Patent application title: METHOD OF TREATING PREGNANT COWS AND/OR HEIFERS
Inventors:
Carol L. Rinehart (Parkville, MO, US)
Craig Jones (Kansas City, MO, US)
Judy Myers-Kuhnhoff (Weatherby Lake, MO, US)
Wayne Cole (St. Joseph, MO, US)
William Charles Ohnesorge (St. Joseph, MO, US)
Assignees:
BOEHRINGER INGELHEIM VETMEDICA, INC.
IPC8 Class: AA61K39295FI
USPC Class:
4242011
Class name: Drug, bio-affecting and body treating compositions antigen, epitope, or other immunospecific immunoeffector (e.g., immunospecific vaccine, immunospecific stimulator of cell-mediated immunity, immunospecific tolerogen, immunospecific immunosuppressor, etc.) combination of viral and bacterial antigens (e.g., multivalent viral and bacterial vaccine, etc.)
Publication date: 2014-12-11
Patent application number: 20140363466
Abstract:
The present invention relates to combination vaccines for the prophylaxis
and treatment of microbiological infections in cattle which comprise an
attenuated bovine viral diarrhea virus (BVDV) for the the prophylaxis and
treatment of BVDV caused infections. The invention also relates to a
method of vaccinating a pregnant cow.Claims:
1. A method of preventing abortion in a pregnant cow, comprising
administering a first vaccine to the cow prior to pregnancy wherein said
first vaccine comprises a therapeutically effective amount of Infectious
Bovine Rhinotracheitis (IBR), Bovine Viral Diarrhea Virus (BVDV) Type I
and BVDV Type 2 and administering a second vaccine to the cow after the
cow is pregnant, wherein said second vaccine comprises modified live IBR
virus, modified live BVDV Type 1 derived from a Singer strain, modified
live BVDV Type 2 derived from Strain 296, and Haemophilus somnus.
2. The method of claim 1, wherein the modified BVDV Singer strain is the one that is included in the BREED-BACK® FP5 vaccine.
3. The method of claim 1, wherein the modified live BVDV Type 2 Strain 296 is the one that is included in the BREED-BACK® FP5 vaccine.
4. The method of claim 1, wherein the modified live IBR is IBR Colorado 1 Strain.
5. The method of claim 4, wherein the modified live IBR Colorado 1 Strain is the one that is included in the BREED-BACK® FP5 vaccine.
6. The method of claim 1, wherein the second vaccine further comprises an immunologically active component effective for treatment or prophylaxis of an infection caused by a Leptospira bacterium.
7. The method of claim 6, wherein the Leptospira bacterium is selected from the group consisting of: Leptospira canicola, Leptospira grippotyphosa, Leptospira hardjo, Leptospira icterohaemorrhagiae, and Leptospira pomona.
8. The method of claim 6, wherein the Leptospira bacterium comprises Leptospira canicola, Leptospira grippotyphosa, Leptospira hardjo, Leptospira icterohaemorrhagiae, and Leptospira pomona.
9. The method of claim 1, wherein the second vaccine is selected from the group consisting of BREED-BACK® FP5-HS, EXPRESS® 5-HS®, EXPRESS® FP5-HS , BREED-BACK® FP10, EXPRESS® 10, BREEDBACK® FP10-HS, EXPRESS FP10-HS®, and combinations thereof.
10. The method of claim 1, further comprising the step of administering the second vaccine to the pregnant cow during the first, second or third trimester of pregnancy.
11. The method of claim 1, wherein the second vaccine prevents the incidence of one or more clinical signs of an infection caused by a microbe selected from the group consisting of Infectious Bovine Rhinotracheitis (IBR), Bovine Viral Diarrhea Virus (BVDV) Type 1, BVDV Type 2, and any combination thereof in a pregnant cow.
12. The method of claim 1, wherein the second vaccine prevents the incidence of one or more clinical signs of an infection caused by a microbe selected from the group consisting of Infectious Bovine Rhinotracheitis (IBR), Bovine Viral Diarrhea Virus (BVDV) Type 1, BVDV Type 2, and any combination thereof in a fetus of a pregnant cow.
13. The method of claim 1, wherein the pregnant cow is a pregnant heifer.
14. The method of claim 1, wherein the modified BVDV Singer strain is the one that is included in the BREED-BACK® FP5 vaccine.
15. The method of claim 1, wherein the modified live BVDV Type 2 Strain 296 is the one that is included in the BREED-BACK® FP5 vaccine.
16. The method of claim 1, wherein the modified live IBR is IBR Colorado 1 Strain.
17. The method of claim 16, wherein the modified live IBR Colorado 1 Strain is the one that is included in the BREED-BACK® FP5 vaccine.
18. The method of claim 1, wherein the first vaccine further comprises an immunologically active component effective for treatment or prophylaxis of an infection caused by a Leptospira bacterium.
19. The method of claim 18, wherein the Leptospira bacterium is selected from the group consisting of: Leptospira canicola, Leptospira grippotyphosa, Leptospira hardjo, Leptospira icterohaemorrhagiae, and Leptospira pomona.
Description:
SEQUENCE LISTING
[0001] This application contains a sequence listing in computer readable format, the teachings and content of which are hereby incorporated by reference.
FIELD OF THE INVENTION
[0002] The present invention relates to the field of animal health and in particular to vaccines which comprise an attenuated bovine viral diarrhea virus (BVDV). More particularly, the present invention relates to the use of modified live BVDV Type 1 and BVDV Type 2 vaccines. Still more particularly, the present invention relates to the use of such vaccines in pregnant cows/heifers. Even more particularly, the vaccines will include other antigens from bovine pathogens in addition to the BVDV Type 1 and BVDV Type 2 modified live vaccines.
BACKGROUND OF THE INVENTION
[0003] Cows are susceptible to contracting a large diversity of microbial infections. A number of effective vaccines have been developed to treat or prevent infection. Vaccines that are based on modified live viruses, however, pose a risk to the health of pregnant cows and their calves. Accordingly, there is a need for safe methods of vaccinating pregnant cows.
[0004] Bovine viral diarrhea virus (BVDV) Type 1 (BVDV-1) and Type 2 (BVDV-2) cause bovine viral diarrhea (BVD) and mucosal disease (MD) in cattle, as well as cause abortions and fetal infections that may result in persistently infected calves (Baker, 1987; Moennig and Plagemann, 1992;). The division of BVDV into 2 species is based on significant differences at the level of genomic sequences (summarized in Heinz et al., 2000) which are also obvious from limited cross neutralizing antibody reactions. The viral proteins of BVDV, and any other virus of the pestivirus family, are arranged in the polyprotein in the order NH2-N.sup.pro-C-E.sup.rns-E1-E2-p7-NS2-NS3-NS4A-NS4B-NS5A-NS5B-COOH (Lindenbach and Rice, 2001).
[0005] Present BVDV vaccines for the prevention and treatment of BVDV infections still have drawbacks. Vaccines against the classical BVDV-1 provide only partial protection from BVDV-2 infection, and vaccinated dams may produce calves that are persistently infected with virulent BVDV-2. This problem is probably due to the great antigenic diversity between type 1 and type 2 strains which is most pronounced in the glycoprotein E2, the major antigen for virus neutralization. Most monoclonal antibodies against type 1 strains fail to bind to type 2 viruses.
[0006] Currently, licensed BVDV MLV vaccines are produced using attenuated viruses obtained via repeated passage in bovine or porcine cells, or using chemically modified viruses which exhibit a temperature-sensitive phenotype. A single dose of MLV vaccine is sufficient for immunization, and duration of the immunity can last for years in vaccinated cattle. However, these vaccines, although attenuated, are often associated with safety problems. Prior art has taught that the vaccine viruses may cross the placenta of pregnant animals, e.g. cows or heifers and lead to clinical manifestations in the fetus and/or the induction of persistently infected calves. Therefore, it is recommended that they not be applied or administered to breeding herds that contain pregnant cows. Pregnant cows have to be kept separate from vaccinated cattle to protect fetuses and must not be vaccinated themselves.
[0007] Bovine Herpesvirus (BHV-1) or Infectious bovine rhinotracheitis (IBR) virus is associated with several diseases and symptoms in cattle: Infectious bovine rhinotracheitis (IBR), infectious pustular vulvovaginitis (IPV), balanoposthitis, conjunctivitis, abortion, encephalomyelitis, and mastitis. Only a single serotype of BHV-1 is recognized; however, three subtypes of BHV-1 have been described on the basis of endonuclease cleavage patterns of viral DNA. These types are referred to as BHV-1.1 (respiratory subtype), BHV-1.2 (genital subtype), and BHV-1.3 (encephalitic subtype). Recently, BHV-1.3 has been reclassified as a distinct herpesvirus designated BHV-5. BHV-1 infections are widespread in the cattle population. In feedlot cattle, the respiratory form is most common. The viral infection alone is not life-threatening but predisposes cattle to secondary bacterial pneumonia, which may result in death. In breeding cattle, abortion or genital infections are more common. Genital infections can occur in bulls (infectious pustular balanoposthitis) and cows (IPV) within 1-3 days of mating or close contact with an infected animal. Transmission can occur in the absence of visible lesions and through artificial insemination with semen from subclinically infected bulls. Cattle with latent BHV-1 infections generally show no clinical signs when the virus is reactivated, but they do serve as a source of infection for other susceptible animals and thus perpetuate the disease. The incubation period for the respiratory and genital forms is 2-6 days. In the respiratory form, clinical signs range from mild to severe, depending on the presence of secondary bacterial pneumonia. Clinical signs include pyrexia, anorexia, coughing, excessive salivation, nasal discharge that progresses from serous to mucopurulent, conjunctivitis with lacrimal discharge, inflamed nares (hence the common name "red nose"), and dyspnea if the larynx becomes occluded with purulent material. Pustules may develop on the nasal mucosa and later form diphtheritic plaques. Conjunctivitis with corneal opacity may develop as the only manifestation of BHV-1 infection. In the absence of bacterial pneumonia, recovery generally occurs 4-5 days after the onset of clinical signs. Abortions may occur concurrently with respiratory disease but can also occur up to 100 days after infection. Abortions can occur regardless of the severity of disease in the dam. Abortions generally occur during the second half of pregnancy, but early embryonic death may also occur. The first signs of genital infections in cows are frequent urination, elevation of the tailhead, and a mild vaginal discharge. The vulva is swollen, and small papules, then erosions and ulcers, are present on the mucosal surface. If secondary bacterial infections do not occur, animals recover in 10-14 days. If bacterial infection occurs, there may be inflammation of the uterus and transient infertility, with purulent vaginal discharge for several weeks. In bulls, similar lesions occur on the penis and prepuce. BHV-1 infection can be severe in young calves and cause a generalized disease. Pyrexia, ocular and nasal discharges, respiratory distress, diarrhea, incoordination, and eventually convulsions and death may occur in a short period after generalized viral infection. IBR is rarely fatal in cattle unless complicated by bacterial pneumonia. In uncomplicated IBR infections, most lesions are restricted to the upper respiratory tract and trachea. Petechial to ecchymotic hemorrhages may be found in the mucous membranes of the nasal cavity and the paranasal sinuses. Focal areas of necrosis develop in the nose, pharynx, larynx, and trachea. The lesions may coalesce to form plaques. The sinuses are often filled with a serous or serofibrinous exudate. As the disease progresses, the pharynx becomes covered with a serofibrinous exudate, and blood-tinged fluid may be found in the trachea. The pharyngeal and pulmonary lymph nodes may be acutely swollen and hemorrhagic. The tracheitis may extend into the bronchi and bronchioles; when this occurs, epithelium is sloughed in the airways. The viral lesions are often masked by secondary bacterial infections. In young animals with generalized BHV-1 infection, erosions and ulcers overlaid with debris may be found in the nose, esophagus, and forestomachs. In addition, white foci may be found in the liver, kidney, spleen, and lymph nodes. Aborted fetuses may have pale, focal, necrotic lesions in all tissues, but which are especially visible in the liver.
[0008] Parainfluenza-3 virus (PI-3) is an RNA virus classified in the paramyxovirus family. Infections caused by PI-3 are common in cattle. Although PI-3 is capable of causing disease, it is usually associated with mild to subclinical infections. The most important role of PI-3 is to serve as an initiator that can lead to the development of secondary bacterial pneumonia. Clinical signs include pyrexia, cough, serous nasal and lacrimal discharge, increased respiratory rate, and increased breath sounds. The severity of signs worsen with the onset of bacterial pneumonia. Fatalities from uncomplicated PI-3 pneumonia are rare. Lesions include cranioventral lung consolidation, bronchiolitis, and alveolitis with marked congestion and hemorrhage. Inclusion bodies may be identified. Most fatal cases will also have a concurrent bacterial bronchopneumonia.
[0009] Bovine Respiratory Syncytial Virus (BRSV) is an RNA virus classified as a pneumovirus in the paramyxovirus family. In addition to cattle, sheep and goats can also be infected by respiratory syncytial viruses. This virus was named for its characteristic cytopathic effect--the formation of syncytial cells. Antigenic subtypes are known to exist for BRSV, and preliminary evidence suggests that there may be antigenic subtypes of BRSV. BRSV is distributed worldwide, and the virus is indigenous in the cattle population. BRSV infections associated with respiratory disease occur predominantly in young beef and dairy cattle. Passively derived immunity does not appear to prevent BRSV infections but will reduce the severity of disease. Initial exposures to the virus are associated with severe respiratory disease; subsequent exposures result in mild to subclinical disease. BRSV appears to be an important virus in the bovine respiratory disease complex because of its frequency of occurrence, predilection for the lower respiratory tract, and its ability to predispose the respiratory tract to secondary bacterial infection. In outbreaks, morbidity tends to be high, and case fatality can be 0-20%. Signs include increased rectal temperature (40-42° C.), depression, decreased feed intake, increased respiratory rate, cough, and nasal and lacrimal discharge. Generally, respiratory signs predominate. Dyspnea may become pronounced in the later stages of the disease. Subcutaneous emphysema is sometimes reported. Secondary bacterial pneumonia is a frequent occurrence. A biphasic disease pattern has been described but is not consistent. Gross lesions include a diffuse interstitial pneumonia with subpleural and interstitial emphysema along with interstitial edema. These lesions are similar to and must be differentiated from other causes of interstitial pneumonia. See also atypical interstitial pneumonia. Histologic examination reveals syncytial cells in bronchiolar epithelium and lung parenchyma, intracytoplasmic inclusion bodies, proliferation and/or degeneration of bronchiolar epithelium, alveolar epithelialization, edema, and hyaline membrane formation.
[0010] Leptospirosis is a contagious disease of animals, including man, caused by various immunologically distinct leptospiral serovars, most of which are regarded as subgroups of Leptospira interrogans. Infections may be asymptomatic or cause various signs, including fever, icterus, hemoglobinuria, renal failure, infertility, abortion, and death. After acute infection, leptospires frequently localize in the kidneys or reproductive organs and are shed in the urine, sometimes in large numbers for months or years. Because the organisms survive in surface waters for extended periods, the disease is often waterborne. In the USA, the disease is primarily due to the serovars Leptospira hardjo, Leptospira pomona, and Leptospira grippotyphosa. However, Leptospira canicola and icterohaemorrhagiae serovars also have been isolated. Calves may have fever, anorexia, and dyspnea, and in Leptospira pomona infections, icterus, hemoglobinuria, and anemia. Body temperature may rise suddenly to 40.5-41° C. Hemoglobinuria rarely lasts longer than 48-72 hrs. Icterus clears rapidly and is followed by anemia. The RBC's begin to increase in number by 4-5 days and return to normal 7-10 days later. However, Leptospira hardjo infections usually do not cause hemolytic anemia, which makes diagnosis more difficult. Morbidity and mortality are higher in calves than in adult cattle. In older cattle, signs vary greatly and diagnosis is more difficult. Enzootic Leptospira hardjo infections, which usually result in abnormal milk, are more obvious in dairy than in beef cattle. Signs usually are restricted to lowered milk and calf production; a hemolytic crisis does not occur. The milk is thick, yellow, and blood-tinged; it may contain clots, although there is little evidence of mammary inflammation. Milk production returns to normal in 10-14 days, even in the absence of treatment. Abortion and stillbirths, which are common in Leptospira pomona infections and sporadic in Leptospira hardjo infections, generally occur 3-10 weeks after initial infection. The abortions are more common during the third trimester. An abortion storm in a breeding herd is often the first indication that leptospirosis exists, because the mild initial signs often pass unnoticed. In endemically infected herds, abortions occur mostly in younger animals and are sporadic, rather than being manifested as abortion storms. Calves reared by previously infected cows are protected by colostral antibodies for up to 6 mos. The calves generally have an antibody titer similar to that of their dams. In the acute form, anemia, icterus, hemoglobinuria, and submucosal hemorrhages are prominent. The kidneys are swollen, with multifocal petechial and ecchymotic hemorrhages that become pale with time. The liver may be swollen, with minute areas of focal necrosis. Petechiae in other organs are seen in fulminating cases; however, in the more prevalent Leptospira hardjo infections, the lesions are primarily restricted to the kidneys.
[0011] Haemophilus somnus is being increasingly recognized as an important pathogen in BRD; these bacteria are normal inhabitants of the nasopharynx of cattle. H. somnus infection of the lungs results in purulent bronchopneumonia that may be followed by septicemia and infection of multiple organs. Occasionally, H. somnus is associated with extensive pleuritis. H. somnus can cause an acute, usually fatal, septicemic disease that can involve the nervous, musculoskeletal, circulatory, and respiratory systems, either singly or together. The reproductive system is often affected but usually without the other systems being clinically involved. The disease may be characterized by fever, severe depression, ataxia, weakness, blindness, coma, and death within several hours to several days. It occurs sporadically in individual beef and dairy cattle and is found nearly worldwide. H. somnus is a gram-negative, nonmotile, nonsporeforming, pleomorphic coccobacillus that requires an enriched medium and a microaerophilic atmosphere for culture.
DESCRIPTION OF THE INVENTION
[0012] One aspect of the present invention provides a method for safely vaccinating a pregnant cow, wherein the method generally includes or comprises the step of administering a vaccine to the pregnant cow or pregnant heifer. The vaccine preferably includes an immunological active component effective for treating or prophylaxis of an infection caused by a microbe selected from the group consisting of: Infectious Bovine Rhinotracheitis (IBR), Bovine Viral Diarrhea Virus (BVDV) Type 1, BVDV Type 2, Parainfluenza-3 Virus (PI-3), Bovine Respiratory Syncytial Virus (BRSV), and combinations thereof. The pregnant cow or heifer can be in the first, second, or third trimester of pregnancy when the vaccine is administered. In preferred forms of this vaccine, the immunological active components effective for treating or prophylaxis of infection caused by BVDV Type 1 and/or BVDV Type 2 is a modified live BVDV. In other preferred forms, the immunological active component effective for treating or prophylaxis of infection caused by IBR is a modified live IBR. Preferred vaccine compositions will include both BVDV Type 1 and BVDV Type 2 immunological active components, even more preferably both the BVDV Type 1 and BVDV Type 2 immunological active components will be modified live BVDV, still more preferably, preferred vaccine compositions will further include IBR immunological active components, preferably modified live IBR. In even further preferred vaccine compositions, PI-3 immunological active components will be included. In still further preferred vaccine compositions, BRSV immunological active components will be included. Representative vaccines that can be used in a method according to the invention including modified live BVDV Type I, modified live BVDV Type II, modified live IBR, PI-3, and BRSV that are sold under the names BREED-BACK® FP5, EXPRESS® FP5, and EXPRESS® 5 (Boehringer Ingelheim Vetmedica, Inc., St. Joseph, Mo.).
[0013] According to a further aspect the present invention relates to the vaccination of pregnant cows/heifers comprising the step of administering to a pregnant cow/heifer a modified live BVDV Type 1, preferably a cytopathic modified lived BVDV Type 1, which is derived from the Singer strain, a modified live BVDV Type 2, preferably a cytopathic modified live BVDV Type 2, which is derived from the 296 strain, and/or a modified live IBR which is derived from the IBR Colorado 1 Strain. Preferably the modified live BVDV Type 1 Singer strain is the one that is included in the BREED-BACK® FP5 vaccine. Preferably the modified live BVDV Type 2 296 strain is the one that is included in the BREED-BACK® FP5 vaccine. Preferably the modified live IBR strain is the one that is included in the BREED-BACK® FP5 vaccine. Preferably the vaccine is administered to prevent, or reduce the incidence of or severity of an infection in the pregnant cow and preferably its fetus with or at least the clinical signs caused by BVDV Type 1, BVDV Type 2, and/or IBR (each depending from the antigen/antigen combination that is/are used--modified live BVDV Type I, modified live BVDV Type 2, modified live IBR or any combination thereof).
[0014] In other aspect the present invention also relates to a method for vaccinating pregnant cows/heifers comprising the step of administering to said pregnant cow/heifer a vaccine which comprises a vaccine composition and/or immunological active components of Haemophilus somnus, preferably in a bacterin form, in addition to the modified live BVDV Type 1, modified live BVDV Type 2, and/or modified live IBR, described above. Preferably said vaccine further comprises PI-3 and BRSV immunological active components. Representative vaccines including modified live BVDV Type 1, modified live BVDV Type 2, modified live IBR, PI-3, BRSV, and Haemophilus somnus bacterin that can be used for the vaccination of pregnant cows as described herein are sold under the names BREED-BACK® FP5-HS and EXPRESS® 5-HS (Boehringer Ingelheim Vetmedica, Inc., St. Joseph, Mo.).
[0015] According to a further aspect, the vaccine composition that can be used for the vaccination of pregnant cows/heifers as described herein further comprises a vaccine composition or immunological active component effective for treating or preventing an infection caused by a Leptospira bacterium. In preferred forms of such vaccine composition, the immunological active component will be a Leptospira bacterin. Still more preferably, the bacterin will be derived from a Leptospira bacterium selected from the group consisting of: Leptospira canicola, Leptospira grippotyphosa, Leptospira hardjo, Leptospira icterohaemorrhagiae, Leptospira Pomona, and combinations thereof. Some preferred vaccine compositions will include Leptospira bacterin derived from Leptospira canicola, Leptospira grippotyphosa, Leptospira hardjo, Leptospira icterohaemorrhagiae, and Leptospira pomona. Representative vaccines including modified live BVDV Type 1, modified live BVDV Type 2, modified live IBR, PI-3, BRSV, Haemophilus somnus bacterin, and Leptospira bacterin derived from Leptospira canicola, Leptospira grippotyphosa, Leptospira hardjo, Leptospira icterohaemorrhagiae, and Leptospira pomona that can be used for the vaccination of pregnant cows/heifers as described herein are sold under the names BREED-BACK® FP10-HS and EXPRESS 10-HS® (Boehringer Ingelheim Vetmedica, Inc., St. Joseph, Mo). Representative vaccines including modified live BVDV Type 1, modified live BVDV Type 2, modified live IBR, PI-3, BRSV, and Leptospira bacterin derived from Leptospira canicola, Leptospira grippotyphosa, Leptospira hardjo, Leptospira icterohaemorrhagiae, and Leptospira pomona that can be used for the vaccination of pregnant cows/heifers as described herein are sold under the names BREED-BACK® FP10 and EXPRESS®10 (Boehringer Ingelheim Vetmedica, Inc., St. Joseph, Mo.).
[0016] According to a further aspect, the vaccine composition that can be used for the vaccination of pregnant cows/heifers as described herein further comprises at least one further immunolical active component which can prevent the pregnant cow/heifer from microbiological infections of other cattle relevant pathogens or at least from the clinical signs caused by said other cattle relevant pathogens. A list of those pathogens and vaccine compositions which are also suitable to be used according to the present invention are disclosed in the international patent application published as WO 2007-117303, the entire teachings and content of which is incorporated herein by reference.
[0017] For all of the vaccine compositions described above and that can be used for the vaccination of pregnant cows/heifers as described herein, the modified live viruses used therein are preferably attenuated. A particularly preferred modified live BVDV Type 1 is derived from a Singer strain of BVDV. Even more preferably, the Singer strain of BVDV has been passaged at least two times in bovine turbinate cells. Most preferably the modified BVDV Singer strain is the one that is included in the BREED-BACK® FP5 vaccine. A particularly preferred modified live BVD Type 2 is derived from BVDV Strain 296. Even more preferably, the BVDV Strain 296 has been passaged in bovine testicular cells or MDBK cells, or embryonic swine kidney cells (ESK cells). In particularly preferred forms, the BVDV Strain 296 has been passaged in bovine testicular cells at least six times and in MDBK and ESK cells at least 23 times. Most preferably the modified BVDV 296 strain is the one that is included in the BREED-BACK® FP5 vaccine.
[0018] A particularly preferred modified live IBR strain is derived from the IBR Colorado 1 strain. Even more preferably, the IBR Colorado 1 Strain 1 has been passaged 4 times in bovine embryo kidney cells, 22 times in ovine cells and once in MDBK cells. Most preferably the modified IBR strain is the one that is included in the BREED-BACK® FP5 vaccine. In other preferred forms of practicing the invention, in addition to the administration of any vaccine composition described above to a pregnant cow or heifer, the vaccine composition is also administered to the cow prior to the pregnancy. Preferably, such administration is performed within 12 months of the pregnancy, still more preferably within 10 months, even more preferably within 8 months, still more preferably within 7 months, even more preferably within 6 months, still more preferably within 5 months, even more preferably within 4 months, still more preferably within 3 months, even more preferably within 2 months, and most preferably between about 1 and two months prior to pregnancy.
[0019] In some preferred forms of any of the vaccine compositions described above, the composition will include at least one additional component selected from the group consisting of pharmaceutical acceptable carriers, adjuvants, diluents, preservatives, antibiotics, and combinations thereof.
[0020] "Adjuvants" as used herein, can include aluminum hydroxide and aluminum phosphate, saponins e.g., Quil A, QS-21 (Cambridge Biotech Inc., Cambridge Mass.), GPI-0100 (Galenica Pharmaceuticals, Inc., Birmingham, Ala.), water-in-oil emulsion, oil-in-water emulsion, water-in-oil-in-water emulsion. The emulsion can be based in particular on light liquid paraffin oil (European Pharmacopea type); isoprenoid oil such as squalane or squalene oil resulting from theoligomerization of alkenes, in particular of isobutene or decene; esters of acids or of alcohols containing a linear alkyl group, more particularly plant oils, ethyl oleate, propylene glycol di-(caprylate/caprate), glyceryl tri-(caprylate/caprate) or propylene glycol dioleate; esters of branched fatty acids or alcohols, in particular isostearic acid esters. The oil is used in combination with emulsifiers to form the emulsion. The emulsifiers are preferably nonionic surfactants, in particular esters of sorbitan, of mannide (e.g. anhydromannitol oleate), of glycol, of polyglycerol, of propylene glycol and of oleic, isostearic, ricinoleic or hydroxystearic acid, which are optionally ethoxylated, and polyoxypropylene-polyoxyethylene copolymer blocks, in particular the Pluronic products, especially L121. See Hunter et al., The Theory and Practical Application of Adjuvants (Ed. Stewart-Tull, D. E. S.). John Wiley and Sons, NY, pp 51-94 (1995) and Todd et al., Vaccine 15:564-570 (1997).
[0021] For example, it is possible to use the SPT emulsion described on page 147 of "Vaccine Design, The Subunit and Adjuvant Approach" edited by M. Powell and M. Newman, Plenum Press, 1995, and the emulsion MF59 described on page 183 of this same book.
[0022] A further instance of an adjuvant is a compound chosen from the polymers of acrylic or methacrylic acid and the copolymers of maleic anhydride and alkenyl derivative. Advantageous adjuvant compounds are the polymers of acrylic or methacrylic acid which are cross-linked, especially with polyalkenyl ethers of sugars or polyalcohols. These compounds are known by the term carbomer (Phameuropa Vol. 8, No. 2, June 1996). Persons skilled in the art can also refer to U.S. Pat. No. 2,909,462 which describes such acrylic polymers cross-linked with a polyhydroxylated compound having at least 3 hydroxyl groups, preferably not more than 8, the hydrogen atoms of at least three hydroxyls being replaced by unsaturated aliphatic radicals having at least 2 carbon atoms. The preferred radicals are those containing from 2 to 4 carbon atoms, e.g. vinyls, allyls and other ethylenically unsaturated groups. The unsaturated radicals may themselves contain other substituents, such as methyl. The products sold under the name Carbopol (BF Goodrich, Ohio, USA) are particularly appropriate for compositions containing such adjuvants. They are cross-linked with an allyl sucrose or with allyl pentaerythritol. The dissolution of these polymers in water leads to an acid solution that will be neutralized, preferably to physiological pH, in order to give the adjuvant solution into which the immunogenic, immunological or vaccine composition itself will be incorporated.
[0023] Further suitable adjuvants include, but are not limited to, the RIBI adjuvant system (Ribi Inc.), Block co-polymer (CytRx, Atlanta Ga.), SAF-M (Chiron, Emeryville Calif.), monophosphoryl lipid A, Avridine lipid-amine adjuvant, heat-labile enterotoxin from E. coli (recombinant or otherwise), cholera toxin, IMS 1314 or muramyl dipeptide among many others.
[0024] Additionally, the composition can include one or more pharmaceutical-acceptable carriers. As used herein, "a pharmaceutical-acceptable carrier" includes any and all solvents, dispersion media, coatings, stabilizing agents, diluents, preservatives, antibacterial and antifungal agents, isotonic agents, adsorption delaying agents, and the like. Diluents can include water, saline, dextrose, ethanol, glycerol, and the like. Isotonic agents can include sodium chloride, dextrose, mannitol, sorbitol, and lactose, among others. Stabilizers include albumin and alkalisalts of ethylendiamintetracetic acid, among others.
[0025] A "protectant" or "preservative" as used herein, refers to an anti-microbiological active agent, such as for example Neomycin, Amphoteracin B, Gentamycin, Merthiolate, and the like. Of these, Neomycin and/or Amphoteracin B are particularly preferred In particular adding a protectant is most preferred for the preparation of a multi-dose composition. Those anti-microbiological active agents are added in concentrations effective to prevent the composition of interest from any microbiological contamination or for inhibition of any microbiological growth within the composition of interest.
[0026] Moreover, this method can also comprise the addition of any stabilizing agent, such as for example saccharides, trehalose, mannitol, saccharose and the like, to increase and/or maintain product shelf-life.
[0027] In preferred forms, administration of any vaccine composition noted above will be safe for the animal receiving the composition both before and during pregnancy. "Safe" as used herein, shall refer to a comparison in animals receiving the composition with animals not receiving the composition wherein the abortion rates of the vaccinated pregnant cows/heifers are less than 10% higher, more preferably less than 5% higher, still more preferably less than 4% higher, even more preferably less than 3% higher, still more preferably less than 2% higher, even more preferably less than 1% higher, and most preferably no higher than unvaccinated cows/heifers. Additionally, administration of any vaccine composition noted above to a pregnant cow/heifer will not cause fetal infection by any pathogen having an immunological active component in the vaccine in more than 10%, more preferably 5%, still more preferably 4%, even more preferably 3%, still more preferably 2%, even more preferably 1% and most preferably no higher than unvaccinated cows/heifers.
[0028] Thus according a further aspect the present invention also relates to method for the treatment or prophylaxis of a pregnant cow/heifer and its fetus against infections, or at least the clinical signs, caused by caused by BVDV comprising the step administering to said pregnant cow/heifer a vaccine comprising modified live live bovine viral diarrhea virus as described above. Preferably the live bovine viral diarrhea virus is a modified live BVDV Type 1 strain derived from the Singer strain and/or a modified live BVDV Type 2 derived from the 296 strain. Preferably the modified live BVDV Type 1 Singer strain is the one that is included in the BREED-BACK® FP5 vaccine. Preferably the modified live BVDV Type 2 296 strain is the one that is included in the BREED-BACK® FP5 vaccine. Representative vaccines are also sold under the names BREED-BACK® FP5-HS, EXPRESS® 5-HS, BREED-BACK® FP10-HS and EXPRESS 10-HS®.
[0029] According a further aspect, the present invention also relates to a method for the treatment or prophylaxis of pregnant cow/heifer and its fetus against infections, or at least the clinical signs, caused by IBR comprising the step administering to said pregnant cow/heifer a vaccine comprising modified live live IBR as described above. Preferably the modified IBR strain is the one that is included in the BREED-BACK® FP5 vaccine. Representative vaccines are also sold under the names BREED-BACK® FP5-HS, EXPRESS® 5-HS, BREED-BACK® FP10-HS and EXPRESS 10-HS®.
[0030] Thus according to a further aspect, the present invention also relates to method for the treatment or prophylaxis of a pregnant cow/heifer and its fetus against infections, or at least the clinical signs, caused by BVDV and IBR comprising the step administering to said pregnant cow/heifer a vaccine comprising modified live live bovine viral diarrhea virus and modified live IBR as described above. Preferably the live bovine viral diarrhea virus is a modified live BVDV Type 1 strain derived from the Singer strain and/or a modified live BVDV Type 2 derived from the 296 strain. Preferably the modified live BVDV Type 1 Singer strain is the one that is included in the BREED-BACK® FP5 vaccine. Preferably the modified live BVDV Type 2 296 strain is the one that is included in the BREED-BACK® FP5 vaccine. Preferably the modified IBR strain is the one that is included in the BREED-BACK® FP5 vaccine. Representative vaccines are also sold under the names BREED-BACK® FP5-HS, EXPRESS® FP5, EXPRESS® 5-HS, BREED-BACK® FP10-HS and EXPRESS 10-HS®.
[0031] In preferred methods of the present invention, pregnant cows/heifers receiving an administration of any of the vaccine compositions described above will experience "treatment or prophylaxis" in the form of a decrease or reduction in the incidence of or severity of clinical, pathological, and histopathological signs of infection from any of the pathogens having an immunological active component included in the administered vaccine. "Decrease" or "reduction in the incidence of or severity of clinical, pathological, and/or histopathological signs" shall mean that clinical signs are reduced in incidence or severity in animals receiving an administration of the vaccine in comparison with a "control group" of animals when both have been infected with or challenged by the pathogen from which the immunological active component(s) in the vaccine are derived and wherein the control group has not received an administration of the vaccine. In this context, the term "decrease" or "reduction" means a reduction of at least 10%, preferably 25%, even more preferably 50%, most preferably of more than 100% in the vaccinated group as compared to the control group as defined above.
[0032] "Clinical signs" shall refer to signs of infection from a pathogen that are directly observable from a live animal such as symptoms. Representative examples will depend on the pathogen selected but can include things such as nasal discharge, lethargy, coughing, elevated fever, weight gain or loss, dehydration, diarrhea, swelling, lameness, and the like.
[0033] "Pathological" signs shall refer to signs of infection that are observable at the microscopic or molecular level, through biochemical testing, or with the naked eye upon necropsy.
[0034] "Histopathological" signs shall refer to signs of tissue changes resulting from infection. Administration of any of the vaccine compositions described herein can occur in any conventional manner or fashion known in the art with intramuscularly and subcutaneously being particularly preferred, and with subcutaneous administration being the most preferred.
[0035] In another aspect of the present invention, a method of treatment or prophylaxis of pregnant cows or heifers of clinical signs or symptoms of infection caused by bovine viral diarrhea virus is provided. Generally, the method comprises the step of administering an immunogenic composition to a pregnant cow/heifer, wherein the immunogenic composition comprises a modified live bovine viral diarrhea virus. Preferably the live bovine viral diarrhea virus is a modified live BVDV Type 1 strain derived from the Singer strain and/or a modified live BVDV Type 2 derived from the 296 strain. Preferably the modified live BVDV Type 1 Singer strain is the one that is included in the BREED-BACK® FP5 vaccine. Preferably the modified live BVDV Type 2 296 strain is the one that is included in the BREED-BACK® FP5 vaccine. Representative vaccines are also sold under the names BREED-BACK® FP5-HS, EXPRESS® 5-HS, BREED-BACK® FP10-HS and EXPRESS 10-HS®. In preferred forms, the immunogenic composition, routes of administration, timing of administration, and variations noted above in describing the vaccine compositions are the same for the immunogenic composition and methods of this aspect.
[0036] In another aspect of the present invention, the vaccine or immunogenic composition as described herein is administered to healthy susceptible cows and replacement heifers prior to breeding wherein such administration prevents persistently infected calves due to BVD Types 1 and 2.
[0037] In another aspect of the present invention, the vaccine or immunogenic composition as described herein aids in the reduction of respiratory diseases caused by IBR virus, BVDV Types 1 and 2, PI-3 virus, and BRSV when administered to pregnant females or calves nursing pregnant females that had been vaccinated with the same vaccine or immunogenic composition prior to breeding or being artificially inseminated. In preferred forms of this aspect, for cows and heifers and using aseptic techniques, annually inject a 2 mL dose intramuscularly or subcutaneously at or about four weeks prior to breeding. Pregnant cows and nursing calves may be vaccinated following the pre-breeding vaccination.
[0038] For the aspects of the invention described herein, attenuated modified live BVDV Type 1 and 2 strains are grown in MDBK-cells until a TCID50 of about 105.0 to 108.1 per ml cell culture fluid. A modified live attenuated strain of IBR is grown in MDBK cells until a TCID50 of about 105.0 to 108.6 per ml cell culture fluid. A live attenuated strain of BRSV is grown in MDBK cells until a TCID50 of about 105.0 to 107.2 per ml cell culture fluid. A live attenuated strain of PI-3 is grown in MDBK cells until a TCID50 of about 104.2 to 106.5 per ml cell culture fluid. Leptospira bacterium, and especially those described above, are separately cultivated until reaching 108.0 to 1011.0 cells per ml culture. The bacteria cultures are inactivated and the culture fluids are lyophilized or freeze dried. H. somnus is cultivated until achieving 107.1 to 109.2 cells per ml culture. The bacteria culture is inactivated and the culture fluid is lyophilized or freeze dried.
[0039] For any of the vaccine compositions described herein, final dosage amounts for the individual components is as follows: IBR (105.0 to 108.6 TCID50), BVDV-1 (105.0 to 108.1 TCID50), BVDV-2 (105.0 to 108.1 TCID50), BRSV (105.0 to 107.2 TCID50), PI3 (104.2 to 106.5 TCID50), each selected Leptospira bacteria 108.0 to 1011.0 cells per ml culture, and Haemophilus somnus 107.1 to 109.2 cells per ml culture. Still more preferably, the dosage amounts are as found in a product selected from the group consisting of BREED-BACK® 5, EXPRESS® 5, BREED-BACK® FP5, EXPRESS® FP5, BREED-BACK® 5HS, EXPRESS® 5HS, BREED-BACK® FP5-HS, EXPRESS® FP5-HS, BREED-BACK® 10, EXPRESS® 10, BREED-BACK® FP10, EXPRESS® 10, BREEDBACK® FP10-HS, EXPRESS FP10-HS®, BREED-BACK® 10HS, EXPRESS® FP3-VL5, and EXPRESS® FP5-VL5. It is noted that the BREED-BACK product line has been replaced by the EXPRESS product line. However, this change was in name only as all components therein remained the same.
Further Definitions:
[0040] It must be noted that as used herein and in the appended claims, the singular forms "a", "an", and "the" include plural reference unless the context clearly dictates otherwise. Thus, for example, reference to "a BVDV" includes a plurality of such BVDV, reference to the "cell" is a reference to one or more cells and equivalents thereof known to those skilled in the art, and so forth. Unless defined otherwise, all technical and scientific terms used herein have the same meanings as commonly understood by one of ordinary skill in the art to which this invention belongs. Although any methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention, the preferred methods, devices, and materials are now described. All publications mentioned herein are incorporated herein by reference in their entireties including for the purpose of describing and disclosing the cell lines, vectors, and methodologies as reported in the publications, which might be used in connection with the invention. Nothing herein is to be construed as an admission that the invention is not entitled to antedate such disclosure by virtue of prior invention.
[0041] The term "BVDV" as used herein refers to all viruses belonging to species bovine viral diarrhea virus (BVDV) type 1 (BVDV-1) and BVDV type 2 (BVDV-2), including any sub-species such as 1a, 1b, 2a, 2,b, and the like in the genus Pestivirus within the family Flaviviridae (Heinz et al., 2000). The more classical BVDV type 1 strains and the more recently recognized BVDV type 2 strains display some limited but distinctive differences in nucleotide and amino acid sequences. Preferably the term BVDV as used herein refers to the modified BVDV. Even more preferably the modified BVDV as used herein refers to a cytopathic modified live BVDV Type 1 strain derived from the Singer strain and/or a cytopathic modified live BVDV Type 2 derived from the 296 strain. Preferably the modified live BVDV Type 1 Singer strain refers to the one that is included in the BREED-BACK® FP5 vaccine. Preferably the modified live BVDV Type 2 296 strain refers to the one that is included in the BREED-BACK® FP5 vaccine.
[0042] "A modified live BVDV" as used herein means that there is a statistically significant difference between the virulence of modified live BVDV of the present invention, and wild-type BVDV isolates including those from which said modified live BVDV have been derived, for the predominant clinical parameters, in case of BVDV for diarrhea, pyrexia and lethality in animals infected with the same dose, which may be 6×106 TCID50. Thus, said modified live BVDV have a reduced incidence of or severity of clinical, pathological, and histopathological signs associated with BVDV infection, including diarrhea, pyrexia and lethality.
[0043] "Immunological active component" or "immunologically active component" as used herein means a component that induces or stimulates the immune response in an animal to which said component is administered. Said immune response may be directed to said component or to a microorganism comprising said component. The immunological active component may be an attenuated microorganism, including modified live virus (MLV), a killed-microorganism or at least an immunological active part of a microorganism.
[0044] "Immunological active part of a microorganism" as used herein means a protein-, sugar-, and or glycoprotein containing fraction of a microorganism that comprises at least one antigen that induces or stimulates the immune response in an animal to which said component is administered. Said immune response may be directed to said immunological active part of a microorganism or to a microorganism comprising said immunological active part.
[0045] The term "vaccine" as used herein refers to a pharmaceutical composition comprising at least one immunologically active component that induces an immunological response in an animal and possibly, but not necessarily, one or more additional components that enhance the immunological activity of said active component. A vaccine may additionally comprise further components typical to pharmaceutical compositions. The immunologically active component of a vaccine may comprise complete virus particles in either their original form or as attenuated particles in a so-called modified live vaccine (MLV) or particles inactivated by appropriate methods in a so-called killed vaccine (KV). In another form, the immunologically active component of a vaccine may comprise appropriate elements of said organisms (subunit vaccines) whereby these elements are generated either by destroying the whole particle or the growth cultures containing such particles and optionally, subsequent purification steps yielding the desired structure(s), or by synthetic processes including an appropriate manipulation by use of a suitable system based on, for example, bacteria, insects, mammalian or other species, plus optionally subsequent isolation and purification procedures, or by induction of said synthetic processes in the animal needing a vaccine by direct incorporation of genetic material using suitable pharmaceutical compositions (polynucleotide vaccination). A vaccine may comprise one or simultaneously more than one of the elements described above. The term "vaccine" as understood herein is a vaccine for veterinary use comprising antigenic substances and is administered for the purpose of inducing a specific and active immunity against a disease provoked by a microbiological infection, such as by a BVDV infection. The BVDV as described herein, confer active immunity that may be transferred passively via maternal antibodies against the immunogens it contains and sometimes also against antigenically related organisms. A vaccine of the invention refers to a vaccine as defined above, wherein one immunologically active component is a BVDV or derived from a nucleotide sequence that is more than 70% homologous to any known BVDV sequence (sense or antisense).
[0046] The term "live vaccine" refers to a vaccine comprising a replication competent, in particular, a replication compentent viral active component.
[0047] A "pharmaceutical composition" essentially consists of one or more ingredients capable of modifying physiological e.g. immunological functions of the organism it is administered to, or of organisms living in or on the organism. The term includes, but is not restricted to, antibiotics or antiparasitics, as well as other constituents commonly used to achieve certain other objectives like, but not limited to, processing traits, sterility, stability, feasibility to administer the composition via enteral or parenteral routes such as oral, intranasal, intravenous, intramuscular, subcutaneous, intradermal or other suitable route, tolerance after administration, and controlled release properties. One non-limiting example of such a pharmaceutical composition, solely given for demonstration purposes, could be prepared as follows: Cell culture supernatant of an infected cell culture is mixed with a stabilizer (e.g. spermidine and/or BSA (bovine serum albumin)) and the mixture is subsequently lyophilized or dehydrated by other methods. Prior to vaccination, said mixture is then rehydrated in aqueous (e.g. saline, PBS (phosphate buffered saline)) or non-aqueous solutions (e.g. oil emulsion, aluminum-based adjuvant).
EXAMPLE
[0048] The following example serves to further illustrate the present invention; but the same should not be construed as limiting the scope of the invention disclosed herein.
Example 1
Safety of Administering IBR, BVD1, BVD2, PI3, and BRSV Combination Virus Vaccine to Pregnant Cows and their Calves
1. Summary
[0049] The objective of this study was to demonstrate the safety of modified live Infectious Bovine Rhinotracheitis (IBR) and Bovine Viral Diarrhea (BVD) Type 1 and 2 vaccine components as part of booster vaccines for use in previously vaccinated first, second and third trimester pregnant cows and heifers. The study monitored the following primary parameters: Pregnancy outcome from all three trimesters and post-natal health of the calves; Pre-colostral serological status of selected calves from the second and third trimesters.
[0050] Cows and heifers from three cow/calf ranches in north-central Nebraska were enrolled to determine calving outcome and calf health status. Cows from a cow/calf ranch in Alberta Canada were also enrolled.
[0051] a. Nebraska Sites:
[0052] For the Nebraska sites, all cows and heifers were given a pre-breeding vaccination of 10-way vaccine (IBR, BVD 1, BVD 2, PI3, BRSV MLV rehydrated with 5-way Leptospira bacterin) (BREED-BACK® FP10) one to two months prior to breeding. Booster vaccinations (Test vaccine Group A, 10-way vaccine (BREED-BACK® FP10), Product Code 4469.23 or Placebo vaccine Group B, 5-way Leptospira bacterin, Product Code 2665.00) were administered to the cows and heifers, with the timing of administration based upon trimester assignment. Pregnancy status was confirmed prior to the booster vaccination, with the pregnant cattle randomly assigned to either Group A or Group B. Cows and heifers located at the Raymond ranch, along with a supplemental set of cows from the A&K ranch, were revaccinated during the first trimester. Cows and heifers located at the A&K ranch were assigned to vaccination during the second trimester. Cows and heifers located at the Williams ranch were assigned to vaccination during the third trimester.
[0053] All cows and heifers were followed through calving and the calving outcome recorded for each case. Calving outcome was recorded as either Open (heifer or cow diagnosed as not pregnant, with no calf), Dead (calving resulted in a dead calf not diagnosed as dystocia), or Live (calving resulted in a live calf diagnosed as normal at calving). Calves that died at or immediately after calving due to calving difficulties (dystocia), weather related deaths (frozen in blizzard) or other non-study related causes (calf crushed when stepped on by dam) were removed from the trial. The animals that were removed were not included in the final study results. The Open and Dead cases were combined under the category Fetal Losses.
[0054] The resulting calves were observed for four weeks postpartum. The postpartum treatment rates and deaths were recorded.
[0055] The results of the study are summarized as follows: For First Trimester Group A, 306 cows/heifers qualified for enrollment and there were 7 fetal losses for a 2.3% loss rate; For First Trimester Group B, 274 cows/heifers qualified for enrollment and there were 6 fetal losses for a 2.2% loss rate. For Second Trimester Group A, 237 cows/heifers qualified for enrollment and there was 1 fetal loss for a 0.4% loss rate; For Second Trimester Group B, 235 cows/heifers qualified for enrollment and there were 3 fetal losses for a 1.3% loss rate. For Third Trimester Group A, 267 cows/heifers qualified for enrollment and there were 5 fetal losses for a 1.9% loss rate; For Third Trimester Group B, 267 cows/heifers qualified for enrollment and there were 6 fetal losses for a 2.2% loss rate.
[0056] A full necropsy was performed on all available fetuses (including dystocia, hypothermia, etc. cases). Tissues and body fluid samples, as available, were submitted to the Animal Disease Research & Diagnostic (ADRD) Laboratory, South Dakota State University for analysis. Tests specific for detection of Infectious Bovine Rhinotracheitis (IBR) and Bovine Viral Diarrhea Virus (BVD) were performed. In addition, Rural Technologies Inc. (RTI) performed virus isolations on all submitted tissues. All tests for viral detection and isolation on all fetal tissues were negative.
