5064     5064  GAGCAAUUGUUGGCGAAAU    92.8％   5067     5067    UCCUUGAUCGGCUUCGCCG    92.7％

10080    5064  GAGCAAUUGUUGGUGAAAU    0.1％    10131    5067    UuCUUGAUCGGCUUCGCCG    1.5％

10081    5064  GAGCAgUUGUUGGCGAAAU    0.2％    10132    5067    UCaUUGAUCGGCUUCGCCG    0.1％

10082    5064  GAGuAAUUGUUGGCGAAAU    0.7％    10133    5067    UCCUUGAcCGGCUUCGCCG    3.1％

10083    5064  GgGCAAUUGUUGGCGAAAU    0.7％    10134    5067    UCCUUGAUaGGCUUCGCCG    0.1％

10084    5064  GgGCAAUUGUUGGCGAgAU    0.1％    10135    5067    UCCUUGAUCGaCUUCGCCG    0.8％

10085    5064  aAGCAAUUGUUGGCGAAAU    0.1％    10136    5067    UCCUUGAUCGGaUUCGCCG    0.1％

10086    5064  GAaCAAUUGUUGGCGAAAU    0.3％    10137    5067    UCCUUGAUCGGCUcCGCCG    0.7％

10087    5064  GAGCAAUUaUUGGCGAAAU    0.1％    10138    5067    UCCUUGAUCGGCUUCaCCG    0.1％

10088    5064  GAGCAAUUGUaGGCGAAAU    0.1％    10139    5067    UCCUUGAUCGGCUUCGCaG    0.1％

10089    5064  GAGCAAUUGUgGGCGAAAU    0.1％    10140    5067    UuCUcGAUCGGCUUCGCCG    0.1％

10090    5064  GAGCAAUUGUUGcCGAAAU    0.1％    10141    5067    UCCUUGAUaGaCUUCGCCG    0.1％

10142    5067    UCCUUGAcCGGgUUuGCCG    0.1％    10193    5070    CCUUGAUCGaCUUCGCaGA    0.1％

10143    5067    UuCUaGAcCGGCUUCGCCG    0.2％    10194    5070    CCUUGAcCGGgUUuGCCGA    0.1％

5068     5068    GGGAGCAAUUGUUGGCGAA    92.7％   5071     5071    GAGGGAGCAAUUGUUGGCG    92.3％

10144    5068    GGGAGCAAUUGUUGGuGAA    0.1％    10195    5071    GAGGGAGCAAUUGUUGGuG    0.1％

10145    5068    GGGAGCAgUUGUUGGCGAA    0.2％    10196    5071    GAGGGAGCAgUUGUUGGCG    0.2％

10146    5068    GGGAGuAAUUGUUGGCGAA    0.7％    10197    5071    GAGGGAGuAAUUGUUGGCG    0.7％

10147    5068    GGGgGCAAUUGUUGGCGAA    0.7％    10198    5071    GAGGGgGCAAUUGUUGGCG    0.8％

10148    5068    GGGgGCAAUUGUUGGCGAg    0.1％    10199    5071    aAGGGAGCAAUUGUUGGCG    0.2％

10149    5068    aGGAGCAAUUGUUGGCGAA    0.1％    10200    5071    GAaGGAGCAAUUGUUGGCG    0.1％

10150    5068    GGaAGCAAUUGUUGGCGAA    0.1％    10201    5071    GAGGaAGCAAUUGUUGGCG    0.1％

10151    5068    GGGAaCAAUUGUUGGCGAA    0.3％    10202    5071    GAGGGAaCAAUUGUUGGCG    0.3％

10152    5068    GGGAGCAAUUaUUGGCGAA    0.1％    10203    5071    GAGGGAGCAAUUaUUGGCG    0.1％

10153    5068    GGGAGCAAUUGUaGGCGAA    0.1％    10204    5071    GAGGGAGCAAUUGUaGGCG    0.1％

10154    5068    GGGAGCAAUUGUUGcCGAA    0.1％    10205    5071    GAGGGAGCAAUUGUUGcCG    0.1％

10155    5068    GGGcGCAAUUGUUGGCGAA    0.6％    10206    5071    GAGGGcGCAAUUGUUGGCG    0.6％

10156    5068    GGGAaCAAUUGUUGGuGAA    0.1％    10207    5071    GcGGGAGCAAUUGUUGGCG    0.2％

10157    5068    GGGgaCAAUUGUUGGCGAA    0.2％    10208    5071    GAGGGAaCAAUUGUUGGuG    0.1％

10158    5068    aGGAGCAAUUGUgGGCGAA    0.1％    10209    5071    GAGGGgaCAAUUGUUGGCG    0.2％

10159    5068    GGGAcgAAUUGUUGGCGAA    0.1％    10210    5071    GAaGGAGCAAUUGUgGGCG    0.1％

10160    5068    GGGAGCAAUcGUUGGaGAA    0.3％    10211    5071    GAGGAcgAAUUGUUGGCG     0.1％

10161    5068    aGGgGCAAUUGUaGGCGAA    0.1％    10212    5071    GAGGGAGCAAUcGUUGGaG    0.4％

10162    5068    GGGAGCAAUcGUUGGaGAg    0.1％    10213    5071    GAaGGgGCAAUUGUaGGCG    0.1％

5069     5069    AGGGAGCAAUUGUUGGCGA    92.5％   5072     5072    AGGGCUUUCACCGAAGAGG    92.3％

10163    5069    AGGGAGCAAUUGUUGGuGA    0.1％    10214    5072    AGGGCUUUCACCGAgGAGG    0.1％

10164    5069    AGGGAGCAgUUGUUGGCGA    0.2％    10215    5072    AGGGCUUUCACuGAAGAGG    0.3％

10165    5069    AGGGAGuAAUUGUUGGCGA    0.7％    10216    5072    AGGGCUUUCAuCGAAGAGG    0.1％

10166    5069    AGGGgGCAAUUGUUGGCGA    0.8％    10217    5072    AGGGCUUUuACCGAAGAGG    0.1％

10167    5069    AaGGAGCAAUUGUUGGCGA    0.1％    10218    5072    AGGGCUUUCACuGAgGAGG    0.1％

10168    5069    AGGaAGCAAUUGUUGGCGA    0.1％    10219    5072    AGaGCUUUCACCGAAGAGG    0.1％

10169    5069    AGGGAaCAAUUGUUGGCGA    0.3％    10220    5072    AGGGCcUUCACCGAAGAGG    0.7％

10170    5069    AGGGAGCAAUUaUUGGCGA    0.1％    10221    5072    AGGGCUaUCACCGAAGAGG    0.1％

10171    5069    AGGGAGCAAUUGUaGGCGA    0.1％    10222    5072    AGGGCUUUCACaGAAGAGG    0.1％

10172    5069    AGGGAGCAAUUGUUGcCGA    0.1％    10223    5072    AGGGCUUUCACCaAAGAGG    0.1％

10173    5069    AGGGcGCAAUUGUUGGCGA    0.6％    10224    5072    AGGGCUUUCACCGAAaAGG    0.2％

10174    5069    cGGGAGCAAUUGUUGGCGA    0.2％    10225    5072    AGGGCUUUCACCGAAGAaG    0.1％

10175    5069    AGGGAaCAAUUGUUGGuGA    0.1％    10226    5072    AGGGCUUUCACCGAAGcGG    0.2％

10176    5069    AGGGgaCAAUUGUUGGCGA    0.2％    10227    5072    AGGGgUUUCACCGAAGAGG    0.1％

10177    5069    AaGGAGCAAUUGUgGGCGA    0.1％    10228    5072    AGGGCcUUCACCGAgGAGG    2.0％

10178    5069    AGGGAcgAAUUGUUGGCGA    0.1％    5073     5073    GGGCUUUCACCGAAGAGGG    92.2％

10179    5069    AGGGAGCAAUcGUUGGaGA    0.4％    10229    5073    GGGCUUUCACCGAgGAGGG    0.1％

10180    5069    AaGGgGCAAUUGUaGGCGA    0.1％    10230    5073    GGGCUUUCACuGAAGAGGG    0.3％

5070     5070    CCUUGAUCGGCUUCGCCGA    92.4％   10231    5073    GGGCUUUCAuCGAAGAGGG    0.1％

10181    5070    CCUUGAUCGGCUUCGCCGg    0.3％    10232    5073    GGGCUUUuACCGAAGAGGG    0.1％

10182    5070    uCUUGAUCGGCUUCGCCGA    1.5％    10233    5073    GGGCUUUCACuGAgGAGGG    0.1％

10183    5070    CaUUGAUCGGCUUCGCCGA    0.1％    10234    5073    GaGCUUUCACCGAAGAGGG    0.1％

10184    5070    CCUUGAcCGGCUUCGCCGA    3.1％    10235    5073    GGGCcUUCACCGAAGAGGG    0.7％

10185    5070    CCUUGAUaGGCUUCGCCGA    0.1％    10236    5073    GGGCUaUCACCGAAGAGGG    0.1％

10186    5070    CCUUGAUCGaCUUCGCCGA    0.8％    10237    5073    GGGCUUUCACaGAAGAGGG    0.1％

10187    5070    CCUUGAUCGGaUUCGCCGA    0.1％    10238    5073    GGGCUUUCACCaAAGAGGG    0.1％

10188    5070    CCUUGAUCGGCUcCGCCGA    0.7％    10239    5073    GGGCUUUCACCGAAaAGGG    0.2％

10189    5070    CCUUGAUCGGCUUCaCCGA    0.1％    10240    5073    GGGCUUUCACCGAAGAaGG    0.1％

10190    5070    CCUUGAUCGGCUUCGCaGA    0.1％    10241    5073    GGGCUUUCACCGAAGAGGa    0.1％

10191    5070    uCUcGAUCGGCUUCGCCGA    0.1％    10242    5073    GGGCUUUCACCGAAGcGGG    0.2％

10192    5070    CCUUGAUaGaCUUCGCCGA    0.1％    10243    5073    GGGgUUUCACCGAAGAGGG    0.1％

10244  5073    GGGCcUUCACCGAgGAGGG    2.0％    10293  5078    AAGGGCUUUCACCGAgGAG    0.1％

5074   5074    AUAAGAUGGCUGAUUGAAG    92.1％   10294  5078    AAGGGCUUUCACuGAAGAG    0.3％

10245  5074    AUAAGAUGGCUGAUUGAgG    0.1％    10295  5078    AAGGGCUUUCAuCGAAGAG    0.1％

10246  5074    AUAAGAUGGuUGAUUGAAG    1.6％    10296  5078    AAGGGCUUUuACCGAAGAG    0.1％

10247  5074    AUAAGgUGGCUGAUUGAAG    1.8％    10297  5078    gAGGGCUUUCACCGAAGAG    0.4％

10248  5074    AUgAGAUGGCUGAUUGAAG    0.1％    10298  5078    AAGGGCUUUCACuGAgGAG    0.1％

10249  5074    AUAAGgUGGCUGAUUGAgG    0.1％    10299  5078    AAGaGCUUUCACCGAAGAG    0.1％

10250  5074    AUAAGAUGGCUaAUUGAAG    1.8％    10300  5078    AAGGGCcUUCACCGAAGAG    0.7％

10251  5074    AUAAGAUGGCUGAUcGAAG    0.3％    10301  5078    AAGGGCUaUCACCGAAGAG    0.1％

10252  5074    AUAAnAUGGCUGAUUGAAG    0.1％    10302  5078    AAGGGCUUUCACaGAAGAG    0.1％

10253  5074    AUAAGAUGGuUaAUUGAAG    2.0％    10303  5078    AAGGGCUUUCACCaAAGAG    0.1％

10254  5074    AUAAGgUGGuUaAUUGAAG    0.1％    10304  5078    AAGGGCUUUCACCGAAaAG    0.2％

5075   5075    UAAGAUGGCUGAUUGAAGA    92.1％   10305  5078    AAGGGCUUUCACCGAAGAa    0.1％

10255  5075    UAAGAUGGCUGAUUGAgGA    0.1％    10306  5078    AAGGGCUUUCACCGAAGcG    0.2％

10256  5075    UAAGAUGGuUGAUUGAAGA    1.6％    10307  5078    AAGGGgUUUCACCGAAGAG    0.1％

10257  5075    UAAGgUGGCUGAUUGAAGA    1.8％    10308  5078    uAGGGCUUUCACCGAAGAG    0.1％

10258  5075    UgAGAUGGCUGAUUGAAGA    0.1％    10309  5078    AAGGGCcUUCACCGAgGAG    2.0％

10259  5075    UAAGgUGGCUGAUUGAgGA    0.1％    5079   5079    UAAGGGCUUUCACCGAAGA    91.8％

10260  5075    UAAGAUGGCUaAUUGAAGA    1.8％    10310  5079    UAAGGGCUUUCACCGAgGA    0.1％

10261  5075    UAAGAUGGCUGAUcGAAGA    0.3％    10311  5079    UAAGGGCUUUCACuGAAGA    0.3％

10262  5075    UAAnAUGGCUGAUUGAAGA    0.1％    10312  5079    UAAGGGCUUUCAuCGAAGA    0.1％

10263  5075    UAAGAUGGuUaAUUGAAGA    2.0％    10313  5079    UAAGGGCUUUuACCGAAGA    0.1％

10264  5075    UAAGgUGGuUaAUUGAAGA    0.1％    10314  5079    UgAGGGCUUUCACCGAAGA    0.4％

5076   5076    AAGAUGGCUGAUUGAAGAA    91.9％   10315  5079    UAAGGGCUUUCACuGAgGA    0.1％

10265  5076    AAGAUGGCUGAUUGAAGAg    0.2％    10316  5079    aAAGGGCUUUCACCGAAGA    0.1％

10266  5076    AAGAUGGCUGAUUGAgGAA    0.1％    10317  5079    UAAGaGCUUUCACCGAAGA    0.1％

10267  5076    AAGAUGGuUGAUUGAAGAA    1.6％    10318  5079    UAAGGGCcUUCACCGAAGA    0.7％

10268  5076    AAGgUGGCUGAUUGAAGAA    1.8％    10319  5079    UAAGGGCUaUCACCGAAGA    0.1％

10269  5076    gAGAUGGCUGAUUGAAGAA    0.1％    10320  5079    UAAGGGCUUUCACaGAAGA    0.1％

10270  5076    AAGgUGGCUGAUUGAgGAA    0.1％    10321  5079    UAAGGGCUUUCACCaAAGA    0.1％

10271  5076    AAGAUGGCUaAUUGAAGAA    1.8％    10322  5079    UAAGGGCUUUCACCGAAaA    0.2％

10272  5076    AAGAUGGCUGAUcGAAGAA    0.3％    10323  5079    UAAGGGCUUUCACCGAAGc    0.2％

10273  5076    AAnAUGGCUGAUUGAAGAA    0.1％    10324  5079    UAAGGGgUUUCACCGAAGA    0.1％

10274  5076    AAGAUGGuUaAUUGAAGAA    2.0％    10325  5079    UuAGGGCUUUCACCGAAGA    0.1％

10275  5076    AAGgUGGuUaAUUGAAGAA    0.1％    10326  5079    UAAGGGCcUUCACCGAgGA    2.0％

5077   5077    CUAAGGGCUUUCACCGAAG    91.9％   5080   5080    GAUGGCUGAUUGAAGAAGU    91.7％

10276  5077    CUAAGGGCUUUCACCGAgG    0.1％    10327  5080    GAUGGCUGAUUGAAGAgGU    0.2％

10277  5077    CUAAGGGCUUUCACuGAAG    0.3％    10328  5080    GAUGGCUGAUUGAgGAAGU    0.1％

10278  5077    CUAAGGGCUUUCAuCGAAG    0.1％    10329  5080    GAUGGuUGAUUGAAGAAGU    1.6％

10279  5077    CUAAGGGCUUUuACCGAAG    0.1％    10330  5080    GgUGGCUGAUUGAAGAAGU    1.8％

10280  5077    CUgAGGGCUUUCACCGAAG    0.4％    10331  5080    GgUGGCUGAUUGAgGAAGU    0.1％

10281  5077    uUAAGGGCUUUCACCGAAG    0.1％    10332  5080    GAUGGCUaAUUGAAGAAGU    1.8％

10282  5077    CUAAGGGCUUUCACuGAgG    0.1％    10333  5080    GAUGGCUGAUcGAAGAAGU    0.3％

10283  5077    CaAAGGGCUUUCACCGAAG    0.1％    10334  5080    GAUGGCUGAUUGAAGAAaU    0.3％

10284  5077    CUAAGaGCUUUCACCGAAG    0.1％    10335  5080    nAUGGCUGAUUGAAGAAGU    0.1％

10285  5077    CUAAGGGCcUUCACCGAAG    0.7％    10336  5080    GAUGGuUaAUUGAAGAAGU    1.9％

10286  5077    CUAAGGGCUaUCACCGAAG    0.1％    10337  5080    GgUGGuUaAUUGAAGAAGU    0.1％

10287  5077    CUAAGGGCUUUCACaGAAG    0.1％    10338  5080    GAUGGuUaAUUGAAGAAaU    0.1％

10288  5077    CUAAGGGCUUUCACCaAAG    0.1％    5081   5081    AGAUGGCUGAUUGAAGAAG    91.7％

10289  5077    CUAAGGGCUUUCACCGAAa    0.2％    10339  5081    AGAUGGCUGAUUGAAGAgG    0.2％

10290  5077    CUAAGGGgUUUCACCGAAG    0.1％    10340  5081    AGAUGGCUGAUUGAgGAAG    0.1％

10291  5077    CUuAGGGCUUUCACCGAAG    0.1％    10341  5081    AGAUGGuUGAUUGAAGAAG    1.6％

10292  5077    CUAAGGGCcUUCACCGAgG    2.0％    10342  5081    AGgUGGCUGAUUGAAGAAG    1.8％

5078   5078    AAGGGCUUUCACCGAAGAG    91.8％   10343  5081    AGgUGGCUGAUUGAgGAAG    0.1％

10344  5081    AGAUGGCUaAUUGAAGAAG    1.8％    10394  5085    AAGCGAAUUUCAGUGUGgU    2.8％

10345  5081    AGAUGGCUGAUcGAAGAAG    0.3％    10395  5085    AgGCGAAUUUCAGUGUGAU    0.1％

10346  5081    AGAUGGCUGAUUGAAGAAa    0.3％    10396  5085    gAGCGAAUUUCAGUGUGAU    0.1％

10347  5081    AnAUGGCUGAUUGAAGAAG    0.1％    10397  5085    AAGCaAAUUUCAGUGUGAU    0.3％

10348  5081    AGAUGGuUaAUUGAAGAAG    1.9％    10398  5085    AAGCGAAcUUCAGUGUGAU    1.6％

10349  5081    AGgUGGuUaAUUGAAGAAG    0.1％    10399  5085    AAGCGAAUaUCAGUGUGAU    0.1％

10350  5081    AGAUGGuUaAUUGAAGAAa    0.1％    10400  5085    AAGCGAAUUUCAGcGUGAU    0.2％

5082   5082    ACUAAGGGCUUUCACCGAA    91.4％   10401  5085    AAGCGAAUUUCAGUGUaAU    0.2％

10351  5082    ACUAAGGGCUUUCACuGAA    0.3％    10402  5085    AAGCGAAUUUCAGUGUGAc    0.2％

10352  5082    ACUAAGGGCUUUCAuCGAA    0.1％    10403  5085    AAGCuAAUUUCAGUGUGAU    0.4％

10353  5082    ACUAAGGGCUUUuACCGAA    0.1％    10404  5085    AAGCaAAcUUCAGUGUGAU    0.9％

10354  5082    ACUgAGGGCUUUCACCGAA    0.4％    10405  5085    AAGCaAAcUUuAGUGUGAU    2.2％

10355  5082    AuUAAGGGCUUUCACCGAA    0.1％    5086   5086    GGCUUUCACCGAAGAGGGA    90.9％

10356  5082    gCUAAGGGCUUUCACCGAA    0.7％    10406  5086    GGCUUUCACCGAAGAGGGg    0.8％

10357  5082    ACUAAGGGCUUUCACuGAg    0.1％    10407  5086    GGCUUUCACCGAgGAGGGA    0.1％

10358  5082    gCUAAGGGCUUUCACCGAg    0.1％    10408  5086    GGCUUUCACuGAAGAGGGA    0.3％

10359  5082    ACaAAGGGCUUUCACCGAA    0.1％    10409  5086    GGCUUUCAuCGAAGAGGGA    0.1％

10360  5082    ACUAAGaGCUUUCACCGAA    0.1％    10410  5086    GGCUUUuACCGAAGAGGGA    0.1％

10361  5082    ACUAAGGGCcUUCACCGAA    0.7％    10411  5086    GGCUUUCACuGAgGAGGGA    0.1％

10362  5082    ACUAAGGGCUaUCACCGAA    0.1％    10412  5086    aGCUUUCACCGAAGAGGGA    0.1％

10363  5082    ACUAAGGGCUUUCACaGAA    0.1％    10413  5086    GGCcUUCACCGAAGAGGGA    0.5％

10364  5082    ACUAAGGGCUUUCACCaAA    0.1％    10414  5086    GGCUaUCACCGAAGAGGGA    0.1％

10365  5082    ACUAAGGGgUUUCACCGAA    0.1％    10415  5086    GGCUUUCACaGAAGAGGGA    0.1％

10366  5082    ACUuAGGGCUUUCACCGAA    0.1％    10416  5086    GGCUUUCACCaAAGAGGGA    0.1％

10367  5082    ACUAAGGGCcUUCACCGAg    2.0％    10417  5086    GGCUUUCACCGAAaAGGGA    0.2％

5083   5083    UACUAAGGGCUUUCACCGA    91.3％   10418  5086    GGCUUUCACCGAAGAaGGA    0.1％

10368  5083    UACUAAGGGCUUUCACuGA    0.4％    10419  5086    GGCUUUCACCGAAGAGGaA    0.1％

10369  5083    UACUAAGGGCUUUCAuCGA    0.1％    10420  5086    GGCUUUCACCGAAGAGGGc    0.6％

10370  5083    UACUAAGGGCUUUuACCGA    0.1％    10421  5086    GGCUUUCACCGAAGcGGGA    0.2％

10371  5083    UACUgAGGGCUUUCACCGA    0.4％    10422  5086    GGgUUUCACCGAAGAGGGA    0.1％

10372  5083    UAuUAAGGGCUUUCACCGA    0.1％    10423  5086    GGCcUUCACCGAAGAGGGg    0.2％

10373  5083    UgCUAAGGGCUUUCACCGA    0.8％    10424  5086    GGCcUUCACCGAgGAGGGA    2.0％

10374  5083    cACUAAGGGCUUUCACCGA    0.1％    5087   5087    GCUUUCACCGAAGAGGGAG    90.8％

10375  5083    UACaAAGGGCUUUCACCGA    0.1％    10425  5087    GCUUUCACCGAAGAGGGgG    0.8％

10376  5083    UACUAAGaGCUUUCACCGA    0.1％    10426  5087    GCUUUCACCGAgGAGGGAG    0.1％

10377  5083    UACUAAGGGCcUUCACCGA    2.7％    10427  5087    GCUUUCACuGAAGAGGGAG    0.3％

10378  5083    UACUAAGGGCUaUCACCGA    0.1％    10428  5087    GCUUUCAuCGAAGAGGGAG    0.1％

10379  5083    UACUAAGGGCUUUCACaGA    0.1％    10429  5087    GCUUUuACCGAAGAGGGAG    0.1％

10380  5083    UACUAAGGGCUUUCACCaA    0.1％    10430  5087    GCUUUCACuGAgGAGGGAG    0.1％

10381  5083    UACUAAGGGgUUUCACCGA    0.1％    10431  5087    GCcUUCACCGAAGAGGGAG    0.2％

10382  5083    UACUuAGGGCUUUCACCGA    0.1％    10432  5087    GCUaUCACCGAAGAGGGAG    0.1％

5084   5084    AAAGCGAAUUUCAGUGUGA    91.2％   10433  5087    GCUUUCACaGAAGAGGGAG    0.1％

10383  5084    AAAGCGAAUUUCAGUGUGg    2.8％    10434  5087    GCUUUCACCaAAGAGGGAG    0.1％

10384  5084    AAgGCGAAUUUCAGUGUGA    0.1％    10435  5087    GCUUUCACCGAAaAGGGAG    0.2％

10385  5084    AgAGCGAAUUUCAGUGUGA    0.1％    10436  5087    GCUUUCACCGAAGAaGGAG    0.1％

10386  5084    AAAGCaAAUUUCAGUGUGA    0.3％    10437  5087    GCUUUCACCGAAGAGGaAG    0.1％

10387  5084    AAAGCGAAcUUCAGUGUGA    1.6％    10438  5087    GCUUUCACCGAAGAGGGAa    0.1％

10388  5084    AAAGCGAAUaUCAGUGUGA    0.1％    10439  5087    GCUUUCACCGAAGAGGGAc    0.1％

10389  5084    AAAGCGAAUUUCAGcGUGA    0.2％    10440  5087    GCUUUCACCGAAGAGGGcG    0.6％

10390  5084    AAAGCGAAUUUCAGUGUaA    0.2％    10441  5087    GCUUUCACCGAAGcGGGAG    0.2％

10391  5084    AAAGCuAAUUUCAGUGUGA    0.4％    10442  5087    GgUUUCACCGAAGAGGGAG    0.1％

10392  5084    AAAGCaAAcUUCAGUGUGA    0.9％    10443  5087    GCcUUCACCGAgGAGGGAG    2.0％

10393  5084    AAAGCaAAcUUuAGUGUGA    2.2％    10444  5087    GCcUUCACCGAAGAGGGAa    0.3％

5085   5085    AAGCGAAUUUCAGUGUGAU    91.0％   10445  5087    GCUUUCACaGAAGAaGGAG    1.0％

10446  5087    GCcUUCACCGAAGAGGGga    0.2％    10497  5090  AAGAGGGgaCAAUUGUUGG    0.2％

