KR20220013556A - 인간 만능 줄기 세포로부터 미세아교세포의 신속하고 결정적인 생성 - Google Patents

인간 만능 줄기 세포로부터 미세아교세포의 신속하고 결정적인 생성 Download PDF

Info

Publication number
KR20220013556A
KR20220013556A KR1020217040483A KR20217040483A KR20220013556A KR 20220013556 A KR20220013556 A KR 20220013556A KR 1020217040483 A KR1020217040483 A KR 1020217040483A KR 20217040483 A KR20217040483 A KR 20217040483A KR 20220013556 A KR20220013556 A KR 20220013556A
Authority
KR
South Korea
Prior art keywords
seq
site
microglia
chromosome
leu
Prior art date
Application number
KR1020217040483A
Other languages
English (en)
Inventor
마티아스 파브로브스키
아나 마르티나 스파이셔
Original Assignee
베스트푈리셰 빌헴스 우니베지태트 뮌스터
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by 베스트푈리셰 빌헴스 우니베지태트 뮌스터 filed Critical 베스트푈리셰 빌헴스 우니베지태트 뮌스터
Publication of KR20220013556A publication Critical patent/KR20220013556A/ko

Links

Images

Classifications

    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
    • C12N5/06—Animal cells or tissues; Human cells or tissues
    • C12N5/0602—Vertebrate cells
    • C12N5/0618—Cells of the nervous system
    • C12N5/0622—Glial cells, e.g. astrocytes, oligodendrocytes; Schwann cells
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/87—Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation
    • C12N15/90—Stable introduction of foreign DNA into chromosome
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
    • A61K35/28—Bone marrow; Haematopoietic stem cells; Mesenchymal stem cells of any origin, e.g. adipose-derived stem cells
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
    • A61K35/30—Nerves; Brain; Eyes; Corneal cells; Cerebrospinal fluid; Neuronal stem cells; Neuronal precursor cells; Glial cells; Oligodendrocytes; Schwann cells; Astroglia; Astrocytes; Choroid plexus; Spinal cord tissue
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
    • A61K35/48—Reproductive organs
    • A61K35/54—Ovaries; Ova; Ovules; Embryos; Foetal cells; Germ cells
    • A61K35/545—Embryonic stem cells; Pluripotent stem cells; Induced pluripotent stem cells; Uncharacterised stem cells
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/52—Cytokines; Lymphokines; Interferons
    • C07K14/53—Colony-stimulating factor [CSF]
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/52—Cytokines; Lymphokines; Interferons
    • C07K14/54—Interleukins [IL]
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2501/00—Active agents used in cell culture processes, e.g. differentation
    • C12N2501/10—Growth factors
    • C12N2501/113—Acidic fibroblast growth factor (aFGF, FGF-1)
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2501/00—Active agents used in cell culture processes, e.g. differentation
    • C12N2501/10—Growth factors
    • C12N2501/115—Basic fibroblast growth factor (bFGF, FGF-2)
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2501/00—Active agents used in cell culture processes, e.g. differentation
    • C12N2501/10—Growth factors
    • C12N2501/125—Stem cell factor [SCF], c-kit ligand [KL]
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2501/00—Active agents used in cell culture processes, e.g. differentation
    • C12N2501/10—Growth factors
    • C12N2501/15—Transforming growth factor beta (TGF-β)
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2501/00—Active agents used in cell culture processes, e.g. differentation
    • C12N2501/10—Growth factors
    • C12N2501/155—Bone morphogenic proteins [BMP]; Osteogenins; Osteogenic factor; Bone inducing factor
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2501/00—Active agents used in cell culture processes, e.g. differentation
    • C12N2501/10—Growth factors
    • C12N2501/16—Activin; Inhibin; Mullerian inhibiting substance
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2501/00—Active agents used in cell culture processes, e.g. differentation
    • C12N2501/10—Growth factors
    • C12N2501/165—Vascular endothelial growth factor [VEGF]
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2501/00—Active agents used in cell culture processes, e.g. differentation
    • C12N2501/20—Cytokines; Chemokines
    • C12N2501/21—Chemokines, e.g. MIP-1, MIP-2, RANTES, MCP, PF-4
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2501/00—Active agents used in cell culture processes, e.g. differentation
    • C12N2501/20—Cytokines; Chemokines
    • C12N2501/22—Colony stimulating factors (G-CSF, GM-CSF)
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2501/00—Active agents used in cell culture processes, e.g. differentation
    • C12N2501/20—Cytokines; Chemokines
    • C12N2501/23—Interleukins [IL]
    • C12N2501/2303—Interleukin-3 (IL-3)
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2501/00—Active agents used in cell culture processes, e.g. differentation
    • C12N2501/20—Cytokines; Chemokines
    • C12N2501/23—Interleukins [IL]
    • C12N2501/2306—Interleukin-6 (IL-6)
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2501/00—Active agents used in cell culture processes, e.g. differentation
    • C12N2501/20—Cytokines; Chemokines
    • C12N2501/23—Interleukins [IL]
    • C12N2501/2334—Interleukin-34 (IL-34)
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2501/00—Active agents used in cell culture processes, e.g. differentation
    • C12N2501/50—Cell markers; Cell surface determinants
    • C12N2501/599—Cell markers; Cell surface determinants with CD designations not provided for elsewhere
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2501/00—Active agents used in cell culture processes, e.g. differentation
    • C12N2501/60—Transcription factors
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2501/00—Active agents used in cell culture processes, e.g. differentation
    • C12N2501/70—Enzymes
    • C12N2501/72—Transferases (EC 2.)
    • C12N2501/727—Kinases (EC 2.7.)
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2502/00—Coculture with; Conditioned medium produced by
    • C12N2502/08—Coculture with; Conditioned medium produced by cells of the nervous system
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2506/00—Differentiation of animal cells from one lineage to another; Differentiation of pluripotent cells
    • C12N2506/45—Differentiation of animal cells from one lineage to another; Differentiation of pluripotent cells from artificially induced pluripotent stem cells
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2510/00—Genetically modified cells
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2513/00—3D culture
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2533/00—Supports or coatings for cell culture, characterised by material
    • C12N2533/50—Proteins
    • C12N2533/54—Collagen; Gelatin
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2830/00—Vector systems having a special element relevant for transcription
    • C12N2830/001—Vector systems having a special element relevant for transcription controllable enhancer/promoter combination
    • C12N2830/002—Vector systems having a special element relevant for transcription controllable enhancer/promoter combination inducible enhancer/promoter combination, e.g. hypoxia, iron, transcription factor
    • C12N2830/003—Vector systems having a special element relevant for transcription controllable enhancer/promoter combination inducible enhancer/promoter combination, e.g. hypoxia, iron, transcription factor tet inducible

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Chemical & Material Sciences (AREA)
  • Zoology (AREA)
  • Genetics & Genomics (AREA)
  • Organic Chemistry (AREA)
  • Biotechnology (AREA)
  • Cell Biology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Health & Medical Sciences (AREA)
  • Developmental Biology & Embryology (AREA)
  • Neurosurgery (AREA)
  • Neurology (AREA)
  • Wood Science & Technology (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Biochemistry (AREA)
  • General Engineering & Computer Science (AREA)
  • Immunology (AREA)
  • Microbiology (AREA)
  • Molecular Biology (AREA)
  • Epidemiology (AREA)
  • Virology (AREA)
  • Biophysics (AREA)
  • Reproductive Health (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Ophthalmology & Optometry (AREA)
  • Toxicology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Hospice & Palliative Care (AREA)
  • Psychiatry (AREA)
  • Mycology (AREA)

Abstract

본 발명은 a) 전사 조절인자 단백질을 코딩하는 뉴클레오티드 서열의 제1 게놈성 안전한 하버 부위로의 표적화된 삽입 단계; 및 b) 전사 인자 PU.1의 코딩 서열(서열번호: 1)의 제2 게놈성 안전한 하버 부위로의 표적화된 삽입 단계로서, 여기서 유전자는 전사 조절인자 단백질에 의해 조절되는, 유도성 프로모터에 작동가능하게 연결되는 단계; PU.1(서열번호: 2)의 발현 단계; 및 단계 a) 및 b)로부터 받은 줄기 세포를 미세아교세포의 배아 발달 또는 성체 미세아교세포 증식, 분화 또는 분극화 중 적어도 한 단계 동안 신호전달을 모방하는 적어도 하나의 성장 인자 또는 소분자에 노출시키면서 배양하는 단계를 포함하는, 줄기세포로부터 미세아교세포를 생산하는 방법에 관한 것이다. 추가로, 본 발명은 본 발명의 방법에 의해 수득된 미세아교세포 및 이의 다양한 용도에 관한 것이다.

Description

인간 만능 줄기 세포로부터 미세아교세포의 신속하고 결정적인 생성
본 발명은 줄기세포로부터 미세아교세포(microglia)를 생산하는 방법으로서, 전사 조절인자 단백질(transcriptional regulator protein)을 코딩(encoding)하는 뉴클레오티드 서열의 제1 게놈성 안전한 하버 부위(genomic safe harbour site)로의 표적화된 삽입(targeted insertion) 단계; 및 전사 인자(transcription factor) PU.1의 코딩 서열의 제2 게놈성 안전한 하버 부위로의 표적화된 삽입 단계로서, 여기서 유전자는 전사 조절인자 단백질에 의해 조절되는, 유도성 프로모터(inducible promoter)에 작동가능하게 연결되는 단계; PU.1의 발현 단계; 및 단계 a) 및 b)로부터 받은 줄기 세포를 미세아교세포의 배아 발달 또는 성체 미세아교세포 증식, 분화 또는 분극화(polarization) 중 적어도 한 단계 동안 신호전달(signaling)을 재연하는(recapitulate) 적어도 하나의 성장 인자 또는 소분자에 노출시키면서 배양하는 단계를 포함하는, 줄기세포로부터 미세아교세포를 생산하는 방법에 관한 것이다. 추가로, 본 발명은 본 발명의 방법에 의해 수득된 미세아교세포 및 이의 다양한 용도에 관한 것이다.
미세아교세포는 중추신경계(CNS)에 있는 상주 면역 세포이다 [Schafer et al., 2015]. 이들은 초기 배아 발달에서 원시 조혈의 첫 번째 급증(wave) 동안 발생하는 초기 난황낭 대식세포에서 유래한다. 원시 난황낭 대식세포는 발달 중인 CNS를 거주시키기 위해 순환계가 확립되자마자 혈류를 통해 퍼진다. 다른 기관의 조직-상주 대식세포와 달리, 미세아교세포는 배아 발달의 후기 단계 동안 태아 단핵구에 의해 대체되지 않는다 [McGrath et al., 303; Ginhoux et al., 2010; Gomez Perdiguero et al., 2015]. 초기 배아 발달 동안 미세아교세포 집단을 확립한 후, 미세아교세포는 골수-유래 세포에 의해 대체되는 것이 아니라, 국부적 증식에 의해 일생 동안 자체-유지된다 [R
Figure pct00001
u et al., 2017]]. 미세아교세포는 뇌와 척수 전체에 걸쳐 균일하게 분포되어 있으며 CNS의 발달, 유지, 가소성 및 방어에서 중대한 역할을 한다 [Schafer et al., 2015]. 건강한 CNS에서 "휴면하고 있는" 항상성 미세아교세포는 작은 세포체 및 미세한 세포 과정을 가진 고도로 분기된 세포이다. 이들 미세아교세포 과정은 운동성이 있고 지속적으로 이의 환경을 샘플링하여 내부 또는 외부 위험의 신호(예컨대 병원체 침입 또는 손상되거나 죽어가는 세포에 의해 국부적으로 생성된 신호)를 스캔한다. 이러한 신호의 검출은 미세아교세포의 형태, 유전자 발현, 및 기능의 엄청난 변화를 포함하는, 미세아교세포 활성화를 야기한다. 활성화 직후, 미세아교세포는 이의 과정을 철회하고 아메바-유사 외관으로 되돌아간다. 그들은 화학주성 구배에 따라 CNS 병변으로 활발히 이동하고 염증성 시토카인을 분비한다.
신경전달물질 및 시토카인 수용체를 포함한, 세포 표면 수용체의 큰 레퍼토리를 통해, 그들은 뉴런, 다른 신경교 세포, 및 말초 면역계 세포와 소통한다 [Kettenmann et al., 2011]. 이의 다양한 기능 및 건강한 CNS에서 면역계의 대표로서 이의 고유한 위치에 비추어, 미세아교세포가 많은 신경 질환의 발병 및 진행에 연루되어 있다는 것은 놀라운 일이 아니다 [Ransohoff et al., 2016].
가장 최근에, 알츠하이머병(AD) 및 노화, 근위축성 측삭 경화증(amyotrophic lateral sclerosis) 또는 타우병증-관련 전두측두엽 변성(tauopathy-related frontotemporal lobar degeneration)(FTLD-tau)을 포함한 기타 신경퇴행성 질환(neurodegenerative disease)의 마우스 모델에서 미세아교세포의 단일 세포 전사체적 프로파일링(single cell transcriptomic profiling)은, 미세아교세포 신경퇴행성 표현형(MGnD) [Krasemann et al., 2017] 또는 질환-연관 미세아교세포(DAM) [Keren-Saul et al., 2017]라고 칭해지는 미세아교세포의 작은 서브세트에서 염증유발성(pro-inflammatory) 전사체적 시그니처(signature)를 밝혀냈다. 항상성으로부터 질환-연관 표현형으로의 미세아교세포 전환(switch)은 신경퇴행성에서 변경된 뇌 항상성에 대한 반응으로 발생하는 것으로 생각되며 고유한 시간적 및 공간적으로 제어되는 전사 프로그램에 의존한다 [Krasemann et al., 2017; Keren-Shaul et al., 2017; Butovsky et al., 1998]. 대부분의 경우에, 이들 세포가 보호 기능을 갖는지 질환-유발/ 전파 기능을 갖는지는 여전히 불분명하다. 시험관내 및 생체내, 건강 및 질환에서 인간 미세아교세포에 대한 접근은 유익한 기능과 유해한 기능 둘 다와 연관된 인자의 확인 및 항상성 미세아교세포 시그니처를 복원하거나 DAM 미세아교세포 시그니처를 유도하는 전략의 개발을 용이하게 할 것이다. 이는 우리가 신경퇴행성 질환의 치료를 위해 미세아교세포를 표적화할 수 있게 할 것이다.
많은 인간 세포 유형의 단리 또는 시험관내 유도는 여전히 도전과제이고 비효율적이다. 특히 미세아교세포를 포함한 인간 CNS의 세포는, 수득하기가 특히 어렵다. 과거에는, 신경외과 표본 또는 사후 뇌 조직으로부터 저효율 단리가 유일한 접근 경로를 나타냈다. 인간 만능 줄기 세포(Human pluripotent stem cell)(hPSC)는, 이론상, 인간 유기체의 모든 세포 유형이 생산될 수 있는 무한하고 재생 가능한 공급원을 나타낸다 [Thomson et al., 1998]. 인간 피부 섬유모세포가 배아 줄기 세포와 동일한 특성을 나타내는 인간 유도 만능 줄기 세포(human induced pluripotent stem cell)(hiPSC)로 쉽게 전환될 수 있다는 획기적인 발견은, 재생 의학에서 적용을 위한 자가 및 맞춤형 세포 유형을 생성할 수 있게 한다. 질환 모델링, 약물 발견, 및 세포 이식을 포함한 몇몇 주요 적용의 경우, hPSC로부터 성숙한 인간 세포 유형의 대규모 제조가 필요하다. 최근에, 미세아교세포의 생성을 위한 최초의 hPSC-분화 프로토콜이 공개되었다. 이는 인터루킨(IL)-34 및 콜로니-자극 인자 1(CSF-1)이 보충된 동일한 "인간 뇌척수액의 성분 농도와 일치하도록 조정된 신경아교 분화 배지"에서 수개월 동안 배양된 배상체(embryoid body)(EB)의 초기 형성을 기반으로 하였다 [Muffat et al., 2016]. 이 중대한 간행물은 인간 미세아교세포의 최종 성숙 및 유지를 위한 정교한 배지 조성을 제공하였다. 그러나, 프로토콜의 긴 지속기간, 분화의 잘못 정의된 초기 단계(즉, EB-기반, 배아 근거를 거의 따르지 않는 중간 단계), 및 세포 정제를 위한 몇몇 기계적 조작 단계의 필요성은 이 프로토콜의 광범위한 적용을 금지할 가능성이 있다. 그 후에, 몇몇 다른 그룹이 유사하지만 상이한 통상적인 분화 접근법에 의해 hPSC로부터 미세아교세포-유사 세포의 생성을 입증하였다 [Abud et al., 2017; Takata et al., 2017; Haenseler et al., 2017; Pandya et al., 2017; Douvaras et al., 2017]. 그럼에도 불구하고, 하류 적용에 필요한 양 및 순도에서, 미세아교세포를 포함한 특정 인간 세포 유형의 시험관내 유도는 여전히 도전과제이며, 현재 대체 방법이 모색되고 있다 [Cohen et al., 2011]. 통상적인 분화와 비교한 보다 최근의 제조 전략은 직접적인 세포 리프로그래밍이다 [Ladewig et al., 2013]. 이는 만능 중간체를 통한 진행 없이 임의의 세포 유형(전형적으로 피부 섬유모세포)이 또 다른 유형으로 직접 전환되는 것을 지칭한다. 쉽게 접근할 수 있는 세포 유형으로부터 세포를 생산하기 위한 빠른 경로를 제공하긴 하지만, 원하는 세포 집단의 수율 및 순도는 여전히 낮고 불충분하다 [Zhang et al., 2013]. 최근에, "정방향 프로그래밍(forward programming)"으로 칭해지는 제3의 경로가, 전례 없는 속도 및 효율성으로 성숙한 인간 세포 유형의 제조를 위해 제안되었다 [Zhang et al., 2013].
hPSC를 포함한 만능 줄기 세포를 성숙한 세포 유형으로 직접 전환시키는 방법으로서의 정방향 프로그래핑은, 인간 세포의 유도를 위한 강력한 전략으로 인식되어 왔다. 이는 줄기 세포를 특정 성숙한 세포 유형으로 전환하기 위해, 주요 계통 전사 인자(또는 IncRNA 및 microRNA를 포함하는 비-코딩(non-coding) RNA)의 강제 발현을 포함한다. 현재 이용가능한 정방향 프로그래밍 프로토콜은 주로 세포의 렌티바이러스 형질도입을 기반으로 하며, 이는 무작위로 삽입된 유도성 카세트의 변화가 많은 발현 또는 완전한 침묵을 결과한다. 이는 필요한 전사 인자를 발현하는 하위 집단을 단리하기 위해 추가 정제 단계의 필요성을 결과한다. 따라서 이들 방법의 추가 개선이 분명히 필요하다.
언급된 방법에 대한 임의의 개선은 트랜스진(transgene)과 같은 유도성 카세트 내에 함된 유전적 물질의 안정적인 전사가 침묵 및 기타 음성 통합 부위-관련 영향에 내성이 있음을 보장하여야 한다. 침묵은 DNA 메틸화 또는 히스톤 변형을 포함한 여러 후성유전적 메커니즘에 의해 유발될 수 있다. 렌티바이러스 형질도입에 기초한 선행 기술 방법으로, 수득된 세포는 트랜스진이 완전히, 부분적으로 또는 침묵화되어 발현되는 이종 집단이다. 분명히, 이것은 많은 적용에서 바람직하지 않다. 바이러스 벡터는 이의 유전적 물질을 게놈의 전사 활성 영역에 통합하는 경향을 보여, 삽입 돌연변이유발로 인한 발암성 사건의 가능성을 증가시킨다. 많은 적용을 위해, 유도성 카세트가 필요에 따라 켜지고 높은 수준을 포함한 특정한 수준에서 전사될 수 있도록, 세포에 삽입된 유전적 물질의 전사를 제어하는 것이 바람직한다. 이것은 유도성 카세트의 삽입이 게놈에서 무작위인 경우는 달성될 수 없다.
미세아교세포가 몇몇 중증 질환에 관여하고 또한 생체 조직으로부터 이의 단리가 여전히 달성하기 힘든 방식으로 뇌 조직에 얽혀 있다는 문제는 여러 간행물에서 다루어졌다. 이 문제를 극복하기 위해, 인간 줄기 세포는 예를 들어 정의된 배양 조건 [Muffat et al., 2016] 또는 줄기 세포 유래 뉴런과의 공동 배양 [Haenseler et al., 2017; Takata et al., 2017]을 통해 미세아교세포 또는 미세아교세포-유사 세포를 생성하기 위해 사용된다. 이들 방법은 줄기 세포를 미세아교세포로 분화시키기 위해 성장 인자 및 시토카인에 대한 노출에만 의존한다.
추가로, 이들이 신경퇴행성 질환, 신경염증성(neuroinflammatory) 또는 자가면역 질환, 자가-항체-매개 뇌염(auto-antibody-mediated encephalitis) 또는 감염성 질환(infectious disease), 신경혈관 질환(neurovascular disease), 뇌졸중(stroke), 외상성 뇌 손상 및 암을 포함한 중추신경계의 거의 모든 질환에서 중요한 역할을 하기 때문에 이러한 특수 세포 유형에 대한 필요성은 크지만, 상이한 질환에서 이의 역할에 대한 정밀한 메커니즘은 여전히 불분명한다. 선행 기술은 일치하며, 줄기 세포-유래 미세아교세포는 실제로 원래 환자의 질환-표현형을 요약하고 있다 [Muffat et al., 2016; Abud et al., 2017; Takata et al., 2017]. 이러한 지식으로, 특정 질환에 대한 미세아교세포 관련의 엄청난 과학적 격차는 줄기 세포로부터 미세아교세포를 생성함으로써 극복할 수 있다. 그러나 줄기 세포를 분화하는 통상적인 프로토콜은 시간이 많이 걸리고 결과가 설득력이 없다.
따라서, 본 발명의 발명자들은 줄기 세포의 게놈 내로 유도성 카세트의 안정적인 도입을 사용하며, 동시에 그 유도성 카세트의 전사 그리고 그로 인해 삽입된 전사 인자를 제어할 수 있음으로써 줄기 세포로부터 미세아교세포를 생성하기 위한 신속한 방법을 개발하였다. 미세아교세포의 생성을 위한 리프로그래밍 인자로서 기능하는 이들 전사 인자의 가능성은 이전에 알려지지 않았으며 본 발명자의 고유한 지식을 나타낸다. 이를 통해 천연 미세아교세포 집단에서 관찰되는 모든 표면 마커 및 RNA를 발현하는 순수한 미세아교세포 집단을 생성할 수 있게 된다. 게다가 이 방법은 신경퇴행성 질환 환자의 인간 iPS 세포로부터 미세아교세포를 구별하는데 사용될 수 있으므로 달리 의학적 검사에서 여전히 완전히 불활성인 세포 집단을 분석할 수 있게 한다. 따라서, 쉽게 접근할 수 있는 공급원으로부터 성숙한 인간 미세아교세포의 제조에 대한 강한 필요성이 있다. 따라서 본 출원의 기초가 되는 기술적 문제는 이들 필요성에 부합하는 것이다. 기술적 문제는 청구범위에 반영되고, 명세서에 기재되고 하기에 주어진 실시예 및 도면에 예시된 실시양태를 제공함으로써 해결된다.
본 발명의 발명자들은 줄기 세포로부터 미세아교세포를 생산하는 방법을 개발하였다.
본 발명은 줄기 세포로부터 미세아교세포를 생산하는 방법으로서, a) 전사 조절인자 단백질을 코딩하는 뉴클레오티드 서열을 제1 게놈성 안전한 하버 부위로의 표적화된 삽입 단계; 및 b) 전사 인자 PU.1의 코딩 서열(서열번호: 1)의 제2 게놈성 안전한 하버 부위로의 표적화된 삽입 단계로서, 여기서 유전자는 전사 조절인자 단백질에 의해 조절되는, 유도성 프로모터에 작동가능하게 연결되는 단계; PU.1(서열번호: 2)의 발현 단계; 및 c) 단계 a) 및 b)로부터 받은 줄기 세포를 미세아교세포의 배아 발달 또는 성체 미세아교세포 증식, 분화 또는 분극화 중 적어도 한 단계 동안 신호전달을 재연하는 적어도 하나의 성장 인자 또는 소분자에 노출시키면서 배양하는 단계를 포함하는, 줄기세포로부터 미세아교세포를 생산하는 방법에 관한 것이다.
본 발명의 한 실시양태에서, 적어도 하나의 성장 인자 또는 소분자는 액티빈 A(서열번호: 7), BMP4(서열번호: 8), FGF(서열번호: 9), VEGF-A(서열번호: 10), LY294002, CHIR99021, SCF(서열번호: 11), IL-3(서열번호: 12), IL-6(서열번호: 13), CSF1(서열번호: 14), IL-34(서열번호: 15), CSF2(서열번호: 16), CD200(서열번호: 17), CX3CL1(서열번호: 18), TGFβ1(서열번호: 19), 및 IDE1로 이루어진 군으로부터 선택된다.
본 발명의 방법의 추가 실시양태에서, 적어도 하나의 성장 인자는 CSF1(서열번호: 14) 또는 IL-34(서열번호: 15)이다.
본 발명의 방법의 추가 실시양태에서, 적어도 하나의 소분자는 CHIR99021, LY294002 또는 IDE1이다.
본 발명의 방법의 또 다른 실시양태에서, 제1 및 제2 게놈성 안전한 하버 부위는 상이하다.
본 발명의 방법의 추가 실시양태에서, 방법은 전사 인자 CEBPB의 유전자의 코딩 서열(서열번호: 3)의 삽입 및 이의 발현을 추가로 포함한다.
본 발명의 방법의 또 다른 실시양태에서, 방법은 전사 인자 RUNX1의 유전자의 코딩 서열(서열번호: 4)의 삽입 및 이의 발현을 추가로 포함한다.
본 발명의 방법의 추가 실시양태에서, 방법은 전사 인자 IRF8의 유전자의 코딩 서열(서열번호: 5)의 삽입 및 이의 발현을 추가로 포함한다.
본 발명의 방법의 또 다른 실시양태에서, 방법은 전사 인자 SALL1의 유전자의 코딩 서열(서열번호: 6)의 삽입 및 이의 발현을 추가로 포함한다.
본 발명의 방법의 추가 실시양태에서, 전사 조절인자 단백질은 역(reverse) 테트라시클린 전사활성인자(reverse tetracycline transactivator)(rtTA)(서열번호: 20)이고 이의 활성은 독시시클린 또는 테트라시클린에 의해 제어된다.
본 발명의 방법의 또 다른 실시양태에서, 유도성 프로모터는 Tet 반응성 요소(Tet Responsive Element)(TRE)(서열번호: 21)를 포함한다.
본 발명의 방법의 추가 실시양태에서, 상기 제1 및 상기 제2 게놈성 안전한 하버 부위는 hROSA26 유전자좌(locus)(서열번호: 22), AAVS1 유전자좌(서열번호: 23), CLYBL 유전자(서열번호: 24), CCR5 유전자(서열번호: 25), HPRT 유전자(서열번호: 26) 또는 염색체 8 상의 부위 ID 325(서열번호: 27), 염색체 1 상의 부위 ID 227(서열번호: 28), 염색체 2 상의 부위 ID 229(서열번호: 29), 염색체 5 상의 부위 ID 225(서열번호: 30), 염색체 14 상의 부위 ID 259(서열번호: 31), 염색체 X 상의 부위 ID 263(서열번호: 32), 염색체 2 상의 부위 ID 303(서열번호: 33), 염색체 4 상의 부위 ID 231(서열번호: 34), 염색체 5 상의 부위 ID 315(서열번호: 35), 염색체 16 상의 부위 ID 307(서열번호: 36), 염색체 6 상의 부위 ID 285(서열번호: 37), 염색체 6 상의 부위 ID 233(서열번호: 38), 염색체 134 상의 부위 ID 311(서열번호: 39), 염색체 7 상의 부위 ID 301(서열번호: 40), 염색체 8 상의 부위 ID 293(서열번호: 41), 염색체 11 상의 부위 ID 319(서열번호: 42), 염색체 12 상의 부위 ID 329(서열번호: 43), 염색체 X 상의 부위 ID 313(서열번호: 44)을 가진 유전자로 이루어진 군으로부터 선택된다.
본 발명의 방법의 또 다른 실시양태에서, 상기 줄기 세포는 만능 줄기 세포, 유도 만능 줄기 세포(iPSC), 신경 전구 세포(neural progenitor cell), 조혈 줄기 세포 또는 배아 줄기 세포(ESC)이다.
본 발명의 방법의 추가 실시양태에서, 상기 줄기 세포는 인간 또는 마우스 줄기 세포이다.
본 발명은 또한 본 발명에 따른 방법 중 어느 하나에 의해 수득된 미세아교세포로서, 바람직하게는 ITGAM(CD11B)(서열번호: 45), ITGAX(CD11C)(서열번호: 46), CD14(서열번호: 47), CD16(서열번호: 48), ENTPD1(CD39)(서열번호: 49), PTPRC(CD45)(서열번호: 50), CD68(서열번호: 51), CSF1R(CD115)(서열번호: 52), CD163(서열번호: 53), CX3CR1(서열번호: 54), TREM2(서열번호: 55), P2RY12(서열번호: 56), TMEM119(서열번호: 57), 및 HLA-DR(서열번호: 58)로 이루어진 군으로부터 선택된 적어도 하나의 미세아교세포 표면 단백질을 발현하는 미세아교세포에 관한 것이다.
본 발명의 추가 실시양태에서, 미세아교세포는 요법(therapy)에 사용하기 위한 것이다.
추가로, 본 발명은 질환의 시험관내 진단을 위한 본 발명에 따른 이러한 미세아교세포의 용도에 관한 것이다. 바람직하게는, 질환은 중추신경계 질환(disease of the central nervous system), 바람직하게는 신경퇴행성 질환(neurodegenerative disease); 보다 바람직하게는 알츠하이머병(Alzheimer's disease), 파킨슨병(Parkinson's disease), 전두측두엽 치매(frontotemporal dementia) 또는 근위축성 측삭 경화증(Amyotrophic Lateral Sclerosis); 신경염증성 또는 자가면역 질환(neuroinflammatory or autoimmune disease), 바람직하게는 다발성 경화증(Multiple Sclerosis), 자가-항체-매개 뇌염(auto-antibody-mediated encephalitis) 또는 감염성 질환(infectious disease), 신경혈관 질환(neurovascular disease); 바람직하게는 뇌졸중(stroke), 혈관염(vasculitis); 외상성 뇌 손상(traumatic brain injury), 및 암(cancer)의 질환으로 이루어진 군으로부터 선택된다.
추가로, 본 발명은 뇌 오가노이드(brain organoid)를 사용한 시험관내 배양을 위한 본 발명에 따른 미세아교세포의 용도에 관한 것이다.
도 1은 4개의 정의된 전사 인자 Klf4, Oct4, c-Myc 및 Sox2를 사용하여 체세포(섬유모세포)를 유도 만능 줄기 세포(iPSC)로 리프로그래밍, 정의된 전사 인자를 사용하여 체세포의 원하는 표적 세포 유형으로의 직접 전환으로서의 직접 리프로그래밍, 만능 줄기 세포로부터 원하는 표적 세포로의 단계적 전환을 나타내는 통상적인 분화 접근법, 및 hPSC의 표적 세포 유형으로의 직접 전환으로서 정방향 프로그래밍인, 세포 제조를 위한 주요 경로의 도식을 나타낸다.(약어: TF = 전사 인자, ESC = 배아 줄기 세포, iPSC = 유도 만능 줄기 세포(ESC 및 iPSC는 만능 줄기 세포(PSC)로 총칭된다))
도 2는 본 발명에서 사용되는 표적화 전략을 나타낸다. dox 유도성 Tet-ON 시스템은 hPSC의 인간 ROSA26 유전자좌(CAG-rtTA) 및 AAVS1 부위(TRE-EGFP)로 표적화되었다.(약어: HAR = 상동성 아암, Neo = 네오마이신-내성 유전자, CAG = 구성적 CAG 프로모터, rtTA = 역 테트라시클린-제어 전사활성인자, Puro = 퓨로마이신-내성 유전자, TRE = 유도성 Tet-반응성 요소, EGFP = 강화된 녹색 형광 단백질, SA = 스플라이스 수용체, T2A = T2A 절단 부위, pA = 폴리-아데닐화 부위)
도 3은 후보 리프로그래밍 인자로서 선택된 미세아교세포 계통의 주요 전사 인자, 이의 코딩 서열의 길이 및 이의 공급원의 표를 나타낸다.
도 4는 분자 클로닝에 의해 생성되고 ROSA26 GSH 또는 AAVS1 GSH의 유전적 변형에 사용된 공여자 플라스미드를 나타낸다.(약어: HAR = 상동성 암, Neo = 네오마이신-내성 유전자, CAG = 구성적 CAG 프로모터, rtTA = 역 테트라시클린-제어 전사활성인자, Puro = 퓨로마이신-내성 유전자, TRE = 유도성 Tet-반응성 요소, EGFP = 강화된 녹색 형광 단백질, SA = 스플라이스 수용체, T2A = T2A 절단 부위, pA = 폴리-아데닐화 부위)
도 5는 미세아교세포 정방향 프로그래밍 프로토콜의 도식을 나타낸다(도 5A 참조). 원시 대식세포 및 미세아교세포에서 발현된 세포 표면 마커의 시간-경과는 유세포 분석법에 의해 평가되었다(n = 2 생물학적 복제)(도 5B 및 도 5C 참조). 20일차 미세아교세포 단독배양(monoculture): 전용 표지된 유동 항체가 이용가능하지 않은 미세아교세포-시그니처 막관통 단백질 TMEM119에 대한 미세아교세포-유사 세포 및 ICC의 위상 대조(phase contrast) 라이브 이미지(도 5D 참조). 20일차 미세아교세포/ 뉴런 공동배양: 세포내 칼슘-결합 단백질 IBA1(AIF1이라고도 공지됨) 및 뉴런 마커 βIII-튜불린(TUBB3)에 대한 ICC(도 5E 참조). 단독배양(20일차)에서 hiPSC 및 미세아교세포의 QPCR(SYBR 그린). 모든 값은 하우스키핑 유전자 GAPDH에 상대적이며 hiPSC에 대해 정규화된다. SPI1 및 CEBPB의 전사물의 경우 두 개의 상이한 프라이머 쌍(서열번호: 80-87; 서열번호: 80: SPI1 전체 정방향 프라이머; 서열번호: 81: SPI1 전체 역 프라이머; 서열번호: 82: SPI1 엔도 정방향 프라이머; 서열번호: 83: SPI1 엔도 역 프라이머; 서열번호: 84: CEBPB 전체 정방향 프라이머; 서열번호: 85: CEBPB 전체 역 프라이머; 서열번호: 86: CEBPB 엔도 정방향 프라이머, 서열번호: NO: 87: CEBPB 엔도 역 프라이머를 참조)를 사용하여, 모든 전사물(전체), 또는 각각의 내인성 유전자좌로부터의 전사물만을 검출하지만 AAVS1-표적화된 이식유전자(엔도)는 검출하지 않았다. 예상된 바와 같이, 이식유전자 발현이 꺼졌기 때문에(프로토콜 10일차에 dox를 철회함으로써), 상대적 발현 수준에서 차이가 검출되지 않았고, 따라서 이는 세포 표현형(F)의 이식유전자-독립성을 확인해 주었다
도 6은 24시간 동안 독시시클린으로 유도된 이중 표적화된 iPS 세포주의 면역세포화학을 나타낸다. 세포는 PU.1 및 CEBPB에 대해 양성이었지만 OCT4에 대해서는 음성이었다.
도 7은 전사 인자 PU.1 및 CEBPB의 코딩 서열을 함유하는 AAVS1 유전자좌의 유전적 변형을 위한, 공여자 플라스미드 pUC_AAVS1_p-Resp-(PU.1-CEBPB)(서열번호: 61)의 지도를 나타낸다.
도 8은 전사 인자 PU.1 및 IRF8의 코딩 서열을 함유하는 AAVS1 유전자좌의 유전적 변형을 위한, 공여자 플라스미드 pUC_AAVS1_p-Resp-(PU.1-IRF8)(서열 번호 62)의 지도를 나타낸다.
도 9는 전사 인자 PU.1 및 RUNX1의 코딩 서열을 함유하는 AAVS1 유전자좌의 유전적 변형을 위한, 공여자 플라스미드 pUC_AAVS1_p-Resp-(PU.1-RUNX1)(서열번호: 63)의 지도를 나타낸다.
도 10은 전사 인자 PU.1의 코딩 서열을 함유하는 AAVS1 유전자좌의 유전적 변형을 위한, 공여자 플라스미드 pUC_AAVS1_p-Resp-(PU.1)(서열번호: 64)의 지도를 나타낸다.
도 11은 전사 인자 PU.1 및 SALL1의 코딩 서열을 함유하는 AAVS1 유전자좌의 유전적 변형을 위한, 공여자 플라스미드 pUC_AAVS1_p-Resp-(PU.1-SALL1)(서열번호: 65)의 지도를 나타낸다.
도 12는 Cas 효소 및 가이드 RNA A의 코딩 서열을 함유하는 플라스미드 ROSA-guideA_Cas9n(서열번호: 66)의 지도를 나타낸다.
도 13은 Cas 효소 및 가이드 RNA B의 코딩 서열을 함유하는 플라스미드 ROSA-guideB_Cas9n(서열번호: 67)의 지도를 나타낸다.
도 14는 구성적 CAG 프로모터 및 rtTA를 함유하는 공여자 플라스미드 pUC_ROSA_n_CAG-rtTA(서열번호: 72)의 지도를 나타낸다.
도 15는 플라스미드 pZFN-AAVS1-L_ELD(서열번호: 68)의 지도를 나타낸다.
도 16은 플라스미드 pZFN-AAVS1-R_KKR(서열번호: 69)의 지도를 나타낸다.
하기 약어가 사용된다: T2A: T2A 펩티드(리보솜 스키핑 신호), puroR: 퓨로마이신 내성 유전자, pA: 폴리아데닐화 신호, CAG: 구성적 CAG 프로모터, TRE3GV: Tet-반응성 요소, HA-R, HA-L: 상동성 아암(우측, 좌측), AmpR: 암피실린 내성 유전자, ori: 복제 기점, NeoR: 네오마이신 내성 유전자, KanR: 카나마이신 내성 유전자.
본 발명은 줄기 세포로부터 미세아교세포를 생산하는 방법으로서, a) 전사 조절인자 단백질을 코딩하는 뉴클레오티드 서열의 제1 게놈성 안전한 하버 부위로의 표적화된 삽입 단계; 및 b) 전사 인자 PU.1의 코딩 서열(서열번호: 1)의 제2 게놈성 안전한 하버 부위로의 표적화된 삽입 단계로서, 여기서 유전자는 전사 조절인자 단백질에 의해 조절되는, 유도성 프로모터에 작동가능하게 연결되는 단계; PU.1(서열번호: 2)의 발현 단계; 및 c) 단계 a) 및 b)로부터 받은 줄기 세포를 미세아교세포의 배아 발달 또는 성체 미세아교세포 증식, 분화 또는 분극화 중 적어도 한 단계 동안 신호전달을 재연하는 적어도 하나의 성장 인자 또는 소분자에 노출시키면서 배양하는 단계를 포함하는, 줄기세포로부터 미세아교세포를 생산하는 방법에 관한 것이다.
한 실시양태에서, 본 발명은 줄기세포로부터 미세아교세포를 생산하는 방법으로서, a) 전사 조절인자 단백질을 코딩하는 뉴클레오티드 서열의 제1 게놈성 안전한 하버 부위로의 표적화된 삽입 단계; 및 b) 전사 인자 PU.1의 코딩 서열(서열번호: 1)의 제2 게놈성 안전한 하버 부위로의 표적화된 삽입 단계로서, 여기서 유전자는 전사 조절인자 단백질에 의해 조절되는, 유도성 프로모터에 작동가능하게 연결되는 단계; PU.1(서열번호: 2)의 발현 단계; 및 c) 단계 a) 및 b)로부터 받은 줄기 세포를 미세아교세포의 배아 발달 또는 성체 미세아교세포 증식, 분화 또는 분극화 중 적어도 한 단계 동안 신호전달을 재연하는 적어도 하나의 성장 인자 또는 소분자에 노출시키면서 배양하는 단계를 포함하는, 줄기세포로부터 미세아교세포를 생산하는 방법에 관한 것이다.
한 실시양태에서, 본 발명은 줄기세포로부터 미세아교세포를 생산하는 방법으로서, a) 전사 조절인자 단백질을 코딩하는 뉴클레오티드 서열의 제1 게놈성 안전한 하버 부위로의 표적화된 삽입 단계; 및 b) 전사 인자 PU.1의 코딩 서열(서열번호: 1)의 제2 게놈성 안전한 하버 부위로의 표적화된 삽입 단계로서, 여기서 유전자는 전사 조절인자 단백질에 의해 조절되는, 유도성 프로모터에 작동가능하게 연결되는 단계; PU.1(서열번호: 2)의 발현 단계; 및 c) 단계 a) 및 b)로부터 받은 줄기 세포를 미세아교세포의 배아 발달 중 적어도 한 단계 동안 신호전달을 재연하는 적어도 하나의 성장 인자 또는 소분자에 노출시키면서 배양하는 단계를 포함하는, 줄기세포로부터 미세아교세포를 생산하는 방법에 관한 것이다.
한 실시양태에서, 본 발명은 줄기 세포로부터 미세아교세포를 생산하는 방법으로서, a) 전사 조절인자 단백질을 코딩하는 뉴클레오티드 서열의 제1 게놈성 안전한 하버 부위로의 표적화된 삽입 단계; 및 b) 전사 인자 PU.1의 코딩 서열(서열번호: 1)의 제2 게놈성 안전한 하버 부위로의 표적화된 삽입 단계로서, 여기서 유전자는 전사 조절인자 단백질에 의해 조절되는, 유도성 프로모터에 작동가능하게 연결되는 단계; PU.1(서열번호: 2)의 발현 단계; 및 c) 단계 a) 및 b)로부터 받은 줄기 세포를 미세아교세포의 배아 발달 중 적어도 한 단계 동안 신호전달을 재연하는 적어도 하나의 성장 인자 또는 소분자에 노출시키면서 배양하는 단계를 포함하는, 줄기 세포로부터 미세아교세포를 생산하는 방법에 관한 것이다.
한 실시양태에서, 본 발명은 또한 줄기 세포로부터 미세아교세포를 생산하는 방법으로서, a) 전사 조절인자 단백질을 코딩하는 뉴클레오티드 서열의 제1 게놈성 안전한 하버 부위로의 표적화된 삽입 단계; 및 b) 전사 인자 PU.1의 코딩 서열(서열번호: 1)의 제2 게놈성 안전한 하버 부위로의 표적화된 삽입 단계로서, 여기서 유전자는 전사 조절인자 단백질에 의해 조절되는, 유도성 프로모터에 작동가능하게 연결되는 단계; PU.1(서열번호: 2)의 발현 단계; 및 c) 단계 a) 및 b)로부터 받은 줄기 세포를 성체 미세아교세포 분화의 적어도 한 단계 동안 신호전달을 재연하는 적어도 하나의 성장 인자 또는 소분자에 노출시키면서 배양하는 단계를 포함하는, 줄기 세포로부터 미세아교세포를 생산하는 방법에 관한 것이다.
한 추가 실시양태에서, 본 발명은 줄기 세포로부터 미세아교세포를 생산하는 방법으로서, a) 전사 조절인자 단백질을 코딩하는 뉴클레오티드 서열의 제1 게놈성 안전한 하버 부위로의 표적화된 삽입 단계; 및 b) 전사 인자 PU.1의 코딩 서열(서열번호: 1)의 제2 게놈성 안전한 하버 부위로의 표적화된 삽입 단계로서, 여기서 유전자는 전사 조절인자 단백질에 의해 조절되는, 유도성 프로모터에 작동가능하게 연결되는 단계; PU.1(서열번호: 2)의 발현 단계; 및 c) 단계 a) 및 b)로부터 받은 줄기 세포를 성체 미세아교세포 분극화의 적어도 한 단계 동안 신호전달을 재연하는 적어도 하나의 성장 인자 또는 소분자에 노출시키면서 배양하는 단계를 포함하는, 줄기 세포로부터 미세아교세포를 생산하는 방법에 관한 것이다.
또 다른 실시양태에서, 본 발명은 줄기 세포로부터 미세아교세포를 생산하는 방법으로서, a) 전사 조절인자 단백질을 코딩하는 뉴클레오티드 서열의 제1 게놈성 안전한 하버 부위로의 표적화된 삽입 단계; 및 b) 전사 인자 PU.1의 코딩 서열(서열번호: 1)의 제2 게놈성 안전한 하버 부위로의 표적화된 삽입 단계로서, 여기서 유전자는 전사 조절인자 단백질에 의해 조절되는, 유도성 프로모터에 작동가능하게 연결되는 단계; PU.1(서열번호: 2)의 발현 단계; 및 c) 단계 a) 및 b)로부터 받은 줄기 세포를 미세아교세포의 배아 발달을 재연하는 적어도 하나의 성장 인자 또는 소분자에 노출시키면서 배양하는 단계를 포함하는, 줄기 세포로부터 미세아교세포를 생산하는 방법에 관한 것이다.
하나의 추가 실시양태에서, 본 발명은 줄기 세포로부터 미세아교세포를 생산하는 방법으로서, a) 전사 조절인자 단백질을 코딩하는 뉴클레오티드 서열의 제1 게놈성 안전한 하버 부위로의 표적화된 삽입 단계; 및 b) 전사 인자 PU.1의 코딩 서열(서열번호: 1)의 제2 게놈성 안전한 하버 부위로의 표적화된 삽입 단계로서, 여기서 유전자는 전사 조절인자 단백질에 의해 조절되는, 유도성 프로모터에 작동가능하게 연결되는 단계; PU.1(서열번호: 2)의 발현 단계; 및 c) 단계 a) 및 b)로부터 받은 줄기 세포를 미세아교세포의 배아 발달 또는 성체 미세아교세포 증식, 분화 또는 분극화 중 적어도 한 단계 동안 신호전달을 모방하는 적어도 하나의 성장 인자 또는 소분자에 노출시키면서 배양하는 단계를 포함하는, 줄기 세포로부터 미세아교세포를 생산하는 방법에 관한 것이다.
하나의 추가 실시양태에서, 본 발명은 줄기 세포로부터 미세아교세포를 생산하는 방법으로서, a) 전사 조절인자 단백질을 코딩하는 뉴클레오티드 서열의 제1 게놈성 안전한 하버 부위로의 표적화된 삽입 단계; 및 b) 전사 인자 PU.1의 코딩 서열(서열번호: 1)의 제2 게놈성 안전한 하버 부위로의 표적화된 삽입 단계로서, 여기서 유전자는 전사 조절인자 단백질에 의해 조절되는, 유도성 프로모터에 작동가능하게 연결되는 단계; PU.1(서열번호: 2)의 발현 단계; 및 c) 단계 a) 및 b)로부터 받은 줄기 세포를 미세아교세포의 배아 발달 중 적어도 한 단계 동안 신호전달을 모방하는 적어도 하나의 성장 인자 또는 소분자에 노출시키면서 배양하는 단계를 포함하는, 줄기 세포로부터 미세아교세포를 생산하는 방법에 관한 것이다.
한 실시양태에서, 본 발명은 또한 줄기 세포로부터 미세아교세포를 생산하는 방법으로서, a) 전사 조절인자 단백질을 코딩하는 뉴클레오티드 서열의 제1 게놈성 안전한 하버 부위로의 표적화된 삽입 단계; 및 b) 전사 인자 PU.1의 코딩 서열(서열번호: 1)의 제2 게놈성 안전한 하버 부위로의 표적화된 삽입 단계로서, 여기서 유전자는 전사 조절인자 단백질에 의해 조절되는, 유도성 프로모터에 작동가능하게 연결되는 단계; PU.1(서열번호: 2)의 발현 단계; 및 c) 단계 a) 및 b)로부터 받은 줄기 세포를 시험관내에서 미세아교세포의 배아 발달을 재연하는 적어도 하나의 성장 인자 또는 소분자에 노출시키면서 배양하는 단계를 포함하는, 줄기 세포로부터 미세아교세포를 생산하는 방법에 관한 것이다.
본 발명내에서 사용된 바와 같이, 용어 "미세아교세포"는 중추신경계의 별개의 세포 집단인 성숙한 세포 유형을 의미한다. 비교 해부학 및 조직학에 정의된 바와 같이, "미세아교세포는 상주하는 조직구-유형 세포이며 CNS의 핵심 선천 면역 이펙터이다. 그들은 종종 휴면하고 있는(즉, 분기됨) 또는 활성화된 것으로 기재되나, 이들 용어는 이의 미세 과정 및 구성적 면역감시 활동의 동적 리모델링을 전달하지 못한다.(…) 증거는 초기 미세아교세포는 난황낭 전구체에서 파생된다는 것을 시사한다 "(Hagan et al., 2012). 미세아교세포가 초기 배아 단계에서 생성되어 성인이 살아가는 동안 내내 뇌에 상주한다는 의미이다.
본 발명에 사용된 바와 같이, 용어 "미세아교세포의 생산"은 줄기 세포로부터 성숙한 세포(미세아교세포)의 생성을 의미하며, 이는 본원에 기재된 바와 같은 본 발명의 방법 중 어느 하나에 의해 수득된다.
본 발명 내에 사용된 바와 같이, 용어 "줄기 세포"는 더 많은 세포를 생산하기 위해 또는 특정한 목적을 갖는 세포로 발달하기 위해 분열할 수 있는 세포의 유형을 의미한다. 본 발명에서, 사용되는 줄기 세포는 만능 줄기 세포일 수 있다. 만능 줄기 세포는 신체의 거의 임의의 세포로 분화할 수 있는 잠재력을 갖는다. 만능 줄기 세포에는 몇몇 공급원이 있다. 배아 줄기 세포(ES 세포)는 초기 착상전 배아인 배반포의 내부 세포 덩어리로부터 유래한 만능 줄기 세포이다. 유도 만능 줄기 세포(iPSC)는 배아줄기 세포의 정의적 특성을 유지하는데 중요한 유전자와 인자를 발현하도록 강요됨으로써 배아 줄기 세포-유사 상태로 유전적으로 리프로그래밍된 성체 세포이다. 2006년에 전사 인자를 코딩하는 4가지 특이적 유전자의 도입이 성체 세포를 만능 줄기 세포로 전환시킬 수 있다는 것이 밝혀졌으나(Takahashi et al., 2006), 후속 작업은 필요한 유전자의 수를 감소시키거나 변경하였다. Oct-3/4 및 특정 구성원의 Sox 유전자 패밀리는 유도 과정에 관여하는 잠재적으로 중대한 전사 조절인자로 확인되었다. Klf 패밀리, Myc 패밀리, Nanog, 및 LIN28의 특정 구성원을 포함한 추가 유전자는 유도 효율을 증가시킬 수 있다. 리프로그래밍 인자에 함유될 수 있는 유전자의 예는 Oct3/4, Sox2, Soxl, Sox3, Soxl5, Soxl7, Klf4, Klf2, c-Myc, N-Myc, L-Myc, Nanog, Lin28, Fbxl5, ERas, ECAT15-2, Tell, 베타-카테닌, Lin28b, Sall1, Sall4, Esrrb, Nr5a2, Tbx3 및 Glisl를 포함하며, 이들 리프로그래밍 인자는 단독으로, 또는 이의 둘 이상의 종류를 조합하여 사용할 수 있다.
유도성 카세트의 삽입에 의해 변형된 세포가 인간 환자에서 사용되는 경우, 세포가 그 개체로부터 유래된 iPSC인 것이 바람직할 수 있다. 자가 세포의 이러한 사용은 세포를 수령자와 매칭시킬 필요를 제거할 것이다. 대안적으로, 관련 기술분야의 통상의 기술자에게 공지된 상업적으로 이용가능한 iPSC가 사용될 수 있다. 대안적으로, 세포는 자가이거나 공여될 수도 있는, 조직-특이적 줄기 세포일 수 있다. 적합한 세포는 외배반(epiblast) 줄기 세포, 유도 신경 줄기 세포 및 기타 조직-특이적 줄기 세포를 포함한다.
본 발명의 방법의 일부 실시양태에서, 사용된 줄기 세포는 배아 줄기 세포 또는 줄기 세포주인 것이 바람직할 수 있다. 수많은 배아 줄기 세포주, 예를 들어, WA01(HI), WA09(H9), KhES-1, KhES-2 및 KhES-3이 현재 이용 가능하다. 배아를 파괴하지 않고 유래된 줄기 세포주가 이용가능하다. 본 발명은 인간 배아의 파괴를 포함하는 임의의 방법까지 미치지 않는다.
본 발명 내에 사용된 바와 같이, 용어 "표적화된 삽입"은 게놈성 안전한 하버(GSH) 부위로의 삽입을 의미하며, 이는 바람직하게는 구체적으로 다른 곳에 기재된 바와 같은 GSH의 서열 내에 있다. 폴리뉴클레오티드를 특이적 서열에 삽입하기 위한 임의의 적합한 기술이 사용될 수 있으며, 몇 가지가 관련 기술분야에 기재되어 있다. 적합한 기술은 원하는 위치에 파단(break)을 도입하고 갭(gap)으로 벡터의 재조합을 허용하는 관련 기술분야의 통상의 기술자에게 공지된 임의의 방법을 포함한다. 따라서, 표적 부위-특이적 게놈 변형을 위한 중대한 단계는 변형될 게놈 유전자좌에서 이중 가닥 DNA 파단(DSB)을 생성하는 것이다. DSB를 복구하고 원하는 시퀀스를 도입하기 위해 구별되는 세포 복구 메커니즘을 이용할 수 있으며, 이들은 오류가 발생하기 쉬운 비-상동 말단 연결 복구(non-homologous end joining repair)(NHEJ); 및 유도성 카세트를 삽입하는데 사용할 수 있는 공여자 DNA 주형에 의해 매개되는 상동 재조합 복구(homologous recombination repair)(HR)이다.
게놈에서 DSB의 맞춤형 부위-특이적 생성을 가능하게 하는 몇몇 기술이 존재한다. 이들 중 다수는 아연 핑거 뉴클레아제(ZFN), 전사 활성인자-유사 이펙터 뉴클레아제(TALEN) 또는 클러스터화된 규칙적으로 간격을 둔 짧은 회문 반복부/ RISPR 연관 단백질(CRISPR/Cas9) 시스템과 같은 맞춤형 엔도뉴클레아제의 사용을 포함한다(Gaj et al., 2013). 아연 핑거 뉴클레아제는 제한 효소 Fokl의 뉴클레아제 도메인에 징크-핑거 DNA-결합 도메인의 융합에 의해 생성되는 인공 효소이다. 후자는 DNA를 절단하기 위해 이량체화되어야 하는 비특이적 절단 도메인을 갖는다. 이는 Fokl 도메인의 이량체화를 허용하고 DNA를 절단하기 위해 2개의 ZFN 단량체가 필요함을 의미한다. DNA 결합 도메인은 관심 임의의 게놈 서열을 표적으로 하도록 설계될 수 있으며, Cys2His2 아연 핑거의 탠덤 어레이일 수 있으며, 이들 각각은 표적 서열에서 3개의 연속 뉴클레오티드를 인식한다. 2개의 결합 부위는 Fokl 도메인의 최적 이량체화를 허용하기 위해 5-7 bp에 의해 분리된다. 따라서 효소는 특정 부위에서 DNA를 절단할 수 있으며, 이중 가닥 파단을 달성하기 위해 두 개의 근위 DNA-결합 사건이 발생하여야 함을 보장함으로써 표적 특이성이 증가된다. 전사 활성인자-유사 이펙터 뉴클레아제, 또는 TALEN는, 이량체 전사 인자 /뉴클레아제이다. 이들은 TAL 이펙터 DNA-결합 도메인을 DNA 절단 도메인(뉴클레아제)에 융합함으로써 만들어진다. 이들은 임의의 원하는 DNA 서열에 실제로 결합하도록 조작될 수 있으므로, 뉴클레아제와 조합시, DNA가 특정 위치에서 절단될 수 있다. TAL 이펙터는 크산토모나스(Xanthomonas) 박테리아에 의해 분비되는 단백질이며, 이의 DNA 결합 도메인은 분기하는 12번째 및 13번째 아미노산과 함께 고도로 보존된 33-34개 아미노산 서열을 함유한다. 이들 두 위치는 매우 가변적이며 특이적 뉴클레오티드 인식과 강한 상관관계를 나타낸다. 아미노산 서열과 DNA 인식 사이의 이러한 직접적인 관계는 두 개의 가변 위치에 적절한 잔기를 함유하는 반복 세그먼트의 조합을 선택함으로써 특정 DNA-결합 도메인의 조작을 가능하게 하였다. 따라서 TALEN은 각각 단일 뉴클레오티드를 표적으로 하는, 33 내지 35개의 아미노산 모듈의 어레이로부터 구축된다. 모듈의 어레이를 선택함으로써, 거의 임의의 서열이 표적화될 수 있다. 사용된 뉴클레아제는 Fokl 또는 이의 유도체일 수 있다.
세 가지 유형의 CRISPR 메커니즘이 확인되었으며, 그 중 유형 II가 가장 잘 연구되었다. CRISPR/Cas9 시스템(유형 II 시스템)은 Cas9 뉴클레아제를 이용하여 짧은 가이드 RNA에 의해 결정된 부위에서 DNA의 이중 가닥 파단을 만든다. 각각의 반복부에 뒤이어 이전에 외래 유전적 요소에 노출된 "프로토스페이서 DNA"의 짧은 세그먼트가 뒤따른다. CRISPR 스페이서는 RNA 간섭을 사용하여 외인성 유전적 요소를 인식하고 커트한다. CRISPR/Cas 시스템은 외부 유전적 요소에 대한 내성을 부여하는 원핵생물 면역 시스템이다. CRISPR은 염기 서열의 짧은 반복부를 함유하는 원핵생물 DNA의 세그먼트이다. CRISPR 면역 반응은 CRISPR-RNA(crRNA) 생합성 및 crRNA-가이드 간섭의 두 단계를 통해 발생한다. CrRNA 분자는 프로토스페이서 DNA에서 전사된 가변 서열 및 CRISP 반복부로 구성된다. 이어서 각각의 crRNA 분자는 트랜스-활성화 CRISPR RNA(tracrRNA)로 공지된 두 번째 RNA와 혼성화하고 이들 두 가지가 함께 결국 뉴클레아제 Cas9와 복합체를 형성한다. crRNA의 프로토스페이서 DNA 코딩 섹션은 Cas9가 프로토스페이서 인접 모티프(PAM)로서 공지된 짧은 서열에 인접한 경우, 상보적인 표적 DNA 서열을 절단하도록 지시한다. 이 자연 시스템은 다른 많은 적용 중에서, 게놈 DNA의 특정 부위에 DSB 파단을 도입하도록 조작 및 활용되었다. 특히, 스트렙토코커스 피오게네스(Streptococcus pyogenes)로부터의 CRISPR 유형 II 시스템이 사용될 수 있다. 가장 간단하게, CRISPR/Cas9 시스템은 게놈 편집을 제공하기 위해 세포에 전달되는 두 가지 구성요소, 즉 Cas9 뉴클레아제 자체 및 작은 가이드 RNA(gRNA)로 구성된다. gRNA는 맞춤형, 부위-특이적 crRNA(표적 서열을 지향함) 및 표준화된 tracrRNA의 융합이다.
일단 DSB가 만들어지면, 표적화 유전자좌에 상동성을 가진 공여자 주형이 제공된다. DSB는 정밀한 삽입이 이루어질 수 있도록 하는 상동성-지향 복구(HDR) 경로에 의해 복구될 수 있다. 이 시스템의 파생물이 또한 가능하다. 단지 닉카제 활성만을 가진 Cas9D10A와 같은 Cas9의 돌연변이체 형태가 이용가능하다. 이는, 즉 하나의 DNA 가닥을 절단하고 NHEJ를 활성화하지 않는다. 대신에, 상동 수리 주형이 제공되는 경우, DNA 복구는 높은-충실도의 HDR 경로를 통해서만 수행된다. Cas9D10A는 표적 부위의 반대 가닥 상의 인접 영역에 상보적인, 2개의 sgRNA와 함께 인접 DNA 닉을 생성하도록 설계된 쌍형성한 Cas9 복합체에서 사용될 수 있으며, 이는 특히 유리할 수 있다. 이중-가닥 DNA 절단을 만들기 위한 요소는 세포에서 발현하기 위한 플라스미드와 같은 하나 이상의 벡터에 도입될 수 있다. 따라서, 뉴클레오티드 서열/ 유전자/ 유도성 카세트의 삽입을 허용하기 위해 게놈에서 특이적이고 표적화된 이중 가닥 파단을 만드는 임의의 방법이 본 발명의 방법에서 사용될 수 있다. 본 발명의 방법은 ZFN, TALEN 및/또는 CRISPR/Cas9 시스템 또는 이의 임의의 유도체 중 임의의 하나 이상을 유전자/ 유도성 카세트를 삽입하기 위해 이용하는 것이 바람직할 수 있다.
일단 DSB가 임의의 적절한 수단에 의해 만들어지면, 삽입을 위한 유전자/ 유도성 카세트는 하기에 기재된 바와 같은 임의의 적합한 방식으로 공급될 수 있다. 유전자/ 유도성 카세트 및 연관 유전적 물질은 DSB에서 DNA의 복구를 위한 공여자 DNA를 형성하고 표준 세포 복구 기계/ 경로를 사용하여 삽입된다. 파단이 시작되는 방법은 상기에 언급한 바와 같이, 손상을 복구하는데 사용되는 경로를 변경한다. 그러나 이것은 또한 관련 기술분야의 통상의 기술자의 지식 범위 내에 있다.
본 발명 내에서 사용된 바와 같이, 용어 "유전자"는 기본 물리적 단위 유전, 단백질로 번역될 때 유전적 특질을 야기하는, RNA의 합성을 위한 코딩된 지침을 제공하는 DNA 세그먼트를 따른 뉴클레오티드의 선형 서열을 의미한다.
본 발명 내에서 사용된 바와 같이, 용어 "뉴클레오티드 서열"은 상기에 정의된 바와 같은 유전자를 형성하는 DNA 세그먼트 내의 염기의 연속을 지칭한다.
본 발명 내에서 사용된 바와 같이, 용어 "전사 조절인자 단백질"은 DNA, 바람직하게는 프로모터 내부 또는 근처에 위치한 DNA 부위에 서열-특이적으로 결합하고, 프로모터에 전사 기구의 결합, 그리고 따라서 DNA 서열의 전사(전사 활성인자)를 촉진하거나 이 과정을 차단하는(전사 억제인자) 단백질을 의미한다. 전사 조절인자 단백질이 결합하는 DNA 서열은 전사 인자-결합 부위 또는 반응 요소라고 칭하며, 이들은 조절된 DNA 서열의 프로모터 내에 또는 근처에서 발견된다. 반응성 요소는 본 발명의 일부이다. 전사 활성인자 단백질은 반응 요소에 결합하여 유전자 발현을 촉진한다. 이러한 단백질은 유도성 카세트 발현을 제어하기 위한 본 발명의 방법에서 바람직하다. 이러한 독립체는 또한 전사 인자라고도 공지되어 있다. 전사 억제인자 단백질은 반응 요소에 결합하여 유전자 발현을 방지한다. 전사 조절인자 단백질은 물질의 결합, 다른 전사 인자와의 상호작용(예를 들어, 동종- 또는 이종-이량체화) 또는 공조절 단백질, 인산화, 및/또는 메틸화를 포함한 다수의 메커니즘에 의해 활성화 또는 탈활성화될 수 있다. 전사 조절인자는 활성화 또는 비활성화에 의해 제어될 수 있다. 전사 조절인자 단백질이 전사 활성인자 단백질인 경우, 전사 활성인자 단백질이 활성화를 필요로 하는 것이 바람직하다. 이러한 활성화는 임의의 적절한 수단을 통해 이루어질 수 있으나, 전사 조절인자 단백질은 줄기 세포에 외인성 물질의 첨가를 통해 활성화되는 것이 바람직하다. 줄기 세포에 대한 외인성 물질의 공급을 제어할 수 있으며, 따라서 전사 조절인자 단백질의 활성화를 제어할 수 있다. 이러한 전사 조절인자 단백질은 또한 유도성 전사 조절인자 단백질이라 칭해진다.
본 발명 내에서 사용된 바와 같이, 용어 "전사 인자"는 DNA, 바람직하게는 프로모터 내부 또는 근처에 위치한 DNA 부위에 서열-특이적으로 결합하고, 프로모터에 전사 기구의 결합, 그리고 따라서 DNA 서열의 전사(전사 활성인자)를 촉진하거나 이 과정을 차단하는(전사 억제인자) 단백질을 의미한다. 본 발명의 맥락에서, 전사 인자는 원하는 유전자 서열, 바람직하게는 유도성 카세트와 함께 세포 내로 전달되는 DNA 서열이다. 유도성 카세트를 게놈에 도입은 유전자 발현을 허용하는 유전자 서열을 추가하여 해당 세포의 표현형을 변경할 가능성을 갖는다. 본 발명의 방법은 세포에서 유도성 카세트 내에 전사 인자의 세트의 유전자 서열(들)의 제어가능한 전사를 제공한다.
마스터 조절인자는 전사 인자, 전사 조절인자, 시토카인 수용체 또는 신호전달 분자 등 중 하나 이상일 수 있다. 마스터 조절인자는 그것을 발현하는 세포의 계통에 영향을 미치는 발현된 유전자이다. 세포의 계통을 결정하기 위해서마스터 조절인자의 네트워크가 필요할 수 있다. 본원에 사용된 바와 같이, 발달 계통 또는 세포 유형의 시작 시에 발현되는 마스터 조절인자 유전자는 다수의 하류 유전자를 직접적으로 또는 유전자 발현 변화의 캐스케이드를 통해 조절함으로써 해당 계통의 사양에 참여한다. 마스터 조절인자가 발현되는 경우 다른 계통을 형성할 예정인 세포의 운명을 재-특정하는 능력을 갖는다. 본 발명의 방법에서 사용될 수 있는 전사 인자는 PU.1(서열번호: 2)(유전자 SPI1, 서열번호: 1) , CEBPB(서열번호: 3), RUNX1(서열번호: 4), IRF8(서열번호: 5), 및 SALL1(서열번호: 6)을 포함한다.
본 발명 내에서 사용된 바와 같이, 용어 "PU.1"(서열번호: 2)은 조혈 전사 인자 PU.1로도 공지된 전사 인자, Spi-1 원-종양유전자(proto-oncogene), 31 kDa 형질전환 단백질, 전사 인자 PU.1, 비장 집중 형성 바이러스(SFFV) 프로바이러스 통합 종양유전자 Spi1, 비장 집중 형성 바이러스(SFFV) 프로바이러스 통합 종양유전자, 또는 31 kDa-형질전환 단백질, SFPI1, SPI-1, SPI-A, PU.1 또는 OF를 의미하며, 여기서 "SPI1"은 골수성 및 B-림프구성 세포 발달 동안 유전자 발현을 활성화하는 ETS-도메인 전사 인자를 코딩하는 유전자(서열번호: 1)(Spi-1 원-종양유전자)를 의미한다.
본 발명 내에서 사용된 바와 같이, 용어 "게놈성 안전한 하버 부위"는 세포에 유해한 영향 없이 유전적 물질의 삽입을 허용하고 삽입된 유전적 물질의 전사를 허용하는 유전적 부위를 의미한다. 관련 기술분야의 통상의 기술자는 이들 단순화된 기준을 사용하여 적합한 GSH, 및/또는 보다 공식적인 기준을 확인할 수 있다. 게놈성 안전한 하버 부위(GSH) 내 삽입은 무작위 게놈 통합보다 선호되는데, 그 이유는 이것이 게놈의 더 안전한 변형으로 예상되고, 암성 세포 유형을 야기하는 돌연변이를 유발하거나 자연 유전자 발현을 침묵하는 것과 같은 원치 않는 부작용을 야기할 가능성이 더 적기 때문이다. 따라서, 게놈성 안전한 하버 부위는 게놈 내의 유전자좌이며, 여기서 유전자 또는 다른 유전적 물질은 세포 또는 삽입된 유전적 물질에 대한 어떤 유해한 영향도 없이 삽입될 수 있다. 가장 유익한 것은 삽입된 유전자 서열의 발현이 인접 유전자로부터의 임의의 리드-쓰루(read-through) 발현 및 유도성 카세트의 발현에 의해 교란되지 않고, 내인성 전사 프로그램에 대한 간섭을 최소화하는 GSH 부위이다. 특정한 유전자좌가 추후 GSH 부위에 있는지 여부를 결정하는데 도움이 되는 더욱 공식적인 기준이 제안되었다(Pellenz et al., 2019). 이러한 기준은(i) 모든 종양유전자 목록의 임의의 암-관련 유전자로부터 > 300 kb,(ii) 임의의 miRNA/ 기타 기능적인 소형 RNA로부터 > 300 kb,(iii) 임의의 5' 유전자로부터 > 50 kb,(iv) 임의의 복제 기점로부터 > 50 kb 떨어져 있음,(v) 임의의 초보존된 요소로부터 > 50 kb 떨어져 있음,(vi) 낮은 전사 활성(mRNA 없음 ± 25　kb),(vii) 카피 수 가변 영역에 없음(viii) 개방 염색질(DHS 신호 ± 1 kb) 및(ix) 고유한(인간 게놈에서 1개 카피)인 부위를 포함한다. 이미 확인된 GSH가 이들 기준 모두를 충족시키지는 않기 때문에, 이들 제안된 기준 모두를 충족시킬 필요는 없을 수 있다. 적합한 GSH는 이들 기준 중 적어도 3, 4, 5, 6, 7 또는 8개, 가장 바람직하게는 9개 모두를 충족시킬 것으로 생각된다.
본 발명의 방법에서, 삽입은 상이한 GSH에서 발생한다. 제1 GSH는 전사 조절인자 단백질의 삽입에 의해 변형된다. 제2 GSH는 유도성 프로모터에 작동가능하게 연결된 코딩 서열을 포함하는 유도성 카세트의 삽입에 의해 변형된다. 다른 유전적 물질 또한 이들 요소 중 하나 또는 둘 다에 의해 삽입될 수 있다. 유도성 카세트 내의 유도성 프로모터에 작동가능하게 연결된 유전자 서열은 바람직하게는 DNA 서열이다. 유도성 카세트의 유전자 서열(들)은 바람직하게는 RNA 분자를 코딩하고, 따라서 전사될 수 있다. 전사는 유도성 프로모터를 사용하여 제어된다. RNA 분자는 임의의 서열일 수 있으나, 바람직하게는 단백질, shRNA 또는 gRNA를 코딩하는 mRNA이다.
제1 GSH는 임의의 적합한 GSH 부위일 수 있다. 임의로, 이는 구성적으로 발현되는 내인성 프로모터를 가진 GSH이며, 이는 구성적으로 발현되는 삽입된 전사 조절인자 단백질을 결과할 것이다. 적합한 GSH는 인간 세포에 대한 hROSA26 부위이다. 본 발명의 추가 실시양태에서, 프로모터에 작동가능하게 연결된 삽입된 전사 조절인자 단백질은 구성적 프로모터이다. 구성적 프로모터는, 예를 들어, hROSA26 부위에서의 삽입물과 함께 사용될 수 있다.
본 발명 내에서 사용된 바와 같이, 용어 "유도성 프로모터"는 폴리뉴클레오티드의 전사를 개시하고 조절하는 뉴클레오티드 서열을 의미한다. "유도성 프로모터"는 프로모터에 작동가능하게 연결된 유전자 서열의 발현이 분석물, 보조-인자, 조절 단백질 등에 의해 제어되는 뉴클레오티드 서열이다. 본 발명의 방법의 한 실시양태에서, 제어는 전사 조절인자 단백질에 의해 영향을 받는다. 용어 "프로모터" 또는 "제어 요소"는 전장 프로모터 영역 및 이들 영역의 기능적(예를 들어, 전사 또는 번역을 제어하는) 세그먼트을 포함하는 것으로 의도된다. 전사 조절인자 단백질을 코딩하는 유전자는 구성적 프로모터에 작동가능하게 연결되어 있는 것이 바람직하다. 대안적으로, 제1 GSH는 전사 조절인자 단백질 유전자 및 임의의 연관 유전적 물질의 발현을 또한 구동할 수 있는 구성적 프로모터를 이미 갖도록 선택될 수 있다. 구성적 프로모터는 지속적이고 높은 수준의 유전자 발현을 보장한다. 통상적으로 사용되는 구성적 프로모터는 인간 β-액틴 프로모터(ACTB), 시토메갈로바이러스(CMV), 신장 인자-la(EFla), 포스포글리세레이트 키나제(PGK) 및 유비퀴틴 C(UbC)를 포함한다. CAG 프로모터는 높은 수준의 유전자 발현을 유도하는데 빈번히 사용되는 강력한 합성 프로모터이다.
본 발명 내에서 사용된 바와 같이, 용어 "배양"은 성장을 보장하는 적합한 조건 하에 박테리아 및 효모와 같은 미생물, 또는 인간, 식물, 또는 동물 세포의 성장을 의미하며, 이는 관련 기술분야의 통상의 기술자의 지식이다.
본 발명 내에서 사용된 바와 같이, 용어 "성장 인자"는 자가분비, 측분비 또는 내분비 방식으로 세포 활성을 제어하는 신호전달 분자를 의미한다. 본원에 사용된 바와 같이, 본 발명의 맥락에서, 용어 "성장 인자"는 "시토카인"과 상호교환적으로 사용될 수 있다. 성장 인자 또는 시토카인은 유기체의 상이한 세포 유형에 의해 생성되고 특정 수용체에 결합하고 연관 하류 신호전달 경로를 활성화하여, 차례로 핵에서 유전자 전사를 조절하고 궁극적으로 조절 세포 과정 예컨대 세포 분열, 세포 생존, 세포 분화, 부착 및 이동을 포함한 생물학적 반응을 자극함으로써 생물학적 기능을 발휘한다.
본 발명 내에서 사용된 바와 같이, 용어 "소분자"는 자연적으로 또는 인공적으로 생성되고 세포막을 통해 확산될 수 있고 신호전달 경로를 조절할 수 있는 생물성 분자를 의미한다. 본 발명 내에서 바람직하게 사용되는 소분자는 LY294002 및 CHIR99021과 같이 각각 포스파티딜이노시톨 3-키나제(PI3K) 및 글리코겐 신타제 키나제 3을 억제할 수 있다.
본 발명 내에서 사용된 바와 같이, 용어 "신호전달을 재연하는"은 성장 인자 및/또는 케모카인과 같은 분비된 분자의 기능을 시뮬레이션, 모방 또는 유사하게 하여 자연 환경에서 세포에 영향을 미치고 그에 의해 이들 작용에 의해 미세아교세포를 생성할 수 있는 것을 의미한다.
본 발명 내에서 사용된 바와 같이, 용어 "신호전달을 모방하는"은 성장 인자 및/또는 케모카인과 같은 분비된 분자의 기능을 시뮬레이션, 모방, 유사하게 하거나 재연하여 자연 환경에서 세포에 영향을 미치고 그에 의해 이들 작용에 의해 미세아교세포를 생성할 수 있는 것을 의미한다.
본 발명 내에서 사용된 바와 같이, 용어 "미세아교세포의 배아 발달"은 인간 배아, 태아 및 출생 후 발달 동안 발달 중인 미세아교세포 분화의 귀착점(sequel)에 따라 만능 줄기 세포가 성숙한 미세아교세포로 단계적으로, 착상 전 배반포-계 배아로부터 완전히-확립되고 자체-지되는 미세아교세포 집단에 이르기까지, 전이하는 것을 의미한다.
본 발명 내에서 사용된 바와 같이, 용어 "성체 미세아교세포 증식"은 성숙한 미세아교세포를 야기하는 임의의 세포 분열 과정을 의미한다.
본 발명 내에서 사용된 바와 같이, 용어 "성체 미세아교세포 분화"는 미세아교세포 전구체 상태에 있는 세포가 항상성/ 휴면 상태에서 미세아교세포의 전형적인 특징을 포함하는, 성체 미세아교세포 유형으로 분화하는 것을 의미한다.
본 발명 내에서 사용된 바와 같이, 용어 "성체 미세아교세포 분극화"는 손상된 뉴런, 아교 세포, 또는혈액 뇌 장벽 기능 장애로 인한 혈장 단백질 노출로부터의 각각 신호인 세포외 환경에 의해 제공되는 세포외 자극에 대한 성숙한 미세아교세포의 반응을 의미한다. 이 미세아교세포 반응은 손상 부위를 향한 미세아교 세포의 이동을 포함하며 신경보호 또는 신경독성 효과를 가질 수 있다.
추가로, 본 발명의 방법의 한 실시양태에서, 적어도 하나의 성장 인자 또는 소분자는 액티빈 A(서열번호: 7), BMP4(서열번호: 8), FGF(서열번호: 9), VEGF-A(서열번호: 10), LY294002, CHIR99021, SCF(서열번호: 11), IL-3(서열번호: 12), IL-6(서열번호: 13), CSF1(서열번호: 14), IL-34(서열번호: 15), CSF2(서열번호: 16), CD200(서열번호: 17), CX3CL1(서열번호: 18), TGFβ1(서열번호: 19), 및 IDE1로 이루어진 군으로부터 선택된다.
본원에서 사용된 바와 같은 액티빈 A(서열번호: 7)는 액티빈 베타-A쇄, EDF, 적혈구계(Erythroid) 분화 단백질, FRP, FSH-방출 단백질, INHBA, 인히빈 베타-A쇄, 인히빈 베타-1을 의미한다. 이 유전자에 의해 코딩되는 단백질은 만능 줄기 세포, 내배엽 및 중배엽에 의해 생성된 단백질의 형질전환 성장 인자 베타(TGF-β) 패밀리의 구성원이다.
본 발명에서 사용된 바와 같은 BMP4(서열번호: 8)는 ZYME, BMP2B 또는 BMP2B1로도 공지된 골 형태발생 단백질(bone morphogenetic protein) 4를 의미한다. 이 유전자에 의해 코딩되는 단백질은 형질전환 성장 인자-베타 슈퍼패밀리의 일부인 골 형태발생 단백질 패밀리의 구성원이다.
본 발명에서 사용된 바와 같은 FGF(서열번호: 9)는 섬유모세포 성장인자를 의미한다. 이 유전자에 의해 코딩되는 단백질은 예를 들어 문헌 [Hui et al., 2018]에 기재된 바와 같은 세포 신호전달 단백질의 구성원이다 Hui et al., 2018.
본 발명에서 사용된 바와 같은 VEGF-A(서열번호: 10)는 VPF, VEGF 또는 MVCD1로도 공지된 혈관 내피 성장 인자 A를 의미한다. 이 유전자에 의해 코딩되는 단백질은 PDGF/VEGF 성장 인자 패밀리의 구성원이며 헤파린-결합 단백질이다. 이 성장 인자는 혈관 내피 세포의 증식 및 이동을 유도하며, 생리학적 및 병리학적 혈관신생 둘 다에 필수적이다.
본 발명에서 사용된 바와 같이, LY294002는 효소의 ATP 결합 부위에 작용하는 포스파티딜이노시톨 3-키나제(PI3K)의 강력한 세포 투과성 억제제를 의미한다(Vlahos et al., 1994). 이의 화학 구조는 하기에 주어져 있다:
Figure pct00002
본 발명에서 사용된 바와 같은 CHIR99021은 GSK3β(ICC50 = 6.7 nM) 및 GSK3α(ICC50 = 10 nM)를 억제하는 글리코겐 신타제 키나제 3의 매우 강력한 억제제이며 WNT 활성인자로서 기능하는 아미노 피리미딘 유도체를 의미한다. 이의 화학 구조는 하기에 주어져 있다:
Figure pct00003
본 발명에서 사용된 바와 같은 SCF(서열번호: 11)는 Kit 리간드, 비만 세포 성장 인자 또는 스틸 인자(Steel factor)로도 공지된 줄기 세포 인자를 의미한다. 이 유전자에 의해 코딩되는 단백질은 배아 및 성체 조혈의 조절에서 중추적인 역할을 하는 초기 작용 시토카인이다.
본 발명에서 사용된 바와 같은 IL-3(서열번호: 12)은 인터루킨-3, MCGF(비만 세포 성장 인자), Multi-CSF, HCGF, P-세포 자극 인자, MGC79398 또는 MGC79399를 의미한다. 이 유전자에 의해 코딩되는 단백질은 성장 촉진 시토카인이다.
본 발명에서 사용된 바와 같은 IL-6(서열번호: 13)은 B-세포 자극 인자 2, CTL 분화 인자, 하이브리도마 성장 인자, 인터페론 베타-2, 인터루킨-6, IFN-베타-2, IFNB2, BSF-2, CDF, 인터페론, 베타 2, B-세포 분화 인자, 인터페론, 베타 2, 인터루킨 BSF-2, BSF2, HGF 또는 HSF로도 공지된 인터루킨 6을 의미한다. 이 유전자에 의해 코딩되는 단백질은 염증 및 B 세포의 성숙에서 기능하는 시토카인이다.
본 발명에서 사용된 바와 같은 CSF1(서열번호: 14)은 콜로니 자극 인자 1(대식세포), 대식세포 콜로니-자극 인자 1, 대식세포 콜로니 자극 인자 1, 라니모스팀(Lanimostim), CSF-1, MCSF, M-CSF로도 공지된 콜로니 자즉 인자 1이며 이 유전자에 의해 코딩되는 단백질은 대식세포의 생산, 분화, 및 기능을 제어하는 시토카인이다.
본 발명에서 사용된 바와 같은 IL-34(서열번호: 15)는 C16 또는 f77로도 공지된 인터루킨 34를 의미한다. 이 유전자에 의해 코딩되는 단백질은 콜로니-자극 인자-1 수용체를 통해 단핵구 및 대식세포의 분화 및 생존력을 촉진하는 시토카인이다.
본 발명에서 사용된 바와 같은 CSF2(서열번호: 16)는 사르그라모스팀(Sargramostim), 콜로니 자극 인자 2(과립구-대식세포), 과립구-대식세포 콜로니-자극 인자, 몰그라모스틴(Molgramostin), 몰그라모스팀(Molgramostim), GMCSF, CSF, 과립구 대식세포-콜로니 자극 인자, 과립구-대식세포 콜로니 자극 인자, 콜로니-자극 인자, GM-CSF로도 공지된 콜로니 자극 인자 2를 의미한다, 이 유전자에 의해 코딩되는 단백질은 과립구와 대식세포의 생산, 분화 및 기능을 제어하는 시토카인이다.
본 발명에서 사용된 바와 같은 CD200(서열번호: 17)은 CD200 분자, CD200 항원, 모노클로날 항체 MRC OX-2에 의해 확인되는 항원, OX-2 막 당단백질, MOX1, MOX2, OX-2 또는 MRC에 의해 확인된 항원으로도 공지된 CD200 유전자를 의미한다. 이 유전자에 의해 코딩되는 단백질은 2개의 세포외 면역글로불린 도메인, 막관통 및 세포질 도메인을 함유하는 유형 I 막 당단백질이다.
본 발명에서 사용된 바와 같은 CX3CL1(서열번호: 18)은 C-X3-C 모티프 케모카인 리간드 1, 소형 유도성 시토카인 서브패밀리 D(Cys-X3-Cys), 구성원 1(프랙탈카인, 뉴로탁틴), 케모카인(C-X3-C 모티프) 리간드 1, CX3C 막-고정된(Membrane-Anchored) 케모카인, 소형-유도성 시토카인 D1, C-X3-C 모티프 케모카인 1, 뉴로탁틴, 프랙탈카인, 또는 SCYD1, NTT, 소형 유도성 시토카인 서브패밀리 D(Cys-X3-Cys), 구성원-1, C3Xkine, ABCD-3, CXC3C, CXC3, NTN 또는 FKN로도 공지된 CX3CL1 유전자를 의미한다. 이 유전자에 의해 코딩되는 단백질은 보존된 시스테인 잔기 사이에 위치한 아미노산의 수를 특징으로 하는, 케모카인의 CX3C 서브그룹에 속한다.
본 발명에서 사용된 바와 같은 TGFβ1(서열번호: 19)은 형질전환 성장 인자 베타-1 전구단백질, 프리프로(Prepro)-형질전환 성장 인자 베타-1, TGFB, 형질전환 성장 인자, 베타 1, 형질전환 성장 인자 베타-1, 잠복기-연관 펩티드, 카무라티-엥겔만병(Camurati-Engelmann Disease), TGF-베타-1, IBDIMDE, TGF베타, DPD1, CED 또는 LAP로도 공지된 형질전환 성장 인자 베타 1을 의미한다. 이 유전자에 의해 코딩되는 단백질은 단백질의 TGF-베타(형질전환 성장 인자-베타) 슈퍼패밀리의 분비된 리간드이다.
본 발명의 방법의 추가 실시양태에서, 적어도 하나의 성장 인자는 CSF1(서열번호: 14) 또는 IL-34(서열번호: 15)이다. 본 발명의 방법의 추가 실시양태에서, 적어도 하나의 성장 인자는 CSF1(서열번호: 14)이다. 본 발명의 방법의 추가 실시양태에서, 적어도 하나의 성장 인자는 IL-34(서열번호: 15)이다.
본 발명의 방법의 추가 실시양태에서, 적어도 하나의 소분자는 CHIR99021, LY294002 또는 IDE1이다.
본 발명에서 사용된 바와 같은 LY294002는 효소의 ATP 결합 부위에 작용하는 포스파티딜이노시톨 3-키나제(PI3K)의 강력한 세포 투과성 억제제를 의미한다(Vlahos et al., 1994). 이의 화학 구조는 하기에 주어진다:
Figure pct00004
본 발명에서 사용된 바와 같은 CHIR99021은 GSK3β(ICC50 = 6.7 nM) 및 GSK3α(ICC50 = 10 nM)를 억제하는 글리코겐 신타제 키나제 3의 강력한 억제제이며 WNT 활성인자로서 기능하는 아미노 피리미딘 유도체를 의미한다. 이의 화학 구조는 하기에 주어져 있다:
Figure pct00005
본 발명에서 사용된 바와 같은 IDE1은 최종적인 내배엽의 유도인자(inducer of definitive endoderm); TGF-베타 경로를 활성화하고 성장 인자 TGF-베타의 대체물로 사용될 수 있는 소분자를 의미한다. 이의 화학 구조는 하기에 주어진다:
Figure pct00006
본 발명의 방법의 또 다른 실시양태에서, 제1 및 제2 게놈성 안전한 하버 부위는 상이하다.
본 발명의 방법의 추가 실시양태에서, 방법은 전사 인자 CEBPB의 유전자의 코딩 서열(서열번호: 3)의 삽입 및 이의 발현을 추가로 포함한다.
본 발명에서 사용된 바와 같은 CEBPB(서열번호: 3)는 CCAAT 인핸서 결합 단백질 베타, CCAAT/인핸서 결합 단백질(C/EBP), 베타, 인터루킨 6-의존성 DNA-결합 단백질, CCAAT/인핸서-결합 단백질 베타, 인터루킨 6의 핵 인자, 전사 인자 5, 핵 인자 NF-IL6, TCF5, 간-강화 전사 활성인자(Liver-Enriched Transcriptional Activator) 단백질, CCAAT/인핸서 결합 단백질 베타, 간-강화 억제성 단백질, 전사 인자 C/EBP 베타, 간 활성인자 단백질, C/EBP-베타, C/EBP 베타, IL6DBP, NF-IL6, TCF-5, LAP 또는 LIP으로도 공지된 CCAAT 인핸서 결합 단백질 베타를 의미한다. 이 무인트론(intronless) 유전자는 기본 류신 지퍼(basic leucine zipper)(bZIP) 도메인을 포함하는 전사 인자를 코딩한다.
본 발명의 방법의 또 다른 실시양태에서, 방법은 전사 인자 RUNX1의 유전자의 코딩 서열(서열번호: 4)의 삽입 및 이의 발현을 추가로 포함한다.
본 발명에서 사용된 바와 같은 RUNX1(서열번호: 4)은 런트 관련 전사 인자(Runt Related Transcription Factor) 1, 런트-관련 전사 인자 1, 폴리오마바이러스 인핸서-결합 단백질 2 알파 B 서브유닛, SL3/AKV 코어-결합 인자 알파 B 서브유닛, SL3-3 인핸서 인자 1 알파 B 서브유닛, 급성 골수성 백혈병 1 단백질, 종양유전자 AML-1, PEBP2-알파 B, PEA2-알파 B, CBFA2, AML1, 코어-결합 인자 런트 도메인 알파 서브유닛 2 코어-결합 인자 서브유닛 알파-2, AML1-EVI-1 융합 단백질, 급성 골수성 백혈병, Aml1 종양유전자, CBF-알파-2, AML1-EVI-1, PEBP2알파, CBF2알파, PEBP2aB, AMLCR1 또는 EVI-1을 의미한다. 이 유전자에 의해 코딩되는 단백질은 CBF의 알파 서브유닛을 나타내며 정상적인 조혈의 발달에 관여하는 것으로 생각된다.
본 발명의 방법의 추가 실시양태에서, 방법은 전사 인자 IRF8의 유전자의 코딩 서열(서열번호: 5)의 삽입 및 이의 발현을 추가로 포함한다.
본 발명에서 사용된 바와 같은 IRF8(서열번호: 5)은 인터페론 공통 서열 결합 단백질 1, H-ICSBP, ICSBP1, ICSBP, IRF-8, 인터페론 공통 서열-결합 단백질, IMD32A, IMD32B 또는 인터페론 공통 서열-결합 단백질(ICSBP)로도 공지된 인터페론 조절 인자 8을 의미한다. 이는 인터페론(IFN) 조절 인자(IRF) 패밀리의 전사 인자이다.
본 발명의 방법의 또 다른 실시양태에서, 방법은 전사 인자 SALL1의 유전자의 코딩 서열(서열번호: 6)의 삽입 및 이의 발현을 추가로 포함한다.
본 발명에서 사용된 바와 같은 SALL1(서열번호: 6)은 아연 핑거 단백질 Spalt-1, 아연 핑거 단백질 SALL1, 아연 핑거 단백질 794, Sal-유사 단백질 1, ZNF794, Sal-1, 부고환 분비 단백질 Li 89, Spalt-유사 전사 인자 1, Sal(초파리)-유사 1, Sal-유사 1(초파리), HEL-S-89, HSAL1, HSal1, SAL1 또는 TBS로도 공지된 Spalt 유사 전사 인자 1을 의미한다. 이 유전자에 의해 코딩되는 단백질은 아연 핑거 전사 억제인자이며 NuRD 히스톤 데아세틸라제 복합체(HDAC)의 일부일 수 있다.
본 발명의 방법의 추가 실시양태에서, 전사 조절인자 단백질은 역 테트라시클린 전사활성인자(rtTA)(서열번호: 20)이고 이의 활성은 독시시클린 또는 테트라시클린에 의해 제어된다.
본 발명 내에서 사용된 바와 같이, 용어 "역 테트라시클린 전사활성인자(rtTA)"는 테트라시클린 또는 이의 유도체에 의해 유도된 전사 활성인자 단백질을 의미한다. 테트라시클린-제어 전사 활성화는 항생제 테트라시클린 또는 이의 유도체 중 하나(예를 들어, 보다 안정적인 독시시클린)의 존재 하에 전사가 가역적으로 켜지거나 꺼지는 유도성 유전자 발현 방법이다. 이 시스템에서, 전사 활성인자 단백질은 테트라시클린-반응성 전사 활성인자 단백질(rtTa) 또는 이의 유도체일 수 있다. 본 발명의 전사 조절인자 단백질은 rtTA일 수 있다. rtTA 단백질은 특정 TetO 작동자 서열에서 DNA에 결합할 수 있다. 이러한 TetO 서열의 몇몇 반복부는 함께 테트라시클린 반응 요소(TRE)(서열번호: 21)를 형성하는 최소 프로모터(예컨대 CMV 프로모터)의 상류에 배치된다. 테트라시클린 또는 유도체의 첨가가 rtTA 단백질을 활성화(Tet-On) 또는 탈활성화(Tet-Off)하는지에 따라, 이 시스템의 두 가지 형태가 있다. 독시시클린이 rtTA 단백질을 활성화시키는 Tet-ON 시스템은 또한 본 발명의 방법의 한 실시양태에서 사용될 수 있다.
Tet-On 시스템은 두 가지 구성요소로 구성된다:(1) 구성적으로 발현된 테트라시클린 - 반응성 전사 활성인자 단백질(rtTA) 및 rtTA 민감성 유도성 프로모터(Tet 반응성 요소, TRE). 이는 테트라시클린 또는 독시시클린(dox)을 포함한 이의 보다 안정적인 유도체에 의해 결합되어, rtTA가 활성화되어 TRE 서열에 결합하고 TRE-제어 유전자의 발현을 유도할 수 있다. 이를 사용하는 것이 본 발명의 방법에서 바람직할 수 있다. 따라서, 본 발명의 방법의 전사 조절인자 단백질은 외인성으로 공급되는 항생제 테트라시클린 또는 이의 유도체 중 하나에 의해 활성화 또는 탈활성화될 수 있는, 테트라시클린-반응성 전사 활성인자 단백질(rtTA)일 수 있다. 전사 조절인자 단백질이 rtTA라면, 제2 GSH 부위에 삽입된 유도성 프로모터에는 테트라시클린 반응 요소(TRE)를 포함한다. 외인성 공급 물질은 항생제 테트라시클린 또는 이의 유도체, 예컨대 독시시클린, 바람직하게는 테트라시클린 또는 독시시클린 중 하나일 수 있다.
변이체 및 변형된 rtTA 단백질이 본 발명의 방법에 사용될 수 있다. 이들은 Tet-On 어드밴스트(Advanced) 전사활성인자(rtTA2S-M2고도 공지됨) 및 Tet-On 3G(rtTA2S-S2에서 파생된 rtTA-V16으로도 공지됨))를 포함할 수 있다.
본 발명의 방법의 또 다른 실시양태에서, 유도성 프로모터는 Tet 반응성 요소(TRE)(서열번호: 21)를 포함한다.
본 발명 내에서 사용된 바와 같이, 용어 "Tet 반응성 요소(TRE)"는. 최소 프로모터와 함께, 스페이서 서열에 의해 분리된 19 bp의 7개의 반복부의 박테리아 TetO 서열을 의미한다. 최소 프로모터가 임의의 적합한 프로모터일 수 있기 때문에 TRE 서열의 변이체 및 변형이 가능하다. 바람직하게는, 최소 프로모터는 rtTA 결합의 부재 하에 발현 수준을 나타내지 않거나 최소 수준을 나타낸다. 따라서 제2 GSH에 삽입된 유도성 프로모터는 TRE를 포함할 수 있다. 본 발명의 기초가 되는 기본 유전적 원리는 또한 상이한 GSH 부위(hROSA26 및 AAVS1), 및 통합된 rtTA(서열번호: 20) 및 TRE(서열번호: 21)를 나타내는 도 2에 도시되어 있다.
본 발명의 방법의 추가 실시양태에서, 상기 제1 및 상기 제2 게놈성 안전한 하버 부위는 hROSA26 유전자좌(서열번호: 22), AAVS1 유전자좌(서열번호: 23), CLYBL 유전자(서열번호: 24), CCR5 유전자(서열번호. 25), HPRT 유전자(서열번호. 26) 또는 염색체 8 상의 부위 ID 325(서열번호: 27), 염색체 1 상의 부위 ID 227(서열번호: 28), 염색체 2 상의 부위 ID 229(서열번호: 29), 염색체 5 상의 부위 ID 225(서열번호: 30), 염색체 14 상의 부위 ID 259(서열번호: 31), 염색체 X 상의 부위 ID 263(서열번호: 32), 염색체 2 상의 부위 ID 303(서열번호: 33), 염색체 4 상의 부위 ID 231(서열번호: 34), 염색체 5 상의 부위 ID 315(서열번호: 35), 염색체 16 상의 부위 ID 307(서열번호: 36), 염색체 6 상의 부위 ID 285(서열번호: 37), 염색체 6 상의 부위 ID 233(서열번호: 38), 염색체 134 상의 부위 ID 311(서열번호: 39), 염색체 7 상의 부위 ID 301(서열번호: 40), 염색체 8 상의 부위 ID 293(서열번호: 41), 염색체 11 상의 부위 ID 319(서열번호: 42), 염색체 12 상의 부위 ID 329(서열번호: 43), 염색체 X 상의 부위 ID 313(서열번호: 44)을 가진 유전자로 이루어진 군으로부터 선택된다. 바람직하게는, 본 발명의 방법의 추가 실시양태에서, 본 발명의 방법의 추가 실시양태에서, 제1 및 제2 게놈성 안전한 하버 부위 hROSA26 유전자좌(서열번호: 22), AAVS1 유전자좌(서열번호: 23), CLYBL 유전자(서열번호: 24), CCR5 유전자(서열번호. 25), HPRT 유전자(서열번호. 26)로 이루어진 군으로부터 선택된다. 보다 바람직하게는, 제1 및 제2 게놈성 안전한 하버 부위는 hROSA26 유전자좌(서열번호: 22) 및 AAVS1 유전자좌(서열번호: 23)로 이루어진 군으로부터 선택된다.
천연 유전자 발현을 방해하지 않으면서 바이러스가 자연적으로 통합되는 부위를 찾아 추가 부위를 확인할 수 있다. 본 발명의 방법을 위해, 여러 GSH 부위가 사용될 수 있으며, 이는 하기에서 더 상세히 설명될 것이다.
아데노-연관 바이러스 통합 부위 1 유전자좌(AAVS1)(서열번호: 23)는 인간 염색체 19 상의 단백질 포스파타제 1, 조절 서브유닛 12C(PPP1R12C) 유전자 내에 위치하며, 이는 인간 조직에서 균일하고 편재적으로 발현된다. 이 부위는 AAV 혈청형 2에 대한 특이적 통합 유전자좌 역할을 하므로, 가능한 GSH로서 확인되었다. AAVS1은 침묵에 대한 유도성 카세트의 저항을 가능하게 하는 천연 염색체 절연체 및 개방형 염색질 구조를 포함하기 때문에 전사에 유리한 환경인 것으로 나타났다. PPP1R12C 유전자의 파괴로부터 생긴 세포에 대한 공지된 유해 효과는 없다. 게다가, 이 부위에 삽입된 유도성 카세트는 많은 다양한 세포 유형에서 전사적으로 활성을 유지한다. 따라서 AAVS1은 GSH로 간주되며 인간 게놈에서 표적화된 트랜스제네시스(transgenesis)에 널리 활용되었다.
hROSA26 부위(서열번호: 22)는 마우스로부터의 GSH(ROSA26 - 역 배향 스플라이스 수용체 부위 #26)와의 서열 유사성에 기초하여 확인되었다. 비록 오르토로그(orthologue) 부위가 인간에서 확인되었긴 하지만, 이 부위는 통상 유도성 카세트 삽입에 사용되지 않는다. 본 발명의 발명자들은 hROSA26 부위에 특이적으로 표적화 시스템을 사용하여 이 유전자좌에 유전적 물질을 삽입할 수 있었다. hROSA26 유전자좌(서열번호: 22)는 염색체 3(3p25.3) 상에 있으며, 앙상블(Ensembl) 데이터베이스(젠뱅크(GenBank):CR624523) 내에서 확인될 수 있다. 통합 부위의 정확한 게놈 좌표는 3:9396280-9396303: 앙상블이다. 통합 부위는 THUMPD3 긴 비-코딩 RNA(역 가닥)의 개방 판독 프레임(ORF) 내에 있다. hROSA26 부위가 내인성 프로모터를 갖기 때문에, 삽입된 유전적 물질은 상기 내인성 프로모터의 이점을 가질 수 있거나, 또는 대안적으로, 프로모터에 작동가능하게 연결되게 삽입될 수 있다.
염색체 13의 긴 아암 상에서 시트레이트 리아제 베타-유사(CLYBL) 유전자(서열번호: 24)의 인트론 2가 적합한 GSH로서 확인되었는데, 그 이유는 그것이 파지 유래된 phiC31 인테그라제의 확인된 통합 핫-스팟 중 하나이기 때문이다. 연구를 통해, 이 유전자좌에 무작위로 삽입된 유도성 카세트가 안정적이고 발현된다는 것이 입증되었다. 이 GSH에서 유도성 카세트의 삽입이 국부적 유전자 발현을 교란시키지 않는다는 것이 확인되었다(Cerbibi et al., 2015). 따라서, CLYBL은 본 발명에 사용하기에 적합할 수 있는 GSH를 제공한다
염색체 3 상에 위치하는(위치 3p2131) CCR5(서열번호: 25)는 HIV-1 주요 공동-수용체를 코딩하는 유전자이다. 유해 효과를 갖지 않는 것으로 보이나, HIV-1 감염 내성을 일으키기 쉬운 이 유전자에서 삭제 돌연변이로부터 이 부위를 GSH로서 사용하는 것에 대한 관심이 발생한다. 제3 엑손을 표적으로 하는 아연-핑거 뉴클레아제가 개발되었고, 따라서 이는 이 유전자좌에서 유전적 물질의 삽입을 허용한다. CCR5의 자연적 기능이 아직 밝혀지지 않았다는 점을 감안할 때, 그 부위는 추정 GSH로 남아 있으며, 이는 본 발명의 방법에서 사용될 수 있다. 히포크산틴-구아닌 포스포리보실 트랜스퍼라제(HPRT) 유전자는 퓨린 살비지 경로를 통한 퓨린 뉴클레오티드의 생성에서 중추적인 역할을 하는 트랜스퍼라제 효소를 코딩한다. 이는 GSH 부위로서 제기되었다. 이 부위에서의 삽입은 성숙 세포 유형에 대해, 예컨대 유전자 요법을 위한 변형에 대해 더욱 적용가능할 수 있다. 다른 유기체에서 GSH가 확인되었으며 마우스에서 ROSA26, HRPT 및 Hippll(Hll) 유전자좌를 포함한다.
포유동물류 게놈은 모조(pseudo) attP 부위를 기반으로 하여 GSH 부위를 포함할 수 있다. 이러한 부위위 경우, hiC31 인테그라제, 스트렙토마이세스(Streptomyces) 파지-유래된 레콤비나제가 attB 부위를 보유하는 유도성 카세트-함유 플라스미드를 모조 attP 부위에 통합시키는 능력을 갖기 때문에, 이는 비-바이러스성 삽입 도구로서 개발되었다. GSH는 또한 식물의 게놈에 존재하며, 식물 세포의 변형은 본 발명의 방법에서 사용될 수 있다. GSH는 벼의 게놈에서 확인되었다(Cantos et al., 2014).
하기 SHS 부위는 본 발명의 방법 중 어느 하나에서 사용될 수 있다. 이들은 문헌 [Pellenz et al., 2019]에 의해 공개되었으며, 상기에 기재된 9가지 기준 중 5가지를 충족한다: 염색체 8:68,720,172-68,720,191 상의 부위 ID 325(서열번호: 27); 염색체 1:231,999,396-231,999,415 상의 부위 ID 227(서열번호: 28); 염색체 2:45,708,354-45,708,373 상의 부위 ID 229(서열번호: 29); 염색체 5:19,069,307-19,069,326 상의 부위 ID 225(서열번호: 30); 염색체 14 :92,099,558-92,099,577 상의 부위 ID 259(서열번호: 31); 염색체 X 상의 부위 ID 263:12,590,812-12,590,831(서열번호: 32); 염색체 2:77,263,930-77,263,949 상의 부위 ID 303(서열번호: 33); 염색체 2:77,263,930-77,263,949 상의 부위 ID 317(서열번호: 60); 염색체 4:58,976,613-58,976,632 상의 부위 ID 231(서열번호: 34); 염색체 5:7,577,728-7,577,747 상의 부위 ID 315(서열번호: 35); 염색체 16:19,323,777-19,323,796 상의 부위 ID 307(서열번호: 36); 염색체 6:89,574,320-89,574,339 상의 부위 ID 285(서열번호: 37); 염색체 6:114,713,905-114,713,924 상의 부위 ID 233(서열번호: 38); 염색체 6:134,385,946-134,385,965 상의 부위 ID 311(서열번호: 39); 염색체 7:113,327,685-113,327,704 상의 부위 ID 301(서열번호: 40); 염색체 8:40,727,927-40,727,946 상의 부위 ID 293(서열번호: 41); 염색체 11:32,680,546-32,680,565 상의 부위 ID 319(서열번호: 42); 염색체 12:126,152,581-126,152,600 상의 부위 ID 329(서열번호: 43); 및 염색체 X:16,059,732-16,059,751 상의 부위 ID 313(서열번호: 44).
본 발명의 방법의 또 다른 실시양태에서, 상기 줄기 세포는 만능 줄기 세포, 유도 만능 줄기 세포(iPSC), 신경 전구 세포, 조혈 줄기 세포 또는 배아 줄기 세포(ESC)이다.
본 발명 내에서, 용어 "만능 줄기 세포"는 상기에 정의된 바와 같이 사용된다.
본 발명 내에서 사용된 바와 같이, 용어 "신경 전구 세포"는 만능 줄기 세포와 성숙한 체세포 사이의 만능 세포 상태를 의미한다. 이 세포 상태는 대개 뉴런, 희돌기교세포 및 성상교세포와 같은 특수화된 세포 유형이 되도록 결정된다.
본 발명 내에서, 용어 "유도 만능 줄기 세포(iPSC)"는 상기에 정의된 바와 같이 사용된다.
본 발명 내에서 사용된 바와 같이, 용어 "조혈 줄기 세포"는 조혈 줄기 세포를 의미한다. 이 특수한 유형의 만능 줄기 세포는 임의의 유형의 혈구를 형성할 수 있으나, 다른 세포 유형을 형성하는 능력을 상실하였다.
본 발명 내에서, 용어 "배아 줄기 세포(ESC)"는 상기에 정의된 바와 같이 사용된다.
본 발명의 방법의 추가 실시양태에서, 상기 줄기 세포는 인간 또는 마우스 줄기 세포이다.
본 발명 내에서 사용된 바와 같이, "인간 또는 마우스 줄기 세포"는 인간 또는 마우스로부터 유래된 세포를 의미한다. 그러나, 본 발명의 방법에 사용되는 줄기 세포는 임의의 인간 세포 또는 동물 세포일 수 있다. 그것은 바람직하게는 마우스 및 래트와 같은 설치류; 캥거루 및 코알라와 같은 유대목동물; 보노보, 침팬지, 여우원숭이, 긴팔원숭이 및 유인원과 같은 비-인간 영장류; 낙타 및 라마와 같은 낙타과; 말, 돼지, 소, 버팔로, 들소, 염소, 양, 사슴, 순록, 당나귀, 반텡, 야크, 닭, 오리 및 칠면조와 같은 가축 동물; 고양이, 개, 토끼 및 기니피그와 같은 가축으로부터의 세포와 같은 포유동물 세포이다. 세포는 바람직하게는 인간 세포이다. 특정 측면에서, 세포는 바람직하게는 가축 동물로부터의 것이다. 본 발명의 방법에 사용되는 세포의 유형은 일단 GSH 부위에 유전적 물질의 삽입이 완료되면 세포의 적용에 의존할 것이다. 본 발명의 방법에 사용되는 세포의 유형은 일단 GSH 부위에 유전 물질의 삽입이 완료되면 세포의 적용에 의존할 것이다.
본 발명은 또한 본 발명에 따른 방법 중 어느 하나에 의해 수득된 미세아교세포에 관한 것으로, 바람직하게는 여기서 미세아교세포는 ITGAM(CD11B)(서열번호: 45), ITGAX(CD11C)(서열번호: 46), CD14(서열번호: 47), CD16(서열번호: 48), ENTPD1(CD39)(서열번호: 49), PTPRC(CD45)(서열번호: 50), CD68(서열번호: 51), CSF1R(CD115)(서열번호: 52), CD163(서열번호: 53), CX3CR1(서열번호: 54), TREM2(서열번호: 55), P2RY12(서열번호: 56), TMEM119(서열번호: 57), 및 HLA-DR(서열번호: 58)로 이루어진 군으로부터 선택된 적어도 하나의 미세아교세포 표면 단백질을 발현한다.
따라서, 미세아교세포는 하기 표면 단백질 ITGAM(CD11B)(서열번호: 45), ITGAX(CD11C)(서열번호: 46), CD14(서열번호: 47), CD16(서열번호: 48), ENTPD1(CD39)(서열번호: 49), PTPRC(CD45)(서열번호: 50), CD68(서열번호: 51), CSF1R(CD115)(서열번호: 52), CD163(서열번호: 53), CX3CR1(서열번호: 54), TREM2(서열번호: 55), P2RY12(서열번호: 56), TMEM119(서열번호: 57), 및 HLA-DR(서열번호: 58) 중 적어도 하나를 발현함으로써 추가로 정의된다. 이들 단백질은 다음과 같이 정의된다.
본 발명에서 사용된 바와 같은 ITGAM(CD11B)은 인테그린 알파 M 쇄를 코딩하는 유전자인 인테그린 서브유닛 알파 M을 의미한다. 인테그린은 알파 쇄 및 베타 쇄로 구성된 이량체 통합 막 단백질이다. 이의 단백질 서열은 서열번호: 45에 주어진다.
본 발명에서 사용된 바와 같은 ITGAX(CD11C)는 인테그린 서브유닛 알파 X를 의미하고, 유전자는 인테그린 알파 X 쇄 단백질을 코딩한다. 이의 단백질 서열은 서열번호: 46에 주어진다.
본 발명에서 사용된 바와 같은 CD14는 단핵구 분화 항원 CD14를 의미하며, 이 유전자에 의해 코딩되는 단백질은 단핵구/대식세포에서 우선적으로 발현되는 표면 항원이다. 이의 단백질 서열은 서열번호: 47에 주어진다.
본 발명에서 사용된 바와 같은 CD16은, IgG 수용체 IIIa의 FCGR3A Fc 분획을 의미하며, 이 유전자는 면역글로불린 G의 Fc 부분에 대한 수용체를 코딩하고, 순환, 뿐만 아니라 다른 항체-의존성 반응으로부터 항원-항체 복합체의 제거에 관여한다. 이의 단백질 서열은 서열번호: 48에 주어진다.
본 발명에서 사용된 바와 같은 ENTPD1(CD39)은 엑토뉴클레오시드 트리포스페이트 디포스포히드롤라제 1을 의미하며, 이 유전자에 의해 코딩되는 단백질은 세포외 ATP 및 ADP를 AMP로 가수분해하는 원형질막이다. 이의 단백질 서열은 서열번호: 49에 주어진다.
본 발명에서 사용된 바와 같은 PTPRC(CD45)는 단백질 티로신 포스파타제 수용체 유형 C를 의미하며, 이 유전자에 의해 코딩되는 단백질은 단백질 티로신 포스파타제(PTP) 패밀리의 구성원이다. 이의 단백질 서열은 서열번호: 50에 주어진다.
본 발명에서 사용된 바와 같은 CD68은 CD68 항원을 의미하며, 이 유전자는 인간 단핵구 및 조직 대식세포에 의해 고도로 발현되는 110-kD 막관통 당단백질을 코딩한다. 이의 단백질 서열은 서열번호: 51에 주어진다.
본 발명에서 사용된 바와 같은 CSF1R(CD115)은 콜로니 자극 인자 1 수용체를 의미하며, 이 유전자에 의해 코딩되는 단백질은 대식세포의 생산, 분화, 및 기능을 제어하는 시토카인인 콜로니 자극 인자 1에 대한 수용체이다. 이의 단백질 서열은 서열번호: 52에 주어진다.
본 발명에서 사용된 바와 같은 CD163은 CD163 항원을 의미하며, 이 유전자에 의해 코딩되는 단백질은 스캐빈저 수용체 시스테인-풍부(SRCR) 슈퍼패밀리의 구성원이고 단핵구 및 대식세포에서만 독점적으로 발현된다. 이의 단백질 서열은 서열번호: 53에 주어진다.
본 발명에서 사용된 바와 같은 CX3CR1은 C-X3-C 모티프 케모카인 수용체 1을 의미하며, 이 유전자에 의해 코딩되는 단백질은 프랙트알킨에 대한 수용체이다. 이의 단백질 서열은 서열번호: 54에 주어진다. 프랙트알킨은 백혈구의 부착 및 이동에 관여하는 막관통 단백질 및 케모카인이다.
본 발명에 사용된 바와 같은 TREM2는 골수성 세포 2에서 발현된 촉발(Triggering) 수용체를 의미하며, 이 유전자는 TYRO 단백질 티로신 키나제 결합 단백질과 수용체 신호전달 복합체를 형성하는 막 단백질을 코딩한다. 이의 단백질 서열은 서열번호: 55에 주어진다.
본 발명에서 사용된 바와 같은 P2RY12는 퓨린성 수용체 P2Y12를 의미하며, 이 유전자의 생성물은 G-단백질 커플링된 수용체의 패밀리에 속한다. 이의 단백질 서열은 서열번호: 56에 주어진다.
본 발명에서 사용된 바와 같은 TMEM119는 단백질 코딩 유전자인 막관통 단백질 119를 의미한다. 이의 관련 경로 중에는 신경염증 동안 미세아교세포 활성화가 있다. 이의 단백질 서열은 서열번호: 57에 주어진다.
본 발명에서 사용된 바와 같은 HLA-DR은 주요 조직적합성 복합체, 클래스 II, DR 알파 및 베타를 의미하며 HLA-DRA 및 HLA-DRB1 둘 다는 HLA 클래스 II 알파 쇄 파라로그(paralogues)이다. 이의 단백질 서열은 서열번호: 58에 주어진다.
