KR20190074702A - Novel shiga toxin producing Escherichia coli specific bacteriophage ECOH1 and antibacterial composition comprising the same - Google Patents

Novel shiga toxin producing Escherichia coli specific bacteriophage ECOH1 and antibacterial composition comprising the same Download PDF

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KR20190074702A
KR20190074702A KR1020170176257A KR20170176257A KR20190074702A KR 20190074702 A KR20190074702 A KR 20190074702A KR 1020170176257 A KR1020170176257 A KR 1020170176257A KR 20170176257 A KR20170176257 A KR 20170176257A KR 20190074702 A KR20190074702 A KR 20190074702A
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김영주
장봉근
한범구
김현일
박철세
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Abstract

The present invention relates to a novel bacteriophage ECOH1 specific to Shiga toxin-producing Escherichia coli and, more specifically, to an antibacterial composition comprising the bacteriophage ECOH1 specific to Shiga toxin-producing Escherichia coli. According to the present invention, the bacteriophage ECOH1 shows extremely high specificity to Shiga toxin-producing Escherichia coli; may be transfected into Shiga toxin-producing Escherichia coli to propagate inside the Shiga toxin-producing Escherichia coli, thereby showing excellent bacteriolytic activities; and is highly resistant to physicochemical stimuli. In addition, the bacteriophage ECOH1 of the present invention does not transfect hosts other than bacteria, such as humans, animals, and plants, and thus serves to solve the problems associated with antibiotic-resistant bacteria due to overuse and misuse of antibiotics, the problems associated with antibiotics remaining in food, and the problems associated with a broad range of hosts. Thus, the bacteriophage ECOH1 may be widely used in the fields relating to antibiotic compositions, feed additive compositions, feed, disinfectants, or detergents.

Description

신규한 시가톡신 생성 대장균 특이 박테리오파지 ECOH1 및 이를 포함하는 항균 조성물{Novel shiga toxin producing Escherichia coli specific bacteriophage ECOH1 and antibacterial composition comprising the same}A novel cytotoxin-producing E. coli -specific bacteriophage ECOH1 and an antimicrobial composition comprising the same, wherein the microorganism comprises Escherichia coli specific bacteriophage ECOH1 and antibacterial composition,

본 발명은 신규한 시가톡신 생성 대장균 특이 박테리오파지 ECOH1에 관한 것으로서, 더욱 상세하게는 상기 시가톡신 생성 대장균 특이 박테리오파지 ECOH1을 포함하는 항균 조성물에 관한 것이다.The present invention relates to a novel cytotoxin-producing E. coli-specific bacteriophage ECOH1, and more particularly to an antimicrobial composition comprising the above-mentioned cytotoxin-producing E. coli-specific bacteriophage ECOH1.

시가톡신 생성 대장균(Shiga Toxin-producing E. coli, STEC)은 단백질 독소인 시가톡신(Shiga toxin)이라는 독소를 만들어내 질병을 유발한다. 상기 시가톡신 생성 대장균에는 시가 유사독소(Shiga-like toxin, SLT)인 베로독소(Verotoxin)을 생산하는 베로독소 생성 대장균(Verocytotoxic E. coli, VTEC) 및 장관출혈성 대장균(Enterohemorrhagic E. coli, EHEC)이 속한다.Shiga Toxin-producing E. coli (STEC) produces toxins called Shiga toxins, a protein toxin, that cause diseases. The cigar toxins produced E. coli is similar to Shiga toxin (Shiga-like toxin, SLT) of Vero Vero toxin producing E. coli produce toxins (Verotoxin) (Verocytotoxic E. coli, VTEC) and secretary hemorrhagic Escherichia coli (Enterohemorrhagic E. coli, EHEC) .

시가톡신 생성 대장균 중 장관출혈성 대장균은 베로독소(Verotoxin)를 생성하여 대장점막에 궤양을 유발하여 조직을 짓무르게 하고 출혈을 유발한다. 상기 장관출혈성 대장균은 혈청형에 따라 O26, O103, O104, O146 및 O157 등이 있으며, 대표적인 장관출혈성 대장균은 O157:H7이 있다. 장관출혈성 대장균 O157:H7에 감염된 개체의 치사율은 1,000명 당 6 내지 7명 정도로 낮은 편이나, 전염성이 강해 짧은 시간에 퍼지며, 소량의 균이 감염이 되더라도 병원성을 나타낼 수 있어 위해성이 높다고 할 수 있다. 장관출혈성 대장균 O157:H7 감염을 유발하는 원인식품의 경우 광범위하게 분포하기 때문에 환자와 보균자의 분변으로부터 직·간접으로 오염되는 식품이면 모두 원인식품이 될 수 있으며, 축산물, 육류 가공품, 햄, 치즈, 소시지, 채소샐러드, 분유, 두부, 음료수, 어패류, 도시락, 급식 등이 주요 원인식품이다.Shiga toxin-producing Escherichia coli produces verotoxin, which causes ulceration in the large intestine mucosa, causing irritation and bleeding. The intestinal hemorrhagic Escherichia coli has O26, O103, O104, O146, and O157 according to the serotype, and representative intestinal hemorrhagic Escherichia coli is O157: H7. The mortality rate of individuals infected with intestinal hemorrhagic Escherichia coli O157: H7 is as low as 6 to 7 per 1,000, but it is highly infectious and spreads in a short time, . Foods that cause intestinal hemorrhagic Escherichia coli O157: H7 infection are widely distributed, so any food contaminated directly or indirectly from the feces of patients and carriers may be the causative food and may be caused by livestock products, meat products, ham, cheese, Sausage, vegetable salad, powdered milk, tofu, beverage, seafood, lunch, lunch, etc. are the main causes of food.

상기 장관출혈성 대장균 O157:H7에 감염된 경우 주요 증상으로는 혈변, 발열, 구토, 설사와 복통이 가장 흔한 증상이며, 심각하게는 적혈구와 신장에 손상을 일으킬 수 있다. 대부분의 장관출혈성 대장균 O157:H7 감염은 7 내지 10일 정도면 회복되지만, 감염자 중 약 15%는 용혈성요독증후군(Hemolytic Uremic Syndrome, HUS)으로 발전하기도 하며, 대장균 감염에 민감한 사람들 즉, 임산부, 면역취약자, 영유아, 노인 등은 심각한 합병증에 걸릴 위험성이 높다.The major symptom of infection with the intestinal hemorrhagic Escherichia coli O157: H7 is the most common symptoms of stool, fever, vomiting, diarrhea and abdominal pain, and can seriously damage red blood cells and kidneys. Most intestinal hemorrhagic Escherichia coli O157: H7 infections are recovered by about 7 to 10 days, but about 15% of infections develop into Hemolytic Uremic Syndrome (HUS), and people who are susceptible to E. coli infection, such as pregnant women, Vulnerable children, infants, and elderly people are at high risk for serious complications.

한편, 박테리오파지(bacteriophage)는 특정 세균을 감염시켜 감염된 세균의 성장을 억제하고 저해하는 세균 특이적 바이러스를 의미한다. 박테리오파지는 박테리아에 감염(infection)한 후 박테리아 세포 내부에서 증식을 하고, 증식 후 자손 박테리오파지들이 박테리아 밖으로 나올 때 숙주인 박테리아의 세포벽을 파괴하는 방식으로 박테리아를 사멸시키는 능력을 갖고 있다. 박테리오파지의 박테리아 감염 방식은 매우 특이성이 높아서 특정 박테리아에 감염할 수 있는 박테리오파지의 종류는 일부로 한정된다. 즉, 특정 박테리오파지는 특정 범주의 박테리아에만 감염할 수 있고 이로 인하여 특정 박테리오파지는 특정 박테리아만을 사멸시키며 다른 박테리아에는 영향을 주지 않는다. 따라서 최근 세균성 질환의 대처 방안으로 박테리오파지의 활용이 크게 주목을 받고 있으며, 자연 친화적 방식의 선호로 인하여 박테리오파지에 대한 관심은 어느 때보다 높다고 할 수 있다. 기존 항생제의 대체 물질로의 개발 가능성이 부각되면서 다시 박테리오파지가 항-박테리아제로 주목을 받고 있다. 이러한 박테리오파지가 여러 세균성 질병을 대상으로 활발히 연구되고 있으며, 박테리오파지를 이용한 대장균 O157:H7의 제어는 안전한 식품에 의한 질병의 위험을 감소할 수 있는 방안이 될 수 있을 것으로 판단된다.On the other hand, bacteriophage refers to a bacterium-specific virus that infects a specific bacterium to inhibit and inhibit the growth of the infected bacterium. Bacteriophages have the ability to kill bacteria by infecting bacteria, multiplying inside bacterial cells, and destroying the cell walls of the host bacteria when the progeny bacteriophages come out of the bacteria after proliferation. The bacteriophage infection method of bacteriophage is highly specific, so the type of bacteriophage that can infect a specific bacterium is limited to some. That is, certain bacteriophages can infect only a specific category of bacteria, which causes certain bacteriophages to kill only certain bacteria and not other bacteria. Recently, the use of bacteriophage has attracted much attention as a countermeasure against bacterial diseases, and interest in bacteriophage is higher than ever due to preference of nature friendly method. Bacteriophage is attracting attention as an anti-bacterial agent again with the possibility of development as a substitute for existing antibiotics. These bacteriophages are actively studied for various bacterial diseases, and control of E. coli O157: H7 using bacteriophage may be a way to reduce the risk of disease caused by safe foods.

이에 본 발명자들은 박테리오파지를 기존 항생제의 대체 물질로 활용하기 위하여, 하수로부터 시가톡신 생성 대장균 특이 박테리오파지를 분리하였고, 분리된 박테리오파지의 형태적 및 유전학적 특성 분석을 통해 시가톡신 생성 대장균을 선택적으로 사멸시킬 수 있음을 확인함으로써 본 발명을 완성하게 되었다.Therefore, in order to utilize bacteriophage as a substitute for existing antibiotics, the present inventors have isolated a specific bacteriophage of ciguatoxin-producing E. coli from sewage and selectively analyzed the morphological and genetic characteristics of the isolated bacteriophage to kill the cytotoxin-producing E. coli The present invention has been completed.

따라서 본 발명의 목적은, 시가톡신 생성 대장균에 특이적인 사멸능을 갖고, 서열번호 1로 표시되는 염기서열로 이루어진 박테리오파지 ECOH1을 제공하는 것이다.Therefore, an object of the present invention is to provide a bacteriophage ECOH1 having the nucleotide sequence shown in SEQ ID NO: 1, which has a killing activity specific to the cytotoxin-producing E. coli.

본 발명의 다른 목적은 상기 박테리오파지 ECOH1을 포함하는 항생용 조성물을 제공하는 것이다.Another object of the present invention is to provide an antibiotic composition comprising the bacteriophage ECOH1.

본 발명의 또 다른 목적은 상기 박테리오파지 ECOH1를 포함하는 사료 첨가제를 제공하는 것이다.Yet another object of the present invention is to provide a feed additive comprising the bacteriophage ECOH1.

본 발명의 또 다른 목적은 상기 박테리오파지 ECOH1를 포함하는 소독제를 제공하는 것이다.Yet another object of the present invention is to provide a disinfectant comprising the bacteriophage ECOH1.

본 발명의 또 다른 목적은 상기 박테리오파지 ECOH1를 포함하는 세척제를 제공하는 것이다.Yet another object of the present invention is to provide a detergent comprising said bacteriophage ECOH1.

본 발명의 또 다른 목적은 상기 박테리오파지 ECOH1를 개체에 투여하는 단계를 포함하는 시가톡신 생성 대장균에 의한 감염성 질병의 예방 또는 치료 방법을 제공하는 것이다.It is still another object of the present invention to provide a method for preventing or treating an infectious disease caused by a cytotoxin-producing E. coli comprising the step of administering the bacteriophage ECOH1 to an individual.

상기 목적을 달성하기 위하여, 본 발명은 시가톡신 생성 대장균에 특이적인 사멸능을 갖고, 서열번호 1로 표시되는 염기서열로 이루어진 박테리오파지 ECOH1을 제공한다.In order to accomplish the above object, the present invention provides bacteriophage ECOH1 having the nucleotide sequence shown in SEQ ID NO: 1 and having a killing activity specific to the cytotoxin-producing E. coli.

또한 본 발명은 상기 박테리오파지 ECOH1을 포함하는 항생용 조성물을 제공한다.The present invention also provides an antibiotic composition comprising the bacteriophage ECOH1.

또한 본 발명은 상기 박테리오파지 ECOH1를 포함하는 사료 첨가제를 제공한다.The present invention also provides a feed additive comprising the bacteriophage ECOH1.

또한 본 발명은 상기 박테리오파지 ECOH1를 포함하는 소독제를 제공한다.The present invention also provides a disinfectant comprising the bacteriophage ECOH1.

또한 본 발명은 상기 박테리오파지 ECOH1를 포함하는 세척제를 제공한다.The present invention also provides a detergent comprising the bacteriophage ECOH1.

또한 본 발명은 상기 박테리오파지 ECOH1를 개체에 투여하는 단계를 포함하는 시가톡신 생성 대장균에 의한 감염성 질병의 예방 또는 치료 방법을 제공한다.The present invention also provides a method for preventing or treating an infectious disease caused by a cytotoxin-producing E. coli comprising the step of administering the bacteriophage ECOH1 to an individual.

본 발명에 따른 박테리오파지 ECOH1은 시가톡신 생성 대장균에 대한 특이성이 매우 높고, 시가톡신 생성 대장균에 감염하여 시가톡신 생성 대장균 내에서 증식함으로써 용균 활성이 우수하며, 물리화학적 자극에 강하다는 장점을 가지고 있다. 또한 본 발명의 박테리오파지 ECOH1은 사람, 동물, 식물 등 세균 외의 다른 숙주에는 감염되지 않으므로, 항생제의 오남용으로 인한 항생제 내성균의 문제점, 식품 내의 항생제 잔류 문제, 광범위한 숙주범위의 문제점을 해결할 수 있는바, 항생용 조성물, 사료 첨가용 조성물, 사료, 소독제 또는 세척제 분야에서 다양하게 활용될 수 있다.The bacteriophage ECOH1 according to the present invention has a very high specificity to the cytotoxin-producing E. coli, and has an advantage of being excellent in lytic activity and strong against physicochemical stimulation because it infects the E. coli producing cigatotoxin and proliferating in the cigatotoxin-producing E. coli. Further, since the bacteriophage ECOH1 of the present invention is not infected with any host other than bacteria such as human, animal, and plant, problems of antibiotic resistant bacteria caused by misuse of antibiotics, antibiotic residues in foods, and problems in a wide host range can be solved, A composition for feed addition, a feed, a disinfectant or a detergent.

도 1은 본 발명에 따른 박테리오파지 ECOH1의 시가톡신 생성 대장균 O157:H7에 대한 용균반 형성 활성을 확인한 결과를 나타낸 도이다.
도 2는 본 발명에 따른 박테리오파지 ECOH1의 전체 유전자를 분석한 결과를 나타낸 도이다.
도 3은 전자 현미경을 통해 본 발명에 따른 박테리오파지 ECOH1의 형태학적 특성을 확인한 결과를 나타낸 도이다.
도 4는 SDS-PAGE를 통해 본 발명에 따른 박테리오파지 ECOH1의 단백질 패턴을 확인한 결과를 나타낸 도이다.
도 5는 본 발명에 따른 박테리오파지 ECOH1의 pH 안정성을 확인한 결과를 나타낸 도이다.
도 6은 본 발명에 따른 박테리오파지 ECOH1의 열 안정성을 확인한 결과를 나타낸 도이다.
Brief Description of the Drawings Fig. 1 is a graph showing the results of confirming the solubilization activity of bacteriophage ECOH1 according to the present invention on the cytotoxin-producing E. coli O157: H7.
FIG. 2 is a graph showing the results of analysis of whole genes of bacteriophage ECOH1 according to the present invention. FIG.
FIG. 3 is a graph showing the morphological characteristics of the bacteriophage ECOH1 according to the present invention through an electron microscope.
FIG. 4 is a diagram showing the result of confirming the protein pattern of the bacteriophage ECOH1 according to the present invention through SDS-PAGE. FIG.
FIG. 5 is a graph showing the pH stability of the bacteriophage ECOH1 according to the present invention. FIG.
6 is a graph showing the result of checking the thermal stability of the bacteriophage ECOH1 according to the present invention.

이하, 본 발명을 상세히 설명한다.Hereinafter, the present invention will be described in detail.

본 발명은 시가톡신 생성 대장균(Shiga Toxin-producing Escherichia coli, STEC)에 특이적인 사멸능을 갖는, 서열번호 1로 표시되는 염기서열로 이루어진 박테리오파지 ECOH1을 제공한다.The present invention relates to a method for producing Shiga toxin-producing Escherichia Bacteriophage ECOH1 comprising the nucleotide sequence shown in SEQ ID NO: 1, which has a killing activity specific to E. coli , STEC.

본 발명에서, 용어 “시가톡신 생성 대장균(Shiga Toxin-producing Escherichia coli, STEC)”은 시가톡신(Shiga toxin)을 생성하거나, 시가 유사 독소(Shiga-like toxin, SLT)인 베로독소(Verotoxin)를 생성하는 대장균을 의미한다.In the present invention, the term " Shiga Toxin-producing Escherichia coli , STEC) "refers to Escherichia coli that produces Shiga toxin or produces Verotoxin, a Shiga-like toxin (SLT).

본 발명의 시가톡신 생성 대장균은 장관출혈성 대장균(Enterohaemorrhagic E. coli, EHEC), 장병원성 대장균(Enteropathogenic E. coli, EPEC) 및 베로독소 생성 대장균(Verocytotoxic E. coli, VTEC)으로 구성된 군으로부터 선택된 1종 이상일 수 있으며, 바람직하게는 장관출혈성 대장균 O157:H7일 수 있다.The cytotoxin-producing Escherichia coli of the present invention can be used for enterohaemorrhagic E. coli , EHEC), Enteropathogenic E. coli (EPEC), and Verocytotoxic E. coli (VTEC), and preferably can be at least one selected from the group consisting of intestinal hemorrhagic Escherichia coli O157: H7 .

본 발명에서, 용어 박테리오파지(bacteriophage)는 특정 세균에 감염하여 당해 세균의 성장을 억제하고 저해하는 세균 특이적 바이러스로, 단일 혹은 이중 사슬의 DNA 또는 RNA를 유전 물질로 포함하는 바이러스를 의미한다.In the present invention, the term bacteriophage refers to a bacterium-specific virus that infects a specific bacterium and inhibits and inhibits the growth of the bacterium, and includes a single or double-stranded DNA or RNA as a genetic material.

본 발명의 박테리오파지 ECOH1은 시가톡신 생성 대장균(Shiga toxin producing E. coli, STEC)에 대해 용균활성이 탁월하다. The bacteriophage ECOH1 of the present invention is excellent in the lytic activity against Shiga toxin producing E. coli (STEC).

본 발명의 박테리오파지 ECOH1은 189 내지 194 nm의 크기로, 정이십면체의 머리를 가지며 수축형 꼬리가 있는 형태인 마이오비리대(Myoviridae)에 속함을 확인하였으며, 단백질 패턴 분석 결과 90, 60, 50, 38, 32 및 18 kDa 크기의 주요 단백질을 포함한다. 또한 상기 박테리오파지 ECOH1은 열 및 pH에 대한 안정성이 우수하고, 세균 사멸능이 탁월하다는 특성을 가지고 있다.It was confirmed that the bacteriophage ECOH1 of the present invention belongs to the Myoviridae having a size of 189 to 194 nm and having a truncated sagittal head and a contraction tail, and the protein pattern analysis results showed that 90, 60, 50, 38, 32, and 18 kDa in size. In addition, the bacteriophage ECOH1 has excellent stability against heat and pH, and has an excellent bactericidal activity.

본 발명의 박테리오파지 ECOH1은 서열번호 1로 표시되는 염기서열을 전체 유전자의 전체 또는 일부로서 포함할 수 있다. 또한, 본 발명의 박테리오파지 ECOH1은 서열번호 1로 표시되는 염기서열, 및 상기 염기서열의 기능적 동등물로 이루어질 수 있다. 상기 기능적 동등물이란 염기서열의 변형, 치환의 결과, 상기 서열번호 1로 표시되는 염기서열과 적어도 70% 이상, 바람직하게는 80% 이상, 더욱 바람직하게는 90% 이상, 더더욱 바람직하게는 95% 이상의 서열 상동성을 갖는 것으로, 서열번호 1로 표시되는 염기서열과 실질적으로 동질의 생리활성을 나타내는 서열을 의미한다.The bacteriophage ECOH1 of the present invention may include the nucleotide sequence shown in SEQ ID NO: 1 as whole or a part of the entire gene. In addition, the bacteriophage ECOH1 of the present invention may consist of the nucleotide sequence shown in SEQ ID NO: 1 and the functional equivalent of the nucleotide sequence. The functional equivalent means at least 70% or more, preferably 80% or more, more preferably 90% or more, still more preferably 95% or more of the nucleotide sequence shown in SEQ ID NO: 1 as a result of modification or substitution of the nucleotide sequence. Or more and having substantially the same physiological activity as the nucleotide sequence shown in SEQ ID NO: 1.

상기와 같은 시가톡신 생성 대장균 특이적 용균활성, 내산성, 내염기성 및 내열성은 본 발명의 박테리오파지 ECOH1을 시가톡신 생성 대장균에 의한 감염성 질병의 예방 및 치료용 조성물, 및 상기 박테리오파지 ECOH1을 유효성분으로 포함하는 다양한 제품에 적용함에 있어, 다양한 온도 및 pH 범위의 적용이 가능하게 한다.The above-mentioned ciguatoxin-producing Escherichia coli-specific lytic activity, acid resistance, basic basicity and heat resistance can be obtained by a composition for preventing and treating infectious diseases caused by cytotoxin-producing Escherichia coli of the bacteriophage ECOH1 of the present invention and a composition containing the bacteriophage ECOH1 When applied to various products, it is possible to apply various temperature and pH ranges.

본 발명의 박테리오파지 ECOH1은 하수처리장 생물반응조, 도계장 및 양계농장 부근의 하수로부터 시료를 채취하여 분리한 박테리오파지로서, 박테리오파지 ECOH1로 명명하고 2017년 9월 13일에 한국미생물보존센터에 기탁번호 KFCC11731P로 기탁하였다.The bacteriophage ECOH1 of the present invention is a bacteriophage obtained by collecting a sample from a sewage treatment plant bioreactor, a slaughterhouse and a poultry farm, and named bacteriophage ECOH1, and deposited on September 13, 2017 with the deposit number KFCC11731P Respectively.

또한, 본 발명은 상기 박테리오파지 ECOH1을 포함하는, 항생용 조성물을 제공한다. In addition, the present invention provides an antibiotic composition comprising the bacteriophage ECOH1.

본 발명에서, 용어 항생용 조성물은 약제 형태로 동물에게 제공되어 균을 사멸시킬 수 있는 제제를 의미하며, 방부제, 살균제, 항생제 및 항균제를 총칭하는 것이다. In the present invention, the term antibiotic composition refers to a preparation which can be provided to an animal in the form of a drug to kill bacteria, and is collectively referred to as an antiseptic, a bactericide, an antibiotic and an antibacterial agent.

본 발명의 박테리오파지 ECOH1은 기존 항생제에 비하여 시가톡신 생성 대장균에 대한 특이성이 매우 높으므로, 유익균은 죽이지 않고, 특정 병원균만 사멸시킬 수 있고, 약물 내성 내지 저항성을 유도하지 않아, 기존의 항생물질에 비하여 제품수명(life cycling)이 긴 신규 항생제로서 이용될 수 있다.The bacteriophage ECOH1 of the present invention has a higher specificity to the ciguatoxin-producing E. coli than conventional antibiotics. Therefore, it is possible to kill only specific pathogens and not induce drug resistance or resistance, Can be used as a new antibiotic with a long life cycling.

또한, 본 발명은 상기 박테리오파지 ECOH1을 포함하는, 사료 첨가용 조성물을 제공한다.In addition, the present invention provides a composition for feed addition comprising the bacteriophage ECOH1.

양돈, 축산, 수산업, 반려동물 산업에서 사용되는 사료 첨가용 항생제는 질병의 예방 목적으로 사용되고 있는데, 예방 목적의 항생제 투여는 내성균 발생 가능성을 높이고 동물에 잔류하는 항생제가 사람에게 전달될 수 있어서 문제이다. 항생제가 육류를 통해 인체에 흡수되면 항생제 내성을 유발해 질병의 확산을 부를 수도 있다. 또한, 사료에 섞여 먹이는 항생제의 종류가 많고 이는 다제 내성균 발생 확률이 높아지는 문제점이 있기 때문에 좀 더 자연 친화적이면서도 기존의 항생제의 사용에서 발생한 문제를 해결할 새로운 사료 첨가용 항생물질로서 본 발명의 상기 박테리오파지 ECOH1을 이용할 수 있다.Feed antibiotics used in swine, livestock, fisheries and companion animal industries are used for the prevention of diseases. Antibiotic administration for prevention is problematic because it increases the possibility of resistant bacteria and antibiotics remaining in animals can be transmitted to humans . If antibiotics are absorbed into the body through meat, they may cause antibiotic resistance and spread the disease. In addition, since there are many types of antibiotics mixed with feed, there is a problem that the probability of occurrence of multidrug-resistant bacteria is increased. Therefore, as a new antibiotic substance for food addition, which is more environmentally friendly and solves problems caused by the use of existing antibiotics, Can be used.

또한, 본 발명은 상기 사료 첨가용 조성물을 포함하는 사료를 제공할 수 있으며, 본 발명의 사료는 박테리오파지를 사료 첨가제 형태로 따로 제조하여 사료에 혼합시키거나, 사료 제조 시 직접 첨가시켜 제조할 수 있다. 본 발명의 사료 내 박테리오파지는 액상 또는 건조 상태일 수 있으며, 바람직하게는 건조된 분말형태이다. 건조방법은 통풍건조, 자연건조, 분무건조 및 동결건조가 가능하지만, 이에 제한되는 것은 아니다. 본 발명의 박테리오파지는 분말형태로 사료 중량의 0.05 내지 10 중량%, 바람직하게는 0.1 내지 2 중량%의 성분비로 혼합될 수 있다. 또한, 상기 사료는 본 발명의 박테리오파지 외에 사료의 보존성을 높일 수 있는 통상의 첨가제들을 추가로 포함할 수 있다.In addition, the present invention can provide a feed comprising the feed composition, and the feed of the present invention can be prepared by separately preparing bacteriophage as a feed additive and mixing the feed into the feed, . The bacteriophage in the feed of the present invention may be in a liquid or dry state, preferably in the form of a dried powder. Drying methods include, but are not limited to, air drying, natural drying, spray drying and freeze drying. The bacteriophage of the present invention may be mixed in powder form in a composition ratio of 0.05 to 10% by weight, preferably 0.1 to 2% by weight of the feed weight. In addition to the bacteriophages of the present invention, the feed may further include conventional additives that can enhance the preservability of the feed.

본 발명의 사료 첨가용 조성물에는 비병원성의 다른 미생물이 추가로 첨가될 수 있다. 첨가될 수 있는 미생물로는 단백질 분해 효소, 지질 분해효소 및 당 전환 효소를 생산할 수 있는 바실러스 서브틸리스(Bacillus subtilis), 소의 위와 같은 혐기적 조건에서 생리적 활성 및 유기물 분해능이 있는 락토바실러스 균주(Lactobacillus sp.), 동물의 체중을 증가시키며 우유의 산유량을 늘리고 사료의 소화 흡수율을 높이는 효과를 보여주는 아스퍼질러스 오리자에(Aspergillus oryzae) 및 사카로미세스 세레비지에(Saccharomyces cerevisiae)로 구성된 군으로부터 선택될 수 있다.In the composition for feed addition of the present invention, microorganisms other than non-pathogenic microorganisms may be further added. Examples of microorganisms that can be added include Bacillus subtilis capable of producing proteolytic enzymes, lipolytic enzymes and glycosyltransferases, Lactobacillus strains having physiological activity and organic degradation ability under anaerobic conditions such as those above, sp.), increases the weight of the animal (Aspergillus in Aspergillus duck, showing the effect of increasing the milk production of the milk to increase the absorption of digested food party oryzae , and Saccharomyces cerevisiae .

본 발명의 박테리오파지 ECOH1을 포함하는 사료에는 식물성으로는 곡물류, 근과류, 식품가공 부산물류, 조류, 섬유질류, 제약 부산물류, 유지류, 전분류, 박류, 곡물부산물류 등이 있으며, 동물성으로는 단백질류, 무기물류, 유지류, 광물성류, 단세포 단백질, 동물성 플랑크톤류, 남은 음식물 등이 있으며 이에 제한되는 것은 아니다.The feedstuffs containing bacteriophage ECOH1 of the present invention include cereals, rootstocks, food processing busines, birds, fibers, pharmaceutical buses, oils, fats and oils, But are not limited to, proteins, mineralogy, oils, mineralogy, unicellular proteins, zooplankton, and remnants.

본 발명의 사료 첨가용 조성물에는 품질 저하를 방지하기 위하여 첨가하는 결착제, 유화제, 보존제 등이 포함될 수 있고, 효용 증대를 위하여 사료에 첨가하는 아미노산제, 비타민제, 효소제, 생균제, 향미제, 비단백태질소화합물, 규산염제, 완충제, 착색제, 추출제, 올리고당 등이 있으며, 그 외에도 사료 혼합제 등을 추가로 포함할 수 있다.The composition for feed addition of the present invention may contain a binder, an emulsifying agent, a preservative, etc. added to prevent deterioration of quality. An amino acid, a vitamin, an enzyme, a probiotic, a flavoring agent, A nitrogen compound, a silicate, a buffer, a coloring agent, an extracting agent, and an oligosaccharide. In addition, a feed mixture may be further included.

또한, 본 발명은 상기 박테리오파지 ECOH1을 포함하는, 소독제를 제공한다.The present invention also provides a disinfectant comprising the bacteriophage ECOH1.

시가톡신 생성 대장균에 특이적 사멸능을 갖는 본 발명의 박테리오파지 ECOH1을 포함하는 소독제는 병원감염을 막기 위한 병원 및 보건용의 소독제로 유용하게 사용될 수 있고 일반 생활 소독제, 식품 및 조리 장소 및 설비의 소독제, 양계장, 축사 등의 건물, 축체, 음수, 깔짚, 난좌, 운반차량, 식기 등의 각종 생육 용품의 소독 등에 사용될 수 있다.The disinfectant containing the bacteriophage ECOH1 of the present invention having a specific killing activity against the cytotoxin-producing E. coli can be effectively used as a disinfectant for hospital and public health to prevent hospital infection, and can be used as a disinfectant for general living disinfectants, foods, Disinfection of various kinds of growing equipment such as poultry houses, housing buildings such as pens, shaft bodies, water, litter, stairs, transportation vehicles, tableware, and the like.

또한, 본 발명은 상기 박테리오파지 ECOH1을 포함하는, 세척제를 제공한다.The present invention also provides a detergent comprising the bacteriophage ECOH1.

본 발명의 박테리오파지 ECOH1은 시가톡신 생성 대장균에 특이적 사멸능을 가지므로, 상기 시가톡신 생성 대장균에 노출되었거나 노출될 가능성이 있는 동물의 피부 표면 또는 신체 각 부위 등을 세척하는 용도로도 사용될 수 있다.Since the bacteriophage ECOH1 of the present invention has a specific killing effect on the cytotoxin-producing E. coli, the bacteriophage ECOH1 can also be used for washing the surface of the skin or parts of the body of an animal which is exposed or exposed to the above-mentioned cytotoxin-producing E. coli .

또한, 본 발명은 상기 박테리오파지 ECOH1을 개체에 투여하는 단계를 포함하는, 시가톡신 생성 대장균에 의한 감염성 질병의 예방 또는 치료 방법을 제공한다.The present invention also provides a method for preventing or treating an infectious disease caused by a cytotoxin-producing E. coli, which comprises the step of administering the bacteriophage ECOH1 to an individual.

본 발명의 방법은 시가톡신 생성 대장균에 의한 감염성 질병, 예컨대 세균성 식중독, 출혈성 대장염, 용혈성 요독증후군 또는 혈전성 혈소판 감소성 자반증이 발생한 개체에 박테리오파지 ECOH1을 투여하는 단계를 포함한다. The method of the present invention includes the step of administering bacteriophage ECOH1 to an infectious disease caused by cytotoxin-producing E. coli, such as bacterial food poisoning, hemorrhagic colitis, hemolytic uremic syndrome or thrombotic thrombocytopenic purpura.

본 발명에서, 용어 "개체"는 인간을 포함한 동물, 바람직하게는 인간, 가축류 또는 반려동물을 말하며, 이에 제한되는 것은 아니다.In the present invention, the term "individual" refers to an animal, including a human, preferably a human, livestock or companion animal, but is not limited thereto.

상기 용어 "가축류"는 인간에 의하여 순화, 개량되어 인간과 함께 공동생활을 하는 유용한 동물을 지칭하는 개념으로, 조류, 어류, 곤충류, 포유류를 모두 포함하는 개념이며, 상기 가축류는 돼지, 소, 닭, 말, 오리 및 개로 구성된 군에서 선택될 수 있으나, 이에 제한되는 것은 아니다.The term "livestock" is a concept that refers to useful animals that are refined and improved by humans to co-live with humans, including birds, fishes, insects, and mammals. The livestock are pigs, , Horse, duck, and dog, but is not limited thereto.

본 발명의 방법에서 상기 박테리오파지 ECOH1 또는 조성물은 약학적 제제의 형태로 동물에게 투여되거나, 개체의 사료 또는 음용수에 혼합하여 이를 섭식시키는 방법을 통해 투여될 수 있다.In the method of the present invention, the bacteriophage ECOH1 or the composition may be administered to an animal in the form of a pharmaceutical preparation, or mixed with feed or drinking water of an individual and fed.

본 발명의 방법에서 상기 박테리오파지 ECOH1 또는 조성물의 투여 경로는 목적 조직에 도달할 수 있는 한 경구 또는 비경구의 다양한 경로를 통하여 투여될 수 있으며, 구체적으로, 구강, 직장, 국소, 정맥 내, 복강 내, 근육 내, 동맥 내, 경피, 비측 내, 흡입 등을 통해 통상적인 방식으로 투여될 수 있다.In the method of the present invention, the administration route of the bacteriophage ECOH1 or the composition can be administered through various routes of oral or parenteral administration as long as it can reach the target tissues. Specifically, oral administration, rectal administration, topical administration, intravenous, Intravenous, intramuscular, intraarterial, transdermal, intranasal, inhalation, and the like.

본 발명의 방법에 투여되는 상기 박테리오파지 ECOH1의 적합한 총 1일 사용량은 올바른 의학적 판단범위 내에서 처치의에 의해 결정될 수 있다는 것은 당업자에게 자명한 일이다. 특정 개체에 대한 구체적인 치료적 유효량은 달성하고자 하는 반응의 종류와 정도, 환자의 연령, 체중, 일반 건강 상태, 성별 및 식이, 투여시간, 투여 경로 및 조성물의 분비율, 치료기간, 구체적 조성물과 함께 사용되거나 동시 사용되는 약물을 비롯한 다양한 인자와 의약 분야에 잘 알려진 유사 인자에 따라 다르게 적용하는 것이 바람직하다.It will be apparent to those skilled in the art that the appropriate total daily dose of the bacteriophage ECOH1 administered to the method of the present invention may be determined by treatment within the scope of sound medical judgment. The specific therapeutically effective amount for a particular individual will depend upon the type and extent of the response to be achieved, the age, weight, general health, sex and diet of the patient, the time of administration, the route of administration and the fraction of the route of administration, It is preferable to apply differently depending on various factors including drugs used or co-used and similar factors well known in the medical field.

본 명세서에서 달리 정의되지 않은 용어들은 본 발명이 속하는 기술분야에서 통상적으로 사용되는 의미를 갖는 것이다.Terms not otherwise defined herein have meanings as commonly used in the art to which the present invention belongs.

이하, 실시예를 통하여 본 발명을 더욱 상세히 설명하고자 한다. 이들 실시예는 오로지 본 발명을 예시하기 위한 것으로서, 본 발명의 범위가 이들 실시예에 의해 제한되는 것으로 해석되지는 않는 것은 당업계에서 통상의 지식을 가진 자에게 있어서 자명할 것이다.Hereinafter, the present invention will be described in more detail with reference to Examples. It is to be understood by those skilled in the art that these examples are for illustrative purposes only and that the scope of the present invention is not construed as being limited by these examples.

실시예Example 1.  One. 신규한New 박테리오파지의 분리 및 배양 Isolation and culture of bacteriophage

1-1. 박테리오파지의 스크리닝 및 단일 박테리오파지의 분리1-1. Screening of bacteriophages and isolation of single bacteriophages

대장균 O157:H7에 특이적인 박테리오파지를 스크리닝 및 분리하기 위해서 반점 용균반 분석을 수행하였다. 시료는 박테리오파지가 존재할 것으로 예상되는 하수처리장 생물반응조, 도계장 및 양계농장 부근의 하수로부터 시료를 채취하였으며, 박테리오파지 분리에 사용된 대장균 O157:H7은 (주)옵티팜에서 분리 및 동정한 균주를 사용하였다.Bacterial plaque assay was performed to screen and isolate E. coli O157: H7 specific bacteriophages. Samples were collected from sewage treatment plant bioreactors, slaughterhouses and poultry farms where bacteriophages are expected to be present, and E. coli O157: H7 used for bacteriophage isolation was isolated and identified from Opti Pharm Co., Ltd. .

구체적으로, 채취한 시료를 균질화 한 후 대장균 O157:H7과 함께 35℃에서 하룻밤 동안 진탕배양 하였다. 상기 배양액을 4,000 rpm으로 20분간 원심분리한 후, 상등액을 공극(pore) 크기가 0.2 μm인 필터를 이용하여 여과하여 시료 여과액을 얻었다. Specifically, the collected sample was homogenized and incubated with E. coli O157: H7 at 35 占 폚 overnight with shaking. The culture was centrifuged at 4,000 rpm for 20 minutes, and the supernatant was filtered using a filter having a pore size of 0.2 μm to obtain a sample filtrate.

전배양된 대장균 O157:H7 150 μL을 취해서 멸균된 튜브에 넣고, 3 mL의 LB 탑 아가[LB 배지(트립톤 10 g/L, 효모 추출물(yeast extract) 5 g/L, NaCl 10 g/L) + 0.6% 아가]를 첨가하여 잘 혼합한 후 미리 만들어 둔 LB 아가 플레이트에 중층하였다. 실온에서 30분간 방치한 후 준비된 샘플 여과액을 각각 10 uL씩 점적한 후 실온에서 30분 동안 방치하였고, 이를 35℃에서 하룻밤 동안 배양한 후 박테리오파지의 유무를 확인하였다.150 μL of pre-cultured E. coli O157: H7 was placed in a sterilized tube and 3 mL of LB topa agar [LB medium (10 g / L of tryptone, 5 g / L of yeast extract, 10 g / L of NaCl ) + 0.6% agar] was added thereto, and the mixture was well mixed and then layered on the previously prepared LB agar plate. After incubation at room temperature for 30 minutes, 10 μL of the prepared sample filtrate was added to each well, and the mixture was allowed to stand at room temperature for 30 minutes. After incubation at 35 ° C. overnight, bacteriophage was observed.

박테리오파지의 존재를 확인한 시료로부터 박테리오파지를 순수 분리하기 위해서 소프트 아가 오버레이(soft agar overlay)법을 이용하였다. 박테리오파지가 존재하는 것으로 확인된 시료를 식염수로 적절히 희석하여 각 희석단의 시료 희석액 100 μL를 취하고, 대상 세균(대장균 O157:H7) 배양액 150 μL에 혼합한 후 0.6% LB 탑 아가 3 mL을 첨가하여 잘 혼합한 뒤, 미리 만들어 둔 2% LB 아가 플레이트에 중층하여 방치한 후 35℃에서 24시간 배양하였다. 배양한 각 플레이트에서 형성된 용균반을 확인한 후, 이를 선택하여 400 μL의 SM 완충액 (NaCl 5.8 g/L; MgSO47H2O 2 g/L; 1M Tris-HCl (pH7.5) 50 mL)에 현탁하고, 실온에서 4시간 동안 방치하였다. 상기 박테리오파지액 100 μL를 0.6% LB 탑 아가가 포함된 세균 배양액 500 μL와 혼합한 뒤 150 mm 지름의 LB 플레이트에 분주하여 중층한 후 완전히 용균이 일어날 때까지 35℃에서 배양하였다. 배양이 종료된 후, LB 플레이트에 15 mL의 SM 완충액을 가하고 실온에서 4시간 동안 천천히 교반하면서 박테리오파지 용액을 회수한 후 4,000 rpm으로 20분간 원심분리하여 상등액만 취하고 이를 0.45 μm 필터로 여과하여 최종 박테리오파지 용액을 회수하였다. 이렇게 얻어진 최종 박테리오파지의 용균반을 확인한 결과를 도 1에 나타내었다.A soft agar overlay method was used to isolate the bacteriophage from the sample which confirmed the existence of the bacteriophage. A sample of which the bacteriophage was confirmed to be present was diluted appropriately with saline, 100 μL of sample dilution at each dilution stage was taken, mixed with 150 μL of the bacterial culture (E. coli O157: H7), and 3 mL of 0.6% LB topa After well mixing, the mixture was allowed to stand in a 2% LB agar plate which had been previously prepared, and then incubated at 35 ° C for 24 hours. After culturing, the plate was selected, and 400 μL of SM buffer solution (NaCl 5.8 g / L; MgSO 4 7H 2 O 2 g / L; 1M Tris-HCl (pH 7.5) 50 mL) was added to each plate Suspended and allowed to stand at room temperature for 4 hours. 100 .mu.L of the bacteriophage solution was mixed with 500 .mu.L of a bacterial culture solution containing 0.6% LB top agar, and the mixture was divided into 150-mm-diameter LB plates and cultured at 35.degree. After completion of the incubation, 15 mL of SM buffer was added to the LB plate, and the bacteriophage solution was recovered while slowly stirring at room temperature for 4 hours. Then, the supernatant was centrifuged at 4,000 rpm for 20 minutes to filter out the supernatant. The solution was recovered. FIG. 1 shows the result of checking the thus obtained final bacteria bacterium.

도 1에 나타낸 바와 같이, 2 내지 3 mm의 크기를 가지는 용균반을 형성하는 박테리오파지를 확인하였고, 상기 박테리오파지는 대장균 O157:H7에 특이적인 용균능을 갖는 박테리오파지임을 확인하였다.As shown in Fig. 1, a bacteriophage forming a fungus having a size of 2 to 3 mm was confirmed, and it was confirmed that the bacteriophage was a bacteriophage having a solubility specific to E. coli O157: H7.