10447  5087    GCUUUCACaGAAGAaGGgG    0.2％    10498  5090    AgGAGGGAGCAAUcGUUGG    0.1％

10448  5087    GCUUUCACgGAAGAaGGgG    0.1％    10499  5090    AAGAGGGAcgAAUUGUUGG    0.1％

5088   5088    AUUACUAAGGGCUUUCACC    90.8％   10500  5090    AAGAaGGgGCAAUUGUaGG    0.1％

10449  5088    AUUACUAAGGGCUUUCACu    0.3％    5091   5091    GAAGAGGGAGCAAUUGUUG    90.4％

10450  5088    AUUACUAAGGGCUUUCAuC    0.1％    10501  5091    GAAGAGGGAGCAgUUGUUG    0.2％

10451  5088    AUUACUAAGGGCUUUuACC    0.1％    10502  5091    GAAGAGGGAGuAAUUGUUG    0.7％

10452  5088    AUUACUgAGGGCUUUCACC    0.4％    10503  5091    GAAGAGGGgGCAAUUGUUG    0.8％

10453  5088    AUUAuUAAGGGCUUUCACC    0.1％    10504  5091    GAgGAGGGAGCAAUUGUUG    2.1％

10454  5088    AUUgCUAAGGGCUUUCACC    0.8％    10505  5091    aAAGAGGGAGCAAUUGUUG    0.1％

10455  5088    AcUACUAAGGGCUUUCACC    0.6％    10506  5091    GAAaAGGGAGCAAUUGUUG    0.2％

10456  5088    AUcACUAAGGGCUUUCACC    0.1％    10507  5091    GAAGAaGGAGCAAUUGUUG    0.1％

10457  5088    AUUACaAAGGGCUUUCACC    0.1％    10508  5091    GAAGAGGaAGCAAUUGUUG    0.1％

10458  5088    AUUACUAAGaGCUUUCACC    0.1％    10509  5091    GAAGAGGGAaCAAUUGUUG    0.4％

10459  5088    AUUACUAAGGGCcUUCACC    2.7％    10510  5091    GAAGAGGGAGCAAUcGUUG    0.3％

10460  5088    AUUACUAAGGGCUaUCACC    0.1％    10511  5091    GAAGAGGGAGCAAUUaUUG    0.1％

10461  5088    AUUACUAAGGGCUUUCACa    0.1％    10512  5091    GAAGAGGGAGCAAUUGUaG    0.1％

10462  5088    AUUACUAAGGGgUUUCACC    0.1％    10513  5091    GAAGAGGGcGCAAUUGUUG    0.6％

10463  5088    AUUACUuAGGGCUUUCACC    0.1％    10514  5091    GAAGcGGGAGCAAUUGUUG    0.2％

10464  5088    uUUACUAAGGGCUUUCACC    0.1％    10515  5091    GAAGAGGGgaCAAUUGUUG    0.2％

10465  5088    AcUACUAAGGGCUUUCACu    0.1％    10516  5091    GAgGAGGGAGCAAUcGUUG    0.1％

5089   5089    UUACUAAGGGCUUUCACCG    90.8％   10517  5091    GAAGAGGGAcgAAUUGUUG    0.1％

10466  5089    UUACUAAGGGCUUUCACuG    0.3％    10518  5091    GAAGAaGGgGCAAUUGUaG    0.1％

10467  5089    UUACUAAGGGCUUUCAuCG    0.1％    5092   5092    AGAGGGAGCAAUUGUUGGC    90.3％

10468  5089    UUACUAAGGGCUUUuACCG    0.1％    10519  5092    AGAGGGAGCAAUUGUUGGu    0.1％

10469  5089    UUACUgAGGGCUUUCACCG    0.4％    10520  5092    AGAGGGAGCAgUUGUUGGC    0.2％

10470  5089    UUAuUAAGGGCUUUCACCG    0.1％    10521  5092    AGAGGGAGuAAUUGUUGGC    0.7％

10471  5089    UUgCUAAGGGCUUUCACCG    0.8％    10522  5092    AGAGGGgGCAAUUGUUGGC    0.8％

10472  5089    CUACUAAGGGCUUUCACCG    0.6％    10523  5092    gGAGGGAGCAAUUGUUGGC    2.1％

10473  5089    UcACUAAGGGCUUUCACCG    0.1％    10524  5092    AaAGGGAGCAAUUGUUGGC    0.2％

10474  5089    UUACaAAGGGCUUUCACCG    0.1％    10525  5092    AGAaGGAGCAAUUGUUGGC    0.1％

10475  5089    UUACUAAGaGCUUUCACCG    0.1％    10526  5092    AGAGGaAGCAAUUGUUGGC    0.1％

10476  5089    UUACUAAGGGCcUUCACCG    2.7％    10527  5092    AGAGGGAaCAAUUGUUGGC    0.3％

10477  5089    UUACUAAGGGCUaUCACCG    0.1％    10528  5092    AGAGGGAGCAAUUaUUGGC    0.1％

10478  5089    UUACUAAGGGCUUUCACaG    0.1％    10529  5092    AGAGGGAGCAAUUGUaGGC    0.1％

10479  5089    UUACUAAGGGCUUUCACCa    0.1％    10530  5092    AGAGGGAGCAAUUGUUGcC    0.1％

10480  5089    UUACUAAGGGgUUUCACCG    0.1％    10531  5092    AGAGGGcGCAAUUGUUGGC    0.6％

10481  5089    UUACUuAGGGCUUUCACCG    0.1％    10532  5092    AGcGGGAGCAAUUGUUGGC    0.2％

10482  5089    cUACUAAGGGCUUUCACUG    0.1％    10533  5092    AGAGGGAaCAAUUGUUGGu    0.1％

5090   5090    AAGAGGGAGCAAUUGUUGG    90.4％   10534  5092    AGAGGGgaCAAUUGUUGGC    0.2％

10483  5090    AAGAGGGAGCAgUUGUUGG    0.2％    10535  5092    AGAGGGAcgAAUUGUUGGC    0.1％

10484  5090    AAGAGGGAGuAAUUGUUGG    0.7％    10536  5092    AGAGGGAGCAAUcGUUGGa    0.3％

10485  5090    AAGAGGGgGCAAUUGUUGG    0.8％    10537  5092    AGAaGGgGCAAUUGUaGGC    0.1％

10486  5090    AgGAGGGAGCAAUUGUUGG    2.1％    10538  5092    gGAGGGAGCAAUcGUUGGa    0.1％

10487  5090    AAaAGGGAGCAAUUGUUGG    0.2％    5093   5093    UCACCGAAGAGGGAGCAAU    90.3％

10488  5090    AAGAaGGAGCAAUUGUUGG    0.1％    10539  5093    UCACCGAAGAGGGAGCAgU    0.2％

10489  5090    AAGAGGaAGCAAUUGUUGG    0.1％    10540  5093    UCACCGAAGAGGGAGuAAU    0.7％

10490  5090    AAGAGGGAaCAAUUGUUGG    0.4％    10541  5093    UCACCGAAGAGGGgGCAAU    0.8％

10491  5090    AAGAGGGAGCAAUcGUUGG    0.3％    10542  5093    UCACCGAgGAGGGAGCAAU    2.1％

10492  5090    AAGAGGGAGCAAUUaUUGG    0.1％    10543  5093    UCACuGAAGAGGGAGCAAU    0.3％

10493  5090    AAGAGGGAGCAAUUGUaGG    0.1％    10544  5093    UCAuCGAAGAGGGAGCAAU    0.1％

10494  5090    AAGAGGGAGCAAUUGUUGc    0.1％    10545  5093    UuACCGAAGAGGGAGCAAU    0.1％

10495  5090    AAGAGGGcGCAAUUGUUGG    0.6％    10546  5093    UCACuGAgGAGGGAGCAAU    0.1％

10496  5090    AAGcGGGAGCAAUUGUUGG    0.2％    10547  5093    UCACaGAAGAGGGAGCAAU    0.1％

10548  5093    UCACCaAAGAGGGAGCAAU    0.1％    10600  5095    UUCACCGAAGcGGGAGCAA    0.2％

10549  5093    UCACCGAAaAGGGAGCAAU    0.2％    10601  5095    UUCACCGAAGAGGGgaCAA    0.2％

10550  5093    UCACCGAAGAaGGAGCAAU    0.1％    10602  5095    UUCACaGAAGAaGGAGCAA    1.0％

10551  5093    UCACCGAAGAGGaAGCAAU    0.1％    10603  5095    UUCACCGAAGAGGGAcgAA    0.1％

10552  5093    UCACCGAAGAGGGAaCAAU    0.4％    10604  5095    UUCACaGAAGAaGGgGCAA    0.2％

10553  5093    UCACCGAAGAGGGcGCAAU    0.6％    10605  5095    UUCACgGAAGAaGGgGCAA    0.1％

10554  5093    UCACCGAAGcGGGAGCAAU    0.2％    5096   5096    CUUUCACCGAAGAGGGAGC    90.1％

10555  5093    UCACCGAAGAGGGgaCAAU    0.2％    10606  5096    CUUUCACCGAAGAGGGAGu    0.7％

10556  5093    UCACaGAAGAaGGAGCAAU    1.0％    10607  5096    CUUUCACCGAAGAGGGgGC    0.8％

10557  5093    UCACCGAAGAGGGAcgAAU    0.1％    10608  5096    CUUUCACCGAgGAGGGAGC    0.1％

10558  5093    UCACaGAAGAaGGgGCAAU    0.2％    10609  5096    CUUUCACuGAAGAGGGAGC    0.3％

10559  5093    UCACgGAAGAaGGgGCAAU    0.1％    10610  5096    CUUUCAuCGAAGAGGGAGC    0.1％

5094   5094    UUUCACCGAAGAGGGAGCA    90.2％   10611  5096    CUUUuACCGAAGAGGGAGC    0.1％

10560  5094    UUUCACCGAAGAGGGAGuA    0.7％    10612  5096    CUUUCACuGAgGAGGGAGC    0.1％

10561  5094    UUUCACCGAAGAGGGgGCA    0.8％    10613  5096    CcUUCACCGAAGAGGGAGC    0.2％

10562  5094    UUUCACCGAgGAGGGAGCA    0.1％    10614  5096    CUaUCACCGAAGAGGGAGC    0.1％

10563  5094    UUUCACuGAAGAGGGAGCA    0.3％    10615  5096    CUUUCACaGAAGAGGGAGC    0.1％

10564  5094    UUUCAuCGAAGAGGGAGCA    0.1％    10616  5096    CUUUCACCaAAGAGGGAGC    0.1％

10565  5094    UUUuACCGAAGAGGGAGCA    0.1％    10617  5096    CUUUCACCGAAaAGGGAGC    0.2％

10566  5094    UUUCACuGAgGAGGGAGCA    0.1％    10618  5096    CUUUCACCGAAGAaGGAGC    0.1％

10567  5094    cUUCACCGAAGAGGGAGCA    0.2％    10619  5096    CUUUCACCGAAGAGGaAGC    0.1％

10568  5094    UaUCACCGAAGAGGGAGCA    0.1％    10620  5096    CUUUCACCGAAGAGGGAaC    0.1％

10569  5094    UUUCACaGAAGAGGGAGCA    0.1％    10621  5096    CUUUCACCGAAGAGGGcGC    0.6％

10570  5094    UUUCACCaAAGAGGGAGCA    0.1％    10622  5096    CUUUCACCGAAGcGGGAGC    0.2％

10571  5094    UUUCACCGAAaAGGGAGCA    0.2％    10623  5096    gUUUCACCGAAGAGGGAGC    0.1％

10572  5094    UUUCACCGAAGAaGGAGCA    0.1％    10624  5096    CcUUCACCGAgGAGGGAGC    2.0％

10573  5094    UUUCACCGAAGAGGaAGCA    0.1％    10625  5096    CcUUCACCGAAGAGGGAaC    0.3％

10574  5094    UUUCACCGAAGAGGGAaCA    0.1％    10626  5096    CUUUCACaGAAGAaGGAGC    1.0％

10575  5094    UUUCACCGAAGAGGGcGCA    0.6％    10627  5096    CUUUCACCGAAGAGGGAcg    0.1％

10576  5094    UUUCACCGAAGcGGGAGCA    0.2％    10628  5096    CcUUCACCGAAGAGGGgaC    0.2％

10577  5094    cUUCACCGAgGAGGGAGCA    2.0％    10629  5096    CUUUCACaGAAGAaGGgGC    0.2％

10578  5094    cUUCACCGAAGAGGGAaCA    0.3％    10630  5096    CUUUCACgGAAGAaGGgGC    0.1％

10579  5094    UUUCACaGAAGAaGGAGCA    1.0％    5097   5097    CCGAAGAGGGAGCAAUUGU    90.0％

10580  5094    UUUCACCGAAGAGGGAcgA    0.1％    10631  5097    CCGAAGAGGGAGCAgUUGU    0.2％

10581  5094    cUUCACCGAAGAGGGgaCA    0.2％    10632  5097    CCGAAGAGGGAGuAAUUGU    0.7％

10582  5094    UUUCACaGAAGAaGGgGCA    0.2％    10633  5097    CCGAAGAGGGgGCAAUUGU    0.8％

10583  5094    UUUCACgGAAGAaGGgGCA    0.1％    10634  5097    CCGAgGAGGGAGCAAUUGU    2.1％

5095   5095    UUCACCGAAGAGGGAGCAA    90.2％   10635  5097    CuGAAGAGGGAGCAAUUGU    0.3％

10584  5095    UUCACCGAAGAGGGAGCAg    0.2％    10636  5097    uCGAAGAGGGAGCAAUUGU    0.1％

10585  5095    UUCACCGAAGAGGGAGuAA    0.7％    10637  5097    CaGAAGAGGGAGCAAUUGU    0.1％

10586  5095    UUCACCGAAGAGGGgGCAA    0.8％    10638  5097    CCaAAGAGGGAGCAAUUGU    0.1％

10587  5095    UUCACCGAgGAGGGAGCAA    2.1％    10639  5097    CCGAAaAGGGAGCAAUUGU    0.2％

10588  5095    UUCACuGAAGAGGGAGCAA    0.3％    10640  5097    CCGAAGAaGGAGCAAUUGU    0.1％

10589  5095    UUCAuCGAAGAGGGAGCAA    0.1％    10641  5097    CCGAAGAGGaAGCAAUUGU    0.1％

10590  5095    UUuACCGAAGAGGGAGCAA    0.1％    10642  5097    CCGAAGAGGGAaCAAUUGU    0.4％

10591  5095    UUCACuGAgGAGGGAGCAA    0.1％    10643  5097    CCGAAGAGGGAGCAAUcGU    0.3％

10592  5095    aUCACCGAAGAGGGAGCAA    0.1％    10644  5097    CCGAAGAGGGAGCAAUUaU    0.1％

10593  5095    UUCACaGAAGAGGGAGCAA    0.1％    10645  5097    CCGAAGAGGGcGCAAUUGU    0.6％

10594  5095    UUCACCaAAGAGGGAGCAA    0.1％    10646  5097    CCGAAGcGGGAGCAAUUGU    0.2％

10595  5095    UUCACCGAAaAGGGAGCAA    0.2％    10647  5097    CCGAAGAGGGgaCAAUUGU    0.2％

10596  5095    UUCACCGAAGAaGGAGCAA    0.1％    10648  5097    CuGAgGAGGGAGCAAUcGU    0.1％

10597  5095    UUCACCGAAGAGGaAGCAA    0.1％    10649  5097    CCGAAGAGGGAcgAAUUGU    0.1％

10598  5095    UUCACCGAAGAGGGAaCAA    0.4％    10650  5097    CgGAAGAaGGgGCAAUUGU    0.1％

10599  5095    UUCACCGAAGAGGGcGCAA    0.6％    5098   5098    ACCGAAGAGGGAGCAAUUG    90.0％

10651  5098    ACCGAAGAGGGAGCAgUUG    0.2％    10681  5099    CGAAGAGGGAaCAAUUGUU    0.4％

10652  5098    ACCGAAGAGGGAGuAAUUG    0.7％    10682  5099    CGAAGAGGGAGCAAUcGUU    0.3％

10653  5098    ACCGAAGAGGGgGCAAUUG    0.8％    10683  5099    CGAAGAGGGAGCAAUUaUU    0.1％

10654  5098    ACCGAgGAGGGAGCAAUUG    2.1％    10684  5099    CGAAGAGGGAGCAAUUGUa    0.1％

10655  5098    ACuGAAGAGGGAGCAAUUG    0.3％    10685  5099    CGAAGAGGGcGCAAUUGUU    0.6％

10656  5098    AuCGAAGAGGGAGCAAUUG    0.1％    10686  5099    CGAAGcGGGAGCAAUUGUU    0.2％

10657  5098    ACaGAAGAGGGAGCAAUUG    0.1％    10687  5099    CGAAGAGGGgaCAAUUGUU    0.2％

10658  5098    ACCaAAGAGGGAGCAAUUG    0.1％    10688  5099    uGAgGAGGGAGCAAUcGUU    0.1％

10659  5098    ACCGAAaAGGGAGCAAUUG    0.2％    10689  5099    CGAAGAGGGAcgAAUUGUU    0.1％

10660  5098    ACCGAAGAaGGAGCAAUUG    0.1％    5100   5100    CACCGAAGAGGGAGCAAUU    90.0％

10661  5098    ACCGAAGAGGaAGCAAUUG    0.1％    10690  5100    CACCGAAGAGGGAGCAgUU    0.2％

10662  5098    ACCGAAGAGGGAaCAAUUG    0.4％    10691  5100    CACCGAAGAGGGAGuAAUU    0.7％

10663  5098    ACCGAAGAGGGAGCAAUcG    0.3％    10692  5100    CACCGAAGAGGGgGCAAUU    0.8％

10664  5098    ACCGAAGAGGGAGCAAUUa    0.1％    10693  5100    cACCGAgGAGGGAGCAAUU    2.1％

10665  5098    ACCGAAGAGGGcGCAAUUG    0.6％    10694  5100    CACuGAAGAGGGAGCAAUU    0.3％

10666  5098    ACCGAAGcGGGAGCAAUUG    0.2％    10695  5100    CAuCGAAGAGGGAGCAAUU    0.1％

10667  5098    ACCGAAGAGGGgaCAAUUG    0.2％    10696  5100    uACCGAAGAGGGAGCAAUU    0.1％

10668  5098    ACuGAgGAGGGAGCAAUcG    0.1％    10697  5100    CACaGAAGAGGGAGCAAUU    0.1％

10669  5098    ACCGAAGAGGGAcgAAUUG    0.1％    10698  5100    CACCaAAGAGGGAGCAAUU    0.1％

10670  5098    ACgGAAGAaGGgGCAAUUG    0.1％    10699  5100    CACCGAAaAGGGAGCAAUU    0.2％

5099   5099    CGAAGAGGGAGCAAUUGUU    90.0％   10700  5100    CACCGAAGAaGGAGCAAUU    0.1％

10671  5099    CGAAGAGGGAGCAgUUGUU    0.2％    10701  5100    CACCGAAGAGGaAGCAAUU    0.1％

10672  5099    CGAAGAGGGAGuAAUUGUU    0.7％    10702  5100    CACCGAAGAGGGAaCAAUU    0.4％

10673  5099    CGAAGAGGGgGCAAUUGUU    0.8％    10703  5100    CACCGAAGAGGGAGCAAUc    0.3％

10674  5099    CGAgGAGGGAGCAAUUGUU    2.1％    10704  5100    CACCGAAGAGGGcGCAAUU    0.6％

10675  5099    uGAAGAGGGAGCAAUUGUU    0.3％    10705  5100    CACCGAAGcGGGAGCAAUU    0.2％

10676  5099    aGAAGAGGGAGCAAUUGUU    0.1％    10706  5100    CACCGAAGAGGGgaCAAUU    0.2％

10677  5099    CaAAGAGGGAGCAAUUGUU    0.1％    10707  5100    CACuGAgGAGGGAGCAAUc    0.1％

10678  5099    CGAAaAGGGAGCAAUUGUU    0.2％    10708  5100    CACCGAAGAGGGAcgAAUU    0.1％

10679  5099    CGAAGAaGGAGCAAUUGUU    0.1％    10709  5100    CACgGAAGAaGGgGCAAUU    0.1％

10680  5099    CGAAGAGGaAGCAAUUGUU    0.1％

实施例16：siRNA静脉递送抑制体内流感病毒繁殖

本实施例证明靶向病毒NP转录子的siRNA预防性和感染后的静脉给药都显著抑制小鼠流感病毒复制(图2)。以下是示例性人类流感病毒保守靶序列(衍生自登记号AF389119)列表：

gccacugaaaucagagcau，(SEQ ID NO：10794)

ucagagcauccgucggaaa，(SEQ ID NO：10795)

ggacgauucuacauccaaa，(SEQ ID NO：10796)

cagcuuaacaauagagaga，(SEQ ID NO：10797)

gcuuaacaauagagagaau，(SEQ ID N0：10798)

aauagagagaauggugcuc，(SEQ ID NO：10799)

gggaaagauccuaagaaaa，(SEQ ID NO：10800)

ggaaagauccuaagaaaac，(SEQ ID NO：10801)

ugagagaacucauccuuua，(SEQ ID NO：10802)

uuaugacaaagaagaaaua，(SEQ ID NO：10803)

acaagaauugcuuaugaaa，(SEQ ID NO：10804)

gaauugcuuaugaaagaau，(SEQ ID NO：10805)

aagcaaugauggaucaagu，(SEQ ID N0：10806)

gcaaugauggaucaaguga，(SEQ ID NO：10807)

ugauggaucaagugagaga，(SEQ ID NO：10808)

ccacuagaggaguucaaau，(SEQ ID NO：10809)

cacuagaggaguucaaauu，(SEQ ID NO：10810)

gaggaaacaccaaucaaca，(SEQ ID NO：10811)

ggaaacaccaaucaacaga，(SEQ ID NO：10812)

gggccaaaucagcauacaa，(SEQ ID NO：10813)

caaccauuauggcagcauu，(SEQ ID NO：10814)

ccauuauggcagcauucaa，(SEQ ID NO：10815)

aggaugauggaaagugcaa，(SEQ ID NO：10816)

gaugauggaaagugcaaga，(SEQ ID NO：10817)

gaguaaugaaggaucuuau，(SEQ ID NO：10818)

ggaucuuauuucuucggag，(SEQ ID NO：10819)

gaucuuauuucuucggaga，(SEQ ID NO：10820)

ucuuauuucuucggagaca，(SEQ ID NO：10821)

ggaguacgacaauuaaaga，(SEQ ID NO：10822)

以下是对多种物种代表流感病毒NP基因序列的列表。加粗部分是这些序列共有的保守区。

流感毒株    流感NP基因保守区的核苷酸序列    SEQ ID NO

PR8(H1N1)，AATGAAGGATCTTATTTCTTCGGAGACAATGCAGAGGAGTACGACAATTA，  11471

WSN(H1N1)，AATGAAGGATCTTATTTCTTCGGGACAATGCAGAGGAGTACGACAATTA，   11472

Lenn.(H2N2)，AATGAAGGATCTTATTTCTTCGGAGACAATGCAGAGGAGTACGACAATTA，11473

HK(H2N2)，AATGAAGGATCTTATTTCTTCGGAGACAATGCAGAGGAGTACGACAATTA，   11474

Memphis(H3N2)，AATGAAGGATCTTATTTCTTCGGAGACAATGCAGAGGAGTACGACAATTA，11475

HK(H5N1)，AATGAAGGATCTTATTTCTTCGGAGACAATGCAGAGGAATATGACAATTG，  11476

Duck(H10N7)，AACGAGGGATCTTATTTCTTCGGAGACAATGCAGAGGAATATGACAATTA，  11477

Equine(H7N7)，AATGAAGGGTCTTATTTCTTCGGAGACAATGCTGAGGAGTTTGACAGTTA，  11478

Whale (H13N2)，AATGAGGGATCTTATTTCTTCGGAGACAATGCTGAGGAGTATGACAATTG，  11479

Chicken(H9N2)，AATGAAGGATCTTATTTCTTCGGAGACAATGCATAGGAGTATGACAATTA，  11480

Swine(H4N6)，AACGAAGGGTCTTATTTCTTCGGAGACAATGCAGAGGAATATGACAATTA，  11481

为了检测病毒靶向siRNA的预防用途，NP-1496(INFsi-9)与阳离子递送聚合物jetPEI(Qbiogene)混合并静脉注射(IV)(2mg/Kg)于C57BL/6小鼠。三小时后，以1×10⁴PR8病毒颗粒接种(鼻内)小鼠以起始感染，24小时后处死小鼠以使用MDCK血凝素检测来检测肺匀浆的病毒滴度。

如图2所示，未接受siRNA处理(NT；填充方块)或接受靶向于GFP的siRNA(GFP 60μg；空白方块)的小鼠的肺匀浆的平均log₁₀TCID₅₀是4.2。以30μg靶向于NP的siRNA(NP 30μg；空白圆圈)和jetPEI预处理的小鼠中肺匀浆的平均log₁₀TCID₅₀是3.9。以60μg靶向于NP的siRNA(NP 60μg；填充圆圈)和jetPEI预处理的小鼠中肺匀浆的平均log₁₀TCID₅₀是3.2。无处理组和接受60μgNP siRNA组的肺匀浆病毒滴度之间的差异是显著的(P＝0.0002)。

为了评价siRNA对已有流感感染作为治疗处理，以PR8病毒鼻内感染小鼠，五小时后，静脉给药NP-1496/ietPEI或PA-2087/jetPEI混合物。感染28小时后使用MDCK-HA检测来检测肺的病毒滴度。相对于未处理的感染小鼠，所有处理都显著减少病毒滴度；以NP-1496处理的小鼠中观察到剂量-响应性病毒滴度减少(图3)。小鼠中还观察到感染后24小时siRNA处理的抑制效应。

进一步，设计的siRNA还可保护小鼠不受禽流感病毒的致死攻击。注射对照(GFP-靶向)siRNA并随后以致死剂量H1N1(PR8)、H5N1或H7N7病毒攻击的小鼠(2×)，持续减重并在7-10日死于感染，如图4所示。然而，接受组合siRNANP-1496和PA-2087的感染小鼠从最初的体重减轻中恢复。至少50％小鼠在H7N7致死攻击中存活，87％小鼠在H5N1致死攻击中存活，100％小鼠在H1N1致死攻击中存活。因此，对流感病毒基因组保守区特异性的siRNA赋予了宽的保护，包括针对高致病性禽流感病毒的保护(图4)。

实施例17a：siRNA的鼻内递送抑制小鼠流感产生

本实施例证明靶向于病毒NP转录子的siRNA预防性鼻内给药抑制流感病毒复制并以剂量依赖性方式减少小鼠病毒RNA水平。

流感通常在上呼吸道和肺中感染和复制。因此，由于可到达性，局部给药对流感预防和治疗是理想的，即鼻内和/或肺递送药物。尤其是，鼻内和/或肺递送siRNA对治疗流感病毒感染是有利的，因为：1)当使用局部递送途经时易于达到高的局部siRNA浓度，因此比系统递送需要较少siRNA；2)鼻内和/或肺递送方法是非侵袭性的。因此，在流感小鼠模型中进行了鼻内siRNA递送。

不同于导致可忽略沉默效应的常规静脉递送裸siRNA，鼻内递送siRNA(未修饰的，PBS或盐水中)可在肺中检测，并能沉默内源基因表达或抑制肺组织中病毒繁殖。为了检测靶向流感的siRNA的非侵袭性递送酌效力，鼻内递送NP-1496 siRNA(PBS中)。以所指量的PBS中的NP特异性siRNA或PBS对照鼻内处理BALB/c小鼠。2小时后，所有小鼠鼻内感染PR8血清型(1000pfu)。感染24小时后收集肺，由MDCK-HA检测从肺匀浆测量病毒滴度。PBS组和0.5、1、2mg/kg siRNA处理组之间的P值表示统计显著性。数据显示于图5。

没有载体的情况下，裸NP靶向siRNA有效抑制小鼠肺中病毒繁殖(图5；感染24小时后)。抑制是剂量依赖性的，感染2小时前递送2mg/kg siRNA时观察到7倍减少。

