KR20230171294A - 과수화상병 및 가지검은마름병에 특이적인 신규 박테리오파지 및 이의 이용 - Google Patents
과수화상병 및 가지검은마름병에 특이적인 신규 박테리오파지 및 이의 이용 Download PDFInfo
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- KR20230171294A KR20230171294A KR1020220071690A KR20220071690A KR20230171294A KR 20230171294 A KR20230171294 A KR 20230171294A KR 1020220071690 A KR1020220071690 A KR 1020220071690A KR 20220071690 A KR20220071690 A KR 20220071690A KR 20230171294 A KR20230171294 A KR 20230171294A
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- Prior art keywords
- bacteriophage
- erwinia
- blight
- erwinia amylovora
- pesticide composition
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- A01N25/00—Biocides, pest repellants or attractants, or plant growth regulators, characterised by their forms, or by their non-active ingredients or by their methods of application, e.g. seed treatment or sequential application; Substances for reducing the noxious effect of the active ingredients to organisms other than pests
- A01N25/02—Biocides, pest repellants or attractants, or plant growth regulators, characterised by their forms, or by their non-active ingredients or by their methods of application, e.g. seed treatment or sequential application; Substances for reducing the noxious effect of the active ingredients to organisms other than pests containing liquids as carriers, diluents or solvents
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- A—HUMAN NECESSITIES
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- A01N63/00—Biocides, pest repellants or attractants, or plant growth regulators containing microorganisms, viruses, microbial fungi, animals or substances produced by, or obtained from, microorganisms, viruses, microbial fungi or animals, e.g. enzymes or fermentates
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Abstract
본 발명은 기탁번호 KACC 97038P인 박테리오파지에 관한 것으로, 상기 박테리오파지는 에르위니아 아밀로보라 (Erwinia amylovora) 및 에르위니아 파이리폴리아(Erwinia pyrifoliae)에 대해 특이적인 용균활성을 보여, 과수화상병 및 과수검은가지마름병에 방제 효과가 있으며, 과수화상병 및 과수검은가지마름병의 방제를 위한 미생물 농약으로 활용될 수 있고, 항생제 대신 사용될 수 있으므로, 항생제 저항성 균주의 출현을 막고 환경에 영향을 끼치지 않아 안전하고 효과적인 과수화상병 및 과수검은가지마름병 방제를 기대할 수 있다.
Description
본 명세서는 과수화상병균 및 가지검은마름병에 특이적이고 강력한 용균 활성을 가지는 박테리오파지, 상기 박테리오파지를 포함하는 농약 조성물, 및 이를 이용한 화상병 및 가지검은마름병의 방제방법에 관한 것이다.
과수화상병(fire blight)은 대표적인 세균성 식물 검역병 중의 하나로, 에르위니아 아밀로보라(Erwinia amylovora)가 그 원인균으로 알려져있다. 과수화상병은 배 또는 사과나무 등의 꽃, 가지, 열매를 까맣게 변화시켜 불타 화상입은 것처럼 검게 말라죽는 증상을 보인다. 에르위니아 아밀로보라는 곤충이나 비바람에 의해 전염되어 꽃, 꿀샘, 기공, 피목, 상처 등을 통해 기주체로 침입하기 때문에 전염성이 높고 배나무, 사과나무, 살구나무 등 70여종의 식물을 침해할 수 있다는 특징이 있어 세계적으로 화상병에 대한 피해가 발생하고 있다.
과수화상병은 확산 속도가 빠른편이기 때문에, 한 그루에서만 증상이 나타나도 과수원 전체를 폐원해야 한다. 이 때문에, 과수화상병은 당해의 수확을 망칠 뿐만 아니라, 농가에 장기간동안 피해를 줄 수 있다.
또한, 과수가지검은마름병은 토착 세균성 식물 검역병 중의 하나로, 에르위니아 파이리폴리아(Erwinia pyrifoliae)가 그 원인균으로 알려져있다. 과수가지검은마름병은 배 또는 사과나무 등의 꽃, 가지, 열매가 검게 말라죽는 증상을 보인다.
과수가지검은마름병은 확산 상대적으로 느리지만, 한 그루에서만 증상이 나타나도 과수원 전체를 폐원해야하며, 반경 100m 이내의 과일나무를 뿌리째 뽑아서 태우거나 땅에 묻는 방식으로 폐기해야한다. 이 때문에, 과수가지검은마름병 또한 당해의 수확을 망칠 뿐만 아니라, 농가에 장기간동안 피해를 줄 수 있다.
상기 질병에 대한 대응방법으로서 토양 수분을 감소시키고 비료 영양소의 균형을 유지함으로써 화상병의 감염 및 확산을 제어할 수 있는 방법, 감염된 과수나 검게 변한 가지를 병원균이 휴지 기간을 갖는 겨울에 제거함으로써 화상병을 치료하는 방법 등이 알려져 있으나, 본질적인 질병 발생을 제거할 수 없다.
본 발명자들은 에르위니아 아밀로보라 및 에르위니아 파이리폴리아의 방제 방법으로서 박테리오파지를 이용한 방제(치료) 방법인 파지 테라피를 연구한 결과, 배 과수원의 물로부터 분리한 신규 박테리오파지가 에르위니아 아밀로보라에 대해 강한 용균성을 보임을 발견하였다.
일 양상은 에르위니아 아밀로보라(Erwinia amylovora) 및 에르위니아 파이리폴리아(Erwinia pyrifoliae)로 이루어진 군에서 선택된 하나 이상의 균에 대해 특이적이고 강력한 용균 활성을 가지는 박테리오파지를 제공하고자 한다.
다른 양상은 상기 박테리오파지를 포함하는 농약 조성물, 구체적으로는 과수화상병 또는 가지검은마름병 방제용 농약 조성물을 제공하고자 한다.
또 다른 양상은 상기 박테리오파지를 유효성분으로 포함하는 소독제를 제공하고자 한다.
또 다른 양상은 상기 박테리오파지를 유효성분으로 포함하는 세척제를 제공하고자 한다.
또 다른 양상은 상기 박테리오파지를 이용한 과수화상병 또는 가지검은마름병 방제방법을 제공하고자 한다.
본 발명은 Erwinia amylovora(에르위니아 아밀로보라)에 특이적인 용균활성을 갖는, 기탁번호 KACC 97038P인 박테리오파지를 제공한다.
본 발명자들은 에르위니아 아밀로보라에 대한 용균 효과, 숙주 특이성이 우수한 신규 박테리오파지를 선별하여, 이를 Erwinia phage Fifi067(이하, Fifi067이라 명함)이라 명명하고, 국립농업과학원에 2022년 8월 5일자로 기탁하여 KACC 97038P를 부여받았다.
본 발명자들은 경기도 안성 서운면 배 과수원의 물로부터 박테리오파지 Fifi067을 분리하였고, Erwinia amylovora strain YKB14808을 숙주로 하여 수행한 실험에서 플라크를 형성하여 에르위니아 아밀로보라를 용해(lysis)시킴을 확인할 수 있었다(도 1).
도 2를 참고하면, 박테리오파지 Fifi067의 MOI (multiplicity of infection) 수치가 낮은 경우에도 숙주 세포의 생장을 억제할 수 있음을 알 수 있다(도 2의 control은 박테리오파지 Fifi067이 투입되지 않은 경우이다).
박테리오파지 Fifi067을 CsCl 밀도구배 초고속 원심분리법으로 순수 분리한 후 전자현미경으로 파지의 형태를 확인한 것을 도 3에 도시하였다. 약 70nm의 머리로 구성된 포도비리대 과(Podoviridae family)에 속함을 발견하였다.
본 발명의 박테리오파지 Fifi067은 에르위니아 아밀로보라(Erwinia amylovora) 및 에르위니아 파이리폴리아(Erwinia pyrifoliae) 종내라면 모든 균주(strain)에 효과가 있다. 디케야 제아(Dickeya zeae), 엔티로박터 클로아카(Enterobacter cloacae), 대장균(Escherichia coli), 판토에아 아글로메란스(Pantoea agglomerans) 등에 대해서는 용균활성을 보이지 않는다.
또한, 본 발명의 박테리오파지는 식물 등 세균외의 다른 숙주는 감염시키지 않으므로, 항생제의 오남용으로 인한 항생제 내성균의 문제점, 식품 내의 항생제의 잔류 문제, 광범위한 숙주범위의 문제점을 해결할 수 있는 장점이 있다.
따라서, 본 발명의 박테리오파지는 에르위니아 아밀로보라 및 에르위니아 파이리폴리아 세균에 의해 유발되는 감염성 질환의 예방 또는 치료, 항생용 조성물, 사료 첨가용 조성물, 사료, 소독제, 또는 세척제 분야에서 다양하게 사용될 수 있다.
본 발명의 박테리오파지 Fifi067은 서열목록 1의 염기서열을 갖는다. 구체적으로, 박테리오파지 Fifi067는 75,307 bp의 염기서열을 갖는다.
박테리오파지 Fifi067은 15℃ 내지 70℃, 20℃ 내지 70℃, 25℃ 내지 70℃, 30℃ 내지 70℃, 35℃ 내지 65℃ 또는 40℃ 내지 60℃에서 활성을 갖을 수 있다. 구체적으로 50℃에서 1시간 처리하여도 에르위니아 아밀로보라에 대해 용균활성을 보였다.
박테리오파지 Fifi067은 pH 1 내지 15, pH 2 내지 14, pH 3 내지 13, pH 3 내지 12, pH 4 내지 12, pH 4 내지 11에서 활성을 갖을 수 있다. 다양한 pH에 노출되어도 에르위니아 아밀로보라 및 에르위니아 파이리폴리아에 대한 용균활성을 보인다.
또 하나의 실시상태에 따르면, 본 발명은 상기 박테리오파지를 유효성분으로 포함하는 농약 조성물을 제공한다.
본 발명은 에르위니아 아밀로보라(Erwinia amylovora) 및 에르위니아 파이리폴리아(Erwinia pyrifoliae)의 종내 모든 균주(strain)에 대한 증식 억제 및 사멸 효과가 뛰어난 조성물을 제공할 수 있으며, 이러한 조성물은 박테리오파지 Fifi067을 유효성분으로 포함한다.
상기 농약 조성물의 박테리오파지는 과수화상병(fire blight) 및 과수검은가지마름병의 예방 또는 치료에 사용된다.
상술한 본 발명에 따른 농약 조성물은 과수화상병이 발생할 수 있는 과일들, 예를 들어, 사과, 배, 등에 이용될 수 있으나, 이에 한정되는 것은 아니며, 특히, 본 발명은 사과 또는 배의 장미과 식물의 과수화상병 및 과수검은가지마름병 방제에 효과적이다.
한편, 본 발명의 농약 조성물, 과수화상병 방제용 조성물, 에르위니아 아밀로보라(Erwinia amylovora) 및 에르위니아 파이리폴리아(Erwinia pyrifoliae) 증식 억제 또는 사멸용 조성물 중 선택되는 어느 하나는, 일종의 미생물 농약으로서, 액상, 분말상 등의 다양한 형태로 제조될 수 있다.
또한, 필요에 의해 미생물 농약에 사용되는 공지된 여러 부형제를 첨가할 수도 있는데, 상기 부형제는 미생물 농약에 사용되는 것을 특정의 것에 한정하지 않고 사용할 수 있으므로, 부형제에 관한 설명은 생략하기로 한다. 일례로, 본 본 발명에 따른 농약 조성물은 실제 포장에서 사용하기 적합한 안정적인 제제화를 목적으로 생화학 농약으로 사용가능한 계면활성제 또는 증량제 등을 부형제로 사용할 수 있다. 이 경우, 상기 농약 조성물은 수화제, 입상수화제, 액상수화제, 액제, 수용제, 수용성입제 및 캡슐화제로 이루어진 군에서 선택된 하나 이상의 형태로 제조될 수 있다.상기 계면활성제의 일예로 알킬(C8~C12)아릴설포네이트, 디알킬(C3~C6)아릴설포네이트, 디알킬(C8~C12)설포숙시네이트, 리그닌설포네이트, 나프탈렌설포네이트축합물, 나프탈렌설포네이트포르말린축합물, 알킬(C8~C12)나프탈렌설포네이트포르말린축합물, 폴리옥시에틸렌알킬(C8~C12)페닐설포네이트와 같은 설포네이트 화합물의 나트륨염 또는 칼슘염, 알킬(C8~C12)설페이트, 알킬(C8~C12)아릴설페이트, 폴리옥시에틸렌알킬(C8~C12)설페이트, 폴리옥시에틸렌알킬(C8~C12)페닐설페이트와 같은 설페이트 화합물의 나트륨염 또는 칼슘염, 폴리옥시알킬렌숙시네이트와 같은 숙시네이트화합물의 나트륨염 또는 칼슘염, 나트륨 벤조에이트, 알킬카르복실레이트 등의 음이온성 계면활성제, 폴리옥시에틸렌알킬(C8~C12)에테르, 폴리옥시에틸렌알킬(C8~C12)페닐에테르, 폴리옥시에틸렌알킬(C8~C12)페닐폴리머, 에틸렌옥사이드 프로필렌옥사이드 코폴리머와 같은 비이온성 계면활성제, 폴리카복실레이트, 트리톤 100 및 트윈 80으로 이루어진 군으로부터 선택되는 하나 또는 둘 이상이 혼합되어 사용될 수 있으며, 이들 이외의 다른 계면활성제들도 사용될 수 있음은 당해 기술분야에서 통상의 지식을 갖은 자에게는 용이하게 이해될 수 있을 것이다.
증량제로는 벤토나이트(bentonite), 활석, 클레이, 카올린, 탄산칼슘, 규사, 경석, 규조토, 산성 백토, 제올라이트, 펄라이트, 화이트 카본, 암모늄 설페이트, 요소, 포도당, 덱스트린(dextrin), 콩가루, 쌀, 밀, 황토, 포도당 및 전분, 물 등이 단독으로 또는 2종 이상 혼합되어 사용될 수 있으며, 이들 이외의 다른 증량제들도 사용될 수 있음은 당해 기술분야에서 통상의 지식을 갖은 자에게는 용이하게 이해될 수 있을 것이다.
본 발명은 상기 박테리오파지를 유효성분으로 포함하는 항생용 조성물을 제공한다.
본 발명은 상기 박테리오파지를 유효성분으로 포함하는, 에르위니아 아밀로보라 (Erwinia amylovora) 및 에르위니아 파이리폴리아(Erwinia pyrifoliae)에 의해 유발되는 질환의 예방 또는 치료용 조성물을 제공한다.
상기 박테리오파지를 유효성분으로 포함하는 상기 항생용 조성물, 예방 또는 치료용 조성물은 기존의 항균물질 또는 항생제에 비하여 약물 내성 또는 저항성을 유도하지 않아 안전하며, 에르위니아 아밀로보라 및 에르위니아 파이리폴리아에 대해 높은 특이성을 갖는다.
본 발명은 상기 박테리오파지를 유효성분으로 포함하는 소독제를 제공한다.
본 발명은 상기 박테리오파지를 유효성분으로 포함하는 세척제를 제공한다.
상기 박테리오파지를 유효성분으로 포함하는 상기 소독제 또는 세척제는 소독 또는 세척 효과가 뛰어나며, 에르위니아 아밀로보라 및 에르위니아 파이리폴리아에 대해 높은 특이성을 갖는다.
본 발명은 박테리오파지 Fifi067을 사용하여 과수화상병 또는 과수검은가지마름병을 방제하는 방법을 제공한다.
상기 과수화상병은 에르위니아 아밀로보라 (Erwinia amylovora)에 의해 유발되는 것으로, 상기 박테리오파지를 유효성분으로 포함하는 농약 조성물을 박테리아에 처리하여, 에르위니아 아밀로보라를 사멸시킬 수 있다.
상기 과수검은가지마름병은 에르위니아 파이리폴리아(Erwinia pyrifoliae)에 의해 유발되는 것으로, 상기 박테리오파지를 유효성분으로 포함하는 농약 조성물을 박테리아에 처리하여, 에르위니아 파이리폴리아를 사멸시킬 수 있다.
본 발명에 따른 박테리오파지를 이용한 방제(치료) 방법인 파지 테라피는 항생제 저항성 균주의 출현을 막고 환경에 영향을 끼치지 않아 안전하고 효과적인 과수화상병 및 과수검은가지마름병의 방제를 기대할 수 있다.
본 발명은 상기 박테리오파지의, 과수화상병(fire blight) 및 과수검은가지마름병으로 이루어진 군에서 선택된 하나 이상의 질병의 예방 또는 치료에 사용하기 위한 용도를 제공한다.
본 발명은 상기 박테리오파지의, 과수화상병(fire blight) 및 과수검은가지마름병으로 이루어진 군에서 선택된 하나 이상의 질병의 예방 또는 치료용 농약 조성물의 제조에 사용하기 위한 용도를 제공한다.
상기 박테리오파지, 과수화상병, 과수검은가지마름병, 예방, 치료, 농약 조성물 등에 관한 구체적인 내용은 상기한 바와 같거나 이를 준용할 수 있다.
본 명세서에 사용된 용어는 특정의 실시예를 기술하기 위한 것일 뿐, 첨부하는 특허청구의 범위에 의해서만 한정되는 본 발명의 범위를 한정하려는 것은 아님을 이해하여야 한다. 본 명세서에 사용되는 모든 기술용어 및 과학용어는 다른 언급이 없는 한은 기술적으로 통상의 기술을 가진 자에게 일반적으로 이해되는 것과 동일한 의미를 가진다.
본 명세서에서 어떤 부분이 어떤 구성요소를 "포함" 한다고 할 때, 이는 특별히 반대되는 기재가 없는 한 다른 구성요소를 제외하는 것이 아니라 다른 구성 요소를 더 포함할 수 있는 것을 의미한다.
한편, 본 발명의 여러 가지 구현예 및 실시예들은 명확한 반대의 지적이 없는 한 그 외의 어떤 다른 실시예들과 결합될 수 있다. 특히 바람직하거나 유리하다고 지시하는 어떤 특징도 바람직하거나 유리하다고 지시한 그 외의 어떤 특징 및 특징들과 결합될 수 있다.
본 명세서에 있어서, "박테리오파지(bacteriophage)"란 특정한 타겟 박테리아를 감염시키는 바이러스이다. 단백 질 캡시드(capsid)로 싸여 있는 박테리오파지의 머리는 핵산 게놈으로 이루어져 있으며, 몇몇 박테리오파지는 지질 또는 단백질로 구성된 꼬리를 갖는다. 대부분의 박테리오파지는 유전 물질로서 이중나선 DNA를 포함한다
본 명세서에서의 "농약"은 농작물의 보호와 생장에 사용되는 약제를 의미하며, 농작물의 재배 또는 저장 중 발생하는 병충, 해충, 잡초 등을 방제하는데 사용하는 화학농약 및 생물농약, 농작물의 생리기능을 증진 또는 억제하는데 사용되는 생장조정제, 약효를 증진시키는 보조제 등을 총칭한다.
본 명세서에 있어서, "방제"는 작물에 피해를 주는 각종 병해충을 예방하고 구제하는 것을 의미한다.
본 명세서에서의 "항생용 조성물"은 약제 형태로 동식물에게 제공되어 균을 사멸시킬 수 있는 제제를 의미하며, 방부제, 살균제, 항생제 및 항균제를 총칭하는 것이다.
본 명세서에서의 "항균제"는 미생물을 사멸시키거나 혹은 발육을 억제하는 물질을 의미하며, 방부제, 살균제 및 항생제를 총징하는 것이다.
본 명세서에서의 "소독제"는 병원 감염을 막기 위한 병원 및 보건용의 소독제로 유용하게 사용될 수 있고 일반 생활 소독제, 식품 및 조리 장소 및 설비의 소독제, 과수원 등의 건물, 축체, 음수, 깔짚, 난좌, 운반차량, 식기 등의 각종 생육 용품의 소독 등에 사용될 수 있다.
본 명세서에서의 "세척제"는 세정의 목적에 사용되는 약제를 의미한다.
본 발명에서 새롭게 분리된, 기탁번호 KACC 97038P인 박테리오파지는 에르위니아 아밀로보라(Erwinia amylovora) 및 에르위니아 파이리폴리아(Erwinia pyrifoliae)에 대한 특이적인 용균활성(사멸능)을 가진다. 다른 Erwinia 종에는 용균활성이 없어서 과수화상병균 및 과수검은가지마름병에 대한 특이도가 매우 높으며, 같은 에르위니아 아밀로보라 및 에르위니아 파이리폴리아 종내라면 모든 균주(strain)에 효과가 있기 때문에 균주-의존적이지 않다. 또한, 온도변화 또는 pH 변화에도 안정성이 높아서, 친환경적인 과수화상병 및 과수검은가지마름병 방제제로서 우수한 효과를 가진다.
도 1은 에르위니아 아밀로보라를 숙주로 하여 수행한 실험에서 본 발명의 박테리오파지가 플라크를 형성한 것이다.
도 2는 본 발명의 박테리오파지의 에르위니아 아밀로보라에 대한 용균활성을 확인한 것이다.
도 3은 본 발명의 박테리오파지를 투과전자현미경으로 확인한 것이다.
도 4는 온도에 따른 본 발명의 박테리오파지의 용균활성에 관한 것이다.
도 5는 pH에 따른 본 발명의 박테리오파지의 용균활성에 관한 것이다.
도 6은 유과에서의 과수화상병 방제 효과를 확인한 것이다.
도 7은 본 발명의 박테리오파지의 게놈 지도 (genome map)을 나타낸 도이다.
도 8은 본 발명의 박테리오파지의 계통수를 나타낸 도이다.
도 2는 본 발명의 박테리오파지의 에르위니아 아밀로보라에 대한 용균활성을 확인한 것이다.
도 3은 본 발명의 박테리오파지를 투과전자현미경으로 확인한 것이다.
도 4는 온도에 따른 본 발명의 박테리오파지의 용균활성에 관한 것이다.
도 5는 pH에 따른 본 발명의 박테리오파지의 용균활성에 관한 것이다.
도 6은 유과에서의 과수화상병 방제 효과를 확인한 것이다.
도 7은 본 발명의 박테리오파지의 게놈 지도 (genome map)을 나타낸 도이다.
도 8은 본 발명의 박테리오파지의 계통수를 나타낸 도이다.
이하 본 발명을 실시예 및 실험예를 통하여 보다 상세하게 설명한다. 그러나, 이들 실시예는 본 발명을 예시적으로 설명하기 위한 것으로 본 발명의 범위가 이들 실시예 및 실험예에 한정되는 것은 아니다.
실시예 및 실험예
실험예 1. 박테리오파지 분리
1.1. 박테리오파지 분리를 위한 환경 시료 전처리
박테리오파지의 분리를 위해 과수 화상병 발생 과수원(경기도 안성 서운면 배 과수원)과 인근의 토양과 물을 채집하였다. 토양 시료의 경우 10 g, 물 시료의 경우에는 10 ml을 50 ml conical tube에 담고 TSB(tryptic soy broth) 10 ml을 첨가한다. 여기에 24시간 진탕 배양한 과수 화상병균(Erwinia amylovora) 94 균주를 동일 비율로 섞은 혼합 배양액을 각각 1 ml 첨가하여 24시간 동안 진탕 배양하였다. 배양온도는 27이다. 배양된 시료는 10,000×g에서 5분간 원심분리하여 상층액만을 새로운 tube에 옮겨 담는다. 이렇게 얻어진 시료는 세균을 완전히 제거하기 위해 0.2 μm pore size filter로 여과하였다.
