KR20210000659A - 신규한 살모넬라균 특이 박테리오파지 ss1 및 이를 포함하는 항균 조성물 - Google Patents
신규한 살모넬라균 특이 박테리오파지 ss1 및 이를 포함하는 항균 조성물 Download PDFInfo
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- bacteriophage
- salmonella
- present
- bacteria
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Abstract
본 발명은 살모넬라균, 특히 살모넬라 세텐베르그(Salmonella Senftenberg)에 특이적인 사멸능을 갖는 신규 박테리오파지 SS1, 상기 박테리오파지를 포함하는 항생용 조성물, 사료 첨가용 조성물, 사료, 소독제 또는 세척제 및 상기 박테리오파지를 개체에 투여하는 단계를 포함하는 살모넬라균에 의한 감염성 질병의 예방 또는 치료 방법에 관한 것이다. 본 발명의 박테리오파지 SS1을 이용한 살모넬라균에 의한 감염성 질병의 예방 또는 치료 방법은 기존의 항생제 등의 화학물질에 비해 살모넬라균에 대한 특이성이 매우 높고, 상기 박테리오파지 SS1은 살모넬라균에 감염하여 균 내에서 증식함으로써 용균 활성이 우수하고 물리화학적 자극에 강하다는 장점을 가지고 있다. 또한 본 발명의 박테리오파지 SS1은 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 SS1은 살모넬라균, 특히 살모넬라 세텐베르그에 의한 감염성 질병의 예방 또는 치료, 항생용 조성물, 사료 첨가용 조성물, 사료, 소독제, 또는 세척제 분야에서 다양하게 사용될 수 있다.
Description
본 발명은 살모넬라균, 특히 살모넬라 세텐베르그(Salmonella Senftenberg)에 특이적인 사멸능을 갖는 신규 박테리오파지 SS1, 상기 박테리오파지를 포함하는 항생용 조성물, 사료 첨가용 조성물, 사료, 소독제 또는 세척제 및 상기 박테리오파지를 개체에 투여하는 단계를 포함하는 살모넬라균에 의한 감염성 질병의 예방 또는 치료 방법에 관한 것이다.
살모넬라(Salmonella)는 장내세균과에 속하는 그람음성의 통성혐기성 세균으로, 아포를 형성하지 않는 간균이다. 살모넬라균은 사람뿐만 아니라 돼지, 소, 닭 등을 비롯한 다양한 가축에 감염되어 질병을 유발하는데, 사람에게 감염되어 식중독을 유발하고 동물에게 있어서는 다양한 살모넬라증(Salmonellosis)을 유발하는 병원성 미생물이다.
살모넬라 세텐베르그(Salmonella Senftenberg)는 1928년 독일의 세텐베르그 병원에서 급성장염이 발생한 어린아이의 분변에서 발견되어 병원의 이름을 따라 S. Senftenberg로 명명되었다. USDA 국립 수의학 연구소에서 2016년에 동물 및 환경에서 분리된 살모넬라의 혈청형을 분석한 결과, 소, 돼지, 닭, 말 등의 비임상 샘플에서 분리된 살모넬라의 혈청형 중 S. Senftenberg가 전체 혈청형의 13%를 차지하여 가장 높은 분리율을 보였다. 그 중에서도 양계에서 가장 높은 분리율을 보였는데 3천여개의 샘플에서 분리된 살모넬라의 15%가 S. Senftenberg인 것으로 확인되었다. 또한 칠면조에서 분리된 살모넬라 혈청형 중 21%의 분리율을 보여 S. Hadar에 이어 두번째로 높은 분리율을 나타냈다. 또한 2001년부터 2010년까지 국내의 양계농장 및 도계장에서 분리한 살모넬라균의 혈청형을 동정한 결과 S. Enteritidis와 S. Gallinarum에 이어 9.2%를 차지하여 세 번째로 높은 분리율을 보였다. S. Senftenberg는 다른 살모넬라 혈청형에 비해 열에 대한 내성이 강하며 주요 혈청형 중 하나인 S. Typhimurium보다 약 30배 가량의 내열성을 가지고 있는 것으로 알려져 있다. 또한 건조, 산, 자외선 등에도 저항성이 높아 계란과 닭고기를 포함한 가금류 제품의 세척 및 소독 과정에서 살아남을 수 있다. 농장에서부터의 세균 제어가 필요하나 화학적 살균제나 항생제를 사용하지 않은 친환경 제품의 선호도가 증가함에 따라 살모넬라 오염에 의한 식중독 사고가 증가할 확률이 높아지고 있는 상황이다.
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 박테리오파지(bacteriophage)의 활용이 크게 주목을 받고 있다. 특히 2000년 이후에 항생제 내성균의 증가로 인하여 기존 항생제의 한계성이 나타나고, 기존 항생제의 대체 물질로의 개발 가능성이 부각되면서 다시 박테리오파지가 항-박테리아제로 주목을 받고 있다.
이에 본 발명자들은 살모넬라균에 특이적인 용균활성을 갖는 박테리오파지를 분리하고 분리된 박테리오파지의 형태적 및 유전적 특성을 분석하여 상기 박테리오파지가 살모넬라균, 특히 살모넬라 세텐베르그를 선택적으로 사멸시킬 수 있음을 확인함으로써 본 발명을 완성하였다.
본 발명의 목적은 살모넬라 세텐베르그(Salmonella Senftenberg)에 특이적인 사멸능을 갖는, 서열번호 1로 표시되는 염기서열로 이루어진 박테리오파지 SS1을 제공하는 것이다.
본 발명의 또 다른 목적은 상기 박테리오파지 SS1을 포함하는, 항생용 조성물, 사료 첨가용 조성물, 사료, 소독제 또는 세척제를 제공하는 것이다.
본 발명의 또 다른 목적은 상기 박테리오파지 SS1을 개체에 투여하는 단계를 포함하는, 살모넬라 세텐베르그에 의한 감염성 질병의 예방 또는 치료 방법을 제공하는 것이다.
상기 목적을 달성하기 위하여, 본 발명은 살모넬라 세텐베르그(Salmonella Senftenberg)에 특이적인 사멸능을 갖는, 서열번호 1로 표시되는 염기서열로 이루어진 박테리오파지 SS1을 제공한다.
또한, 본 발명은 상기 박테리오파지 SS1을 포함하는, 항생용 조성물을 제공한다.
또한, 본 발명은 상기 박테리오파지 SS1을 포함하는, 사료 첨가용 조성물을 제공한다.
또한, 본 발명은 상기 사료 첨가용 조성물을 포함하는, 사료를 제공한다.
또한, 본 발명은 상기 박테리오파지 SS1을 포함하는, 소독제를 제공한다.
또한, 본 발명은 상기 박테리오파지 SS1을 포함하는, 세척제를 제공한다.
또한, 본 발명은 상기 박테리오파지 SS1을 개체에 투여하는 단계를 포함하는, 살모넬라 세텐베르그에 의한 감염성 질병의 예방 또는 치료 방법을 제공한다.
본 발명의 박테리오파지 SS1은 기존의 항생제 등의 화학물질에 비해 살모넬라균에 대한 특이성이 매우 높고, 상기 박테리오파지 SS1은 살모넬라균에 감염하여 균 내에서 증식함으로써 용균 활성이 우수하고 물리화학적 자극에 강하다는 장점을 가지고 있다. 또한 본 발명의 박테리오파지 SS1은 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 SS1은 살모넬라균, 특히 살모넬라 세텐베르그에 의한 감염성 질병의 예방 또는 치료, 항생용 조성물, 사료 첨가용 조성물, 사료, 소독제, 또는 세척제 분야에서 다양하게 사용될 수 있다.
도 1은 전자 현미경을 통해 박테리오파지 SS1의 형태학적 특성을 확인한 결과를 나타낸 도이다.
도 2는 박테리오파지 SS1의 세균 사멸 능력을 평가한 결과를 나타낸 도이다.
도 3은 박테리오파지 SS1의 pH 안정성을 확인한 결과를 나타낸 도이다.
도 4는 박테리오파지 SS1의 열 안정성을 확인한 결과를 나타낸 도이다.
도 2는 박테리오파지 SS1의 세균 사멸 능력을 평가한 결과를 나타낸 도이다.
도 3은 박테리오파지 SS1의 pH 안정성을 확인한 결과를 나타낸 도이다.
도 4는 박테리오파지 SS1의 열 안정성을 확인한 결과를 나타낸 도이다.
이하, 본 발명에 대해 상세히 설명한다.
본 발명은 살모넬라 세텐베르그(Salmonella Senftenberg)에 특이적인 사멸능을 갖는, 서열번호 1로 표시되는 염기서열로 이루어진 박테리오파지 SS1을 제공한다.
본 발명에서, 용어 박테리오파지(bacteriophage)는 특정 세균에 감염하여 당해 세균의 성장을 억제하고 저해하는 세균 특이적 바이러스로, 단일 혹은 이중 사슬의 DNA 또는 RNA를 유전 물질로 포함하는 바이러스를 의미한다.
본 발명에서, 상기 살모넬라 세텐베르그는 다제내성(multidrug resistance) 살모넬라 세텐베르그일 수 있으며, 예를 들어, 앰피실린, 테트라사이클린, 날리딕스산, 아목시실린 또는 시프로플록사신 등의 항생제에 대한 내성을 가진 살모넬라 세텐베르그를 포함하나, 이에 제한되는 것은 아니다.
본 발명의 박테리오파지 SS1은 살모넬라 세텐베르그에 대해 용균활성이 탁월하다. 상기 박테리오파지 SS1은 310-320 nm의 크기로, 정이십면체의 머리를 가지며 수축성의 꼬리를 가지는 형태인 사이포비리대(Siphoviridae)에 속한다.
또한 상기 박테리오파지 SS1은 열 및 pH에 대한 안정성이 우수한 특성을 가지고 있다.
박테리오파지 SS1은 전체 유전자의 크기는 77,888 bp이며, GC 함량은 50.1%, 전체 유전자의 수는 123개이다. 또한 상기 박테리오파지 SS1의 전체 유전자 서열은 서열번호 1로 표시될 수 있다.
또한 상기 박테리오파지 SS1은 서열번호 1로 표시되는 염기서열을 전체 유전자의 전체 또는 일부로서 포함할 수 있다. 또한, 본 발명의 박테리오파지 SS1은 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 살모넬라균 특이적 용균활성, 내산성, 내염기성 및 내열성은 본 발명의 박테리오파지 SS1을 살모넬라균에 의한 감염성 질병의 예방 및 치료용 조성물, 및 상기 박테리오파지 SS1을 유효성분으로 포함하는 다양한 제품에 적용함에 있어, 다양한 온도 및 pH 범위의 적용이 가능하게 한다.
본 발명의 박테리오파지 SS1은 양계장 시료로부터 분리한 박테리오파지로서, 본 발명자는 박테리오파지 SS1로 명명하고 2019년 4월 12일에 한국미생물보존센터 (Korean Culture Center of Microorganisms, 서울, 한국)에 기탁하여, 수탁번호 KFCC11829P를 부여받았다.
또한, 본 발명은 상기 박테리오파지 SS1을 포함하는, 항생용 조성물을 제공한다.
본 발명에서, 용어 항생용 조성물은 약제 형태로 동물에게 제공되어 균을 사멸시킬 수 있는 제제를 의미하며, 방부제, 살균제, 항생제 및 항균제를 총칭하는 것이다.
본 발명의 박테리오파지 SS1은 기존 항생제에 비하여 살모넬라균에 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 SS1을 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 SS1을 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 분해 효소 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 SS1을 포함하는 사료에는 식물성으로는 곡물류, 근과류, 식품가공 부산물류, 조류, 섬유질류, 제약 부산물류, 유지류, 전분류, 박류, 곡물부산물류 등이 있으며, 동물성으로는 단백질류, 무기물류, 유지류, 광물성류, 단세포 단백질, 동물성 플랑크톤류, 남은 음식물 등이 있으며 이에 제한되는 것은 아니다.
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 SS1을 포함하는, 음용수 첨가제를 제공한다.
본 발명의 음용수 첨가제는 상기 박테리오파지 SS1 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 살모넬라균의 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 SS1을 포함하는, 소독제를 제공한다.
살모넬라균, 예컨대 살모넬라 세텐베르그에 특이적 사멸능을 갖는 본 발명의 박테리오파지 SS1을 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 SS1을 포함하는, 세척제를 제공한다.
본 발명의 박테리오파지 SS1은 살모넬라균, 예컨대 살모넬라 세텐베르그에 특이적 사멸능을 가지므로, 상기 살모넬라균에 노출되었거나 노출될 가능성이 있는 가축의 피부 표면 또는 신체 각 부위 등을 세척하는 용도로도 사용될 수 있다.
또한, 본 발명은 상기 박테리오파지 SS1을 포함하는, 살모넬라 세텐베르그에 의한 감염성 질병의 예방 또는 치료용 약학적 조성물을 제공한다.
본 발명의 박테리오파지 SS1은 살모넬라균에 특이적인 사멸능을 가지므로, 살모넬라 세텐베르그에 의한 감염성 질병의 예방 또는 치료용 약학적 조성물에 사용될 수 있다.
본 발명에서, 살모넬라균, 특히 살모넬라 세텐베르그에 의한 감염성 질병은 유행성 또는 급성으로 발병하는 전염성 질환을 통칭하는 개념으로, 살모넬라증 외에 식중독, 장염, 폐렴 및 패혈증 등을 포함하나, 이에 제한되는 것은 아니다.
상기 살모넬라증은 살모넬라균 감염에 의해 발열, 두통, 설사, 구토 등을 수반하는 증상을 총칭하는 것으로, 살모넬라증은 장티푸스와 같은 증세를 나타내는 패혈증형과 식중독 증세를 나타내는 급성위장염형으로 대별되며, 장염, 식중독, 급성 균혈증 등이 포함된다.
본 발명의 약학적 조성물은 1 × 103 내지 1 × 1010 PFU/mL의 박테리오파지를 포함하며, 바람직하게는 1 × 106 내지 1 × 109 PFU/mL의 박테리오파지를 포함한다. 본 발명에 사용된 용어, PFU(plaque forming unit)는 박테리오파지가 플라크를 형성하는 것을 수치화한 단위이다.
본 발명의 용어 예방이란 조성물의 투여로 질병을 억제시키거나 발병을 지연시키는 모든 행위를 의미한다.
본 발명의 용어 치료란 조성물의 투여로 상기 질병의 증세가 호전되거나 상기 질병의 억제 또는 경감 및 이롭게 변경되는 모든 행위를 의미한다.
본 발명의 약학적 조성물은 약학적으로 허용 가능한 담체를 추가로 포함할 수 있다.
본 발명에서, 용어 약학적으로 허용 가능한 담체란 생물체를 자극하지 않고 투여 화합물의 생물학적 활성 및 특성을 저해하지 않는 담체 또는 희석제를 의미한다. 액상 용액으로 제제화되는 조성물에 있어서 허용되는 약제학적 담체로는, 멸균 및 생체에 적합한 것으로서, 식염수, 멸균수, 링거액, 완충 식염수, 알부민 주사용액, 덱스트로오스 용액, 말토 덱스트린 용액, 글리세롤, 에탄올 및 이들 성분 중 1성분 이상을 혼합하여 사용할 수 있으며, 필요에 따라 항산화제, 완충액, 정균제 등 다른 통상의 첨가제를 첨가할 수 있다. 또한 희석제, 분산제, 계면활성제, 결합제 및 윤활제를 부가적으로 첨가하여 수용액, 현탁액, 유탁액 등과 같은 주사용 제형, 환약, 캡슐, 과립 또는 정제로 제제화할 수 있다.
본 발명의 약학적 조성물은 경구 투여 외에 비경구 투여, 비강분무, 질환 부위에의 도포 또는 분무하는 방법으로 이용할 수 있으며, 비경구 투여의 경우 정맥 내 투여, 복강 내 투여, 근육 내 투여, 피하 투여 또는 국부 투여를 이용하여 투여할 수도 있다.
본 발명의 약학적 조성물을 유효성분으로 포함하는 경구 투여용 제형으로는, 예를 들어 정제, 트로키제, 로렌지, 수용성 또는 유성현탁액, 조제분말 또는 과립, 에멀젼, 하드 또는 소프트 캡슐, 시럽 또는 엘릭시르제로 제제화할 수 있다. 정제 및 캡슐 등의 제형으로 제제화하기 위해, 락토오스, 사카로오스, 솔비톨, 만니톨, 전분, 아밀로펙틴, 셀룰로오스 또는 젤라틴과 같은 결합제, 디칼슘 포스페이트와 같은 부형제, 옥수수 전분 또는 고구마 전분과 같은 붕괴제, 스테아르산 마그네슘, 스테아르산 칼슘, 스테아릴푸마르산 나트륨 또는 폴리에틸렌글리콜 왁스와 같은 윤활유를 포함할 수 있으며, 캡슐 제형의 경우 상기 언급한 물질 외에도 지방유와 같은 액체 담체를 더 함유할 수 있다.
본 발명의 약학적 조성물을 유효성분으로 포함하는 비경구 투여용 제형으로는, 피하주사, 정맥주사 또는 근육 내 주사 등의 주사용 형태, 좌제 주입방식 또는 호흡기를 통하여 흡입이 가능하도록 하는 에어로졸제 등 스프레이용으로 제제화할 수 있다. 주사용 제형으로 제제화하기 위해서는 본 발명의 조성물을 안정제 또는 완충제와 함께 물에서 혼합하여 용액 또는 현탁액으로 제조하고, 이를 앰플 또는 바이알의 단위 투여용으로 제제화할 수 있다. 에어로졸제 등의 스프레이용으로 제형화하는 경우, 수분산된 농축물 또는 습윤 분말이 분산되도록 추진제 등이 첨가제와 함께 배합될 수 있다.
본 발명의 약학적 조성물의 적합한 도포, 분무 및 투여량은 제제화 방법, 투여 방식, 대상이 되는 동물 및 환자의 연령, 체중, 성, 질병 증상의 정도, 음식, 투여시간, 투여 경로, 배설 속도 및 반응 감응성과 같은 요인들에 의해 다양하며, 보통으로 숙련된 의사나 수의사는 목적하는 치료에 효과적인 투여량을 용이하게 결정 및 처방할 수 있다.
또한, 본 발명은 상기 박테리오파지 SS1을 개체에 투여하는 단계를 포함하는, 살모넬라 세텐베르그에 의한 감염성 질병의 예방 또는 치료 방법을 제공한다.
본 발명의 방법은 살모넬라 세텐베르그에 의한 감염성 질병, 예컨대 유행성 또는 급성으로 발병하는 전염성 질환으로, 살모넬라증 외에 식중독, 장염, 폐렴 또는 패혈증이 발생한 개체 또는 발생 위험이 있는 개체에 박테리오파지 SS1을 투여하는 단계를 포함한다.
본 발명에서, 용어 개체는 살모넬라 세텐베르그에 의한 감염성 질병이 발병될 수 있는 모든 개체를 의미하는 것으로 인간을 포함한 포유동물, 가축류 또는 가금류를 포함하나, 이에 제한되는 것은 아니다.
상기 용어 가축류는 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 가금류는 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 SS1 또는 조성물은 약학적 제제의 형태로 동물에게 투여되거나, 가축의 사료 또는 음용수에 혼합하여 이를 섭식시키는 방법을 통해 투여될 수 있다.
본 발명의 방법에서 상기 박테리오파지 SS1 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 SS1의 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 기술분야에서 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 단일 박테리오파지의 분리
살모넬라 세텐베르그에 특이적인 박테리오파지를 스크리닝 및 분리하기 위해서 용균반 분석을 수행하였다. 시료는 박테리오파지가 존재할 것으로 예상되는 양계농장 부근의 하수로부터 시료를 채취하였으며, 박테리오파지 분리에 사용된 살모넬라 세텐베르그는 (주)옵티팜에서 채취한 야외 시료로부터 분리 동정된 것을 사용하였다.
구체적으로, 채취한 시료를 균질화 한 후 살모넬라 세텐베르그와 함께 35℃에서 24시간 동안 100 rpm으로 진탕배양 하였다. 상기 배양액을 3,000 rpm으로 25분간 원심분리한 후, 상등액을 공극(pore) 크기가 0.45 μm인 필터를 이용하여 여과하여 시료 여과액을 얻었다.
전배양된 살모넬라 세텐베르그 150 μL를 취해서 멸균된 튜브에 넣고 3 mL의 LB 탑 아가(top agar) (LB 배지(트립톤 10 g/L, 효모 추출물(yeast extract) 5 g/L, NaCl 10 g/L) + 0.6% 아가)를 첨가하여 잘 혼합한 후 미리 만들어 둔 2% LB 아가 플레이트에 중층하였다. 이를 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(살모넬라 세텐베르그) 배양액 150 μL에 혼합한 후 0.6% LB 탑 아가 3 mL을 첨가하여 잘 혼합한 뒤, 미리 만들어 둔 2% LB 아가 플레이트에 중층하여 방치한 후 35℃에서 15시간 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 200 μL를 0.6% LB 탑 아가와 세균 배양액 300 μL와 혼합한 뒤 150 mm 지름의 LB 플레이트에 분주하여 중층한 후 완전히 용균이 일어날 때까지 35℃에서 배양하였다. 배양이 종료된 후, LB 플레이트에 15 mL의 SM 완충액을 가하고 실온에서 4시간 동안 천천히 교반하면서 박테리오파지 용액을 회수한 후 3,000 rpm으로 20분간 원심분리하여 상등액만 취하고 이를 0.45 μm 필터로 여과하여 최종 박테리오파지 용액을 회수하였다.
1.2 박테리오파지의 대량 배양 및 정제
상기 실시예 1.1에서 확인한 살모넬라 세텐베르그 특이적 박테리오파지를 대량 배양하기 위하여, 1.1에서 회수한 최종 박테리오파지 배양액을 1.0x109 PFU/mL로 희석한 후 전배양된 살모넬라 세텐베르그 1.0x108 CFU/mL과 혼합하고 MOI(Multiplicity of infection)를 0.1이 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 SS1(Bacteriophage SS1)"로 명명하고, 2019년 4월 12일에 한국미생물보존센터 (Korean Culture Center of Microorganisms, 서울, 한국)에 기탁하고, 수탁번호 KFCC118129P를 부여받았다.