还在较高浓度研究了鼻内递送NP靶向siRNA(10mg/kg，感染3小时前递送)的效力，使用靶mRNA表达(定量RT-PCR)和病毒滴度(MDCK-HA)来测量效力。BALB/c小鼠鼻内给药对照和NP靶向siRNA(10mg/kg，PBS中)。3小时后，所有小鼠鼻内感染PR8病毒(50pfu/小鼠)。感染24小时和48小时后收集肺，从左肺提取总RNA。使用dT18引物将总mRNA反转录为cDNA。使用PB1特异性引物进行实时PCR，以定量病毒mRNA水平。GAPDH用作内对照。将右肺和中肺匀浆，由MDCK-HA检测测量病毒滴度。感染48小时后样品中病毒滴度示于图6，使用student t检测发现PBS组和NP siRNA处理组之间的统计显著性(p＝0.01)；感染24小时后样品中的病毒滴度太低而检测不到，可能是由于siRNA引导的抑制。

结果显示于图6。图6比较了标准化的定量PCR结果和病毒滴度检测结果。感染24小时后测量的病毒mRNA水平显示55.2％抑制，但感染48小时后仅观察到很小的抑制。相反，小鼠肺样品的MDCK-HA检测表示在第2天84.6％病毒滴度抑制。相对于测量活病毒颗粒的MDCK-HA检测，病毒mRNA定量可能在反映病毒复制早期变化方面更敏感。因此，在第2天病毒mRNA抑制的减少可能是因为那时小鼠肺中RNAi效应减少。

还比较了鼻内递送的靶向NP转录子的裸siRNA与流感治疗Tamiflu对流感病毒滴度的效应。相对于GFP对照siRNA观察到的病毒滴度水平，鼻内递送的裸siRNA与Tamiflu治疗都减少流感病毒滴度。

还指出了鼻内递送siRNA G1498(INFsi-8)后NP-病毒转录子靶向对病毒滴度的效应。G1498 siRNA表现出体外减少病毒滴度的强效力，因此被选择在体内进一步鉴定。该研究的对照是未修饰的靶向荧光素酶的siRNA(Dharmacon；Luc)。该研究中使用体重范围为18-22克的10周大的雌性BALB/c(Taconic)。每个研究组有10只小鼠。小鼠以2mg/kg、5mg/kg、10mg/kg、20mg/kg和30mg/kg给药PBS中的G1498 siRNA。对照组给药同样的，除了都不给药2mg/kg剂量。siRNA给药4小时后以30μl PBS中的30 pfu PR8流感病毒感染。感染48小时后，收集小鼠肺，在MDCK细胞中以TCID₅₀检测测量其病毒滴度。

结果示于图7。TCID₅₀检测的结果表示2 mg/kg的G1498 siRNA抑制小鼠流感生产86％，5mg/kg和10 mg/kg的抑制90.6％，20mg/kg的抑制96.6％，30mg/kg的抑制95.2％。与单独PBS或Luc对照siRNA研究组相比，鼻内给药G1498 siRNA的小鼠总体上显示显著差异(P＜0.001)。总体上，接受PBS的小鼠与接受Luc siRNA的小鼠组相比没有表现显著差异(P＞0.05)。接受一种剂量G1498 siRNA的每个研究组显著不同于30mg/kg的PBS组或Luc siRNA对照研究组(P＜0.05)。最后，接受G1498siRNA剂量范围的小鼠未观察到显著的剂量响应。

实施例17b：siRNA的鼻内递送抑制非流感小鼠模型中亲环蛋白B表达

本实施例证明经由鼻内给药的裸siRNA的气道细胞摄取不是流感感染细胞的特有现象。此外，鼻内递送的裸siRNA还减少健康小鼠肺中内源基因亲环蛋白B的表达。以10mg/kg亲环蛋白B特异性siRNA(Dharmacon)或PBS中的GFP siRNA或PBS对照鼻内处理Balb/c小鼠。每组有5只小鼠。24小时后收集小鼠肺。从肺样品纯化总RNA，使用dT18引物进行反转录。使用亲环蛋白B特异性引物(Applied Biosystem)进行实时PCR，以定量靶mRNA水平。GAPDH-特异性引物(Applied Biosystem)在PCR中用作对照。

如图8所示，小鼠接受鼻内递送10mg/kg亲环蛋白B siRNA24小时后肺中亲环蛋白B mRNA被抑制70％。这些数据表示经由鼻内给药的裸siRNA的气道细胞摄取不是流感感染细胞的特有现象。鼻内递送裸siRNA也能达到健康动物中健康细胞的内源基因沉默。该发现对siRNA的预防用途是高度相关的，其可在无感染的情况下发生。

实施例18：鼻内给药蜗状siRNA制品后减少小鼠流感病毒滴度

本实施例证明以蜗状递送制品(BDSI，North Carolina)鼻内给药G1498siRNA比裸siRNA增强小鼠中流感病毒抑制。对本实施例，测试的制品示于表21。

表21.鼻内给药于小鼠的制品

研究组	制品
		缓冲液(对照)	TES+2mM Ca+2
蜗状安慰剂	40mg DOPS/ml
		蜗状亲环蛋白B siRNA	起始物质的4mg/ml(10mg/kg)siRNA(HPLC的0.963mg/ml)
蜗状未脂化G1498 siRNA(U-flu)	起始物质的4mg/ml siRNA(HPLC的2.752mg/ml)
		蜗状脂化G1 498 siRNA(L-flu)	起始物质的4mg/ml siRNA(HPLC的1.546mg/ml)
裸未脂化G1498 siRNA(U-flu)	起始物质的6.8mg/ml siRNA(HPLC的2.752mg/ml)
		裸未脂化G1498 siRNA(U-flu)	起始物质的10mg/ml siRNA(4mg/mlHPLC)
裸脂化G1498 siRNA(U-flu)	起始物质的10mg/ml siRNA(4mg/mlHPLC)

上述制品在流感感染5小时后鼻内给药。感染48小时后测量全肺的病毒滴度。除了裸未脂化U-flu组有5只小鼠以外，每个研究组有10只小鼠。

肺病毒滴度结果示于图9。图上的每个点代表一只动物。以One-Way-Anova进行统计。带有星号的数字表示平均值与对照(安慰剂或缓冲液)相比有统计差异。图8的数据表示相对于裸G1498 siRNA和对照(仅缓冲液或蜗状安慰剂)，鼻内递送的带有蜗状递送制品的G1498 siRNA显示出更大的病毒滴度减少。接受蜗状制品或裸脂化siRNA的所有组都观察到一定程度的毒性。

实施例19：静脉给药蜗状siRNA制品后减少小鼠流感病毒滴度

本实施例证明以蜗状递送制品静脉给药G1498 siRNA比裸siRNA增强小鼠中流感病毒抑制。测试的制品示于表22。

表22.静脉给药于小鼠的制品

研究组	制品
		缓冲液(对照)	TES+2mM Ca+2
蜗状安慰剂	40mg DOPS/ml
		蜗状亲环蛋白B siRNA	起始物质的1mg/ml(10mg/kg)siRNA(HPLC的0.607mg/ml)
蜗状未脂化G1498 siRNA(U-flu)	起始物质的1mg/ml siRNA(HPLC的1.196mg/ml)
		蜗状脂化G1498 siRNA(L-flu)	起始物质的1mg/ml siRNA(0.381mg/mlHPLC)
裸未脂化G1498 siRNA(U-flu)	起始台物质的10mg/ml siRNA(4mg/mlHPLC)

上述制品在流感感染5小时后静脉给药。感染48小时后测量全肺的病毒滴度。除了裸未脂化U-flu组有5只小鼠以外，每个研究组有10只小鼠。

肺病毒滴度结果示于图10A。图上的每个点代表一只动物。以One-Way-Anova进行统计。带有星号的数字表示平均值与对照(安慰剂或缓冲液)相比有统计差异。图9的数据表示相对于对照(仅缓冲液或蜗状安慰剂)，静脉给药的带有蜗状递送制品的G1498 siRNA显示出更大的病毒滴度减少。而且，静脉给药的U-flu制品还减少肺病毒滴度。

以蜗状制品递送的静脉给药siRNA还产生剂量响应图谱。测试的制品示于表23。

表23.静脉给药于小鼠用于研究剂量响应的制品

研究组	制品
		缓冲液(对照)	TES+2mM Ca+2
蜗状亲环蛋白B siRNA	起始物质的2.5mg/ml(10mg/kg)siRNA
		蜗状未脂化G1498 siRNA(U-flu)	起始物质的2.5mg/ml siRNA
蜗状未脂化G1498 siRNA(L-flu)	起始物质的1mg/ml siRNA
		蜗状未脂化G1498 siRNA(U-flu)	起始物质的0.4mg/ml siRNA
蜗状未脂化G1498 siRNA(U-flu)	起始物质的0.15mg/ml siRNA

上述制品在流感感染5小时后静脉给药。感染48小时后测量全肺的病毒滴度。除了裸未脂化U-flu组有5只小鼠以外，每个研究组有10只小鼠。

肺病毒滴度结果示于图10B。图上的每个点代表一只动物。以One-Way-Anova进行统计。带有星号的数字表示平均值与对照(安慰剂或缓冲液)相比有统计差异。图10的数据表示相对于缓冲液对照，静脉给药的带有蜗状递送制品的G1498 siRNA显示出更大的病毒滴度减少。而且，还观察到剂量响应。随着G1498 siRNA在蜗状制品中剂量增加，观察到小鼠肺病毒滴度的更大减少。

遵照为了测量小鼠病毒滴度的同样实验方案和步骤，列于表23的制品通过口饲给药于小鼠。肺病毒滴度结果示于图10B。如此前所述，每个点代表一只小鼠。所测试制品之间没有观察到统计差异。此外，研究组都没有观察到毒性。

实施例20：流感感染前后若丹明-蜗状物在小鼠肺中的分布

本实施例证明若丹明-蜗状物无siRNA制品的鼻内给药比静脉或口饲给药显示了若丹明的广泛分布。对本发明，若丹明包裹在无siRNA的蜗状物中。流感感染前4小时或感染后4小时，若丹明-蜗状物制品经由鼻内(40mg/ml，50μl/小鼠)、静脉(10mg/ml，200μl/小鼠)或口饲(10mg/ml，200μl/小鼠)给药。最后注射或感染5小时后收集小鼠肺组织，以干冰冷冻，切片用于分析。冷冻切片以DAPI对核染色并成像。

流感感染前和感染后的结果对所有组是相似的。然而，经受鼻内给药若丹明-蜗状物制品的组在肺切片中显示若丹明的宽分布。经受静脉给药的组在肺切片中显示一些若丹明的聚集，但具有有限的分布阳性信号。口饲的个体不显示阳性信号。这些数据表示以鼻内给药能最好地达到用于治疗呼吸道病毒感染的肺中蜗状物制品的彻底分布。肺中的彻底分布对有效减少病毒滴度很重要。

实施例21.产生和测试衍生自副流感病毒的siRNA

使用上述方法或从公众可获得的序列鉴别副流感病毒核蛋白。使用上述方法从编码副流感病毒核蛋白的核酸中鉴别siRNA。

表24-A列出了作为siRNA副流感病毒核蛋白靶序列的19-核苷酸区。所提供的19核苷酸区作为设计多种siRNA分子的有义链是有用的，该分子任选地在有义链和反义链中的任一条或两条都具有不同的3’突出端。因此，本领域技术人员将明白，从表24A-B所列每条序列可获得大量有义和反义siRNA。

此处提供的表24A-B和所有其它公开了衍生自病毒(除了上述对流感病毒)的靶序列的表格还公开了称为“保守靶序列”的靶序列的子集。这些保守靶序列在大量病毒核蛋白序列中是高度保守的。

此处提供的表24A-B和所有其它公开了衍生自具有非分段基因组的负链病毒的靶序列的表格还公开了5’核苷酸在病毒核蛋白基因中的位置。

表24A.人类副流感病毒-2(登记号NC003443)
						5’核苷酸位置	靶序列	SEQIDNO	5’核苷酸位置	保守靶序列	SEQ IDNO
81	ccgguaacgauuccaguuu	10823	81	ccgguaacgauuccaguuu	10823
						83	gguaacgauuccaguuuua	10824	83	gguaacgauuccaguuuua	10824
263	ggguauuugucaucaauaa	10825	263	ggguauuugucaucaauaa	10825
						264	gguauuugucaucaauaau	10826	264	gguauuugucaucaauaau	10826
294	cguaagaucuagacuuuua	10827	294	cauaagaucuagacuuuua	10827
						375	ccucagucuuuuaucacua	10828	375	ccucagucuuuuaucacua	10828
408	gaguaaucacaucaaauua	10829	408	gaguaaucacaucaaauua	10829
						439	ccagaagccagcaugaua	10830	439	ccagaagccagcauagaua	10830
449	gcauagauagaguagagau	10831	449	gcauagauagaguagagau	10831
						450	cauagauagaguagagaua	10832	450	cauagauagaguagagaua	10832
465	gauaacaggguuugagaau	10833	465	gauaacaggguuugagaau	10833
						473	gguuugagaauaauucauu	10834	473	gguuugagaauaauucauu	10834
502	ccagaugcucgaucaacua	10835	502	ccagaugcucgaucaacua	10835
						527	gaggagaggugcuggcuuu	10836	527	gaggagaggugcuggcuuu	10836
556	gcugaggacauuccugaua	10837	556	gcugaggacauuccugaua	10837
						561	ggacauuccugauacccuu	10838	561	ggacauuccugauacccuu	10838
585	ccaaacuccauuuguaaau	10839	585	ccaaacuccauugguaaau	10839
						666	gcuuaugcaggcauggaua	10840	666	gcuuaugcaggcauggaua	10840
741	ggcuaaauaucaacaacaa	10841	741	ggcuaaauaucaacaacaa	10841
						761	ggagaaucaaugcuaggua	10842	761	ggagaaucaaugcuaggua	10842
762	gagaaucaaugcuagguau	10843	762	gagaaucaaugcuagguau	10843
						790	ccugaagcacaaagacuaa	10844	790	ccugaagcacaaagacuaa	10844
796	gcacaaagacuaauucaga	10835	796	gcacaaagacuaauucaga	10845
						822	ccgcaagucaaugguagua	10846	822	ccgcaagucaaugguagua	10846
892	gcaaaccgcuacuaugcua	10847	955	ggauuuuucuuaacacuua	10849
						942	cagcggaaugggaggauuu	10848	1025	gggaacuccagaaauuaaa	10852
955	ggauuuuucuuaacacuua	10849	1082	ccaaguacauggcucuauu	10853
						985	ggaacaagauggccuacau	10850	1086	guacauggcucuauuagaa	10854
1024	ggggaacuccagaaauuaa	10851	1106	caccaaaacugauggauuu	10855
						1025	gggaacuccagaaauuaaa	10852	1133	cugaauauccauuagauua	10856
1082	ccaaguacauggcucuauu	10853	1164	ggguauuggaacuguccuu	10857
						1086	guacauggcucuauuagaa	10854	1172	gaacuguccuugauacaaa	10858
1106	caccaaaacugauggauuu	10855	1183	gauacaaauaugagaaauu	10859
						1133	cugaauauccauuagauua	10856	1204	gcauacgguagaucauauu	10860
1164	ggguauuggaacuguccuu	10857	1209	cgguagaucauauuuaaau	10861
						1172	gaacuguccuugauacaaa	10858	1217	cauauuuaaaucagcaaua	10862
1183	gauacaaauaugagaaauu	10859	1247	gaguagaaacagcaaggaa	10863
						1204	gcauacgguagaucauauu	10860	1307	gcaugacugcugcagacaa	10864
1209	cgguagaucauauuuaaau	10861	1308	caugacugcugcagacaaa	10865

1217	cauauuuaaaucagcaaua	10862	1339	gcaaccauaucaaagcuau	10866
						1247	gaguagaaacagcaaggaa	10863	1398	cccauuugcuggagcaaau	10867
1307	gcaugacugcugcagacaa	10864	1408	ggagcaaaugacagagaaa	10868
						1308	caugacugcugcagacaaa	10865	1419	cagagaaaugggaggacaa	10869
1339	gcaaccauaucaaagcuau	10866	1428	gggaggacaagcaaaugau	10870
						1398	cccauuugcuggagcaaau	10867	1429	ggaggacaagcaaaugaua	10871
1408	ggagcaaaugacagagaaa	10868	1453	guguauaacuucaauccaa	10872
						1419	cagagaaaugggaggacaa	10869	1512	ggacagaauugacaacgau	10873
1428	gggaggacaagcaaaugau	10870	1515	cagaauugacaacgaucaa	10874
						1429	ggaggacaagcaaaugaua	10871	1589	gugacaaccagcagagauu	10875
1453	guguauaacuucaauccaa	10872	1621	ccgcaaagaacaucaggua	10876
						1512	ggacagaauugacaacgau	10873	1622	cgcaaagaacaucagguau	10877
1515	cagaauugacaacgaucaa	10874	1682	gugcuaugcaugagcaaua	10878
						1589	gugacaaccagcagagauu	10875	1710	ccaggaugaugaugccaau	10879
1621	ccgcaaagaacaucaggua	10876	1713	ggaugaugaugccaaugau	10880
						1622	cgcaaagaacaucagguau	10877	1733	ccacagaugggaaugacau	10881
1682	gugcuaugcaugagcaaua	10878
						1710	ccaggaugaugaugccaau	10879
1713	ggaugaugaugccaaugau	10880
						1733	ccacagaugggaaugacau	10881
1781	ccuaacucucaaugucaua	10882
						1887	cggaaacaauucucucaua	10883
1888	ggaaacaauucucccauaa	10884

体外分析

以不同浓度的siRNA转染肺上皮细胞系A549细胞。Dharmacon的Sicontrol用作对照siRNA。Lipofectamine 2000用作转染剂，并根据制造商的说明。4小时后，以人类副流感病毒(hPIV)感染转染的A549细胞。在合适的时间点收集细胞，分离RNA。如Hino等(5)所述的进行RT和实时PCR。收集siRNA转染细胞和PIV感染细胞的培养上清液。将上清液的2-倍稀释物与0.05％豚鼠红细胞(6)混合，进行血凝素检测而测量病毒滴度。A549细胞也首先感染hPIV，在合适时间点转染不同浓度的siRNA。在合适时间点收集细胞和上清液。从细胞分离RNA，如上所述以基因特异性引物进行RT和实时PCR以确定siRNA的沉默效力。使用如上所述的血凝素检测和实时PCR中的病毒非靶基因特异性引物(如聚合酶)来测量病毒复制的减少。

体内分析

麻醉的Balb/c小鼠鼻内给药2-10mg/kg剂量的修饰或未修饰siRNA，带有或不带有制品。Dharmacon的Sicontrol以同样剂量给药。合适的时间点后以10⁷人类副流感3型感染动物。病毒感染后不同时间点杀死动物，收集肺组织。对病毒核衣壳基因进行实时PCR以确定病毒复制(5)。还使用肺匀浆来通过上述血凝素检测(6)确定病毒滴度。为了研究siRNA的治疗价值，首先以hPIV-3感染动物然后在最佳时间点给药hPIV特异性siRNA和对照siRNA。由上述方法监控肺组织中的病毒感染。

实施例22.产生和测试衍生自hMPV病毒的siRNA

使用上述方法或从公众可获得的序列鉴别人类MPV病毒核蛋白。使用上述方法从编码MPV核蛋白的核酸中鉴别siRNA。

表25列出了作为siRNA人类偏肺病毒核蛋白靶序列的19-核苷酸区。图1A证明人类偏肺病毒核蛋白序列与其衍生的共有序列之间的比对。所提供的19核苷酸区作为设计多种siRNA分子的有义链是有用的，该分子任选地在有义链和反义链中的任一条或两条都具有不同的3’突出端。因此，本领域技术人员将明白，从表25所列每条序列可获得大量有义和反义siRNA。

表25.人类偏肺病毒(登记号AY297748)
						5’核苷酸位置	靶序列	SEQ IDNO		保守靶序列	SEQ IDNO
60	cuucaagggauucaccuaa	10885	60	cuucaagggauucaccuaa	10885
						74	ccuaagugaucugucauau	10886	74	ccuaagugaucugucauau	10886
75	cuaagugaucugucauaua	10887	75	cuaagugaucugucauaua	10887
						86	gucauauaaacaugcuaua	10888	86	gucauauaaacaugcuaua	10888
88	cauauaaacaugcuauauu	10889	88	cauauaaacaugcuauauu	10889
						111	gagucucaauacacaauaa	10890	111	gagucucaauacacaauaa	10890
122	cacaauaaaaagagaugua	10891	122	cacaauaaaaagagaugua	10891
						166	caucauugcagcaagagau	10892	174	cagcaagagauaacacuuu	10894

173	gcagcaagagauaacacuu	10893	198	ggagagauucuuuacacua	10895
						174	cagcaagagauaacacuuu	10894	199	gagagauucuuuacacuaa	10896
198	ggagagauucuuuacacua	10895	214	cuaaacauacugauuacaa	10897
						199	gagagauucuuuacacuaa	10896	230	caaauaugcugcagagaua	10898
214	cuaaacauacugauuacaa	10897	240	gcagagauagggauacaau	10899
						230	caaauaugcugcagagaua	10898	241	cagagauagggauacaaua	10900
240	gcagagauagggauacaau	10899	243	gagauagggauacaauaua	10901
						241	cagagauagggauacaaua	10900	245	gauagggauacaauauauu	10902
243	gagauagggauacaauaua	10901	249	gggauacaauauauuugca	10903
						245	gauagggauacaauauauu	10902	269	ggcucuaggaucagaaaga	10904
249	gggauacaauauauuugca	10903	280	cagaaagaguacaacagau	10905
						269	ggcucuaggaucagaaaga	10904	282	gaaagaguacaacagauuu	10906
280	cagaaagaguacaacagau	10905	288	guacaacagauuuuaagaa	10907
						282	gaaagaguacaacagauuu	10906	313	gcagugaaguucagguggu	10909
288	guacaacagauuuuaagaa	10907	381	gaguugcaaauguuagaua	10919
						291	caacagauuuuaagaaauu	10908	383	guugcaaauguagauaua	10920
313	gcagugaaguucagguggu	10909	386	gcaaauguuagauauacau	10921
						314	cagugaaguucaggugguu	10910	396	gauauacauggaguggaaa	10922
341	gacauacucuuuagggaaa	10911	416	gaguuggguagaagaaaua	10924
						347	cucuuuagggaaagguaaa	10912	421	ggguagaagaaauagacaa	10925
354	gggaaagguaaaaauagua	10913	422	gguagaagaaauagacaaa	10926
						355	ggaaagguaaaaauaguaa	10914	429	gaaauagacaaagaggcaa	10927
356	gaaagguaaaaauaguaaa	10915	435	gacaaagaggcaagaaaaa	10928
						375	ggggaagaguugcaaaugu	10916	444	gcaagaaaaacaaugguga	10929
376	gggaagaguugcaaauguu	10917	454	caauggugacuuugcuaaa	10931
						377	ggaagaguugcaaauguua	10918	467	gcuaaaggaaucaucaggu	10933
381	gaguugcaaauguuagaua	10919	468	cuaaaggaaucaucaggua	10934
						383	guugcaaauguuagauaua	10920	481	cagguaacaucccacaaaa	10935
386	gcaaauguuagauauacau	10921	506	gccuucagcaccagacaca	10938
						396	gauauacauggaguggaaa	10922	513	gcaccagacacaccaauaa	10939
410	ggaaaagaguuggguagaa	10923	514	caccagacacaccaauaau	10940
						416	gaguuggguagaagaaaua	10924	516	ccagacacaccaauaauuu	10941
421	ggguagaagaaauagacaa	10925	541	guguaggugcuuuaauauu	10942
						422	gguagaagaaauagacaaa	10926	547	gugcuuuaauauucacuaa	10943
429	gaaauagacaaagaggcaa	10927	562	cuaaacuagcaucaacaau	10944
						435	gacaaagaggcaagaaaaa	10928	588	ggacuagagacuacaguua	10945
444	gcaagaaaaacaaugguga	10929	663	ccgaagauugcuagaucuu	10951
						448	gaaaaacaauggugacuuu	10930	676	gaucuuucuaugaacuauu	10952
454	caauggugacuuugcuaaa	10931	705	guguauuacaggagucuau	10953
						459	gugacuuugcuaaaggaau	10932	715	ggagucuauucauugagua	10954
467	gcuaaaggaaucaucaggu	10933	716	gagucuauucauugaguau	10955
						468	cuaaaggaucaaucaggua	10934	735	gggaaagcuuuaggcucau	10956
481	c agguaacauccacaaaa	10935	741	gcuuuaggcucaucuucaa	10957
						492	ccacaaaaccagaggccuu	10936	747	ggcucaucuucaacaggaa	10958
500	ccagaggccuucagcacca	10937	763	gaagcaaagcagaaaguuu	10959
						506	gccuucagcaccagacaca	10938	774	gaaaguuuguuuguaaaua	10963
513	gcaccagacacaccaauaa	10939	778	guuuguuuguaaauauauu	10964
						514	caccagacacaccaauaau	10940	816	ggucaaacaaugcuaaggu	10966

516	ccagacacaccaauaauuu	10941	836	gggugucauugccagauca	10967
						541	guguaggugcuuuaauauu	10942	846	gccagaucaucuaacaaca	10968
547	gugcuuuaauauucacuaa	10943	847	ccagaucaucuaacaacau	10969
						562	cuaaacuagcaucaacaau	10944	850	gaucaucuaacaacauaau	10971
588	ggacuagagacuacaguua	10945	860	caacauaaugcuaggacau	10972
						623	gcuaagugaugcgcucaaa	10946	883	cugugcaagcugaauugaa	10973
628	gugaugcgcucaaaagaua	10947	891	gcugaauugaagcaaguua	10974
						638	caaaagauacccuagggua	10948	953	gcuuuuacaucuaagacaa	10979
652	ggguagauauaccgaagau	10949	1038	gcuucaggucuagguauaa	10980
						657	gauauaccgaagauugcua	10950	1091	gcuauuuucugcagcagaa	10982
663	ccgaagauugcuagaucuu	10951	1104	gcagaaaguuaugccagaa	10983
						676	gaucuuucuaugaacuauu	10952	1116	gccagaagcuuaaaagaaa	10984
705	guguauuacaggagucuau	10953	1123	gcuuaaaagaaagcaacaa	10985
						715	ggagucuauucauugagua	10954	1163	gcucacagacgaagaaaaa	10986
716	gagucuuuucauugaguau	10955
						735	gggaaagcuuuaggcucau	10956
741	gcuuuaggcucaucuucaa	10957
						747	ggcucaucuucaacaggaa	10958
763	gaagcaaagcagaaaguuu	10959
						767	caaagcagaaaguuuguuu	10960
771	gcagaaaguuuguuuguaa	10961
						772	cagaaaguuuguuuguaaa	10962
774	gaaaguuuguuuguaaaua	10963
						778	guuuguuuguaaauauauu	10964
804	gcuuauggagccggucaaa	10965
						816	ggucaaacaaugcuaaggu	10966
836	gggugucauugccagauca	10967
						846	gccagaucaucuaacaaca	10968
847	ccagaucaucuaacaacau	10969
						848	cagaucaucuaacaacaua	10970
850	gaucaucuaacaacauaau	10971
						860	caacauaaugcuaggacau	10972
883	cugugcaagcugaauugaa	10973
						891	gcugaauugaagcaaguua	10974
899	gaagcaaguuacagagguu	10975
						906	guuacagaggguuuaugauu	10976
914	gguuuaugauuuggugaga	10977
						939	gguccugaaucugggcuuu	10978
953	gcuuuuacaucuaagacaa	10979
						1038	gcuucaggucuagguauaa	10980
1044	ggucuagguauaaucggaa	10981
						1091	gcuauuuucugcagcagaa	10982
1104	gcagaaaguuaugccagaa	10983
						1116	gccagaagcuuaaaagaaa	10984
1123	gcuuaaaagaaagcaacaa	10985
						1163	gcucacagacgaagaaaaa	10986

