CN112156178A - Noro virus vaccine based on chimpanzee adenovirus vector, preparation method and application thereof - Google Patents

Noro virus vaccine based on chimpanzee adenovirus vector, preparation method and application thereof Download PDF

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CN112156178A
CN112156178A CN202011356032.7A CN202011356032A CN112156178A CN 112156178 A CN112156178 A CN 112156178A CN 202011356032 A CN202011356032 A CN 202011356032A CN 112156178 A CN112156178 A CN 112156178A
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史力
侯永凡
张超
张玲莉
刘海涛
李军瑞
王紫琰
朱钱钧
周晨亮
田文莉
刘革
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Immune Path Biotechnology Suzhou Co Ltd
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Abstract

The invention discloses a norovirus vaccine based on a chimpanzee adenovirus vector, a preparation method and application thereof. The norovirus vaccine is developed for the first time based on the chimpanzee adenovirus vector, and the vaccine can not be influenced by pre-stored adenovirus antibodies in human bodies; in the invention, the adenovirus vector vaccine is simple to prepare and good in safety, and does not need to add an adjuvant, and can adopt immune approaches such as muscle immunity or oral immunity and the like; the norovirus preventive vaccine is prepared on the basis of the replication-defective chimpanzee adenovirus vector, and a vaccine product which is simple to prepare, low in cost, good in safety, free of adjuvant and wide in application prospect is expected to be obtained.

Description

Noro virus vaccine based on chimpanzee adenovirus vector, preparation method and application thereof
Technical Field
The invention relates to the technical field of vaccines, in particular to a norovirus vaccine based on chimpanzee adenovirus vectors, a preparation method and application thereof.
Background
Norovirus (Norovirus), also known as Norwalk Viruses (Norwalk Viruses), is a highly contagious virus in the Human caliciviridae (Human Calicivirus) that is transmitted primarily through the fecal oral route and is also the primary pathogen causing intermittent outbreaks of nonbacterial gastroenteritis in the population. Norovirus is not clearly pathogenic in healthy people, but can cause severe disease and persist for extended periods of time in immunodeficient patients, the elderly and children. Norovirus infectious diarrhea is prevalent worldwide. In developed countries such as the united states, the netherlands, the uk, japan, australia, etc., 60-90% of annual outbreaks of nonbacterial diarrhea are caused by norovirus. In the children with diarrhea under 5 years old in China, the detection rate of the norovirus is about 15%, and the investigation of the serum antibody level also shows that the norovirus infection is very common in the Chinese population. At present, no vaccine and specific medicine aiming at norovirus exist.
Norovirus is a single-stranded positive-stranded RNA virus, with a genome size of about 7.5 kb, comprising a total of three Open Reading Frames (ORFs), of which ORF2 encodes the norovirus most major structural protein VP 1. Its icosahedral capsid structure is composed of 90 dimers of VP1 and a small amount of VP2, VP1 in turn contains two domains, S and P. Among them, the S domain is the base, and the P domain is the binding domain of the cellular receptor (HBGA), and is also the main target of neutralizing antibodies. Therefore, the development of norovirus preventive vaccines at present mainly takes the VP1 protein or P domain as a main antigen design site. Studies have shown that high titers of anti-gii.4 HBGA blocking antibody and specific IgA antibody levels as well as that immune memory B cells are associated with low risk pathogenicity of norovirus (Atmar r. l., Bernstein d. i., Lyon g. m., et al. (2015.) Serological Correlates of Protection against infection a gii.4 norovirus. Clin Vaccine immunol.22(8), 923-9.). Thus, B cell immunogenicity is the most important indicator for the evaluation of norovirus vaccines (Atmar R. L., Raman S., and Estes M.K. (2018); Human noviviruses: events advances in a 50-layer history. Current Opin infection Dis. 31 (5); 422) 432.).
Due to the lack of small animal models and virus in vitro cell culture systems, the development of norovirus vaccines is difficult, and no norovirus vaccine is currently on the market. The Norovirus Vaccine in Clinical stage mainly comprises a VLP Vaccine (Leroux-Roels G., Cramer J. P., Mendelman P., M., et al (2018) Safety and Immunogenicity of differentiation of Norovirus Vaccine repair in health additives: A Randomized, Controlled, Double-blank Clinical Trial. J. Infect Dis.217(4), 597-.
Norovirus has at least six gene groups and can be subdivided into at least 30 genotypes, which are common. GI.1 type, GII.3 type, GII.4 type, GII.17 type, etc. In the last decade, GII.4 is the most prevalent genotype of Norovirus, with 70-80% of outbreaks caused by GII.4 infection, and is prevalent mainly in vast low-Income regions of southeast Asia, south Asia, Africa, etc., with a tremendous economic burden (Mans J. (2019). Therefore, there is a need to develop a prophylactic vaccine against norovirus, of which gii.4 type vaccine is particularly important.
Disclosure of Invention
The technical problem to be solved by the present invention is to provide a norovirus vaccine based on chimpanzee adenovirus vectors, a preparation method and applications thereof, aiming at the defects in the prior art.
In order to solve the technical problems, the invention adopts the technical scheme that: the invention provides a norovirus vaccine, which is a norovirus recombinant adenovirus vaccine with immunogenicity obtained by inserting a nucleotide sequence of a norovirus target protein into a recombinant chimpanzee adenovirus vector plasmid to construct a recombinant plasmid, and then packaging and processing the recombinant plasmid.
In the invention, the replication-defective chimpanzee adenovirus vector vaccine can be constructed by modifying wild type chimpanzee adenovirus, and the invention has the following advantages: 1) after the adenovirus infects the cell, the genome can enter the cell nucleus, so the exogenous antigen carried by the adenovirus vector can stimulate the organism to generate stronger CD8+ T cell and antibody response through the endogenous protein processing way; 2) the modified replication-defective adenovirus has good safety; 3) the adenovirus genome is not integrated into the host genome, and has no hereditary carcinogenicity; 4) the adenovirus has infectivity on various cells, and is beneficial to the expression and presentation of antigen protein; 4) the adenovirus vector can be loaded with exogenous genes with the maximum length of 8 kb; 5) the timeliness of the adenovirus vector for expressing the foreign gene in vivo is longer; 6) the amplification and purification process of the adenovirus is mature, and virus particles with higher titer can be obtained; 7) the chimpanzee adenovirus has no influence on the pre-existing immunity of the vector in a human body, and is beneficial to the maximization of the immune effect of the vaccine.
In a preferred embodiment, the norovirus vaccine encodes the VP1 protein of norovirus.
In a preferred embodiment, the norovirus is one or more of gi.1 type, gii.3 type, gii.4 type, gii.17 type. The four norovirus viruses all encode the VP1 protein of norovirus.
In a further preferred embodiment, the norovirus is GII.4, the amino acid sequence of the norovirus GII.4 VP1 protein is SEQ ID NO. 1, the norovirus is derived from GeneBank (Accession number N95698.1), and the DNA sequence of the norovirus GII.4 VP1 protein is SEQ ID NO. 2.
In a preferred embodiment, the recombinant chimpanzee adenovirus vector is a replication-defective type 63 or replication-defective type 3 adenovirus.
The invention also provides a preparation method of the norovirus vaccine, which comprises the following steps:
1) inserting the nucleotide sequence of the norovirus target protein into a recombinant chimpanzee adenovirus vector plasmid to construct a recombinant plasmid;
2) after enzyme digestion linearization, the recombinant plasmid is transfected into adenovirus packaging cells, and then the cells are cultured until about 80% of the cells have obvious cytopathic effect;
3) collecting cells, breaking the cells by adopting a repeated freeze thawing mode, and centrifugally collecting supernate;
4) infecting adenovirus packaging cells with the supernatant, and culturing until most cells change from adherent to suspension state;
5) performing repeated amplification culture to a certain volume according to the steps 3) and 4), collecting cells, crushing, and centrifuging supernatant;
6) and (3) purifying the recombinant adenovirus by taking the supernatant to obtain purified virus liquid, wherein the virus liquid is norovirus recombinant adenovirus vaccine stock solution.
In a preferred embodiment, the packaging cell is an adherent cell line or a suspension cell line that can support replication-defective adenovirus propagation.
In a preferred embodiment, the adenovirus packaging cell is an adherent HEK293 cell line.
In a preferred embodiment, the adenovirus purification protocol is cesium chloride density gradient centrifugation.
In a preferred embodiment, the recombinant chimpanzee adenovirus vector plasmid is constructed by modifying the wild type chimpanzee adenovirus 63 or type 3 genome sequence by deletion and/or replacement of the E1, E3 and E4 regions, and then inserting the modified sequence into a transfer vector plasmid.
In a preferred embodiment, the wild type chimpanzee adenovirus type 63 is selected, the DNA sequence of the obtained recombinant chimpanzee adenovirus vector plasmid is SEQ ID NO. 3, and the modified replication-defective chimpanzee adenovirus type 63 genome sequence contained in the recombinant chimpanzee adenovirus vector plasmid is SEQ ID NO. 4.
In a preferred example, the recombinant plasmid is an open reading frame of norovirus GII.4 VP1 gene inserted between delta E1 (E1 modification region) sites MluI and EcoRI in a recombinant chimpanzee adenovirus type 63 genome sequence contained in a vector plasmid, the open reading frame is an expression frame sequence of norovirus GII.4 VP1 initiated by a CMV promoter, and the DNA sequence of the open reading frame is shown as SEQ ID NO: 5.
In a preferred embodiment, the recombinant plasmid is constructed by the following method: after the open reading frame sequence of the norovirus GII.4 type VP1 gene is completely designed in sequence analysis software, a recombinant adenovirus vector plasmid pChAD63-GII.4 capable of expressing the norovirus GII.4 type VP1 protein is obtained in a gene synthesis mode, and the nucleotide sequence of the recombinant adenovirus vector plasmid is shown as SEQ ID NO. 6.
In a preferred embodiment, the norovirus recombinant adenovirus obtained after the recombinant plasmid is linearized by digestion and transfected into an adenovirus packaging cell is recombinant chimpanzee adenovirus type 63 virus ChAd63-gii.4 comprising the antigen sequence of norovirus type gii.4 VP1, the complete genome sequence of which is SEQ ID No. 7.
In a preferred embodiment, the norovirus is one or more of type GI.1, type GII.3, type GII.4, type GII.17, a recombinant chimpanzee adenovirus type 63 virus obtained at one time, such as ChAd63-GI.1, ChAd63-GII.3, ChAd63-GII.17 or ChAd63-GII.4 as described above; the recombinant chimpanzee adenovirus type 63 virus obtained by fusing multiple norovirus can be named as ChAd63-GI.1-GII.3, ChAd63-GI.1-GII.4, ChAd63-GI.1-GII.3-GII.4-GII.17, etc.
The sequences contained in the present invention are as follows:
SEQ ID NO: 1: norovirus gii.4 type VP1 protein amino acid sequence;
SEQ ID NO: 2: a DNA sequence optimized by norovirus GII.4 type VP1 protein codon;
SEQ ID NO: 3: recombinant chimpanzee adenovirus type 63 empty vector plasmid pChAD63 sequence;
SEQ ID NO: 4: recombinant chimpanzee adenovirus type 63 empty carrier virus ChAd63 sequence;
SEQ ID NO: 5: delta E1 deletes the sequence of the foreign gene coding expression reading frame containing norovirus GII.4 type VP1 inserted between the region points MluI and EcoRI;
SEQ ID NO: 6: a recombinant adenovirus vector plasmid pChAD63-GII.4 sequence containing norovirus GII.4 type VP1 protein;
SEQ ID NO: 7: recombinant adenovirus genome ChAd63-gii.4 sequences comprising norovirus gii.4 type VP1 protein.
The invention also provides the application of the norovirus vaccine as described above in preparing a medicament or a kit for preventing or treating norovirus related diseases.
The invention has the beneficial effects that:
1. the norovirus vaccine is developed for the first time based on the chimpanzee adenovirus vector, and because the chimpanzee adenovirus is not popular in people, the vaccine of the invention is not influenced by the pre-stored adenovirus antibody in human body;
2. the adenovirus vector vaccine is simple to prepare and good in safety, does not need to add an adjuvant, can adopt immune approaches such as muscle immunity or oral immunity and the like, and has good market competitiveness.
3. The novel norovirus preventive vaccine not only has originality, but also has better immunogenicity and feasibility, and can be used for treating single muscleThe injection can induce high-level specific antibody response and CD8 in mice+T cell responses.
4. The norovirus preventive vaccine is prepared on the basis of the replication-defective chimpanzee adenovirus vector, and a vaccine product which is simple to prepare, low in cost, good in safety, free of adjuvant and wide in application prospect is expected to be obtained.
Drawings
FIG. 1 is a schematic map of the recombinant adenovirus vector plasmid pChAD 63-GII.4; A. replication-defective recombinant vector plasmid pChAD63 sequence map, and B. adenovirus recombinant plasmid pChAD63-GII.4 sequence map carrying norovirus GII.4 type VP1 gene.
FIG. 2 restriction enzyme digestion identification results of recombinant adenovirus vector plasmid pChAD63-GII.4 and recombinant adenovirus ChAd 63-GII.4; A. the restriction enzyme identification map of pChAD63-GII.4 plasmid, the restriction enzyme identification map of recombinant adenovirus ChAd63-GII.4 genome, the typical cytopathic phenomenon after HEK293 cells are infected by the recombinant adenovirus ChAd63-GII.4, the schematic diagram of adenovirus purification by a cesium chloride density gradient ultracentrifugation method, and the expression result of target protein VP1 after HEK293 cells are infected by the recombinant adenovirus ChAd63-GII.4 is identified by Western-blot.
FIG. 3 levels of antibody and B cell responses following immunization of mice with the recombinant adenovirus vector ChAd63-GII.4 vaccine; A. dynamic change of VP 1-specific IgG antibody titer in serum was measured by ELISA after single intramuscular injection of different doses of the recombinant adenovirus vector vaccine in BALB/c mice (n = 5) (FIG. A also shows auxiliary reference numerals 1-6 for 6 curves), and B-E.BALB/c mice were injected with 5X 10 single intramuscular injection10 Separating serum and spleen lymphocytes after blood is taken, and detecting the light absorption value (B) of each subtype antibody in the serum and the titer (C) of the IgG antibody by ELISA; detecting the number (D) of B cells which can secrete IgG and IgA and are specific to VP1 in splenic lymphocytes and the number (E) of memory B cells by using ELISPOT; the ChAd63-EGFP and ChAd63-EGFP-mCherry viruses are respectively used as negative controls, the antibody titer is shown as geometric mean titer and standard deviation, and the rest results are mean value and standard deviation; a, p<0.05；**，p<0.01；***，p<0.001；****，p<0.0001; ASC: antibody secreting cells (antibody secreting cells).
FIG. 4T cell immune response results after recombinant adenovirus vector ChAd63-GII.4 vaccine immunization of mice; BALB/c mice (n = 5) single intramuscular injection of 5 × 1010 After 4 weeks, splenic lymphocytes are separated from the VPs recombinant adenovirus, a VP1 polypeptide library (VP 1 Peptide Pool) is added for stimulation, and antigen-specific T cell immunoreaction is detected through ELISPOT and ICS tests; ChAd63-EGFP-mCherry virus as a negative control, results are shown as mean and standard deviation; a, p<0.05；****，p<0.0001; SFU: spot forming unit (spot forming unit).
Detailed Description
The present invention is further described in detail below with reference to examples so that those skilled in the art can practice the invention with reference to the description.
It will be understood that terms such as "having," "including," and "comprising," as used herein, do not preclude the presence or addition of one or more other elements or groups thereof.
Through a series of intensive researches, a novel norovirus preventive vaccine is constructed based on replication-defective chimpanzee adenovirus bodies for the first time. The vaccine can induce high-level and durable antibody and T cell immune response in mice.
In a preferred embodiment, the replication-defective chimpanzee adenovirus vector is engineered from a wild-type viral genomic sequence. In a further example, the delta E1 position of a type 63 vector is exemplifiedMluI andEcoRthe open reading frame sequence of norovirus GII.4 type VP1 protein is inserted between I (FIG. 1). After the sequence is constructed in sequence analysis software, a professional gene synthesis company is entrusted to carry out gene sequence synthesis, and finally the chimpanzee adenovirus recombinant plasmid pChAD63-GII.4 which covers accurate sequence information and has a sufficient amount of purified transfection level and can express an exogenous gene is obtained.
The present invention also provides a method for preparing a norovirus vaccine, the method comprising: the recombinant chimpanzee adenovirus vector plasmid of norovirus is packaged and processed to obtain the adenovirus vector norovirus vaccine with immunogenicity. Specifically, the method comprises the following steps:
1) inserting the nucleotide sequence of the norovirus target protein into a recombinant chimpanzee adenovirus vector plasmid to construct a recombinant plasmid;
2) after enzyme digestion linearization, the recombinant plasmid is transfected into adenovirus packaging cells, and then the cells are cultured until about 80% of the cells have obvious cytopathic effect;
3) collecting cells, breaking the cells by adopting a repeated freeze thawing mode, and centrifugally collecting supernate;
4) infecting adenovirus packaging cells with the supernatant, and culturing until most cells change from adherent to suspension state;
5) performing repeated amplification culture to a certain volume according to the steps 3) and 4), collecting cells, crushing, and centrifuging supernatant;
6) and (3) purifying the recombinant adenovirus by taking the supernatant to obtain purified virus liquid, wherein the virus liquid is norovirus recombinant adenovirus vaccine stock solution. The harvested virus can be used for immunization of mice after purification. The determination of the virus titer is carried out according to methods customary in the art.
The present invention also provides a method of systematically assessing the immunogenicity of a chimpanzee adenovirus vector norovirus vaccine in mice, the method comprising: the purified virus is used for immunizing BALB/c mice according to a certain dose, blood is collected from eye sockets of the mice after immunization, serum is separated, lymphocytes are separated from spleens, and the level of antibody and T cell response induced by the vaccine is detected by adopting immunological methods such as ELISA, FluoroSpot, ICS and the like.
The invention is further illustrated below with reference to specific embodiments. It should be understood that the embodiments of the present invention are illustrative only and are not intended to limit the scope of the present invention. The experimental procedures, the conditions of which are not specified in the following examples, are generally carried out according to the conditions recommended by the manufacturers of the conventional experimental conditions or the relevant reagents (kits).
Example 1
1. Experimental Material
1.1 cells
The HEK293 cell line was purchased from ATCC cell bank (cat # CRL-1573) in the United states, and the medium was DMEM (GIBCO, # 11995-040) containing 10% fetal bovine serum (GIBCO, # 10091-148).
1.2 BALB/c mice
The mice involved in the experiment were purchased from Shanghai Spiro-bikai laboratory animals Co. All animal experiments were performed in the Shanghai laboratory animal resources center SPF barrier.
2. Experimental methods
2.1 packaging of recombinant chimpanzee adenovirus ChAd63-GII.4
Plasmid pChAD63-GII.4 was synthesized by Kinzhi Biotech, Suzhou. Using restriction endonucleasesSwaI plasmid pChAD63-GII.4 was linearized. After 6-well plates were plated with HEK293 cells and the cell density reached 80% -90%, approximately 6. mu.g of linearized pChAD63-GII.4 digest was transfected with the transfection reagent Lipofectamine 2000 (Invitrogen, # 11668019), the cytopathic effect was observed daily and the negative control was uninfected cells. After about 4-6 days, successful virus packaging can be demonstrated if significant cytopathic effect is observed compared to the negative control (FIG. 2C). And harvesting transfected cells, repeatedly freezing and thawing for three times, centrifuging and taking supernatant, and taking the supernatant as initial virus stock solution of the recombinant chimpanzee adenovirus ChAd 63-GII.4.
2.2 amplification of recombinant chimpanzee adenovirus ChAd63-GII.4
When HEK293 cells were cultured in DMEM medium containing 10% fetal bovine serum to a cell density of approximately 100%, the initial virus stock was added to the cell culture medium and the cells were cultured. When the cells have cytopathic effect and almost all the cells are changed from adherent to floating state, the cells can be collected by centrifugation. Resuspending the cells with a suitable amount of DMEM, repeatedly freezing and thawing for three times to lyse the cells, and centrifuging to obtain the supernatant. The supernatant can be further repeatedly amplified according to the above method to achieve a certain concentration of virus in the virus supernatant collection liquid.
2.3 purification and titre determination of recombinant chimpanzee adenovirus ChAd63-GII.4
Amplifying the viral antigenThe solution was purified by cesium chloride density gradient centrifugation as described in literature (Zhou et al, 2010) (fig. 2D), followed by addition of glycerol to a concentration of 10% and long-term storage in a refrigerator at-80 ℃. Mu.l of the test virus was dispensed and A in solution was measured using a NanoPhotometer (IMPLEN, # N60)260Values, and the purified virus titer was roughly calculated according to the following formula: titer = A260 × 1.1 × 1012 vps/ml。
2.4 identification of recombinant adenovirus vector plasmid pChAD63-GII.4 and recombinant adenovirus ChAd63-GII.4 sequences
And (3) plasmid sequence identification: taking 500 ng of gene synthetic plasmid to perform restriction enzyme digestion identification, comprisingPvuIHF (NEB, # R3150L) single cleavage,XbaI(NEB, # R0145S) Single enzyme cleavage,BamHIHF (NEB, # R3136S) single cleavage. And (3) identifying the sequence of the viral genome: taking 0.5-1 × 1012 vps purified virus, kit DNeasy Blood&The virus genome was extracted with Tissue Kit (QIAGEN, # 69504), and the extracted virus genome was digested with the same digestion system. And verifying the correctness of the sequence by comparing the actual enzyme cutting map with the predicted enzyme cutting map of the software of the expected sequence. The results showed that both the obtained plasmid sequence and the obtained viral genome sequence completely met the expected results (fig. 2A, B).
2.5 Western-blot detection of GII.4 VP1 protein expression
Taking different doses (10)3、5 ×103And 104 vps/cell) of chimpanzee adenovirus ChAd63-gii.4 infected HEK293 cells. After 24 hs, centrifuging at low temperature of 1,000 rpm for 5 mins, and discarding the supernatant; cracking cells on ice by using a protein lysate containing a protease inhibitor, and centrifuging to obtain a supernatant; mixing appropriate amount of protein supernatant with the sample buffer solution, and boiling for 10 mins; after centrifugation, SDS-PAGE electrophoresis is carried out; transferring the protein on the gel to a PVDF membrane after electrophoresis; after the membrane is transferred, sealing the membrane by 5% of skim milk for 2 hs; after washing the membranes 3 times with PBST, 1:200 dilution of Norovirus GII.4 antibody (Abcam, # ab 80024) was added and incubated for 1 h; after washing the membrane with PBST, 1:2500 dilution of Goat Anti-mouse IgG (H + L) -HRP Conjugate was added and incubated for 1H; after washing the membrane with PBST, DAB (B)Tiangen, # PA 110) was developed in the dark. The results show that the target protein VP1 can be normally expressed after HEK293 cells are infected by virus, and typical reticulocyte lesions which are typical of ChAd63 type adenovirus infection are formed (FIG. 2E).
2.6 immunization of mice
Taking purified recombinant adenovirus stored at-80 ℃, diluting the recombinant adenovirus with a proper amount of PBS, and injecting 50 mul of the recombinant adenovirus into left and right hind leg muscles of a mouse; and (3) after immunization, performing orbital blood collection on the mouse, standing at 37 ℃ for 1 h or overnight at 4 ℃, centrifuging at 6,000 rpm for 15 mins, and taking supernatant, and inactivating at 56 ℃ for 30 mins to obtain the serum to be detected.
2.7 ELISA detection of antibody levels in mouse serum
ELISA plates (Corning, # 9018) were coated with 1 μ g/ml norovirus GII.4 type VP1 protein (Shanghai Zezun Biotech Co., Ltd, #65spR671 (2.4) 180808P) (100 μ l/well) overnight at 4 ℃; after washing the plate 5 times with PBST on day 2, blocking the plate for 1 h at 37 ℃ with 5% skimmed milk (200 μ l/well); after PBST washing, adding 100 mul of diluted mouse serum according to a multiple ratio, and incubating for 1 h at 37 ℃; after PBST washing, adding 1:10000 diluted Goat Anti-mouse IgG (H + L) -HRP Conjugate into 100 mul/hole, and incubating for 1H at 37 ℃; after PBST plate washing, developing solution (substrate buffer solution 9 ml; TMB 1 ml; 3% H) was added to 100 μ l/well2O2) Developing at 37 deg.C in dark for 10 mins; and adding 50 mul of 2M sulfuric acid solution into each well to terminate the reaction, and reading the plate under the condition of 450 nm/620 nm double-wavelength. The results show that a single intramuscular injection of the recombinant chimpanzee adenovirus vector norovirus gii.4 type vaccine induces a high level and a long lasting antibody immune response in mice compared to the negative control ChAd63-EGFP virus (fig. 3A, C).
2.8 detection of antibody subtypes by ELISA
Coating the ELISA plate with 1 mug/ml norovirus GII.4 VP1 protein (100 mul/well) overnight at 4 ℃; after washing the plate 5 times with PBST on day 2, blocking the plate for 1 h at 37 ℃ with 5% skimmed milk (200 μ l/well); after PBST washing, adding 100 mul of mouse serum diluted at 1:2000, and incubating at room temperature for 2 hs; after PBST washing, 100. mu.l of Mouse monoclonal antibody isotyping reagents (Sigma, # ISO 2) diluted at 1:1000 was added and incubated for 30 mins at room temperature; PBST WashAfter the plate, adding 100 mul 1:5000 diluted Goat Anti-mouse IgG (H + L) -HRP Conjugate, and incubating for 15 mins at room temperature; after PBST plate washing, 100. mu.l of color development solution (9 ml of substrate buffer solution; TMB 1 ml; 3% H) was added to each well2O2) Developing at 37 deg.C in dark for 10 mins; and adding 50 mul of 2M sulfuric acid solution into each well to terminate the reaction, and reading the plate under the condition of 450 nm/620 nm double-wavelength. The results show that the recombinant chimpanzee adenovirus vector norovirus type gii.4 vaccine can induce antibody responses of various subtypes, with the highest level of IgG2a subtype, compared to the negative control ChAd63-EGFP-mCherry virus (fig. 3B).
2.9 ELISPOT detection of Antibody Secreting Cells (ASC)
Pre-wetting a 96-well PVDF plate by using 15 mul of 35% ethanol solution for no more than 1 min, and then washing the plate by using 200 mul/well PBS for 5 times according to the instruction of a kit (Mouse IgG ELISPOT Basic: MabTech, Code #3825-2A and Mouse IgA ELISPOT Basic: MabTech, Code # 3865-2H); coating overnight at 4 ℃ with 100 μ l/well GII.4 VP1 protein (1 μ g/ml); washing with PBS for 5 times, and sealing with 200 mul/well complete culture medium at normal temperature for at least 30 mins; add 200 μ l of freshly isolated mouse splenic lymphocytes per well (5X 10)5Cells/well), incubation at 37 ℃ for about 48 hrs followed by subsequent steps to color count according to kit instructions. Part of the cells, according to the kit instructions, in 24-well plates (2.8X 10)6Cells/well) was pre-loaded with R848 and IL-2 for about 48 hrs; collecting cells after stimulation is finished, and detecting secretory IgG by using ELISPOT&IgA memory B lymphocytes. The results show that the recombinant chimpanzee adenovirus vector norovirus gii.4 type vaccine can induce specific IgG ASC response significantly, but IgA B cells or memory IgG, IgA B cells have no significant change (fig. 3D, E).
2.10 mouse IFN-. gamma./IL-5 FluoroSpot detection of T cell response
Mouse lymphocyte isolation: dissecting spleen, grinding in 6-well plate containing 2 ml RPMI 1640 culture medium (Gibco, # 72400047) and copper mesh, filtering cell suspension with copper mesh to 15 ml centrifuge tube, adding 3 ml RPMI 1640 solution, centrifuging at 4 deg.C for 6 min at 250 g, and discarding supernatant; adding 3 ml of erythrocyte lysate (Solarbio, Cat # R1010) into each tube, carrying out centrifugation at 250 g and 6 min at 4 ℃ after resuspension, and discarding the supernatant; adding 5 ml RPMI 1640 into each tube, resuspending, centrifuging at 250 g and 5 min at 4 ℃, and discarding the supernatant; 1 ml of RPMI 1640-10% FBS-1% P/S (complete medium) was added for resuspension, and the cells were counted by dilution 40X for use.
A total of 7 polypeptides were tested by Nanjing Kinsley for the synthesis of norovirus GII.4 VP1 protein, which contained 4 MHC Class II restriction polypeptides and 3 Class I restriction polypeptides (Table 1). The polypeptides were dissolved as specified after synthesis, and the concentration of each polypeptide was 10 mg/ml after dissolution, and the final concentration of each polypeptide was 5. mu.g/ml at the time of use.
TABLE 1 detection of synthetic VP1 antigen
Figure 552914DEST_PATH_IMAGE002
Note: polypeptide information was retrieved from database IEDB: http:// www.iedb.org/.
A96-well PVDF plate was pre-wetted with 15. mu.l/well 35% ethanol for not more than 1 min according to the kit (MabTech, # FS-4143-2) instructions, and then washed 5 times with 200. mu.l/well PBS; dilution of the coating antibody (anti-IFN-. gamma.mAb) with PBS&anti-IL-5 mAb) to 15. mu.g/ml, 100. mu.l/well diluted antibody was added and coated overnight at 4 ℃; washing with 200 μ l/well PBS for 5 times, adding 200 μ l/well complete culture medium, and sealing at room temperature for at least 30 mins; the blocking solution was discarded and 190. mu.l of cell suspension (3X 10) was added5Cells/well) and 10 μ l polypeptide stimulating solution; the negative control well is 10 mul of polypeptide diluent, and the positive control well is 5 mug/ml Con A; then adding 1:1000 diluted anti-CD28 antibody; 37 ℃ and 5% CO2Incubation for 2 days, followed by secondary antibody incubation, development and plate reading according to kit instructions. The results show that the recombinant chimpanzee adenovirus vector norovirus GII.4 type vaccine can stimulate the body to generate stronger IFN-gamma + T cell reaction, and is mainly CD8+T cell responses. MHC Class II restricted epitope polypeptides stimulated a lower IFN-. gamma.response but higher than the control group (FIG. 4A).
2.11 intracellular cytokine staining for detection of T cell responses
Spleen lymphocytes were isolated at 1X 10 per well6The cells were plated in 96-well cell culture plates with 5. mu.g/ml polypeptide and 1:1000 dilution of BFA protein transport inhibitor (BD, # 555029) at 37 ℃ with 5% CO2Culturing for 6 hrs; after harvesting the cells and washing with PBS, the cells were stained with Aqua (Life Technologies, # L34965), and anti-CD3 (Biolegend, # 10024), anti-CD4 (BD, # 553047) fluorescently labeled antibodies for 30 mins at 4 ℃ respectively; fixing the rupture membrane for about 20 mins according to the kit instruction; staining with anti-IFN-gamma (BD, # 554413), anti-IL-2 (BD, # 560538), anti-TNF-alpha (BD, # 554419) for 30 mins at 4 ℃; finally, the cells were washed with pre-cooled PBS and resuspended and tested on a BD FACSCAnto II machine. The results show that norovirus GII.4 type vaccine induces CD4+T cells can secrete a small amount of IFN-gamma, but do not secrete IL-2 and TNF-alpha; in contrast, norovirus GII.4-type vaccine induced CD8 production+T cells can secrete a variety of cytokines such as IFN-gamma, IL-2 and TNF-alpha. In conclusion, the recombinant chimpanzee adenovirus vector norovirus GII.4 type vaccine mainly induces antigen-specific CD8+T cell responses (figure 4B, C).
Conclusion
Currently, the most common development strategy for norovirus vaccines is to construct norovirus VLP vaccines, which induce higher levels of immune response in the body after multiple immunizations due to the similarity of VLPs to native viruses. In the embodiment, a novel norovirus vaccine is successfully constructed by using a chimpanzee adenovirus type 63 vector, a single immunization strategy is adopted to immunize a mouse, the specific antibody of the mouse against GII.4 and the T cell response level are detected at different time points after immunization, and the result shows that the single immunization of ChAd63-GII.4 can induce and generate stronger and lasting specific immune response.
While embodiments of the invention have been disclosed above, it is not limited to the applications listed in the description and the embodiments, which are fully applicable in all kinds of fields of application of the invention, and further modifications may readily be effected by those skilled in the art, so that the invention is not limited to the specific details without departing from the general concept defined by the claims and the scope of equivalents.