실시예 2: 박테리오파지 SS1의 전체 유전자 분석
박테리오파지 SS1의 전체 유전자를 분석하기 위해, 박테리오파지 SS1 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 μL이 되도록 TE 완충액 (Tris-EDTA, pH8.0)에 용해시킨 후 DNA 농도를 측정하였다. 전체 유전자 분석을 위해 PacBioRSII를 이용하여 유전자 시퀀싱을 시행하였다(마크로젠, 한국).
시퀀싱 결과로 얻은 박테리오파지 SS1의 전체 유전자의 크기는 77,888 bp이며, GC함량은 50.1%, 전체 유전자의 수는 123개임을 확인하였다. 분석한 박테리오파지 SS1의 전체 유전자 서열을 서열번호 1로 나타내었다.
실시예 3: 박테리오파지 SS1의 형태학적 특성
박테리오파지 SS1의 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 1에 나타내었다.
도 1에 나타낸 바와 같이, 박테리오파지 SS1은 310-320 nm의 크기로, 정이십면체의 머리를 가지며 수축성의 꼬리를 가지는 형태인 사이포비리대(Siphoviridae)에 속함을 확인하였다.
실시예 4: 박테리오파지 SS1의 다양한 세균에 대한 감염성 조사
박테리오파지 SS1의 다양한 세균에 대한 감염성을 조사하였다.
우선, 박테리오파지 SS1의 살모넬라 세텐베르그에 대한 용균 활성을 확인하기 위하여, ㈜옵티팜에서 분리하여 보유하고 있는 살모넬라 세텐베르그 균주를 대상으로 소프트 아가 오버레이법을 수행하였다. 그 결과를 표 1에 나타내었다.
상기 표 1에 나타낸 바와 같이, 본 발명의 박테리오파지 SS1은 살모넬라 세텐베르그에 대해 높은 감수성을 보임을 확인하였다.
또한, 박테리오파지 SS1이 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.
(+: 용균활성 있음, -; 용균활성 없음)
표 2에 나타낸 바와 같이, 본 발명의 박테리오파지 SS1은 살모넬라 세텐베르그에 대한 용균활성을 가지는 것을 확인하였다. 또한 박테리오파지 SS1은 살모넬라 세텐베르그가 아닌 다른 살모넬라균과; Bacillus cereus, Pseudomonas aeruginosa, Listeria monocytogenes 등 살모넬라균이 아닌 다른 속의 세균;에 대해서는 용균활성이 없는 것을 확인하였다.
따라서, 본 발명의 박테리오파지 SS1은 살모넬라 세텐베르그에 특이적으로 용균활성을 나타내는 박테리오파지임을 확인하였다.
실시예 5: 박테리오파지 SS1의 세균 사멸 능력 조사
박테리오파지 SS1의 세균 사멸 능력을 조사하였다.
박테리오파지 SS1의 살모넬라 세텐베르그에 대한 사멸 능력을 분석하기 위하여, 600 nm에서 흡광도가 약 0.3인 세균 배양액을 10 mL 준비하였다. 세균 배양액에 농도가 1.0x108 PFU/mL인 박테리오파지액을 1 mL 넣어 MOI 1로 접종한 실험군과 박테리오파지액을 넣지 않은 시료를 대조군으로 하여 실험을 진행하였다. 3시간 동안 배양하며 1시간 단위로 흡광도 600 nm에서 세균의 배양 상태를 관찰하였다. 박테리오파지 SS1의 세균 사멸 능력은 표 3 및 도 2에 나타내었다.
(단위 : OD600nm)
표 3 및 도 2에 나타낸 바와 같이, 박테리오파지 SS1을 첨가하지 않은 대조군의 경우 3시간 후 600 nm에서 흡광도가 1.16로 나타나 세균이 증식한 것을 확인하였다. 반면, 박테리오파지 SS1을 첨가한 실험군의 경우 3 시간 경과했을 때 600 nm에서 흡광도가 0.3으로 배양 시작단계와 비슷한 흡광도를 보여 세균이 증식하지 않은 것을 알 수 있다.
실시예 6: 박테리오파지 SS1의 pH 안정성 조사
박테리오파지 SS1의 pH에 대한 안정성을 확인하기 위하여, 다양한 pH 범위(pH 2, 3, 4, 5, 6, 7, 8, 9, 10, 11)에서 박테리오파지의 수를 측정하였다. 소듐 아세테이트 완충액, 소듐 포스페이트 완충액, Tris-HCl을 이용하여 각각의 pH에 맞게 조제한 후 990 μL로 분주하여 준비하였다. 박테리오파지 SS1 배양액을 3.0x109 PFU/mL가 되도록 준비한 다음 배양액을 10 μL씩 취하여 pH에 맞게 조제한 각각의 완충액에 첨가하여 2시간 동안 상온에서 방치하였다. 방치 후 각 반응액을 단계 희석하여 소프트 아가 오버레이법에 의해 타이터(titer) 측정을 수행한 결과를 도 3에 나타내었다.
도 3에 나타낸 바와 같이, 본 발명의 박테리오파지 SS1은 pH 4-10의 범위에서 2시간 동안 안정한 것을 확인하였다. 이를 통해 박테리오파지 SS1은 pH 안정성이 우수한 박테리오파지임을 알 수 있다.
실시예 7: 박테리오파지 SS1의 열 안정성 조사
박테리오파지 SS1의 열 안정성을 확인하기 위하여, 40℃, 50℃ 및 60℃ 등 다양한 온도 범위에서 일정 시간 방치 후 박테리오파지의 수를 측정하였다. 보다 구체적으로, 박테리오파지 SS1 배양액을 5.0x108 PFU/mL가 되도록 희석한 후 배양액 5 mL을 멸균된 튜브에 분주하고 30분, 1시간 및 2시간 동안 각 온도에서 방치하였다. 방치 후 각 반응액을 단계희석하여 소프트 아가 오버레이법에 의한 타이터 측정을 수행한 결과를 도 4에 나타내었다.
도 4에 나타낸 바와 같이, 본 발명의 박테리오파지 SS1은 40-60℃의 범위에서 안정한 것을 확인하였다.
상기 실험으로부터 박테리오파지 SS1은 살모넬라균에 대한 특이성이 매우 높고, 살모넬라균에 감염하여 균 내에서 증식함으로써 용균 활성이 우수하고 물리화학적 자극에 강하다는 장점을 가지고 있음을 확인하였다. 또한 본 발명의 박테리오파지 SS1은 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 SS1은 살모넬라 스텐베르그에 의한 감염성 질병의 예방 또는 치료, 항생용 조성물, 사료 첨가용 조성물, 사료, 소독제, 또는 세척제 분야에서 다양하게 사용될 수 있다.
이상, 본 발명내용의 특정한 부분을 상세히 기술하였는바, 당업계의 통상의 지식을 가진 자에게 있어서, 이러한 구체적인 기술은 단지 바람직한 실시양태일 뿐이며, 이에 의해 본 발명의 범위가 제한되는 것이 아닌 점은 명백할 것이다. 따라서 본 발명의 실질적인 범위는 첨부된 청구항들과 그것들의 등가물에 의해 정의된다고 할 것이다.
<110> Optipharm.CO.,LTD
<120> Novel Salmonella specific bacteriophage SS1 and antibacterial
composition comprising the same
<130> 1-83P-1
<150> KR 10-2019-0075633
<151> 2019-06-25
<160> 1
<170> KoPatentIn 3.0
<210> 1
<211> 77888
<212> DNA
<213> Unknown
<220>
<223> Salmonella Senftenberg phage SS1
<400> 1
tgcgaacgat atggacgggc gcctcgctgg cttccacatg atctcgtata acactcatga 60
cgaaccgcct ggcctgataa cccggaacaa cgctgattcg gagtatctga ccaaagacga 120
aataaagctg gcaaatgacg cgctggcgaa agtatcgaaa atggttcggg caacgatgcc 180
gacgccgcga ccgcaaacac cgatggagga cgcctggtga aaagtaacgc tttctttgac 240
actgcggcgc cactctacgg cgtcaataag ctggcggtga atatcatcaa gccggcgcac 300
attgacgaca cgttcgccaa agccaataag caattagggt tgagcgaaag ccacgaccca 360
atcccctggt gtcgcccgcc agaagcgtcg ctgatcaacc cggcgttcgt cgatatgaca 420
ggcgttcagt ctggtcggtt gaaggtgctt gggttggagg cggcgccgcg cagaactaaa 480
ccgccacgtt gggtctgccg ttgtgtctgc ggaacttatg ttctgcgccg cacaaaggcg 540
ttaaagccag cgcatcattg catcgaatcg ttcgcctgca ctgactgcat taatctggcc 600
cgtatcaaac gaaatgaata tgttcgccgc accggtaaag aagccgacgc ggaagatttc 660
ttataaggag aatgcaatga gttctacaca cggccacgtt ctgccaaacg aagcataccc 720
gacgccagaa acgcacgttc gcaccatgct ggacaaactg gtgctccgca gcactgacca 780
gttcctcgaa ccgtgtcgcg gcgccgcgca ggctatctac aagcaggtgg atctcccgga 840
ggggcagaag cattgggctg aactgaccga agggcgcgac tacctggcga ccgactttgg 900
cgaaaagacg atggatgtga tcatcacgaa cccgccattc tccctgacct gcgagttcat 960
ggaaaagtcg ttccgcgaat tgaaggacga cggcaccctg atctacctcc agcgcgtcaa 1020
cttcctgggt gcggtgaagc gtgtggattt ttggcagaaa gtgggctacc cggagaagtt 1080
tccggtgctg atcccgcgcc cacgtttcgt cactgagaaa agcgactcga ccgagtatgc 1140
ctggttcatc tatgaccgcg gcaaccgctt cccgacgctg ccgcaaggta tcagtgcgct 1200
ggtcaacccg tatatctaat ggcgctgtta tagcgtcgca ggcaaggtga tatttcctcg 1260
ttgtgacccc aatgactgcg aaatatcatc tttctcgttg aataacgtta atcacataga 1320
ggtgtaggca aatggtaaaa cgtgtatcgc tgttccaaac cactgacggt caaaccttcg 1380
aaactgaggc tgcggccaaa gagcacgaag cgaagatcgc ggcgaaaacc accatcacgg 1440
cgctgttgaa gaagctgaaa ctggatggct cattcatcgg tatcggtgaa gaagatacgc 1500
tggcgctgga tacgttcctg ctcaacaacc gcgcggcgct gttgctggcc ctgaacggta 1560
acgtggtcaa ggctaaacag acccgcaaaa agaaaaccgc agtcccggaa acaccagtga 1620
aagaagaagt gctggcggaa ccggtggcag cacaagcaca accggcgacc gctgttgccg 1680
ccggcgactc tgacgcgcaa ctggactcac tggttgctga attaggcgca taatcatgca 1740
gacactgaaa aagctcgttc cgaccctggc cctgcgtcac cgtatgacgc agaaagatat 1800
ggacgcgatt gtgaccgata tccaggatca catcgctgcc gcactggcaa acggtgatgt 1860
tttcgcgctg ggcgacattg gtcgcttcat tccgaaagat cgcaaagagc gcaccggccg 1920
caacccgcag accggcaaag cgctgaccat cccggcgcgt cgccaggtgc agttcaaagc 1980
gtccagcact ctgcttgacg tcctgaacaa gtaatatcgc tgccgcccca cttcgggcgg 2040
catttctttt cccccaggag attccatgaa caaagagcca tcagccaaaa tcattgcgga 2100
tagcgtcggt tactacggcg gggcaatgag ccgcctaacc accattcagt tacgctaccc 2160
gcgccttgtc cattcggagc taatgacgca tcgcgtgttt agccgcaacg cctccagcag 2220
tcgtgcgatt ccggtggcaa aaatgattga gcaggttcgc accgacccgg cggcgccgta 2280
tgtctggaca acgaataagc ccggaatgca gggtgacgtt gtgaccgacc cggaactgat 2340
cgccaaatac gaccagatgt ggattgaagc ggccaaccag gcggcagata acgcagaagt 2400
cctgatgggt gaaggtctgc ataagcaggt cgtaaaccgc attctggagc cgttccagtg 2460
gatcagcgtt atcgtcacgg caaccgagtg ggccaactgg ttcgaattgc gcaaccacaa 2520
agacgcagac ccgaccatta agcgcctggc agaagtcatg ctggcggcga tggaagagag 2580
cgagccgaaa cacctgattg ccggcgagtg gcacctgccg tatgtgtcga aggaagagaa 2640
atccgcgctg ccaattgcta cgctggttaa gatctctgcc gcccgttgcg ctcgcgtttc 2700
ctacctgacg cacgacggcg cattcccgga tgtggacaaa gatatcgcgc tgtatgagcg 2760
tctggtcggc agtcgcccgc tccacgccag cccgattgaa caccaggccc gcgttatcaa 2820
cctgaacaac gacgagatcg gcctgaatgg caacttctca ccgttgtggg tgcagcatcg 2880
gaaacttctg gaaaccgaac gtctggtggc gtgatttgag tttggtgatg gcaatatatc 2940
gtccagagtt gtttgccatc acccggccct gcatcatggg tgtaacatcg aataatcact 3000
aattttcgag gagatagacc gtgattaaaa aactgttcct gctcatgatc ggcagggttc 3060
aacctgttga gtcagttaac gatgtgttgc gcagcctgtc cgacgaggta gaccgcctgc 3120
aagacattga gaactaccac caggatcgca tcaaagaact gcgctcgact atctccaccg 3180
cacaagcgga aattgaagag tccgagcgcg aacgtaaacg tgccagcagt gtggcagaga 3240
agctgatcgc cgtaatcgta aaatcgacca gcgtaattga cccggagagt ccgacagatg 3300
caaattcatg actatagcaa ggcagcaatc cgttccgaga gtaagatccc ggaagtgaaa 3360
ggcgtaggcg ctgtttccct tcacgcagcg ctgactgccg ttatcggtgt tggcgatgta 3420
atggatcaga tcaaaaagaa cgtgttttat aaccgtcctt acgaccgcga aaagctggca 3480
gatagcatta acgcttcgat tggcgccctg acgttcctct atcagagcgt tcagcctaac 3540
ggtggctttg ccgaccctga gcagagcctg gacattcacc gcatgacggc aaatgacggc 3600
ccgaccggta aggcgatcaa catcaacgcc gacgcgctga aacagattga tccgcgtatc 3660
ttccacgtta tcaccggcat catcaccgaa gcgtcggaac tggcagaagc gctgcaactg 3720
aacatcgaag gcgacccgct cgatctggtc aacgtgtccg aagaaattgg cgacattgcc 3780
tggtatggct tcggcatctt cccggatgcg tctgagatcc cgccgggcca gattctcgac 3840
accaacatcg gcaaactggc acgtcgctac cctgagaagt tcgacgcatg gctggcgcag 3900
caggagaacc gcgcactgga cgaagaacgt gagattctgg agaagggcgt ggaaaagcca 3960
ctggtcgcag gtgagccagg ttcaggcaac tgattggcat tgactgagcg cggtaaaagg 4020
cgctctataa taagatcaga acaaagcgcg acgagttcgc gctttttaat ggctcatttg 4080
agggatagga catgataggc atcgcgggtg cgcatagaac cggaaaatcc acactggcga 4140
aagagttcgc tgaccgttac gactgcgagt tcctggagac aagcgtttcc agtgtgtttg 4200
aggaaatggg cctcgatccc gctgtcacgt atgacttcgc cacgcgctta cgggtgcaac 4260
gggctatctt gaagcatctg gatcgcgtat acgggcaggc agaagatgat gtgaacaccg 4320
taaccgaccg cacaccgctg gatctgttgc tctacactta cgcagacgtc cagaacgata 4380
acctgacgga tgaagatgcc gcggcgctcg ccgagtatac cgctgactgc atcgaagtcc 4440
tgaaccgtcg attcggtatg gtgatgatcg ttcagcccgg catcccgatt gtgccggccc 4500
ctggcaaagc ctcgctgaac accgcataca ttgagcacct gaatatgctg gcgctgggcc 4560
tcatgagtga cgagcgcatc gaaacgcggg tggcatatat tccacgcgaa atgaccgacc 4620
tggacgagcg cgtagaggcg acattcaaca ccctgacccg tttcatcgaa cgttccgaac 4680
aaaacctcct gagcgagatt gagcgcggta acagcatcca ctaaacgccc caaccgcacg 4740
tattgtcact ccaagcaccc gtctttatca ttcgcatacg tcagaaattg aggtatgcga 4800
atgaaccctc catctatcgc cgaagaactt gaacgcaaga ccatcgagac aatcgactgg 4860
ctggttaaac gccggcaaga cggttttgcg tccgacgatc agctaaccat tgccgcagag 4920
gccctgtgga aagcaacgag cgggttattc ccgccggcat ccggtatggc tgacattatg 4980
accgaattga tgaaccttac gaccgcagag gcgaagcaga ttcgtcgcag cctgtgcgac 5040
acggaaggca acatcattac cttcgtttgg aaaatcggat acagccaatt cgctgttatg 5100
aagcgccaga tgggaacgtt ggtgggcggc acttcccgca cattgcccga cgcagcccaa 5160
gcaaagctgg cgatggatca aatggtagcg ggcctgattg aaaaagggtg gacgctatta 5220
tgattcgtga caaacgcagg cacgaggcgc cggaagatcg gcgcaattat caggacaaac 5280
tgaaccaacg ggaggctcgt caggacgaat ggagttgggc gcgtaaatcg gataacagcg 5340
aagatccgct cgtttccgtt gccagtgcga tcaacaaagt gaaggaggat ttaacgaggc 5400
tatctggaat gattgtttca acgcctagcg agcgcagcat catcaccggc ggaaggttcg 5460
aatatgtcct catggatgaa cttaacgcga aacgtgtgcc gccatatatc gccgacacaa 5520
aatgggatgg ctggaagccc gagccggaag atttacgcgg caaaaagaag aagaaatggc 5580
actccatgca gtataaagcc tacaaaaagt ggaacgctga ggccgaaatt cgtgaagccg 5640
tagagcttga aattgtcggt gaggcgcgaa ctgatttggg ctggggaggc ttctgatgaa 5700
catacgtttg gcgcggctta tcagtgatgg cttcttcggc ggtatgaagg agatccccat 5760
cgacatggat tgcttccatc atacgacgct ggtcgtgaaa gcctatcgca ccgactcgat 5820
aacggtcggc ggcgaagagg cggagaagct gtcactgcac tgcgccatgc ttgtgccttt 5880
tgaaacctgg ccgcatgacc gcaccactta ttccatgcag ccgatgcacg tcaataagaa 5940
aggccagccg tatcgttggc tggagttcac cctgacggcg caggaagatc ccgaagatgg 6000
ctaccggtcg tctttggaca aaatgttcgt ttctgagcca ccgacgtttc acggtggctg 6060
gacgccaatc acgccgaccg aagttgaggt gaagattgtc gaggagatgg cgttctttaa 6120
cctggcccaa tgccccgaag gtcacgacgg cacaccgctg gcgctggtcg aaatgggaac 6180
cctgcggcac gacgagtatt acccaacgtg ccgcctgaac gttaatattt cagtcatacc 6240
ggagaatgct ccgcgtaaac aagtgctgaa cgtggacgcg gtaattgctg catccacaac 6300
gtcagaaaag aacccaggct ggggtgattt ttagccgggc aaaacgctgt cagttccaaa 6360
gtgcggtcga tatcatgatc gcacgttcac aaataaggta acgcaaatgt cgcttccaag 6420
acctgacctg acgctcacgg cgtatgcagt gactctgggt ttcaaagttc gcagttccac 6480
ccacgaatgt ggcatggaca cgcccgtatt cgacgcgaag ggtgtgccgg ccgactccct 6540
gactttcgtc ctgcaacacc cgaaaggcga cgatattgtt gtctggcaaa ccgcccgggg 6600
ctggcgcgtc gcgcagaaac gtggcgaaca ctacccactg ccgcagaaca aggattttca 6660
ccagaacctg ttgtcggcgc tggacagtgc atacgccatt cggaaagaaa acgatttgga 6720
ttggcgcccg gccaccaggg tgtttacgct cccggccaaa gccgagcttt accgcatgtc 6780
gcccgacgac ctgttggaca ttctgaacgt tgtggacgcc gtgcagcgcg aagtgagcga 6840
cgcccggcgc gaagctattc accgcttggg cggcaagtct gagcacaagc gtattaaacc 6900
ccaggacgac gccacagagc agcaggcgta agtcgatacc atctgaaaac gaggcaatca 6960
tggcacaagc taaaaaggtc attatgacca aaaccaaaca gcgcgagatc ctgcgctcta 7020
ttctgatcgc tgtattcggc ccgcgcctga aagcggagaa ggaacgccgc atcgagtggg 7080
ctgaaaaact ggcccgcaaa gaagatccga agttcttcga gctttacgcc gacgagtcgg 7140
ctcgcccgta tctggactac aacaccagcc aaaccatcct ggtgcgccca cacctcaacc 7200
gccgcggtaa agagattgca gtgggtaaag gtgaaaagcc gtcgtcctac accctgcgca 7260
caccgtcgtt ctataacaac accaagaact gttcgagcga cattggcttg cacgcctttt 7320
atgacgagca caactcgtca tataacgacc gcccggcgac cgtctacgtc atgaaacact 7380
cgaaggacgt ggtggaactg aacgatgcag agtcggcaga gtattgggcg ttccgtgaag 7440
aagataaccg catccagaaa gacttcgaca cgctgaaaag cacacttaaa acggcgctcg 7500
cggcggcacg ttatataaaa gatttctata cagactatcc gcagttcagc cacctctccg 7560
acgagccggc cgaagtgttc ccggatgcgc cgctgcccgt tcctaccgcc agcactctgg 7620
tgaacttggt ggaaggcatg ggcctgcata tcccgtcacc cctggaagta aaagaggccc 7680
gcgatggaag tgagtaaaga ggaactttgc tcgccaaatg gcgagcgtca ttgggagcgc 7740
tgtcgcgcag cccggctgaa actcgaagtt ggtgatcgca tcctgattcg cgtcgtcttt 7800
gaagagaact ttggctggaa cggccgcatc gctcgcgagt tctggaaaga ggcgaaggtg 7860
gaaaaggcca ccaaaaccac catcactgcc gatggcatca ctttcatgcg tgaacgcggt 7920
ctggaacgcg ctggacaggg ccgacacatg gctgtctgga acgagcacga accgaacacg 7980
ccggaagaga ttgaagaagg cagaaaagag attcaggagc gcaagaagct gcgccgccgc 8040
attctcgaca ttgccaataa tgttgatgat gccgtttgcg acaaaagccg cgttaagagt 8100
ttggctgaaa tacagcggat cggcgctctg ctcgacgagt tagagactat cgttggcaag 8160
agcgagaaaa agcgctacta gcctctggcc aatatttcac atccacccgg ggcgcgagat 8220
aattctctcg ccctttttag aaggtctgag gcaatgttcc gagacatcat gttaattctg 8280
ttacccttcg tttgtggcgt tctcgcggga gttaccgtag cctacccgcg tgggttccgc 8340
accggttatg cgcgggccaa acgattactg ccgggtatgg ttgatgcggc agtgcgtgaa 8400
acttttgacg ttggaggtaa taaagatggt gacgagaatc agacgcccag gtaggcgact 8460
tctattcatt ctggcttgtg tcgttgcagg tgcaaccgga atgatgatcg catacggcat 8520
gttgacggta tcaaatctgc cgccaagcat gaacgcttat gagatcaaac aggcaacgat 8580
ccgcttctgg cacgaccagc agcgcaaagt cggatgctgg attaccgaag atggcggaat 8640
gtcgtgtatg cctgacgacc gctacacgcc ggtatcgagc gcagtgtcgg atgttccggt 8700
gctgaaaacc caaccaaaga acaataagga ctgagcatga aacgcaccct gttagcagta 8760
ggcttcgcac ttttctccat caccgcgttc gcaaacaccg acgccaaaaa cgatacactg 8820
gctgaaacgg taacgtcact ttgccatgac gccggggtaa caaaagttga catgccgaaa 8880
tgtgaaaaac gcgtccaggc gattgtggtc aacgccgtga tcgcgcacaa ttcggccctg 8940