추가 실시양태에서, 본 발명은 또한 요법에 사용하기 위한 본 발명에 따른 미세아교세포를 포함한다.
본 발명에서 사용된 바와 같이, 용어 "요법"은 유기체, 동물 또는 인간의 질환 또는 원치 않는 건강 상태의 치료의 임의의 형태를 의미한다. 이는 또한 유전자 요법을 포함할 수 있다. 이는 치료 의도로 외래 DNA의 세포의 핵에 의도적인 삽입으로서 정의될 수 있다. 이러한 정의는 결함이 있는 유전자의 야생형 버전을 제공하기 위해 세포에 유전자 또는 유전자들의 제공, 표적 유전자 발현을 방해하는 RNA 분자에 대한 유전자의 추가(이는 결함이 있을 수 있음), 자살 유전자의 제공(예컨대 무해한 전구약물 간시클로비르(GCV)를 세포독성 약물로 전환시키는 효소 단순 헤르페스 바이러스, 티미딘 키나제(HSV-tk) 및 시토신 데아미나제(CD), 면역화 또는 암 요법(세포 입양 면역요법 포함)을 위한 DNA 백신 및 치료 목적으로 세포에 유전자의 임의의 다른 제공을 포함한다. 게다가, 성숙한 미세아교세포는 인간 또는 동물의 신체에 직접 이식하는데 사용할 수 있다. 대안적으로, 특정한 유전자와 약물의 상호작용 및 유전자 발현에 대한 약물의 효과를 포함한, 연구를 위한 시험 물질을 형성할 수 있다. 연구를 위한 미세아교세포는 해당 유전자 서열의 제어가능한 발현을 연구하기 위해, 알려지지 않은 기능의 유전자 서열을 가진 유도성 카세트의 사용을 포함할 수 있다. 게다가, 미세아교세포를 성장 인자 또는 시토카인과 같은 원하는 물질을 대량으로 생산하는데 사용할 수 있게 할 것이다.
추가로, 본 발명은 또한 한 실시양태에서 질환의 시험관내 진단을 위한 본 발명에 따른 이러한 미세아교세포의 용도에 관한 것이다. 바람직하게는, 질환은 바람직하게는, 질환은 중추신경계 질환, 바람직하게는 신경퇴행성 질환; 보다 바람직하게는 알츠하이머병, 파킨슨병, 전두측두엽 치매 또는 근위축성 측삭 경화증; 신경염증성 또는 자가면역 질환, 바람직하게는 다발성 경화증, 자가-항체-매개 뇌염 또는 감염성 질환, 신경혈관 질환; 바람직하게는 뇌졸중, 혈관염; 외상성 뇌 손상, 및 암의 질환으로 이루어진 군으로부터 선택된다.
추가로, 본 발명은 뇌 오르가노이드를 사용한 시험관내 배양을 위한 본 발명에 따른 이러한 미세아교세포의 용도에 관한 것이다.
본 발명 내에서 사용된 바와 같이, 용어 "오가노이드"는(대부분 줄기) 세포-유래 시험관내 3D-기관 모델을 의미하며, 본 발명에 따라 생성된 미세아교세포와 조합하여 뇌의 다른 세포와 미세아교세포의 관여 및 상호작용을 연구하기 위한 의학적 진단을 위한 강력한 도구를 나타낸다.
***
본원에서 사용된 바와 같이, 단수 형태 "a", "an", 및 "the"는 문맥이 명백하게 달리 나타내지 않는 한 복수 언급대상을 포함한다는 점에 유의한다. 따라서, 예를 들어, "시약"에 대한 언급은 이러한 상이한 시약 중 하나 이상을 포함하고 "방법"에 대한 언급은 여기에 기재된 방법을 변형하거나 대체할 수 있는 관련 기술분야의 통상의 기술자에게 공지된 동등한 단계 및 방법에 대한 언급을 포함한다.
달리 표시되지 않는 한, 일련의 요소 앞에 오는 용어 "적어도"는 상기 일련에서 모든 요소를 지칭하는 것으로 이해되어야 한다. 용어 "적어도 하나"는 특별히 상이하게 정의되지 않는 한, 하나 이상 예컨대 둘, 셋, 넷, 다섯, 여섯, 일곱, 여덟, 아홉, 열 또는 그 초과를 지칭한다. 관련 기술분야의 통상의 기술자는 단지 일상적인 실험을 사용하여 본원에 기재된 본 발명의 구체적 실시양태에 대한 많은 등가물을 인식하거나, 확인할 수 있을 것이다. 이러한 등가물은 본 발명에 포함되는 것으로 의도된다.
본원에 어디든지 사용되는 용어 "및/또는"은 "및", "또는" 및 "상기 용어에 의해 연결된 요소의 모두 또는 임의의 다른 조합"의 의미를 포함한다.
용어 "미만" 또는 차례로 "초과"는 구체적인 숫자를 포함하지 않는다.
예를 들어, 20 미만은 표시된 숫자 미만을 의미한다. 유사하게, "보다 많은" 또는 "보다 큰"은 표시된 숫자보다 많거나 큰 것을 의미하며, 예를 들어, 80% 초과는 80%의 표시된 숫자보다 많거나 보다 큰 것을 의미한다.
본 명세서 및 뒤따르는 청구범위 전체에 걸쳐, 문맥이 달리 요구하지 않는 한, 단어 "포함하다(comprise)", 및 변형 예컨대 "포함하다(comprises)" 및 "포함하는(comprising)"은 언급된 정수 또는 단계 또는 정수 또는 단계의 군의 포함을 함축하나, 임의의 다른 정수 또는 단계 또는 정수 또는 단계의 군의 배제를 함축하지는 않는다. 본원에서 사용되는 경우 용어 "포함하는"는 용어 "함유하는" 또는 "포함한(including)"으로 대체될 수 있거나, 또는 때때로 본원에서 사용되는 경우 용어 "갖는"으로 대체될 수 있다. 본원에서 사용되는 경우 "으로 이루어진"은 명시되지 않은 임의의 요소, 단계, 또는 성분을 배제한다.
용어 "포함한"은 "포함하나 이에 제한되지는 않는"을 의미한다. "포함한" 및 "포함하나 이에 제한되지 않는"은 상호교환적으로 사용된다.
용어 "약"은 플러스 또는 마이너스 10%, 바람직하게는 플러스 또는 마이너스 5%, 보다 바람직하게는 플러스 또는 마이너스 2%, 가장 바람직하게는 플러스 또는 마이너스 1%를 의미한다.
본 명세서의 설명 및 청구범위 전체에 걸쳐, 문맥이 달리 요구하지 않는 한 단수는 복수를 포함한다. 특히, 부정관사가 사용되는 경우, 명세서는 문맥에서 달리 요구하지 않는 한 단수뿐만 아니라 복수도 고려하는 것으로 이해되어야 한다.
본 발명은 본원에 기재된 특정한 방법론, 프로토콜, 재료, 시약, 및 물질 등에 제한되지 않고 따라서 다양할 수 있음을 이해하여야 한다. 본원에 사용된 용어는 단지 특정한 실시양태를 기재하기 위해 사용된 것으로, 단지 청구범위에 의해 정의되는 본 발명의 범위를 제한하려는 의도는 아니다.
상기 또는 하기에 상관없이, 본 명세서의 본문 전체에 걸쳐 인용된 모든 간행물(모든 특허, 특허 출원, 과학 간행물, 지침 등을 포함)은 그 전문이 본원에 참조로 포함된다. 본 명세서의 어떠한 내용도 본 발명이 선행 발명에 의해 이러한 개시내용보다 선행할 자격이 없다는 것을 인정하는 것으로 해석되어서는 안 된다. 참조로 포함된 자료가 본 명세서와 모순되거나 일치하지 않는 정도까지, 본 명세서는 이러한 모든 자료를 대체할 것이다.
본원에 인용된 모든 문서 및 특허 문서의 내용은 그 전문이 참조로 포함된다.
본 발명 및 이의 이점에 대한 더 나은 이해는 단지 예시적인 목적으로 제공된, 하기 실시예로부터 수득될 것이다. 실시예는 어떤 식으로든 본 발명의 범위를 제한하도록 의도되지 않는다.
발명의 실시예
하기 실시예는 본 발명을 예시하나, 본 발명의 범위를 제한하는 것으로 해석되어서는 안 된다.
실시예 1
재료 및 방법
초기 스크리닝 실험의 경우, 먼저 hROSA-CAG-rtTA hiPSC-라인(1개의 CAS9-닉카제, 2개의 hROSA26-특이적 가이드RNA(서열번호: 66 및 서열번호: 67)를 발현하는 3개의 플라스미드, 및 도 2A 및 도 4A에서 입증된 바와 같은 CAG-rtTA 발현 카세트: 항생제 선택, 클론 확장 및 개별 클론 hiPSC-콜로니의 특성화를 가진 공여자 플라스미드의 뉴클레오펙션(nucleofection)을 생성시켰고 4개의 AAVS1 표적화 벡터(서열번호: 61 내지 서열번호: 64)의 후속 일시적 형질감염(또한, 도 4B 내지 도 4E 참조)을 수행하여 단독으로 또는 바이-시스트로닉(bi-cistronic) 발현 카세트 형태의 3가지 다른 전사 인자 RUNX1(서열번호: 4), CEBPB(서열번호: 3), 또는 IRF8(서열번호: 5) 중 하나와 조합하여 PU.1(서열 번호 2)의 빠른 과발현을 가능하게 하였다(도 4B 내지 도 4E)(서열번호: 61 내지 서열번호. 64). 스크리닝 목적으로, 표적화된 세포는 클론 확장되지 않아, 세포의 서브세트에서만 과발현을 결과하였다.
놀랍게도, 초기 스크리닝 실험은 PU.1(서열번호: 2)에 더하여 다른 3개의 후보 리프로그래밍 인자를 발현하는 모든 3개의 세포주에서 골수 및 미세아교 세포 계통 마커의 신속한 유도를 입증하였으나, 야생형 대조군 hiPSC에서 또는 PU.1(서열번호: 2)만을 발현하는 세포에서는 아니다.
설명
프로토타입 프로토콜을 개발하고 적합한 판독 파라미터를 설정하기 위해, 본 발명자들은 PU.1(서열번호: 2) 및 CEBPB(서열번호: 3)의 조합 과발현에 초점을 맞추기로 결정하였다. 따라서, 완전히 검증된 이중 GSH 표적화된 유도성 PU.1 + CEBPB hiPSC가 생성되고 클론 확장되었다.
관찰
독시시클린의 첨가는 만능성(pluripotency) 마커 OCT4(서열번호: 78) 및 NANOG(서열번호: 79)의 발현의 급속한 손실 및 모든 세포에서 트랜스진 둘 다의의 유도를 결과하였다(도 6 참조).
실시예 2
재료 및 방법
간단히 말해서, hiPSC를 만능성 유지 배지에서 마트리겔(Matrigel)에 단일 세포로서 플레이팅하였다. 2일 후, 배지는 상기에 개요를 서술한 배아 사건의 순서를 모방하는 소분자 및 성장 인자와 함께 트랜스진 유도를 위한 dox가 보충된 둘베코 변형 이글 배지(DMEM)/F12로 바꾸었다. 유도 3일 후, 부착 세포는 조직 배양 플레이트에서 박리되기 시작하였고 상청액에서 부유하는 단일 세포로 발견되었다.
설명
후속적으로, 본 발명자들은 배지 조성의 최적화를 위해 최대 20일 동안 세포를 유도하는 더 긴 스크리닝 실험을 수행하였다. 다색 유세포 분석법은 원시 대식세포 및/또는 미세아교세포(CD11b(서열번호: 45), CD14(서열번호: 47), CD45(서열번호: 50), CD163(서열번호: 53), CX3CR1(서열번호: 54))의 유도를 위한 스크리닝 패널로서 선택된 골수 세포 표면 마커의 현저하게 강력하고 신속한 유도를 입증하였다. 본 발명자들은 또한 중요한 배양 조건-의존적 차이에 주목하였다: 전사 인자 과발현이 배아 발달의 순서를 모방하는 세포외 신호(cue)(소분자, 성장 인자)에 대한 적시 노출과 함께 수행될 때 가장 신속하고 효율적으로 유도가 발생하였다:(1)(후부 원시 선조) 배아외 중배엽 및 혈관모세포를 향한 만능 외배반(hiPSC)의 패턴,(2) 원시 조혈 및 초기 대식세포 전구체의 유도,(3) 원시 난황낭 대식세포로의 분화,(4) 미세아교세포로의 분화(도 5 참조).
관찰
세포는 유세포 분석법에 의해 입증된 바와 같이 CD45(서열번호: 50)(PTPRC로도 공지됨), CD11b(서열번호: 45)(ITGAM으로도 공지됨), CD14(서열번호: 47), 및 CX3CR1(서열번호: 54)를 포함한, 전형적인 골수성 표면 단백질을 신속하게 발현하기 시작하였다(도 5B 내지 도 5C 참조). 문헌 [Muffat et al., 2016]에 따르면, 10일까지, 모든 세포가 상청액으로 전이되고 최종적인, 화학적으로-정의된 미세아교세포 분화 및 유지 배지에서 폴리-L-리신(PLL) 코팅 조직 배양 접시 상에 아래로 플레이팅하였다. 흥미롭게도, 유도 프로토콜의 10일 후 독시시클린이 철회되었을 때 미세아교세포로의 분화가 훨씬 더 효율적으로 발생하여, 지속적인 트랜스진 발현으로부터 세포 표현형의 독립성을 명백히 입증하였다.
부착 배양에서 6-10일 간의 트랜스진이 없는 분화 및 성숙 후, 사실상 모든 세포는 유세포 분석법에 의해 정량화된 바와 같이(도 5C 참조) 또는 면역세포화학에 의해 입증된 바와 같이(도 5D 참조), CD39(서열번호: 49), P2RY12(서열번호: 56), TREM2(서열번호: 55), 및 TMEM119(서열번호: 57)를 포함한 매우 광범위한 공통 골수성 및 더 많은 미세아교세포 특이적 단백질을 발현하였다. 다음으로, 본 발명자들은 공동 배양 실험을 수행하였으며, 여기서 문헌 [Zhang et al., 2013], 및 [Pawlowski et al., 2017]에 따라 이전에 발표된 프로토콜에 따라 생성된 동종 hiPSC-유래 피질 뉴런의 순수 집단에 미세아교세포 전구체를 플레이팅하였다. 미세아교세포는 단독배양에서의 세포와 비교하여 더 분기화된(즉 덜 활성화된) 형태를 획득하였다(도 5E 참조). 단일 배양에서 hiPSC 및 미세아교세포의 실시간 qPCR 분석은 만능성 인자의 하향조절, MYB-독립성(미세아교세포의 원시 난황낭 대식세포 기원에 따라), 및 코어 미세아교세포 전사 인자, 통상적인 표면 마커, 및 최근 제안된 고유 미세아교세포 시그니처 유전자의 높은 발현 입증하였다(도 5F 참조).
참고문헌:
Figure pct00007
Figure pct00008
Figure pct00009
Figure pct00010
SEQUENCE LISTING <110> Westfaelische Wilhemlms-Universitaet Muenster <120> Rapid and deterministic generation of microglia from human pluripotent stem cells <130> UKM16706PCT <150> EP19176722.7 <151> 2019-05-27 <160> 87 <170> PatentIn version 3.5 <210> 1 <211> 810 <212> DNA <213> Homo sapiens <400> 1 atgttacagg cgtgcaaaat ggaagggttt cccctcgtcc cccctccatc agaagacctg 60 gtgccctatg acacggatct ataccaacgc caaacgcacg agtattaccc ctatctcagc 120 agtgatgggg agagccatag cgaccattac tgggacttcc acccccacca cgtgcacagc 180 gagttcgaga gcttcgccga gaacaacttc acggagctcc agagcgtgca gcccccgcag 240 ctgcagcagc tctaccgcca catggagctg gagcagatgc acgtcctcga tacccccatg 300 gtgccacccc atcccagtct tggccaccag gtctcctacc tgccccggat gtgcctccag 360 tacccatccc tgtccccagc ccagcccagc tcagatgagg aggagggcga gcggcagagc 420 cccccactgg aggtgtctga cggcgaggcg gatggcctgg agcccgggcc tgggctcctg 480 cctggggaga caggcagcaa gaagaagatc cgcctgtacc agttcctgtt ggacctgctc 540 cgcagcggcg acatgaagga cagcatctgg tgggtggaca aggacaaggg caccttccag 600 ttctcgtcca agcacaagga ggcgctggcg caccgctggg gcatccagaa gggcaaccgc 660 aagaagatga cctaccagaa gatggcgcgc gcgctgcgca actacggcaa gacgggcgag 720 gtcaagaagg tgaagaagaa gctcacctac cagttcagcg gcgaagtgct gggccgcggg 780 ggcctggccg agcggcgcca cccgccccac 810 <210> 2 <211> 270 <212> PRT <213> Homo sapiens <400> 2 Met Leu Gln Ala Cys Lys Met Glu Gly Phe Pro Leu Val Pro Pro Pro 1 5 10 15 Ser Glu Asp Leu Val Pro Tyr Asp Thr Asp Leu Tyr Gln Arg Gln Thr 20 25 30 His Glu Tyr Tyr Pro Tyr Leu Ser Ser Asp Gly Glu Ser His Ser Asp 35 40 45 His Tyr Trp Asp Phe His Pro His His Val His Ser Glu Phe Glu Ser 50 55 60 Phe Ala Glu Asn Asn Phe Thr Glu Leu Gln Ser Val Gln Pro Pro Gln 65 70 75 80 Leu Gln Gln Leu Tyr Arg His Met Glu Leu Glu Gln Met His Val Leu 85 90 95 Asp Thr Pro Met Val Pro Pro His Pro Ser Leu Gly His Gln Val Ser 100 105 110 Tyr Leu Pro Arg Met Cys Leu Gln Tyr Pro Ser Leu Ser Pro Ala Gln 115 120 125 Pro Ser Ser Asp Glu Glu Glu Gly Glu Arg Gln Ser Pro Pro Leu Glu 130 135 140 Val Ser Asp Gly Glu Ala Asp Gly Leu Glu Pro Gly Pro Gly Leu Leu 145 150 155 160 Pro Gly Glu Thr Gly Ser Lys Lys Lys Ile Arg Leu Tyr Gln Phe Leu 165 170 175 Leu Asp Leu Leu Arg Ser Gly Asp Met Lys Asp Ser Ile Trp Trp Val 180 185 190 Asp Lys Asp Lys Gly Thr Phe Gln Phe Ser Ser Lys His Lys Glu Ala 195 200 205 Leu Ala His Arg Trp Gly Ile Gln Lys Gly Asn Arg Lys Lys Met Thr 210 215 220 Tyr Gln Lys Met Ala Arg Ala Leu Arg Asn Tyr Gly Lys Thr Gly Glu 225 230 235 240 Val Lys Lys Val Lys Lys Lys Leu Thr Tyr Gln Phe Ser Gly Glu Val 245 250 255 Leu Gly Arg Gly Gly Leu Ala Glu Arg Arg His Pro Pro His 260 265 270 <210> 3 <211> 1038 <212> DNA <213> Homo sapiens <400> 3 atgcaacgcc tggtggcctg ggacccagca tgtctccccc tgccgccgcc gccgcctgcc 60 tttaaatcca tggaagtggc caacttctac tacgaggcgg actgcttggc tgctgcgtac 120 ggcggcaagg cggcccccgc ggcgcccccc gcggccagac ccgggccgcg cccccccgcc 180 ggcgagctgg gcagcatcgg cgaccacgag cgcgccatcg acttcagccc gtacctggag 240 ccgctgggcg cgccgcaggc cccggcgccc gccacggcca cggacacctt cgaggcggct 300 ccgcccgcgc ccgcccccgc gcccgcctcc tccgggcagc accacgactt cctctccgac 360 ctcttctccg acgactacgg gggcaagaac tgcaagaagc cggccgagta cggctacgtg 420 agcctggggc gcctgggggc cgccaagggc gcgctgcacc ccggctgctt cgcgcccctg 480 cacccaccgc ccccgccgcc gccgccgccc gccgagctca aggcggagcc gggcttcgag 540 cccgcggact gcaagcggaa ggaggaggcc ggggcgccgg gcggcggcgc aggcatggcg 600 gcgggcttcc cgtacgcgct gcgcgcttac ctcggctacc aggcggtgcc gagcggcagc 660 agcgggagcc tctccacgtc ctcctcgtcc agcccgcccg gcacgccgag ccccgctgac 720 gccaaggcgc ccccgaccgc ctgctacgcg ggggccgcgc cggcgccctc gcaggtcaag 780 agcaaggcca agaagaccgt ggacaagcac agcgacgagt acaagatccg gcgcgagcgc 840 aacaacatcg ccgtgcgcaa gagccgcgac aaggccaaga tgcgcaacct ggagacgcag 900 cacaaggtcc tggagctcac ggccgagaac gagcggctgc agaagaaggt ggagcagctg 960 tcgcgcgagc tcagcaccct gcggaacttg ttcaagcagc tgcccgagcc cctgctcgcc 1020 tcctccggcc actgctag 1038 <210> 4 <211> 1440 <212> DNA <213> Homo sapiens <400> 4 atggcttcag acagcatatt tgagtcattt ccttcgtacc cacagtgctt catgagagaa 60 tgcatacttg gaatgaatcc ttctagagac gtccacgatg ccagcacgag ccgccgcttc 120 acgccgcctt ccaccgcgct gagcccaggc aagatgagcg aggcgttgcc gctgggcgcc 180 ccggacgccg gcgctgccct ggccggcaag ctgaggagcg gcgaccgcag catggtggag 240 gtgctggccg accacccggg cgagctggtg cgcaccgaca gccccaactt cctctgctcc 300 gtgctgccta cgcactggcg ctgcaacaag accctgccca tcgctttcaa ggtggtggcc 360 ctaggggatg ttccagatgg cactctggtc actgtgatgg ctggcaatga tgaaaactac 420 tcggctgagc tgagaaatgc taccgcagcc atgaagaacc aggttgcaag atttaatgac 480 ctcaggtttg tcggtcgaag tggaagaggg aaaagcttca ctctgaccat cactgtcttc 540 acaaacccac cgcaagtcgc cacctaccac agagccatca aaatcacagt ggatgggccc 600 cgagaacctc gaagacatcg gcagaaacta gatgatcaga ccaagcccgg gagcttgtcc 660 ttttccgagc ggctcagtga actggagcag ctgcggcgca cagccatgag ggtcagccca 720 caccacccag cccccacgcc caaccctcgt gcctccctga accactccac tgcctttaac 780 cctcagcctc agagtcagat gcaggataca aggcagatcc aaccatcccc accgtggtcc 840 tacgatcagt cctaccaata cctgggatcc attgcctctc cttctgtgca cccagcaacg 900 cccatttcac ctggacgtgc cagcggcatg acaaccctct ctgcagaact ttccagtcga 960 ctctcaacgg cacccgacct gacagcgttc agcgacccgc gccagttccc cgcgctgccc 1020 tccatctccg acccccgcat gcactatcca ggcgccttca cctactcccc gacgccggtc 1080 acctcgggca tcggcatcgg catgtcggcc atgggctcgg ccacgcgcta ccacacctac 1140 ctgccgccgc cctaccccgg ctcgtcgcaa gcgcagggag gcccgttcca agccagctcg 1200 ccctcctacc acctgtacta cggcgcctcg gccggctcct accagttctc catggtgggc 1260 ggcgagcgct cgccgccgcg catcctgccg ccctgcacca acgcctccac cggctccgcg 1320 ctgctcaacc ccagcctccc gaaccagagc gacgtggtgg aggccgaggg cagccacagc 1380 aactccccga ccaacatggc gccctccgcg cgcctggagg aggccgtgtg gaggccctac 1440 <210> 5 <211> 1281 <212> DNA <213> Homo sapiens <400> 5 atgtgtgacc ggaatggtgg tcggcggctt cgacagtggc tgatcgagca gattgacagt 60 agcatgtatc caggactgat ttgggagaat gaggagaaga gcatgttccg gatcccttgg 120 aaacacgctg gcaagcaaga ttataatcag gaagtggatg cctccatttt taaggcctgg 180 gcagttttta aagggaagtt taaagaaggg gacaaagctg aaccagccac ttggaagacg 240 aggttacgct gtgctttgaa taagagccca gattttgagg aagtgacgga ccggtcccaa 300 ctggacattt ccgagccata caaagtttac cgaattgttc ctgaggaaga gcaaaaatgc 360 aaactaggcg tggcaactgc tggctgcgtg aatgaagtta cagagatgga gtgcggtcgc 420 tctgaaatcg acgagctgat caaggagcct tctgtggacg attacatggg gatgatcaaa 480 aggagccctt ccccgccgga ggcctgtcgg agtcagctcc ttccagactg gtgggcgcag 540 cagcccagca caggcgtgcc gctggtgacg gggtacacca cctacgacgc gcaccattca 600 gcattctccc agatggtgat cagcttctac tatgggggca agctggtggg ccaggccacc 660 accacctgcc ccgagggctg ccgcctgtcc ctgagccagc ctgggctgcc cggcaccaag 720 ctgtatgggc ccgagggcct ggagctggtg cgcttcccgc cggccgacgc catccccagc 780 gagcgacaga ggcaggtgac gcggaagctg ttcgggcacc tggagcgcgg ggtgctgctg 840 cacagcagcc ggcagggcgt gttcgtcaag cggctgtgcc agggccgcgt gttctgcagc 900 ggcaacgccg tggtgtgcaa aggcaggccc aacaagctgg agcgtgatga ggtggtccag 960 gtcttcgaca ccagccagtt cttccgagag ctgcagcagt tctataacag ccagggccgg 1020 cttcctgacg gcagggtggt gctgtgcttt ggggaagagt ttccggatat ggcccccttg 1080 cgctccaaac tcattctcgt gcagattgag cagctgtatg tccggcaact ggcagaagag 1140 gctgggaaga gctgtggagc cggctctgtg atgcaggccc ccgaggagcc gccgccagac 1200 caggtcttcc ggatgtttcc agatatttgt gcctcacacc agagatcatt tttcagagaa 1260 aaccaacaga tcaccgtcta a 1281 <210> 6 <211> 3975 <212> DNA <213> Homo sapiens <400> 6 atgtcgcgga ggaagcaagc gaagcctcaa catttccaat ccgaccccga agtggcctcg 60 ctcccccggc gagatggaga cacagaaaag ggtcaaccga gtcgccctac taagagcaag 120 gatgcccacg tctgtggccg gtgctgtgcc gagttctttg aattatcaga tcttctgctc 180 cacaagaaga actgtactaa aaatcaatta gttttaatcg taaatgaaaa tccagcctcc 240 ccacccgaaa ccttctcccc cagcccccct cctgataatc ctgatgaaca aatgaatgac 300 acagttaaca aaacagatca agtggactgc agcgaccttt cagaacacaa cggacttgac 360 agggaagagt ccatggaggt ggaggccccg gttgctaaca aaagcggcag cggcacttcc 420 agcggcagcc acagcagtac cgccccaagc agcagcagca gcagcagcag cagcagcggc 480 ggcggcggca gctcctccac aggtacctca gcgatcacaa cctctctacc tcaactcggg 540 gacctgacaa cactgggcaa cttctccgta atcaacagca acgtcatcat cgagaacctc 600 cagagcacca aggtggcggt ggcccagttc tcccaggaag cgaggtgcgg cggggcctct 660 gggggcaagc tggccgtccc agccctcatg gaacaactcc tagctctgca gcagcagcag 720 atccaccagc tgcaattgat cgaacagatt cgtcaccaaa tattgctgtt ggcttctcag 780 aatgcagact tgccaacatc ttctagtcct tctcaaggta ctttacgaac atctgccaac 840 cccttgtcca cgctaagttc ccatttatct cagcagctgg cagcagcagc tggattggca 900 cagagcctcg ccagccaatc tgccagcatt agtggtgtga aacagctacc cccaatccag 960 ctacctcaga gcagttctgg caacaccatc attccatcca acagcggctc ttctcccaat 1020 atgaacatat tggcagcggc agttaccacc ccgtcctctg aaaaagtggc ttcaagtgct 1080 ggggcctccc atgtcagcaa cccagcggtc tcatcatcgt cctcaccagc ttttgcaata 1140 agcagtttat taagtcctgc gtctaatcca cttctacctc agcaagcctc cgctaactcg 1200 gttttcccca gccctttgcc caacatcgga acaactgcag aggatttaaa ctccttgtct 1260 gccttggccc agcaaagaaa aagcaagcca ccaaatgtca ctgcctttga agcgaaaagt 1320 acttccgatg aggcattctt caaacacaag tgcaggttct gcgcgaaggt ctttgggagt 1380 gacagtgcct tgcagatcca cttgcgttcc cataccggag agaggccatt caagtgcaac 1440 atctgcggga acaggttctc caccaagggg aatctgaaag tccactttca gcgccacaaa 1500 gagaaatacc ctcatatcca gatgaacccc tatcctgtgc ctgagcattt ggacaatatc 1560 cccacgagta ctggcatccc atatggcatg tccatccctc cagagaagcc agtcaccagc 1620 tggctagaca ccaaaccagt cctgcctact ctgaccactt cagtcggcct gccgttgccc 1680 ccaaccctcc caagcctcat acccttcatc aagacggaag agccagcccc catccccatc 1740 agccattctg ccaccagccc cccaggctca gtcaaaagtg actccggggg ccctgagtca 1800 gccacaagaa acctaggtgg gctcccagag gaagccgaag ggtccactct gccaccctct 1860 ggtggcaaaa gcgaagagag tggcatggtc accaactcag tcccgacggc gagcagtagc 1920 gtcctgagct ccccagcggc agactgcggc cccgcgggca gtgccaccac cttcaccaac 1980 cctttgttgc cgctcatgtc cgagcagttc aaggccaagt ttccttttgg gggactcctg 2040 gactcagctc aggcatcaga gacgtccaag cttcagcaac tggtagaaaa cattgacaag 2100 aaggccactg accccaatga gtgcatcatc tgccaccggg ttctcagctg ccagagcgcc 2160 ttgaaaatgc actacaggac acacactggg gagaggccct ttaagtgtaa gatctgtggc 2220 cgggctttca ccacgaaagg gaatcttaaa acccactaca gtgtccatcg tgctatgccc 2280 ccgctcagag tccagcattc ctgccccatc tgccagaaga agttcacgaa cgctgtggtc 2340 ctgcagcagc acatccgaat gcatatggga ggccagatcc ccaacacccc agtccccgac 2400 agctactctg agtccatgga gtctgacaca ggttcctttg atgagaaaaa ttttgatgac 2460 ctagacaact tctctgatga aaacatggaa gactgtcctg agggcagcat ccctgataca 2520 cctaagtctg cagacgcctc ccaagacagc ttatcctctt cgcctttgcc cctcgagatg 2580 tcgagcatcg ctgctttgga aaatcagatg aagatgatca atgctggcct ggcagagcag 2640 ctacaggcca gcctgaagtc agtggagaat gggtccatcg agggggatgt cctgaccaat 2700 gattcatcct cagtgggtgg tgacatggaa agccaaagtg ctggcagccc agccatctca 2760 gagtctacct cttccatgca ggctctgtcc ccgtccaaca gcacgcagga gttccacaag 2820 tcacccagca ttgaggagaa accacagaga gcggtcccaa gcgagtttgc caatggtttg 2880 tctcccaccc cagtgaatgg tggggctttg gatttgacat ctagtcacgc agagaaaatc 2940 atcaaagaag attctttggg gatcctcttc ccttttagag accggggtaa atttaaaaac 3000 actgcttgtg acatttgtgg caaaacattt gcttgtcaga gtgccttgga cattcactat 3060 agaagtcata ccaaagagag accatttatt tgcacagttt gcaatcgtgg cttttccaca 3120 aagggtaatt tgaagcagca catgttgaca catcagatgc gagatctgcc atcccagctc 3180 tttgagccca gttccaacct tggccccaat cagaactcag cggtgattcc cgccaactcg 3240 ttgtcatctc tcatcaagac agaggtcaac ggcttcgtgc atgtttctcc tcaggacagt 3300 aaggacaccc ccaccagtca cgtcccgtct gggcctctgt cttcctctgc cacatcccca 3360 gttctgctcc ctgctctgcc caggagaact cccaagcagc actactgcaa cacatgtggc 3420 aaaaccttct cctcatcgag tgccctgcag attcacgaga gaactcacac tggagagaaa 3480 ccctttgctt gcactatttg tggaagagct ttcacgacta aaggcaatct taaggtacac 3540 atgggcactc acatgtggaa tagcacccct gcacgacggg gtcggcggct ctctgtggat 3600 ggccccatga catttctagg aggcaatccc gtcaagttcc cagaaatgtt ccagaaggat 3660 ttggcggcaa gatcaggaag tggggatcct tccagcttct ggaatcagta tgcagcagcg 3720 ctctccaacg ggctggcgat gaaggccaac gagatctccg tcattcagaa cggtggcatc 3780 cctccaattc ctggaagcct cggcagtggg aacagctcac ctgttagtgg gctgacggga 3840 aacctggaga ggctccagaa ctcagagccc aatgctcccc tggccggcct ggagaaaatg 3900 gcaagcagtg agaacggaac caacttccgc ttcacccgct tcgtggagga cagcaaggag 3960 atcgtcacga gttaa 3975 <210> 7 <211> 116 <212> PRT <213> Homo sapiens <400> 7 Gly Leu Glu Cys Asp Gly Lys Val Asn Ile Cys Cys Lys Lys Gln Phe 1 5 10 15 Phe Val Ser Phe Lys Asp Ile Gly Trp Asn Asp Trp Ile Ile Ala Pro 20 25 30 Ser Gly Tyr His Ala Asn Tyr Cys Glu Gly Glu Cys Pro Ser His Ile 35 40 45 Ala Gly Thr Ser Gly Ser Ser Leu Ser Phe His Ser Thr Val Ile Asn 50 55 60 His Tyr Arg Met Arg Gly His Ser Pro Phe Ala Asn Leu Lys Ser Cys 65 70 75 80 Cys Val Pro Thr Lys Leu Arg Pro Met Ser Met Leu Tyr Tyr Asp Asp 85 90 95 Gly Gln Asn Ile Ile Lys Lys Asp Ile Gln Asn Met Ile Val Glu Glu 100 105 110 Cys Gly Cys Ser 115 <210> 8 <211> 106 <212> PRT <213> Homo sapiens <400> 8 Lys Lys Asn Lys Asn Cys Arg Arg His Ser Leu Tyr Val Asp Phe Ser 1 5 10 15 Asp Val Gly Trp Asn Asp Trp Ile Val Ala Pro Pro Gly Tyr Gln Ala 20 25 30 Phe Tyr Cys His Gly Asp Cys Pro Phe Pro Leu Ala Asp His Leu Asn 35 40 45 Ser Thr Asn His Ala Ile Val Gln Thr Leu Val Asn Ser Val Asn Ser 50 55 60 Ser Ile Pro Lys Ala Cys Cys Val Pro Thr Glu Leu Ser Ala Ile Ser 65 70 75 80 Met Leu Tyr Leu Asp Glu Tyr Asp Lys Val Val Leu Lys Asn Tyr Gln 85 90 95 Glu Met Val Val Glu Gly Cys Gly Cys Arg 100 105 <210> 9 <211> 146 <212> PRT <213> Homo sapiens <400> 9 Pro Ala Leu Pro Glu Asp Gly Gly Ser Gly Ala Phe Pro Pro Gly His 1 5 10 15 Phe Lys Asp Pro Lys Arg Leu Tyr Cys Lys Asn Gly Gly Phe Phe Leu 20 25 30 Arg Ile His Pro Asp Gly Arg Val Asp Gly Val Arg Glu Lys Ser Asp 35 40 45 Pro His Ile Lys Leu Gln Leu Gln Ala Glu Glu Arg Gly Val Val Ser 50 55 60 Ile Lys Gly Val Cys Ala Asn Arg Tyr Leu Ala Met Lys Glu Asp Gly 65 70 75 80 Arg Leu Leu Ala Ser Lys Cys Val Thr Asp Glu Cys Phe Phe Phe Glu 85 90 95 Arg Leu Glu Ser Asn Asn Tyr Asn Thr Tyr Arg Ser Arg Lys Tyr Thr 100 105 110 Ser Trp Tyr Val Ala Leu Lys Arg Thr Gly Gln Tyr Lys Leu Gly Ser 115 120 125 Lys Thr Gly Pro Gly Gln Lys Ala Ile Leu Phe Leu Pro Met Ser Ala 130 135 140 Lys Ser 145 <210> 10 <211> 121 <212> PRT <213> Homo sapiens <400> 10 Ala Pro Met Ala Glu Gly Gly Gly Gln Asn His His Glu Val Val Lys 1 5 10 15 Phe Met Asp Val Tyr Gln Arg Ser Tyr Cys His Pro Ile Glu Thr Leu 20 25 30 Val Asp Ile Phe Gln Glu Tyr Pro Asp Glu Ile Glu Tyr Ile Phe Lys 35 40 45 Pro Ser Cys Val Pro Leu Met Arg Cys Gly Gly Cys Cys Asn Asp Glu 50 55 60 Gly Leu Glu Cys Val Pro Thr Glu Glu Ser Asn Ile Thr Met Gln Ile 65 70 75 80 Met Arg Ile Lys Pro His Gln Gly Gln His Ile Gly Glu Met Ser Phe 85 90 95 Leu Gln His Asn Lys Cys Glu Cys Arg Pro Lys Lys Asp Arg Ala Arg 100 105 110 Gln Glu Asn Cys Asp Lys Pro Arg Arg 115 120 <210> 11 <211> 165 <212> PRT <213> Homo sapiens <400> 11 Met Glu Gly Ile Cys Arg Asn Arg Val Thr Asn Asn Val Lys Asp Val 1 5 10 15 Thr Lys Leu Val Ala Asn Leu Pro Lys Asp Tyr Met Ile Thr Leu Lys 20 25 30 Tyr Val Pro Gly Met Asp Val Leu Pro Ser His Cys Trp Ile Ser Glu 35 40 45 Met Val Val Gln Leu Ser Asp Ser Leu Thr Asp Leu Leu Asp Lys Phe 50 55 60 Ser Asn Ile Ser Glu Gly Leu Ser Asn Tyr Ser Ile Ile Asp Lys Leu 65 70 75 80 Val Asn Ile Val Asp Asp Leu Val Glu Cys Val Lys Glu Asn Ser Ser 85 90 95 Lys Asp Leu Lys Lys Ser Phe Lys Ser Pro Glu Pro Arg Leu Phe Thr 100 105 110 Pro Glu Glu Phe Phe Arg Ile Phe Asn Arg Ser Ile Asp Ala Phe Lys 115 120 125 Asp Phe Val Val Ala Ser Glu Thr Ser Asp Cys Val Val Ser Ser Thr 130 135 140 Leu Ser Pro Glu Lys Asp Ser Arg Val Ser Val Thr Lys Pro Phe Met 145 150 155 160 Leu Pro Pro Val Ala 165 <210> 12 <211> 133 <212> PRT <213> Homo sapiens <400> 12 Ala Pro Met Thr Gln Thr Thr Ser Leu Lys Thr Ser Trp Val Asn Cys 1 5 10 15 Ser Asn Met Ile Asp Glu Ile Ile Thr His Leu Lys Gln Pro Pro Leu 20 25 30 Pro Leu Leu Asp Phe Asn Asn Leu Asn Gly Glu Asp Gln Asp Ile Leu 35 40 45 Met Glu Asn Asn Leu Arg Arg Pro Asn Leu Glu Ala Phe Asn Arg Ala 50 55 60 Val Lys Ser Leu Gln Asn Ala Ser Ala Ile Glu Ser Ile Leu Lys Asn 65 70 75 80 Leu Leu Pro Cys Leu Pro Leu Ala Thr Ala Ala Pro Thr Arg His Pro 85 90 95 Ile His Ile Lys Asp Gly Asp Trp Asn Glu Phe Arg Arg Lys Leu Thr 100 105 110 Phe Tyr Leu Lys Thr Leu Glu Asn Ala Gln Ala Gln Gln Thr Thr Leu 115 120 125 Ser Leu Ala Ile Phe 130 <210> 13 <211> 184 <212> PRT <213> Homo sapiens <400> 13 Pro Val Pro Pro Gly Glu Asp Ser Lys Asp Val Ala Ala Pro His Arg 1 5 10 15 Gln Pro Leu Thr Ser Ser Glu Arg Ile Asp Lys Gln Ile Arg Tyr Ile 20 25 30 Leu Asp Gly Ile Ser Ala Leu Arg Lys Glu Thr Cys Asn Lys Ser Asn 35 40 45 Met Cys Glu Ser Ser Lys Glu Ala Leu Ala Glu Asn Asn Leu Asn Leu 50 55 60 Pro Lys Met Ala Glu Lys Asp Gly Cys Phe Gln Ser Gly Phe Asn Glu 65 70 75 80 Glu Thr Cys Leu Val Lys Ile Ile Thr Gly Leu Leu Glu Phe Glu Val 85 90 95 Tyr Leu Glu Tyr Leu Gln Asn Arg Phe Glu Ser Ser Glu Glu Gln Ala 100 105 110 Arg Ala Val Gln Met Ser Thr Lys Val Leu Ile Gln Phe Leu Gln Lys 115 120 125 Lys Ala Lys Asn Leu Asp Ala Ile Thr Thr Pro Asp Pro Thr Thr Asn 130 135 140 Ala Ser Leu Leu Thr Lys Leu Gln Ala Gln Asn Gln Trp Leu Gln Asp 145 150 155 160 Met Thr Thr His Leu Ile Leu Arg Ser Phe Lys Glu Phe Leu Gln Ser 165 170 175 Ser Leu Arg Ala Leu Arg Gln Met 180 <210> 14 <211> 159 <212> PRT <213> Homo sapiens <400> 14 Met Glu Glu Val Ser Glu Tyr Cys Ser His Met Ile Gly Ser Gly His 1 5 10 15 Leu Gln Ser Leu Gln Arg Leu Ile Asp Ser Gln Met Glu Thr Ser Cys 20 25 30 Gln Ile Thr Phe Glu Phe Val Asp Gln Glu Gln Leu Lys Asp Pro Val 35 40 45 Cys Tyr Leu Lys Lys Ala Phe Leu Leu Val Gln Asp Ile Met Glu Asp 50 55 60 Thr Met Arg Phe Arg Asp Asn Thr Pro Asn Ala Ile Ala Ile Val Gln 65 70 75 80 Leu Gln Glu Leu Ser Leu Arg Leu Lys Ser Cys Phe Thr Lys Asp Tyr 85 90 95 Glu Glu His Asp Lys Ala Cys Val Arg Thr Phe Tyr Glu Thr Pro Leu 100 105 110 Gln Leu Leu Glu Lys Val Lys Asn Val Phe Asn Glu Thr Lys Asn Leu 115 120 125 Leu Asp Lys Asp Trp Asn Ile Phe Ser Lys Asn Cys Asn Asn Ser Phe 130 135 140 Ala Glu Cys Ser Ser Gln Gly His Glu Arg Gln Ser Glu Gly Ser 145 150 155 <210> 15 <211> 230 <212> PRT <213> Homo sapiens <400> 15 Asn Glu Pro Leu Glu Met Trp Pro Leu Thr Gln Asn Glu Glu Cys Thr 1 5 10 15 Val Thr Gly Phe Leu Arg Asp Lys Leu Gln Tyr Arg Ser Arg Leu Gln 20 25 30 Tyr Met Lys His Tyr Phe Pro Ile Asn Tyr Lys Ile Ser Val Pro Tyr 35 40 45 Glu Gly Val Phe Arg Ile Ala Asn Val Thr Arg Leu Gln Arg Ala Gln 50 55 60 Val Ser Glu Arg Glu Leu Arg Tyr Leu Trp Val Leu Val Ser Leu Ser 65 70 75 80 Ala Thr Glu Ser Val Gln Asp Val Leu Leu Glu Gly His Pro Ser Trp 85 90 95 Lys Tyr Leu Gln Glu Val Glu Thr Leu Leu Leu Asn Val Gln Gln Gly 100 105 110 Leu Thr Asp Val Glu Val Ser Pro Lys Val Glu Ser Val Leu Ser Leu 115 120 125 Leu Asn Ala Pro Gly Pro Asn Leu Lys Leu Val Arg Pro Lys Ala Leu 130 135 140 Leu Asp Asn Cys Phe Arg Val Met Glu Leu Leu Tyr Cys Ser Cys Cys 145 150 155 160 Lys Gln Ser Ser Val Leu Asn Trp Gln Asp Cys Glu Val Pro Ser Pro 165 170 175 Gln Ser Cys Ser Pro Glu Pro Ser Leu Gln Tyr Ala Ala Thr Gln Leu 180 185 190 Tyr Pro Pro Pro Pro Trp Ser Pro Ser Ser Pro Pro His Ser Thr Gly 195 200 205 Ser Val Arg Pro Val Arg Ala Gln Gly Glu Gly Leu Leu Pro His His 210 215 220 His His His His His His 225 230 <210> 16 <211> 128 <212> PRT <213> Homo sapiens <400> 16 Met Ala Pro Ala Arg Ser Pro Ser Pro Ser Thr Gln Pro Trp Glu His 1 5 10 15 Val Asn Ala Ile Gln Glu Ala Arg Arg Leu Leu Asn Leu Ser Arg Asp 20 25 30 Thr Ala Ala Glu Met Asn Glu Thr Val Glu Val Ile Ser Glu Met Phe 35 40 45 Asp Leu Gln Glu Pro Thr Cys Leu Gln Thr Arg Leu Glu Leu Tyr Lys 50 55 60 Gln Gly Leu Arg Gly Ser Leu Thr Lys Leu Lys Gly Pro Leu Thr Met 65 70 75 80 Met Ala Ser His Tyr Lys Gln His Cys Pro Pro Thr Pro Glu Thr Ser 85 90 95 Cys Ala Thr Gln Ile Ile Thr Phe Glu Ser Phe Lys Glu Asn Leu Lys 100 105 110 Asp Phe Leu Leu Val Ile Pro Phe Asp Cys Trp Glu Pro Val Gln Glu 115 120 125 <210> 17 <211> 210 <212> PRT <213> Homo sapiens <400> 17 Gln Val Gln Val Val Thr Gln Asp Glu Arg Glu Gln Leu Tyr Thr Pro 1 5 10 15 Ala Ser Leu Lys Cys Ser Leu Gln Asn Ala Gln Glu Ala Leu Ile Val 20 25 30 Thr Trp Gln Lys Lys Lys Ala Val Ser Pro Glu Asn Met Val Thr Phe 35 40 45 Ser Glu Asn His Gly Val Val Ile Gln Pro Ala Tyr Lys Asp Lys Ile 50 55 60 Asn Ile Thr Gln Leu Gly Leu Gln Asn Ser Thr Ile Thr Phe Trp Asn 65 70 75 80 Ile Thr Leu Glu Asp Glu Gly Cys Tyr Met Cys Leu Phe Asn Thr Phe 85 90 95 Gly Phe Gly Lys Ile Ser Gly Thr Ala Cys Leu Thr Val Tyr Val Gln 100 105 110 Pro Ile Val Ser Leu His Tyr Lys Phe Ser Glu Asp His Leu Asn Ile 115 120 125 Thr Cys Ser Ala Thr Ala Arg Pro Ala Pro Met Val Phe Trp Lys Val 130 135 140 Pro Arg Ser Gly Ile Glu Asn Ser Thr Val Thr Leu Ser His Pro Asn 145 150 155 160 Gly Thr Thr Ser Val Thr Ser Ile Leu His Ile Lys Asp Pro Lys Asn 165 170 175 Gln Val Gly Lys Glu Val Ile Cys Gln Val Leu His Leu Gly Thr Val 180 185 190 Thr Asp Phe Lys Gln Thr Val Asn Lys Gly Val Asp His His His His 195 200 205 His His 210 <210> 18 <211> 76 <212> PRT <213> Homo sapiens <400> 18 Gln His His Gly Val Thr Lys Cys Asn Ile Thr Cys Ser Lys Met Thr 1 5 10 15 Ser Lys Ile Pro Val Ala Leu Leu Ile His Tyr Gln Gln Asn Gln Ala 20 25 30 Ser Cys Gly Lys Arg Ala Ile Ile Leu Glu Thr Arg Gln His Arg Leu 35 40 45 Phe Cys Ala Asp Pro Lys Glu Gln Trp Val Lys Asp Ala Met Gln His 50 55 60 Leu Asp Arg Gln Ala Ala Ala Leu Thr Arg Asn Gly 65 70 75 <210> 19 <211> 112 <212> PRT <213> Homo sapiens <400> 19 Ala Leu Asp Thr Asn Tyr Cys Phe Ser Ser Thr Glu Lys Asn Cys Cys 1 5 10 15 Val Arg Gln Leu Tyr Ile Asp Phe Arg Lys Asp Leu Gly Trp Lys Trp 20 25 30 Ile His Glu Pro Lys Gly Tyr His Ala Asn Phe Cys Leu Gly Pro Cys 35 40 45 Pro Tyr Ile Trp Ser Leu Asp Thr Gln Tyr Ser Lys Val Leu Ala Leu 50 55 60 Tyr Asn Gln His Asn Pro Gly Ala Ser Ala Ala Pro Cys Cys Val Pro 65 70 75 80 Gln Ala Leu Glu Pro Leu Pro Ile Val Tyr Tyr Val Gly Arg Lys Pro 85 90 95 Lys Val Glu Gln Leu Ser Asn Met Ile Val Arg Ser Cys Lys Cys Ser 100 105 110 <210> 20 <211> 747 <212> DNA <213> Homo sapiens <400> 20 atgtctagac tggacaagag caaagtcata aactctgctc tggaattact caatggagtc 60 ggtatcgaag gcctgacgac aaggaaactc gctcaaaagc tgggagttga gcagcctacc 120 ctgtactggc acgtgaagaa caagcgggcc ctgctcgatg ccctgccaat cgagatgctg 180 gacaggcatc atacccactc ctgccccctg gaaggcgagt catggcaaga ctttctgcgg 240 aacaacgcca agtcataccg ctgtgctctc ctctcacatc gcgacggggc taaagtgcat 300 ctcggcaccc gcccaacaga gaaacagtac gaaaccctgg aaaatcagct cgcgttcctg 360 tgtcagcaag gcttctccct ggagaacgca ctgtacgctc tgtccgccgt gggccacttt 420 acactgggct gcgtattgga ggaacaggag catcaagtag caaaagagga aagagagaca 480 cctaccaccg attctatgcc cccacttctg aaacaagcaa ttgagctgtt cgaccggcag 540 ggagccgaac ctgccttcct tttcggcctg gaactaatca tatgtggcct ggagaaacag 600 ctaaagtgcg aaagcggcgg gccgaccgac gcccttgacg attttgactt agacatgctc 660 ccagccgatg cccttgacga ctttgacctt gatatgctgc ctgctgacgc tcttgacgat 720 tttgaccttg acatgctccc cgggtaa 747 <210> 21 <211> 350 <212> DNA <213> Homo sapiens <400> 21 gagtttactc cctatcagtg atagagaacg tatgaagagt ttactcccta tcagtgatag 60 agaacgtatg cagactttac tccctatcag tgatagagaa cgtataagga gtttactccc 120 tatcagtgat agagaacgta tgaccagttt actccctatc agtgatagag aacgtatcta 180 cagtttactc cctatcagtg atagagaacg tatatccagt ttactcccta tcagtgatag 240 agaacgtatg tcgaggtagg cgtgtacggt gggcgcctat aaaagcagag ctcgtttagt 300 gaaccgtcag atcgcctgga gcaattccac aacacttttg tcttatactt 350 <210> 22 <211> 1797 <212> DNA <213> Homo sapiens <400> 22 gctcgaaacc ggacggagcc attgctctcg cagagggagg agcgcttccg gctagcctct 60 tgtcgccgat tggccgtttc tcctcccgcc gtgtgtgaaa acacaaatgg cgtattctgg 120 ttggagtaaa gctcctgtca gttacgccgt cgggagtacg cagccgctta gcgactctcg 180 cgttgccccc tgggtggggc gggtaggtag gtggggtgta gagatgctgg gtgtgcgggc 240 gcggccggcc tcctgcggcg ggaggggagg gtcagtgaaa tcggctctgg cgcgggcgtc 300 ctcccaccct ccccttcctt cgggggagtc ggtttacccg ccgcctgctt gtcttcgaca 360 cctgattggc tgtcgaagct gtgggaccgg gcccttgcta ctggctcgag tctcacatga 420 gcgaaaccac tgcgcggggc gcgggggtgg cggggaggcg ggcgttggta cggtcctccc 480 cgaggccgag cgccgcagtg tctggccccg cgcccctgcg caacgtggca ggaagcgcgc 540 gctggaggcg ggggcgggct gccggccgag acttctggat ggcggcggcc gcggctccgc 600 cccgggttcc caccgcctga agggcgagac aagcccgacc tgctacaggc actcgtgggg 660 gtgggggagg agcgggggtc ggtccggctg gtttgtgggt gggaggcgct tgttctccaa 720 aaaccggcgc gagctgcaat cctgagggag ctgcggtgga ggaggtggag agaaggccgc 780 acccttctgg gcagggggag gggagtgccg caataccttt atgggagttc tctgctgcct 840 cccgtcttgt aaggaccgcc ctgggcctgg aagaagccct ccctcctttc ctcctcgcgt 900 gatctcgtca tcgcctccat gtcgagtcgc ttctcgatta tgggcgggat tcttttgcct 960 aggcttaagg ggctaacttg gtccctgggc gttgccctgc aggggagtga gcagctgtaa 1020 gatttgaggg gcgactccga ttagtttatc ttcccacgga ctagagttgg tgtcgaggtt 1080 attgtaataa gggtggggta gggaaatgga gcttagtcat tcacctgggg ctgattttat 1140 gcaacgagac tgcggattat cactacttat catttttgga gcatttttct agagacagac 1200 ataaagcatg atcacctgag ttttatacca tttgagaccc ttgctgcacc accaaagtgt 1260 agcatcaggt taaatcttaa tagaaaaatt ttagcttttg cttgagaaac cagtgcttcc 1320 ctccctcacc ctctctcccc aggctctcta cccctttgca tccctaccag gcatcttagc 1380 aactctcact catacttgat cccattttcc atttgttgta cttgctcctc tagtattcag 1440 acatagcact agctttctcc ctctcttgat cttgggtagc ctggtgtctc gcgaaaccag 1500 acagattggt tccaccacaa attaaggctt gagctggggc ttgactctta cccagcagtg 1560 cttttattcc tccctagttc acgttcttaa atgtttatct tgattttcat tttatccttt 1620 ttccttagct gggattctgt ccctgaccgt cttcacagtc caggtgatct tgactactgc 1680 tttacagaga attggatctg aggttaggca acatctccct ttttcttcct ctaaatacct 1740 ctcatttctg ttcttaccag ttagtaactg atctcagatg cctgtgtgat agcttcc 1797 <210> 23 <211> 1642 <212> DNA <213> Homo sapiens <400> 23 tgctttctct gacctgcatt ctctcccctg ggcctgtgcc gctttctgtc tgcagcttgt 60 ggcctgggtc acctctacgg ctggcccaga tccttccctg ccgcctcctt caggttccgt 120 cttcctccac tccctcttcc ccttgctctc tgctgtgttg ctgcccaagg atgctctttc 180 cggagcactt ccttctcggc gctgcaccac gtgatgtcct ctgagcggat cctccccgtg 240 tctgggtcct ctccgggcat ctctcctccc tcacccaacc ccatgccgtc ttcactcgct 300 gggttccctt ttccttctcc ttctggggcc tgtgccatct ctcgtttctt aggatggcct 360 tctccgacgg atgtctccct tgcgtcccgc ctccccttct tgtaggcctg catcatcacc 420 gtttttctgg acaaccccaa agtaccccgt ctccctggct ttagccacct ctccatcctc 480 ttgctttctt tgcctggaca ccccgttctc ctgtggattc gggtcacctc tcactccttt 540 catttgggca gctcccctac cccccttacc tctctagtct gtgctagctc ttccagcccc 600 ctgtcatggc atcttccagg ggtccgagag ctcagctagt cttcttcctc caacccgggc 660 ccctatgtcc acttcaggac agcatgtttg ctgcctccag ggatcctgtg tccccgagct 720 gggaccacct tatattccca gggccggtta atgtggctct ggttctgggt acttttatct 780 gtcccctcca ccccacagtg gggccactag ggacaggatt ggtgacagaa aagccccatc 840 cttaggcctc ctccttccta gtctcctgat attgggtcta acccccacct cctgttaggc 900 agattcctta tctggtgaca cacccccatt tcctggagcc atctctctcc ttgccagaac 960 ctctaaggtt tgcttacgat ggagccagag aggatcctgg gagggagagc ttggcagggg 1020 gtgggaggga agggggggat gcgtgacctg cccggttctc agtggccacc ctgcgctacc 1080 ctctcccaga acctgagctg ctctgacgcg gccgtctggt gcgtttcact gatcctggtg 1140 ctgcagcttc cttacacttc ccaagaggag aagcagtttg gaaaaacaaa atcagaataa 1200 gttggtcctg agttctaact ttggctcttc acctttctag tccccaattt atattgttcc 1260 tccgtgcgtc agttttacct gtgagataag gccagtagcc agccccgtcc tggcagggct 1320 gtggtgagga ggggggtgtc cgtgtggaaa actccctttg tgagaatggt gcgtcctagg 1380 tgttcaccag gtcgtggccg cctctactcc ctttctcttt ctccatcctt ctttccttaa 1440 agagtcccca gtgctatctg ggacatattc ctccgcccag agcagggtcc cgcttcccta 1500 aggccctgct ctgggcttct gggtttgagt ccttggcaag cccaggagag gcgctcaggc 1560 ttccctgtcc cccttcctcg tccaccatct catgcccctg gctctcctgc cccttcccta 1620 caggggttcc tggctctgct ct 1642 <210> 24 <211> 291666 <212> DNA <213> Homo sapiens <400> 24 ctcggcgttc tcaccgctgc agaacggctg cagggggcag agtaaagagc tgctgtcagt 60 ttccctgccc agagagtgcc aacagctgct ctgacctatt gcaggcatgt gtgttccagg 120 atgcagcctt cctgcacttt gaccactcta gattaattgc taaccaagat atgcacatga 180 tggggctcac aaagtattag gcggtatttt aacaacaaaa gctgcgaaga aatccctaga 240 aatgttggct cttctggctg ggaaaacgca gtctgtcaac agttgcctca aaaactcaga 300 agctcagaga gttggattcg gtcaccagag aggcccctca aagaggcccc aaccattcag 360 atcctctgct ctgtccccca tgacagcggg gacgaaggtc ctaagccctg gccgggaggg 420 cagttgacct cgggactcgc cgcggggcgg agcgggtgct gggaggaagg agggcgtggc 480 tggcggggtg tggctggcgg gacggggcgg ggcgaagaca gagcgaggcg gggcctggga 540 cggggggggg gtcggtgtcg ccgtgggggc gtggaatgtg gggtgggcgt ggctaaaggc 600 aaagggcggg gcgcgcgcgt cgggaagatg gcgctacgtc tgctgcggag ggcggcgcgc 660 ggagctgcgg cggcggcgct gctgaggctg tgagtgcagg tccccgttcc ccgccttccc 720 ggcccggctc gccgcgggtc ggctcctgtt gcagccccgc gggccgggcg cggcctcccc 780 aagccctcac gggaacccag ccggacggaa gcaccatgcg cctcccacgc gctggctcga 840 cctcgtccaa ggtcgctgcc gcccgcgcct ccctttggga gggccctcgt tgcacccgga 900 aaatgggtac acaccttagg tcgaattacc tggactcagc cccaggaaac aaaactgcct 960 gcctccccca aatggcaaac gtgaacgcgc cagtctttga gaggcggctt gcctggtgaa 1020 gaacacctgc ggttcgttta acacagcggt tcccaaacgg tttggtctca ggacccgttt 1080 acacgtctaa aaataatttg aggacccccc aaagcttttg cttatatcta ttgatttttg 1140 tgcatgagga attaaaccag aaatttaaaa aatattcact taataacaaa cccattaact 1200 tttaatacaa ataacacttt aatgcataac ttctcaaaaa aaaagtgaga agattggctc 1260 atggttttta tatttttgaa aatttctttg gtttaataaa ggacagctgg agtctcatat 1320 cagctgtttt gaaggaaata tttgaaagaa attctgggct catgcagatg cagatattag 1380 ttgggaaagg gaggaccaag cagaccctct caacgggtct cagggacccc ctcaggtgtc 1440 tttggaccac actttgagaa ccgctggtct agcacttgcc catcgcctag gtacgtgcac 1500 atacatggtc tcatttggtt cccttgacca ccatgtgaag aagttgggtg tcatgtttat 1560 aaagatgaaa aaacagggtc agaaaggtta aggattctca aagccctatg accagtaatg 1620 agagagtttg gttcaaacac taagtgtatg gctcctggtc tggaacttct ttatttattt 1680 atttttattt tttgagacag agtctcggtc tgtcacctag gctgtagtac agtggtgtaa 1740 tctcggctta ctgcaacctc cacctcctgg gttcaagcga ttctcatgcc tcagcctcct 1800 gagtggctgg cattacaggt gtgcaccacc acccctggct aatttttgta tttttagtag 1860 agacagagtt tcgccatgtt ggccaggctg ttctcgaact cctgacctca agggggtcca 1920 cccggatcag cctcccaaag tgctgggatt acaggcgtga gccaccatgg ccggcctggt 1980 ggtctggaac ttcttttttt tttttttttt ttttttttcc gagatggagt ttcgcttttg 2040 tcgcccaggc tggagtgcaa tggcgccatc tcagctgact gcaacctccg cctcccggat 2100 tcaagtgatt ctcctgccgc agcctccgga gtagttggga ttacagggcg tccgccacca 2160 tgcccggcta atttttgtat ttttaataga gacgaggttt caccatgttg gccaggctgg 2220 tctggagctc ctgacctcgg gtgatccacc tgcctcggcc tcccaaagtg ttgggattaa 2280 aggcgtgagc caccgtgccc ggcctgggtc tgaacttctt acgtcttctt gcactgtgac 2340 tcttcagtca cccatgtcct atgggaggac ccacctagtc ttatgcatcc cactttccca 2400 tttcctccgc tgcccctggc acaggggagt cacccctcgc cctagaggag cagctcaggc 2460 agtgtatcca ggctggtcca gaagggtcct tttctggcgc cttttgaggg ggccagcgtc 2520 tgtgacctgt tcagtagcgg gtccagtgag cgcacacagt ccccacgcca gtacgctggg 2580 ggttaactca gtgctcctca cccgccttag cacactggtc tgttctcgac atgtctaccc 2640 gctgaatata ggattcttga ttggcatttt ttttcctttg agcattttaa agcgtattat 2700 cgcactgtct ttttgcctcc attattctaa tgagaattca gacgttaatg ttattagggt 2760 tctatgtaag tgatgagtct tttttttttt tttttttttt ttttttttgc ttgattttct 2820 ctttgtcttg gtctttcggt ggttttatta tgatgtgtgt agatctgttt gagtttatcc 2880 tcttggaagt ttattgagtt tcttggatgt gtatacatca aatttgggaa gtttttggct 2940 attgttctct caaaaaagtc tactctctta tctctctctt ctctttcgga ggctcccatt 3000 gcgtatatgt tggtgtagtt gatggaaccc cacaggtctt tgagactgtt ccattttctt 3060 tctgttcctc aggctggaca atgtcaattg acctgtcttt gttttttttt tttttttttt 3120 tttttttgag acagagtctt gctctgtcac caggctggag ttcagtggcg caatttctgc 3180 ccactgcaac ctctgactcc cgggttcaag cgattctcct gctccagctt cccgagtagt 3240 tgggattaca ggcacgcgcc accacgtcca gctaattttt gtatttttag tagagacggg 3300 gtttcaccat gttggccagg atggtctcga tcttctgacc tcgtgatcca cctgccttgg 3360 cctcccaaag tgctgggatt acaggtgtga gccaccgtgc ccagccgacc tgtttttagg 3420 tttgctgatt gctccgtctt ccaactcaaa tcattttcat tttaatccag aacttctttc 3480 tttttggaga atgagtctca ctctgtcacc caggctggag tgcagtggtg caatctgggc 3540 tcactacaac ctctgcctcc tgggctcaag ctgtcctccc acctcagcct cccaaatagc 3600 tgggactaca ggtgtgcacc actgcacctg gctaattgtt tctattcttt tgtagaaatc 3660 aggtttcgcc atgttgctca ggctggtctc gaacttggct caagcaatct gcctgcctct 3720 gtcgctcata gtattgggat tacaggcatg agccatcatg cccggccctt ttctatactt 3780 tctatctctt cattgatatt ctctatgtac tgaaacatcg ttctcatact ttcctttagt 3840 tctttttttc tttctttctc ttagagacgg agtctccagg ctggagtgca gtggtgagat 3900 cgtagctcac tgcagcctgc agctcctggg ctcaagtgat cctcctgcct cagcctcccc 3960 agtagctggg actacaggca cacaccacta tgcccagcta atttttaaat tttttgaaga 4020 gacagagtct tgcagtgttg ccaagggtgg tcttgaactg ctgggttcaa atgattttct 4080 tgccttggcc tccaaagcag tggaattcta ggcatgaacg actgcacctg gactccttca 4140 gttctttatg catagtttcc tttcgttttt tgaacatact ttaaatagat gatttaatta 4200 gtaagtccaa catctggact tcctcaggga cagtttgtac tgactacttt tttcctgtgt 4260 gtataggtca tactttcttt tcgttgcatg tcttgtatat ttttttgaaa actggacatt 4320 ttaagtaata taatggggca actctggaaa tcagatttct cccttttgcc agggtttatt 4380 gttgttgttg tttgcttagt gactttaata aactaattct gcattgtatt ctttgtcatg 4440 tgcaaccagc gaggtctctg cttggttagc ttagtagtct aacaattaga caaaggtttc 4500 cttaaattcc tggaaccagt aagtctccta gtctttgctg agggactctg tgtgtgtcag 4560 gacatgtctt caacattcag ccacagtttg tcctgcttcc acagagactg aaggttagct 4620 agacatgagc acttaaggtc tttccttagc cggtatacag ccctgcacat gtgcgtggcc 4680 tcctagagtc tcaggaacat gtcacaactt ttcagagctc tctatgggta tcttgttctc 4740 catttttgcc ttttaagtgt tttggttagc ctgttgttta ccctgttatc ttccatctca 4800 agtagctgtg atggtaaata agtacttctg attgtttgga caaatgccct ccgggaaaat 4860 actgttccca ctgtgcaagc tctgagtcag gtcaattaaa gacagtttta caagtagggt 4920 cttccaagga accacaagac aggtcaaata gtgacatttt ccagaaatgg ggctttcccc 4980 ctctagtggc tgccatgctg ctggttttca ctgtgatggg ggctattgat tttcaagtct 5040 accacagagc tggggaagag ggatagggta aactaaaccc ccacgacaat tgctgttctt 5100 actgagattc atacattttt cttgaataaa tgatccctat attgctgcaa gtctttaatt 5160 tctagaattc tgaaaaagtt tattctgaca atttttgcca atattcttgt tgattttatg 5220 gaggatagga ttttcaaagg tcctttttct gtagtttttg ctgaagtcag cctgcataga 5280 gttttgatcg agtggatttg aatttataaa tttttttttg catctgttgt gttgatcata 5340 aggcttttct tcttcagtgt gttaatacgg taaattacag tgattgactt tttaaaagtt 5400 aagctgacca ttgcattcct ggaataaacc ccactgattg tgatgtattg tttggattgc 5460 atgtgctaaa attttgttaa aattatttgt atctgtgttc ataaggaata atcgcctata 5520 gttttctgat attgccttgg tctgggtttg gtattaggat ggtgatggtc acataggatg 5580 tgttggagag ttcccgcttc tatttcatga aacaatttgt gtaaatttgg taagattttg 5640 cctgtaaatg tttgcacctg cagttttctt tgtggaaaaa gtgttaaact acaaatttag 5700 tttctttaat agacatattg ccattcagat tatctagttc ttcttgagta agctttggta 5760 gtttgtatct ttgaaggact atgtccattt catctaagtt gtcacattca cgtgcctgga 5820 gttgttcatg ctgactcctt atcctttttc ttacagctct acaaaggtat ataccacaca 5880 attcaccctt tgtaagtgtg tgattaaata atttctagta agtttatagg cccatcacta 5940 cagtccaatg ttaggccccc ctccaaattt ctatcatccc gcaaattctc ttgagcccat 6000 ttgcagttaa tccttacccc tgcctctagt ctgtcatctc cttactgttt gtgtcatcca 6060 tagtgatgtg tccttcttca tccttgatat ttgtaattct tttttctctg ttttttattt 6120 tatcacctgg cttgagttat tttgctcttt ttaaagaacc atctttttgt tttatcgatt 6180 tttctctttt ttttgttttc tatttcattg atttctgtct catctttatt atttcctacc 6240 ttcaccttac tttgggttta atttaccctt taccttttta aggtggaaat ttagataatt 6300 aattttagac ctttctactt tttttttttt tttttttgag acaaggtctt gctctgtcac 6360 ccaggctgga gtgcactgat gcaatcttgg ctcactgcaa cctccacatt ctaagctcaa 6420 acagtcctcc tgcctcagcc tcccaagtag ctgagactac aggcattagc caccatgtct 6480 ggctaatttt tgtatttttt ggagagacgg ggtttcgcca tgttgcccag gcttgtctca 6540 aactcctgga ttcaagcagt ctacccacct tggcctccga aagtgctggg attatggatg 6600 tgagccgcca cacccatccg gggtctactt tctaaatata agcactcagt aattacttta 6660 cagccatgct tggtggctca tgtctataat cccagcactt tgaaaggctg aggtgggagg 6720 atcacttgtg gccaggagtt caagtccaga ttgggtaaca tagtgagatg ctgtcactac 6780 aaaaaaaatt ttaaaagtta gctggatgtg gtggctcatg cctgtgatcc tagccacttg 6840 ggatgctgag gtgggaggat tccttgagcc tggggatttg gggtttcagt gagctgtgat 6900 gataccactg cactccagcc tgggtgacag agcaaagctc tattaaaaat agtgatgata 6960 ataataataa taataataat aataataata ataataacaa aattccctct aaggattgtt 7020 ttaattccct ctagcaaatt ttgcaagatt tctgatacct gtaatctctt ttcatttctt 7080 atgttgatac tctgtttctg ttttctaaag tattcatagt aagactccaa aagaaaaagg 7140 gctccctggc tgtatgtgtt cagtggtagc agccaaggaa tgtgccagga aggtacttca 7200 cattttgcag tgccgtggtg gagaggaatc tggtaaagaa aaaaccagat gaagacagtt 7260 tagagaggcg acaactacaa gctaagtacc tgagattctg ggtcaacagg aaggggacag 7320 tgtgtgagga agcagcaggg ccatggaagg tggctgaggg gcctggatgg ggttacctgt 7380 cagggtccca ataggccttt tgtagggttg gcttcatctt tgaagcctcc tgaggttacc 7440 gtgacaacca ctactgtccc tctgtactgc tgtgaggcca ctaagggaaa aagggaggga 7500 agggacccaa agggaggaca gaggtgggag aagagggagc gatggggaga gaaaggcaga 7560 gaacaatgga agcagtgagc gagaaagggg agaaacctca ctgaaaagga ggcagggtaa 7620 acatgactga gatggaaaaa tgatcacatt aaaaagaact cactcagagt aaggatgaat 7680 gtgtgttctt tgctacttga actggtatta aaaggccaat gtgaagtgtt agatatttta 7740 aaatgtttat tggtatcatt agaagttgac ttcagttgcc caaatgcatg gtgagaaagg 7800 ggatgtgtaa acaaaaatga tattttggat tgtgaggcag aaagtcattt taaatggccc 7860 tgggaggcag agggcccaat cctctcagtc gcctgggact gtcctgggtt tagcatggaa 7920 tgccttatgt tcccagaaac cccttaggtc ccagcaaacc aggatggcca ttcaccatag 7980 aggtggagaa gtaaagggct gtggatgaag acgggtactt attaggaaca gggaggagga 8040 tggagttgga ggggatgagt gcagggcagg atacagagcc cagaaggaaa ggaattgaca 8100 gaagctggga gaaagaataa aaagaccagt ggtccaagat ggtagaccac aggttcaaga 8160 actggagcaa gagtcttctg gaatggcctc cattctagaa ccgagagaga gtattcagaa 8220 tgctttaatg gagtaagaag ggccactgct tagagtgggg ctgaagagaa aagaaagaag 8280 gagaccctgc ggaagcggca ataccaggaa ggcagttgta tgcacatcat gcagaccagg 8340 agtagcctag gggtagggga catgcctggg ctggacagtg gaatttgtgg gaaatcagat 8400 ttccctgagc aaaaaccagt gggcagcagc caaactggtg agcaagaact ggctgtggtg 8460 gctgggcccg aattgggagc tacacctgcc cgggcaggtg tagctgcgag ggaggtctct 8520 gccaacaact cagctgtgcc gtgcctgctg aacggcctca ccttggcctc tggctctgtt 8580 gcagctgtgt ggggctcgtg ctcctacata ccgttatcct gtggtagagt tttaccgtgg 8640 accagagcca tctagaggac attgagttac ccacatactt tctgtgggag aggccaagga 8700 gtcagggggg gaggccggga cctgaagatc aactctttac tgcagagatc cctccctccc 8760 tctctctgtc ccatggatcc agagggaagt tgaggacagt ttcatgccac atgcttgacc 8820 cgactcaact gagtaactgt ggccactgag aagactctgt ccttgcaaat aactctcctt 8880 agtgcccata ttctgcagaa tgtttgagtg gcacgagtac ttcattcgtc tagaaatatt 8940 tcatggtagt cagttgctaa taacaggata tctgcaggta gtgtgttctc aggaggcaca 9000 cctgaagcct caaaggtgag gacatagaca tggctgtggg tgagcctgtg ccaagacatg 9060 acccatatcc atggggagtg ctctcagggc agctgacact gctcagcctc agcagtctcc 9120 agtgatagct tcggaacagc cacggtctga ctgatatact ttctgaaaac agcctttggt 9180 cacacagttt cctaactaaa tgtggtggtg gccactagaa gttgccattt tatgcgggac 9240 tccctgtgag gaagcccata gtgctggtag ctgaaattta ggaatgcagg tttctaagaa 9300 ggctcggaaa agcaagctgg gctccttggg gaggagctat tagtacgttt aattaaattt 9360 tttaacatat aaaaagttgt taattataaa aacaacattt ttttctaccc tgagtgcagc 9420 tggagctgtg ttctgccgtt acacaattcc tcattaattc cacacattgc ttacgatcct 9480 gtgaagttta gaattttatt aggcaataaa taagaaatca aggaaataat atttgtggtt 9540 tcatatcggt cacttgggta tgaatttaaa tccactgtaa ttcaaacagg tttagtttat 9600 ttcatgttgc tacttgaatg tgttatagcg tatcaattaa ataactcact tgaatgatgc 9660 agacttgaga ttcattccct ccttctttcc ttccttcctt tctcacccca tcctccctac 9720 cataaaccag gtttagaata gctgttaatt tagctgcttt gattttttgt tgttgtttat 9780 tttgaaacgg agtctcactc tgtcgctcag gctggagtgc agtggcacaa tctcagctca 9840 ctgcaacctc tgcctcctgg gttcaagcga tcctcctgcc tcagcctcct gagtagctgg 9900 aattacaggt gcacaccacc acgcacagct aattttttta tttttatttt ttatttttag 9960 tagagatggg gtttcaccat gttggtcagg ctggtcttga actcctggcc tcgtgatctg 10020 cctgccttgg tctcctgaag tgctgggatt ataggtgtga gccaccacgc ctggcttttt 10080 tttttttttt ttttttttta agactggtga agctatgttg cccagactgg actgcagtgg 10140 ctattcgcag gtgttatcat agcttactgc agccttgaca tcctgggcac cagtagcgct 10200 tcttcctcag tctctagtag ctgggactgc aggcatgtgc taccacaccc agctgatttt 10260 atgttttgtt tacatttaac gatgttaatc taggagcagt gatgatgttc actgttgttc 10320 cacatgactc tagcacatat atatttgtat gtgtataacc acagttgttc atttagtctg 10380 tttccaggtt ttcatttagt ctgttccagg ttcatttagt ctgtttccag acctaaaaag 10440 gcctgttggc taccgcgaca gccttggctg tcacactggg cccgcccatg ggtgtttctg 10500 taagtggcca tgaacctctt ctgaactaca ccacatgtta acatccttct cttagttagg 10560 tctttgagat tggcagaggt gctctattta ataataaagg aatgggctgg gcattggtgg 10620 ctcacacctg taattccagc actttgagag gctgaagtgg accgatcact tgaggtcaga 10680 agttcaagac cagcctggcc agcatggtga aaccccgtct ctactaaaaa tacaaaaatt 10740 agcctggtgt ggttgcgcat gcctgtagtc ccagctactc aggagactga ggcaggagaa 10800 ttgcttgaac ccaggaggtg gaggttgcag tgagccaaga tcatgccact gcactccagc 10860 ctgggtgaca gagcgcgact ccgtctcaat aataataata atagtaataa taataatata 10920 ataaaggaat gaaagtttcc ttagaaagta aggtttctat tttaatagaa tacttgagtg 10980 agcaagtctg tcttaactgt ttctcctcac tgtgtctaaa tgagaaggaa gaatgaccct 11040 ggtgtctgta tttgcaggac acttttcagt attaatattc agaaccccaa atattgaaaa 11100 gtgtaaaagg cagtacttgc tacttcattg tcccgttgct agccccagta aaatgagggt 11160 cttagtttag cggaagactg tgtttactgt ttaactcaca gttcacgcta aaaattggca 11220 cttttttttt tcctaataag ggcctctcta tggacctttt taaagtttat atggtcatta 11280 aaaacatcat tgcacacata tactttgtac cactttggaa gtagtgcagg cttgtttgaa 11340 agcatacact tgacttgtct tcttacttag tctcacagta ttctttgtga gaaggttgat 11400 atgcccacat tattctgtgg ccaaaaacaa aagtttagga aatgaaaaca gcaaacagaa 11460 aaccccatgc caagtgctgt tttcgtagtg aggcactgga gggcgctccg ctctagcaat 11520 gggagatgca cgcagtctct gcagtctgca ggctgccctc acgaacgcct ttcagaagat 11580 gtaagagttt tttctgttca ttttaaggca aatgaaagac acatggatgg tagaggaaat 11640 atttctatac tgacctataa acggtccctt taaaagttta tgagaaactg aagaagtagc 11700 tctgtgctcc agccctcctt atgacctcct ctctccctag cctgttgcag cctcaccggc 11760 ctcctcttct gggctgtgtc gtcagcctga agccctctgt ccctttgtgc ctcagctcaa 11820 atgtcacaaa tcagagaggt cttccttgac caccctgtac aacatagcct ccaccccgct 11880 aagcagcctc tgcactaccc tgtcccctta ctgctgtttt cattttttcc tattgcccca 11940 tttccaccag acatatcaca tgcttatttg tttattgtcc gcctgtatcc taccccagcc 12000 cccagatatt catgagagca gggacttggt ttattccatt gctactatat atccagaacc 12060 taaaacaatc cttggcagtg cctgatataa atttgcagaa ggaaaaaaga acagatttag 12120 gaatgaaata ttttgagtgt ttctaaagat ttagtggatt ttttttcttt attttggtaa 12180 attatacata acaaaattat cattttaact tttttttttt tgaggtggag tctagctctg 12240 cccccaggct ggagtgcagt ggtgcgatct cactcactgc aacctctgcc tcctgggttc 12300 aagcaactct cctgcctctg cctccgagta gctgggatta caggtgcccg ccaccacgcc 12360 tggctaattt tttgtatttt tagtagagac ggggtttcac catgttggcc aggctggtct 12420 cgaactcctg acctcaggtg atctacccgc ctcggcctcc caaagtgctg ggattacagg 12480 cgtgagccac catggccggc ccattttaac catctttaag tgtacagttt agtggcatta 12540 agtacattca cattgttgta caactgtcac caccatccat cttcagaact tttttatctt 12600 cccacactga aaccctgtgc ccattaaaca ctaactccct gttcccttcc ccccacccag 12660 cccctggtaa ccaccattct cattattttc actgtgaatt tgactactct aggtacttca 12720 catacataga ctcacatatt tgtccttttg tgtttggctt atttcactca gcataatatc 12780 ttccaaggtg catccatgtt acagcaggta tctgattttc attcattttt aaggctgaat 12840 aatctattgt gtgcctattc catattttat ttatccatcc atctgttgat ggacatttga 12900 gtatcactgc caccttttgg ctattgttag tgcatgttct atgtggagca cagaaatgtg 12960 atgtttaagt ttaagcctaa agtggatttc tttgaattat actagccagt cacagatcac 13020 tcctgggtag tactatggtt tgaatgtggt atcccctcca aaattcatgt tgaaacttaa 13080 ttcccattgt ggtggtatta agaagtgggg ccttgtagga agtggttaag tcatgagggc 13140 tgtgcctcat gaatgggtta gtatcattgg aaagaggctt cagagagagt tttccagtct 13200 tgcccttcca ccctgcgcca tgtgaggaca cagcaataag gcgccatatt ggaagcagag 13260 agcagccctc tgtagacacc aaggctggca ccttgatctt agattcccca gcctccagaa 13320 ctgtgggaag taagtttctg ttgtttataa attagcccag tgtgtaatac tttttaaaat 13380 agcagcataa acagactaag acaggtggtt tctactttta ggaaaatatt tttagttcat 13440 attaagatag aaacttattc tagctcctaa aaatcagaat tgttttaata tcctcaggtg 13500 ctctttaatt ttttcttaca attgtcaaaa acaagtttaa aatcaagtta ctaactctgc 13560 tataggcagg aagctcctgg atagatactc tggggttcaa gtccaatgct gacccgcagt 13620 tggcccttga ccttgttcaa ggcccttatc tagattgtgc cttatttttc tcacccatca 13680 aaaggaggat ggacaagttt cttcctgcca gttgacattc cagagtctag aaaggaatta 13740 ttgccctcaa gtaagacgac cttggggaat tcagaaataa aaagtatata gctttttgag 13800 ctctaagtta ttttggtcca tttgagctca atttgaccag agattgaaga taaaagctct 13860 gcctccccca aacttattgg tacagcctgc actcaattgg ttttaccgcc ttctcctgac 13920 attaagggag atgtttttgg ttgtgtggtg ttgacccttt aggtcctcag aaggggcggc 13980 accctcatgg tgtctctgcc tgcagcaggg agtgctacca ggcactttgt tccagtgact 14040 tatgatggac acagcacagc gcctaggggt taggattcta aaataattca ggtgtatgga 14100 gacgcagaac ctaaaagaac tcaggagaaa gagaaggtag atatcctaaa ttttagtctg 14160 attttgactc agaagtggat acctgatttt ggcctacatt tcacctcttt cagttttttt 14220 ctgctccatt tgggttccct gctcacttgg aaccctcaag ctggcttgca aatgcccaga 14280 gccacagtgc tctcataggg tctgcctgtt ctagggccca tcagccagca gtccagcagg 14340 gatgaccagt gagcccaaga aaacaagcag tgctgatgtc agatgtgtag cccttctcaa 14400 gtgctataca ttttaagaaa tgccttcact gggcatggtg gctcatgcct gtaatcccag 14460 cactttggga ggccaagatg ggcggatcac gaggtcagga gttggagacc aacctggcac 14520 aacatgataa aaccctgtct ctactaaaaa tacaaaaatt agctgaacgt ggtggtcaca 14580 cacctctaat ctcagctact caggaggctg aggcaggaga atcgcttaaa cccggaaggt 14640 ggaggttgca gtgagctgag atcctgccat tgcactccag cctgggtgac agtgagactc 14700 tgtctcaaaa aaagaaagaa agaaaaagag agagagagaa agagagagag agagagaaag 14760 aaagaaagaa aaagaaagaa agaaaaaaga aagaaaatgt cttcttcaga cacctcaact 14820 acaaaggagt cagccagtca agagaatttc tcctctacca ggaagagaat atgggtatag 14880 gagaagcttg gagtctctct gccacccctc atgttctctg gacaaagtcc caagctgtgc 14940 gtttgaatca tcagtgtcta cttgtcctgc agaacatcag gaatttacca ggtaatctgg 15000 tgacatgcct gcaccagagg actgggagaa tccttaccgt taaacctctt ctccccaccc 15060 ctgaacacat aaatacactt tttaagcttc ctaacgctgt actctgatca tggtgcccac 15120 ccccttggac agcataaatt tcccagtgac ctccaattac ctgccgctaa agtccaggcc 15180 ccttagtgtg gcatgtacgc acctcctcac ctatcctcca tctttccatt tccccccagg 15240 ccgcttacct gtggcccaca tgcaccactc accatgcccc acactctcga gtcatcagtg 15300 ccacttcctc ctggaagcct tctttccctg gacacctcag ccagccatct gtctcgtccc 15360 tgagagccct aacctctccg ctgacttttg tcacccttcc ctgtgttaag gtgatcgaga 15420 tgcagaactc ccagtggtct ttgatgcctc ctctcctctc ccacccacac cccatctgtt 15480 gccaggcctg ttgattttcc ccttcaggtg ccaactcttc tttcattgta ttagtttcct 15540 attgctgttg taacagatta tcgcaaacat ggtggtttaa attaagcttg tccctgcagc 15600 ctgtgggcca catgtgacct gggatgactt tgaatacgac ccaacacaaa tttgtgagct 15660 ttcttaaaac atgagatttt ttggcgattt tttttttttt ccctttagct tatcagctgt 15720 tgttagtgga ttttatgtgt ggtccaagac aattcttctt ccagtgtggg gccagggaag 15780 ccaaaaaaac tggacaccct tggttaagtt aacacagatt tgttaactta tgcttctgca 15840 gtttggaagt ctgacctagg ttttgtgggc tgaaaccaag gtgtttacag ggatggagag 15900 tgttctttct ggcagttcta ggggtgatct gtttgcttgc ctgtttcagc ttctagaggc 15960 tgcccacatt ctttggctca tggctcctta tccatcttca aagccagacc cagtgggctg 16020 aattcttctc cccattgctg ccatctctcg ggttctgttg cttctgccac ccttttccac 16080 ttagaagcac ccttgtgatt acgttggccc cacctggata accagggcca gtcgccccaa 16140 ctcagggtca gctgattagc aaccttcatt ccactttgcc atgtaacctg acatatcaat 16200 aaatactggg tataaggacg tggacatctt tgggggccat tattctgcat acccatccac 16260 tgttatagat tcaggtttga actcttggaa tgaccatcta atgggctgag ttccctcatt 16320 gcctctcatg ttatgtgctg ccagcataga tattaagatg tacattctat catctagacc 16380 tgttggttcc aaaaacatct cttggatctg tccttttctt tttgtctcca ttgcccctac 16440 cctagtggca aacaatcctg tgaaaaagga ttgtttacat gtatgggtgc ccctccaggc 16500 aatattcaag tgtactcttc gaggctgttt tagtacattc accatattgt gcaaccatca 16560 cctccatcta gttccaaaac attttcatcg ccctaaagga gaactctatc cattgagcgg 16620 ccattcccca ttccctcctc tcctcaaccc ctggcaacca ccagtctgtc ttctgtctct 16680 gtgcatttac cattcctttg tatggatata gcactacatt ttgtttattt tttaaattaa 16740 atttaatttt ttagagacag gatgtagctc tgtcatccag gttggagtat agtggcaccg 16800 tcacccaggc tggagtgtag tggcatgatc atagctcact gtagccttgg actcctgggc 16860 ttgagtgatt ccccctgcct caaccttcca agtagctagg actgcaggca cccaccacca 16920 cacctggctc attttttaaa tttatttgtc agttgatgga catttgggct gtttccactt 16980 tttggtgatt gtgactagtg ctgctatgaa cattcatata caggtatttg ttttcagttc 17040 ctttaggttt atacctagga actgctgtgc catatagtaa ttctatgttt aactttttga 17100 ggaaccacca aactgttttc cacagtggct gcaccatttt acattccacc agcaatgtac 17160 aagcgttctg atttctccac atcctcgcca acacttgcta ttttccattg tttttattgc 17220 agccatccta gtagatgtga agttgtattc tcgcggtttc ttccaaatca tttttaaatg 17280 tacaaattgt ctaatttcac ttctctgctt cacatccttc ctattgcatt tataataaac 17340 cctggccccc atcttggact ccaaggagta tatgatcttc tccctcctac ctctttctct 17400 cactgccttc catgctcctc actcagtcca cttaccgagc atcattggcc ttctcctgtt 17460 ccctcaagca gggaaggcaa acacccatgg gcttttattt attatttctt tatttatttt 17520 ttaacacttc cctccttagg tccagagacc atgggctttg aggctcaggg gattcagatc 17580 caaggtccat ttagaagtaa atgatgagat gagttgggca ctgtggctca cgcctgtaat 17640 tagcactttg ggaggccgag gtgggcagat catgaggtca ggagatcgag actatcctgg 17700 ctaatacagt gaaaccccat ctctactaaa aattcaaaaa attagccggg catggtggtg 17760 catacctgta atcccagcta ctcgggaggc tgaggcagga gaatcgcttt aacctgggag 17820 gtgaaggttg cagtgagccg agatcgtgcc actgcactcc agcctgggca acagagtgag 17880 actccatctc aaaaaaaaaa aaaaaaaaag atgagatgat gcattgaatg ctaggtatgg 17940 cgtgtatgta gttcataaga acaccaataa acagtggatg taaaaagcaa catcagatag 18000 atacctaaag gccatgtctt tggaacaggg gtaaccacct gaagcatgtc ctcccttccc 18060 tgcctttttc ctccctcaga gcaccccgtt cttcattgca cttatgattt gtcaccagcc 18120 acgaatgtgt gcatctccct gttatgtttg gtctcctgca ctgggctgga aactccacgt 18180 tcacccttta tgcctgtgcc cagcacagtg cctgacacag taggcactga ttaaatgatt 18240 cttgaatgac tgcatcatca tatggtcaca gtaaacagaa tccatcacta attatctatt 18300 tgacatgagc gggtggaaag gcaaagtttt tatgcatgag tgtgggtgta tgtatgtttt 18360 cctagattat agatttgtct aaacattcct gctaatttta agatatcaaa tctgaagttt 18420 ccttggcttg aatttttgaa cataggccaa ggttgttttt agattcctca gtattctctc 18480 ttttgtgaaa gttttcaaaa gtataaacgg cgcatcttcc gtacaactgg tttacattgt 18540 tggtttatgc agttgagttg tgggcagagg ggaaacctca atgtctgaat gtggctttac 18600 cccagcgctg agatatcccc gggagagctt ggccagtctg agtccatgtg gcctaaagat 18660 cctccctagc cagttccctg tcccacctac attctgttta tttcagaact tctcacctgt 18720 tgaacacaca gcccttcctc aacacaggac cagctcagca tcgggaagct gtattttaag 18780 aaaatcatgg tcttccagct cagtggaggc atcttagcgg gatccaaaat aacattcgct 18840 tttatcttga aattctttct gtttttggtt tttccccaac tctcatcctt cccccacctt 18900 cacctcagac actccaggtt attactgaaa ttaagcatga tagaaagtgt ggactcatag 18960 gctcagttct gttccctcct tatggccagc gtgtggaaga gctcctctgc tctcatgcct 19020 tctccatcgg agctggttca tcaccttggc ctgtcttggg cggagtcccc gacttgggag 19080 ttgtgctgtt cgtttgctgt ccatcgggct gtaagctcct tgaggaccag gcaccatgtt 19140 tactcacccc tgtcccttct gggaacctgg gggaaactgc taactggcgt ggctctcaga 19200 ccttgcatgg ccccacacat tttttttctg tgggaaccac taagcattag caactcgcca 19260 gtgatcagca gggattagca gcgtttaggc tccgcagaca tttaatgtgc taattgagga 19320 gcccagggtt cggccaagga agtgatttac aaaggtggaa acgggactgt tgacacaggt 19380 gcatcttatt aattactggt ttggggaatt agtaaaaatg ttaataattt gagggattat 19440 tgttaatgaa ggataagaaa cttcacaacc atatggttta ctacttgatg cgattttccc 19500 ttttttaaaa aaatactttt aaatctgggt tttaggaagg acaagccatt tcttgcagaa 19560 cttattgatt gtattacata ggtaaatgga aaaatatttc ctagaacaat tttttgtaac 19620 agaaaattct aaaacatacc agtagtatga agtaagaggc acctatggca catctttgta 19680 ttattcagtc cctcctttat acattcttct gacaagaacg ggagtcatgc ctcccaggct 19740 ctgagtccca ggctccgagc attactgagg cagctcctaa gaagagagaa gggaagaaca 19800 tttcctgagg atctttgctg tgccaggttc cagaaggtgc tttggcgcat ctcacgtgag 19860 atacgggctc cttttgcctg ctttctaaga agggtgcggt gtgaggtggc tggctgcgtg 19920 gaagaggcct gggaggagta attccaccag tattgtgtct tagtcttcaa gtggccagtg 19980 cagtaccttg gcctgtggta gatcctgagt aaatgttgac tgaaacgaag atgccatggc 20040 cggtggtgaa gcagggatca gtgcaacaat gctgtgagaa tacagaggca ggggtggctt 20100 ttggagggca cctggatcat tcccagggaa gctgccctct gggcagagtt taaagtatgg 20160 cagagggaag agtgttcttg gcagagggca caggcccggt aggggagtta tgagcaggta 20220 attgtggagt atgggattcc caggggctgg gcatgacgtt gagagcgggg gaggttgagg 20280 ccagactgtg aagggattcc caggccagcc caggactgac ttcagattta catcctattg 20340 gcaacaagga gccagtggag atgtttaatc tctttcggcc tccatcaagt tagcctttca 20400 gtctgtaacc tggcctaagt gttagtccca tgtcatttga accccttgcc tttctctttt 20460 acttaaatta cattcacagt gcgctgtgaa acctaattgg aatagacaaa acgtggtgga 20520 actctgcagc ttatggggcc agttcatgct caccttaatg tgcttataat gtacatttaa 20580 atactgccag ttatttggag ctttcaggtg acttcacttc tctgtgtatt atgtacttcg 20640 cttcctacat ctgcagttaa tttgttaaga gaccttaatg agaaacttca aacagtttaa 20700 atgtcaatta ccaaaaaagt aaggttttca agttccagta atctacccga ttggtcatca 20760 gaatgtagtc ccaggtggat gtaatttaag acatgacatt ccagagcttc agttacaaag 20820 aatttatata tttcgggact aataaactgg ctccagtggt ggctacactt gcaggattgt 20880 ctgcagttat gactcatcta gtaccggcgc tgctcagaac tttctgtcca cggagttcac 20940 actggttttg tgtttgggct ggtgcttttg aatctgaaaa aaagtgcata aaaatatgcc 21000 agaaatgtag taaatattgt gatcatttca ttttttaatc cgacactttt gagaggaaaa 21060 gagtattcat cagtacttta tcatagattt aattaatggg ataatcttta atttctgact 21120 cagacatctg gatttgtttc ttgccacccc ctcctttttt tctgtgttcc tttctcgtct 21180 ttatttttga tgaagataaa atacttaaag aaagcgttga atgtgatgat gagtattgtt 21240 ttaacagaaa gtaaaatcaa aagcatgcag aataaattaa ccttgcattt tctcggcagg 21300 tcagttagtg ggtgttatat ccttagttgt tggtgctaca aagtaaataa tttttggcag 21360 ctggtttagt tttcaccact tctaagccta tgacaaatgg tcttggaaga tctttggtct 21420 taaaaaggaa aattttctgt gtgcgagttt taagttcagt tttgttgggt tttgaagtct 21480 tttttatgta agccacttat gtggcatttt gttttatttg aatttgaaat tttttttaag 21540 ttttaaagct agagtctgcc acattgaact gtttttcaca cttggcattt aaaagttaat 21600 ttgctttttc tgtttttaaa agagactaaa aaactaaggt ttcccctact aagcatttat 21660 tagtcaacca cttttgaaaa ttgaaaaatt agtttgtatg gttttagatt gtttttctcc 21720 caggagaaat aatgttgcta cataatctca gacctgcatt cacgtattta gcctgccata 21780 agtcactgtc aaaatgaaga aaatgctgaa agttagatat acctgcacat gtgaatttca 21840 tgtattttct ggtaatcaac tctgttttaa aggcttttgg gagttgtttt ctttcagaag 21900 cagcccactg gtgctgtatt tggcatgttg tgtgttatta aaacttcata taaatgcaga 21960 ggtactaaaa cgtgaagttt acaaaaccca tcggaacatt tttacttgtg tagttagcac 22020 gatcacttct ccaagtacaa taatctttgt gttgtgagcc tgtagacaaa actcgtgtct 22080 ggcatatctg attggaatgt gaaatttaat attttccact agttatttcc caacatgcaa 22140 agtgaactga tacccattaa atatatatat ttaagtaaaa atagagagga tcagtggcct 22200 aatcagcttt acagctgtga atttaggaag tgaattcaca acatccctct ctccagagag 22260 acgacttgat gacttactct cggtttcttt aagtgatata gtagaccttg tttggattaa 22320 tcagcagcct tgggagttgg agcagtcatt tgcaatattg agtggaaaag ttccttgtgc 22380 ttggaaaagt cagaaggcca ggagtgagag acatggcctc atcctttccc tggtggctcc 22440 tcacctgtga agttgcacca gggtggtaat aaaattgtag gagctcattt tatgtgaaac 22500 cattagcagc ctgggaattc aggactagct gcctttcata ctttaagaca ctggaaggtg 22560 tcatttataa gcatagagag cctgcaggaa ggcagaacag gcttgtaaac tggagcctga 22620 ggctctgggc agcaatcagt gtgtaataga gtttaaagtc ttaggttatc agaatcacaa 22680 atgggccttt aagtgttgtg ggcaaatccc aagaaacatc tgtctataaa aggcaggtac 22740 aatggccagt tatttcctcc tggttattgt gatattgtta ttttctgttt ctgcctttgt 22800 ggatgggagt ggggagagaa agggaggggc ccttgctaca agtgtaagaa taaaattgta 22860 aatgtttgtg ttagttgaaa aaaaattgac tatggtaagt gtcgcagcta atgtagggtg 22920 ttttcacctt gaaacagcga ctgccgccca gttcctgctg cttcgttcgc ggactctgaa 22980 ttccactgct ggggcaggcg tgtgtgacag gcagagagag ccctggggtt gggggaacaa 23040 ggaagtgttt ccagttccca tttggcttat gcattggagg gttccccaat gtggggacag 23100 cgtccaggtt cttggcctgt ggaaatgaca aatggccctg acagggggct atcccagctt 23160 cagtgtttct gttcaccatc ctaagagtgg ttctttatct gaaaccatga agaaaaccag 23220 atgattagag aagaattcaa gaacccattc tgtagacatt gcctcctgac aagtacaaat 23280 gcgtctgttg aaatctcagt gctccaagtc cccatctatc cgccttcccc ctcctccagg 23340 ttttagacag gttacctgat tgcccctggt tggccctcat cccctcccct atctgggcag 23400 cgctctccct gctgtggggt tgggtggtcc tcctgctcct gggtcatatg gtatcgagag 23460 atgctgattc catctgcagc tccttctctg tactgtggac ttcactgctt gtctctttgg 23520 ccactaggaa gcatttattc tgattctcat gggcagcttg agaggcttcc cacagaggga 23580 agggtaggcc tttaatattt ctgtccttca tctcaaagac tgtttcttta aagtggacac 23640 agatgggatt gggctggaga gaggtggccc cagcccagga gatcatgttg tctgggtgaa 23700 accactgcac gctctggtcc ctgggctcct attgctcagg gttccttttt aaagcccact 23760 tgtcgagtct tctttcttta cagaggagat gttgtgctta ccctcttgtg aggatctcac 23820 agtgttctag cgcctctcct tggagatggt atttactggt ttgagggtga cctctgctaa 23880 tggacctgtt cagtcaccag gtacagggcc ttcagttgtg ttgtcgaaga ggctctgctc 23940 acccctgccc caccatatct gagaagtgcc cgaagttagt tggatgtggc ttctctgcct 24000 aggtagcctt gcacccctgg gaggatgggg gcctaagctg gaagtggatt tttctcatct 24060 agcagaagca cattcgatac tggatacaaa gccccatctt ctgtttcaga agcagcttgg 24120 agcatttctt gtttaactgt catgtaagcc ccttaagcaa tgcttttttc agagaggtat 24180 catcctgata aattgtcaaa tgcctctttc aaatccattc cttttaaaaa aaatcctctt 24240 ttctgtttat tctggagtca ctcatcatgc aaataatatc tttgtgagaa gtggtgttcc 24300 tggagttgga gaaggctctt tagtagggct gctggtcagt acagtccctg aaaaacatga 24360 ctatttataa cacaggcacc agagggttca gagacgtgct aaaagtggag aagttggggg 24420 caggggagtg ctggcaagga tgaactttgc ctatttcaca agttttgact aaagtagttc 24480 tgaataagaa aagcgtttga tgaaatctta cctagtataa agacatatta tttttggcct 24540 ctcttttttc tttcttcttt ttgttctttc acctttcccc tgtgacctcc cattccagct 24600 gagccctctt gttcccattt gccctgtatt gttgatctta accccagctc tgccctctct 24660 taaatcctgt tcttattctt ggagaagact acagtctccc gagctctttc tatatgccaa 24720 gcactgtact tttatacatt catattatca tgaggaaata ttcttttgcc tattttacag 24780 atgaagcaag tgagattcag ggaagttaag taatttatcc aaatttacat gcctactaag 24840 ggatggagca ggagccagac ccctgtttct gaagcatgtt tgctgaacca ctacacttta 24900 gccacctact gtggatacct ttggaaagga ggattctttt accgttacca aaaagatatt 24960 aataaaaata agtccaggtg tggtggctca tgcctgtaat cccagcactt tgggaggcag 25020 aggcaggtgg gttacttgag ctcaggagtt cgagaccagc ctgggcaaca tggtgaaatc 25080 ccgtctccac aaaaaataga aaaattagcc acgcatggtg gcgcatgcct gtagtgccag 25140 ctactccaga ggttgaggtg ggaggattgc ttgagcctgg gaggcagaag ttgcagtgac 25200 ctgagatagt gccactgcac tccagcctgg gtggcagagc cagaccctgt ctccaaatat 25260 ttatgtgtgt gtgtgtgtgt gtgtgtgtgt gtgtgtatgt atacacatat ataatttata 25320 tgcaaatata taatatatac atatattaca tacatatatg tgtgtgtata tataatcaaa 25380 tgcccataaa ttgaagattc attaaataca gggatagtca taccatagta atgacgtagc 25440 tgttaaaaag aataaggtag ttcccataaa tggtagaata gcttgattgt actaatcccc 25500 ctgtatttta tgtagatttg taagattcac accaaatttt ttttttttga gttggagtct 25560 cgctcagtcg cccaggctgg agtgcagtgg cgtgatctcg gctcactgca acctccacct 25620 cccgggttca agcgattctt ctgcctcagc ctcctgagta gctgagacta caggcacgca 25680 ccaccacgcc cagctaattt ttgtattttt agtagagacg gggtttcacc atgttgacca 25740 gccaggatga tctcgatctc ttgacctcgt gatccacccg cctcagcctc ccaaagtgct 25800 gggattacag gcgtgagcca ccgcacctgg ccacacacaa agtattttta aaaactattg 25860 taagtcacca gaaagcaagc aaaatcaggc agaaactgga ggagaatcta cctcaaaaga 25920 caaactgcgg tggataaggt ttgcaggttt gtagctttaa cctgaaggta ctcccaaagc 25980 taattaagtg gccaaaagcc gcagccttac tgtattgcga tgttagaggg cagaggtaga 26040 aactggcaga gctggcagag cagtcagaaa attaagaggg aaaccccaga gaggagggag 26100 ctacagaggg cacaaacacc caaatctgca tatgaaattg cacaaatcct tggttggcta 26160 ctaaactatg tgtctgcaaa cctggtgaaa aagtagcagc tttaagcctg aaaaaaacta 26220 agcaaagatc ttggccactg cctaccatag ggaagacaga acttggtatt tgtgttcagc 26280 caagttagct gtctgctaga acaaaaatta gtcttcagag aaatgtgcag aatctggaat 26340 ctctataaca tatcgatcat catgtccagt gtcctatcag aaaccactag aggccgggca 26400 ttgtggctca tgcctgtaat cccagcactt tgggagacca aggcagacgg attgcctgag 26460 gtcagaagtt tgagaccagc ctggccaaca tagtgaaacc ccatctctac taaatataca 26520 aaaaaaatta gccaggtgtg ctggtgggca cctgtagtcc cagctattca agaggctgag 26580 gcaagagaat cccttgaacc tgggaggcgg aggttgcagt gagccgagat tgtgccactg 26640 cactccagcc tggtgacaga gtgagactcc gtctcaaaaa aaacaaaaca aaaacaaaaa 26700 aaccccacta gatagaggta gaaatgggaa aaaagtagat aatagaagcc aaactcaaga 26760 tgatagagat gttacaatta atagacaagg actttaaagc atctaccata aatacattca 26820 aagacttaat aaaaatgtat acacaatgaa tgaacagata gggagtatca gcttagaaat 26880 agtagctatg ggccaggtgc agtgtctcac acctgtaatc ccaacacttt gggggcccag 26940 gtgggtggat cacttgaggc caggaattca tgaccagact ggccaacatg gcaaaaccct 27000 gtctctaact aaaaatacaa aaattagcca ggtgtgggag actgagacag gagaatctct 27060 tgaacgtggg aggcagaggt tgcagtgagc cgagatcata ccagtgcact ccagcctggg 27120 caacagagca agatcctgtc tcaaaaaaaa aaaaaaaaaa aaaaaaagag aagagaagaa 27180 aagaaataag gccaggtgtg gtagctaatg cctgtaatcc cagcactttg agaggcagaa 27240 gtgggcggat cacttgaggt caggagtttg ataccagcct gggcaacatg gcaaaacccc 27300 gtctctacta aaaatacaaa actgggcatg gtggcacgca tctgtaatcc cagctacttg 27360 ggaggctgag gcacaaaaat cgcttgagcc tgggaggtgg aggttgcagt gagccaagat 27420 ggcaccactg tactccagcc tgggtgacag tgcaggactc tgtctcaaaa aaaaaaaaaa 27480 aaatagctat gaaaaagagc tgaaaggtta gtggttgcca gaggttgagg ggaggaggga 27540 atgggaagtg attgtttaat gcatatgggg tttccttttg tgttgatgaa agtgttcttg 27600 agctagtggt gaggcttgta cagcactgtg aattttaaac tttaaaatgg tgaaaattgt 27660 gaattttatg aaaagagagg tgaaaataca tgaactaaat agaaattttt accagtaagc 27720 tcaatagcag acaaagttaa ctgaaaaata gatcaatcgt atgtactcag tttgaggaaa 27780 agaaaaagat tgaagaaaag caaatagagc ctcagagacc tgtgggacag taccaagcag 27840 tctaacatgt atagttggag ttccagaagc aaaaaagaga ttagggcaga aaaaatattt 27900 gaggggataa tgaccagaaa tgttccaaat tcggtgaaat ccattaactc actgatccct 27960 taacaaacac tcagcaagat aaattaaaac acacacatgc acatgagagc cacattgctg 28020 aaatccaaaa ataagaaagt cctgaaagct gcctgagaaa aaaagaaggt gcacagaagg 28080 aacaataata taactaacag ccgactgctt atcagaaaca gtggagagta gaaggtaaac 28140 gtattgaaag acaaaatatc aacccagggt tctacgtcca gcaaaactat ccttcaaaat 28200 tgaagcccaa ataaagacct ttataattaa acaaaaactg agagaatttg ttgcaaagaa 28260 tctgactatg agaaatgcta aaggaatttc tttaggctta agggaaataa ccccagatga 28320 taacttggat ctataaaaag aaatgaacca gaaatgatga agaaaataat cagatagatc 28380 catctgtgtt gatgtaaaca tgtaatagta ataataataa atatttatat agcaattatt 28440 tcaggaagga cacgcaagaa aactttaaca gtgataacct tccccgtgga aaaggggaag 28500 agattgagag cttggagtat gaaaaaggag actaaattat tattttgtgc ttcttttgat 28560 catttgaata ttttttaatg tggatgtatt acttattttt ttaaataaat ttttaaatgt 28620 catgaaatag ctaggaaaaa tagagatact tgatacaaga tgagaaaata atgttctgtt 28680 tctcccttgt aaggaatatg acagaaatcg agacattgta gactgggagt caggattggg 28740 tttctttcct actctgttag caggacactg tgtcacgtga caaaggctgt gaaggaggta 28800 tcagatcgcg ctctctggcc ttgggcacct tctttccatt gctaggtctt cttccccatc 28860 cccagacgtc cctgctcatt cccggagcgg cagctccagg aaggcacatc ttgctctaaa 28920 atggcctcct gaacactcct gttcccacac actgtctggc ttaatcttac tccaaggcag 28980 gcagctgcag agggtgccag ggctggttct gctcctgggt tcccatctcg ggtgatcagg 29040 acaccatcgt gtgctctgtc acccaagcca gcagcctgag agtccgcctt ttaactcacc 29100 ttgttaatga ccccaggtac gtttcattag gtcttcgtaa tgaaatgtac ctgggggtca 29160 ttaacaaggt caattgaccc aaatccttct caaatctgcc gcctttctct gtcatgattt 29220 ttataatctg caccacgccc cccacacccc caaccttttc caggatcaaa ttgagacttc 29280 tccagtgttt gcagagtgag gtcctgtctt tagcccaggc cttcctagcc tggcccctac 29340 ccaggtccaa ccttgttttc cacatgtgag ggtccaccct catctcccag tgaggtcagg 29400 tctggccatt cagcctcccc ttccacatgt tcagccctcc tggctttgcg cagcttattg 29460 ctttttcctg tgttccttcc ttgtcttcac atagcaaatc attctcacct ccagagatgc 29520 tgtgtcctat gtcctagaag ccttacctat tccctagcat gctgaactga gtggtcctgt 29580 cccggcctcc cataactctt gttaatgctc tgtcctactc ttggagagac catgaagact 29640 gggggaagag gacagggttt ggagttggac agatttggtc tcaattctgg tctttccatt 29700 tactggctgt atgagctcag gcaagttgtt taatctcccc agtctcagtt tcctcatctt 29760 tatggtgaca atactactgc ttactttgct gagacagatg gactaaagat aatatatata 29820 aagtgcttgg tgtggttcct attatagctt tattcttaca acactttttt aaacattgtg 29880 ttgattaaac atttacttga ttaaatgttt ttctctccca ttagactata cattctttga 29940 gaccagcagt gcttaatgtt tgtagaattc aacttttaat gagtttgaat tttaacagag 30000 tacatttgct aagttaaaag agtgattata ttaactttaa ttgtggaatt tcacgtaatg 30060 tgaaattcaa agctttatat atattttcag cagagactct taaaattatg ttttcgaaat 30120 aacaatttta tctccccaag caaaatgcca cctgcacctt tacaaacact ttaccgcagt 30180 tatgtgaacc ttcattgctc acccttgctg cagatcatta aatgtatgca taaatagaat 30240 tattaatgtt taccaaggtc ttaaagtcct ggtaagaaaa tattgagtgg tcaatataga 30300 aaggtcacct gttagctcct gatgcttgaa aacagaggtg ggacctggtg agcctgtctt 30360 cagctgatgc agtgccagca catctgggct gggcagggcc tccagtgcct tctgcacagg 30420 ttcacgtggc caactctgct tggacagtgg gatctgctcc ctggcagctg ggacacctgc 30480 tccccactgt tgagccattc ctcttgccag ggctgtttga gtatcagcca ctacattcct 30540 ggccccctcc ttttagagag agatctctga ttttaagagg caaggtttaa agtaagacat 30600 ttcatgtgta gtagcagata ttattaactt tgttgtgcac agtatgcctt ggatcttctt 30660 ttcttgggta gggtacagat aaaatgatgg ttctacgagg ggtaagtagg aaaaattagt 30720 ggttctggat tctctccatg ccttcactcc attatagtca cagtggcaag atggagtatt 30780 agcaagacag gtcctgagtg tggttgcggt ctaatttaaa cttttttttt tagacttact 30840 ctctcgccca ggtcggagtg cagtggtgca gtcttggctc actgcatcac tgcatccccc 30900 agccaggctc aagcaattct catttctcag cttcctgagt agctgggact acagtcatgt 30960 gcaaccatgc ctggctaatt tttttatttt tagtagagac gggatttcgc catgttggcc 31020 aggctggtct tgaacccctg gtctcaagtg atctgcccgc ctcccaaagt gctggggtta 31080 caggcatgag ccactgtgtc caacctaatt taaactttat ctttgtaagt gccagggtaa 31140 tagaggctac ccagtttgcc attgtgctca cccaaagatg aaagtgctaa ggttgagtgg 31200 aagaattccc aattattaag cccctcctct ccctgtgttg aaaattctcc atgaaaaccc 31260 atctctggag gtgtatcaat cagtgttatc actgccctaa gccatttctg tcaaatccag 31320 tctttccagc atattgcata ttccctgtct tgccagtgaa atgtggtaaa gaagaaaaaa 31380 gttgccacag aatgtaattt ttaaaaccat agccgggcac ggtggctcac gcctgtaatc 31440 ctaacacttt gggaggccga ggcgggtgga tcacctgagg tcaggagttc aagagcagcc 31500 tgggcaacat ggtgaaaccc tgtctttact aaaaataaaa aaggccaggt gctgtggcac 31560 gcacctgtaa tcccagctac ttgggaggct gagggaggag aattgcttga acccaggagg 31620 tggaggttgc ggtgagctga gatcgcgcca ctgcattcca gcctgggcta cagagtgtga 31680 cttcatctca aataataata ataaaaccat aaaattccta caaagtgtga atatatattt 31740 atgaatgatg tctgtgtgta tccgtataca tacatccatt catatttctg aaaagctttc 31800 aaggagaatt tttaaacata gcagatgcat taatttgcat acaaagaagc cagttacgga 31860 tcattcttat ctagttatcc aagtcaacag tgcctttttt tttttttttt tttgagacaa 31920 ggtcttgctc tgtcgcctag gctggagtgc aatggcacaa tcgcggttca ctgcattctc 31980 gaccacccag actccagtga gtctcctacc ttagcctcct gagtagctaa gaccaccagc 32040 tacacctggc taatttttat tttttaattt tttgtagaga tgtctcccca tgttgccctg 32100 gctggtctca aatgcctggg ctcaaatggt ccccctgcct cagccttctg aagtgctggg 32160 attacaggaa tgagccactg tgcccagctt aatgatgcta ttaaactaca cctgttaacc 32220 ttctacttgc tttctgtggt tgacaagtaa ttctctttgc atttcttttt actaattcag 32280 atgggcttct cttttcttac tccaaattat tgaaagttat ttatttgtgt aaaatattac 32340 atagacatac acacacacaa tatatgtgtg ccttatgcat tttacaacat catctgaaca 32400 aatatttatt aactacctat tgtgtttcag actctgtgct agacatgcgg gatttcgcag 32460 tgatcagaac agtatctgcc caacagtccc acaaagaaat attaagcaag aataaaatct 32520 gtagccacat acctgtgtac attttttgag agcttactat gctctgggca ctgtgctaac 32580 attttcaaca ttatttcatg tagcactctc aacaactgtg tgagataagt tttatttatt 32640 gttaccattt ttccaaggag gaaaccgaaa cacagaaagg ttaagttact tgcctgaggt 32700 aacttagcat tgatagaatt aggatttgaa cctgggtagt atgactctta ggtccccatg 32760 agctggcaca caggttgcca atccatcagt taaccttccc atcactgggt cagagagcca 32820 aggagcagaa gggggataga acttccccag taccaaacta aggggctgag ctgggatcgc 32880 aaccacaggt tctgttccaa agctggggct ctttcgacaa ggccatgccc gccttgtctc 32940 ttatgtatgc tttttcactt gaggctgaat tttaggtctg agtcaactgc attttgaaaa 33000 aaatcatctg cttgaagacc ctgatgatgt aacaataaag gccattggaa aaccggcaat 33060 ctgtgaatct tcatatagat gaaatatcca ggttagaatt tatcatccta atctggatat 33120 ttttgagagt gaaaggagta ctgttataga tgctggggca tcaggagcca gccaggacgt 33180 ccaggcaagc cggggcttgt ggtcactctg tggacacgca gcatggtcat taatgcccac 33240 acaatgtgtg tattgttatt tgtagattcc attactcttt ggaatataaa cctctaagca 33300 agctaaaata actctactat gctttaatta tgcattgttg gtaaccataa caataaatcc 33360 ttggccaatt ccaatccaag gacataagca tttagagtca tttttaaagg agtgctccga 33420 tggtttagca gtcatgtaaa tgcatttata tgtaacagaa gacaaaaaca ataattaaga 33480 taaacataaa actcatccct tttgcctaca gaggcaactc tatttttaga actacaaatt 33540 tgggctggat gtggtgactc ttacctgtaa taccagcact ttgggagacc gaggtaggag 33600 gattgcttga ggccaggagt ttgaaaccag cctggccaac gcagcgagac catatctata 33660 caaaagaaaa gttaaaaact tagctgggca tggtggcatg tgtctgtagt cccagctact 33720 gaggaggctg aggcaggaca accacttgag cccaggagtt caaggctgca gtgagccatg 33780 attgtaccag tgcactctag cctgggcaac atagcaagac attatcttaa agaaaaattg 33840 tatgcatagc ctgagtacat gatttgaata tatttaggaa atagataatg ggataaaata 33900 ttcaaaagtg aaattatgca ggaaaattcc aggcatgtga ttgtcatata catagttgaa 33960 catttctatt ctctatgtag tttagacttt aattaaacag aataatctga ctttaatctc 34020 tcttgatact ataaaagtaa cttgaatttg ttcatttttt gttttttaat catgaaaact 34080 aatgcccaaa gtacctgtct aactcaaaat aattgtttct tttttcacac aaagccaatt 34140 gaatagattg gacaattgca tacttaagat ttaatatatt tgctcatcat attatgggtt 34200 ttaaaaaatc atttatcttg gagctaagta catttcacta tggtttttta tgttcattgt 34260 cgtaaaatat tatctttaat gtttcactag gttcactaat gttaggctga gggtgtttat 34320 tgttgtatca gatatccttt tgtgttttat ttaaatctat atttactagt tttaaatagt 34380 ttgccttatt gctaaggcta gtggaaaata gttaaagtgt gagaatgtgg tttttccctg 34440 tagtgttctt ttgagtagtt gacagctgtg aaaacattta gcaggcttcc ctccttttca 34500 gcgttggtta agctctgctt ctaaaggagt attcctagca gagcttgcca cagtatatcc 34560 aaaacattgc tgtattacag acgcaacatg gtttaaaagg aaaaattgag tgtgggtttc 34620 aagttgacac atgataaaag tagccctgaa gtgttcaatt agaaactgaa ggcctggatc 34680 tgataacttc atgggcagtg cccctgctct tttgtcttac gaccaatagg attttgactg 34740 ctcaggaaat ttgtatgcat gtacccagat atagacctag gcacctaaat gcacacgtgg 34800 atatatacga atatatggtg gacagtgcag atccaagcta ctcctgctaa cacatttctg 34860 gaaaacattc cctttatggg aggacttaac aaaaaaatta gtagctagtt ttactttggt 34920 ttacatatat tgtttttcta atatagaatt ctcattagtt ggttttatga atcatatcac 34980 caaatgaaaa tttgaaaagt atgtaacagt tttctattga gcgttctctg aatattcttg 35040 ccttcagtcc tgctgggagc cttttctcag atcaccagtg caagcctaca gtcatacatt 35100 gtttgtagtt gatacaacct caatgatata agttttttga tgattttaaa atatgagtaa 35160 ttaatcattt ataacctata ggttaaaatg aattataagt ggatgaaggt gggaacccaa 35220 atgaatcaaa gctatttaag tttggtattg acattgtgca tcttcccatt atttattata 35280 ccaaaaaaat cactttattt cttaaaaata gtacaacacg gccaggtgca gtggctcacg 35340 cctgtaatcc cagcactttg ggaggccgag gtgggtggat cacgaggtca