体外分析

不同浓度siRNA电穿孔之后或之前合适的时间点，以预先确定的感染复数(MOI)的hMPV感染猴肾上皮细胞系LLC-MK2细胞。Dharmacon的Sicontrol用作对照siRNA。在合适的时间点收集细胞，分离总RNA。Oligo dT用作引物由反转录合成cDNA的第一条链。如Boivin等(1)所述的方法以病毒靶基因特异性引物进行实时PCR以确定siRNA的沉默效力。还使用实时PCR中的病毒非靶基因特异性引物(如聚合酶)来测量病毒复制的减少。如Tripp等(2)所述方法以病毒噬菌斑检测来确定病毒滴度。

体内分析

麻醉的Balb/c小鼠鼻内给药2-10mg/kg剂量的修饰或未修饰siRNA，带有或不带有制品。Dharmacon的Sicontrol以同样剂量给药。合适的时间点后以10⁶人类偏肺病毒感染动物。病毒感染后不同时间点杀死动物，收集肺组织。如体外检测中所述的，对N基因进行实时PCR以确定病毒复制(1)。还使用肺匀浆来通过LLC-MK2细胞的噬菌斑检测(16)确定病毒滴度。为了研究siRNA的治疗价值，首先以hMPV感染动物然后在最佳时间点给药hMPV特异性siRNA和对照siRNA。由上述方法监控肺组织中的病毒感染。

实施例23.产生和测试衍生自RSV病毒的siRNA

使用上述方法或从公众可获得的序列鉴别RSV病毒核蛋白。使用上述方法从编码RSV病毒核蛋白的核酸中鉴别siRNA。

表26列出了作为siRNA人类呼吸道合胞病毒核蛋白靶序列的19-核苷酸区。所提供的19核苷酸区作为设计多种siRNA分子的有义链是有用的，该分子任选地在有义链和反义链中的任一条或两条都具有不同的3’突出端。因此，本领域技术人员将明白，从表26所列每条序列可获得大量有义和反义siRNA。

表26.人类呼吸道合胞病毒(登记号NC 001781)
						5’核苷酸位置	靶序列	SEQIDNO		保守靶序列	SEQIDNO
1246	ccaauuaugaugugcaaaa	10987	1246	ccaauuaugaugugcaaaa	10987
						1259	gcaaaaacaccuaaacaaa	10988	1289	gcuauuaaucacugaagau	10989
1289	gcuauuaaucacugaagau	10989	1326	ggauuaauagguauguuau	10991
						1313	ucauaaauucacaggauua	10990	1347	gcuauguccagguuaggaa	10992
1326	ggauuaauagguauguuau	10991	1362	ggaagggaagacacuauaa	10993
						1347	gcuauguccagguuaggaa	10992	1385	acuuaaagaugcuggauau	10996
1362	ggaagggaagacacuauaa	10993	1398	ggauaucauguuaaagcua	10997
						1366	gggaagacacuauaaagau	10994	1419	ggaguagauauaacaacau	11000
1367	ggaagacacuauaaagaua	10995	1440	cgucaagauauaaauggaa	11001
						1385	acuuaaagaugcuggauau	10996	1460	ggaaaugaaauucgaagua	11004
1398	ggauaucauguuaaagcua	10997	1540	ccuacaaaaaaaugcuaaa	11005
						1406	uguuaaagcuaauggagua	10998	1566	ggagaaguggcuccagaau	11008
1413	gcuaauggaguagauauaa	10999	1578	ccagaauauaggcaugauu	11009
						1419	ggaguagauauaacaacau	11000	1599	ccagacugugggaugauaa	11010
1440	cgucaagauauaaauggaa	11001	1632	gcacuuguaauaaccaaau	11012
						1445	agauauaaauggaaaggaa	11002	1659	ggagacagaucaggucuua	11013
1446	gauauaaauggaaaggaaa	11003	1695	gcaaacaaugucuuaaaaa	11016
						1460	ggaaaugaaauucgaagua	11004	1811	gcacuuuggcauugcacaa	11019
1540	ccuacaaaaaaaugcuaaa	11005	1845	gguaguagaguugaaggaa	11020
						1553	gcuaaaagagaugggagaa	11006	1929	gccaaaucguaaaaaaaua	11023
1565	gggagaaguggcuccagaa	11007	1930	ccaaaucuguaaaaaauau	11024
						1566	ggagaaguggcuccagaau	11008	1962	gcuaguguccaggcagaaa	11025
1578	ccagaauauaggcaugauu	11009	2121	gcagcaggucuaggcauaa	11028
						1599	ccagacugugggaugauaa	11010	2132	aggcauaaugggagaguau	11029
1609	ggaugauaauacuguguau	11011	2199	gcagagcaacucaagaaaa	11031
						1632	gcacuuguaauaaccaaau	11012	2223	guaauaaacuacaguguau	11033
1659	ggagacagaucaggucuua	11013	2288	cccuaaagaagaugaugua	11035
						1680	gcaguaauuaggagggcaa	11014
1693	gggcaaacaaugucuuaaa	11015
						1695	gcaaacaaugucuuaaaaa	11016
1734	ggucucauaccaaaggaua	11017
						1748	ggauauagcuaacaguuuu	11018
1811	gcacuuuggcauugcacaa	11019
						1845	gguaguagaguugaaggaa	11020
1899	gggcaaguaaugcuaagau	11021
						1910	gcuaagauggggaguuuua	11022
1929	gccaaaucuguaaaaaaua	11023
						1930	ccaaaucuguaaaaaauau	11024
1962	gcuaguguccaggcagaaa	11025
						1985	gcaaguuguggaagucuau	11026
2064	gcaucauugcugucauuaa	11027
						2121	gcagcaggucuaggcauaa	11028
2132	aggcauaaugggagaguau	11029

2160	ccaagaaaccaggaucuuu	11030
						2199	gcagagcaacucaaagaaa	11031
2210	caaagaaaauggaguaaua	11032
						2223	guaauaaacuacaguguau	11033
2269	ccauaaagaaucaacucaa	11034
						2288	cccuaaagaagaugaugua	11035
2309	gcuuaaguuaacaaaaaa	11036

体外分析

以不同浓度的siRNA转染肺上皮细胞系A549细胞(3)。Dharmacon的Sicontrol用作对照siRNA。Lipofectamine 2000用作转染剂，并根据制造商的说明。4小时后，以hRSV感染转染的A549细胞。在合适的时间点收集细胞，分离RNA。如上所述的进行RT和实时PCR。将siRNA转染细胞和RSV感染细胞的培养上清液成倍稀释，稀释物用于感染A549细胞以在病毒噬菌斑检测(4)中确定病毒滴度。A549细胞也首先感染RSV，在合适时间点转染不同浓度的siRNA。在合适时间点收集细胞，分离RNA。如上所述以基因特异性引物进行RT和实时PCR以确定siRNA的沉默效力。使用实时PCR中的病毒非靶基因特异性引物(如聚合酶)来测量病毒复制的减少。

体内分析

异氟醚麻醉的Balb/c小鼠鼻内给药2mg/kg的PBS中的NP特异性、RSV特异性siRNA，每只小鼠50ul。Dharmacon的PBS中的Sicontrol以同样剂量给药。感染4小时后收集小鼠肺并匀浆。肺匀浆的10倍系列稀释物用于感染A549细胞。感染3至5天后监控细胞病变效应(4)。50％的细胞显示细胞病变效应的稀释物确定为TCID50。为了研究siRNA的治疗价值，首先以RSV感染动物然后在最佳时间点给药RSV特异性siRNA和对照siRNA。由上述方法监控肺组织中的病毒感染。

实施例24.产生和测试衍生自冠状病毒的siRNA

使用上述方法或从公众可获得的序列鉴别冠状病毒核蛋白。使用上述方法从编码冠状病毒核蛋白的核酸中鉴别siRNA。

表27列出了作为siRNA人类冠状病毒核蛋白靶序列的19-核苷酸区。所提供的19核苷酸区作为设计多种siRNA分子的有义链是有用的，该分子任选地在有义链和反义链中的任一条或两条都具有不同的3’突出端。因此，本领域技术人员将明白，从表27所列每条序列可获得大量有义和反义siRNA。

表27.人类冠状病毒(登记号AY391777)
						5’核苷酸位置	靶序列	SEQ IDNO	5’核苷酸位置	保守靶序列	SEQIDNO
29119	gguaagcaauccaguagua	11037	29119	gguaagcaauccaguagua	11037
						29259	gcaaccaucaggagggaau	11038	29259	gcaaccaucaggagggaau	11038
29305	ggaauuacucaguuucaaa	11039	29305	ggaauuacucaguuucaaa	11039
						29325	gggaaaggaguuugaguuu	11040	29325	gggaaaggaguuugaguuu	11040
29642	cgguacucccucaggguua	11041	29642	cgguacucccucaggguua	11041
						29686	gcuccuaauuccagaucua	11042	29686	gcuccuaauuccagaucua	11042
29879	ccaaagaagucagacagaa	11043	29879	ccaaagaagucagacagaa	11043
						29880	caaagaagucagacagaaa	11044	29880	caaagaagucagacagaaa	11044

以不同浓度的siRNA转染肺上皮细胞系A549细胞。Dharmacon的Sicontrol用作对照siRNA。Lipofectamine 2000用作转染剂，并根据制造商的说明。4小时后，以冠状病毒感染转染的A549细胞。在合适的时间点收集细胞，分离RNA。如上所述的进行RT和实时PCR(8)。收集siRNA转染细胞和RSV感染细胞的培养上清液。将上清液的2-倍稀释物与0.05％鸡红细胞(9)混合，进行血凝素检测。A549细胞也首先感染人类冠状病毒，在合适时间点转染不同浓度的siRNA。在最优时间点收集细胞和上清液。从细胞分离RNA，如上所述以基因特异性引物进行RT和实时PCR以确定siRNA的沉默效力。使用如上所述的血凝素检测和实时PCR中的病毒非靶基因特异性引物(如聚合酶)来测量病毒复制的减少。

实施例25.产生和测试衍生自西尼罗病毒的siRNA

使用上述方法或从公众可获得的序列鉴别西尼罗病毒核蛋白。使用上述方法从编码西尼罗病毒核蛋白的核酸中鉴别siRNA。

表28列出了作为siRNA人类西尼罗病毒核蛋白靶序列的19-核苷酸区。所提供的19核苷酸区作为设计多种siRNA分子的有义链是有用的，该分子任选地在有义链和反义链中的任一条或两条都具有不同的3’突出端。因此，本领域技术人员将明白，从表28所列每条序列可获得大量有义和反义siRNA。

表28.西尼罗病毒(登记号AY842931)
						5’核苷酸位置	靶序列	SEQ  IDNO	5’核苷酸位置	保守靶序列	SEQ  IDNO
98	cuauguugagccugaucga	11045	98	cuauguugagccugaucga	11045
						158	ucuucagguucacagcaau	11046	158	ucuucagguucacagcaau	11046
162	cagguucacagcaauugcu	11047	162	cagguucacagcaauugcu	11047
						192	agugcuggaucgauggaga	11048	199	gaucgauggagagguguga	11049
199	gaucgauggagagguguga	11049	203	gauggagaggugugaacaa	11050
						203	gauggagaggugugaacaa	11050	206	ggagaggugugaacaaaca	11051
206	ggagaggugugaacaaaca	11051	219	caaacaaacagcgaugaaa	11052
						219	caaacaaacagcgaugaaa	11052	220	aaacaaacagcgaugaaac	11053
220	aaacaaacagcgaugaaac	11053	221	aacaaacagcgaugaaaca	11054
						221	aacaaacagcgaugaaaca	11054	223	caaacagcgaugaaacacc	11055
223	caaacagcgaugaaacacc	11055	224	aaacagcgaugaaacaccu	11056
						224	aaacagcgaugaaacaccu	11056	227	cagcgaugaaacaccuucu	11057
227	cagcgaugaaacaccuucu	11057	229	gcgaugaaacaccuucuga	11058
						229	gcgaugaaacaccuucuga	11058	230	cgaugaaacaccuucugag	11059
230	cgaugaaacaccuucugag	11059	231	gaugaaacaccuucugagu	11060
						231	gaugaaacaccuucugagu	11060	238	caccuucugaguuuuaaga	11061
238	caccuucugaguuuuaaga	11061	256	aaggaacuagggaccuuga	11063
						252	uaagaaggaacuagggacc	11062	259	gaacuagggaccuugacca	11064
256	aaggaacuagggaccuuga	11063	265	gggaccuugaccagugcua	11065
						259	gaacuagggaccuugacca	11064	266	ggaccuugaccagugcuau	11066
265	gggaccuugaccagugcua	11065	270	cuugaccagugcuaucaau	11067
						266	ggaccuugaccagugcuau	11066	289	cggcggagcucaaaacaaa	11068
270	cuugaccagugcuaucaau	11067	292	cggagcucaaaacaaaaga	11069
						289	cggcggagcucaaaacaaa	11068	293	ggagcucaaaacaaaagaa	11070
292	cggagcucaaaacaaaaga	11069	294	gagcucaaaacaaaagaaa	11071
						293	ggagcucaaaacaaaagaa	11070
294	gagcucaaaacaaaagaaa	11071

体外分析

对病毒母液生产，以ATCC或CDC获得的西尼罗病毒(WNV)在0.1-1的感染复数感染Vero细胞，并培养在补充2％FBS的培养基中。感染后72-96小时收集培养上清液并澄清，此时50-70％的细胞表现细胞病变效应(CPE)。母液中感染性病毒的浓度通过在96孔板中Vero细胞上滴定而确定，并计算为ID₅₀/ml。1ID₅₀等于1感染单位(i.u.)。

为了发现最有效的siRNA序列，首先以不同浓度许多siRNA转染/电穿孔Vero细胞或任何其它合适细胞系，如幼仓鼠肾(BHK)细胞系(BHK-21)。Dharmacon的Sicontrol用作对照siRNA。在转染/电穿孔后合适的时间点，以优化moi的西尼罗病毒感染细胞。感染后不同时间点收集细胞并收集上清液。为了评价siRNA对病毒感染/复制的效力，从细胞分离RNA，并反转录生成cDNA的第一条链。以N基因特异性引物对WNVN基因进行实时PCR(10)，扩增产物与对照比较以评价siRNA的效力。使用出版的实验步骤(11)在病毒滴度检测中测试培养上清液。Vero或BHK-21细胞也首先感染WNV，在合适时间点转染不同浓度的siRNA。在合适时间点收集细胞，分离RNA。如上所述以基因特异性引物进行RT和实时PCR以确定siRNA的沉默效力。使用实时PCR中的病毒非靶基因特异性引物(如聚合酶)来测量病毒复制的减少。还使用上述方法检测病毒滴度。

体内分析

BALB/c小鼠已经显示为有效支持WNV复制。我们计划使用此株系来评价siRNA在细胞培养检测中的效力。具体地，对小鼠静脉给药2-10mg/kg剂量的修饰或未修饰siRNA，带有或不带有制品。Dharmacon的Sicontrol以同样剂量给药。合适的时间点后以WNV感染动物。在合适时间点从这些动物收集脑组织和血，对Vero或BHK-21细胞(11)噬菌斑滴定来确定血和脑中的病毒滴度。除了这个预防方法，我们还计划做治疗模型，其中首先以病毒感染动物，然后给予siRNA治疗。以如上所述的方法监控血和脑组织中的病毒感染。

实施例26.产生和测试衍生自登革热病毒的siRNA

使用上述方法或从公众可获得的序列鉴别登革热病毒核蛋白。使用上述方法从编码登革热病毒核蛋白的核酸中鉴别siRNA。

表29列出了作为siRNA登革热病毒核蛋白靶序列的19-核苷酸区。所提供的19核苷酸区作为设计多种siRNA分子的有义链是有用的，该分子任选地在有义链和反义链中的任一条或两条都具有不同的3’突出端。因此，本领域技术人员将明白，从表29所列每条序列可获得大量有义和反义siRNA。

表29.登革热病毒(登记号NC 001474)
						5’核苷酸位置	靶序列	SEQ ID NO	5’核苷酸位置	保守靶序列	SEQ  IDNO
96	gaugaaugaccaacggaaa	11072	96	gaugaaugaccaacggaaa	11072
						109	cggaaaaaggcgagaaaca	11073	109	cggaaaaaggcgagaaaca	11073
119	cgagaaacacgccuuucaa	11074	119	cgagaaacacgccuuucaa	11074
						150	cgagagaaaccgcguguca	11075	170	cuguacaacaguugacaaa	11077
159	ccgcgugucaacuguacaa	11076	210	gcagggacgaggaccacua	11078
						170	cuguacaacaguugacaaa	11077	213	gggacgaggaccacuaaaa	11079
210	gcagggacgaggaccacua	11078	273	cccaccaacagcagggaua	11080
						213	gggacgaggaccacuaaaa	11079	274	ccaccaacagcagggauau	11081
273	cccaccaacagcagggaua	11080	277	ccaacagcagggauauuaa	11082
						274	ccaccaacagcagggauau	11081	303	gggaacaauuaaaaaauca	11083
277	ccaacagcagggauauuaa	11082	304	ggaacaauuaaaaaaucaa	1108
						303	gggaacaauuaaaaaauca	11083	350	ggaaagagauuggaaggau	11085
304	ggaacaauuaaaaaaucaa	11084	404	gcaugaucaucaugcugau	11086
						350	ggaaagagauuggaaggau	11085
404	gcaugaucaucaugcugau	11086

体外分析

在C6/36蚊子细胞系中繁殖(DEN1-4)。为了测试siRNA沉默基因的效力，以不同浓度的许多siRNA转染/电穿孔Vero细胞。Dharmacon的Sicontrol用作对照siRNA。在转染/电穿孔后合适的时间点，以优化moi的登革热病毒(DEN1-4)感染细胞。感染后不同时间点收集细胞并收集上清液。为了评价siRNA对病毒感染/复制的效力，从细胞分离RNA，并反转录生成cDNA的第一条链。以基因特异性引物对登革热核衣壳/衣壳基因进行实时PCR，扩增产物与非siRNA转染感染的对照比较以评价siRNA的效力(1)。实时PCR中还使用病毒非靶基因特异性引物(如preM)来测量病毒复制的减少。使用Vero或BHK-21细胞(12)在病毒滴度检测中测试培养上清液以确定病毒滴度。还以上述方法测试了DEN感染Vero细胞后这些siRNA在病毒感染/复制中的效力。

体内分析

对体内评价siRNA，使用显示为对登革热2型(DEN2)感染更易感的A/J小鼠。对小鼠静脉给药2-10mg/kg剂量的修饰或未修饰siRNA，带有或不带有制品。Dharmacon的Sicontrol以同样剂量给药。合适的时间点后以DEN-2病毒静脉感染动物(1×10⁸p.f.u./小鼠)。以来自血提取的RNA的登革病毒特异性引物进行实时PCR分析来检测siRNA对登革热-2的效力(16)。还使用Vero细胞(12)对这些样品进行病毒噬菌斑检测。除了这个预防方法，我们还计划做治疗模型，其中首先以病毒感染动物，然后给予siRNA治疗。以如上所述的方法监控脑组织中的病毒感染。

实施例27.产生和测试衍生自鼻病毒的siRNA

使用上述方法或从公众可获得的序列鉴别鼻病毒核蛋白。使用上述方法从编码鼻病毒核蛋白的核酸中鉴别siRNA。

表30列出了作为siRNA鼻病毒-16核蛋白靶序列的19-核苷酸区。所提供的19核苷酸区作为设计多种siRNA分子的有义链是有用的，该分子任选地在有义链和反义链中的任一条或两条都具有不同的3’突出端。因此，本领域技术人员将明白，从表30所列每条序列可获得大量有义和反义siRNA。

表30.鼻病毒-16(登记号L24917(衣壳))
						5’核苷酸位置	靶序列	SEQ  IDNO	5’核苷酸位置	保守靶序列	SEQ IDNO
630	gcgcucaaguaucuagaca	11087	630	gcgcucaaguaucuagaca	11087
						632	gcucaaguaucuagacaga	11088	632	gcucaaguaucuagacaga	11088
656	gguacgcacucaacacaaa	11089	656	gguacgcacucaacacaaa	11089
						669	cacaaaauaugguaucaaa	11090	689	ggauccagccucaauuauu	11091
689	ggauccagccucaauuauu	11091	697	ccucaauuauuuuaacauu	11092
						697	ccucaauuauuuuaacauu	11092	840	guguagaagcuuguggaua	11095
808	ggagaaaggcauacccacu	11093	848	gcuuguggauacucugaua	11096
						829	gcaaucucagugguagaa	11094	852	guggauacucugauagaau	11097
840	guguagaagcuuguggaua	11095	854	ggauacucugauagaauaa	11098
						848	gcuuguggauacucugaua	11096	861	cugauagaauaauccaaau	11099
852	guggauacucugauagaau	11097	863	gauagaauaauccaaauua	11100
						854	ggauacucugauagaauaa	11098	898	cauaacaucucaagauguu	11101
861	cugauagaauaaauccaaau	11099	903	caucucaagauguugcuaa	11102
						863	gauaggaauaauccaaauua	11100	964	gcaggaugcaacggcuaua	11105
898	cauaacaucucaagauguu	11101	998	ccagauacaucaucaaaua	11106
						903	caucucaagauguugcuaa	11102	1079	ccagaugcucuuaaagaca	11107
918	cuaaugcagugguugggua	11103	1085	gcucuuaaagacaugggua	11108
						962	ccgcaggaugcaacggcua	11104	1086	cucuuaaagacauggguau	11109
964	gcaggaugcaacggcuaua	11105	1088	cuuaaagacauggguauuu	11110
						998	ccagauacaucaucaaaua	11106	1099	ggguauuuuuggugaaaau	11111
1079	ccagaugcucuuaaagaca	11107	1152	cagugcacguacagugcaa	11113
						1085	gcucuuaaagacaugggua	11108	1214	ccagaacaccaguuuagcua	11117
1086	cucuuaaagacauggguau	11109	1321	gaaacaaccuagugaugau	11125
						1088	cuuaaagacauggguauuu	11110	1334	gaugauaauuggcuaaauu	11126
1099	ggguauuuuuggugaaaau	11111	1345	gcuaaauuuugaugguaca	11127
						1135	ggguagaagugguuauaca	11112	1358	gguacauuauugggcaauu	11128
1152	cagugcacguacagugcaa	11113	1359	guacauuauugggcaauuu	11129
						1183	ccaccaggguacacuacua	11114	1457	ccaauggauucuaugguua	11130
1189	ggguacacuacuagugguu	11115	1483	caauuggaguuugguaaua	11132
						1191	guacacuacuagugguuau	11116	1657	gacaacagaugauaugcaa	11142
1214	ccagaacaccaguuagcua	11117	1703	ccaacaaaagagaucuuua	11143
						1222	ccaguuagcuacaguaaau	11118	1725	caggggagguuaagaacuu	11145
1225	guuagcuacaguaaauaaa	11119	1733	guuaagaacuugauugaaa	11146
						1229	gcuacaguaaauaaaggua	11120	1748	gaaaugugucagguggaua	11147
1230	cuacaguaaauaaagguaa	11121	1760	guggauacacucauaccaa	11148
						1235	guaaauaagguaauguuua	11122	1916	gagauagcaaguuacuuua	11154
1245	guaauguuaaugcagguua	11123	1922	gcaaguuacuuuacacacu	11155
						1300	ggguacacaaguugaaaau	11124	1941	ggacagggagccugcgauu	11156
1321	gaaacaaccuaguggaugau	11125	1954	gcgauucaguuucauguuu	11157
						1334	gaugauaauuggcuaaauu	11126	1980	cugcaaacacuaccuuaaa	11158
1345	gcuaaauuuugaugguaca	11127	2024	gggauugguaagccuagaa	11159
						1358	gguacauuauugggcaauu	11128	2035	gccuagaguagaaagggaa	11161
1359	guacauuauugggcaauuu	11129	2040	gaaguagaaaggaagcaau	11162
						1457	ccaauggauucuaugguua	11130	2043	guagaaaggaagcaauguuu	11163

1463	gauucuaugguuaggcaua	11131	2064	ggacacacgugguguggga	11165
						1483	caauuggaguuugguaaua	11132	2074	ggugugggauguagguuua	11166
1495	gguaauaauaccguuuugu	11133	2122	gaucagugccagucaguau	11168
						1514	caacuacaaagcaacaaua	11134	2176	cuacauuacaugcugguau	11169
1517	cuacaaagcaacaauauau	11135	2289	gagacacagaccugcacaa	11171
						1524	gcaacaauauauccaacau	11136	2338	ggaaagauauguagaugaa	11175
1525	caacaauauauccaacauu	11137	2356	agucuuaaaugaaguguua	11176
						1566	gcccaaugugugcugaauu	11138	2441	gaaacaggacauaccaaua	11178
1585	cucuggagcacgugccaaa	11139	2515	ggaugaaaugaguguggaa	11183
						1610	gugcaaggucuaccaguau	11140	2516	gaugaaaugaguguggaaa	11184
1612	gcaaggucuaccaguauau	11141	2530	ggaaagcuuccuaggcaga	11185
						1657	gacaacagaugauaugcaa	11142	2629	gcaagaaauggcacaaauu	11192
1703	ccaacaaaagagaucuuua	11143	2630	caagaaauggcacaaauua	11193
						1717	cuuuauaccaggagagguu	11144	2638	ggcacaaauuagaagaaaa	11194
1725	caggagagguuaagaacuu	11145	2639	gcacaaauuagaagaaaau	11195
						1733	guuaagaacuugauugaaa	11146	2675	gcaagauuugacucugaaa	11197
1748	gaaaugugucagguggaua	11147	2804	gcuuggcaaucuggaacaa	11203
						1760	guggauacacucauaccaa	11148	2816	ggaacaaaugcaucuguau	11204
1762	ggauacacucauaccaaua	11149	2817	gaacaaaugcaucuguauu	11205
						1842	caaaauuagcugaagaaau	11150	2881	gaguauugcaucagcauau	11206
1851	cugaagaaauuuuugcaau	11151	2892	cagcauauuacaugtuuua	11207
						1853	gaagaaauuuuugcaauua	11152	2961	ccaaugacaugggaacuuu	11210
1899	ccacaacccucauugguga	11153	3033	ggauauaucacaaagccaa	11217
						1916	gagauagcaaguuacuuua	11154	3034	gauauaucacaaagccaaa	11218
1922	gcaaguuacuuuacacacu	11155	3047	gccaaacacaccaaagcuu	11219
						1941	ggacagggagccugcgauu	11156
1954	gcgauucaguuuuauguuu	11157
						1980	cugcaaacacuaccuuaaa	11158
2024	gggauugguaagccuagaa	11159
						2030	gguaagccuagaaguagaa	11160
2035	gccuagaaguagaaaggaa	11161
						2040	gaaguagaaaggaagcaau	11162
2043	guagaaaggaagcaauguu	11163
						2050	ggaagcaauguuagggaca	11164
2064	ggacacacgugguguggga	11165
						2074	ggugugggauguagguuua	11166
2080	ggauguagguuuacaaucu	11167
						2122	gaucagugccagucaguau	11168
2176	cuacauuacaugcgguuau	11169
						2232	cuugcugaguguuguguuu	11170
2289	gagacacagaccugcacaa	11171
						2302	gcacaagcaaacaggacca	11172
2305	caagcaaacaggacaaaua	11173
						2308	gcaaacaggaccaaaaaca	11174
2338	ggaaagauauguagaugaa	11175
						2356	agucuuaaaauugaaguua	11176
2382	ccaauauuaaucagagcca	11177
						2441	gaaacaggacauaccaaua	11178