1-2. 박테리오파지의 대량 배양 및 정제1-2. Bulk culture and purification of bacteriophages

상기 실시예 1-1에서 확인한 대장균 O157:H7 특이적 박테리오파지를 대량 배양하기 위하여, 실시예 1-1에서 회수한 최종 박테리오파지 배양액을 1.0x107 PFU/mL로 희석한 후 전배양된 대장균 O157:H7 1.0x109 CFU/mL과 혼합하여 MOI(Multiplicity of infection)가 0.01이 되도록 35℃에서 120 rpm으로 9시간 동안 배양하였다. 배양이 종료된 후 배양액 전량을 6,000 rpm으로 30분간 원심분리하여 상등액을 수득하였고, 이를 0.2 μm 필터로 여과하여 최종 박테리오파지 배양액을 회수하였다. 분리된 박테리오파지를 "박테리오파지 ECOH1(Bacteriophage ECOH1)"로 명명하고, 2017년 9월 13일 한국미생물보존센터(Korean Culture Center of Microorganisms, 서울, 한국)에 기탁하여 기탁번호 KFCC11731P를 부여받았다.In order to mass-culture the E. coli O157: H7 specific bacteriophage identified in Example 1-1, the final bacteriophage culture recovered in Example 1-1 was diluted to 1.0 x 10 7 PFU / mL, and the pre-cultured E. coli O157: H7 1.0 × 10 9 CFU / mL and cultured at 35 ° C. and 120 rpm for 9 hours so that the MOI (multiplicity of infection) was 0.01. After the culture was completed, the whole culture was centrifuged at 6,000 rpm for 30 minutes to obtain a supernatant, which was then filtered with a 0.2 μm filter to recover the final bacteriophage culture. Separated bacteriophages were named as "Bacteriophage ECOH1" and deposited with the Korean Culture Center of Microorganisms (Seoul, Korea) on September 13, 2017, and received the deposit number KFCC11731P.

실시예Example 2. 박테리오파지  2. Bacteriophage ECOH1의Of ECOH1 전체 유전자 분석 Whole gene analysis

박테리오파지 ECOH1의 전체 유전자를 분석하기 위해, 박테리오파지 ECOH1 배양액에 20 mM EDTA, 50 μg/mL의 프로테나아제 K, 0.5%(w/v) SDS를 가한 후, 50℃에서 1시간 동안 정치하였다. 동량의 페놀-클로로포름-이소프로필 알코올(25:24:1)과 혼합한 후 실온에서 12,000 rpm으로 10분간 원심분리하여 상등액 회수하였다. 회수된 상등액을 동일 부피의 페놀-클로로포름-이소프로필 알코올(25:24:1)과 혼합하여 실온에서 12,000 rpm으로 10분간 원심분리한 후 상등액 회수하고, 상기 상등액에 3M 소듐 아세테이트를 전체 부피의 10%(v/v)가 되도록 가한 후 혼합하였다. 여기에 2배 부피의 차가운 95% 에탄올을 가하여 혼합한 뒤 -20℃에서 1시간 동안 정치하였다. 반응이 끝난 후 0℃에서 10분간 12,000 rpm으로 원심분리하여 침전물 획득하였고, 차가운 70% 에탄올로 2회 세척한 뒤 에탄올을 완전히 제거하여 DNA 펠렛을 회수하였다. 회수한 펠렛을 최종 부피가 50 μL이 되도록 TE 완충액 (Tris-EDTA, pH8.0)에 용해시킨 후 DNA 농도를 측정하였다. 전체 유전자 분석을 위해 PacBioRSII를 이용하여 유전자 시퀀싱을 시행하였다(마크로젠, 한국). 시퀀싱 결과로 얻은 박테리오파지 ECOH1의 유전자 맵은 도 2에 나타내었다.To analyze the entire gene of bacteriophage ECOH1, 20 mM EDTA, 50 μg / mL proteinase K and 0.5% (w / v) SDS were added to the bacteriophage ECOH1 culture medium and left at 50 ° C. for 1 hour. The mixture was mixed with an equal amount of phenol-chloroform-isopropyl alcohol (25: 24: 1) and centrifuged at 12,000 rpm for 10 minutes at room temperature to recover the supernatant. The recovered supernatant was mixed with an equal volume of phenol-chloroform-isopropyl alcohol (25: 24: 1) and centrifuged at 12,000 rpm for 10 minutes at room temperature. The supernatant was recovered and 3M sodium acetate was added to the supernatant in a total volume of 10 % (v / v). The mixture was mixed with 2 volumes of cold 95% ethanol, and the mixture was allowed to stand at -20 DEG C for 1 hour. After the reaction was completed, the precipitate was collected by centrifugation at 12,000 rpm for 10 minutes at 0 ° C., washed twice with cold 70% ethanol, and then the ethanol was completely removed to recover the DNA pellet. The recovered pellet was dissolved in TE buffer (Tris-EDTA, pH 8.0) to a final volume of 50 μL, and the DNA concentration was measured. Gene sequencing was performed using PacBioRSII for whole gene analysis (Macrogen, Korea). The gene map of bacteriophage ECOH1 obtained as a result of sequencing is shown in Fig.

도 2에 나타낸 바와 같이, 박테리오파지 ECOH1의 전체 유전자의 크기는 78,384 bp이며, GC함량이 39%, 전체 ORFs의 수는 103개임을 확인하였다. 분석한 박테리오파지 ECOH1의 전체 유전자 서열을 서열번호 1로 나타내었다. As shown in FIG. 2, it was confirmed that the size of the entire gene of bacteriophage ECOH1 was 78,384 bp, the GC content was 39%, and the total number of ORFs was 103. The entire gene sequence of the analyzed bacteriophage ECOH1 is shown in SEQ ID NO: 1.

실시예Example 3. 박테리오파지  3. Bacteriophage ECOH1의Of ECOH1 형태학적 특성 Morphological characteristics

박테리오파지 ECOH1의 형태학적 특성을 알아보기 위해, 박테리오파지 ECOH1의 순수배양액을 0.01% 젤라틴 용액에 희석하여 2.5% 글루타르알데하이드(glutaraldehyde) 용액으로 고정하였다. 이를 탄소-코팅 운모 플레이트(carbon-coated mica plate(ca. 2.5 x 2.5 mm))에 적가한 후, 10분간 적응시킨 후 멸균증류수로 세척하였다. 이를 구리 격자(copper grid)에 끼워 2% 우라닐 아세테이트(Uranyl acetate)에서 30 내지 60초 동안 염색하고 건조시킨 후, 투과전자현미경(Tecnai G2 Spirit Twin, Bio-Transmission electron microscope, 120 kV, 120,000~400,000)으로 검경하였으며, 그 결과를 도 3에 나타내었다.To determine the morphological characteristics of bacteriophage ECOH1, the pure culture of bacteriophage ECOH1 was diluted in 0.01% gelatin solution and fixed with 2.5% glutaraldehyde solution. This was applied to a carbon-coated mica plate (ca. 2.5 x 2.5 mm), followed by a 10-minute adaptation and washing with sterile distilled water. The resultant was stained with 2% Uranyl acetate for 30 to 60 seconds, and dried using a transmission electron microscope (Tecnai G2 Spirit Twin, Bio-Transmission electron microscope, 120 kV, 400,000), and the results are shown in FIG.

도 3에 나타낸 바와 같이, 박테리오파지 ECOH1은 전체 길이 189 내지 194 nm의 크기로, 정이십면체의 머리를 가지며 수축성 꼬리가 있는 형태인 마이오비리대(Myoviridae)에 속함을 확인하였다.As shown in Fig. 3, bacteriophage ECOH1 was found to belong to Myoviridae, which is 189-194 nm in total length, and has a truncated dichroic head with a contractile tail.

실시예Example 4. 박테리오파지  4. Bacteriophage ECOH1의Of ECOH1 단백질 패턴 분석 Protein pattern analysis

박테리오파지 ECOH1의 단백질 패턴을 분석하기 위해, 1.0x1010 PFU/mL로 준비된 박테리오파지 ECOH1 40 μL를 10 μL의 5X 로딩 완충액과 혼합하고, 10분간 끓인 다음 12.5% SDS-PAGE를 수행하였다. SDS-PAGE 수행 후 단백질 전기영동 결과를 도 4에 나타내었다.To analyze the protein pattern of bacteriophage ECOH1, 40 μL of bacteriophage ECOH1 prepared to 1.0 × 10 10 PFU / mL was mixed with 10 μL of 5X loading buffer, boiled for 10 minutes, and then subjected to 12.5% SDS-PAGE. The results of SDS-PAGE and protein electrophoresis are shown in FIG.

도 4에 나타낸 바와 같이, 박테리오파지 ECOH1은 90, 60, 50, 38, 32 및 18 kDa 크기의 주요 단백질을 가지는 것을 확인하였다.As shown in FIG. 4, it was confirmed that bacteriophage ECOH1 has 90, 60, 50, 38, 32 and 18 kDa major proteins.

실시예Example 5. 박테리오파지  5. Bacteriophage ECOH1의Of ECOH1 다양한 세균에 대한 감염성 조사 Investigation of infectivity against various bacteria

박테리오파지 ECOH1이 다양한 세균에 대하여 용균활성을 나타내는지 확인하기 위하여 ㈜옵티팜에서 분리하여 보유하고 있는 균주와 미생물 자원센터 등에서 분양받은 균주를 대상으로 소프트 아가 오버레이법을 통해서 감염성을 확인하였다. 그 결과를 표 1에 나타내었다.In order to confirm whether bacteriophage ECOH1 exhibits lytic activity against various bacteria, the strains isolated from OptiParm Co., Ltd. and purchased from the microorganism resource center were examined for infectivity through soft agar overlay method. The results are shown in Table 1.

Figure pat00001
Figure pat00001

표 1에 나타낸 바와 같이, 대장균 및 다른 미생물을 대상으로 감수성 검사를 진행한 결과, 박테리오파지 ECOH1은 장관출혈성 대장균인 O157:H7 및 시가톡신 생성 대장균(STEC)에 대해서 용균활성을 나타내는 것을 확인하였다. 그러나, 비병원성 대장균, Salmonella Typhimurium, Bacillus cereus, Listeria monocytogenes, Lactobacillus plantarum 등에는 용균활성이 없는 것을 확인하였다. As shown in Table 1, the susceptibility test of E. coli and other microorganisms showed that bacteriophage ECOH1 exhibited lytic activity against O157: H7 and E. coli producing stigma E. coli (STEC). However, non-pathogenic Escherichia coli, Salmonella Typhimurium , Bacillus cereus , Listeria monocytogenes, Lactobacillus plantarum And the like.

따라서, 본 발명의 박테리오파지 ECOH1은 시가톡신 대장균(STEC)에 특이적으로 용균활성을 나타내는 박테리오파지임을 확인하였다.Therefore, it was confirmed that the bacteriophage ECOH1 of the present invention is a bacteriophage exhibiting a lytic activity specifically to the cigatoxin E. coli (STEC).

실시예Example 6. 박테리오파지  6. Bacteriophage ECOH1의Of ECOH1 pH 안정성 조사 pH stability investigation

박테리오파지 ECOH1의 pH 안정성을 확인하기 위하여, 다양한 pH 범위 (pH2, 3, 4, 5, 6, 7, 8, 9, 10, 11)에서 박테리오파지의 수를 측정하였다. 소듐 아세테이트 완충액, 소듐 포스페이트 완충액, Tris-HCl을 이용하여 각각의 pH에 맞게 조제한 후 1 mL로 분주하여 준비하였다. 1.0x108 PFU/mL로 준비한 박테리오파지 ECOH1 배양액 10 μL을 상기 용액에 첨가하여 2시간 동안 상온에서 방치하였다. 방치 후 각 반응액을 단계 희석하여 소프트 아가 오버레이법에 의한 타이터(titer) 측정을 수행한 결과를 도 5에 나타내었다.The number of bacteriophages was measured in various pH ranges (pH 2, 3, 4, 5, 6, 7, 8, 9, 10, 11) to confirm the pH stability of bacteriophage ECOH1. Sodium acetate buffer, sodium phosphate buffer, and Tris-HCl were added to each pH-adjusted solution, and the mixture was divided into 1 mL. 10 μL of the bacteriophage ECOH1 culture prepared to 1.0 × 10 8 PFU / mL was added to the solution, and left at room temperature for 2 hours. After allowing to stand, each reaction solution was diluted stepwise, and a titer measurement was performed by soft agar overlay method. The result is shown in FIG.

도 5에 나타낸 바와 같이, 박테리오파지 ECOH1은 pH4 내지 11의 범위에서 2시간 동안 안정한 것을 확인하였다. 따라서, 박테리오파지 ECOH1은 pH 안정성이 우수한 박테리오파지임을 알 수 있다.As shown in Fig. 5, it was confirmed that the bacteriophage ECOH1 was stable for 2 hours in the range of pH 4 to 11. Therefore, it can be seen that bacteriophage ECOH1 is a bacteriophage having excellent pH stability.

실시예Example 7. 박테리오파지  7. Bacteriophage ECOH1의Of ECOH1 열 안정성 조사 Thermal stability investigation

박테리오파지 ECOH1의 열 안정성을 확인하기 위하여, 다양한 온도 범위 (40℃, 50℃, 60℃, 70℃)에서 박테리오파지의 수를 측정하였다. 박테리오파지 ECOH1 배양액 (1.0x108 PFU/mL) 5 mL을 멸균된 튜브에 분주한 후 박테리오파지를 첨가하여 2시간 동안 각 온도에서 방치하였다. 방치 후 각 반응액을 단계희석하여 소프트 아가 오버레이법에 의한 타이터 측정을 수행한 결과를 도 6에 나타내었다.In order to confirm the thermal stability of bacteriophage ECOH1, the number of bacteriophages was measured in various temperature ranges (40 ° C, 50 ° C, 60 ° C, 70 ° C). 5 mL of bacteriophage ECOH1 culture (1.0 x 10 8 PFU / mL) was dispensed into sterile tubes and bacteriophage was added and left at each temperature for 2 hours. After allowing to stand, each reaction solution was diluted stepwise, and the result of performing a tester measurement by soft agar overlay method is shown in FIG.

도 6에 나타낸 바와 같이, 박테리오파지 ECOH1은 40 내지 50℃의 범위에서 60분까지 안정한 것을 확인하였다. 따라서 상기 박테리오파지 ECOH1은 내열성이 우수한 박테리오파지임을 알 수 있다.As shown in Fig. 6, it was confirmed that the bacteriophage ECOH1 was stable up to 60 minutes in the range of 40 to 50 占 폚. Therefore, it can be seen that the bacteriophage ECOH1 is a bacteriophage having excellent heat resistance.

실시예Example 8. 박테리오파지  8. Bacteriophage ECOH1의Of ECOH1 세균  Germ 사멸능Destructiveness 조사 Research

박테리오파지 ECOH1의 세균 사멸능을 확인하기 위하여, 배양 시간에 따른 세균의 배양 상태를 조사하였다. 구체적으로, 600 nm에서 흡광도가 0.5인 세균 배양액(대장균 O157:H7) 10 mL을 준비하였다. 상기 세균 배양액에 1.0x1010 PFU/mL의 박테리오파지 ECOH1 배양액 1 mL을 첨가하여 MOI(Multiplicity of infection)가 10이 되도록 접종하였다(실험군 1). 박테리오파지 ECOH1이 접종된 세균 배양액을 3 시간 동안 배양하였으며, 1 시간 단위로 파장 600 nm에서의 흡광도를 측정하였다.In order to confirm the bactericidal activity of bacteriophage ECOH1, culture conditions of bacteria were examined according to incubation time. Specifically, 10 mL of a bacterial culture solution (E. coli O157: H7) having an absorbance of 0.5 at 600 nm was prepared. 1 ml of 1.0 × 10 10 PFU / ml bacteriophage ECOH1 culture was added to the bacterial culture to inoculate MOI (multiplicity of infection) of 10 (experimental group 1). The bacterial culture inoculated with bacteriophage ECOH1 was incubated for 3 hours, and the absorbance at 600 nm was measured in an hour.

실험군 2는 실험군 1과 동일하게 세균 사멸능을 조사하되, 세균 배양액에 1.0x109 PFU/mL의 박테리오파지 ECOH1 배양액 1 mL을 첨가하여 MOI가 1이 되도록 접종하였다. 대조군은 박테리오파지 ECOH1 배양액을 첨가하지 않은 세균 배양액을 사용하였다. 박테리오파지 ECOH1의 세균 사멸능 조사 결과는 표 2에 나타내었다.Experimental group 2 was inoculated with 1 × 10 9 PFU / mL of bacteriophage ECOH1 culture solution to the bacterial culture, and MOI of 1 was inoculated. As a control group, a bacterial culture solution to which no bacteriophage ECOH1 culture medium was added was used. The results of the bacteriocidal activity of bacteriophage ECOH1 are shown in Table 2.

Figure pat00002
Figure pat00002

표 2에 나타낸 바와 같이, 박테리오파지 ECOH1을 첨가한 실험군 1 및 2는 대조군보다 흡광도가 낮게 측정되었다. 상기 결과는 대장균 O157:H7에 대한 박테리오파지 ECOH1의 사멸능이 우수함을 의미한다.As shown in Table 2, the experimental groups 1 and 2 to which bacteriophage ECOH1 was added had lower absorbance than the control group. This result means that the killing effect of bacteriophage ECOH1 against E. coli O157: H7 is excellent.

종합적으로 본 발명자들은 박테리오파지 ECOH1가 시가톡신 생성 대장균에 대한 특이성이 매우 높고, 시가톡신 생성 대장균에 감염하여 시가톡신 생성 대장균 내에서 증식함으로써 용균 활성이 우수하며, 물리화학적 자극에 강하다는 장점을 가지고 있음을 확인하였다. 또한 본 발명의 박테리오파지 ECOH1은 사람, 동물, 식물 등 세균 외의 다른 숙주에는 감염되지 않으므로, 항생제의 오남용으로 인한 항생제 내성균의 문제점, 식품 내의 항생제의 잔류문제, 광범위한 숙주범위의 문제점을 해결할 수 있는 장점이 있다. 따라서 본 발명의 박테리오파지 ECOH1은 항생용 조성물, 사료첨가용 조성물, 사료, 소독제 또는 세척제 분야에서 다양하게 활용될 수 있다.Taken together, the inventors of the present invention have the advantage that bacteriophage ECOH1 is highly specific for the cytotoxin-producing Escherichia coli, has an excellent lytic activity by being infected with the cytotoxin-producing Escherichia coli and proliferating in the cytotoxin-producing Escherichia coli, and is resistant to physicochemical stimulation Respectively. In addition, the bacteriophage ECOH1 of the present invention is not infected with any host other than bacteria such as human, animal, and plant. Therefore, it is possible to solve problems of antibiotic resistant bacteria caused by abuse of antibiotics, residual antibiotics in food, have. Therefore, the bacteriophage ECOH1 of the present invention can be utilized in various fields in antibiotic composition, composition for feed addition, feed, disinfectant or detergent.

이하, 제제예를 통하여 본 발명을 더욱 상세히 설명하고자 한다. 제제예는 오로지 본 발명을 예시하기 위한 것으로서, 본 발명의 범위가 제제예에 의해 제한되는 것으로 해석되지 않는다.Hereinafter, the present invention will be described in more detail with reference to formulation examples. The formulation examples are for illustrating the present invention only, and the scope of the present invention is not construed as being limited by formulation examples.

제제예Formulation example 1. 사료 첨가용 조성물 1. Composition for Feed Additive

박테리오파지 ECOH1 1x107 PFU/mLBacteriophage ECOH1 1x10 7 PFU / mL

비타민 믹스 100 mgVitamin mix 100 mg

미네랄 믹스 100 mgMineral mix 100 mg

스테아린산 마그네슘 2 mgMagnesium stearate 2 mg

통상의 사료 첨가제 제조방법에 따라 상기의 성분들을 혼합하여 제조한다.The above components are mixed and prepared according to a conventional feed additive manufacturing method.

제제예Formulation example 2. 소독제 조성물 2. Disinfectant composition

박테리오파지 ECOH1 1x107 PFU/mLBacteriophage ECOH1 1x10 7 PFU / mL

에탄올 적량Ethanol quantity

멸균 증류수 적량Sterilized distilled water suitable amount

pH 조절제 적량pH adjuster

통상의 소독제 제조방법에 따라 상기의 성분들을 혼합하여 제조한다.The above components are mixed and prepared according to a conventional disinfectant preparation method.

제제예Formulation example 3. 세척제 조성물 3. Cleaner composition

박테리오파지 ECOH1 1x107 PFU/mLBacteriophage ECOH1 1x10 7 PFU / mL

에탄올 적량Ethanol quantity

효소 복합물 적량Enzyme complex

멸균 증류수 적량Sterilized distilled water suitable amount

통상의 세척제 제조방법에 따라 상기의 성분들을 혼합하여 제조한다.The above components are mixed and prepared according to a conventional method for producing a detergent.

이상, 본 발명내용의 특정한 부분을 상세히 기술하였는바, 당업계의 통상의 지식을 가진 자에게 있어서, 이러한 구체적인 기술은 단지 바람직한 실시양태일 뿐이며, 이에 의해 본 발명의 범위가 제한되는 것이 아닌 점은 명백할 것이다. 따라서 본 발명의 실질적인 범위는 첨부된 청구항들과 그것들의 등가물에 의해 정의된다고 할 것이다. Having described specific portions of the present invention in detail, those skilled in the art will appreciate that these specific embodiments are merely preferred embodiments and that the scope of the present invention is not limited thereby. something to do. Accordingly, the actual scope of the present invention will be defined by the appended claims and their equivalents.

한국미생물보존센터Korea Microorganism Conservation Center KFCC11731PKFCC11731P 2017091320170913

