KR102037387B1 - 신규한 이미페넴 내성 녹농균 특이 박테리오파지 pa14 및 이를 포함하는 항균 조성물 - Google Patents

신규한 이미페넴 내성 녹농균 특이 박테리오파지 pa14 및 이를 포함하는 항균 조성물 Download PDF

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KR102037387B1
KR102037387B1 KR1020170180963A KR20170180963A KR102037387B1 KR 102037387 B1 KR102037387 B1 KR 102037387B1 KR 1020170180963 A KR1020170180963 A KR 1020170180963A KR 20170180963 A KR20170180963 A KR 20170180963A KR 102037387 B1 KR102037387 B1 KR 102037387B1
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pseudomonas aeruginosa
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김영주
연영은
한범구
김현일
박철세
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Abstract

본 발명은 항생제 내성 녹농균, 특히 이미페넴 내성 녹농균(Imipenem Resistant Pseudomonas aeruginosa, IRPA)에 특이적인 사멸능을 갖는 신규 박테리오파지 PA14, 상기 박테리오파지를 포함하는 항생용 조성물, 사료 첨가용 조성물, 사료, 소독제 또는 세척제 및 상기 박테리오파지를 인간을 제외한 개체에 투여하는 단계를 포함하는 이미페넴 내성 녹농균에 의한 감염성 질병의 예방 또는 치료 방법에 관한 것이다. 본 발명의 박테리오파지 PA14를 이용한 이미페넴 내성 녹농균에 의한 감염성 질병의 예방 또는 치료 방법은 기존의 항생제 등의 화학물질에 비해 녹농균, 특히 항생제 내성 녹농균에 대한 특이성이 매우 높고, 상기 박테리오파지 PA14는 녹농균을 감염시켜 녹농균 내에서 증식함으로써 용균 활성이 우수하고, 녹농균 사멸능이 우수한 장점을 가지고 있다. 또한 본 발명의 박테리오파지 PA14는 사람, 동물, 식물 등 세균 외의 다른 숙주에는 감염되지 않으므로, 항생제의 오남용으로 인한 항생제 내성균의 문제점, 식품 내의 항생제의 잔류 문제, 광범위한 숙주범위의 문제점을 해결할 수 있는 장점이 있다. 따라서, 본 발명의 박테리오파지 PA14는 이미페넴 내성 녹농균에 의한 감염성 질병의 예방 또는 치료, 항생용 조성물, 사료 첨가용 조성물, 사료, 소독제, 또는 세척제 분야에서 다양하게 사용될 수 있다.

Description

신규한 이미페넴 내성 녹농균 특이 박테리오파지 PA14 및 이를 포함하는 항균 조성물{Novel Imipenem Resistant Pseudomonas aeruginosa specific bacteriophage PA14 and antibacterial composition comprising the same}
본 발명은 항생제 내성 녹농균, 특히 이미페넴 내성 녹농균(Imipenem Resistant Pseudomonas aeruginosa, IRPA)에 특이적인 사멸능을 갖는 신규 박테리오파지 PA14, 상기 박테리오파지를 포함하는 항생용 조성물, 사료 첨가용 조성물, 사료, 소독제 또는 세척제 및 상기 박테리오파지를 인간을 제외한 개체에 투여하는 단계를 포함하는 이미페넴 내성 녹농균에 의한 감염성 질병의 예방 또는 치료 방법에 관한 것이다.
녹농균(Pseudomonas aeruginosa)은 Pseudomonas속에 속하는 그람음성의 호기성 간균으로 건강한 사람의 피부, 장관에 존재하며 토양이나 물 등의 환경에서도 쉽게 분류되는 상재균이다. 녹농균은 물 환경에서도 증식할 수 있고, 적당한 유기물질이 있는 물의 표면에서도 증식하기 때문에 싱크대나 샤워기, 온천탕 등의 습한 환경에서 발견된다. 주 감염원은 오염된 물이나 오염된 외과용 수술도구 등이며, 병원감염의 주요 병원체이다. 녹농균은 청녹색의 색소인 녹농소(pyocyanin)를 생산하여 화농증에서 볼 수 있는 녹색증의 원인이 된다. 또한 녹농균은 기회적 병원균으로, 호흡기, 소화-배설기관, 화상부위, 상처 등을 통해 감염되며 병원 내에서 특히 면역력이 저하된 환자에게 감염을 일으키기도 한다. 녹농균은 패혈증, 전신감염, 만성기도감염증, 췌낭포성 섬유증 등의 난치성 감염을 일으키며 소독제나 항생제에 잘 죽지 않는 독성이 강한 병원균이다.
병원 입원 환자에서 녹농균에 의한 패혈증이 중요한 문제로 대두된다. 신생아 패혈증의 원인균에 대한 연구보고서에 따르면, 녹농균은 전체 혈액배양 분리주의 5.9%에 해당되었다. 또한 병원감염에 의한 폐렴의 주요 원인균으로 중환자실 내 병원획득 폐렴의 원인균 조사에서 녹농균은 33%의 가장 높은 빈도를 보였고, 요로감염증의 주요 원인균 조사에서 병원 입원 환자와 외래환자의 녹농균 분리빈도는 각각 10%와 5.8%에 해당하여 녹농균 감염에 의한 요로감염증이 증가하고 있음을 보여주고 있다. 또한 감염성 각막염의 역학조사 결과에 따르면 세균각막염의 가장 흔한 원인균은 녹농균으로 조사되었으며, 국내 화상환자의 상처부위 배양시 녹농균이 24.7%로 가장 높은 분리 빈도를 나타내었다(질병관리본부, 감염병실험실진단, 2005년).
다양한 녹농균 감염증의 증가는 항생제 내성 증가와 관련이 있다. 세균 감염증 치료에 항생제가 널리 사용되고 있고 이에 따라 다양한 항생제에 내성을 나타내는 내성세균이 출현하고 있다. 항생제 내성이 특히 문제가 되고 있는 주요 병원균으로는 장구균(Enterococci), 황색포도상구균(Staphylococcus aureus), 폐렴간균(Klebsiella pneumoniae), 아시네토박터 바우마니(Acinetobacter baumannii), 녹농균(Pseudomonas aeruginosa), 엔테로박터(Enterobacter) species가 알려져 있다. 그 중 녹농균은 소독제나 항생제에 저항성이 높아 병원에서 주로 사용하고 있는 항생제에 대해 쉽게 내성을 획득하며, 특효적 치료제가 적어서 중증이 되는 경우가 있다. 항생제를 사용하였을 때 항생제에 감수성이 있는 세균의 발육이 억제되면 녹농균이 상대적으로 증식하여 균교대 현상이 일어난다. 녹농균은 몇가지 항균제에는 고유의 내성을 가지고 있지만, ß-lactam 계 항생제인 세프타지딤(ceftazidime), 세페핌(cefepime) 및 카바페넴(carbapenem) 등의 약제에는 감수성을 보여 녹농균에 의한 감염의 치료제로 사용되고 있다. 그러나 세페핌이나 카바페넴에도 내성을 보이는 다제내성 균주가 증가하고 있다. 3가지 이상의 약제에 내성을 보이는 다제내성 녹농균은 전체 분리 균주 중 20-30%인 것으로 보고되고 있다. 카바페넴계 항생제인 이미페넴에 내성인 녹농균의 상당수가 다제 내성균인 경우가 많아 감염증의 치료제로 선택할 수 있는 항생제가 제한적이다.
한편, 박테리오파지(bacteriophage)는 특정 세균을 감염시켜 감염된 세균의 성장을 억제하고 저해하는 세균 특이적 바이러스를 의미한다. 박테리오파지는 박테리아에 감염(infection)한 후 박테리아 세포 내부에서 증식을 하고, 증식 후 자손 박테리오파지들이 박테리아 밖으로 나올 때 숙주인 박테리아의 세포벽을 파괴하는 방식으로 박테리아를 사멸시키는 능력을 갖고 있다. 박테리오파지의 박테리아 감염 방식은 매우 특이성이 높아서 특정 박테리아에 감염할 수 있는 박테리오파지의 종류는 일부로 한정된다. 즉, 특정 박테리오파지는 특정 범주의 박테리아에만 감염할 수 있고 이로 인하여 특정 박테리오파지는 특정 박테리아만을 사멸시키며 다른 박테리아에는 영향을 주지 않는다. 따라서 최근 세균성 질환의 대처 방안으로 박테리오파지의 활용이 크게 주목을 받고 있다. 자연 친화적 방식의 선호로 인하여 박테리오파지에 대한 관심은 어느 때보다 높다고 할 수 있다. 기존 항생제의 대체 물질로의 개발 가능성이 부각되면서 다시 박테리오파지가 항-박테리아제로 주목을 받고 있다.
이에 본 발명자들은 녹농균(Pseudomonas aeruginosa)에 특이적인 용균활성을 갖는 박테리오파지를 분리하고 분리된 박테리오파지의 형태적 및 유전적 특성을 분석하여 상기 박테리오파지가 항생제 내성 녹농균, 특히 이미페넴 내성 녹농균(Imipenem Resistant Pseudomonas aeruginosa, IRPA)을 선택적으로 사멸시킬 수 있음을 확인함으로써 본 발명을 완성하였다.
본 발명의 목적은 녹농균(Pseudomonas aeruginosa)에 특이적인 사멸능을 갖는, 서열번호 1로 표시되는 염기서열로 이루어진 박테리오파지 PA14를 제공하는 것이다.
본 발명의 또 다른 목적은 상기 박테리오파지 PA14를 포함하는, 항생용 조성물, 사료 첨가용 조성물, 사료, 소독제 또는 세척제를 제공하는 것이다.
본 발명의 또 다른 목적은 상기 박테리오파지 PA14를 인간을 제외한 개체에 투여하는 단계를 포함하는, 이미페넴 내성 녹농균에 의한 감염성 질병의 예방 또는 치료 방법을 제공하는 것이다.
상기 목적을 달성하기 위하여, 본 발명은 녹농균(Pseudomonas aeruginosa)에 특이적인 사멸능을 갖는, 서열번호 1로 표시되는 염기서열로 이루어진 박테리오파지 PA14를 제공한다.
또한, 본 발명은 상기 박테리오파지 PA14를 포함하는, 항생용 조성물을 제공한다.
또한, 본 발명은 상기 박테리오파지 PA14를 포함하는, 사료 첨가용 조성물을 제공한다.
또한, 본 발명은 상기 박테리오파지 PA14를 포함하는, 소독제를 제공한다.
또한, 본 발명은 상기 박테리오파지 PA14를 포함하는, 세척제를 제공한다.
또한, 본 발명은 상기 박테리오파지 PA14를 인간을 제외한 개체에 투여하는 단계를 포함하는, 이미페넴 내성 녹농균에 의한 감염성 질병의 예방 또는 치료 방법을 제공한다.
본 발명의 박테리오파지 PA14를 이용한 이미페넴 내성 녹농균에 의한 감염성 질병의 예방 또는 치료 방법은 기존의 항생제 등의 화학물질에 비해 녹농균, 특히 항생제 내성 녹농균에 대한 특이성이 매우 높고, 상기 박테리오파지 PA14는 녹농균을 감염시켜 녹농균 내에서 증식함으로써 용균 활성이 우수하고, 녹농균 사멸능이 우수한 장점을 가지고 있다. 또한 본 발명의 박테리오파지 PA14는 사람, 동물, 식물 등 세균 외의 다른 숙주에는 감염되지 않으므로, 항생제의 오남용으로 인한 항생제 내성균의 문제점, 식품 내의 항생제의 잔류 문제, 광범위한 숙주범위의 문제점을 해결할 수 있는 장점이 있다. 따라서, 본 발명의 박테리오파지 PA14는 이미페넴 내성 녹농균에 의한 감염성 질병의 예방 또는 치료, 항생용 조성물, 사료 첨가용 조성물, 사료, 소독제, 또는 세척제 분야에서 다양하게 사용될 수 있다.
도 1은 박테리오파지 PA14의 이미페넴 내성 녹농균에 대한 용균반 형성 활성을 확인한 결과를 나타낸 도이다.
도 2는 박테리오파지 PA14 유전자 시퀀싱 분석 결과로 얻은 유전자 맵을 나타낸 도이다.
도 3은 전자 현미경을 통해 박테리오파지 PA14의 형태학적 특성을 확인한 결과를 나타낸 도이다.
도 4는 박테리오파지 PA14의 단백질 패턴을 SDS-PAGE를 통해 확인한 결과를 나타낸 도이다.
이하, 본 발명에 대해 상세히 설명한다.
본 발명은 이미페넴 내성 녹농균에 특이적인 사멸능을 갖는, 서열번호 1로 표시되는 염기서열로 이루어진 박테리오파지 PA14를 제공한다.
본 발명에서, 용어 박테리오파지(bacteriophage)는 특정 세균에 감염하여 해당 세균의 성장을 억제하고 저해하는 세균 특이적 바이러스로, 단일 혹은 이중 사슬의 DNA 또는 RNA를 유전 물질로 포함하는 바이러스를 의미한다.
본 발명에서 특이적인 사멸능을 보이는 녹농균(Pseudomonas aeruginosa)은 다제내성 녹농균(multidrug-resistant Pseudomonas), 카바페넴 내성 녹농균, 키노른 내성 녹농균 또는 아미노글리코시드 내성 녹농균을 포함하며, 바람직하게는 카바페넴 내성 녹농균 중 패혈증, 전신감염, 만성기도 감염증 및 췌낭포성 섬유증 환자에게 난치성 감염을 일으키는 병원성 세균으로 알려져 있는 이미페넴 내성 녹농균(Imipenem Resistant Pseudomonas aeruginosa, IRPA)이나, 이에 제한되지 않는다.
본 발명의 박테리오파지 PA14의 전체 유전자의 크기는 92,732 bp이며, GC함량이 49.4%, 전체 ORFs의 수는 169개이다. 상기 박테리오파지 PA14는 약 140-160 nm의 크기로, 정이십면체의 머리를 가지며 꼬리가 있는 형태인 마이오비리대(Myoviridae)에 속한다. 상기 박테리오파지 PA14의 단백질 패턴 분석 결과 62 kDa, 47 kDa, 35 kDa, 17 kDa 그리고 15 kDa 크기의 단백질을 포함함을 확인하였다. 또한 상기 박테리오파지 PA14는 이미페넴 내성 녹농균에 대한 우수한 감수성을 통한 녹농균 사멸 능력을 가지고 있다.
본 발명의 박테리오파지 PA14는 서열번호 1로 표시되는 염기서열을 전체 유전자의 전체 또는 일부로서 포함할 수 있다. 또한, 본 발명의 박테리오파지 PA14는 서열번호 1로 표시되는 염기서열, 및 상기 염기서열의 기능적 동등물로 이루어질 수 있다. 상기 기능적 동등물이란 염기서열의 변형, 치환의 결과, 상기 서열번호 1로 표시되는 염기서열과 적어도 70% 이상, 바람직하게는 80% 이상, 더욱 바람직하게는 90% 이상, 더더욱 바람직하게는 95% 이상의 서열 상동성을 갖는 것으로, 서열번호 1로 표시되는 염기서열과 실질적으로 동질의 생리활성을 나타내는 서열을 의미한다.
상기와 같은 이미페넴 내성 녹농균 특이적 용균활성은 본 발명의 박테리오파지 PA14를 이미페넴 내성 녹농균에 의한 감염성 질병의 예방 및 치료용 조성물, 및 상기 박테리오파지 PA14를 유효성분으로 포함하는 다양한 제품에 적용이 가능하게 한다.
본 발명의 박테리오파지 PA14는 도축장, 도계장 및 농장 부근의 하수로부터 시료를 채취하여 분리한 박테리오파지로서, 본 발명자는 이를 박테리오파지 PA14로 명명하고 2017년 09월 13일에 한국미생물보존센터에 수탁번호 KFCC11738P로 기탁하였다.
또한, 본 발명은 상기 박테리오파지 PA14를 포함하는, 항생용 조성물을 제공한다.
본 발명에서, 용어 항생용 조성물은 약제 형태로 개체에 제공되어 균을 사멸시킬 수 있는 제제를 의미하며, 방부제, 살균제, 항생제 및 항균제를 총칭하는 것이다.
본 발명의 박테리오파지 PA14는 기존 항생제에 비하여 이미페넴 내성 녹농균에 대한 특이성이 매우 높으므로, 유익균은 죽이지 않고, 특정 병원균만 사멸시킬 수 있고, 약물 내성 내지 저항성을 유도하지 않아, 기존의 항생물질에 비하여 제품수명(life cycling)이 긴 신규 항생제로서 이용될 수 있다.
또한, 본 발명은 상기 박테리오파지 PA14를 포함하는, 사료 첨가용 조성물을 제공한다.
축산, 수산업에서 사용되는 사료 첨가용 항생제는 질병의 예방 목적으로 사용되고 있는데, 예방 목적의 항생제 투여는 내성균 발생 가능성을 높이고 가축에 잔류하는 항생제가 사람에게 전달될 수 있어서 문제이다. 항생제가 육류를 통해 인체에 흡수되면 항생제 내성을 유발해 질병의 확산을 부를 수도 있다. 또한, 사료에 섞어 먹이는 항생제의 종류가 많고 이는 다제 내성균 발생 확률이 높아지는 문제점이 있기 때문에 좀 더 자연 친화적이면서도 기존의 항생제의 사용에서 발생한 문제를 해결할 새로운 사료 첨가용 항생물질로서 본 발명의 상기 박테리오파지 PA14를 이용할 수 있다.
또한, 본 발명은 상기 사료 첨가용 조성물을 포함하는 사료를 제공할 수 있으며, 본 발명의 사료는 박테리오파지를 사료 첨가제 형태로 따로 제조하여 사료에 혼합시키거나, 사료 제조 시 직접 첨가시켜 제조할 수 있다. 본 발명의 사료 내 박테리오파지는 액상 또는 건조 상태일 수 있으며, 바람직하게는 건조된 분말형태이다. 건조방법은 통풍건조, 자연건조, 분무건조 및 동결건조가 가능하지만, 이에 제한되는 것은 아니다. 본 발명의 박테리오파지는 분말형태로 사료 중량의 0.05 내지 10 중량%, 바람직하게는 0.1 내지 2 중량%의 성분비로 혼합될 수 있다. 또한, 상기 사료는 본 발명의 박테리오파지 외에 사료의 보존성을 높일 수 있는 통상의 첨가제들을 추가로 포함할 수 있다.
본 발명의 사료 첨가용 조성물에는 비병원성의 다른 미생물이 추가로 첨가될 수 있다. 첨가될 수 있는 미생물로는 단백질 분해 효소, 지질 분해효소 및 당 전환 효소를 생산할 수 있는 바실러스 서브틸리스(Bacillus subtilis)와 같은 고초균, 소의 위와 같은 혐기적 조건에서 생리적 활성 및 유기물 분해능이 있는 락토바실러스 균주(Lactobacillus sp.), 가축의 체중을 증가시키며 우유의 산유량을 늘리고 사료의 소화 흡수율을 높이는 효과를 보여주는 아스퍼질러스 오리자에(Aspergillus oryzae)와 같은 사상균 및 사카로미세스 세레비지에(Saccharomyces cerevisiae)와 같은 효모로 구성된 군으로부터 선택될 수 있다.
본 발명의 박테리오파지 PA14를 포함하는 사료에는 식물성으로는 곡물류, 근과류, 식품가공 부산물류, 조류, 섬유질류, 제약 부산물류, 유지류, 전분류, 박류, 곡물부산물류 등이 있으며, 동물성으로는 단백질류, 무기물류, 광물성류, 단세포 단백질, 동물성 플랑크톤류, 남은 음식물 등이 있으며 이에 제한되는 것은 아니다.
본 발명의 사료 첨가용 조성물에는 품질 저하를 방지하기 위하여 첨가하는 결착제, 유화제, 보존제 등이 포함될 수 있고, 효용 증대를 위하여 사료에 첨가하는 아미노산제, 비타민제, 효소제, 생균제, 향미제, 비단백태질소화합물, 규산염제, 완충제, 착색제, 추출제, 올리고당 등이 포함될 수 있으며, 그 외에도 사료 혼합제 등을 추가로 포함할 수 있다.
또한, 본 발명은 박테리오파지 PA14를 포함하는, 음용수 첨가제를 제공한다.
본 발명의 음용수 첨가제는 상기 박테리오파지 PA14 또는 이를 포함하는 조성물을 음용수 첨가제 형태로 따로 제조하여 사료 또는 음용수에 혼합하는 방식으로 사용되거나, 음용수 제조 시 직접 첨가하는 방식으로 사용할 수 있다. 상기와 같이 음용수에 혼합하여 공급함으로써 지속적으로 이미페넴 내성 녹농균의 숫자를 감소시킬 수 있는 효과가 있다.
본 발명에서 음용수는 특별히 제한되지 아니하며, 당해 기술 분야에서 통상적으로 사용되는 음용수를 사용할 수 있다.
또한, 본 발명은 상기 박테리오파지 PA14를 포함하는, 소독제를 제공한다.
이미페넴 내성 녹농균에 특이적 사멸능을 갖는 본 발명의 박테리오파지 PA14를 포함하는 소독제는 병원감염을 막기 위한 병원 및 보건용의 소독제로 유용하게 사용될 수 있고 일반 생활 소독제, 식품 및 조리 장소 및 설비의 소독제, 양계장, 축사 등의 건물, 축체, 음수, 깔짚, 난좌, 운반차량, 식기 등의 각종 생육 용품의 소독 등에 사용될 수 있다.
또한, 본 발명은 상기 박테리오파지 PA14를 포함하는, 세척제를 제공한다.
본 발명의 박테리오파지 PA14는 이미페넴 내성 녹농균에 특이적 사멸능을 가지므로, 이미페넴 내성 녹농균에 노출되었거나 노출될 가능성이 있는 개체의 피부 표면 또는 신체 각 부위 등을 세척하는 용도로도 사용될 수 있다.
또한, 본 발명은 상기 박테리오파지 PA14를 인간을 제외한 개체에 투여하는 단계를 포함하는, 이미페넴 내성 녹농균에 의한 감염성 질병의 예방 또는 치료 방법을 제공한다.
본 발명의 박테리오파지 PA14는 이미페넴 내성 녹농균에 특이적인 사멸능을 가지므로, 이미페넴 내성 녹농균에 의한 감염성 질병의 예방 또는 치료에 이용될 수 있다. 보다 구체적으로, 본 발명의 박테리오파지 PA14는 이미페넴 내성 녹농균에 대한 특이적인 사멸능을 가지므로, 상기 이미페넴 내성 녹농균에 의한 감염성 질병의 예방 또는 치료에 이용될 수 있다.
본 발명에서, 이미페넴 내성 녹농균에 의한 감염성 질병은 그 증상으로 피부감염, 욕창, 각막염, 중이염, 심내막염, 폐렴, 균혈증, 수막염 및 뇌농양 등을 포함하나, 이에 제한되는 것은 아니며, 이미페넴 내성 녹농균에 의한 2차 감염을 포함한다.
본 발명에서, 용어 "개체"는 이미페넴 내성 녹농균에 의한 감염성 질병이 발병될 수 있는 모든 개체를 의미하는 것으로 인간을 제외한 포유동물, 가축류 또는 가금류를 포함하나, 이에 제한되는 것은 아니다.
상기 용어 "가축류"는 인간에 의하여 순화, 개량되어 사람과 함께 공동생활을 하는 유용한 동물을 지칭하는 개념으로, 예를 들어, 돼지, 소, 닭, 말, 오리 또는 개 등을 포함하나, 이에 제한되는 것은 아니다.
상기 용어 "가금류"는, 가축 중 조류에 속하는 동물을 총칭하여 이르는 개념으로, 예를 들어, 닭, 오리, 꿩, 메추리, 타조, 거위 또는 칠면조 등을 포함하나, 이에 제한되는 것은 아니다.
본 발명의 방법에서 상기 박테리오파지 PA14 또는 조성물은 약학적 제제의 형태로 동물에게 투여되거나, 가축의 사료 또는 음용수에 혼합하여 이를 섭식시키는 방법을 통해 투여될 수 있다.
본 발명의 방법에서 상기 박테리오파지 PA14 또는 조성물의 투여 경로는 목적 조직에 도달할 수 있는 한 경구 또는 비경구의 다양한 경로를 통하여 투여될 수 있으며, 구체적으로, 구강, 직장, 국소, 정맥 내, 복강 내, 근육 내, 동맥 내, 경피, 비측 내, 흡입 등을 통해 통상적인 방식으로 투여될 수 있다.
본 발명의 방법에 투여되는 상기 박테리오파지 PA14의 적합한 총 1일 사용량은 올바른 의학적 판단범위 내에서 처치의에 의해 결정될 수 있다는 것은 당업자에게 자명한 일이다. 특정 개체에 대한 구체적인 치료적 유효량은 달성하고자 하는 반응의 종류와 정도, 환자의 연령, 체중, 일반 건강 상태, 성별 및 식이, 투여시간, 투여 경로 및 조성물의 분비율, 치료기간, 구체적 조성물과 함께 사용되거나 동시 사용되는 약물을 비롯한 다양한 인자와 의약 분야에 잘 알려진 유사 인자에 따라 다르게 적용하는 것이 바람직하다.
본 명세서에서 달리 정의되지 않은 용어들은 본 발명이 속하는 기술 분야에서 통상적으로 사용되는 의미를 갖는 것이다.
이하, 본 발명을 실시예, 제제예에 의해 상세히 설명한다. 단, 하기 실시예, 제제예는 본 발명을 예시하는 것일 뿐 본 발명의 내용이 하기 실시예, 제제예에 한정되는 것은 아니다.
실시예 1: 신규한 박테리오파지의 분리 및 배양
1.1 박테리오파지의 스크리닝 및 분리
이미페넴 내성 녹농균에 특이적인 박테리오파지를 스크리닝 및 분리하기 위해서 용균반 분석을 수행하였다. 시료는 박테리오파지가 존재할 것으로 예상되는 대전 하수처리장에서 채취하였으며, 박테리오파지 분리에 사용된 이미페넴 내성 녹농균은 아시아태평양 감염연구소에서 분양받은 것을 사용하였다.
구체적으로, 채취한 시료를 균질화 한 후 이미페넴 내성 녹농균과 함께 35℃에서 하룻밤 동안 진탕배양 하였다. 상기 배양액을 4,000 rpm으로 20분간 원심분리한 후, 상등액을 공극(pore) 크기가 0.2 μm인 필터를 이용하여 여과하여 시료 여과액을 얻었다. 상기 여과액을 이용하여 용균반 분석을 통해 대상 시료에 이미페넴 내성 녹농균을 특이적으로 용균할 수 있는 박테리오파지를 선별하였다.