2454	ccaauaagauacagccaga	11179
						2467	gccagaagacacuauagaa	11180
2468	ccagaagacacuauagaaa	11181
						2495	gugcaaucuucacagacau	11182
2515	ggaugaaugagugugggaa	11183
						2516	gaugaaaugaguguggaaa	11184
2530	ggaaagcuuccuaggcaga	11184
						2561	caugaaucaguguuggaua	11186
2584	ggacaauuacaaugaucaa	11187
						2597	gaucaaaguuucacuaaau	11188
2616	ggaacauaaaccugcaaga	11189
						2617	gaacauaaaccugcaagaa	11190
2619	acauaaaccugcaagaaau	11191
						2629	gcaagaaauggcacaaauu	11192
2630	caagaaauggcacaaauua	11193
						2638	ggcacaaauuagaagaaaa	11194
2639	gcacaaauuagaagaaaau	11195
						2649	gaagaaaauuugaaauguu	11196
2675	gcaagauuugacucugaaa	11197
						2735	ggucauauagucaugcaau	11198
2736	gucauauagucaugcaaua	11199
						2738	cauauagucaugcaauaua	11200
2774	gcaccuauaccaacaacua	11201
						2784	caacaacuagagaugacua	11202
2804	gcuuggcaaucuggaacaa	11203
						2816	ggaacaaaugcaucuguau	11204
2817	gaacaaaugcaucuguauu	11205
						2881	gaguauugcaucagcauau	11206
2892	cagcauauuacauguuuua	11207
						2916	guuaugauggagacacaua	11208
2924	ggagacacauauaaaucca	11209
						2961	ccaaugacaugggaacuuu	11210
2972	ggaacuuuguguucgcgua	11211
						2997	ccagugagcaauuacacaa	11212
2998	cagugagcaauuacacaaa	11213
						3004	gcaauuacacaaagucaaa	11214
3010	acacaaagucaaaguggua	11215
						3019	caaagugguaacaaggaua	11216
3033	ggauauaucacaaagccaa	11217
						3034	gauauaucacaaaggcaaa	11218
3047	gccaaacacaccaaagcuu	11219
						3086	gcuguucaauacucacaua	11220
3092	caauacucacauacacaua	11221
						3118	cuacaaauugaguucagaa	11222
3121	caaauugaguucagaagua	11223
						3151	ggcuauaagaccuagaaca	11224
3152	gcuauaagaccuagaacaa	11225
						3153	cuauaagaccuagaacaaa	11226

3161	ccuagaacaaaucuaacaa	11227
						3199	guaugugcauguugguaau	11228
3205	gcauguugguaaucuaaua	11229
						3212	gguaaucaauaauacagaa	11230
3213	guaaucuaauauacagaaa	11231

体外分析

在人类Hela细胞中测试siRNA对鼻病毒感染的效力。Hela细胞生长于补充10％胎牛血清(FBS)和1％Pluronic F-68，带有Earle’s Salt的MEM中。以人类鼻病毒16的母液在200噬菌斑形成单位(PFU)/ml感染细胞。受感染的细胞培育1小时以允许病毒吸附至细胞。培育后以siRNA分子转染细胞。Dharmacon的Sicontrol用作对照siRNA。转染后在合适的时间点收集细胞，收集上清液，以实时PCR检测病毒复制(13)。使用实时PCR中的病毒非靶基因特异性引物(如聚合酶)来测量病毒复制的减少。上清液用于对Hela细胞单层进行病毒噬菌斑检测(14)。我们还计划根据上述方法首先转染细胞，然后以人类鼻病毒16感染以研究其对抑制病毒复制的效力。

实施例28.产生和测试衍生自轮状病毒的siRNA

使用上述方法或从公众可获得的序列鉴别轮状病毒核蛋白。使用上述方法从编码轮状病毒核蛋白的核酸中鉴别siRNA。

表31列出了作为siRNA轮状病毒(VP6)核蛋白靶序列的19-核苷酸区。所提供的19核苷酸区作为设计多种siRNA分子的有义链是有用的，该分子任选地在有义链和反义链中的任一条或两条都具有不同的3，突出端。因此，本领域技术人员将明白，从表31所列每条序列可获得大量有义和反义siRNA。

表31.轮状病毒VP6
						5’核苷酸位置	靶序列	SEQIDNO	5’核苷酸位置	保守靶序列	SEQ IDNO
20	cgacauggagguucuguac	11232	54	cuuaaagaugcuagggaca	11233
						54	cuuaaagaugcuagggaca	11233	163	agacuggaggaauugguaa	11234

163	agacuggaggaauugguaa	11234	567	cuuaaugcuggaucagaaa	11242
						168	ggaggaauugguaauuuac	11235	588	caaguggcuggauuugacu	11243
213	ggucuauuagguacaacac	11236	975	gcaacaguuggacuuacau	11250
						236	gaacuuggaugcuaauuau	11237	1137	acuaacuauucaccaucua	11255
258	gagaaugcaagaacuauaa	11238	1182	acgguagcuuccauuagaa	11257
						314	ggaugaaauggcaagagaa	11239	1283	cuucaaguaaggacaugau	11260
315	gaugaaauggcaagagaau	11240
						556	gaaccauguggcuuaaugc	11241
567	cuuaaugcuggaucagaaa	11242
						588	caaguggcuggauuugacu	11243
604	acuacucaugcgccauaaa	11244
						605	cuacucaugcgccauaaau	11245
631	cgaacauacagcaauuuga	11246
						846	gcuagauuugguacuauca	11247
856	cuuaaagaugcuagggaca	11233
						903	uugaugcguccaccuaaua	11248
904	ugaugcguccaccuaauau	11249
						975	gcaacaguuggacuuacau	11250
981	guuggacuuacauuacgua	11251
						1064	cgcggugcgucaagaauau	11252
1113	ggcaugaauuggacugaau	11253
						1114	gcaugaauuggacugaauu	11254
1137	acuaacuauucaccaucua	11255
						1181	cacgguagcuuccauuaga	11256
1182	acgguagcuuccauuagaa	11257
						1192	ccauuagaagcauguugau	11258
1242	caaucuuaguuagcaugua	11259
						1283	cuucaaguaaggacaugau	11260

体外分析

恒河猴肾细胞系MA104用于在组织培养中繁殖病毒并制备大的病毒母液。以各种浓度的不同siRNA转染之前或之后，优化剂量的病毒感染MA104细胞。Dharmacon的Sicontrol用作对照siRNA。转染后在合适的时间点收集细胞，以两次冷冻-解冻循环裂解，裂解物以10ug/ml的胰岛素在37℃处理30分钟。如Pando等所述的免疫过氧化物酶焦点检测来确定病毒制品的感染效价(15)。

在轮状病毒感染的小鼠模型中评价siRNA对轮状病毒体内复制的效力。对小鼠静脉给药2-10mg/kg剂量的修饰或未修饰siRNA，带有或不带有制品。Dharmacon的Sicontrol以同样剂量给药。在给药siRNA之前或之后，口饲给予小鼠优化剂量的轮状病毒。在合适的时间点，例如病毒接种2天后，对每只小鼠的末端结肠检测亮黄色液体成分的存在，这是轮状病毒-诱导腹泻的特征，并收集完整肠道以经由酶免疫检测或RT-PCR对轮状病毒抗原定量。

实施例29.体外siRNA介导的人类鼻病毒复制的抑制

本实施例证明本发明的示例性siRNA分子在体外有效抑制人类鼻病毒(HRV)的复制。筛选了33种siRNA(序列见表32)抑制大或小ATCC(美国典型培养物保藏中心)HRV的能力。被选择以靶向HRV的33siRNA代表HRV基因组的“保守”区。通过分析可得的Genbank HRV核苷酸序列并由比对推断这些序列中的“保守”区而选择这些siRNA。最初以33siRNA中的一种转染Ohio Hela-I细胞(OH-I细胞)，然后感染两种不同人类鼻病毒血清型中的一种而进行筛选。以TICD₅₀(组织培养感染剂量)检测来测量病毒产率的减少，该检测统计活病毒。TICD₅₀值的减少表示活病毒群体减少，以及病毒复制的减少。在本实施例中，TICD₅₀大的减少表示更有效抑制病毒复制的siRNA。

表32.靶向人类鼻病毒的33siRNA的核苷酸序列

病毒靶序列中siRNA的5’核苷酸位置	siRNA核苷酸序列		HRV靶序列
				632	gcucaaguaucuagacaga	(SEQ ID NO：11088)	VP4
840	guguagaagcuuguggaua	(SEQ ID NO：11095)	VP2
				1079	ccagaugcucuuaaagaca	(SEQ ID NO：11107)	VP2

1085	gcucuuaaagacaugggua	(SEQ ID NO：11108)	VP2
				1086	cucuuaaagacauggguau	(SEQ ID NO：11109)	VP2
1088	cuuaaagacauggguauuu	(SEQ ID NO：11110)	VP2
				1099	ggguauuuuuggugaaaau	(SEQ ID NO：11111)	VP2
2639	gcacaaauuagaagaaaau	(SEQ ID NO：11195)	VP1
				2675	gcaagauuugacucugaaa	(SEQ ID NO：11197)	VP1
2676	caagauuugacucugaaau	(SEQ ID NO：11261)	VP1
				3033	ggauauaucacaaagccaa	(SEQ ID NO：11217)	VP1
3034	gauauaucaacaagccaaa	(SEQ ID NO：11218)	VP1
				3047	gccaaacacaccaaagcuu	(SEQ ID NO：11219)	VP1
4231	gaagagaagugaaccugua	(SEQ ID NO：11262)	P2-C
				4356	cuaaauuauuugaugguua	(SEQ ID NO：11263)	P2-C
6344	ccagaaaccuuuuggucua	(SEQ ID NO：11264)	Pol
				6390	gcaucauggcuuuugauua	(SEQ ID NO：11265)	Pol
174	cucuuuuuucaaaauacaa	(SEQ ID NO：11266)	Pol
				178	uuuuucaaaauacaaaggu	(SEQ ID NO：11267)	Pol
181	uucaaaauacaaagguaac	(SEQ ID NO：11268)	Pol
				627	gugcaguuggaugugaucc	(SEQ ID NO：11269)	Pol
950	gauuuagauaaacuuaaaa	(SEQ ID NO：11270)	Pol
				951	auuuagauaaacuuaaaau	(SEQ ID NO：11271)	Pol
1196	gaguccauuagauggacaa	(SEQ ID NO：11272)	Pol
				1197	aguccauuagauggacaaa	(SEQ ID NO：11273)	Pol
	gaauguggcuaaccuuaaa	(SEQ ID NO：11274)	5’UTR
					gaaugcggcuaaccuuaaa	(SEQ ID NO：11275)	5’UTR
	gaauguggcuaauccuaaa	(SEQ ID NO：11276)	5’UTR
					cugaauguggcuaaccuua	(SEQ ID NO：11277)	5’UTR
	ugaauguggcuaaccuuaa	(SEQ ID NO：11278)	5’UTR
					gaccaacuacuuugggugu	(SEQ ID NO：11279)	5’UTR
	ggaccaacuacuuugggug	(SEQ ID NO：11280)	5’UTR
					gggaccaacuacuuugggu	(SEQ ID NO：11281)	5’UTR

对该研究，测试了两种HRV血清型：HRV16型和HRV1A型，HRV16型属于大受体组，该组包括90％的101个HRV血清型并使用ICAM-1细胞表面受体以进入细胞，HRV1A型属于小受体组并使用低密度脂蛋白受体超家族的几个成员以进入细胞。评价了33siRNA对两种鼻病毒血清型HRV16型和HRV1A型病毒产率的抑制效应。所有siRNA构建体都在使用前以5pmol/μl的浓度贮存于-70℃。本实施例中，普来可那立和ruprintrivir用作阳性对照，已知它们能有效抑制病毒复制。普来可那立以1μg或10μg的浓度施用，而ruprintrivir以0.1μg的浓度施用。Dharmacon^TM的Sicontrol用作阴性对照siRNA。还进行无siRNA转染的病毒感染，作为对照(标为“病毒对照1”、“病毒对照2”等等)。

最初进行对照试验以优化转染步骤(即，细胞数目和伴随siRNA的Lipofectamine^TM2000(Invitrogen)浓度)和感染步骤(即，Lipofectamine^TM2000对鼻病毒复制的影响)。为了优化转染步骤，对两个24-孔板上的孔接种75,000或100,000 OH-I细胞/孔。确定了各种浓度Lipofectamine^TM 2000(1μl/孔、1.4μl/孔、或1.8μl/孔)对阳性siRNA对照降解靶转录子效力的负向影响(沉默程度)。还使用了阴性siRNA对照。转染后从细胞提取RNA，进行RT-PCR。还使用实时PCR以确定接种75,000和100,000 OH-I细胞/孔的两个24-孔板在转染期间的沉默程度。如预期的，该结果表示较少细胞数目的发生较多沉默。因此，本实施例中的转染以大细胞数目进行(100,000 OH-I细胞)。

为了优化感染步骤，对两个24-孔板上的孔接种50,000；75,000或100,000 OH-I细胞/孔。一个24-孔板上的细胞以10 TICD₅₀的HRV-16感染，另一个板上的细胞以180 TICD₅₀的HRV-16感染。3种不同接种的细胞数目群体接受0μl、1μl、1.4μl、或1.8μl Lipofectamine^TM 2000。感染后24、48和72小时收集样品以测量病毒产率。24小时时，在所有情形(有或无Lipofectamine^TM2000)，较低的病毒接种(10 TICD₅₀)与较高的(180 TICD₅₀)相比产生低的滴度。48小时时，在所有情形中，两种病毒接种与感染24小时后相比产生较高的病毒产率。没有Lipofectamine时，结果表示在所测量的细胞数目范围内，细胞数目不影响病毒产率。带有Lipofectamine浓度的在感染后24、48和72小时测量的病毒产率不影响HRV感染或生长。从以上结果，本实施例描述的随后的感染以低病毒接种(10 TICD₅₀)进行，并在1.4μl/孔的Lipofectamine^TM 2000进行转染。

转染如下进行：首先，将24-孔板接种100,000 OH-I细胞/ml/孔，培养于添加了5％胎牛血清、5％胎克隆血清、1％L-谷氨酰胺和抗生素的Eagle’s最低必需培养基(EMEM)。在37℃、5％CO₂培养箱中将细胞培养过夜。siRNA转染时的细胞层融合为大约50-60％。第二，过夜培养后，制备对每种siRNA的工作Lipofectamine^TM 2000(LF2K)母液。这些母液在96-孔板中制备，然后施加该溶液至24-孔板上的OH-I细胞。每种LF2K母液的总体积为50μl/孔并包括1.4μl的LF2K和48.6μl的Optimem；轻柔搅动该溶液并置于冰上直至使用。第三，向96-深-孔板的A、C和E排的每孔加入200μl的LF2K-Optimem稀释液。向B、D和F排的每孔加入180μl的Optimem。搅动siRNA溶液，短暂地在微离心管中旋转，然后置于冰上。每种siRNA的20μl样品加入至96-深-孔板的B、D和F排的合适孔，上下吸液三次而轻柔混合。因此，在转染步骤的此时间点，B、D和F排的孔具有200μl的体积(180μl Optimem+20μl siRNA溶液)。然后将A排孔中的液体转移到B排的相应孔，将C排孔中的液体转移到D排的相应孔，将E排孔中的液体转移到F排的相应孔。转移液体的结果是在B、D和F排的孔中产生siRNA-LF2K混合物。从每排转移液体后，上下吸液五次而混合各孔(吸液管头例行地更换以避免交叉污染)。然后紧密地盖上96-深-孔板，室温下培养30分钟。最后，培养30分钟后，从培养箱移出带有OH-I细胞的24-孔板，从所有孔吸去培养基。无抗生素的10％EMEM的400μl样品加至各孔，然后加入100μl siRNA-LF2K混合物。每种siRNA测试三份，因此24-孔板上的三个不同孔接受含有同样siRNA的100μlsiRNA-LF2K混合物。在37℃、5％CO₂培养转染板(24-孔板)5小时。

5小时转染培养后，从所有孔吸去所有培养基，各不同siRNA-LF2K混合物质间更换吸液管头以避免交叉污染。然后以两种HRV血清型中的任一种感染细胞，通过加入100μl 2×病毒(对HRV-16稀释10⁶，对HRV-1A稀释10^5.5)和100μl无抗生素或MgCl₂的2％McCoy’s至各孔。在34℃，病毒与OH-I细胞一起培养1小时。然后从各孔吸去病毒培养基，以Hanks平衡盐溶液(HBSS)漂洗所有孔两次，重新补充1.5ml带有抗生素和MgCl₂的2％McCoy’s。只接受普来可那立或ruprintrivir的24-孔板上的孔重新补充750μl 2×药物和750μl 2％McCoy’s并在34℃培养24小时。上清液总体积为每孔1.5ml。普来可那立或ruprintrivir培养的细胞不转染siRNA。

转染后24、48和72小时，从代表每种siRNA和对照的各孔收集400μl上清液样品，并集中用于之后的滴定。样品贮存于-70℃。对24和72小时收集物制备系列10倍稀释液，以四份滴定(每稀释液4个孔，每孔100μl)。滴定的样品与OH-I细胞一起培养于96-孔板。7天的时段后，观察到OH-I细胞的细胞病变效应(CPE)。对24小时收集物测试10⁰至10⁵的稀释液，对72小时收集物测试10⁰至10⁷的稀释液。收集用于病毒产率减少检测的病毒被冷冻，进行返滴定以确定接种物的TICD₅₀；靶接种物为每单层10至32 TICD₅₀。

结果概述于表33、34、35。表33概述了转染到OH-I细胞的siRNA 1至25并随后用HRV-16血清型感染的数据。表34概述了转染到OH-I细胞的siRNA 1至25并随后用HRV-1A血清型感染的数据。表35概述了转染到OH-I细胞的siRNA 21和24至33并随后用HRV-16血清型或HRV-1A血清型感染的数据。表33和34所示的数据通常分为4个不同组。每组代表siRNA的一个子集，该子集一起经历转染和感染步骤，并结合对照(即，病毒对照1与组1，病毒对照2与组2，等等)。每组经历同样的转染和感染步骤，具有同样的病毒对照。这些组的区别仅在于，每组所测试siRNA子集不是一起测试的。每组的病毒对照用作比较的基线，以确定组中的siRNA是否减少病毒复制。类似地，表35所示的数据通常分为4个不同组，每组由细双线分开。表35中的四组标记为与表33和34中的四组完全不关联。表35中的四组表示为病毒对照和所用HRV血清型。例如，一组含有“病毒对照1”和HRV16血清型。

达到了10和32 TICD₅₀之间的TICD₅₀。在所有情形，阳性对照普来可那立和ruprintriVir与病毒对照相比是抑制的，且在24小时减少2 log₁₀或更多，在72小时超过5 log₁₀。对本实施例，当与病毒对照相比减少病毒滴度超过1.0 log₁₀时，认为siRNA显著的减少病毒产率。更高的减少很可能表示特异性抑制。对所测试的针对HRV-16的33siRNA，与病毒对照相比，在24小时时6种siRNA(10、13、14、1 5、17和1 8)表示出病毒产率的显著减少(1.5至1.75 log₁₀/ml)(表33和35)。在72小时时12种siRNA(7至17和19)减少病毒滴度1.5至2.0 log₁₀/ml，1种siRNA(1 8)减少病毒滴度2.5 log₁₀。

对所测试的针对HRV-1A的33种构建体，与病毒对照相比，在24小时时2种siRNA(7和8)表示出滴度的1.25 log₁₀减少(1.5至/ml)，在72小时时2种siRNA(4和5)分别减少病毒滴度1.5和1.75 log₁₀(表34和35)。而且，在72小时时6号siRNA减少病毒滴度1.25 log₁₀。对所测试的其它siRNA，证明没有对HRV-16或HRV-1A的实质抑制。

表33.siRNA介导的对人类鼻病毒-16滴度的体外减少

测试组	siRNA或对照	人类鼻病毒-16(10TCID50)
				24小时收集物    /0.1ml	72小时收集物   /0.1ml
		组l	病毒对照1			2.25	6.75
siRNA 1	1.75			6.0
			siRNA2		1.25	6.25
siRNA3	1.50			6.25
			siRNA4		1.50	6.0
siRNA5	2.50			6.25
			siRNA6		1.75	≥6.5
sicontrol	2.5			≥6.5
			组2		病毒对照2	2.25	7.25
普来可那立1μg		
				siRNA7	1.75	5.5
siRNA8	1.25	5.75
				siRNA9	1.25	5.25
siRNA10	0.5	5.5
				siRNA11	1.5	5.25
siRNA12	1.50	5.5
				组3	病毒对照3	2.5	7.75
siRNA13	1.0	6.0
			siRNA14		0.75	5.75
siRNA15	0.75	6.25
			siRNA16		2.0	6.25
siRNA17	0.75	5.75
			siRNA18		1.0	5.25
siRNA19	2.25	6.25
			组4		病毒对照4	1.5	7.0
siRNA20	1.5	6.25
				siRNA21	1.5	≥6.5
siRNA22	2.0	625
				siRNA23	2.0	≥6.5
siRNA24	2.50	≥6.5
				siRNA25	2.75	≥6.5

病毒对照是无siRNA转染的病毒感染细胞。

表34.siRNA介导的对人类鼻病毒-1A滴度的体外减少

测试组	siRNA或对照	人类鼻病毒-1A    (32 TCID50)
				24小时收集物  /0.1ml	72小时收集物 /0.1 ml
		组1	病毒对照1			1.0	7.25
siRNA1	1.25			6.25
			siRNA2		2.25	6.75
siRNA3	1.25			6.75
			siRNA4		1.50	5.75
siRNA5	0.5			5.50
			siRNA6		1.25	6.0
sicontrol	1.50			7.25
			组2		病毒对照2	1.75	6.25
普来可那立10μg		0.75
				siRNA7	0.5	6.25
siRNA8	0.5	6.25
				siRNA9	1.5	6.0
siRNA10	2.0	6.25
				siRNA11	1.75	5.75
siRNA12	1.75	6.75
				组3	病毒对照3	1.0	6.5
siRNA13	1.75	6.75
			siRNA14		1.50	6.75
siRNA15	1.25	6.25
					siRNA16	1.75	7.0
siRNA17	1.75	6.50
				siRNA18	1.25	6.25
Ruprintrivir.0.1μg		1.5
				组4	病毒对照4	1.0	7.0
siRNA19	1.50	6.75
			siRNA20		1.75	7.0
siRNA21	未检测	未检测
			siRNA22		2.0	6.75
siRNA23	2.25	6.75
			siRA24		未检测	未检测
siRNA25	未检测	未检测

表35.siRNA介导的对人类鼻病毒-1A或人类鼻病毒-16滴度的体外减少

siRNA或对照	人类鼻病毒-16 (32TCID50)		siRNA或对照	人类鼻病毒-1A (32TCID50)
						24小时收集物/0.1 ml	72小时1收集物/0.1 ml	24小时收集物/0.1ml	72小时收集物/0.1 ml
	病毒对照1	2.0		7.0	病毒对照1					2.0	6.25
siRNA21			1.25			6.75	siRNA21	2.5	6.75
	siRNA24	1.75		6.5	siRNA24					2.0	6.25
siRNA25			1.75			6.75	siRNA25	2.5	6.75
	siRNA26	3.0		6.75	siRNA26					2.0	6.5
siRNA27			2.5			7.25	siRNA27	1.75	6.75
	siRNA28	2.0		6.75	siRNA28					2.25	6.5
普来可那立1μg							普来可那立10μg		0.75
	病毒对照2	2.5		7.5	病毒对照2					2.50	6.5
siRNA29			2.25			7.25	siRNA29	1.5	6.5
	siRNA30	2.5		6.75	siRNA30					2.0	7.0
siRNA31			2.0			7.0	siRNA31	2.0	7.0
	siRNA32	2.0		6.75	siRNA32					2.5	6.0
siRNA33			2.25			6.75	siRNA33	2.25	6.5
	sicontrol	2.75		7.0	siRNA对照					2.5	6.5
Ruprintrivir0.1μg						1.25	Ruprintrivir0.1μg		0.5

总之，两种阳性对照1μg的普来可那立和10μg的ruprintrivir如所预期的在24小时和72小时显著抑制HRV的两种血清型。与病毒对照相比，在24小时时siRNA 10、13-15、17和1 8，在72小时时siRNA 7至19减少HRV-16病毒滴度至少1.0 log₁₀。与病毒对照相比，在24小时时siRNA7和8，在72小时时siRNA 4至6减少HRV-1A病毒滴度至少1.0 log₁₀。

表33、34和35的数据表示选择的siRNA能在体外有效减少人类鼻病毒的病毒复制。

实施例30.体外siRNA介导的人类偏肺病毒RNA的降解

本实施例证明本发明的示例性siRNA分子在体外显著减少人类偏肺病毒(hMPV)靶转录子(RNA)的RNA拷贝数。特定病毒转录子的病毒RNA拷贝数的减少与病毒复制减少相关联。因此，病毒复制减少使得新病毒颗粒的生成最少和/或阻止新病毒颗粒的生成，因此减少或抑制再次感染并使得患者病毒诱导的病理最少。

本实施例描述了以双-萤光素酶检测进行最初筛选200siRNA以鉴别有效减少靶RNA水平的siRNA，如由花虫萤光素酶活性减少而间接测量的。而且本实施例描述了对从最初筛选的200siRNA选择的57种鉴别的siRNA的第二筛选，以进一步表征有效减少靶hMPV RNA水平的那些siRNA。

下表36描述了接受最初双-萤光素酶检测筛选的200siRNA。选择以靶向hMPV RNA的200siRNA代表以下一种hMPV基因的“保守”区：N基因、P基因、M基因、F基因、M2-1基因、M2-2基因、或L基因。通过分析hMPV基因组可得的Genbank核苷酸序列(登记号#AY297748.1)并由比对推断这些序列中的“保守”区而选择这些siRNA。对最初筛选，每种siRNA以10 nM浓度三份地检测。