[0057] Heart blood and other body fluids, as available at necropsy, were tested for antibody to IBR, BVD 1 and BVD 2 by the ADRD laboratory. There were a total of six fetuses that tested positive for antibody, however, due to either site practices (forced feeding of colostrum) or testing problems due to sample toxicity/contamination resulting in the lack of confirmation of the test results, these results did not impact the outcome of the study.
[0058] Post-calving observations showed that the enrolled calves had low treatment and death rates. Treatments were necessary in the second and third trimester herds due to a mild outbreak of scours. The observations indicated that the majority of cases cleared in 24 to 48 hours. Few post calving deaths occurred. Necropsy results were negative for virus pathogens in the post calving deaths.
[0059] b. Alberta Site:
[0060] The trial to examine criteria was performed at a cow/calf ranch near Fort Macleod in south central Alberta, Canada. Cows that had been vaccinated pre-breeding were given booster vaccinations in either the second or third trimester. Valid pre-colostral blood samples were successfully taken from a total of 61 calves from the second trimester vaccinated cows and from 59 calves in the third trimester cows. All valid pre-colostral serum samples tested negative for antibody to IBR, BVD 1 and BVD 2. In addition, all serum samples were tested for IBR virus by virus isolation and for BVD 1 and 2 by RT PCR. All serum samples were negative for the presence of virus.
2. Final Results
[0061] The results of this study have shown no indication that vaccination of previously vaccinated pregnant cattle in the first, second or third trimester with the modified live IBR and BVD Type 1 and 2 components would result in deleterious effects to either the pregnant cow/heifer or the calves.
3. Introduction
[0062] Combination vaccines containing modified live virus (MLV) IBR and modified live BVD Types 1 and 2 have been developed and registered for use in cattle. Efficacy trials have proven the IBR, BVD 1 and BVD 2 combination vaccines (Express® and Breed-Back FP 5®, Bovine Rhinotracheitis-Viral Diarrhea-Parainfluenza3-Respiratory Syncytial Virus Vaccine, Modified Live Virus, and combinations; Boehringer Ingelheim Vetmedica) to be effective in preventing BVD Type 1 and 2 persistent fetal infection when administered prior to breeding. Due to safety issues with the use of the IBR and BVD viruses in naive pregnant cattle, these conventionally attenuated virus vaccines have label warnings against the use of the vaccines in pregnant cattle or in calves nursing pregnant cattle. To remove these warnings from the labels for products which contain the same modified live IBR and BVD 1 and BVD 2 components, safety studies were completed in pregnant cattle.
4. Objectives
[0063] The objectives of this study were to perform a field safety trial in order to determine the pregnancy outcome in pregnant cows and heifers when vaccinated prior to breeding and subsequently vaccinated in the first, second or third trimester of pregnancy with a product containing the IBR and BVD Types 1 and 2 components of BIVI fetal protection product; to determine the health of the calves born to the enrolled cows and heifers by post-partum observations for a total of four weeks; and determine pre-colostral serological status for IBR, BVD 1, BVD 2 in calves born from cows and heifers vaccinated in the second and third trimester of pregnancy.
[0064] The results of this study provides proof of safety of the use of the modified live viral products containing IBR and BVD 1 and BVD 2 components and permit revision of the labeled safety precautions regarding use of the vaccines in previously vaccinated pregnant cattle and in calves nursing pregnant cattle.
5. Materials and Methods
[0065] a. Start of Study:
[0066] Nebraska:
[0067] The study was considered to be officially started on Day 0 for the first trimester herd enrollment pregnancy check/vaccination which was performed on Day 0. However, the pre-breeding vaccinations for the enrolled cattle started on Day -140, with the first vaccinations occurring in the Raymond herd.
[0068] Alberta:
[0069] The study was considered to be officially started on Day 0 for the vaccination of Group 1, Third Trimester.
[0070] b. End of Study:
[0071] Nebraska:
[0072] The animal portion of the study was completed with the final observation of the calves on Day 295. The laboratory portion of the study ended on Day 399 with receipt of the final BVD serology testing results from Benchmark BioLabs Inc.
[0073] Alberta:
[0074] The animal portion of the study was completed with the sampling of the final calf on Day 433. The laboratory portion of the tests was completed between Day 487 and Day 517.
6. Study Design
[0075] a. General Description:
[0076] This large field safety study was designed to determine the safety of the administration of vaccines containing MLV IBR and BVD 1 and 2 components to previously vaccinated pregnant cows and heifers. This trial consisted of two separate segments, the first being a large field safety trial, conducted in Nebraska that investigated calving outcome and post-partum calf health. The second segment, conducted in Alberta, Canada, involved vaccinations of previously vaccinated pregnant cattle in the second and third trimesters, and obtaining pre-colostral serum samples to determine levels of antibody to IBR and BVD 1 and BVD 2. The Nebraska treatment groups are outlined in Tables B, C, and D and the Alberta Canada treatment groups are outlined in Tables E and F.
TABLE-US-00001 TABLE B General Trial Design, Nebraska First Trimester MINIMUM NUMBER TREAT- VACCI- MENT 1 TREAT- GROUP SUBGROUP NATED (Pre-Breeding) MENT 2 First Group A MLV 200 IBR-BVD1- IBR-BVD1- Trimester Vaccine BVD2-PI3- BVD2-PI3- Vaccinates BRSV MLV, BRSV MLV, LEPTO 5 LEPTO 5 Group B 200 IBR-BVD1- Lepto 5 Placebo BVD2-PI3- Bacterin Controls BRSV MLV, LEPTO 5
TABLE-US-00002 TABLE C General Trial Design, Nebraska Second Trimester MINIMUM NUMBER TREAT- VACCI- MENT 1 TREAT- GROUP SUBGROUP NATED (Pre-Breeding) MENT 2 Second Group A MLV 200 IBR-BVD1- IBR-BVD1- Trimester Vaccine BVD2-PI3- BVD2-PI3- Vaccinates BRSV MLV, BRSV MLV, LEPTO 5 LEPTO 5 Group B 200 IBR-BVD1- Lepto 5 Placebo BVD2-PI3- Bacterin Controls BRSV MLV, LEPTO 5
TABLE-US-00003 TABLE D General Trial Design, Nebraska Third Trimester MINIMUM NUMBER TREAT- VACCI- MENT 1 TREAT- GROUP SUBGROUP NATED (Pre-Breeding) MENT 2 Third Group A MLV 200 IBR-BVD1- IBR-BVD1- Trimester Vaccine BVD2-PI3- BVD2-PI3- Vaccinates BRSV MLV, BRSV MLV, LEPTO 5 LEPTO 5 Group B 200 IBR-BVD1- Lepto 5 Placebo BVD2-PI3- Bacterin Controls BRSV MLV, LEPTO 5
TABLE-US-00004 TABLE E General Trial Design, Alberta Second Trimester MINIMUM NUMBER TREAT- VACCI- MENT 1 TREAT- GROUP SUBGROUP NATED (Pre-Breeding) MENT 2 Second MLV 65 IBR-BVD1- IBR-BVD1- Trimester Vaccine BVD2-PI3- BVD2-PI3- Vaccinates BRSV MLV BRSV MLV
TABLE-US-00005 TABLE F General Trial Design, Alberta Third Trimester MINIMUM NUMBER TREAT- VACCI- MENT 1 TREAT- GROUP SUBGROUP NATED (Pre-Breeding) MENT 2 Third Group A MLV 65 IBR-BVD1- IBR-BVD1- Trimester Vaccine BVD2-PI3- BVD2-PI3- Vaccinates BRSV MLV BRSV MLV
[0077] b. Nebraska Sites:
[0078] Trial Sites:
[0079] Three working cow-calf production ranches located in the rural Ainsworth/Johnstown Nebraska area were identified as having normally low (between 3 to 5%) calving losses. The chosen ranches did not have recent history of either IBR or BVD abortions. With the exception of 82 additional cows enrolled in the first trimester, each trimester consisted of animals from a single herd. Parity of the animals enrolled varied from first calf heifers up to cows with histories of 10 or more pregnancies.
[0080] Cows and heifers at the Raymond/Finney Ranch (included Raymond and Walking Y Ranch cows and heifers) were enrolled in the study as first trimester test animals. In addition, a portion of the cows from the A&K herd were also enrolled as first trimester test animals.
[0081] Cows and heifers at the A&K Ranch were enrolled in the study as second trimester test animals.
[0082] Cows and heifers at the Williams & Williams (W&W) Ranch were enrolled in the study as third trimester test animals.
[0083] Animal Selection and Identification:
[0084] All heifers and cows enrolled into the study were physically normal, healthy breeding age female Angus or Angus-cross beef cattle. To prevent enrollment of BVD persistently infected (PI) cattle, all heifers in all three herds were ear notched prior to enrollment. Similarly, the calves of the cows of that year available for enrollment were ear notched. The ear notch samples were submitted to the University of Nebraska Veterinary Diagnostic Laboratory (UNVDL), Lincoln, Nebr. for testing by immunohistochemistry. The semen from bulls used for breeding or the semen used for artificial insemination was tested for the presence of BVD by PCR at UNVDL. In addition, all bulls used for breeding were ear notched.
[0085] All enrolled heifers and cows were identified using one or two plastic ear tags, a metal Nebraska state ear tag and an electronic identification device (EID). All forms of identification were confirmed each time the animal was handled. Any missing identification was replaced.
[0086] A total of two thousand sixty-three (2,063) cows/heifers completed the pre-breeding vaccinations which occurred between Day -140 and Day -67. Six hundred ten (610) cows/heifers were vaccinated for the first trimester (T1). Seven-hundred seven (707) cows/heifers were vaccinated for the second trimester (T2). Seven-hundred forty-six (746) cows/heifers were vaccinated for the third trimester (T3). These animals were bred and pregnancy checked just prior to the trimester enrollment vaccination. The number of animals available for enrollment at the time of trimester vaccinations was reduced from the initial number due to normal expected losses that included non-pregnant (open) animals, lameness, lightning strikes, etc.
[0087] Animal Management and Housing:
[0088] All three herds were managed according to their normal husbandry practices, with the exception that cows/heifers from Treatment Group A and Treatment Group B were housed as separate groups (no nose to nose contact between Groups A and B) for a minimum of 30 days after the assigned trimester vaccination. In each case, initial housing was located at the home pastures.
[0089] In the case of the A&K cows that were assigned to T1, the 82 cows were separated from the remaining A&K herd for 30 days after the T1 vaccination, after which the cows were allowed to rejoin the main A&K cow herd. Once again, at the time of the T2 vaccination, the cows/heifers enrolled in Treatment Group A were isolated from the remainder of the herd for 30 days.
[0090] All herds were fed according to their normal herd practices, as appropriate for age, weight, and pregnancy status. All heifers and cows enrolled in the study were pastured according to a rotation schedule determined by each producer throughout the trial. This included movement of the herd to corn stock pastures for the winter months. Details, including area maps for each herd, are filed with the raw data for the study. Feed for the heifers and cows were supplemented with a protein and mineral supplement (cake) and ground hay during the winter months as deemed necessary by each producer. All rations and supplements were pre-approved by the Investigators and Study Monitor.
[0091] Daily herd observations were performed starting on Day -123 and continued through Day 280 for T1, Day 276 for T2 and Day 295 for T3 at which time all enrolled calves were at least 30 days of age. Any abnormalities or other observations or comments were recorded in the notes section of the Clinical Assessment Forms. These are included in the raw data files for the study.
[0092] Breeding:
[0093] T1 and T3 trial sites used bull breeding. For T2, the heifers and majority of the cows were artificially inseminated, followed by the use of clean up bulls.
[0094] Enrollment Pregnancy Checks:
[0095] The Raymond/Finney heifers for T1 were ultrasounded for verification of pregnancy status on Day 0. Sixty-one (61) heifers were determined to be between 40 to 70 days of gestation. Cows from the Raymond/Finney herd for T1 were ultrasounded for verification of pregnancy status on Day 14 and Day 15. A total of 458 cows were determined to be between 40 to 70 days gestation and eligible for enrollment in the trial.
[0096] The A&K cows enrolled as T1 on Day 16 had been ultrasounded on Day -4 and determined to be between 40 and 70 days of gestation.
[0097] The A&K heifers for enrollment in T2 were ultrasounded for verification of pregnancy on Day -6. At that time, 95 heifers were determined to be between 40 to 70 days gestation.
[0098] The A&K cows were ultrasounded on Days -5, -4, -1, and 1 for verification of pregnancy status. At that time, 476 cows were determined to be between 40 to 70 days gestation. As noted above, 82 of the animals ultrasounded on Day -4 were enrolled as T1 animals on Day 16.
[0099] All A&K cows and heifers determined to be pregnant and within the gestation window required for enrollment in the study were palpated to confirm pregnancy status immediately prior to vaccination enrollment on Day 79 for the heifers and on Days 92 and 93 for the cows. Animals determined to be open or to have health issues at that time were not enrolled in the trial.
[0100] The W&W heifers for enrollment in T3 were initially ultrasounded on Day 13. At that time, 132 heifers were determined to be between 40 and 70 days gestation.
[0101] The W&W cows for enrollment in T3 were initially ultrasounded on Days 28, 29, and 30. At that time, 428 were determined to be between 40 to 70 days gestation.
[0102] The W&W cows and heifers determined to be pregnant and within the gestation window required for enrollment in the study were palpated to confirm pregnancy status immediately prior to vaccination enrollment on Day 177 for the heifers and on Days 196 and 197 for the cows. Animals determined to be open or have health issues at that time were not enrolled in the trial.
[0103] Randomization:
[0104] The T1 Raymond heifers, T1 A&K cows, T2 A&K cows and heifers, and the T3 W&W cows and heifers were assigned to treatment group A or B utilizing randomization software. For each set of vaccinations, two series of random numbers were generated. If the higher random number was listed in the first column of numbers, the assignment was to Group A. If the higher random number was in the second column of numbers, the assignment was to Group B. The heifer or cow was then allotted to the next assigned treatment group on the spreadsheet as the animals were worked through the chute. In the case that all slots on the spreadsheet were not used or additional group assignments were necessary, the last few animals coming through the chute were randomized to group based upon coin toss.
[0105] For the T1 cows, these animals were housed in two separate but adjacent pastures. Assignment of the pasture as a group to Treatment A or B was done by coin toss.
[0106] Enrollment Vaccinations:
[0107] The Test Vaccine (IBR, BVD 1 BVD Type 2, PI3, BRSV, Lepto 5 Serial #MK-270A or MK-270B) was administered to the cows and heifers enrolled in Treatment A. The Placebo Vaccine (Lepto 5 Bacterin, Serial Number 184-089) was administered to the cows and heifers enrolled in Treatment B. Lepto 5 Bacterin contains all of the Leptospira strains, Leptospira canicola, Leptospira grippotyphosa, Leptospira hardjo, Leptospira icterohaemorrhagiae, and Leptospira Pomona, as are found in the EXPRESS® and BREED-BACK® products including, but not limited to EXPRESS® 10, BREEDBACK® 10, BREEDBACK® FP10, and EXPRESS® FP10. The use of this placebo was a deviation to the protocol. The protocol stated that the placebo would be sterile water.
[0108] T1 Vaccinations:
[0109] On Days 0, 14, and 15, 61 heifers, 244 cows and 214 cows, respectively, from the Raymond/Finney herd were determined to meet the enrollment criteria for pregnancy status. These heifers and cows were bled and the assigned vaccine product was administered according to the randomization process. On Day 16, 82 additional cows from the A&K herd were administered appropriate vaccine product or placebo based upon the assigned group. The pregnancy checks for the 82 A&K cows were performed on Day -4, which was a deviation to the protocol which stated that the pregnancy checks would be performed within 7 days of the enrollment vaccination. The mean gestation day for T1 enrollment was approximately 55, with an estimated range between 40-75 days gestation.
[0110] T2 Vaccinations:
[0111] On Days 79, 92, and 93, 90 heifers, 200 cows and 189 cows, respectively, from the A&K herd were determined to meet the enrollment criteria for pregnancy status. These heifers and cows were bled and the assigned vaccine product or placebo was administered according to the randomization process. The mean gestation day for T2 enrollment was approximately 140, with an estimated range between 120-160 days gestation.
[0112] T3 Vaccinations:
[0113] On Days 177, 196, and 197, 126 heifers, 251 cows and 166 cows, respectively, from the W&W herd were determined to meet the enrollment criteria for pregnancy status. These heifers and cows were bled and the assigned vaccine product or placebo was administered according to the randomization process. The mean gestation day for T3 enrollment was approximately 210, with an estimated range between 195-225 days gestation.
[0114] Pregnancy Outcome and Post-Calving Observations:
[0115] All enrolled animals were followed through to calving. Calving results were recorded on the Calving Record Form. All trimester enrolled animals diagnosed as pregnant at the trimester vaccination and determined to be open at the end of the trial were counted as a fetal loss. Cows and heifers diagnosed as open were bled at the time of diagnosis and 1 to 4 weeks later. The protocol originally stated that the paired samples would be taken two weeks apart. The serum sample taken at the time of the trimester enrollment vaccination as well as the paired serum samples taken after fetal loss were all tested for levels of serum neutralizing antibody to IBR, BVD Type 1 and BVD Type 2 to determine if serum antibody levels had increased significantly between the first and second of the paired samples, which could indicate a potential fetal loss due to one of the agents.
[0116] Deaths at or just after calving diagnosed as due to dystocia (calving difficulties) were removed from the study. Deaths due to other causes unrelated to the study, such as deaths due to hypothermia, dam inflicted injuries or broken limbs were also removed from the study. However, fetuses and calves that died due to dystocia, hypothermia or injuries were subjected to necropsy and testing. The following tissues (if sampling was possible) were collected from the necropsied fetuses: lung, thymus, brain (cerebellum), liver, kidney, spleen, placenta, stomach contents, heart blood and pleural fluid.
[0117] The calves were observed daily for four weeks following birth. Any observed health problems or required treatments were recorded.
[0118] Diagnostic Testing:
[0119] Tissue samples were submitted to a laboratory for testing. Tests performed included general histology, fluorescent antibody (FA) tests specific for IBR and BVD, Leptospira FA, aerobic culture, mycology culture and serum neutralization for IBR, BVD 1 and BVD 2. When obtained, fetal and post-calving ear notch samples were submitted to the laboratory for BVD immunohistochemistry testing.
[0120] Tissue samples were also submitted to RTI for performance of virus isolations in tissue culture specific for IBR and BVD.
[0121] Serum Neutralization Tests on Adult Serum Samples:
[0122] Serum neutralization assays specific for antibody to IBR on blood samples taken from the adult heifers and cows were performed by Benchmark BioLabs, Lincoln, Nebr. according to a standard procedure for serum neutralization. Serum neutralization assays specific for antibody to BVD Type 1 and BVD Type 2 on blood samples taken from the adult heifers and cows were performed by Boehringer Ingelheim Vetmedica Research and Development according to the standard procedure for Serum Neutralization.
[0123] Additional Non-Study Related Treatments Administered to the Enrolled Animals:
[0124] Additional treatments administered to the trimester enrolled animals included the following Ivomec® Pour-On (Merial), Guardian® Scour Vaccine (Schering-Plough Animal Health), administered to the cows and heifers, and Alpha 7® Clostridial Bacterin (Boehringer Ingelheim Vetmedica) administered to the calves.
[0125] c. Alberta Site:
[0126] General Design and Sample Collection:
[0127] This was a controlled field safety study involving two groups of cross-bred beef cows. The study was designed to determine the safety of the administration of MLV vaccines containing IBR and BVD1 and BVD2 to previously vaccinated pregnant cattle. The two groups of cows were located on a ranch near Fort Macleod, Alberta Canada. One group of cows was vaccinated in trimester three and the second group was vaccinated in trimester two. Each of the trimester groups was considered to be a separate trial, with the data summarized separately. All cows were bred by natural service at pasture.
[0128] After confirmation of pregnancy by rectal palpation, a group of one hundred twenty cross-bred beef cows was vaccinated with the modified live 5-way vaccine (IBR, BVD 1, BVD 2, PI3 and BRSV, APHIS product code 1181.24) in trimester three. A second group of one hundred and forty cross-bred beef cows was vaccinated with the 5-way MLV vaccine rehydrated with Lepto bacterin in trimester two. Based on the VSM guideline, it was not necessary to include a placebo group.
[0129] At the time of trimester enrollment vaccination of Group 1 (third trimester vaccination), the cows were also vaccinated with an inactivated Rotavirus/Coronavirus/E coli vaccine. This vaccine was administered as a separate shot in a separate site on the cow and had no affect on the outcome of the study. Following vaccination, each group of cows was housed either in a yard, at the ranch or pastured on range land. Each group of cows was observed daily to check for visual signs of fetal loss or other health problems. The investigator maintained a record of outcome of the pregnancy of all vaccinated cows in a calving record book as well as a daily activity calendar log.
[0130] Calves from 65 cows in group 1 and from 67 cows in group 2 were bled shortly after birth to obtain a pre-colostrum sample. If the investigator was unsure but suspected that a calf had suckled colostrum, the investigator did obtain a serum sample from the calf for testing and a note was made either in the in the calving record book or in the daily activity calendar. These calves were also indicated in the Investigator's "Research Data" calving/sampling spread sheet record for each study year.
[0131] Animal Selection and Identification:
[0132] Cattle selected for enrollment were physically normal, healthy breeding age female bovine, either cows or heifers. This herd had no history of infertility and no history of IBR and/or BVD related reproductive problems.
[0133] All cattle were identified with a unique number, using a plastic and/or metal ear tags. Calves were assigned a unique identification number and tagged, with a single tag, at birth based on the tag colour and on the sequence of it birth. The calf's tag was linked to the number of its dam in the calving records. In each of groups 1 and 2, all the cows received the same vaccination treatment. All calving events were observed except for the 2 fetal losses in Group 2 listed in "Calving Outcome" in the Results section below. The investigator selected calves born to cows from each group for serum collection based on his confidence that a calf was sampled before it suckled colostrum, with an objective to collect samples from at least 65 calves from each group. If the investigator was unsure that a calf had suckled, this was noted either in the "Remarks" section of the calving record book and/or in the calendar log of daily activities. Those calves were also indicated in the "Research Data" calving/sampling spread sheet record attached to the investigator's report for each study year.
[0134] Calving Records:
[0135] The investigator maintained a herd book for each of the two groups as well as a daily calendar log containing activities as part of the routine management of the herd. In addition to the identification of the dam, the date of birth and sex of the calf were recorded. These records also contain any notations applicable to herd health. To assist in herd management, a note on calving ease was made using a numeric scale (1 to 4), the calf's birth weight was estimated and the likely sire was also recorded. In the first year's calving season, the herd record book suggests a different, letter-based, scoring system for calving ease, but, for consistency, the numeric scale that had been used in the first year was used in the second year.
[0136] The record forms that were attached as a part of the study protocol were not used to record the results of the study. The investigator instead kept written records of the study in calving record books and daily activity logs. This is a deviation to the protocol, however, it did not affect the outcome of the study.
[0137] Serum Neutralization and Polymerase Chain Reaction (PCR):
[0138] Blood samples were allowed to clot at ambient temperature and then were processed within 36 hours by centrifugation to permit separation of the serum from the clotted blood cells. Aliquots of serum were transferred to three sterile storage tubes. Tubes were labeled and stored at ≦-20° C. until delivered by the study monitor to the testing laboratory. Delivery of a few of the samples to the processing laboratory was delayed approximately 12 hours beyond the 24 hours recommended by the study protocol. This is a deviation to the protocol. This delay did not affect the integrity of the serum samples and did not affect the outcome of the study. Serum neutralization titers for IBR, BVDV Type 1 (challenge virus, Singer) and Type 2 (Challenge virus, NVSL 125c) were determined on all sera at the Animal Health Laboratory, Guelph using a constant virus decreasing serum assay in appropriate cell cultures using <500 Tissue Culture Infective Dose50 (TCID50) challenge virus. The starting dilution was 1:4.
[0139] An RT PCR assay for BVD viruses was conducted on pre-colostral serum samples by the Animal Health Laboratory, University of Guelph, Guelph, Ontario. The RT PCR was conducted according to a published procedure. The serum from each calf was tested for gamma-glutamyl transpeptidase (GGT) to help distinguish a calf that had suckled from one that had not. The GGT testing was performed at the Animal Health Laboratory, Ontario Veterinary College, University of Guelph, Guelph, ON using an enzymatic colorimetric method with a Roche/Hitachi 911 Automatic Analyzer.
[0140] As there was only one treatment, the investigator and the laboratory technician who separated the serum from blood samples were not blinded to treatment group assignments. The individuals performing the laboratory examinations of post mortem samples and serum samples were unaware of treatment assignments.
[0141] d. Vaccine and Placebo Control Articles:
[0142] Vaccine and Placebo Control articles used in the trial at the Nebraska trial sites are shown below in Table G. The same serial of test vaccine was used for the pre-breeding vaccination and the trimester enrollment vaccinations.
TABLE-US-00006 TABLE G Serial Test Vaccine Number(s) Use Infectious Bovine Rhinotracheitis-Bovine MK-270A- Pre-breeding Viral Diarrhea-Parainfluenza 3-Respiratory 088 or and trimester Syncytial Vaccine, Modified Live Virus, MK-270B- vaccinations Leptospira Canicola-Grippotyphosa- 088 Hardjo-Icterohaemorrhagiae-Pomona Bacterin, APHIS Product Code 4469.23 Leptospira Canicola-Grippotyphosa- 184-087; Trimester Hardjo-Icterohaemorrhagiae-Pomona 184-089; placebo Bacterin, APHIS Product Code 2665.00 184-090; control (refer to Protocol Deviation 2, vaccinations Addendum 3)
Vaccine and Placebo Control articles used in the trial at the Alberta trial sites are shown below in Table H.
TABLE-US-00007 TABLE H Serial Test Vaccine Number(s) Use Infectious Bovine Rhinotracheitis-Bovine 263-318A Trimester Viral Diarrhea-Parainfluenza 3-Respiratory vaccinations Syncytial Vaccine, Modified Live Virus, Leptospira Canicola-Grippotyphosa- Hardjo-Icterohaemorrhagiae-Pomona Bacterin, APHIS Product Code 1181.24 Sterile Adjuvanted Diluent 807-136 Vaccine Rehydration
[0143] e. Amendments, Deviations and Notes to File:
[0144] There was a single Amendment to the Study Protocol from the Nebraska site. The Amendment is outlined below in Table I.
TABLE-US-00008 TABLE I Amendment Sites # Affected Description Effect on Outcome 1 A&K Describes the decision No effect on the Ranch to use artificial outcome of the insemination for study the A&K ranch
[0145] There were a total of 14 Deviations to the Study Protocol from the Nebraska herds and 3 from the Alberta herd. The Deviations are outlined in the table below in Table J.
TABLE-US-00009 TABLE J Deviation Herds Effect on # Affected Description Outcome Protocol Deviations 1 A&K first The last two cows for the day were assigned to No negative trimester treatment group based upon coin toss effect 2 All three The decision was made to use Lepto 5 bacterin as No negative Nebraska placebo based on a request by the herd owners effect herds 3 All three The decision was made to obtain baseline blood No negative Nebraska samples at the time of trimester vaccination effect herds 4 Raymond and Minimum gestation accepted for enrollment set to No negative A&K first 45 days estimate based upon ultrasound estimates effect trimester by the Site Investigator (45 days equal approximately 40-50 days) 5 A&K first Range between pregnancy check and enrollment No negative trimester was at 20 days, not the 7 days as stated in the effect protocol 6 First trimester The protocol stated that a single herd would No negative enrollment represent one trimester. A portion of the A&K effect herd was enrolled as 1st trimester, with the remainder of the herd enrolled as 2nd trimester. 7 A&K second Randomizations needed to be adjusted due to No negative trimester enrollment of non-qualified cow as well as to effect enrollment balance the outcome of the total number of cows enrolled as Group A and Group B 8 A&K second Adjustment of the enrollment of animals No negative trimester determined to be at 45 days gestation (40-50 days) effect enrollment at the time of initial pregnancy check 9 Williams 3rd Calves from cows and heifers enrolled in the third No negative trimester trimester were vaccinated with clostridial vaccine effect enrollment to prevent scours 10 All Nebraska First and second blood samples were not obtained No negative herds/all three within the two week time period for a number of effect trimesters the animals that had or were found to be open 11 All Nebraska First and second blood samples were not obtained No negative herds/all three within the two week time period for a number of effect trimesters the animals that had calf loss or were found to be open 12 A&K second The calf from cow #86 died due to dystocia. A No negative trimester blood sample was obtained at calving but was effect inadvertently listed and shipped with the blood samples from the Williams herd vaccinations. Cow #86 was enrolled in Group B, placebo. This sample was not tested. A second sample was not obtained. 13 Raymond Calf 940Y was not submitted for necropsy after Included in first trimester death at approximately 48 hours after birth. Cow fetal losses for was enrolled in Treatment Group A 2nd trimester, Group A 14 Williams Calf 5131 died approximately 2 hours after birth. Included in third trimester The calf was ear notched but was not submitted for fetal losses for necropsy. Heifer 5131 was enrolled in Treatment 3rd trimester, Group A Group A Protocol Deviations Affecting the Alberta Site 1 Ashley Herd, The record forms provided in the appendix of the No negative Alberta study protocol were not used. The investigator effect instead kept written records of the study in a calving record book and a calendar daily record. 2 Ashley Herd, All cows in the 3rd trimester group were No negative Alberta vaccinated with Ecostar 2RC (Novartis Animal effect Health) at the time of trimester enrollment vaccination. 3 Ashley Herd, Some blood samples were held for 36 hours prior No negative Alberta to processing effect
[0146] There was a total of 18 Notes to File that were written for the purpose of clarification of parts of the study for the Nebraska sites and 3 Notes to File for the Alberta site, as shown in the table below in Table K.
TABLE-US-00010 TABLE K Note to File Herds Effect on Subject Day Affected Description Outcome Notes to File, Nebraska Trial Sites Change of Ear 148 Raymond Replacement of ear tags, list of No negative Tag Numbers first old and new tags for reference effect trimester enrollment Change of Ear 192 A&K second Replacement of ear tags, list of No negative Tag Numbers trimester old and new tags for reference effect heifers Change of Ear 192 Williams Replacement of ear tags, list of No negative Tag Numbers third old and new tags for reference effect trimester heifers Change of Ear 204 Williams Replacement of ear tags, list of No negative Tag Numbers third old and new tags for reference effect trimester Fetal Shipments 232 Williams Shipment of samples from three No negative third fetuses over a weekend effect trimester Duplicate Ear Tag 279 A&K second A few mature cows and heifers No negative Numbers for trimester were inadvertently given the effect Heifers and Cows same ear tag numbers. The tags of mature cows were changed to have the letter M added Change of Ear 289 Raymond At the time of trimester No negative Tag Numbers first enrollment vaccination ear tags effect trimester were changed for 9 cows. The list provided gives a cross reference for pre-breeding vaccination Assignment to 294 A&K first The A&K ranch cows were No negative groups for and second divided into 3 groups A, B, C effect artificial trimester during breeding process. insemination enrollment Administration of 294 All three This note describes the No negative colostrum to non- Nebraska administration of colostrum to effect; caused suckling calves herds weak calves to provide the initial positive results feeding on necropsy serology Administration of 307 Raymond Cows were poured with No negative non-approved first Permectrin CDS Pour-on for effect product for trimester parasite control parasite control ID discrepancies 344 All three Animal identifications were No negative on SDSU herds incorrect on diagnostic laboratory effect laboratory results results. This list provides a cross reference Removal of cow 365 Williams Cow 3028 aborted during chute No negative 3028 prior to third work on Day 197 prior to effect. enrollment trimester enrollment. The fetal samples vaccination were submitted for testing, the results are included in the raw data. Cow was not enrolled Cow 713 365 A&K second Cow number 713 was not No negative pregnancy checks trimester ultrasounded as scheduled but effect was pregnancy checked and confirmed to be pregnant at enrollment vaccination on Day 458 and was enrolled in Treatment Group A Ear notch not 365 A&K second At necropsy, an ear notch was not No negative collected trimester collected from calf 504Y at the effect time of death Study record 379 A&K first The 82 cows enrolled in the first No negative designation for trimester trimester were included in the effect A&K first enrollment data capture forms for the A&K trimester ranch. First trimester cows that enrollment were enrolled were designated with a red dot in the study files Cross-fostered 379 All Nebraska Reference list for calves that No negative calves herds were cross-fostered effect Removal of heifer 379 A&K second Heifer 577 aborted prior to The results 577 prior to trimester enrollment vaccination. The fetus indicated possible enrollment was sampled and tested. The IBR exposure. results are included in the raw Results could not data. Not enrolled in the trial. be confirmed; not enrolled in the trial Randomization of 428 Raymond The Raymond herd was housed No negative Raymond cows, cows, first in two separate groups with effect first trimester trimester approximately equal numbers in each group. A coin toss was used for group assignment Notes to File, Alberta Trial Site Clarification of 394 Alberta 2nd trimester enrollment Cow 190 No negative death loss, Cow Ashley herd (dam of calf 25Y) died of an effect 190 esophageal abscess. Her calf was cross-fostered to cow 216. A serum sample was not taken from this calf Clarification of 392 Alberta 2nd trimester enrollment Cow 208 No negative death loss, Calf Ashley herd gave birth to calf 28Y. This calf effect 28Y was humanely destroyed after its jaw was fractured. A serum sample had been collected from 28Y. Calf 51Y, a co-twin born to Cow 45, was cross-fostered onto cow 208. Calf 51Y was not bled. Clarification of 397 Alberta a 2nd trimester cow calved on No negative notation on "Here Ashley herd Day 397. Her identification is effect BWF" noted as "Here BWF" and her identification calf was identified as 66Y. This cow had lost her plastic ear tag but had been amongst the group confirmed pregnant and vaccinated for the 2nd trimester. Calf 66Y was bled.
7. Results
[0147] a. Nebraska Sites:
[0148] Ear Notch:
[0149] Ear notch results were all negative for both the enrollment testing of calves and heifers and for testing conducted on dead fetuses and calves. The negative results indicate that none of the enrolled cattle were persistently infected and that none of the fetal and calf losses in the trial were due to persistent infection with BVD.
[0150] Calving Outcome:
[0151] All cows and heifers were followed through calving and the calving outcome recorded for each case. Calving outcome was recorded as either Open (heifer or cow diagnosed as not pregnant, with no calf), Dead (calving resulted in a dead calf not diagnosed as dystocia), or Live (calving resulted in a live calf diagnosed as normal at calving). Calves that died at or immediately after calving due to calving difficulties (dystocia), weather related deaths (frozen in blizzard) or other non-study related causes (calf crushed when stepped on by dam) were removed from the trial. The animals that were removed were not included in the final study results. The Open and Dead cases were combined and included under the category Fetal Losses.
[0152] There were no calving losses/abortions that were diagnosed as due to either IBR or BVD. The total number of cows and heifers and a summary of the results that include all possible study related fetal losses from the first trimester are shown in the following tables.
TABLE-US-00011 TABLE L Summary of the first trimester calving outcome results Treatment Group Total Calf Losses/Total Enrolled Percent Fetal Losses A 7/306 2.3 B 6/274 2.2 Total 13/580 2.2
TABLE-US-00012 TABLE M Summary of the second trimester calving outcome results Treatment Group Total Calf Losses/Total Enrolled Percent Fetal Losses A 1/237 0.4 B 3/235 1.3 Total 4/472 0.8
TABLE-US-00013 TABLE N Summary of the third trimester calving outcome results Treatment Group Total Calf Losses/Total Enrolled Percent Fetal Losses A 5/267 1.9 B 6/267 2.2 Total 11/534 2.1
[0153] Postpartum Observations:
[0154] Calves were observed for 4 weeks postpartum. All calf losses and treatments were recorded. Calves that were lost close to calving were included as a fetal loss and not as a post-calving loss. The results of post-calving observations for all three trimesters showed that the calf losses were low. The treatments consisted primarily of treatments for minor cases of scouring that cleared within 24 to 48 hours.
[0155] A summary of the post-calving treatments and post-calving losses for the first trimester are shown in the tables below.
TABLE-US-00014 TABLE O Summary of the first trimester postpartum treatments Postpartum Treatments/ Treatment Group Total Enrolled Percent Calf Treatments A 6/299 2.0 B 1/268 0.4 Total 7/567 1.2
TABLE-US-00015 TABLE P Summary of the first trimester postpartum calf deaths Postpartum Deaths/ Treatment Group Total Enrolled Percent Calf Deaths A 3/299 1 B 0/268 0.0 Total 3/567 0.5
[0156] A summary of the post-calving treatments and post-calving losses for the second trimester are shown in the following tables.
TABLE-US-00016 TABLE Q Summary of the second trimester postpartum treatments Postpartum Treatments/ Treatment Group Total Enrolled Percent Calf Treatments A 6/236 2.5 B 2/232 0.9 Total 8/468 1.7
TABLE-US-00017 TABLE R Summary of the second trimester postpartum calf deaths Postpartum Deaths/ Treatment Group Total Enrolled Percent Calf Deaths A 0/236 0.0 B 1/232 0.4 Total 1/468 0.2
[0157] A summary of the post-calving treatments and post-calving losses for the third trimester are shown in the following tables.
TABLE-US-00018 TABLE S Summary of the third trimester postpartum treatments Postpartum Treatments/ Treatment Group Total Enrolled Percent Calf Treatments A 10/262 3.8 B 7/261 2.7 Total 17/523 3.3
TABLE-US-00019 TABLE T Summary of the third trimester postpartum calf deaths Postpartum Deaths/ Treatment Group Total Enrolled Percent Calf Deaths A 3/262 1.1 B 1/261 0.4 Total 4/523 0.8
[0158] Laboratory Results:
[0159] Tissue Samples for Detection of IBR, BVD 1 and BVD 2:
[0160] With a few minor exceptions, a full necropsy with tissue sampling was performed on all available fetal and calf losses that occurred during the trial, including dystocia and hypothermia cases.
[0161] A necropsy was not performed and samples for testing were not obtained on calves 940Y or 5131 due to failure of the rancher to report the dead calf to the site investigator for necropsy. An ear notch sample was taken from calf 5131 and was reported as negative. Calf 940Y was from a cow enrolled in Group A of the Raymond first trimester herd. Calf 940Y died approximately 48 hours after birth. Calf 5131 was from a heifer enrolled in Group A of the Williams third trimester herd. Calf 5131 died approximately 2 hours after birth.
[0162] Animals that died due to a cause obviously unrelated to the study, for example euthanized due to broken leg, were not submitted for necropsy. Tissues and body fluid samples, as available, were submitted to a laboratory for analysis. Tests specific for detection of IBR and BVD were performed by the laboratory. In addition, RTI performed virus isolations on all submitted tissues.
[0163] All tests for IBR and BVD 1 and BVD 2 viral detection and isolation on all fetal and calf tissues were negative.
[0164] Heart blood and other body fluids, as available at necropsy, were tested for antibody to IBR, BVD 1 and BVD 2 by the laboratory. There was a total of six fetuses or calves that tested positive for antibody to IBR, BVD 1 and/or BVD 2. These are summarized in Table U.
TABLE-US-00020 TABLE U Fetuses and calves with reported positive antibody results from necropsy fluid samples Treatment IBR SN BVD 1 SN BVD 2 SN Fetus/Calf # Herd/Trimester Group Diagnosis Titer Titer Titer 577 A&K 2nd/Not Not Aspergillus sp. 1:8 (heart <1:8 <1:8 enrolled Applicable abortion blood) 207Y Raymond/1st A Weak calf, died at <1:4 1:64 (pleural 1:128 24 hours (fed fluid) (pleural colostrum) 1:32(heart fluid) blood) 1:64(heart blood) 86 A&K/2nd B Died, dystocia <1:4 1:16 (heart 1:32 (heart blood) blood) 5128 Williams/3rd A Died, dystocia <1:4 <1:8 1:16 (pleural fluid) 5013 Williams/3rd A Enteritis, had 1:8 1:128 1:512 suckled (pleural (pleural (pleural fluid) fluid) fluid) 5020 Williams/3rd B Euthanized after 1:4 1:64 (pleural 1:32 (pleural birth (pleural fluid) fluid) malformed had fluid) suckled
[0165] Since the results on the pleural fluids on the BVD 1 and BVD 2 serum neutralizations for #86 and #5128 were borderline (one to two 2-fold dilutions above negative, with #86, one dilution above negative for only one BVD type), retests were requested to confirm the results. In both cases, attempts at retests were not successful due to the level of toxicity and/or contamination in the sample.
[0166] Serum Samples from Cows and Heifers Having Fetal Loss:
[0167] Serum samples were obtained from cows and heifers at the time of diagnosis of calf loss or status as open and again at approximately two weeks after the diagnosis. These serum samples as well as the serum sample from the animal that was obtained at enrollment vaccination were tested for the level of serum neutralizing antibody to IBR, BVD 1 and BVD 2. The cow/heifers tested are summarized in Table V below.
TABLE-US-00021 TABLE V Serum neutralization results from heifers and cows with calf loss Treatment Animal # Herd/Trimester Group Reason for Sampling 522Y Raymond/First B Stillborn calf 4108 A&K/First A Open 210 A&K/Second B Open 018 A&K/Second B Dead Calf (dystocia) 391 A&K/First B Dead Calf (dystocia) 527 A&K/Second B Dead Calf 593 A&K/Second B Dead Calf, pre-mature 433 A&K/First B Open 220Y Raymond/First A Open 218Y Raymond/First A Dead Calf (dystocia) 243 O Raymond/First B Open 10 O Raymond/First B Open 166Y Raymond/First A Open 300W Raymond/First B Open 516Y Raymond/First B Open 925 A&K/Second A Dead Calf (dystocia) 859 A&K/Second B Open 630 A&K/Second A Open 950Y Raymond/First A Stillborn Calf 426Y Raymond/First A Dead Calf (dystocia) 813Y Raymond/First A Open 945Y Raymond/First A Open 620Y Raymond/First A Open 5127 Williams/Third B Dead Calf (dystocia) 5045 Williams/Third A Dead Calf (dystocia) 5075 Williams/Third B Dead Calf (dystocia) 5109 Williams/Third A Dead Calf (dystocia) 024 Williams/Third B Stillborn Calf 125 Williams/Third B Open 4032 Williams/Third B Open 4040 Williams/Third A Open 341 Williams/Third B Calf died after birth - infected navel 5131 Williams/Third A Dead Calf - Premature 5128 Williams/Third A Dead Calf (dystocia) 947 A&K/Second B Live Calf; died with/in 48 hours 1045 Williams/Third A Live Calf, died bacterial enteritis 2056 Williams/Third B Open 4010 Williams/Third A Stillborn Calf 5012 Williams/Third B Calf died, dystocia 5020 Williams/Third B Euthanized, malformed 5030 Williams/Third B Dead Calf (dystocia) 5086 Williams/Third A Died, stepped on by cow 5103 Williams/Third A Open 577 A&K/Not enrolled Not Aborted Applicable 5041 Williams/Third A Twins, premature 5002 Williams/Third B Euthanized, navel hernia
[0168] The serological results for IBR, BVD 1 and BVD 2 were all within the levels that would be expected in a well vaccinated herd. There were a number of cows and heifers that showed a significant rise in titer after vaccination, but none of the animals showed a significant rise between the time of sampling at calf loss and the post-calving blood sampling, which would be indicative of a calf loss due to either IBR or BVD.
[0169] b. Statistical Analysis:
[0170] Based upon the guidelines published in VS Memorandum 800.110, for each group, the calving rate, calf losses due to unknown causes, and the health status of the calves up to 4 weeks post partum were determined and summarized. The Clopper-Pearson 95% confidence interval for the aborting fractions due to IBR and BVD was calculated for each trimester group. All rate estimates and confidence intervals were calculated for each treatment group and for the groups combined. PROC FREQ of the SAS® System, version 9.1.3, was used to calculate the proportions. The rates (%) were obtained by multiplying the proportions by 100. The Clopper-Pearson confidence intervals were calculated using StatXact from Cytel Studio 7.
[0171] Abortion Rate Due to IBRV/BVDV:
[0172] For all three trimesters, no cows or heifers (0.0%) in either group were diagnosed as having aborted due to IBRV/BVDV. For the first trimester, the upper 95% confidence limits were 1.2%, 1.3%, and 0.6% respectively for group A, group B, and the groups combined. For the second trimester, the upper 95% confidence limits were 1.5%, 1.6%, and 0.8% respectively for group A, group B, and the groups combined. For the third trimester, the upper 95% confidence limits were 1.4%, 1.4%, and 0.7% respectively for group A, group B, and the groups combined.
[0173] Abortion Rate Due to Any Cause:
[0174] For all three trimesters, the estimated abortion rate due to any cause was less than 5% for both groups and for the groups combined. For the first trimester, the estimated rate was 2.3% for group A, 2.2% for group B, and 2.2% for the combined groups. For the second trimester, the rate was 0.4% for group A, 1.3% for group B, and 0.8% for the combined groups. For the third trimester, the rate was 1.9% for group A, 2.2% for group B, and 2.1% for the combined groups.
[0175] Post-Calving Treatment Rate:
[0176] The estimated rate of treatment for any cause for both treatment groups and groups combined was ≦3.8% for all three trimester groups. For the first trimester, the estimated rate was 2.0% for group A, 0.4% for group B, and 1.2% for the groups combined. For the second trimester, the estimated rate was 2.5% for group A, 0.9% for group B, and 1.7% for the groups combined. For the third trimester, the estimated rate was 3.8% for group A, 2.7% for group B, and 3.3% for the groups combined.
[0177] Post-Calving Death Rate:
[0178] The estimated rate of death by any cause for both treatment groups and groups combined was ≦1.1% for all three trimester groups. For the first trimester, the estimated rate was 1.0% for group A, 0.0% for group B, and 0.5% for the groups combined. For the second trimester, the estimated rate was 0.0% for group A, 0.4% for group B, and 0.2% for the groups combined. For the third trimester, the estimated rate was 1.1% for group A, 0.4% for group B, and 0.8% for the groups combined.
[0179] c. Alberta Site Results:
[0180] Calving Outcome:
[0181] In group one (third trimester), one cow (#119) gave birth to twins. One co-twin was dead at delivery and the second died shortly after birth. Both calves were subjected to a post mortem examination, and had no gross or histopathological or virological evidence of exposure to IBR or BVD viruses. In summary, for group 1, 120 cows were vaccinated with one pregnancy loss. This gives a 0.8% pregnancy loss for group 1, third trimester.
[0182] In group two (second trimester), cow 137 died of peritonitis as a sequel to surgical repair of a vaginal prolapse before she had an opportunity to give birth. Cow 115 was observed to abort a fetus, but the fetus had been consumed by wildlife so it was not available for post mortem examination. Three cows (#264, #132, #109) gave birth to calves that were either dead at birth or died shortly thereafter and were classified as stillbirths. All were subjected to a post mortem examination and had no gross or histopathological or virological evidence of exposure to IBR or BVD viruses (see attached post mortem reports Addendum 3). One cow (#216) aborted a fetus that was recovered. It was negative for exposure to IBR or BVD viruses on gross, histopathological and virological examination (see attached post mortem reports Addendum 3). Cow 161 had not calved and was determined to be not pregnant by rectal palpation. The loss of the fetus had not been observed and so it was not possible to conduct a post mortem examination.
[0183] In summary, among the 140 enrolled cows that finished the trial in group two, 6 cows either lost a fetus during gestation or gave birth to a stillborn calf. Four of these fetuses and calves were recovered and subjected to a post mortem examination. In each case, the post mortem examination showed no evidence of in utero exposure to IBRV, BVD1 or BVD2. For the remaining two cows, no fetus was available for post mortem examination. This gives a 4.3% pregnancy loss for the second trimester group of cows.
[0184] Calf Treatments in First 45 Days of Life:
[0185] No calves born in the first or second calving season were treated for illness in their first 45 days of life.