1.2. Dotting assay
박테리오파지의 증식을 유도를 위한 전치리를 마친 다양한 환경 시료에서 박테리오파지의 존재를 확인하기 위해 dotting assay를 수행하였다. TSB에 0.4% soft agar 첨가하여 멸균한 배지를 40 내지 50로 준비하였다. 배지 3ml에 밤새 진탕 배양한 과수 화상병균 1종을 15 μl 넣고 기포가 생기지 않게 섞은 후 TSA(tryptic soy agar)에 얇게 부어 10분간 굳힌다. 균주가 균일하게 포함된 배지 위에 여과한 환경 시료를 10μl씩 떨어뜨인 후 27에서 정치 배양한다. 여러 개의 환경 시료를 하나의 배지에 함께 떨어뜨릴 경우 시료가 서로 섞이지 않도록 충분한 간격을 유지하여야 한다. 24시간 배양 후 시료 부분에 세균이 자라지 못하고 투명하거나 플라크가 확인되면 양성으로 판정하였다.
1.3. Plaque assay(overlay assay)
박테리오파지를 순수분리하기 위해 overlay assay를 수행하였다. TSB에 0.4% soft agar 첨가하여 멸균한 배지를 40 내지 50로 준비한다. 배지 3 ml에 밤새 진탕 배양한 과수 화상병균 15 μl와 박테리오파지가 확인된 양성 시료를 10μl 넣고 기포가 생기지 않게 섞은 후 TSA에 얇게 부어 10분간 굳힌 후 27에서 24시간 동안 정치 배양한다. 이때 양성 시료는 단일 플라크를 얻기 위해 십진희석하여 농도별로 수행해야 한다. 24시간 배양 후 크기나 모양이 다른 플라크(plaque)를 선별하여 1 ml의 saline-magnesium(SM) buffer에 넣어 냉장 보관하였다. 각 플라크에서 추출한 박테리오파지는 단일 박테리오파지 분리를 위해 동일한 과정을 5번 이상 반복하였다. 이때 형성된 플라크(plaque)를 도 1에 나타내었다.
실험예 2. 용균활성 확인
과수 화상병균 (Erwinia amylovora YKB14808)을 TSB 배지에 전날 진탕 배양하여 준비한 뒤 24시간 후 재배양한다. 이후 세균의 농도가 OD600nm=0.5(108 CFU/ml)에 도달하게 되면 TSB 배지에 십진 희석하여 105 CFU/ml로 접종농도를 맞춰준다. 세균 배양액을 96-well plate에 180 μl씩 분주한 뒤 파지는 multiplicity of infection(MOI) 0.001, 0.1, 10, 1000에 맞춰 20 μl씩 접종한다. 이후 24시간 동안 마이크로플레이트 리더기에서 27, 120 rpm으로 진탕 배양하며 1시간 단위로 세균의 OD값을 측정한 것을 도 2에 나타내었다.
실험예 3. 형태학적 분석
박테리오파지의 증식을 위해 TSB 3 ml에 화상병균 (Erwinia amylovora YKB14808)을 24시간 진탕 배양한다. 24시간 진탕 배양한 화상병균 2 ml을 TSB 200 ml에 재배양한 후 OD600=0.5가 되면 108 PFU/ml 농도의 파지를 1 ml 처리한 후 24시간 진탕 배양한다. 24시간 진탕 배양한 시료의 불순물을 제거하기 위해 10,000×g에서 10분간 원심분리하여 상층액을 0.22 μm pore size filter로 여과하였다. 박테리오파지 시료에 Ployethylene glycol 8000(PEG 8000) 5g, 5 M NaCl 10ml을 처리한 후 4에서 24시간 배양한다. 24시간 배양한 시료를 9,000g에서 20분간 원심분리한 후 상층액을 제거하고 침전물을 SM buffer로 현탁하여 준비한다. 초고속원심분리용 튜브에 CsCl 밀도층(1.3 g/ml, 1.45 g/ml, 1.5 g/ml, 1.7 g/ml)을 역순으로 3 ml씩 쌓은 후 그 위에 농축된 파지 시료를 쌓고 785,500×g에서 2시간 동안 원심분리하여 정제된 파지를 얻었다. 정제된 파지를 SM buffer로 투석한 후 0.22 μm pore size filter로 여과하였다. 여과된 파지 시료를 2% uranyl acetate 용액으로 염색한 후 투과전자현미경을 통해 형태를 확인하여 도 3에 나타내었다.
실험예 4. 기주범위 분석
분리한 박테리오파지의 기주범위 분석은 Erwinia amylovora 94 균주, Erwinia pyrifoliae 25균주와 Dickeya zeae, Enterobacter cloacce, Escherichia coli, Pantoea agglomerans, Pectobacterium carotovorum, Pseudomonas fluoresceus, Xanthomonas campestris, Bacillus thuringieusis, Clavibacter michiganensis 및 Enterococcus faecalis를 사용하였다. 양성 대조군으로는 화상병균 방제용 박테리오파지 제제인 AgriPhage을, 음성 대조군으로는 SM buffer를 사용하였다. 기주범위 분석에는 dotting assay 방법을 이용하였으며 24시간 배양 후 플라크가 확인되면 양성으로 판정하였다. 구체적으로는, 투명환이 생성되는 경우를 +로, 그렇지 않은 경우를 -로 기재하여, 하기 표 1에 기재하였다. 모든 실험은 3번 내지 9번 반복으로 수행하고 관찰된 플라크의 단계점수의 평균값을 기록하였다.
No. | species | strain | Lytic activity of Erwinia phage Fifi067 |
1 | Erwinia amylovora | YKB 14715 | + |
2 | Erwinia amylovora | YKB 14740 | + |
3 | Erwinia amylovora | YKB 14742 | + |
4 | Erwinia amylovora | YKB 14748 | + |
5 | Erwinia amylovora | YKB 14750 | + |
6 | Erwinia amylovora | YKB 14754 | + |
7 | Erwinia amylovora | YKB 14756 | + |
8 | Erwinia amylovora | YKB 14758 | + |
9 | Erwinia amylovora | YKB 14768 | + |
10 | Erwinia amylovora | YKB 14770 | + |
11 | Erwinia amylovora | YKB 14776 | + |
12 | Erwinia amylovora | YKB 14778 | + |
13 | Erwinia amylovora | YKB 14787 | + |
14 | Erwinia amylovora | YKB 14806 | + |
15 | Erwinia amylovora | YKB 14808 | + |
16 | Erwinia amylovora | YKB 14814 | + |
17 | Erwinia amylovora | YKB 14818 | + |
18 | Erwinia amylovora | YKB 14820 | + |
19 | Erwinia amylovora | YKB 14822 | + |
20 | Erwinia amylovora | TS3128 | + |
21 | Erwinia amylovora | RA0023 | + |
22 | Erwinia amylovora | RA0024 | + |
23 | Erwinia amylovora | RA0025 | + |
24 | Erwinia amylovora | RA0026 | + |
25 | Erwinia amylovora | RA0027 | + |
26 | Erwinia amylovora | RA0028 | + |
27 | Erwinia amylovora | RA0029 | + |
28 | Erwinia amylovora | RA0030 | + |
29 | Erwinia amylovora | RA0031 | + |
30 | Erwinia amylovora | RA0032 | + |
31 | Erwinia amylovora | RA0033 | + |
32 | Erwinia amylovora | RA0034 | + |
33 | Erwinia amylovora | RA0035 | + |
34 | Erwinia amylovora | RA0036 | + |
35 | Erwinia amylovora | RA0037 | + |
36 | Erwinia amylovora | RA0038 | + |
37 | Erwinia amylovora | RA0039 | + |
38 | Erwinia amylovora | RA0040 | + |
39 | Erwinia amylovora | RA0041 | + |
40 | Erwinia amylovora | RA0042 | + |
41 | Erwinia amylovora | RA0043 | + |
42 | Erwinia amylovora | RA0044 | + |
43 | Erwinia amylovora | RA0045 | + |
44 | Erwinia amylovora | RA0046 | + |
45 | Erwinia amylovora | RA0047 | + |
46 | Erwinia amylovora | RA0048 | + |
47 | Erwinia amylovora | RA0049 | + |
48 | Erwinia amylovora | RA0050 | + |
49 | Erwinia amylovora | RA0051 | + |
50 | Erwinia amylovora | RA0052 | + |
51 | Erwinia amylovora | RA0053 | + |
52 | Erwinia amylovora | RA0054 | + |
53 | Erwinia amylovora | RA0055 | + |
54 | Erwinia amylovora | RA0056 | + |
55 | Erwinia amylovora | RA0057 | + |
56 | Erwinia amylovora | RA0058 | + |
57 | Erwinia amylovora | RA0059 | + |
58 | Erwinia amylovora | RA0060 | + |
59 | Erwinia amylovora | RA0061 | + |
60 | Erwinia amylovora | RA0062 | + |
61 | Erwinia amylovora | RA0063 | + |
62 | Erwinia amylovora | RA0064 | + |
63 | Erwinia amylovora | RA0065 | + |
64 | Erwinia amylovora | RA0066 | + |
65 | Erwinia amylovora | RA0067 | + |
66 | Erwinia amylovora | RA0068 | + |
67 | Erwinia amylovora | RA0069 | + |
68 | Erwinia amylovora | RA0070 | + |
69 | Erwinia amylovora | RA0071 | + |
70 | Erwinia amylovora | RA0072 | + |
71 | Erwinia amylovora | RA0073 | + |
72 | Erwinia amylovora | RA0074 | + |
73 | Erwinia amylovora | RA0075 | + |
74 | Erwinia amylovora | RA0076 | + |
75 | Erwinia amylovora | RA0077 | + |
76 | Erwinia amylovora | RA0078 | + |
77 | Erwinia amylovora | RA0079 | + |
78 | Erwinia amylovora | RA0080 | + |
79 | Erwinia amylovora | RA0081 | + |
80 | Erwinia amylovora | RA0082 | + |
81 | Erwinia amylovora | RA0083 | + |
82 | Erwinia amylovora | RA0084 | + |
83 | Erwinia amylovora | RA0085 | + |
84 | Erwinia amylovora | RA0086 | + |
85 | Erwinia amylovora | RA0087 | + |
86 | Erwinia amylovora | RA0088 | + |
87 | Erwinia amylovora | RA0089 | + |
88 | Erwinia amylovora | RA0090 | + |
89 | Erwinia amylovora | RA0091 | + |
90 | Erwinia amylovora | RA0092 | + |
91 | Erwinia amylovora | RA0093 | + |
92 | Erwinia amylovora | RA0094 | + |
93 | Erwinia amylovora | RA0095 | + |
94 | Erwinia amylovora | RA0096 | + |
95 | Erwinia pyrifoliae | Ep12327 | + |
96 | Erwinia pyrifoliae | RP0098 | + |
97 | Erwinia pyrifoliae | RP0099 | + |
98 | Erwinia pyrifoliae | RP0100 | + |
99 | Erwinia pyrifoliae | RP0101 | + |
100 | Erwinia pyrifoliae | RP0102 | + |
101 | Erwinia pyrifoliae | RP0103 | + |
102 | Erwinia pyrifoliae | RP0104 | + |
103 | Erwinia pyrifoliae | RP0105 | + |
104 | Erwinia pyrifoliae | RP0106 | + |
105 | Erwinia pyrifoliae | RP0107 | + |
106 | Erwinia pyrifoliae | RP0108 | + |
107 | Erwinia pyrifoliae | RP0109 | + |
108 | Erwinia pyrifoliae | RP0110 | + |
109 | Erwinia pyrifoliae | RP0111 | + |
110 | Erwinia pyrifoliae | RP0112 | + |
111 | Erwinia pyrifoliae | RP0113 | + |
112 | Erwinia pyrifoliae | RP0114 | + |
113 | Erwinia pyrifoliae | RP0115 | + |
114 | Erwinia pyrifoliae | RP0116 | + |
115 | Erwinia pyrifoliae | RP0117 | + |
116 | Erwinia pyrifoliae | RP0118 | + |
117 | Erwinia pyrifoliae | RP0119 | + |
118 | Erwinia pyrifoliae | RP0120 | + |
119 | Erwinia pyrifoliae | RP0121 | + |
120 | Dickeya zeae | - | |
121 | Enterobacter cloacce | - | |
123 | Escherichia coli | - | |
124 | Pantoea agglomerans | - | |
125 | Pectobacterium carotovorum | - | |
126 | Pseudomonas fluoresceus | - | |
127 | Xanthomonas campestris | - | |
128 | Bacillus thuringieusis | - | |
129 | Clavibacter michiganensis | - | |
130 | Enterococcus faecalis | - |
상기 표 1을 보면, 박테리오파지 Fifi067은 높은 에르위니아 아밀로보라 (Erwinia amylovora) 및 에르위니아 파이리폴리아(Erwinia pyrifoliae) 특이성을 가지고, 상기 균의 같은 종내라면 모든 균주(strain)에 효과가 있기 때문에 균주-의존적이지 않는 것을 알 수 있다.
실험예 5. 온도 및 pH 안정성
박테리오파지들의 다양한 온도와 pH에서의 활성 유지 여부를 확인하기 위해 안정성을 분석하였다. 각 파지의 농도는 105 PFU/ml을 사용하였다. 각 파지는 1.5 ml tube에 200 μl씩 분주한 후 30, 40, 50, 60에서 1시간 동안 처리하여 dotting assay를 통해 활성 농도의 변화를 확인하여 도 4에 나타내었다.
pH는 SM buffer에 HCl, NaOH를 이용하여 pH4 내지 11에 맞게 제조하였다. 각 pH에 맞게 제조된 SM buffer 990 μl에 107 PFU/ml 농도의 파지 10 μl을 1시간 동안 처리한 후 dotting assay를 통해 활성 농도의 변화를 확인하여 도 5에 나타내었다.
본 발명의 박테리오파지 Fifi067은 온도 변화 또는 pH 변화에도 안정성이 높아 친환경적인 과수화상병 및 과수검은가지마름병의 방제제로서 우수한 효과를 가짐을 알 수 있다.
실험예 6. 과수 화상병 발생 억제 효과 확인
과수 화상병균 (Erwinia amylovora YKB14808)을 TSB배지에 전날 진탕 배양하여 준비한다. 세균 배양액을 TSB 배지에 재배양하여 OD600nm=0.5 (108 CFU/ml)에 도달하면 1,800×g, 5분간 원심분리로 화상병균을 침전시키고 이후 Saline solution으로 씻어낸 뒤 10배 희석하여 세균 현탁액을 준비한다. 실험에 사용하는 미성숙과는 70% 에탄올로 표면 살균한다. 멸균된 1 mL 팁을 이용하여 미성숙과 표면에 구멍을 2개 뚫어준다. 미성숙과 표면에 만들어낸 구멍에 1010 PFU/ml의 파지 용액을 10 μl를 흐르지 않게 접종한다. 이후 파지 용액이 완전히 마르기 전에 107 CFU/ml의 세균 현탁액을 10 μl를 접종한 뒤 상대습도를 90% 이상으로 유지하고 27에서 약 2주간 2일 간격으로 병 발생 정도를 확인한 것을 도 6에 나타내었다. 도 6을 보면, 박테리오파지 Fifi067이 접종된 유과는 과수 화상병이 방제됨을 알 수 있다.
실험예 7. 염기서열 분석
박테리오파지 입자에 단백질 분해효소를 처리하여 외피를 제거하고 Norgen사의 phage DNA isolation kit를 사용하여 각 파지의 genomic DNA (gDNA)를 추출하였다. 100 내지 200 ng의 gDNA를 TruSeq Nano DNA kit를 사용하여 library를 제작 후, Illumina HiSeqXTen 플랫폼을 기반으로 염기서열 분석(next generation sequencing, NGS)을 수행하였다. 얻어진 전체 read는 단일 contig를 얻기위하여 assembly를 진행하였다. 서열분석으로 예측된 Open reading frame 각각의 기능을 Basic Local Alignment Search Tool (BLAST)와 HHpred을 이용하여 분석하였다. Erwinia phage Fifi067의 genome은 75,307bp의 크기를 가지며 92개의 open reading frame (ORFs) 및 7개의 tRNA가 예측되었다.
또한, 염기서열의 유전적 기능을 파악하기 위해 HHpred와 NCBI BLAST 프로그램을 이용해여 ORFs 분석을 실시하였으며 이를 BRIG를 이용하여 유전자 지도를 작성하였다 (표 2 및 도 7 참조).
Functional group | Locus tag | Predicted function |
Lysis | 67_00010 | Putative lysozyme |
67_00011 | putatiave spanin | |
67_00033 | Putative endonuclease | |
67_00049 | Putative rIIB | |
67_00050 | Putative rIIA | |
Structure | 67_00003 | Putative terminase, large subunit |
67_00012 | Putative portal | |
67_00015 | Putative major capsid protein | |
67_00041 | Putative tail fiber protein | |
67_00068 | Putative ATP dependent Clp protease | |
Nucleotide metabolism | 67_00021 | Putative virion DNA-directed RNA polymerase |
67_00037 | Putative exonuclease | |
67_00044 | Putative DNA polymerase | |
67_00046 | Putative ATP-dependent DNA helicase | |
67_00057 | Putative DNA adenine methyltransferase | |
67_00059 | Putative dCTP deaminase | |
67_00072 | Putative DNA dependent RNA polymerase | |
67_00074 | Putative T7 RNA polymerase | |
Additional function | 67_00006 | Putative cellulase |
67_00007 | Putative glycosyl hydrolase family 48 | |
67_00022 | Ca2+ release channel domain containing protein | |
67_00035 | AAA domain containing protein | |
67_00038 | Putative SaV protein | |
67_00047 | Putative phosphohydrolase | |
67_00048 | Putative transposase | |
67_00053 | Putative flavin dependent thymidylate synthase | |
67_00058 | Putative flagellar and swarming motility protein | |
67_00060 | Putative metallopeptidase | |
67_00077 | Macro domain_Poa1p family containing protein | |
hypothetical protein | 67_00001 | Hypothetical protein |
67_00002 | Hypothetical protein | |
67_00004 | Hypothetical protein | |
67_00005 | Hypothetical protein | |
67_00008 | Hypothetical protein | |
67_00009 | Hypothetical protein | |
67_00013 | Hypothetical protein | |
67_00014 | Hypothetical protein | |
67_00016 | Hypothetical protein | |
67_00017 | Hypothetical protein | |
67_00018 | Hypothetical protein | |
67_00019 | Hypothetical protein | |
67_00020 | Hypothetical protein | |
67_00030 | Hypothetical protein | |
67_00031 | Hypothetical protein | |
67_00032 | Hypothetical protein | |
67_00034 | Hypothetical protein | |
67_00036 | Hypothetical protein | |
67_00039 | Hypothetical protein | |
67_00040 | Hypothetical protein | |
67_00042 | Hypothetical protein | |
67_00043 | Hypothetical protein | |
67_00045 | Hypothetical protein | |
67_00051 | Hypothetical protein | |
67_00052 | Hypothetical protein | |
67_00054 | Hypothetical protein | |
67_00055 | Hypothetical protein | |
67_00056 | Hypothetical protein | |
67_00061 | Hypothetical protein | |
67_00062 | Hypothetical protein | |
67_00063 | Hypothetical protein | |
67_00064 | Hypothetical protein | |
67_00065 | Hypothetical protein | |
67_00066 | Hypothetical protein | |
67_00067 | Hypothetical protein | |
67_00069 | Hypothetical protein | |
67_00070 | Hypothetical protein | |
67_00071 | Hypothetical protein | |
67_00073 | Hypothetical protein | |
67_00075 | Hypothetical protein | |
67_00076 | Hypothetical protein | |
67_00078 | Hypothetical protein | |
67_00079 | Hypothetical protein | |
67_00080 | Hypothetical protein | |
67_00081 | Hypothetical protein | |
67_00082 | Hypothetical protein | |
67_00083 | Hypothetical protein | |
67_00084 | Hypothetical protein | |
67_00085 | Hypothetical protein | |
67_00086 | Hypothetical protein | |
67_00087 | Hypothetical protein | |
67_00088 | Hypothetical protein | |
67_00089 | Hypothetical protein | |
67_00090 | Hypothetical protein | |
67_00091 | Hypothetical protein | |
67_00092 | Hypothetical protein |
박테리오파지의 염기서열을 바탕으로 분석된 염기서열이 유전체상에서 어느 위치에 속하는지 개략적으로 알기 위해 Virus Classification and Tree Building Online Resouce (VICTOR)을 사용하여 계통수를 분석하였다 (도 8 참조).