Sequence listing
<110> Yidao biological (Suzhou) science and technology Co., Ltd
<120> norovirus vaccine based on chimpanzee adenovirus vector, preparation method and application thereof
<160> 7
<170> SIPOSequenceListing 1.0
<210> 1
<211> 540
<212> PRT
<213> Artificial sequence (Artificial sequence)
<400> 1
Met Lys Met Ala Ser Ser Asp Ala Asn Pro Ser Asp Gly Ser Thr Ala
1 5 10 15
Asn Leu Val Pro Glu Val Asn Asn Glu Val Met Ala Leu Glu Pro Val
20 25 30
Val Gly Ala Ala Ile Ala Ala Pro Val Ala Gly Gln Gln Asn Val Ile
35 40 45
Asp Pro Trp Ile Arg Asn Asn Phe Val Gln Ala Pro Gly Gly Glu Phe
50 55 60
Thr Val Ser Pro Arg Asn Ala Pro Gly Glu Ile Leu Trp Ser Ala Pro
65 70 75 80
Leu Gly Pro Asp Leu Asn Pro Tyr Leu Ser His Leu Ala Arg Met Tyr
85 90 95
Asn Gly Tyr Ala Gly Gly Phe Glu Val Gln Val Ile Leu Ala Gly Asn
100 105 110
Ala Phe Thr Ala Gly Lys Ile Ile Phe Ala Ala Val Pro Pro Asn Phe
115 120 125
Pro Thr Glu Gly Leu Ser Pro Ser Gln Val Thr Met Phe Pro His Ile
130 135 140
Ile Val Asp Val Arg Gln Leu Glu Pro Val Leu Ile Pro Leu Pro Asp
145 150 155 160
Val Arg Asn Asn Phe Tyr His Tyr Asn Gln Ser Asn Asp Pro Thr Ile
165 170 175
Lys Leu Ile Ala Met Leu Tyr Thr Pro Leu Arg Ala Asn Asn Ala Gly
180 185 190
Asp Asp Val Phe Thr Val Ser Cys Arg Val Leu Thr Arg Pro Ser Pro
195 200 205
Asp Phe Asp Phe Ile Phe Leu Val Pro Pro Thr Val Glu Ser Arg Thr
210 215 220
Lys Pro Phe Thr Val Pro Ile Leu Thr Val Glu Glu Met Thr Asn Ser
225 230 235 240
Arg Phe Pro Ile Pro Leu Glu Lys Leu Phe Thr Gly Pro Ser Gly Ala
245 250 255
Phe Val Val Gln Pro Gln Asn Gly Arg Cys Thr Thr Asp Gly Val Leu
260 265 270
Leu Gly Thr Thr Gln Leu Ser Pro Val Asn Ile Cys Thr Phe Arg Gly
275 280 285
Asp Val Thr His Ile Ala Gly Thr Gln Glu Tyr Thr Met Asn Leu Ala
290 295 300
Ser Gln Asn Trp Asn Asn Tyr Asp Pro Thr Glu Glu Ile Pro Ala Pro
305 310 315 320
Leu Gly Thr Pro Asp Phe Val Gly Lys Ile Gln Gly Val Leu Thr Gln
325 330 335
Thr Thr Arg Gly Asp Gly Ser Thr Arg Gly His Lys Ala Thr Val Ser
340 345 350
Thr Gly Ser Val His Phe Thr Pro Lys Leu Gly Ser Val Gln Phe Ser
355 360 365
Thr Asp Thr Ser Asn Asp Phe Glu Thr Gly Gln Asn Thr Lys Phe Thr
370 375 380
Pro Val Gly Val Val Gln Asp Gly Ser Thr Thr His Gln Asn Glu Pro
385 390 395 400
Gln Gln Trp Val Leu Pro Asp Tyr Ser Gly Arg Asp Ser His Asn Val
405 410 415
His Leu Ala Pro Ala Val Ala Pro Thr Phe Pro Gly Glu Gln Leu Leu
420 425 430
Phe Phe Arg Ser Thr Met Pro Gly Cys Ser Gly Tyr Pro Asn Met Asn
435 440 445
Leu Asp Cys Leu Leu Pro Gln Glu Trp Val Gln His Phe Tyr Gln Glu
450 455 460
Ala Ala Pro Ala Gln Ser Asp Val Ala Leu Leu Arg Phe Val Asn Pro
465 470 475 480
Asp Thr Gly Arg Val Leu Phe Glu Cys Lys Leu His Lys Ser Gly Tyr
485 490 495
Val Thr Val Ala His Thr Gly Gln His Asp Leu Val Ile Pro Pro Asn
500 505 510
Gly Tyr Phe Arg Phe Asp Ser Trp Val Asn Gln Phe Tyr Thr Leu Ala
515 520 525
Pro Met Gly Asn Gly Thr Gly Arg Arg Arg Ala Leu
530 535 540
<210> 2
<211> 1623
<212> DNA
<213> Artificial sequence (Artificial sequence)
<400> 2
atgaagatgg ccagctccga tgccaatccc tccgatggct ccacagccaa tttagtgccc 60
gaagtgaata acgaggtcat ggccttagag cccgtggtgg gagctgctat cgctgctccc 120
gttgctggac agcagaacgt gattgaccct tggattagga ataacttcgt gcaagccccc 180
ggtggcgagt ttaccgtcag ccctcgtaac gcccccggtg agattctgtg gagcgctccc 240
ctcggccccg atctgaatcc ctatttaagc catctggcca gaatgtacaa cggatacgct 300
ggaggcttcg aggtccaagt tattctggcc ggcaacgcct tcaccgccgg caagatcatc 360
ttcgccgccg tgccccccaa ctttcctacc gagggcctca gcccttccca agttaccatg 420
ttccctcaca tcatcgtgga cgtgagacag ctggagcccg ttctgatccc tttacccgat 480
gttcgtaaca acttctacca ttacaaccag agcaacgacc ccaccatcaa actgatcgct 540
atgctgtata cacctttaag agccaacaat gccggcgacg acgtgttcac cgtgagctgt 600
agagtgctca ctcgtcccag ccccgatttt gacttcattt ttttagtccc ccccaccgtg 660
gaatctcgta ccaaaccctt caccgtgcct attctcaccg tggaggagat gaccaattct 720
cgtttcccta tccctttaga gaaactgttt accggcccct ccggcgcttt cgtggtgcaa 780
cctcagaacg gtcgttgtac cacagacggc gtgctgctgg gcacaaccca gctgtccccc 840
gtgaacatct gtacctttcg tggagacgtg acccacatcg ctggcaccca agaatatacc 900
atgaatttag ccagccagaa ctggaacaac tatgacccca ccgaagagat ccccgctcct 960
ctgggaaccc ccgacttcgt cggaaagatt caaggtgtgc tgacacagac caccagaggc 1020
gatggaagca ctcgtggaca taaggctaca gtcagcaccg gcagcgtgca ctttacaccc 1080
aaactgggca gcgtgcaatt cagcacagac accagcaacg acttcgagac tggtcagaat 1140
accaagttca cccccgtggg cgtggtgcaa gatggaagca ccacccacca gaacgagccc 1200
cagcagtggg ttttacccga ttactccggt cgtgactccc ataacgtcca cctcgccccc 1260
gctgtggctc ccacattccc cggtgagcag ctgctctttt tcagaagcac catgcccgga 1320
tgcagcggct accccaacat gaatctcgac tgtttactgc ctcaagaatg ggtgcagcac 1380
ttctaccaag aagctgcccc cgctcagtcc gatgtcgctt tattacgttt cgtgaacccc 1440
gataccggaa gggttttatt tgagtgcaag ctgcataaga gcggatatgt gacagtggct 1500
cacaccggcc agcacgattt agtgatcccc cccaatggct actttcgttt cgactcttgg 1560
gtgaatcagt tctacacact ggcccccatg ggcaacggaa ccggaagaag aagagctctc 1620
tga 1623
<210> 3
<211> 31593
<212> DNA
<213> Artificial sequence (Artificial sequence)
<400> 3
atttaaatgg cgcgccgggc ccgggccgca tagttaagcc agccccgaca cccgccaaca 60
cccgctgacg cgccctgacg ggcttgtctg ctcccggcat ccgcttacag acaagctgtg 120
accgtctccg ggagctgcat gtgtcagagg ttttcaccgt catcaccgaa acgcgcgaga 180
cgaaagggcc tcgtgatacg cctattttta taggttaatg tcatgataat aatggtttct 240
tagacgtcag gtggcacttt tcggggaaat gtgcgcggaa cccctatttg tttatttttc 300
taaatacatt caaatatgta tccgctcatg agacaataac cctgataaat gcttcaataa 360
tattgaaaaa ggaagagtat gagtattcaa catttccgtg tcgcccttat tccctttttt 420
gcggcatttt gccttcctgt ttttgctcac ccagaaacgc tggtgaaagt aaaagatgct 480
gaagatcagt tgggtgcacg agtgggttac atcgaactgg atctcaacag cggtaagatc 540
cttgagagtt ttcgccccga agaacgtttt ccaatgatga gcacttttaa agttctgcta 600
tgtggcgcgg tattatcccg tattgacgcc gggcaagagc aactcggtcg ccgcatacac 660
tattctcaga atgacttggt tgagtactca ccagtcacag aaaagcatct tacggatggc 720
atgacagtaa gagaattatg cagtgctgcc ataaccatga gtgataacac tgcggccaac 780
ttacttctga caacgatcgg aggaccgaag gagctaaccg cttttttgca caacatgggg 840
gatcatgtaa ctcgccttga tcgttgggaa ccggagctga atgaagccat accaaacgac 900
gagcgtgaca ccacgatgcc tgtagcaatg gcaacaacgt tgcgcaaact attaactggc 960
gaactactta ctctagcttc ccggcaacaa ttaatagact ggatggaggc ggataaagtt 1020
gcaggaccac ttctgcgctc ggcccttccg gctggctggt ttattgctga taaatctgga 1080
gccggtgagc gtgggtctcg cggtatcatt gcagcactgg ggccagatgg taagccctcc 1140
cgtatcgtag ttatctacac gacggggagt caggcaacta tggatgaacg aaatagacag 1200
atcgctgaga taggtgcctc actgattaag cattggtaac tgtcagacca agtttactca 1260
tatatacttt agattgattt aaaacttcat ttttaattta aaaggatcta ggtgaagatc 1320
ctttttgata atctcatgac caaaatccct taacgtgagt tttcgttcca ctgagcgtca 1380
gaccccgtag aaaagatcaa aggatcttct tgagatcctt tttttctgcg cgtaatctgc 1440
tgcttgcaaa caaaaaaacc accgctacca gcggtggttt gtttgccgga tcaagagcta 1500
ccaactcttt ttccgaaggt aactggcttc agcagagcgc agataccaaa tactgttctt 1560
ctagtgtagc cgtagttagg ccaccacttc aagaactctg tagcaccgcc tacatacctc 1620
gctctgctaa tcctgttacc agtggctgct gccagtggcg ataagtcgtg tcttaccggg 1680
ttggactcaa gacgatagtt accggataag gcgcagcggt cgggctgaac ggggggttcg 1740
tgcacacagc ccagcttgga gcgaacgacc tacaccgaac tgagatacct acagcgtgag 1800
ctttgagata gcgccacgct tcccgaaggg agaaaggcgg acaggtatcc ggtaagcggc 1860
agggtcggaa caggagagcg cacgagggag cttccagggg gaaacgcctg gtatctttat 1920
agtcctgtcg ggtttcgcca cctctgactt gagcgtcgat ttttgtgatg ctcgtcaggg 1980
gggcggagcc tatggaaaaa cgccagcaac gcggcctttt tacggttcct ggccttttgc 2040
tggccttttg ctcacatgtt ctttcctgcg ttatcccctg attctgtgga taaccgtatt 2100
accgcctttg agtgagctga taccgctcgc cgcagccgaa cgaccgagcg cagcgagtca 2160
gtgagcgagg aagcggaaga gcgcccaata cgcaaaccgc ctctccccgc gcgttggccg 2220
attcattaat gcagctggca cgacaggttt cccgactgga tttaaatcat catcaataat 2280
atacctcaaa cttttggtgc gcgttaatat gcaaatgagg tgtttgaatt tggggatgcg 2340
gggcgctgat tggctgagag acgggcgacc gttaggggcg gggcgggtga cgttttgatg 2400
acgtggccgt gaggcggagc cggtttgcaa gttctcgtgg gaaaagtgac gtcaaacgag 2460
gtgtggtttg aacacggaaa tactcaattt tcccgcgctc tctgacagga aatgaggtgt 2520
ttctgggcgg atgcaagtga aaacgggcca ttttcgcgcg aaaactgaat gaggaagtga 2580
aaatctgagt aattccgcgt ttatggcagg gaggagtatt tgccgagggc cgagtagact 2640
ttgaccgatt acgtgggggt ttcgattacc gtatttttca cctaaatttc cgcgtacggt 2700
gtcaaagtcc ggtgttttta cgtaggcgtc agctgatcgc cagggtattt aaacctgcgc 2760
tctctagtca agaggccact cttgagtgcc agcgagtaga gttttctcct ccgcgccgcg 2820
agtcagatct acactttgaa aggcgatcgc cgatatcatt tccccgaaaa gtgccacctg 2880
accgtaacta taacggtcct aaggtagcga aagctcagat ctcccgatcc cctatggtgc 2940
actctcagta caatctgctc tgatgccgca tagttaagcc agtatctgct ccctgcttgt 3000
gtgttggagg tcgctgagta gtgcgcgagc aaaatttaag ctacaacaag gcaaggcttg 3060
accgacaatt gcatgaagaa tctgcttagg gttaggcgtt ttgcgctgct tcgcgatgta 3120
cgggccagat atacgcgttg aattcatcta tgtcgggtgc ggagaaagag gtaatgaaat 3180
ggcattatgg gtattatggg tctgcattaa tgaatcggcc agatatcgac atatgctggc 3240
caccgtacat gtggcttccc atgctcgcaa gccctggccc gagttcgagc acaatgtcat 3300
gaccaggtgc aatatgcatc tggggtcccg gcgatcgccc gaggcatgtt catgccctac 3360
cagtgcaaca tgcaatttgt gaaggtgctg ctggagcccg atgccatgtc cagagtgagc 3420
ctgacggggg tgtttgacat gaatgtggag ctgtggaaaa ttctgagata tgatgaatcc 3480
aagaccaggt gccgggcctg cgaatgcgga ggcaagcacg ccaggcttca gcccgtgtgt 3540
gtggaggtga cggaggacct gcgacccgat catttggtgt tgtcctgcaa cgggacggag 3600
ttcggctcca gcggggaaga atctgactag agtgagtagt gtttgggggt gggtgggagc 3660
ctgcatgatg ggcagaatga ctaaaatctg tgtttttctg tgtgttgcag cagcatgagc 3720
ggaagcgcct cctttgaggg aggggtattc agcccttatc tgacggggcg tctcccctcc 3780
tgggcgggag tgcgtcagaa tgtgatggga tccacggtgg acggccggcc cgtgcagccc 3840
gcgaactctt caaccctgac ctacgcgacc ctgagctcct cgtccgtgga cgcagctgcc 3900
gccgcagctg ctgcttccgc cgccagcgcc gtgcgcggaa tggccctggg cgccggctac 3960
tacagctctc tggtggccaa ctcgagttcc accaataatc ccgccagcct gaacgaggag 4020
aagctgttgc tgctgatggc ccagctcgag gccctgaccc agcgcctggg cgagctgacc 4080
cagcaggtgg ctcagctgca ggcggagacg cgggccgcgg ttgccacggt gaaaaccaaa 4140
taaaaaatga atcaataaat aaacggagac ggttgttgat tttaacacag agtcttgaat 4200
ctttatttga tttttcgcgc gcggtaggcc ctggaccacc ggtctcgatc attgagcacc 4260
cggtggatct tttccaggac ccggtagagg tgggcttgga tgttgaggta catgggcatg 4320
agcccgtccc gggggtggag gtagctccat tgcagggcct cgtgctcggg ggtggtgttg 4380
taaatcaccc agtcatagca ggggcgcagg gcgtggtgct gcacgatgtc tttgaggagg 4440
agactgatgg ccacgggcag ccccttggtg taggtgttga cgaacctatt gagctgggag 4500
ggatgcatgc ggggggagat gagatgcatc ttggcctgga tcttgagatt ggcgatgttc 4560
ccgcccagat cccgccgggg gttcatgttg tgcaggacca ccagcacggt gtatccggtg 4620
cacttgggga atttgtcatg caacttggaa gggaaggcgt gaaagaattt ggagacgccc 4680
ttgtgaccgc ccaggttttc catgcactca tccatgatga tggcgatggg cccgtgggcg 4740
gcggcctggg caaagacgtt tcgggggtcg gacacatcgt agttgtggtc ctgggtgagc 4800
tcgtcatagg ccattttaat gaatttgggg cggagggtac ccgactgggg gacaaaggtg 4860
ccctcgatcc cgggggcgta gttcccctcg cagatctgca tctcccaggc cttgagctcg 4920
gaggggggga tcatgtccac ctgcggggcg atgaaaaaaa cggtttccgg ggcgggggag 4980
atgagctgcg ccgaaagcag gttccggagc agctgggact tgccgcagcc ggtggggccg 5040
tagatgaccc cgatgaccgg ctgcaggtgg tagttgaggg agagacagct gccgtcctcg 5100
cggaggaggg gggccacctc gttcatcatc tcgcgcacat gcatgttctc gcgcacgagt 5160
tccgccagga ggcgctcgcc ccccagcgag aggagctctt gcagcgaggc gaagtttttc 5220
agcggcttga gcccgtcggc catgggcatt ttggagaggg tctgttgcaa gagttccaga 5280
cggtcccaga gctcggtgat gtgctctagg gcatctcgat ccagcagacc tcctcgtttc 5340
gcgggttggg gcgactgcgg gagtagggca ccaggcgatg ggcgtccagc gaggccaggg 5400
tccggtcctt ccagggtcgc agggtccgcg tcagcgtggt ctccgtcacg gtgaaggggt 5460
gcgcgccggg ctgggcgctt gcgagggtgc gcttcaggct catccggctg gtcgagaacc 5520
gctcccggtc ggcgccctgc gcgtcggcca ggtagcaatt gagcatgagt tcgtagttga 5580
gcgcctcggc cgcgtggccc ttggcgcgga gcttaccttt ggaagtgtgt ccgcagacgg 5640
gacagaggag ggacttgagg gcgtagagct tgggggcgag gaagacggac tcgggggcgt 5700
aggcgtccgc gccgcagctg gcgcagacgg tctcgcactc cacgagccag gtgaggtcgg 5760
ggcggtcggg gtcaaaaacg aggtttcctc cgtgcttttt gatgcgtttc ttacctctgg 5820
tctccatgag ctcgtgtccc cgctgggtga caaagaggct gtccgtgtcc ccgtagaccg 5880
actttatggg ccggtcctcg agcggggtgc cgcggtcctc gtcgtagagg aaccccgccc 5940
actccgagac gaaggcccgg gtccaggcca gcacgaagga ggccacgtgg gaggggtagc 6000
ggtcgttgtc caccagcggg tccaccttct ccagggtatg caagcacatg tccccctcgt 6060
ccacatccag gaaggtgatt ggcttgtaag tgtaggccac gtgaccgggg gtcccggccg 6120
ggggggtata aaagggggcg ggcccctgct cgtcctcact gtcttccgga tcgctgtcca 6180
ggagcgccag ctgttggggt aggtattccc tctcgaaggc gggcatgacc tcggcactca 6240
ggttgtcagt ttctagaaac gaggaggatt tgatattgac ggtgccgttg gagacgcctt 6300
tcatgagccc ctcgtccatc tggtcagaaa agacgatctt tttgttgtcg agcttggtgg 6360
cgaaggagcc gtagagggcg ttggagagca gcttggcgat ggagcgcatg gtctggttct 6420
tttccttgtc ggcgcgctcc ttggcggcga tgttgagctg cacgtactcg cgcgccacgc 6480
acttccattc ggggaagacg gtggtgagct cgtcgggcac gattctgacc cgccagccgc 6540
ggttgtgcag ggtgatgagg tccacgctgg tggccacctc gccgcgcagg ggctcgttgg 6600
tccagcagag gcgcccgccc ttgcgcgagc agaagggggg cagcgggtcc agcatgagct 6660
cgtcgggggg gtcggcgtcc acggtgaaga tgccgggcag gagctcgggg tcgaagtagc 6720
tgatgcaggt gcccagatcg tccagacttg cttgccagtc gcgcacggcc agcgcgcgct 6780
cgtaggggct gaggggcgtg ccccagggca tggggtgcgt gagcgcggag gcgtacatgc 6840
cgcagatgtc gtagacgtag aggggctcct ggaggacgcc gatgtaggtg gggtagcagc 6900
gccccccgcg gatgctggcg cgcacgtagt cgtacagctc gtgcgagggc gcgaggagcc 6960
ccgtgccgag attggagcgc tgcggctttt cggcgcggta gacgatctgg cggaagatgg 7020
cgtgggagtt ggaggagatg gtgggcctct ggaagatgtt gaagtgggca tggggcagtc 7080
cgaccgagtc cctgatgaag tgggcgtagg agtcctgcag cttggcgacg agctcggcgg 7140
tgacgaggac gtccagggcg cagtagtcga gggtctcttg gatgatgtcg tacttgagct 7200
ggcccttctg cttccacagc tcgcggttga gaaggaactc ttcgcggtcc ttccagtact 7260
cttcgagggg gaacccgtcc tgatcggcac ggtaagagcc caccatgtag aactggttga 7320
cggccttgta ggcgcagcag cccttctcca cggggagggc gtaagcttgc gcggccttgc 7380
gcagggaggt gtgggtgagg gcgaaggtgt cgcgcaccat gactttgagg aactggtgct 7440
tgaagtcgag gtcgtcgcag ccgccctgct cccagagctg gaagtccgtg cgcttcttgt 7500
aggcggggtt gggcaaagcg aaagtaacat cgttgaagag gatcttgccc gcgcggggca 7560
tgaagttgcg agtgatgcgg aaaggctggg gcacctcggc ccggttgttg atgacctggg 7620
cggcgaggac gatctcgtcg aagccgttga tgttgtgccc gacgatgtag agttccacga 7680
atcgcgggcg gcccttgacg tggggcagct tcttgagctc gtcgtaggtg agctcggcgg 7740
ggtcgctgag cccgtgctgc tcgagggccc agtcggcgac gtgggggttg gcgctgagga 7800
aggaagtcca gagatccacg gccagggcgg tctgcaagcg gtcccggtac tgacggaact 7860
gctggcccac ggccattttt tcgggggtga cgcagtagaa ggtgcggggg tcgccgtgcc 7920
agcggtccca cttgagctgg agggcgaggt cgtgggcgag ctcgacgagc ggcgggtccc 7980
cggagagttt catgaccagc atgaagggga cgagctgctt gccgaaggac cccatccagg 8040
tgtaggtttc cacatcgtag gtgaggaaga gcctttcggt gcgaggatgc gagccgatgg 8100
ggaagaactg gatctcctgc caccagttgg aggaatggct gttgatgtga tggaagtaga 8160
aatgccgacg gcgcgccgag cactcgtgct tgtgtttata caagcgtccg cagtgctcgc 8220
aacgctgcac gggatgcacg tgctgcacga gctgtacctg ggttcctttg acgaggaatt 8280
tcagtgggca gtggagcgct ggcggctgca tctggtgctg tactacgtcc tggccatcgg 8340
cgtggccatc gtctgcctcg atggtggtca tgctgacgag cccgcgcggg aggcaggtcc 8400
agacctcggc tcggacgggt cggagagcga ggacgagggc gcgcaggccg gagctgtcca 8460
gggtcctgag acgctgcgga gtcaggtcag tgggcagcgg cggcgcgcgg ttgacttgca 8520
ggagcttttc cagggcgcgc gggaggtcca gatggtactt gatctccacg gcgccgttgg 8580
tggcgacgtc cacggcttgc agggtcccgt gcccctgggg cgccaccacc gtgccccgtt 8640
tcttcttggg cggcggcggc tccatgctta gaagcggcgg cgaggacgcg cgccgggcgg 8700
caggggcggc tcggggcccg gaggcagggg cggcaggggc acgtcggcgc cgcgcgcggg 8760
caggttctgg tactgcgccc ggagaagact ggcgtgagcg acgacgcgac ggttgacgtc 8820
ctggatctga cgcctctggg tgaaggccac gggacccgtg agtttgaacc tgaaagagag 8880
ttcgacagaa tcaatctcgg tatcgttgac ggcggcctgc cgcaggatct cttgcacgtc 8940
gcccgagttg tcctggtagg cgatctcggt catgaactgc tcgatctcct cctcctgaag 9000
gtctccgcgg ccggcgcgct cgacggtggc cgcgaggtcg ttggagatgc ggcccatgag 9060
ctgcgagaag gcgttcatgc cggcctcgtt ccagacgcgg ctgtagacca cggctccgtc 9120
ggggtcgcgc gcgcgcatga ccacctgggc gaggttgagc tcgacgtggc gcgtgaagac 9180
cgcgtagttg cagaggcgct ggtagaggta gttgagcgtg gtggcgatgt gctcggtgac 9240
gaagaagtac atgatccagc ggcggagcgg catctcgctg acgtcgccca gggcttccaa 9300
gcgctccatg gcctcgtaga agtccacggc gaagttgaaa aactgggagt tgcgcgccga 9360
gacggtcaac tcctcctcca gaagacggat gagctcggcg atggtggcgc gcacctcgcg 9420
ctcgaaggcc ccggggggct cctcttccat ttcctcctct tcctcctcca ctaacatctc 9480
ttctacttcc tcctcaggag gcggcggcgg gggaggggcc ctgcgtcgcc ggcggcgcac 9540
gggcagacgg tcgatgaagc gctcgatggt ctccccgcgc cggcgacgca tggtctcggt 9600
gacggcgcgc ccgtcctcgc ggggccgcag cgtgaagacg ccgccgcgca tctccaggtg 9660
gccgccgggg gggtctccgt tgggcaggga gagggcgctg acgatgcatc ttatcaattg 9720
acccgtaggg actccgcgca aggacctgag cgtctcgaga tccacgggat ccgaaaaccg 9780
ctgaacgaag gcttcgagcc agtcgcagtc gcaaggtagg ctgagcccgg tttcttgttc 9840
ttcgggtatt tggtcgggag gcgggcgggc gatgctgctg gtgatgaagt tgaagtaggc 9900
ggtcctgaga cggcggatgg tggcgaggag caccaggtcc ttgggcccgg cttgctggat 9960
gcgcagacgg tcggccatgc cccaggcgtg gtcctgacac ctggcgaggt ccttgtagta 10020
gtcctgcatg agccgctcca cgggcacctc ctcctcgccc gcgcggccgt gcatgcgcgt 10080
gagcccgaac ccgcgctgcg gctggacgag cgccaggtcg gcgacgacgc gctcggcgag 10140
gatggcctgc tggatctggg tgagggtggt ctggaagtcg tcgaagtcga cgaagcggtg 10200
gtaggctccg gtgttgatgg tgtaggagca gttggccatg acggaccagt tgacggtctg 10260
gtggccgggg cgcacgagct cgtggtactt gaggcgcgag taggcgcgcg tgtcgaagat 10320
gtagtcgttg caggtgcgca cgaggtactg gtatccgacg aggaagtgcg gcggcggctg 10380
gcggtagagc ggccatcgct cggtggcggg ggcgccgggc gcgaggtcct cgagcatgag 10440
gcggtggtag ccgtagatgt acctggacat ccaggtgatg ccggcggcgg tggtggaggc 10500
gcgcgggaac tcgcggacgc ggttccagat gttgcgcagc ggcaggaagt agttcatggt 10560
ggccgcggtc tggcccgtga ggcgcgcgca gtcgtggatg ctctagacat acgggcaaaa 10620
acgaaagcgg tcagcggctc gactccgtgg cctggaggct aagcgaacgg gttgggctgc 10680
gcgtgtaccc cggttcgaat ctcgaatcag gctggagccg cagctaacgt ggtactggca 10740
ctcccgtctc gacccaagcc tgctaacgaa acctccagga tacggaggcg ggtcgttttt 10800
tggccttggt cgctggtcat gaaaaactag taagcgcgga aagcggccgc ccgcgatggc 10860
tcgctgccgt agtctggaga aagaatcgcc agggttgcgt tgcggtgtgc cccggttcga 10920
gcctcagcgc tcggcgccgg ccggattccg cggctaacgt gggcgtggct gccccgtcgt 10980
ttccaagacc ccttagccag ccgacttctc cagttacgga gcgagcccct ctttttttct 11040
tgtgtttttg ccagatgcat cccgtactgc ggcagatgcg cccccaccct ccaccacaac 11100
cgcccctacc gcagcagcag caacagccgg cgcttctgcc cccgccccag cagcagcagc 11160
cagccactac cgcggcggcc gccgtgagcg gagccggcgt tcagtatgac ctggccttgg 11220
aagagggcga ggggctggcg cggctggggg cgtcgtcgcc ggagcggcac ccgcgcgtgc 11280
agatgaaaag ggacgctcgc gaggcctacg tgcccaagca gaacctgttc agagacagga 11340
gcggcgagga gcccgaggag atgcgcgcct cccgcttcca cgcggggcgg gagctgcggc 11400
gcggcctgga ccgaaagcgg gtgctgaggg acgaggattt cgaggcggac gagctgacgg 11460
ggatcagccc cgcgcgcgcg cacgtggccg cggccaacct ggtcacggcg tacgagcaga 11520
ccgtgaagga ggagagcaac ttccaaaaat ccttcaacaa ccacgtgcgc acgctgatcg 11580
cgcgcgagga ggtgaccctg ggcctgatgc acctgtggga cctgctggag gccatcgtgc 11640
agaaccccac gagcaagccg ctgacggcgc agctgtttct ggtggtgcag cacagtcggg 11700
acaacgagac gttcagggag gcgctgctga atatcaccga gcccgagggc cgctggctcc 11760
tggacctggt gaacattctg cagagcatcg tggtgcagga gcgcgggctg ccgctgtccg 11820
agaagctggc ggccatcaac ttctcggtgc tgagcctggg caagtactac gctaggaaga 11880
tctacaagac cccgtacgtg cccatagaca aggaggtgaa gatcgatggg ttttacatgc 11940
gcatgaccct gaaagtgctg accctgagcg acgatctggg ggtgtaccgc aacgacagga 12000
tgcaccgcgc ggtgagcgcc agccgccggc gcgagctgag cgaccaggag ctgatgcaca 12060
gcctgcagcg ggccctgacc ggggccggga ccgaggggga gagctacttt gacatgggcg 12120
cggacctgcg ctggcagccc agccgccggg ccttggaagc tgccggcggc gtgccctacg 12180
tggaggaggt ggacgatgag gaggaggagg gcgagtacct ggaagactga tggcgcgacc 12240
gtatttttgc tagatgcagc aacagccacc gccgccgcct cctgatcccg cgatgcgggc 12300
ggcgctgcag agccagccgt ccggcattaa ctcctcggac gattggaccc aggccatgca 12360
acgcatcatg gcgctgacga cccgcaatcc cgaagccttt agacagcagc ctcaggccaa 12420
ccggctctcg gccatcctgg aggccgtggt gccctcgcgc tcgaacccca cgcacgagaa 12480
ggtgctggcc atcgtgaacg cgctggtgga gaacaaggcc atccgcggcg acgaggccgg 12540
gctggtgtac aacgcgctgc tggagcgcgt ggcccgctac aacagcacca acgtgcagac 12600
gaacctggac cgcatggtga ccgacgtgcg cgaggcggtg tcgcagcgcg agcggttcca 12660
ccgcgagtcg aacctgggct ccatggtggc gctgaacgcc ttcctgagca cgcagcccgc 12720
caacgtgccc cggggccagg aggactacac caacttcatc agcgcgctgc ggctgatggt 12780
ggccgaggtg ccccagagcg aggtgtacca gtcggggccg gactacttct tccagaccag 12840
tcgccagggc ttgcagaccg tgaacctgag ccaggctttc aagaacttgc agggactgtg 12900
gggcgtgcag gccccggtcg gggaccgcgc gacggtgtcg agcctgctga cgccgaactc 12960
gcgcctgctg ctgctgctgg tggcgccctt cacggacagc ggcagcgtga gccgcgactc 13020
gtacctgggc tacctgctta acctgtaccg cgaggccatc gggcaggcgc acgtggacga 13080
gcagacctac caggagatca cccacgtgag ccgcgcgctg ggccaggagg acccgggcaa 13140
cctggaggcc accctgaact tcctgctgac caaccggtcg cagaagatcc cgccccagta 13200
cgcgctgagc accgaggagg agcgcatcct gcgctacgtg cagcagagcg tggggctgtt 13260
cttgatgcag gagggggcca cgcccagcgc cgcgctcgac atgaccgcgc gcaacatgga 13320
gcccagcatg tacgcccgca accgcccgtt catcaataag ctgatggact acttgcatcg 13380
ggcggccgcc atgaactcgg actactttac caacgccatc ttgaacccgc actggctccc 13440
gccgcccggg ttctacacgg gcgagtacga catgcccgac cccaacgacg ggttcctgtg 13500
ggacgacgtg gacagcagcg tgttctcgcc gcggcccacc accaccaccg tgtggaagaa 13560
agagggcggg gaccggcggc cgtcctcggc gctgtccggt cgcgcgggtg ctgccgcggc 13620
ggtgcccgag gctgccagcc ccttcccgag cctgcccttt tcgctgaaca gcgtgcgcag 13680
cagcgagctg ggtcggctga cgcggccgcg cctgctgggc gaggaggagt acctgaacga 13740
ctccttgttg aagcccgagc gcgagaagaa cttccccaat aacgggatag agagcctggt 13800
ggacaagatg agccgctgga agacgtacgc gcacgagcac agggacgagc cccgagctag 13860
cagcgcaggc acccgtagac gccagcggca cgacaggcag cggggactgg tgtgggacga 13920
tgaggattcc gccgacgaca gcagcgtgtt ggacttgggt gggagtggtg gtggtaaccc 13980
gttcgctcac ctgcgccccc gtatcgggcg cctgatgtaa gaatctgaaa aaataaaaga 14040
cggtactcac caaggccatg gcgaccagcg tgcgttcttc tctgttgttt gtagtagtat 14100
gatgaggcgc gtgtacccgg agggtcctcc tccctcgtac gagagcgtga tgcagcaggc 14160
ggtggcggcg gcgatgcagc ccccgctgga ggcgccttac gtgcccccgc ggtacctggc 14220
gcctacggag gggcggaaca gcattcgtta ctcggagctg gcacccttgt acgataccac 14280
ccggttgtac ctggtggaca acaagtcggc ggacatcgcc tcgctgaact accagaacga 14340
ccacagcaac ttcctgacca ccgtggtgca gaacaacgat ttcaccccca cggaggccag 14400
cacccagacc atcaactttg acgagcgctc gcggtggggc ggccagctga aaaccatcat 14460
gcacaccaac atgcccaacg tgaacgagtt catgtacagc aacaagttca aggcgcgggt 14520
gatggtctcg cgcaagaccc ccaacggggt cacggtaggg gatgattatg atggtagtca 14580
ggacgagctg acctacgagt gggtggagtt tgagctgccc gagggcaact tctcggtgac 14640
catgaccatc gatctgatga acaacgccat catcgacaac tacttggcgg tggggcggca 14700
gaacggggtg ctggagagcg acatcggcgt gaagttcgac acgcgcaact tccggctggg 14760
ctgggacccc gtgaccgagc tggtgatgcc gggcgtgtac accaacgagg ccttccaccc 14820
cgacatcgtc ctgctgcccg gctgcggcgt ggacttcacc gagagccgcc tcagcaacct 14880
gctgggcatc cgcaagcggc agcccttcca ggagggcttc cagatcctgt acgaggacct 14940
ggaggggggc aacatccccg cgctcttgga tgtcgaagcc tatgaagaaa gtaaggaaaa 15000
agcagaggct gaggcaacta cagccgtggc taccgccgcg actgtggcag atgccactgt 15060
caccaggggc gatacattcg ccacccaggc ggaggaagca gccgccctag cggcgaccga 15120
tgatagtgaa agtaagatag tcatcaagcc ggtggagaag gacagcaaga acaggagcta 15180
caacgttcta ccggatggaa agaacaccgc ctaccgcagc tggtacctgg cctacaacta 15240
cggcgacccc gagaagggcg tgcgctcctg gacgctgctc accacctcgg acgtcacctg 15300
cggcgtggag caagtctact ggtcgctgcc cgacatgatg caagacccgg tcaccttccg 15360
ctccacgcga caagttagca actacccggt ggtgggcgcc gagctcctgc ccgtctactc 15420
caagagcttc ttcaacgagc aggccgtcta ctcgcagcag ctgcgtgcct tcacctcgct 15480
cacgcacgtc ttcaaccgct tccccgagaa ccagatcctc gtccgcccgc ccgcgcccac 15540
cattaccacc gtcagtgaaa acgttcctgc tctcacagat cacgggaccc tgccgctgcg 15600
cagcagtatc cggggagtcc agcgcgtgac cgtcactgac gccagacgcc gcacctgccc 15660
ctacgtctac aaggccctgg gcgtagtcgc gccgcgcgtc ctctcgagcc gcaccttcta 15720
aaaaatgtcc attctcatct cgcccagtaa taacaccggt tggggcctgc gcgcgcccag 15780
caagatgtac ggaggcgctc gccaacgctc cacgcaacac cccgtgcgcg tgcgcgggca 15840
cttccgcgct ccctggggcg ccctcaaggg ccgcgtgcgc tcgcgcacca ccgtcgacga 15900
cgtgatcgac caggtggtgg ccgacgcgcg caactacacg cccgccgccg cgcccgcctc 15960
caccgtggac gccgtcatcg acagcgtggt ggccgacgcg cgccggtacg cccgcgccaa 16020
gagccggcgg cggcgcatcg cccggcggca ccggagcacc cccgccatgc gcgcggcgcg 16080