gcctgtctca actcgccaga gaaggtgaaa cagttcggct taaacgagga gtgcggcgcg 9000
tttgaacgcg actcgaaaac agtcgatgaa tggcaacgag ccatcctctc cgcaccccag 9060
aagtaaccca ccaggcgccc gacaaagtat cgggcgcttt cacgttagga gtcttttatg 9120
aacccgtatg tttggagcga tttggcattg ttcggcattg tcgtcgttgt gattttgtcg 9180
gcgcccgcct attggctgtt ccgtcgcttc ttcccggcag gtgagagcaa ggctatcttg 9240
cgtcagcaaa tcacgcgcct ggaaaacgag gttgacgccg cccggcgtga aaacatcgtg 9300
cttaatagca ggctcctgga ggctgcggag agtaaccacg cctatgaaga aatgcagggc 9360
gagttggctg ggttgcaggc gaaactgtcc gaggtcgaag gtcggtatgc tgacgccgaa 9420
accgagatcg agttctggcg ctgtaaagat caagtgtctg ccgctgccga catttactac 9480
acattgggcc ttgattataa agaagaaatt gccaggtttg gttctgtcat tgcctgggtt 9540
gagcatttaa aatctgttta tgatcaagtg aaaccagttg cgggaatgat tcagcatgac 9600
gacgaaaatt gattttaggc cattagtgat tcagcgcttt attgacgctg ttttgcattt 9660
caacaaacag atcgcggtgt ctgaaattca ggacattttc ggtgtgtccc gcacgaccgc 9720
cagccaggcg atcaaagcgt atcgcgatca acgtcctgac acggcgcttt actacagcgg 9780
gtatgagaag ctgtggaaag cgaccgccga ctggaagctg accgatgaat attggcccgc 9840
caacgagcat ccggttcagt tcctgaaagc gctgaaaacc gtttacggcg tgaccatttc 9900
gttaacctaa aggaaggcgt aggcaatgca caaaatagac tcgaacccgg caccgaaaaa 9960
ctggacgctg tattaccgcg acggtctgcc aattatcggt caggcgtcgg tatcaatgcg 10020
ctatatggaa gaggatgaaa tattggagcg cggctacctg ccgtcacccg atatgccgat 10080
ctacagcgcg aagattcgcc caattggcac cgactgcacc gccacatcgc cggtgaagtt 10140
cattaccgac ccgctggtag gcaccggcaa ggtcatggag ttggtgttcc cgagccagga 10200
gattatctcc ttgctgaact acatcgccac cggtcaggtt cccgctgctg atggttggtt 10260
aactgtgcgt ttcacgttta aacgggttgg cccgcgcgtg ttcgctactc tctcaaacta 10320
tgctgagatc cctgcatcat gattgacagt gaaaagactt gggcgatctt ctggttcgcc 10380
atcgttgttg ccatttgcac cctgattggc tcatgcacca tcatgagcaa caatgaggac 10440
gcccggaaag cgcaggacat gaaatccctg attgccgccg ggcagtcgcc catcgaagcc 10500
cgttgcgctg tttacggcac cggcaccgat ggtagcgcct tagtttgcca aactgctgcc 10560
acatcggcag cgatcatgaa atcccttaaa gcaggagcag caaaatgaaa aacgcagatg 10620
tgttccaaaa gatcgccgaa gtggttcgcc tgaaagaagc cgggcagatt aacaccagca 10680
ttgcgctggc gaagattgcg gccctgtcca aacgctatgg caatagccat gccgttaagg 10740
tgaacactca ggctaacgaa gtgcgcatgg gctgtagccg taaaacgcag ccacgcgaag 10800
ccgcccgcca ttaataccct atgcacgtag ccaagcgcta cgtgcagttc ctcattccct 10860
ccccaagcac ccgtctttat cattgcgtta ccgtcaacaa caacgagagc agcaatgaaa 10920
atcatcggat cttttccccg cgccaaaggt tgggttgttc acttcaacgc caaaacaaag 10980
caggtttatg gcgactataa cgagccagtc ggtttaagcc cggagcaggt taatcgtcgc 11040
gccgccgacg ctcgcgccct tatcgcagcc aatcccgagc gccccgctga cccgccggca 11100
catccgggtt ggtcttacaa cgaacacgat cccgaatcgg tcaaagcatg gaaagcgaag 11160
gttgaggctt acaattacgc tcgcaacctc cagcagatgt gggataaagc caacgtagag 11220
cagcactggc gctactttga gtttgcgcca gtatttcgcg gtgtcggcgt tttcatcggt 11280
tacacccggg gccgctccag cgtcacgatg cagtttaagt ttgaaaccgg ctgcattctg 11340
gagatcgggc caagcggcat cgacaaattc atccagggtg ttcaggacgg ccacatcatg 11400
cgtaaagatg gcgggttcga cctgacgttc cgcatggaga agaaaggcgc taacgtctac 11460
atgtggccga tgttcgaaac agcggacttc gaaggaatga aatcgcatga agctgttatc 11520
gcttaacacg gagcaggcgg tgatcgagca tatccaaagt tccgggttta tgttcgttca 11580
tcgctataat ccgaaacacg aaacgctgcg ccgcattgcc gcgcgtatgc tgaaagaggc 11640
gaagctgaaa atgactcgcc gcacctcaac cggatgtgag tatcaggcac atgaagcgaa 11700
ttaagaaagc attggcgtgg atcggcggct ttatcgccgg ctgcgcacac gatacgggta 11760
aagttctgac ccaggcattc catatcttct tcgtggctat gtttggcggg gccgggttag 11820
tctctggcgg tctgctgggc tggcttttgt tcaaaacttg gtttggagta gacgcataat 11880
gggcgcacac ctttctgatt tgaaaccagg catggggttt atcgaccctc tcgccaatcg 11940
cattgtatgg ctctctggcg tgtttaagca tgacacccgc gcagagttca cttttatctt 12000
cgaggacgcg gcagacgccg gcaggcagcg tttcctgagc gaatctgagt ttatgagcca 12060
gttcgttcgt tccgagaagc acgaccgcac cgttgagcac ggctatcgca tccgtaataa 12120
actgagcgga aagttcctga acggctcaaa agaaacagcg accggcaagc agtggtcaaa 12180
gctgggccac ctgaaactcg ccattcacaa cgtctgcggg ttgagttcat atccgggcgg 12240
tgccgcgacc gacgccaaga acaaagcaaa ggttcaggcg tggctcgata agtatgaagt 12300
gatcgaggtt ggcggtattg gcaaccgcgt catgaaccct ggcgagtatc tcccggacgc 12360
gcacttggct gcgttgagtt cctaattcac tgtccaatgc tgaggttaga taatgactga 12420
gaagcaaacg agcaccgaaa cagacgttgt tggcttccct tgcaaccact gcggcacgac 12480
ggttgacctg tcaaaacatc cctatgatgc ctttgaccgc cggtttatcg ctgaatgccc 12540
ggagtgccgc gcacgttttg aagtagtgcg cggagagcat aagcaggtca acaaccgaat 12600
ggatcggccc caacgtatgt gaggttccga tgttaatgat tttgcgtggc gggttggtat 12660
tcgcggcgat tgcagtcgcg atttactgcc tgatttatct ggcaacaatg acgcgctttt 12720
tcgataaagc ccgtcgcaaa cgtatcctgc gccgaacgct gttcggtctg gtgtctgtgc 12780
tgttagcggg gctggtgttc agctccatca tcatcttgtt aaattaagga aaattatgaa 12840
gcgtattctg cttgggctgg cgatgctggc gacctgtttc acccttaccg gctgtttcgg 12900
catcatcgat cagggcaacg ttggcgttcg ctccgcgttc ggtaaaatcg atcagcaacc 12960
cgttaccggc atgtatcagt ctttcttctc cgacgtgacc gaatacacca cgaaggaaac 13020
gaacgtcacc attaccggca tgacgcctcg ggccaaagac aacctgacgc tgaaagagtt 13080
ggatgttgtg gtttactaca cgaccaacgc agccaagctg ccgaacttcc aggcgaccac 13140
cgccgggcag agcgccaagc tggatggtga cggcttctac cgtccgggct atgtcatgat 13200
cgatacgttg gcccgaagtg tgacgatgga ctcggtttcc cgaatggata gcctaaccat 13260
tcacgccaac cgcccggcgc tggagcaggc aattaaagcc gaagcgcaga agcaactcga 13320
cgctgcggcg ccaggcacgt ttaccataac ccgcattgtg gtaacgactg tccagactga 13380
cccaacgatt gagcagtcaa tccgcgataa cgtcaccgcc gacaaacgcc tcgacaccgc 13440
gatcaagctg acgaaggtga aagagcagga ggcgaagcag aacacgaaaa tcgccgaatc 13500
cctgacgccg gagttcctcc agcacgaata caaccaggcg attcagacct gcgccgccaa 13560
caataactgt cacctgatcg ttgatggcag tcagtcaggc aagattctga atatagccaa 13620
gtaacagctt ttcaccccta cgacagcccg ttatcttata gatacgggct tttttattat 13680
ctggagaaca caatgagcaa cgattccttg aaagaaattg acggtctgct ggatcagatt 13740
gaggcgaaag tcgcgaccat gatggctaaa ccggagcttg tcggaaccac cctgccaatc 13800
accacgaaaa tctgccacaa aatcgactcc agcgaactcg caacctgggt cgcgaaacag 13860
cttgggctgc gctatctgga aattaccgaa gccgacaatg acaccgatca cgacttcgac 13920
accaacaccc gccacactcc gcgcatcaat tgggagcgcg aaatggagag cattgacgag 13980
actctgaata aagccaaaga gcgcgggaat atcccaattt gggaagttag gaacctgctg 14040
aactatttcg ctgacgccgg gctgatcccg gaaggcaact acatcgtcag cgtgtcctgg 14100
tgatcgccat gaataaccat ccgagagtta aagccggcga aacgtatgcc ggcgttcctg 14160
accatatcga cgcgatgcgt caggcgttca ttgataaggg caaagagatc ggtgcctcac 14220
ctgaaagcgc gaccatcgca gcgggtcaga tcgcggcgtt cgctctgctg tattcaggta 14280
tgaattccac gaccattacg agcgatcatt gcatcgtaaa aatcgacatt ctcccgcctg 14340
aaccaatgac gatggaggct tgaatgacgg gcatccagtg caagtgcaag aaaggctatg 14400
tgtccggttg ggatggcaaa tgcggtaact gccggacgaa gcaggaacaa cgcgagcacg 14460
acaagacgat ggcagcgatg ccggaatatt cgcctgacgc gcacgccacc tatcgctttt 14520
tacgttgggg gaaataatgt ttatcgcatc aacctactgg aacggggcca tgtgtgtttc 14580
cgacatgcgc accgctgaaa ccgaggacgc cgcctggcgc cacctctttg aattggcgaa 14640
ggcgcagggt agcgctgacg aggagcgcga tctggagatc ttcatgcagt ggacacgcat 14700
ttacgaagtg ttcccggaca aaccgccgcg cctggtgagg gcgaaaaagg ggcagaaatg 14760
gctattattg gcgaaatcat tgtaatcatc atcggattaa tcgtgctgat cggtggaacc 14820
gccgcagcat acgccgctgc ggcgttcagc ggcaaaggtg gctggtttat gctcgtcacc 14880
attgccgcgg gcctggcaat cctctgggct gctggtcact acgggccaat caccatcgcc 14940
gttaaatagc caatcgcgcc ggtattgtct ccaataccgg tgcaatataa ttaccgcata 15000
cgttaaccca cttctgagga tcttatggca gcacgtagaa ggctaatctc tggatttgac 15060
agtgagacaa cgggcctgga aaacgaagat cgcgtgatcg agttagccat cagcctgatg 15120
gacattgaca ccggcgattt tgtttaccgt tacgagcagc gcttcaattc aggcggtcaa 15180
ccgatccacc cgaaagcgtt ggcagttcac catattcacc cggcggatat tgcaggttgc 15240
ccggactttt ccacctgcat tccaaccttc aacaaaatcg cgaccatttg cccgatttgg 15300
ctggcgcaca actccgagtt cgacctgcgc atgttggcgg cagagttcaa ccgtctgggt 15360
ctgccaatgc ctaacctgac cgttctcgat tccatgacag aagggcgctg ggcgacaccg 15420
aacggcaaaa gccccaacct gggtgagctg tgcttcgcgc tgggcgtgga ttatgacccg 15480
gcgctggcgc acaacgcgct gtatgacgtg gaggttatgc tgaaagcatg gcgtgcaggc 15540
tggcagcgcg ggttcttctc atacccggag gcagcatgaa tatcgccgtg cataccgcag 15600
tgatggcggc aaccatgcac ggcaacagtg tgccggatga ttccctgtcc ggcccgatgc 15660
ctgtctgggc gctggtgatt cttctctccc tgctgctggc gttcgtctgc tgcatgggct 15720
ggcttttcta ccaactttgg aagctgaaat gaaactgatt caaccgcatc tggagatgat 15780
cattcgcaac caggctgaca agaaataccc gcaccgcctg accctgcgcc tggccaacga 15840
aacggtgccg caatacaact tccgctgtca ttgggtggca gcgcaggcag cgaaaacccg 15900
tttcaaaggc gcggtaggcg tggttgaaac ggtcattatc tacaccaacg ggatcaccgg 15960
acattacgtg aacctgatgg aagatggaac catgtgcgac ttcacgctgg gcctggcgaa 16020
tgccagcgaa gatgtgcgcc ttattcgtca cgtccacccg gatgagttcg acaatatgga 16080
cgatgcgctg cggaacctga aaaagaaact ttgcgaaggc atcccggcgt attactccat 16140
gctctacaac ccgcaggatc tctgctgaat aggtaggtga atagatggat aagtccgaag 16200
ccactgattt gatgaaacaa attaaggcga atcacgccaa tttgaatagc tgcccgagac 16260
acgcttttgg caaggtagtt ggcgaccgct ccggtggcta cagcccgcgc cagaacatgc 16320
gcatctgtca gaactgtggc ggctcgatgg aagatcgcga cgtgatcctc tatgccaaag 16380
gctacaaagc ggccggcggc aatcctgacg atatcggctt attctgcgac ggtcaggctc 16440
tctgttagtt ccaacgcggg ttgccaagca gcccgctgtt ctctccaatc tcttctcgcg 16500
ataatagaca catagcgcaa caacgcgcag acaaccgcga gacatgccat gaaacctatc 16560
gccaaactta ccgtcgctga aattgcggca ccgctgaccg aaaccgagca gaacatcatg 16620
atcgccgaac tgtgcagcga cctgggcttc accaatcctg ccatcgaaag ttacgcgacc 16680
gtgagcggtg gtctggcttt ccctgctgag ttcgtcatga gtgttggcga aggcgatcac 16740
aatctgcttt acggcgtgac gccgggtatc gaaagcgagt attacccgga gtcgttcgac 16800
attaacaaat ggcgcttcac catttacctc cagaatgcgc cgaccgaatg cgacagcctg 16860
atgttcgcgt tcccgcatta cgatttagac gccatgaagc acatggcgga acttgccttg 16920
caggttgtgt caggcgatct ctcgtttgaa gagttcgacg ccgccaccga agattaccag 16980
aaataacgcc gcgcccgggg cttccgggct tttagctgga gagttgttat gtccgagaag 17040
gagtataaat ggtcgccgca gaacccaagc ccggctgcgg tggcgaaggt gaaagatccc 17100
atgccggtgc cgaacttctg cattcactgc ggaagccctg ttcgcctggg gacgcacgcc 17160
gagatctatg acgggcgcag ctttggtgtt tggccctacg tctacctgtg cgaaaacaaa 17220
gagtgcggcg cgtatgtggg cctgcattcc ttcaccaata tcccgctggg ccacctggcg 17280
accgaagccg aacgcgcagc ccgtaaaagc tgcaaaccgg cattcgagaa gctgtggaaa 17340
accggcgcag cgccaatgag tcgcaacgct gcatacgcct ggctggccga agcgctgcaa 17400
atcccacttg aaaactgcca ctttgccatg tttggcgttg agcgctgtga actggctaag 17460
aagctctgta aggcgaagta tcgcgagctt gttggctcta aggaggagcg atgaacgaca 17520
acaccggctg gtggttcttc ctggggatgg ttgtcggcgc cgcaattggt gctggctggg 17580
cgttcacttt tattctgtat ctcaaatggt aggcgtcgaa tgaaacaccg gaaagtggag 17640
acaacctccg agtattacaa cgcgatcccg acccgcttta agttgcaggc gaaaatcgtg 17700
ctggagcagt gggccaaaga cttcatcgcg cctgacaatg aactgtcttt tgccgagttc 17760
atcaaccaaa tcgtgccgca cttctacgag tgctggcgca tcatcatcaa cgcgcagatc 17820
gccaagaacc tgttcattgc ggcgatccag aaggttgacc caacctataa cgtggagaca 17880
ctcgcatgag cgaaattctg ccgattcacg cgctgaaagc gcagatcatc caacacgcac 17940
ttgacgcgct ggagtccgca ccgcacaact tcaccaacgc cgacgccaac gatgttgacg 18000
agctttggaa catcatgcgg gccgactatc ccgacaccat gcaggacgcg cagaatgaag 18060
tgcgctgcat gggccacaaa acgggcctgg ccacaccgag cgcccgtcac ctggaagttg 18120
atgccgttgc ggtgctgacg ccgttcaacc agtgggttgg cttctactac tggcacggcg 18180
gtggcaaaca ctccggcgcc gaagagatcg agtggatgaa ggacagctat tgggtgcagg 18240
ctgaaacaga tcaggtgctg cgcctggaac tcaaattcag cagcccggac ggtaagcctg 18300
agccatacga cccgaccgaa atggcagagt tctatcagcg cctggaggcg atgaataagt 18360
tctgtgcgcc ggtgcctacc gaaaacatgg cgggccagga cgtgttcacc tggattcaca 18420
ccgaaagcca aaggctgatc gccacgatgg gtgaagatgc ggccgcaggc gtcggcccaa 18480
tgaccgcctt taagaaagcg ttcggcgagg ggccggtcag cggcgttgtt gccaccctgt 18540
tcgcgcaaga gttcatggcg acgccagcca agaactatat cgaactgcac tacaacacgc 18600
cggagatggg taacttcacc gtgaccatcc agaagcacga tcacaagacg cctggccagc 18660
gcatcgcgga agtggaagat gaacgcgacg atctcctgat gcaactgaaa gacacggttg 18720
ccgcatggga gaaaggcgac gacgtgttcg gcggtattga acgcgcccgt cagttaatcg 18780
ccaaactgga agcgtaatat ggaaaacact ctcaccgacc gcgaacgcat tcaatttctc 18840
cgggcgtatg tgatggggat cgggcatacc gacggcacgc cgtttgaaga tgccaccgtg 18900
tccatttatg acattcgccc gcaggcgaac aacatcatcg gcatgaagga gtttaagccg 18960
atcatggact attatgcgaa gctgccgacg ctggttgaaa tgggccacgt tatcagcccg 19020
cctgagcagt tcgtttactg gatgttgaag gacttgggct tcatcaatgc gttttcgcaa 19080
ctcgccgatt acgaagcgag gatagcggca gacccggaga tattgaagcg agcgcggcgg 19140
ggagagtggg aggaagaatg aaagtagatc acaaacgctg gcgcaactac atggtgggga 19200
tcgcctggtt catcctgtgc attgcgcttc acttagattc gcaggcaaag aaacacgcca 19260
agccaccgca gccggtgcct atccaactcg atacgtggtc gctccgcacc ggcgacgcgc 19320
tcgacccagc gaaacgctgt gacccgccgg tgctgtatga agggcattgg tatccgatga 19380
tctgtccgat tgagggtgac ttccaatgaa taagcacgac cgcaccggca taaaagcggc 19440
acttcgccga cgcattcagc gccataccga agcgcaagtg gccctgagtt gggccggcag 19500
caaaatgcca gacgagcggg aagagatcga gcaggaggcg caaagcgccg ctgacgaact 19560
gcgctcctac ctcgattcaa tgtttgaccg cttaaagtaa cgcagacaag cgggcctcct 19620
gcgcccgctt tcgcaccgta gcgcccgccg tagcatttaa ccgcacactt tcaccctttc 19680
aaaatagaag cgcttaaaac gcgatacagc gcgtcaggcg accactcgat atgccgcggt 19740
tccaaattgc atagccaatg accgttttgc aaaatataag catctgaaag aagcaacgaa 19800
ggcgcaaaat gaagattctc cacatgaccg acccaggcgt taaaaacgtg attcgcagcc 19860
acccggcatt gcagggtaaa aagcagatcg ggcgcggttt ttattcagtt gtttttgaca 19920
atggagacac ggtgctcaaa ctgaccgccg acgcgcatca ttatgacctg ctccagtttt 19980
acgcagacgg gccgcacttc ccgaaagtga tcgtgaatca tggctgtgta ggcgagcaga 20040
agcgcggtgg cttcccgctg tatctcctgg agattgaaaa gctggtcaag atccgagcaa 20100
gacggataac tccggctggt ttacaaaatg tgcaaagcgg cgtcacgcat catggctgtt 20160
aaaacgccag tgttcgagcg tcacgccgac aagattgaaa tggcgcgtat tgtgccagaa 20220
acgttttacc agatggcgga agataaagac ttgcccgccg gcatccgtga ggggttggag 20280
cagttgggcc ggttctcact cgattacgac ggcgttggca tggactttca cccgaccaac 20340
ttcatgcagc gtgaggcgac aggcgaactc gttttgagtg acccgatcat gaatatcctc 20400
acattcaaca aggcgctcga agcgagcaag cggagctaat atggcaaaga aaatcaccta 20460
tcacgaccac gacggcaact acatgtcgaa agaggcgtgg gaagagaagc gtcaggacga 20520
ggattaccgc ctgatcaaaa agttcgacaa cggcgaagtc cgggcgttta tctattggga 20580
tggcgaaatc aaggatgccg ctgactcctg gcgcgatacg tgggaactgt tccacattga 20640