<110> REPUBLIC OF KOREA(MANAGEMENT : RURAL DEVELOPMENT ADMINISTRATION)
<120> Novel bacteriophage specific for fire blight and black shoot
blight and use thereof
<130> PD22-023
<160> 1
<170> KoPatentIn 3.0
<210> 1
<211> 75307
<212> DNA
<213> Artificial Sequence
<220>
<223> Novel bacteriophage Fifi067
<400> 1
atgcgagacg agatgaagac atgatagaac tcctggttaa tatatgaatg caccattgca 60
tccagaccac gcgaagcgtg ggtgtatagt gtatgcagtt ggtgtaatta accggggggg 120
ggggataccc tcctcgcaag agtgctcgga gtgtaagata ctgaactaga acatacatat 180
gaaaaatatt ggcaatccga aatatattag aaataaatat attccctatg caaaaaagag 240
ggggaacaag tcccccaaag cgctatcaca cagttattct tcccagcttg atgaacctgt 300
ctgggcaggt gcagagtcag accccgtttt aattaatgag gcaaggagac ggcaatccct 360
ctactggttc cgtttaccca cggtttccta acggcatggc agcaagtcaa tgtctaaagc 420
atatcccatt cagtttatct tgttaagaac tatctgagca gaatactaag tgattgattt 480
atttgttgtt cttctcttgg ttccagtatt ggagccatag gggtagccct cctatcctat 540
ataagagtta ttgctttata tctaaagata ccctaaagtg caactgtcta tttacaggag 600
aagtccaaat gtctgaacgt attaatgaat tacttgaagc aagcccggcc ccacgagtga 660
ctgagcacca ggtgggtaat gaagcagtga caggtgagta tatcgtccgt ggttgtctga 720
cgatttgtat cctgaccctg aagaacgggt tcactgtggt gggcaccagt tcttgtgctg 780
caccggagaa cttcaacgaa gagattggtc gccactttgc actgaaagat gcagagcgtc 840
aggtctggcc tttactgggc ttccgtctga aagacaagct gcacgctgaa caggaagcca 900
atgacctggt atctggtctt aatgaaggcg actgcgaagg ctgcaaaatt taagtttaat 960
aggtgggggt agaaataccc cctcaacata tattagaggt agcccatgct aaccagagaa 1020
attgtagaga aagcactgcc tgctacgttg aaaggtgctg tcactcctga actgattgcc 1080
aagctgaata gcgtgacaat ggatcaagtg gtagccgagc aggtgcgtga taacttcatc 1140
tcctatactg gcgtgctgcg tgaagggaag ttccgtactg aggactacct caatgcagta 1200
accttcgtca gctatcggtt gatgaaccat accaataaag atgcttatat caagacgttc 1260
cctgaccgtt atcaggattt gctgatggca ggccgttctg ataaggacat ctcagcctac 1320
gtttctgcgt atgcgaagaa caaactggtg aacctgattc tggaacagag tctggtgcca 1380
agctgggtgc tcaatcagga cttgttccaa aaagccctta acacccaggc agagattatg 1440
aatgaccata acgtgttggc ccgtgaccgt gtggcagcag ccaactccat tctgactcat 1500
ctgcaaaaac cgaaagaggc cgggccactt gtgaacatcg acatgcgtga aaactcaggc 1560
atgaacgaac tcaaagccac cctttcttcc ttggctcaag agcagcgtag gctgatcggt 1620
cagggtgtga ctgccaaaga cattgttggc agaagtatct ttgagaacca ggaggaataa 1680
tggcactcgt tcagcaagag ctagaccaat ggcttgacca ggtagattat tcatacctga 1740
actcggctca gtacattccg tctgagtttg ctctgctgtt tgctgccttt attaagctgg 1800
tgaacggtga tgcaggtgag tcacacaaga caccacctgt tcaccttgcc atgttggaca 1860
aagtagtaag cagtaactcg gactacattg ctaacctttg tttccgtgga gcagcaaaaa 1920
caacactgtt tatggaatac ttctgtctct ttattgcctg cttcggttat ctcgaaggtc 1980
tgggcaagat tgacggtatg atctacgtat ctgactcaat ggataacggt gttaagtctg 2040
cacgtaagaa cattgagttc cgttacaaca acagtgagtt cctgcaagag tggattccag 2100
aagctaagtt cactgacaac taccttgagt ttaagaacaa agaaggccac atgctcggcg 2160
tcaagatgtt tggtgccaag acaggtcttc gtggtacgaa gattttcggt aaacgtccgg 2220
tactctgtgt gctcgatgac ttgatcagtg atgacgactc caaatccaag gtgtcgatgg 2280
atgcgatcaa ggacaccgta tataaaggtg tgaaccacgc actcgatcca actcgccgta 2340
aggtcatctt taacggtact ccgtttaata aagacgacat cttgattgaa gcagtcgagt 2400
ctggtgcatg ggatgtcaac gtgtggcctg tgtgcgagcg tttcccttgc tcagaagaag 2460
agttctgtgg tgcatgggaa gaccgtttct catacaagta cgtgaaagag cagtacgaga 2520
tggcagtgaa gacaggtaaa gtcgctggct tcatgcagga actgatgctt cgcattactt 2580
ctgaggaaga acgccttgta caagaggctg atattcgctg gtacagtaag gccaagctgt 2640
taaacagcaa gcatctgtac aactattaca tcaccactga ctttgccacc agcaagaaac 2700
agtctgctga cttctcagtt atctttgtct gggcgtataa cgccaacggt gactggttgt 2760
gggtagatgg tgttgttgaa cggcagcaga tggacaagaa tattgatgac cttttccgtc 2820
tggttcagat ttacaaccca caagcagttg gtgtggaagt caccgggcaa caaaatgcct 2880
tcatccagtg gcttcagaaa gaaatgatcg accgtaatgt ctggtttaac ttcgcctcaa 2940
gctcaaaaac tggggaacca ggaataagac ctgacactga caaactctct cgcttcaacc 3000
ttgtcgttcc ttggttcaag gctgggaaat tctattaccc aatggagatg aaagagtcca 3060
agatcattgg catctatcat ggtcagttac gccttgctac ccaatcgggc ctaaaaggta 3120
aagatgactg tatcgacggg acatcccagc tcgcatactt caaaccgtgg aaaccatcgg 3180
caggtatgaa tagtggtgaa gtcactgtag acccgtgggg tgatgacgac gataatagca 3240
ctggggtaaa tgcccttgat aattacatcg tgtgaggcga tatgaacctg gaaaacctgt 3300
atcagacgct ctcatatggt caactcagta accttgccat ctcagcagat ggctctggga 3360
cgatcattga gtcgggccag cccaagattg tgatcgctgc taacgaggca ttgaaacgcc 3420
tgtacagtaa gttcaatctg ctggaaaaag atgtgctgat cgagcaagca tcacacatta 3480
ctaactacca tttggacaaa cgctttgcag aatcctcata cgatcctgac aaagttaatt 3540
ttccatatat caaggacttg tttaatgagc cgtttgaaga tgatgtgatt cgtatcacgg 3600
gtgttttcaa cagccataac aactatcctt tgcctctgaa cgacgatgaa gcagagtggt 3660
cacttttcac tccacgctac aacattcttc aggtgccgaa gccacaggat aaggtatcat 3720
tgagtgtaat gtaccaggcc aagcatccac ctctggatgt ggaacgacct gagcaagaga 3780
tcatcttgcc agatgttctc gaaggtgcgt ttactgcatt cattgccttc cacatttaca 3840
acaacatgaa cacgcaggaa agccaattga aggcagtagg ccacttgcag gtgcatgatc 3900
gcatcgtgca agaggttatg gataacgatc tggttaactc cagcatctca acgaccaatg 3960
ctcggttcga aaaaagagga tggaagtaat gaatatgcga gccactcatg atccttacaa 4020
cgatggagca caactcgttg ataagatgat cggtaatgcc taccaggtag tgaagttcgt 4080
tgccatgaac atgaagttca tcaagcacgt atcagcacaa ctggaagctg tctataacgt 4140
gtcgtcaaat atgactgcac tgctgcaagt ttcagaggtt acgcctcaga ttgctattct 4200
ggctccactg tctgctgaga ttaaaatcct cggtgacaat gctgccaagc tgatcagtct 4260
ggcgaacaac cttgatgcag ttattgctgt gcaacagaac ctggtggcac tgaatcgtgt 4320
gtctgccaac atcaatgatg tgacttctgt gtccaccaac atggctgctg tgcttgcggt 4380
taatgctggt ctgcctgcga ttgaagtaat tcagtcgaaa ctgccaatgc tgcaaggtat 4440
tgctgacaag atggatgagc tggacgatat ttctgcccag ttgccagcta ttcaggccat 4500
caataccaac atgacagcac tgctggcact ggaagctgac ctggatactc tgaacggtat 4560
ctatgctgac ctggcgaaca tcaacagtgt tgctgcttcc attgcaaacg ttaatgcagt 4620
cgctgccgat ctcaccaaaa tcaatgcagt tcaggctgat ttggcgaaca tcgacgcagt 4680
tgcaggtaag ctgactgaga tcgacgcagt gaatactgct ctgcctcaac tgactgctct 4740
gcaattgcag tcaaccaaga cggcaacgat gggtgcagta ggcacttcga ccaatgtggc 4800
actgggcact atcgactcaa ccaaagtgac gagcatttct gcttctatcc ttggttctga 4860
cggtgtgcgt tacttcccgg atggtacgaa tttcgtcgtc accatgacca caaccaacat 4920
cgtgctgaca ctgaatgcgt ctgcccctgc tgctattgca ggtggtgctg caacagtgct 4980
catttcatac cattcataag ggtaagctga tggctaagaa accctacctg ggtctgaaat 5040
actacgagtt tgctgatcag tacagcagcc gtatcattaa cccacgcaaa tggcctaaag 5100
gtgagctggg gatgatctat cccaatgagt tcacctttgg cactgtgtcg gttggcaatg 5160
cttccaacca acagactgca attctgaaga atgaaggtct gcaacctctg ccgatcaagt 5220
caatcactgt tgttggtgat tacctggtgg agactgatgc accaattgaa ggctatctgg 5280
acgttggtaa gtctgcccag atcaagatta ccttcgtgcc taagcgttcc ggtctgttga 5340
cgggtggtgt gtacgttgat actggcgatg cagcaggtca ggagttcatc tccatgatgg 5400
gctacggtac aggcggttca tcaactggta ttactgctac gccgaccagt ctttcctttg 5460
gttccgtggc tatcaaccag gcatcaacag cgaagactgt ggtgatcggt aacactggta 5520
ctgatgacat taccctgaac tctgtgacaa ccacaggcat gttctctgtc agtgcaagtc 5580
tgccgaaaac tctggcccca ggcgatacgg ttactctgtc cgtaacgttc cgtccgacta 5640
gtgttggaac caagacagga aacatcgctc tgaatcacaa cggtactggt gtcactgaca 5700
tcgcactgac tggtacaggc accgatggtt ctactggccc aactatcaac gtcactgacg 5760
gtgttttgga gactgtaacc gatagttctt ctgttactgc ctcggcaacc tcgttgtctt 5820
ttaattcagt ggtgatcggt aattcaggta cgggcaccat tgtcttatcc aactcaggag 5880
gcaaggatgc ttccatctta acctgcgttg taactggtac agggttcgcc ctgtccagcg 5940
attctgccaa agccgggaca gttattccgg ctggcagttc tgttcaggtc aaaatggtga 6000
tgacaccaac tgctgaaggt gattatgcag gtgatttgca tatcactacc aatgctgatg 6060
taggcactga ctttgctgtt tccctttctg gttccggggt aacggaagtt atcgtactgg 6120
atcggctgac agtcagtggt gtcaagattg tgaagaccgg gacaacgact caggttagac 6180
tgaagtccgt taactggttc ggtatggaag gtacgaacta cactccacat ggaacctggt 6240
cacaaccttg gaaaaatatc attgatgaca ttgccagcat gggcttcaac tgcattcgct 6300
tcccgtttag tggcgacact actactgctg ggcgtactcc accttcgacg gctatcgacg 6360
aaacggctaa ccctgatctt gttggactga gttcgttagc aatcctcgat ttgtacatcg 6420
actactgcac gcagaagggg atctatgttg ttcttgatca ccatcgtcgt tctgctgggg 6480
atggtgctga cggttctcct attgacggct cttataccct ccaaaactgg aaggactcgt 6540
gggctgtcat ggcgaatcgc tatggcacta acactactgt tgttggtgct gacgtacata 6600
acgagcctca tgaccttacc tggtctgtgt gggctggata tgtggagcag tgtgctgcaa 6660
ctattcacgc gattgcctct gattggctga tcttcgtgga aggtgtgggt acaaacagtg 6720
atggcaccgc atattggtgg ggtggtgctc tgaaggacgt tgcaacccgt cctatctcgt 6780
tgtctgtggc aaaccgtgtg gtgtattcac cgcatgagta cggtcaatcg gttggatctc 6840
aaacctggtt gtctaccgac tccacaccag tggcgaatta ccctaacaac cttccggctg 6900
tatgggatgc taactggggc tttatccata aaaatggaat tgctcctatc tgggtaggtg 6960
agtttggtgg taaatttggg gtagacggat ctggtaatgc aaatcagcca aatggcaccg 7020
tcgagaagca atgggtatcg actcttgcca cttacctcaa ccaaaccaca ccgatgaact 7080
tcgcctattg gggatataac ccgaatagtt cggatacggg tggattggta caggatgact 7140
gggtaacaca ccagactgtt aaactaaatc tgttagctcc actgctgact taatgaagga 7200
atcaggcgat gcgtcaagca cgattcacaa tctcgcttag tgctgcatct actggaactg 7260
taactgtggg ttatgcaact gtcgatggaa cggcagttgc aggaactgac tatacggcaa 7320
ccagtggcac agcgaccttt gaaccaggag agacaagtaa agatgtcctg gttcctgttc 7380
gtgattatca ggaaggcatt ggctccctgg cattcaccct tgcactgtct actccgtcag 7440
gcggtacact gggtacgaaa accagcggta gtctgactat tccaggtgat ccggcagttc 7500
tgccttctta tctggatcgt ttccacaccg tttatacggc tgtgcataac gtaaataatg 7560
gatactttgg gcctccgact ggtgctgctg cacacaccat gccgtaccac tgtatcgaaa 7620
cgctgatttg tgaagctcca gactggggac acgaaacagt atccgaaaca gcttcattct 7680
acgttggtct ggaagcgtgg aaaggtctgc tggacaatga ctggactggc ttcaataaag 7740
catggaacac gatcagtaca atctatgttc ctaacactac gaatcaacct ttacagactt 7800
acaatgctgg gcatcctgct gattacactc cagaaggtga tactcctaac gcataccctg 7860
tacttggtga tagcactgct gctgtgggta ttgacccgtt gtatgacgaa ttgcttacga 7920
cttatggtaa taagcagatg tttctcatgc actggatcat tgacgttgat ggggcttacg 7980
gtttcaaaaa tggtgacggt tctaagctaa acgtctatat caacaactac caacgtggtc 8040
tgcaagagtc tgcctgggaa actattaccc agccagagtg ggaagacttc acctacggtt 8100
cgacttatgg attcctgcct ctcttccaac agggcttgcc tgtctacgaa gaagcagaaa 8160
acgagtacgg tactcagtgg cgttatacct ctgcaccgga tgctgaagct cgtgcaattc 8220
aatggtcgtt ctgggcgaac aagtgggcca ctgccaatgg taaagctggt gaggtagcaa 8280
cctcatacaa ctatgccaag aaaatgggtg actatctgcg ttactgcttg tttgacaagt 8340
atttccgtca gatcggtact aaccgtgctc agggttcaac tactgctgca ccgtacactg 8400
cctgccacta tctgatctca tggtatattt catggggtgg tcagattccg gtagatggtg 8460
aaggttactg gggcttccgt attggttcat ctgaatcaca cttcggttat caggcaccgg 8520
acatcgctta cttcatggca actggtggtg gtggtatgac tccactgtct gcgtctgctg 8580
gtgacatctg gcttggttct atgtacaagc agcttgagat gatccgttgg ttgcaaaccc 8640
tggaaggccc gattgctggt ggtgtttcta actcctggaa aggccgttat gaaactccga 8700
atgatggtcg tgataatttc acattctacg ggatgtatta cacgtatgcc ccggtatggc 8760
atgatccacc atcgaacaac tggttcggtt tccaggcatg gggcttaggc cgtgttgcag 8820
atctgatgct ggaagtggct tctgttgagt cgccatctac catgcagacc aacgtctaca 8880
acatgtgtga aacgatcctc gaccgcttct gtaactggtg tgtaaacaac attaccatga 8940
atacagaatc actggacttc actctgccag atacactgaa ctggacttct ccaactcagg 9000
tgttgggtga gactaccaac agcccgaacc tggaaggagt gtacgaatac attccgtcta 9060
ctaagtggga tggtactggt gacagcactg ctttctggga tccagcgagt gtgcctaacc 9120
cgttactgaa gttccgcatt gtggcatcgg gtaaagacct tggtgttgct tcttctctgg 9180
ctctgctgat gctgcactat gcaaaagcga aacgagttaa gaataagttc gatacagcaa 9240
tgctggcatc cgacaccaat acgccaaatg atgtttataa actggcgaaa aacctggtag 9300
atggtatgtg gtcgttgtac tggaacggtg tgggtatcgc tcgtgaggaa gctcgttctg 9360
actataacaa gtacaaccaa cagttgtatg tgccaaacaa ctacactggc tatatgccaa 9420
acggtgatgt gatcaactcc agttcgacgt ttatctctat ccgttcatgg cagaaagctg 9480
atgcagactg gcctaaaatc caggcatact tggattccca gaccgaaagt acgattccta 9540
agttcacgta ccaccgtttc tgggcacaat gtgagtacgc tatgtgttgc ggggctttgc 9600
atcaatactt tagtgacata aactaagccc gtccgggtag ttaaattgag aagccagggg 9660
acatcctctg gcttcttttt tgtatagatg gggaagcaaa agatgagtaa tgagtctgtg 9720
gatgtccaac ttgcaaggat tgatgagcgt atgaaaacga tcatcttggg ccttgaacag 9780
gatcgcattt ccagaaaaga acagtacgaa actacagagc agatccgtct gacaattcag 9840
gatattcaga atcgagtcgg tgctgttgaa aaggggctgg ctgatagtgc cccaaccatc 9900
gaagagttca ttaccatcaa gcacaaagtt gctggtgctg gtgtagctgg tcggtggctc 9960
tgggtagcag cagcagcaat tcttggtttc ctctttacca tgcgtaggga aattatcgaa 10020
tggctcgcaa agtgaagtta gtagataact ggaaacgagc acataagttc gcttcaatct 10080
ggtggactgt agcgggtatt gttgccatga tttttgaaat cctcaacaat acctggttca 10140
gtcttcctca agagatccaa aacaaaatcc ccaatgcttc ttacgtcagc ctggcactat 10200
tcattgctat cgccattgct cgcgtaattc agtgggtaaa gccggagaat aacgatgcca 10260
gtgagtagca ctactaagaa ggttggtggt gttggtactg tggctgctgc gataatcgca 10320
gcagttttcg cagttgaggg tggatactcc aatgatcctc aagaccctgg tggggaaacc 10380
aaccacggta ttaccaaaac cgttgcagtg caaaatggtt atacgggtga catgaaagtc 10440
atgacccaga accaggctgc tgatatttat ttccgtgatt acatccagaa acctggatat 10500
gaaccaatgc ttacagtatc acccaccgtc tccatgaaac tggtagatgc tgctgtaaac 10560
gctgggcctg gtcgttcttc tctctggttc cagactgcca tcaatgccta taacaatgac 10620
ggcaaatctt tccctcaaat taatgttgat ggtaaagtag gtgcaggtac aatcaacgcc 10680
tataagtcac tgcaaaatgt tcgtggaaaa gtgaaggctt gtgaactgat gatcaaggca 10740
ttggatgccc aacaagccag ctactacatg agcctcacta agctgaagaa atacacagtc 10800
ggttggatgg ataaccggat cggcaatgta ccaatcagca aatgccagga agatgctaaa 10860
tgagtgtact gaccattcag gctaaagcag tggtaggtct tgttgctatc ggcttgttgg 10920
caggttcttt cttctggttc tatgagaaag ggaagtctca tggtgaagac aatattcaaa 10980
ccaagtggaa ccaagaaaag aatctccagg ctactgccat gaatttactg aaggatcagt 11040
atgcagttct ggaagctgcc aaccggaaga agactgagga tttaacccat gaccttgcac 11100
aagcacaaca aactcacgca ctcgctatgg ctagtgctca gtctgacttt gataagcggt 11160
tgctccagtc caacaaaaga gcagacttat ataaacgtca aaccgaaact ggaaccactg 11220
aatgcagagc tatcgcaagc catgcagccg aactcgacag aagtcttgaa gaaggccgat 11280
cagtggtcgc tgaactctca gcaactctta gactccgtga tagtcaactg attgcactgg 11340
gtgctaaact tttggcagat cgtcaactaa tcacaggtgt agataatgga tcaacagatt 11400
cagcaacgac caagtgaaga taacgtaagt tacattactg actggcctaa agagccttca 11460
gtacgtacct tgaagctgga tcttgaggca gcacgtcctt cgcatgatgc acaaaatcag 11520
aagatcgatc attggaacga tctgatgaat gtccagaaca gcgtgaaacc gaagaaggtt 11580
aaaggccgtt ccagcgtaca gccaaagctc attcgccgtc aggctgaatg gcgttactca 11640
gccttgtctg aaccgttcct gtccaccaat aaaatgttca acgtcacacc tgtgtcgttc 11700
gaagatgtat ccggtgcagt gcagaaccag ttgctgatca actggcagtt cagaaccaag 11760
ctgaacaagg taaagctgat cgatgactac gttcgttccg tggtcgatga aggcacgtcc 11820
attactaaag tgggctggtt gcgtgaaacc aaaaaggtta agcagcaagt tcctgtctgg 11880
gcgtattatc caatccagga tcagcaatca ctgatggctt tccaacaggc tatgcagtta 11940
cgcgaagaaa accctcgtgg atttaacgaa ggtgatccag cactgaaagc tgctgttgag 12000
ttcttcgatg aaacccaaca accaacggtt gctgtgcaaa ctggcaccga agaggtggag 12060
gttgatcagg tagttgtgaa ccagccaacc atcgacgtgc tggatccaaa caacgtctat 12120
gttgatccat cgtgcaacgg tgacttgaac aaagcactgt tcgtcatcct ggcattcgaa 12180
accaataaag ctgaactgtc caaataccca gaccgttaca gcaatttgga tcgtgttgac 12240
tggaaaaaca acagcccgac tacccagacc aattacacca ctaccacacc acaggacttc 12300
acctttgctg atgaactccg ttccaaagta gtggcgtatg aatactgggg ttatgctgac 12360
atcaacgatg acggctcact cgttccgatt gttgccacct ggattggtga tgtaatgatc 12420
cgtatggagc tgaacccgta cccggatgag aagctgcctt ttgttctggt tccatatctg 12480
ccgaagaaac gtgacttgtt tggtgagcca gatgcagaac tgctggaaga taaccaggcg 12540
atcctgggtg ctactacccg tggcatcatc gatcttctcg gacgttcagc caatgctcaa 12600
cagggctttg ccaaaggtat gctcgatccg gtcaaccgta agaagtatga agacggtaaa 12660