ggagatcaag 35400 accatcctgg ctaacacagt gaaaccccgt ctctactaga agtacagaaa attagccggg 35460 cacggtggca ggcacctgta atctcagcac ttttgggaag ccaaggtggg cggatcatga 35520 ggtcaggaga tcaagaccat cctggctagc acggtgaaac cccatctcta ctaaaaatac 35580 aaaaaaaaaa aaaattagcc aggcatggca gcgtgcacct gtagtcccag ctacttggga 35640 ggctgaggca ggagaatggc gtgaacccgg gaggtggagc ttgcagtgag ctgagatcgc 35700 accactgcac tccagcctgg gtgacagagc gagactccat ctttaaaaaa aaaatagtcc 35760 aacacaagaa ggaaagaagg tacagaaatg gaaagttaag aatgaatcag tggagtaaaa 35820 catttctgag attggtgcat tttccttttg gaaatgtcat tcaaaccata tgaaattaaa 35880 tttggaaata atgttctgca gtctcttgaa tgggatttaa aatatgacaa tgcagaaaac 35940 acatatgggg atgaaaaccc ataggacatg tctcaaggag gacagacacc ctggggaaga 36000 acacttgtga gggtaccagg ctctcagaca caaggaaaga ggaatctgag ggattgctgg 36060 gaaggattct catcttatga ccccagctgt gggtagattt ggctggggag cccattctca 36120 ttgcaggggg cggtggcctc agccctgtgc atgctgactc ttcagtgctg tgctctggct 36180 gaggcgtgcc tctagtgagg gtgaccctgg gcaccgagca tattcagtca ccatcagcca 36240 aagctggttg taggagggct ggcggtggtc ttgggaatgt tgcttgaatc catcttgggg 36300 tgaaaatcag agtattggct catttctatt ttttatgatt attgttatta ttattattat 36360 tattgagaca ggatcttgcc ctgttgccca ggctggagtg cagtggcacg atcacagctc 36420 actgcaggtc acagctccca ggctcaagca atcctcccac ctcagcttcc cgagtagcta 36480 agacttcagg tgtgtgccac ctggcctggc tcatttttta atttattttt gtagagatga 36540 ggtctcccca tgttgtccag gctggtctca aactcctggg ttcaggtgat ccttctgcct 36600 cattcttccc aagtgctggg gttacaggca tgagccacca tgcccagcct ctccttcctg 36660 cctgcctgct tccctccctc cctcccttcc tccgttgctc ttttattttc tttccttttt 36720 tttcctgttg ctcaggctgg agtgcagtag tgcaatcttg gctcactgca gccttaacct 36780 cccaggctca aaccatcctc ccacctcagc ctcccaacta gctacagcta caggcataca 36840 ccaccacgcc tggctaattt tttatttttt gtagagccaa ggtcttacta tgttgcgcag 36900 gctgctctca tttctaatac actgagctca actgcttgct gggtgaggcc tgcatgagga 36960 ctttactcat gggctcatag aagccctttt aagctgctta gtgtccttag agtctccaga 37020 ggcatcccta acccagaatc ttttgactgt cctctggaga gaaaggcagt aggtctgtac 37080 caagaccaag gggcttgaag gcttggacgc tctgcttcca cctgcctctg gagtggccag 37140 aagtaatgcc tgttctcatg accagccagt ttgcctcact gctccggtgc caaaggccaa 37200 gttttgattg gaatgatgtc tgtatattct gaataaccag gaattttgtt tttctgattt 37260 acagatcttc aggcttttca tcagcatgat ttgccatctc tgtctttgtc atctagggtc 37320 tgtaattatc ctcaggtttt ctgccaatac ctgcattttc aaccagttag aaaaagaaga 37380 gctaaaacag gtagaagcct gaaaccaagg ggcatatgca tttctgaaac attttcaaga 37440 aattgtctca attttatatt tctgtttata attataattt caatgtccag tggaggaagt 37500 tgtgagactc aatgtcagta gctaccactt actattctgt gcgcctcggt tcagattgtt 37560 tggggcagtg gtgttttatg ttgtgggtcc aaacccatga gtcatctggg aagttaattt 37620 attaggtcac aatgagcgtt ttaaaaaatg aaccataggc ccggcgcagt ggctcacgcc 37680 tgtaatccca gcactttggg aggctgaggc aggtggagca tgaggtcagg agttgcagac 37740 cagcctgacc aacatggtga aaccccgtct ccactaaaaa tacaaaaatt aactgggagt 37800 ggtggcggcg cctgtaatcc caacttttcg ggaggctgag gcaggagaat cgcttgaacc 37860 caggaggcgg aggttgcagt gaatccagac tgcgccattg cactccagcc tgggcgacag 37920 aacaagactc tgtctcaaaa aaaaaaaaaa aaaaaaaaga actgtaacat aataggaaat 37980 attcaattct gagcccatca cacattttgt cttatgaaac ttttggtttt ttatatgtgg 38040 tgtatgtatg tatatgtggt gtatgtatgt atatgtggtg tatgtatgta tatgtggtgt 38100 atgtatgtac atgtgtatgt atgtatatgt ggtgtatgtg tatatgtggt gtatgtatat 38160 gtggtgtatg tatgtatatg tggtgtatgt atgtatatat ggtgtatgta tgcatgtgca 38220 agctctcact ataaatacac ttcttcctgt gggttgcagt aaaaaaaaat ttgaaaactg 38280 ttaccttaag actatttatt ttaaaaattt taataggtac atagtgtata tatttatggg 38340 gtacatgaaa tgttttgata taggtataca atgtgtaata atcacatcaa ggtaaatagg 38400 gtatctctga cctcaagcat ttgtcatttc tttgtgtttc aaacattcca gttatactct 38460 tgtagttatt tttaaatata taataaatta ttgttgactg tagttatcct gttgtactat 38520 caaatactag aacttacttc tttctatctc actggatttt tgtactcatt aaccatcccc 38580 agtttccttc ctctacccca ctacccttcc cagcccctga taaccaatat tctagtctct 38640 gtccccatga tttcaattgt tttaactttc agctcccaca agtgagtgag aacagttgaa 38700 gtttgtcttt ctgtgcctga cttatttcac ttaacataat gtcctccagt tccatccata 38760 ttgttgcaaa tggcaggatc tcattctctt ttatgactga atagtacttc attgtgtata 38820 tgtaccacaa tttcttgatc catttagcta ccgatggccc cttaggttgc tcccaaatct 38880 ttgctattgt gaatactgct gcaataaaca tgggagtgca gatatctctt caatacactg 38940 ccttcctttc ttttgggtat atacctagca ttgggattgc tgggtcatat ggtagttcta 39000 gttttagttt tttgaggaac ctctatgctg ttctccatag cggttgtact aaattacatt 39060 cccattaaca gtgtacgatg gtttcctttt ttccatatcc tcgctagcat ttgttattgc 39120 ctatctttta gataaaagtc attttaggcc gggtgcagtg gctcacgcct gtaatcccag 39180 cactttggga ggctgatgcg ggtggatcac gaggtcagga gatcgagacc atcctggcca 39240 acatggtgaa accccgtctc tactaaaaaa atacaaaaac ttagctgggc gtggtggcgg 39300 gtgcctgtag tcccagctac ttgggaggct gaggcaggag aatggtgtga acacaggagg 39360 cagagcttgc agtgagctga gattgcacca ctgcactcca gcctgggcga cagagcaaga 39420 ctctgtctca aaaaaaaaaa aaaaaaaagt cattttaatg gggtgtgata tcttaccgta 39480 gttttgattt gcatttctgt ggtgatcagt gatgttgagc accttttcat atgcctgttt 39540 gccatttgta tgtcttcttc tgagaaatat ctgttcagat cttttgccca gtttttaaat 39600 tagattatta aatttttttt ttcctattga gttgtttgag cttcttatat atcctggtta 39660 ttaatccttt ctcagatgga tggtttgcaa atatttttcc ccattctgtg ggctgtctct 39720 tcactttgtt gattgttttc ctttgctgtg cagaagcttt ttaacttgac atgattccat 39780 ttgtctattt ttgcttcggt cgcctgtgct tttggggcct tagggcaatt tctgatccag 39840 ggagagggct ttctttaagg ggtgtggggc atgaataagc caccagcaat gtcagggtat 39900 cttctttcct gtggctgaga aattccctaa tttaaactta ggattctgtt tgccatgaac 39960 atgctattaa aatagtggca ccctgggaca ctgtggggtt cagtgggctt ttgtgagcta 40020 tcctgaggtc ctaaccatca tttgtgacat tttttccatg gggaaaaatt cattttcagt 40080 tccaaagaag caacttattg gtgaattatt ttgagcagga tcctgtcata atcaggcact 40140 gcttttatat tttttctgta ttcagtagta aatctacttg taccttaagc agtcatcgca 40200 ctcctttagc cccttttaat ttctaatgag gagtggtgtg ttataggagt ttggggtggc 40260 ctgggggaag aagggttgct gaaggatgga gctcctgaaa gggagggtta atgaggatgt 40320 gtgtccaaag ggtgaatgtc tgtgctcctc accagggaga agggcatctt gcatttacaa 40380 tgatttataa ttcacctggg tcaggttcct ctgactatag gagccaattg gttacagaaa 40440 tctttttttt tttttttttt tttgagatgg agtctcactc tggcaccccg gctggagtgc 40500 agtggcgtga tctcggctca ctgcaacctc tgcctcttgg gttcaagcaa ttctctgcct 40560 cagcctcctg aatagctggg attgcaggtg cccgctacca cacctggcta attttttttt 40620 tttttttttg tatttttagt agagacaggg tttcaccatc ttggccaggt tggtattaaa 40680 ctcctgacct cgtgatccac ccaccttggc ctcccaaagt gctgggacta caggcgtgag 40740 ccaccacgcc tggctggtta cagaaatctt aatataagga gctcgttaca aaggcaagca 40800 taccctagat ctgcctgcta gccctgcgat agctacttct cagtaccttc tgtgccagac 40860 actcttctag gcccagggat acagcaggga gagaggtggg cagggcccct tcccctctgg 40920 agaggctgct gctgggccct ccgcacgctc tggcctccca tgctttggga atgcttgtca 40980 ctgccaagct gtgcagtgca tcaccatcca tggtgctcat gggcctgagg accactctgc 41040 ccacacctaa ggggggctgg gtggccagtg tttgaaaggc ttataagaaa gatcacaaga 41100 agtttcttct tgagaaatgc tacagtcttt aaaaacaaaa caaacaaaaa actacttaga 41160 attttgatag ccccagctca agaaaacaat aggtaggaca caagcttgtt cataggcagc 41220 agagaggtcc aaagcaatgt gcctcaaatc aagacgtgtg gctctgaaaa accttcttag 41280 ggaaggctcc cgccccacct agagcttccc aattccatag tatctaaggc cttgcaaaat 41340 ctacatctgt cacacgcccc cccggccccg ccccccatca caactccata gtgggaagaa 41400 cttatttcag tgcctatttt tcttgaggtt tataaaaaca aaatgtgtga agggaatgta 41460 tgctgattct cttgggacta attaaacaaa cagattcaga gaaagaaagc agagaagatt 41520 taggacagtt aaaatgtaaa aaatgtaatt ttggggataa cagccgtcaa tttttccact 41580 cgagtgtttt tccaaagggc agagggcaag aagcatctta agtcctctcg aagctgagac 41640 acatttcaac tggagatatt agaagcaaat ttggtgccca agacaggtgc cagattttaa 41700 ttacagttgg catttctgag catgcttttg gcagaggtgg ccatcttgtt ggaaaagcca 41760 tagattttga cactagcagt atgggtgccc agttgagaac gattgcaaat aatttccctc 41820 ctattttcat cttgttggtt gtgagagaaa acttcagtgg ctaatattta aacaagatat 41880 tctctgttca gaggaaacag ttcattggaa ttgtcttggt ggcttggtgt gttggctctg 41940 ggggtaataa tttctatctt aaagtcttta aaaccagtta aaacaataaa ataggatatt 42000 tcattatgag aaatgaagtt ggcatgcacc aggttttcca ttaagttcca ggtcacagac 42060 aaataaagaa agtatgttcg ggggggaaaa atccttttta aaaataatta gggagctgtc 42120 tgttttgttc accagatgga aaatccgtag ttgtgggtgg tctgtgttgg agagggcatc 42180 tcacaattgg caggactatg cctttaactt ttcaagtcct cggacaaaaa tctcaacgcc 42240 atggactatt cagaaggctc cgaatgttca tcagtccttc caggtctgct tttctgaatt 42300 ttaccagttt tctaacaaga gtgtgtaagc aaaatgatta tggaatgccg aaataaatag 42360 tccattgttc gttgaattct gaaacagcat tcctgctagc cctggttttt tgtgactttt 42420 cttgctgtca ataccttatg atgataatct gattagtgga gctgcctgcg ttactattta 42480 aaggcccctt tttcttacat ttctgtgttc cagagtagat agggcagcca gatgtgctaa 42540 cagcataaga aatcatcata agcttgttat ttattgaaga tggatattgc actgttatca 42600 gtgtttaggg tcttttctac acttgctttg attctggtca aattaattca ataagaaaat 42660 gtacttttct tactcctttc ttgaactgat aatagaatgt tagctaccta gtgtcactag 42720 tatttttttt atctacacat caaggtatca tttttttcta gctcagtctt atgttttaca 42780 tggctttaca tctgcaagtt ggactttgaa atgaatattt tatgtttgaa cataaggata 42840 tatatatttt tatatttcat tcatacattt aacccatccc caaaattttc ttaaaaaact 42900 taataattac aggagatgta aattaataaa atcatctagg atgctaaatg cataaacttt 42960 caattgagtg aaaaaaagcc ctggaacgta aatcattttt ctcggacagc caatgtgttt 43020 ggctttggat gtacatcaga ttctgcctgt gcatagtaaa aatggcaatg atttattagt 43080 tccatctccc cccagcacag atgctgcaca gtctgtccct tttctgggca ctaaacagtg 43140 ggttttaaaa aacataattt cactcaagtt ttccgcttgc attctgtgtt gtactattaa 43200 tagcaaccct ttgttattca tgccagctcg cttctagcat aagacaatga tgtggggaaa 43260 cggttttaac taaaatacta ctaattggca cccatttttc atatactggt gcaggtgcag 43320 ttctgtgagg aatagaagca cctctaaaaa ttatgtcatg aagatagaaa agctaaacag 43380 ttacacagtt aagtaggtgt acctttgcaa tgtcattgtt tctttgaaaa atcttactta 43440 tttgccgata agttgaaggg tggggaaaat ttggaatatt gatggaggac ttatgtgtta 43500 aatgttctat gagtccacca ggcgctgtgg ctcacgcctg taatcccagc actttgggag 43560 gccaaatcac gcagactgct tgagccggga gcatgagacc aacctgggca acagagcgaa 43620 accccatctc tacaaatgat acaaaaatta gccacatgta gtggtgggca cctgtagtcc 43680 cagctactca ggaggctgag atgggaggat cacttgagcc cagaagttgg agtctgcagt 43740 aaacagtgat catgtgccac tgcactccag cctgggcaac agagcaacac tttgtctcaa 43800 aagaaaaaaa aaaaagttat atgatgcttc atgaaaaaaa aagaaagttt tcagcctgag 43860 caatatagca agacctcatc cctacaaaaa attttttaaa aatcagactg gtaggccaag 43920 cgcagtggct cacacctgta atcccagcac tttgggaggc cgaggcgggc ggatcacgag 43980 gtcaggagat agagaccatc atggctaaca cggtgaaacc ccatctctac taaaaataca 44040 aaaaattagc tgggcgtggt ggcgggcgcc tatagtccca gctactcggg aggctgaggc 44100 aggagaatgg cgtgaaccca ggaggtggag cttgcagtga gcagagattg cgccactgca 44160 ctccagcctg ggcgacagag ccagactccg tctcaaaaaa aaaatcagag tggtatggtg 44220 gcgcacacct gtagtcccag ctactgggaa ggctaaggca ggaggattgc ttgagcccag 44280 gagtttaagg ctacggtgaa ctatggttgt cccaccgtac tccagcctgg gtgacagaat 44340 gagaccctgt ctcaaaaaaa gaagttttca agaggggaag aaataagaag agtgttagaa 44400 acctcagttg cccatctact ttcctctcct tgcccagggt gacagaaact gttgccaaat 44460 tctcactggc agcaacttga gttttgattt ggctcaggta catgtgctct tctagagagt 44520 aaggtcagca cagaggctgc tggagggtgc tggaggctgc ctccatggac tctagcacca 44580 cctttcctcg tcctgtagct gaaatccttg gagtcattct tgcctccact agacccttgg 44640 attctgtgca tctccacatg gctcccagcc attgtggctc tttttttctg ggactctcct 44700 ctctcctgtc catcttccag aagtagcttt ctgaacacag acgtcattgc gctcctctcc 44760 acaagcagca gtcactctca acactgagga atgaagacct tacagtgttc tttacaccct 44820 aacccaagat taccttccca gaatcatctt cctaccccat gtctctgacc ttccaatcac 44880 attaaaattc tcagggtggt gagatactcc agctcctttc tgtctctgcc atggctcatg 44940 ctgctgcttc tccctacaga gccctcctct catcttcctt gagatcttgc tgaccaaata 45000 tcttctcttc tgatgactta gcagtcaccc acactgccgt gggccagcag acacccttcc 45060 tctgccttcc agtagctttg cccaatgtga tctctgctct ttgtaccctg tgctgtctcc 45120 catgttagat ccaaccacct aggtcatagc gctactgctg gtacctgatt gcaggcccag 45180 catctgtctt ggtgccaagc acatgacaag aactgaataa ataggccagg tgaggtggct 45240 cacgcctgta atcccagcac ttggggaagc caaggcgagt ggcctgacgt caggagttct 45300 agactagact ggccaacatg gctaaacccc atctctgcta aaaatacaaa aattagctgg 45360 gcgtagtggc gcatgcctgt aatcccagct acttgggagg ctgaggtggg agaatcgctt 45420 gaacccagga gacggaggtt gtagtgagcc aagatcacac cactgcactc cagcctgggt 45480 gacacagcga gaccccgtct caaaaaagaa ttgaataaat attttttgag tgaaatggaa 45540 ttctgggttg tggctttcca tcagttaaga ttcttggttg tggccaggtg cagtggctca 45600 cgcctgtaat cccaacactt tgggagggag aggtgggtgg atcatgaggt caggagtttg 45660 agaccagcct ggccaacatg gtgaaacccc gtctctacta aaaatacaaa aaaattagcc 45720 aggcctggtg gcacgtgcct gtaatcccag ctacttggga ggctgaggca ggagaattgc 45780 ttgaactcgg gaggcagagg ttgcagtgag ccgagatcat gccattgcac tccagcctgg 45840 gcgacaaagc aagactccat cttgggggga aaaaaagatt cttggttgta agcaacagac 45900 accacatctg gctttggcaa gagggggttt tcctggaagg atatggacac attcacaccg 45960 tcggtggaaa gcaactgtag gcatgccgac atgaatcctt ctccattgtg tccctgctca 46020 gccacgagaa cagtgtgctg ccagggtgct cagtctgtaa ctctgctcag gatgcaggct 46080 ccagggaggg agtgtccaac tgggctaata gggcccaccc tttggctctg ggagagctgg 46140 gctccttgat gataatccca gcacactgtc agctgtgggt aggatgaggc aagttcctca 46200 gggggtgaag tgtgttttgg gatagtcaac agccagtgac tgttcaccac aggactaaac 46260 cttccatttc cagtgctcca gtgccccaac tggcctgtct ggtgtgattt gccaagtgtt 46320 ctgagcaagc agggaagttg tccattaaaa tacagatatt ggccagacat ggctcacacc 46380 tgtaatccca gcactttggg aggctgaagc gggtggatca cttgcactca ggagtttgag 46440 accagcctgg gcaatatagt gagaccctat ctcaattaaa aaaataaaaa gcagatatcc 46500 tgggaaggga taacactata gcccctgcta gccagcattg atttgccaaa agtaggacct 46560 gtgggtgcag gatccagagt agccatggat ggatgaggtg cgaaagggtc ccgaatgttc 46620 cagcaatgct acccaaatgg caagtggtgt cgtggcctct ttcacctcca tactcaggga 46680 gaagccactc agaggcctcc acataacagg caggctctcg cctgggtgtc ggaggtgagg 46740 atgctactga agcttattgc ttcttaagaa tcaatcaaat caaaacaatg gatgcccttc 46800 tcccaagtgg aagggctgtg ctggccacct tgtatgactg acacaaagtt gggaagagtt 46860 gcagtcatga gctggggaga cacaccctaa aagcagatga gctggtggcg gtaaataaca 46920 ctcccatgac gacaagtggg ctttgcacgt gtgtggtagc agggcatggc cctgggggag 46980 gtggggctac ctgaggaaaa tcacaggagg caggaatgta tactgtttgt tgggaaaaga 47040 caagccaatc tgaagggcaa gggtttgtag aggggagtgg tggagagtga ggttggaagg 47100 gtgtttgggt ccagttgtag acagccttga attctaggca aagacttcag atgttgtttt 47160 ctaagcacta ggagcacctg tggatgtttc agaatgggag tatcatgatg gatgtactat 47220 tttttaaaga gcaggaataa gcagcaggcc actgctaagg aatctgtgtc atgaggctgt 47280 tagcctgggg acaaggagga ccggccaaaa aaaaaaaagt cctgtatata agggggagca 47340 cccagcacac ttaggttcca gacctccatt cctagcaact cacctgtaac tcctggcagg 47400 ggtctctgcc tccctctact catccaaaga tcatggtgct tgttcaccag ccttatgatg 47460 atccaaagaa atagtgatct ttcatgttta aataaaccta cttaattacg tgcatctgtt 47520 tggaaattca gacacaccac atgagaagct actgggactt ttttctcctt ttcttggctt 47580 ctcatttgtt ctctagcttt ttcttttttt ttcatcctgg ccagttatta accttctcct 47640 ccacttttga gtctcataat tgtccagatc tcccaggacg ctgacagtgt ggttttggtt 47700 cacttgttcc ttctcctgct caaatttcaa ttgattcaag ggtgatatgc tgggtatgat 47760 gggctggaca tgcccatttt cattcaactc atccataact aggatataag tgaggataca 47820 gatttgggtg ttatggccaa aagatcttca aatacaatga ctttatcaag gataatttct 47880 tcccccctca cttgaaacat ggttaggtgg tgcagggctg ataacgatgg ctcagtgagg 47940 tctcaggctc ctttagctat ggttctgcca acctcagcac atggcacaca tcttccccaa 48000 ggcggctgct tggtttgctc ccaccacgtg gggtaggggg acacatgcct tcctttatgg 48060 ggacactata tttctgctca ccctgaccac atcccatcaa tcagaacttt gacccatgaa 48120 tacactcaga tgcaggagag gctgggaaat gttttcctta gctgggcatc catggacctc 48180 tccctgggtc catcctagag agtggagtag cagcatttgc accccagacc tgaggggtag 48240 ctgaggctgg gctggcagtg gggagtgagg ccaggagctt ggatgtgcag gctggcatgt 48300 cccacacata tggggcaaag aggaggggct ggctggggct cgtgtcctcc tccgtaccct 48360 catcccaagc cccagtgcgg tagggtgggc tgctccaacc caaatcttct tctcccaagt 48420 cttctctttc ccagcatatt atgctgcttc catttcacca tagtttcact cactatcaag 48480 gtctccaaag caatcccatc atctacatat tacttgattg ttgtgtacag ggtattgggt 48540 gaaaatgaag gtgggcagag cacatagcct ccaacctcaa agccagtaat gtgccagatg 48600 aaaggtaagt cacagtcttt agattcagta gcattttaac aaaactaaaa tgtcaggccg 48660 gatgccgtgg ctcacgcctg taatcccaac actctgggag gctgaggcgg gctgatcacg 48720 aggtcaggag atctagacca tcctggctaa cacggtgaaa ccctgtctct actaaaaata 48780 caaaaaatta gctgggcatg gtggcgggcg cctgtagtcc cagctactag ggaggctgag 48840 gcaggagaat tgcttgaacc cgggaggcag aggttgcagt gagccgagat cgcgctccga 48900 agtccattct ttctgtgcag tggctgatct atcagaagaa gaaccccctt ccccaccagg 48960 cctaagaacc catgggagtg atggcccagc actatggtgt tgcatttctt tctttttttt 49020 ttttttagac ggagtcttgc tgtgtcatcc agggtggagt gcagtggcgt gatctcggct 49080 cactgcaatc tctgcttcct aggttcaagt gattctcctg cctcaacctc ccaagtagct 49140 gggattacag gcacctgcca tcatgcccgg ctaatttttg tatttttagt agagacgggg 49200 ttttaccatg ttggccaggc tggtcttgaa ctcctgacct cagatgatct gtctgcctcg 49260 gcctcccaaa gtgctgggat tataggcgtg agccactgcg cctggcctgg tgttgcattt 49320 cgttactggc aagatgatgt atgctctttc acgtgcccac atgcaaaggt gtgactcatg 49380 gaatgaagac agctcagcaa cctctagttg ctgggacaga aatgcaagtc agtgggctct 49440 ggcctttctc ccaggctgtg ttgccacctt ggtggctgga ggggcgctac tagggggtgt 49500 gcttggcaga gcctggggtg gcgtcctctt tcatcccact aaataacaca ttggtggctt 49560 gatctgccat gaagctgaca atcagagcaa gtatttgaag cctgggaagc tgtgtgggcc 49620 ttgcttgtgg gacctggtgt cagctgatga cgtggccctg tctgggtgcc cgtgagtcag 49680 atggcaggga tggcctgaca tcatgaacac tagctccacc tacgtcacat tggacttgac 49740 tctttacaga gcacctagga agagatattg atgagtgaac cattgcccag tcatcgagtt 49800 aattatttcc ccccagaaag gttaacatac tgaggacaga gagggcatgt gtaggcggca 49860 gggcgcactt ttcatttagt ctggttcgca ggtgcggtca agacgattcc ttattgtctt 49920 ggagccagcc cttttaagcc ttcctgcaca gctctgtgac agtctcgcgg ggagacctgt 49980 gaggccactt tccttttttc cagacccacc cccacctttg agattatcac tcttcctgct 50040 ttgttttctg aggctttttg gctttttagt ttatttgtaa ttagagcaga aaaggtacag 50100 taatcggata gaagggttgg gagtgataga atgagccagg atgcggtgga gaaatggggt 50160 ggagaacccc cagaccttag ggtggcgtgt ttgtcaggga gtagaccagg gtgcagttct 50220 aggcagacca ctagatggca ctcacacatt ggtgttcagt cgggtccacg gcactttcca 50280 ctttgggctt ctgtaaaatc tccccatgaa ctagccaaag ctttgtatct gtcatcccgc 50340 catttgtccc tctaacctct cttgatcgtc tacagatagg tatatatata tgttcctctc 50400 tagttcattt ttctcttaac atttagtgac cttaaaaacc tggcagaaat accttcaaag 50460 cctcccacct tgttagctgc attgccgcat ttttactgtt ctcctaagcc aatgtttaca 50520 tggcagtaaa tccatgttta gagtaggtaa tagagaaacc tgtttctctc tcagtcactc 50580 tgagggtatg tttgataaag aaatggaaat tgagaggatg agttattaaa aggattaata 50640 ggtaacaaat ttttttaaaa tttccattca aaattatggg ttggtaaatt gtaagatact 50700 taaaattaat gagttgtttt atcaaatcat tttctgttgt tagagaattt tcagcaagct 50760 gagattcaaa tgcaaaatgt cttattgcat actgctggct ctaggaagga ggagggacag 50820 acaggaaatc atggttgatg ttatctttac caaggtgcat gtggtgtgaa agcaaaaccc 50880 catcttaaat tcatcatccg ttctgatgtt gcacagaaat gaaaattaat ttctatatgt 50940 caactaaaat ggattctgct cctgcctggt tcaattctgt cttagctgcg tggacatctt 51000 ggggagctgc tctgatggta catgcagacg tgcttcatct gtgcacttct tagctgagat 51060 aacagtgctc cgagccccac tgttaaggtt aacctgtata ctgcagaagg acaacagatg 51120 gaaattctgg tttgcagcca ctgcagaaaa ataaaaacat gttccaaagg gaaaaggatc 51180 ttgtatttct gcgtttgaac ctttgatccg cattcacatc tgaagggagg gctaaacctt 51240 ttggtggaga cacatggctt tgcatctgtg aaaacacagc tgtatagagc aaaacaaaac 51300 tagtggaaaa tacaatggtt ttgctgtgtc aggctcaccg ctaatgcttg aattctatat 51360 aaatattgtc ttttgatagt tctttcaaaa atctttcttg actttccata taattgtcca 51420 ataatgttat tcttttaaat tcagatttgg ggctttttag gattaaggca caaatgtctc 51480 ttttctttta aaaaggcagt aaaataaaca gattgtagtt agatcataat aacatctaaa 51540 ttttgaccta attagagggg gagatgggga aaaaaactct ttaaaagaag attaaggtaa 51600 agttctaact ttatccttga ttctgaattt tttttctttt ttggaaatat tgcatacatt 51660 ttatactgca agttacaatg tgaagggcct ttgaagcact ctaaagagac ttagctgctt 51720 tgttttgagc aattaaggtt tgttattgag tgaattaagc agctctgctg tggctcatct 51780 gtaaatagtg gtcttcagcg agtttcttga tccgcttttc ccaggaacag aagccaagtc 51840 ggcttcctta ggagctgctc gccctgagtc tccatgtttc ctcgcagtcc ggggcagaac 51900 ccaagcccgt gccttcctcg ccctgccttc ggagtttcct gctattgacc tggcggggcg 51960 cgccagccct ccctgcccgc tggtgccgcg gtccctctcg gctgcagcag tggggcacag 52020 ggacgtcatg gacaaaagac gaggatgcca gttcgatgtg cgagcagaag gccgcctgcg 52080 tgcgctctgc agagcaaccg gcccggtttc ataaggggcc gccggcaggg gactgccatg 52140 gcgccccctc ctaccctttt tggcaccagc agcttcatcc gcaggcccac tcggggtgaa 52200 tagtgtggga gctctcaaga gaaagaattt taggtttgtc gatagtaatc accaccttca 52260 gcgctcctcc cactgctgga gagaccgcgg actgggtgac aagtcttcca ggctcccaga 52320 aagtttctgc tgcaaagcgc agggtccgcc tcccacttcc aggagggacc aggagggaac 52380 catcgcgaaa ccccgaggct gccggggact ctgactgagg cctttcctcc tgtgtccctc 52440 tcccccacgc cggcctcccc tcctttcaac tctctgcgct ttgaaaccgc ggagttgggg 52500 tagctaggcc ctccagcccg gcgacaggcc tcggccacag gcagcggggc ggggtgtgga 52560 caggaacaag gaggtggggt ggggaggaag cctcgggcag agcaggttct ctgcggagtt 52620 tcggcagccg ggtttatcca ttttgattaa agaaaagtaa aaaaaatccc ccaaaaccaa 52680 acaacaaaaa ccctctccca acccccaacc cgcctccaca gctgcatttt gttcctggga 52740 ctgttggtgt caccagagcc tcttttttta tgcaatccta gactccattg caaaggactt 52800 gtaaagccta ttaatttttc aggcaaaaca gatcaagcct gcctttgatg ctgctgtttc 52860 ctaatttagt attcaaaggt aaagaatcct actaccgtct cttcactttt tacataatta 52920 aaagagattt ttcccccagg ggcaaagaac tagttgctta gtattttttg aagtgaaagg 52980 tctaacttta tatcacatct gtttttatgc tctttcctaa acataaccaa tatttactct 53040 ttgctggtac ttagttgcat gctattcacc cttgcatttt aatttctgac agagagggga 53100 ttagtattcc tcttctaaat catcctctaa gctatgtgtg tgtgtgtgta tatatatata 53160 tgtatatata tgcgtgtgtg tgtgtatttc tcctctaaca aactgagagt gcaatttaaa 53220 aaactgtaga atcagtgatt gccctaactt gtgcatgact cttgatttca cacaggagca 53280 ttcaaaagtt ccgttaagtg ggctttcaca ggtttccatc tgctgtgttt aatagcaaat 53340 tgcgaccctt caaaccactt caaggccttt tgtgttctta tctgtgcatt tcaatacttg 53400 ctggggaagt gccttcagtt tcactacata tgcaaaaagc caggcttgaa ttttttgaca 53460 cccccttttc atttgttggt ggagtcctgt tttctattgt ttgcttgttg atgttggcaa 53520 aagtcattta tttaatgatg ccaggaatac tatgccctat tctttattgg caggaaatcc 53580 taaaacatcc gggagtagtt taaaaattaa tgcatgccgt tgaaacttac atattggcat 53640 agttttattt tcccatcata aggtagatga tattttaaag gtattatata gtaatagtca 53700 ccagaagcca attaaaacca ctaggattct atcaaaaacc tgtttggcgg cataaataat 53760 tgatatgtgg aaataaagca gcattctctg ggcaggggcc tcctgtacag acctgggtgg 53820 cgttagcagt ctctcttctg tgaaccaggg ggcgatttct gggcataata tcacctggat 53880 ttaaaaaact taataataag gccacacacg catttttaaa aaaacttccc ttgcctgtgg 53940 agacagagag gagatagcga tgttattttc aggtgtttga gcttcttaga gaaaaagaaa 54000 caaataccag actccttagg agctaggtgc gaatggaata aattgaggca ctccagcgac 54060 acatccagct tgttttaaat gatgtgatta aaaaggacat ctgagaacaa atttatgaag 54120 ttgttatggc aactgaaata cttggattga aatgtgtgta tctaaaacat gaaagattgc 54180 aggaagccgg agaaacaagc aaagcattgt gtttgggaaa ggcaattgaa cagtggtagc 54240 caaatattat tcctctgtcg gtcatccttc agggtaactg cctcggtttc cacttttaaa 54300 aacgtgtggt gattgatgct ttcatggact ctgttgcccc aagtccccaa gccttgtacc 54360 agcgtttgct cattggtcct ttgacctgtt gagaacacaa tctctgtatt gtgttcaatg 54420 cagggatgca tttagagttg cccctgcatc tacccattaa gtttatactc ctgtgttctc 54480 atattaacgt ctgtgtttgc gaatagtctc tctagtcttt gattcactaa ctcccccaat 54540 tctaacccac caatggccac caacaaacag ccacactcaa aggactcaac atatttaaat 54600 attccctaga attctttgct ctgttctaaa agctatgtat cccgtctaca taatttgatt 54660 ctattgtaat ttctcatggt tttaaaattt tccttaccag tacttgtaag agtattgaat 54720 aattgtttct ttcaatcaca ggcaaggata tttaaaatta acatgtggaa atgtgtgttg 54780 cagtgtgttg aaaaatcagt acttgaagtc acatctagaa tgcttccgat tttttccatc 54840 attagatttc agatgcagtg tccaaaaaaa ttgtttttaa aaaatgttgc tacaaatttc 54900 ttgcaatata ttttgggttt ttcactttaa atgaaaaaat agttaagtgt caattttagt 54960 gattttagta gaccatccca ttaaaaatat gctattttaa ttgaaaaaaa tttttgacaa 55020 aacacattta caccgaaaaa ttcaaacaaa ataatttctt ctttaacaat attgattgtt 55080 aaatgttgat taccaagtta tttggtctcc ttaattttaa gcataatact ctttactttg 55140 aatagtctta atccctaaag caaagcaaag taaaagagaa aaaaaagtag aagaatttcc 55200 agaaaattgt aattccctta aaccatgaat tagaactttt tactcttact gtagttactc 55260 tagttttttt agttagacat gagggtacaa tcaaacagct tcttttttgt aacagattgt 55320 tttcctactt cttgaaaaac tgagatcaaa acatttttct attctgttgc aaaattaact 55380 gttgttattc tgtcagacga gttattcact ctaaatgtct ttttaaacct gtatatttat 55440 ttttttatcc ctttttgcat atgcacatgg aagtgattcc attttaatat aactttttta 55500 ttttgaaaac ccataggttg aagatgatat aatcagagta ataataagga tgctccaagt 55560 atattaaaca taagaatttg gggtctttgt tacggaaata gatttccttt ttcctttctt 55620 tagtcttact gttttaagga ttttttttaa agtatgattt tgatgcttcc aaagtggttg 55680 ctattttatt tcaggtgggt catttgatag tttgttgatg ttttcaaggt ctctaaacaa 55740 agtctgatgt gttaacagtc ttattaacga tgttaaaata gaattaacag cttgtggatg 55800 cctccagagc acaatagcct gtcagcctcc cctgccccct tataaattgt gcccctgctg 55860 tcatcccttt gtttcaggcc caatcagcaa actaaacttt tgtgaagaga gaaggcagtt 55920 caagtgtttc tgccgcagct gaagggagga gctaatgtgg aatttattgg gagaccaatc 55980 agtgctggag ggaagaatga ccccaaattg gaagaaggac tttgttgacc cccttggctc 56040 cctgaccttt ccttgctatt ttgtcccttt aaagaggttt actttggttg tcgtttactt 56100 tgtgatgctt ttagtaaaag ccccagaagt tttaaaagtt ttggatttaa gatccctctc 56160 agcacagatt taattgtgcc gtgtgatttt gagtaacttg agtagatgtt aacactcaga 56220 attatttttt aaaaatctga cacaagctat taataatttt ttaaaggagt agaatttcat 56280 tgattctctt gagccaaaat agattctaaa tctcttctag tatctctttc ctgtagttac 56340 tttcatagag aatcagatta gttactgatg ttagactatt ggttctattt cgttgaattt 56400 atgctttaaa aaatagattt gtgtattcca aatctttaaa actttttttt tttttttttt 56460 tggtcaggca gtaattatag tgagtcagaa acaaatattt ttagaggaac cctttttttt 56520 tattagtatt actagtaaca aatttgacaa attgtcacat tttaaagtac agatttatgg 56580 gatagcctga caaatggata ccacttttcc tttgctactg tccaatttaa taatttataa 56640 agtgtggcat atttgtaaaa tagttaccca ttctcactga gcattacacc agttttggta 56700 agggatactg agacattgtt aagaattaag tattttttag attgcttgag cactttcctt 56760 gttcccttat cagcattctt ctcccttgta atgtggtttg ttgcttatat ttactttgca 56820 accggccact gttcaaggac ttcagacagt gctgaggtcc gagatggtca ctgctggtcc 56880 aaagaacaaa catctcaggc tagatgcagg acactaaata tgttcttcaa gccaaggtta 56940 aataaaatta ctcaaatgta gccaaatacg gggaatgaga tgcagttaat gaattgtggc 57000 tttgaaatat gatcatttgc caaggaatat gctgtgatga aaacggagca gtgtaaactc 57060 agcacttctc ttagctcgta gtgagctgct caggtaaacc ccgaggggaa tactttcttc 57120 tactgaataa accctaaaga taggcatcca ttgattgaac agtgtctgaa actggagcaa 57180 acagggcgcc gtttgatact agccccatgt gtgggtataa ataatgtttt ccagttggca 57240 tccttgagtt gtgctgcttg aatagggcca ctttacgtgg ctgaagaaga atgtctctgc 57300 agtagttctc cctgagcagt aactgcttgg tacctttcac ccacagcacc cattgctgcc 57360 catccccatc ccatgtctag tgtgccctca cattccactg ctggtcagca gaaccatctt 57420 atcagaaagt gtcaccaagc ccttttttgg tgtgcccgct gaatgagcac tccaggctgt 57480 ggagttcggg acatgccttg gtttgtgggg accatgctgc ctgcctgtcg agaccaagca 57540 tcgatactgt gtgtctacct gatgaaagtg tccagtatgt gtctgcatga cttggggaca 57600 ctaagaaaac caaagggatt agcaacaaag agagcttgtc acctttgtgc ggaagccagc 57660 tggcatctca cagggacaac ctacaacctg agctgctgcg tcctcactaa atctgggccc 57720 ctagggaccc cgttttactc ctgctctcct ggagcttatt acgggcctgg ctaccaaagg 57780 gaaagagggg aaaatagacc aggagcctta tgctagaacc atttattttg tttcacgtga 57840 tgcagacaga gataaaactg caaatttaat gaaactttaa caatcagtac aatgtttctc 57900 cttaagaact ttgtaaatag catttatctt tcaagagttc tttctctctt tttgtgatta 57960 ttttataaac ttaaaggaaa aagagaaaaa gtcagtggtt ccagcatttg ctttagtctg 58020 tgacttaaat ggattataac tcttgaccgc tgacatttac caagataaat cagtggtcat 58080 agatgtggag cttgatgtct cttcggctct gggaccaatc cccttggaca aaagttttcc 58140 tgtgttctta gtattctgaa ctggctacag caactttaag gaaaataaag gttacaaaaa 58200 aagttctgac aatttgtttg cttttacatt ttcaaatttg tgaaatgtag agataatttt 58260 gttttcaaat ctttgtaatt ccctgaagca aatactttca agccagttgc aaaatgctgc 58320 tttagaaata attcatataa acatgcttct ctatttaatc acaaggggag atgtggagaa 58380 tggatgtttt attttttcag tagtttttgc tctataaaaa tattaaattg ctattatgat 58440 tactaaagat acctttgcgt agtactttat aatttccatg tacttttata aacactatta 58500 catataatct ttgaatgagt tctgcaggaa gatattattg tcctggtttt gtaggtgaag 58560 aaacaataaa tgcacacatt cataacgtgc gacgtagtgc cagctttgta ttgccagaaa 58620 atcattttaa gaaatagatt tggtatgtaa aatggctaga aaacacaaca caaatttgga 58680 acgaagaagc tgttttgatt ccacatgatc tctataaaat atgaccaaaa aaaccgggaa 58740 aataaaatca tctgatcatg tgcaagtcct tttttagtac acaattaggt gaatcttgtt 58800 tttatgattg cttagttttc atgtttataa aataccataa tatgccccat aattatagca 58860 taataataaa ataggaaaat aacatcttcc ttttaatttt taagacaaat tataatcaca 58920 atattatagc agaagaatgt ttttcaatta aaaagtggtt tggttaaaat atgatttttt 58980 ttcttctaaa aatcccaaaa tggccaaaat atatttaaaa atatatttgt tatatatatt 59040 tttatttaaa aataattttt tctcccactt gttaaagatt aagtggcata agtatttgtt 59100 ttggggcaat tcactgccga cattcagaaa cagaactgta ttattgggca caggaaaatc 59160 tgattagtgt ttctaagaat tagtatagca cagcaagaca gggaagcagt ccaaagtgct 59220 aaaggttaaa agcaatttat aaaaactagg aaaagacctt acttgcttaa aaaaaaaatt 59280 tcttaataat taaaattgtc taagtgatat tcttgaatat tttttgtaat agtttcatat 59340 tattttcata aaaatacttt ggttgaggca gcagcagagg aggaagaatt aatataaaga 59400 aaacaaattt tcctattttg caagatccaa aatcttatga atatagtttt tagtgaaaaa 59460 aattattaaa cttttacaca gtaaccctaa gaaaagtctc cacatatggt cccaaaggtt 59520 aaaaaaaaaa acccaaaact cctctgggga aataatcatt tcatgaaaag cagtctattt 59580 ggaatttcac tggagacact ctgagaatcg aatcgagctt aatttctgtc tttgtgataa 59640 tcaaatatac attttgcatt ctagaagttt agaggaggta ttatatgtcc atggttttct 59700 ttaaacaact ctaacgtcaa aatggtcaaa ctgttggact gattcatgtt agataaaaca 59760 gatgggattc tcagatcgtg caccgttcag ccgtttgatg gaattcgcgc caccctgacc 59820 agcgagccca gatggcgctt aaatctgtca ctctttaacg accctactgt tttttaaaaa 59880 tatttttata tttgagctca ttcagttaat ctgagagatt aatcttttcc aagatatgtc 59940 tggggagggc tttactgagg gtttcacttg gaggagctca gggagagtaa gaagaatgat 60000 gaggcctctt ggacacagga ctacttgcta gaaggaacct ggggaagaag ggctggtggt 60060 ccttgggctt tggaatattt ttgaggcaac aaggcccaga agtgcacgtg aagagtggta 60120 gtgacggggg ttaagggaag aggggatgga tggggagggc gtggtgcagg gaggtggagg 60180 tgaacactga catcgctgag acagtacagc ccctgccaag aagcttagat ctcagtaagg 60240 ggccaagtgc tgactgtgac cacacctgag tggctttagg cagcctgacc ttcactgcat 60300 ggggatgact cggtgggtgt gccccaggag cagagcccaa gatgggctcc aatgtgataa 60360 gcctctggga tggctctgga aagaacctgt tctgcaccac aactctcaca aatctcatgg 60420 ggtttttttc cctgtaggtt ttttcccccc tttcttaaat tgttatttcg agccagtcag 60480 cctactgaaa tgcttcagtc atttggggtg taagatgttg gccagctccc gaatctctaa 60540 ccttggatac atttgcagag tggcttggaa ttgctttcta ttcctgctgg ggtaagaaag 60600 ggaaaaatga atgatttttc attatgcaca catggtattt tttcccgcat ttgaatcaga 60660 tgtagcaggt gtcaaaatat ggtacagaat ttacagtatt aatgtgaaaa tttctactgt 60720 cccaaaaagc caccagagat ggacaaaccc acctatgtta acaaaagtaa aaatgccctg 60780 ctgtctttaa agatgttcct ggtggtattt gggctgctct gtgctagttt ttctggggat 60840 cacgtgatgc tgcctatact tgggggtctt gtggaaagca gtggatgcct ctcaccctgc 60900 atagaagacg ggtccaaatg tcttgtgccc acctgagtgt ctacacactg aagacacgtt 60960 agaggtctgc tttagagagg ttttcctcct aaattaagga tctatgactt tcacatagac 61020 ccaaaagtga gcagagatgc aagttgtgtt gagaggttct tttggaagat gtggggcttt 61080 gggggtcttg gggactgggg gactgtcaga agtcactgct ctagtagaat gtggtgggaa 61140 cttataacaa cagattctcc acagaaatgc cacacgtaac catcccttga ggatggagcc 61200 acgtatgctg taaacagagt ggaagaacat caagctcgta acttgtcatt ttcatcataa 61260 atctgctgta agcttgcaac agccacggtt tccccctccc cacccacata cacataggga 61320 cattatggaa aggattgcag tatagtccta cttaaagaat cttgcttttt tttttttttt 61380 ttttttttag aaaataaaca attgctagaa gagtggagag accacttgca tctaactctg 61440 tggcaggttt aggattctgt gtaatcagta agacagagag ggaatgtgtc aactggcctc 61500 aatttcctag tagttttggg tgtttacaga gtacaattga acattttaag ggaagcaact 61560 tgtggtgcct gcattgaaaa tcattttgat gaagttatgg aatacatttg atattatcta 61620 aaaaacaaat ctcctacttt tttgactcag atatttctag tagtcaaaat aaacattcgc 61680 tcttaaattt tactagtcaa ctcatttcac attcacctga ttccctctaa aaacaaaaat 61740 ctttctacta ttccaattgg caaatggtct gttttggaac aaaaggatag atgcatttga 61800 agaattctct ggtcacctga gaaatgaagg tttgcccatc attttttatt aatgcttgcc 61860 aagtaattag gtatgaaaag atgaggagca aaaataaatc ttcatcttca atagaacatt 61920 agaggctggg catggtggct cacacctgta attccagcac tttaggaggc cgaggtggga 61980 ggattgattg aggtcagaag ttcgagaaca gcctgggcaa catggtgaaa ccctgtctct 62040 acataaaata caacaaatag ccatacatgg tggcacatgc ctgtagtccc agctacgtgg 62100 gaggctgggg tgggaggatc gtttgagccc aggaggcaga ggttgcagtg atccaagatc 62160 atgccactgc actccagcct gggcgacaga gtgagccctt gtcttaaaaa aaaaaaatct 62220 ttaatagaac actggcggcc gggcatggta gctcacgcct gtaatcccag cactgggagg 62280 ccaaggcagg tggatcacct gaggccagga gttcgagacc agcctgacca acatggtgaa 62340 accccatctc tattaaaaat acgaaaatta gctgggtgag atggcagttg cctgtgaatc 62400 ccagctactc gggaggctga ggcaggagaa tcacttgaac ctgggaggcg gaggttgcag 62460 tgagctgaga ttatgccact gcactccagc ctgggagaca gagcgaaact ccatctcaaa 62520 aaaaaaaaaa agaaaaaaag aatattggct atttgagcaa gatgaatgta ttttggtaga 62580 tagaagaaaa atgagaacta tcgctcatca ctgctgatgt ctaaatcccc tccctgggca 62640 tgaggatggt acaatgacac agcaacccca gcctgccggg cttctgggat gccaagctgg 62700 gggtgtcctg gccaggtcca aggtgctgga agccaatcca gaaaatagga tgaagggata 62760 aaatcacact ccaaggccgt gatatgattg aatcaaggtg ttaatctagg tgaagagtgc 62820 agaagccaga ttcactaggg gctccagggc aggacaagct ggttcagcgg ggagaaggca 62880 ggaggcagat gcccaagaag tgtgggcaga tctaggggtg actttatagg ccctcagctt 62940 tttttttttt ttgagatgga gttttgctct gtcaccaggc tggagtgcag tggcgcgatc 63000 tcggctcact gcaacctctg cctcccaggt tcaagcgatt ctcctgcctc agcttcccaa 63060 gtagctggaa ctacaggcat gtgccaccat gcccagctaa tttttttgta tttttagtat 63120 agaagggatt ttaccacgtt gaccaggatg ctctcgagct ctcaacctca tgatctgccc 63180 gcctcagcct cctaaagtgc tgggattaca ggtgtgagct gccgcgcccg gccaggtcct 63240 tagctttgaa tggggagtga ggcattaggg gcatggagac acgtgaagaa catgtagctt 63300 gtcctttctt ccttccagag ctttctctag ccatttgcaa aaattccaca agcacattat 63360 gcagtcattt ttctaggaac tggagagagg ggagaggtgg atgggagggg agggtgtcat 63420 aagccttgaa aaagttagat attccaaaga accttagctt ttcccaaata ggaaatggag 63480 agttgggtgg tagtttcaaa tcattatttc attttcttta cctctgaaaa gatttcttag 63540 tttactgaga gcctaccttc aattgcatgg atgttgtaca ttttcttttt catttcccat 63600 gaagatccct atttttagct tttaagagct gttactcaca actgagatac aaacagtgtt 63660 ctgcacccca cacagcatat atctcatgat tagtgacagg gttcctagaa ctgcaagaca 63720 agtttgggct tactcaatct gttaagtttc cttataggca tattttttca ttctattgtt 63780 ttagcaaggg gcctattaga aatttccatg tgtataaatg acactttaaa gagctgggtg 63840 caggctgggc gccatggctt acgcctgtaa tcccagcatt ttggaaggcc gaggcaggca 63900 gatcatttga agtcaggtgt tcgagaccag cctggccaac atagtgaaac cccgtctcta 63960 ttaaaaaaaa aaaaatgaaa attagccagg catggtggca tgcacctgta gtcccagcta 64020 ctcaagaggc tgaggtatga gaattgcttg aacctgggag gcggaggttg cagtgagcta 64080 agatcgtgcc actgcactcc agcctgggtg acagagcaaa actccatctt aaaaaaaaaa 64140 gagctaggtg cagtggtgca tgcctatagt cccagctact tgggagactg aggtgggagg 64200 atcacttgag cccaggagtt tgaggctata gtgagctatg attgcgtctg tgaatagcca 64260 ctgcggtcca gcctgagcaa agtagcgaga ccctgtctct aaaaaagtaa aaattaaatt 64320 taagaagttc ttcaccatcc aagttatgtt acgtggaatt tcccgtggca gtttcctgaa 64380 acataacttg tttatgtttc ctgaaacaaa acttacctgc agtttctaga cacgtgctct 64440 aaaaacaggc atctactggc ctgttttagg atttagaaat ctctgctctg cccttctttc 64500 aactatccaa atgaaaagaa tgttttaaca tttcatattt gtgaaagttt cctcaattac 64560 tgactttttt cagttttaca atttgttttt ggccaaaaca acagcaacaa caaaaatacg 64620 atttaactgc aaaattgacc ccctgatctt agctacacct tccgtggtcc ttttctacca 64680 ttcagcttga ccctccaccc atgggaggtc tctgctcatt gggaatactg ggccatgaaa 64740 catctcaata ttttccatgg tctttacttt atgcttgctc ctcttctgtt cttcatacag 64800 caagccagag aatcagatca tgtcacttcc ctgcatatct ttcaaaacat cccattgaac 64860 ttagaataca atccctcctc cttactgtgg ccaccaaagc cctgcattgc tggctcctgc 64920 tgacctctcc agcaacatct tatgccactc tctcccttgt ccgctgccct tatgacacac 64980 cggtctcctt tcagtgcctg cggtatacag cgagctagtt cctgcctcag ggttgttgca 65040 ctagctggtt ctgctgccag attctttctg tagctggctc cttgtcctct tgaggcccta 65100 aagccttccc taccatccta ttttaggact cttatcctca accccctgcc atgattctct 65160 ctcacagcat cctgtttctt tccttcatgg catttatcac agtctgtcaa tttttgtttt 65220 ttgttttctc gtataatgtt tgtcttccct actgcaggcc aaagagtttg agctgagcag 65280 ggagttgcta ctgaaagtgt ttgatcaggg gagggtatga ttgcacttta aggagattga 65340 tctatagcca tggacaaaat agatttaagt gcttggtgaa ggcaagggag agactgaaac 65400 agaaaagcta agaatagaaa actactgtag gctgggcacg atggctcaca cctgtaaccc 65460 cagcactttg ggaggccgag gtgggcagat cacttgaggt caggagtttg agaccggcct 65520 ggccaaaatg gtgaaacctc acctctacta aaaatacaaa aattagccag gtgtgatggt 65580 gcgtgcctgt aatcccagct actcgggaga ctgaggcagg agaatcactt gaacctaaga 65640 ggcagaggtt gcagtgagcc aagatcacgc cactgtactc cagcttgggt gacacagcaa 65700 gactctttct caaaaaaaaa aaaaaaataa taaaagctac tgcaaaagtc ctcctagtag 65760 gtgacaggga ctcaaactgg taggtgagaa gggatgtgtg agagactgcc cttgtgcctg 65820 gactcacgtc cctgacttgt gcacctccct cccaagcaca cagtcccctt ctcacatcct 65880 cgccctcact ccacccttca ccgtctcctt ttgggtgtca cctctgaggc aggcactaca 65940 ggccttctgg gtgattcttg agtgatgggt atgtctcaca tctttttgtt gatgatacag 66000 ttcctttata cagagctgta ttgttattag ctgtcgtccc tcttgttaga gcccttctca 66060 aggaagaata aatacactgt aggtgactag gtgactcctg gaatcttttc ttcgggaatt 66120 tctttttttt tttctttttt ttttttttga gacagagtcc cactctgtta cccaggctgg 66180 agtgccagag tgcagtgttg cagtcatagc tcactgcgac cacaaactcc tgggctcaag 66240 tgatcctccc acttcagcct ccagagtagc tgagacaaca ggcatgcact actgtgccta 66300 gctgcctatc agtttttctt tactgggtaa gtataaatat ctaaacatcc acaagacatg 66360 gaattgagag tctcttttct ctgtcaccta gtgtatttca ggtctataat aaatattata 66420 cagggctggg tgtggtggct cacaccgata attccagcac tttgggaggc ttcagcaagt 66480 ggatcgcttg agcccaagag tttgagacca gcctgggcaa catggtgaaa ccccatctct 66540 accaaaaaaa aaaaaaagtt agccaggcgt ggtggtgtgt gcctatagtc ccagcttctt 66600 gggaggtgtg aggatcactt gagcccagga ggttgaggct gtagtgagct gtgattgtac 66660 caccacactc cagcctgggc aacagagcaa gaccctgtct caaaaaatat atattaaaca 66720 gcaacaataa cattttacct catttttctc cactgttcat tttgtttgaa aatctgtgtg 66780 gcaaaactct atgcccttaa cccttaaagt tgccattagc cagatgatgg caggggaagg 66840 gcgcatggga tcttcagcag tccttcatcc atgcgcccaa tgggtattga ggagccacca 66900 tgttcagggc actggggaga tccatccatg aacagaacca aaatctgccc ccctagagct 66960 tacaattcag caggctgatg gtaacaacag agataaataa gttggtcatg gagaatttta 67020 gaaagtgtcc agtgtcatgg tgcaacagaa aaggtgcaac aggggccagg catggtagct 67080 tagcctgtaa tcccagcact ttgagaggct gaggtaggca gatcacctga ggtcaggagt 67140 tcaagaccag cctggccaac atggtgaaac cctgtttcta ttaaaaatac aaaaattagc 67200 cgggcatggt ggcgcacacc tgtaatccca gctactcaga aggctgaggc aggagaatca 67260 cttgaacccg ggaggcagag gttgcagtaa ggtgagatag caccactgca ctctagcctg 67320 ggcgacagag cgagactccg tctcaaaaaa aaaaaaagaa atggtgcgac aggggcaaag 67380 gaaatgaggg gaggcaggat gctattttaa atagggggta aggataagcc ccattgagaa 67440 ggtaatatct gagcaaaagt ttgaaggaga ggaaggactt agccttgaat acttttgagg 67500 aagaatggtc taggtagagc agccctgtgt gtccgtggtt agcagggagg gctgtgggct 67560 ggtgtgaagt gagaggggtc cacagcaatg gaggtgagac cagaggggga accagaggcc 67620 agatcgctgg aaggatgttg gctttactcc aggtggaatg aggagccatt gcagagtttt 67680 taaacagatc cctccagaag ttatgttgag aataccatgt aggagacgag ggttgaagtg 67740 gggagacccg tcaggagata gttgctgtga gacaggtgag agctgctggt gtctcaaact 67800 gagtgagatg tacctgggat atgtttcgaa gcagaatcaa tgagatttcc tggtgggttg 67860 agtgtttctc agttggaaat aaaagaggag tcaaggatga ctgtcaaggt ttttggtttg 67920 tgtgactgga gggaaagagt ggctttcaaa atgggtttgg caataaatgg agcacgcttt 67980 tgttggggta ggggtggagg tcaagagttc agctttggac atgttgaatt taagatagct 68040 actagaattc gttttttttt agctactaga attctttttt tttttttttt tttttttttt 68100 tgagatggag tcttgctctg tcacccaggc tggagtgcaa tggtgtggtc ttggctcacc 68160 gcaacctccg cctcgcaggt tcaagcgatt ctcctgcctt agtctcctga gtagctggga 68220 ttacaggcac gtgccaccat gcctggctaa tttttgtatt tttaataaag acaggggttc 68280 accatgttgg ccaggctggt ctcgaactcc tgacctcgtg atctgcccat ctcggcctcc 68340 caaagtgctg ggattacagg cgtgagccac catgcccagc tgatagctac tagaattcta 68400 agtggaggta tgaagtaggc agttttgggg agagaggctg ggtctggaga tgtacgtgtg 68460 ggagctgtta gcagagaaat ggtatttaaa gtctgggtgg ggtgacttag gaatggacac 68520 agagctgact gagcagtcac accccgtttc cccacgaaga cctcagccca aggcaaccac 68580 taatctattt tctgtcttaa tgttggacac tccaacatta agggatgcgt aagaagaagt 68640 ggagggggaa ccagcaaagg agatggagaa gtcatgagca gtaagatagg atgattacca 68700 aggagtatat gtcctgggaa ccaagtgaaa acagtacagc aagttgggag ggggtgattg 68760 caccagatgt tgctgccact gggtcagata attaggaaac caagaatcga ctattgaaag 68820 ctggatgcaa tggtgcttgt ctataattcc agccactcag gagactgaga tgcaaggatg 68880 gcatgagccc aggagttcga ggctgcagag aacaatgatc gctcctgtga atagctgctg 68940 cattccagtc tgggcaacat agccagacca gaccctgtct cttaaaaaaa caaaaattgg 69000 gctattggat ttagccacgt gggggtcatg ggtgaccttg acaagagcag atttggtaga 69060 agcatggaat ggatttttcc taatattcct cctcttcagg ggcagacaat atttaaatga 69120 aaccgtattt ggagcactca tcaggcttta atattgatgc tgcatcttct actgtcacat 69180 acataaaggg gaccaggacc actgcattac agatgtgact atttctacct tatatatgta 69240 tgccctatat gtgtatatac tttatgtgtc tatatcagct ttattgagat ataatttaca 69300 tctcatacag ttcacctatt taaagtatac agttcaatga atttaatggt ttttagtcta 69360 ttcagtgtta tgcaaccatc accatgatta attttatttc tatcactgtt tcttcagccc 69420 caaaagaaac cctgttccca ttagcagtca ctcctccttt tcccccaaaa ccctcagtcc 69480 taggcaacca ctagtctact ttctgtcttt ctatatttgc cgattctgga ctcttcatat 69540 acatggaatc atacgatacg tggtcttttg tgactggctt ctttcactta gtataatgtt 69600 ttcaagcttc atccaagctg tagcatgtgg cagtacttca ttccttttta gggccaaata 69660 atattccact gtatgtacta atatatacca cattttattt attcattgat tagttgttgg 69720 aaatttaggt tgtttctact ttttagctat tatgaataat gctgctatga acatttctgt 69780 acacattgtt gtatgggtat atttcttctg gggttatact taggaatgga attagaatgc 69840 agtagcatga tctcagctca ctgcaacctc cacctcccgg gttcaagttg ttcttgtgcc 69900 tcagcccccc aagtagctgg gatcacaggc actgtgcctc cacgcctggc taattttttg 69960 tatttttagt agagatagag tttcattatg ttggccatgc tggtctcgaa ctcctaccct 70020 caggtgatct gcccgcctcg gcctcccatg gtgctgggat tacaggcgtg agccaccacc 70080 cctggccaca gactggcttc cttccttccc tccgtccgtc cttccttcct tccttccttc 70140 cttccttcct tccttccttc cttccttcct ttcctccctt tctttttctt tttctatttc 70200 tctttctctc tctctttctt ccctcctctc ccctcccctc ctgtcctctt ctctctttct 70260 gacagagttt cactcttgtc acccaggctg gagtgcaatg gcgcaatctc ggctcactgc 70320 agcctccacc tcatttgttc tcatgtctta gccactcgag tagctgggat tacaggcacc 70380 tgccaccagg cctggctaat tgttttttta gtagagacag gatttcgcca tgttggccag 70440 gctggtctca aactcctgac ctcaagtcac ctcagcctcc caaagtgctg ggattacagg 70500 catgagccac cacacccagc cttcttcatt cttttttttt ttgaggtgga gttttgctct 70560 tgttgcccag gctggagtgc aatggcacaa tctcgactta ctgcaacctg cacctcccag 70620 gttcaagcga ttctcctgcc tcagcctccc gagtagctgg cattacaggc atgccccacc 70680 actgggtgaa aaatgcccag ctaattttgt atttttagta gagatggggt ttctccatgt 70740 tggtcaggct ggtctcgaac tctcgacctc aggtgatctg cccacctcag cctcccagag 70800 tgctgggatt acaggcatga gccactgcgc tcggcccatc attcttaata atattcccaa 70860 atggtgtata gataaatact gccacaattt caggactaga ggttaaaaaa aaaaaaagga 70920 caaagttgga cagtagagct gagagcacaa attgtcccct ttttttccca ggtccttagg 70980 ttcgtagacc tgtgtcagcc ataattactg ctgaatgtga ctcctgtgta tacggtcatt 71040 tttatttttt ctgttcctgg aggtaatgca ataagtcacc tcaaaaaggg cagagaatga 71100 gggagagaat ctacctgcat tggcgtattg aaaagatcag attatttcag aatccagatc 71160 attgtttact tttagctgca taaaaatatc caagtagatt ttcttataac ctctccaaga 71220 taaagatgcc agaaacggca gccaaataca ttgactttga gagaggaaaa aaaaaaagct 71280 tgtaattgcc gatcactcct tagatttact tctggggagc atcaattaaa aatctcaaaa 71340 cacgtggctt tttcagtaaa attatattaa tatggaggaa gagtttttat taaatatgag 71400 tgcacgtgtg tctgtgtctg tgtgtgtttt aaacgtttcc ataatgagtt cccaagtgct 71460 tttttggcag tagttattaa agcttgtgtg tttgcgattt atctggcaaa atgcctttag 71520 tgaagaaagg atatagtgtt ctcttggttc tttgcccaaa gtaattttgg agaaatctgt 71580 gactgtattt agttcatgtc attcattgga gacaagtcat tgtaattaca tttgatcaca 71640 atcagtttac agttgtttta tcatgttttc atgctgaata tctactcaga catcatagca 71700 aaatttaatg gctactgttt tatttgtaca taaaaagatt tatagccctt ttttgcagta 71760 cacatcgggt ttcaatcatc actgctacag agtgagagga aagctatgga taaagaacta 71820 tcagaaatcc ttgactacat aaaattttat ttcaggtcac cttgccataa aagatattga 71880 atgtattttg tggcttttcc tcctgacatg ctaaccgttg tagaagagtt gcaatatttg 71940 gaggaaaccg tatgaaatgt ggaacttaat tcacttaaga tggtttacat ttgcgcgtgt 72000 tttccactgg aaatagccat gccagcctta tgaatggccc ctgggtaatg cagagtaaaa 72060 ggcaatggca ttaccgatat tgttgagttt taaaaggaag ttgtcttctt aaccatacgg 72120 ctgaacattt tgtcattgtt gtttcagaag gtctgctcta acatctgcac tgcggcagag 72180 ttgtgttaca gggtgttatt tacagctgcc aaatgctgga ggctctcatg tatcagacag 72240 tctctgattt gctaattgtg gaagccttga ttcaccagtg aatttgggta aattcactag 72300 ttatctccta agtgtcactt ctcaccatgc cttatttttc ccaaaaggtt gattccaagc 72360 tctgctgaaa tctgctcttg gtctatatgt ttgagtctac attgttgaag aagctccctt 72420 tagaaaagtg taattaatgg gaaactttga catccagctg agaaaattag tttgcatcaa 72480 aaaaggcaag atagaggatt aaagaaattt tagtcctaat ctaattaaca ccaattaaaa 72540 gatgcagatg aatttacacc aacaaattgt taattatgca ccaatttgcc ttttttctgc 72600 aaccaaactg aaatcaggaa agtattatta tcttttttgt ttgaggagac ttacattgtg 72660 ggtttgttac aatcatcttt tatataatta aaaggtaggc agaaagagcg tgaaatattt 72720 cagtctcctg acattttaat ttaggttaac tctttaaaaa tacaaagtac agaaaaaaaa 72780 aattccagaa agtacaggat aattctatta gcatttattc actgactaga tatttattga 72840 ggacctagta tgtgctggac acttaggtaa ccattgtttc tctcactcaa aatattttaa 72900 cttgtttgta tttctaatat attgctcatt agaaaaattg tatacgccag gcgtggaggc 72960 tcatgtctgt aatcccagca ttttgggagg ccgaggcggg cagatcacga ggtcaggaga 73020 ttgagatcat cctggctaac acggtgaaac cctgtctcta ctaaaaatac aaaaaattag 73080 ccgggtgtgg tggcgggcgc ctgtggtccc agctacttgg gaggctgagg caggagaatg 73140 gcgtgaaccc gggaggtgga ggttgcagta agccaagatt gcgccacagc actccagcct 73200 gggcgacaga gcgagactcc gactcaaaaa aaaaaaaaaa gaaaagaaaa agaaaaatag 73260 tataagctaa ttgtaccaaa attgtataag ctaattaaat tctgccctgg atacatgtca 73320 gaaaaggaga atcgaaattt tgggcctcaa gaaatgctct taatgtccca gaactcctct 73380 ttaatgtgac cttttagggt attcagcgtc catcttcctc acccggggaa tctgtgtttg 73440 tttcccagtg ttactcagat ctccactgtg ctgggacttt ctttttcctt gtgaatcact 73500 cttacagctc ctcagatggt gatctgagta attatgtaga gggtggtgaa gcacagacct 73560 tttagatctg caaatgacac atctgtccaa atgtcatgta atgagtaacc acaatccact 73620 ttatataagc catatttctt ctctttccaa aatgggaagg agagggtggg gggggaaatg 73680 tctggtagaa atgggaagaa aagcatttct atggattcct ctagccatta attacataga 73740 aaatgccaca gctgccctca gatttccagg tgcacgttat taaacgtcat tcaaaggaaa 73800 tgtttggcca actagatcct gatgtgagaa acagcatcct aaagagctat gtatgttact 73860 gtctaatgca tgtacttagg cattaaataa tattaaatga ccatattacc ttcttggggc 73920 aatagttaat ataaacattt aggatgctca gtttgtactt ttcagtattt gtgctggaaa 73980 cttttgcatt cacaactttg aaaactggct cgtgttttca tgggaagtgt cagtttaaag 74040 ttggcctact aattaatggg ggaatttcaa tatggcagtg cctatgacag caaatgaaaa 74100 gcattcttta taaacatcgt cttcctccac acattcacag gttagtatct gacacccatt 74160 tttaatttct agagcaccat ttgtacttct ctgtggtttt gcctgcaagt cttcgatgat 74220 gcagtccacc cttccataaa aacgtactcc aattttccta gattctactt tcattgtttt 74280 gtgaatcaag ttagaaggta cataacttag cctgatgaga tggcattcat aaggttagga 74340 tagcagagtt gcctaactaa tcttcctgtt gcaatgaaat aaaagaatga tatctaagtt 74400 gaccaacctt gtaaaaggta attttacaag aggcctccaa aaataacgga ctaggactgg 74460 ccagagaaga aaataaaccc ctcatcctca atccagaacc cagagtttgt catcactagt 74520 cgaaaagctt gtttgtttta tacctaagtg agaccttgag ttatccaatg tgcttccatc 74580 acagaatggc ccaccagggt agaaggattc tgagtgtatt ccctgatgct gttgccatgt 74640 gcctatggaa tacctatgct ccatatttag ccctctttct gtgtagtagc agagacgtgg 74700 atggctgctg aaactaaggg cccagtcttt ggccttagga cagaccactg ggtttctccc 74760 actgcctaaa accttagtag cattagcatc agacatggac ccaataaaca aactacctag 74820 ttgataagcg ccgcattttt catgatgttt tactgtggcc tatccacaca ctctttccta 74880 ttccatgaaa ggaagaaaaa gataatttga gttgtcctat aaattaaaat ttttcctttg 74940 tgattatttt ggaccagcgc cataacattc agaagattat gagtggagtc tttagtctgt 75000 gaacaaagtc ctaagaagga agtagtgctg taacttactt catctaaaga agcatcatcg 75060 ctgaatgtaa agagtgattc tggattggat cttaagccgg aaaaataaat ggagataaag 75120 tacgttattg ggataatttg tgatatttaa ataaggcctg tagaatagat actagtatcg 75180 tacccatgtt acattttctg atttggataa ttgcaataaa gttgtgtagg agagtgtcct 75240 tggtttgggg aaccatttaa gagtataggg gcacaatgaa tataacttac agatggttca 75300 cggaaaaaat acaggtgcat actatataaa aataaattta tatctgcata tattatgcat 75360 atctacctat ctatatctgt atttatacat atggagagag agagaccaag agagacagag 75420 agagcagtaa tgataaagaa atgtggcaga atgttagtgc taacagttgg taagactggg 75480 taaggagaat tcaggaatta tttagctatc cttgcatttt tatttttatt ttttttgaga 75540 cagagtctcc cactgtcacc caggctagag ttcagtggca cggtctcggc tcattgcaac 75600 ctccaccttc cgggttcaag cgattctcct gcctcagcct cctgagtagc tggggttaca 75660 ggcatgtgcc acgacgcctg gttacttttt gtatttttag cagagacggg gtttcaccag 75720 ttggccaggc tggtctcaaa ttcctgacct caagtgatcc acctgtctcg gccccccaca 75780 gtgccaggat tacaggtgtg agccaccact ccctgcctcc ttgcatcttt tctgttagtt 75840 tcagattaca gtcatgtgtc acttaacaat gagaatacgt cttgagaaat gcatccttag 75900 gcaatttcat cgttgtgcta ccatcacaga atgtatttcc acaaacctag atgttacaac 75960 ctaccgcaca cctaggctgt gtggtatggc ttattgcccc tctgacataa acctacacaa 76020 catgtagcta ctgaatactg taggcaattg taacacagtg gtaaggattt cttttctttt 76080 cttttttttt ttggagacag agtctcgctc tgtcgcccag gctggaatgc agtggcgcag 76140 tctcggctca ctgcgtcctc cacctcctgg gttcaagtga ttctcctgcc tcagcctcct 76200 gagtagctgg gactacatgc gcctgccacc atgcctgact aatgtttgta tttttagtag 76260 agatggggtt ccaacatatt ggccaggctg gtttcgaact ccagaccttg tggtctgccc 76320 accttggcct cccaaagtgc tgggataaca ggagtgagcc accgcgccca gccaggggta 76380 aggatttcta tatctaaaca tatatgaaca gaaaaagggt acagtaaaaa tactgcataa 76440 aagatttaaa atggaacact cacagaaggc tcttaccatg aatggagctt gcaggacctc 76500 atgttgttct gggtgagtca gtgagtgagc agtgagtgaa tatgaaggcc taggacatta 76560 ctgtcactac tgtagacttt gtaaacacta tatacttaga ctatactaca tttattaaaa 76620 aaaacaaaaa acttttcttc agtagtaaat taaccttagc ttactataac attttttttt 76680 tcttttgaaa cggagtctca ttctgtcacc caggctggag tacagtggcg tgatcttggc 76740 tcactgcaat ctcagcctcc cgagttcaag tgattcttct gtctcagcct cctgagtagc 76800 tggcactaca ggcacctgtc accacgcccg gctaattttt gtattttcag tagagacggg 76860 ggtttcgcca tgttggccag gctggtctcg aactcctgac ctcaggtgat tcacccacct 76920 cgccctccca aagtgctggg attacaggtg tgagtcacca cacctggccc aactttttac 76980 tttataaact ttatatatat atatatgttt tgttttgttt tgtttgtttt tgagatggag 77040 tcttgctctg tcacccaggc tggagtgcag tggcacaatc tcagctcact gcaacctctg 77100 cctcccacgt tcaagcaatt ctcctgcctc agcctcccaa gtggctgggc ttgcaggtgc 77160 ccccccctac accaggctaa tttttgtgtt tttagtagag acatggtttc accattttgg 77220 ccaggctggt ctcgaactcc tgaccttgtg atccgctcac ctcagcctcc caaagtgcta 77280 ggattacagg tttgagccat cacgcctagc ctgtaaactt tgtttatatt tttaacttta 77340 tgactctttt atagtaacag taagtttaaa acacacattg tacaaaaata tttcctttat 77400 ctcttattct atatgctttt ttatattttt aatttttatt ttttatactt tttgaacttt 77460 ttgttaaaag caaaaacaca aacacataca ttagcctagg cctacacagg gtcaggatca 77520 tcaatattac tgtcttccac ctctacagct tgtcccagtg gaaggtcttt aggggcaata 77580 acacgcacag agctgttgtc tcctgtgata acaatgcctt cttctggaat gcctcctcaa 77640 ggacccacat gagtctattt tacagttaac tttttttttt tttaataagg aggcgtatag 77700 tctaaaatga agataaaatg taaagcataa tataaaacca gtaacattta ttattatcaa 77760 gtattatgta ctgtgcatgg ttgtattgct atatatatat aaaatttttt ttttttttga 77820 gacagagtct cactctgtca cccaggctgg agagcagtgg cacaatctcg gctcactgca 77880 agctccacct cccaggttca tgccattctc ctgcctcagc ctcctgagta gctgggatta 77940 caggcgcatg ccaccatgcc tggctaattt tttttttttt tttttgtatt tttaatagag 78000 acgacgtttc accatgttga ccaggctggt cttgaactcc tgaccttatg atctgcccac 78060 ctcggcctcc caaagtgcta tgattacaga tgtgagccac cgggcctggc atgtttgatt 78120 tttttttttt ttttttttga gacagattct ctttctgttg cctaggctgg agggcagtgg 78180 cgcgatctgc aacctctgtc tctcaggttt gagcaattct cgtgcctcag cctcccaaat 78240 agctgggatt acaggtgcgt gccaccacac ccagtttatt tttgtatttt tagccaccgg 78300 gcccggccca gtataatctt atgggagcac tgtggtatat ttggtctgtt gttgacctga 78360 aagttatgtg gcgcatgact gtatctaaaa acaaacaaac aaaaaattta aatagaaaag 78420 ctggattccg accacatgaa tgaaccttct tatgattctg gaaggaaggc aggttctact 78480 aagacagggt tcttaggcta ctaccactac ctcacccata aaggatcagc cttcttaacc 78540 cagccagtca caagggattc tgaggatgaa tgttcaccag ggcagattgg ttatgttcaa 78600 cagcttcatg tatttctgca aaatctacca gtccgatgat gcagtgaaca taatgatccc 78660 ctgtgaaata ataacaagat aaaatgttcc caggcccatt tgtttcccac tgctaccacc 78720 ccataagact gaaccatggg ttggagtgaa cacttgaacc aaaggttact gtattgtatg 78780 ttcctgttca cacaggactt cacaaaaacc ttcttttata aagaaaacaa ccagccaata 78840 aaacagcatt agagtacatt atatatgtga ccaattgttt gataaaatct gatgtaagcc 78900 ttcaggcgta attggagttc ttagcaaaat actttggttt ttaatatttc tatgaccctc 78960 taagggggac ttagcaatta ctcttaaatt ttcaaagtgg tgcatggagt tttagctgtg 79020 tgacttccat taaagtccat aggagtcttg ttgctaaaac atcacacaac tcacgaaaat 79080 gtgccccttc ttgtgaaatt gttagaagta atgggtatgg aagtatagca cagcatttct 79140 ggtacattta caagctttct gtacttgttt caaactttat acctttatga aaactcaata 79200 gttctacaaa aattgaaggg gggaaaaagc ctattatgtg tattccagaa gtgaagggta 79260 gaaaaaatac agtagaacta ataaaaaatt aaaataattc ttcaagaaaa gccaatgttt 79320 caacatattt ataatcttta tttcaaaatt aatatatcct ctcctgggtt tttaaagtaa 79380 gccttaaaat cgaacttaaa aaaatgaact tgactgacaa agtttcacta taaccacata 79440 caatgatttt gggtttcagc aacctcctct actgaaaccg atataattta agcatcatcg 79500 gagcaaaact tcactccttt agatggttgg tggtgtgagg ggtttgttcc cagtggataa 79560 gaggatggcc ttaaggtttg ctgagtcctt ctctctcaag aacctcttag aggccgggca 79620 cggtggctca agcctgtaat cccagcactt tgggaggcca aggtgggtgg atcacttgag 79680 gtcaggagtt cgagaccagc ctggccaaca tggtgaaacc ccgcctctac taaaaataca 79740 aaaattagct gggtttggtg gtgtgtgcct gtaatctcag ctactcgggt ggctgaggaa 79800 cgagaatcgc ttgaacccgg gaggtggagg ttgcagtgag cggagattgc gccattgcac 79860 tccagcctgg gcgacagaac aagaccctgt ttcaaaaaaa agaaaaagaa tctcatagac 79920 atttttctcc tgcgtccctg tgataagagt gctgtgattc ctgctataca gtcaaacaga 79980 ttcagagccc acctttgact ccaggaccaa atttccccct ttattctctt ttgtgctatg 80040 ctggagaaga cagtgtggca gttcccggga atttgtgtgg agctgtttca gggacactct 80100 gagctaagaa aagggtgaga gccctgggag gagaccttct ttcaatccag gctacatgct 80160 ctgagttttt ccagggcata tatagctgct ccatttggac tatgctccta gactgacatg 80220 ggcctgactc gcaggagccg gcagctccta gtgctgagct caccggctcg gcccagcacc 80280 agcaccacct cccctctgag catctggtgg ccttgctgat aacacagtga cacagccatt 80340 tccttctata gcagaaacat ctttggagtt ctgtttccac agtcctttga gagacactct 80400 cgaggccagg agctggcctc agacataaaa gtatttgttt caacagagag agagagagag 80460 agagagagac tcagtgactg ctttttgagt gaattgttgt tggctcagtt tcagtaatgc 80520 aatgttttgc tttagattaa tttactaagc agtactaaag tatcatttat atacattatt 80580 gaatcttggg atgattctgt aagcattact ttctcctgaa atctccactt ctgtctggat 80640 agtggatttt aggataggtt tttaaaatgg aaaacttgac gcagattcaa attttcaaca 80700 cagcattgaa cgaatagcat cagttgggga cgagctatgc caccaattta aagtgtctca 80760 gccggggtca gaattaggaa ctgtctaaac agggaatttc agaagggcag gggaggatat 80820 caaggcacaa atgggaggaa ataagccatt gttcctttag aaagcttagt aacctcgata 80880 atgagaggct atgaaatagt tctttttata actgtaactt cttaacttcc cagccctaat 80940 agctccaagg gtcacttgca gagagctccg gggctacacc tgccttgcat agattagggc 81000 ccgctgcagc tgtcttcatt tgcaagacta aggtgtagct ccaagaggct gtaggtctca 81060 gcatggagca ctcctcctca atctcaatag gctggtgttg cggattaaga tggccattgc 81120 aagccaggct cagaaattgc aagatgaggc aggtaacgat ttcctgggtt ttatgtatca 81180 ggccttatga ggtatgaagc gggaaacctt ttatatgcct gccttgaatt agccatacct 81240 tttacaatca gctctgttga agagcagctg cctggactat ctagcatacc catgggccag 81300 gcatgccttt ggcacacaca caggtttgta aagagcttgt gaatctatag gatgatctct 81360 tggtgaggac agaagggacc catagctagt cagcatcgga ctgagggctg gatccacttt 81420 ttcctgtaat gtgcgtttgt ttcacagaaa atacaattag gataattctt gtgtgttctc 81480 tacaggaagg aagtagtata ctgcttgtga atggtaggct aaatgaggga accattaaag 81540 ggtttttaat agacttttga accaaaagac ataagggact atacttacat tgccttaact 81600 gagaaatgtt ttgcagtgtg agaagactta atcaaatctt cattacatac ctggtcaggg 81660 accaggctga atgtttcttt aagcaattgg ataaaatgca cattgaagac ttgttagtta 81720 tgtgagaata tgtctgacat gcttatcatc tctcctgcgg gtgcctgagt atcagatact 81780 tggtttactg tgttgggttg aatgcttctg ttctaatttc taatgaactt taccaccaga 81840 ctacttgatc atgactaagc ccaggaacaa tgcaaatgga attgccccct gatggggagg 81900 aatgggccca gatggccctt aaaaggtgat aattaggaaa tatagcatat ctgagtagct 81960 agaaagagag aaacttgtta aagacagtca atctgtttga agcaacggtc tttcccttaa 82020 ttatatgcat tttcatttag agttgcttta aagtaaaatt tttcccagga aaaattttta 82080 ttagtagtga aaacctagaa accacacaca ttttttgcta ctctgtttca gattattgaa 82140 aattccttcc ttcatacatt tttttttggt ttccagatct gtgtaacaga ctcgctgtgt 82200 gtgttttagg ggccgtttta ggttatttta gctcttatgc taaaacagtg ggggagcgat 82260 taaaagtgag aaaaatatta gtatatattt gtaaactgag cttttaaaat taaaatagtt 82320 gcaggatatt acagtctgtg atttcatata ctttgtaaga ttgccttaaa tgtattgcct 82380 tcttggcagc ataatgccag atttttctcc aatatgtcat taaaataatt ttacatataa 82440 caagttgaac tttttaaaga cttatatttt aatctgaatt agcatattta ctaattatat 82500 tacttatttg gcttttcttt agtccgattc tttttttttt tttagtgtac aaacttggca 82560 ttactcttta agaataacaa gtgaactgga aatgagaggg tggtgacatg aagagagaga 82620 gaagaaatac attccttata tctcttccag ctcctgcatg gaatggagga tctgacagtg 82680 gccgttcctg ggtattaaag ccagtgcaaa agatagagcg tccaaaaggc aacttcttcc 82740 ttatttgtga agtcagaaag taaaatttac attgaagtgc taagctacat tattctgaat 82800 attttggcag tcatatttgg gcagatgagt tgctttcctg aaattactca gcaccgtcat 82860 tcatcctgac aaaagctagt ggtacagatg cacctttggg actgaggcca aggtgaaacc 82920 tgcgttttcc aggtctgccc actcagtttt ggaaggactc tcaataaaac cggcctcaca 82980 ccccaagcat cacccctcct gtccttagta agtacactct ggctggaatc tagggtccca 83040 gcatctagcc cttgggactt cacataaatt catcaagtat cttcctccac tcaaaaatct 83100 cttacagaat ctttgacatt ttaagcttca ttactgcaaa gtggatatag ttcattctca 83160 gcttcaggat tccagaagca tacataccag gtcagaatgg agaggcatca cgctttcctt 83220 cagcaagctt caggggagac aggatttagg gtgggctaca catataccag ttgtaggatg 83280 ttttgaacta tattcttgca atcacagaca ggttgtccca gagaaaataa tctggctcta 83340 acttctcttg ttatcagtga aaagcaaaaa ttacttagtg caggtatgct taaaggaaga 83400 aaaaggcaag agaaaagtga gaggtaaaaa ttattaccat tttaattcca tgattctcag 83460 caatgaagga gcatgattga aatcccatgt gcccagtcat atctgtaaat gagagtatga 83520 tttttgaaga ctgtattcaa ttgtttcaac ttgagcaatt gcaagtaaga cttaggactg 83580 tgtttaccag ttactgttat ttactattac tttctaaatg tgacctgact tgaaaccttt 83640 atagatgcaa tttttatcca tcacagaaca agctctaaag aggagagcag cttcaacttt 83700 ttcaagtatt ttttttaaaa ggatttaact ttgaccaaca ccaaacttgc atcttgttaa 83760 ggtaactaat aactgactgc tataacaata tttagaattt tgtttaacag caactgtcaa 83820 aaaaacaagt taaaatagcc caggagatgg atggcgatta actctgcgtt ctttttagac 83880 tgtgttatta attagctctc tagactcaaa taggttacat cctctgagca gtaaattgca 83940 tgccatttgc aagctctgtg gatgaaattt acatgtggcc taaatgctat ccacattgtt 84000 ttgttaagta gcattttatc tctctggact ggtcccttgc ctcctccccc agccccagtg 84060 gaaagtttta ttcacttttc ttgcgggaag ggaaagtcgc atgtagtttg gtcatttggc 84120 gccatcttct tttttattgt taaatccact aaaggcagtc atgcctggca gtaccaggcg 84180 ggctccttcc ggggttctgg tcggctaagc attcagagtt ctttgctttt tatttactag 84240 aaatgttttc agcttctgtc tttgctttaa gatctgatta aaaggaacct taaaaaagga 84300 acatagattt tggtgtatgt ttttcctctc tacttctctt ccctgtgccc cccaaaccca 84360 atcaccaact tcccccatcc ccagcaaaca cgggcttttt tgtgtattta tttaaaagca 84420 ttttaggaag caccgtaata ccgcacagct tggaggttaa gatagaattg gatgtttccc 84480 tcaccatcag ttgatggaat catcagtgtt ccggttctat ttatcttcat gatttgagaa 84540 tgtttctgaa cagctgccct tccgaggatg ctggtattta gacagacctt cctgtcattt 84600 atctgactca caggcacaac tcttttgaaa gaattaatat caaacttaca tatgaaaatc 84660 taccatttag aaatggattc tttttcagta cctacttttc aattcaaccg gggagatccc 84720 atctatttta aaaaatcatt aatcacatac ttctgacatt ttccctttca gtttcctcag 84780 ggggaaaaaa gttatttgaa taacaaacaa acaaacaaaa acccctcatc gcaaatagct 84840 gtcagcctcc tatgtgaaca aaagcgctct ctcacactga gacctaccgt gttttgttta 84900 gttagaggca gcagggtggt agggacacta tgcagaaagg cttgggttaa tgagcacttt 84960 ctggattgag tgtctctcct gattaaccct tggattactt gctttgagtt gctaaccctc 85020 tctcactgcc cactcaagaa tttcccacat ggtagcctca tccatagatg cccttcccta 85080 gatgcactga tggtagacag cataaaaatg tgtaagcact gtagctttcc aatgaactga 85140 aacaaaaagc ttaagcatta ctttttattt ccttgatcta aagaacatgt tttgggggat 85200 attttcttaa tcaatatcta agttatctag agttataaat actataaata aattagttac 85260 aaactaattt ttagacacaa gtcttttgtt caaaccaact cttacataga aactctaaaa 85320 atttgggggg gaaggggaca gttggggatc agaatcactc cccattatct ctctgttggt 85380 gctccccaaa ggatcttcag ggaacgacgt ttaaaaacca ttttgtatca tgaaatggga 85440 cccgaaagac attctttcta gtgactttgt gttagattga gtcatatgaa attgccactg 85500 tgtgacccat tttgacctaa aaaaaaaacc aaaaaacaaa aaacaaaaaa ccagcactag 85560 ggtaccagag tatttttagt gtaatcactg tacgtgataa gaaaatggag aaatgagaaa 85620 gcttgaaact tagactataa gctcctcata agctaatagc gacttcctcc cttcttccgc 85680 agtcacctgg caagtccctt ctatgtgctg ctggttctag ggatacagag ataaaaggcg 85740 tagtcactgc ctccaaatca tcacagtgca aaggacaaat aaatacagaa ggacccatgg 85800 gatgaagaaa cagcccaggg tggtgggaac acagagcgag agtttctagg atcttgaaag 85860 ccatgttgca cggagctccc ggtccctgag ttttcagact gatctttctg tggactgtgc 85920 ctaagtaata acagtttcag aacgtagaaa ctcagtgtac atccttcata gccaggatgg 85980 atatgatagc ctggaagtga acagtaaatc cagtgatttg ttttcttcac tcattctttc 86040 attttaagaa agtgcttaga atccacaagt tgtgcttaat gccagcagac gcattacata 86100 tgccagccct gccccttagt cacaattact ccccacactg acctcccatt gcatttaaaa 86160 attgtcgctt tattgagaca tagttcagct ctcataaagt tcacatttgt tttttttgtt 86220 tttttttttt tgtttgtttt tttgagacag tcttgctcag tcacccaggc tggagtgcag 86280 tggcatgatc tcggctcact gcaagctccg cctcccgggt tcacgccatt ccccggcctc 86340 agcctcccta gtagctgaga ctacaggcac ccgccatcac gcccggttaa tttttttgaa 86400 cttttagtag agacggggtt tcaccatgtt agccaggatg gtcttgatct cctgacctta 86460 tgatccaccc gcctcaccct cccaaagtgc tgggattaca ggtgtgagct accgcctcca 86520 gccataaagt tcacattttt aaaggacaca cgtcagtggt tttcagtctc ttcacaaagt 86580 tgtgtaatga tcatcactat ctaattctag aacattttcc ttaccctaaa agaaacccca 86640 tacccattgg ggttcactcc ctatgcaccc ctcttccttt ctcctgacaa ccactaatct 86700 actttctaaa tctatagatt tgtctgttcg ggacatttcc tataaatggg actatataaa 86760 tatgcccttt tatctctggc ttccttcact ctgcataatg ttttcaaggt ttgtccatgt 86820 tgtagcatgc attagtactt cattcctttt tctggcccag taatgttcaa ttgtaggaat 86880 ataccccatt atccattcca atgatggata ttttttgggg gatatccact ttatggccat 86940 tataatttca ctatgaacat ttgtgtacaa gtttttggtt ggacatacgt tttcattttt 87000 gttgggtata tagctaggag tggaattgct gggtcttatg gtaactatgt ttaacatttt 87060 gaggaactgg gatgtatagc gttttgtgcc tgtgttatga aactaattat gaagcatctt 87120 atattcatta tcattagatc tgtctcctcc attaggtttt aagtttcttg agacagggat 87180 tatccttctt catctttgta tcccccacag tccagcactc accaaggcac aaagtaggtt 87240 cttaggaaac tggtcagaat aaaactgacc aatgcaacat cctccttccc ttaaaatcac 87300 cagcatacct gggaacacag gctttctctt tctctcttcc ctgtagcaag tgacagctta 87360 tcaggaatgg aggcagctcg gtattatcca tcaagccttc cagctgggtg cacaccctcc 87420 ttatctgctg tgggaccttc accagcatcc tgggatttcc tcaggctgcc tcatccccac 87480 aacggcagtg atgtgaccca ctctggttta tgcagatacg ttaagagaga ttattttaag 87540 taccactgaa acccaagcag aggcaaggct ggtggaaacc ccagtatttg ggggcacact 87600 ccctgtttga catggttcag gaatgactca tacatctact ttaaggggga tttggacaag 87660 gaggcactaa gatacctatc caggctttga cttgggagca ttgtgcagga ggtttaagaa 87720 agattatttt aagactatct cagaaggctg gagcagcatc tttctgattt cttctgctac 87780 ctttcactcg gagcctgtga tttctaacat gtatttcagg ttggatttaa gagagagctg 87840 gcccctactg aattggccac ctttgatgtt acagtactga ggaggggagg gacagatgga 87900 acaaaagtcg taattgccca aatttacaat aggttcccag cagcagctcg cacaaaagaa 87960 atgttaatgc aataaactgt aaatggaagg aagctaagca ggatttatgg ctggcgcaaa 88020 cctccatcaa ggcactggaa cctctttcct tcatctgtga ggcatttcag tggtcacagt 88080 agaattgggc tcatttgaaa atcagtggct gctctgtgtc ttccctccct tgtgtgtcct 88140 gcacccccta cacaaaccaa ttcctgtaaa aacctgggga atctgataga acaattggag 88200 aaaaacatca gtcattgagg gtcaagactg caaacccggc agagccaaga gtgcacacac 88260 atttgctgtg cacatgtatg tgttacagct gcaaccaaag cgtgcgtttt ccttccccaa 88320 gtctgtgttg gggacttccg cagacacagc agatggccag agtgtttcca cgtttcagcc 88380 tcgaagtgag agggcagcat gtcattcacc agcctggcac ttacccatcc atcagggcca 88440 cctctataaa tggctgtttt tcacatttgg ttccagcagg ttccatctcc attccggctc 88500 acacatacct ttacctgtgt tgtatcatgt ggggtgctcc ttgtctcctt gtccagattg 88560 ctggcccgct tgcttcatta attaaccgag gagcacgtct aaatggaaaa ttgctttctg 88620 agatctgtgt gtcctggctc catgctgtga ggggctccct gtaattaaac acgttttaag 88680 agttgctgtc ttgcgcatgt gccctggaca tcggtgcttt ccccactggc tgggtagttc 88740 tgtttcagac cttagaccta aatgataata acagttacaa ggaaacttgc atatcagttg 88800 attaagtgtg gggaattttt ttccttttga aagttggggg aaagaactcc tcagtgggga 88860 agtgattttt ctgccctgta gggatgggaa aatggttaat catcatgggg gcctcaacag 88920 acctcagcat gttcgcgaag tccttggcct caggttcctc atccatccca ccgcgagagc 88980 gatacggctt gggtaagccg cgaatcccct cactgggctc caattattcc agaattctaa 89040 ctttaaaaat aaaatattca tatttaaaag ttcctgctac cgtttcaaag aagcttccca 89100 agaagctctt cagagctggg gcatggagga acctgtcact gggtcccttt ctgctggggg 89160 atcagttcct tttataagta ggaaaagatt tctccatacc ccttgcaaag ttcatggctg 89220 acacccctat aacaaaagac aggttaacaa gagcaaagca cacaaatata tttaatacaa 89280 gttttatgtg acacaggagg cttctgaaat gaagcctcaa agacccaggg aaaaccgcgt 89340 ttttatggac agtcaagcag aaatatgatg agagaacaaa agggtttgat gtagcgtaat 89400 aaacttagca agcccgttca gattcttctt ggtgttcctg tgtgacattt tttttttcct 89460 ttttgttttg agacggagtc tccctctgtc gcccaggctg gagtgcagtg gcgtgatctt 89520 ggctcactgc aacctccgcc tcccgagttc aagagattct cctgcctcag cctcccaagt 89580 agctgggatt gcaggtacgc accaccacac ctggctaatt tttgtatttt tagtagagag 89640 agatttcacc atgttggcca ggctggtctc gaactcctga ccttagatga tcccctgcct 89700 tggcctccca aagtgctggg attacaggaa tgagccaccg tccccagtgt gacatttctt 89760 ttctctgggt acagggcagg acacctgtca catgagggtc ttcaggggag gagggagaag 89820 gtcagagggt gaccttccta cttctgcagt tttctcgatt tctttcagtt tacagtactc 89880 agtaggacaa ggtgcatatt tggggatatc gtgttctgag ccccaacagt aacaaagaac 89940 aaagaaagcc tttaggcagt ttttgctgag actctcaaat aggaatttag agtgatggtc 90000 cttgagtcag agaggccact agagaaagtt tgactttcca tgtagaatag caagctctcc 90060 tctggcaagt cttttccaga caaggctcta taattttttg ctaataaatg tgtggacaaa 90120 gttatgggat gtatagaagt ctgacaccaa aaccatgtca gagacttttt tttttttttt 90180 aaaccgagtc ttactctgtt gcctaggctg gagtgcagtg gcatggtcat ggctcactgc 90240 agcctcaacc ttctaggccc aagagttcct cccacctcag cctcctgaat agctgggacc 90300 ataggtatat gccaccacac ccagctaatt tttagttttt ttatagagac agggtctccc 90360 tgtgttgccc aggctggtct caaactcctg ggctccagca atccttccaa agtgcagggt 90420 tatagacata agccactgca cgtgtcctgt aacaaagatt gttagtaaaa gttattgaaa 90480 tttaaatcta tgattcaagt cctgatacat aagacacatg gcacatggta aaaattgatt 90540 tgattacatc ctaggaggcc tagacttggg aaagaaggaa aaaaaaaagt atgaggctgg 90600 gcatggtagc ttgtgcctat aatctcagca ctttgggagg ctaaggcagg gggattgctt 90660 gaggccagga gttcaagacc agcctgggca acatagcaag accccatctc taccaaaaca 90720 aaacaaaaca aaacaaccac aaaaaaaacc cacacaaatt aaatttaaaa agaaaaagat 90780 gaaaagaaag atgagaagat aaggaaatat ctgtagacag tttaagtctc tatttttttc 90840 tacaaatgta cagttatgta ttgtaacata ctgcatcttt tgaccctgtc ttctctgttt 90900 caacagagct tatctttttc tatgtatttc tgctgctact gcttttccaa accacagcca 90960 ttgtcctgta atgcccttat gcatttggcc aagccctctt agcttcttta ttattgtggg 91020 gtcttagttg atatttgggg tgtatgacat tacaaaacac atgggatgta gatgtggatt 91080 gggagagccc ctgaattgta gcactctgct ttcctcatct gtaaaatggg tataatcaaa 91140 gtcttggaag ggtaattgta aaggggtgtg cagacagtgg ggttactgtt atttgcaagg 91200 atccgcccat agttttatct gcaaatgtca ctagcttttg atttactcac tctcgcttgc 91260 gtcttctttc gtgctgatgt tggctctgct ttatcccaca ggctttttat tattattatt 91320 acttttgaga caaggtcgct gtctgtcacc caggctggag tgcagtggtg caatcttggc 91380 tcactgcaac ctctgcctcc caggttcaag tgattctccc cactcagtag ctgggattac 91440 aggcacgtgc caccacaccc agctaatttt tgtatttttt tggtagagat ggggtttcac 91500 catgttggcc aggctgagtg atcctcccgc cttggcttcc caaagtgctg ggattacagg 91560 catgagcccc tgcacccagc ctttctttct ttcttttttt ttttttttga gacagggtct 91620 cactgtgttg tgcagtggct cgatcttggc tcactgcaac ctccgcctcc tgggttcaag 91680 cagatctcat gtctcagcct ctcgagcagc tgggagtaca ggcacccgcc accacaccca 91740 gctaattttt atattttttg gtagagatgg ggtttcacca tgttggccag gctggtctcg 91800 aactcctgac ctcaagtgat tcatttgtct cagtctccca aagtgctggg atttcaggcg 91860 tgagccaccc caccgggcct cccaacaggc ttttaaagca ccagggcagc agggcactgg 91920 gccaacaggt atatttggga atgtgcattt ggtttcatgt gtaataggaa agagattaat 91980 taaggttgtt agtgtggcct aatactaaat ttcaggaagc ctcacaggac acatgaaaca 92040 aatctttaca acacatatgt gttttcatgc tgctgaacat tttgaagacg ttttgccatg 92100 ctggagtttg tttgttttgt ttgtgttttt gtttgaggtg ccgtcttatt ctgtctctca 92160 ggctggagtg cagagttcag tggcacaatc ttggctcact gcaacctcca cctcccaggt 92220 tcaagctatt cttctgcctc agcctcccga gtagtgcctg gctgctgttt ttttttttta 92280 attgttaaat tagatgggct cagtattacc gtgccttgat ggagtttcta gttgagggat 92340 cagtgtcatt tctgggtccc catcagaatt acgttcaagc tataagtagt tatgcaaagt 92400 cgtaggttaa atgatttggg aataaaatgt catttgacgt gacagaaatg aacccttgga 92460 ggcccacatt tccactggga cttgctctca gttccagttc tcatgttaag taattttatt 92520 aactgaggca aggaggggca tgcggtgaca agggaaatat tttttgctaa cattttaatc 92580 ctaatcacaa aatttattgt gtgtggcttt atatgcattt gtagctataa agccctggaa 92640 gatgatgaaa gtaaaaatta gaatgtgtgg tttttctgcc caggtgttat ttaaagcatt 92700 gtatgaattg tcaaaaagat taattgttgt tgcttgcagc taaacagatg ataaatttta 92760 aaattatatt attactgtgt gtcagcataa aagctctgtg tcccaagtgt gtcacctttt 92820 tctgttgctg ttgacaaggt tcacatttta tagcacaccg ccagaaggtg ttgacatata 92880 ttcagattac tgattaaatg tttttaaaac gtgccactca gaaactaaca ctgatgttct 92940 atgaaagagt catttttcgg agtaagattt tttttttccc ttcatcatta acatggagga 93000 aatgttaaac actgacattt taaaaaatga acctgggact ggcgcagtgg ctcatgcctg 93060 taatcccagc accttaggag gccgaggtga gcggatcacc tgaggtcggg agttcgagac 93120 cagcctgacc aacatggaga aaccccgtct ctattaaaaa tacaaaatta gctgggtgtg 93180 gtggtgggca cctgtaatcc cagctactcg agaggctgag gcaggagact ccctcgaacc 93240 cgggaggtgg aggttgtggt aagctgagat cgtgccattg cactccagcc tgggcaataa 93300 gagcgaaact ccggtctcta aataaataaa taaataaaaa cgtggctggg cgtggtggct 93360 cacgcctgta atctcagcac tttgggaggc tgaggcaggc agatcacgag gtcaggagtt 93420 cgagaccaac ctggccaata tggcgaaacc ccatctttac gaaaaatacc aaaaattagg 93480 tgggcatggt ggcacgcgcc tgtaatccca gctactcaga aggctgaggc aggaaaattg 93540 cttgaacccg ggaggcggag gttgcagtga gccgagatcg cgccaccgta ctccagcctg 93600 ggtgacagac caagactccg tctcaaaaaa aaaaataaaa ataggccagg cgcagtggct 93660 cacgcctgta atcccagcac tttgggaggc caaggtgggc agatcacaag gtcaggagtt 93720 cgagaccatc ctggctaaca aggtgaaacc ccgtctctac taaaaataca aaaaaattag 93780 ctgggcgtgg tggcgggtgc ctgtagtccc agctactcga ggctgaggca ggagaatggc 93840 gtgaaccacg gaggcggagc ttgcagtgag ccgagattgc accactgcac tccagcctgg 93900 gcgacagagc gagactccat ctaaaaaagt aaaataaaat aaaatgaaaa taataaataa 93960 ataaataaac ctaatgttac tgcactttcc catttcaaat tgcagccagc aatgaaaaca 94020 ggcattagca ttcccatttc ttctcttctc cttcactgga agggcaacaa caaacacacc 94080 cacggtgtaa aaacagcacc aaggccgggt gcagtggctc acacctgtaa tctcagcact 94140 ttgggaggcc gaggcatgcg gatcacctga ggtcgggagt tcgagactag cctgaccaac 94200 atggagaaac cccatctcta cttaaaatta ggcgagcatg gtggcgcgcg cctatgatcc 94260 cagctactca ggaggctgag gcaggagaat cacttgaacc tggaggcgga ggttgcggtg 94320 agcggagatc gcaccattgc actccagcct gggcaacaag agaaaaactc catctcaaaa 94380 caaaacaaaa caaaacaaca gcaccaagga aggcgctaaa tggctacttg taaacaaccc 94440 aggttggaca ctggacccac gacaaggagg caagttccgt cctgtggtgg tgtttgtgat 94500 gggaagtctg gggctttgac tccctcaagt ttccaggcta acacacacaa ctcttcccag 94560 cagctgaggg gccccgaagc cttgatgtcc ctttcacgtt gaaggacctc actggtcttg 94620 gctgtttgcg ttttgtggat ggagtgggcc agtcttcaga gaactcaaat gtgtatttgc 94680 tgcagggagt gataagtaaa cataatgcct caagaatcaa catttgaatg cttttctttt 94740 tggcgttaag gtataatggg acactggcaa tatatgctgt ctctctgaac acagcatgaa 94800 agaacttgaa aacaaatgat ttagtattca ttacggaaaa gttggatttt tttccctctc 94860 tgattgtcaa gatttcttcg tcgatgtcag ttttccagtg tgaatttttc ctctccactc 94920 agaggaagtt gacgttggtt cagtgatgtt acagaggatg ctgtaagaca gccaggagcc 94980 caggccggtt gtcacttcat cccagcatgg tgcaaagtta gagatgttgc agtgacagcc 95040 ttgggtgccc tcaggggcaa ccaagtctct aaataatctc tgtgaccaaa agtacatagg 95100 aggttgtaaa tatcccacaa caaaaataaa gatagctgcc atttcccaga acttaatgca 95160 tatcaggaaa tgttacctct ttatatatat tgtctcattt aaatccagta agatagcagc 95220 agctgtggga ggatgtggtt tttgtttttg tttttgtttt gagacagagt cttgctctgt 95280 cacccaggct ggagtgcagt ggcgggatct cggctcactg caagctccgc ctcccgggtt 95340 cacactgttc tcctgcctca gcctcccaaa gtagctggga ctacaggcgc ctgccaccac 95400 gcctggctaa tttttttgta tttttaatag agacggggtt tcacatgtta gccaggatgg 95460 tctcgatctc ctgacctcgt gatctgcctg cctcggcctc ccaaagtgct gggattacag 95520 gcgtgagcca ccgcgcccgg cctgaggatg tggttttatt cccatttaac aaaggcttga 95580 gtatcacttc ttatttattt atttatttta ttattattat ttttgagacg aagtctcact 95640 ctgtcaccca ctctggagag caggggtgtg atctcagctc actgcaacct ctgcctccca 95700 agttctagtg attctcctgc ctcagcttcc cgaatagctg ggagtacagg tgtgcaccac 95760 cttgcacggc taatttttgt attagtagag atggggattc accatgttgg ccaggctggt 95820 ctcaaactcc tgacctcagg tgatctgccc atcttggcct cccaaagtgc tgaggttaca 95880 tactttatta acaaaggagt gaagtgatac cccctctccc ctgtaagtag cagccaacat 95940 tcaaacccag gtgtgtcaga ttttagagcc acactgacat tcagcagcta ctgactgatt 96000 gtctactatg tgttaggcat tgttttcatc acacctttta ttttttgttt tgttttttag 96060 ggacagagtt ttgctttgtg gcccaggtgt agtgcagtgg catgatgttt gctcactgca 96120 gcctcgagct cctggcctca agtgatcctc ctgttttggc ctcccaaaat gctaaggtgc 96180 tgggatcaca ggtatgcgcc actccgctca gcccacatat ttttaagtct gctttttaac 96240 ctaatttact tattttgggg gtcttaaaaa attggctcac agccgggcgc ggtggctcat 96300 gcctgtaatc ccagcacttt gggaggccaa ggcgggtgga tcacgtgagg ccaggagttc 96360 aagaccagcc tgatcaacat ggtgaaaccc tgtctctact aaaaaataca aaaattagcc 96420 gggcgtggtg tcgcatgcct gtaatccgag ctacttagga ggctgaggca ggagagtcgc 96480 ttgaacctgg gaggcggagg ttgcagtgag ctgagatcac accatggcac tccagcctgg 96540 gcaacaagag tgaaattccg tctcaaaaaa aaaaaaaaaa aacctattta aaaatgaagg 96600 ctcatgcaga atgctctgca agttcaaaat aaaacagagc tctgagcgcc tagaggcttt 96660 ttgccttaag gggcgaggag gaaaaagatt aagatgctcc ttggaaaata gccctttttg 96720 gctccatctc ctttactgtg gtcacctgca catgccttta gttcttctgg atttatatct 96780 aagcacgttg ctctgctaca taagaagctg acaacatcag ttaccttcct ggaggtgaag 96840 gagagacaaa ggggctgagt gggtgagagg aatactttcc accatgaact ctttggtacc 96900 tttcggaacc acgtgaatac agtatctttt caaaagaaaa gggtgctata ttcattgtcc 96960 tagactatta agcactttaa aaggcacttc aggtaatcta gttgaagtgc aaatttcact 97020 gaacccagac tattatgcaa acaggactag ctctgtattt attcttttat gttgtggctt 97080 gccatccaat ttgtgtttcc ggggctgggc acgaggtggc tctagcctgt aatccccgca 97140 gtttgggagg ccaaagcagg cgatcagttg gggccaccat ctccattgtc cctttttaaa 97200 tttaagtgac catagcttct tagtatgata tcaggttttt gttttcttcc caccttgtct 97260 ttgtttttta gtgtgtggat gcctttgaaa ttagtttttt tgtttgcttg gttttttttt 97320 gagatggagt ctcactctgt cgccaggctg gagtgcagtg gcgcgatctc ggctcactgc 97380 aacctctgcc tgccaggttc aagcgattct cctgcctcag cctcccaagt agctgggact 97440 ataggcacat gccaccatgc ccagctaatt ttttgtattt ttagtagaga cggtatttca 97500 ccgtgttagc cagagtagtc cgatctcctg acctcgtgat ccgcccacct tggcctccca 97560 tagcactggg attacacata tgagccactg tgcctggcca aaattagttc attttttata 97620 catgtccttt acacaggaga tgtattcaga aagattatct atattttttc ctttaaacaa 97680 tgcatttgtt tgtttgtttt atttgtaagc tcatctcctg ggtttagagc agaatgaaaa 97740 atttgacctt aatcttctct tatccactgg ttggaagctc ctacttttat gtcaacagac 97800 ataaaaaagc ttatacatat aagataatgt atagcatgca taaagattta tagaatgcta 97860 tgtctcataa atttcacagt tataaaacaa aacctaagct tatgcatgtg gagatattcc 97920 tgtgtttgca gttgtcagtg acttctagag aatgtggtaa aggaaaaaag cacctgtgga 97980 agttatttat gtaaaagttg cttatgtaaa gactcaagcc attaacaaga gaaggagact 98040 tctttatatt gttaatgaca ttcagatctt tcttctgaat gagggttgtc actctgaatg 98100 agtgttgtca ttcatttcct ccaagccttc agatatcttt ttcctttatc tgacacattt 98160 caggaaagag taagggaaag atttatttat attactttga tggtttcatt ttctttgtgg 98220 aagtccagtg acccagatat agagatcttc ttggaatata ttactttgat ggttactttc 98280 tctttttgga agtccagtga cccagttata cggatgtcct cagaacattt gaagtctagt 98340 tctgcattat