[0186] Results on Calves that had Suckled Colostrum:
[0187] In group one, the investigator indicated that 5 of the 65 calves had been suspected to have suckled colostrum before a blood sample was collected (calves: 8Y, 16Y, 23R, 25Y, 46R). According to the GGT results, 4 calves (8R, 8Y, 25Y, 46R) had nursed (GGT>51 U/L) and each of these calves were seropositive for IBR, BVD1 and BVD2. These calves were seropositive as a result of having absorbed colostral antibody. Of the four calves that had laboratory tests indicating suckling, three had been identified by the investigator as having nursed. Calves 16Y and 23R, which were suspected to have suckled, were seronegative for IBR, BVD1 and BVD2 and negative for BVDV on RT-PCR and IBRV on virus isolation. If calves 16Y and 23R did nurse, then nursing must have occurred immediately prior to the blood being drawn, with the time interval insufficient for antibody and GGT transfer and elevation. The negative antibody and virus test results indicate that these calves were not exposed to IBR, BVD1 or BVD2. In group two (second trimester), the investigator indicated that 3 of the 67 calves had been suspected to have suckled colostrum before a blood sample was collected (53R, 61R, 72R). Calves 53R and 72R were seronegative to IBR, BVD1 and BVD2 and negative for BVDV on RT-PCR and IBRV on virus isolation. If calves 53R and 72R did nurse, then nursing must have occurred immediately prior to the blood being drawn, with the time interval insufficient for antibody transfer and GGT elevation. The negative antibody and virus isolation results indicate that these calves were not exposed to IBR, BVD1 or BVD2. The investigator indicated that calf 61R was suspected to have suckled. Although the GGT results were below the upper limit of the normal range (51 U/L), the antibody testing indicated that the calf had low virus neutralizing activity against IBR (1:4), BVD1 (1:48) and BVD2 (1:6). Based on the investigator's observations and the test results having low positive antibody for all three viruses, suckling must have occurred very close to when the serum sample for 61R was obtained. Results of IBR virus isolation and BVD 1 and BVD 2 RT PCR testing on the serum from calf 61R were negative. Calf 37R was determined to have nursed unobserved because its GGT value was 2143 U/L (upper limit of normal range: 51 U/L). It was seropositive for IBR, BVD1 and BVD and negative for BVDV on RT-PCR and IBRV on virus isolation.
TABLE-US-00022 TABLE W Summary of laboratory results of calves testing seropositive: GGT IBR BVD1 BVD2 BVDV RT- IBRV Calf ID U/L VN VN VN PCR Virus Isolation First Calving Season 8R 1456 1:384 1:2048 1:256 Neg Neg 8Y 746 1:24 1:1024 1:256 Neg Neg 25Y 595 1:16 1:512 1:96 Neg Neg 46R 200 1:4 1:64 1:16 Neg Neg Second Calving Season 61R 26 1:4 1:64 1:6 Neg Neg 37R 2143 >256 >4096 >4096 Neg Neg
[0188] Results on Enrolled Calves:
[0189] In group two, second trimester, two calves that were otherwise healthy, died by misadventure in the first 30 days of life. Calf 28Y was injured, likely from a cow's kick, causing a broken jaw. It was humanely destroyed and did not have a post mortem examination. Calf 28Y had been identified for blood collection at birth. At birth, calf 28Y was seronegative for IBR, BVD1 and BVD2 and negative for BVDV on RT-PCR and IBRV on virus isolation. Calf #56R was swept down an embankment during a severe rain storm and was not available for post mortem examination. Calf 56R had been identified for blood collection at birth. At birth, calf 56R was seronegative for IBR, BVD1 and BVD2 and negative for BVDV on RT-PCR and IBRV on virus isolation.
[0190] In group two, the serum samples from two calves (49R, 98Y) were lost when, on two separate occasions, the centrifuge at the Fort Macleod Veterinary Clinic malfunctioned. The malfunction caused the clotted blood tube to break with complete loss of the serum sample. A total of 65 calves from cows in the third trimester (group 1) were bled shortly after calving. Based upon a combination of investigator observations, antibody testing for IBR and BVD 1 and BVD 2 and GGT testing, the results indicated that four of the calves may have suckled prior to sampling (8R, 8Y, 25Y, 46R). An additional two calves (16Y, 23R) were suspected of having suckled but were seronegative and had normal GGT results. Due to the question on the validity of the pre-colostral serum sampling, all six calves were removed from further consideration in the study. The remaining 59 calves from the third trimester group 1 were all negative for antibody to IBR, BVD 1 and BVD 2. All IBR virus isolations and BVD 1 and BVD 2 RT PCR test results from serum were negative for all calves. There were no post-calving losses due to health problems in this group. A total of 67 calves from cows in the second trimester (group 2) were bled shortly after calving. Based upon a combination of investigator observations, antibody testing for IBR and BVD 1 and BVD 2 and GGT testing, results indicated that two of the calves (37R, 61R) may have suckled prior to sampling. The investigator indicated there was evidence that an additional two calves (53R, 72R) may had suckled. Results of testing from these two calves were negative for both antibody and GGT, indicating that if suckling had occurred, the colostrum was consumed close enough to the blood sampling that passive transfer had not yet occurred. Due to the question of validity of the pre-colostral serum sampling, all four calves were removed from further consideration in the study. Two serum samples were lost due to malfunctions during the processing of the serum; therefore these two calves were also removed from further consideration in the study. The remaining 61 calves from the second trimester group 2 were all negative for antibody to IBR, BVD 1 and BVD 2. The blood samples from all calves were negative for IBR virus isolation and BVD 1 and BVD 2 testing by RT PCR. There were no post calving losses in this group due to health problems.
[0191] d. Discussion:
[0192] This study was completed in four working cow/calf herds, three located near Ainsworth, Nebraska and a fourth located in Alberta, Canada. Cows and heifers enrolled in the study were vaccinated prior to breeding and at the time of enrollment in the trial with vaccine containing field dose levels of cytopathic modified live IBR and BVD Type 1 and BVD Type 2 components (Boehringer Ingelheim).
[0193] For the non-serological Nebraska portion of the trial, data from a total of 580 cattle, 306 vaccinates and 274 placebo controls, were obtained for the first trimester. Data from a total of 472 cattle, 237 vaccinates and 235 placebo controls, were obtained for the second trimester. Data from a total of 534 cattle, 267 vaccinates and 267 controls were obtained for the third trimester.
[0194] All enrolled cattle were followed through calving and the calving outcome recorded. Any fetuses or calves recovered from enrolled cattle were subjected to full necropsy that included tests specific to detect IBR and BVD viral agents, both by histological techniques and by virus isolation. There were no positive results in any of the tests that would indicate IBR or BVD was involved in any of the calf losses.
[0195] Dystocia, the major cause of new born calf loss, is defined as a difficult or obstructive calving process. For the purposes of this trial, a diagnosis of dystocia as responsible for calf loss was made based upon observations made by the producer and/or Site Veterinarian. The observations were recorded either during calving or at the time of necropsy. Per the agreement made with the Center for Veterinary Biologics prior to the start of the study, calving losses diagnosed as due to dystocia were not included in the overall undiagnosed pregnancy loss rate for the enrolled cattle. After removal of calving losses due to dystocia, the overall undiagnosed calf losses for the cattle enrolled in the trial were below the 5% rate recommended in the guideline. The highest levels were seen in the first trimester group, with 2.3% and 2.2% for the vaccinates and placebo controls respectively. This is to be expected as the enrollment/trimester pregnancy check and vaccination for these cows and heifers was conducted in the first trimester. For the second and third trimester groups, the pregnancy check conducted at the time of enrollment presented the opportunity to eliminate any pregnancy losses that had occurred during the earlier parts of gestation. The level of pregnancy losses in all three trimesters are extremely low and prove the safety of the vaccination of these animals with the modified live vaccine component.
[0196] Heart blood and other body fluids, as available at necropsy, were tested for antibody to IBR, BVD 1 and BVD 2 by the laboratory. There were a total of six fetuses that tested positive for antibody, however, due to either site practices (forced feeding of colostrum) or testing problems due to sample toxicity/contamination and the inability to confirm the initial results, these results do not impact the outcome of the study.
[0197] Fetus from heifer 577 was reported to have a low levels of antibody to IBR in heart blood. This result was not confirmed. The heifer from the A&K herd aborted prior to the second (gestational) vaccination and was therefore not qualified for enrollment in the trial.
[0198] Three calves (207Y Group A 1st trimester; 5013 Group A 3rd trimester and 5020 Group B 3rd trimester) died within approximately 48 hours of birth. Fluids from each of these calves showed relatively high antibody titers to IBR, BVD 1 and BVD 2. However, all three calves had either suckled or were force-fed (tubed) with colostrum prior to death, explaining the positive antibody results.
[0199] Fetus from cow 86, Group B, second trimester, died after birth by cesarean section. Death was due to dystocia. The calf presented with hydroperitoneum. Heart blood samples obtained at necropsy were reported as having low titers to BVD 1 and BVD 2. The diagnostic laboratory reported that this sample was found to be toxic to the cell cultures, and therefore the initial results could not be confirmed. The reported problems with toxicity of the serum sample and the inability to confirm the test results indicate that the original results should be considered suspect and, therefore do not impact the outcome of the study.
[0200] Fetus from heifer 5128, Group A, third trimester, died at birth due to dystocia. Testing for antibody on pleural fluid initially was reported as having a low titer to BVD 2, and negative for antibody to BVD Type 1. The diagnostic laboratory reported that this sample was found to be toxic to the cell cultures, and therefore the initial results could not be confirmed. The reported low antibody titer and the problems with toxicity of the pleural fluid sample and the inability to confirm the test results indicate that these results should be considered to be suspect and, therefore do not impact the outcome of the study.
[0201] In addition, blood samples were taken at the time that the enrollment vaccination (trimester vaccination) was administered. Paired blood samples were also obtained from cows and heifers at the time of diagnosis of pregnancy loss and at an interval of approximately two weeks after diagnosis. Those cattle diagnosed as open, with no recovery of fetal tissue, were of particular interest. The three samples (enrollment vaccination as well as paired samples) were tested to determine the level of antibody to IBR and BVD 1 and BVD 2 at the time of vaccination, at the time of diagnosis of pregnancy loss and at the interval post calf loss.
[0202] The serological results for IBR, BVD 1 and BVD 2 in these cattle were as expected for a well vaccinated herd. There were a number of cows and heifers that showed a significant rise in titer after vaccination, but none of the animals showed a significant rise between the time of sampling at the diagnosis of calf loss and the post-calving blood sampling, which would be indicative of a calf loss due to either IBR or BVD.
[0203] All calves at the Nebraska sites were followed for 4 weeks post partum. Rates of post partum illness, treatments and deaths in the enrolled calves in all three herds were very low. All three herds experienced minor illnesses that required treatment, most of which were episodes of scouring that persisted for 24 to 48 hours. The highest treatment rates were noted in the Williams herd (third trimester), in which the treatment rate was 3.8% in the vaccinates and 2.7% in the placebo controls. These treatment rates are low for working cow/calf herds.
[0204] The post-calving death rates in all three herds were very low and not above the rates that would be expected in normal working cow/calf herds. Necropsy results from all calf deaths were negative for virus pathogens in the post calving deaths.
[0205] At the Alberta site, the IBR, BVD 1 and BVD 2 serum neutralizing antibody status in pre-colostral serum samples was determined in a total of 61 calves from the second trimester and 59 calves from the third trimester. Six calves were removed from consideration in both the second and the third trimester due to either equipment malfunction or concerns on the validity of the pre-colostral sample status. The concerns over the validity of the samples were documented by the investigator in the study records. All serum samples from those calves having valid pre-colostral samples were negative for neutralizing antibody to IBR, BVD 1 and BVD 2.
8. CONCLUSION
[0206] The results of this study show no indication that vaccination of previously vaccinated pregnant cattle in the first, second or third trimester with the modified live IBR, BVD Type 1 and BVD 2 would result in deleterious effects to either the cow, heifer or the calves.
REFERENCES
[0207] The teachings and contents of all references (articles, patents, book portions, presentations, and the like) cited herein, including those listed below, are expressly incorporated by reference herein.
[0208] Baker, J. C. 1987. Bovine viral diarrhea virus: a review. J. Am. Vet. Med. Assoc. 190: 1449-1458.
[0209] Heinz, F. X., Collett, M. S., Purcell., R. H., Cold, E. A., Howard, C. R., Houghton, M., Moormann, R. J. M., Rice, C. M., and Thiel, H.-J. 2000. Family Flaviviridae. PP 859-878. In: Virus Taxonomy (van Regenmortel, H. H. V., Fauquet, C. M., and Bishop, D. H. L, Eds.). Academic Press, San Diego.
[0210] Lindenbach, B. D., and Rice, C. M. 2001. The pestiviruses. In Fields Virology, eds. Knipe, Moennig, V. and Plagemann, J. 1992. The pestiviruses. Adv. Virus Res. 41: 53-91.
[0211] Thiel, H.-J., Stark, R., Weiland, E., Rumenapf, T. & Meyers, G. 1991. Hog cholera virus: molecular composition of virions from a pestivirus. J. Virol. 65: 4705-4712.31.
Sequence CWU
1
1
5112665DNABovine Viral Diarrhea Virus Type I 1gtatacgagt actttagcta
atctcgtata cagattggac gttgacaaaa tattgaattg 60aaaatgtagg gaatcttccc
ctcagcgaag gccgaaaaga ggctaaccac gcccttagta 120ggactagcaa aaggagggga
ctagcggtag cagtgagttc attggatggc cgaacccctg 180agtacagggg agtcgtcaat
ggttcgacac tccttcagtt gaggagtctc gagatgccat 240gtggacgagg gcatgcccac
ggcacatctt aacccatgcg ggggctgcat gggtgaaagc 300gccattcgtg gcgttatgga
cacagcctga tagggtgtag cagagacctg ctatcccgct 360agtaaaaaaa ctctgctgta
catggcacat ggagttgttt tcaaatgaac ttttatacaa 420aacatataaa caaaaaccag
aaggtgttgt ggaacctgtt tacgacatca acgggtgtcc 480attgtttgga gagagcagcg
acgtacaccc acaatccaca ctaaaactac cacacctacg 540aggcagcggt gacatcctga
ccaatgctag gtccctgccg cgtaaaggtg actgccggaa 600aggcaacgca aatggagcgg
tgagtggtat ctatatcaaa ccaggaccga tttactatca 660ggattatgtg gggcccgtct
atcatagagc cccactggaa ctatgtagag aggcaagcat 720gtgtgaaact actaggagag
ttggcagagt gaccggtagt aacgggaaat tataccacat 780ctatatttgc atagacgggt
gtatcctcct aaagagggcg actaggaacc aaccagaagt 840cctcaaatgg gtatacaaca
gattaaattg cccattgtgg gtcaccagct gctccggtga 900agagagtaag ggtgctacaa
gcaagaagca acctaagcca gataggatag aaaaaggcaa 960gatgaaaata gcccctaaag
agacagaaaa agattgcaaa accagacccc cggatgcaac 1020cgtagtagta gaaggggtta
agtaccaggt gaagaagaag ggaaaagtaa ggggaaaaaa 1080tactcaagac gggttgtatc
acaataagaa taagccccct gaatcaagaa agaaattgga 1140gaaggcactg ctagcgtggg
ccatcttagc agcggttctg cttcagctgg taacgggaga 1200gaacattacc cagtggaact
tgatggacaa cggcaccgaa ggtatacagc aarctatgtt 1260cctgagaggg gtgaacagga
gtctacatgg aatttggccc gagaagattt gcaccggagt 1320accaactcac ttagcaacag
actacgagct caaggagata gtgggaatga tggacgcgag 1380tgagaagacc aactacacat
gttgcaggtt gcaaaggcat gagtggaaca aacatggttg 1440gtgcaattgg tttcatatag
aaccgtggat atggctgatg aacaagaccc aaagcaactt 1500gactgaagga cagccrccta
gggagtgtgc tgtaacttgt aggtatgaca gggaaacaga 1560attgaacatc gtaacacagg
ctagggacag gcctacaact ctgacaggct gcaagaaagg 1620caagaaattt tcctttgcgg
gggttgtact ggatgggccc tgcaacttta aagtatcagt 1680tgaagacgtg ctgttcaagg
aacacgattg tggcaacatg ctacaggaga ccgcgataca 1740gctactcgat ggggcaacca
acaccattga gggagcaagg gcagggacgg ccaagttgac 1800aacctggtta gggaagcaat
tacggaccct tggtaggaag ttggagaata aaagcaaagc 1860atggtttggt gcacacgcag
cgagcccata ctgtgaagtg gagaggaaga tcggctacat 1920ctggtataca aaaaactgca
ctccagcttg cctgccaaga aacactaaga taataggccc 1980cgggaagttc gataccaacg
ccgaagatgg caaaatactc catgagatgg gagggcacct 2040ctcagaattt gccctattgt
ccttggtggt tctgtccgac tttgccccag aaaccgcgag 2100tgtcatctac ttggttctac
atttcgcgat cccgcaaagt cacattaacg tagacacatg 2160cgacaagagc cagctaaatt
taacggtcgc aactacagta gcagaagtca taccagggac 2220agtgtggaac ctaggaaagt
atgtctgcat aagaccagac tggtggccat atgaaacgac 2280cacagtcttt gttttagagg
aagcaggaca agtaattaaa ttggggctaa gggccatcag 2340agacttaacc aggatttgga
atgctgccac cacaacagcc ttcctagtct tccttgtgaa 2400agtactgagg ggacaattaa
tccaagggct attatggctg atgctaataa caggggcaca 2460gggcttccct gaatgcaaag
agggcttcca atatgccata tcaaaagaca aaaaaatagg 2520accactgggg ccagagagtt
taactacaac atggcacctt cctaccaaaa aaatagtgga 2580ctctatggta caggtgtggt
gtgatggaaa agacttgaaa atattaaaaa cgtgcacaaa 2640ggaagagagg tacttagtgg
ctgtgcacga aagagccctg tcaaccagtg ctgagttcat 2700gcagatcagt agtgggacaa
aaggcccaga agtgatagat atgcctgatg actttgaatt 2760tgggctctgc ccttgtgatt
caaaaccggt aataaggggg aagttcaatg ccagcctatt 2820gaacggacca gctttccaga
tggtatgccc acaggggtgg actggtacaa tagaatgcat 2880cctggcgaac caagacacct
tggacacaac tgtcgttagg acatatagaa gaactactcc 2940atttcagcgg agaaaatggt
gtacctatga aaagataata ggggaagata tccatgaatg 3000cattctagga ggaaactgga
catgcataac tggtgatcat agcaagttga aagatgggcc 3060tatcaagaag tgtaagtggt
gcagctacga cttcttcaat tcagaaggac tgccacacta 3120cccaataggt aagtgcatgc
tcatcaatga gagtgggtac aggtatgtag atgacacctc 3180ttgtgatagg ggtggtgtag
ccatagttca aacaggtact gtaaagtgta gaataggcaa 3240caccacggtg caggttatcg
ctactaacac tgacctggga cccatgccct gcagcccagc 3300tgaggtgata gcaagtgaag
gaccagtgga aaagacggcg tgcacgttta actattcaga 3360gacactacct aataagtatt
atgagccaag ggaccagtac ttccaacaat acatgttaaa 3420agggaagtgg caatattggt
ttgacctgga ttctatagac caccacaaag actacttttc 3480agagttcata gtcatagcag
tggtagcctt gctaggtggt aagtatgtac tgtggctctt 3540agtaacatat atgatactgt
ctgagcagat ggctatgggt gctggagtaa gtaccgaaga 3600gatagtcatg ataggcaact
ttttgacaca cagtgacatc gaggttgtgg tctattttct 3660tcttttgtac ttaataatca
aagaggaact ggtgaggaaa tgggttatgc tagtgtacca 3720catccttgta gtaaatccta
tgaaaacaat aggggttayc ctactaatgc tagggggggt 3780ggtgaaggcc agcaaaatca
atactgatga ccagagtgct atggacccat gttttcttct 3840cgtaacaggc ttagtggccg
ttttgatgat cgctagaaga gaacctgcca cctttccgct 3900ggttgcagca ttactagcaa
taagaacatc aggattccta ctacccgcta gcattgatat 3960aactgtagca gtagtgctga
ttgtacttct gctagctagc tacttaacag actacttcag 4020atataaaaag tggcttcaat
tttcatttag tctgatagct ggtatttttg tcataaggag 4080tttgaaacat atcaaccaga
tggaggtacc agaaatatct atgccaagtt ggagacctct 4140agcccttgtt attttctata
taatatctac agctataacc actagttggg acattgactt 4200agcaggcttc ctgctgcaat
gggcgccagc agtgatcatg atggctacca tgtgggcaga 4260ctttttgact ctaatcatag
tcctacccag ttacgagctg tctaagcttt acttcctgaa 4320gaatgtcagg actgatgtag
aaaagaactg gctcggcaag gtgaaataca gacagatcag 4380ctcagtttat gatatctgtg
acagtgaaga agcagtatac ctatttccat caaggcataa 4440gagcgggagc agaccagatt
ttgtattacc ttttttgaaa gccgtgttaa taagctgcat 4500cagtagccaa tggcaggtgg
tctacatttc ctacctaata ctggaaatta catactatat 4560gcacaggaaa atcatagatg
aggtgtcagg aggagcaaat ttcttgtcaa gacttatagc 4620agccatcata gaattaaact
gggccataga tgatgaggaa tgtaaaggac tgaagaaatt 4680atatctctta tcagggagag
taaggaattt gatagttaaa cacaaggtaa gaaatgaagc 4740cgtccacagg tggtttggtg
aggaggaaat atacggggta cccaaggtaa tcaccatcat 4800aaaagctagt accctcagca
aaagtaggca ctgcataatc tgcacaatct gtgaagggaa 4860agattggaat ggagccaact
gcccaaagtg tggaagacaa gggaaaccca taacatgcgg 4920aatgacactc gcagactttg
aggagaaaca ttacaaaaaa atatttataa gagaaggatg 4980ccaagaagca atgaatacga
tgatgtgcag ccgatgccag ggaaagcata ggaggtttga 5040aatggaccgg gaacctaaga
gtgccagata ctgtgctgag tgtaataggc tgcatcctgc 5100tgaggaaggt gacttttggg
cagagtcaag catgttgggc ctcaaaatca cctactttgc 5160gctgatggat ggaaaggtgt
atgatatcac agagtgggct ggatgccagc gtgtgggaat 5220ctccccagat acccacagag
tccctaatca catctcattt ggttcacgga tgccaggcac 5280cagtgggcgg cagagagcta
ctccagatgc ccctcctgct gaccttcagg atttcttgag 5340ccggatcttt caagtacccc
caggccacga cggacctttc agagaagagt ataagggtta 5400tatccaatac gcagccagag
ggcaactctt tctgaggaac ctaccaattc tagcgacgaa 5460gatgaagcta ctaatggtgg
ggaaccttgg cgcggaagtt ggcgacctgg agcacctggg 5520atgggtactg agagggccag
ccgtgtgcaa gaaaattacc aaccatgaga agtgccacgt 5580aaatatcatg gacaaactaa
ctgcattctt tggaattatg cctagaggca caacccctag 5640ggcacccgtg aggttcccca
cagcattact gaaagtgaga agggggctag agacgggatg 5700ggcctacacg catcaaggag
ggatcagctc ggtagaccat gtcacagctg gaaaggattt 5760actagtgtgt gacagtatgg
gtaggaccag ggttgtctgc catagtaaca ataagatgac 5820tgatgagact gagtatggca
tcaagaccga ctctgggtgt cccgaaggtg caaggtgtta 5880cgtgttaaac ccagaagccg
taaacatttc tggcacaaaa ggagctatgg tacatctcca 5940gaaaacaggg ggggagttca
catgcgtcac tgcctcaggg actccggctt tctttgacct 6000gaaaaatcta aaaggttggt
ctgggctacc aatttttgaa gcatccagtg gcagggtggt 6060tggtagggtg aaagtcggca
aaaatgagga ttccaagccc accaaactaa tgagtgggat 6120ccagacggtg tccaagaacc
agacggacct agcagacatt gtaaaaaaat tgaccagtat 6180gaacagagga gagtttaaac
agataacact ggccactggg gcaggaaaaa cgacggagct 6240gccaaggtcc gtcatagagg
agatagggag acacaaaagg gtcttagtcc tgataccatt 6300gagagccgct gcagagtcag
tgtaccaata tatgagagtg aagtacccaa gtatatcttt 6360caatctgaga ataggagata
tgaaagaagg tgacatggcc actggtatca cttatgcctc 6420atatgggtac ttttgccagc
ttcctcagcc caaactgaga gctgccatgg tagagtactc 6480atatatattc ttagatgagt
atcactgcgc tacacctgag caattagcaa taattggtaa 6540gatacacaga tttgctgaaa
atctcagagt ggtagcaatg acagcaaccc cagctggcac 6600ggtcacgacg actggtcaga
aacaccctat agaggagttt atagccccag aggtaatgaa 6660gggtgaagat ctaggaagtg
aatacttgga tattgcaggg ctgaagatac caactgaaga 6720gatgaaaggc aacatgctcg
tttttgtgcc aaccagaaat atggcagtag aaacagctaa 6780gaaattgaag gcaaaagggt
acaactctgg atactattat agtggggaaa acccagaaaa 6840cctgagggtg gtaacatcgc
aatccccgta tgtggtagta gccaccaatg ccatagagtc 6900aggtgtgaca ttaccagact
tagatacagt tgtagacact ggactaaagt gtgagaagag 6960ggtgaggata tcttcaaaaa
tgcccttcat tgtaacagga ctcaagagaa tggcagtcac 7020tataggagag caagcccagc
gcaggggtag agtaggaaga gttaagccag gtaggtacta 7080tagaagtcag gaaacggctt
cagggtcaaa agattaccat tacgacctac tacaggctca 7140gaggtacgga atagaagatg
ggattaatgt aacaaagtca ttcagggaga tgaactatga 7200ttggagcctt tatgaggagg
acagcctgat gataactcag ctcgaggtcc tcaacaacct 7260ccttatatca gaagacctgc
ctgccgcagt gaagaacatc atggctcgga ctgaccaccc 7320agaacccata caactggcct
ataacagtta tgaaaatcaa attccagtgc tattcccaaa 7380gatyaaaaac ggtgaggtga
cagacagtta tgagaattac acatacctca atgcaagaaa 7440actaggagag gacgtaccag
cgtatgtgta cgctacagag gatgaggatc tagcagtgga 7500ccttctaggt atggattggc
cggacccagg caatcagcag gtggtagaga cagggagggc 7560attaaaacaa gtaactggct
tatctacagc agagaatgcc ctcttgatag ccctattcgg 7620ctacgtcggg taccagacac
tttcaaaaag gcatatacca atgatcactg acatctatac 7680gcttgaagac cataggctgg
aggacacaac ccacctccag tttgccccga atgctataag 7740gactgacggc aaggactcag
agttgaagga attagctgtc ggagaccttg ataaatatgt 7800ggatgcactg gtggactact
ccaaacaagg gatgaagttt atcaaagtcc aagctgaaaa 7860ggtcaaggac tcccattcca
caaaggaagg cttgcaaaca atcaaggagt atgtggataa 7920gttcatacaa tcactaatag
agaacaagga ggagatcatc aggtatggac tatggggagc 7980tcacacagca ctctacaaaa
gcttggcagc gagattgggg catgaaacag ctttcgcaac 8040tttagtggta aaatggttgg
cttttggggg cgaaacggta tctgcccata tcaagcaagc 8100agcagttgat ttactagtgt
attatatcat gaacaaacca tcttttcctg gagacacaga 8160gacccaacaa gaggggagga
ggtttgtagc tagtcttttc atatctgcgc tagcgacata 8220cacatacaaa acctggaatt
acaacaatct ggcgcgggtc gttgagcctg ccttagctta 8280cctcccatat gctacaagtg
ccttgaagtt gttcacacct acaagattag agagtgtggt 8340catactcagt tctacaatct
acaagacgta cctctctata aggaagggca agagcgacgg 8400cctactgggt acaggtataa
gtgcagccat ggagatctta aaccaaaacc caatctcagt 8460tggtatatct gtgatgctgg
gggtgggtgc tattgccgcc cataatgcaa tagmatccag 8520tgaacagaaa agaactttgt
tgatgaaagt ctttgtaaaa aacttcttgg accaggcagc 8580aacagatgag ctagtcaaag
agaaccccga aaaaataatc atggctctgt ttgaagcagt 8640ccagaccata ggcaaccccc
taagactcat ctaccatctg tacggggtat actataaggg 8700gtgggaagca aaagaactcg
cagaaaaaac tgccggccgc aacttattta cactgatcat 8760gtttgaagcc tttgaacttt
taggtatgga ctcagaaggg aagataagaa acttgtcagg 8820taactacata ctggacttga
ttttcaattt rcataataaa ttaaacaagg gactcaaaaa 8880gttggtcctt ggctgggccc
cagcaccttt tagctgcgat tggacaccaa gtgatgagag 8940gataagccta cctcacaaca
actacttaag ggtggaaacc aagtgtcctt gcggctatga 9000gatgaaggca ataaaaaacg
ttgctggcaa attgacaaaa gttgaagagr aagggccctt 9060cctttgcaga aacagattag
ggagaggacc tccaaacttc aaagtaacaa aattctatga 9120tgacaatttg atagaagtta
agccagtagc taggtcagaa ggccaagtgg atctctacta 9180caagggagta acagcaaggt
tagactatag taacgggaaa gtgctgttag ctaccaacaa 9240gtgggaggtg gaccacgctt
ttctgactag actagtaaag aagcacacag ggataggttt 9300taaaggtgca tatttgggtg
accgaccaga ccatcaagat cttgtcagta gagattgtgc 9360aaccataact aagaactcag
tacagtttct gaaaatgaag aagggttgcg cttttacata 9420tgacctaaca atctctaacc
ttgtcaggct tattgaacta gtccacaaga atgatttaca 9480agagagagaa atcccaactg
tgacagtaac tacctggctt gcttattctt ttgtcaacga 9540agacctgggg actatcaagc
ctgtgttggg ggagaaagtc atcccagaac cccccatgga 9600gttgagtctt caacccgctt
tgggactggt taccaccgaa acagcgataa ccataacagg 9660ggaggctgaa gtgatgacga
cagggatcac accagtggta gaaatgaaag aagaacctca 9720gctgggccat cagtcaacta
ccctaaaggt agggttgaag gaaggggaat tcccagggcc 9780aggagtcaac cctaaccatt
tagtagargt gatagatgaa aaagatgtca ggccttttgt 9840cctagttatc gggaataaag
gttctacctc aaatagagca aaaacagcca agaatatacg 9900tttgtacaaa ggaaacaatc
caagagagat caggtatctg atgagccaag ggagaatatt 9960aacggttgct ctaaaagagt
tggacccgga attaaaagag ttggtagatt ataaggggac 10020ctttctcaat agggaagctt
tagaagcact aagcttaggt aaaccaatca agaggaaaac 10080cacaacagca atgatcagga
ggttgataga gccagaggtt gaggaggaac taccagattg 10140gttccaagcg gaagaacccc
tatttttgga agcaagaatc maggctgaca tttatcacct 10200agtgggcagt gttgacagta
taaaaagcaa agcaaaggaa ttgggggcca cagataacac 10260aaagrttgtg aaggaggtcg
gggctaggac ctatactatg aaattgagca gttggagtac 10320acaagttacc aaaaaacaaa
tgagtctagy cccccttttt gaagagctgt tattaaagtg 10380tcctccatgt agcaaaattt
caaagggaca tatggtgtca gcataccaac tggcccaagg 10440aaactgggaa cccctcgggt
gtggggttta tatggggact gtaccagcta ggcgtctcaa 10500gatccaccct tacgaggctt
acctcaaact caaagagctg gtggaaggtg aactttcaag 10560ggttaccgca agagaatcca
tcataagaga acataacact tggattttgc ggaaagtgag 10620acacgaaggg aacctaagaa
ctaaatcaat gattaaccct gggaaagtat cagaacagtt 10680gtgcagagaa ggacacaaaa
gaaacatata caacaagatt ataggctcaa caatggcctc 10740tactggtatc aggctggaga
aactgccaat agtccgagcc caaactgata caaccagttt 10800ccaccaagct ataagagaga
aaattgataa gccagaaaac aagcaaaccc ctgaattgca 10860tgaagagcta aagaaggttt
ttgactgctt aaagatcccg gagctgaagg aatcgtatga 10920tgaagtttca tgggaacaat
tagaagccgg gataaaccgc aagggagcag ccggttttct 10980agagagtaag aacatagggg
aggtgctgga cacggaaaaa cacatagtag aacaattaat 11040cagggatctg aggcagggga
agaagatcag gtattatgaa acagccatcc ccaagaatga 11100gaagagagat gtcagtgacg
actgggaagc cggagaattt gttgatgaga agaaaccaag 11160agtaatccag tacccagatg
ccaaggtgag actggccatc acaaaagtaa tgtacaagtg 11220ggtgaagcaa caaccagtgg
tgatacccgg ctatgagggt aaaacaccgc tatttgatat 11280attcaacaag gtgaagaagg
aatgggattc attccaggac cctgtagcgg tgagctttga 11340caccaaagcc tgggatacac
aagttactag tagagaccta atgttgataa gggacatcca 11400gaaatattat ttcaagagaa
acatacacaa atttttagat acaataacag aacacatggt 11460ggaggtaccc gtcattacag
cagacggtga agtttacata aggaatggtc agaggggtag 11520tggccaaccc gacacaagtg
ctggtaacag tatgttgaat gtcctaacca tgatatatgc 11580cttctgtaaa agcacaggta
taccttacag gggattcagc agagtggcaa gaatccatgt 11640gtgtggtgat gatggctttt
tgataacaga aagagggctg gggttgaaat tctctgagaa 11700gggtatgcag atattacatg
aggccgggaa gccccagaaa ataactgaag gggacaaaat 11760gaaagtggca tacagattcg
aggacattga gttctgttcc catactcctg tgccagtcag 11820atgggcagat aacaccagta
gttacatggc agggaggagt acagctacta tactagctaa 11880gatggcaacc aggctggatt
ccagcggaga gaggggtagc acagcttatg agaaggccgt 11940agcctttagc ttccttttga
tgtactcatg gaatccggtg gttagaagga tctgcttaat 12000ggtgttgtca cagtatccgg
aagtatcccc atccaaacat acaatatact actaccaagg 12060ggatcccata gctgcataca
gagaagtgat agggagacag ctgtgtgaac tgaaaagaac 12120aggatttgag aagctagcta
gcctgaacct gagtatgacc actctaggca tctggacaaa 12180acatactagt aaaagactaa
tccaagactg tgtagaaata ggtaagagag aaggtaattg 12240gttagttaat gctgacagac
tgatttcagg aaagactggg aagttttata tcccaaacac 12300tggtgtcacg ctattgggaa
aacattatga ggaaattaac ttaaagcaaa aggcggcaca 12360accgccgacg gaaggggttg
acagatataa gttgggcccc atagttaata ttattttgag 12420aagattgagg gtaatgctaa
tgacagtggc cagcggaaac tggtaaacct gtccagagcg 12480cagcgctctc actcaaggta
tttaattgta aatattgtaa atagacagct aagatattta 12540ttgtagttgg aaagtaatat
agtgatagca aataccccaa tctaacacta cctccaacgc 12600actaagcact ttagctgtgt
gaggttaact cgacgtccat ggttggacta gaggragcct 12660ctagc
12665212229DNABovine Viral
Diarrhea Virus Type II 2gagagccttt tctaattctc gtatacrtat tgggcaatta
aaataataat taggcctagg 60gaacaaaagt ccccctcagc gaaggccgaa aagaggctag
ccatgccctt agtaggacta 120gcataaagag gggggtagca gcagtggtga gttcgttgga
tggcttaagc cctgagtaca 180gggtagtcgt cagtggttcg acgccttgga ataaaggtct
cgagatgcca cgtggacgag 240ggcatgccca aagcacatct taacctgagc gggggtcgcc
caggtaaaag cagttctaac 300cgactgttac gaatacagcc tgatagggtg ctgcagaggc
ccactgttct gctactaaaa 360atctctgctg tacatggcac atggagttga tcacaaatga
acttttatac aaaacttaca 420aacaaaaacc cgtcagggtg gaagaacctg tttatgatca
ggcaggtgat cccttatttg 480gtgaaagggg agcagtccac cctcaatcga cgttaaagct
cccacacaag agaggggaat 540gcgatgtacc catcaacttg gcatctttac caaaaagggg
tgactgcagg tcgggtaata 600gcagaggacc tgtgagcggg atctacttga agccagggcc
actattttac caggactata 660agggtcccgt ctatcacagg gccccgctgg agctctttga
agagggaacc atgtgtgaaa 720cgactaaacg gatagggaga gtaactggaa gtgacggaaa
gttgtaccac atttatgtgt 780gtatagatgg atgtataata ataaaaagtg ccacaagaag
tcaccaaagg gtgcttaggt 840gggtccataa taggcttaac tgccctctat gggtcacaag
ttgctcagac acgaaagaag 900agggagcaac aaaaaagaaa acacagaaac ccgacagact
agagaagggg aagatgaaaa 960tagtgcccag agaatccgaa aaagacagca aaactaaacc
tccggatgct acaatagtgg 1020tagatggagt taaataccag gtgaagaaga agggaaaaat
caagagtaag aacactcagg 1080acggcttgta ccataacaaa aacaaaccgc cggaatcacg
taagaaactg gaaaaagcat 1140tgctggcatg ggcaataata actatagttt tgtttcaagt
tacaatggga gaaaacataa 1200cacagtggaa cctacaagac aatgggacgg aagggataca
acgggcaatg tttcaaaggg 1260gtgtgaatag aagtctacat ggaatctggc cagagaaaat
ctgtactggt gtcccttccc 1320atctagccac cgatatggaa ctaaaaacaa tccatggtat
gatggatgca agtgagaaga 1380ccaactacac gtgttgcaga cttcaacgcc atgagtggaa
caagcatggt tggtgcaact 1440ggtacaatat tgaaccctgg attctagtca tgaatagaac
ccaagccaat cttactgagg 1500gacaaccacc aagggagtgc gcagtcactt gcaggtatga
tagggatagt gacttaaacg 1560tagtaacaca agctagagat agccccacac tcttgacagg