gactacgagt ttaaccaagc tcagaacccg gcacagaaca tgatccagca taagttccct 12720
gagattcctc agtcggctat gcaggtattg cagatgcaga accaggaagc agaatccctt 12780
accggggtga aagcctttgc tggtggcgta tcgggtaatg cctatggcga tgttgctgct 12840
ggtatccgtg gtgcattgga tgctgcatca aaacgtgaga tggctattct tcgtcgtctg 12900
gcaaaaggca tgacagagat cggcaccaag atcattgcca tgaatgctgc cttcctgtca 12960
gagactgaag ttgtccgtgt cactaatgac aaatttgtca cgattaaccg tgaagatctg 13020
aaaggtaact atgatctgga agtggacatt tccactgctg aagttgatga ccagaaatct 13080
tctgatctgg gctttatgat ccagactatc ggcccggtac tggaagaccc gactgttacc 13140
actcgtctgc tttccgagat tgccacgttg aaacgtatgc cagaactagc acactatctg 13200
ctgacctggc aacctaagcc tgatccgttc aaagaacaga tgcaacaatt gcagcttcaa 13260
cagcaacaac tggaaaacca gaaactgcaa tctgagatcg agaaaaacca ggctcttgct 13320
gcacaagcac gtagtaattc tgataaaacc aacctcgact ttgttgagca ggaatcaggt 13380
actaaacatg ctcgtgatat ggagaaacag aaaggccagg ccgaaggtaa tcagcaactg 13440
gaagttacca aagcattact caagactcag aagaaacctg atggtgctga gactagacca 13500
gatgtgactg ctgctattgg ttataatgca ctcactaatg gagataactt gaataatgct 13560
ggacagagcc aaccagctca aactaatatt acgccagacg ttgcagccga aaaccctagc 13620
caaaacattg gttcagctca gtttcagcca cagcgagatc cagccctaaa cccttctatt 13680
ggtatttgag gaaagttaaa acatgacaca aatcgaagct cttgagcagc aattgagcga 13740
ttcacgactc cttatcgagc accgtgatat gattctcaaa ctctcaggta atcgtgagtt 13800
ccgtaaggta attctcgaag gattctgtga gaaagagtgt gctcgttatg cccgtcaatc 13860
tggcgaccca atgctgtctg caactgaacg tgcagatgct ctggcaatgg ctcaggccgc 13920
aggccacctg aaacgcttct tgtccattca ggttcagatc ggcaacactg cccacaacac 13980
tatcccagac atcgagatgc aactcgacga actgcgtgcc agtcctgaag aagaagaagg 14040
tgacgaataa tggaaaatcc ggctgctgaa acccagccgg acatctctaa gatgtccgac 14100
gatgaaatcc tggcaatgga ctcattccct tctgcacctg ttgatgccgc agctccttct 14160
tctggttccc aagaggaaca aactcagcaa gaagaagttg ttcagcctca gcagactgat 14220
gtagaagagg aagagtctac tgttgaacaa caacagtcta ctgaagaagt tgatcagaat 14280
actggcaaag atcctgtaaa ggatgctaaa gttgctgaca acaaagtaga caacaccgat 14340
ccaacagcgg ctacttctgg taaagagact cagactaata ctgaacaaac tcagacccag 14400
aaggataaca agcctgctga tggtgaaatt gactacaagg catttcacga gacgattctc 14460
aaacccttca aagctaatgg caagatggtt gcccctaaag atgcagccga agctatccag 14520
cttatgcaga tgggtgcgaa ctacactcgt aaaatgcagg acttagctcc gtatcgtaaa 14580
gctgggttga tgcttgagaa cgtgggctta ctcgatgaga caaaacttag ttacctgatt 14640
gatctccata acaaggatcc gcaggcgatt aagaagctca ttgaagactc cggttacgat 14700
gttcacgaac acgacccgga tgtaaaatcg acctatacac ctaacggcaa tcacactgtt 14760
agtgacgatc aggttgcgtt taaggctgtc ttggatgatg tagcatcatc tgagggtggt 14820
cgtgagacgc tccacgagat caacactaaa tgggatcaag ccagtaaaga tctcctgttt 14880
actaacccgg aaatcgcagc gacgattcat tctcaacgtg aatctggtgt ataccagaaa 14940
atcacagccg agattgagca catgcgtact cttggtcaga ttggtgcgag tgtgcctttc 15000
ttgcaagcct accgtgcggt tggcgataaa ctgcaagcag caggtgcatt taatccagta 15060
ccacaacagg aagctgaaaa gcctgcccca gttgcagtgc gtgcggcaaa accaaaacca 15120
caggtagaca actctgcaca agcggctgct gcggcatcca ctcgtactgg gggtaaacct 15180
gccaaacctc aaccgaactt tgctgtttcg gatgaagagt tcatgaagca gtttgaaaac 15240
cgttaaggat agatagatgc tcaattataa cgccccagca gacggtcaaa agtctagcat 15300
tgatggtgct ggctccgacc agatgaatac tttcttctgg ctgaagaaag cgatcatcac 15360
cgctcgtaaa gagcagttct ttatgccgtt ggctaacgtg accaacatgc cgaagaacta 15420
cggtaaaacc atgaagctgt acgaatacgt gcctcttctg gatgaccgta acatcaacga 15480
ccagggtatt gacgctaatg gcgtaaccat tgcgaacggc aacctgtacg gttcaagccg 15540
tgacatcggt actatcacct ctcgtctgcc aacgctgact gagaacggtg gtcgtgttaa 15600
ccgtgtcggc ttcacccgtc tggagcgtga aggttcactg cacaagttcg gtttcttcca 15660
tgagttcacc caagagtcat tcgacttcga ctctgacgat ggtctgaagg atcacctggc 15720
tcgtgaactg gtaactggtg ctgtccagtt gaccgaagct gttctgcaaa aagacctgct 15780
ggctgctact ggtgtaatcc tgtatgcagg tgctgcggtt tctgacgatg aaatcactgg 15840
tgaagcatca actactggcg gtgttaccac tccagcttca gttgtgacct accagaacat 15900
catgcgtctg gatcagatcc tgaccgacaa ccgtactcca accagtacca ctatcatcac 15960
tggttctcgt ttcatcgaca ccaaagtgat cggtgcgacc cgtgtgatgt acgttggttc 16020
tgagctggtg ccactgctga aaggtctgcg tgacctgttc aatgaaaaag cattcattga 16080
aatccagcac tatggcgatg cgggtactct gatgaacggt gaagtcggtt ctatcgacaa 16140
gttccgtatc atccaggttc ctgaaatgct gcactgggct gctgctggtg ctgaagcgac 16200
tgatgagaat ccgggctacc gtacctcaac tgacgcttct ggtactgagc gttataacgt 16260
gtacccaatg ctggttgttg gtgatgatgc gtttaccact atcggcttcc agtcgaatgg 16320
taagactgcg aacttcacca tcatgaccaa gatgccaggt ctggaaactg ctgaccgtaa 16380
cgatccgttc ggtgagactg gtttcagctc aatcaagtgg tactacggta tcctggttaa 16440
gcgtcctgag cgtctggctc agatcaaaac ggttgcaccg ctgtaataag caacctatat 16500
tagaggggag ccgaaaggct ccctttttta ttaccaacaa cttaatagga cacgccaatg 16560
agcacccttg aaaacggtca gaacgacgag agtaccgtta atgaaaacgc cgaacagatg 16620
gaaaaacaac gccgtcagct tttgatgggc cgtgcccgta tgatgggtct gtctttctcc 16680
aacaacattg ctaccgaaaa gctgtctaag atgatcgaag ctgcaatgga aggaaagtca 16740
ctggaaccag agaagaaagc tgaggctcct gaactcaatc cgctggacgg tgacgctgct 16800
ggtaagaaac ctgcgaaagc caaatccctg cgtcagcaac tgtatgacaa acaaatgcgg 16860
ttggtgcgtc tgcgtatcac ctgtatggat ccaaagaaaa aagacctgcc tggtgaaatc 16920
ttcactattg ccaatgaaca tctcggtact gtccgtaagt ttgttccatt tggcgaagta 16980
accgatgaag gttatcatgt gccgtactgc atctataaga tgctggaagc acgtcagttc 17040
ttgaacgtgc gtaccatcaa agatcgccgt accaagacta cccgtgtaga aactacctgg 17100
gtcagagagt ttgctctgga agttatgccc ccactgacac ctgcacagat tcaggatctg 17160
aagactgctc agttagcagc gggtatgtaa ccactacggt aaacaagatg gcccttagat 17220
gggccatttt tatttgagga ttatcatgag cacatataac gtcgagacag aagcccaggc 17280
agtgtacaca gcactgactg ctgactttga ctttaatctg cctgacatca accttgacga 17340
cccccaatac caattcccat atgatcctga ctcactgctg tataaggaca ttgagcctgt 17400
aacagtagag atgttgacct ctggatcagt ggacggtact ggtgtgtttg atgtgctgat 17460
gaaagcagtc aaaggccatc tgcgtatgga gtatgatgct ggtcgtatta tgggtgccga 17520
atataccaag gcttatattg gctcggtaca ggctacccta cagaatgcga ctcagttcct 17580
gctcggtaaa gaccaggcat tctggcaagc tcaggctgca cagattgctg cgatcactgg 17640
cattacccaa ctggcaacag ccaagatgca gtttgctgca actcgtctgg aagctgctaa 17700
tcagggtgca gcatatgctc tgaccaaagc acgtctgggt actgaatcag tccaatacgg 17760
cactgctgtt ttcaacctgt ctaccatgtt gcctgcacag aaaacctctg tggatctggc 17820
taacgacttg gctactcaga acatcaagac ggctggtgtg cagtacagca ctgctgctta 17880
taatctgtct cagatgcttc ctgctcagta cagcaacctg actcaacaga ctgcgatgat 17940
tggtcgtcag attacgatga tcactgaaca gactgaaacg taccgtgctc agactctgga 18000
cactcgtacc gatggtcaga ctgtggctgg ttcggttggt aagcagaaag ctctgtacac 18060
tcaacagatc acatcgtacc tgcgtaacga tgagcgttct gctgccaaga tcttctctga 18120
tgtgtggaca gcaatgaaaa ccattgatga aggtctgact gccccgactg cattcaccaa 18180
tgacagcatc aatgctgtta tgcagactgt tatcaccaac aacgatctag gctaaaaaca 18240
atgggcttct tcaaggctaa gaaaaagatt tacgtatcgt catctgtcta caatctggca 18300
ggtggtgacg aagatcgtgt gaactatctc aagactgttg tggtgggtaa ggtcattgct 18360
gacactgctc cttcgacagg acttggtgaa gcgatcacta atagctactt gaatggccca 18420
ggtttgaagc tcagaagttt tggtaagtgg gctgtgaact ccgggtacaa cgctatgctg 18480
ggtatgcaat ccggtacgtt gtatctcgga gattccattg atgatgaagc tctgaaaccg 18540
tttctgcctg ttcctcctgg ttccactgct gtacttcagt cggcagaaat tgaccttgca 18600
gattacacct ggtgggctga ccaatatatt gttcagaacc accctgaatt actcaatact 18660
gattatgcca gtgactatga tgagagcact ggaatcatca ctattaacta tgcagatggt 18720
acgtctgaga cgtttacacc aactgattac gacactgcat ccaagtacct gtatgcagcc 18780
tattttgttt cttctgggga tgagactggc ccactggtgc ccggtactcc ggtaactctg 18840
ggggcgactg atccattccc gtctactgat ggttggacgg tggataagtc atcctctgtg 18900
actaccagct ataacctgct gaaacagact gacgtggtga tctcttatag tgacggtcgt 18960
cctgatgaga catcccatgc tgaatccacc acagtggaaa cggccccagt tattgataat 19020
gagtaccata aatcagagtt ccagggtgcc tcttcttctg gttccaatca ggtcagtacc 19080
actgagaact cattccgtta tgactaccaa accaaccagg ttgtagacaa tgatccagaa 19140
gagacaacga gcacggagac tttaccggat ggtacaatca aaaccacaac gaccacgatt 19200
aaaacgcaaa gcgttgaacg tagccgtggg tatcgcattg acactcagac tgtcacaagc 19260
actctgtcat cgtccaatgt cttcatctac aaatatggct ctggtaactc aaccctggat 19320
gccatgttcg cagctaacgc ttcagtcggt ggcttcttgc cattcatccc agtcagaata 19380
gataacgaca tgatcgacga taatcgtttt gacgattact acccgttgat cgagaaagcg 19440
tataagaaat ctgttcgagc aaagttcact gaactgatcg ataaggtgaa agacaatgaa 19500
agcattggtg acattgatta tgcctactgc gtatttggtg tctcacttaa tgtaaaagac 19560
aatgcctgtc gtaagtacgt ttatacgttc tttgaaaacc tgttggactc ggtgggtaat 19620
gacccggcct atgccaatta ccgtactgca atggctgctg cttcagccag taatcaggct 19680
tttgctgcat ggtctgctgc acagtcggat ccaagtaatc cgctgtatgg cacacctcaa 19740
ccttcggtac tgtcttatcc ttctctgcct acacaaggtg tgcaggtgaa gagtaatggc 19800
ctgatgaact tcaacatgat catcaactgg tcaaatctgg cgaagaccat tggcacaggc 19860
atgaaagaca gcactcacaa tgtgggtgat tgctggtttg aaattggtac ggatgacaac 19920
tatgagcaga tcattttcaa cggctcaacg tctgccagta actcgttctc agtgaaccac 19980
attattatct acaagcagga ctcagctaca gcatggtctg ctatgcacgt atatggttta 20040
cggcatatca acaagatcta cggtggtaag tcagtagata ctgatggtaa agatgcgatt 20100
aatgactctg aggaatcagg gttcattatc ccagtacagc gtgacattct gacttccttc 20160
tctttgaagg atgcaaccca gatggctact gcctgtaaca tcatggtgtt caactgctat 20220
caggttgtta agcagaaatg gtatcagact tcctggttca aggtagtgct ggtggttatt 20280
gtcattatcg tctcgatctt cactgctggt gcaggagccg gggcaggtgc tggtctgtta 20340
ggtacggctg catcggttgg tgctgctgtt ggtctaacgg gtgtggcagc aatcatcgtg 20400
ggtacaattg ctaatgcctt agcagcaatg ctgctgatga agctgatcgg tgttgctgcc 20460
actgctctgt ttggtgagaa gtacggtgcc atcgttggtg cagtagcctc tgtaattgca 20520
gtggctgtcg ggacttcata tgcaaacggt ggtagtattt cagccgggtt ctcttccctt 20580
accagagcag agaacatcat ccgactgaca gaagctgctg gtaatggcta tgctcaatac 20640
atgcaggctg ctgtaaatga aaccatcaaa gagactcagg aagttcttga taattatcag 20700
gacaagatga aagacattgc tgagaagtac aacgatatgt ttggtactga ctcaacaggt 20760
tacattgatc ccctgaagat tactgaagcg accaacatga tgttggaaag tcaggacagc 20820
ttccttagcc gtacaatgat gagtggtgaa gatattgcaa atctgtccct cggactgatt 20880
accaacttca ctgatattat gatctcaaca gaccttccgg ggtgattaaa tgagcgatat 20940
gggtctttat aacagtggtg ttgtgccgaa ctacggctac aacaacccta acctaaatat 21000
catgggcaac aacggtgtat ctgctgctgg tggtaatgga ttctcattct ccaacaaccc 21060
caacagtgca ttgaactatc agccaggtca acaagctaca gcactgaaca ataccaatat 21120
tgctggtgct gatcagactg gttcatttgg tgatacgctg ggcatgaaca ttccaacctt 21180
ccagttggga ctgtccggtc tgagtaccgt tggtaatctg tatggtgcat tccaggctaa 21240
caagctggcg aactcgcagt tcgattacac caaaaagatt actgatacca atctggcgaa 21300
ctcgatcaag tcgtataaca ctacgctttc tgatcgtgct gctgctcgtg gttccgtgga 21360
aggttggtct gatgctcaga cttccgacta cgttaataag aataaactgt aaggaacaat 21420
catggcccag attacttggc gtaatgtgga tgctccttct ttctctggtt cgctggacgg 21480
tcttcgtgta gctgggcagt tcatgaataa tgcaacaggt gccttgagtg atggcctgaa 21540
agcatttgga caagcccagc aacaacgtgc cgatgctgct gccattggga actcacttca 21600
atattcagat ccggctgcgt accaagctgc tttggcagac ggttcgctgc tcaatggtat 21660
tgaccgttct caggtgtctg ctcagacgtt gggtgctctg gctgatcgtt caggccagtt 21720
gatcaacaat gctgggaacc aacagaaaca ggacattctt ggttatggtt tcgaccgtac 21780
ccagactcag aatcagaaca ctgatgctgc ccgtaatgtt attggtcaga tttacactgc 21840
ccagcaacag ggtgatcagg gtgctgttaa tcgtctgctc cagcaaaatg ctggtgtgct 21900
cggtcaactg tcaccagaag aacaagccaa cctgtacaaa actggtggtg atgttgcagg 21960
ccaacgccta aacaacattg gtcaggcact ggggaaccaa ggaagaagta tcgggaatgc 22020
agatgctgcc ctgtcactga atcagcgtca gcttggtatc aatgaccaga atcaggtagc 22080
ccaggtactg aatactgtat ccggttctgt attgcctggt gacaatgatg gtgcccgtgc 22140
aattgccgaa ggtgccatga aaaacctgtc accacagggg cagatgctgc tgcgttcttc 22200
tctgggtcag caattccctg gtgtgtacag ttctccggct ggtggtttag gtggtgcaac 22260
cgttatgact ggtggcaagc aaatgcctgc tggttatgac actttgggtg ctgtcgtcga 22320
tggtaagtct gatctgctga agtacaatcc gcaaggtacg gcttctggta actatcagat 22380
cactgctgat acttatgcag agtttggccc gaaagcattg ggtgcaaact ggcgtagtgc 22440
gaacccacag gatccagttg ttcaggatgc tgtaggccag gaaatctgga actcggttaa 22500
agatgatcca tcgaagattc agggtcgttg ggcttcgttt actccggcac aggcagaagc 22560
tgccaaaggt aaatcatggg ctgatgtccg tgggactatt gctcaggcag agtcctctac 22620
tcctgcgtcc cagcttcctc ctttggttca gccatcggct caacagaatc aggcaacagc 22680
tctggcactg gataacaacc agcgtactgt tcgtgctggt cagaacacag cacagcaaca 22740
gtggatggac acacttctgc aaacgcaaag tgatacttcc acctcagcca gtgatgcaac 22800
tgacagcctg ctgaaaggcg cattcaaagg tactaaccgt ggctacctgc tgaacacagt 22860
aaaccgtgtt gtgcagcaag ctggtgttac ccctgcgact gctgcccgta tgctggagtc 22920
aaacgtggaa gacagtaaca atatcttcca acgtgcaggt catgctgtcc gtactcttgg 22980
tggtctggtt cgtaacgatg aaagcacacc tgatctgggt caaggtatcc gtatcaatga 23040
tgacggtctg aacaacgcaa ttcagttgca gcgttctggt tctactcagc aaacactgat 23100
gaaccaacgt gatctgcaag tacagggtgc agcaagtaag caggccaatg atgctctggt 23160
acaagcccag aacaactaca ataacctgct tcgtcgtatc ccaagtcagc cgggtctgca 23220
atcacagttg cctcgttatc aggctgctct ggatgctgca acggcgaact ttaaacaggt 23280
ggttgggccg tctctgacaa accagaacaa cgccccattg gtgaacggtc agcctaaccc 23340
taatctgatg ccagttgctc aacctgctcc ggtggcaacc tctacgggaa gcccacgagc 23400
acagcctgcg gatcagcctg ctgctccaac aggtaacttc aaccagcaac tgctcgatac 23460
ttacggcaga ctgcgaggtt aagtgctttt ctgaatcaaa agccctatca taacggtagg 23520
gctttttctt tggctccaca tggtgtaaat tacctcaaac atatatcgta aaggaatcag 23580
taatgtcatc tattaatgat attctgtcgc agtacgcttc tagcccagcg cctcaagatc 23640
cagcccctac gggtatctcc caaatcgtac agagtacggt tgcctcagtc tcacctgata 23700
aacaagcaca agtcgctaac gcatcgaacc agaagaaaca ggatctgggg atgtcgcctg 23760
ccgataatta caatgctctg tacggtcaga tgaacggtgt tggtaatgct tctgcatccc 23820
aacaggaaca ggatcagcgt aacctctcac caggtcagta catggtgaag tacggtgtgg 23880
atgcttataa ccagttcgct gctggtcagg ccgaagcgtc tcgatcaatc actgccgatg 23940
taaatgctgc tcataacact gacggtgtga acacaatcac tgacggtatt cagggtgtag 24000
gccaaggtct tgttaactct gttgtcggta ttggtgccct cggtgctggc ctcgttgatc 24060
gtgatgctgg acagtctctc agtaactcac tgaaccagtt caacgacaac gtaaacgcca 24120
acaaatctga ctctcagcaa gctggtcagc gtctggttag tgctctgaat atgaacactg 24180
aacgtgacaa tgaagcccag tacaaacaag atgtgaagga tgatggatct cttattgcag 24240
gtcttaaaaa cattggtcgt ggtgctgttg attctgtctc caacactctc agtaatcctg 24300
ctgcattgct tgatggtacg gctcaaggtg ttggctccct tctaactgct ggcccaatgt 24360
ctaaagctct ccgtgcaatt ggatcggctg ttattccaca ggctactcgc cgtggcgtag 24420
cactggctgc tgcattggat actgctgccg gaactcgctc tgctgcaaca ctggcaatgg 24480
gtgctgctga acatgcccct attcttggct caatcggcct gatggaagct ggtggtactt 24540
accaacagac gaactctgac atctctcaga tgccattcga tgaactggct aaacagtcac 24600
ctcagttcaa tgaactggtt aaaggtggta tgagccagga agatgcacgt tctgagatcg 24660
ccaaccgttc tggtctgttg gctgctgcta ttcagttccc tgttgctgct gcaactggtt 24720
cactggtcag taagtttgaa gccaatccgt ttgctgctaa aggcgttcgt actctgcttc 24780
agaactctgg taaagagact ctggaagaag gtgtgcaatc agctaccagc caattggcaa 24840
ccaactatgc agaacagcaa gaagccttgc ctaacaaaga gatcagccaa ggtgttggtc 24900
agcaattggg tcaaggtgct ctgttcggtc tgacctcaac tggtgttgtt tccggcccag 24960
gttctgttgc tgcttctgct gtacgtgctc cagttgacgc tgctaaagct gcatacgcac 25020
tgggcaaccg tgctgtggac gctgcgaaga actctgagct gctgtggaat gcaaacactg 25080
ccgtacaagc tgctgccgat caggttaagt ctgtcgtcaa acctggtatt gactggctgg 25140
ctaaacgtgg tgatgaagcc taccgtaaga tgcaggaaag ctcccctgta tctgatgcga 25200
acatggaaac cactgcccgt gacgtactca acaacgcacc ggaaaacctg caagctgcga 25260
aagaggccgt tgagcaaacc aatgtctccc ctgaagagaa ggctgctact aacgactacc 25320
tcgattctct ttctggttcc ctggactttg tggctgatga ttatgctgga actcctgact 25380
acgtacaaaa aaccgtagaa ggatcaagca accagatcga agctatgcag aagatggctg 25440