aaaatagccc agttgccata ggttgatttc ctgtaaacct aaatcatgat 98400 tgcaaactaa tttggatgct aattaggact catataatga ttatatcaat ttataacttg 98460 tctaacaaca atgcatttct ttctttgcta ggttaagtat ttacactatg acctgtgaac 98520 agggaaaccg gcctgtgttg agtactttct atgagccagg tgctcgactg tgtacaaact 98580 tagaagaacc aggtgcacac gccaggtttg ggggccgttt gacagtcagc attcaataaa 98640 tgtgttgttt aagttgatat aattaattta aaaggaagta gcaggtgatg gtagtacact 98700 tcattgtcct agaatattaa atactttgtt gtcagcagac ggacttcttt catatgcaca 98760 ggtcatcttg agcacggatc ctaagcctag tctttaatcc ttcctagcat cctacatgag 98820 ccaaacttag acaaaaaaca aggcaactct tggttatcta gggcaatttg aaatctcagc 98880 tacctccact gtgtccagct caccgcagtt atgcatctat ttacaacatt atgtttgcaa 98940 cattatgttt aagcaaacca caatgaaagc attaaacata gaataactat gatccagcaa 99000 ttttacttcc aagcatatac cgaaaagtgt tcaaagcagg gactcagata ctgtgttcct 99060 gggtacatgg gtacacccat gtttatagca gcattattct tgatagccaa aagatggaag 99120 caacccaggt gtccatcgac aggtgaatgg gtaactacaa tgtggtgtac acatgcacac 99180 acacacacac acgcaagaat attattcaac cttaagaaag aatgaaattc taccagtcac 99240 ggtggctcac atctgtaatc ccagcacttt gggaggctac ggtgggcgga tcacctgagg 99300 tcaggagttt aagaccatcc tgaccaacat ggtgaaaccc tgtctctact aaaagtatga 99360 aattagccag gtgtggtggc acatgcctgt catcccagct acttgggagg ctgaggcagg 99420 agaatcgctt ggacctggaa ggtggaggtt gcagtgagcc aagattgtgc ctttgtactc 99480 catcctggag agcaaaattc catctcaaaa aaaaaaagca tgaaattctg atacctgcta 99540 taacacagat gaaccttgaa gatatgctga gtgaaataag ccatatgcaa aaggacaaat 99600 atgtgattgt acttatatga ggtacctaga gtagtcaaat tcacagcaca gaaatgcgaa 99660 tggtggttac ccggggctgg ggggaaggag ggaatgggga attggtgtta gtgggcttac 99720 agtttcagta gggggtgatg gaaaagttct agagatacat agtggtaatg gatgcacaat 99780 attgtgaaag gacaaaacta tacctaaaaa tggttcaaat gctaaattgt atgttatgta 99840 tattttgccc caattttttt ttttgttttt ttttgtttta aagacagagt tttcctcttg 99900 ctgcccaggc tggagtgcaa tggcatgatc tcggctcact gcaacctccg cctcctgggc 99960 tcaagcaatt ctcctgcctc agccttccaa gtagctggga ttacaggctc gtgccgtcat 100020 gccccgccaa tttttgtatt tttagtagag acagggtttc accatcttgg ccaggctggt 100080 tttgaactcc taacctcgtg atccacccac tttggcctcc caaagtgctg gcattacagg 100140 cgtgagctac cgtgcctgac gtattttgcc ccaattttta aaagcaacat aataaagaca 100200 aagccactgg gaaggatata aaatgcccct gagccaaaca ctgtatagcc aaaagagcaa 100260 aactacaaaa actgcaccaa gcttctttgt aaattcattc ttccaccctc caggacactc 100320 ttgcctggtt tgcatcctga gagtctcctg gggttccagt tatttcaagg tcacagtcag 100380 gtaggcacgg tggctgtgct atggtggaaa tggcttttgg attcctcgta attttggatt 100440 atcggtgccc tgtttttctg agaccaaaac ttatcaatag agtattacgg aaggtgatat 100500 gtagtaagtg cacctttctt gggcattcag tctaaattca atagtaaagg gaaaatcaca 100560 tatagtcaag tccaaattgc tcatgatgtt acagtagatc tacatgtccc taacttgatt 100620 acctattttc cctccagcac tggagtgcat ctctgcttct tcagccgagc tccagaagga 100680 gaagatggct gcatttagag tcagactgga ggaaaaggag cattttgata ttttatttta 100740 tttttattta ttttttagag acaggttctt gtgttgtcat ccagactgga atgtagtggt 100800 tgcagctcac tgcagccttg acctcctggg ctgaagccat cctcaagcct cagcctcctg 100860 agtagccagg actacaggtg ccgtgccacc aagcccagcg aatttttgta tttttttgta 100920 gagacggatc ctgctgtgtt gtccaggctt gaaatttgat tttaaacata ttaggcatca 100980 cactaagccc ccaagacaag atagaagctt acagaacctt gactatctgg aatgactttc 101040 acagagtgat ttcatctttc ttcttaccct caatgagtaa cgtgaaggct gagcaggtca 101100 tactgttcaa attatttatc ttctttagac ttttttcttc caaacaccag tagttgaatt 101160 tgagtacttt aagtgctagt attatgcaat ttcattttat tttattttat tttatttttg 101220 agacagagtc ttactctgtt gcccagactg gagtgtagtg gtgcgatctc ggctcactgc 101280 aacctccgcc tcccgggttc aagcaattct cctgcctcag cctcccaggt agctgtgttt 101340 acagtcatgc gccaccacgc ccggctaatt tttttgtgtg tctttagtag agacgggatt 101400 tcaccgtgtt ggccaggctg atctcgaact cctgacctcg tgatctgccc ccctcggcct 101460 cccaaagtgc tgggattaca ggcttgagcc attgcaccca gcctggatta atgatttcga 101520 atgaacattt acaatgatat gttttataat aaaacacatt aaaaagtttg aaacactagt 101580 tactagaaac agttctctct gtaatgacag ttagtcatgt tgttgctgca gtgacagttg 101640 acttggtgtg agggtattga taaagcctgg tgatttgtac acttgcccat attatgcttt 101700 tcccaggcta gctatgcaaa tctcatttcc cttacatttg aaagtcattt cagaattgtt 101760 tcattagggt tgaggcaagc acaaatcatg aatgcctgtg tcttctacca ccaaacagat 101820 tctgttggac ccacaactga tatgctttca gccaggttcc atttagcatt caccctggac 101880 ttagggactc tacaagagtg ctgggtattt agttttgttt tgttttgctt tttgagacag 101940 agtcttgctc tgtcacccag gctggattga agtggcgcaa tctcagctca ctgcaacttc 102000 caccccctgg gttcattctc ctgcctcagc ctcccaagta gcagggatta caggtgccca 102060 ctaccacacc cggctaattt ttttgtattt ttggtaaaga ctgggtttca ccatgttggc 102120 caggctggtc ttgaactcct gacctcaggt gatccacccg ccttggcctc ccaaagtgct 102180 aggattacag gcgtgagccc tcacacccgg cctgatgctg ggtgttttgt acagtggtcc 102240 caccttactg tgtagaaatt ctcagtcatc cacctaattt gtttatttcc cattcatata 102300 cttcatttat tcactcactc acttggccat ttatgcatat ttattgattt tgttaaaaag 102360 atacctgaat gagtggaaca ctgagatgat atagtggaat ggacggatag tggttagccc 102420 cttggaccca tgagggccag gttctgaaat tccagctctg aaattctacc agctggttga 102480 ccttgggcaa attacttagc ttctctgtgc ctcatttctt catttataaa atggagataa 102540 taggttaaga gggttagatg agacattcat tcatagtact tggcacacag taagagccca 102600 gtaaatacta gctgttgtta tggattgaat tgtgttgcct ccccacaaac tcatatgttg 102660 aagtcctaac cacaggtact cagaatgtga ttgtatttgg aaacatggcc attgtagatg 102720 taattattta agaagagtga ttaggctggg catggtggct cacacctgta atcccaacaa 102780 ctttgggagc ctgaggtggg cggatgatga gggcaggagt tcgagatcag cctggccaat 102840 atggtgaaac cctgtctcta ctaaaaatac aaaaattagc cgggcgtggt ggcaggcacc 102900 tgtagtccca gctactcggg aggctgaggc aggagaactg cttgaaccag gggggcggag 102960 gttccagtga accgagataa cgccactgca ctccagcctg ggcggcagag cgagactctg 103020 tctaaaaaaa aagaaagaaa aaaaaggagt gattaggttg ggcactaatc caatatgatt 103080 gctgtcctta aaaaaagaga aaatttgggc acagagatag acatgcatag agggacaatg 103140 gccatccaca agccaaggag agggtcctgg aacaaatcct ttcttaccag tcctcagaag 103200 gagccagccc tgctgacacc tcagtttcag acttccagcc tccacagctg tgagacaata 103260 aatgtctgtc agtgaagcca ctcagtctgt ggttctctgt cacagcagcc ctggccgaag 103320 acacagctgg cagcaccgtc ctccgctact gtgtttctca ttgacccgag aacctgcctt 103380 tgtccatgtc ctggccaatg ggagatacat tttctccttc tcagcttgta ttcctgtcct 103440 tttctttctt tttttacaaa atagcataca aaaaagttcc tagcaagaag aggtgctcca 103500 gaagttccct ggctgtttca ttcctgtgtc tcttcctaaa aagctgcagt tgaaaagata 103560 gaatttgttt tctcttagca cattcttctc actttctaag cttgattttt ctttctttga 103620 aagagtgtaa ccccttcaaa attaactcct agagattgct cacctccctc ccaaactttc 103680 gatgaggagc gtttattttg tagactctta tgtgtgaatt ctttcaataa ataggggatg 103740 cagagaagca gctttgtgga gtgaagcagt aggaaagagc ctgttgggga gagagcttcg 103800 ccactgcatt tcagtagctg gtttcgcccc tacctttttt ttttttcttt ctttcttttt 103860 tttttttttt tttgagacgg agtctcgctc tgtcgcccag tctggagtgc agtggcgcta 103920 tctgggctca ctgcaagctc cgcctcccag gttcacgcca ttctcctgcc tcagcctctc 103980 cgagtagctg gggctacagg cgcccgccac caagcccggc taattttttg tattttcagt 104040 agagatgggg tttcaccgtg gtctcgatct gctgacctcg tgatctgccc gcctcggcct 104100 cccaaagtgc tgggattaca agcgtgagcc accgtgcccg gcccaccctt acctattttt 104160 aaatggtgac ttgtgttttt atttgtttgt ttttaaagac acttgaaatt ggacagtgtt 104220 tctccatcct ctccagaggc ccagagcaat gtcgcaagga tgcattctgg acgaggcagt 104280 cacggggccg cacatggcat ttgttcttct cagggaccgt ctgctgtgtt tctctgcccc 104340 agtggagctg ggggaataat aaagctctta ttatttatac tgcacagcat ttttttcagt 104400 ggtccttgtc attgagactt atgaagacaa tgtaggacaa gagggaactt gtgagttttt 104460 atgcaggtag ggaagaaaag taaaaggggc tatatttcca gggatattgc tttttcccaa 104520 acccctgcac ttccccagtc cttttcttta tcttcctttc ccaaatgaga ggtgtccttc 104580 ttctccggta tcagccccct agtttcttcc ctgtcctcgg ggaatcttgg tacaccattt 104640 agcccctgtc ttggtttttg actctgtccc tttgtggaat tcttacccat agcttacagt 104700 gatgtttcac atacatctct gccaaagatg aagtggaaaa taacctttgc tttgtaagca 104760 catctccttc aagctatcga caagtctcct ggcttctctt agtttctaac cccttttttt 104820 tttttttttt ttttttgaga cagagttttg ctgttgttgc ccaggatgga gtgcagtggc 104880 gtgatctcgg ctcactgcaa cctccgtctc ctaggttcaa gtgattatca tgcctcagcc 104940 tcctgagtag ctgggattac aggcgtctgc caccacaccc agctgatttt tgtactttta 105000 gtagagaggg gttttgccag gctagtcttg agctcctggc ctcaagtgat ctgactgcct 105060 tggcctccca aagtgccagg attacaggtg tgagccactg ctcacagtta tctatttgtc 105120 ttagtccatt taggctgcta taacaaaata ccataaactg ggtgtcttat aagcaacaga 105180 aatttatttc ccacacttct ggagacttgg aggtccaaga tcaggcagtg gcaggttcag 105240 tgtctggtgc taaggaagca cctgcgcctc ccggtccaca gacgcacacc ttctcactgc 105300 gtcctcatat gacagaaggg gtgagggagt ccgtcttttt tttttttttt ttttttttga 105360 gacggagttt cgctctcgtt gcccaggcta gagtgcaatg gcgcaatctc ggcacgcaac 105420 ctccacttcc cgggttcaag cgattctcct gcctcagcct cccaagtagc tgggattaca 105480 ggcatgcacc accacgcccg gctaattttg tatttttagt agagatggcg tttctccatg 105540 ttggtcaggc tggtcttgaa ctcccgacct caggtgatct gcccacctca gcctcccaaa 105600 gtgctgggat tacaggcgtg agccaccgca cgcagctttt tttatttttt attttttaat 105660 atttttgaga cagagtcttg ctgtgtcacc aggctggagt ccagtggtgc catcttggct 105720 cacggcaacc ttcacctcct gggttcaagc gattctcctg cctcagcctc cagagtagct 105780 gggattacag gcgcccacca tcacgcccgg ctaatttttt gtatttttag tagagacagg 105840 atttcaccat cttggccagg ctggtctaga actcctgacc tcgtgatcca cccgccttgg 105900 cctcccaaag tgctgggatt acaggcgtga gggagtctgt cttttataaa ggtgctgatt 105960 tcatttatga gagctcagtc ctcgtgacta atcaccaacc aaaggcctca cctccacatt 106020 tgatcacact gggaatgaag acttcaacat actttgcagg ggacagaaac attctgtcta 106080 tagtaccatt aactttctgc tatggaagtt gaagacagtt ctcttttgtc gtattatacc 106140 cctgatacac acttcagtgt ttatactgtg ccaaggaaag cagtgttcac agctgagcca 106200 tacggtacac tacaattttc ctttctcata taactttttg tccccttgga gttagcaatt 106260 gacttttttt tttttttttt ttttgagaca gggtctcgct ctatagcgca ggctagaatg 106320 cagtggcgtg atctcggttc actgtgacct ctgcctcctg ggctcaagcg atcctcccgc 106380 ctcagcctcc caagtagctg ggaatacagg tgcgtgccac catacccagc taatttttgt 106440 ttttttgagt tttttttttg gtagagacag agttttgcca cattgcccag gttggtctcc 106500 aagtctggag ctcaagaatc tccctgcctt ggcctccaaa agtgctggga ttacaagtgt 106560 gagctaccac acctggccag tgattgactc ttttgctaaa actaattttt tcttccaact 106620 ctttgacaaa gtcgtcaata ttaagcaata tacccttact acttttgatt ttgtttttaa 106680 aggaattcct tctggagtct tctatcctga acttgtcgct ttctaggcca gctgcatttc 106740 tgtgtttcta aaacttccat tgtttataaa acaccataat cctggcgttt gctctgtttg 106800 tactctgtat ttccagtatc tggaaaccat gtcttctttc ttggcttatt tcctcattca 106860 gggctgtgtg tcttctagta gttatgtgaa aagagggttc gtgaaagtta aatgtttttg 106920 aggctatatg tctgaagagg tctttggtgt tcttcagact tcatggaaaa cattttccct 106980 aagaatgtta aaggcattgc tccctttttt gcttctaatg ctgccattgc tttaaaatgg 107040 tgccattttg attcttgatc ctttttctgt aaattttttt ctctcttgaa aatctctttc 107100 ttgaagatct ctcttgaaga tctctttctc cctagtcctc tcaaactttg cattgatgta 107160 ctttgatggg atcatttttg ttaattatgt aggtgttcca taggcctttc agtctgaaaa 107220 tttatgtgtt ttagttctag gagctttctt tgtatttctc tatttctttt tttttttttt 107280 ttttttttta agacagagtc ttggtctgtc gcccaggctg gagtgcagtg gtgtgatctt 107340 ggctcactgc aacctccgcc tcccaggtcc aggtgattct cctgcctcag cctcctgagt 107400 agctgggatt acaggcatct gccaccatgc ctggctaatt tttgtatttc tagtagagac 107460 ggggtttcac catgttagct gggctgatct tgaactcctg gcctcaggtg atccgccctc 107520 cttggccttc caaagtgctg ggattacagg catgagccac catgtctggc ctcaaatttt 107580 tatttttgat agctttttca tgttctctaa tgtttctgat tgattgattg attgagaaag 107640 ggtcttgctc tgttgcccag gctggagtgc agtggtgcaa tcatggctca ttgcagcctc 107700 aacctcctgg gctcaaatga tcctcctgcc tcagcctccc aagtagctgg gactacaggc 107760 acaagacagt atacctggct aatttttaaa tatatttttt tgtagagaca gggtttcgct 107820 atgtgcccag gttggtctca aactcctggg ctcaagcaat ttgctttcag cttcctaaaa 107880 tgctaggatt acaggtgtga gtacatggca cctggccgtg tttgtttgtt tgtttttgag 107940 acagggtctt gctctgtcac ccaggctgga gtgcagtggt acaatctcgg ctcattgcag 108000 ccttgacctc ctgggctcaa gcaatcctct acctcagcct accatgtttc ttttataaat 108060 gatattttat tcctgttttt gcatgtatta taatatctta tttctctgtt tgttctgttt 108120 tttgctctgt tctgctcttt gcattgtccg tttctcttga gtgctcttcc tggttgtttg 108180 tttcggtttt tatctttcaa gttgataact tttgtcgaag gtctggtggt gtttgactgt 108240 cagtccatat ttaaaaatga ggaactggcc tggtgtggtg gctcacgcct gtaatcccag 108300 cactttggga ggccgaggtg ggcggatcac ctgaggtcag ctgtttgaga ccagcctggc 108360 caacatggtg aaaccccatc tctactaaaa atacaaaaat tagcttggtg tggtggcaca 108420 cgcctgtaat cccagctact caggaggctg aggcaggaga actgcttgaa ccggggaggt 108480 agaggttgca gtgagtggag actgcgccac tgcacttcct cctgggtgac agagtgagac 108540 tccgtctcaa aaataaataa ataaataaat aataaaaata aaaatgagga acttaaggac 108600 caggagcagt ggctcctgcc tctaatccca gcactttggg aggccgaggt gggcggatca 108660 cttgaggtca ggagttcgag accagcctgg ccaaaatggt gaaaccgcgt ctctactaaa 108720 aacacaaaaa attagccagg catggtggcg ggtgcctgta atctcagcta cttgggaggc 108780 tgaggcacaa gaatcacttg agcccaggag gcagaggttg cagtgagccg agatcatacc 108840 actatactct agcctgggca acagagcgag actctgtctc taaataaata aataaataaa 108900 taaaaaggag gaacgtaacc atcaatagag agttatttgt gtatggaact gatgggcctc 108960 actgtaaggt tatcagctgg gggcccacca gcttcaccag aggatcacca catatcagtg 109020 tctgtaggct tgttctcctg ggctcttctg tttttcagag aggtatcctg tgctctccag 109080 cttcggggga ttagacctgg cttccagcat tctagaagcc aaggctagga ggcaactggg 109140 gaattctcat tattccatac ctggactttc actcagcccg tttcagcttt tgactaactc 109200 ctccccttca ctgtgttttg cctccacaaa gtgaaagctt tttggggttc catttctcca 109260 gggatttact tcctttgccc ttttggaatg ggacaggtta aggtctaagt gctctttata 109320 gagattttct ttttttcttt ttcttttctt tttttttttt ttgagacagt ctcactcgga 109380 ctggagtgca gtggtgtgat ctcaactcac tgcagcctgg acctctaggg ctcaggtgat 109440 cctcctgcct tagcctccca agtagctggg actacaggtg catgccacca tgcctgggta 109500 attttttgta ttttttatag agctcaagga atccacccgc cttggcctcc caaagtgctg 109560 ggattacagg tatgaatcac tacacccggc ctgtacggat tttcaaacaa tccttttgtt 109620 ccaacccact accctgcctt cagagatacc aggaacctct agttcctaag ctgttccaga 109680 gtcctgtggt agaaataagc ttgatgcttt tggcttgtca tgtttctcag gtcccggggc 109740 tgcaggaagt tagtagtcag tgttttcact tgttgattca ctctccattt gccagtggtt 109800 tgttaacatc tcttataagg gattgattct tctgttatat ctgtttctgt ggatttatac 109860 tcctcccctc ttcattgtgg gttttagaaa gaaagcggag acaaatacta ataataatct 109920 gccatgttat ttagcaaact ttttaaacat ttttaaatta tgaatgagta ttgaatttta 109980 tcaaatgctt tttctccatc tcttgagatg ttcaaaaggc ttttcttttc tcatctgtta 110040 atgaagtgaa caataataaa gtgttttgta atgttaaatt gtccttgctt tattggtgta 110100 attttttttt tttttttttt tttttttttt ttttttttta gagacaaggt ctcgctatgt 110160 tgctcaggct gggctcaagt gattctcctg cctcagcctc ccgaatagct gaaatactgg 110220 tgtgcgccac catgcccggc agacgtcatt tttcagtttg ctgaaattct gaattttata 110280 gaaatgtaaa attgagactg gcctatattt ttctttcttt tcttttcttt tttttttttt 110340 taatagagtc tgtcgcccag actggagtgc aatggcgcaa tctcggctca ctgcaacctc 110400 cgcctcccgg gtccaaatga ttctcctgcc taagcctccc aagtagctgg gataacaggc 110460 atctgccacc atgcctgggt aatttttata tttttaatag agacagggtt tcaccatgtt 110520 ggtcaggctg gtctcaaact cctgacctca ggtgatccac ccacctcggc ctcccaaagt 110580 gctgggatta caggcgtgag ccaccacgcc cagcctatac ttgtttttgc ctccttcagt 110640 ttttatgctt ttttcagaaa tgaattggga aaaaattatg tgggaaactt tccctcttac 110700 tttaatttct tttcttttct tttttttttt tttttttttt gagacggagt ttagctcttg 110760 ttgcccaggc tggagtgcaa tggcacgatc ttggctcacc gcaacctctg cctcccaggt 110820 tcaagcgatt ctcctgcctc agcctcccaa gtagctggga ttacaggcat gtgccaccac 110880 gtccagctaa ttttgtattt ttagtagaga cggggtttct ccatgttggt caggctggtc 110940 tcaaactcct gacctcaggt aatccgccca ccttggcctc gcaaagagct gggattacag 111000 gcgtgagcca ccacgcccag cccccctctt taatttcttg aaccgcttgt ataagatatg 111060 aattatctgt ttcttgggct ggcatggtgg cttacgcctg taatcccagc actttgggag 111120 gctgaagcag gtggatcacc tgaggttagg agttcaaaac cagcctggac aacatggtga 111180 aaccccgtct ctactaaaaa ttcaaaaatt agctgggtgt ggtggtgcac acatgcaatt 111240 ccagctactc gggaggctga ggcaggagaa ttgctagaac ccaggaggca gaagttgcag 111300 tgagctgaga tcatgccgtt gcactccagc ctgggcgaca gagtgagact ctatctcaaa 111360 aaaattagaa aaaaaaaaaa aaaaaaaaag aattattttt tatttttttg aggcagggtc 111420 tcggtctgtt gcctaggctg gagtgcagtg gcacgatctc agttcactgc atcctctgcc 111480 tcccaggctc cccggatcct cctgcctcag cctcctgtgt aactgggact acaggtacac 111540 gccaccatgc ctggctaatt tttgtatttt ttgtagtgat ggggttttgc catattgccc 111600 aggctggtct cagactcctg ggctcaagtg atcctcccac ctcagcctcc caaaatgctg 111660 ggattccatg ggtgagccac tgtgaattca ctgccttgag taatctgttt cttaaaggct 111720 tttgttaaaa cttgttagaa attatctgta caacttgggt gtgtatgtgt gtgtgtgtgt 111780 atctgtcttg actactaatg cagcatattt aataacatag gatcacttca gatttcctag 111840 ctttcattta ttgaattaca gtacttttga ttacttatat ttatctggaa tatagttcac 111900 attctctgtt tttaagttta ttgccataaa gttgttttta gcattctctt actgtttttt 111960 gtttgtttgc ttttgttttt gtttttgttt tgtagagaca gggtctccct aagttgccca 112020 ggctggtcta taactcctgg gctcaagtga tcctcctgcc tgggcctccc aaagtactga 112080 aactataggc attagctacc tctcccagcc tcagaagctt ttctacaccc ttcctagggg 112140 aatggggaga taagtagggg tcacttaggg agtaaatgat tatgaaaagg ggcatgggct 112200 tttgcaaaaa taggcagtag cctgtccgga ccaggtgcca agttccagcc tcttctaggt 112260 ttgactcctg ttgcctgtta acctcccctg atagattaaa aaaaagaaaa aaaaaaaaaa 112320 acctagagag ggttttcatg acaattggct tccttctgga gaatctgcat ttcactggat 112380 aagggagatt caggaaaagc ccctctgcat ttgctatttc ccaaatgcct tcagcttgaa 112440 gtaaccagca aaccaattca gcatatttgg gctggtattt cctggactcg tgtctatgag 112500 gcagtgcttc ttcaggtgct gttcaagtct tactaaattt atgtccatta gatctatcca 112560 tttctgcttc tggttgtgag tttatcaatt acttctgtaa ttctaataat tttattgttt 112620 atttcagatg tctgcaattt gagaaatatt tttctgataa aatgttcttt ttatcattag 112680 ataatgatct tctttatcct gagaatgttt ttgccctagt ttctatcttg tttgatatta 112740 attaattcag tcactcactc agcaatacct gttgagaatt tttttttttt ctgagcagag 112800 tttcgctctt gttgcccagg ctggagtgca gtggcatgat ctcagctcac tgcaacctcc 112860 gcctcctagg ttcaagcgat tctcttgcct cagcctcccc agtagctggg attacaggca 112920 tgcaccacca cgcctggctt attttgtatt tttagtagag atttctccta catggggttt 112980 ctccatgttg gtcaggctgg tcttgaactc ccaacctcag gtaagctgcc tgtttggcct 113040 cccaaagtgc tgggattaca ggcatgaacc accacacaag gcctattttt tttttttttt 113100 taagacaggg tctctctctg ttacccaggc tggagtacag tggtgagatc acggcaacct 113160 tcacctcctg ggctcacatg atctccctgc ctcagccttc tgagtagctg agactacagg 113220 caggcaccac caagcctggc tgaattattt atttatttat taattatgag atggagtctt 113280 gctgtgttac tcaggctggt ctcaaactcc tgacctcaag tgattctact gccttggcct 113340 cccaaagtgc tgggattagg cgtgagccac catgtccagc caagaacctg ttctatgcca 113400 gtcacatcaa gaaacaaaac aggcatcacc tgacaatata tatatatatt ttttggagac 113460 ggagttttgc tcttgttgcc caggctggag tgcagtggtg ctatctcagc tcactgcaac 113520 ctccacctcc tgggttcaag cgattctcct gcctcagcct ccctagtagc ttggattaca 113580 ggtgcccgcc accacaccca gctaattttt tgtattttta gtagagatgg ggtttcacta 113640 cgttggccag gctggtctca aactcctgac ctcagacaag ccacccacct cagccccaca 113700 aagtgctggg attacaggca tgagccactg cacctggctt gacagtatct ttttatttta 113760 atcacctttt tattttttac tttcaaccat tctgtgtcct tctgttttag gtgtatcttt 113820 tataaacagt attaaattga aacttttttt ttctttaaat gtaatcttgg tcttttagca 113880 gggatattta atctgttcac atttgttgtg attgctaatg taatcaaatt tggttttact 113940 accatatgtt actaatttta tatactatgc tgtttactta ctgtatttcc ccttttcctg 114000 cttttcattg tacttagttc tctttatttt ttttaagttt tatttatttt attatagttt 114060 tcttatttat tctactttgc ttatttcttc ctattgattt agaaattata cattctattt 114120 tttcttttgg tgattacatt taaaatttaa tatgcatatt ttatttgagt ctaaagttaa 114180 tggatatttc tctgctctcc ttctgatcaa aatgcctcgg aatattttgg ctctgatatt 114240 cactcccagt ctttcgtatt ccctgtgtag catgttatca gagtctagta cttaactttt 114300 tggttcattt ttttttcagt actttgtttt aaatgagaca acattataat tgatattgct 114360 ggctcattta gatttactta catgtttact ctctgctcac catcgctcct ttggatccca 114420 ctcttttctt ttggattgag tctttttatc ctgaaatata ccattggtca cttctctcag 114480 taaaggtcta acaatagtaa ctttcttcag cctttgtatg gagaacgtgt ttattttgcc 114540 cttcctcttg gatgattgct tagttgcgtt caaggctaaa agctatattc tctcaatact 114600 ttgaaaatac tattccatta atttttggtt gattttgctg cttagtaaca ttctgctgtg 114660 aagaaaaatt gttctttttt catgggtaat ctgtcttttc tctctatgtg ttctatagtt 114720 tcactattat gtgttaggtg ttgatttgtg attgtttatc tggctcctga ctgtgctgtt 114780 caatctgaga atgtaaatgc ttctttccat tctgaaaaca tctcagtcat aagtcctcat 114840 tctttctatt ctctcattag catttgttgt aaggtctcat gttccctcgt ttcttaacat 114900 cttccatctc ctacttctct gtgccatgtc ctgtatgatt tccccgcatc cattctgtag 114960 ttccctaatt cttttttttt ttttttcttt ttgaaatgga gtttcactct tgccgcccag 115020 gctggagtgc agtgatgtga tatctgccca ctgcaacctc cacctcccag gttcaagcga 115080 ttctcctgct taagcctcct gagtagctgg gattacaggc acccaccacc acgcctggct 115140 aattttctgt atttttagta gagacggggt ttcaccatgt tggctaggct gatctcgaac 115200 tttgaccgca agtgatccac ccgcctcagc ctcccaaagt gctgggatta caggtgtgag 115260 ccatgactcc cggcccctaa ttcttttatt ggccatatgt aatctaattt acttactatt 115320 tcagtgactc tgtttttttc cttctaaatc tgctgtttgg ttctctttca aattaatttt 115380 tcttttttta ttttcttttt ttaaatatat atatatattt ttattacact ttaagttcta 115440 gggtacatgt gcacaacgtg caggtttgta acatatgtat gcatatgcca tgttggtgtg 115500 ctgcacccat taactcgtca tttacattag ttatatctcc taatgctgtc cctcccccct 115560 ccccctctaa tttttatttt caatcgtgtc ctattctttc aatggttact gttcttgtgt 115620 cactttaata gctctaaaca catatatcag attctttttt aggttgtcac ttgtttccag 115680 ttcccaggta cccattggcc cgcatgttgt acttgctgac ccttggcgtg gtaggttagt 115740 tcctggcctg gttggaattt tttattgtga gctcatcttc agcaggggtt atttttgcct 115800 ctgggagtcc aggggccctg gattgtggag atgtttctgg agcactgctt tacctttttc 115860 ttctgcaaac caaggctcag ttattttagg gtcttgaaca agttttaatt tttaatttct 115920 ctatttgtga tttccaaccc atctgggtgg tatcaactta atccctgcat ttgctcttag 115980 cacaggctcc tgattcagat gattcataca aaagctttta gttacttttc agagctcaag 116040 ccagacctca ggcctccttc ctgtttcttt ggtgagcatg gttcttccag ttcccttttc 116100 atggactggc tagcttctta aggggtctgg tttggtccag tttccccctc atcttgcaca 116160 gtcctggctg gtgtcttctt tccccagggg tgttgacact ctgaccccta cttattgttt 116220 caagggctga cagccctcgg tggatacatc agcttggagg tttcctccca gccctggaga 116280 tttgctttgt ttctggcact tgggaatctc tctttcctct ttctatcaag ctgagctacg 116340 catgaaacct tttttttttt taagttgctt tagattttcc aatagctgtg tgtaatttca 116400 gcaggagtgg gtccgcatca actcagcctg ccacaaacct tattcatctt tgtactctcc 116460 aacccagaac agtcactggt tcataccaga tgctggatga atgaatgagt gaatgaatga 116520 atgcattttt cacttccagt agcagataga agcagtattc cagtgagcca tgcctcctac 116580 ctctccagga gcactgaatc aggcagaatt cacttttctt tgaggttata cgtagagagt 116640 tcccagtgaa aaaatgaaaa gagaataggg cttcttctat gcttttgttt taagtcccag 116700 aacaatagga ctgtttaact gctttgcact gcttgatata tgaaggtgga ctgacgactg 116760 agttcccatg ccgcttgctg gtggcttcac acagcatcat taccaagagg acaggacact 116820 aggactgttt acttccccct ttctcccctg ttttaagaaa agtgtgcctt tgatgagata 116880 tagccgcagg ctcttgtttt acattgtacg tcaactgctg ttgtcagagg ctggttattg 116940 atgccatgcc ctgttttaat tcacacttct ctgctaatca attacagcgt ttatccatta 117000 atcaggcatt ctgacagggt caataactgc tttttggctc ttgtgcaggg ctgcacgtta 117060 tcaagccagg aataaggccc aggagctggc tttaaaacac cgtgtgactt tcccaggctg 117120 gtggacttcc ggagcaataa acatctagtg gggatttcat atggtgggtt tttcatatat 117180 ttggtagatg ggattttctc actgaacact tcattaacag ggctcaacgt tagtgaagtg 117240 tggacaggtg tgctctgttt aagaaaaaca gaaacatcaa aaggtaatta ttgccatcac 117300 ataccaatga ctgcatttac ctaaaagtag cattaaatta tgagctttct tcttttatat 117360 taaatgttta caaacagtat cttcttggca gtagggtttg agagcaacga ctcttaaagc 117420 caaaatgttg gagctgctgc tggatgaaaa ccaatctgaa atttagatta aatagggctg 117480 taatcgtaat gtgagtcaag aggaaaatcc gtagtttctc tctggaaatt tcttgaggcc 117540 catcttttcc gtggagtgtt ttaaaccttc gtatccatgt tcccatccat gggcacacgg 117600 gcatcttcag tgccccttag tctctctata agaatttgtt acagcatatt cagatgtggt 117660 aaattgtcac agaaatgaaa acttttcatt ttagtaagga taagtaagaa acagaggtga 117720 caaggtttaa ctggagagtt ccagtttggg taggtaagtt accattcatc atgatggtta 117780 caggtttcag tgatcttttt tgtgacagat gtaccaacat ttaattgttt ttcatcaagg 117840 gcggagagaa aagacacttg tgtagatttt tcaattctcc tccgtgtcac ttggctgtcc 117900 tcaccattgt ctgagctcct ttctcttatc ctttttgctg caatgagttg tgtcattccc 117960 tcatggtcag cacttttgtt gtctttgttt tttgctgtac ctcagaagtc catcttttct 118020 ttcatctctt tcccattcat gcatgaggga acagttgtgc cctgttgtgg ggatgttccg 118080 ctgggtttca aacagtaggg tttcttttta ttctcttcta agtagtacaa tggggctgaa 118140 tgtctgttgc agaatgcaca cactaatatg ccaggttatt tggtttctaa gaagtcaata 118200 aaaatactac atttaggctc agtctttggc ttgattttcc cctatttgcc tttcaagcct 118260 tccgttatga atctgtttgt ttctgattgt aaaatataat cttgcatatt aaaccgaagc 118320 gtggaatcaa caaacacttt gaggaaaatg ttcctggcgg tggagtattt tcacaccagg 118380 cagggttggc agccggcacc ctcccttgat aagagcctgg aaacagcccc cagagcaatt 118440 aatggcagct ccgacttgga gaagatgaaa aaaaaaaaaa gaatggatcc caagttggtc 118500 ttggcaaaac tttctggtgt aagaaaccag ctcctctctg catttagagg gtacagctgt 118560 gattgttttc gtgcagactt ctcactcagt tcttgttttg gtggggagtt gagcacgagc 118620 agaacgcacc gagttacaca cacagacgca aaggccattg cagcagcaaa aggctaaaga 118680 cataaaaagt tagagatgtc ttaggacact ttgttcttat attcaggaac aatcttcaaa 118740 atcctcctta atgaggtcat aaaagaaaaa aatggaacaa gtgttccttg tgtacctctc 118800 tagggcgtgt cgttggggtc acttgccacc agtatcctat ttaaaaaggg attggggtag 118860 ttcaatcaag cattgcatta agagagagac tttgattaat tccttctctt ttcttttgtg 118920 ctatagataa tttcagtcaa tttgtgatac tttcttctta gccattgctg aggctgaaag 118980 ttcttgatgc gtcctgctga gtattagcat ttctcgggcc tacttggcta tggggaagag 119040 gcacgcactg cagacagctc tctaagcctt gacaagcagg gctggcctct acacatgacc 119100 gtgatctggg atatcggttt aggaaagagc ccgctctcag gttgctggca gaaaacaaat 119160 cttgatgtaa aagaagagaa gaccgaacag taagatggtg acttgctgtg gtaataccgt 119220 gcggtttttt taaggttctg gacctgcttc ttactcagaa gctcacagct tgggtaagtt 119280 tcaggaactg ctctcaaggg gaacaaaaga aaaggaaaag tgagggctaa caatgtgagc 119340 tttcactggg gctgttgtgg gaaagttgaa gattggcccc aggatggtca ggatcaggta 119400 gaaaactgga ttctattgtc atttgttttc ttttattgac cagctttctt gtttgtggag 119460 agggcagcag agagatgaag ggacattcta gtactatgct gtagaaactc agtgggaaat 119520 gttaactgtt ttgatgttag gatatatcta aaatgcttag ttaaactgag tcccatacct 119580 gttgtatttt ataagctcat tttggaaaat gtacgtaatg tttatttatt gtaaatgcaa 119640 ggtctgttcg gtatccgtac atttccacgc cgctgaaagg gtggatttgg ttctgatgga 119700 ctggaacggc tcccggggag gcattgtggt gtttgcgtaa atcccctttc ctttttggtt 119760 tactcatttg atgcaggagg gtcggttctt gggctgttgc tttctctcct gttaatccag 119820 ctactgcaca tgcgcacgaa ggcaacaggt taaaagtcct aatttaagat agctttgggt 119880 atggagagat aaaatccctt tttctccagt tgaagcatct gtttttcagt tgagtgtaga 119940 tgggttgatt ttcatgaatg tatacatcta atatgtttat gtaaacacat taaggcaaga 120000 tttcagaatt aatttcagag tatgttttat gataattact gctattctgc caaaagttta 120060 atagccaatc ataagaattt tcttaaatta ttattttcaa attaataagg tgttagactt 120120 ctcatttgtt ctttctggta ctgttttgag attaagaact caaagatgaa ctcattcatt 120180 catcaaatat tatttattaa actcttcctc catgccaggc tcattgtcat aattatcatt 120240 gtaattagtc tgtaacttat atttacaatg attatgtaaa tagcggaaac acctaactat 120300 cctgcttctt ggtaatcagg tttaactctc catggggtcg gtgtgttctt tctgaagcat 120360 gtctttgaat agattactcg ggccttcccc tagttcttgg aatgctaact gaaattgtgt 120420 gattgataga tttccccaga cttaaaactg gagagatcca tgggggcaga gtggttccat 120480 ggaggcagag tggtgtcatg gagaggacac aggctgtcgt catttacttt tcctgccctg 120540 aaaagggaag agccagcagc tcaggggtcg gtgtgagact taaactctga ataatgtaaa 120600 gcggctggca caggcctggc cctcagtgcg tccccccatg agcgcccctc ccccgcccct 120660 tatccctaag gcagtagtgt ctgtagggcc tcaggcacct acattctcat ttccttcatg 120720 tatgcagagg gccagggaag ttacctggtt accacttgct ctgtgccaca aaaaaggcgt 120780 gcaaggatgt acatcagaac ctggttttga ctgggcacag tgactcacgc ctgtaatccc 120840 atcactttgg gaggctgagg cgggcagatc acctgaggtc aggagttcga gaccagcctg 120900 gacaacttgg tgaaacccca tctctactca aagttcaaaa attagacagg catggtgtca 120960 cacgcctgaa atcccaacta ctcgggaggc tgaggcaggt gaatcacttg aacctgggag 121020 gcggaggttg cagtgagccg agataatgcc actgcactcc agcctgggtg acagagtaag 121080 acttcatctc aaaaaaaaaa aaaaactttg tttctgtgca caatacctca aagacttgtt 121140 aggcctgggg aatagacctg cctcatttgc ttgtttgaag cctaattgca ggtatttcta 121200 atacttccta cagtggattt ctctcgtctt ccaaatgttg cttttccaca gaattggcgt 121260 ggtaattgct gagaagaaag aacttcctta actgaatcaa gcctgcctcc acctcttttc 121320 taggattgca ggttcctttt cagataaagg tctcaaaagg gcaggcaggg cagaaggtct 121380 tctcataaaa tccgaggatt gtggtcctct gggtgcttca tctgctgcaa ccaagtagaa 121440 aaaaaggaat aaacacaaac acatttcact ctgcctccaa caaacctcct tcaggtcaga 121500 tctagtatcc aagaagtaac aaaaatagtc catctagcaa atgagccatt ttctttgaga 121560 gacaggcaag caagacacct gggtttgtct agatataatt agttatttct cccgtggcca 121620 gtatgggagt aaacactatg cagtaaacac cagctgaaga acattgtcct gtctatctca 121680 ggacagggaa tgatagatac cttttggtct ctacttaaag acagtattgc cgggtgcggt 121740 ggctcatgca tgtagtccca gtactttgag aggccgaggt gggcggatca cttgaggcca 121800 ggagtttcag accagcctgg ccaacatggt gaaatcctgt ctctactaaa aatacaaaaa 121860 ttagccaggc atggcggtgg gcttctgtaa tcccagctgc tcaagagact gaggcaggag 121920 aattgcttga acctgggagg cagaggttgc agtgagcaga gatcatgcca ctgcatgtca 121980 gcctgggcaa cagagcaaaa ctgtctcaaa aaataaaaat atagacaata ttagtattaa 122040 tattacagat cccattatat ttcttttcat gagttttgtg agggtattcc ccaaagctct 122100 gtgttttggt gggggggatt acaggtgtga gccaccatac tggccccctc ccccaataaa 122160 tataaactgg gtacttatta atacttaata tacatatgtt tcttttcttt tctttttttt 122220 ttttttttga gatggagtct cactcttttg cccaggctgg agtgcagtgg cacgatttcg 122280 gctcactgca acctccgtct cctgggttca agcgattatc ctgcctcagc ctcccgagta 122340 gcagagacta cgggtgtgtg ccaccacatc cggctaattt tttgtatttt tagtagagat 122400 ggggtttcac tgtgttagcc aggatgttct cgatctcctg acctcatgat ccgcctccct 122460 cggcctccca gagtgctggg attacaggta tgagccaact tctttttttt tttttctttt 122520 taatagagac agggtctcac tgtgttaccc aggctgaagt gcagtggtgc aatcacgcct 122580 cactgcagcc tcaacctcca gggctcaagc agtcctcgca cgtagctggg accacagttg 122640 tgcaccacca tgcctggcta ctgtgtgctt ttttgttttg ttttgttttg tttttgtaga 122700 gatggagtct cattatgttg cccaggctgg tctcaaactc ctgggctcaa agaagcctcc 122760 cacctcagcc tcccaaagtt ctgggattag aggcatgagc caccatgccc agccccaccc 122820 cagtaaatat aaactgggtc cttccttaat accttaaaga cagcaatttt cgacatattc 122880 aagacagttg ttccttctgc tttggaatgc tgagagcttc tttcctcata attgtgttct 122940 agaagttctg cagggccttg ctatgggaac cagagaaagc agaatggcca gggccatcca 123000 attgtctcct tcccagagat caggatgaag ggctgtgtta aaagatctct ctcatcttca 123060 gctggaaaca aatagtactg aaaagaatga tctggactgt ttctcttgtc ttttaaaagt 123120 gtgaggccta aagaggggag agagtatctt tgtgctgtgt tatgcctgac acattgtcgg 123180 tgaccaacag atgtacttgg ccatttatat ggggataaca tacatgtgat cttagccaaa 123240 aggccctcca aaccttcctt cagcagccct ttagattggg ctcctttgtc agtcatctgc 123300 ttgagtatca gctatgctga aggaaaagac atagggaatg gtggttggag gtggtggcag 123360 ccagagataa atgtatctct gaggcatggt ttcatctggt cagtaagatg tgtgcctttg 123420 gatctgcttc gggctaaata tcttaggggt ttggtgggct ttagaagtgt gtgtaaatgg 123480 gaggcgggaa agtgaggccg gagactcatc atcactgctc tccaccctcc agaggggact 123540 gcggaaagcg cagccagcca tcggcctgtt gacaaggcac tggcagtcac tgaaaaattc 123600 ttttcctttc tctgtcaatt agcaaatgat ggtcttctac tgataaagtt taggaataaa 123660 ggagaaagag gaagatggaa tcctggacca ctttcagcct gcacttgagt attccttatg 123720 tgttctcctg actccctggt gccactaccc cctgccaccg tcggccctgt ggcagtgggg 123780 cccttccccc cgccagcctc ggcaccgctt cagtgtggct ggtgcctcca ccaccattgg 123840 tactgtgtca gcattgctgg tgcacctgcc accgtcggtc cctcatcagc attgcccatg 123900 cccccaccac cgtcagtccc tcatcagcat tgccggtgcc cccctaccac cgttggtccc 123960 acatcagcgt ggccggtgcc tccaccaccg ttggccccac gtcagcgtgg ccagtgctgc 124020 gacccagttg ctggctggag gatggctggc cactgttgga gctgctgatc tttccaaggc 124080 cttgtcacag tggccataga tctcaaggtg cacccaggac actcaggaaa ccagcctctt 124140 ggttaggcag ctgaggcctc acttttctgc atccatgtac tcctttggta tctggatctt 124200 ccttttaaac tttgactaac acgtgtggca gaaccaatca ccaccacagc ctgcaagtgc 124260 actgaggacc tgtcaggccc aggggaggtg cagcacgctc atgggggcag cccagcactg 124320 cccaggtggc tggagcgagt cacggggaga gcagaaagct ttgggcgtcc tggctgactg 124380 gcctcttagt gagaatacag aacagctcct ggcagcactt tcccttccag ctttcctcaa 124440 gacaggccat gccaggcgaa gaggaagggc aaggtggctc cctccgggta tggagatggg 124500 gtgagcctgg ggacagtgga gcctctgagc agaggactcc agaggctcag ggagcagcag 124560 agccgcccaa gatgatagac aggagctgaa ggccagaggg gaccacgcct ggagtcttgg 124620 cgggaggagc atggacacag gaccagggag ggagccccag aggcagtgcc gaccatcctg 124680 ctaaacacac ggaacggcct ccccattctt tcccctaaag agtaggggct tgggccaggc 124740 acggtggctc acgcctgtaa tcctagcact ttgggaggcc gaggcaggtg gatcacctga 124800 ggtcaggagt ttgagaccag cctggacaac atggtgaaac cccttctcta ctaaaaatac 124860 aaaaattagc tgggcgtggt ggcagatgcc tgtagtccca gcaactcagg aggctgaggc 124920 aggagaatca cttgagcccc gggggctgag gttgctgtga gccgagatcg tgccactgcg 124980 ctccagcctg ggtgacagag tgagactctg tttcaaaaaa aaaaaaaaaa aaaaaaaagg 125040 cgggggcttg gagaggagag gaggggtcct ggttttgttg tactttgtta atatagacca 125100 gatttcggca gattgcactg tataaagaaa aataaacatg gacagaaaag ttgtatggtc 125160 aaaattgaag tagcaaagcc ttctttaaaa gttgaaatta cttttgtttc tttactaaag 125220 cacaaagtct agttgcagaa tatatgtcta tcttagcctg ctttaagaaa aaaaaaaaaa 125280 agcggctgag cccaggggct catacctgta atcccagcac tttgggaggc catggtggga 125340 ggattacttg aggccaggag tttgagatca gcctaagtaa catagcaaga ctctgtctct 125400 acaaaaataa ataaaagact gcagctgctt atattaaaaa aaaaaaaaag gccaaagaat 125460 gcctcaaagc attgaaataa aacttactga tggtttcacc agcagaacag agacattggc 125520 cactgtttaa gctgtgctag atgataaaga aggccataca ttagtttcaa agtcagagta 125580 gacagaggcg gagggtagat aggtgttagc aggatggctc tcacggacgt gctggggcca 125640 catggacagt ggacccctgg atggggaggg aggaaggaag ggcctcggac atctcctgat 125700 gtgaagaatc ctgtgttctc aattttaacc tctttgtttc tagccaagaa gtaaactgaa 125760 taacatactc cacaccagaa tggtttcact tagctttcgt atctcaggaa ctgggcttca 125820 gttctgcagt gagaactgtc ctttaattgc ttctcccctg gaggctgatg tggtgacata 125880 ctttggagca cagggcatac aggcatccct gcacgaacgg taccaggggc ttgggatggc 125940 tgcagcacat tctgctgggg ctttgttttc cttggggcta tgtttgtttt ttctttttcc 126000 cttctttctt actgtttctt ttttctggat gcattatgtt ctttaaagac tagtgatttt 126060 ccacaccaaa ttattttaga aatttcagca ttatatggca gttttttttt tttttttttt 126120 tttgagacag ggtcttacct tgtcaccttg tcacctatac tggagtgcag tggcacaaac 126180 acgattcact gcagcctcaa cctccccggg cccaagccat cagtcttcca cctcagcgtc 126240 ccccaccaac aagtagctgg gaccacaggc acatcccacc acacccggct aagttttgta 126300 tatttcgtag agatggggtc tcagcatgat gcccaggctg gtctcaaact cctaggctca 126360 ggcaatcctc cctccttagc cacttacagg tgtgagccac tgtgcctggc ctattttaaa 126420 ggtgtttttt ctttctttgg tttcggagag aaatcagttt cctgtgtatc ttaagctgtg 126480 tggatagggg gattgtgata atgggtcatt attttataat tttgctattt taaatgagtt 126540 ttaaaacctg tagccagttt ctgatctcag ggaacatacc tattaactca aggtgttaca 126600 aatatcttga cagcttaaaa attgagttaa gatatgaaaa taagatatga aaatatgaaa 126660 atactgtgct gtaatacaag aggcattcat taccttttcc ctgcccatca gtctcgacag 126720 gataacttta cacttgaccc aaagatattt aaaaatacat ccgctttctt tgaaacttct 126780 gtgtcagtgt ttttcatttg aatgattaac agaagcacat tggtttgtag gtaaatagta 126840 aataggtaat tctacttgtt tttctaattt ttaaaatgct ttacaaataa ttattaatga 126900 tactgtatga ttaaggaaag ggaatttgta tgaagctaat ttgaaggtaa ttggcttttg 126960 catttattta ttcatgtata tatttaattc gcatctgtta tgtgtcaagt atagtgcagg 127020 agtcagcaga aaaagtaatt cctaaaatca tggctcttga aatcagttat ttgtctttgt 127080 ttttcctcct caaagattac tccctgttca gtcttgttaa tgtgatcaga gatttatatt 127140 aacttttaag atctcataat cccaataatg taagatatag tagagatgag tagagaacag 127200 aacttaaaaa aaaaaacaaa ctgtaattac taggaaattg actctaccag ggaaattaac 127260 agacttgtcc aaaattgtcc ctgtagacag agagggctgg taaggctgga atgaacccgt 127320 cgtaatttga atgcttaaaa ctttttccat tttattgtca aaattattgc ctgaacttcc 127380 tttttctcct catttgccta tttcccttgc tttttatctt gtgcaccacc agtatacaac 127440 atagtggtgt ttaactactt cctgaaggca ttattagtca tcaggaacac caggtcatta 127500 tcgaagtaga taaatgggca ttccgcccat cgactacccc ttggactaat ttggaaaata 127560 tggttccttc cctcagaaga aacagcccat gctcctctgg acacttataa aatagccatg 127620 cgcacgtctc tgttccttct gaacaactgg aattaatgtg tcctgcttga tgctaaactg 127680 gagtttaatt cacaatggca aggacgcttc acctagaata tctgtccatg tgaaaggtgg 127740 ggagcagtgc agcttccatc tccctgtctg ttttttggtg ggctttcagc ttttctgtcc 127800 catgactgtt agtgactgca gcgtaacccc aaatctttca ccagatgttg tctcaccatc 127860 ttaaggaaag aagaaagttc taatggatgt tttgaatgtg ctcgactttt attttgttca 127920 gacccaaact gaatgaggca gaggttaaaa tcttttcttg ttccatctga gtaagcacga 127980 aaacctatga tccttaatct tttagaagaa aaataaccct tctctgttag tgggatttct 128040 gattcatttc ttctgccctg ctcccctgct ctgcattttt ttagtcaaat actgtctgga 128100 cttttgtgag ccaataacct ccctcctcac ctcattcccc tctcttcccc tcccctgtga 128160 tcacacaaag agcagagagc cctcaaaagc ctgggtttct gggttttgta ttttaaagag 128220 aggatgaaat acttgctgta cttcaaaaca taaaaccgat ctgttaaaac tttcccaaaa 128280 gaaactgatt ggcatcagca tagggggaat aagaaaagta agagaaattg agattaaaaa 128340 aaaaaaacaa aacggaggag aatgtaacgt tggccattgt aattcatacc aaactgactt 128400 tcctttagtg caaactagta ggcgtggcaa tgacttcaaa cctcccaagt tagggagccc 128460 tgaaatcttt ctacttactg atatctctga ataataacca gggcccatac acggggctgg 128520 gatttgatag tcgaggcctt cagtcctaac cattttgccc tgtaacttag atcaggacct 128580 atacatttat ttgtccatgg ctacacccat agacatatat tctaacgcag gggccatgaa 128640 ccaaatccca tgtactgccc atttttgtac agccttctac ctaagaatga gtcttccaga 128700 tgaatgattc gatgataggg aacattacct ttgaacccca gttaagcaaa atgctgttcc 128760 ccccaaaaga tttccgttct tctcacaagt agaactatat tactatagaa gtctactata 128820 aaatatagta gaactatatt actataaaat ctacccagtt ttattttgaa tttcaccagt 128880 aaaaaaattt gtggaaattt gtgttctcac ttgctatacc agcgcatata taacatcttc 128940 ccatttgtct ctcagcccgc aaagtctgca gtatttacta tctggccctt tcagtcagaa 129000 gtttgctgag tgctgctcta agctgtcaca aatagagatg attttgaagg gaaaaaaaga 129060 tattctcact atcattcttt gtctttgcct gaatctctgt tttagctttt tgttgttgtt 129120 gtttgtttgc ttgtttgttt ttagaggcag agtctcgctg tgtcacctaa actgaagtgc 129180 agtggtgtga tcatagctca ctgcagactc aaactcctgg gctcaagcca tcctcccgcc 129240 tcagcctcct gagcagttag gaccacaggc gggcaccatt gcacccagct aatttttaaa 129300 tttttttgta gagatgagat ctttgctata ttacccaggc tggtcttgaa ctcctggact 129360 caagtaatcc tcccacctca gcctcccaaa gtgctgggat tataggtgtg agccaccaca 129420 cccagcattt tttttttttt aagagtgaag tttctctggt taatgtgaat gtgagttaat 129480 aggctctggc ttgtgcagtg cagtgccctg agaaaactga tattaattgt acagttgtga 129540 aatgtggtat aatattgtca atagcagctt gtttaaaaaa tttagattgc aaaataaaat 129600 aaacctgtgt ttccatatat aaaacaggca gcaataatag tacctacttc aaaggactgt 129660 ccaaaggatt aagtgagata atgtaaataa gggatttaat aaatgttaaa gagaaaaaaa 129720 tctaccattg agaatatgtt tgtttgcaca agacttggta cctttatctt agcatactgt 129780 atcttagaca gatacagtat ccctaataca ctgtagatac ctaaatcatg cttctcatcg 129840 atttcagtta atacaaaata tagtcctata tctcttttca acacaattct gattttaaag 129900 gaagggtctt cttaaaggaa gaccattgtt tgtttgaaac agaattacta tatcctatac 129960 gtttcttttc tttttttttt tttttttttt ttttgagctg gaatctcgct ctgtcatcca 130020 ggctggagtg cagtagcgca atcttggctc actgcaacct ctgcctcccg agttcaagcg 130080 attctcctgc ctcagcctcc taagcagttg ggattacagg cacccgccac cacgcccagc 130140 taatttttgt atttttagta gagatggggt ttcaccatgt tggccagggt ggtctcaaac 130200 tcctgggtga tgtggccgcc tcagcctccc aaagtgtggg gattacagta tgagccaccg 130260 cacccggcca tcctatatat ttctaagata aaattttaaa gtataagtaa atctcattgg 130320 agagcaaaag atgaggtttt ttttttggtt cagaaaattt taggataatg gaggtcagtg 130380 ttttgctaac catctgtaac aaactgcagc attggaaagg gacactgtct tggtattttg 130440 aagagctaat atttatgcct gggaatcctc tacctgcatg aaatcggcag gtaagagtta 130500 gaaatatgca tgacattttc aaggaaaaaa aaaatctgtg gtgccacttg aggagatgaa 130560 atctatggtc ctgcctgttt tcctcactct gtggctccca gaatgcatct ttgactctgg 130620 agtttgtcct tctccctcca cggccagatt tcactgtcac tcctctgaga accctctcca 130680 ctgccctctt atgctgaatg agcccctccc caccaggctt caggccattg gtttctacca 130740 gtgttcacat tttttgtctg ttgccttcgc tggacctcaa cttcccccaa ggctgaattt 130800 tgtcctcatt ttcatattgc cagaccctgg cttaggtgcc cagtatctat ttgttgaatc 130860 aatgaaatac tgactaaaaa ttgtctaaca ctaaaataaa atgaaagcca aaaaaaaccc 130920 tttagatttt tctttctttt ttagatatag acaatataca tagataatca taacattatt 130980 ttagtgctga ttaaaaattc acagataagc ccaaatttat atatagcttg tctgagggtt 131040 aagttctgaa gaatatgggg ggcatcagag agttgataca aatccatctt tattttctgc 131100 agggccagct ccttagccca gcagcagctc cccggtcccc ctgtaagtgt gtttcctaga 131160 tgtggcaaaa tgcctgccat ggtgttccag gcccaagtgt ctagctcatg gaggtcagag 131220 gggaaggggc aagtgtcttc tcagccacag tcgctgttat caattgggct tcctgtgcac 131280 gaggtgcttc gtcaagggtt ttacatgtat cttttcattg acttctcaca acaatcctat 131340 tattatatcc aactcctaat atgaatctgg gatttaaaga ggttaagtaa catgcttagg 131400 gtgtcaccaa ctccaggtgt gctgggttcc aaagcccatg ctcttcactg ttaggctttc 131460 cttacctctc acctcctttc cagggaagtg gcaagatttt tggagctggc gagtctgggg 131520 actcatgact ggttgtttct ccttgaagca tagactagag gagtcatgtg cgcaagagtg 131580 ttgttaatca ctatgctttc ccctcctgag ctcaagaaaa acagaactgt caagagttag 131640 gaattgcgtc ctggtcacca ggttccttgt ttgtcccatg acccagagtg gagtcatccc 131700 aacagagatg tgctaggctg taagctgaat gtgataaggg aggcaaactg caccacagtg 131760 aagtcctcca acttttagaa gaggctagct actgtgcgcg tcaatttttt ctaacctttt 131820 tttttggtgg cttatatgca attacatacg agttacattt attgagtacc acatgcagga 131880 agtcccaggc aatgagaaat gagcttcatg gtaattgaga atgaagttaa ggaagaaaat 131940 tttattgtta atcaagggct taattgcctc cgggacattt taaataaatg ccatgcagta 132000 cttaaggagc aatgttctgt aagtgagatg caaaaattct ttaattaaac catggtgggt 132060 attccctgat tgaaatatct gcctttatct taatatttaa accttcgtga ttcatgtaac 132120 aacttaatta gggatggagt aaattaaagg ctccttgaaa gaaccaatca gttgtataaa 132180 attggttaaa agtatttctg ggataggctt ctgtgtattt gtactgatca gaacatatct 132240 ttggttcatt ttatgtttag ctgtcatctc gagtaagctg tatttcagcc tgtaggggac 132300 agatggtggc tatggcattg tatagggcag acagttatta gaatttgtct gagaaatgga 132360 tcaaatgtaa gggtttcttg gccactgaga aaggagacat ttccccagat gatgacttgg 132420 atggtacctg caattaacca ggtaggaggc tgccaagtct gttcgttggt cagtcagtca 132480 acacacctga gtgcagccac ggaaaaggcc ttgtgctcaa tggtgataag cttgtgtcag 132540 tgtcaaacta aacagaccca gagattcaag gggacttgcc agcctctgat tgtacatggt 132600 aaaaaacaaa atggaaaccc cgaaaactta ggtattcaaa tgtttagact ttactagatc 132660 actcagttta tgagtggcag agatgcctgg tgtggagctc gataaattct tgtgaaaaga 132720 aggaaggaaa tgagaatggg ggcagttgcc tgggaggagg gagggggaca aggcttgcat 132780 ctgtcactgt actgcacagc gttccctgac tagttggaca ctcagctgtg actctcgtgc 132840 tgttaacaga cattgtcatg aggattcaaa aagtgcaggg aatacacatc agtggctctt 132900 taaaaattca gggttggtgt gttttgccaa gctaacattg tgatttcatt taatccttaa 132960 aaagagtaaa attgttctca gaagatacca aaatcttaaa acataggatc atgtctgttt 133020 ttaaaaattt atttagctca aataagcagc caataacaag atgaaatagt catctaataa 133080 tggtgtttta taaatggttt tatttggaaa tttttttctc ctaatttcag tgttcgtaat 133140 atgaaacagt caagcccttt aaaagggatt gcattttcaa ataaacacac ttagacacac 133200 cgtgtgaact tagtacttga ggaaaggaaa tgaggggagg aaaggaaaat attttaagtc 133260 atattttcat gaaggactct gtggtattca acacgtgttg gcagactctg gccaggctca 133320 aaaatgatgg gtcgcgttct gcctactgtt ttaggaccac actggccagg gtgtccccca 133380 aggtgccttt ctgcctctgg aatccctgtt acgggcccac ggaaagcctg tggatgccca 133440 ccagctgctg aggggtccct gtgatggttt agatctgaaa tcatactcag ttctttggcc 133500 atgttctgga aggctagaat tgttatgtca ctgtgagtat ggaaatccct ttagtattct 133560 acatgataat tcagagcaat taattccatt ctaatttcca tgccctagaa gaactgtact 133620 tgtggccggg catggtggct cacgccggta atcccagcac tttaggaggc cgaggtgggt 133680 ggatcacctg aggtcgggag ttccaagacc agcctaacca acatggtgaa actccatctc 133740 tattaaaaat acaaaattag ctgagcatgg tggtgcatac ctgtaatcct agctacttgg 133800 gaggctgagg cagaattgct tgaacccggg aggcggaggt tgcagtgagt caagatcgta 133860 ccattgcact ccggcctggg caagaaaagc gaaactccat cttgaggaaa aaaaaacaaa 133920 aaaacaaaaa aactgtattt gtaaaaacct gaacaaagac tatcatatct gcacaaagtc 133980 tgtgaagaaa ggaaaatgag ccatgtgtac tccagagcaa ctagctgctt cccagtggcc 134040 ataaatatgt cttgtttctc aaccatttcc aaatgcttca aacttaaaga aatttgtacg 134100 tgcccaggaa cgctctatct tcgccttctc tggcattagt tctatgattc tttaatgttg 134160 tgggagatat ttatgaaatc atttcctctg actttagtga ctctgccttt gagagctcaa 134220 tggtaaatac acaatcagca tgtgtgctaa gaggctcgaa agtctcatga caaatgctgt 134280 cctgtacctt gcagggcaat gatgtctgta agcatctttc cttaagcacc cactcactcg 134340 ctggcttgga tacagtgagt ctcaagacat cttaagaaaa ttgccatctg agcatcacgc 134400 tgcaggatct ggtgttagat atttttgtgg ctacgtgggt tcttactcat ttcccctctc 134460 cgtctgtctt gtattttcta tgtgccggtc ttgccttagt tcatatgcat tcaggagaag 134520 gtatcattag cgacttgacg cccatattat gacttaacga gctggaaagt ccacacgtat 134580 agattctgca tctctcaaac tgagattttt gattcgtaga caggtcgccc gtagactctt 134640 cccagaggct ttggctgctt gggacacaga ttgtaatcac agtaattagc actgaatttt 134700 caagtcctgc tctccagctt gacctggcag catttaacgg cgtgcacaca gctggatcaa 134760 tggcaggaat tgaaggaccc agttgtgggg ctgctcctgg cagcctgtga tgggcaccgt 134820 ccctggagaa ttccaggaaa gcatcaggga caagggatgg tgcagggacc tgggtgcgaa 134880 agtaaagaaa tatgatattt ataaagcacc tgtcgatggg aatcctgttc aaaattgtta 134940 ctggagacaa attgaagtac agacttctgc ctgaaattca ttatcaatga attcattttt 135000 ctccttcttg cttagttcag ttttgggtat ttctaaaatg ttctttgtta aagtttacac 135060 ttcctttccc taaaagaagt acttacagat aggaatctta aagctagtgg gaaagaactg 135120 taggacacaa aacagatact tcagtggcac aaatggggca aagaagcacc catgcctgtt 135180 atgaagtaaa ttctctagga agtttggtgg tgttggggag tcagggactt aagctcagat 135240 aagccagaag gcactcctct gtcacccact tcttcatagt cccagggagt gtgtcacctt 135300 accaggccac tagaaggaga gagtgacaag aacatggcag tttggcacgg cagaccccaa 135360 ccttcatcca tcgagggctt gtgattttgt ggggatactt gaaggctgac tgctgaataa 135420 aaggtttaaa cttacaggaa atacctctca acacaaaacc atttgagcat atgtatcttt 135480 tttttggggg gtgggggtcg ggggacggag tcccactccg ccgcccagac aagagtgcag 135540 tggcatgatc tcagctcact gcactctagt ccgcgttcaa gtatttgtag tagagacggg 135600 gttttgccat gttgcccagg ctggtcttga actcctgacc tcaggtgatc cacctgcctt 135660 ggcctcccaa agtgctggga ttataggcat gagccaccgt gcccagccaa gcatatgtag 135720 tgtctctaac catatgatca atctagttga aaaagcatgg taggcagagt tttacaatga 135780 gagctttttt ttaatgttta gtttccttag ggacagaaac attattgttc cattctacca 135840 ttctgcatca gtagttcgta tgaggttgta cttttgcctt tgtcacttgt cagcatttgc 135900 actgacttaa gttgttagaa tatttatgtg gaaaatgagg gcaattctgt gtgtaaatat 135960 ctcacttgac aatcatttta tgatttgaat gttcacttgc aatgagaccc tgacatgttc 136020 acacgtgcta gttttcagct gcaattacat ttgccactaa tttgtacctt ggaacgtgtt 136080 tactgaagcc gctatggagc actcggttcc gggagccctt tcactcatca actgcttcta 136140 ggtcgcacct tgcactggga gaaacctggt gtctttctgg aaaattcctt accattcaac 136200 agcttaccca gtcatgcatt tagcactttt tcctgaaatt ctttcataaa taagcaggaa 136260 gccttctttg ctatttttat tataaaaggg gaaatgagga taaaagttac acatgttgtt 136320 attttaacat ctagtcttgt atttgttgaa gagttacgct tttacttaaa aacaaaacca 136380 gagacttatg cctgttgcca gcctctgtca atgatggctc ttcattcttt taaagttcac 136440 agcagaaaac actgtgttaa gctcttcttg gctttaaaag ccaaattaga cacccaaaag 136500 tctcagcact ttaaaatcct ttaaaagatg atttaagtaa atcactttag aaatctatgc 136560 ccaaactttt aaaaagtact tttcacatct tgcctttaca agtaactgtg gaattagaca 136620 caccataaat gtactctgta ttttcttaat aagtttgaat tttcggaaag cctttatttt 136680 tatattatag agccaacacg gctgttggat gttgaagaga cccagccaat attattacac 136740 atttctttct taagtgcaga acttggattg ggacagggac tgtttggttt ggaaaacatc 136800 atctgttttc cttctcctcc tcctttcctt ctgtgtttat ttcatttggt ggctgcaagt 136860 tgcaggtttt tttccacttc acacttttgc tagccctctt cttttcttct gctttacaat 136920 ttgcactaga agagggtagc gggctttttg tttgggttcg ggtttttttc tttttctttt 136980 tctttttttt ttttctttgc atcttccttc ctttccacag agagattgct gctgaccaaa 137040 tttaaaacac tacagtgttt aggatccctg cagggccatt ttaagtattt ggagccataa 137100 agggccccaa gccataacta cctgaattgc ttttaattac acaatatagc tgcatcattt 137160 tacttcagat tctttttgat tgatgctgca gggcaattgt aaccgcgaat gatgggatta 137220 agtgcctctt gaagtgactt tagcttcttg tgggaacaaa gggaaagagg agaacactta 137280 gtcccttttt tgcctgagct gcctttttct tcacttgcgt ataaagaaat acaattaaca 137340 aacattatcc ccagaggtaa attgaaatgt acatgcagac aagaaccgct cttgactgca 137400 attagacata tatgatctaa ggtattctgg ccattcatta gtgctaattg tttgagaaac 137460 aagcccagaa caaatgatta aaatgtaggc gccataactg ggattattag catgtgtgat 137520 aaaatgcaca ctctgtggct gtactgagga aacgctttgg aaagcagctg tgatttgaag 137580 aatggttggt tcggctctgt ggtgagctct cttggtgttt gctcaagacc tggtggtgtt 137640 tataacaaac aacttacatc tttctttctt aattagtggg aatcacaatg gtattttgta 137700 atttaattgt aattacaaaa ttgtaataaa ttgtaataaa ttgtaattac aatattggta 137760 ttttgtaatt taaaatccta tcgctttcct gcgcctttgg gttgctcctg cagtctagcg 137820 gtattgcggg gactcgggat aacctgaatt cttagatttt gcttctacac tccactttct 137880 ttttttttct cttctttctt tttttttttt tttttttttt ttgagacgga gtttcgctct 137940 gtcacccagg ctggaatgcg gtggcgcgat atcagctcac tgcaagctcc gcctcccggg 138000 ttcacagcat tctcctgcct cagcctcccg agtagctggg actacaggcg cccgccacca 138060 cgcccggtta attttttgta tttttagtag agacggggtt tcaccgtgtt agtcaggata 138120 gtctcgatct cctgacctcg tgatccacct gcctcgccct cccaaagtgc tgggattaca 138180 ggcgtgagcc accgcgccca gctacactcc actttcttta aaatgttgga ggccagggag 138240 aaccacttga aagtttgctc ccttatttga cttttgaata gttactcatc acacctacac 138300 tgtagtgtga gggaaaagtt ctgagatatc ctctggcatt tggaacttct cttaccatac 138360 agagacctgg caggggtgac ctagtcagac gtaaaccatc tgggagctgg ctggtccatc 138420 tgagcggcca gcagtctgca gggttcttat gactgaaggg actggttttg ggatgtgcca 138480 ccccagacct aaaatcgcta agccctctag gacctgtaca agtggagaac gcctaatcca 138540 agttaagtga ccaaaggagt aagcaccaat tcagagagat agatggcgat taaatttcct 138600 atggaaatgc atttaggagc tgggacctag cactcagtga gagagatggg aggtacccag 138660 ggcaagggaa agagaagata tgagatgaaa gaggaacaaa ggagcaatag agggctcaat 138720 ggggagtgtg ctgagcaggc agaagctgca tcccaggtag taggtctgtc tgctactggg 138780 tgcttcaggg ctccctattt ggagctcagt gtttctctgt cctccacctg cattgctgca 138840 tctggagtca caggcaggac catttggaga ttgtccattt ggtgccatga aaacctgcaa 138900 caacctttca atctcaagtg agaccacttg agattgtcac ccaacatact tccccagcca 138960 cctatccctt agcatgtcat tagcacattc caagggaaga caaatatcag cgttagctag 139020 agaggatata agattaaatt tgcttttaaa gtcagctacc aaattcaaaa gacaagcaca 139080 aaagattttc tggttctctc catctctaac tgacctattc tgtctttctt gccattgtta 139140 cagaaaatgg aattaagtca caaataaacc ataacataga ttattataga catacagctc 139200 ttaattttca gttttattct ttttgtattt acaagaaaag tgttactctc tgaatttgac 139260 cagttagttc cactggaaac taagtaactg tgtatattcc ataagagtgg gtttggcagg 139320 gagctgaaaa taaaggggaa agaaactgtt ttgcacttta aactggggca ttgctgtgtg 139380 gtactgaatt aagaaaaaaa aatattaagc tcccttaaaa ttagaggaag ttctaggaag 139440 tcttacctta aatagatatt taaaggaatt agtgcttata gcacattaaa catacttcaa 139500 aaacaaaacc caactatgtt agaaaagcct tcacgatcac atccatatgt ttagttttaa 139560 tttgcatcac acttagctct gaataattaa gaaggaaaaa acaatcttaa tcttatcatg 139620 ggtcctatac aatcaaagcc acatacacgt gattcgtgat cacagcttgt attcacagct 139680 ttcgtgtgtg tggtatgggt ctggcaatta gactcagact gtgttttttt ctaaaaatta 139740 ttcagtgcta gagagtgatc aatattaaac tctcccaaaa atgtacaaat cagaataatc 139800 aagggactgt ggctaaatag aaaaaaaaaa agtcaaaatt ctaagctatg taacattttg 139860 gcctcatttc attgagattg acacttgaaa ggaatttttg agagaatcta ggatgaaaac 139920 ggagatttca ttaacccagg tcattttcat gacagttacc aaaaaaaaaa atttttttca 139980 gatgtgggaa gaactatttt ctcaaaattg cagagccatt ttctagaaga aaaaaaaaat 140040 gctcttccat gattactttc atatcaaagt acccagtctt gggggagatg cattaatttg 140100 acacgtttag cagcctttga gcttttgaaa aactctgtaa aagaatccat ggttacatct 140160 gtcaggttga cagtctttcg tgacctttaa aaaaaagtta aggagaaact gatcttttta 140220 gttcacattt gctcagttac ctctaactga acaagctagg aaatagtcat ttcagcttta 140280 aatactattt tttttttttt ttttttacat agaatcacca gtactaatgg aatctctaaa 140340 tggaagagtt tagtggatat ttctggtggt ctcatggtaa tgatatgtcc tgtgctcttc 140400 actggctatt tcaatacatt agctactaaa tattgtcttt tctgcacctg tttttagaat 140460 cagatctcct taggaagatc aacagtgggc attctaacta ggggcctctg ctttgaatgt 140520 tcctcattgg ccagtaaggg aacaagtttc ttctttgttc cttacacaca gagttccagg 140580 atccaaaatt attaatgatc tctacagagg caaagagaac tcaggctggc gtgtcctttc 140640 tgttttaatt acaatttacc aaatcctccc atgtcatgca cttgacaggt gctatacctc 140700 atagttccca atgctgggat tacacttgga aatccatcta tcaaatctct ttgggtagag 140760 tcctgagcag tcattcttgg accaagttct cagcgacatt aacagttaac tattaatgaa 140820 caacatcctt tgactccttt gtgtttccag gagcccctgc tagaagcagc ccagaaacag 140880 aagagatgct aatcgcattg tgtgcctgaa cgtgttcagt gaaggagcgc aggtttccct 140940 cttgacctcg gagtcacggc aggaaaaaaa atccctccag ttttccgtca gataaaacct 141000 ctgctcctcc ttctctcacc aaaagtagag ccagaaagtg ggattaaggc aaatacccac 141060 taacaggcac atgcgccatt gtcattccct cttccacaca aaacaaggag ctttgcagaa 141120 aaacaaaaag ctcctctcct ctcccccccg ccccaccccc atgctccctt tcttttcctc 141180 ctcccctcct ccttcgttcc taccctccca ctttcttatc caccccggct ttccctcagc 141240 tgcccccctt ctcctttttc tggttttctc tctcacctgc tctcaaatgc cctctccccc 141300 gccttcctct tcctccttgc ctcctgccgc tctgatttag gccaactctt tcctcatcct 141360 catcctcctt tcagaaaagc gtcagtgttt accctcaaag gagctaccgg gtgcccatgt 141420 gctgtgaggt ggagccactc cgggagctgc cacggccaca tttatagaaa gatgaaccca 141480 cacgggagac aaacggggct ctctctgttt tcatggaaaa actgcccttt tatttgggat 141540 tcatgaatgg tcaccacagt ggtatgggtc ttcctgttcc tgggacttcg ctgacataag 141600 ccatgcacct gcctggacaa ctagggctgt gtggcctcac aaggcagatt cagtgagtga 141660 caacaaagtg ctaacagaca gtagcttctg gtccgtgttt gtacagccta ccttaggagg 141720 ccttccttag cgagggccag cgtgtggtgg actcaatatt tgttgaatgt gtgttttatc 141780 ctgaatctga tcaatacgtt tttgtttatg aaatgatagc atggatgtga taaggccaat 141840 agatggggta attttatttt tttaattgtg gtaaaatata cataacataa aatgttaacc 141900 attttcaagc atgcagtgca gtggcgttaa atagtacatt atgattattg tgcgaccatc 141960 cccaccaccc atctccagaa tttttcatct tcccgaactg aaactatacc cattagacaa 142020 aaactccaat tctctgctgg ccgcagtggc tcatgcctgt aatcccagca ctttgggagg 142080 cccaggtggg cacttgaggt cagaagttcg agaccagcgt ggccaacatg gcaaaacccc 142140 aactctacta aaaatacaaa aattagccag gcatggtggt gagtgcctgt attcccagct 142200 acttgggagg ctgaggtggg agaatctctt gaacctgaga ggcagaggtt gcagtgagcc 142260 aagattgtgc cactgcactg cagcctgggt gacagagcaa gactctgtct caaaaacaaa 142320 aactccaatt ctcccctggc aactatcact ctagttttgt gttttttttt tttttttttt 142380 tttttttttg agatggagtc tcactctgtc gcccaggttg gagtgctgtg gcacgatctc 142440 ggctcactgc aacctccgcc tccccggttc aagcgattct cctgcctcag cctcctgagt 142500 agctgggatt acaggcacct gccactacac ccagctaact ttttgtattt ttagtagaga 142560 tggggtttca ccatgttggc caagctgatc tcgaactcct gacctcatga ttcacccggc 142620 ttggcctctc aaagtgctgg aattacaggc atgagccacc gcgcacggcc tctagtttct 142680 atctgtatga atttgatgac tgtaggcacc tcatggaagt gagaatcgta gaatgtctgt 142740 cctattgtgt ctggcttatt tcattcagca taatgaagaa ctttaatttt tgacatggat 142800 gcttgtttgc tctctcattc tgtgtgaaaa aagacttcca ggcaggtcgc ctgtaatccc 142860 aacactttgg gaggccaagg tgtgcggatc acctgaggtc aggagttcga gaccagcctg 142920 gaccacatgg tgaaacccca cctctactaa aaatacaaaa attagccagt gtggtgtctg 142980 gtgcacctgt agtcccagct acttgagagg ctaaggtatg agaattactt gaaccctgga 143040 agtggaggtt gcactgagcc aagatcacac cactgcactg cagcctgggc gacaaagcga 143100 gactctgtct caaaaaaaaa aaaagaaaag aaaagaaaaa agacttccgt cattgggaca 143160 cttgtaggaa cgtccctcgc ccctggtgtc ccgatggtct gaggaggcag tacgctgcag 143220 tgagacagta taacgcaaac tttactaaac cggacaagaa taaggattct gcttttttct 143280 tgactcttgc caagcctgtc ctttatctga tgtccaaccc ttttcatggg tttccatgac 143340 aaatagagtg gccagggtag accaggaggg ccgttccttc ccggtgcccc tgctttgtac 143400 caggaacccc acaatagcca gaaggctggc ctaggagttg cccccatcct gtaccctgag 143460 tccttcctta gaagcaaagc catggtggac cacaaactgg cttcccttgt gtatctgctt 143520 tgggcacaaa agaccatgtc ttcatttcag cacaaaacag tgcacttcat tgaggtgtga 143580 tataattgct tcaggagaga gtttgctctg aaaatgtctt ctcggccttc ctgaagcagg 143640 ctgcacgctt atttatattg gcaccacatg ctaatctcac gaatggccct gttccgccag 143700 tgggaggaca aatagctgtt cttttgctcc cgtgtccatg gaaagctccc ctttctcctt 143760 gcatggttgc catagtaacc aaaaaaaaat agttcttcaa aatagggaag gaatctctca 143820 gggtacttgg gaacttagca aagtgagaac ataagtaggc ctcaattatc atagatgctg 143880 gtgtaaatac ctagttatta atagtcaaag cgggttgaaa ttggtaggtg aattttgctg 143940 tcacttaaga gagtagggaa agatgggtga ataggctctt accttcactc agtactacag 144000 attcttctgt aaccattgga attgccagac gaggtcagac ccacaggcca tacaacacag 144060 aatttagttt ttgttggcac agaacagaga aagaggcagt gacagagcac agttatgctc 144120 ctgcgacccc ctcagccccc tcaaaggatt ggagatacag cgctaagtag aggaatccat 144180 tacgaatctg tcatactgct gtggatatgt gcacactttt ctgtaagaaa tttttatttt 144240 caacctttat cagcccttag agtcaaaatc tctttaaagg agctaaaggg ccacagcatt 144300 tttgtgtggt attctacata gaaatttact gatggccagg cgcggtggct catgcctgta 144360 atcccaacct ttagacaggt ggatcacaca aggtcagggg ttcgagacca gcctggccaa 144420 catggtgaaa ccccgtctct accaaaaatt aaaaaattag ccaggcatgg tagcaggcac 144480 ctgtaatccc agctactcgg gaggctgagg cagaagaatc gctggaacct gggaggcgga 144540 ggttgtggtg agccgagatc gtgccactgc actccagcct gggtgaaaga aggagactct 144600 gcctcaaaaa aaaaaaaaag aaagaaattt attgatgtat tatttttaaa taatgccctc 144660 tttttttaaa aaaaaaatct tatgtttaag aacatataag aacttactta aatttattag 144720 aaattgtgga gacaatttcc aaaggatata taaaagatat atcttttttt ctggttgtaa 144780 aacagctctt cagtggttac tggacacggg tacagcttaa aaattttaaa aatatttgaa 144840 tggaaatgta cgatgatata gccactgtgg aaagaaatat ggcaattcct caaacaattg 144900 aacatagaat taccagatga tccagcagtc ccacttctgg gtatggaatt gaagcacgga 144960 ctccaacacg tatttgtaca gccatgttcg tagcagcact attcacatta gcaaagaggt 145020 ggcagcatcc ccagtgtcca ttgacagatt tatggatatc aggatgtggc atatccatac 145080 gatggaatat tattcagcct taaaaaggaa gaacattctg acatacgcta taacatggtt 145140 gaagcttgaa gtttttttgt tttttttttt tagatggagt ctcactctgt cacccaggct 145200 ggagtgtaat ggtgtgatcc cggcgcactg caatctctgc ctctcgggtt caagtgattc 145260 tcctgcctca gcctcccaaa aagctgggat tacaggtgtc tgccaccata cctggctaat 145320 gtttgcattt ttagtagaga cggagttttg ccatgttgac caggctgatc ttgaactcct 145380 gacctcaggt ggtcctccta cctcagcctc ccaaagtgct gggattacag gcgtgagccc 145440 ctacacctgg tgaaccttga agatattatg ctgagtgaaa taaaccagtc acaaaaggac 145500 aaatacagtg tgattccatc tatgtgaagt atttagagta gtcaaattca tagagatgga 145560 aagtcaaatg gcggttgcca agggccgagg ggaggaggga atggggaatt catgtgtaat 145620 ggggccagag attgagtttt gcaagatgaa gagttctgga gatagatggt ggtggtgatt 145680 gcacaacggt gagaatgtac tcagtgtcac tgaactgtac acttgacagt ggttcagatg 145740 gtaaattttg cattatacat attttaccac aatacaaaaa tagtagtgtt tcacatggtg 145800 gggagtataa aatgatagcc tatagatcag ctcaaggtag gaaacaacga tcttaaaatg 145860 attcatggat tattgtttta ttgctgttca aatcaggaag ttataaaact ttccccaggg 145920 ttcagatcgc cagtcccttt ccacagttac ctttgctcac tacacacatt ccaactcaca 145980 acacacacaa catacaaaac cctgggcgta gacagtgcag agggccacgg atgggagagc 146040 aagccaggca ctctcatatg ccgctggtgg gagtgtaaat tagcacaact ccattgggaa 146100 gacagtttgg tgaagccgac ggagagcatt aaataatcac actgataacc tttttagccc 146160 tctgaggaca gaggctaatg gaaacttgtg gccctttctc cttgaacatt ccctagcctg 146220 ccacccagcc tagcttggag tccattcttt cattcattca gcctgcatgt gccagacatg 146280 gtgctgtgag ctccatgtat ggctttgagc caagcagacc aagtccctgc ccacaggggg 146340 cctgtggcac atgggctgtg gagttgcaca tgagtgatac cagctggggc tgatttttgc 146400 agaaaaggaa tttctgggag gctggtggac aggctggaga ataggaaaat ggacagtgac 146460 caaactaagc tcctaagaac acagcccagc ccaggccagg gcagtctggc cagggtaaac 146520 cagactgtct accctgcccc ctcctgctgc tgtcctcctg ctgctgtccc tgcgctgctg 146580 tcttccctcc tgccatcctg ggcacttgct gggggcacct ctttccttca ccggctccca 146640 ccttctttgt gtcaccccct catggctcaa aggccccacc tgcagtatct catgggccaa 146700 gcttatgctt gtggcctctc cctagctttc aaaggatgtg gagaaggacc gtggggtctc 146760 tgcctccacc cccaccaaac aggaagggtg ttcctgtctg ggacagccaa aaaggaaaaa 146820 ttctctgaac ccagtggaag acagacagtg aacaagtaaa caaagccaat aattcatttc 146880 aaaaggggaa ggcctgtgaa gggaagggcg gggttctgga ggacagcatc ccaggagggg 146940 gcatggggaa ggtcctgctg aggacagggc atgtaggctg agccttgagg gatgagaggg 147000 tggcagacat gctgagatcc agaagagcct tccagagagg gaaccactta tgggatggtc 147060 ccgaggtgag caggaagatg tggtgtgtca gggaactggc agcagatacc tgtaactgag 147120 ggtggtaagc agaggagacg gatgggccag gcagccagga gcctgccaat ctgggtgaga 147180 catttggttt ttaatgtgag aacactggga agccatggaa ggggctcaag cagaggagca 147240 tcatgatttg atttgtgttt tttaaagtcc agactggctg tggtgtggag aagggactgg 147300 agagggacag aggccccagg aaccagtcgg gagtaaggtg gtggtgtctt gggccagggt 147360 gggaaagata cagtgcagag gtgcgtgcaa ggcacagtta acgcccatgt atgttagctc 147420 tccagtttgt aatgtagagt aggatgtaag tcccatccta aaggccctgg cagggagctg 147480 gaatgcatgg aatacctgat tgatactggg tttgattagt acgtctttaa aatttattga 147540 tacatttacc tacatttatt aaaatgactt agaatttatt gtgctgttag agttattatt 147600 ttagtggcaa tctcttttta acttcatttt gaatttaaag agtgatgtta tgactttcta 147660 aagccctgaa ccaagttatt ttctgcactt agtcaagtct ggactgctac ttatatgact 147720 caaaagtatt atgacattgg ccgggcgcgg tggctcatgc ctgtaatccc agcactttgg 147780 gaggccgaga cgggcggatc acctgaggtc aggagttcga gaccagcctg gccaacatgg 147840 tgaaacccca tctctacaaa aatacaaaac ttagctgggc atgatggcaa tgcctgtaat 147900 cccagctact caggaggctg aggcagaaga atcgcttgaa ccggggaggc agaggttgca 147960 gtgagccaag atcatgccat tgcactccag cctgggcgac aagagcgaaa ctcggtctca 148020 aaaaaaaaaa aaaaaaaaaa aaaaaaagta ttaggacttg gccgggtgtg gtggctcatg 148080 cctataatct cagcactttg agaggccaaa gtgggcggat cgtttgagcc caggagttcg 148140 agaccagcct ggtcaacatg gagaaacccc atttctacaa aaagtacaaa atttagccgg 148200 gcatggtagc acgtgccagt agtatcaggt aatcactact tgggaggctg aagtgggagg 148260 gtcacctgag tcagggaggt ggaggttgct gtgaactgtg attgcatcac tgcactctag 148320 cctgggcaac agcgtgagac cctgtctcaa aaaaaaaaaa aaaaaaaaaa agaggagaga 148380 tggagtctca ctctgtttcc tagactggtc ttgaactcct ggggtcaagc aatcctctca 148440 cctcagtctc cgaaatagct gggactgcag gcacacacca ctatgcccag ctcttctaga 148500 tgatcttttt ttgttgttgt tgtttttttt tttggagaca aagtcgcgtt ctgtagccca 148560 ggctggagtg cagtggcatg ttctcagctc actgcaacct ccacctcctg ggttcaagtg 148620 attctcctgc ctcagcctcc caagtagctg ggactacagg cgtgtgccac catgcccagc 148680 tttttttttt tttttttgta ttattagtag agacggggtt ttaccgtgtt ggccagactg 148740 gtctcgaact cctgacctcg tgatccactc gcctcagcct tccaaagtgc tggaattaca 148800 ggcatgagcc accccaccca gcctagatga tctctttttt tttttttgag acggagtctc 148860 actctgttgc ccaggctgaa gtgcagtggc gcaatctcgc ctcactgcaa gctccgcctc 148920 ccaggttgac gccattctcc tgcttcaaac ccccgggtag ctgggactac aggcacctgc 148980 caccacgccc ggctaattgt ttgtattttt agtagagaca gggtttcacc atgttagcca 149040 ggatggtctc gctctcctga cctcgtgatc cgcccgcctc ggcctcccag agtgctggga 149100 ttacaggcgt gagccaccgc gcccggccct agatgatctc ttttaagtag atactcattg 149160 ttatgatttc tgtcctcctc ttttctgggc cacagggggc ccaggaggaa gtgtacaaac 149220 catgtcatgg cagccttccc tgtgggctcc agtgaagttg ctcatgtgtc ttggcccttg 149280 gtgactggtc tctgatgccg tactaatggt cagtggacct gtgatctgtt cttggggtac 149340 aggaaatgca tgaggtgtgc ccagtgggtg tgatcatggc cctgcagaca gggcagctcc 149400 tgcctcttct ctccctgttg ctgtctgtca cccaacacca gccagcctgt tacctctgat 149460 atgggcgccc tcactcctgg actctgacag ctcccttgca ggcacactgc caaagggtca 149520 gtcgaaactt ctggattctt ccatcctcag ggaatggata gcatgccact gttgcccttc 149580 tctgcctgag caatctatat tgctgtgtct gctcttctct gtgccccacg ttgatgcaga 149640 gctcccatga agtctcccag agggtgagtg ggaagttggc acaccccctc agtttggaca 149700 ttcccattgc ctctctagtc actgtcactg tcctgcatgt tcctgggatg ggggagtaga 149760 ccaggcagaa ccttcagccc tgtctcatta cttgggctct ccccaccgaa ccgctgtcag 149820 catctgaagg gctttgtctt gcccgtgaca aggacttcac ttcaaatccc ccattccttt 149880 ctcactctgc ctcctaagaa ttctatgttc agacccttaa gctgctggaa attataagac 149940 ttcttctcca ctaacaaagg cacgtttatt atctcactgt ggacttgata ccagaatcta 150000 gcatgaagct cctagttcag cagggacttc ctggtgttca ccccattctc acccctgcac 150060 ttctacaatg atggccatgg attcagtggg tggggatgtg aagcaacatg attttcaaac 150120 aagggaaact tctgctcatc tcaaaattat catttgatca gtggaaggtt gtgtaattga 150180 tacctatctc ccctgcctaa atgtaatagg attaaattct ggttactatt aatgttcagc 150240 aagcccaagt cctttttggg atcggtaaga caccttagtt gtacttacaa cccttaatgc 150300 agagattctc atctttggct gtactttgga gtctttctgg tagctttgaa gaagtgctga 150360 ggcctgggac tcaccataag agtgatttaa ttggtttgga atgtggcctg gtgttttagc 150420 ccctaaagca agcttgtcca acctgtggcc tgtgggctac atgtggccca ggacagcttt 150480 gaatgtggcc caacacaaat ttgtaaactt tcttaaaaca ttatgagatt tgttgttgtt 150540 gttgtttgtt tgtttgtttg agctcattgg ctagtgttag tgtattttat gtggagccaa 150600 gaccgctctt ccagtgttgc ccagggaagc caaaaggtta gacagtcctg gactaaagct 150660 tcccacatga tcataatgtt caggcaaagc agagatcctt aaactagcta ccagctaagt 150720 aaagaagcca ttcacttggg tttagaagtc atgtactaaa ttgtatcttc aaatggacat 150780 gcgcttcttt gattactatt gctattttga attactgcag tttgaatgtt attttattat 150840 tttttttcag acagggtttc actctgtcac ccaggctgga gtgcagtgac gtgatcatgg 150900 cccactgcag ccttgacccc caggctcagg cggtcctctc acctcagcct caggagtagt 150960 ggggaccata agcttgcacc accacaccgg ccaattattt aaaacatgtt tgatagagac 151020 agggcctcca tgtgttgccc aggctggttt tgaactcctg ggctcaagtg atccttctgc 151080 cttgacttcc caaagtgctg gcattacagg cgtgagccac catacccggc caagtgttat 151140 atattttttt aatcaaaata cttttcttta aatatagatt tttttcaagt ttgtggaaac 151200 ctgattgagt ttcattgctt tcacagcatc tacttgtaca taatggtagc atttgactca 151260 gttagaaatt tttactgagg caaaatttct tgcattaaga cagtggctat attggcattc 151320 gctagtgcag ctgccctcca gctcagctgc gcattagaat caccttggcc acttttattt 151380 tatttttatt tatttattta tttcgagatg gagtttcgct gttgttgctc aggctggagt 151440 gcagtggcat gatctcggct cactgcaact tccgcctctt gggttcaagt gattctcctg 151500 ccttggctgc cattgtagct gggattacag gcaccggcca cactatgcct ggctaatttt 151560 ttgtattttt agtagagtca gggtttcacc atgttggcca ggcaggtctc aaactcctga 151620 cctcaggtga tccacccgcc tcggcctccc aaagtgttgg gattataggc gtgaaccact 151680 gcgcctggcc accttggcaa cttttaaacg ttccatagcc taggttttat cccagaccaa 151740 ttatgtcaaa ctgtctgtgg ctgggactct gccatcagca tatttgaaaa ttccccaggg 151800 gactgcaacg tgccaccaag tttgaaaatg aataacctgg agacatttat gtgatatgta 151860 tcacctggaa atcttgtcta tacgcagatt ctctgatgaa gaaggactgg gatgggctcc 151920 aaatcctgca tttctaacta gctctcacat gacagcaata agagagcaat ggtgctgacc 151980 tgcagcaaca gctcacttaa gtggcaagga cctagaaagc ttaaaaagcc tgggtcctgt 152040 tactaatgaa tttaatttga tggcactgag tagggtccag aatttgacaa ttttgaaaag 152100 ctccccaggt gactattata ttgaatcccg ggttgggaac cccgtcatgc tacgggccag 152160 ctatgcctct tgttatataa atggttaatt aatggcatca ggtgaagggg gaagggagac 152220 gacaaaaaca aggccaggtg ggggcccccc tctgggatgg catatctaaa aaaggtccct 152280 ctttagagag aactcaccat aaggctacca gattttttca acgcatctta agcccctgct 152340 ttgcatattt tttgaataca gttacatatt gactatctag aggccctaat tccaaatatg 152400 taagataaaa taaaacaagt tccatcttgt cacctgctgc aattgtattc atacgctgta 152460 gacagtgctg aatacaactc aagcacagaa cagattttgg aacagctggg gatgggggaa 152520 ggagaggact caccagcagg aagggaggag ggaggcgtgg taaagccttc cttctccgga 152580 acggtgactg ccgtgactgg gcttctgcca cctgcccagt gacagccccc ctccagacca 152640 cagagtctgc aacagaacct gaagccccaa tcctccttat acgtttcttc tttacattat 152700 ttcaaacagt tttgttgcct ttgatctttt cccctagagc ttgctcagtg ctggccttgt 152760 gctgtcctgc ctctgattca caggctgttc tttggggtgt ccctctctga acctctgggg 152820 atgccctttt ttgtgccacc tcctgactgt gcttagcaca gtgcagctca gggccactgg 152880 atacagctgt gcagggtgtg ccctagagag ggcacctggt gaggggcaca agaggggctg 152940 ggccagtcat gctctacact gtgctgcagc aggagctaga gttgcctttc tgctcttcca 153000 tttgctggaa agcactaagg ggcacctttt tccagtttgc atgtaagtgc tgccttgtgt 153060 gctagtggag gcccagagca ggtcacccat tggtgcttac taagtgctca ctgaatgaat 153120 gaatgcatga acaaaataac aaaatagagg caataaagat aaataagaag ctttcatagt 153180 catttaggtc aagtttaagg aagccctaaa ctagaatgta aatgtgtgat ggaaagcagg 153240 ggataaacag aggagcagaa gcaacaggtg gtggattgga ttaaggttca aggatggcaa 153300 aggagagagg gaataaaaat tatctcctac ctgtagtcac cagtaatgct tgactcttcc 153360 acaagaagaa cagggacagt ggggtgcggg tgagttctac gcacccaagt ctggagaggt 153420 ggctttggtg aggcaacaag ttaacaggag tgatgcacct ctgatgtcag gccctgaaac 153480 aagcagtgca gagagatgtg agaccacccc caccccctca gagagctcat gctctaggta 153540 aggataccag acacagaatt tctggtgctg ggctgtgtca accagcagca cccatgggtg 153600 acaagtgaca gttaataata ctatagtagc tgtatctacc tactacttgt tttactcttc 153660 gggatgagct ttcatctgtg agaagtagct gttatgttgc ttctcattga agaagacatt 153720 gatgcttcct accccatctc ctgactgcca gtcaaaacat taggttgaat catataaaat 153780 taccattttg taggtcaaaa atggtcaaat atcagcaatt tcatatagtt cagcttaata 153840 cattccacta tttttgctgt ttgagacctt ttaaatgctt ttattggctt aagtcaatta 153900 taaaaggaga tttttgatta ccggttcaat ctccttacta gtcagactcg ctatttatct 153960 aggttattca gattttctgt ttcttcacag tttagtcttg gaatttgtcc atttcatcta 154020 ggttattcaa ttggttggca tacaattgtt catagtactg tcttatgatc ttttatttcc 154080 atagaatcag tagtaatatc cccatttcca ttgctgattt tagtaatttg agtcttcttt 154140 tttcttagcc tactagctaa aagtttgtca gttttgttga tcttttaaaa aaatcaactc 154200 ttcatttcat tgattttctc tgttgctttt ctgttctcaa cttcattatc actgctctta 154260 tatggctttt ataattgcct atgcatttac ctttactaag atgtttattt cttcatgtgg 154320 gtccaagtta ctgaccagca ttttttcatt tcatgttttc atataccttt gggccttcat 154380 ttcactctgc acctaagcat ttcttgcagg gcagctctac tggtgacaaa ctcccttggc 154440 tttttaaaat ctgggaatgt ctgaatttct ccctcacttt gaaggacagt ttttccagac 154500 ataggattcc tagctgacag gtcttttcct tttagcactt tgaatatatt ggcccattgc 154560 cttttggctt ccaaagtttc tgatgaaaaa tctgctgatc atcttactga agataccttg 154620 tatgtgatga tttgtatctc tcttgctatt ttgaaaattc tttccttttt tattgataag 154680 agatatacat agtttcagga tacatgtgat aatttaatac agtcatataa tttgtaaaga 154740 tcaaagcacc atactcagga tatctgtcac tttaaatatt tgtctattct ttatgctaga 154800 accatttcag ttcttttctt ctagctattt ggaaatatac aatagattat tgtaaactac 154860 agtcacccta ctgatctgtt taacactagg tcttacttct ttatcaaacc atatatttat 154920 acccataatc aacttctctt catacccact tttcctctac ccttctcagc ctctggtaac 154980 cgttaatatt ttctgtcttt gggggctgga tgcagtggct catgcctgta atcccagcac 155040 tttgggaggc cgaggcaggc agatcacgag atcaggagat caagaccatc ctggctaaca 155100 cagtgaaacc ccatctctac taaaaataca aaaaattagc cgggcgtggt ggcgggtgcc 155160 tgtagtccca gctacttggg aggctgaggc aggagaatgg cgtgaaccgg ggaggcggag 155220 cttgcagtga gccaagatcg tgccactcca ctccagccta ggcgacagag tgagacgcca 155280 actcaagaaa aaaatatata ttttctatct tcacaagatt tgtattttta gctcccacat 155340 atgagtgaca acatgcaata tttgtctttc agtgcttggc ttatttcact taacgtaatg 155400 acctccagta caatccatgt tgctgcaaat gacaggattt cattcttttt tatggcaaat 155460 tttacacaca cacattcacg taacagtttc tttatgcatt gatagacact ttgattggtt 155520 ccatattttg gctattatga atagggtagc agtgaacata ggagtgaaca tactcatttt 155580 gatatattca tttcctttct tttggatata tactgagtag tagaattgct ggatcacagc 155640 acagttctct ttttagtttc tttgaggaac ctcaatactg ttctccatag tggctatact 155700 aatttacatt ttcatcaaca gtgtacaagg gttccctttt ctccacatcc tcaccagcac 155760 tcgttactga ccatcttttg gatcaaagct gtttcaactg gggtgagatg atatcttatt 155820 gtagttttga tttgcattcc tctgatgact agtgatgtta ccattttttc atatacttgg 155880 ccatttgtat gtcttcattt cagaaatatc tgttcagacc ttttgtctgt ttttaaattg 155940 gattttttgt tttttgctgt tcagttgttt gagctcctta tatattctgg ttattaattt 156000 cttgtcagat gggtagtttc taaatatttt ctctcattca gcagattgtc tcatcatttt 156060 ttttattgtt tcctttgctg cgcagaagtt ttttttagct tgatgtaatc ccatttgtct 156120 tttttgcttt ggttgcctgt gcttttgggg tcttacacaa aaatttttgg ccagaccaat 156180 gtcctggagc atttccccag tgtttttttt ctagtagttt caaagtttca ggtcttagat 156240 ttaagtcttt gatccatttt tacttgattt ttgtgtatgg tgagagatag gggtctagtt 156300 tcattcttct gaatgtattt atccagcttt cccagcacca ctgaagagac agttctttcc 156360 tcactgcatg tttgtggaga ctttgtcaaa gatgagttgc tcataaatgc gtggatttat 156420 atttgggttc tccattctgt tccactggtc tatgtgcctg tgtctgtttt tatgcgggta 156480 ccatgctgat ttggttataa taactttgta gtaaattttg aagtcaggta gtgtgatgct 156540 tccagctttg tttgttttgt tcaggattgc tttgactatt cagagtctct tgtggttcca 156600 tataaatttt agaacatttt tccttttcta tgaagaatat cattggtact ttgataggga 156660 ttgcattgaa tttgtaaact gctttaagta gtcttgtcat tttaatgata ttaaagctgt 156720 gaacatagat tagaatatct ttccattttt tgatgtgtcc tccaaaattt ctttcattgg 156780 tgttttatag ttttccttgt agagagatct tttatttatt tggttaaatt tggttgctag 156840 gtttttaata ttatttatag ctattataaa tagaattgct ttcttgatat ctttttcata 156900 ttgttcactg ctggtgaata taaatgctgc tgatttctgt atgttgattt tgtattttgc 156960 aactttactg aattagttca tcagttctaa cagctgtttg gtggaatctc tgtttttcta 157020 agtataagat catgttatct gtgaacaagg ctaatttgac ttcttctttt ccagtttgga 157080 taccctttat ttttttctct tgcctaattg ctctggtcag gatcttctag tattatatta 157140 aatacaagtg gcaaaagtgg gtatccctat cttgttctag atcttagagg aaagtcctta 157200 atttctccct gttcaggatg atgttagcta tgggtttgtc atatatgacc cctatatttt 157260 gaggtatgtt cttcttatat ctggtttgat gagggttttg atcataaagc gatgctgaat 157320 tttatcaaat gcttttttgg catccattga aataatcata tagtctttgt tcttggttct 157380 gttaatgtga tgtatcatgt ttatttattt gcatatgttg gatcatcctc gcatccctgg 157440 gattaatctc acttgatcat ggtgcatgat ctttttattc tttttttttt tttttttttt 157500 tactagacag agtcttgctc ttgttgccca ggctgtagtg cagtggcacg atctcggctc 157560 actgcaacct ccgcctcccg agttcaagcg attctcctgc ctaagcctcc cgaatagctg 157620 ggattacagg cagatgccac cacgcccggc taatttttgt attttcagta gagacggagt 157680 ttcatcatgt tggctaggtt ggtctcaaac tcccgacctc atgatctgcc cgccttagcc 157740 tcccaaagtg ctgggattac aggcgtgagc caccgcaccc ggccgatcat ggtgaatgat 157800 ctttttaatg tgttgttgaa gtcagttggc tagtattttg atgagaattt ttgcatctgt 157860 gttcatcatc ttagttttcc ttttttcgtc atgtccttct ctggttttgg tatcagggta 157920 atgctggcct catagaatta gcttgggagt attggagtat tcattcctct tcaaaaaaaa 157980 aaattttttt ttgagacagg gtcttgccct gtcacccagg ctggagtgca gcagtgcagt 158040 cacagctcgg tgcagtcaca gctcactgca gccttgatct gctaggctca agggattctc 158100 tgcctcagcc acccaagtag ctaggactac agatgtgtac caccatgcct ggctaatttt 158160 ttttttcttt tcttttgggt agagacatgg ttttgccatg ttgcccaggc tggctcttca 158220 gtttttttga agaatttgcg taaaattgat atttgttatt taaatgtttg gtaggatgcg 158280 gcaataaagc cattaggcca tgtggggatt tctttcatgg gagactttat tatggcttca 158340 gtatcactac tcgttattgg tttattgagt tttcctattt cttcatggtt caatcttggt 158400 agatgtatat gtctaggaat ttatccattt cttctaggtt ttccagtttt gttggcatgt 158460 agttgttcat agtagtctct aatgattctt tgtatttccg tggtctcaat tgttatgtct 158520 cctttttcat ttctaaagtt atttatttgg gtcttccctc tttttctttt ttctcggtct 158580 aaccaagggc ttgtcaattt ttgtatctta tcttttttta ttttgtgaga cagcatctta 158640 atctgttgcc caggctagag tgcagtgaaa tgatcatggg tcactacaac cctgaactcg 158700 tgggctgaag caatcctcct cctgcctcag cctcccaagt atctgggtac tataggcatg 158760 caccaccatg cctggctaat tttttttttt tttttaaaga tggggtctca caggtctcgc 158820 tatgttgtcc aggcttgcca tgaactcctg cctcaggcaa tcctgctgcc tcgacctccc 158880 aaagtgctaa aattgtaggt gtgagccacc atgcccaacc cttgtattta tatttaattt 158940 accaatgggt tttatacctt taaatgtttt tcttttcttt ttttttttct ttttgcactt 159000 tagtgttttt ttcttgcaga ttgaataact caatatttag tgtttcttgt aagatggtgg 159060 tgaattctcc ctgctttcat ttgcctggga aaaacatatt tgaaggataa ctttgctgaa 159120 tacaatattt ttggatggca gttttttcag cactttaaaa atgtcattct gctgcttccc 159180 cctggcctgt atggtgtcca ttgagaactg ccagacacat tggagtgcct ttatatgtta 159240 tttgctgatt ttctcttgct gcttttagga ttctgtttgt ccttgacctt tgagagtctg 159300 attattatat gtcttgaggt agtcttattt gggtcaaatc tgtttggtgt tctctaacct 159360 tcctatacct ggatatttat atctttctca agttttggaa agttttttgt ttctcttttt 159420 ttttgaataa gctttctacc ccttgcactt gctcaactcc ctattgaacc tcaataattc 159480 ttaaattttg tcttttttct ttcctccctg tgtcacccag gctggaatgc agtggtgtaa 159540 tcacaactta ctgcagcctc aacctcctag gctcaagcaa atcctccctc tcagcctccc 159600 gagtaactgg gacaacaggc acgtgccaca atgccaggct aattttttgt attttttcta 159660 gagacagggt tttgccatgt tgcgcagact ggtcttaaac tcctgggttc aagcaatcca 159720 cccgccttgg ccttccaaag tacggggatt acaggcatga gccactgcac caagtcgagt 159780 cttttttttt tttttttttt aaagacaggt tctcattctg tcccctgggc tagagtgcag 159840 tggtgtgatc aaagctcact gcagtctcga actcctgggt tcaagcagtc ctcccacctc 159900 agcctcctgc atggctggaa ctacaggcat gcaccacaat gccctgctag tgtttttatt 159960 ttttgtagag aggggggtct cactatgttg cccaggctag tctcgaactc ctgccttcaa 160020 gtgatcctcc tgcttcagcc tcccaaagtg ctgggattac aggcatgagc caactcattt 160080 ggcaaatttg gtcttttgag gtaattttct gtatcttgta ggcaatcttt gttgattctc 160140 attttttaaa gatttttttc tcctttatgt attttcaagt agcctatctt taggctcaat 160200 gattcttacc tctgcttgat ccattcttct ttggaaagcc tctaaggaat tcttcagctc 160260 tgcaaacata tttctccatt ctaagatttc tgcttgattt ctttttatta tttcaacctc 160320 tttgctaagt ttatttgata aatttctgaa ctgcttttct gtggtatctt aaagatcact 160380 gagtttcctt agaacttcta ttctgaattc ttggttagag agcttacata tcatcctctc 160440 atttagagtg agttgctggt tccttgctat gtccctttgg