ttgcaagaaa ggaaagaact 1620tctcctttgc aggcatactg acgcggggtc cctgcaactt
tgaaatagct gcgagtgatg 1680tattattcaa agaacatgac tgcactagta tgttccagga
tactgctcat taccttgttg 1740acgggatgac caactcctta gaaaatgcca gacaaggaac
cgctaaactg acaacctggt 1800taggcaagca gctcgggata ctagggaaaa agttggaaaa
caagagtaag acgtggtttg 1860gagcatacgc ggcttccccc tactgtgatg tcgatcgaaa
gattggctac atatggtata 1920caaaaaattg tacccctgcc tgcttgccca agaacacaaa
aattgtcggc cctgggaagt 1980ttgacaccaa cgcagaggaa ggcaagatac tacatgagat
ggggggccac ttgtcggagg 2040tactactact ttctttagtg gtgctgtccg acttcgcacc
ggaaacagcc agcgcaatgt 2100acctaatcct acatttttcc atcccacaaa gtcacgttga
cataatggaa tgtgataaga 2160cccagttgaa cctcacagtg gagcttacaa cagctgatgt
aataccagga tcagtctgga 2220acctaggcaa atgggtatgt ataagaccaa attggtggcc
ttatgagaca actgtggtgt 2280tggcatttga agaggtgagc caggtggtga agttagtgtt
gagggcactc agagatttga 2340cacgcatttg gaacgctgca acaactactg ctttcttaat
atgccttgtt aagatagtca 2400ggggccagat ggtacagggc attctgtggc tactactgat
aacaggggta caaggggact 2460tgcattgcaa acctgaattc tcatatgcca tagcaaggga
tgaaagaatt ggtcaactgg 2520gggctgaagg ccttactacc acttggaagg attactcgcc
tgaaatgaaa ctggaagaca 2580caatggtcat agcttggtgc aaagatggta agtttacgta
cctcccaagg tgcacgagag 2640aaaccagata tctcgcgatc ttgcatacaa gggccttacc
gaccagtgtg gtattcaaaa 2700aactttttga tgggcgaaag caagaggatg tagtcgaaat
ggacgacaac tttgaatttg 2760gactctgccc atgtgatgcc aaacccatag taagagggaa
attcaataca acgctgctga 2820acggaccggc cttccagatg gtatgcccca taggatggac
agggactgta agctgtatgt 2880cattcaatat ggacacctta gccacaaccg tgatacggac
atatagaagg tccaaaccat 2940ttcctcatag gcaaggctgt atcacccaaa agactctggg
ggaggatctc cataactgca 3000tcctcggagg aaattggact tgtgtgcctg gagacatgct
attatacaaa gggggctcta 3060ttgaatcctg caagtggtgt ggttatcaat ttaaagagag
cgagggacta ccacactacc 3120ccattggcaa gtgtagatta gagaatgaga ctggttacag
actagtagac gatacctctt 3180gtaatagaga aggtgtggcc atagtaccac aagggacatt
acggtgcaag ataggaaaaa 3240ctactataca ggtcatagct atggatacca aactcgggcc
tatgccttgc agaccatatg 3300aaataatatc aagtgagggg cctgtagaaa ggacagcgtg
taccttcaac tacactaaaa 3360cattaaaaaa taagtatttt gagcccagag acagctactt
ccagcaatac atgctaaaag 3420gagagtatca atactggttt gacctggagg taaccgacca
tcaccgggat tactttgccg 3480agtccatatt agtggtggtg gtagccctcc tgggtggcag
atatgtactt tggttactag 3540ttacatacat ggtcttatca gaacagaagg cctcagggac
tcagtatgga gcaggggaag 3600tagtgatgat gggcaacttg ctaacccata atgacattga
agtggtgaca tacttcttgc 3660tgttgtacct actgctgagg gaagagagcg taaagaagtg
ggtcttactt ttataccaca 3720tcttagtgtc acacccaatc aaatctgtaa ctgtgatcct
attgatgatt ggggatgtgg 3780taaaggcaga ctcagggggc caagggtact ttgggcaaat
agacctctgt tttacaatag 3840ttgtactaat catcataggt ttaatcatag ccaggcgtga
cccaactata gtgccactag 3900taacaataat ggcagcactg agggtcactg gattgaccta
ccagcctgga gttgacgtcg 3960ctatggcagt catgaccata accctactga tggttagcta
tgtgacagat tactttagat 4020ataaaagatg gttacagtgc gttctcagcc tggtgtcagg
ggtgttcttg ataagaagcc 4080taatgcacct aggtagaata gaggtgccag aggtaaccat
cccaaactgg agaccactaa 4140ctttaatact gttatatttg atctcaacaa caattgtaac
aatgtggaag gttgacatcg 4200ctggcttgtt gttgcaatgc ctgcctatct tattactggc
cacaaccttg tgggccgact 4260tcttaaccct catactgatc ctgcctacct atgaattggt
taaattatac tacctgaaaa 4320ctgttaggac tgatatagaa agaagttggc caggggggat
agactgtaca agagttgact 4380ccatctacga cattgatgag agtggagagg gcgtatatct
ctttccatca aggcagaaag 4440gacagaggag cttttccata ctcttgcccc ttgtcaaagc
aacactgata agttgcgtca 4500gcagtaaatg gcagctaata tacatgagtt acctaacttt
ggactttatg tactacatgc 4560acaggaaagt tatagaagag atatcaggag gcaccaacat
gatatccagg ttagtagcgg 4620cactcataga gctgaactgg tccatggaag aagaggagag
caaaggccta aagaagtttt 4680atctattatc tggaaggttg agaaacctaa taataaaaca
taaagtaaga aatgagaccg 4740tggcttcttg gtacggggag gaggaagtct acggtatgcc
aaagatcatg acaataatca 4800aggccagtac gctgagtaag agcaagcact gcatgatatg
cactgtatgt gagagccgag 4860agtggaaagg cggcacctgc ccaaaatgtg gacgccatgg
gaagccgata atgtgtggga 4920tgtcgctagc ggattttgaa gaaagacact ataaaagaat
ctttataagg gaaggtaact 4980ttgagggtcc tttcaggcaa gaatacaatg gctttgtaca
atataccgct agggggcaat 5040tacttgtgag aaacttgccc gtactggcaa ctaaagtaaa
aatgctcatg gtaggcaacc 5100ttggagaaga aattggtgat ctggaacatc ttgggtggat
cctaaggggg cctgccgtgt 5160gtaagaagat cacagagcac gaaaaatgcc acatcaatat
actggataaa ctaactgcat 5220ttttcgggat catgccgagg gggactacac ccagagcccc
ggtgaggttc cctacgagct 5280tactaaaagt gaggaggggc ctggagactg gctgggctta
cacacaccaa ggtgggataa 5340gttcagtcga ccatgtaacc gccggaaaag acctattggt
ctgtgacagc atgggacgga 5400ctagagtggt ttgccaaagc aacaacaggt tgaccgatga
gacagaatat ggcgtcaaga 5460ctgactcagg atgcccagac ggtgccagat gttatgtgtt
aaatccagag gctgtcaaca 5520tatcaggatc caagggggca gtcgtccacc tccaaaagac
aggtggagaa ttcacgtgtg 5580tcaccgcatc aggcacaccg gcctttttcg acctaaaaaa
cttgaaagga tggtcaggat 5640tgcctatatt cgaagcctcc agcgggaggg tggttggcag
agtcaaagta gggaagaatg 5700aagagtctaa acctacaaaa ataatgagtg gaatccagac
cgtctcaaag aacacagcag 5760atctaactga gatggtcaag aagataacca gcatgaacag
gggagacttc aagcagatta 5820ctttggcaac aggggcagga aaaaccacag aactcccaaa
agcagttata gaggaaatag 5880gaagacacaa gagagtatta gttcttatac cattaagggc
agcggcagag tcagtttacc 5940agtatatgag attaaaacac ccaagcatct cttttaacct
aaggataggg gacatgaaag 6000agggggacat ggcaacgggg ataacctatg catcatacgg
gtacttctgc caaatgcccc 6060aaccaaagct cagagctgct atggtagaat actcatacat
attcttagat gaataccatt 6120gtgccactcc tgaacaactg gcaattatcg gaaagatcca
cagattttca gagagtataa 6180gagtcgtcgc catgactgcc acgccggcag ggtcggtgac
cacaacaggt caaaagcacc 6240caatagagga attcatagcc cccgaggtaa tgaaagggga
ggatcttggt agtcagttcc 6300ttgatatagc agggttaaaa ataccagtgg atgagatgaa
aggtaatatg ttggtttttg 6360tacccacgag aaacatggca gtagaggtgg caaagaagct
aaaagctaag ggctataatt 6420ctggatacta ttacagtgga gaggatccag ccaatctgag
agttgtaaca tcgcagtctc 6480cctatgtaat cgtggccaca aatgctattg aatcaggagt
gacactacca gatttggaca 6540cggttgtaga cacggggctg aaatgtgaaa agagggtgag
ggtatcatca aagataccct 6600tcatcgtaac aggtcttaag aggatggccg tgactgtggg
tgagcaggct cagcgtaggg 6660gcagagtagg tagaatgaaa cccgggagat attatagaag
ccaggaaaca gcaaccgggt 6720caaaggacta ccactatgac ctcttgcagg cacaaagata
cgggattgag gatggaatca 6780acgtaacgaa gtcctttagg gagatgaatt acgattggag
cctatacgag gaggacagcc 6840tactaataac ccagttggaa atactaaata atctactcat
ctcagaagac ttgccagccg 6900ctgttaagaa tataatggcc aggacagatc acccagagcc
aatccaactt gcatacaaca 6960gctatgaagt ccaggtcccg gtcctgttcc caaaaataag
gaatggagaa gtcacagaca 7020cctacgaaaa ttactcgttt ctaaacgcca gaaagttagg
ggaggatgta cccgtgtata 7080tctatgccac tgaagatgag gatctggcag ttgacctctt
agggctagac tggccagatc 7140ctgggaacca gcaggtagtg gagactggca aagcactgaa
gcaagtgacc gggttgtcct 7200cggctgaaaa tgccctacta gtggctttat ttgggtacgt
aggttatcag gctctctcaa 7260agaggcatgt cccaatgata acagacatat ataccatcga
ggaccagaga ctagaagaca 7320ccacccacct ccagtatgca cccaacgcca taaaaaccga
agggacagag actgaactga 7380aagaactggc gtcgggtgac gtggaaaaaa tcatgggagt
catttcagat tatgcagccg 7440ggggactgga gtttgtgaaa tcccaagcag aaaagataaa
aacagcacct ttgtttaaag 7500aaaacgtaga agctgcaaaa gggtacgtcc aaaaattcat
tgactcatta attgaaaata 7560aagatgcaat aatcagatat ggtttgtggg gaacacacac
tgcactatac aaaagcatag 7620ctgcaagact ggggcacgaa acagcgtttg ccacactggt
gttaaaatgg ctagcttttg 7680gaggggaatc agtgccagac cacatcaagc aggcggcagt
tgatttagtg gtctattatg 7740tgatgaataa gccttccttc ccaggcgaca ccgaaacaca
gcaagaaggg aggcgattcg 7800tcgctagcct gttcatctcc gcactggcaa cctacacata
caaaacttgg aattaccaca 7860atctctctaa agtggtggaa ccagccttgg cttacctccc
ctatgctacc agcgcattaa 7920aaatgttcac cccaacgcgg ctagagagcg tggtgatact
gagcaccacg atatacaaaa 7980catacctctc cataaggaag gggaagagtg atggattgct
gggcacgggg atcagtgcag 8040ccatggaaat cctgtcacaa aacccagtgt cggtgggtat
atctgtgatg ttgggggtag 8100gggccattgc tgcgcacaac gctattgagt ccagtgaaca
gaaaaggacc ctacttatga 8160aggtgttcgt aaagaacttc ttggatcagg ctgcaacgga
tgagctggta aaagaaaacc 8220cagagaaaat tataatggcc ttatttgaag cagtccagac
aattggtaac cccctgagac 8280taatatacca cctgtatggg gtttactaca aaggttggga
ggccaaggaa ctatctgaga 8340ggacagcagg cagaaactta ttcacattga taatgtttga
agccttcgag ttattaggga 8400tggactcaga aggaaaaata aggaacctgt ccggaaatta
catcttggat ctgatatacg 8460gcctacacaa gcagatcaac agagggctga agaaaatagt
actggggtgg gctcctgcac 8520cctttagttg tgactggacc cctagcgacg agaggatcag
attgccaaca gacaactatt 8580tgagggtaga aaccaggtgc ccatgtggtt atgagatgaa
agcgttcaaa aatgtaggtg 8640gcaagcttac caaagtggag gagagcgggc ctttcctatg
tagaaacaga cctggtaggg 8700gaccagtcaa ctacagagtc accaagtatt acgatgacaa
cctcagagag atagaaccag 8760tagcaaagtt ggaaggacag gtggagcact actataaagg
ggtcacagca aaaattgact 8820acagtaaagg aaaaacgctc ttggctactg acaagtggga
ggtagaacat ggtgtcatga 8880ccaggttagc taagagatat actggggttg ggttcaatgg
tgcatactta ggtgatgagc 8940ccaatcaccg tgatctagtg gagaggaact gtgcgactat
aaccaaaaac acagtacagt 9000ttctaaaaat gaagaagggg tgtgcattca cctatgacct
gaccatctcc aatctgacca 9060ggcttattga actagtacac aggaacaatc ttgaagagaa
ggaaataccc accgttacag 9120tcaccacatg gctagcttac accttcgtga atgaagacgt
agggactata aaaccagtac 9180taggagagag ggtaatcccc gaccctgtag ttgatgtcaa
cttacaacca gaggtccaag 9240tggatacatc agaggtcggg atcacaataa ttggaaggga
aaccctgatg acaacggggg 9300tgacacctgt attggaaaaa gtagagcctg acgctagcaa
caaccaaagc tcagtgaaga 9360ttgggttgga taagggtaat tacccagggc ctggaataca
gacacataca ctaacagaag 9420aaatacacga cagggatgca agacccttca tcatgatcct
gggctcaaag aattccatgt 9480caaatagggc aaagactgct agaaacataa atctgtacac
aggaaatgac cccagggaaa 9540taagagactt gatggctgca gggcgcatgt tagtagtagc
actgagggat gtcgaccctg 9600agctttctga aatggtcgac ttcaagggga ccttcttaga
tagggaggcc ctggaggctc 9660taagtctcgg gcaacctaaa cctaagcagg tcaccaaggc
agctattagg gatttgattg 9720aacaggaaaa acaggtggag atccctaact ggtttacatc
agatgaccca gtatttttgg 9780aagtggccat aagaaatgat aagtactact tagtaggaga
tgttggagag gtaaaagatc 9840aagctaaaac acttggggcc acggatcaga caagaattgt
aaaggaggta ggctcaagga 9900cgtataccat gaagctatct agttggttcc tccaagcatc
aaaaaaacag ataagtttaa 9960ctccactgtt tgaggaattg ttgctacggt gcccacctgc
aactaagagc aataaggggc 10020acatggcatc agcttaccaa ttggcacagg gtaactggga
gcccctcggt tgcggggtgc 10080acctaggtac cataccagct agaagggtga agatacaccc
atatgaagct tacctgaggt 10140tgaaagattt catagaagaa gaagagaaga aacctagggt
taaggataca gtaataagag 10200agcacaacaa atggatactt aaaaaaataa ggtttcaagg
aaacctcaac accaagaaaa 10260tgctcaaccc cgggaaacta tctgaacagt tggacaggga
ggggcgcaaa aggaacatct 10320acaaccacca gattggtacc ataatgtcaa gtgcaggcat
aaggctggag aaattgccaa 10380tagtaagggc ccaaaccgac actaaaacct ttcatgaggc
aataagagat aagatagaca 10440agagtgagaa ccggcaaaat ccagaattgc acaacaaatt
gttggagatt tttcacacaa 10500tagcccaacc cgccctgaaa cacacttacg gtgaggtgac
gtgggagcaa cttgaggcag 10560ggataaatag aaaaggggca gcaggctttc tggagaagaa
gaacatcggg gaagtattgg 10620attcagaaaa acacctggtg gaacaattgg tcagggatct
gaaggccggg agaaagataa 10680aatattatga aactgcaata ccaaaaaatg agaaaagaga
tgtcagcgat gactggcagg 10740caggggacct ggtggatgag aagaggccaa gagttattca
ataccctgaa gccaagacaa 10800ggctagccat cactaaggtc atgtataact gggtgaaaca
gcagcccgtt gtgattccag 10860gatatgaagg aaagacccct ttgttcaaca tctttgataa
agtgagaaag gaatgggact 10920tgttcaatga gccagtggcc gtaagttttg ataccaaagc
ctgggacaca caagtgacta 10980gtagggatct gcaacttatc ggagaaatcc agaaatatta
ctataggaag gagtggcaca 11040agttcattga caccatcacc gaccacatga cagaagtgcc
agttataaca gcagatggtg 11100aagtatatat aagaaatggg cagagaggta gtggccaacc
agacacaagt gcaggcaaca 11160gcatgttaaa tgtcctaaca atgatgtacg ctttctgcga
aagcacaggg gtcccgtaca 11220agagtttcaa cagggtggca aggatccatg tctgtgggga
tgatggcttc ttaataactg 11280aaaaagggtt agggctgaaa tttgctaaca aagggatgca
gattcttcac gaagcaggca 11340aacctcagaa gataacggaa ggggaaaaga tgaaagttgc
ctatagattt gaggacatag 11400agttctgttc ccatacccca gtccctgtta ggtggtccga
caataccagt agtcacatgg 11460ccgggagaga caccgctgtg atactatcaa agatggctac
aagattggat tcaagtggag 11520agaggggtac cacagcatat gaaaaagcgg tagccttcag
tttcttgctg atgtattcct 11580ggaacccgct tgttaggagg atttgcctgt tggtactttc
gcaacagcca gagacagacc 11640catccaaaca ggccacttat tattacaaag gtgatccaat
aggggcctat aaagatgtga 11700taggtcggaa tctaagtgaa ctaaagagaa caggcttcga
gaaattggca aatctaaacc 11760taagcctgtc cacattaggg atctggacta agcacacaag
caaaagaata attaatgact 11820gtgttgccat tgggaaagaa gaaggcaact ggctagttaa
cgccgacagg ctgatatcca 11880gcaaaactgg ccacttatac atacctgata agggctttac
attacaagga aagcattatg 11940agcaactaca gctaagaaca gagacaaacc cggtcatggg
ggtcgggact gagagataca 12000agttaggtcc catagtcaat ctgctgctga gaaggttgaa
agttctgctc atgacggccg 12060tcggtgccag cagctgagac aagtgtatat attgtaaata
aattaaccca tgtacatatt 12120gtatataaat atagttggga tcgtccacct caagaagacg
acacacccaa cacgcacagc 12180taaacagtag ttaagattat ctacctcaag ataacactac
atttaatgc 12229311105DNABovine herpesvirus 1misc_featureIRL
Region 3gccccgagac ccccggccct gaggccctgg ggcggggccc gactgtcccc ttcccccctc
60ccccccgtcc gcccgcgagt aaaggctgtc taattttttc cgcacgcccg cgcctgtctt
120cttagggagg ggaaggaggg gagggagggg aaggagggga ttcgggccgg ccgaggattc
180gggccggccg agcgagcggg ccaaagctcc ggctccccct tccccctccc gccccgcggg
240cgaataaaac aactagaacc acaagatata gagaggcaag gcgcgcctgc gcgcggcgtt
300ttatttaaaa aaatatgaca agggccgggg agagggcggg agagggggcc gcggggcccc
360gcccccctaa actcgctggc ggcgcttggc cggcgcgggc cgcgcccggg cgcgaccgga
420gggcgagccc cccggcgacg ggtatggcga ggagcccggc gaggagccgg aggaccagcg
480ccagcagggc gcgggccggc gccggcccgc gcgcgcgggg gggccgccgg cgccgggccc
540ggcgccggcc gggcgcgggt ccccgggccc ggggaagaac acgtcgtcgt cgccgtccga
600ggcggagaac gaggacagcg acgacgagga ggtggaagag gacgcggtgg gcgacgagac
660gaaggagacg gccgaggccg cgggcgaggc ggaggagagg accgcggctc gcgcgcggca
720ccggggggcg ctttcggcgg cggccccctc gccgccgttc tcctccccct cctcgtccgc
780ctcctcgtcc tcctcgtagt cttcgctgct ggagtcgctg ccgctcacgt cgcactcggc
840tccgaaaagc gggcccggca ggcgcgccgg gggcgacagc gggcgcgccc tgggcccggc
900ggcggcggcg gcgcgcaaaa gccggcgcag cgggccggcc tgctcgggcg agagctgcag
960cagcgcctcc cagcacgcgt ccgtgggcgt ggcgcccgtg tagccgagca ggaagaagcc
1020gacgagcgcg cggcgcagcg cgcgcgtgtc ggccgtgacg aacgcggagc cggtggcgat
1080gcagcggaag agggtgttga cgtcgatggc gaggcgcagc gcctcggggc gccagtcctc
1140ggggcagaag gcgcccgggc cgcggcgagc gtgctcgtcc gcgggggcgg ggcccgagac
1200cacgcggtcg ggcgagcggc agaggcggca ggagccgtcg caggtggggc aaggctggcc
1260gtggctcatg gcggcggcgg gccgggccgg tctgccggga caaagggggc gggacagaga
1320agaggaggag cggtaagcgg gcgccccggg gcagggcccg cccggtcgcg tggcaagcga
1380gtggccgcgc agggcgcgtc cggggagggc gggcttgccc cgggcgggcg agggatcggg
1440gggatggggg cgagggatcg ggaggatggg ggcgagggat cggggggatg ggggcgaggg
1500atcgggggga tgggggcgag ggatcggggg gatgggggcg agggatcggg gggatgggga
1560tggggggcga ggggaacctg gcttacctcg caatgtcgcc ctggtccacc ggcgcggtcc
1620tgggtttcag ctctgggggg tcgccgccgg ggttctgcaa gagcatggct gggctgggct
1680gggctggggt gggctgggct gggctgggct ggggtgggct ggggtgggct gggctgggct
1740ggggtgggct gggctgggct gggctgggct ggggtgggct ggggtgggct gggctgggct
1800gggctgggct ggggtgggct gggctgggct ggggtgggct gggctggggt gggctgggct
1860ggggtgggct gggctggggt gggctgggct ggggtgggct gggctgggct ggggtgggct
1920gggctgggct ggggtgggct gggctgggct ggggtgggct gggctgacct tgcggcaggt
1980ccctaggtgc agtcgaggtg cggttcctgg aggtgctcgt caagccggct gcgatggagc
2040gctgcacggg ggggtggggg cggagcacag gagctcgggt ggggtcccga gtgagctccg
2100cccacccagc ccccaccccc gtctgcccgc ccccgggccc gagatgaggg tgggggctgg
2160gtgggcggag ctcacttggc ggggtcgtcg gcggggcgtc cggggtcgtc ggcggggcgt
2220ccggggtcgt cggcgagttc ctatggaagc aacccacctg agctcgagga agcggttcgc
2280tcgagctcgg gtgggggtgg gggtgagcga gaaaaaaaaa aaaaaaaaaa aagggccccg
2340gccccggggc ggatgcgctt accttgcctt tgccggggct ggggatcggt gaaggttctg
2400cagtgcgccg cgctcctcta gctccccgtg tgtgggcttg gggcgcgatg tcgcgcgctt
2460atatgtcttt gagtagggcg ctcctccccc cgcccccggc cgagcgccgc ccctggcccg
2520gcctgatttg cctgtgccct cccaccgtcc cggtagccct ctcgggaccc cacgtgagaa
2580cactggcaga atgccagggg gcccacgtaa ggggccccgc ccccggccga gcgccgcccc
2640cggcccggcg ccgcctccga cccggcgccg cctccgaccc gacatgattt gcatatgccc
2700tcccactatc ccggcagccc catcgaaacc cggcgttggt ggttgccatg ggcaggcttg
2760gcgccagtcc cagaattcgc actcgggcta ataatatata tatacttatt gagttttgtg
2820cgaacgctgg cattctgcca gcgttctcac gggcacggtc gtgagagctg gcgcgggtcc
2880cagggctcgc actcgggcca ataatatata tataaactta ttgagctttg tgcgaacgct
2940ggaggccagc caagcagccc cgcgaggctc gtcggcccgc ccgccccgcg gttgtagggg
3000tcacgtgggt cggcgcctcg ccgtggtgga caggcccccc cgctggcgca aaaatacaat
3060agctctcgat tatccgccat tggatttttt gcccgcgcgg gggcgctgtc caggtggagg
3120ggggcccgag cagggcccta aaaacccgca tggcgcgaag tccggcgcgg cgcgcgcggg
3180agggtcttcc tctcttcata atcaatccgc caatcgattt gggtctggcg gcccaaacgg
3240cccgatacat cgatcgcgct tacagatcaa tcgtattgat ttaatctgat ggcccgatac
3300caatctatca atatcggtta gatcgattgc caattgtaca accggccgca tatgcgcccc
3360gttaatcgat cgaccctcgc cgatatttat tttcgccgat tggactttaa agtttcagct
3420attgatcatc tattgaccga aactgtgtgt cgatatccct ctctgtggtc cctccacccc
3480ccaccccgca tcaatccagc cgcgcccgag taacaggggg gaggggaggg gggcataaaa
3540ggacgaatag aaactcaggg ggggctacga cccgagtggg aggggatggc gccatctggt
3600ggcgacgcgc aaaataacgg cacccaaaaa gggtgcgggt cgctgcaagt acgccccccc
3660ccataaaggt acagcagctg cggcggcttg cccagcaggt ggcgcagcaa cagagccatc
3720aatacagatc tttttttttt gtttcgcccc gcctctccgt gcacttacac agctaaaccg
3780caaggcggag caaggaacga tggggggggg caggggcaag ctgagcgagc aagcgagcgc
3840agagagaaga gagcgggcgg cggccgcggc tgcctggagc cgaagcggat gaaccgcccg
3900ggcgagcgag cacgacacgc ccaaaggggg gggcaagacc ggcaaggtgg gctgcggctt
3960gcatgcaagg acacgggata gtgggctggg ggtatgcccg gcaagggggt cagcagcggg
4020gtgggaagct gcggtggtcg tccacagggg cgcgggtgtg catatacaaa ctacccacgc
4080cggcaagctg atggcagggg gcggcggcgg ggcggagggg gaccgcggaa gcactgcggg
4140ccagggggct atgcaaatta aaccgggcag gggcgagcca aatgcaaaag cgcaaggcgg
4200gccaaagcaa gcgccacccc ccaactcccc gcttttgtta tcgccgcgcc tgcttgctct
4260cccttttttt ggtttttttt taaaaaaagg ggggttgtca ggttacggtt agtttcctcc
4320cccgccattt tcttttcgcc tctgctgctc ctttttcctc ctccccattt tcctcctcct
4380tccccccccc cccgctagca caggcttgag ggaacactgt gttcctcgca taaggcgccg
4440cggctgggcc cttcacacag gcaaaagtgg ggaagcaggg ccgcggcgag taatttgcgg
4500ttagaacagg tcgcgccctc gcaccggcgg ctgtggctca ggcttttccc cttgggacac
4560acgcccggag gcaactggta cactgtgtgg cgatctcgca aatgcagcaa gggaggagga
4620gcggggtgcg gggtgcgagg gggagggggg gtggtggccg tggagagaat ggagcggcta
4680gggccaaagg gggcagcggg cggtcagacc agggcgggcg ggcgggcgcg caggcgcgca
4740caaaaagggc caaccaccaa aactaaatgc cgcgcaaata ggcaaaagga aaaggcgggc
4800tcgaaggcaa tgctgggggc ggagggagca gtggcgctgg gcaggaagcg gggagtccca
4860atggggaggg ggtaggcaaa tgagcctgga cacaattgcc gcgcctccct gctcgctcac
4920cgccggggtc ctgggcggga agcggggagt cccaatgggg agggggtagg caaatgagcc
4980tggacacaat tgccgcgcct ccctgctcgc tcaccgccgg ggtcctcccg ccaatcgcga
5040aagggagaag ggtggggggc ggccgtgagc aagcggggaa gaagggggaa gggggaagga
5100ggggaggcta gaagcagcgg gcgggacgcg cgtcggtccg gccggcccca tcccgcctag
5160cgggctggcc agaccaacgc gcgcgaggca ggggcgggaa tggggagggg aactggtagg
5220ggcgggcctg gtgcaaggcg ggcctgccgg gcgcggggcc gggggcgttc ggccatgctt
5280tcatgcaaat gagccccgac agccgctcct attataatga gcttggcggc gaaccgcccc
5340gcgggcaggt aggccctccc aggcgcacct gaactgccgg gtctgggcgg ccccggccgg
5400cccaccttcg cgcctgggcg ggccttcaaa gggtttataa ggctagcacc gtcgccaccg
5460actgtacctc cgccgctgcg cgctttttga cacccgtact gcaacacctg ccgctgccgc
5520cgctgctgcc gccgccggtg cgaggaagga ggagacggcc aagaaagaag ctcgcggaac
5580aagaaagagg cgcggggaaa ggagagagac gcggccgcga ccgccgtcgg gcaacacgca
5640gggggagcga gcgagaaaag gaagagccag cggggacgaa ggagcagaaa gccggccagc
5700cagagagaca gacatccagc cgcggccggc tagctagctc cgaccggccg gccttctgcc
5760aggaccctcg ccgtcgcgct cgccgtaccc ccgtccccgg gtctccggat ctaaaggtga
5820gcagcaagca aaccctttgc cgcgcgcgcc ccgccagccg ccgcggcgag agagccggcg
5880agggcttctc ccgcgccgcg gtaaaacaaa aaaaaaaggg cacgcgcggg ggtgggggga
5940agggagggaa gggaaagaga aggaggggaa ggggaaggag aaggcgccgc actgccgccc
6000gctcccggcc cgccgtccgt cccgtcggag ccgccgccgg tcgcccgagc ttcccctccg
6060cgccgccgcc gccggcggct ttgccgcggc cgccgcagcc ccagctgccc ccccggcgcg
6120cgcgatagcg aggttgctcg ggggggcgct gttgccgccg cggccgcggt cggtgtcgtt
6180cgcagcggcg cgggggccct gccgctgccc gccgcccccc cccctcccct gcgttttgac
6240ggccggccga cccacccgcc cccctacccc gtctccccca ggccaccgca cgcacccacg
6300gccggtcatg tcgtcgcccg gcaggctcga gctggccacg ctcgacctgt acgacctcat
6360cgagtccgcg gacctcggcc cgacgggggg ctcggaggag gacccggccc tgctcgacgc
6420ggcgcgtcgg gctgaggcgc gcgagcgccg gcgggccgcc cgcgccgagc tggccgagct
6480gtggcggatg gtgggcgggg aggacgcgga gagcagcgag gacgacggcg ccggagacgc
6540gggggccacc gagggcgccg aggccgagga cgcggagatc ggcgaggacg ccggcgccgg
6600agacgcgggg ggcgccgagg acgcggacgt cgcggagtgc gccgaggccg agggggcgga
6660gggcgcggag gacgcggaca gcgcctgggc cgcggcgcgc gcgctcgcgg tcgcggtgga
6720ggcagccgcg gccggggcgg aggcggccgc ggccgaagcg gccgtcatag ccgccgccat
6780cgaagccgag gcgggggcgg cgcccctcaa ggccgaagcg gggaccgagg cggggggcgg
6840cggtgccgtc ggggccagga ccgaggccgg cgatgttggg cccgaggact gcagcgatgc
6900cgggtccgag gacagcgggc ccgaggacag cagcgatgcc gggcccgagg acgatggggg
6960cgaggcccgg gaggggagca ccgacgccga cgccgacgcc gacgctgagg ccgaggccgg
7020gactggggcc gggaccagaa ccaaagcggc cccgcgaaag gcgggcgccg ggcccggcgc
7080cccgcggggc cgcgcgcccg ggcccccggc gccctcgccg ccggagacgg cgcccccccc
7140gccgcggcgc cagcgcgggc gcgcaaccgg cgcccgcgct ggctacgccg cggcgccgcg
7200cgacgggccg ccgccgctgg agggcccgct gctgacgcct tctggcgagg cgtggcccgg
7260cagcgcgccg ccgccgcccg gccgcgtgcg cttcggcggc gcgggcgaca ctcgcgaggg
7320cctctgggac tgccccgaga tccgcgaggc ggccgcgcgc tacgcggcgg ccgcgggccc
7380cgcggccgtg ttcgtgccgg agatggggga cgcggggaag cagtacgcgg cgctggtgga
7440cctggtgtac gcgcgccgcg acgccatggc ctggctgcag agcgcgaagc tcgcgggccc
7500ggacctgcag ctggcgcgcc tgctgcagcg gcgcgtgcag ggctgccggg gccacagctc
7560gttcatcacc gggagcgtga cggcgccgct gccgccggtc ggggacgcca tggccgcgca
7620gaacgcgctg tgggcgctgc cgcacgtggc ggcctgcgtg gccatgagcc gccgctacga
7680ctgcgaccag aagctgttcc tcctgcagag cctgcggcgc gcgtacgcgc ccatggccta
7740cccggaggcc ggcgccggcg gcagcggcgc ccgcgccgcg ctcgccgagc tgcgcgccgt
7800gctcgccggc cgcgcggcgc cggcgcccct gccgccggcg agcacggcgc gggcggcgcg
7860cgagcggctg cgcgagctgg cggaccgctg cgccgtcgcc tgccgcgagg cgctggaggc
7920ggcccgccgc gccgccggcg ccgccgggct cccggtgctc tcggccgcgg cgggccgcgg
7980cctgccggcc gcggcctgcg cgccggacgc gctggcggcg cacccggagc gcgtgctccg
8040ggccgccgag ctgctcggcg cggcccgcga cgcggtggag cgcgcgcggc tccagcgcgc
8100ggccccggcg gcgctgcgcg ccgaggcggc tgccgcgctg gaggcggccg cgctggcggc
8160gcggaccgtg gccccgctcg cgcggtactc aacgcgcggc gcggcagccc gcgcgtcggc
8220ctgggcgctg gcgcgcgcgc tgttcagccc gccggcggag gtaccggcgc ggctggcggc
8280cgcgctcgcg gccctggagg ccgccggcgg aggcgctggc gccggcgcgg ccgcgccggg
8340ccgggggccg gtggaagtgg aggtggagga catgagggcc ggggcgccgc gggcggaccc
8400ggaggacggg tccgaggcgg aggatgagga ggctgaggag gacggggagg acgaagaggc
8460ggaagaggag gaagaggagg aaggggacgg ggaggacgaa gaggcggaag aggaggaaga
8520ggaggaaaag ggccgccccg gcccggcggc gctcccgccg ccgggtccga gggaaggaag
8580aagggccgag gaggaggagg aggaggagga ggaggaagaa ggggacgggg acggggacgg
8640cgaggcggcg gccctgccgg ccgccgcggg gggcccctcg ggggaggacg actctgggcc
8700gaggcgccgg cgaaaagccg ccgccgccga cgcggccggg ccggcgcggc gggagccgcc
8760gctgcccgcc cgcgtgctgg ggcccatgcc gcccggcggc cccgccgccg acggcggctt
8820ccgccgcgtg ccgcccgggg actaccacac gcccgcgccc agcgccgcgg cgctggcggc
8880ctactgccgc cccgaggtcg cggcgcggct cgcggaccac ccgctcttcc ccgagccctg
8940gcgcccggcg ctcgccttcg accccgaggc gctggccgag atcgcggccc gccgccgcgc
9000gggccccgcg ggcgcgctcg ccgccagcgc gccgctgcgg cggcgcgtgg cctggatgtc
9060gcagatcgcg gaccccgagg acgtgcgcgt ggtggtgctc tacgacccgc tgcccgggga
9120ggcgctggcg gcgccgcccg gcgaggacga gcgccggcgg cccgagtggc cgccgcgccg
9180cggcgggctc tcgcacgcgc tcgcggcgct gggcaaccgg ctgctgctga gcgccgactc
9240gcacgcctgg gccgggcgct ggacgggcgc gccggacgtg agcgcgctcg gcgcgcaggg
9300cgtgctgctg ctctcgacgc gggacctggc cttccgcggc gcggtggagt acctctgcgc
9360gcggctggcc gcggcgcggc ggcggctgat cgtgctcgac gccgtggacc ccgagaactg
9420gccgcgcgac ggcccggccg tcgggcaggc gcacgtgtac ctgcgcgccg cggtgctgcc
9480cgcggcgcag tgcgccgcgc gctggcccga gcggcgcgcg ctggcgcgcg ccgtgctggc
9540ctcgcggcgc gtcttcggcc cgggcgcctt cgcgcgcgcc gaggccgcct acgcgcggct
9600ctaccccgag gcgccgccgc tgcggctctg ccgcggcggc aacgtgcgct acacggtggc
9660cacgcgcctg ggcccgcgca ccgcggtgcc cgtgccgccg cgcgagtacc ggcagcgcgt
9720gctgccggcg ctcgacgggc gcaaggacat ggccgcgcag ggcgcggcgc tggggctcgg
9780ggagccggac ttcgtggagg gcgaggcggc cagccaccgc gccgccaacc gctgggggct
9840cggcgcgccg ctgcggccgg tgtacctggc ctgcgggcgg cgcgcgctgg agctggcgcc
9900cgacgagctg ccggccgcgg cggtggcctt ctgcgcggcc gcgctgccgg agccgcgcgc
9960cgaggcgccg ccgctggtgc tggaggccgc ggcggcgccg cccgcggccg cggcgcccgg
10020cgtggactgg gacgcggacc agggcccgcg ggagacgctc gtgctgctgc ggcgcgccgc
10080gggcggcggc ctggtggagc gcgtgccgcc gccggcggcg gaagccccgc cggcccgggt
10140gccggcgcag tcgtccccgg gcgcgggctc gggcttcccg gcgccggcgg gcggcggccg
10200gcggccgcgg cggccccggc acgggccgcc gccgcgcgtg gaggtgctct cctcctcctc
10260ctccgcctcc tcgtccgcgg cgtcgtcccc cgcctcgtcg gacgacgacg aggccggcgc
10320cgccggcggc gggccggcct cgccctaggg gggcccgcgg gaagggaggg agggggcgcg
10380acggcggcaa taaagacgag tctgtgcgaa cacacgcggt ccgagtgcgg ctctttcttc
10440attgtcgggc ctcgggggcg gggggaggcg cgggccgcgc gccgctgcgg agcggccgcg
10500gagggccagg acccggcgcc ggagacgcgg cgctggcgtc cgccgccacg ttccccgcgt
10560cgggcacttg ccctccgcgg acaagggggt tggcgcgcgg ccgccccgcc gccgccgctg
10620ctgccgccgc cgccgccgcc gccgccgctg ctgccgccgc cgccgccgcc cgcccgcccc
10680aggccctcgg tctcggtcgg agcgcggtcc ggcgcgcggc gcgcggggca ggccccgggg
10740cgcgaagccc gggagggacg cgggcgtgga gcgcgaagct ccggcggggc gcggggacag
10800cgcccgcgcg gggctcgccg gcccccgggc tcgggcccct gggcgccggg ggtcggggcg
10860cgaggcccgg gctcgggccc ccgggcgccg ggggcggggg cgggggcggg ggccccgggg
10920gccaagacgc agaaccccgg ccccccggcc ggggcccgag gcccgcgggc ggggccgggg
10980cgcggggcgc cggacccagg ggcggagccc agagcgggtc cgggcccgcc gcgccgaaat
11040ttccgccccc ccccaaaaac acccccccgg ggttgcaagg ggcccgcgcg gcgcggcgcg
11100gaggg
111054102478DNABovine herpesvirus 1misc_featureUnique Region - Long
4gcccagcccc cgcgcggggg gcgcagagaa aaaaaaaatt tttttcgcgc ggcgcgtgca
60ttgcggcggg cgggggcggg gtgggggatg ggcgcggagc gcgagggtag ggttggcaca
120cggccaagat caccgagcat gtgcgcggcc atcttgcttc caaactcatt agcatacccc
180gcccagtatt ccattctcat ttgcataccc accgtcgcac atgccgccat attgctcctc
240ctccctcgct cctcctccct cgctcctcct ccctcgctcc tcctccctcg ctcctcctcc
300ctcgctcctc ctccctcgct cctcctccct cgctcctcct ccctcgctcc tcctccctcg
360ctcctcctcc ctcgctcctc ctccctcgct cctcctccct cgctcctcct ccctcgctcc
420tcctccctcg ctcctcctca aaacactacc gcgggcgtcc gctcccacta gcttcggcgc
480cgtcatgggt gcccgtgcct ccgcgcctgc tgccggtccg cccccagccc acgctgttct
540actagatgcg ctctccgggc gcacgatcga cctgcccggc ggcgacgagg ccgtctttgt
600gtcctgcccg acgacgcgcc ccgtgcacca ccacatgcgc cgcggccgca cggcccacac
660tacacccgtg cacttcgttg gccgcgccta tgccatcttg ccctgccgca agtttatgct
720gtatctgatg cgcggtggtg ccgtttacgg ctacgagccc accactggcc tgcaccgcct
780cgccgattca ctgcacgact ttcttactac tgccggacta cagcagcgag acctacactg
840cctcgatgtc acggtgcttg acgcgcagat ggacccggtg acgttcacca cccctgagat
900cctcatcgag ctcgaggcgg acccggcctt cccaccgcca ccctcggccc gcgcgcgccg
960ctccacgctg cgccgggcgt ctatgcgccg gcccgcacgc accttctgcc cccaccagct
1020agcagagggc tccattctgg acctctgctc gccagagcaa gcggcggcgc cgggctgttc
1080gctgctcccc gcctgtgact ctggagacgc cgcgtgcccc tgcgacgctg gcgagaccgc
1140ccgtgactgt actgccgatg ccgcgcccgc tcccagcccc ggcgccttat ctcgctatag
1200ctccgtgcgc tcggtgttct tttagcgcgc gggcgcccgt gtgggacata cattaataaa
1260tgcagcgttt cttactctac tgtagtggct ggccgtttgc ttctttttgg gattggcaat
1320ttagcgttcc gtcgacgcca catcttttgc ctctctgttt cccgttgcgt gcgcgcgtgt
1380cgccgagccg acttgccccg acaacacagg caggcacgcg gccccgcgcc ccgccaggca
1440ctatttgcgc tcgggtgcat tgagcttgac tttgactcgc ttttgtgccg acgcccaatt
1500atttgccttg gcccgttgtg tcccccccgc gcgcgcttgt gccgcccaag tccgcccgcc
1560cgatagcgcg cccgcgcctg tgtccccaac aagtactata cacactcgag tatatcgggt
1620tcaaatcaat gttgacttta ttagcttaga agatctcgtt gcagtaaaag tattttccgt
1680gcatgtacac gggaaccagg gtgaaattag cgacgagctt gcacgtcatg ctgtcgcagg
1740cctgtttgtg tgtgtccagg gcatcgatga gccccgccac gcaggccccg gggatgtact
1800cctcaaaagg cgcgtcgccc acagtcacct ccaacagcgg cacgcactct gcgccggagc
1860gcaccgcgcg gcttagacgc gccaacatca cgaacatgta cgatgcgggg caggtggcga
1920ggcttagccg gcgcgcagcg cagagctcct ccagcgaggg tagcccgcgc ccgcgcaggt
1980agcagcgcag aaaaggcgct agcttcagcc gcaggttttc cagcacggcg ccggccgtgg
2040ccacgatagg gtctttggtg cgcaggcgca agttcttggt ggcgatgaac ttgcaccacg
2100ttaggcactc gtcggccgag gccagtgcgt ctaccaggtt ttcgttgcgc agcaccaggt
2160ctcgcagcgc ccgcgccgcc tgggcggcgt gcgagcgcac ctcaaacatg cggtagaggt
2220cgcggccgtg gaacatgagc gtctcccagg tgacgcggcg gccctcggga acgaattgct
2280ccgcgccaaa gtccaagacg gctgcccatg gcgacacgcc cgctgcgcgg aacccgccgt
2340tttgcacggg ccgcatgagg tccagtcgcg cgcccgcgaa gacggcggtg acgcgctcgg
2400ccgtggctcg ctgcgccgct tcggccaagc ttcgcgcgag ccgcagcgag ctcccgatcg
2460agcgggcggc ggcgcccccg ccgccgtgtg aagacgtcgc gagggccgcc tcgcgctttg
2520ctgccgggcc gcgggaccgc tgctctccgg cgggctgcct tcggcgcggg cgcctgcgcg
2580gccgccgcgg ccgcacgcga gcccgccgcg ccggaggtgc ttcggcggga ccgccgtcgc
2640cgcttgcggc gccttcgccc ggcggctcgg ccggcatcgg ctcgtcctcc gcgccctcca
2700gcttgcgctt gcgaacctgc cccaccacgg agcgcagggc gggagcgagc gagggcgcct
2760cgtcgtcttc ttcgcggtca gagccgaaga ggctcaagtc gtcgctctcg ctggccgtgc
2820tgagggttgc gatctcgggg tccgccatgc cgctgcgact cgcgggcgtc gtcgtcgggc
2880cgggtgcgtc gccgttcggg ccggacggtg tctcgcgttt ctaaaagagg gctcgcactc
2940cggcgccgtg ttcgcactga gaccggcatt ttatgttcgc tggccccacc ctgcgcggca
3000gcagcgccgc ccaatagggg cggtcacgtc tgcgcgccca gcagccgcag gcgcaggttg
3060tgctcgtagt gcagcagcgc gatgacgccc cccacgatag cggccaggta gagcgccttt
3120acgagcagcc ccgcgagcag cgtggagcag cagttcacgc acacctttct gatcccgctc
3180tcgccgccat cgccgccatc gccggcgacg gcgctgcccc cgcgccgccg cgcgggcttg
3240cggtatagca gcgagaccag ttccaatccg gcaaagaggg cgacgtgaac ccacgcccag
3300attttcaggt acagcgggta ggcggccgcg cagggcgcgt gcgttatgcc gacgctgctg
3360gccgccgcaa tccgcgcgcc gagccgcgcc aagccctccg caagcagcgg gagcagcagc
3420cccgggcggc gccaagcgca gcccaggggg tcgaggcgga agttgacagc aagcgcgcgc
3480cggcgcgccg agagctcgca catgagccgc gcgagcttcg tgtacgggcc gtggccgact
3540acggccgcga gcgcggcggc agcgtagttg agggtgtagc cgccggggct gaggaagtcg
3600gcgtcgttgc ggcaaatgcc gaacatgcgc cgctcctggc gcaggtacac gaacgcgacg
3660tacagcagcc atgccagcag cgcgctgcga gcctgcgcgg accacaggta ggcgcggcaa
3720tcgcgcgcgc cggccacggc gcgcacgcgg ccgtgcagcg cttcgtcgcc gtcgagcagc
3780ccgggcggga tgtgctgcac gacggcgtgc cggcacgggg cgtcggccgc gagcgtggcg
3840ttgttcgcgc cgccccagac gtagacggcg ccggggtcgc gcagctccca gcggagcgag
3900ccgttggcgc cggtggcgcg gacggcgagc gcacagcgct cgcgcagcgg cgcggcgagc
3960gcggcccaca gcgccagcgc gaggtgggcc gtgagcagcg ccagcgcggc caagttaaca
4020gtccgccccc cgagcagcat accgcgccgc gcgccccgag agatccacgg tgaacacggt
4080accgaggcgg ttgctgccgc acttggtagc gaagcactgc tggatgagcg aggcacacag
4140gcggtcgtgc gagtcgacac tgagggacac cagcgagcgg gccttgtttt gggccgcgcg
4200cccgtgggcc gcgcgcaggc agccaaagcc ctgcgcggtg ccggcgcgcg cgcgcgccgg
4260cacgagctgc gccagcagcc agtcggcttt ggcggccacg aggcgcgcgc cggcgccttg
4320gtactcgcgc gccgcctgcg ggtagtgctc cgccatgtag ggcgccagct cggcctcgat
4380tacgtcagca ataaactctt cgacggcgcc acggtcgccg ccgtcgacgc cgacggcggc
4440gagcgcgcgc cgcagggaaa cgcgcacgcc gtgaaaggcc gcgcggttga cggcggcctt
4500gcgctcaaaa aagctaacgt attcgccgcc aacgctgcgc agcacgtgcg tgcgcggcgg
4560cgcgcccgcg ggtggcgcgg cgtggaagtg gaagtggtgc gggtcgcggt gcgcggcgac
4620gaaggcggcc acgtcgtcgc agcgctctgg gaccacgtag aagggcagga gccaccgccc
4680gacgttgctt gcggcgtctg gcttgccaaa aaagggcaaa cgcaggctgt gcccgtgcgt
4740gtagacagcc gcgtcaacga aggcaaagtc gcgcaagtag cggctcatgg cctcggcgaa
4800ggggcgttcc agcatgacgg catgctggac gaggcgcgcg atgcccttga gcgtggggcc
4860gccggcgata atgtatggcg ccgggacggg cacagccacg cggaagccca ttttgtcgtc
4920gcatccgcac gcggtcgtta gggccgccgc gcttcccgcg ccctccgcgc cgcccgtctc
4980ttcaggccgg gcgcccgcgg ggtcgctgac gtcctcgcag ctgtattgcg cctcgccctc
5040gcgcgcgagg gcgctctcgt actcgtccca gcccgcgtcg cggtcgggcg cggcccagga
5100cggcgacgcg tcgccgtcgc ctaggttgct agcggcggcc gaagggcacg cgctcttgta
5160gaagaagcag gggtgtgcgg gccaggcatc ggcggcgatt tcggggaaca gcgccgcgag