<110> Optipharm.CO.,LTD <120> Novel shiga toxin producing Escherichia coli specific bacteriophage ECOH1 and antibacterial composition comprising the same <130> 1-65P <160> 1 <170> KoPatentIn 3.0 <210> 1 <211> 78384 <212> DNA <213> Unknown <220> <223> Bacteriophage ECOH1 <400> 1 agagatgccc cttaacattt tcttaacaat ttcttaacaa tccctacata gttatgcttt 60 taaggcactt gttagagact tgttagcccc ttgttaaatc tctgttaaga ccacgtaaaa 120 gccttgtaag agtctttagc atagccttta aagcctctgt aaagctctat aaagaggtat 180 ctatacagtt ggggtgtaat tctaggaaga gacttaaaag agcttacaag gagctataga 240 gagcttttaa gagggctatt tagagaatca ctaagaggga aagggaacga taaggaagag 300 atagtgacca tgttaatagc ttgttaaaaa gattaaacac ttgttagaaa cttattaatt 360 accttaacaa aataactctt aaaaattaac ttgttagctc ttgttagtca tctgttaaga 420 ttctgtaaag cactatcaag ccttgttaag aaactgttac gttcttgtta gttatgttaa 480 gaatctgtta agacctttgg agagttgtta agaagatgtg agaactgtta agagattgtt 540 aaggatattt taaaattttg caaagggggt gttaaggagc tgttaagggc taccaagcag 600 atatacatcc tagacagata tttttcagtt ccttcaaaga ccctaaaaaa tgacttgata 660 gtcctatttt ataaaaattt taagattctg aataattacc tagacagtct tttaaaaata 720 caggcataaa caggcttata agataccttg ttagtaccgt gttagacctt gtgagataag 780 gtctgtaaag atattcctgt taagtttgtt aaaacagtct atatagaggc ttagtagtgc 840 ctagtgaaca cctatagaga gtatcatagc tgacatagag attaaggggt gtatagaggc 900 ttctaagagc gtatagagag atggttaagg tgattgtata ggttgttaag atggcttgtt 960 agaagagtgt ttagaaggct tattaaaggg ctatttagaa gggttataca gaggggctat 1020 taagaccact agatagttac taagatacta tatagtatta tataactata tagagagtaa 1080 gattaagaag gttgttaaga aggatagata ttttattcac atatgatggt gacccagagg 1140 ttgggacaac cgataaaatt ttataaaaat taaaaagccc ccaattaagg aggctcttaa 1200 gatattttaa atcagtgttt ccagaactgt ttttagtgat gacttggttg tctgataaaa 1260 atgagtaaag ccattgttgt tatcaaatac ctgcatcatg atatcatctc ccttgattgg 1320 gtacactcgg atatcatagt ggaaaccatt aaagacacaa gagccattac agaatgcact 1380 aaagtcatcc actgagatat actcttcatg tcctgtgatt tttatacaga tacctttact 1440 cggtctctta ggattaatat cttccatcac agacatattc tgtccaccaa gagataccat 1500 agtgaccact ttacggttct tctgtttaaa gtacatctta actttctgca aagtgtcttc 1560 atagaacgga taagacttct ctacaaagat tccttcaagt ggctctttac cattttcaac 1620 ttctctggta tgccgtactg caaagataat ttgttggaac cagtcaagat tttcttcgga 1680 gagtgcttct cgaacatcac tccagtcaag aactaggtag ttgccttcaa cttcttttaa 1740 gttatctttt tccatatcta tcacaccatt atcgtaaaac ttggtaagct ggtactgcaa 1800 acttgttgct attgttccta ataaggtctt cttctgttac taagaatgta atcccacata 1860 agtgcgtata gtggctgtca tactcaaata ttttaagtaa gtatttacca tcatgataaa 1920 cagattctac tacacctttt gcaacaatct ttccagtctt gaagtcttta agagggtatg 1980 tattaccaac tttagggact gttttcactt caggttcttt tagcttctca ctagcttcta 2040 catcacctag taagttagaa ctttcaaaag ctctgaatct catataagct tctgaacatt 2100 cccagataaa acaatgtaca agaaccttag cagcatgtct tgagcaattc aactcatcac 2160 agatttcttt gtacatttca tctttagttg aattggtaag cattgctttt cgaactgttt 2220 ctttaatttt cataagctct ccgaataacc ctattaagca tctctaaagt cagctttcca 2280 gattctaaat gtggcacaat aagttttaaa gctttttcaa catcatgcac aacatctatt 2340 ataccttctg cataggcttc tacaaggata tcttttacat tttgtgattt acctttttgt 2400 ggtatcacta gacgcatatc aaactcattt gcttgaggat ggttcttacc ttgccaataa 2460 ccatctttgt taaagctgat gtagtcaccg tggtaaaaat gtacaccatt agctttaaac 2520 ttctccagca caaggcattg aattgggtat tcagtattcc actccctgac tcctataacc 2580 ttcactgttg cgatgtactc ctgtgttttt gcatctatga tgtcaagttc ttgaccagct 2640 atgatttgca tattcgctac cttctaagtt ctacaaaggg gctatcaagt aacccctcaa 2700 gttattactc agacttttca gtcttcttgt cggatttctt actagtcttc ttctcagctt 2760 tctgctcagg ctccttctca gaagttgcct tgataaccat atcaagaagc tctgataagt 2820 cactcttcag taaagtaaca ggctgctcgt tgtagaagtt tttgtcaaga taaactttga 2880 actcttctat agaaggaaat ccaaaaattg gtacaggtgt cttaatcatt acttagtctc 2940 tccataggca tcttttaaga ttgccttgtt aatcatttca gcgattgcaa aacgaacaca 3000 tacagctata attgtaggtt gcattcttta cttacctctt caagtttaac ctcagaatcc 3060 ttaagtcgtt tcttatgaac tctgaacctt attagtgaga tgatgataac agctaaagga 3120 acagcataca agtaccaaac agcatatacc tttgcagtaa tctgtgtaat ggtcaagtct 3180 tgagctatac aactgattgc tgatactgcc agtaacattg ctaagaagaa cgccagtacc 3240 ataacaatac ttaggcatcc tctagcatgg tgttcatgct taatgcactt attcttttcg 3300 tcaacaaccc tgttgtagtc atttgtaaag tctctgtaga aagctttcaa gtattcttga 3360 gtgtagcctt caaagcaacc tgtaccatac caataatcac caccaaaatg tgctatgata 3420 ccagtatctc catttggttt agttactctc aaagatgtgt gatgacgagt atcttgatag 3480 tctattttgt atctttcttc gtaaatcatt tcccaacccc tctcaatcgc ttgttccatt 3540 caaggtcaat aaacctttgc aggactttcc ctctaggtgt tacacctttt aaatctgcat 3600 cgtaacaatg gtaaaagtca ccttcagcgt gtttaccata gcattttctg atattctggc 3660 ttctgcgata ctgttctaac aaggacagtt tgtagtaatc ttcaactgta gttagttttt 3720 tcattctttc accgtagtgt ttctccagaa actaaaaagg gaactacctc tcgatagctc 3780 ccatcataat caatattgta tactcggtca agagtatttt ttaggcagta atgcgctacg 3840 cttgttactc tcttcactca atagtgcgat aaattcatca cctttccctt tccacggact 3900 gaatgtaggg atgtgctctc tgatagcctc aatcactgtt ttcagggcat tgttctttaa 3960 ccaccaatca gacactgccg aagctacgat gtagtaagca ccgtcatctg tgaagattgg 4020 ctcagagata catggtgaaa tcatagtggt gatgatagag ccattattca tgtaatatgt 4080 tcttttttca accttatcaa gaagcttgtg aaggtctgca aagagactta ccacctcttt 4140 atggtcaata tctttttcaa gatttgctct atactttaat agtgcagcat caacctcttt 4200 atcattaaat ttgaagtact ggacttcttc attcacacat acactgatgt tgttggtgtt 4260 tatcgtcaat ttgcacagtt tgactggaga gttaatgttg gtctgaaaaa gtgctacaca 4320 gccttctaca tttccgaaat gcttgactaa tgtaacttct ggttggatat gctcatgttc 4380 ttctgacatt acagtttcct cattaaatac tttttaagtt gtgtgttagg tttctcaaaa 4440 acttctatag aagatatctt aacagactca ccacgcatac cagtatgttt gaatatgtag 4500 tactctaaca tccctatgga ctttgctggt aagtcatgct tgacatacac cgttacagaa 4560 tcttcaaatt caacaacttt tgtaccatct ttgtagttga actctttagg atggttgtaa 4620 ttgtctatgt catacattaa aaagagtctt ttccgttgca tatcaagctt gtttgttaaa 4680 gactctttga tatctgagaa gtttttgtaa actgtgacat ggagcttact catcgttaaa 4740 ctctctgacg aagaaatagt tgactttgtt attacctacc ataaggtcaa agcaggtatt 4800 ttcaaaaggt ttgttgtagg catcgtatga aatatatggg tcagctactt gcttagtgct 4860 taacttctta cttgatgggt ttaagaggcc accatacagc ttcttgatag cctcttctac 4920 aacagaccag ataatttcgt cagtaatttc ttcgtacagg tcaagttcac gctctagtga 4980 gaagtcacaa atagggaaaa taacctgtac tttactcatt aacgaataac ctgtgtgact 5040 tgaattgctt cagttactga taagtcacct actttctctt ctttgataaa ggtgaaggtg 5100 agttcaacag gttcttgctc ttcttgctca actggaatgc cattaagctc atcaaagatt 5160 gattgagttg tccagtcttc tccaccatct ggatagtgga ttgcataaag aggaaattcc 5220 acgtcatacc agccaaatac agggcaaccg tctacatcat cacgtactcg tcgaagagtg 5280 ttgcctgatt ctgtaaatcg aaggctgaga ttaccattac actcaaaaat tactgcatca 5340 gcaggcccaa cattttctcg accatcatga ccaaatgtgt caacctttac ttgaatctcg 5400 ttattcataa aaacctctct ctgcttgttc gatttttgct cttaaatttt cgcaatgctg 5460 tagatggtag ttagcttctt gttcatgtgt tgctaactgc ctttccagaa cagttttata 5520 gtaacctgca agttgctctt ttgtcaatgg gtgctctgaa ataatatcaa gtccactttc 5580 gccaagaggg ttgaattgtc catgctcatt gacatggtaa gtttcaaact tgaacagacc 5640 gttgttagca gattcaatag gtgagagttc agccaactca acagtgaaca ttgtgtgtac 5700 cctatcacca actgtaacaa tgttactacc aatgattctc accattgagc cattgcgagt 5760 gtacttaaaa gttccaaagt cactagccca aagtttcata gttttctcct tagaaaataa 5820 aaaggctccc gaaggagcct atgaagatat tactttgggt atacactgtc aagataaatg 5880 tcagcttcca ttctacgtct gtttttcagg ccgtttgaag tgaccttctt acctttgact 5940 gtaaccttgt tccaccattg catagcttct gcacaaccta ccttattacc atcattgtgg 6000 cgcttgataa atgtagaatc ctgcatagct gtgataccga tgttgtatgt ttcacttaca 6060 agtgcatcga actcgttctg agtagttgga gccttgatag ctttattcac tgctgcaacg 6120 aatttctcaa catctgcgag aagatactgt tcagcttgtt cagccgtgat tttcataccc 6180 atcttaacag gttttccgtc aatacggatt gtaccatacc cgattgttgg gattccggca 6240 gaatctttgt aagcctctaa cttcagacct tcaaagaact taatggcttc taagcctttt 6300 cttgagagtt gcattatgcc tcccctgctg ggttaactgt aactgttgct gcattagatg 6360 tcacagagcc acctgcacca gtaactacac aggtgtagct tcctgaatca gcagttgttg 6420 caccttcttt ggtgtaagtt gcagtagttg catcgaggat gtcttcctca cctttcttcc 6480 attggtaacc tgtcgcacct gttgccacaa cattcagtgt taaggtctca ccttcagtga 6540 tttcttgatt ggctggttgc tgagtaattg ctggtggctt aatagcatct ttcaacttag 6600 cattcagcat tgagaacggc ttaactcttg ccagccattc acagtaaatt gtgtcaacat 6660 ctttaccatt gataattgca tattgtaagt ccatgaagaa gtcagaagtt ctcatttgag 6720 caccaatgct gtaaagcagc tcatcactaa atggaacttt atagtctggt ttgtagtcaa 6780 acttcttaac ttctgcaatg tcagcttcag gccaatacga actataggtg agtggtaaaa 6840 tagactcttg atatgttcta aaatcatatc tcttaccagt ctttacattt gcaatgaagc 6900 ccttcacaaa ctctttgaag tctgggtaag tctttgcttt aatcatttct ttttagcctc 6960 taaatgtgcg tttagtctaa aataaccttt gtggtgtgga gatacatcac caacaacaac 7020 acctttaacc ttataacctt taccaattac atactggata tccataagga atctaccaag 7080 accaacaata tggaacattg gatataatag attctcagag tctggaatat tgatttcagg 7140 tttgtaggtg cgttgttcga ttgttggtgt aatatcttct tcaggccatt tactgagtct 7200 ccatgtcaaa ggtgttggga taacatcatt aaggttgtat ctttcaccat tttgcacgga 7260 attgatatag gattgtagga agcaataaaa gtcttttgca ctcttagctt tcattaaata 7320 tccttataaa tagttaaagg ggcatcagcc cctattcaca cttaagcttt ggtcttaagt 7380 aggttcttaa gttttttaag attcatactc tcatcaaact taaaaccaaa tacattgaca 7440 taatcaatga actcggattt cttactgagt gacaatgcgt aattcatatc aaagttctta 7500 cttgtttctg cgtctggact agagttcaca tcaaatgaga tttctgtagg ctcttgctta 7560 ctttttctca tattatcagt caacaaacat gtatagtttg ctggatagaa gtttacacta 7620 ccatcaacgt agctgtactt attattatgg ataaggttgg aaaatacctt aaggaatgtt 7680 tctgagtcgt ggcaaacaag tttgaattgg ctgctctctc caagtgcaac taatgagtac 7740 ggactttcac tatcgaagtc atagtttgga ttcgatgtcg tcactgttac acgcatcaag 7800 ttattagcaa tagtcttctg tttaaaagaa tttggaacat agtgaagacc tctaccacac 7860 tgattgacta gctctttaag taggtcattt gcatacggtg aattaattga tacagagcca 7920 tcactattgt aattaaaact tactgttaac atttttcagt tctcctgcga tttataattt 7980 tgctgcaata gagaaacgaa gtaaactcac tggaagaaac cattaagtgt tgttcactag 8040 attgagccat tgccctgaaa tacattccag tcaaagcatc atagtgacta ttctttccaa 8100 ttgaggttat atagccatga ctctttgcag tttgatataa atctataata tctgcgattt 8160 ctaattggga actacacata gataatcctc ttgtcttctg taattttgaa agaacaggta 8220 cagaccaatt tcagaggatg aatagtagat taactctacc ctttttgatt ccttacagtg 8280 attggtattc ttacctttct taggtttatt tgattttctc attaagtctc ctttgtagaa 8340 caaggcagac ctacagcttt aagtaagatg gtacagtaat ccatacaaca agtcaagaac 8400 tattgcaagt taaaaaagtt gttgacaagg tacttgacaa ggtgtaggct tataaatact 8460 tagaagataa cttaaaaggt tcctctaaaa aggctattta aacagatatc tttctggata 8520 tctatctttt atcttaaaag ccttttaaga ggtcttataa gaggcatacc aatgaaaaac 8580 agaacaaaca aaggccagtt taaaaaaggc cagtctggaa acccatctgg gagaccaaaa 8640 ggctctcgta acaaaagctc actcgtaaaa gctcaactga ccattgataa ttctgctgag 8700 tttgctgcaa agctgtttga ggcgattgtt acaagggacg ctgctaagct tgcagagttc 8760 ggtttgacga ctgccgatgt aaacctgaag tcgatgatgg aagctggtaa aactatcatg 8820 acccactcag caggtgagat gaaagcgatt gcagcagaca ctaagaagac ccctgataat 8880 ggtggtcagt cacagacaga taacaaacca acgttctctg ctgtagcgac tctcaaaaaa 8940 taattttaaa aggtgttgac agactctaca gagttgctct aaagtctgtc acatcaaaca 9000 acaaatgaga gaagagagta aaatatgagc gaattattta aacatgcgca ccttcatgca 9060 ggtcgaactg aaaatggtgc tgtaaaccat acttcatcaa tgtctgctct tgtggacttt 9120 tacaaagctg ctggttccag ccgtagcaat gtagaaatct taccagacct gttctacaaa 9180 gctttgcgtg aggatgttga tgttgcagtt cgtattttac tgcatatgcg agatgtacga 9240 gaaggtatgg gtgagcgtaa agctttccga actgttttac ttcaagcgat tgaagataaa 9300 gttttagagc ctacacaggt tcttcgcatt atggataaga ttgcagaact tggtcgtttt 9360 gatgacttca aaatcttcgt aggtactcgt tttgagacag atgccttcaa acatttagaa 9420 gcagcattac tagaccctgc aacagcaggt ttagcggcta agtggttacc acgagtaaaa 9480 ccacgccaca aacagtttgt aaaacgtttc tgtaagtttg caaacttaag tgagaaggag 9540 tatcgcacac tgttatctgc actgtctgat acggttgagc aaaaaatctc tgctaatgag 9600 tttggtaaga ttgactacag caagattcct tcactcgctg ctgcacgtta ccaaaagctc 9660 tttaaccgta aagatgggga acgttacaaa gcttacatcg agtccctctc aaaaggtgag 9720 gttaagatta acgctggtgc tgtttaccca tacgatgtga ttaaatctat caagtatggt 9780 aatgcagatg ttgctaatga gcagtggaaa gcactaccaa actggatggc agaaggtgag 9840 aacatcttgt gtatgactga tgtttcaagc tcaatgtctt gggtgaatct tggttcaatc 9900 actgcccttg atattggtgt atcacttgct ttgtatgtag cagaacgcaa cactggttgc 9960 tttaagaatg agttaatggt ttactcaaca aaccctcact tcatcgaact gagtggtgat 10020 ttacgaaacc gtcatcgtca ggtaatgcgt catgttgaat atggttcaac taacttacaa 10080 gcagcttttg accgtattct tgaggtaggt aagcgaaaca acttgactca gaaagatatg 10140 ccaagtaagc ttattatctt ctctgatatg gagttcactc aggttgatgg agctaacggt 10200 cgtacaaact ttgaagcaat tcagagtaag tacaaaaaag ctggatacga aatgccacaa 10260 ctagtattct ggtacttagc aaaccgtaat ggtacttgcg aagtatctgt taaggataat 10320 ggtgtagcga tggtatcagg gttctctcca gccactttaa aagctctgct tggtggtgag 10380 aagtttgacc caatcagcgt aatgctcaaa gcagtaatga ttgaccgtta catctggtaa 10440 aaagttttaa aaagggtatt gacaatgtgt ttgataccct ttaatatgtt ctacatagaa 10500 acgaaatgag agcttttcta agatactgaa aaatatttta aaaaagttct tgacaaccac 10560 taaaaaataa tgttaaagtg gttacataga gtttgaaaag tttatctctg tttagctcag 10620 cttggtagag cgttccgttt ggggcggtaa ggccggaggt tcaagtcctc caacagagac 10680 caaattaatg ttccagtaga caaaatggta aagtcaccac tctttcaaag tggatatttg 10740 agggttcaaa tcccttctgg aacgccagtt ttgacagaag accaattgca gcaaacttaa 10800 tcttattcat ctgacacgaa atcggacaaa gaagagattt ggtctggtca ttaagaattg 10860 cgggtataga gaaagggcgt ctcacatgtc tcattagcat ggtatcggca ggttcgactc 10920 ctgcacccgc ctccaaattt acagaagacc gtttacagca atatttatta aatttttagc 10980 ggaaaaattg aaagatacgg tctggtaata ctaaacatgg ttaggaagca cataaggtat 11040 gtgcggtcgc ctgttaagcg aatggcacag ggttcgaatc cctgactaac cgccaaattt 11100 aaatgtgtcg ttatcccgta gatggtagcg gtggggactg taaatccctt gtcattgaga 11160 ctcggtaggt tcgactccta cacggcacac caaataaagg ttatgtagtt taatctggtt 11220 aaaatactcc cctgtcacgg gagatgatga gggttcaaat cccttcgtaa ccgccaaatt 11280 ataataagta tttcaaaatg atgtttgaga gggctattta gcccctccct taaagagttc 11340 ttacgagtat tctttaaagg agcagaaggc caaattcagc aagttactta aaatttcaag 11400 ccaatttaat tttgaaaaat ttaaaacttg gtctggctca acaattttac agaagaccgt 11460 ttacagcaaa acttaaacaa tctatttctc cggtaaagaa aaggcgaagg ttcgattcct 11520 tcactcggca gatgtcgagt tggtgtaatg gtagcactta agatgataaa caacggtctg 11580 gtaattatct ttgtaggtga gctattaagc ttacctgtga gtatgcgacc acaaagggtg 11640 aaagggtaaa ttctagattt aaacccaaca aggcacatcg ctacagacct taagcaagtc 11700 tgggtagctt atctacaaag ataatttaat ggaagtgtag cagaatggtg atgcggcaga 11760 cttttaatct gacaggcgat gggttcgaat ccctccactt ctaccaatat ggttcagtcg 11820 cagataaggt aatgcagggg tctcataagc cctatgaatg tgggttcgat tcccatctga 11880 acctccaagc tggtatagtt aagaaggtta taacactccc ctgataaggg aacatcggtg 11940 gttcgattcc acctaccagt accaatttca ataaagttgt tgacattgag atgtgactac 12000 tttatagtaa ctgaaaatga ttcagcatat gtataattca aacaccaata catgagcatt 12060 agacgtaatg caatgtgggg aaatttgttg tacatattct gaatagtttt cgttgcgtag 12120 cgtctatttt gcaaatttaa aataaatgca aacgacaatg tttttctggc agtagcttga 12180 taggctaaac accagtgagg tcttccaatc cctcatcaaa gaatttggcg tactagccca 12240 cggtatgatt aataaggtgg gcaacatttt aaagggtatc ccttattggg cttggcttaa 12300 atgcaatgag taccctttaa aatgttaatt acggggcgta tctcagcggt cttctaaacc 12360 gccgttaacc gagtaagtgg agtatgcggg ttcgagtcct gccgcctcga ccaatttagt 12420 tagcagattg cttagacgac cttatcgggt ctccgtgtaa ggaggtggtc tgtatctcat 12480 gttttccaga acatgtaaat aatctgagaa ggggctttac agtgttgtga aaatacggta 12540 agcttcgaat tacaatatgg gacgatgtta agactctaag gcatgagcaa cggcttccaa 12600 caccgtttca aaggggttca actcctccgt cccatgccaa agtcttatta ggggtaggta 12660 gcggctaatg gtagccaaac tgtcttgaaa acagttgcca ctgtagagat acggtgaggg 12720 ttcgactcct ttacttaccg cctaataaga tttacaccgt ccatgcttgc tcgcattttc 12780 ggtttatcca tcgtgtattg tcgtacacac tgataaagca cctagtaggt gtcacggaga 12840 agagataata tcaagctctc caaaggttct agtcaccgga ttaaacaaga ctatgcaaag 12900 acctatttag gtctttttag agggcttcta aggttattac agcttgttgt ggaaccttgt 12960 tgcttaggtt cttagaagtt ctctaaaaag atttaatggg agattgacgg taattggtaa 13020 acctaccatc cttagaagtt ggtgtttgag ggttcgaatc ccttgtctcc taccaaatta 13080 atgcaggtgt agcaaaatgg ttatgcggct gactcttaat cagtaagacg atgggttcaa 13140 ttccctccac ctgtaccaaa cattggggat gtagtttaca tggttaaaac ataagttttg 13200 caaacttaag tacagggttc aattccctgc ttctccacca attagtgcat ccatagttta 13260 aacgggaaaa ttacagtctt ccaaactgag gttgagggtt cgattccctc tggatgctcc 13320 aaattaatgc tcctatcgta taattggcta ttacggttgc cttgtaagca acttatcagg 13380 gttcgaatcc ttgtgggagc accaattcag aggtcaagtg aaagaccgct ggtgtcaact 13440 gaagaccgta acaaattcca cggagttgag ttagcggcac aacttcagac ctcttccata 13500 ctcgcttagt ttatatggta aaacatcacc cttacaagat gaagaaaaag gttcaagtcc 13560 tttagtgagt accatgttcc agtatcccaa ttggcagagg atgcaagctc aaaccttgta 13620 ctagtgacgg ttcgaatccg tcttggaaca ccaattttgc aggattagtt caaatggata 13680 gagcaacagt ctacgaagct gttaataggg gttcgaatcc cttatcctgc gccaagttaa 13740 agaggctatt tagatgagat atttgaagta tgcttcatgg attttcttag ctttgttaga 13800 accatttgca gcaatcttag cagttatctt agcacctttt gtagttccat tctacagtga 13860 gaagaaagga catctacctt tcgggttcag atggatggaa acttatgaca acccaattga 13920 tggcgatgaa ggtcatgtca aaagatgggc taagattaga aagattggta agcttggtat 13980 ctatatgcag agagtcggtt ggctctggag aaacaaagct tataacttct cttaccatgt 14040 gttaggaaga gatgtaaaag atgttactaa gtggaaaggt aatatcaatg taagttctaa 14100 ccctgaagat aatcagacag gttatctcct aatgtggaac agtaatgctt gggggttatt 14160 cgcttttgta ccatcaatta aaatctttgg taaacaattc tactggagaa tttatgttgg 14220 atggaaactt aaaagtgttg tcccagaaga aagagcattc tcaagggaaa gagttatgtt 14280 ggcattcttt atccatccac taagaaaata aagatttaaa ggggattagt ttacaaggtt 14340 aaaacctcgg tctttgaaat cgaagaagtt ggttcaattc caacatcccc cgccaatgct 14400 ccattactcc aattggcaga gaggccagac ttaaaatctg tgttatgtat cggttcgaat 14460 ccgatatgga gtaccaaatt tagcggtata gcataactgg caatgcagca gtctctgaag 14520 ctgtcttatt aaggttcaaa tccttatgcc gctgccactt ctaaggattc ttacgagagt 14580 ccttaaatgt ggccttatca taaatggtaa tgacccatgc tgtgaacatg gtctatacgg 14640 gttcaaatcc cgtaggtcac cccaatttat agtccaagta gcttatatgg ttaaagcgcg 14700 tgtctgaaaa acatgagaag agggttcaaa tcccactggg ctaccaattt caaaggtgct 14760 taatgaaaga gatgacagaa caaggtaagg agatttttaa tctcttaaaa accggtagag 14820 ggttttctaa tcccttatta ctggtgcagc agttctcggt ggaaccgtag ctgcctctac 14880 atcacttgta agctctatta gctctgtaac agaccctaca ataaaggata aacttgttgc 14940 tgctggactt acaacagttc tgcttaacag ctttacaacg agtctgacaa gcactacatc 15000 aaccactaag acattggcag attacggtca aaagtccatt gatgagtttt catcacgtat 15060 gcaggtagca aaaggatatt ccaatgttat gggtgcagca ggagagcaag tcggttgcac 15120 accatttagt ggtattatgg gtgttgctac agagtacggt caaaaagcta ttgacacaat 15180 taacagtaca ctagatggtg ttaatgatgt attaagtgac ttacaagatg ctattgataa 15240 aggtcttgat actgtttctg atttagctaa tcaagctgtt agtaagatta atgaaggtat 15300 ctcgaagatt acagcttatg cagatgaagt tgtgcagatg attgaagaag aagctgccct 15360 tattgcagag taccttaaaa cgaatatcaa tgggttctta gcaggtatct taccagactg 15420 gtttgatgat gcttgtaaaa ctggtgtaat tgacactatt gcaacaccag aaatgaagaa 15480 cgcattacag aaataatgga agattaaccc taaaaggtaa gggagcagtt tgctaaactg 15540 ccagtagctg agaaatcggt gtaccagttc aagtctggta tcttcctcca atttgaatcc 15600 gtgacagaaa tggctatgta cctgtctgca aaacaggttt ataagggttc gagtcccttc 15660 ggattctcca agttatttta ctctctctca attaaaataa taataatgcc ctgctataag 15720 tattcttcct ttcgctaccg aagagtattt ttagacaggg cttttttaca gagttatact 15780 ttataagaag acttatacag tatgtctctg acgtacattg tggtttctcc ttgacggtct 15840 ctgtaccgtc ttttttaagg agaaacatgg ttaactattt ggagaaaaca taatgagcga 15900 gaccgtttat aaagaacttt atgaagctaa taagaagcta gaatttatgc agaatactat 15960 catggcaatt gcagacagat tatctgtagc aacaggtatt gatattaaag aagcgtctat 16020 ggatgcactt cttgacgctg ttgatgcaaa gttcgaagtt aagaaagaag agactgctac 16080 agactctgaa taattctatt tgcggaggtg cttaatggac ttaaatgctg ttaagcagaa 16140 gcgagtggaa gatgttagga aagtcctagc tggagagttg gggctttctg atgaagtaaa 16200 agaaattatc aaatcattcg gtaaagaccc ctctaaattc cttccaactc aaattctgac 16260 tttattaaga tacacaccag accaagttag acttatcttc aaattgatga ctgataagaa 16320 ctatgtagcc cctcagccgg gttctcaaga ggtcttttta aatactaatg ctgacttggt 16380 tctctatggt ggtgctgcgg gtgctggtaa gactgctgca ttgttgatgg attctttaag 16440 atttattgaa gaccctaact ataatgctgt gtatttccgt cgaaacacga cacagttaca 16500 aggtggttta tggcctgctg caaagaaact atttggtaag tttggtgggg ttcctcacga 16560 gcagaagatg actatcacat tcccttctgg ggccactatc aagtttacct acctagaact 16620 tgaaaagcac gctgaaggtc atcagggtat tgaatactca gctatttact ttgacgaagg 16680 tacgcacttc tctgcttcac agatttcata cctacagact cgtctacgtt ctggggctga 16740 aggtgattca tacatgaaga tttctatgaa cccagacaga gaccatttta tttacgattg 16800 ggtagagcca ttcttagatg aagaaggtta cccagaccct gaaaagtgtg gtcgtattcg 16860 ttggtatgta atgaatgatg gtgttatggt ttctgattgg gagagagaca agattcttga 16920 aatgtttcct cttgagattc ctcaaacata tacattcatc tctggtacga ttgatgataa 16980 cccaattctt gacttcttag aacctaaata tcgtggtaag ttggaaaaca acacccctgt 17040 aaacgttgca agacttcgtt tcggtaactg gaaggctcgt gcagaaggtt caaactattg 17100 gcaaagacaa tggtgtgaaa ttgttgattc acttccagaa gatgtattcg atgtcagagc 17160 atgggactta gcagcaactt taccatctga gattaaccct aatccagact ggacagcagg 17220 tgttaagatg ggtaaatcta aaaaagacgg ttgctattat atcattgatg tagtaagatt 17280 tagagataga ccctctggag tcgaaacaca aattaatttg actgctgaaa gtgacggtaa 17340 gcgaactggt atttttatcc ctcaagaccc aggcgctgct ggtaaatcct acgcaacatc 17400 cctcatcagg aaacttgccg agaaaggtta tcgagcaagg gctaaaccaa caaataaaga 17460 taaagttacc cgatttgcgg ggttttctgc tgcttctgaa gctggacttg taaaagtctt 17520 gagaggtagt tggaacgaag cttacttcca agaacttgaa ggtttttgtg gtgatggtaa 17580 aactaaagat gaccaagtgg atgctaccag tgatgctttc aacagtctta acgaagttaa 17640 attattcaag ccaccatcaa tgggtgctca cacagactta gtgagaggaa acccatatga 17700 ggggcttaga cgttgatagc taggtgagaa gaatggcaga tattacagaa acacaagaaa 17760 gcttaccacc atttagaatg ggtgaagtag gttctttggg tctgaaggtt aagaatggaa 17820 gaatctatga agaacctcgt caggcactaa ggttccctga aagtattaaa actttccaat 17880 taatgatgcg tgaccctgct gtagcagcat ctgtaaatat tattaagatg tttgtcagaa 17940 aagtcaactg gagattcgta cctccaaagg gaaaagagca agaccctaaa atgcttgaaa 18000 gagcagactt ctttaattct ttaatggatg acatggagca tgattgggca gattttatta 18060 actctgtaat gtcattctgc acttatgggt tctgtgttaa cgaaaaggtt tataagaaac 18120 gtcagggtaa aaaaggaaag tatcagtcaa aatttgatga tggtctaatt gggtgggcta 18180 aattaccaat cagaaaccag tcaacacttg ataagtggta ttttgatgaa gactttagaa 18240 aagttactgg tgtcagacaa aatctaagaa atgtttcaca tattgctgga gcaattaatc 18300 ttggagaaag accactaaca agaaaacttc cacgagctaa attcatgctg tttaagtatg 18360 atgatgagta tggtaaccca gaaggtcgtt caccattact taatgcttat gtaccgtgga 18420 agtataaagt acagattgaa gagtacgaag ctgttggtgt ttcaagagac ttggtaggta 18480 tgccaaagat tggtttacca ccagattatc ttgatgaaaa tgcagagcct gaaaagaaag 18540 ctttcgtaca atactgcaaa actgttgtta atgatatgat tgctaatgac agagcaggtt 18600 taatctggcc tagatatatc gacccagata ctaaagagga tatttttgag ttctcattag 18660 tttctagaca gggtgctaaa gcgtatgaca caggttctat cattgacaga tattctaagc 18720 agattatgat ggcatttatg tcagatgttc ttgctatggg tcagtcaaaa tatggttcat 18780 tctctcttgc agattctaag acaagtctat tagcgatgtc agtagatatt ctgctgaagc 18840 aaattaagaa cgtaattaac cgtgatttag ttgcacagac ttatgctctt aatatgtggg 18900 atgacgaaga acatgtacaa atcacatatg atgatatcga aactccagac cttgaagcaa 18960 ttggttctta tattcagaag actgttgcag taggtgcttt ggaagttgac aaagagctat 19020 ctaacaaact tagagagcat attggtctcc ctcctgctga tgagtctcag ccagtatctg 19080 aaaagctttc tccaaatagc caaagccgct caggagatgg ttataagacc gctggagaag 19140 gtactgcaaa gacaccttca gcgaaagacc caagcacagc aaataaggca aataaataat 19200 ggctgaaatt atctctattt caaatgctac acgagtgcat tcgtataggg gtgtccttat 19260 cattactgat aagctatctg tagaggctgg ctcaagggtc agcctttcag gttatgttag 19320 tgatggtgga gtctctgacg ttttcactat ttgcaggtta cttgatgcac caatgagtgg 19380 aaaaccgttt atttcaggaa attgtagtga aattgttaaa attccatttg acagttcatg 19440 ccttttgggt gtaaagttat ataactgcga gaataaacgt atcaatgtta atagcattga 19500 agccgctttc attaccctcg acactgcatt tcaatcccca atgacagtta acaaagaaac 19560 aaacagactt gaatacattt tttcacaaaa tgattacaaa gtacttgtca aaggtaaagt 19620 atatgatatg attgtaaatg tggtagatga atctggtaac cattcaacag tccttaaaca 19680 aaaagtaagg tttaattaat gggaacatta actattgatg gtaagaataa aatcctcgcc 19740 acgctaaccc caacgactat tattttacac aatgtagacc caacggcaga ccctacagca 19800 aataaggtta ctcagccagt ggctatttat ttttctgaac cggataatgg cttaattgcc 19860 tcagaagaca cagttaatat tactgttcca gcttctgcaa cggtctcaca ctatagcttg 19920 tgggatgcta acgataaatg cgtggcaact ggtgctctta gcaaacctca attctttgct 19980 gaagaaggta tctatgttat ctcttcagtc tctgtagatt taaacaaata gggtgagtaa 20040 aaatgagttc gaatatcttc agacttgctg atagattatt caaccaacct ttactagcca 20100 ctgaatcatt agctcactca gcagcaactt atgtgaataa cagattgctg ggtgatgtcc 20160 aagcagcagt aaactttgat aaacccaaag gtgaagcaag aagtctttta aaagtaaaag 20220 atgacattgc tattattcct attatgggtg gtttaaccca tcgtatgaca ttcattgatg 20280 caatgtgtac aggtggatta agctcttatg aaggtttgcg tagaggcttt gacgaagctt 20340 tagcagatga gtcaattaag actatcgttc tgcatattga ttctggtggt ggtgaagctt 20400 caggttgctt tgaattagca cgtcacatta tggcttcaag aggccaaaag aaaattattg 20460 cttatgtaga tgagttcgct tgttccgctg catatgctct tgcatcttct gctgaagaaa 20520 ttattgcatc accagatgca gatgttggtt ctattggtgt aatcatggtt catcaggaat 20580 taactaaggc atttgaaaag aatggcgtaa caattaacgt catcaaagct ggtgagttta 20640 aaggtatggg ttcaccattc caagcactct cagaagaaag caaagaaaga cttcaaaaga 20700 gaattaatga tacctacgca acctttacag gttttgtagc tgaatctcgt aatctctctg 20760 aagaagctgt aaagaatact gaggcgaatg tttattctgc tcaggaagct cttgaacttg 20820 gtttaattaa ctcaatcatg tctcaagatg atttcttaaa ttacttacaa ggttctgaag 20880 aggctcctgt aagtttaaac gttaacaatt caggtgaaga aatgactgaa caagaaaagc 20940 aagaactaga agctttgcgt cttcaggttg ctcaaatgaa agctaaagaa caggaagctg 21000 ctttgtcaga tttgactaat aagatttctg cttctgctga agcttttgga tttgatgcaa 21060 aagaagctgc aacgactatt ttaggtgctg gtcttgataa ccctctgagt gttctgttta 21120 tgaatgctat ggaaggtgct aaccagaaac ttaatgaaac tatcgcatcc catgcttctg 21180 caatggaaga aaaagaatca gaaattacca agctgaaaga aactgctggt gctgttcttg 21240 aacattccaa cgctatggaa gaagtgggta atgacggcga agctgatttg gttgaagaag 21300 aaaaagaacc agctaagaat gcttccgaag acaccgctga acaacgcaaa ctggctctcc 21360 agaatgctct aaaatctctt atcaaataag gaacacaaca atggcatatc aaggttttac 21420 taagttaggt aaaagagaac ctctgaatga tatcattctt tgggaacagg ttaccccaac 21480 aggccactct cgtaaagagt acaccccaca ggcatctaca gaatatcgtg taggtgaagt 21540 tctgaaagca gacggtacta aggttacagc agggcaagaa gctcaggctg actctgtatg 21600 tatcgttaac ttctacgcag actcacaact gtcttatcat ggtcagttga aagttgttgg 21660 tatttaccgc gacgcagaac tgaaagacat gcttactctt gaagcaagcg ttgacgctgc 21720 cgaagtcaag aaagctctgg ctgccaaagg tattgatttc gtaccaactg gcctgtaata 21780 aaaataataa gacattctgg agaattttac aatgttgact aattctgaaa aaagcagatt 21840 tttccttgct gacctgactg gtgaagtcca gtctatccca aatacttatg ggtatatttc 21900 caacttaggt ctgttccgtt cagcaccaat cacccaaact actttcctga tggatttgac 21960 tgattgggat gttagcttgc ttgatgcggt agaccgtgat agccgtaaag cagagactag 22020 cgcacctgag cgtgttcgtc aaatcagctt cccaatgatg tacttcaaag aagttgaaag 22080 catcactcct gatgaaattc agggtgtacg tcagccaggc actgcaaacg aactgactac 22140 tgaagctgta gtacgtgcta agaagctgat gaagattcgt accaagttcg atattactcg 22200 tgagttcctg tttatgcaag ctctgaaggg taaagttgtc gatgctcgtg gtactctgta 22260 cgctgacctg tacaagcagt tcgacgttga gaagaagact gtttacttcg accttgccaa 22320 ccctaatgct gacatcgacg cttctatcga agaactgcgt atgcacatgg aagatgaagc 22380 taagactggc actgtaatca acggtgaaga aattcacgta gtcgttgacc gtgtattctt 22440 cagcaaactg gttaagcacc ctaagattcg tgacgcttat cttgcacagc agactccgct 22500 ggcttggcaa cagattactg gttctctgag aactggtggt actgacggcg ttcaggctca 22560 tatgaacacc ttctactacg gtggtgttaa gtttgtccag tacaacggta agttcaaaga 22620 caagcgtggt aaggttcaca ctctggttgg cattgatggt gtagcagcaa ctgttggtgt 22680 tggtcatgcc ttccctaacg tatctatgct gggtgaagct aacaacatct tcgaagtggc 22740 atatggccca tgtcctaaga tgggttatgc aaatacactt ggtcaggaac tgtacgtatt 22800 tgaatacgaa aaagaccgtg acgaaggtat tgacttcgaa gctcactctt acatgctgcc 22860 atactgcact cgtcctcagt tgctggtaga tgttcgcgct gacgctcaag gtggctaata 22920 aacttaggag ggttatgaat gtgttataca ggcgacccag ccaataaccc tcttgataga 22980 gtaagaatcc tctgcacaga cactaataat gatgaaattc ttattgagca gtctgtgcta 23040 gagtggttct atcaagaatc tggaaaggat gaaaagaaag cagccatcaa agctcttaaa 23100 tatttactct ttcaagtagc caagatggga gatgagaagg ttggtggtgt ttacttacgt 23160 aactcttcca gattcaaatc tctgaaagct gtttatgacg accttgttaa aagctctgtt 23220 tcaggactac cctatgcagg tggtattaac cagtgcgaca ttgatatgcg tcgtcagaat 23280 ccttgctctg tcaagaaata cacagaatat ggtgatgctg ccagatacga aggcagagat 23340 tactgcaacc gtgttaatgg cgtatttatt atcgagcgag atgaataatg gttaaaaggg 23400 ttattcaccc cgctagagca aaattagtcg gggctatgaa gaacttgcaa acggctaatg 23460 ctcaagttgg gtattttcaa gaacaaggtc aacatagctc tggtttttct tatcctgctt 23520 taatgtattt acaagaagtt attggggttc cttcagcttc tggtaaagta tatcgtaggt 23580 tgtttgaaat cactatgatg ctaaacaaac agaccttgtt agagcagact aagaagaatc 23640 tatataagca acttagcagt ctcaacacag acccttcaaa taccttagaa gcatttgcaa 23700 agaatgctca aaaggcaatt aaaagaggtt ttggtaattc tgctatcctc cctcctaacg 23760 caccttccac agtcaagaaa aaaggcttta atgcacctct tgttgagaca ggtgacttaa 23820 gagatagcct tgcttataaa atttctacta agaagggtat taagaaatga gactcttaaa 23880 cagacacagc tttatagtaa agcgtaaagt ctctgaagac ggttattata atgatgatgg 23940 tgattgggta gcttcacaag atattgtaga ggttaactgc aaaggtaata tccagccata 24000 tatcaaaggt tctgtaaaga atggtacaca gattgcttta ccggaaggta ttaggcttac 24060 cgatacaaga atcctgtata ccacatataa acttagaact tcagatgatg tagagtggaa 24120 tgagtctgac attgttatga ttgatggtca tgagtatgaa gtatttatga ctatggattg 24180 gtcacagcaa ttagcccata cgtcccatta tgaatatatc attattagaa gggataaaat 24240 gaatgcagtt agaaacagca gaacttgaaa aaggtctagt tagaacctta gtggatgtta 24300 ttggtcacag actaactcgt gataaaaata atagaccaaa tgtaattaga gcttaccctt 24360 ctgataactc aaatgacaaa ggtttaaaac ctgaccagcc atttattacc gtatattgtc 24420 aagatgctgc aacaccttat ggttgggttc ttgataagtt tgttgaggat gatgtagttt 24480 gctacagaat tgcttttcag attcctgtac taattacggt gaatggtaaa ggtgctcaca 24540 gtattatgct tgagcttaaa caacgattag agatgagttc agtcagggat ttaattcttg 24600 aagaaacagg ggcaacagtc ttagacactg gagctatccc gaatgactat acttatctta 24660 atacagattt cgaaaattct gcgcctcttg ttgtaactct tgtaaaaaat tcagtcctga 24720 aagatgaacg tggaggtatt attgaacgtg tcattgttga tggtgaatta gtttacgaag 24780 aaggacaaga gccaccagaa tatactatcc atctagatgt agactccaaa ggggtaaaat 24840 aaatgtggaa tccaattgtt aatgtagata ttacattgaa caccgcagga actacaagag 24900 aaggttttgg gctaccacta tttttagctt caacagataa ctttgaagaa agagtccgtg 24960 gttacacttc cttaactgaa gttgctgaag atttcgatga aaactctgct gcatataagg 25020 ctgctaaaca actttggagt cagactccta aagtaaccca gctttatatt ggtagacgtg 25080 ctatgcagta cactgtatca attcctgact ctgttactga aagtaccgat tattctttga 25140 ctgtagctgt gagcggtgga atctctcagc cattccagta tacttcaaag acatcagata 25200 ctgctgagaa ggtgttacaa cagcttaaaa cacagattga agctgaccca acaattaaag 25260 ataaggtcac tgtgaatgta actggtgctg gcggttcagc cacaatggta atcaccaaag 25320 ctggtgtgaa cgacttcgtg aaggttactt ctacagcaca aacagtgtca attgcaagta 25380 caactgctga cacagcatct actgctttgg cagctattga agcttattca actgactggt 25440 atttcattgc agcagaagac agaactcaac agtttgtctt agcaatggct tctgagattc 25500 aagctcgtaa gaagattttc tttacagcta actctgatgt aacagcactg caaggtacag 25560 aattagctag tgcaaatgat gttccagcac agcttgctaa gagtcagtac actcgtaccg 25620 tttgcttgtg gcatcacacg gcagcagaag actatccaga aatggcatac attgcttatg 25680 gtgctccata tgatgcaggt tcgattgctt ggggcaatgc acagctaact ggtgtagctg 25740 cttctctaca gccagctaat aagagacctc tgacaagtat tcagaagtca gctttagatg 25800 cacgtcactg taactttatt gaccttgatg gtggtgttcc agtggttcgt agagggatta 25860 cttctggtgg ggaatggatt gatatcatcc gtggtgttga ctggttagaa tcagacctga 25920 aaacttctct gagagacttg ctaattaacc agaagggtgg taagattact tatgatgata 25980 ctggtattac ccgtattcgt caagtcattg aaacctctct gcaaagagca gtcaacagaa 26040 acttcctgtc atcttacaca gttaatgttc ctaaagcctc tcaagttgct ttagcagaca 26100 agaaagctcg tatcctgaaa gatgttacct tctcaggtat cttagcaggg gctatcttgg 26160 atgttgactt gaaaggtaca gtggcttacg aataatagag gtaaattgga atggctatgt 26220 atcagcaata ttcccctaaa gacgttgtat gtagctggaa cggcattgct attgaaggct 26280 ttgctccaga ttcattctta cgtctacaga gaacatcacc acttatcaca ccagttgtag 26340 gtgcgggtgg tcaagttgct ctgacaagaa atgcagacaa gacaggtact attgagattg 26400 agctaatgca gacttctctc tctaatcaga tgctttctgc aattcaagct aaacaagaca 26460 atatggaact tgaagaagat atctcttcta acttcgtaat ctacgaccca tcaggctctg 26520 ttctggcaac tggtattaat gcttggttgc aggaattacc gcaggttgaa cttggtcgtg 26580 accagaactc taaaacttgg atttttggtt gtgagaagct agactacact tctacaattc 26640 cagcgtcaag tgtttaataa atcctataag ggggagactt taaaaggtct tccccttttt 26700 tgtttctttt aaaagtatta aggaatcaca atgaaaacag aatctagagt aattaatggt 26760 aagaaagtaa atatcattct gcttggggca agagatggta ttaagatgtc tatgaagttg 26820 ggtaaaattg ttgttccaac ctttgcacag atgctatcaa gtctgactga taaagataag 26880 aaagaagctc caatggttcc atttaaagaa cttgttgaag cttgttttga cagaattgaa 26940 gaaattaacc ttgaagaaat ggctaacttg ttatttcaag gggcaactgt tgatgacttc 27000 ccacttaata ttgatacgta cttccaagca aactacggtg agtttattga ttacttagca 27060 tttgcgctgg aggcaaactt cggaagtttt ttcgaagcaa gcattttcaa aagcctaact 27120 tctcagtaaa catgggtaac actctacaga caccactaac tgatgctgct gtagaggcaa 27180 cctatgaaga agcagacgag atgaaatttg tgcttgctat ttatggtatg gaagggtgta 27240 aagaaacact tgaccaactc tttgctatga cattctctga tttattatca ttgagacaat 27300 ttcttgaaat tcagaggtcg tataaagagg aaattgctta caacgaactt agaagagcag 27360 gaaaaatgta atggcacaat atacagttga tagcttcatt gtggaacttg gtttcagtga 27420 aaaggtaatt aaaggcttgc aaagagttga gaagatgtct atgcaagccg ctcagcgtat 27480 tgagcgaaat atgaataaag cctttgatgt gaagcctaat aaaagttctc aggaagcact 27540 taatagaatt gtaaaaaatg ctcagtctgc ttcgggcaga atcaataaag cactcaacag 27600 ttccttgaac cttgattcac aaggtgtgaa atctcttaag aaacttgaaa ctcaagcaaa 27660 aaagactgca aagggtatta acaagtcctt aagagatgct atgaaggttg acggtaaaat 27720 cactattaag acaggtagag ggagaggtgg acgaaatatc cctcctgttg gtggtggagc 27780 acccagaggt ccgagagtag atgttgctca gagacaaatg gaaagaatgt ttaacaacaa 27840 cttctattca gggttaactc gtagactgga aacaattggt ggtcaaggta accagatggc 27900 agcttctttc agaggaagct tacaaagtat ctataataaa tacaagggta ctggtaaggt 27960 tggtgagtat gagatggaag ttaaaaagct catcgacgta accaaacgtt gggttattgc 28020 agaaaatgct agactaaaat cagttaaaga agcagcttgg ctacaggaca gagctaactc 28080 atcactacgt caattagttg gtggatttgt ttcagcttat gctttactgg aactatcaca 28140 aaagactatt gaggcgggtg taaaaagaca atctgcacaa ttagcctcta cagctatctt 28200 tggagcagat acccagcaag ccagaatgtt tgctgcatca ttcgcacacc agattggtca 28260 gaactataca gataccatga agcagtactc aaactttgct gctggtgctc aaccaacgct 28320 aggttttcaa ggtactcaag agttctataa gaacgctgca atgtttgccc gtatcagagg 28380 tgctaccgat gaagacttga aaggtatcat ggttgcattc cagcagatgg catcaaaagg 28440 taaagttcag gctgaagagc ttcgtggaca gttaggtgac cgtttagcag gtgctgtgca 28500 gctattcgct gatgccattg ggaagactcc acaagaactt gataagatga tgcaagacgg 28560 taaacttctt gctcaagacg ttctgcctaa agtgtctgaa agaatggctg agcttgtcaa 28620 acaagcaggt ggtatgaacg ccgtatctaa gcagactgct acgtcaatgg gtcaagctaa 28680 ggcaatgtgg gataacacac ttgtagcact gtttaacaat tctagtgagg gtatttcaca 28740 gttatctaac tctgttgcaa tgttcttaca aggttctatg gggtctacag aagctttagg 28800 tgttgtgatt ggtaacctgt taaaaggtgc tagtaaccta cttgactttg ttacagactt 28860 catgtacaga gtctctgcac tatactacta tgcaagagct tggtataaag accttgacag 28920 tagtcagcaa aaactagtca aaagtgctgg tgaatttctg ggaacagtca ctatgattgg 28980 tggtgctgta gcaacggtag ctaaaatggc aaagcttatc actggattct ttgatacagc 29040 aattgtgaga aaaatccttc agaggcttgg tattgaggtt gcagaaaaag cagcaccacg 29100 agcagcacca ttacttgcat ctccagttgg tgttgcagca gcaacgcttg cgctatctaa 29160 gtcttctgac cctaatgctg gaaagagatt caatgaagct aatatcacta atcctttcaa 29220 tgaagctgtt gcaaatatta caaacccaaa aagaccaatg ttctttgatg agaatggtca 29280 acttaagttt gcacagtaca ctcaagatat ggaaggtaac agaaagctaa ttgacaatgg 29340 tctatctaat tgggatattc tcatggagaa gttatcagca tctcttgata attttgccaa 29400 taagtttaat cagacaccaa tgatgatgac accttctggt ttacctatgc agactaaaca 29460 aaccctgaat gttactttca aacttgatgg taaacaaatt gctactaaga tggtggatat 29520 tactgacaag aatcaagaag acattcttct aagttcaagc tatccagagg aagaataatg 29580 ttatgggatt ctaatatgca aatcaaatat agtggcaaag atggcatcta tttccactta 29640 agagataatg tagatgcctt cttaacctta tcagcaactg aaaacatgga atttgacagc 29700 cctatgcagg taactacaca gaacatgcaa tcagggcaaa ccgtcacaga taatgttcaa 29760 agagcaccca gaacaatcac tattagtggt gtcgttgtag ttggctatga aggaagctta 29820 ttattaactc gtcagggtca attagtagaa aacttcatcg acactctgga aaactggcgt 29880 gaccagaagc agattatttc ggttatctgt aaagacggaa tcaagattga tgattccatt 29940 attacgagct ttaaagcctc taaagatgtt ggtatttcaa atggtctaag aatccaacta 30000 acctttcagg aaattaactt caaagctgtt gtggggcaaa ctgatatctc tgctgcaact 30060 ggaaaggccg ctactacgaa tgatggtggt gcaacttcta agaagaatac tggcaacact 30120 acgacaagtt taggcaatgg taaattaaac tgccagttat tatttgacct aaacgccaat 30180 ggtgtaaggg aacttactag tgctgaagat aaggctcttg gaaaatgttc aatgtctgca 30240 aagacaagaa aaggtgttac cacatttagt gacgaggctg aaaaaaatgc cggagcagcg 30300 ttaaatagga ctgctggaac tggaaaggca ttacaaaagc actcagtgaa tccgaataag 30360 aaggagactt attaatgtca caatatattc ctgttcctga tacagaatgg tctacacaaa 30420 ctgtaactct ggatggcact gtctttgtaa ttgagctaaa gtataaagaa aggcttgaca 30480 gatggttctt gacgctatct gatgttgatg gtaatgtatt attacatgaa aagaaatgcc 30540 ttgcagacca atcaatcaca ggacgctatg taattccttc attagctgga gagctttttg 30600 ttgaacgaat gtacggtact gatttacaac ctaccagaaa taacttcgga agagaaaagg 30660 catttgagct taattattac actcaagaag atatgagatt aatggagaac ttataatgtc 30720 tgtaaaagat agcactgctg gggcttcttt taggtgctat caattggctg taggtagtga 30780 aactacagcc tttaatgata aacctacaag ccatgctaaa gattctatgc aaatggacta 30840 tttcgacaac ttacaattca cttgtaatgt gtcttatacg tctcagaaaa ataaagtaac 30900 ctctgacgat accacttttg aaatctacaa ccttaataaa gagatgagag ccaaattcaa 30960 aaccgttggt gcaacagtta tgctcagagc aggttatacc actggtttta aaagggactc 31020 aaacggtgac cttattattg aatatgacaa cctcccatta atttatctag gcactattga 31080 gtatgcttat acctataagc gtggtgttga tatgattacg aaggttatct gttccaatga 31140 taaaatggaa agaaccacga ttaagacatc aatttcttat aaagcaggga caacacgtaa 31200 aagtgtgatt agagatttag ttagcagatt aggcttctca cttattgatg aagacctttc 31260 aagtattgat ggttacactt acaagaatgg ttttagtgtt tgggggagtg