cgttcgttaa cgatgagaag aactctccac aagagcgttt catgacaggt tctattctgt 25500
cagcgatcat caatggctca caggatctgg taaaccagaa ctcgtctgca ctggcaaact 25560
tgccagccga tcaccctgca taccagtttg ctgctggcat tgaagatctg cacgcttctt 25620
tcgagaagtc acagggtctg tctaaagcac aggctgcaat ggataacatg gcaaacaatg 25680
ctcagacgta tgacattgtg aaaccagttg atgcagatac gattgctacc ccagaaggtc 25740
agcaaaacgt ggaagcacag gtggcattgg cgactgttgc tccagataag atcaatccag 25800
aagatgcgaa gatcattctg caacaagcga agaatggtgc aatcactctg aacaacaagc 25860
aatccgctgc tctgaacgtt gctatttctt tggttcaaag tgccagagag tacgcagaac 25920
aatctcagcg tgaaggctgg tctaagtcag acaagactgc gtattctctg aaggctgctg 25980
atgatgaggg ttcagcccaa ccgtcagttc tggttatggc tcgccgcatt tatgcgtctt 26040
acgctgcggg tgatctcgac ggggccagag attctcttga tcatctgatg caacttgccg 26100
tacatatgaa cggtaaggtt tccactatta acacgcacct tactgacgtt gcgaacccta 26160
acggcaataa cgcactcaac tatctccagc tccagcccga ccgtacctgg aagatgacga 26220
ctggcaaaga tactgtcggg gtcactccaa cctctcccgg ttcggtgaag tttgctcgtc 26280
gtgtagctgg cgaagcccaa tttgttacga acgtagcgaa tggcctggct caggcgttca 26340
gtgatttggg tgttagttcc attgaccata caaacctcga tactcgtttg tctgaaggca 26400
ctaccaaaca aacagcacag gacttccgcg atggtgttcg tgtggcaggc aaaagtgata 26460
cagctcctgt acagactgta gctgctgaag acactccagc acaacagacg caggataaac 26520
aaactgtaag cgaagcggat aataccactc aagcagaaca gtctgatgct caatttgttc 26580
caggtgatga agtgatctgg gcgaataaag atcatgacct gccagtgact taccgtggtc 26640
aggacgaagt tgggcctgat ggtcagacgt attctgtcgt ggcttatcag ggcaaacctt 26700
cctatgttct gaaaagtgaa ctgcgtgcta aaactgagtc tgctccagtg caggaagcaa 26760
caactgtgcc agttgtggaa ccagaacaga aagctgctcc tacaactgtg acagaagcat 26820
atgacaaact gaatgtgccg gacggtggga agaactattt ccactctgca ttcactttgc 26880
ctaagactca gcgttcacgt acccagggtg tagaaaaccc actggctgta ttgaactctg 26940
ctctggcaag tgatgaagac ttgcattctt tctctggttc agaaagcagt aatcacctga 27000
ctccagaagt gtcttctgct tatcagggta tgatgcaata tgctaaaggc atcgtgcaga 27060
acctgaataa aatcctgcgt gacgacatcg ctgcacagat caaatctggc aaaccatatc 27120
tggtgccgga taatgctgct gcgtacaaat cactggaagg taagtcattc aacatcgttg 27180
agactctgcc taatggtgtg gttcgctata accctgagct gattcagaat gctgtgttag 27240
ctggtatcca gtgggcactg acttcataca accaaggtgc aaacctggat gtggaagaca 27300
ttgcgaagat ccttggcact gagccgggtg agattgatgc tgatatgtat gctgctttca 27360
acacttcaat gaccactgct gaagcactgc gtactctgtc tgacaagatc ggtaaatact 27420
ggggtctgtc tgagaacaag aacgactatg acggtttcgt caaagggatt cctgcctcag 27480
ttgcttcaga gatcatgcgt gcatttgagc aagctggcct ggttgaaacc actactcaga 27540
acttcacagt tactgatgca gagggcaacg tacagccacg taagatcgac ttcactgctc 27600
tgaagctgga cgataccgaa gacagcaaac aactcaccaa tacgctgatg cagtatccgt 27660
ctgcgattga tgatgccgtg ctggttgaac cagaagagaa acgttacaca ggtgatgagc 27720
gtcctccgat tgctcgtact cagatgcgta atgcagaggt gcgtaatacc cctgagcaaa 27780
tcgccgtgct gaagaatgtg cagaacactc cataccgttt acacatgcca atggtcagcc 27840
tgctgaactt cattggtcgt gacggtgttc gtgatctgtt cggtgaaggt gatctggaaa 27900
gcaaggctct gaacgtcaac gataagaaag gtaaagaagg ccgtaacgct tcctacacca 27960
atgcgtttga cgagctgact aaattgcaga tggatctcaa taaccgtctg gtcgatgaag 28020
atggtgatat tggtcagact gacatcttct acgcttacaa cttctctcgt gtaaaccgtt 28080
tgcagatgct gggtcgttac aacccacaag ccagcaagtt gatgcgtgaa gctgttctgc 28140
caacccatac cactgtggat atggctgatg ctgatcaacg tatgggcttt gaccttggcc 28200
ttgctcaggc attgggtatc aagatccaca acatgcctca tgctgattca gtggaactgc 28260
tgaacaaact gttaaacggt aaactggctc ctgccattgc tgttatgcag gagttccaca 28320
gcactgatgc tctgcctgat tcaggtgtgg aaacactgcg taatgctggt gtggattccc 28380
ctgtcgctct gcaagcagtc agtgaatatg ctcgcttcct gaaccaggaa ggaaacaaca 28440
ctttcaacac cccgatgtat gtcgaggctg atggtgtgac caacggtatt gccaacgcaa 28500
cgcagatgct gtcatctggt ggatttacta ctgactacta tgtgaactcg caacgtactg 28560
gcctcttctt tggttctgag cacactaccc tgaacactta ccgtcaacag gataagactg 28620
acctgtatgg tgcaacgggt actgatctga ctactggcct gaatagcctg aagaagaacc 28680
tgcaaggcaa gccagatgtg gcagtacagt tgaacagtct gcaaggtctg atgaacatgt 28740
tcctgccggg tgctgttctg gatgatcagg gcaacctgaa cattgaccgt ggtgtcacca 28800
agaaccctct gacaattact gtctatggtt caagtgcctt cggtattgct ggtaacatca 28860
ctgatgccat cgtgaatgag atctatgcca aaatgtctga ggctgctcag gcacaggcca 28920
acgatccttc tctgagcttt gctaaagcaa tgttcggtaa agatggtcag caacagttcg 28980
atgatctgca acagtacatc aatgacctga ccacaactga agcccgttgg agtcctaaac 29040
gtaacgagta tttcactcag gcagtaagca ctgagtctgg tgacttctct tctccgcagg 29100
catttacctt ctcaactgag gaacgtaatg ctatccgtgc gaatgtgaac tcactgttta 29160
ttcgtccgat gactgactca atcaccaaga ctgttggcag ttctgttatg cagaacatga 29220
ccgatattcg tcaggcgact caggcaatct ccatcttcca ggagaatgct ttccgtcagg 29280
cagtggctga agaacaggaa ctggcattag cagcagacag caactacaag aagcactacc 29340
tgttgccaca gaacactcag aaccagatcc ttaaatctgt cactgagacg ttcccgatga 29400
tctctactgg tgcccagacg ttctttatcg gtggatctaa taacggttac tcaaccaata 29460
gttctattgg tcgtgcccgt gatggttcgt accgtagcac tgcaaccatg tatggcccac 29520
aggattccgg cgtagctggt gctgcatacc tgaacattgg tatgggcgat gctcgcatga 29580
ttcaggttgg ctttactggt cgtgacagtg tgaagcgtgc tctgccagtg ttcgatggtg 29640
tgaacctgcc gattgatcgc ctgtctcgtg acagcctgaa actgaatggt gctgtgttcg 29700
aatcgtggaa ccagaaccca gtggatgctg tgctgaagtc actgaatacc agtctgaaga 29760
atgccgatgc agtggacatg acaccggaaa tggttaagca gatgtctcgt gctctgactg 29820
gtgatcgtga catgcttacc accaaagacg aagtgattcg tgagctgaag tacattgctg 29880
accgtatggc tactaccagc aagtcgattg atgctcgtca taaaactctg cgtcagttca 29940
acctgcatat tgaccagatg gcatcaatgg ctgcttctta ccaaaacgtt ggtgagcaac 30000
tgcctaacga tcctgctcag gccgtggccc gaatgaatca ggtctatagc cagaacatga 30060
aaggtgtagt agcagaagcc ccggtgaaac aggaaggtaa accagcaacc acagttggcg 30120
tttcttctcc tggttccaag gctcgtgtca tctcaatgaa caagctgagt ggtctggtga 30180
aatctctgga actgactggc gttaagaaag caatgttcga cgaaattcgt cgctctgctg 30240
ctgccaaagg ttacaagatc atcactggta gccgtgaaga actgctggca tataacgaag 30300
ccaacggtaa cactcatccg gctaacgagt tcaccaatct ggcgaatgac ggtttcattt 30360
caccgtctac taaagagatc tacatcaaca atgcaactgc tcaaacgctg ctgcatgaga 30420
tggttcacgc ctccactttc gagactgtgc ttgatcacta tcaaggcaac accactcctg 30480
agattactca gtcagtgtct gccattgaag ggatgctggg acagtttatg aatctggatg 30540
ctttctctct ggatccaaaa actcgtattg attacgaaaa tgccaaggct gctgtcaacg 30600
gttgggcgac caacggtgat gtgtccgaag cacaacgtca ggctggagca ctgaacgagt 30660
tcatggcttg gtcactggct acaggctccc tgaataaggt attggagaaa accccgatcc 30720
tgaaacagat tactgatgct gtgttcaatg cgatccgtaa gattgtatac ggtcgtaaac 30780
gcatcccagc gacaccaggc gacgatattc tgtcaaacct gatgttccat actggtgtga 30840
tcgtgcgtgg gcaggcgagc gtacagaacg tctctggtga cactaagctg taccagtctc 30900
gtgtgtatgg taacagtgcc cgtctggaag aactgaacaa gacttttgat gctgtcgtga 30960
ctgcacatat caatgaagca cctgatatgt cagtgaagtc caaacgtcag accgaagctg 31020
ctcaggcact gatcaacggt aacgatgtgg cctattcgtt catgaaccac ggcttcccga 31080
tgaacatgca acaggctaca accttcagca tgatagtctc ggctctggcg acacaggctc 31140
atattgatcc ggcgtcaatg aattatgccc aggagctgta tgaccatgtg atcgataagc 31200
tggacttggg ccacttcctg ccgaatgccc cgtggacgca gcaggaagaa tatgatgcga 31260
ctgagaagta caacagcatc atgggtcgtt acatccagac caaagacagc aaaggtcgtt 31320
cgtctctgct gcctgctttc ctggctctgg caatgactga tgacggtttc cgtgctgtgc 31380
tgaatgatat tggcctgccg gagaaccaga aaggaaatgg cactctggat ggtaacatcg 31440
aagcgttcgg cactaacatg ctggattcac tcggtcgccg tatggctggt gatactcagt 31500
ctgagaatgt ccgtgctgct gttgacgcac tgactgatcg gatcatggac actgctgcca 31560
accgtgagac gtttatcgat cagtatgctg gcccactggg tagcattgtt gaccgtgcta 31620
acgagattgt ttccgatggt ctgactgctc tgtctgatac cttgtgggac ggtgccgata 31680
aagtgaaggc acataccaac aacaaaacta tcactgcact ggctgatgca accaagatgt 31740
ttgcagcaat cgccagcgaa gagaaagcag gtatcgtggc agaaggtgtg agcactgtga 31800
tcaacaacct gccgggtatg caggcaatgc gtgatgttat cggtgatatt gttggtcgta 31860
cttcaaccaa caaagatgtc tacgatctga tcaagcgttt ccgtactgct atccagcaag 31920
accgtcaaca gttccgtgac gtactgcctg gcattattgc tcagaagttc tcaactgaac 31980
tgactgatga tcagtggtca gcaatgcacc atgctcttgc gaagacagat attgtctccc 32040
tgttccagca ctttaatgct gatgagatcc acgctctgat gcaggatggt cgtactctgc 32100
gtggcaagat cactgcgttt gaaaaccgca ttgatgcgaa tgcctcgaag atgcacgctg 32160
gcctgatcaa gaagaaagca cagcaactgg ctcacttcat gatgggtggt gaaccgggca 32220
agaacctgct gcgtaatgct gaggcaattg gtcgtctgct cggtgagaca gacaaggctt 32280
actcttctac cactgacatg gtgaaagaca ttgatggcct gacttctctg tatgccatcg 32340
agcaactgac tcgtgctcag aaagatgccg tcttctctct ggttcagaaa gaagcctctg 32400
gtatggactt tgttatgtcc tacctgaaag gtcaacgtgc tgaggaacag cgtaagctgc 32460
gtgataatcc tcgtgccaag ttcaatggtt acaaaggtta tgtgccagaa gtgcgtgatc 32520
cgggcgttac cctgatcgtt gctgaggact cagaatctgc caagctggag agcatgagcc 32580
tgaagcgtat tggtgattac cagggtagct ctgctgaacc aggtaaagtg aaacgtggct 32640
attacttcgg taacgtccag tctcgcacta tgttcaacca gggtctgatg cagaacgttc 32700
gccagacagg taacggtgtg gataccaatt acggtttcac tcaggatgca ctggctggac 32760
gtatcactga tcgcacgact gtgaaatcaa tcactgctcg tctgaaagct ggtgagacag 32820
gacaaaacct gctgccagtg tacgacgacc gtggtcaggt tgtggcgtat gagcgttctc 32880
tggatcggaa cattcaggcc aagaccagcc catctgatca ccttgctaag atgatcggtg 32940
tgtggcgtgg tcgtcaggtt gaagagatca aaggtgctga gtacaacaag gtgctgatcg 33000
atactctcca cgacatgtac cagaacgaga ctaaaggcac tccttctaaa gaggccgagt 33060
atgtcaacgt gctggcagac aaccttgatc cggtgctggc tgatgctgtg aaactgatgc 33120
cgaaagaagt ccgtgattat gcacagtctg tgttcggtga tggcttctac gtccgtaagg 33180
atctgctgaa tgacaccttt ggctatcgtg aggcaaccat tggtgacgca tggactggta 33240
acgctcgctg gagtcctgag actctctcta cagccaagcg tgtggcaatg ggtatctttg 33300
gtgctgaagc gtatcgcaac ttcaccaagg ctgaatcaat gctgcaaaac tttgttcagg 33360
atgcacgtac cctgatcatc gttaagtcag tgattgttcc attcgctaac gccgtagcca 33420
acgtattgca gttggttggt cgtggtgtgc caatgaaaga tgtggtgcgt ggtgttccac 33480
gtaagctggc tgagatcaac acttatgtga agactcgtgc tctcgaagtt gaggcagaag 33540
ccgacctgcg tgcagcagag aatgatccaa gggaacaacg ccgactgcaa tccaagattc 33600
agggattcca ggacagctat cgccgtatgt caatctggcc tctgctggaa gctggtgagt 33660
tctcagctat ccacgatgcc tcagtgggtg acaccattga actgacttca ggccgtatta 33720
acagcttcat ggagcagcaa gtggataagc tgcctaagtc gctgcaaacg gctggtcgtt 33780
acgctctggt aacgaaagac actgccttgt tcaaggcact ggagaagtca gtggagtacg 33840
gtgactttgt ggcgaaggcc attctgtatg atgacattgt tcgtcgccag aagaagcctg 33900
tggcaaatgg actggctgct gtgaccgaag agtttgtgaa ctatgatcga ctgccaggtc 33960
gtttccgtgg atacatggag aagactgggc tactctggtt ctataactat aaggttcgtt 34020
ccgtgaaggt ggcattgtcc actatccgaa acaacccggt acatgctctg ttagcagcga 34080
acctgccact gccggatatg ttcgggaaca tcggtagccc tatcaccgat aacctgatca 34140
ctcagatggc agacggtgga ctgaattact cagtcggtat gggacaagca ttccatgctc 34200
cgttccttaa cccttgggtt aacctcgctc actaaccaat taaaaaagcc ctctttcgag 34260
ggctttcttt tttacgcaat actacttgaa ggcatgtacc acagcacgga acaggaagtc 34320
tttgaccttt tgctcaggtg gtaattcgtc aaatggaacc agacaaggat gggtcttggc 34380
ctcaggatct ttcacttctc cgtacaccca gccagtatcc agcttctctt tcatccacga 34440
ctcgtggctg gcagatggtg ggaaatcacc ggacatatgc agttccacac ctttcagtgc 34500
agactggact tgccacagtg gggcatcgtc ccatttaggc tgactggtat cgcccagggc 34560
ttcgcaatag gcacggttga cttcgtggca caggaaggca ataccacgat aatcatcgac 34620
ctgtgcgaaa tcacggaact cgtgattcat cagttgatca gctttgtcca gcatgtgacc 34680
catatctgct gactcggaca gcactttgcc agccgacatt aaaatcaggt gcattaacgg 34740
ctctggcagc ttatgaactt tcatcgtttc tctcttggtt caggttaatg ttcaaataaa 34800
aaaagcctcc cgaaggaggc tttagtaacc ttaacgcggt caacgaggca ggctgagaag 34860
tatagaggtt tgtgatgcga ttgattgtcg ccctcgtgtt cttctcatag atcatcacgc 34920
tctggagaga tggcaatgaa tttggcggaa agtctgggat tcgaacccag ggagctgtta 34980
cacccggcag ttttcaagac tgctgcctta aaccaactcg gccaactttc caatatggcg 35040
gaagatagag gaatcgaacc tctgcaacct ttcggttgta ctccttagca gggagctgca 35100
ttaccgctct gccaatcttc caaatatggt gggggatggt agattcgaac taccgtgtgg 35160
tataacagat ttacagtctg ccgtcttcga ccgcttgact aatcccccga atgaggatgg 35220
gcttctcacc caatcgaaca tttgatctat ccacgcacct tacccccgaa gggatgtctc 35280
gtcgcttcaa tgccagtgtc ttctggcagg tcttccggta gcgaatcgga atctttgaga 35340
gcgatggtta caagctgcca tcgtaccgga cactgttcag gggatgctcg cgttccggtt 35400
atgccccttg ctctcaaact ggttgcatca actgggcttg aaccagtgac ctcaccctta 35460
tcaggggtgc gctctaccaa ctgagctatg acgcaatttg ttgagtaacc ctggtttcga 35520
accaggatga acacctcgcg gctgtgttcg aagtcctata ttcgcctaag ctattgtcgg 35580
actctccgtc tacccattcc ggcagttact cataatttgg caggggttgc acgattcgaa 35640
cgtgcgacat acgggatcaa agcccggtgt tctaccaact gaactaaacc ccaattatat 35700
ggcaggacta acgggattcg aacccgtgac cactcccgtg acaggggagg attctaccgc 35760
tgaactatag tcctataaat ttggcgactc tggcaggact tgaacctgcg acacatagat 35820
taacagtcta ccgttctacc gactgaacta cagagtctcg atgaacaaaa gatacttcaa 35880
actaatgttg ctagtcaaca ttaagtttca tcagtatcaa cttgccaaag catttcccaa 35940
cggcgtttgc ccttggcaat cttttccttg agttcagcta tctcatcctc aaggtctgat 36000
aattcttctt cccacttatt cagatcacga gtttcatcac actcatagtt gcctgagtcg 36060
gtgaagcctg aacccacgtc atccttgtaa ccacaacggt gacaggtatg gtggcagaca 36120
aactggggat tgatgaacgg gctgtgcttg tactggtaaa agaatggggc agagcacaga 36180
tgattgttac tcacaattcc acagtcagga cacattagtc tgacatgagc gtcgaacagc 36240
atgatgccgg actggacaat ctcgtcatct tcttctggat caatgaacat ttgcttgggc 36300
ctctcgcctt ttaaatccgg gaatgatgaa attggtttaa agaagcccaa gaaaatgccc 36360
ccgttactct gggggctttt cttccttgcc accgaacatt gcgaacagag ccacaacgac 36420
gatgacacca acggcaatgt agggagccat tgcgatcact gctgtagaga tagccaggaa 36480
agcaatcaca atgaggatcc ctacaataag gatcctcatc ccagccatta gttagttggc 36540
tttttcagac caccgaacag agaagcacga ggtttggctt cggcctgcac ttcttcctgc 36600
acttcaactt gctgttcggc ctgggcatca gcttcgtcct taacttcagt ctgctgttcc 36660
tgctcgttca cttccggctg agtttccggc ttaacatcac cagcattggt cgcagcacca 36720
gctacaacag tgttgttggt ctgggtttct ggctttggtt cctgctttac aacaggtttc 36780
gcaacagccg gggttggttt agcagccgca gcagcctgac ctttcaccgg agtttttggt 36840
ggagcgatgt cgatgttcgc agagaaacct tccgggccac gaccagcttt cagatcgatg 36900
gtgatttcca taccatcttt gatggtgatc tgatcgttga tgtaggtttt cagagcggtt 36960
tcgatttctt gttggttcag agttacctgc atgactattt aacctcagcg aataaacgca 37020
ttaaattttg aaatactggg gtctgcaccc cagcatgaat agctgctata gcatcagcaa 37080
cgtgttcagc ttttacagct acttgcccac gatacatggg gaaattagca tcggggtaca 37140
gcttcactgc tgcatcgatc atcttctgct tggtggcatt tttgtcacca gtgaaaatct 37200
ttttggattc catagcagta acttcgatga ctgggatgcc cagtgatcgt attgccccta 37260
gcacaccaac cacaataccg taggctttca tgccattggc tgattgggag ccaacaggac 37320
actcaacgaa aacgaccttg ctacgtctgg caaccataat tgccgtggtt gcaaggtctt 37380
cagcacgctg aatatcgaca ctgttctgtc gtacctgctt gccttgtttc ttttctggtt 37440
ccacggtttg cagaaccaga tcgttgagat agccctgttc cagatccaac atgccttcgg 37500
caatgcccca gctatttaag ctggggtcaa acccggcaac ggggatctgc atctcttact 37560
tcttgttgaa gagagatggg cgtgcagcag cctgaccagc cgcagcttgc ggagcaccgc 37620
cagcaggttt accaccagca gcagaaccgc ctttagtggt tttgtcgatt gctggagcac 37680
cgacatactt ctccagccac ttgtcccaga actctggatc ctgagacttc tcagcttcca 37740
gcagggtcga gtgcgtttcg gtatggaaca cggcgttgat ctggttggtg tcacgagttt 37800
caccagtagg cacataggcg ttaccttcca gcttcgtttt gtcttccaga tacttcagga 37860
tgccgaagga gatttcctgg cccatagttt cgaccagggt cggcacagac ttaggcagct 37920
ctttctgtgc ttccttgtca tagatattga acactttgtc ttcaatatcc tgctcggaca 37980
gaggcttacc agtggcgatc acacagatgt tgttgaccgt ggtaaagcct ggcagaggct 38040
gcttcttgcc gtctttgacg tagaagtttt cgcctttctt gttggtaacg tacacggttt 38100
cacggtactc accaccagcg tgttcaaaca gaattacgac acccatcgca cctgaagcag 38160
cagtgatggc atacaatgcc ttcagcttgc cagaatagat gttgtggtcg agtgcggaaa 38220