表36.双-萤光素酶检测筛选的siRNA的核苷酸序列

siRNA#	病毒靶序列中siRNA的5’核苷酸位置	siRNA核苷酸序列		hMPV靶基因
					1	60	cuucaagggauucaccuaa	(SEQ ID NO：10885)	N
2	74	ccuaagugaucugucauau	(SEQ ID NO：10886)	N
					3	75	cuaagugaucugucauaua	(SEQ ID NO：10887)	N
4	86	gucauauaaacaugcuaua	(SEQ ID NO：10888)	N
					5	88	cauauaaacaugcuauauu	(SEQ ID NO：10889)	N
6	111	gagucucaauacacaauaa	(SEQ ID NO：10890)	N
					7	122	cacaauaaaaagagaugua	(SEQ ID NO：10891)	N
8	174	cagcaagagauaacacuuu	(SEQ ID NO：10894)	N
					9	198	ggagagauucuuuacacua	(SEQ ID NO：10895)	N
10	199	gagagauucuuuacacuaa	(SEQ ID NO：10896)	N
					11	214	cuaaacauacugauuacaa	(SEQ ID NO：10897)	N
12	240	gcagagauagggauacaau	(SEQ ID NO：10899)	N
					13	241	cagagauagggauacaaua	(SEQ ID NO：10900)	N
14	243	gagauagggauacaauaua	(SEQ ID NO：10901)	N
					15	245	gauagggauacaauauauu	(SEQ ID NO：10902)	N
16	249	gggauacaauauauuugca	(SEQ ID NO：10903)	N
					17	269	ggcucuaggaucagaaaga	(SEQ ID NO：10904)	N
18	280	cagaaagaguacaacagau	(SEQ ID NO：10905)	N
					19	282	gaaagaguacaacagauuu	(SEQ ID NO：10906)	N
20	288	guacaacagauuuuaagaa	(SEQ IDNO：10907)	N
					21	383	guugcaaauguuagauaua	(SEQ ID NO：10920)	N
22	386	gcaaauguuagauauacau	(SEQ ID NO：10921)	N
					23	396	gauauacauggaguggaaa	(SEQ ID NO：10922)	N
24	416	gaguuggguagaagaaaua	(SEQ ID NO：10924)	N
					25	421	ggguagaagaaauagacaa	(SEQ ID NO：10925)	N
26	422	gguagaagaaauagacaaa	(SEQ ID NO：10926)	N
					27	429	gaaauagacaaagaggcaa	(SEQ ID NO：10927)	N
28	435	gacaaagaggcaagaaaaa	(SEQ ID NO：10928)	N
					29	467	gcuaaaggaaucaucaggu	(SEQ ID NO：10933)	N
30	468	cuaaaggaaucaucaggua	(SEQ ID NO：10934)	N
					31	481	cagguaacaucccacaaaa	(SEQ ID NO：10935)	N
32	506	gccuucagcaccagacaca	(SEQ ID NO：10938)	N
					33	513	gcaccaggacacacaauaa	(SEQ ID NO：10939)	N
34	514	caccagacacaccaauaau	(SEQ ID NO：10940)	N

35	516	ccagacacaccaauaauuu	(SEQ ID NO：10941)	N
					36	562	cuaaacuagcaucaacaau	(SEQ ID NO：10944)	N
37	588	ggacuagagacuacaguua	(SEQ ID NO：10945)	N
					38	663	ccgaagauugcuagaucuu	(SEQ ID NO：10951)	N
39	676	gaucuuucuaugaacuauu	(SEQ ID NO：10952)	N
					40	715	ggagucuauucauugagua	(SEQ ID NO：10954)	N
41	716	gagucuauucauugaguau	(SEQ ID NO：10955)	N
					42	735	gggaaagcuuuaggcucau	(SEQ ID NO：10956)	N
43	741	gcuuuaggcucaucuucaa	(SEQ ID NO：10957)	N
					44	747	ggcucaucuucaacaggaa	(SEQ ID NO：10958)	N
45	763	gaagcaaagcagaaaguuu	(SEQ ID NO：10959)	N
					46	778	guuuguuuguaaauauauu	(SEQ ID NO：10960)	N
47	816	ggucaaacaaugcuaaggu	(SEQ ID NO：10966)	N
					48	846	gccagaucaucuaacaaca	(SEQ ID NO：10968)	N
49	847	ccagaucaucuaacaacau	(SEQ ID NO：10969)	N
					50	850	gaucaucuaacaacauaau	(SEQ IDNO：10971)	N
51	860	caacauaaugcuaggacau	(SEQ ID NO：10972)	N
					52	891	gcugaauugaagcaaguua	(SEQ ID NO：10974)	N
53	953	gcuuuuacaucuaagacaa	(SEQ ID NO：10979)	N
					54	1038	gcuucaggucuagguauaa	(SEQ ID NO：10980)	N
55	1104	gcagaaaaguaugccagaa	(SEQ ID NO：10983)	N
					56	1116	gccagaagcuuaaaagaaa	(SEQ ID NO：10984)	N
57	1123	gcuuaaaagaaagcaacaa	(SEQ ID NO：10985)	N
					58	1163	gcucacagacgaagaaaaa	(SEQ ID NO：10986)	N
59	1297	ggguaaugaagcagcaaaa	(SEQ ID NO：11282)	P
					60	1319	gcagaagcuuuccagaaau	(SEQ ID NO：11283)	P
61	1380	gggaaaaaguaaacacuau	(SEQ ID NO：11284)	P
					62	1381	ggaaaaaguaaacacuaua	(SEQ ID NO：11285)	P
63	1699	gcucucagacaaugaggaa	(SEQ ID NO：11286)	P
					64	1724	gcagaguccucaaucuuaa	(SEQ ID NO：11287)	P
65	1780	ggcuagacuagaaucaaua	(SEQ IDNO：11288)	P
					66	1898	gguauaagagaagaacuaa	(SEQIDNO：11289)	P
67	1963	ggaagaggaaaugaaucaa	(SEQ ID NO：11290)	P
					68	2017	cgagaaggcaaaagaacuu	(SEQ ID NO：11291)	P
69	2104	ggauaacaaucaaggagaa	(SEQ ID NO：11292)	P
					70	2196	ggacacuuaucaaggcauu	(SEQ IDNO：11293)	M
71	2431	cccaaaaaauucgaaguaa	(SEQ ID NO：11294)	M
					72	2432	ccaaaaaauucgaaguaaa	(SEQ ID NO：11295)	M
73	2542	ccauaugggauggugucaa	(SEQ ID NO：11296)	M
					74	2576	ccaaaucaguuggcaacaa	(SEQ ID NO：11297)	M
75	3071	ggaaagugaugauuaucau	(SEQ ID NO：11298)	F
					76	3115	ggacuaaaggaaaguuauu	(SEQ ID NO：11299)	F
77	3430	gcgauagccaaaaccauaa	(SEQ ID NO：11300)	F
					78	3449	ggcuugagagugaagugaa	(SEQ ID NO：11301)	F
79	3589	gcaauuaacaagaacaaau	(SEQ ID NO：11302)	F
					80	3631	gcugucagcuucagucaau	(SEQ ID NO：11303)	F
81	3697	gggauaacaccagcaauau	(SEQ ID NO：11304)	F
					82	3709	gcaauaucauuggaccuaa	(SEQ ID NO：11305)	F

83	3818	ggagaaaaggauuuggaau	(SEQ ID NO：11306)	F
					84	3928	gcucccucuuguucagaaa	(SEQ ID NO：11307)	F
85	4010	ccacuguuuacuacccaaa	(SEQ ID NO：11308)	F
					86	4093	gcugagcaaucaagagaau	(SEQ ID NO：11309)	F
87	4154	gcacaggaagacacccuau	(SEQ ID NO：11310)	F
					88	4356	gggugaacagcauguaaua	(SEQ ID NO：11311)	F
89	4522	ggaaacacuggcuucauua	(SEQ ID NO：11312)	F
					90	4589	gcaucaucaucauaaucaa	(SEQ ID NO：11313)	F
91	4673	cgcauaguuaguuaauuaa	(SEQ ID NO：11314)	F
					92	4674	gcauaguuaguuaauuaaa	(SEQ ID NO：11315)	F
93	4716	cguaaagcuccaugcaaau	(SEQ ID NO：11316)	M2-1
					94	4771	gcaaauucaaccacaauua	(SEQ ID NO：11317)	M2-1
95	4993	gcuauagucuacauaacau	(SEQ ID NO：11318)	M2-1
					96	5021	gcuacaagaaauagaagua	(SEQ ID NO：11319)	M2-1
97	5082	gcacuucacaacuugauau	(SEQ ID NO：11320)	M2-1
					98	5104	ccuauauggagaugagcaa	(SEQ ID NO：11321)	M2-1
99	5160	ccaagagaaaaacugaaaa	(SEQ ID NO：11322)	M2-1
					100	5184	gcgaaauuaauaauugauu	(SEQ ID NO：11323)	M2-1
101	5185	cgaaauuaauaauugauuu	(SEQ ID NO：11324)	M2-1
					102	5254	gcacuaaucaagugcagua	(SEQ ID NO：11325)	M2-1
103	5318	ggacacacaaagaauuaaa	(SEQ ID NO：11326)	M2-2
					104	5359	gcaaaaucacacaccaaua	(SEQ ID NO：11327)	M2-2
105	5422	gcuuacuuaaguuaguaaa	(SEQ ID NO：11328)	M2-2
					106	5454	gggauaaaugacaaugaaa	(SEQ ID NO：11329)	SH
107	5455	ggauaaaugacaaugaaaa	(SEQ ID NO：11330)	SH
					108	5548	gguaaauugcuuauugcau	(SEQ ID NO：11331)	SH
109	5816	cgaaucaaugcacaaauau	(SEQID NO：11332)	SH
					110	7097	gggacaaauaacaauggau	(SEQ ID NO：11333)	L
111	7194	gcaauuggcucaugccuuu	(SEQ ID NO：11334)	L
					112	7352	gcagcaugaaauaaugaaa	(SEEID NO：11335)	L
113	7388	gcucacauuauuaaaacaa	(SEQ ID NO：11336)	L
					114	7436	ccuaaaauuaaguaugaua	(SEQ ID NO：11337)	L
115	7546	gguuuaguaacugguauaa	(SEQ IDNO：11338)	L
					116	7558	gguauaaucucaauaaauu	(SEQ ID NO：11339)	L
117	7669	gguguguaguaaaaagcaa	(SEQ ID NO：11340)	L
					118	7721	ccaacuguuaacauggaaa	(SEQ ID NO：11341)	L
119	7780	ggguaaguaacaaccugaa	(SEQ ID NO：11342)	L
					120	7812	ggacuaggauuuagaagua	(SEQ ID NO：11343)	L
121	7839	gguauguuaacuaauaaau	(SEQ ID NO：11344)	L
					122	8279	ggagagcuuaacagaacua	(SEQ ID NO：11345)	L
123	8304	gcauuuauacuaaaaauua	(SEQ ID NO：11346)	L
					124	8435	gcuaaguguacaagauuuu	(SEQ ID NO：11347)	L
125	8566	cgguauauccaaaaaauua	(SEQ ID NO：11348)	L
					126	8766	gggaaagaaagagaauuaa	(SEQ ID NO：11349)	L
127	8811	ccuggcaaacaaagacaaa	(SEQ ID NO：11350)	L
					128	8927	ggaaaugaaaucagaacuu	(SEQ ID NO：11351)	L
129	8962	ggaagaaugauaguuacaa	(SEQ ID NO：11352)	L
					130	8991	gcaagagccuccauaguaa	(SEQ ID NO：11353)	L

131	9014	ccuaaguaaauucaaucaa	(SEQ ID NO：11354)	L
					132	9133	ccacaaugauaugugcaua	(SEQ ID NO：11355)	L
133	9214	ggcuauacagauaccauau	(SEQ ID NO：11356)	L
					134	9483	ggugaaacauauauaucaa	(SEQ ID NO：11357)	L
135	9558	cccauaaaaaagauauuaa	(SEQ ID NO：11358)	L
					136	9577	ggguaggucccuggauaaa	(SEQ ID NO：11359)	L
137	9666	ggagaaaguauacuaguua	(SEQ ID NO：11360)	L
					138	9933	gcaaucagccauguggauu	(SEQ ID NO：11361)	L
139	10008	gccuuauuaucuauagaaa	(SEQ ID NO：11362)	L
					140	10009	ccuuauuaucuauagaaaa	(SEQ ID NO：11363)	L
141	10038	gcuacauuaacaacacuaa	(SEQ ID NO：11364)	L
					142	10092	gcuaagguaacaagugaua	(SEQ ID NO：11365)	L
143	10173	gcuauacacuauagcagaa	(SEQ ID NO：11366)	L
					144	10311	gguacaaagucuauaacua	(SEQ ID NO：11367)	L
145	10350	gcuaucaaugguugagaua	(SEQ ID NO：11368)	L
					146	10404	ggguuguuaucuaggauau	(SEQ ID NO：11369)	L
147	10581	gcgacuaguucucauuuaa	(SEQ ID NO：11370)	L
					148	10582	cgacuaguucucauuuaaa	(SEQ ID NO：11371)	L
149	10670	gguaggaucaagcacucaa	(SEQ ID NO：11372)	L
					150	10681	gcacucaagagaaaaaauu	(SEQ ID NO：11373)	L
151	10704	ccuguuuauaacagacaaa	(SEQ ID NO：11374)	L
					152	10795	ggcuaagaagauugcucaa	(SEQ ID NO：11375)	L
153	10796	gcuaagaagauugcucaau	(SEQ ID NO：11376)	L
					154	10822	gcauaggaaguuuagguau	(SEQ ID NO：11377)	L
155	10860	ccucuauuaccaagauuua	(SEQ ID NO：11378)	L
					156	10869	ccaagauuuaugaguguaa	(SEQ ID NO：11379)	L
157	10944	ccagcuuauaggacaacaa	(SEQ ID NO：11380)	L
					158	10947	gcuuauaggacaacaaauu	(SEQ ID NO：11381)	L
159	10954	ggacaacaaauuaccacuu	(SEQ ID NO：11382)	L
					160	11102	cccaaaacaauuagucuua	(SEQ ID NO：11383)	L
161	11154	ccuccuguauuucaaggaa	(SEQ ID NO：11384)	L
					162	11253	gggaagaugcuuaugccua	(SEQ ID NO：11385)	L
163	11364	gcaugccauugguguggaa	(SEQ ID NO：11386)	L
					164	11369	ccauugguguggaauauua	(SEQ ID NO：11387)	L
165	11666	ccuaucauuaguagguuau	(SEQ ID NO：11388)	L
					166	11679	gguuauauaggauuuaaaa	(SEQ ID NO：11389)	L
167	11688	ggauuuaaaaacugguuua	(SEQ ID NO：11390)	L
					168	11732	gcaugaaguacccuggauu	(SEQ ID NO：11391)	L
169	11764	gggagcuaguugaaauuaa	(SEQ ID NO：11392)	L
					170	11765	ggagcuaguugaaauuaaa	(SEQ ID NO：11393)	L
171	11874	cgauuaauuaggaagaaau	(SEQ ID NO：11394)	L
					172	12022	ccaguucagacuacaacaa	(SEQ ID NO：11395)	L
173	12042	gggaaguuaacaagaaauu	(SEQ ID NO：11396)	L
					174	12043	ggaaguuaacaagaaauua	(SEQ ID NO：11397)	L
175	12083	gcacguaaacagguauaau	(SEQ ID NO：11398)	L
					176	12151	ggaaauugauaaaggacuu	(SEQ ID NO：11399)	L
177	12164	ggacuuaaacccuaagguu	(SEQ ID NO：11400)	L
					178	12173	cccuaagguucuuuacuuu	(SEQ ID NO：11401)	L

179	12174	ccuaagguucuuuacuuua	(SEQ ID NO：11402)	L
					180	12204	gcagguaacuggauggcaa	(SEQ ID NO：11403)	L
181	12207	gguaacuggauggcaagaa	(SEQ ID NO：11404)	L
					182	12272	ggaugaucuugaucaccau	(SEQ ID NO：11405)	L
183	12367	ccacagaugcaacucaaaa	(SEQ ID NO：11406)	L
					184	12394	gggacuugauacacagaau	(SEQ ID NO：11407)	L
185	12395	ggacuugauacacagaaua	(SEQ ID NO：11408)	L
					186	12534	ggaacagaucuuuacuuau	(SEQ ID NO：11409)	L
187	12572	ggacugcaauauaaaguua	(SEQ ID NO：11410)	L
					188	12692	gccaugucacggagaaaua	(SEQ ID NO：11411)	L
189	12754	ccucaaaaaaacuagacaa	(SEQ ID NO：11412)	L
					190	12810	ggauuaagaauaccaauaa	(SEQ ID NO：11413)	L
191	12902	cggaaguaagauuauagaa	(SEQ ID NO：11414)	L
					192	12903	ggaaguaagauuauagaau	(SEQ ID NO：11415)	L
193	12961	gguuagagcauaucuugaa	(SEQ ID NO：11416)	L
					194	12990	ggugaauuaaacuaugauu	(SEQ ID NO：11417)	L
195	13035	cccaauaugaucaagcuua	(SEQ ID NO：11418)	L
					196	13036	ccaauaugaucaagcuuau	(SEQ ID NO：11419)	L
197	13061	ccugggaaaugcagagaua	(SEQ ID NO：11420)	L
					198	13064	gggaaaugcagagauaaaa	(SEQ ID NO：11421)	L
199	13065	ggaaaugcagagauaaaaa	(SEQ ID NO：11422)	L
					200	13071	gcagagauaaaaaaacuaa	(SEQ ID NO：11423)	L

下表37概述了双-萤光素酶检测结果。萤火虫萤光素酶作为内转染对照和萤光素酶检测对照(即，萤火虫萤光素酶转录子不是siRNA的靶)。花虫萤光素酶转录子与hMPV靶序列融合。花虫萤光素酶活性的减少表示细胞内花虫萤光素酶/hMPV靶序列转录子数目减少。因此，根据此检测，所测量花虫萤光素酶活性的较大减少是更有效siRNA的指征。siRNA效力表示为表37中的沉默百分比(％沉默)，计算为100×[1-(平均花虫siRNA/平均萤火虫siRNA)/(平均花虫sicontrol/平均萤火虫sicontrol)]。较高百分比与更有效siRNA相关联。

表37.200 siRNA对靶RNA降解效力的双-萤光素酶检测结果

hMPv靶基因	siRNA	萤火虫萤光素酶			花虫萤光素酶			％沉默
									N	Nsicontrol	27.928	30.5828	25.3713	47.7974	53.8565	42.2478	0％
N	1	30.5676	34.8861	31.0843	5.5751	5.8177	5.7094	90.520306
									N	2	34.6326	40.9162	41.3312	60.5914	66.5246	64.5825	12.235444
N	3	18.7181	26.9685	28.9728	39.1731	60.4988	68.5949	-20.602022
									N	4	27.9183	32.8811	32.7704	49.3759	57.7581	62.7936	2.8217953
N	5	30.0243	31.9289	37.605	52.6084	57.8041	65.4435	5.4806332
									N	6	18.712	21.1744	24.0004	11.6898	13.4643	13.1618	67.907131
N	7	39.1671	47.9692	46.2934	51.3052	65.0097	63.7821	27.773825
									N	8	30.3026	37.0956	33.5938	48.9493	64.1518	60.6797	7.9220868
N	9	35.0222	28.5869	32.3542	49.0298	39.227	44.5528	25.9432
									N	10	26.0519	23.1261	21.7516	36.0005	31.4406	28.4737	27.639966
N	11	23.5992	21.4999	24.566	36.6642	37.1155	43.3241	10.050993
									N	12	37.8536	31.3862	29.8096	51.8933	47.7502	43.2448	22.805658
N	13	27.2456	24.903	28.1906	39.0897	32.1443	39.7394	26.085092
									N	14	21.7298	20.521	18.591	25.9944	24.4481	21.3958	36.817815
N	15	33.9466	28.5711	32.9416	46.8615	42.5866	45.7029	24.239703
									N	16	40.9688	32.0063	34.3876	67.8157	55.4525	61.4958	7.9116736
N	17	20.4853	22.1031	21.0988	21.3855	21.3583	21.3474	46.149853
									N	18	20.3425	21.123	18.9807	19.5657	22.2023	18.1191	46.984248
N	19	24.3143	22.3699	21.9125	28.1652	25.1039	27.0592	37.337748
									N	20	29.8761	28.1125	28.8518	40.4098	38.2723	36.6134	28.955381
N	21	35.0731	36.1802	33.7572	61.344	62.583	58.5114	7.0339931
									N	22	18.0974	15.6114	18.4168	38.8525	31.0135	36.2891	-8.9758953
N	23	35.6841	34.8649	33.183	51.5648	50.7528	44.4457	24.291374
									N	24	35.767	33.8879	32.1497	61.7046	69.0208	55.6915	2.015241
N	25	25.2963	24.0016	22.5738	32.506	27.3097	26.8378	35.483791
									N	26	25.6974	26.4022	26.2649	34.9944	37.9287	35.6109	25.888246
N	27	26.0077	26.8305	29.8229	37.7121	38.4859	37.4114	26.454901
									N	28	23.4401	23.4625	20.671	15.6677	17.1257	14.6688	62.415268
N	29	24.4111	27.6527	21.3214	45.0223	46.2752	38.6559	5.241143
									N	30	24.1915	20.593	22.9204	47.4054	41.0789	45.5486	-5.9331685
N	31	35.4845	34.6695	32.716	41.0051	38.409	36.9601	39.464711
									N	32	25.3755	26.211	24.9847	9.9498	10.2209	9.3382	79.378122
N	33	23.0457	25.5582	27.6969	9.683	10.262	11.014	78.288067
									N	34	11.2645	11.9403	14.4547	11.8901	13.8073	13.65	44.090947
N	35	26.0071	29.8332	30.1544	38.4229	48.6692	47.6686	16.144371
									N	36	16.1825	18.755	18.5051	32.9247	36.1832	38.2632	-7.5079233
N	37	26.6079	26.5607	32.4129	46.0072	50.0075	57.9052	3.7600193
									N	38	24.1958	24.3966	25.632	46.9843	50.0746	47.8712	-4.4846628
N	39	20.0787	19.5131	19.2493	37.2365	36.7495	36.3744	-0.3628838
									N	40	26.8245	28.317	29.1997	38.0285	46.8881	45.6146	17.183818
N	41	23.9029	22.7504	18.1435	45.447	42.9659	39.0455	-4.2923884
									N	42	24.802	23.0239	22.5205	33.3397	27.5202	27.4041	32.859839
N	43	27.4113	26.1257	23.6277	53.1069	49.1756	46.2852	-3.0328251
									N	44	17.6333	17.4712	16.2981	30.8108	28.5366	26.7737	10.346937
N	45	23.3978	21.5174	21.7461	6.7082	6.407	67113	84.08477
									N	46	28.8204	24.9472	27.5777	45.2449	40.7861	42.2756	15.597137
N	47	16.6454	17.2237	14.8715	17.7277	18.8391	16.0972	42.181926
									N	48	19.0061	17.7011	16.3211	12.6826	11.95	11.394	63.645664
N	49	15.3041	13.7256	15.6344	27.2625	24.7802	26.1378	6.3343168
									N	50	29.6166	30.8804	29.1955	46.9922	48.8737	45.96	15.38642
N	51	26.862	26.8215	25.05	44.8789	42.9423	39.9379	13.169373
									N	52	18.6649	17.6678	14.733	34.3204	29.9523	27.0617	4.2925512
N	53	19.1458	17.9679	16.554	35.2927	34.2236	30.4593	0.3168657
									N	54	32.5823	33.059	32.3469	59.0335	58.463	53.5643	6.5848387

N	55	15.3767	14.9568	12.7516	19.6105	18.0042	17.0053	32.163218
									N	56	19.1216	19.1458	18.9002	25.5891	29.2977	24.5872	25.609794
N	57	23.8068	22.7135	20.3704	40.9168	35.7718	34.0778	11.389957
									N	58	11.4412	9.9783	11.0364	15.4384	15.2859	14.5539	25.348911
P	Psicontrol	11.2094	10.6081	9.4047	122.2887	131.1846	107.7269	0％
									P	59	10.697	13.8648	14.7481	7.2963	9.0423	9.3448	94.352372
P	60	11.878	12.6046	13.0613	4.9205	4.8981	5.2248	96.536445
									P	61	8.1227	7.0458	7.6793	84.1004	78.7462	77.9821	8.8872044
P	62	8.5033	9.2861	12.1278	110.8868	111.0465	136.1474	-3.4607181
									P	63	10.386	11.0685	11.9306	124.4945	132.1592	144.0445	-3.7481185
P	64	15.2151	19.144	15.4057	19.0666	25.0996	22.5453	88.412388
									P	65	10.2451	10.988	9.703	129.5517	132.5337	118.8359	-6.4351837
P	66	12.8992	17.8203	16.6212	90.4959	99.6181	121.6685	43.071128
									P	67	9.6135	9.9873	11.5392	105.3922	112.2033	120.7532	6.0792778
P	68	13.1206	12.5217	12.1532	137.4372	118.6314	116.0674	14.890682
									P	69	10.2777	8.8893	8.9836	126.6192	112.1464	111.3533	-7.5086526
M	Msicontrol	3.4037	3.3699	3.4842	20.6919	19.0309	20.8162	0％
									M	70	3.6233	4.5514	5.0324	10.2227	11.5743	8.4331	61.215941
M	71	3.3196	2.9542	4.016	18.8179	18.2287	21.247	4.0079913
									M	72	3.5326	4.1715	4.1092	19.1646	22.0002	20.3861	11.715531
M	73	2.2736	3.7619	2.8816	1.305	2.0649	1.4393	90.861596
									M	71	2.6656	3.0649	2.7177	23.7602	24.0959	21.4957	-39.096015
F	Fsicontrol	7.8571	6.7966	7.335	55.5336	49.8435	50.9222	0％
									P	75	8.8536	8.8282	6.4977	57.069	61.3785	50.0317	1.9739514
F	76	6.3894	5.9738	6.2884	49.3656	48.1072	52.2303	-12.916452
									F	77	8.4754	7.7906	7.6508	59.9011	61.6289	59.0789	-6.2376846
F	78	5.151	4.869	5.2859	14.5073	15.2357	15.3041	58.595219
									F	79	4.8134	4.503	4.6331	32.4704	38.5899	38.216	-10.207173
F	80	7.7561	8.3599	6.6592	5.0082	5.2792	4.1739	91.067199
									F	81	6.8885	8.1106	6.1432	9.4483	11.4738	8.2177	80.610043
F	82	5.6313	5.9351	4.3754	27.3103	26.5547	24.3652	30.963367
									F	83	8.5275	6.9636	7.4137	65.0738	56.1948	52.785	-6.9052485
F	84	6.8407	7.6623	7.2884	52.2169	58.999	54.3121	-6.8633676
									F	85	37.6262	42.2308	35.2346	9.3539	10.9493	9.3019	96.015867
F	86	21.7479	26.5692	26.0961	173.6864	202.6429	197.743	-19.488891
									F	87	33.2708	35.3616	33.2097	22.0311	25.3344	23.8915	89.162949
F	88	40.1018	41.192	35.8329	42.4389	47.5863	39.7739	82.835676
									F	89	27.6564	29.7642	26.5831	99.9944	105.5671	86.835	46.088095
F	90	22.8037	24.3579	19.5137	52.1498	56.7962	49.3069	63.238128
									F	91	24.6671	29.0884	24.0965	177.5542	192.488	169.1241	-7.2664445
F	92	22.5223	23.1552	21.8042	146.8529	152.6536	161.8563	-5.8930554
									M2-1	M2-1sicontrol	28.4749	31.2531	25.9436	110.5559	114.3964	98.9211	0％
M2-1	93	34.9502	33.0584	36.8185	57.1574	50.2616	59.1375	57.970946
									M2-1	94	40.4703	42.909	34.9406	112.9317	119.9721	101.7199	25.189854
M2-1	95	32.2247	23.4849	24.6175	34.8958	28.9595	26.8251	70.138409
									M2-1	96	20.668	23.1818	28.7744	93.0302	101.4748	115.0885	-12.764415
M2-1	97	20.6971	23.0886	22.3287	91.7718	107.8933	111.4815	-24.48889
									M2-1	98	31.7401	31.9422	26.3181	11.23	12.3105	10.841	89.894868
M2-1	99	36.5257	33.5963	34.508	24.6096	22.7964	24.4523	81.83303
									M2-1	100	27.784	30.3075	24.6241	109.3404	114.5398	97.2973	-2.7115507
M2-1	101	28.8863	27.6648	28.6818	116.8763	120.2008	123.0177	-11.756086
									M2-1	102	25.2279	34.3368	30.4127	27.9522	36.2849	28.8609	72.630396
M2-1	103	22.6833	26.793	28.4628	84.1138	93.7308	93.3007	7.9744776
									M2-1	104	33.2496	28.9952	28.0762	107.0015	96.3263	88.016	14.6754
M2-1	105	32.3711	26.2806	31.382	33.2508	28.4175	27.3049	73.85939