5220cgcggcaagc gcgccgcgac ggaagctgcg catggctccg tgcaggtctc cgcgggggag
5280ggggcgcttg aggcgaaagt ccacgtccag gacgatgttg gttacggcga ggcgggcgtt
5340gaacagctcg ttgcggttca cgtagtactg gtcgcgcggc gcggccgggc ccaggctccg
5400gcggtccgag cggccggcgg cacaggccgc gcgctcagtg aggagcgcgg ttagccgcgc
5460gtctcgctcc acaagcgcgt cccggccgct ctctgcggcg gcggcagcgg ccgccgcaac
5520ctcgaccgcc acttcgtcgg ggtctagggc ggcgacgctc gtgacggcgg cccagtcgtc
5580gccgtccgcg acggcaaatg cctggtggcc gcgcggtagc tccactcggt agacgggcgt
5640gggcgccgcg gtcccgcgcg cgccaaagag cccgtccagc ggatgcgcgc cgtcgcgcgc
5700ggcggcggcc gccagctcaa gtagccgctt ggacaccccg cagcaggcgg gcgtcgcatc
5760aggggacgca ccgccgtccg gcgcgccaag cgcaagcgcg gcgtctagcc ccgggcccgg
5820caccgcgctt gcgcttggcg cgccgggtgc gtgcagcacc cacccgaagc gagccgcctg
5880gccctcgagg tggtccagcg ctgcgcgcag ggcggccgcg ccgtcgcaga ttgtgcgccc
5940gggcccatta gcggtcgccg cgagcaagcg cgcgtacgta cgcgcgcgcg cgtaagcctc
6000ggctgttgcg gggggcagcc gaacaacggc gaccgccacg ttctgttcga tgtagctttg
6060gacgttaaac tgcgcgcgca cgtgccgaaa aaaagcgtca acggcgcgct cgcggaggcg
6120cgagacgccc gcgaggcgcg gcgcgagcgc ctcgccgcca tcggggggct cggtggcggt
6180gacggcgcgc aggtgctcgg tgatctgccg gcgattaaag ccctcaaagt aggccaagta
6240tacgtaggcc acgaactccg ggtcggccac tttaagactg cgacggtcgt ggtcgatgta
6300ctcgcgcagg cagcggacct cggcgaggtc ggcctcgatg cgcgcggcca cgtacgcggg
6360tgccccggcg gcaaccgcgc cgcgggcgta gccgctgcgg cagcagaagg cggcaagcgc
6420cgcgaaggaa accaagtcgg ggaaggcgag tcccgagggg ttaggcggcg cggcgacggc
6480gtacgtggcc aggcagtccc gcacggcctg caggtcgtag gtagcggcgt cgccggcgcg
6540ctcagcctgg aacacgtaga agcgcgtggc caacaccaag gttttttcgc cgggcccaaa
6600cttggagagg aaccagaagg gagtcgcacc gctgttggcg taaagccgcc ggtaggcggc
6660gaccgttttg tgctcgtggt ggatgtagag cgaggctagg ccgcggcggc cggccgggcg
6720cgcgcgcagg gccgagcgca ctgtagtctg gccctcaaca tagcgggcgt cgtctgcggt
6780gcggccggtg cgaggcgcca gctgctccgt ggccaccagc agcgcggtga tcatgtccgc
6840gtgcagcgca aaggtgacgt cctcggcgag gtgctcgagc agcacgcgcg cgggtagggc
6900cttgccgagg agcagtgcgt cggcgagcgc gcgcgcgccc tgcgcgctgt tgaaggtgca
6960cacgaagacg ggccaggcgc ggggtcgcgc ggcggcgctt ccgcccggcg ggccgcccag
7020cagataaaac gcgacgagcg gccgcgcatc cgccagcgcc agcgccacgt cgtttgggct
7080ttcgccacca aggcacgcgg cgagccgccc gggccagttg taggagacca cgtaggcgcc
7140acggccgggc tcctcctggc ccgtgagcag catcagcgaa aacccgatcg cgcagccgtc
7200ggtggcgtac aggatttgga gcgcgtcctc gagcgcggct gggccgtcca tggcgctgca
7260gcggctggtc gggtggctgt gcgggcgcgg cgggggcacg cgagacgctc cgcagtacga
7320gccgctggcg cggcgcctga gcggaccgac gctatttcgc ctgcaagaag cggtggtagc
7380cgtcagcgcg ctgctgccgg cgccgctgac agtggaggac gtggcgcgct cggcagacgg
7440cacgcggcgg cttgccaagg cgcagtcgct agcgcggacc tactacatct gccagcggaa
7500catcgagtgc ctctcaaagc accaggccgc gtgtagtgac gcaagcatca ccgccgtcgt
7560gacgaagcac atacaggatg ctcagcgcat gcgcgacacc tgcctggccg ccttgcttca
7620aatgtaccac tcggtgggcg ctgtggaggg cacgacggac agcatggtgg accaggccat
7680ccgcatggcg gccgaaagca acattgtaat ggccgatgtt gcggtgctgg agcgcgcctt
7740gggcattcag gcgcagggcg cgggcgcgga ggcggcggcc agggcaagcc cgacggccgt
7800tggtgccgag gctcgggccc cgccgcccct gccgcggcag ccggccgcct cggcgccggt
7860cgccgtgtct ccggcaccgc cggtggcgcc tgcagaggcg gccgccacaa aaccacctag
7920ccgcgcgggg cgcgcggcgg ccgccgcttc ttcccccgcc gttttgcagc ttgcggcgta
7980gcccggtgca ataaaagcaa aataagtata cgcaaaacac gtgtgtggtg gagtcggtgt
8040actttaatgt gctttgtttt acagcccggt ggacccaaag ccgcgcggcc cgcgcgcaga
8100ggggggcacc gccgcggcga gatcggcgac gcggcgccag cgcaggcgcg gggccccagg
8160ggcgggcggt gctgcgcgag ggctagttgg gaagggctcg cggtcgttga ggccggacgg
8220aagccactcg aggcgccgtg ccagcagaag cagctgcgcc acgcgctggc ctgcggcagc
8280aacgagcggt tcctgcgtga cgtttcgcaa gacaaagcgg cagggctccc cggggggcca
8340ggctgtcggc aggacgatca gcccccgaag gttgcaggac gatcgaccaa acacgtaggg
8400cgcggcagcg tgggcgtctg ccgcgtaggc tacgggcagc cgcacgtgta aattttcccc
8460gggtgccaag acggccgtgt atggcatggc aatatcgtac ccggcgtcct cgtcgcgttt
8520gggggcgaac gtggcaaaga agggcacttc gacgcccgcc tctgtcccgg cgtttgcgtc
8580gtcgtcgacg gcgatgaggc gaggcagcgt ggtggttagc cgcgcgagcg tcagccgcag
8640cgcaagcccc gccgggggag cggccgctgc ggactcgggc gcccagacga tggcgcgcaa
8700gatccccgag tagcccgagt cgacgatgcc gacggccacg gctggtgggc ggggcatgtg
8760tgtgtcaccc gagcgcattt gcgacattat aatggcatat ccgccgggcg cggccgcctt
8820catgtttaaa ttaatcagcc ggctataaag gagagatccc gacggggctg tttcatctcg
8880ctttgctgct ggcgcaattg ggccccagag cgccagcgag tcgggctcac agcagctttc
8940caaccgccag ggggccgcct ccgcgttgag ctctacgacg aggatgccgc ggtcgccgct
9000catcgttgcg gttgtggccg ccgcgctgtt tgccatcgtg cgcggccgcg accccctgct
9060agacgcgatg cggcgcgagg gggcaatgga cttttggagc gcaggctgct acgcgcgcgg
9120ggtgccgctc tcggagccac cgcaggccct ggttgttttt tacgtggccc tgaccgcggt
9180aatggtcgcc gtggccctgt acgcgtacgg gctttgcttt aggctcatgg gcgccagcgg
9240gcccaataaa aaggagtcgc gggggcgggg ctgattgacc gcaacgctgc ggagtaactt
9300gtatataaag ctcgcggtcc cggcgaccgc tgcctttttc gcactcggcc cgacccgctt
9360tgagctgcac gcccgccggc ccgccgactc gcttgccatg gcccggttcc acaggccctc
9420cgaagacgag gacgattacg agtacagcga cctttgggtg cgagaaaaca gcctctatga
9480ctacgagtcc ggctcggatg accacgtata cgaagagctg cgcgccgcga cgagcggacc
9540cgagccgagc gggcggcgcg ctagcgtccg tgcgtgcgcc agcgctgcag ccgtccagcc
9600cgccgcccgc ggccgcgatc gagccgcagc cgcggggacg accgtagctg cgcccgccgc
9660cgcgccggcc cgccgctcga gcagccgggc gtcctcgcgc ccgccgcgag ctgccgccga
9720cccgcccgtc ctccggccag ccacgcgcgg gtcctccggc ggcgccgggg cagtcgccgt
9780cggtccacct cgacctcgcg cgccccccgg tgctaatgct gttgcgtctg gccggccgct
9840ggcgttcagc gcggctccga aaacgcccaa ggcgccctgg tgtggaccga cgcacgccta
9900caaccgaacg atcttttgcg aggccgtcgc gctcgtggcc gccgagtacg cccggcaggc
9960ggctgccagc gtctgggact cggacccccc aaagagcaac gagcgattgg atcgcatgtt
10020gaagtcggcg gcaattcgca tcctcgtgtg cgagggctcc gggcttctcg ccgccgcgaa
10080cgacatcttg gccgcgcggg cccagcgccc cgccgcgcgc gggagcacaa gcggcgggga
10140aagccgcctt cgcggcgagc gggcccggcc gtagcgcgag cgggagggct ttttcgacgc
10200gcgcggctta agcagcgcgc tgctgtgcta gtatgaaaat aaacgcttgt taattaaaca
10260caccaagccg agttgcgttg tctttgggat gagcgggcgc ataaaaaccg cgggccgcgc
10320gctcgccagt cagtgcggcg gtgctgcggc ggcaaccatg gacccgtacg acgccattga
10380agcgttcgat gactccctgc tcgggtcgcc gctcgcggcg gggccgcttt atgacggccc
10440gtcccccgcg cggttcgcgc tgccgccccc gcgcccggct cccctggccg cgttgctgga
10500gcgaatgcag gccgagctgg gcttccccga cggccccgcg ctgctgcggg ccatggagcg
10560gtggaacgag gacttattct cgtgtctgcc gaccaacgca gacctgtacg cagacgccgc
10620gctgctctcg gcagacgcag acgcggtagt gggcgccatg tacctagcgg tgcctgggga
10680cgcggagcgc ttggacttga acgcgcacgc gaaccagccg cttcccgcac cgccggcctc
10740ggaggagggc ctcccggagt atgtggccgg cgtacaggcg cattttctgg cagagctgcg
10800cgcgcgggaa gagcggtacg cgggcctgtt tttgggctac tgccgcgcgc tgctgcagca
10860cctgcgcgcg acggcggcgc gtggccgagg cgcggcgggc gcgggcgccc aggcagaccg
10920cctgcggcag ctggtggcgg cgcggtacta ccgcgaggcg agcgcgctgg cgcggctggc
10980ctttgcgcat atgtacgtgg cgacggcgcg cgaagtctct tggcgcctgc actcccagca
11040gagccaggcg cagggcgtgt tcgtttcgct gtactatgct tggccgcagc ggcggcagtt
11100cacctgcctg ttccaccccg tgctgttcaa ccacggcgtc gtggcgctgg aggacggctt
11160cttggacgcg gcggagctgc ggcggctaaa ctaccggcgt cgggagctgg ggctgccgct
11220ggtccgcgcg gggctggtcg aggttgaagt ggggcctctg gtggaggagc cgccgttttc
11280gggaagcttg ccgcgggcgc tgggcttcct gaattaccaa gtacgcgcga agatgggcgc
11340gcccgccgag gccggcgggc ggctggcgcc ggagcgggag cactcgtacg cgcggccgcg
11400cggcgcgatc aactacggga cgactccaga ggccatgttg cggcccccgt cgccgagcga
11460agtgctgccg tgcgaccccg cgccagcggc taccgtgcgc gtggcgagcc ccgccacaca
11520tctggctcag gcgccttcag ccaagggcgc cgccccggcc gagtttgccg ccttggctgg
11580gcttgcaagg cccggtccgg ccccgctcgc ggcggccccg gcccaagccc cgttcgcagc
11640ggccttggcc ttagccgagc ccgcggcagc cctggccccg gccccgcttg cggcggcccc
11700agccgagccc gcggcggccg tcgccgggcc aagcccggca aacccattcg gcggcacgta
11760tgacgcgctg ctgggggacc gcctcaacca gctgctggac ttctaagggc gggcgggcag
11820tggcgctttc gacccggcgc gtggcgtttg cgaggcctcc ctctggcgta aggcctctgg
11880cgccgccctg cgggcggcgc gagcgtataa aagccacttg ggtctacacg ggatttagtt
11940ttcgcgcccg cggctttcta ggcgccctta gacgccatgg acgccgctag ggatgggcgg
12000cctgagcgcc gcccgcgccg ctccggaacg taccgcacgc acccgttcca gcgcccctct
12060gcccggcgga gcctgctgga cgccctgcgc gctgcggacg ccgaggccgc ggagcgcccg
12120cgggtccggc gcccgcggcc tgacttccag cggcccccgg acgaggacac cagtgaggac
12180gagaacgtgt atgattacat cgacggcgat agcagcgaca gcgccgacga ctatgatagc
12240gattatttta ctgctaaccg cggccccaat cacggcgccg gcgatgctat ggacacagac
12300gcaccacccg agcgcgcccc ggaagggggt gccccgcaag actacttgac ggcccacctg
12360cgcgccatcg aggccctgcc cgagtcagcg ccccaccgga gcctgctgga gcgcacggcc
12420cggaccgtgt atgcgcagca gtttcccccg cgcgatttga gtgcgggctc cagggcgccg
12480gcacagcgcg cgcggcggag cctccgcggc ttcccgcgtg gcggcggggg cggccaggaa
12540cccgggccag acgacgaagg cgacgacgcc gcagacctgc gcgaggacct tgtgccagat
12600gaggcctacg cgcacctaga gcgcgacgag cggctgtcgg aagggccccc gctcctcaac
12660atggaggcgg ccgctgcggc tgcgggggag aggagcgtgg tggaggagct gtttacgtac
12720gcccctgccc agcctcaggt agaggtgccg ctgcccagga ttttggaggg ccgggtgcgg
12780cccagcgcct tcttcgcgca gatgccgctg gacgcgctgt gccgcacgcc gcccaacgat
12840cagcgcgtgg tgcgcgagcg gcgcgcttgg gagatggccg gtacgccgca tgggctccta
12900ataaccacgt ggagcacggt ggacccggaa ttctcgatcg gcggcatgta cgtgggcgcc
12960cctgagggca cccggccccg gctagtgtgg cggcgcgcga tgaagcaggc catggcgctg
13020cagtaccggc tgggggtggg gggcctgtgc cgagcagtag acggcgcagc aatgccgccc
13080actgaggcgc tgctcttttt ggcggacgcg ctgctgcgcg tagtgcgcaa ctgccatttt
13140ttgtcgcggc cggggcgcgc gggcggcgcc gcgcggcgcc tgcccgcggc ggcggttggg
13200ctgctggcag ccacgcagtt cacgccaccg gacgcgtccc cccacgcgac gctctttcgc
13260ggctcaatgg gctccctgat ttactggcac gagctgcgcg tgatgctgac tgcggtgccg
13320gccctgtgcg cgcgctacgc gggcgccggg ctgcagtcgg ccgagctgta cctgctggcg
13380ctagcgcact cagaggcgcc cggctacacg gcaaatgagc gctacgcgct ctcggcgtac
13440ctgacgctgt ttgtagcgct cgcggagcgg gcgctgcgct ggctgtatct agcgggcgcg
13500cacctgctcg ggccgcaccc cacagcggcg gccttccgcg aagtgcgcgc caagatcccg
13560tacgagcggc tgccgctagg cagcgcgacg ctgcacgacg ccgaagtgga gacggtggac
13620tcggccacct tccaggaggc cctggctttt agcgcgctgg cacatgttta cggggaggcc
13680tacgtagcgg tgcggaccgc gacgacgctg ctgatggccg agtacgcggc ccacgctgag
13740cgccgggacg tgcgcgagat gacagcggcc ttcctgggcg tggggctgat cgcgcagcgg
13800ctgatgggca gcctgaacct gctgctgaac tgcgtagccg gcgcagcggt gtacgggggc
13860cggcgtgtga cggtgcgcga gggcacgctc gcgcggtaca gcctgctagc ggacgcggca
13920ctgccgctgg tgcgcccggt gtccctggtg gagttctggg aggcccgcga cggcgtcatg
13980cgcgagctgc ggctgcggcc cgtggcgagc ccgcccctgg ccggcaagcg gcgggtcatg
14040gagctgtacc tctcgctgga cagcatagag gcgctggtcg gccgcgagcc gctaggttcg
14100cggccggtgc ttgggccgct cgtggacatc gcggaggcgc tggcggacca cccgcacctc
14160gtcacgggcg atgggcgggg cccgcgcctg ggcggccgct aggcggcagg ccgcgcttac
14220gcggcggctg ggtccgccca catcagccac cacgcccgcg cgcccgcccc gccctcgtat
14280gcctatatag ccatcacgct tgaatgccaa gcgccacttt cccgccgcgg cgaaatggcg
14340tggccggccg cctctcgggg cctcatcgag cggcgggcag agaaggggtg cctgctgccg
14400acgctcgcag atgccacggc cgcggccgtg gtggccttgc aggaggcgac cgagcctctg
14460tgcggggctc cgctgtttgg cgccgagcgc gcggccgcgc tgctcggcgt gcgctccaac
14520gccgtcccgg aggcgctggt tctgtcggac tcggcgaaag acgccgacga cgagtaccgg
14580ctggagtatg accgcgccgc agcgcgggtg ctggcgggcg cgcggctctc taaggacgcc
14640gtctggcgcg cggtcatcgg ctcgtactgg aagtacctga aggcctcgag cggcgctgac
14700gtgaacatcg acggcgcggc cggcggcgcg gcgatggagc aggcgcagct gacgaacgtg
14760atgctctttg cgcccacata cgcgcgccgg gcctcgcgct cgccgttcaa gcacaagcag
14820gacaacgcgg cgtacaaaac cgcagcggcg gagctgcgcg gcgccctgcg cgcggtggaa
14880aagtatatgt attacatgcg gccgggcgac cccatggtcg aaagccccga cacggaagcc
14940cgcctgcagg aaattttggc gtacgccgcg acggcctacc gctggctgct gtggttcatg
15000gacgcgctcg atggcacggt gctgcgcaag cttggcaagc gcccctcggc cgcggtgggg
15060ccgcgcgagc cgcagccgcc gggcgagctg tgcgagcgcc atctgaccgg cggcccgggg
15120atcgcctgcg gcagcggggc cgcgctcatg ctgacggccc tgacggcggc ggtgctggcc
15180ttgctactgc gcgtcggggc cgcttggacg gaatcgtcat ggaagagcaa tacgcagggc
15240gtgacgggag ccatcgtcgc cgcggtcgag ctggcgtcgg ccgtacacca ccacctgcag
15300tacctgctca acatggcctt tgtggggtac gcctgctggc tgcgcgcggg cgtgcgcgac
15360ccgtacatga tcgcggccat ccgcgcgcag tgccgcttcg ctcactttac ggggcagctg
15420atgccgacca tgacttccgc cagctgggcg gccctggagc gcggcacggc gagctggttt
15480aagctggcgc tgctgaaaag cgtggcggcg cacggcgcgc agacgcgcta ctactccaac
15540atcgtggagt cgatgcggct cggcgggagc cgcgggctgc tggcgccggt gcgcgcgcgg
15600ccgtcgggcc gcggccgccg ctgcccgcag agtctggccg cgcgcccctt gcccagcctg
15660ccggccgcgg ccgccgcccc tccgggctcg ggctcgggct cgggctcggg ctctgactct
15720gactccgacc tggatctcgg ctttgccccc gccgtcggcg tctatgcctc gatgcgcaac
15780ctggagggcg cctatgccga cgcgggcggc ccgctttcgc cggcggcaag cgccgcgcgg
15840cgggaggcgg cggtgtacga aaacgaaggc gagggcgaat tcgcgccttt gccctcggcg
15900ttcgccgaag acggcagctc cgacagcgcc gacgagctcg ctatcgacgg ccccatgcct
15960gccccgccgc cccgcggtgg ccgcggcgcc gacgagctcg ccatcgacgg tcccatgcct
16020gccccgccgc cccgcggcgg ccgcggcgcc gacgagctcg ccatcgacgg ccccatgcct
16080gccccgccgc cccgcggcgg ccgcggcgcc tctgctgggc gcctccagta cgctgatttg
16140tgcgccgtct cgagtgacga cgacgaggac gagggcaagg acgaggacga gaacaaggcc
16200ggggcgaccg ccccgttggc cgcggacccc gaatcggaac tggcccgcgc catgcggcgt
16260tgcagcctcc gcgtcccggc ctcggccccg gccccggccc cggccccgtg caccgagcgc
16320ccgggtaatc caacccggtc ttactcgcgc tcgcgccctc ggctccgcgc cctagacgac
16380cggcacggcc tggaggcgct ggcggctgcc ggtgccgctc acaccgcgcg ccacaaccgc
16440gacgtgtggc agcgcttttc ccgcgtctgc gaggccggcg acgactacga aaactacgac
16500gaggcccgcg gcgcagagcg cggacacctc tcttgcgcct cccgcgcgcg gcctgaggtg
16560gagagggtaa cgtcgctgta aaggcgccca ccgcaaacgc tgtaacacac acacaataaa
16620aagtttgttt tagtttatta tgaaattgta catgcgtggt ctttgggggg ggggcgcggc
16680ggctttgccg tcggggcccc gcgcctacag gcgcgcccgg gccttgcgcc gcaggcacga
16740ggccgccacc agcaggagcc ccacggcgcc gagaccgcag gcgacggcca cgacgctgac
16800gaggacgggg cttccgatta ggccgggcga ggcgtcgtac gtggcggtcg cggagaactc
16860gggcagcggt gccgggtagc cagtggcggt gcaggtgtag tcgacgggcc cgtcggttgt
16920agaaagcagg cgcacgccgc gcaggtttac cagcccgggc cgctcggcgc agacgccggt
16980ctgctcagtg cgcgacgggg cgatgccgtc gcgcaccgtc cagcgcaggg agacgcgccc
17040ctcggggacg cagcgcgcct cgcagacggc ctcgccgccc tcgaagtaca cgcgcagctc
17100gggcgggcgg taaacggccg gcgtgccagc cgcgtaaaag cggcgctcca tgttagcgct
17160ctggaaccag gagacgtcgc agcgcaggtt gggcgggtgg gcggttggcg tcgcgtcctc
17220gagcgtaagg acggacgtgc gcgaaaagag cccggagtcg tcgaccgtaa agacgtcgcg
17280cgcgtgccga gcctccacgg ggtagccgtt gcggaaccag tgcaggcgcg tggagcgcgg
17340cgggtagtac tcggcggcgc ggcacacggc cgcgtagccg gcgccttcta gcgctggctg
17400gggttcgacg gaaacagcgg gcgcgcggtg cgtcgtgacg gtcacgacct tgcgctgtga
17460cttggtgccc atgtcgcggc gccaagtgta cacgccctcg gtggcggccg tcagggagcg
17520cacggtcagg ggcaagttgc gggggtcggc gggcgaaggg aaaatatagt tgtcgcccag
17580ctccgcgcta cggtacgcga tcgagccgtt ctgggctacg aacagcagca cgggcggggc
17640ccgcggaaag gggttgcgca cggcctcgtc gtcgccgcgc gtggagcgga acctgcccac
17700gcgctgaaac cagagctcca ggcgcgcacc gccagtggcg ttgtcggcca cgccgcagtg
17760cacgtacagc ggctcggcgt acgaggcggc cacggcctcg cgctcgcaga gcatccactt
17820gcgctccttc ggcggggctt tgctcggccg cggggggcga ggccgccccc cgccgctagg
17880tcgcccatcg cggctcgcgt tgccagcgcc gccgggtcgc ccgtcctcgg gcggggcggg
17940cggcggcgtg ctgttggtaa cgggcgggtc gtgctcggac acggacggcg gctccggcgt
18000ccccacgggc gtagtagcac cgggcgtgct gtcctctggc gtagcgtcgg ggctgttggg
18060cgtggggggc gttgcgccgg tggtcccagc ggagctttcc gtctcggttg gggacgggga
18120gggcggaggc gagggcgagg cttccgcctc ctcggcgagc ccccgccggg cagacaggag
18180cgcccaggcg aaaatagctg cgatcagcca cgctcgcccc agcgggccca tggcggacgc
18240gcggcgaggt ctcgggctgg cggtctctcg gcggtcgtgc gcgcgggtgg atccaagatg
18300gccgcgaccg cggcgcgggc tacattttta agggcgtccg ttttgtgctt tcgtggtccg
18360ggattgagca cacgcgcggc tgcaggcgcg ttaccgtcgg cggcagccgt tcattcgtcg
18420gcgcagaccc agcaggcccc gacgcagaag cacagcgcgg cgtgcagggc cttggccacg
18480tgcgccgcgg ccagccgtgc ggtgccgcgc ccgcagcgcc ggacccacac gcaggccacc
18540agcgtgcccg cggctgccga ggccagcgct gcgggcgcgc cgccgtccgc gccgcagagc
18600ggcagcgctg cgcccagagc gcagatgccc acgtgcgcca ttagcgcgcc gtccgcggcg
18660tcggcgcgcg cgtagcgcag gcagaggtgc tcggcgagcg cgacgccgtg cccgcccgcg
18720acgctgagca gaaccgcgcc gcgcgtgcgc cagcgcccac cgccctcgag cccaagcgcg
18780cggcccgggg cccagagcgc cgccgccgcg gctaaggcgg cggccgacag cgcgagctcc
18840gcggcggcgg cgcgcgccag cgcgcgcatg ggcacggcgt cctcgcgcgc gccgcacggg
18900tcagcggggc acgctgcctc gccgagcggc gccagagtcc gcagcgccgc gtaccgccag
18960atcttgtagt ggcaggtgtc ttccagcgcc gccgcggcgt ccgtggcggc gacgaccagc
19020gcggccgcgg cgcccgcggc cgccagcgcc tcgggccgcg cgccccagcg cccggccgaa
19080aggccgagaa gcagcccgca ggtcatggtc agtagcgccg tgcgaaagtg cgccccggtg
19140cccgaggctg ccgtcacaaa gtgcgcgcag tgcaccggca caccgcagac gacgtaggca
19200gcggccgcgc ccgttgttac cccgcgcagc acggcggggg cggggtctgt ggcccagacg
19260gcgagtgccg ctgcgacagc cagcgcctgc gcgagccggc caagcggcgc gagccggcgg
19320cgcagcgtct gtgcggcggg ccgccaacaa acgagcgcgg ccgcggccgt ggctgttaac
19380gcaagcgccg cggccgggtc ttgcgcgcgc ccgacggtgg ccagggccgc cgccatcaag
19440ccggtgtgtg tgcccatggc caccagcgcg cccgtggcgg caagcgcaca cgggccgcag
19500ccggctctcg cccccgcgca gccgctcacc cgcacggacg cgaacatgga tggtcccggt
19560tccccaaata acgcaacgtg gcccaggatc gtcttttatc ggcctttatt gtttttcgct
19620taaggagttt cgcccccctc cccgccccga tccgggcccg agctcgggcc cggggcgccg
19680gcgtcggcgc gcggccgctt gcgggcccgg ccgccggaaa ctgcgaccgg gtgcgcgccg
19740tcggtttgaa tgccggctcc ggccccgcga cgaggttggc cggacgcggc gggccgctta
19800gcgggaaggc ggggtgcggg ctcggcgcag tcatcagcat cgtcggcgga ggcggtggcg
19860gtggcggggc ggcagaaaaa gaacacagtc agcccctccg gcgccgctgt ggacacgctc
19920atcatggcgg cgctggcggg cgcgaggtag aagcgcagca gggcgtcgcc gccgacctgc
19980cgcacctttt gcagcagccg ccggaatccc gagggggact ccaactccag ccgaaagtca
20040ggcgccccgc cagagcagcg cacttccaat agggcggccc tgcggccgcc gccctgggcg
20100cgggcaaaaa tgcgctcgct gcctgcgctc ggggcgagcg ccagctggag ctctgccccg
20160gactcgccgc cctcatggcg cgcggcgaac gaagctcggc ccgatgcgga ctcggcgctc
20220aggcaacggg cgcgccggta tgcgaatacc accgcctcgt tgggatcttt ggcaactgcc
20280tgcagctttg agagctgcgg ccgcgagagc gagacggcga ggtcggcgcc gcgcgtcgga
20340agcatgattg agtactcgcc tagctcgtgc ttgaccaggc tggcctgcga tagggcatcg
20400gcctcccgaa agtaggtaac ttgcgttagc acgctcgcgg gtggctcacc ggtgattaga
20460aaggccacgt tctgcactgt ccgtgtcttg tcggcgcgga aggcgtccag caggccgcgg
20520cggctgtcga cgttggcgag gaagacggct cgcgcgtcgt cgcgggcggg ggcccactgg
20580aaggacgtga acttctcggc ggggacggcc acgtacactt gctcgtcgta gaggccgctg
20640tgtaccagca tgccctcgcg gctaaagacc aaaaaggcgt ttcgcagcga ggcgccaaag
20700gggctcagca gggcggagac gtccgccagc tggcggccga taagcgaggc gctcgcgatt
20760gggttgccgt tgccgccgtc ggacagaccg gcggtgaggc gggcctcgcc ttcgtcggcg
20820cgcagatgcg aggggggctg cagcatcgcg gcgggtgctt cggcggcgct ttcgctcgcc
20880tcttacgcgc gcggtcgcaa agcgagtctg cgctgcggcg gcgctcttta tactgggcgg
20940acgcccccgc agcggcaaaa cacacactcg gcggcctcag cgtatcaaac ggcgacacgt
21000ttaagtttcg acgcctataa gcgggcgcgc gcactaggcc tcccaatcgg caccgcgcgc
21060ggctgtgcgg gcgaccctgc gcagagagag atggggctct tcaagctact gcgttacgcg
21120tacggcaatc ggctggtaaa gcacgacgcc atcaccacgc cgccgggcgt gatgaccccg
21180atcgcggtcg acctgtggaa cgtgatgtat acgctcctgg agcgcttctg cggcgacgcg
21240cccggcggcg taggagacgc cgccgcgacc gcgcgctgct tcctctcgct gctgcggatg
21300ctgctcaagc gctcctacta cccgatcttt gtagcggacc gcggcatcca cggggaccgg
21360cgcgccacgc ggggtgccaa ggccattgtg gcgcagacga tgcgcgccgt cggcggctcg
21420ggccgcctcg ggcggctcgt cagcgacgat tatacctcgg aggacgaggt gctgggcgcg
21480tacgagtacc ccgtcccgca cgcggacgcg gcagccgacg acgacgagga ggcaacggcg
21540aaggaatttg ccgggcgcgc ctcggcgggg gccgcgcggg ccaacgcgcc caagctggca
21600catcgcgtgt gcgtgagcct catccgcttt ttgggctacg cgtacgtcga cgccgctgag
21660atggaggcag acgacgtctg cgcaaacctc ttccacacaa acaccgtggc gcacatctac
21720acgacggaca cggacatgat ccttatgggc tgtgacctga ttttggacgc ggcgccgttg
21780ttccccccga cgctacgctg ccgcgacgtg ctggcgtcgc tggggctcac gtacggccag
21840ttcctcgcga cgttcgtgcg ctgccacacc gacttgcacc agccgccaat gttgcgctcg
21900gtgcagcagg tggtgcgggg gctgcggcgc gctgccgagg ccgagcccgc gactaccgag
21960acggagtctg gctccgagcg cgagccggag tccgagctcg gtcgtccggg cgctgggccg
22020cggcgccggt tgccgcccgc ggtcgacgac ccgctgaaaa ctacgacgcc ggcgaccgtg
22080gaagcgcaca gcgtgcgcat gaagtataca tctcggtacc ctccgattgc gcagacgtgc
22140gccgacgcgc tgcggctgct gccggcgtcc cagacgcgcg gcggcgtgct ggagcgcaaa
22200tttgtaaagc acgtggtgga cacgatcgcg ccgcgaatgc gcgggcgctg ggccgtgctg
22260aagcgcgtgc ccatcgcaca ggacgccccc gaccctcggc tcgtgtacga caccatcgtg
22320agcgccgtag gcagcgccgc cgaggccgac acgctgatgg ggctcttctg gaagcacatc
22380cccactccac ccccatttgc cagggtgctg gcagactact gggacgaggc ccccgcgggg
22440ccggggtcgc gacggacaac ccgccaataa aaacgcgcgc atacgcgaga ctggctttcg
22500ttgacatgga acatttttta ttcgcggcgt gggggtgaga aggaggagga aaggcggggc
22560gctctggcag ggcagcgggg gtgccctaca ggtcgttgat tacggtgcct gtgtagttgg
22620tgctgcggcg ctcaaagaag ttcgtgtgct tctcggcagt catcagggcc aaaggaaaat
22680cggtcccagg aggcggggtg ccaaacagag gaggcagctg gatagcagcg agcaggcggt
22740ccgcgctgta ctcaacgtac gcagaaatag cctccacgtc aagtatatga ctgccgcgcg
22800gcgcgcgtga ccaaataaac tcgcgctcaa tttccacagc ttcgcggaac agctcgtaga
22860tgcgggccgg cggcggccgc tccccgccga ggtagttgtt gaagatgcag cacgacgcgg
22920ccgtgtgcac ggcttcgtcg cggctgatga ggtcgttggt ttggcacgtc acgacgaaaa
22980ggttgtgggt gcgcaggtag gcaatcgccg caaacgagga ggagaaaaaa atgccctcga
23040ttagaatcat gagcacgtac ttttcggcca ccgactctgc cgcggccacg cgccgctcga
23100gccagtccac cttgcgccgg accgccgggt cgccgagggc gccctctacg tagcccgcgc
23160gcgccaccgc gtcgtttcta aagagcagca gctgtatggc gctgtacacc cgcgagtgca
23220ccacttcgat ggactcctgc tcgatatagt aatgcaggat gtctttttgg gtgaacagct
23280cggacaggtc cccgaggttg acgttcacga ggtcatcggc ggccgagagg aacgcgaaca
23340gaaagcggta aaactccagc tcggcgccgc tgagccgcgc cacgtccttg gcgtcgtccg
23400ccaggggaaa ctcggtctcc agccagcggt ttgcgacgct gagcgaccgc aagtgatcta
23460ggtcggggca ctcggtctcg taaaagtatt tgtatttacg cgtgagggtc gccgcgtccg
23520ccgcctcggc catcgcgctc ggcgcgtcgt cgctacaggt ggcacccaga gcacacgagg
23580tcgccgcccg tgaagacgcc gttgttggtg gccttgcgga tcttgcagta gtagagtccc
23640gtcttaaggc ccttcttata ggcgtacacc aggaggttca tgatctggga ggcgggcacc
23700tttccgtcca ttggctcggt cacgaagagc gacattgact ggctctggtc cacgaacggg
23760gcgcggtcgg cgcagaggtc gatcaggcgc tcctggtcgt actcgaaggc cgtcttgaac
23820ttggccagcg gatgcccggg cgcgaggtcg cccagcgcgg cggccaccga ccactgctcg
23880cggtccagcg cgcgcacggc cccgagccgg ctggcctcgc gcgtaaagtg ctttcgcagc
23940gcgcgcatca gcggcaggtt cgggcgcagc agctcgccgc tcatcgtgac cttgctgaac
24000atgttggtga agacgggcga gaagccctcg ctgccctccg tcacctgcga cgaggacacg
24060gtcggcataa gggcgacaaa ctgcgcgttg tacagcccgt gccgcgcgac cttctcgcgc
24120agccgggccc aggcccgcgg cagcgagagg accacgccct cgtagccgtc gaacggcatg
24180agcccgcgcg cgaacttgct gcgcgcaaag tcctcgaacg gcgcgcagcc gtactcgcac
24240agcgtggcgc tggtggccat gacggccagg agcaggcgct cggcgatctc cacgttcagc
24300cgccgcgcgg cgggcgagag catgtccatg ccgagctcca ggaggagcgt gtgcaggccc
24360tggaagccga tgcccagcga gcggtggcgc gccacgccgc gcgcggcctt ttcggtaggg
24420tactgtccgc ctagcatcat agcgttgaca aaaatggcgg ccgtggcggc cgccgtggac
24480agagcggcaa agtcaaaggc gagcgcgccg ccctcaccct cgcgcacgca gcgcggcagg
24540ttgacgctgg ccaggttgca cacgccgtgg gcgtcggggc tcgcgcgctg cacgatttcc
24600gtgcagaggt tggagcccgt tagcgcgtcc ccggccgtgt ccatgtggta atggcggtta
24660cacgcgtcct tgaacatgac gaaggggctc cccgtcatga cgatgcttcg gacgatgagg
24720aaagccaggt cctgcacggg cacggtctcg acgcctagcc cctcgcgctc cagtcgctcg
24780tactcggccg taaaggccgg gccgtgcagc cggctgaggt gcgacgcgcg gtcgtcgaag
24840agcgtccaca caacgccctc gcggccttcg aggtgggcga ggtagcggtc aaagagcagg
24900tccggcaccc agaggcagct gaacaggttg tcgcagcgcg tcgactcgtc ccgggcgagc
24960aggccgcgca tgtttagcac ggcccgcacg tcgcagtgcc agggctcgag gtacacgcag
25020atgcccgtcg ggcgctcgct gtcgctgttg atggccatgg ccatcgagtc cagcagcttc
25080agcgccccca tgatgccacg cttgcagtcg cgcgagaccg cccggttgaa gctctggaag
25140gagattccga tcccaccgcg gttgagcaag attcgcgcga cctccgtggt gatcgcctcc
25200acggcctccg tactgctgga cacctgcgga ttgagcaggt agcagctggc cagcgagccc
25260cgcgcgcggc cggcaaagag catgatcggc gtcgcgggga caacgagctg ccggtacagc
25320gcggtcaggt aggcgttgaa caccgcgcac cacgtggcgc cctcgccgac gagggcgcgc
25380ccaaaggccg gctcccgcat cgtccacgtg gcggcggtcg cggcgatccg cacgaagaac
25440tggcccatag actcgatcgc cccgccctcg agcttggcca ggtacatctc ttcgtacttc
25500agcgccgact gcaggccgag cgcgcgcagg gtggcgtact cggtaagctc gaagtatcgg
25560agcgagacct ccacgaaggc gcggttggcg cgcacgcgct ccgcgacctc ggacacgagc
25620gcgagctcgg ccgatgtaag ccagtcgtcc agaggcacgc tccgagcacg cacgcgcaag
25680tgcacgagtt gcccgcactt tacgtacacg cgttcgtcgg cccgcgactg cgccttcatg
25740cgatccacga cctcgccgac gtaagccgcc actgcggccc gagaaggacg agaagcggcg
25800gcgggcggcg gcggcacggc accgcagccc agctgcgccc attccgcgtg ctcggcctcg
25860agctgctccg ccgcgtcggc cgggcaggct gtctgcatga acgcgtcgct cgccatcttg
25920ctcgcccccc tcgcttgcag cccgcccctg ccgacccgct ggctttttgt ctttcgcccg
25980ccgacccgcc ggcgcttggt ctgcccgatc gcacccgccc cgacgccttg ggaacaagcg
26040cgcggccggc tctggctccc cggagataaa aaccgagcgt atggcggcag caaaaggtgc
26100gggccaggtg ctcgctcggc aggcaacctg ggcccggcag cagagatatt taacggcggt
26160ttgaggggcg tggcggccct tccctgttga tttatggcat cgcacacaac ggtgtttgcg
26220gaacacattt tatttaaaac gacagcgccc ccttgtgtca gtaaaagcac tccacccagt
26280ccccggttcc ccacaccaag ccctcgatct tgacgacggg cacgtcgcaa gactggtagc
26340gctcgctgcg gcaagtgact cgcggcgagt cgtggggcag cgtccccagg cgcgcgaagg
26400cggcgtacat gcagctctcc cgggtgggcc gcccggcagc gtccggcgcc cagcgcggca
26460ggaacgccgt cgcgtcgcag tcgcccagcc gcgagacggg gcagcggtag gccgcgcggc
26520tgttcgccag cgcggggagc ggaaactcgt ccgcggcccc ggccacttct gcagcgtcgc
26580ccgccgtccc ccggagcacg ttttcggcgc gcgtgcggtg cagcaagtag ctcagcccgc
26640tggcgaatgt ggtttcgtta agcttgctga cggccacgtg ggcgcgaaag ccctcgtgct
26700ccaagcgctg cgtgtacacg aagaccaggt acacaaattt gacgccggcg ggctccagcc
26760gcagctcggc gtccacgtcc aggaacgcgc aggcgggcac gtgggccgta gagcgcgggt
26820gcgcggcctg gtcagtgcgc gcgccctcct gcgcgccgca gacgacggcc gtgacgctgg
26880ccagcttgtc ttgcgtggtc cacgagagca gtccgcccag gcacccgagt gcctgatgcg
26940ggaacgcgcg gcagcggatc atggcctgca ggcaggcgta gaagcggtct agccgcaatg
27000ccatgcggcg gtcgccggag ttggaaatga ggtgcgcgcg cagcgcgtct gcggcggcgc
27060ggttgccgta ctcggcggcg caggcggctg ccagaaagga aaaggataca agagaggccc
27120gcagcccccc gggcggcacc gcgcccacgc tggaggcgtc gccgaggtcg cgccaagcct
27180cttcgacgtc gcgaaactgc cgtccggggg gcgcagccgc ggcggccagc ccaataatgt
27240cggcggggtg cttcagcgtt aggacgggcg cgccggggcg ctcgagctgc gggtcgcaaa
27300agtccgtcag ggtaacctgc cgcgagagcc ggatgtgagg ctgcccgccg ggcgagagga
27360cggcggtgcc ggcgggcgtg tccacggcaa tctgccgggg cgtgacgatt tgaatccccg
27420acatgttctg gatggttacc gttgcgtcag acacgtgcag catcccgccg gcccaagggt
27480tgtagccccg gggtgcccgc ccgcgagcgc cgccaaccgc aggcgccgtc actgactgca
27540cgccggcttc ggcggcagag gcctcggccg ccgccgcggc ggcggcgggg acgcccgaga
27600acggcggcgc ggcggctggg agccgcatcc gcaagtggtt gccgatttga atgtaactcg
27660agctcccgtt aggcgcggcc atcgttcctc gtccgctcgg cactcgcgct cgggtcgggt
27720gttatagggt ggcggattcg agctgccttt atagcgccgg cgcacgcggc gggggcaagg
27780gcgtcagcgg cggaagccgc ggcggcggtt gcggcggggg gctgtgcggg gcgtacaata
27840aactgcgcgg cgggtgcggg ctctggccat tcgcgccccg gcgcacgcgc ggctgacatg
27900agcggagacc ccgtgcgggc cctgtgggcc gcgctcgagc ggttggatgg cgaggtcgcc
27960ggcccggccg cgcttgcgga ggccagggcg gccgtctcgg agttcctcct cgcgtccggg
28020cccagctcgc tagacttcgt ggcgccgcgc tgggccgcgc tgcagcgcgc ggcgtgccgc
28080gcttacgagc gcctgcacac gccagacgcg gcgctgctgg cggaaaacct gcccggtctg
28140gtgctgtggc gcctgcccgg ggccgcgcgc gacaccgccg atttcatggc cggcgttcgg
28200gacctggcca acagcatgat cgccgaggcg ccgttgggtt acctggcggc cgcgcgcctg
28260cgcgccacgg cggcgttcgg cccggtgaac atgcagcgcg tggtggtgga gtgggcctcg
28320ctctttttgg agatctacgc acgcgaggac gcggcgtgcg tgggtgtgtt aggccccgac
28380cctgcgtgcc gctcgccggc gggcagcgcg gccgtcatcc gcccgctgct gcagagccgc
28440ttccgcctgc tgtatgacat gccctttttt caggcggggc ttagcgccct ggcgcacgcc
28500gccaactgga aagtgcctat ggccgccgtg gcacgacgcg ccgcggacgc cgcggcgccg
28560ccgctagcgc gcgcgctttt tgccgtggcg cttgtcgacg agtactttcc cgagccagac
28620gacgaggaca cggcgccggg gctggctgag gcgtttgcgg aaattgctga cttggtgccg
28680cccgaggcgc tagtgcccgc gggtgaggct aacgcttttg cgcgctcgtc gcacgacgtg
28740cgcgtatcgg cggcgctggc ctaccgggac ccctttgtgc gcggcgcggc cgcgggcagc
28800gtcgccgcgc gcgtgcgtgc cgacgcgggc cttctcgccg acgacacgtt gctcggccgg
28860gacgccgtcg ccgttcacgc aggcgcggtg gtgcggctgc tagaacgcgc ggccgcggcc
28920gcgcccgcga cgccggcggc gctggggcga gttgcagagc acgcggccgc cgtttgggac
28980gccgtgcagg cgagcgccac gccagaccaa gccgtggaga cgctggccgc ggcggggttt
29040acgccgggaa cgtgcgccat gctagagcgc gccgtgctgg cgcagctatc gcgcccagag
29100ccgcgcgcgc cggcagacgt gctgcaggcg gtgggctgcg tggcggtggc gggcggcgtg
29160ctgtttaaac tctttgacgc gtacgggccc agtgcggact acctcgcgca ctacacggcc
29220actatcgcaa acctgcaccc gtactacgcg gacgtgctgc cgttgctggg gctgcccgac
29280ggcgggctgg agcagacgat ccgccactgc atggccccgc ggccgcgcac ggactacgtg
29340gcggcgattc gcgcggcgct ggcggcagag gccgcggccg cggacaagcg agccgcgagc
29400gcgagtgcgc gggcggccgt tgaaaacagc ggcgaccgcg cggcggccgg agctgccgcg
29460cgcgaggccc tcctaacctg gtttgacctg cgcgccagcg agcgctgggg cgtggcgccg
29520cccgcggccg aagcgccgcc cgcggccgag gcggcacgct ctccggccgc gggcggcgct
29580tcggccgcag agctcgcccg cgcggcgcgg gcgctcgagt tcccccgcac ggacgccgtg
29640ccggctgccg tcttgcgaga cccggccttt gcgccccact tcgccgccgc cgtgctgtcg
29700gacgtgctgg tggctgcgga cgcgctgccc ttcagcgcaa acggcgtggc gcagctgatg
29760gcgctgatcg cttgggcgcg agactgcggc gcgggagcgg tggccaacgt agacggctac
29820cggacaaaac tgtcggccct ggcggccggg ctctggccgt ttgtggacgc gagcgccccg
29880gcgcccacga cgacgcaggt ccgcaacgcg gaggctgtgc tgggcgagct gcacacggta
29940gctacgaccg cggcggagtg cctgccgccc gaagtgcgcc cgcctgtgcc cgcgcgcccg
30000cgggtgggcg gttgtgtctt cttagcgagc atgtacctgc acgccgcctt cgcgcggctg
30060cagggctatg tcgccgagac ggaagcgctg gccgcgtcta tggccgcggc cgtgggcgac
30120gttgccggcg cggtggcgcg gctgggagtg ctgttcgact gccactttgc gtcggtgccg
30180gggcagcaga tgctggcgat atacgcgacg cgcggcgcgc cgtgcgccct gggtgcgtgg
30240cgctcggcgg acctggccga cgcggtgcgc ggcgcgcgcg ccgaagccga gcgcgcccgg
30300gccgaggtgc gcgtgtcgct ggcggcgttg cagcgcgccg cggcgcagac gacacaagcg
30360ctgcaggagt gtgaagctgc ggacgcccgc ccccccggcg gcgggctgga cgacgagcac
30420cgcgcgttgc tggcgggcca ctcggcgctg gtgcgggcgc agacggcgct ggcgctggcc
30480gccggcaagc tcgtggcggg cgcggaggcg ccggggctgc acgaggtggg ccgctttctg
30540cagcgctggg acgcgatcgg cgcggccctc gggcgcgcgc tagacgacag tgccggcgag
30600cgcgacgtcg ccgagctcgt cgcgcggctc cgcggcgtct gggacgaggt ccaggaggac
30660cgccgcgtag cggccccggg gccgccgcgc agcgccgcaa acgcggcggc cgccgaagag
30720gcggtgctgg cgctgttgga gggctacccg gaggttcggg gagacgaggg cagcccggcg
30780ctcctggacg cccgcgcgga cgtggccgac tgggcgggcg tagaccgcgg cccgctgcag
30840cgccgcgcgt ctgcgggcgc ggacgccgcc gcgtctgccg ccgcggcaaa cacggcggcg
30900gggccgtggc ttacgacgga agacctgctc gccgaagtcg atggcgtttg cgccagtcgc
30960ccggccgcag cccggtgagg cgcgcgccgg cggtgcggcg ggaggccttc gcataaacgg
31020cgctgcgcgc gcggtgcccc ctagtacccc tgtggagcag cgaagcggca ccatgtccgg
31080cgttgccggc gcgcgcgcgc cggcaacgcc ggccgacgtc gcggtcgccg ctgtgggttt
31140tcgcaaccag tacgacgcgg cgctggggcc gggcagcgcg gtggcatgcc ttcggtcctc
31200gctgtcgttt ctgcggctgg ccttcgcggg cggcgtcgac gccgcgctgg gcgccgacgc
31260catcgacggt gctctcgctg agggcgcggc gtgggcgcgc gaaagcgggg cgcgcccgga
31320aatgtgctcg atcgtgcacc tgccaaaccg catcaccgac caggcgggcg cggggagcgg
31380gctctgctgc gtgttttcgc gcgtgtatgg ggagtgcggc ttctacacgc cgccggcgga
31440gcgcgccctg agcacccaag tcccagcgcg cgaattcgtg gacgccgtct ggcagccgcg
31500gcggacgtcg ctggcgctgg tgatcgtggg cgccatgggc gtcggtgtct ttcgcgccgg
31560cgacgcggtc tacctcttcg acccgcatgg gagcggggac gtgccccagg cgtttgtcgc
31620gcgcatgcgc cccgaggccc tctacgcgta cctagctctg cgcgcgtgtg gccagcccga
31680gtcccggtgg gcgggcgcgc tagtgcactt tgtttcggcg ggcccggagc ccgcgcgccc
31740cgaggagcta agggcggccg tgtctgcgct gtacggcgcg agcgagacat acctggacga
31800cgagccctat gtcgagcggc gcgtggtcag cgtgcacccg cgcgcgccgg ccaacacggc
31860ctgccttacg gccgtggcgg tgggcggcgc gggggcagag tgcgaggacc ctacgttcgc
31920gcgcccgggc tcgccggcgt tgctgccggc ggagcccgtc gcgcggatgc cgccgcagat
31980cacggccgcg gccgcggctc gcgcggcggg taagcggacg agcctgccgc ggcggcggcg