다음으로 이미페넴 내성 녹농균을 특이적으로 용균할 수 있는 박테리오파지를 스크리닝하기 위하여, 이미페넴 내성 녹농균 150 μL를 취해서 멸균된 튜브에 넣고 3 mL의 BHI 탑 아가(top agar) [뇌심장침출액(뇌 침출 솔리드(solids) 12.5 g, 소 심장 침출 솔리드 5.0 g, 프로테오스펩톤 10.0 g, 글루코스 2.0 g, 소듐클로라이드 5 g, 인산나트륨 2.5 g/L) + 0.6% 아가]를 첨가하여 잘 혼합한 후 미리 만들어 둔 2% BHI 아가 플레이트에 중층하였다. 실온에서 30분간 방치한 후 상기 시료 여과액을 각각 10 μL씩 점적하고, 다시 실온에서 30분간 방치한 후 35℃에서 24시간 동안 배양하여 박테리오파지의 유무를 확인하였다.
박테리오파지의 존재를 확인한 시료로부터 박테리오파지를 순수 분리하기 위해서 소프트 아가 오버레이(soft agar overlay)법을 이용하였다. 박테리오파지가 존재하는 것으로 확인된 시료를 식염수로 적절히 희석하여 각 희석단의 시료 희석액 100 μL를 취하고, 대상 세균(이미페넴 내성 녹농균) 배양액 150 μL에 혼합한 후 0.6% BHI 탑 아가 3 mL을 첨가하여 잘 혼합한 뒤, 미리 만들어 둔 2% BHI 아가 플레이트에 중층하여 방치한 후 35℃에서 24시간 배양하였다. 배양한 각 플레이트에서 형성된 용균반을 확인한 후, 이를 선택하여 400 μL의 SM 완충액(NaCl 5.8 g/L; MgSO47H2O 2 g/L; 1M Tris-HCl(pH 7.5) 50 mL)에 현탁하고, 실온에서 4시간 동안 방치하였다. 상기 박테리오파지액 100 μL를 0.6% BHI 탑 아가와 세균 배양액 500 μL와 혼합한 뒤 150 mm 지름의 BHI 플레이트에 분주하여 중층한 후 완전히 용균이 일어날 때까지 35℃에서 배양하였다. 배양이 종료된 후, BHI 플레이트에 15 mL의 SM 완충액을 가하고 실온에서 4시간 동안 천천히 교반하면서 박테리오파지 용액을 회수한 후 4,000 rpm으로 20분간 원심분리하여 상등액만 취하고 이를 0.2 μm 필터로 여과하여 최종 박테리오파지 용액을 회수하였다. 이렇게 얻어진 최종 박테리오파지의 용균반을 확인한 결과를 도 1에 나타내었다.
도 1에 나타낸 바와 같이, 2-3 mm의 크기를 가지는 용균반을 형성하는 박테리오파지를 확인하였고, 상기 박테리오파지는 이미페넴 내성 녹농균에 특이적인 용균능을 갖는 박테리오파지임을 확인하였다.
1.2 박테리오파지의 대량 배양 및 정제
상기 실시예　1.1에서 확인한 이미페넴 내성 녹농균 특이적 박테리오파지를 대량 배양하기 위하여, 1.1에서 회수한 최종 박테리오파지 배양액을 1.0×107 PFU/mL로 희석한 후 전배양된 이미페넴 내성 녹농균 1.0×109 CFU/mL과 혼합하여 MOI(Multiplicity of infection)가 0.01이 되도록 하여 35℃에서 100 rpm으로 18시간 동안 배양하였다. 배양이 종료된 후 배양액 전량을 6,000 rpm으로 30분간 원심분리하여 상등액을 수득하였고, 이를 0.2 μm 필터로 여과하여 최종 박테리오파지 배양액을 회수하였다. 분리된 박테리오파지를 박테리오파지 PA14(Bacteriophage PA14)로 명명하고, 2017년 09월 13일 한국미생물보존센터(Korean Culture Center of Microorganisms, 서울, 한국)에 기탁하고 수탁번호 KFCC11738P를 부여받았다.
실시예 2: 박테리오파지 PA14의 전체 유전자 분석
박테리오파지 PA14의 전체 유전자를 분석하기 위해, 박테리오파지 PA14 배양액에 20 mM EDTA, 50 μg/mL의 프로테나아제 K, 0.5%(w/v) SDS를 가한 후, 50℃에서 1시간 동안 정치하였다. 동량의 페놀-클로로포름-이소프로필 알코올 (25:24:1)과 혼합한 후 실온에서 12,000 rpm으로 10분간 원심분리하여 상등액을 회수하였다. 회수된 상등액을 동일 부피의 페놀-클로로포름-이소프로필 알코올(25:24:1)과 혼합하여 실온에서 12,000 rpm으로 10분간 원심분리한 후 상등액을 회수하고, 상기 상등액에 3M 소듐 아세테이트를 전체 부피의 10%(v/v)가 되도록 가한 후 혼합하였다. 여기에 2배 부피의 차가운 95% 에탄올을 가하여 혼합한 뒤 -20℃에서 1시간 동안 정치하였다. 반응이 끝난 후 0℃에서 10분간 12,000 rpm으로 원심분리하여 침전물을 획득하였고, 차가운 70% 에탄올로 2회 세척한 뒤 에탄올을 완전히 제거하여 DNA 펠렛을 회수하였다. 회수한 펠렛을 최종 부피가 50 μL가 되도록 TE 완충액(Tris-EDTA, pH8.0)에 용해시킨 후 DNA 농도를 측정하였다. 전체 유전자 분석을 위해 PacBioRSII 를 이용하여 유전자 시퀀싱을 수행하였다(마크로젠, 한국). 상기 시퀀싱 분석을 수행한 결과로 얻은 박테리오파지 PA14의 유전자 맵을 도 2에 나타내었다.
도 2에 나타낸 바와 같이, 박테리오파지 PA14의 전체 유전자의 크기는 92,327 bp이며, GC함량이 49.4%, 전체 ORFs의 수는 169개임을 확인하였다. 상기 분석한 박테리오파지 PA14의 전체 유전자 서열을 서열번호 1로 나타내었다.
실시예 3: 박테리오파지 PA14의 형태학적 특성
박테리오파지 PA14의 형태학적 특성을 알아보기 위해, 배양액을 0.01% 젤라틴 용액에 희석하여 2.5% 글루타르알데하이드(glutaraldehyde) 용액으로 고정하였다. 이를 Carbon-coated mica plate(ca. 2.5 x 2.5 mm)에 적가한 후, 10분간 적응시켜 멸균증류수로 세척하였다. 이를 구리 격자(copper grid)에 끼워 2% 우라닐 아세테이트(Uranyl acetate)에서 30-60초간 염색하고 건조시킨 후, 투과전자현미경(Tecnai G2 Spirit Twin, Bio-Transmission electron microscope, 120 kV, 120,000~400,000)으로 관찰하였다. 그 결과를 도 3에 나타내었다.
도 3에 나타낸 바와 같이, 박테리오파지 PA14는 약 140-160 nm의 크기로, 정이십면체의 머리를 가지며 꼬리가 있는 형태인 마이오비리대(Myoviridae)에 속함을 확인하였다.
실시예 4: 박테리오파지 PA14의 단백질 패턴 분석
박테리오파지 PA14의 단백질 패턴을 분석하기 위해, 1.0×1010 PFU/mL로 준비된 박테리오파지 PA14 40 μL를 10 μL의 5X 로딩 완충액과 혼합하고, 10분간 끓인 다음 12.5% SDS-PAGE를 수행하였다. SDS-PAGE 수행 후 단백질 전기영동 결과를 도 4에 나타내었다.
도 4에 나타낸 바와 같이, 박테리오파지 PA14는 62 kDa, 47 kDa, 35 kDa, 17 kDa 그리고 15 kDa 크기의 단백질을 포함함을 확인하였다.
실시예 5: 박테리오파지 PA14의 다양한 세균에 대한 감염성 조사
박테리오파지 PA14의 다양한 세균에 대한 감염성을 조사하였다.
우선, 박테리오파지 PA14의 이미페넴 내성 녹농균에 대한 용균 활성을 확인하기 위하여, 아시아태평양 감염연구소에서 분양받은 이미페넴 내성 녹농균을 대상으로 소프트 아가 오버레이법을 수행하였다. 그 결과를 표 1에 나타내었다.
Figure 112017129791214-pat00001
(+; 용균활성 있음, -; 용균활성 없음)
상기 표 1에 나타낸 바와 같이, 본 발명의 박테리오파지 PA14는 이미페넴 내성 녹농균에 대해 높은 감수성을 가지는 것을 확인하였다.
다음으로, 박테리오파지 PA14가 이미페넴 내성 녹농균이 아닌 다른 다양한 세균에 대해서 용균활성을 나타내는지 확인하기 위하여 ㈜옵티팜에서 분리하여 보유하고 있는 균주와 미생물 자원센터 등에서 분양받은 균주를 대상으로 소프트 아가 오버레이법을 통해서 감염성을 확인하였다. 그 결과를 표 2에 나타내었다.
Figure 112017129791214-pat00002
(+; 용균활성 있음, -; 용균활성 없음)
표 2에 나타낸 바와 같이, 본 발명의 박테리오파지 PA14는 이미페넴 내성 녹농균에 대해서만 용균성을 가지나, 이미페넴 내성 녹농균 외에 다른 속인 Salmonella 종이나 Bacillus, Lactobacillus plantarum 등의 균주에 대해서는 용균활성이 없는 것을 확인하였다.
따라서, 본 발명의 박테리오파지 PA14는 이미페넴 내성 녹농균에 특이적으로 용균활성을 나타내는 박테리오파지임을 확인하였다.
실시예 6: 박테리오파지 PA14의 세균 사멸 능력
박테리오파지 PA14의 이미페넴 내성 녹농균에 대한 세균 사멸 능력을 확인하기 위하여, 1시간 단위로 흡광도 600 nm에서 세균의 배양 상태를 관찰하였다. 600 nm에서 흡광도가 0.5 정도 되는 이미페넴 내성 녹농균 배양액을 10 mL 준비한 후, 세균 배양액에 농도가 1.0x1010 PFU/mL 되는 박테리오파지액을 1 mL 넣어 MOI 10으로 접종한 것을 실험군 1로 결정하였다. 또한, 1.0x109 PFU/mL 농도의 박테리오파지액을 1 mL 넣어 MOI 1로 접종한 것을 실험군 2로 결정하였으며, 박테리오파지액을 넣지 않은 시료를 대조군으로 하였다. 이후 4시간 동안 배양하면서 1시간 단위로 흡광도 600 nm에서 세균의 배양 상태를 관찰한 결과를 표 3에 나타내었다.
Figure 112017129791214-pat00003
표 3에 나타난 바와 같이, 박테리오파지 PA14를 첨가하지 않은 대조군의 경우 4시간 후 600 nm에서 흡광도가 1.21로 나타나 녹농균이 지속적으로 잘 성장한 것을 확인하였다. 반면, 박테리오파지 PA14를 첨가한 실험군 1 및 2의 경우 4시간 경과했을 때 600 nm에서 흡광도가 각각 0.22와 0.27로 배양 시작단계보다 감소한 것을 확인하였다. 따라서, 박테리오파지 PA14가 이미페넴 내성 녹농균에 대하여 증식을 억제능을 보여줄 뿐 아니라 우수한 세균 사멸능을 나타내는 박테리오파지임을 확인하였다.
상기 실험으로부터 박테리오파지 PA14는 항생제 내성 녹농균, 특히 이미페넴 내성 녹농균에 대한 특이성이 매우 높고, 녹농균 내에서 증식함으로써 용균 활성이 우수하고 녹농균 사멸능이 우수하다는 장점을 가지고 있음을 확인하였다. 또한 본 발명의 박테리오파지 PA14는 사람, 동물, 식물 등 세균 외의 다른 숙주에는 감염되지 않으므로, 항생제의 오남용으로 인한 항생제 내성균의 문제점, 식품 내의 항생제의 잔류 문제, 광범위한 숙주범위의 문제점을 해결할 수 있는 장점이 있다. 따라서, 본 발명의 박테리오파지 PA14는 이미페넴 내성 녹농균에 의한 감염성 질병의 인간을 제외한 개체의 예방 또는 치료방법, 항생용 조성물, 사료 첨가용 조성물, 사료, 소독제, 또는 세척제 분야에서 다양하게 사용될 수 있다.
비록 본 발명이 상기에 언급된 바람직한 실시예로서 설명되었으나, 발명의 요지와 범위로부터 벗어남이 없이 다양한 수정이나 변형을 하는 것이 가능하다. 또한 첨부된 청구 범위는 본 발명의 요지에 속하는 이러한 수정이나 변형을 포함한다.
이하 본 발명의 박테리오파지 PA14를 포함하는 감염성 질병의 예방 또는 치료용 약학적 조성물의 제제예를 설명하나, 본 발명을 한정하고자 함이 아니고 단지 이를 구체적으로 설명하고자 함이다.
제제예 1: 의약품의 제조
1.1 주사제의 제조
박테리오파지 PA14 1 × 106 PFU/mL
주사용 멸균 증류수 적량
pH 조절제 적량
통상의 주사제의 제조방법에 따라 1앰플당(2 mL) 상기의 성분 함량으로 제조한다.
1.2 액제의 제조
박테리오파지 PA14 1 × 106 PFU/mL
설탕 20 g
이성화당 20 g
레몬향 적량
정제수를 가하여 전체 1,000 mL로 맞추었다. 통상의 액제의 제조방법에 따라 상기의 성분을 혼합한 다음, 갈색병에 충전하고 멸균시켜 액제를 제조한다.
1.3 정제의 제조
박테리오파지 PA14 1 × 106 PFU/mL
옥수수전분 100 mg
유당 100 mg
스테아린산 마그네슘 2 mg
상기의 성분들을 혼합한 후 통상의 정제의 제조방법에 따라서 타정하여 정제를 제조한다.
한국미생물보존센터(국내) KFCC11738P 20170913
SEQUENCE LISTING <110> Optipharm.CO.,LTD <120> Novel Imipenem Resistant Pseudomonas aeruginosa specific bacteriophage PA14 and antibacterial composition comprising the same <130> 1-61P <160> 1 <170> PatentIn version 3.2 <210> 1 <211> 92732 <212> DNA <213> Direct input <400> 1 ctagaacagg tgcagtataa gcacgatgcg agtgacattg taccacagtt tttcgaactg 60 ctatacgtga acgttgactt ggaggatgac gtagagtgaa acaatatgac agagtgtata 120 aactaacgct cggtaacact gaatccgggc aaggtgtaga gattacaaac ctccaccctg 180 acggaagttt gaacagagag ggacttcagt tccggtttga tatctctaaa agttcagata 240 acaagaagag cggaaactcg gcgactgttg agatatacaa tctgtctatt gccactctga 300 acattcttga aactgagtat ctgacgtgcc gactagaagt tggttataag gaaatgggaa 360 cttctgttgt gcttgatggc aacgtggttg aaacttcgac tagaaagagt ggtaacgatt 420 atgtcactca gcttattcta ggtgaaggat atacagcact aacagagacc aagctgaagg 480 gcacagtatc tccgggcaaa actgtaaagg atgttatcga agaaattcgt cttcaaatgc 540 cgggagtgga cagaggagct tatacaggcc tcaattgcaa caacccgatc atgtatggat 600 accaactacg tggactggct aaagacgcac taaacagtgt gtgtgaagcc aacaatattg 660 aatggaacat cagtggaaac gttctaaacg tcacagacgt taacggccca acaacgaaga 720 gtgttcaaat ggctcctctc gtaaacagag agaccggcct gattgatatc ccattctacg 780 ccagtgccag cggaacagca cagaagaaag accagcggag acggaggggc gttcaattca 840 aatgccttct caaccctgag ctaactcccg gggttcttgt ccgggtagag tcggacagat 900 tgtcaggcac tttcagaatc aacaacgtcc gaatctcggg cggatacaga gacaacgaat 960 ggtacactga atgctggtgt tccgatctta accaagagga tattgaccaa tgaggagaac 1020 aggcctacaa gagcttctga acctgcactc gtccacagag ggttcgaagc agtacactgc 1080 cataccttgt gtggtattgc gcgttctgga cgattttaga cgcctatctg tcgatgttag 1140 accagtggtc aacgacctgt acaaagacgg cacatcggaa gagcaaccag agattctatc 1200 tgtccctgtc attatgccgg gaacagctaa cacacttatc agcttcccat tgaatgttgg 1260 ggatacggtg ttgtgtgtat tctctcaaag aactatggac gtgtttaaag gttccgccac 1320 cggacagcca cacactccaa acgatcttcg taagttcaac atggcagacg ccattgccat 1380 tcccgggctg ttcaccttcc ctaggtcgat gaacgaccct gcaagacata gttggccaca 1440 tgataccaaa gaccttacta ttgcccacaa cctgatgacg ggacaagagg cggaagttag 1500 gatcaaagcc aatggagata ttctaatcaa cagccgcaag actataagca ttaatgctca 1560 aaatgtcaac gtcaagtgtg cttcactcac tgtcgatgca gcccatacaa catggaacgg 1620 gaacattgca catacaggta actacgtgca gactggtgga acttctacat tcaacggtat 1680 tccattccat acccacaaac acggtggtgt tatgccgggc ggtggtgtta ctgctgtccc 1740 acaagcttaa aggagatcat atggacttgt ttgtcaaccc cgacacacat gacttggttt 1800 ttataaatgg tgaagctcca gtcactcaac gaatggttga tattgtcgct cagcgactaa 1860 agatcaaact gtacacattc ttaggtgagt ggttcttgga tgatcggatc ggcatcccct 1920 acttcgagag gattcttggt aaatctagga gccttcccgc tgttgacgcg atattccaat 1980 ctgagattat gagagacccc ggcgtccttg agattacatc ttggcagtca gggatcgacc 2040 ctcacacccg tgaatactcc atggagttca cagtcagaac cacagataat acagaatccc 2100 ttcccatcac tttcagaatg ataggagttt aatatggctg gaattacagc agaaggtcta 2160 acgattaaag acttggacca aatcctgaca gactacagaa acgtagcctc tcaggtcttc 2220 gccgacctag tttcaactgg agacgaagtt gacacgtctg gtaactctgc tctaggccgt 2280 ctgatcggcg tagttgctcc atcggacgaa gctatctggg aagttatcca gatggtgtat 2340 aactccttca acccggcagc cgcaactggc gtggctctgg ataacctagt atccttctcg 2400 gcaattagcc ggcatgctgc acgtccgacc cgggctcagg ttgttctaga gggcaacatc 2460 gacaccgtta ttaactcgcc tcccgcgaag atgatttcca gcagtacagg ccgagtgttc 2520 cacctactac aaggcgtgat cctcactcct aaagcttgct ctggtgttgg aatcttccct 2580 cagacagtag gcaacgacct gacgtacgag cttaagatgt acgttgatga cattaacaca 2640 acgtctatca agtacacaag tcctgccact ggcacagtaa catccgagtc catcctagca 2700 ggactggccg ccgacgtagc tacaaatcac ggaaatacct tgacaagcta cgaacagaat 2760 ggtatacttt tcatagtacc tattgaccca tttaacacca agactttcga agaagcctcc 2820 aacctgagta ttcagaaggt tagaaagctt ggtatcgctg ttgacgacgt tattggccct 2880 gtgcctcagc aagctctagc tatcgatacg atctccattc ctattgccgg atgggacagc 2940 gttatcaacc ctgttccagc tatcactggc cgtctgcgtg agaccgacga tgagcttcgc 3000 gagagattcc gaaactctaa attcgtacaa gccaccaaca ttctggagtc cctaatcgac 3060 gggctgatga acgtagaagg agtcgaggat gttaggatta tcgaaaacga tacagacaac 3120 ccagacccag ttcatggagt cccgggtcac tcgttccttc caatcgttct tggcggtatt 3180 cctacagagg ttgcacagtc tatttggctg aacaagccat tcgggattgg ctctgttgga 3240 gatacagagg ttcaggtggt agacagtctg ggatataccc atagagtcaa ctaccagcgc 3300 cctgtcgagg ttccaatcga gatcaagatc agtgtaacaa acacaggatc gatgccagag 3360 aacattgaag atatcctacg gccaaggatt gtagcgtacg ggaccgagaa ttacaagatc 3420 ggagacgatg taatttattc tcgattctat gctccaatca tggaaatccc gggcttccaa 3480 gtgaacagcc tgacgattgc caagaaagga caaactcaag gcatggcgaa cattgaaatc 3540 gggttcaaag aagtggctac attcgccgca gcagatatca ccgtaactac ggtgtaatga 3600 tagaaggaga attccatggc tgtcaaccaa tttgacagag aagattatct ggaggtggcc 3660 cgggaacggg tcactgaaca gtttaaagag aagccgatct ttgatcgctt cctgcaagtg 3720 ctattgtctg gtaagtttga tatccagaat gcactggaag acctccagac tctccggtct 3780 ctggacacag ccaccgggaa gcaactggac attatcggag acattgtagg gcgaccacgc 3840 ggtctagtgt accaagatat tttcaactat tttggattcg ctggaacgga gcgtgcaggt 3900 tattttggat tcgctggaac ggagcgtgca ggttctttcg gaagcctgtc ggaccctacg 3960 gtcggtgctc catggtactc ggtcggtgct ccatggtact cggtcggtgc tccatggtac 4020 tcggtcggtg ctccaactgg taacgccaga gagccgagcg atgaagagta tcggatgatc 4080 ctgaaagcaa agatcatcaa gaacagaaca aactcaaccc cagagcaagt tatcgaagct 4140 tataaatttg tattcggggt tcctgaagta ttcctagagg agtacgctcc cgctgctgtc 4200 cgtgtcggca tcggtaagat tctaacgaac gtagagcgta gtcttctatt cgacctaggt 4260 ggtgcaggtg cattgcttcc taagactatc ggggttaact acacatacac tgagttccaa 4320 gctggccggg tatttgctac agaaggcttc cccggaggac aaggcgttgg agacctaaat 4380 gatcccactg ttggtggaat tctgaccaac ctagtgacat aaggagttat aaatggctga 4440 ttacagtcaa ctacctattg aaaatatttg gtccacaggc ggggatatgg tagccccgac 4500 ccctgcgcag cagcaaggcg gatggggtat tcagtcggtt cctcgccaat ggtggaactg 4560 gaagtggaac cttcacgata ctaacctagc gtatttgcta cagaagggca tcccagagtg 4620 gactagtaca caagagtaca ttgctaacaa atcgttctgc actagaggtg gatttgttta 4680 caaggctgtt cgtacgcata caggaagcga ccctgcacaa gttagtgcca actgggttcg 4740 agcttttgca gattacacca cagctagttc agcactaggg ggcctgactc caagggaagg 4800 aggtattcct ttcttcatta gcgctacagg agctagcgtg tttgactcta cggcctatgg 4860 tcgcggaatg ttgaatgtag ctaatgcctc cgcagctaga agctacattt cggctcaaga 4920 aagctctgtt gtactgtcca acctgtccac tgtgactagg gctgccaaca cggttccgta 4980 cttcaatacg gatacctcca tggctacctt caacatcaca gcgttcggaa gaggacttgt 5040 caacgcggct aatgctgaaa acgcaagaaa tttcctagga ctagctaact ctgctatcat 5100 tacggcagac ccagctaaca gggcacatac tctggtctat agagatgctg ctggcaactt 5160 caacgctggc gtaatcactg ctaccctgtc tggaaacgca actacagcta acaagcttag 5220 aaccccagtt acaatcaacg gtgtggcgtt tgacggaagc caaaacattg ttcttccggg 5280 cctagataca agttatgcgg gaacggttgc acgtcttcac atcaatggag cgaacctttc 5340 gagtgcagat aagactactc agctagcact gaggaacaaa tctgacaacg actggattag 5400 ccttgctgta gtggatgaca acattctcca gtttgtattc agaagcgcta caaacccagt 5460 tgtacagatt ggcaacgaag ttatccttca cacaggaaac cagttctctc tgggcccgac 5520 tcttacagac gctaggtctc gtctgggtct cgacagactc actcaaggta gctctgatac 5580 tcaagtcttc cccagcacct tgaacaatgg cccctacttg accgtacaac ctacggctat 5640 cggaggattc aacggtagca ctaacggatg gctgttccga ttcgacgcta atggtaacat 5700 gactcatggt acagttcctg ccgctagaat cactggtctg tccaactcgg ctcagattcc 5760 agccacaact acggcgcagg ctaactctct tgttcagaga gacgcagacg gaggattcag 5820 cgctatttcg attaatgcgt atggcactat cgtcgggtac ggctctaaca tcttcagtag 5880 agcatcgggc actggcaacg cccacatcgg gttccagaga gcgaacggaa cagaactcgg 5940 tcttatctgg ggagcccaat ctaacaactc gatgaacttc cgagttgctg gcggagccac 6000 cgcagtgtcg attaccggtc tggacatgac tgttactgga agagtcaatg ctaccacact 6060 aaacgcctct ggaaacgtga atgcgacagg caacgttaac gccgggagcg ctacgctcaa 6120 tacagcaggg aatatcacag gagccgctta cggagcctat ggttctctga ccaactgggt 6180 tgattcggta tatgccaaga agggagaaat tcctaacgat atcgcaagag ccggagccgc 6240 ttgggacgct gtaggtcagt atattctggc gggagatcaa tctggaggct ctggcggccc 6300 gggtacaatt agagccggga accagttgag accttactct acgatcagct atacagccgg 6360 tagcctgccc gctggctctt acagatgcat gggcgcgttc gctgctgccg gaaaccagat 6420 cactctctgg cagcgcattt cttaatagag ggctacggcc ctctttttag aggagattat 6480 agtggaattt agaaatgttg taaagtataa aatgggttac gagtgcgaag tgaatcaccc 6540 tgattttgga tggattccat acttcgcgtg tgactacgat gacactgcga aagtcgttta 6600 cgactctatt gttaaagcta tcgacgatgg cgtaattcca gagccagaag acgtatcgga 6660 cagggatttg gaattcgaag caagggtttg gagaaacaat gaactaactc ttgcagatcg 6720 tcaagtagag attgctatcg acgatgaaga cgaagtaaga gagaaggctt ggcgtaagta 6780 tcgttctgca ctacgtaaat ggccagagca caagaacttc ccatccgaaa agagcaaacc 6840 taaagctcct aaagaataag gcgaggtaat atatgccaaa cattatgaag cctacgggta 6900 ttaacgctat ctggtctgaa aacggccaga aggttgaccc gggtgctgta aaagttgggc 6960 ttggatgggt gacagaacta cctccctacc aaactgccaa cttcattgaa tacaagcaag 7020 acttgttcaa cgcgcacgtt aaccagcacg gtattcccga atgggatagc gtcacagagt 7080 atcagggtaa cctgagctac actcaaggcg ctaacgggat catttataag tgccttagaa 7140 cccattccga caagattcca actgaccctc tgaacattac agccggatat tggcgggtgg 7200 cgttcgagga tgcaggggag gcggccaagg ttcaagctaa ccttgatcgg cacgtgacaa 7260 actacaacac cctctctggg attggtaacg tagttattgc aagacagaac ctgagtgtgt 7320 atagtaaggc cgaaggcgat gcacgttatg ccatgcggca cggcaacggg tctaacgtct 7380 tcagcgtcgc tcccgcaaca cagccaactc acgcgatccc gctgagccag ctatcgactc 7440 tcgttcctcc tgcgaccgag actgtagccg gggttatggc agttgctacg actatcgaga 7500 cagaagctgg agccaatgat accaaggctg tgagtccgct caaggccgca caggtgtatc 7560 tgaagaagaa agacaacctt tccggtctgt ctaacgtcac tgccgcaaga gctaatctag 7620 gactgtcgga tacagcgact atgccttctt ctacattcct gaaggcaggt agcaatctgg 7680 cagatgtgcc taacaaggcg ctggcaagat cgaatcttgg aattacaagt agtgctaccc 7740 agccggaaac ctatttcttg aggagcgctc agaacctagc agatgtacct aacaaggcac 7800 aagctagagt caacctaggc ctcactggga tggctacaac agaccctgcg gcggttatga 7860 tgaaggcaga caaccttgct ggattggcta acactgctac cgctcggtcc aacctagggc 7920 taggcacagc ttctactaga aatacaggag acttcctgtc gtctggggct aacctgtccg 7980 acctcacgaa cgtccaagca gctagaaaca acctagggtt gaagggagcg gctacgctcg 8040 atgtatgggg tcttcctgcg aatacaactg ctatggactt ccagtccagt cagtcggata 8100 tttccagagg atgggctcga ctaccaaacg gccttctgct acaatgggga actggtcccg 8160 gtctgtctga tgacacaagg acgaatatcc aactccctgt tccagcacga atcttgaacg 8220 ttcaagtgac cgtaatgggg acgtttaaca actccatcgg cccgggcgct ttcatgacgg 8280 atatgtggag caacaccggg tttagagtta gctgcaactg gggcaactgg tcttacccgt 8340 tcaactggtt tgctatcact tccaccctgt aattcaggag tatcaaaaat ggctctaact 8400 gagcaagact tccaatcggc tgccgatgat ctcggagtcg atgttgccag tgtaaaggcc 8460 gtcactaaag tagagagtcg tgggagcggc tttctacttt ctggcgtccc taagattcta 8520 ttcgaaaggc actggatgtt caagcttctc aaaaggaagc taggtcgtga ccctgaaata 8580 aacgacgttt gcaaccctaa agctggagga tacctcggcg gacaagcgga gcacgaacgt 8640 ctagataaag cagtcaagat ggatagagac tgcgcacttc aaagtgcctc ttggggccta 8700 ttccagatta tgggattcca ttgggaggca ctaggttatg cgagtgttca ggcatttgtc 8760 aatgcccagt acgctagcga gggatcgcaa ctaaacactt ttgtgcgctt catcaagacc 8820 aacccggcaa ttcacaaagc tttaaagtct aaggactggg cagaattcgc aagaaggtat 8880 aacgggccgg attacaagaa aaacaactac gatgttaagc tagcagaagc ctacaaatcc 8940 ttcaagtaaa tctaggaagg ttcctaatga agaagctatt gaaaagctgg aagttctggg 9000 ctgctgtagg ctctgcaact tttatggctc tggaggccat ggttcatctt tgggagccta 9060 tccttcctcc cggcgtattc gccgcagtgg ccacactggt