SH	SHsicontrol	ND	ND	ND	ND	ND	ND	ND
									SH	106	0.0333	0.0333	0.0339	0.0369	0.0357	0.0357	ND
SH	107	0.0284	0.0236	0.0248	0.0339	0.0303	0.0296	ND
									SH	108	0.0236	0.0224	0.0236	0.0309	0.0284	0.0254	ND
SH	109	0.0236	0.0218	0.0206	0.0351	0.0327	0.0333	ND
									L	Lsicontrol	15.3543	15.6713	13.5671	138.9425	116.8406	124.1569	0％
L	110	16.3441	18.0024	18.1615	164.1764	165.4551	170.5465	-11.799324
									L	111	14.7106	14.8183	13.9174	112.0454	104.3504	106.5387	12.761056
L	112	8.0489	7.7386	8.5729	60.4607	62.4535	62.3652	10.732891
									L	113	7.0749	6.171	5.2127	84.5844	72.9152	62.1946	-39.69105
L	114	3.9797	4.1261	5.1661	50.3263	55.8094	59.3057	-46.305228
									L	115	6.8081	7.2921	6.4898	97.8261	100.5111	79.4885	-58.367048
L	116	5.6126	6.0875	5.3155	57.1162	63.6412	54.0211	-20.556183
									L	117	3.7909	3.7849	3.6046	47.9384	47.1059	41.742	-43.593245
L	118	9.7205	10.2971	9.6933	9.5554	9.0218	7.0718	89.867809
									L	119	12.7631	12.5084	12.4219	109.7966	112.026	99.7978	-0.1444821
L	120	16.8837	18.9625	18.7411	102.0466	102.9952	111.7556	31.88563
									L	121	22.235	20.5791	19.7654	10.0878	10.7484	8.4385	94.509535
L	122	0.4846	0.4882	0.4725	2.6402	2.0437	2.0437	68.19647
									L	123	0.317	0.4102	0.32	3.2694	3.2422	3.529	34.490664
L	124	0.357	0.4386	0.2916	4.0674	4.2465	4.5296	19.286327
									L	125	0.4162	0.3908	0.3848	4.9047	4.3614	4.3372	22.014464
L	126	0.3128	0.2027	0.334	0.3896	0.2099	0.3436	92.414791
									L	127	0.2323	0.2396	0.2759	4.2072	3.4745	3.9349	-6.1369834
L	128	0.4937	0.3908	0.4834	5.5884	6.6175	7.6369	0.8890198
									L	129	0.4773	0.5372	0.4253	9.7847	9.7556	10.2118	-41.185021
L	130	0.3963	0.2547	0.2747	0.5052	0.5772	0.5221	88.157521
									L	131	0.3146	0.3086	0.3636	3.8333	4.1787	4.6518	12.31848
L	132	7.0682	5.7445	6.603	30.6342	26.784	28.5233	20.487506
									L	133	4.624	5.1213	4.2834	21.4594	26.3478	23.4686	8.733757
L	134	6.6114	5.0058	4.9973	22.5102	17.6533	19.1561	35.864802
									L	135	5.7675	5.4849	7.2552	24.2472	25.0531	32.0868	21.00657
L	136	6.3694	7.2261	8.4053	30.7001	32.8376	41.2804	14.417827
									L	137	6.8867	5.4559	5.1728	44.3592	35.7017	35.5135	-18.529674
L	138	6.4227	5.5279	6.0548	6.5794	4.8219	4.5926	84.04352
									L	139	5.6737	6.7881	7.6405	21.5126	17.7658	23.2332	44.140073
L	140	5.5122	6.1432	6.1958	28.1023	23.042	22.6173	25.775306
									L	141	3.6536	4.2471	3.5574	5.7336	4.1255	4.6186	77.302791
L	142	0.6219	0.6516	0.6032	3.6306	2.6088	2.7733	1.8973635
									L	143	1.3026	0.8857	1.0606	0.6141	0.3521	0.5009	90.775475
L	144	0.7472	0.6486	0.7768	4.7595	3.0801	3.2809	-4.5598996
									L	145	0.9783	0.7302	1.5458	1.0315	0.6564	1.1592	82.128305
L	146	0.6552	0.6903	0.9728	1.9433	1.6317	2.2821	48.390028
									L	147	0.5003	0.8071	0.8585	0.4568	0.7877	0.726	81.415167
L	148	0.7079	0.7314	0.8343	1.4514	1.0878	1.0745	67.531767
									L	149	0.631	0.6274	0.562	1.3092	0.9862	1.3364	59.245486
L	150	0.5257	0.5911	0.5197	0.1016	0.1047	0.0926	96.268955
									L	151	0.5161	0.8004	0.9638	0.1343	0.1174	0.1476	96.422926
L	152	0.9335	0.9142	0.9855	3.3438	3.7365	5.1679	11.688827
									L	153	1.0715	0.821	1.6577	4.4347	3.7934	6.263	16.618606
L	154	0.7242	0.7986	0.6026	2.4019	2.613	2.0286	32.30315
									L	155	0.925	0.6582	0.4719	3.1908	1.9088	1.8985	30.438682
L	156	0.7581	0.6474	0.6334	0.7478	0.7127	0.6207	79.148442
									L	157	0.4701	0.706	0.6002	0.0847	0.092	0.0768	97.084707
L	158	0.4447	0.7454	0.4937	0.6619	0.8071	0.4713	76.460404
									L	159	0.746	0.8355	0.8367	1.9596	1.8943	3.8629	34.812302
L	160	0.6588	0.9595	0.8077	2.6547	5.2484	4.0184	-19.850716

L	161	0.6486	0.9257	0.945	3.0117	4.7311	3.8781	-12.502042
									L	162	0.7647	0.4725	0.5378	3.0099	2.3456	2.7219	-10.987421
L	163	0.6177	0.4852	0.4187	0.4519	0.4072	0.3104	81.254361
									L	164	0.631	0.8119	0.7798	0.3618	0.4737	0.5911	84.346124
L	165	0.6467	0.4677	0.5506	3.4352	2.4412	2.2204	-18.604099
									L	166	0.8367	0.7702	0.8101	4.4691	2.9621	3.4485	-9.7844413
L	167	0.6213	0.6837	0.6238	3.9736	2.953	2.5664	-20.037463
									L	168	0.8591	0.5935	0.7423	1.069	0.8089	0.7157	71.180344
L	169	0.6171	0.677	0.608	1.3479	1.4883	1.2832	47.179666
									L	170	0.5512	0.6498	0.8361	2.2052	3.7734	3.8079	-17.16977
L	171	0.9293	0.8627	0.7266	3.0801	4.9658	2.8623	-5.6317365
									L	172	2.0032	1.792	1.5464	12.1696	15.1583	10.2687	-8.5798528
L	173	1.8713	1.8325	1.4593	11.9215	10.6305	10.0569	2.5688896
									L	174	1.9723	2.1544	1.7696	12.2555	15.0336	12.9966	-5.4006726
L	175	2.2845	2.2736	1.737	14.6313	13.14	11.1925	4.515963
									L	176	2.2379	1.766	2.682	14.0784	12.1278	15.7657	3.1564295
L	177	2.6209	2.2627	2.0733	14.86	13.82	12.2379	9.2660922
									L	178	1.8767	1.6843	1.5724	12.653	10.6928	10.3455	-1.2475919
L	179	1.9844	1.795	1.6287	12.6191	13.3905	11.0576	-5.7345954
									L	180	2.4478	2.3777	2.4146	11.9863	10.6982	9.5481	31.321182
L	181	1.5101	1.4405	1.9064	10.4411	11.2004	11.8973	-6.5249787
									L	182	2.247	1.9142	2.5821	9.8597	8.3871	9.5233	36.470271
L	183	1.9765	2.6795	2.3395	8.058	10.749	9.6431	37.261075
									L	184	2.5077	2.7921	2.9336	6.2999	6.2739	6.6713	63.941057
L	185	3.0413	1.9983	2.319	11.6989	7.6248	9.7835	38.979288
									L	186	2.0044	1.5869	2.1677	13.0329	10.4792	12.4007	3.8001869
L	187	2.1586	2.368	1.7188	13.1581	19.5391	14.2314	-15.9176
									L	188	2.7037	2.6523	2.8235	11.1042	11.538	12.1393	34.401548
L	189	2.0183	1.4992	2.1901	14.5236	12.1266	14.3954	-10.939223
									L	190	2.377	2.1502	2.077	13.1279	11.5004	12.6022	13.03376
L	191	2.8393	2.5688	2.4224	17.2576	15.5225	16.6073	2.7031659
									L	192	2.4872	1.8967	2.1217	14.4813	10.6032	11.3625	13.573591
L	193	2.1544	1.7672	1.6704	15.027	13.6294	11.1477	-9.8076724
									L	194	3.4201	2.5882	2.5253	23.5502	16.6369	15.3428	-0.3844975
L	195	2.8018	2.6305	2.247	18.415	17.2213	13.3796	15.5337526
									L	196	2.5337	2.2512	3.126	13.4286	15.7524	17.1917	9.5708334
L	197	2.898	3.8926	3.5477	6.9103	10.8767	6.9914	63.026023
									L	198	2.6227	2.2089	2.6789	8.8384	7.4633	7.8263	50.440774
L	199	2.0824	1.7696	2.0667	9.8337	9.8119	9.3515	24.42115
									L	200	2.2567	2.6426	2.5846	9.4743	11.6293	11.3843	33.032251

ND是无数据

对本实施例和表37所示数据，对靶花虫萤光素酶表现40％或更高沉默的siRNA被认为是有效siRNA。基于表37所示数据，以下57种siRNA认为是有效siRNA：1、6、17、18、28、32、33、34、45、47、48、59、60、64、66、70、73、78、80、81、85、87、88、89、90、93、95、98、99、102、105、118、121、122、126、130、138、139、141、143、145、146、147、148、149、150、151、156、157、158、163、164、168、169、184、197和198。在第二筛选进一步表征57种鉴别的有效siRNA，以确定57种中的哪些能有效诱导靶hMPV转录子直接降解。

筛选了57种siRNA(序列见下表38)诱导靶hMPV RNA降解的能力，该靶hMPV RNA转录自以下一种靶病毒基因：N基因、P基因、M基因、F基因、M2-1基因、M2-2基因或L基因。总之，以上公开了对本实施例用于转染siRNA和感染培养物中细胞的方法。

Dharmacon^TM的Sicontrol用作对照siRNA。以定量实时PCR来确定病毒RNA拷贝数，通过比较以siRNA转染的hMPV感染细胞分离的RNA的复制动力学与已知标准，该标准即以已知拷贝数的模板进行实时PCR所产生的复制动力学(Deffrasnes C，等，J Clin.Microbiol.43，488-90(2005))。从140μl感染细胞培养上清液提取病毒RNA，用作反转录酶和实时PCR的起始材料。较低病毒RNA拷贝数表示更有效的siRNA。而且，较大百分比的抑制表示更有效的siRNA。

表38.靶向人类偏肺病毒基因转录子的57种siRNA的核苷酸序列

siRNA在病毒靶序列中的5’核苷酸位置	siRNA核苷酸序列	SEQ ID	hMPV靶基因
				60	cuucaagggauucaccuaa	(SEQ ID NO：10885)	N
111	gagucucaauacacaauaa	(SEQ ID NO：10890)	N
				269	ggcucuaggaucagaaaga	(SEQ ID NO：10904)	N
280	cagaaagaguacaacagau	(SEQ ID NO：10905)	N
				435	gacaaagaggcaagaaaaa	(SEQ ID NO：10928)	N
506	gccuucagcaccagacaca	(SEQ ID NO：10938)	N
				513	gcaccagacacaccaauaa	(SEQ ID NO：10939)	N
514	caccagacacaccaauaau	(SEQ ID NO：10940)	N
				763	gaagcaaagcagaaaguuu	(SEQ ID NO：10959)	N
816	ggucaaacaaugcuaagggu	(SEQ ID NO：10966)	N
				846	gccagaucaucuaacaaca	(SEQ ID NO：10968)	N
1297	ggguaaugaagcagcaaaa	(SEQ ID NO：11282)	P
				1319	gcagaagcuuuccagaaau	(SEQ ID NO：11283)	P
1724	gcagaguccucaaucuuaa	(SEQ ID NO：11287)	P
				1898	gguauaagagaagaacuaa	(SEQ ID NO：11289)	P
2196	ggacacuuaucaaggcauu	(SEQ ID NO：11293)	M

2542	ccauaugggauggugucaa	(SEQ ID NO：11296)	M
				3449	ggcuugagagugaagugaa	(SEQ ID NO：11301)	F
3631	gcugucagcuucagucaau	(SEQ ID NO：11303)	F
				3697	gggauaacaccagcaauau	(SEQ ID NO：11304)	F
4010	ccacuguuuacuacccaaa	(SEQ ID NO：11308)	F
				4154	gcacaggaagacacccuau	(SEQ ID NO：11310)	F
4356	gggugaacagcauguaaua	(SEQ ID NO：11311)	F
				4522	ggaaacacuggcuucauua	(SEQ ID NO：11312)	F
4589	gcaucaucaucauaaucaa	(SEQ ID NO：11313)	F
				4716	cguaaagcuccaugcaaau	(SEQ ID NO：11316)	M2-1
4993	gcuauagucuacauaacau	(SEQ ID NO：11318)	N2-1
				5104	ccuauauggagaugagcaa	(SEQ ID NO：11321)	M2-1
5160	ccaagagaaaaacuggaaa	(SEQ ID NO：11322)	M2-1
				5254	gcacuaaucaagugcagua	(SEQ ID NO：11325)	M2-1
5422	gcuuacuuaaguuaguaaa	(SEQIDNO：11328)	M2-2
				7721	ccaacuguuaacauggaaa	(SEQ ID NO：11341)	L
7839	gguauguuaacuaauaaau	(SEQ ID NO：11344)	L
				8279	ggagagcuuaacagaacua	(SEQ ID NO：11345)	L
8766	gggaaagaaagagaauuaa	(SEQ ID NO：11349)	L
				8991	gcaagagccuccauaguaa	(SEQ ID NO：11353)	L
9933	gcaaucagccauguggauu	(SEQ ID NO：11361)	L
				10008	gccuuauuaucuauagaaa	(SEQ ID NO：11362)	L
10038	gcuacauuaacaacacuaa	(SEQ ID NO：11364)	L
				10173	gcuauacacuauagcagaa	(SEQ ID NO：11366)	L
10350	gcuaucaauggugaagaua	(SEQ ID NO：11368)	L
				10404	ggguuguuaucuaggauau	(SEQ ID NO：11369)	L
10581	gcgacuaguucucauuuaa	(SEQ ID NO：11370)	L
				10582	cgacuaguucucauuuaaa	(SEQ ID NO：11371)	L
10670	gguaggaucaagcacucaa	(SEQ ID NO：11372)	L
				10681	gcacucaagagaaaaaauu	(SEQ ID NO：11373)	L
10704	ccuguuuauaacagacaaa	(SEQ ID NO：11374)	L
				10869	ccaagauuuaugaguguaa	(SEQ ID NO：11379)	L
10944	ccagcuuauaggacaacaa	(SEQ ID NO：11380)	L
				10947	gcuuauaggacaacaaauu	(SEQ ID NO：11381)	L
11364	gcaugccauugguguggaa	(SEQ ID NO：11386)	L
				11369	ccauugguguggaauauua	(SEQ ID NO：11387)	L
11732	gcaugaaguacccuggauu	(SEQ ID NO：11391)	L
				11764	gggagcuaguugaaauuaa	(SEQ ID NO：11392)	L
12394	gggacuugauacacagaau	(SEQ ID NO：11407)	L
				13061	ccugggaaaugcagagaua	(SEQ ID NO：11420)	L
13064	gggaaaugcagagauaaaa	(SEQ ID NO：11421)	L

表98的数据概述了57种不同siRNA对转染了10nM siRNA的细胞中siRNA靶向hMPV转录子的病毒RNA拷贝数的单独效应。每个“PCR结果组”代表由实时PCR一起分析的57种siRNA子集的结果。从表39的数据，有10个“PCR结果组”。从三个单独PCR推导平均病毒RNA拷贝数。每个siRNA减少病毒RNA拷贝数的效力表示为抑制百分比(“％抑制”)。为了计算57种不同siRNA分别的抑制百分比(“％抑制”)，“PCR结果组”内每种siRNA的平均病毒RNA拷贝数除以同一“PCR结果组”sicontrol的平均病毒RNA拷贝数。该数字在表39中是标题为“siRNA∶sicontrol比”那一栏。将该数字乘以100而转化为百分比，然而用100％减去该结果而得到对每种siRNA的抑制百分比(指标题为“％抑制”的栏)。较高的抑制百分比表示该siRNA具有较高的减少靶hMPV转录子的病毒RNA拷贝数的能力，从而可能是病毒复制更有效的抑制剂。负的抑制百分比表示与对照siRNA相比病毒RNA拷贝数增加。

表39.57种不同siRNA对转染了10nM siRNA的细胞中hMPV靶向RNA的RNA拷贝数的效应

组1的PCR结果	siRNA#	三个不同PCR的病毒RNA拷贝数			平均病毒RNA拷贝数	SD	siRNA∶sicontrol比	％抑制
									1	2	3
		1	8.050E+03	ND								ND	8.050E+03	#DIV/0！	0.03	97％
	6				1.305E+05	ND	2.292E+03	6.640E+04	9.066E+04	0.22	78％
		17	6.010E+05	5.517E+05								5.862E+05	5.796E+05	2.530E+04	1.91	-91％
	18				3.894E+05	3.281E+05	4.095E+05	3.757E+05	4.240E+04	1.24	-24％
		28	3.314E+04	2.726E+05								4.852E+05	2.636E+05	2.262E+05	0.87	13％
	32				5.021E+04	2.589E+04	4.010E+04	3.873E+04	1.222E+04	0.13	87％
		icontrol	2.290E+05	2.482E+05								4.321E+05	3.031E+05	1.121E+05	1.00	0％
	无siRNA				ND	1.511E+05	7.041E+04	1.108E+05	5.706E+04	0.37	63％
组2的PCR结果	33				7.328E+03	2.186E+04	3.600E+04	2.173E+04	1.434E+04	0.15	85％
		34	1.170E+05	1.212E+05								7.694E+04	1.050E+05	2.443E+04	0.71	29％
	45				1.359E+04	4.752E+03	8.497E+03	8.946E+03	4.436E+03	0.06	94％
		47	3.141E+04	4.034E+04								5.323E+04	4.166E+04	1.097E+04	0.28	72％
	48				5.712E+04	9.462E+04	ND	7.587E+04	2.652E+04	0.51	49％
		59	8.746E+03	6.237E+03								2.844E+04	1.447E+04	1.216E+04	0.10	90％
	sicontrol				1.405E+05	1.570E+05	1.479E+05	1.485E+05	8.265E+03	1.00	0％
		无siRNA	1.952E+05	ND								1.814E+05	1.883E+05	9.758E+03	1.27	-27％

组3的PCR结果	60	2.941E+04	3.866E+04	3.815E+04	3.541E+04	5.200E+03	0.15	85％
									64	7.899E+05	4.453E+05	7.872E+05	6.741E+05	1.982E+05	2.86	-186％
	66	3.961E+05	4.259E+05	3.853E+05	4.024E+05	2.103E+04	1.71	-71％
									70	7.425E+04	4.081E+04	1.290E+05	8.135E+04	4.452E+04	0.35	65％
	73	1.96E+05	2.31E+05	2.018E+05	2.099E+05	1.849E+04	0.89	11％
									78	ND	5.741E+05	6.987E+04	3.220E+05	3.565E+05	1.37	-37％
	sicontrol	3.209E+05	1.070E+05	2.791E+05	2.357E+05	1.134E+05	1.00	0％
									无siRNA	1.032E+06	1.234E+06	1.153E+06	1.140E+06	1.017E+05	4.84	-384％
组4的PCR结果									80	1.952E+05	2.341E+05	1.820E+05	2.038E+05	2.700E+04	0.90	10％
	81	5.438E+05	2.847E+05	4.256E+05	4.180E+05	1.297E+05	1.85	-85％
									85	3.419E+05	1.860E+05	2.185E+05	2.488E+05	8.225E+04	1.10	-10％
	87	3.616E+05	3.363E+05	ND	3.490E+05	1.789E+04	1.54	-54％
									88	7.625E+05	4.093E+05	2.298E+04	3.983E+05	3.699E+05	1.76	-76％
	89	2.372E+05	2.484E+05	4.596E+05	3.151E+05	1.253E+05	1.39	-39％
									sicontrol	4.277E+05	1.088E+04	2.409E+05	2.265E+05	2.088E+05	1.00	0％
	无siRNA	2.213E+05	1.038E+06	8.192E+05	6.928E+05	4.228E+05	3.06	-206％
组5的PCR结果	90	7.341E+05	6.142E+05	5.923E+05	6.469E+05	7.634E+04	0.95	5％
									93	4.657E+05	2.050E+05	6.303E+05	4.337E+05	2.145E+05	0.64	36％
	95	8.222E+05	8.630E+05	8.650E+05	8.501E+05	2.415E+04	1.25	-25％
									98	3.501E+05	2.234E+05	3.626E+05	3.120E+05	7.701E+04	0.46	54％
	99	1.293E+06	6.597E+05	7.184E+05	8.904E+05	3.499E+05	1.31	-31％
									102	1.448E+06	9.564E+05	2.281E+06	1.562E+06	6.696E+05	2.30	-130％
	sicontrol	8.332E+05	6.529E+05	5.521E+05	6.794E+05	1.424E+05	1.00	0％
									无siRNA	8.604E+05	4.320E+05	7.782E+05	6.902E+05	2.274E+05	1.02	-2％
组6的PCR结果									105	1.861E+05	5.984E+05	5.187E+05	4.344E+05	2.187E+05	0.78	22％
	118	6.316E+04	8.239E+04	6.691E+04	7.082E+04	1.019E+04	0.13	87％
									121	4.263E+05	1.561E+06	7.021E+05	8.965E+05	5.918E+05	1.61	-51％
	122	4.748E+05	4.637E+05	7.151E+05	5.512E+05	1.421E+05	0.99	1％
									126	9.507E+04	6.768E+04	7.251E+04	7.842E+04	1.462E+04	0.14	86％
	130	7.206E+05	5.569E+05	1.267E+06	8.482E+05	3.718E+05	1.53	-53％
									sicontrol	4.939E+05	6.908E+05	4.835E+05	5.561E+05	1.168E+05	1.00	0％
	无siRNA	9.990E+05	7.928E+05	6.867E+05	8.262E+05	1.588E+05	1.49	-49％
组7的PCR结果	138	1.339E+05	1.687E+05	1.252E+05	1.426E+05	2.302E+04	0.89	11％
									139	8.793E+04	6.992E+04	1.275E+05	9.512E+04	2.946E+04	0.60	40％
	141	1.140E+05	1.016E+05	1.277E+05	1.144E+05	1.306E+04	0.72	28％
									143	6.155E+04	6.303E+04	6.659E+04	6.372E+04	2.591E+03	0.40	60％
	145	4.429E+04	2.153E+05	8.886E+04	1.162E+05	8.871E+04	0.73	27％
									146	1.625E+05	1.623E+05	1.954E+05	1.734E+05	1.905E+04	1.09	-9％
	sicontrol	2.484E+05	1280E+05	1.021E+05	1.595E+05	7.807E+04	1.00	0％
									无siRNA	1.071E+05	7.273E+04	1.292E+05	1.030E+05	2.846E+04	0.65	35％
组8的PCR结果									147	1.779E+05	1.606E+05	1.442E+05	1.609E+05	1.685E+04	0.62	38％
	148	1.630E+05	1.917E+05	1.733E+05	1.760E+05	1.454E+04	0.68	32％
									149	7.237E+04	7.417E+04	7.042E+04	7.232E+04	1.875E+03	0.28	72％

8	150	3.667E+04	6.480E+02	7.660E+04	3.797E+04	3.799E+04	0.15	85％
									151	4.377E+04	6.663E+04	5.460E+04	5.500E+04	1.144E+04	0.21	79％
	156	1.989E+05	2.3 19E+05	3.107E+05	2.472E+05	5.744E+04	0.96	4％
									sicontrol	1.922E+05	1.854E+05	3.950E+05	2.575E+05	1.191E+05	1.00	0％
	无siRNA	1.51 6E+05	2.667E+05	2.491E+05	2.225E+05	6.200E+04	0.86	14％
组9的PCR结果	157	1.251E+05	8.337E+04	1.102E+05	1.062E+05	2.115E+04	0.51	49％
									158	1.321E+05	1.709E+05	1.452E+05	1.494E+05	1.974E+04	0.72	28％
	163	3.724E+04	2.477E+04	3.181E+04	3.127E+04	6.252E+03	0.15	85％
									164	1.478E+04	1.923E+04	1.439E+04	1.613E+04	2.689E+03	0.08	92％
	168	6.360E+04	7.421E+04	4.968E+04	6.250E+04	1.230E+04	0.30	70％
									169	2.585E+05	2.151E+05	2.128E+05	2.288E+05	2.575E+04	1.10	-10％
	sicontrol	1.432E+05	3.689E+05	1.100E+05	2.074E+05	1.409E+05	1.00	0％
									无siRNA	1.438E+05	1.446E+05	3.690E+05	2.191E+05	1.298E+05	1.06	-6％
组10的PCR结果									184	1.978E+05	6.666E+04	6.764E+04	1.107E+05	7.543E+04	0.64	36％
	197	3.464E+04	8.338E+04	8.075E+04	6.626E+04	2.741E+04	0.38	62％
									198	9.685E+04	1.193E+05	1.606E+05	1.256E+05	3.234E+04	0.73	27％
	sicontrol	1.467E+05	1.857E+05	1.841E+05	1.722E+05	2.207E+04	1.00	0％
									无siRNA	7.338E+04	6.970E+04	6.507E+04	6.938E+04	4.164E+03	0.40	60％