agtgtggaac tacgaccacg acggcaagat gaaggaagat ccggtcgagc acatggagac 20700
tttcccaacg aaagaaagcg tcatggagtg gtgggaagag ttcctgacca aatggactgc 20760
ggctgagaag cgcgaagtgc gtaactccaa aggcacctgg gtggagactt tcgttgaaga 20820
aggcaacatc ttcggcagcg gggcgccggg cgtcgcagaa gcgccgcaaa ctcaacctga 20880
cgacgacgtt ggagcgtggt gatgaaacaa ctcccgtttg aactgctgca tgaagcaggc 20940
gactggtgga aggttagcct gctgacgggt gagcgcgtcc tggccactga gggtgaagtg 21000
gaactgtggg gcgcactgat tgaactggcg aacgcgccgc gcgatcccgt cattatcgag 21060
cagccaacgg catcagttga tggcccgacg ctgaccaaaa acgaggcgag ccgaatcatg 21120
aacggcaccg cctttatcta tgaccaactg gacattatgg ggcaaatcgt gaacattcga 21180
gcatttcccg gcatcagcca ggcgctgcaa caggcggcgc tcatttacga cttcatcggc 21240
aaacgctttg gcattcagcc taagccgcgc aaaacaacgc aggctggcca gcctaccttc 21300
gctgacgtga tcaacgctga aatgaaaaag caggcagcga accctgacgg gaactatgac 21360
cagccggagt taagcgccga agaggttgca gcggcagagc aggcgcaagc agaagcgcag 21420
gtggcgaagg gcggcaatta cggcgggtgg taagatcagt tccaagttca atgtcctatt 21480
accgctgatt aatataaaac ctcgtcaaac gtgcgaggtt ttttattatg tccaaagcta 21540
tcattaaatt agtcgcagca agaactccat caggtaaaca aaaaggcttt cgcctcaaag 21600
ctgcaactcc taatatggca ggcttcaaga tgcgtcctat cgaaataaac ggtgaggttg 21660
aaggttattc ccggacttct acaccttgcc cgtcatttgg gcctatgtat ttaattcact 21720
caacaggcga tttaagtaat ttgacgcctg gcattgtgaa gcgcttttta gaatcgctac 21780
gttggaaagg ttattcggag tttgagtttt tgggtgataa cttggctcat ttgaataacg 21840
tatagcatcg ccaaatatat attactaagc tatttgtaag cggtgaacgt gagacactca 21900
ccgcttaccc aaccaaagaa gcgtccacaa attcaacata cggcattgcc gcccgccttc 21960
cctgcgggct ttttttttac gccgttggga agccttggaa cccgcgtggg agtaggcgtg 22020
gcgacgttcg cggggctgta acaaaaccgc tatcttcgcc tgtaactctt cactattata 22080
atcacacgtt atacaatctc ttttgttgta accttgtcat taaacgcttt atatagcgtt 22140
atatgcgccc ttatcacgct gttaagggcg cttttttatg cccgatatta attacaatgg 22200
cgcggcacat tcccaagcaa atagtatttc ttatcctaac acccgtctgt attatctatt 22260
catcgcaaca aagcgcgata aacacaatag accggaacaa aacgcggtct atataacggc 22320
agattgccgg tctatttaaa tatgaggatc tcataatggc tgctacaaat acttcttcca 22380
ccaaaggcaa aaaagcgtca accaaaaaga acgacgctcc ggttattgat caatctctgg 22440
ctgcactcga agagtcgctg aatgcaggcg aaaccatcac tcctgatgcg agcattcccg 22500
gcgctctcgt tgctgatggc ggtattgaag gcggtgtcga tggcgctgac ctactggcag 22560
aactgctggg tgaggcagaa atcgctgata acgccaacgc gcagccagcc ccgctgcctg 22620
agaacaccag caagatcgaa gctgccagcg tcaaaccgca accggccccg gctaaaccga 22680
acgacgccgc cggcactgtt cgtccgggcg tgagcgccaa gaccagcgag aaaatcatgt 22740
tccgcttggg tagcaaagcc ggtgacttcc tgattctcga aacgaaggac gcggagcttg 22800
acgagaaggc gttgcaggcc cgccaggcag aactgctgaa agagttcgac ggcaccagcc 22860
aaatcaaagt ccgtgagaaa atggtgcaac tgttcggcta cctctccggc accaacgcca 22920
agctgaacga agtaatgcgc cgggcattca ccgtcctgat taaagacggg aacctgatca 22980
gcggcgagaa aggcaacctc cacgttgacc tgctggcgaa accgtatagc gtcggcaccg 23040
cccgcgccca aagcggtcag attttcagcc tgttcccgca gttgaagatc gtcaacaaga 23100
ccgaccgtgg cgtgtatgtg gcgaacccgg acagcgtgat tctccagatg atgaaacagc 23160
gtctgggtct gtgataaaag cggtgccact ctccggggtg gcatcgggct tttatcagag 23220
gagaaacccc aatgactgat tacaacgctc aaatggcgaa gctgtccgat gatatggtcg 23280
ggcagttgtt tttggctgcg caacgggcgc ttgccgaacg tggcatccgg ttggctgacg 23340
ttgtgcgtcg gcagattcgc cgcggtgagg tagtttgctg gctcggcagt gacgaggaga 23400
tgcactacgg gatcgttaag gcgatcaacc agaagtccat cagcgtcatt gaaggcaaca 23460
agcacaaccc ggaagtgcct accggtgtta agtggaacat tggcccgtcc atctgcgttc 23520
cgctcgggcc ggtcaaacca acgggcctgg ccaagaaaga attgccgcgc ccggcgcatg 23580
agattcaaac gcagtcgcag gacgcgtggt aggcaacctg ccgcgccata gtgcaactcc 23640
taaaggcggt tgtcataatt accttatagc aacaacaacc gctaactaac cgaaaaacag 23700
gggcagatca tgaaattcca cttaatgcgt aaaccgtccg gctcgttgat cgttactcgc 23760
aacttgggct gtcagtatga agaaatccac aacaatttcg acaccgccgt tcgtctgttc 23820
ggcaagctgt gcaaaccagg cgaagctatc aatggcgctg aatgggagcg tcgcattctg 23880
gaacgtcagc cgattggtaa ggtcgccccc tatgttgacg cgattcgtgc ctgtatgctg 23940
tcagaaggca aacagccgaa agtttcacac ccgccctttg gctgggcttt tatgaaggct 24000
ctggtcaaag actttttctc aaaacaggaa gccccacttc atgagtgaac tccaaaagca 24060
aatcggcgat gatcaagagc tgaccatcca acaaatccgg gagcagttcg ctgctgccgg 24120
tatcgacccg agcgtccgca aagccgtgtt cgatgaaatc tctccgcttc tccagcaggt 24180
tcacgacaag ctggcggaag cgaaagtgcc gtatgttatg gcgctggata tctctgacga 24240
cgagagcatt gccgaaggca agagcctgtg catgtccagc atgaacatgc cgggcggcat 24300
cgtgtcgaac atgctgcgcc aggcggcaga gatctttcgt cgcaaagacg aactggagtt 24360
ggcgtttgaa tcactgagcg ccgacaacct gtttctggaa tgcaaacagg cgggtctgat 24420
tgagcacccg gatatctcca tcgaaacgtg gaaggagaag gttgccacca acgagactga 24480
tctcggctac tggcagtatg tttcggcggt agcggtgcgc ggtcttaacg agcaactgtc 24540
cgcgcaggcg atatctgcgg tgcatgaagc gctcggcggt caactgccaa cctcgggcct 24600
ggcgccagag gcataacccc tatcaagcgc ccttcttggg cgcttttcac tccagcacga 24660
tctccccaat gttccacatt ttctctccat aatcacggca gtattattct tttaccgaca 24720
acaacgaggt aaacgaaatg caaatttttg gccgttcttg ggatgaaatt caggttatgc 24780
agcaaggcgg gcaggctcgc aaagtagact tcgggccgaa gccagaagct accgacggcg 24840
acaaaaacct gctggcggtt cacggtgtcg ccaagctccg cgaaatgggt tattggggcg 24900
tgattgaccg cctgaccact tctggtctga tttgaagtcc gaacatcaaa ataataaagc 24960
tgtaggagac aaaggttatg gcacgtaaaa cccctgcgaa ggttatcgaa atcatcaaga 25020
cgcacgccaa catgcgcaac gggatcaaca cccgcgccgg tctgagccag gctgagaaaa 25080
tcgccgcgct cgacgccatc aacatgatga tggagagcat cctgcacctg cacaattgct 25140
acgcaggctt caaatatgtc aacgccgccg gtggcccgat caccgacgac tactaccgga 25200
cgcactccaa taccggtgcc aaagttctcg atccggtcac taacgccagc cacgattatt 25260
acgttcgcta ctgaggagaa cgccatgtcc tataccaaac tcgccacatc cggtcgtcag 25320
ttggatgaag aactgatgaa ggttgtttca ggcactcgcc gtgaactgct gctggagatc 25380
tatcaggctg gatgggagcc atgcagcccc ggcatcctga cgcacaaagc gtccggcatc 25440
acccagccga ctatgcacct gctggacaca ctgaccgccg acagtgccga cccgaactat 25500
gttcgcctgg tgtcgcaact gctgcgggca ggctggaacg tgcatcacga cgggcaggtt 25560
tatcacaacg atggacacgg cccaatgccg gcccacgaag ccttgctcgc ctgcatcaac 25620
gtagcgagtg aagcataatg gcgaagaaaa tcactgttaa agggtgcccc tgctgcgggg 25680
cgccagcgtt ctggacgata ggcaatcgtg aaacgcgcat gaatgatcgc accgtttgcc 25740
tggagtgtga tctggagatg gagggcgatt acacgccaca atcatcgctg gtcaaatgga 25800
actggcgtgt cgccgggcat tacgtgaaag acaccatttg gaacatcaat ggggagcgtt 25860
gcgagtagcc gcggttccaa cttttcactc caatacagcg tcgtcataat acacataacg 25920
acaaaacaac gcgcagaagc gcagacgagg atacaatgga caagaatcaa gctgacaaaa 25980
tcatcgaaac cctgaaagcg ttgcaggcgg gccaactcga cgacgcgagc ctcccgccgc 26040
acgttcgcga aatgattcgc aaggcgtctg aaactggcgc tcaggttgta gcggtttctg 26100
gcgatcaact gaaagagttg ggcttatcgc ctgacgcgct cgacatgctg attggtgacg 26160
gtttcacaat tgaagcctcc agcgttcgcg acacaaccga cccgcgctat gcaatcggca 26220
acagctatgc caaagaactt gcagatcgcg agttcgacct gatgcgccta atgtctgacc 26280
cgagcgcact gacaggcggt gaagcaattc gtttgcaggc gctgatcttc ggtaacgttg 26340
acgagatcat gaccatcgcc aaacgcaaga tggagcagga gccgaatgac ccgatggcga 26400
tgccggtgct caaaactctg gcgattctgc aaaccatcgg cgtatccaat atcttcgatg 26460
cgctcgcagc cggtgagaaa cgcctccgct ggcacggtgt ttccggtggc ccgcgtaacg 26520
tcctgcaaca gttctactcc aacctggtga acgtgatggc gatgaagttg catgtgccgc 26580
ctgtcgccgt gcgcgttatc accgaccaga tggcgcagga gattcccctg gcgccgctgc 26640
cgcctgagaa agtgttcgac gagaatttct ccagcgactt catgcgcaac gcagtgatca 26700
ccgacccgga gattcagccg ctggtgggcg atatgctgga cgcgatgatt gccgcaggca 26760
tcacgaaact gtccgacatt ttcagccaaa ccgatggtct gcaagatctc caggacaaaa 26820
caggcatgag cgacgaccaa actgcgctgt tcggcattct gctgcaacag atcgacggtg 26880
tgagcattga ggcgattgac gccacactcg aactcgccgg gaaggaagat catgagcgcg 26940
agcgtgtaga gcaggcgaaa gtccaacctg tgattatgct cgacgatccc gttgttattg 27000
cggcgcttgg cacgaacctg attaccacac tggagatttc aggcatcgtt gacctgcatg 27060
aagtcaccgg actgcgcccg agcgaagcag gcagagcaat tgccgaagca ttgccggttc 27120
agcaaaaaga gcttattcgc gaagtgtgcc gcttcctgaa taccggttgc gattgcgagt 27180
cctgcaacga gttccgcgag catttcgtga agatgaaccc ggcaatcggc gcagcgctga 27240
aagtgaaacg cgcccgtatc atccactaat tgaacacctt tgggcgcttc ggcgcccttt 27300
ttgcatttga gagatcccgc catgttgaat gacctgccaa ccgtctgcac ccaagccggc 27360
gcttatatca cccgctgcgg tttcagagca gacgtttacg ccatactgcc agcgaccgga 27420
accggcacaa cggagttccg cgtcaaaggg aacattcact acccgccgaa caacaaagag 27480
cgccgcaata aagtgcgcgt cgtcaccaag ttcttcacat ggcatgtatc cggccggagc 27540
tatccgctgc atgagtcggg gctggatatc gtcgatgttt ggccgcacgg agaggcgctg 27600
gtcgccatga gtgaaatgcc gcaataaaca gccgcagcgg aagttttact gtccaatatc 27660
aaagcgtcat gatctcgtta tcgacaacaa acgggaaata acatcatgac gctttcaaac 27720
acctacgcta ccgaatacac caaacaccaa tcacatatcg acgatatgct cgacgggaac 27780
gctcaggtgg agtttgaccc gaccgacccg gcgattaccg gtagtctcga cattcgcctg 27840
ctgctgattc gcgaaatgca gatcgaccac tttttacgcc aggcccgtaa cgagcgcgtg 27900
ttaggtaaaa acatcctcaa atcagttgag aatgtgcgcg accttggcta caccaacctt 27960
ctcgacgcga tcaccgacaa cgcaggcgac gaagaagatc agttcttcgc caagctgtgc 28020
gtcgcaatga caagcgtcgc ctttcagcaa tatttcatcg cacacttagg cgatgatgtg 28080
atgcagttgc ctgcggtgaa agacctcccg ctgcctgatc ctgaaccctt caaaatcaaa 28140
gccaaatcac tgcactgaaa agtgcatctg ctttcagaaa acgggcgcag tgcgcctgtt 28200
ttaattacag acgtggcgcc gtggagtaac taattgatat ataagcattt ctaggacatt 28260
caaccactat aagaaatgca accgtaacgc ccctgtaata cacccaggcc cgctataagc 28320
atttagaccg aacaagcaaa gcaaaacacc gtcaaaaacg agcagaatcg acccaccacg 28380
acgcgcaacc gaatcaaccc gacaccgaca gcataaagac acaaaaaccg cttagaagcg 28440
catacagaga gaatcccgaa atggagtctt tctccatgag gcaaaacaga gtctccgacc 28500
tcccggccag gacgatcacc caacccgcgt ttcccataag taaggtttta ttaaaggttt 28560
tgggtaaata ataaataatg gttcgcggtg gcattaccca agtcaaagcc caaacgcacc 28620
caaaccgcaa ccgaatcact cccggcgtga aagcccaacc caagcaattc agaacccaag 28680
gcaacgcaga agataaacaa caaccggatg cgaaacccga aaacgcagag caaaaacaac 28740
aaccgaaaaa ccgaacaagc ggaagcgaac tacaacacgc tggccaacat tcaaacccgc 28800
ataacgcata gagataaaca caacaaaact gaattgaggc agagcagttt cacgcatgag 28860
gaaaacaaca aacaaccgga agcgaacacg aacaacaaca ggaagaacca cacgactatt 28920
gcctgtaaat aacacaagga ctgtataggg taagacaggt ggaagtgagg ggttgggatt 28980
ggatcgttca atcgaaagct cggcggtgtt ttcccttgct gttccgctgc tatcggctgg 29040
cgttccgact gcgccaacct ctccgcttca tccatgaagg ctttccgggc gtttccgctg 29100
taaaccgcgc cattgctggg ctgtaaggct acttggtggg tggcagcttg ctgttctgct 29160
gctgataaaa gcatgacaaa tcgacccagg agacacaaca cggcagtgta taacgcctgg 29220
ccgtgagcct aggacttcct cggatagcca aggcaaacgg cagcgacggc gacacggata 29280
tcctgctttt cgtgagggcc aaggaagtcc tcggcaggtc agtttggaca gttccaaggg 29340
gtcaaagcct aggcttttgc ataaaacagg aagtcctagg cgcattaggc gcatatccat 29400
gcaattgagc ctaggcataa ggttttggca agtggatgtt ttccaaggct tttagcaaat 29460
ccgctccggg ggtcacatca aaaatagcca acgcatacat attcacattc cacatacgca 29520
ttgagacaat tctgatcgct gcaatgagcg cagcggtcta cagaagagag gcagtaacat 29580
gtcaccagaa caagagagcg tttatttgtc attgatgatg gatgtttacc gtcgtctgcg 29640
tgaatcggag aatagccgcc ggttcgttcg cgaaatcgtt ggcaagagca caccggagct 29700
acagcagatt gcgtgtgtgc agctttacct cgtcaccaac gttcatgcgt ttgctcctga 29760
cgaccacgct gttctgcgtg agtgtggcgg gcgcttcttt gagcaggctg ttgatgatcg 29820
cgatctgtcg gttgcggtag tgatgcagac cgacgagcag cgcgtggcgt ttgcaatgaa 29880
gatcgcgcca cgcattattg acctggagaa aggtccgttc gggttgttcg aagaggtgta 29940
gggttattga gtctcaggcc aggcgagtct ttaagcgtca ggccgtgagg ctcttttagt 30000
ctcaggccac cagcggagtt gatggctaca ggcaacgtta taaggaagtt aagagccgcg 30060
ttgtctctcc atataccgct gcatacgctt tagttatcga aacaacatga cgaaagaggt 30120
aattgccatg atggaagtaa ctcagtttgt gcagaactcg ccgaaagcaa aagctattcg 30180
cggcgacctc cagattacgg ttgcagaagt tcaggggtcg aacatctatg acgccatgct 30240
cgtgctcgat tttaagagcg acaaagcagg ctatgtgcag cgtcaggtga tgcaggcaca 30300
aatcgcagcc gtattctata tgaccatgct caccgaccat caggtcgcca acactgcgct 30360
gggccggata gtcaaagcga tgtatcaggc gaccaccttc aagcagataa aggcattgga 30420
gggcagaacc ttcacgaaca tcggggagat gcagtaagcc ctatgattaa gcacgccatt 30480
caaaccatcg cagccggtgc agcaatgatt atgctcgccg gttgtgtcca gcaacaacgt 30540
cagcctacca acgttgaggt cggctataac cagctatgcg tcggagtgga tggcgtgtgg 30600
tatgcaggcg acccattcgc gcctgttgag aacaatagcg cctgcctgcg tcacggtgtt 30660
cagcctatgt tcccgcagta agcctgtcgg cttgctcggc tcgtgagcct aggctttcca 30720
aggctgtcct tggtgaaacc aaacggcggt cgcggcgaca cttatatcct gctttttcac 30780
actacgaggc tcggcggctt tcggcttcgc ctcggctgtc ctcggaagtc ctaggcttcg 30840
cccgtgcgca gcgcgtcgga acgttcgcac gctaattagt ctgctgatag taactgaccg 30900
tgacgaaact attcgcttgc tatcggttcc gcagtcgcca gcggtatgcg cgtttataga 30960
tgaaacgggc gcacgcgcgt atagcacacg ttgagcataa agggaagaaa aaagaatgag 31020
aaaaaacttt gaaaaaaaga tgaaaataaa cttgcgttca aaatctgaaa gcactatatt 31080
aaacacatcg aagcgaaaca cgcgacgaaa cacaaaaaca taaatcaact gacaaggtat 31140
atatcatgaa aaacttcact actgctctga ctactgctct gaccaaccgt aacgctgttg 31200
caccgtcaaa agacattcag cttgcgctga acaatgctaa acgctttgaa aaagcgcttg 31260
attcactttt cggtaaagca gcttttgaca aaatcgctaa aaagttgatc gctcgttgcg 31320
aaatcgcaga aaaagcgggt aacgctaatg actttatcgc ggtcaaagtg cttgtgaaaa 31380
tcgttagcgc gtcggtcgct atcgcgcaga aaaacacaag cgtattagac ccgtatagcg 31440
aaaccatttt gcgcaacctc gttacgctgc aaacggtcaa caataaaacc gcgctcgtgt 31500
cgctctctcg ttcgattgag tataccgaag ctgaccagca gcaagcgatt aaaacccgct 31560
acaattgcag cgcgggaact gcatcaacgc aagcaagctc aacccgcatg atgctcgaag 31620
cgctcgacat ctgcgacgtg caaaagggca aaaaaggtga cgttatcagc tttaaagaga 31680
atgaccgcgc ccgcttgatg gttagtctct ttgcagaagt tgaaccggta gaagataccg 31740
aagcacacga cgaaaccgaa accgaaaacg cataacaaca aagggcgcac acgttgcgcc 31800
cttctcactc tctgacaagg tgaatttaaa atgttcgatt ctctgaaagc gttaaacctg 31860
acttgtgttt taaacagtat tgaaaatgat cgttttaata tcagtgtcgg taatgctgat 31920
aacatcgcgt ttacttctga ttttgactat gcgcagatcg ctttcaatgc tgaatatgtg 31980
ttaagcggta gcggtgcatt tacccgctta atgtgtgacc tgaatagcag cgacaacccg 32040
cacgatctaa tcggtgtagt gtatacagac actgttacca tcagtgacta taacgcgctt 32100
gattgtagcg tctatgtgaa gtcacacgaa agcgctctct ttgtgtctgt cgtgctgact 32160
gacaacgggc aagcggttta cagtcgcacc gttgacgtgc tacgcgacga aatgacagac 32220
ggtgaagaaa acgacatgtt aaacaacgcg caacgctacg cgcttgataa ggtgtttacg 32280