agctgtcggt gtaagaattt 9120 cggcagtgtt tgtaactgct ggtaaagtgg aggaagcgat ttcggaaacc atagaagatg 9180 gctcaataga aaatgatact aactaaactc aaaaactacg ccctcgtagt agctgccgca 9240 atggcagcag ggtttggata tctgtcgttc tctttgtacg gcgacttagc tgttgcgaag 9300 aatgatatcc aatctcttca agctgcgtct cgacagatgg aagagcagtt ccagaaagag 9360 cgagcagggt gtgagatcac cactgggaga ctagaggcgc atatagccca aatgaagaac 9420 cgacaggagc ttctgcaagg ccacctgtgt gagcttgagt ctctacccaa cccaacccca 9480 agggagaccc aagaaaatgc cacagagacg atctctgagc cttctactgg ggatagtctg 9540 gaccctgctc ttacaagctt gctcgacagg gccttctgtt ccgcagtacc aaacgatcct 9600 tattgtgccc ccggcaagcc tgaccgagga ggttaaggta taccgagtgg agcaagatac 9660 agtcaagggg ctcgctagag cttacattct aaatactaac agtgctgcca tgtgcaatag 9720 tcaactacag acaataaagc tatgggcaga agagcagagg gctctatatg gaaagtaaag 9780 acggcaaaga aggcctaatc aaggtagcta cacagggagt tatctctctg ctaattgcta 9840 tcctaatggc ttggtctgga ttcctaagtt ccagtctttc taagcaggaa gaacgtatct 9900 ttgcgatgca aagagatatg gtatccgagg caaaacttaa cgcactagag tcgagattca 9960 atagccgact tgaaagtgaa attagtaacg taagaagaga acaacaagaa accaaccggt 10020 atttgatttt gattatgaat gccgtcaagg gtagggatac agaaactcaa taactataac 10080 ccgttaaccc acactgggag acaatataat gacaaggaaa caagactggc cgctagtttc 10140 agcagtcggg gctttgttta tctccctcct tgtctgtatg gctattctgg ctttcacagc 10200 gatgactccc gaggctcggt ttgactctgt acgccagacc tacgagattc gaattagcga 10260 atctgagcgg cggtatgaac tcaaactgaa cagactacag gatcagataa actcggcctc 10320 gtacacacag gatcggcaat cccgtttgca atatgaagaa ctcgactcgc ttaaaaggaa 10380 gattagcgaa cttgagcgga gaataaaaga aaaacaagaa taattaagcc ccgggagcga 10440 aagctcaccg gggctctttg ttattgatta gtaactctcc atactccgtc aaacagttcg 10500 tcaattttcg agacgatctt ggctaccttc ttcttacgga gtttattagc ctctggatcg 10560 gaattaatga gactcacgtc gatagcgttt ccccagtcca gttctccgtt ttcaaacaga 10620 actttaatgt tcagattctt agcttctttg tcaatacctg cgacaactcc agtacctaag 10680 acgttatgtt tctcgaatgt aggccttgga gtgtccaagt tcaggtaatt caccataaca 10740 acctgacctt tcttaacgtc ctctagctcc atttaacacc tccttagtct aatctcatta 10800 gtgtattgaa ctgatgcctc aaagacttga aagcctgcgg cccgtcgtct tctgctcctt 10860 catgaatatg atgagcgatt aagtgtatca atcctcggtc tcctagtaac aaagaactag 10920 gaatttcttt tatccaagcc acaaagcaac agaagtgtag aacctccggc atggaagcct 10980 tgaagctgga atcatccagc ttcgataggc gttcatacgt agctttaaga tcggggtagc 11040 ttaactgata tgtagcatct tcgtcaatat gctggtcccc tctaactaca tactgcaagc 11100 tcatattaca ccttctttcc gccttctgca agacgtgcct ctcgcttatg gtccgcacgg 11160 gtcatattgt actcgatctt ctcgatgatc gcacctgcaa catctagacc tcgaacatta 11220 gcatagtcca tgatacgaat gatagcgtcg gccagttcca cctcttccat cttccgctct 11280 ggcaagtgat cgtccatcaa atccttacgg actccttcag ccgcttcggc gatttcagtg 11340 gtaacgagca tcagcatgtg cagggcatcg cgtttaatcg gctcgcccgt gaccagatcg 11400 gtgttccact tgcgattaac aacctccaga ccagtcatca ttttgttaaa accgctaaca 11460 aactcgaaga cggactctcg ttcgaatagc tcaccgaacg ttggctcttg atcttcaaca 11520 gttgcagtat ggaatggcca ttccatccaa gtgtcgtgga attttctgat aagctcctgt 11580 tcatcaatgt atgagaagaa gtccctctct ccatcaatcg cattaacaac ttcagctcca 11640 ccttcccaat cgcgcttatc aataagactc ggatcgattc tcagggaagt gttgcccact 11700 tctccccatg gtcgccagcc tacatgaccg gaaccaaagt ataataggag tggcagattg 11760 tcctgagcgg atagttcctg agtctccatg gctacaacaa acgctggtac tttttctcca 11820 cttacgccat tggccaagac gaaagaaccc aagtgggtgg tctctcggct agctgggcga 11880 tgagcttcct cgatatgatc tttaactcta ctcattaact tcaccctcct cgcagaacat 11940 ttcaaaataa caatcgacac aagttagcat gccgtcgtcg cttacaacct cctcgggagg 12000 gaagttgttc ccgcaacatt cgcacacaac tcgatcaacc tccccgcatc cccagtaagc 12060 catatttact cctccttcag aagatactca ttgctaataa ctttgaagct gaagtctcgg 12120 ctcatgcttt tgaataccaa accttctcgg tacttaccgt tcaatgcaga ctcaccgctg 12180 gccattttaa ttacaagctg catgtcctct ggaacgccta cgtcccacat gtacactggc 12240 acatgtttga ccgtctcacc acctaactgg ttcagggtat tcagaatggc aagacgctcc 12300 gctggaagac agtaacgact gtccgaaatg ttgtagatat cgtacacata gtattccggt 12360 ttgtcaactc cctcgaagtt gccttgaata tttggtgcaa ccagttcgcc ttgaagggca 12420 atattcagac cgaaataccg gagacgttca ccaagattaa gctcttctgc catcgcagtg 12480 aagtgattgg agtctttctt aatcacacgc ttccagcccc gacccttgaa gaagttcttg 12540 atagcagtga agaacccgat cttctcgtct tctagacgga aaccgacatt tcgagacgcc 12600 acgcctactt ctccgtcctt gtgccagata gtgagagacg aaccgtccaa tttgaatgtc 12660 acttcaaact tctcgccctt ctgatgagcc tgatcgtaag ccatctgaat attttgtacg 12720 cgagcctgat ccgtcttcgg gatgaagttg gggaacccta gcttggaagt gccagtccgg 12780 ctgcccttgt tgcctccatt gatagctgcc tgctcggaag gctttacata cttcaggatg 12840 cccattcgat cggtaacatc ttcgtctact ttcggctctg ggctgcccgc tgcatgaaca 12900 ggtacgatca ggccttgact aagctcttta cgaagcttca tggtcttgat tcgagaatac 12960 tcttttccac cttgttcgac catattacgg ccacgcagga attcaaagat agggttgtct 13020 acagggacca tggagtccac ttcaatgtag attgccagat caccggcctg atactcccct 13080 cgtttgatta cgcactgcca accaccaaca agagctagat cgaggctgtc tgcgttgggg 13140 tgagtcttca catcatcgat acgaactact cgggcaagta cgcggtcttg ggaattactc 13200 atatgttatc ctccttgttt gaaaattggt atattacttg ttaaaccagc cgaggtcaat 13260 agctcgctct aaggccagta gcagattttc agcatctaga aggtcacgga tcgcgatcca 13320 actgccgctg tctcccggta gaccatctgt gatatataca ggtatgtcgc tgtactcact 13380 ctttttaagc ccgcaggcac aggctacatt gtctccgaag acaatctcgc tgacttccct 13440 tgcctcgtct cgaatatcga tcttcacggt gttttcctcc tgttgtgttg aaagtcgttg 13500 tattctgcac agattcctct gctgtgtcaa tagccttgac aagaaaacaa tccgtggtaa 13560 agtgggtgac ctgctggaga gaaatgtcca cgtcactcac cggccagcag tatagcgtat 13620 gaagaggaaa gctgcaagcg caacctgagt cgaatctgag aacagggcag cgacgacccg 13680 aaaggggaaa gctcagagcc tataaggaac ccatgttccc cgctcaccga ctcatctgca 13740 tatatgtata tctgcatgag agcgagaggt agaccaaagg catgtctcag gcggaaaatc 13800 cgtatggcaa gcctagggac aggtctacct ccactaccga tctatctgca tacaagagct 13860 ttgtcaagct ctgcaatccg tgtagagtat tctcaaatca atcacagagg agtgtataaa 13920 tgaaacatgt tatttaccga gaagacctaa tcgacctgtt acgcgaccgt atgaagctcc 13980 aagcgctgga ggctggtggc gttgacaact gggactggta tgaggcctcg ctaatcgact 14040 gcggatactt cgatgacgat ggccgggagc tagaggtcga agctcttgca gattgcttcc 14100 caaccgtagg tgcgtaaccg tggaggagtc gaaagctacc ttcaaagacc cttaccctag 14160 gttcttcgac gcttctcgta ggtatggcga aaccaacgac tgcatggtgg tgagctttgc 14220 agtcgtatgg aacaccacct atgaaaaggc acaccagcac ctgaaagtga agtgcaagcg 14280 cggttaccgg caaggggcta ctcagaagcg cttcagctac gcagacactt ggtgccctaa 14340 gacccggatg ctctaccggg aggatgctaa ggataagact cttaggcagt ttgctgagga 14400 aaaccctgaa ggtcggttct ggatcgcggt aaagggtcac gctattgcaa taatcgacgg 14460 agtgttgtac gatcacacta atgacaaaag acgtaccatc tggcactgct ggcaagtgtg 14520 gcccggagag gcacctgaaa aaatcgagag gaagcctgat ccaatctcac ctcctgtgag 14580 aaaggccccg gactggtatg tctaaacaca aacatctgaa gtacaaagag gaggatttat 14640 ggaaattatt tcgagaggga cgctccctca agaggctttg tttacggcta agtgccacca 14700 ttgcctaagc attctccgag ctaagagatc ggaacttgag tatgtttcgt tctcattctg 14760 tcgccccggg gagactgggt attatttcgc agaatgccct gtctgtcacg aagaggtgac 14820 tgcttgggtt gcagtccctg tcacccatgt agcacctcct acgacagagt acgtagcaaa 14880 ggggcgtgaa taacatggat cagttagcgg gttttatggg cgaacctttc gtaattgcgt 14940 tcgactacga cgagacgatc agtctatacc ctttggcctt ccgagtcgtc atggatacct 15000 tcaggggctt tggaggagct ttcaatgtga tcgtagtcac tgcacgtcac cctgacaaca 15060 gcggagagct agagtggcta cgggattacg ggttcccgat ctatttcacg gcacagaagg 15120 caaagcgtcc attcatggaa aatcttggaa taaaagtctc tgtatgggtt gacgacaacc 15180 cgttcagcgt ggataatgac cttcctccgt ggacagcgga gcaatacgac gcctaccttg 15240 aggcaaagaa gcaacgagct atcaacagag ggagtaaagc atgagcgaga ttattaaggt 15300 tgaagtggga gatcgggtgg tccttaaggc ctattgcgat acatacactg gatgtgcaaa 15360 gcgatgggcg caggcgcatg gtcgtttgca tgaactgcta gctacggggt ttgtagaaga 15420 cagttgggtc cacaccgacg aactggccgg aggcttgaaa ggcaccgttg tgatgactga 15480 actgggactg aaggaagagt gctgtgcagt acgtctagac gcctacactg accacagggc 15540 tgttgtagtt gttgacgctt ctgatcttta catcgcatgt aaggcagcaa aagctcccgt 15600 aagcacccta gacgaggcct tcggttgtga ccacgactac cttatggaat ctccggctaa 15660 cgctcagcga ctgaatgagt ccgtcgagca gctacgaact ggccaagtcg tagaagtgga 15720 cgtgcctgtg agtgtaaagc aagacgaaac tccacctgtc gtagtgcatg tagtagagaa 15780 gatttacgat aggaaaggta acgtacacct cattctacag tatgaggtag caggggcgtt 15840 aatcaggacg gtggttgaac agggagaact catttacttc ttggatgaaa tgcaaggtat 15900 gtacttgacc aagattcaat tggaggtgaa caatggagtt gtatgaccag tggcgtaagt 15960 atatgagcgt cgtaatctta gaagaagaag ataatgagcg tcagtgcatg cggcttattg 16020 aggcagttgg cgaactcgat ccctatatcc aagatttcct agattctttc tctattaaaa 16080 ctgaaggagg tgtgtaaaca tgagtcagag taagcgcgat gagattgtag ttgaagcacg 16140 tgggctagag agctacttca tttcccactg gaacggctgg gatgtgctgg acactgcttg 16200 tctcggattt tatatcaaac ctgagtatgt tcttgacccg gatattcgag agcttgagcc 16260 tagcttcttg gagcttgatt tcgagcgttg ccgtttccga ttctggggaa atgaagacga 16320 aggcgtggac ggcaaactca tggagggcaa gttgcagatt atgaccaact ccttcgagta 16380 cgtcttcttc aaggaggttt gagtggctag acagacttac gagtctgcat cagatagggc 16440 ggtcgaggag gccgtccgtt ctgagcttga agggcggtgg aagtgttctc ttcataagct 16500 acctagagcc cactatatgg attgggcagc ctgccggaat ggaaaggttg tcagctttgt 16560 ggagcttaaa gctcggaaca atgaaatgca gaagtacccc gacttctttg tgtcccagat 16620 gaagtggctc catgggatcg aaatgcaaag ggtgtttgac attcccgcat tccttgtggt 16680 aaagtggacg gactatacag gatatgtcaa aatgacagcc aatggcgtca actacatgag 16740 catgggtggc aggattgacc gtggagactg gcaagaccaa gaagttatgg tccatatccc 16800 gctgaaagac ttcacacgtt tataggagga caaatgaaac gactctgcta ccgttgtctg 16860 catcttggag agcctgtcat gctccgtcat aagactggaa tctggtataa gggttgcagt 16920 aaatgtggat caggagtatt ctatggctaa gaagaacccc gtgttcaagt ttctaaacac 16980 agtcaacagg ccctcggtag agagggataa aaccaaatac aggcggaagc ctaagcataa 17040 acagaaggag cgattaaatg aagaagggtg ataaagtgag gatcaatgac gatgctgata 17100 ccatcttccg gggccgtgtt gccactatca tcgcagtaga cgaagagggt tgcgttattg 17160 acgtgggcag ctacgaagac gaaagcggag agcttatcga gtacctgcac ctgttcttcg 17220 agcgttctga gttgtccaag caggtgtagg agggtataat gaacggaccc gagtgcagat 17280 ggtgcggaga gaaaactgaa gctgagtttg tagacgttgg gcttggatgg atgcagcaag 17340 tcactggagg catgtgtcat cggtgtggag ggtacgagaa tggttactac cagaacgacg 17400 gaaggctcac cgaggtcgag tttgccacct actggagcgg tccgttcgaa gatcatgcgg 17460 atttctcacc attcaaccac atgagagaag gcgactcgcc atgagagcca cagtacgaaa 17520 ccacaatctg ctatacatct acttccacac gttctcggaa atgaatgagt ggttgacaga 17580 gaacgctgta gatcagtgga cagtcactac tctgggctcc ggctatcaag tggctgttcc 17640 tatggaccgt gcaatgcggg accaatacgc ctcggagagg ggttgacacg aacacaaggt 17700 gatgctaaac tccgtggttg tctgaagtaa ggaggtttta tgtccaaaat gaccgtggcc 17760 caaattgcgg ctatgcacgg tatcgatctg tattctgacc acaagactgc ttgtccccaa 17820 tgccggaaga aaggcgctga caacagcgga gacaacctaa aggtctatgg tactgatcgt 17880 aataccgggg aacacaaagg tgcctattgt tgggcgtgtg ggtacacctt gctctctgaa 17940 gagcaggaaa gagacgcccg gggagaagac gaagaggagt ggaatttcgt gggaactgaa 18000 tttaacgcag agatcaacgc tcaaattaaa gagcaatgct cgtatgatcc gcgtggttat 18060 cgtggcctgt ccaaggaaac ttgccagtat ttcggagtgc tacatggttt cgacccggag 18120 actggcgaga ttgcaactca gctatatcct actactacta attatgaact cactggctac 18180 aaacagcgga tcatgccgaa gaacttctca gagcctatcg gcgagaccgg gaaggattgc 18240 gagctttttg gtcagttcag gttcaagaat agcaacagca agaaggtgct tattgtaggc 18300 ggtgaggttg accagctatc agcattccag atgctcaagg agtatgatga ccggcgagca 18360 ggcggtaaga gtgattatga accgactcca gtggtcagcc ctactatcgg tgagagtggg 18420 gcatggaagc agctacaggc tcagtatgag tggctagacc ggttcgagca aatcattctc 18480 tgtttcgaca gcgatgacgc aggacgagag gcagcagaca aggcagccga taagcttccg 18540 aagggcaagg tgttcatgat ggaaatgaac cgtaaagacc ctaacgagta tttgaaagct 18600 gggcgtcaat cggagtttgt cagtgcattc tatcgagccc gtacatggac ccctagcggt 18660 attgtagggt ctgatgcact cgacgctcga atgtatgaag ctgtgcaggt tgagaagatt 18720 cctctgccac cgttcgctaa gaagctccag aaggctatgg caggaggcat cccgttgggc 18780 cggattgtga atatcggcgc tgcatcgggc atgggtaaat ctactgtagt ggatgagttc 18840 actctgtttt ggatttataa ctcgcctcat atgccgggta ctgtgactct ggaatcggac 18900 tgcggggagt acgcaatcaa gctgctgagc cgtaaggtag gtgagaaggc agacttgtac 18960 gagaccgttg aagagaaagt ggcgttcctt gatcggcacc gtgacgctcg gtacgacttg 19020 tggcacaagg aagacggaag cccacgcttc tatctgatcg atgaccgaga cggaagccta 19080 gcagccctca aggctcaaat cgaacaactg attattcagt ttgagtgccg tgttattatt 19140 ctggacccgc ttcaggatat tctggacgga ttgagcaacg aagagcagtc ggtattcatg 19200 cgctggcaaa agggtatgac caagagtcac cgagtgacgt tcatcaacat caaccacgtc 19260 cgtaagagtg gtggtggtca gaaggctaac tcggcaggtg ctgaactgta cgaagaagat 19320 ttccaagggt cttcgtccat cttcaaatct ggtgcagcta acattctgat gtggcggaac 19380 aaggacgcgg agaacgagtt cgaaaagaac ctgattaacg tgaagctctc taagtgccga 19440 tggactggcc gcactggaat gatgggcaat tggtactacg acgttgagac tcatacaatc 19500 tgggacttgg acgactatct ggaccgatac cctgacaagc gccgtgaata cgaggcttgg 19560 atggctcaga aggaagagga aggccgggac acggaatact aaggttgaca gaggggtgat 19620 gcttatgtat catccctttc gtcgtttaca ggaggaaagg aaatgcaaca acgatttgaa 19680 acaatcgagc aatacctcga atggatggga aataacaatt tcaccaacat gacttgggat 19740 atcgaggcca caggcctgtt ggatgaaacg tctatcgatt acactgccag cccctacaag 19800 attaagccta gctacaaaca ccactgcatt gtagtggagg agcacggtgg caatattctg 19860 gcattctacg atgggccgac ctacgtcttt gacgggcgag agtacactga gagactgccg 19920 aaagcgtctt ccatgctcca cactgaagaa gttgtgactc tcaaggacta cactccggta 19980 gagtatattc acctgccgct gaaagagttc aagaactatg tggccaagcg tcggatcaag 20040 cgcgtagtgg ctcacaacat gattaacttc gaccttatgt cgatgaagct tgtggaagat 20100 atggacttca ctatcggcgt agagcacagg gatggcggtc tgactacgtg gtctgctgac 20160 acttggatgg gcaagcaagt ggtattcgac gataccctcg ttatctccaa gacttgtaac 20220 cctgacctgt tcggcggtca cagtctggat aagctgtctc gtcgtgcagg tggtgacacc 20280 aagattgact tccgtaagca tttggcaccg gatgttcgat tcctcgactt cgcagccgat 20340 atgctctact actgtatcta tgacgtaaag gcgaacaccg ctgtatggca ttggttgcag 20400 gaccacgaag attaccaact gtccgaccgt gacaactaca tcaagaattg gctgtccccg 20460 attcagttgg agaagaaggt tgcagagatc atcacctatc aggagcaccg agggtttgtt 20520 ctgaatgttg atctctgtga gaaggccgtg aaggacttgg atgccaagat ggaagagcgt 20580 cgtgcccggg tagaacctgt gcttcctcct cgtcctgcga ctaagaagtt catggctgat 20640 tacacaccgc ctaagcgaca gttcaagcag aacggggaga tcaccagcta cttgcagaag 20700 tttattgagc ggattggggc tcagttgaaa gagggtgacg accggacgat gatcttcgaa 20760 ggcaaggagt acaagcttcc gcttcccgct gacgtaccgc tgaagacgga aatgcctgct 20820 aagatcgggg acacaactca catcaagcaa tggcttatgg gtgagtttgg ttggattcca 20880 tcagagtgga aagagactga tctgactgtg gatcagaaga agatcaagct tccgatggaa 20940 aacatcgttg ctaagatcga tcgctggctg gatgtaacgt atagcacagc gtacaaggaa 21000 gagcggctgg acgggttcgg ggattacatg aagatcaccc ctcgtagcac ccgcgcgtat 21060 gtacgtcaga ggttgattga tcgtgcaagc aaggggagct gtaaggttct cactaaccct 21120 agcttcacaa agggccaaga gaaagaaatg tgtccagacc tcgaacgcat tgcagaacag 21180 tttccgttcg cgaaggatgt gattgagtac ctgaccttta agcaccggcg aagcgcaatc 21240 ctcggtggcg gcatggactg ggacgaaatg gaggatggag aggagccgga aaaaggttac 21300 cttgcaagca ttcgtcagga cggcaggatt cccacgcctg ctgacacttg cggggctgct 21360 actagccgga tgaagcaccg gaaggttgct aacgttcctc ggatcacctc gttgtacggg 21420 gctgagcttc gagagttgtt tggggttgga gatgggttct tccaaattgg atacgacttc 21480 gattccttgg aagcacgtaa agagtcggcc tactgcgatc agtacgatcc gacaaaggaa 21540 tattgcaaat ctcttatgat ggagaagcca tttgacgttc acacaatgat ggctaagcgt 21600 atttctgaga tcattggtcg ccaatttaac cgatctcctg cgaaaaacgt aaaatatgga 21660 ttgactaagt aacaacggtc catgtaaaac tgtgtgaatt caggggacag ccagaacggc 21720 caatcctgag ccaagctaga gtgatctaga aaggtgcaac gactatcgaa accacggcgg 21780 gagccggaag ggagtagagt agggtcaagt gacccgaagc gcacagggcg cgagagcgtc 21840 atgatatagt ctggtctgca tgggaacatg cagcggtaac ccttgagcaa ggttacgggg 21900 gaggattaac gaccctccct gaacacaacg gtacatacgg cgctcaagct ggtaaagtgg 21960 cgaaaaccat tggtgccgac ttgcaaactg gtcaactggt gtttgatgct ttctgggatg 22020 ctgcattccc attgaaagct ctgaaggacg atctgaccaa acagtgggaa gccaacggta 22080 agaagtatat tgttggagtg gacggtcgcc gggttcctac ccgttcggct cacgctatcc 22140 tgaacagctt gttccagagt ggcggtgtta tctgtgctaa acgtgctatg gtgattcatg 22200 accaactgct ggagaaagaa ggtctgaagg ttgacttttt caaagaagac tggaagaaca 22260 agccggaatt ctgccaacaa atgatcgcgt accacgacga agcgcagttg gaagtaaccg 22320 ccaagtcggt gagcttcaag atgttccctt ggtccctagt aggcggcaag ccggaagggg 22380 agaaggagcg agaggcagcc gagaaggagt tgaaagctct agctcaggct tacaaggacg 22440 aacaattggc tagcactggc aaggtgtgga gtgatatcgc acactacagc aaaggtgaag 22500 gcggggtgtt tgtagcttac tgccgcgctg gagaacttgc cacgaaggcc gtgagagctg 22560 cgggagagtt ctactctact cctctggtgc ctatcgagct gaccgctggc tacatcgttg 22620 gtcgatcttg gaaggattgc cactaaaact ggcattaagc gaggaaaggg gcttgacagg 22680 cccctccgcc tcctatacaa tggccacata ttcacaacat acaaggagaa acacaatgac 22740 tctggctttc attatctatc tggtaatgac cgtattccca gccttgtcgt cggctggtag 22800 ctttgccctg atcgtcacca tcatcgcatg gattgcagga gggttcgttt acttggcatc 22860 cattggtggc cgagagaatt cggcagttaa agccacactc aaaaatcacc tacggccctt 22920 gacgttcaag ctgtttctgc ctatcattgt aatcggccat ctggtgcctt cgtctgagac 22980 ggcatggtgg atggtcggcg ggtacgctgc acagagcctc tatcaagcag acgctactca 23040 gcaggttctc agcgaatcta ctgaactgct cgaagctctg gttaagcggg ctaagaaaga 23100 aactctgaag gctgtcgaag gcagcagcga gtgatacggt aatcacagaa taggaggtat 23160 gtatgaacac ggctcgactc tacgtctacg gcaaatcgtc tatggtaggg atcactgttg 23220 acaacaaggc caatcgagag tactatacct