agccttgctg cgcagggcca ggcgcacggg acgcagggcc atgctcaggg cggccagacg 16140
cgcggcctcc ggcagcagca gcgccggcag gacccgcaga cgcgcggcca cggcggcggc 16200
ggcggccatc gccagcatgt cccgcccgcg gcgcggcaac gtgtactggg tgcgcgacgc 16260
cgccaccggt gtgcgcgtgc ccgtgcgcac ccgcccccct cgcacttgaa gatgctgact 16320
tcgcgatgtt gatgtgtccc agcggcgagg aggatgtcca agcgcaaata caaggaagag 16380
atgctccagg tcatcgcgcc tgagatctac ggccccgcgg cggcggtgaa ggaggaaaga 16440
aagccccgca aactgaagcg ggtcaaaaag gacaaaaagg aggaggaaga tgacggactg 16500
gtggagtttg tgcgcgagtt cgccccccgg cggcgcgtgc agtggcgcgg gcggaaagtg 16560
aaaccggtgc tgcggcccgg caccacggtg gtcttcacgc ccggcgagcg ttccggctcc 16620
gcctccaagc gctcctacga cgaggtgtac ggggacgagg acatcctcga gcaggcggtc 16680
gagcgtctgg gcgagtttgc ttacggcaag cgcagccgcc ccgcgccctt gaaagaggag 16740
gcggtgtcca tcccgctgga ccacggcaac cccacgccga gcctgaagcc ggtgaccctg 16800
cagcaggtgc tgccgagcgc ggcgccgcgc cggggcttca agcgcgaggg cggcgaggat 16860
ctgtacccga ccatgcagct gatggtgccc aagcgccaga agctggagga cgtgctggag 16920
cacatgaagg tggaccccga ggtgcagccc gaggtcaagg tgcggcccat caagcaggtg 16980
gccccgggcc tgggcgtgca gaccgtggac atcaagatcc ccacggagcc catggaaacg 17040
cagaccgagc ccgtgaagcc cagcaccagc accatggagg tgcagacgga tccctggatg 17100
ccagcggctt ccaccaccac cactcgccga agacgcaagt acggcgcggc cagcctgctg 17160
atgcccaact acgcgctgca tccttccatc atccccacgc cgggctaccg cggcacgcgc 17220
ttctaccgcg gctacaccag cagccgccgc cgcaagacca ccacccgccg ccgtcgtcgc 17280
agccgccgca gcagcaccgc gacttccgcc ttggtgcgga gagtgtatcg cagcgggcgc 17340
gagcctctga ccctgccgcg cgcgcgctac cacccgagca tcgccattta actaccgcct 17400
cctacttgca gatatggccc tcacatgccg cctccgcgtc cccattacgg gctaccgagg 17460
aagaaagccg cgccgtagaa ggctgacggg gaacgggctg cgtcgccatc accaccggcg 17520
gcggcgcgcc atcagcaagc ggttgggggg aggcttcctg cccgcgctga tccccatcat 17580
cgccgcggcg atcggggcga tccccggcat agcttccgtg gcggtgcagg cctctcagcg 17640
ccactgagac acaaaaaagc atggatttgt aataaaaaaa tggactgacg ctcctggtcc 17700
tgtgatgtgt gtttttagat ggaagacatc aatttttcgt ccctggcacc gcgacacggc 17760
acgcggccgt ttatgggcac ctggagcgac atcggcaaca gccaactgaa cgggggcgcc 17820
ttcaattgga gcagtctctg gagcgggctt aagaatttcg ggtccacgct caaaacctat 17880
ggcaacaagg cgtggaacag cagcacaggg caggcgctga gggaaaagct gaaagagcag 17940
aacttccagc agaaggtggt cgatggcctg gcctcgggca tcaacggggt ggtggacctg 18000
gccaaccagg ccgtgcagaa acagatcaac agccgcctgg acgcggtccc gcccgcgggg 18060
tccgtggaga tgccccaggt ggaggaggag ctgcctcccc tggacaagcg cggcgacaag 18120
cgaccgcgtc ccgacgcgga ggagacgctg ctgacgcaca cggacgagcc gcccccgtac 18180
gaggaggcgg tgaaactggg tctgcccacc acgcggcccg tggcgcctct ggccaccggg 18240
gtgctgaaac ccagcagcag cagccagccc gcgaccctgg acttgcctcc gcctgcttcc 18300
cgcccctcca cagtggctaa gcccctgccg ccggtggccg tcgcgtcgcg cgccccccga 18360
ggccgccccc aggcgaactg gcagagcact ctgaacagca tcgtgggtct gggagtgcag 18420
agtgtgaagc gccgccgctg ctattaaaag acactgtagc gcttaacttg cttgtctgtg 18480
tgtgtatatg tatgtccgcc gaccagaagg aggaagaggc gcgtcgccga gttgcaagat 18540
ggccacccca tcgatgctgc cccagtgggc gtacatgcac atcgccggac aggacgcttc 18600
ggagtacctg agtccgggtc tggtgcagtt cgcccgcgcc acagacacct acttcagtct 18660
ggggaacaag tttaggaacc ccacggtggc gcccacgcac gatgtgacca ccgaccgcag 18720
ccagcggctg acgctgcgct tcgtgcccgt ggaccgcgag gacaacacct actcgtacaa 18780
agtgcgctac acgctggccg tgggcgacaa ccgcgtgctg gacatggcca gcacctactt 18840
tgacatccgc ggcgtgctgg atcggggccc cagcttcaaa ccctactccg gcaccgccta 18900
caacagccta gctcccaagg gagcgcccaa cacctcacag tggaaggatt ccgacagcaa 18960
aatgcatact tttggagttg ctgccatgcc cggtgttgtt ggtaaaaaaa tagaagccga 19020
tggtctgcct attggaatag attcatcctc tggaactgac accataattt atgctgataa 19080
aactttccaa ccagagccac aggttggaag tgacagttgg gtcgacacca atggtgcaga 19140
ggaaaaatat ggaggtagag ctcttaagga cactacaaac atgaagccct gctacggttc 19200
ttttgccagg cctaccaaca aagaaggtgg acaggctaac ataaaagatt ctgaaactgc 19260
cagcactact cctaactatg atatagattt ggcattcttt gacagcaaaa atattgcagc 19320
taactacgat ccagatattg taatgtacac agaaaatgtt gagttgcaaa ctccagatac 19380
tcatattgtg tttaagccag gaacttcaga tgaaagttca gaagccaatt tgggccagca 19440
ggccatgccc aacagaccca actacatcgg gttcagagac aactttatcg ggctcatgta 19500
ctacaacagc actggcaata tgggtgtact ggctggtcag gcctcccagc taaatgctgt 19560
ggtggacttg caggacagaa acaccgaact gtcctaccag ctcttgcttg actctctggg 19620
tgacagaacc aggtatttca gtatgtggaa tcaggcggtg gacagctatg accccgatgt 19680
gcgcattatt gaaaatcacg gtgtggagga tgaactcccc aattattgct tccctttgaa 19740
tggtgtaggc tttacagata cttaccaggg tgttaaagtt aagacagata cagccgctac 19800
tggtaccaat ggaacgcagt gggacaaaga tgataccaca gtcagcactg ccaatgagat 19860
ccactcaggc aatcctttcg ccatggagat caacatccag gccaacctgt ggcggaactt 19920
cctctacgcg aacgtggcgc tgtacctgcc cgactcctac aagtacacgc cggccaacat 19980
cacgctgccg accaacacca acacctacga ttacatgaac ggccgcgtgg tggcgccctc 20040
gctggtggac gcctacatca acatcggggc gcgctggtcg ctggacccca tggacaacgt 20100
caaccccttc aaccaccacc gcaacgcggg cctgcgctac cgctccatgc tcctgggcaa 20160
cgggcgctac gtgcccttcc acatccaggt gccccaaaag tttttcgcca tcaagagcct 20220
cctgctcctg cccgggtcct acacctacga gtggaacttc cgcaaggacg tcaacatgat 20280
cctgcagagc tccctcggca acgacctgcg cacggacggg gcctccatcg ccttcaccag 20340
catcaacctc tacgccacct tcttccccat ggcgcacaac accgcctcca cgctcgaggc 20400
catgctgcgc aacgacacca acgaccagtc cttcaacgac tacctctcgg cggccaacat 20460
gctctacccc atcccggcca acgccaccaa cgtgcccatc tccatcccct cgcgcaactg 20520
ggccgccttc cgcggatggt ccttcacgcg cctcaagacc cgcgagacgc cctcgctcgg 20580
ctccgggttc gacccctact tcgtctactc gggctccatc ccctacctcg acggcacctt 20640
ctacctcaac cacaccttca agaaggtctc catcaccttc gactcctccg tcagctggcc 20700
cggcaacgac cgcctcctga cgcccaacga gttcgaaatc aagcgcaccg tcgacggaga 20760
gggatacaac gtggcccagt gcaacatgac caaggactgg ttcctggtcc agatgctggc 20820
ccactacaac atcggctacc agggcttcta cgtgcccgag ggctacaagg accgcatgta 20880
ctccttcttc cgcaacttcc agcccatgag ccgccaggtc gtggacgagg tcaactacaa 20940
ggactaccag gccgtcaccc tggcctacca gcacaacaac tcgggcttcg tcggctacct 21000
cgcgcccacc atgcgccagg gccagcccta ccccgccaac tacccctacc cgctcatcgg 21060
caagagcgcc gtcgccagcg tcacccagaa aaagttcctc tgcgaccggg tcatgtggcg 21120
catccccttc tccagcaact tcatgtccat gggcgcgctc accgacctcg gccagaacat 21180
gctctacgcc aactccgccc acgcgctaga catgaatttc gaagtcgacc ccatggatga 21240
gtccaccctt ctctatgttg tcttcgaagt cttcgacgtc gtccgagtgc accagcccca 21300
ccgcggcgtc atcgaggccg tctacctgcg cacgcccttc tcggccggca acgccaccac 21360
ctaaagcccc gctcttgctt cttgcaagat gacggcctgt ggctccggcg agcaggagct 21420
cagggccatc ctccgcgacc tgggctgcgg gccctgcttc ctgggcacct tcgacaagcg 21480
cttcccggga ttcatggccc cgcacaagct ggcctgcgcc atcgtcaaca cggccggccg 21540
cgagaccggg ggcgagcact ggctggcctt cgcctggaac ccgcgctccc acacctgcta 21600
cctcttcgac cccttcgggt tctcggacga gcgcctcaag cagatctacc agttcgagta 21660
cgagggcctg ctgcgccgca gcgccctggc caccgaggac cgctgcatca ccctggaaaa 21720
gtccacccag accgtgcagg gtccgcgctc ggccgcctgc gggctcttct gctgcatgtt 21780
cctgcacgcc ttcgtgcact ggcccgaccg ccccatggac aagaacccca ccatgaactt 21840
gctgacgggg gtgcccaacg gcatgctcca gtcgccccag gtggaaccca ccctgcgccg 21900
caaccaggag gcgctctacc gcttcctcaa cgcccactcc gcctactttc gctcccaccg 21960
cgcgcgcatc gagaaggcca ccgccttcga ccgcatgaat caagacatgt aaactgtgtg 22020
tatgtgaatg ctttattcat cataataaac agcacatgtt tatgccacct tctctgaggc 22080
tctgacttta tttagaaatc gaaggggttc tgccggctct cggcgtgccc cgcgggcagg 22140
gatacgttgc ggaactggta cttgggcagc cacttgaact cggggatcag cagcttcggc 22200
acggggaggt cggggaacga gtcgctccac agcttgcgcg tgagttgcag ggcgcccagc 22260
aggtcgggcg cggagatctt gaaatcgcag ttgggacccg cgttctgcgc gcgagagttg 22320
cggtacacgg ggttgcagca ctggaacacc atcagggccg ggtgcttcac gctcgccagc 22380
accgtcgcgt cggtgatgcc ctccacgtcc agatcctcgg cgttggccat cccgaagggg 22440
gtcatcttgc aggtctgccg ccccatgctg ggcacgcagc cgggcttgtg gttgcaatcg 22500
cagtgcaggg ggatcagcat catctgagcc tgctcggagc tcatgcccgg gtacatggcc 22560
ttcatgaaag cctccagctg gcggaaggcc tgctgcgcct tgccgccctc ggtgaagaag 22620
accccacagg acttgctaga gaactggttg gtggcgcagc ccgcgtcgtg cacgcagcag 22680
cgcgcgtcgt tgttggccag ctgcaccacg ctgcgccccc agcggttctg ggtgatcttg 22740
gcccggtcgg ggttctcctt cagcgcgcgc tgcccgttct cgctcgccac atccatctcg 22800
atcgtgtgct ccttctggat catcacggtc ccgtgcaggc accgcagctt gccctcggcc 22860
tcggtgcacc cgtgcagcca cagcgcgcag ccggtgcact cccagttctt gtgggcgatc 22920
tgggagtgcg agtgcacgaa gccctgcagg aagcggccca tcatcgtggt cagggtcttg 22980
ttgctggtga aggtcagcgg gatgccgcgg tgctcctcgt tcacatacag gtggcagatg 23040
cggcggtaca cctcgccctg ctcgggcatc agctggaagg cggacttcag gtcgctctcc 23100
acgcggtacc gctccatcag cagcgtcatc acttccatgc ccttctccca ggccgaaacg 23160
atcggcaggc tcagggggtt cttcaccgtc atcttagtcg ccgccgccga agtcaggggg 23220
tcgttctcgt ccagggtctc aaacactcgc ttgccgtcct tctcggtgat gcgcacgggg 23280
ggaaagctga agcccacggc cgccagctcc tcctcggcct gcctttcgtc ctcgctgtcc 23340
tggctgatgt cttgcaaagg cacatgcttg gtcttgcggg gtttcttttt gggcggcaga 23400
ggcggcggcg gagacgtgct gggcgagcgc gagttctcgc tcaccacgac tatttcttct 23460
tcttggccgt cgtccgagac cacgcggcgg taggcatgcc tcttctgggg cagaggcgga 23520
ggcgacgggc tctcgcggtt cggcgggcgg ctggcagagc cccttccgcg ttcgggggtg 23580
cgctcctggc ggcgctgctc tgactgactt cctccgcggc cggccattgt gttctcctag 23640
ggagcaacaa gcatggagac tcagccatcg tcgccaacat cgccatctgc ccccgccgcc 23700
gacgagaacc agcagcagca gaatgaaagc ttaaccgccc cgccgcccag ccccacctcc 23760
gacgccgccg cggccccaga catgcaagag atggaggaat ccatcgagat tgacctgggc 23820
tacgtgacgc ccgcggagca cgaggaggag ctggcagcgc gcttttcagc cccggaagag 23880
aaccaccaag agcagccaga gcaggaagca gagagcgagc agcagcaggc tgggctcgag 23940
catggcgact acctgagcgg ggcagaggac gtgctcatca agcatctggc ccgccaaagc 24000
atcatcgtca aggacgcgct gctcgaccgc gccgaggtgc ccctcagcgt ggcggagctc 24060
agccgcgcct acgagcgcaa cctcttctcg ccgcgcgtgc cccccaagcg ccagcccaac 24120
ggcacctgcg agcccaaccc gcgcctcaac ttctacccgg tcttcgcggt gcccgaggcc 24180
ctggccacct accacctctt tttcaagaac caaaggatcc ccgtctcctg ccgcgccaac 24240
cgcacccgcg ccgacgccct gctcaacctg ggtcccggcg cccgcctacc tgatatcacc 24300
tccttggaag aggttcccaa gatcttcgag ggtctgggca gcgacgagac tcgggccgcg 24360
aacgctctgc aaggaagcgg agaggagcat gagcaccaca gcgccctggt ggagttggaa 24420
ggcgacaacg cgcgcctggc ggtgctcaag cgcacggtcg agctgaccca cttcgcctac 24480
ccggcgctca acctgccccc caaggtcatg agcgccgtca tggaccaggt gctcatcaag 24540
cgcgcctcgc ccctctcaga ggaggagatg caggaccccg agagctcgga cgagggcaag 24600
cccgtggtca gcgacgagca gctggcgcgc tggctgggag cgagcagcac cccccagagc 24660
ctggaagagc ggcgcaagct catgatggcc gtggtcctgg tgaccgtgga gctggagtgt 24720
ctgcgccgct tcttcgccga cgcggagacc ctgcgcaagg tcgaggagaa cctgcactac 24780
ctcttcaggc acgggttcgt gcgccaggcc tgcaagatct ccaacgtgga gctgaccaac 24840
ctggtctcct acatgggcat cctgcacgag aaccgcctgg ggcagaacgt gctgcacacc 24900
accctgcgcg gggaggcccg ccgcgactac atccgcgact gcgtctacct gtacctctgc 24960
cacacctggc agacgggcat gggcgtgtgg cagcagtgcc tggaggagca gaacctgaaa 25020
gagctctgca agctcctgca gaagaacctc aaggccctgt ggaccgggtt cgacgagcgc 25080
accaccgcct cggacctggc cgacctcatc ttccccgagc gcctgcggct gacgctgcgc 25140
aacgggctgc ccgactttat gagccaaagc atgttgcaaa actttcgctc tttcatcctc 25200
gaacgctccg ggatcctgcc cgccacctgc tccgcactgc cctcggactt cgtgccgctg 25260
accttccgcg agtgcccccc gccgctctgg agccactgct acttgctgcg cctggccaac 25320
tacctggcct accactcgga cgtgatcgag gacgtcagca gcgagggtct gctcgagtgc 25380
cactgccgct gcaacctctg cacgccgcac cgctccttgg cctgcaaccc ccagctgctg 25440
agcgagaccc agatcatcgg caccttcgag ttgcaaggcc ccggcgaggg caaggggggt 25500
ctcaaactca ccccggggct gtggacctcg gcctacttgc gcaagttcgt gcccgaggac 25560
taccatccct tcgagatcag gttctacgag gaccaatccc agccgcccaa ggccgagctg 25620
tcggcctgcg tcatcaccca gggggccatc ctggcccaat tgcaagccat ccagaaatcc 25680
cgccaagaat ttctgctgaa aaagggccac ggggtctact tggaccccca gaccggagag 25740
gagctcaacc ccagcttccc ccaggatgcc ccgaggaagc agcaagaagc tgaaagtgga 25800
gctgccgctg ccgccggagg atttggagga agactgggag agcagtcagg cagaggagat 25860
ggaagactgg gacagcactc aggcagagga ggacagcctg caagacagtc tggaggagga 25920
agacgaggtg gaggaggagg cagaggaaga agcagccgcc gccagaccgt cgtcctcggc 25980
ggaggagaaa gcaagcagca cggataccat ctccgctccg ggtcggggtc gcggcggccg 26040
ggcccacagt agatgggacg agaccgggcg cttcccgaac cccaccaccc agaccggtaa 26100
gaaggagcgg cagggataca agtcctggcg ggggcacaaa aacgccatcg tctcctgctt 26160
gcaagcctgc gggggcaaca tctccttcac ccggcgctac ctgctcttcc accgcggggt 26220
gaacttcccc cgcaacatct tgcattacta ccgtcacctc cacagcccct actactgttt 26280
ccaagaagag gcagaaaccc agcagcagca gcagaaaacc agcggcagca gcagcagcta 26340
gaaaatccac agcggcggca ggtggactga ggatcgcggc gaacgagccg gcgcagaccc 26400
gggagctgag gaaccggatc tttcccaccc tctatgccat cttccagcag agtcgggggc 26460
aggagcagga actgaaagtc aagaaccgtt ctctgcgctc gctcacccgc agttgtctgt 26520
atcacaagag cgaagaccaa cttcagcgca ctctcgagga cgccgaggct ctcttcaaca 26580
agtactgcgc gctcactctt aaagagtagc ccgcgcccgc ccacacacgg aaaaaggcgg 26640
gaattacgtc accacctgcg cccttcgccc gaccatcatc atgagcaaag agattcccac 26700
gccttacatg tggagctacc agccccagat gggcctggcc gccggcgccg cccaggacta 26760
ctccacccgc atgaactggc tcagtgccgg gcccgcgatg atctcacggg tgaatgacat 26820
ccgcgcccac cgaaaccaga tactcctaga acagtcagcg atcaccgcca cgccccgcca 26880
tcaccttaat ccgcgtaatt ggcccgccgc cctggtgtac caggaaattc cccagcccac 26940
gaccgtacta cttccgcgag acgcccaggc cgaagtccag ctgactaact caggtgtcca 27000
gctggccggc ggcgccgccc tgtgtcgtca ccgccccgct cagggtataa agcggctggt 27060
gatccgaggc agaggcacac agctcaacga cgaggtggtg agctcttcgc tgggtctgcg 27120
acctgacgga gtcttccaac tcgccggatc ggggagatct tccttcacgc ctcgtcaggc 27180
cgtcctgact ttggagagtt cgtcctcgca gccccgctcg ggcggcatcg gcactctcca 27240
gttcgtggag gagttcactc cctcggtcta cttcaacccc ttctccggct cccccggcca 27300
ctacccggac gagttcatcc cgaacttcga cgccatcagc gagtcggtgg acggctacga 27360
ttgaatgtcc catggtggcg cggctgacct agctcggctt cgacacctgg accactgccg 27420
ccgcttccgc tgcttcgctc gggatctcgc cgagtttgcc tactttgagc tgcccgagga 27480
gcaccctcag ggcccggccc acggagtgcg gatcgtcgtc gaagggggcc tcgactccca 27540
cctgcttcgg attttcagcc agcgtccgat cctggtcgag cgcgagcaag gacagaccct 27600
tctgaccctg tactgcatct gcaaccaccc cggcctgcat gaaagtcttt gttgtctgct 27660
gtgtactgag tataataaaa gctgagatca gcgactactc cggactcgat tgtggtgttc 27720
ctgctatcaa ccggtccctg ttcttcaccg ggaacgagac cgagctccag ctccagtgta 27780
agccccacaa gaagtatctc acctggctgt tccagggctc tccgatcgcc gttgtcaacc 27840
actgcgacaa cgacggagtc ctgctgagcg gccctgccaa ccttactttt tccacccgca 27900
gaagcaagct ccagctcttc caacccttcc tccccgggac ctatcagtgc gtctcgggac 27960
cctgccatca caccttccac ctgatcccga ataccacagc gccgctcccc gctactaaca 28020
accaaactac ccaccaacgc caccgtcgcg acctttctga atctaatact accacccaca 28080
ccggaggtga gctccgaggt cgaccaacct ctgggattta ctacggggtt aaccccttaa 28140
ttaaggggat tccatatggt acgtacatcg cctctcctac gagctcctgc agcagcgcca 28200
gaagttcacc tgcctggtcg gagtcaaccc catcgtcatc acccagcagt cgggcgatac 28260
caaggggtgc atccactgct cctgcgactc ccccgactgc gtccacactc tgatcaagac 28320
cctctgcggc ctccgcgacc tcctccccat gaactaatca cccccttatc cagtgaaata 28380
aagatcatat tgatgatgat tttacagaaa taaagataca atcatattga tgatttgagt 28440
ttaataaaaa ataaagaatc acttacttga aatctgatac caggtctctg tccatgtttt 28500
ctgccaacac cacttcactc ccctcttccc agctctggta ctgcaggccc cggcgggctg 28560
caaacttcct ccacacgctg aaggggatgt caaattcctc ctgtccctca atcttcattt 28620
tatcttctat cagatgtcca aaaagcgcgt ccgggtggat gatgacttcg accccgtcta 28680
cccctacgat gcagacaacg caccgaccgt gcccttcatc aaccccccct tcgtctcttc 28740
agatggattc caagagaagc ccctgggggt gctgtccctg cgactggccg accccgtcac 28800
caccaagaac ggggaaatca ccctcaagct gggagagggg gtggacctcg actcctcggg 28860
aaaactcatc tccaacacgg ccaccaaggc cgccgcccct ctcagttttt ccaacaacac 28920
catttccctt aacatggatc acccctttta cactaaagat ggaaaattat ccttacaagt 28980
ttctccacca ttaaatatac tgagaacaag cattctaaac acactagctt taggttttgg 29040
atcaggttta ggactccgtg gctctgcctt ggcagtacag ttagtctctc cacttacatt 29100
tgatactgat ggaaacataa agcttacctt agacagaggt ttgcatgtta caacaggaga 29160
tgcaattgaa agcaacataa gctgggctaa aggtttaaaa tttgaagatg gagccatagc 29220
aaccaacatt ggaaatgggt tagagtttgg aagcagtagt acagaaacag gtgttgatga 29280
tgcttaccca atccaagtta aacttggatc tggccttagc tttgacagta caggagccat 29340
aatggctggt aacaaagaag acgataaact cactttgtgg acaacacctg atccatcgcc 29400
aaactgtcaa atactcgcag aaaatgatgc aaaactaaca ctttgcttga ctaaatgtgg 29460
tagtcaaata ctggccactg tgtcagtctt agttgtagga agtggaaacc taaaccccat 29520
tactggcacc gtaagcagtg ctcaggtgtt tctacgtttt gatgcaaacg gtgttctttt 29580
aacagaacat tctacactaa aaaaatactg ggggtatagg cagggagata gcatagatgg 29640
cactccatat accaatgctg taggattcat gcccaattta aaagcttatc caaagtcaca 29700
aagttctact actaaaaata atatagtagg gcaagtatac atgaatggag atgtttcaaa 29760
acctatgctt ctcactataa ccctcaatgg tactgatgac agcaacagta catattcaat 29820
gtcattttca tacacctgga ctaatggaag ctatgttgga gcaacatttg gggctaactc 29880
ttataccttc tcatacatcg cccaagaatg aacactgtat cccaccctgc atgccaaccc 29940
ttcccacccc actctgtgga aaaaactctg aaacacaaaa taaaataaag ttcaagtgtt 30000
ttattgattc aacagtttta caggattcga gcagttattt ttcctccacc ctcccaggac 30060
atggaataca ccaccctctc cccccgcaca gccttgaaca tctgaacgcc attggtgatg 30120
gacatgcttt tggtctccac gttccacaca gtttcagagc gagccagtct cgggtcggtc 30180
agggagatga aaccctccgg gcacaattgg gagaagtact cgcctattat ctggaagaag 30240
cagaagagcg gcggtgggaa tcatagtccg cgaacgggat cggccggtgg tgtcgcatca 30300
ggccccgcag cagtcgctgc cgccgccgct ccgtcaagct gctgctcagg gggtccgggt 30360
ccagggactc cctcagcatg atgcccacgg ccctcagcat cagtcgtctg gtgcggcggg 30420
cgcagcagcg catgcggatc tcgctcaggt cgctgcagta cgtgcaacac agaaccacca 30480
ggttgttcaa cagtccatag ttcaacacgc tccagccgaa actcatcgcg ggaaggatgc 30540
tacccacgtg gccgtcgtac cagatcctca ggtaaatcaa gtggtgcccc ctccagaaca 30600
cgctgcccac gtacatgatc tccttgggca tgtggcggtt caccacctcc cggtaccaca 30660
tcaccctctg gttgaacatg cagccccgga tgatcctgcg gaaccacagg gccagcaccg 30720
ccccgcccgc catgcagcga agagaccccg ggtcccggca atggcaatgg aggacccacc 30780
gctcgtaccc gtggatcatc tgggagctga acaagtctat gttggcacag cacaggcata 30840
tgctcatgca tctcttcagc actctcaact cctcgggggt caaaaccata tcccagggca 30900
cggggaactc ttgcaggaca gcgaaccccg cagaacaggg caatcctcgc acagaactta 30960
cattgtgcat ggacagggta tcgcaatcag gcagcaccgg gtgatcctcc accagagaag 31020
cgcgggtctc ggtctcctca cagcgtggta agggggccgg ccgatacggg tgatggcggg 31080
acgcggctga tcgtgttcgc gaccgtgtca tgatgcagtt gctttcggac atatttcctg 31140
aagtcttggc gcgccaaagt ctagacagcg tccatagctt accgagcagc agcagcagca 31200
cacaacaggc gcaagagtca gagaaaggct gagctctaac ctgtccaccc gctctctgct 31260
caatatatag cccagatcta cactgacgta aaggccaaag tctaaaaata cccgccaaat 31320
agtcacacac gcccagcaca cgcccagaaa ccggtgacac actcaaaaaa atacgcgcac 31380
ttcctcaaac gcccaaactg ccgtcatttc cgggttccca cgctacgtca tcaaaacacg 31440
actttcaaat tccgtcgacc gttaaaaacg tcacccgccc cgcccctaac ggtcgcccgt 31500
ctctcagcca atcagcgccc cgcatcccca aattcaaaca cctcatttgc atattaacgc 31560
gcaccaaaag tttgaggtat attattgatg atg 31593
<210> 4
<211> 29334
<212> DNA
<213> Artificial sequence (Artificial sequence)
<400> 4
aaatcatcat caataatata cctcaaactt ttggtgcgcg ttaatatgca aatgaggtgt 60
ttgaatttgg ggatgcgggg cgctgattgg ctgagagacg ggcgaccgtt aggggcgggg 120
cgggtgacgt tttgatgacg tggccgtgag gcggagccgg tttgcaagtt ctcgtgggaa 180
aagtgacgtc aaacgaggtg tggtttgaac acggaaatac tcaattttcc cgcgctctct 240
gacaggaaat gaggtgtttc tgggcggatg caagtgaaaa cgggccattt tcgcgcgaaa 300
actgaatgag gaagtgaaaa tctgagtaat tccgcgttta tggcagggag gagtatttgc 360
cgagggccga gtagactttg accgattacg tgggggtttc gattaccgta tttttcacct 420
aaatttccgc gtacggtgtc aaagtccggt gtttttacgt aggcgtcagc tgatcgccag 480
ggtatttaaa cctgcgctct ctagtcaaga ggccactctt gagtgccagc gagtagagtt 540
ttctcctccg cgccgcgagt cagatctaca ctttgaaagg cgatcgccga tatcatttcc 600
ccgaaaagtg ccacctgacc gtaactataa cggtcctaag gtagcgaaag ctcagatctc 660
ccgatcccct atggtgcact ctcagtacaa tctgctctga tgccgcatag ttaagccagt 720
atctgctccc tgcttgtgtg ttggaggtcg ctgagtagtg cgcgagcaaa atttaagcta 780
caacaaggca aggcttgacc gacaattgca tgaagaatct gcttagggtt aggcgttttg 840
cgctgcttcg cgatgtacgg gccagatata cgcgttgaat tcatctatgt cgggtgcgga 900
gaaagaggta atgaaatggc attatgggta ttatgggtct gcattaatga atcggccaga 960
tatcgacata tgctggccac cgtacatgtg gcttcccatg ctcgcaagcc ctggcccgag 1020
ttcgagcaca atgtcatgac caggtgcaat atgcatctgg ggtcccggcg atcgcccgag 1080
gcatgttcat gccctaccag tgcaacatgc aatttgtgaa ggtgctgctg gagcccgatg 1140
ccatgtccag agtgagcctg acgggggtgt ttgacatgaa tgtggagctg tggaaaattc 1200
tgagatatga tgaatccaag accaggtgcc gggcctgcga atgcggaggc aagcacgcca 1260
ggcttcagcc cgtgtgtgtg gaggtgacgg aggacctgcg acccgatcat ttggtgttgt 1320
cctgcaacgg gacggagttc ggctccagcg gggaagaatc tgactagagt gagtagtgtt 1380
tgggggtggg tgggagcctg catgatgggc agaatgacta aaatctgtgt ttttctgtgt 1440
gttgcagcag catgagcgga agcgcctcct ttgagggagg ggtattcagc ccttatctga 1500
cggggcgtct cccctcctgg gcgggagtgc gtcagaatgt gatgggatcc acggtggacg 1560
gccggcccgt gcagcccgcg aactcttcaa ccctgaccta cgcgaccctg agctcctcgt 1620
ccgtggacgc agctgccgcc gcagctgctg cttccgccgc cagcgccgtg cgcggaatgg 1680
ccctgggcgc cggctactac agctctctgg tggccaactc gagttccacc aataatcccg 1740
ccagcctgaa cgaggagaag ctgttgctgc tgatggccca gctcgaggcc ctgacccagc 1800
gcctgggcga gctgacccag caggtggctc agctgcaggc ggagacgcgg gccgcggttg 1860
ccacggtgaa aaccaaataa aaaatgaatc aataaataaa cggagacggt tgttgatttt 1920
aacacagagt cttgaatctt tatttgattt ttcgcgcgcg gtaggccctg gaccaccggt 1980
ctcgatcatt gagcacccgg tggatctttt ccaggacccg gtagaggtgg gcttggatgt 2040
tgaggtacat gggcatgagc ccgtcccggg ggtggaggta gctccattgc agggcctcgt 2100
gctcgggggt ggtgttgtaa atcacccagt catagcaggg gcgcagggcg tggtgctgca 2160
cgatgtcttt gaggaggaga ctgatggcca cgggcagccc cttggtgtag gtgttgacga 2220
acctattgag ctgggaggga tgcatgcggg gggagatgag atgcatcttg gcctggatct 2280
tgagattggc gatgttcccg cccagatccc gccgggggtt catgttgtgc aggaccacca 2340
gcacggtgta tccggtgcac ttggggaatt tgtcatgcaa cttggaaggg aaggcgtgaa 2400
agaatttgga gacgcccttg tgaccgccca ggttttccat gcactcatcc atgatgatgg 2460
cgatgggccc gtgggcggcg gcctgggcaa agacgtttcg ggggtcggac acatcgtagt 2520
tgtggtcctg ggtgagctcg tcataggcca ttttaatgaa tttggggcgg agggtacccg 2580
actgggggac aaaggtgccc tcgatcccgg gggcgtagtt cccctcgcag atctgcatct 2640
cccaggcctt gagctcggag ggggggatca tgtccacctg cggggcgatg aaaaaaacgg 2700
tttccggggc gggggagatg agctgcgccg aaagcaggtt ccggagcagc tgggacttgc 2760
cgcagccggt ggggccgtag atgaccccga tgaccggctg caggtggtag ttgagggaga 2820
gacagctgcc gtcctcgcgg aggagggggg ccacctcgtt catcatctcg cgcacatgca 2880
tgttctcgcg cacgagttcc gccaggaggc gctcgccccc cagcgagagg agctcttgca 2940
gcgaggcgaa gtttttcagc ggcttgagcc cgtcggccat gggcattttg gagagggtct 3000
gttgcaagag ttccagacgg tcccagagct cggtgatgtg ctctagggca tctcgatcca 3060
gcagacctcc tcgtttcgcg ggttggggcg actgcgggag tagggcacca ggcgatgggc 3120
gtccagcgag gccagggtcc ggtccttcca gggtcgcagg gtccgcgtca gcgtggtctc 3180
cgtcacggtg aaggggtgcg cgccgggctg ggcgcttgcg agggtgcgct tcaggctcat 3240
ccggctggtc gagaaccgct cccggtcggc gccctgcgcg tcggccaggt agcaattgag 3300
catgagttcg tagttgagcg cctcggccgc gtggcccttg gcgcggagct tacctttgga 3360
agtgtgtccg cagacgggac agaggaggga cttgagggcg tagagcttgg gggcgaggaa 3420
gacggactcg ggggcgtagg cgtccgcgcc gcagctggcg cagacggtct cgcactccac 3480
gagccaggtg aggtcggggc ggtcggggtc aaaaacgagg tttcctccgt gctttttgat 3540
gcgtttctta cctctggtct ccatgagctc gtgtccccgc tgggtgacaa agaggctgtc 3600
cgtgtccccg tagaccgact ttatgggccg gtcctcgagc ggggtgccgc ggtcctcgtc 3660
gtagaggaac cccgcccact ccgagacgaa ggcccgggtc caggccagca cgaaggaggc 3720
cacgtgggag gggtagcggt cgttgtccac cagcgggtcc accttctcca gggtatgcaa 3780
gcacatgtcc ccctcgtcca catccaggaa ggtgattggc ttgtaagtgt aggccacgtg 3840
accgggggtc ccggccgggg gggtataaaa gggggcgggc ccctgctcgt cctcactgtc 3900
ttccggatcg ctgtccagga gcgccagctg ttggggtagg tattccctct cgaaggcggg 3960
catgacctcg gcactcaggt tgtcagtttc tagaaacgag gaggatttga tattgacggt 4020
gccgttggag acgcctttca tgagcccctc gtccatctgg tcagaaaaga cgatcttttt 4080
gttgtcgagc ttggtggcga aggagccgta gagggcgttg gagagcagct tggcgatgga 4140
gcgcatggtc tggttctttt ccttgtcggc gcgctccttg gcggcgatgt tgagctgcac 4200
gtactcgcgc gccacgcact tccattcggg gaagacggtg gtgagctcgt cgggcacgat 4260
tctgacccgc cagccgcggt tgtgcagggt gatgaggtcc acgctggtgg ccacctcgcc 4320
gcgcaggggc tcgttggtcc agcagaggcg cccgcccttg cgcgagcaga aggggggcag 4380
cgggtccagc atgagctcgt cgggggggtc ggcgtccacg gtgaagatgc cgggcaggag 4440
ctcggggtcg aagtagctga tgcaggtgcc cagatcgtcc agacttgctt gccagtcgcg 4500