agccaccacc cagacggtca gtttgttctt cgataccatc ggtggtcagt ttgctaaaca 38280
agctcataat attttctctt ttggttcatc attaagtttt ctctacagtc atcatcgtgt 38340
agagcttgtg gggtggctta cttgccgtaa tactgatcta aacggtcaaa cacttgctgc 38400
aaatcgttgt cgatatacag ttcgttacgt gaccagagat ccattgctga acgcatcttg 38460
ccaccagcag tctctttgga tacgcgagtg gtgaagacat acttcacacc atcttcacgt 38520
tccgcatcag tgatgtgcag gagatcattt tcatgacctt ccagcttctt gatgggaatc 38580
tgcatggttt tcaagatcgt ggtgaagtca gcttcaacac cgactttacc gacagcacct 38640
ttaatcggaa cacggctttc catcattgcg gattgctcgt tcagactttc gtcttcgtgt 38700
gccagaatcg catagctctt ggagcctgct ttaatggcat ggatgaggtt acgatagaag 38760
ttaccgtaat caccccacgc agactgacca gtcttagtcc cggcgtatgg tgcgacgaat 38820
tgacgctcgt acatctgcat caggaaggtg atggtatcca gtaccgcacc cgtcacatca 38880
gcgttttgct cgatctcttc gacatatccc agcacgtcag ttgcagttgc aatctcgacg 38940
ttagccatga aacgttcacg gaaaggaatg tctttcagat cggcgttgag gtaaatcatg 39000
ctctcctgag caaggttacg cagagaggta gatttccctg tgtttggctt gcccatgatc 39060
atgacgattt ttttgttctg gctcattaca attttctcca gtgtcagccc taaccaaaga 39120
aagggctgac cttcagttaa cgactttgat aacgttgggc cacagtacgc ataatggtac 39180
tgttgatctc ttcagcatcc agaccgttag acagtttgga gttaaaggcc agtacctgat 39240
tctgtactga cataagatcc ataccactat caaccagtgc caaggcatac ttgatcatct 39300
ggttattacg gttgcccata gcgatacgac cagcaaacca acgctccagg ttgtccatag 39360
actcaactgc ctggaactct ttacggtatt gctcgttctt cgaagtcttc ggaatgaaac 39420
gcagaacatc cagcacttca ccatccaggt tataatggaa ctcacctgca aagtgactgc 39480
cccatttcct gcttctctgg ttcgcttctt catccgtctt gaacggaatc cagctaacga 39540
tgtttgccat gaactctttg tattcatcgg catccagttc caacgtatag ttgatcggca 39600
ggattaaacg gaagtggtgt tcaccatcgg gatcatggct cttggttgta taaaccagga 39660
acttgtattc cttcatgaga tccataaccg tgtgcaggtt agcagtacca tcgacgtcaa 39720
tcgccagcag gttaaagcct ggaatcacgt tctcttcagc acggtgattc tttttgtacg 39780
catggttagc ccagtgcata ccttcggcct gaaccagaag atgaagctgg tcaaacggta 39840
ctttctcggc aacaaagttg tatgcccagt gatccgaata actgactgtc atctcattaa 39900
gatcagtctc tttcagcgtt tctgctttga agaactcaat cccatcgacg aatgacttct 39960
tgatgatgat gtgcttttta tagccccagg ctgttgccag actgatcatc tcattacgag 40020
cagccatgcc tgatttgtag aacggtaatg cttccagtag atcggcatga gtcacttcgg 40080
tatccaccgc agccatgtat ttcgccaact taacgtaggc tttctcacgg ttcaggatgg 40140
tctggaatgc agcaccagat tcttcaacca gcaggattgc agacatcaga tgcgacatct 40200
caatctcgtt gctttcgtca ataaaggcgt aagcaccagc cagtttcaga gctttgaagt 40260
aacggtgaga cagttcagct ttacgaattt cttcgtggtc gcccaacagt tcagcagcct 40320
tttcgcattc gatcttgtac gtcagcaact gaattgccac gtcatcttcg actacgattt 40380
tccagccata attgcctgga tcagcgagct tatggaagtg attgctccac ttgctcaggg 40440
cagcattgtt ggttggctga atcaggttct gatagatttc ttcaggcgtc agagtgttga 40500
acgctttacg gtcagtctgc ccccaggcaa acagacaacg gcgagcataa cctgtatcca 40560
ggaaatcata gaactggtct tcggtctgag caccatcaag cagcttactc ggcgtaccga 40620
acagcagcat gttagttggt gtcttaccgt caacctcttc accacgctgg ctttcgccag 40680
tgtttttggt cagcttctgc ttaaccatac cctgatcata aagttcaagg aaaagcgtca 40740
gaacttcgac gttattgatt aagttagagc cgatctcatc gatctgaaga ttgatggaac 40800
cgcaggacgc cagcagtaat ttgtggcgta attgtttaac ggcaggtgaa gtaccggagt 40860
caaaggtgaa cgggtaagca ccagcacgct taaactcacc ctcaactttg tcatactctt 40920
cctgtggatc agacgcattg cgtaaggcac ggtcattggc aatatcccag agagatttgt 40980
cagcgatcac tggcagagtt tcttccacga aacgcttctt aaagcctttc atgaactcag 41040
tttcaacgat gttgactgag tgacctttac cgaatcctga cgttgccagg gccagtgcat 41100
aaatgttaac cgggatgtct ccacggtctt tcgtcatgat ggttacacgt tgggacgctg 41160
ccatcttgcc gagaaaatac gcacactcca cgcggaagaa accacggtca gtgttctgcg 41220
ttttgttgca gagaacatca acgagttcct ccagcactgg gtggtgtgct acaccttcca 41280
gattgatcat aaatatttca gcctttgttt gcacaccgga gcagcttcgc aatattcgca 41340
acgctttggt gtgcctggga ttgtgataac gataccttta ccacccttct ctacctgcca 41400
ccattggtta gcttcaccag gatcgttgaa gttcttggtg gatttaccag tggttttgga 41460
cgggtcagaa taatacttgt agacgggttc agacatccac aactcttctg gggtacactc 41520
agggatctct tcgtccgggg agtttttata cttctcgaac atggtgattt tgtttctcac 41580
ccagctatcc gtgtcccgaa tatctttcag gcgaatgtct ttgaactcga cacgtttctg 41640
aggataagca gggttggtac gggcttgcag cttctgccag tcagtgaaca ggaagttaat 41700
acggatgaaa tcctccgtta tcttctctgg ttccaaccaa cggtagatac tgccctgaag 41760
ctgatagtca tcgtctttgc caccaaacaa ccaggcataa gctgtggtcg atttgttgtc 41820
gtgtacgata ccttcagcca ccatatcgaa cttaccaccg atggtgtatt ccacacccat 41880
gatgaccact ttcttgaagc aacgctgttc cagataaacc ggaatagcat caggcttcgc 41940
agcaagctgt tctttggtag ggttgaccag aatacgttca atgacgtgtt ccgggtagcc 42000
cagttgtcgc aggccgttat tacgtgcctt atcattcgtc cacgctttct caatggaatc 42060
gtgaagcgag tgaccatagg ctctggagat gtaatcctcc aggtctgaca cctgttgatc 42120
tggtggcaca cgggcagcaa gaatcagggc acgcaaaggc ttcatcaggc gagtcgcact 42180
gatgtaattt gccatgcttt gataatcgta ctcgtcatgc aataaccaga cacccagggc 42240
cagtgggatg tttccagtat tggtgatttt caagggagat ctcctcagtt aacaacagtt 42300
agctactgcc aatcaaagac tgatagtagc taacggggtt aactgcgttg tgccttgcga 42360
agaatacgcc cggcatagtg aaccactttc tgagcagagc gtaatggagt gttacctgct 42420
ttgcccagac cgttggtacg ttggtttgct gtacgccaga tctctttaaa gatattggcc 42480
tcgtcaaacg tcatacccag tcggtcgata atatcttcac actcagcagt gtaagggggt 42540
tgatcttcac gctgtggatg cgtgatgtca gccaggtaat aatttacccg gcccccagac 42600
gactcactgc tcgacgaacg ggtctgactg gtcatctttc ttaccacgca gttgagtcac 42660
gttgccattg ctgatgttcg cagacagttt ctgtgcttcg ttcatcgcag gtgggatata 42720
cgcaaactct tcatcggtca tcagaccgag gttggacaga ccgatcacta caacatcctg 42780
aacacggatg tactgtgcca tttcgccagc acgcttcatg tggtgcattt gcagagactg 42840
ttgagcacgg cccaaggcat tggcaccaac gttaccgtca gcagtggtaa ttactgcatt 42900
cagttcgatg gcatgaatgt ccaggttttc gtcctcttcg gtctggcctt ctttcagcag 42960
ggcgaagatg atcttaccga caacgaggtg atggtactta cgggatggtt gattcggttt 43020
gttcacagga actctccaga tgggttaaag atatgttggg gtagctatca tagtcccaac 43080
caaataaaaa ggccaccctg taggtggcct cggaaccaaa gaaggaactt acgagctgat 43140
agccgcaatt ggcgtcagtg tgtaactact ggtcttcagg atgttcagcc agtatgagga 43200
gttcactacc atagctttaa gctgaggtgg tgtggttccc acatagttga actgaatcac 43260
accttccaga acagcgatac cttcctgagt tgccccggta taaaccagca ggccagttgc 43320
agcctgatca gatgtggtac gtttcagaac accagtgctg tcagcagaca cggcagacat 43380
acggaatacc tgagcaccca tattgtcaaa cgtgatgttg aatgagccac caacggcacc 43440
ctgagtcagg atcacagctt tgaacatgta cagcgtgttg ttcactggca gcacagtacc 43500
tgtgaagccc agagatacag cagcagttga actgatgcta tttgcatcgg caggcatgta 43560
tgcagccgga atgcttgtac caccgccacc accacccgaa gacgggccaa ccagtgtcca 43620
tgttgtctgc caggttccag cagtctggaa acgcacatag catttgccag tgtcgttttc 43680
gattgcgaac tgtgtggcat aaccatcgcc ggacgggata cagaacccac gaccgtaagt 43740
tccggtcgct ggaatgttcg ccgtaccacc agaagcagca ccggaatagt tgaaaaatgc 43800
tccacgaaca accaagttca ggtcagttgc ctgagtggtg taagtggcag tcagaccata 43860
ctgttccatg tactcacgca catgagcagg tgtcatcagc accaagttac tggttgcatc 43920
tttcgcttgc tgggtagtgg caattggcat aatcacacca atagcagccc agctcgtagt 43980
ggcacgatac caaaccacaa aggtcgaggt attctggtag tagttaccag cagcacccgt 44040
cgagctggtt ggatcggaag taccgttcaa ccaagtggtg ccaccggagc ctgatccacc 44100
agaaccatca acaccttgat acgccacact gtaagcagtg ttggttgacg catcggtcag 44160
tgtcagaaca gtacgagtcc acaggaatga accctgagcc acagtcggaa tggtacttga 44220
ccaagttccg gttggtgcag tcgttccatt ggttcccacc tgataagtgg taacagcaga 44280
actgacaccc acaccagcag aaccatccgt accaaagtag gcaacgctgt acgctgtcgt 44340
cgggttaagg gcgtccgtat aggcagttat ggtacgagtc cagatgaact gtcctttggt 44400
cacagcaggt acagttgaag accaagtacc tgttggggta gtggtgcctg atgctgaagc 44460
ctgatacgtc accgttgcag agctgacacc tcgaccgtta ttcccattgg ttccatccac 44520
accctgatag gctgcactgt aaccatacgc gatagtgtca tcggtcaggg tataagtgct 44580
gcgagtccaa aggaaggatc ctttagccac ggcagggata gtcgtcgccc aagtgcccgt 44640
aggaacggaa gtaccggacg tcgatgcctg ataagtcatg accagagagg ccaggccaac 44700
accgttgttc ccggcaggag cctggaactc aatccagtgg gtcagatcat ctttcggctg 44760
aacagtcgaa acataatcct cagtaccgga cagaatccac atggagttgt taccgtctgc 44820
gttatccgca aacacgtaat caccaggtga ataggttgtg ccagtggccc aagcctgacg 44880
gttattcaag ccagtaccgt ctttaccatc agcaccatgc agtgactcca cccattgagc 44940
ttcagtcagc ttagggttgt cgctggtcgt gtccagatag gattggtaac ttgatttccc 45000
tggatcccct ttaatagagt ccccaggatt acctttaagg gaagccaccc aagcagactc 45060
agttttcact gggttatcgc tggtagtctt cacataagac atataggcag aatcaccagg 45120
ctcacctggt ttacccacca gagatttaat ccagtcagct tcgctgagta ccggattatc 45180
tgtagtggtt tctgtatatg actcgtatga cgatttacca ggatcgccgt tgttgcctgg 45240
tggcccctgg tagatagtac ctaccaggtt tagagtcaat gggctgtcgc tcatcgctgt 45300
gttactcctc ttacaatttg aactggcatg atgcttgaac gcatcgactg cccatcgact 45360
gactcaaaca gaacatcaaa ttctgcgagt ccaacgggcc aattgtcagt aagatcgtga 45420
gataacacaa gctgcttggt cgtactttcg ttcgtccagt agcattgcag ttgagcaatc 45480
atcccagaag gaagattgtt atttgcttta cggatctgtg cagtggcttt ccacttgcga 45540
aagaaaccgt taccaatcgt atcggggatg tcaaacacgt aattaaacgt ggcccccttg 45600
ctgtgctgta ggatgctcat ctaatcgcct taactaatgg tacatgccag agaagatgac 45660
agattaccaa ttgcagcagt aatagtcgct gatcctgttt tagtaacaga agtcacctga 45720
cctgttgcag ataccggagt aactggaaca gcagcagtat tggttgatgt ccatgatgca 45780
acagcacgag ctgtgctcag accgtttggc gtaaacgcac tgtcatcact gaagcgagta 45840
tagaaagcag accaataacg agtaccacca gcagcactgt gggtatacgt tgtgttggtg 45900
actttggtag tacccagaga cgaaccatta ccagcactcg catcattctg aatacgcaga 45960
taaacagaca ccacatccac agatactgag tacactgggg ccgagtttcc atttaccact 46020
ttcagacgat aagtagctgt agcattggtg gcattagcca tgctgagaac agcagcagtt 46080
tgacctgcaa catctgacca gttagtgcca tcagttgatc gttgccactg ataacctgtt 46140
gccggggatg cagcagcacc tgtaatagtc agcagaccat tctcttgata cagagactgg 46200
gtttgcggtt gagctgagaa tactggcact gggtcagcag cccctccacg agagaaggaa 46260
ctgcgtgaac taaacgaccg agtattccct aaagggaatc ggatcatacg gcgaatgcct 46320
cccctttcac agtcacagca gtgttggcta catcaacacg gcgaacacca agctggttgg 46380
tgttagtgat gcctgtgatt aaacggcttg aaccagcagg gatagtaata gctacgccag 46440
caccgttacg gcgatattcg atagcaacac cagtgtcgtt gaccagatcg aatgcgacac 46500
acgcattaga gccgaacaca gtccacgttg caccagtggt gtttgtcgcc acactcacac 46560
cagtaacact ggagtaagtt ggcatcttaa tctgggcctg gagtgcagca atggctgtca 46620
gtaccggagt taaatccgta cctgatccac cgcctccacc cggcagggtt ggtaatcctg 46680
ttacaggatc gcagataaca actgccacag caggcagttt actcattgca tctccattgc 46740
gaatatcaat gccaggagat aggatagtaa ctggtgtcat tagaagtgct cccaagaggt 46800
gaggatggta ttaccatata gataatacca tccagcctat taagcagcca gaagagacag 46860
aatctcttct ttcttggctc catttggtat ggttgtttcc tcacaccaag tcgggaagaa 46920
cactgaaagt tccccaccta atcccacttc tggatgtgca atgtctgggt gattttgcca 46980
gttaacggct tcaaccagat gttcattggt aaattccaga gcatccaaat cctcacggat 47040
cagataatac tgggcatcat gaatgtgggc acacggtcga atatcttccc ggaaccggga 47100
aactcgtacc ttgcccatga actcagatgc agcacgggag ttaagtaagc accagctttg 47160
acctaaagca ttaccagcag tacgcccttc ggcatctgct tctcgtggcg tcttgcgggt 47220
tttacgaaca acttgatgca gcaatggtgt acgtacacgc aacccaaagg cgacagtgac 47280
ataaccatct ttcgctgctt gatccagttt tccgttaacc cactcaacgc tcaccttata 47340
gagatcgagg taacgctgtt caaccgtcat ggctttctct tgtgagaaac cacagttggt 47400
catcagagta cggtgagtac cctgataggt cagagcaaag gtcggtgcct tagagtcctg 47460
acggaatggt ttatacagct tctcaatcga gttgatcgag tccactgagt tagggtcaat 47520
atctggcata gcttcgccaa agtaggcata tgctcgcaga cagtgaccgt cataaccgtc 47580
cgtatagact ttcagcttct ctggatcctt ggttgtaagg gctgagattc tgtcctctaa 47640
agaggcaaaa tccagacctg caaagatcca gcccggtggg gcttcgaagc aagatttaat 47700
cagcttcgca taacgagagt ttgccgggat gttctggaga ttcggtttgc tggacgacaa 47760
gcgaccagac accgtaccac ccaggttgaa gttaccgaac atgtagtgcc agccatcgtt 47820
acctctggca gcacgtttca tggcaggcac gaatgtagac aggatgatta tcacatcctt 47880
gaagtccatt aacgcagcca gaaattcgag gatctctgga ttgtcagtgt ggttcttcaa 47940
tgccttcagc gtgtcgccat cagtgcttgg ctggcctgag tcagtcttgc tgagtacagg 48000
caggcccaga tccttaaaca ggaactgttg caactgctga tcgctattcg gattgaactc 48060
gatggccttt tgaatggctt tgacatcaca ggtcattact tcctgtattg tcatacgctt 48120
cgttttccac ttagcgttca tcttgttcgt tacacgttcc accagttcat acttaaattt 48180
ctgaaccaga ggaagggctt ccatcctggc tacggagtca tctttgtcct tcgttaagat 48240
tttctccact tcaagcacac gagtacggtt aatcggcatt ccggttaact gcatctggat 48300
aatatccaga atggctggtt tgaatatccg cagataaata tcttcctgct gatcagccac 48360
catcgtttta tagtgcttct catgaacgta ccatgttgaa agaccgtcca cgaggttgta 48420
tcgcaatagc tcattgagtg gaatcttaca gatgtcctta atatcttctt tggcatagtc 48480
accagcatat tcctgtgcct gatctttcag gctcagttta ttaccagcac atgaattggt 48540
tgccagatag ctaattagct tcgtgtcatc ccaattacgt aacataatgt ccataccatt 48600
cagcagacct tttgtgtcca gaatatcagt cataaataac tgataaatca ggacatacac 48660
gtcataggca atattgtgat atacgccttt acgcaggtat gcaataaaga actctttgag 48720
catcttacgt actgcatggt ttttcacttg ctcaccgaat ggggctttaa cagcaccagg 48780
gataggcttg taatcaaccg ggaatgcaat accttcgtgt ttactccacg caaaggtaat 48840
ggttccaata ccagctttgt gatgtttcag atcaaaggct tcaatatcaa tagccaagtc 48900
tcgatccatc tccagaagtt tatcaagcca ctgtttaatt tcacgttctg taagcggata 48960
ctcctcgaac ttaataatac tttgcccagg ttcctcatat tcaccactgg catgatcaat 49020
caaggccata atagcctgac tgattttact ttttactttc gccgggtcgt agaatatctg 49080
acggtagctt ggggcatata aagcctttat accgtattca gtatccatga cataaccgag 49140
actggcctca gctttagcag ctttggtcag tgccttgaaa tactccgcat cggtacagat 49200
cacatactgt gtctctgcct ctttgaagat aggcactaac tcttcgctga tgtactgacg 49260
catctcagcc ataggcgttt tctttttacc ttctgcctgg tgcagatcga tagccagaaa 49320
atcctcttcg ttcagtccga acggtcgaat ataggcatca gccatatttt cccgatggag 49380
cgaaccagag aggataacca ccggatactt ttcttttggt tcagcaaata tgcagtgacg 49440
catgtaaccc cctaaaagaa catcctgctc acggaataca cttccatgag tgggagtgct 49500
ttgtggtact gacggagtaa cctttcatcg tttccgatca cttcttccac cgagcgaaca 49560
cgctctatgg cttgaagttc aggaaccaga ttgacaatac aatcaggcaa cgcatcacgt 49620
tgcttctgga gtgtgttgca caggtacagc agacgagtaa ccatctgccg gatcatggca 49680
aactcctgat cgaacagtcg tctgtctttc aggtgaacat ccatctgagg gcacaatgac 49740
caggctaaag ccgggagtcg tgagtgcatg tttgcattac tgcgatagta caaatcgccc 49800
tgaaacatga agccttgatc attagtctga acaatctcct gattctgggc taccagcttg 49860
tcgatcacat tctgaaggcg acgagtctcc ggctcgcaga gacttgccac tgccctcata 49920
atgacagttt tgtccagcat gatgcctcct aatgaatgag gccaccgtat ttctcgacta 49980
aatcgccgta gaagacgaca cgatgacggg cacggctgat acctacataa agcaggcgag 50040
cagccaggtc tgggttacgg cagctactta gatcatccag atcaatcagg ctgatgtcgt 50100
aactggaacc ctgagacttg tgtaccgtac atgaatcacg aggacgtaga tcggggtagg 50160
tatttttcag gtggaaataa ggagtccact ctttgcactt gccgtaatac ttcaccaacg 50220
cagtgtggtg atcacggtca actggcagag gcacacccac cataacctca cccaggctgg 50280
tttccagatt ggcacgaatg atttcgagat agactttctc tcttggttca atcagtacca 50340
tttctgtggt gtcagcaagc tcaacaatag tcacttcctg ttccacagaa atcatgcctt 50400
tacctacctg aacagcagag ttgttcacga ggatttcacc tactgtgtac ttagcaggca 50460
ggccacgcag ttcacggata tagtcgttgt aattcacaac ggttttattc gtataggcca 50520
gcagacggga tgacgattct gtctgaataa acagatcatc caccagtgct tgcatctgct 50580
caccgttaag gtgatcgata atgccaggca caatctgaat tggtttgaac tcacctgtct 50640
caactgtttg gcgtaactga agattcagtg ccagcagttc aggcttgtca gttcgcatcg 50700
gctcagtcag ttcaaagaac ggcaggttgg aacggtaaat aggagatatg acctccatca 50760
ccggagccaa ctgacagtga tccccaacgt agataatctt gcaggaatga gtaccttcca 50820
gaatcatctt tcgcagtggg gtatcaatca tggaacattc atctatgaag atgattttat 50880
tccgatgaac tgtccagttc ttcgttttgg tgagcttact acgcccactc tcataatcgt 50940
cctgaacttt caggccaagg aaagagtgga tagtcgaagc agggcgacca gtgttgagtg 51000