ctaaaggctt cgaggtatcg gagacaccgt 23280 tagcgcataa gagtgttgct aacaaataca aacagaaagg aggtcaataa tatgtctagt 23340 attatcccgg gtactatcgt caagctcact caaaacggat gtgacgtcac ccttggctgg 23400 ccgaaggaag cccgatacgt aggcgcatat gccgttgcag tagatggacg cgatatcgga 23460 ctcccggaag gtgaagtccg gttctgctct cttcactggt ccatcgaccg agacgttaat 23520 gatggactcg gagactacca aacgatgctg gtggattcag gtcgctacga aattgtagca 23580 gttccgggca agaagtatta cgttaagaac gttgccaagc acagcgcaca gatcggccat 23640 tacttggttc cttcggagcc agccttgtac gtaggtttcg agccgtgctg gctgaagagc 23700 atgcacgaag gggagagccc gttctgcatg acttttaaag gacgcgttga cattggcggt 23760 gaaacctctg acaagccgca gttccagacc ctctaccctg agctggtact ggaagagttt 23820 aaagaagagg cggagggcaa ggttgaagct ccggttgacg aagagaagaa agaaaaggtt 23880 gcaaagcctg ctgtaatggg ttatgctgtt ctcgatgtag acggaatccc tcttaaattc 23940 tgtctcactc gcgaagaagc ccgagccacc aagcgctggt ggggtggcaa ggcggaaggc 24000 gtatcgattg tgaaactgat taaaggagag gaggtgcgct aattgcgcta atcctcttga 24060 agaatccggg aatgtccggt ataatcgtca gtcaagtggc tgacacactc gcccagtcta 24120 gggtatttag ataggagaaa taaaatggct ttcaaactga acgtaactgc taacactcaa 24180 tccggcaacg gcggcgtccg aaaggaagtc gattgggatg ctctgaacaa ccacgtagtt 24240 gaagctgctg gcactgcctc caaggctcgc tcgatcccgg gctacatctc gggcatcatc 24300 gacctcggtg aacaagagca gaacgatgca gaggttgtgt tcactggcac tgccgaagat 24360 gaagttcaaa tcatcaagga gttcccgaac acttacttta aggatggcat tgacaagcag 24420 actcgtaaac ctgcacgcct gaagtgctgg ccgcaacgtg atatgcaaca aatcgcaatc 24480 accgtggact tccctcagat cgaagtagac aagagcctgt acctgaccgg taacagcaac 24540 aagtctccgc tccgtgttct gtacaacggc gactttactc tgccgggtca gaagactaag 24600 attgttggcc gtccgttcac catcaaggaa gtgaagcacc cgaacggcaa atgggcattc 24660 gctaagaact ccatgctgca caaactggct gtagctactg gcgtcatcaa cgaagacgaa 24720 ctcttcacca aggaccgcgt aggcgagctt ctgggtaaag tggctcagtt ccaagttcga 24780 gtgtggatga agccgggcaa aaacgacatg aaattcctca ccgaggatat tagtctggtc 24840 ggtatggtgc ctgaaggtgt tccggttcct gaactggatg agaagtacat ctacggcgtg 24900 aacctgtatg gtgagaacga cgaagaggca gttaagcaac tgcgtgccaa cgtcatcaac 24960 accatcaagc gagccaagaa ctacgaaggt tctgatatca aggcgatgat cgaagctgtt 25020 gaagctgcac gcggtggcaa ccgctccagt ggggatagcg aggaacaagc tgaagctaaa 25080 gaggagacca aagctgctcc taaagttgag ccggttcaga ccaacgtcga tgacgacatt 25140 ccgttctaag gttacgcgga agtagaggta atagaggggc ttcggcccct cctttcaaat 25200 ttcaaaggag gtaacacatg caaatcaatc tcggtcctat ttttcttctg gctgccatca 25260 ttctgtgcgt actgaagtct gccggcgtac tcgctatctc ttggactctg gcgctcatgc 25320 ccatctggat tcctttcgta atcatgctgg ttgttcttgt aggttttggc gtggtagctg 25380 gtgtgcttta tgccattggg agccgcagta aggttaagta cagttttaaa aacaacctcc 25440 gaaagaagtg agaaccgatt atgagcaccc tagttattgt tcgagtacct gcgtacattc 25500 taaaaggccc tacagtaaac aactccttct gcggggaggt ctgggaacga gagcttttca 25560 gagacttgaa gagtgctgcg gggagtatcc tcaaaggaga gccggcttat gttactcttc 25620 ctaacaatgt aaaccctgac actcgacaga cagagtggga cattcaggtt gtacagttct 25680 aacccaaggg gagcttcggc tccctttttc attggagata aaaatgagtg aaaaggaaga 25740 ggatatcgtc ctcatcgacg gcgaccttat cgcctttaag tgtgcaagtg tcaacgagac 25800 ccgctccatc attgtcagaa acaaattgac aggagaagag gaaacttgga agaatcggac 25860 gacttggcgg gagaataaca aggacgaaga gggattcaac gaggaaaact tcgaaattga 25920 ggaccatcaa gaccccaagc acgtatctta tggtatctct gttgttaaga ccatgatcga 25980 ccgaatctgc cgccaagctg ggtgcaagca gtttaagatt ctcctgtctg gtcctgacaa 26040 cttccgcgat tccattcccc tcccgaaaga atacgagatt accaagggta aaaagacctt 26100 cactcgtggc ggcaggtaca agggtaagcg tacagggcag attaagcctc ttcagctagg 26160 tcagctaagg cagtatatga tcgaagcgta tgacaccatc atccatcccg gagaagcgga 26220 cgacttgatg gccgaaatga tgtacaagaa cggtgtaagc tactccagag gggagactac 26280 tcagcgcgtg atcggggcta ccatcgataa agacgcagac ggcactctag gatggctttg 26340 taactacgaa cgtgagcctg ttcaagtcaa gttcatttca ggcctaggat cgctctacag 26400 ggactctaag ggcaaggtga ggggagaggg gcgtaagttc ttctacttcc agcttctatt 26460 cggagaccct gttgactgct accgacctgc tgacctgtgc atcgggaagg acttcggaga 26520 agtggctgct tacaacatta taaacccttg tgagtctgat aaagagtgct ggcaagccat 26580 ctacgacacc tacaaatctt ggtatcctga acctgttacc tatacagctt gggatggcac 26640 cgagcacact aaagatgcaa tcgatatcat gcaaatgtat tgtgactgcg cccacatgca 26700 acgttgggcg gggatcgggt agactgtagg gctgttttgg ctaaacttgg agtggatttg 26760 ggaggtgcag aatgagcgta agggcgcgtc cttgggagga cttcccgggc atctgggaga 26820 cagaatcggc gttcttgaat tgggtcagag gcggcattcg ccgctatctc tggtctaaga 26880 acccagtcaa gcttgagttt gctaaatccc gaaggattag gataaccaat cccagtgaaa 26940 agagcaagct taggcaccct actgtgtggg gctatgtgtg cgagcagtgc gggaaggaga 27000 ctcctcaagc taacgttgag attgaccaca agacggggga gttctccctg aagcgagtag 27060 aggatatcca agcgttcgtg gaaggtgtgg tgtttgtccg cataggagat ttggctgtct 27120 tgtgcaaacc gtgccatgag atcaagacat acgccgagcg ctacgggctg accctagaag 27180 aggctgatat cgtgaaacag gctattgcaa tacagaagca gaaggggtat gataaggttt 27240 tcttgcagga agctggaatt aagcctgcat ctaacgcaaa gcttagaaaa gaacagatca 27300 ttgaatacct taagtctaag aaggagggtg gatgaacgag gatcgggttt acattgtagt 27360 aagagacgag gcaccagagt acatggtgcc gactctggtt gcacatagca tcctaggggc 27420 agacatggca atggttctcc tcggacagga ccgggccgtt ccatcgacgg accttccgtc 27480 ccgtccgtat atgcatgcag cggcaaaaac cgccattaag tgggtggagt ggaaacagtg 27540 gagcttccgt aagatcgttg tacgagtttc tgacaaagag tacgataaga tcaagcaaat 27600 ccctttcgta tatgaggggt atgagagaac catctgcaat ggcgaaggct cctgcctagt 27660 agtgcctcct cttagcaagg aggaaacccc gaatgttctt aaatttgcaa aactgtggag 27720 gcccatgtga gagagaagct tcttaaaatc atgcgaaagc tgccgatcag agtacgagca 27780 tctattgctc tgatttggat atccgtgttc ttctggctcc cggttgtaac agcattcgtt 27840 gcgggtgccg tggacttctt ttacactgca aaagctcagt tgaaagaggg atactctatc 27900 ctgcttgatg ttgccaaggg agcttaccag tgcattaaaa cgggagagga gttggagcta 27960 tgaccagtct agctacatat gttatccgcc acaaaaagac caaagagctt tggaccactc 28020 ctaaaggaaa gcggcaatgg accacgaaag gaggggcagc ccgagcttgg agaaacgcat 28080 atgagagtac tacactagga gcgtactatg ctaaaagaga tatggaacgg tggcctgacc 28140 tgaacattcc tttgatagta ggggccgctc ccgcacgtct ggccggctgg gaagcagcat 28200 cttttaaaaa ccaatcagct ttcgagattg ttgatattgc tgaatccctg aagcacgaaa 28260 gccagttggt gctcgatcta ctgaaagatg ttattgggtt cgaagtgcca gaccacatcg 28320 gagacggata tgtccgactc accattaaaa cgtccacata cgacgatatc atcaaactac 28380 tgaaggaggc aaaatgagca tgactgaccc ccgagcgtat ttcatcaaac aggagctgga 28440 ggaagcaacg aagcttctag aaagagccct caaccttcta gataacgtcc attgctacga 28500 tacagatgta tacgaggaca ttgcagcatt cctctacggt caagagtgtg aggaggaata 28560 aggtgcagcg cgatattagt aaaactatag cagaacttcg ggacttgatc gaagctgtct 28620 ctatgctcga cgaggccttg gttatgatgc agaaaaacgg actatatgat acggacttgt 28680 acaaacgtat cgatgcattt ttgtattatc aaccgggcga gggcgagtgg gaggaagtag 28740 aatgagcagc aagaaacact ttgtaatctc tgatacacaa tgcaagccgg gtatcagtct 28800 ggattacatg gaagccatcg gtaaatatat cgtggcaaaa cgtcccgatg ttgtgattca 28860 catcggggac cactttgacc tagctagcct gtcatcctac gataagggta agcgctcctc 28920 tgagggccgt agatacgccg aagacgttca agtcggacgt gagggtctgg accgactgtt 28980 caagcctctg tgggagctac aggaacgtca acgggctaat cggaagaaag tgtaccaacc 29040 tcggttgatc tttacactgg gtaaccacga agagcgagca gaccgggctg ctaatgacaa 29100 ccctgagttg tatggcaccg taggcagcga tgagcttggt attcaggact acggttttga 29160 ggttgtcccg ttcctcaagc ctatcgaggt agacggaatt tactacgtcc actacctaca 29220 aaaccacttc actggtaagc ctctgggtgg tacagcgaac aacatgctca aggcggctgg 29280 tcattcgttt gtcatgggcc accgtcagct tctggactgg gctatccatc ctacaatcga 29340 cggaaaacaa agacttggca ttgtgactgg agcgtgctat cctcacgatg aagcctacaa 29400 aggctatcag ggcaacaacc acttccgtgg ctgtgttatg attcacgaag tgaaggatgg 29460 ttttggtcta cctatgccgg taagtctgga cttcatgatg gagaaaggag gtttcaaatg 29520 acggtttata aattctggtg cgaatgggat atcggtatta atgaatgcct gtggcgagac 29580 tactaccaga tggaagagga tgtagctaaa gccttgtcag actgcgggat tgaggatact 29640 attgaggaac tagagggtgc aggcctgctt ggcttcgact ctgttaaagt gattggttaa 29700 taggagggca tatggctgag tttttccttg gagcggccct tgcaggcttg ttctttatgt 29760 ttagtatcac tgcgagcttt accgccgaag atattgagaa agtgacttca acatgcgaga 29820 ataacgaagg cgtcaagtat ttcggagttg acttcttcgg agacggtgct gtacactgca 29880 acagcggcgc tattttcaaa atcgaccgca aatctaaata atcgaaaagg agatataaaa 29940 tgactgattt caacatcacc cctgagcaaa tggaagaagc aatggcaggt atgaacccgg 30000 agcagcgggc tctggtagag aaagccttga ccgaccgtaa atctctggaa gattccatcg 30060 tgaccgagga cggtgaactg gactatggca tgcttgcacg acacatccgc accagcttgg 30120 gtgatctgcc tctggtaatg ggcggccctg acttcctgaa gctgatgatc ttggttgctg 30180 cgatgccgga gaccaaagac gatctcctga ctctgcacat gaacctgtcc ttcattctgg 30240 actgcattcg tgaatcgatt agcgacgagg agtaacaagt ggaagagatt gtaaaagacg 30300 aggctgccct ctctggagac gatctcatgg ttgactcggc agggcttgat gccctgctgg 30360 cgttcctaga gagtcagttt aaaggtccga agggtgtact gaagggatat gtcactatga 30420 gagtgatgtg cgctaagatc gagagtcttg acgggtttca agagttgaaa gatatggagg 30480 tgaactttga gtaacgatat catcgacgtt catgctgggc aaccgatttc tctggtgcaa 30540 cggtcaaaga atcctatcaa tattcaatat tgggacgccg ataccatccc ttacggcaca 30600 gtcttggttg ttaccgagaa aaggggtgat atacgaaagg gagaattggt cgtaaggctg 30660 gctagtagtg cagatgatga gcactctgtt agggtatgta gattctctga tttcttcctc 30720 ctaatggaga ggggttatga cgcagccagt ctcggcgacg ttaaacaagc gtatgatgtt 30780 ctgttcgaag atcacccagt gactaccttt gttaactggg atcgggctca gcctttgaca 30840 aacagtgagc gctactacgg agactttctg attggcggcg accctaaagg gatgccacta 30900 ttcaacatgg ctgttcttaa aaatgttctg tcgccttaca ctgccgacga tgaggaactt 30960 tcagctatga ccgggaatcc cgagacagta gagcacaaag aagttgacga actaagtgag 31020 agggacgagg ctttagccga ggtcgacaga ctcaatgaag agcttgttgc actgggtaag 31080 aaggttgtgt tcgccaacct agaagattac ctaggcaaag aaaactatgc cacattggaa 31140 gctatggcta accacaagga ggctgtaggt agcggaggct cctctagtta ctacactgtc 31200 aaggtgaaca accccactac gaaggctaac atgccgtatt ttgcagagtg taatgacatt 31260 atcgaggcgt tggatatgcg attcggtcaa ggcaacatgt tcaaagcgtt gtggcgggct 31320 gcggcagcac agaacctagg caagctgaag gccggtaacg atgttatccg ggactacgag 31380 aaagtcatct tcttcgctca gttggagatc gataagattc tcagagaaag gggttgacat 31440 tctccccgag gcttgcgata ataggctcca agttgaaacg aaggaggtgt gtagatatga 31500 tccagaaagt aaaacagaag ctcatgatgg tgcatcctat cctcgctagc gagatcgtct 31560 ggtgcctcac cttcgcaatg cttcagtaaa acaagggagc ttcggctccc tttattgtat 31620 caaagattta ataaggagag tttatgcaaa tttctgcaaa agtgattcaa cacagttccc 31680 ggatcggcct aggtacgaag aatcacagat tcatcactac attcgaactg gagtatcctc 31740 ggtttattca cagtgaactt atgactcacc gactttttag tcgaaatgct gcaagtagtc 31800 gtgccattcc cgttgcccat atgatccgac aggtggaaga gaatcctgcg atgcctgttc 31860 actggggaat gaatcaaccg ggtatgcaag ctgagttcga actgagtgag tgtttgcagc 31920 gtagctctca gtacctgtgg aagaaggctg caaagagtgc ggctcggatc gctagcgcac 31980 taaataaaat gggactccac aagcaggtgg ttaaccgtct ccttgagccg ttccagatga 32040 tgaagaccgt tgttacagcc acggaactag ataacttctt ctacctgcgt tgccataaag 32100 acgcacaacc ggagatcaag gttctcgctg agaaaatgta tgaggctctt attaaagcgg 32160 gcccggcaga ggctctatat gatggagagt ggcatgttcc ctatgtgact cggttccgca 32220 taggggatgg taagctgcgt tacgcagatt gcaacgggca agaactcagc gtagaggatg 32280 ctatcaaggt gtctgctagc tgctgtgctc aggttagcta taggaagaac gacgagactc 32340 tggagaaagc tcttgtaatc tacaaccgat tggtagatac taagcccgtt cacgctagcc 32400 cgttcgaaca ccaagcaacg ccgatgctgg agcctcactt ctggtgtggg gattgtcaac 32460 aacagccgga ttgggaggat ggcgtaactc atgcggatcg tgagggtaat ttctggtctg 32520 gtaacttcaa aggtttcatc caacatcgtc aactaattaa agggcatgta tgtaatgaat 32580 actacggcca agaagaggaa ggagtttaaa atggcagaat ataacctgag tctggaagac 32640 ctcatgctgg tcgatggctt caaagaggcg ttccagagta ataatgagaa ggtggttagg 32700 gagcatctgt ggactaacgg catggatgtt aaaaactact cgtatgaaat ggttttctgt 32760 caacatcgca ccctgattgg ccgagtcgta gagggtctac gattctctgg ctttgagcgt 32820 acagacaagg agtggctgag cctcggttgc gcctctctgg aagctcatat tgcagcgtgt 32880 gatgatagta atctacggtt cactcttcgt aagatgcgac cagagggatc gacagaggca 32940 acgttccaca attaatgcag taggagtaga tatggaagtt acaaaggctc tcgtagatga 33000 ggccgatatt ttcaataaga tcacacaaat caggactcca acggagtcct atgcccggaa 33060 atatccggtc attgtcgaac tagcaaacca gcaactagaa gagaagttgt ggttctctag 33120 cgaaatgaag gtagagctgg ataagttgaa cctgaagttt aagttggaac ctcatcagct 33180 tcacgctgta aagactgtcc ttcaactgtt cctcaaatac gaactgatcg taggcgagga 33240 gttttggatg ggtaaagtag tccgaacgtt ccctcgccca gaggttaaac tagcggcttc 33300 gatcctgtgc atgatggaat tggcagtcca cgctgaattc tacaaccaga tcaacgtagt 33360 gctggggatg gatacagatg ccgactacgt ggcgtacaag gatgacccgg agcttatggg 33420 acgtatggag tggcttgagt ctgtgctagg cgacgaagac gatgttcttt cggtaattat 33480 cttcagccta acagagaccg cccttctgtt cagttccttc gctatcttga agagtttcca 33540 gtgcaacggg tacaacgata tccctgtgat cgcacgcggg gccaaccaga gtgctgtgga 33600 tgaagacttg cacggtgtag tttcggctga gatcatcaac caatactacg cagagattgg 33660 tcgaccattg tctgaagata ctcggcgtgt cgagaagatt cgacaagcta tcgaccatgt 33720 atatgctcat gaatgtcgta ttgtcgatat ggcgatcccg ggcggagaac ttaacggcga 33780 gtcggctgaa aactataaag cgtttgttcg ttatcgtttg aacgtatggt gccgtcgtct 33840 aggtctagaa gatcacttcg aaaacgatga cactccgatc aaggattggt tcgaaatgaa 33900 cacttatgcc tacaagatga tcgacttctt cactccgggt atgggcatgg aatacgaact 33960 agggtgggat gaagaggaat tggcaaaggc ttgggaagag gagctgaaat atgagtaaga 34020 gagatacatt caactattcc gaagctagga agaacagcca agcagcaggt gagactccac 34080 tgtggtacac tacggctggc taccagttgt tcatgaagaa atattcgaac gagggcgagt 34140 ctgttcgctc tcgttttgag actgtagcca gagctatggc tcagcacgcc cctacggtgt 34200 atcctgagtg gtgggaggag gacgaataca ctagaggcaa ggactgggaa caggtattct 34260 tcgacgttat gtgggacggt tttgtaagcc catccactcc gcttctgtcg aacggtgggc 34320 tccgcaagaa gggcactacg gtatcctgtg caggcgggtt gatggacaac aacctctatg 34380 accgttacaa tgtaatgacg gagattgcag tgctaacgaa gcatagtcac ggcacaagct 34440 tcagcctgac caactggcca tccgaaggcg atgccattcg tggcggagag tcacagggtg 34500 ttatgcctgt cattcgtgac gttatcaacg tcatggaaga ggtcgcacag ggttctcgtc 34560 gtggtagctg tgcctacagc attaaccccc gccacgggga cttctggaac gttatcgacc 34620 acctgtacaa gcgtacagaa tcgaacaacg tcggatggtt gctggacgac aattggtgca 34680 aggctatggc cgagaaagac cctgaaacgc tgaaacgatg gaagcggatg atgttcgtta 34740 agctggcaag aggcaagggc tacttcacgt tcattgacaa gatgaaccgg cacctcgcag 34800 agccgttcaa gcgagcaggt ctgaaggtag aggcatctaa tctttgccaa gaaactgtgc 34860 ttccagctaa tgacttctac acattcagtt gcgtgatcct aaactataac ctcgaactct 34920 accgttcttg gcctgagcat ctagtgttca tcgggcaggt tatgtcggat tgcaacatca 34980 gcgagtacct cgcaaccatg gacgaagtta gcattcagga ccgaagggct ctggagaaga 35040 tttaccggtt caccaaggac ttccgagcac ttggtagtgg ggttctagga ttccatactc 35100 tgctccagcg ggaacgattc ccggtcggca gtatggacgc tatgttcctg aacaacgcca 35160 tcttcaaagg gatgaaggag caagcggaag cttgtaacag ttggctagct gaggttctag 35220 gggagccaga gggctgccgt ggactaggga agcgtaatgc cactacaatg atgatgccgc 35280 caactaaatc gacggcagaa ctcatggctg gggcttctga gggcatcgga ctggacgttg 35340 ctatgtgctt caccaagcag agcgctggag gtgaattctt ccgtgtcaac aaggtgttgc 35400 tggagattat ccaagagcga ggcctcgatt gggaagagtg tgcaaggcag attaacgaac 35460 gtaaagggag tgttcagcac gtagactggc tgacagatca cgaaaaggct gtgttccgta 35520 ctgccttcga ggtgagaatg gaagactacc tgcgtctgtg ctctcagcgg cagaagtaca 35580 tcgaccaagg gcagtcgatc aacctctact tcacgtcgaa cgactcgccg gcttacattt 35640 cgtacatcca tcgtctggcc atggaagacc ctaacatcct gtcgctatac tacatctata 35700 gtatgcgggg agccggggat atctctagaa cagaagaatg tgaaatgtgc atgtaaaatc 35760 attggcccgg ggcttgacag cttccgggcc tttgtgtatt ctgagcccat caaacagacg 35820 gagggtcgaa atgaacaagt tttctgaggt ctacttctct tggagtgcag caagctctcg 35880 cgcaagctat cttatagata agggatggac tgctacgctc cggcggtcct ttgtaggatc 35940 ggagcctacg tgggtagtgg agttcacgcg atgaacaatg aactgcgaga agagtttaat 36000 cggtggtggg tccgagagga gcaggaagag cttcgcaaat cttgtgccaa aggctgggca 36060 gagtatatct ggaggtctag tcgtgaggct ctgaaggtgg agttgccgaa tcctgaatac 36120 tttggcgatt actggtctgg ggattgggcc tacaacgtag aggacaccag agacgcgctc 36180 ctacaatctg gaatcgaggt gatctaatgg aaaaatattc taaaaagcga ctgatgcaaa 36240 ctagtgagcc ttacggctcg gcaacttacg cgctggatgt agcagccggt ctacaaagaa 36300 ctagattttg tgaatttgcc tgtgtaacgg aggataatcg agtaattagc gtgtgggagt 36360 atagtgacgt cgagccagac aaacctgtgc atcccggtca gcaaagggtg ctcgtaccta 36420 actactaaaa aaaggggaaa gtataatgga acagactatt gacaaaatcc ggtatatcgt 36480 tctcgacaac gaacagcggc atgttctgac cctatgtcag ttagccgttc ataatctcct 36540 ccgtgggatt cagtggacga gagataagca tggtcagatt cacatccatg atgttacagg 36600 cgtggaactc ggtgtgcgtc aagggattat cgctgaagtg ttcctgtacc cggggtatac 36660 tatcctagag gaaactgagg aatgaacggg gcccagaaat ttcacagccc ggacggtcct 36720 gccttcaatc aaggagagct gtgggagagc tgcgaagggc atgtggtcga aattaaagga 36780 actgagcgat atggttctga aaagtgggat gttaacgttt actacgtcta cgcaggtaag 36840 tcgcctaata tgcccgctgt tctagcgagc cgacaggagc ttccagcccg cgagttttca 36900 aaagacgctt ggaacttcca agttaggtat cagcaccaag ctgacaagga gatttgatat 36960 ggatatgttc gacaagtaca tgcaagtgat gtatgaccgg gacttgaatg taaagaaggt 37020 ggaggagcta gaggcgaagc tgaggctggc actgcgatta ctcagggagt cgcgcggttt 37080 cgtcgactgc gataaccctc tcaatgtgag cggtcaaatc gagcttcttg aggaagtcga 37140 cgcattcctt ctactccctg tagccaaaac tcagcacagc gtgccagcgg gatggaagct 37200 ggtacccgag gacgccacgc tggaaatggt cgaagccttg aaggcagtgc ttgtcactac 37260 gagcaagggc ggaatcttgc gagctggcat cgcattgaac gcagcaatcg ccgccgcgcc 37320 cggtaaggag gactgaagat tatgcgacct aatgttgtgg atacactggg aatcaacatg 37380 tgctatcact