cacggccagc gcgcgctcgt aggggctgag gggcgtgccc cagggcatgg ggtgcgtgag 4560
cgcggaggcg tacatgccgc agatgtcgta gacgtagagg ggctcctgga ggacgccgat 4620
gtaggtgggg tagcagcgcc ccccgcggat gctggcgcgc acgtagtcgt acagctcgtg 4680
cgagggcgcg aggagccccg tgccgagatt ggagcgctgc ggcttttcgg cgcggtagac 4740
gatctggcgg aagatggcgt gggagttgga ggagatggtg ggcctctgga agatgttgaa 4800
gtgggcatgg ggcagtccga ccgagtccct gatgaagtgg gcgtaggagt cctgcagctt 4860
ggcgacgagc tcggcggtga cgaggacgtc cagggcgcag tagtcgaggg tctcttggat 4920
gatgtcgtac ttgagctggc ccttctgctt ccacagctcg cggttgagaa ggaactcttc 4980
gcggtccttc cagtactctt cgagggggaa cccgtcctga tcggcacggt aagagcccac 5040
catgtagaac tggttgacgg ccttgtaggc gcagcagccc ttctccacgg ggagggcgta 5100
agcttgcgcg gccttgcgca gggaggtgtg ggtgagggcg aaggtgtcgc gcaccatgac 5160
tttgaggaac tggtgcttga agtcgaggtc gtcgcagccg ccctgctccc agagctggaa 5220
gtccgtgcgc ttcttgtagg cggggttggg caaagcgaaa gtaacatcgt tgaagaggat 5280
cttgcccgcg cggggcatga agttgcgagt gatgcggaaa ggctggggca cctcggcccg 5340
gttgttgatg acctgggcgg cgaggacgat ctcgtcgaag ccgttgatgt tgtgcccgac 5400
gatgtagagt tccacgaatc gcgggcggcc cttgacgtgg ggcagcttct tgagctcgtc 5460
gtaggtgagc tcggcggggt cgctgagccc gtgctgctcg agggcccagt cggcgacgtg 5520
ggggttggcg ctgaggaagg aagtccagag atccacggcc agggcggtct gcaagcggtc 5580
ccggtactga cggaactgct ggcccacggc cattttttcg ggggtgacgc agtagaaggt 5640
gcgggggtcg ccgtgccagc ggtcccactt gagctggagg gcgaggtcgt gggcgagctc 5700
gacgagcggc gggtccccgg agagtttcat gaccagcatg aaggggacga gctgcttgcc 5760
gaaggacccc atccaggtgt aggtttccac atcgtaggtg aggaagagcc tttcggtgcg 5820
aggatgcgag ccgatgggga agaactggat ctcctgccac cagttggagg aatggctgtt 5880
gatgtgatgg aagtagaaat gccgacggcg cgccgagcac tcgtgcttgt gtttatacaa 5940
gcgtccgcag tgctcgcaac gctgcacggg atgcacgtgc tgcacgagct gtacctgggt 6000
tcctttgacg aggaatttca gtgggcagtg gagcgctggc ggctgcatct ggtgctgtac 6060
tacgtcctgg ccatcggcgt ggccatcgtc tgcctcgatg gtggtcatgc tgacgagccc 6120
gcgcgggagg caggtccaga cctcggctcg gacgggtcgg agagcgagga cgagggcgcg 6180
caggccggag ctgtccaggg tcctgagacg ctgcggagtc aggtcagtgg gcagcggcgg 6240
cgcgcggttg acttgcagga gcttttccag ggcgcgcggg aggtccagat ggtacttgat 6300
ctccacggcg ccgttggtgg cgacgtccac ggcttgcagg gtcccgtgcc cctggggcgc 6360
caccaccgtg ccccgtttct tcttgggcgg cggcggctcc atgcttagaa gcggcggcga 6420
ggacgcgcgc cgggcggcag gggcggctcg gggcccggag gcaggggcgg caggggcacg 6480
tcggcgccgc gcgcgggcag gttctggtac tgcgcccgga gaagactggc gtgagcgacg 6540
acgcgacggt tgacgtcctg gatctgacgc ctctgggtga aggccacggg acccgtgagt 6600
ttgaacctga aagagagttc gacagaatca atctcggtat cgttgacggc ggcctgccgc 6660
aggatctctt gcacgtcgcc cgagttgtcc tggtaggcga tctcggtcat gaactgctcg 6720
atctcctcct cctgaaggtc tccgcggccg gcgcgctcga cggtggccgc gaggtcgttg 6780
gagatgcggc ccatgagctg cgagaaggcg ttcatgccgg cctcgttcca gacgcggctg 6840
tagaccacgg ctccgtcggg gtcgcgcgcg cgcatgacca cctgggcgag gttgagctcg 6900
acgtggcgcg tgaagaccgc gtagttgcag aggcgctggt agaggtagtt gagcgtggtg 6960
gcgatgtgct cggtgacgaa gaagtacatg atccagcggc ggagcggcat ctcgctgacg 7020
tcgcccaggg cttccaagcg ctccatggcc tcgtagaagt ccacggcgaa gttgaaaaac 7080
tgggagttgc gcgccgagac ggtcaactcc tcctccagaa gacggatgag ctcggcgatg 7140
gtggcgcgca cctcgcgctc gaaggccccg gggggctcct cttccatttc ctcctcttcc 7200
tcctccacta acatctcttc tacttcctcc tcaggaggcg gcggcggggg aggggccctg 7260
cgtcgccggc ggcgcacggg cagacggtcg atgaagcgct cgatggtctc cccgcgccgg 7320
cgacgcatgg tctcggtgac ggcgcgcccg tcctcgcggg gccgcagcgt gaagacgccg 7380
ccgcgcatct ccaggtggcc gccggggggg tctccgttgg gcagggagag ggcgctgacg 7440
atgcatctta tcaattgacc cgtagggact ccgcgcaagg acctgagcgt ctcgagatcc 7500
acgggatccg aaaaccgctg aacgaaggct tcgagccagt cgcagtcgca aggtaggctg 7560
agcccggttt cttgttcttc gggtatttgg tcgggaggcg ggcgggcgat gctgctggtg 7620
atgaagttga agtaggcggt cctgagacgg cggatggtgg cgaggagcac caggtccttg 7680
ggcccggctt gctggatgcg cagacggtcg gccatgcccc aggcgtggtc ctgacacctg 7740
gcgaggtcct tgtagtagtc ctgcatgagc cgctccacgg gcacctcctc ctcgcccgcg 7800
cggccgtgca tgcgcgtgag cccgaacccg cgctgcggct ggacgagcgc caggtcggcg 7860
acgacgcgct cggcgaggat ggcctgctgg atctgggtga gggtggtctg gaagtcgtcg 7920
aagtcgacga agcggtggta ggctccggtg ttgatggtgt aggagcagtt ggccatgacg 7980
gaccagttga cggtctggtg gccggggcgc acgagctcgt ggtacttgag gcgcgagtag 8040
gcgcgcgtgt cgaagatgta gtcgttgcag gtgcgcacga ggtactggta tccgacgagg 8100
aagtgcggcg gcggctggcg gtagagcggc catcgctcgg tggcgggggc gccgggcgcg 8160
aggtcctcga gcatgaggcg gtggtagccg tagatgtacc tggacatcca ggtgatgccg 8220
gcggcggtgg tggaggcgcg cgggaactcg cggacgcggt tccagatgtt gcgcagcggc 8280
aggaagtagt tcatggtggc cgcggtctgg cccgtgaggc gcgcgcagtc gtggatgctc 8340
tagacatacg ggcaaaaacg aaagcggtca gcggctcgac tccgtggcct ggaggctaag 8400
cgaacgggtt gggctgcgcg tgtaccccgg ttcgaatctc gaatcaggct ggagccgcag 8460
ctaacgtggt actggcactc ccgtctcgac ccaagcctgc taacgaaacc tccaggatac 8520
ggaggcgggt cgttttttgg ccttggtcgc tggtcatgaa aaactagtaa gcgcggaaag 8580
cggccgcccg cgatggctcg ctgccgtagt ctggagaaag aatcgccagg gttgcgttgc 8640
ggtgtgcccc ggttcgagcc tcagcgctcg gcgccggccg gattccgcgg ctaacgtggg 8700
cgtggctgcc ccgtcgtttc caagacccct tagccagccg acttctccag ttacggagcg 8760
agcccctctt tttttcttgt gtttttgcca gatgcatccc gtactgcggc agatgcgccc 8820
ccaccctcca ccacaaccgc ccctaccgca gcagcagcaa cagccggcgc ttctgccccc 8880
gccccagcag cagcagccag ccactaccgc ggcggccgcc gtgagcggag ccggcgttca 8940
gtatgacctg gccttggaag agggcgaggg gctggcgcgg ctgggggcgt cgtcgccgga 9000
gcggcacccg cgcgtgcaga tgaaaaggga cgctcgcgag gcctacgtgc ccaagcagaa 9060
cctgttcaga gacaggagcg gcgaggagcc cgaggagatg cgcgcctccc gcttccacgc 9120
ggggcgggag ctgcggcgcg gcctggaccg aaagcgggtg ctgagggacg aggatttcga 9180
ggcggacgag ctgacgggga tcagccccgc gcgcgcgcac gtggccgcgg ccaacctggt 9240
cacggcgtac gagcagaccg tgaaggagga gagcaacttc caaaaatcct tcaacaacca 9300
cgtgcgcacg ctgatcgcgc gcgaggaggt gaccctgggc ctgatgcacc tgtgggacct 9360
gctggaggcc atcgtgcaga accccacgag caagccgctg acggcgcagc tgtttctggt 9420
ggtgcagcac agtcgggaca acgagacgtt cagggaggcg ctgctgaata tcaccgagcc 9480
cgagggccgc tggctcctgg acctggtgaa cattctgcag agcatcgtgg tgcaggagcg 9540
cgggctgccg ctgtccgaga agctggcggc catcaacttc tcggtgctga gcctgggcaa 9600
gtactacgct aggaagatct acaagacccc gtacgtgccc atagacaagg aggtgaagat 9660
cgatgggttt tacatgcgca tgaccctgaa agtgctgacc ctgagcgacg atctgggggt 9720
gtaccgcaac gacaggatgc accgcgcggt gagcgccagc cgccggcgcg agctgagcga 9780
ccaggagctg atgcacagcc tgcagcgggc cctgaccggg gccgggaccg agggggagag 9840
ctactttgac atgggcgcgg acctgcgctg gcagcccagc cgccgggcct tggaagctgc 9900
cggcggcgtg ccctacgtgg aggaggtgga cgatgaggag gaggagggcg agtacctgga 9960
agactgatgg cgcgaccgta tttttgctag atgcagcaac agccaccgcc gccgcctcct 10020
gatcccgcga tgcgggcggc gctgcagagc cagccgtccg gcattaactc ctcggacgat 10080
tggacccagg ccatgcaacg catcatggcg ctgacgaccc gcaatcccga agcctttaga 10140
cagcagcctc aggccaaccg gctctcggcc atcctggagg ccgtggtgcc ctcgcgctcg 10200
aaccccacgc acgagaaggt gctggccatc gtgaacgcgc tggtggagaa caaggccatc 10260
cgcggcgacg aggccgggct ggtgtacaac gcgctgctgg agcgcgtggc ccgctacaac 10320
agcaccaacg tgcagacgaa cctggaccgc atggtgaccg acgtgcgcga ggcggtgtcg 10380
cagcgcgagc ggttccaccg cgagtcgaac ctgggctcca tggtggcgct gaacgccttc 10440
ctgagcacgc agcccgccaa cgtgccccgg ggccaggagg actacaccaa cttcatcagc 10500
gcgctgcggc tgatggtggc cgaggtgccc cagagcgagg tgtaccagtc ggggccggac 10560
tacttcttcc agaccagtcg ccagggcttg cagaccgtga acctgagcca ggctttcaag 10620
aacttgcagg gactgtgggg cgtgcaggcc ccggtcgggg accgcgcgac ggtgtcgagc 10680
ctgctgacgc cgaactcgcg cctgctgctg ctgctggtgg cgcccttcac ggacagcggc 10740
agcgtgagcc gcgactcgta cctgggctac ctgcttaacc tgtaccgcga ggccatcggg 10800
caggcgcacg tggacgagca gacctaccag gagatcaccc acgtgagccg cgcgctgggc 10860
caggaggacc cgggcaacct ggaggccacc ctgaacttcc tgctgaccaa ccggtcgcag 10920
aagatcccgc cccagtacgc gctgagcacc gaggaggagc gcatcctgcg ctacgtgcag 10980
cagagcgtgg ggctgttctt gatgcaggag ggggccacgc ccagcgccgc gctcgacatg 11040
accgcgcgca acatggagcc cagcatgtac gcccgcaacc gcccgttcat caataagctg 11100
atggactact tgcatcgggc ggccgccatg aactcggact actttaccaa cgccatcttg 11160
aacccgcact ggctcccgcc gcccgggttc tacacgggcg agtacgacat gcccgacccc 11220
aacgacgggt tcctgtggga cgacgtggac agcagcgtgt tctcgccgcg gcccaccacc 11280
accaccgtgt ggaagaaaga gggcggggac cggcggccgt cctcggcgct gtccggtcgc 11340
gcgggtgctg ccgcggcggt gcccgaggct gccagcccct tcccgagcct gcccttttcg 11400
ctgaacagcg tgcgcagcag cgagctgggt cggctgacgc ggccgcgcct gctgggcgag 11460
gaggagtacc tgaacgactc cttgttgaag cccgagcgcg agaagaactt ccccaataac 11520
gggatagaga gcctggtgga caagatgagc cgctggaaga cgtacgcgca cgagcacagg 11580
gacgagcccc gagctagcag cgcaggcacc cgtagacgcc agcggcacga caggcagcgg 11640
ggactggtgt gggacgatga ggattccgcc gacgacagca gcgtgttgga cttgggtggg 11700
agtggtggtg gtaacccgtt cgctcacctg cgcccccgta tcgggcgcct gatgtaagaa 11760
tctgaaaaaa taaaagacgg tactcaccaa ggccatggcg accagcgtgc gttcttctct 11820
gttgtttgta gtagtatgat gaggcgcgtg tacccggagg gtcctcctcc ctcgtacgag 11880
agcgtgatgc agcaggcggt ggcggcggcg atgcagcccc cgctggaggc gccttacgtg 11940
cccccgcggt acctggcgcc tacggagggg cggaacagca ttcgttactc ggagctggca 12000
cccttgtacg ataccacccg gttgtacctg gtggacaaca agtcggcgga catcgcctcg 12060
ctgaactacc agaacgacca cagcaacttc ctgaccaccg tggtgcagaa caacgatttc 12120
acccccacgg aggccagcac ccagaccatc aactttgacg agcgctcgcg gtggggcggc 12180
cagctgaaaa ccatcatgca caccaacatg cccaacgtga acgagttcat gtacagcaac 12240
aagttcaagg cgcgggtgat ggtctcgcgc aagaccccca acggggtcac ggtaggggat 12300
gattatgatg gtagtcagga cgagctgacc tacgagtggg tggagtttga gctgcccgag 12360
ggcaacttct cggtgaccat gaccatcgat ctgatgaaca acgccatcat cgacaactac 12420
ttggcggtgg ggcggcagaa cggggtgctg gagagcgaca tcggcgtgaa gttcgacacg 12480
cgcaacttcc ggctgggctg ggaccccgtg accgagctgg tgatgccggg cgtgtacacc 12540
aacgaggcct tccaccccga catcgtcctg ctgcccggct gcggcgtgga cttcaccgag 12600
agccgcctca gcaacctgct gggcatccgc aagcggcagc ccttccagga gggcttccag 12660
atcctgtacg aggacctgga ggggggcaac atccccgcgc tcttggatgt cgaagcctat 12720
gaagaaagta aggaaaaagc agaggctgag gcaactacag ccgtggctac cgccgcgact 12780
gtggcagatg ccactgtcac caggggcgat acattcgcca cccaggcgga ggaagcagcc 12840
gccctagcgg cgaccgatga tagtgaaagt aagatagtca tcaagccggt ggagaaggac 12900
agcaagaaca ggagctacaa cgttctaccg gatggaaaga acaccgccta ccgcagctgg 12960
tacctggcct acaactacgg cgaccccgag aagggcgtgc gctcctggac gctgctcacc 13020
acctcggacg tcacctgcgg cgtggagcaa gtctactggt cgctgcccga catgatgcaa 13080
gacccggtca ccttccgctc cacgcgacaa gttagcaact acccggtggt gggcgccgag 13140
ctcctgcccg tctactccaa gagcttcttc aacgagcagg ccgtctactc gcagcagctg 13200
cgtgccttca cctcgctcac gcacgtcttc aaccgcttcc ccgagaacca gatcctcgtc 13260
cgcccgcccg cgcccaccat taccaccgtc agtgaaaacg ttcctgctct cacagatcac 13320
gggaccctgc cgctgcgcag cagtatccgg ggagtccagc gcgtgaccgt cactgacgcc 13380
agacgccgca cctgccccta cgtctacaag gccctgggcg tagtcgcgcc gcgcgtcctc 13440
tcgagccgca ccttctaaaa aatgtccatt ctcatctcgc ccagtaataa caccggttgg 13500
ggcctgcgcg cgcccagcaa gatgtacgga ggcgctcgcc aacgctccac gcaacacccc 13560
gtgcgcgtgc gcgggcactt ccgcgctccc tggggcgccc tcaagggccg cgtgcgctcg 13620
cgcaccaccg tcgacgacgt gatcgaccag gtggtggccg acgcgcgcaa ctacacgccc 13680
gccgccgcgc ccgcctccac cgtggacgcc gtcatcgaca gcgtggtggc cgacgcgcgc 13740
cggtacgccc gcgccaagag ccggcggcgg cgcatcgccc ggcggcaccg gagcaccccc 13800
gccatgcgcg cggcgcgagc cttgctgcgc agggccaggc gcacgggacg cagggccatg 13860
ctcagggcgg ccagacgcgc ggcctccggc agcagcagcg ccggcaggac ccgcagacgc 13920
gcggccacgg cggcggcggc ggccatcgcc agcatgtccc gcccgcggcg cggcaacgtg 13980
tactgggtgc gcgacgccgc caccggtgtg cgcgtgcccg tgcgcacccg cccccctcgc 14040
acttgaagat gctgacttcg cgatgttgat gtgtcccagc ggcgaggagg atgtccaagc 14100
gcaaatacaa ggaagagatg ctccaggtca tcgcgcctga gatctacggc cccgcggcgg 14160
cggtgaagga ggaaagaaag ccccgcaaac tgaagcgggt caaaaaggac aaaaaggagg 14220
aggaagatga cggactggtg gagtttgtgc gcgagttcgc cccccggcgg cgcgtgcagt 14280
ggcgcgggcg gaaagtgaaa ccggtgctgc ggcccggcac cacggtggtc ttcacgcccg 14340
gcgagcgttc cggctccgcc tccaagcgct cctacgacga ggtgtacggg gacgaggaca 14400
tcctcgagca ggcggtcgag cgtctgggcg agtttgctta cggcaagcgc agccgccccg 14460
cgcccttgaa agaggaggcg gtgtccatcc cgctggacca cggcaacccc acgccgagcc 14520
tgaagccggt gaccctgcag caggtgctgc cgagcgcggc gccgcgccgg ggcttcaagc 14580
gcgagggcgg cgaggatctg tacccgacca tgcagctgat ggtgcccaag cgccagaagc 14640
tggaggacgt gctggagcac atgaaggtgg accccgaggt gcagcccgag gtcaaggtgc 14700
ggcccatcaa gcaggtggcc ccgggcctgg gcgtgcagac cgtggacatc aagatcccca 14760
cggagcccat ggaaacgcag accgagcccg tgaagcccag caccagcacc atggaggtgc 14820
agacggatcc ctggatgcca gcggcttcca ccaccaccac tcgccgaaga cgcaagtacg 14880
gcgcggccag cctgctgatg cccaactacg cgctgcatcc ttccatcatc cccacgccgg 14940
gctaccgcgg cacgcgcttc taccgcggct acaccagcag ccgccgccgc aagaccacca 15000
cccgccgccg tcgtcgcagc cgccgcagca gcaccgcgac ttccgccttg gtgcggagag 15060
tgtatcgcag cgggcgcgag cctctgaccc tgccgcgcgc gcgctaccac ccgagcatcg 15120
ccatttaact accgcctcct acttgcagat atggccctca catgccgcct ccgcgtcccc 15180
attacgggct accgaggaag aaagccgcgc cgtagaaggc tgacggggaa cgggctgcgt 15240
cgccatcacc accggcggcg gcgcgccatc agcaagcggt tggggggagg cttcctgccc 15300
gcgctgatcc ccatcatcgc cgcggcgatc ggggcgatcc ccggcatagc ttccgtggcg 15360
gtgcaggcct ctcagcgcca ctgagacaca aaaaagcatg gatttgtaat aaaaaaatgg 15420
actgacgctc ctggtcctgt gatgtgtgtt tttagatgga agacatcaat ttttcgtccc 15480
tggcaccgcg acacggcacg cggccgttta tgggcacctg gagcgacatc ggcaacagcc 15540
aactgaacgg gggcgccttc aattggagca gtctctggag cgggcttaag aatttcgggt 15600
ccacgctcaa aacctatggc aacaaggcgt ggaacagcag cacagggcag gcgctgaggg 15660
aaaagctgaa agagcagaac ttccagcaga aggtggtcga tggcctggcc tcgggcatca 15720
acggggtggt ggacctggcc aaccaggccg tgcagaaaca gatcaacagc cgcctggacg 15780
cggtcccgcc cgcggggtcc gtggagatgc cccaggtgga ggaggagctg cctcccctgg 15840
acaagcgcgg cgacaagcga ccgcgtcccg acgcggagga gacgctgctg acgcacacgg 15900
acgagccgcc cccgtacgag gaggcggtga aactgggtct gcccaccacg cggcccgtgg 15960
cgcctctggc caccggggtg ctgaaaccca gcagcagcag ccagcccgcg accctggact 16020
tgcctccgcc tgcttcccgc ccctccacag tggctaagcc cctgccgccg gtggccgtcg 16080
cgtcgcgcgc cccccgaggc cgcccccagg cgaactggca gagcactctg aacagcatcg 16140
tgggtctggg agtgcagagt gtgaagcgcc gccgctgcta ttaaaagaca ctgtagcgct 16200
taacttgctt gtctgtgtgt gtatatgtat gtccgccgac cagaaggagg aagaggcgcg 16260
tcgccgagtt gcaagatggc caccccatcg atgctgcccc agtgggcgta catgcacatc 16320
gccggacagg acgcttcgga gtacctgagt ccgggtctgg tgcagttcgc ccgcgccaca 16380
gacacctact tcagtctggg gaacaagttt aggaacccca cggtggcgcc cacgcacgat 16440
gtgaccaccg accgcagcca gcggctgacg ctgcgcttcg tgcccgtgga ccgcgaggac 16500
aacacctact cgtacaaagt gcgctacacg ctggccgtgg gcgacaaccg cgtgctggac 16560
atggccagca cctactttga catccgcggc gtgctggatc ggggccccag cttcaaaccc 16620
tactccggca ccgcctacaa cagcctagct cccaagggag cgcccaacac ctcacagtgg 16680
aaggattccg acagcaaaat gcatactttt ggagttgctg ccatgcccgg tgttgttggt 16740
aaaaaaatag aagccgatgg tctgcctatt ggaatagatt catcctctgg aactgacacc 16800
ataatttatg ctgataaaac tttccaacca gagccacagg ttggaagtga cagttgggtc 16860
gacaccaatg gtgcagagga aaaatatgga ggtagagctc ttaaggacac tacaaacatg 16920
aagccctgct acggttcttt tgccaggcct accaacaaag aaggtggaca ggctaacata 16980
aaagattctg aaactgccag cactactcct aactatgata tagatttggc attctttgac 17040
agcaaaaata ttgcagctaa ctacgatcca gatattgtaa tgtacacaga aaatgttgag 17100
ttgcaaactc cagatactca tattgtgttt aagccaggaa cttcagatga aagttcagaa 17160
gccaatttgg gccagcaggc catgcccaac agacccaact acatcgggtt cagagacaac 17220
tttatcgggc tcatgtacta caacagcact ggcaatatgg gtgtactggc tggtcaggcc 17280
tcccagctaa atgctgtggt ggacttgcag gacagaaaca ccgaactgtc ctaccagctc 17340
ttgcttgact ctctgggtga cagaaccagg tatttcagta tgtggaatca ggcggtggac 17400
agctatgacc ccgatgtgcg cattattgaa aatcacggtg tggaggatga actccccaat 17460
tattgcttcc ctttgaatgg tgtaggcttt acagatactt accagggtgt taaagttaag 17520
acagatacag ccgctactgg taccaatgga acgcagtggg acaaagatga taccacagtc 17580
agcactgcca atgagatcca ctcaggcaat cctttcgcca tggagatcaa catccaggcc 17640
aacctgtggc ggaacttcct ctacgcgaac gtggcgctgt acctgcccga ctcctacaag 17700
tacacgccgg ccaacatcac gctgccgacc aacaccaaca cctacgatta catgaacggc 17760
cgcgtggtgg cgccctcgct ggtggacgcc tacatcaaca tcggggcgcg ctggtcgctg 17820
gaccccatgg acaacgtcaa ccccttcaac caccaccgca acgcgggcct gcgctaccgc 17880
tccatgctcc tgggcaacgg gcgctacgtg cccttccaca tccaggtgcc ccaaaagttt 17940
ttcgccatca agagcctcct gctcctgccc gggtcctaca cctacgagtg gaacttccgc 18000
aaggacgtca acatgatcct gcagagctcc ctcggcaacg acctgcgcac ggacggggcc 18060
tccatcgcct tcaccagcat caacctctac gccaccttct tccccatggc gcacaacacc 18120
gcctccacgc tcgaggccat gctgcgcaac gacaccaacg accagtcctt caacgactac 18180
ctctcggcgg ccaacatgct ctaccccatc ccggccaacg ccaccaacgt gcccatctcc 18240
atcccctcgc gcaactgggc cgccttccgc ggatggtcct tcacgcgcct caagacccgc 18300
gagacgccct cgctcggctc cgggttcgac ccctacttcg tctactcggg ctccatcccc 18360
tacctcgacg gcaccttcta cctcaaccac accttcaaga aggtctccat caccttcgac 18420
tcctccgtca gctggcccgg caacgaccgc ctcctgacgc ccaacgagtt cgaaatcaag 18480
cgcaccgtcg acggagaggg atacaacgtg gcccagtgca acatgaccaa ggactggttc 18540
ctggtccaga tgctggccca ctacaacatc ggctaccagg gcttctacgt gcccgagggc 18600
tacaaggacc gcatgtactc cttcttccgc aacttccagc ccatgagccg ccaggtcgtg 18660
gacgaggtca actacaagga ctaccaggcc gtcaccctgg cctaccagca caacaactcg 18720
ggcttcgtcg gctacctcgc gcccaccatg cgccagggcc agccctaccc cgccaactac 18780
ccctacccgc tcatcggcaa gagcgccgtc gccagcgtca cccagaaaaa gttcctctgc 18840
gaccgggtca tgtggcgcat ccccttctcc agcaacttca tgtccatggg cgcgctcacc 18900
gacctcggcc agaacatgct ctacgccaac tccgcccacg cgctagacat gaatttcgaa 18960
gtcgacccca tggatgagtc cacccttctc tatgttgtct tcgaagtctt cgacgtcgtc 19020
cgagtgcacc agccccaccg cggcgtcatc gaggccgtct acctgcgcac gcccttctcg 19080
gccggcaacg ccaccaccta aagccccgct cttgcttctt gcaagatgac ggcctgtggc 19140
tccggcgagc aggagctcag ggccatcctc cgcgacctgg gctgcgggcc ctgcttcctg 19200
ggcaccttcg acaagcgctt cccgggattc atggccccgc acaagctggc ctgcgccatc 19260
gtcaacacgg ccggccgcga gaccgggggc gagcactggc tggccttcgc ctggaacccg 19320
cgctcccaca cctgctacct cttcgacccc ttcgggttct cggacgagcg cctcaagcag 19380
atctaccagt tcgagtacga gggcctgctg cgccgcagcg ccctggccac cgaggaccgc 19440
tgcatcaccc tggaaaagtc cacccagacc gtgcagggtc cgcgctcggc cgcctgcggg 19500
ctcttctgct gcatgttcct gcacgccttc gtgcactggc ccgaccgccc catggacaag 19560
aaccccacca tgaacttgct gacgggggtg cccaacggca tgctccagtc gccccaggtg 19620
gaacccaccc tgcgccgcaa ccaggaggcg ctctaccgct tcctcaacgc ccactccgcc 19680
tactttcgct cccaccgcgc gcgcatcgag aaggccaccg ccttcgaccg catgaatcaa 19740
gacatgtaaa ctgtgtgtat gtgaatgctt tattcatcat aataaacagc acatgtttat 19800
gccaccttct ctgaggctct gactttattt agaaatcgaa ggggttctgc cggctctcgg 19860
cgtgccccgc gggcagggat acgttgcgga actggtactt gggcagccac ttgaactcgg 19920
ggatcagcag cttcggcacg gggaggtcgg ggaacgagtc gctccacagc ttgcgcgtga 19980
gttgcagggc gcccagcagg tcgggcgcgg agatcttgaa atcgcagttg ggacccgcgt 20040
tctgcgcgcg agagttgcgg tacacggggt tgcagcactg gaacaccatc agggccgggt 20100
gcttcacgct cgccagcacc gtcgcgtcgg tgatgccctc cacgtccaga tcctcggcgt 20160
tggccatccc gaagggggtc atcttgcagg tctgccgccc catgctgggc acgcagccgg 20220
gcttgtggtt gcaatcgcag tgcaggggga tcagcatcat ctgagcctgc tcggagctca 20280
tgcccgggta catggccttc atgaaagcct ccagctggcg gaaggcctgc tgcgccttgc 20340
cgccctcggt gaagaagacc ccacaggact tgctagagaa ctggttggtg gcgcagcccg 20400
cgtcgtgcac gcagcagcgc gcgtcgttgt tggccagctg caccacgctg cgcccccagc 20460
ggttctgggt gatcttggcc cggtcggggt tctccttcag cgcgcgctgc ccgttctcgc 20520
tcgccacatc catctcgatc gtgtgctcct tctggatcat cacggtcccg tgcaggcacc 20580
gcagcttgcc ctcggcctcg gtgcacccgt gcagccacag cgcgcagccg gtgcactccc 20640
agttcttgtg ggcgatctgg gagtgcgagt gcacgaagcc ctgcaggaag cggcccatca 20700
tcgtggtcag ggtcttgttg ctggtgaagg tcagcgggat gccgcggtgc tcctcgttca 20760
catacaggtg gcagatgcgg cggtacacct cgccctgctc gggcatcagc tggaaggcgg 20820
acttcaggtc gctctccacg cggtaccgct ccatcagcag cgtcatcact tccatgccct 20880
tctcccaggc cgaaacgatc ggcaggctca gggggttctt caccgtcatc ttagtcgccg 20940
ccgccgaagt cagggggtcg ttctcgtcca gggtctcaaa cactcgcttg ccgtccttct 21000
cggtgatgcg cacgggggga aagctgaagc ccacggccgc cagctcctcc tcggcctgcc 21060
tttcgtcctc gctgtcctgg ctgatgtctt gcaaaggcac atgcttggtc ttgcggggtt 21120
tctttttggg cggcagaggc ggcggcggag acgtgctggg cgagcgcgag ttctcgctca 21180
ccacgactat ttcttcttct tggccgtcgt ccgagaccac gcggcggtag gcatgcctct 21240
tctggggcag aggcggaggc gacgggctct cgcggttcgg cgggcggctg gcagagcccc 21300
ttccgcgttc gggggtgcgc tcctggcggc gctgctctga ctgacttcct ccgcggccgg 21360
ccattgtgtt ctcctaggga gcaacaagca tggagactca gccatcgtcg ccaacatcgc 21420
catctgcccc cgccgccgac gagaaccagc agcagcagaa tgaaagctta accgccccgc 21480
cgcccagccc cacctccgac gccgccgcgg ccccagacat gcaagagatg gaggaatcca 21540
tcgagattga cctgggctac gtgacgcccg cggagcacga ggaggagctg gcagcgcgct 21600
tttcagcccc ggaagagaac caccaagagc agccagagca ggaagcagag agcgagcagc 21660
agcaggctgg gctcgagcat ggcgactacc tgagcggggc agaggacgtg ctcatcaagc 21720
atctggcccg ccaaagcatc atcgtcaagg acgcgctgct cgaccgcgcc gaggtgcccc 21780
tcagcgtggc ggagctcagc cgcgcctacg agcgcaacct cttctcgccg cgcgtgcccc 21840
ccaagcgcca gcccaacggc acctgcgagc ccaacccgcg cctcaacttc tacccggtct 21900
tcgcggtgcc cgaggccctg gccacctacc acctcttttt caagaaccaa aggatccccg 21960
tctcctgccg cgccaaccgc acccgcgccg acgccctgct caacctgggt cccggcgccc 22020
gcctacctga tatcacctcc ttggaagagg ttcccaagat cttcgagggt ctgggcagcg 22080
acgagactcg ggccgcgaac gctctgcaag gaagcggaga ggagcatgag caccacagcg 22140
ccctggtgga gttggaaggc gacaacgcgc gcctggcggt gctcaagcgc acggtcgagc 22200
tgacccactt cgcctacccg gcgctcaacc tgccccccaa ggtcatgagc gccgtcatgg 22260
accaggtgct catcaagcgc gcctcgcccc tctcagagga ggagatgcag gaccccgaga 22320
gctcggacga gggcaagccc gtggtcagcg acgagcagct ggcgcgctgg ctgggagcga 22380
gcagcacccc ccagagcctg gaagagcggc gcaagctcat gatggccgtg gtcctggtga 22440
ccgtggagct ggagtgtctg cgccgcttct tcgccgacgc ggagaccctg cgcaaggtcg 22500
aggagaacct gcactacctc ttcaggcacg ggttcgtgcg ccaggcctgc aagatctcca 22560
acgtggagct gaccaacctg gtctcctaca tgggcatcct gcacgagaac cgcctggggc 22620
agaacgtgct gcacaccacc ctgcgcgggg aggcccgccg cgactacatc cgcgactgcg 22680
tctacctgta cctctgccac acctggcaga cgggcatggg cgtgtggcag cagtgcctgg 22740
aggagcagaa cctgaaagag ctctgcaagc tcctgcagaa gaacctcaag gccctgtgga 22800
ccgggttcga cgagcgcacc accgcctcgg acctggccga cctcatcttc cccgagcgcc 22860
tgcggctgac gctgcgcaac gggctgcccg actttatgag ccaaagcatg ttgcaaaact 22920
ttcgctcttt catcctcgaa cgctccggga tcctgcccgc cacctgctcc gcactgccct 22980
cggacttcgt gccgctgacc ttccgcgagt gccccccgcc gctctggagc cactgctact 23040
tgctgcgcct ggccaactac ctggcctacc actcggacgt gatcgaggac gtcagcagcg 23100
agggtctgct cgagtgccac tgccgctgca acctctgcac gccgcaccgc tccttggcct 23160
gcaaccccca gctgctgagc gagacccaga tcatcggcac cttcgagttg caaggccccg 23220
gcgagggcaa ggggggtctc aaactcaccc cggggctgtg gacctcggcc tacttgcgca 23280
agttcgtgcc cgaggactac catcccttcg agatcaggtt ctacgaggac caatcccagc 23340
cgcccaaggc cgagctgtcg gcctgcgtca tcacccaggg ggccatcctg gcccaattgc 23400
aagccatcca gaaatcccgc caagaatttc tgctgaaaaa gggccacggg gtctacttgg 23460
acccccagac cggagaggag ctcaacccca gcttccccca ggatgccccg aggaagcagc 23520
aagaagctga aagtggagct gccgctgccg ccggaggatt tggaggaaga ctgggagagc 23580
agtcaggcag aggagatgga agactgggac agcactcagg cagaggagga cagcctgcaa 23640
gacagtctgg aggaggaaga cgaggtggag gaggaggcag aggaagaagc agccgccgcc 23700
agaccgtcgt cctcggcgga ggagaaagca agcagcacgg ataccatctc cgctccgggt 23760
cggggtcgcg gcggccgggc ccacagtaga tgggacgaga ccgggcgctt cccgaacccc 23820
accacccaga ccggtaagaa ggagcggcag ggatacaagt cctggcgggg gcacaaaaac 23880
gccatcgtct cctgcttgca agcctgcggg ggcaacatct ccttcacccg gcgctacctg 23940
ctcttccacc gcggggtgaa cttcccccgc aacatcttgc attactaccg tcacctccac 24000
agcccctact actgtttcca agaagaggca gaaacccagc agcagcagca gaaaaccagc 24060
ggcagcagca gcagctagaa aatccacagc ggcggcaggt ggactgagga tcgcggcgaa 24120
cgagccggcg cagacccggg agctgaggaa ccggatcttt cccaccctct atgccatctt 24180
ccagcagagt cgggggcagg agcaggaact gaaagtcaag aaccgttctc tgcgctcgct 24240
cacccgcagt tgtctgtatc acaagagcga agaccaactt cagcgcactc tcgaggacgc 24300
cgaggctctc ttcaacaagt actgcgcgct cactcttaaa gagtagcccg cgcccgccca 24360
cacacggaaa aaggcgggaa ttacgtcacc acctgcgccc ttcgcccgac catcatcatg 24420
agcaaagaga ttcccacgcc ttacatgtgg agctaccagc cccagatggg cctggccgcc 24480
ggcgccgccc aggactactc cacccgcatg aactggctca gtgccgggcc cgcgatgatc 24540
tcacgggtga atgacatccg cgcccaccga aaccagatac tcctagaaca gtcagcgatc 24600