32040ggccccgtgg acgccgccct cgagccgcga ggaccttcgc gcgccggcgg cccgcgctcg
32100cgcggggaag cccccgcgaa aggtccgggg cgcggagacg gcgggggccg gggaagattg
32160gggggagggg ggaaacgcgg ctgcggcccg cccgccgccg gcgctgggcg ccgccgcgcc
32220cgcgcacgcc gcgacggcgt gcgcggcgga gcttggcgcg cgcgcggcgg aggttaccgc
32280ggccttggac gccgtccagg cgcacgcggc gtcgatagcc gctgacgcag acgcgtgcgt
32340ggctcgcgcc gtccgcgtgg cgcggccccg cgacgccgcc gcggaacggg acccgctgga
32400acacgcgatc gcgggcctgt ttgagcgggt gctggccttt ttggtgcaga acggcgcgcg
32460cacgcggcac gacgccccgt cggccgtcca gccgcttttc ggggcggtgg cccaggcgct
32520gccgcagcac acgcccgcca gcgcgttcat cacatcttcc gggatggtgc tcgaggggct
32580ggccgcgtac acgcggctgt cggaggcgat gcgcgcgcag ccctcggcgc tgggcgacct
32640ggcggacgcc aagctgcgcc tagtcgcggc cgccgtcgcg gccgacacgg agcggctgca
32700cgacgccgtg gacgagctgg agggcgaggt ggacggcgcc ggcggcgcgg gcccgctcga
32760gctgtgcggc gccgtctcgg cgcgcttcat ggagcgcctc tcggcctccg gccggcggct
32820attttcgcgg gcggcgcttc gcgacggccg gccgctggac gcgcgagtcc gagcgctctt
32880tgagcgcgcg cgagcgcgcg aggcccgcgt ggccgccgag accgcggcgc tcgcgcgcga
32940gatcctggcg ctggagggca cggtgcgcgc cgcgcgcgag cgcctggacg ccgtcccgcc
33000cgacgacccg cgcgcggtgc ccgcggacag cgcggtggcc gacttggcgg ctgagcttgc
33060ggcgggccgc gccgccgtgg tcgcgcggag tgccgccgcc ctctccgccg agctggacgc
33120gctcgcggcc gaggcgctgc ggcagtactt tctgcgcggc gcgcagtaca gcgctcgcgc
33180catcctggcc gaccgcggcg gcggcgagcg cttccgcgtg gcgagcgcgg cggttgcgcc
33240gctgcagcgg ctggccggct ctgcgcccga cttggcggcg cgggtggctc ggcttggcgc
33300cgcgccgggc gccgcggcgc ctccgctgcc gcggtccgcg cgcaaaggcg agctcctccg
33360cgacctgctc gcggcaggcg caacggcgca caccgaagac ggcctcgcgg cctgggtggc
33420gctgctgcac gaggcgcagg cggaaggcgc tgccgccaag aaggagctgg acgccgtgct
33480gagtgacgtg gccgccataa acgggcgctc ggcgtcgcgg gcgtcgctgg aggcgagcat
33540ggctcgcttc gaggcgatgt ccgcggcggc ggcgcgggcg gcggcgggcg ccgccgcgga
33600ggcgccgggc gcgggcgccg aagaggcggc agacgccgcg gaggcggccg tgcgcggtgc
33660cgacgacgtc ctgcgccagc tggacgccct ggcgacgggc gcggcggctg accgcgaggc
33720gcgcgcgcgc gtggccgcgg cccgcgcggg gctagaggcg caggcgctcg cggcgcggcg
33780gcgcgtggcc gagctggggg agcgacgcgc agagctgtac cagcgcctgg acgcgctgtt
33840gctgccgctg cagggcttcg cggggctgcg cgcggcgccc ggcgcgctgg agcggctgtg
33900cgcagacgcg ggcgcgcaga gcgcagagga ctgcgcgcgc ttcttgcagg aggcgccgcc
33960gcgcgtggcc gcgggcgtgc aggaccgcct gtggcagctc ttcggccggt accgcgaggc
34020gctggagaac ccgagcgcgc tggcgccggg cgcgctggcc gggctgggcc cagccttcgc
34080ggcggtgctg ggcaccgcgc tgggccaggc gatgggcccc gcggcgcgcg cgtttttcga
34140ggggcacgcg gagcgcgtgg cggccgccgt ggctcgcgcg gcggcggagc ctgcggcgcc
34200tgccgcggtg gccgccgcgg cgagcgcgct gcgcgaggcg gctgaggcgc tgcgggccgg
34260gggcgcgcag ctcccgcccg agtttgcgtt tttggacgcg ctgcaggccc agtacgcggc
34320gcggcgcgag gcgcagaccg gcgcgcggcg gctgggcgcc gcgctcgcgg ccgtcagcga
34380ggcttcgggc gcgcttgcgt ctgcggcgag cgcactaaaa aacgccatga cggcgggcgc
34440tgatgcggcc gaaacaacgg cggccgccgc cgcggcagac gcggcgctgg gggcggcgga
34500agaagtactt cgggccgcgg acgaggccgc ggtggccgcc ggcggcgagg atgcggacgg
34560cggcgaggat gcgagcgagg ccgacgcgga cggcgccggc gatgcgccgc ccgccgggcg
34620cttggggcca caggccgcca agctgcacgc cgacctgcgc aaggcccggg cgctggcgcg
34680gcggcgcgcc gaggaagtcc ggcgcctgcg cgccgaggcc gagcggcgcg ccgagggggc
34740ggccgcgcag cggcaggagg agcgctggcg cgaggacttg cgcgccgcgc tggagcgcgt
34800cgaggcgaac tccgccttcg acgcggccga gctggcgcgg ctgcgcgccg cggccgcggc
34860gcgcggctac gacccgcggc cgctggcgcg gcaggccgac cgagcgctgg aggcgagcgc
34920gcagcgggcg acggcagcca tcgaggccgt gctcgcgttc aacccgcacg cgcccgagaa
34980cgcgaagatc gatgtcccgc cgccgctggc gcagctgcgc ggcatcgcgt ggtgggacgc
35040gttttccctg gcggcccccg cgctgtcggc cctcttcccg gccgcggacg tgggccagct
35100gacgcggttg atgcacatcg cgacggggct gctgacgttc gccgcctcgg gaggcggcga
35160gcctcgctac tacgacgccg taacgtacct ggagggcgac ctggcggccg tgcctcggct
35220cgccaagtac gtggccttct accgccgggg gcacgcggcc ttcgaggagg agcgcgcgcg
35280gctgggcgcc ctgcgcgcgg acgtgctgca ggcggccggc gggcgcgcgg cggagatcag
35340ccgcgcgcta gaagaggtaa cgtacgtgcg cagccccgcc gaggcggcgc gcgcgctgga
35400agcgggcgtg cgcctggagc tgccgagcga ggctctgatc gcgagcgcgc tggcgcagct
35460ggagcgcttt gaccacgctc gctttgccgg ctcggcctac gaggcgcaga tgctgagcac
35520ggtgcggcgc gacgcggccg cggcgcgaga ggcgctagag gcggcaaagg cggcgcgcgc
35580ggaggccacg gcgcgcgccg agcgcatcct cggcgaggtc gtggctgccg aggcggcgcg
35640cgaccgcgac gagggcgccg ggctggccaa cctcaagaac ctgctgcgca tcacgccgcc
35700gccggcggcg ctggggccag cgctggaccg cgccgcctcg gcggccgacg tcgtgacgca
35760agcggcgctg ctgctggcgg ccgtggagga ggcgccggag ctggacgtgg ccgcggtgga
35820gtggctgcag caagcgcgct ctatcatcga ctcgcacccg ctaacggcgc gcatcgacga
35880ccgcgggccc atggagccct ttgcggagcg catcgacgcg ctgcgcgagc tgaggcgcca
35940cctcgacgcg ctgcggcggc agctggagtc ggcggcggcg gcgtgggacg gcgcgtggga
36000gctctttgtg gcggcgcgcc gccgcgcggc cgcctcgcgc gaggaccacg agggcgccaa
36060ggcgcgcgca gccgcgctgc aggcggccgc gggcgtggtg ctggggctgc gcgcggacga
36120gcactacgcg cggctgccgg ccgcgttcac aggcgcgctg gacgcgcggc tggcggagcg
36180cggcgacgcg ctgggcgcct tccacgaagc cgcgcgcgcc gcggacgcgg gcctgcagcg
36240gctgcaggca acgcttgcgg cggtgcgcgg cgaggccgcg tacgaggggc tgcgcgccct
36300cctggcggcc ttcgacgcgc aggttgccga gctcccggcc tgggccgccc aggcgcacgc
36360gcccttccgg gatctgctgg tgctgcggat gcgcctctac gaagcctact ttaagctcgt
36420gccgcgcgcc gcggcgcgcg cacgcggcgc cgccgcggcc cgggcagcgc gcgccgcggc
36480gacggtgcac tcgcgcgcag accctgcgac gcgcgccgta gcggcgcgcg cggcgcggct
36540gtgtgagcgg gacctgcacc tgcgcgggcg cgtggcggcc cttctgggcg acgaagcggc
36600ggtgtgcacg ctgcgcgagg cggattcgga gattgacgcg ctggcgccgc gcgcctacct
36660ggacgccgac ggcacgccgc tctgctaccg ggtgtgctac cgcgcggtgg gcgacaagct
36720ggctgtggcg ctgtgctcgc aggtgggggc ttcgatgcgc cccccgctgg acgagagcgg
36780cgtggtggag gcggcttcgg tcgccgccgt gaacgtgtta aacgagattg tgaacctgcg
36840cctggagatc gagcgcgccc gcgacgcgga ctttggggcg ttttgccgct tcgtgcgcca
36900ccggcgcgcc gactgggggc tggcggacgt gcgctcggcg gcggccgagc tctacgcggg
36960gctgctggcg actacgctgc cccgccgcca cggcgtcgcc tccctgggcg cgctgtgctt
37020ctcgctggcc gagcgggggc tgcggccagc gcgggcgccg gcgagcgggc ccgcgccgag
37080cggcggcggc gcgctcgagc tgacgcccgc ggacctggtc gtggccgcgc tcatgggcgc
37140cttcatgcac ctggtaaact tcacgcgcct ggacctcgtg cagaagcagg agtacatgtg
37200caagacgttg gacggcgttc tgaccgaggc gcttacgagc cgagtggcgg tcaacagcct
37260cgcgccggga gagcccggtg cgaggcgccc ggtgccgctt ggcggcggcg cggacgaccc
37320ggcggacggc gcgctgttcg ccatccgcgc cgccgactgg gacgcgggcc gcctttcccc
37380gtccgacgtg ctagccgtgt ggcggcacgc gcccgacgcg gccacgcgcg cgaccgtggc
37440ggagctggcg cgtctcatcc ccggcggtgc gctgacaacg atcagcgtgc tggcgcgcat
37500gtgcattccg ggcgacttgc tggcggcgct gtggacgaca ctcgcggtgg actcgctggg
37560cgcacagacc cagagctacg acgccttttt ggcgcgccgc ctggacgcac cctcgacggt
37620gcacgcgacg ggcggccctt cggaagacgc ggcggcgctg gccgctgcgg ctgcggcggc
37680cgggggccgg cccgcgctct tttgcccgac ggggagcagc gtgacgttta cgctcgtgcg
37740gcagccgccc agcgaggtgc agaccgtcaa cgcgctggac ctcgtcacgt gcgcgctgct
37800gctgggcgcg ccggttgtcg tggccatgga gaacccggac gtgttctcgg agggctcgcg
37860cctgatcatg tgcctgcggc tgtttgacac gcggccgggc gggcgcgacg ccgacgcgcc
37920tgccgccgtg tcatcggacc taaactcgtg gggggagcgg ctgctggcgc tcgacgagaa
37980cattatcgaa aacgcgtgcc tgacggcgca gctggagcag ctgtcggcgc tgatcgcgag
38040caagccgcta cgcagcgcgc cgccctgcct cattatgctg gatacgcatc tgcagctcgc
38100gcgggtgctg tgggcgcgcg ccgccgcgcc gccgctcgca atgttgaaga ttgccgaaga
38160cgacgtgctc cgggacttgc ccagcctgac gctagactac gaggacgcgc tgccccccgc
38220ggccagcgcc gccgacccgc tcttcacgca catcatcagc gagaacaacg tcccggactt
38280tgccgccgct agcggcgacc cgctatacgc gcaccccccc gtgttccagc acgccaccga
38340caatttattt ccgcacgcgc gggcggcggc aggtggcggc agcggcaacc gtgtagccaa
38400cgcccgcgcg gtcgccgccg ctgcgcgccc cccgacccca gcttcagccc cagcgccggc
38460accggcactg gcaccggctt cggcggagcc tgctctcgct tggggggccg acgagtggct
38520agacgacgag attggcgacg cgtacccgcc ggcccccgcg cacgacgcgt acccgccggc
38580ccccgcgcac gcgcaaggaa aacccgcgtt actggcagcg cctgctgccg gagccgcgga
38640ggctcctggc gttgagcgcg cgcgtcgcct gacgcgccgt actggaccac ggaagtccat
38700gcccgccgcg ttgccgtggc gacgcccgcc gcccgcaagc ctggtctccg cagcgcctcc
38760agtgcctccg gggccgcgcc tgccgccggc cccgccattg ccgccgccgg ccccgccatt
38820gccgccgccg gccccgccat tgccaccgcc ggccccgcca ttgccgccgc cggccccgcc
38880attgccgccg ccggccccgc cattgccgcc gccggccccg agtacggccc cggttccggc
38940cccgccattg ccgccgccgg ccctgactcc ggccctgact ccagccctga ctccggcccc
39000gactccggcc ccgccattgc cgccgccggc cccgagtacg gccccggttc cggccccgcc
39060attgccgccg ccggccctga ctccggccct gactccggcc ccgactccgg ccccgactcc
39120ggccccgcca ttgccgctgc cggccccgat tacggttttg gttccggccc cggttccggc
39180tccggccccg attccggctc cggccccgac tccggctccg gccccgactc cggctccgcc
39240attgccgccg ccggctccag atggggccat gggagcgctt agcgcaacgc ggcggccgac
39300gcgccgcgct ggggctcgaa aatcgctgcc ggccgcgcag ccgcggcagc ggctgctgcg
39360ctcacgctcg cccgccagcg ttccggcgcc gggctcagag ctcgttccac caccgtcagg
39420cggtgcgctt ggctcgcccc cttctttcgt gccgtccaga ccgcctagct tggagcccgt
39480gcctggcttg cccctgccgc cgagccgggt ccaagcacca gtagatgcgc ccgcgccgcc
39540ccccgcgcca gagcggcccg cgccgccccc cgcgccagag cggcccgcgc cgccccccgc
39600gccagagcgg cccgcgccgc cccccgcgcc agagcggccc gcgccgcccc ccgcgccaga
39660gcggcccgcg ccgccccccg cgccagagcg gcccgccaca gcggtccaga gtggttcaaa
39720aattccagca ccgtcgaatg ctttggtggg ccaggtggcc ccagcgctgc tgcggcgcgg
39780ccccagcccc aggggcaagc ctggcgcgcc cgccaggccc acgggcggcg caaatattgc
39840gcggaaaaac acccgggccg ttgaccctac cgttatcgga tctggctctg cgctgtcggg
39900ccttggctcc gccgaggagg atgctgactt tggagcgtcg ggcatgtatg ttgcgccgcc
39960tggccccgct cccctggctg cgccccctgc gccttcggcc ctgccggcgc cgcgcctgga
40020ggcgccagcg gccgcaagct tgccggcgcc cccgatcgcg cccccgatcg cgcccccgat
40080cgcgcccccg atcgcgcccc cgatcgcgcc cccgatcgcg cccccgatcg cgcccccgat
40140cgcgcccccg atcgcgcccc cgatcgcgcc ccccgccatg ccggcacccc caagcgcagc
40200gccggcgact gcaggctcgt ccgcgccccc aatcgcgccc cccgccacgc cagcgcctct
40260aattgcaccc cttgccgcgc cggtgcctcg gttggtaggt gcggctgcgc gtgggcgagt
40320gattggacac atgcgcgcag ctgcgccaaa gccgcggggg ctgcgcgcgg cggaacggcc
40380gccgatgcgg tcgtgggcgt ctcggggtaa cctccacacg caagatttac tggcaagcgc
40440cgaagcgcgg atttgcgagc tgcccgcgcc ccccaaggtc cccctcggcg cagactccga
40500cgccaccgat agctccctgg acggaagcgg gccggaaacg gaagaggaga cagaagcgga
40560agcggggggc gacggccccg gccaagacgc gcccaaagcc cgagtggtgc ctgccaactc
40620gctgctgaag cgccagtact tgcgcggcac gggcataagc gtcctggccc tcttgctgga
40680ggcctgcgaa aaaattgccc ggcggctgcg cgcgacgcgc gacgtgctgc ggcagcgcgc
40740cgctgaagtc acggctgaca tatttgcgct gcgcttgctt ttggggtagc gctcgccctt
40800tcccctcggt ccctcccttt cccccacgtc cgccgcgcct cgcggccttc tgtactttgc
40860cgcacaataa acaccgcaac gcaaaatttc atgagcacaa aactgtttta ttattgcgat
40920cgcacaattg cgccgatccg aaaaaagcgt cacgtgcgcg cggcagacgc cgccgcgcca
40980gcgtcctcct cgtattcggg ggggagctgc accacccggg ggaggaaggt ccgcttcagt
41040ccgattgtcg ggcgcgccca atgcgcgtgg tcgtaggtcg caaacatggg cacgcgcggc
41100acaacggcct tttcgtgccg ccgccgcagg tcgaccatgg ccagcgacgt gccgacgagc
41160aggttgcgcc gggccgcgct cacctgctcc ggcgtcgtgc cgtcctgcaa cgggcgcgcc
41220gcggcgttta gcacatgcaa aatctgcacg ggcagcaagt cccgcagggt gtcgggggtg
41280atggtagccg gcgcactagg gtcgatcccg gcaggcgcgg acatggcgtc gtcgaaccgc
41340gagtgagcgc gcggcgcggg cgcgcgtgtt aagagggcgc ccagaaaagg cgcagtatcg
41400cgagaatgcc gcaaactccg cccacaagtg ttgcaagggc tgccattttt tgccggcgcg
41460cggtcagcag cgcgccggcg tagtgcgcga cgtttccggc gccgccggcc ggttcgagct
41520ctcgctcgct gtgaccgcac gcgcttgcgc gccgagagcg cacgtcacgc tcgctcagcc
41580gctcccggac cgcgcggtct agcagccggc cggtgcgatg cgagtcgccg gggcccatga
41640accggaacga gagctgcacg cgcggcatgc gcacgaagca gctcacggac atcatggcgc
41700gaaagggccg tgggtctatg ccgccgcggg ccttgatctt ctccagcgcc gacaggctca
41760ggcccgtgct ttgcgtcgag gccagcgtgg cgttgttctg ctccgccgtg atggccgcga
41820gcggcgcgcc ggggggccgc gagaagtacc cctggaagag cacggacacg cccgtgttct
41880ggacccggac gtaggggtcg cagtccgtct gcgcccagct ggccattagc cgcaagatgt
41940actccagggg gaaggactcg ttgcttccgt cctggccgtt gaactggaag acgcaccgcg
42000cgggcgggcg gcgcgggtcc cagggctggg gcacgtcccc ctcgccacat tgcaggttgc
42060cggcgaccag caggcgaatg cgggccataa gactccggga agaaccctcg ccctcgccct
42120cgccgtcgca gtcgcgctcg cggccgtgca tagtgggcgg cagtctgtct cgccgagcgc
42180tgcgtcggcg cggaacgaag ctgcgccgtg ccggcgcggc gcctttatag cccgccccgc
42240tttgcggggc gggcccgggg cctacgcgtc gtgcagaatc tggtgtaggt ccagaaattt
42300gttgatcacc gtcgcaaagc gctccttcct cgcctccagc gctcgcgtgt ggctgcacgc
42360cgcccgcccg cccgagccgt gtgcgatcgt cgaggccagg cgcgccgaaa aggccaaata
42420gttcaccttg gcgtcggtgg tgggcagcag cacctcgagc tcgcgcggcg ccacgtcctc
42480gaaccaaatt tctacggcgg cgccttcgct ttggaggtag cggcgctcca gctcggccac
42540gtcctcggtg gccagcgcct cgggggggat gagctcgcgg agccgcatgt tcgcgcgcgc
42600tgacgacggc gccggtggcg gcgatggcgc gcgctcgtgg gcagagggtg cgttccgcgc
42660cccgtacgtc gcgtttgacc cggcgctgtt gaaggaaaac ggccagctcc ttgaggagct
42720cgtctttgcg gcccatttaa tggaggtgcc aagccctcga gacgacgggg acgaggacgg
42780gggtggtgac agggacggcg ccgccgcgga ggggggcggc agcgccgacg tcgtgccctt
42840tgtcgaagag gccgccgccg cgctggccat cgaccggccc tgcgccgtgt gtcgcacgat
42900tgatgcttac cggcgcgagt tcgggctggc gcccccctgg gtggccgact acgccatgct
42960ctgcgctaaa agcctcgcgg cgccgccctg tgccgtggcc atcgtggttg ccgcctttga
43020gttcgtctac ctgatggacc ggcacttcct agccgcgcac cgcgccacgc tagtgggcgc
43080ctttgcgact cgggtgctga cgctggtgga tgtacacaag catttcttcc tccacgtgtg
43140cttccgcacg gacggcggcg ttcccggcaa caacgccggg aacgccgccg ggggggcgcg
43200ccgggccgcc gaaaaggtgc gctactccaa ctactccttc ctcatccaat cggcaacgcg
43260ggcgctgctg gcctcggcgg cggagcgccc ggaggcgccg gcggtgcccg cagacggcgc
43320gggcccgcgg gcgctgcgcc cgcagtcgct ggcgactgcg ctgctgagtt ggaaagagtg
43380cgcgcgcctc gtggattgct cggcgccgtt gcccggcggc ggtgggggcg cgcgggcggc
43440gcggcgcccg gggggcacct gctgcgacgc cgcgcgtgcg cgggctgcgg agtacgaagc
43500gcgcgctgcc gtgctgccat cgccgcgcgg cggcgacgcc gacgaagcgt ccgcggccag
43560cgccgccgac ggagcgcccg cggaccgatg ggcgtacgcg gacctcgcgc tgctgctgct
43620ggccggcgtc gcgacccggg gcgacggcgc ggtcgccgag cgcgcgatcg cgtcccgccg
43680cgccgccgtc gatcgctact gggcggcgcg cgcgggcttc ctcgcggcca acacggcgcc
43740gcggtttgcg cgcttcgccg cgggcgacgc gcgccccagc gtggcgctgg ggccggtgct
43800ggccacggcc ctcaagcaca ttacagggcg cgggcgcacg acgggcgagt gtgtgctctg
43860caatcttctg ctcacgccgg cgcactggcg tgctttgcgc gcgctgcgcg cggacgtggt
43920ggcgcactct gccaacaacg cgggcctctt cgactgcatc ctgccggtgc tggacgcgcg
43980cgccggcgcg ccggtcgagg gcgacggcgg ccgcttcttt gccgcgctgg cgctgctgga
44040gcccgaggct gtgtataagc acctattttg cgaccccatg tgcgccgcgt gcgagctgca
44100ggcggacccc gaagtgttgt tcgcattttc cgacggcgac gcgcgcgacg cggacgagct
44160ggatctatat aaggcgcgcg tggccagcga gaatagtttt gagggccgcg tgtgtgcggg
44220cttgtgggcg ctcgcgtacg cttttaaaac gtaccagcgg ttccccccaa agccgaccgc
44280gtgtgcggcc tttgtccgag acgccgggca gctgctccgc cggcacggcg tggctctcgt
44340ctcgctggag cacaccctct gccactatgt ctgaccgcgg ggagcgccgc cgagctagag
44400agccaagccc agactttggg tgcgggcgtg gggctgagcg cgccggcgac tgggcaacgg
44460ccccggcctc gacaccagcc ccggccccgg ggcgccgctc gctgatctcg ccccgccttt
44520gctctcgctc tcgctctcgc tctcgctctc gctcccgctc gccgtttgcg cctcaagggc
44580gctcccgctc ccggggcccg gccacgcgcc gcgagcggct gcgttcgcgc acgggggcgc
44640ggcgcgcggc acgcgcgcga gacagctacc tgatgtactt caggtttttg gcctcctccc
44700ccgctgacga gctggccgcc gtccgcgagc tcgcggtgcc gcttatccga acgacgcccg
44760tggtgctccc gttcgacctc tcgcggacgg tcgccgataa ttgcctatcg ctttcgggca
44820tgggctacta tctgggcatc ggaggctgct gccccgcctg caccgtgacc ggcgagccgc
44880ggatgggccg cgcggaccgc gcggcgctta ttttggccta cgtgcaacag ctgagcaaca
44940tctacgagta ccgggccttc ctggcctcca tccgcgcgct tggcgggacg gacgacggcg
45000gctttggcgg ctgcgccccc ggccccggcg gccccaccga acgcgcgctc gccgaggttt
45060tggcccaacc cgagctcttt ttcgcctacc acgtgctgcg ggacgggggc gtgcgcgacg
45120cgcgcgtgct gttttaccga gacctggact gctcgggctt tatgatgtac gtggtgttcc
45180cgggcaaagc catccacctg caccaccgcc tgctggacca cctgttaacg gcttgtgccg
45240ggtacaagat cgtcgcccac gtgtggcaga cgatgtttgt gctcgtggtg cgccgggacg
45300ggggtggggg cagacaacag agcgcgacag acgccgaggt gccggcggtg agcgcggggg
45360acctttattg caaaatgtcg gacctcaact ttgatgggga gctgctgcta gaataccgaa
45420ggctgtacgc agcgtttgac gactttgcgc cgccggcgtg agcgcggcga agcccgccgc
45480ggcgagccgg ccttgcagcc ggcggtcgca ggcgcgcgtt tccggaataa agcgcttgag
45540caggttctcc gtggtccgcg tgtcgtttcc aaacagggcc ttgaaggtgg cgccgacggt
45600gcctaggagg tgggaaaagt agtagtctgt gttgaggggc acggcatggg cccgcgcata
45660ccccgggtcc tcggccatgt ccgagattag caaacgcccg gggcgggcgc cgccgccggg
45720cggcgcggac ggggccgtgc cgcgcagcgc gttcaccgcg gcggcgtcgc gctccacgcc
45780ctcgccgggc gcgacgatca cgtaggggat gcggtccttg acgttggggc gggcctcgct
45840gcgcagcagg agtttgtagt acacggtcag atgcgcgatg cgcttgttgg cgtaggcctc
45900cggtgggcgg ctcagctccg ccgtcatgac gaagtcgcca atgtccagcg ccgggtcggc
45960gatcttggcg tgagcttcgg ccaacacagc tccgaagcgc gcaaagcccg gcgggagctg
46020ccgcccgggc cactcgctgg gcggcacggc cgaggcctcg gccgcggcgc gcgaaacagc
46080gtcgtcgtgc ataagcacgt cgaccaagcg ccgcgcgtag gcgttgataa agcggcagtt
46140gtttttgcgc acgaggtcca cgcctttcat gagcatcttg ccgccgccga caaggccgag
46200gtactttttt tttgtgatga gcagcagctt ggcaaaggtt ttctcgcact cgagcttgat
46260gggcgggcga aagagcgccg ccgaaacccg gcgcgccatg ccgtcgccca gtgcgcacac
46320ggcgtcgtag ggcatccccg cgaacttgac aaagaccgag tccgtgtcgc cgtaaaccac
46380gcgcacgcgg tagcgcgcgc cggcggcggc cgccgccggc gcggccgcgg ggaaatctcg
46440caccagtgcc tcgggtgtgg cccagcgctc gtgtatgtac cgccgcgtct cgagcagcat
46500gtcgcgcccg atggtcgtta cggtggccgc gaccgccagg caaggcagta gtccgttgga
46560cacgccggtg aagccgtaca ccgagttgca cacgaccttg atggcggcct gctgcttatc
46620gagcagcaca gcctcctcgg gcgcggcggt ggggatgcgc gcgcggatgg ccttgcgcat
46680ggccagccag tcgcgcaaca gcacgctgag caggctctcg cgcacgtgcg cgcgcacaaa
46740gtggagcgcg cgcccgccca cgtcgaacgt cgcgtagtcc gcgccgggcg tcagccccgc
46800cggcgcggcc tcgccgcgca cgagcgtggt gaagcacagg ttgtgcgcct gaatgatgct
46860ggggtagagg ctggcaaagt ccagcaccat gacggggtcg acgtgaaagc ccgactcggg
46920gtccaaaacc ttggccccct ggtacccgac ggcgcgcccg cccgccgcgc ggggccggtc
46980cgccgcgccc gcgcccccct cgttcccccc gtcttcttct cccccctcgt cctcctcttc
47040ctcctcgccg cgagccgcgt cggcccagca ggcgaatgcc cccccgtccc cgcccggcgc
47100cccggccgcg ccggcctcgg ctccggcgag gcgcttttgg gtgtccggca gcagaaagcc
47160ccgctcccgg gccaagcgca gcaggcaggt gaatacgcga atctgctgcc cgtcaaaaat
47220ggcgcgcgac accgtgattc cggccagccg cgccaccgcc gacagctcca ggtggggcaa
47280gtacttgaag aacagctttc cgaccagcgc cgaatcttgg atgcagtact cgccgatgac
47340gccgcgcccc tcgggcccgg ccgcaaagtg ccgagggatg tccttgtagt ccaggtccac
47400cttccgctcc cgcagggcct cctcggccac ggcgttgagc ttgtagctgg gcagcttgag
47460cttctccacg gccgtgcggt acatgtccag ggaaaccacg ccgttaatct tcaccttgct
47520ctgcttctga aagcggtttt ggcccgcgtc gaagacgcgg aagaggccgc cccggtttag
47580cttcccgtag ccgtcgagcc gcacgtcgta gacggccgtg agcttctccg agatgtacgc
47640ccagtcgaag ttgacgatgt tgtacccggt gacgaactcg ggcgagtact gcttgaggaa
47700cgtcatgaag gccagcagca gctcgaactc gctgtcaaac tccagcacgg cgggcgcggg
47760gagcccggcg gccgcgcacg cgccgaggaa ggccggcggc aggtcgcagg atcccagcga
47820aaacaaaagc gtgtgctcgt ggcgctgagt gcgcagcgag tacgtcagac acgagatctg
47880gacgacgagg tcctcggcgt tggcggccgc cgggaacgcc agcccgtcgc ccgcgcacga
47940caggcactca atgtcaaagc acagcagctt gtagtcgggc cacgcgtcgg cctcggcgcc
48000cgcgatcggc tccaggttgt ccgcggtgca gttgacttcc acgtcgcagg aggtcgcgtg
48060ctgcgcgggc gcgcgcagcg ccacgcgcgc gcccgcgcgc ccggggcgca gccggtacca
48120gccgaagctg gtgaagcctt cgttgtccag caaaaagcgc gtcgtcacgt ccacgtggcc
48180ctcatacttg gtcacgccgg ggaggaagtt gtcgcagagg tagcccccga gccgcgcgct
48240ggccgaagac accttgtaga aaagctgcgg gcgcgtgtcg tagaagtaca cgtccgctgc
48300ctcgaccacc gcgaccgaaa ggctgtcccg cgaggcgcgg cccaggtaac cgccgggccg
48360gcgcgcgccg gcccggccgg cggcgtcctg ctgtgccgcg ccggcggcca gggccgagga
48420gcgcagcgcc gccaccatgg cgtcgatcag ctggccctcg tcgcgcaccc cgcaggctag
48480gtcgacggcg gccttctcca tgtaaaaata gtgccgcacg ccgtacacgt gcaccgccac
48540gcgcttgccg tcctccgaca tgcccagcag cgtcacgacc gtggcgccgc cgggccgggc
48600ctcggcggca aagcgggacg cgtcgccggc gctcgggtac tcggtcgtct ccacgatgtc
48660gtacacgtga aagcgctcaa agcgcgggtc gagcgcggcg cgctccgggg cggcgcggcc
48720cgcccacacg cttacgcggc gcggccagca gcaatggccc gcaaagtcca ggatgtcgtg
48780ctcctcgccg tcgaggtata ccttgggcgc gcgctcggcc gtgccgatgt gaacgccgcg
48840gcggcggggc gccgccgccc ccgcagcctc gtcgtccgtg ccgccgtcgg cgccgtcggc
48900gtccaggcag cgcggcgcga tgaagcggaa ggacgaggcg gcggtgcagt atgactcagc
48960cgcgcgcccg ccgccgcggc ccgccgcctc gtctgcgggc gcctcgccgg cgccatcggg
49020gatgtccggg ccttgccgcg cgggggcgcc tcggccgcgc ggcgcgaggt acgggttgaa
49080aaacccagcg cgcgggggcg cagtgccctg ttcgcagtct ctgtccatag cctggcgggc
49140gcaggcgcgc gactggaccg cccccggtgc cgtcagacgc tttaacggcc tcaccggggg
49200aggggccggc gcgaggttaa ataccagatc tgccagcggc gagccgtggt ggcgcgcagc
49260tcacggccgc gggcggcggc agccgacaag ccaacagaca gtgcgtccgg ccggcttgtc
49320ctcctcgcgc tcccgccgcg ccccgccttt tttgagttgt tgccgcgccg cgtctgccga
49380ccatggacgc ggcggccaag acggtagccc tcgcgccggg gcccgcgggc ttcgtgtacg
49440tctgcgacgc ggctcgcctg gacctcgaca agctcgcgct gctcgccgcg cggagccgcg
49500actcgccgct ggcggtgctg cccctggtgc gcgggctcac tgtggagacg gcattcgcgc
49560caaacgtcgc ggtggtcgcc ggcactaaga ctaccggcct gggtggcgcg gggctgacgg
49620ccaagctaac gcccagccac taccacccga acgtgtttgt ctttcacggc ggcgagcgcc
49680tgcgcgccag cacggccgcg ccaaacctga cgcgcgcctg cgagcaagcg cgccggcgct
49740ttggctttag cgcctttgcc ggcgcgcccg tcgacggcgc cgttgagacg acggccgagg
49800acatttgccg cgcagtaggc gcgagtcccg aaacggccct ggtcttcctc gcgacgacgg
49860aggctttcaa ggagacggtg tacatgtgca acaccttcct gcactacggg ggcgcggcgc
49920ccgtgcaagt gggcgccggc gaggcggtgc gcgtgccgct gtaccccgtg cagctgtaca
49980tgcccgacgt gaaccgcgtg aacctagagc cctttaacgc gcgccagcgg gccatcggcg
50040agcagcttgc gtatccgcgg cccttctaca acgccgcact ctgcgagctg ctgcacggct
50100acgtgctggg cccggccgcg gtggcgctgc gcgtgcgcag cttggacgcc gtggcgcgcg
50160gtgccgcgca cctagccttc gacgagagcc acgagggcgc cgtgttgccg ccggatgtgt
50220gcttcacggt ctttgaccag cccgcggggc gcggtggcgg ccgcgggtcc gcgcgcggcg
50280cggacccggg cgcggccaag gctgccgcgc cgggcggcgt agagcgccgg ctggcctcgg
50340tgatggcggc ggacacggcc gtgtcgatcg aggcggccat gagcacgagc gtgttcgacg
50400aggacgtcgc gtgcgtggac gactggccga tgctgcaggg cgcggcagac gacgcggcga
50460agctggacgc gctgggcgcg tacgtgggcc gcctagccgg gctagtgggc gccatggtgt
50520ttagctcaaa ctcggtgctg cacatgacgg aggtggacga cggcggcgcg gccgacgcca
50580aggacggcgc cgccgccggc ttccaccgct tctaccagat cgccgccccc tacgctgccg
50640ggaacccgcg ctgcgacaag gacggcaagc cgctgccgca gaccggcgcc ggtccggccg
50700tatctatcaa cggcgcgggc caggagttcg cgctggacca cctggcgctg gcgtgcgggt
50760tttgcccgca gctgctggcg cgcatgctgt tctacctgga gcgctgcgac gcgggcgcct
50820tcgccgggcg caacgacatg gacgcgctga agtatgtggc cagcacgctg gagggcgacg
50880tgccctgcgg gctgtgctcg cgcgacgacc ggcacgcgtg cgcacacacg acgctgcacc
50940ggctgcggca ccggctgccc cggtttggcg cgccaacgcg gagcccgctc ggcgtcttcg
51000ggaccatgaa cagcgcgtac agcgactgcg acgtgctggg gaactacgcg tcgtacagcg
51060cgcttcggcg cccgggcgcc gacgagaacg ccaggagcat catgcaggcc acgtaccgcg
51120cggccgtgga aaacgtgctc gcggagctgg accagcagcg gctgctggcg cacgacgccc
51180agtcggcggc gcagctcgag cgcgcgatta cggaccacgc cagctttcgc ggcgctctgg
51240ctgcgatcca aaacacggtc gagcaggcca ccgaggcgtt cgtgcgcggg ctggtcgagg
51300accgcgactt caagatgcgc gaggcgctgt acgaggccaa ccacacgctc tcgctggcgc
51360tggacccgta ctcgacggcc gtttgcccgg cgacggcctt cctgtttcgg cgctcggtgc
51420tggccgtggt gcaagatcta gcgctcagcc agtgccacgg catcttctgc gggcagccgg
51480tggacgggcg caactttcgc gcgcaattcc agcccgtgct gcggcggcgc ttcatggacc
51540tgctcaacgg cggcttcctc acgacgcgga ccgtgacggt gacgctcgcg gaggccgcgg
51600tcgcggcgcc gaaccttgcg gcggcgcaga cggagccgcc cgcgcgcgac atggacggcg
51660acatctcgaa ggtaagcctg gaggtcttca aggagatgcg cgtgaagaac cgcgtgatgt
51720tctcggcggg caacgccaac atgtcggagg ctgcgcgcgc gcgcgtgctc gggctcgcgg
51780gcgcctacca gaagcccgag agcggcggcg tgaacattct cagcgggccg ctgggcttcc
51840tggtgaagca gttccaccgc aagctttttc ccaacgggaa gccgcccggg agcccgacgc
51900ccaaccccca gtggttctgg acgctgctgc agcgcaacca aatgccggcg cggctgctct
51960ccaaggagga catcgagacg atcggcgccg tgaagcgctt ttcggacgcg tacgcggcca
52020tcaactacgt caacctcacg ccgggcaacg tggccgagct ggcgcagttt tacatggcca
52080acctggtgct gcgccactgc gaccacaagc agttctacat caacgggctc acggcgatcg
52140tggccggggc gcgacggccg cgcgaccccg cggcagtgat gcactgggtg cgccggcgca
52200tcgcggacgc gcccgacgcc gcggcggccg ccgaggaggt gctacgcgag gcggaggccc
52260gcccggaggt gtgggcgggc accttcgccg ccagcaacct cgtgcgctcg gtcatggcca
52320cgcggcccgc ggtagtgctg ggcctcagca tcagcaagta caacggcagc gcgggcaaca
52380atcgcgtctt ccaggcgggc aactggagcg gcctcaacgg gggcaagaac gtgtgccccc
52440tgctgtgctt tgacaagacg cgccgcttcg tgctcgcgtg cccgcgcgcc ggctttgtgt
52500gcgcgaccgc gggcgcgggc ggcgccaacc gggacaacac gctggtggaa gcgctccgcg
52560agattatcaa cggcagcaac ggcgcgctgg cgcagacggc cgtctacggc gccgtgctcc
52620aggcgctggg cccgcgcgtg gagcacatgg acctggacga ctgggcggcc ctggtggagg
52680acgagttctt cgcccagagc atggtggagc tgacggagcg cgcggccgcg cggcccgggg
52740gatggtcgcc ggagggcgcg gccgacatgc tgcgagagct ggagctcgag gcggcggccg
52800aggccgagcc cgcgggcggc gcctttgact tcggcgcgtg cgcgagcgcc gcgccagacg
52860cgacctacgc cttcggcggc cccgtggccg gggccgccgc cgcgcctgga gccaagcgcc
52920ccgacctgga cgagctgttt gagatgggcg tcccggacaa gcggcccgcc ctgaccattg
52980acatggtgta gcgcggcggc gacatgggcg gggctatagg tcgctcgtcg ccggcgaccc
53040cgcccgcatt ctcccgcccc ggtaacagat atatacatgc gccgtttgcc gcgaaataaa
53100aggataatat cgttgcacat tattcgtgtt tttgtctggc gcggttcgac cgaggccgcg
53160gcgtctttgg ccgtgaaggg gggggggaag ggggacgcgc aggcatggcg gagccgacag
53220cggcggccgc tgcgcgctcg ggcctcggct ccgagcctgg ccccgcgctt ggcccagacg
53280ccgagcccgg ctcagcgttc ggcggggcgg cggcccgcca gcggctgctt gccatcctcg
53340ggcaggtaca gacgtacaac ttccagctgg cgctgctcgg gcgctgcgac ccggctgtgg
53400cgcgccgcca cctcgacgcc gtcaagctga acgccctcat ggtgcgctgg ctgcggcgcc
53460gcctcggcgg ggcgctgcgc gcccaggcgc gcgtccgcct cacgccgctg acgtacgcgc
53520tggacctcgc gctggaccac gccgcagcgg aaagcgacgc gctgctggcg gccgcgggca
53580ccgcgagcgc gcctgccgag ttttttgcgc gcaccatggg gctggagggc gcgtgccgct
53640tccaccggcg cgcgcgcctg gcgctctacg gcggcgagac gatcgacatc gagatccagt
53700tcttgcacga cgtggaaaac tttttgaagc agcttaactt tgcccacttg ctcgcctcaa
53760ccgacgccgc gctcgccgcg ctgggcgacg tggatgcctt tttgcgggcc acggtggcgg
53820gcggcggggt ggcaccgccc gagctgcacg attttgcgca gccgtgtctg gtgtgcttcg
53880aggagctttg cgtcaccgcg aaccagggcg agtctgtggg ccggcggctg gcgctgtgcg
53940cctgcgacca tgtcacgcgg cagctgcgag tgcgcaccga gctatgcagc gtgggccagt
54000acctgccgca cgtgcaaggc gtgtcgcggg cgcggctggc ggcggcagcg gcggcgctgg
54060cggcgctggc ggcgccgacc gccgcggggg cgggcgggcc ccccgtcctc gcgacggccc
54120cgcccggagg cgacggcgac ggcggctctg tgcgcgaggc ggccgcctct gtgctcgacg
54180cgcaccacgt cttccgcccg gcgccgcgtt ggctctacgc ggtcagcgag ctgcagttct
54240ggatgtcctc gtcggcgcgc ggcgaggccg ccgccagcgc cgtcgccgcc ttcgccggca
54300acctagaggc gctcgccgcg cgggaggcgc agcaccggct gcaagtggcc gcggcggaga
54360tggcgctctt tggccgctcc ccggagcact ttgaccgcgc gctcgcggac aagctggcgc
54420agctggacgg cgtggactgt ctgctcgtgg gcagcgctgc ggtggcgccc gacgagcggc
54480tcgaggcgct catccgcgcg tgctacgacc accacatgtc ggcctcgctg atccggcgcc
54540tcacgcgccc ggaccagcgc aacgaggacg cgctgcgcga gctgctgcgg cgggcggccg
54600cgggcgaggc gggcgccgcc gcggttggcc tcggcggccc gggcagagac gaggggggcg
54660gggacgagcc cgaggaggag ggcgggacgg acaacgacgg cggcgccggg gccggggtgg
54720ggggcggtgg ggcggggccg tccgggggcg cagacggcgg gggcggcgcg gaggacgacg
54780gccccgcggg ctgggcggcg ctggcggcgc gcgcccgcgc cgatgccgac gtgcgccgac
54840agcgctatgc cgagcggctc tcgaagcgct cgatggacag cctcgggcgg tgcatccgcg
54900accagcggcg ggagctggaa aagaccctgc gcgtgagcgt ctacggggac gtgctgctca
54960acgtgtacgt ggcggtgcat aatgggtttt gcgcacgccg cgccttccgc gccgcgctgg
55020cgagcgcggg cacggtggtg gacaaccgcg cctcggacgc cacctttgac gcgcaccgct
55080tcatgaagga ggccctgctg cggcacgccg tcgacccggc aacgtggccc gcgttgacgc
55140accagttctt cgacctagtt aacgggccgc tctttgacgg cagcgcgcac aacttcgcgc
55200agccgccaaa caccgcgctg tactttagcg tggaaaacgt gggcctgctc ccgcacctca
55260aggaggagct ggccgcgttt atgctggcgg ccgcgggggg cgggtgggcg gtaagcgact
55320tccagcagtt tttttgcttc gcatccgcgc gggcgcgggg cgtcaccgcc gcgcagcggc
55380tcgcctggca atatatccgc gagctcgttc tggcccgcgc cgtctttgcg tccgtcttcc
55440actgcggacg cgtcccgctg ctgcgtgcgg accgaacggc gccgggcccg gacgggcggc
55500agtcgtgtcc cagcggcgtc tacctgacct acgaggagtc atggccgctc gcggcggtgc
55560tgaacgcgcc gcgggcgccg gagacggtcg gcgaggacag cgtcgtcatc tacgaccggg
55620acgtgttctc gctgctctac gcggtcctgc agcgcctggc gccggcgggg cgcgcgccgc
55680gctagccgct gccctgctat gggcgacgtg ggccctgctg ctggcggcgc ccgccgcggg
55740gcgaccggcg acaacgcccc cggcgccccc gcccgaagag gccgcgagcc cggcgccccc
55800cgcgagcccc agcccccccg gccccgacgg cgacgacgcc gccagccccg acaacagcac
55860agacgtgcgc gccgcgctcc ggctcgcgca ggcggccggg gaaaactcgc gcttcttcgt
55920gtgcccgccg ccctcgggcg ccacggtggt ccggctcgcg cccgcgcggc cgtgccctga
55980gtacgggctc gggcggaact acacggaggg catcggcgtc atttacaagg agaacatcgc
56040gccgtacacg ttcaaggcct acatttacta caaaaacgtg atcgtgacca cgacctgggc
56100gggcagcacg tacgcggcca ttacaaacca gtacacggac cgcgtgcccg tgggcatggg
56160cgagatcacg gacctggtgg acaagaagtg gcgctgcctt tcgaaagccg agtacctgcg
56220cagcgggcgc aaggtggtgg cctttgaccg cgacgacgac ccctgggagg cgccgctgaa
56280gcctgcgcgg ctgagcgcgc ccggggtgcg gggctggcac acgacggacg atgtgtacac
56340ggcgctgggc tcggcggggc tctaccgcac gggcacctct gtgaactgca tcgtggaaga
56400agtggaggcg cgctcggtgt acccgtacga ctcgttcgcg ctctcgaccg gggacattat
56460ctacatgtcg cccttttacg ggctgcgcga gggcgcgcac cgcgagcaca ccagctactc
56520gccggagcgc ttccagcaga tcgagggcta ctacaagcgc gacatggcca cgggccggcg
56580cctcaaggag ccggtctcgc ggaacttttt gcgtacacag cacgtgacgg tagcctggga
56640ctgggtgccc aagcgcaaaa acgtgtgctc gctggccaag tggcgcgagg cggacgaaat
56700gctgcgagac gagagccgcg ggaacttccg cttcacggcc cgctcgctct cggcgacctt
56760tgtgagcgac agccacacct tcgcgttgca gaatgtgccg ctgagcgact gcgtgatcga
56820agaggccgag gccgcggtcg agcgcgtcta ccgcgagcgc tacaacggca cgcacgtgct
56880gtcgggcagc ttggagacgt acctggcgcg cggcggcttt gtcgtggcct tccggccgat
56940gctcagcaac gagctggcca agctgtacct gcaggagctg gcgcgctcga acggcacgct
57000cgaggggctg ttcgccgccg cggcgcccaa gccgggcccg cggcgcgcgc gccgcgccgc
57060gccgtctgcg cccggcggcc cgggcgcggc caacgggccc gccggcgacg gcgacgccgg
57120cgggcgggtg actaccgtga gctcggccga gtttgcggcg ctgcagttca cctacgacca
57180catccaggac cacgtgaaca ccatgttcag ccgcctggcc acgtcctggt gcctgctgca
57240gaacaaggag cgcgccctgt gggccgaggc ggctaagctc aaccccagcg cggcggccag
57300cgctgcgctg gaccgccgcg ccgccgcgcg catgttgggg gacgccatgg ccgtgacgta
57360ctgccacgag ctgggcgagg ggcgcgtgtt catcgagaac tcgatgcgcg cgcccggcgg
57420cgtttgctac agccgcccgc cggtctcctt tgccttcggc aacgagagcg agccggtgga
57480gggccagctc ggcgaggaca acgagctgct gccgggccgc gagctcgtgg agccctgcac
57540cgccaaccac aagcgctact tccgctttgg cgcggactac gtgtactacg agaactacgc
57600gtacgtgcgg cgggtcccgc tcgcggagct ggaggtgatc agcacctttg tggacctaaa
57660cctcacggtt ctggaggacc gcgagttctt gccgctagaa gtgtacacgc gcgccgagct
57720cgccgacacg ggtctgctcg actacagcga gatacagcgc cgcaaccagc tgcacgagct
57780ccggttctac gacattgacc gcgtggtcaa gacggacggc aatatggcca tcatgcgagg
57840gctcgccaac ttctttcagg gcctgggcgc cgtcgggcag gcggtgggca cggtggtgct
57900gggcgccgcg ggtgccgcgc tctcgaccgt gtcgggcatc gcctcgttta ttgcgaaccc
57960gttcggcgcg ctggccacgg ggctgctggt gctcgccggg ctggtggccg ctttcctggc
58020gtaccggtac atttcccgcc tccgcagcaa ccccatgaag gcgctgtacc cgatcaccac
58080gcgcgcgctc aaggacgacg cccggggcgc aaccgccccg ggcgaggaag aggaggagtt
58140tgacgcggcc aaactggagc aggcccgcga gatgatcaag tatatgtcgc tcgtgtcagc
58200ggtcgagcgg caagagcaca aggcgaaaaa gagcaacaag ggcggcccgc tgctggcgac
58260ccggctgacg cagctcgcgc ttcggcggcg agcgccgccg gagtaccagc agcttccgat
58320ggccgacgtc gggggggcat gaggcctatg tatgggcagt tcgggtgcca ataataaatt
58380ttgcgcgaat cttatttaag tgcacaccgt gttatttgcg gctgtttgtt tttcctggag
58440gcgggacgct gcgcgcgagc tcggccggat tagggttcgg cgccacccgg gcacggcagg
58500gcgcccttta cttatgtttg gcgcgcggtg gctccggcac cggtctctgt ggccctcccc
58560ccgcctttgc gtttattgtc ccagctgtgt tcccgccttt gcgtgccccc cgcccgaccg
58620cccgaccgtc cttccccgcc cgaccgtcct tcccggcgcg cctcctcccg cgccacaaag
58680cacatttgac cccaaaagta atgcaaaata tacatttatt gtgggcgcgg ggcgcccgag