gtggaggcaa gctgtatgtt cgcggagttt gcaccatcta ctgctcagac 37440 tgcgagaagg cagagaaaga taaaccgttc gtcaggatgc agcttctaca ggatatcgca 37500 gacagtaaga ggcttgacac agaataatat tctttgtaag ataagcccat cacagacaag 37560 gaggagccga gaatggccac tacagagaaa attattgagt acgtcgaggt gtgcatatat 37620 cgcttgcagg aggacgtgat ggcctattct aagggcttca gggacagagc cttgtctaat 37680 cggacaggct acattcacgg cctgattacc atggctgaaa tgaatgagca agtgagtatc 37740 gaagactgcg acaagctgcg agctagtctg cgagacgctt ctgaagcagt gatgaacaca 37800 ttggactttt aagtcaacta ggaggaagtt atgataaaag attttgtaaa actcgttggc 37860 ttgtctgccg tagcctgcct tctgcttgta tgtattatag gcatgtttgt tacagttctg 37920 cacagtgggg cagagattgt tcaatctcag atggaacaga aagacattat cgtgtctacc 37980 gatgacggca ccatcaatct cggtcgctcc gtgaagagcg agaagctgct gtacagcatg 38040 tgcatcaagg tggaagaccg taagccagct tgcgaattca ccaccaagga taaggtagta 38100 catgaagtgc ggcaggtgat gcgcccgggc gaggctactg cacgtgacat taagattgca 38160 gttaacgcag cagtgacgta tactggagag aatggtcaga aggctacctc cctgatccct 38220 ccgaaaggtg aattcctgcc ggcaggtact ccgtcagagg tgcatatcga aacgattgac 38280 cgcttgttcg acagcgtgta taatgactac aagcaaaact tcagcaagat gtgaggagga 38340 ctcatgaaag cacagcctaa agaagtagag accctatctt tcgacaagcg acccaaggcc 38400 ggggatatcg ttcgactgcg gtccgatggc aaggcttacg aagtgtgtgc tgtgtatccg 38460 acagcggtag gctgggaggc ggcgcttcga agcgtgtacg acaaaaccaa gactgtcact 38520 gtcggcatgg agtggtgaaa tgtccgcgac taacaagtgc gtcaacttcc tccctgtcac 38580 tccggacggg cgagtgatcg tccggttcgg taaaaagagg ttaggatggc tcggtaaaga 38640 gggtaaaaag tggtattatt acccttatgg atgcgaaggc aggatcaaat ccgaaggctt 38700 caaaactctg atcgatatta aggcgtggat taaaaacccc gactcggttt ggcccgggcc 38760 cctagcttga gattgactaa taagccgacg aatggtacaa tgggatgtag gaaattccct 38820 actcagtata aggaaactag caatgactag ccgctggaaa gaggccgtgt atcgcaagta 38880 ctcggtacgt cgtctgcggc aggaactcga agagttcaaa gaagctagac gctttgcacc 38940 aaatcaacgc attcgtgcat ggtttgatgc tcatatcgaa tttctagaac gccacttggc 39000 tattcgagag tccggccaag cctacccaga cgacctttgg taattaggta attaggtgtg 39060 ttgtaggtag agattcaaac atcgttagtg gcaaggacgc cacactttca gcccgcccac 39120 aaggcgggct tctttttgcc tgaaatttgt ggttgacaag gttggccgga atatgtaaac 39180 ttgcggcatc caacaaagga gggaagaaaa tgcaattcaa tatatcgaag caactatggg 39240 tagctaaaag cgagcggaag ggcgactata aagggacgct tttggcatac atgtctcaag 39300 tggacttcaa taaagatggt agcttggctg ccagcttcaa gaaaaagcag cagactggta 39360 tgagctgggc aggtaagaat gccgagactt gcttcataga caacatccct atctcggggc 39420 atttcatcgg ggacagtgtt gaacgctggg tcactgagaa caaatacttc cgtgtgacgg 39480 accctagggg ctttgttcta gaggttccta ccgggaatat ctcgaccttg ctctacaact 39540 gcacagtaat caaaggtgtg atccaagaac cttgcgtgtg ggtgcggatg ggttctcagc 39600 acgttctact gccggaaggt tcctctctct acaaagaggc tgtaagcttc gtggagcgaa 39660 aagagtcggc caagaccgtt aaagatatgg ttgcagggga tcgatgcact cttcttagct 39720 acgggacaga ggagagacta gaggctgtct accttggaca ggtgaagatc acttggcacc 39780 ttctagctaa aaaatgccgg tactctagcc gaggatgggg tgggggtcgg tggggttacc 39840 accatctaga gagggaactg gatagaaaag aattcactga gaaagattcg aagtgggtta 39900 gtgtgttcgc taagccggta ggaaagcggt ggagtatcca ttttatcctg tctccaaagg 39960 caaccggcat tcaatctgga agcgtcccgg atgaacttca gaatctcgac ctagtgaatg 40020 gtgtaaaatg ggagtacaac gagaaagacg accgtccgtc ttcctattac tctgtgccgg 40080 agagggtagt taagtgtatt agtgtagatg atcctctatg ggataatctg cacagctcct 40140 cggaggtgcg gtggacccgc gaatggaccg tggtcggagc agagtggcga aaataagcca 40200 ccattatttt agaattgccc ggcgagagcc gggctttttc atggcagggg ttattttcaa 40260 attattttta gatttctggg agtttcggcc aatatgggca atatgaaatt tctcaggaaa 40320 aggctcagaa tgctcgtata agagccgttc gagtgtgggc agggtgagct actacttagc 40380 cgtagaagga cagtgtaacg cttaatagga gggttagaat gaagattgac aacggtggcg 40440 aatatgcgta ttggctggcg gatatcaaag agtttgtttc tcagatggat gccacagaga 40500 tcgagaagag ggcttgtata gcatacttaa ttagctggta tcagcgaaga gtactgcaca 40560 gaattaaacg ggaggaatac gaggcgatct aagctaggga ccggatggat ttttagggac 40620 tggatagatt ttcacagact gcaaaattga gaactgggca gatttttagg aactggacag 40680 tttttcacag aaggggattt ttctacagag gaatttcccc tgaaatttag ccggatttct 40740 cagaagggcg gatcgttagc aggctatcta attggttagc aagctacctt taatcgttag 40800 cacactaact aaaaatttct aggacggacc tcagttggca cgaacgttgc aagcccgcac 40860 cagtttcccg ggcaggcgta ggcctcgact atccgtcgtg aaggcgatat gtagttgggg 40920 actcgcaccc cgcgtttaag atgcgcccat tctactatga caaacccctt tgtcaacata 40980 atttttatgg cacagtcttt gcaattgcaa ttagcgtgcc aatctaaatc tcaggctccc 41040 tccgtgtttg cctccggtgc tcggcttcct gcctgcgttg cccgcctgcc tgtcattata 41100 cacaagctat caagacaagc aagaaaaatt atagagaaaa atctacataa aacaggttga 41160 caggcctcct ttatatatgc acaatgatcc cacattcaac ggaacggcag gtaagcagcc 41220 atgctacata gtgaagcccg ggcgatggcc ctacaagaga tggacaagtg gagcctcctc 41280 gaacaaggtt ggaaattcag tttcaatctc aggatgaaac ggacgctagg ccgttgtaat 41340 cacgctaaaa agctcataga gctaggttac agctacgtag ctgccaatgg agtgcctgcg 41400 gtattagata ctatccgcca tgaaatagct cacgctaagg cgggaccgga tcagggccat 41460 ggattcgtat ggaaagagtg gtgcggattg attggcgcta aacctaagca gtacgccagc 41520 acaaaagaaa aagtagttaa tttcccgtgg caactggcga ttcagcacga ctccgggcgc 41580 ttagagcggc ttaaccacta cggtttcaga cggaccaaca tggcgaaaaa gcaggtacgc 41640 gggcggcctg agacaaaggg cagactagtt tgggtgaaga gtgaaaataa gggttgacag 41700 cttgggccat tcgcgtagaa tggccctcaa gcaaagggaa acaccctgag cagtcacaaa 41760 ggatacatag ttatgaaagc gctttgtaat catcgggcac tctacgcggc ttacaatcgt 41820 agcgagattg atcgcgtagc ggtagacttg aaccgctatt tccctatcga gaaagatgat 41880 gaatgggaag acggatcata catgtatcgt cgccgcacct atctggtgaa gcattcgaag 41940 ggtacagccc gttggcacag tctttactgc aatgggatcg tccaaggcgt tggcgtcatc 42000 ttcgacgtga aatcgggtga acctttccgc acagcataaa ggagattcag aaatgcaagc 42060 ttggaacgta taccagaacg gacagttgat cgatattgtt ttcttcgata ttatgtgtga 42120 taccgaggag gtgcggaaat cgctggtcaa tcacgacgga tactcgtctg atattactgt 42180 agaggaggtt gagtaatgga tagtctatct gttaaaatcg ttctgtcgga actgagctac 42240 aaggctctga ttcaagcctt cgccttgctt ggccgaacgc tcgacctaga cgaggggttg 42300 gacgatatac ttaatcttat tgcggatgag atcgctttcc gcgacggcct gccgcctttc 42360 gcagacgact gcgataaaac agaatggatg ctccgtcgat gggaatcgct cccggtggta 42420 tcgtacaata tcgggcagga cggaccgatt gtcgctcggt ctatcgaagt aaaaacggca 42480 tgaggggaga actgatgacc gtcagagtag gagatatcgt ggctatccgg ggcgacattc 42540 ggaaaaagct cgacggaacg tgccaataca ctcccgaaca attggtaggt ggtaagttcc 42600 tcaagcatgc cggcacggga gaaatatgga ctggccgagt gagtaagata caaggtgata 42660 tggccaaggt gggaggggct tggcgcggga tcgaattcta tgtgctcatt agtgaaataa 42720 acgcttgaca acctgaccca ctagctgcaa aatagcaccc acagacaacg aagacgccga 42780 taggcgagga gaaagcagat gcaaatgttt ttcaaaaccc gtacccaagc ccgtgcaatg 42840 gccaccaacg gtcgcaaagt ggtagacaac ggggctcaag ctgaaaagcg ctgggctgtc 42900 aagctgaaca aaaaggaggc gaaataatgg ctaagtctgt cagtgtagat cgcaagcgtt 42960 ccatcctcga cgaggcgaaa gacggtagct ttttcagtgt ggaattcgtc aaggcagacg 43020 gcaccgttcg aaagatgacg tgcaagcgcc agattaaatc ggcgtatgct aacggacagt 43080 atgccactcg caaaccgacc agcgctggca agccgcacct gtataccgct gctgaggtgc 43140 tgaacatgga agagggtaaa tccgctttcc gtacgatcaa tctcgaaacc cttatccgtg 43200 cgaaggtgaa cggaatcgag tataaattcg attaaaagct tgacagccta ggccattcct 43260 gtagaatggc cctcaagcaa gacaaactta aacagaaagg agattaaaat ggcacgttct 43320 atcaaggctt ccgacttcga ttccgcttac cagttcgagg ccgccaaacg ttccgaacgt 43380 aaagagtccc gcaaatcgcg tgacaatcgc aaagctagcc gaggccgagc tttcgacttc 43440 agtagcgata tgtaaggttt gtgccctgcc ggcaggctta aatgccggca atcctaagcc 43500 cattcgtcga gtggttttag gattctcaac cccagcggag ataccaaaaa tggttcgtca 43560 atgcgtaccc tgtcccgatg ctcgccatgc tttttgcctt gcatggttgt tcgccatgcc 43620 ggagttcgcc ggtctgcctg ctcaaaagga cataaaactc tttaagactt cgggacagtg 43680 ggcggtatgt tatggctaga cggcagcggc tcccgtcgtg ggttcaagac cagaccgagg 43740 atgaaacgcc gctgagggat aggatagacc cctaccttag caagcttggc gaagtcgata 43800 agctagaggg acaattgcga cgggtcaggg atgcaacgga cccggacgaa tacaacgaaa 43860 tggctaaggt actaaaagcc cgacgccgga agataatgaa gcaacgtgcc cgggcctacg 43920 gtctgccaga ggatgagcct accaatgtcc aagggtacag cgtaccggaa gaggttcacc 43980 gtagagccat cctgttaagc agtgtaaaac cttggatgtt ctggaccatc ctgtctttct 44040 cgatttttgt gtggtttgtt ttgaaaaaca gttgacaagg ttcccgcctc ctgtagaatg 44100 gtcagcaaga aaggcggaca ggccgcctag ctagacaaag gacaatcgtc atgaacttca 44160 ctctcaatct cgtttccaaa aacagcaaaa ccggtcccat gcctgttagc acgtctcata 44220 acggcacctg cccggatgcc tgccctctca aggctaaagg ctgctatgcc gcttatgggc 44280 ctactgctat tcactggaaa aagctaagca agggtgaacg tggcgtagag tggaaagagt 44340 tccttaagca agtgcggtct atctcccgtg gggatttgtg gcgtcataat caagctggcg 44400 atctcgtggg tcaggatgac gttatcgatg ggatcgccct gatggaactg gtgaaggcta 44460 acaaaggccg tcgcggcttc acctacacac attacccgat gaacaatttc atgaaccgcc 44520 agcacgtatt gtcggccaat cgtagcggct tcactatcaa cctgtcgggc aacaatgtag 44580 cgcacgccga tgaactggcc gacctgaaca tcgcccctgt agtgactatt ctcccgatgg 44640 acgcggagaa tgtaagcttt acgtcgaaag gacgtaaagt ggtagcttgt ccggctgaga 44700 aaagcgacaa ggtgaattgt aagtcgtgcg gcttgtgcca agtggccgac cgggagtata 44760 ttatcggctt ccgtgcccac ggcacagcaa agaaaactgt cgatctcatt gctaagggtt 44820 aacacaatgg acgaatctgt ttacgcacca ttcaatcagt gtaagatgat gggcctagaa 44880 cgaaccgtgc ggagcctagc ggctcctaac gggtgcaagg tagtcttgta tcaggaccat 44940 aagaacaagc atagaatcgt catatacgat gccttagggc atggaatgtc tggggtcatg 45000 gtgcaagcgg atggggaaat tcactacaag gaaacccgca aggctagcca agggcaaaac 45060 ctgacaaggc aactacaagc ccaactgacc gcatggggag tgaagtggtt tccctctcag 45120 tatcagacaa cggcaggcgc agcttgctac aaaggagacc ggtaatgcga cagcttaaca 45180 aaacccagct taaggccttg gggcctaaga tcgatctagc tctagagctg gccgcgaccg 45240 gccgaggtga tcttatgaac ggccacggct ccacctgcta cattgcaaac aaagctggac 45300 acaacatctt gcggatcagc tatcataact cccgattcgt tgcatatggg gctgagagtg 45360 tcagggtgac tgggaatgtc attgcagcat gggtagaatg gaagggcatt aaccgggctg 45420 caatcgacgc tctgagtgag tacgggtatc atcctaacct gagcataggg cacaacgatg 45480 ctcttaagac tctgcgtgat atcgagcgtt accagtgacg gccacctact cgacagaaaa 45540 acgcgggtcg cggtgggcca tcatccgtac tgagcccggt tatagaggtg accgggtgac 45600 cgtgctagga ttctgtatca atcaaacgca cgctcttaaa acggtagcca aattccgggc 45660 ttggcaagcg ctaggctggc cctacacact gaaagacgac agaaaataat gcttgacagc 45720 ctaggccatt cctgtagaat ggccctcaag caagacaaac cacccattag gaggctagaa 45780 aatgaaagct gtagctcagt tcaaaagtga agactacgca agcggtgata gccgtactgc 45840 taccgtctat gaggatgttt atggctgcta catcgtgagc gttttcggaa ctagcctcag 45900 cgagcctatt gctttccatt ggggaccgtt cgaggataaa gagtcggcgg tagacgcagc 45960 taaatcggcc atctaatccg gagattacag aatgaaaatt tccgctatcc tgaaaagtaa 46020 cctcgaactt tacggaccga tgactttcat gtgcaacttg atagaagatg atccgactct 46080 aggggaagag gaggtaatcg aggctaagcg gtttatcgag cgcctgttag gtaaagcctt 46140 tactcttcac actaagttga agagtgaact gcgggaatat gacgttgcct tcactgttaa 46200 cggcggtttc gggtctaacg agtgttttca aatgcggcgc ttgtggtggg aaactgtgat 46260 cgaacaactg gaggctcaag ggaaatgacc caatccaatt ggtgcaaagg cgtccgggtt 46320 gtcggtggaa agcgtgatgg tgagattacc ctgttcactg atgcacactt cagcgaatct 46380 ctaggctttt gcggaggaga ccccgacttt gttgaggctc taccgatgcc tgctgcactt 46440 cgcctgctgg ttaaatggaa caagctgtgc cgccaaatga agcttgacta tcggtacgaa 46500 ctgctgtagt ctgcaatctc aatcaaaaca ggaatgctct aatgtcgatt ctagccttaa 46560 ccctgaccct ctgctctgct gtccaatgcg atgattacat catcgaccac acactcccgg 46620 cccgggccgc agagtgcaat gctcggctag tggaagaggc cgatgagttc ggcgatgctt 46680 gggtggcgac taatgccgat acccgcctga cccgatacct tagccgattc aatattcagg 46740 ttgacccgcg ctttgttttc gattacgatt tcacctgtca actgatcgca gaggatgaac 46800 tgccatgatc gctccacata tcaccaacaa acaataccgt agccgtgccg ccgtcatcat 46860 ccgtcgagtg aaatactatg aaagccgctg gcttcgtact gtagagtttt tctcaggcgc 46920 ggccgctcag aacatcgcag aacgctttgc ctacgctggg catgctgaag agcaaatgtc 46980 caagctcaag gctgagtttg cagccttccc ggtggaggtg aggctagatg ctctaggttg 47040 gataaactgg aatactcata acgacggtct gctagaggag tggattcatc aggatagtga 47100 ccgtgccatc atgctagagt atgacagcga atcgaagcgg cctgtagcct gctgggaaac 47160 cactgtcggt gctcttccca agctggcaat gctgtaaaat atcgcccgtt aggctgaaat 47220 aatgcttgac gggctttttc gtacctgtag aataggcggc acgaaaggga atttctcccc 47280 gccgccatca ggagagagaa aatggcaatc ggtgatagct acgtcaaaca agcgctccag 47340 caccgcgaac aagctaagat ttgtcggaag tttggagaca ttctggaggt ctaccactgg 47400 cggaaggctg aggagtttat gagcagagcc cgtgctttga ttcaatacca tcaccagcga 47460 aagggcaacg tggctgaagc ggagcatcac gcacggaaaa tggttgttca aaaccaacgg 47520 atggtcgctc gcatgatgcg tgaagtttgg tattgaaact caactgttga cactgccggg 47580 ccctccccgt ataatgggcc cgtcttctac aaacaaccac ggagatatcc gaaatgaatc 47640 gcaccacact gcgtaacaaa gatgtagctt ccattctcca gatgggcatc gcctaccgga 47700 atgatcctaa tcttacagac gagaccattt ccgcaatgga tctaaaatat atgtgctatg 47760 tgatggatga actattccgt tgcgggctgc tcagtgctaa cgagctagag cagatggaga 47820 aattcatcgg tgacgcactt gaggcatggg attgtctcac agcggggtcg atggctgcca 47880 ccgctgccct tagccgaggc gaagagatgc tatcggttga tgcaacccta aaagatcggg 47940 acgaagtgta cgtttggtta atttgggact tgctcaaggc taaccgctag gctagactat 48000 ctcctacaac atcattcaac ggaactcaca tcatgatcct cgttcacggc actactgaga 48060 aaggcctcaa agctatcatc aaccgcgacg gaaaagatgg actagcggca ccttgggacg 48120 tatctgataa cgatcgtatg tcctacttct acgatgcggc gaaagtagac tggacagaag 48180 atttggaaga tgcgaaacga gagtgcatcg gccacgcact tgaacaggct cagttgcaaa 48240 aagctctgga ggcagagggt gggaaaatct acgccttagt cgtggacgtt ccggaagaat 48300 tcgtcgatat cgtagaagac gactactcct gtcctaatat ggagtccgtg gctagttgca 48360 tgccagagga acggtttgat cctgattgga ttgtggaagt gtacgaagcc aacgttaacg 48420 tgtggtctat tccgttcgtg ctggcttgtg ttattggtaa cccaatgttc caaacccata 48480 cactgccaaa ggaactagta gatattgctc aacaactggc atcgtctgag acctgctacg 48540 atattacggg tttggagtgg aacaaggtct ctctcagcat cctgtcgaat atcaaagaca 48600 aagaggagga gtgaacatga aactatcgga aagattctct atcgggctga aacacgcgat 48660 tcaacgcaac tgtcagtggt acatgtgtat ccgcctccgg gaagccaaag ccgattcact 48720 tgagatgggc tccataattg gaggcattat gcgggatgcg ggcatggaag ggacaagagt 48780 agacggtgct ggcgtggatg actactttgt aacgtctggc atggccgacc gttacaagat 48840 gacagcctcc gaagagtccg catacggtca gccagagtat gctatgtggg tgcaattttg 48900 gttcttcgta atctttgact tagcccgaaa agggcagtag aatagccggc agataatgtg 48960 atctaagggg cgatcatgaa agacaagact gtagtttatc gaatcgagtg caagaacggt 49020 gagggccctt atgttaacgg gtgcatgacg aattcgtctt ccactccaga gcggcctgtc 49080 cctgagcatg acgggatacc agatgttcgc tattttgagt tcttcgcctt cacgtcccct 49140 aggcagctag acgattggtt tggcgatgaa tacgatgtgc tgtccttcta ttctaccgca 49200 cggatcagag tctatgaggt agacaagcaa catgtaagag tcggcatccg gcaatgtgta 49260 ttccgcaagg cggaagctga ttgcgtccaa gaggtgagca tagaccaatg ggttagcatg 49320 gtacgcgccg gactattgtc cgcctcggtc acacaaactg tagctccacg tcctaccgag 49380 caattgtccc tagacctagg ggatgactcg gcctgtgagg cttcgaaaga aattttgaaa 49440 atcttcggtt tgtagggttg acagcttggg ccgttcgcgt agaatggccc tcaagcaaga 49500 caaaccgccg gcaggcaaaa ccacaaaccc ggagactcac catgaacaag ccaatgaaca 49560 ctttcgcata cgcccactac gtcgcccgca tggacaaggc ctctggcact agcctgccct 49620 acgccaccct gttccgcatc gccctgcgta acgcctaccg caagccgggt gtccgccagt 49680 acgattgtgc agcactcgtc gaggatatca aagcgcgtga actggtccaa aagcgcattc 49740 gggctgaaaa agcagtagtg atggcggcag taatgcgtgc aatccgtacc ggcttcaccg 49800 ttagcgtgaa ggatggcagc gatggcgagt gggtagtgaa gaagtctacc gatatcaagg 49860 aaatttctga cagcctgcaa tcgaccgacg aagatatcat ccgcttccga aagggtgacg 49920 gcccggacaa catcgtcggc tctatgtggg caatctacgg taacagcgct ggcgaagtga 49980 tcgccgactg gaccgaaaac gccaccatgg ccatgattat ggctccggct gagcggaaga 50040 tggaaaaata cgctgaatta ggtatctaat gcttgacggg gcccgaaaag ggccccataa 50100 tgcacccaca tcagcaaaca acatcaggac tgacccgatg agccagatca aaatccaaga 50160 atacatcgta gccgagatca aggttaacca ttgcgctcac ctgcgcaagg gccagaccat 50220 ccaagcccgc gatgctcgta gcagtgaaaa gtggattgca ttcatggtgg aacgcgggta 50280 tagtgcctct gaagccgcta tcctgttcaa agatgcacat gatgtggcaa ttctcgaact 50340 ggcagcctga agaaaatcct actaggggta ctgacaaatg aaacgccaat atactgattc 50400 ctaccaatgc aaagcaatca acggtctgat ttctgcctgc ggcggtaaga aagctaccat 50460 gcaagctcgg ccttccttga aagcctctag aaagaaactg atcgataaaa tggtcaagta 50520 tattgcccgg tcaggatgga aaccgtaacc aactgattat cacagccccg gcttgccggg 50580 gctcacaata ggagataaaa gcatgaatac cctgattatc cgtttggatt ccgcctacag 50640 cgttcaaact gtccgtagtt tccttacgga agctgtagag agtattcgaa agcatatccg 50700 ggactacgcg gtgcatgacg aatacgattc gggattgagc ccggtagcac ccaatcatcg 50760 acttgcaatc gtcaccttgg acgaagattg ccgagtgttt cacattcaat gcgagtcacc 50820 tgatctttat ctggcgaacc ctcggatcgt gtttactgat gttgaaagcc cggcatatac 50880 cactcccgtg aacgagatcg aagagtatag ttacatgacc gcatggcagc atatacgcca 50940 aaaagatatg acagcaaaag actacctgtc ggattggtct atccttttcg cctcaaagga 51000 gaatgccatt gatatcgacc cgcgccccaa tctgaaaacg caaatcttgc attaaccgag 51060 gagggtcatc aaatgaataa caagtataag gataacatca ttgcagaata ctgccatttc 51120 gacggcagac ggccagtcct ttccttggcg gcacgatggg tccaccacga cagtcgcgtt 51180 gtgaagctgg cagcgctctt tgcctgtgct ggctatggcc gtccttacaa agattgtatt 51240 cgtgcctaca aggacgccaa gcagcgggaa aaggatatgc gaaaccctgc caaatggaag 51300 ctgagccgag agactaagcg ggctctacgg gcccggctgg cgtccaaaaa gaaactcaaa 51360 taaactgttg acagcttggg ccattcctgt agaatggcca tcaagcaagg ggatgagccc 51420 taagcagtag aagaggtgag aacgatgcaa gcgacctacc aagccctgaa aaccctccgc 51480 gatgcttgcg aagctgccaa ggatgaaaaa ggcaccatca acggaaacaa gctgaactcg 