accgccacgc cccgccatca ccttaatccg cgtaattggc ccgccgccct ggtgtaccag 24660
gaaattcccc agcccacgac cgtactactt ccgcgagacg cccaggccga agtccagctg 24720
actaactcag gtgtccagct ggccggcggc gccgccctgt gtcgtcaccg ccccgctcag 24780
ggtataaagc ggctggtgat ccgaggcaga ggcacacagc tcaacgacga ggtggtgagc 24840
tcttcgctgg gtctgcgacc tgacggagtc ttccaactcg ccggatcggg gagatcttcc 24900
ttcacgcctc gtcaggccgt cctgactttg gagagttcgt cctcgcagcc ccgctcgggc 24960
ggcatcggca ctctccagtt cgtggaggag ttcactccct cggtctactt caaccccttc 25020
tccggctccc ccggccacta cccggacgag ttcatcccga acttcgacgc catcagcgag 25080
tcggtggacg gctacgattg aatgtcccat ggtggcgcgg ctgacctagc tcggcttcga 25140
cacctggacc actgccgccg cttccgctgc ttcgctcggg atctcgccga gtttgcctac 25200
tttgagctgc ccgaggagca ccctcagggc ccggcccacg gagtgcggat cgtcgtcgaa 25260
gggggcctcg actcccacct gcttcggatt ttcagccagc gtccgatcct ggtcgagcgc 25320
gagcaaggac agacccttct gaccctgtac tgcatctgca accaccccgg cctgcatgaa 25380
agtctttgtt gtctgctgtg tactgagtat aataaaagct gagatcagcg actactccgg 25440
actcgattgt ggtgttcctg ctatcaaccg gtccctgttc ttcaccggga acgagaccga 25500
gctccagctc cagtgtaagc cccacaagaa gtatctcacc tggctgttcc agggctctcc 25560
gatcgccgtt gtcaaccact gcgacaacga cggagtcctg ctgagcggcc ctgccaacct 25620
tactttttcc acccgcagaa gcaagctcca gctcttccaa cccttcctcc ccgggaccta 25680
tcagtgcgtc tcgggaccct gccatcacac cttccacctg atcccgaata ccacagcgcc 25740
gctccccgct actaacaacc aaactaccca ccaacgccac cgtcgcgacc tttctgaatc 25800
taatactacc acccacaccg gaggtgagct ccgaggtcga ccaacctctg ggatttacta 25860
cggggttaac cccttaatta aggggattcc atatggtacg tacatcgcct ctcctacgag 25920
ctcctgcagc agcgccagaa gttcacctgc ctggtcggag tcaaccccat cgtcatcacc 25980
cagcagtcgg gcgataccaa ggggtgcatc cactgctcct gcgactcccc cgactgcgtc 26040
cacactctga tcaagaccct ctgcggcctc cgcgacctcc tccccatgaa ctaatcaccc 26100
ccttatccag tgaaataaag atcatattga tgatgatttt acagaaataa agatacaatc 26160
atattgatga tttgagttta ataaaaaata aagaatcact tacttgaaat ctgataccag 26220
gtctctgtcc atgttttctg ccaacaccac ttcactcccc tcttcccagc tctggtactg 26280
caggccccgg cgggctgcaa acttcctcca cacgctgaag gggatgtcaa attcctcctg 26340
tccctcaatc ttcattttat cttctatcag atgtccaaaa agcgcgtccg ggtggatgat 26400
gacttcgacc ccgtctaccc ctacgatgca gacaacgcac cgaccgtgcc cttcatcaac 26460
ccccccttcg tctcttcaga tggattccaa gagaagcccc tgggggtgct gtccctgcga 26520
ctggccgacc ccgtcaccac caagaacggg gaaatcaccc tcaagctggg agagggggtg 26580
gacctcgact cctcgggaaa actcatctcc aacacggcca ccaaggccgc cgcccctctc 26640
agtttttcca acaacaccat ttcccttaac atggatcacc ccttttacac taaagatgga 26700
aaattatcct tacaagtttc tccaccatta aatatactga gaacaagcat tctaaacaca 26760
ctagctttag gttttggatc aggtttagga ctccgtggct ctgccttggc agtacagtta 26820
gtctctccac ttacatttga tactgatgga aacataaagc ttaccttaga cagaggtttg 26880
catgttacaa caggagatgc aattgaaagc aacataagct gggctaaagg tttaaaattt 26940
gaagatggag ccatagcaac caacattgga aatgggttag agtttggaag cagtagtaca 27000
gaaacaggtg ttgatgatgc ttacccaatc caagttaaac ttggatctgg ccttagcttt 27060
gacagtacag gagccataat ggctggtaac aaagaagacg ataaactcac tttgtggaca 27120
acacctgatc catcgccaaa ctgtcaaata ctcgcagaaa atgatgcaaa actaacactt 27180
tgcttgacta aatgtggtag tcaaatactg gccactgtgt cagtcttagt tgtaggaagt 27240
ggaaacctaa accccattac tggcaccgta agcagtgctc aggtgtttct acgttttgat 27300
gcaaacggtg ttcttttaac agaacattct acactaaaaa aatactgggg gtataggcag 27360
ggagatagca tagatggcac tccatatacc aatgctgtag gattcatgcc caatttaaaa 27420
gcttatccaa agtcacaaag ttctactact aaaaataata tagtagggca agtatacatg 27480
aatggagatg tttcaaaacc tatgcttctc actataaccc tcaatggtac tgatgacagc 27540
aacagtacat attcaatgtc attttcatac acctggacta atggaagcta tgttggagca 27600
acatttgggg ctaactctta taccttctca tacatcgccc aagaatgaac actgtatccc 27660
accctgcatg ccaacccttc ccaccccact ctgtggaaaa aactctgaaa cacaaaataa 27720
aataaagttc aagtgtttta ttgattcaac agttttacag gattcgagca gttatttttc 27780
ctccaccctc ccaggacatg gaatacacca ccctctcccc ccgcacagcc ttgaacatct 27840
gaacgccatt ggtgatggac atgcttttgg tctccacgtt ccacacagtt tcagagcgag 27900
ccagtctcgg gtcggtcagg gagatgaaac cctccgggca caattgggag aagtactcgc 27960
ctattatctg gaagaagcag aagagcggcg gtgggaatca tagtccgcga acgggatcgg 28020
ccggtggtgt cgcatcaggc cccgcagcag tcgctgccgc cgccgctccg tcaagctgct 28080
gctcaggggg tccgggtcca gggactccct cagcatgatg cccacggccc tcagcatcag 28140
tcgtctggtg cggcgggcgc agcagcgcat gcggatctcg ctcaggtcgc tgcagtacgt 28200
gcaacacaga accaccaggt tgttcaacag tccatagttc aacacgctcc agccgaaact 28260
catcgcggga aggatgctac ccacgtggcc gtcgtaccag atcctcaggt aaatcaagtg 28320
gtgccccctc cagaacacgc tgcccacgta catgatctcc ttgggcatgt ggcggttcac 28380
cacctcccgg taccacatca ccctctggtt gaacatgcag ccccggatga tcctgcggaa 28440
ccacagggcc agcaccgccc cgcccgccat gcagcgaaga gaccccgggt cccggcaatg 28500
gcaatggagg acccaccgct cgtacccgtg gatcatctgg gagctgaaca agtctatgtt 28560
ggcacagcac aggcatatgc tcatgcatct cttcagcact ctcaactcct cgggggtcaa 28620
aaccatatcc cagggcacgg ggaactcttg caggacagcg aaccccgcag aacagggcaa 28680
tcctcgcaca gaacttacat tgtgcatgga cagggtatcg caatcaggca gcaccgggtg 28740
atcctccacc agagaagcgc gggtctcggt ctcctcacag cgtggtaagg gggccggccg 28800
atacgggtga tggcgggacg cggctgatcg tgttcgcgac cgtgtcatga tgcagttgct 28860
ttcggacata tttcctgaag tcttggcgcg ccaaagtcta gacagcgtcc atagcttacc 28920
gagcagcagc agcagcacac aacaggcgca agagtcagag aaaggctgag ctctaacctg 28980
tccacccgct ctctgctcaa tatatagccc agatctacac tgacgtaaag gccaaagtct 29040
aaaaataccc gccaaatagt cacacacgcc cagcacacgc ccagaaaccg gtgacacact 29100
caaaaaaata cgcgcacttc ctcaaacgcc caaactgccg tcatttccgg gttcccacgc 29160
tacgtcatca aaacacgact ttcaaattcc gtcgaccgtt aaaaacgtca cccgccccgc 29220
ccctaacggt cgcccgtctc tcagccaatc agcgccccgc atccccaaat tcaaacacct 29280
catttgcata ttaacgcgca ccaaaagttt gaggtatatt attgatgatg attt 29334
<210> 5
<211> 2890
<212> DNA
<213> Artificial sequence (Artificial sequence)
<400> 5
tgacattgat tattgactag ttattaatag taatcaatta cggggtcatt agttcatagc 60
ccatatatgg agttccgcgt tacataactt acggtaaatg gcccgcctgg ctgaccgccc 120
aacgaccccc gcccattgac gtcaataatg acgtatgttc ccatagtaac gccaataggg 180
actttccatt gacgtcaatg ggtggagtat ttacggtaaa ctgcccactt ggcagtacat 240
caagtgtatc atatgccaag tacgccccct attgacgtca atgacggtaa atggcccgcc 300
tggcattatg cccagtacat gaccttatgg gactttccta cttggcagta catctacgta 360
ttagtcatcg ctattaccat ggtgatgcgg ttttggcagt acatcaatgg gcgtggatag 420
cggtttgact cacggggatt tccaagtctc caccccattg acgtcaatgg gagtttgttt 480
tggcaccaaa atcaacggga ctttccaaaa tgtcgtaaca actccgcccc attgacgcaa 540
atgggcggta ggcgtgtacg gtgggaggtc tatataagca gagctcgttt agtgaaccgt 600
cagatcacta gaagctttat tgcggtagtt tatcacagtt aaattgctaa cgcagtcagt 660
gcttctgaca caacagtctc gaacttaagc tgcagaagtt ggtcgtgagg cactgggcag 720
gtaagtatca aggttacaag acaggtttaa ggagaccaat agaaactggg cttgtcgaga 780
cagagaagac tcttgcgttt ctgataggca cctattggtc ttactgacat ccactttgcc 840
tttctctcca caggtgtcca ctcccagttc aattacagct cttaaggcta gagtactcta 900
gcccgggatc caccggtcgc caccatgaag atggccagct ccgatgccaa tccctccgat 960
ggctccacag ccaatttagt gcccgaagtg aataacgagg tcatggcctt agagcccgtg 1020
gtgggagctg ctatcgctgc tcccgttgct ggacagcaga acgtgattga cccttggatt 1080
aggaataact tcgtgcaagc ccccggtggc gagtttaccg tcagccctcg taacgccccc 1140
ggtgagattc tgtggagcgc tcccctcggc cccgatctga atccctattt aagccatctg 1200
gccagaatgt acaacggata cgctggaggc ttcgaggtcc aagttattct ggccggcaac 1260
gccttcaccg ccggcaagat catcttcgcc gccgtgcccc ccaactttcc taccgagggc 1320
ctcagccctt cccaagttac catgttccct cacatcatcg tggacgtgag acagctggag 1380
cccgttctga tccctttacc cgatgttcgt aacaacttct accattacaa ccagagcaac 1440
gaccccacca tcaaactgat cgctatgctg tatacacctt taagagccaa caatgccggc 1500
gacgacgtgt tcaccgtgag ctgtagagtg ctcactcgtc ccagccccga ttttgacttc 1560
atttttttag tcccccccac cgtggaatct cgtaccaaac ccttcaccgt gcctattctc 1620
accgtggagg agatgaccaa ttctcgtttc cctatccctt tagagaaact gtttaccggc 1680
ccctccggcg ctttcgtggt gcaacctcag aacggtcgtt gtaccacaga cggcgtgctg 1740
ctgggcacaa cccagctgtc ccccgtgaac atctgtacct ttcgtggaga cgtgacccac 1800
atcgctggca cccaagaata taccatgaat ttagccagcc agaactggaa caactatgac 1860
cccaccgaag agatccccgc tcctctggga acccccgact tcgtcggaaa gattcaaggt 1920
gtgctgacac agaccaccag aggcgatgga agcactcgtg gacataaggc tacagtcagc 1980
accggcagcg tgcactttac acccaaactg ggcagcgtgc aattcagcac agacaccagc 2040
aacgacttcg agactggtca gaataccaag ttcacccccg tgggcgtggt gcaagatgga 2100
agcaccaccc accagaacga gccccagcag tgggttttac ccgattactc cggtcgtgac 2160
tcccataacg tccacctcgc ccccgctgtg gctcccacat tccccggtga gcagctgctc 2220
tttttcagaa gcaccatgcc cggatgcagc ggctacccca acatgaatct cgactgttta 2280
ctgcctcaag aatgggtgca gcacttctac caagaagctg cccccgctca gtccgatgtc 2340
gctttattac gtttcgtgaa ccccgatacc ggaagggttt tatttgagtg caagctgcat 2400
aagagcggat atgtgacagt ggctcacacc ggccagcacg atttagtgat cccccccaat 2460
ggctactttc gtttcgactc ttgggtgaat cagttctaca cactggcccc catgggcaac 2520
ggaaccggaa gaagaagagc tctctgaagc ggccgccact gtgctggatg atccgagctc 2580
ggtacctcta gagtcgaccc gggcggccaa accgctgatc agcctcgact gtgccttcta 2640
gttgccagcc atctgttgtt tgcccctccc ccgtgccttc cttgaccctg gaaggtgcca 2700
ctcccactgt cctttcctaa taaaatgagg aaattgcatc gcattgtctg agtaggtgtc 2760
attctattct ggggggtggg gtggggcagg acagcaaggg ggaggattgg gaagacaata 2820
gcaggcatgc tggggatgcg gtgggctcta tggcttctga ggcggaaaga accagcagat 2880
ctgcagatct 2890
<210> 6
<211> 34482
<212> DNA
<213> Artificial sequence (Artificial sequence)
<400> 6
atttaaatgg cgcgccgggc ccgggccgca tagttaagcc agccccgaca cccgccaaca 60
cccgctgacg cgccctgacg ggcttgtctg ctcccggcat ccgcttacag acaagctgtg 120
accgtctccg ggagctgcat gtgtcagagg ttttcaccgt catcaccgaa acgcgcgaga 180
cgaaagggcc tcgtgatacg cctattttta taggttaatg tcatgataat aatggtttct 240
tagacgtcag gtggcacttt tcggggaaat gtgcgcggaa cccctatttg tttatttttc 300
taaatacatt caaatatgta tccgctcatg agacaataac cctgataaat gcttcaataa 360
tattgaaaaa ggaagagtat gagtattcaa catttccgtg tcgcccttat tccctttttt 420
gcggcatttt gccttcctgt ttttgctcac ccagaaacgc tggtgaaagt aaaagatgct 480
gaagatcagt tgggtgcacg agtgggttac atcgaactgg atctcaacag cggtaagatc 540
cttgagagtt ttcgccccga agaacgtttt ccaatgatga gcacttttaa agttctgcta 600
tgtggcgcgg tattatcccg tattgacgcc gggcaagagc aactcggtcg ccgcatacac 660
tattctcaga atgacttggt tgagtactca ccagtcacag aaaagcatct tacggatggc 720
atgacagtaa gagaattatg cagtgctgcc ataaccatga gtgataacac tgcggccaac 780
ttacttctga caacgatcgg aggaccgaag gagctaaccg cttttttgca caacatgggg 840
gatcatgtaa ctcgccttga tcgttgggaa ccggagctga atgaagccat accaaacgac 900
gagcgtgaca ccacgatgcc tgtagcaatg gcaacaacgt tgcgcaaact attaactggc 960
gaactactta ctctagcttc ccggcaacaa ttaatagact ggatggaggc ggataaagtt 1020
gcaggaccac ttctgcgctc ggcccttccg gctggctggt ttattgctga taaatctgga 1080
gccggtgagc gtgggtctcg cggtatcatt gcagcactgg ggccagatgg taagccctcc 1140
cgtatcgtag ttatctacac gacggggagt caggcaacta tggatgaacg aaatagacag 1200
atcgctgaga taggtgcctc actgattaag cattggtaac tgtcagacca agtttactca 1260
tatatacttt agattgattt aaaacttcat ttttaattta aaaggatcta ggtgaagatc 1320
ctttttgata atctcatgac caaaatccct taacgtgagt tttcgttcca ctgagcgtca 1380
gaccccgtag aaaagatcaa aggatcttct tgagatcctt tttttctgcg cgtaatctgc 1440
tgcttgcaaa caaaaaaacc accgctacca gcggtggttt gtttgccgga tcaagagcta 1500
ccaactcttt ttccgaaggt aactggcttc agcagagcgc agataccaaa tactgttctt 1560
ctagtgtagc cgtagttagg ccaccacttc aagaactctg tagcaccgcc tacatacctc 1620
gctctgctaa tcctgttacc agtggctgct gccagtggcg ataagtcgtg tcttaccggg 1680
ttggactcaa gacgatagtt accggataag gcgcagcggt cgggctgaac ggggggttcg 1740
tgcacacagc ccagcttgga gcgaacgacc tacaccgaac tgagatacct acagcgtgag 1800
ctttgagata gcgccacgct tcccgaaggg agaaaggcgg acaggtatcc ggtaagcggc 1860
agggtcggaa caggagagcg cacgagggag cttccagggg gaaacgcctg gtatctttat 1920
agtcctgtcg ggtttcgcca cctctgactt gagcgtcgat ttttgtgatg ctcgtcaggg 1980
gggcggagcc tatggaaaaa cgccagcaac gcggcctttt tacggttcct ggccttttgc 2040
tggccttttg ctcacatgtt ctttcctgcg ttatcccctg attctgtgga taaccgtatt 2100
accgcctttg agtgagctga taccgctcgc cgcagccgaa cgaccgagcg cagcgagtca 2160
gtgagcgagg aagcggaaga gcgcccaata cgcaaaccgc ctctccccgc gcgttggccg 2220
attcattaat gcagctggca cgacaggttt cccgactgga tttaaatcat catcaataat 2280
atacctcaaa cttttggtgc gcgttaatat gcaaatgagg tgtttgaatt tggggatgcg 2340
gggcgctgat tggctgagag acgggcgacc gttaggggcg gggcgggtga cgttttgatg 2400
acgtggccgt gaggcggagc cggtttgcaa gttctcgtgg gaaaagtgac gtcaaacgag 2460
gtgtggtttg aacacggaaa tactcaattt tcccgcgctc tctgacagga aatgaggtgt 2520
ttctgggcgg atgcaagtga aaacgggcca ttttcgcgcg aaaactgaat gaggaagtga 2580
aaatctgagt aattccgcgt ttatggcagg gaggagtatt tgccgagggc cgagtagact 2640
ttgaccgatt acgtgggggt ttcgattacc gtatttttca cctaaatttc cgcgtacggt 2700
gtcaaagtcc ggtgttttta cgtaggcgtc agctgatcgc cagggtattt aaacctgcgc 2760
tctctagtca agaggccact cttgagtgcc agcgagtaga gttttctcct ccgcgccgcg 2820
agtcagatct acactttgaa aggcgatcgc cgatatcatt tccccgaaaa gtgccacctg 2880
accgtaacta taacggtcct aaggtagcga aagctcagat ctcccgatcc cctatggtgc 2940
actctcagta caatctgctc tgatgccgca tagttaagcc agtatctgct ccctgcttgt 3000
gtgttggagg tcgctgagta gtgcgcgagc aaaatttaag ctacaacaag gcaaggcttg 3060
accgacaatt gcatgaagaa tctgcttagg gttaggcgtt ttgcgctgct tcgcgatgta 3120
cgggccagat atacgcgttg acattgatta ttgactagtt attaatagta atcaattacg 3180
gggtcattag ttcatagccc atatatggag ttccgcgtta cataacttac ggtaaatggc 3240
ccgcctggct gaccgcccaa cgacccccgc ccattgacgt caataatgac gtatgttccc 3300
atagtaacgc caatagggac tttccattga cgtcaatggg tggagtattt acggtaaact 3360
gcccacttgg cagtacatca agtgtatcat atgccaagta cgccccctat tgacgtcaat 3420
gacggtaaat ggcccgcctg gcattatgcc cagtacatga ccttatggga ctttcctact 3480
tggcagtaca tctacgtatt agtcatcgct attaccatgg tgatgcggtt ttggcagtac 3540
atcaatgggc gtggatagcg gtttgactca cggggatttc caagtctcca ccccattgac 3600
gtcaatggga gtttgttttg gcaccaaaat caacgggact ttccaaaatg tcgtaacaac 3660
tccgccccat tgacgcaaat gggcggtagg cgtgtacggt gggaggtcta tataagcaga 3720
gctcgtttag tgaaccgtca gatcactaga agctttattg cggtagttta tcacagttaa 3780
attgctaacg cagtcagtgc ttctgacaca acagtctcga acttaagctg cagaagttgg 3840
tcgtgaggca ctgggcaggt aagtatcaag gttacaagac aggtttaagg agaccaatag 3900
aaactgggct tgtcgagaca gagaagactc ttgcgtttct gataggcacc tattggtctt 3960
actgacatcc actttgcctt tctctccaca ggtgtccact cccagttcaa ttacagctct 4020
taaggctaga gtactctagc ccgggatcca ccggtcgcca ccatgaagat ggccagctcc 4080
gatgccaatc cctccgatgg ctccacagcc aatttagtgc ccgaagtgaa taacgaggtc 4140
atggccttag agcccgtggt gggagctgct atcgctgctc ccgttgctgg acagcagaac 4200
gtgattgacc cttggattag gaataacttc gtgcaagccc ccggtggcga gtttaccgtc 4260
agccctcgta acgcccccgg tgagattctg tggagcgctc ccctcggccc cgatctgaat 4320
ccctatttaa gccatctggc cagaatgtac aacggatacg ctggaggctt cgaggtccaa 4380
gttattctgg ccggcaacgc cttcaccgcc ggcaagatca tcttcgccgc cgtgcccccc 4440
aactttccta ccgagggcct cagcccttcc caagttacca tgttccctca catcatcgtg 4500
gacgtgagac agctggagcc cgttctgatc cctttacccg atgttcgtaa caacttctac 4560
cattacaacc agagcaacga ccccaccatc aaactgatcg ctatgctgta tacaccttta 4620
agagccaaca atgccggcga cgacgtgttc accgtgagct gtagagtgct cactcgtccc 4680
agccccgatt ttgacttcat ttttttagtc ccccccaccg tggaatctcg taccaaaccc 4740
ttcaccgtgc ctattctcac cgtggaggag atgaccaatt ctcgtttccc tatcccttta 4800
gagaaactgt ttaccggccc ctccggcgct ttcgtggtgc aacctcagaa cggtcgttgt 4860
accacagacg gcgtgctgct gggcacaacc cagctgtccc ccgtgaacat ctgtaccttt 4920
cgtggagacg tgacccacat cgctggcacc caagaatata ccatgaattt agccagccag 4980
aactggaaca actatgaccc caccgaagag atccccgctc ctctgggaac ccccgacttc 5040
gtcggaaaga ttcaaggtgt gctgacacag accaccagag gcgatggaag cactcgtgga 5100
cataaggcta cagtcagcac cggcagcgtg cactttacac ccaaactggg cagcgtgcaa 5160
ttcagcacag acaccagcaa cgacttcgag actggtcaga ataccaagtt cacccccgtg 5220
ggcgtggtgc aagatggaag caccacccac cagaacgagc cccagcagtg ggttttaccc 5280
gattactccg gtcgtgactc ccataacgtc cacctcgccc ccgctgtggc tcccacattc 5340
cccggtgagc agctgctctt tttcagaagc accatgcccg gatgcagcgg ctaccccaac 5400
atgaatctcg actgtttact gcctcaagaa tgggtgcagc acttctacca agaagctgcc 5460
cccgctcagt ccgatgtcgc tttattacgt ttcgtgaacc ccgataccgg aagggtttta 5520
tttgagtgca agctgcataa gagcggatat gtgacagtgg ctcacaccgg ccagcacgat 5580
ttagtgatcc cccccaatgg ctactttcgt ttcgactctt gggtgaatca gttctacaca 5640
ctggccccca tgggcaacgg aaccggaaga agaagagctc tctgaagcgg ccgccactgt 5700
gctggatgat ccgagctcgg tacctctaga gtcgacccgg gcggccaaac cgctgatcag 5760
cctcgactgt gccttctagt tgccagccat ctgttgtttg cccctccccc gtgccttcct 5820
tgaccctgga aggtgccact cccactgtcc tttcctaata aaatgaggaa attgcatcgc 5880
attgtctgag taggtgtcat tctattctgg ggggtggggt ggggcaggac agcaaggggg 5940
aggattggga agacaatagc aggcatgctg gggatgcggt gggctctatg gcttctgagg 6000
cggaaagaac cagcagatct gcagatctga attcatctat gtcgggtgcg gagaaagagg 6060
taatgaaatg gcattatggg tattatgggt ctgcattaat gaatcggcca gatatcgaca 6120
tatgctggcc accgtacatg tggcttccca tgctcgcaag ccctggcccg agttcgagca 6180
caatgtcatg accaggtgca atatgcatct ggggtcccgg cgatcgcccg aggcatgttc 6240
atgccctacc agtgcaacat gcaatttgtg aaggtgctgc tggagcccga tgccatgtcc 6300
agagtgagcc tgacgggggt gtttgacatg aatgtggagc tgtggaaaat tctgagatat 6360
gatgaatcca agaccaggtg ccgggcctgc gaatgcggag gcaagcacgc caggcttcag 6420
cccgtgtgtg tggaggtgac ggaggacctg cgacccgatc atttggtgtt gtcctgcaac 6480
gggacggagt tcggctccag cggggaagaa tctgactaga gtgagtagtg tttgggggtg 6540
ggtgggagcc tgcatgatgg gcagaatgac taaaatctgt gtttttctgt gtgttgcagc 6600
agcatgagcg gaagcgcctc ctttgaggga ggggtattca gcccttatct gacggggcgt 6660
ctcccctcct gggcgggagt gcgtcagaat gtgatgggat ccacggtgga cggccggccc 6720
gtgcagcccg cgaactcttc aaccctgacc tacgcgaccc tgagctcctc gtccgtggac 6780
gcagctgccg ccgcagctgc tgcttccgcc gccagcgccg tgcgcggaat ggccctgggc 6840
gccggctact acagctctct ggtggccaac tcgagttcca ccaataatcc cgccagcctg 6900
aacgaggaga agctgttgct gctgatggcc cagctcgagg ccctgaccca gcgcctgggc 6960
gagctgaccc agcaggtggc tcagctgcag gcggagacgc gggccgcggt tgccacggtg 7020
aaaaccaaat aaaaaatgaa tcaataaata aacggagacg gttgttgatt ttaacacaga 7080
gtcttgaatc tttatttgat ttttcgcgcg cggtaggccc tggaccaccg gtctcgatca 7140
ttgagcaccc ggtggatctt ttccaggacc cggtagaggt gggcttggat gttgaggtac 7200
atgggcatga gcccgtcccg ggggtggagg tagctccatt gcagggcctc gtgctcgggg 7260
gtggtgttgt aaatcaccca gtcatagcag gggcgcaggg cgtggtgctg cacgatgtct 7320
ttgaggagga gactgatggc cacgggcagc cccttggtgt aggtgttgac gaacctattg 7380
agctgggagg gatgcatgcg gggggagatg agatgcatct tggcctggat cttgagattg 7440
gcgatgttcc cgcccagatc ccgccggggg ttcatgttgt gcaggaccac cagcacggtg 7500
tatccggtgc acttggggaa tttgtcatgc aacttggaag ggaaggcgtg aaagaatttg 7560
gagacgccct tgtgaccgcc caggttttcc atgcactcat ccatgatgat ggcgatgggc 7620
ccgtgggcgg cggcctgggc aaagacgttt cgggggtcgg acacatcgta gttgtggtcc 7680
tgggtgagct cgtcataggc cattttaatg aatttggggc ggagggtacc cgactggggg 7740
acaaaggtgc cctcgatccc gggggcgtag ttcccctcgc agatctgcat ctcccaggcc 7800
ttgagctcgg agggggggat catgtccacc tgcggggcga tgaaaaaaac ggtttccggg 7860
gcgggggaga tgagctgcgc cgaaagcagg ttccggagca gctgggactt gccgcagccg 7920
gtggggccgt agatgacccc gatgaccggc tgcaggtggt agttgaggga gagacagctg 7980
ccgtcctcgc ggaggagggg ggccacctcg ttcatcatct cgcgcacatg catgttctcg 8040
cgcacgagtt ccgccaggag gcgctcgccc cccagcgaga ggagctcttg cagcgaggcg 8100
aagtttttca gcggcttgag cccgtcggcc atgggcattt tggagagggt ctgttgcaag 8160
agttccagac ggtcccagag ctcggtgatg tgctctaggg catctcgatc cagcagacct 8220
cctcgtttcg cgggttgggg cgactgcggg agtagggcac caggcgatgg gcgtccagcg 8280
aggccagggt ccggtccttc cagggtcgca gggtccgcgt cagcgtggtc tccgtcacgg 8340
tgaaggggtg cgcgccgggc tgggcgcttg cgagggtgcg cttcaggctc atccggctgg 8400
tcgagaaccg ctcccggtcg gcgccctgcg cgtcggccag gtagcaattg agcatgagtt 8460
cgtagttgag cgcctcggcc gcgtggccct tggcgcggag cttacctttg gaagtgtgtc 8520
cgcagacggg acagaggagg gacttgaggg cgtagagctt gggggcgagg aagacggact 8580
cgggggcgta ggcgtccgcg ccgcagctgg cgcagacggt ctcgcactcc acgagccagg 8640
tgaggtcggg gcggtcgggg tcaaaaacga ggtttcctcc gtgctttttg atgcgtttct 8700
tacctctggt ctccatgagc tcgtgtcccc gctgggtgac aaagaggctg tccgtgtccc 8760
cgtagaccga ctttatgggc cggtcctcga gcggggtgcc gcggtcctcg tcgtagagga 8820
accccgccca ctccgagacg aaggcccggg tccaggccag cacgaaggag gccacgtggg 8880
aggggtagcg gtcgttgtcc accagcgggt ccaccttctc cagggtatgc aagcacatgt 8940
ccccctcgtc cacatccagg aaggtgattg gcttgtaagt gtaggccacg tgaccggggg 9000
tcccggccgg gggggtataa aagggggcgg gcccctgctc gtcctcactg tcttccggat 9060
cgctgtccag gagcgccagc tgttggggta ggtattccct ctcgaaggcg ggcatgacct 9120
cggcactcag gttgtcagtt tctagaaacg aggaggattt gatattgacg gtgccgttgg 9180
agacgccttt catgagcccc tcgtccatct ggtcagaaaa gacgatcttt ttgttgtcga 9240
gcttggtggc gaaggagccg tagagggcgt tggagagcag cttggcgatg gagcgcatgg 9300
tctggttctt ttccttgtcg gcgcgctcct tggcggcgat gttgagctgc acgtactcgc 9360
gcgccacgca cttccattcg gggaagacgg tggtgagctc gtcgggcacg attctgaccc 9420
gccagccgcg gttgtgcagg gtgatgaggt ccacgctggt ggccacctcg ccgcgcaggg 9480
gctcgttggt ccagcagagg cgcccgccct tgcgcgagca gaaggggggc agcgggtcca 9540
gcatgagctc gtcggggggg tcggcgtcca cggtgaagat gccgggcagg agctcggggt 9600
cgaagtagct gatgcaggtg cccagatcgt ccagacttgc ttgccagtcg cgcacggcca 9660
gcgcgcgctc gtaggggctg aggggcgtgc cccagggcat ggggtgcgtg agcgcggagg 9720
cgtacatgcc gcagatgtcg tagacgtaga ggggctcctg gaggacgccg atgtaggtgg 9780
ggtagcagcg ccccccgcgg atgctggcgc gcacgtagtc gtacagctcg tgcgagggcg 9840
cgaggagccc cgtgccgaga ttggagcgct gcggcttttc ggcgcggtag acgatctggc 9900
ggaagatggc gtgggagttg gaggagatgg tgggcctctg gaagatgttg aagtgggcat 9960
ggggcagtcc gaccgagtcc ctgatgaagt gggcgtagga gtcctgcagc ttggcgacga 10020
gctcggcggt gacgaggacg tccagggcgc agtagtcgag ggtctcttgg atgatgtcgt 10080
acttgagctg gcccttctgc ttccacagct cgcggttgag aaggaactct tcgcggtcct 10140
tccagtactc ttcgaggggg aacccgtcct gatcggcacg gtaagagccc accatgtaga 10200
actggttgac ggccttgtag gcgcagcagc ccttctccac ggggagggcg taagcttgcg 10260
cggccttgcg cagggaggtg tgggtgaggg cgaaggtgtc gcgcaccatg actttgagga 10320
actggtgctt gaagtcgagg tcgtcgcagc cgccctgctc ccagagctgg aagtccgtgc 10380
gcttcttgta ggcggggttg ggcaaagcga aagtaacatc gttgaagagg atcttgcccg 10440
cgcggggcat gaagttgcga gtgatgcgga aaggctgggg cacctcggcc cggttgttga 10500
tgacctgggc ggcgaggacg atctcgtcga agccgttgat gttgtgcccg acgatgtaga 10560
gttccacgaa tcgcgggcgg cccttgacgt ggggcagctt cttgagctcg tcgtaggtga 10620
gctcggcggg gtcgctgagc ccgtgctgct cgagggccca gtcggcgacg tgggggttgg 10680
cgctgaggaa ggaagtccag agatccacgg ccagggcggt ctgcaagcgg tcccggtact 10740
gacggaactg ctggcccacg gccatttttt cgggggtgac gcagtagaag gtgcgggggt 10800
cgccgtgcca gcggtcccac ttgagctgga gggcgaggtc gtgggcgagc tcgacgagcg 10860
gcgggtcccc ggagagtttc atgaccagca tgaaggggac gagctgcttg ccgaaggacc 10920
ccatccaggt gtaggtttcc acatcgtagg tgaggaagag cctttcggtg cgaggatgcg 10980
agccgatggg gaagaactgg atctcctgcc accagttgga ggaatggctg ttgatgtgat 11040
ggaagtagaa atgccgacgg cgcgccgagc actcgtgctt gtgtttatac aagcgtccgc 11100
agtgctcgca acgctgcacg ggatgcacgt gctgcacgag ctgtacctgg gttcctttga 11160
cgaggaattt cagtgggcag tggagcgctg gcggctgcat ctggtgctgt actacgtcct 11220
ggccatcggc gtggccatcg tctgcctcga tggtggtcat gctgacgagc ccgcgcggga 11280
ggcaggtcca gacctcggct cggacgggtc ggagagcgag gacgagggcg cgcaggccgg 11340
agctgtccag ggtcctgaga cgctgcggag tcaggtcagt gggcagcggc ggcgcgcggt 11400
tgacttgcag gagcttttcc agggcgcgcg ggaggtccag atggtacttg atctccacgg 11460
cgccgttggt ggcgacgtcc acggcttgca gggtcccgtg cccctggggc gccaccaccg 11520
tgccccgttt cttcttgggc ggcggcggct ccatgcttag aagcggcggc gaggacgcgc 11580
gccgggcggc aggggcggct cggggcccgg aggcaggggc ggcaggggca cgtcggcgcc 11640
gcgcgcgggc aggttctggt actgcgcccg gagaagactg gcgtgagcga cgacgcgacg 11700
gttgacgtcc tggatctgac gcctctgggt gaaggccacg ggacccgtga gtttgaacct 11760
gaaagagagt tcgacagaat caatctcggt atcgttgacg gcggcctgcc gcaggatctc 11820
ttgcacgtcg cccgagttgt cctggtaggc gatctcggtc atgaactgct cgatctcctc 11880
ctcctgaagg tctccgcggc cggcgcgctc gacggtggcc gcgaggtcgt tggagatgcg 11940
gcccatgagc tgcgagaagg cgttcatgcc ggcctcgttc cagacgcggc tgtagaccac 12000
ggctccgtcg gggtcgcgcg cgcgcatgac cacctgggcg aggttgagct cgacgtggcg 12060
cgtgaagacc gcgtagttgc agaggcgctg gtagaggtag ttgagcgtgg tggcgatgtg 12120
ctcggtgacg aagaagtaca tgatccagcg gcggagcggc atctcgctga cgtcgcccag 12180
ggcttccaag cgctccatgg cctcgtagaa gtccacggcg aagttgaaaa actgggagtt 12240
gcgcgccgag acggtcaact cctcctccag aagacggatg agctcggcga tggtggcgcg 12300
cacctcgcgc tcgaaggccc cggggggctc ctcttccatt tcctcctctt cctcctccac 12360
taacatctct tctacttcct cctcaggagg cggcggcggg ggaggggccc tgcgtcgccg 12420
gcggcgcacg ggcagacggt cgatgaagcg ctcgatggtc tccccgcgcc ggcgacgcat 12480