ttgcagaggc 31320 acttacaaag gtttgtgaag aaagtagtct acgttggtat acatttaaca agcaaatccg 31380 agtagtccct tttaatgcta aagctagaca actttcttgg gaaatttacc catataacgt 31440 tattgactct ttgcaaggtt actacagaag aactagaaag gttctgaaaa aagagaataa 31500 gacagttatt aaagttaaga ctggagttcg ttgcaaaatc catttagatg ggagaattaa 31560 gatgggtgat aacatcacta tcagagaaag tgaagatttt gaaggtcagt atcgagtaaa 31620 aggtctttct cataatcttg actttactgg tggtgcttgg acaactgaac tagatttaga 31680 gaaggtggaa taatgaagtc accagttact agaatgtctg ggtatgtttc agaatgtctt 31740 gatgaattta gaaaagaact gtatactgga ttaccagcta ttatccagtc ttttgattca 31800 aagactcaaa cagccactgt taagccactt tactctatta acggtttgcc tatgccagag 31860 attactggtg tacctgttca attcccaagt ggtggtggag catctttaac attccccgta 31920 aaaactaatg acagatgctg gttagctttc tcaatgttac ctttagatga cttcgttgtc 31980 aatgacaaga atgttcagat ggaaacaaac atgagaagga cgcacgatat ttcagactgt 32040 gtagctttcg taggcatctg cacaagaaca cagaatttta aaccagaccc aacagcagtc 32100 agactccatt ttggtgactc tgtattaaga atcactgatg atggtaattt ctactttgaa 32160 ggtgatgtac acatttctaa aaacttatat gtaacagaag aagtacatgg ttcagatttt 32220 atcagtgaca cgactggtgt gagctttaat gaacacacgc accattatta ctggacagac 32280 cctgctggtg aggctgatac tacagaggca caataatgaa aacagacttt gcattaaatc 32340 taggtggtga ctatgttgcc actttaggtt cagattcagt gtatgtggct catggtgatt 32400 taaagattac tggtaaccaa attagaatta tcccagagga tgataaagct actcaggttg 32460 ctcaaagact tcatattaga tgccttctaa gggctggtga agtcttcttt aatacatctg 32520 ctgggttccc atatttacaa cttgccaaat ttaaacagaa aacttctatc tttgataatt 32580 atatgaaagc ctaccttgtt gaaacaagag atgtatctaa catctataac tattcttctt 32640 caatggacaa tgctcaaaga aaagtgactg ttaattttga tgcaaccact acaacagata 32700 ttttaacaga cattacgcaa gaggttaata tctaatggca ggactaacta caacaggatt 32760 acaaactcta agatatcagg agatttttga taatatcaaa tcaagacttc ttagagatat 32820 ttcaccaaac cttgacgttt ctgaagacag tcaattagga ctcttcctag cttcaattgc 32880 aaggtcttta gcagatactc atgagattct atcagaagtc tatgacggtg gaacaattga 32940 caaggccgag ggttttaacc ttgacgatat tacagctttg aacgctgtct acagatatgt 33000 tgctcaggca acaagaggtc aagttgagtt tactgggact actggtgcta ccattccttc 33060 aacaacaaga ttaagaagta ctgccggaaa catcttttat ccagttaata acatcaccct 33120 tactccatca tattgtgttg aagctacact tgaagttaac tctttacgaa ctgatgcaga 33180 ttatgttatt attattgata acgtcatttt ctcatataaa ccaacctcat tagacacaat 33240 caccacgctg ctaacaaaat tagcagaagc tattaatggt ggtattgtag caaaagcaga 33300 agtcattaat gatggagccg cattaagagt ctataaagac gaaggtgata tcattgcaag 33360 aacaaaccct atggttgtca ctgcaacaac gtttctgacc tttacaaaga ttacaactat 33420 ttcagatgta gtagctgaag aggtgggtgc tacccctgct ttggctggta cgcttattga 33480 gattgagaca actgttgatg gtcttgacag tatttataac agatatgact taacaactgg 33540 tagaaacgaa gaaactgaca cagaacttag acagagatat ttagagtcct tagcagttac 33600 tggtgtgggt actttggatg caattgtagc tgctgttaaa agagttcaag gtgtctcaga 33660 tgcttcaggt gttgaaaatg atactgaaga gacaaactca gaaggtcttc caccaaaatc 33720 ttttaagatt gtcgtagttg gtggtcaaaa tgataatgtt gctcaggcaa tctgggatac 33780 aaaacctgct ggtattaggg cttatggctc aatttttggt acagcccatg atttaggtgg 33840 tttggcacat aatatttatt ttagcagacc aacaccaaaa tacgcatttg ttaaggtgtc 33900 ttactcacta tacgacgaag aaaacttaac aatccctgaa gaggatatca gagacagcat 33960 tgtacaaggt attaatgcct acggaagaac tcttaaggtt ggtaatgacg ttatccctaa 34020 cagaatctat ggacatatct atgacgtaat taaaggtatt gagattaatg aagttaaagt 34080 ggcattatca aataaccaat cagttccacc tagtgacggg cagtatacta cagcaagaat 34140 tactgttgac ggtgaccaat atactgtttg ggaaagtagc cagtatacca tcactaagga 34200 gtaataatgt ttgaaaagat tgatagtgtt tattataaaa cacttgatga aaggactgta 34260 acacagttta aagataaatt tatctataca agtctcttga aagcaatcac tgatgagcta 34320 caaacactag aggatgtttg ctggcagatg cacacagaga gaaatatcag gacgtcagta 34380 ggtcaacaac ttgataatat tggctcactg attaaagttc ctagaccttt aggtgctgat 34440 gatgaaacat acagagctat gctttatatc caaatcttcc taagacgttc tgatactact 34500 ccaacattct tgcaaaaagc aattatgaca ttgtatggtg caactttctc tcagattttt 34560 gagcatatta ctcctaagac tggtggtatc gttatccgta ttaatactag aaaaagcgtt 34620 cttgatgctg catatacact gtcaaagatt tctgcaacaa ccactggttc cgctgttatc 34680 ttaagagatg ttactttaaa tgggactgct tggacacctg tagaggttgc tgattcatca 34740 cttgctattg ttgatgataa agagaactgg tttgtaactg atgctaacag gggtctggta 34800 acaaataaca ctggtggctc tctggagtcc aacctagtag ggagtcttgc agatgctggt 34860 gttattgatg gttactttaa ggttgacaga acagcaaacc cacagagcga tgattatatg 34920 actgtagata ggtccaataa tagtggctat ttcattgctg gtaaagaagc tattgcaggt 34980 ggtgcatatg gaatcatggc tgaggttgca caaattgtca aaggcagaaa agataaatca 35040 caacaagaag gaaattctta atggcagttc taaattggtc tacaaacgaa gtagatactg 35100 atggtaatca gttaaaagtt ttaccaccac cggaagttca agagacaggt cttttaaagg 35160 gtgagcctat gggtagacag tggttcaact atattatcaa ctacctgctg aataaagtaa 35220 atggcactgt tggtgaagtt cgttcatatg caactgagca accagattta gtggctaatg 35280 gctggaatct cattaagtct gagacaggga ctgcatcaac aagtacaaga aacctttaca 35340 catatgaata tgtaggagct taataatggc agtaggtgaa attcaaatta gtgccttgcc 35400 acaagcggcc ttaccagttg atttgagtga tatcttccac cttaagcaag gtgttgagga 35460 taaaagatgt acgcttgagc agttgttagc acctcacgca tctttgagga ataaccctca 35520 tggtgtaact aaatcacaag taggtcttga taatgttatt aactctcttc aattagttgc 35580 agctaataac ttgtcagata ttgtaagtgt tgctgaggca agagcaaatc tacaaattat 35640 gtcgtcagag gaagtgaata acttaattca gcaacatatt gacgacaaaa gtaacccaca 35700 caatacaacg aaagcacagg ttggtttaag taatgttcag aactggacaa catctaatct 35760 gtacaatgaa gatgctgata agtatgctac cgcgaaagca gttaataatt tatacaaagc 35820 tatccaagcg tcatatccag tagggactat tcatctatct gttaactctg ctaacccatc 35880 cacttacttg ctttgtggag gtacttggga gttagtttct aaaggtagag cactagttgg 35940 ttatgataca gattctagac ctgttggttc aacgtttggt tctcagactg tagcattaac 36000 aaataataat ttaccagcac atactcactc tatctatcta acaggtggtg gtcatacaca 36060 ctctgcaagt gtatctatct ctagttttga ttatggttca aaaagtacat caacttttga 36120 ttacggtaca aaaacgacta atagtgctgg tgctcacact cacacgttta gtggcacaac 36180 aagtaatgct ggtaaccaca accatagagt ccctatgagg ggtaatgata ggggtggcac 36240 aaacgctatc actgcatctg ctgatgctgg tgttggtaat gctatgtata ctgatttagc 36300 tggtgctcac acccatagct tctcaggtac aactgcatca tctggtgctc atagccatac 36360 tgtcgcaatt ggtgctcaca gccacactgt taatattggt tcgcacagtc atacaggcac 36420 tgttactgtt tctagctctg agcatacaca ctcagggaca tctggttctg ttggtggtgg 36480 tcaagctttc agtgttgagc agccatcttt tgtagtgtat gtgtggcaga gaacagctta 36540 atttctttac aggggctata aagccccttt taagaggaaa attcataatg gcagattaca 36600 aattgagtca attaaactca atcgacacaa ttcgttcaga agacctattg cacatcagag 36660 ttaagaaaag acctgaaatg ttgggtgacg aagaccgtag aatgacctat caagacttct 36720 tagcttcctt caaactagaa aggtttgttc agattgctgg gagtactatg gttggggatt 36780 taggtattgt caagttactt tacggtggta aggcagtatt tgacccaaca ggctcttctg 36840 agattactat tggggatatt ttaaagactt ttaaaattaa ctcaaatggg cttaaactca 36900 ctattgcaga tgccacaagg tcggcaactg tttatcatac tttgaataaa ccaagcccta 36960 atgaacttgg tatgagaact aatgaagaga atgatgcaag atatgcaagg cttgctgtta 37020 caaacacatt ctctggaact cagaacattc aaggtgatgc taacttactt cgtcttagaa 37080 accagaatgc aaataatgcg caatatattg agggtgtgaa cttagatggt tcagctagat 37140 ggtgggttgg tattggtagt aatggctctg atgaagtaaa actgtacaat aacaaataca 37200 actcagcttt gactattgca agcaatatct ctgttaataa gtctttagca atcactggac 37260 aagttcaacc ttcagatttc tctaacttag atgctagata cttcactcag acagttgcta 37320 atcagagatt tgcacagtta gctggcaata atacttttac aggtgctaac acatttagga 37380 ctatgagtgt tatttcaaat gctgctgcta tcacactgca atgtgcatca gcaaacgaat 37440 ccctgtatct acttgcaaaa gattatgaag gtggaaactt atggtatctt ggtaaaggta 37500 gttcaggtgc tggtgtaact atctacaact ataccactga cacctctttg gtcttagatg 37560 ctgctggagt atcagcaaat aaaaatgtca gaatcactgg acaagttcaa ccttcagatt 37620 gggctaacat tgactctaga tatattccgg cagcaacatt aagtacaatt gcaagaacta 37680 atgcaaggaa tacttttaat ggtgtacaga cagttgttac ggataatgaa ggtctgattg 37740 ttaaaaactc tactcagaat agaccattat atattcgtgg tgtggacact actaatgtat 37800 caagatggtg gattggtgtt ggtggtgctg atacgaatga tgttacccta aataacagtt 37860 attctggaac ccaattggtt ctcggaaata caacatcata cattaacaaa acattgacta 37920 ttgctggaca agttcaacct tcagatttct ctaacttaga tgctagatac tttacgcaaa 37980 gtgctagtga tagcagatac ctaagaatca gaagtactag ttttaattta ggaaacggtg 38040 aaaagtgggc taaaatcgct actgttgtaa tgccacaatc aacatctacg gcagtcattg 38100 aggtttttgg aggtgctggt tttaatgcga ataacccata ccaagcaggt aagtgtgaaa 38160 ttgttttacg aacgtcaaat aataatacaa aggatttaaa tgctgtagct tggagaacag 38220 cagataatgc cctcatcacg gatattggtt atattaacac ttctggtgac acttatgata 38280 tttactgtaa ggttggtggc taccaaaatt ctacggtatc tagggttcaa tcttctagta 38340 atgcaagtgt acagttgttt gaagtcccgc aaacatttga tgatgctcca caaggtattg 38400 tgaagggtac acttgcaagg tactacacaa gtttgcaaaa accaacccct tcagatattg 38460 gtgcatacac taaagcagag actgaccaga aaattgcaga agcgattagt gactctacag 38520 acctgaataa aatctatcca gtaggtattg tgacgtggtt taacagcaat gttaacccta 38580 atacagcact tcctgggtta acttggacgt acctgaacaa tggtgttggc agaactatta 38640 gaattgcagc agcaaatggt tcagatgttg ctacaactgg tggttcagat tctgtaacgt 38700 tatctgttgg taacttacct tcacacacgc acagtttctc tgctaccact tcgacgtttg 38760 attatggcac taagcacaca gatggtcagg gtgctcacga ccatgataga ggtaatatgg 38820 aaattcatgg tgattttggt ttcttcagga gtgacacatc aagcttctac actgctagtg 38880 ggtcttttgc tatctcaggt tcacaagcat ctagaggata cacaggtaat aacttcactt 38940 acggtactcc tgttaatttc tatgcctcta gaacttggac aggtagaaca agttgggtag 39000 gtgctcatac acatggtgta ggtattggtg ctcataacca tacggtaagt ggtaacactg 39060 gtggtacagg ttctggttca gcatttagtg ttactaacca gttctacaag ttaatggctt 39120 gggtaagaac tgcttaatcc cttattgact gattgttaag atggtgttaa tattctttat 39180 gggtattctc accatcttgg ctgatgaggt gattaaatgc ctacaatcct agcaattctt 39240 ctaaaaaatc taggtagctt cttctggaaa ctcattttat cccttctaag tgaatacatg 39300 attgagaaag tgttctttag gcttgcaaga taccttgcga gtaaaacaga cacacctatt 39360 gatgatgagt tcgtagataa cttagagaaa gcttttaagg gggagaataa atgaagtggc 39420 tagaggaagc ttttaaaaat aatattggtg caattgtagt tggtattttt agtgttattg 39480 ggatgtatac cacgatgcaa gtttcaagtg gtaaacaaga agtgtctgtc tcaacaaagt 39540 tacagcagct agataattat tcaaaaagta attactcagc tattcgtgat ttacagtctg 39600 acatgagact gctacagcta gggatggaga accagaaagt ccagttagag aatgttaagg 39660 gtgagaacgc aaaacttact aagactcttg ataaattctc tgatagtgtg aacaatctgg 39720 ctcaatcagt atcagccctc caagctatta ctgaaaagaa cacaaagaat actgaaaagt 39780 aaagtttaag gctccttttt acgggagcct tttttgtttt atttacctac tgacaaaggt 39840 gcttcaatct ttcctgcatg ttggtaattg ttaataccac caataaagtc acttgcagtg 39900 agatgtttta agtcacttaa agtgttaagt gggataccaa tctcaaaagt tggtgcatgg 39960 aactcttcat tgttcatcag ttcataaacc tgtttcatat ggttctgata aatctgagta 40020 tctccaaaga cacctatcaa gtaccgtgga gtatatccag tcatcttaca aagaacttcc 40080 agaataaaac cgtaagatgc aatattaaat ggaagtccta aaaaggtgtc tactgaacgc 40140 tgataccatt gtaagtcaac ttcaccctcg ttagtaatat aaatctgaaa cagaacatga 40200 caaggtgcta gagccattga gtttgctgca atatctgccg cattccaagc attaacaagc 40260 atgtaacggt ctgtgatatc acccttcatc ttcgttacta aggtctctaa ctggtctaca 40320 acacaaccgt tatgaccttc aaagtttctc cactgaacac cataaattct tccacccgca 40380 tcttctaacc aatcttgttc agaagagtaa ttagagctta accagcgttt aaaatcatct 40440 gaccagatag tccagcgttc tccatcattc tcaccccaag tacggtaacg gagttcaccc 40500 agcttattct caccattcag gaaccataaa gcttccccga taacttgccg tgtaaacacc 40560 tgtttagatg ttaagagcgg gaaaccagtt cgcatatcaa aacgaaactg aggtggagca 40620 aatgcagaga taacatctcc agttcgtgta gtacgcagtt caccaactga taaaacatgg 40680 ttcaggatat ttttgtaact caaatctgct tgtgacatat caaaagtgtc cttttacttg 40740 tggaacataa atttcaaaag ttgctttacc atcctctgat ggttttgact gtacctttgt 40800 aaatacacgg ttatcataca gcttctcaaa gaagttttca aaaggtaaat gcacagtggc 40860 ctcttcagta actttatgga aaactgtatg aaacactaca tcagcatacg gtaaagcatt 40920 gacaaggaca cctgcaccac caattacaaa gacatcttca tcaatagagc tatcaagata 40980 cttcaaaaat gctccaaatg actctttact ggctttagca tacattacct catctttacc 41040 aaagtctatg cctaagtatg gtacagagtt tgttaagatt aggtttgcac gttctggtaa 41100 aggtttacta cccagagtct taaaagtctc attccccatc actactaagt tatttttagt 41160 gagtctctta aactcttgca tatcctgttt atgtcgaggc cacggcatac cagttggagt 41220 accaaactca ccattttcac cacttgcaaa gattaattta atcattttgt aaaccctttc 41280 ttaatgaacc agttgataac attcttcaca gctttattgc tatggtagat taggtgtggt 41340 gtaggctggt atgaaccata ggcccagaat gatagatgct caccacaacc aacacatgta 41400 gtactttctt cagctatatg accattaaca atcacatgaa cttcaccttg caagtctgta 41460 cacccacaat gtgggcaacg gataggtgtt ccatcagact catagcagtg ttcaattttc 41520 atttatttaa cctcaaaaac tggctcaaga accaatataa agtctacaca atcatcttct 41580 tcatccagaa taccatcaaa gttcttagga acgaagtcga agaggctcat aacaaaacag 41640 tcagaagtaa ccctgatagt tcctcccatg ttctctacag tcaacactgt acgactttct 41700 tttacctctc tcagaagatt actcacaaag tcatctaaga agtacttcat cagtgactta 41760 aaacctttag ggtaatctgt accagagtat gtttcaatct ggggtacaag cttaacattt 41820 atactagtct ttgttaagaa cgtgctagag aacatgctat caggtaactt acaaacaatc 41880 tttccagtac cttcatgctc aatctcaaca aaaccagctt cgtcgccaca tgtaactatt 41940 ttaaaagatg cttcattctc atgctgtgaa gccataaact ttttaagcat cactttaagg 42000 aaatctgcat gagcatcttg taagtagata tcaatcatag ttaatcacct attatgggaa 42060 cagacacttg atgtcatcat ttttgaaaac aaaacttgtg tagttgtgac catcaacatc 42120 cagccaaaca gcctgaacat ctacaccatc aagattgtgg taaagctctt tgatgaagtg 42180 gtctttcaca acctgactac tagttgtttc cagcttaatg tttgagattg ctgaacctac 42240 agccatataa cccatgacac gtttcttctc agtatgctta atcttaccat ctttgtaagc 42300 cataatgaga ttggaaagaa tcttcacacc ataatacttt tcaaggtgag taggtacacc 42360 gtaaaaacct aatgcgaagt tttcagagtg gataatgttt tcacgtttca tattaatctg 42420 ccaaccttaa attaaaatta acaccaaatt tttcacatac ttccaacata aactcaagag 42480 agacattacc agtgaggttg attatgttgg atacacgagc ttgagagata ccacaaatct 42540 tagcaacttg ctcttgagaa agacctctgg atttaatctc tctcttaaaa cgatgtgcaa 42600 cgaagtctct catttcgtct acatccattg gacaaatata actctccatt tcagcttctc 42660 tgtcagcctc ccaatcatct tgtggagcat aagggtcaaa aacctcattc atctttcttc 42720 ttccgtttac gtgaagcatc aatcaatgaa tctatgtttg tagctctaac cttttcacgt 42780 tcatcgttaa gataatcatc aagagccttc tcaatctgtg aatcatcttg acagataact 42840 gtaaagactg taaagccatc tatatcatca attatcttac cataaccgct tctgggatgt 42900 aactttttaa gagccatatc aaatacctgt gcagcttctg ttttctaaga aatactcaac 42960 accatacata gctttttgca tcaagtcttc tttaaactga atacgatgat tgagcatagc 43020 ctgtacatca atatcttcat ggtgcttctc tttaatgttt gcagattgca ggaaatactc 43080 tgcaagaaca cgatactgat agtcagttac cttatcagtc atctctgtta aagactcttc 43140 agagattggt ttaagtaact caccattagc caaagcaaca cctttaacaa tctgacaagt 43200 gtcttctgga acacctgata agtccacatt tgggagttct gttgcattga ctggtaaatt 43260 cattgacata accattgcag cagctaataa aatctttttc ataatgacct caaagttata 43320 ttaaattttg tattacattg agtataaaaa taagctataa cacctgattt gtcaacagat 43380 tttatagctt atttggcaga ttttttttat aaggctactg ccatccttcc ataccaaacc 43440 ataccagaca tagccatacc cgaccgtacc tcgcctcaca acacttaaaa atcctcttag 43500 aagactctta agtgatgtaa tcgaatttta atgtagctcc gattaactac ccatacctca 43560 cctcatccaa ccataccatg ccttaccaga ccgcacctta ccttattaaa agaccctatt 43620 taaagacctt ttaaaaaggt gagtctcatt ttaaatgtag ctgagactaa ctacccatac 43680 tgtaccgcac ctgacccgac ctgaccagac ctaacattac cgtgccacac cgtaccgaac 43740 agaacattgc catacctcgc atcacttaaa aaccctttta aaagactctt aagtgatgct 43800 ggtgagtacc cgtcggttta tgctgctcag tatactcacc aaattttcta tgtcaacaac 43860 ttttattcat aatccctaat aactagtccg acagggaact gtaaagaacc cttacgagtc 43920 atcttctgga actgtaccgt taaaggcttc ccgataaact cttcaggatg ctcagcaaga 43980 tactgtttct tctcatgagt agtcttccat gagacatcta caaagacgtt aggaagagtc 44040 tctacaacga acttgccatg accacgctta tcagtcttta caccagtcac tttaaactct 44100 tcagtgtgca tcttcttgtg cttaatcaag aagtatgaac ggtgacaaca ctcatagaag 44160 gagtcttcag agattgaacg gtacattgca ccttcaaact tagcttcaac ccacttatca 44220 tgagcttcat caaactcttc ccaagaattt acacgacgag acttaacagg aacaacttta 44280 cagccgtctc tgaagtcatt caatggtgaa gtctcaataa tatctctacg ctcaggccac 44340 gtcttagtac tatcacagat atcgtaccag taaaacttga gcaagtgtct gtcaggattg 44400 tcttcatttt taatcatgga gacgatatct tctaagtccc acccatgagc ataaatctct 44460 ccatcaaatt catcaacatc tttgtggagc cttagcattg ccataatgtc aggtattagt 44520 tcggcaggga ttttataaac agtattttca cgagaatatg ctgtaaatac actgccaata 44580 cttaagtgtc ttgaaattct acaacggaca ccatcaagtt ttggttgagc atcagcaggg 44640 aacttcagat actttgcatg actaaccttt gcagcatcat gagcaagctg cacacctacc 44700 ttctcagtat tctgtgcaga ctcttttgtg taagcatagc ctttgcggtc aacctgcttt 44760 ttatacttag cagcaacttc aaagagagct tgctgttcag cgttacgctc attcttttta 44820 ccgatgtttt taggttctgc tgtatactct tcaaacatca tcttgccatt ttctttgcca 44880 tacgtggtaa caactttgtc acctacagcg acacatgacc agacgttaaa agagccatct 44940 ttattttgtt tgtacagtat tgtcatttta ttcctctgag tgataccaag tattgcaagc 45000 attacatgcg taaagctcta agtcattttt atctggttta tgaaaacagt ttgctccgca 45060 gtggcaacga aacggctttc caccaactgt caggatgaag gattgaacct ttccatcagg 45120 agtccgtaca gcatttttat gcttgtcttc tttattcatt tgtgctattg cctttgtcag 45180 atttcatata ggacatgtta ctatgccttt taataaaatg tacaacgcat tttggtgtat 45240 cttttgtgtc tttgatgtgc aatctatcga aactgtgtac tgtgaaggtt gcatctgtca 45300 ttgtctgctt aggtttcatt ttcttttacc accaatctct acgtcaataa cttgaacatc 45360 accagcaaca tcaaacttat gaatgatgct ttccacagtg taagtccaac cctcaatgcg 45420 aaccaactca ccttctcgtg ggacgattgg gttacgttga gctacggttg tagtggagtg 45480 aacaacatca taacagtaga tatagtttac taggacttcc atatcttcac cttaaaagaa 45540 taagtcagat gcttttgggt tgattaaact catgcagttt tgaagcatgg cttcattgta 45600 cccatcttgg caaactacgt agagtttatc gaaagtttct tttgatgctg ggtagactga 45660 taactcctgg catacactaa gataccatta gtaatctaag cctctgctcc aagcgtcagc 45720 gattagggct gtagctttgt ctttgcttct gataacttca tcagactttt caattttact 45780 gttcacgatg ttctacctct ctgtacgttc gtcgatagta tatgataagc tgtgctaact 45840 cgttgctttt aacatctgaa cgtagcagtt gccaatcaaa acctttaccg actcttccat 45900 ataagctaaa taattttact ttgcgtttca ttttggtact cccaatactc agaggccaat 45960 actaatacgt tcacccttga ggactcctgt acggtctctt gcaatcttgc cgtcaacaat 46020 aaggatatgc gcagacctta aagattcact attaaaacct tttacgaact tgctaggcat 46080 cactacaatg tacatcttct gaatcaactc tggagtgtag cagttatcat gaagttgctg 46140 aataacgtct gcaagtgtca tttttgatgt ctccaatatt caatatctac aagttcttgt 46200 gcaatgcttt tcagattacc tttcaagaaa accttctcag aacctgaaag agatgaattg 46260 tcaattaacc tgttcatcct ctcaaacaac ttctgtttac ggttcttgat agtttccttt 46320 gaagcacctt tcatcatcgc tgcatgggtt cttccacggt ggctcataag ccctcctata 46380 taagatattg tataaggtac tcttccctga gcaccttgtc aacttagttt tgcaaactct 46440 ccgtggagtt tcacagcagc ttcacagtaa gctttatggg cttcttcagg tgtgtcatgg 46500 tgacctaaaa acatcttctt acctttataa cttatctgtg cgacccactt accagacttc 46560 ttcttaaggc ttacaccctt gtacccagat ttattggtgg ctagtttacc tttattccaa 46620 gcactttgga agtcatctgc ttcccttaag tttgcaatcc tgttgtcaag agagtctccg 46680 ttgatatggt caatgatacc ttttggcatc ttgccatata cataaagcca tgcgagtctg 46740 tgtgctttat gtgctttctt gtcaaaatag atactaatct gtttatgacc agttgaatca 46800 gtctggatat tacctgccac ctttcctgca taattactgt taaaaacact aacagctctt 46860 gatttacctt ctctacgaag ccaagtaaag acccctgttt cggggtcata gtgcagcagc 46920 tcctttaaac gtttttgtaa aattaaatcc attaatcaat gtacctccaa ccagctctta 46980 ccaacctttg ctgtaccagt tacaagtgtt tctttcctca aacctaagtt ttttgaagct 47040 tgtccataca tccagtcagc aattgctttc atatcctgtg tcataccctc tggacattcc 47100 caactatttt catcgtgata tgccagaagt aaccttgctc cgatagctgg ttttcgagca 47160 ttcagttttg tcaggccatc ttcacaggct tttcttgctg ctaggttgat agcctcattc 47220 tgaatctgtg cttccgaact catcaggagg tagttcagta gtttatgtgg agatttgcac 47280 catatccatg ctccagcgac cctgatataa ccacctttag caattgaaga attcttccca 47340 aaaacctctt ccagagcctt tttagacgcc ttaaaatcgg cttctaagct atcaagtaac 47400 ttcttaatct ttggcagacg catatagtaa gtttgtttag tcaatgcacc ctcttccgta 47460 gatgatgcct tgatagtttt tgcaaacttc tcgtctccgg ctccaaataa cagggcgtag 47520 atgccatttt tgctcttctt acgacctttt gtaatctcgt gaagaagttc ctcatcctgt 47580 gtctccctgc aacgaacaat atcctcttct ttgttaagac caaagtaaat actgttcagt 47640 gtatgcgcat cagtccctgt gtagacttca tagaggtcat tttcagcatc ataacgcaga 47700 tacttgtcag tttctgggtt aagatacttg tcaagatgtt tacagtagta tctaccatca 47760 tcttgcttag tgaactccac tgactcttta ccctcagtta ccgctttagt gaagtcttca 47820 tcacccataa agttacaaag gagaactagc tgggctgagt tttggtcaac agaaacaatg 47880 ttagtcccct cttcacaaat ccacactgcc ctcataggtg ctccgtagac agcagcacca 47940 gacggtacgt ttacaatacc atactgtgtc atacgtccag ttgaagtacc aaacaccatt 48000 gcaccagcac taaggcgacc atcaggacga atctggttca accaaccttt ttcatcatcc 48060 tttgagttct caatagttct gcgtcggtgc atcaaagtat agtactttgc aatcttctgt 48120 ccaagttcac cttcaatcgt atcataagat gactcagtaa gctttggtga agtacggatt 48180 aagcaaggct caagcaaatc tgtgtacttc ttcacagacc agttatgctc aatgtactgt 48240 ataccttcat gttcaacata actcaaacca caccgctcaa ccatttcctg ccacttagga 48300 tgttttgtaa tcatcttttt attgtctttg aaacgacaaa ctttgacagg gcgaccgtct 48360 gagtctttct tgtagttcca gtcatctgga atccaaccaa ctgatttcaa gtagtcttta 48420 acaacggcta cctgagtcat acgagaaact tcaaactcaa ttggtgtata tggtgcatca 48480 atcaaacctg tgtagcgact tgactcaagt tcaaagtggt taacaacgtg actgttatag 48540 tacttcacag tcttgactgt ttttactggt ttccagtctt tgcatttctt accaatcttt 48600 gcgttcaact cattgcaaat tgcacgagca tccttcattg ctacaaaacc ttccttgtac 48660 tcttcaccag ttacagtgtt ggttggtgta tagcaatttc tcttttcaat gttaaaaatc 48720 tttgtagttg gcttaccaaa tggtttaatt tcgtatgtct gcatctcacc attacgtacc 48780 tgctgacgat actttgtctt agggtacttg gtaattctct tcagtccatc tgcatgacca 48840 aatgtttcaa catactcatt ccaagctttt gcaaactctt ctccagtgac tttacctttg 48900 gtcttaatag ttggaggcag gtgtggttca acctctgaag caagctcatt agtcaacttg 48960 tcaagttcct ttacatggaa ctccataagc tctttatcag ctttccagcc attgatagct 49020 tgttgactca tccagaaaga tgtttcttta gctcgcatat aggtttcata agtgtctatg 49080 ccacacttct ttagcttcag atattcatta tccagtgcgc gtttagtttt ggcgttaata 49140 cggatatctt ctacaacacg agtgaagatt tctgcattcc acacacccca atgttcaatc 49200 tctggtttac ggacaccaac acgagcaccc catgcagcca aaccatgagc acctttataa 49260 ccctttggag ttggtctatc catccactga acacgagact ggataagaga atcctgaaag 49320 aaattactcc acggcttgca ctttggatta tcaaagttcc ataaatcagg tgcaatgtga 49380 ttgaaaaccc accagtcata acccagacca ttatggatgc aaagtcgttt tgcctttaac 49440 gcaaactcaa taccttcacg taagccaccc ttgatgtact tggtatactt gtgaccgagg 49500 ataggttcat ctgtaaagac ccatacaggt ggctcttcat cgtcagattt atagtctgcg 49560 aaagccatta cgtgcacttt agtgaactca aggagtaaac catcagtttc tgtatcacca 49620 accaaatgta agtttttaaa atctacgttt tccattttta ctccctctaa aatcattaac 49680 ctcatacatt actgcaaaaa attataaaaa gcaagttgac aatgcacttg acaaggtgtt 49740 aatctttgcg aagtgggttt ttacttaaaa ggttacttaa cagtttaaat atacagatac 49800 tttaaaactc ttaaaagatt atttaatagc ttttaaaaag ctttaaagta taacgtatag 49860 aatacgttaa gataaaagat taaaacttaa tagttactta aaagaggctt acatgcagaa 49920 aatgtttgtt cacccagaca tagctgactt tgttagagct ttgcagaagt tggaagaact 49980 tgacattgct gctcaacggg aatatgctca ccatcacagg agaatggttg atatacaaca 50040 tgaaatagag ttgtctgaaa actatgaaga tgacttaaaa tgctctgtat ttgagcatat 50100 gaaagatgtt gctacagcga gacgtaaagc taaagacaca gttgctttac tagattctct 50160 taaaaagagg ttgcaaagtg gtacagacct gtgtaatcta gcatcactga ttaacgatgt 50220 tgaaacttct tgggataggc actattatcc acgttctgaa aagacacttg acttttcttc 50280 atccgaaaac ttaaaatgtt ctagaaagaa actcaaccaa ctgagagaga aataatatga 50340 atatcaatgt agaaaagatg cttgaagaaa aaggtattga cgaagcgttc ttaatcaatg 50400 ccgtagaaag catggctatg attcttcgtg gcaacaacta cacagaacag tttatgcctg 50460 caagctataa cttgcctaaa gataagtctg ataacggtgc ttttgcagaa caggttaata 50520 tgatgctgtg tgataaaaca cttgctttag catctatcgt tgtaggtgtt gatgctcttg 50580 cagagttcat tttttatgag atgcagaaaa atgactatat tgccatgacc tctgaagaaa 50640 aagactcgct actgctctta ggttatgatg agctagttaa cctgttaatt tcgtcaacga 50700 gtgctgttat ggctgctctt gagaagcgaa tggaagagaa gctgtcacga tatgaaaagc 50760 ttgattgggg tgtagaagag ttaaacccac gaatcaaaga gattatccag caaaccaaag 50820 attctttgga agaagctgtg aaaaatgatt ctgtagctga catagagcca cttcaggtga 50880 aagttgcatt gatgattcca gccatctcca cgatgatgaa tatcgttgca ctaatccagc 50940 tttcacagat gatgggcaca agcattgagt tcattgagag tatgactggt ggtgtgagta 51000 tgcaagcaat caatgatgtt ctggtgagca ttggtgcttc aatcattgaa gagaagctgc 51060 gcattaactt tggtgatgat tttgtgaagc aaatctcagc tatggctgaa aaagagtatt 51120 cacaggctaa tactgaccaa ctgcactaag tctttataaa ttttacaagc ctccttagtt 51180 gggggctttt tagtaattaa gggagataaa atgagtaata ttatcgcatt tactggaaag 51240 gcacgttctg gaaaagacac ctcatgttct attgtgaaga atatcttaga ggatgagtac 51300 ggctacaatg ttgcagtaat ggcctatgca gacaacctta aactctctgc ttcaaagata 51360 tttgacctga cttggaatga cctgtacggt gaaactaaag agactccaca ggtttttgat 51420 ttatcatact ctgaacttat gcctaaagtt acggaggcta tcgagttcac cttcagagat 51480 gaacgttatc atatggactt taagcttatg tcagagttaa ccggacgatt agtcatggag 51540 cttaagaagg tcgctaaacc gactctattg acacgtctag ggtttagtaa aaagtataaa 51600 ttctcatcaa ggcaaattca acagatttgg ggtactgaag tcatccgtaa agttatgggt 51660 gacaaattct gggctaaaga ccttgaaaaa cgaatggctc gcttctttga atcttgttca 51720 cttatgaatc aagagggtgt tgttttaatc agtgacttaa ggtttgactc tgaagcggag 51780 tggctgagta gatttgcaca ccagactatt gaagtaaaaa gagacaatgt ggataaggtt 51840 tcatcacatg tttcagaaaa tgggatttct accaaatatg cgcgtgacat tatccataat 51900 aatggtactc ttgcagacct tgaaagtaag ctaagagcta tccttaaaat ttaaaagaga 51960 gcatgaagat gagagtaaaa gataatttca aagttattga ccatcgttta gtggaactct 52020 catctctttc caatgaggta atgattgaac gtcttaagag agttgaatca cgaaggaaag 52080 agattgcaga tgaaatccat gaactggaca agattgaaaa tggattgaag gcagaactac 52140 aacgaagagg tgctaatgtc taaaggtcgt aaattgaaag aggctggtca gtttgttggt 52200 cattgtgcat gtccacgttg tggttcatca gatgctggtt caatctacca ccatgacgat 52260 gattcttatt cgatgacttg ctttagctgt aacaaaggtt tcccagagtg ggattttgat 52320 aaaggacaga ttgtgagcac ttattctact ggttcagata ataaaaaccg tactttccgt 52380 gggatggatt tagacgatgt aaaagaaaac cttgaagcaa tggacttgaa agacaggaag 52440 attcctgcaa aagttcttga acgcttaggt atcaaggtcg acattgacag tgatggtgaa 52500 attgatgcac atttctatcc gacttacaaa cgtaatgaag atggcaagct agaacatgtt 52560 ggctaccgtg ttcgtcaccg ttacccagaa gaccatccaa aagaacacct acgtggtaag 52620 ttaaaagact tttcaggtgg tgttggagac attaaaggtg aactggcaat gttcggttca 52680 tggattgctc cagaaggtgg caaccgtcta ttcatctggg aaggtgagat ggagtgtgct 52740 acagcaatct acatgacttc tctggcaatt aaagacaagt ctcgtcgtaa gaactactgt 52800 cacgtatctg ttccatcagg tgcaaacatt aagtctatca aagacaacta tcagtacatt 52860 acatcatttg atgagattta cttgtgcttt gataacgatg aagcaggtgc taaagcaaca 52920 aaagaggctg ctggcatcct acctattgag aaggttcgtt tattccagta tccagaaggt 52980 gtaaaagacc ttaatgaatg gtggacaaag ttctataaag agaaagacac agttctggaa 53040 ggatttaagc agcgtatcta caatgcacct cgttattgcc ctgctggtat caagaacttt 53100 gcagatggtt ttgaggcaat gaagaatcgt ggtcagattc cattgattcc tttcccagaa 53160 tctttcgggg atttgaacag actaacttac ggtggttatg gtttaggaga gattacaact 53220 ctggcagcac catcttcagt aggtaaatca gcttacactc gtgagatgat ttattcagct 53280 tggaaggaaa ccgattacaa tattggtgta attccggtag aagatactta cgaagaactt 53340 atggaaatgc tctgtgcaat ccacctgagc aagcagattt ctgagattcc ttatgatgaa 53400 cgtgattggg atgaactaaa gagagcacac gcagaactat ctaaaggtcg tcgtatccat 53460 atcgttgacc atcaaggggc aattgaccaa gataacctgc tggaatttgt tgactatctt 53520 gttaatagtt tagactgtaa gattatcatt cttgacccta ttacgttggc tctgtcacgt 53580 tcagatactg atgaagagga agttttgtct gagctattgc gtcgttgcaa acgctaccag 53640 tatgcacagg taaacgtctg tcacgttcgt aagagtgcag gtggtcagaa ggctaactct 53700 gaaggtgggg atatctctga agaggatatt aaaggttctg gtgcgtattt ccagatttct 53760 atgaacaaca tcctgttaat gcgtaacaag gttgacccag accctgttaa gaaaaacttg 53820 acaaaaatca agctaactaa atgtcgtcgg catggtaagt caacgggtat tgctggtcat 53880 acttggtaca atccagatac aggacgcctc atcaaagcat ctggttgtgg agttgacatt 53940 gatggtgcag cagaaaatat tcgccaacag tttggtattg gtgaagtgga agaccattac 54000 gatgactctt tgccacatta tgaggatgaa gtgtttgacc gtgagactgg tgaagtctat 54060 actgaagagc agcgtcaaag ctcaacaatt ccacctgtat taagtgagga tgcagatgac 54120 tgcccattcg aaactgagtg atagttataa aagagagggg ttcataccct tctttgaaga 54180 aaaaagttta aataaatttc aggaagagtg tttgacaaag attgataggt tctatagaat 54240 gctcctcatg aaatgtgatg gggaggttgc tataaaagaa gattcctacc aaagcacgat 54300 tacagtcatc attacactgc ctcagcataa tattagttgg ctgtttataa ttaaagaaaa 54360 tgtgtttgaa tatcaagtat atcggagaat accatgaaac actctaaagc atttgaaaaa 54420 gtttttgggg attccttaaa agccactgct ggaaaaccag caaaatacta tgaagaaaaa 54480 cgtgtaagaa ctggaaaaac tgcacgtaaa gcagcttcta aagataagca caacttccag 54540 taattagtat ttgacaatag agtatcaaca aactagaatt ggtactcttc ataaattgag 54600 atagaggttt aaataatgtc taaagttgtt aaaatgaaag ctccggtaga gaaatacaat 54660 ggtactgaac gccaaactct gcgatacctg ctgaaagatg tctggtttta ttacctgaac 54720 acttcaccac gtccgggaaa aggtaagtct attgataaga aattcccagg caaagactgt 54780 aactacagcg tatcaattct ggcagaagac ggtaacaagc tgtttaaaga atttactaag 54840 tctaagaaaa acccagaagg ttgggataaa gttactactg aagcagttga tgcagatgac 54900 ttcgaagaga agtttggttg caaaccacca tttgaagcag atacttacta catcttgaaa 54960 gtaagtcgtg cagcagctta taaagatggt gctgtatgga cagctaaaca gtcattccct 55020 gtaatgctga ttgaagaagt aaatggtaag cgtgtagctg ttaagcagcc gatgaagaaa 55080 atcaaagctc aagcatctga taaacatgaa gatgacaaga actatgatgt aattcatcca 55140 gatattgcag ttggtaacgg ttcttttggt agcgtgattc tttctactca cttctacact 55200 tttgagaaca atgttctgac aaaacctatt caggaacagt ttatcattga tactcttgta 55260 ccttacactg gtggtaacgg tgctaacgga gaacctgaac tggatgaaga cgaactggct 55320 atgcttggtc ttgatggtgt cgaagataac ggtgaaatca ctgaagaaga cgcaacagac 55380 cataaatctt cgaatgattc tgatgatggt gatgatgaag atttgccaga cccagatgac 55440 gaagaagatg aagacttcga tacagaagat taatctctaa agttacttta aagccctgta 55500 ctccgtatgg ggctttttca tatggagagc cataatggag aagtacacat taacaaaact 55560 tcccgattca gttacacatg tttttattga ctctgacagt attgcctata aaggtgcttg 55620 tgtagttgag aaagcaaagt ataaatatgt caataaactc acagcagaag agtctgagcc 55680 atttgataat gcgaaagatg ctgcaagatg gttagcagac cagagaatcc ttgtggaaga 55740 gcttggcctg acatttgatg aagatgaatg ggaaagacag acttggaaag aagctaagag 55800 tgaaaaagaa gctatcatgg ctactcaaca ggtgcttcag gaatggctta aggttgttgg 55860 taaagagaga acttgggtag gttacttaac agagaaaggt gtgcataaac acaaagacat 55920 taaaggtctt gagcaccaat atcaaggtaa ccgcaaagat gctgtcacac caacacactt 55980 agttgcttgt cgtgagtatc ttctgtcaag accagagttc aagctgattc ttgatggatt 56040 tgaagctgac tctatcgtaa ttgctaaagc tgaaaagatg ggtaaaaagg ctgccttaat 56100 gagtattgat aaagaccttc gacaagctga aggtacttac tgcattgaca tgacctatga 56160 aaaatcacct ttaattttta ttgctgataa caatgttggt gaaatctggg attgtccaat 56220 aaaatcgaca ccaaaagcta agaagacagt tggggtaggt tttaaatttc tttgttacca 56280 agctgtggct ggtgataatg ctgataatta ttttggttta aagggcgttg gtaaggctac 56340 tgtaatgaaa gcccttgaag ggaaaacaac ttacaaagag tgtcttgatg ctatctatga 56400 actttatgct aagaaagagt catacactta tgtctcgtgg gatggtcaaa caattaccag 56460 aacaccttta gagttaatgc agcaacactt tttcttagct tatcaggaaa gaaacaagaa 56520 agatgatttc acttttaaga aatataattg ggagccttgt atgaatgaag attaaaggat 56580 ttggtaattg ccccacctat ggtcattggg tatctttatg tggggaagtt gaccccacta 56640 aacattttgg ttttgtctat ttagtacact gtaagaaaac cggacaatat tatataggaa 56700 ggaaacagtt taacagtgtt accaaaagaa aagttgctgg aaagactcgg aagaaggtag 56760 tcactaagga gagtgattgg atgacttatg agacttcttc tgagtatatt aaaaaagata 56820 ttgagagctt tggaaaagaa ttttttgact tttacatcat tcaaacctac tacacaaaag 56880 gtggcctagt ctatggtgaa gcaaaccttc aacataaatt cgatgtaatg acaaaaagga 56940 ttgactcgaa gctcagactc ttctacaatg ccaatattgc agcaattaag tttattacta 57000 aagaaactta tgaagatgct gaaaaaagaa tccataaggt aatgaaagca aattgtgctt 57060 gataactatt gagagagaat aaaatgttta acaaaagtaa agctgtgagc catgtagcaa 57120 aagttgacag caagattgaa gaacttgagc gcattcttgc aaatgccaga gagtcaataa 57180 ttaaagaagt tgaagctgtt gaatctcaaa tgcagcacct aatgcttaaa cgtcaagagt 57240 tacgtgagca tctggaatat attgaaacac gagagctaaa agttaacaga tttttaagga 57300 gccaaaatgt ttaactcaag agagtcagta aaaaactgga accttcgttg tggaaacact 57360 caaaagcaac cttacagtga tgagtattgg gaatctttaa aatctcaatc tctgtgtatg 57420 cttgaagaag caaaagagct tgtaaaagca attgaagaga aagaccccat tgagacactg 57480 gatgctcagg cagatttgca atatgttctt gatggcttga tttatctgtc acaacatgac 57540 cataatggcg ctatgaaagc tgtttgccat aataatgacc tgaagtacac agacgactat 57600 gaagaagctt taaaacgtct tgcagatatt gagaagcgta ctggtcaaga gtgtatcatc 57660 agaatgtcag tagttgatgg taaagaatgg tatgcaattg ttcgtgcagc cgatgggaag 57720 attatgaagc aatctaatct ccctaaagtt cagcttggtg aatacattgt agaacttgaa 57780 agccaagaac tttttgtggt agtatctgac acatgcgtta tctgcaaagg tattgtatgt 57840 agcttaaagg atttgggtgt agatggtttt gtagaagtta atccaattac ctctaaagca 57900 gataaagatt tctgtaaaga gaatggacta tggattgcag atattgtcta ctatgatggt 57960 gagcagttcc atgtaacctc atacccgaaa ctgaattatg atgctaataa cctgaagtgc 58020 tggttaaaag gggttggtta taatggattc acagaacatt aataaagaag gtgtggctca 58080 gaagagccac ttctcaaact acaatatttc tatgacggtg tttatgaatg acccgttact 58140 tgagaagtat ggtgagactc cagatacact tctggataat gaacaagttt taaaagcagt 58200 cctgtacaaa tacgggattg atattgagaa agagtattct tttgaaatct gtcaacacag 58260 gaatactttt ggtaaagttg taatggctcc actcttcatg ggtgtagaaa ggactgacta 58320 tggttggtta tatctaaaaa gaaacttgga gaaataccgt gtctaaagca aaaaagttat 58380 cttatgatga cattatctca ggtgctaaat taggtgttga tagtatcgga caagatgtta 58440 agcacggaga cacagttatg tactgtgacg accgaagagg cagaagtcca atcttgtttg 58500 gaagagttgt ttgcaagatg cgaggtaatt atgttgtttc agatatggat gtcaacgtcg 58560 cacaaaagct caaaacaatc atggatagca agatttcatc atggctctta aattgtatgc 58620 acgcatcgtc aatcacaaag gtaagtgata agttttacga tatgtggcag aatgagcaaa 58680 ttttcaagat ttaaactagg gagcctcttc ggaggctctt ttcatctgta ggatttaaaa 58740 atgattaaga caattaaaaa atcaaacggt acagtagtaa gctttgaccc agaaagactg 58800 aataaatggg catcatgggc agataagcgt ggaattatct ggtcagaagt cactatggaa 58860 gctatgaaac gtgtctatga aggttgcacc acaaaagaga tgcaccaagc catgattgat 58920 gtttgtgttg ataagcaaac tcaagagtac tcagatatgg ctggacggct acttctggga 58980 attatctaca aagaagcctt tggaggtttt actaaggttc ctacgctggt taccttcgtt 59040 aaaaatatgg agagagcagg actttgggag aagatggatt attcacagga agagcttgaa 59100 tacctgcaag gttacatcgt gcactcaaaa gatatctctt acggttatgc agtcttgaaa 59160 cagttcagag acaagtatgg tatccgtgat attaaaactg gaaggctttt tgagtcacct 59220 caatttatgt ttatgggtat ggctatgaaa gcctttgaga agcaaccaaa gcaccgtaga 59280 ctgcaagatg ttatcaagct gtacacttac ctatctgacc tgaagattaa cgctcctacg 59340 ccttatttaa acggtttaag agcaactaaa tcaggctatg cgtcatgctg tttgattaag 59400 gcaaatgata ctgctgaatc acttggtatt gctgcaaagg ttgcttatga catgactaca 59460 aagcaagctg gtattggtat gttgatggag actcgcacta ttggtgatgg tatccgtcaa 59520 aatactattg agcacatggg taagctacct tattacaagc ttgtacgttc atctgtagag 59580 gcaaacaaac agaagagtcg tggtggttca gctaataact tctacactgc tctagacccg 59640 cagattgaag atttactgcg tttgaagcac cctacaacgg ttccttctaa acgtattaat 59700 gagatggact actcattcgg tacaaacgat tatttctggc agtgtgttca gtatgataca 59760 gattggttgc tattctctta caaagatgca ccaaaactct atgacatgtt ctacacagca 59820 tctgctgatg agtttgctat ggcagttggt catgcagtac attcaggtgt taaacacaga 59880 cgagtcaagg ctcgtgaaat tgctaagctg tttattcaac agcgttatgc tacaggtcgt 59940 gtgtatccat tcttcactaa caatgcaaac acacatacac catttaaaga gcctttgaag 60000 atgtcaaatc tttgcatgga aattgtgttg ccagtgtacg gctttgagaa agagacagac 60060 ctttacagag acgatgctgt gaaggaggat ggtgaggtag ctctttgctt cctagctagt 60120 ttggttgcag ggagaatttc agaagatgaa tacgctgacg ttgcttatta tgctcttgca 60180 atggttgact ccgttattga ccttatggat tatccgtatc cgtcgatgcg taaccatgtt 60240 cagaagcgtc gctctgttgg cattggcctt acaaatgtgg ctcattacct tgcgaagaac 60300 tacgtgaact actcttcacg agcaggtaaa acgaaacttc atgaacttgc agagatgcac 60360 tcttactatc tgcatgaagc ctctctgaga cttgctaaag agcgtggcgt tccagagtac 60420 atgaagttca ctaagtatcc tgaaggctgg gttcctccaa agacagctaa caagaagatt 60480 gatgaaaagc atgatgcaaa actacgatat gattgggatg acttagcaca acgtatcaaa 60540 gaaaatggtg gaatccgaaa ctctgtatta gaagcttaca tgcctaatga gagttcttca 60600 ctagcaacta atacgacaaa tggcttgtac ccaattcgtg actttatttt aactaaaaag 60660 tctgcaactg gtaacgtact gtttattgtt ccagattatg aagaactgaa gtatgtctat 60720 gaaattgctt gggatattga cacctttgat atgattgatt gttatgcaat tgttcaaaag 60780 ttcactggtc aggctatctc ttcagacttc tatgttgact atgcaaagtc taagaaggta 60840 tcattggctc aagctttgaa gtacatgatt tatgccaact cggtaggtat gaaaaccatg 60900 tactacctta acagtcgcat tggtgtaggt aaatctgcac tgcaagatgc ttattgcgag 60960 ggttgtggtg tttagtttta acaactatga gggtcgtaaa agaccctcta aaaataactt 61020 tggagagacc atgaaagatt taatagaaaa acatgagcga cctatatact tgctccataa 61080 gcctcggaaa acgatgtact atgtgagtag cacagacatg atgataaaac aaaatgatga 61140 ctcatgggtc gatggcgtct cttacatctt tacagcagat ggtaaaatct acgcaagacc 61200 ttatgagatg tttaacaaag aaaactggga agttttagac agaaaacaag ccctagaaat 61260 gataaagaaa ggagaaatca cgctatgatt aaccagcacc caatcttttt aggtggtgag 61320 agaaaaactt ttgactcact taataaacac tacccaaaaa tctttgaact ttataaacaa 61380 caaaaagcac aagactggtc agaagatgag ttcccttttg aacaatcacg tcttgatttt 61440 gagagtgtcc cagcatcaat gtcaggtgta atgcttgaga ttcttaagtg gcagtgggaa 61500 gcagataccc aagttgctaa gagcttggca tttgcctttg caccctttat ctctgatgac 61560 atctatgcaa ctgcaattat gaagcagtct gagattgaaa acctacatgc tcttacttac 61620 tcagagattg taaggcaatg tattaaaaac cctgaaacca tcttagatga gattaaccag 61680 aatgttgctg tgcaagaccg attaaaaact gtgaatcgtg ttcttgaaga attactggat 61740 gaaggtataa actaccgtct gagttatgtg cgtgattcac ttctggacaa agacccttta 61800 cacttccata aagtgattct gaaaggtcta tttgcagtga ctgcactgga aggtatatct 61860 tttatggcat cctttgcatg tacttttgca cttgatgctc aagataaatt tcagggtatt 61920 gctcaagctg tccagaaaat tatgcttgac gaaatccttc acactaaaat tgatattgaa 61980 gttttaaaag aaactttaag agatgatgag tggcagaaag cttttcaaca aattcttcca 62040 gagattaaag taatcttaga tgaagtagtt gaaagtgaag agaaatggtc gtattatatc 62100 ttctccgaag gacgtgctgt agttggccta aatacaaagc ttcttcatga gtgggtttac 62160 tataatgctg ccccactgta tgatatgttt ggcattcaaa gagattttgt agctcctaaa 62220 gaaccacctt tgaaatatat gattaagaag atggaaattg ataaagagca gaatgctaat 62280 caggagcaac agaatggcgc gtacctattg aatactgttg tagatgattt gaatagtgga 62340 tttttagagg ttccttaatg acttatgtaa tttactccaa agctggatgc cctcagtgtg 62400 agactgcaaa gaattttgca aaagctcgtg gtattggcca tgttgtgaga atgttagggc 62460 aggattatga actatcagac ctgatggaga ttgcacagat gccagttcgt cagatgccat 62520 tcatcatgaa aactgatgga caaaacctaa aacctgttgg gacgctacag aattttatgg 62580 cagaggtgaa taatgcttaa acgcatttgg gaaggtttgg ttgttgatgc accagctatt 62640 gtgattggta tgcttattgt taacctattt actgactttg aacaaggttc attgtttgga 62700 