ND是无数据；SD是标准偏差

表39的数据表示19种siRNA以10 nM浓度表现50％或更高抑制病毒基因转录子，其中6种siRNA靶向N转录子，2种siRNA靶向P转录子，1种siRNA靶向M转录子，1种siRNA靶向M2转录子，9种siRNA靶向L转录子。10组PCR结果组中无siRNA对照表现从-384％至63％的抑制百分比。sicontrol的病毒RNA拷贝数值作为每种PCR结果组的基线，并被标准化至0％抑制。以10nM浓度转染的57种siRNA表现从-186％至97％的抑制百分比，说明鉴别能够减少靶转录子RNA拷贝数的siRNA需要基于病毒靶转录子的“保守”区核苷酸序列的超过一个选择。以10nM浓度证明抑制百分比为50％或更高的siRNA认为是有效减少病毒RNA拷贝数的(显示60％和63％的两个无siRNA对照是溢出值，不考虑)。表现50％或更高抑制的siRNA包括siRNA 1、6、32、33、45、48、59、60、70、98、118、126、143、149、150、151、163、164、168和197。

表40的数据显示了57种不同siRNA对转染了100 nM siRNA(与此前数据系列表39相比10倍的siRNA)的细胞中siRNA靶向hMPV转录子的病毒RNA拷贝数的单独效应。每个PCR结果组代表由实时PCR一起分析的57种siRNA子集的结果。从表40的数据，有6个PCR结果组。每个siRNA减少病毒RNA拷贝数的效力表示为抑制百分比(“％抑制”)。从两个单独PCR推导平均病毒RNA拷贝数。为了计算57种不同siRNA分别的抑制百分比(％抑制)，PCR结果组内每种siRNA的平均病毒RNA拷贝数除以同一PCR结果组无siRNA的平均病毒RNA拷贝数。该数字在表40中是标题为“siRNA∶无siRNA比”那一栏。将该数字乘以100而转化为百分比，然而用100％减去该结果而得到对每种siRNA的抑制百分比(指标题为“％抑制”的栏)。较高的抑制百分比表示该siRNA具有较高的减少靶hMPV转录子的病毒RNA拷贝数的能力，从而可能是病毒复制更有效的抑制剂。负的抑制百分比表示与对照siRNA相比病毒RNA拷贝数增加。

表40.57种不同siRNA对转染了100nM siRNA的细胞中hMPV靶向RNA的RNA拷贝数的效应

组1的PCR结果	siRNA#	两个不同PCR的病毒RNA拷贝数		平均病毒RNA拷贝数	SD	siRNA∶无RNA比	％抑制
								1	2
		1	3.701E+04							1.134E+04	2.418E+04	1.82E+04	0.06	94％
	6			2.907E+05	1.600E+05	2.254E+05	9.24E+04	0.52	48％
		17	7.855E+05							5.195E+05	6.525E+05	1.88E+05	1.52	-52％
	18			3.411E+05	6.491E+05	4.951E+05	2.18E+05	1.15	-15％
		28	6.327E+05							8.135E+05	7.231E+05	1.28E+05	1.68	-68％
	32			2.343E+04	2.969E+04	2.656E+04	4.43E+03	0.06	94％
		33	1.647E+04							1.694E+04	1.671E+04	3.32E+02	0.04	96％
	34			3.274E+05	5.908E+05	4.591E+05	1.86E+05	1.07	-7％
		45	8.419E+03							1.862E+04	1.352E+04	7.21E+03	0.03	97％
	47			6.430E+04	1.277E+05	9.600E+04	4.48E+04	0.22	78％
		sicontrol	7.660E+05							ND	7.660E+05	ND	1.78	-78％
	无siRNA			4.303E+05	ND	4.303E+05	ND	1.00	0％
PCR	48			6.894E+04	9.162E+04	8.028E+04	1.60E+04	0.92	8％

组2的PCR结果	59	9.888E+03	1.083E+04	1.036E+04	6.66E+02	0.12	88％
								60	1.973E+04	7.538E+03	1.363E+04	8.62E+03	0.16	84％
	64	2.592E+05	2.777E+05	2.685E+05	1.31E+04	3.08	-208％
								66	1.529E+05	7.619E+04	1.145E+05	5.42E+04	1.31	-31％
	70	5.369E+04	5.627E+04	5.498E+04	1.82E+03	0.63	37％
								73	3.463E+04	8.408E+04	5.936E+04	3.50E+04	0.68	32％
	78	1.058E+05	2.303E+05	1.681E+05	8.80E+04	1.93	-93％
								80	5.007E+04	4.058E+04	4.533E+04	6.71E+03	0.52	48％
	81	6.689E+04	1.969E+05	1.319E+05	9.19E+04	1.51	-51％
								sicontrol	1.629E+05	ND	1.629E+05	ND	1.87	-87％
	无siRNA	8.716E+04	ND	8.716E+04	ND	1.00	0％
组3的PCR结果	85	2.370E+05	9.781E+05	6.076E+05	5.24E+05	2.07	-107％
								87	1.439E+05	1.298E+05	1.369E+05	9.97E+03	0.47	53％
	88	1.430E+05	2.324E+05	1.877E+05	6.32E+04	0.64	36％
								89	1.207E+05	1.024E+05	1.116E+05	1.29E+04	0.38	62％
	90	1.285E+05	2.080E+05	1.683E+05	5.62E+04	0.57	43％
								93	1.622E+05	1.628E+05	1.625E+05	4.24E+02	0.55	45％
	95	2.562E+05	2.235E+05	2.399E+05	2.31E+04	0.82	18％
								98	1.462E+05	8.387E+04	1.150E+05	4.41E+04	0.39	61％
	99	4.047E+05	3.334E+05	3.691E+05	5.04E+04	1.26	-26％
								sicontrol	1.983E+05	ND	1.983E+05	ND	0.68	32％
	无siRNA	2.331E+05	3.525E+05	2.928E+05	8.44E+04	1.00	0％
组4的PCR结果	102	3.121E+05	1.710E+05	2.416E+05	9.98E+04	0.47	53％
								105	2.041E+05	2.426E+05	2.234E+05	2.72E+04	0.44	56％
	118	8.322E+04	6.781E+04	7.552E+04	1.09E+04	0.15	85％
								121	2.18E+05	3.275E+05	2.732E+05	7.68E+04	0.53	47％
	122	2351E+05	2.788E+05	2.570E+05	3.09E+04	0.50	50％
								126	4.851E+04	6.012E+04	5.432E+04	8.21E+03	0.11	89％
	130	1.990E+05	2.836E+05	2.413E+05	5.98E+04	0.47	53％
								138	4.972E+05	5.052E+05	5.012E+05	5.66E+03	0.98	2％
	139	4.323E+05	5.880E+05	5.102E+05	1.10E+05	0.99	1％
								sicontrol	5.693E+05	ND	5.693E+05	ND	1.11	-11％
	无siRNA	3.044E+05	7.224E+05	5.134E+05	2.96E+05	1.00	0％
组5的PCR结果	141	3.845E+05	3.835E+05	3.840E+05	7.07E+02	1.14	-14％
								143	1.913E+05	2.214E+05	2.064E+05	2.13E+04	0.61	39％
	145	2.902E+05	1.968E+05	1.968E+05	6.60E+04	0.58	42％
								146	2.519E+05	5.554E+05	4.037E+05	2.15E+05	1.20	-20％
	147	3.821E+05	3.954E+05	3.888E+05	9.40E+03	1.15	-15％
								148	4.782E+05	ND	4.782E+05	ND	1.42	-42％
	149	1.933E+05	1.449E+05	1.691E+05	3.42E+04	0.50	50％
								150	1.969E+05	1.215E+05	1.592E+05	5.33E+04	0.47	53％
	151	1.267E+05	7.209E+04	9.940E+04	3.86E+04	0.29	71％
								156	4.391E+05	ND	4.391E+05	ND	1.30	-30％
	sicontrol	2.963E++05	ND	2.963E+05	ND	0.88	12％
								无siRNA	2.970E+05	3.773E+05	3.372E+05	5.68E+04	1.00	0％
组6的PCR结果								157	3.186E+05	1.685E+05	2.436E+05	1.06E+05	0.32	68％
	158	3.304E+05	3.789E+05	3.547E+05	3.43E+04	0.46	54％
								163	9.886E+04	1.176E+05	1.176E+05	1.33E+04	0.15	85％

	164	9.691E+04	1.317E+05	1.143E+05	2.46E+04	0.15	85％
								168	3.521E+05	2.240E+05	2.881E+05	9.06E+04	0.38	62％
	169	4.458E+05	9.643E+05	7.051E+05	3.67E+05	0.92	8％
								184	3.440E+05	1.789E+05	2.615E+05	1.17E+05	0.34	66％
	197	1.713E+05	1.475E+05	1.594E+05	1.68E+04	0.21	79％
								198	2.827E+05	4.828E+05	3.828E+05	1.41E+05	0.50	50％
	156	6.155E+05	ND	6.155E+05	ND	0.81	19％
								无siRNA	5.505E+05	9.779E+05	7.642E+05	3.02E+05	1.00	0％

ND是无数据；SD是标准偏差

表40的数据表示27种siRNA表现50％或更高抑制hMPV病毒基因体外表达，其中5种siRNA靶向N转录子，2种siRNA靶向P转录子，2种siRNA靶向F转录子，3种siRNA靶向M2转录子，15种siRNA靶向L转录子。总之，表43中所示的细胞转染/病毒感染的定量PCR结果与萤光素酶报告检测结果一致。5组PCR结果组中sicontrol对照表现从-87％至32％的抑制百分比。这与表42中sicontrol形成对比，在那里sicontrol作为计算抑制百分比的基线值。该数据组中，无siRNA对每种PCR结果组作为基线，被标准化至0％抑制。以100nM浓度转染的57种siRNA表现从-208％至97％的抑制百分比，说明鉴别能够减少靶病毒转录子RNA拷贝数的siRNA需要基于病毒靶转录子的“保守”区核苷酸序列的超过一个选择。基于sicontrol观察到的抑制百分比(即，32％抑制)，以100nM浓度证明抑制百分比为50％或更高的siRNA认为是有效减少病毒RNA拷贝数的。表现50％或更高抑制的siRNA包括siRNA1、32、33、45、47、59、60、87、89、98、102、105、118、122、126、130、149、150、151、157、158、163、164、168、184、197和198。

表39和40的数据证明在10nM或100nM浓度或两种浓度选择siRNA表现出有效减少靶hMPV转录子RNA拷贝数的能力。

实施例31：多病毒靶向

本实施例证明，能够介导hMPV靶RNA显著降解的siRNA也能降解RSV病毒RNA。使用此前所述的一般细胞培养和转染步骤。以定量实时PCR来确定病毒RNA拷贝数，通过比较以siRNA转染的RSV感染细胞分离的RNA的复制动力学与已知标准，该标准即以已知拷贝数的模板进行实时PCR所产生的复制动力学(Defeasnes C，等，J Clin.Microbiol.43，488-90(2005))。较低病毒RNA拷贝数表示更有效的siRNA。而且，较大百分比的抑制表示更有效的siRNA。

对表现出有效减少hMPV的L转录子的病毒拷贝数能力的siRNA 118、126、150、151和158评价了其对RSV靶RNA的相同能力。每种siRNA以10nM转染。数据显示于表41。

表41.6种不同siRNA对转染了10nM siRNA的细胞中RSV靶向转录子的RNA拷贝数的效应

siRNA#	三个不同PCR的病毒RNA拷贝数			平均病毒拷贝数	SD	siRNA∶sicontrol比	％抑制
								1	2	3
	118	1.852E+06	2.510E+06								2.055E+06	2.139E+06	3.368E+05	1.75	-75％
126				1.979E+06	1.222E+06	1.305E+06	1.502E+06	4.153E+05	1.23	-23％
	150	1.839E+06	2.164E+06								1.752E+06	1.918E+06	2.171E+05	1.57	-57％
151				1.073E+06	2.469E+06	9.120E+05	1.484E+06	8.561E+05	1.22	-22％
	158	1.367E+06	6.831E+05								9.153E+05	9.883E+05	3.475E+05	0.81	19％
sicontrol				1.258E+06	1.104E+06	1.299E+06	1.221E+06	1.029E+05	1.00	0％
	无siRNA	1.149E+06	1.741E+06								1.259E+06	1.383E+06	3.147E+05	1.13	-13％

表41的数据表示，siRNA158表现降解RSV转录子的能力，测量为约20％抑制RSV病毒拷贝数。这些数据表示可制备能够降解来自宽范围病毒家族的病毒转录子的多-病毒靶向siRNA。

尽管参考特定实施方案描述了本发明，本领域技术人员应理解对本发明可进行各种改变，可取代各等同物而不偏离本发明的主旨和范围。此外，对本发明的特定情形、材料、组合物、工艺、工艺步骤可进行许多改进以适合本发明的目标、主旨和范围。所有这些改进都包括在如下权利要求的范围内。

Claims (81)

1.一种诱导RNAi的实体，其靶向呼吸道病毒的转录子，其中所述诱导RNAi的实体长度在约15和约60个核苷酸之间，并包括：

a.第一核酸序列，其至少约84％相同于编码病毒蛋白的核酸的一部分；

b.第二核酸序列，其至少84％互补于所述第一核酸部分。

2.如权利要求1所述的诱导RNAi的实体，其中所述诱导RNAi的实体长度在约15和约40个核苷酸之间，并包括：

a.第一核酸序列，其至少约89％相同于编码病毒蛋白的核酸的一部分；

b.第二核酸序列，其至少89％互补于所述第一核酸部分。

3.如权利要求1所述的诱导RNAi的实体，其中所述诱导RNAi的实体长度在约15和约40个核苷酸之间，并包括：

a.第一核酸序列，其至少约94％相同于编码病毒蛋白的核酸的一部分；

b.第二核酸序列，其至少94％互补于所述第一核酸部分。

4.如权利要求1所述的诱导RNAi的实体，其中所述诱导RNAi的实体是siRNA或shRNA。

5.如权利要求1所述的诱导RNAi的实体，其中所述核酸包括3’突出端。

6.如权利要求5所述的诱导RNAi的实体，其中所述3’突出端包括脱氧胸苷。

7.如权利要求1所述的诱导RNAi的实体，其中所述病毒蛋白获自选自人类呼吸道合胞病毒、人类偏肺病毒、1型人类副流感病毒、2型人类副流感病毒、3型人类副流感病毒、4a型人类副流感病毒、4b型人类副流感病毒、鼻病毒和流感病毒的病毒。

8.如权利要求1所述的诱导RNAi的实体，其中所述病毒蛋白是呼吸道病毒蛋白。

9.如权利要求1所述的诱导RNAi的实体，其中所述病毒蛋白是流感病毒蛋白。

10.如权利要求1所述的诱导RNAi的实体，其中所述诱导RNAi的实体是shRNA，且进一步包括形成发夹环结构的第三核酸序列。

11.如权利要求10所述的诱导RNAi的实体，其中所述发夹环结构包括4至11个核苷酸。

12.一种分离的核酸序列，长约16至约35个核苷酸，沿其长度至少约85％相同于编码病毒蛋白的病毒核酸的一部分或其互补物。

13.如权利要求12所述的核酸，其中所述病毒蛋白获自选自人类呼吸道合胞病毒、人类偏肺病毒、1型人类副流感病毒、2型人类副流感病毒、3型人类副流感病毒、4a型人类副流感病毒、4b型人类副流感病毒、鼻病毒和流感病毒的病毒。

14.如权利要求12所述的核酸，其中所述病毒蛋白是呼吸道病毒蛋白。

15.如权利要求12所述的核酸，其中所述病毒蛋白是流感病毒蛋白。

16.一种诱导RNAi的实体，其靶向于流感病毒蛋白的转录子，其中所述诱导RNAi的实体长度在约15和约60个核苷酸之间，并包括：

a.第一核酸序列，其包括选自以下一组的核酸序列：SEQ ID NO1-10709、其互补物、或其长度有至少16个核苷酸或核苷酸序列至少80％同源于所述核酸序列的片段；以及

b.第二核酸序列，其至少80％互补于所述第一核酸序列。

17.如权利要求16所述的诱导RNAi的实体，其中所述第二核酸序列至少约90％互补于所述第一核酸部分。

18.如权利要求16所述的诱导RNAi的实体，其中所述诱导RNAi的实体是siRNA或shRNA。

19.如权利要求16所述的诱导RNAi的实体，其中所述诱导RNAi的实体是shRNA，并且进一步包括形成发夹环结构的第三核酸序列。

20.如权利要求19所述的诱导RNAi的实体，其中所述发夹环结构包括4至11个核苷酸。

21.一种靶向病毒蛋白转录子保守位点的siRNA，其中所述诱导RNAi的实体长度约15至约60个核苷酸。

22.如权利要求21所述的siRNA，其中所述保守位点长度约300核苷酸，并包括所述病毒蛋白基因的3’末端。

23.如权利要求21所述的siRNA，其中所述病毒蛋白获自选自人类呼吸道合胞病毒、人类偏肺病毒、1型人类副流感病毒、2型人类副流感病毒、3型人类副流感病毒、4a型人类副流感病毒、4b型人类副流感病毒、鼻病毒和流感病毒的病毒。

24.如权利要求21所述的siRNA，其中所述病毒蛋白是呼吸道病毒蛋白。

25.如权利要求21所述的siRNA，其中所述病毒蛋白是流感病毒蛋白。

26.一种siRNA，其减少编码第一病毒蛋白的第一基因和编码第二病毒蛋白的第二基因的表达。

27.如权利要求26所述的siRNA，其中所述第一病毒基因和所述第二病毒基因来自相同病毒的不同毒株。

28.如权利要求26所述的siRNA，其中所述第一病毒基因和所述第二病毒基因来自两种不同病毒。

29.如权利要求28所述的siRNA，其中一种病毒是流感病毒。

30.一种siRNA，其减少至少约25％的两种或多种编码病毒蛋白的基因的表达。

31.一种靶向转录子的RNAi诱导剂，所述转录子的序列包括编码病毒蛋白的核酸的靶部分。

32.如权利要求31所述的RNAi诱导剂，其中所述RNAi诱导剂是siRNA或shRNA。

33.如权利要求31所述的RNAi诱导剂，其中所述病毒蛋白获自选自人类呼吸道合胞病毒、人类偏肺病毒、1型人类副流感病毒、2型人类副流感病毒、3型人类副流感病毒、4a型人类副流感病毒、4b型人类副流感病毒、鼻病毒和流感病毒的病毒。

34.如权利要求31所述的RNAi诱导剂，其中所述病毒蛋白是呼吸道病毒蛋白。

35.如权利要求31所述的RNAi诱导剂，其中所述病毒蛋白是流感病毒蛋白。

36.一种组合物，其包括包括第一siRNA和第二siRNA，所述第一siRNA和第二siRNA各自减少编码病毒蛋白的基因的表达。

37.如权利要求36所述的组合物，其中所述第一siRNA减少编码第一病毒蛋白的第一基因的表达，且所述第二siRNA减少编码第二病毒蛋白的第二基因的表达。

38.如权利要求37所述的组合物，其中所述第一siRNA和第二siRNA减少所述第一基因和第二基因表达的至少约25％。

39.如权利要求37所述的组合物，其中所述第一基因和所述第二基因来自同一病毒种的两种毒株。

40.如权利要求37所述的组合物，其中所述第一基因和所述第二基因来自同一病毒属的两个种。

41.如权利要求37所述的组合物，其中所述第一基因和所述第二基因来自同一病毒科的两种病毒。

42.如权利要求36所述的组合物，其中所述组合物进一步包括第三siRNA，该第三siRNA减少编码第三病毒蛋白的第三基因表达至少约25％。

43.如权利要求42所述的组合物，其中所述组合物还包括阳离子聚合物。

44.一种诊断试剂盒，其包括针对至少部分的病毒蛋白基因检测所述基因的引物或探针，其中所述部分是保守位点。

45.一种减少靶病毒基因在病毒感染的哺乳动物细胞中表达的方法，其包括以下步骤：将所述细胞与减少病毒蛋白基因表达的siRNA接触，以使所述siRNA进入所述哺乳动物细胞的细胞质并减少所述病毒蛋白基因至少约25％的表达。

46.如权利要求45所述的方法，其中所述病毒蛋白获自选自人类呼吸道合胞病毒、人类偏肺病毒、1型人类副流感病毒、2型人类副流感病毒、3型人类副流感病毒、4a型人类副流感病毒、4b型人类副流感病毒、鼻病毒和流感病毒的病毒。

47.如权利要求45所述的方法，其中所述病毒蛋白基因是呼吸道病毒蛋白基因。

48.如权利要求45所述的方法，其中所述病毒蛋白基因是流感病毒蛋白基因。

49.一种递送siRNA至需要其的患者的方法，该方法包括将包含有效量的所述siRNA的组合物给药于所述患者，其中所述siRNA减少病毒蛋白基因至少约25％的表达。

50.如权利要求49所述的方法，其中所述siRNA以约0.1mg/kg患者体重至约20mg/kg患者体重的浓度递送给所述患者。

51.如权利要求49所述的方法，其中所述siRNA以约0.1mg/kg患者体重至约10mg/kg患者体重的浓度递送给所述患者。

52.如权利要求49所述的方法，其中所述siRNA以约0.1mg/kg患者体重至约50mg/kg患者体重的浓度递送给所述患者。

53.如权利要求49所述的方法，其中所述siRNA减少病毒蛋白基因至少约25％的表达。

54.如权利要求49所述的方法，其中所述siRNA包括选自SEQ ID NO1-10709的核酸序列。

55.如权利要求49所述的方法，其中所述组合物还包括阳离子聚合物。

56.如权利要求49所述的方法，其中所述组合物通过吸入、鼻内、口服或静脉内给药。

57.一种预防或治疗患者病毒感染的方法，其包括将包含靶向病毒蛋白基因的siRNA或shRNA的治疗化合物给药于所述患者。

58.如权利要求57所述的方法，其中所述siRNA或shRNA长度在约15和约60个核苷酸之间，并包括：

a.第一核酸序列，其至少约85％相同于编码病毒蛋白的核酸的一部分；

b.第二核酸序列，其至少85％互补于所述第一核酸部分。

59.如权利要求57所述的方法，其中所述siRNA是双链siRNA分子，其中所述siRNA分子的各链是约15至约50个核苷酸，并且其中所述siRNA分子的一条链包括与呼吸道病毒核酸序列内保守位点或其变体相同的核酸序列。

60.如权利要求57所述的方法，其中所述呼吸道病毒选自人类呼吸道合胞病毒、人类偏肺病毒、1型人类副流感病毒、2型人类副流感病毒、3型人类副流感病毒、4a型人类副流感病毒、4b型人类副流感病毒、鼻病毒和流感病毒。

61.如权利要求57所述的方法，其中所述核酸序列编码核蛋白基因。

62.如权利要求57所述的方法，其中所述呼吸道病毒是流感病毒，并且其中所述siRNA不是选自SEQ ID NO.10710-10751。

63.如权利要求57所述的方法，其中所述治疗化合物包括阳离子聚合物。

64.siRNA分子在制备抑制哺乳动物患者呼吸系统病毒繁殖的药剂中的用途，其包括向所述患者施用含有靶向病毒蛋白质基因的siRNA或shRNA的治疗化合物。

65.如权利要求64所述的siRNA分子的用途，其中所述siRNA或所述shRNA长度在约15和约60个核苷酸之间，并包括：

a.第一核酸序列，其至少约85％相同于编码病毒蛋白的核酸的一部分；

b.第二核酸序列，其至少85％互补于所述第一核酸部分。

66.如权利要求64所述的siRNA分子的用途，其中所述siRNA是双链siRNA分子，其中所述siRNA分子的各链是约15至约50个核苷酸，并且其中所述siRNA分子的一条链包括与呼吸道病毒核酸序列内保守位点或其变体相同的核酸序列。

67.如权利要求64所述的siRNA分子的用途，其中所述呼吸道病毒选自人类呼吸道合胞病毒、人类偏肺病毒、1型人类副流感病毒、2型人类副流感病毒、3型人类副流感病毒、4a型人类副流感病毒、4b型人类副流感病毒、鼻病毒和流感病毒。

68.如权利要求64所述的siRNA分子的用途，其中所述核酸序列编码蛋白(NP)基因。

69.如权利要求64所述的siRNA分子的用途，其中所述呼吸道病毒是流感病毒，并且其中所述siRNA不是选自SEQ ID NO.10710-10751。

70.如权利要求64所述的siRNA分子的用途，其中所述呼吸道病毒是流感病毒，并且其中所述siRNA选自SEQ ID NO.1-10709。

71.一种鉴定存在于两种或多种病毒的病毒蛋白转录子中的siRNA或shRNA靶序列的方法，该方法包括以下步骤：

a.提供编码来自病毒的病毒蛋白的核酸序列；

b.鉴定所述核酸序列的靶部分，其中所述部分包括约19个核苷酸且不包括多于3个连续鸟嘌呤核苷酸或多于3个连续胞嘧啶核苷酸；和

c.重复步骤(a)和(b)一次或多次，每次重复使用不同病毒，从而鉴定病毒蛋白转录子中的siRNA或shRNA靶序列。

72.如权利要求71所述的方法，其中所述核酸序列包括蛋白序列的保守位点。

73.如权利要求71所述的方法，该方法进一步包括产生结合于所述靶序列的siRNA或shRNA。

74.一种诊断病毒感染的方法，该方法包括如下步骤：测定患者是否感染了对权利要求1所述的诱导RNAi的实体抑制敏感的病毒。

75.如权利要求71所述的方法，该方法进一步包括将所述诱导RNAi的实体给药于所述患者的步骤。

76.一种治疗或预防流感病毒感染的方法，其包括将权利要求1所述的诱导RNAi的实体给药于需要其的患者。

77.一种抑制呼吸道病毒繁殖的双链siRNA分子，其中所述siRNA分子的各链是约15至约50个核苷酸，并且其中所述siRNA分子的一条链包括与呼吸道病毒核酸序列内保守位点或其变体相同的核酸序列。

78.如权利要求77所述的双链siRNA分子，其中所述呼吸道病毒选自人类呼吸道合胞病毒、人类偏肺病毒、1型人类副流感病毒、2型人类副流感病毒、3型人类副流感病毒、4a型人类副流感病毒、4b型人类副流感病毒、鼻病毒和流感病毒。

79.如权利要求78所述的双链siRNA分子，其中所述核酸序列编码蛋白(NP)基因。

80.如权利要求78所述的双链siRNA分子，其中所述呼吸道病毒是流感病毒，并且其中所述siRNA不是选自SEQ ID NO.10710-10751。

81.如权利要求78所述的双链siRNA分子，其中所述呼吸道病毒是流感病毒，并且其中所述siRNA选自SEQ ID NO.1-10709。

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