58740gtaccgcatt gtttgttgtg tccgtgtgta aacatcctcg acttgccggc cagctaagcg
58800ggccgctttg cgcgcgggct cgcctttcgc tagcgctgcc gcatcatctg ggccacgaag
58860atttccgccg ggtcgcacgc ttgcggcggt tgggcgggcg gcaggctggc catggcgctg
58920gcatccaccg tcgcggccac cccgggctcc tccggcggcc cgacagcggc ggcggccgcg
58980acggtcgctg gtgctgcagc tacggcagga acggacagcg cctgcgccgg cgcctgggcc
59040ggtgcgaggg tcggcacttg ggccgggccc gcacctaccc ggggcggggc agtgtactgc
59100tgcggcaagc acggcaaatg cgccgcgggc gggtgttgcg cagcagcgaa ggcaggaccg
59160taggggtagc cggccctcag ctggctcacc tcctgctgca gcgaggacac ggcggaggcg
59220agcttggaaa gagcgtgcga cggtggcggg tgcggcggcg gaggagagtg gtggtgaggc
59280ggcagctcgg ctggcgcgcc ctcgcccggg tagtaggcct cgtcgtcgtc gccgccgccg
59340ctccggccgc gcgggtggtc ccagttgtac cggcgccgct tggccagggg gcggcggtcg
59400agggggccgt cgtagcccga gccgtccgcg ccgtgcgctt gcacgcgtcg gccgtcggcg
59460atggcgccgg ccagggccat gatttggctc tcgagccccg gcggcgggaa accgtaccca
59520gggtgccagg gcgcggcgcc ggcggcgccg taccagcccg gcatcggggg cggagcggcg
59580gcggcagcgg cggcggccgg caaaaaatac ggagccggcg gaggcgcggc ggtcatcgct
59640gcgccccggg cctggctgac gaccaactgg ttgtactgag cagtcggcac gtacacgtag
59700tccccagccg gcagggggtg cgccgaggcc gcaccggctt ggtgcgctgc gctcatggca
59760ggcggtgggg gcggcggggg cggtgccggc ggaagctctg gctggcgtgc gcgtccgccc
59820gcgacgggaa gcgcaatgca gacgccgccc gcgaccgcgc tcttttgagc ccgctcgcgc
59880ccgcccgtgc gctctggccc ctcccccccg gtcggcagcg ggaacaccgc gctcgcctgc
59940aggtacgtgt ggcccgcgat gcccgcctcg cggcggcgac gcgagacggt gtcccacttg
60000tcccggacga gcatgttgtt cacggcggtc gagagcagcg tttgcgccag cgcctcgcgg
60060ggcaccggcc aggcgcggtc gccgagggcc gcgcgcgcgg cctccgcgtt ggcgaggagg
60120gcggcgcgcg cgcgcggcga gagccggcgg aagggcgcca cgcaagcgtc cggcgtggcg
60180tcgtacgtga cgatggtccc gacgcggcgg cctagcacgc acagcgcgac gtgggcaaag
60240agcgtgccgt cggcctcttc gtcgggcgcg aggcggcgcg aagagagcga cacggagggc
60300aagtagttgc tgacgaggta caggaagcgc tcgcgcggcg tgagcgaggg ggcgtcggcg
60360ccgaagaacg cggggtgcgc cacgcccgcg agcgtgtcgg ccagttgcgg gcagttgatg
60420acgccgacga aaaacagccc ggcgtcgtcg tcggcgaggg ctagcacggc gccgacttcg
60480caggcgcttg cgtggtcaat gttgatcggc agcggggcgg cgggcggcag cgcgcgcgcc
60540acctgctcgc gcgtgaggac gagctctcct tcgtcgccca tgccgtagag ggcaaggtac
60600ccgcccacat agacgggcat gctcgcgcgc gcaagcgccg aaggctcggc gtccacgcgc
60660gcgtcggcgc tgcccccgtc gggcgcgtcc gccatggcgc cgccgctttg tgcgcgcgcg
60720ggccggcggg cctttttatg gccgcggcac cgctcacacc gcggaggtga acagcggcac
60780gaagcccaga cacaaaaagt acagcaagtc gtagtcgctg gcgacgttaa actgactcaa
60840gcgccgcgtc tcgtccagcg cgcggcgcag gcgcggctgc tgcatcaaca cgcccagccc
60900ccgctcgtac tgcagcgcca cggcgtcgtg cgccgccacg acctccacga cgggcgcggg
60960cgcggcgcgg tggcggtttt ccagctccag cgccacgagg cgcagcagcc caccttggtg
61020gcgcccgcca gacacactga tggcgcgagg ggcgcccgcg gcgctgcgcg gcgccagggc
61080gtccagcgcg agggcggccg cgcccgggaa gagttgcgtg acctccacct cggggcaggc
61140ttcgtacacg cgagccacat agcgcgcgca gaggaacgtc aggttggcgt ccccgctgcg
61200cgcgcccacg gcgccgtcga ggccgccatc ggcgccgcgc gtcacatccc cgggcgcggc
61260cgccccgggc accagcgtgc caatctggaa gttgttccgg agcttgtcgg cgtacacgtt
61320gccgttccac agcaggcggc gcaccaggag caaggcggtg atagtgtcga ccgtagcgcg
61380cagcaagctc tggtcctcgg cgaggaaaag gttttgcgcg cgcgccaggt acgcgccggc
61440tgcgcggtga acgtcgtcca cgtacgcaac gccgtccgcg tccgcggcgc gcgcgggcgc
61500cgcgccgccg cctagcgcgc caggaatcgc cggcaggacg cgcagccgct gcagcgcggc
61560gaccacggcg tgcgcttcca gcgccccgcg ctcgtagcgg cccgcgccgc cgcccggcgc
61620ttggaactgc cctcgcggga ggcgctcgag gtcaaacgcg tactgcacgc gccgggccgc
61680gccttcatcg atggcgcggg ccagggcgtc caggtacgcc gggatctgct ccacgaggcc
61740gacaaaggtc acggggctct gcgagccgcc ggcaacggca cggtgcgcga ggtgcagaca
61800cagcaccgcg cactcaaagg ccgagtacgc gcggttgccc acgtacatgc gcccgctgga
61860ctgcagcgcc gccaccgcgg ccgccatgaa ggttcgagac atgcgcccat cgcggtagtc
61920catgccgcgc gtcgccagag ggcgctcggc aatcagccga tcctgcaacg tgcgatacca
61980ggtcccgaag acaatgcccg ccgacccccc gccggcacgc gcggtgtaca ccattgccaa
62040caggtcggcg gccagggtgg tgtcgtactc caggggcggg tcgttttttg ctatttgcac
62100tcggcgtgcg cgcacggcct cgagcgcgcc cgcgccgccg cccccctcct ccgcgtcagc
62160ggcggcgcgg cccgcgcggg ccgactccgc cgccgcgtcc gcctcctccg cccggcgcgc
62220cgcctcctcc aggtccgcga gcacggcggc tacctccgcc acccgggcct caatgggccg
62280gatgcgcgcg tcgacttccg cgcccgcggc gcgttgcttc gccagcaggt tgtccgcggc
62340cgctgccgcg gcctggttcc gcgcccgcgc tgcggccagc tcccgcgcgg gcgcgtccgc
62400gtccccaatc cgcgcgaaga cgggctcgtc ccagaagcgc agcggaaagg ccggcgctat
62460aaaatttcgc tcgtccggta caaagacgcg gtccgcgact gcgtggatgt ccacgcccag
62520gcaagcaaac tctaaacgcc cgagcgccat ggccccgatg ccgccacaaa gagcgccgaa
62580atttcgccca ggcacgccgc gccgcccgac gcgtctttag cgcacccgcc ggcgctgttg
62640cccgcgtgcc tgctgccgcc caccgggcgg ccgctctccc cggcctcagc agggccgggg
62700tcgccggcgg gcggccgcgg ggtggcggcc acagccgccc ttttgcccgt agccagggga
62760agcggctgcc ccttctgccg ccgcggccgc ggttgctcgg ctttgcgttt gccccgcggc
62820gatcgccccg ctcgccgcga acgcgcgcgc gcgaatgggg cgtactcggc gagcccggct
62880attatagcct caaggcgcgc cgcgttgcta gcgatcgtct gggccggcag gcgcgtcact
62940ctgagcacgc gcatgccccg ctgggagacg aacaccagca ccggcgctag gaccaccggg
63000tctgggcccg ggggggcgag atcgcgcaca agccgggccg agtcgcgcag ctgccgcagc
63060cccccgaggc gctggtccat cttgctgggc gtgttcatgt tcgttgaaaa acggcacgtc
63120ttcagctcca cgataagaca gacggcccgg gcgtgccctg cctccgcgac ccggagtagg
63180cacacgcaat cgggccgccg gctttgcagg tttacctcaa agctcagaga cacgcccacg
63240acctgcttaa aaacctccgg ggcgccaaac ttgcccaaaa gctgggcgag gcgcgggcgc
63300agcttctgcg cgccaaccgc cgcgcgtgcg tcgcaagcca gcgcctcgta aaagcggctg
63360tggcaccgga tcccggcgcg caggcgcgca cgtcggtcgc ggtcgcgcgc catggccgag
63420cccgcgcgcg ctctccgcgt cgtgcgtatc tacctggacg gcgcgcacgg gctgggaaag
63480acaacaacgg gccgcgcgct cgcggccgct tccaccgctg gggagggcgt gctctttttc
63540ccggagccga tggcgtactg gcgcacgatg tttggtacgg acgccttaag tgggatcctc
63600gcggcgtctg cgcgatgcgc cgcagcctcg cacgggagcg cacgcggcgc cggcgggccg
63660gcgcaccgcg cagacgcgga cgcggcgggc ctggttgcgt actaccaggc caggttcgcg
63720gccccgtact taattttgca cgcgcgcgtg tccgcgctgc tggcgccgcc tgggccggcg
63780ccgggcggca ctgtgaccct cgtgttcgac cgccaccccg tggccgcgtg cctctgctac
63840cccttcgccc gctactgcct ccgcgagatc aacgcggaag atctgctcat gctcgcggcc
63900gccatgcccc cggaagcgcc cggggccaac ctcgtcgtgt gcaccctccc cccggccgag
63960caacagcgcc gcctggcggc gcgggccagg cccggagacc gcgcggacgc gggctttctg
64020gtcgctgtgc gcaatgctta tgcgctcctg gtgaacacgt gcgctttcct gcgcgcgggg
64080ggcgcatggc gcgacggctg ggacgcgctg gagtgggcgg acgcaaatgc attggccgcg
64140ctcgcagacc ccagttgtga tgaatgcaaa atggcgccgg cgccggcgct gcgcgacacc
64200ctgttcgcgg cgctcaagtg ccgcgagctc tacccgggcg gcgggacggg cttgcccgcg
64260gttcacgcct gggcgctgga cgccctggcc ggccgcctcg ccgccctcga ggtgttcgtg
64320ctggacgtgt ccgcggcgcc agacgcgtgc gcggccgccg tactggacat gcggcccgcc
64380atgcaggccg cttgcgcgga cggggcggcg ggcgcgacgc tggcgaccct ggcgcgtcag
64440ttcgcgctag agatggcggg ggaggccacg gcgggcccta ggggactata aagctgcccc
64500tgcgctcgct cgctcgctgc atttgcgccc cgatcgcctt acggggactc ggcgctcggc
64560ggatcccctc ccggccccgc cgcgaagcga gccgccagac aaaaaaatgc ggcgcccgct
64620ctgcgcggcg ctattggcag cggctgtcct cgcgctcgcc gcgggcgccc ccgccgccgc
64680ccgcggcggc gcggggggcc gaagcaggga gcacagagac gcccgatacg aaatcgaaga
64740gtgggaaatg gtggtcggag ccgggccggc cgtgcacacg ttcaccatcc gctgcctcgg
64800gccgcggggc attgagcgcg tggcccacat tgcaaacctc agccggctgc tggacgggta
64860catagcggtc cacgttgacg ttgcgcgcac ctctggcctg cgggacacca tgtttttcct
64920gccgcgcgcg gccgtcgaca acgcttcggc cgctgacatt ccggacaccc cggccgtaca
64980gtcgcacccg gggctcttcg gggcggcctt ttcctggagc tacttgcaaa cgcgccacct
65040cgtagactac gacctggtgc cgagccgccc cctgcaggac tggtactttt cgcaggcgcg
65100cgccgagagc aacgccgcgc gcccgccgcc cgccccgcgc gtcacaccaa cgccggcggg
65160gcgggtggcc gcttttgaca tcaacgacgt gctggccagc ggcccggagc acttctttgt
65220gcctgtgcga gcggaccgca agcggcgcga gcgccacgtg gcggattttg ccgcggtgtg
65280gcccgtgtcc tacatccccg caggacgggc agtgctaagc tgcgagcgag ccgcggctcg
65340gctggcggtg gggctcggct tcctgagcgt ctcggtgacg tcgcgggacc tcctgcctct
65400ggagtttatg gtcgcgcccg cggacgccaa cgtgcgcatg attaccgcct ttaacggggg
65460cggcgctttt ccgccacccg ggcccgcggc cggtccgcag cggcgggcct acgtaatcgg
65520ctacgggaac tcgcggctgg acagccatat gtatctgacc atgcgcgagg tggcgtcgta
65580cgcgaacgag cccgctgact ttcgcgcgca cttgaccgcc gcgcaccggg aggctttttt
65640gatgctccgg gaggcggcag ccgcgcgccg cggaccgagc gccggccccg cgcccaacgc
65700tgcctaccac gcgtaccggg tcgcggcgcg gctgggactc gcgctctccg cgctcaccga
65760gggggcgctc gcggacggct acgtgctcgc ggaggagcta gtcgaccttg actaccacct
65820caagctgctg tcgcgcgtgc tgctcggcgc agggcttggc tgcgccgcca acggccgcgt
65880gcgcgcccgc accatcgcgc agctggccgt gccccgcgag ctacgcccgg acgcgttcat
65940cccagagccc gccggggcgg cgctcgagag cgtggtggcc cgcgggcgca agctgcgcgc
66000cgtgtacgct ttttcgggtc cggacgctcc gctagctgcg cggctgctgg cccacggcgt
66060ggtgtcggac ctctacgacg ccttcctgcg cggcgagctg acgtgggggc cgcccatgcg
66120ccacgcgctt tttttcgccg tcgcggcgtc ggcgttcccc gcggacgccc aggcgctgga
66180gctcgcgcgg gacgtgacgc gcaagtgcac ggctatgtgc accgccgggc acgccacggc
66240ggccgcgctg gacctggagg aggtatacgc gcacgtcggc ggcggcgccg ggggcgacgc
66300gggctttgag ctgctggatg ccttctcgcc gtgcatggcc tctttccgcc tggacttgct
66360cgaggaggcg cacgtgctgg acgtgctctc ggccgtgccc gcgcgggccg cgctggacgc
66420ctggctggag gcgcagcccg cggccgccgc gccgaacctc agcgcggcgg cgctcggcat
66480gctgggccgg ggaggcctct tcggcccggc gcacgccgcc gcgctcgcgc ccgagctctt
66540cgcggcgccc tgcggcgggt ggggcgcggg cgccgccgtg gcgatcgtcc ccgtggcgcc
66600gaacgctagc tatgtcatca cgcgcgcaca tccgcggcgc gggctgacgt acaccctcca
66660gggaattgac gtcgctaacc ccctgctggt gacttttgtg cgcggcacgt cgtgcgtgtc
66720ggccagcggc gcggtggagg cgcgccgcct tgcggtcccc ggcccgctgg acgcgtgcgc
66780ctactgcggc agcgtgttcg tgcgatactt gccctcgggc gcggttatgg acatcgtgct
66840cattgcggac aagcgcaccg aggttgagtt ctcgcgcggc gccaactcta gcatgcccgt
66900cttcaaccct cgcctccaca gcgggcgctc ccgcgccatg ctgctgttcc ccaacgggac
66960ggtcgtaagc gtcctggcct tcgccgggca cgaagcgccg acgttttcgc cggcgtacgt
67020ctgggcgtcg gtaggcgggg cgctggtcgc gggtaccacg atatacgcca tcgcgaagat
67080gctgtgcagc tcggtcccgc tcgcgcgcgg gtactcgtcg gtcccggtgt tttagcgcgc
67140gcgttgccct cccccccttc ccccttttca cgtctccccg ccaataaaga cgcctccaac
67200aaatctcaca cgcgcgcccg gttttggttt tttgtaaggg tatattattg attgccgcgt
67260cgccgccctt gtggcacgct gagcctaggg ttcagtgccg gctccagctt ccccttctcc
67320ctccccttcg ccgtcgctgt tgccgtcctc atactcactg tccgacggcg gcgtaatacc
67380ggccgcccca agccgccggt cgacaagggc gcgcaggtag cacacgccgt gccgagcggc
67440gggcgcgcgg tcgaacgccg tgagctgctc cgcctccatg agggttacgt ggggtgccgc
67500cgttcccagc gcgtgcgcga gcgcgcgcgc cagcgccggc agcccgccgc cggcgtatag
67560gtgcagcagc atcgcgcgga cgtggccctc ggctctccgt agctcgtccg cgctgcccgt
67620ctccacaatg cgccggcgcg tgtgccgaga ggccaggctc aagacggcgg tcatctcgag
67680gtccagcgcg cgcgcggcgg ccgcggcgtc gtcgcagtca cagtcgtaat cgtagccgcc
67740gccgtctccg ccggcgccgc ctttttccgc aggcgcgggc ggttctccca gatcggcgcg
67800ggccaaagcc tcggcgaacc gccccagtac gcacagctct cggaggatgt cgttggccgc
67860gtccgcgacc gtgccctcgt cgaggggcgc ggcggcgcgg tgcggataat tggcggcata
67920gctctcggcg aggtgctcga gcgcgccgta gcagctggcc atgccccagc gcgacagcaa
67980gaactggcac agtgcgaagc gctggcagaa gctgaacccg tagtccgcca cggattcgcc
68040gacaaagccg cggcgtccgc gcggcccaaa aagggccgtc gccgcggcca ccaagtcccc
68100gcgcgcctcg tttagcgttt cgtcgatgcc ggcccagtgg tcgctcttca ggacgacggc
68160gtccgcgcag cgcacgacgg cacacagccg cggcaggggg tcgccgccgc agagcggggg
68220gcctgtcatg gcccaggcat tgtaggtccg cgggatgagc cgcacctgca caaagctcga
68280cacggcggcc tcgcggcgcg cctgcggcgc gcggcgaacg cccgcggcgc gagcggtggt
68340gacgatgact tcggtggtcg cgggcgagcg cgcgtctgcc ccttctccgg cgccgccgcc
68400gcagcccgcc tctgcagcga cgcgctcaaa aagcccgcac agtagggggc gcacgggcgc
68460cggcggggcc ggcaagcacg cttgcatcag cgcgaagcac tcccggttgg gcgcgtacac
68520gaagcccgag agcgcgttgg tgatcgtggg cacgtcaaac aggtgcagaa cgcgccgctc
68580ggcgtcgtgg tagccggtcg tgagcacgag ccccgaagcg acgccgagcg acacgaagca
68640ctcggccagg taagggtcgc caaccggcac gtcgaagcgg ccgcagaggt ccgcgcccgc
68700ggccggggcc ccgccgcgcg ggcgcaagcg cgccaggcag tccacaaacg cgcccccgcc
68760gtcgggatcg tcctcgccgt cggttgcgcc agaaggggcg aggggaaccg cgcgcgcgag
68820ttccgcgcgc acgtagttgg ctacggcgcg gtcgctgcgc ccccagccgc gcagctccag
68880cccaaacttc accgcctccc cgcccctgcg ggcgactgag actaccgtgc ccgcatagac
68940aaagtacgcg acgtcccccg cggccgagac gtagaaggaa accccgttgt gcgcgacgac
69000gctgtggtag gcgagctcca tcgccgcggc ggccgcgcga gcgggccgac ggggggaaca
69060atgacgcaaa agggccccgg gcgctgagtt aaatgcggcg cctactcgcg ccgcccggga
69120gtcgccgcga gcatgctcgg cccggagagt gcagcccttt tgcgcgcgcc cgagccgccg
69180ctgggcggcg ccgatgcgga agagggggcg gccggcgcca gcccgggaga cagcggctcg
69240gacgacgagg aggatgagct gctgcggtgc gtcgcgctgt cggcgtacgg gggcgacgtg
69300gactttctaa cgcgctcgcc gcgtctggcg ccgcgcgcgg acgggcgggc cgcgttctcg
69360gcgtacgtgg tctttggcgc ggcgtccgcc ttcgggctga atcccgcctg ctgcctgctg
69420ttcttatact actaccggac gtttggcgac gcgacgtttg ccgtcgccgg cgccgcggca
69480acgctggcct actacgcgcg gctggcggcg gccgcgggct tcctctacgc gggcgtgcgg
69540gcggaccggc tgccttttgg gcgcgggcct cgggcgctgc tggcggcgct ggtgctggcg
69600cgcgcggcgg tctttgcggc ggtggcgctg ccggcggcct ttgcgggccc ggcgctgttc
69660ctgcggctca gcgcggcggt ggcggacggc ggcgcgcgcg cggcggcggc ggggctcctg
69720ctggccgggc tggcggcgta cacggcggat ctcgtttgtg acgtcatcgg gtttttcgcg
69780ccccgggcgt ggatgcgcgt gtgcctgggg ggccacgtgg ccgtgtgacg ccaccgcgtg
69840agtataaaac gagcggcgcg gccgggcggc cgcactgcgc gcgccgcccc acaccgcgcc
69900atggaccgcc agagcgagcc tccgcgcgcg cccgcctaca cgggcgggct ggtctccggt
69960caagtgctgt cgaacatcga agtggcctgc caccgcgcgc tgttcagctt tttccagcag
70020gtgcgatcgg acgacaacgg cctgtacgcg gccgcctttg acgccctctt gggcacgtac
70080tgcaacacgc tgacactagt gcgctttctg gagctcgggc tctcggtggc gtgcgtgtgc
70140accaagttcc cggagctgaa ctacgtgcac gagggcacga tccaatttga ggtgcagcag
70200cccatgatcg cgcgcgatgg gccacatccg gtggaccagc ccgtgcataa ctacatggtg
70260aagcggatta accggcgctc gctgagcgcg gccttctcga tcgccgccga agcgctggga
70320ctgctcgcgg aggaggcgtc cgacgggacg caggtttcgt cggccatgcg catgcgcgcc
70380atccagcagc tcgcgcgcaa cgtgcagacg gtgctggatt cgttcgagcg cggcacggcg
70440gaccagctgc tgcgcgtgct gctggagaag gcgccgccga tgtcgctgct ggtgccgctc
70500tcgctgtacc gcgaggacgc gcgcctggcg gggtcggcgg cgcgcgccgc gctggtctcg
70560gagctgaagc gccgcgtgcg cgacgacgcc ttcttcttga acaagagcga gggggcgccg
70620gggcgcgagc tcgcgctggc caagattacg gacctcgtgg gctgcacggc cgcgtcggtg
70680gcggtgccgc gcctgacgca ctgcgacagc cgcgggcgcc cggtggatgg cgtgctggtg
70740acgacggcgg gcatcaagca gcggctgctg ggcggcgtgc tggcgctggc cgactcggag
70800gcggacgtgc ccgtgacgta cggcgagttc gtgatctcgg ggctgaactt ggtgacggcg
70860ctaacgatgg gcaaggcgct gcgcgggctg gatgacgtgg ccgcgcatct gctggggctg
70920gaggggaccg cgggcccggg gctggccgtg gccgccgact acgacgcgcc ggcagaggcg
70980cgcgtaaagg cggacctggt ggccgttggg gaccggctag tgtttttgga ggccctagag
71040aagcgcgtgt accaggccac gcgggtgccc tacccgctgg taggcaacat ggacctgacg
71100tttgtcatgc cgctggggct gtacaaaccg cctgcggacc gctactcgcg gcactcgggc
71160agcttcgcgc cgccgcccgg gcaccccgac ccgcgcatgt tcccgccgcg gtcggtgttt
71220tttttcaaca aggacggcgc gctgacggag gtttcgttcg gcgcggccat gggcacgctc
71280tgtcacccgt cctttctgga cgtggacccg gtgctggcgg cgctgcgcgc cggcgcgcgc
71340cagaggcgag aggcggagtg gtgcctcttc ggcgcgtacg tcgccgaccc cggcgagcag
71400gagctcgcgg accaggtgcg gcacttcctg gacgcctggc acgcgctgct gcccgcgcgg
71460ccgcgctggg tgatggagtg tgccatgacg ccggaacaga tggtggcgcc cggcaaccca
71520aacatgccgc tcgagctgca cccggcgttt gacttctttt tggggcccgc ggacgtggag
71580ctgccagggc cacccaaccc accacaggtg atgccggcca tgcaggcgat gccccgtatc
71640atcaacggca acatcccggt gccgctgtgt ccggtggact ttcgcgacgg gcgcggcttt
71700gagctgagcg tggaccggca ccggctgagc ccggcaacgg tggcggcggt gcgcggtgcc
71760tttcgggacc cgaactaccc catggccttc tacatcattg aggcggtcat ccacggcagc
71820gagcgcacct tttgcgcgct ggcgcggctg gtgatgcaat gcgtgaccag ctactggcgc
71880aactcgcgct gcgccgcctt tgtgaacagc ttccccatgg tgatgtacat caacgcgtac
71940ctgggcaacg gcgagctgcc cgaggactgc acggcggtct acaaggacct gctggagcac
72000ttgcacgcgc tgcggcggct cgtggacgag tacacagtgc cgcacgcgcc cctgggcggc
72060gagcaggagc acgccgcgct gaaccacgcg ctgctggacc cggtgcttcc gccgccgctc
72120atctgggact gcgacgcggt gatggcgctg cagcgcgcgg acccggcgcg cggcgcgcgc
72180gcacgcgtaa acggcgccgc gccgcacgtc gtggcgcggc gcgagctggc cgaagccaac
72240ttccgcaacg tcgggcccga cctggtgcac aaccgacccg tgcgcggcgg cggccccggg
72300gcgtacccgg tcccgcacca tggcgacgag tggctggtgc tggctaagat cttctactac
72360gccgtggtcc cggccttcgc gcgcggcgcg tgctgcagca tgggcgtgca ctacgaccgc
72420gtgtacccgc tggtgcagtc ggtcgtggtg ccggatctgc cccccgacga ggagccgccc
72480gcgggccccg agcacccgcg ccacccgctg cacccgacga acctggtggc caactccttc
72540aacgtgctgc tgcacaacgc gcgcgtggcg gtggacgcgg acgcgctgct ggtgctgcag
72600gaagccgtga ccaacatggc cgagcgcacc tcggtggtgg tggtggacgc gggccccgac
72660gcggggacgg ccacggccgc aacgcggaac atgcgcacgc tggacgcggc gctgcaccac
72720ggcgtgctga tgatggcgta ccagcggaac gacgaaacgc tgctggacgg ggccttcttc
72780tacccggcgc ccgtgcacgc gctctttgcc tgcccggacc acctgcacgc gatgcgcggg
72840ctgggccaaa acgcgctgct ggccgcgcgg cacgtgccgc ccgtgccgca ctttgtgggc
72900gccaactact acgccaccgt gcggcagcct gtggcacacc acgcggcgca gagccgcgcc
72960gacgaaaaca cgctcaccta cgcgctgatg ggcggatact tcaagctgag tccgctggcg
73020ctgacgcacc agctgcgcac ggggctgcac cccggcttcg ggctcacggt cgtgcgacaa
73080gaccgcttcg ccacggagaa catgctcttt gcggagaaag cttcagagtc gtactttgtc
73140gggcagctgc aggtggcgcg ccacgaggcg gtcggcggcg tcgggtttac gctcacgcag
73200ccgcgcgcgc acgtggacct cggcgtgggc tacacggcgg cctacgccgc cgcggccatg
73260cgcacgccgc tcacagacct gggcaacacg ccgcagaacc tgtacatgac gcgcggcgac
73320ccgcccatgg tgaacgggga cgcggacggc ttcgtgcgcg acagcgtcaa cgccgggagc
73380cgcatccggc cgcagggccc cgcgccgctc ttcgggccca ttatgcccgc cgcgccggcg
73440ggcacggcgc gcgggcaggc tgcggtctgc gagttcatcg cgacgcctgt ctcggcggac
73500ctcgcgtact tccgctcgcc gtgcaacccc cgcgggcgct cggcaggcgc ggcctacgcc
73560ggcgacggcg agtcggacgc cgacgacctc atgttcgacc atggccaggg cgacccggcc
73620cacccgcacc gcgccaccgt taacccgtgg gcctcgcagc gacactcgta cggcgaccgg
73680ctctacaacg ggcagtacaa catgagcggc gcctcgccgg tgtacagccc ctgcttcaag
73740ttcttcacgc cggcggaggt gtcggccaag gaccgctgca tgagccggct gattgcggag
73800gtgggcgcgg gcgtgtcgcg gagcacgtcg gacacggagc tgcagttcaa gcagcccccc
73860ggcaccgggg agctcgtaga agacccgtgc gcgctgtttc aggaggcgta cccgccgctg
73920tgcgccagcg acgcggcgct gctgcgcgac cgcctcgccg cgcccggcgg cgcggccgcg
73980ggcgtcgagg gccggctgga ggagggccac tttgcgcagt acctgatccg cgacgcctcg
74040ccggtgcggg gctgcctgcc ggtgggctag gcgcgcccgc cccgccccgc gcacccgcgc
74100ataaaaacgc cgccgcggtg cgcggggcgc gtcagttccg ccggcgcccc gcgcagcgat
74160ggcccagccc gaagcgttcg aggtggagat tgtgctcccc ggagacctct ctcacggcga
74220cctagccgcc ctccagaagt gcgagggcaa ggtggtattc tttaccacgc tgcgccggcg
74280cgtgccgctg gcggacgtgg cgctggcctc cttctcggtc aacggcgtcg cgccagacac
74340cctggggctg atggccgcgt accgctgccg gttcccggcc gtggtgctgc gcgtggcgcc
74400ggggcgaatg atggcggcgc ctctcggcgt ggggcccatg ccgcgcggcg ccttcctgca
74460aaacacgggc ccctttgacc tctgcaacgg ggacgcggta tgcctgctgc cgccgctgct
74520ggggcccggc gaccggctcg cgctggcctc ggcgggcgcg gagctgctgt ttcccatgac
74580ggtgccgctg ccgcaggcgc gcgagctggt ggcgcgcgtg gtggcgcgcg cggtagaggc
74640gctgggggac cgcgcggccg ccgcgcgccc gcgggccgcc gacgtaatgt accacaacgg
74700gcgccgctac caggtgacgc cggacgtgct gtgccgcgag ggcgcggacg cggccgcgcg
74760caccctcgtg ctgaacatgg tcttcaacgt caacgagggg agcttgctgc tgctgtcgct
74820gatccccaac ctgctgacgc agggcctgca ggacggcgtg gccaacgcca tcgtgcagct
74880gggcagcgcc tcgcgcgagg cggggcagct gctgcgcctg gagccggccg agccgcggca
74940ggacggcggc cggcgctttt gcctgtacgg ggcgctggcg gcctggatta gctcggcgac
75000ccggctggga gacgcggtcg gcgcgcgccc cctggcgaag gtgtgcacgt tcgacgggcc
75060ctcggtagtg cgtgtgggcg aaaaggcgcc catcgtggtg ccgctttagg ggcggctgtg
75120gtggcggctc ccctcccccc tcaccggtgt taatacgcac gacaataaat gagctgacac
75180acgctcgcac atacacagtt tgtttgccgt ttatttgttt attggggaca gcgacggggc
75240ggggcgccag gctcagtccg ccggcgggcg gggggccagc gggcagaagg cgccgtcggt
75300gggcgggagg ctgcccacga acacggccat cactagcgcc accattagat cgtcggcggc
75360gccccggcgc ttgcccgaga aggcccgggc cccgccgggg ccggcggtgc tctcggttag
75420gttttgcagt tgctcaaaga ggtactccac ggggtctgtc tgcaggcgca cggtcagcga
75480ggccaggtcc tgggaggcaa ccacgcgccc ggagttgaat aagcggatga agtggtcaaa
75540ggcggccgtc ttctgcttct gcagcaaaaa aaaggggtag gccaccgcgc tcccgggcgg
75600gcggcagtgg taaaagcgcg tctcggcggg catgggcacg gcaccggacg cggccagcga
75660gtcgagctcg cgccggacgc cgagcgcgat cgcgaccgcg gagtcctggc tgctgttgcc
75720ctcgacggcg acaaagaggc cgtcgaggcg gcgccggtgc acggccatga cctgcgcgaa
75780gcagcgcacg gcgcaccgcg cgatctcggc ggccgagctg cccgtgagcg ccggcaaaaa
75840aaagtgctcc aggcccagca ccagccagct gccgcgatgc cgccccacga cggcgatgcc
75900ggagccggag gcgcgggcgt tgctcgtgaa ggccgggtcg atgtacatgt agagccgctc
75960gggccacggg ccgcgggccg ccgccgtgga tggccgatag agcagaaact gctcgcccgc
76020cgcgcgggtg aacacggccg cgggctcggc gcggcgcgcg acctcgccgc cgccaatgat
76080ctcctgcatg aacgagttgg gcaggaaggt ctcggcggtg ttgcgcgcgg cggcgtccat
76140ggtgatgaag acgggcttgt tgaggacgta acacgagcac gcggtggcgc cgccgtgcgc
76200cgccacacgc ggcgtgtgct cgttgcatat atacgtcacc acgttgagca gcccgtcaga
76260ggcgcccttg aggttgtaga ggaagctcgt gctggccttg ccggtgttgg tcgaggagac
76320gaagattatc ttgcagctgg cctggttcag gaacccgact atcgtctgga cggcctcggg
76380gcggataaag ttggcctcgt ccacgaagag gaggttgaag tcttgcccgc ggatgccctg
76440cgagacgcaa ataatagaaa aagaggcgtg agcagcgcgc gtgccgacct cgtcccgacc
76500cgacgccatg gaggcgcacc tcgccaacga gactaagcac tgcctggcgc gcggacgcag
76560cgccgcgggc accgtcgtcc acctaatcat atcgagcgac tgcctacggg ccgccggggc
76620ggaccccggt cgcctcttca cggcctcggg gggggcgccg ggggccgcgg cgggggcacc
76680ccgcggcggg agcgcgcgcg cggacttttc cgccgcggca cagacgcgct tccacggcag
76740cggcgcctgc agcgcctggg agcccgtgtt cgcggcctac gtccccgcgg gcgcgctggc
76800cagcgtgtta ctgcccacgc agccggcggc ccggcccccg atcttcgccg ccgctggcgg
76860cggcgaagac cgcggcggcc tcttcgtgtc cctgcccgtc gccctgcccg agggcgggga
76920gggcgccttt ttcgacccgt tcacgcgcgc ggcgctgcgg ctggaaatgg ccgacggcga
76980gctcgtcgac ttgctcttcg cctacgaaga gctgctgccc gccggcaccc gctacgaggc
77040cgacgtcccg cgcctggccg ccctctgctg gcagtttgtg cactatacgc ggcgccatgc
77100cggcctgccg gccgccgccg tcgccgcggc cgagcacatg gaggcctgcc tgacggaggg
77160cggtcgcgcg ccgccgctgc cgcccggcgg gcagatccgc ccggagcgcc tgctggccga
77220aggcggcttt gacgaccccg ccgcggtcgc ccgcctcgag gacagcgacc aggaggtcct
77280ggcgctcatc cgccgcgccg cagaagtagt agcggcgcgg cacccgctgc ggcgcgcgcg
77340cgcgccaatc ggcggcccgc gcgcggtagc ggcggggctg cttcaaggcg cgcgcgcgac
77400cgccgccgcc tgcgccgcca ccgcgccggt cctgcctccc gacgccgcga ccgcgctgct
77460gcccgcgacg gagccgcggg ccgccgggcc cggacttggc gcggtcgcgc gggcgctggc
77520gggcgacacc ctcgtggcga cggcggcgac ccgacaggcc cgcacactga ccgagtggtt
77580cgacgcgggg cactgcgcgc tgctgggcgg cgacacgccg tgcgacgcgt ggcgccggcg
77640cccgctctcg ctcgtggccc ggcggcacta cgagacgggc gagggcttcg tcgtcgtggc
77700gtacgagcag tcggcgggct ggggcgggcg ccgggcgccc ggcccggccc gccggcccga
77760gtcggtggcc ggggagctcg cgcgtgcctg cgagcgcgag ggcgtggcgc accctcgtgc
77820gctttccgcg gccgcgcggg ccgagctcgc acggcggcac ccgtttctgg cggcgccgct
77880gggcgaggac ggcgcgccgc ccgtggaggc cttcgacgcg ggcgccgagg tactgctggc
77940cgagcgcttc aaggcggcgt gcgcgcgcgc gctggtgcgc gcgcttgcgc gcgcgtgcga
78000ggcccgcccg gacctacccc agcggttcca ctacgacgtg cgggaggccc agcgcggatg
78060tctggaggac gtggcgcggc gcgtgccggc ctttttgcgc gcactggcca gcgcgctggg
78120ggcgctctcg gcccgggagt ttttgaacag cgcgctctgc gcggcggcgg tggcgcacct
78180ctcggcgacg agccccggcg gccggggcgt cctgccgtat catcgcgcgt gcttttcgct
78240gctggcgggc ggcgagcgcg ccctgctgtt tgattacttc agctttggcg gggaggtcat
78300aaaggtctcg cgctcgcccc tcgcggccac gacggcgcag gagtccgggc ggcggccggg
78360ctcgatccgc ctcttggacg cgggcgccaa aagcgggcgc gcgccggcct gcggctcata
78420cgcacccggc gagtcgtacg cgtacgcgtg cgtaggcttc tcgcggcggc tgcggtgcac
78480cgtcgtgttc ccgggcgggt tcgccctgga ggccgacgtc gccgcgcacc tggactggcc
78540tgcgcgcctc tgcgaggcgg tgctcgggcg gctgggccgc cccctccccg cgcccccagg
78600cgcgccggcc ccgtgagcgc gacgaacggc gggcgggcaa gcgcggcgca tggccgagga
78660ccccgccgct gcgggcgcgc tgctggcgcg cgcgctgacg gaggagctgg gctgcctgca
78720cctcgtgcgc agcgactcgc gcgtaaagat ttacgtggcg gtggccacgc tcggccggct
78780gctcgcgcgg ctggtgtcgc cggaagacgc gagtcccggc gctgccgttc gcgtcaccct
78840ctacatcacg cggccgcgct ccctggagct gccgccgcgg cacttccacg tcctggtgct
78900ttttggcggc gcggtcgcgc gcgcctgcgt cgccggcgtg cgcacgcggg cgctggtgcc
78960gggcagcacg cgagtgcggg cggtcttccg cgacgcggtg gctgtccccg cgccggccga
79020cctccccgac ccgagcgccg aggtcgtgcc gcccgcgccc gcggagcatg tggacccctt
79080cgcctttacg gccttcgcgc gcccgccgcg cgacgccgca gactgcttcc agctggcgcc
79140gggcgtgtgg tggtcgtacg cagaccggcg cctctacctc gtgcagatgg acgaagccct
79200gctggccctg tgccccgcag gctggcgctc gcgcagcctc gggggcgtgc tcgggcggct
79260gctgagccac ccggagggct gcgcggcgtg caccgccaaa tggcacatcg acgcgcttaa
79320cgcggcgccg gagccgggcg cgtgcgacgt gtgcccgtgc gccgcgccgt gcctgtggaa
79380gaaggcccgc cgccaggacg tgcccgtcgc gggggactcg agcctgtttc gagtgctttt
79440tacggacgcg gtcgcgcggg tgcgcattct gggctcgcga cgccggccgc ggatcacggg
79500cgcgctcccc gagctgctag ccggcgtcgg gccgcgcggc gaagccgtgc cggtgaacgg
79560cgccggctgg cagctgcgcg tcatggacga cgacgtcacg cgactgctcg cgagcagctg
79620ccgcgcgatg cgaagcgtgt gcggcagcgc gcggctcgcc gtggggctga gcgcgtacta
79680ggaccgccgt gcccgctctg tcgccccctc gcgccgtttg cacgcacccc ctttttttcc
79740aaaataccaa gataccaata aacaacacac ttgttagcct atttcgcgcg tgcgcgtttt
79800ctgtgtactt acgtttgtgt tgtggctgga tgcaaacacg atcgtgctgc gggcgccgtc
79860cgggaacgaa aaggagatca cttccccctt gacgtggtct acgcgctcgc cgccgaacca
79920ctgccggagc cgcgccacga tctcctcgaa tacgggctcg gtggctttgc ggatgtgcgc
79980cgtgtatccg attttgatgc ccttgaacgt ggcgagcgcc agcgcgatca gcggcaccag
80040aaaccaggtc ttgccgtgcc gccgtggtac caggaacacc gtggcccgct gccggaagtg
80100ggcgaccgcg gcgtctgaga agtccggcgt gttgaaggcc acgcgcaaaa aggcgccaat
80160gcgctcggcg tggtccccca acagcgtcgc cgccacgaag tacgtcgcgt gcatcagaat
80220catcttttgg aaaagctcca gcgcgccccg cgtctggccg ctggggggct ctacgcgcgc
80280gcgtttggcg cggggggggt cggcgtcatc gccgccgccg aggtgcgaga acgacgtgcc
80340caccagccgg ctgaaccgcg cgacgaacgc ggccacctgc gcaaacgcgc ccgacgcgcg
80400catggactcc agcgccgcca tgacgctgtg gtacgcgttg cagtgcgccg ccgcctctgc
80460gggcgggtgc gccacgaagc gcagggcgct caagaccccc gcgagctccc gggaaacgtg
80520cgcctcgccg gtgccggtat ttaacccggc ttcggcgcgc gccatgctcg tcagtagcag
80580gcgagaggcc gtggcggcaa acagcggcgc cagctcgcag tacccgtgca gcgtgcccac
80640gcctgggacg accgtctggt ggcgcttggg ggccgcaacg gcaaagtcga ggaaggggac
80700ccgcgcgtcg tcctccccgc gggcgccgcc gccgccgtcg ggccgcgctc cccgttccgc
80760agcgcggcgc tgccgctcgc gcaacagccg ctgaaagtag cgggcggatt gctcgcccac
80820ggcgcccccg aacatcgctc gcgcgcgtca cgggcgcgac tgcgtcttcc ccgcccccgc
80880ccccgccgcg gttgccgatg gcgacggcgg cgctcgcggg agacccggcg ccggggagcc
80940gaacggctgc gcgccggcgg cggctgcggc tggaagaagc acaccggagg gaggcgatct
81000tcaagtcgcg cgtcgtggac ttggtccgcg ccggcgcgga ccgggacgac ccggccttta
81060tacacgcctt tacggcggcg aaggccgcgc gccgcgactt gggggggcag atccgggcgg
81120cggcgcgcgt cgaggccgtc cggcagcacg cccgcgacat agagacacgc gtggccgccc
81180aagcggccgt ggccgccgtg ctggccgaaa atcgccgctt tttgcgcggc gactttctgc
81240gcgcgtttga cgacgcggag gacgcgctgc tggaccagga ggagcgcatg ggcgacgccg
81300ccgcggactg cgggggcgac gtgggcgtgg gcggggcctg gctggacggg gacgacgaaa
81360gcctgctcgc ccagtggctg ctccagagcg cgccgcgcgt cggaccggac gtgttaagcg
81420acgactggcc cgccgcgccg ctcggagggc tcgcggcggc gccagccggc gcgcgcgtag
81480atgcaggctc ggcggcagcg gcggcgggcc aggctgggcc tgccgctgct ttccgggaga
81540gacggccgcc ccacagcacc ccctgacccc ccgcgccggc tcttcagcgc ccccgcctcc
81600ggcgcgccag ggggcgcaga cctcctcgcg gcggctgcgg tgctgccgcc ctcgccgcct
81660cgggccgccg gatccgcgct acgccgcgcg ccgatccgcc ccgcgagccg ccggcggcgg
81720cgctcgcgcg cgcacatctt gcggctggcg gcagttgagc ggcccgggtg cccggtcttt
81780gtcgcggacg cgagtctgcg catgccttcg gcggccgagc tcgccggccc cgcgcagctg
81840cgcggggccg gcggctacgg gagcgtcgtt gtgcacgagg ccgccggcgt ggccgtaaag
81900acctttgcga gtgccgccga cttcgagcac gagctgctcg tgacgctgct cgcgggcgag
81960tgctcgctgc gcgcgctgcg gcacgcgcgc gccgacgcca tcatccggcc gtgcgggttc
82020agcctgcggc gccggcagct agccctgccc gcgtatgacg cggacctggt ggcctacgcg
82080gaggcggcgg ggcgcgccgt cctgtcgccc gccgcactgg cggcgatcga gcgcgcgttc
82140gtcggactcg gccgcgcggt cgtgtttcta aacgcgagct gcggcctcgc gcacctggac
82200atcaagggcg gcaacatatt cgttaacacc gcgggcgcgc tcatcacgcg ggcggtgctc
82260ggagacttca gcttgatgac gctcaccgcg cagtcggcgc tggccgacgc ggagtttctc
82320gtgtcgacgg acgacggcaa cagcgacggc gcgtctgacg ccgtcgccgg agggcgcctg
82380cgtttgcgcc tgccgcccga cgcccggatg ccagaccctg aaattgttat gggccactgc
82440gcgacgcggc cctcggagat gctcctcgac ttccttaacc ggcacggcct tcgcgggcgc
82500cccgagccgc tgcccgcgga cctaggactg gccatcgacc tgtacgcgct cggccacgcc
82560ttgctggagc tggtgttaac cggcgcccgc gaaacgcccg aggtccagtg tgcgcggcgc
82620cagggcgcac tgcacatgag cgcgcgccgc gtgacctgcg ggctggtcat cggcattctg
82680gcgcaccggt gcgcgctcct ccccttggtc ttcccggcaa ccccgcgcac ggccgcgtgc
82740ggcgtgccgt gggacgagcc cgcggccgtg cgggcggcca tcggcaacgt ggcgatccgc
82800gcggccttcg accgcactac cgaagcgcac cgcgcgcggt acacggagcg cgtgcgcgaa
82860gcgctcgcgg cggcgcctgt gcgccgcgcg ctggagcttg ccgcgctctt ttgccacccg
82920aacccgcgag cgcggcgcgc cgcgctcgtg ctgtggtcat gagtcgggcg ccgctcgcga
82980agcgggcccg cttcgagctc gacagcgcgc gcgccgcgct ggagcgcttg ccggaagggc
83040ttatggagag cagcatggac gagtttctgg ccgaggcggc gggcgaaggc gacggcgacg
83100acccggtcgt ttgccgcgcg gcgtacgtcc ggcacgtgct cgcccgtgcg ggcgcgccgc
83160agccagccgc ggcgcgcggc gcccgggggc tttttctcgc tgtcgaggcc gcgacccgcg
83220gccaggccgc ctgcgatctg tggtggctgc tccggcggag cctggccacg gcctcgtcgg
83280tccgctgggg cgccgccggc ccgcggccgc tagtgcgctt gggccgcggc gcggccgaag
83340agcgcaacac ggcagccacg gccttcgggc gcgataatga gcccctggcg cgagcgctag
83400tgcgcgcctg ctgcgtcccg cccggcgacc tcccaacgcc cgacgggctg gcggacggcg
83460gggggcgcgc agacgagctt gggcccgtgt ttgtgtttga cgccgcggcc ggggcggcgg
83520ccgaaagcgc ggcgggggcg ggcgcagagg cgcacacctg cggcctcctg atcgacccgc
83580gcacgggggc gcttggcgcc tccatcgaca tgctggtctg cgaccgggac gcgcggggcg
83640agctggcgcc gcatcccacc cagaccgcgt tgggggtctt tgagattaag tgccgcgcca
83700agtacgcgtt cgaccccgac gacggcggcg cgacggcgcg cgcgtacgcc gccctgttgg
83760cggcgcgcag cgccgcggcg ctgcgtgcct tcctgcggtc cgtgcgccgc cccggggtgg
83820agcactgccc tcccgacggc tgccccggcg ccgcggaagc gctggcgagc tgcgccgacg
83880cctgggcgcc gcccccgcct gccggcgccg caccggcgcg gcgctgctcc gagtttgact
83940ggcgccacct ggcgctgaac cggagcgtga cgtcgcgcgt gtggctattt aacgagcccg
84000ccgctcactc gggcgctatt ggactcgcca cgtgggacac cggcgaggca gccctcgaag
84060cgcccctgtt cgccaacccg cggcacgcga acttcaagca gatcctcgtg cagagctacg
84120tcctcgcggg ccacttcccc gagcgcgccg cggcgctgca tctcgtcact ttcatcggcc
84180ggcagcggcg cgcccgcgag cagggcccgc tcgaagtgcg cgcggggccg ggggcggaga
84240cgtgtaccgt accgcgcgaa ggcgccgtcc ccgttctgct gatcgccacg cctgtggtgg
84300tcgacggcga gctcgcgcgc gagtcgctag agcagccggc ccgggaagcg tttcgggcgg
84360ccgtcaagga gtcatgggac aggcggcgtc gtgcagccga tgccgccgca accgcatctt
84420gacgcgcgcc ggggacctcg tagccctaga cgcggccgcc tttgaggact tcagcctcga
84480cgacctgcag gccctgacgg ccggggccgc cgcgggggag gagggcggcg aggacaaaaa
84540aaacgccgac gacgactggt ccgacgtcat caccagcgcc ccccggcgcg ggcagcgccc
84600ccccgtaaaa ccgtaccggc cgcagcgccg cgaggtgtat tgagcggccg cggacccgcg
84660gcagacccgc gacaataaac acacgcaaag aattacacga tttgatagca tctttatttg
84720acgtgcgcgg ggggtgggga gcgggggggg gggcgggggt gtgaacgcgg gagtggggga
84780cctccggtct ccttagcggt atggttggcg ggcggggcgg gcgtccgcct cgtacacggc
84840ctcctcgtcg tcagaggcga cgccgcggtc cagcagcgcc gctgcgtcgc cttcgagcgg
84900ggccatgccg cggctgctgc gcgctcgggc gatgtagcgc gccgcttgct gtcgcgcggc
84960gctcacgtgg ccgtagaagg cgctgccttt gcgccggtgg tgcaggcagg cgcgcaccaa
85020ccgcagcacg agcatggcca cggccagcag ggcgacgccg gccagcgcca gctttacgcc
85080tagcggcagc ccgggggcct gcgtgcgcac aaccccccgc agctggtgga agtagtcgtg
85140cgaggcgacc gcgatgcagc tagctgccac cagcgttcca aaggccggcc cgggcagcac
85200ttgcgtgtag cgcgacagga ctagctcggt cagtaccaaa aagagcacgg cggcgaggca
85260gaagaccgtc acgccggcga cgaccgtttg tgccagcgac agccccagcc cggcccccag
85320cagctggccg agcatcaggg gcgcggtgcc aatgatcagc gccagcaggc cgccggccag
85380gttgatcatc acggcgcgcc cggggcccag caggcggtgg gcgcgcgggc tcctctcgcg
85440gagggcgtgc acggcctgcg cgtactcggc gccgggcagc ccggcggtgc aaaagagccc