gccatgttac tatgggttat ctttgaaata ttagagatac agttaggtat cactgaaaaa 62760 ctaagaaaac tctttgtgaa gttttctaaa aagatttaaa atgaaagggt ctcttcggag 62820 acctttttag catgtaaagg ggcaataatg aacaaagtac agattattaa aaagagtggc 62880 tcactcgaag aacctgatat caaaaaagtt ttagcagcag tcacaaagtc agctaatagg 62940 gttggttata aagagcttcc accagatgtt actcaagctc ttgagtcagc atttatgagg 63000 attctggtaa aatctactaa gcagaataat ttactcgttt cagtaaatga tattcacagt 63060 attgttgagg gtgctttggc agaagtcaat cacgagattt atgagtctta ctcaacatat 63120 agaaattacc gtaaagaagt tgctcaaaat tgggatgaac tttaccagaa gaccaaagat 63180 acactcttct taggtgacag agagaatgct aactttgaca gcagtttaat ttctacaaaa 63240 ggttcaatta ttcgtggtta tctgactaaa gaaatcttta aacagtacca tttaacacca 63300 gaggaacttg aagccattga aaaagggttt atctatatcc atgatttaag agacctaatt 63360 tttggtggta tcaactgttg cctgtttgac attggtaaag tcctgaaagg tggctttgaa 63420 atgtctggca tcgaatattg tgaaccaaag tctgtactgt cagccttaca ggttattggt 63480 gatgtagttc tttcagcaac tgcacagcaa tttggtggct ttactttagc agagattgat 63540 aaggtacttg taccgtatgc taagaagtct ctacgctatc atgctgagaa agcagcatct 63600 tatggtattc ctaaagaaca ttaccacaat tatgtcatgg agcagctaca gattgaatta 63660 actcaaggct tccagtcact agagatgaaa ctgaatactg taccatgtag tcgtggggat 63720 tttgcattca caactttgac attcgggtta cttgactcag atatgtccaa tgaagataac 63780 cgactgcaat acatgattgc aagtactctc ctagatgttc gtatgaatgg acaaggcaag 63840 agcaagaaac ctgttgtatt ccctaaactg gtttatatct atgaccagaa gagacataat 63900 gagaatatct gtcaaggcca actgtacagc aaagctattg agtgttgctc taaagcgatg 63960 tatccagatt ttttaagtgt atctggtcat ggtgctgtag cagaggcttt tgagcgttct 64020 ggtaaggtaa tttcaccgat gggttaacaa gctctatagc tcatctaaaa cgtgcctaaa 64080 cagggaaact ctacaggtgt agacaatcct gtgctaaatg atgtacgatg taagaaacta 64140 tataacatag gagtcttaca tgccaaataa cttcgaacat gaatttgaat acatctaaat 64200 gccgaacgac taaccgtgat gaatgtagcg gtgtagggtc aagcgactcg aaatggtacg 64260 ctacttagaa ataagtagaa gatatagtct ggacttactg gcgacagtaa gcagcttgaa 64320 taaagcgggt aagcttagcg aacttacctg aacaacaagt gtagagcatt tttatcacca 64380 taccataacg aatatggtga agagttttat gtaggtcgtg caaacattgg tgctgtatca 64440 ttgaacttac caatgattta ccagtattct aaagagaatg gtttagattt ctggaaagag 64500 cttgataagt acctagagat gattcgtagt ttccataaga aacgctatga aatgattgcc 64560 aatatgccag caagttctaa ccctcttgca tttacacaag gtggtctgta caaaggaact 64620 aagaagccta ctgacagggt tggttgggat attgtgaagt ccttcacagc ttcttttggg 64680 gttactgcgc ttgatgagct atctgttctt gctgaaggta aacgacttca tgaagttgga 64740 agctgtagtt ttgcatacga tgttctggaa tacatcaaca tgaaaactga agagtttaaa 64800 aatgaagatg gcttcttata tgcagtttat ggcactccag cagaatcact ttgtggaact 64860 cagctaaaac agttcagaga tatgtttggt gttatcaaag gtgtttctga taaggaatac 64920 tttacaaaca gtttccatat gaatgttgca gcagatatta caccatttga gaagcaggac 64980 ttagaagaac ctttcttcca tatctgtaga ggtggtagaa tccagtatgt cagagtagct 65040 aacccagaaa acttaccagc acttaaaagt tgtattacaa gagggatgtt gaaaggtttc 65100 tatcagggac ttaactttga cctagcaatc tgtgaacatt gtggtaacag accaaaggct 65160 gatgttgaag aatgtgaggt ttgccattca cacgatatct ctgtgattaa cagggtgtgc 65220 gggtacttgt cattcacaaa aattaaaggt cagtctcgaa tgaatgacgc taagatggca 65280 gaaattaagg atagggtttc tatgtaaaac ttgacatggt ggtgtgagtc ttgataggct 65340 tgcatcacct ttttatttgg agttacatta tggacttgtg gctttatgta gcagtttgtg 65400 ggattgtatg tctgataatc ttatttattc ttggagtaat gcgatttaga gacatcatac 65460 agtcagattt tttgcctgag tttgccatga tagttggggt tattaccctt tgtgtcttgg 65520 cagtgttcta ttcatacaaa actgtgatat ggatggaggc aaacaattgt gtaaaaactc 65580 atcagcatcg tgaggttact cattttgtga gtgtacttag tggtagcacc actatacttg 65640 tcccacaaac ttctgtagag tatctttaca catgtgataa tggtaaaact atatggtgga 65700 attaacaatg acaacactct taaaagtatt gatgcccata ctacatatag cagtcttctt 65760 ctttggtatt agtgttatgg tatggggctt ttcagaccca caatggagtt tttcatatca 65820 tggtcagatg gacttatggt catgcttcaa accattttta gggttagcta tagcattcag 65880 tgcattacca actaaggtga aattatgatt aagttgaacc aaaaacagct agagtggatt 65940 aaagactacg cctcagagtg tggctcttgt gaaaagaacc acctaagata ctcaacattc 66000 catacgacct tcacattgta tattggtgac aatgttctaa gtgactccgt agaagataat 66060 gtagcattac ctaatgagtt gcttgacaaa ttagctgtag tcactggaac ttggtctgaa 66120 gaagacggtc atgaattatc taacgatgtt gtcttctaca gtcttgaaaa cattatgaat 66180 ccagagtaca ttatgttaat gacttgtgca caagactgtg tgccattaca aaacttcatt 66240 aaagaacact gtgaagagtt tattactaaa caggttcctt gtcaggtggt gtttgaatga 66300 gtaaaaggct taaataatat tggtgaggta actagatgaa ttacatggag attagaccat 66360 ttgacacagc taatggtgaa ggggttcgtg taagcctctt cgtagctggc tgcaaacatc 66420 actgtgaagg ctgctttaac agggagtctt ggaaatttaa tgctggtaaa gagtttactt 66480 atgcaaacct ctacggcatc attaagttaa tggatgataa tgctatcagt ggactgtcaa 66540 tacttggtgg ggagcctctg gatgacagaa acattcaaga ggtcactaat atatgcaagc 66600 atattaaaac cgtttatcca gagaagtcta tctggctctg gacaggtttt cagttacacg 66660 aaaaaattca cctagatgtg atgaaatacg ttgacgtggt gattgatggt aagtatgatt 66720 catctaaacc aacagttaag ccgtatcgtg gttctgataa ccaaaacctc tggagaaaag 66780 agtatgggtg gcaaggtgac tgtcagtgga gagccgagta agtctcgtcg taaagtgggt 66840 tacagaaaag gtgagataat ggttctttct tttaacagtg ctttattggg tacttataaa 66900 attaagaccg agctacttga tgaatggaga aagtatacaa actccctttt cggtaatgtt 66960 ggaatggaag ccttagcaga gattgagaag gctggaacat ttgaagttgt tggtaaaggt 67020 aactacacaa tgttctacaa aacaaattta aacgttggtg acagtattgt tggtgtcact 67080 gaagaagaac ttaaaacatt ttgtgaaaag attgagagag atgcgaaatg ggactctgga 67140 acagttttaa atcaaaagta aaagcagcac tagcatcatt aggcatactc actggcattg 67200 atgtgactca tcttatgcag aactttaaga tggatgagaa gctggctaat gagattatga 67260 aaagtatcta tgtaggccgt ggcaaaggtg gtaagaaaca agcccaccgt ccgtctggtg 67320 cagcagctat taaacgagca gctaagaaag ctcgtaaccg taaacgtaat aagaaggcta 67380 aataatcatg agcaaagttt ataacactcg taaattacag attttcgtac tgtgccagtt 67440 tatggctaaa gaatataact tctactattg tggtacaggt tttattagcg atgatgatgg 67500 ctcatacctc ccatttaaag aagctgtgaa actctttaat gaagagaaaa gctctaagaa 67560 agatattgaa aaggttaagc taacctacag caagaaagat aagaagatta tctgcctaga 67620 taactttgtg aaagttactg gagaagcaaa agagtttatg gatgagagtg aaatctcatt 67680 cacaagcatc ttgaaagtag ctcagtaaac agatactata aggggactgt aaaggttccc 67740 tttttatttt ggagataata tgtatctgtc aaatctgaaa cgttctgttg caatgtcagt 67800 gttaagactc agttttgagg aacgtcaaga gttcattgac tcccaccaat acgacccttc 67860 caactccaat cacatgattc tctggaatcg tgagagtact cgtgaaagag cattatttcg 67920 atattatcca cactacacca tagacaacct gtatgaatgt tttgttgtga agaacaccat 67980 taaagtactc aataaacttt gcagatacac aggcagtcaa tccttcacat taggccacca 68040 caaacctgtt acaaaaggtg gtgaacatca ctgtgcaaac tggtttattc agactaaagc 68100 tgataaccag aagcaaggag atagcctcct aagtatccct aagatgacct atgaagagca 68160 agagagatat atcaaaaata atatgccaga tgtgcttgac aacaactata cagatttggc 68220 aatatctctc ctgttgaagt tcgagatagt ttatagggca acttacaatg gctaaagaaa 68280 agtgggagat tttaccatta gtcagtgaag gcggtaatgg ttgtgaaatg tacatgatac 68340 gtggtcatgt tccagagcca attgcacttg agatggtaaa taattataca gatggttcct 68400 gcaaagactt aggagaacca actgtcaagc agcaatgggt aaagcctgtg ccagatagta 68460 caggaaactg tagtgtactt tatcacgttg tagaccctgt aaaatgcaag tctgcaatgg 68520 cagtaactaa cgtaactttt gattgagaga gaaaattatg aaaacatcta tacgtgttac 68580 agttcattca ccaactaaag gaactcatga agaagagttt aacatcatcc aatttccttc 68640 tggtgagatt ggtggacact tttcaccaga gtttgttgat tttactgctt atgcagcatc 68700 atctatcaac aatgtgatta tgattgtaaa aggttatgat aaggacacat tgtttgctgt 68760 ggcacttgct aaagaagcaa ttgatgattt agtacctcat aagtttgcta tgaagactgc 68820 tatcttttac tatttgccaa atgcacgtta cgaccgtcac atgtttaaag gtgatgcagc 68880 agctttgaaa gtgtttgcac aacaggttaa tgcaatgggt tttgatgcag tctgtgcagt 68940 tgaccctcac agctatgtac cagataacct gtttaactgc ttccagagta ttcctcaaaa 69000 ggaaattgca gtccactatg caaatgaccc acgcattgat ttcttggtag ccccagatgc 69060 aggtgcagct aagaagactg aagagactgc taaagaggtg gataaaccat acatcacaat 69120 gtctaaagta cgtaacctta agactggtga aattactggt atgcgaatcc ttgatgatgt 69180 tgatttgacc gataaaactg tcatgattct cgatgatatc tgtgatggtg gtcgaacctt 69240 catagaagca gctaaacatc ttcgtgaagc aggtgcaaaa cgtgtggaac tctatgtaac 69300 tcatggcatt ttctctaaag gtgttgaaaa cttacttgac aatggtattg accatatcta 69360 cactacaaac tctttagggg aagctaaaga ccgtggctta acacattatg cccaagttac 69420 tgtaattacc attgattgaa actttatagg gggtttcaaa gccccatttt gagagagatt 69480 aaaaagatga ctaaatcact ttatgcagta ccagcaggtt taaacgcgga tgcttacaaa 69540 tctggccata tttatcagta tcctagtgca acagagtacc taatgttcaa cctgacacca 69600 cgtagtgaca aatggtttaa cagcccttta gcaattgacg gtgtagtggc ttttggtatt 69660 caacgttttg ttaaagatta cctgatagac cactggaacg ccaccttctt tgaacgtgac 69720 aaaaaagaag caattgacga aatcttagaa gtcatgaacg gtgttctggg taaagatgct 69780 attggtcgag aacattggga agcactccat gacttaggtt atctaccagt tgaagtatac 69840 gctgtagaag aaggcacagt tgttcctatg cgtgtaccaa tgattgtctt ccagaacact 69900 gtctcaggtt tccattgggt agcggggtat ctggaagatg ctttctctgc tgagatttgg 69960 aaggcttgta ccattgcaac tattgcattg cactacaaac gtatctgtaa gaagtggtct 70020 gaccttactt gtgacaacga cttgcatttg ccttatcagt gccatgactt tgctatgcgt 70080 ggtatgtccg gctttaccga tgacgcattt aacgctgtag gccacttaac cagctttaaa 70140 ggaactgata gcttccctgc tgtgtataca gctaaacgca tctatggaca gtcctaccca 70200 atctctgata ttggtagctc tgtaccagcc actgaacact ctgtaatgtg tgcaaacatt 70260 gcttgggaag gtggtagtga gttgattgaa gaagaaagac gctttaaagg tgagttacaa 70320 accttccgtc gtttcttaac agaaacttac ccaactggta ttgcaagtgt tgtttcagac 70380 acttataact tctggagaac tgtatcagtc atattaccag aactccgtaa agagattatg 70440 gaacgtaatg gcaaactagt aattcgtcct gattctggag accctgtaca tattgtcaca 70500 ggatacaaag caatccattt agagtgtgct aaaaaggctt attacgaaca cctaagtaag 70560 ctggaagcca gcgacacaat gctgaatgct gttctgaaca tgaagcttga aaacatcaat 70620 tatggtattg ctggatggct actgtcagaa ggttacgaaa tggttgttga cagagaagac 70680 tttgaagttg ctgatacagt gctgttgaaa aatgcttata tggttggttc tgcaaacgtt 70740 gtaacacgtc ctgtagcgga gattgatgga gctatcaaga cactgtataa catctttgga 70800 ggaactatca actctaaagg ttttaaagta ctggatgagc atatcgggct tatttatggt 70860 gactctatca cgttggaacg tgcaaacgaa atactgaagc gtttgtatga aatgggtttt 70920 gcaagctcta acgtagtatt tggtgtaggt tcttacactt accagtacat gactcgtgac 70980 acttttgcat ttgctgtcaa agcaactctt gcaagtattg gtggtaaaga gattatgctt 71040 gcaaaagacc ctaaaacaga tagtggtgtt aagaagtctg cttttggtgg tgtagcacct 71100 atgtgggatg gtgaaaatct taaagctgta gatggctatg gattccagag ctttgcagat 71160 gcacttgaac acccagcttg tgctttacgt ctagtcttta gcgactctga gcagttcggt 71220 tacacaactc ttggtgatat tcgaaataat attgacaagc agctttaaaa gtatatgata 71280 agaggctcct acgggagcct ttttaatttc tggagaagat tatgaaaatc aaagagatga 71340 acatcaacat tgtcttagaa gagcgttggg agaacatcaa gaagcctgaa aatggtcata 71400 agttcctcaa taaaatctta gtagcagcta aagaagaact gactggcaag attgcagcag 71460 caatcacaat aaaggtctgt gtaaaaggtc ttccagacaa tcaccaattt gcacttgacg 71520 agtttaaaga gagcttctac aatccaaaca aacagatgct tgaaagtaac tttgcagtgt 71580 ctacaagtat cgtccatgac agaagcttta tcctttacaa gaatatgaga ggtgagtcat 71640 gcaagcatat tggatagaaa ttttgctatc acttggtagt gtagcagtgt ttgtttatct 71700 tctttgtaag tactttgcag agtacaagaa gtgtgattac tgcaacggag aagggtatac 71760 aagagcaggt tgttgcccta tgtgtggcgg ttctggtaaa atgtttaata agtaatttaa 71820 cagtaaacta agaggaaagt attatgcgca tggtaaatga ccacgcagaa gtgattaaga 71880 gttcaacttc tttagagacg tctcaagcac agattacaat gacacctgag atgttcagcc 71940 ttttgagttc tggtgtatat acctttaaag aaagggcagt gattcgtgaa ctgtcatgta 72000 acgcagtaga tgctcagaaa gaagctggaa aagagaacat cccgttccat gtgcatttac 72060 ctactcgttt tgagccttac tttgaagttc gtgattttgg aactggattg actcatgata 72120 aagttatgag tttgtaccta aactacgggg cttctacgaa gaatgactct aatgactaca 72180 ttggtgcaat gggtatcggc tcaaaatccc catttgcaat tgctcagtca ttcacagtat 72240 ccagctatgt tgacggtgtt gttaacaagt actctgttta ccttgagaat ggtatccctc 72300 aagtaactaa gctaaccacc aacccaacga atgaacctaa tggtttagct gtacgtgtag 72360 cagttgctga ccatcgtatt tcaaagttct ttgaagaggc tggtaatgta tactcatact 72420 ttgctgtaaa accagaaagt aatattgagt atgacgatgt attagcagat atgaacgtca 72480 ttgcccgtga agaaggtgtc tatgatgcca tgattcataa gcaaagctgg cgttctagtg 72540 gtaacaggac agagtttaat gtggtgatgg gtaacattgc ctaccctgtt aatatggaag 72600 cattacttgg tgatgatttc ttcaaagtat tgccagaatt tttccgtagg agcgtagacc 72660 ttgtaaacat ctacatgcct attggttcag ttgctattgc agcttctcgt gaagcattgc 72720 agatgaatga cacgacaaaa aatgttatca ttgaggctac taaaaagata actgaagcaa 72780 ttacaaagga tgttatcaag aaagttaata gccaacctac actcatggat gctgcacagg 72840 cttatgctga gttacgtttg aactcacgag agatgtttaa tgctgtgtgt ccaaagctag 72900 agtggggagg cgttaagctt gattctctgg aagaagaatt actaaacatt cgtcgtggaa 72960 ttatctacgc agaagacggc tcagttgtct atgaacgcga tggtaaaggt aatattaagg 73020 ttgataggaa cggaaacaac atccctaaag tagattatct ttataatcca gttgcttatg 73080 ttaagtttaa ctctttagag agtaagattc gtgcaacagc actttcctac actcaagagg 73140 cgagtatgtt caatatcttt ggtgcaatgc gcaaaagcca aattgaacag tttttgtttg 73200 ttatcaatga ccgtcgcaat aaaaatggta ctgagaagac tgtaggacgc aatcagattc 73260 tgcgtggtgc atgtcgagac tatgccagtg agtcaagtct gtttcacaga tacaatggta 73320 ttgtctttgt attctcgact gaaaaagagt tagacgacct aatcaatctg cacaaacttg 73380 ataaaagctt gttaaagatt gtgaagatgt ctgataagga acaccattat cagcgtaaag 73440 aagctgtaag aggtgttgta aaactttgga aagctgttcc agcagaaggt gtagcttcct 73500 ataaagaggt ttcagaggac tttgatacaa ttgaagaacc tcagttttat attaaggcag 73560 taggcgacac agttgatggc gaatgttttt gctcatctcc agaagatgta gctaagtcag 73620 ttgccaatgt cattggaaag acagtatatg ttttccgaaa agcaaattgg aaaaagatac 73680 cagaagactg gattgaagta gatgagaagc tcttgaacga cagcttaact gatgttcatt 73740 ggattaatca taacagatat atgacacgta tctatatgaa tggtgtcctc gaccttacaa 73800 gcagttggat tattgccaga aactttacgt tcaataacag aaagatttct cgtggttatt 73860 gttattcacg agatacaaac aaaactatct tcttagaagg taatgaagat gctgttgagg 73920 caatgtttgg taaaatccaa tacgttgctg caccgtttgc atacacttac actattagta 73980 ggttgcaaac tttgaaagat tgccttgaca atgatacaaa gctgtacaag aaaattaaga 74040 aagctggtga ccgtatggtc atcaaggtga caaactatct ttcaaaaaga aaacaagaaa 74100 acttcttgct ttctcattta gattggaata aagtgtcacc tattgaagtg agtaagttct 74160 taggctttga tgtgaagtgt gttccagaag gaactacaat ttacgattaa agtgtttgac 74220 aaggggcttc aaagcccctt agaatagcct tacaaaatga tttattaact aacaagagag 74280 agtaataaga tgactactaa aactaaagca cagattgacg cagaaattta caaactggtt 74340 aaagaaggca agctgactaa aacagctatt gcacagaagt tcaatacttc aacccgttca 74400 gttggtcgtg ctgtagagcg tcatgaagca accttaaagg gtaagaaaaa gacagcttcg 74460 acaccagcta cgaagacttt gaagcaagtt gctaagacct ttaagaagaa agctggcaaa 74520 ccagttgaaa aggtcgttaa agacactgta cagaaagttc cagtaaataa actgcacgaa 74580 gctatgcaga aagatgacaa gattgagtac atgattactg gcgactctgt aattatgact 74640 tacggttcag aatctgaaat tgttgagtct actcatccga actatcaaga gattgtagtc 74700 catgttgtga aaggtgagtt caagaaagct ttcgaactga tgaacattcg taaatctatc 74760 gaaaacttca ctcagggtgc tatcacaatc aaaggtgaca agctattcta cggtgctgtt 74820 gaaatgcgtt ctactctggt tgaccgtatc cttcacatga tgaagactgg tgataaaggt 74880 tttgaacgac ttgtaatgtt cttcgaaaaa ctgatggaaa acccatctaa agactctgta 74940 gaacaacttt ggggattcgt atctcacctt gatgttgaaa ttgatgaaga aggctacatc 75000 attggttgga agaaagtctc tactcgtgaa ggcaagctgg ttgactctca cacctacaaa 75060 gtacctaatg atttaggtaa cattgtagaa atgccacgtt ggatggttga taacaaccgt 75120 aacgtaactt gctctcaggg tcttcatgtt ggtgcttggg attatgttcg ttgcttctca 75180 ggtgatacaa tcctgaaggt tcgtgtccat ccacgagatg ttgtatctgt tccgactgat 75240 tacaacgata tgaagatgcg ttcatcccgt tatgaagttg cagcaatcgt tgataatcaa 75300 cgtaaagtgt tgaaagcatg ggacggtaag actgaagctt tgcatgtcat cgtcggtact 75360 gctggtgaac tcatctccca acgtaaacgt gaaatctaat aagtaatttc ttaaaaggct 75420 gcttcggcgg ccttttttat ttgtattttg tgcagagtgc tgtataattg ttgtcacgat 75480 aaactaaaca ggagaaccaa tgaagaaatt gattctagga ttgtgcttaa tgtttacagc 75540 acatttatct tatgcagttg actgcccaga gctatcaatt agccaaaaag ttaacatgtt 75600 aaaagcttac cagtatggtg agaacaacat ggggaaaggc tggggtatta ctctagcagc 75660 tatagcctta caagagtcag agttaggtct gaaggtagag aataaaaaga cccatgacta 75720 tggtattttc cagaatcact tgaagactgt tgtaaagcgt aacaaaatta gtcctaatgt 75780 ggctaaaaag aaactcttaa aagattttga ctatgcagca aaagagacac ataaagagct 75840 tgagttttgg actaaggtac atggtcaccc gaagtcaaag aagactttac aaaaagtttt 75900 agcatcatat aatgctgggt attcgtacaa aatccctaaa gctaagaaat actctcaaga 75960 tgtctataac aatatgaaag ttattgctca atgtgaattt gcaacaaaca tttctaaggt 76020 aaatcatgaa aaaattaaga aagcctgatg aagtcctgtg ccacgcttat gacttgcatc 76080 ctcatgagtt aggtcttgat tcctgtgtat ggactccaga acagtgcagg gattttgaag 76140 acactgcaag agaagttgta tgttcacttg aagagttcca cacatcagaa ccaattgtga 76200 acgttgtgga taaagaaact ggacaagcta taggtgtaag tcgtgatagt ttagtcatag 76260 tcaataaaga ccttgtagaa aaaggtaacc tcatcttagc agatattgat ggtgttctta 76320 caaattttaa tcacgaagat tgctcaacgg aattgactga tgggtcattc tcacagtaca 76380 ctaatcttct tgactctgta agagcaaaac caacatatgt ttttagtatt attgatgcaa 76440 ttgctaatca tgctaccatt ggactcttga cagctagagg tgaatctcag agaataccta 76500 ctgagatgtt tttaaggcat aacatagagc atgattacat gctttttatg cgtggttttg 76560 gaactaactc tataagtgca gaaagtttaa aagctaggat gattcagtct tgcattcttc 76620 cttactttaa tatagtatgc tttatagaag atacagagaa gaatgttcag aaggtaaaca 76680 gaatccttcc acacattaaa accatgttag ctaaacattg agagaaaaac ttatgaacaa 76740 tatcattacg gtagcactgg acgatacgac aaacaaatct gtagtagttc gtaaattgat 76800 tcaaggtaac tttgaaggta aaatttttcg tgctgtcaat gtaaaagctg atggcagcat 76860 tcgtgaatat cgtgcattgt tgaacgttaa gaagcacgta aaaggtgttg gttcaacgac 76920 tgcacacaaa gaaaacctga tgactatcta tgatatgggt aaggcttcag agttaggtgc 76980 tgaaggtatc gttaaagaag gtgctccgta tcgctctttc aatctggaaa ctactcttat 77040 gctttccttt acgagtggtt ctaaaacaat cacttatctc tttactgatg ctgcaacggt 77100 atctgctatt aaggatggca ctgtcaaagc tggcgtagtt gctgctgcaa aagcttcttc 77160 gatggctgca aatatccttg ctaaagtcct cggttaaggt taagatacag gctccttcgg 77220 gagccttttt catttcagga gattgttaaa tgacatttaa agagttctgt caagctactt 77280 tcataattgt tttcttagtt ggggcaggtg tctggggagg atactcttac agagactacc 77340 aagttgctga agctgagcta aataatgaga aactaataag tgttgctaaa gatgcttatc 77400 aggaaggttt agccacactc agcaccaatt acaaaaatga tttgaaagac gtgcttgcta 77460 agaataagca tacaaaagag gtactaacgt atgaaaagac taagccagag ttttataatg 77520 tttgtgttac tgataattat gtcagggtgt tcaacgaaca aagtgaacag tacattcaaa 77580 aactcccaag taagtgagag tgacaagtac actcaagaag attcaagatt cactgtcaaa 77640 ggtaatactg gtagtgatgt ggcatcagcc cttgagtttt accgtgatgg tttttaccag 77700 tgcacaatca aagctaataa ccttattgat atgattttat taggaaacaa acagcaatga 77760 cagagaatga agacactttc tatgtagaag ggtacttact gctaccacga ccaaaagaaa 77820 cttatatgcg ggttgatttc tcaccaacca ttatggataa cgtgatgtgt catatcttta 77880 tgcaaggtgt cacagcacaa cttaagcatg ttggtaaaga gtgcaaaata aaggttgaca 77940 ctcatccaga aatcaaagag aatcactaca catggttctt accagactct aaagaaatct 78000 tagcagttct taaaacgagg aaatgattat gcaattccag ccaacaaatc gtgggttttc 78060 ttatgcagaa tttaaagatg ctaaaggaga gatttgtact ttacaagaaa gttcatcata 78120 tgaaccatgt atctggttag gtgctaaaga ggtctctgtt cagtacctag atggtggctg 78180 gaaaacactt gatatcccag cattagtagg caaagatttt gtaggtaacc aaagaatgaa 78240 actcaaccaa gaacaggtga gagagttatt accatacctt cagtactttg ctgaaaatgg 78300 tgaattacca gcagaggaac ttacaaatgc agattaatgg aagagatttt gtagccgttt 78360 actacgagaa cgataaagaa gttg 78384 <110> Optipharm.CO., LTD <120> Novel shiga toxin producing Escherichia coli specific          bacteriophage ECOH1 and antibacterial composition comprising the          same <130> 1-65P <160> 1 <170> KoPatentin 3.0 <210> 1 <211> 78384 <212> DNA <213> Unknown <220> <223> Bacteriophage ECOH1 <400> 1 agagatgccc cttaacattt tcttaacaat ttcttaacaa tccctacata gttatgcttt 60 taaggcactt gttagagact tgttagcccc ttgttaaatc tctgttaaga ccacgtaaaa 120 gccttgtaag agtctttagc atagccttta aagcctctgt aaagctctat aaagaggtat 180 ctatacagtt ggggtgtaat tctaggaaga gacttaaaag agcttacaag gagctataga 240 gagcttttaa gagggctatt tagagaatca ctaagaggga aagggaacga taaggaagag 300 atagtgacca tgttaatagc ttgttaaaaa gattaaacac ttgttagaaa cttattaatt 360 accttaacaa aataactctt aaaaattaac ttgttagctc ttgttagtca tctgttaaga 420 ttctgtaaag cactatcaag ccttgttaag aaactgttac gttcttgtta gttatgttaa 480 gaatctgtta agacctttgg agagttgtta agaagatgtg agaactgtta agagattgtt 540 aaggatattt taaaattttg caaagggggt gttaaggagc tgttaagggc taccaagcag 600 atatacatcc tagacagata tttttcagtt ccttcaaaga ccctaaaaaa tgacttgata 660 gtcctatttt ataaaaattt taagattctg aataattacc tagacagtct tttaaaaata 720 caggcataaa caggcttata agataccttg ttagtaccgt gttagacctt gtgagataag 780 gtctgtaaag atattcctgt taagtttgtt aaaacagtct atatagaggc ttagtagtgc 840 ctagtgaaca cctatagaga gtatcatagc tgacatagag attaaggggt gtatagaggc 900 ttctaagagc gtatagagag atggttaagg tgattgtata ggttgttaag atggcttgtt 960 agaagagtgt ttagaaggct tattaaaggg ctatttagaa gggttataca gaggggctat 1020 taagaccact agatagttac taagatacta tatagtatta tataactata tagagagtaa 1080 gattaagaag gttgttaaga aggatagata ttttattcac atatgatggt gacccagagg 1140 ttgggacaac cgataaaatt ttataaaaat taaaaagccc ccaattaagg aggctcttaa 1200 gatattttaa atcagtgttt ccagaactgt ttttagtgat gacttggttg tctgataaaa 1260 atgagtaaag ccattgttgt tatcaaatac ctgcatcatg atatcatctc ccttgattgg 1320 gtacactcgg atatcatagt ggaaaccatt aaagacacaa gagccattac agaatgcact 1380 aaagtcatcc actgagatat actcttcatg tcctgtgatt tttatacaga tacctttact 1440 cggtctctta ggattaatat cttccatcac agacatattc tgtccaccaa gagataccat 1500 agtgaccact ttacggttct tctgtttaaa gtacatctta actttctgca aagtgtcttc 1560 atagaacgga taagacttct ctacaaagat tccttcaagt ggctctttac cattttcaac 1620 ttctctggta tgccgtactg caaagataat ttgttggaac cagtcaagat tttcttcgga 1680 gagtgcttct cgaacatcac tccagtcaag aactaggtag ttgccttcaa cttcttttaa 1740 gttatctttt tccatatcta tcacaccatt atcgtaaaac ttggtaagct ggtactgcaa 1800 acttgttgct attgttccta ataaggtctt cttctgttac taagaatgta atcccacata 1860 agtgcgtata gtggctgtca tactcaaata ttttaagtaa gtatttacca tcatgataaa 1920 cagattctac tacacctttt gcaacaatct ttccagtctt gaagtcttta agagggtatg 1980 tattaccaac tttagggact gttttcactt caggttcttt tagcttctca ctagcttcta 2040 catcacctag taagttagaa ctttcaaaag ctctgaatct catataagct tctgaacatt 2100 cccagataaa acaatgtaca agaaccttag cagcatgtct tgagcaattc aactcatcac 2160 agatttcttt gtacatttca tctttagttg aattggtaag cattgctttt cgaactgttt 2220 ctttaatttt cataagctct ccgaataacc ctattaagca tctctaaagt cagctttcca 2280 gattctaaat gtggcacaat aagttttaaa gctttttcaa catcatgcac aacatctatt 2340 ataccttctg cataggcttc tacaaggata tcttttacat tttgtgattt acctttttgt 2400 ggtatcacta gacgcatatc aaactcattt gcttgaggat ggttcttacc ttgccaataa 2460 ccatctttgt taaagctgat gtagtcaccg tggtaaaaat gtacaccatt agctttaaac 2520 ttctccagca caaggcattg aattgggtat tcagtattcc actccctgac tcctataacc 2580 ttcactgttg cgatgtactc ctgtgttttt gcatctatga tgtcaagttc ttgaccagct 2640 atgatttgca tattcgctac cttctaagtt ctacaaaggg gctatcaagt aacccctcaa 2700 gttattactc agacttttca gtcttcttgt cggatttctt actagtcttc ttctcagctt 2760 tctgctcagg ctccttctca gaagttgcct tgataaccat atcaagaagc tctgataagt 2820 cactcttcag taaagtaaca ggctgctcgt tgtagaagtt tttgtcaaga taaactttga 2880 actcttctat agaaggaaat ccaaaaattg gtacaggtgt cttaatcatt acttagtctc 2940 tccataggca tcttttaaga ttgccttgtt aatcatttca gcgattgcaa aacgaacaca 3000 tacagctata attgtaggtt gcattcttta cttacctctt caagtttaac ctcagaatcc 3060 ttaagtcgtt tcttatgaac tctgaacctt attagtgaga tgatgataac agctaaagga 3120 acagcataca agtaccaaac agcatatacc tttgcagtaa tctgtgtaat ggtcaagtct 3180 tgagctatac aactgattgc tgatactgcc agtaacattg ctaagaagaa cgccagtacc 3240 ataacaatac ttaggcatcc tctagcatgg tgttcatgct taatgcactt attcttttcg 3300 tcaacaaccc tgttgtagtc atttgtaaag tctctgtaga aagctttcaa gtattcttga 3360 gtgtagcctt caaagcaacc tgtaccatac caataatcac caccaaaatg tgctatgata 3420 ccagtatctc catttggttt agttactctc aaagatgtgt gatgacgagt atcttgatag 3480 tctattttgt atctttcttc gtaaatcatt tcccaacccc tctcaatcgc ttgttccatt 3540 caaggtcaat aaacctttgc aggactttcc ctctaggtgt tacacctttt aaatctgcat 3600 cgtaacaatg gtaaaagtca ccttcagcgt gtttaccata gcattttctg atattctggc 3660 ttctgcgata ctgttctaac aaggacagtt tgtagtaatc ttcaactgta gttagttttt 3720 tcattctttc accgtagtgt ttctccagaa actaaaaagg gaactacctc tcgatagctc 3780 ccatcataat caatattgta tactcggtca agagtatttt ttaggcagta atgcgctacg 3840 cttgttactc tcttcactca atagtgcgat aaattcatca cctttccctt tccacggact 3900 gaatgtaggg atgtgctctc tgatagcctc aatcactgtt ttcagggcat tgttctttaa 3960 ccaccaatca gacactgccg aagctacgat gtagtaagca ccgtcatctg tgaagattgg 4020 ctcagagata catggtgaaa tcatagtggt gatgatagag ccattattca tgtaatatgt 4080 tcttttttca accttatcaa gaagcttgtg aaggtctgca aagagactta ccacctcttt 4140 atggtcaata tctttttcaa gatttgctct atactttaat agtgcagcat caacctcttt 4200 atcattaaat ttgaagtact ggacttcttc attcacacat acactgatgt tgttggtgtt 4260 tatcgtcaat ttgcacagtt tgactggaga gttaatgttg gtctgaaaaa gtgctacaca 4320 gccttctaca tttccgaaat gcttgactaa tgtaacttct ggttggatat gctcatgttc 4380 ttctgacatt acagtttcct cattaaatac tttttaagtt gtgtgttagg tttctcaaaa 4440 acttctatag aagatatctt aacagactca ccacgcatac cagtatgttt gaatatgtag 4500 tactctaaca tccctatgga ctttgctggt aagtcatgct tgacatacac cgttacagaa 4560 tcttcaaatt caacaacttt tgtaccatct ttgtagttga actctttagg atggttgtaa 4620 ttgtctatgt catacattaa aaagagtctt ttccgttgca tatcaagctt gtttgttaaa 4680 gactctttga tatctgagaa gtttttgtaa actgtgacat ggagcttact catcgttaaa 4740 ctctctgacg aagaaatagt tgactttgtt attacctacc ataaggtcaa agcaggtatt 4800 ttcaaaaggt ttgttgtagg catcgtatga aatatatggg tcagctactt gcttagtgct 4860 taacttctta cttgatgggt ttaagaggcc accatacagc ttcttgatag cctcttctac 4920 aacagaccag ataatttcgt cagtaatttc ttcgtacagg tcaagttcac gctctagtga 4980 gaagtcacaa atagggaaaa taacctgtac tttactcatt aacgaataac ctgtgtgact 5040 tgaattgctt cagttactga taagtcacct actttctctt ctttgataaa ggtgaaggtg 5100 agttcaacag gttcttgctc ttcttgctca actggaatgc cattaagctc atcaaagatt 5160 gattgagttg tccagtcttc tccaccatct ggatagtgga ttgcataaag aggaaattcc 5220 acgtcatacc agccaaatac agggcaaccg tctacatcat cacgtactcg tcgaagagtg 5280 ttgcctgatt ctgtaaatcg aaggctgaga ttaccattac actcaaaaat tactgcatca 5340 gcaggcccaa cattttctcg accatcatga ccaaatgtgt caacctttac ttgaatctcg 5400 ttattcataa aaacctctct ctgcttgttc gatttttgct cttaaatttt cgcaatgctg 5460 tagatggtag ttagcttctt gttcatgtgt tgctaactgc ctttccagaa cagttttata 5520 gtaacctgca agttgctctt ttgtcaatgg gtgctctgaa ataatatcaa gtccactttc 5580 gccaagaggg ttgaattgtc catgctcatt gacatggtaa gtttcaaact tgaacagacc 5640 gttgttagca gattcaatag gtgagagttc agccaactca acagtgaaca ttgtgtgtac 5700 cctatcacca actgtaacaa tgttactacc aatgattctc accattgagc cattgcgagt 5760 gtacttaaaa gttccaaagt cactagccca aagtttcata gttttctcct tagaaaataa 5820 aaaggctccc gaaggagcct atgaagatat tactttgggt atacactgtc aagataaatg 5880 tcagcttcca ttctacgtct gtttttcagg ccgtttgaag tgaccttctt acctttgact 5940 gtaaccttgt tccaccattg catagcttct gcacaaccta ccttattacc atcattgtgg 6000 cgcttgataa atgtagaatc ctgcatagct gtgataccga tgttgtatgt ttcacttaca 6060 agtgcatcga actcgttctg agtagttgga gccttgatag ctttattcac tgctgcaacg 6120 aatttctcaa catctgcgag aagatactgt tcagcttgtt cagccgtgat tttcataccc 6180 atcttaacag gttttccgtc aatacggatt gtaccatacc cgattgttgg gattccggca 6240 gaatctttgt aagcctctaa cttcagacct tcaaagaact taatggcttc taagcctttt 6300 cttgagagtt gcattatgcc tcccctgctg ggttaactgt aactgttgct gcattagatg 6360 tcacagagcc acctgcacca gtaactacac aggtgtagct tcctgaatca gcagttgttg 6420 caccttcttt ggtgtaagtt gcagtagttg catcgaggat gtcttcctca cctttcttcc 6480 attggtaacc tgtcgcacct gttgccacaa cattcagtgt taaggtctca ccttcagtga 6540 tttcttgatt ggctggttgc tgagtaattg ctggtggctt aatagcatct ttcaacttag 6600 cattcagcat tgagaacggc ttaactcttg ccagccattc acagtaaatt gtgtcaacat 6660 ctttaccatt gataattgca tattgtaagt ccatgaagaa gtcagaagtt ctcatttgag 6720 caccaatgct gtaaagcagc tcatcactaa atggaacttt atagtctggt ttgtagtcaa 6780 acttcttaac ttctgcaatg tcagcttcag gccaatacga actataggtg agtggtaaaa 6840 tagactcttg atatgttcta aaatcatatc tcttaccagt ctttacattt gcaatgaagc 6900 ccttcacaaa ctctttgaag tctgggtaag tctttgcttt aatcatttct ttttagcctc 6960 taaatgtgcg tttagtctaa aataaccttt gtggtgtgga gatacatcac caacaacaac 7020 acctttaacc ttataacctt taccaattac atactggata tccataagga atctaccaag 7080 accaacaata tggaacattg gatataatag attctcagag tctggaatat tgatttcagg 7140 tttgtaggtg cgttgttcga ttgttggtgt aatatcttct tcaggccatt tactgagtct 7200 ccatgtcaaa ggtgttggga taacatcatt aaggttgtat ctttcaccat tttgcacgga 7260 attgatatag gattgtagga agcaataaaa gtcttttgca ctcttagctt tcattaaata 7320 tccttataaa tagttaaagg ggcatcagcc cctattcaca cttaagcttt ggtcttaagt 7380 aggttcttaa gttttttaag attcatactc tcatcaaact taaaaccaaa tacattgaca 7440 taatcaatga actcggattt cttactgagt gacaatgcgt aattcatatc aaagttctta 7500 cttgtttctg cgtctggact agagttcaca tcaaatgaga tttctgtagg ctcttgctta 7560 ctttttctca tattatcagt caacaaacat gtatagtttg ctggatagaa gtttacacta 7620 ccatcaacgt agctgtactt attattatgg ataaggttgg aaaatacctt aaggaatgtt 7680 tctgagtcgt ggcaaacaag tttgaattgg ctgctctctc caagtgcaac taatgagtac 7740 ggactttcac tatcgaagtc atagtttgga ttcgatgtcg tcactgttac acgcatcaag 7800 ttattagcaa tagtcttctg tttaaaagaa tttggaacat agtgaagacc tctaccacac 7860 tgattgacta gctctttaag taggtcattt gcatacggtg aattaattga tacagagcca 7920 tcactattgt aattaaaact tactgttaac atttttcagt tctcctgcga tttataattt 7980 tgctgcaata gagaaacgaa gtaaactcac tggaagaaac cattaagtgt tgttcactag 8040 attgagccat tgccctgaaa tacattccag tcaaagcatc atagtgacta ttctttccaa 8100 ttgaggttat atagccatga ctctttgcag tttgatataa atctataata tctgcgattt 8160 ctaattggga actacacata gataatcctc ttgtcttctg taattttgaa agaacaggta 8220 cagaccaatt tcagaggatg aatagtagat taactctacc ctttttgatt ccttacagtg 8280 attggtattc ttacctttct taggtttatt tgattttctc attaagtctc ctttgtagaa 8340 caaggcagac ctacagcttt aagtaagatg gtacagtaat ccatacaaca agtcaagaac 8400 tattgcaagt taaaaaagtt gttgacaagg tacttgacaa ggtgtaggct tataaatact 8460 tagaagataa cttaaaaggt tcctctaaaa aggctattta aacagatatc tttctggata 8520 tctatctttt atcttaaaag ccttttaaga ggtcttataa gaggcatacc aatgaaaaac 8580 agaacaaaca aaggccagtt taaaaaaggc cagtctggaa acccatctgg gagaccaaaa 8640 ggctctcgta acaaaagctc actcgtaaaa gctcaactga ccattgataa ttctgctgag 8700 tttgctgcaa agctgtttga ggcgattgtt acaagggacg ctgctaagct tgcagagttc 8760 ggtttgacga ctgccgatgt aaacctgaag tcgatgatgg aagctggtaa aactatcatg 8820 acccactcag caggtgagat gaaagcgatt gcagcagaca ctaagaagac ccctgataat 8880 ggtggtcagt cacagacaga taacaaacca acgttctctg ctgtagcgac tctcaaaaaa 8940 taattttaaa aggtgttgac agactctaca gagttgctct aaagtctgtc acatcaaaca 9000 acaaatgaga gaagagagta aaatatgagc gaattattta aacatgcgca ccttcatgca 9060 ggtcgaactg aaaatggtgc tgtaaaccat acttcatcaa tgtctgctct tgtggacttt 9120 tacaaagctg ctggttccag ccgtagcaat gtagaaatct taccagacct gttctacaaa 9180 gctttgcgtg aggatgttga tgttgcagtt cgtattttac tgcatatgcg agatgtacga 9240 gaaggtatgg gtgagcgtaa agctttccga actgttttac ttcaagcgat tgaagataaa 9300 gtttagagc ctacacaggt tcttcgcatt atggataaga ttgcagaact tggtcgtttt 9360 gatgacttca aaatcttcgt aggtactcgt tttgagacag atgccttcaa acatttagaa 9420 gcagcattac tagaccctgc aacagcaggt ttagcggcta agtggttacc acgagtaaaa 9480 ccacgccaca aacagtttgt aaaacgtttc tgtaagtttg caaacttaag tgagaaggag 9540 tatcgcacac tgttatctgc actgtctgat acggttgagc aaaaaatctc tgctaatgag 9600 tttggtaaga ttgactacag caagattcct tcactcgctg ctgcacgtta ccaaaagctc 9660 tttaaccgta aagatgggga acgttacaaa gcttacatcg agtccctctc aaaaggtgag 9720 gttaagatta acgctggtgc tgtttaccca tacgatgtga ttaaatctat caagtatggt 9780 aatgcagatg ttgctaatga gcagtggaaa gcactaccaa actggatggc agaaggtgag 9840 aacatcttgt gtatgactga tgtttcaagc tcaatgtctt gggtgaatct tggttcaatc 9900 actgcccttg atattggtgt atcacttgct ttgtatgtag cagaacgcaa cactggttgc 9960 tttaagaatg agttaatggt ttactcaaca aaccctcact tcatcgaact gagtggtgat 10020 ttacgaaacc gtcatcgtca ggtaatgcgt catgttgaat atggttcaac taacttacaa 10080 gcagcttttg accgtattct tgaggtaggt aagcgaaaca acttgactca gaaagatatg 10140 ccaagtaagc ttattatctt ctctgatatg gagttcactc aggttgatgg agctaacggt 10200 cgtacaaact ttgaagcaat tcagagtaag tacaaaaaag ctggatacga aatgccacaa 10260 ctagtattct ggtacttagc aaaccgtaat ggtacttgcg aagtatctgt taaggataat 10320 ggtgtagcga tggtatcagg gttctctcca gccactttaa aagctctgct tggtggtgag 10380 aagtttgacc caatcagcgt aatgctcaaa gcagtaatga ttgaccgtta catctggtaa 10440 aaagttttaa aaagggtatt gacaatgtgt ttgataccct ttaatatgtt ctacatagaa 10500 acgaaatgag agcttttcta agatactgaa aaatatttta aaaaagttct tgacaaccac 10560 taaaaaataa tgttaaagtg gttacataga gtttgaaaag tttatctctg tttagctcag 10620 cttggtagag cgttccgttt ggggcggtaa ggccggaggt tcaagtcctc caacagagac 10680 caaattaatg ttccagtaga caaaatggta aagtcaccac tctttcaaag tggatatttg 10740 agggttcaaa tcccttctgg aacgccagtt ttgacagaag accaattgca gcaaacttaa 10800 tcttattcat ctgacacgaa atcggacaaa gaagagattt ggtctggtca ttaagaattg 10860 cgggtataga gaaagggcgt ctcacatgtc tcattagcat ggtatcggca ggttcgactc 10920 ctgcacccgc ctccaaattt acagaagacc gtttacagca atatttatta aatttttagc 10980 ggaaaaattg aaagatacgg tctggtaata ctaaacatgg ttaggaagca cataaggtat 11040 gtgcggtcgc ctgttaagcg aatggcacag ggttcgaatc cctgactaac cgccaaattt 11100 aaatgtgtcg ttatcccgta gatggtagcg gtggggactg taaatccctt gtcattgaga 11160 ctcggtaggt tcgactccta cacggcacac caaataaagg ttatgtagtt taatctggtt 11220 aaaatactcc cctgtcacgg gagatgatga gggttcaaat cccttcgtaa ccgccaaatt 11280 ataataagta tttcaaaatg atgtttgaga gggctattta gcccctccct taaagagttc 11340 ttacgagtat tctttaaagg agcagaaggc caaattcagc aagttactta aaatttcaag 11400 ccaatttaat tttgaaaaat ttaaaacttg gtctggctca acaattttac agaagaccgt 11460 ttacagcaaa acttaaacaa tctatttctc cggtaaagaa aaggcgaagg ttcgattcct 11520 tcactcggca gatgtcgagt tggtgtaatg gtagcactta agatgataaa caacggtctg 11580 gtaattatct ttgtaggtga gctattaagc ttacctgtga gtatgcgacc acaaagggtg 11640 aaagggtaaa ttctagattt aaacccaaca aggcacatcg ctacagacct taagcaagtc 11700 tgggtagctt atctacaaag ataatttaat ggaagtgtag cagaatggtg atgcggcaga 11760 cttttaatct gacaggcgat gggttcgaat ccctccactt ctaccaatat ggttcagtcg 11820 cagataaggt aatgcagggg tctcataagc cctatgaatg tgggttcgat tcccatctga 11880 acctccaagc tggtatagtt aagaaggtta taacactccc ctgataaggg aacatcggtg 11940 gttcgattcc acctaccagt accaatttca ataaagttgt tgacattgag atgtgactac 12000 tttatagtaa ctgaaaatga ttcagcatat gtataattca aacaccaata catgagcatt 12060 agacgtaatg caatgtgggg aaatttgttg tacatattct gaatagtttt cgttgcgtag 12120 cgtctatttt gcaaatttaa aataaatgca aacgacaatg tttttctggc agtagcttga 12180 taggctaaac accagtgagg tcttccaatc cctcatcaaa gaatttggcg tactagccca 12240 cggtatgatt aataaggtgg gcaacatttt aaagggtatc ccttattggg cttggcttaa 12300 atgcaatgag taccctttaa aatgttaatt acggggcgta tctcagcggt cttctaaacc 12360 gccgttaacc gagtaagtgg agtatgcggg ttcgagtcct gccgcctcga ccaatttagt 12420 tagcagattg cttagacgac cttatcgggt ctccgtgtaa ggaggtggtc tgtatctcat 12480 gttttccaga acatgtaaat aatctgagaa ggggctttac agtgttgtga aaatacggta 12540 agcttcgaat tacaatatgg gacgatgtta agactctaag gcatgagcaa cggcttccaa 12600 caccgtttca aaggggttca actcctccgt cccatgccaa agtcttatta ggggtaggta 12660 gcggctaatg gtagccaaac tgtcttgaaa acagttgcca ctgtagagat acggtgaggg 12720 ttcgactcct ttacttaccg cctaataaga tttacaccgt ccatgcttgc tcgcattttc 12780 ggtttatcca tcgtgtattg tcgtacacac tgataaagca cctagtaggt gtcacggaga 12840 agagataata tcaagctctc caaaggttct agtcaccgga ttaaacaaga ctatgcaaag 12900 acctatttag gtctttttag agggcttcta aggttattac agcttgttgt ggaaccttgt 12960 tgcttaggtt cttagaagtt ctctaaaaag atttaatggg agattgacgg taattggtaa 13020 acctaccatc cttagaagtt ggtgtttgag ggttcgaatc ccttgtctcc taccaaatta 13080 atgcaggtgt agcaaaatgg ttatgcggct gactcttaat cagtaagacg atgggttcaa 13140 ttccctccac ctgtaccaaa cattggggat gtagtttaca tggttaaaac ataagttttg 13200 caaacttaag tacagggttc aattccctgc ttctccacca attagtgcat ccatagttta 13260 aacgggaaaa ttacagtctt ccaaactgag gttgagggtt cgattccctc tggatgctcc 13320 aaattaatgc tcctatcgta taattggcta ttacggttgc cttgtaagca acttatcagg 13380 gttcgaatcc ttgtgggagc accaattcag aggtcaagtg aaagaccgct ggtgtcaact 13440 gaagaccgta acaaattcca cggagttgag ttagcggcac aacttcagac ctcttccata 13500 ctcgcttagt ttatatggta aaacatcacc cttacaagat gaagaaaaag gttcaagtcc 13560 tttagtgagt accatgttcc agtatcccaa ttggcagagg atgcaagctc aaaccttgta 13620 ctagtgacgg ttcgaatccg tcttggaaca ccaattttgc aggattagtt caaatggata 13680 gagcaacagt ctacgaagct gttaataggg gttcgaatcc cttatcctgc gccaagttaa 13740 agaggctatt tagatgagat atttgaagta tgcttcatgg attttcttag ctttgttaga 13800 accatttgca gcaatcttag cagttatctt agcacctttt gtagttccat tctacagtga 13860 gaagaaagga catctacctt tcgggttcag atggatggaa acttatgaca acccaattga 13920 tggcgatgaa ggtcatgtca aaagatgggc taagattaga aagattggta agcttggtat 13980 ctatatgcag agagtcggtt ggctctggag aaacaaagct tataacttct cttaccatgt 14040 gttaggaaga gatgtaaaag atgttactaa gtggaaaggt aatatcaatg taagttctaa 14100 ccctgaagat aatcagacagta gttatctcct aatgtggaac agtaatgctt gggggttatt 14160 cgcttttgta ccatcaatta aaatctttgg taaacaattc tactggagaa tttatgttgg 14220 atggaaactt aaaagtgttg tcccagaaga aagagcattc tcaagggaaa gagttatgtt 14280 ggcattcttt atccatccac taagaaaata aagatttaaa ggggattagt ttacaaggtt 14340 aaaacctcgg tctttgaaat cgaagaagtt ggttcaattc caacatcccc cgccaatgct 14400 ccattactcc aattggcaga gaggccagac ttaaaatctg tgttatgtat cggttcgaat 14460 ccgatatgga gtaccaaatt tagcggtata gcataactgg caatgcagca gtctctgaag 14520 ctgtcttatt aaggttcaaa tccttatgcc gctgccactt ctaaggattc ttacgagagt 14580 ccttaaatgt ggccttatca taaatggtaa tgacccatgc tgtgaacatg gtctatacgg 14640 gttcaaatcc cgtaggtcac cccaatttat agtccaagta gcttatatgg ttaaagcgcg 14700 tgtctgaaaa acatgagaag agggttcaaa tcccactggg ctaccaattt caaaggtgct 14760 taatgaaaga gatgacagaa caaggtaagg agatttttaa tctcttaaaa accggtagag 14820 ggttttctaa tcccttatta ctggtgcagc agttctcggt ggaaccgtag ctgcctctac 14880 atcacttgta agctctatta gctctgtaac agaccctaca ataaaggata aacttgttgc 14940 tgctggactt acaacagttc tgcttaacag ctttacaacg agtctgacaa gcactacatc 15000 aaccactaag acattggcag attacggtca aaagtccatt gatgagtttt catcacgtat 15060 gcaggtagca aaaggatatt ccaatgttat gggtgcagca ggagagcaag tcggttgcac 15120 accatttagt ggtattatgg gtgttgctac agagtacggt caaaaagcta ttgacacaat 15180 taacagtaca ctagatggtg ttaatgatgt attaagtgac ttacaagatg ctattgataa 15240 aggtcttgat actgtttctg atttagctaa tcaagctgtt agtaagatta atgaaggtat 15300 ctcgaagatt acagcttatg cagatgaagt tgtgcagatg attgaagaag aagctgccct 15360 tattgcagag taccttaaaa cgaatatcaa tgggttctta gcaggtatct taccagactg 15420 gtttgatgat gcttgtaaaa ctggtgtaat tgacactatt gcaacaccag aaatgaagaa 15480 cgcattacag aaataatgga agattaaccc taaaaggtaa gggagcagtt tgctaaactg 15540 ccagtagctg agaaatcggt gtaccagttc aagtctggta tcttcctcca atttgaatcc 15600 gtgacagaaa