ggagatcatg attccctgtt 160500 tgctgttgtt tcctgttgat gtgtatgtct ttgcattgaa ggattattca tttaatctag 160560 tcttctctgg ctggcttgtt tttgtatttt attggataca tttgcttaga ggctttttgc 160620 tgctgggtca ctgcctcctt tttagctcta ggtggagcct taaacccagg ttcacctcag 160680 ctcttagtaa actatcagaa cgctgctctt cctgaatggg ggaggtcccc aggggatttt 160740 cttggcaggg tgggaaggct ggctaggggt ccatgcccag gggatctgtg ggacaaacct 160800 cctatagtgt ggtactgcta aacagccact ctgatttggc atctcctttt gctgagttac 160860 acaacagaga ttccagagct ggggatggta gtcccacctc cctgctttgc ctctgtctgt 160920 cctcagggat atttctccct tcaggcactt gcgatgcttc ccatggatta aggcagagca 160980 ggcctcctgc cagggaaccc aagatggtag agaagctgaa tgtccacctc aattgcactt 161040 tttccagtgt agaaaccttg agttggagga aatgtttttg catgcctggt gatcggcata 161100 atgtggggaa tgttgttatg gatgtagaaa tccaattgtc ttaccatctg ctcagggttt 161160 tttctggggt cctgggaact gtctcatctt catatttgag ttctgaggtc cttctggtga 161220 taatttcagc actgtatatt tgtttttatt tttctgttgg ggaggggtgg gtactaaagc 161280 cagcttactt ctatgccacc atttcagaac tggaagtctt tcacttttga aagtttgatt 161340 ttagtgtgtc tagatgtggg tgtctttgag ttcatcttac ttggagttca tttaacttct 161400 tggatgtttg tattcaagtc tttcaccaaa tttggagagt tttcagccat tatcttttca 161460 aaatactctt gctacccttt tctctctcct tatccttctg gaattcccac agtgtgtgtg 161520 tgtgtctgcc tgatggtgtc ccacaggtcc tttaggctct attcacttct cttcagtctt 161580 ttttctgatc ctcagacttg ataatttcca ttgtcctctc ttcaagtttg ctaattcttt 161640 cttctgcctg ccaaatctgc ctttgaatcc ctctagtgaa tttttcattt caattattgt 161700 acttttcagt tctggggttt gtggtatctt tttaagtttt ctatctcttt actggtattt 161760 ccattttgtt catacgtcat tatcttgatg tccttcactt cttcctttag ttctttgagc 161820 atctttaaga cagttgtttt aaagtctttg ccatcaggtc tctttcaggg accgtttctg 161880 ttgacttatt tttcttcctt tgactgggcc atattttcat ctttcttcat atgtcttgtg 161940 atttttttgt tgttgaaaag tgaatgtttg aatctaacag tgtggtatct agaaatcaga 162000 ttctccccct cccctgggct cactgttttt gtttacttat ttgatggttg tatactgtgt 162060 gtatgctgag gaaaatataa gcctgaggta taaatgtaag gtctcctcaa gtcttttctt 162120 tttctttttt tttttttttt ttttgagcag agtcttgctc tgtcacccag gctggagtgc 162180 aaacggtgct atctcagctc actgcagcct acacttcccg agttcaagca actctcctgc 162240 ctcagcctcc agagtagctg ggattacagg cacctgccac cacaccccgc tgatttttga 162300 atttttagta gagatggggt ttcaccatgt tgcctaggct ggtctcaaac tcctgatctc 162360 gtgatctgcc cacctcagcc tcccaaagtg ctgggattac aggtgtgagc cactgcgccc 162420 gacctctttt tttttttttt tttttttttt tttttttttt aaagacagaa tctcactgtg 162480 tcacccaggc tggagtgcag tggtgcaatc tcagctcact gcaacctccg cctcccaggt 162540 tcaagcaatt cttgtgcctc agccacccaa gtagctggga ttacaggcat gtgccaccac 162600 acctggctaa ttttttgtat ttttagtaga gacattgttt caccatgttg gctaggctgg 162660 tatcaaactc tgacctcggg tgattccccc tgcctcggcc tcccaaagtg ctaggattac 162720 aggtgtgagc tagcactccc agcttctcag gtcttttctg agcctttctc tgggcatcca 162780 tggtcatttc tattttcccc tatatatatg tgtttgtttt tgaatgtcct agtctttaat 162840 gtctggcttc taaaagggaa aaaagcaaaa aattaatggg ggaggtgctg gccctttaaa 162900 ttacctggag gtcacttcag cccaagggag aggggcttgc aacattggag ggacatacaa 162960 taacagtggc tctcagcctc tttgtctgca cttctgtgat tagaaccagc aatcagtgat 163020 cagagcacag atccttgata tttggagggt cagggtcttt gtttctgcct accctggctc 163080 cctcaagcta tgtgcaggtt gctccaggaa catgggcaca gctgcctacc atgtgactga 163140 gaggtggggg atgggtagct gctgctctgc taagagctga agttgaccaa aattaactac 163200 tatttaatat ccaagccttc cccgagaagt tgcaagcctt caatagattc caagtggttt 163260 caaaatagtt acagcaggaa gattttgcta atgcagttgt ctgggtgggg aagattgctg 163320 gtgctttcta ctccaccatc ttccccctct cttagatttt cacatgtgtg gttacattaa 163380 atcctgatga gcagagaatt tgccccaaac atttcttggt atttttaggg aaatgtatat 163440 gttgcaaatt ctagtctcca gtgtgaatga taagtaaaat gtggttgttg ctgttacatc 163500 attatgtttt ttccctgttt ttagataaac cagatatttt caatcaatga aaaacgatga 163560 cagatatttc aggcagtctt caattagctg gcaataatat gttttatatt aaatgaaatg 163620 tttcgtaagc catgtacact tttaaaatcc atctctatct caccatacct cacatgatac 163680 agtgcttatg ttgtggcaaa ataagaccca gactcaagtt ttagaattcc ttaaggtaag 163740 gtcggctaca agaaggaatg agggccccca cacaaacttg caaggcccca aaagacagtg 163800 atttttcttg agatacatta agtcacaagc acactaatca tggtgaaatg ttacaaccgt 163860 gcaaagtatt tgatagtgtt aactactgat gtccagggtt ttcatgaaga tatagctgac 163920 atatatattt tttaagatca tgctatttat ctagggagag taaaacatca gtttgccagg 163980 gttttaactt ttctttcttt ttcttttctt tctttttttt tttttttttg agatggagtc 164040 tcgctcttgt cgcccaggca ggagtgcagt ggcgcgatct cagctcactg ctcactgcaa 164100 cctccacctc ccgggttcaa gggattctcg ctactcagcc gcccaagtag ctggaattac 164160 aggcgcccgc gactgtgccc ggctgatatt tgtattttta gtagagacag ggtttcacca 164220 tattggccag gctggtctcg aactcttttt ttgtttgttt gttttttgag acggagtctc 164280 gctctgtcac ccagggtaga gtacagtggc gcaatcttgg ctcactgcaa gctccgcctc 164340 ccgggttcac gccattctcc tgcctcagcc tcccgagcag ctgggactac aggcgcccgc 164400 caccacgcct ggctagtttt ttgtattttt agtagagacg gggtttcact gtgttagcga 164460 ggatattctg gatctcctga cctcatgatc cgcccgtctc ggcctcccaa agtgctagga 164520 ttacaggcgt gagccaccgc gcccggtctg gtctcaaact ctctacctca gatgatccac 164580 cctcctcggc ctcccaaagt gttgggatta caggagtgag ccactgcgcc cggccgggtt 164640 ttaacttttc ttaactggca gttatttttt ttgagacaga gtcttgctct attgccaggc 164700 tggagtgcag tggtgcgatc tccgctcact gcaatctcca cctcctgggt tcaagcgatt 164760 ctcctgcctc agcctcccaa gtggttgaga ttacaggtgt gtgccaccac acccagctaa 164820 tttttgtgtt tttagtagag atggtgtttc accatgttgg ccaggatagt ctccatctcc 164880 tgacctcatg atccacccgc cttggcctcc caaagtgcca ggattacagg cgtaagccac 164940 cacgcggggc cctttttttt tttttttttt tttttttttt tttgaggcaa ggtattgctc 165000 tgttgctcag gctggagtgc agctttgcga tcacagctca ttgcaacctc atcgaccttc 165060 tgggcttaat caatcctccc acctcagcct cctgagtagc tgtgactaca ggcatatgca 165120 ctatgcctgg ctaatttttg ctttttgagt ttttttcctg atagagccga gattttgcta 165180 tgttgcccag gctgatctca aactctgggc tcaagtgatc tgcctgcctt ggcttcccaa 165240 agtattggaa ttagaggcgt gggccaccac acatggccta aggcctaatt ggcagtcttc 165300 atgacataga acttcatctc ttatgggcag ggttggcttc atggacatgt aatttgtgct 165360 cttagacata cctagtgctg atataatatt cttctgttgc cattgtgaag ttcttaataa 165420 attataaaca aagacctctg cattttcatt ttcaccgggc cccgcaaatt gtatcgctcg 165480 tcctgattat gggagctgat ttcatcttcc tttaccatat cgtatgagct aaagcatggt 165540 tttcacggga taaactatgg aacaggcaag ggtggtggta agccaaagga gcttctggcc 165600 aacacttttt atttctacca gagactgaac ttggtatgat aggcaaggga aagaaagagc 165660 atagtttaga agcaggcagg ggctactgac agctagagat tctccattaa taacaacagc 165720 agctgctggt actcctgcta cacccacgac catttcaagt agctaaaata tctgccaggc 165780 tctggctaag tgcttcatgt tcattatttc ctttaactta atcttctcaa caacctacaa 165840 attgagtatt atttttatag atgaagaatc caaagttacc agtaattaag ttgcctacaa 165900 ttatagaggc attcactgtc cttcctactc acttaaaaag aaccagtcta tcttgtcttg 165960 ttaaaattgg atgtgaatca ccaattttca ccctttaaaa gatgtattgg cagggcaagg 166020 gccatagact tcgttagttt tttttttcta cttttttact tttaggtata attgtagata 166080 gtattgttgt ttagtacctt ttggatagat attttctttc ctttttctcc atagatgcta 166140 tctagacagt ataacaatac tggaagtgtt ttccaagaag aaatacatac accctcctct 166200 ttgtctcaga agatgtcagt aaacagtcct atctattttt taaacctcag ccaaaataac 166260 atttagttca ttgattatct ctgctattat tgttttctta gtttttatgt gtgattgtat 166320 tctaccataa ttttaaaaga ttatccagct aggcatggtg gctcatgcct ataatcccag 166380 cattttggga gcccaaggca gatggatccc ttgagcctag gagttcaaga ccagcctggg 166440 caacatgacg aaatcccatc tctacaaaaa atacaaaaaa ttagccaggc atggtggcac 166500 acacctgtag tcccaactac tggggaggct gaggtgggag gatcacctga gcctggaggt 166560 ggaggttgca gtgagccgag atcacaccac tgcacttcaa actgggcgac agagcaagac 166620 cctgtctcaa aaaaataaaa ataaaaaaag attatccatg tgttctattt taattttgca 166680 ttaaaatata gtttttcaca agtttataaa tacagaaatc tcattctgga ctaaccccaa 166740 tcacgtgtct tgcaggaaag cgtctctagc agctgatatc cccagacttg gatatagttc 166800 ctcatcccat cacaagtaca tcccccggag ggcagtgctt tatgtacctg gaaatgatga 166860 aaagaaaata aagaagattc catccctgaa tgtagattgt gcagtgctcg actgtgagga 166920 tggagtggct gcaaacaaaa aggtaatggc atgattttag tatgagaaaa agaaaggtat 166980 tgaaatttgc ttctcttccg aatagtgaca ttgcccgcta tttggaaaga ttctaccaca 167040 ctcatctttt gctgattatt aacaattctt tgatctgctt ttatataggt tctaaatgtg 167100 tatctctttt ctctgagaga aaggaagaat cccaccaaaa tatattttaa aatcacgacc 167160 ttcagtagat gagactatgt gtatgtatag ataaaaagat ggacaatcaa ttttggccat 167220 gatgtttgcc ggtctaggta aatgagtgac atcaggggtc cccaatcccc aggccatgga 167280 ccagtacagg ccacaataca ggcctgttag gaactgggcc agaacccagg agatgagcag 167340 tgggtgaaca agcattatgg cctaagctct gcctcctgtc agatcagcag tggcattaga 167400 ttctcaagga gcacgaccct gttgtgaact gcgcacgtga aggatctagg ttgcacgctc 167460 cttgtaagaa tctaactaat gcctgatgat ctgaggtgga acagtttcat ccgaaaccat 167520 tgcgccgccc cacctcccat ggaataatta ccctccacaa aacaggtccc tggtgccaaa 167580 aaggttgggg accactgaat tagataattc taaaattgtg gtgtaagatt ttcagactga 167640 taaaatgcaa ctaggaagtt ctttcttctt cttaccacca ggtatactga gtaatggtct 167700 tttctcttct gggatacgtg tcaagagaat aaaacatagt ttttcatgga taaatcacca 167760 ttttctctac ttaatttaag ggaaatgaca catagaacct tagtggttgg ctgtagcttc 167820 tggcttattt cctcatggcc tgaccaaaga gatgagcctt agaaaatatc caacttgtag 167880 gccggatgag gtggctcatg cctataatcc cagcacttta ggaggccaag ataggagcat 167940 cacttgagct caggagtttg agaccagtct ggccaacata gcaaaacccc atttctacca 168000 aaaaaaaaaa aaaatttagc caggtgtggc ggcgtgtacc tgtagtccca gctactcagg 168060 aggctgaggt ggtagaatca cgtgagcccg agagtttgag gctgcagtga accatgatcg 168120 tgccactgca ctccagcttg ggcaacagag tgagaccctg tctccaaaaa agttttaaaa 168180 aaacaaaata accaatttgt aaataggtac aaaagactct tactgcgtga ctgtatagta 168240 gttgcttttt attttgtttt gctcaacttt gttttctatg tttttctaat gaacatggat 168300 tcattcaatg attagttgag atatataaat cattataaca ataacttaca tttgcatgga 168360 acttttaaag ttaaaaacat gagttcgctt gacctttatc tatccaggcc ctagacaatg 168420 aggttgggct gggaatgggt cgtggggcgg gggatgaggg agctggctct ctggatttat 168480 gcctacttga aagtttcttg cgccaggtga cctgaaacaa cgtggctgta ctatacaatt 168540 ttctggatta attgcttttt ctggagtttc tagcaaatat ttgccttaat tttaaagaaa 168600 aaatttaatt tccagtatct tcctaatggt caaactaagg ctttccaagt atttggaaaa 168660 ggattagaat gagcctgtgg aatctaaaat gtctactcaa catctttggc atgtgccaag 168720 gaaaatacta ttaatccttc tcccagagat taaagtaaat aggccttttt ctgaaggctg 168780 taatatgatt tcagtatgct ccttcccata actcatgtag tgcactccaa gattcgatgc 168840 taacttgtaa ttccagttct gtgtgaccca gggcaattca ctttacttct ttgcctcaat 168900 ttcttatctg tactgtaggg atgacaatat cttcttttgt cagggacagg gtttattatg 168960 agaaaaaagt tgataaagta cctgggagta gcttgatttc ctataggaaa tagataaatc 169020 ctgtagtaat catgattaga ggggaattta ttgtagcatt gtagcacagt gagccattag 169080 gtgccctgat aaacttctaa ttatagttct tcacaaatct tgaggttgtc ctccaatacc 169140 cacctgagaa tgttttctgc cactcaaatg agttggaaat atagtctatt tctgctttac 169200 atttccttat tgtttatctg ggttccgaag ccatccttat ctccatagta gtagcagctg 169260 tgctaccact taggggaaac ctgaggagga gaagggaaag aagagttaat gattgcccac 169320 catcttgaag tacatatgtc cacatcgagt ctttactagg acattttcat tctcctaatg 169380 cagctggaca ttgcaatgtg ctagacatac tgttttaggc atcctaagct cagagtcagc 169440 taaaatttca ttaaaaaaat tttttttggt cgttgtgttg cccaggctgg ggtgcagtgg 169500 tgtcatcata gctcactgca gcctccaact cctgggctca agcagtcctc ccacctcagc 169560 ttcctaagca gctgggacta tacgcaccta ccaccatacc cagctaattg ttttattttt 169620 tgtagagata gggtcttgct gtgttgccca ggctgttctt gaactcttgg actcacgtga 169680 tcctcctgcc tcagcctccc aaagggctgg gattacaggc ataagccatg atgcccggcc 169740 aaaattctct ttttcatcca tagaaacttc tggaaagcca agctggtctt tgtttaaaat 169800 aataataaca ataggccggg cacggtggct cacacctgta atcccagcac tttgggaggc 169860 tgaggtgggc agatcacaag gtcaggagat caagaccatc ctggctaaca tggtgaaacc 169920 ccatctctac taaaaaatac aaaaaattag ctgggcgtgg tggcgggcgc ctgcagtccc 169980 agctactcgg gaggctgagg caggagaatg gtgtgaaccc aggaggcaga gcttgcagtg 170040 agccgagatc gtgccactgc actccagcct gggtgacaga gcaagactcc atctcaaaaa 170100 aaaaaaacca aaaaacaaat aataataata ataataataa tcttggccgg gtgcagtggc 170160 tcacatcagt attcccagca ctctgggagg ccgaggcagg cggatcactt gaggccagta 170220 gttcaagacc agcctgggca acatggcaaa acctcatctc tactaaaaat acaaaaaatc 170280 agccaggagt ggtggcacac acctgtaatc ccagctactc gggaatctga ggcacgagaa 170340 tcacttgaac ctgggaggca gaggttgtag tgagccgaga ttgccccact gcacttcagc 170400 ctgggtgaca gagcaggact ctgtctcaaa aaaaaaaagt tgtttttttt tttttcttaa 170460 aatctctatc taggacttaa ttttatctga catatttcac atcatagccc tagcctgtca 170520 aggtcttttt ggattttgat ttcattatcc aacatttata ttatctgaga atttgacatg 170580 cacatcatat gaaaatttaa caagtttcag ggaaattttg aagaggttgg ggccaagtgc 170640 tgcacaagca tgccgctaaa aacttctttt ccggtttatt gaacagagac gtatatagtg 170700 ctgacgatat gctgggcgct gtaatttgca tgacaagcca ttgaggtgct atgattacat 170760 tcattttaca agtaaggaaa ttgaagcaca gagatatcca gttcatgcac gttttttttt 170820 ttcatagata gagttttgct attgttgccc aggctggagt gcagtggtgc gatctcggct 170880 cactcactgc aatctccgcc tcctgggttc aagtgattct gctgcctcag cctcccaagt 170940 agctgggatt acaggtgtgt accaccgtgg ctggctaatt ttgtgttttt aggagagatg 171000 gggttttacc atgttggcca gactagtctc caactcctga cctcaggtga tctgcccacc 171060 tccgcctccc aaagtgctgg gattacaggc caccgcaccc agcccccacg cccaacccag 171120 ttcgtgaatt ataccatgaa tgtgcttatt cagaaaccta actctcctaa aatccaatct 171180 tttcacgcag atattatgat attttcatca aatgcctttt caaaatgaag atatgttccc 171240 aatctacttg tccaaaaata ccttctccct caatacctcc acctaaccag caaagtgagg 171300 tcaggtaaat gagacttgtt cttgaggaaa cccaagtcag tacctcattg ctaccacctc 171360 tttgtaaact gttggaaata caaaaatgct gtactgagaa ttttctttct tccttttctt 171420 ttcttttctt tttttttttt tgagacagag ttttgctctt gttgcccagg ctagagtgca 171480 atggtgtgat ctcagcttaa tgcaacctcc gcctctcggg ttcaagagat tctcctttct 171540 cagcctcccg agtagctggg attacaggcg catgccacca cgcctggcta atttttgtaa 171600 ttttagtaga gacggggttt catcatattg gtcaggctgg tctcgaactc ctgacctcag 171660 gtgatctgcc cacctcagcc tcccaaagtg ctgggattac aggcgtgagc ctgagaattt 171720 tctgttacaa gtgctgtatt acatatattg ttatttacat accttatccc atttacatat 171780 gttatcttaa tccttatagc aatgttttga aatatgtaca aggtcacatt gccattaaat 171840 agcagaacca agatttgagt ctcctagaat ttttgccagg aaccagcctc cagctcacct 171900 gctcgtgtat gtcctaaccc acgtttttcg tctttcttgg aaagtgagtg ccttggcttc 171960 tttttatctt tagtcagctt cctgttctcc attatctctc caaggtaact gacaggagct 172020 ctgtgttccc atctgcagac tctttcagtg ttctgggact gggattatca tccatttaga 172080 cctaggagct tcaattcact ggaaagtcca gataagcctg aaacttctca aatatctcat 172140 attctctttt ctttctcaaa gtcacctctt aatcatgttt cttatttgaa tattattctc 172200 ttgatggagg acatagagac catttttagt gagtttattt ctcagtaaga agaaatccat 172260 attaaaactc ttaatttcag attatctagt tagagtctgg ctaaactgaa tcattattgc 172320 ctaattcagc tttcttggca ttattaaaat gtcacttcat tttatatctc atttttttat 172380 taatagacta attccatatt tcatttgatt gactctctgt gaagtatggg cttataatga 172440 aaacaatagg agtttccaca aagcagttta taagtatata ataccttcca gcaggctcta 172500 atcctgtcct gctaatccaa tttgtgttta agtagctcct tcatgtcaag gatggcacta 172560 ccagctcacc ttcccaagca cggatgataa aaaagactgc ctccactccc tcttatctcc 172620 tccttttcat tgttaaatgc atgaggaggt gtggggctgt ctaagccact gcttgctggg 172680 ccacagtaaa aatatgccaa gtaatgcacc gatttctgat gtaactccat gacactgggt 172740 gaggccaaga aagtaggcac tgaggaggaa gaggcatgat tccatagctg ccatttcagt 172800 tgaatggata tttaaacaat tctttaaatt tatttactat ttaagtattt aagtatttaa 172860 atgtaaatac taatcaatac ttaaataaat actgagtacc tactcaacta gttgccatgg 172920 caggcaggag ggagacaaaa atggtggcag atccccaacc tggaggagac acaagctgtt 172980 gttgagagtg gcaaaaagta aatagctatg atccaacaaa ataggtctat gagaacatat 173040 ttctttttta atcatttggt tctgagtggg gttttttgtt tttgtttttt tgagaaggag 173100 tctcgctgtt gtcgcccggg ctggagtgca atggtatgat ctcggctcac tgcaacctct 173160 gcctcctgtg ttccagcaat tctcctgcct cagcctccca agtagctggg attacaggcg 173220 cctgccacca cgcccagtta atttttgtat ttttagtaga aatggggttt caccacgttg 173280 gccaggctgg tctcaaactc ctgacctcag gtgatcctgc ctcggcctcc caaagtgcag 173340 ggattacagg cgcgagccac cgtgcctggc cagttctgag tattttttaa ttgtcattta 173400 tttggtctct tgcttgaaat ataacataca aaagagtgct tcccaaagtc tatgatgaag 173460 aaccagttta gttatccaat ccattgtgga ctgatacttt tgtaaaatac aatacaaatg 173520 aattgctata aaaattaaat gctggttggg tgacagcaat gtcaggtgct acagaagttt 173580 ctaaactgtt actctccaag gttgcactta atcatagtgg catggtaaag tttcagggac 173640 tgagactggg ccacaaacca tagcttgagt agcaaggact taaatttcca agtgtaggag 173700 agttttttgt tttttgtttt tttcaattta tctttttgtt gctgagctct agcgtagtga 173760 catggtgggt ggttagagaa atgtgatgtg aatggtgatg attctttgaa atttgtcatt 173820 ctgcttcatg accaactaca ttagccattt tttgtaactg ttccatgtgc tgaagaagaa 173880 agtatatttt ctacttacta gatgcagagt tctatatatt ttctattaga ccaagcctgt 173940 taattatgtt attcaaatat acaaatcttt accgacttct atctgcttga tgtgtcaaaa 174000 attgagagag tctagttgaa atctattctc caatagaaaa tttgccaatg tctttaggta 174060 tatacacatt tagaattact acatattcct ggcatattga ttcatctatt tctatgtact 174120 gaccatcttt atcccttata atgcattttg cttgaatgtt tatgtggtct gatcgtaata 174180 cagcaacatc aactttcctt aggttggcat ttgctcagtg taacattttc atccttttgc 174240 tttcaaagtg tccatatctt tgtattttaa ttacgtctcc tatttttaaa aaatttctat 174300 atccatgttg acaatttcac tctttttttt gagatggagt ctcgctctgt cacccaggct 174360 ggagtgcagt ggcatgatct cggctcactg caagctctgc ctcctgggtt cacgccattc 174420 tgctgcctcg gcctcccgag tagctgagac tacaggcgcc tgccaccaca cctggctaat 174480 tttttgtgtg tttatagcag agatggggtt tcaccatgtt gatggtccgg atctcctgac 174540 ctcatgatct gcccgtctcg gcctcccaaa gtgctgggat tacaggcatg agccaccatg 174600 cccagccgac aatttctctt ttaactagaa tgttaatcca ttgtcttttt tttttttttt 174660 tttgaaacgt agtctcacta tgttgcacag gctgtagtgc aatggcacga tcttggctca 174720 ctgcaacctc tgcctcccag gtttaagcga ttctcctgcc tcagcctccc aagtagctgg 174780 gaatacaggt gcctgccacc acacctggct catttttgta ttattagtag agatggggtt 174840 tcaccatgtt ggccagtctg gtctcgaact cctgacctca ggcaatccac ccgcctcggc 174900 ctcccaaagt gctgggatta caggcatgag ccactgcacc cggctaatcc attgactttt 174960 aatgtaatta ctgacgagtt tcactttaat tacaccatta tatttcataa tgttttccca 175020 cctgtttcat gtttcttttt tcatctttct ttccttttaa aatatatata tatttttaaa 175080 ttttttatta tttattttta tttatttatt tatttatttt gagacggagt ctcgctgtgt 175140 cacgcaggct ggagtgcagt ggtgcgatct tggctcactg ctagctccgc ctcctgtgtt 175200 cacgccattc tcctgcctca gcctcccaag tagctgggac tacaggcgcc caccaccatg 175260 cccagctaat tttttctatt tttagtagag atggggtttc actgtgttag ccaggatggt 175320 ctcaatctcc tgacctcgtg atctgcccgc cttggcctcc caaagtgctg ggattacagg 175380 cataagccac tgcacccagc caaatttttt attttttgag actgagtttt gctcttgttg 175440 cttgttgccc aggctggagt gcagtggcat gatctgggct cactgtaacc tctgcccccc 175500 gggttcaagc agttctcttg cctcagcctc ctgggtagct gggattacaa gtgcctgcca 175560 ccacgtctgg ctaatttttt gtctttttag tagagatggg ggtttcatca tgttggccag 175620 gctgatcttg aactcctgac ctcaggtgat ccacccgcct cggcctccca aagttcgagg 175680 attacaggtg tgatctacca tggctggcca gtttgtttat tttcttagtt cattctttcc 175740 tctcttagtt tataagttag gactgtgttt gtaattttta ttggttactc ttgaaatttt 175800 actaagcacg cttaacaatg cctaaaatta atccatatct ttcttctgga cagctcaaga 175860 accttggaaa actttaaatc cagttatttc tctcgcactg tatgcgttat ttttgctcaa 175920 tattttagtt atctctcttt aatcctatac attttatatt attgctatct acagtatttc 175980 tttatattat cttacatatt ttcccacttt ttttttgctt atcatttgtt ttgtatctca 176040 gatcttcctg gggtcagttt tctttctctt caggtgcaac tttcagaatt tccctatagc 176100 gaaagttggt tgatcataaa gtttacattt ttgttttttt tgaaaatgtc tttatggcct 176160 gggtgtggtg gctcacacct gtaatgccat tactttggta ggccaaagca ggcagatcac 176220 ctgaggtcag gagtttgaga tcagcctggc caacatggtg aaaccttatc tctactgaaa 176280 atataaacat tagctgggcg tggtggtgcg cacctgtagt cccaccctca ggaggctaag 176340 acaggagaat tgcttgaacc tcagaggtgg aggttgctgc gagccaagat cataccattg 176400 cactccagcc tgtgtgacag aacgaggctc tgtcttgggg ggaaaaaagt ttataataaa 176460 aaaaatttca aaggatgggt accttgtttt ggaacagttg actatgttct ctagagtgcc 176520 atcctactgt aaaaatggat acatttcaac aaaagtcctt ttttttccct tggtatactg 176580 aagttttact aaaatgtgac aaagtgtgga tttattactc tttttctccc tcccttcctc 176640 ccttacattt ttgcttcctt tttgcttggt ataagttgtg tttcctatat ttgtagattc 176700 atgtctttta tccattttgt aaaatttcca ttagcaattc acatatggcc tctgtttctc 176760 ctttctattc tttccttcag agatgctgag tacacgtagt tggaaacttc attctatcct 176820 ccttctctct taatatcttc tcatattttc ttcttgtttc tctgtgttac attctcagtt 176880 agttcttcat gtttaatttc cagttttcta attctgtctt caattgtgtc taatccgttt 176940 aacccatcct ctgaggtttt ttgttttttg gtttttgttt tgcttttttt ttgagacgaa 177000 gtcttgctct gtggctcagg ctggagtgca gtggcatgat ctcggctcac tgtaacctcc 177060 gcctcctggg ttcaagcaat tctcctgcct aggcctccca agtagctggg attataagca 177120 tgcaccacca cgcccagctg atttttgtat ttttagtaga gatggggttt caccatgttg 177180 gccaggctgg tctcaaactc ctgagctcag gtgatccact tgcctcggcc tcccaaagta 177240 ctggaatttc cggtgtgagc cgccatgcct gggccatcct ctgagttttt tattttaatt 177300 attatatttg ttatatctgg aagttctatt tggttcttct acatatctgc ttggtatatt 177360 atgaatctga taaattcagt actttggggt gtaatttttt ttttttgaga cggagtgttg 177420 ctctgtcacc caggccggag tgcagtggtg cgatctcagc tcactgcaag caccgcctcc 177480 tgggttcatg ccattctcct gcctcagcct ccagagtagg tgggactaca ggcgcctgcc 177540 accactcctg gctaattttt tgtattttta gtttcacctt gttaacgagg atggtcttga 177600 tctcctgacc ttatgatccg cccgcctcgg cctcccaaag tgctgggatt acaggcatga 177660 gccaccgtgc ctggccataa ataattttta atctaaagaa gagaaacttt gattaaactt 177720 tgggacactt atttactttc cctcatcaac aatcatggat tattatgtca tgattatgag 177780 tggcaaagtc ttatatgcct caagaaaaca taacattatt gagtgctatg gcattctata 177840 gagaacttca atctttggtc atagcattaa gagttcttgg tttcatagcc tcatgagccc 177900 tctttgaaat aacctatcta aatcattttt tgttgtttct gctgactctt acttatggca 177960 tgaacccata tgtatatttt attcacatca gatctgtaat gtgccaacgt tgcagcaaga 178020 tttgaaggag gtacatctca cacaatagca tgagaagtca atcatcatgc ttgtgaacca 178080 caaaaggatc atgaacccat attcattgga attaattcaa tcaattctta gatcccaaga 178140 gcttagagtg agaaggtttt cctccaaaga aaatttgtgt ttgctcctac tgaaagtcaa 178200 agatattact aatgtgggag tctcaattta ctctctctaa ccttgcagtg gtctcaaggc 178260 ttagtattct gatactaggt ctgatatagg tatttgattc cccgtgtcct tatttttctt 178320 tcacaaatca gaattcaacc tattgctttt tgttattcct ctgcttctgg aaaattctct 178380 cttttttttt tttttttttt ttttgagatg gactctcact ttgttgctca gtctggagtg 178440 cagtggctca atcttggctc actgccacct ctacctcctg ggttcaagca attctcgtgc 178500 ctcagcctcc cgagtagcta ggattacagg tgcccaccac caggcccagc taatttttgt 178560 atttttagta gagacaggtt tcaccatgtt ggccaggctg gtcttaaatt cctgacctca 178620 ggtgatccgc ccgccttggc ctcccgaagt gctgggatta taggcgtagg ccaccgtgcc 178680 cagctgaaaa ttcttttaca ttttactgag cccaaaaatg cattaaaaag tacttttgtt 178740 gaaatgtatc tatttttaca gtaggatagc acttcagaga acatggtcaa ccattccaaa 178800 acaaggtacc catcctttga catttttttt tgattttccg agacaagagt cttactctgt 178860 cgcccaggct tggggtgcaa tggtgcgatc tctgctcact gcgacctccg cctctctggt 178920 tcaagtgatt ctcctgtcct cagcctcctg agtagctggg actgcagatg tgcaccacca 178980 cacctggcta atttttgtct atttagtaga gatgaggttt caccatgttg gccaggctca 179040 tctcaaactc ctgacctcaa gtgatccacc cacgttggcc tcccaaagag ctgggattac 179100 agacttgagc caccccgcct ggcttttttt tttttttttt tttttttttt tttttttaaa 179160 gacagggtct tgctatgtca cccaggctgg aatgcagttg ttcaatcatt gctcactgca 179220 gcctcaacct cccaggctta aataatcctc ccacttcagc ctcttgagta gctgggacca 179280 caggtgtgtg ccactgtgcc tggctaattt ttttattttt attttgtaga gatgggggtc 179340 tctctatgtt gcccaggctt ggttataaac tttaaaacaa ttagtctaaa attcattctt 179400 acacattatt taaaaagcca aatagttata aagcaacccc caaccattat tgtttccccc 179460 tttccagaga caatcccttt tacctgttct ggcttattca tatgccattt tcttcaatat 179520 ttctaaataa tacatttttt ttttttgaga tggagtctcg ctctgtcacc caggctggag 179580 tgcagtggca caatctctgc tcactgcaac atctgcctcc caggttcaag cagttctttg 179640 cctcagcctc tccggtagct gggattatag gcgcccagca ccacacctgg ctaatttttt 179700 tgtattttta gtagagacag ggtttcacca tcttggccag gctggtcttg aactcctgac 179760 ctcgtgatct acccacctcg gcctcccaaa gtgctgggat tacaggcgtg agccactgcg 179820 cttggcaata atacatttct taaatttttt tttttctatt tcaggcatga tatattgact 179880 cctcactatg gagaatgagg atttatcatt cctccctctc caccttgtct ctgccacgtg 179940 tgaaccttgc ccatccccca gttgtcccaa tacaattata ttttaacttt agtaaggtta 180000 atattcagtg taaaaactat ttagagctga actatatagt aataaatgat tatctttcta 180060 tttctgccag acctattgtt ttccatggag gtggagttca taattgcctt tttttttctg 180120 gcttagcttt cctttttttt tttttttttt aattatactt taagttctag gatacatgtg 180180 cacaatatgc aggtttgtta catatgtata cctgtgccat gttggtgtgc tgcacccatt 180240 aacttgtcat ttacattagg tatatttcct aatgctttcc cttccccctc ccccaacccc 180300 acaacagacc ctggtgtgtg atgatcccct tcctgtgtcc aagtgttctc attgttcagt 180360 tcccacctat gagtgagaac atgcggtgtt tggttttttg ttcttgtgat agtttgctaa 180420 gaaagatggt ttccagcttc atccatgtcc ctacaaagga catgaactca tcctttttta 180480 tggctgcata gtattccatg gtgtatatgt gccacatttt cttaatccag tctgtcattg 180540 atggacattt gggttggttc caagtctttg ctattgtgca tagtgccaca ataaacatac 180600 gtgtacatgt gtctttgtag cagcatgatt tataatcctt taggtatata cccagtaatg 180660 ggatggctgg gtcaaatggt atttctagtt ctagatgctt gaggaatcgc cacactgtct 180720 tccacaatgg ttgaactagt ttacactccc accaacagtg taaaagtgtt cctatttctc 180780 cacatcctct ccagcacctg ttgtttcctg actttttaat gatcgccatt ctaactggtg 180840 tgagatggta tctcattgtg gttttgattt gcatttctct gatggccagt gatgatgagc 180900 attttttcat gtgtgtgttg gctgcataaa tgtcttcttt tgagaattgt ctgttcacat 180960 ccttcaccca cttgttgatg gggttgtttt tttcttgtaa atttgtttga gttcttggtg 181020 gattctggat attagccctt tgtcagatga gtagattgca aaaattttct cccattctgt 181080 aggttgcctg ttcactctga tggtagtttc ttttgctgtg cagaagctct ttaattagat 181140 cccatttgtc aattttggct tttgttgcca ttgtttttgg tgttttagac atgaagtcct 181200 tgcccatgcc tatgtcctga atggtatcgc ctaggttttc ttctagggtt ttttatggtt 181260 ttaggtctaa catttaagtc tttaatccat cttgaattaa tttttgtgta aggtataagg 181320 aagggatcca gtttcagctt tctacatatg gctagccagt tttcccagaa ctacttatta 181380 aatagggaat cctttcccca tttcttgttt ttgtcaggtt tgtcaaagaa cagatggttg 181440 tagatgtgtg gtattatttc tgagggctct gttctgttcc attggtctgt atctctgttt 181500 tgctaccagt accatgctgt tttggttact gtagccttgt agtatagttt gaagtcaggt 181560 agcgtgatac ctccagcttt gttcttttgg cttaggattg acttggcgat gcggattctt 181620 ttttggttcc atatgaactt taaagtagtt ttttccaatt ctgtgaagaa agtcattggt 181680 agcttgatgg ggatggcatt gaatctataa attaccttgg gcagtatggc cattttcacg 181740 ataagattct tcctatccat gagcatggaa tgttcttcca tttgtttgta tcctctttta 181800 tttcactgag cagtgctttg tagttctcct taaagaggtc cttcacttcc cttgtaagtt 181860 ggattcctag gtattttact ctctttgtag caattgtgaa tgagagttca ctcatgattt 181920 ggctctctgt ttgtctgtta ttggtgtata agaatgcttg tgatttttgc acattgattt 181980 tgtatcctga gactttgctg aagttgctta tcagcttaag gagattttgg gctgagacga 182040 tggagttttc taaatataca atcatgtcat ctgcaaacag ggacaatttg acttcctcat 182100 ttcctaattg agtacccttt atttctttct cctgcctgat tgccctggcc agaacttcca 182160 acactatgtt gaataggagt ggtgagagag ggcatccctg tcttgtgcca gttttcaaag 182220 ggaatgcttc cagtttttgc ccattcagta tgatactggc tgtggatttg tcataaatag 182280 ctcttattat tttgagatac atcccatcaa tacctaattt attgagagtt tttagcatga 182340 agggctgttg aattttgtca aaggcctttt ctgcatctat tgagataatc atgtggtttt 182400 tgtctttggt tctgtttata tgctggatta cctttattga tttgcatatg ttgaaccagc 182460 cttgcatccc agggatgaag cccacttgat catggtggat aagttttctg atgtgctgct 182520 ggattcagtt tgccagtatt ttattaagga tttttgcact gatgttcatc agggattttg 182580 gtctaaagtt ctatttttgt gtgtgtgtct ctgccaggct ttggtatcag gatgatgctg 182640 gcctcataaa atgagttagg gaggattctc tctttttcta ttgattggaa tagcttcaga 182700 aggaatggta ccagctcctc cttgtacctc tggtagagtt tggctgtgaa tccgtctggt 182760 cctggacttt ttttggtttg taagctatta attattgcct caatttcaga gcctgttatt 182820 ggtctattga gggattcaac ttcttcctgg tttagtcttg ggagggtgta tgtgtccagg 182880 aatttatccg tttcttctag attttctagt ttatttatgt aaagatgttt atagtattct 182940 ctgatggtag tttgtatttc tgtgggatcg gtggtgatat cccctttatc attttttatt 183000 gcgtctattt gattcttctc tcttttctta ttagtcttgc tagcggtcta tcaattttgt 183060 taatcttttc aaaaaaccag ctcgtggatt cattgatttt ttgaagggtt ttttgtgtct 183120 ctgtcttctt cagttctgct ttgatcttag ctatttcttg ccttctgcta gcttttgagt 183180 ttgtttgctc ttgcttctct agttctttta attgtgatgt tagggtgtca attttagatc 183240 tttcctgctt tctcttgtgg gcatttagtg ctataaattt ccctctacac actactttaa 183300 atgtgtccca gagattctgg tatgttgtat ctttgttctc attggtttca aagaacatct 183360 ttatttctgc cttcatttcg ttatgtaccc agtagtcatt taggagcagg ttgttcagtt 183420 tccatgtagt tgagtggttt tgagtgagtt tcttaatcct gagttctagt ttgattgcac 183480 tgtagtgtga gagacagttt gttataattt ctgttctttg acatttgctg aggagtgctt 183540 tacttccaac tatgtggtca attttggaat aagtgtgatg tggtgctgag aagaatgtat 183600 agtctgttga tttggggtgg agagttctgt agatgtctat taggtccgct tgttgcagag 183660 ctgagttcaa ttcctggata tccttgttaa ctttctgtct cgttgatctg tctaatgttg 183720 actgtggggt gttaaagtct cctattatta ttgtatggga gtctaagtct ctttgtagat 183780 ctctaaggac ttgctttatg aatctgggtg ctcctgtatt gggtgcatat atatttaaga 183840 tagttagtct tcttattaaa ttgatccctt taccattatg taatggcctt ctttgtctct 183900 tttgatcttt gttggtttaa agtctgtttt atcaaagact aggattgcaa cccctgcctt 183960 tttttgtttt ccatttgctt ggtagatctt cctccatccc tttattttga gcttatgtgt 184020 gtctctgcat gtgagatggg tctcctgaat acagcacact gatgggtctt gactctttat 184080 ccaatttgcc agtctgtgtc ttttaattgg agcatttagc ccatttacat ttaaggttaa 184140 tattgttatg tgtgaatttg atcctgtcat tatgatgtta gctggttatt ttgcctgtta 184200 gttgatgcag tttcttccta gcctcaatgg tctttacaat ttgtcatgtt tttgcagtgg 184260 ctggtaccgg ttgttccttt ccatgtttag tgcttccttc aggagctctt ttagggcagg 184320 cctggtggtg acagaatctc tcagcatttg cctgtctgta aaggatttta tttctccttc 184380 acttagtttg gaagtgaagt ttggctggat gtgaaattct gggttgaaaa ttcttttctt 184440 taagaatgtt gaatattggc ccccactcta ttctggcttg tagagttact gctgagagat 184500 ccactgttag tctgatgggt ttccctttat gggtgactct ggcttagttt tctgtcaata 184560 cccacttcat gactaattgt ctgaatctcc ccttcgcatg ttcagaagca tccagtattc 184620 tatcggttca tttcttggag aagtctctcc ctgaaccatc cagtcccttg aagtctgggc 184680 tgctggtcct tcaggcagtg gcacaactgg aatcctgaac tctcccttcc ccaccattct 184740 ggggattccc ttcacttttc ccttgtgatc agtgtcctgt tttctacatc ctatgacttt 184800 tcatttctag gtatgtttct gtgttggggt gaggcatatc cgccaatggc tcctgagaaa 184860 cggcttcctt ctgaagcata gaagcaactt atatgaacat aatctcattt tttttctaat 184920 ttggcttgta aagagtagag atctatttgg agtctaaacc aaagaattgt gatttgagga 184980 aggccttttt ttgggaatct aagttaatat tctaggatgt cacttgtggg caacttaatt 185040 tgataccagc agtctgagtt agtggaaagg gtagagggct tggcaacaga aaactcattt 185100 aaatttccca gttttgacac ttgctagcca gggaatttga gtcctgtaat ctcatgagcc 185160 tctgtttctt taatctatcc catgaggttg gtgataatga aacacacacc acccaccaca 185220 gggccagctg tgaggctcaa acagaaaagc cctttgtaaa ctctgaaatg ctacataaat 185280 agtgtctttt ttaaaaaaaa aacaaacaaa aaacagcggt gtcattttta aagagggtaa 185340 agcttagaaa atttaagaga gtgagtaatt agtatgtccc ttaaggtatc tctttaacat 185400 acaggagcat aatttgatag tcaggaactt tagagccgta ttgcttgtgc ctgtgtctgg 185460 attctgataa cattttgtcc taacaatgtg accttgggga aattaattcc acatctttgt 185520 acctccattt cctcttctgt aaaataagag taaggatggt aagagtagta ttccacccca 185580 cagaattaga ttaaaggggc ctgacatttg tgaagtgctg agagctgtgc ccagcacata 185640 taagtgctat gtgagcattt gataaatcca taaatagcca ttgtcttaac cgtgctccca 185700 aacaagtgtc tgagagcatc agttcaagtc tctggtgatt gattgcttta gaatgccaag 185760 acttactggt attgattatt accttagagt cctgactctc acagggtaat atattgggac 185820 agataggttt tctctctaaa tatcatggag tttgccaatt ttgctatttt ttaagcttcc 185880 cccctcaatg gtagacaaag aaaagactct aatgccagaa aaacgccact tttccactta 185940 agctcctata tagatttctt aacatgaggg ggctggaaac agccatctga gaaagatgtt 186000 acttattttt tttccctcca gaagccagag agaaaaataa gtcattttat tgaactgcta 186060 aacaatagat ttttactttg cattattgtg ccagatactt gagcagttct cggaagaaag 186120 ggaaaaagaa aaagtccaga gaaggcagca ccatctggct gaggacagtt cagagcaagt 186180 gggagctggg ctggaggctg gacactgagc aagacccaca cacagtgacc cttccccacc 186240 gtgggaaaca ggaatgggag ggcagctgca ggtgggctgg gattgtctgg ggagagctgg 186300 ccaccctcag tagagggggc aggggaagca cctggttgag tggggatcag agcagccgct 186360 ctcttctcag ccagctgctc cacgtggcag agtactcagg acaaccagga gggccgcctt 186420 gttgcagctg ccttcctcgg tgaaacacag aggaaggcaa atgccttcta agtggcagtc 186480 agtgctttgg caatccctcc accccacacc ccaccctacg ccccacccct ggagtttctc 186540 aactgggcca tgctctttga atgcttctcc tgccaaggcc taaaagaagg tgagtggttg 186600 tggaggcgag aacaactgga ggctgtgctg tagagaaggg agtgcagcta tgacccccac 186660 agtgagcccc ttcctaagtg cctcttcccc aaacagaaat tcctgcaagg cctcctgtag 186720 tcacctgtta gactgcagaa ccggggaggc actccatttg tcagtgtgag ttgctcagaa 186780 agaaacgccc aatatcattc aaagttattg gcttattatt agtctttatt attaatttat 186840 tagtactctt tattattatt actttaattg ccatacagat ggagggtcct ttccacctga 186900 gcatatatat tctctctact ttgtgctctc atttatactt cttcttgtgc acatgtgcat 186960 acataacaca cacacacaca cacacacaca cacacacaca aagtacgtag accttaaagc 187020 cccatttatg cttacataga cacaccgtac acatacacga atccatttgg ctaactttta 187080 aattcctcag tgctgtcact tttgttgaaa taaattagtg gagtggctag gtgtatactt 187140 cccacagcga gccagtgaac taatgtgcag ggaatgatta aatgtataca ggggcatggg 187200 gagccaactc ctcttcaata ggggtgtgaa attaggatgg gaaggctcct ctcccaggtg 187260 ccttgctttt attaaaagac ttaagagctc aggagatgtc ttcaatagga attaggatat 187320 ctgagtcttt ctggaacagt gtggaaagct gaactgtgct taggaactct gcaaggtctt 187380 tttgatcctt aaaggttctg atataaaaac ctatccaggt ttttataaaa gtagtaaagt 187440 gttttcagtc ttttattaat ctcttcatac ccttaaataa cctttcccct tttgaacagt 187500 aattgttaaa aaataaataa aaaacaacaa aaaatttttt ctcattgttt tattcttcaa 187560 accaggcatc ctcttaatgc aaggattcaa atatctctat tagggtcata atagtcagca 187620 atttccattt aatgagatca gcaaagtctc ttttcaaaga gatgcaggct ttaaattgcc 187680 agttatttct tttcctgcaa ttcctaggaa tccaattaag taagactgag tatgatctat 187740 aatgtgatat atctggctac agaaagcccg ggcctaggca ataaaacaga tctttgagct 187800 ccagctcaaa attaagatta aaaaaaaaaa aaagaaagaa aatgcagctt aaatgattca 187860 aagctttata aatgtggaaa ctgcatccat ttcctctaat atgaagtaag aaatagcttc 187920 gagactatgg tgaaaatcat taaagttact tattccaaat atagctacta attaaaatct 187980 ctccgttgga ccaggaccac aggtgatttt tacaaaataa atttaagagg ttttggtttg 188040 ctaaatctgt gactaacgaa tcaaatatgt ggccaggcgc cgtggctcat gcctgtaatc 188100 ccagcacttt gggaggccga ggcaggcaga tcacctgagg tcaggagttc gagatcagcc 188160 tggccaacat gatgaaaccc tctctgcact aaaaatacaa aaattaggtg ggcatggtgg 188220 cacacacctg taatcccagc ttctgggagg ctgaggcagg aggatcactt gaacccagga 188280 ggtggaggtt gcagtgagcc aagattgcac cactgcactc cagcgtggct gacaagagca 188340 agactccatc tcaagaaaaa agattcaagt gtatataacc actgccaaaa taaagagaag 188400 atagtgtgaa atcatgcaga gaacatgctt catatcaaaa catagtattc ttttcagttt 188460 ttaaaaattt catttgccac aatttataac agtattaaat actatatttt catttattat 188520 tattattatt attattattt tgagatggag tcatatgctg tcacccaggc tagagtgcag 188580 tggtgctgtc ttggctcacc acaacctcca ccgtctgagt tcaaccaatt ctcatgcctc 188640 agcctcccga gtagttggga ttacaggcat gtgccaccac acctggctaa tttttgtatt 188700 tttggtagag gcaggatttc accatgttgg ccaggctgat ctagaactcc tgacctcagg 188760 tgatccatct gtcttggcct cccaaagtgc tgggattata ggtgtaagcc accacaccca 188820 ggctaaatac tatgttttta ataataaatc agtgggtgta ttttaagtca taatttagta 188880 ttctgattta gagacagagt tcagcaataa tatcatactt ttgccatgta tttttaaata 188940 tatcaaagct tctcaggatg gtggtagtgg tggtttaaat cttattctgt accggctatg 189000 caggccgcat ggtgttttgc tgataacaga ggaggaaagt gtggctcgtg aggagcaaat 189060 gtcaagtcag gaattaactc aagacacagc ctgcccttct actaaaaatg tgctatttca 189120 aatatgtttt tgcaatttcc tccatgtaat gcagttgtgt tagccattta ttggtcagaa 189180 attaacctcc aaaagttaac agttgggccc tgaattctca gccaagtcta gtctaagaag 189240 cagcatattc ttgggcaagt tattgattaa ctccaggtaa ttaaaccaaa aagacttttc 189300 tagggccagg gatagtggct cacacctgta atcctagcac tttgggaggc tgaggaggga 189360 ggatcacttg aggccaggag ttcaagatca gcctgggcaa catagtgaga tcccacctct 189420 acaaaagaaa aaaaaattac ccaggcatgg tggcatgtgc ttgtggtccc agttactcag 189480 gagtctgaga tgggaagatt gcttgagccc aggatgttga gactgcagtg ggccatgatc 189540 atgccaccaa actccagcct gggtgacaga gtgagaacct gtctcaaaaa cacaaaaaac 189600 aaaaactctc cctaaacatc tgtcaaaaga gctcaaaagc ctagagagaa agatgagcca 189660 ggtgctggcc ggagataaaa ggccagcttt gtctttggtt tcccaaagac tattcaagaa 189720 ttggagggtg aattcttgga gcctccaggg gtagaagaat gaaactaagg ttgaacacca 189780 ataggcattc tgctgagcat ttcatctaag ccccctgcca ttttgcaggg gaaggctgat 189840 aacctggccc aactggtgca ggtctgcagg gcatggggca gggtggaatg ttgtcaagag 189900 tttctctttc ctagagctgt ggatggatag gtacacaggg gaaagcaaag tagagagggc 189960 cagtaagtgg aaaaaaactg ttccacatag tcagagcaaa gggagcctga agtaggtatg 190020 agagcccaaa tttgtggtca agacataaga ggattaggaa gaacagacct aggaacttct 190080 actggtcagg gccatcatgg ctccctgtgc tggcagccat gattgggctg cttcactgga 190140 gacatgctgc atgccatcag ccttcaactt tgagggccac aggtggggtg ggcactaaca 190200 catctccttc ctgggtttgg ctggaggaca gtggcctcct tgaattttgg cccattccta 190260 aactgaaggc agttccccac catagttcct tccagcctct ccccttccta agagggccag 190320 gctgtggagc tgaccatggt gctgaagatg atctgagatt gattccagag aacatttagg 190380 gagtacttcc tgtgtgctag cactatttct aagtgctctg catgggttaa ctcatttcat 190440 gttcatagca attctatgaa agaggtgcta ttattctccc cattgacaga tgacagataa 190500 ggaaagtgga atacagagag gttaacaaac ttgcccaagg tcacacagct aataagcaag 190560 gaagccaggc agagctgcac tttgatcacc acatttgcta atgaaggtta ttaacagagc 190620 cacacaaaac ctcctggatt ttcacttgtc caatatcatc ctagcagaag tgagccaagg 190680 ttccccatct caagttgcca ggcaggttgc tgtggggtgg catcttggag agtcagacac 190740 agtagtgtag actggttggg tacaagcaaa agtgggcagc ccacctactc catctagtca 190800 gtcaccacac cctaatgtta tgacttactt catacctgct tccctggtag gctcttggct 190860 ttgtgaagag ggtgccatcg tatcccccat tgcttaccag ggtgcccaag acatagtcat 190920 agtaggtatt cagcaaatat tttatgaata aatgggttac atgtgatcaa tatatggtag 190980 ctgttattaa tttgctatta tttcaacatt gatagaagca ccatgttgta gaaattatag 191040 tcccttttta ttttatattt gtcatgcccc actttgggag ttatatagag ttcagagtgc 191100 atcttagtct catatagatg catgtgtgga gacagaaatg aaagaactca agtcatgagt 191160 tgaacgattt taatgcctaa atacatgtat gactgaattt ttgttatatg ttagatttgg 191220 gatcttacag tatatttaag atttaagatc ttatagtatc tcaggaagat agttccactg 191280 acatgaaaat aactctgaac tgtctctttt agaggatgta taagcattcc atgttaacag 191340 aacttgcagt ggcagttaga aaatattcca gtcaaatttc tggttttgga gctgagttta 191400 ttgcctgttt gttgtttgat cttattcaaa tcatgttttt gttgtgttgt attaatatat 191460 aaaagatttc tgtgtctgcc atgttagctg tttgtgtgtg tgtgtgtgtg tgtgtgtgtg 191520 tgtttaaaca acactccaca gctgagctct tggaggacca ggcctatttt gacagctccc 191580 cttagtccat gtatcaccaa gctcattctc tgccaatacg ttccacgtga ttttgtggac 191640 atgtgtagca cgcctgtgca acttgcaaac acccatacat tattacaata ataattgggt 191700 tttgatgcaa ctggaactca gtactaccaa gctgccagca tttccttttg gctaccagta 191760 ctaggcagga aaattatagc ctaactgtct tcctgtttat tgataaacaa agtggccagc 191820 ccagcaatgg agcctgatta gcagtttgca ccctttgtga aaggataaac agaaccctac 191880 tgttttctgt gtttgactgc aatttgcatc tttaaagagg ttggactgcc ctgagattca 191940 tgttcaactt gagtgcctgg atgttctttg atatgttaca tgtcagcctc cttgttttcc 192000 tctccttcat cttgaaacaa tatttgccag agtttctctg ttcccatctg gcttaccata 192060 agcttcccca tagtcaccta tctgaagaag gagggaggga agaggcagga gaagaaacgt 192120 ctctgtttca ctgcgctcaa attttacatt cccagaaggc cctttaatgt catctcaatt 192180 ccattttttg aagagatagt aatataagaa tgaagaccaa aagacaaaag agaatctgct 192240 tactgctctc tttggcccat gggatcatgt ttgggctcgt tccccctcca tcatcttcac 192300 tcactcagca aaaagtgcct tccccctttg taaagtgaaa tgtggtatta gtcacctacc 192360 tcaagtttgg tgagtgttct gttctgaaat ttattctaac ctaattagat tcttaaacta 192420 aatggtaaca gagcaaatag ttggctccct ctgtaattat tttccagtga aagaaatgaa 192480 gatcatttta attggaattt gcatgatgta aaagagagta ttaatacatg taaacatcca 192540 ttaatctgtt taaacaaact ttccccttaa tccttaccgt atgtaaacaa catttgtttt 192600 gccttagaga tattgcatga ttggacccac gagactccag ttatcccact gaacagttac 192660 gttttataac ttcaaaagaa atgttatata tttattggag gttgtagggt gttaagtgta 192720 gttagacata aattgtacct cagctatttt gttaatgcca atagggatta aattagattt 192780 ttatagctgc tgtagaagtc tatttggtag ttaacaagtg ggatttttaa atcctgggaa 192840 acataatcct attataacac aggcagctga attaacataa cccaggaagg gactcttcgt 192900 ggattagcat tttttgacaa taacaaagaa aatcatcaaa ttgtgtgggg atattacatg 192960 cttttctcaa aagtaagaac agcgaattgg gaaaaggaaa cgagaaatgg ccaaacatgc 193020 tatttcttag agaccgtttc tttttaaggg aaagacagtg gaggctgggc agtaagctga 193080 ataaatgtct gctattttct gtgaagtcag taatgctttt tcagttatta ttaaactctt 193140 gaatctgaga attatagagc tggaaagaac tttgacattt atttaatttt tatagtccta 193200 ttcaaatatt tacttcaaac acttcagaaa gatggatata tctcacatat atacatatat 193260 acacatacat ataaatatat acacgtatat tgcatgatat acacacattc acacacacac 193320 acacatacac acacacttaa tagtatatga gtggcctttt taaagaagag cctttcttaa 193380 gtcttagcaa ttggttttca catgctggtg agggtgatta ttagagcttg caggacttgc 193440 caattttcat ttgcacgggt atcatcttag cagataatca catgggcatc aatcactggc 193500 atattattgt gttagataat tgcatgggca tcaatcatgt gtgtatctgg agcaagtcat 193560 catgtgggct tcaatttcat ctatctggag gaaggtaatt gtgttggaag cagggaaggg 193620 tgtgtctaca tggcagataa tcacatgggg atcaatcaca tagatatcga ggtagataat 193680 cctgtgcaga tccatcacat gtaccaaagt ggctaattac gtggatatca atcatgtcaa 193740 caccctggtt ttctggtaca ggttacacgt gaagcacaca tgttgtgtgc ctgcttatgt 193800 gggagaacag gtcagatgtc gcgtgcaccc acccaggggc ctgcagcggt gtggtgtgtg 193860 aggaagctga gccattcaga gcgtggcctt cctccacaga gcgctggaaa tgccatgatt 193920 agggatcctg ttgggattct tttattttaa ggctttggct cctgccaaaa ggaaatgttc 193980 ctgggaggaa catgactgca tgtagaagaa cgtgcagttt gtcgtcctcc cctcactggc 194040 atctattttt ccctccttca gaccttgcct cccaattcct tctcacccac atggtttggg 194100 tgtggcttca gccccagtgg agtctggggc tcagggccaa ccagtcagtg cactgcattc 194160 cactggccac catgattggt tcaggccaga ccacatgact tcagccagtc caatcagagt 194220 gaatatcagg ctttttgggg agaaatttaa gggagagttc atttctctct gaattttacc 194280 tgaggaggtg agattggcgc tgctgctgca accagtgcct gggagaggct gatatgtcca 194340 ggccccaaca aatggagcca gaaatgaagc cacctacaga aatcagatct gagaggtgga 194400 gagaaatcct gtcctgagga tactgcttgg gcctgatttc agcagtccct gaagcaaaat 194460 ccctggcctg gaaaggctca cctgagccaa tacaatccct tttggcttaa gacataattg 194520 tttggccggg tttggtagct cacgcctgta atcccagcac tttgggaggc cgaggtgggt 194580 ggatcacctg aggtcaggag ttcgaggcaa gcctggccaa catggtgaaa ctccgtctct 194640 gctaaaaata caaaaattag cctggcatgg tggcgcatgc ctttagtccc agctactcaa 194700 gaggctgagg caggagaatc gcgtgagccc aggaggcaga ggttgcagtg agccaagatt 194760 gcaccactga actccagcct gggcggcaga gtgagaccct gtctcaaatt aaaaaacaac 194820 aacaacaaaa aaaaaaaaca aaaaaaaaaa aacgtaattg ggtttctgcc cccttgcttc 194880 agaagaccct aactgatagg ataaaatcat ctgagtcttt cctgaagaac aaagtttcat 194940 aggagcagcc ccagtagggg aaggagcagc tctgagggtg taagtgaggg cagaagggga 195000 agctgaggct taaataacat caccgtcgcc cttagtatag gccttgagct gctcttggca 195060 actgtcacca ggtgcccccc ctccacacgt ccctgttgga gtgccccagt ctcctggcct 195120 ctaagcatct gagctcaagc tgtgaggaac gtttgttaaa gacttttaaa tgcaggctta 195180 atgttttccc ttttccccct gcctattctt attactttga tatttatcaa atacagtttg 195240 taatattaat tacacattaa tgttgaagtg cagttcccat caccaaaata aatgaaaaaa 195300 taggtgtcct catggcaaga accatactgt tccaaggcat tcttttattg ccatttcagt 195360 agacagttgg attttttttt tatcagcctg aatgtgacat ctgataatta ttgatttgga 195420 aagagataaa agttttggaa aagaaagtaa tagaaaaaaa agaattctcc ttgaagttaa 195480 atagactatt tcttggaaaa gcaaaatggg agtttatatg ctttgtctac caaattctgt 195540 gtggctaaca gcttgtgcct tttctccttc agtttttatt cttgttaata ctgtcacttt 195600 ctgcgtatgc taaggtttat aagaaggtaa tgtgacagtt gatagaaaca cctagtaaga 195660 aaacacggcc gggtgcagtg gctcacacct gtaatcccag gactttggga ggccgaggca 195720 ggcggatcac ctgaggtcag gagttcgaga ccagcctgac caacatggag aagccccttc 195780 tctactaaaa atacaaaatt agccaggcat ggtggcgcat gcctgtaatc ccagctactc 195840 gggagaccga ggcaggagaa tctcttgaac ctgataggcg gaggttgcag tgagccaaga 195900 tagcaccatt gcactccagc ctgggcaaca agagtgaaac tccatctcaa aaaacaaaaa 195960 aacaaaaaaa cacacatcac tgaaatttac ctagaatctt ttttttagtc cctttgggct 196020 gctgtaacaa aacactgtag attgggtggc ttaaagaaca aacatttatt tcttacagtt 196080 ctggaggctg gtacatccaa gatcaaggtg ctggccagtt cccagtgagg gctttctctt 196140 cttggtttgc aagtggctgc cttctttctg tatcctcaca tgaccaagaa agaaatcatc 196200 cccatcacat tggggattag ggcttccatg taagaatttg ggggggatat atttagtcca 196260 tagcaatctt aaaacctcat tttaatttaa taattccaaa ctcttttttg gttattattg 196320 ttaaatttca ctcaaacttt agacatagca gaatgtagca catttagttt gaaattcact 196380 tattttgggg gggtccagac tctagttgaa gttcagataa acaataggat ggctaatggg 196440 aaagggggga gctataatgc ttcactcatt cacagacctc atttcttaag tccctctcac 196500 cagtgcagta cacaagttct cacttgctgc aggtaaatat ttgtgaaatg aatgcatgta 196560 tgaatgagtg actccataaa tgactggtct ctggctggaa ggcatcccca ggactttaga 196620 tgggagtgtg agagatagac agtgtattct gcactccaag ctgcttgtgt ggtcttccct 196680 ctgcccagca tccttgggtc ttgctgggaa catcttaact catgaggcct tccaggacta 196740 ctcagactca gttatcttcc tggctgtata ttctacatgt gctatatgta ctttctgttc 196800 tgtaacatgc atcaaacctc aaatacacgt acagcgctta ccgttcacac tagactggac 196860 actctgcagg cagggattgg gtgtatattg ccagcaccca acactttccc agcatgtgcc 196920 acttcattac tcttagtgga ggtgggaatg gcatgattgt ggtggactct caagatctat 196980 cccacttctc tgtaaccaag caaatcggta actcatccaa actcaagggc taagtctgac 197040 tagaccaaca aggggtaatt cagccctcct tgccagccct gacttttcat caccagtgac 197100 agatgtggag tggccggctg aaggtttcta ggaaggtttt ctttcctctt aagagaaggc 197160 catggcaaat cagtctttcc tttctgctaa caatgacaaa aggatgtgtt gctacagtca 197220 ctaaggatag cttgccctag aacaaaggca acattgtggg ttggagagta agtagagaat 197280 gaatgggcat ccttgatgac actgctcagc tgctggcttc accagcccat cgctggatgt 197340 tgtcacataa atgtcgttag tgtttaatta agccagtctg aatttgggtt tccaatcttc 197400 cagcccaatg tatcctaact gaaaaggaac tgcagtggaa agcctatggg ctttggtgtc 197460 caatacattg gatttgattc ttcttagcag tgtgaactga cctgactttc ctaatatgtg 197520 taatggagaa agtaatactt ctcacctggg gttgatgtgt ggaacaaaga aaatatgtat 197580 gtaaaacact taccagagtg cctaaaacac aaccaatgtt gtttcttttc catttaggag 197640 atggttcact tgttgatctg gggggtccag tgggttgaat tgatcaacag tgaaatcagt 197700 aaactctctg gtcctttgca catgaactgt caggtagttc accgtctagt atgggagtca 197760 gatagacatt cgcggtcaca ctaacagtgg ggttcgactg cagtcctaac tggagaacag 197820 tgtccagcta acagaggttg agagtactga tcaaaccaca cctgaaggct ggagtgcagg 197880 tctcgtagcc atgaactaga gaacaagaaa cagcggaaga tgctgaggat gttaatactg 197940 aagaaaggac gaccagaaaa cagaaacgac ttcaaagaga aaagggagtg gaatcgttct 198000 gtgctgcttc agagggtgga gtgaggacag accccatcaa caaaggacgc aagctttcac 198060 tcaacaggag aaataactgt ctgagaatta gcagtgcaca aaggcagaga gcgagcacct 198120 catcaacaaa gcagctcccc ttcccagcag ccactcatca ggaagtcctg ctgcaggagt 198180 ttgggccaca tggcccccaa gggctcttgc aaagatctgg atttgacatt aaactgttca 198240 gcagactctt gttgtttggg ctacagcagg tggatctaga gagcttctct gttggttata 198300 ctgttgctgt tgtttttctg aattccctcc gtcttttttc tgacttcctc tcttgttggc 198360 cactataagc accacccaaa ctgacctttc acctctaact gttttttttt ccatgctccc 198420 ttgatgatca gagagatcct atacatgaag acagagtaat gggatttgtg cagctgcagt 198480 gcagttttta gggaagcgaa aggctccctg ccctgtagtc ttcctgtctc gcctgccttt 198540 atacctgaaa tgttcccttt tccctcatct ttcaactaag gcatcacctc cagaaaatac 198600 ttgataaatg tcaatatagt aactggtaag ttgttaatat atcacctgtg agggatacca 198660 tattaatgcc atatgctttt taaaaaagtg ataaaatatg cagaacatac attttaccat 198720 ttaaaccatt tttaactgta tagttcagtg gcattaagaa tattcacatt gttgtataat 198780 catcaccacc agcatctcca gaacttttca tcttccccag cagagacttt accattcaac 198840 aataactccc catttccccc tcccgtccct ggcaactccc attctgcttt ctgtctatat 198900 gaatttgtct actctagata cctcatagaa gtggaatcat gcagtatttg tccttttgtg 198960 actggcttat ttcactccgc ctattgtctt caagattcat ttgtgttata gtgtgtatca 199020 aaatgtcttt cctttttgag gctggatagt attccatggc atgtatatac cacattttgc 199080 ttatccgctt atctgtcaat agacacttgg gttctttcca ctttcggctg ttgtaaatat 199140 tgttgccatg aacatgggtg tacacgtgtc tgttcgagtc cctgctttaa ttcttttggg 199200 tatatcccca gaagtgggat tgctggatca tccggtagtt ctttgtttaa ttttttgagg 199260 aattgccgta ctgttaatag catatacttt aaaaacctat atgttaacca aggagaagaa 199320 aacaagttaa tttgaagaga gtcagaaagc gtgagtgtcc agagcctact gagccctgga 199380 agtcacggat aaaaacaaga agtgaagtca acactctcgg tgagaaaggg agcggtactg 199440 acaaacttct accatcccag tgtgcccggt tgctcccacg ccctcaggat actaaagctg 199500 ggaggaagga gggggtgggg gaggggactc agagggagag ctactgagtg cctgcaggga 199560 ttatttcgag gtgcttttgc atccattaac ttatttaatc atcaaaacaa ctcagcaggt 199620 gcccttattt ttatggacaa gtcttgtcag gtacttaaca tttttaattt ttattgcttt 199680 taaaagcaat gaagaatatc tttaagaggg aagaaataat tctgaatcca ccaagctcac 199740 acaaaattca cctcagtact gccctatttt cctttgctcc ctttgcagcc ataattttta 199800 catggttgcg ttgttgtcat ttcattttct actttttaaa ttgctacaga gatctttgta 199860 tttattattt taacagatgt atagtatgca tctaatgatt tcacttcaat tcagttaact 199920 attcccctac cattgaatat ttagattgtc ttcagttttt cactataatt ttataattgt 199980 tttataacaa gattttataa ttttagcaat aaagagtttc atgtacataa cttttttcct 200040 cttatactta tttctttaga atgcatttct aggactggaa ttaccaaatc aatgggtaca 200100 aacatttttg tgaattttgt tatacactgc tgaagtgttt tataaaaggg atgtttcaaa 200160 agtgattttt tgaagattga taatacattt tcaacagcaa tactggagta taccagtgtc 200220 tccacattaa gtattacttt taactttgtt ttattactta gtatatatat aagtatactt 200280 aattgttgcc ttaattagtt tttaaaatta attgcatggt ttccatatgc ttagtaactg 200340 tgtttcatat gtattttgtc tcattacacc ttttacccag ttatctgttg gatgacccta 200400 gaagtattgc attgtaatta agaccaaaca ccagaagcaa aggtagattc agttcttact 200460 tttgttactt ccttaatctt gggcaagtta atatttcatt ttgttaagcc tcagatttct 200520 gatctttgaa atcagaaaca accatagtac ctacttcatt agattatttc agaggtcaaa 200580 tgaggtaatg tgtctgaacc acttcagcac aatgcctggc acatggaata tgctccgtaa 200640 agattagata tcttcactgt tattatgtag agccattcgt ctgatttttc ctcctcttac 200700 catattctaa atcttctgtt gtattacctc ttacccttgg gtagttgagc tgctgggagt 200760 tggaagtaag ggcagtggag tttgttcagg gcaaggcctg ccatctggtt cacacatggg 200820 tgtgatctgg tcagactaaa cagcatttta actccagatg gctgtgtcta cattctcgtg 200880 ttatgtggac ggatgatcaa cagtggactt gcaggggtgg aaggatgtac agagacccta 200940 ttagagctac cctagtgctt ccagttagag ctggtgttca cacaagattg ttgaggtagg 201000 gctaccccat tcgcaatggt attcaaggag gaaagtagcc tcctgtctcc agccagttca 201060 accttcactg ctaattcctg tggctcctgc tgcagctgca aaccacaacc cactgatttc 201120 tcctcagata gagcaagaag gggcagaaag tccggtccac atctattcag aacttagtag 201180 ttgataggtg cgttctttat gctttctcac tgagatgtgt ctccccgcat gtgcatgact 201240 aagccacgaa ggtctgattt gacgcagaat ccactggctg gtattcagtt atccataagg 201300 attgagagcc agcacaccca tgttcctggc agcattattc actgtagcca aaaggtcgaa 201360 gcaacctagg tgcccgctca cagatgaacg ggcaaacaaa atgcggtgtc tttgttttta 201420 aaaaggaaag atcttctgat acatgctaca acatggatga accctgagaa tattacgctg 201480 agtgaaataa gccagtcaca aaaggacaaa tcctgtataa ttccacttac atgaggtact 201540 agaatcatca gattcataga gaaaggagaa agacagtttc caggggccgg gggggaagga 201600 ggaacgggga gtgtaggaag aggaaaaatg ttctggtgat ggacggtggt gatggttgca 201660 caataagata aatgtactta ctgccagtgt acactctaaa gggtttaaaa cagtaaattt 201720 tatgttaggt atgtttcacc ataataaaat attttttaaa aaggaaaaag aaaaataact 201780 tgggcctaat ctaggatatg aagaatatga gaagagttaa aagaattttt taaaaattag 201840 cagcaacttg tgagagaagg ttcctcctca aagcggagga aagaattagg atagattgta 201900 gtttagaccc aagaaaacca actctgttca aagcatatga acctgaagtt ccctgtggtc 201960 atggcaacct tgggaaggtt caggatcctc ttggtttttg tttttgtttt tgttgttgtt 202020 tgtttgtttg tttttgaaat ggggtctcac tctgtcaccc aggcttgagt gcagtggcgc 202080 aatcacagct cactgcagcg tggaccgcct gggctcaagc aattctcctg cctcagcctc 202140 ctgagtagct gggaccacag gcccacaccc ccactccagg ctcatttttt gcatttttgt 202200 agagatggag tactgctgtg ttgcccagac tggtctcaaa ctcctgggct caggcgatca 202260 gcctgcctcg gcctcccaaa gtgctgaggt tttaggtgtg agctactgtg tctggcctag 202320 gatcctcttg tagaggaacg gtcacctgag ccctttgtgc tggagaagat atctggccca 202380 taagcaactt tagtcaccgg agataatact ataatttata gacttaaaaa aaaattatag 202440 acttaaaagc agtgttgaaa tatttgaggt ttttcttgtt agattgagct tttgaaggac 202500 aagaaaatga ctgtattaaa ttcatgaata tagttttgaa agtttaaggg aatttaataa 202560 agtcgtaaat ggtgccaatt gaggtttcaa cttgtttaga tatattcaac ctgaagtaat 202620 caattttgtt tataaataga atgataacat tggaggtgga ggacaaaggc ctaaggcagg 202680 tgaatttttg aattggtaat tttaatgaat ttaatattaa cttaaaaacc aaagtaaccc 202740 acatgatctt ttccatgttg aaaagctgcc ttcatacatc aaatttcaca ttgacagctc 202800 tgatcctggt ccttcctatt ctaaagtaca gttgctgact tatttgtggg tttctcccat 202860 gagtatgtaa gctccttaag gccacaagca agttcacgtc ctgagcatct agcacagctg 202920 gacacacaca caagacactt gtcagatggc tgggggaggt ggggtggggg aaaagaaatt 202980 cttgaattta ccctggtact atatgcttgt taattgttta gacacacacc tcccagcttc 203040 ctatgacaat ttccattttg atatctattt ggacatttgc taaatgaagc catccactta 203100 ttttaatgaa ttactatatt tataataaat ataatttaac aaataaatta tggggagtat 203160 tatttatttt aatcgtcctg tagaactgta ttcaagagta tctacacaag gggtgttcag 203220 tccttgtttg cctgcataac tctcctgaac acaaaatgtt acttctggga gcctcccttc 203280 tgtgcatgac cagtgtcatg tggaagacca ccctctccga tggtgggctc aaggttctat 203340 gtctgaagtc cagaggcact tcatttggat ggcagcatca agatttcaag cttggtaata 203400 aatgaagaga gggttcccaa agtgtcttgt gaaagttggg ggaaggcatt ccccttctgt 203460 gagacagagc tgtgtcttcc tgcctggctt cctcttttgg cacctttccc ctcatggggg 203520 aatggatcct gaagcgaaga aagggatggc tgcaggcccc ttggctgtca cgctgttagc 203580 gattagctgt tttcagcaat tatgcccttc catcgagggt gtgacggctg gcgcctctgg 203640 taatgagctg ccttccaagg ctccctcccg gccttcactt gctgctctcc ttagtggcct 203700 cagagtctgc tgacattatt gccaatgtga catgttcctc ttggccaact cgggaagaca 203760 tgccagtctg ccagtgagag agcctgaagg aacttcagga gagaaacatg aagctggatg 203820 aagccaccaa gcagacttgt ccccagggaa tggggacatc agctcatcca tcccgactag 203880 ctcaaaacgc tcaagaataa cctatgccca agttttgctg gcaagtggaa atgtccattc 203940 tacattagaa tagcatagga ggattttttt attattatca catgggagtt acattgttgg 204000 tgaagtcata ctagctagat aaatgattaa ctcggtaact catcaaataa tgattgagaa 204060 accactttgt ggcaacacaa ggctatcact agaggtgaca gaggtgggga aagtaagtgt 204120 agctcctctc ctctccgggc ttatggctgg tgagacagac atacatcatt ccagtggcca 204180 ctcacatcaa tgtttggttg tgaactgtcc tatgtgatgg gaagagaaaa tacaagagag 204240 tgtaaaacag gactccaggg tggagagagg gaatccctgt ggaaatgcca tttgaactag 204300 gagctgaagg atggagagga ggtaactaga caaagtgtgg ggtacagtgg ggagtggagc 204360 agagagagag gctgtgggtg gagggggagg cacatgccaa agccgagggg tgacaagaag 204420 ctgggcactg ccaagaaact gtgagaagcg aagcttggct ggagcggcca gagcccaggg 204480 tcatgcagga tgagcctaga gaggaaggca ggggcctggt gatcctggac ttggactgca 204540 gtgaggattt tagatgtatt ctaagggtaa tggaaggcta ctaagggttt caagcagcag 204600 agatatgtgt cttgcaaaat agcattctga atgcagcaga atggatttga gctgggcagg 204660 tgtggacggg gaggccatca ccatggtcaa tgagaagagt ggagggtgat gaggaagaca 204720 gaggacatca gagactgaat tccctttcct tccttccctc cttcccctcc aaacgtagcc 204780 ctcctgtcag ctccaaaagg cagaagtggg ttctttttct tagaagacca ttccagtttt 204840 ctaagcaaaa ttccgttctc ttctccttcc taagaaagtt tacaaagaaa cagaagccta 204900 caatcccatg gcagataaaa aattttagga gagccacgtt ccggttctga aggagcaaag 204960 acctcttcca cacacacagt ggaccctgtg gtgccactct aaaacccata cctccaggcc 205020 cattagaacc cccaaagtga cctgatttcc atcaatccca aagccagcca agcaaggtta 205080 cgtttatagg actccctcct ggtgacagtc cagaaaacaa taaaaacaga tgcaagtccc 205140 actgtggtac agaagcccac tttggaaacc agggggtcaa gtgcccatta tccaggtaag 205200 caggctctcc ctaggagacc aaaaatgcat gtcaacatgc caagtggaga ggggctggaa 205260 gccacagggg ccacctggga agggaggcct cagccaggca gtaataataa aaccggacaa 205320 tgccacagag ctggcgtggc tcagccagga gccagggaag gatgggggtg ggaggaaggg 205380 cctcccttcc tccaaaatca atgtccctgt taacttgggc agaagaaaat ctgacagctc 205440 tggaaacctg cccatctgat gagaaggagg aagctgagaa gcggctggag ccagagaaag 205500 cccagaaatg gcaggcggga tcagttgccc attggggacc tggtggcagg agctctctgc 205560 attgctttta ctgacgccca ggaggacagg tgccactgcc agtccccaca cgacctccag 205620 ctgcctccta aagcagcccg cccctctgat gatcctggct ggatttgttt tatgaaaaat 205680 ccacgaaaca aacagggcac tcagcttctg aacccagttc cctgggggct attccatttt 205740 gttatctgga atataaccga ctgagaggca actggaataa ctgaaatcta cagagaaata 205800 caagtcttga caagtttcag gaaaaaccac ccttcttatt gataaagcaa taccagccaa 205860 ctagtcactg atatttattt aatgcctccc atatgaagag agtagcatga atccacaatc 205920 ctgtatccac tattccaaaa tccaaaaagc tgaaaatcaa aagttttatt attaagtttg 205980 cagccgacat attgggcagc aaagcctgac ctaaactgct gtgagactga gacttcttcc 206040 tcatagtgtg actgttccta cattttgctc caggttttgg ggaggggaga tattaaatag 206100 actgtctagg tgccatctaa ccattttaaa gtccaaaaac ttcttaagtc caaaacacat 206160 ttgtctagag ttttctaaca agggattgca cactcctatt gttatgggtt tgaggactca 206220 cagtccagta gaaaaacaag aaatcccaga gaagactcaa tagaaccctt tgcactataa 206280 atattttata gacatataga tgtttggggt tacagaatta cataattccc ttctgtgtag 206340 tctgagtaca gtttccaatg gagacagcct gcagtgagga aaacatgggt ttgggaatca 206400 gaaggtggct gggccagtat taaatgcccc tgtggccttg ggcaggactt ttctcctccc 206460 tggacctcat ccataaaatg aaagaatggg acaagatgat ttctacacac acttccggtt 206520 ttcagatttc tgtgttctat gacctcccta taggagggat aaaggaccag ggagcaagaa 206580 gctcagaaaa ggtctctttt ccacatgaag tgggaaaagg aaaagcgtaa tcacgtgctg 206640 gaccctgact ggagatggaa gtaacaccag ccggttaact ggggtgactc atgtcaccag 206700 ttatggaact actcagatcc ttgggtgctg agtgaccaat acccagcctc tggatggtag 206760 cagccctgga gacaagtggg gccaaggggg ggccctgtca tgccaaagct gtgatatcac 206820 atactgctga aattgatttg gctccatttc ctgcatacct agcagattta ccagattgtg 206880 aaaatgaatg ttttctatgc gcgtggctga tttttgcatg catctgttca ctcatctaaa 206940 ccttagttac atcctgctag gagaatgaaa ggctataatt tcttcttctt taatctggaa 207000 tagttagaaa caccatgatt tttgctttaa aattctgcac caaaatggtg aaccattttt 207060 atttttgtct caggaaaaaa aaatgaaatg atactgccgt atttttttct agatttgcaa 207120 atgatcctga ccttaatggg ggtcccatgc ctgagaacat ggcccttgga atagaaatat 207180 ccagtggaat gcaaacatga gtatctaaac atatcatttg catctgacat taataagccc 207240 tttctggctt tcacgtttcc attttagatg acagtgccgt cttcacatgt caggggtcaa 207300 gtgcaagaac agtaatacta gtatttattt agtactttgc atttctgggg tgcttttatt 207360 gcccttaatt agtaaaccac aaataatttc tgctcagtag cttggtactg caatcttcag 207420 tgttcatggg gacagtgtgc tgtagtgact aacaggatag actttggagt cagtcaaact 207480 cagatttggg ctctgcctct gccactaact tactgactaa ccacttacca cttactaact 207540 taccactaac taactgactt cagcaagctt cggtgtcttc atctgtaaaa tggggatagc 207600 gacaggcttg tcacacagag tggatatgag gattaaatca gaatatgcat gtaaaatgct 207660 taacgtaatg cctgacagta gtactgtata tatatactta tatataagtg ctccatatgc 207720 cttccctgta aactagatgt tggatacgtt gccgtccgca agtccttctg cctctgagaa 207780 tcacatcata gcccaataag ctacttaaaa tggaaaagtc cataggccat ccccgtggac 207840 caaagtcctg ccacctttct ggactctgaa ctccctctcc ctttccttct ccaactgcca 207900 aagcctcttc attcttccta cttcattttg cacagaaatt tggtttcttt cactaatcct 207960 ttccagcctt actctgaggg ctctctttcc actcacaagt ggcccaacaa ggttttgttt 208020 gttttcttgt tttaactgaa cagaagatca ttctttccac cctaagtttt tctatacaaa 208080 ttatattgaa gatgattatt acaatgacat tttcaaaaag acaattctct ccctaaagaa 208140 ttccgatacc tgcttttaaa ttgccattcc cctctcctca tggtatagat attatagttt 208200 acaacaagcc caggttcaag ggctggtaaa cccactgaaa aatcaaagaa ctcacccaag 208260 atcatgtagt cagaaacaga gactgaattc agggcatggg aacttaacct cctagagttt 208320 tcccaaaagc attgtttgcc cctttgaaca tggaaacaaa aaatagggag aagaccagac 208380 acagtggctt ataattgtaa ttcctgcact ttgggaggcc aaggcaagag gatcgcttga 208440 gcccaggagt ttgagaccgg cctgggcaac atggtgagag agatcccttc tctgcaaaaa 208500 aattaaaaaa ctagccaggc atagtagcat tcacctgtgg ccccagccac ttgggaggct 208560 gagacaggag gactgcttga acctaggagg tcaaggctgc agtaaactgt gagcacacca 208620 ctgtattcca gactgggcaa cagaacaaga ccctgtctca gaaaaaaaaa aaaaaaagga 208680 gtctgggcgt ggtggctaaa gcctataatc ccagcacttt gggaggctga ggcaggagga 208740 ttgcttgagt ccaaaagttt gagactggcc tgggcaacat agtgagacct catctctaca 208800 aaaaatcaaa aattagccca gcataatggt gcatgcctgt gggtcccagc tgctcaggaa 208860 gctgaggcag gagaatggag cccaggaggt caagactgcg gtgagccatg atcacaccac 208920 tacacttagc ttgggcaaca gattgagacc ccatctcaaa gagcaagcca gggtgggcct 208980 cttaaagcac aggtttcttg agtggtccca gaggtaacac accccacatg gtctcactct 209040 gcctctaggg gaggcacttc agaacccact gttaatcagg acaaaggatc cctccgtgga 209100 acaattctgg ggagctgcat tcccaagaac agcagattaa aaatcaaatc cgggaaagga 209160 gctaaaacct tgcgtgctgc aagatataac tcatgtgtac gtgtttgtga atggcgtgtg 209220 gggatggtgc atggggatgg tgtagatgag gggatggatg gacctatgaa aagctcagag 209280 atctatcaga gcaagcctgg gcaaaatagc gagactccat ctctaccaaa agaaaaaaat 209340 tagccagatg tagcaaaaga aaaaataaat agctgggtat ggtggcatgc acctgcagtc 209400 cagctacttg cagggctgag gacagaggat tccttgagct gaggagttca agaccacagt 209460 gggcgatgat ggcgccaccg cattccagct tgagtgacag agcaagacct tgtctctaaa 209520 aataaataaa aaattggcca ggcacggtgg ctcaggcctg taatcccaat actttgggag 209580 gccgaggcag gcggatcact tgaggccagg agttcaagac aaacatggtg aaacctcgtc 209640 tctactaaaa atacaaaaat tagccatgca tgattgtgtg cacctgtaat ctcagctact 209700 ctggaggctg aagcaggaga gtcacttgaa cccaagaggc agaggttgca gtgagccaag 209760 atcgcgccac tgcactccag cctgggtgac ggggagtgag agcctgtctc aaaaataata 209820 ataattaact aaaatttaat taaaaatttt aaaatttttt gttaaagatc tatcagcaga 209880 gcagcctggc tgcattttgt ataggtacag ttatccatac ttcaattgtt tctgaattcc 209940 agtcaaacaa cttaacatag taattatatt cgcaatgact aacttagtat ttaccaagtg 210000 cccaaatgtt caaggcattg cactggttag atttggcaga ggacagagaa atatgaaata 210060 gcaattttct ttttcacatt gtccagtcta agctctggct ataacttcta tatttggcat 210120 aaacaacagt caccagagac caataagact tggtcatttg ttctgatttg aactcatttg 210180 tttaacaaat gagaagattt aacatcaaaa tgccaacctt gggacagata tctgttttcc 210240 aagatgctga agcttaccac caaatgatat tttgatgtgc tatttaggat gtttttgctt 210300 gaaactggct ctcaatgact gtgcccttac ttttgctggt caggagcaca gtgaaattgc 210360 tctgaaaaca agcaagtgtc ttagaacccc aagaatgagg cagtagcctc gtaaaatggg 210420 ccctgctatg acctgaatgt atgtgtcacc ctcaaattca tgtgttgaaa cctcaatgtg 210480 atggtatttg gaagtggggc ctttgaggag tgattaggtc atgagatgga gcccacatga 210540 actggactag cgcccatatg aaagaggctc ctcagagctc ccttgcccct tgggccctgg 210600 gtggacacag tgagaaagtt ccatctatga accaggaagc aagtcctcac caaacaccga 210660 atttgccagt gccttgatct tggacttccc agcctccaga actgtgagaa agaaattttt 210720 attgtttata agccacccag tctatggtat tttgttatag aagcccacat ggactaaggc 210780 tcccaagaag ataaatatgc caactgtttt ctagtgcctt caggctgggg cttcatggaa 210840 gtggtgggga gcctgaacgt gcgctgcgga tagggtttta cttcctgcta cccatcaacc 210900 atgggataat gcctgacaaa gatgcgaatg accccggaaa tgtgagtgaa ggccatgtaa 210960 ttatgtaggc tttcactcct tctttctcag ccgattcagc tcttagccag attctcttgt 211020 tccatcacca ggttttatcc ctgctaactt tctttcccca ggaatgattt tcattgagat 211080 cgtagtgtgt ttcctcaaaa gaagactaga ttgtaattgg gtgtccttag atgtagaaca 211140 actctcctgt ttagatttca acatatatat ctttagcttt aatgtgtgta tgagagagag 211200 agaaaggaga ggaaaggaga cgagaggaga ggagacgaaa ggagagggga ggagagtgga 211260 ggagagggaa agtgattaag agagagaaga tgtgaaaact taagcactgg ccgggtgcag 211320 tggctcacgc ctgtaatccc agcactttgg gaggccgagg cgggcggatc acgaggtcag 211380 gagattgaga ccatcctggc taacacgaaa ccccgtctct actaaaaata caaaaactta 211440 gccgggcgtg gtggcaggtg cctgtagtcc cagctactca ggaggctgag gcaggagaat 211500 ggcgtgaacc cgggaggcag agcttgcagt gagcagagac ggcgccactg cactccagcc 211560 tgggcaacag agcgagactc tgtctcaaaa aaaaaaaaaa aaaaagaaaa gaaaaaagaa 211620 aagcactgag ctaaagtaaa gaaaaaccac tgggcaggac atggtggctc atgcctataa 211680 tcctagcact tcgggaggcc aaggcaggag gattgcttga acccaggagt ttaagaccag 211740 tctcagcaac atggtgaaac cccatatcta caaaaaaatt ttaaaattag tcgggcgtgg 211800 tggcacacac ctctagtctt agctacatgg gagtctgagg caggaggatc gcttgagcct 211860 gggaggtcaa ggctgcagta agctgtgatc acaccactgc actcagcctg ggtgacagag 211920 tgagaacttg tctcaaaagg aaggaaggaa gagaaggaag gaaggaaggg agggagggaa 211980 gaagtgacgg aagaagtgag ggaaggagga agggagaaaa aaaaaaggaa agacctggat 212040 tccaattctt gccctatttc tgatcagata tgagaactta tgtggcagag atcagtcagc 212100 tggttaccag aacccatttc ctcttcctcc tggcacacag atctacttcc acccctcctc 212160 tgcagttatc tgtcacctta ggattacact ttggctgata gcatgtgagt agaaaggatg 212220 tttactactt ctagctcctg cccacaaaac ttttcactct ctgtgttctt tctccgtcct 212280 cgggttgatt gttaatagag aaagactgtg ggagttacgg gttaaagatg ataaagccac 212340 tggcagccag gacccctgaa gatcacatgg agcagaaaac acacacacac acacacacac 212400 acacacacac acacacggac acacactgcc acactgccac tgatcagatt cgacatgaac 212460 aggaaaggca ctactattat gctaatcctc tttaattgtg gggtttctct gttacaacaa 212520 ctcatactgc tggagctgaa atgtgttgcg aagtcatttt aacctcttct gtttctatag 212580 ctgtgatgta ggatttgctt tttacaaagc ttcacttaat ccacttgaga ttgaaatgtg 212640 gtgtgtgtaa aaaagctttc cttattccat gttcttttcc agcccttccc tgggcgtttg 212700 tacttagttg cagtaacagt ttaaatataa ttttacatta gctctttttc acttagcaca 212760 ccagaagcat ttttccgcat ctccacagtc ttcataatta taaatgttaa tgactgctta 212820 atattccatc aagctgatgc actgtaattg tctaaaacaa gtgtgagatg ttgctgttat 212880 atcctgcttt gagaaaatcc aacttatcaa gacaaaaaaa ttctctacaa ggggactttt 212940 atatattgag tgccttacgt ttccaaggta taatttaaat tacacaaatt taataggcca 213000 ggcgtggtgg ctcacacctg taattccagc actttgggag gctgaggcgg gagaatcgct 213060 tgaggccagg agtttgaaac cagcctggtc aacataatat ctctacaaaa gaaaattttt 213120 taaaaaatta gccaggtatg gtagcacatg cctgtagttc cagcttctgg ggaggctgag 213180 gcaggaggat cactggagcc caggaatttg aggctacagt taactatgat tatgccactg 213240 cactccagtc tgggtgacag tgaaaccctg tctcaaaaaa aaaattaata gaccctcagt 213300 cacctactat acagagcaaa gtacttgtat tatcactggg aaaaaattta tatatatata 213360 tatatatata tatatatata tatatatata tatatatata atatttgtca gggttgtctg 213420 ggggacagaa ccaataggat atatatagat atataagagg ggatttatta tgggaattgg 213480 ctaacgtggt tagggaggct ggaaagttct gcgatctgct gtctgcaaac ggaagaccta 213540 gaaaagcagg tggtgtgatt catctgaatc caaaagcctg agaaccaggg aggccacata 213600 tgtaagtctc cagatctgaa ggccccgcag ccaggagctc tgaagtcagg aaaagataga 213660 tgccccaact caggaagagc gagaatttgt cctttgcatt ctactcacct ttttattcta 213720 tttaagccct caacagattg gatgatgcct gcccaccttg gtgagggcag atctttttta 213780 cttagtctat tgattcgaat gctaatgtct cccaaaaaca ccctcacagg tatacctagg 213840 aatgttttac cagtgatctg ggcattcctt agcccagcca agttgacaca taaaattaac 213900 catcacggat ttatacctat aaagttggac atttgcactc agtggctgct ggttgcagag 213960 aatcccagct tccctaaagc agacctcacc caggtgattt tccccaagtg tcgggccctc 214020 tccatctgtt gtcccatcta tgctgtgtct cgcggaggct gctgtgtctg tttcttagca 214080 taggatgagg gagctgacac ttctgcatga gctcagaggt caaagggcag tttgccttgt 214140 caggtggcaa ggcacctggg ctttaaggtg aacattgcac acggtccgcc caggcactga 214200 ggagtgtcta gggggcagtg agggggtcct gcactcccgt gcactcacac ttatatttgc 214260 atccattgtt tttgtacatg ctcatattta aaaatttttg tctttattgc acaaacaaga 214320 gtgaaacaat cactcagaaa cttaccatag taacagccca gcaatcaatg gactgcttcc 214380 atatactctg tttgcctacc tccccccgac tccccacccc cacccaaaga atgtctacct 214440 agctgtattt gtctgagaca gttttgtttt ctcctttggt cctgtaaccc tctgcaggga 214500 tcattgtcat gttgcttcac agtctcaatc ttaggacaag attaatattg caccatctac 214560 attctcaccg ttggagtagt cactctaaca atttgcagaa atatttaacc cagaattcac 214620 catctggatc aaaattctga caatttgcat gtgtgtgctg ggaaaaacat ttaggtttcg 214680 tgtgaactca gattagagga gcggaaggag ctcagctgtt ctccggtcgg gatggcacca 214740 tgtgttgttt aaatgtgtgc attatcgtga gcgtccatcc tgtgttatta agtgaaaatg 214800 tcttccaaga aggatcctta gcatgttgtt tcattgttta tgtacattac catacatgtt 214860 taatatggca gagaaggaaa acataaattg tgtctactac tgtacagtat cttatagtgt 214920 acaaaatgca atgagtgccc attccatgtt aaataattag gtgatttgtg ttttaaatgc 214980 tttatatgat gtagaaatac tttatgtgat gtagaaactg cttggtggaa gcaattaagc 215040 tttctaatat tatttgaggg aattgattgg ggtttccgga tgggctggga acacagtaat 215100 cttggtccta ttcctaataa tggaatacag gctcccacta tccaaactta ccattttcag 215160 gaatgggtta gatttttggt actgagggat gtctatattt atcggtatcc tcgacttggc 215220 tttgagcatc ataagatcag gaacttaatg tactcatctt tggatgccca gcacctaacc 215280 gtgcctggca tttagttggt ttaattcaca ttattctgtg actacaccaa tgaacagatg 215340 tgtcacaatt tatcaaaaat tgctcctgtt attggataaa tatacactta attttctttt 215400 ctttgttttt cttttgatgg aaaattaggc tttttgctgt ctgtgaaggg catagccaag 215460 gaattttgat gcgtgttgca aggcacacca agatactaca tatatgtggt caaagctctc 215520 ctcttctccc cagctctcac aggtctggct tagcccaatg gtattgagtc cagactcagg 215580 aggacttagt tctcttcata aaaagttgat cacctttgct ttctcctttg catgggcaat 215640 aaagaagtga aaaataaatt cccagtgagc ttgcattctg cttgggaaca acatagcaca 215700 tccattttct agagagctgt ccagtcccca tttgagggct gctagccaca tgtcaagcag 215760 gaacccagag tataaccagg aaaatgtctg tggtagaccc cagtgattca tgcctcccat 215820 ctccacaccc tcctgtagtc ccctcccacg ctgattctgg actaggccac atggcttggc 215880 cagtggaaca catgcaggct tgcacgtctg gaactctgcc acctaattta ggatcccaga 215940 ctctcctact ggagacacag gtccttagtg acagtctgca ccaccattca gacaagtcag 216000 tagggccatc ttagatcatc cagccctagt caagccacca gataactgta cccacataag 216060 tgacccctgg cgagaccagc aggagaatca tgccaatggg ccaatataca ttctgaccca 216120 cagtttcata ataaaataaa atggttgtgg ttgtaagcca ctatgtttca gagtggtttg 216180 ttacacagca ataaataact aatatagtag gcataccatc aagtccaaag taggtagaga 216240 agaatgtaaa tagcagagca aaacagcatg actggtggct gggaggctta aaactgggac 216300 aggatcagag tcatgaaaga agtcaaagaa atggttcaga agtaaggctg agactgactt 216360 acaaaagctg aaagtccctt taagttggtg tttggtgcat tggcaggggc aggtatggtg 216420 acttaaaaga gccatgctca acaagatcaa gcacaacaca atcacgggtc accccagcag 216480 accttagcga gtctagccat ttctttggtg gtggtcacag tcatgcttca gcccagtttc 216540 cacttggaca aatggtacat attttcaatg agatgaaaat taagatacaa tccatgtgct 216600 cagagagtga tcacagctct gactaaacac tgtgccccaa agtgttgagg aattgggaaa 216660 acctagctga gttagtggtc tcttttctgt tacaataaag ctcataatga aaattagcct 216720 tctttgttct tccccaagtc tttctttcta gacgaaacta ctttcaactg ttttaacttc 216780 cttactgtta acttccatat ttctagatag tatggtcaga ctgttatttc ttgactttta 216840 aatgtaagat attatctact gacttccttc tatgtaagat gaggattgag ctctcttacc 216900 cttctcccat ttcctcatcc ttccaacata aatatatttt gggattatat caacattcaa 216960 tgttacttaa agtgaccttg taaatatttt cacaactgag ccatgtttga tttgtatact 217020 tatgtttact ttactgtttt tcctgaagtt aataattgcc ttgaatttat ttatttcttt 217080 aaaaatgttt cattactcag gactgtagtt tacattacga ttctttgtgt tatacagttg 217140 atgggtttct tttctttctt aatttcttta aaaaatagag atggggtctt actatattac 217200 ccaggctggt cttgaagtcc tgggctcaag tgatcttcct gtctcagcct accaagtagc 217260 tgagactata ggtgcaaaaa agccactata cctggctagt ttacaggttt taacaaatgc 217320 attatgccac gtatccatta ttacaggatc acacaagata ttttcattac cctgaaagca 217380 tccctgtgtt ccaccaattc atcctgcctc catgagccgc tggcaaccac tgatctctat 217440 agttttgcct tttctaaaat gtcatataat tggaatcata cagtctgtag cattttcaga 217500 ctagctttta aaatttggca atatgcattt aaggttcctc cttaaatgtg aagggcatag 217560 ccaatgtggc ttgatagctc atttcttttt attggtgaat atttcattgt ctggatgttc 217620 cacagtttgt ttatccattc acctattcaa tttgcttttt ttctgtgtat ctatcactaa 217680 ttcaatactg gactctccaa cagagccgta aagtgtcttt aaatacatca agtaacctat 217740 atgttctatt tttccccaac aagttgtcat ccactgctcc atctgagccg actgcccagt 217800 aaatcgttct ggtagtttcc cattctgtca tccaggtagt ccttttgcct gatttctgag 217860 tcgggtcttt tgcttattgg atctcatgtc tttttctttc ttggtttatt ccttcatttt 217920 actggagtac atcctctagt cacttccttg gaaaagatat gggaaataat tttgtaaaaa 217980 aagatttggc aggtctgcaa gaaatattta ttttatcctc acagatcagg cttttctaga 218040 cttaaataag tcccagtaga aaaacgtcag gttgctggtg gcttggcata agcatacttc 218100 caagagattc cggaatggtt ggaattctat tatttcttct ctttttggtc taattttttc 218160 tactagcttg aaagccttct gactaatagc cccccccacc cacccccagc taatcctttt 218220 gtgaattggt ttgaattggc ctcacttcat tagttgagca tgggaaatgt taacttctgt 218280 acagagatat gtattatagc ataagaatgg ttatggtcac ttgttagtat ttctctcccc 218340 acttttggat tgaaacaatt acagaataat tagagcagag actatttctg gcaaataaaa 218400 cagttaatag ttggaaaggt atgttttagt gaagattgtt tataaacaca cctcttgctg 218460 ccaggatctt aaagtctaat taattagtat cagcccagcc tgcctctcct cttctgtcac 218520 ttgctttcat cttccttcat gtacacacac gcacactcac acgagcacac accccttgtt 218580 gtcttgcctt ttcttttcct ctttatctca gtctgcacaa gtttgcacac agaattggct 218640 tgcctcctag ctgttttgtc cccacactcc atcaaaaaat attttctgca tctctaattt 218700 catcaagata tgcctgactg agaatgtcaa aaccactgag cagaagtgtt taatccaaag 218760 ttggctccgc cggtgatgat cagctgagga aacaacctcg aatttttccc tcattatttg 218820 ttaggatgtc agtttttcac tttatggaat aggttcacat cctgcttctc accccctgcc 218880 ccccactctt cattgggcag aggcctccca ctgatttcca atagagctct ctgcacccaa 218940 gaaagacaca tggagaagaa atggtacctg gccgtctgtg ggtatgccac cttcaacaaa 219000 gatgtccata agcagacagt cacttcatgg tttcttggac aggcagatcc tggccatgtt 219060 catgtaattc cataaggtaa ggctggagag gctgagctgc ccacttaaca agcaacaagc 219120 cctgggggag tctgggcagc ccaaggtaga actaggggtg gaagatcctt gcttggccct 219180 cggatggctg tacgacgtca ggacaggctg ttaacccctc tgagcctcag tgccgtcctc 219240 tgtaaaatgg gaataatatc agctacctcc tagggttgct acaaggataa aaaccaagta 219300 agtgcgtgtg aatgcccttt atcatgaatg agaaggtgcc ctgtaaatgt tgcttattag 219360 ctgaccttag agataagaat caaaatgaca cacttttgtt ccaggtagtt tttccccttt 219420 ggcttagtcc ccttttttat gagggatgat ctgctgttta aagcatttat taatataaag 219480 attatgaagg gaaggattta gaatgtaatt agtggggaag ggggcctgct tctctgggat 219540 gagaacgcca tgacttgttg gctcagtaca gcacactggt aatcttgttt cctgaggctc 219600 tgcacacgct gagagcacat cgtgctcaca ggcacactta gtgaatatct gagaatgtgg 219660 tgagggagaa cgtgtgtcag gaactgggca ggtgggcggc acagattgcc attcctgcac 219720 tggccgtgat tgtagtaagt ccctcatgga cactggtaga acccgaatag acatcatcaa 219780 atggatgggt cttcctgccc gctgtttcag tttgcctccc agtcccctct ctgcccacca 219840 tccgcacaag ttgcagaatc tgcagcctca ccccactgga caaagggcta cagatctgcc 219900 agtatatcgt aactcacatg gtaggcagtg gcttatggga tctttctaga agggagaagg 219960 ccagactctt cagggcctga aggcctgtat ttaaatttct tcacagtttg gaagaaagct 220020 actgtgatgg tcaattttaa gtgtcaactt agataggcta tagtacccgg ttatttaatc 220080 aaacactaga tgtttgatta aaaggaaggt attttgtgag tgtggtcaac actacagtca 220140 gttgatttat gtataggtgg ttgccctcca taaggtgagt gggcttcctc tgattagttg 220200 aaggtcctac aagcaaaact ggggtttcct ggaaaggaaa atctgcctca gaaccatgac 220260 atcaatgcct acctgagttt tcagcctgcc agcttgtcct gcagatttca gacttgtcaa 220320 tccacagtct catgagccaa ttacttaaaa taagtctatc tatgtatctg tgtatctctt 220380 atggatcctg tttctctgga cagccctgac tgatacagct gctctctatc cagagattac 220440 ctttttcttt gactctattg caatccaact ctcagcagtc cagaaaatga aacattttct 220500 tttcactagg aaaaccaact gtgttactgg aacaacaaac caggcaaatg aatcccaaat 220560 catagtccaa ctctgatctt gaaatctact aagctttgat aaaactaaga tacatatttt 220620 atcttttaaa aatcttgatc cattttacct catcagaagt ggggagttca aatcatctgc 220680 attctaatcc catatctgtc ttggttctca tcactgttca gcctctcctt actccctgag 220740 atgctcgccc tgttggaaca catgcccctt ggcgaggaat ctccatacac caccgagctg 220800 gagttgtctc ggggcccgag gcagtgggac tcacgttgta agctttaggt gtcaatgaag 220860 gtgtctttcc ttgaaagaca ctaaaacttg aaaaagttgt catctcataa ttccaggtgc 220920 caagatcact caggagagaa atgctcctcc ctgtttaagt tattattttt atctccaggg 220980 tcatttctgg aacccttcat atacatttta atcactttaa gtctgaatca caaacattac 221040 aaggctcacc tttggccatt cccaggcaga tgaggcaggg tctgggttcc gtgagtcatt 221100 taccacagac tccagttgga agcagttccc agtggggtta cgtgtgagcc ttttcaattg 221160 tccgtgactg tgttccgtat acacatatcg attcccctct ctaattccca gagctagtgc 221220 cctgcccttc tgtctggctt gggtggagcc cctgaggggt ggggaaagga cctggcgcca 221280 ctgagcagac gtcccttaat ggtaatcctc cagtgagtca atggcctcca aagagaccat 221340 gagcgtggtc ttgttgatga ggaatgtagt cacagtcaca caaaaaagtc cccagtctct 221400 gcctcaggac cccatgcatg gcccatcatc cccgctgcag aaagaaactg gacaggacct 221460 ccccttagga gcctgtcagc ccttgtcagt aatcagccca ggggctactc agaatgactg 221520 gaggcactca catccacccc ctaccaacca cactgcccgc tctcagcccc tgccacctgg 221580 ggagccccac accagggcag ggcaatcaag cttggcttct gcatgccgtg caaagcttgc 221640 cagcagccaa gctcttgaaa tatttatatt tatacatgca aggctcagac tctcgctttg 221700 tcccgacagg cgccatcgta tgtggggatg gggtatggtt cgggagggtt cattcatccc 221760 atgctagcgt gcctacccgc caaggctcac ttgcgcagag gaggagggat ctcaccagaa 221820 tagtcaaaaa gttggccatt gtcatgaatc aaatccatgt gttggaagaa atatacatta 221880 gaaaattgca tagtctcccc ttccctttga ttcagagatt ttcgtttcat ttgtgcacag 221940 ggaagagttg aaatgcccct cctgaggggt gcccttctgg ggatgcagga cccacggatt 222000 gcagggtgta caaacacaat atatgtattt attttcaaag acaacatgaa ataacaccat 222060 agagtttttg tggctacctg ttctcttttg aagaactgtt caaaaactag atgatgggca 222120 aaaactctat agaggggaaa ggaggcagga agagccacag tttcagctaa gtcagacggg 222180 tgcactcgag actcaattag caattgttcc catatatttc aacacacaca ccttaaacac 222240 aggttttctg agtgaagtca gtgatgaaag cctgtgggtt aggggaattt tcccatggta 222300 gcgacagctg ttcccacaga aacagctcaa tttatctcag agatgaaggt ttcactagct 222360 tgggcctctc atcaaattgc atgcatggga attattttta agcactctaa aatggtatca 222420 tttcctagtg gcaaattatt tgggtgtatt ttgaaactaa ttaaaaggga aatgtcctat 222480 tttgtaaaga gcagcatttc tacattttaa aaatcagatg ttctcagtgg ggagcagggt 222540 tttctcttcg tcagtgttgg ctattgctaa gtgcgtccca gattgaaaac