ctcgcaatgt tgcgtaatga gttagcgcaa catgtaacat cacgcagcgt aactaatacg 32340
catgatgata gttacggtgt gttattacat agcatgaata acatctgtga ttactactca 32400
ttaactaact aatcattgca tagcgtgaca atcacacatg taattgtcac gcttgaaacc 32460
gtttcacgtt gcaacaatac cgcgctgaaa agttaccgtg tgaaactatc acggtatgtt 32520
aagagtccta gaaatcagag cgacctgctc aggcacagcc ttcctcttat ttgccctccc 32580
ggaacccatc cttatacata ggggccaggt caggatatcc ctatccttat agttagccga 32640
cctgtcagga attggcgagc cgaataatcg ccgaccggta ttgcttctcg cgctccatcc 32700
agaagtggac agacccgcca aagaccgact tgagcaattc cgccagttcc ctgtcgatgg 32760
acaaactgcc agctaacagg cgggccagcg tcaggtcgtc catatccagc agacctttca 32820
cataggggat agaccagtcg ttctcttcca taatgtcagt gatggtgtcg ccgggcgcag 32880
acgcccaatc aggctcaaac gcggcacagt cgcactcagg ctcgtcagca ggctggcgcc 32940
aaccgcagga gcaatcaacg aggtcgccgc agccaccctc caggtagttc ccgcagtccg 33000
ggcaatacag taatttcatg gttttctccg cagttcgttc agtcgataac tccgcctttc 33060
cgcagctcac aacgccactg acgcagcgtt ttgatctggt gcttaccagt gcagcattca 33120
gttctttgtt gctcacacac gaacacagtg cccgtgttcg gcaggcgctg gcgtgtcact 33180
ttccacgaaa aacgccgccg tcggcgacaa ttcgcttcac cgcggccgcc cgcgccgccg 33240
cggaacaggc gacacctgaa agtgcgaaca accgcgtgtc agcgcagcca gcgcaccttc 33300
ccacacatct tccgcgcagc aggcagcggg tgcgcacagt tgcccttata cttcggcgtg 33360
ctgccgacat tccggccgtc agcgcgtgat gtgcgcgcaa tccctcaaaa acgtcgtggc 33420
ttaccattcg ccacgccatt accctccaac ccgcgaggca atctcgtcgt caccattgat 33480
ctgtcgtcat actgcctaac gcgcacgtca tggactgtct cgcgcattgg cttgctgggg 33540
aaattgacgc tggcgaactt gatgaactga ttccggcggt agacggactt tttctcgccc 33600
catttcatga accggacgat ggcgccaacg tctttcccgc gcagcagcaa ctcaatggcg 33660
gtgccgtatg ggctatgcgt gtggaacccg acctctgcct gcgccatgcc gcgcttattg 33720
ctgattgcgt aaggtagaac gaaatagggt gagacattcg caacctgatc acccacccgc 33780
agcccgacgt tctccagcag gtcgtccagt tcatcagcgt tgcgaatagc ccggatagtg 33840
tcgtgcgacc gactggcctg ccagataacc tctttgtcgt gaccttcctg gcttttggtg 33900
ttgcgcatca tgatcacaac cagtttggcc ccgggcatta acggaatgag cgctgaaagc 33960
gcgagtgcag tttcctccag gcaggggcca ccgtataaca gggatgccat gtctggggag 34020
ccggttccgg ttgggccttc tgttccgatg tagaacatag cgccgcagtc atacccaatt 34080
ctgcgtggct cgcggggaaa cacctgcatc agtcgccagt gcggcgcgat ctccaggagc 34140
gtctgttcgt cggtctggag gtatttatcc ggcgtcataa tgccgggtgg ctgtttgctc 34200
attttcttat acctgctcaa aaatttctct gaggcattga cacaggcggg aaaaggatta 34260
attattatct cgcctacgct ttcagattgc tcattgctta ttcacgattt gttgctgttc 34320
caaaagcccg tcactgctct gacgggcttt ttatttgtct aaacaaaagc atatcgtgct 34380
gactttgggg ttagaagcga cttttcatcg ccttttcttc ctcttgcgat atttcctgcc 34440
ctgacaggat gcgttccata tcatcgacca aagtcagaag cgcttcggtt ggcttcgggc 34500
tgttcctgat accgatgatg atccccttca ccttgtaatc gcggaaccgc atttccagcc 34560
tcatgcagca acgtcgcacc gccgcatcgg gttcttcacc gtagagcgct gccatccagg 34620
cggcgagttg caggtgcagc atggactcgt aatagtcctc accccgggtc ggcgattcaa 34680
agcgtgttat ttggcgacgc gccatcagcg ccgcgagtgg attcatcttc atcaaaattt 34740
actcttttcc agttggccca tagaaatgcc ggccgctatt ttcgatatgc cggaggtttc 34800
ggactcgggc gtaattgagg tgccgaagat cgctgcgaaa tcctctgggc gtttaatgcg 34860
catatccaca gacggcttca ttgtgatgta tgtggaagag tcgaaaatgt cgtcgccttt 34920
tgccattttg gcgtcgcgct ccttctgctc cttcaccatc ttctcgatca tcttgcttgt 34980
ctgttcggtc agcattgcct ccatcgcttt ccgctcgctc tccatacgct cggcagcttc 35040
ggctttgatg cggtcttgct cctgcgcatt ccactgttca gccatgccgc gccaggaata 35100
cgccaggctg ataaagaacg ccgcgccctc gtcggtatag ggcgagtatg gaacgtgcgg 35160
cagaagcaga ttggtgcctt cctcgtcgat atacgagtct ttggcctccc ctgccgctgc 35220
ccggcgggcc acgcttttga agaggttctc ggcgagatac cggccaagct ccaccggctg 35280
ctcatggttc gccaggagat agttgatctc gtcattgtcg gcagagttct ccacctccca 35340
agcccaagac atgcggccgt cgtgcttgaa gatcttcttc ttgggttccg ccggcggttc 35400
ttcccgcgtc atgatctccg ctatcgccgc gcttatctcc ttcgcgtcaa tctcttccgt 35460
gcgctcgggt tcggatatta acggcgtgcc aaccatttct ttgacctgat ggatgatctc 35520
ttcgtccaga atcttttcaa cttccaactc tttggacttc aaaatgctcg ccagtcgcga 35580
caggcccgtt ttcagtatgc tttcactcat tgccattgcc taaaccccac tcaattgggc 35640
tgttcacact ggagtgacgc gacttttcgt agatcgcatc gtaatagcca gccatgaacc 35700
acacgtaatc atcggagtgc ggagagaact tcactgcgct gatacgccgc agctttgcct 35760
gatcccgccc attgctccac atataccaaa taatctgccg gcgccgcttg tcggacgttg 35820
cgaggtcttt ctccagcaaa gccctcgtct gttccaggat cgtcgcgttg acgtggttca 35880
ggatgcccga cagcgtttta atctccatca gccagccttt tcatttcctc cgccctctcc 35940
cgagcgcctt caatgtagcc atagcacagc gcggcgccac gttcggtgta ggggctttcg 36000
ttcaactcca gcggaacatc gttcagcgcc tggcgccgcg ctgcataccg caggtcgata 36060
atttcgccga gaaacctctc gttacccgtt tcctgtatgt ctttgcagat caggttgtag 36120
cgctggctgt attcgttgta attctcaacg gtcggcttca ccagggtgtg cagttcgaag 36180
tcctgaatga gttcatcctc aagcacgatc tcaaatggct caccgctgaa cggatcaata 36240
ccgccgagaa ccggtttccc gccgccgacg gccattactg ctgctccgct actttcttag 36300
cctgacgctc gcgctggtag atggcccacg gtgaggttcg gctgttaact ttggattcgc 36360
gccgggcagc aaacgctgcg ttgacggctt cttcggagtg gcccataaag gcgacaaggg 36420
tttcgatcac ttcgccctga gtcagcttgt gggttttggc gaggtcagca atcgcgtcct 36480
gcgcgaccgt gtccagtgaa aaggtgtagc gtttgataac tgtattttgc atgggaatct 36540
cccggaatgg ttgacgtttt tctgatgcta aaagtatagc gaaaaaagtc tgcaaaattt 36600
catcatcaaa cgctactgcc tcaaattgtc ggtgtgaagc caagccccgc gaagttgaac 36660
tcggttccgg tcgggatgat gttctccgca aagcctggcg tgccagcgat gatcgcgtgg 36720
cgctgctgga agtgaacttt gaggtggtcg ttgtaaatgt cctcaaaatc cacgatgaat 36780
gcgacgttcg ggccagtttt cttcgcacgt aagccacgcc caacgcgctg ccgcagcgca 36840
acctcagcct taccggcgcc cgccaggatg atcatgccgg ttgccggcac gtcaacgccc 36900
acatccagaa tcgtggtgcc gatcagcacg tcgattttct tgtcagccaa ttcctgcaac 36960
gcagccttac gggtagcgtg gtcacattcg ccgctgatga agcgcacccg caggcccgcc 37020
agcgtcagca tgtgtttcag gagatcgcca tgcgcggtgt gctgcaccag cgccataacc 37080
gacagaccat agcgatgcgc cttaacagcc tccgccacca ccaactcgtt gcgctccttg 37140
cactcgacga cgcccagacg gtatgccgcc tgccaaccgg tgtggcgata cagcttcggc 37200
ggtcggtttt tgatggtcac atacttaaag aacggtttgg ccaggatgcc ggcgtcgata 37260
agctgtttct ccgtgacgcg gtagccaact ggcccgcagc acgccatcag gcgcatgttc 37320
gcttcctcgt cgtccttcat gaacggagtg gcggtcaggg ccaggcggta atgcgcgttt 37380
acgcagtgac gcataatgtc gtaatacgag ttgccggacg cttcgtgggc ttcttccatg 37440
atcacgcact cgaacttact cagtagtgcg acggtctgat catgcagcgc ctgctgcacc 37500
gcaatgcgtt ttactgcttc cttcttgatt tgctcggcgg tagcgcgggc ggatttctgg 37560
cgcttcacca gttcttctac agcgtgagcc agctttttcg ggtcgagtgc tttgtgtttg 37620
cgcttgaacg ccgcaacttc cttctcttcg gcagcgatca gggagtcgta aatctcctca 37680
aactgctgcg gcagggtttt caccgtcagc ctggcggtca gcgtctgcac catgccgaca 37740
cacatcggct tgatggtcat ttggcccgct gcgtttacgc tgccgaactg gccatcgccc 37800
agcacggagc attcaacgcc catgtccttc tcgaatgagt ctttcatctg atacatgaga 37860
agggagcgcg tcgtcaggaa tagcgtcggg cggcgaatcc gggcgtaaag cagcttggcg 37920
atacgggatt taccgccgcc ggtggctacc tgcgcaatca tggcgccatg cttcaccacc 37980
ttttcgacga tctcaggctg gtaggagtag cgcgggtcgt ctgggaatga gtcaacccga 38040
gcgccgacaa tccccagggg ttctggcaaa ggtttgcgca ccagattgat cttgtgacct 38100
tcacgctgta atttggcgac caccagcggc acgaacccgg cagggaaagt gcaggagcgg 38160
aagtcgaaga atgaggaacg gccatcccac gcagatgcct tgtatcgcgg ggtgttctct 38220
gcgccagcga ccatgtagga caggatctgc tgaaccttga gctttacctc acgacttggg 38280
tctttcagtt tggccgtcac cgcgtttctg gcgatagtta ctgtttccaa catcatgtcc 38340
tcaattgcca atataagagt gcttgcgcta gtataaggca ttgatgcttt tgcagccata 38400
tctataagga tcacccaatg agtatgcaac ccaaagcgca aatggccgac ccgcgcaaac 38460
tccgcccaaa cccctggaac accaacgtcg ttgatgccgc caacgaggcc aagctggaag 38520
agtctctcaa aaagttcggc atgttcaaac cggtaatcgt gcgtgaactg ccgaccggcg 38580
aactggaaat cctgggtggt gagcaccgcg ccggtgccgc tgttcgcctg ggtatcaaag 38640
acattccgat catgaacctc gggccaatcc ctgacgcgga agcgaagaag atcggcctgg 38700
tggataacgg tcgctacggt aatgatgaca gtctgcaatt ggcggcgcta ctgaaagagc 38760
ttggggatat tgacgatctc gcgtcgttca tgccctacag cgatcaggac ttcaacaaca 38820
tcatggaagc ggccgagatc aacctcgacg atctggaagc actgccagca ctcgatccga 38880
gcgccacacc ggccccgctg ctgtcagccc cgccgacgca caccatcatg cgcttcaagg 38940
tgccaatcga agatgccgag cgcattggtg agctgatcaa ccatgtaatc aaaatccagg 39000
gactgagcgg aagcgacagc ctgacgaatg ccggcgatgc gctggttcac cttctgacgg 39060
ggattgatgc cgaatgaaaa agattgaact gatcgatctg gagaaactcg ttccctacga 39120
gcttaactcc aaaatccacg acgacgcgca ggtgaagaaa atcgccgagt cgattaagca 39180
gtttggctgg gatcagccga ttgtcgtcga taaggacatg gtgatcatca aaggtcacgg 39240
ccgcagcctg gccgcgaaac tgctgggcgt taagcaggtt ccggtgctgg tgcgcgacga 39300
cctgacgcct gatcaggttc gcgccgcccg cctggcggat aaccgtgttg ccgtcggcgg 39360
tatcgacacc gaactgctga aacaggaact ggccgcgctg gactacgacc tcggggatat 39420
cttcgacgcg aaagaactga gcttcctgga agccgacctg tcggaaatga acatcgaggc 39480
gttcgtgcca gacctgaatg aagcggttgc cgcgcagtct ggtgagtcca ctcgcaagat 39540
cgaagcagtg gacgagcgtc aggtgaacat cgccagcgct ctgggcttca aaaccatcca 39600
ggggaaagac gagcaggcta tcgcgttctt catggccatc atcgaaagcg aaaccggact 39660
gaccggcgcc gaagcgttcg tgaagttcgc cagcacctac ggggcggaag aagagaatgc 39720
ctaaatacat catcgacaag cggttcaact ccgaagtaga ccggactgaa cgtgtgctgg 39780
agatcgccga atcattcggg ctgggcctgg acgacaagga gtttgtcgtg ttcgacaacc 39840
aggagattcc ggtcgaacaa ggcaacgtgg tctacatcac tggccagtcc ggctccggta 39900
aatcggtgct gctgcgcgaa ctgtcggcgc aaatgactgc cgccggcctg aacgtggccg 39960
atatcgacaa agtggagttg aagccaattc cgctgattga ccagattggc aaaaacacag 40020
gggaagcgct caacttcctc agcctggccg gactgaacga tgcgtatctg ttcatccgta 40080
agccgagcga actgtccgat ggacagcgct atcgcttccg cctggccaaa gtgattgagt 40140
ccggcgctca ggtttgggtc gcggacgagt tcctcgcggt gctcgaccga accactgcca 40200
aagtgctggc atacaacctc cagcgcactg cccggaagat gggtgcaacg ctgatggttg 40260
ccacaaccca catggatatg gtcgaggact tagatcccga tctctatgtt gataaacgtt 40320
atcgcgaaaa aatcacaatc aaggtgaaag agaaatgatc cagatcacta ccgctccgca 40380
atggctgacc aacgtaatcg agcactcgaa gaactctccg gtggcggtta tcttcacctc 40440
tccgacctgc gtgccgtgca aagagttgaa gccgaagatt gaagcgctcg ggcgcaaggt 40500
gttcgaagtg gacgccggca ccagccgcga tctggcagtg ggcctgggtg ttcgcgcagc 40560
gccgacggtt cgcatttaca aagatggcga gatcattttc caggcagttg gcgacaaacc 40620
agaaattctg gatgcgctgg ttgaacatat caccctgtaa gcgctaaatt cgtcaacgaa 40680
acggggtcag gcgcccgcca ttcagctaag acgctaaatt gcgtgtcctg acctcaaaac 40740
ctctcagaat cgctctcaga gcgtttggcg ggcatatgaa tttctttgaa atgatggagg 40800
ctgttcggac aggttcggtc actcgcctgc cgcattggcc aatggacgtc tacctgatga 40860
tggttgacgg tgcgctgttc ctgtttaacg gtcaggttca tgagccatac acgccggatg 40920
atgccgacga gttgagccat gagtgggtta tccttccgca gaacggaggc aactggtaat 40980
gagcaagaag cccaatccaa aacgggatct cgccggcatc acgtcgctcc agattcctct 41040
gttcggcggg tggctgatgt tgacgctcga ccgtgatcag cacaaccgcg caacgaagtg 41100
gctggggcaa ccgccaagcc cggacgacga tttcactggc ctgggcttct gccaggagta 41160
tgacgacaaa gaaggtcggc agtgcatcat tgtccacgtc agcgattggc gcctggatac 41220
gctggtgcat gagattgcgc acgcggcgtt taaaatcctg gatcatcgcg gcgttgaaac 41280
aggcagcggc aatcgtgaaa cgttctgcta cctgatcgac catctgttcg ccgaactcta 41340
cccggcaacc acaatgcgct ggcaggaaga acaagacaaa ttagaggcta aaaaatgatc 41400
ctgcttgata acgacgacat tttcctggag cgccggcctg gcgccggcaa taagccgctg 41460
tcgctcctga aagacattta cgttgagcgc ggcactatcg acgactggaa cctcctgcat 41520
gagcttcact acaaagcgga gaacctcggc atcgggccgg tgatcttccg cgcggtgctg 41580
gaggggcaga cgattggcgt cggcgtaatg accgtgccga agatgctctc ttccggtcgc 41640
aatgaggtgt tcgaccacct gcgcccaaat cagggtggcc gcgattccaa gctggtgaac 41700
acgcaccgcg ccaagtggat caacgccaac tcctgcacca acagtcgcct ggtgctggat 41760
acgatgtatc gcggggccgg catcgcctac cggatgcaga acatcatgat gcgtatgtca 41820
gccaaacgcc tcgtggagtt ccagtccagc atgtcgaagt tcaatccgtt cgcggcgcgg 41880
gcaggggtga agtttaccgc cccgaaacgc tcgtccaact acgagcgcgg tctgcaatgg 41940
ttccgtcgtt ggtttaagtc caacccgagc gactacgtgg gcgtgatggc tgaactaaac 42000
tcatggccaa agccagtgcg cgagaagtgc atcaaggaga tgcgcaagtt ctattacgat 42060
ttctccagca tggagaagtc cggcgacaac cggtttaacg gcacgagccg cgttgagggg 42120
atggaagttg gctacctgct caagtcattg cagcagcttg tcctggccag cccgctgtat 42180
ggggtttacc ctaacccgga ctttggggtt acactgcccg agcgaattga cattttggcg 42240
ttcgacaacc agccggttga cgcgccactg gatttatcga aggtgagaaa atgggattaa 42300
cgacgaaaca acgagcgctg atgggggtga tcgtcgccgg taatgacgac ggcacgaacc 42360
tggatatcga tcagatcctg gaagcactgc cgtatgacac cagcaaagag agcctgcaat 42420
tctctctccg cgcgttggtg aacaaaggct gcatccagaa aatgccaacc gagactcgcc 42480
gcggcagggc gcgggtgatt tatgccgcga ccgcgtatgg caacagcttt ttcatggcca 42540
gccacaaaga ggttccggtg ggtgaagaaa ttgacgcccc ggacgtggat acagcgattg 42600
agatcccgga tgtgtatttg gggttgggtg tagagccgga ttaagtcgat tacccaagtc 42660
ccaacccaga gtttatgcgg gtttcgcgcc cgctgctttc agattctgaa cgggcttggg 42720
taataccacc ctcacccata agtatttata tacccaaaac cattattaac ttttaactta 42780
acaattattt ttcgggtcgc gatggcgatt gcccaacgga gatgaacatg gcgagcacag 42840
agttagagat cggcatcgtc ggtgaggaat ttgccccggc ccggaacctg aacgcgaagc 42900
tcggaaagct gctcggtgtg aaacggggcg aaccctgccc gcgcttttct accgatcttg 42960
acttcaccgc ccggctgcta aaagaactcg atacgcaccc cctcacagcg ccaacgctct 43020
ctggggagca tgtctgcgta tttcatcgaa atggcgtcgt tatggtgact atgggctgca 43080
aaacagcggg tcaggcgcaa gctgtcgccc tgctgtattt gttaagcgtg agcgaaaacg 43140
gttaaactcc agtccatttt caaagtgtaa ggattttcaa gtgactacac cggccgtaaa 43200
aactccaaca cgaatgacac cgcggcaatg ggcggaagca gaggcactct gggaagcggg 43260
cgaggtaacg cttgatgatt tggcggcgcg atttgataag gatcgctcgg cattcgtccg 43320
ctacttcaaa aaacatggca tcgtcaaagg gtcgcgagca gcagcccgga aggaagaagt 43380
caaagaggcg gttgccgcgg caggtatcga cgaagcgact gtcctggcca accgcatcag 43440
ggaaaccaag gaagatcact acaaaatgtc ctccgcgctg gcaaagctgg tgtgggcgga 43500
agtgctgacg gcgaagaaag acgagaagcc attcagcgcc atcaaagaca acctcaaagc 43560
cctggacaac gccatgaacg tgctgatgaa ggcgcgtatg gagcggttcg ctatccttgg 43620
cctggataaa gacgactacg tggacgagga tggtctgcca gaactggtga tctccgaact 43680
gaccgcagcc caaatcgaag aactgcggaa ccgcgacgaa gagggcttgg aagccggcac 43740
ggccgtgatc cctgaaactc tccaggaaga aattgaggac gaggatgaag aggacggcat 43800
tgtggaagag ggcgatgatt aatggccaag gtcagagcaa gcctcagcct ccacccgaag 43860
cagatggagg tctaccagtg caagaagcgc tttcgcgtgg tggtcgccgg ccgtcgttgg 43920