tggctatgta cctgtctgca aaacaggttt ataagggttc gagtcccttc 15660 ggattctcca agttatttta ctctctctca attaaaataa taataatgcc ctgctataag 15720 tattcttcct ttcgctaccg aagagtattt ttagacaggg cttttttaca gagttatact 15780 ttataagaag acttatacag tatgtctctg acgtacattg tggtttctcc ttgacggtct 15840 ctgtaccgtc ttttttaagg agaaacatgg ttaactattt ggagaaaaca taatgagcga 15900 gaccgtttat aaagaacttt atgaagctaa taagaagcta gaatttatgc agaatactat 15960 catggcaatt gcagacagat tatctgtagc aacaggtatt gatattaaag aagcgtctat 16020 ggatgcactt cttgacgctg ttgatgcaaa gttcgaagtt aagaaagaag agactgctac 16080 agactctgaa taattctatt tgcggaggtg cttaatggac ttaaatgctg ttaagcagaa 16140 gcgagtggaa gatgttagga aagtcctagc tggagagttg gggctttctg atgaagtaaa 16200 agaaattatc aaatcattcg gtaaagaccc ctctaaattc cttccaactc aaattctgac 16260 tttattaaga tacacaccag accaagttag acttatcttc aaattgatga ctgataagaa 16320 ctatgtagcc cctcagccgg gttctcaaga ggtcttttta aatactaatg ctgacttggt 16380 tctctatggt ggtgctgcgg gtgctggtaa gactgctgca ttgttgatgg attctttaag 16440 atttattgaa gaccctaact ataatgctgt gtatttccgt cgaaacacga cacagttaca 16500 aggtggttta tggcctgctg caaagaaact atttggtaag tttggtgggg ttcctcacga 16560 gcagaagatg actatcacat tcccttctgg ggccactatc aagtttacct acctagaact 16620 tgaaaagcac gctgaaggtc atcagggtat tgaatactca gctatttact ttgacgaagg 16680 tacgcacttc tctgcttcac agatttcata cctacagact cgtctacgtt ctggggctga 16740 aggtgattca tacatgaaga tttctatgaa cccagacaga gaccatttta tttacgattg 16800 ggtagagcca ttcttagatg aagaaggtta cccagaccct gaaaagtgtg gtcgtattcg 16860 ttggtatgta atgaatgatg gtgttatggt ttctgattgg gagagagaca agattcttga 16920 aatgtttcct cttgagattc ctcaaacata tacattcatc tctggtacga ttgatgataa 16980 cccaattctt gacttcttag aacctaaata tcgtggtaag ttggaaaaca acacccctgt 17040 aaacgttgca agacttcgtt tcggtaactg gaaggctcgt gcagaaggtt caaactattg 17100 gcaaagacaa tggtgtgaaa ttgttgattc acttccagaa gatgtattcg atgtcagagc 17160 atgggactta gcagcaactt taccatctga gattaaccct aatccagact ggacagcagg 17220 tgttaagatg ggtaaatcta aaaaagacgg ttgctattat atcattgatg tagtaagatt 17280 tagagataga ccctctggag tcgaaacaca aattaatttg actgctgaaa gtgacggtaa 17340 gcgaactggt atttttatcc ctcaagaccc aggcgctgct ggtaaatcct acgcaacatc 17400 cctcatcagg aaacttgccg agaaaggtta tcgagcaagg gctaaaccaa caaataaaga 17460 taaagttacc cgatttgcgg ggttttctgc tgcttctgaa gctggacttg taaaagtctt 17520 ggaggtagt tggaacgaag cttacttcca agaacttgaa ggtttttgtg gtgatggtaa 17580 aactaaagat gaccaagtgg atgctaccag tgatgctttc aacagtctta acgaagttaa 17640 attattcaag ccaccatcaa tgggtgctca cacagactta gtgagagga acccatatga 17700 ggggcttaga cgttgatagc taggtgagaa gaatggcaga tattacagaa acacaagaaa 17760 gcttaccacc atttagaatg ggtgaagtag gttctttggg tctgaaggtt aagaatggaa 17820 gaatctatga agaacctcgt caggcactaa ggttccctga aagtattaaa actttccaat 17880 taatgatgcg tgaccctgct gtagcagcat ctgtaaatat tattaagatg tttgtcagaa 17940 aagtcaactg gagattcgta cctccaaagg gaaaagagca agaccctaaa atgcttgaaa 18000 gagcagactt ctttaattct ttaatggatg acatggagca tgattgggca gattttatta 18060 actctgtaat gtcattctgc acttatgggt tctgtgttaa cgaaaaggtt tataagaaac 18120 gtcagggtaa aaaaggaaag tatcagtcaa aatttgatga tggtctaatt gggtgggcta 18180 aattaccaat cagaaaccag tcaacacttg ataagtggta ttttgatgaa gactttagaa 18240 aagttactgg tgtcagacaa aatctaagaa atgtttcaca tattgctgga gcaattaatc 18300 ttggagaaag accactaaca agaaaacttc cacgagctaa attcatgctg tttaagtatg 18360 atgatgagta tggtaaccca gaaggtcgtt caccattact taatgcttat gtaccgtgga 18420 agtataaagt acagattgaa gagtacgaag ctgttggtgt ttcaagagac ttggtaggta 18480 tgccaaagat tggtttacca ccagattatc ttgatgaaaa tgcagagcct gaaaagaaag 18540 ccttcgtaca atactgcaaa actgttgtta atgatatgat tgctaatgac agagcaggtt 18600 taatctggcc tagatatatc gacccagata ctaaagagga tatttttgag ttctcattag 18660 tttctagaca gggtgctaaa gcgtatgaca caggttctat cattgacaga tattctaagc 18720 agattatgat ggcatttatg tcagatgttc ttgctatggg tcagtcaaaa tatggttcat 18780 tctctcttgc agattctaag acaagtctat tagcgatgtc agtagatatt ctgctgaagc 18840 aaattaagaa cgtaattaac cgtgatttag ttgcacagac ttatgctctt aatatgtggg 18900 atgacgaaga acatgtacaa atcacatatg atgatatcga aactccagac cttgaagcaa 18960 ttggttctta tattcagaag actgttgcag taggtgcttt ggaagttgac aaagagctat 19020 ctaacaaact tagagagcat attggtctcc ctcctgctga tgagtctcag ccagtatctg 19080 aaaagctttc tccaaatagc caaagccgct caggagatgg ttataagacc gctggagaag 19140 gtactgcaaa gacaccttca gcgaaagacc caagcacagc aaataaggca aataaataat 19200 ggctgaaatt atctctattt caaatgctac acgagtgcat tcgtataggg gtgtccttat 19260 cattactgat aagctatctg tagaggctgg ctcaagggtc agcctttcag gttatgttag 19320 tgatggtgga gtctctgacg ttttcactat ttgcaggtta cttgatgcac caatgagtgg 19380 aaaaccgttt atttcaggaa attgtagtga aattgttaaa attccatttg acagttcatg 19440 ccttttgggt gtaaagttat ataactgcga gaataaacgt atcaatgtta atagcattga 19500 agccgctttc attaccctcg acactgcatt tcaatcccca atgacagtta acaaagaaac 19560 aaacagactt gaatacattt tttcacaaaa tgattacaaa gtacttgtca aaggtaaagt 19620 atatgatatg attgtaaatg tggtagatga atctggtaac cattcaacag tccttaaaca 19680 aaaagtaagg tttaattaat gggaacatta actattgatg gtaagaataa aatcctcgcc 19740 acgctaaccc caacgactat tattttacac aatgtagacc caacggcaga ccctacagca 19800 aataaggtta ctcagccagt ggctatttat ttttctgaac cggataatgg cttaattgcc 19860 tcagaagaca cagttaatat tactgttcca gcttctgcaa cggtctcaca ctatagcttg 19920 tgggatgcta acgataaatg cgtggcaact ggtgctctta gcaaacctca attctttgct 19980 gaagaaggta tctatgttat ctcttcagtc tctgtagatt taaacaaata gggtgagtaa 20040 aaatgagttc gaatatcttc agacttgctg atagattatt caaccaacct ttactagcca 20100 ctgaatcatt agctcactca gcagcaactt atgtgaataa cagattgctg ggtgatgtcc 20160 aagcagcagt aaactttgat aaacccaaag gtgaagcaag aagtctttta aaagtaaaag 20220 atgacattgc tattattcct attatgggtg gtttaaccca tcgtatgaca ttcattgatg 20280 caatgtgtac aggtggatta agctcttatg aaggtttgcg tagaggcttt gacgaagctt 20340 tagcagatga gtcaattaag actatcgttc tgcatattga ttctggtggt ggtgaagctt 20400 caggttgctt tgaattagca cgtcacatta tggcttcaag aggccaaaag aaaattattg 20460 cttatgtaga tgagttcgct tgttccgctg catatgctct tgcatcttct gctgaagaaa 20520 ttattgcatc accagatgca gatgttggtt ctattggtgt aatcatggtt catcaggaat 20580 taactaaggc atttgaaaag aatggcgtaa caattaacgt catcaaagct ggtgagttta 20640 aaggtatggg ttcaccattc caagcactct cagaagaaag caaagaaaga cttcaaaaga 20700 gaattaatga tacctacgca acctttacagta gttttgtagc tgaatctcgt aatctctctg 20760 aagaagctgt aaagaatact gaggcgaatg tttattctgc tcaggaagct cttgaacttg 20820 gtttaattaa ctcaatcatg tctcaagatg atttcttaaa ttacttacaa ggttctgaag 20880 aggctcctgt aagtttaaac gttaacaatt caggtgaaga aatgactgaa caagaaaagc 20940 aagaactaga agctttgcgt cttcaggttg ctcaaatgaa agctaaagaa caggaagctg 21000 ctttgtcaga tttgactaat aagatttctg cttctgctga agcttttgga tttgatgcaa 21060 aagaagctgc aacgactatt ttaggtgctg gtcttgataa ccctctgagt gttctgttta 21120 tgaatgctat ggaaggtgct aaccagaaac ttaatgaaac tatcgcatcc catgcttctg 21180 caatggaaga aaaagaatca gaaattacca agctgaaaga aactgctggt gctgttcttg 21240 aacattccaa cgctatggaa gaagtgggta atgacggcga agctgatttg gttgaagaag 21300 aaaaagaacc agctaagaat gcttccgaag acaccgctga acaacgcaaa ctggctctcc 21360 agaatgctct aaaatctctt atcaaataag gaacacaaca atggcatatc aaggttttac 21420 taagttaggt aaaagagaac ctctgaatga tatcattctt tgggaacagg ttaccccaac 21480 aggccactct cgtaaagagt acaccccaca ggcatctaca gaatatcgtg taggtgaagt 21540 tctgaaagca gacggtacta aggttacagc agggcaagaa gctcaggctg actctgtatg 21600 tatcgttaac ttctacgcag actcacaact gtcttatcat ggtcagttga aagttgttgg 21660 tatttaccgc gacgcagaac tgaaagacat gcttactctt gaagcaagcg ttgacgctgc 21720 cgaagtcaag aaagctctgg ctgccaaagg tattgatttc gtaccaactg gcctgtaata 21780 aaaataataa gacattctgg agaattttac aatgttgact aattctgaaa aaagcagatt 21840 tttccttgct gacctgactg gtgaagtcca gtctatccca aatacttatg ggtatatttc 21900 caacttaggt ctgttccgtt cagcaccaat cacccaaact actttcctga tggatttgac 21960 tgattgggat gttagcttgc ttgatgcggt agaccgtgat agccgtaaag cagagactag 22020 cgcacctgag cgtgttcgtc aaatcagctt cccaatgatg tacttcaaag aagttgaaag 22080 catcactcct gatgaaattc agggtgtacg tcagccaggc actgcaaacg aactgactac 22140 tgaagctgta gtacgtgcta agaagctgat gaagattcgt accaagttcg atattactcg 22200 tgagttcctg tttatgcaag ctctgaaggg taaagttgtc gatgctcgtg gtactctgta 22260 cgctgacctg tacaagcagt tcgacgttga gaagaagact gtttacttcg accttgccaa 22320 ccctaatgct gacatcgacg cttctatcga agaactgcgt atgcacatgg aagatgaagc 22380 taagactggc actgtaatca acggtgaaga aattcacgta gtcgttgacc gtgtattctt 22440 cagcaaactg gttaagcacc ctaagattcg tgacgcttat cttgcacagc agactccgct 22500 ggcttggcaa cagattactg gttctctgag aactggtggt actgacggcg ttcaggctca 22560 tatgaacacc ttctactacg gtggtgttaa gtttgtccag tacaacggta agttcaaaga 22620 caagcgtggt aaggttcaca ctctggttgg cattgatggt gtagcagcaa ctgttggtgt 22680 tggtcatgcc ttccctaacg tatctatgct gggtgaagct aacaacatct tcgaagtggc 22740 atatggccca tgtcctaaga tgggttatgc aaatacactt ggtcaggaac tgtacgtatt 22800 tgaatacgaa aaagaccgtg acgaaggtat tgacttcgaa gctcactctt acatgctgcc 22860 atactgcact cgtcctcagt tgctggtaga tgttcgcgct gacgctcaag gtggctaata 22920 aacttaggag ggttatgaat gtgttataca ggcgacccag ccaataaccc tcttgataga 22980 gtaagaatcc tctgcacaga cactaataat gatgaaattc ttattgagca gtctgtgcta 23040 gagtggttct atcaagaatc tggaaaggat gaaaagaaag cagccatcaa agctcttaaa 23100 tatttactct ttcaagtagc caagatggga gatgagaagg ttggtggtgt ttacttacgt 23160 aactcttcca gattcaaatc tctgaaagct gtttatgacg accttgttaa aagctctgtt 23220 tcaggactac cctatgcagg tggtattaac cagtgcgaca ttgatatgcg tcgtcagaat 23280 ccttgctctg tcaagaaata cacagaatat ggtgatgctg ccagatacga aggcagagat 23340 tactgcaacc gtgttaatgg cgtatttatt atcgagcgag atgaataatg gttaaaaggg 23400 ttattcaccc cgctagagca aaattagtcg gggctatgaa gaacttgcaa acggctaatg 23460 ctcaagttgg gtattttcaa gaacaaggtc aacatagctc tggtttttct tatcctgctt 23520 taatgtattt acaagaagtt attggggttc cttcagcttc tggtaaagta tatcgtaggt 23580 tgtttgaaat cactatgatg ctaaacaaac agaccttgtt agagcagact aagaagaatc 23640 tatataagca acttagcagt ctcaacacag acccttcaaa taccttagaa gcatttgcaa 23700 agaatgctca aaaggcaatt aaaagaggtt ttggtaattc tgctatcctc cctcctaacg 23760 caccttccac agtcaagaaa aaaggcttta atgcacctct tgttgagaca ggtgacttaa 23820 gagatagcct tgcttataaa atttctacta agaagggtat taagaaatga gactcttaaa 23880 cagacacagc tttatagtaa agcgtaaagt ctctgaagac ggttattata atgatgatgg 23940 tgattgggta gcttcacaag atattgtaga ggttaactgc aaaggtaata tccagccata 24000 tatcaaaggt tctgtaaaga atggtacaca gattgcttta ccggaaggta ttaggcttac 24060 cgatacaaga atcctgtata ccacatataa acttagaact tcagatgatg tagagtggaa 24120 tgagtctgac attgttatga ttgatggtca tgagtatgaa gtatttatga ctatggattg 24180 gtcacagcaa ttagcccata cgtcccatta tgaatatatc attattagaa gggataaaat 24240 gaatgcagtt agaaacagca gaacttgaaa aaggtctagt tagaacctta gtggatgtta 24300 ttggtcacag actaactcgt gataaaaata atagaccaaa tgtaattaga gcttaccctt 24360 ctgataactc aaatgacaaa ggtttaaaac ctgaccagcc atttattacc gtatattgtc 24420 aagatgctgc aacaccttat ggttgggttc ttgataagtt tgttgaggat gatgtagttt 24480 gctacagaat tgcttttcag attcctgtac taattacggt gaatggtaaa ggtgctcaca 24540 gtattatgct tgagcttaaa caacgattag agatgagttc agtcagggat ttaattcttg 24600 aagaaacagg ggcaacagtc ttagacactg gagctatccc gaatgactat acttatctta 24660 atacagattt cgaaaattct gcgcctcttg ttgtaactct tgtaaaaaat tcagtcctga 24720 aagatgaacg tggaggtatt attgaacgtg tcattgttga tggtgaatta gtttacgaag 24780 aaggacaaga gccaccagaa tatactatcc atctagatgt agactccaaa ggggtaaaat 24840 aaatgtggaa tccaattgtt aatgtagata ttacattgaa caccgcagga actacaagag 24900 aaggttttgg gctaccacta tttttagctt caacagataa ctttgaagaa agagtccgtg 24960 gttacacttc cttaactgaa gttgctgaag atttcgatga aaactctgct gcatataagg 25020 ctgctaaaca actttggagt cagactccta aagtaaccca gctttatatt ggtagacgtg 25080 ctatgcagta cactgtatca attcctgact ctgttactga aagtaccgat tattctttga 25140 ctgtagctgt gagcggtgga atctctcagc cattccagta tacttcaaag acatcagata 25200 ctgctgagaa ggtgttacaa cagcttaaaa cacagattga agctgaccca acaattaaag 25260 ataaggtcac tgtgaatgta actggtgctg gcggttcagc cacaatggta atcaccaaag 25320 ctggtgtgaa cgacttcgtg aaggttactt ctacagcaca aacagtgtca attgcaagta 25380 caactgctga cacagcatct actgctttgg cagctattga agcttattca actgactggt 25440 atttcattgc agcagaagac agaactcaac agtttgtctt agcaatggct tctgagattc 25500 aagctcgtaa gaagattttc tttacagcta actctgatgt aacagcactg caaggtacag 25560 aattagctag tgcaaatgat gttccagcac agcttgctaa gagtcagtac actcgtaccg 25620 tttgcttgtg gcatcacacg gcagcagaag actatccaga aatggcatac attgcttatg 25680 gtgctccata tgatgcaggt tcgattgctt ggggcaatgc acagctaact ggtgtagctg 25740 cttctctaca gccagctaat aagagacctc tgacaagtat tcagaagtca gctttagatg 25800 cacgtcactg taactttatt gaccttgatg gtggtgttcc agtggttcgt agagggatta 25860 cttctggtgg ggaatggatt gatatcatcc gtggtgttga ctggttagaa tcagacctga 25920 aaacttctct gagagacttg ctaattaacc agaagggtgg taagattact tatgatgata 25980 ctggtattac ccgtattcgt caagtcattg aaacctctct gcaaagagca gtcaacagaa 26040 acttcctgtc atcttacaca gttaatgttc ctaaagcctc tcaagttgct ttagcagaca 26100 agaaagctcg tatcctgaaa gatgttacct tctcaggtat cttagcaggg gctatcttgg 26160 atgttgactt gaaaggtaca gtggcttacg aataatagag gtaaattgga atggctatgt 26220 atcagcaata ttcccctaaa gacgttgtat gtagctggaa cggcattgct attgaaggct 26280 ttgctccaga ttcattctta cgtctacaga gaacatcacc acttatcaca ccagttgtag 26340 gtgcgggtgg tcaagttgct ctgacaagaa atgcagacaa gacaggtact attgagattg 26400 agctaatgca gacttctctc tctaatcaga tgctttctgc aattcaagct aaacaagaca 26460 atatggaact tgaagaagat atctcttcta acttcgtaat ctacgaccca tcaggctctg 26520 ttctggcaac tggtattaat gcttggttgc aggaattacc gcaggttgaa cttggtcgtg 26580 accagaactc taaaacttgg atttttggtt gtgagaagct agactacact tctacaattc 26640 cagcgtcaag tgtttaataa atcctataag ggggagactt taaaaggtct tccccttttt 26700 tgtttctttt aaaagtatta aggaatcaca atgaaaacag aatctagagt aattaatggt 26760 aagaaagtaa atatcattct gcttggggca agagatggta ttaagatgtc tatgaagttg 26820 ggtaaaattg ttgttccaac ctttgcacag atgctatcaa gtctgactga taaagataag 26880 aaagaagctc caatggttcc atttaaagaa cttgttgaag cttgttttga cagaattgaa 26940 gaaattaacc ttgaagaaat ggctaacttg ttatttcaag gggcaactgt tgatgacttc 27000 ccacttaata ttgatacgta cttccaagca aactacggtg agtttattga ttacttagca 27060 tttgcgctgg aggcaaactt cggaagtttt ttcgaagcaa gcattttcaa aagcctaact 27120 tctcagtaaa catgggtaac actctacaga caccactaac tgatgctgct gtagaggcaa 27180 cctatgaaga agcagacgag atgaaatttg tgcttgctat ttatggtatg gaagggtgta 27240 aagaaacact tgaccaactc tttgctatga cattctctga tttattatca ttgagacaat 27300 ttcttgaaat tcagaggtcg tataaagagg aaattgctta caacgaactt agaagagcag 27360 gaaaaatgta atggcacaat atacagttga tagcttcatt gtggaacttg gtttcagtga 27420 aaaggtaatt aaaggcttgc aaagagttga gaagatgtct atgcaagccg ctcagcgtat 27480 tgagcgaaat atgaataaag cctttgatgt gaagcctaat aaaagttctc aggaagcact 27540 taatagaatt gtaaaaaatg ctcagtctgc ttcgggcaga atcaataaag cactcaacag 27600 ttccttgaac cttgattcac aaggtgtgaa atctcttaag aaacttgaaa ctcaagcaaa 27660 aaagactgca aagggtatta acaagtcctt aagagatgct atgaaggttg acggtaaaat 27720 cactattaag acaggtagag ggagaggtgg acgaaatatc cctcctgttg gtggtggagc 27780 acccagaggt ccgagagtag atgttgctca gagacaaatg gaaagaatgt ttaacaacaa 27840 cttctattca gggttaactc gtagactgga aacaattggt ggtcaaggta accagatggc 27900 agcttctttc agaggaagct tacaaagtat ctataataaa tacaagggta ctggtaaggt 27960 tggtgagtat gagatggaag ttaaaaagct catcgacgta accaaacgtt gggttattgc 28020 agaaaatgct agactaaaat cagttaaaga agcagcttgg ctacaggaca gagctaactc 28080 atcactacgt caattagttg gtggatttgt ttcagcttat gctttactgg aactatcaca 28140 aaagactatt gaggcgggtg taaaaagaca atctgcacaa ttagcctcta cagctatctt 28200 tggagcagat acccagcaag ccagaatgtt tgctgcatca ttcgcacacc agattggtca 28260 gaactataca gataccatga agcagtactc aaactttgct gctggtgctc aaccaacgct 28320 aggttttcaa ggtactcaag agttctataa gaacgctgca atgtttgccc gtatcagagg 28380 tgctaccgat gaagacttga aaggtatcat ggttgcattc cagcagatgg catcaaaagg 28440 taaagttcag gctgaagagc ttcgtggaca gttaggtgac cgtttagcag gtgctgtgca 28500 gctattcgct gatagccattg ggaagactcc acaagaactt gataagatga tgcaagacgg 28560 taaacttctt gctcaagacg ttctgcctaa agtgtctgaa agaatggctg agcttgtcaa 28620 acaagcaggt ggtatgaacg ccgtatctaa gcagactgct acgtcaatgg gtcaagctaa 28680 ggcaatgtgg gataacacac ttgtagcact gtttaacaat tctagtgagg gtatttcacaca 28740 gttatctaac tctgttgcaa tgttcttaca aggttctatg gggtctacag aagctttagg 28800 tgttgtgatt ggtaacctgt taaaaggtgc tagtaaccta cttgactttg ttacagactt 28860 catgtacaga gtctctgcac tatactacta tgcaagagct tggtataaag accttgacag 28920 tagtcagcaa aaactagtca aaagtgctgg tgaatttctg ggaacagtca ctatgattgg 28980 tggtgctgta gcaacggtag ctaaaatggc aaagcttatc actggattct ttgatacagc 29040 aattgtgaga aaaatccttc agaggcttgg tattgaggtt gcagaaaaag cagcaccacg 29100 agcagcacca ttacttgcat ctccagttgg tgttgcagca gcaacgcttg cgctatctaa 29160 gtcttctgac cctaatgctg gaaagagatt caatgaagct aatatcacta atcctttcaa 29220 tgaagctgtt gcaaatatta caaacccaaa aagaccaatg ttctttgatg agaatggtca 29280 acttaagttt gcacagtaca ctcaagatat ggaaggtaac agaaagctaa ttgacaatgg 29340 tctatctaat tgggatattc tcatggagaa gttatcagca tctcttgata attttgccaa 29400 taagtttaat cagacaccaa tgatgatgac accttctggt ttacctatgc agactaaaca 29460 aaccctgaat gttactttca aacttgatgg taaacaaatt gctactaaga tggtggatat 29520 tactgacaag aatcaagaag acattcttct aagttcaagc tatccagagg aagaataatg 29580 ttatgggatt ctaatatgca aatcaaatat agtggcaaag atggcatcta tttccactta 29640 agagataatg tagatgcctt cttaacctta tcagcaactg aaaacatgga atttgacagc 29700 cctatgcagg taactacaca gaacatgcaa tcagggcaaa ccgtcacaga taatgttcaa 29760 agagcaccca gaacaatcac tattagtggt gtcgttgtag ttggctatga aggaagctta 29820 ttattaactc gtcagggtca attagtagaa aacttcatcg acactctgga aaactggcgt 29880 gaccagaagc agattatttc ggttatctgt aaagacggaa tcaagattga tgattccatt 29940 attacgagct ttaaagcctc taaagatgtt ggtatttcaa atggtctaag aatccaacta 30000 acctttcagg aaattaactt caaagctgtt gtggggcaaa ctgatatctc tgctgcaact 30060 ggaaaggccg ctactacgaa tgatggtggt gcaacttcta agaagaatac tggcaacact 30120 acgacaagtt taggcaatgg taaattaaac tgccagttat tatttgacct aaacgccaat 30180 ggtgtaaggg aacttactag tgctgaagat aaggctcttg gaaaatgttc aatgtctgca 30240 aagacaagaa aaggtgttac cacatttagt gacgaggctg aaaaaaatgc cggagcagcg 30300 ttaaatagga ctgctggaac tggaaaggca ttacaaaagc actcagtgaa tccgaataag 30360 aaggagactt attaatgtca caatatattc ctgttcctga tacagaatgg tctacacaaa 30420 ctgtaactct ggatggcact gtctttgtaa ttgagctaaa gtataaagaa aggcttgaca 30480 gatggttctt gacgctatct gatgttgatg gtaatgtatt attacatgaa aagaaatgcc 30540 ttgcagacca atcaatcaca ggacgctatg taattccttc attagctgga gagctttttg 30600 ttgaacgaat gtacggtact gatttacaac ctaccagaaa taacttcgga agagaaaagg 30660 catttgagct taattattac actcaagaag atatgagatt aatggagaac ttataatgtc 30720 tgtaaaagat agcactgctg gggcttcttt taggtgctat caattggctg taggtagtga 30780 aactacagcc tttaatgata aacctacaag ccatgctaaa gattctatgc aaatggacta 30840 tttcgacaac ttacaattca cttgtaatgt gtcttatacg tctcagaaaa ataaagtaac 30900 ctctgacgat accacttttg aaatctacaa ccttaataaa gagatgagag ccaaattcaa 30960 aaccgttggt gcaacagtta tgctcagagc aggttatacc actggtttta aaagggactc 31020 aaacggtgac cttattattg aatatgacaa cctcccatta atttatctag gcactattga 31080 gtatgcttat acctataagc gtggtgttga tatgattacg aaggttatct gttccaatga 31140 taaaatggaa agaaccacga ttaagacatc aatttcttat aaagcaggga caacacgtaa 31200 aagtgtgatt agagatttag ttagcagatt aggcttctca cttattgatg aagacctttc 31260 aagtattgat ggttacactt acaagaatgg ttttagtgtt tgggggagtg ttgcagaggc 31320 acttacaaag gtttgtgaag aaagtagtct acgttggtat acatttaaca agcaaatccg 31380 agtagtccct tttaatgcta aagctagaca actttcttgg gaaatttacc catataacgt 31440 tattgactct ttgcaaggtt actacagaag aactagaaag gttctgaaaa aagagaataa 31500 gacagttatt aaagttaaga ctggagttcg ttgcaaaatc catttagatg ggagaattaa 31560 gatgggtgat aacatcacta tcagagaaag tgaagatttt gaaggtcagt atcgagtaaa 31620 aggtctttct cataatcttg actttactgg tggtgcttgg acaactgaac tagatttaga 31680 gaaggtggaa taatgaagtc accagttact agaatgtctg ggtatgtttc agaatgtctt 31740 gatgaattta gaaaagaact gtatactgga ttaccagcta ttatccagtc ttttgattca 31800 aagactcaaa cagccactgt taagccactt tactctatta acggtttgcc tatgccagag 31860 attactggtg tacctgttca attcccaagt ggtggtggag catctttaac attccccgta 31920 aaaactaatg acagatgctg gttagctttc tcaatgttac ctttagatga cttcgttgtc 31980 aatgacaaga atgttcagat ggaaacaaac atgagaagga cgcacgatat ttcagactgt 32040 gtagctttcg taggcatctg cacaagaaca cagaatttta aaccagaccc aacagcagtc 32100 agactccatt ttggtgactc tgtattaaga atcactgatg atggtaattt ctactttgaa 32160 ggtgatgtac acatttctaa aaacttatat gtaacagaag aagtacatgg ttcagatttt 32220 atcagtgaca cgactggtgt gagctttaat gaacacacgc accattatta ctggacagac 32280 cctgctggtg aggctgatac tacagaggca caataatgaa aacagacttt gcattaaatc 32340 taggtggtga ctatgttgcc actttaggtt cagattcagt gtatgtggct catggtgatt 32400 taaagattac tggtaaccaa attagaatta tcccagagga tgataaagct actcaggttg 32460 ctcaaagact tcatattaga tgccttctaa gggctggtga agtcttcttt aatacatctg 32520 ctgggttccc atatttacaa cttgccaaat ttaaacagaa aacttctatc tttgataatt 32580 atatgaaagc ctaccttgtt gaaacaagag atgtatctaa catctataac tattcttctt 32640 caatggacaa tgctcaaaga aaagtgactg ttaattttga tgcaaccact acaacagata 32700 ttttaacaga cattacgcaa gaggttaata tctaatggca ggactaacta caacaggatt 32760 acaaactcta agatatcagg agatttttga taatatcaaa tcaagacttc ttagagatat 32820 ttcaccaaac cttgacgttt ctgaagacag tcaattagga ctcttcctag cttcaattgc 32880 aaggtcttta gcagatactc atgagattct atcagaagtc tatgacggtg gaacaattga 32940 caaggccgag ggttttaacc ttgacgatat tacagctttg aacgctgtct acagatatgt 33000 tgctcaggca acaagaggtc aagttgagtt tactgggact actggtgcta ccattccttc 33060 aacaacaaga ttaagaagta ctgccggaaa catcttttat ccagttaata acatcaccct 33120 tactccatca tattgtgttg aagctacact tgaagttaac tctttacgaa ctgatgcaga 33180 ttatgttatt attattgata acgtcatttt ctcatataaa ccaacctcat tagacacaat 33240 caccacgctg ctaacaaaat tagcagaagc tattaatggt ggtattgtag caaaagcaga 33300 agtcattaat gatggagccg cattaagagt ctataaagac gaaggtgata tcattgcaag 33360 aacaaaccct atggttgtca ctgcaacaac gtttctgacc tttacaaaga ttacaactat 33420 ttcagatgta gtagctgaag aggtgggtgc tacccctgct ttggctggta cgcttattga 33480 gattgagaca actgttgatg gtcttgacag tatttataac agatatgact taacaactgg 33540 tagaaacgaa gaaactgaca cagaacttag acagagatat ttagagtcct tagcagttac 33600 tggtgtgggt actttggatg caattgtagc tgctgttaaa agagttcaag gtgtctcaga 33660 tgcttcaggt gttgaaaatg atactgaaga gacaaactca gaaggtcttc caccaaaatc 33720 ttttaagatt gtcgtagttg gtggtcaaaa tgataatgtt gctcaggcaa tctgggatac 33780 aaaacctgct ggtattaggg cttatggctc aatttttggt acagcccatg atttaggtgg 33840 tttggcacat aatatttatt ttagcagacc aacaccaaaa tacgcatttg ttaaggtgtc 33900 ttactcacta tacgacgaag aaaacttaac aatccctgaa gaggatatca gagacagcat 33960 tgtacaaggt attaatgcct acggaagaac tgtaaggtt ggtaatgacg ttatccctaa 34020 cagaatctat ggacatatct atgacgtaat taaaggtatt gagattaatg aagttaaagt 34080 ggcattatca aataaccaat cagttccacc tagtgacggg cagtatacta cagcaagaat 34140 tactgttgac ggtgaccaat atactgtttg ggaaagtagc cagtatacca tcactaagga 34200 gtaataatgt ttgaaaagat tgatagtgtt tattataaaa cacttgatga aaggactgta 34260 acacagttta aagataaatt tatctataca agtctcttga aagcaatcac tgatgagcta 34320 caaacactag aggatgtttg ctggcagatg cacacagaga gaaatatcag gacgtcagta 34380 ggtcaacaac ttgataatat tggctcactg attaaagttc ctagaccttt aggtgctgat 34440 gatgaaacat acagagctat gctttatatc caaatcttcc taagacgttc tgatactact 34500 ccaacattct tgcaaaaagc aattatgaca ttgtatggtg caactttctc tcagattttt 34560 gagcatatta ctcctaagac tggtggtatc gttatccgta ttaatactag aaaaagcgtt 34620 cttgatgctg catatacact gtcaaagatt tctgcaacaa ccactggttc cgctgttatc 34680 ttaagagatg ttactttaaa tgggactgct tggacacctg tagaggttgc tgattcatca 34740 cttgctattg ttgatgataa agagaactgg tttgtaactg atgctaacag gggtctggta 34800 acaaataaca ctggtggctc tctggagtcc aacctagtag ggagtcttgc agatgctggt 34860 gttattgatg gttactttaa ggttgacaga acagcaaacc cacagagcga tgattatatg 34920 actgtagata ggtccaataa tagtggctat ttcattgctg gtaaagaagc tattgcaggt 34980 ggtgcatatg gaatcatggc tgaggttgca caaattgtca aaggcagaaa agataaatca 35040 caacaagaag gaaattctta atggcagttc taaattggtc tacaaacgaa gtagatactg 35100 atggtaatca gttaaaagtt ttaccaccac cggaagttca agagacaggt cttttaaagg 35160 gtgagcctat gggtagacag tggttcaact atattatcaa ctacctgctg aataaagtaa 35220 atggcactgt tggtgaagtt cgttcatatg caactgagca accagattta gtggctaatg 35280 gctggaatct cattaagtct gagacaggga ctgcatcaac aagtacaaga aacctttaca 35340 catatgaata tgtaggagct taataatggc agtaggtgaa attcaaatta gtgccttgcc 35400 acaagcggcc ttaccagttg atttgagtga tatcttccac cttaagcaag gtgttgagga 35460 taaaagatgt acgcttgagc agttgttagc acctcacgca tctttgagga ataaccctca 35520 tggtgtaact aaatcacaag taggtcttga taatgttatt aactctcttc aattagttgc 35580 agctaataac ttgtcagata ttgtaagtgt tgctgaggca agagcaaatc tacaaattat 35640 gtcgtcagag gaagtgaata acttaattca gcaacatatt gacgacaaaa gtaacccaca 35700 caatacaacg aaagcacagg ttggtttaag taatgttcag aactggacaa catctaatct 35760 gtacaatgaa gatgctgata agtatgctac cgcgaaagca gttaataatt tatacaaagc 35820 tatccaagcg tcatatccag tagggactat tcatctatct gttaactctg ctaacccatc 35880 cacttacttg ctttgtggag gtacttggga gttagtttct aaaggtagag cactagttgg 35940 ttatgataca gattctagac ctgttggttc aacgtttggt tctcagactg tagcattaac 36000 aaataataat ttaccagcac atactcactc tatctatcta acaggtggtg gtcatacaca 36060 ctctgcaagt gtatctatct ctagttttga ttatggttca aaaagtacat caacttttga 36120 ttacggtaca aaaacgacta atagtgctgg tgctcacact cacacgttta gtggcacaac 36180 aagtaatgct ggtaaccaca accatagagt ccctatgagg ggtaatgata ggggtggcac 36240 aaacgctatc actgcatctg ctgatgctgg tgttggtaat gctatgtata ctgatttagc 36300 tggtgctcac acccatagct tctcaggtac aactgcatca tctggtgctc atagccatac 36360 tgtcgcaatt ggtgctcaca gccacactgt taatattggt tcgcacagtc atacaggcac 36420 tgttactgtt tctagctctg agcatacaca ctcagggaca tctggttctg ttggtggtgg 36480 tcaagctttc agtgttgagc agccatcttt tgtagtgtat gtgtggcaga gaacagctta 36540 atttctttac aggggctata aagccccttt taagaggaa attcataatg gcagattaca 36600 aattgagtca attaaactca atcgacacaa ttcgttcaga agacctattg cacatcagag 36660 ttaagaaaag acctgaaatg ttgggtgacg aagaccgtag aatgacctat caagacttct 36720 tagcttcctt caaactagaa aggtttgttc agattgctgg gagtactatg gttggggatt 36780 taggtattgt caagttactt tacggtggta aggcagtatt tgacccaaca ggctcttctg 36840 agattactat tggggatatt ttaaagactt ttaaaattaa ctcaaatggg cttaaactca 36900 ctattgcaga tgccacaagg tcggcaactg tttatcatac tttgaataaa ccaagcccta 36960 atgaacttgg tatgagaact aatgaagaga atgatgcaag atatgcaagg cttgctgtta 37020 caaacacatt ctctggaact cagaacattc aaggtgatgc taacttactt cgtcttagaa 37080 accagaatgc aaataatgcg caatatattg agggtgtgaa cttagatggt tcagctagat 37140 ggtgggttgg tattggtagt aatggctctg atgaagtaaa actgtacaat aacaaataca 37200 actcagcttt gactattgca agcaatatct ctgttaataa gtctttagca atcactggac 37260 aagttcaacc ttcagatttc tctaacttag atgctagata cttcactcag acagttgcta 37320 atcagagatt tgcacagtta gctggcaata atacttttac aggtgctaac acatttagga 37380 ctatgagtgt tatttcaaat gctgctgcta tcacactgca atgtgcatca gcaaacgaat 37440 ccctgtatct acttgcaaaa gattatgaag gtggaaactt atggtatctt ggtaaaggta 37500 gttcaggtgc tggtgtaact atctacaact ataccactga cacctctttg gtcttagatg 37560 ctgctggagt atcagcaaat aaaaatgtca gaatcactgg acaagttcaa ccttcagatt 37620 gggctaacat tgactctaga tatattccgg cagcaacatt aagtacaatt gcaagaacta 37680 atgcaaggaa tacttttaat ggtgtacaga cagttgttac ggataatgaa ggtctgattg 37740 ttaaaaactc tactcagaat agaccattat atattcgtgg tgtggacact actaatgtat 37800 caagatggtg gattggtgtt ggtggtgctg atacgaatga tgttacccta aataacagtt 37860 attctggaac ccaattggtt ctcggaaata caacatcata cattaacaaa acattgacta 37920 ttgctggaca agttcaacct tcagatttct ctaacttaga tgctagatac tttacgcaaa 37980 gtgctagtga tagcagatac ctaagaatca gaagtactag ttttaattta ggaaacggtg 38040 aaaagtgggc taaaatcgct actgttgtaa tgccacaatc aacatctacg gcagtcattg 38100 aggtttttgg aggtgctggt tttaatgcga ataacccata ccaagcaggt aagtgtgaaa 38160 ttgttttacg aacgtcaaat aataatacaa aggatttaaa tgctgtagct tggagaacag 38220 cagataatgc cctcatcacg gatattggtt atattaacac ttctggtgac acttatgata 38280 tttactgtaa ggttggtggc taccaaaatt ctacggtatc tagggttcaa tcttctagta 38340 atgcaagtgt acagttgttt gaagtcccgc aaacatttga tgatgctcca caaggtattg 38400 tgaagggtac acttgcaagg tactacacaa gtttgcaaaa accaacccct tcagatattg 38460 gtgcatacac taaagcagag actgaccaga aaattgcaga agcgattagt gactctacag 38520 acctgaataa aatctatcca gtaggtattg tgacgtggtt taacagcaat gttaacccta 38580 atacagcact tcctgggtta acttggacgt acctgaacaa tggtgttggc agaactatta 38640 gaattgcagc agcaaatggt tcagatgttg ctacaactgg tggttcagat tctgtaacgt 38700 tatctgttgg taacttacct tcacacacgc acagtttctc tgctaccact tcgacgtttg 38760 attatggcac taagcacaca gatggtcagg gtgctcacga ccatgataga ggtaatatgg 38820 aaattcatgg tgattttggt ttcttcagga gtgacacatc aagcttctac actgctagtg 38880 ggtcttttgc tatctcaggt tcacaagcat ctagaggata cacaggtaat aacttcactt 38940 acggtactcc tgttaatttc tatgcctcta gaacttggac aggtagaaca agttgggtag 39000 gtgctcatac acatggtgta ggtattggtg ctcataacca tacggtaagt ggtaacactg 39060 gtggtacagg ttctggttca gcatttagtg ttactaacca gttctacaag ttaatggctt 39120 gggtaagaac tgcttaatcc cttattgact gattgttaag atggtgttaa tattctttat 39180 gggtattctc accatcttgg ctgatgaggt gattaaatgc ctacaatcct agcaattctt 39240 ctaaaaaatc taggtagctt cttctggaaa ctcattttat cccttctaag tgaatacatg 39300 attgagaaag tgttctttag gcttgcaaga taccttgcga gtaaaacaga cacacctatt 39360 gatgatgagt tcgtagataa cttagagaaa gcttttaagg gggagaataa atgaagtggc 39420 tagaggaagc ttttaaaaat aatattggtg caattgtagt tggtattttt agtgttattg 39480 ggatgtatac cacgatgcaa gtttcaagtg gtaaacaaga agtgtctgtc tcaacaaagt 39540 tacagcagct agataattat tcaaaaagta attactcagc tattcgtgat ttacagtctg 39600 acatgagact gctacagcta gggatggaga accagaaagt ccagttagag aatgttaagg 39660 gtgagaacgc aaaacttact aagactcttg ataaattctc tgatagtgtg aacaatctgg 39720 ctcaatcagt atcagccctc caagctatta ctgaaaagaa cacaaagaat actgaaaagt 39780 aaagtttaag gctccttttt acgggagcct tttttgtttt atttacctac tgacaaaggt 39840 gcttcaatct ttcctgcatg ttggtaattg ttaataccac caataaagtc acttgcagtg 39900 agatgtttta agtcacttaa agtgttaagt gggataccaa tctcaaaagt tggtgcatgg 39960 aactcttcat tgttcatcag ttcataaacc tgtttcatat ggttctgata aatctgagta 40020 tctccaaaga cacctatcaa gtaccgtgga gtatatccag tcatcttaca aagaacttcc 40080 agaataaaac cgtaagatgc aatattaaat ggaagtccta aaaaggtgtc tactgaacgc 40140 tgataccatt gtaagtcaac ttcaccctcg ttagtaatat aaatctgaaa cagaacatga 40200 caaggtgcta gagccattga gtttgctgca atatctgccg cattccaagc attaacaagc 40260 atgtaacggt ctgtgatatc acccttcatc ttcgttacta aggtctctaa ctggtctaca 40320 acacaaccgt tatgaccttc aaagtttctc cactgaacac cataaattct tccacccgca 40380 tcttctaacc aatcttgttc agaagagtaa ttagagctta accagcgttt aaaatcatct 40440 gaccagatag tccagcgttc tccatcattc tcaccccaag tacggtaacg gagttcaccc 40500 agcttattct caccattcag gaaccataaa gcttccccga taacttgccg tgtaaacacc 40560 tgtttagatg ttaagagcgg gaaaccagtt cgcatatcaa aacgaaactg aggtggagca 40620 aatgcagaga taacatctcc agttcgtgta gtacgcagtt caccaactga taaaacatgg 40680 ttcaggatat ttttgtaact caaatctgct tgtgacatat caaaagtgtc cttttacttg 40740 tggaacataa atttcaaaag ttgctttacc atcctctgat ggttttgact gtacctttgt 40800 aaatacacgg ttatcataca gcttctcaaa gaagttttca aaaggtaaat gcacagtggc 40860 ctcttcagta actttatgga aaactgtatg aaacactaca tcagcatacg gtaaagcatt 40920 gacaaggaca cctgcaccac caattacaaa gacatcttca tcaatagagc tatcaagata 40980 cttcaaaaat gctccaaatg actctttact ggctttagca tacattacct catctttacc 41040 aaagtctatg cctaagtatg gtacagagtt tgttaagatt aggtttgcac gttctggtaa 41100 aggtttacta cccagagtct taaaagtctc attccccatc actactaagt tatttttagt 41160 gagtctctta aactcttgca tatcctgttt atgtcgaggc cacggcatac cagttggagt 41220 accaaactca ccattttcac cacttgcaaa gattaattta atcattttgt aaaccctttc 41280 ttaatgaacc agttgataac attcttcaca gctttattgc tatggtagat taggtgtggt 41340 gtaggctggt atgaaccata ggcccagaat gatagatgct caccacaacc aacacatgta 41400 gtactttctt cagctatatg accattaaca atcacatgaa cttcaccttg caagtctgta 41460 cacccacaat gtgggcaacg gataggtgtt ccatcagact catagcagtg ttcaattttc 41520 atttatttaa cctcaaaaac tggctcaaga accaatataa agtctacaca atcatcttct 41580 tcatccagaa taccatcaaa gttcttagga acgaagtcga agaggctcat aacaaaacag 41640 tcagaagtaa ccctgatagt tcctcccatg ttctctacag tcaacactgt acgactttct 41700 tttacctctc tcagaagatt actcacaaag tcatctaaga agtacttcat cagtgactta 41760 aaacctttag ggtaatctgt accagagtat gtttcaatct ggggtacaag cttaacattt 41820 atactagtct ttgttaagaa cgtgctagag aacatgctat caggtaactt acaaacaatc 41880 tttccagtac cttcatgctc aatctcaaca aaaccagctt cgtcgccaca tgtaactatt 41940 ttaaaagatg cttcattctc atgctgtgaa gccataaact ttttaagcat cactttaagg 42000 aaatctgcat gagcatcttg taagtagata tcaatcatag ttaatcacct attatgggaa 42060 cagacacttg atgtcatcat ttttgaaaac aaaacttgtg tagttgtgac catcaacatc 42120 cagccaaaca gcctgaacat ctacaccatc aagattgtgg taaagctctt tgatgaagtg 42180 gtctttcaca acctgactac tagttgtttc cagcttaatg tttgagattg ctgaacctac 42240 agccatataa cccatgacac gtttcttctc agtatgctta atcttaccat ctttgtaagc 42300 cataatgaga ttggaaagaa tcttcacacc ataatacttt tcaaggtgag taggtacacc 42360 gtaaaaacct aatgcgaagt tttcagagtg gataatgttt tcacgtttca tattaatctg 42420 ccaaccttaa attaaaatta acaccaaatt tttcacatac ttccaacata aactcaagag 42480 agacattacc agtgaggttg attatgttgg atacacgagc ttgagagata ccacaaatct 42540 tagcaacttg ctcttgagaa agacctctgg atttaatctc tctcttaaaa cgatgtgcaa 42600 cgaagtctct catttcgtct acatccattg gacaaatata actctccatt tcagcttctc 42660 tgtcagcctc ccaatcatct tgtggagcat aagggtcaaa aacctcattc atctttcttc 42720 ttccgtttac gtgaagcatc aatcaatgaa tctatgtttg tagctctaac cttttcacgt 42780 tcatcgttaa gataatcatc aagagccttc tcaatctgtg aatcatcttg acagataact 42840 gtaaagactg taaagccatc tatatcatca attatcttac cataaccgct tctgggatgt 42900 aactttttaa gagccatatc aaatacctgt gcagcttctg ttttctaaga aatactcaac 42960 accatacata gctttttgca tcaagtcttc tttaaactga atacgatgat tgagcatagc 43020 ctgtacatca atatcttcat ggtgcttctc tttaatgttt gcagattgca ggaaatactc 43080 tgcaagaaca cgatactgat agtcagttac cttatcagtc atctctgtta aagactcttc 43140 agagattggt ttaagtaact caccattagc caaagcaaca cctttaacaa tctgacaagt 43200 gtcttctgga acacctgata agtccacatt tgggagttct gttgcattga ctggtaaatt 43260 cattgacata accattgcag cagctaataa aatctttttc ataatgacct caaagttata 43320 ttaaattttg tattacattg agtataaaaa taagctataa cacctgattt gtcaacagat 43380 tttatagctt atttggcaga ttttttttat aaggctactg ccatccttcc ataccaaacc 43440 ataccagaca tagccatacc cgaccgtacc tcgcctcaca acacttaaaa atcctcttag 43500 aagactctta agtgatgtaa tcgaatttta atgtagctcc gattaactac ccatacctca 43560 cctcatccaa ccataccatg ccttaccaga ccgcacctta ccttattaaa agaccctatt 43620 taaagacctt ttaaaaaggt gagtctcatt ttaaatgtag ctgagactaa ctacccatac 43680 tgtaccgcac ctgacccgac ctgaccagac ctaacattac cgtgccacac cgtaccgaac 43740 agaacattgc catacctcgc atcacttaaa aaccctttta aaagactctt aagtgatgct 43800 ggtgagtacc cgtcggttta tgctgctcag tatactcacc aaattttcta tgtcaacaac 43860 ttttattcat aatccctaat aactagtccg acagggaact gtaaagaacc cttacgagtc 43920 atcttctgga actgtaccgt taaaggcttc ccgataaact cttcaggatg ctcagcaaga 43980 tactgtttct tctcatgagt agtcttccat gagacatcta caaagacgtt aggaagagtc 44040 tctacaacga acttgccatg accacgctta tcagtcttta caccagtcac tttaaactct 44100 tcagtgtgca tcttcttgtg cttaatcaag aagtatgaac ggtgacaaca ctcatagaag 44160 gagtcttcag agattgaacg gtacattgca ccttcaaact tagcttcaac ccacttatca 44220 tgagcttcat caaactcttc ccaagaattt acacgacgag acttaacagg aacaacttta 44280 cagccgtctc tgaagtcatt caatggtgaa gtctcaataa tatctctacg ctcaggccac 44340 gtcttagtac tatcacagat atcgtaccag taaaacttga gcaagtgtct gtcaggattg 44400 tcttcatttt taatcatgga gacgatatct tctaagtccc acccatgagc ataaatctct 44460 ccatcaaatt catcaacatc tttgtggagc cttagcattg ccataatgtc aggtattagt 44520 tcggcaggga ttttataaac agtattttca cgagaatatg ctgtaaatac actgccaata 44580 cttaagtgtc ttgaaattct acaacggaca ccatcaagtt ttggttgagc atcagcaggg 44640 aacttcagat actttgcatg actaaccttt gcagcatcat gagcaagctg cacacctacc 44700 ttctcagtat tctgtgcaga ctcttttgtg taagcatagc ctttgcggtc aacctgcttt 44760 ttatacttag cagcaacttc aaagagagct tgctgttcag cgttacgctc attcttttta 44820 ccgatgtttt taggttctgc tgtatactct tcaaacatca tcttgccatt ttctttgcca 44880 tacgtggtaa caactttgtc acctacagcg acacatgacc agacgttaaa agagccatct 44940 ttattttgtt tgtacagtat tgtcatttta ttcctctgag tgataccaag tattgcaagc 45000 attacatgcg taaagctcta agtcattttt atctggttta tgaaaacagt ttgctccgca 45060 gtggcaacga aacggctttc caccaactgt caggatgaag gattgaacct ttccatcagg 45120 agtccgtaca gcatttttat gcttgtcttc tttattcatt tgtgctattg cctttgtcag 45180 atttcatata ggacatgtta ctatgccttt taataaaatg tacaacgcat tttggtgtat 45240 cttttgtgtc tttgatgtgc aatctatcga aactgtgtac tgtgaaggtt gcatctgtca 45300 ttgtctgctt aggtttcatt ttcttttacc accaatctct acgtcaataa cttgaacatc 45360 accagcaaca tcaaacttat gaatgatgct ttccacagtg taagtccaac cctcaatgcg 45420 aaccaactca ccttctcgtg ggacgattgg gttacgttga gctacggttg tagtggagtg 45480 aacaacatca taacagtaga tatagtttac taggacttcc atatcttcac cttaaaagaa 45540 taagtcagat gcttttgggt tgattaaact catgcagttt tgaagcatgg cttcattgta 45600 cccatcttgg caaactacgt agagtttatc gaaagtttct tttgatgctg ggtagactga 45660 taactcctgg catacactaa gataccatta gtaatctaag cctctgctcc aagcgtcagc 45720 gattagggct gtagctttgt ctttgcttct gataacttca tcagactttt caattttact 45780 gttcacgatg ttctacctct ctgtacgttc gtcgatagta tatgataagc tgtgctaact 45840 cgttgctttt aacatctgaa cgtagcagtt gccaatcaaa acctttaccg actcttccat 45900 ataagctaaa taattttact ttgcgtttca ttttggtact cccaatactc agaggccaat 45960 actaatacgt tcacccttga ggactcctgt acggtctctt gcaatcttgc cgtcaacaat 46020 aaggatatgc gcagacctta aagattcact attaaaacct tttacgaact tgctaggcat 46080 cactacaatg tacatcttct gaatcaactc tggagtgtag cagttatcat gaagttgctg 46140 aataacgtct gcaagtgtca tttttgatgt ctccaatatt caatatctac aagttcttgt 46200 gcaatgcttt tcagattacc tttcaagaaa accttctcag aacctgaaag agatgaattg 46260 tcaattaacc tgttcatcct ctcaaacaac ttctgtttac ggttcttgat agtttccttt 46320 gaagcacctt tcatcatcgc tgcatgggtt cttccacggt ggctcataag ccctcctata 46380 taagatattg tataaggtac tcttccctga gcaccttgtc aacttagttt tgcaaactct 46440 ccgtggagtt tcacagcagc ttcacagtaa gctttatggg cttcttcagg tgtgtcatgg 46500 tgacctaaaa acatcttctt acctttataa cttatctgtg cgacccactt accagacttc 46560 ttcttaaggc ttacaccctt gtacccagat ttattggtgg ctagtttacc tttattccaa 46620 gcactttgga agtcatctgc ttcccttaag tttgcaatcc tgttgtcaag agagtctccg 46680 ttgatatggt caatgatacc ttttggcatc ttgccatata cataaagcca tgcgagtctg 46740 tgtgctttat gtgctttctt gtcaaaatag atactaatct gtttatgacc agttgaatca 46800 gtctggatat tacctgccac ctttcctgca taattactgt taaaaacact aacagctctt 46860 gatttacctt ctctacgaag ccaagtaaag acccctgttt cggggtcata gtgcagcagc 46920 tcctttaaac gtttttgtaa aattaaatcc attaatcaat gtacctccaa ccagctctta 46980 ccaacctttg ctgtaccagt