ctaaatgaaa 222600 taactacaag gaaaggcatg gggtaagctt atgttggaaa aggtggaggg agacacacat 222660 atataataca tacaccattt atctgggaat ttagaaagcc ttttcatgtc atcttttttt 222720 ctttcttgct cattgcttgt tatttcactg tgagccttgc aaatatggag ggcggcagag 222780 gtgccaggct ccatcacggt gtccaaaaat tggctttgta catatgctga attagagatt 222840 ggctggcaga agcagtgtgc agaccctaga ttggcaggga ttcctcgtga cggaagacag 222900 ggctatgaac ccacgggatg tactctgaag ccagcagcca tgcaacgtgc tgcatcccca 222960 catgccaaaa cctgttttca aatacattca gaatctgcat caggcatcag atcccaccca 223020 ggtaacgccc tccaaaactc gaatcccctt tcctttctca tgaggaaggg aatgtgttga 223080 acctgtcaca ggacagagat ttgaaatttt tcacccaagg ctccaggtca ttttagtcac 223140 cacctcttgt gaataggcac cgtagcatcc aaggaggaag gtaggaatct tgcagatgca 223200 aaccttcctg ttttttttct tccttggaaa taagcaaact gccaaggcgg ttctgatgca 223260 ggaagaatga atgcagtgaa ggaacacgtt aagacagccg gagcagggaa gtccatgcca 223320 aaaagatccg ccatctgggg cttttttctc actgtgtcaa ccagaaaatg cctctctcat 223380 gtacaagtag ctagttggtg gctttactct tcccaagaga tctactttat tttatgggca 223440 atgatgagtt ttaataaaag cagggttgtt gttgttgttg tcattactga tcttgggttt 223500 ctggtttatc ttagaattga gcactagaaa ggaagtgagg agaattattt tctagaccaa 223560 taggtgcttt tgactcaaat gatgacattg gacacttcta ggaaccttta aagtagggac 223620 attagctcca gttacgtcac ctttcctcta agggtacagt gaaggatcag gagctgaaca 223680 agctgacctc agtcccaatc aactccgaaa tgtgacagct gattagagcc ttgcagcctt 223740 tcaggtactg tttaatcatt tactcgcttg agtgtataag ctccgtgaga gcggagagcc 223800 tgtctgccca tagcacacac tcaggaaata ttgttgaata tgatcattgg gttgatggtc 223860 tcacggggtg gcaccaaggg ggccagcatg tcaagcgtaa ttcacaccgg agcaagcttt 223920 gggtcacatt ctgaatcata tgtgatgtag tgaacaagct ctcggatggg cttcagggga 223980 tgtgcgttca agtcctggct ctccccccgg catcagagtg accttcagtc atttgttgat 224040 ctctctctcg gacttttgtc tccttgtttc taaaatgact agataattgt agagctttct 224100 tcagccctaa aattctgtga ttctgaaact cagccagtca tctaaaaatg cattttctgc 224160 atgatgaaag atatttatta ggcctaagtg gaagagccag cattcttgat gaaaagaatt 224220 actctatgca cacatcctaa ggacagtggt ttagatcagt gccctcctgg tagagatgaa 224280 caacacaacg ggaaggacag gcactgacgc acataaagat gaggaggctg agcgtggttc 224340 caggcaccac tgcggtatag aaagtggcac ctagagccag ccaaggacat aaagatggac 224400 ttggagacac tggagcagtg tgggtgcccc tcagcccagg aatgttgcag agaggagtca 224460 tatgtgagat tagggttgcc ccaagttacc tctaagttct gtccaactca actactctgt 224520 gagtctgtga cagtccctag ctctgtgtcc taggacacag tgacacccct agagatctta 224580 ccaaagacct caaatagtcc aggcactgtt cctcttaagg gatgtagaga ggagagggag 224640 agatggaaaa gggagaactc acctttgtta acatactgct ttctaataac tcttttaaag 224700 aagtgttcat tccattgttc atggaatatg cttccagtcg tggattgcat tgaaaagata 224760 agtccatgtc ctaatccctg ggacctgtga atgtgacctt atttggaaaa atggtctttg 224820 ccgatgaagt taaggatctc gagaaaagac catcatggat tatctgggtg ggcccaaaat 224880 ccaatgacaa gtgtcttttt aagagaaatc agagacacac agaggagaag acagacacag 224940 aagagaagtc agacacagaa gagaagtcag acacagagga gaagacagac acagaggaga 225000 agggcacatg aaggaagagg caggggttgg gtggcggcag ctgcagggac tgccagcagc 225060 cagcaggagc tgcaggaggc aaggaggatc cgctagagag ggactgcgcc ctgcacacac 225120 ctcaagtcca catttctggg ctccagaact atgaaagaat acatttttgt tgttttaagc 225180 tgccaatttt atggtcattt gttatggtgg ccctaagaaa ctaatacacc tcagatatat 225240 tatcattgat accattaatc aggagctgca aggtctcttt tcctaattaa catcatggtt 225300 gttcttacta ataataagaa taaaagaact ctcagggagg caggtggagg gagagcatca 225360 ggataaatag ctaatgcatg ctgggcctaa tacctaggtg atgggttgat aggtgcggca 225420 aaccaccttg gcacatgttt acctatgcaa caaacctgca catatatccc ggaacttaaa 225480 ataaaattta aaaaatgaac aaataaataa ataaataaaa taactctatc ttaaaacaca 225540 ttaacaatat tattgaagaa taatattaga tcttttgaag taagcatttt tttttgcccg 225600 tgtaatagct gtctgtaaat acccgcttct tgagtgaacc accattttct ttcttttttt 225660 tttttttgta gaaggaaaca cacgctacca gaaaaaaagg ggccccattt tgatatccct 225720 ccatccctgg ccttgttttg gtaactttgt ttctgtacca gatccacact caatcaacct 225780 gtctggttta gggtattttt agcttcatag agcaatagta tcaatacaat tctgctgttt 225840 tattatacat ttatcaaaca gttcactatc tggtcttttg gccagaattt cttggcctct 225900 tctcagagct ctgtctcaat agatcttttg ataactgttt tccaacacag tcttcatttc 225960 aatgttagaa tatgatgtta atgaatttac tagcttccag tcgaggatga atagcttaca 226020 gtgtttgcgg caatattgga tgtatttatt tccaagggaa tgatttttaa cagcacattg 226080 tgttcttatt tgcttttcac aatccagttc cagcatctga gaaactttgc tttgatggtt 226140 gactcccatt agggaaacac tgaaaacaat tatcctgtag tggtctcggt tcttcctggc 226200 agctttgcat ttccatggtg cgagaccact gggtcgtacc acttgtttct ccctccacgt 226260 cctcaaatga tctcttaaaa gaacccactt tagacctcat tgttaccttc cctctacttc 226320 tttttcttct tattgaattc aattcaacaa catgtattaa atacttacaa cctggtaccc 226380 aggtagaaga agccaacgta tagacagggc atgtcattgg atagtgataa gatctgatgg 226440 ggtgagtatc taggcaactt agactgggtg tggggttgaa ccagcatatt taaatttatg 226500 taaaaactga gaaacaccct gaaaaggact tttattgttg gacataattc tctagtcctg 226560 aagttatcat tcaagggagt tcaagaactc atcccttaag tggactgggc aagctggcca 226620 tttaccactt gtcacagtta gaattaggaa cttggctttc atattatcca ttggtgtcac 226680 agagtgggag gaaaacatca gtaatggatc cataggacca ccagtggagg caaattgaat 226740 ttgggatatg ttatatcaaa tctgttaaag ggaaaaaaaa gaaagaaaag gaggggagag 226800 aaggaagaaa agaaaaaata aaagaaaaaa acccaaaaga attcattata taaccattat 226860 atgttaatgg tacagtttaa gagattttga agtattgtca tatatcattt cattaagtag 226920 tatatacata catacataca tatatatata tatatatata tatttttttt tttttttttt 226980 tttttttttt gagatggagt ttcgctcttt ttgcccaggc tggagtacaa tggcacgatc 227040 ttagctcact gcaacctcca cctcccaggt tcaagcgatt ctcctgcctc agcctcccaa 227100 gtagctggga ttacaggcac ctgccaccac acctggctaa ttttttgtat ttttagtaga 227160 gacggggttt caccatgttg gccaggatgg tctcgatctc ttgacttcat gatccagcta 227220 cctcagcctt ccaaagtgct gggattacag gcatgagcca ctgtgcccgg ccagtagttt 227280 atatttttat tccaccaatt cttattctta aaggaaagaa ggattaaata agccctaaat 227340 gttatattac attagaatct ttgaattgct gccatagcta cataatggtg tggaaagtag 227400 taaacccatt tttcccaact tatgggaaag tacaaactaa aaatgagtga atgaattaat 227460 gcataaataa gtcattagaa ctctgccatc agagtcctcc agtcacctcc cccaacacat 227520 actcaaagac agaaccatcc ctgagtgcct aggtatttgg cactgccaga gcccctgagc 227580 accaaatgtg acaggaagcg gggttaccgt gttgcttttt tttttttttt tttttttttt 227640 tagatggagt ctcactctgt cgccaggcta gagtgcagtg gcgcaatctc ggctcactgc 227700 aacctccaac tccctggttc aagtgcctgg ttcaagtgag tctccttcct cagcctcccg 227760 aatagctggg attcaggcac acaccaccac acccagctaa tttttgaatt tttagtagag 227820 atggggtttc actgtgttgg ccaggatggt ctcggtctcc tgatatcgtg atctgcccac 227880 ctcagcctgc caaagtgctg ggattacagg tgtgagtcac catgcgcagc cctgtgttgc 227940 ttattttgag gacacctggg cacttccagc cctgcctcct tggaagtggg agggataact 228000 ggcgagagag gtgggcatgg ctgagcatgc agtgggaggc agaacaaagc cagagtccca 228060 caggtaacct tctggccagt gcctggttca cgcagcttta aggtgctcca agaggactgg 228120 gagacccctc aggaccacgg gagccttggg agaaaataaa gtaatgcctg ccaaggtgcc 228180 aagccagtgt caagcaggtg ggcccaggaa gtaactcagt ctcaacctgc ttatgccagg 228240 actcctggtg agcccacagc ctgggagggc atacgagtag gtcctgtccc ataatagatt 228300 actcagtcct gactcatata gggggcttat gagagaagga atcctaaggc cttcccaggt 228360 ggcctgcagg agcctcaaag tcagcattgc agggaacact cattccccct tcctgaagtt 228420 tctttccttc aggagggagc tccactggtg cagtgctgtg gttctcccac cccagcccac 228480 atctccgcag agccagggtg atgcacccag tggctatcct ggcatatgta gctctgcctc 228540 ctcctttttc cttcctcgag ggtgtgggct gcccacaggc agtgtgactg attccctgct 228600 ccccggggcc cactctctgc cacacaggat gttctcggtc ctctgcagcc tgatgataag 228660 tcagtctaac tctatggccc agtattaaaa gaccatgtgg ctctttcact cacttctgtc 228720 ctcaacccag cctttatcag aaatgaagga aatgttctaa ttctcctcct gctgacactt 228780 ttgtcttatt gttcaattgg ttcagaattt tgacggtcaa gaggtgatgt gatcgagatc 228840 ctaagcaaac acctctaaac taaaacaatc atgtacactt acccccaaat tctacctatt 228900 gttcttccct ctattgttgg aacacacctc cctcttccta acacacacag tgagaaaggg 228960 aattctccaa gatcagtaaa aagattgcca agtagtgcca aagcccagag cctgtctctc 229020 tgtggttacc tctttccaga tgcttttctt gctcctgcca ctactctgtt ctcaccgtcg 229080 cctctaccct ctatgagcgg ctgattcatc tctgcttttg tgtcagcgtg caggctaagc 229140 tgctacaaca gaaaagacac aaagcaacag cagctcaaac caaatgaagt ttatttctct 229200 ctcacccaac agcacagaaa gaggtagccg ggtggtccaa ggcaggtggg aagtgctcct 229260 cctccatgtt cattcagaga cccacgttgc gtctgccctg ttgctctgac atcctcatct 229320 gcatggctga tgccggctca ccctaccatg tttgagttcc agcatcggag atggaggaag 229380 agagagtgga gggcaggtgg cttcctttta agggttaaat gttgcctaca ccacttctgt 229440 tccattcgca tgctagctgc aagtgggtct gggatatgca ggctttaaga agtgccaaaa 229500 ctcaaaggaa aaggaagaat ggttgctgtg agccatcagc tgtctctgcc acacccctgt 229560 gcaaccacat gtgatatctg cacatcaccc tgcactgcat ttttgcattg ctctttattg 229620 catttttgca tccccaggac ctagaacagt gcctaacaca gctgagtagt tgaacagctg 229680 agtgaatgat gaaggccttt ttcccccagc aagccaaatc ccagacccag gtaagagtaa 229740 aacagaacta acagagacaa gacttgagga tgctgtgaag gtatcactgt gcacagttaa 229800 ccaggaagtc cagggtaggt ggtagattgg caagaaaatc tgacagtgag ctgaccgccc 229860 aggggccagg acttggaaga caggggaagg taaaccagat gacaacgaca aggggcagct 229920 cagggaggag ctgtcattag agaggtggat ttcagggctt gagagttcgg gatgaggcaa 229980 ttttgagaaa agtgaggcca aagtatgacc aagtcctcag ggtgggtgtt ggggaacatg 230040 cagtcatgag atgggatttc tcctggcgct gcttggagaa gcttccagcc gtgagtatga 230100 gggggacttg aaagggtgac acagtcagac agtgtggact ctgccagggg gagcgttggt 230160 tggtgaggcg aaggaggaca gagacgcaga tctagaagat gtctccctct acccctggcc 230220 ctgcatacag gggagtgagg cgtttcttcc cctggagagg gtggtgacac aaagcaggac 230280 aaagccaagc ctcagttcca gcacacagag tggacagtgt tccagggagt ggctgcttat 230340 gtgagggaat ttgtaacctt ccagaagcta cagtgcagta aggtaggagg tagggccagg 230400 aggaaatagg cccgcaccaa atgcaggtgt atgaagaatg gacttaacca ttgtcacagt 230460 gtctagtaac taccgattca gaggacaaag tcccagtttc agggctctgc atggtgatgc 230520 cacggtgcca cagtgtgatg gattacaggg atctgttaaa atacttatat gcactttcct 230580 atgtttaagc tttttctata aaaagtatat attgctttta tagtcagaaa acaatgccac 230640 ttaaatcatt aaattcttcc aagatggtgg tgctagagag attatttcat ttctgtggtc 230700 cttgcttagc tgtaaaagga gagttggaac caaacaccgc atgttctcac tcataggtgg 230760 gaattgaaca atgagaacac atgaacacag gaaggggaac atcacacacc ggggactgtt 230820 gtggggtggg ggaaggggga gggatagcat taggagatac acctaatgct aaatgacaag 230880 ttaatgggtg cagcacacca acatggcaca tgtatacata tgtaacaaac ctgcacgttg 230940 tgcacatgta ccctaaaact taaagtataa taattaaaaa aaaaaggaga gttggcctca 231000 gaggtcccca cttaatgcat atcattgtct tcctgctcag ctctcatagg attcttgcct 231060 tcagtgcaca ggtgggaact ggaaaaataa gggtcagggc caggtgtggt ggctcacatc 231120 tgtaatccca gcactctggg aggccaagac aggaggatcg cttgagccca ggagtttgcg 231180 accagcctgg gcaacacagt gagatcctgt ctatacaaaa agtaaagaaa aattaaccag 231240 gtatggtggc acacacctgt accctcaact aattgtgggg gtgaggtggg tggatcgttt 231300 gggcctggaa agttgaagct gcagtgagca ccgtaattgc atcactgcac tccagcctgg 231360 gtgacagagc gagaccctgt ctcgaaaata aaataaaatg tttaaaaaac agtcatgata 231420 taggtcacca accaagagca gaaattatca tgatttcaag ttgctttagc cacaatattt 231480 gccagtagtg ttgcaagtag aaatgtcacc tagtaaaatg gagctacctc gtggagatct 231540 gtgtgatggg aaaatgctct gtgaggattc atggcacgtg ctcaaggggc tgctgagttc 231600 ctcttctcag gcaggtcttt cttctctgtg ctttgggcac tgtttgccca ataggcgagg 231660 catttatgtg tgcaccagcg cagcagcttt tcaaccctgg ccgtccagca gggtcacaag 231720 gggagccttt agaagcacgt gtccgagccc caccacacac ccatcaaacc aaataaagtg 231780 gatatcccca agaagagtgg agacagaaat ctctacatac caaaacgtgt actaagcttc 231840 ttaaccataa atgagaaaca tttttgtaaa ttacaaatat tattttttac atgatatctc 231900 tggttttccc tcctctctgt caagtggttt taagttctca aaatcccaat gcttttatat 231960 ctgtgaatgc ttcttgaata cagtttaaaa atgatagttt ttatctattc ttcaaatatg 232020 cataagtaat tatatattag atgtatttat aaaggtaaat attaagtttc agctaacttt 232080 ttaaaacata atttttatca aaaatgacaa agattgaaag cttttatatt taaaactaag 232140 ggatactcaa aacattagat attttgcatt ttcctaccat aagatgcata gtaagttgac 232200 atattaggcc agcaatatgt tatttttatt caaaaagaag taacaaaagt gagtatctct 232260 actgtttgga ggaggggggt tctttcgaga taactgatca gaggagggtt atacagagaa 232320 tgttggatgt taaagccaga aagaacctta gagtttatct tgcatttgta gaaactgagg 232380 ccccgatgcc tacaattttt atctcagaaa tgccaccgtg tgtggcatat ttttcaaggc 232440 acataaaaat gggttgctga aaaattctca atccatgtat tgtttttcag cttcagaaga 232500 atgctaacac tgacttttgt taaatgctgt aatcttccca tattactata aattgtcaaa 232560 catttcacat tctttttctt tttttgaaac ggagtctcat gctgtcaccc aggctggagt 232620 gcagtggcgc aatcttggct cactgcaagc tccgcctccc aggttcacgc cattctcctg 232680 cctcagcctc ccgagtagct gggactacag gtgtccgcca ccacgcctgg ctaatttttt 232740 gtgtgtgttt ttagtagaga cagggtttca ctgtgttagc cagtatggtc tcaatctcct 232800 gacctcgtga tccacccgcc tcggcctccc aaagtgctgg gattacaggc gtgaaccacg 232860 gcgcctggcc tacatttcac attcttaaaa gccttttgga aaactgagca actggtatta 232920 agaatggtta gatttgagaa gactacccta aagaccatat tgttaagcat attgagcaga 232980 tgaagagtta catttgtaat caactaaacc tttttatcaa tctccatgtg agtcaacagt 233040 gtagccagcc agccaggaat taatgcactt acaggtgggg catagcatct ggaagagcag 233100 tgggagcgcc tgctcagagt ttagaagggg catcaccaaa cctgggtatg tccagagcag 233160 ggcaactcaa gagggcagag gatgttgaaa gtgtatcaga gggtttcaga gagacaatga 233220 tcagaactag gagggttcga agacagaaga cccagggaaa catacggacc acacttacat 233280 atctgaaggt ccatccagtg gctgtgttta cacagaaaca gatcatcagt tgccaagagg 233340 atggcagggc tcttgccttg gccagagctc ctgaggtaac tatgaagact cttcccaact 233400 ccaagactct gattctgtga ttctcactcc aggacctaac ctgctgatga tgtttacaaa 233460 atacaagaaa gaatcctagc tatacgaatc tgacagacat gaggaaataa tgcttcgtgt 233520 gtgtgtgtga cacaccattg ggtgtgtgta tgggtgacag agagacagaa cagagtggtg 233580 gggaggggca tggaatttta aaagattaat cttttaaaaa ttttttgtgg gtacatagta 233640 ggtatatata tatttatggg gtacatgaga tactttgatt caggcatgca aaaagcagta 233700 atcacatcac ggaaaatggg gtatccatct ccttcaagcc tttatccttt gtattacaaa 233760 caatccagtt atacccttct agttattttt aaatgtgcaa ttaaaaatag ttaccctgct 233820 gtgctatcaa atacttggtc ttattcattc atattttttt ttgtactcat taaccaaccc 233880 cacttcccca cccacccacc cgcactcccc acaccccttc ccagcctctg gtaaccatcc 233940 ttctattctc tatcttacaa gcatatagtt cccaggaagg gtagctactc tgtgccccac 234000 cccacgctgg gaactctgag ggcttcaaac acagtcccaa cctcaatgtc tgtctcatct 234060 atctggttat agagacaaga ctaacaaccc tgcgatggtc agagacacca ggagacctcg 234120 ggaactctgt ccttgtggtc ctcatccctt cattctcctc ctgagccctt actctccttt 234180 ccttaaaaaa aaaaaaaatc actatataca attcacccat cttaatcata accacctcca 234240 ttcaaaaagg ttacatatgc aggccaggca cggtggctca tgcgtgtaat cccaatactt 234300 tgggaggctg aggtgggagg atcactgggg gccaagagtt caagaccagc ctgggcaaca 234360 tagcgacagc ctgtctctat taaaaataaa tttaacaaaa accaaaaggc cagatgcagt 234420 ggctcacacc tgtaatccca gcactttggg aggttgaggc aggggaattg cttgggcaca 234480 agagttagag accagcctag gcaatatggc gaaaacctgt ctctacaaaa aattagccag 234540 gcgtgggggc atgcgcctgt agtcccagct acctggaagg ctgaagtgga aggatcactt 234600 gagcccagga ggtcaaggct gcagtgagct gtgatcgtac cactgcactc cagtctgggt 234660 gacagagtga gacccttgtc tcaaaaaaaa aaaaaaaaaa aaaaaaaaaa aagggttaca 234720 tatgcatatg aaaaaaggca gaaaaccgta ttccctactg ccttcttagt taaacagtac 234780 caaggtagtg tttgttgccc aaacatatta aatatggctt atgaagtcag cttacacgca 234840 gtccagattt acatcctttt aaaatcattt ctctcaccta aaccataaca gcagcagatg 234900 gacagaggaa gaaatggaat gtggtcacat tccatactaa tattatgaag tactttcaca 234960 ctgcaatgag taaaggacca tctgcaacct atagcctgtg tttctgctga gaaactgatt 235020 ccggacttaa ggtttctaat ttggaacaaa agcactgagc aggttgctct ttgtaatttt 235080 ttatcgagag gtggagagca tactaggcct acctggattc ctgaagaatt cagcaacctg 235140 aagagcacgg cgcacggagg aaagtagact ctagatcttt aagatctgat ttcatacaaa 235200 atgagaggtc taaaactaga tgccatagga gagaaaaagt aatacgtttt cctcacacat 235260 cttaaggttc gtgactgagg tacctataat gaaagacaga ttaacaggag aaaaacacat 235320 acatactttt tttttttatt tatttatttt taagacagtc tcagcctgtc acccaggctg 235380 aagtgcagtg gtgtagtctc agctcactgc aacctccgcc tcccgggttc aagcaattct 235440 cctgcctcag cctcgcgagt agctggtact acaggcgcgt gccaccacgc ctggctaatt 235500 tttatatttt tagtagagat ggggtttcgc catgttggcc aggctggtct tgaactcctg 235560 acctcaggtg atctgcctgc ctcaggctcc caaagtgccg gcatcacagg cgtgagccac 235620 tgcgcccggc cacacacatt actttaagct ttacgtgaca acgtgggaac cttcctaaat 235680 aagacccaaa gaaacaggaa cacctatgta ttttttttct ttcttttctt ttcttttctt 235740 ttcctttttt tttttttttt tttctgagac agggtctcac tttgtcaccg agggtggagt 235800 gcattggctt gatctcagct cactgcaacc tccacctccc aggttcaaga gattctcctg 235860 cctcagcctc ctgagtagct gggattacag gtgcacacca ccacacccag ggctaatttt 235920 tatattttca atagagacag ggtttcacca tgttgaccag gctggtctcc aattcctgac 235980 ctcaggtgat ctgcccacct tggcctccct aagtgctggg attacaggcg tgagccaccg 236040 tgcccagctg gaacacctat gtatttttat gcttagattt gatgcaagtc gacagtcgtg 236100 tagaagtgtg attggatgag ggggcatgat ctagcagtaa taaaccgagg ggaatttggc 236160 aaggcctgtt tgttcaggtt cttcttggca tctctgtgtc ttcaaggata aggatgttcc 236220 tttcctttag ggatagagag ggcacctctg gaatgaaagt ttttgactgc tttggggaga 236280 agggtggggg aaaggtgaga gaaagacctt cctgcttctg ctgttttctc aaatgtacat 236340 tttgggtagt gtgtcctgaa ccccatcaat gaacaggctg cctctcgttg tctgtgagtt 236400 gatttgcccc ctctaggact ctctcctggt gccaaaagac tagcttcctg ttctttcctt 236460 ttggtcaggc actagggaca caagagctat aaataagcta ccttcccagt cctcaatgtg 236520 gtcagagtgc tggtgtaagg acatctggtt actgaaaaca gggccaacct aatatgaact 236580 cagaaccaac cccaagtggg tgtgcacagg aaatgggagt ttaaatctgt acagcccttt 236640 tttttaaaaa aaaaagcaat tttagtttac atgttaaaat agggatatat tagccagacc 236700 atgtggtgtc agcctgtggt cccagctact ctggaggctg tagcaggagg atccctcgag 236760 cccaggagtt tgaggcagca gcaagctgtc atggtgctta taaatagccg ctaccctcca 236820 gtctgggcaa catagcaaaa ccctatccct ttgcgggggg aaaaaaaggc attttttttt 236880 aacctaacat ttattaacca cttacgttat atgatttcaa tactcaccaa cccttgagtc 236940 aagcactatt cttatcccca tctttcacat gaggaaactg aggcacagtg aggttaagag 237000 actgtccctg tctcgtacac aggcagccat cagcacagtg aggacttgaa gcaggatggc 237060 ttgcaggagg ctgtgagagt tggagcctca tggtcattcc tttggagcct cagtgagcag 237120 gtaatttggc ctggcatttc cacttccagg atttgtccta agggatcagt cagacaaaag 237180 gactctaaga tgaatgttct gggatatttg ttgcagctag gtttatcatc tttcgggaat 237240 cagggcaact gtcacatccc caaagaagct gtcttgccac cttgtctcag tcgctacacc 237300 cccatcactc ctatcccatt agttaattct gctatcttca tagtttcaca gtctacaatt 237360 gtttattggc ttacttgttt cttagctgtt ttcctgactg gaatataagt tccatgtagg 237420 cagggagctg ttctctccat tacctaaaat ggtagctgac acataaagca tattcagtaa 237480 atatttcttg aatgaaatga acatattaat ggcaaacagc tggggaaaaa ttaatctttt 237540 tttttttttt taagacagag ccttgctctg tcacccaggc tggagtgcag tggtatgatc 237600 ttggctcact gcaacctctg cctcctggat tcaagcgatt ctcctgcctc agcctcccac 237660 gtagctgaga ttacaggcgt gcgccaccac ttctggctaa tttttgtata tttagtagag 237720 atggggtttc gccctcttgg ccaggctggt ctcgaactcc tgacctcagg tgatctgccc 237780 acctcggcct cccaaagtgc tgagattaca ggtgtgagcc accatgcctg gccaaaaaat 237840 taaatcttac tccataggga attggcctat ccatgcaata gaatacttgg aagtcattac 237900 aaatgattgt gcggatcatg tcgagcataa acagataccc tgcctgtggc tgagtaaaaa 237960 aggccggtga cagaatgcat gtgcagtgtg gttgccgtac tggccggggc tgctggcagc 238020 taaccacaga atttcgttta ctgagtgtaa gcagaaaaca aaacagttta ttacaggcta 238080 tcgggtaact caccgaccct cgagggtgta aggaagggtt ctgcagacaa atgcaagatt 238140 gggagcccaa gatgggagtt ctgcctcacc tcaagtgctg cctagttgtc tggattccag 238200 agaagtctcc taacctctct gttcttcagg cagatgtgga taataaaatc tgtgctgtcc 238260 acactgcagg actgttgtga gggcaaatga gatcacaggc atgaaagccc tttgaaaagt 238320 tagaagagga ctgtgtatat attgacatca tcgttatcag gtgattttga acgttggaac 238380 acatgtattt tgtccccaag cccctggtgt tggcacacca ttgggacacc attggtcctc 238440 tctgttagct gcctgcacat cactcagtgt taagatcccc ctggcagtgg tctggataaa 238500 aaggccggtg attctggcag tcgtgtttgc taagcttgtc ctcaaatcat cttcggtgtc 238560 ctcttgtgac ttcagtcact ctccctgtgg ggtgacctgt gtctcagctt cgggcctgcc 238620 cttctcttga ggcacactaa tcttgccatc ttcgaaaaca ggctgttctc atctcgggtc 238680 tacactgtgg cagccacaaa gctcggcttt ttccctgaaa gtcttcccca tagcctgaga 238740 gctgacacct agcgcgtggg cattcaaagt cactgtcaac cagggcttca tgcatggttc 238800 aagccattga ctaggtatca aagaccggat tcaatgaggt tttaaatttc cgtacaattc 238860 cattttttcc atcctctttt tatgtttttt aaaaatcctt cattgcctac ctaccatcag 238920 aggaaaacag cgttgtgata tgatggggga ttttaaccag gtactaatat tgtgaaagag 238980 aacgttagtg gtcctgaaac taggcatatg ttgtaaggtg gggtgatttt cccacttcct 239040 gtatgtccag aggcccttcc tggcagaact tccagcccag gagactttca tcttcatctc 239100 gcatgaagga tacaatttcg ttttgacgca cggtttagag aagccgttga acgtccacac 239160 aatctgttat gctaaatcac acctggtgtc tgcacagaga aggctctggc aagagttttt 239220 gccactggga ccaaggcctc tgactcagaa gccaaaacat ggcagtgttg cagggcgcct 239280 ggctcaacgg cacgggaaat taacctgctt gttctcacgt taaatgcttt atgaaaattc 239340 accgggcgca aaaagaggga agaaaaccca agtggttgtg cagtgcgcct gcctggcacc 239400 agtgaaggaa tgaagctgcg gaaaaagtca atgtgaagag ctggcaggag gagaaggtgg 239460 aaagcgcgat ggaaatcaaa tgcggtgcca gccacggcat tgttttatta gcatttgctc 239520 gaggaaaaca tttaattata gaagatcgga agctcccagt gtttgtgagc taggtgacat 239580 gacgcaggct ctgccacttg ctccacgata cacatcttca gaggaactgt ggcacaccgc 239640 gacaggctgc gaagagaagc cacctcccgg gggcctggtc cttgctgggg ggcccttagc 239700 tgtaacagcc tctgttctcc agcgatcctc agtctgcctt ttttaaaaaa ttaagtgtcc 239760 tgctggccgt ccttcttctc cttcgttttc tggtttttcc acattatatt tttcttttcc 239820 ttgttgattt ttgaagaaaa taaaattgac aaagaatagg atggaaaagt actaccctta 239880 aaaatgctta tatatttgcc acctaaaaaa aaaacaaagc catttttcag ttatagtttt 239940 ctttgggaaa taattaggaa gcaaaacaac caagaataaa aaaaaataaa tgggggagca 240000 tgaggctgta gtgaactctg tttgtgcctg tgaatagcca ctgcactcca gcctgggcca 240060 gcagagcaag accctgtctc tacaaaatac ataagtaaaa taaatgatct aaaggactca 240120 gtatatattt aagcaacaga aatgaaaaca tgcaaaggtg gaaccaacat tacgaatgtt 240180 gatggatatt accaatatta ccaaatattg tgtggagatt tttttttttt tttttttttt 240240 tgagacgggg tcttactctg tcacccaggc tggagtgcag tgtcatgatc tcagctcact 240300 gcaagctccg cctgtgtgga gatatttttt attccttttt gttttaaagc cctgtctact 240360 ttaaaaatag tttgtgaaaa taatgatgca gtatcacgta cctgcaggaa gtatttcttt 240420 gtgttccatt cctgccatca catagctgat tgtattacct gatttcttca ttcgtgtctg 240480 ccaggaagac taattaatgt gctgctgaat ataaagaatc cttgtttggg atgctgccct 240540 gccacacaag gcagtgcttc ctccagaaga caagaagtca aggactggct tctgccgctg 240600 gctgaaatta gcattggctc agtttgttta gttgcaaggc tatgtgtgtc ttgtcattag 240660 acatttatac ttctgtggat aaactttata atctacttat ggagacaaga ttctttatgt 240720 cagcacctta gagaagtgtt gtagaagcag ttggcatgca gacaggagtc tcctacagca 240780 acgtgggcac agctgagtcg gtcttaaccc accttagggc atcctcatac ctgcccaact 240840 catacctgca gaaattgatg atgggcaggg aaataagtgt tttcctccac agaaatgaaa 240900 aaaagtttgc ttttttttaa caaattggtt tttgatatct gtgtgaaggg gacaatttgg 240960 atcggcttcc agtaatgtgt atcaggtcag ctggagaact agagggagtc actggctgaa 241020 agatgttgtg aacatcactc taaactgctc aggccaggga caggtgacac gtctgttatc 241080 tgatgtgtat ctggaaccat ggtaaggctg ccccattaaa ttatgagcca atcactcttg 241140 atttaccgtt aaaaagagtg aaaggctggc ggaccctgcc ctgcacaggt aattcatggc 241200 acctttggaa aaaggcacgt tttcatcctc ataatgaaga aagctaggta cgaggtcctt 241260 tgatgacact gttccctttt gcttgtttac ttttattctc ccacgcagac tgagacccag 241320 caggaggctt ttaaaccaaa acagttaatt acctcctcta acccggagaa gtggggaaac 241380 ataaatatag cgagttaaga gggagagagc agctttgctc ctgactgtac tttgtaccag 241440 tcggttgggg aaggcagcta ccttctcttt cctcactgag cccgggctaa gcgagaccaa 241500 ttagaaggca cgtgccaggg agtgggtcca catgctacca tactgttggg cttccagaat 241560 tctttcagtg ctctggagag gagcccacct gagaaaccca cgtacagata cccattccaa 241620 agacaacatt gagtagcttt ggggctctgg accctccttc gaaggaagga actcttgggc 241680 aggtggagtg agcagggacc cccaacttga ggatggatcc tcccgaaggc aggcagggct 241740 gcagggcagc ttctcagaga tacttctcaa ctgagctgtg agtcatgacc tgtcaccacc 241800 atggtccttt ctccccaatg gaacggagcg tcattccttg tgtctccaag ccctgggctg 241860 cccctgccct tcagggctct ccattgtctg cctgtctgtc tgtctgcctg tctgtctgtc 241920 tcctggttca agctccctcc ctccatagcc tcatatgtac aaatcatcac cttgctgtgt 241980 tccctcactg ttcctgccgc tgccctgctg ctgtcctttg cccatttctg gctctctcac 242040 ctcctctgca cttactgaaa tcctgttcag tcttcagagg ccacccgagt cccagactcc 242100 cctcctccaa cccccttctc agcttgaggt gccgtcccct gcttctaagt cccaagggcc 242160 ccaggatctg ttccactgac tccaactgtt acttcacttc tcattatatg gggctttcat 242220 cgccacaact ggatgataaa ttcccagact tcaacaggga gtgatttatg gatcttttcc 242280 ctatgtccca cacctgtccc cagcacctgg tgcagtggat tgcatttaat taatccctct 242340 ggataaaaag ttttaaatgt accagaccag catcatcagg cagaatctgg gcatggtatt 242400 caggaagttt tctcttggga atcacaaaca ttctttaaaa aagggcacat cccctgttac 242460 ctaaatgcct tcaagtatct ggatgtttgg ccataagtac ataaaacaac cagatgagtg 242520 attgtgtttt tcagttttcc tctggatcct tctgccacct attccctggg acccctcgga 242580 gacagtgggc accactcccc attcctctgc ccacagattg tcccggctcc ctgtgcccct 242640 tgctgccctg ctagaaacca gaaattctaa ctttgcccct ctgaggctgt gaaaacacag 242700 agtaaaagtg ggaagagcca tgagctagca gattccacaa ccacagacaa atctgagcat 242760 ggcggtggtt aatagtattg ggaaagatgg ctgagtaccg tggctcacgc cgaaaatccc 242820 agcactttgg gagaccgagg caggcagatc acctgaggct tggagtttga gaccagcctg 242880 gccaacgtgg tgaaacccca tgtctactaa aaatacaaaa attagctggg cgtggtggca 242940 gtcacatgta atcccagcta cttgggaggc tgaggctgga gaatcgcttg aacccaggag 243000 gtggaggctg cagtgagccg agatcgtgcc attacactcc agcctaagag acacgtgaga 243060 ctccatctca aaaaaagaaa aaagaaaaaa aaaacactat tgagaaagac agtgtaagct 243120 tgtggtacgt aaatactctg tcttttttaa aagttgtgtg tagccgagtg tggtggtgca 243180 tgtctgtagt cccagttagt cgggaggccg tggtgggagg attgcttgag cccaggagtt 243240 taagaccagc ctgggcaaca tagtgagaca ctgtatctac aaaaaataca aataattatc 243300 tgggtatggt ggtgcatgcc tgtagtcaca gctactcagg aggccaaggc gagcggattg 243360 ctggggccta ggagttcgag gcagcagtga gccatgatcc tgccactgca ctccagcctg 243420 gctgacacag caagaccctg tctcttaaaa aaagtctgtg caaagtgtac gtcaaagcca 243480 cactactgaa tcataaaaca tcggcagtgc ccgcccacca agggcatctt ctcagcacca 243540 gctccacatt gtcctatgag tttgagtcag aggtgcctca gaggcccata aggatgcctg 243600 tcaaggtctt cgcagaaata ccaaaggcct ggcacatata gttaaggaaa atccaccagg 243660 aggagatgga aaaagggcaa ggtaaagagg aggaagagag gggaaggtga cggatagggc 243720 tatggcagca gagagccagc accagccagt tgccagtcag ggccagggca aggcagccaa 243780 ggaggcagac agaagtaagc cccttctttc cactggagtt ttctctttcc tgggaatttc 243840 attgtatttt gttgaaaaat aaggtgtgaa aatacaaaac aaaaatatca cgatcccccc 243900 aatccacacc atatacaaat atatatactc aaaatgtatt aaagacctaa atgttatagc 243960 taaaactatt aaactcctag agaaagacat aggtatatat ctcatgacct tcgattaggc 244020 agtcagtggt ctcaagatga tagcaaaagt gcaatcaaca gaagaaaaat agataattgg 244080 actttagtaa aattgtaact tctgtgcttc ataggacacc atcaagaaaa tgaaaagata 244140 gcttcagaat ggaagaaaat attttcaagt catctatctg gtaaggattt gatatccaga 244200 atatctaaag aactgttatt ttgttgttgt tataactcaa caacaaaaag acaaacaggc 244260 ctgtttaaaa gtgggcaagg gacttgaata gacattatcc aaagaagata aacagatggc 244320 caataagcac acacagagat gctcagcatc attagccatt ggagaaatgc aaaacaaaac 244380 ccattgagca tgcacatcac accactagga tggctgtgac caaaaacaaa ccctgtatca 244440 ataaaataga aaatagcaag tgttggtgag gatgtggaga aatatgaatc ctggtgcatt 244500 gccgatggga aggcaaaatg gtacagccgc tgtggaaaac agtttggcag ttcctcaaaa 244560 agctaaacgc agaattacta tatgatccag caattctact cctaggtata tacccaaaag 244620 aattgaaaag agggactcaa agagaaaccc atatgccaat gttcatagca gcattattca 244680 caataaccaa ttgtgaaaca atccaaatgt ctaccaacaa atgaatggat aaacaaaatg 244740 tggaatagac ataaaatgga atattattca gccataaaaa ggaatgaagt ttggatacat 244800 gctgtgacat gaatgaacct taaaacatta ttatgcttag cgaaataacc agaaccaaag 244860 aacaagtatt atttcactca taggaaatat atagaataga caaattcatg ggtacagaaa 244920 gtaaattaga ggttaccagg agctaggggc aggggaaaat agggagttga tgcttaatgg 244980 ttatggagtt tctgtttgag gtgattagaa gttttggaaa taggccaggt gtggtggctc 245040 atgcctataa tcccagcact ttgggaggct gagtgggtca cctgaggtca ggagtttgag 245100 accagcctgg ccaacatggc gaaaccctgc ctctactaaa aatacaaaat tagctgggtg 245160 tggtggtgga tgcctgtaat cccagctact cgggaggctg aggcaggaga atcacttgag 245220 tacgggaggc ggaggttgca gtgagccgag atcatgccat tgcactccag cctgggcaac 245280 aagagtgaaa gtccacctca aaaaaaaaaa aaaaaaaaaa aaggtttgga aatagtggtg 245340 atggttgaca atgttgcata agtaattggt gccacattgt acatttaaag aagatttaaa 245400 aggaaaactt tgttttatat atatattgcc cccatttttt aacgggctaa ggatgtaaat 245460 agacagttca ccaaagtaga tataaaaatg gccaataagc acatgaaagg attctcaaca 245520 tcattagtca tgagagaaac acaaatcaaa actacaatga gagaccactt ggtgataccc 245580 acgaggatga ctagaataag aaagacatgt ggtagtaagt ttcggcgagc atgtggagca 245640 gttggaaagg aaccctcaac acacagctgg caggagcaga aactggctta gccactttgg 245700 aaaacagcgg acagtttctt aaaaggtcag acatacagtt accatatgac ccaggaattc 245760 tactttctct taagtatatg cccaagagaa atgaaaacct atgtccatat aaaaacctgt 245820 attgaatgtc cacggcagca tttctcataa tagccacaaa gtggaaacca gccaggtgtc 245880 cattaactaa caatggacaa aatgtgacct atccatacaa tagaatataa tttggcaata 245940 aaaaagaata agtatggata ggtgctacaa catgaatgaa tcttgaaaca tactaagtga 246000 aagaaggcag tcagagaaga ctacctattg catggttcca tttatacatt ccagaataag 246060 caaatctata gaggcagaag gtagaatagt ggttgcctag gtctggaggg ttggggaaac 246120 gggagtgact tgctaagaag tatgaggttt cttttcgggg tgatacatac cttctttttt 246180 tgttgttttt gagacagtct tgctttgtca tccagcctag aatgcagtgg tgcaatcaca 246240 gcttactgta gcctcaaact cctgggctca agtgatcctc ccactgcagc ctcccaagca 246300 gctgagacta cagctgtgtg ccaccacgcc tggcttatgt tctaaaattg attgtggtaa 246360 tggctgtaca actctatgaa tacactaaca gccactgaat tgtacactta ggtaaactgt 246420 atgtcatgtg aactttatct cattaaagct gttatcaaaa tcacaaacct aaaaataatt 246480 ttcaccaaaa tgatttccca caaataacaa ctaaagcgat gtttcagtca ttaactagaa 246540 tagtttttaa ctttttattg tggaaatatt caaatatata caaatgtaaa gagagtagta 246600 taaagaactc ccatatactc atcaatcagc tccaaaaatt gtcagtgttt tagggtgctt 246660 tcccccctac actttattaa aaaaatttca agcatcagaa aagttggaag attgtacagt 246720 agaaaccaat atactataca cacctcctat attctcccat taatgtttac tctgcctgac 246780 ttaatctgta tctgaccatc cattcgtccc tctctccatc catcgatttg ctttgtatta 246840 atatatccat ttcaaagtaa attgcagaca gcagtacact tccccttagg tactcctgca 246900 tgcatatgaa tgactagagt tcaatatttg tttacagttc tctttgtgtt tttgaggtga 246960 aatttatata caatgaaatg cacaaattta aagtatatgt tctatgaatt ctgacaaatg 247020 tataggtttg catgactcaa agccattgtt ctaacatctt taaaaaatat ttttaattgg 247080 ttggagacct tcaaaacaaa ttcttttcat aggtttattg tgttttagtg ttggagtttt 247140 ttggtaaggt tttctctttt tcaattatat ctctgaaggg cagaaatacc aattatatat 247200 tataagctac ccatctatac acatcctcag ccttcttagt cttttgaatg aaagccaatt 247260 tagcatttca ctataaacct gtgttttaat gtatgtttca tgattaacat atcaaaaact 247320 ttgctctgcc aaaatctaca ttttcagagt aaacagggtg cctggcatgt aacgctttgt 247380 aagatgaatc agcacataca attttaagcc agttaaccta cagtatgctc aatattgtta 247440 taggttttct ttttttcaaa aacaggcaaa ctaagttttc tttttcatgt ggaaaaaata 247500 acaggataga aaactcaaca ctcaccttgc ctgttgaaac atactaccag gttgtaataa 247560 tctgagaatt catttgcctt tttttttcag tgcagtcact acaacagtct ctgatcatta 247620 ttacagtaaa tttttacaca tttatgagaa aaatccaata taattgactg gtgaggatgg 247680 tctatgtcct aagcaatgct gtttttaaat acaaattgat aaaaagttat atgaaaaagg 247740 ccgtccttaa atagaataaa ttcgttccgt tttttatttt aaaccaaact tgatcttgac 247800 attttcaata agattttcat agagatgctc ctggggcctt ctgctaaaaa tttggaccac 247860 ttcatgcccg tgacatgaca tcattttaca cattagatga aatgaaaatc agatgagatg 247920 gacacattca gaagggatag aatttactgt cgtttttgaa tacgtggcat ggcaattgcc 247980 ttttgcagga tgaaaatatt cattgtactt ttctttcatc acaaatgttg tggatctccc 248040 tggagtctag aaagtctttc ctatttctta attaccaaat cttgggtcgc acatagcttt 248100 ctcgttgttc ctgttgcacc cagggctgtc tctgccattt cctctgaaaa caactataca 248160 ttaacattca aggtttgagt cgggggctgg gaggcgaagg gaaaggtgat aattcagatg 248220 ttatgaaact gtgataatgc tattatttaa ggcacttact tgggtatgtt tatactttgt 248280 agttttataa ataagcccaa ggggctcctc ttggttgtca caatccccct tgaatctcgt 248340 atcctgtctg tctcatccta tccgacagta gaattgatgc cgctctaatc cctggaagtt 248400 tggaactaat gaactgactg ctgagctgcc gccacggagc ttggtcccaa actatactgt 248460 acttcacact cgatttattc tccagatggc gagactgtgc cgccctgccg cgagggacca 248520 cctcttccac tggagtgtaa aagtggacgg atgttgtttt ctttgcagat ttgatcattc 248580 tgagctagaa acttgcgagg atgattagtt attagcttta atgggtgcca attgaaccaa 248640 ctgcacgcat attttctcct ttaatttcag agtctgcagg ttttggtgat ggttgatttc 248700 tccgctttct tacgtcacca gagcgtgtct cttccccagg tgataggaat ccagtctctg 248760 aaatcatagc acgccttggt tcctggccca gacagagtca cctaatacgg tggcttatgg 248820 ataaggacaa gtttattagc cactggtcca ctgcactgag cagcatggca cgaaatatcg 248880 attgaatgcg gcaactttgg gaacaccatt ttttagaatg ggggcctgca aagattgtaa 248940 tctgtgccaa cttcctctat gacctgggca gagtccacct ctggatcaaa catgatccag 249000 aacacgctat ggtaattagt ctcttcgaag ttctaatgta actgttgata aaggccttaa 249060 ttccattatt cagtcatttc cagcttgtca gatcttgggg gacaagttca ttccacagtg 249120 agaatggctc accaaggctg tcctgtagtg ttaacacatt tagaatgcag tccctctcaa 249180 acctcatttt aaacaacctg tattactcct aggatataaa agcccccata aaagctcttt 249240 ttggggtgac cgcttttacc ttaatttcct ttttctcctt cctccaggaa gcacttacct 249300 cccaatagtc gtagcaggtc accctgagag cccttctgag agctggggtc agccaggcag 249360 cctcttgcta atccacctaa gatggatatt ggagggatgg tcagagccaa ccaggagcca 249420 aagaaagaga gaaagaaaaa gaaggaaagt gtgaagcgtg aaggatgagg tggtggagat 249480 gagagagctg agagcgctgt tagcaagaag tacagtgtgt gtggcagaga gagggaaaaa 249540 gagaataaaa tgaacagaat ttctttcttt tcacaactgg gtggactgtg actctctcga 249600 actgaacacc cagaactaaa cttaattgtt cttagaaact gccttcctcc caacccaaca 249660 gatggcatgg gcgtgtttgc tagcacagtc aaatacttca ccctgaaaat accaaaaaga 249720 aaaaaaaaaa ttcaacatgc tcgctggttg gggtaaattc actgaagttg ttgagtgttt 249780 tgggatatat accagaggga tgcacacttg gtttatgtaa attgtaacaa gcaacagccg 249840 gttaataagg gtgtcgtatg gcaacttacc tcaaaagcca tcctctgttt ttggaaatgt 249900 acagaatgat gaagtgtaaa gagcttggtt tccattctga gccaaaattt tttaaatgct 249960 gagtattcac tgctcattat tataatatga aaagtactaa tcagattatg cctaaaattg 250020 gaagtaggta cttcatttgc agccaatttc acaagggccg aattttgcta agtaaactgg 250080 aatgtgctga aaccatggca atccgacttt agataaaaat caaacaggtt tagaacatga 250140 gctttgaaca aacaagtccc ttcaaatcca agtgaaacca aacagcttca agatcagatt 250200 ttgtttgaca ccagccaaca ttaacaattt aggaagttga tgttgccagg gatcctgcgt 250260 tcttgagcac acatgcagat tagaggatgg agatgatgac tcaaataatt taagctttaa 250320 aatgcagtat ggcctaaaaa actgagtgag ttcccttcaa ttttccattc atactgtccc 250380 agtagactct ttgcaaggct gacttagcta ttaaaaggga acctggaagt cacattgaca 250440 aactccagca atcttatctc gtttttttgt agctgcatag gctacacaga gaagaacatg 250500 ctttaggttc tccacagcca tggatctaaa tgtgccttcc aaaaagctga aagtatttca 250560 gttttttggt ttgtttgttt tcgcttttga gatggagtct cgctctgtgt cctatgctgg 250620 agtgcagagg tacagtctcg gctcactgca acctctacct cctgggttca aacgattctc 250680 ctgcctcagc ctcccgagta gctggaacta caggtatgtg ccactacacc cggctaattt 250740 ttgcattttt agtagagatg gggtttcacc atgttggcca ggctggtctt gaactcttga 250800 cctcaggtga tccaccccct cagcctctca aagggctggg attacaggtg tgaggcacca 250860 tgcccagcca gagctcaagt atttctccca gcagctctag acagctttag agccaagata 250920 ctgagccaac ttctgctctt cacctttaag attttcgtat ttagggccgg gcaccgtggc 250980 tcacacctgt aatcccagca ctttgggagg ctgaggcggg tggatcacct gagatcagga 251040 gttcaaggtc agcctggcca acacagtgaa accctgtctc tactaaaaat acaaaaatta 251100 gctgggtgtg gtggcgggtg cctgtagtcc tagctactca gggggctgag gcaggagaat 251160 cacttgaact caggaggcag agattgcagt gagccgagat tgcgccactg cactccagcc 251220 tgggtgacag agtgagactg tgtctcaaaa aaaagagaag attttcgtat ttaatggctg 251280 taataaagaa tgcatggtag agcaagtggg cgagttttat atctatggaa taaaacaaag 251340 gtatgatgtg gaaccaagcc attgctggct gcatcatctc tgactttagc tagtctgagc 251400 tctctcttgc ttttgtctaa gttggcctaa ttattggcag atgaagctct gtaaatcagg 251460 acttcacaga gcagtcctaa actgtcttag gtactcttcc catctgaccc gacaactcta 251520 agctaccgtt tcctcacatt gtttaactca gaccacattt ggaagcattc cttgcttctc 251580 cccgctcata gacccacatc tgtctggttt aaatctgctg tcctgggttg tcttgttgct 251640 gggacttaga ctcaatattt ggcttaaata attctttttt gtctctgctt tggtttgcta 251700 ttttcctaga tcagtattgc ttttcaaatg gttatatatt attgagacct tttttgtaaa 251760 ctacattcat cagcagtgag aagctttaaa gttttattag tatcataaaa acccttccca 251820 aatgaaacta cttttgataa gtgttcattc tgacaatgag aatttgttga gggctgttgg 251880 caagttggag gagttggctt ttgaaactga aattggcagg aagtaatgac ccccagtgct 251940 ttctttctct tgactccagc ctcacccttt ccatgcactt ctttctctcc ccaaccccac 252000 cttcattgcc cccaagccaa agccaagaaa taacatactt ggtttcatat agtttttctg 252060 gggacaattc aaatactgaa gcagactttc agcctttcag cttttctgaa ctgtggagca 252120 aagcctgtca agtcaaagaa aaaaaaagta tttgtcaagc acttcatgaa gggattcctt 252180 gccttccacc tgaagaagtg ggagcttttc ttgtagtaca cattgtcaga ttcctgtgag 252240 catcttctta attgaatgtc aagattcaac tcagttgcaa aaaaatagtg agtaaaaaaa 252300 gcatgatgcc tgtggaaaaa gaaaaatcct tattttttcc ctaatgtgaa gaagctgaca 252360 gacgagatgg ccacaatcta gatgttagcc aatttcttat gtttattaaa tgagaaagtg 252420 cagggaaaga acatagaacc atgcttagca cttaatgctc aatcagtgaa aacttaccca 252480 ttaactattt tccccttccc attgggaagt aatgctaatg agaaagacga cacttccata 252540 cagaagcaca cccatgtgca ctgcggtgcg tctcggctat gttatagcta tcgcgaatga 252600 aacctaaaaa tcaactgctc acctttcaga ctggatgact cctttcaaat attatttatt 252660 tggtggacag gaaatgtgta gatagaataa tggtgctcag actctgaatc cacataacag 252720 tttcatcaac catttgatgg tgctcccctc aatgataaaa ataaacaata aactttttat 252780 tgacacttac agaatgaagc tcgactgaga attgtaaaaa ctcttgaaga cattgatctg 252840 ggccctactg aaaaatgtgt gagagtcaac tcagtttcca gtggtctggc ggaagaagac 252900 ctagagaccc ttttgcaatc ccgggtcctt ccttccagcc tgatgctacc aaaggtggaa 252960 agtcctgaag aaatccagtg ggtgagtagc taatgctttg ccttaagact caggagcagc 253020 taaggaggag tagcaggaag aagggatctg ggtgccacag gtttggaaaa tgcatgcaga 253080 gagcagagag gaagggaatt gagaaaaagc agtaagctca agtatccgtt tcttttacac 253140 aaggaaaact cgcctttgcc caaagtgttc tatgaaacaa ctgcactttt gaaatgatgc 253200 ttcgcttcct aattggatgt gtggtttggc cagaacagcc tcctcagtag ccctcccaga 253260 gtaatccctg gaaactaggt tgcccgagaa tctcatccct tcctccaccc tgcccggccc 253320 taagccaagg cctccacctg gaagagcagt gacgtaaatg gcccttactg agattcatct 253380 gaaatcatcc caggcaggga gggcacattt gccgcatatg aaaaaatgaa cccaaagaag 253440 gggaggaaaa ggtcactctt tagggcaact ggaggaatga acaggaagct tttaactagt 253500 ggtttcaatt agcactgata ttatttcctg aacagttctc tagtgcatcc tttttaaatt 253560 gctgacaggt gtgtttgtgt ttcatgacag acttttcagc caataaaaac ctgaaatgta 253620 aagtggttgg catgtcaaat tacttaagaa aacttttgaa ataggcctaa ttacactatg 253680 attgttttaa ttgacaaagg gtggaggggc tagattttat ttgagggtcg ctattattct 253740 gcagatctct actgaataaa ataacatttc actgtgttgt tctgggacag aaaatgtgtc 253800 attctgggcc ctgtgaggtg tgaaaactgg aagcgtttgt ggtcggggcg agtgggcagt 253860 ggtggtttca tggaagccac atctagtatt atctctgagg ctgtggctgc caccacagca 253920 ataccctgag ttgttgtaac acctacgaaa ctgctcacct gctgaatgca cccgatgtgt 253980 gaggtctgcg ttgcccagtg ccacggccac tatgacatgt ggcttctgag cattgaaacg 254040 tggccagcac aaatggagat gtgctggaag tgcaaaatac acactcgatt ttgaagactc 254100 gggactcact gaggggacaa aaagagaatg taaactatct cgataatttt tatattgatt 254160 acacattgaa ataatatttg ggatctattg ggctaaatac aagatactat taaaattaaa 254220 ttcacctgtt tcagtttacc ctcaatgtag ctacgagata atttaaaatt attatatgta 254280 gctgctgcta tacagtttct tttggacagc tctgtgttgg atccttcttg aagacccgta 254340 ttcaaggacc agttatttat tgactaagct ggagttcttc tctccagggt taccctcaga 254400 agctgggaga tactagttaa gagtatgtta atatcctgga gggtcctgag cccattcaga 254460 tatgtcttaa gttgattgaa atggactctg aagtcactgt tcccttttgg tttcatagtt 254520 aatgcctatt tatcaccgtt attaccttta acttaagatg ggggaggggg agacccagcc 254580 agccttccgc tatggcttct gttcactgtt ttaaatcctt ggaagtgaga cacatacaga 254640 aatttaaata gaacttctag ttaacagaag tccttttggc tgtttatttt ttcctctccg 254700 tttgtattta tgcgaagcat aaaacccaga gcctgatgca caactgaaag atgggcttac 254760 ttgttttctt ttgtgtgaga atctcttgct cgccttttgt cgctagtgtg ggttcttgtt 254820 tgactggcac ggcttattgg actataacaa gcgtaaccct gcctcctttg tcatgggaca 254880 attctcccac aaatcccgaa cagtgtgcat tcttccaaca cactattggg tgtgcactgg 254940 aattgaaaga atcgctgagc cctgctactt catctcctcc ccaatctctt tgtgatttct 255000 cccccttctt ctcctccccc taccccagtc ccctccacct cgctgaaatg aacactttac 255060 caggccggaa acatttaatc gtctcctttt gaaaaaatta attgaaactt ctccactagt 255120 taccttttgt gttagtactt agtgcaattt tttaagaaag agggggagga ggaggaggag 255180 gaggatgggc tagaatattt aatttttaaa tgcccctatt ggcttaaaaa caaaaggcat 255240 tggggtgttc tcactaagaa cagggaatat attgtaaagt gttgacttgg ttttaaagtc 255300 catgattttt gtagttataa ctgtcatcac aaagaatggg gcaagtcact tcacaagttt 255360 tcttttttaa tgagaaaaaa tatccctact acatttttaa caccaaaacc actaatactg 255420 tgctaccact ttctagcata aatgagaaat aaattatatt ttattttcat ctacatcaaa 255480 tactatacat tttatcccct taaattgtca ccccctgctc cttcttgcta ttttggttga 255540 gttattcctt cccttgaaaa gttactaagg aggtgatgat gatgcccttt gaaggggggg 255600 cagtgggagc aactgggaat aattcttcat tactgaaagc tgtgatttat tttagcctaa 255660 ttgtaaagtt actgcaaatt gctcaaaagc tttttaaaga tcccagtgat tagatttttt 255720 aggggggtgg tgcaccggca aggagggggc agctagaagg ggaaataaca cctctaatcc 255780 cgcttctggt aaataggctg ccagcttttc aaatgagttt cctttctatt agtcagaata 255840 ttatgctaag ccttaagcat tagttttttt atgttgccat agcagcctta ttcctgcagg 255900 gtggtgacct gtgatgatta cagtacaaag cttatagggt cttgaaaccc cctttgaaga 255960 tgaaaagtct ttgatggttt atatttatgc aaatctctta gatatgattt acccaactga 256020 gactgaatgg agagatgatt aaaattccct tttcctttga tatctattaa tggctgaata 256080 ttccttaaat ttaaaatgga tatatatgtt ttcatcttta tttacaaaaa tacctttatc 256140 atacctgtgt ttcttctcta tctatctccc cacatcttat tagatctaga tagacataat 256200 agatttacaa tttagagtgt gtttttttcc cccttttgaa gagggggagg aatctgggca 256260 agagcttttg tatgtttcca gatgatagat tttggaattt gggctacccc actggcagca 256320 cagagctagc tgtgaactgg tctcatggaa aaaattggcg agctttggtc ttcaaagaat 256380 taaacttcct ttttaaggtc ttcctaggta agctaaaaaa ttatgaagaa aaaccttctg 256440 aacaaagggt aatggtgcta taatgaataa tatggactcc acgtagaagg ctgctgaaca 256500 gttgcactga tgtcagtgct gggcacgaaa caaaaacaga atggcaggta gaggaagagt 256560 tcattgtttt aagggcctac catttgcatt taacgaagcg agggcaagag gtcttaagta 256620 aatgcgtttt cagggaaagc gtttatactc tctccttcca gttctaactc ctaggcctca 256680 agttgctcct ttgggagaaa aaaattgtaa tgcttaggat tttactattt agtttggtgg 256740 gaacttcatt acctttttct ttggactttc ttcttatttt tttaaaaaaa ttcttttgtg 256800 tggacgaaag aggcttggat attacttcct caggtcaaag acttaaatac tacttctggg 256860 tctacatttc cgtgattgta cattttttcc ccactaatca cctatgacac ttctgatttt 256920 agtttgcaga caaattttca ttccacttaa aaggccgaaa acttgaacaa ccaatgaatt 256980 taatcccttt tgtggaaact gcaatgggtt tgctcaattt taaggtaagg aagccataat 257040 acggttaata agttagcatt ttatttatca cctaaagaga acttttgctt tcaattttaa 257100 catcttctta aaatgtgttt ctagaaagat ttataagcaa aggaaatgtt gagcaccatt 257160 tgttatctgt aatagtccaa aaaccaggtt gccagcatct tagaaaacaa tgaaatcagt 257220 taggtagaag gaaaagcttc ccagtccaaa atatttaaat gaagcatttg tatattccta 257280 gtaacaattt taactaatca ctgtgtaatt atatgctttg aattattgca tttatagact 257340 aaatgtacat gaaaatttgt cacccttatg aattaacttt gaaatgttct tttctatcaa 257400 atgtcttttc agtgggaaat gttctgccct ctctgtagca acattatcag taatgtctag 257460 cagagaagat tattgtttgt aagttcatgc acacaaataa tttgcagtac agtttttcag 257520 tttgccacat tagaatatct tctaatatac atgcgggaat attggctgag ccaagtgttt 257580 tcagccgttg tgtggttgca ctaaactacc ggtcttaaca aattcagagc tagctcgttt 257640 tttctcgttt atcagggggc atttatatta ttttccaaaa tatgcctctc attccacctg 257700 acctgcgaac atcaatctag cacccccttt cagagttcct agattccctt cccccacccc 257760 agcccccaca gagggcagga gaaaagaaat cactaaaaac aacagaaaaa acatagtcga 257820 actgtactgg agagagaatg tgtgagcggc aactttgagg ccttgggatg tgcagaaggg 257880 gtcgagtgca aatgtttggg gacctgcttc aaaccttgtc ctgtgagcag cttgtttaca 257940 caactaacca tacattcttc cagccagccc cagaatcctg agaatataat caaaagcata 258000 tccctaagat gcaaccagat tcatccagtg atttaatttt aagcactgct tcgccatttt 258060 attccataat gtacttagaa gcacttacaa tgtctgaaat taatcaacag tgtccccacc 258120 ggttcctcgt ttctttccca cccacgtata ttattagcag gttatatctc cacctttcaa 258180 gattcacggt tatgtctacg acgaatggta tttgccttga ctttcatata taaatgtcga 258240 agttgcttta tgaacacatc ttggatgact tgttgcattt ttattttccc ctccggagtt 258300 gcaggttttt gtgctgtctt taatcctgag accatgtgct tgatcctaat gcaaataatt 258360 caattagttt gattttaaaa ttccttcctt ctcccctgtg gttttacgag agtctcttaa 258420 agcaaaaacg aattctggaa agatataaat aacttatagt gcaagcaaaa tgagttaact 258480 caaagtttct ccaaaaatga gatgaactac aatttgaaca ttataactat attcatataa 258540 tccattaaac aaagcaaata tatacaatat acttatcttg gatgatatta aatacctttt 258600 gaaaggggta aatttgggct gcgtttttag gactgctttc agccaaactg tgttaagagt 258660 caggtcgtcc tgttactgaa atgcaccgtg cctcttccct ctgacgcacg cgtttccgtg 258720 agacttagtt ctgttctgct cttttacagg cagtgtgtga agaaaccctg aaggtcgggc 258780 ctcaagtagg tctctttcta gatgcagtcg tttttggagg agaagacttt cgagccagca 258840 taggtgtcaa agacatctct ctctctcttt ttctgtgtgt gtgtgtgtat atgtgtgtat 258900 atattttttc tttgcccctc aaggatggac atttacataa caatgtatat ttgccaacca 258960 tgacaatggt ttttcatgac aatggaatgg acactacttc ctgataattt agggctcctc 259020 atagctgccc tgcttctaga gcactgcatt attacttctg ttcatttata aaagacacga 259080 gcaatagaaa gcctgttgca gccccaggca tgctcaggaa tatatggcat ctcctttgct 259140 cctaataaat atattatgtg aacagcctca ccgttgcttc agtattttgt tttcatatca 259200 gtctgtgggc tgtctagatt tctaacgcaa atttaaggca atttcacatt tgccttaatg 259260 aattgttttc tacagaatat gcggtaggta aatattattt taaatggatc ttaaatttct 259320 cttacaatat gtttcgaact cttagtatta aatgtgctga ttttcaccga ttctcaccat 259380 cccttgtgag ctgcacttga ggggtctgca tgtttgactg gagaccgtga agcatttaga 259440 aaagaggccg aggccacaga aaccagcccc agtgacctga agacaggcac tttccctagg 259500 cagggagtgg catgttccaa atgtaaacag ggacacttcc ctcccctcag ggtgaaaaaa 259560 ctgaatttat ttgaatacga gtctttccag gagacttgtg tatccaacgg ttcagcgggc 259620 tacagaaggc atatcgatgc tttccagccc tctcaaaaca agtgccctcc cgtctcccca 259680 agttctccat ccagacagac cctgaagctg aagcatttgg ctcagaactt cagtttggac 259740 agggcaatcg cagcacacac agttctgtgc ttgctgtgaa acacgaacca ttgccctgca 259800 tagctgctgg gccacccttt gtggtgctgt ctttggactg gcacttttca agcgatgata 259860 agaaggaaaa aaatatatca ggagtccctt gcgaccctga cccagcctcc cagaatgggg 259920 aaggggcctt ctcttaatgc aggtagaagt aattctattg aaagatgcct tgtcagttaa 259980 acagacacat tcgaggttta acttggcctc cacgcgtccc tgtcttcatt tgtatttcaa 260040 taattttatt ttgcggagga gcaatttcca gggaggttta gatatctgta caaactgagg 260100 ttttataata aatatctggg tgcggtttcc aaagttaaag cctccttttt ctgttaacat 260160 cccattttca ggtgcaacaa gtagtaaaga aaccctggat attctctacg cccggcaaaa 260220 gattgttgtc atagcgaaag cctttggtct ccaagccata gatctggtgt acattgactt 260280 tcgagatgga gctgggctgc ttagacagtc acgagaagga gccgccatgg gcttcactgg 260340 tatgattcct gtcttagaaa gcagtgtcta aattagcaag cattccagaa aaatagaaat 260400 ttgacccgaa aacaccccta atctcatcag atatctccca tacttactcc actatttgaa 260460 atatgagcaa gtcacacagg ggaagaactt gccagacaca ttgtcatggt tttccttggc 260520 cctgcaagtc aacaaatcac tcattttatt tcctctttat attagttgct tttttttttt 260580 tctctccatc ctcttaatca ttttgttgta gtcttggctg acctgtaggg agggatgagg 260640 ctgctcaaaa agtgtttttg agtgaaccgc cataagaatt ttggttgatg gacagaagaa 260700 aaatctccta gaatatccaa aatttaattc atttctgaaa aaaaatgttg gtgatattgt 260760 ctttggtttt tgttttgttt tttactcata actagttttt tgctcttctg ccactccaag 260820 cccctcctct ctctcccacc tcccagtaag tgtccgtgta cctggcgaca cctacgggca 260880 taggctggca ctaggatcag cgggtccctt gcagtccggt ctggggcaca ggcgggtatc 260940 tgttgattgg tgtgcctggt cactcaggtc cccatgagcc aggggagcaa cagaaaattg 261000 tgtttttaca acagagatct atttttcgaa aaaccacaat aggagtctac acacaaacat 261060 acacatggag ttgcacacac acaaactgac aaccatggga aaaacacagt gcactccttc 261120 actcttacct gttcttctgt tgttgaaagt tctaagaata ttaatatcag aaaggcaccc 261180 gaataattag gaaaagagac gagcatcctg atattcctgt tataactgtt tttgaaatat 261240 atctaggtag cggttaccga aagaaaggtt tcataaagca ggcttaaacg tgaaaaatat 261300 cttaatggat gatgatttag tccaaaataa aactgaatga cctaagaagc tattctagtg 261360 ttatattcaa attaaataaa gctctgagtt tgttcttgtg ttttttacac aaagagctaa 261420 aataaatatg acccccccca attttttaaa taagtgtgat ctcgtatagg gaaatactct 261480 tcaattatct gaactattaa taaacgaatt ctccctgcgt ttcatagcga ctgaggaaga 261540 aaggagtcct ctgccacatc catgcaattg tgcttgttcc tgcctctttc caacggctgg 261600 ttaggatgtg acccaaatgg aaaagttgga gaaaaactcc atgaaattta tctaatagac 261660 cctgatgttg ttggcctgca atgtatggca ctggctgcca ggtggccaga tgttgctctg 261720 aaatgggaac taattcgata aaaaagagaa agcactgcat cgacactggc ccctccacca 261780 tcacccagca gaatctgagt ttcctctgcc tcctctgggg taaatgtttg ccccagaact 261840 tctctgggag ctggagagtg tctccaagat acaggactga attaacttgg cccctaattc 261900 aatcgcagaa gacaggctat ttcaaatcag gtttaaattt ctagactgtg cccagctcag 261960 cacgagaagc ttatggacct ggcactattg tttctccacg acggggagta ttaaatcgct 262020 aaaaaaaaag gggggaagcg aggataatgg gaaggcacag agggcacagt gcccattata 262080 tattcaaggg aacgaggcca taactaggga gccacacttc gtaggcagtt tgcaattttt 262140 agaaagtctt tgttgcccca attatatttc tgcataccaa taagaggtaa tcaatctgat 262200 aataagatag attatttgta gtcatttttt aaataaatgt tttttaatga gtactttaga 262260 ccactcagga tgtttgtcct agttgtttgg catttgattg ccataccttg ggccttgcac 262320 aaggagaaga aaaagaagga aagaaaaaaa aggaaaggaa aagtggggag gagagaggga 262380 gggatggagg aaggaagaca tgtcttatct gaagcaggtg gttgaaaggt ttaaaatcca 262440 atgaaagtat tgtgttatcc ataacgctgg taaggaagac taagtctgtg ctataaggat 262500 tgcctttact tttaaaaatg atacatattt ttaatgagtt gtagttttta aaagttagct 262560 gtagtttctt ttctgcggtc gtttcccaga gtcacagtcc atgtcgattg attttaaatc 262620 aatgcattgg ctgtataaat ggccattaac tttaggaaat tttttataaa aaagaaacca 262680 aaactaaatc ttggaataaa gctttaacag ctgacttagt cattacagtt actccagtgc 262740 tacatgctga gaagaaagat tataaatatg aagcactata ggttttcttc ttttttgcag 262800 tctattgtag aagacaaaaa tgacaccatc atacagttac ctaaaagact tgacaggtat 262860 tgatttaaag cacgatatat caagcggtac tgtaaaaagg atttcatggt cataaatttt 262920 aatgtcttcc aattttgcac cctctcagta acttgtcaat aacaactctt ttgtataaaa 262980 tatttgcctg gttcccacat gccattaaag tctgctatac agttgttgga atatataaga 263040 tgtgacaaaa gagaacttca catatgaacg ttcacacatt tctaaaacct aacatgtatc 263100 ttaaaattag cctcattgcc caaatatagg tactggagga tggagagcta gcagtgattt 263160 cacagtattt taagtagttt atgttttgct cctcaaatta tagtgcatgt accaagaagt 263220 tcccatgaaa tctggctttt tacgcattgg tgtaaattat gtacataaat tatgaaattc 263280 agggctaaca attaggagga aatgactacc agaactgaca tcctttatta acaatatccc 263340 gacaactatt aaattactta aatataatct cgatacctac taccgaaaaa agccctcttg 263400 tcatccctca tgttattcgt tcccagaaat tattcctcag gtaatttaag gaatctttac 263460 ttatataagt gtttaacatt ttattagtat gctgacagaa aagaatgaaa tagcaatgtg 263520 aggatgtttt aattatgcca ttggaaagaa aagatattat tatatttatc cacttaaact 263580 cttttacatg aaacactaaa aatatgtttt tacaagcatc attccttttt tcattctaat 263640 agaataatga caataggaat tgacagcaag gatataaaac atcaaggata taatttctac 263700 tgtctaaatg ttaaaataac tatttcaaaa gcaaagcaaa ctgatatacc aacaaatata 263760 ttcagcagag taaatgatca ttaagtgtac attcattttt aaagagccaa ttatgttcat 263820 aactttatca cgtaacaata taatctcatc attattataa cattaaatta tgttgcattt 263880 tattaatgat ctgattggat tctacacttc cctgattgtt aaattgtttt tttaatgact 263940 gcattatttc acaaaatcct gtggctctta tctttgtgtg atgttttcat ttaaaatctt 264000 tcaactataa aaagaatcat aaatcttttt ggaaggtatt tctacagaga taagatttct 264060 tctgggatat gtagggtgct ataaagaggg aaatacccag tcttgattct ataagccaaa 264120 agggaaaatc tgggtatatt tttggacaga gaaactttaa gtatttattt tttaattttt 264180 aaatggagta atctaaggct gcagtgttca aatctgcctt ctattttacc atactgaata 264240 aaatattttc attcaaatcc aattttctat tgggggttag aattgacaca taaactgttc 264300 atttaaaaga aaaacaatta aatatactat tgtaaagctg tatttgatag taatatagtt 264360 gtaatgactg cctctgtaag ctttatgaaa accagcagac catttctaag agaaatcatg 264420 gaaagaggta taattctaca aagaaagcaa aagacacctt ataaaatttg agagaattct 264480 catttaattt ttttctactt caactcaaaa taatccctct aatttgcaga cattatcctt 264540 taaagtccca gccaaagcag ttattcaaca agctgcctag tcagcccacc tgtaactaaa 264600 aataagagat tatctgccct aaggtggcat ttctatagga tcggaaacac aattacttcc 264660 attgttgtag ttgtgcttct gtggtattct ggaaaagcct gtctgattgc aggttttgtt 264720 tgttttgttt tgtttactca ataaaaagtt ttaaattagt tatttaacat acagtctatg 264780 aggccttcag gaacctcacg cgatagaaac attttgtttg aacatctgtt cgttgtttcg 264840 tggttccgat gttattaata ttcttgtagg taagcaggtg attcacccta accaaattgc 264900 cgtggtccag gagcagtttt ctccttcccc tgaaaaaatt aagtgggctg aagaactgat 264960 tgctgccttt aaagaacatc aacaattagg aaaggtaaat gttttgttaa tgccttgggt 265020 gagagcagta ttgaaaatat tgtcgggaag aatgaaacaa atatgttgtg tgaatggttt 265080 aagaaaactc atcgtatctg gagagggggg aaagggaggg aacacaacat tcaccagtga 265140 gaaaattgct tgagatagat ttgccctgcc catgttccta aatacttcac taactggctc 265200 tcaagtccct cattttattc ttttcataaa atatattggc agccttagag aaaatagaag 265260 tctgtttagt ttttctctac agacttctat gcagcattca tatgaaaata atcctagatc 265320 aaagtgagaa caagttgtaa tgaaataaac acagtttgac taaatggttc ttgtggagga 265380 aagaaataaa ttgcaagtta ttttaatttg gggggaaaaa agtacagaaa tctcctccgg 265440 tttagtcatt taagagtggg aggttgtata tgtgtttgta ccaatttctg gacctgagat 265500 ttggatggaa tggaaagcaa attaacactg gagtacggtt gttcctaatt tagtgcatca 265560 ttgagcctcg cgtttcctgc tctgtgggtt tctgctatgt aaatattgca gtggtaatgc 265620 acaatctgtc tccactttgt gccagtaaca cttaaattag gtgtcgcctg aaggaagatt 265680 ttatgctagt tgcagcattg tcagttaatt atcttaaagg ttatttgcaa taataccgtt 265740 tgcctctttt taagaggata ggagggaaag ttacatttat aaatctatcc tagaggtaat 265800 ctctaaactc agcctgtgac ttccagaagg agtaaagttt tgatacctat aatgcaaaat 265860 tacttaggag aaagaatatt gaaaatttat tacagttctg aatattaaac attcccccct 265920 gcaaaaaaaa aaaaaaaaga aaaagaaaaa ctggttttta gtggtgaccc tgaacctgtg 265980 acatccatgt gagacatgtc cctcgcactt ttcactggca gcaaggacac ctgaaaatcc 266040 caggacttgc caaagtgggc aacaatatta aatgggtcat tccctaagga tgtccacatt 266100 caacccatgc acacatgggc acactcacac accagcaggc tcatctttgt acaaactcac 266160 acttaatctc caaaggcaga atatattacg ttggaaatac ccaatttgga cttacaccaa 266220 tttcatgata aatagcatct ttccatttcc catcaacagt ggccatcaga aaagtaatgc 266280 atttcataga aacaatattt taagttgacc ttgtgtttag tgtccatttt tgtgtcttaa 266340 ccccagatca agattcccat gagtaaatct attcacctag aacgaagagc cacggactct 266400 cattcacatg tccatccatc cccttccctt gcatacctgc ccacgcatac ccacaccgaa 266460 tgctctatac ctctgctaca agccttgtgc cagctgagga caggcatgtc ataaacacct 266520 cctggtgaaa taggaaactg aggcagcatg tggaccattg aaacgagaga gcagagttcc 266580 agtctgggcc agcactgtgt ctatgaccca tcccagctgg gtttcacatt gggtagcatc 266640 aaaggagggc agttggcatt gtaagcagat aggggtgtgg gagagtttac cctgaatttc 266700 agtagccaac aaacagaagt caaaccagaa acacttgctt tgctcagcat ttaagttttt 266760 gaatgaggaa aatggccctt ttccattgta tcttgaaaag cgttgttccc tgggaaaacg 266820 ctcccaaagt tttcacacct tttgatgatg gcaacttaaa tgttcaattc tggacttttt 266880 ttttttttaa ataagaaatg ccctctcgtt ggggcataag ctctcacaac agtgtggcag 266940 gatggctttt cttaacacag aaccatagaa attagagcag aggggagact aactattagg 267000 taatttcttc cctgccccat ttgtggaggt ttgtttccta tagcaaattc tcctggtgtt 267060 ttgtccagca aggttgaaat gattcaagta atggggcttc cagtagggac atatggttat 267120 tttatccagt tagcatgttt ctttcacttt gcctataaac tggccggtca cagaaattgg 267180 atctgcaggt aggtgactct ggatcttgag gggatcttgg ggtttaaata atgtgggttc 267240 tgtttgtaaa gattttgtgt aaataggttg cacaattata taaagtattg cttccaacaa 267300 acatctagtc tgttttatgt caaatgtgaa tcactgatga acacgtgaac cctcagatat 267360 tttgtccaaa gcacagatga ctctctcaaa gataggaaac tgatggtttg tgtcctagtg 267420 tgacagtcac aaatttccaa aagacctttt tcctccctct gatgaaaatt tcattcaagt 267480 aatgctttta agtagaaatg acccaagaag gaaaaattat gtatctttgc ttttctgcac 267540 ttcttcctgc tctcatctta aattatatcc tgcccaaaca taaaggtata gctgaagttc 267600 acagttagcc aaacataaag gtatagctga agttcacagt tagtgctgag ccatttgtgt 267660 tttctatagt aataatcatt actattattc aaacataaaa gctctaccct ttcttcctgt 267720 cctgtccaaa tggcaaaatt catgggacta cttagaccat gagcagataa attattggag 267780 ttcagacttt ggtattacag aattttgggg atgtttattt taattaaaag tcctaaggaa 267840 ataaagtttg gtgtccttgg tataatgttg gttgacaatc actttacatt aaaacaaata 267900 acaatcagct catatcatct gtccctgttt ggcaggcagc gattcttgtg gctgctttgt 267960 ttcaggaaac tgaaagatat tttcaggcta aaaaattttg cttggcaccg tagtccagta 268020 atcagagtta gggctagaga ctgacactgg ggactctagg ttatcttatc ttattaaaat 268080 ctgttggaaa aagtttaaag attccaaata atctctgctc ctatgttaat tcccagaaac 268140 taaaatgttt ttaatttagc tgacatcagc tgtaaggttt ccatccacaa tattaatcaa 268200 actgactttc ttccatcctt ccagaaaaat gttttttgag atacaacgtg cataccatta 268260 attattttag tttcaaatta tttggtaaaa tgctttaggc aggataaatc atttccacat 268320 gatttgtttt aaatttataa aggattttct taaaagttaa ttccattttt atgtcttttt 268380 ttataataat ggtgattcca ttaatatttg aaaattcttc attcagaact gaatttaata 268440 tgcttattaa agtaatagga tttcaacagt tcttttttat caataaagaa ttttatatac 268500 tgtaaaaatt ggatacttga aaacatctca agcaaataat catctaatat tgatatcaat 268560 agaaataatt ttatataaac acatatagca tacatgttta tacaacatat aaacattcaa 268620 gtatgtatga taacgtgtat ttcctcaaat ctatattatg agcttagtgc taaagttttt 268680 atctttccat attcatcact cttaggcaaa aatgacagct aaaggaaaca gtcagttgct 268740 tttttaaaac agtcactaat cacaggaaat gttaatatag gaatttacta tttctttcca 268800 aatggagact ctaacagaag aatgcgaagg aatagcacaa tatattacgt gtgtcaaaat 268860 tttaaagata ctctgctaga atattcatat tttgcagtat ctggctacaa atatggcttt 268920 gcttcatttt cagttttcca gacattctct ttgattcata tcatggctgt acgtgctttg 268980 tttggttttg gaaggatttt gtttggcttt ttcaatattt ctccttcgtt atagcttcac 269040 aagttggcta aagactgagg aaggggaagt attcatcttt aaattctagg ttcaattaac 269100 aattacaaat gtcagaaaca agatcactac ctggcctaac aactgtaagc atcacgcaac 269160 caacattctc atttcactca ggagagaaaa acagtgcaag ctgataagtt cacattagta 269220 agcacatctt ctgctggaat ataaactgga aacatctctt aataaagaaa gaaaaaggaa 269280 agtaagagtt tttttcctta tgtaagtctc ttcatctaga aactttacaa acagtaatac 269340 atccctcctc ccaaaatatt gaaagcccat cattttcata ggtgtctgat tgctgctcgc 269400 acacctttca tttctgtttc caaatgcaag gctttacaaa agaaatattg cttggtccag 269460 atggccttct agaagcctcc ctgagagaac tcaggagaag tttctctagc caaaaatatt 269520 gtttccgctt attcaagtgc cagaaatccc actgccactc tttcacgcag atcaaataaa 269580 ccatctaaag acgtggttgt tgtctttgtc aactgaaagg gttgattcca ctattagaca 269640 acagtgtatc ctcccacacc catccagccc acgacccaca gccttccctc tggatttatg 269700 agcaggaaca cgaaaatcag agctgagagg tttgtagtga aaatgaaaga taaagggaca 269760 taactctgtt ttagagattc ttagtaattg cacttttctc tttatttccc tgctcattta 269820 acattttcag aaagatcggc cataattttg atttttaaaa gtccagttct tagaaaatct 269880 gagtctgcca atgatgactt taagattgga tggattaaca caaaattgcg aaattttaaa 269940 catttaaagc aaagtaatga attgctacaa agtattgaaa tcatatcata ttctatttca 270000 cttttttttt tttttttttt tttagtggca aatggctggt ttggtattag aagataagag 270060 tgtttttaat aggccgggtg cagtggttca cacctgtaat cccagcactt tgagaggccg 270120 aggtgggcag atcacaaggt caggagtttg agaccagcct tgccaacata gtaaaacccc 270180 gtctctacca aaaatacaaa aaatcagctg ggtgtggtag cgggtgactg taatcccagc 270240 tacttgagag gctgaggcag gagaatcact tgaacctggg aggcaaaggt tgcagtgagc 270300 caagatcaca ccactgcaat ccagcctggg tgacagaaca agactccgtc tcaaaaaaaa 270360 aaaaaaaaaa aaagagtgtt tttaatgtag attaaatcgg acaatgtttt aaattgtttg 270420 ctttgtcctt aatttataac acactcttaa ggatatttta atcaaaatat tctttatcca 270480 ggttcatatt tttccgggtt ttatttgctc aattttgatt ttaaatatgt cattatttta 270540 gctggatgaa atctcagaaa tcttttagtc agatgccttc agtttatgac ttaatgcaca 270600 gaaacccagc aaggcttcag aagctgccca gtatcactca cagccaaggt ggagagaggg 270660 ctgcgagcag aattcagggc ttagtttgta agtaaagata tggaatatca taaatgtgtc 270720 ttcagttgaa tattacagtg aatacccaca ctcatgacca aaacgagata gagccttaaa 270780 tgcactcagt cacaatcaaa atctggattt gggtagttcc aatgtatgtc ttttcttgag 270840 gataagcaga aaccaatgag gaaagagaga aaccagggtc tccacgtgcc gttccccaca 270900 cgcctccctg ctcagtgctg ccctgccctc atcccccagc cctgccccag gaagccttct 270960 aggctctgtt cactgcaaac cccacttcac atcattagtt atcagtcgtt cagtctccca 271020 acatagattg gaaactccca gagcaagcct ggggagcctt tggcagagag gccatattta 271080 ctccaaagcc cagtgtcatc tcaaggacat caaaggacag gtccccagag tcacactctc 271140 agttacacct gtgaccacac acaccccatg gtgttcagtg cctatggcag caagatcgaa 271200 gtgatggcca ggagaggatc attttgttcc ttggacacct ttccctctct ttcctcttcc 271260 tgtatttctc cctctaagga tggatgggtc tgtgtgtgta tctttctgtt ccaccctcat 271320 tttccttgcc ctgaattctc catttcctct ttttctttac atctttttct ttctcactac 271380 atcatctcca caccccaggc catccctcac cttctttcct gtagctaatt acattagaga 271440 ctttcagagc attcttttat ttatttattt tttggttgta ttaattaaag aattttgtaa 271500 ttcttttttt tttttttttt ttttttaaga cagtgtcttg ctctgccagc caggctggag 271560 tgcaatggcg tgatctcggc tccctgcaac ctccgcctcc cgggttcaag tgattctcct 271620 gcctcagcct cctgagtagc taggattaca ggcgcacaac atgcctggct aatttttgta 271680 tttttagtag agacggtgtt tcaccatttt ggtcaggctg gtctcaaact cctgacctca 271740 tgatctgccc acctccgcct cccaaagtgc tgggattaca ggcgtaagcc accgcgccca 271800 gcccagaatt ttgtagttct ttttatactg aattttatta aaaatacaaa gcaaccattt 271860 ctataattgt cttttttttc ccccacttta ggtcagtggg cctcaaaaaa aaagtgaggc 271920 aatttcttac cactacctta gggaataaag aattctctct accgtagcac gcacctccct 271980 gcagcatctt gggcagaaat aggtacacga aacacattta gtaaacatta tttagctaac 272040 tggtttccaa attcctgaca atgctaaaaa aaaatttatt agatgtactt ttaacagtat 272100 atatgacata cttctgctgc cttctagaaa aattgaaaga agatgtttcc atcaattatt 272160 tcatcagttg ttattcatca attgtgcttt gaaaaaatgt accagtattt tagtaaatct 272220 ttcagtctct tctagttaat gttaactcat taaatctgtt ttccaaagaa agaataagcc 272280 tgcattattg gtcttagcta caaactgcta taaatggcat tcattgtttg cttttctcat 272340 aggcaatagg agcttaaatt tgatgtcaaa catttttaaa taaagacatt taaacatttg 272400 gcatgttaca catttgtctt ggttttaaaa ataattttta aaaatcttta aagaagattt 272460 ctggtttcaa aaagaaatct gagatggagg tgatagtagc ggaactctac ataattacta 272520 aaaaatcaat gacttatgca cgtacaatgg gtggatttta tggtatgcaa atcgtacctc 272580 aataaagcca ctttaaaaat tgagaaaatt aagcacaaaa cctaatttga tggcaaatgt 272640 gttaactccc ttagattttg atacacttgt aaatccaatt gtcttcacct caatacatag 272700 ctttctacat agcatacttg gctttatttt tccagatttc cttgtgaaaa gatatcgaaa 272760 acaaagactt gcctactctt gcctgattat tctgcctgaa tatttttaaa gagaaatctt 272820 gccatctaca tgtttagacc ccgaggaaag ttttaaaaat agaaggctac cttggtctct 272880 cggatcagcg tttaaagtaa gcatggctct ggtccgtgga gacccagacc tgggcaagta 272940 gatgattcgg gatggtcaca tatgcagata actggcacac acatgcacct cagctctcct 273000 ccctgttgtt cagccgcctc gacctttcct gccctgctcc tgccaaatcc atcttccaag 273060 ccttctactg cttctccttc cccattgcac ccccgacttc ctggaactct tggtaaagtc 273120 ctgaattagt cttgccaaga acaacacaca aatctttcta ttttctagcc ccatctttcc 273180 atttatttag ctaaagctaa ataatttcat cctgcctttg taaaaagcag aatgttaacg 273240 ctgtctattc attttacatc cactcaattt ccacattcca agaaatgtcc tcccttttga 273300 acaaatgtgt ctagctatca tctttgctac acctcttcct tttctggtcc atcatctgct 273360 gaaagaacgg tgtcctgcgt ttcagtacct cctcctccgt gtaagccaag ctctggactt 273420 cagatcatct gcatttgatt agcgtctgtc ctctgctgat attctaagtt ttttaatttt 273480 tctaaattta tttgttttcc tcctgaggcg ctgccaaata tatagcatcc ctgagtctag 273540 tttcttaagg agacaactaa atctatgatt tataagagtt tagaggggac aggaagcttc 273600 aggcatgagc ctgtttctat tcattgtatt ttcaaaaaca ctgatgtttc tcaaactctt 273660 gcaggtctta aaactactct gaaatcataa aacccactta gaattcaaac agtctgcttc 273720 tcactgggcc attctgtgat aagtggaatt aaataatctc tggccagcaa taacagtagc 273780 aataccagta gcaatggtgg tagcagtaac catgtgtgcc gtggtcatgg ggctggtaat 273840 aataaccaga ggagagatca tcatactcct aacagtagtg gtggccatca tgacagtggt 273900 gtggccacag tagtgacagt gctggtagca taactgcttc catttatata tatataaaac 273960 atattccata tatgtgtgta tgtatatata tatatatata tttttttttt tttttttgag 274020 acagagtctt gttctgttgc ccaggctcga gtacaatggc gggatcttgg ctcactgcaa 274080 cctctgcctc ctaggttcaa gcgattctca tgcttcagcc tcccgagtag ctgggattac 274140 aggcgcatgc cactatgccc ggctcattgt atttttggta gagacggggt ttcaccatgt 274200 tggccaggct ggtctcgaac tcctgacctc aagtgatctg cccgcttcgg cctcccaaag 274260 tgttgggatt acaggcatga gccactgcac ctggcccttg catatattac tttatgtaat 274320 cctcacagca gccctacagg ggcgatatta tccccatttt ccagatgaag aaattaagac 274380 tgggaaaggt agctttattc attgtggatc acacagctag gaaaaggcat tcctggattc 274440 aaagtcaggt gtaatggagc ccaaagtcca catccctaac ctctgcatga agctgcttct 274500 aagggaaacc cccagaaaag ccagatcctt tctctccagg gagcttcatt ccccttcatt 274560 gcagccacag gctactgaga gccacagcag gctgtgccca tcctggaaag tgtcctgttt 274620 ctgtgtggag aagatgatcc cccatgcctg ctcagaccat cactgacctg gcaggtggag 274680 ctgccccagg aacacaagag gcctcccttc cgtgcccctc atggccctgg cctctgagtg 274740 acagccagag agctacaggg gaagggacgg gagggataaa gaggagcttc ttcaggcttc 274800 tgcacctttc agagcttgga aaatgaatcc actaactgcc cagggtgcag aatcctccca 274860 acctcctgca cgacccccaa actcagcacc ctctctgaac ctgggctttc cggggccttc 274920 cccagctgct cagcatgctg ctcccgtctg gcttttcact gtgcttccca gtcaggtgca 274980 acatgaatgc caccccatcc caccccaaac ccgatattcc cactgttaca ttcttatgaa 275040 ttatttaaag ggcttctcca tcaaaggcca tggagtgtct tccgtctgaa ttccatgata 275100 ggtaaccata gattagcaca atgtgaattg gtgtctgtgt tgaatgactt cggttgaact 275160 ttcagaaatt tcatgtagag atacattagc atccgtaaat tatctggcaa taggaacgaa 275220 tggctgctga atttcaattc aaaatattat taaaataccg atgaaattat cactacaatt 275280 taaagtgtaa aaagatgaaa aacacgttct atactttcta agtctccagt catattcttt 275340 tactatcttc ctgacagttg tttatttatt taattattga gacagggtct cactctgttg 275400 ctggagtgca gtggcatgat catggctcac ttcagcctcg acctcctggg ctcaagtgat 275460 ccttccacct cagcctcccg agtagctggg accacaggtg cgtgtcacca catccagtta 275520 attttttttt ttttttttgg aaaagacaga gtctcactat gttgcccaag ctggtctcga 275580 actcctgggc ttaggcgatc ctcccgtctt ggtctcccaa agtgattaca agcgttgagc 275640 cactgtgccc agccttcatt acaattttta aagatgttta tccataaaac aaagggttac 275700 tgatattcag atgttataca aggaccaaat atcactgcct tcaatcctcc taacaactgc 275760 tttaggtgtt tttaagactt aaaatgtcac tcatatattg tattattgaa ttctagtatt 275820 tctggtattg taataaatta tagtaagaac tttcaaatgg aagcccagga tgaaaaatgt 275880 tatagtttac ttttgcccaa attctcttgt taaaattgca gtttcacgta tttgcttatc 275940 tgcacattat ctgtatgtat ttttagcctc atcttatgta ataatatttc tgaaatagtt 276000 tagatatgct atttttataa attacattaa atataattta aaatacatag tatatacaaa 276060 ataaatatgt agctgtatta gaactttata attatcccaa ataccagtta tcagccatac 276120 tttgggttac aatgattaat aagaagaatt tgagatttgg ggtaaaaagc cttagattct 276180 agtctcgtcc tcttaagttc ctttataaga ttaactagta ctgaacccca ttgtttgcac 276240 ctgtaaaact aaataatcat gccttctgta ctataggtga gaaaatgtct ttgaaaatgt 276300 tttgggccag gcgcggtggc tcacagctat aatctcagca ctttgggagg ccgcagcagg 276360 tgaatcactt gagatcagga gatcaagacc aatctggaca acagggcaaa accccatctc 276420 tactaaaaat acaaaaagtt agccaggctt ggtggggcat gcctgtagtc ccagctagtc 276480 agctagtggg gaggctgagg tgggaggacc acctgagccc gggaagtcaa ggctacgatg 276540 agctgtgatc gtgccattgc actccagcct gggagacggg agtgagaccc tgtctcaaaa 276600 aaaaaaagaa tattttgtaa tagtataaag tactatcaca tgaaacctct tttttgggta 276660 atgggtcttc ctaatagaat taccctcctc caattttcag tttggaaact aatattccag 276720 ggcttactga gggtatagtt aactagagta gaggttatag ttgccaagac aatcttccta 276780 tttcctcctc aaggaaactg acatcctttc ccctagatct acccttcccc tggcgcccag 276840 aaagctgtgc cagacaatcc atccatgctg tcccactcgg aagtagggct gggccgggcc 276900 aggccaggcc agcccagccc agctcttagc ttccccatcg ttggatcctc ggaccacctc 276960 tggacagagg aaaaacaccc agagtgaaga aaaggaaaca ggtggttcaa cttcctctgc 277020 ttagggtcca ggaaggagca aacgtgggcc catcagtgca tgtagcaaga acaggaaccc 277080 caccgggttt cagtccagct tcgtctaata gagactgtct ttatgtgctt tgtcataaga 277140 aaagtcaagc agctaataaa tagcagaacc gaccgggcgc agtggcttac ccctgtaatc 277200 ccagcacttt gggaggccga ggcgggtgga tcatgaggtc aggagttgaa gaccagcctg 277260 gccaacatgg tgaaacccca tctctactaa aaatacaaaa attagctggg tgtggtggcg 277320 agcgcctgaa atcccagcta ctcaggaggc tgaggcagga gaatcgtttg aaccagggag 277380 gcagaggttc caatgagccg agatcatgcc attgcactcc agcctgggca acagggctag 277440 actccatctc aaaaaaaaaa aaaaaatagc agaaccaata ttttaaaatg tcatctctct 277500 tccagattgc tttaatttag gctggagtag gctgcgtgtc ctcaggctct aggagacagc 277560 ttttgagcca tagacagagc cacagaaaga tccagtgtct cctaccacac cccttagttt 277620 tgtgtgtctg ttatgtcact ggtgaccaga gacacaaggc tcctgcagag caaagaaaac 277680 cgactccatg cacacttctc tgtgtcccct tccagtcccc acgcccctct cctgtctcct 277740 ggcatccctg accttctaaa gctgactttt aaatacctgt tccttgaagc ccttccctgg 277800 ccaaaccagc accattgtga tagctccttc tctctgcagc tccttggccc tgaagcacca 277860 caaacatcat aaactcactt gccctttaac tgttaagtca tttgcatgag ttaacttgag 277920 cccaagccaa catgaaaatt ctttttgtga aaaggtctca ctctgtcacc caggctggag 277980 tgcagtggtg tgatcacagc tcactgcagc cttgaccagg ctcaagcgat cttccccact 278040 cagcccaaga gtgctgggat tacactacca cactggcccc gacattacca gttttgaagt 278100 cagccatggt gtcctaccag aggctcagca agtgttggcc aactgaccag tgaatattac 278160 cagatcaggg gcacagagag acatgtgcag ataaaggaga ggaaaagggt gagctcagag 278220 ctggaaagct ttgtggagac ctggggtgat tctgtcttct cctatcactg tcccctcgat 278280 cacccagctc acgccccaga gagagccatc atgtgccctg gtctgtcttc cttccctcct 278340 cctgaccctt tcccctgctt agctgctcct cacccttcac atgtcagttt aaacatcacg 278400 tcccacagga tgccccacct gatcaggtta ggtcccctat cagttactct tcaactcccc 278460 tgtgccttgc ttttggagca aacgttctag ttcttaagta atagtcattt ctatcactgt 278520 ctatttaatg tccttcccgc cattagactg gaagccctgt gaggtcaggg accacatctg 278580 ccttgttgcc tgctgtcgta agtccctggg cctgtggcac gccaggtatg cagtaggctc 278640 tgcatccatg tcaatgcagg gagctgatag gcacaggtgt gggccagggc atcctgcaga 278700 gtttgatggg gtgggaggca gagccccata tccctgagac cagctgggat gaagcctcac 278760 tgcacattcc aggtgactta aagattcagc agggatgtgt gacagcaaag ctttgcccag 278820 acaactacag tcccttccct aaggtcccaa attaaagaaa aagagtgacc caaatcacca 278880 actaccgaac ttgtgtcctt ctattcaggt aggtcggtat tgctgctctt ggctttgcat 278940 tcagcctttt ccatcatcac caggtcagcg gtcacagagc atctcccgtg tacctggcag 279000 gtactgggtg ctgggtgcca ggtcctggga gtcaaaggta cgtgaggcct ggcgcctccc 279060 cacaggggcc tcacagtgtt gtgaaagaca gcaatgtaaa caaatactct cactagatgg 279120 gaacacaggc tatacagaga gctgtacagg gaaagggtgg agagggattt gctctaccaa 279180 ggaggcctca aaacacttca cagaggtgac accttgacat ctggaagcat caggaggagt 279240 ttgccagaca gggaaagggc cttcagagag agaacagggc atgcggcaga gctgcagcgt 279300 ggtgtgtgtt ggggtacagg cctcagggga ctggcaggag atgaggctga ggggggaggg 279360 tcccatcatg ggcaggcttg ggtctccact gaagatattg cacttaattc tgcaagtcca 279420 aagaaaacca tggcagggtt aaagcaagtg gatgattcca tcagatctgt tttagaaaga 279480 taacagcacg ctcccaacta gaaaagtgcc actccctata aacatcctgg caccatgtcc 279540 ctgagagctc caggagccag ctttggagcc gggaagcctc actgagctga gggtgcctgg 279600 cacccaaacg gacatcctta aaatgaatgt cacaacaaaa ctgagaggga accaagggca 279660 cacgagggcc tttctaagga ctctccaagt gggagaagtt gcaaaatagg aaagaagaat 279720 gaaacagtgc ccatgagagt gtctccggga gcatcatctt ccgcctttcc tgaggagttt 279780 cagggcgctg ttgacctcgt aggtaaggag gagccgtatc ccaggaggcc acagctgggc 279840 tgagagattt agcaagtgga aggcacagcc aggatctcga ggagaaattt gatcacggcc 279900 aacactggct ggaagtttag gaattccctg ggaactgctg tgaggccagt cattcattca 279960 ttgagcagaa agacttagca ccatatggga aaagggtgat accccaaaaa aggactctag 280020 ccgctgtatt caaatattag cgttaattct cacagagaac tccctctcag gaagccacag 280080 caacaccgtc atcagaatgt gccagaagga accccttcag tatccacaga agttaatttg 280140 gaaacatagt gaatagggaa agacttagat caatttgtgg tttctagaaa attactcttt 280200 taggactatg gagaaaaaag tcaagtacta agtaccagaa atgcaaaata tatgacaatt 280260 tcccatagat gtgattacta ttgtcatcac gccatcatca tcaccttcac catcaaattg 280320 taagtcagat tatgtcagtg cttatctgat ccacgggcaa tggccgaggt gtcagaaaaa 280380 ctacagttcg atggtgactg tttccttcct acgcggaaga cacgtgtgct atggtgatac 280440 tggccttcac ctccaggagt ctgaaatcat agacatatgt atagtaagat gtgcaaagca 280500 attgaccagt gatttattac aacaaataac gccataggta actgtcaaat aaaagcccat 280560 tgcgtccgga gttccacggc aacgcgtgga gatgcctggc attgctctag gtacccaatg 280620 tcgtatctgt gtgagcagtg cagtctcgca aagatggccc tgattgggaa gaagtgcagc 280680 catggcaggc cctcagatcg tccctgtgct caccaccctg gccttttctc cgattcttgt 280740 tgcatcaggt agcacctgct tcttccttcc ctctcccctc cagcaaatgg taagctccca 280800 gagggcaggg ccaagtctca tcctctcact gtcccaagtg actcaccagg gcctggcaca 280860 agggagctgc tcggtccata cttgatggat gaatggataa gtggtgacta acctaaggaa 280920 attctgccat ttggcatctt ggggatgcct tacaagagaa aggcatcatt tacagaaggc 280980 tgcaagagga ctcttcagtt tatagacctg catatccaag ccagcctaac catttctacc 281040 tgggggagct aaaacacgga agttctcaac gtgaatgtgc attagaatca ccagaggagt 281100 cctagtcaac ctctaggttt tctgcacaaa ccacgtggca ctgggcccag gaatctgcat 281160 tttaacaagt cccccccgcc cattgttctg attcaggggg tcacagaaca cactcagaga 281220 acccttttca atcaccaggc ccctaagagc acaggcttgg cattagatag agtcagcttt 281280 atccctgttc tattatatct ttactaactg cagggctaag ttgcacatgg ttcttaagct 281340 ccttctgcct cagtttcctc agttattaaa aggggatgag tacaaactca gagacagaaa 281400 ggagaatggt gctgagcagt ggctcatgcc ttgtaatccg agcactctgg gaggccgagg 281460 caggaggatc acttgagcct aggagactga gaccagcttg ggcaacatag ggaggcctcg 281520 tctctacata aaaaattagc tgggcatggt ggtgcacacc tatggtccca gccacatggg 281580 aggctgaggc aggaggatgg cctgagcctg ggaggtcgag gctgcagtaa gccgtgatga 281640 cgccactgca ctccagcctg ggtgacagag tgaaacccaa ggattctact tttgggatcc 281700 ttgtcaaaag tagaatggtg gttgttgagg gcagggggac atggaaatgg agaattgtct 281760 tatagataca gagtttcagg gatttggggt tttttttttt tttttaggat ggagtcttgc 281820 tctgttacct aggctggagt acagcggcat gatctcagct cactgcaacc tctgcttccc 281880 aagttcaagc aattctcgtg cctcaacctc ccgtgtagct gggattacag gcacccacga 281940 ccatgcccag ctaatttttg tatttttagt agagacaggg tttcaccatg ttggccagtc 282000 tggtctcgaa ctcctgacct caggtgatcc atccgccttg gcctccaaag tgctgggatt 282060 acaggcgtaa gccaccatgc acaggctgca gagtttcagt tttgcaagaa ggaaaagctc 282120 tggagatctg tagcacaatg tacatagagt taacactact gaactgcaca cttaaaaatg 282180 tctaagatgg tgaattttat gttttatgtt tttgccacaa ctaaaaagaa aaagttttac 282240 tggggttgga taatggtatc tacttcaaag tgttgttatg agcattacat gaaataatgt 282300 atgtaaagtg ccaggcaaca ggccccagac taggaactgc tcaaaaaatt atagctatta 282360 ttattacagt agcatgggtg ttaaaaaatt taaccatgag gccatgcgca gtggctcaca 282420 cctgtaatcc cagcactttg ggaggccgag gtgggcagat cagctgaggc caggagttcg 282480 agaccagcct ggacaacatg gtgaaaccca gtctctacta aaaatacaaa aaaaattagc 282540 caaacgtggt ggcacgcacc tgtagtccca gctagttggg aggctgaggc aggagaatcg 282600 aacccgggag gcggaggttg cagtgagccg aggtaacacc actgcactcc agcctgagca 282660 acagagcgag actcagtctc aaaaaatata taataaatat aaaatataat cattaaggaa 282720 gatttcaaac cctcctcaaa aatccaagta gctttttgat gaactgcatt tttctaaatc 282780 ctgaccaata gactattttt catctcacct atagacccac atgttaaaaa aataccacct 282840 aaattatagg tggctatgtg agagcctggg gatattcacg ctaggcagtc tcattcataa 282900 cactaccatc ctccatttgc agtgatgcag gaaacaagaa aaatgctaca tttcgttttg 282960 caccttaagc ttcattaaag aaaatcaagc aaaacctgcg accatagaag aaataatctc 283020 ccagtcttga aaaactacat gaagtgtttt ttatctttga tgtgcacatg gaacccaaag 283080 caggttcggg aacatggcac agactcacag ccaccgtttg gattctctgc gcaccgtttt 283140 gatttcctgt gcatctatgc taatttcgtc tccccagcct attgtttaaa ccctagcagg 283200 acagatgtgc tgttttacag ggccataacc cacttggtgg gtggataacc aagaggcctt 283260 tggtcttcat catttactcc aataagaaaa ctagacgatt gccttgtaaa acagcatgtg 283320 acccaggccc ggatttccac gtaacgccaa cctacaggac cacctcggaa cttccaacca 283380 aattaggaaa attcctcctg gtcacagagg tgaccaaaat tagctcgagg ctgaatgaaa 283440 ttatggaaag gacaatctag gggtaaaaac agtaaaaaca agagggctgg gaagtgactt 283500 acagtacagg aatttaggtt taggccacac aggtgttcat gtgagtaaga gtcatcattt 283560 ctaaggctga aaaggttggc cactgctggt aaaaattcta atcctagtag gcttagaatc 283620 tctctcaatc aaaagataaa tcccaaaagt cattgctaag gattcccccc atttttcttt 283680 acctccatcc tatgtataac cgtaagttac tacctctcag ccctcatcat gagagcccag 283740 cactcctgtc ccggcagccc tgagtgacat cagcattgac tgttgggaat tggtacttgt 283800 gaaatccaga aatgggctac aatagatgca aatggaccat catcaatgtg cattaggatt 283860 gccccagcca cccccagatc tcgaaggacc cctgcaaccc agtcacacca gcatccttgc 283920 caacaggtcg aagcagggtg gattaggatg aagggatatc atcgtaagca gcaaaaggaa 283980 gtgatgaaaa gaacacaaat aaccagacat taactttggg ttctgagcat gctgctttct 284040 gtccgtttaa tctatctttt gctgatgcac ttaaagaagc taccttgtct tcttaatgtg 284100 gggatctctg atgaaggctt gaagctctga gacccaagca tcagccccag ctctggcttt 284160 ccctagtcac atgaccttgg aagatcactt cttttttttt ccttctttta ctactctgag 284220 cctcagtttc ctcatctaaa acagggctta ggttacttga cacagtctat ataagtatgg 284280 tagaagtttt ttaaaaaatg agtctgtaaa atgggactat tccaagagat ttcagagatg 284340 ccttcccatc ttaacattca acagatctat gattcctttg ttacagctca tgtccctggt 284400 atttctttct tttttgagat ggagtcccgc tctgtcactc atgctggagt gcagtggtgt 284460 gaccttggct cactgcaacc tccacctcct gggttcaagc aattcttctg cctcagcctc 284520 ccgagtagct gggagtacag gcgtgcacca ctatgcccag ctaatttttt tgtattttta 284580 ttagagacag ggtttcaccg tgttggccag gctggtcttg aactcctgac ttcaggtgat 284640 ccgcccgccc cggcctccca aagtgctggg attacaggtg tgagccactg