51540 cttcgcaata aggctgtcaa ggaaatgcaa gctggtggcg aaacctactc tgatgctatc 51600 gccatggccc acgacttgat taagaaatac cgcaagtaat caatccgtaa caagccccgg 51660 gtgaccgggg cctctcatag gaaagaccat gaaaaacgtt caaatctgtt gttcgaagtg 51720 tggagccatc aacggcggta acagcaggca caattgggtt atcgcattag gcaagaagtg 51780 gtgcggtcat tgtgggtcca atctcacaac ccttcgtcgc taaccattca ctgagaccta 51840 atcgaggaga gatcatgaac gccactctgg cacgcctaca gaacgaacgc tgtgcaaccc 51900 tccgcctgat gctcctgccg gaacatcgtg ggtatcagtt ctctggccat ccttgggccg 51960 agcgaatccg caatctccac gatgaagctc ggtgcatccg cagccatcac agctaacccc 52020 attcccagcc cggcacagcc gggctttctc tcataggagg caagtgaaca atggttaact 52080 atctgatcct ctttttcgtc atagcaatgg tctattgcgt gataggcgct ttagtctctg 52140 gaatgctact aatgctaaaa gaggctagct ctgaatttga atggcctacc cgcaaagaga 52200 aagatgttat ctacgtccta ggtgcaatat ggcctatctc gttaccattt ctcgcagtag 52260 gcattgtcct aggcataccg gcgatgggaa tcgcaaaggc agtgaaacgc ctaatcaaaa 52320 acaactacta agcccactaa aaccaacaaa gctctaacag cccgccttgt gcgggctttg 52380 ttctatctgc gaaagcggag ctttcaagtc taattaacat gtaatgttgt aacactctgt 52440 agagggtaac accagcatga caagatagac cacttgtaac gttaacgtta catgtataac 52500 agcatgacag cggaagctgt atgttcacat tctgtataga taaccctatc aaataacccc 52560 acaataacct acctaaaacc taccggttta aagcggcctg ataggccgta gatgaagcga 52620 tagcttcgct atgttagtct gcaccgtcaa ggcgaaagcc ttacagcatg aggcttgtag 52680 gaggttttag aggcatatgc gattagcata ggatgttggt tgttttgagt agattttggg 52740 tataacccct ttccgcgcta ccattgtcac agtgctgtta agcgacagct tacatccgct 52800 ctcattttgc aatgagaatt gcgtacagtt catcatgcgc ctcagaagtg acttcacttt 52860 gcatgcggat gcatgctata gtataccctg tgatagctcc gctatcccgt tttgcatggc 52920 acacgaattg cataagcatg acaagggtaa ccctcgaaag cggagctttc aaagtgtggc 52980 tctacccttt agtatattgc gaccggaagt agtgacactg aaaaccttga ctccagccca 53040 gcaaatacgt taaactaaag ggttgatagc tgccgctatc gagtaaccaa cattcacaca 53100 aggaggtaca atgacaagca acaatcatgc caagattcac atccattacg ctaagcaaat 53160 ctactacgcc atgcgtaaac gtgccatcgc aagcgatgag atatgcaagg aatgggccaa 53220 gcccaagacg ggctttgaag cgttctatga ttgggtggtg aatgtgtcag ggtacgccgt 53280 aggctaccgc ctagacagga atattctctt cccgggaaac aagctctatg ctccgcatac 53340 atgcgagttc acacctacat acatgcatac tctattcacc aactgcgaca agacaagcaa 53400 taaccgtgcc aatacgtggg atagctatat ccctctaggc gtccgcctag cacgctatga 53460 caagtacggg atgcctgtat acgtggctca gtgtaggaca cttggaaagc agtctaccct 53520 tggatcgttc gacgatccga tgcaagccca tgcggcatgg caacatgcca aggtagcagc 53580 tatcctcgaa tgtattgatc tctatcagat ggaggatgtc cacagtgtga acgttgttca 53640 agcgttgctt ggaagagtag accagcttgg caaggatatt gcacagggaa aagagacaac 53700 ccttttgcaa tgatttgatg gggtcgatgg tcaacccctc ttagagtgcg ggaactccga 53760 tagcgaagct atcaaacgta tatgcatatt ccatgccaac atgtggaaag atttcacccg 53820 gcagggcggg agcccgttgg cattagtttt gcatagctta gctgtcgcta agaaggaaag 53880 accacggcca cccattattt tggatttact aagggttagg gtagcgaggt gggttcgtgg 53940 ttaagtagct cggaaataaa tccataactg gcagaaggcg aaccagcaga gggcaggcct 54000 gctccctcca ttattttccc agcagtagag gagacacact ctacaaacgt atcactctct 54060 tcggcggggg tttaggattc gaatatacct ttagcggcta aatgccatca tcgcttattt 54120 cctattttcg tgctataatc cttataggat gtgcttattc ttcattatag ctggataagc 54180 gatggttgta tagattcacc acaaatagaa ggaatataga atggaagata atattcaagc 54240 tccgcttgca gctagtgcag atggcaaatt cgcaactgta tacgaagcta ttgtcgcact 54300 cggagtagaa ggggctgccg ctgtgtacag ggtaggtgta gggaatagat tgacaacagc 54360 tagaccatcg gcgtggtaaa gagaagcccc gggcagcgaa agctgatccc ggggcttttt 54420 attgccttga gtttatgtat gaagagattc cagttgtctc tgctcttcca tatactccct 54480 agtggcgtag ttcatcatga ggttgcaata ctcttcgttt atctggtcca tgtattgcaa 54540 cactttctcc atgctctggc atggactaaa tccattatga cggagaatct tgcttagatt 54600 accctcattc cagaagtctc tggcccaagc ctccaaagct actgcgtaga ggcttttgat 54660 gcacccgata ggggatggat accaatattg ctcagacatt agaccctcca aacgcagcaa 54720 acaccccttg cttagctagg atagtcttta gctcctccag tgaaatggtc tcgtctccta 54780 cgaccacata cttgtctgcc ttccctagag tcatcacaca cttagtctgg aaggtaggcc 54840 gatacaagtc atacacatcg ggttgccact tgcttcgcag gccagttccg tagctaatga 54900 accggtcttc gggatgatcc cggatgtata ggcaccgggg actatcatct ggcccatcta 54960 cggagatagg gtgttccatc cactccctga tcttatcaac gacgccctct cctaccttca 55020 attgagcgta ctgacagtac tcaaggaacg catcaaactg ttcggcagtg aaattgctga 55080 catcgatctc tttagttttc attctcttcc tccatttctg caatgatttc cttcaacgct 55140 tgaagcgtgt aggtgccatt tagctctgta gtaggaccag tgtcacactc atgaagtgtg 55200 tacgcggtca ctttcttctc agtgacgaaa tggaagtcta cccttcggaa gtcgtaggtc 55260 gatttcgagt atccaatggc ctctttgagt tcttcctcgt accacaggaa tgtcattgga 55320 cttccgtcgc ttttacgagt gtagtccagc agattatctc caacccacag tagcacttga 55380 gccttgtcgt acatgaagcc gtttccgctc ccaaactcga taccataagc cttaaggtgc 55440 tgttgtactg caatgttctc ttcgggggtc ttcacaatag tgtaaaattt aaccaaacgc 55500 tctttcaatt gtattcctcc tctaacatga tactgctgta caggatttcg aacccttcgt 55560 ttttcaagtt gtagatatat ctcccttcaa actcctgatc gatcaatcgg agcctgctct 55620 ctccgttctc tatccatccg cagaccttgc taccctctac aggctttccc tctccccttc 55680 tcatccgtgt gcagacgtag tatacctgac gtgcagacgg tgtaaagaaa gagtggaagc 55740 tacttagctc cagagcgcac gtccacatgt ggaagcagtt ctcattagac tctaagtctc 55800 ggtagtacac ccgcataccg tccttggtat gagcgtatct ttttcgggcg taaggaggaa 55860 tatcctctaa agaccccaca atctctaagt gttgcttcag attctccaat ttattcctcc 55920 tgtctgtgtt ttatgagagt atagagtgtt ctcagtaccc tgtcaagctc tctgtgatag 55980 cgtggtttag gcgctcctct gcccgcttca gaattgtatg ccactcgtct ccctcttgga 56040 ttcctacata cttcttcatc atcagcgcac gatcaacaag ccccgctctg tagttctgtc 56100 gctcttttct acgggacagc actcttgaga tatggtcctt cttctttgcc aacacgctga 56160 tagctttcct tgccataaga gttgcatact cgctctcctc ggcggtcatc cattcctgat 56220 acagcagccc tagacgagtg tcatgctgta cgagtggaag gtctttccat atgataccta 56280 ctcgtccagt atcagagacg gctttccatt ccagcgtagt gccggtctta tagtcggtga 56340 tctttacatt ctccgagtta gattgagact ggaaagcgtg cctccagtct cggtatacag 56400 tccaccgttt ccagtcgaag aatgtctcac agatggcttt aacaggttct ccgattttac 56460 cctccagttc tttcaggcgg ttctcctgct cagcactcat gtatttgata ggtcgggagg 56520 cggggtcgta gcactcctcg acccgggcct ccagtagttt aggctcctcg ttccgctctt 56580 cctctcggaa ccatgcgaac agcttcttaa acatattcag tcctcctctc ctgtgatagc 56640 taccctagtc agtctccaca cttttctagg gagactaacg aggaatagca tagccataaa 56700 cggtacggcg ataggccaga atattccagc taacaccgct cgggcctctt tcttacgcct 56760 ctccgtactt tctcccctcc acccaagaag gggtcgtaga gattcccata cgaacatccc 56820 tatcacagag tagaacaata ggcagaccac tccgacgact atgcatacga gaatgagaag 56880 ccctacttgt tccatggtgc gatcctctta agtagtttac ggctgttcca gatagacaga 56940 gcccacttag gtaacaacac cactttcaaa acgctgtatg ttgcgtagag tagcagaaag 57000 ctagcataca ctgtgaatgt aataggccat agcagtccca gtacaatggc aaaagcctcg 57060 ataccctctc tgtgatcttt agtcgcacta gctgggaagt tatctttgaa atactccgtg 57120 atacccatgt aggtccacat gaacgcaatt ccccacgcga gcgcgaggac gaatagcatt 57180 gggattatct ccattactca cctcctttga gagccccact agggctctaa atttttggtt 57240 cgacctgcgg tcagcacatc acaacccagt tgtacaggtc agcctcctcg taagccgatg 57300 ggtagcgatt gtactccaag aagaacgcat ggtcaatagc tgcgtatttg gttgcgaagc 57360 tgttgatgta cgttataaac ccgttgtcgc cccggctaaa cagggcgtat tcctcagtac 57420 catccttgaa cgtatctaac gcgataatat acttgtcgaa gatcatagca tttcctcccg 57480 gctgatgtag tagttgtatt catcctcttg gacgaggaat gctcgataga atcccttctc 57540 gaaatctcct ttgaccagta ccagatttcc atccaccttg caggtgtaaa tgtacatggt 57600 gtttgctact cggataaccg gatcatcacc cgggcgaaca tccagagcag ccaacatagc 57660 ttccattggc atgcttgtca agtgagcaac cacggcggag cagtattctg cgtcccgtcc 57720 cgaggtatcc tctgcataag caggagcgac cccgcatgaa tgcagggcaa gtgtaaacgc 57780 aacggctacc aatttcttga acatactaac cctcctcttg atctgtctgg ggaacatcct 57840 gcctagggta gacgaatgtc tctggatatt tcatgcatct tagctcatcc ttgcagaatc 57900 cgtcaatcag tttttggtgt gcgaattcgg ctgctctgta gtaccgatta gcctgtctag 57960 cctcaacccg caggaggtgg cttatcgtgt gagcattgat attactaagg cttgcaaaaa 58020 ttgtcaagag cttctttgca gagaggggga ttgacctttc gtcaggtctg taccaatcaa 58080 gtctggccac tccttggaga acgtcgtcca cccacagagg gtagtctcca tcaagctcga 58140 ccatgacttc gtacatttca ggctgaacag cgttgaaaaa gaaagagggc tttcgccctc 58200 tgctggtatc tagaggagga acaagccccc tctccacctt gtgaatcaac cgatcagcat 58260 tcgcccctat ccgagacttt agctcctcga tctcttcaca tgtcaacata cggagggcac 58320 accttagatt tctcgatagt gaacacgcct tcgcatgtca ggttagcagg tccataccac 58380 ttgaacatgt tgttgatatc gtatcgaatc aactggcgga acttctgccc gtcgcacata 58440 tccacgtcga accacgccac gacccatctg acgtaatctt cagggtcgtt ctcttctcgc 58500 catctgcact ctagatcaac gtgactgggc tctagaacgt aaatgtcttc gaaccctgta 58560 ctctggttgt tcttaagtcg gatgattcga gcgcgaatcc attgcatgca cctgcggttt 58620 gggtctgtga tatcgcagac taccggaacc tctggaacct caactgtata catgattgta 58680 cctctatttg ttttacaaga acgccatgat tctgtctctg tctgcatggc ggtacagatt 58740 gaagcaaggc acgcctctag aggacgccag ttgccaagcg gtcctagtcc cgccttctgg 58800 aatcccgttg tggtctgtct tgctccagca caccaagaac ttgctaggcg tgttgagatc 58860 gattcccagc acttggaaaa cgttccgagt gtgggctcgt cttgcgaacg ggcttagaac 58920 ggacctcccg tcatttctga cagagttcca agccggatga atttgactgg caatgccttt 58980 agcttcttcc cattcagccg gcaactcttc ctctggcagg atggtagctc cgagcgtctc 59040 cgttatctgg tactggttga agccgggaga cggaagatag atttctgccg tagttcctcc 59100 cttgttattg gatatataat ccagccagcc cgattcgaac gctgagtccg ctcccttcgc 59160 tcctcctgac cgaagaataa aaccttgttc tgccagttta cggcctacct ctcgaaggat 59220 gccccactct ctgtttggcg tatccctact tccgactcct gtgtaatact tcataagatc 59280 accatttcgg atagctcttc tggtgttacc cattgatgcc ggtattctcc gttcttcggg 59340 ttagaatatt ccaatagaac agggtaatac tcgtctcggt aatcggtgtc tataacctcg 59400 cagttccaac ctacagggat aggacaagaa cgccccttgg gggccatctt agttccaata 59460 gacaacctgc cttgactagc cgcctcattg acgcttatca ggctgtatct gtgttttaac 59520 gcttcaacta ccttgacttg gaggtctaaa agttcctcga ttgtaaagtg gcttacatcg 59580 attgtcatat tactccctcc cttccagttt cttgaattct ttgtccagct tagctagatg 59640 cttatccaac ttgtctagct ttttatcctg ataaagctgg aaagcctccg agcccggggc 59700 caaccaagtc cccttatact taattgcacc ccggatcata tctcctccta ttacagttcg 59760 taaacgtata cctgaaactg gccgagcgtc tcctcgataa gaggctcgac attgctccag 59820 tcctctccgg ctaaaccgca gccaatcttc ggcagaccta cacacaactc cgaggtagga 59880 atcgcccgag cgtcagcctc tgcctcaagg aacagagaca tagtgtacag ggcttggccc 59940 agtgcgtcaa gctgagtgta gactcgtccc tcttctcggc catagttgta ctgcccgtac 60000 agattgtaaa tcgatccata ctcgttaatt gtgaaggtga gggagccgag tttgcctcga 60060 tcccctttca ccgttgcttg gtctgcctcg taggcctccg ggaattgctc ccggatttgc 60120 ttagcaatgc cgctgcccat ggtgttgaag caattagcct gatgtgcaat agcgtgcaac 60180 tctttgtttt tgaacgcggc gataagatcg ccctttcggt atttaatcat ttgaacctct 60240 caacacttgt gaatctgact tcagagcctc tcgctccgtg agcaatgtcc gcgtacattg 60300 agttaatggc cgcaaacgga gaccaatact ccttctccca gattttgaac ttgaacattt 60360 tgtgcccttt attttctggg tgaccttgtt cgcagaaggt tgtaaagtaa tatttagcta 60420 acacctttat cctccttata ctccgttctt aatccgatag cggatagatg ccaagtcatt 60480 attcttcagg tcttcggtgt cccatttccc gtctttgaag aacgtccgca aggaaccagt 60540 agcctcctcc tcttcagata cattgtcctt caactgaagg aatcgtccat tttgcaggtt 60600 tcggtacact ttcaggagac ctttagccga cttcttcttg ctgtcagttt tcgggtcttt 60660 gaagattgca atgccttccc cgttcacttc cgtgtaggtt gctttcactg caaatccgaa 60720 agtgtctcgg gtgttgcact ggtaggtgta actgccaact ccaaacacta cgttcaggga 60780 agcgaaacct ttctccttca agcgctccaa gattttagct gctcggcgag tcgtaatgga 60840 atccccatag atcaaaccga tatgagaatc gagcatctta taacctgctt cattcacagt 60900 accgccgaag gtttcccaca gaacttggat agctcccttc acctgcgcct cgctcacttc 60960 ttcaagttta tagccaatta catactcgta ttgatcccac tcagtgggaa taaccttgaa 61020 gtacttatct tcaaagttca gaacaaatgc atcgtttcca tttactgcat ccatgatatc 61080 ccagtgttcg agcgactcga caacttcaat atcacccagt ccgcagataa cctctacagg 61140 atcaccagag tctggacgaa taaccagctt gccatcacgc tccatgatct gatccttgat 61200 ggacggcaga atttcagtaa gcacgcccca gaagtcgaag ctgtctgcca cgtacgacag 61260 aataccactc gggaacttac ccatcagttc gataaggaat cgacgttctg cttcctcacg 61320 gccaccttca ccttccccat cctgcatttc tttctcaata cggaggatgt tactagtagc 61380 tacagcgtgt tcagtcgcag gaacggagca agctaccaaa ccagtcgcgt tatagtagtc 61440 ctcagcataa atagctgctg ccaatgtgtc cgaacctacg aacgaggtca agtgaccaac 61500 accactacgg gctgcgtctt cgatcccgct cataccccgg gcactgaagt cgtgaaactg 61560 aacggacagc aggaagtcgt cgtagcaccc agtgtggttc gcgtagtacc ggcccatagc 61620 tgcgtattct gcggcaatgg ttgcgttggt tgcggtcttc caagtcatag ccgaaatcag 61680 ggtctcatgg tagttcacca gccagtagaa ctcaggcagg gtattcttga tagtgagcac 61740 aggcacgccc ataggaacgc taacgccctc ggtcaaagac ttaacctcca gaggcagata 61800 gccgagcttg tgaagggcgc gaagctgctc cacggcttcc atttcccggc caaaatagcc 61860 agtcaggaac cgggaatacc ggccaacggc gttctcttct tcagccgcga agaagccttc 61920 ccaagactct acgatctcca tccaagcggc ccgtccgccg acccacttga gagtgccgtc 61980 gtagaagtcg gtggcatgcg tctttcgata aatcttatcg gagcgagggg tcaggttact 62040 atagacaagc tgagtccctt ccgagtacat ggaaccgtgt ccaatcttat aaccatcggt 62100 ggaaagatgt ggcagaattt tcatgttatt tcctcctgtt gtgttgaata ggcccagact 62160 acatcaatct gggcctcctg tcaatattcg acttcttcta ctggcagcgt cagcacaggg 62220 tagatgcatg gaaggcgcag caatggttgc ttcttgctgt ggaagtcttc ccaaaactta 62280 tcgtgcatcg tcttgtaccg agcgtccagt tcctccttgg tgtcgaactc ctccaccttg 62340 acaaccctct tctctggagc cgaacgctta tactctacaa tccagatact caagctcaca 62400 ggcgttccgc cttggagtat tcaaccggaa tgacagtcag cgcttcgtgc tctttttgag 62460 ggagcgtatc cgaggtgtag atgcatccga aggaatccag caagcagtcg atacccttac 62520 tgaagattcc atgagtgacg aacaggtcag ggagcacttt actgtactct cttagggcct 62580 tagacacgct tcggaatgta gcacctccgt cacagatatc gtcgatcacc agaagcggaa 62640 gttcaggatc aatatccgaa ggattcagaa tttcaaagcc ttcgattttg ccggtctgaa 62700 gatcgcgctt cttgttgcaa cgaattacag cggctgctcc ggccttcttt gcaaaatcct 62760 cggtccgctt tgttgctccg atatcagggg ctacgagttg atattgctcc cactctgaac 62820 ggctcagtag gccaccgaag accgaagatt gacggacaac ttcgacgttg ttaatcaggt 62880 gcagagttgc gtcgctgtga gggtccacaa cgataactcg gtcatatccg gcagagttca 62940 gcatgtttgc aaacactttc aaactgaagg cgtcgcccgg attgcaccga cggtcttggc 63000 gagcatacgg gacataaccc agcagaagag tcatgtgcgg attaatcatt tctgctcgga 63060 tcgcctcggt gacgttgaga agagccatga tatcatcact attctgaatc tgagctttaa 63120 cgtttacgaa cgcatggctt tcgatgccgc ccacattaac gcccacttcg ccgcccggga 63180 acgtccacac ttttgcctct tgccacggac ggctcataac accttccatt tcctgaaggc 63240 aacctacagc ataactaatc atacatcctc ctcacagttt cacagagaag cgattccgca 63300 ttgcttccat cgtgctctcg ggaacatcgt gtacagactt attcccatga cgattctcta 63360 caatcagaga gataacagtg tagccaaact cttcagccat gtcaatgtat ggtgctacct 63420 ctcgctcccg ggtactagta ttggatacga taaccgcatc tagtcctatc tccatagacc 63480 gtcgcgcttt gtccatgcac tttttgtgag attcaactac cctctcagct ttccacacat 63540 acttgccgaa ctccatttgg taatcgtccg cttcgcagat agacgcctgc cggcctgact 63600 cccaagtttt gttatacaga atctcggcaa gagaggactt cccggagccc gggagtcctc 63660 gaatgatata catgatcttt tcttgcatac ttcctccttt aaattcgatc catatcgaag 63720 taggtttcga tcagaagtcg tcgctgtgca tcggtcattt ctgagaaccg agcctcatcc 63780 acttcattta ccaagaagtc taccagagga tagaactctt cgtcaagcgt ctgcttgaat 63840 ccagccgggt cttggtacat cgcattgacc ttcttactac ccatcctcat gataaacttc 63900 ttgccgaggt agtgagttga cttgcacttc actgtcccta gccctgtttg taccatgtaa 63960 ccttctttct cacaagaact cagaagaccc tttgcatgtt cccagctaca ctctatgtgc 64020 tctggacgaa gaatctttac agaactgtgg tccgttacac ctagggcgtg agagtcaaga 64080 atatattctg aaagctggcc cccagtgaag atatcgcgga taccgatcaa atatgcccct 64140 tcttcttcct cgacaatgtg agggtcgtct ggagagcata tctcgaagtt atatgtgaag 64200 cctgcgatgt aatcatctgg gttattcgac acatacttct gaccaagggc aacgtaatcg 64260 ccggtcaatg accccgtagt actgaagata agggagccat tgtgcttagt cacggagaac 64320 atgaatccat tcactttctc aatcagccgc acacggaatt taggatggag gaaactccca 64380 gcaccattct ctcccagatt aaacaccttc tcgaaggggc gtacaataca atcaccggag 64440 tgctggtcaa atacatgacc ccgtgcctcc agaaggagcg gatgctcatt ccacaggttc 64500 tcgtagaaca ccttccgggc atactttata atcgacatac cgttgaagtg cttaacagtc 64560 accagcttat tagcgatcag gtctttgtac attgcaatgt tgagattacc ttccatccta 64620 cttctcctta tttcaattcg acaattgggc agaatttagc cttctttgcc tttagatacg 64680 ataccagaat cccatccttg ctggacgatt tactcgacat aaagcgagag aatcggtaga 64740 aaacccacac gccataaaag acggcgatga ttccaatcca tacaaacccc atgacagcca 64800 gagtcccacc tagaacatat ccggtaagtg gaccgagagc cagagaatac aatacagagc 64860 ctacaacagc agcgagcgct acaaccgtta acgccagcca cacgacgagg aatactgtct 64920 gccagaaata agagcagagg gttacaattt gccaaccgct tgagatagcc gaatagaccg 64980 gggtctcgaa cgtacgatgg agccgcatat gccacgaatt cttatcaatc ttcatgcttg 65040 ttcctccggg aagatgttga agttaagtac gttatgctct tcaagttcca tggaggctac 65100 catcttataa cctccgagct tgtgaacgat ctccagtata ctctcaatag agaatttgtc 65160 aacatgctgc ttcatcagat tggagattcg gctctgatgg gttccacacc gctctgccac 65220 ttcccgttga gtcagcccag actgagtgat gtagtgtgca gcaacaacca ttacagtttt 65280 cttgaaatcc ttgaccggat cattcatgtt agtcctcctt attgctcagc gttactttgc 65340 catcgaatac tcggaattga gcgatctcaa actgatccgt ccagcgggcg tcctcgaaag 65400 ccactccttc aaaagtcccg tcttgtttaa catcagaagt catgaggacg ataaaaggaa 65460 ctccgtcgtc atggatcagt tccaccagag tgttagcttt aggtttaaca tcctccttgt 65520 cacgcgaaat caacacattg accattcttt cctcctttta tttatggtgg tctacaacca 65580 caaactcttg ctctcgcata tattccctca cttcgtcgta agagaatacc tgatgatctg 65640 ggtgattgtc aatacctaca tcaaggcgct tacccttgga