ggtctcggtg acggcgcgcc cgtcctcgcg gggccgcagc gtgaagacgc cgccgcgcat 12540
ctccaggtgg ccgccggggg ggtctccgtt gggcagggag agggcgctga cgatgcatct 12600
tatcaattga cccgtaggga ctccgcgcaa ggacctgagc gtctcgagat ccacgggatc 12660
cgaaaaccgc tgaacgaagg cttcgagcca gtcgcagtcg caaggtaggc tgagcccggt 12720
ttcttgttct tcgggtattt ggtcgggagg cgggcgggcg atgctgctgg tgatgaagtt 12780
gaagtaggcg gtcctgagac ggcggatggt ggcgaggagc accaggtcct tgggcccggc 12840
ttgctggatg cgcagacggt cggccatgcc ccaggcgtgg tcctgacacc tggcgaggtc 12900
cttgtagtag tcctgcatga gccgctccac gggcacctcc tcctcgcccg cgcggccgtg 12960
catgcgcgtg agcccgaacc cgcgctgcgg ctggacgagc gccaggtcgg cgacgacgcg 13020
ctcggcgagg atggcctgct ggatctgggt gagggtggtc tggaagtcgt cgaagtcgac 13080
gaagcggtgg taggctccgg tgttgatggt gtaggagcag ttggccatga cggaccagtt 13140
gacggtctgg tggccggggc gcacgagctc gtggtacttg aggcgcgagt aggcgcgcgt 13200
gtcgaagatg tagtcgttgc aggtgcgcac gaggtactgg tatccgacga ggaagtgcgg 13260
cggcggctgg cggtagagcg gccatcgctc ggtggcgggg gcgccgggcg cgaggtcctc 13320
gagcatgagg cggtggtagc cgtagatgta cctggacatc caggtgatgc cggcggcggt 13380
ggtggaggcg cgcgggaact cgcggacgcg gttccagatg ttgcgcagcg gcaggaagta 13440
gttcatggtg gccgcggtct ggcccgtgag gcgcgcgcag tcgtggatgc tctagacata 13500
cgggcaaaaa cgaaagcggt cagcggctcg actccgtggc ctggaggcta agcgaacggg 13560
ttgggctgcg cgtgtacccc ggttcgaatc tcgaatcagg ctggagccgc agctaacgtg 13620
gtactggcac tcccgtctcg acccaagcct gctaacgaaa cctccaggat acggaggcgg 13680
gtcgtttttt ggccttggtc gctggtcatg aaaaactagt aagcgcggaa agcggccgcc 13740
cgcgatggct cgctgccgta gtctggagaa agaatcgcca gggttgcgtt gcggtgtgcc 13800
ccggttcgag cctcagcgct cggcgccggc cggattccgc ggctaacgtg ggcgtggctg 13860
ccccgtcgtt tccaagaccc cttagccagc cgacttctcc agttacggag cgagcccctc 13920
tttttttctt gtgtttttgc cagatgcatc ccgtactgcg gcagatgcgc ccccaccctc 13980
caccacaacc gcccctaccg cagcagcagc aacagccggc gcttctgccc ccgccccagc 14040
agcagcagcc agccactacc gcggcggccg ccgtgagcgg agccggcgtt cagtatgacc 14100
tggccttgga agagggcgag gggctggcgc ggctgggggc gtcgtcgccg gagcggcacc 14160
cgcgcgtgca gatgaaaagg gacgctcgcg aggcctacgt gcccaagcag aacctgttca 14220
gagacaggag cggcgaggag cccgaggaga tgcgcgcctc ccgcttccac gcggggcggg 14280
agctgcggcg cggcctggac cgaaagcggg tgctgaggga cgaggatttc gaggcggacg 14340
agctgacggg gatcagcccc gcgcgcgcgc acgtggccgc ggccaacctg gtcacggcgt 14400
acgagcagac cgtgaaggag gagagcaact tccaaaaatc cttcaacaac cacgtgcgca 14460
cgctgatcgc gcgcgaggag gtgaccctgg gcctgatgca cctgtgggac ctgctggagg 14520
ccatcgtgca gaaccccacg agcaagccgc tgacggcgca gctgtttctg gtggtgcagc 14580
acagtcggga caacgagacg ttcagggagg cgctgctgaa tatcaccgag cccgagggcc 14640
gctggctcct ggacctggtg aacattctgc agagcatcgt ggtgcaggag cgcgggctgc 14700
cgctgtccga gaagctggcg gccatcaact tctcggtgct gagcctgggc aagtactacg 14760
ctaggaagat ctacaagacc ccgtacgtgc ccatagacaa ggaggtgaag atcgatgggt 14820
tttacatgcg catgaccctg aaagtgctga ccctgagcga cgatctgggg gtgtaccgca 14880
acgacaggat gcaccgcgcg gtgagcgcca gccgccggcg cgagctgagc gaccaggagc 14940
tgatgcacag cctgcagcgg gccctgaccg gggccgggac cgagggggag agctactttg 15000
acatgggcgc ggacctgcgc tggcagccca gccgccgggc cttggaagct gccggcggcg 15060
tgccctacgt ggaggaggtg gacgatgagg aggaggaggg cgagtacctg gaagactgat 15120
ggcgcgaccg tatttttgct agatgcagca acagccaccg ccgccgcctc ctgatcccgc 15180
gatgcgggcg gcgctgcaga gccagccgtc cggcattaac tcctcggacg attggaccca 15240
ggccatgcaa cgcatcatgg cgctgacgac ccgcaatccc gaagccttta gacagcagcc 15300
tcaggccaac cggctctcgg ccatcctgga ggccgtggtg ccctcgcgct cgaaccccac 15360
gcacgagaag gtgctggcca tcgtgaacgc gctggtggag aacaaggcca tccgcggcga 15420
cgaggccggg ctggtgtaca acgcgctgct ggagcgcgtg gcccgctaca acagcaccaa 15480
cgtgcagacg aacctggacc gcatggtgac cgacgtgcgc gaggcggtgt cgcagcgcga 15540
gcggttccac cgcgagtcga acctgggctc catggtggcg ctgaacgcct tcctgagcac 15600
gcagcccgcc aacgtgcccc ggggccagga ggactacacc aacttcatca gcgcgctgcg 15660
gctgatggtg gccgaggtgc cccagagcga ggtgtaccag tcggggccgg actacttctt 15720
ccagaccagt cgccagggct tgcagaccgt gaacctgagc caggctttca agaacttgca 15780
gggactgtgg ggcgtgcagg ccccggtcgg ggaccgcgcg acggtgtcga gcctgctgac 15840
gccgaactcg cgcctgctgc tgctgctggt ggcgcccttc acggacagcg gcagcgtgag 15900
ccgcgactcg tacctgggct acctgcttaa cctgtaccgc gaggccatcg ggcaggcgca 15960
cgtggacgag cagacctacc aggagatcac ccacgtgagc cgcgcgctgg gccaggagga 16020
cccgggcaac ctggaggcca ccctgaactt cctgctgacc aaccggtcgc agaagatccc 16080
gccccagtac gcgctgagca ccgaggagga gcgcatcctg cgctacgtgc agcagagcgt 16140
ggggctgttc ttgatgcagg agggggccac gcccagcgcc gcgctcgaca tgaccgcgcg 16200
caacatggag cccagcatgt acgcccgcaa ccgcccgttc atcaataagc tgatggacta 16260
cttgcatcgg gcggccgcca tgaactcgga ctactttacc aacgccatct tgaacccgca 16320
ctggctcccg ccgcccgggt tctacacggg cgagtacgac atgcccgacc ccaacgacgg 16380
gttcctgtgg gacgacgtgg acagcagcgt gttctcgccg cggcccacca ccaccaccgt 16440
gtggaagaaa gagggcgggg accggcggcc gtcctcggcg ctgtccggtc gcgcgggtgc 16500
tgccgcggcg gtgcccgagg ctgccagccc cttcccgagc ctgccctttt cgctgaacag 16560
cgtgcgcagc agcgagctgg gtcggctgac gcggccgcgc ctgctgggcg aggaggagta 16620
cctgaacgac tccttgttga agcccgagcg cgagaagaac ttccccaata acgggataga 16680
gagcctggtg gacaagatga gccgctggaa gacgtacgcg cacgagcaca gggacgagcc 16740
ccgagctagc agcgcaggca cccgtagacg ccagcggcac gacaggcagc ggggactggt 16800
gtgggacgat gaggattccg ccgacgacag cagcgtgttg gacttgggtg ggagtggtgg 16860
tggtaacccg ttcgctcacc tgcgcccccg tatcgggcgc ctgatgtaag aatctgaaaa 16920
aataaaagac ggtactcacc aaggccatgg cgaccagcgt gcgttcttct ctgttgtttg 16980
tagtagtatg atgaggcgcg tgtacccgga gggtcctcct ccctcgtacg agagcgtgat 17040
gcagcaggcg gtggcggcgg cgatgcagcc cccgctggag gcgccttacg tgcccccgcg 17100
gtacctggcg cctacggagg ggcggaacag cattcgttac tcggagctgg cacccttgta 17160
cgataccacc cggttgtacc tggtggacaa caagtcggcg gacatcgcct cgctgaacta 17220
ccagaacgac cacagcaact tcctgaccac cgtggtgcag aacaacgatt tcacccccac 17280
ggaggccagc acccagacca tcaactttga cgagcgctcg cggtggggcg gccagctgaa 17340
aaccatcatg cacaccaaca tgcccaacgt gaacgagttc atgtacagca acaagttcaa 17400
ggcgcgggtg atggtctcgc gcaagacccc caacggggtc acggtagggg atgattatga 17460
tggtagtcag gacgagctga cctacgagtg ggtggagttt gagctgcccg agggcaactt 17520
ctcggtgacc atgaccatcg atctgatgaa caacgccatc atcgacaact acttggcggt 17580
ggggcggcag aacggggtgc tggagagcga catcggcgtg aagttcgaca cgcgcaactt 17640
ccggctgggc tgggaccccg tgaccgagct ggtgatgccg ggcgtgtaca ccaacgaggc 17700
cttccacccc gacatcgtcc tgctgcccgg ctgcggcgtg gacttcaccg agagccgcct 17760
cagcaacctg ctgggcatcc gcaagcggca gcccttccag gagggcttcc agatcctgta 17820
cgaggacctg gaggggggca acatccccgc gctcttggat gtcgaagcct atgaagaaag 17880
taaggaaaaa gcagaggctg aggcaactac agccgtggct accgccgcga ctgtggcaga 17940
tgccactgtc accaggggcg atacattcgc cacccaggcg gaggaagcag ccgccctagc 18000
ggcgaccgat gatagtgaaa gtaagatagt catcaagccg gtggagaagg acagcaagaa 18060
caggagctac aacgttctac cggatggaaa gaacaccgcc taccgcagct ggtacctggc 18120
ctacaactac ggcgaccccg agaagggcgt gcgctcctgg acgctgctca ccacctcgga 18180
cgtcacctgc ggcgtggagc aagtctactg gtcgctgccc gacatgatgc aagacccggt 18240
caccttccgc tccacgcgac aagttagcaa ctacccggtg gtgggcgccg agctcctgcc 18300
cgtctactcc aagagcttct tcaacgagca ggccgtctac tcgcagcagc tgcgtgcctt 18360
cacctcgctc acgcacgtct tcaaccgctt ccccgagaac cagatcctcg tccgcccgcc 18420
cgcgcccacc attaccaccg tcagtgaaaa cgttcctgct ctcacagatc acgggaccct 18480
gccgctgcgc agcagtatcc ggggagtcca gcgcgtgacc gtcactgacg ccagacgccg 18540
cacctgcccc tacgtctaca aggccctggg cgtagtcgcg ccgcgcgtcc tctcgagccg 18600
caccttctaa aaaatgtcca ttctcatctc gcccagtaat aacaccggtt ggggcctgcg 18660
cgcgcccagc aagatgtacg gaggcgctcg ccaacgctcc acgcaacacc ccgtgcgcgt 18720
gcgcgggcac ttccgcgctc cctggggcgc cctcaagggc cgcgtgcgct cgcgcaccac 18780
cgtcgacgac gtgatcgacc aggtggtggc cgacgcgcgc aactacacgc ccgccgccgc 18840
gcccgcctcc accgtggacg ccgtcatcga cagcgtggtg gccgacgcgc gccggtacgc 18900
ccgcgccaag agccggcggc ggcgcatcgc ccggcggcac cggagcaccc ccgccatgcg 18960
cgcggcgcga gccttgctgc gcagggccag gcgcacggga cgcagggcca tgctcagggc 19020
ggccagacgc gcggcctccg gcagcagcag cgccggcagg acccgcagac gcgcggccac 19080
ggcggcggcg gcggccatcg ccagcatgtc ccgcccgcgg cgcggcaacg tgtactgggt 19140
gcgcgacgcc gccaccggtg tgcgcgtgcc cgtgcgcacc cgcccccctc gcacttgaag 19200
atgctgactt cgcgatgttg atgtgtccca gcggcgagga ggatgtccaa gcgcaaatac 19260
aaggaagaga tgctccaggt catcgcgcct gagatctacg gccccgcggc ggcggtgaag 19320
gaggaaagaa agccccgcaa actgaagcgg gtcaaaaagg acaaaaagga ggaggaagat 19380
gacggactgg tggagtttgt gcgcgagttc gccccccggc ggcgcgtgca gtggcgcggg 19440
cggaaagtga aaccggtgct gcggcccggc accacggtgg tcttcacgcc cggcgagcgt 19500
tccggctccg cctccaagcg ctcctacgac gaggtgtacg gggacgagga catcctcgag 19560
caggcggtcg agcgtctggg cgagtttgct tacggcaagc gcagccgccc cgcgcccttg 19620
aaagaggagg cggtgtccat cccgctggac cacggcaacc ccacgccgag cctgaagccg 19680
gtgaccctgc agcaggtgct gccgagcgcg gcgccgcgcc ggggcttcaa gcgcgagggc 19740
ggcgaggatc tgtacccgac catgcagctg atggtgccca agcgccagaa gctggaggac 19800
gtgctggagc acatgaaggt ggaccccgag gtgcagcccg aggtcaaggt gcggcccatc 19860
aagcaggtgg ccccgggcct gggcgtgcag accgtggaca tcaagatccc cacggagccc 19920
atggaaacgc agaccgagcc cgtgaagccc agcaccagca ccatggaggt gcagacggat 19980
ccctggatgc cagcggcttc caccaccacc actcgccgaa gacgcaagta cggcgcggcc 20040
agcctgctga tgcccaacta cgcgctgcat ccttccatca tccccacgcc gggctaccgc 20100
ggcacgcgct tctaccgcgg ctacaccagc agccgccgcc gcaagaccac cacccgccgc 20160
cgtcgtcgca gccgccgcag cagcaccgcg acttccgcct tggtgcggag agtgtatcgc 20220
agcgggcgcg agcctctgac cctgccgcgc gcgcgctacc acccgagcat cgccatttaa 20280
ctaccgcctc ctacttgcag atatggccct cacatgccgc ctccgcgtcc ccattacggg 20340
ctaccgagga agaaagccgc gccgtagaag gctgacgggg aacgggctgc gtcgccatca 20400
ccaccggcgg cggcgcgcca tcagcaagcg gttgggggga ggcttcctgc ccgcgctgat 20460
ccccatcatc gccgcggcga tcggggcgat ccccggcata gcttccgtgg cggtgcaggc 20520
ctctcagcgc cactgagaca caaaaaagca tggatttgta ataaaaaaat ggactgacgc 20580
tcctggtcct gtgatgtgtg tttttagatg gaagacatca atttttcgtc cctggcaccg 20640
cgacacggca cgcggccgtt tatgggcacc tggagcgaca tcggcaacag ccaactgaac 20700
gggggcgcct tcaattggag cagtctctgg agcgggctta agaatttcgg gtccacgctc 20760
aaaacctatg gcaacaaggc gtggaacagc agcacagggc aggcgctgag ggaaaagctg 20820
aaagagcaga acttccagca gaaggtggtc gatggcctgg cctcgggcat caacggggtg 20880
gtggacctgg ccaaccaggc cgtgcagaaa cagatcaaca gccgcctgga cgcggtcccg 20940
cccgcggggt ccgtggagat gccccaggtg gaggaggagc tgcctcccct ggacaagcgc 21000
ggcgacaagc gaccgcgtcc cgacgcggag gagacgctgc tgacgcacac ggacgagccg 21060
cccccgtacg aggaggcggt gaaactgggt ctgcccacca cgcggcccgt ggcgcctctg 21120
gccaccgggg tgctgaaacc cagcagcagc agccagcccg cgaccctgga cttgcctccg 21180
cctgcttccc gcccctccac agtggctaag cccctgccgc cggtggccgt cgcgtcgcgc 21240
gccccccgag gccgccccca ggcgaactgg cagagcactc tgaacagcat cgtgggtctg 21300
ggagtgcaga gtgtgaagcg ccgccgctgc tattaaaaga cactgtagcg cttaacttgc 21360
ttgtctgtgt gtgtatatgt atgtccgccg accagaagga ggaagaggcg cgtcgccgag 21420
ttgcaagatg gccaccccat cgatgctgcc ccagtgggcg tacatgcaca tcgccggaca 21480
ggacgcttcg gagtacctga gtccgggtct ggtgcagttc gcccgcgcca cagacaccta 21540
cttcagtctg gggaacaagt ttaggaaccc cacggtggcg cccacgcacg atgtgaccac 21600
cgaccgcagc cagcggctga cgctgcgctt cgtgcccgtg gaccgcgagg acaacaccta 21660
ctcgtacaaa gtgcgctaca cgctggccgt gggcgacaac cgcgtgctgg acatggccag 21720
cacctacttt gacatccgcg gcgtgctgga tcggggcccc agcttcaaac cctactccgg 21780
caccgcctac aacagcctag ctcccaaggg agcgcccaac acctcacagt ggaaggattc 21840
cgacagcaaa atgcatactt ttggagttgc tgccatgccc ggtgttgttg gtaaaaaaat 21900
agaagccgat ggtctgccta ttggaataga ttcatcctct ggaactgaca ccataattta 21960
tgctgataaa actttccaac cagagccaca ggttggaagt gacagttggg tcgacaccaa 22020
tggtgcagag gaaaaatatg gaggtagagc tcttaaggac actacaaaca tgaagccctg 22080
ctacggttct tttgccaggc ctaccaacaa agaaggtgga caggctaaca taaaagattc 22140
tgaaactgcc agcactactc ctaactatga tatagatttg gcattctttg acagcaaaaa 22200
tattgcagct aactacgatc cagatattgt aatgtacaca gaaaatgttg agttgcaaac 22260
tccagatact catattgtgt ttaagccagg aacttcagat gaaagttcag aagccaattt 22320
gggccagcag gccatgccca acagacccaa ctacatcggg ttcagagaca actttatcgg 22380
gctcatgtac tacaacagca ctggcaatat gggtgtactg gctggtcagg cctcccagct 22440
aaatgctgtg gtggacttgc aggacagaaa caccgaactg tcctaccagc tcttgcttga 22500
ctctctgggt gacagaacca ggtatttcag tatgtggaat caggcggtgg acagctatga 22560
ccccgatgtg cgcattattg aaaatcacgg tgtggaggat gaactcccca attattgctt 22620
ccctttgaat ggtgtaggct ttacagatac ttaccagggt gttaaagtta agacagatac 22680
agccgctact ggtaccaatg gaacgcagtg ggacaaagat gataccacag tcagcactgc 22740
caatgagatc cactcaggca atcctttcgc catggagatc aacatccagg ccaacctgtg 22800
gcggaacttc ctctacgcga acgtggcgct gtacctgccc gactcctaca agtacacgcc 22860
ggccaacatc acgctgccga ccaacaccaa cacctacgat tacatgaacg gccgcgtggt 22920
ggcgccctcg ctggtggacg cctacatcaa catcggggcg cgctggtcgc tggaccccat 22980
ggacaacgtc aaccccttca accaccaccg caacgcgggc ctgcgctacc gctccatgct 23040
cctgggcaac gggcgctacg tgcccttcca catccaggtg ccccaaaagt ttttcgccat 23100
caagagcctc ctgctcctgc ccgggtccta cacctacgag tggaacttcc gcaaggacgt 23160
caacatgatc ctgcagagct ccctcggcaa cgacctgcgc acggacgggg cctccatcgc 23220
cttcaccagc atcaacctct acgccacctt cttccccatg gcgcacaaca ccgcctccac 23280
gctcgaggcc atgctgcgca acgacaccaa cgaccagtcc ttcaacgact acctctcggc 23340
ggccaacatg ctctacccca tcccggccaa cgccaccaac gtgcccatct ccatcccctc 23400
gcgcaactgg gccgccttcc gcggatggtc cttcacgcgc ctcaagaccc gcgagacgcc 23460
ctcgctcggc tccgggttcg acccctactt cgtctactcg ggctccatcc cctacctcga 23520
cggcaccttc tacctcaacc acaccttcaa gaaggtctcc atcaccttcg actcctccgt 23580
cagctggccc ggcaacgacc gcctcctgac gcccaacgag ttcgaaatca agcgcaccgt 23640
cgacggagag ggatacaacg tggcccagtg caacatgacc aaggactggt tcctggtcca 23700
gatgctggcc cactacaaca tcggctacca gggcttctac gtgcccgagg gctacaagga 23760
ccgcatgtac tccttcttcc gcaacttcca gcccatgagc cgccaggtcg tggacgaggt 23820
caactacaag gactaccagg ccgtcaccct ggcctaccag cacaacaact cgggcttcgt 23880
cggctacctc gcgcccacca tgcgccaggg ccagccctac cccgccaact acccctaccc 23940
gctcatcggc aagagcgccg tcgccagcgt cacccagaaa aagttcctct gcgaccgggt 24000
catgtggcgc atccccttct ccagcaactt catgtccatg ggcgcgctca ccgacctcgg 24060
ccagaacatg ctctacgcca actccgccca cgcgctagac atgaatttcg aagtcgaccc 24120
catggatgag tccacccttc tctatgttgt cttcgaagtc ttcgacgtcg tccgagtgca 24180
ccagccccac cgcggcgtca tcgaggccgt ctacctgcgc acgcccttct cggccggcaa 24240
cgccaccacc taaagccccg ctcttgcttc ttgcaagatg acggcctgtg gctccggcga 24300
gcaggagctc agggccatcc tccgcgacct gggctgcggg ccctgcttcc tgggcacctt 24360
cgacaagcgc ttcccgggat tcatggcccc gcacaagctg gcctgcgcca tcgtcaacac 24420
ggccggccgc gagaccgggg gcgagcactg gctggccttc gcctggaacc cgcgctccca 24480
cacctgctac ctcttcgacc ccttcgggtt ctcggacgag cgcctcaagc agatctacca 24540
gttcgagtac gagggcctgc tgcgccgcag cgccctggcc accgaggacc gctgcatcac 24600
cctggaaaag tccacccaga ccgtgcaggg tccgcgctcg gccgcctgcg ggctcttctg 24660
ctgcatgttc ctgcacgcct tcgtgcactg gcccgaccgc cccatggaca agaaccccac 24720
catgaacttg ctgacggggg tgcccaacgg catgctccag tcgccccagg tggaacccac 24780
cctgcgccgc aaccaggagg cgctctaccg cttcctcaac gcccactccg cctactttcg 24840
ctcccaccgc gcgcgcatcg agaaggccac cgccttcgac cgcatgaatc aagacatgta 24900
aactgtgtgt atgtgaatgc tttattcatc ataataaaca gcacatgttt atgccacctt 24960
ctctgaggct ctgactttat ttagaaatcg aaggggttct gccggctctc ggcgtgcccc 25020
gcgggcaggg atacgttgcg gaactggtac ttgggcagcc acttgaactc ggggatcagc 25080
agcttcggca cggggaggtc ggggaacgag tcgctccaca gcttgcgcgt gagttgcagg 25140
gcgcccagca ggtcgggcgc ggagatcttg aaatcgcagt tgggacccgc gttctgcgcg 25200
cgagagttgc ggtacacggg gttgcagcac tggaacacca tcagggccgg gtgcttcacg 25260
ctcgccagca ccgtcgcgtc ggtgatgccc tccacgtcca gatcctcggc gttggccatc 25320
ccgaaggggg tcatcttgca ggtctgccgc cccatgctgg gcacgcagcc gggcttgtgg 25380
ttgcaatcgc agtgcagggg gatcagcatc atctgagcct gctcggagct catgcccggg 25440
tacatggcct tcatgaaagc ctccagctgg cggaaggcct gctgcgcctt gccgccctcg 25500
gtgaagaaga ccccacagga cttgctagag aactggttgg tggcgcagcc cgcgtcgtgc 25560
acgcagcagc gcgcgtcgtt gttggccagc tgcaccacgc tgcgccccca gcggttctgg 25620
gtgatcttgg cccggtcggg gttctccttc agcgcgcgct gcccgttctc gctcgccaca 25680
tccatctcga tcgtgtgctc cttctggatc atcacggtcc cgtgcaggca ccgcagcttg 25740
ccctcggcct cggtgcaccc gtgcagccac agcgcgcagc cggtgcactc ccagttcttg 25800
tgggcgatct gggagtgcga gtgcacgaag ccctgcagga agcggcccat catcgtggtc 25860
agggtcttgt tgctggtgaa ggtcagcggg atgccgcggt gctcctcgtt cacatacagg 25920
tggcagatgc ggcggtacac ctcgccctgc tcgggcatca gctggaaggc ggacttcagg 25980
tcgctctcca cgcggtaccg ctccatcagc agcgtcatca cttccatgcc cttctcccag 26040
gccgaaacga tcggcaggct cagggggttc ttcaccgtca tcttagtcgc cgccgccgaa 26100
gtcagggggt cgttctcgtc cagggtctca aacactcgct tgccgtcctt ctcggtgatg 26160
cgcacggggg gaaagctgaa gcccacggcc gccagctcct cctcggcctg cctttcgtcc 26220
tcgctgtcct ggctgatgtc ttgcaaaggc acatgcttgg tcttgcgggg tttctttttg 26280
ggcggcagag gcggcggcgg agacgtgctg ggcgagcgcg agttctcgct caccacgact 26340
atttcttctt cttggccgtc gtccgagacc acgcggcggt aggcatgcct cttctggggc 26400
agaggcggag gcgacgggct ctcgcggttc ggcgggcggc tggcagagcc ccttccgcgt 26460
tcgggggtgc gctcctggcg gcgctgctct gactgacttc ctccgcggcc ggccattgtg 26520
ttctcctagg gagcaacaag catggagact cagccatcgt cgccaacatc gccatctgcc 26580
cccgccgccg acgagaacca gcagcagcag aatgaaagct taaccgcccc gccgcccagc 26640
cccacctccg acgccgccgc ggccccagac atgcaagaga tggaggaatc catcgagatt 26700
gacctgggct acgtgacgcc cgcggagcac gaggaggagc tggcagcgcg cttttcagcc 26760
ccggaagaga accaccaaga gcagccagag caggaagcag agagcgagca gcagcaggct 26820
gggctcgagc atggcgacta cctgagcggg gcagaggacg tgctcatcaa gcatctggcc 26880
cgccaaagca tcatcgtcaa ggacgcgctg ctcgaccgcg ccgaggtgcc cctcagcgtg 26940
gcggagctca gccgcgccta cgagcgcaac ctcttctcgc cgcgcgtgcc ccccaagcgc 27000
cagcccaacg gcacctgcga gcccaacccg cgcctcaact tctacccggt cttcgcggtg 27060
cccgaggccc tggccaccta ccacctcttt ttcaagaacc aaaggatccc cgtctcctgc 27120
cgcgccaacc gcacccgcgc cgacgccctg ctcaacctgg gtcccggcgc ccgcctacct 27180
gatatcacct ccttggaaga ggttcccaag atcttcgagg gtctgggcag cgacgagact 27240
cgggccgcga acgctctgca aggaagcgga gaggagcatg agcaccacag cgccctggtg 27300
gagttggaag gcgacaacgc gcgcctggcg gtgctcaagc gcacggtcga gctgacccac 27360
ttcgcctacc cggcgctcaa cctgcccccc aaggtcatga gcgccgtcat ggaccaggtg 27420
ctcatcaagc gcgcctcgcc cctctcagag gaggagatgc aggaccccga gagctcggac 27480
gagggcaagc ccgtggtcag cgacgagcag ctggcgcgct ggctgggagc gagcagcacc 27540
ccccagagcc tggaagagcg gcgcaagctc atgatggccg tggtcctggt gaccgtggag 27600
ctggagtgtc tgcgccgctt cttcgccgac gcggagaccc tgcgcaaggt cgaggagaac 27660
ctgcactacc tcttcaggca cgggttcgtg cgccaggcct gcaagatctc caacgtggag 27720
ctgaccaacc tggtctccta catgggcatc ctgcacgaga accgcctggg gcagaacgtg 27780
ctgcacacca ccctgcgcgg ggaggcccgc cgcgactaca tccgcgactg cgtctacctg 27840
tacctctgcc acacctggca gacgggcatg ggcgtgtggc agcagtgcct ggaggagcag 27900
aacctgaaag agctctgcaa gctcctgcag aagaacctca aggccctgtg gaccgggttc 27960
gacgagcgca ccaccgcctc ggacctggcc gacctcatct tccccgagcg cctgcggctg 28020
acgctgcgca acgggctgcc cgactttatg agccaaagca tgttgcaaaa ctttcgctct 28080
ttcatcctcg aacgctccgg gatcctgccc gccacctgct ccgcactgcc ctcggacttc 28140
gtgccgctga ccttccgcga gtgccccccg ccgctctgga gccactgcta cttgctgcgc 28200
ctggccaact acctggccta ccactcggac gtgatcgagg acgtcagcag cgagggtctg 28260
ctcgagtgcc actgccgctg caacctctgc acgccgcacc gctccttggc ctgcaacccc 28320
cagctgctga gcgagaccca gatcatcggc accttcgagt tgcaaggccc cggcgagggc 28380
aaggggggtc tcaaactcac cccggggctg tggacctcgg cctacttgcg caagttcgtg 28440
cccgaggact accatccctt cgagatcagg ttctacgagg accaatccca gccgcccaag 28500
gccgagctgt cggcctgcgt catcacccag ggggccatcc tggcccaatt gcaagccatc 28560
cagaaatccc gccaagaatt tctgctgaaa aagggccacg gggtctactt ggacccccag 28620
accggagagg agctcaaccc cagcttcccc caggatgccc cgaggaagca gcaagaagct 28680
gaaagtggag ctgccgctgc cgccggagga tttggaggaa gactgggaga gcagtcaggc 28740
agaggagatg gaagactggg acagcactca ggcagaggag gacagcctgc aagacagtct 28800
ggaggaggaa gacgaggtgg aggaggaggc agaggaagaa gcagccgccg ccagaccgtc 28860
gtcctcggcg gaggagaaag caagcagcac ggataccatc tccgctccgg gtcggggtcg 28920
cggcggccgg gcccacagta gatgggacga gaccgggcgc ttcccgaacc ccaccaccca 28980
gaccggtaag aaggagcggc agggatacaa gtcctggcgg gggcacaaaa acgccatcgt 29040
ctcctgcttg caagcctgcg ggggcaacat ctccttcacc cggcgctacc tgctcttcca 29100
ccgcggggtg aacttccccc gcaacatctt gcattactac cgtcacctcc acagccccta 29160
ctactgtttc caagaagagg cagaaaccca gcagcagcag cagaaaacca gcggcagcag 29220
cagcagctag aaaatccaca gcggcggcag gtggactgag gatcgcggcg aacgagccgg 29280
cgcagacccg ggagctgagg aaccggatct ttcccaccct ctatgccatc ttccagcaga 29340
gtcgggggca ggagcaggaa ctgaaagtca agaaccgttc tctgcgctcg ctcacccgca 29400
gttgtctgta tcacaagagc gaagaccaac ttcagcgcac tctcgaggac gccgaggctc 29460
tcttcaacaa gtactgcgcg ctcactctta aagagtagcc cgcgcccgcc cacacacgga 29520
aaaaggcggg aattacgtca ccacctgcgc ccttcgcccg accatcatca tgagcaaaga 29580
gattcccacg ccttacatgt ggagctacca gccccagatg ggcctggccg ccggcgccgc 29640
ccaggactac tccacccgca tgaactggct cagtgccggg cccgcgatga tctcacgggt 29700
gaatgacatc cgcgcccacc gaaaccagat actcctagaa cagtcagcga tcaccgccac 29760
gccccgccat caccttaatc cgcgtaattg gcccgccgcc ctggtgtacc aggaaattcc 29820
ccagcccacg accgtactac ttccgcgaga cgcccaggcc gaagtccagc tgactaactc 29880
aggtgtccag ctggccggcg gcgccgccct gtgtcgtcac cgccccgctc agggtataaa 29940
gcggctggtg atccgaggca gaggcacaca gctcaacgac gaggtggtga gctcttcgct 30000
gggtctgcga cctgacggag tcttccaact cgccggatcg gggagatctt ccttcacgcc 30060
tcgtcaggcc gtcctgactt tggagagttc gtcctcgcag ccccgctcgg gcggcatcgg 30120
cactctccag ttcgtggagg agttcactcc ctcggtctac ttcaacccct tctccggctc 30180
ccccggccac tacccggacg agttcatccc gaacttcgac gccatcagcg agtcggtgga 30240
cggctacgat tgaatgtccc atggtggcgc ggctgaccta gctcggcttc gacacctgga 30300
ccactgccgc cgcttccgct gcttcgctcg ggatctcgcc gagtttgcct actttgagct 30360
gcccgaggag caccctcagg gcccggccca cggagtgcgg atcgtcgtcg aagggggcct 30420
cgactcccac ctgcttcgga ttttcagcca gcgtccgatc ctggtcgagc gcgagcaagg 30480
acagaccctt ctgaccctgt actgcatctg caaccacccc ggcctgcatg aaagtctttg 30540
ttgtctgctg tgtactgagt ataataaaag ctgagatcag cgactactcc ggactcgatt 30600
gtggtgttcc tgctatcaac cggtccctgt tcttcaccgg gaacgagacc gagctccagc 30660
tccagtgtaa gccccacaag aagtatctca cctggctgtt ccagggctct ccgatcgccg 30720
ttgtcaacca ctgcgacaac gacggagtcc tgctgagcgg ccctgccaac cttacttttt 30780
ccacccgcag aagcaagctc cagctcttcc aacccttcct ccccgggacc tatcagtgcg 30840
tctcgggacc ctgccatcac accttccacc tgatcccgaa taccacagcg ccgctccccg 30900
ctactaacaa ccaaactacc caccaacgcc accgtcgcga cctttctgaa tctaatacta 30960
ccacccacac cggaggtgag ctccgaggtc gaccaacctc tgggatttac tacggggtta 31020
accccttaat taaggggatt ccatatggta cgtacatcgc ctctcctacg agctcctgca 31080
gcagcgccag aagttcacct gcctggtcgg agtcaacccc atcgtcatca cccagcagtc 31140
gggcgatacc aaggggtgca tccactgctc ctgcgactcc cccgactgcg tccacactct 31200
gatcaagacc ctctgcggcc tccgcgacct cctccccatg aactaatcac ccccttatcc 31260
agtgaaataa agatcatatt gatgatgatt ttacagaaat aaagatacaa tcatattgat 31320
gatttgagtt taataaaaaa taaagaatca cttacttgaa atctgatacc aggtctctgt 31380
ccatgttttc tgccaacacc acttcactcc cctcttccca gctctggtac tgcaggcccc 31440
ggcgggctgc aaacttcctc cacacgctga aggggatgtc aaattcctcc tgtccctcaa 31500
tcttcatttt atcttctatc agatgtccaa aaagcgcgtc cgggtggatg atgacttcga 31560
ccccgtctac ccctacgatg cagacaacgc accgaccgtg cccttcatca accccccctt 31620
cgtctcttca gatggattcc aagagaagcc cctgggggtg ctgtccctgc gactggccga 31680
ccccgtcacc accaagaacg gggaaatcac cctcaagctg ggagaggggg tggacctcga 31740
ctcctcggga aaactcatct ccaacacggc caccaaggcc gccgcccctc tcagtttttc 31800
caacaacacc atttccctta acatggatca ccccttttac actaaagatg gaaaattatc 31860
cttacaagtt tctccaccat taaatatact gagaacaagc attctaaaca cactagcttt 31920
aggttttgga tcaggtttag gactccgtgg ctctgccttg gcagtacagt tagtctctcc 31980
acttacattt gatactgatg gaaacataaa gcttacctta gacagaggtt tgcatgttac 32040
aacaggagat gcaattgaaa gcaacataag ctgggctaaa ggtttaaaat ttgaagatgg 32100
agccatagca accaacattg gaaatgggtt agagtttgga agcagtagta cagaaacagg 32160
tgttgatgat gcttacccaa tccaagttaa acttggatct ggccttagct ttgacagtac 32220
aggagccata atggctggta acaaagaaga cgataaactc actttgtgga caacacctga 32280
tccatcgcca aactgtcaaa tactcgcaga aaatgatgca aaactaacac tttgcttgac 32340
taaatgtggt agtcaaatac tggccactgt gtcagtctta gttgtaggaa gtggaaacct 32400
aaaccccatt actggcaccg taagcagtgc tcaggtgttt ctacgttttg atgcaaacgg 32460
tgttctttta acagaacatt ctacactaaa aaaatactgg gggtataggc agggagatag 32520