ggtaaaacgg ccctatcccg agtcctgatc atcaaacgtg cgcagatgcc gcggcagaaa 43980
atctggtatg tcgcgccaac ctaccgcatg gccaaacaga tcatgtggac tgacctgctg 44040
gaagcaatcc cgccgaagtg gatcaggaag attaacgaaa cgacgctgag tatcaccctg 44100
gtgaactcca cccgtatcga actgaaaggc gccgacaaag ctgactccct tcgcggggtc 44160
ggcttgaact tcctggtgct cgacgagttc caggacatga gccaggacac atggacgaag 44220
gttctgcgtc cgacgctggc ggataaacag ggtgacgcga tcttcatcgg cacgccgaag 44280
gcatacaact acctgtatga agtctataag aacggcaccc ggggcgagta ttacgaggac 44340
gacaaaggcc ggttgcgcaa aaacacctgg cagagttggc agttcccaac catcacgtcg 44400
ccgtttatcc cgatttcgga gatcgagtcg gccaaacacg atatggacga caaatccttc 44460
aaacaggagt tcgaagcgtc gtttgaaaca atgtccggtc gcgtctacta tccgtttgac 44520
cgtggcgatc acgtttccga gaaagtgcag ttcaacccta aactgccaat ttgggtgggg 44580
atggacttca acatcgaccc aatgagcacc gtgatcttcc aaccgcagcc ggatggttct 44640
atctgggcgg tggatgaaat cgtgcagttc tcctcaaaca ccgaagagat ctgcgaagag 44700
ttggagaagc ggtattggcg ttaccaaaaa cagattactg tgttccctga cccggcgggt 44760
ggccagcgcc aacatgcccg gggcgagact gacatggaca ttctgcgcga gaagggtttc 44820
aagaaaatcc agtatcgcaa gaaacacccg gcaatcgccg accgtgttaa ctctgtcaac 44880
cgcatgttaa gatcggcaga tggcaccgtt cgaatgatga ttagtccaaa atgtaagtcg 44940
ctgatcgctt cctttgagca gacgatttac aagcctggaa cgcgtgatgt ggataaatcg 45000
accggcaccg agcatagtgc ggatgccgca ggctactgta tcgagcttaa attcccgatg 45060
cgcaaacctg tatacggtgg tatcagcatt taacttatac ttgtgtggaa aaattcacta 45120
ggatatattg cagccatgaa aaatcgcatc tcgcaagccg gcgctacggc agtgattgac 45180
ccgcaggagg ctgaaatgac gccgcctggg gccagcacga cttcaaaaca gttgaaggaa 45240
ctggttcagc gtcgccaccc gcagtttgaa gatcacctga cgcattgggc gttcctcgaa 45300
gccacctatg acggtgggcg cgagtggttc aaagagaaca tcttccgcta catcaaagag 45360
ggtgacagcg agtttaagga tcgcgtagag cgtgcctatc gcttcaacca cacccgcgaa 45420
gtggtggact tgatcaacaa atacctgttc aagcagaaca tcgtccgtaa cgaggaagat 45480
gctccagagt ccgtgaagaa attctggaag cgctcgaccc gtaacggcat gggtatctcc 45540
gacttctcgc gtcagatctc caagaaaacc tccatctacg gtcgcgtggc gattgtggtt 45600
gaccgcacca ctgccgaagg cgaaatcgtg tcgaaggcag acgagaaagc ggccaacctg 45660
caaacttacg cctacatcgt gccgccagag caggttttgg actactctta cgacgagcag 45720
ggtgcgctta actggattct gctgctggag caggtgcgtg acgacgccga cccgctgagt 45780
tcttctggca aggttggggt gcgctatcgt ctgtggacga aagattactg gctgctgatc 45840
gaagagaaag gcaaaggccg aaccaaaacg tgggaaatca cggatagcgg tgcgcatgac 45900
ctcggcgaag tgccggtggt gctggccgac cacattgttt ccgacgacct gtatgtaagc 45960
ccggcaatga tcgacgatat tgcatatctt gaccgcgccg tggcaaacta cctgtcgaac 46020
attgatgcca tcatccagga tcaaaccttc tcccaactgg cgatgccatc gcagggtgtt 46080
tcaccaggcg acgacgcata cgacaagatg aaggagatgg ggactaagcg tatcttcctg 46140
tatgacggcg gtgaagcggc taacaagcca ttttatctgt ctcctgacgt gaaacaggcg 46200
caggtaatca tcaccacgat caagacgatt attaacgaga tttatcacac ggtagggctt 46260
gcgggtgaac gcaccaagca agacaacgct cttggtatcg acaacagttc cggcgtggcc 46320
aaagcctacg actttgagcg agtgaacgct ctcctggcgg ctaaagctga cagcctggaa 46380
atgaccgaga acaagatcgt gcgtttggtc tgcctgtgga acggcgaaaa catgcctgac 46440
gaagagaagg agttcgttac ctatccgaac aacttcgaca ctcgcggcct gtatgacgag 46500
ttcgacctgg cggcacgact gatgttggtg gacgcaccag attctgtccg tcgtgagcag 46560
atgcaatccg tgcttgataa actgttcccg caactcccgc aagcgaagcg cgaggagatt 46620
gaaaaggaac tgaaagattg gccaccgcag gacgtagttg acccgttagc agatcctaaa 46680
tctctaccgg cagacgcggg ccaggcggct aaacaaacca ataccgactc tgcgaaaaat 46740
atttccaaag cggtataaac cctaacagcc aagcgaatgg ctattaaaag gatcgaaaca 46800
tgaaattccg aaacatgatg ctgaaatact actctcaggc gggcgaaggc ggtgagggtg 46860
gcggcggtgg tgctggcagc gaaggtggtc agggtggtga aggcggcgaa ccgccggcga 46920
aagacccatc caaagagcct ggcgccgaag gcggcaaagg tggtgaaggc ggtcagggtg 46980
gcgaaggtgg taaacctaag ctgtcggaca gtgaagccca actgctgaaa gacatgatga 47040
agcacaagga aactgctaag tcagaaaaag ccgcacgcga agcactggaa gccaagctga 47100
aagagttcga aggcatcgat cctacagccg ttcgcgaact gctggcaaaa cagcagaagg 47160
ctcaggaaga ggaactggag aagaaaggtc agtgggatgc cctcaagcag aacatgatca 47220
aagcgcacag cgaggacaaa gccaagctgg aagcgcagat caccgaactg caaggcgcgt 47280
tgaagtctcg cgataacact atcgacgaac tgaccattgg ctctcaattc ggcaactcta 47340
agttcctgaa agaagaaacc actctggcgt ctgctgccaa agcgcgtgct ctgtatggca 47400
accacttcga actggttgac ggcgtgctga ctgcattcga taagccgaaa ggcgcccaga 47460
accgcgctcc gctggttgat gcttccggta atgcactgga tttcgactct gcgatgcgta 47520
agatcatcga gtccgacccg gacaaagacg cactgctccg caccgctgcc aagcctggcg 47580
ccggctctgg tcagaaagct gccatcccgc ctaagaaagc tggcgcggtg caggaagatg 47640
cgtcaagcgt ggataagatc gcttccggtc tggctgggtt gaatatccaa accaacaaca 47700
tgtgatcgct taattgatgc aggcagatat agcgcggatt tgcaacagga ttaattcgtg 47760
ctatattctg ccacatcgag tcataagcga ccttggccga ttcaactgaa cccttaattg 47820
gaaaaggaag attaaaatgc cattgcttcg caccgaatcc gagaagctga gtaacaacca 47880
gcttatcgca ggcgtgatcg atgaaatcat cgaccgcgac gacctcttct ccatcctgcc 47940
gtttgcgcaa gttaacggta aggcgtatgt gtataaccgc gaaaacaccc tgggcggtgc 48000
gaactggtta gatccgaacg acaccgttca ggaaagcgca gcaaccttct ccgaagtcgt 48060
tgcaacgctg aaaatcctgg ctggcgacgt tgatatcgac aagttcctcc aggctactca 48120
gtctgacacc aacaaccaga tggctattca gatcgctaaa aaagcgaaag ctgtggcccg 48180
cgagttccac aaagttctgg cgcagggtaa ctccactacc aacgccaaaa cctttgatgg 48240
tctgagcgtt ctggctgacc aggcgcaggc tgctgcggca actgtaggtg gtcaacaggt 48300
tatctctgct ggcaccaacg gtaacgcgct gaccctgacc atgctggacg aactgtgtga 48360
cgcagttccg aacggcgctg acgtgattgt gatgcgtcgt ggcaccatcc gtgcctaccg 48420
cgcactgctc cgcgcaacct acggcaccga cgccgtgatg cagcagttgg aaaacttcgg 48480
tcgtccgatg ctgactcaca acgggattcc gatcatcatg aacgaattcc tggcggctgg 48540
cgaaactatg ggtagcaacg ccaacaccac ttctgtttat gctctgcgca tgaacgaact 48600
ggacggcctg cacggcctgt atggcggtca gaacgctggt atcgttgtcg agaacatcgg 48660
caccgtccag aacaaagacg ccacccgtat ccgtctgaaa tggtattgcg gtctggcact 48720
gaaatccact cgttctatcg cggctctgcg cggtgtaacg aacatctaag tgccagcata 48780
agctgatacg ccaaggggcg aggccaaaag cctcgccttt tttattgctc tcaggagata 48840
aagaaatgtc agaattaaag gttatcaagc tcactcagcc cggctacgaa aacttcaccg 48900
gacagatggg ccagattgac ttcacggacg gtcaatcgga ttatggtgtg tcccctcaga 48960
aggcagcgac cttcctgatt aacatcaccg gcgaatacgt cgaaccagca gcggctcaaa 49020
cgccggcccc tactgaataa gacataggag aaaagcaatg aaactcaaac tgactgccgt 49080
aggctacgag aatttcactg gtctgtttgg caccattgaa tacgttgatg gcctgtccgt 49140
cagcgatgtt atgccgcaga ccgcaaagcg cgtggcgtgc gttatctccg ttgaatggga 49200
agatggcacc aaagttggtg ttgcggatgc cctgatcgca aaccagaaca tgccggcccc 49260
taacgaaaca gcgaccattg ttccacctgt gccagaggcg ccagtagtca acactgtcgc 49320
atggacggaa gaagaacttg gcgcagtcgc tgatgaaaaa ggcattgccg gtctgcgcga 49380
gatcgcggaa ccacacggca tcaaaggcaa ctccatcgcg ggcctgatta aaggcattat 49440
cgaaaaaagc gtagctaaag aggcgtaatc atggacaagt ttctcgctgg cgcacctgtc 49500
acgctgacga tcccgctgca agaccgcctg ggtaataccg tagcggcgct tggggtggag 49560
ttcgaagtgc tggacagggc tggtgccgtt aaacaagccc gccaggctgt aaccgtcagc 49620
ggaaactctg tggaagtgac cgtgacctcg gcagcgaacg aactggctga cggtgtgccg 49680
cgcgacctgc gcaccgtcaa actctactgc cagattgatg gtggcgagca aacgatctcc 49740
agatcgtatg tggtggaagc cgaagccatt ctgattgttg gcgtcaactc gttccagacg 49800
ctcgaagaag ccgaactgac ggcaatggat atcttcgaca tgggcgattg ggatgtgatg 49860
gacgacgacg acaagattcg agcgctcatt gatgcccgga cgcgcatttg cggcatgacg 49920
ttcaacctgc tcgacctgta tcgcccgcag gataacgtca gctacgtgcc ggaaggcgtg 49980
atcggtatca gtaaaggtgt aagcccctgg aacatcaaaa accagcttgg cgatatcacc 50040
atcgagcaat acaacctgct cccggagaag ttcaaacagg cgctgcgact cgctcaggtt 50100
gccgatgcgg cagcaacact gtcgcctgac cctgtagagc aaaaacgcgc caaaggactt 50160
atcctggaca ctatcggcga aaccaagcag atgttctcca gcggccgtcc ggtcagttct 50220
ccggtcgcta aaaaggcgat ggactacctg cgtgagttcg ttgttaccgg cagcgcactg 50280
aaaatcggac gaacctgatg aaactcgata tgactctggc ccggcagcgg gccaattacg 50340
atctgcttct gaaagccctg acgggcattt acctgccgcg tgtaatgcct ggccaggaag 50400
tgacgccggt ggcgctgaaa caactgcgcg atgaaggccg gcgcctgatc agtaacttcg 50460
ggaagcaact gaaagcagac attcaggcgt tcaaacagga actcgggtat gaaacgagcg 50520
actacgacgc cgaatacgag ccgcagctaa cgcgcctgct gcacgataac gtcgccacca 50580
tcgtgaaagc gctacgtgcg agcaaagctg atttggcagc gatgctgggc ggtggccacg 50640
gtgctgtggg tgaaatcatt caaaagcgca tcactcaacc cgagtttaaa gcgaccgata 50700
ccgcagaccg ctcctgggaa gcgccgaagc tgttcaactt cctgctgcgc aattatctct 50760
actacatgga gatcagcgcg accattcagg acattcgaaa cagcggcagc gacctggccc 50820
ggctgaaata cccgaacccg gaacacaaga acgccggtat ggtgttctcc atcgacggta 50880
agacgcctgg ccataaaacc ctggccgaga tcaaagcgtc ggtgttccac tacaacgcaa 50940
acgcggaggt ggaaggtgta tatccctaag aaccgctgtg tgattcagaa ggcggtcggc 51000
acgaacgttt atggccaaca gcagcctggc gccacgttca aagagcgctg cgccatcgtt 51060
gcgatcatcg ccagtgacaa gaaaacgtcc gttcgctccg atagctctgc gtcacgcggc 51120
aacgcccatg aactgctata cgatgcggtg attctggtag gcccgcgcac gaaggcggca 51180
atgcacgaca ttatgacggt caacggctat aagctggaga tcatgactgt gcagccgcgc 51240
tacgatatcg acggcaaact ggatcactat caactcgacc tgcaaatctg gacgaaatca 51300
tgaaactgat gccgttgctg gagttgctcc agatgaacgg gcttggcgcc gcaggcaccg 51360
acctgtttct gaacatgatg ccgagcaccg tgacccgagc cacaatgctg cgcgagccac 51420
tgaccggcac cgagatcaat cacgaactgc cggagtatta caagaccgag tttcaggtca 51480
ttgtccggtc gccagattat gaggacggcc tgcgtctgat taacgatgtg gtgaaggcaa 51540
tgacgctgga ggaagagtgg gtagaggaca tgtatttccg ctactgccgc ccgaaagcca 51600
aaccggtggc gttcccaatc tctgatgggg cgttgatcga atacaccgtg aagatgtgtg 51660
cctgcttcaa cgaagaggac taagccatgc cagtgcgcgt gacgggtatc gtggagacac 51720
aactgatgct tgcggaggta gggactaccg cccggcgccg cgccgttcgc aagctgcatg 51780
agaaggcgct ggagatcgca gagttggccc gaaagtatgc gccggtggat gaggcaaacc 51840
tggagaaagc cattaaggtg ttcccggaga aaatgccaga gacacgcgag cgtaacgcgg 51900
cgggccagtt cgttaaacag gatgttttcg tatacgttga cactgacatg gctgtgccgc 51960
aacgcccagg caagacagtc ggcgattatg cgtatacaat gcacgagcac ctgacgccgt 52020
tcggcccact caacctgggt gagcggtcgg cggagaagca atccggccaa agagagatgg 52080
tcggcgggaa atacctcgaa cgcgccatga atgagatcgg cgaatcggta attggagagg 52140
tcagtatttc agttctgaac cgcttcgact attgacaagc catctggcag acgttatgag 52200
gctgtgttat agttcagccg agtcaaacct ggctacactc tcttttgcaa aggagttttt 52260
agaatgagcg ataccaagaa cgtaaaactt ggtgtgtgca aagtgttcta cgatggcgta 52320
gacctgggct acacccaagg cggtgtcgat gtgactgtga aaacggaaac ccacaaggtt 52380
aacgttgacc agttcggcaa aaccaccatc aacgaagtta tcctgagccg cgacgtgacc 52440
gcgaaaactc cactggcaga aaccacgctg gagaacctcg ttaagatcat gccaggcgct 52500
gtgctgaccg aagttggcgg ctctgctgca accggcacga tcaccatcgc gaccaacccg 52560
accgacggcg acactgttac cgtcaacggc gtagttgtca cctttaagac ctctggcgcc 52620
accggcaatc aggtcaacat tggtgcttcc gcaggcgcaa ccgcaaccgc actggcagcg 52680
ttcctgaacg cctccagcct ggctggtctg tctgtggcga cctacaccgc caacgcatct 52740
gccgtgaccg tcacctatga cgtgaaaggc attgcgggta acaacttcac gctggcgtct 52800
ggccaggctt ccgtcaccgt ttccggtgcg aagctgtccg gcggcaccgc gtcctccagc 52860
aaacgtgttg acgtgcctac tggcatcggc gcgaacctgc tggaaagcgc gaaagaactg 52920
cgcctgcacc cgaaagcgct ggcggatacc gacaagtccg aggacttcgt tatcccgctg 52980
gctgcgaccc caggcgcact gaacttctcc taccaactgg agaaggaacg tatcttcgag 53040
gtggaattta acggataccc tgatccggcc accgacaagc tgttctacgt cggcgcgtaa 53100
tgccaaccag ccccgtcagt ttggcggggc tttatcacaa ctcattgtgg actaaaaccg 53160
atggctaaga ttctcaatat cgactccttt gcaaaggacg agcgctctat caaacttggt 53220
ggcgttgaat acccgatcaa agaaatgacc gtggacaact tcatcgaaac aacccgtcag 53280
gctctgtctc tggaagatgc caacctcgtt gagcaggttg aaggcacgat caaaatgatc 53340
atgcgctcta tcccgacagt gccggaagat gtgttgcgcg gtattaaact ggaacacctg 53400
caaactatcg tggccttcat tcgcggcgac catctggtcg aaggcgttga agatacggat 53460
gccgccacaa aaaaagagcc agtgaaagcg accaaagcga cgacgaagaa gaaataaagc 53520
cggttcgtcg gatgaaggaa atcgacctcg gtttccttat cgcccgcttc tcacactttt 53580
atgcagtaag cccagacgcc gtgttggaaa ccccaattcg gcgtttttgg tttatgaacg 53640
gctgtattga gcgcataatg gcgcagaaag acatgagagc cttaaccgta gctgcggcgt 53700
cgcagtcagg ggaaggagca aagcaatatc gcgagaaact gtgcctggac atgggcgaga 53760
tctacgtgat gaacgaattt tacgacgctc caccggtatc taagagagat gaggctggct 53820
tccaagcgtt gaaagatatg tgctaacaac gttaatttga ggaaccacga tggccatcgg 53880
cgggaatatc aaggtaacgc ttacgctgga cgacgccggc tttactgtaa aaagtcagca 53940
ggcggcttcc ggcatcaaga acatgaactc ccaaattaag gggttcagtg gcgggcttga 54000
gaaagcggaa accagcatca aacgattagg cgagcgcgtt cagaccgtat cgaaagagtt 54060
cacggcgctg aacaactacg ctaaatcagc gtccaaaaca ctcagccaac tcgcgagcag 54120
cgggcagacg ttggataaaa ccaccgcaag cctcgttgcg tcctttgcga acctgcaagg 54180
ggttgtgagt cagttcgcga acaagctcaa cagcgcaacc gacggcatgg ggaaagcccg 54240
taacgccggc gatgcactgt cacgctccaa ccgcgacatt ggcacttcca gccaggcagc 54300
ggcagacggc ctgacccgac aagagcgggc ggcgcgtaac ctcggcacgg cgcagcagca 54360
gaccaccaaa cagatccagc tttccaccct ggcggcgaaa gacgctgcgg cacgtcagtt 54420
ggcttctgag ttctccaaaa acgagcagtt agtcgccaac aagaaagcag cgctggcgtc 54480
catgcttcgt gcagagcagg cgtatcagcg tcagcttgaa gaagccaaag cgcgggcaat 54540
ggctacgtcg atgaagatcg acaaccgtcg tctgcctaac ggtcgtatga cctccgtcaa 54600
cagcgactat atgcgcgacc tgcgcattca gttggagctg gagcaacggc aggtagcggc 54660
gctgcaacag agcgtcaacc tgatcggcca ggaaactgcg aagatgcagt ccaccatcac 54720
cgccacgcag cagcgtaacg ccgctattcg tgaaggtgtg gcactgcgcg agcgtgacct 54780
cgccaacgtc aaccgctacc agaccgcgct tcgcgaaggc aaccaggcga tcctgaatgc 54840
tgagaaagcc cgtcgcgctg aaatccaggc gcagaacgcg gctgtcaaag agcaaatggg 54900
gatggtcaaa tccctggctg cattgtgggc cgggatgaag atcgaaggcg ccctcatggg 54960
gacgctgcaa accgccgaaa actacaacaa cgtggtgcag cgtgttcgcg ccgcaaacat 55020
gggtggccag gcgggcgtaa acaacaccat tcagggtgcg cagggcttgg cgcgtcgtca 55080
gggcaacctg tccgacgttg aagcgctccg catctacatg ggtgtgcaga ccggcctcca 55140
gactaccgac cgtcatgaac tcgacgctgt ggcgccgcag atcgcgactg tcctgactga 55200
cctgaaacaa ctgttcccgg agagcatcca taacttcgaa aacgcctctc gaaacttgac 55260
cggcgttatc gaaacgatgg gtatcaccaa agatcagggc aaacaggttg aagtcctgca 55320
aaacatctac aaggcaatcg ttgcatccgg cggtaaggtg acgactgagg acgttgaaac 55380
gctgatgcgt ggcggcggtc ttggtaacgc cgtgaacaag tctggcgact acctgctgta 55440
tgccatcgca atgtcgaacg ccctgaaagt aatgggcggt ggcggctccg gtggccaggg 55500
tggcgtgtcc agtcaaggca cgatggaacg tatgctgctg aaacttgcgt ccggcggttc 55560