aggcaggctg ccgtgagtgt 65700 ggccgtgcag gtgccaagct ccatgatggg cagtattcca cgtctcgaaa ggatagtggc 65760 acatgacgat cttaactccg tcaattcgaa tctccttgta ctcacgaatg tcttctacgt 65820 gcgataggtt gctgtcttca atcagcttcc acagtcggct atcacagtga ttacccttga 65880 ggaaggtgat ccgaccgttc aactgtctaa tgatatccag tacagcttgc agcttgttct 65940 tacctgcgaa agcgaaatca cctaagtgat acacttcatc ccgaagacgg acccgagagt 66000 tccaccgaga gataagctcc tcggtctgct cctcgaaagt ccacggcctg ttgcaatact 66060 cgatcacatt cttatggaag aagtgtagat cggaagagaa aaatacagac attatgcctc 66120 catttcaaat tcgtaaattt tgttaatcct gcggatgagt cgcatagcgg cccctcccag 66180 cagatgttca cgctccggct ccatactagc catagccttg aactctgata acatatcccg 66240 acgctcgtag tggaaatcta ctacccagta atggtccgca ctaatcttac cctctcggta 66300 cagatgccct tcgacaccca gccagcgatc cactgcatct ctcttcagta gctctttcgg 66360 agaccacttg tctacacccc gcaacttctc gaagaaagag taaggacgag aatagttgtt 66420 gatggcttcc tctacagccg actcagcctg caatttaatg aactcccatc ttgcaagaac 66480 ttctttaatc tcctcggtgg tgaccggggt gtagctgtac tgttctttat attcattcca 66540 cactgtactg ttctcctaca tagcctttga atttgtcgga acgagttgtc ttcttctgtg 66600 ccttgttttc cagaaccgat gcttcccttt cgagcatgct cagttggttg ctatacttct 66660 tgatccgttt cgcattgcca ctcatcacag aatttgtaag attggcaata gtgtcgcaga 66720 ttttaacctc ttttgcaacc ggatgattac ggcaaccctc gatatacttc cgatagcttt 66780 cagctcggtt tttgtcaaga atgaccagag cctctacgat atgcggcatc acgcccatag 66840 actctaagtc ctcctctgtc aggtcggtat cctcaagaac gtcatggagg aagcagaccg 66900 ctagaagggt gtccatgtac ggaaagtccg agaaggcctg attcgggtcc atatccttcg 66960 gagcattacg tgcgacgcag attgtatgca cttggttcag atggtaggca tacggatagt 67020 tggtctctcc ataccgctga ccttcatggg ccgagagtgc gatctcgata gcaataccga 67080 gctgagtttt catgttaatc tcctttgtag aatgtgtggt tgcctatctt gatggtacgc 67140 ttgtacttcc gagcccaccg agggagcctg ccattattgg ctctccttac ctttctctcg 67200 ttcaggtagt ggtccgctcc tcccgttgga tcaacagtat acccatacag agcgttgtat 67260 gcaacatgtt ttgctgtctc ccacttgtcg ggctccttga cgccctgccg catgctacca 67320 tcgcaggtgt acgaatattg acatttgaag tataacactc cagctacggt gctgggccac 67380 ctatcgtgct gcatcctgtt gatgacggta tgagctacag caatctgccc gatttccggc 67440 tctccacggg cttcgaagta gaccgcttct gccagcagtc tgcaaggctt tctgtactcg 67500 cacagtgtta gcttgctttc tatgatttga tcgggactgg cttggaactc cactacaggc 67560 tccgtgccgt attttagacg agagtattcc atgtcgagga acatcccaat gaaggctaga 67620 aggatcgaca aaacgagagc ttctaaggtt tccataacac ctccttagac aaagaagccc 67680 gccttgtggg cgggctgtat atcactcggc tattatactt cagcccaagt tgtaacgacg 67740 ggcgtagtct tcgttgggga actcgaccat catcgactga atgtgaatgt tgcctttacg 67800 atccttctgg attttggcat ttttcacaat cttacaggcc tgcgccttag ccataagctc 67860 agggcttaca accagatcga tgaaccctgc actccgatac ccgcatccgg caggggccca 67920 gaagccgtgc tgggtcatcg tcgagccggg aacgaggtac aggttgtgca gacgcacagc 67980 agtgttgaaa ctcagcttgc tgatatgctt cgcttcccga gtttgggttt caaaacaccc 68040 agtcgtgtag ttgaatttgt aagtgagagc atccatgaac tgaatgacgc ttcgaatctg 68100 gatagcagaa gtatccaaga gctggaactc ctcagccgcg tcgattgcag tggtcacgtt 68160 gacagactta gcgttgaaca ttttatatcc tccttattct tcagggacaa atacaccacc 68220 gattacccgg ccagcgcgaa ttagtttacc agttgggaac tgagcacgca aggtcttttt 68280 gaaacgactt tgaatttgca cagttagcca cttaccccgg tagttctcaa aattagtgat 68340 ctgatccttg cgttcgtcaa agtcaccgta cgtcacttca agcagctctt gaggtacagg 68400 gtcaaacacc accagaacag cgttcccatt cttgtctacc acgtagttca cgatctgcat 68460 ttccatatcg aagaactctt tgtacttctg gagaccgctg gagcgcttac cagattcgta 68520 caagccctct gggctgcgcc acatgatacc ctcataaccg ttctgacggt acacgtcgtg 68580 aagacgtttg aggtcttcga aagtggagca gaatacgtac tcaacgaatc gaatactccc 68640 cagatcactg tgtagtgcag actggaactg gaagtctacc agacgctcct taaatgtcaa 68700 gtcatctttt acgatatcga agacatggaa ctccatccgc ttacgaagac cgtaaataaa 68760 ggacgtgctg tccacttcct tcaggagacg atcatactcc tcctctccgt tctctagagc 68820 gtaggcgtca agagccttct cagccttcat ccacttatcg taggcatcct ctcgcttgac 68880 cgccgagttg atatcctcca gcacctcacc gtggacgtac agttcgccgt cccacacatc 68940 accctcttgc atgatctctt cgagttcttt gatgatgtgc ggtacattgt aaggtttacc 69000 catgcgagac gctagcgtaa ctacgccatt ggctttctta gccatgcaac gcaggccgtc 69060 tagtttagga gagccatacc cctctttgta tttagcggga tcaagcggtt ttgcgagcat 69120 agccataaca gggagatcgt tgagttcttc cttggttgca cgataaccct tgtccaactg 69180 cttgctcacc ttggactgag cctcagacac ggcctgctcc tctacagagc gtttctgctt 69240 accaactcgg atgttggtaa cctgagaggt catggctcca tgttctttgc cgtatttcac 69300 gacgatattg aagctaccgt cttcctctcc gaccacctct acagtccact ccttgaaccc 69360 gcctttcttg tcgagtccat acagtcgttg aaaataactc attgatcctc ctcgtatttg 69420 atgacaagaa catcattctc ccgtaggtgc ctaagacctt cgtcgagccg atattcgtgc 69480 ttatagtaca ctactttgat cccagcttca accaccgaga tagcacaatt tttacagcaa 69540 gagtgagtga cgaacagggt agccccttgg gcactctcag ggctgcgtat aagggccctc 69600 agtgcgtttt cttcggcatg cctcacctct gccttggtta ctcccgtttc gtcctccagc 69660 ggcccgttta agtgctctgg aagggcatta tacccgcaac tgatgatacg gttacgtttt 69720 actagaactg caccaacctt ggaacgagtc gagtcgctgc acttagcgaa ggcctcagcg 69780 gcctccatgt aagctttaat atgcttaacc ttcacgacta gcctccaatt agaaccgcga 69840 tctcctcgta gtacccctct tcagggcacg cgaattccat gtagtactcg tcagtgtctg 69900 tcaaatagac aacgctaggc gggtaatagc tccaagtcgg gtctccgtgt tcaatctccg 69960 ctaccttcaa gttgccatac acagtgcgaa gagtctgtag agcctcgatc acatcgtcga 70020 tgcgcattac agtgggttca gtcggttcag tcatatctcc tccttagttt tctactttac 70080 aaacggcatc gccccggcga aggaacactt gcactgatgg ctttccgctc cacttgtccc 70140 acgcttcagc tttaacactg acagtcttag gattgattgc aaccacctcg cctaccagca 70200 taaccattcc agttccgcct aggcagaatg ctactgcgtc gccgatctcg atatcccttc 70260 ctgctacgtc cttcatttgt actctccatc tgcacccttg attaaaataa cgaagtccga 70320 gggatcatca ctgccgtagg cctttgcccg aaactcctgc tcgtatttat tcaccgcctc 70380 cggatcactt ttaacctcaa gctcttggta gaggtcttcc ataaaccaac ccaagtccgt 70440 ggtcgcagcc gaagccgaga ggtgaccaag aagtcctacc agcatattga tctcgtcgct 70500 ctccaactcc aacttgtgac cgttacgttt tactactttc atatttcctc ctatcgcttc 70560 tgtccgctta cgtcaaagta cgatttccat tcttctccga atagttctct acccttatca 70620 tcgtagactt tatgagcctc ttctgctgtt ttatagcaac cgaggtaaat tctcttacct 70680 tcatacctga tccgggcaac gtacctgttg tttctaaaaa agataccggg atacccgttt 70740 gtattacggg tagacgcggg tttattctgc tgctgctccg agtccgtcgc ccaccggcaa 70800 ttagacttgc aatacccttt tgtcgagtcc tttctatcga gagtcttttt ctcgggtcgt 70860 tctcccatgt cctcatagaa cccctcgaat gtcttccact taggatcgat ggtaacatcc 70920 ttataatatt tgtaactctt gtgctttggg ttcgtacatc tgtcgatcat tgtcctccaa 70980 gaattgtatg tcggagttcc gtacattcca tgggaggata gtagtttaga ctgcatgcac 71040 ccgcaactct tattatctcc taccttgagt gctccagttc taattttcaa aattgccccg 71100 cagatgcatt cgcatagcca aagaacctct cttgaattac tcctcgctcc agagtctccg 71160 actaccctga gatatgtgaa tgtctgccct gtcaggtctt taactgccat cctacctcct 71220 tacttgacga gtggccacac cgtaagctgg cttgctcccc tcgcccgtgt tgtgtttctt 71280 ctgcactcgg ctggcattga cggtgtaacg ccctttgcca tactcttcgt ctatccacgc 71340 ttgagcctta gctcgctgag acgtgtggac aaagatgtag tagccagatg catccttgat 71400 gaaccaagtg gccgggggct ggaagtccag acgtgaaaac tcttcatagt cgatcacagt 71460 caccttctgc ttagccactg tgtactgccc cactaccgac tcttttgcaa tgattttatc 71520 aatcatctga gttgaaagat cagagttctt cgaggtcaat ttctacctcc tttcctagtc 71580 cagtatctgc aaagaagcta tcgagacaca gagagtggta ttgagacact ttgtaaccac 71640 cgcacttcag taggctgtga gcagcctctt ccaccttatc atctgtcagt ctccagcacg 71700 cccctaggag tacttcagct aactgatcta cacttggagg gttctcaacc cacagcccca 71760 ttctattgtc aggctcgtat tcttcttccc atacaagttc ccacactagg ttactcactg 71820 atatacctcc ttcttacgaa tagaatacat aacccactcg tcttttcctg tcttcccgca 71880 cggaatgtct atttcgcact ctgcgtttac aatcaggtct gctacaatgc agtcaagaag 71940 ctcctcgtct ggctctggta agcccgggta ggacgatata accctgcgga tagtctccgc 72000 tttggtattg cccagtaccc cgagcatgtg gaggtcgaac tctccactgt agtcatccca 72060 gagttgtcca aatatcaccc atacactatt catacctagt aatcctcctt cagcttgttg 72120 gtgtccatta ggcagcctcc ttcttcttgt ccagcaactt catgcatcgt ttgcaggtga 72180 tatgattgcg gtagcgggag aagttcttct cctcgaagtc gccatcggtg ccacagaaga 72240 cgtcatatgg ttcttcactg tccgcttctg tgccgccgtc ccactcgtcg tagtgaactg 72300 ttcgcgtcgc cattcacgtc acctctattc cggcttgctg gagggcttga gtgatccggt 72360 cagttgcata gcagtaaccg gtatcgaaat tgtctcggca ggagttgggc cagtctcgct 72420 ggcagtccgc gatcccatcg tccggcaact ccaccctcag agccgagcgg ctggcttgcc 72480 aagcgtcaaa tgcgactgcg cgctttgatt taagaacctc ggcggacctc caccacgctt 72540 caaactcgtc tctcatactc cgcaatcctc ctgaatctct tttagcagct cggaaggcat 72600 aaccgacagt gccagttcct ccagagcatg gatgtaatcc tcaacatatt tccactcctt 72660 tctgatcttc tgaaggtaca cgccctcttt actgttgtca atagcctgac ccttcagttc 72720 ctgcattagt tcgaacatct tgtatatcct cctttggccg aaaaaatggc cggcgactac 72780 tgtcccggcc tgatgatact actctgaaat ttcttccatt gcaaggcgtt tcttttcaaa 72840 gaagtcactg agcttatctt ctagctcttc gccaccaatg taaagctctt cccctgcctt 72900 tacacgctct agctccttct cagtcaagaa gtcgctgtag acgtgatcta cccatttatc 72960 gcaccacgct gagctaaacg ctgcattcct cagactattc ctgaaatcag cagatacaac 73020 gccaaaagaa ggcgcgtgga tcatgaaata tgtgaactgg tcgatctcaa cggagtcgca 73080 ggctagcgcg atggcagtca tggcagacgc acactcacct tcaatacgtg catgcactgg 73140 agcttgacac tctttgatcg ctcggattat agcgttggcg gtctctacct gtccaccgca 73200 tccgttaatg gtgatgtaca cttcatcatt ctgacctgca ttttcaaggg tccaaagctc 73260 ctctgtgagt tcttcgaggc tcttgattac gtatggcaga aggatggagt aacgattgct 73320 aacactttgt gtacatgaaa caggcataat acctccttta caaaaatggg cccgaaaggg 73380 cccttattac tgaatcactc ctcgctttct ttctggccag agcccagcat tgcaaagaat 73440 ggaaggagga ttgtgctcag ctctccgctg acagcttcac caacttctgc accagcctga 73500 gctacactca ggaactcttc agtgcgtaca aacttgtcaa ccttgacgag ggttttaaag 73560 tctactcgtt ccaagaacgc agtcccggct gcttccgcca gaggttcgag gtttacgact 73620 tccatagcgc gatccagagc ttcctgattg atctctaggc cgttctgggc tgcaacctgc 73680 atcagggtag acttcacagt ctggattgcg tagtctttga aaaactcacg ttgtgctttg 73740 ttaaacttca ttcacttttc tcctttgtag tacgacgacg gcgggttttt ggtttatctt 73800 ccgattcagt ctcttggact tcctctacag gaacttcctc agctacttct gtagactttt 73860 cctcagtctg cttctctgcg ccttctcgga ccatcttgac agacttgaga gcgaaattca 73920 tattggcgaa atgagggtct tcgagatcaa tgcggaaacc ttgatcgaaa gcattttgca 73980 tgcccatcag aaggctgaaa acgtcccatt cttgcacaat gacttcattg ccgtcaagct 74040 ctttttcgat ttcctcagaa acgccctctt gacggaacat ctgtacttga cagagggtgc 74100 cgtacacagg gtagccttcg atggagcgga cgactcggaa accttccttc atgtgggcgt 74160 aaatcgagcg aagccagacg atagggttgt attctacgat attgataact tgcatattct 74220 ttttactcct tgcgggttag tgttttacaa taataccacg tttctcagga atgtcaaccc 74280 attttgttct ggtagaggct tgacatagag gaaatctgtg gtattatcaa tattcagcgt 74340 gggagagata tgtctgaaag cactcaccgg cccacgccta gcgcctatga agaggaatcc 74400 acaagggcaa cctgaactcg aatgctgtta aagggtggag acgacgcgaa agcggaatga 74460 cagcaatccg atgcagccta catgctgccc ctcaccgaac tcatctgcat gagtaagagg 74520 aattggatag agccaaggca cgtcttaggc agattaaatt ctgtatggcg agccttggga 74580 cgactctatc cttccctagc cgaatctatc tgcatggggt gttctcctga tacacataca 74640 caaataccca ccacagataa tccatcaatc aacccataag gaatttctat gagatgtaag 74700 tgctgtgata gcgaactctc gtttgagact ccagtcatca ataaacatac tggtaaggag 74760 gacgatctct gctcctcttg ccgtaggttt gctctcaatc ctacactgga tcatgagtat 74820 tttggtggtt ggtatccaag cgaaggggtt accgctcctc tccctaccgg ggactgacat 74880 tgtatataga gtgcgcgtac tctgacaata tgtataaata gtagattacg gtgcgaataa 74940 ttctttaagg gcttgacaac aggagatttc gtgctataat cggagtatat ggggcttaca 75000 aagcttcaga ggatttaata tgactcaaga aagaaacaag ggcggtcgcc ctacgaatgc 75060 cgagctagaa gcccggggta tcattcagac agacctgaaa gcagggctta gacttctaaa 75120 gaagagcttt gcagagaaca tcagattcct ccaagagcaa tctgacaacc cagaggtctc 75180 tctacagatg agaatcaagc tcaagaaaga gctttctgac atgttcgtcg cttactacaa 75240 agctgacatt gcactcaaaa aagagcttgc aaaaggaaca gaatcaggag ataatgagaa 75300 ctctgaagag gacaagactc ccggagtcgt tctcgcgttt tgattaattg ccgcttcgtt 75360 caatggtagg acgccagact ttgaatctgg agatgatggt tcgatcccat cagcggctgc 75420 caaatgtagt aaaagaacat tcacccgaca aggaatgtgt ctcgctcaga ggacagcgag 75480 taataagtgt cctccagaat taagggtcgg tgagcgtaat tggcaaccta ctggattcca 75540 aatcctcgta ttctctgttc gaatcggagt cggcccgcca aattaatgtt gacaggagag 75600 taaggctcct gtatagtgtc acaaattgct cgtatagcgt aatggaaagc gcaacggtct 75660 tctaagccgt aaggtctagg ttcgagtcct agtacgagcg ccaaatttaa gatggacgga 75720 agctaaagtg gataggcatc gggcttttaa cccgactata gtgagttcga gtctcacccg 75780 ttcaaccaga tttagtgagt aaatcagata ggttctgagg ctccctgcta aggagtacgt 75840 ctgctaacgc ggatgtggat cgagaccact gctcactgcc aaaatcactg ccaaaataag 75900 tgattttaag tgttgacaaa ctgaattttc catggtttaa tacacttatc agatcaagaa 75960 acaattagcg agtagccctg agtaggtcgg gaactagtct agaaaactag gccactgtga 76020 tgaacggtga gggttcgact cctttactcg ctgccaaatt aaggccctgt ggtggaattg 76080 gtatacacat cagtcttaga aactgacgcc gagaggattg agggttcaag tccctccggg 76140 gccaccaaat taagaatctc ttttgctatt tggttagggt tcgagtccct acccggcgac 76200 tatggccggt ctatggcggc caaatagtga gagagctagg ggacatgacg aaggtagcgc 76260 tgctttccga tctccccggc gctataaaag ttatcatgaa ggggttgaca aacaagaaat 76320 tcatgataat ataggtacat agagtaacaa acaatgtagc cgggtagctc aattggtaga 76380 gcacccgacc gataatcggg tggttgaagg ttcaagtcct tctctggcta ccagaattta 76440 aaggcccatt agctcagtct ggactagagc aagcccctgt ctagggcaag gtcgtcggtt 76500 cgaatccgac atgggtcgcc aacaaggtcg ttgtagagat agatggctac tatcatccgg 76560 ctgtaacccg gacgccatag gctagaggtt caattccttc cttcgaccac caaatagcga 76620 gagcgttaag actggctggc gctgtcactc ggctcataac cgaatacaag tggttcgatt 76680 ccacctctcg cttccaaatt gcactccgag gaaccctaag tggtgggttc agtgtcgcta 76740 cctatctcgg taaggggaag cgcctaagct ggcacgggta attgagtagc tgtgataagc 76800 tactggcagc cagtataaat cgtccggctc gggcccgtta tagctcctag atttgaatta 76860 gatgctgtaa gccataggag gtgatccagt atctcccgga ggggcccggg ttaacaacct 76920 catgaattta gcccgcgttg gccgagaggt ttaggcggcg gattgcaaat ccgtctcaca 76980 tcggttcaaa tccgatacgc ggctccaagg tttatattgg gatgtagctc agttggtaga 77040 gcagggagct gttaactctc aggtcgcagg ttcgagccct gccgtcccag ccaatttcca 77100 aaagagactc ttcgctttag aagcagagtc gaacgcccga tacgggcctt attcatctcc 77160 tcgtagctca gtctggttag agtgtctgat ttggaatcag aaggtcgaag gttcaaatcc 77220 ttccggggtg accaattaaa gcgggtttcg tatagtctgg ttattattct tggcttccac 77280 ccaagagact agggttcgaa tccctaagcc cgcaccaaaa gtcgtagacc tcagtaaccc 77340 ggagtaacgc ccgggagaag atgtgagttc tacgtatacg cgtctgaagc taactaggta 77400 gaagcaccgg gttgaaattc cggaggactt ggatcgttac caagcgggcg caccaaacaa 77460 tgcagttata gattaaatgg ataaatcgcc agactttcaa tctggtgttc cgggttcgat 77520 ccccggtaac tgctccaatc aagtccaagc cggaacattc ctccgtatgt gctttcagcc 77580 ggcttggcat tattcgtgtg gagattgtgt agcccggatg ctgccttccg gttgtgaccc 77640 ggttgttggg gttcgagtcc ccgcctccaa ccaatgttgt gtaatggaac tattacgttg 77700 acgctgtgtg ctctccggat cgtaagccgg taaagcggga atagcgggct cccgtagcag 77760 agtagtagtg tggttcgatt ccacagcacg acacctttcc tcctcgcctg tgctgaacgg 77820 tttcctcctc ctttcccgtc tcacaggctc tattccctgc cctttaagca tttatggtga 77880 tgcaccggct ttgtaacccg gcgaattctg ttcaagtcag gaatggggca ccaattcact 77940 atcaaagaac ccgcaagctc ccgatagggt tcacactcta taaggttgta gcatggaaaa 78000 cactaaggtt cctgataaaa aactcggacc aatcgcgcta gcgcttaaag aggccagaga 78060 gaatttcgat ctcagccctc atgttattgg tccaaaatct ttcaaacaga aagagttcac 78120 agacagcgat gcaaagatca ctgtattcgg tggtgctgct ggtgctggta agtcttatct 78180 cggtgtaatg gacttcatga aatatatcca tgatcctaac ttccgaggtg taatgactcg 78240 tcgtactact cctcagatta aaggcccggg cggtctgctt gaaaaagcaa cagacctatt 78300 caagctcgtt gaccctaaag tcaagtggaa agacaaagac ggcaagtttg tgttctcttc 78360 tggtgcagtt attttccttc gacacttcga acaagaatct gacaaagact ccttccaagg 78420 ttgggaggtt agtaagttcc tagtcgacga aggtcagcag ttcacagaag gcatggtgac 78480 ataccttatc tctcgtatgc gtaacccgaa atgctcggtt gttccgcaca tgaagattac 78540 atgtaaccct gattacaatt cgttccttcg taaatggatt gaatggtggc tagaccctga 78600 cacaggaatc ccgatccctg agcgctccgg cgtaactcgc tggtttgtac gcaaaggcgg 78660 taagatgttc tggggagaca ccaaggaaga gtgcattgcc cttcatggta atcccagtct 78720 agcgcctgac gatgaagatc aggtgaagcc tatcagcttc aaattcatcg cggctaactg 78780 tttcgataac ccaatcttga tgctcaacga ccctgagtat gtagctaacc ttgaagccct 78840 tcctagggta gaacgtgaaa agctcctaga cggtagctgg cacgctagag aagagggagc 78900 tggatacttc acaagggact ggtgccaaat cgttccccac ccgcctctac gggtgcttaa 78960 aagggtacgt gcatgggaca tcagcggtag catcgaatcc gaaaccaaca gaaaccccga 79020 ctggacagcc ggcgtgctga tgagccgtac aaaagaaggc ttgttcactg tcgaggatgt 79080 tgtcagagag cgtaggttgt tcggaggtgt tttcgacctc attctagaaa cagccaagca 79140 agacggtcaa gacgttgaaa ttcaaatccc atgtgacccg ggggctgctg gtaaagctta 79200 tgctgcccag ctaattagag acctagcgga tcatggattc cacgccagac cgaagacaac 79260 taacaaatcg aaagttactc gattcgcccc gttcgtatct gtagctgaaa ctaaatcagt 79320 gcaagtcgtt gcgggagatt ggaacgaaga ttacttcgat gaacttgagc gattcgacgg 79380 aagtaaggct atcaaagatg accaagttga cgctacatca gatgcattta atgctctatc 79440 ccttggcagc ttgattatcc ctgatttcct accgcctgat atgactcaat ccaacaaatt 79500 caaactaaat taataggagg cggcgatggc cgagactgaa aaaacagcac cgggtatccc 79560 gcgacttcgc ctaggcgaga ttggtagtac aggccttaaa caagtcaatg gtactattct 79620 ggaagaacgc cgaccagaac ttcggttccc tagggcatgc agaacattcc aaatgatggc 79680 ggaagaccct accatcaaat cagcactcga tctcttcgaa atgatgatga gcagggttga 79740 ctgggaagtt gatctaggag ttgaccccga cgaggctatg aaggcccggg gtaaattcct 79800 gaaagagtgc atgcatgaca