catagatggc actccatata ccaatgctgt aggattcatg cccaatttaa aagcttatcc 32580
aaagtcacaa agttctacta ctaaaaataa tatagtaggg caagtataca tgaatggaga 32640
tgtttcaaaa cctatgcttc tcactataac cctcaatggt actgatgaca gcaacagtac 32700
atattcaatg tcattttcat acacctggac taatggaagc tatgttggag caacatttgg 32760
ggctaactct tataccttct catacatcgc ccaagaatga acactgtatc ccaccctgca 32820
tgccaaccct tcccacccca ctctgtggaa aaaactctga aacacaaaat aaaataaagt 32880
tcaagtgttt tattgattca acagttttac aggattcgag cagttatttt tcctccaccc 32940
tcccaggaca tggaatacac caccctctcc ccccgcacag ccttgaacat ctgaacgcca 33000
ttggtgatgg acatgctttt ggtctccacg ttccacacag tttcagagcg agccagtctc 33060
gggtcggtca gggagatgaa accctccggg cacaattggg agaagtactc gcctattatc 33120
tggaagaagc agaagagcgg cggtgggaat catagtccgc gaacgggatc ggccggtggt 33180
gtcgcatcag gccccgcagc agtcgctgcc gccgccgctc cgtcaagctg ctgctcaggg 33240
ggtccgggtc cagggactcc ctcagcatga tgcccacggc cctcagcatc agtcgtctgg 33300
tgcggcgggc gcagcagcgc atgcggatct cgctcaggtc gctgcagtac gtgcaacaca 33360
gaaccaccag gttgttcaac agtccatagt tcaacacgct ccagccgaaa ctcatcgcgg 33420
gaaggatgct acccacgtgg ccgtcgtacc agatcctcag gtaaatcaag tggtgccccc 33480
tccagaacac gctgcccacg tacatgatct ccttgggcat gtggcggttc accacctccc 33540
ggtaccacat caccctctgg ttgaacatgc agccccggat gatcctgcgg aaccacaggg 33600
ccagcaccgc cccgcccgcc atgcagcgaa gagaccccgg gtcccggcaa tggcaatgga 33660
ggacccaccg ctcgtacccg tggatcatct gggagctgaa caagtctatg ttggcacagc 33720
acaggcatat gctcatgcat ctcttcagca ctctcaactc ctcgggggtc aaaaccatat 33780
cccagggcac ggggaactct tgcaggacag cgaaccccgc agaacagggc aatcctcgca 33840
cagaacttac attgtgcatg gacagggtat cgcaatcagg cagcaccggg tgatcctcca 33900
ccagagaagc gcgggtctcg gtctcctcac agcgtggtaa gggggccggc cgatacgggt 33960
gatggcggga cgcggctgat cgtgttcgcg accgtgtcat gatgcagttg ctttcggaca 34020
tatttcctga agtcttggcg cgccaaagtc tagacagcgt ccatagctta ccgagcagca 34080
gcagcagcac acaacaggcg caagagtcag agaaaggctg agctctaacc tgtccacccg 34140
ctctctgctc aatatatagc ccagatctac actgacgtaa aggccaaagt ctaaaaatac 34200
ccgccaaata gtcacacacg cccagcacac gcccagaaac cggtgacaca ctcaaaaaaa 34260
tacgcgcact tcctcaaacg cccaaactgc cgtcatttcc gggttcccac gctacgtcat 34320
caaaacacga ctttcaaatt ccgtcgaccg ttaaaaacgt cacccgcccc gcccctaacg 34380
gtcgcccgtc tctcagccaa tcagcgcccc gcatccccaa attcaaacac ctcatttgca 34440
tattaacgcg caccaaaagt ttgaggtata ttattgatga tg 34482
<210> 7
<211> 32223
<212> DNA
<213> Artificial sequence (Artificial sequence)
<400> 7
aaatcatcat caataatata cctcaaactt ttggtgcgcg ttaatatgca aatgaggtgt 60
ttgaatttgg ggatgcgggg cgctgattgg ctgagagacg ggcgaccgtt aggggcgggg 120
cgggtgacgt tttgatgacg tggccgtgag gcggagccgg tttgcaagtt ctcgtgggaa 180
aagtgacgtc aaacgaggtg tggtttgaac acggaaatac tcaattttcc cgcgctctct 240
gacaggaaat gaggtgtttc tgggcggatg caagtgaaaa cgggccattt tcgcgcgaaa 300
actgaatgag gaagtgaaaa tctgagtaat tccgcgttta tggcagggag gagtatttgc 360
cgagggccga gtagactttg accgattacg tgggggtttc gattaccgta tttttcacct 420
aaatttccgc gtacggtgtc aaagtccggt gtttttacgt aggcgtcagc tgatcgccag 480
ggtatttaaa cctgcgctct ctagtcaaga ggccactctt gagtgccagc gagtagagtt 540
ttctcctccg cgccgcgagt cagatctaca ctttgaaagg cgatcgccga tatcatttcc 600
ccgaaaagtg ccacctgacc gtaactataa cggtcctaag gtagcgaaag ctcagatctc 660
ccgatcccct atggtgcact ctcagtacaa tctgctctga tgccgcatag ttaagccagt 720
atctgctccc tgcttgtgtg ttggaggtcg ctgagtagtg cgcgagcaaa atttaagcta 780
caacaaggca aggcttgacc gacaattgca tgaagaatct gcttagggtt aggcgttttg 840
cgctgcttcg cgatgtacgg gccagatata cgcgttgaca ttgattattg actagttatt 900
aatagtaatc aattacgggg tcattagttc atagcccata tatggagttc cgcgttacat 960
aacttacggt aaatggcccg cctggctgac cgcccaacga cccccgccca ttgacgtcaa 1020
taatgacgta tgttcccata gtaacgccaa tagggacttt ccattgacgt caatgggtgg 1080
agtatttacg gtaaactgcc cacttggcag tacatcaagt gtatcatatg ccaagtacgc 1140
cccctattga cgtcaatgac ggtaaatggc ccgcctggca ttatgcccag tacatgacct 1200
tatgggactt tcctacttgg cagtacatct acgtattagt catcgctatt accatggtga 1260
tgcggttttg gcagtacatc aatgggcgtg gatagcggtt tgactcacgg ggatttccaa 1320
gtctccaccc cattgacgtc aatgggagtt tgttttggca ccaaaatcaa cgggactttc 1380
caaaatgtcg taacaactcc gccccattga cgcaaatggg cggtaggcgt gtacggtggg 1440
aggtctatat aagcagagct cgtttagtga accgtcagat cactagaagc tttattgcgg 1500
tagtttatca cagttaaatt gctaacgcag tcagtgcttc tgacacaaca gtctcgaact 1560
taagctgcag aagttggtcg tgaggcactg ggcaggtaag tatcaaggtt acaagacagg 1620
tttaaggaga ccaatagaaa ctgggcttgt cgagacagag aagactcttg cgtttctgat 1680
aggcacctat tggtcttact gacatccact ttgcctttct ctccacaggt gtccactccc 1740
agttcaatta cagctcttaa ggctagagta ctctagcccg ggatccaccg gtcgccacca 1800
tgaagatggc cagctccgat gccaatccct ccgatggctc cacagccaat ttagtgcccg 1860
aagtgaataa cgaggtcatg gccttagagc ccgtggtggg agctgctatc gctgctcccg 1920
ttgctggaca gcagaacgtg attgaccctt ggattaggaa taacttcgtg caagcccccg 1980
gtggcgagtt taccgtcagc cctcgtaacg cccccggtga gattctgtgg agcgctcccc 2040
tcggccccga tctgaatccc tatttaagcc atctggccag aatgtacaac ggatacgctg 2100
gaggcttcga ggtccaagtt attctggccg gcaacgcctt caccgccggc aagatcatct 2160
tcgccgccgt gccccccaac tttcctaccg agggcctcag cccttcccaa gttaccatgt 2220
tccctcacat catcgtggac gtgagacagc tggagcccgt tctgatccct ttacccgatg 2280
ttcgtaacaa cttctaccat tacaaccaga gcaacgaccc caccatcaaa ctgatcgcta 2340
tgctgtatac acctttaaga gccaacaatg ccggcgacga cgtgttcacc gtgagctgta 2400
gagtgctcac tcgtcccagc cccgattttg acttcatttt tttagtcccc cccaccgtgg 2460
aatctcgtac caaacccttc accgtgccta ttctcaccgt ggaggagatg accaattctc 2520
gtttccctat ccctttagag aaactgttta ccggcccctc cggcgctttc gtggtgcaac 2580
ctcagaacgg tcgttgtacc acagacggcg tgctgctggg cacaacccag ctgtcccccg 2640
tgaacatctg tacctttcgt ggagacgtga cccacatcgc tggcacccaa gaatatacca 2700
tgaatttagc cagccagaac tggaacaact atgaccccac cgaagagatc cccgctcctc 2760
tgggaacccc cgacttcgtc ggaaagattc aaggtgtgct gacacagacc accagaggcg 2820
atggaagcac tcgtggacat aaggctacag tcagcaccgg cagcgtgcac tttacaccca 2880
aactgggcag cgtgcaattc agcacagaca ccagcaacga cttcgagact ggtcagaata 2940
ccaagttcac ccccgtgggc gtggtgcaag atggaagcac cacccaccag aacgagcccc 3000
agcagtgggt tttacccgat tactccggtc gtgactccca taacgtccac ctcgcccccg 3060
ctgtggctcc cacattcccc ggtgagcagc tgctcttttt cagaagcacc atgcccggat 3120
gcagcggcta ccccaacatg aatctcgact gtttactgcc tcaagaatgg gtgcagcact 3180
tctaccaaga agctgccccc gctcagtccg atgtcgcttt attacgtttc gtgaaccccg 3240
ataccggaag ggttttattt gagtgcaagc tgcataagag cggatatgtg acagtggctc 3300
acaccggcca gcacgattta gtgatccccc ccaatggcta ctttcgtttc gactcttggg 3360
tgaatcagtt ctacacactg gcccccatgg gcaacggaac cggaagaaga agagctctct 3420
gaagcggccg ccactgtgct ggatgatccg agctcggtac ctctagagtc gacccgggcg 3480
gccaaaccgc tgatcagcct cgactgtgcc ttctagttgc cagccatctg ttgtttgccc 3540
ctcccccgtg ccttccttga ccctggaagg tgccactccc actgtccttt cctaataaaa 3600
tgaggaaatt gcatcgcatt gtctgagtag gtgtcattct attctggggg gtggggtggg 3660
gcaggacagc aagggggagg attgggaaga caatagcagg catgctgggg atgcggtggg 3720
ctctatggct tctgaggcgg aaagaaccag cagatctgca gatctgaatt catctatgtc 3780
gggtgcggag aaagaggtaa tgaaatggca ttatgggtat tatgggtctg cattaatgaa 3840
tcggccagat atcgacatat gctggccacc gtacatgtgg cttcccatgc tcgcaagccc 3900
tggcccgagt tcgagcacaa tgtcatgacc aggtgcaata tgcatctggg gtcccggcga 3960
tcgcccgagg catgttcatg ccctaccagt gcaacatgca atttgtgaag gtgctgctgg 4020
agcccgatgc catgtccaga gtgagcctga cgggggtgtt tgacatgaat gtggagctgt 4080
ggaaaattct gagatatgat gaatccaaga ccaggtgccg ggcctgcgaa tgcggaggca 4140
agcacgccag gcttcagccc gtgtgtgtgg aggtgacgga ggacctgcga cccgatcatt 4200
tggtgttgtc ctgcaacggg acggagttcg gctccagcgg ggaagaatct gactagagtg 4260
agtagtgttt gggggtgggt gggagcctgc atgatgggca gaatgactaa aatctgtgtt 4320
tttctgtgtg ttgcagcagc atgagcggaa gcgcctcctt tgagggaggg gtattcagcc 4380
cttatctgac ggggcgtctc ccctcctggg cgggagtgcg tcagaatgtg atgggatcca 4440
cggtggacgg ccggcccgtg cagcccgcga actcttcaac cctgacctac gcgaccctga 4500
gctcctcgtc cgtggacgca gctgccgccg cagctgctgc ttccgccgcc agcgccgtgc 4560
gcggaatggc cctgggcgcc ggctactaca gctctctggt ggccaactcg agttccacca 4620
ataatcccgc cagcctgaac gaggagaagc tgttgctgct gatggcccag ctcgaggccc 4680
tgacccagcg cctgggcgag ctgacccagc aggtggctca gctgcaggcg gagacgcggg 4740
ccgcggttgc cacggtgaaa accaaataaa aaatgaatca ataaataaac ggagacggtt 4800
gttgatttta acacagagtc ttgaatcttt atttgatttt tcgcgcgcgg taggccctgg 4860
accaccggtc tcgatcattg agcacccggt ggatcttttc caggacccgg tagaggtggg 4920
cttggatgtt gaggtacatg ggcatgagcc cgtcccgggg gtggaggtag ctccattgca 4980
gggcctcgtg ctcgggggtg gtgttgtaaa tcacccagtc atagcagggg cgcagggcgt 5040
ggtgctgcac gatgtctttg aggaggagac tgatggccac gggcagcccc ttggtgtagg 5100
tgttgacgaa cctattgagc tgggagggat gcatgcgggg ggagatgaga tgcatcttgg 5160
cctggatctt gagattggcg atgttcccgc ccagatcccg ccgggggttc atgttgtgca 5220
ggaccaccag cacggtgtat ccggtgcact tggggaattt gtcatgcaac ttggaaggga 5280
aggcgtgaaa gaatttggag acgcccttgt gaccgcccag gttttccatg cactcatcca 5340
tgatgatggc gatgggcccg tgggcggcgg cctgggcaaa gacgtttcgg gggtcggaca 5400
catcgtagtt gtggtcctgg gtgagctcgt cataggccat tttaatgaat ttggggcgga 5460
gggtacccga ctgggggaca aaggtgccct cgatcccggg ggcgtagttc ccctcgcaga 5520
tctgcatctc ccaggccttg agctcggagg gggggatcat gtccacctgc ggggcgatga 5580
aaaaaacggt ttccggggcg ggggagatga gctgcgccga aagcaggttc cggagcagct 5640
gggacttgcc gcagccggtg gggccgtaga tgaccccgat gaccggctgc aggtggtagt 5700
tgagggagag acagctgccg tcctcgcgga ggaggggggc cacctcgttc atcatctcgc 5760
gcacatgcat gttctcgcgc acgagttccg ccaggaggcg ctcgcccccc agcgagagga 5820
gctcttgcag cgaggcgaag tttttcagcg gcttgagccc gtcggccatg ggcattttgg 5880
agagggtctg ttgcaagagt tccagacggt cccagagctc ggtgatgtgc tctagggcat 5940
ctcgatccag cagacctcct cgtttcgcgg gttggggcga ctgcgggagt agggcaccag 6000
gcgatgggcg tccagcgagg ccagggtccg gtccttccag ggtcgcaggg tccgcgtcag 6060
cgtggtctcc gtcacggtga aggggtgcgc gccgggctgg gcgcttgcga gggtgcgctt 6120
caggctcatc cggctggtcg agaaccgctc ccggtcggcg ccctgcgcgt cggccaggta 6180
gcaattgagc atgagttcgt agttgagcgc ctcggccgcg tggcccttgg cgcggagctt 6240
acctttggaa gtgtgtccgc agacgggaca gaggagggac ttgagggcgt agagcttggg 6300
ggcgaggaag acggactcgg gggcgtaggc gtccgcgccg cagctggcgc agacggtctc 6360
gcactccacg agccaggtga ggtcggggcg gtcggggtca aaaacgaggt ttcctccgtg 6420
ctttttgatg cgtttcttac ctctggtctc catgagctcg tgtccccgct gggtgacaaa 6480
gaggctgtcc gtgtccccgt agaccgactt tatgggccgg tcctcgagcg gggtgccgcg 6540
gtcctcgtcg tagaggaacc ccgcccactc cgagacgaag gcccgggtcc aggccagcac 6600
gaaggaggcc acgtgggagg ggtagcggtc gttgtccacc agcgggtcca ccttctccag 6660
ggtatgcaag cacatgtccc cctcgtccac atccaggaag gtgattggct tgtaagtgta 6720
ggccacgtga ccgggggtcc cggccggggg ggtataaaag ggggcgggcc cctgctcgtc 6780
ctcactgtct tccggatcgc tgtccaggag cgccagctgt tggggtaggt attccctctc 6840
gaaggcgggc atgacctcgg cactcaggtt gtcagtttct agaaacgagg aggatttgat 6900
attgacggtg ccgttggaga cgcctttcat gagcccctcg tccatctggt cagaaaagac 6960
gatctttttg ttgtcgagct tggtggcgaa ggagccgtag agggcgttgg agagcagctt 7020
ggcgatggag cgcatggtct ggttcttttc cttgtcggcg cgctccttgg cggcgatgtt 7080
gagctgcacg tactcgcgcg ccacgcactt ccattcgggg aagacggtgg tgagctcgtc 7140
gggcacgatt ctgacccgcc agccgcggtt gtgcagggtg atgaggtcca cgctggtggc 7200
cacctcgccg cgcaggggct cgttggtcca gcagaggcgc ccgcccttgc gcgagcagaa 7260
ggggggcagc gggtccagca tgagctcgtc gggggggtcg gcgtccacgg tgaagatgcc 7320
gggcaggagc tcggggtcga agtagctgat gcaggtgccc agatcgtcca gacttgcttg 7380
ccagtcgcgc acggccagcg cgcgctcgta ggggctgagg ggcgtgcccc agggcatggg 7440
gtgcgtgagc gcggaggcgt acatgccgca gatgtcgtag acgtagaggg gctcctggag 7500
gacgccgatg taggtggggt agcagcgccc cccgcggatg ctggcgcgca cgtagtcgta 7560
cagctcgtgc gagggcgcga ggagccccgt gccgagattg gagcgctgcg gcttttcggc 7620
gcggtagacg atctggcgga agatggcgtg ggagttggag gagatggtgg gcctctggaa 7680
gatgttgaag tgggcatggg gcagtccgac cgagtccctg atgaagtggg cgtaggagtc 7740
ctgcagcttg gcgacgagct cggcggtgac gaggacgtcc agggcgcagt agtcgagggt 7800
ctcttggatg atgtcgtact tgagctggcc cttctgcttc cacagctcgc ggttgagaag 7860
gaactcttcg cggtccttcc agtactcttc gagggggaac ccgtcctgat cggcacggta 7920
agagcccacc atgtagaact ggttgacggc cttgtaggcg cagcagccct tctccacggg 7980
gagggcgtaa gcttgcgcgg ccttgcgcag ggaggtgtgg gtgagggcga aggtgtcgcg 8040
caccatgact ttgaggaact ggtgcttgaa gtcgaggtcg tcgcagccgc cctgctccca 8100
gagctggaag tccgtgcgct tcttgtaggc ggggttgggc aaagcgaaag taacatcgtt 8160
gaagaggatc ttgcccgcgc ggggcatgaa gttgcgagtg atgcggaaag gctggggcac 8220
ctcggcccgg ttgttgatga cctgggcggc gaggacgatc tcgtcgaagc cgttgatgtt 8280
gtgcccgacg atgtagagtt ccacgaatcg cgggcggccc ttgacgtggg gcagcttctt 8340
gagctcgtcg taggtgagct cggcggggtc gctgagcccg tgctgctcga gggcccagtc 8400
ggcgacgtgg gggttggcgc tgaggaagga agtccagaga tccacggcca gggcggtctg 8460
caagcggtcc cggtactgac ggaactgctg gcccacggcc attttttcgg gggtgacgca 8520
gtagaaggtg cgggggtcgc cgtgccagcg gtcccacttg agctggaggg cgaggtcgtg 8580
ggcgagctcg acgagcggcg ggtccccgga gagtttcatg accagcatga aggggacgag 8640
ctgcttgccg aaggacccca tccaggtgta ggtttccaca tcgtaggtga ggaagagcct 8700
ttcggtgcga ggatgcgagc cgatggggaa gaactggatc tcctgccacc agttggagga 8760
atggctgttg atgtgatgga agtagaaatg ccgacggcgc gccgagcact cgtgcttgtg 8820
tttatacaag cgtccgcagt gctcgcaacg ctgcacggga tgcacgtgct gcacgagctg 8880
tacctgggtt cctttgacga ggaatttcag tgggcagtgg agcgctggcg gctgcatctg 8940
gtgctgtact acgtcctggc catcggcgtg gccatcgtct gcctcgatgg tggtcatgct 9000
gacgagcccg cgcgggaggc aggtccagac ctcggctcgg acgggtcgga gagcgaggac 9060
gagggcgcgc aggccggagc tgtccagggt cctgagacgc tgcggagtca ggtcagtggg 9120
cagcggcggc gcgcggttga cttgcaggag cttttccagg gcgcgcggga ggtccagatg 9180
gtacttgatc tccacggcgc cgttggtggc gacgtccacg gcttgcaggg tcccgtgccc 9240
ctggggcgcc accaccgtgc cccgtttctt cttgggcggc ggcggctcca tgcttagaag 9300
cggcggcgag gacgcgcgcc gggcggcagg ggcggctcgg ggcccggagg caggggcggc 9360
aggggcacgt cggcgccgcg cgcgggcagg ttctggtact gcgcccggag aagactggcg 9420
tgagcgacga cgcgacggtt gacgtcctgg atctgacgcc tctgggtgaa ggccacggga 9480
cccgtgagtt tgaacctgaa agagagttcg acagaatcaa tctcggtatc gttgacggcg 9540
gcctgccgca ggatctcttg cacgtcgccc gagttgtcct ggtaggcgat ctcggtcatg 9600
aactgctcga tctcctcctc ctgaaggtct ccgcggccgg cgcgctcgac ggtggccgcg 9660
aggtcgttgg agatgcggcc catgagctgc gagaaggcgt tcatgccggc ctcgttccag 9720
acgcggctgt agaccacggc tccgtcgggg tcgcgcgcgc gcatgaccac ctgggcgagg 9780
ttgagctcga cgtggcgcgt gaagaccgcg tagttgcaga ggcgctggta gaggtagttg 9840
agcgtggtgg cgatgtgctc ggtgacgaag aagtacatga tccagcggcg gagcggcatc 9900
tcgctgacgt cgcccagggc ttccaagcgc tccatggcct cgtagaagtc cacggcgaag 9960
ttgaaaaact gggagttgcg cgccgagacg gtcaactcct cctccagaag acggatgagc 10020
tcggcgatgg tggcgcgcac ctcgcgctcg aaggccccgg ggggctcctc ttccatttcc 10080
tcctcttcct cctccactaa catctcttct acttcctcct caggaggcgg cggcggggga 10140
ggggccctgc gtcgccggcg gcgcacgggc agacggtcga tgaagcgctc gatggtctcc 10200
ccgcgccggc gacgcatggt ctcggtgacg gcgcgcccgt cctcgcgggg ccgcagcgtg 10260
aagacgccgc cgcgcatctc caggtggccg ccgggggggt ctccgttggg cagggagagg 10320
gcgctgacga tgcatcttat caattgaccc gtagggactc cgcgcaagga cctgagcgtc 10380
tcgagatcca cgggatccga aaaccgctga acgaaggctt cgagccagtc gcagtcgcaa 10440
ggtaggctga gcccggtttc ttgttcttcg ggtatttggt cgggaggcgg gcgggcgatg 10500
ctgctggtga tgaagttgaa gtaggcggtc ctgagacggc ggatggtggc gaggagcacc 10560
aggtccttgg gcccggcttg ctggatgcgc agacggtcgg ccatgcccca ggcgtggtcc 10620
tgacacctgg cgaggtcctt gtagtagtcc tgcatgagcc gctccacggg cacctcctcc 10680
tcgcccgcgc ggccgtgcat gcgcgtgagc ccgaacccgc gctgcggctg gacgagcgcc 10740
aggtcggcga cgacgcgctc ggcgaggatg gcctgctgga tctgggtgag ggtggtctgg 10800
aagtcgtcga agtcgacgaa gcggtggtag gctccggtgt tgatggtgta ggagcagttg 10860
gccatgacgg accagttgac ggtctggtgg ccggggcgca cgagctcgtg gtacttgagg 10920
cgcgagtagg cgcgcgtgtc gaagatgtag tcgttgcagg tgcgcacgag gtactggtat 10980
ccgacgagga agtgcggcgg cggctggcgg tagagcggcc atcgctcggt ggcgggggcg 11040
ccgggcgcga ggtcctcgag catgaggcgg tggtagccgt agatgtacct ggacatccag 11100
gtgatgccgg cggcggtggt ggaggcgcgc gggaactcgc ggacgcggtt ccagatgttg 11160
cgcagcggca ggaagtagtt catggtggcc gcggtctggc ccgtgaggcg cgcgcagtcg 11220
tggatgctct agacatacgg gcaaaaacga aagcggtcag cggctcgact ccgtggcctg 11280
gaggctaagc gaacgggttg ggctgcgcgt gtaccccggt tcgaatctcg aatcaggctg 11340
gagccgcagc taacgtggta ctggcactcc cgtctcgacc caagcctgct aacgaaacct 11400
ccaggatacg gaggcgggtc gttttttggc cttggtcgct ggtcatgaaa aactagtaag 11460
cgcggaaagc ggccgcccgc gatggctcgc tgccgtagtc tggagaaaga atcgccaggg 11520
ttgcgttgcg gtgtgccccg gttcgagcct cagcgctcgg cgccggccgg attccgcggc 11580
taacgtgggc gtggctgccc cgtcgtttcc aagacccctt agccagccga cttctccagt 11640
tacggagcga gcccctcttt ttttcttgtg tttttgccag atgcatcccg tactgcggca 11700
gatgcgcccc caccctccac cacaaccgcc cctaccgcag cagcagcaac agccggcgct 11760
tctgcccccg ccccagcagc agcagccagc cactaccgcg gcggccgccg tgagcggagc 11820
cggcgttcag tatgacctgg ccttggaaga gggcgagggg ctggcgcggc tgggggcgtc 11880
gtcgccggag cggcacccgc gcgtgcagat gaaaagggac gctcgcgagg cctacgtgcc 11940
caagcagaac ctgttcagag acaggagcgg cgaggagccc gaggagatgc gcgcctcccg 12000
cttccacgcg gggcgggagc tgcggcgcgg cctggaccga aagcgggtgc tgagggacga 12060
ggatttcgag gcggacgagc tgacggggat cagccccgcg cgcgcgcacg tggccgcggc 12120
caacctggtc acggcgtacg agcagaccgt gaaggaggag agcaacttcc aaaaatcctt 12180
caacaaccac gtgcgcacgc tgatcgcgcg cgaggaggtg accctgggcc tgatgcacct 12240
gtgggacctg ctggaggcca tcgtgcagaa ccccacgagc aagccgctga cggcgcagct 12300
gtttctggtg gtgcagcaca gtcgggacaa cgagacgttc agggaggcgc tgctgaatat 12360
caccgagccc gagggccgct ggctcctgga cctggtgaac attctgcaga gcatcgtggt 12420
gcaggagcgc gggctgccgc tgtccgagaa gctggcggcc atcaacttct cggtgctgag 12480
cctgggcaag tactacgcta ggaagatcta caagaccccg tacgtgccca tagacaagga 12540
ggtgaagatc gatgggtttt acatgcgcat gaccctgaaa gtgctgaccc tgagcgacga 12600
tctgggggtg taccgcaacg acaggatgca ccgcgcggtg agcgccagcc gccggcgcga 12660
gctgagcgac caggagctga tgcacagcct gcagcgggcc ctgaccgggg ccgggaccga 12720
gggggagagc tactttgaca tgggcgcgga cctgcgctgg cagcccagcc gccgggcctt 12780
ggaagctgcc ggcggcgtgc cctacgtgga ggaggtggac gatgaggagg aggagggcga 12840
gtacctggaa gactgatggc gcgaccgtat ttttgctaga tgcagcaaca gccaccgccg 12900
ccgcctcctg atcccgcgat gcgggcggcg ctgcagagcc agccgtccgg cattaactcc 12960
tcggacgatt ggacccaggc catgcaacgc atcatggcgc tgacgacccg caatcccgaa 13020
gcctttagac agcagcctca ggccaaccgg ctctcggcca tcctggaggc cgtggtgccc 13080
tcgcgctcga accccacgca cgagaaggtg ctggccatcg tgaacgcgct ggtggagaac 13140
aaggccatcc gcggcgacga ggccgggctg gtgtacaacg cgctgctgga gcgcgtggcc 13200
cgctacaaca gcaccaacgt gcagacgaac ctggaccgca tggtgaccga cgtgcgcgag 13260
gcggtgtcgc agcgcgagcg gttccaccgc gagtcgaacc tgggctccat ggtggcgctg 13320
aacgccttcc tgagcacgca gcccgccaac gtgccccggg gccaggagga ctacaccaac 13380
ttcatcagcg cgctgcggct gatggtggcc gaggtgcccc agagcgaggt gtaccagtcg 13440
gggccggact acttcttcca gaccagtcgc cagggcttgc agaccgtgaa cctgagccag 13500
gctttcaaga acttgcaggg actgtggggc gtgcaggccc cggtcgggga ccgcgcgacg 13560
gtgtcgagcc tgctgacgcc gaactcgcgc ctgctgctgc tgctggtggc gcccttcacg 13620
gacagcggca gcgtgagccg cgactcgtac ctgggctacc tgcttaacct gtaccgcgag 13680
gccatcgggc aggcgcacgt ggacgagcag acctaccagg agatcaccca cgtgagccgc 13740
gcgctgggcc aggaggaccc gggcaacctg gaggccaccc tgaacttcct gctgaccaac 13800
cggtcgcaga agatcccgcc ccagtacgcg ctgagcaccg aggaggagcg catcctgcgc 13860
tacgtgcagc agagcgtggg gctgttcttg atgcaggagg gggccacgcc cagcgccgcg 13920
ctcgacatga ccgcgcgcaa catggagccc agcatgtacg cccgcaaccg cccgttcatc 13980
aataagctga tggactactt gcatcgggcg gccgccatga actcggacta ctttaccaac 14040
gccatcttga acccgcactg gctcccgccg cccgggttct acacgggcga gtacgacatg 14100
cccgacccca acgacgggtt cctgtgggac gacgtggaca gcagcgtgtt ctcgccgcgg 14160
cccaccacca ccaccgtgtg gaagaaagag ggcggggacc ggcggccgtc ctcggcgctg 14220
tccggtcgcg cgggtgctgc cgcggcggtg cccgaggctg ccagcccctt cccgagcctg 14280
cccttttcgc tgaacagcgt gcgcagcagc gagctgggtc ggctgacgcg gccgcgcctg 14340
ctgggcgagg aggagtacct gaacgactcc ttgttgaagc ccgagcgcga gaagaacttc 14400
cccaataacg ggatagagag cctggtggac aagatgagcc gctggaagac gtacgcgcac 14460
gagcacaggg acgagccccg agctagcagc gcaggcaccc gtagacgcca gcggcacgac 14520
aggcagcggg gactggtgtg ggacgatgag gattccgccg acgacagcag cgtgttggac 14580
ttgggtggga gtggtggtgg taacccgttc gctcacctgc gcccccgtat cgggcgcctg 14640
atgtaagaat ctgaaaaaat aaaagacggt actcaccaag gccatggcga ccagcgtgcg 14700
ttcttctctg ttgtttgtag tagtatgatg aggcgcgtgt acccggaggg tcctcctccc 14760
tcgtacgaga gcgtgatgca gcaggcggtg gcggcggcga tgcagccccc gctggaggcg 14820
ccttacgtgc ccccgcggta cctggcgcct acggaggggc ggaacagcat tcgttactcg 14880
gagctggcac ccttgtacga taccacccgg ttgtacctgg tggacaacaa gtcggcggac 14940
atcgcctcgc tgaactacca gaacgaccac agcaacttcc tgaccaccgt ggtgcagaac 15000
aacgatttca cccccacgga ggccagcacc cagaccatca actttgacga gcgctcgcgg 15060
tggggcggcc agctgaaaac catcatgcac accaacatgc ccaacgtgaa cgagttcatg 15120
tacagcaaca agttcaaggc gcgggtgatg gtctcgcgca agacccccaa cggggtcacg 15180
gtaggggatg attatgatgg tagtcaggac gagctgacct acgagtgggt ggagtttgag 15240
ctgcccgagg gcaacttctc ggtgaccatg accatcgatc tgatgaacaa cgccatcatc 15300
gacaactact tggcggtggg gcggcagaac ggggtgctgg agagcgacat cggcgtgaag 15360
ttcgacacgc gcaacttccg gctgggctgg gaccccgtga ccgagctggt gatgccgggc 15420
gtgtacacca acgaggcctt ccaccccgac atcgtcctgc tgcccggctg cggcgtggac 15480
ttcaccgaga gccgcctcag caacctgctg ggcatccgca agcggcagcc cttccaggag 15540
ggcttccaga tcctgtacga ggacctggag gggggcaaca tccccgcgct cttggatgtc 15600
gaagcctatg aagaaagtaa ggaaaaagca gaggctgagg caactacagc cgtggctacc 15660
gccgcgactg tggcagatgc cactgtcacc aggggcgata cattcgccac ccaggcggag 15720
gaagcagccg ccctagcggc gaccgatgat agtgaaagta agatagtcat caagccggtg 15780
gagaaggaca gcaagaacag gagctacaac gttctaccgg atggaaagaa caccgcctac 15840
cgcagctggt acctggccta caactacggc gaccccgaga agggcgtgcg ctcctggacg 15900
ctgctcacca cctcggacgt cacctgcggc gtggagcaag tctactggtc gctgcccgac 15960
atgatgcaag acccggtcac cttccgctcc acgcgacaag ttagcaacta cccggtggtg 16020
ggcgccgagc tcctgcccgt ctactccaag agcttcttca acgagcaggc cgtctactcg 16080
cagcagctgc gtgccttcac ctcgctcacg cacgtcttca accgcttccc cgagaaccag 16140
atcctcgtcc gcccgcccgc gcccaccatt accaccgtca gtgaaaacgt tcctgctctc 16200
acagatcacg ggaccctgcc gctgcgcagc agtatccggg gagtccagcg cgtgaccgtc 16260
actgacgcca gacgccgcac ctgcccctac gtctacaagg ccctgggcgt agtcgcgccg 16320
cgcgtcctct cgagccgcac cttctaaaaa atgtccattc tcatctcgcc cagtaataac 16380
accggttggg gcctgcgcgc gcccagcaag atgtacggag gcgctcgcca acgctccacg 16440
caacaccccg tgcgcgtgcg cgggcacttc cgcgctccct ggggcgccct caagggccgc 16500
gtgcgctcgc gcaccaccgt cgacgacgtg atcgaccagg tggtggccga cgcgcgcaac 16560
tacacgcccg ccgccgcgcc cgcctccacc gtggacgccg tcatcgacag cgtggtggcc 16620
gacgcgcgcc ggtacgcccg cgccaagagc cggcggcggc gcatcgcccg gcggcaccgg 16680
agcacccccg ccatgcgcgc ggcgcgagcc ttgctgcgca gggccaggcg cacgggacgc 16740
agggccatgc tcagggcggc cagacgcgcg gcctccggca gcagcagcgc cggcaggacc 16800
cgcagacgcg cggccacggc ggcggcggcg gccatcgcca gcatgtcccg cccgcggcgc 16860
ggcaacgtgt actgggtgcg cgacgccgcc accggtgtgc gcgtgcccgt gcgcacccgc 16920
ccccctcgca cttgaagatg ctgacttcgc gatgttgatg tgtcccagcg gcgaggagga 16980
tgtccaagcg caaatacaag gaagagatgc tccaggtcat cgcgcctgag atctacggcc 17040
ccgcggcggc ggtgaaggag gaaagaaagc cccgcaaact gaagcgggtc aaaaaggaca 17100
aaaaggagga ggaagatgac ggactggtgg agtttgtgcg cgagttcgcc ccccggcggc 17160
gcgtgcagtg gcgcgggcgg aaagtgaaac cggtgctgcg gcccggcacc acggtggtct 17220
tcacgcccgg cgagcgttcc ggctccgcct ccaagcgctc ctacgacgag gtgtacgggg 17280
acgaggacat cctcgagcag gcggtcgagc gtctgggcga gtttgcttac ggcaagcgca 17340
gccgccccgc gcccttgaaa gaggaggcgg tgtccatccc gctggaccac ggcaacccca 17400
cgccgagcct gaagccggtg accctgcagc aggtgctgcc gagcgcggcg ccgcgccggg 17460
gcttcaagcg cgagggcggc gaggatctgt acccgaccat gcagctgatg gtgcccaagc 17520
gccagaagct ggaggacgtg ctggagcaca tgaaggtgga ccccgaggtg cagcccgagg 17580
tcaaggtgcg gcccatcaag caggtggccc cgggcctggg cgtgcagacc gtggacatca 17640
agatccccac ggagcccatg gaaacgcaga ccgagcccgt gaagcccagc accagcacca 17700
tggaggtgca gacggatccc tggatgccag cggcttccac caccaccact cgccgaagac 17760
gcaagtacgg cgcggccagc ctgctgatgc ccaactacgc gctgcatcct tccatcatcc 17820
ccacgccggg ctaccgcggc acgcgcttct accgcggcta caccagcagc cgccgccgca 17880
agaccaccac ccgccgccgt cgtcgcagcc gccgcagcag caccgcgact tccgccttgg 17940
tgcggagagt gtatcgcagc gggcgcgagc ctctgaccct gccgcgcgcg cgctaccacc 18000
cgagcatcgc catttaacta ccgcctccta cttgcagata tggccctcac atgccgcctc 18060
cgcgtcccca ttacgggcta ccgaggaaga aagccgcgcc gtagaaggct gacggggaac 18120