tacaagtgtt tctttcctca aacctaagtt ttttgaagct 47040 tgtccataca tccagtcagc aattgctttc atatcctgtg tcataccctc tggacattcc 47100 caactatttt catcgtgata tgccagaagt aaccttgctc cgatagctgg ttttcgagca 47160 ttcagttttg tcaggccatc ttcacaggct tttcttgctg ctaggttgat agcctcattc 47220 tgaatctgtg cttccgaact catcaggagg tagttcagta gtttatgtgg agatttgcac 47280 catatccatg ctccagcgac cctgatataa ccacctttag caattgaaga attcttccca 47340 aaaacctctt ccagagcctt tttagacgcc ttaaaatcgg cttctaagct atcaagtaac 47400 ttcttaatct ttggcagacg catatagtaa gtttgtttag tcaatgcacc ctcttccgta 47460 gatgatgcct tgatagtttt tgcaaacttc tcgtctccgg ctccaaataa cagggcgtag 47520 atgccatttt tgctcttctt acgacctttt gtaatctcgt gaagaagttc ctcatcctgt 47580 gtctccctgc aacgaacaat atcctcttct ttgttaagac caaagtaaat actgttcagt 47640 gtatgcgcat cagtccctgt gtagacttca tagaggtcat tttcagcatc ataacgcaga 47700 tacttgtcag tttctgggtt aagatacttg tcaagatgtt tacagtagta tctaccatca 47760 tcttgcttag tgaactccac tgactcttta ccctcagtta ccgctttagt gaagtcttca 47820 tcacccataa agttacaaag gagaactagc tgggctgagt tttggtcaac agaaacaatg 47880 ttagtcccct cttcacaaat ccacactgcc ctcataggtg ctccgtagac agcagcacca 47940 gacggtacgt ttacaatacc atactgtgtc atacgtccag ttgaagtacc aaacaccatt 48000 gcaccagcac taaggcgacc atcaggacga atctggttca accaaccttt ttcatcatcc 48060 tttgagttct caatagttct gcgtcggtgc atcaaagtat agtactttgc aatcttctgt 48120 ccaagttcac cttcaatcgt atcataagat gactcagtaa gctttggtga agtacggatt 48180 aagcaaggct caagcaaatc tgtgtacttc ttcacagacc agttatgctc aatgtactgt 48240 ataccttcat gttcaacata actcaaacca caccgctcaa ccatttcctg ccacttagga 48300 tgttttgtaa tcatcttttt attgtctttg aaacgacaaa ctttgacagg gcgaccgtct 48360 gagtctttct tgtagttcca gtcatctgga atccaaccaa ctgatttcaa gtagtcttta 48420 acaacggcta cctgagtcat acgagaaact tcaaactcaa ttggtgtata tggtgcatca 48480 atcaaacctg tgtagcgact tgactcaagt tcaaagtggt taacaacgtg actgttatag 48540 tacttcacag tcttgactgt ttttactggt ttccagtctt tgcatttctt accaatcttt 48600 gcgttcaact cattgcaaat tgcacgagca tccttcattg ctacaaaacc ttccttgtac 48660 tcttcaccag ttacagtgtt ggttggtgta tagcaatttc tcttttcaat gttaaaaatc 48720 tttgtagttg gcttaccaaa tggtttaatt tcgtatgtct gcatctcacc attacgtacc 48780 tgctgacgat actttgtctt agggtacttg gtaattctct tcagtccatc tgcatgacca 48840 aatgtttcaa catactcatt ccaagctttt gcaaactctt ctccagtgac tttacctttg 48900 gtcttaatag ttggaggcag gtgtggttca acctctgaag caagctcatt agtcaacttg 48960 tcaagttcct ttacatggaa ctccataagc tctttatcag ctttccagcc attgatagct 49020 tgttgactca tccagaaaga tgtttcttta gctcgcatat aggtttcata agtgtctatg 49080 ccacacttct ttagcttcag atattcatta tccagtgcgc gtttagtttt ggcgttaata 49140 cggatatctt ctacaacacg agtgaagatt tctgcattcc acacacccca atgttcaatc 49200 tctggtttac ggacaccaac acgagcaccc catgcagcca aaccatgagc acctttataa 49260 ccctttggag ttggtctatc catccactga acacgagact ggataagaga atcctgaaag 49320 aaattactcc acggcttgca ctttggatta tcaaagttcc ataaatcagg tgcaatgtga 49380 ttgaaaaccc accagtcata acccagacca ttatggatgc aaagtcgttt tgcctttaac 49440 gcaaactcaa taccttcacg taagccaccc ttgatgtact tggtatactt gtgaccgagg 49500 ataggttcat ctgtaaagac ccatacaggt ggctcttcat cgtcagattt atagtctgcg 49560 aaagccatta cgtgcacttt agtgaactca aggagtaaac catcagtttc tgtatcacca 49620 accaaatgta agtttttaaa atctacgttt tccattttta ctccctctaa aatcattaac 49680 ctcatacatt actgcaaaaa attataaaaa gcaagttgac aatgcacttg acaaggtgtt 49740 aatctttgcg aagtgggttt ttacttaaaa ggttacttaa cagtttaaat atacagatac 49800 tttaaaactc ttaaaagatt atttaatagc ttttaaaaag ctttaaagta taacgtatag 49860 aatacgttaa gataaaagat taaaacttaa tagttactta aaagaggctt acatgcagaa 49920 aatgtttgtt cacccagaca tagctgactt tgttagagct ttgcagaagt tggaagaact 49980 tgacattgct gctcaacggg aatatgctca ccatcacagg agaatggttg atatacaaca 50040 tgaaatagag ttgtctgaaa actatgaaga tgacttaaaa tgctctgtat ttgagcatat 50100 gaaagatgtt gctacagcga gacgtaaagc taaagacaca gttgctttac tagattctct 50160 taaaaagagg ttgcaaagtg gtacagacct gtgtaatcta gcatcactga ttaacgatgt 50220 tgaaacttct tgggataggc actattatcc acgttctgaa aagacacttg acttttcttc 50280 atccgaaaac ttaaaatgtt ctagaaagaa actcaaccaa ctgagagaga aataatatga 50340 atatcaatgt agaaaagatg cttgaagaaa aaggtattga cgaagcgttc ttaatcaatg 50400 ccgtagaaag catggctatg attcttcgtg gcaacaacta cacagaacag tttatgcctg 50460 caagctataa cttgcctaaa gataagtctg ataacggtgc ttttgcagaa caggttaata 50520 tgatgctgtg tgataaaaca cttgctttag catctatcgt tgtaggtgtt gatgctcttg 50580 cagagttcat tttttatgag atgcagaaaa atgactatat tgccatgacc tctgaagaaa 50640 aagactcgct actgctctta ggttatgatg agctagttaa cctgttaatt tcgtcaacga 50700 gtgctgttat ggctgctctt gagaagcgaa tggaagagaa gctgtcacga tatgaaaagc 50760 ttgattgggg tgtagaagag ttaaacccac gaatcaaaga gattatccag caaaccaaag 50820 attctttgga agaagctgtg aaaaatgatt ctgtagctga catagagcca cttcaggtga 50880 aagttgcatt gatgattcca gccatctcca cgatgatgaa tatcgttgca ctaatccagc 50940 tttcacagat gatgggcaca agcattgagt tcattgagag tatgactggt ggtgtgagta 51000 tgcaagcaat caatgatgtt ctggtgagca ttggtgcttc aatcattgaa gagaagctgc 51060 gcattaactt tggtgatgat tttgtgaagc aaatctcagc tatggctgaa aaagagtatt 51120 cacaggctaa tactgaccaa ctgcactaag tctttataaa ttttacaagc ctccttagtt 51180 gggggctttt tagtaattaa gggagataaa atgagtaata ttatcgcatt tactggaaag 51240 gcacgttctg gaaaagacac ctcatgttct attgtgaaga atatcttaga ggatgagtac 51300 ggctacaatg ttgcagtaat ggcctatgca gacaacctta aactctctgc ttcaaagata 51360 tttgacctga cttggaatga cctgtacggt gaaactaaag agactccaca ggtttttgat 51420 ttatcatact ctgaacttat gcctaaagtt acggaggcta tcgagttcac cttcagagat 51480 gaacgttatc atatggactt taagcttatg tcagagttaa ccggacgatt agtcatggag 51540 cttaagaagg tcgctaaacc gactctattg acacgtctag ggtttagtaa aaagtataaa 51600 ttctcatcaa ggcaaattca acagatttgg ggtactgaag tcatccgtaa agttatgggt 51660 gacaaattct gggctaaaga ccttgaaaaa cgaatggctc gcttctttga atcttgttca 51720 cttatgaatc aagagggtgt tgttttaatc agtgacttaa ggtttgactc tgaagcggag 51780 tggctgagta gatttgcaca ccagactatt gaagtaaaaa gagacaatgt ggataaggtt 51840 tcatcacatg tttcagaaaa tgggatttct accaaatatg cgcgtgacat tatccataat 51900 aatggtactc ttgcagacct tgaaagtaag ctaagagcta tccttaaaat ttaaaagaga 51960 gcatgaagat gagagtaaaa gataatttca aagttattga ccatcgttta gtggaactct 52020 catctctttc caatgaggta atgattgaac gtcttaagag agttgaatca cgaaggaaag 52080 agattgcaga tgaaatccat gaactggaca agattgaaaa tggattgaag gcagaactac 52140 aacgaagagg tgctaatgtc taaaggtcgt aaattgaaag aggctggtca gtttgttggt 52200 cattgtgcat gtccacgttg tggttcatca gatgctggtt caatctacca ccatgacgat 52260 gattcttatt cgatgacttg ctttagctgt aacaaaggtt tcccagagtg ggattttgat 52320 aaaggacaga ttgtgagcac ttattctact ggttcagata ataaaaaccg tactttccgt 52380 gggatggatt tagacgatgt aaaagaaaac cttgaagcaa tggacttgaa agacaggaag 52440 attcctgcaa aagttcttga acgcttaggt atcaaggtcg acattgacag tgatggtgaa 52500 attgatgcac atttctatcc gacttacaaa cgtaatgaag atggcaagct agaacatgtt 52560 ggctaccgtg ttcgtcaccg ttacccagaa gaccatccaa aagaacacct acgtggtaag 52620 ttaaaagact tttcaggtgg tgttggagac attaaaggtg aactggcaat gttcggttca 52680 tggattgctc cagaaggtgg caaccgtcta ttcatctggg aaggtgagat ggagtgtgct 52740 acagcaatct acatgacttc tctggcaatt aaagacaagt ctcgtcgtaa gaactactgt 52800 cacgtatctg ttccatcagg tgcaaacatt aagtctatca aagacaacta tcagtacatt 52860 acatcatttg atgagattta cttgtgcttt gataacgatg aagcaggtgc taaagcaaca 52920 aaagaggctg ctggcatcct acctattgag aaggttcgtt tattccagta tccagaaggt 52980 gtaaaagacc ttaatgaatg gtggacaaag ttctataaag agaaagacac agttctggaa 53040 ggatttaagc agcgtatcta caatgcacct cgttattgcc ctgctggtat caagaacttt 53100 gcagatggtt ttgaggcaat gaagaatcgt ggtcagattc cattgattcc tttcccagaa 53160 tttttcgggg atttgaacag actaacttac ggtggttatg gtttaggaga gattacaact 53220 ctggcagcac catcttcagt aggtaaatca gcttacactc gtgagatgat ttattcagct 53280 tggaaggaaa ccgattacaa tattggtgta attccggtag aagatactta cgaagaactt 53340 atggaaatgc tctgtgcaat ccacctgagc aagcagattt ctgagattcc ttatgatgaa 53400 cgtgattggg atgaactaaa gagagcacac gcagaactat ctaaaggtcg tcgtatccat 53460 atcgttgacc atcaaggggc aattgaccaa gataacctgc tggaatttgt tgactatctt 53520 gttaatagtt tagactgtaa gattatcatt cttgacccta ttacgttggc tctgtcacgt 53580 tcagatactg atgaagagga agttttgtct gagctattgc gtcgttgcaa acgctaccag 53640 tatgcacagg taaacgtctg tcacgttcgt aagagtgcag gtggtcagaa ggctaactct 53700 gaaggtgggg atatctctga agaggatatt aaaggttctg gtgcgtattt ccagatttct 53760 atgaacaaca tcctgttaat gcgtaacaag gttgacccag accctgttaa gaaaaacttg 53820 acaaaaatca agctaactaa atgtcgtcgg catggtaagt caacgggtat tgctggtcat 53880 acttggtaca atccagatac aggacgcctc atcaaagcat ctggttgtgg agttgacatt 53940 gatggtgcag cagaaaatat tcgccaacag tttggtattg gtgaagtgga agaccattac 54000 gggactctt tgccacatta tgaggatgaa gtgtttgacc gtgagactgg tgaagtctat 54060 actgaagagc agcgtcaaag ctcaacaatt ccacctgtat taagtgagga tgcagatgac 54120 tgcccattcg aaactgagtg atagttataa aagagagggg ttcataccct tctttgaaga 54180 aaaaagttta aataaatttc aggaagagtg tttgacaaag attgataggt tctatagaat 54240 gctcctcatg aaatgtgatg gggaggttgc tataaaagaa gattcctacc aaagcacgat 54300 tacagtcatc attacactgc ctcagcataa tattagttgg ctgtttataa ttaaagaaaa 54360 tgtgtttgaa tatcaagtat atcggagaat accatgaaac actctaaagc atttgaaaaa 54420 gtttttgggg attccttaaa agccactgct ggaaaaccag caaaatacta tgaagaaaaa 54480 cgtgtaagaa ctggaaaaac tgcacgtaaa gcagcttcta aagataagca caacttccag 54540 taattagtat ttgacaatag agtatcaaca aactagaatt ggtactcttc ataaattgag 54600 atagaggttt aaataatgtc taaagttgtt aaaatgaaag ctccggtaga gaaatacaat 54660 ggtactgaac gccaaactct gcgatacctg ctgaaagatg tctggtttta ttacctgaac 54720 acttcaccac gtccgggaaa aggtaagtct attgataaga aattcccagg caaagactgt 54780 aactacagcg tatcaattct ggcagaagac ggtaacaagc tgtttaaaga atttactaag 54840 tctaagaaaa acccagaagg ttgggataaa gttactactg aagcagttga tgcagatgac 54900 ttcgaagaga agtttggttg caaaccacca tttgaagcag atacttacta catcttgaaa 54960 gtaagtcgtg cagcagctta taaagatggt gctgtatgga cagctaaaca gtcattccct 55020 gtaatgctga ttgaagaagt aaatggtaag cgtgtagctg ttaagcagcc gatgaagaaa 55080 atcaaagctc aagcatctga taaacatgaa gatgacaaga actatgatgt aattcatcca 55140 gatattgcag ttggtaacgg ttcttttggt agcgtgattc tttctactca cttctacact 55200 tttgagaaca atgttctgac aaaacctatt caggaacagt ttatcattga tactcttgta 55260 ccttacactg gtggtaacgg tgctaacgga gaacctgaac tggatgaaga cgaactggct 55320 atgcttggtc ttgatggtgt cgaagataac ggtgaaatca ctgaagaaga cgcaacagac 55380 cataaatctt cgaatgattc tgatgatggt gatgatgaag atttgccaga cccagatgac 55440 gaagaagatg aagacttcga tacagaagat taatctctaa agttacttta aagccctgta 55500 ctccgtatgg ggctttttca tatggagagc cataatggag aagtacacat taacaaaact 55560 tcccgattca gttacacatg tttttattga ctctgacagt attgcctata aaggtgcttg 55620 tgtagttgag aaagcaaagt ataaatatgt caataaactc acagcagaag agtctgagcc 55680 atttgataat gcgaaagatg ctgcaagatg gttagcagac cagagaatcc ttgtggaaga 55740 gcttggcctg acatttgatg aagatgaatg ggaaagacag acttggaaag aagctaagag 55800 tgaaaaagaa gctatcatgg ctactcaaca ggtgcttcag gaatggctta aggttgttgg 55860 taaagagaga acttgggtag gttacttaac agagaaaggt gtgcataaac acaaagacat 55920 taaaggtctt gagcaccaat atcaaggtaa ccgcaaagat gctgtcacac caacacactt 55980 agttgcttgt cgtgagtatc ttctgtcaag accagagttc aagctgattc ttgatggatt 56040 tgaagctgac tctatcgtaa ttgctaaagc tgaaaagatg ggtaaaaagg ctgccttaat 56100 gagtattgat aaagaccttc gacaagctga aggtacttac tgcattgaca tgacctatga 56160 aaaatcacct ttaattttta ttgctgataa caatgttggt gaaatctggg attgtccaat 56220 aaaatcgaca ccaaaagcta agaagacagt tggggtaggt tttaaatttc tttgttacca 56280 agctgtggct ggtgataatg ctgataatta ttttggttta aagggcgttg gtaaggctac 56340 tgtaatgaaa gcccttgaag ggaaaacaac ttacaaagag tgtcttgatg ctatctatga 56400 actttatgct aagaaagagt catacactta tgtctcgtgg gatggtcaaa caattaccag 56460 aacaccttta gagttaatgc agcaacactt tttcttagct tatcaggaaa gaaacaagaa 56520 agatgatttc acttttaaga aatataattg ggagccttgt atgaatgaag attaaaggat 56580 ttggtaattg ccccacctat ggtcattggg tatctttatg tggggaagtt gaccccacta 56640 aacattttgg ttttgtctat ttagtacact gtaagaaaac cggacaatat tatataggaa 56700 ggaaacagtt taacagtgtt accaaaagaa aagttgctgg aaagactcgg aagaaggtag 56760 tcactaagga gagtgattgg atgacttatg agacttcttc tgagtatatt aaaaaagata 56820 ttgagagctt tggaaaagaa ttttttgact tttacatcat tcaaacctac tacacaaaag 56880 gtggcctagt ctatggtgaa gcaaaccttc aacataaatt cgatgtaatg acaaaaagga 56940 ttgactcgaa gctcagactc ttctacaatg ccaatattgc agcaattaag tttattacta 57000 aagaaactta tgaagatgct gaaaaaagaa tccataaggt aatgaaagca aattgtgctt 57060 gataactatt gagagagaat aaaatgttta acaaaagtaa agctgtgagc catgtagcaa 57120 aagttgacag caagattgaa gaacttgagc gcattcttgc aaatgccaga gagtcaataa 57180 ttaaagaagt tgaagctgtt gaatctcaaa tgcagcacct aatgcttaaa cgtcaagagt 57240 tacgtgagca tctggaatat attgaaacac gagagctaaa agttaacaga tttttaagga 57300 gccaaaatgt ttaactcaag agagtcagta aaaaactgga accttcgttg tggaaacact 57360 caaaagcaac cttacagtga tgagtattgg gaatctttaa aatctcaatc tctgtgtatg 57420 cttgaagaag caaaagagct tgtaaaagca attgaagaga aagaccccat tgagacactg 57480 gatgctcagg cagatttgca atatgttctt gatggcttga tttatctgtc acaacatgac 57540 cataatggcg ctatgaaagc tgtttgccat aataatgacc tgaagtacac agacgactat 57600 gaagaagctt taaaacgtct tgcagatatt gagaagcgta ctggtcaaga gtgtatcatc 57660 agaatgtcag tagttgatgg taaagaatgg tatgcaattg ttcgtgcagc cgatgggaag 57720 attatgaagc aatctaatct ccctaaagtt cagcttggtg aatacattgt agaacttgaa 57780 agccaagaac tttttgtggt agtatctgac acatgcgtta tctgcaaagg tattgtatgt 57840 agcttaaagg atttgggtgt agatggtttt gtagaagtta atccaattac ctctaaagca 57900 gataaagatt tctgtaaaga gaatggacta tggattgcag atattgtcta ctatgatggt 57960 gagcagttcc atgtaacctc atacccgaaa ctgaattatg atgctaataa cctgaagtgc 58020 tggttaaaag gggttggtta taatggattc acagaacatt aataaagaag gtgtggctca 58080 gaagagccac ttctcaaact acaatatttc tatgacggtg tttatgaatg acccgttact 58140 tgagaagtat ggtgagactc cagatacact tctggataat gaacaagttt taaaagcagt 58200 cctgtacaaa tacgggattg atattgagaa agagtattct tttgaaatct gtcaacacag 58260 gaatactttt ggtaaagttg taatggctcc actcttcatg ggtgtagaaa ggactgacta 58320 tggttggtta tatctaaaaa gaaacttgga gaaataccgt gtctaaagca aaaaagttat 58380 cttatgatga cattatctca ggtgctaaat taggtgttga tagtatcgga caagatgtta 58440 agcacggaga cacagttatg tactgtgacg accgaagagg cagaagtcca atcttgtttg 58500 gaagagttgt ttgcaagatg cgaggtaatt atgttgtttc agatatggat gtcaacgtcg 58560 cacaaaagct caaaacaatc atggatagca agatttcatc atggctctta aattgtatgc 58620 acgcatcgtc aatcacaaag gtaagtgata agttttacga tatgtggcag aatgagcaaa 58680 ttttcaagat ttaaactagg gagcctcttc ggaggctctt ttcatctgta ggatttaaaa 58740 atgattaaga caattaaaaa atcaaacggt acagtagtaa gctttgaccc agaaagactg 58800 aataaatggg catcatgggc agataagcgt ggaattatct ggtcagaagt cactatggaa 58860 gctatgaaac gtgtctatga aggttgcacc acaaaagaga tgcaccaagc catgattgat 58920 gtttgtgttg ataagcaaac tcaagagtac tcagatatgg ctggacggct acttctggga 58980 attatctaca aagaagcctt tggaggtttt actaaggttc ctacgctggt taccttcgtt 59040 aaaaatatgg agagagcagg actttgggag aagatggatt attcacagga agagcttgaa 59100 tacctgcaag gttacatcgt gcactcaaaa gatatctctt acggttatgc agtcttgaaa 59160 cagttcagag acaagtatgg tatccgtgat attaaaactg gaaggctttt tgagtcacct 59220 caatttatgt ttatgggtat ggctatgaaa gcctttgaga agcaaccaaa gcaccgtaga 59280 ctgcaagatg ttatcaagct gtacacttac ctatctgacc tgaagattaa cgctcctacg 59340 ccttatttaa acggtttaag agcaactaaa tcaggctatg cgtcatgctg tttgattaag 59400 gcaaatgata ctgctgaatc acttggtatt gctgcaaagg ttgcttatga catgactaca 59460 aagcaagctg gtattggtat gttgatggag actcgcacta ttggtgatgg tatccgtcaa 59520 aatactattg agcacatggg taagctacct tattacaagc ttgtacgttc atctgtagag 59580 gcaaacaaac agaagagtcg tggtggttca gctaataact tctacactgc tctagacccg 59640 cagattgaag atttactgcg tttgaagcac cctacaacgg ttccttctaa acgtattaat 59700 gagatggact actcattcgg tacaaacgat tatttctggc agtgtgttca gtatgataca 59760 gattggttgc tattctctta caaagatgca ccaaaactct atgacatgtt ctacacagca 59820 tctgctgatg agtttgctat ggcagttggt catgcagtac attcaggtgt taaacacaga 59880 cgagtcaagg ctcgtgaaat tgctaagctg tttattcaac agcgttatgc tacaggtcgt 59940 gtgtatccat tcttcactaa caatgcaaac acacatacac catttaaaga gcctttgaag 60000 atgtcaaatc tttgcatgga aattgtgttg ccagtgtacg gctttgagaa agagacagac 60060 ctttacagag acgatgctgt gaaggaggat ggtgaggtag ctctttgctt cctagctagt 60120 ttggttgcag ggagaatttc agaagatgaa tacgctgacg ttgcttatta tgctcttgca 60180 atggttgact ccgttattga ccttatggat tatccgtatc cgtcgatgcg taaccatgtt 60240 cgaagcgtc gctctgttgg cattggcctt acaaatgtgg ctcattacct tgcgaagaac 60300 tacgtgaact actcttcacg agcaggtaaa acgaaacttc atgaacttgc agagatgcac 60360 tcttactatc tgcatgaagc ctctctgaga cttgctaaag agcgtggcgt tccagagtac 60420 atgaagttca ctaagtatcc tgaaggctgg gttcctccaa agacagctaa caagaagatt 60480 gatgaaaagc atgatgcaaa actacgatat gattgggatg acttagcaca acgtatcaaa 60540 gaaaatggtg gaatccgaaa ctctgtatta gaagcttaca tgcctaatga gagttcttca 60600 ctagcaacta atacgacaaa tggcttgtac ccaattcgtg actttatttt aactaaaaag 60660 tctgcaactg gtaacgtact gtttattgtt ccagattatg aagaactgaa gtatgtctat 60720 gaaattgctt gggatattga cacctttgat atgattgatt gttatgcaat tgttcaaaag 60780 ttcactggtc aggctatctc ttcagacttc tatgttgact atgcaaagtc taagaaggta 60840 tcattggctc aagctttgaa gtacatgatt tatgccaact cggtaggtat gaaaaccatg 60900 tactacctta acagtcgcat tggtgtaggt aaatctgcac tgcaagatgc ttattgcgag 60960 ggttgtggtg tttagtttta acaactatga gggtcgtaaa agaccctcta aaaataactt 61020 tggagagacc atgaaagatt taatagaaaa acatgagcga cctatatact tgctccataa 61080 gcctcggaaa acgatgtact atgtgagtag cacagacatg atgataaaac aaaatgatga 61140 ctcatgggtc gatggcgtct cttacatctt tacagcagat ggtaaaatct acgcaagacc 61200 ttatgagatg tttaacaaag aaaactggga agttttagac agaaaacaag ccctagaaat 61260 gataaagaaa ggagaaatca cgctatgatt aaccagcacc caatcttttt aggtggtgag 61320 agaaaaactt ttgactcact taataaacac tacccaaaaa tctttgaact ttataaacaa 61380 caaaaagcac aagactggtc agaagatgag ttcccttttg aacaatcacg tcttgatttt 61440 gagagtgtcc cagcatcaat gtcaggtgta atgcttgaga ttcttaagtg gcagtgggaa 61500 gcagataccc aagttgctaa gagcttggca tttgcctttg caccctttat ctctgatgac 61560 atctatgcaa ctgcaattat gaagcagtct gagattgaaa acctacatgc tcttacttac 61620 tcagagattg taaggcaatg tattaaaaac cctgaaacca tcttagatga gattaaccag 61680 aatgttgctg tgcaagaccg attaaaaact gtgaatcgtg ttcttgaaga attactggat 61740 gaaggtataa actaccgtct gagttatgtg cgtgattcac ttctggacaa agacccttta 61800 cacttccata aagtgattct gaaaggtcta tttgcagtga ctgcactgga aggtatatct 61860 tttatggcat cctttgcatg tacttttgca cttgatgctc aagataaatt tcagggtatt 61920 gctcaagctg tccagaaaat tatgcttgac gaaatccttc acactaaaat tgatattgaa 61980 gttttaaaag aaactttaag agatgatgag tggcagaaag cttttcaaca aattcttcca 62040 gagattaaag taatcttaga tgaagtagtt gaaagtgaag agaaatggtc gtattatatc 62100 ttctccgaag gacgtgctgt agttggccta aatacaaagc ttcttcatga gtgggtttac 62160 tataatgctg ccccactgta tgatatgttt ggcattcaaa gagattttgt agctcctaaa 62220 gaaccacctt tgaaatatat gattaagaag atggaaattg ataaagagca gaatgctaat 62280 caggagcaac agaatggcgc gtacctattg aatactgttg tagatgattt gaatagtgga 62340 tttttagagg ttccttaatg acttatgtaa tttactccaa agctggatgc cctcagtgtg 62400 agactgcaaa gaattttgca aaagctcgtg gtattggcca tgttgtgaga atgttagggc 62460 aggattatga actatcagac ctgatggaga ttgcacagat gccagttcgt cagatgccat 62520 tcatcatgaa aactgatgga caaaacctaa aacctgttgg gacgctacag aattttatgg 62580 cagaggtgaa taatgcttaa acgcatttgg gaaggtttgg ttgttgatgc accagctatt 62640 gtgattggta tgcttattgt taacctattt actgactttg aacaaggttc attgtttgga 62700 gccatgttac tatgggttat ctttgaaata ttagagatac agttaggtat cactgaaaaa 62760 ctaagaaaac tctttgtgaa gttttctaaa aagatttaaa atgaaagggt ctcttcggag 62820 acctttttag catgtaaagg ggcaataatg aacaaagtac agattattaa aaagagtggc 62880 tcactcgaag aacctgatat caaaaaagtt ttagcagcag tcacaaagtc agctaatagg 62940 gttggttata aagagcttcc accagatgtt actcaagctc ttgagtcagc atttatgagg 63000 attctggtaa aatctactaa gcagaataat ttactcgttt cagtaaatga tattcacagt 63060 attgttgagg gtgctttggc agaagtcaat cacgagattt atgagtctta ctcaacatat 63120 agaaattacc gtaaagaagt tgctcaaaat tgggatgaac tttaccagaa gaccaaagat 63180 acactcttct taggtgacag agagaatgct aactttgaca gcagtttaat ttctacaaaa 63240 ggttcaatta ttcgtggtta tctgactaaa gaaatcttta aacagtacca tttaacacca 63300 gaggaacttg aagccattga aaaagggttt atctatatcc atgatttaag agacctaatt 63360 tttggtggta tcaactgttg cctgtttgac attggtaaag tcctgaaagg tggctttgaa 63420 atgtctggca tcgaatattg tgaaccaaag tctgtactgt cagccttaca ggttattggt 63480 gatgtagttc tttcagcaac tgcacagcaa tttggtggct ttactttagc agagattgat 63540 aaggtacttg taccgtatgc taagaagtct ctacgctatc atgctgagaa agcagcatct 63600 tatggtattc ctaaagaaca ttaccacaat tatgtcatgg agcagctaca gattgaatta 63660 actcaaggct tccagtcact agagatgaaa ctgaatactg taccatgtag tcgtggggat 63720 tttgcattca caactttgac attcgggtta cttgactcag atatgtccaa tgaagataac 63780 cgactgcaat acatgattgc aagtactctc ctagatgttc gtatgaatgg acaaggcaag 63840 agcaagaaac ctgttgtatt ccctaaactg gtttatatct atgaccagaa gagacataat 63900 gagaatatct gtcaaggcca actgtacagc aaagctattg agtgttgctc taaagcgatg 63960 tatccagatt ttttaagtgt atctggtcat ggtgctgtag cagaggcttt tgagcgttct 64020 ggtaaggtaa tttcaccgat gggttaacaa gctctatagc tcatctaaaa cgtgcctaaa 64080 cagggaaact ctacaggtgt agacaatcct gtgctaaatg atgtacgatg taagaaacta 64140 tataacatag gagtcttaca tgccaaataa cttcgaacat gaatttgaat acatctaaat 64200 gccgaacgac taaccgtgat gaatgtagcg gtgtagggtc aagcgactcg aaatggtacg 64260 ctacttagaa ataagtagaa gatatagtct ggacttactg gcgacagtaa gcagcttgaa 64320 taaagcgggt aagcttagcg aacttacctg aacaacaagt gtagagcatt tttatcacca 64380 taccataacg aatatggtga agagttttat gtaggtcgtg caaacattgg tgctgtatca 64440 ttgaacttac caatgattta ccagtattct aaagagaatg gtttagattt ctggaaagag 64500 cttgataagt acctagagat gattcgtagt ttccataaga aacgctatga aatgattgcc 64560 aatatgccag caagttctaa ccctcttgca tttacacaag gtggtctgta caaaggaact 64620 aagaagccta ctgacagggt tggttgggat attgtgaagt ccttcacagc ttcttttggg 64680 gttactgcgc ttgatgagct atctgttctt gctgaaggta aacgacttca tgaagttgga 64740 agctgtagtt ttgcatacga tgttctggaa tacatcaaca tgaaaactga agagtttaaa 64800 aatgaagatg gcttcttata tgcagtttat ggcactccag cagaatcact ttgtggaact 64860 cagctaaaac agttcagaga tatgtttggt gttatcaaag gtgtttctga taaggaatac 64920 tttacaaaca gtttccatat gaatgttgca gcagatatta caccatttga gaagcaggac 64980 ttagaagaac ctttcttcca tatctgtaga ggtggtagaa tccagtatgt cagagtagct 65040 aacccagaaa acttaccagc acttaaaagt tgtattacaa gagggatgtt gaaaggtttc 65100 tatcagggac ttaactttga cctagcaatc tgtgaacatt gtggtaacag accaaaggct 65160 gatgttgaag aatgtgaggt ttgccattca cacgatatct ctgtgattaa cagggtgtgc 65220 gggtacttgt cattcacaaa aattaaaggt cagtctcgaa tgaatgacgc taagatggca 65280 gaaattaagg atagggtttc tatgtaaaac ttgacatggt ggtgtgagtc ttgataggct 65340 tgcatcacct ttttatttgg agttacatta tggacttgtg gctttatgta gcagtttgtg 65400 ggattgtatg tctgataatc ttatttattc ttggagtaat gcgatttaga gacatcatac 65460 agtcagattt tttgcctgag tttgccatga tagttggggt tattaccctt tgtgtcttgg 65520 cagtgttcta ttcatacaaa actgtgatat ggatggaggc aaacaattgt gtaaaaactc 65580 atcagcatcg tgaggttact cattttgtga gtgtacttag tggtagcacc actatacttg 65640 tcccacaaac ttctgtagag tatctttaca catgtgataa tggtaaaact atatggtgga 65700 attaacaatg acaacactct taaaagtatt gatgcccata ctacatatag cagtcttctt 65760 ctttggtatt agtgttatgg tatggggctt ttcagaccca caatggagtt tttcatatca 65820 tggtcagatg gacttatggt catgcttcaa accattttta gggttagcta tagcattcag 65880 tgcattacca actaaggtga aattatgatt aagttgaacc aaaaacagct agagtggatt 65940 aaagactacg cctcagagtg tggctcttgt gaaaagaacc acctaagata ctcaacattc 66000 catacgacct tcacattgta tattggtgac aatgttctaa gtgactccgt agaagataat 66060 gtagcattac ctaatgagtt gcttgacaaa ttagctgtag tcactggaac ttggtctgaa 66120 gaagacggtc atgaattatc taacgatgtt gtcttctaca gtcttgaaaa cattatgaat 66180 ccagagtaca ttatgttaat gacttgtgca caagactgtg tgccattaca aaacttcatt 66240 aaagaacact gtgaagagtt tattactaaa caggttcctt gtcaggtggt gtttgaatga 66300 gtaaaaggct taaataatat tggtgaggta actagatgaa ttacatggag attagaccat 66360 ttgacacagc taatggtgaa ggggttcgtg taagcctctt cgtagctggc tgcaaacatc 66420 actgtgaagg ctgctttaac agggagtctt ggaaatttaa tgctggtaaa gagtttactt 66480 atgcaaacct ctacggcatc attaagttaa tggatgataa tgctatcagt ggactgtcaa 66540 tacttggtgg ggagcctctg gatgacagaa acattcaaga ggtcactaat atatgcaagc 66600 atattaaaac cgtttatcca gagaagtcta tctggctctg gacaggtttt cagttacacg 66660 aaaaaattca cctagatgtg atgaaatacg ttgacgtggt gattgatggt aagtatgatt 66720 catctaaacc aacagttaag ccgtatcgtg gttctgataa ccaaaacctc tggagaaaag 66780 agtatgggtg gcaaggtgac tgtcagtgga gagccgagta agtctcgtcg taaagtgggt 66840 tacagaaaag gtgagataat ggttctttct tttaacagtg ctttattggg tacttataaa 66900 attaagaccg agctacttga tgaatggaga aagtatacaa actccctttt cggtaatgtt 66960 ggaatggaag ccttagcaga gattgagaag gctggaacat ttgaagttgt tggtaaaggt 67020 aactacacaa tgttctacaa aacaaattta aacgttggtg acagtattgt tggtgtcact 67080 gaagaagaac ttaaaacatt ttgtgaaaag attgagagag atgcgaaatg ggactctgga 67140 acagttttaa atcaaaagta aaagcagcac tagcatcatt aggcatactc actggcattg 67200 atgtgactca tcttatgcag aactttaaga tggatgagaa gctggctaat gagattatga 67260 aaagtatcta tgtaggccgt ggcaaaggtg gtaagaaaca agcccaccgt ccgtctggtg 67320 cagcagctat taaacgagca gctaagaaag ctcgtaaccg taaacgtaat aagaaggcta 67380 aataatcatg agcaaagttt ataacactcg taaattacag attttcgtac tgtgccagtt 67440 tatggctaaa gaatataact tctactattg tggtacaggt tttattagcg atgatgatgg 67500 ctcatacctc ccatttaaag aagctgtgaa actctttaat gaagagaaaa gctctaagaa 67560 agatattgaa aaggttaagc taacctacag caagaaagat aagaagatta tctgcctaga 67620 taactttgtg aaagttactg gagaagcaaa agagtttatg gatgagagtg aaatctcatt 67680 cacaagcatc ttgaaagtag ctcagtaaac agatactata aggggactgt aaaggttccc 67740 tttttatttt ggagataata tgtatctgtc aaatctgaaa cgttctgttg caatgtcagt 67800 gttaagactc agttttgagg aacgtcaaga gttcattgac tcccaccaat acgacccttc 67860 caactccaat cacatgattc tctggaatcg tgagagtact cgtgaaagag cattatttcg 67920 atattatcca cactacacca tagacaacct gtatgaatgt tttgttgtga agaacaccat 67980 taaagtactc aataaacttt gcagatacac aggcagtcaa tccttcacat taggccacca 68040 caaacctgtt acaaaaggtg gtgaacatca ctgtgcaaac tggtttattc agactaaagc 68100 tgataaccag aagcaaggag atagcctcct aagtatccct aagatgacct atgaagagca 68160 agagagatat atcaaaaata atatgccaga tgtgcttgac aacaactata cagatttggc 68220 aatatctctc ctgttgaagt tcgagatagt ttatagggca acttacaatg gctaaagaaa 68280 agtgggagat tttaccatta gtcagtgaag gcggtaatgg ttgtgaaatg tacatgatac 68340 gtggtcatgt tccagagcca attgcacttg agatggtaaa taattataca gatggttcct 68400 gcaaagactt aggagaacca actgtcaagc agcaatgggt aaagcctgtg ccagatagta 68460 caggaaactg tagtgtactt tatcacgttg tagaccctgt aaaatgcaag tctgcaatgg 68520 cagtaactaa cgtaactttt gattgagaga gaaaattatg aaaacatcta tacgtgttac 68580 agttcattca ccaactaaag gaactcatga agaagagttt aacatcatcc aatttccttc 68640 tggtgagatt ggtggacact tttcaccaga gtttgttgat tttactgctt atgcagcatc 68700 atctatcaac aatgtgatta tgattgtaaa aggttatgat aaggacacat tgtttgctgt 68760 ggcacttgct aaagaagcaa ttgatgattt agtacctcat aagtttgcta tgaagactgc 68820 tatcttttac tatttgccaa atgcacgtta cgaccgtcac atgtttaaag gtgatgcagc 68880 agctttgaaa gtgtttgcac aacaggttaa tgcaatgggt tttgatgcag tctgtgcagt 68940 tgaccctcac agctatgtac cagataacct gtttaactgc ttccagagta ttcctcaaaa 69000 ggaaattgca gtccactatg caaatgaccc acgcattgat ttcttggtag ccccagatgc 69060 aggtgcagct aagaagactg aagagactgc taaagaggtg gataaaccat acatcacaat 69120 gtctaaagta cgtaacctta agactggtga aattactggt atgcgaatcc ttgatgatgt 69180 tgatttgacc gataaaactg tcatgattct cgatgatatc tgtgatggtg gtcgaacctt 69240 catagaagca gctaaacatc ttcgtgaagc aggtgcaaaa cgtgtggaac tctatgtaac 69300 tcatggcatt ttctctaaag gtgttgaaaa cttacttgac aatggtattg accatatcta 69360 cactacaaac tctttagggg aagctaaaga ccgtggctta acacattatg cccaagttac 69420 tgtaattacc attgattgaa actttatagg gggtttcaaa gccccatttt gagagagatt 69480 aaaaagatga ctaaatcact ttatgcagta ccagcaggtt taaacgcgga tgcttacaaa 69540 tctggccata tttatcagta tcctagtgca acagagtacc taatgttcaa cctgacacca 69600 cgtagtgaca aatggtttaa cagcccttta gcaattgacg gtgtagtggc ttttggtatt 69660 caacgttttg ttaaagatta cctgatagac cactggaacg ccaccttctt tgaacgtgac 69720 aaaaaagaag caattgacga aatcttagaa gtcatgaacg gtgttctggg taaagatgct 69780 attggtcgag aacattggga agcactccat gacttaggtt atctaccagt tgaagtatac 69840 gctgtagaag aaggcacagt tgttcctatg cgtgtaccaa tgattgtctt ccagaacact 69900 gtctcaggtt tccattgggt agcggggtat ctggaagatg ctttctctgc tgagatttgg 69960 aaggcttgta ccattgcaac tattgcattg cactacaaac gtatctgtaa gaagtggtct 70020 gaccttactt gtgacaacga cttgcatttg ccttatcagt gccatgactt tgctatgcgt 70080 ggtatgtccg gctttaccga tgacgcattt aacgctgtag gccacttaac cagctttaaa 70140 ggaactgata gcttccctgc tgtgtataca gctaaacgca tctatggaca gtcctaccca 70200 atctctgata ttggtagctc tgtaccagcc actgaacact ctgtaatgtg tgcaaacatt 70260 gcttgggaag gtggtagtga gttgattgaa gaagaaagac gctttaaagg tgagttacaa 70320 accttccgtc gtttcttaac agaaacttac ccaactggta ttgcaagtgt tgtttcagac 70380 acttataact tctggagaac tgtatcagtc atattaccag aactccgtaa agagattatg 70440 gaacgtaatg gcaaactagt aattcgtcct gattctggag accctgtaca tattgtcaca 70500 ggatacaaag caatccattt agagtgtgct aaaaaggctt attacgaaca cctaagtaag 70560 ctggaagcca gcgacacaat gctgaatgct gttctgaaca tgaagcttga aaacatcaat 70620 tatggtattg ctggatggct actgtcagaa ggttacgaaa tggttgttga cagagaagac 70680 tttgaagttg ctgatacagt gctgttgaaa aatgcttata tggttggttc tgcaaacgtt 70740 gtaacacgtc ctgtagcgga gattgatgga gctatcaaga cactgtataa catctttgga 70800 ggaactatca actctaaagg ttttaaagta ctggatgagc atatcgggct tatttatggt 70860 gactctatca cgttggaacg tgcaaacgaa atactgaagc gtttgtatga aatgggtttt 70920 gcaagctcta acgtagtatt tggtgtaggt tcttacactt accagtacat gactcgtgac 70980 acttttgcat ttgctgtcaa agcaactctt gcaagtattg gtggtaaaga gattatgctt 71040 gcaaaagacc ctaaaacaga tagtggtgtt aagaagtctg cttttggtgg tgtagcacct 71100 atgtgggatg gtgaaaatct taaagctgta gatggctatg gattccagag ctttgcagat 71160 gcacttgaac acccagcttg tgctttacgt ctagtcttta gcgactctga gcagttcggt 71220 tacacaactc ttggtgatat tcgaaataat attgacaagc agctttaaaa gtatatgata 71280 agaggctcct acgggagcct ttttaatttc tggagaagat tatgaaaatc aaagagatga 71340 acatcaacat tgtcttagaa gagcgttggg agaacatcaa gaagcctgaa aatggtcata 71400 agttcctcaa taaaatctta gtagcagcta aagaagaact gactggcaag attgcagcag 71460 caatcacaat aaaggtctgt gtaaaaggtc ttccagacaa tcaccaattt gcacttgacg 71520 agtttaaaga gagcttctac aatccaaaca aacagatgct tgaaagtaac tttgcagtgt 71580 ctacaagtat cgtccatgac agaagcttta tcctttacaa gaatatgaga ggtgagtcat 71640 gcaagcatat tggatagaaa ttttgctatc acttggtagt gtagcagtgt ttgtttatct 71700 tctttgtaag tactttgcag agtacaagaa gtgtgattac tgcaacggag aagggtatac 71760 aagagcaggt tgttgcccta tgtgtggcgg ttctggtaaa atgtttaata agtaatttaa 71820 cagtaaacta agaggaaagt attatgcgca tggtaaatga ccacgcagaa gtgattaaga 71880 gttcaacttc tttagagacg tctcaagcac agattacaat gacacctgag atgttcagcc 71940 ttttgagttc tggtgtatat acctttaaag aaagggcagt gattcgtgaa ctgtcatgta 72000 acgcagtaga tgctcagaaa gaagctggaa aagagaacat cccgttccat gtgcatttac 72060 ctactcgttt tgagccttac tttgaagttc gtgattttgg aactggattg actcatgata 72120 aagttatgag tttgtaccta aactacgggg cttctacgaa gaatgactct aatgactaca 72180 ttggtgcaat gggtatcggc tcaaaatccc catttgcaat tgctcagtca ttcacagtat 72240 ccagctatgt tgacggtgtt gttaacaagt actctgttta ccttgagaat ggtatccctc 72300 aagtaactaa gctaaccacc aacccaacga atgaacctaa tggtttagct gtacgtgtag 72360 cagttgctga ccatcgtatt tcaaagttct ttgaagaggc tggtaatgta tactcatact 72420 ttgctgtaaa accagaaagt aatattgagt atgacgatgt attagcagat atgaacgtca 72480 ttgcccgtga agaaggtgtc tatgatgcca tgattcataa gcaaagctgg cgttctagtg 72540 gtaacaggac agagtttaat gtggtgatgg gtaacattgc ctaccctgtt aatatggaag 72600 cattacttgg tgatgatttc ttcaaagtat tgccagaatt tttccgtagg agcgtagacc 72660 ttgtaaacat ctacatgcct attggttcag ttgctattgc agcttctcgt gaagcattgc 72720 agatgaatga cacgacaaaa aatgttatca ttgaggctac taaaaagata actgaagcaa 72780 ttacaaagga tgttatcaag aaagttaata gccaacctac actcatggat gctgcacagg 72840 cttatgctga gttacgtttg aactcacgag agatgtttaa tgctgtgtgt ccaaagctag 72900 agtggggagg cgttaagctt gattctctgg aagaagaatt actaaacatt cgtcgtggaa 72960 ttatctacgc agaagacggc tcagttgtct atgaacgcga tggtaaaggt aatattaagg 73020 ttgataggaa cggaaacaac atccctaaag tagattatct ttataatcca gttgcttatg 73080 ttaagtttaa ctctttagag agtaagattc gtgcaacagc actttcctac actcaagagg 73140 cgagtatgtt caatatcttt ggtgcaatgc gcaaaagcca aattgaacag tttttgtttg 73200 ttatcaatga ccgtcgcaat aaaaatggta ctgagaagac tgtaggacgc aatcagattc 73260 tgcgtggtgc atgtcgagac tatgccagtg agtcaagtct gtttcacaga tacaatggta 73320 ttgtctttgt attctcgact gaaaaagagt tagacgacct aatcaatctg cacaaacttg 73380 ataaaagctt gttaaagatt gtgaagatgt ctgataagga acaccattat cagcgtaaag 73440 aagctgtaag aggtgttgta aaactttgga aagctgttcc agcagaaggt gtagcttcct 73500 ataaagaggt ttcagaggac tttgatacaa ttgaagaacc tcagttttat attaaggcag 73560 taggcgacac agttgatggc gaatgttttt gctcatctcc agaagatgta gctaagtcag 73620 ttgccaatgt cattggaaag acagtatatg ttttccgaaa agcaaattgg aaaaagatac 73680 cagaagactg gattgaagta gatgagaagc tcttgaacga cagcttaact gatgttcatt 73740 ggattaatca taacagatat atgacacgta tctatatgaa tggtgtcctc gaccttacaa 73800 gcagttggat tattgccaga aactttacgt tcaataacag aaagatttct cgtggttatt 73860 gttattcacg agatacaaac aaaactatct tcttagaagg taatgaagat gctgttgagg 73920 caatgtttgg taaaatccaa tacgttgctg caccgtttgc atacacttac actattagta 73980 ggttgcaaac tttgaaagat tgccttgaca atgatacaaa gctgtacaag aaaattaaga 74040 aagctggtga ccgtatggtc atcaaggtga caaactatct ttcaaaaaga aaacaagaaa 74100 acttcttgct ttctcattta gattggaata aagtgtcacc tattgaagtg agtaagttct 74160 taggctttga tgtgaagtgt gttccagaag gaactacaat ttacgattaa agtgtttgac 74220 aaggggcttc aaagcccctt agaatagcct tacaaaatga tttattaact aacaagagag 74280 agtaataaga tgactactaa aactaaagca cagattgacg cagaaattta caaactggtt 74340 aaagaaggca agctgactaa aacagctatt gcacagaagt tcaatacttc aacccgttca 74400 gttggtcgtg ctgtagagcg tcatgaagca accttaaagg gtaagaaaaa gacagcttcg 74460 acaccagcta cgaagacttt gaagcaagtt gctaagacct ttaagaagaa agctggcaaa 74520 ccagttgaaa aggtcgttaa agacactgta cagaaagttc cagtaaataa actgcacgaa 74580 gctatgcaga aagatgacaa gattgagtac atgattactg gcgactctgt aattatgact 74640 tacggttcag aatctgaaat tgttgagtct actcatccga actatcaaga gattgtagtc 74700 catgttgtga aaggtgagtt caagaaagct ttcgaactga tgaacattcg taaatctatc 74760 gaaaacttca ctcagggtgc tatcacaatc aaaggtgaca agctattcta cggtgctgtt 74820 gaaatgcgtt ctactctggt tgaccgtatc cttcacatga tgaagactgg tgataaaggt 74880 tttgaacgac ttgtaatgtt cttcgaaaaa ctgatggaaa acccatctaa agactctgta 74940 gaacaacttt ggggattcgt atctcacctt gatgttgaaa ttgatgaaga aggctacatc 75000 attggttgga agaaagtctc tactcgtgaa ggcaagctgg ttgactctca cacctacaaa 75060 gtacctaatg atttaggtaa cattgtagaa atgccacgtt ggatggttga taacaaccgt 75120 aacgtaactt gctctcaggg tcttcatgtt ggtgcttggg attatgttcg ttgcttctca 75180 ggtgatacaa tcctgaaggt tcgtgtccat ccacgagatg ttgtatctgt tccgactgat 75240 tacaacgata tgaagatgcg ttcatcccgt tatgaagttg cagcaatcgt tgataatcaa 75300 cgtaaagtgt tgaaagcatg ggacggtaag actgaagctt tgcatgtcat cgtcggtact 75360 gctggtgaac tcatctccca acgtaaacgt gaaatctaat aagtaatttc ttaaaaggct 75420 gcttcggcgg ccttttttat ttgtattttg tgcagagtgc tgtataattg ttgtcacgat 75480 aaactaaaca ggagaaccaa tgaagaaatt gattctagga ttgtgcttaa tgtttacagc 75540 acatttatct tatgcagttg actgcccaga gctatcaatt agccaaaaag ttaacatgtt 75600 aaaagcttac cagtatggtg agaacaacat ggggaaaggc tggggtatta ctctagcagc 75660 tatagcctta caagagtcag agttaggtct gaaggtagag aataaaaaga cccatgacta 75720 tggtattttc cagaatcact tgaagactgt tgtaaagcgt aacaaaatta gtcctaatgt 75780 ggctaaaaag aaactcttaa aagattttga ctatgcagca aaagagacac ataaagagct 75840 tgagttttgg actaaggtac atggtcaccc gaagtcaaag aagactttac aaaaagtttt 75900 agcatcatat aatgctgggt attcgtacaa aatccctaaa gctaagaaat actctcaaga 75960 tgtctataac aatatgaaag ttattgctca atgtgaattt gcaacaaaca tttctaaggt 76020 aaatcatgaa aaaattaaga aagcctgatg aagtcctgtg ccacgcttat gacttgcatc 76080 ctcatgagtt aggtcttgat tcctgtgtat ggactccaga acagtgcagg gattttgaag 76140 acactgcaag agaagttgta tgttcacttg aagagttcca cacatcagaa ccaattgtga 76200 acgttgtgga taaagaaact ggacaagcta taggtgtaag tcgtgatagt ttagtcatag 76260 tcaataaaga ccttgtagaa aaaggtaacc tcatcttagc agatattgat ggtgttctta 76320 caaattttaa tcacgaagat tgctcaacgg aattgactga tgggtcattc tcacagtaca 76380 ctaatcttct tgactctgta agagcaaaac caacatatgt ttttagtatt attgatgcaa 76440 ttgctaatca tgctaccatt ggactcttga cagctagagg tgaatctcag agaataccta 76500 ctgagatgtt tttaaggcat aacatagagc atgattacat gctttttatg cgtggttttg 76560 gaactaactc tataagtgca gaaagtttaa aagctaggat gattcagtct tgcattcttc 76620 cttactttaa tatagtatgc tttatagaag atacagagaa gaatgttcag aaggtaaaca 76680 gaatccttcc acacattaaa accatgttag ctaaacattg agagaaaaac ttatgaacaa 76740 tatcattacg gtagcactgg acgatacgac aaacaaatct gtagtagttc gtaaattgat 76800 tcaaggtaac tttgaaggta aaatttttcg tgctgtcaat gtaaaagctg atggcagcat 76860 tcgtgaatat cgtgcattgt tgaacgttaa gaagcacgta aaaggtgttg gttcaacgac 76920 tgcacacaaa gaaaacctga tgactatcta tgatatgggt aaggcttcag agttaggtgc 76980 tgaaggtatc gttaaagaag gtgctccgta tcgctctttc aatctggaaa ctactcttat 77040 gctttccttt acgagtggtt ctaaaacaat cacttatctc tttactgatg ctgcaacggt 77100 atctgctatt aaggatggca ctgtcaaagc tggcgtagtt gctgctgcaa aagcttcttc 77160 gatggctgca aatatccttg ctaaagtcct cggttaaggt taagatacag gctccttcgg 77220 gagccttttt catttcagga gattgttaaa tgacatttaa agagttctgt caagctactt 77280 tcataattgt tttcttagtt ggggcaggtg tctggggag atactcttac agagactacc 77340 aagttgctga agctgagcta aataatgaga aactaataag tgttgctaaa gatgcttatc 77400 aggaaggttt agccacactc agcaccaatt acaaaaatga tttgaaagac gtgcttgcta 77460 agaataagca tacaaaagag gtactaacgt atgaaaagac taagccagag ttttataatg 77520 tttgtgttac tgataattat gtcagggtgt tcaacgaaca aagtgaacag tacattcaaa 77580 aactcccaag taagtagagag tgacaagtac actcaagaag attcaagatt cactgtcaaa 77640 ggtaatactg gtagtgatgt ggcatcagcc cttgagtttt accgtgatgg tttttaccag 77700 tgcacaatca aagctaataa ccttattgat atgattttat taggaaacaa acagcaatga 77760 cagagaatga agacactttc tatgtagaag ggtacttact gctaccacga ccaaaagaaa 77820 cttatatgcg ggttgatttc tcaccaacca ttatggataa cgtgatgtgt catatcttta 77880 tgcaaggtgt cacagcacaa cttaagcatg ttggtaaaga gtgcaaaata aaggttgaca 77940 ctcatccaga aatcaaagag aatcactaca catggttctt accagactct aaagaaatct 78000 tagcagttct taaaacgagg aaatgattat gcaattccag ccaacaaatc gtgggttttc 78060 ttatgcagaa tttaaagatg ctaaaggaga gatttgtact ttacaagaaa gttcatcata 78120 tgaaccatgt atctggttag gtgctaaaga ggtctctgtt cagtacctag atggtggctg 78180 gaaaacactt gatatcccag cattagtagg caaagatttt gtaggtaacc aaagaatgaa 78240 actcaaccaa gaacaggtga gagagttatt accatacctt cagtactttg ctgaaaatgg 78300 tgaattacca gcagaggaac ttacaaatgc agattaatgg aagagatttt gtagccgttt 78360 actacgagaa cgataaagaa gttg 78384