tggaacacag ttggtactcc ttcatcaaag aggtcactag 79860 cttctacacc tacggattct ccgtacatga aatggtgttt aagcgacgtg aaggataccc 79920 tgtatcgaag tacaatgaca acaaattcgg tattaaaaag ttgccaatcc gctctcagtc 79980 tactatcacc aaatggttgt actctgaaga cggtagaaac ttcctagggt gtgagcaaag 80040 tcttgccaat gttgtcaatg gcgaccgtta cgtcaaccta ggtaataagg acggaactgt 80100 agagattcca gctaagaaga tgcttctttt ccgggtcgat gctaaacgtg acagtcctga 80160 aggtaacagc cctctccgtg cgtgctataa cgcttggaga tatcgagtag agattgaaga 80220 gcaagagtcc gttggcgtaa cacgcgatat gaacggtatg cctacgctct atctgcctcc 80280 tcgatatatg tccgaagatg ctacagaagc tgagagggca gtctacgaat actacaagcg 80340 agtaattcgt aacattcaaa tgaatgaaca atctggactt atccttcctc aagcgtttga 80400 cccagaaagc cgacaacctc tgttcaaatt cgaactgacc tcttcgcagg gcagtaagat 80460 gtatgataca gatgccatca ttcgtcgctg ggacaacaaa attctgcaag ccttgtttgc 80520 cgatatgctg aagatgggtc aggaccaagt tggctcttac tctctagctg gtgccaagac 80580 taacatcatg gctatggcga ttgaatcgcg gctccgcgaa atcaaagacg tactagataa 80640 taaactcatt cctacgctgt tcgcactgaa cggtgattat agtccagact tgccgaagct 80700 gcaatacggt gagctagatg aaatcgatct tgaagagttc tcgaaaggga ttcagagaat 80760 cggttctgtc ggtggtcttg aacgtgaccg tgaggtttac aacaagattc gcaaagctct 80820 caagattaag cctcgaccag acgacgagcc tgttgatgtg gataatatca tgggtggtca 80880 gtctcaagca ggtaaagctg gagtaggtaa tggtgcatca acatccgcag ccggtagaga 80940 caacgccgct gcaaataacg cataaggaga cagaatgctg actcttgaaa gtgttattga 81000 agctctcagc aatgctttcg gggctcccgc caaggcggaa gaagccccgg ctgtagaggt 81060 cacaaagtcc ctagacaatg aaaagaggat ggctttgttt gtcgttcttg agccccaaga 81120 aggcgactcc acgactgacc tacacgcaga cacctactcc gaagaggaag tagagaaagc 81180 ttgcatcaac ttcaatactc attgcaacgt agctaacatc ttccacaaga ttgaaacaca 81240 ggaagctgag attgtccagt ccttcatcgc tccgtccgca ttcacaactg acgacggaag 81300 agagatcaag aaaggtacat ggctccagtg gtggcacttc cctgaaggct ctgaagtagc 81360 tgatacgcta tgggaaggcg ttaaatctgg tgaattcaca ggcgtctcta tcggtgccag 81420 agctacagtc gaggatatcg aatgaccgta aaagcaaaac gtaaactgac cgatatcaag 81480 tttgaacacg aaggtgctca cgtcgctctg gtcagtaagc ttcaaggtgg tgcagccaac 81540 gggcacacta ctcttatcac aaaagctacc aatggcgtaa ctgaagagct tatcgataaa 81600 gctgctgaag ttacagtcac aatgcagttc cctgagttcc ttcgtaagtt cttcgggatg 81660 tattatgaag atgccgaagt tctctctgtt gccatgggat atggcagaac ggagtatcca 81720 gaactagatc acaaagactg gatcgaccag cgggtcgagt ctatgtccat tcttaagtcg 81780 gtttataaat cggctgacct gaatcaagct ctctccgagc ttacccctga gcagaccctt 81840 tcccttaaac aggatcagga actgcttgaa aaggctctgg aggtagtctc cgagcaatcc 81900 aatgaaaatc catccaagga gattaccaac atggaaacta tcctgaaatc ggcccaccta 81960 gaagctctag ctgacgctat tgcagttgaa aaagctgctg gtgtcgctgc tgttgcagaa 82020 gttcagaagc aactagacgc cgctaatgta gagcttacag ctcttcgtga aattgtcaag 82080 gctgctgagg cagagaaaac cgctgctatc gctaaagccc gtaaagagca actggctgaa 82140 gtcctcccgg ctgaccaagt agaagatact ttcaagtctc tggaagttct ggacgatcaa 82200 gcttttgcac aaacagtagg aacgctccgc attcttaaag ctgctgctga ccaaaatgac 82260 atgcttgtcg agaaaggtgt atcgggcgct ggggaagaag acgactctgt tgtcgccggt 82320 gttgccgcta tcctgaaagc tcgccacggc tccaagtaat atctagccaa tctagaggaa 82380 ttccaaatgg ctcaaaacat tatcgcaaaa gatcatcagc gtcttagcaa ctggctgaaa 82440 gaagaacaaa tgggccaccg tggcctgttc tacactcgcg aaactctgcc tgtcgctgac 82500 attgatgtta aaacaactgg ttctgtccta gacagcactg gcaagctggt aactaaggct 82560 actatcgccg acgctaccta catcctaatt accgacctgc acgactatgc caacgctcag 82620 atgagccacg ctgtcgtcct tgctcgcggt tttgccaaga tcggctccaa ggctgttatc 82680 ttcggtgctg acgttgacga cgctgataaa gctaccgtct ttgaagcttt caaagccaag 82740 aacatcttcg ccgttgacca gatcgaaggc gcattcgaga acgtcacctt cgcgtaagcg 82800 agggtcgttc cagtaaataa acactaggag taactttaaa atggctaaca cccgttccta 82860 cctaaacgat ggtcagttct acattgccga ccagactgaa aacctgctta tcatcccgaa 82920 cacttggacc ctcgtcgaga acatgggcgt cttcacaagt gaaggtgtga ctcagaacac 82980 tgtccagttc gaagagatcg aaactcgcta cggtctggtt aaggatgcca tccgtggaac 83040 tcgtcaccaa gttgctagcg accaacgtcg tcaactgcgt gccttcgcga ttccgcactt 83100 caaccaagac gactacatca ctccagaaga tattcaaggt aagcgcgctt tcggtgctga 83160 ccgcgaagaa actctgaacg aggttcgtgc tcgtaagctg gaaaccatcc gtcgcaactg 83220 ggctaacacc gctgaagttg cttccgttag cgctatcgta actggtaaga gctacgcccc 83280 agccggaacc atcgagtacg actggtacga cctgatgggt aaaactcgta aggttgtcgg 83340 cttcgacctg accaacccta ccgctgacgt tatgggcaag accgaagaaa tcttcgtcca 83400 tatgcaagac aacagccaag acggtctgat ccgtggtgac ttcgttgccc tgtgctctcc 83460 tgagttcttc actgccctga ttaaccatcc gagcatcaaa gagttctaca aagcttacca 83520 agctagtcct caatactggc gtgaacgtct aaccgctcgc ggtctggacc ttcgcttccg 83580 tgagttctac ttcggaaaca ttcacttcat cgaataccgt ggcgttgacc cgtacggcaa 83640 ccgtctgatc ccggctggcg atgcttactt catcccaacc gacagcggtg acctgttcgc 83700 tcgttacttc ggcccgggca gcactttcga tgacctagga actctgggta aagaactgta 83760 cgctaccgag cgtatggctg aagaccgtcg ttcgatcctg atcgaaaccg agtccaactt 83820 catccacgtt ctgcgtcgtc cacagatgat cgttcgcggc actgtgaatg cgtaaagact 83880 tcagggaggc ttcggcctcc ctttcgtcgt aggagggtac caaaaaaatg gcttacactg 83940 gtgatccagc aaacaaccct atcgaccgtc tacgagagat tgtaggggac gtgtgggagc 84000 ctccgatgct ttccgacgaa acctatcaat gggtgttgga caagaacgaa ggcaacgaaa 84060 gacgagccgc acttgaactt atgcgtatga tgctcttccg cctgacaagg ggaatgagag 84120 aacgcacagg tgatatcgaa gtatatggtg ctgagtattt caacaactac ttgaaagctc 84180 ttcagctcat tctcaaagac ccgaatattg caatttctct ggccgtgcca tacgctggcg 84240 gtatctccaa atcggatatg ctggctaatg acctagaccc cgacaacgta acacgggaat 84300 tctacatcgg ttttgcaaga cgggagaagc tttacaacca gtgcaacccc ggtcctcaag 84360 accttagcat ggggtgtgat tatcttggca agcttcagtt ttaaaacaga tcgccgtcgc 84420 ctcacatcct tgattaagag ggtggaggct ctagacggaa caacggtaga agttggtttc 84480 ttccccgagg accgatatgg ttctgaaaat ggaaacctac cagttgcaca agttgcagct 84540 tacaacgaat tcggtactac tcgcaaccca acccggccat tcatggctcc aacctttgaa 84600 gaattcacat ctcaattcca ctacgcaaga ctaatgaagt ccacgttcga gaacgtccta 84660 cgcgatggaa ggcagacgaa tactcttctg aagaaattgg gtaaaatggt tgcagagcag 84720 atgcaagtta acattgacga ctatccgggc tctaacagtc cggcatgggc agcttacaaa 84780 ggatttaacg atcctctatt ccatactgga aagatgcttg agtctgtcaa gttccaaatc 84840 catcggaggc aataatgctc tatcctacct tctccatgac caacttcgta aagctagatt 84900 tgattagaag agggcagccc ggagacgacg gttttggaag acctacccct ccagttgaga 84960 cagtagtaac aatcacagct aacgttcaac ctatcgaaaa atcgacagac actcgtatcc 85020 ttccagaggc cgacagaagc aaggcttgct tcaaggtgta ctccagaggc gaagagattc 85080 gccagttaaa ggaaggcccg ggagggtgga gtgccgatag attcatgtgg gaaggagagt 85140 tgtatgaagt tatgaaagtc atcaactatt cgatgggaat cctaaaccat tacaaagcaa 85200 tttgtatgag agtagagagg aatagcacag catgatccac acagagctag aaaactccct 85260 ctatcttatg gtcaaagagt tgttccccga ctggcgtgta attcaagctt acacgaataa 85320 tcaggaaccg caaacccctt atctggctat cgacattaag aggctggatg aactgggaag 85380 ggaaaatgtc tccaatatga gcgatcccat tagtccttcg catggaacta ttcaagttca 85440 acaggacttc gcagccaaag tcgtattcga actgattggc aagtatggag agacagcaag 85500 tgtctctgac atggcaatgg cgattactcg ggcaatgcgt actccagcag gacacgccgc 85560 ccaaagaaag tttaatctat cccttttcaa actccctagc acaagacgag ttcctatgct 85620 aagagaaaca gatatgtaca tgttctatca agttacatgt gaatttggat tctctgtgat 85680 agaaaccaca actcaagagt ttgctgctgg ggctgatatt cacggcgttt attacgacgc 85740 tggtcgcccg ggtcacatta ttgagtccca catcgacata aacttcgaac actaatagga 85800 gacaggaatg actgttctta ctgatgtaat tgacattcag atcagccgtg agactgctgc 85860 tgtcgcacag acaaacttca acgttcctct gttcatcgct tctcacacaa acttctcgga 85920 acgtgccaga gtctacaaca gcctgaaagg tgtcgctgaa gacttcggag aatccgatcc 85980 aacatatctt gccgctgttc gctacttcgg tcaagctctc aagcctcgca gtctagttat 86040 cggacgcaga caagttcctt ctgctaccgt ctctgtcagt gttgttcagg aaggacaaag 86100 ctacgtcctt accgttaacg gactacctgt cagctatgtt agccagcaag acgacactgc 86160 caccctaatt gcaactggcc taaaagctgc atatgatgtt acccctgttg ttggcgttac 86220 cgtaactgac aacgaagacg gaactctgac tgtcgcttcg aacggagact ggagcctgaa 86280 ggtttcttct aacctgacta tggctgctgc tccttctact gaaggttggc cggctgctat 86340 cacagcagtt caaggagaaa acgacgaatg gtatgctctg agcattgaca gccacgccga 86400 tgatgatatc atggcagtag ctactcatat cgagggcacc aagaaagtgt ttatcggagc 86460 cactgctcag gctaacacca agacttccgc agagaatgac attgcttctc gtctggttgc 86520 tgccgggttc caacgtacgg ctctaattta ccatccaaac gctgacgctc aattccctga 86580 gtgtgcttgg gtaggatacc aactgcaaga gcaaccgggt agcaacacat ggacccataa 86640 agctctagct gccgtagatg cttaccgtct aaccccaacc gaatctacca acctgaagaa 86700 caagaacgtt accacgttcg agcgcgttgg tggtgtcaac cgtacattcg gtggcgctat 86760 ggccggtggt gaatggatcg acgtaatgat tttcgtggac tggctggaag cccgcatgac 86820 cgagcgtctg tggttccgta tggctaactc caagaaaatc ccttacgacg ccgttggtgc 86880 aacaattctg gaatcggaaa tcagagccca gcttaacgaa ggaattcgtg ttggtggtct 86940 ggctgaagct ccggctccta aagtcttcgt acctgatgtt ctatccatgt ctccgaacat 87000 gagagcacag cgtatctttg aaggcattga atttgaagcc cgtctggccg gtgccattca 87060 cttcgttcac attcgtggaa ctgtgaccgt ctaaggacgg tccttcccat aaggagatta 87120 ctaaatggct gttcaacgtc tagcgacatt ctctccggct gatgttacca ttgttattac 87180 tcaccctgca actggtgaga gcatggttct cggcggattc agcgaagaca gtatcgttaa 87240 cattgaaaga aacgctgaca cttacgtgat gtataccgga gccgacaaca catcgactcg 87300 cgtctacaac gcctctaagt ctgctaccct cactgttagc cttcaacaaa cttcgccttc 87360 gaacgacttc ctgactgctc tttacaacta cgacgacgcc cgtcgttcgt ctgagggatt 87420 gttcacaatc cacgttaaag acaactctgg tcgttccgac tacttcagtg atgacgccta 87480 tgtcggtgtt gttccgggtt ctaacttctc gaacagcatg cagacacgcg attgggttat 87540 tcatgcacac aacctgcaaa ctctaatcgg cggtaacgcc aagctgagcc cgggtgatgc 87600 ggatactctt cgtaacctag gtgtcacact agaccagcgc tggctgtaat atagcgctta 87660 tgccacatcg acggggagct gccttaacgg gtggctccct ttgttgtttc tggaggatag 87720 aaattgatta ccacctactc gccgcgtgac gtggttgtaa ctctcgctgg tatccattcc 87780 gtgacagggt acgcagaggg agagtttatc agaattgtaa aagatattaa gcctttcatc 87840 aagcacggtt cgatggatgg tgaaatcgca agggtctaca acaaagacca aggctggcga 87900 gtagagttga caatcatgca gtcctcgccg accaatgata tcctttcgat gctttacaac 87960 gtggacattg caacccgaat gggaaaattc ccactgatga ttaaggacac gaagggttct 88020 acaagcttcc tagctctgac agcatgggtg gaagacctac ctagggtatc tttctctgga 88080 caactggaga cccgcacttg gattctaggg tgctctgagg tcgccatgaa cattggcgga 88140 aacgtcgatc aaagtttggt cgagcaagct atcctgctgg gaagctctct tctgccagcc 88200 cttacgcaat tcggaggctt ctaatggcta acacggtatt gacatatagc ccgtctgatg 88260 ttaaaattgt cctttgtggg tatgctctca ctggtgtagt ttctttcgaa atgtcttggc 88320 tttcgagacc ctacacaatg gttcgaggaa tcagagggca ccacacccgg gtcttcaata 88380 gagacctttc tgcgcagatt agaatcgagg ttcttcagac ttcggtgtct aatgatgcat 88440 tcttctcgct agtagagcaa gaccgaagaa cacaatccgc ccgaatcacc ttgtctgtca 88500 aggataccca cggtagcacc atgatgagca cagacaacgc ttatgtcaat ggctacccta 88560 gcataacatt caccgatgga atcgagaaca gggtctggac tattgatgtt ctggactgga 88620 ccgatggcac ggtaggcgga aaccagcaag tcggcttcga cgtgtttgga actgttcaag 88680 gcgctcttag ctacctcaga taaataagga gtatttatgt tcggaaacca acgtactgtc 88740 atccacaatg ggacagaata cactatcaac cttctgccag caactcgcgg tatcagcgta 88800 ctgaagcagc taaccagctt gctgggtcca tcccttgcca agtatcaagc tgaccacgac 88860 ttctctggag ccatgaaaga actgttcgat aacatcgaca aggttcctgt tgagaatttg 88920 atccagaatc tgatgctgac agttttcaaa ggttcgatgg caatcaattt cgacaccgaa 88980 ttcgctggca agtatgacct gctgtacgca ctcacaaaag acgtgatcga gttcaacttc 89040 ggctcggttt tttctctaat cggtttcgca gaggcaccga cggtataaag accggggatg 89100 ggcagtccga gacttcagtc actactgatc gagttcagag tgatcggagg gttagggagg 89160 cccaccagaa gttctcgcag cattgggaga tttatgtggc tatcactcac cctctcaagc 89220 taacgacgta tggggaactg agtacagtcc tcactacaga agatttgtac aacatccttg 89280 aggttataga cgttcacgat actatcactc aagtggcaaa agaacacgca gaggctgata 89340 agaaatgatt acagaaagga ttgcccagct aactggggaa cttaaattta cagtcgattc 89400 ccggcctctc actgcttttg acaagaagct cgctggggtc gaagcccggc taagagaatt 89460 ctccaagctg acgaacaagc ggtttggagt taagctaact ctagatacaa aaactctgag 89520 agaggagctt gccaaggcag ccactcaaag ggtagtcttg aagaacatcg cggtagatgc 89580 tgccgctgtt cgtcttatct ctgagaagct tcaagaaaga ctgaatgcaa cgccgatcag 89640 gttgaagtct gttaggctag accttagcgg tatccgagat cagaaaaact tcgtaaagac 89700 ggctctcggc cagaccaagg tcgatctacc ggttgaactg ggcttggctc aggctagccg 89760 tacgctgtat gaatggaaga agcgcacaga gagtcgtttt aaaattcatc tgaatgcaga 89820 cattagccgc tctaaattgc tccagaatgc acgaaacaca ctaagggatg tgcagggtag 89880 gctaaacggt cttgctgtcg ctacgcctca aattaggctg tctgtagacc gtgcccatct 89940 tcgtagagag attcaagatg ttcttgagca aatcagacgc gaagtgagaa tccgcattga 90000 cctagagtct tccatccgag gaggtggtgc aggtggatcg agaggtactg ccggccatat 90060 ccgtcaaggt atgggaatgg ggattggtag cgagctagcc gggtggggac gcgggtttat 90120 tcccggcctt ggtggtgcgt tcgctattat gcagcttaac cgtgctaacc aagaactgca 90180 aggtcaacgt ctggccatgc aagctgtcgg tggtggagta cagggtggtc aagagctaca 90240 agccaccctc cgcgatatct ctcagcgtct cggtcttgac gatagagcaa taggtagctc 90300 ctatgttaag atgatggctg ccggacaagc atccaacttc gacaaaacac aggttgatgg 90360 catcttccaa tccatggctg aatatggacg agtgatgggt ctggatggcg aggccatgaa 90420 aggctccttc cgtgccgtag aacagatgat gggtaaagga caaatcatgt ccgaagaatt 90480 gaaaggtcag ttggccgaac gattccctgc ggctgtagcc ctgatggcta agtctcagga 90540 tatgtctatc gctgagctaa tgaaaaccat ggagaaaggg gagcttaaga gtgatgctct 90600 gatcccattc gccagaactc tagcggaaga agctcgtaaa ggtggcgctc tggacgcggc 90660 tatgcaaggt acagccgctc agcagggccg attccagttc ggatggaacc gcactatcga 90720 ggccttcgcg gctggaggat tcgaccgagg aatgagcgac ttcttcaaga ttgctgccca 90780 aggcatgaaa gaagcgcttc ctctggtaac tgcacttggt ggcgggttcg aagctcttat 90840 gaggcctgtc aacgctctgg tcggtattgg aggggagctt ggttcccagt gggagaacat 90900 tgccaagcag ttcaacatga ccggcacagg gctgactctt accacggctc aaaccctagc 90960 cttgctgacc cctatgggca ggttgatctc tgctattagc tggggtgcgt tggcactgga 91020 agacttcatt gtcttcttgg aaggcggtga ttcggtgttc ggggacttct tgaacaacaa 91080 cgtacaagct gccgagacat tcgaaaagct agccagtgaa tccagtgaac tgaagaacaa 91140 tctcgacggt atcttctctg ttgtcccggg gctagctgaa gcgctcaaag gtctagagtt 91200 caatgaaatg ctggtcagca cgatgagaga acttgctgcc atcatggagt tcttcaacag 91260 tgttgtagag agattcgcaa tagccggcaa gtacagggac gctaagattg ctgaagccgg 91320 aggagacaga agtactataa tgtcgaacat cgacacgatg tacgctatgt tcaatccgga 91380 agatgcaaaa gacaaggcca ccttcatcgg tgacaggcta gtagctcaga acattgacgc 91440 gatccagaca gagactcata cccgtgcaac ccagtccttg actccagacc agtttgggta 91500 tatgatgcaa cgtggtcaag ttagaaacga aatggagggt gccctcaaga agagtgccat 91560 tgacattagt ttcaacctca atgtttctgg tatcgatgct cagggtaacg tcatgacaac 91620 tgaagcgcaa gagcgagtac gagagatcgt tagtaacgtt cttgaggaag aaatctccag 91680 agcttcggca agttataagg aatcccaatg acaattgcta tcaaaagaga gaacggagac 91740 ctaatctggt tcgacgctgt tacagagttc ggaagacagt accgtggctc tgtgagttcc 91800 aacccaatcg aaacgggagg aaaaatcaca gaccacatta ctacagaaaa cccagtcttc 91860 actcttacag ccgtcgtatc agacgcagac ttcaacttga acaggcccgt tatcaacgac 91920 aacgaggccc agacatacaa gatcaacaac aaagagttcg tgaatacgca gccggtcagt 91980 gtgccggctg ttatcacaac ttccagattt gatccgagcc gaatcttccc ggaagttatt 92040 actcagttta ttcctcctga gattccttct gcaactgtcc tccctcaaaa gggtgataaa 92100 gtcgcttatg atattgagcg ccaactgatc gacatgcagc gtaatgctga ggtcttcagt 92160 ttgctggact tccgagacgg tatcatctgg gatcaaatcg aaagatgcat cttcaccgac 92220 ttgtctttca ctgaaaacgc cgagacaggt agcagccttc aacctcgtat gacaatcgag 92280 gctgtgacat tcacagatac tcgttatgtc gaggtgaggg ttaacaaggg tagaaagacc 92340 gctaagaaag aaaagagaga caccaaagaa ggtgataccg gggctagcaa tgctaccagc 92400 caagactctc ctacattcaa gcgtagtcaa atgaaagagg ctcagattag aactcaggtt 92460 gcgaggtaga ctaaatgagc acgacttata tcgacacact tcctctttac caagatcgga 92520 agtacaggta cgcagtagct atcgagggaa tctcaagagt ccttcaattt tactggaata 92580 gccgctctag gcagtggcac atggatatat tcgacgagga gcttactccg atcctgacag 92640 gactggcggt tgttcctcag tacccgatca tggcagatta cgccatgcaa catataggtt 92700 tcaatggcta cttcctgctg atgcctgtca ac 92732

Claims (9)

  1. 이미페넴 내성 녹농균(Imipenem Resistant Pseudomonas aeruginosa, IRPA)에 특이적인 증식 억제 및 사멸능을 갖는 박테리오파지 PA14 (수탁번호 KFCC11738P)로서,
    상기 박테리오파지는 서열번호 1로 표시되는 염기서열로 이루어지고, 전체 게놈 크기가 92,327 bp인 것을 특징으로 하는, 박테리오파지 PA14.
  2. 삭제
  3. 삭제
  4. 제1항의 박테리오파지 PA14를 포함하는, 항생용 조성물.
  5. 제1항의 박테리오파지 PA14를 포함하는, 사료 첨가용 조성물.
  6. 제5항의 사료 첨가용 조성물을 포함하는, 사료.
  7. 제1항의 박테리오파지 PA14를 포함하는, 소독제.
  8. 제1항의 박테리오파지 PA14를 포함하는, 세척제.
  9. 제1항의 박테리오파지 PA14를 인간을 제외한 개체에 투여하는 단계를 포함하는, 이미페넴 내성 녹농균에 의한 감염성 질병의 예방 또는 치료 방법.
KR1020170180963A 2017-12-27 2017-12-27 신규한 이미페넴 내성 녹농균 특이 박테리오파지 pa14 및 이를 포함하는 항균 조성물 KR102037387B1 (ko)

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Citations (1)

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Publication number Priority date Publication date Assignee Title
EP2248890A1 (en) 2009-04-30 2010-11-10 Institut Pasteur Bacteriophages specific to PAK and CHA strains of Pseudomonas aeruginosa and their applications

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KR101789877B1 (ko) * 2015-10-01 2017-10-26 연세대학교 산학협력단 항생제 내성을 갖는 슈도모나스 균속을 용균하는 박테리오파지

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EP2248890A1 (en) 2009-04-30 2010-11-10 Institut Pasteur Bacteriophages specific to PAK and CHA strains of Pseudomonas aeruginosa and their applications

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Pseudomonas phage K5, complete genome, GenBank: KU497559.1, 2016.02.10.

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