acaacacttc agcagccttg ttcgttgtag cagtcatcac gacctcgttg tactcaggct 51060
tgatgcccat gagcttacaa gtgtcgtaat actgaggcat gatctcatcg atcaagtgcc 51120
ccatcaggaa ggtcttaccg accccaccag ggccactgat atttagctct ttatcagttc 51180
ccatgaggaa tgcaaagaag ccatcggcag cggcctgttg tccctggttc agaggtaatc 51240
gtttcacttt cgcaggttct gcgaatagct catcgaaaaa atcatcagac atgactttct 51300
ccaaaaggaa aggccacctt acgatggcct gttattagaa gcgaggtgca gcagcgaatg 51360
gtgccaggtc agcacggaag tattcctgac ccttcacaat tttcttgttc tggtcgaaca 51420
ctggaacacc gtcctggaac ttggagaagt tggaacggtt tacttcctgc atcccagaca 51480
ccatgagata gcccagcatg tagcctgtgc cagttgctgt gacaatctgg tcacacagag 51540
catccagcat cagcacgtta tcagtgactt caaacagcag atgatcgcca ttggctttca 51600
gtgctttagc cagtgacttc agggctgctt ctgcttcctg gatcaggcga taggtttctg 51660
gcgtggtgcc gaccatttgt tccagcattt ctgccacttc ttcaaagtga acacccgttt 51720
gagcattcac attctgaatg gttggctccg gtacagcagc attaaaccag cgtaccgtgt 51780
cgcgtaatgt atccatcaat tcctcacttg cggttaatgt atgcctccac cagaaggttt 51840
ttcacaaacg acttaatcgt tatgcttggg ccgagttgat cggctaacca ttcctgttga 51900
ggctcagaga gcgtaacaaa aatatcttcc atgaaagttc ttcgggtatc agcaggatcg 51960
ataccaagag ctttcaggcg aagagtgatt gtagtcggat gaacaccaag agcatgagca 52020
atggtggaca gcgataagcc aacactattc atacgaataa tgtcatcatc agacgctttg 52080
cgatttgcac ggaatacttt ggacattttg tgacctctca taaaaaatac ctctagccta 52140
ttatggctag aggtatcctg gaagtcagca attacttgct gtgtttttcg atttccgcct 52200
gttctgcttc ggtaacaccg agtgcagccc agcctttctt cgcctgcttc ttcgccaaca 52260
ggatctgctc aacgttctga gcaataccgt tgtcgatagc agcacgaatg atggtacgag 52320
gagaagaacc agcaggacga gacgcaacag caggtttatt tgcttttggt gccttagcag 52380
atttggcctt agctttcgct ttggctttct tcggcttggc aacagttgcc ttcggtgcct 52440
gtttgtcttc agcagtctgg atgtacgtat ggatctggct cgcctgttca tcagtcaggc 52500
cgaggccatg ccatgattta ccagtgcgag ttttcagagc catcagctcg actgctacct 52560
tgtgagcgtc attaggcgtc aatttagaca gcgagacgaa gtgattacgc acaaactctt 52620
tctgtgacat ttcttcttga tccacaggtt taacatcggt tgcaactact ggtgcagctt 52680
ttggctgttc cagatcttcc ggcagaatat ccgcaccgac tgggatcact ttgttagtga 52740
tctcagtttc gtcgaacacc atgcgtgggt tggtgaactc tgtctgctgt tccaggatcg 52800
tcaggttact accctgctga ccaccgattt caacagtctg cgtgataccg atatggttgc 52860
cacgcatgac gttgttcaga actttggcac cgagtggttt atcactcagg ttgccaccgc 52920
tcgtgattaa agcagccagg tctttcggca actcagccac gatgtgatag cccgcaacac 52980
gcattttgtt atggctgtac tgaggcacag caaacacgtc ttccgggttg attttcacca 53040
tgaccatcac actaccactg aagctacgca ggtagctctt agcagcaatg tgcagaccgt 53100
tggaacagtc ttgacggcgg tttggatcga ccagaccgtg acgcatgaag acgaaagaac 53160
ccactttctg aagaaccttt ttggtatgac agtccacgaa tgcaccgttt ttaccatcca 53220
ggcgtttgaa gccgatgatg cagccatcat cagccagtgg cagatcggcc tggtgaagaa 53280
acttcatcag gtcttctacc gagtgaccac gtttatccac gacagccgac agacgttcga 53340
agaacgcctt aaagcctacg tagtccttca gctcactcgc agctttcagg tgtggtgcca 53400
gtttctgagc atcgggaatc actgcacccg tctgtgtgtt gacggcgaca atggtttcct 53460
ctttctcatc cagtggctta tggaatgctt cttgctcagt gcttacagca ccgttgccga 53520
ccagcagatc cattttagcc tgagcagccg ataccttttc cgcattggtc tgcggcagag 53580
gttccgcctt cttttctggt tccagctctg gtgcaggcac ggtgtcagac tcatccttga 53640
ggggatcggc ttcgttcatg gttaatacct tgaacttcag accatccacc tcttccagga 53700
gagaacgacg aaccgtagct tgcagctcag tcagatcatc agacagcaaa tacggcagag 53760
gttgctctga catatcctta gcttctttca gaccggaatc agtacaggca cgcagagcct 53820
tgatcagttg gacacggttc acacccagag ggtatcccgt gatccagact ttccacttgg 53880
tgcccacggc agtagcaatg gtgtcttcca ccttcactgc tgcaaacggt gacacattag 53940
aaccagggac gatacccagg ctcagtggtg tgatgtgctc tgcttcggga gcaacagccg 54000
ttggcgattc ggtgttgacc agcttttcca cgaacttttt ggctacgcgg aagaacttga 54060
ccagtccacc agtacctttc tctgcttctg catactcagt acgctgggcg aagatttcgg 54120
taatatcgac ttccactggc tcattacgag acagtgggcc tttggctgtt gccacgatgt 54180
taggcaggcg aggatcgcct tgcttaatca tcacggtaga accatcctct ttatagaggg 54240
tggcatactg cgtatcaatg gacagtgcca cgatagtgat aaacactttg ttcatgagat 54300
cagtttcctg ttttaagcgc gctaagaacg agggatttaa gagcagcttt tcgctccggc 54360
atagccttca tgtatttgat aatacgttca ggactgccaa tctgacgcag caagtcgtca 54420
gtcttcattg ccttcacctt acggatgaat ggcaactgtt ccagcttgta cttcttcacc 54480
tcatcagtga gcttgtcaca gagttcggca gagatttcgc cacgagcatg tgctgctttc 54540
gggctgtacg agtccagaag ttcaaagtgt ttctcaaact tcggattgtg gaataatttt 54600
ccataaccgg gcagagtaac accaagcaaa cgcaataact tcagatccac agagtgaatg 54660
tagtggtcat cagaaactgc acgctgacgc tgcttagtca tgtatttctt gtactcaggg 54720
gagagcacaa catccataaa gcgttgacgg aaatactcat caacatgaac agcaccacgt 54780
ttcacagcca tgttacgttc gataccattg cgaacaacga caccatgcag acgttcatca 54840
tctgacagcc acgggtaaaa ggtgaaatca cccagttgcc cattggactt ggcctcattg 54900
ttctccataa agaacagggg ggtttcagta atgaactcca catcgtcttt cagcaggtca 54960
gatacctctg agccacgtac ctgcttgtcc cctttgtcgt catacagact cttcagggat 55020
accagcatgt tcacggactc tttcttttct ggttccttcc cttcagcttt ggctttcgcc 55080
ttagctttac gttccagatc cagagagaca gcaactgagt cccacttgtt gactttggtc 55140
aggtcaatga cttcgtaacc agcatcagtc aggtatgcga taactgcatc cacatctgag 55200
gctttattga cacgaacagc ccattcccgc atatcgctaa caggcgtctg agggcaattg 55260
gctactgact taggcagatc tttgatacgt gtggtcacaa agattcgctt gttttcaata 55320
ccgtttcgca gatccttgat gctctcatac tcatcgtacc aacgggtctt aatgaccatg 55380
ttgttccagt gggtattttt aaccatcagc agatcacggc ctttgatcag accgttactg 55440
tcacagacca gtttagcttt tggcttaacg atgtatttct gtgcagcagc ttcgacaaca 55500
cggctctcat aacgcaggct tttaccacgc ttgctgttaa ggatcagcca gtgctgttgg 55560
atcaggaatc gggccacttc acgggagaag tttgctttag catagagctt gaagccgacc 55620
ttcagaatgt cccataaagc agggtaatat ttggtacgga catctttgcc cagcttagaa 55680
cgcacatagc gttgtactac cgggttttgg atgttctgcc agaagtcaat tttcttaccg 55740
aacatacctt cgtagttgta acgacgagtg taatttttca gttgttccgt tgtctccggc 55800
aattttgcca gaatctcttt ctcaatctga tccaccagat cgacacagat gtcggtgata 55860
ccgtcctctg tcatcttctg gctcgacaat gcctcacggc ttggggtcag agcgagagtg 55920
cttggtgcag cctgaactac gatgcgggta tagcccacag tctccatgaa ggtttcaatt 55980
accttcagtg caggttctgt tgccggggtg cgtaacgcag ggtaaataac tgcaccatag 56040
cgaatgaaga ctttgtggtt ccccatatag gagaagtgcc agcgagcaga gtccaggtta 56100
taggaaccgg gttcactcga catacccagt tgacgcaagg gtacgaagtg attgagattt 56160
tgcggtacgc agcagaactg cacacgcata tcaccatgca gggagattgc ctggatatat 56220
tcgacaatct catccagatc atgttcttcc agacgaatgg tgacagtcag gccagtgcga 56280
tcagttggta ctgtcatcac tggggtaatg cctggcttac catcgttctc gatgcaggta 56340
cgggccatgt tatagaccgt cttcttgccg tcgaactctg aggccacacg gaaagattcc 56400
acgtaggccc acggtgattt actgcccaga ccaaagccac cagtggttgc tttgtcttcg 56460
cgtttggtag aaccaccata ggtgccgtaa atctgatcga tcaagtcgtc agaaataccc 56520
ttaccagagt ccttgatgat caggtcatgg ttggcatcaa tgctcaccat aactggctga 56580
tcagtagttc ctgcctcgat gtgggcatcc caggcgttac acagaacttc gcggataaac 56640
gcaagtttct ggttagagta gaggttagag gacagcatca tgaagaatga cgcatcttca 56700
accatagaca ctttacgggt tgcctgagca ccaatagttg ctgacgaggc ggtttgagta 56760
ttatctgcga cttgcataat taatctctcg gatgtttgga gttaagtacg gtgtttgtta 56820
catgcgttga agatagcttc acgcatgtta cgttgagaag gactctcgtc ttgtggacga 56880
tgtagtgggt tttgaaccag agctttgagg gcatctaatt cgtttggtga cagatccact 56940
acaagacgga atactgttac ctgagttact tcagcattag ccattttcag gctccttcgg 57000
cagtttgcca gccatagcct gcaatacgaa tacagccata tcagaggcca tgtcatcggt 57060
aacatcatca acacaccagc ctaaatggtc actttcccat tcatccagta tgcgttgaac 57120
ttcagctaaa cctgcctgaa ccatttcagg ggtaggttct agccacaatt tttgttgtgc 57180
ctgcatacgc agagcttgag cagcaatagt gtcagccaag ccttctgcac cagtacgttc 57240
ggacatagtt tttcctttgg ttcagtggtt gagtgtttac agcgaggctg gtagccctca 57300
tatgaccaac cgggccacag tggatcatta aggtttggcc ctaccaacct ctctgtaaag 57360
actcaataaa aaagcccgga cgaatccggg caaacgttac aaatggggat ggctcacttg 57420
ttgggtgaac caagaaaaga actaacctgg gtaggtttcc cctggtaacg ttttacggaa 57480
ctgaatccag ccacggaagt tgccatgcaa cgactcgtta tcccacagtt caccaccgta 57540
atcagtagag tacgatttgg tgtctggggt ggcttgatgt tcagcaggag atgcgtgcag 57600
cggggcagaa cccagcagac ggttgtacag tttcagatct tcatccagct tagtctcacg 57660
accagagtgg gttaagtaac tgacacgagc acaacgggcc acagacactt tcagtgccat 57720
gtccatcatc tctttcactg acggctcatc acgagtgata cggttgtatt tcagctcatt 57780
acggatggct accatatcgg cagcagtcac gtaaggaaca tgccaatcac ctgaggccag 57840
ttcagtttgc ttggactgag acatcgccac tttcatcttt tgtgcgagtt cacggatttc 57900
cggttgggca tcagcatgat cacgcaggtg gaagaagttg gcgaagtcag ttgcagtgac 57960
cagcacatta atgtgcgacc acggctcaag cagacggttc acgatctgtt tgtgataacc 58020
agcgttgtcg aaaccttcag caactttgat tacacgatca cgagcgataa gccaggcttg 58080
ctccttcgac acaccgacta atgactggtt cagatcggtg agtaccggga gttgcactgg 58140
ctcatcaatt tgctcatgag cctgcatacc ggggatgttt tttccccagt gcattgggat 58200
cgccggatca ttaatgatgt cagcaatgat tttctttacc gggatagcac gactgcttga 58260
cgcattacgg ctgaacacac ggtgagtcat tacttcggca tggatgaaac ggggatagcg 58320
cagttgcagt gtcgtgatac ggacaccgtt ggcgatacta tctgctatca cctgagcaga 58380
aatggtcatt atgctttctc cagcagttca cggaacagct tatagctctt acgtgccttg 58440
tgagcgtaga taaaggacat taccagcgat accccaccca ccagcagagt caggccactg 58500
ttgaacagtg tggcccactc agaaccgtta atacttaacg atccgaaggt ggtaaagggt 58560
acggcagcaa caataacgaa cagcagcaac gagaagatct cacggttacg ccatgagaca 58620
taatcgtcaa acgcagcaaa caggttttgc attattcacc atctgggaga gtgacgtagg 58680
acacgctcgc catgacaata agttcacggc gaatgtagat tgtacgcatt gaatcgtgca 58740
accattcttt gaccgttacc aggcttggcg ttacagccag gatcgtgcca gacacttcta 58800
caccagtgat tgtttcaatg gtgaactttg gtgcctggtt tacggcaacg actttctttt 58860
catgctctga cagcacagct tcgatgcagt catcaaaaat ttcacgcttc attagaacct 58920
ctttttaccg agatagaatg gcaaggcatg tgccttacct ttagttgttt tgctgaccag 58980
caattcacgc ttaccaacct gcaccgtttc ctctttttct ggttcagtca acatcattga 59040
catatcacca cgaaggtcat cagcgatgat cagacgagcc tgtttgccac taatggctac 59100
agccagggca cggcgttcca gagcagagaa gtccagtccc atcatctcag tgaggaactt 59160
aactttctct gggggcatgt ccacgttcac tgccttgaag aactcttcag gagtgatagc 59220
attgacagtt acctgaccgt cttcaagctg acggcagagt attccacgac catttgcgac 59280
agcagactca atagcctgtt tccactgttc ttttgacgac atagcagcct caacaattga 59340
gagttgcgat gatctcttta accgacaact gaccgcctac ggcacgggca gcatgaatgt 59400
ggtggacgtt aaagtctgag tacagatcca acgacttgcg acagaaactg ttcgacacga 59460
cgataggaat accgtactgg cctaagtcca ggagagcatc acgcagtttg atttgatctg 59520
cttctccaaa gccttccttc gtgtaatcac tgaagttggc agtgggagag atcgggatat 59580
atggtggatc gatgtaaacg acatcgccct cacgaacttg cttcagagtg tccagccaat 59640
caccacaaaa gagttttact ccttgcagct tttcactggc attaataatt tctacacccg 59700
gcacagctac gtttttacgt ttgccagatg gaacattgaa agcaccactt tggttgtaac 59760
ggcacaggcc attaaaccca aacttgttca ggtagaggaa catggcaccc atctcaagag 59820
atgatgcagt tcgcttattg aacaggtcac ggacactgta ataataagga tcaccgtgag 59880
tgttaaacag gtactcagca gcttcgatca ggtcttcagg ccgggatttc accaggctaa 59940
agaagttgat caagtctggg ttgctgtcac cagccaaata aaaattgtaa tcagtattca 60000
gcatgacagt acaggaacca gcaaagggtt ctaccagacg tttacctttc ggcaagtgtg 60060
gtgagagttg gggcatgatt gacgccttac tacccaccca tttcaaggga ctgcgcataa 60120
aaacctcttt gcttgttcaa atgaaaaagc ccctacaaga ggggcttttc ctggtttacg 60180
gacgcttatt ctgcgtcagt atcgccagca acagccagac cttttttcac gtaaccgcga 60240
acagagcgat agctctcttt cacgttcagc gaaccgccga agccgaacac gatggcagaa 60300
cctttgtcgc cgttgtcaac tacagccaca acgtgtgctg cattgatgga atgcttggtg 60360
ccgttttctt cagaaacttc aaacagttgt tttgacattt ttggatctca cttttggaag 60420
attgcaggta caggctcatt agcctgatcc tgatatttgc ctgagtaaca ggccgattct 60480
gccagctcgt gaaacacgac ctgagcaata cctgcaccag cagggattat cagtgtttct 60540
tcaccgtgat acaccagctc taaagtcagg aagcctgacc agcccggttc aatcactgtg 60600
ttgaaaactg acaagccttg tctggcccag gtggatttgt catgcacaat accaacgagg 60660
ttggttggca tctgaaactc ttcaacggta gaggcaagcg taaacttgcc cggcttagtg 60720
ctggaagcaa cggagatacc gttttccatc acagagactt ctaccatgcg agtatcgaac 60780
ttacgaccga agatgatttg ctgggcacaa cgaatgtcgt aaccagcttc acccaaacca 60840
tgagaaacgc cgaaagcctt tttcttccct ggttccatgc ctttgatagg ctcgattttc 60900
cagagttctt cgccattaat gaccatgtta ttcctttatg tgaatgagtt tgccaaaagg 60960
aacacttttg ccagccttgt tgcatatcca caatagaggc aggtcatacg taagcggttc 61020
cataggatct acttccagat cagtaaagat catggcagca gtcggtctgt tctgttctat 61080
ccagttacgg acacaaacaa gggatgtacc accccgacca caaatttcca cttcggtaaa 61140
atcgtcgtct tcctcgaact catagattcg ctggatgaca acatcaaaga ggatcagtgt 61200
cagtttctcc ggcttgtatg tctcaaagac aaacttcacc tcagagttga aacgcagggc 61260
atcacggctc gtgatagagc cagagacatc aagaaaatat gccatgtgtg ccagcttgcc 61320
ttcttcaatg tcacgactag gcatgtacat ttcagggtaa cggcgattcg gcctggccca 61380
cgtagtgaac tcttctgaca gttctgtcat gaagtccata agcagttttt cccaaggtac 61440
aacaggcttc aggaatttct tgattacttc cagcacatca ccgggcaggg tgccagcttc 61500
gccagctaac ttggcatgag tgagggcacc cacaaccaaa ttaagctgac cgagaggact 61560
cagcccatca ccagaacaca tatccggctt accacagccc caggcaccac cgggaggtgg 61620
ttttatctgg ttctgtatca gaacatcata gatgtcctca gcagccatat tatcgtactg 61680
gtgatcaagc cacggttgag taccctcaaa ggaataacct gcatagtcca gagcattgtt 61740
gatctccaga tcgcaggcat agttccatgt ccccatgtca cggctaccct gacgggaagc 61800
atgaagtctg gcaacgtgcc aaatctcatg cacaagcacc gtgccacggg tttttcgagg 61860
gatgctcatg aaccactcag ggttccaggc aatactgaca aaatcggtct gtgctgtctt 61920
gatactggtg tcccagtgca taggcagctt gaccatcagg gaaccaagga aagcagcgtt 61980
cttaccagag aatacgtctg cctttactcg gtcgagttca cgggtaagat ctaccattac 62040
ttagccctca gccagctcaa cggataacag gcccatcttt cttttggcag gcttgaaata 62100
ctgcactgca agctgtttgg caggccacag tgctggtgca tagaagccta cctgtttacc 62160
ttcaaaggtg gcgatgtaag cacgatcacc ttcttttttg tcgttcagaa tagtcaggcc 62220
catgatcaat cctcattgag gtattttgcc aactgtacag caacagcagc aaaggttggg 62280
tcacggcgaa gttcgggata cttagccatt gcgaaacgga agaacaggat acgcatatcc 62340
agccccagac ggcctgcata agcagccatt gttgggaagt tcttgatggt catcttgctg 62400
accagaccag atactgtggc ccaggccaag tccagtgagg taggcagacg acagttcagt 62460
gggtctttca tgatctcttc atacttgatg agatccttat agacattaca gaactgatag 62520
aacttggttg caatatcctc accgacagta cctgcataca tcggcagtct gtcttcggtg 62580
acatctttgc caatgatcat acggttgagg aactcaacgg tacgtgggca gcagaatgtc 62640
ttatccgtgt gctttggatc aaagctcatc agatcctctt caaactggct gaaatagcca 62700
atgatacgag gatcgtagtc ctgagcaatt gccacatcac gcaaccagtc gtgataactc 62760
acttccagtt ccaggtgaat cagtcgggac tgagcagccg tggacaggtt attgacgata 62820
gcacggtcgg tggacaggtt tcccgccaga acaatagcca cacgttcatg cagcttcttc 62880
tgacctgtca tacggtctaa gagcagcttg tacgatgcag cttgtgtgtc tttcttggct 62940
gagttgtact catccaggaa cactaaccat ccgtctttac cttccggcag aggcatacct 63000
tcaatcggga acagatcggc aaatggagcg aaacacgcta ctttgccata cggacgttct 63060
tcgaagtaag gcagaccgtt catgtcttcc ggtgggctgg tggacagtcg atgatcgaca 63120
gttgccaggt taaaactttt gctcaggcca ttgcctattg cagacttacc gatgccggga 63180
cttccttgca tgaacggcac cagaccagcc gcaaggattt cctctatcag gctcacggct 63240
tttcgtggtg ttacacgata catacccatg actttctcca gagaataaaa aagccacctt 63300
ctcaggtggc tcggattaaa caacggcagt tgttagtgac aggagatgcg atgacgatta 63360
gaaatcttct tcgcagttcc catacgtgct ggtaaaggac gttcgttgtt accatgacgc 63420
agcttttcgt ggaactcatt ggctgctttg cccaccttga acatgaattg tgtctcggtg 63480
atgcttccag cttccagttg ttccagtaat tgcttaattt ggtacgggcc atttttcatg 63540
gacgcattcc tatgtgagag ggtttcttga gcaggttttt catggcttca aagctctcat 63600
actcgaaggt ttctccacca ttctttctga ggttcttgac cattttatca acctgctgtt 63660
gcagtgacag cagtatattg ctgggatact ctgcaatgac catagacagc agactgcttt 63720
gcagcttctt atccttggtt cggtatgcca gctttgcagc acacatacgc attgcatcat 63780