cgcctggccg 284700 tccctggtca ctctaatcgt cttctgtatg ggtttaccaa cagactcatc tctttgtacc 284760 ctgtacaatc ctaccttgca ttttctcata accttatcat gttacctctc aattatgtta 284820 cagcaaggag gtaagatttt gccattagcc tgatggtaca attttttaaa acaataatca 284880 gttgccagaa tatattcttg cttttaaagt tctacataat atttcaaaaa tatataggga 284940 agtatttaga ttttccttcc acagctgttt tctgcttgat ttcaagagtt aactgaacag 285000 tttgctgtct tgtgtccaat gtgtttctcc tctccattaa aatgctgaag atttttattt 285060 ttttcccctc tttaggggga aaaaagaagt gtttcctctg taatttactt tggctttctc 285120 aaaagttggg cgggaaagtc agtataattc aggtggaatc taaaatgttc ttgttgcaca 285180 agtgtgcaca gaaaggaaac ctataatttc gagtattctt tcaggaagtt tgtattctct 285240 gttttccagg gggcctttac tttccaaggg agtatgatcg acatgccatt actgaagcag 285300 gcccagaaca ctgttacgct tgccacctcc atcaaggaaa aatgatctgt taaatgaagc 285360 tgtcatcagg tgggctgaac atatacagtg gggttcttaa agacaaacca caatactcaa 285420 agcaacttgt taggatgcca gattgggacc tgactccatt tacagttcat gttaatcaca 285480 attttgttgt tgttgtctca ctggccagtt attcccctaa aaaaatgaac gcttttccct 285540 ttggatccaa gcttatgatt ttatcatttt tagtgtatta cgaatatggg cttatgattt 285600 cacagggagg taagatcctg gggaaagatg ggctgtgagg cgaaggtagg tctttaatga 285660 aatggatctt tcccaaatag acatattccc tccacccttc tcatgttagt aaatgtttcc 285720 tgcttgttca tttatacagc tgacaccaca aataatttta agaaaagcca ggcctttaaa 285780 acatagtagc aacattaagg ggtcatctct atttcactag taatctgata aaacaacaga 285840 gatggcatca aaaaagaata ctaagtatta tattggctta aaaagacact ttctgaaaat 285900 aaactttcga aactggttac tattaacctc cacccctaaa acgaaacatc catctccttg 285960 aaccgctaga cgatgaacac gaaagctgtc atcctgggtg aatgctgtga gtcaaccatt 286020 accggcaatt aaaaaataaa tgtgcagaaa cacaagacca tccattctcc ccctttattt 286080 tcccgtttaa ctgtttgcca ttgaggctat ttccccctgg aaatgtatgg ctgggacagg 286140 actccctcag tcataaactt gtagcgtctc agaagacaca atgcacccga gctggtgcat 286200 gtggcccctg cgagatttgc atcacattag agatgcggct gcaggtcaga tgggtggtgt 286260 ggttaacggg cttagtaaag ctgttttgaa gaggttaacc cagcttgtag taagggtaaa 286320 taaacataac aaccagccat tgttccctat tcagcatgta ctcttatatt gaaggctaaa 286380 gggtattgaa gctgcagagg gatcaacttg tgcttgccag aggacgccaa tgaagtttga 286440 aacaccaaca atcagagatt ttgtttctgt tcctcattaa atcatgagct tttgtgccga 286500 gactctggac gactgttcct taagaaatta acagaatggg aagttttaaa ctctacacca 286560 accttttcat gacctacaca gcagcaacgc tgctactctt agacaaacac cgcggggaag 286620 gctgttctgt ttatttaaat ttgtaaatag aaaacagttg ttttttactt tcatttttca 286680 cctcctccta cgcccttttg gattatttcc tctgcggccc ctagcatgag ccccaaccag 286740 gcctcccctt ttccccactt ctctcaattc ccacaggaag cccgagaggt gaggagctga 286800 ggttagacac caggagaggc accatcacac aaaagcgcgg ccgcagagtc ccaccgccac 286860 caggcgaccc ccacccagag agggacagac atgcggggag ccagcaccgg gcaagatggc 286920 tctggggatc ctcattctgt gaagacacca actcatttct caaacacagg atccaggaga 286980 cagatagctc ctaaatggag atggcacatg ctccgtgggg tccctcatag aggagtgcca 287040 ccctccacac tggccacgct gggctgcccc agagcggcca gaaaggaagg tgggagctag 287100 ccccatcctc actcagaggc cggaaggagg aagatggcat ctcgccaact tcagagccga 287160 atggcctcta gccacactgc ttccagaccc cagacggggc agcagcagca gttcccagag 287220 gagcacccat tgttgcagct aggacccacc aaggatggga ctcctggagt caggtgcaca 287280 ccaggtaacc caggaccacg ctgtgcaccc ccagtctgcc cctctgctca gaacacagag 287340 ggatgggagg atggcttggc agtgggaagg caaaagaagg cctctctcac tctgcccctg 287400 ccatacgcac ccgctgaggg tgttagaagc agtggaggca gagctggccc taagcaaaag 287460 aagaaaataa acctcacctt gtccttccta tgggcagccc tcaccccaat ctaactaacc 287520 ttcccatcct ccagcctaat ccaaagaagc ccttggcttg aggggatgaa gggcttgcgt 287580 tctagtctcc accccagccc cacaggcagc cagccagcca gccccacaca gaggggcctc 287640 ctcaaggcct cactgggagc ctcctgtccc cagccaagga gccctacaga cctggggaaa 287700 agcaggcccc tccgcaaggc ccctgggtgg tgcggaggcc ggaccggcta ggcctcccgc 287760 tgctggccac tcccaggcca cgggttccta ggtcccaacc acattggact gctcgccacg 287820 ccactgccct catcccaaac tgctttgttc aaacaaaacc accttgtttc agtctcccca 287880 aatgtccagt tcattatctt cctcataacc catggtccct attagggtag gatcatgaga 287940 ctaagaccta tgagagccac aaatctggac caaagtccca ttccctgaac agagacccaa 288000 acgacgaggg tcccagaaga gagttcagtc ctgatcagaa acccatggtg ccttagtcct 288060 tgaagaacaa aactctagga agaagatgct ggaaggcaaa gggtattccc cctctttccc 288120 cacccgcgtc tctgtggtgc catgggtggg cccaggtacc ctgggaaagg tgggagagca 288180 gtcaagggtg ggtgtgtgat ctccactggg ctcactgggc acccccgaca cggggaagtg 288240 agagctgccc gactcctgag ccaggcgtgg gtgacaggaa gaggaccttg cagctaatct 288300 gattcattag aaaccatacc tgtttatgtt ttgtgtagct catcacaagc cgcttagcca 288360 tatcaccccc gttattaatt cttggggtct aaattatggg taacactatt aaaacattat 288420 cagaactaat gagaaacaat tacttagaaa atgagccggg acaagactga gttgggaaca 288480 tcagtggtga tcactgtaga ttagtttaat aaatcatcag gtgcaaggca agactgactg 288540 tatgtatgca aagccccgtc acgggaaaat gaaattgaga tttttttttt ttgcataatt 288600 ttttcattaa tctcaatagg acccgtgtgg tgtagattgc tttattcccc taataccttg 288660 cctgaggcgg gggggggggg gggtgcccaa taatgtcttc attgttttac tgaggtctta 288720 atgacaatct gtgacaacct cattttaatg tatagaggat tatatcaata cagtcatgtt 288780 ttattgaaat ggtgaaggga actccagtca gagtcaggca gtgtctgtga gcacaagtta 288840 ggaagtttct cggcatccgg gagcgttccc gtctgatgtc ccagtgttag tcctcccggc 288900 cgccctcccc tcctctcctc cagggacggc tgggaaaaca gtcctgcggg atgaagactt 288960 caccgcctcc gatttgaatt tgaaagtaac tccttccgtg gcatatttcg ctgggcagat 289020 agaacaaacc atgtcgtttt cccccgtctc taaaatagac atattattat cattcacact 289080 tttgcacccg gtcgttttgc gggagttcgg gaaactgact ttcttcattg gggacattgt 289140 aattttctga tgatgccacg aggagaaaaa aaatacgggt ttgttttaat tggaaggacc 289200 ttccgctttt atgatttcgg tttaccttgg aaaactgaat cttctgtgtt ttatttcttt 289260 cctctagtac tagaaaagca atgaattaat tgcacaaaac aggttctgag acggcccgca 289320 ggccccgagc tcgtggacgc ggccgagggt cgggtgtgac ccgcggagcc gctgccaggc 289380 ttcccagctc gtcttcgcgg ggaggcggga ggcaggacca gaccccagca tttcagcgtg 289440 aaagtcttcg cctttctttc cgcgctgtct ttcccgcggg cggagcggcg tacctgagcg 289500 cggtccccac ggaggatcag tgactttccc agaccccgcg ggcgagcccg cgcttgggac 289560 ccggcagctc tgcgcgggct ggttttggag ggggtggtgt tcgtttgttt aaattccagt 289620 tgttatttgg cagcatatcg ccttccgagt cagtaagaat tgcccacgac gtaaagagcg 289680 acttgcagga aggggccgaa gccgtcgtta gcgcccgggc ggcggcggcc actcgaaccc 289740 cgtttccgcc aagcgcgctg caacctgcgg ggcgagttcg ttttgttttg ccaaaatcat 289800 ttggggactt ctttgtcatt catgcccttc cttttaaatg atttttattt ttttccactg 289860 taagtgaccg gctgggtttg acttttgctt cttccgacgg aagggcaccg cgagccgggg 289920 tgggcggccc cgcgggcagg aggagcgcgg ggtacacgcg gtggccgcag acgccgagcc 289980 ctgcggagcc ccgaggcctc gtcgcccgcg cccccggtgc gcgcggagcc ggggccgagg 290040 ccgggccagg aggagtgtgg cggcccagga ggcctggact gtgggccctg ctcgcccgcc 290100 cgccgcgggc cgcccggagc ccgcgcgcct gtcgcgcagc ccggctgtaa tggtggcaga 290160 tcaaaggcgg ccccgtgtcc ccgcggagcc cgggacaatc ccgcgccttt gtgcgctgtt 290220 gctaggagcc cgagaaacta agagaaagtg tcaggagcat gttaatcaga ctcgttacac 290280 tgtaacaata acgtctctct cgggtctccc aggccccagt acccccgcgc accctgcgcg 290340 caggccggac acctgcgcag ggcccttgcg cccgccctgg ggtcccgccg gccctggggt 290400 ccctgcagcc ccgaatccgc acccgagcca cgcggaacga ctagccccga ggggccccgc 290460 aggctcccgg tgcagctccc tggtcgtggt ctccttgacc gaagccccgg cctcacaccg 290520 cctggccgcg agcccgaggg acgcagggac gatcccggtc ccctgctttt cagtcctcca 290580 gtcgaatcgc ccactttgtt caatcacagt attcgaatca agaggaaaat gaacattccc 290640 tttatggtag ctttttggtt atgagttttg gcaaaactgt taaatcaact ttgccgattt 290700 cccttgggaa tccctggagg ccactctaag tggtaatccc aagtttaaga aggaaatggg 290760 gaaattttgc tgagagtaaa gatgtcgccg aactttttga agggatttgc ttcattcatt 290820 catttagtca ttcaacagac acctgttgaa cccgactggg tgccagaggg gccagtcaca 290880 ggacttattc cagatgaact tttcttttga aattagaatg cccttgtgga agccaaagga 290940 ggagcagagg cctaaaataa tgtcaagtgt caaagcaaaa agaagtgcca ttggctacta 291000 cagtgtgtga tgataacaag agaggtgcga attaggaatt aaaaacgttt gaaaaactac 291060 aggccatatg ctttgaaacc agccactttt tccatctttc atctccctct cccctccggt 291120 tttggtgggc aggagctatg ccaggctgca gtcctcaacc cgtcagaggc ctgcctgagg 291180 tctgaggagt gaggccaggc cttctgtttg tacacagcct ttcaaacgtg cagagagaca 291240 cactccatcc tggccccatt ccccctttgc tcatacgcag ggaactggaa acctgtcctc 291300 aagattaggg ctgaatttgg ccaagttaag gtgcttttct cccatacaag ctcttgttcg 291360 agaacaaacc cattctggaa ggtatagaag ggggccagac ttccagagtc aagctacccg 291420 cacctaagtc acaggacaaa gctggctgtc accaggatgg gtgtaagaca gcctctcaac 291480 tcacctgtgc ctaccattga ctgaggagga atcccaaaac tgtgtgagac tcctctgtcg 291540 gtgaaacttt ctctctttca ccgttgcatg caacatgtaa acatatagaa aactgggtcg 291600 ggtgcagtga cttacgcctg taatcccagc actttgggag gctgaggtgg gcagatcact 291660 taaggt 291666 <210> 25 <211> 12613 <212> DNA <213> Homo sapiens <400> 25 gaaaatcccc actaagatcc tgggtccaga aaaagatggg aaacctgttt agctcacccg 60 tgagcccata gttaaaactc tttagacaac aggttgtttc cgtttacaga gaacaataat 120 attgggtggt gagcatctgt gtgggggttg gggtgggata ggggatacgg ggagagtgga 180 gaaaaagggg acacagggtt aatgtgaagt ccaggatccc cctctacatt taaagttggt 240 ttaagttggc tttaattaat agcaactctt aagataatca gaattttctt aaccttttag 300 ccttactgtt gaaaagccct gtgatcttgt acaaatcatt tgcttcttgg atagtaattt 360 cttttactaa aatgtgggct tttgactaga tgaatgtaaa tgttcttcta gctctgatat 420 cctttattct ttatattttc taacagattc tgtgtagtgg gatgagcaga gaacaaaaac 480 aaaataatcc agtgagaaaa gcccgtaaat aaaccttcag accagagatc tattctctag 540 cttattttaa gctcaactta aaaagaagaa ctgttctctg attcttttcg ccttcaatac 600 acttaatgat ttaactccac cctccttcaa aagaaacagc atttcctact tttatactgt 660 ctatatgatt gatttgcaca gctcatctgg ccagaagagc tgagacatcc gttcccctac 720 aagaaactct ccccggtaag taacctctca gctgcttggc ctgttagtta gcttctgaga 780 tgagtaaaag actttacagg aaacccatag aagacatttg gcaaacacca agtgctcata 840 caattatctt aaaatataat ctttaagata aggaaagggt cacagtttgg aatgagtttc 900 agacggttat aacatcaaag atacaaaaca tgattgtgag tgaaagactt taaagggagc 960 aatagtattt taataactaa caatccttac ctctcaaaag aaagatttgc agagagatga 1020 gtcttagctg aaatcttgaa atcttatctt ctgctaagga gaactaaacc ctctccagtg 1080 agatgccttc tgaatatgtg cccacaagaa gttgtgtcta agtctggttc tcttttttct 1140 ttttcctcca gacaagaggg aagcctaaaa atggtcaaaa ttaatattaa attacaaacg 1200 ccaaataaaa ttttcctcta atatatcagt ttcatggcac agttagtata taattcttta 1260 tggttcaaaa ttaaaaatga gcttttctag gggcttctct cagctgccta gtctaaggtg 1320 cagggagttt gagactcaca gggtttaata agagaaaatt ctcagctaga gcagctgaac 1380 ttaaatagac taggcaagac agctggttat aagactaaac tacccagaat gcatgacatt 1440 catctgtggt ggcagacgaa acatttttta ttatattatt tcttgggtat gtatgacaac 1500 tcttaattgt ggcaactcag aaactacaaa cacaaacttc acagaaaatg tgaggatttt 1560 acaattggct gttgtcatct atgaccttcc ctgggacttg ggcacccggc catttcactc 1620 tgactacatc atgtcaccaa acatctgatg gtcttgcctt ttaattctct tttcgaggac 1680 tgagagggag ggtagcatgg tagttaagag tgcaggcttc ccgcattcaa aatcggttgc 1740 ttactagctg tgtggctttg agcaagttac tcaccctctc tgtgcttcaa ggtccttgtc 1800 tgcaaaatgt gaaaaatatt tcctgcctca taaggttgcc ctaaggatta aatgaatgaa 1860 tgggtatgat gcttagaaca gtgattggca tccagtatgt gccctcgagg cctcttaatt 1920 attactggct tgctcatagt gcatgttctt tgtgggctaa ctctagcgtc aataaaaatg 1980 ttaagactga gttgcagccg ggcatggtgg ctcatgcctg taatcccagc attctaggag 2040 gctgaggcag gaggatcgct tgagcccagg agttcgagac cagcctgggc aacatagtgt 2100 gatcttgtat ctataaaaat aaacaaaatt agcttggtgt ggtggcgcct gtagtcccca 2160 gccacttgga ggggtgaggt gagaggattg cttgagcccg ggatggtcca ggctgcagtg 2220 agccatgatc gtgccactgc actccagcct gggcgacaga gtgagaccct gtctcacaac 2280 aacaacaaca acaacaaaaa ggctgagctg caccatgctt gacccagttt cttaaaattg 2340 ttgtcaaagc ttcattcact ccatggtgct atagagcaca agattttatt tggtgagatg 2400 gtgctttcat gaattccccc aacagagcca agctctccat ctagtggaca gggaagctag 2460 cagcaaacct tcccttcact acaaaacttc attgcttggc caaaaagaga gttaattcaa 2520 tgtagacatc tatgtaggca attaaaaacc tattgatgta taaaacagtt tgcattcatg 2580 gagggcaact aaatacattc taggacttta taaaagatca ctttttattt atgcacaggg 2640 tggaacaaga tggattatca agtgtcaagt ccaatctatg acatcaatta ttatacatcg 2700 gagccctgcc aaaaaatcaa tgtgaagcaa atcgcagccc gcctcctgcc tccgctctac 2760 tcactggtgt tcatctttgg ttttgtgggc aacatgctgg tcatcctcat cctgataaac 2820 tgcaaaaggc tgaagagcat gactgacatc tacctgctca acctggccat ctctgacctg 2880 tttttccttc ttactgtccc cttctgggct cactatgctg ccgcccagtg ggactttgga 2940 aatacaatgt gtcaactctt gacagggctc tattttatag gcttcttctc tggaatcttc 3000 ttcatcatcc tcctgacaat cgataggtac ctggctgtcg tccatgctgt gtttgcttta 3060 aaagccagga cggtcacctt tggggtggtg acaagtgtga tcacttgggt ggtggctgtg 3120 tttgcgtctc tcccaggaat catctttacc agatctcaaa aagaaggtct tcattacacc 3180 tgcagctctc attttccata cagtcagtat caattctgga agaatttcca gacattaaag 3240 atagtcatct tggggctggt cctgccgctg cttgtcatgg tcatctgcta ctcgggaatc 3300 ctaaaaactc tgcttcggtg tcgaaatgag aagaagaggc acagggctgt gaggcttatc 3360 ttcaccatca tgattgttta ttttctcttc tgggctccct acaacattgt ccttctcctg 3420 aacaccttcc aggaattctt tggcctgaat aattgcagta gctctaacag gttggaccaa 3480 gctatgcagg tgacagagac tcttgggatg acgcactgct gcatcaaccc catcatctat 3540 gcctttgtcg gggagaagtt cagaaactac ctcttagtct tcttccaaaa gcacattgcc 3600 aaacgcttct gcaaatgctg ttctattttc cagcaagagg ctcccgagcg agcaagctca 3660 gtttacaccc gatccactgg ggagcaggaa atatctgtgg gcttgtgaca cggactcaag 3720 tgggctggtg acccagtcag agttgtgcac atggcttagt tttcatacac agcctgggct 3780 gggggtgggg tgggagaggt cttttttaaa aggaagttac tgttatagag ggtctaagat 3840 tcatccattt atttggcatc tgtttaaagt agattagatc ttttaagccc atcaattata 3900 gaaagccaaa tcaaaatatg ttgatgaaaa atagcaacct ttttatctcc ccttcacatg 3960 catcaagtta ttgacaaact ctcccttcac tccgaaagtt ccttatgtat atttaaaaga 4020 aagcctcaga gaattgctga ttcttgagtt tagtgatctg aacagaaata ccaaaattat 4080 ttcagaaatg tacaactttt tacctagtac aaggcaacat ataggttgta aatgtgttta 4140 aaacaggtct ttgtcttgct atggggagaa aagacatgaa tatgattagt aaagaaatga 4200 cacttttcat gtgtgatttc ccctccaagg tatggttaat aagtttcact gacttagaac 4260 caggcgagag acttgtggcc tgggagagct ggggaagctt cttaaatgag aaggaatttg 4320 agttggatca tctattgctg gcaaagacag aagcctcact gcaagcactg catgggcaag 4380 cttggctgta gaaggagaca gagctggttg ggaagacatg gggaggaagg acaaggctag 4440 atcatgaaga accttgacgg cattgctccg tctaagtcat gagctgagca gggagatcct 4500 ggttggtgtt gcagaaggtt tactctgtgg ccaaaggagg gtcaggaagg atgagcattt 4560 agggcaagga gaccaccaac agccctcagg tcagggtgag gatggcctct gctaagctca 4620 aggcgtgagg atgggaagga gggaggtatt cgtaaggatg ggaaggaggg aggtattcgt 4680 gcagcatatg aggatgcaga gtcagcagaa ctggggtgga tttgggttgg aagtgagggt 4740 cagagaggag tcagagagaa tccctagtct tcaagcagat tggagaaacc cttgaaaaga 4800 catcaagcac agaaggagga ggaggaggtt taggtcaaga agaagatgga ttggtgtaaa 4860 aggatgggtc tggtttgcag agcttgaaca cagtctcacc cagactccag gctgtctttc 4920 actgaatgct tctgacttca tagatttcct tcccatccca gctgaaatac tgaggggtct 4980 ccaggaggag actagattta tgaatacacg aggtatgagg tctaggaaca tacttcagct 5040 cacacatgag atctaggtga ggattgatta cctagtagtc atttcatggg ttgttgggag 5100 gattctatga ggcaaccaca ggcagcattt agcacatact acacattcaa taagcatcaa 5160 actcttagtt actcattcag ggatagcact gagcaaagca ttgagcaaag gggtcccata 5220 gaggtgaggg aagcctgaaa aactaagatg ctgcctgccc agtgcacaca agtgtaggta 5280 tcattttctg catttaaccg tcaataggca aaggggggaa gggacatatt catttggaaa 5340 taagctgcct tgagccttaa aacccacaaa agtacaattt accagcctcc gtatttcaga 5400 ctgaatgggg gtgggggggg cgccttaggt acttattcca gatgccttct ccagacaaac 5460 cagaagcaac agaaaaaatc gtctctccct ccctttgaaa tgaatatacc ccttagtgtt 5520 tgggtatatt catttcaaag ggagagagag aggttttttt ctgttctgtc tcatatgatt 5580 gtgcacatac ttgagactgt tttgaatttg ggggatggct aaaaccatca tagtacaggt 5640 aaggtgaggg aatagtaagt ggtgagaact actcagggaa tgaaggtgtc agaataataa 5700 gaggtgctac tgactttctc agcctctgaa tatgaacggt gagcattgtg gctgtcagca 5760 ggaagcaacg aagggaaatg tctttccttt tgctcttaag ttgtggagag tgcaacagta 5820 gcataggacc ctaccctctg ggccaagtca aagacattct gacatcttag tatttgcata 5880 ttcttatgta tgtgaaagtt acaaattgct tgaaagaaaa tatgcatcta ataaaaaaca 5940 ccttctaaaa taattcatta tattcttgct ctttcagtca agtgtacatt tagagaatag 6000 cacataaaac tgccagagca ttttataagc agctgttttc ttccttagtg tgtgtgcatg 6060 gaaaatcccc actaagatcc tgggtccaga aaaagatggg aaacctgttt agctcacccg 6120 tgagcccata gttaaaactc tttagacaac aggttgtttc cgtttacaga gaacaataat 6180 attgggtggt gagcatctgt gtgggggttg gggtgggata ggggatacgg ggagagtgga 6240 gaaaaagggg acacagggtt aatgtgaagt ccaggatccc cctctacatt taaagttggt 6300 ttaagttggc tttaattaat agcaactctt aagataatca gaattttctt aaccttttag 6360 ccttactgtt gaaaagccct gtgatcttgt acaaatcatt tgcttcttgg atagtaattt 6420 cttttactaa aatgtgggct tttgactaga tgaatgtaaa tgttcttcta gctctgatat 6480 cctttattct ttatattttc taacagattc tgtgtagtgg gatgagcaga gaacaaaaac 6540 aaaataatcc agtgagaaaa gcccgtaaat aaaccttcag accagagatc tattctctag 6600 cttattttaa gctcaactta aaaagaagaa ctgttctctg attcttttcg ccttcaatac 6660 acttaatgat ttaactccac cctccttcaa aagaaacagc atttcctact tttatactgt 6720 ctatatgatt gatttgcaca gctcatctgg ccagaagagc tgagacatcc gttcccctac 6780 aagaaactct ccccggtaag taacctctca gctgcttggc ctgttagtta gcttctgaga 6840 tgagtaaaag actttacagg aaacccatag aagacatttg gcaaacacca agtgctcata 6900 caattatctt aaaatataat ctttaagata aggaaagggt cacagtttgg aatgagtttc 6960 agacggttat aacatcaaag atacaaaaca tgattgtgag tgaaagactt taaagggagc 7020 aatagtattt taataactaa caatccttac ctctcaaaag aaagatttgc agagagatga 7080 gtcttagctg aaatcttgaa atcttatctt ctgctaagga gaactaaacc ctctccagtg 7140 agatgccttc tgaatatgtg cccacaagaa gttgtgtcta agtctggttc tcttttttct 7200 ttttcctcca gacaagaggg aagcctaaaa atggtcaaaa ttaatattaa attacaaacg 7260 ccaaataaaa ttttcctcta atatatcagt ttcatggcac agttagtata taattcttta 7320 tggttcaaaa ttaaaaatga gcttttctag gggcttctct cagctgccta gtctaaggtg 7380 cagggagttt gagactcaca gggtttaata agagaaaatt ctcagctaga gcagctgaac 7440 ttaaatagac taggcaagac agctggttat aagactaaac tacccagaat gcatgacatt 7500 catctgtggt ggcagacgaa acatttttta ttatattatt tcttgggtat gtatgacaac 7560 tcttaattgt ggcaactcag aaactacaaa cacaaacttc acagaaaatg tgaggatttt 7620 acaattggct gttgtcatct atgaccttcc ctgggacttg ggcacccggc catttcactc 7680 tgactacatc atgtcaccaa acatctgatg gtcttgcctt ttaattctct tttcgaggac 7740 tgagagggag ggtagcatgg tagttaagag tgcaggcttc ccgcattcaa aatcggttgc 7800 ttactagctg tgtggctttg agcaagttac tcaccctctc tgtgcttcaa ggtccttgtc 7860 tgcaaaatgt gaaaaatatt tcctgcctca taaggttgcc ctaaggatta aatgaatgaa 7920 tgggtatgat gcttagaaca gtgattggca tccagtatgt gccctcgagg cctcttaatt 7980 attactggct tgctcatagt gcatgttctt tgtgggctaa ctctagcgtc aataaaaatg 8040 ttaagactga gttgcagccg ggcatggtgg ctcatgcctg taatcccagc attctaggag 8100 gctgaggcag gaggatcgct tgagcccagg agttcgagac cagcctgggc aacatagtgt 8160 gatcttgtat ctataaaaat aaacaaaatt agcttggtgt ggtggcgcct gtagtcccca 8220 gccacttgga ggggtgaggt gagaggattg cttgagcccg ggatggtcca ggctgcagtg 8280 agccatgatc gtgccactgc actccagcct gggcgacaga gtgagaccct gtctcacaac 8340 aacaacaaca acaacaaaaa ggctgagctg caccatgctt gacccagttt cttaaaattg 8400 ttgtcaaagc ttcattcact ccatggtgct atagagcaca agattttatt tggtgagatg 8460 gtgctttcat gaattccccc aacagagcca agctctccat ctagtggaca gggaagctag 8520 cagcaaacct tcccttcact acaaaacttc attgcttggc caaaaagaga gttaattcaa 8580 tgtagacatc tatgtaggca attaaaaacc tattgatgta taaaacagtt tgcattcatg 8640 gagggcaact aaatacattc taggacttta taaaagatca ctttttattt atgcacaggg 8700 tggaacaaga tggattatca agtgtcaagt ccaatctatg acatcaatta ttatacatcg 8760 gagccctgcc aaaaaatcaa tgtgaagcaa atcgcagccc gcctcctgcc tccgctctac 8820 tcactggtgt tcatctttgg ttttgtgggc aacatgctgg tcatcctcat cctgataaac 8880 tgcaaaaggc tgaagagcat gactgacatc tacctgctca acctggccat ctctgacctg 8940 tttttccttc ttactgtccc cttctgggct cactatgctg ccgcccagtg ggactttgga 9000 aatacaatgt gtcaactctt gacagggctc tattttatag gcttcttctc tggaatcttc 9060 ttcatcatcc tcctgacaat cgataggtac ctggctgtcg tccatgctgt gtttgcttta 9120 aaagccagga cggtcacctt tggggtggtg acaagtgtga tcacttgggt ggtggctgtg 9180 tttgcgtctc tcccaggaat catctttacc agatctcaaa aagaaggtct tcattacacc 9240 tgcagctctc attttccata cagtcagtat caattctgga agaatttcca gacattaaag 9300 atagtcatct tggggctggt cctgccgctg cttgtcatgg tcatctgcta ctcgggaatc 9360 ctaaaaactc tgcttcggtg tcgaaatgag aagaagaggc acagggctgt gaggcttatc 9420 ttcaccatca tgattgttta ttttctcttc tgggctccct acaacattgt ccttctcctg 9480 aacaccttcc aggaattctt tggcctgaat aattgcagta gctctaacag gttggaccaa 9540 gctatgcagg tgacagagac tcttgggatg acgcactgct gcatcaaccc catcatctat 9600 gcctttgtcg gggagaagtt cagaaactac ctcttagtct tcttccaaaa gcacattgcc 9660 aaacgcttct gcaaatgctg ttctattttc cagcaagagg ctcccgagcg agcaagctca 9720 gtttacaccc gatccactgg ggagcaggaa atatctgtgg gcttgtgaca cggactcaag 9780 tgggctggtg acccagtcag agttgtgcac atggcttagt tttcatacac agcctgggct 9840 gggggtgggg tgggagaggt cttttttaaa aggaagttac tgttatagag ggtctaagat 9900 tcatccattt atttggcatc tgtttaaagt agattagatc ttttaagccc atcaattata 9960 gaaagccaaa tcaaaatatg ttgatgaaaa atagcaacct ttttatctcc ccttcacatg 10020 catcaagtta ttgacaaact ctcccttcac tccgaaagtt ccttatgtat atttaaaaga 10080 aagcctcaga gaattgctga ttcttgagtt tagtgatctg aacagaaata ccaaaattat 10140 ttcagaaatg tacaactttt tacctagtac aaggcaacat ataggttgta aatgtgttta 10200 aaacaggtct ttgtcttgct atggggagaa aagacatgaa tatgattagt aaagaaatga 10260 cacttttcat gtgtgatttc ccctccaagg tatggttaat aagtttcact gacttagaac 10320 caggcgagag acttgtggcc tgggagagct ggggaagctt cttaaatgag aaggaatttg 10380 agttggatca tctattgctg gcaaagacag aagcctcact gcaagcactg catgggcaag 10440 cttggctgta gaaggagaca gagctggttg ggaagacatg gggaggaagg acaaggctag 10500 atcatgaaga accttgacgg cattgctccg tctaagtcat gagctgagca gggagatcct 10560 ggttggtgtt gcagaaggtt tactctgtgg ccaaaggagg gtcaggaagg atgagcattt 10620 agggcaagga gaccaccaac agccctcagg tcagggtgag gatggcctct gctaagctca 10680 aggcgtgagg atgggaagga gggaggtatt cgtaaggatg ggaaggaggg aggtattcgt 10740 gcagcatatg aggatgcaga gtcagcagaa ctggggtgga tttgggttgg aagtgagggt 10800 cagagaggag tcagagagaa tccctagtct tcaagcagat tggagaaacc cttgaaaaga 10860 catcaagcac agaaggagga ggaggaggtt taggtcaaga agaagatgga ttggtgtaaa 10920 aggatgggtc tggtttgcag agcttgaaca cagtctcacc cagactccag gctgtctttc 10980 actgaatgct tctgacttca tagatttcct tcccatccca gctgaaatac tgaggggtct 11040 ccaggaggag actagattta tgaatacacg aggtatgagg tctaggaaca tacttcagct 11100 cacacatgag atctaggtga ggattgatta cctagtagtc atttcatggg ttgttgggag 11160 gattctatga ggcaaccaca ggcagcattt agcacatact acacattcaa taagcatcaa 11220 actcttagtt actcattcag ggatagcact gagcaaagca ttgagcaaag gggtcccata 11280 gaggtgaggg aagcctgaaa aactaagatg ctgcctgccc agtgcacaca agtgtaggta 11340 tcattttctg catttaaccg tcaataggca aaggggggaa gggacatatt catttggaaa 11400 taagctgcct tgagccttaa aacccacaaa agtacaattt accagcctcc gtatttcaga 11460 ctgaatgggg gtgggggggg cgccttaggt acttattcca gatgccttct ccagacaaac 11520 cagaagcaac agaaaaaatc gtctctccct ccctttgaaa tgaatatacc ccttagtgtt 11580 tgggtatatt catttcaaag ggagagagag aggttttttt ctgttctgtc tcatatgatt 11640 gtgcacatac ttgagactgt tttgaatttg ggggatggct aaaaccatca tagtacaggt 11700 aaggtgaggg aatagtaagt ggtgagaact actcagggaa tgaaggtgtc agaataataa 11760 gaggtgctac tgactttctc agcctctgaa tatgaacggt gagcattgtg gctgtcagca 11820 ggaagcaacg aagggaaatg tctttccttt tgctcttaag ttgtggagag tgcaacagta 11880 gcataggacc ctaccctctg ggccaagtca aagacattct gacatcttag tatttgcata 11940 ttcttatgta tgtgaaagtt acaaattgct tgaaagaaaa tatgcatcta ataaaaaaca 12000 ccttctaaaa taattcatta tattcttgct ctttcagtca agtgtacatt tagagaatag 12060 cacataaaac tgccagagca ttttataagc agctgttttc ttccttagtg tgtgtgcatg 12120 tgtgtgtgat gtatacaaag agagagataa ttgtattttt gtattttctt ttaaataatt 12180 tttaaaattg acccttttcc tgagacaaat tgccagaata gtttgtattt agagatggta 12240 cctctaagag taaggttgct ggttgctgag caattgactt gaaaactttt aaaattcaaa 12300 ttttaattcc actactcaaa agaattgcca tgttttaaaa aagagaattg gtgccataag 12360 ttagttgtct atgtttgaaa atgaagaaga tatgcaacgt catggcctgg tcacttaccc 12420 gcagccctga gttgtaggca catcatatgt gagaatgagg atgcttttct ttcatttaaa 12480 atccctcccc aaaacttggc tctaattgca gtcatgacaa tcatgtacat ttggatttat 12540 gtgcacgagt ctcttaccct gagagaggac aggtgctaca ggtggagggg acccgtctgg 12600 gtcacgttca cat 12613 <210> 26 <211> 61549 <212> DNA <213> Homo sapiens <400> 26 tctcgtactc ctgaccttga gtgatccacc tgcctcggcc tcccaaagtg ctgggattac 60 aggcatgagc caccgcgccg ggctaatatg ctcattttag tgaggcaaaa atagaggctc 120 agagtctgat ttgtacaaaa ctacagagca gttaagtgtc ctctcagatg tgtaccctga 180 tctgggtgac tctaggactc taggtctcaa ctgttacaac cagttaaggg tttggggaag 240 cactgggcca agagtcagga aaatggaagc cacaggtagt gcaaggtctt gggaatggga 300 cgtctggtcc aaggattcac gcgatgactg gaacccgaag agccggggcc cggtttacgg 360 ccgccatgaa gcaacgcgcg ccggtaggtt tgggaatcag ggagccctct gaataggaga 420 ctgagttggg agggaaaggg gcttcgctgg gggagcctcg gcttcttctg ggagaaaatt 480 cccacggcta cctagtgagc ctgcaaactg gtaggcgccg gcgtaggcgc gcgggcgggg 540 ccgggggcgg ggcctgcggg gcgtggcggg gcgggcagag ggcggggcct gcttctcctc 600 agcttcaggc ggctgcgacg agccctcagg cgaacctctc ggctttcccg cgcggcgccg 660 cctcttgctg cgcctccgcc tcctcctctg ctccgccacc ggcttcctcc tcctgagcag 720 tcagcccgcg cgccggccgg ctccgttatg gcgacccgca gccctggcgt cgtggtgagc 780 agctcggcct gccggccctg gccggttcag gcccacgcgg caggtggcgg ccgggccctg 840 aggcgcggga tccgcagtgc gggctcgggc ggccgggccc agggaacccc gcaggcgggg 900 gcggccagtt tcccgggttc ggctttacgt cacgcgaggg cggcagggag gacggaatgg 960 cggggtttgg ggtgggtccc tcctcggggg agccctggga aaagaggact gcgtgtggga 1020 agagaaggtg gaaatggcgt tttggttgac atgtgccgcc tgcgagcgtg ctgcggggag 1080 gggccgaggg cagattcggg aatgatggcg cggggtgggg gcgtgggggc tttctcggga 1140 gaggcccttc cctggaagtt tggggtgcga tggtgaggtt ctcggggcac ctctggaggg 1200 gcctcggcac ggaaagcgac cacctgggag ggcgtgtggg gaccaggttt tgcctttagt 1260 tttgcacaca ctgtagttca tctttatgga gatgctcatg gcctcattga agccccacta 1320 cagctctggt agcggtaacc atgcgtattt gacacacgaa ggaactaggg aaaaggcatt 1380 aggtcatttc aagccgaaat tcacatgtgc tagaatccag attccatgct gaccgatgcc 1440 ccaggatata gaaaatgaga atctggtcct taccttcaag aacattctta accgtaatca 1500 gcctctggta tcttagctcc accctcactg gttttttctt gtttgttgaa ccggccaagc 1560 tgctggcctc cctcctcaac cgttctgatc atgcttgcta aaatagtcaa aaccccggcc 1620 agttaaatat gctttagcct gctttattat gattattttt gttgttttgg caatgacctg 1680 gttacctgtt gtttctccca ctaaaacttt ttaagggcag gaatcaccgc cgtaactcta 1740 gcacttagca cagtacttgg cttgtaagag gtcctcgatg atggtttgtt gaatgaatac 1800 attaaataat taaccacttg aaccctaaga aagaagcgat tctatttcat attaggcatt 1860 gtaatgactt aaggtaaaga gcagtgctat taacggagtc taactgggaa tccagcttgt 1920 ttgggctatt tactagttgt gtggctgtgg gcaacttact tcacctctct gggcttaagt 1980 cattttatgt atatctgagg tgctggctac ctcttggagt tattgagagg attataagac 2040 agtctatgtg aatcagcaac ccttgcatgg cccctggcgg ggaacagtaa taatagccat 2100 catcatgttt acttacatag tcctaattag tcttcaaaac agccctgtag caatggtatg 2160 attattacca ttttacagat gaggaacctt tgaagcctca gagaggctaa cagacatacc 2220 ctaggtcata cagttattaa gagaaggagc tctgtctcga acctagctct ctctctctcg 2280 agtaatacca gttaaaaaat aggctacaaa taggtactca aaaaaatggt agtggctgtt 2340 gtttttattc agttgctgag gaaaaaatgt tgatttttca tctctaaaca tcaacttact 2400 taattctgcc aatttctttt ttttgagaca gggtctcact ctgtcaccta ggatggagtg 2460 cagtggcaca atcactgctc actgcagcct cgacttcccg ggctcgggtg attctcccca 2520 ggctcagggg attctcccac ttcagcctcc caagtagctg ggactacagg tgcgcaccac 2580 catccctggc taatatttgt actttatttt atttatttat ttatttattt tttgagatgg 2640 agtttcgctc ttgttgcccg ggctggagta cagtggcatg atctcggctc agtgcaacct 2700 ctgcctcccg ggttcaagcg attctcctac ctcatccccc tgagtagctg ggattacagg 2760 cgcctgccac catgcctggc taattttttg tatttttaat agagacgagg tttcaccatg 2820 ttggccaggc tactctcgaa ctcctgatct caggtgatcc acccgccttg gcctcccaaa 2880 gtgctgggat tacaggcgtg agccactgcg cccggcctaa tatttgtatt ttttgtagag 2940 atggtgtttt gccatgttgt ccaggctggt cttgaactcc tgagctcaag cgatctgccc 3000 gcctctgctt cccaaagtgc tgggattaca ggcatgagcc accgtgcctg gcctaggtag 3060 acgcttttag ctttggggtg tgatgcctgc cccagtatat agtgaattta attattgcta 3120 gagctggctg tttgttagtt ttctttgaac ataagatact cattgttttt agtttgcaaa 3180 tccctcttcc tttttaaaaa atttctttcc cttaaattgt ttgcatgtta gcaataacaa 3240 atgcttaaat ggtgctatgt gctagatact cttctaagcc ctgttatgta tattaactaa 3300 ttttttaaat tacacaaatc agagaggtta agtaacttgc ccaagattac ccaacaatac 3360 taggatttga acctaagttt gtctcacccc agattctgct cttaatctct aaacttttaa 3420 gttagtagtg acaatagtag gtatttattg aatacttaac tatgttttag gcgttgaagt 3480 aaatattttg caggcattat ctaatgtaaa caccctaaag ttacataaca ggtacccttt 3540 aggtaaataa acactagtat gaccttggag gcacagatag ttgaagtaac ttgcccaata 3600 tcacttacat gaaattggcc ctcaaatgtg tctgatacaa cccatgctgc ttgtaactat 3660 cgttttaaac tgccagggta aacttggaca cacttgagct aagaaaaagc ttttagattt 3720 ttgcaaatta atgtgaaaga tatgctttat gtggatataa tatcttctaa atttcgggga 3780 tggtagtcct agaaatgtaa tcctgcccta gccgagctta ccctgccaat aattttttac 3840 agaattggta aaacggagca cctttttttt gtccttggcc acactgttat caacagggtg 3900 tagattgaca tcaatctgta ggtgtaaacc agaattactc tttgtgacca ccaggaaata 3960 gagcagttca gttcaggggt ttctttctgt gaatttagca ctgtgacctg catactacaa 4020 gtctactttg ttttctatcc attgtttgta tctgggtatt gcaaaaggta ggaaaaggac 4080 caaccagatc agcagagaag agttgccttg gagttttctt ttagttttct gcagttcatt 4140 agatagtaac taggccatgt cattttactc ccttgtagtg aagatatgtt gaagttgtac 4200 tggtatactc ttctaccttt ctgtaatttt atattgtgta gacttgataa aatttatgtg 4260 tcaatcacca ccattaatat caatattgag cctcaattct tatttttctg cccagtggct 4320 gccaaattac taacatttac aataattcac tactactaag ataatctact agttcgatca 4380 catacttcaa attgttatgg aactactgtc ttcagcattg tgcttctgat aactgataag 4440 tataattttt tttttgtcca gagtgaacat gtctattctt ccactgtaca cactaataaa 4500 aggaaaaatt gtaatattgg gtaaattcat gtccttacac atgtagtagt tatgagccca 4560 tgtccctaga atgagtaata atttatccct cccttggttg aatagtcaag aatgctgatt 4620 ttaattcttc taacagcttt atccctcaga agggaaggca agcaagttat atatgtagtt 4680 tatttgtaag actgatatga aattggaaga tgaatctact attagcttta attattttta 4740 catttaggaa tattgcatca gtaactcata attttggttt tctgttatcc tgagttaaca 4800 caaattatcc aaggagatgg cggatcatct gctttgaggt gttttttttt gagaatttta 4860 atgtatctga atataaaagg taaaaatatg ccaactagca atttctgccc attccagaag 4920 tttggaaata ttactcatta ctaggaatta aataaaatat ggtttatcta ttgttatacc 4980 tcttttaatt cacatagctc atttttatct tttatttttg tttgtttttt ttgagatgga 5040 gtcttgctct gtcaccaggc aggagtgcag tgatgcaatc tcggctcact ctagccaccg 5100 actccctggt tcaagcgatt ctcctgcctg agccttctga gtagctggga ttacaggcag 5160 gcaccaccac gcccagctaa tttttgtaga gacaggattt caccgtgttg gccaggatgg 5220 tctccatctc ctgacctcat gatctgcctg cttcggcctc ccaaagtgct gggattacag 5280 gtgggagcca ctacgcctgg cccacatagc tcatttttag actcacttcc attaagtctt 5340 gtttggaccc acgaacattg tctttttttt tttaagatgg agtttcactt ttgttgccca 5400 gactgtagtg caatggtgca atctcagctc actgcaatct ctgcctcctg ggttctagca 5460 attctcctgc ctcagcctcc cgagtagctg gaattacagg cgcccgccac cacgcccagc 5520 taatttttgt gtttttagta gagacggggt ttcaccatgt tgggcaggcc aggggtgatc 5580 cgcccacctc agcctcccaa agtgctggga ttacaggtgt gagccaccgc atctggccaa 5640 catgtctttt tttttttttt cctttttaac cacaaagaga cttaagcagt ccttgtcaca 5700 gatgatgaat tgatgttgca agtattgtct tagcttggat taattttctt gcttactgta 5760 attttagata atatagcttt gtaattagag attttatgtg taaaccacaa aaatgtttac 5820 atgaaggcca ttattacaga tgtgacgtgc ataattatta gtaatttgta tgtttacatg 5880 ggtcagtctg gcaaaaaatt atgaagtttt aaaaattaaa aaaaattata atgccagttt 5940 tactggaaag taaaattatt tcagtaatcg attatagcaa aagtattgat tttcattcca 6000 gacaaaagtc agaatgaaag gtaatttctc aatactcttt cagattaata aaagtacctg 6060 tagcgatttt tatcattcac aagtatatca caagtaagtt agaatttgag aactgtgttc 6120 tagatctctg aggagatgca gtcagatttc tgaactgtct cagcaaatgg taagtaactt 6180 agagctagta attaataacc tgtcctttga tttctgattc agccaagaat ggccatattt 6240 gggaaaggca gatctggaga gtaaccacgt tttcattcat ttaccacttc taggcccctc 6300 cagagctctc agatattttg gggttgagcc cttccccaaa gccatacagg accttttttt 6360 tgtgatctgt tctagccatt tttatgttgg gtgcttgtta tggactgagc atttatgtcc 6420 tcccacaccc cccccatacc ttttttgaag tcctaacccc cagtgtgatg gtatttggag 6480 acagggcctt tggaaggtaa ttacagttag aagaagtcgg gagggttggg cccaggtctg 6540 attggattag tgcccttata tgaaaagaca ccaggacggg cgcagtggct cacacctgta 6600 atcccagcac tttgggaggc caaggtgggt ggatcacgag gtcaggagtt tgagaccagc 6660 ctggccaatg tagtgaaaca ccatctctac taaaaataca aaaattagct gggtgtggta 6720 gcgggctcct gtcatccaag ctactcggga gggtgaggca tgagaatcac ttgaacccgg 6780 gagttggagg ttgcagtgag cccagattgt gccactgtac tccagcctgg gtgacagagt 6840 gagactctgt ctcaaaaaag aaaaaaaaaa aaaaagagac accagagagc ttgttagaag 6900 aggtcatgtg agcacacagt tagaagacct tcaagccaaa gaagaggcct gagattgaaa 6960 cctaccttgc aggtacctta attttggact tcccagcctc caaaactgtg agaaataagt 7020 ttctgttaag tcactcagtc tgtggtattt tgttatggca gcctgagcag gtagttgttc 7080 tttcagaagg tgttgataat aaccacatgc aacaccaagt cacaaataat aaaacagatg 7140 taacttatat tcatacagaa agttgggcac tgccattgcc ttgttggttt acacggctgt 7200 gctagttcag tagcagaaag gtgctggtct cctttactca gtttacaatc taggcagtag 7260 aatgtaatca ctgctttaaa cttgatactg cttagggaga gaatcattgg tgctgggtaa 7320 ctttgggttc taggtttact ttttgtgtat atataactgt ttttggtaaa tcacaagttt 7380 ctgggcttgt cgaattagat tttgttacag attatgagct ttattatgct atacagttag 7440 ttgtatgtat atatgccttt cccactagat tttaagcttt tttttttttt ttttttttgt 7500 gacggagtct tgctcttgtc gcccaggctg aagtggagtg cagtggcaca atctcggctc 7560 actgcagcct ccacctccta ggttcaagcg attctcctgc ctcggcctcc caagtaactg 7620 ggactacagg cacgtgccac cacacccggc taatttttgt attttttgta gagacagggt 7680 ttcgccatgt tggctaggct ggtcttgaac ttctggcctc aggtgatcca cccgcctcag 7740 cctcccaaag tgctgggatt tacaggcatg agccaccacg cccagctata agctctttaa 7800 gggttgtaaa tttataatca ttcttttact ctcctgcaaa ttctgttgca cactgcctta 7860 atcaaggtag atgctgaatg catttttgta taattgaata tgttgcaatc cccaactctc 7920 tccaactgtt cctgtcaaag cagccactgg attgttaact aatccatatt agatggggtt 7980 aattaatatc agatgggaca agtaagggct aataagatta taggccacca agtagatttc 8040 tgtctagctc ttatagagat tgagtttatt ggacctgttt gataggaagt tttggtgttt 8100 gggatgatta aaactgaagt tcctatttat tgaattatac ctatttatat tatttcatat 8160 cagtggtcca catgcaagtg aggcttctga gacagagttt gagttctctc ttcaactacc 8220 ataacactta acctgtatct tttttttttt tttttttttt agacggagtc tcgctctgtc 8280 actcaggctg gagtgtagtg gtatgatctc ggctcactgt aacctctgcc tcctggattc 8340 aagcagttct ccatgtctca gcctccctag tagctgggat tacaggcctg tgccaccatg 8400 cctggctaat tttttttttg tatttttagt agagacgggg ttttaccacg ttggccaggc 8460 tggtctcgaa ctcttgacct cgagcgatca acttgccttg gcctcccaaa gtgctgggat 8520 tacaggcatg agccacagcg cccagccgtc ttttttttta aatagcaatt taacactgtt 8580 cacagttact catgtacatg tcatgccatc tattacactg taagttctgt gagggtagct 8640 gtatcaaatt tatctaactc tctctagtat gcatgacata gtaagtattc aataaatatt 8700 tgcatattag tgataaggat acaggttctg aatagtgggt ccttaccatt taagaattag 8760 tatttgatgg ccgggcgggg tggctcacgc ctgtaatccc agcactttgg gaggctgagg 8820 cgggcggatc atgagatcag gagatcgaga ccatcctggc taacatggtg aaatcccgtc 8880 tttacaaaaa aaatacaaaa gaattaacca agtgtggtgg tgggtgcctg tagtcccagc 8940 tactgctttg tgaggctgag gcaggcagat cacctgaggt gggaaattca agaccagcct 9000 gaccaacatg gagaaacccc atctctacta aaaatacaaa attagccggg cgtggtggcg 9060 catgtctgta atcccagcta ctcgggaggc tgaggcagga gaatggcgtg aacccgggag 9120 gcggagcttg cagtgagcca ggatcgcgcc actgcactcc agcctgggcg acagagcgag 9180 actccgtctc aaaaaaaaaa aaaaaaaaaa aattagtatt tgatatttga tcattaaata 9240 tgaattaaga ggacttagac tttttgttaa atgtcaagct gggaaaagtt gtcatttaaa 9300 tgaattgcct cttatttaat ttcgtctgat gatacatttt gtttttattt tgtaaaaaat 9360 tatttttttt ctttttggag acagggtctt gctctgttgc ccaggctggt cacaaactcc 9420 tgacctcaag caatcctcct gccttagcct cccaaaatgc tgggattaca ggcgtgagcc 9480 acctcgcccg gccttgtatt atgatacatt ttgaacaact acaagtagac ttggtataat 9540 gaacctgcac gtacccattg ccaagttctg acaactgtct gtctatagcc aattatgcat 9600 ttcttaaatt agaacccccc caatataccc aaatatatat atatgtgtgc atatatatag 9660 taagttgtaa caaagttgtg aattcatacc tgaagtatct caagtgatgc aagttttatg 9720 aatttttgtt tatgcctttt gggaagagtt gtattgacaa attttttatg cttaaagtaa 9780 accataaatc aaaaaaataa aatctaggat gcaataaaac aaaacaactt cttgacataa 9840 gtatggtatg taaatctgtt ttgattggaa atcaatttgt tatattgcca gaattcctgt 9900 tttagaatac atctctgctg atctgtctgt attcttagac tgcatatctg ggatgaactc 9960 tgggcagaat tcacatgggc ttcctttgaa ataaacaaga cttttcaaat tcttagtcga 10020 tctgcagaac ctgtagccag gcactgaacc attttgatag atgcagtaat cgttgcaagt 10080 gtatatttca aggagttctg gctgggtcct agtttatgct tgtggcagaa gcagtgagta 10140 actgggagga agttggtgag taagcttcaa ggaagaagtc atttttagta ctctggatct 10200 tcctgatttt aaagcactac aaaatggtgc attttcattc ttgtcaagtg ataacagata 10260 tattctgatg agcctgaaat gaatatatat tgtatcattt ttataatatc tagcaaggtt 10320 tgtattttcc tagaacttga actaaatttc agttcataaa atttataaaa tacttagttg 10380 ttgtaaaata tttttggaat gttcacatag gtgacacaca aatgtcccat tttcattctt 10440 tctatagtaa atatgttctg atatgtgaag gtttagcaga tgcatcagca tttaatccta 10500 gaggatctgg cataatcttt tcccccaaga atagaaattt tttctgctta tgaaagtagt 10560 acatgtttct ttaaaaacaa atcaatattg acttctgcct gctgtatagc actatgcctc 10620 cacctggcca tgaccagggg catgtcctgg tccacctacc tgaaaatgtt tgcaaccagc 10680 ctcctggcca tgtgcacagg ggctgaagtt gtcccacagg tattacgggc caacctgaca 10740 atacatgaag ttccaccaaa gtctgagaac tcagaactga gctttgggga ctgaaagaca 10800 gcacaaacct caaatttctc agcactggaa acctcaaaat ataactgaat tccataaata 10860 agattttaag tcttaaatat gtatttttaa atgtattaaa agtcaagctg cttgtattta 10920 agcacctaat acaatgctta ggttgtaaaa ggagatgctc aataggtact aactgatata 10980 ttgagattta attatggttt gaccaatatt tattggaaac cgccaaagct taaatcatca 11040 gcttcttgaa tgtgatttga aaggtaattt agtattgaat agcatgtgag ctagagtatt 11100 tcattctttc tggtttattt cttcaaatag actttgaata taatggtgaa tgggtattat 11160 aaattaacta ataaaaatga cattgaaaat gaaaaaatat atatattaaa gtgtagaaag 11220 tgaccaggcg tggtggctca cacctgtaat ccaagcacct tgggaggctg aggcaggagg 11280 atctcttgat cccaggagtt caagaccagc ctgggcaaca tagcgagact tcgtctctaa 11340 aaaaaaaaaa gagagagaaa aaaatttttt ttatttaaaa aaagtgtaga aagtgtcaag 11400 accccacttc ttaccattat ttggtatatt tctctatacc cacccaccct tcctccttac 11460 tccctccctc ccttcccaat ctttttatct ttttgtattc tgattttttg tttgtatatt 11520 ttgctttaat ttaatgtatc ctttaaaaat ttcccataca ttttatatgt atatataaaa 11580 acgcatgctg ccaaagataa tttataagaa agaccattga atttttttaa aagtgatata 11640 tattcattga aaaaaattta gaatatatag caaagcaata aagaactaaa taaaattgct 11700 gtaactcctc tttcaaagat aagtgctttt atgattttgt tgtatttttt tctgtatata 11760 ggtacatata tagtatttat aaagctgtac tcatagtaca ttttcacatc acaggtacca 11820 tatcagtgtt attaaatatt ttgtatgcca ggggctagac ataccaagac aaccaatatg 11880 tggttctact taaataatat tagagtatct tttatgatga cacttcatga gttgactata 11940 ataatcttag acttctaaga gtttgggttt tcaaaagatc acttagcttt tttgggtgat 12000 ttttccccct tactgtgaga tgagagaggc tgtttggatt tgggattggg gtagcgggga 12060 cagcaacttt tcttttcttt ttctttttta ttttgaggta gggtattgct gtgtcaccca 12120 ggctggagtg cagtggtgtg atctcggctc actgcaacct ccacctcccg ggctcaggtg 12180 atcctcctgc ttcagcctcc ccagtaactg ggactacagg cgcgtgccac atgcctggct 12240 aattttgtat ttttagtaga gatggggttt caccatgttg gccaggctgg tctctaactc 12300 ctgacctcag gtgatacgcc cacctgggcc tcccaaaata ctgggattac aggcatgagc 12360 cgctgcatca gccagcagtt tttcttgtgg ttttttttgt ttgttttgtt ttgttttgtt 12420 tttgagatag ggtcttactc tgttgtccac gctggagtgc tgtggtatga tcgtagctca 12480 ctgcagcctc aaactcctgg gctcaagtga ttccttctgc ctccgcctcc cgagtagctg 12540 ggactacagg tatgcaccac catacctggc aaatttttac aaagtttttt gtagggacgg 12600 ggtcttgcta cattccccat gtcggtcttg aactcctggc ctcaagcaac tctcctgtct 12660 cagcctccca aagcactggg attacaagtg tgagccacca caccatgcca gtttttcctg 12720 ttcagtgtga tattttatct tgttagacta cagtgtgtta aaacttgttt tactaaattt 12780 tcaaacatac tcaaaagtgg agagaatagt ataatgaata cccgtatgtt catcacccat 12840 gtttagaata ttattaaata taaagatttt gctgcgtttg tcttagctct ttaaaatttt 12900 tctttttctc tttgtgacct aaaggaaatt ccatatctta tcactttact tctacattct 12960 tgactaagat gactaagaca tatagttaca tggttttttg ttttgttttt tgttttttaa 13020 agacgaaatc tcgctcttgt cccccaggct ggagtgcaat ggtgccatct cagctcagtg 13080 caacctctgc cttctgggta caagcgattc tcctgcctca gcctcccaag tagctgggat 13140 tacaggctcc tgccaccacg cctggctaat ttttgtattt ttagtagaga cggcgggggg 13200 aggtttcacc atgttgacaa ggctggtctg gaactcctga cctcaggtga tccacccgcc 13260 tcggcctccc aaagtgctgg gattacaggc gtgagccacc gcgcccagcc tgtttttttg 13320 tttgtttgtt ttgttttttt tgagacagag tcttgctctg tttcccaggc tggagtgaag 13380 tggcgcattc ttggctcact gcaaccttca cctcccaggt tcaagtgatt ctcctgcctc 13440 agcctcccaa gtagctggga ctacaggcat gtgtcaccac acccggctaa tttttttgta 13500 tttttagtag agacgggatt tcaccgtgtt gcccaggctg gtctcgaact cctgagctca 13560 ggcagtctgc ctgcctcagc ctcccaaagt gctgggatta cacgtgtgaa ccaacccgcc 13620 cggcctgttg ttttcttaca taattcatta tcatacctac aaagttaaca gttactaata 13680 tcatcttaca cctaaatttc tctgatagac taaggttatt ttttaacatc ttaatccaat 13740 caaatgtttg tatcctgtaa tgctctcatt gaaacagcta tatttctttt tcagattagt 13800 gatgatgaac caggttatga ccttgattta ttttgcatac ctaatcatta tgctgaggat 13860 ttggaaaggg tgtttattcc tcatggacta attatggaca ggtaagtaag atcttaaaat 13920 gaggtttttt actttttctt gtgttaattt caaacatcag cagctgttct gagtacttgc 13980 tatttgaaca taaactaggc caacttatta aataactgat gctttctaaa atcttcttta 14040 ttaaaaataa aagaggaggg ccttactaat tacttagtat cagttgtggt atagtgggac 14100 tctgtaggga ccagaacaaa gtaaacattg aagggagatg gaagaaggaa ctctagccag 14160 agtcttgcat ttctcagtcc taaacagggt aatggactgg ggctgaatca catgaaggca 14220 aggtcagatt tttattatta tgcacatcta gcttgaaaat tttctgttaa gtcaattaca 14280 gtgaaaaacc ttacctggta ttgaatgctt gcattgtatg tctggctatt ctgtgttttt 14340 attttaaaat tataatatca aaatatttgt gttataaaat attctaacta tggaggccat 14400 aaacaagaag actaaagttc tctcctttca gccttctgta cacatttctt ctcaagcact 14460 ggctatgcat gtatactata tgcaaaagta catatataca tttatatttt aacgtatgag 14520 tatagtttta aatgttattg gacactttta atattagtgt gtctagagct atctaatata 14580 ttttaaaggt tgcatagcat tctgtcttat ggagatacca taactgattt aaccagtcca 14640 ctattgatag acactatttt gttcttaccg actgtactag aagaaacatt cttttacatg 14700 tttggtactt gttcagcttt attcaagtgg aatttctggg tcaaggggaa agagtttatt 14760 gaatattttg gtattgccaa attttcctct aagaagttga atcattttat actcctgatg 14820 ttatatgaga gtacctttct cttcacaatt tgtctctttt tttttttttt ttgagacaag 14880 gtctctgttg cccaggctgg ggtgcagtgc agcagaatga tcacagttca ctgcagtctc 14940 aacctcctgg gttcaagcga tccttccacc tcagcctcct gagtagctgg gactataggt 15000 gtgcgccacc actcccagct aatattttta ttttgtagaa acagggttcg ccatgttacc 15060 cagcctccca aagtgctggg attacaggca tgagccactg gcccagtttc tacagtctct 15120 cttaatattg tatattatcc aagaaatttc atttaatcag aacctgccag tctgataggt 15180 gaaaatggta tcttgttttt atttgcattt aaaaaaaatt atgatagtgg tatgcttggt 15240 ttttttgaag gtatcaaatt ttttacctta tgaaacatga gggcaaagga tgtgttacgt 15300 ggaagattta aaaaaaattt ttaatgcatt tttttgagac aaggtcttgc tctattgtcc 15360 aggctggagt gcagtggcac aatcacagtt cactccagcc tcaacatcct gcactaaagt 15420 gattttccca cctcacctct caagtagctg ggactacagg tacatgctac catgcctggc 15480 taattttttt ttttttgcag gcatggggtc tcactatatt gcccaggttg gtgtggaagt 15540 ttaatgacta agaggtgttt gttataaagt ttaatgtatg aaactttcta ttaaattcct 15600 gattttattt ctgtaggact gaacgtcttg ctcgagatgt gatgaaggag atgggaggcc 15660 atcacattgt agccctctgt gtgctcaagg ggggctataa attctttgct gacctgctgg 15720 attacatcaa agcactgaat agaaatagtg atagatccat tcctatgact gtagatttta 15780 tcagactgaa gagctattgt gtgagtatat ttaatatatg attcttttta gtggcaacag 15840 taggttttct tatattttct ttgaatctct gcaaaccata cttgctttca tttcacttgg 15900 ttacagtgag atttttctaa catattcact agtactttac atcaaagcca atactgtttt 15960 tttaaaacta gtcaccttgg aggatatata cttattttac aggtgtgtgt ggttttttaa 16020 ataaactcct tttaggaatt gctgttggga cttgggatac ttttttcact atacatactg 16080 gtgacagata ccctctcttg agctacatcg gtttgtgggg agtcaaaagt cctttggagc 16140 taggtttgac aaataaggtg ggttaacact tgtttcctag aaagcacatg gagagctaga 16200 gtattggcga attgaagaaa tccccctttt tttttaacac acttaagaaa ggggactgca 16260 ggtatactca agagagtaag tcgcaccaga aaccactttt gatccacagt ctgcctgtgt 16320 cacacaattg aaatgcatca caacattgac actgtggatg aaacaaaatc agtgtgaatt 16380 ttagtagtga atttcattca taatttgatc gtgcaaacgt ttgattttta ttactttaga 16440 ctattgtttc tgattttatg ttgggttggt atttcctgtg agttactgtt ttcctttaaa 16500 ataggaattt ttcatactct tcaaagatta gaacaaatgt ccagtttttg ctgtttcatg 16560 aatgagtcct gtccatcttt gtagaaactc gccttatgtt cacattttta ttgagaataa 16620 gaccacttat ctacatttaa ctatcaacct catcctctcc attaatcatc tattttagtg 16680 acccaagttt ttgacctttt ccatgtttac atcaatcctg taggtgattg ggcagccatt 16740 taagtattat tatagacatt ttcactatcc cattaaaacc ctttatgccc atacatcata 16800 acactacttc ctacccataa gctcctttta acttgttaaa gtcttgcttg aattaaagac 16860 ttgtttaaac acaaaattta gacttttact caacaaaagt gattgattga ttgattgatt 16920 gattgatggt ttacagtagg acttcattct agtcattata gctgctggca gtataactgg 16980 ccagccttta atacattgct gcttagagtc aaagcatgta cttagagttg gtatgattta 17040 tctttttggt cttctatagc ctccttcccc atccccatca gtcttaatca gtcttgttac 17100 gttatgacta atctttgggg atttgtgcag aatgttattt tagataagca aaaacgagca 17160 aaatagggga gtttaacttt aatattttct tttaaaaagc atttcatgtt ataagatcaa 17220 ttctgagtgg tagaaatgct ttgacatttt atttccattt tctactttta gtttttttcc 17280 tatttgttta agatcttaga ggattattaa gctgaactcc tcaactgata aaaagcatga 17340 catcttaaac ataagcaaag catattttta ggttaatttt cacatagaaa acagtttatt 17400 ttatgtgaaa ttctatgtag atatactatt tttttggtat ttattgatat gtttatttta 17460 ttttatttta ttttatttta ttttatttta ttttatttat ttattttttt ttttgagaca 17520 gagtctcact ctgttgccca ggctggagtg cagtggcatg atcgtagctc actgcaacct 17580 ccacctcccg ggttcaagca attcttctgt ctcagcctcc cgagtagctg ggactacagg 17640 tgcctgccac tatgcccggc taatttttgt gtttttagta gagatggggt ttcaccttgt 17700 tggtcaggct ggtctcgaac ccctgacctc aggtgatcca cccacctcag cctcccaaag 17760 tgctgggatt ataggcatga gccaccgtgc ccggccgaca tgttaatttt ttaaaaaagg 17820 ctttactggg gtatatttta tataatataa taatcacatg ttttaactat acaattccaa 17880 gctttttagt atatttatag ggctatgcaa ggaagatata ctgttaaaca gtagaaattg 17940 agaaagctct tctgataata tctcttgatt tgatgatggc tcatgcctgt aatctcagtg 18000 ctttggaagg ccaagacagc agaatcactt gaggccaggg gttcgagacc agcctgggca 18060 acacagcaat accctatctt tacaaataat aaaaatatct gttgatttga agtaaagttt 18120 ttttttaaag acaaggtctc attctgtcac ccaggctgga atgcagtagc aagatcacag 18180 ctcactgtgg ccttgacctt ctgggctcaa gtgattctcc cacttcggcc tcccgagtag 18240 ctgggactaa caggtgtgca ccaccatggc tggctaattt ttttttatgt ttgtagagat 18300 tgggtcttac tgtgttgccc aggctgatcc cgaactcctg ggctcaagca gtcttcctgc 18360 ctcagcctct aaaattgctg ggattacagg cttgagtcac catgcccagc ctgaagtagc 18420 atttctaccc tgtttaataa ttcagcagct tgtcatgtaa gatattcata tatgcatata 18480 aaacattagg cagcttaatt tggtaaaact gtaaaatgga aattttaaat tgtttgcagc 18540 atcaataaca ttgatgtcag tatgattttt acatgctgat cttgaccaat ttgaaacagt 18600 gagttaaaat ctggctgatc cgtactaatc ctaaagaaat attctatgaa ctattaaatg 18660 tttccagaat atataaagaa acattatgat gtcaacacac ccatctattt ttttttggaa 18720 ataaaaactc catttttctt attaaagaaa acatgcttat tagaaaacat acggctgggt 18780 gcagtggcac acatgtaatt ccagtgcttt gggagatcga ggtgggagaa tcacttgagg 18840 ccaggagttt gagaccagcc tagacaacat aatgagaccc cctctctaca caaaaagaat 18900 tagttgtgca tggtggcgtg cacctgtagt cccagctact tgggaggcag aggcaggagc 18960 atcccttgag cctaggagtt tgagactgca ggagttcgag actgagtgga atgcagtgga 19020 actgcattcc agcctgagtg acagagggag accctgtctt aaaaaaataa gaaagaaaac 19080 acaactgcag aaaattataa aggatttaag tcattccaaa tatcactgcc actttttatt 19140 tagaatattc taaagaattc tctctctgtg tacacacaca catatgcgta ctcttaatcc 19200 aagtagcttg gtaggatttt atttacctag tgcctagatg ggaaattgcc tggggattcc 19260 aaatacctat ttcattaaat taaagatgtc actgatttta agacttaaca ctatttttca 19320 tactgccaag aaagaaaaca ctaccagtta taaatgtaaa ttgccatcaa ttgtaataca 19380 tcaattttag agctattatt aataaaatgt gaatgtgcat cttagagcaa tgaaatatag 19440 tactatatat ttgatgacct tttctgccct gtgatattca gaaagtgaaa gttaaatatg 19500 ggctgagcat ggtggctcac acctgtaatc ccagtacttt gggaagtcaa gacgggaggc 19560 tggcttgaac ccaggagttc aagaccagcc taggcaatgt agcgagacgc catctcaaaa 19620 tattaaaaat aagtaaataa gtaaataaaa agaaggttaa gtatacaaat gtatttcctt 19680 tgttgtgaat ttatttcaat tttatagtga tttttttttt ttgagacgaa gtctcactct 19740 tgtcccccag gctggagtgc gatggcgtga tctcagctca ctgcaacctc tgcctcccag 19800 gttcaagcta tactcctgcc ttggcccccc gagtagctgg gattacaggc gcctgctacc 19860 atgcctggct aatttttgta tttttagttg agatggggtt tcaccatgtt ggccaggctg 19920 gtctagaact cttgacctct ggtgatccac ccgcctcgga ctcccaaaat gctgggatta 19980 caggcgtgag ccaccgtgcc tggccagtgg ttttttgttg ttgttgttgt tgttgttttg 20040 tttttgtttt tgtttttgtt ttgagacagg atcttgctct gtcacccagg ctggagtgca 20100 gtggtgccat cttggttcac tgcaacctct gcgtgggctc aagcaatcct cccacctccc 20160 tttccagagt agcggggacc acaggtgtgt gccaccacac ctgactaatt tttgcatttt 20220 tttttgtaga aacagggttt tgccatgttg cccaggttgg tctgaaactc ctgagctcaa 20280 acaatccaac tgccttggct tccctaagtg aaattacagg catgggccac tgtacccagt 20340 ctagtgattt ttttattttt atttttattt tattttattt tattttttta ccaaaaaaac 20400 aacaaagcct caggaggaaa agttgataca caagtaaatt ttattggaaa tgtttttgtg 20460 tggaccttaa gcagagggaa aattagtctg cattatggtg tatccagact aaatgactga 20520 tattaaaatg aaattattct taggatttgc aatcttagag aaaacttttt catttttatt 20580 tttttgagtt acaaattatc ttcatttaca tttgagaaca gtgagtcaca gagggattaa 20640 gtaacttact caagatcata caagtctttg atttgaaccc aatcttttaa ctctgcagaa 20700 ctcagagtca ctcttatttg gaaaaacttt ttaactgatg tggatcctct aatatgggct 20760 tcctattatt cattctctat tagtcagaag ttttgcaagc agacagaatt cattttgcca 20820 attacgggat tttccctcag ttgcagtcaa ggttcataaa actataactc tttatcttta 20880 attagaaatg tttttttttt tgagacaagg tcttgctctg ttgcccagac tggaatgcag 20940 tggcatagtg gcccattgca gctttgaact cctgggctca agggatcctc tgcctcagcc 21000 tcccaagtat ctgagactac aagtgcgtgc catcacccat ggctatttta aaaaaaaaaa 21060 aaattgtaga gatagggtct tgctgtgttg cccaggctgg tctcaaactc ctggtctcaa 21120 gcaatccttc tgccttggtc tcccaaagtg ctgagattac aggtgtcagc cgttgcacct 21180 ggccaaaacg ataacttaaa atacacacac acacacacac acacaaacac atatgtgtat 21240 ttgtgtgtgt gtgtgtgtgt gtgtgtctca aaaggtatca aaagagaata gctataactt 21300 tagtgttgat cttgatagtg acttgattag gctctgttta acatcaaaga tgcaaattaa 21360 tactttcttt gaacatatta aaaatgcaga aaatattgga gtattttatt ttaaataaat 21420 tgtattctgt atatttaagg tatacaacat gatgttatgg gatacatata ggtggttaaa 21480 agattactgc agtgaagcaa attaacgtat ccctcaactc acatagttac ccattttttt 21540 tttgttttgg tggcaagagg agcttaaaat ctcatttagt gtgaatccca aatacagcac 21600 aattttatta cctatatact tcatgttgta cattatattt ctagacttgt tcatcctaca 21660 tatctgctac tttgtatcct ctgagctaca tctccccatt ttctcacttg ccccccaagt 21720 agtttcttaa agtgtctcat gtaagagggc agtagctttc agcttaaact ttttctctgt 21780 atgtagtcga tttctttgag gtatactttt ctctccagaa tagttagatg taggtatacc 21840 actttgatgt tgacactagt ttacctagaa cttatcttct gtaaatctgt ctctatttcc 21900 atctctgtct ccatctttgt ctctatctct atctgtctat ctctatctat ctatctatct 21960 atctatctat ctatctatct atctatctat ctatctaaag caaattcatg cccttctcct 22020 atttattgaa tcgagaccat agacaggggt gagagaaaga atttggcagg aatggggatg 22080 tgtattatct gtggcataag gaaactttac agaactaggt tcaaaagtat actttctagt 22140 tctttcccat ggcttttcac tttgatgtag tccttatcag gtaactgagg ttttatataa 22200 gtcccctgat tcttagaaca tgaaggtgta gtagtcaagg ttggtccctt gaaaccacaa 22260 attttgtgaa aaaaaattaa gaaaattgaa taatttcctc agcaaataca tattgatcat 22320 ctgttataca gccatgagaa gtggttctgt tgcacacgtt tattttatca gatcctaatc 22380 ccaaaccagg cataaaatgg aaaccatgaa gataggatga aataacttct gaatgtttga 22440 atgtttgaaa atagtgtact taaaaatacc aggtggtttt tgtttgtttt ttgttttttt 22500 ctttttttga gacagggtct cactctgtca cccaggctgg agtgtagtgg tgcaatctca 22560 tctcattgca gtcttgacct cccaggctca ggttatctcc cacctcagcc tcccaagtag 22620 ctgggactac aggcacatgc caccacgccc agctaatttt ttgtattttt tgtagagacg 22680 gggtttcacc ctgttgccca ggctggtcta gaactcctgg gcttaagcga tcctcccacc 22740 tcagcctccc aaagtgctag gattacaggc atgagccacc atgcctggca gaaaatacca 22800 ggtttttaag tatcagcact tactcttcaa tcttttctat tactatgttg tgctaaatgg 22860 tattttttat ttaattagag caatgctgtt caatagaact ttctttgagg atggaaatct 22920 tttatgtttc tgctatgtgg tacagagcca ctagtgacat gtggcttttg agcgcttgac 22980 acatcttgtg caacacagga actgaatttt taagtaattt atattgccac atgtggctac 23040 cgtatgggac agtgtagtac tagatgatct gtaagggctg tgcttcatca gtgtcgtttt 23100 ttaactgaca aaaaccttta gttttttttt tagtaatgtg tttatttaaa agaattcata 23160 aaatacaagt aaacaaatta acttgttacc tgagcatatg tcctttcata cttatttttt 23220 ctgcatacat attttggaaa atggaatatc tgcccttttt ttttatctga gatacagtct 23280 acctctaaaa atacatgatt ctaacattct cacttttgtt ggcatttgat cagggtatag 23340 aaaaacagtt aaaaggacag agaatggttg agagattatg atatgaagag aaaatgtgat 23400 tgagtgtggt agacttgggg cctgcttgaa tgttgagaga atgactgttt tccgataaaa 23460 aaaaaaagtc cattctagga tcctaaaaga agggtctgaa gttcactgca gaaagcaagc 23520 tacatagtac taagccacta aggggacatg gagcccttag taattcctac cttagtaata 23580 gtctcatcat gccctcttgg gaacccagcc ttgttgatta gcctctctgc tttctctcct 23640 tatagttcaa cctccctgtt tgttccaagc agttcttttc ctgcccattt attatgcatt 23700 tctatacagc tttcctcctc tttttctata ccatgctgca gttcttattg ctacctagag 23760 gttttcaaaa ttcctagggg cggataagta ggcataaaca aagttcttcc ctattatcct 23820 tcctattttt tcacctagac tgaagaggta gacaaaatag aaataaagac attaagggta 23880 tgtgtttgta gtcccaaaga gcttctctgg caattttatg tagttgacag tgacgctctg 23940 agttcaggac agattggact ccttggctga gaggagtgag gagataggac ggtagaggag 24000 agggtagagc aactctggag gaagctttcc cctcaccttt gccagtcctg ttatcctaga 24060 cttaaccata attaaagatg agggaggcac tcagtaaagg gatctagtgg gaagcttgtt 24120 ccagacagcc aaggagggag gttcgcgcag ttcctttggc cacccaggtg gggtaattga 24180 tccatgtatg ccattcatgt acaatgtagg cacttatacc tgtattccaa tgtagtgaac 24240 tataccatta ctcttaaatt aatattcttt attagcttcc atggtggcta taggccaggc 24300 aagagagtta agaaaaaata aatagccagg tatggtgact caagcctgta atctcggcac 24360 tttaggaggc cgaggcagga ggatcgcttg agtccaggag ttcaagacca gcctgagcaa 24420 aatagtgaga tcctgtctct attttttaaa aaagccttgg ggcaaacagg agtatggagg 24480 tttggatgct aatagaacag cagtgtctta ctgcttggag ttctcttgtt tcttgtccta 24540 tcaccgtagc ctttggatca cagcaatttt tccatgactc catacttttc agttcttgaa 24600 tattttttcc tttattcctc ttgtctctgt aaagacatca actggagttg gactgtaata 24660 ccaggtatct ccagaagatg gcactattta acagatttta taaataattt gatgtgagtc 24720 actgtcatct gaagcttgtt gccttttctt tctttcttct ttcttttttt tccccatcaa 24780 ttctgtatgt ttgaaatgct gggttttaag ttagttagaa taagggatgt ctgtaatttc 24840 cctaaattga gaagtaatat gcaaaggttg atatcagaag tcatatgctc accttgcaac 24900 accaaataat actggcccat ttgtgatttt tgaaagtaac actccataat aaatggatgt 24960 atatatagaa gcataacaaa aatagaagca cataaaagtg aaaagtctca taaacgccat 25020 tgtcactact catgtaattg ctgttacaaa tttgtttaaa tgttgaataa aaatggtgtc 25080 ataggcaaca cagtgttcca ctacttggtg tttttaatag cattattctg tctcagtgtg 25140 ctttggatta tcaggtgctt tttaatagtt gcatggtatt acattgtgta gatgaacttg 25200 attaatttaa atggttccct gttaatggac atgttggttt gtttttgtga acaactgata 25260 cagtgaacat ttatttttta aataaaaaaa agagagacag ggtcttgctg tgtttctcgg 25320 gctggccttg aactcctggg gtcaagcgat cgtcttgcct ctgcctccct gggattacag 25380 gcatgaagcc accgcacccg gcccagtgaa cactcttgaa tgtatctttg tatacttgtc 25440 agtgtttttg tagcattgat tcccagaagt gggattactg gattaagtga catgcatgtt 25500 tgcaatttta acaggtattg ctatgtcatt ttcaaaagaa gctatgccaa ttaatactct 25560 caccaacaag agtgcttatt tcccctcagc atattatcag gcttaagttt tgccagtatg 25620 ggtgggagaa cagtagaatc acattgtttt agtgtttgtt tctcagatag atataatttt 25680 acaccttata accttctctt ctataaattg tctatttgtg ttcattctcc attttcctat 25740 gggttcttat tgttggagcc caatatataa aagggggtat ttgttacaga acctcttcag 25800 ttttggttca tgtcatgcct gggtttttac cctttctacg gatgttaaaa aaaattctct 25860 attttcttcc agtccactta tggctttatt ttttacattt agattttaat ccgtctggaa 25920 tttatttttg tgtatgctgt gaggtaggga ccatactttt attttttccc aaatgggtta 25980 ctagttggcc aaacatcatt tattgaataa ttcatctttt ccctactgac tcgaaatacc 26040 atctttattg tatactaaat cctcatatag ttctgggtct gtttctgggc tctactttgt 26100 tcatttactg tgctggtact gcaccgttgt aattgctgtg gctttgtggt atggtatggc 26160 ttgctctctg ctagggcaag tcgaagctct tttgttcacc tgctctttca cccaaatttt 26220 ctgtcctgaa tccagcacag ccaaattatg gtcattgtca ccaccaacta cagtgggtgt 26280 tgagcatttc ccattgaatc tcctgtaagg gttttattgg attctgtgat agcagtaaaa 26340 tgggagccta agaggtattc cttaaaggac tactaatcag acctggtttc ccagatgatg 26400 ctgaagatga cggggcctgg gctagacttt tgagggacat atccttgggg ttgggtgtga 26460 tatagaccag cccttacaat ttgcttgact catgggaatc gtacagggcc agaaccagac 26520 acctgtcatg ctaataactt ccctcacaat tcagaaatca ctgtgattga agatgggtgg 26580 ctgttataat actacccact taaaaatgga tgtaacccat tttttaggac tcttaaaaac 26640 atcaaatcag taatggccga ttaggacttt ttaattttta ctaatctcta cttgaaagtt 26700 ttctagtcat tcatttcagg aaacctaatt cttataattc atatcattta gaatatcata 26760 atgctatgga tattagctag ctaacttctc aaatcttcta gttctcattt aatttgaagt 26820 ttgtgtgtgt acataaggat atacatatac atatgtgtgt gtagatatat atatatatag 26880 tttttttttt ttttaactag aatgaccagt caacagggga cataaaagta attggtggag 26940 atgatctctc aactttaact ggaaaggtat gtatcttgaa agggaagaaa aaaaagcact 27000 tcataccgag tcaattagta acagtgtgct ttcaatcaat cactaagaga taatttacat 27060 agtataacta aatgggttat ttaacccttg gaagcagtct aggttaatta tcgttcccta 27120 ggtcatgtag taaaaagaca gtagaatcca acattaacct taaatgtcca tattgtcaag 27180 tactgctgtc tgcctctgtg ggactctaat ttgggatcct tcaaaaaaca ttgatggggg 27240 aaaagatagc ctttaaaaaa aaaaaaaaaa caaacctatg tgagtctatg tgaggtagac 27300 tcacatagtt tcctaaaaga tagcaaagca gtattatgta gtggctgaaa gtgtgagttc 27360 cggagcctga caactgattc aaagcatggc ttagtacttc ctaactctga ccttgggcaa 27420 gttacttaac ctctctgtgt cccatatgtg attagggtga ggttgataat agcagccata 27480 gagttaagag gattaagtgc tataatgcaa gtagagctct tacaacagtt tctggtaaat 27540 cactcaataa attcagacat actattattt taagaaatct caaagagttt tcttgtacct 27600 taaaattctc ctagtgtgaa ccattggttt tggtatattg tgcttccatg tagtttaata 27660 tcaagatgtt tttagatttc ccttttaatt tatttgttga cccattggtt gttcaggagc 27720 atgctgttta cctgaaaata atggagatat taaggtattt gaatatttat cttctagtac 27780 attgaaaaac tttttgagag taaccaataa taaatgatgg aatgctactg cttttttttt 27840 ttgaagctgc cagttattgt ttacttacac tatgccaaat ataaaggcat taatctcata 27900 aaagtttcac aacaatcctg tgagggagac gatatcccca ttttacaaat caggaaatta 27960 agacttaata aggttaaaag acttgcccaa agtcacagaa ccagtaagtg gtagagcttg 28020 aatttgaata cagacctgac tctaaagctc ttttctttct ttagatttta gtgttcattg 28080 cttacttgaa tgagtatcta taagaaaact ttaacatgta aaacttctgt gaaattatct 28140 tgtcccatat cagggtcatg tcaaactaat gtcctcctca gcatctttgg aaaacttcag 28200 aggagaaatg agctttgccc ctcctgttca tttcatatac cactgttaga cctgtccttc 28260 cctttcagca tgctttgtcc atatttagaa gctgttgaag ccattacttg tctggtcagt 28320 ttttagtgct ggaatggacc tagcctttta ggccttctga gatttagttt gatctcgtct 28380 ttcccaccta atggctctgt tctactacat agatttgatc tgaaacagtt ctctgtttct 28440 aaaataactt tcttttcatg atagtcacag taaagtacat ttattatgga aaaatcaata 28500 agtataacga gtgaaagtta tttcttggtg gtaagattat gggattattt gaactttctg 28560 tttcattgta ttttatttat ttatttattt ttgtgatgga gtctcactct gctgcccagg 28620 ctggagtgca gtagtacgat cttggctcac tgcaacctcc ccttcccagt tcaagtgatt 28680 ctcctgcctc agactcccaa gtagctggga ttacaggcgc acgccaccat gcctggctaa 28740 tttttttatc tttagtagag acagggtttc accatgttga ccaggctgat ctccaactcc 28800 tgatctcagg tatccacctg cctcagcctc ccaaagtacc gggattacgg gtgtgagcca 28860 ccctgcctgg cctcattttg tcttttgggg gtatttttgt gtgcagatat atatgtatat 28920 aaatattttt ccctcttttc cccagttagt atttgagcag atgaactttg gacccgaata 28980 cctgtattca agtctctaat accacttctt ggctattttc attttatcaa atggcctctt 29040 atcctcgttt ttctcattta ttaagtagag atgtaactac ttgatataat tcaaaaactc 29100 aataatggca ttcttttgtt ttttagactc tagtgtctgt actcgttgta ccatgctggg 29160 attcatttga acaattgcat ggctttttta gtgtattatt aaatttgcag tttacttaga 29220 atttactggg acctcataca aatgggaaaa aaacataact gtgttactca tttgctgtgt 29280 gcctttggat tgaccctatt ttttgtattc attttctccc catgtcctga gttccacttt 29340 gaataaaaag taattttttt cctgcctgta aaataggcta ccaataggct gcagttgtct 29400 atagtagctg cttcactgag gagagctcag catgagagaa atagtatgaa ttgcttgcca 29460 caagttatgg gctagcctta cttcattctg tacttggacc tgtttaggct tctaagagat 29520 cttacctcca acaataaact gctttgagac atgaaaaggt ggaagcttta cttggttata 29580 actttacttt taatacctag aacagtgagt cttcaaactt gtatttgcat gcccaattta 29640 taaaaagttt cctgagcatt tacccctaat atatgcattt taaattatat atgatttatg 29700 gtaataataa tatatatgtt acaaaataca tacaaaaata tagattaaac aaggtgaggt 29760 aaaaaattta aaagttctaa tctttcttgc aaaccagtgg atcttttgtg ccttactctg 29820 gtaaacactg tcttagaaga atatatagaa cattaaaatc ttaatgctat agttatatga 29880 cagagtatga tgagagctac agataaacaa cacatcatga atcttcttgt ggcagtgttt 29940 ataaccatta tgtgaaatgc tgcctcattc ttataactag cataagaaca gataggactt 30000 tctcgatttt gaggggtaat tattagatgg tattttctgt taaggactct tccagctata 30060 aaattcttaa atgtagaaag cgaagtgagg gtttatggtg agaggaagca ttggtatcat 30120 gttttagtgt agtccaagaa tatggacaca tccagaaaat gcagatcaag tttagcctaa 30180 tgagaaaata tattttggag tccatatggt aaattaaatt atgtgatttt tgagttattg 30240 tacaaatata attcttagaa tgttagagtc aggagactat aagagaccaa ctgcttcaag 30300 tttcatttaa cacatgggaa actaaggcca gagaaatttc aagacttgcc caagattaga 30360 cctcttgtta agtaatgaaa gtgttttaaa aacaggtggg tcaaattctg tttttaaaat 30420 ttccattatg atgaaaattt cagtattaca ggcttccaaa tcccagcaga tgggccactt 30480 gtttaaagga gagtttgata taataaagca tctaaaaaca agagtttgga taattcctta 30540 gggttgttat gatgtgattt gacttataat tggaaatacc gttttattca ttgtactgat 30600 tttcatttct ctttttcttc tagaatgtct tgattgtgga agtaagttca catttacttt 30660 taatataaca tttatgactt ttctaactta gtatgcacca tcctaaaggt aagccaggga 30720 gagaaattcc tctgcatcag ttttaatggt gggcttgtgt tctaaaggag tgagattggt 30780 tttttgtaaa gactacttag taatttgttt ttaccaataa tggaatggta tacttcctac 30840 ctctcttttt ttagtttgaa gtattttctt tctaaacata actctctctc tctatttatc 30900 tatatataat atatacatat atatcttata ttttatgtat atatatatat atcttgctta 30960 gattttgtct tatgtaatat ttggtacata aaaaataata tttataattt atagactatt 31020 ttccatgtgt tattatgtgc taaagtattt tgtatcttag caccgagagg ctaagcagtt 31080 tcctagggtt accagctagt aaactaaggg aaacctttac ttcctttagc tcagtggttc 31140 tcaaaatgtg gttccctaga ccaaaagtat taatatcaga caagaaccta ccgaatcaaa 31200 atatctgtga tgaggcccag caagctatgc tttaacaagt ttccgagtga ttctgatgca 31260 tgctaaggtt taggatccct tgtttttact cataagtcac tttctcatta aggccttccc 31320 tggccatcct atataaaatc tcatgttttc acaccgtcaa cttcgtattc ctcctcaata 31380 cttttatttt cctgatcact tatcactaac agcctctctc tctctctctc tctctctcta 31440 tgtatatata tatatatatc acttatcact gtctaacagc ctctctttat atatatataa 31500 tctatagatt atatatatat gcagcattgt gcaatcatta tcacgctcaa ttttaaaaca 31560 ttttcattgc cccacaaaga aacccaatcc ccttagccat cactccccat ttccccttcc 31620 cccagcacct agcaaactga tcatctacct acttgctgtc tataagattt gcctattctg 31680 gacattttgt ataaatagaa tcatacaata tgtggccttt tgtatctggc ttctctcact 31740 taatgttttc aaggttcatt catgttgtgg agtatatctg cactcatttc ctttttattg 31800 ccaaattgta tggatagaca ggtgttcctc aactgtgtcc tgataaaccc atctgaagtt 31860 gaaaatatca taagttgaaa atggatttac tactttgata aatctatcct aaagtcagaa 31920 aaatctcatg ttgaaccatc gtaagttgga taccatctga attacatttt tgttatccat 31980 tcactggttg acagacgtta ggttgtttcc actgtttgct ccttatttct cgtacctgaa 32040 atgtccttat tccctccctt cttatcccat gtttaagtca tttaagaccc agctcaaacg 32100 tcacctccac aaaaccttcc ttgatacccc tttcctcttc aattcacttg gaccttttgc 32160 atttaatttt aatttttatt ttttttaaga cagagtctca ctctgtcacc aggctggagt 32220 gcagtggtat gatctcagct cactaactac tctgcctccc aggttcaagc aattctcatg 32280 tctcagcctc ccaagtagct gggactacag gtgtgcgcca ccatgcctgg ctaattgtgt 32340 gtgtgtgtgt gtgtatgtat gtatgtatat atgtgtgtgt gtgtatatat atatatacac 32400 acacatatat aaatatatat acatatatat atatacacac atatataaat atatatacat 32460 atatatatat acacacacac acacatatat atatatatag tttttttttt ttttaagtag 32520 agatggggtt ttgccatgtt ggccaggctg gtctggcctc aagccatcct cccacctcgg 32580 cctcgcaaag tgctggtatt ataggcatga gccactgtgc ctggcctgca tttcatttta 32640 attataaaat attttgaact cagaaaaaag ggtatgctga atacctacgt acccacaaaa 32700 gtattaacat tttgccatat ttgcttctga tcttattttt tttgagaaat taaagatcat 32760 aatacaacta aagccccatt tctttccctt cattcccaga agtatgacaa ttatccttaa 32820 agttgatata tatcattccc atgcatgttt tttatacttc cctagtacaa gttagctgta 32880 tcctctgctc aggggctcat caagctgaat caagggactc atgatcctct tcaaagttcc 32940 ttcaggttgt tggcagaatt tagttccttg tgattgtagg actgagggcc cgttttctca 33000 ctggctgctg gccaggggtt gctcccagat atttaaaggc tcatgcccta gcccatgaca 33060 gtctcacaac atggcagctg acttcttcaa aaccagcagg agaatcttgc tctagtctac 33120 cacataacct aatcacagga gcggctatcc cgttattttc acagatcctg gtcacattca 33180 aggggaggga acccttctgt gtgtgtacac caggaggcag gaattttttt tttctttttc 33240 ttttttgtta aaaagtctta aagtctttta tccctaaagg aggcaggaat tttgagagcc 33300 atcagaattc tgcctaccac agcccagaaa tctgcatttt tcacaagtct ccagccatga 33360 tgtttctgat ggctcacact gctttattcc atttttaaag agtattttta ttgaaaagca 33420 ttagggttat ggtttaaaaa atattttccc taacaaagat gggtttgttt agagtcctac 33480 ttttgactaa atagctgaga ttcactttta tgtaaagtca ttttatagcg ttattaattt 33540 gggtgccttt aaaaatagta taaagcatgt ttctcgagtg tagtctgtta gccacctata 33600 ttggagagtt gggaggagag agtctctatc ttgaatttat gggaaaaatt ctaaaatact 33660 ttttataatg aaggacaaca tcataactcc ctaataaaat gtgcatgtat atattcaaat 33720 ttgctgtcat tgatcctgca cctacaaaat ccagtcctgg gggctggcat tcttactgct 33780 tgctgagggc cagatgatat agattccaga atatctccat gtagattttg gtgagaatta 33840 ctgtgctgaa aagaatgaca gtattgcagt tatacatggg ggttttggta ctttatattg 33900 tgactctgaa tttaaagcta tgcaatgtct tcttttttga aaggatataa ttgacactgg 33960 caaaacaatg cagactttgc tttccttggt caggcagtat aatccaaaga tggtcaaggt 34020 cgcaaggtat gtatgacatt ttgacacaga atattttcct catttgaagg gggattaagt 34080 gattgcttct ttttaaggat aaatgttttc aactgtcatt ttatcttcga aaagtaatgt 34140 aatctcatat aagacttaag atataatcct tttaaataat tttgtcatgt gttaataaag 34200 ctcataatta cagtcacttc cttgcctaat attaacattt ggtttttcag catgctaatt 34260 atatcagttt gtcctgaata gcatggcaga ggattttggg cccccttgca aaattaagaa 34320 taaggattcc aaagcgggtg aggaagtgat aggaaggggt gggccctgaa gatctggacc 34380 tcctggaatt gagtgatgaa tgctgcatct tctttgtgtc tgtagtgaaa ttttataatg 34440 cctgcttcct tttttattaa gtcggcctca cctcctcacc ttacctatgc tgttttactt 34500 ttgcttttat agttctacct gtgtttattt ctcattttcg tttcatctct caacaactct 34560 ggggtggcat tattattccc acttttcaga taaggttact gaggcatagg gaattgtcca 34620 aaggtacaga gctagtccgc tatagagatg agatttgaac ccagggaacc tggctcacag 34680 tttatgcttt tgctacctta agtttttaat agagtgacat caaacaaaca tttaagaata 34740 tgtttttctt ttccttttat aatttcatta aaaacattaa gtctctgatc agtctgcagt 34800 ttttatgtag gggtcaggta atgttctaac ttctgctttt tcctaagtga ttaacaggtt 34860 tttataagcc cttttgaaaa aatcacggta tctgtcgagc atctttgaat cagagtaagc 34920 cttctagtga gtcatatgtc agcagtttga ctgtatgggc ttttctaata tccagttcaa 34980 gtgtttatca gtgagttttt cttttaaata gatttgggac aggtactatg agagtatata 35040 agtgatacgt tataggacac taactagtat cctatgaaat ggcaaaaact gcaatcactt 35100 ttgcaccaac caaatagaaa ctaatcagtg cacttgctta tttttctaca tgctctttag 35160 ggttttaaat gtcaacctac tgtggcatag actttaatcc tctgggtatt cttttgttgt 35220 tctttcctgg tatatgctgt ggaattgaga tagactggtt cgtgagcgag agattttgtg 35280 ttgccacagg taggacatgc tcaaacaata cttgggtcat ttcttgaccc aagtcatcta 35340 ttcaccatag ttttgtagca ccgatcttgc atacatttca tgtatcttct ttgaacccca 35400 cgtcagtgct gcttatatga tactcagaaa ttaaacacta aggaataaga ttttcaggta 35460 ggattgagtt ttggagggtc acaaatcttg taatgtctaa tatttccact ctccctgctg 35520 agaattagtt ttggcttcct tggaggtgat atcgcctctg ttgagtataa gtggcctact 35580 gtgatcacac cactgcactc cagcctgggt gacagagtga gaccctgtct cagaaaaaaa 35640 aaaaaaaaaa aagaatgcat ggcctagatg acttctaagg tttttcccac ccagttccag 35700 ttttcatgtt ctaggcagag cagtaaagtg agaaacacat ggacttggga gtttagtctc 35760 gcatttcact gccacttaat ctgagcgact attccatatt taatctctct gaatgtattt 35820 actcatcttt aaaggggaat gattattaac atctttttct cagggaaact atatgagtca 35880 aggagataat atatttgaaa atctttttaa ctgcaaagcg ctgtttcact gttggttata 35940 atgtgattga tctcattgta gtgagcagct gcttaattgc gttttagaat gtagggaaga 36000 tagtaatatt tttcacatta tatatgtagc tggttctgga actgtaaaca tactcctttt 36060 ttatggagat ctgagtcacg taccataaaa ttcactcttt taaagttgta caatccagtg 36120 gtttttgata tattcagagt tgtgcatctg ctaccactat ttcattttgg aacccaaaga 36180 aaccttgtac ccattagcag tcattctccc ttctcccagc ccctggcaac tactaatcta 36240 ctttctacag aaagtccgta cagatttgtg tattatggac attccatata aatggactca 36300 tgcaatatcc tgtcttcttt cacttagcat agtgttttca aggttcatct aggttggggc 36360 atgtatcagt acttcatccc ttgttttggc tgaataatat ttcattgtac aaatatatca 36420 cattttgctt atccatctgt tggtgaacat ttgagtttct acctgttggc ttttatgaat 36480 aatgttgatt tgaatgtttg tgtacaagta tgaatacctg ttttcaggtc tcttgagtat 36540 atagttgcta ggtcatatag taactctgtg tttaacattt tgaggaattg cccgactatt 36600 taacaaggta tatgtactgt tttacaccag taacatatga gggttccaat atctccacat 36660 ccttgacaac acttgttact gtccttttta ttgtagccat cctagtggct atgatgtggt 36720 atctcattgt ggttttgatt tgtgtttctc tgatgctgat gatgttgaac atgttttcat 36780 ctgcttattg gccatttaca tatatcttct taagaacggt tacccattta cagtatggaa 36840 aatgcttcag atgcaactct agtcatgcct tagagatgga gctttattaa acattcagat 36900 ctctaggcat atgaagtgct gagttctctt gaactcctaa tacagattgc actgagttta 36960 gtgatacctt ttctggagca ttcctgagtt caggtaggga gaagggtttt tgctgtgatt 37020 ggcttgttat gttctttcta aatggaaata gaattgaagt gtctcctctc tccatttatt 37080 ggaagagtca tgagggacat aattagatga tcccttggag tctccggctt aggtcagtgg 37140 ttatctactt aggctgcaca ttggaatcac ctgagagtta aaaaaccagg ataacctctg 37200 cctgtgtctc atctccagca attctgatgt aattggtcag ggctgtggcc cgagtaggtg 37260 agttctggtt ttttaaagct cccaggtgat tctgatgtgc aatccaggtt gagatcactt 37320 tgggcccttt ccagctcttt aaacatatat atttatctag gaaggtatga aagcataagt 37380 tttcttgaga ctgcctttaa catctgtaaa ggctttcaaa gcagcttctg tagttttttt 37440 taaatggctg aatatttttc aacaggcagc atttgggtta taaaattagc ttttggtaga 37500 gttgacttat accacctcca gcttttgttc caaaaataaa tactggttct tttggcacac 37560 tagttgtttt accctaaagt tcctctttgt aagccagtta ttaaaagttg tgatgcagcc 37620 agggcgaagt ggtacacatc tgtagtccca gctactcgga aggctgaggg gggaggatcg 37680 ctagagccca agaagtcaag gctgcagtga actgtgatta caccactgca ctgcagcctg 37740 ggccacagag cgagactcat ctctttaaaa aaaagaatgt tgtgaggccg ggcgcagtgg 37800 ctcacgcctg tgatcccagc actttgggag gccgaggtgg acggatcacc tgaggttggg 37860 agttcgagac cagcctgacc aacatggaga aaccctgtct ctactaaaaa aaatacaaaa 37920 ttagccgggc gtggtggcac atgcctgtag tcccagctac tcggcaggct gaggcaggag 37980 aatcgcttga acctgggagg cagaggttgt ggtgagttgg gcgagccatt gcactccagc 38040 ctgggcaaca agagcaaaac tccatctcaa aaaaaagaaa agaaaagaaa agaatgttgt 38100 ggccaggcgc ggtggcttac gcctgtaatt tcagcacttt gggagaccga ggtgggcgga 38160 tcacgaggtc aggagatcaa gaccatcctg gctaacacag taaaacccca tctctactaa 38220 atacaaaaaa aaattagccg ggagtgctgg cgggtgcctg tagtcccagc tactcaggag 38280 gctgaggcgg gagaatggcg tgaacccagg aggcagagct tgcagtgagc ggagatcgcg 38340 ccactgcact ccagcctggg caacagagcg agattccgtc taaaaaaaaa aaaaaagaat 38400 gttgtgataa aaggtgatgc tcacctctcc cacacccttt tatagtttag ggattgtatt 38460 tccaaggttt ctagactgag agcccttttc atctttgctc attgacactc tgtacccatt 38520 aatcctcctt attagctccc cttcaatgga cacatgggta gtcagggtgc aggtctcaga 38580 actgtccttc aggttccagg tgatcaacca agtgccttgt ctgtagtgtc aactcattgc 38640 tgccccttcc tagtaatccc cataatttag ctctccattt catagtcttt ccttgggtgt 38700 gttaaaagtg accatggtac actcagcacg gatgaaatga aacagtgttt agaaacgtca 38760 gtcttctctt ttgtaatgcc ctgtagtctc tctgtatgtt atatgtcaca ttttgtaatt 38820 aacagcttgc tggtgaaaag gaccccacga agtgttggat ataagccaga ctgtaagtga 38880 attacttttt ttgtcaatca tttaaccatc tttaacctaa aagagtttta tgtgaaatgg 38940 cttataattg cttagagaat atttgtagag aggcacattt gccagtatta gatttaaaag 39000 tgatgttttc tttatctaaa tgatgaatta tgattctttt tagttgttgg atttgaaatt 39060 ccagacaagt ttgttgtagg atatgccctt gactataatg aatacttcag ggatttgaat 39120 gtaagtaatt gcttcttttt ctcactcatt tttcaaaaca cgcataaaaa tttaggaaag 39180 agaattgttt tctccttcca gcacctcata atttgaacag actgatggtt cccattagtc 39240 acataaagct gtagtctagt acagacgtcc ttagaactgg aacctggcca ggctagggtg 39300 acacttcttg ttggctgaaa tagttgaaca gctttaatat acaataattg ttgcattatt 39360 atttcagatg ataaatgtgg tcataagtaa gaaataaatg atcgagttta gtcttttaat 39420 tcactgtcct ttgaatacct gcctcttact ctggaggcag aagtcccatg gatgtgttta 39480 tgaacatggt tgaggaagat ttaggaagac tgcaacagta cactacctaa agcaggtttt 39540 ttactccatc tttttttgcc acgtacactg gcctcccact ttgatatgct tgaaattatc 39600 tccttgattt gtctttcaaa actacatatt gaggctggtt gcggtggctc acacctgtaa 39660 tcctagcact ttgggaggcc aagccggaca gatcacttga ggtcaggagt tcgagaccag 39720 cctggcaaac atgatgaaac cccaccttta ctaaaaatac aaaaattagc caggcgtagt 39780 ggtgtgtgcc tgtaacccag ctacctggga ggctgaggca ggagaatcac tggaacccgg 39840 gaggcagagg ctacagtgag ccaacatcac gccactgcac tccagcctgg gtgacagagc 39900 aagactctgt ctcaaaacaa aacaaaaaac aaaaaactac gtattaagac aagaaacaga 39960 ctgggcgcgg tggctcacgc ctgtaatccc agcactttgg gaggctgagg cgggcggatc 40020 acaaggtcag gagatcgaga ccatcctggc taacacggtg aaaccccgtc tctactaaaa 40080 aatagaaaaa attagctggg gtggtggcgg gcgcctatag tctcagctac tcgggaggct 40140 gaggcaggag aatggcgtga acccgggagg cagagcttgc agtgagcaga gatcgtgcca 40200 ctgcactcca gtctgggtga cagagcaaga ctccgtctca aaaaaaaaaa caaaaacaag 40260 aaacaaatta aactaatgtg atagactact gctttgtttt caaaagatac actccccaaa 40320 agttactgat ctaaaataca gtagtactat ctctgtttag taagaaccct gacaactaat 40380 agtgttctta tatgtaaaat gctattcttg cctttcattt cagaatatac tttttaaatg 40440 tgaatttctg gatttttttt tatagcatgt ttgtgtcatt agtgaaactg gaaaagcaaa 40500 atacaaagcc taagatgaga gttcaagttg agtttggaaa catctggagt cctattgaca 40560 tcgccagtaa aattatcaat gttctagttc tgtggccatc tgcttagtag agctttttgc 40620 atgtatcttc taagaatttt atctgttttg tactttagaa atgtcagttg ctgcattcct 40680 aaactgttta tttgcactat gagcctatag actatcagtt ccctttgggc ggattgttgt 40740 ttaacttgta aatgaaaaaa ttctcttaaa ccacagcact attgagtgaa acattgaact 40800 catatctgta agaaataaag agaagatata ttagtttttt aattggtatt ttaattttta 40860 tatatgcagg aaagaataga agtgattgaa tattgttaat tataccaccg tgtgttagaa 40920 aagtaagaag cagtcaattt tcacatcaaa gacagcatct aagaagtttt gttctgtcct 40980 ggaattattt tagtagtgtt tcagtaatgt tgactgtatt ttccaacttg ttcaaattat 41040 taccagtgaa tctttgtcag cagttccctt ttaaatgcaa atcaataaat tcccaaaaat 41100 ttaactgctt tatgaattca atttaaaaat ccttaaaata agtcctgtct ctttaaaaaa 41160 acctatgcat agttatcatt tctctacaaa ttaacctagt ttagttttct gttggttcca 41220 ttttccttgt ttgttaagtt ttagtagcta gtttaattgt aatctcaatg attatgtggt 41280 agaatgggtt ggcggagcta caaaaattcc tagctacttc agagacatta aatttcagac 41340 acatggtaca ctttatatta cattttacta tgctaaaata acacggcttt cttttggaat 41400 tctgttcagt ttttcagatt gtaatctcag ctacatctca acagattgtt ctcagatatg 41460 tcctattacc ttctttgtgt agatagtgct ttattgacta agaacaatga caacaacacc 41520 ttttgttttc tgggaatagg agaaaagttt taagccaaaa ctcttaattg cttatctgct 41580 ccacgtgagg tatgaactat caaacttagg agccatctag cttacacgtg ttccttaaaa 41640 agtttgctgt aggccgggca cagtggctcg tacctgtagt cccagcactt ttgggagccc 41700 agggtggggg atcacttgag ctcaggagtt caagaccagc ctgggcaaca tggcaaaacg 41760 ccatctctac aaaaatacaa aaaaaaaaaa aaacgctggg tgtggtggcg cacaactgta 41820 gtcccagcta cttgggaggc tgaggtggga ggattgcttg agcttgggag gtgaaggctg 41880 cagtgagcct tgacagtgcc actacactcc agcctggatg acagagtgag accctgtctc 41940 aaaaaaaaga gtttgctgta attcccagca acaaagtagg agactcaaac taaataattt 42000 tctatagtcc tagaacttct tagtttacaa aacattttta cttctgttat ctcatttgat 42060 cttcataccc atgtaaggtt gaggtagatg ttaccacatg tgagtgcaat atccagaact 42120 cctgaatccc cttcttcccc taaaatgtca gcccgctgag gtccacttgg ctaccctctt 42180 gaatactgca tccagcttcc cactgctgaa cctctttact cttttttttt cagttgcact 42240 taccaccttc tagtaagttg aaccatatga aattaccatt tttgcaggta aaaaatggcc 42300 ggtgataggc agtttggcgt cgtataaccc aataacatgt tatataattt acccacaagt 42360 ggtgggttgc tatgtcctgg aggagtcagc ttcagactct agctaaatga ttgtataacc 42420 ttgcagctct cccctaagtg aggaggcaat gttgaaagtc ccatgtctta tcagaaccag 42480 ggaggcagat gagaaactgc cttatggcag ctcccacaac atagggaggt gggtgacaaa 42540 tggccttggg acagcttctt cccaagactg gttatgttac agtgttcctg ggaggatcac 42600 atggcattcc tccaagatgg gtcagactgc tgttggcctt gtctgtgtgg cgtatgtgaa 42660 gacattcatg gcagagctgt tcccttagaa gcatctacta aattgatctt ttcctttctt 42720 acttactgtc tgtctccctt agtaggctgt cagctccgtg agtgcaggac cttgccagtc 42780 ctggtcactg ctatatcccc agcacctaca agagtgcctg gaaaattgta gtgctcaata 42840 aatatttgtt ggataaatga tagaatgata ggaagttaaa aagcaattaa aatacttgaa 42900 aagaagcaaa acatttttca tgttaagcaa aaaaaaaaaa aaaacttatt aaggatagct 42960 aacatgtatt gaattctata tgcaatggaa tgatacttag cgcctttgaa tccttatgat 43020 aaccctataa ggtaggttgt ttgggttttt ttaattgtcc caactttaca gatgaagaag 43080 tgcaggtcca gagaggtcac ataatttgcc caggatcaca cagctagtaa gtagcagatg 43140 aggaatttga acccaggcag ttgtattcca ccatctgccc tcttagttca ttgccactta 43200 acctataatg cccagctctt gtgtagaaat taatacactg ataacataga ggaaaacatt 43260 aagctcattg aatgtaataa gtccagatga cttgtacatt aaacacagct ttttgaggtc 43320 acagctgatc tctaagaatg taaactgatt tcctctggca ctaaaaagca ttttcaaaga 43380 ctgttaagag agtttctcca acattctctt cagatttttc tgctggctta ttttatgatt 43440 ctgtggacag cttcagacaa aataactttc tggtatgaag