ccgtctgacc aagcagggcc tgaccaacat gaccgacttt ggctttatcg acgcgcagcg 55620
cctgaatgaa gccaacccga aaggtctgac ccgaaaccac accgctgttc cgtgggtgaa 55680
ctccaacatt gcgcaggaga acatctacga atacgccaag tggttcggcg acgcgctgcg 55740
taagcagatg gcagacccga ataacagaaa ggctgatcgc ttctttgata agggcgcaga 55800
ccgtaacgac ccacgcgcac aagcaactgc ggcgagccgt ttcatcgacc agtccatcgg 55860
ttcgaagaac gccccggaga tgctgaaaat cttcacgaac aaagacgccg ttgaccgtat 55920
ggatcgcgaa gtggtcaacg cccgtaatgc gcagacgccg gagcagacca aagggaacct 55980
cgaccagagc tacacccagg cggttgcccg tatggatgcg cagttccaga acctcggcaa 56040
aaccatcggg aacatgctcc agaagtatgc gatccctgtc gttgattgga tcgccaactt 56100
aacgcaggcc gtcgataact tcatgaaggg caacccgtta tccgcagagt ttacgctgtg 56160
gggtgtggct atcggtggcg cggtgctggc gttcaaaggg ctgaccggaa ccctgggtgt 56220
agtcggctca gtattccgtc tcatgaccgg catgggtggc gccggcgcac aagcggccgc 56280
aggcacggct cgggcagcaa ccggtatgtt ggggatggtt ggcccggcga ccgcagcccg 56340
taacgctgta ggtggcgtgc gcaccgcgtg gacgactatg gcgacgaaca tcgcggctcg 56400
aaacaccgcg ctcatgacgg ccacgaatgg cgttgtgacg atgggcggca cgttccgtat 56460
gttcggcacc gtaatcggca gcaccctggg cttcatcggt aaagcgttcc tccgcgcgat 56520
cccgttcgtt gggtggttgc tggtcgcctg ggacttgggc cagattctgc ttaacttcga 56580
agttggcggt gcgaaaatca gtgagtggct caccaaatgg tggggcgatc tcatgaccta 56640
cgccaaaacg aagtgggaag agttcaaatc catcttcaac agcgacgagg ctgacgagaa 56700
agcaactcag gctgcgattg cgaagattaa ggcagaggct gacgctcgcg gtaaagagtt 56760
cgaagccaaa cgcaaagcga accaggcagc ggctgcggaa gagaagaaaa agcaggaagc 56820
caacagtgcg aacgcagcgc agagcgccgc agagcttggt ggccaaccgc cagaggttgc 56880
cggtggctac ccgcctccaa accaaccagg cccgattgcc aacaatgaag gcattgcgct 56940
gaactatggt caggacaaac cgcagcgcgg tttcgaagat ccgttcacca gcagcctggc 57000
cgaaatgcgt cgtaaagcga ccattgacgc gcagaaagct ggcgctgcaa tcgctgacac 57060
cggcaacgac ctggcggcag aagcccgcac cgcgttccag gagaaatgga tcgctggcga 57120
cttcgacccg gggcatgacc cgaacaaacg ccagttcaaa ggcaaagacg gtcaactgga 57180
ctggaacgca acagggcctg gcggctcgcc gcaggaatgg gttgatcagt atgtcgcgat 57240
gaaacgcgca gaagaacaac tcaaatccat gcagttcgtg aaacagcgtg tggccggggc 57300
cgaagaggac ttccgcaacg caatggagcg caccagcggc gaaaccggta aacagaaccg 57360
tgacctggcg gcaatggagc gtgaactcgc ccgcgccggc gaacgtctga aaacaggaac 57420
tgctgattgg gcggcgtggg cggctgagaa gaaccgcgca ctggaaacca aagcgggtgc 57480
cgtgctggtg aacttcaccg ccgacttcgc agaggacgac cgtaagcaga tggcgaacct 57540
catgccggac ggcttcctga aacagaccgc agaaatggac gcggctattc agaaagaccg 57600
cgagcagtat gaggaactgg cccggaacca caaaaagtat tacgacgacg aactggcggc 57660
atacaaggcg cagttggcca acaagcagat cgataacgcg ctttacaccc agaaggtgac 57720
tgaggcgacg cagcgctaca cttcctccgc ggagaaagct gaaactgcgt atacccaaca 57780
cgttcaggtg cagaaccagt tacgcctgcg agcggctgaa acggctctcc agaaacagac 57840
ccgcgaatgg cagaacactt acggagcgct cgactcggct accgctaagt gggccaacag 57900
catgatggat aacctgtcca ccgcgctgac tggcggacgc gctgactgga aatcgttcct 57960
gaccggcatg ttgaccgacc tgatgaacat caaactgaaa gagggcctgg gtggactcgt 58020
aagcgggatg ttcggcgggc tgcaaaacat gctcaacggc acgctgttca ataacgccag 58080
cacggcgggc agcggcggtg gcattatgtc cggtctgtcg tctatgtggg gtggtgtgac 58140
cagcatgttt ggtggtggcg gtagtggtgc cgcggcaagc aacgcaaccg gcacgaccgg 58200
cgcgggtgcg ggcgcaacat cgaacaaccc tgccgcggca gcgacgactc aactggctaa 58260
cgccgcaggc accgcgaccg acaagctgca aaacatgagc aacaccggca tcatgggtgc 58320
gatcaccagt atcggccagt ggattgtgtc gctgttcaca ggcaccacag cgtctaccgt 58380
gaaggcgacc gcagacacca ccgcggcgac cgccactgta acgttgagca ctgcgatgtt 58440
ggaagctgca ctggcggcaa ccaacctgtc tatcagcctg actgccgcgg cgacgaccag 58500
caccgcaaca gcagcattcg ccaacggcgg gatcatgtcc tcttccggtt ccctgccgct 58560
gatgaagtat gcaaacggcg gggtggctaa caaaccgcag ttggcgctgt tcggcgaagg 58620
tcgcatgaat gaggcttatg ttccactgcc agatggtcgc agcattcctg ttaccatgac 58680
gggcgacgcg cagaccacag cgggcgccgg gcagcagatc aacagcgtca tgattgagat 58740
caacgtggcg aacgacggcg gtagcaccac gaccggtaaa tcgactggct ctggtgacag 58800
cgacgacaaa ctctgggata agatggctac ccgagtgaaa ggcgttgtca tggaagtcat 58860
ggcgaacgag aaacgcccga acggcatcct gaccaaataa ggagtaagaa atggcccggc 58920
aaacattctc ttggtatccg aattgggagt ccgagaaaac cgttaagccg gaagtgaccg 58980
tcaccaagtt cggtgacggt tatgaagccc gccaagcggc gggcctcaac ttccgcaagc 59040
aggtgtggga cgttaccttt gaaggcaacg acacgctgat taacgccatc gacgcattcc 59100
tgactgcccg gggcgccgtg gagtctttct actggacgac gccaaagaac gaaacactga 59160
tctttgtgtg tgacgagtgg cgcgttaaac gtgtcatggg ttatcgccag ttaactggca 59220
cattccgaca agtatttgag gtgtaataat ggccacgcca attcgtgctg agattcagtc 59280
gctatcacct tcggcgatga tcgaactgtt tgtcctggat atgaccggaa cctacagcgg 59340
tgggcttctg tatttccacg ctggcacaaa cggtcttaac cagaaagtag tgtggcaggg 59400
taaaacatac gatccttggc caatctcggc caagggtttc gacatgacga cccaggggac 59460
gctcccgcag ccgcaaatca ccatcgctaa catcgggggt gtgttatcgg gtgaggtgca 59520
agcaaacgac gacctcgttg gctgcaaaat cacgcgaaag agaacgctgg caaaatacct 59580
cgacgcggtg aacttcccag gcggggttaa cccggacgca gatccgaacc agtatctgcc 59640
ggatgaaatg tggtatgtgg agcagaaaac ctccgagaca cgccacagca tcgagtttaa 59700
actgtcctcc gtgtttgacc tgatggggat tcagttgcca taccgtcagg tgatccagaa 59760
ctcatgccct tggcgttacc gtggcgctga gtgcggatat accggcccgt atttcgaccg 59820
cttcgaccag ccgaccagca actcgaacga cgatgcgtgt gccaagctgc tttcatcctg 59880
caaagcccgg caagcatatt tcagcggcca gattttgcca tttgggggat tcccaggagc 59940
tacccgttat gcgaaatact cttaaaccaa cgtcagccat gatcaccgaa atccagaagc 60000
acgccattaa agcgttcccg catgaggcgt gcggagtgat tgtgaaaaag ggcaaaagca 60060
agatgcaggt tgtctcctgc cgcaacattg cggagatgcc agagcacttc ttcgtgtgtc 60120
acccggacga cctggccgct gccgaggagc agggtgagtt cgttgcggta tggcatagcc 60180
acacgcacac cgataatacc gcctcagacg ccgatatggc gggttgtgaa gcgacagggc 60240
taccttggct cattattgcg ctgcggcagg ctgacgaagc gattgagggc gtaaattggc 60300
atgtgtcaga cctgaatgtg atcactccgt cagggtttga aatgccatac ctggagcgcc 60360
cgtatgtgtt tggggttttc gactgctggt tgctgtgccg ggattacctg aaacgcgaat 60420
ttaacgttca cctggacgtg ctcccggaac tccacatccc gcgctggtgg gaaggtgacg 60480
tggacattct cggcgacaac tacaaagatc aggggctggt gcgcctggaa gaaggcacgg 60540
aaccgcagaa aggcgacatt ttcttcatgc agttcggcgg taaattcgcc aaccactgtg 60600
cggtttacat tggggatgat atgattctcc atcatcagca ggatagatta tcctgtcgcg 60660
ccatctatgg cgggtcattc gccaagcaca cgacgcacca cctacgacac aaagatctca 60720
tgtgaggctg atatgaccgc tttagctacc gtcacgctca atggggcgtt aggcaagaag 60780
tttggccgca agtggcaact tgcggttgag agcgtcaccg aggcgctgca acttatcgaa 60840
gcgaacaagc ccggcgtcaa cgcctggatg cgtgccaata tggccaagtt cgaccgctat 60900
cacattaaag tggagcgcca tgacggttcc gtttccgaag tcagtcagca ggaactctgc 60960
atgacctcgg cgggcctgaa atcaatcacg atcacaccgg taattgcagg ggcgggcgcc 61020
gcgctgcgta tcgttgtggg tgtcgtgttt atggttgcgg caatctggct cgggccggca 61080
tcgttcgcct ttggtgcgtc attagcgctg ggtggtatca tcgaactgtt atcaccgacg 61140
ccaaagatgg ccagtggcaa taagcgcagc gataacacgt cctactattt tgatggccct 61200
gttaacacgg ttgatcaggg tgttccggtg ccgctgattt acggccgtat tctggcaggc 61260
tcgcaggtaa tcagcgcgag agtgaccatt gaccagttga tgtgaggata aaatgatcaa 61320
cgacgagcac aaattcattg ccggtgcggg cggcggtggc aagagtggta gcagttctgg 61380
ccacaccgcc acggaagatc ccgatactct acaatcccga gcgatggtgt ccgtgctcga 61440
cttgatcggc gaagggcaaa tcggcgggct ggtagacggg gccaaatcag tgttcctggg 61500
cgacttgccg ctcatgaact ctgacgccac ctacaacttc aagggtgtct cctgggagat 61560
gcgcaacggc acacaagacc agacgccaat taaaggcttc aacggggtcg aaacgccgta 61620
taacgccaac acccaaatca agaacacctc gccattcacg ttcgctattt ccaacccgaa 61680
cgcggatcag gttcgctgca tcatgacact gccggcgctg accagcaccg actccaaaac 61740
gggcgatacg cacggcgccg aagtgcagta taagttccag atcagcaaca acggcagcgg 61800
gttcaccgac attgcgcctg ttggcgaaac gacgatcatc accctgcgcg gcaagaagaa 61860
cggcaaatac caacgtgcgc acctgttcaa cctgccgaag ccgggcagca attaccagat 61920
gaaggtaatt cgcctgaccg ctgacaactc tagcaactac ctccagaacg atacctatct 61980
ggatagttac tatgagatcg tggacgcgaa attgagctac ccgaactccg tgctgttcgg 62040
catcagtatc gactccagtc agttcagcaa aatccctgac cgctcctatc tcgtcgatgg 62100
gctgtatatc cgcgtgccga ataactatga cccggcgacg ggcaactact ccggcacatg 62160
ggatggcacg ttcaaactgg cggtcagcag caacccggca tggattctgt atgacctgct 62220
cctgaacacc cgttatggcc tgggttcgtt tatcagccca agcatgatca acaagggcaa 62280
gctgtatcag attggccgct actgcgacgg tctggtgagt gatggcagaa acggccagga 62340
gcgccgcttc cagatcaaca ccgtgattgc cacccgcaac gacgcctaca aggttatcca 62400
ggacattgcc tctgcgtttc gcggcatggt gttctggggt ggcggcatgg ttaacgcgac 62460
gcaggacagt ccggctgatc cggtgcaact gttcaccaac gccaacgtcg ttgatgggct 62520
gttcacctac accggcaccg cacgtaaaga ccgccactct gtcgcgctga tcacttacaa 62580
cgacccgaac gacaactaca aacaggctat cgagtatgtg gaagatcccg acctgattca 62640
gaagttcggc gtccgcaaaa ctgagtctgt cgcgttcggc tgcacaagcc gtggccaagc 62700
gcaccgcgtc ggtcagtgga ttctctactc tgagaaagca gaaacggacg ttatctactt 62760
ctcggctggc ctggatagtg cgttcgttgt gccgggcgat atcgtgaaga ttcaagacca 62820
gtatcgtgcc gggcgtcgca tgagtggccg tctgcttgcc tgcaccgcga cgaccgcgac 62880
actggacgct ccagtcaccc tggcgccagg cgcgaacctg atctctatca tgatgcctga 62940
cggcacgttt gttgaccgca ccatcgttgg cagcgggcca atgagcacga tcacattcac 63000
cgcgccaatc accagcggtc tgccggtggc gaatgcggtg tggatcatca cgcagcccga 63060
cttaacgccg ctgctggccc gcgtcatgga agtgaagcag ggtgagaacc tcggcaccgt 63120
tgatatcgcc tgcaccgcgc acaacccgac gaagttcggc gcgattgagc aaaacctgat 63180
gctggatatt ccagaccata cggtgctcga cccgacctac tcgacgcctg agaatctggt 63240
gattgatgaa accacctatt tctcaagtcc aggcaacctc ggcaccaagc tgcacgtatc 63300
gtgggacggt aaatcgccga actacattct gtcgtggcgc cgcagtgacg tggtgagcaa 63360
ctggacggca gttcccctca aaatcactga atttgagctt gcaggggtgc tggaaggggc 63420
caaatacgat ttctctgtcg ttggtgtgtc tgtaaccgga aaagtctctg acgcgcttgt 63480
aggcacgtat acggtgctcg gctccacgaa cccgcctggc ccgccgacaa acctgacagc 63540
ggtcggcgac ttccgctccg taatcctcca gtgggccaac ccaggaaacc tggatttgga 63600
ctacatcgag gtttacgaaa acagcgtgaa cgacaacagc accgccagca tgattgctcg 63660
cgtcacaggc acgctgttca accgtggcgg tctgccgggt ctggtcaagc gctggtattg 63720
gttgaaagcg gtcaacaagc gcggcctgaa atcgcagttc aacagcaacc tggggacgga 63780
agcaacgacg ctccaggcga cgcatgatga tgtggtgaaa cagtttgtcg atagctccat 63840
gcttgtgcct gaactggtgg cgggctttga agcgaaccag gggcttgttg atcagctcca 63900
gagctacttc gataaggcgt ctgaggttga gaaagcggcg aacgaaatga aaccgcgcct 63960
ggctgttctg gaagcgtgga aggcatcggt tgacgacggc acgacgcaat acgttaccca 64020
ggagcagttg ctccaggcga agaacgaaac gcagcaggcg gtaatcgaca acatgaacgc 64080
cgtcatgacc ggcccgagtg gtgcgattgc ccgagcggtc agcagcctga aaacggagat 64140
ggacgggaag tttgcgagcc tgaaaatcac cgctgaaacg gtaaacggcc tccaatcgca 64200
atatactgtt aagatcgaca acaacggcta cgtggctggc ttcggtttag cgtccgacag 64260
ttcaacgggt gtgccgactt ctgagtttat ggtgctggca gaccgcttcg cgattgcaca 64320
gccgaaccaa ggctccgggg cgtcttatcc gttcatcgtg acgagcatca acggtgtgcc 64380
gcgcgtatcc atgaactctg cattcatcac ggagatcatt gcagcgattc tgaaatcgcc 64440
tgacaataag ttccgtatcg acttgcagaa caaactaatc tccatcgagg tgtaacatgg 64500
cccaggaacg tgcgctccaa atcacatttg tcggtgacaa atatggctac tccgacttcc 64560
cgtatgagga agtccacact gctctcgttg agggtatccg ggatcgcgtc gccccaatgc 64620
gcacgtttca ggtttactcg aactttggcc gcatccgttg cggccgtaac aacaaataca 64680
cgcccgttgc caatgatgaa ctgaaattca acggcatcgt gcgcgacgac gagtttaccg 64740
gcgaaccgct gccggaaacc gcagaggcgc tgaacaagct ggattcactg ccgatcatcg 64800
agtttcactc cgattccggt gagttacgct gctactatcc agcccgatac gcttatgcgg 64860
agccgctgac gggccgcatc tatgacgtgt tcaagagcga ttgctggagc ttatgtcgtg 64920
aatggctgat cgataaccgc ggcatccggt tgcccgccgg cacaatgcaa tacgccacgg 64980
aactgaccga gaagatgggc cgcaacttct tcatcgagat cgccaaagag caaggtttcc 65040
gtgaagtgct gatccccaaa gagggtgacg tggtggtgct gggcctggat atcttccaca 65100
cctgcatcta tctggaaggc aaccgcgtgc tgcacatgtt cccggggcgc ctgagcgcta 65160
tcgaggcgta tgacggctgg ctcgaagcca acacgcaagc cattcttcgc tacccgaccg 65220
cataaggagc agatatgagc cgccgcttaa tggctgatgg cgtaaccggt aaggtcgcca 65280
tcatgcagca gggatcgcgt gacgctttcg agaacccaaa ggacaacctc agcaaaatcc 65340
atttccactc cgatctggat tacatgggga ttgtccagca actgttcatt gccaacgtcg 65400
cattcccggc gcggcaggga agtatcgaaa ctgttgaagt gtcctcgaag ggcggtggct 65460
tcttcggtaa aggcacgaag aaaaagaaat attactaccc gcgcccacag agcgggatcg 65520
cctattacta cctgggcgac attgttggtg atctggacgg gccaatgctg ggcttccgcg 65580
atggcacgat cccgctaacg tccatcccga tttaccagaa cacgtataac tccaaaggca 65640
gcaactacca ggcgtggcgc tcggtgtcgc tggggctgga tggctccaga atcatgatga 65700
aggaaacgtg gtattcgatg ggcgctgacc tgccggcgca gtcggttaac gatatcagga 65760
tcgtgaagtt caacatgatg acaggcgcga atttgcccga caacaggacg ctctacatca 65820
cgccgcaggt gttcatcgcg tcgaagggca aactggactc gcggaaccgc tatgtgaagc 65880
gcagcccaac aggcccgtat ttcgtttact acggcaggac gatgaatagc gagaacggtg 65940
gcgggcgctg ggtgtatcca atcgtcaaca acgggcaggt gcagaacgtc tacatggaag 66000
agggcggcta tcagtccgac accgtgttct attcgccgct gccaaccggt attgccgttt 66060
gattggccgt tggctatgat aagccaacta taaggatctc attatgtctt tcttcgccgg 66120
tagcgaccga atttatatta cggacacgaa tggggctatc gtgttcgaca ccaacaacga 66180
tatcccgcat atccttgggg tgtatgaagc caacattaaa aaagtgttct atgagcggta 66240
ttacactgag cagtatttca caattggcga cctcccagac gactgcgatt tcgtgatcgt 66300
tcgggccaaa tgtgtgccat ttaacctgct gaacattccg ttcgacaaga acaacccgga 66360
agcgggcggc atgacgggcg gaacgcgcag cctgggtggc tgggaatacc tcggcagttc 66420
tggcaaccgt cagcgcgtcg attgggcggt gctggcgtca gagggtggtt ctttcttcca 66480
ggggtcgctg ccgctggaga caggacaaac gatggtctgg atgggcggcg gttattctgc 66540
gtcacaatac tgtaggcgcg tgcttcacgt ttacccggag cctgcctggg gcaataaatt 66600
agtggccatg ttccagcaaa gcgttaaatc gggatatggt gcagtgccaa gtgtcgctgc 66660
ggcgattgtg aaagatggta ggcagaaagc tgccgctgtc gatatcgacg acgatcaccc 66720
ggctgtagtt tacggccccg ccggcatccg gtgggaagtt aacctgaaag tttgggcggg 66780
caagttccgc gtttaaggat ctcaaaatgg caaagcaaaa cacgattatc cgcatggctg 66840
tagacaacct ggctggcgta acaaccttcg gcgtatcagt gaccgaagat ctcggcgtgg 66900
cagttgcgca acgcggcgta tttgatatcc gcatcccgga gaaattcgaa gggattaacg 66960
cggaagcgca ggcggcggtt gacgcattca tggaagaaca tgcaacagcg ctggggctgg 67020
cataatgtcg tggtataaag ccggtcgagt caacatcgcc aatggctcga aggtagtcac 67080
aggatgggga accaagttcc tctccacggt gcgtaatggc gatatcttct tcacgaccgc 67140
taacaaagcc gatatctacg aagtggacac ggttgatagc gatacgcaga tcacgctcgc 67200