ccatatccct gccatccaga atggcaaatc cctgagccag agccagtgta gtcactgcat 63840
caggccaatg cccatagaca ctggcacaga tgacttcata ggctgtgaac ttcatagctt 63900
agggatttcc atgatggttt cgcccagctt gttatatggc acaccagcag catccagaat 63960
cagacaaacc ttgcgagtta attcacggtt catcagtggg ctgttgtagt gatccacaat 64020
tttgactggg gtatcaggga aggccagcat ctgatcgaca tagctgaaag cctggcgagt 64080
agtacgacca ctgttgcgag caccattgtt cactgaatca atggcctctt gtaattccaa 64140
atcgttacgg ttcacgatga tttctcctgc ttacgccgat cccttctctt ctggttctgg 64200
agatgtgtca ccagttccag atgctcaggg ttaaaacaat tacgcacatt gcacaggtga 64260
tccacctgac gcttgagcgg aatataccca aagaaatggg tgtaagagac acgatgcaca 64320
gcagaagtaa caccgttaat tgagattcgt ccataaccct taccacgtcc agaaccggat 64380
agtgccccct gccacagatg acagggagac ggtatgccat taacggtata tccggtatct 64440
tcgatcttgg cctgagcata aagacgctgc ttaatttctt cacgcctact cgtcttcatt 64500
atcttcaggc tccggcatcg gttggaaatc cacacccata cccatcaggg tatatacctg 64560
ttcggttagt acctgaattt tatattcaag taccaactca gcagctttct gattaatata 64620
gaggggctgt gctttatcag caaaatacac tgtgaaaagg tgtttctgct gcgactgata 64680
tttaatttca gttgctaggc tgtgtacctt ttccaacatt tggctggcgc gatgaacatc 64740
agtaacattg atcatacgtt ccccatgaaa taaaggtgaa tggcagtatt caataaacga 64800
ataccgatgt tcatatcttt attctgttgt tccagaatct tggcaatgcc tttgacagca 64860
tcagcatctt tggtttctgg acgcagacgt ttgtaagcct gatacagacc tacgtgtttg 64920
atttgcttac gcaaatcttc cattgttact tcaactgtgc tgaagatcaa tggcacacgt 64980
cccaggaact cagtacgcat accagcatcg cgtaattcac tgatgttatt tatcttctgg 65040
ttcgaatacg caccagcgaa aataaacaga gacttgtcga tacgtaccgg atcatatttg 65100
ccgtagtcag tgagaatgct ggaatactta ctttccaggc aggtcagaaa ttcatcctgt 65160
acctgtgaac ggaagttctc agttttctca ccattggttt gaaatagctt atcgaactca 65220
tctacaaaga tgacgtttgg catattccag tgctcacgca atggacgcag ggctttagac 65280
agagagttac ctgacagacc ttcagcagta agctgggctg cattaatctc gatcatttta 65340
ataccaacct cctcacaggc tttgccaatg aggtaggact taccggagcc gcttggccca 65400
gtaacatgaa agtggggacg gatttcacaa tcggactcga tgaaagtctc aaggatcgta 65460
ccgacctgac gaacgaactt ttcttgctgt gggaatagga acatatttgc ctcttgtgct 65520
ttgcacgctt ctgaatgggt ggaacaacca taaaaaaagc ccaccatttc tggtgggctt 65580
ctcttttcgc cggagcagtg ttaactgagc agaggactgt tcagtacgct tgcaccagcc 65640
ggacgggaaa acaggttcaa cttcagctta atcgcctgac tacacaatcg ctcgatctct 65700
ttccacgttg ccgtgggaac cagaagagga acaacagcgg cagcagcggc cacaatgtag 65760
acggggattt cacgcagaag gaacagagta tcgccaacat aatgcaggcc gacgaagact 65820
gacagaaacg agaggcacat gccccagaga tggcttttac gcatggaatt ttcctgtttg 65880
gattaaaggg ttaacaacca aataaagtgc taacccttta tttattaggc tgctacggtc 65940
acgttgacag taacatcttt ggtgccgttg gtcactacaa cagaggtagt acccgcagcg 66000
actggtttaa cagtcagcac gccattggca atggtcgcag ttgctgttgc agaagctgga 66060
gcagtcttaa tagacagcgt acccagatca gcatcagcag gcactggagc gaatgccaca 66120
gtcttgccgt tggttccgtc agttgccacc gacaggctca gggagcttgg ggttgcagtg 66180
atagaggtca gtgctgctgg ttcagcaggc agcttagact taggtgtctc aggcaccact 66240
tctacgtagc ttttgctctc gatggtgatg ttattaccat ccttcacaat cagcttgtag 66300
ataccagcat cagatgcagc cagcttttct ttgctgaatt tcagtgcagt agcaccagag 66360
atgtcagtga agtcatcagc cgggccacca gcgaattgcc acttgtaagt gtatggggtt 66420
ttaccaccac ctacctgacc ggacagcagc aggtcagaac ccacggcaaa cacaacagtt 66480
tgctgaggtt cgaccaacca gtacagctcc tgcttgatag cagcgttggt tgtggtaatg 66540
ctgatttcct gcatgttgta gataccgttc gggtacttca cacctgtgac aggtggagag 66600
gccagcttgg tcgtatacag caggtcacgc acaccgtgat aaatcacgtt gctatccggg 66660
taggtttcat ccgggtgatc gaactcacca attttagtga agccagttgg agcagctacg 66720
ccagtcagtt caacctggac tgtcttggtg gtcgggttaa ggaaggcttg aagtttcata 66780
aatcctctac ttgaaaatac cagatgaacg ttcaaccact gtggcaccca cactcgttgc 66840
tttcttttct ggttcaggtt gtgacaactc ttcgatttct ctcagtgttg ccaatgttgc 66900
tgcaaggtcg tcaaacttga tggtaatttc tgccatctgt ttaactccgt acccttccag 66960
cagtagtttc actgctgtgt agtatgcaac accagtgcct gttgtaccaa ttaagatgta 67020
tccatcaggc agcgttgcat tgataggctg tagcagcaca gccttatcgg tttcattgta 67080
tgagacattc aggatcatga ttatctccgg tgaaaaaata aggactcccc gaagggagtc 67140
cagttgttat gataaagcat actcggtgtt cagaatatcg tcagccagtg ttggatccag 67200
cttaccaatc tgaacgtcag agttggtcat ctgggacagc atgtgactga gcaggttgcc 67260
cttagccagt tcatacagca tacggttgta ctgcttacgc aggtcattgc catagtgagg 67320
caggcaacgg aaacaatcgt ggttggtgat aacctggaac ggtttcttag gcagagtgtc 67380
cagcagtgct tcaacaactt ctacgtctac cagaccgatg ttgtcatagt ccagatagtc 67440
gcagatacgc agggacagca tacccgtctt cagatacata tcccacaggc ttacaaccat 67500
gtcgtaatca gcatctttga caggctgtat tttgtagccg cctttgcttt ctgcaatcat 67560
acggcgaacg ttacggatca gttccatgtc atacatgcaa cgacgaatca tctcacgtac 67620
tacataaccg tcgatactgt gagtgccatt ggcacccagt gaacggcctg actcggtagc 67680
ccggttaacc ttacgatagg tgtcatacgg tgcattgagg aagtgaacag tctctgtctc 67740
ttcatccatt accttgactt taacgtggaa caggtcaggc agagtccagt tgtgctctgt 67800
tgcttctgga tcccagatgt ccaggaatgc tgagttcagt tcccatacag caggagctga 67860
ttcattcatg gtgtcctgga aggtgtaata cagttttcct tcaccgaata ccttcttcgg 67920
catagcctgt gaaccataca gagaagtcat gatgccttgc ttacagtcat cacgttcaat 67980
ctgaccagct tcaccaatgg tagtgaccat gcgatcatag atgacggtat aaccgtcaat 68040
acgcagtgcc tctgcatcgt caccgaatac cggaacaacg ttgcacagtt cagcagcttt 68100
acggtcgcca gtcagacaag ccagaatctg cataccggat gctgttgcat ccagtgagat 68160
tgggtagcca attggcttac cctcacgagc atcacgatac gcctgcatac cagcaaagaa 68220
cattgcaggt gagtcagcct gttcgatcag agagtcgagc tggtgctcgt tctcattgaa 68280
ccaggcaaga cgctcgttcc atttcttctt gtccagacca aaggagtttg ctacgtcaat 68340
ctttaaatat tcgataccgt tgaattgctg catatatgcc tcttgcaatt agggttgatt 68400
agtgaaggtt ctttttggac aggtgctgca tcatctctgc gaacgtttgg tcagcaggct 68460
gattgtcagc ttttctttct ggttcacgtt gatgttcaat catgtgctgt agcacctcga 68520
tgagtgcttc agtctcttca acatgatcag atagacagac cttaacagtc tgcccggtag 68580
cagcatcctg agtctggaag atgacaacgc ctttggcgtc taccatcaat attccacgct 68640
cacctaccag tacacattca ggacgaaatt cgtattcatc ttcaggcttc atcggttact 68700
acctctttat cagtaaactc aagcactgct ttgttccacg gagtgccttg ataggttgca 68760
tggtggccct gacaatacgt tcttccacgc ttgtcatagc gattagtgaa atagaactcg 68820
ttaccttcag aagttaacaa gcccataatg tcttttgcat gggtgtcgta cttctcaaaa 68880
gcacgtacac gcttctcata gtcttcctta gactcgccat ctttggcttt gtctaagtta 68940
cgccatgagt tcttcacaag agcagcagta ttcatattga aactgaatgc aatcttgttg 69000
atacggttca gatgatccag acacacatca ttgttgtgat ggttgttctt cagaatcact 69060
gagcagtccc gtgccagata gcctgactct ttgttagact tgatctctac tggcttaatg 69120
accattggta atggataaga gaagcgatca atctctaact ggacatcacg actaacggtg 69180
tagatgacaa taaatgtctt cagttgtggg ttccagtcga tcaaatcctt acttgcacac 69240
aatagcagct tatcagctac ctcttgtgca gttggataga agtgtcggac tgttcctaac 69300
agggttggca gatcagcacg cttgtgcaat gccatttgag tcatgacagc aaggccaaac 69360
tcaacatcaa taccttcttg ttccatgtaa ccaacaaagt ttacagtggc acagttacga 69420
aactcttcag tgatacgagg tagagtctgg ttcttatcaa acagtttctc taacagcatc 69480
tgatgtgcaa acatagtaga catcgcttct tcctctaaga taattctaac ggttagtgtg 69540
aaagtaaatc attactgctt tgccaggtga atacggcccg tcacttgctc ggtttgctgc 69600
accaacacga acaacgattt tgataacatc agtttctttg cgaacccaat cagacttctt 69660
gcctcggtac atatcctcat caacttcaac acgaagatga ccgtcaatgt gcccagcctg 69720
agtacgcttc ttgatcagat gctgaaggtt ggagtaccaa tgatggaacg ttcttcctct 69780
ggttctaacc tgagcactat gcagttcctg aaggctgctc attggtttcc accttgatat 69840
aagtgcgagc acagtagata gactggttca gttgttcttc atcaagcagc actgccttga 69900
tctcttcgtc agtcttgcca gcagcaatag ctgtttcaat catctgaatg cgagcattca 69960
ggtatcgttg ccagatagtg tccagcttgt tcattcgaaa gtaccccagt aagttacgtc 70020
atcgcccagg aatggacgcc atgcttcatc aaactgacag ttcgatggag cgtctttgaa 70080
cattggtgca atgtccttgt ctttcagacc agccaggcca caaccaatac gagtgacagt 70140
aaatgtcagc tttttacgac cagcagcata ggcaaggaac cctttcacat acgcttcaat 70200
ggttgccagt ggcagcgtat attcaatgtt cttgtctttg gttgggatag caaagctctg 70260
accaaagtga ccatagcttg agccataacg agcaccgtgc tttttatatg cttctttcgc 70320
agcaccagca ccgtgaatac caccttcatt acttccgaac acaaatactt tagccatttt 70380
tgattttctc gattgcgtct aacagacctt gtttacgacc ttcctcgaaa gagagtttct 70440
tttcttggtt caggtcacga cgatcattgg aaccagcagc gtatagctcc tgattaacag 70500
tgagttgttt tattttttga ataacctggt tatagggaca ggctttatcc aacttcagca 70560
ttacctttat ttgctcaaca aaggcatcat gctttggtcg tctacttaat gcagcactga 70620
gttcagcatt agcctgttca gcttttgtag cacgagcacg atagtcaatt gtcattcagt 70680
gcctcgacaa tagtgtccat atactcttcc tgtgcagcat ggtgcatttc accatttaac 70740
tgaacaatgg cgaaccactt accatcgtcc ataatacgat agaaattggc atcaccgtgt 70800
tcgtgccagg tataacgttg cttctctctg aaagacgcaa caaataccaa tacaatcaca 70860
aacaccagaa aaacaattaa cccgacataa atgagattat tcatttagag cctcttcaat 70920
tagtttacgt ataactgcac cgtcagcttc agagccaact aacacagcct caccatcaca 70980
cgcgaagcgt gcaattcggt taagctctgc acatacgaca atatcgttgt tggctatacg 71040
atgtttcaac caggcttcat atgctaatgc acattcttcc ttggtaatac gatggctaat 71100
accgaatgga ttagctattt gagcaggctc atgtatacga aatacattct cacctgcccg 71160
tgctttagat attgggatta cagtaatcat ataaaacttt ccttaataca tcggcaatga 71220
cattgccatg acaagccttc ggagcacaaa aacaaattaa cgtcagttcc ttctcatcta 71280
ttagtttgta tgccagcctg ttcagttcag caataatggt tggctcttgc atatcaatgc 71340
acttagtcaa ccagttacga tagccagcaa tagcttgctc tctgtcctga tcaccatgaa 71400
caacaaatgg attacccatt ggagagccac ggcctatata ttctcctttg gttccatgat 71460
gtttattacc gatagtaatg cgatactcca ttacctcatc cattttggct gagtgtagtt 71520
tctgttgctg tggagtacgg caattagcac acaggttatc ccaggtgctt ttatagccct 71580
tcttacattt gcactgcata ttagctccag attaaaaaag ctcccttatt gggagccttt 71640
cttggatacg tggaatggga acactggctt acgattgccc cattgggcca tcataatagc 71700
gtgagcacgt tcatcactat tatcgaggaa caccacgaca atatcgactt ccggcaattc 71760
atccactact gtgactttca acccagcttc ttcgagcact ggattaatag tcgcttcaac 71820
gcctggtgcg ttctgagtga taacctcgaa ctctggtggc aatgaaccat taccaaacag 71880
atattcgaga ttcttcatca acatgtcagc atcagtgatc cagggatcgc ccgtgattat 71940
tactgttttc atcagttacc ttaaaatcaa ttctaacaac acgcatctct tctttcttac 72000
gagatgcaac cggaacagct tccataccta cgacgacgat atagctgcga ccaccatatt 72060
cgtcttctga ttcggtatca gttacctgtt catgtttacc acgcagccat tgcacaagtg 72120
ctcttttggc tttgtcctct gtttcaaaca accgaggaat accatcttcc cttggctcaa 72180
cctgagtata accagtacgt cgaactgttc ttggttcagg tatgaaatag cctgttggag 72240
tatgctgaat agcccaataa gatttcatat atacctcaat ataaacgcga gcgtttgcag 72300
ggcttgccct gcaataagcg agatgttaga ccagatgaat ctctataacc aaatgtacct 72360
gttgaacagg atcactttta gagatagttg ttgatgtacc atctttgata ttggtacaga 72420
gacagtaacc actttgatac tcatgttgac tcattacata taagcaattg aggaacatga 72480
agtgatcacc gttctttaaa tcacgtaatt gaacgagatc aatattacgt ttgtctctga 72540
tttcaattgt catctttatg cctgccattt attcggatag acaggtcacg ttgtagagaa 72600
cgtttcagtt catcttcacg cacacctgcc aatattttct tttgttgtat gggatcataa 72660
cgtctctgca atatacgaga gcatttacgg tgaacccgtt tacttcttgg ttcaccacat 72720
atttcacata cagcgtattc acggtttaac agcatatttc accacgtagc acggcttatt 72780
cagcctatcc aaagtgtcta tcatatgctt agtaccacgg cttgagccat cccaaaatgc 72840
tacgcctata tcagcaactt gtgccatttc agtatttctc acgaatccag cacgtttgcc 72900
cagaccatcc cagtctgccc aatactcgtg gatcgtattt ccaatatctt tgaagcacgc 72960
atatgcagtc atatctgcac cccgtgccat accacaaact aattcacaat cactgcgaat 73020
cactccttcg gataacaatt cgttgagcac gcctatcatc caggcactgt cctcgaatgt 73080
cctcccaccg aataccacaa ttttctgggc cataggataa ccaccatgta atgttgattc 73140
ctgtctctgg ttcaaagtca gggattttag atttgatcca cgcaacacgt ttttcgtttt 73200
cgtagatctt tccagcgtat gcttcttgcc tgaagtcacc accaccaatg ttaaatggat 73260
agtctgcatt caggccatca tctttgaaca tgtggtacag gtctgaataa accatcctct 73320
taccagcagc atctataccc atacgagtac agaattctgt tagagcaaca cacagaccat 73380
aacggttttt gatgtgttta gtttcctgtg ctccttcaaa tacccactgc gaatagactt 73440
gcaggaacag tttaataatc gggttcattt atttgatcca tgtacatgaa tacctgaaca 73500
accttcatat cttctttgat acgaggcacc actggacttg ttacttccag accatcatcg 73560
taatgattgc gatgcacacc agcgagccac tgagtcaaag cacgctttgc agtatcttca 73620
ctgaggaata gtcttggagt agccattgtc tttctctgcc tggcaggatc atcaacaaca 73680
tcaagctgag tatgaccata accacaaggc cactgtctta gcagttttct tgttggcagg 73740
tgtaagatgc cccacagagc atcatgatta atatcttcac aggccacctt tcattacccc 73800
attaatattc tcttcctgga tccagatttc atcattgcat ttcagcagat gataacgagt 73860
gagcaccaaa tcctgattga tagtgcaacg gattggatgg cccagttctt cgaccttcag 73920
ccagaacttt tcagttctgc cattggcaca ctcaacacca atcttcacga agtcacctac 73980
tttgaggttc ttcagagact gtggtgtagc aggcacagct tcacgaggaa gcatggtatg 74040
gaactgtttc agcatggtat atgacattta gggtgtcctt agtaatttga gtatttctgg 74100
ctactttggt gtttagatag tgtctatctc aaccgttaaa aaagagaacc cacataagcg 74160
tggattctct tctaatataa ctctaactgt tagaacagtt tgcgagcaaa tggattgctt 74220
gaagcgtcta ctttgacctc ttcgttgttg gtacgacgaa gttgaatttg cagattaaca 74280
atctgttctt caccaggtgc catagactgt gcagcttcca taagctgagt cagtaaatcg 74340
ttacgtgcag cctggaacat gttccagtct tggttcttgc ctttgacaac aagttgctca 74400
atgttgtcga gtggaatacc agcaggcagt gatacgaaac gagtttcgtt ctgaccttct 74460
gcattaggca cttccacttc ataacctacg ttaagccaga actggcttgc aggacgctgc 74520
tctttatcag ttgcagcatt gtttttctga ccgaatgatt ttggtaagtc gatagccatg 74580
atttttctct ccagagagtt tttgatttag ggattattcc caatacacgc gaagcgtgtt 74640
gttaattacg agtagcttgt tcagtagatt cactgtcgcc taacagtgaa cgtaccatcc 74700
atagcagagc tgacagtagg atggcaatga catctgagta aggactcaaa tggttgatga 74760
catgaagcat gtcagccata ccatagatga agcagagcat tgatagcagt gtgatgagta 74820
ccttaaacat atgtctatac ctatccatcc agttaaaggt gttaagccct attgctaggg 74880
cttaggtgtt atttagctgc gagtacagca gccagacgtt cctgatttgc tttgaataaa 74940
tcagatgtac caggattagc ttccaggtaa tctttaatac cctgctgacg ttgagtgtca 75000
gccagagcag tttcttcgat gagctgttca gtacgtgaag actgttccag tttcatacgg 75060
atacgctgag tttcagcagc attggtgacg aatgcgtcaa ccataccaac agatttggtt 75120
actacattca gagtggtaga tacagtgtta gcagcatcta ctacagtacc catgatgtta 75180
ccgaatgcga gacgagatga agacatgata gaactcctgg ttaatatatg aatgcaccat 75240
tgcatccaga ccacgcgaag cgtgggtgta tagtgtatgc agttggtgta attaaccggg 75300
ggggggg 75307
Claims (20)
- 에르위니아 아밀로보라(Erwinia amylovora) 및 에르위니아 파이리폴리아(Erwinia pyrifoliae)로 이루어진 군에서 선택된 하나 이상의 균에 특이적인 용균활성을 갖는, 기탁번호 KACC 97038P인 박테리오파지.
- 제1항에 있어서, 상기 박테리오파지는 에르위니아 아밀로보라(Erwinia amylovora)에 특이적인 용균활성을 갖는, 박테리오파지.
- 제1항에 있어서, 상기 박테리오파지는 서열번호 1의 염기서열을 갖는 것인 박테리오파지.
- 제1항에 있어서, 상기 박테리오파지는 포도비리대 과(Podoviridae family)인 것인 박테리오파지.
- 제1항에 있어서, 상기 박테리오파지는 30℃ 내지 70℃에서 활성을 갖는 것인 박테리오파지.
- 제5항에 있어서, 상기 박테리오파지는 40℃ 내지 60℃에서 활성을 갖는 것인 박테리오파지.
- 제1항에 있어서, 상기 박테리오파지는 pH 3 내지 12에서 활성을 갖는 것인 박테리오파지.
- 제7항에 있어서, 상기 박테리오파지는 pH 4 내지 11에서 활성을 갖는 것인 박테리오파지.
- 제1항의 박테리오파지를 유효성분으로 포함하는 농약 조성물.
- 제9항에 있어서, 상기 박테리오파지는 과수화상병(fire blight) 및 과수검은가지마름병으로 이루어진 군에서 선택된 하나 이상의 질병의 예방 또는 치료에 사용되는 것인 농약 조성물.
- 제9항에 있어서, 상기 농약 조성물은 부형제를 더 포함하는 것인 농약 조성물.
- 제11항에 있어서, 상기 부형제는 계면활성제 또는 증량제인 것인 농약 조성물.
- 제9항에 있어서, 상기 농약 조성물은 수화제, 입상수화제, 액상수화제, 액제, 수용제, 수용성입제 및 캡슐화제로 이루어진 군에서 선택된 하나 이상의 형태인 것인 농약 조성물.
- 제1항의 박테리오파지를 유효성분으로 포함하는 항생용 조성물.
- 제1항의 박테리오파지를 유효성분으로 포함하는 소독제.
- 제1항의 박테리오파지를 유효성분으로 포함하는 세척제.
- 제1항의 박테리오파지를 사용하여 과수화상병(fire blight) 및 과수검은가지마름병으로 이루어진 군에서 선택된 하나 이상의 질병을 방제하는 방법.
- 제17항에 있어서, 상기 과수화상병은 에르위니아 아밀로보라 (Erwinia amylovora)에 의해 유발되는 것이고, 상기 과수검은가지마름병은 에르위니아 파이리폴리아(Erwinia pyrifoliae)에 의해 유발되는 것인, 과수화상병을 방제하는 방법.
- 제1항에 따른 박테리오파지의, 과수화상병(fire blight) 및 과수검은가지마름병으로 이루어진 군에서 선택된 하나 이상의 질병의 예방 또는 치료에 사용하기 위한 용도.
- 제1항에 따른 박테리오파지의, 과수화상병(fire blight) 및 과수검은가지마름병으로 이루어진 군에서 선택된 하나 이상의 질병의 예방 또는 치료용 농약 조성물의 제조에 사용하기 위한 용도.
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