gggctgcgtc gccatcacca ccggcggcgg cgcgccatca gcaagcggtt ggggggaggc 18180
ttcctgcccg cgctgatccc catcatcgcc gcggcgatcg gggcgatccc cggcatagct 18240
tccgtggcgg tgcaggcctc tcagcgccac tgagacacaa aaaagcatgg atttgtaata 18300
aaaaaatgga ctgacgctcc tggtcctgtg atgtgtgttt ttagatggaa gacatcaatt 18360
tttcgtccct ggcaccgcga cacggcacgc ggccgtttat gggcacctgg agcgacatcg 18420
gcaacagcca actgaacggg ggcgccttca attggagcag tctctggagc gggcttaaga 18480
atttcgggtc cacgctcaaa acctatggca acaaggcgtg gaacagcagc acagggcagg 18540
cgctgaggga aaagctgaaa gagcagaact tccagcagaa ggtggtcgat ggcctggcct 18600
cgggcatcaa cggggtggtg gacctggcca accaggccgt gcagaaacag atcaacagcc 18660
gcctggacgc ggtcccgccc gcggggtccg tggagatgcc ccaggtggag gaggagctgc 18720
ctcccctgga caagcgcggc gacaagcgac cgcgtcccga cgcggaggag acgctgctga 18780
cgcacacgga cgagccgccc ccgtacgagg aggcggtgaa actgggtctg cccaccacgc 18840
ggcccgtggc gcctctggcc accggggtgc tgaaacccag cagcagcagc cagcccgcga 18900
ccctggactt gcctccgcct gcttcccgcc cctccacagt ggctaagccc ctgccgccgg 18960
tggccgtcgc gtcgcgcgcc ccccgaggcc gcccccaggc gaactggcag agcactctga 19020
acagcatcgt gggtctggga gtgcagagtg tgaagcgccg ccgctgctat taaaagacac 19080
tgtagcgctt aacttgcttg tctgtgtgtg tatatgtatg tccgccgacc agaaggagga 19140
agaggcgcgt cgccgagttg caagatggcc accccatcga tgctgcccca gtgggcgtac 19200
atgcacatcg ccggacagga cgcttcggag tacctgagtc cgggtctggt gcagttcgcc 19260
cgcgccacag acacctactt cagtctgggg aacaagttta ggaaccccac ggtggcgccc 19320
acgcacgatg tgaccaccga ccgcagccag cggctgacgc tgcgcttcgt gcccgtggac 19380
cgcgaggaca acacctactc gtacaaagtg cgctacacgc tggccgtggg cgacaaccgc 19440
gtgctggaca tggccagcac ctactttgac atccgcggcg tgctggatcg gggccccagc 19500
ttcaaaccct actccggcac cgcctacaac agcctagctc ccaagggagc gcccaacacc 19560
tcacagtgga aggattccga cagcaaaatg catacttttg gagttgctgc catgcccggt 19620
gttgttggta aaaaaataga agccgatggt ctgcctattg gaatagattc atcctctgga 19680
actgacacca taatttatgc tgataaaact ttccaaccag agccacaggt tggaagtgac 19740
agttgggtcg acaccaatgg tgcagaggaa aaatatggag gtagagctct taaggacact 19800
acaaacatga agccctgcta cggttctttt gccaggccta ccaacaaaga aggtggacag 19860
gctaacataa aagattctga aactgccagc actactccta actatgatat agatttggca 19920
ttctttgaca gcaaaaatat tgcagctaac tacgatccag atattgtaat gtacacagaa 19980
aatgttgagt tgcaaactcc agatactcat attgtgttta agccaggaac ttcagatgaa 20040
agttcagaag ccaatttggg ccagcaggcc atgcccaaca gacccaacta catcgggttc 20100
agagacaact ttatcgggct catgtactac aacagcactg gcaatatggg tgtactggct 20160
ggtcaggcct cccagctaaa tgctgtggtg gacttgcagg acagaaacac cgaactgtcc 20220
taccagctct tgcttgactc tctgggtgac agaaccaggt atttcagtat gtggaatcag 20280
gcggtggaca gctatgaccc cgatgtgcgc attattgaaa atcacggtgt ggaggatgaa 20340
ctccccaatt attgcttccc tttgaatggt gtaggcttta cagatactta ccagggtgtt 20400
aaagttaaga cagatacagc cgctactggt accaatggaa cgcagtggga caaagatgat 20460
accacagtca gcactgccaa tgagatccac tcaggcaatc ctttcgccat ggagatcaac 20520
atccaggcca acctgtggcg gaacttcctc tacgcgaacg tggcgctgta cctgcccgac 20580
tcctacaagt acacgccggc caacatcacg ctgccgacca acaccaacac ctacgattac 20640
atgaacggcc gcgtggtggc gccctcgctg gtggacgcct acatcaacat cggggcgcgc 20700
tggtcgctgg accccatgga caacgtcaac cccttcaacc accaccgcaa cgcgggcctg 20760
cgctaccgct ccatgctcct gggcaacggg cgctacgtgc ccttccacat ccaggtgccc 20820
caaaagtttt tcgccatcaa gagcctcctg ctcctgcccg ggtcctacac ctacgagtgg 20880
aacttccgca aggacgtcaa catgatcctg cagagctccc tcggcaacga cctgcgcacg 20940
gacggggcct ccatcgcctt caccagcatc aacctctacg ccaccttctt ccccatggcg 21000
cacaacaccg cctccacgct cgaggccatg ctgcgcaacg acaccaacga ccagtccttc 21060
aacgactacc tctcggcggc caacatgctc taccccatcc cggccaacgc caccaacgtg 21120
cccatctcca tcccctcgcg caactgggcc gccttccgcg gatggtcctt cacgcgcctc 21180
aagacccgcg agacgccctc gctcggctcc gggttcgacc cctacttcgt ctactcgggc 21240
tccatcccct acctcgacgg caccttctac ctcaaccaca ccttcaagaa ggtctccatc 21300
accttcgact cctccgtcag ctggcccggc aacgaccgcc tcctgacgcc caacgagttc 21360
gaaatcaagc gcaccgtcga cggagaggga tacaacgtgg cccagtgcaa catgaccaag 21420
gactggttcc tggtccagat gctggcccac tacaacatcg gctaccaggg cttctacgtg 21480
cccgagggct acaaggaccg catgtactcc ttcttccgca acttccagcc catgagccgc 21540
caggtcgtgg acgaggtcaa ctacaaggac taccaggccg tcaccctggc ctaccagcac 21600
aacaactcgg gcttcgtcgg ctacctcgcg cccaccatgc gccagggcca gccctacccc 21660
gccaactacc cctacccgct catcggcaag agcgccgtcg ccagcgtcac ccagaaaaag 21720
ttcctctgcg accgggtcat gtggcgcatc cccttctcca gcaacttcat gtccatgggc 21780
gcgctcaccg acctcggcca gaacatgctc tacgccaact ccgcccacgc gctagacatg 21840
aatttcgaag tcgaccccat ggatgagtcc acccttctct atgttgtctt cgaagtcttc 21900
gacgtcgtcc gagtgcacca gccccaccgc ggcgtcatcg aggccgtcta cctgcgcacg 21960
cccttctcgg ccggcaacgc caccacctaa agccccgctc ttgcttcttg caagatgacg 22020
gcctgtggct ccggcgagca ggagctcagg gccatcctcc gcgacctggg ctgcgggccc 22080
tgcttcctgg gcaccttcga caagcgcttc ccgggattca tggccccgca caagctggcc 22140
tgcgccatcg tcaacacggc cggccgcgag accgggggcg agcactggct ggccttcgcc 22200
tggaacccgc gctcccacac ctgctacctc ttcgacccct tcgggttctc ggacgagcgc 22260
ctcaagcaga tctaccagtt cgagtacgag ggcctgctgc gccgcagcgc cctggccacc 22320
gaggaccgct gcatcaccct ggaaaagtcc acccagaccg tgcagggtcc gcgctcggcc 22380
gcctgcgggc tcttctgctg catgttcctg cacgccttcg tgcactggcc cgaccgcccc 22440
atggacaaga accccaccat gaacttgctg acgggggtgc ccaacggcat gctccagtcg 22500
ccccaggtgg aacccaccct gcgccgcaac caggaggcgc tctaccgctt cctcaacgcc 22560
cactccgcct actttcgctc ccaccgcgcg cgcatcgaga aggccaccgc cttcgaccgc 22620
atgaatcaag acatgtaaac tgtgtgtatg tgaatgcttt attcatcata ataaacagca 22680
catgtttatg ccaccttctc tgaggctctg actttattta gaaatcgaag gggttctgcc 22740
ggctctcggc gtgccccgcg ggcagggata cgttgcggaa ctggtacttg ggcagccact 22800
tgaactcggg gatcagcagc ttcggcacgg ggaggtcggg gaacgagtcg ctccacagct 22860
tgcgcgtgag ttgcagggcg cccagcaggt cgggcgcgga gatcttgaaa tcgcagttgg 22920
gacccgcgtt ctgcgcgcga gagttgcggt acacggggtt gcagcactgg aacaccatca 22980
gggccgggtg cttcacgctc gccagcaccg tcgcgtcggt gatgccctcc acgtccagat 23040
cctcggcgtt ggccatcccg aagggggtca tcttgcaggt ctgccgcccc atgctgggca 23100
cgcagccggg cttgtggttg caatcgcagt gcagggggat cagcatcatc tgagcctgct 23160
cggagctcat gcccgggtac atggccttca tgaaagcctc cagctggcgg aaggcctgct 23220
gcgccttgcc gccctcggtg aagaagaccc cacaggactt gctagagaac tggttggtgg 23280
cgcagcccgc gtcgtgcacg cagcagcgcg cgtcgttgtt ggccagctgc accacgctgc 23340
gcccccagcg gttctgggtg atcttggccc ggtcggggtt ctccttcagc gcgcgctgcc 23400
cgttctcgct cgccacatcc atctcgatcg tgtgctcctt ctggatcatc acggtcccgt 23460
gcaggcaccg cagcttgccc tcggcctcgg tgcacccgtg cagccacagc gcgcagccgg 23520
tgcactccca gttcttgtgg gcgatctggg agtgcgagtg cacgaagccc tgcaggaagc 23580
ggcccatcat cgtggtcagg gtcttgttgc tggtgaaggt cagcgggatg ccgcggtgct 23640
cctcgttcac atacaggtgg cagatgcggc ggtacacctc gccctgctcg ggcatcagct 23700
ggaaggcgga cttcaggtcg ctctccacgc ggtaccgctc catcagcagc gtcatcactt 23760
ccatgccctt ctcccaggcc gaaacgatcg gcaggctcag ggggttcttc accgtcatct 23820
tagtcgccgc cgccgaagtc agggggtcgt tctcgtccag ggtctcaaac actcgcttgc 23880
cgtccttctc ggtgatgcgc acggggggaa agctgaagcc cacggccgcc agctcctcct 23940
cggcctgcct ttcgtcctcg ctgtcctggc tgatgtcttg caaaggcaca tgcttggtct 24000
tgcggggttt ctttttgggc ggcagaggcg gcggcggaga cgtgctgggc gagcgcgagt 24060
tctcgctcac cacgactatt tcttcttctt ggccgtcgtc cgagaccacg cggcggtagg 24120
catgcctctt ctggggcaga ggcggaggcg acgggctctc gcggttcggc gggcggctgg 24180
cagagcccct tccgcgttcg ggggtgcgct cctggcggcg ctgctctgac tgacttcctc 24240
cgcggccggc cattgtgttc tcctagggag caacaagcat ggagactcag ccatcgtcgc 24300
caacatcgcc atctgccccc gccgccgacg agaaccagca gcagcagaat gaaagcttaa 24360
ccgccccgcc gcccagcccc acctccgacg ccgccgcggc cccagacatg caagagatgg 24420
aggaatccat cgagattgac ctgggctacg tgacgcccgc ggagcacgag gaggagctgg 24480
cagcgcgctt ttcagccccg gaagagaacc accaagagca gccagagcag gaagcagaga 24540
gcgagcagca gcaggctggg ctcgagcatg gcgactacct gagcggggca gaggacgtgc 24600
tcatcaagca tctggcccgc caaagcatca tcgtcaagga cgcgctgctc gaccgcgccg 24660
aggtgcccct cagcgtggcg gagctcagcc gcgcctacga gcgcaacctc ttctcgccgc 24720
gcgtgccccc caagcgccag cccaacggca cctgcgagcc caacccgcgc ctcaacttct 24780
acccggtctt cgcggtgccc gaggccctgg ccacctacca cctctttttc aagaaccaaa 24840
ggatccccgt ctcctgccgc gccaaccgca cccgcgccga cgccctgctc aacctgggtc 24900
ccggcgcccg cctacctgat atcacctcct tggaagaggt tcccaagatc ttcgagggtc 24960
tgggcagcga cgagactcgg gccgcgaacg ctctgcaagg aagcggagag gagcatgagc 25020
accacagcgc cctggtggag ttggaaggcg acaacgcgcg cctggcggtg ctcaagcgca 25080
cggtcgagct gacccacttc gcctacccgg cgctcaacct gccccccaag gtcatgagcg 25140
ccgtcatgga ccaggtgctc atcaagcgcg cctcgcccct ctcagaggag gagatgcagg 25200
accccgagag ctcggacgag ggcaagcccg tggtcagcga cgagcagctg gcgcgctggc 25260
tgggagcgag cagcaccccc cagagcctgg aagagcggcg caagctcatg atggccgtgg 25320
tcctggtgac cgtggagctg gagtgtctgc gccgcttctt cgccgacgcg gagaccctgc 25380
gcaaggtcga ggagaacctg cactacctct tcaggcacgg gttcgtgcgc caggcctgca 25440
agatctccaa cgtggagctg accaacctgg tctcctacat gggcatcctg cacgagaacc 25500
gcctggggca gaacgtgctg cacaccaccc tgcgcgggga ggcccgccgc gactacatcc 25560
gcgactgcgt ctacctgtac ctctgccaca cctggcagac gggcatgggc gtgtggcagc 25620
agtgcctgga ggagcagaac ctgaaagagc tctgcaagct cctgcagaag aacctcaagg 25680
ccctgtggac cgggttcgac gagcgcacca ccgcctcgga cctggccgac ctcatcttcc 25740
ccgagcgcct gcggctgacg ctgcgcaacg ggctgcccga ctttatgagc caaagcatgt 25800
tgcaaaactt tcgctctttc atcctcgaac gctccgggat cctgcccgcc acctgctccg 25860
cactgccctc ggacttcgtg ccgctgacct tccgcgagtg ccccccgccg ctctggagcc 25920
actgctactt gctgcgcctg gccaactacc tggcctacca ctcggacgtg atcgaggacg 25980
tcagcagcga gggtctgctc gagtgccact gccgctgcaa cctctgcacg ccgcaccgct 26040
ccttggcctg caacccccag ctgctgagcg agacccagat catcggcacc ttcgagttgc 26100
aaggccccgg cgagggcaag gggggtctca aactcacccc ggggctgtgg acctcggcct 26160
acttgcgcaa gttcgtgccc gaggactacc atcccttcga gatcaggttc tacgaggacc 26220
aatcccagcc gcccaaggcc gagctgtcgg cctgcgtcat cacccagggg gccatcctgg 26280
cccaattgca agccatccag aaatcccgcc aagaatttct gctgaaaaag ggccacgggg 26340
tctacttgga cccccagacc ggagaggagc tcaaccccag cttcccccag gatgccccga 26400
ggaagcagca agaagctgaa agtggagctg ccgctgccgc cggaggattt ggaggaagac 26460
tgggagagca gtcaggcaga ggagatggaa gactgggaca gcactcaggc agaggaggac 26520
agcctgcaag acagtctgga ggaggaagac gaggtggagg aggaggcaga ggaagaagca 26580
gccgccgcca gaccgtcgtc ctcggcggag gagaaagcaa gcagcacgga taccatctcc 26640
gctccgggtc ggggtcgcgg cggccgggcc cacagtagat gggacgagac cgggcgcttc 26700
ccgaacccca ccacccagac cggtaagaag gagcggcagg gatacaagtc ctggcggggg 26760
cacaaaaacg ccatcgtctc ctgcttgcaa gcctgcgggg gcaacatctc cttcacccgg 26820
cgctacctgc tcttccaccg cggggtgaac ttcccccgca acatcttgca ttactaccgt 26880
cacctccaca gcccctacta ctgtttccaa gaagaggcag aaacccagca gcagcagcag 26940
aaaaccagcg gcagcagcag cagctagaaa atccacagcg gcggcaggtg gactgaggat 27000
cgcggcgaac gagccggcgc agacccggga gctgaggaac cggatctttc ccaccctcta 27060
tgccatcttc cagcagagtc gggggcagga gcaggaactg aaagtcaaga accgttctct 27120
gcgctcgctc acccgcagtt gtctgtatca caagagcgaa gaccaacttc agcgcactct 27180
cgaggacgcc gaggctctct tcaacaagta ctgcgcgctc actcttaaag agtagcccgc 27240
gcccgcccac acacggaaaa aggcgggaat tacgtcacca cctgcgccct tcgcccgacc 27300
atcatcatga gcaaagagat tcccacgcct tacatgtgga gctaccagcc ccagatgggc 27360
ctggccgccg gcgccgccca ggactactcc acccgcatga actggctcag tgccgggccc 27420
gcgatgatct cacgggtgaa tgacatccgc gcccaccgaa accagatact cctagaacag 27480
tcagcgatca ccgccacgcc ccgccatcac cttaatccgc gtaattggcc cgccgccctg 27540
gtgtaccagg aaattcccca gcccacgacc gtactacttc cgcgagacgc ccaggccgaa 27600
gtccagctga ctaactcagg tgtccagctg gccggcggcg ccgccctgtg tcgtcaccgc 27660
cccgctcagg gtataaagcg gctggtgatc cgaggcagag gcacacagct caacgacgag 27720
gtggtgagct cttcgctggg tctgcgacct gacggagtct tccaactcgc cggatcgggg 27780
agatcttcct tcacgcctcg tcaggccgtc ctgactttgg agagttcgtc ctcgcagccc 27840
cgctcgggcg gcatcggcac tctccagttc gtggaggagt tcactccctc ggtctacttc 27900
aaccccttct ccggctcccc cggccactac ccggacgagt tcatcccgaa cttcgacgcc 27960
atcagcgagt cggtggacgg ctacgattga atgtcccatg gtggcgcggc tgacctagct 28020
cggcttcgac acctggacca ctgccgccgc ttccgctgct tcgctcggga tctcgccgag 28080
tttgcctact ttgagctgcc cgaggagcac cctcagggcc cggcccacgg agtgcggatc 28140
gtcgtcgaag ggggcctcga ctcccacctg cttcggattt tcagccagcg tccgatcctg 28200
gtcgagcgcg agcaaggaca gacccttctg accctgtact gcatctgcaa ccaccccggc 28260
ctgcatgaaa gtctttgttg tctgctgtgt actgagtata ataaaagctg agatcagcga 28320
ctactccgga ctcgattgtg gtgttcctgc tatcaaccgg tccctgttct tcaccgggaa 28380
cgagaccgag ctccagctcc agtgtaagcc ccacaagaag tatctcacct ggctgttcca 28440
gggctctccg atcgccgttg tcaaccactg cgacaacgac ggagtcctgc tgagcggccc 28500
tgccaacctt actttttcca cccgcagaag caagctccag ctcttccaac ccttcctccc 28560
cgggacctat cagtgcgtct cgggaccctg ccatcacacc ttccacctga tcccgaatac 28620
cacagcgccg ctccccgcta ctaacaacca aactacccac caacgccacc gtcgcgacct 28680
ttctgaatct aatactacca cccacaccgg aggtgagctc cgaggtcgac caacctctgg 28740
gatttactac ggggttaacc ccttaattaa ggggattcca tatggtacgt acatcgcctc 28800
tcctacgagc tcctgcagca gcgccagaag ttcacctgcc tggtcggagt caaccccatc 28860
gtcatcaccc agcagtcggg cgataccaag gggtgcatcc actgctcctg cgactccccc 28920
gactgcgtcc acactctgat caagaccctc tgcggcctcc gcgacctcct ccccatgaac 28980
taatcacccc cttatccagt gaaataaaga tcatattgat gatgatttta cagaaataaa 29040
gatacaatca tattgatgat ttgagtttaa taaaaaataa agaatcactt acttgaaatc 29100
tgataccagg tctctgtcca tgttttctgc caacaccact tcactcccct cttcccagct 29160
ctggtactgc aggccccggc gggctgcaaa cttcctccac acgctgaagg ggatgtcaaa 29220
ttcctcctgt ccctcaatct tcattttatc ttctatcaga tgtccaaaaa gcgcgtccgg 29280
gtggatgatg acttcgaccc cgtctacccc tacgatgcag acaacgcacc gaccgtgccc 29340
ttcatcaacc cccccttcgt ctcttcagat ggattccaag agaagcccct gggggtgctg 29400
tccctgcgac tggccgaccc cgtcaccacc aagaacgggg aaatcaccct caagctggga 29460
gagggggtgg acctcgactc ctcgggaaaa ctcatctcca acacggccac caaggccgcc 29520
gcccctctca gtttttccaa caacaccatt tcccttaaca tggatcaccc cttttacact 29580
aaagatggaa aattatcctt acaagtttct ccaccattaa atatactgag aacaagcatt 29640
ctaaacacac tagctttagg ttttggatca ggtttaggac tccgtggctc tgccttggca 29700
gtacagttag tctctccact tacatttgat actgatggaa acataaagct taccttagac 29760
agaggtttgc atgttacaac aggagatgca attgaaagca acataagctg ggctaaaggt 29820
ttaaaatttg aagatggagc catagcaacc aacattggaa atgggttaga gtttggaagc 29880
agtagtacag aaacaggtgt tgatgatgct tacccaatcc aagttaaact tggatctggc 29940
cttagctttg acagtacagg agccataatg gctggtaaca aagaagacga taaactcact 30000
ttgtggacaa cacctgatcc atcgccaaac tgtcaaatac tcgcagaaaa tgatgcaaaa 30060
ctaacacttt gcttgactaa atgtggtagt caaatactgg ccactgtgtc agtcttagtt 30120
gtaggaagtg gaaacctaaa ccccattact ggcaccgtaa gcagtgctca ggtgtttcta 30180
cgttttgatg caaacggtgt tcttttaaca gaacattcta cactaaaaaa atactggggg 30240
tataggcagg gagatagcat agatggcact ccatatacca atgctgtagg attcatgccc 30300
aatttaaaag cttatccaaa gtcacaaagt tctactacta aaaataatat agtagggcaa 30360
gtatacatga atggagatgt ttcaaaacct atgcttctca ctataaccct caatggtact 30420
gatgacagca acagtacata ttcaatgtca ttttcataca cctggactaa tggaagctat 30480
gttggagcaa catttggggc taactcttat accttctcat acatcgccca agaatgaaca 30540
ctgtatccca ccctgcatgc caacccttcc caccccactc tgtggaaaaa actctgaaac 30600
acaaaataaa ataaagttca agtgttttat tgattcaaca gttttacagg attcgagcag 30660
ttatttttcc tccaccctcc caggacatgg aatacaccac cctctccccc cgcacagcct 30720
tgaacatctg aacgccattg gtgatggaca tgcttttggt ctccacgttc cacacagttt 30780
cagagcgagc cagtctcggg tcggtcaggg agatgaaacc ctccgggcac aattgggaga 30840
agtactcgcc tattatctgg aagaagcaga agagcggcgg tgggaatcat agtccgcgaa 30900
cgggatcggc cggtggtgtc gcatcaggcc ccgcagcagt cgctgccgcc gccgctccgt 30960
caagctgctg ctcagggggt ccgggtccag ggactccctc agcatgatgc ccacggccct 31020
cagcatcagt cgtctggtgc ggcgggcgca gcagcgcatg cggatctcgc tcaggtcgct 31080
gcagtacgtg caacacagaa ccaccaggtt gttcaacagt ccatagttca acacgctcca 31140
gccgaaactc atcgcgggaa ggatgctacc cacgtggccg tcgtaccaga tcctcaggta 31200
aatcaagtgg tgccccctcc agaacacgct gcccacgtac atgatctcct tgggcatgtg 31260
gcggttcacc acctcccggt accacatcac cctctggttg aacatgcagc cccggatgat 31320
cctgcggaac cacagggcca gcaccgcccc gcccgccatg cagcgaagag accccgggtc 31380
ccggcaatgg caatggagga cccaccgctc gtacccgtgg atcatctggg agctgaacaa 31440
gtctatgttg gcacagcaca ggcatatgct catgcatctc ttcagcactc tcaactcctc 31500
gggggtcaaa accatatccc agggcacggg gaactcttgc aggacagcga accccgcaga 31560
acagggcaat cctcgcacag aacttacatt gtgcatggac agggtatcgc aatcaggcag 31620
caccgggtga tcctccacca gagaagcgcg ggtctcggtc tcctcacagc gtggtaaggg 31680
ggccggccga tacgggtgat ggcgggacgc ggctgatcgt gttcgcgacc gtgtcatgat 31740
gcagttgctt tcggacatat ttcctgaagt cttggcgcgc caaagtctag acagcgtcca 31800
tagcttaccg agcagcagca gcagcacaca acaggcgcaa gagtcagaga aaggctgagc 31860
tctaacctgt ccacccgctc tctgctcaat atatagccca gatctacact gacgtaaagg 31920
ccaaagtcta aaaatacccg ccaaatagtc acacacgccc agcacacgcc cagaaaccgg 31980
tgacacactc aaaaaaatac gcgcacttcc tcaaacgccc aaactgccgt catttccggg 32040
ttcccacgct acgtcatcaa aacacgactt tcaaattccg tcgaccgtta aaaacgtcac 32100
ccgccccgcc cctaacggtc gcccgtctct cagccaatca gcgccccgca tccccaaatt 32160
caaacacctc atttgcatat taacgcgcac caaaagtttg aggtatatta ttgatgatga 32220
ttt 32223

Claims (9)

1. A norovirus vaccine is characterized in that the vaccine is a norovirus recombinant adenovirus vaccine with immunogenicity, which is obtained by inserting the nucleotide sequence of a norovirus target protein into a recombinant chimpanzee adenovirus vector plasmid to construct a recombinant plasmid, and then packaging and processing the recombinant plasmid;
the norovirus vaccine encodes the VP1 protein of norovirus;
the norovirus is GII.4 type, the amino acid sequence of the norovirus GII.4 type VP1 protein is SEQ ID NO. 1, and the DNA sequence of the norovirus GII.4 type VP1 protein is SEQ ID NO. 2.
2. Norovirus vaccine according to claim 1, wherein the recombinant chimpanzee adenovirus vector is a replication-defective type 63 or replication-defective type 3 adenovirus.
3. The norovirus vaccine of claim 2, wherein the norovirus vaccine is prepared by a method comprising the steps of:
1) inserting the nucleotide sequence of the norovirus target protein into a recombinant chimpanzee adenovirus vector plasmid to construct a recombinant plasmid;
2) after enzyme digestion linearization, the recombinant plasmid is transfected into adenovirus packaging cells, and then cultured until 80% of the cells have obvious cytopathic effect;
3) collecting cells, breaking the cells by adopting a repeated freeze thawing mode, and centrifugally collecting supernate;
4) infecting adenovirus packaging cells with the supernatant, and culturing until the cells change from adherent to suspension state;
5) performing repeated amplification culture according to the steps 3) and 4), collecting cells, crushing, and centrifuging supernatant;
6) and (3) purifying the recombinant adenovirus by taking the supernatant to obtain purified virus liquid, wherein the virus liquid is norovirus recombinant adenovirus vaccine stock solution.
4. The norovirus vaccine of claim 3, wherein the recombinant chimpanzee adenovirus vector plasmid is constructed by modifying the wild-type chimpanzee adenovirus 63 or type 3 genomic sequence to remove and/or replace the E1, E3, and E4 regions, and inserting the modified sequence into a transfer vector plasmid.
5. The norovirus vaccine of claim 4, wherein the recombinant chimpanzee adenovirus vector plasmid is a recombinant vector plasmid constructed by modifying a wild-type chimpanzee adenovirus type 63 genome sequence to remove and/or replace the E1, E3, and E4 regions, and inserting the modified sequence into a transfer vector plasmid; the DNA sequence of the recombinant chimpanzee adenovirus vector plasmid is SEQ ID NO. 3, and the modified replication-defective chimpanzee adenovirus type 63 genome sequence contained in the recombinant chimpanzee adenovirus vector plasmid is SEQ ID NO. 4.
6. The norovirus vaccine of claim 5, wherein the recombinant plasmid is an open reading frame with the norovirus GII.4 VP1 gene inserted between E1 modification site MluI and EcoRI in the recombinant chimpanzee adenovirus type 63 genome sequence contained in the vector plasmid, the open reading frame is an expression frame sequence of norovirus GII.4 VP1 initiated by a CMV promoter, and the DNA sequence of the open reading frame is shown in SEQ ID NO. 5.
7. The norovirus vaccine of claim 6, wherein the recombinant plasmid is constructed by a method comprising: after the open reading frame sequence of the norovirus GII.4 type VP1 gene is completely designed in sequence analysis software, a recombinant adenovirus vector plasmid pChAD63-GII.4 capable of expressing the norovirus GII.4 type VP1 protein is obtained in a gene synthesis mode, and the nucleotide sequence of the recombinant adenovirus vector plasmid is shown as SEQ ID NO. 6.
8. The norovirus vaccine of claim 7, wherein the norovirus recombinant adenovirus obtained after the recombinant plasmid is linearized by digestion and transfected into an adenovirus packaging cell is a recombinant chimpanzee adenovirus type 63 virus ChAd63-gii.4 comprising the antigen sequence of norovirus type gii.4 VP1, the complete genome sequence of which is SEQ ID No. 7.
9. Use of a norovirus vaccine according to any one of claims 1-8 for the preparation of a medicament or kit for the prevention or treatment of a norovirus-related disease.
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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN114272368A (en) * 2021-12-16 2022-04-05 成都博宠生物科技有限公司 Swine fever and porcine pseudorabies bivalent vaccine as well as preparation method and application thereof
CN115161343A (en) * 2021-04-01 2022-10-11 苏州相奕生物技术有限公司 Recombinant adenovirus expression vector and multivalent norovirus vaccine prepared by same
CN115161343B (en) * 2021-04-01 2024-06-04 苏州相奕生物技术有限公司 Recombinant adenovirus expression vector and multivalent norovirus vaccine prepared from recombinant adenovirus expression vector

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104968782A (en) * 2012-12-26 2015-10-07 生物科莫公司 Vaccine prepared utilizing human parainfluenza virus type 2 vector
CN109776657A (en) * 2017-11-14 2019-05-21 北京康乐卫士生物技术股份有限公司 Recombinate norovirus VLP particle and preparation method and its usage
CN109804075A (en) * 2016-08-01 2019-05-24 威斯塔解剖学和生物学研究所 The composition and method of replication-defective adenoviral vector for vaccine application
CN110551212A (en) * 2019-09-29 2019-12-10 中国医学科学院医学生物学研究所 Preparation method and application of anti-GII.4 norovirus capsid protein VP1 and VLP (virus-like particle) monoclonal antibody

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104968782A (en) * 2012-12-26 2015-10-07 生物科莫公司 Vaccine prepared utilizing human parainfluenza virus type 2 vector
CN109804075A (en) * 2016-08-01 2019-05-24 威斯塔解剖学和生物学研究所 The composition and method of replication-defective adenoviral vector for vaccine application
CN109776657A (en) * 2017-11-14 2019-05-21 北京康乐卫士生物技术股份有限公司 Recombinate norovirus VLP particle and preparation method and its usage
CN110551212A (en) * 2019-09-29 2019-12-10 中国医学科学院医学生物学研究所 Preparation method and application of anti-GII.4 norovirus capsid protein VP1 and VLP (virus-like particle) monoclonal antibody

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
LI GUO等: "Intranasal administration of a recombinant adenovirus expressing the norovirus capsid protein stimulates specific humoral，mucosal，and cellular immune responses in mice", 《VACCINE》 *
LISA C. LINDESMITH: "Sera Antibody Repertoire Analyses Reveal Mechanisms of Broad and Pandemic Strain Neutralizing Responses after Human Norovirus Vaccination", 《IMMUNITY》 *

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN115161343A (en) * 2021-04-01 2022-10-11 苏州相奕生物技术有限公司 Recombinant adenovirus expression vector and multivalent norovirus vaccine prepared by same
CN115161343B (en) * 2021-04-01 2024-06-04 苏州相奕生物技术有限公司 Recombinant adenovirus expression vector and multivalent norovirus vaccine prepared from recombinant adenovirus expression vector
CN114272368A (en) * 2021-12-16 2022-04-05 成都博宠生物科技有限公司 Swine fever and porcine pseudorabies bivalent vaccine as well as preparation method and application thereof

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