85500gacgaaggcg gcggcggcgc cagcgtgcgc gaggtaggtg gccgcggcca agaccatgat
85560cttgtgggac agcagcagca cggccgcctg cagcgtccag gccgccagcg cgcccagcag
85620cagcgcaccc gggggcgtgg caagcgtcgc cagcgcgttc atatgatacg ccgccgcaaa
85680accccctgag ttttcgcggc gaatgattat agcggccgcg acgtcaaagg cggcgacggc
85740gagcagaact acggccgtgt acgcggagaa ggccgctgtg gtcggcgtct ccaaaaacag
85800cgccgggtgg cgcgcgccga gctcccgctg cgcccaggcg ccgccgtcgg ccgagaggtt
85860ccgcgcattg taattaacta tggccgcgta gaagcagggg agccccgcgc ccggcgaagc
85920ggcgccgatc agggtgatca gcagcagcag cgccagcgcg gcgaagacgc cgacctgagc
85980gagccacaag cgccagtgca cggcggcagg ctgcgcggag cccgccatga cggcaacgcc
86040gggggcagcg gccgatgcgg tgcgcgtcga gggtgcgggc gcgtgcagcg acgggggcga
86100agaagcgcgt tatgcgtcga gcgcgtcgct ggcgcggatg ttatacggcg cggacctgag
86160cgagcgcgtt cgccggcgcc accccgccgt ttgcgtggag caccaatcag gacgccccgt
86220cgcgttgccg tccccgcttg cagcggacgc ccggcgcgtg accgtggtcc gcgcgccgat
86280gggctcgggc aagacgacgg cactgctgcg ctggttgggc gaggcgctgg gggccacgga
86340tgcgagcgtc ctcgtggtct cctgtcggcg cagctttacg cgcacgctgc acgagcggct
86400ccgcgacgcg gggctgccgg ctttcgcgac gtactttgac gcgcggagct acgtgatgac
86460gggcgcggcc taccggcggc tgctggtgca agtggagagc ctgcaccgag tggacgagga
86520gctgctgggc gactacgata tactagtgtt ggacgaagtt atgtccaccc tggcccagtt
86580gtattcgccg acgatggggc gcttgcaccg ggttgacgcg ctgctgcacc ggctgttgcg
86640gcggtgcccg cggattgtgg cgatggacgc gacggtgaac gcgcagctcg tggatttgtt
86700ggcggcgctg cgcggcgcgg gcagcgtgca cgtggtcatc tgcgattatg cgtcggcggg
86760cttctcgcag cggcgctgca ccgtcgcgcg gcggctgggc gcccgcgtgc tggcggcgcg
86820gcttaagggg gacgccgagg acggcgccga agacggcggc gcttcgttct ttacgcggct
86880ccgggcgcgc ctcgaggcgg gccacaacgt ctgcgtcttc tcctcgacgg tgctcttctc
86940ggagctcgcc gcgcgctttt gcctcacctt cacgccctcg gtgctggtgc tcaactccac
87000gcggcccgcg gagggcgatg tgtcgcgctg gcgtgacgtt cgcgtgctca tctacacgac
87060ggtcattacc gtcggcctca gctttgacca cagctacttc cacgcgatgt tcgcctacgt
87120caagcccatg agccacggcc ccgacatggt ctcggtgtac cagtcgctcg ggcgcatccg
87180ctcgctcgtc gacaacgagc tctgcgtgta cttcgacagc agcgccgcgc gccccgagcc
87240cgtgttcacg cccatgctgc taaatcacgt ggtggctgag gacggcggct ggcccgcgac
87300tttctcggag gtcaccaacc tcctctgctg cagcttccgc gcggcgtgcg cccccgcctt
87360tcgcggcgcg cgcggactcg cgctgtttcc gcgcttcaag tacaagcacc tctttgagcg
87420ctgcacgctg gccagcgcga gcgacagcct caacatcctc cacgcgctgc tggagaacaa
87480ccgcgtcggg ttccaactgg aaggctgcgc agcgctcacc gccgcgggat tctgccgctt
87540tctcgcggac gtgcgcgccg acgcggccgc ggccgcggcc gatttgcgcg cattggccgc
87600cggcatcccg tccccggtgt cggccgaggg cctggccgag cacccggccg tggccgcctt
87660cgcggacaag tacttgcgcg cgggcggggc cccgcccgcc gcgctcgaag agctgctgcg
87720cgcgctcaac tgccccgcgg cgcgcgcccg cttcgtaaac ttggccgtgc tcggcggctg
87780cttgcacgtg cccgccgccg ccgaaagcct ggaagtattc gcgggcatct accgccacta
87840cgcctcgggc gaggtgcccg tgctcaccga ggccggcgcc gttgagacgg cggctttggc
87900gcccgggctc gcgctggagg ccaactggcg gctgtttggg ggctgcgccc gcatggcccg
87960ggcgctgggg ctgctgcgcc gccgcggcgg cggcgaagcc gacgacgtcg cagacgccgc
88020ccacggcctc acggagccgg cgatcgtcga gctcgtcggg ccgccggggg ggcacgacta
88080cgcgcagtgc ttactggaaa tcgcccgctg caacatcacg ccggcgggcg tgatggcccg
88140cgggcctgtg gtcgctgtgg ccgcgcggct ttctgggcgg ggctttgcac aggggcgggg
88200cgtggggctg ggcgcggccg cgcacgcggt gagcgtgttc aaagtgatat gggaagaggt
88260gttcggggcc cggctgcaga agagcacgca aaccttcccg ggccacgcgc gcgttaagaa
88320cctgcgcaaa catgaaatcg tcgccctgct ggacttggct ggcatcgacc gcgccggccg
88380cgacacgcac cgcgagttgt atcgcctgct gatgagccac aaggcgcgct tcgcgagccc
88440caagtacagc ctgcgcctcc caaagtgggg ccggctcctt ggcttcgccg cacgcggccc
88500ggagcccggg cccgacgcgc cccccgaagc ctcgctggaa gcggcgctcg cacgcgtccc
88560ggctttgcac tggccttgcg ccgcgggggc ggtcgacttt tgcgcgcttt agccgcgcgg
88620gcctgtgctc gtctgccgta gccctccccc ccccccccct ctttaccgcg ccatgccggt
88680ttcgcacagc aacggctgtg tgtgcggggt ctcgctttat tcggcgtggg ccgcgggccc
88740cgaccgcgcg cgcgtgctgc tcgccctact ctgccgaatg gacgacggcg gctgcgacgc
88800caagttcgcc ctcgtaaacg tgtgtgcgcg tggcgtgacc gcgctcgcgc gcggcgcgag
88860agatgtaacg gccgcgcggc tggaggacct cgcgcgcgcc gccgccgccc cccgagcgct
88920gccgctggca acgctcggcc acgctgcgac gtggaaggcc ctgtacgtaa gtgccctggc
88980ggcgctgcgc gcgcagattg ggccctttcg cttttatcga gagacgcgct ttggagtaga
89040caacgacacc gggttgctgg tgtccgccga ggagcccccc gatgccgccg acgcggcccc
89100gcgggcggcc gtgctgcgct cggcgctacg gctggccgta gaggaagacg cggtgcgcgc
89160ggcggcggcg gcggctcccg ccgggggcgg ctcccttgcg cgcgcgcggc tctgcgccat
89220gcgcgacgga cacgccgacc tctccgcgcc cgggaacgtc gtcgaattcg agctgactac
89280aaagacggcc cgcttctacc gaatctttgc cgacatcgcc cagcccccgc ggaagcgggc
89340cgggcgcctg gcggacgtgt ttgcccaccg ggagtaccgc gtgcgcacag aaggcagcgc
89400cgccccggtg gtcgtgcgcg cgctcgtgcc cgtcaacttt gactgcgtcg tcgccgacgc
89460gcgcgccttt tcgccgatgg ccgccatgct tgtgtttgcg cagtggcacg cggcgctctt
89520taccgacgga ccggcgcagg tcctcggctt tctggggccc cagctgaacc ccggcggcga
89580agagcgcgac tactgcttct tgctggggtt tccgggcgtc ccgctagtag tctcggccgc
89640cgacgccggc gccgtgcgcg atgacttaga cgcgcacgtt ctcacggacg ggctctggcc
89700cgccttcggc gtgcacgtgt accacgcgct cggcccgtgg aactttttgg acggcgccgc
89760cgtcgcaagc ctgaaccgcc gcattgcggc agcgcgcgcc gcgctgccgc cgggcggcag
89820cgacgggtca gattggcccg cgggccgcgt gagcaccatc ttgaacagcc ccgcctgcgt
89880gcgcgggctc tggctggcca agttcgactt ttcggccttt tttcccaccc tgtacgccca
89940tcttgttccc gagaacgcgc gactggcgcg cgctatttgc gcgcgccgcg acgggcgccc
90000tgggctcaag ccttcgctct tgaccttttt tggcgggctg cggcacgtgc acgcgccggc
90060gtacgaggcc gtcatcgcgc tggcgaacgc cgtggcagcc gccgtggagc gcgcggccaa
90120cgcgcgaaac tttgccgtgt gcacgtacgt caaggatggc ttttggggcg ccttcgggga
90180cgcggcgccc gaggttgtgc cgcgcgaggc cgcgctcgcg gcggcgctcg cgctgcgaga
90240cgactgccag cgcgcggcgg aagcggtgct gcgcgccgcg gggctgcacc ccgcagaagg
90300cgccgagctg cacctgcgct tcgagggcct gttcacgcat gccgtttcgt ggtcggccaa
90360caaatactgg ctctgggacg ccaccgcggg gggcgctgag ggtgagctct ttgtgggatt
90420cccctgccgg actgagttcg ggcgcatggc caagcgcagc cttgcggggc tgctgcggcg
90480cgccgtcgcc cagcccgagc gccccagcga cacggtcgcg gccgccgccg cggcctgtga
90540cgcgctcgtt cacgcggcct ttgagcggcg cggcgacgtg cgtttttgga gcgcgaccgc
90600gcccattgcc gactggggcg cggtgccgcg ctcggcgctt tcgggcggcg acctgctgga
90660cgcggaccac ggcccccggc cgtacgtgct tgtggcgggc cacgaggcgg cgcccttccc
90720gctaccctgg gctctctacc gctcccccgt gttgcttccg gacatcgcct gtcgcgctca
90780catggcgcct gtgctgcagg agctggcgcg catgctgaac ggcgccctgg cggccctcgc
90840cgcgcgcgag ggcgacgacg agccgccaat agaagagttc gagtacaacc tggccgattt
90900cgatttttta tttgcctgag gggatggggg ggggaaagga aacatcataa taaaagatgg
90960tagacgatgt ctcagtcgta cgacacaaac atcttgtccg gcgtcagttt gtcggggatg
91020cgcgtccacc aatgatacac cgcgtcgcgg aacgcctgcg cggcgagggg cccgttcagc
91080agccccgggc gcgcgttaat cacgcccggc gggcaccgct ctggcgctgg cccgccgcgc
91140cgcgccgcgc cgccggtgtg gtagatcgcc gtaatcaccg acggggggtt gccggccgct
91200agcagcagcc gggcgacggc gtagtggggc aacaccagct ggctgtcgaa ggggctgtag
91260ccggccatgc acatagccgt atttagcacg cgcatggcgc ccacgtaaag caaccggctc
91320atcttgcgcg caggcggcgg gcgcagacgc cgcagcaggc acgacagctg cacgaacagg
91380gcggccccga cgcgcgcctc gctgcagccc tctaaaaaca tttgcacgac gcagagggca
91440aagtcctccc gcgttttggg gcggcacaag gccagccggt acggcagcac ggcagcgggc
91500acggtagtgg caaagaccgc atcctccatg gcggtgagca cggcgaaggc aaagccccgg
91560aaggccggca tggcttcgca ttcggcacgg tacgcatcgc agtccacttc ttcggcgcgg
91620ccgtcgagcg tcagtagtag cgcgcccgtg ctcggctcta cgcgcaggtg cgtaatggac
91680gatgacgtga acgtcggcgg ccctgctggg atctcgcgga cttcgcagac gaagcgcggg
91740agcgcgttcc acacgaggtc gtcgagcacc tgcggcgggc cacccgagcc ctcgcgcgcg
91800tcctgcagca ggctctccag cgtcgagccc tcaaggggca cgcccagcgt aagtccgtcg
91860tacgcctcgg ccatcctcgc ggcgctcgcg gcggcgcttc tcctcgcggc tgcggctgcg
91920gctgcggctc ttgcttcgcc ctctctcgcg gctgcggctg cggctgcggc tgcggctccc
91980gcttcgctct cgggcaccgc gcgacgcaag gcccagctgc agcgccctgc gcgcgtcggc
92040cgtgaagatc gcagcgagct ccgcgaggta cgtctccagg cgcgtttttt taaacaccgc
92100cccgcatagc tcctcctccg acctgcacgc ctcctggtgc gcgatcagga agccgaagcg
92160ccggacgcgc agcacagaga aaaaatacgg cgccaggatc aaggagatgg agctgttcga
92220gtacacgacc gacacctcct ggccctggtt gttagccgtc cgggcaagct tgaagcagcg
92280gagcagttcc tgctcccaca gccgcgagag ccgctccacg tcatcggcgt acgtggggat
92340gtaccgcgac tgaaagctgt tggcgacgta agagtccggg cccatcagcc cagatatgtc
92400gatgacttcg tgccccaatc cgccgtccgc ggggcccgcc gacagcgacc cgggccggcc
92460ggcggccccg ccccccccgc gcgcggcgtc ggccgcgcgc tgggcggcca gcagcgcgcg
92520ctctcgagcc gcctgcagct cgcgctcgct ggcgcggagc ttgtcggcca ggtcgcggtt
92580ggcgcccttt agcgattcga tggttttgaa gaggttgctg acgtagcctt ccaacatccc
92640gttaatgctg tgcaccacag acgctcggaa ggcgtcctgg atctgctgtc cgcccgcggc
92700cgccgcgcgg cggccgcccg ccgcgccaaa tccgggctgg gaggtgtcca cgtctgagac
92760gtcaaagagc ccggcggccg tgtcgtctag gtacgaacgc acggtctccg agatgtcgcc
92820gatgtgccgc atgcccttca tgttgacgat gagcttgatc aaccgcgccg ccgaggagga
92880cgcggccgcg tcctcgccct caccgagcag cttttccacg gacggcgcgc ccggcgcgct
92940ttcgcccgca gcgccttcgg cgcgccgccc caccagcacc ttcaggggga cggtgttaag
93000cagctggcag agcctcgcgt gctcgcgcag cgcgtggcag gccaggacct cgccgtgcag
93060ccgctgcatg ggcgactcga agagtacgtc gccgccgcgc cacacgggcg cccacagcac
93120gaaacactcg ccctcttcgc cggtgacggc gtcgcgcacg gcaaattgct ttttgcgaaa
93180attgtagaga atctcggtgc ggtcgtagtc gaggaccgtc acggcgccgg cgcatcgcag
93240gaggtccgct gcgaaggcct cgcattccgc cagcacccgc ccggcaacgt ccaggcgccg
93300ggccagctct ccgccaacgg cggaagcggc ccccggcgcc tggacggtgc cggcaccgcg
93360aggccgatgc cgccgcagcg gcaccagccc caggcacacg agccagtcta cgtaccgggc
93420gaagctggcc gggctgccgg cgccccccgc gggaaaggcg gccgcgacgc cccgaacgca
93480ctcaacgagc gacatctgca gcgtgcgcct ccaggtatcg aacacgtgct ccgcgagccg
93540caccacctct gcctcgccgg cggcgccgta tcgcgccgcg atgtcggcgg cgcgcaggcc
93600gcgcgcgcgt gtgtaggcgc gccaatcccg cgccacgtcc tcgtagcgcg cggcgtttag
93660cgttgtgctt aggatggtgg cttgcacttg ccggatcacg gtctccgtgc agcgcacggc
93720gctgtacacg ccctggccct cggtgtagcc cagctccccc agcaggatct ccttgaagag
93780ccgcgtgcgc ggcgtcgggt ggatccgcac ccactcgccc ggcggccccg gagcgcccgg
93840gtcacgtgcc gagccggcca agtttaaggc gcgctcggac acgacgcgct cgcactctgc
93900catcgcccag gtgctccggc cggcgcggcc gcggacgtct gcacgctcgg tcatggagcg
93960cgaggccttt tcagccgagg tcttcctgaa tttcacttcc atgcacgaga tacagccaat
94020cgtcaagcgg atccggcagc tggcggccgc gcggctgccg gcggcggccc ggccgccgct
94080tggctggttc cgcgcggccg cggcggccga gtccccgctg gactttgcgc cgcgcgagct
94140gccttttgcc gcgtacctta tcacggggaa cgcgggctcg ggcaaaagca cctgcatcca
94200aaccctcagc gagacgctcg actgcgtgat cacgggcgcg acgcgcgtcg ccgcgcaaaa
94260cgtctaccta aagctagccg ccgcctacca cagccgtcac atcaacacca tcttccaaga
94320gtttggcttc cgcgccaacc acgtgcaggc gcagctgggc cggcaccagt acgtttgcgc
94380ggccagcccg cccagcatcc aggacgtgca gttccgcgac ctcgtgtact actgggaggt
94440gctgggcgac atctcgcggc ggctgctggg cgcggccgcc tcgcgcgggc agttcgaggc
94500gctgcgcgcg gcggagctcg cggcggggcg cccgcgcggc gccgtggagc ggctcgcgcc
94560ctgcgtccac ggctcacttc cggcgttcgc gcgtagcaac gtgattgtca tcgacgaggc
94620cgggctgctg ggccggcaca tcctcaccgc ggtcgtttac tgctggtggc tcatcaatgc
94680ggcgcacgat tcggcgcagt accgcgacgg ggccatgccc gtcgtggtct gcgtgggttc
94740gcccacgcag accgactctc tcgagtccac cttcgagcac cacaagctaa agtgccgcgt
94800gcgctccagc gagaatgtcc tcacctgcct tatcaccaac cccacgctgc gcgagtacgc
94860cgcgatcccg cacaattgga ccattttcat taacaacaag cgctgccagg agtacgagtt
94920cggcgagctg ctcaaaacac tcgagtacgg cctgcccgtg acggaagagc acctcgcgct
94980cgtggacaag tttgtcgtgc cagacgcctt cattaacaac cccgcgaacc tgcagggctg
95040gacgcggctc tactcttcgc accgcgaggt gagcgcctac atgagccgcc tccacgcgca
95100cctcaaggtc gccgagggcc gcagccgctt tgtggtcttt acgctacccg tgtacacctt
95160tgtcaacatc cgcaccttcg aggactaccg caccgccacg ggccagccgg ggctgggggt
95220ggaaaaatgg ctgcaggcca actcgggccg cattaccaac tactcgcaga gccgcgacca
95280ggacgccagt ccaccgcact gcgaagtgtg ctcggccaag ggactcgtcg tggcgcgctc
95340ggacgtaact tacgtgctca acagccaggt gacggtcacc acgaggctca agaagctggt
95400tttcggattc agcggcacct tcgccgactt tatcgccgtg ctgcgcgacg acgggttcgt
95460cagggcgcag agcgagacct cggtggagta cgcgtatcag tttctggccg cgctgctctt
95520tgggggcatg atcgcctttt acaacttttt gcgcacgccc ggcctggacc cgggccgcgt
95580ggacgaagcc taccggcggc tggcgcgcgc cacgcaggaa gcgctcgggc ccgccgcgga
95640cgacgcggtc gactggcggg ggctggcggc ggaccgcgcc gccggctctg aggccggcgc
95700cggggacaac gacgacgacc tcgtcttcgc ggccctggac gaggggaccc tcgacttgct
95760ctactgcaac tacgagttcc agcgccctac gtccgcccac gaaatctacg cacagtttct
95820gctactgaag aacttgttcg ctgcgcgctt tgacgtctgt cgaaccctgt tcggggcggc
95880cttcgcggac gcgcccttcg aggcttacgt ggacaacctt agcttcaaag gctgcgaggt
95940gttcaccggg agcctgcgcg gcgggctggt ctccatggca ctgcagaccg acacatacac
96000gctgatgggc tacgcccacg cgcccccctc gctgctttcg gaggagcccg gccggcgccg
96060gctccccgac ggcgtcgcgg agctgctgtc gacgctggac gtgcccaaca tcgtggtccg
96120cgaccagcgc ggcttcgtgt ccgtgctgca cacgaacgtc agcgagttcg tggaggcgct
96180ggacgacaag gagctcgaga tggctgtcag cgtcgactac ggcatcagct cgaagctggc
96240catgaccatc gcccgctccc agggcctgag cctcgacaag gtcgccgtat gcttcgcgcg
96300cggaaacctg cggctcaacg ccgtgtacgt agccctgtcg cgcagcgtgt cgtcccgatt
96360tctccgaatg aacctcaacc cgctgcgcga gccccacgag cgggacacga tgatcagcga
96420gcatatatta gccgcactcc gcgacgagaa cgtccacatc gtctactaag ccccgccgcg
96480gccgccgcca tggcgctcgc ggcccccggg cccgggacga cgacgctcat cgcgtactcc
96540ctatacgaaa taaagatggc ccccttgtgg gccttgcccc actgcgagca ggtggtgtgt
96600gagtgcgccg cggggggtcg ctcggtgtcg gtgggcggcg ggctggcgtg cgacgcgctg
96660ccggcaggga cgctcgtgct ccagcacggg cccgccgcca cgctggtcgc agtcgactgc
96720gggtccgaat actgctcgta tgccttcacg cacgccagcg gcgtgcgcaa ctcgctgagc
96780ttgcgcgagg gctccgtgtt cgttgtcccg ttcgacgagt gggcggcaac ggaccgcgcg
96840cgccggctgt gcagccgcgc gcgcggtctg ctggccgtgt gcctgggcgc ccggcgagac
96900atccacgtca ccattacggt gtacggccag agcacagcgc cggcgaccgc gccgcccccc
96960ggcgacgtcc tcgaggctat cctgcaggag tcggagattc gcgactgcga tgcccgcccc
97020tcgggctccc gcccctgcgg cgaagaatga gaccgaggca gttaataaac tcacagttac
97080gctttattgg aatgtgtagt atatggttac gtcttattgg aacgtgcggt aattgggggg
97140gaaagggcgc gtcgggggcg gcggtgggcg gcggtccgcg ctggggaggg accgccgtgc
97200tcgcgcggga ctggcggccg cgtagaggcg cgcggcccgg gcctccgcgg gcggcaggcg
97260ctcttcgttc gcgggtacgg ccgcttccgg tccctcgggg cggcgcgccg cgcgaagact
97320cggtgcccgg cgcacccgcc gggcagcggc gtccgggctg ctttccccga ccgcggcggc
97380cgccgcgcgc agcttagccg cggcggcgcg gttggccgcg agaaactgcg tgtagtccgc
97440caccgtggcc acccgggcct ccccaaagac actgccggcg cgcacgcggg ccatggctac
97500cggtgcggtt gctcgccggg gcgcgagtcg ggaccaagcg tgttgtcgcg gtgtatatac
97560accgggccgg cggcagaaaa ctcgtacacg tacaccggga ccgcggggcg cgtgcctccg
97620tccgaggagc gagtgcagta ctttcgcggt ttccgcgact ggatcaccga gtggagctga
97680tcgcgaacgc gctgcgcatg ggcacgctgg cacagcagga acatctgcag gctcttgttg
97740ctgcgcagcc cgcgcgccgc agcgcgcgcg gcccgcgcgc taagcccgcg ggcttgcgcg
97800ccggaaaaag acgacgtctt tgtgcacgct atggtgtact tggccagcgt gcgcttgagg
97860tccttccgga tcgtgtccgt gagctggcgc cgcccgagct cgtcgataga ggagaccata
97920aacaaggtgt caaaggccac gcagtcgggg tttgggccca gacccgccgc tgccaggccg
97980ggcccggcca acgcaggccc gctgctgcgc tcgccgtcgt cggcgggggc agaagcggaa
98040gcggcggcgg cggcagatac ttgccagccg ccggccgcca gcagagagag gaccggctcg
98100acccgccgca tgaccgcacg ccggcgctgt gctcggcgcg cgcgggctgc gcgcgcctta
98160tacaatgctc cagtcgacgc cgccccggcc gtgctgctcc aggaacgcgt tggcctcggc
98220aaagtgcgtg cagtgaacga agggcgctcg tgacagcggc gaggggtggc tgtacgtcag
98280cacgaggtgc cgcttcccgg ccgccccaaa ggcccgctgg gcgtgcgcgc cccagagcat
98340gaacaccagc gggccgctct ccgcgctcag gcgggccagt accgcgtgca ccagccgccc
98400ccagcccagg ctagagtgcg agcccggcgc cccgctccgc acggtgagcg aggtgttaag
98460cagcagcacg ccgcggcgcg cccagtcctc taggcagccg tgcgacggcc gcggagctcc
98520gggaaagttc ttctgcacgg cagcgtagat gttctggagg ctgggtggga ccggaacgcc
98580gcggttcacg ctaaaagcca agccgtgggc ctgcccgcgg ctgtgatagg ggtcctggcc
98640cagaatgaca accttgatgt cctcgggtgc cgcgtaacgc gtccacgcga agatgtccgc
98700tttcggaggc agcacttgct cgacgcggct ccggcgctcg tattcgcgca gcgcgtgtcg
98760cgtgtagggc atggccagct cgggttccag cacgcgccgc caggcttcgt ggacgccaaa
98820ttcagcggcg aatgcccccc aagtaatggc acgctggtct tctagcgctg ttacgcacgc
98880gggaagtcca ttggggcgcc ggcgcttggg cggcgcggca cccgcaagcg gggacaaaga
98940ctttcggcgc gtttgggccg aagccggggc cgaagccggg gccgaagccg gggccgaagc
99000cggggccgaa gccggggccg aagccggggc cgaagccggg gccggggccg gggccggggc
99060atcgctagcg gtagatgccg tcgccagggc cgcagggacc agtcgtgtgg tatcggggcg
99120gcaggacgca ccctcgcggc ggcggtggca gcggcgcgcg aacttcgtgc ggcaagccga
99180aggcgctatt gaggacttgg atggccaagt ctcgatacac tggagtgtcg gcaagcaccc
99240gccttatatc ttcagcgagc ccacgcgcca cggcgtaggg gttggcccag tacgtctcgc
99300cggtgtcctc gtaccacagc gctgcctcgg gcggcgagca ccgcccgcgg ataaaaatgc
99360ccgccaggcc cggggccgcc tcttcgtgct ggggcctgtc tgcgagcaat aagttgccgc
99420ggcaccgctc agccaagatg gattctgcgc tatccgcgcg ccttgtggcg ccagccggcg
99480ggagccacag cagcgccgcc agcagcgccc aggcgcaagc gcgcgcgacc gccggtgcca
99540tgccgctcgt tgtcgcagcc ggcgcgggag tatatttgcg ccggcccaca tgcgatgtat
99600atatgcacgc ccatcgccgc ccgccggggg ccgaagctaa agggtgggcg gccgggcgga
99660tcttggcccc tgcgacccag cctagcacac actgcgtgtg tgtaggggag aagccgcagg
99720gtacgcggta gccgcatacg ctgcgccagc gtgggagttg cgcagcgcgc cgctcggggc
99780caagatcagc gcgatccgcg gaaattagcc tggagtttgc gccgagcccc gcgccgcgcg
99840ctttcgtttg cgatgtaccg cagccttgcg ccggcgccgc tccaaagcgc gcacgccaag
99900cttggcgcgg ggctgcagtc cggcggaaaa atacaagccc cggcgcgcac gccgagcata
99960acgcgcgccg gaccccaaag gctggctttg cggcgcgcgg cgcgggccgc cgtaaagtca
100020gcgcgatgcg caagccgctg cgcgggtgcg ttggccggcc cggcagtgag ccgccgcggc
100080tttgggcggg gggcagcggc ctgtggtgcg gggtcggagc ggccgggggc cgcttagtgc
100140tttgcgttgc ccgcccccgc ccacgcaccg ttcttatgcc agcgtttgca ccccggcgcg
100200aacgctctac cctcctccct cgaggcaggc gcaacggacc ccgcccagtc catcccactt
100260cgcacaatcg ccaaattttt gtccattagc taaaagtatc tccggccata atcgatgtgt
100320ctgagagggt aataaaacac acccagacgc tcggcactta gctctcgagt gattgcctgg
100380ctgcttgccc cgtttgcgtg gaatgaggcc aaacaagcat ttggcccctg tttgtctaga
100440cggggctttg tgtttttccc acccctgccc ttgcccctgg ccgcctggcc ggccggctaa
100500agtataggcc agaccaaacc ccccgcagca gctctgctcg ctggcgagac cccaaagcgc
100560caattgtggc atatttccgg gtctgaccgc gcctgcactt gcctttggca ttaatatttc
100620agagtttaat attacagaca gacaaaaagc cagataatta caaagtattt gtttttattg
100680attgcgcatg cgcgacctgg gccataaaag ccccgcgcat gcgcgagcag ttactttcgg
100740tttggggatg acagcggcga ctgcggctcg aaagttaagt atgcaggctg ggggtcgcaa
100800atacacggcg gtgcggtgtg gtgggctgcg ggtcgcggag tgggtgggcg gggagccggc
100860cgcggcgatt attgccgcca ggcgctgccg ccgctgcagc ggccgagcag cccggccagg
100920ctcgggccct ggcgaccgcc tggctgcggc gccagggccg cgctgctgcg gcggggggtc
100980cccaggaggc tttctcgcac ccaggcggcc acttccattt cggtgcgccg cctcttctgc
101040gccgagctct cggggccggg gtccaggtcg ccccgcgcca tggcgctcgc tggccttctc
101100tcccggccgg ggttgccatt gcggccgacc tcggcccggg cggctccggc cagggccgga
101160gcgccggccc gccgggggtc ggcggcaggg gcgcggccgg cgggagacgg ggtcggggct
101220cgggtggaaa tagccgcggc ggtgctggta gccgccgcgg taacagcggg gctcggcgcc
101280gagctccgag cgacggaagg tgccgccgcg gcggcagtta ctgccgccgc ggcggcagtt
101340actgccgccg ccgcggccgg ggtcccaatt tgcgcccccg ccgaggccgg ccccggggcc
101400gccgcggggg ccgggtcggc ggggcgggcg ggcgcgttcg ccgtcaggtc tatcactgtg
101460gagatgggcg cgggggctgg ggccggggcc ggggccgggg tcggggcgcg gtctaactct
101520gtccttcttc tccggcgggc ctgcacacgg ggaggcccag cctccccgag cagcctggcc
101580cggcgctccc ctcgtccctc ctcactgccc gccccccagc ccgcggtctc tcccgccgcg
101640actcccaagc ccgctcccct cccctcttct ctgggctcgg ggctgcatgc gcgcgcttgc
101700gccgcggggg ctgcccgcgg cgccgccggc aatcgggggt ctcgtctccc gccgcggctc
101760cgagagctgg ggggcgcgga aactgccgcc gcgcggccgc aagggcggcg cgctagcgac
101820cgaggcgccg gctgcaccgc gggtgtttgt cgacctctag tgctgacata ctgtctttcc
101880gcaggccgcc gagcccgggc cgcgccagac gccccccgcg tgcgcctcga ctcaacctcc
101940gcgtccgtct ccggctccgt ttccgtgtcg tcaatggcgg tcaggtcgga ggtgctgagc
102000cccgacgacg actcttctga ctccgaccaa gagtcgtcct ccgagccctc cgagtccgag
102060tccgaggtgt cgagaaacac caccccacgg ccgccaggag gcgcagactg ctgagggatg
102120aggtgcgagg ggcccaccgt cacgcagcgc gccgccacga acaacaggct gcgcacaaac
102180gcgggggcgt cgtcctcgcc aatcaggggc tccatcgcgt cggccagccc gtcgtcgtcg
102240aagccgcact cggccagcat cgccatcacg tagtccgtca tggccgcgag ctcgcgggcc
102300gtcacggcaa aggtgcccac cagagcgccc tcgacccact ccaccacccg ccgcaggtac
102360ggggcgcccg gcccatgctc cggcgtgttc ggcagcaagg gcaggcgcgg gccgcgcgcg
102420acccggtcaa taaactcctg cgccgcgtcc gcgcctcgcc ccgcgcgccc cccggccg
10247859740DNABovine herpesvirus 1misc_featureUnique Region - Short
5aagcttgctc gcacgcgcgc tcggcgtgag ttcgcaccag catgcagcgg cgcgcgctca
60ctgggcgctc gctccaaacg cagcatccgc gtgtcaatca gctcaaaaca gtcctccgtg
120tagcgctcgc ccgcgacgcg ctcgctgccc agccgaagta catatcgacg atgtggcagg
180ggcgttcttg ccgggccagg gactttcgct ctgagctcgc gctggaaagc gtcggggagc
240cgagtaaagt actggctcat gtttcccacg ggcagggatt gcggatccac gtcggcgttg
300aggtagaagc ggtccgccag cggggcctcg tcctcgtagc actcgtctgg gaagttgtgc
360ggaagcttaa cgaatgttcc gtcgtaaagc tgacgaaaga actgcagcgg tcggcgcggc
420gcgggaacac attcaaagtg aactgcgccc ccagttcggt cgggactcgc gccgggagcg
480ggaactttca ccagcagggg cttggacgag ggcaccaccg gaaaatagtc cggcgggagc
540atagcataca ggccgtcttc ttgctcgtgg cggcacgcct taaagagtcg ccagccacca
600agccccccct cgcatccggg accggtgccg gcggtcgcgg tcgcggtcgc ctctctgctc
660aacggcactg tgctgatcac cacgcggttg ggggtgccct ggcggtacat ggtccctcgg
720cgcggtcaca aagcaaatga ccaaacgccg gcgctgggtg cggcctttaa aggatagcac
780atggcgcgcg cgggggcgag cccctggggc acgggggctc gcgtttggcg gggcggggcg
840ccgccccgcg gtctacgact tcgtagacca gccggaaaag gacaccaccg gccaccagct
900cagggagtgt cggggtatcg tagggcggcc acgggctagc gatggccggg ccgcgccgcg
960ggagccgcca cgccgctccc gcaaacgtac agtccagctg cgcgtaaacc aagcgcgtcg
1020tggcggcaat gtgcgcaaaa ataggcgcgt acaaatcggc ggcgccaaaa acccacatgt
1080ggaagggccg agccctcgcg cggcccgagt tcagcaagtt gtagccgtcg accacgctga
1140cccactccgc cggttggcgg tggcgggcta agccggcgcc cccgggcgcg ggccaagggc
1200gctgtgtcga caaaagccac ccgcgccgct ggcgttgacg ttgacgtcga cgtgcagccc
1260ttcgccgttt ttactagggc gtgatcgaag acaacgaccg tcgtccccag ccggcttgcc
1320gtcagcgccc ggctctgctc ggcaaggaaa cgccacaccc gcgcgggcac gtctgggctt
1380gcccctggaa gggcgccgcg cctatccgca cacgtgacta tagtcaccat ggcgaccgcc
1440acggcaacgc ttaagtacgg gccgcggcga tcgcgggcgt cgatcgcgtg cggcttggag
1500tccggctgcc gtttctgccg caagcgcgat cccgcgacac gacccgacgt tcttgggcac
1560ccatggagcg cgcggcggag cggctggccc ggcagcgggc gcgcggcctt tggcgctccc
1620gctttgcctg ctgcgtcgcc gcggagccga gcggggagcc ggctcggcca gagcgttcgc
1680ggagccgctg cggctccgcg cgctgcgctg cggcgggctc tgcggattta tacttggccg
1740tcaacaacga gggaccggag gtcgcgccgc cggccagaac cggtccgccg gacgcggacg
1800ggatcgaagg gggggctgcc gtcgggaacg agcagggagg ggtcgccgct ggaaacgaga
1860gaagagctgc catcggggac gaaaaaaaaa gcgcctccgg gggcgagaat gagagcgaaa
1920gcgagagcga aagcgagagc gaaagcggga gcgaaagcgg ggccgacgac ggcgactggg
1980acgacgatga cgacgccggg cctgccggcg gggtcacgcg cgaagaggcc gagggcgccg
2040cccgtgcgct aaactttcgc attatccggc ggttgacccc cggctcggag ggacgcgtgt
2100ttgaggcaac ggggcctgct cccgcgcagg agcacgtggt gctcaagatc ggggcctcgg
2160cctctacgct ggccgaggct atgctactgc gaaccttgga ccacgccaac gtggtcaagc
2220tgaaggccgt gctcttccac ggggagctgg tgtgcgtggt gctggcgcgc taccgcgagg
2280acctgcacac gcacctctgg agaatcaacc gcccgctggc gctccccgcg gcgctggcgg
2340tgacgcgggc cgtgctgcgg ggcctcgcgt acctgcactc ccgccggatc gctcaccggg
2400acgtcaaaac ggaaaacgtc ttcctcaacg gcccaggcga cgtgtgcctg ggcgactttg
2460gcgcggcaca cgggccggtc accgagcccc gctactacgg cctggccggc accctggaga
2520cgaactcgcc agagctgctg gcgcgcgcgc gctacgactg ccgcacggac gtgtggagcg
2580cgggcgtcgt cgcgtacgag atgctggcat acccgcgcgc gctgttcgac agccccgcgg
2640gcccgcaggg cgaggacgcc gaggcatcgg gcccgccgac gatcttgggc gaccgcgact
2700gcgcccggca gctgctccgc gtgattcgcc ggctggccgt gcacgccgaa gagtttccac
2760ccagccccac tgaccggctg acccgcaact tcaagcgcca cgcgagcacg cgccgagagc
2820cgcacagccc gtaccgctgc ctggcggtgc tccggctgcc ctgcgacgcc gaccgcctcc
2880tacaccagat gctgaccttt gactttcgcg cgcgccccac cgccgcggag ctgctggagc
2940accccgtctt cggtgcggcc tcggggtagc cccgggggtt tcccgcaaaa ctgaggcata
3000taaggcgcgg gcaccggcaa gtttggcatc cacacttcgc gctgtggaca cgagagcgaa
3060cgcgagcgaa cgcgagcgca agcgcgagca cacgactgcg atcatgcctg ccgcccggac
3120cggcaccttg gccgccgtcg ccctaatcct gctctgcggg gccgccgttt tggggcgccc
3180cgcgcccgac gacctctgtt tcgccgacgt gcgccgcact ggcatggcgc cctcccgccc
3240gctggggccc gtcctgaacc tagcggcctc ggatttgacc tcgcgggttt cggtgcgcgc
3300ggtggacgct tcgcgcggct gcgccctggc cctcttggac atggcggaga cggtggtgcc
3360cggcggaccg cgagccgccg acgtcgtcga cgtcggctgg gcttaccaag acggggactg
3420catggtgcct ctggcatatc gccagtactt taactgcacg gggggcgcgc tgcccggcca
3480aaacgtctgc gccgggctct ctgagacccg catccgcggt ggctttggaa cctccgacta
3540cgcgctctac gggacgtcgc tagtactgcg ccccggcctg tacgaccgcg ggacctacat
3600ctacttcctt ggatacggcc cagacgacat ctacgtgggc agcgtcacgc tcatggtggg
3660cgccgacatc cacaaatacc cctgcgggct ggaccgaggg ctcggtgtgg ccctgcacca
3720caagagcgga ccggcccgac ctctgacaga ggacgacgcc accggcgact gggcctgcgg
3780ctgcttcccc gcccttgttg aggttgacgc ggtgtggggc aacgtaagcg ccgcagagct
3840gggcctggcc gacccgatcg actacgccga cgaagggggt gaggtcgaag tgctcgagga
3900cgaagccggg agcgccagcg gaaacctgcc gcaggacgac cccgaccccg acctcgcaga
3960ttgccggacc gtcgggctct ttagcgaaag cgacatgttc cggaccgcca gcgggcccga
4020atcgctgctg atcggcgccg ttgccaagga cgtcctgacg gtgcccctca atctgccgcc
4080cggccgctct tacgaggccc tgcgaaacgc atcgctggag tgcaactccc gcccgcgcga
4140gaccggcgac gcagcggtgg tggtgatgtc tctccaggag cccgctcgcc tcgagcgccg
4200ccccgatgcc cgcgccaccg atccggagtt tgggctcttt ggcctgcccg atgaccccgc
4260cgtgcggcgc ggcattctca tcggcctcgc gatcgctctg ctggtgctgc tgttttcgct
4320ggtgatcgtg ctcgtctgcg cctgccggct cgcccgcgca gccaaggctg cgcgacgcgc
4380ccgcgccgcc acgttcgcca agagcaaccc cgcgtacgag ccgatgctca gcgtctgatc
4440gccggcaccc cacgccgccc cgaccccgct gtcccgcgtt tacaataaac agttattctt
4500accaacgttg gtgcgcctgt cgcgtgtcta ttgcgagtta aaccgagtgc cccacccagg
4560cagggcgggg gttgggccgg gccgcagccc cggctgggta tatatccccg acgggcgact
4620agagatacac tcgccccgcg cggctgctgc gagcgggcga acatgcaagg gccgacattg
4680gccgtgctgg gcgcgctgct cgccgttgcg gtgagcttgc ctacacccgc gccgcgggtg
4740acggtatacg tcgacccgcc ggcgtacccg atgccgcgat acaactacac tgaacgctgg
4800cacactaccg ggcccatacc gtcgcccttc gcagacggcc gcgagcagcc cgtcgaggtg
4860cgctacgcga cgagcgcggc ggcgtgcgac atgctggcgc tgatcgcaga cccgcaggtg
4920gggcgcacgc tgtgggaagc ggtacgccgg cacgcgcgcg cgtacaacgc cacggtcata
4980tggtacaaga tcgagagcgg gtgcgcccgg ccgctgtact acatggagta caccgagtgc
5040gagcccagga agcactttgg gtactgccgc taccgcacac ccccgttttg ggacagcttc
5100ctggcgggct tcgcctaccc cacggacgac gagctgggac tgattatggc ggcgcccgcg
5160cggctcgtcg agggccagta ccgacgcgcg ctgtacatcg acggcacggt cgcctataca
5220gatttcatgg tttcgctgcc ggccggggac tgctggttct cgaaactcgg cgcggctcgc
5280gggtacacct ttggcgcgtg cttcccggcc cgggattacg agcaaaagaa ggttctgcgc
5340ctgacgtatc tcacgcagta ctacccgcag gaggcacaca aggccatagt cgactactgg
5400ttcatgcgcc acgggggcgt cgttccgccg tattttgagg agtcgaaggg ctacgagccg
5460ccgcctgccg ccgatggggg ttcccccgcg ccacccggcg acgacgaggc ccgcgaggat
5520gaaggggaga ccgaggacgg ggcagccggg cgggagggca acggcggccc cccaggaccc
5580gaaggcgacg gcgagagtca gacccccgaa gccaacggag gcgccgaggg cgagccgaaa
5640cccggcccca gccccgacgc cgaccgcccc gaaggctggc cgagcctcga agccatcacg
5700cacccccccg ctacgcccgc ggcccccgac gccgtgccgg tcagcgtcgg gatcggcatt
5760gcggctgcgg cgatcgcgtg cgtggccgcc gccgccgccg gcgcgtactt cgtctatacg
5820cgccggcgcg gtgcgggtcc gctgcccaga aagccaaaaa agctgccggc ctttggcaac
5880gtcaactaca gcgcgctgcc cgggtgagcg gcctaggccc tcccccgacc gccccctttg
5940ctcctagccc cggctcctgc cgagccgcgc ggggcgggag ataaagcgcc cgcgcgtcgg
6000cgactcaagc cattgccgcg accttgtcct ccggcgcgct cgcgatgcgg tgcctgttgc
6060tctggatggt ggtgctggcc gcgcgagcgg cgcccgctcg cagccttgtg tatcgcggcg
6120aggcagtcgg cctgcgcgcg gacggccccg tagcgttcgc tgtccacccg accgacgcaa
6180cgctcgcgct gcggggccgg ctgattttcc tggaacacca gctcccggcc gggcggcgct
6240acaacgggac cgtcgagctg ctgcgctacc acgccgcggg cgactgcttc gttatgctgc
6300agacgaccgc gttcgcctcc tgcccgcgcg tcgcgaacga cgcctttcgc tcctgcctgc
6360acgccgacac gcgccccgct cgcagcgagc ggcgcgcgag cgccgcggtc gaaaaccacg
6420tgctcttctc catcgcccat ccgcgcccaa tagactcagg gctctacttt ctgcgcgtcg
6480gcatctacgg cggcaccgcg ggcagcgagc gccgccgaga cgtctttccc ttggccgcgt
6540ttgtacacag cttcggtgag cccggagacc cagaggccgc ggccgcgcac cccggcgccg
6600tcgaggcagt cgcgacccgc tgcgagcggg gcctcgacgc cagctcggcg agcctctacg
6660accgcgcgct ggcggcgttc cccgcaggcg ccgccaccac gcccggcccc accgcgagca
6720gcgggagcgg ggccgcgacg ccggagaggg tcgacgagac gacggaagtc aaggccgcga
6780cgagagcggg ctcggcgttt gccctcacca cgcccccggc cggcctgacc gccagccccg
6840ccgccagccc ctcccgtgcc tttagcgcgg ccgccccggc cgccgctgcg cagccggccg
6900gagacacgcc cgctcgcttc cggcgccaac tggcgtcgat cctagtgcct ctgtgcgtgc
6960tggtgctgct gctgcttgcg ctctgcgccg cgacggtaaa ctgcgcgctg cgccgccgcc
7020tgctgccgtg ctctcggcgc gtttacaagc cgcggacgtg cgcgacatgc gggagcggca
7080cttgcgcggg gcggcccccc tgccgcggcg cggcaccgag cgccccagcc accgtcgtgg
7140cactgggctc ccggccaaag gcgccccccc tcgccaccat cagcgaagaa taaacgccgc
7200gcgcggcaaa cgatctcgct cgcgtgtgtc ttggtttctg cgcggcgggc ggggtgggga
7260gcgggcaagg cggaggaaga ccgggggcag gagctgcgtg gagggcggag ccgttgagcg
7320gcccgaccgc cgccgggttg ttaaatgggt ctcgcgcggc tcgtggttcc acaccgcgcc
7380ggagaaccag cgcgagcttc gctgcgtgtg tcccgcgagc tgcgttccgg ggaacggcgc
7440acgcgagagg gttcgaaaag ggcatttggc aatgcaaccc accgcgccgc cccggcggcg
7500gttgctgccg ctgctgctgc cgcagttatt gcttttcggg ctgatggccg aggccaagcc
7560cgcgaccgaa accccgggct cggcttcggt cgacacggtc ttcacggcgc gcgctggcgc
7620gcccgtcttt ctcccagggc ccgcggcgcg cccggacgtg cgcgccgttc gcggctggag
7680cgtcctcgcg ggcgcctgct cgccgcccgt gccggagccc gtctgcctcg acgaccgcga
7740gtgcttcacc gacgtggccc tggacgcggc ctgcctgcga accgcccgcg tggccccgct
7800ggccatcgcg gagctcgccg agcggcccga ctcaacgggc gacaaagagt ttgttctcgc
7860cgacccgcac gtctcggcgc agctgggtcg caacgcgacc ggggtgctga tcgcggccgc
7920agccgaggag gacggcggcg tgtacttcct gtacgaccgg ctcatcggcg acgccggcga
7980cgaggagacg cagttggcgc tgacgctgca ggtcgcgacg gccggcgcgc agggcgccgc
8040gcgggacgag gagagggaac cagcgaccgg gcccaccccc ggcccgccgc cccaccgcac
8100gacgacacgc gcgcccccgc ggcggcacgg cgcgcgcttc cgcgtgctgc cgtaccactc
8160ccacgtatac accccgggcg attcctttct gctatcggtg cgtctgcagt ctgagttttt
8220cgacgaggct cccttctcgg ccagcatcga ctggtacttc ctgcggacgg ccggcgactg
8280cgcgctcatc cgcatatacg agacgtgcat cttccacccc gaggcaccgg cctgcctgca
8340ccccgccgac gcgcagtgca gcttcgcgtc gccgtaccgc tccgagaccg tgtacagccg
8400gctgtacgag cagtgccgcc cggaccctgc cggtcgctgg ccgcacgagt gcgagggcgc
8460cgcgtacgcg gcgcccgttg cgcacctgcg tcccgccaat aacagcgtag acctggtctt
8520tgacgacgcg ccggctgcgg cctccgggct ttacgtcttt gtgctgcagt acaacggcca
8580cgtggaagct tgggactaca gcctagtcgt tacttcggac cgtttggtgc gcgcggtcac
8640cgaccacacg cgccccgagg ccgcagccgc cgacgctccc gagccaggcc caccgctcac
8700cagcgagccg gcgggcgcgc ccaccgggcc cgcgccctgg cttgtggtgc tggtgggcgc
8760gcttggactc gcgggactgg tgggcatcgc agccctcgcc gttcgggtgt gcgcgcgccg
8820cgcaagccag aagcgcacct acgacatcct caaccccttc gggcccgtat acaccagctt
8880gccgaccaac gagccgctcg acgtggtggt gccagttagc gacgacgaat tttccctcga
8940cgaagactct tttgcggatg acgacagcga cgatgacggg cccgctagca acccccctgc
9000ggatgcctac gacctcgccg gcgccccaga gccaactagc gggtttgcgc gagcccccgc
9060caacggcacg cgctcgagtc gctctgggtt caaagtttgg tttagggacc cgcttgaaga
9120cgatgccgcg ccagcgcgga ccccggccgc accagattac accgtggtag cagcgcgact
9180caagtccatc ctccgctagg cgcccccccc ccgcgcgctg tgccgtctga cggaaagcac
9240ccgcgtgtag ggctgcatat aaatggagcg ctcacacaaa gcctcgtgcg gctgcttcga
9300aggcatggag agtccacgca gcgtcgtcaa cgaaaactat cgaggcgctg atgaggccga
9360tgcagcgccc ccttcaccgc cgccggaagg ctccatcgtg tccatcccca tcctcgagct
9420caccatcgag gacgcgccgg ccagcgcaga agcaaccggc accgcggcag ccgcacccgc
9480tgggcgcact ccagacgcga acgcagcacc cggcggctac gtgccagttc ccgcggcgga
9540tgtggactgc tattatagcg aaagcgacag cgagacggca ggcgagtttt tgatacgcat
9600ggggcggcag cagcggcggc ggcatcggcg gcggcgctgc atgatagcag cggccctgac
9660ttgcattggc ctcggggcct gcgcggcggc ggcagcggca ggcgccgtcc tggcgttgga
9720ggtagtgccc cggccctgag
9740
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