cacgccaatg acccaggcga cggccaacat ggtggaatac tccatcatcg tgaactacaa 67260
caacacgccg aacgctacga tctcgcagca gttggcagac ctgatggcag aagtgaacca 67320
gcgcaacgac cagattcaga cctggctcgc cggcacggta acgggtggcc cggacggtaa 67380
cggctactac ccgattacgg acattgctgg taacatccag aaaatcccat gcccggcact 67440
gattcgaccg ccagaaggtc aaacggtgca gacggcagat ggcctgtatg tcatgaagaa 67500
atactcggtt gccggtggca acccgcctgg ctggtatcag tctatcgaca ttgcggaagg 67560
ctcagtccat catttggttc tgaaccagga gagttgcgag atcgtcttta agaacggcaa 67620
cgccgataag cgattcgcgc agcatatcag cctggtgatc gagcagggag ttggctcaag 67680
catcatcgac ccgtggccaa ccaacatccg gtggaatcag tcgcgtaaac cgatcttgtc 67740
gtatgccaaa ggcgcgaaag atctgttcga cttcttctcg gtggacggtg gcgctacgtg 67800
gatgggcttc tttagcggca cacaaattcc acaataagga ttcgaaatgg cactccactg 67860
tttcagcggg gcgcacgcac tgaatatgag cgtagccaac gtggactcga ttctcgttgg 67920
cttccagaac ttcctggatc gccatactgg tgacgtgagc gatgccggcg acggcgttta 67980
ctgcattaac actgccgacg ttctgatgaa caacctccac tatgaggtgg cgttgtcggg 68040
ctacatgcct aacggcacat cgacgacgga gggccagtcg cttctgatcc tgggttatct 68100
ccacctgtat cgcgcattca ccaagcgcgg ggtggagaac aactatctgg atcaggcaaa 68160
gcggttcatg aatgcctacc tgacctattt ctaccgtgac acgcccattc ccaaccaggc 68220
gcaggtctgg cgctgccatt gggctatcaa cggcaagatg ccgttccgca ccttcgggcc 68280
agtgaacttc caagacccgt cagcgtccgg ggcctgggat gtgcctgtcc agttcaacgg 68340
cggcgtcggg tatgtgccag ccggttcacc gtattacggc gagcaggtga cgcgcgtcta 68400
taacgtgtat gacggcaaga tgaattggga caacgttatg gccacgccga agggcggtcg 68460
cggaacgtat gaaatgaact tctttgtgga cgaccgcaag atgcgcatga catacgacgg 68520
cgacgagctt gacgatggcc cgcaaacgac atacccaacg cgctacatcc agttgaaaga 68580
ccggacgttc actggtgtgc tgaatatctc gttcgcctgt cgctcgggcc acatcatcga 68640
ccgaaatcac ccgttcgaag gctggccaat gtggcagcac gttgagaaag cctattacgg 68700
taactcgggc gactccgaag agtggttctg cgaagcgctc tggatgatgt tcaacatcac 68760
caaagagcag aagtatctcc gcgcattcaa cgcctgcgcc tacacgctct ggaacatggc 68820
caacctgccg tcgcaaagcg tcatgttcat ccgtgacacg atgcacagca cctatacgcc 68880
attcaccgaa gggatctcct attggtggaa cgtctgcaaa aacgctgatg cgctctgcgt 68940
ccgtaacccg agcgacgggt atatccgtat cgagaaaaca gaggaactgt ttatcgagga 69000
taactcgcag gtggcgattg agcagatggc actgatcaac aaggtgaacc aggatagcta 69060
catctccatg cagatgggga tcaacagcga cccgaacatc gcgccgatgg ccaagatgaa 69120
catcttctgc cgcgtgtccg acagtctggt gcctgaaacc ggtcgcgtgt ggcgtcaccc 69180
tgtctggtcg aataacaacg tcaatccagt ggtgagccag tattacttcc gcaacatggt 69240
tgcgcaggac gacggcgccg gcaacgaata cgtcatgatg aacgggcaaa ctttcgtgcc 69300
gtatggtcag gcaacgagtg acactcacat cgaatatggc gtcctgggtg atagccgccg 69360
caacgactac tgcgggaagg tgacagtgcc aaatggctcg tccggtgttg tgctgggcct 69420
ctggggtgca gacccaacaa cacgcccgct gaaatccatc acctacaaat acctgaccaa 69480
cactcgcctg gcgatgtatg tgcgcgacgc gaacaactgg aaatggcagt tcattctgcc 69540
gggtaacggg aatggtgact ggcgcacagt gacgatccct tggggaagca tgacgctgat 69600
ggccaaccag gacaacaccg gcccgcgccc gtctacgccg gcagtcaata acgcgctaac 69660
tcaggttcag atcggcctgc ccgacggcga cccggatgca gtaggcagca tcgtgcttta 69720
ctgtttcaac gatgtgccgc ctatcttctc tggttggggc tacatgaact ggttcaagtt 69780
catgatcgtg gatcactacg actttgtgtg caacatcggc aacatctccg tggagaacac 69840
cctggagctt cgcgccaaat acacaccagg cgtgatcccg ttctccacga actacagcca 69900
gaaaaagggc aaggtggagt tctaccgcgg cacgccatac accggctacg tctatccggt 69960
ctgtttcctg attcaaggta aactggatgc cgtgcagaac tgcgtggatt acttctacga 70020
cgcgcagcag gactactaca acaagaaggg catctggggg ccgatggcac cggtatacgt 70080
ctggccacgt tgggataacg tgaactacgg ggcgccggag acattcgttt acgtcgaatg 70140
gggctatcac cagccgtggg ctggctacta cagccgagcg ctgttctcag cgtgccacct 70200
ctgggaagaa atgaagaaga tgaacctgcc tatctcgccg aagctgatca cggtatgcga 70260
aaggtggatg acatatctgg ccgacttcat ggacaagaac gacgacaaca cgccgacggt 70320
ctttcctgta gacggtttgc cctataatga tggctacgac cctgacccga atatcagttc 70380
gcctgaccat acgggccaca tgaccgcgca cttcctctgt tcagcgatca tgatgaagaa 70440
cgccggcagc acgcatccga agctcgaccg tatcattgaa ggctgcgtcc gtgagtttga 70500
gcgcacctat tacgtgtcgc agggcagaac ggagcacatg agcggcgcgt atacgtcctg 70560
ggctggcggc aactacttct acggcttctg ggctggcgaa atcatgcgag cgttcggcat 70620
gttgctggag tatcgcgaca agcagaacct gatgcctatc acggtcgtgg aagatgattt 70680
gtggcgtatc gggttggaag atggctcaac actgatcact caggatggtg gagagttcat 70740
gtatgataac cctgtttact ttgactcaat ggtgctgccg ctgctcatgc aggatggcgt 70800
cagccaaatc atgctggaag atggcgtagg cttcctttgc accgaaccgg aataacggag 70860
acacaaaatg gcagttaaca agaagattag cgatctggac accgcttcga gcattgacgg 70920
ctcggagatg atccctgtcg ttaaaggcgg cagcaacttc aaaatcctga tcagccagat 70980
taaaagctgg ttcggtgtgg catcatctgc gaacgatggc ctgatggcgg caaccgataa 71040
ggtgaaactg gccggcattc agaccaacgc cacgcaaaac gccactgatg cgcagttgcg 71100
cgaccgttca acgcataccg gtatgcaggc ggcaagcacc atcactggcc tgaaaccggt 71160
ggcgacttcc ggggtatacg ccgacttaac aggtaagcct gacctgtcgg tgactgccct 71220
tggcgccgcg ccagcgagcc acgttggtaa gggtggggtg agcgagcacc cgattgccac 71280
cgtggacacc gccggcttca tgtcgccggc aaccgtcgaa ctgctggaga gcaccaaagc 71340
cattgcgttc accgccgact acggcgatct gctgaacggc ccctggaacc gtattgcgcc 71400
gcaaggtttc gcctggtggc cggacagcaa cacggacaag ggcagcaccc acaacgacta 71460
caactcgttc ggcaccggcg tgtatcatgg cctggccgca accggcaaca agtataagga 71520
cgcgagcgag tatcacgcat tcacctcggc cgcatccact tactctatcg ccggcattcg 71580
ttcagcgagc gctatcgtga agaagggcaa ctctgcctat caaggtggct tcctgtttga 71640
agcgattgtg cattggacgc accttgctgg cacctgtatg gtgatcggcc tgacgactga 71700
cccggacaaa gcctacggca actggtcggg cagtgatgaa gggatcgcaa tcggttggaa 71760
cgccagcgac gtagcgacaa ccaccatcaa agcgatggcg ggtaacggca cgtccaccac 71820
tcgatacaac gcgacggccg gcactatcgc agacgacgcc acctatgcga ttcgcatcga 71880
agtggcccca ccggctaaag gcgtcactga cgcagtgcgt gaggcgattg tgacggtgat 71940
caacctcgat actggagtga aaatcatcga cgggatcacc atcccggatg ccgaactgcc 72000
gcgcggcgac acgccactgt atgcgatggt ggcttacggc acgctgacca acgcgaccgc 72060
tattgcagtg gatgttttgg cgattagctg cgagcgttac cgcggattct aatcaccttg 72120
ccagtcaagc agcccgcagg ctacaatttc cccattattt tctggtggag gattaaatcg 72180
tgcgggctgc tttttttgat ttaaccatcg agcagggcgc gactttccgc caagtgttcc 72240
ggtggcaaga caaatccaaa caaccttttg acctgactgg ctatacggcc aagctcatgt 72300
tgcgtcaaag cgttgcctct ccatctaccc tgaaaaccct gacaaccgag aacggcggga 72360
tcgtgctggg cggctcaaca ggcagcatca ccctgtatat gtcgccggcg gatacggccg 72420
cattacgttg ggacactgcc gtttatgatc tggcactcta cgcacctggc ggcgacgttt 72480
accgattggt ggagggttcg gctaacgtta aaccggcggt gacacgatga acgatgataa 72540
agtcattatc ctggtggttg agcaaacgcc atcaaacgtc gtgtcagtgg agggcggcac 72600
caccgttatc tccacagtcg ataccccatc tgttttaatc gctgccgaac aaggcccggc 72660
aggtattcag ggattgcccg gcccggcagc gggaaccgca tttacccgtc cagcagcagc 72720
gaatgtgtcc ggtggcaaag ccgtgacgct caatgccgca gggcaatgtc tccacgccaa 72780
cggtgcaaac gcatcaatgg caaacagcgt cgcgggaatc tcgttaaatg gcggggcgcc 72840
cggggcggat atcaccatca tcaccagtgg cggtgagatc gaggaatcag tctggaactg 72900
gcaggcgaat aagcctatct ttctggggac ggatggggcg cttactcagg tcgcgccgac 72960
ctccggttac attctggtcg tcggggtggc tgttgggcct acccgaatgc tggtaaaagt 73020
ccaacaacca atcttcattg cataggggta atacgaaatg gctcagaaat tcctgaccca 73080
aagcggcggc gttctccagg agaacctgcc taccacaact tccgccggcg cgggtgacgc 73140
gggcaagatc ccggggctgg actctaccgg tcgtctggat atgtccatga tgccaactgg 73200
cctgggcgct catactcagg tgatcactgc gagcgaagca ctgtcagcag gcgcgttcgt 73260
gaacatctac gacaacggcg gcagcttcgc cgtgcgtaac gcagatgcag cgacgggcaa 73320
acgcgctcat ggcttcgtta tctcagcggt gacgagtggt ggccaggcga ctgtctaccc 73380
ggacggcctg aacactgcac tgaccggact gacggcgggc gattactacc tgtccgatag 73440
cgcggtgggt gccgtgacca aaaccgttcc aaccggcact ggcaaaatgg ttcaacgtct 73500
gggcgcctct atgaacgcca cgactctgaa ctgcgatctc ggtcagccga ttatcctggc 73560
ataacggaga gggatcatgg ctaatagacg cccgctggcg ctggtagtcg gcaccgacca 73620
attacagcaa attccggcgg gcgactatgt tgaacccgcc accctcggct caggcacacc 73680
cggcagcgcc gtcgttcttc gcggcgacgc aaagtgggtg agcctggcta ttgccgctgc 73740
tggtctgcca gcactcgacc catcaaagaa aggcgcgggc gtaacgctct cgaacgccaa 73800
ccaaaccgca gtgtttaccg ccgcgcagca aaccgtcctg ggtattaccg gcatcacaac 73860
cggcaaatac tacttcgagg taacgtttgt ctccggcaca tcgtctggta acgccgcagt 73920
cggcctggtg ccgagcaacg agccattaac cggttcgcag atcggctata acgacggcgt 73980
gacaggttca atcggctgct tccagtcgtc cggtaacgtc tatcgcgacg gcagttcatc 74040
gtctgtaggc agcgcaaaca acttctccac cgcaggcaac tacctctgcg tggccgtgga 74100
tgctgatgcc cgtctggtgt ggttcaaatc aggaacgaac gcatggaacg gcaacgccgc 74160
aaataacccg gcaacgggtg tgggcgggat ctcaatcagc ggcaccggaa ccatttaccc 74220
ggcaatcggc accgacaagg tttcgaactg gctggccaac ttcggcgcgg tcaacttcaa 74280
ccagactgtg cctgtcggat tctcaccgtg ggttgccggc gctccaacaa cgcagcttat 74340
caccccaggg gatgtgagta tcgccacccc agcgaacggc gatctgctgc aatacaacgg 74400
cacctattgg gtcaacgttg cggtagcgac cgccatgagc ctgtatgcac cgaaagccag 74460
ccctgtgttc actggcacgg tcaaaatgcc cgtctacacg ctgacgacgc tgccaagcgc 74520
ctcagcaaac aaccaatgct caatcgtcgt ttcgaacgct acaggcgggc cggcgatgtg 74580
catttcaaac ggcacgaact ggattaacgt cagaactaac gcaacggtgg cttaaaatgc 74640
aacaggtaac ttatccgtat gagatcctta tccgcctcgg cagaaacggg attgtagggg 74700
cgcagtatca aacgatcacg gacattattg acgacgatgg cgtaaccgtc ctggcgtcgc 74760
gtgaggggcc ggtatctccc ctggcgctgg ccggtcaaac gggcgtgtcg ctggagtcaa 74820
tcatgggcca ggcggcatcc gtcgcgctga ctgaaaacga acaactgaaa ggcgtcaatg 74880
ctcaactggc actcctgaca cagacgctgc aacagcgcct ggatgaagcg aatgccaaat 74940
tagctgcgct cggggctgga acttctctcg ttgcctcaaa cacttccggt gagaacgttt 75000
cagaagttta aaatggcatt acaaatggcc atgaactatc atggcctcgt tacacaacct 75060
tgcaagagaa tgccaaggac aaatcatgac cacagaagaa agtagaggac tttccatgag 75120
cgaaatgaac tccctggcgg gccagatcag cgaggttaaa gaggatatgc gggaaatccg 75180
cgccagcatg agcaagattg ccgatgctgt tactcgcctt gctgttttgg aatcgcaaaa 75240
caaggcgaac gctcaacgta tggagaatct cgaagcacgt caaaccacgg ttgaaaagga 75300
atccgcggaa acccgtctgc aactcattcg agcgcaggca cagctttccg gtgcaatgac 75360
gacaatcaag atcctctgga tggtgatcgg ttcgacagca gtcacaattg gcatcaaact 75420
ctttacttag gaacaagcac ccatgaggtt cattatgatc cagctactca aagcctttca 75480
cgatgtgaga gcctacttcc taatcctccc attctgcctg cttctctggt ggactgatcc 75540
ggtcgtattt gaaacatgga ttcagtgggg cgccgcactc ccaattatcg tcggcgtaac 75600
gttggtggtt cgcaagatca tctttaacac aatcgaccta tccgaagtca ttgagcaagc 75660
ctgcaaaagc tcaacgggcg cgggtctggt atttctcggc gtggcgttct tctctgccat 75720
gttcctgatt gctgcgacgc tatggctatc ccattagccc tgcctaacga cgcgcctcaa 75780
tatgtgccag tgctgcaaca ggagatcgtt cagcactggc catccattcc gctgccgtct 75840
gttcttgccg cgcaggtcga gcaagagagc ttgtggaagg taaaggcgac gttacgcaac 75900
ccgaaaaaca ataacgagct tggcgccggc cttggccagt tcaccaagaa caacaagttc 75960
gacgccttga ccgagatcaa gacccaatac ccggcactct tcaaagagtg gtcatggaac 76020
aacccctatg acgcgcagta tcaactgcgt ggagttgtgg tgaagaaccg cgacaacttc 76080
aaccggatta agtgggctgc aactgattac gaccgcctgg ccatgatgga cagtgcctac 76140
aactcgggat atggcggttt gctgttcagg aaacgctatt gcgccaacct ccccaattgc 76200
aatcctggga agtggtttgg ccacatggaa tacgcctcca cccaaagcaa gaagccgcag 76260
gcggggtata agcagtcttt cgccgatatc acgagcaccc acgttaaaaa cgtgatgatc 76320
gtgcgtcgtc cgaaatacac gtttatggac ggtaagaaat gaaagatcgc atcagtccag 76380
tgattctcct gctggttgga atggtgctgg ggatcggcct cactttgtgg ggccagtctc 76440
ttctctcttc caaacatgag gtgaaggaag caaaagcggc agtggtcggc accggccagg 76500
ctgtcgttgc tgcaaacaaa gcggaagccg aattagccac gagcctggat aatatcgcga 76560
agaacggcgg taaaattcgg gatgcgctgg acgaccggct caacactccc tttgaactaa 76620
agagcgcatc caatggaaac attaaaagca ctaagccagc cagtaatggt gcggcgtcgg 76680
tcaatgccgc tgaatgtcca cctgcgatta ttgacggtga cagctatatg ccttttgacg 76740
ttggcactct taggttgctc aacgccgccc gcgccggaac ccctgttgat agtatcaccg 76800
tcagcgatgc agaaagcgca gcccctgcct ttgttagaat ccgaatctac gtccgaaacg 76860
acaccgaaat agccaagatg tataacgacc tggctgctcg gcataattcg ttggtagatc 76920
aggtggctgc gtatcagcac cggcagagat tgcgattagg catcaaagag tagttccaaa 76980
acccgcctgt tgtggattag gatgtatctg atccctcaac caacaggcgg gtttttatat 77040
ggccggtaaa aacagacaac ggacagccac ttcacataaa ccacagcgtc gccgtcaatt 77100
tcaggacgag ccgcgtgagt tcgagaacat tgtccctctt aacgcccaac cgtttcacaa 77160
gccccaacca atcatcgccc agaacgaagc ccagaagcgc tatatcaacg ccattcgcac 77220
ccagacgatt acctttgcgt cagggcctgc tggcgtcggt aaaacgtggc tggcgggcgc 77280
actcgcagcg gaacaactga caggacggaa aattgagaag atcattatca cgcgcccggc 77340
ggttgaagcg ggagagaaac ttggctttct tcctggagag atcgaggaga aatatgcccc 77400
atacctcgcc cccttccgtg acgtgctgga cgaacggctc ggtaaatcct tcgtagacct 77460
ggccctcaag cgcggcaaaa tcgaagcagc gccgttcgcc tatatgcgcg gccggacgtt 77520
caagaacgcg ctggtgatcc tggatgaagc ccagaacacc acgccgacgc agatgaagat 77580
gttcctgacc cgtatcggtg aaaactgcac cgtggtggtc aacggcgacc tgaaccagaa 77640
ggacattccc ggcatgtctg gttttgagga tgcgattaaa cgcctcagtt tcatcccctc 77700
aatcagtcac gtaaaattcg accatgacga cgtggtgcgt tccgacatct gtcaagaaat 77760
cgtgcaggct tacgaagagg ggcctgatcc ggtgtataac gccagataag acaaacagcg 77820
ggcttcggcc cgctttttgc ctgttgggtg atgacttggg tgatccatcc cgcaaccata 77880
attctttt 77888
Claims (8)
- 살모넬라 세텐베르그(Salmonella Senftenberg)에 특이적인 사멸능을 갖는, 서열번호 1로 표시되는 염기서열로 이루어진 박테리오파지 SS1.
- 제1항에 있어서, 상기 박테리오파지는 수탁번호 KFCC11829P인, 박테리오파지 SS1.
- 제1항의 박테리오파지 SS1을 포함하는, 항생용 조성물.
- 제1항의 박테리오파지 SS1을 포함하는, 사료 첨가용 조성물.
- 제4항의 사료 첨가용 조성물을 포함하는, 사료.
- 제1항의 박테리오파지 SS1을 포함하는, 소독제.
- 제1항의 박테리오파지 SS1을 포함하는, 세척제.
- 제1항의 박테리오파지 SS1을 인간을 제외한 개체에 투여하는 단계를 포함하는, 살모넬라 세텐베르그에 의한 감염성 질병의 예방 또는 치료 방법.
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KR20110134554A (ko) * | 2010-06-09 | 2011-12-15 | 주식회사 인트론바이오테크놀로지 | 살모넬라 콜레라수이스 또는 살모넬라 두블린 감염을 방지 및 처치하는 방법 |
KR20130028275A (ko) * | 2011-09-09 | 2013-03-19 | 주식회사 인트론바이오테크놀로지 | 살모넬라 티피무륨 감염을 방지 및 처치하는 방법 |
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KR20110134554A (ko) * | 2010-06-09 | 2011-12-15 | 주식회사 인트론바이오테크놀로지 | 살모넬라 콜레라수이스 또는 살모넬라 두블린 감염을 방지 및 처치하는 방법 |
KR20130028275A (ko) * | 2011-09-09 | 2013-03-19 | 주식회사 인트론바이오테크놀로지 | 살모넬라 티피무륨 감염을 방지 및 처치하는 방법 |
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CN114231499A (zh) * | 2021-11-18 | 2022-03-25 | 青岛嘉智生物技术有限公司 | 噬菌体及其应用 |
CN114231499B (zh) * | 2021-11-18 | 2024-05-17 | 青岛嘉智生物技术有限公司 | 噬菌体及其应用 |
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