Claims (11)

시가톡신 생성 대장균(Shiga Toxin-producing Escherichia coli, STEC)에 특이적인 사멸능을 갖는, 서열번호 1로 표시되는 염기서열로 이루어진 박테리오파지 ECOH1.
Shiga Toxin-producing Escherichia Bacteriophage ECOH1 consisting of the nucleotide sequence shown in SEQ ID NO: 1, which has a killing activity specific to E. coli , STEC.
제1항에 있어서,
상기 시가톡신 생성 대장균은 장관출혈성 대장균(Enterohemorrhagic Escherichia coli, EHEC)인, 박테리오파지 ECOH1.
The method according to claim 1,
The E. coli Shiga toxin produced Minister haemorrhagic Escherichia coli (Enterohemorrhagic Escherichia E. coli , EHEC), bacteriophage ECOH1.
제2항에 있어서,
상기 장관출혈성 대장균은 대장균 O157:H7인, 박테리오파지 ECOH1.
3. The method of claim 2,
The intestinal hemorrhagic Escherichia coli is E. coli O157: H7, bacteriophage ECOH1.
제1항에 있어서,
상기 박테리오파지는 기탁번호 KFCC11731P인, 박테리오파지 ECOH1.
The method according to claim 1,
The bacteriophage is the bacteriophage ECOH1, which is the accession number KFCC11731P.
제1항의 박테리오파지 ECOH1을 포함하는, 항생용 조성물.
An antibiotic composition comprising the bacteriophage ECOH1 of claim 1.
제1항의 박테리오파지 ECOH1을 포함하는, 사료 첨가용 조성물.
A composition for feed addition comprising the bacteriophage ECOH1 of claim 1.
제6항의 사료 첨가용 조성물을 포함하는, 사료.
A feed comprising the feed additive composition of claim 6.
제1항의 박테리오파지 ECOH1을 포함하는, 소독제.
A disinfectant comprising bacteriophage ECOH1 of claim 1.
제1항의 박테리오파지 ECOH1을 포함하는, 세척제.
A cleaning agent comprising the bacteriophage ECOH1 of claim 1.
제1항의 박테리오파지 ECOH1을 인간을 제외한 개체에 투여하는 단계를 포함하는, 시가톡신 생성 대장균에 의한 감염성 질병의 예방 또는 치료 방법.
A method for preventing or treating an infectious disease caused by a cytotoxin-producing E. coli, which comprises the step of administering the bacteriophage ECOH1 of claim 1 to an individual other than a human.
제10항에 있어서,
상기 시가톡신 생성 대장균에 의한 감염성 질병은 세균성 식중독, 출혈성 대장염, 용혈성 요독증후군 및 혈전성 혈소판 감소성 자반증으로 이루어진 군에서 선택되는 것인, 시가톡신 생성 대장균에 의한 감염성 질병의 예방 또는 치료 방법.
11. The method of claim 10,
Wherein the infectious disease caused by the cytotoxin-producing Escherichia coli is selected from the group consisting of bacterial food poisoning, hemorrhagic colitis, hemolytic uremic syndrome, and thrombotic thrombocytopenic purpura.
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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN116903710A (en) * 2023-09-12 2023-10-20 山东省农业科学院畜牧兽医研究所 Phage targeting protein molecule and application thereof in identifying shiga toxin-producing escherichia coli of O103 antigen serotype

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20140140698A (en) * 2013-05-30 2014-12-10 한국외국어대학교 연구산학협력단 Bacteriophage of Escherichia coli and uses thereof

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20140140698A (en) * 2013-05-30 2014-12-10 한국외국어대학교 연구산학협력단 Bacteriophage of Escherichia coli and uses thereof

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
BMC Genomics. 2015, Vol. 16: 271, pp. 1-13.* *
GENBANK: KP869100.1, 2015.04.29. *
GENBANK: KP869110.1, 2015.04.29. *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN116903710A (en) * 2023-09-12 2023-10-20 山东省农业科学院畜牧兽医研究所 Phage targeting protein molecule and application thereof in identifying shiga toxin-producing escherichia coli of O103 antigen serotype
CN116903710B (en) * 2023-09-12 2023-11-14 山东省农业科学院畜牧兽医研究所 Phage targeting protein molecule and application thereof in identifying shiga toxin-producing escherichia coli of O103 antigen serotype

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