gattgtgttt actctgcttt 43500 tttttttgtt gttttttggg ttttttgttt tgttttgttt tgtttttgag acagtgcctt 43560 gctctgctgc tgcccaggct gagtgcaatg gcatgatctc ggctcactgc aacctctgcc 43620 tccctgggct caggccaggt gtatgctacc actctcagct aatttttaat ttattttttt 43680 agagatacgg tcccactctg tttcccaggc tggtctcaga actcctgggc tcagacagtc 43740 ccccgccatg gcctcccaca gtgctgggat tacaggcatc agccaccatg ctcagcttgt 43800 tctgccattt tcaaatgtga attttataga cactttaaac cacttgaaag agtgatgatg 43860 ttttaatgat tttcattatt atttgcaact tcaagcatta aacactgcca aattaagttt 43920 caagttttct ctttacacaa tatggatgta cttcataatg gacttcctca tcatgattaa 43980 tgagtgaagt gacattcaaa cttggtagct tttcagtaga acttcctttc ccaacatttt 44040 ttctgttcct ttaattatgg caatatctga gagctctgaa cataagtcaa aggtttgatt 44100 atttttcatg tggcttcctc tgcttggaac tttctgcccc gcatcttccc gttgccccct 44160 gtgtcctctt gtcatgcccc tacccttttt tgagtgtgtc tattttctgg cactacaaga 44220 cataacaggc tcatcttgtg ttttccctac cctgacccag aatcagccat tacttcaagg 44280 agccctggtt ccattattgg agaatactat tagaaaccag gatctggtgc taggcatgct 44340 catttctatt ggagtgtcat acaaacaatt tgtaaattgt ttgtaggtcc tcccagtgga 44400 taggattagg aaataaaaca tgcatactaa ccatgcatac acacacatct acgtctattt 44460 ctgtatctgt ctgtatacat attaaaataa acatgggttg ataactaatg tttctgctgt 44520 aatccacagc cttcatccta gcctgccact cttcttcttt ttagcttttt caacagtggg 44580 aaatgtggct cttgttatgt acactttatt cacttatttg tttgacccta gtatcataaa 44640 gtagttccgt atgcctgtaa cagatcgact aactagagtc cattatttgc ggaaagatct 44700 ttttgtccga agcgttaccg caggggtgtc caatcttttg gcttccctgg gccacactag 44760 aaaaagaaga attgtcttgg gccacacgta aaatacacta acactaacga tagctgataa 44820 gctaaaaaaa aaaaatcaaa aaaatttcat gatgttttaa gaaagtttac taatttgtgt 44880 tgggccacgt ttaaagccat cccgggtcgc aggttggaca agcttgcctt acagtatcca 44940 gtcaaaataa tgttttccaa aattacttct tttctttttc atccctttca gtgtggccgt 45000 tatttataat gcagtttggt tcattagtgt ttttattaca aatacaccct cagccttcat 45060 atcctagttt taatgaatta ttacggtgaa acataataag agtcagagct atacagaaag 45120 gtctactcag aggtgctttg ttccctccta ttctgttccc actactccta ctttccactg 45180 accctgtaag catcatattt atttttaatg gcagttacat ttttaccaag tgcttactat 45240 ctgtaggcac ttggtgtgta ttgcttcttt tggtgttcac agcaacctct tgaggtaagc 45300 actattatta tccccccttt ttcttttttc tttctttctt tctttttttt tttttttttt 45360 ttgacagtct tactctgttg cccaggcagg agtgcagtgg cgcaatctcg gctcactgca 45420 acctctgcct cccaggttca agtgattctc ctgcctcagc ctcctgagta gctgcgagta 45480 caggcacaag ccaccacgcc cggctaattt ttgtattttt agtagggatg aggttttgcc 45540 atgttggcca gggtggtctc gaactcctga cctcaggtga tctgcccgcc tcgacctccc 45600 aaagtgctgg gattacaggc acgaaccact gcacccggct attatcccca ttttttagat 45660 gagaaagctg aatcccagag agcataagaa gcttgtccag agtgacatct ctgatgcata 45720 accagtactc aaacctattt ttctgacacc aaggcctgtg tgtaaactgt aaaggggctg 45780 cttggcacct actttcctaa agttgtccta tcccttctct gtctgggtct tcctgaagct 45840 tggcacttct gaagtcacct ctctgaaaac attctggtaa ctgttaaatc ccttgttcta 45900 gctattcatg tgttctgtgt ggttaaacaa ggttcacaat gggccacctg gcctttggaa 45960 cttgggtgaa gaggctgcct tcagttgatc ctccccactc ccattttcaa aacatgggtt 46020 tacatgagtt atttgtgaat taggaaacat aaccatgttt tgagccttca tagaaaacaa 46080 acgtctgggg tcatacaggt taaaaggagt aaccaaattc ggcactatca ttgttctatt 46140 cagtagacaa ttctggggcc tttctgtgtc tcaggttctg tactagttgt ttcaggactt 46200 tgggataaat acaaactatc cctgccctca gggggcttaa ggtcaggtgt acaagtgact 46260 ctaatgtgag gcaaggctgg attcagtgct gcatatctaa tgctatggga attcaaagag 46320 gaagtgatca gaatgagaag ggagggatgg atcattccag gagaagcttc agggaaaagc 46380 aacatttaaa atgagacttt tgagagtgag ggaaatttgg acaggtggat atagaggatg 46440 caaggctaga ggaaaggttt tagccagaaa gtctgcttgg gcaaatgcct gggtaaaaaa 46500 agaaaatcca ctttgggagg acaaggcggg caatcgcctg aggtcaggag ttcgagacca 46560 gcctggccaa catggtgaaa ccccgtctct actaaaaata caaaaattag ctgggcgtgg 46620 tggtgggtgc ctgtaatccc agctacttgg aaggctgagg caggagaatc acttgaaccc 46680 aggaggcaga ggtttcagtg agccgagatt gcgccactgc actccagcct gggcaacaag 46740 agtgaaacat ctaaaaaaaa aaaaaagaaa atcacagggc agtgtgggga atggtgagta 46800 ttctaatttg gttgtggcag agaggatgta gaaggaagtg ataagagaga aagccggata 46860 ggagggcctt tgtgccagtt aggatgttct agacttccag ccaggttgcc cagctcaaac 46920 tggcttaaac aatgaggggg tttattggct atgtaattgg gaagtgcaga ggtagctcag 46980 gccagatcag tttgatccac tgctccatta tgatgtcaaa gacccatgcg atttccacct 47040 cattattctg ctgtccatag agccaacttc atcctaaggc cagtccttgt ggtcagacaa 47100 gggctgccaa tagtaatctg ggtgcaagtt tctttgagaa aatctttctg tgtcaactct 47160 cttaaaaggg gtgaaaaatc tctccttaag tcccactggc cagaatgggc ccatgcaccc 47220 atttcttaac cagtcactgg caactggggg tgggattgcc gtttgcccaa tcaggtccat 47280 ttctggagct aagattaaac tccatttccc ttgggacaca ttgaacagaa tcagaattcg 47340 atgaagaagg aagaagcgga gaattggttt ggtgttgggt aggcaaccaa aaataacctc 47400 tgttgcctca agtgccaaga aagtggtgtt ttgtgcttgt tagggtaaaa atggggatca 47460 tggaaaatat tttaagtttc atagaccaaa aaatattcca gtgtttcatc aaatctaaga 47520 ggctatcaat tataagatat accattattt tatgtaccac caaggaagaa aaaatgctgc 47580 cagtgaagtt aggatgtatt gcaggttggg ttctctggga agcaggctga aaaggaggtg 47640 agaatgcagg acatttatgg gagaacaccc ttgggattaa tactggagga ggagaaccaa 47700 gcagggttgg tggggcacag ggagaagttg ggatgccatg cagtcacaac aaaggcctca 47760 gccaacccca cggggagctc gagaagctga gatggccctt cagtgttgcc ctgccttgtg 47820 gtgagtgaat tgggtcttca tatccccatg ttgactggtc attggatgtg ggctccctta 47880 ggaatgggca tctcttcagc agaggtagct ttcttcaaaa gaggtgattc caaagagtca 47940 cccactcact gagggctgtc tgctggcagc attctcagcc actactcaaa gatgacctgt 48000 ccaggaaggg gaacctaggt ggcatgacac attgtctatt acaacatgct actgattata 48060 agagccggga ggtggggggc aacacaatgt ctgagatatt aaaatggaag tctcttagaa 48120 gaaatggata attctataat tatagttaat cagaaagggg aagaagtggg gaaatggacc 48180 aagggcctga gagagaaaac agacgcaaca ggccactaga aagataggac actggagggt 48240 gggaagccct agcagtttct tccagggtgg gctgggcacg gtggctcatt cctgtaatcc 48300 cagaactttg ggaggccgag gcgggcagat catttgaagt caggagttgg agaccagcct 48360 ggccaactcc tgtttcaccc tgtctctgcc aaaaatataa aaaattagcc gggtgtggtt 48420 gcatgcgcct gtaatcccag ctacttggga agctgaggca ggagaatcgc ttgaacccag 48480 gaggcagagg ttgcagcgag gaaaaatcgt gccactgcac ttgagcctgg gtgacagagt 48540 gagactgtct caaaaaaaaa aaaagtttct tccagggtgg cttctgtgcc agagtcaggt 48600 gccccagcta cctctaattt atggtcctcc tgcactggga aacagatttt ctacttttgg 48660 tttcatgata aataacattt ccccctgatt ttaaaagtta tggatttggc tgggcatggt 48720 ggctcatgcc tgtaatccta gcactttggg aggtcaaggc aggcagatca cttaaggtca 48780 ggagttccag accagactgg gcaacatggt gaaaacccgt gtctaccaaa aaaaaaaaaa 48840 aaaaaaaaat tagccaagtg tggtggtaca tgccagtagc cctagctact caggagactg 48900 aggtgggagg attacctgag cccaggagat caggcctgca gtgagctgtg attgtgccat 48960 tttactccag cctgggtgac agagtaagac cctgtctcaa aaataatagt aataggctgg 49020 gcgcggtggc tcaagcctgt aatcccaaca ctttgggagg ccaaggcggg cgatcaattg 49080 aggtcaggaa ctcaagaaca gccttgccaa aatggtgaaa ctccgtctct actaaaaata 49140 caaaaatgag ccgggtgtgg tggcgcatgc ctgcattccc agctactcag gaggctgagg 49200 caggagaatc gcttgaactc gggaggcaga ggttgcagtg agccgagatt gcaccactgc 49260 actccagcct gggtgacaga gtgagactcc atcttaataa taataaaata ataaaaattt 49320 taaaaagtta tggatctgga tggagggaaa tggaatgtat aaaagaagta aacatacaca 49380 agaagataca aatacagaat aaaagtaaaa tgcaaccatc atcccactac cccgatacca 49440 gggtatccgt ttttacatct tttctttcat tctttctgtc tttatataat tgtataaatg 49500 ctgcataaac ctcctcttgc ctgctgcctc ctcaaagacc tccctccctc cttcactgcc 49560 cttctgctcc tggagagcca ccctctctcc atttatcctt cctatcagct tcaggttctt 49620 accatgttaa caaaaagaaa atcttataag cctgtcactc tctacatacg ccgcacctcc 49680 tttcattcat agcctttaaa acatatatat agcagttatt gtggttattt ttctgttcac 49740 aaaataaaaa aacactcttt ctagaaaact ggaatataga ggcaagcttt tttttttttt 49800 cagacggagt ttcgttctgt cgcccaggct ggagtgcagt aacgaaatta cagcttactg 49860 taacctctgc ctcctgggtt caagatattc tcttgcctca gcctcctgag tagctgggat 49920 tataggtgcc tgccaccaca cccggctaat ttttgtattt ttagtggaaa tggggtttcg 49980 ccatgttggt caggctggtc tcgaactcct gaccttgtga tctgcccatc tcggccttcc 50040 aaagtgctgg gattacaggt gtgagccact gcaccctgcc gaggcaagat tttttttttt 50100 ttttttaaga aaacccagtt attccattac ccaatgaaac tctaaacatg ttgatgtaca 50160 tccttccaaa atttcttttt atgacaacat gctttttatt tttaattatt tttattttat 50220 tttaaggtcc ggggtacatg tgaaggatgt gcaggtttgt tacataggta aacgtgtgcc 50280 ttggtggttt gctgcacctg tcaacccatc acctacgtat taagccccac atgcattagc 50340 tattgatcct gatgctctct ctccctgctg gctccccagc aggccccggt gtgtgttgtt 50400 cccctccctg tttatgagaa cactttcttg acataaagat ttcatttatt cccatggaat 50460 tctaaaggct tttcatactt gtgaaggaat aatagtttag aaataaactg aactttaaaa 50520 gataccattt tgaaaaataa tatacagcca tcaaaaatta tatttatggg aactatgcaa 50580 taatattaaa ctctatcatc tgttgactgc ctcctatatt ccagaaactt tacatacacc 50640 aattctaatc cttacaagaa cgctgtgtag gctttagcat tagatggacc aggtttcacc 50700 aactgtatgg tcttggataa gtacccaacc tcctgtccct aagtttcctc acctgtgaaa 50760 acacggtttc taccagcttt caaataagat gatcaatata aggcacttgg aacagaacct 50820 gacacatcat aagcactcta taaatgtcta ttatcaccaa ataattccag gtgccttgaa 50880 aatttaaatg aaaaacaaaa tcaaaccatg acaatactag aagcaaattt aggtgaacac 50940 ttttctaatc cgggggtggg cgggggctgg ggggaggcag ggagaagacc tttttttttt 51000 ctttttgaga tggagtcttg ctctgtcccc aagctggagt gcagaggcgt gatctcagct 51060 cactgcaacc tctgcctcct ggattcaagt gattctcctg cctcagcctc ccgagtagct 51120 gggactatac aggtgcacac caccacggcc agctaatttt tgtattttta gtagagatgg 51180 ggtttacacc ctgttagcca ggatggtctc aatttcttga cctcgtgatc ccatccgcgt 51240 tggccttcca aagtgctggg attaccagca tgagccaccg tgcccggctg ggagaagacc 51300 tttctaagca tgataccaaa ggcagagaca ataaaggcaa agaattgaca gaattcacta 51360 tccgataaaa atcacttctg tggccgggcg cggtggctca cacctgtaat cccagcactg 51420 ggaagccgag gtgggcggat tgcttgaggc caggagttca agaccagcct ggccaacatg 51480 gcaaacctcc tgtctctact aaaaatacaa aaaattagct aggcatggtg gcatgcctgt 51540 agtcccagct actcaggaag ctgaggcatg agaatcactt gaacctggga ggtagaggtt 51600 gcagtgagcc aagatcatgc cactgcactc caacctgggt gacaaagtga gactctgtct 51660 caaaaaaaat aacaattaaa ataaaatcac ttctgaatgg tggaaagcac cacaaagtta 51720 gaggtcaagc aataatttgg agaaaagaat tagtaatttg ttggacagac aaaagacttt 51780 tttaatataa caaaaacttt aaaaattaaa aaaatacaca ttcgaggaca ttttcctaaa 51840 aacacaggca aaggacataa acagcaaagc aagaagacag cttgatgtgg ccattttatc 51900 cagggggaca ttttggtgag ccctatggac acagctgcca tgatgccaac aatgtgacag 51960 ctgtcccctt caaaatgcgt tagccccagc tcttcctctc ccccaacctc cagtccaaag 52020 gacttgcact ttctacttta ctcctttctg cattgtttaa ttttctttta caaatatgtt 52080 acttgtcatc agaaaaaata aagaaataaa taaactgtta gagtgttagc cccttaaagg 52140 ggagcaagaa tcacctttct aaaagaaagt ttatgttaaa tataatatta gcatatgtga 52200 atcctgagag aaaagttaac agtttagttg agttatttcc tctgtagtct ggagctaaaa 52260 atagggaatc ttattctgtc ctaaatcttt tccttcctcc acccagtgtc tgtctggatc 52320 gaattcattc attcactcag taggcactca ctcagccagg catggtgcta ggcctcagga 52380 cctcgctgtg aaccagaaac tgtccctacc cccatggtgc aggcattctg cttgggagtt 52440 ggaggaggaa caggtaaaaa ataattaaat attcaggtta acgatatatt gtcaggtttg 52500 aggattgagg aaagggcgca gagagtggca agggctgctg ttttagatac agtggccagg 52560 aggcctccga tgaggtgacc tttgaggaga gacatgcagg agatgagggg acagtgaaga 52620 ggatttctaa gaacactcca ggcagacaga acagcgacag ccaaggccct gaagtgggta 52680 ggggcctggt gtgtgtgagg aacctcagga ttgccatcat ggctggagca gagacatgaa 52740 gcaagaaggc catggagatg agggcaggga gatcccggag tggggagatc agatggggct 52800 ctgtgtatca tgcaaaggac tttgcattct gttccaagag ctgggaaggt tgacataatt 52860 aggaaaaaag cccagaaaag cagaggtatc catttttcat ggtaaagatg ataatttcaa 52920 ttaaaacacg attcctggat atatgtaatt tgtaggccaa atggtgccca atccctacct 52980 ccctcacccc ctcacttccc tatccctaaa acctgtacct caactcccgt tcgtaagtga 53040 tgggagttag gaatagagaa atctcccggt tgggttttct gagcaaagag gtaacatagc 53100 agctctgtta tttctttcac gtctccaagg gaaccatgac tcacccttag ctatcccccg 53160 ggaatgtggc cctcagagtg ttcttttact gattcgtgat tttgttatgt acacctggag 53220 tgatggaaca taccatacca gcttgtcagg gttgctttgt gcaaagatcg atgacgtgtg 53280 tgaacccgga tccatgcttg gggtcctgag tttcaggtgc catggccagt tgctagcagg 53340 ttgtatgtgt gtgaccagcc cctatgtgag tctctcagac cctgaaactc caaacaggct 53400 tccctgggca gagacattct gtccatgctc tgtggcttgc tgctcgagag ggatagatca 53460 catcctgtgt ggcttcttct taaatgaaga aggacattgg aagcctgtgc tgggcttctc 53520 tggacccccc gatgtatatg tatgtatatt aaagagagac cagggtctca ctctgttggc 53580 caggctggtc ttgaactgct agcctcaaga aatcctcccg ctttggcctc ccaaagtgct 53640 gggattacag gcatgagtca ccatgcctga tgtatatatt tttccagctc ccttcttttc 53700 tgtatcattt gctattacta cctcttagct attagtataa actgatcttg agttgtgtaa 53760 atctttctgg tgattcactg tgatgggatg attgtgtcct ctcaaaattc ctatgttgga 53820 gtcctgaccc atggtacctc agaaagtgac tgtatttgaa gataggtctt taaagaggtc 53880 attgtaaatt aattaataag gtcattaggg tggactctaa tccgatatga ctggtatcct 53940 tataagaaaa ggaaattagc acacagacac acaatcagag ggagaagaca gccagtcatc 54000 tacaagccga ggagacagac ctcagaagaa accaaccctg cctgcacctt gatcttggac 54060 ttctagtcgc cagaactgtg agaaaacaaa tctcatgttt aagccagaac ctagcacgtg 54120 gtacttgtta aggcatccct agaaaactaa tacactcact gaatgaggca ggtagctgtt 54180 tcttttattt tttgagacag agtctcactt tgtctccaag gccagagtgc agtggagcga 54240 tcacagctca ctgcagcccc tgccttccag gctcaagcca tcctcccacc tcagcttctc 54300 aagtagctgg gactacaggc atgcaccacc acgcccagct aatttttgta tttttttttt 54360 ttttttgtag agacggggtt caccgtgttg cctaggctgg tctcaaaccc ctgagctcaa 54420 gcaatctgcc ctccttggcc tcccaaagtg ttggatttac aggcgtgagc cactgtgcct 54480 ggatatggta actttttcat atgctatttg cttgatgatt atttttctgt ttctgatata 54540 atgcttttta ttagagagtt atctgtttgt ttttattttt taatgtttga atttaaaaaa 54600 ttagtataat ttgcataatt gaaaaattat atttgaataa ttgaaatata tttgtataac 54660 cttaaattta aaaactatga tagcgtatac agtgaaattt tcctctcatc ccttttttcc 54720 atttaaccag tgcacttccc aacagccaac agataatttt agtttcctca ctccctgagc 54780 tattttatgt atatgcaagt agatatgtac atacatattt ctgccttgta acacaaatag 54840 tagcatacta tacaactgct ctgcttcttc ctttttttag ctaagaatat taaaagagtg 54900 aaaaagatgt acgctaacaa aaatcaaaag aaaactagag tgacattata agaactgatg 54960 atgtagattt cagagcaatg attactgcta ggaaaaaagg gtcattttac attgatcaaa 55020 gaggtcaact catcaggaag acataataat cctaaacact tatgtactta acagagcatc 55080 aaaatacatg aagcataaat gaaagaaccg tgggagaaag tagacaaatt aatgactgta 55140 gttgaagatt tcagtatccc tctatgaaaa tcagggtagt acaagtacac agaaaattgg 55200 taaagatata tgacttgaac aacattatca accaaattga cctcatttac atttgtggaa 55260 tgttccaact aagaacgtca gaaaacatac tcttttcaag tgcacatgga acatttacca 55320 agatagacaa tattttgggt caccgcaagt ctcaacacat tgaaaggatt cagatcatat 55380 aaagtatgct ccatgaccat gatggaattg aattagaaac caataatgta tctctggaaa 55440 atacacaaat atttggaaat taatatgcct tctaaaaaat ttatgcatca agaagaaatc 55500 aaaagggata tttgaaagta ctatgaactg atggccaggc atggtggctc acgcctgtaa 55560 tcccagcact ttgggaggcc gagaaagatg gatgaagtca ggagttcaag accagcctgg 55620 gcaacatggc agaaccccgt ctctactaaa aatacaaaaa attagccggg cgtggtggtg 55680 ggcgcctgta atcccagcta ctcaggaggc tgaggcatga gaatcgcttg aagctgggag 55740 gtggaggttg cagtgagcca agatcacgcc actgcactcc agcctgggca acaagagtga 55800 aactcggaca aagaaagaaa gaaaagaaag agagagagaa ggaaggaagg aaggaaggaa 55860 ggaaggaagg agggagggag ggaaggaggg aaggaaggaa ggaaggaaag aaggaaggag 55920 ggagggaggg aaacaaaaaa gaaaaagaaa gagaaaaagg gaggaaagaa agaaaagaaa 55980 gaaagaaaaa gaaagaaaga aaagaaagaa actaactcac catttagtaa ccatagtagt 56040 aataactgat ttgggcaaga gtcatcaatg ggtgaaagct tgatgaggaa taggatactt 56100 atataccccc aaacaaagcc acaaattatt aataacaaag gggaaagtag taattttaca 56160 atggcaagac accactgtaa acggataatg aaagaacatc aacaataatg ggaaaaaaat 56220 gatgcaattt acctcctgct atgctgctct gagaacaagc ataatttctg tggtagtcct 56280 ccaaaaatgc ataacctgag tctgttcgtg gggaggcatc agataaaccc aaattgaggg 56340 acattgtaca aaacaactgg cctatatgca tcaaaaatgc caatgtcaca aagtctgggg 56400 aactctcccc agttcaggag acaattaaat gtaatgtgtg atcctggact gtgaaaaaag 56460 taactataaa ggatggtatt gaaacagttg tcaagattgg agtatagtag taacaaatca 56520 aggctaaatt ttcttattgt actgtcgtgt gtaaaagaat gtctttgtta gaaaatacac 56580 actgaaatat ccacaggtga aggagaacaa tagctccaat ttacaaatgc ttctgaaaaa 56640 atatatatat acacacacac atacagagag aaggcaagtg ataaagcaag tggggcaagt 56700 ttttttaaac tggtgaatct gggtaaagga tattcaggaa ttctttgtac tattgttgca 56760 acatttctgt aagtttgaaa tttaaagttt aaaaagaaag agaggccgga ctcagtggct 56820 cacgcctgta atgccagcac tttgggaggc cgaggcgggc ggatcacgag gtcaggagat 56880 cgagaccatc ctggctaaca cggtgaaacc ccgtctgtac taaaaataca aaaaattagc 56940 cgggcgtggt ggcgggcgcc tgtagtctca gctactcggg aggctgaggc aggagaatgg 57000 tgtgaacccg ggaggcggag cttgcggtga gccgagatcg tgtcactgca ctccagcctg 57060 ggcgacagag cgagactcca tctcaaaaaa aaaaaaaaaa ggagagagaa ggcataaaca 57120 atattaaaaa taaaacagaa cattactata gacgtagtag agattttaac gatcatgaag 57180 aaaatactag aaataagtct ttatgtttta ttttatttta ttttatttat tattattatt 57240 ttttgagatg gagtctcatt ctgtagccca ggatggagtg caacggcgcg atctctgctc 57300 actacaacct ccgcctccca ggctcaagct attctcctgc ctcagcctcc caagtagctg 57360 ggattacaga aaagcgccac cacgcccaac taatttttgt atttttagta gagatggggt 57420 ttcaccatgt tggccaggct tatcttgaac tcctgacttc aggtgatcca cctgccttgg 57480 cctcccaaag tgctgggatt acaggcgtaa gacaccgcgc caagcccttt atcttttaga 57540 tgtatatact gagatactta tcataaaatg gtgggatatc tgggatttcc ttgaagataa 57600 tccagggcgc caggtatggt ggctcacacc tgtaatccca gcactttggg aggccaaggc 57660 cggaggatca cttcagctca ggagttcaag atcagcctgg gcaacatggg gaaaccctgt 57720 ctctattaaa aatacaaaaa gtagctaggt gcggcggtag cacatgcctg tagttccagc 57780 tacttgggag gctgagttgg gaggatcact taagcctagg aggtagagat cagcttcagc 57840 aacatggcaa aaccccatct ctacaaaata tacaaaaatt agctggactt ggtggtgcac 57900 acctatagtc ctagctactt gggaggctga ggtgggagga ttacttgagc ccaggaggta 57960 gaggtttcag tgaaccgaga tcgtgtgact gcactccatc ctggatgaca gagtgagacc 58020 ctgtctcaaa aaaaaaaaca aaactgcact cttttatgta tttttatact tttgaaatgt 58080 tctataatat ttttgaaatg ttctataata agagaatatt gtgaagactt tatagaaata 58140 catttgagaa cctaaataga gtaaattact agaatcaaac taaggaaaaa atggaaaatc 58200 tgaaaaaaat gcaataatca ttaaagagat tgaattgtca tttgaaagtc tgtcctcaca 58260 aaagacctcc ttcctctact gtggtcagca tctttggcat acatgagata aaatgtatgg 58320 tccagtccag cctctaagcc tgtgcaattc attcagtcat tcagcaaata tctattgaat 58380 actacgtatg ggccaggcac tcttctggct accggggata cataagtgaa caacaacaac 58440 aacaacaaca acaaaggaaa aatgtctcta attttgtggc acttaatata caacaaataa 58500 taatgaataa gtgatatata gtatgttagg aggagaacat tactatggaa aaatagagga 58560 ggataaagga gactgagagg cagaaggatg ggccagtttg taatttgaaa ggcaaggttg 58620 taggcaaggt tcagattgga acactgaaac acggatttcc cacagaaatg aacaggtctc 58680 cttggagaga tggctaattc aaggtctggg tcaagaagtg tacaggaaga gcctggaaca 58740 ttttgttgca ccaaaaagat aaaacagaac aaaacaaaac tcggttaatt agttactgtt 58800 ggaagatgct agcaagccag ttctttagtg atttttaaaa gacagataat tataaggaaa 58860 ctttttaata aacaagcatt tatactgttt tcgacacaga ctaccactga ctactcaaat 58920 aatacatgag gggatatttc tttttatgga agtattctgg ctaataagaa gaatagaatt 58980 aatcaccagt ggctgccagc accacaaaaa gagatacaac tagatcttat gtgttttaca 59040 atttttttat atttgggggg ctggtctctt atatgtctct tttggagaaa cagcccacca 59100 cctggattca tctcctaggg cttccataac aaagtaccat aaaatgagtg tcttaaaaca 59160 acacatggcc gggcacagtg gctcatgcct ataatcccag cactttggga ggccgaggcg 59220 ggcagatcac ttgaggttag gagtttgaga ccagcctggc caacaaggtg aaaccccgtg 59280 tctactaaaa atacaaaaat tagccagaca tggtggcggg cacctgtaat cccagctact 59340 caggaggctg aggcaggaga atcgcttgaa cctgggaggc tgaggttgca gtgaggtgag 59400 atctcgccat tgcactccag ccttggcaac agagcgagac tccatctcaa aaacaaacaa 59460 acaacaacaa caacaaaaca ctcacgttta ttctctcaaa gttctggagg ctaaaactct 59520 gaaatcaagg tgtcaataga gctgtgctcc ctccaaaggc tttaggggag gatccttcct 59580 tgcttcctcc tagattctgg tggtttctgg caagctttga tattctttgg cttatgactg 59640 cataattaca acctctacct ccatattcat gtggccatct tccctctatg ggtgtctgtg 59700 tccaaatttc cctcttatgg acaccagtca tattggatta ggcttcccct aatccagtat 59760 gacctcatct taacttgatt acatctacaa aggccctatt tccaaataag gtcacattca 59820 cagattccag gtagacatga aatttgggta acactattta acccagtata ccacctatga 59880 agtattcttt ttatttttct cctcagcttt tattttaagt tctggggtac atgtttagga 59940 cgtgcagttt gttacataag taaacgtgcc atggtggttt gctgcacaga tcaacccatc 60000 acctaggtat taagcccagc atccattagc tatttttttc tgatgctctc ccaccacccg 60060 ccccgccccc gacaggcccc agtgtgtgtt gttcccctcc ctgtgtccat gtgttctcat 60120 tgttcagctc ccacctataa gtgagaacat gcagtgtttg gttttctgtt cctgcatttg 60180 tttgctgagg ataacagctt ccagctccat ccatgtccct gcaaaggaca tgatcttctt 60240 cttctttttt atggctgcat agtattctga agtattcttg acaaaaagaa aaaatcaacc 60300 tgaatctatt caagcctcta gagtcaacta aaaatttaca gaaaatacag gagactgagt 60360 aacgtgttaa atgacatcac agggatgcaa ttagccaact ccagactatg ggaaactcta 60420 caggacaaac tacctggtat cttcaacaaa taaattgcag ggaataaaga catgatggag 60480 gaacctagac taaaagagac ttaaagatga accagtagct atgtttggac ctcatttgga 60540 tcccaattca aacaaacttt aaaatacaca cccatttatg acacttatga gacaattgga 60600 gatttgaaca ctgacttgaa tatccattga tattaaggaa ttatttttga aaatgcggaa 60660 taatactaag gctatggttt tttttagaga gtccttatct tttagaaaca tatactaaat 60720 ttgcagataa aaatgacttg atgttgggga tttgtttcaa aataatatgg gagttggggg 60780 atgtgggtgc agatatggct gtgacaagat ggttcatggg ctgataattg ttgaagctgg 60840 gtgatgggta catgtgggag ttcatgatac tatattttta tgtgtttcaa tctttccata 60900 ataaaatttt tttttagaaa aaagaaagaa aggaaagaag gaaagaaaga aaagaaagaa 60960 agaaagaaaa agaaaagaaa gaaagaaaga aagaaaaaga aaaagaaaga aagaaagaaa 61020 gaaagaaaga aagaaagaaa gaaagaaaga aagaaaaaat acggtatcag gataagccta 61080 aataagaagg tgacatttgc tgtggatcgt tcagcatgta cagggcccct gtcaccatct 61140 ggctttaaaa atactaaaaa ataaatcttg tgtaggggct gtgagagatt aaagacggcc 61200 acaaattctt tttttaaccc aattctccca taccatttat tttaaaattt atgcattttt 61260 attaattaat ttatttatgt atttagtttt agagacaggg tctcgctatg ttgcccagac 61320 tggccttgaa ctactgggct caagtgatcc tgcctcagcc ttctgagtag ctgtaactac 61380 aggtgcccac cactgtgact agcctctgcc acaaatgctt ttctaattct ccccttacct 61440 aaagctaatt cccctccctt tgaatttggc ctggccttag agactggctt gaccaataga 61500 tggcagcaga agtgaagttc cagggcttct gaggctaagt cataagaag 61549 <210> 27 <211> 20 <212> DNA <213> Homo sapiens <400> 27 gaatgatatg tctctcccga 20 <210> 28 <211> 20 <212> DNA <213> Homo sapiens <400> 28 caagcaacca aaggcagctc 20 <210> 29 <211> 20 <212> DNA <213> Homo sapiens <400> 29 ccccacccaa atctcatctt 20 <210> 30 <211> 20 <212> DNA <213> Homo sapiens <400> 30 cgaggcgggc agatcacgag 20 <210> 31 <211> 20 <212> DNA <213> Homo sapiens <400> 31 ctacttatat ccttttgaaa 20 <210> 32 <211> 20 <212> DNA <213> Homo sapiens <400> 32 ggtatgtttc atccactggc 20 <210> 33 <211> 20 <212> DNA <213> Homo sapiens <400> 33 cctcagcctc ccgagtagct 20 <210> 34 <211> 20 <212> DNA <213> Homo sapiens <400> 34 tttaagaagg agagcaagtg 20 <210> 35 <211> 20 <212> DNA <213> Homo sapiens <400> 35 cttacaaaat tcaagggcca 20 <210> 36 <211> 20 <212> DNA <213> Homo sapiens <400> 36 aagttcaatt ttcgctaagt 20 <210> 37 <211> 20 <212> DNA <213> Homo sapiens <400> 37 aaaatgtctc tggacactga 20 <210> 38 <211> 20 <212> DNA <213> Homo sapiens <400> 38 agagagagag agagagagag 20 <210> 39 <211> 20 <212> DNA <213> Homo sapiens <400> 39 gcctaggcaa aaaaaaaaaa 20 <210> 40 <211> 20 <212> DNA <213> Homo sapiens <400> 40 tatcattatc ttattttttc 20 <210> 41 <211> 20 <212> DNA <213> Homo sapiens <400> 41 tttttatgca aagaatatga 20 <210> 42 <211> 20 <212> DNA <213> Homo sapiens <400> 42 agtctaaaag cttactttaa 20 <210> 43 <211> 20 <212> DNA <213> Homo sapiens <400> 43 tggcaattcg ttacagcatc 20 <210> 44 <211> 20 <212> DNA <213> Homo sapiens <400> 44 tgatgatgtt tgcacaaccc 20 <210> 45 <211> 1152 <212> PRT <213> Homo sapiens <400> 45 Met Ala Leu Arg Val Leu Leu Leu Thr Ala Leu Thr Leu Cys His Gly 1 5 10 15 Phe Asn Leu Asp Thr Glu Asn Ala Met Thr Phe Gln Glu Asn Ala Arg 20 25 30 Gly Phe Gly Gln Ser Val Val Gln Leu Gln Gly Ser Arg Val Val Val 35 40 45 Gly Ala Pro Gln Glu Ile Val Ala Ala Asn Gln Arg Gly Ser Leu Tyr 50 55 60 Gln Cys Asp Tyr Ser Thr Gly Ser Cys Glu Pro Ile Arg Leu Gln Val 65 70 75 80 Pro Val Glu Ala Val Asn Met Ser Leu Gly Leu Ser Leu Ala Ala Thr 85 90 95 Thr Ser Pro Pro Gln Leu Leu Ala Cys Gly Pro Thr Val His Gln Thr 100 105 110 Cys Ser Glu Asn Thr Tyr Val Lys Gly Leu Cys Phe Leu Phe Gly Ser 115 120 125 Asn Leu Arg Gln Gln Pro Gln Lys Phe Pro Glu Ala Leu Arg Gly Cys 130 135 140 Pro Gln Glu Asp Ser Asp Ile Ala Phe Leu Ile Asp Gly Ser Gly Ser 145 150 155 160 Ile Ile Pro His Asp Phe Arg Arg Met Lys Glu Phe Val Ser Thr Val 165 170 175 Met Glu Gln Leu Lys Lys Ser Lys Thr Leu Phe Ser Leu Met Gln Tyr 180 185 190 Ser Glu Glu Phe Arg Ile His Phe Thr Phe Lys Glu Phe Gln Asn Asn 195 200 205 Pro Asn Pro Arg Ser Leu Val Lys Pro Ile Thr Gln Leu Leu Gly Arg 210 215 220 Thr His Thr Ala Thr Gly Ile Arg Lys Val Val Arg Glu Leu Phe Asn 225 230 235 240 Ile Thr Asn Gly Ala Arg Lys Asn Ala Phe Lys Ile Leu Val Val Ile 245 250 255 Thr Asp Gly Glu Lys Phe Gly Asp Pro Leu Gly Tyr Glu Asp Val Ile 260 265 270 Pro Glu Ala Asp Arg Glu Gly Val Ile Arg Tyr Val Ile Gly Val Gly 275 280 285 Asp Ala Phe Arg Ser Glu Lys Ser Arg Gln Glu Leu Asn Thr Ile Ala 290 295 300 Ser Lys Pro Pro Arg Asp His Val Phe Gln Val Asn Asn Phe Glu Ala 305 310 315 320 Leu Lys Thr Ile Gln Asn Gln Leu Arg Glu Lys Ile Phe Ala Ile Glu 325 330 335 Gly Thr Gln Thr Gly Ser Ser Ser Ser Phe Glu His Glu Met Ser Gln 340 345 350 Glu Gly Phe Ser Ala Ala Ile Thr Ser Asn Gly Pro Leu Leu Ser Thr 355 360 365 Val Gly Ser Tyr Asp Trp Ala Gly Gly Val Phe Leu Tyr Thr Ser Lys 370 375 380 Glu Lys Ser Thr Phe Ile Asn Met Thr Arg Val Asp Ser Asp Met Asn 385 390 395 400 Asp Ala Tyr Leu Gly Tyr Ala Ala Ala Ile Ile Leu Arg Asn Arg Val 405 410 415 Gln Ser Leu Val Leu Gly Ala Pro Arg Tyr Gln His Ile Gly Leu Val 420 425 430 Ala Met Phe Arg Gln Asn Thr Gly Met Trp Glu Ser Asn Ala Asn Val 435 440 445 Lys Gly Thr Gln Ile Gly Ala Tyr Phe Gly Ala Ser Leu Cys Ser Val 450 455 460 Asp Val Asp Ser Asn Gly Ser Thr Asp Leu Val Leu Ile Gly Ala Pro 465 470 475 480 His Tyr Tyr Glu Gln Thr Arg Gly Gly Gln Val Ser Val Cys Pro Leu 485 490 495 Pro Arg Gly Arg Ala Arg Trp Gln Cys Asp Ala Val Leu Tyr Gly Glu 500 505 510 Gln Gly Gln Pro Trp Gly Arg Phe Gly Ala Ala Leu Thr Val Leu Gly 515 520 525 Asp Val Asn Gly Asp Lys Leu Thr Asp Val Ala Ile Gly Ala Pro Gly 530 535 540 Glu Glu Asp Asn Arg Gly Ala Val Tyr Leu Phe His Gly Thr Ser Gly 545 550 555 560 Ser Gly Ile Ser Pro Ser His Ser Gln Arg Ile Ala Gly Ser Lys Leu 565 570 575 Ser Pro Arg Leu Gln Tyr Phe Gly Gln Ser Leu Ser Gly Gly Gln Asp 580 585 590 Leu Thr Met Asp Gly Leu Val Asp Leu Thr Val Gly Ala Gln Gly His 595 600 605 Val Leu Leu Leu Arg Ser Gln Pro Val Leu Arg Val Lys Ala Ile Met 610 615 620 Glu Phe Asn Pro Arg Glu Val Ala Arg Asn Val Phe Glu Cys Asn Asp 625 630 635 640 Gln Val Val Lys Gly Lys Glu Ala Gly Glu Val Arg Val Cys Leu His 645 650 655 Val Gln Lys Ser Thr Arg Asp Arg Leu Arg Glu Gly Gln Ile Gln Ser 660 665 670 Val Val Thr Tyr Asp Leu Ala Leu Asp Ser Gly Arg Pro His Ser Arg 675 680 685 Ala Val Phe Asn Glu Thr Lys Asn Ser Thr Arg Arg Gln Thr Gln Val 690 695 700 Leu Gly Leu Thr Gln Thr Cys Glu Thr Leu Lys Leu Gln Leu Pro Asn 705 710 715 720 Cys Ile Glu Asp Pro Val Ser Pro Ile Val Leu Arg Leu Asn Phe Ser 725 730 735 Leu Val Gly Thr Pro Leu Ser Ala Phe Gly Asn Leu Arg Pro Val Leu 740 745 750 Ala Glu Asp Ala Gln Arg Leu Phe Thr Ala Leu Phe Pro Phe Glu Lys 755 760 765 Asn Cys Gly Asn Asp Asn Ile Cys Gln Asp Asp Leu Ser Ile Thr Phe 770 775 780 Ser Phe Met Ser Leu Asp Cys Leu Val Val Gly Gly Pro Arg Glu Phe 785 790 795 800 Asn Val Thr Val Thr Val Arg Asn Asp Gly Glu Asp Ser Tyr Arg Thr 805 810 815 Gln Val Thr Phe Phe Phe Pro Leu Asp Leu Ser Tyr Arg Lys Val Ser 820 825 830 Thr Leu Gln Asn Gln Arg Ser Gln Arg Ser Trp Arg Leu Ala Cys Glu 835 840 845 Ser Ala Ser Ser Thr Glu Val Ser Gly Ala Leu Lys Ser Thr Ser Cys 850 855 860 Ser Ile Asn His Pro Ile Phe Pro Glu Asn Ser Glu Val Thr Phe Asn 865 870 875 880 Ile Thr Phe Asp Val Asp Ser Lys Ala Ser Leu Gly Asn Lys Leu Leu 885 890 895 Leu Lys Ala Asn Val Thr Ser Glu Asn Asn Met Pro Arg Thr Asn Lys 900 905 910 Thr Glu Phe Gln Leu Glu Leu Pro Val Lys Tyr Ala Val Tyr Met Val 915 920 925 Val Thr Ser His Gly Val Ser Thr Lys Tyr Leu Asn Phe Thr Ala Ser 930 935 940 Glu Asn Thr Ser Arg Val Met Gln His Gln Tyr Gln Val Ser Asn Leu 945 950 955 960 Gly Gln Arg Ser Leu Pro Ile Ser Leu Val Phe Leu Val Pro Val Arg 965 970 975 Leu Asn Gln Thr Val Ile Trp Asp Arg Pro Gln Val Thr Phe Ser Glu 980 985 990 Asn Leu Ser Ser Thr Cys His Thr Lys Glu Arg Leu Pro Ser His Ser 995 1000 1005 Asp Phe Leu Ala Glu Leu Arg Lys Ala Pro Val Val Asn Cys Ser 1010 1015 1020 Ile Ala Val Cys Gln Arg Ile Gln Cys Asp Ile Pro Phe Phe Gly 1025 1030 1035 Ile Gln Glu Glu Phe Asn Ala Thr Leu Lys Gly Asn Leu Ser Phe 1040 1045 1050 Asp Trp Tyr Ile Lys Thr Ser His Asn His Leu Leu Ile Val Ser 1055 1060 1065 Thr Ala Glu Ile Leu Phe Asn Asp Ser Val Phe Thr Leu Leu Pro 1070 1075 1080 Gly Gln Gly Ala Phe Val Arg Ser Gln Thr Glu Thr Lys Val Glu 1085 1090 1095 Pro Phe Glu Val Pro Asn Pro Leu Pro Leu Ile Val Gly Ser Ser 1100 1105 1110 Val Gly Gly Leu Leu Leu Leu Ala Leu Ile Thr Ala Ala Leu Tyr 1115 1120 1125 Lys Leu Gly Phe Phe Lys Arg Gln Tyr Lys Asp Met Met Ser Glu 1130 1135 1140 Gly Gly Pro Pro Gly Ala Glu Pro Gln 1145 1150 <210> 46 <211> 1163 <212> PRT <213> Homo sapiens <400> 46 Met Thr Arg Thr Arg Ala Ala Leu Leu Leu Phe Thr Ala Leu Ala Thr 1 5 10 15 Ser Leu Gly Phe Asn Leu Asp Thr Glu Glu Leu Thr Ala Phe Arg Val 20 25 30 Asp Ser Ala Gly Phe Gly Asp Ser Val Val Gln Tyr Ala Asn Ser Trp 35 40 45 Val Val Val Gly Ala Pro Gln Lys Ile Thr Ala Ala Asn Gln Thr Gly 50 55 60 Gly Leu Tyr Gln Cys Gly Tyr Ser Thr Gly Ala Cys Glu Pro Ile Gly 65 70 75 80 Leu Gln Val Pro Pro Glu Ala Val Asn Met Ser Leu Gly Leu Ser Leu 85 90 95 Ala Ser Thr Thr Ser Pro Ser Gln Leu Leu Ala Cys Gly Pro Thr Val 100 105 110 His His Glu Cys Gly Arg Asn Met Tyr Leu Thr Gly Leu Cys Phe Leu 115 120 125 Leu Gly Pro Thr Gln Leu Thr Gln Arg Leu Pro Val Ser Arg Gln Glu 130 135 140 Cys Pro Arg Gln Glu Gln Asp Ile Val Phe Leu Ile Asp Gly Ser Gly 145 150 155 160 Ser Ile Ser Ser Arg Asn Phe Ala Thr Met Met Asn Phe Val Arg Ala 165 170 175 Val Ile Ser Gln Phe Gln Arg Pro Ser Thr Gln Phe Ser Leu Met Gln 180 185 190 Phe Ser Asn Lys Phe Gln Thr His Phe Thr Phe Glu Glu Phe Arg Arg 195 200 205 Ser Ser Asn Pro Leu Ser Leu Leu Ala Ser Val His Gln Leu Gln Gly 210 215 220 Phe Thr Tyr Thr Ala Thr Ala Ile Gln Asn Val Val His Arg Leu Phe 225 230 235 240 His Ala Ser Tyr Gly Ala Arg Arg Asp Ala Ala Lys Ile Leu Ile Val 245 250 255 Ile Thr Asp Gly Lys Lys Glu Gly Asp Ser Leu Asp Tyr Lys Asp Val 260 265 270 Ile Pro Met Ala Asp Ala Ala Gly Ile Ile Arg Tyr Ala Ile Gly Val 275 280 285 Gly Leu Ala Phe Gln Asn Arg Asn Ser Trp Lys Glu Leu Asn Asp Ile 290 295 300 Ala Ser Lys Pro Ser Gln Glu His Ile Phe Lys Val Glu Asp Phe Asp 305 310 315 320 Ala Leu Lys Asp Ile Gln Asn Gln Leu Lys Glu Lys Ile Phe Ala Ile 325 330 335 Glu Gly Thr Glu Thr Thr Ser Ser Ser Ser Phe Glu Leu Glu Met Ala 340 345 350 Gln Glu Gly Phe Ser Ala Val Phe Thr Pro Asp Gly Pro Val Leu Gly 355 360 365 Ala Val Gly Ser Phe Thr Trp Ser Gly Gly Ala Phe Leu Tyr Pro Pro 370 375 380 Asn Met Ser Pro Thr Phe Ile Asn Met Ser Gln Glu Asn Val Asp Met 385 390 395 400 Arg Asp Ser Tyr Leu Gly Tyr Ser Thr Glu Leu Ala Leu Trp Lys Gly 405 410 415 Val Gln Ser Leu Val Leu Gly Ala Pro Arg Tyr Gln His Thr Gly Lys 420 425 430 Ala Val Ile Phe Thr Gln Val Ser Arg Gln Trp Arg Met Lys Ala Glu 435 440 445 Val Thr Gly Thr Gln Ile Gly Ser Tyr Phe Gly Ala Ser Leu Cys Ser 450 455 460 Val Asp Val Asp Ser Asp Gly Ser Thr Asp Leu Val Leu Ile Gly Ala 465 470 475 480 Pro His Tyr Tyr Glu Gln Thr Arg Gly Gly Gln Val Ser Val Cys Pro 485 490 495 Leu Pro Arg Gly Trp Arg Arg Trp Trp Cys Asp Ala Val Leu Tyr Gly 500 505 510 Glu Gln Gly His Pro Trp Gly Arg Phe Gly Ala Ala Leu Thr Val Leu 515 520 525 Gly Asp Val Asn Gly Asp Lys Leu Thr Asp Val Val Ile Gly Ala Pro 530 535 540 Gly Glu Glu Glu Asn Arg Gly Ala Val Tyr Leu Phe His Gly Val Leu 545 550 555 560 Gly Pro Ser Ile Ser Pro Ser His Ser Gln Arg Ile Ala Gly Ser Gln 565 570 575 Leu Ser Ser Arg Leu Gln Tyr Phe Gly Gln Ala Leu Ser Gly Gly Gln 580 585 590 Asp Leu Thr Gln Asp Gly Leu Val Asp Leu Ala Val Gly Ala Arg Gly 595 600 605 Gln Val Leu Leu Leu Arg Thr Arg Pro Val Leu Trp Val Gly Val Ser 610 615 620 Met Gln Phe Ile Pro Ala Glu Ile Pro Arg Ser Ala Phe Glu Cys Arg 625 630 635 640 Glu Gln Val Val Ser Glu Gln Thr Leu Val Gln Ser Asn Ile Cys Leu 645 650 655 Tyr Ile Asp Lys Arg Ser Lys Asn Leu Leu Gly Ser Arg Asp Leu Gln 660 665 670 Ser Ser Val Thr Leu Asp Leu Ala Leu Asp Pro Gly Arg Leu Ser Pro 675 680 685 Arg Ala Thr Phe Gln Glu Thr Lys Asn Arg Ser Leu Ser Arg Val Arg 690 695 700 Val Leu Gly Leu Lys Ala His Cys Glu Asn Phe Asn Leu Leu Leu Pro 705 710 715 720 Ser Cys Val Glu Asp Ser Val Thr Pro Ile Thr Leu Arg Leu Asn Phe 725 730 735 Thr Leu Val Gly Lys Pro Leu Leu Ala Phe Arg Asn Leu Arg Pro Met 740 745 750 Leu Ala Ala Asp Ala Gln Arg Tyr Phe Thr Ala Ser Leu Pro Phe Glu 755 760 765 Lys Asn Cys Gly Ala Asp His Ile Cys Gln Asp Asn Leu Gly Ile Ser 770 775 780 Phe Ser Phe Pro Gly Leu Lys Ser Leu Leu Val Gly Ser Asn Leu Glu 785 790 795 800 Leu Asn Ala Glu Val Met Val Trp Asn Asp Gly Glu Asp Ser Tyr Gly 805 810 815 Thr Thr Ile Thr Phe Ser His Pro Ala Gly Leu Ser Tyr Arg Tyr Val 820 825 830 Ala Glu Gly Gln Lys Gln Gly Gln Leu Arg Ser Leu His Leu Thr Cys 835 840 845 Asp Ser Ala Pro Val Gly Ser Gln Gly Thr Trp Ser Thr Ser Cys Arg 850 855 860 Ile Asn His Leu Ile Phe Arg Gly Gly Ala Gln Ile Thr Phe Leu Ala 865 870 875 880 Thr Phe Asp Val Ser Pro Lys Ala Val Leu Gly Asp Arg Leu Leu Leu 885 890 895 Thr Ala Asn Val Ser Ser Glu Asn Asn Thr Pro Arg Thr Ser Lys Thr 900 905 910 Thr Phe Gln Leu Glu Leu Pro Val Lys Tyr Ala Val Tyr Thr Val Val 915 920 925 Ser Ser His Glu Gln Phe Thr Lys Tyr Leu Asn Phe Ser Glu Ser Glu 930 935 940 Glu Lys Glu Ser His Val Ala Met His Arg Tyr Gln Val Asn Asn Leu 945 950 955 960 Gly Gln Arg Asp Leu Pro Val Ser Ile Asn Phe Trp Val Pro Val Glu 965 970 975 Leu Asn Gln Glu Ala Val Trp Met Asp Val Glu Val Ser His Pro Gln 980 985 990 Asn Pro Ser Leu Arg Cys Ser Ser Glu Lys Ile Ala Pro Pro Ala Ser 995 1000 1005 Asp Phe Leu Ala His Ile Gln Lys Asn Pro Val Leu Asp Cys Ser 1010 1015 1020 Ile Ala Gly Cys Leu Arg Phe Arg Cys Asp Val Pro Ser Phe Ser 1025 1030 1035 Val Gln Glu Glu Leu Asp Phe Thr Leu Lys Gly Asn Leu Ser Phe 1040 1045 1050 Gly Trp Val Arg Gln Ile Leu Gln Lys Lys Val Ser Val Val Ser 1055 1060 1065 Val Ala Glu Ile Thr Phe Asp Thr Ser Val Tyr Ser Gln Leu Pro 1070 1075 1080 Gly Gln Glu Ala Phe Met Arg Ala Gln Thr Thr Thr Val Leu Glu 1085 1090 1095 Lys Tyr Lys Val His Asn Pro Thr Pro Leu Ile Val Gly Ser Ser 1100 1105 1110 Ile Gly Gly Leu Leu Leu Leu Ala Leu Ile Thr Ala Val Leu Tyr 1115 1120 1125 Lys Val Gly Phe Phe Lys Arg Gln Tyr Lys Glu Met Met Glu Glu 1130 1135 1140 Ala Asn Gly Gln Ile Ala Pro Glu Asn Gly Thr Gln Thr Pro Ser 1145 1150 1155 Pro Pro Ser Glu Lys 1160 <210> 47 <211> 375 <212> PRT <213> Homo sapiens <400> 47 Met Glu Arg Ala Ser Cys Leu Leu Leu Leu Leu Leu Pro Leu Val His 1 5 10 15 Val Ser Ala Thr Thr Pro Glu Pro Cys Glu Leu Asp Asp Glu Asp Phe 20 25 30 Arg Cys Val Cys Asn Phe Ser Glu Pro Gln Pro Asp Trp Ser Glu Ala 35 40 45 Phe Gln Cys Val Ser Ala Val Glu Val Glu Ile His Ala Gly Gly Leu 50 55 60 Asn Leu Glu Pro Phe Leu Lys Arg Val Asp Ala Asp Ala Asp Pro Arg 65 70 75 80 Gln Tyr Ala Asp Thr Val Lys Ala Leu Arg Val Arg Arg Leu Thr Val 85 90 95 Gly Ala Ala Gln Val Pro Ala Gln Leu Leu Val Gly Ala Leu Arg Val 100 105 110 Leu Ala Tyr Ser Arg Leu Lys Glu Leu Thr Leu Glu Asp Leu Lys Ile 115 120 125 Thr Gly Thr Met Pro Pro Leu Pro Leu Glu Ala Thr Gly Leu Ala Leu 130 135 140 Ser Ser Leu Arg Leu Arg Asn Val Ser Trp Ala Thr Gly Arg Ser Trp 145 150 155 160 Leu Ala Glu Leu Gln Gln Trp Leu Lys Pro Gly Leu Lys Val Leu Ser 165 170 175 Ile Ala Gln Ala His Ser Pro Ala Phe Ser Cys Glu Gln Val Arg Ala 180 185 190 Phe Pro Ala Leu Thr Ser Leu Asp Leu Ser Asp Asn Pro Gly Leu Gly 195 200 205 Glu Arg Gly Leu Met Ala Ala Leu Cys Pro His Lys Phe Pro Ala Ile 210 215 220 Gln Asn Leu Ala Leu Arg Asn Thr Gly Met Glu Thr Pro Thr Gly Val 225 230 235 240 Cys Ala Ala Leu Ala Ala Ala Gly Val Gln Pro His Ser Leu Asp Leu 245 250 255 Ser His Asn Ser Leu Arg Ala Thr Val Asn Pro Ser Ala Pro Arg Cys 260 265 270 Met Trp Ser Ser Ala Leu Asn Ser Leu Asn Leu Ser Phe Ala Gly Leu 275 280 285 Glu Gln Val Pro Lys Gly Leu Pro Ala Lys Leu Arg Val Leu Asp Leu 290 295 300 Ser Cys Asn Arg Leu Asn Arg Ala Pro Gln Pro Asp Glu Leu Pro Glu 305 310 315 320 Val Asp Asn Leu Thr Leu Asp Gly Asn Pro Phe Leu Val Pro Gly Thr 325 330 335 Ala Leu Pro His Glu Gly Ser Met Asn Ser Gly Val Val Pro Ala Cys 340 345 350 Ala Arg Ser Thr Leu Ser Val Gly Val Ser Gly Thr Leu Val Leu Leu 355 360 365 Gln Gly Ala Arg Gly Phe Ala 370 375 <210> 48 <211> 254 <212> PRT <213> Homo sapiens <400> 48 Met Trp Gln Leu Leu Leu Pro Thr Ala Leu Leu Leu Leu Val Ser Ala 1 5 10 15 Gly Met Arg Thr Glu Asp Leu Pro Lys Ala Val Val Phe Leu Glu Pro 20 25 30 Gln Trp Tyr Arg Val Leu Glu Lys Asp Ser Val Thr Leu Lys Cys Gln 35 40 45 Gly Ala Tyr Ser Pro Glu Asp Asn Ser Thr Gln Trp Phe His Asn Glu 50 55 60 Ser Leu Ile Ser Ser Gln Ala Ser Ser Tyr Phe Ile Asp Ala Ala Thr 65 70 75 80 Val Asp Asp Ser Gly Glu Tyr Arg Cys Gln Thr Asn Leu Ser Thr Leu 85 90 95 Ser Asp Pro Val Gln Leu Glu Val His Ile Gly Trp Leu Leu Leu Gln 100 105 110 Ala Pro Arg Trp Val Phe Lys Glu Glu Asp Pro Ile His Leu Arg Cys 115 120 125 His Ser Trp Lys Asn Thr Ala Leu His Lys Val Thr Tyr Leu Gln Asn 130 135 140 Gly Lys Gly Arg Lys Tyr Phe His His Asn Ser Asp Phe Tyr Ile Pro 145 150 155 160 Lys Ala Thr Leu Lys Asp Ser Gly Ser Tyr Phe Cys Arg Gly Leu Phe 165 170 175 Gly Ser Lys Asn Val Ser Ser Glu Thr Val Asn Ile Thr Ile Thr Gln 180 185 190 Gly Leu Ala Val Ser Thr Ile Ser Ser Phe Phe Pro Pro Gly Tyr Gln 195 200 205 Val Ser Phe Cys Leu Val Met Val Leu Leu Phe Ala Val Asp Thr Gly 210 215 220 Leu Tyr Phe Ser Val Lys Thr Asn Ile Arg Ser Ser Thr Arg Asp Trp 225 230 235 240 Lys Asp His Lys Phe Lys Trp Arg Lys Asp Pro Gln Asp Lys 245 250 <210> 49 <211> 510 <212> PRT <213> Homo sapiens <400> 49 Met Glu Asp Thr Lys Glu Ser Asn Val Lys Thr Phe Cys Ser Lys Asn 1 5 10 15 Ile Leu Ala Ile Leu Gly Phe Ser Ser Ile Ile Ala Val Ile Ala Leu 20 25 30 Leu Ala Val Gly Leu Thr Gln Asn Lys Ala Leu Pro Glu Asn Val Lys 35 40 45 Tyr Gly Ile Val Leu Asp Ala Gly Ser Ser His Thr Ser Leu Tyr Ile 50 55 60 Tyr Lys Trp Pro Ala Glu Lys Glu Asn Asp Thr Gly Val Val His Gln 65 70 75 80 Val Glu Glu Cys Arg Val Lys Gly Pro Gly Ile Ser Lys Phe Val Gln 85 90 95 Lys Val Asn Glu Ile Gly Ile Tyr Leu Thr Asp Cys Met Glu Arg Ala 100 105 110 Arg Glu Val Ile Pro Arg Ser Gln His Gln Glu Thr Pro Val Tyr Leu 115 120 125 Gly Ala Thr Ala Gly Met Arg Leu Leu Arg Met Glu Ser Glu Glu Leu 130 135 140 Ala Asp Arg Val Leu Asp Val Val Glu Arg Ser Leu Ser Asn Tyr Pro 145 150 155 160 Phe Asp Phe Gln Gly Ala Arg Ile Ile Thr Gly Gln Glu Glu Gly Ala 165 170 175 Tyr Gly Trp Ile Thr Ile Asn Tyr Leu Leu Gly Lys Phe Ser Gln Lys 180 185 190 Thr Arg Trp Phe Ser Ile Val Pro Tyr Glu Thr Asn Asn Gln Glu Thr 195 200 205 Phe Gly Ala Leu Asp Leu Gly Gly Ala Ser Thr Gln Val Thr Phe Val 210 215 220 Pro Gln Asn Gln Thr Ile Glu Ser Pro Asp Asn Ala Leu Gln Phe Arg 225 230 235 240 Leu Tyr Gly Lys Asp Tyr Asn Val Tyr Thr His Ser Phe Leu Cys Tyr 245 250 255 Gly Lys Asp Gln Ala Leu Trp Gln Lys Leu Ala Lys Asp Ile Gln Val 260 265 270 Ala Ser Asn Glu Ile Leu Arg Asp Pro Cys Phe His Pro Gly Tyr Lys 275 280 285 Lys Val Val Asn Val Ser Asp Leu Tyr Lys Thr Pro Cys Thr Lys Arg 290 295 300 Phe Glu Met Thr Leu Pro Phe Gln Gln Phe Glu Ile Gln Gly Ile Gly 305 310 315 320 Asn Tyr Gln Gln Cys His Gln Ser Ile Leu Glu Leu Phe Asn Thr Ser 325 330 335 Tyr Cys Pro Tyr Ser Gln Cys Ala Phe Asn Gly Ile Phe Leu Pro Pro 340 345 350 Leu Gln Gly Asp Phe Gly Ala Phe Ser Ala Phe Tyr Phe Val Met Lys 355 360 365 Phe Leu Asn Leu Thr Ser Glu Lys Val Ser Gln Glu Lys Val Thr Glu 370 375 380 Met Met Lys Lys Phe Cys Ala Gln Pro Trp Glu Glu Ile Lys Thr Ser 385 390 395 400 Tyr Ala Gly Val Lys Glu Lys Tyr Leu Ser Glu Tyr Cys Phe Ser Gly 405 410 415 Thr Tyr Ile Leu Ser Leu Leu Leu Gln Gly Tyr His Phe Thr Ala Asp 420 425 430 Ser Trp Glu His Ile His Phe Ile Gly Lys Ile Gln Gly Ser Asp Ala 435 440 445 Gly Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr Asn Met Ile Pro Ala 450 455 460 Glu Gln Pro Leu Ser Thr Pro Leu Ser His Ser Thr Tyr Val Phe Leu 465 470 475 480 Met Val Leu Phe Ser Leu Val Leu Phe Thr Val Ala Ile Ile Gly Leu 485 490 495 Leu Ile Phe His Lys Pro Ser Tyr Phe Trp Lys Asp Met Val 500 505 510 <210> 50 <211> 1306 <212> PRT <213> Homo sapiens <400> 50 Met Thr Met Tyr Leu Trp Leu Lys Leu Leu Ala Phe Gly Phe Ala Phe 1 5 10 15 Leu Asp Thr Glu Val Phe Val Thr Gly Gln Ser Pro Thr Pro Ser Pro 20 25 30 Thr Gly Leu Thr Thr Ala Lys Met Pro Ser Val Pro Leu Ser Ser Asp 35 40 45 Pro Leu Pro Thr His Thr Thr Ala Phe Ser Pro Ala Ser Thr Phe Glu 50 55 60 Arg Glu Asn Asp Phe Ser Glu Thr Thr Thr Ser Leu Ser Pro Asp Asn 65 70 75 80 Thr Ser Thr Gln Val Ser Pro Asp Ser Leu Asp Asn Ala Ser Ala Phe 85 90 95 Asn Thr Thr Gly Val Ser Ser Val Gln Thr Pro His Leu Pro Thr His 100 105 110 Ala Asp Ser Gln Thr Pro Ser Ala Gly Thr Asp Thr Gln Thr Phe Ser 115 120 125 Gly Ser Ala Ala Asn Ala Lys Leu Asn Pro Thr Pro Gly Ser Asn Ala 130 135 140 Ile Ser Asp Val Pro Gly Glu Arg Ser Thr Ala Ser Thr Phe Pro Thr 145 150 155 160 Asp Pro Val Ser Pro Leu Thr Thr Thr Leu Ser Leu Ala His His Ser 165 170 175 Ser Ala Ala Leu Pro Ala Arg Thr Ser Asn Thr Thr Ile Thr Ala Asn 180 185 190 Thr Ser Asp Ala Tyr Leu Asn Ala Ser Glu Thr Thr Thr Leu Ser Pro 195 200 205 Ser Gly Ser Ala Val Ile Ser Thr Thr Thr Ile Ala Thr Thr Pro Ser 210 215 220 Lys Pro Thr Cys Asp Glu Lys Tyr Ala Asn Ile Thr Val Asp Tyr Leu 225 230 235 240 Tyr Asn Lys Glu Thr Lys Leu Phe Thr Ala Lys Leu Asn Val Asn Glu 245 250 255 Asn Val Glu Cys Gly Asn Asn Thr Cys Thr Asn Asn Glu Val His Asn 260 265 270 Leu Thr Glu Cys Lys Asn Ala Ser Val Ser Ile Ser His Asn Ser Cys 275 280 285 Thr Ala Pro Asp Lys Thr Leu Ile Leu Asp Val Pro Pro Gly Val Glu 290 295 300 Lys Phe Gln Leu His Asp Cys Thr Gln Val Glu Lys Ala Asp Thr Thr 305 310 315 320 Ile Cys Leu Lys Trp Lys Asn Ile Glu Thr Phe Thr Cys Asp Thr Gln 325 330 335 Asn Ile Thr Tyr Arg Phe Gln Cys Gly Asn Met Ile Phe Asp Asn Lys 340 345 350 Glu Ile Lys Leu Glu Asn Leu Glu Pro Glu His Glu Tyr Lys Cys Asp 355 360 365 Ser Glu Ile Leu Tyr Asn Asn His Lys Phe Thr Asn Ala Ser Lys Ile 370 375 380 Ile Lys Thr Asp Phe Gly Ser Pro Gly Glu Pro Gln Ile Ile Phe Cys 385 390 395 400 Arg Ser Glu Ala Ala His Gln Gly Val Ile Thr Trp Asn Pro Pro Gln 405 410 415 Arg Ser Phe His Asn Phe Thr Leu Cys Tyr Ile Lys Glu Thr Glu Lys 420 425 430 Asp Cys Leu Asn Leu Asp Lys Asn Leu Ile Lys Tyr Asp Leu Gln Asn 435 440 445 Leu Lys Pro Tyr Thr Lys Tyr Val Leu Ser Leu His Ala Tyr Ile Ile 450 455 460 Ala Lys Val Gln Arg Asn Gly Ser Ala Ala Met Cys His Phe Thr Thr 465 470 475 480 Lys Ser Ala Pro Pro Ser Gln Val Trp Asn Met Thr Val Ser Met Thr 485 490 495 Ser Asp Asn Ser Met His Val Lys Cys Arg Pro Pro Arg Asp Arg Asn 500 505 510 Gly Pro His Glu Arg Tyr His Leu Glu Val Glu Ala Gly Asn Thr Leu 515 520 525 Val Arg Asn Glu Ser His Lys Asn Cys Asp Phe Arg Val Lys Asp Leu 530 535 540 Gln Tyr Ser Thr Asp Tyr Thr Phe Lys Ala Tyr Phe His Asn Gly Asp 545 550 555 560 Tyr Pro Gly Glu Pro Phe Ile Leu His His Ser Thr Ser Tyr Asn Ser 565 570 575 Lys Ala Leu Ile Ala Phe Leu Ala Phe Leu Ile Ile Val Thr Ser Ile 580 585 590 Ala Leu Leu Val Val Leu Tyr Lys Ile Tyr Asp Leu His Lys Lys Arg 595 600 605 Ser Cys Asn Leu Asp Glu Gln Gln Glu Leu Val Glu Arg Asp Asp Glu 610 615 620 Lys Gln Leu Met Asn Val Glu Pro Ile His Ala Asp Ile Leu Leu Glu 625 630 635 640 Thr Tyr Lys Arg Lys Ile Ala Asp Glu Gly Arg Leu Phe Leu Ala Glu 645 650 655 Phe Gln Ser Ile Pro Arg Val Phe Ser Lys Phe Pro Ile Lys Glu Ala 660 665 670 Arg Lys Pro Phe Asn Gln Asn Lys Asn Arg Tyr Val Asp Ile Leu Pro 675 680 685 Tyr Asp Tyr Asn Arg Val Glu Leu Ser Glu Ile Asn Gly Asp Ala Gly 690 695 700 Ser Asn Tyr Ile Asn Ala Ser Tyr Ile Asp Gly Phe Lys Glu Pro Arg 705 710 715 720 Lys Tyr Ile Ala Ala Gln Gly Pro Arg Asp Glu Thr Val Asp Asp Phe 725 730 735 Trp Arg Met Ile Trp Glu Gln Lys Ala Thr Val Ile Val Met Val Thr 740 745 750 Arg Cys Glu Glu Gly Asn Arg Asn Lys Cys Ala Glu Tyr Trp Pro Ser 755 760 765 Met Glu Glu Gly Thr Arg Ala Phe Gly Asp Val Val Val Lys Ile Asn 770 775 780 Gln His Lys Arg Cys Pro Asp Tyr Ile Ile Gln Lys Leu Asn Ile Val 785 790 795 800 Asn Lys Lys Glu Lys Ala Thr Gly Arg Glu Val Thr His Ile Gln Phe 805 810 815 Thr Ser Trp Pro Asp His Gly Val Pro Glu Asp Pro His Leu Leu Leu 820 825 830 Lys Leu Arg Arg Arg Val Asn Ala Phe Ser Asn Phe Phe Ser Gly Pro 835 840 845 Ile Val Val His Cys Ser Ala Gly Val Gly Arg Thr Gly Thr Tyr Ile 850 855 860 Gly Ile Asp Ala Met Leu Glu Gly Leu Glu Ala Glu Asn Lys Val Asp 865 870 875 880 Val Tyr Gly Tyr Val Val Lys Leu Arg Arg Gln Arg Cys Leu Met Val 885 890 895 Gln Val Glu Ala Gln Tyr Ile Leu Ile His Gln Ala Leu Val Glu Tyr 900 905 910 Asn Gln Phe Gly Glu Thr Glu Val Asn Leu Ser Glu Leu His Pro Tyr 915 920 925 Leu His Asn Met Lys Lys Arg Asp Pro Pro Ser Glu Pro Ser Pro Leu 930 935 940 Glu Ala Glu Phe Gln Arg Leu Pro Ser Tyr Arg Ser Trp Arg Thr Gln 945 950 955 960 His Ile Gly Asn Gln Glu Glu Asn Lys Ser Lys Asn Arg Asn Ser Asn 965 970 975 Val Ile Pro Tyr Asp Tyr Asn Arg Val Pro Leu Lys His Glu Leu Glu 980 985 990 Met Ser Lys Glu Ser Glu His Asp Ser Asp Glu Ser Ser Asp Asp Asp 995 1000 1005 Ser Asp Ser Glu Glu Pro Ser Lys Tyr Ile Asn Ala Ser Phe Ile 1010 1015 1020 Met Ser Tyr Trp Lys Pro Glu Val Met Ile Ala Ala Gln Gly Pro 1025 1030 1035 Leu Lys Glu Thr Ile Gly Asp Phe Trp Gln Met Ile Phe Gln Arg 1040 1045 1050 Lys Val Lys Val Ile Val Met Leu Thr Glu Leu Lys His Gly Asp 1055 1060 1065 Gln Glu Ile Cys Ala Gln Tyr Trp Gly Glu Gly Lys Gln Thr Tyr 1070 1075 1080 Gly Asp Ile Glu Val Asp Leu Lys Asp Thr Asp Lys Ser Ser Thr 1085 1090 1095 Tyr Thr Leu Arg Val Phe Glu Leu Arg His Ser Lys Arg Lys Asp 1100 1105 1110 Ser Arg Thr Val Tyr Gln Tyr Gln Tyr Thr Asn Trp Ser Val Glu 1115 1120 1125 Gln Leu Pro Ala Glu Pro Lys Glu Leu Ile Ser Met Ile Gln Val 1130 1135 1140 Val Lys Gln Lys Leu Pro Gln Lys Asn Ser Ser Glu Gly Asn Lys 1145 1150 1155 His His Lys Ser Thr Pro Leu Leu Ile His Cys Arg Asp Gly Ser 1160 1165 1170 Gln Gln Thr Gly Ile Phe Cys Ala Leu Leu Asn Leu Leu Glu Ser 1175 1180 1185 Ala Glu Thr Glu Glu Val Val Asp Ile Phe Gln Val Val Lys Ala 1190 1195 1200 Leu Arg Lys Ala Arg Pro Gly Met Val Ser Thr Phe Glu Gln Tyr 1205 1210 1215 Gln Phe Leu Tyr Asp Val Ile Ala Ser Thr Tyr Pro Ala Gln Asn 1220 1225 1230 Gly Gln Val Lys Lys Asn Asn His Gln Glu Asp Lys Ile Glu Phe 1235 1240 1245 Asp Asn Glu Val Asp Lys Val Lys Gln Asp Ala Asn Cys Val Asn 1250 1255 1260 Pro Leu Gly Ala Pro Glu Lys Leu Pro Glu Ala Lys Glu Gln Ala 1265 1270 1275 Glu Gly Ser Glu Pro Thr Ser Gly Thr Glu Gly Pro Glu His Ser 1280 1285 1290 Val Asn Gly Pro Ala Ser Pro Ala Leu Asn Gln Gly Ser 1295 1300 1305 <210> 51 <211> 354 <212> PRT <213> Homo sapiens <400> 51 Met Arg Leu Ala Val Leu Phe Ser Gly Ala Leu Leu Gly Leu Leu Ala 1 5 10 15 Ala Gln Gly Thr Gly Asn Asp Cys Pro His Lys Lys Ser Ala Thr Leu 20 25 30 Leu Pro Ser Phe Thr Val Thr Pro Thr Val Thr Glu Ser Thr Gly Thr 35 40 45 Thr Ser His Arg Thr Thr Lys Ser His Lys Thr Thr Thr His Arg Thr 50 55 60 Thr Thr Thr Gly Thr Thr Ser His Gly Pro Thr Thr Ala Thr His Asn 65 70 75 80 Pro Thr Thr Thr Ser His Gly Asn Val Thr Val His Pro Thr Ser Asn 85 90 95 Ser Thr Ala Thr Ser Gln Gly Pro Ser Thr Ala Thr His Ser Pro Ala 100 105 110 Thr Thr Ser His Gly Asn Ala Thr Val His Pro Thr Ser Asn Ser Thr 115 120 125 Ala Thr Ser Pro Gly Phe Thr Ser Ser Ala His Pro Glu Pro Pro Pro 130 135 140 Pro Ser Pro Ser Pro Ser Pro Thr Ser Lys Glu Thr Ile Gly Asp Tyr 145 150 155 160 Thr Trp Thr Asn Gly Ser Gln Pro Cys Val His Leu Gln Ala Gln Ile 165 170 175 Gln Ile Arg Val Met Tyr Thr Thr Gln Gly Gly Gly Glu Ala Trp Gly 180 185 190 Ile Ser Val Leu Asn Pro Asn Lys Thr Lys Val Gln Gly Ser Cys Glu 195 200 205 Gly Ala His Pro His Leu Leu Leu Ser Phe Pro Tyr Gly His Leu Ser 210 215 220 Phe Gly Phe Met Gln Asp Leu Gln Gln Lys Val Val Tyr Leu Ser Tyr 225 230 235 240 Met Ala Val Glu Tyr Asn Val Ser Phe Pro His Ala Ala Gln Trp Thr 245 250 255 Phe Ser Ala Gln Asn Ala Ser Leu Arg Asp Leu Gln Ala Pro Leu Gly 260 265 270 Gln Ser Phe Ser Cys Ser Asn Ser Ser Ile Ile Leu Ser Pro Ala Val 275 280 285 His Leu Asp Leu Leu Ser Leu Arg Leu Gln Ala Ala Gln Leu Pro His 290 295 300 Thr Gly Val Phe Gly Gln Ser Phe Ser Cys Pro Ser Asp Arg Ser Ile 305 310 315 320 Leu Leu Pro Leu Ile Ile Gly Leu Ile Leu Leu Gly Leu Leu Ala Leu 325 330 335 Val Leu Ile Ala Phe Cys Ile Ile Arg Arg Arg Pro Ser Ala Tyr Gln 340 345 350 Ala Leu <210> 52 <211> 972 <212> PRT <213> Homo sapiens <400> 52 Met Gly Pro Gly Val Leu Leu Leu Leu Leu Val Ala Thr Ala Trp His 1 5 10 15 Gly Gln Gly Ile Pro Val Ile Glu Pro Ser Val Pro Glu Leu Val Val 20 25 30 Lys Pro Gly Ala Thr Val Thr Leu Arg Cys Val Gly Asn Gly Ser Val 35 40 45 Glu Trp Asp Gly Pro Pro Ser Pro His Trp Thr Leu Tyr Ser Asp Gly 50 55 60 Ser Ser Ser Ile Leu Ser Thr Asn Asn Ala Thr Phe Gln Asn Thr Gly 65 70 75 80 Thr Tyr Arg Cys Thr Glu Pro Gly Asp Pro Leu Gly Gly Ser Ala Ala 85 90 95 Ile His Leu Tyr Val Lys Asp Pro Ala Arg Pro Trp Asn Val Leu Ala 100 105 110 Gln Glu Val Val Val Phe Glu Asp Gln Asp Ala Leu Leu Pro Cys Leu 115 120 125 Leu Thr Asp Pro Val Leu Glu Ala Gly Val Ser Leu Val Arg Val Arg 130 135 140 Gly Arg Pro Leu Met Arg His Thr Asn Tyr Ser Phe Ser Pro Trp His 145 150 155 160 Gly Phe Thr Ile His Arg Ala Lys Phe Ile Gln Ser Gln Asp Tyr Gln 165 170 175 Cys Ser Ala Leu Met Gly Gly Arg Lys Val Met Ser Ile Ser Ile Arg 180 185 190 Leu Lys Val Gln Lys Val Ile Pro Gly Pro Pro Ala Leu Thr Leu Val 195 200 205 Pro Ala Glu Leu Val Arg Ile Arg Gly Glu Ala Ala Gln Ile Val Cys 210 215 220 Ser Ala Ser Ser Val Asp Val Asn Phe Asp Val Phe Leu Gln His Asn 225 230 235 240 Asn Thr Lys Leu Ala Ile Pro Gln Gln Ser Asp Phe His Asn Asn Arg 245 250 255 Tyr Gln Lys Val Leu Thr Leu Asn Leu Asp Gln Val Asp Phe Gln His 260 265 270 Ala Gly Asn Tyr Ser Cys Val Ala Ser Asn Val Gln Gly Lys His Ser 275 280 285 Thr Ser Met Phe Phe Arg Val Val Glu Ser Ala Tyr Leu Asn Leu Ser 290 295 300 Ser Glu Gln Asn Leu Ile Gln Glu Val Thr Val Gly Glu Gly Leu Asn 305 310 315 320 Leu Lys Val Met Val Glu Ala Tyr Pro Gly Leu Gln Gly Phe Asn Trp 325 330 335 Thr Tyr Leu Gly Pro Phe Ser Asp His Gln Pro Glu Pro Lys Leu Ala 340 345 350 Asn Ala Thr Thr Lys Asp Thr Tyr Arg His Thr Phe Thr Leu Ser Leu 355 360 365 Pro Arg Leu Lys Pro Ser Glu Ala Gly Arg Tyr Ser Phe Leu Ala Arg 370 375 380 Asn Pro Gly Gly Trp Arg Ala Leu Thr Phe Glu Leu Thr Leu Arg Tyr 385 390 395 400 Pro Pro Glu Val Ser Val Ile Trp Thr Phe Ile Asn Gly Ser Gly Thr 405 410 415 Leu Leu Cys Ala Ala Ser Gly Tyr Pro Gln Pro Asn Val Thr Trp Leu 420 425 430 Gln Cys Ser Gly His Thr Asp Arg Cys Asp Glu Ala Gln Val Leu Gln 435 440 445 Val Trp Asp Asp Pro Tyr Pro Glu Val Leu Ser Gln Glu Pro Phe His 450 455 460 Lys Val Thr Val Gln Ser Leu Leu Thr Val Glu Thr Leu Glu His Asn 465 470 475 480 Gln Thr Tyr Glu Cys Arg Ala His Asn Ser Val Gly Ser Gly Ser Trp 485 490 495 Ala Phe Ile Pro Ile Ser Ala Gly Ala His Thr His Pro Pro Asp Glu 500 505 510 Phe Leu Phe Thr Pro Val Val Val Ala Cys Met Ser Ile Met Ala Leu 515 520 525 Leu Leu Leu Leu Leu Leu Leu Leu Leu Tyr Lys Tyr Lys Gln Lys Pro 530 535 540 Lys Tyr Gln Val Arg Trp Lys Ile Ile Glu Ser Tyr Glu Gly Asn Ser 545 550 555 560 Tyr Thr Phe Ile Asp Pro Thr Gln Leu Pro Tyr Asn Glu Lys Trp Glu 565 570 575 Phe Pro Arg Asn Asn Leu Gln Phe Gly Lys Thr Leu Gly Ala Gly Ala 580 585 590 Phe Gly Lys Val Val Glu Ala Thr Ala Phe Gly Leu Gly Lys Glu Asp 595 600 605 Ala Val Leu Lys Val Ala Val Lys Met Leu Lys Ser Thr Ala His Ala 610 615 620 Asp Glu Lys Glu Ala Leu Met Ser Glu Leu Lys Ile Met Ser His Leu 625 630 635 640 Gly Gln His Glu Asn Ile Val Asn Leu Leu Gly Ala Cys Thr His Gly 645 650 655 Gly Pro Val Leu Val Ile Thr Glu Tyr Cys Cys Tyr Gly Asp Leu Leu 660 665 670 Asn Phe Leu Arg Arg Lys Ala Glu Ala Met Leu Gly Pro Ser Leu Ser 675 680 685 Pro Gly Gln Asp Pro Glu Gly Gly Val Asp Tyr Lys Asn Ile His Leu 690 695 700 Glu Lys Lys Tyr Val Arg Arg Asp Ser Gly Phe Ser Ser Gln Gly Val 705 710 715 720 Asp Thr Tyr Val Glu Met Arg Pro Val Ser Thr Ser Ser Asn Asp Ser 725 730 735 Phe Ser Glu Gln Asp Leu Asp Lys Glu Asp Gly Arg Pro Leu Glu Leu 740 745 750 Arg Asp Leu Leu His Phe Ser Ser Gln Val Ala Gln Gly Met Ala Phe 755 760 765 Leu Ala Ser Lys Asn Cys Ile His Arg Asp Val Ala Ala Arg Asn Val 770 775 780 Leu Leu Thr Asn Gly His Val Ala Lys Ile Gly Asp Phe Gly Leu Ala 785 790 795 800 Arg Asp Ile Met Asn Asp Ser Asn Tyr Ile Val Lys Gly Asn Ala Arg 805 810 815 Leu Pro Val Lys Trp Met Ala Pro Glu Ser Ile Phe Asp Cys Val Tyr 820 825 830 Thr Val Gln Ser Asp Val Trp Ser Tyr Gly Ile Leu Leu Trp Glu Ile 835 840 845 Phe Ser Leu Gly Leu Asn Pro Tyr Pro Gly Ile Leu Val Asn Ser Lys 850 855 860 Phe Tyr Lys Leu Val Lys Asp Gly Tyr Gln Met Ala Gln Pro Ala Phe 865 870 875 880 Ala Pro Lys Asn Ile Tyr Ser Ile Met Gln Ala Cys Trp Ala Leu Glu 885 890 895 Pro Thr His Arg Pro Thr Phe Gln Gln Ile Cys Ser Phe Leu Gln Glu 900 905 910 Gln Ala Gln Glu Asp Arg Arg Glu Arg Asp Tyr Thr Asn Leu Pro Ser 915 920 925 Ser Ser Arg Ser Gly Gly Ser Gly Ser Ser Ser Ser Glu Leu Glu Glu 930 935 940 Glu Ser Ser Ser Glu His Leu Thr Cys Cys Glu Gln Gly Asp Ile Ala 945 950 955 960 Gln Pro Leu Leu Gln Pro Asn Asn Tyr Gln Phe Cys 965 970 <210> 53 <211> 1156 <212> PRT <213> Homo sapiens <400> 53 Met Ser Lys Leu Arg Met Val Leu Leu Glu Asp Ser Gly Ser Ala Asp 1 5 10 15 Phe Arg Arg His Phe Val Asn Leu Ser Pro Phe Thr Ile Thr Val Val 20 25 30 Leu Leu Leu Ser Ala Cys Phe Val Thr Ser Ser Leu Gly Gly Thr Asp 35 40 45 Lys Glu Leu Arg Leu Val Asp Gly Glu Asn Lys Cys Ser Gly Arg Val 50 55 60 Glu Val Lys Val Gln Glu Glu Trp Gly Thr Val Cys Asn Asn Gly Trp 65 70 75 80 Ser Met Glu Ala Val Ser Val Ile Cys Asn Gln Leu Gly Cys Pro Thr 85 90 95 Ala Ile Lys Ala Pro Gly Trp Ala Asn Ser Ser Ala Gly Ser Gly Arg 100 105 110 Ile Trp Met Asp His Val Ser Cys Arg Gly Asn Glu Ser Ala Leu Trp 115 120 125 Asp Cys Lys His Asp Gly Trp Gly Lys His Ser Asn Cys Thr His Gln 130 135 140 Gln Asp Ala Gly Val Thr Cys Ser Asp Gly Ser Asn Leu Glu Met Arg 145 150 155 160 Leu Thr Arg Gly Gly Asn Met Cys Ser Gly Arg Ile Glu Ile Lys Phe 165 170 175 Gln Gly Arg Trp Gly Thr Val Cys Asp Asp Asn Phe Asn Ile Asp His 180 185 190 Ala Ser Val Ile Cys Arg Gln Leu Glu Cys Gly Ser Ala Val Ser Phe 195 200 205 Ser Gly Ser Ser Asn Phe Gly Glu Gly Ser Gly Pro Ile Trp Phe Asp 210 215 220 Asp Leu Ile Cys Asn Gly Asn Glu Ser Ala Leu Trp Asn Cys Lys His 225 230 235 240 Gln Gly Trp Gly Lys His Asn Cys Asp His Ala Glu Asp Ala Gly Val 245 250 255 Ile Cys Ser Lys Gly Ala Asp Leu Ser Leu Arg Leu Val Asp Gly Val 260 265 270 Thr Glu Cys Ser Gly Arg Leu Glu Val Arg Phe Gln Gly Glu Trp Gly 275 280 285 Thr Ile Cys Asp Asp Gly Trp Asp Ser Tyr Asp Ala Ala Val Ala Cys 290 295 300 Lys Gln Leu Gly Cys Pro Thr Ala Val Thr Ala Ile Gly Arg Val Asn 305 310 315 320 Ala Ser Lys Gly Phe Gly His Ile Trp Leu Asp Ser Val Ser Cys Gln 325 330 335 Gly His Glu Pro Ala Ile Trp Gln Cys Lys His His Glu Trp Gly Lys 340 345 350 His Tyr Cys Asn His Asn Glu Asp Ala Gly Val Thr Cys Ser Asp Gly 355 360 365 Ser Asp Leu Glu Leu Arg Leu Arg Gly Gly Gly Ser Arg Cys Ala Gly 370 375 380 Thr Val Glu Val Glu Ile Gln Arg Leu Leu Gly Lys Val Cys Asp Arg 385 390 395 400 Gly Trp Gly Leu Lys Glu Ala Asp Val Val Cys Arg Gln Leu Gly Cys 405 410 415 Gly Ser Ala Leu Lys Thr Ser Tyr Gln Val Tyr Ser Lys Ile Gln Ala 420 425 430 Thr Asn Thr Trp Leu Phe Leu Ser Ser Cys Asn Gly Asn Glu Thr Ser 435 440 445 Leu Trp Asp Cys Lys Asn Trp Gln Trp Gly Gly Leu Thr Cys Asp His 450 455 460 Tyr Glu Glu Ala Lys Ile Thr Cys Ser Ala His Arg Glu Pro Arg Leu 465 470 475 480 Val Gly Gly Asp Ile Pro Cys Ser Gly Arg Val Glu Val Lys His Gly 485 490 495 Asp Thr Trp Gly Ser Ile Cys Asp Ser Asp Phe Ser Leu Glu Ala Ala 500 505 510 Ser Val Leu Cys Arg Glu Leu Gln Cys Gly Thr Val Val Ser Ile Leu 515 520 525 Gly Gly Ala His Phe Gly Glu Gly Asn Gly Gln Ile Trp Ala Glu Glu 530 535 540 Phe Gln Cys Glu Gly His Glu Ser His Leu Ser Leu Cys Pro Val Ala 545 550 555 560 Pro Arg Pro Glu Gly Thr Cys Ser His Ser Arg Asp Val Gly Val Val 565 570 575 Cys Ser Arg Tyr Thr Glu Ile Arg Leu Val Asn Gly Lys Thr Pro Cys 580 585 590 Glu Gly Arg Val Glu Leu Lys Thr Leu Gly Ala Trp Gly Ser Leu Cys 595 600 605 Asn Ser His Trp Asp Ile Glu Asp Ala His Val Leu Cys Gln Gln Leu 610 615 620 Lys Cys Gly Val Ala Leu Ser Thr Pro Gly Gly Ala Arg Phe Gly Lys 625 630 635 640 Gly Asn Gly Gln Ile Trp Arg His Met Phe His Cys Thr Gly Thr Glu 645 650 655 Gln His Met Gly Asp Cys Pro Val Thr Ala Leu Gly Ala Ser Leu Cys 660 665 670 Pro Ser Glu Gln Val Ala Ser Val Ile Cys Ser Gly Asn Gln Ser Gln 675 680 685 Thr Leu Ser Ser Cys Asn Ser Ser Ser Leu Gly Pro Thr Arg Pro Thr 690 695 700 Ile Pro Glu Glu Ser Ala Val Ala Cys Ile Glu Ser Gly Gln Leu Arg 705 710 715 720 Leu Val Asn Gly Gly Gly Arg Cys Ala Gly Arg Val Glu Ile Tyr His 725 730 735 Glu Gly Ser Trp Gly Thr Ile Cys Asp Asp Ser Trp Asp Leu Ser Asp 740 745 750 Ala His Val Val Cys Arg Gln Leu Gly Cys Gly Glu Ala Ile Asn Ala 755 760 765 Thr Gly Ser Ala His Phe Gly Glu Gly Thr Gly Pro Ile Trp Leu Asp 770 775 780 Glu Met Lys Cys Asn Gly Lys Glu Ser Arg Ile Trp Gln Cys His Ser 785 790 795 800 His Gly Trp Gly Gln Gln Asn Cys Arg His Lys Glu Asp Ala Gly Val 805 810 815 Ile Cys Ser Glu Phe Met Ser Leu Arg Leu Thr Ser Glu Ala Ser Arg 820 825 830 Glu Ala Cys Ala Gly Arg Leu Glu Val Phe Tyr Asn Gly Ala Trp Gly 835 840 845 Thr Val Gly Lys Ser Ser Met Ser Glu Thr Thr Val Gly Val Val Cys 850 855 860 Arg Gln Leu Gly Cys Ala Asp Lys Gly Lys Ile Asn Pro Ala Ser Leu 865 870 875 880 Asp Lys Ala Met Ser Ile Pro Met Trp Val Asp Asn Val Gln Cys Pro 885 890 895 Lys Gly Pro Asp Thr Leu Trp Gln Cys Pro Ser Ser Pro Trp Glu Lys 900 905 910 Arg Leu Ala Ser Pro Ser Glu Glu Thr Trp Ile Thr Cys Asp Asn Lys 915 920 925 Ile Arg Leu Gln Glu Gly Pro Thr Ser Cys Ser Gly Arg Val Glu Ile 930 935 940 Trp His Gly Gly Ser Trp Gly Thr Val Cys Asp Asp Ser Trp Asp Leu 945 950 955 960 Asp Asp Ala Gln Val Val Cys Gln Gln Leu Gly Cys Gly Pro Ala Leu 965 970 975 Lys Ala Phe Lys Glu Ala Glu Phe Gly Gln Gly Thr Gly Pro Ile Trp 980 985 990 Leu Asn Glu Val Lys Cys Lys Gly Asn Glu Ser Ser Leu Trp Asp Cys 995 1000 1005 Pro Ala Arg Arg Trp Gly His Ser Glu Cys Gly His Lys Glu Asp 1010 1015 1020 Ala Ala Val Asn Cys Thr Asp Ile Ser Val Gln Lys Thr Pro Gln 1025 1030 1035 Lys Ala Thr Thr Gly Arg Ser Ser Arg Gln Ser Ser Phe Ile Ala 1040 1045 1050 Val Gly Ile Leu Gly Val Val Leu Leu Ala Ile Phe Val Ala Leu 1055 1060 1065 Phe Phe Leu Thr Lys Lys Arg Arg Gln Arg Gln Arg Leu Ala Val 1070 1075 1080 Ser Ser Arg Gly Glu Asn Leu Val His Gln Ile Gln Tyr Arg Glu 1085 1090 1095 Met Asn Ser Cys Leu Asn Ala Asp Asp Leu Asp Leu Met Asn Ser 1100 1105 1110 Ser Glu Asn Ser His Glu Ser Ala Asp Phe Ser Ala Ala Glu Leu 1115 1120 1125 Ile Ser Val Ser Lys Phe Leu Pro Ile Ser Gly Met Glu Lys Glu 1130 1135 1140 Ala Ile Leu Ser His Thr Glu Lys Glu Asn Gly Asn Leu 1145 1150 1155 <210> 54 <211> 355 <212> PRT <213> Homo sapiens <400> 54 Met Asp Gln Phe Pro Glu Ser Val Thr Glu Asn Phe Glu Tyr Asp Asp 1 5 10 15 Leu Ala Glu Ala Cys Tyr Ile Gly Asp Ile Val Val Phe Gly Thr Val 20 25 30 Phe Leu Ser Ile Phe Tyr Ser Val Ile Phe Ala Ile Gly Leu Val Gly 35 40 45 Asn Leu Leu Val Val Phe Ala Leu Thr Asn Ser Lys Lys Pro Lys Ser 50 55 60 Val Thr Asp Ile Tyr Leu Leu Asn Leu Ala Leu Ser Asp Leu Leu Phe 65 70 75 80 Val Ala Thr Leu Pro Phe Trp Thr His Tyr Leu Ile Asn Glu Lys Gly 85 90 95 Leu His Asn Ala Met Cys Lys Phe Thr Thr Ala Phe Phe Phe Ile Gly 100 105 110 Phe Phe Gly Ser Ile Phe Phe Ile Thr Val Ile Ser Ile Asp Arg Tyr 115 120 125 Leu Ala Ile Val Leu Ala Ala Asn Ser Met Asn Asn Arg Thr Val Gln 130 135 140 His Gly Val Thr Ile Ser Leu Gly Val Trp Ala Ala Ala Ile Leu Val 145 150 155 160 Ala Ala Pro Gln Phe Met Phe Thr Lys Gln Lys Glu Asn Glu Cys Leu 165 170 175 Gly Asp Tyr Pro Glu Val Leu Gln Glu Ile Trp Pro Val Leu Arg Asn 180 185 190 Val Glu Thr Asn Phe Leu Gly Phe Leu Leu Pro Leu Leu Ile Met Ser 195 200 205 Tyr Cys Tyr Phe Arg Ile Ile Gln Thr Leu Phe Ser Cys Lys Asn His 210 215 220 Lys Lys Ala Lys Ala Ile Lys Leu Ile Leu Leu Val Val Ile Val Phe 225 230 235 240 Phe Leu Phe Trp Thr Pro Tyr Asn Val Met Ile Phe Leu Glu Thr Leu 245 250 255 Lys Leu Tyr Asp Phe Phe Pro Ser Cys Asp Met Arg Lys Asp Leu Arg 260 265 270 Leu Ala Leu Ser Val Thr Glu Thr Val Ala Phe Ser His Cys Cys Leu 275 280 285 Asn Pro Leu Ile Tyr Ala Phe Ala Gly Glu Lys Phe Arg Arg Tyr Leu 290 295 300 Tyr His Leu Tyr Gly Lys Cys Leu Ala Val Leu Cys Gly Arg Ser Val 305 310 315 320 His Val Asp Phe Ser Ser Ser Glu Ser Gln Arg Ser Arg His Gly Ser 325 330 335 Val Leu Ser Ser Asn Phe Thr Tyr His Thr Ser Asp Gly Asp Ala Leu 340 345 350 Leu Leu Leu 355 <210> 55 <211> 230 <212> PRT <213> Homo sapiens <400> 55 Met Glu Pro Leu Arg Leu Leu Ile Leu Leu Phe Val Thr Glu Leu Ser 1 5 10 15 Gly Ala His Asn Thr Thr Val Phe Gln Gly Val Ala Gly Gln Ser Leu 20 25 30 Gln Val Ser Cys Pro Tyr Asp Ser Met Lys His Trp Gly Arg Arg Lys 35 40 45 Ala Trp Cys Arg Gln Leu Gly Glu Lys Gly Pro Cys Gln Arg Val Val 50 55 60 Ser Thr His Asn Leu Trp Leu Leu Ser Phe Leu Arg Arg Trp Asn Gly 65 70 75 80 Ser Thr Ala Ile Thr Asp Asp Thr Leu Gly Gly Thr Leu Thr Ile Thr 85 90 95 Leu Arg Asn Leu Gln Pro His Asp Ala Gly Leu Tyr Gln Cys Gln Ser 100 105 110 Leu His Gly Ser Glu Ala Asp Thr Leu Arg Lys Val Leu Val Glu Val 115 120 125 Leu Ala Asp Pro Leu Asp His Arg Asp Ala Gly Asp Leu Trp Phe Pro 130 135 140 Gly Glu Ser Glu Ser Phe Glu Asp Ala His Val Glu His Ser Ile Ser 145 150 155 160 Arg Ser Leu Leu Glu Gly Glu Ile Pro Phe Pro Pro Thr Ser Ile Leu 165 170 175 Leu Leu Leu Ala Cys Ile Phe Leu Ile Lys Ile Leu Ala Ala Ser Ala 180 185 190 Leu Trp Ala Ala Ala Trp His Gly Gln Lys Pro Gly Thr His Pro Pro 195 200 205 Ser Glu Leu Asp Cys Gly His Asp Pro Gly Tyr Gln Leu Gln Thr Leu 210 215 220 Pro Gly Leu Arg Asp Thr 225 230 <210> 56 <211> 342 <212> PRT <213> Homo sapiens <400> 56 Met Gln Ala Val Asp Asn Leu Thr Ser Ala Pro Gly Asn Thr Ser Leu 1 5 10 15 Cys Thr Arg Asp Tyr Lys Ile Thr Gln Val Leu Phe Pro Leu Leu Tyr 20 25 30 Thr Val Leu Phe Phe Val Gly Leu Ile Thr Asn Gly Leu Ala Met Arg 35 40 45 Ile Phe Phe Gln Ile Arg Ser Lys Ser Asn Phe Ile Ile Phe Leu Lys 50 55 60 Asn Thr Val Ile Ser Asp Leu Leu Met Ile Leu Thr Phe Pro Phe Lys 65 70 75 80 Ile Leu Ser Asp Ala Lys Leu Gly Thr Gly Pro Leu Arg Thr Phe Val 85 90 95 Cys Gln Val Thr Ser Val Ile Phe Tyr Phe Thr Met Tyr Ile Ser Ile 100 105 110 Ser Phe Leu Gly Leu Ile Thr Ile Asp Arg Tyr Gln Lys Thr Thr Arg 115 120 125 Pro Phe Lys Thr Ser Asn Pro Lys Asn Leu Leu Gly Ala Lys Ile Leu 130 135 140 Ser Val Val Ile Trp Ala Phe Met Phe Leu Leu Ser Leu Pro Asn Met 145 150 155 160 Ile Leu Thr Asn Arg Gln Pro Arg Asp Lys Asn Val Lys Lys Cys Ser 165 170 175 Phe Leu Lys Ser Glu Phe Gly Leu Val Trp His Glu Ile Val Asn Tyr 180 185 190 Ile Cys Gln Val Ile Phe Trp Ile Asn Phe Leu Ile Val Ile Val Cys 195 200 205 Tyr Thr Leu Ile Thr Lys Glu Leu Tyr Arg Ser Tyr Val Arg Thr Arg 210 215 220 Gly Val Gly Lys Val Pro Arg Lys Lys Val Asn Val Lys Val Phe Ile 225 230 235 240 Ile Ile Ala Val Phe Phe Ile Cys Phe Val Pro Phe His Phe Ala Arg 245 250 255 Ile Pro Tyr Thr Leu Ser Gln Thr Arg Asp Val Phe Asp Cys Thr Ala 260 265 270 Glu Asn Thr Leu Phe Tyr Val Lys Glu Ser Thr Leu Trp Leu Thr Ser 275 280 285 Leu Asn Ala Cys Leu Asp Pro Phe Ile Tyr Phe Phe Leu Cys Lys Ser 290 295 300 Phe Arg Asn Ser Leu Ile Ser Met Leu Lys Cys Pro Asn Ser Ala Thr 305 310 315 320 Ser Leu Ser Gln Asp Asn Arg Lys Lys Glu Gln Asp Gly Gly Asp Pro 325 330 335 Asn Glu Glu Thr Pro Met 340 <210> 57 <211> 283 <212> PRT <213> Homo sapiens <400> 57 Met Val Ser Ala Ala Ala Pro Ser Leu Leu Ile Leu Leu Leu Leu Leu 1 5 10 15 Leu Gly Ser Val Pro Ala Thr Asp Ala Arg Ser Val Pro Leu Lys Ala 20 25 30 Thr Phe Leu Glu Asp Val Ala Gly Ser Gly Glu Ala Glu Gly Ser Ser 35 40 45 Ala Ser Ser Pro Ser Leu Pro Pro Pro Trp Thr Pro Ala Leu Ser Pro 50 55 60 Thr Ser Met Gly Pro Gln Pro Ile Thr Leu Gly Gly Pro Ser Pro Pro 65 70 75 80 Thr Asn Phe Leu Asp Gly Ile Val Asp Phe Phe Arg Gln Tyr Val Met 85 90 95 Leu Ile Ala Val Val Gly Ser Leu Ala Phe Leu Leu Met Phe Ile Val 100 105 110 Cys Ala Ala Val Ile Thr Arg Gln Lys Gln Lys Ala Ser Ala Tyr Tyr 115 120 125 Pro Ser Ser Phe Pro Lys Lys Lys Tyr Val Asp Gln Ser Asp Arg Ala 130 135 140 Gly Gly Pro Arg Ala Phe Ser Glu Val Pro Asp Arg Ala Pro Asp Ser 145 150 155 160 Arg Pro Glu Glu Ala Leu Asp Ser Ser Arg Gln Leu Gln Ala Asp Ile 165 170 175 Leu Ala Ala Thr Gln Asn Leu Lys Ser Pro Thr Arg Ala Ala Leu Gly 180 185 190 Gly Gly Asp Gly Ala Arg Met Val Glu Gly Arg Gly Ala Glu Glu Glu 195 200 205 Glu Lys Gly Ser Gln Glu Gly Asp Gln Glu Val Gln Gly His Gly Val 210 215 220 Pro Val Glu Thr Pro Glu Ala Gln Glu Glu Pro Cys Ser Gly Val Leu 225 230 235 240 Glu Gly Ala Val Val Ala Gly Glu Gly Gln Gly Glu Leu Glu Gly Ser 245 250 255 Leu Leu Leu Ala Gln Glu Ala Gln Gly Pro Val Gly Pro Pro Glu Ser 260 265 270 Pro Cys Ala Cys Ser Ser Val His Pro Ser Val 275 280 <210> 58 <211> 254 <212> PRT <213> Homo sapiens <400> 58 Met Ala Ile Ser Gly Val Pro Val Leu Gly Phe Phe Ile Ile Ala Val 1 5 10 15 Leu Met Ser Ala Gln Glu Ser Trp Ala Ile Lys Glu Glu His Val Ile 20 25 30 Ile Gln Ala Glu Phe Tyr Leu Asn Pro Asp Gln Ser Gly Glu Phe Met 35 40 45 Phe Asp Phe Asp Gly Asp Glu Ile Phe His Val Asp Met Ala Lys Lys 50 55 60 Glu Thr Val Trp Arg Leu Glu Glu Phe Gly Arg Phe Ala Ser Phe Glu 65 70 75 80 Ala Gln Gly Ala Leu Ala Asn Ile Ala Val Asp Lys Ala Asn Leu Glu 85 90 95 Ile Met Thr Lys Arg Ser Asn Tyr Thr Pro Ile Thr Asn Val Pro Pro 100 105 110 Glu Val Thr Val Leu Thr Asn Ser Pro Val Glu Leu Arg Glu Pro Asn 115 120 125 Val Leu Ile Cys Phe Ile Asp Lys Phe Thr Pro Pro Val Val Asn Val 130 135 140 Thr Trp Leu Arg Asn Gly Lys Pro Val Thr Thr Gly Val Ser Glu Thr 145 150 155 160 Val Phe Leu Pro Arg Glu Asp His Leu Phe Arg Lys Phe His Tyr Leu 165 170 175 Pro Phe Leu Pro Ser Thr Glu Asp Val Tyr Asp Cys Arg Val Glu His 180 185 190 Trp Gly Leu Asp Glu Pro Leu Leu Lys His Trp Glu Phe Asp Ala Pro 195 200 205 Ser Pro Leu Pro Glu Thr Thr Glu Asn Val Val Cys Ala Leu Gly Leu 210 215 220 Thr Val Gly Leu Val Gly Ile Ile Ile Gly Thr Ile Phe Ile Ile Lys 225 230 235 240 Gly Val Arg Lys Ser Asn Ala Ala Glu Arg Arg Gly Pro Leu 245 250 <210> 59 <211> 20 <212> PRT <213> Homo sapiens <400> 59 Gly Gly Thr Ala Thr Gly Thr Thr Thr Cys Ala Thr Cys Cys Ala Cys 1 5 10 15 Thr Gly Gly Cys 20 <210> 60 <211> 20 <212> DNA <213> Homo sapiens <400> 60 gtctatacaa aggaagacct 20 <210> 61 <211> 7844 <212> DNA <213> artificial sequence <220> <223> vector PUC_AAVS1_p-Resp-(PU.1-CEBPB) <400> 61 gaactttaaa agtgctcatc attggaaaac gttcttcggg gcgaaaactc tcaaggatct 60 taccgctgtt gagatccagt tcgatgtaac ccactcgtgc acccaactga tcttcagcat 120 cttttacttt caccagcgtt tctgggtgag caaaaacagg aaggcaaaat gccgcaaaaa 180 agggaataag ggcgacacgg aaatgttgaa tactcatact cttccttttt caatattatt 240 gaagcattta tcagggttat tgtctcatga gcggatacat atttgaatgt atttagaaaa 300 ataaacaaat aggggttccg cgcacatttc cccgaaaagt gccacctgac gtctaagaaa 360 ccattattat catgacatta acctataaaa ataggcgtat cacgaggccc tttcgtctcg 420 cgcgtttcgg tgatgacggt gaaaacctct gacacatgca gctcccggag acggtcacag 480 cttgtctgta agcggatgcc gggagcagac aagcccgtca gggcgcgtca gcgggtgttg 540 gcgggtgtcg gggctggctt aactatgcgg catcagagca gattgtactg agagtgcacc 600 atatgcggtg tgaaataccg cacagatgcg taaggagaaa ataccgcatc aggcgccatt 660 cgccattcag gctgcgcaac tgttgggaag ggcgatcggt gcgggcctct tcgctattac 720 gccagctggc gaaaggggga tgtgctgcaa ggcgattaag ttgggtaacg ccagggtttt 780 cccagtcacg acgttgtaaa acgacggcca gtgaattgtg ctttctctga ccagcattct 840 ctcccctggg cctgtgccgc tttctgtctg tagcttgtgg cctgggtcac ctctacggct 900 ggcccagatc cttccctgcc gcctccttca ggttccgtct tcctccactc cctcttcccc 960 ttgctctctg ctgtgttgct gcccaaggat gctctttccg gagcacttcc ttctcggcgc 1020 tgcaccacgt gatgtcctct gagcggatcc tccccgtgtc tgggtcctct ccgggcatct 1080 ctcctccctc acccaacccc atgccgtctt cactcgctgg gttccctttt ccttctcctt 1140 ctggggcctg tgccatctct cgtttcttag gatggccttc tccgacggat gtctcccttg 1200 cgtcccgcct ccccttcttg taggcctgca tcatcaccgt ttttctggac aaccccaaag 1260 taccccgtct ccctggcttt agccacctct ccatcctctt gctttctttg cctggacacc 1320 ccgttctcct gtggattcgg gtcacctctc actcctttca tttgggcagc tcccctaccc 1380 cccttacctc tctagtctgt gctagctctt ccagccccct gtcatggcat cttccagggg 1440 tccgagagct cagctagtct tcttcctcca acccgggccc ctatgtccac ttcaggacag 1500 catgtttgct gcctccaggg atcctgtgtc cccgagctgg gaccacctta tattcccagg 1560 gccggttaat gtggctctgg ttctgggtac ttttatctgt cccctccacc ccacagtggg 1620 gcaagcttct gacctcttct cttcctccca cagggcctcg agagatctgg cagcggagag 1680 ggcagaggaa gtcttctaac atgcggtgac gtggaggaga atcccggccc taggctcgag 1740 atgaccgagt acaagcccac ggtgcgcctc gccacccgcg acgacgtccc cagggccgta 1800 cgcaccctcg ccgccgcgtt cgccgactac cccgccacgc gccacaccgt cgatccggac 1860 cgccacatcg agcgggtcac cgagctgcaa gaactcttcc tcacgcgcgt cgggctcgac 1920 atcggcaagg tgtgggtcgc ggacgacggc gccgcggtgg cggtctggac cacgccggag 1980 agcgtcgaag cgggggcggt gttcgccgag atcggcccgc gcatggccga gttgagcggt 2040 tcccggctgg ccgcgcagca acagatggaa ggcctcctgg cgccgcaccg gcccaaggag 2100 cccgcgtggt tcctggccac cgtcggcgtc tcgcccgacc accagggcaa gggtctgggc 2160 agcgccgtcg tgctccccgg agtggaggcg gccgagcgcg ccggggtgcc cgccttcctg 2220 gagacctccg cgccccgcaa cctccccttc tacgagcggc tcggcttcac cgtcaccgcc 2280 gacgtcgagg tgcccgaagg accgcgcacc tggtgcatga cccgcaagcc cggtgcctga 2340 tctagagggc ccgtttaaac ccgctgatca gcctcgactg tgccttctag ttgccagcca 2400 tctgttgttt gcccctcccc cgtgccttcc ttgaccctgg aaggtgccac tcccactgtc 2460 ctttcctaat aaaatgagga aattgcatcg cattgtctga gtaggtgtca ttctattctg 2520 gggggtgggg tggggcagga cagcaagggg gaggattggg aagacaatag caggcatgct 2580 ggggatgcgg tgggctctat ggtcactcga gtttactccc tatcagtgat agagaacgta 2640 tgaagagttt actccctatc agtgatagag aacgtatgca gactttactc cctatcagtg 2700 atagagaacg tataaggagt ttactcccta tcagtgatag agaacgtatg accagtttac 2760 tccctatcag tgatagagaa cgtatctaca gtttactccc tatcagtgat agagaacgta 2820 tatccagttt actccctatc agtgatagag aacgtatgtc gaggtaggcg tgtacggtgg 2880 gcgcctataa aagcagagct cgtttagtga accgtcagat cgcctggagc aattccacaa 2940 cacttttgtc ttatacttac tagtgccacc atgttacagg cgtgcaaaat ggaagggttt 3000 cccctcgtcc cccctccatc agaagacctg gtgccctatg acacggatct ataccaacgc 3060 caaacgcacg agtattaccc ctatctcagc agtgatgggg agagccatag cgaccattac 3120 tgggacttcc acccccacca cgtgcacagc gagttcgaga gcttcgccga gaacaacttc 3180 acggagctcc agagcgtgca gcccccgcag ctgcagcagc tctaccgcca catggagctg 3240 gagcagatgc acgtcctcga tacccccatg gtgccacccc atcccagtct tggccaccag 3300 gtctcctacc tgccccggat gtgcctccag tacccatccc tgtccccagc ccagcccagc 3360 tcagatgagg aggagggcga gcggcagagc cccccactgg aggtgtctga cggcgaggcg 3420 gatggcctgg agcccgggcc tgggctcctg cctggggaga caggcagcaa gaagaagatc 3480 cgcctgtacc agttcctgtt ggacctgctc cgcagcggcg acatgaagga cagcatctgg 3540 tgggtggaca aggacaaggg caccttccag ttctcgtcca agcacaagga ggcgctggcg 3600 caccgctggg gcatccagaa gggcaaccgc aagaagatga cctaccagaa gatggcgcgc 3660 gcgctgcgca actacggcaa gacgggcgag gtcaagaagg tgaagaagaa gctcacctac 3720 cagttcagcg gcgaagtgct gggccgcggg ggcctggccg agcggcgcca cccgccccac 3780 ggatcgggag agggcagggg aagtcttcta acatgcgggg acgtggagga aaatcccggc 3840 cccatgcaac gcctggtggc ctgggaccca gcatgtctcc ccctgccgcc gccgccgcct 3900 gcctttaaat ccatggaagt ggccaacttc tactacgagg cggactgctt ggctgctgcg 3960 tacggcggca aggcggcccc cgcggcgccc cccgcggcca gacccgggcc gcgccccccc 4020 gccggcgagc tgggcagcat cggcgaccac gagcgcgcca tcgacttcag cccgtacctg 4080 gagccgctgg gcgcgccgca ggccccggcg cccgccacgg ccacggacac cttcgaggcg 4140 gctccgcccg cgcccgcccc cgcgcccgcc tcctccgggc agcaccacga cttcctctcc 4200 gacctcttct ccgacgacta cgggggcaag aactgcaaga agccggccga gtacggctac 4260 gtgagcctgg ggcgcctggg ggccgccaag ggcgcgctgc accccggctg cttcgcgccc 4320 ctgcacccac cgcccccgcc gccgccgccg cccgccgagc tcaaggcgga gccgggcttc 4380 gagcccgcgg actgcaagcg gaaggaggag gccggggcgc cgggcggcgg cgcaggcatg 4440 gcggcgggct tcccgtacgc gctgcgcgct tacctcggct accaggcggt gccgagcggc 4500 agcagcggga gcctctccac gtcctcctcg tccagcccgc ccggcacgcc gagccccgct 4560 gacgccaagg cgcccccgac cgcctgctac gcgggggccg cgccggcgcc ctcgcaggtc 4620 aagagcaagg ccaagaagac cgtggacaag cacagcgacg agtacaagat ccggcgcgag 4680 cgcaacaaca tcgccgtgcg caagagccgc gacaaggcca agatgcgcaa cctggagacg 4740 cagcacaagg tcctggagct cacggccgag aacgagcggc tgcagaagaa ggtggagcag 4800 ctgtcgcgcg agctcagcac cctgcggaac ttgttcaagc agctgcccga gcccctgctc 4860 gcctcctccg gccactgcta ggaattcgag ctcggtaccc ggggatcctc tagtcagctg 4920 acgcgtgcta gcgcggccgc atcgataagc ttgtcgacga tatctctaga ggatcataat 4980 cagccatacc acatttgtag aggttttact tgctttaaaa aacctcccac acctccccct 5040 gaacctgaaa cataaaatga atgcaattgt tgttgttaac ttgtttattg cagcttataa 5100 tggttacaaa taaagcaata gcatcacaaa tttcacaaat aaagcatttt tttcactgcc 5160 ttgacagtac tcttaagtcg acttactagg gacaggattg gtgacagaaa agccccatcc 5220 ttaggcctcc tccttcctag tctcctgata ttgggtctaa cccccacctc ctgttaggca 5280 gattccttat ctggtgacac acccccattt cctggagcca tctctctcct tgccagaacc 5340 tctaaggttt gcttacgatg gagccagaga ggatcctggg agggagagct tggcaggggg 5400 tgggagggaa gggggggatg cgtgacctgc ccggttctca gtggccaccc tgcgctaccc 5460 tctcccagaa cctgagctgc tctgacgcgg ctgtctggtg cgtttcactg atcctggtgc 5520 tgcagcttcc ttacacttcc caagaggaga agcagtttgg aaaaacaaaa tcagaataag 5580 ttggtcctga gttctaactt tggctcttca cctttctagt ccccaattta tattgttcct 5640 ccgtgcgtca gttttacctg tgagataagg ccagtagcca gccccgtcct ggcagggctg 5700 tggtgaggag gggggtgtcc gtgtggaaaa ctccctttgt gagaatggtg cgtcctaggt 5760 gttcaccagg tcgtggccgc ctctactccc tttctctttc tccatccttc tttccttaaa 5820 gagtccccag tgctatctgg gacatattcc tccgcccaga gcagggtccc gcttccctaa 5880 ggccctgctc tgggcttctg ggtttgagtc cttggcaagc ccaggagagg cgctcaggct 5940 tccctgtccc ccttcctcgt ccaccatctc atgcccctgg ctctcctgcc ccttccctac 6000 aggggttcct ggctctgctc taagcttggc gtaatcatgg tcatagctgt ttcctgtgtg 6060 aaattgttat ccgctcacaa ttccacacaa catacgagcc ggaagcataa agtgtaaagc 6120 ctggggtgcc taatgagtga gctaactcac attaattgcg ttgcgctcac tgcccgcttt 6180 ccagtcggga aacctgtcgt gccagctgca ttaatgaatc ggccaacgcg cggggagagg 6240 cggtttgcgt attgggcgct cttccgcttc ctcgctcact gactcgctgc gctcggtcgt 6300 tcggctgcgg cgagcggtat cagctcactc aaaggcggta atacggttat ccacagaatc 6360 aggggataac gcaggaaaga acatgtgagc aaaaggccag caaaaggcca ggaaccgtaa 6420 aaaggccgcg ttgctggcgt ttttccatag gctccgcccc cctgacgagc atcacaaaaa 6480 tcgacgctca agtcagaggt ggcgaaaccc gacaggacta taaagatacc aggcgtttcc 6540 ccctggaagc tccctcgtgc gctctcctgt tccgaccctg ccgcttaccg gatacctgtc 6600 cgcctttctc ccttcgggaa gcgtggcgct ttctcatagc tcacgctgta ggtatctcag 6660 ttcggtgtag gtcgttcgct ccaagctggg ctgtgtgcac gaaccccccg ttcagcccga 6720 ccgctgcgcc ttatccggta actatcgtct tgagtccaac ccggtaagac acgacttatc 6780 gccactggca gcagccactg gtaacaggat tagcagagcg aggtatgtag gcggtgctac 6840 agagttcttg aagtggtggc ctaactacgg ctacactaga agaacagtat ttggtatctg 6900 cgctctgctg aagccagtta ccttcggaaa aagagttggt agctcttgat ccggcaaaca 6960 aaccaccgct ggtagcggtg gtttttttgt ttgcaagcag cagattacgc gcagaaaaaa 7020 aggatctcaa gaagatcctt tgatcttttc tacggggtct gacgctcagt ggaacgaaaa 7080 ctcacgttaa gggattttgg tcatgagatt atcaaaaagg atcttcacct agatcctttt 7140 aaattaaaaa tgaagtttta aatcaatcta aagtatatat gagtaaactt ggtctgacag 7200 ttaccaatgc ttaatcagtg aggcacctat ctcagcgatc tgtctatttc gttcatccat 7260 agttgcctga ctccccgtcg tgtagataac tacgatacgg gagggcttac catctggccc 7320 cagtgctgca atgataccgc gagacccacg ctcaccggct ccagatttat cagcaataaa 7380 ccagccagcc ggaagggccg agcgcagaag tggtcctgca actttatccg cctccatcca 7440 gtctattaat tgttgccggg aagctagagt aagtagttcg ccagttaata gtttgcgcaa 7500 cgttgttgcc attgctacag gcatcgtggt gtcacgctcg tcgtttggta tggcttcatt 7560 cagctccggt tcccaacgat caaggcgagt tacatgatcc cccatgttgt gcaaaaaagc 7620 ggttagctcc ttcggtcctc cgatcgttgt cagaagtaag ttggccgcag tgttatcact 7680 catggttatg gcagcactgc ataattctct tactgtcatg ccatccgtaa gatgcttttc 7740 tgtgactggt gagtactcaa ccaagtcatt ctgagaatag tgtatgcggc gaccgagttg 7800 ctcttgcccg gcgtcaatac gggataatac cgcgccacat agca 7844 <210> 62 <211> 8087 <212> DNA <213> artificial sequence <220> <223> vector pUC_AAVS1_p-Resp-(PU.1-IRF8) <400> 62 gaactttaaa agtgctcatc attggaaaac gttcttcggg gcgaaaactc tcaaggatct 60 taccgctgtt gagatccagt tcgatgtaac ccactcgtgc acccaactga tcttcagcat 120 cttttacttt caccagcgtt tctgggtgag caaaaacagg aaggcaaaat gccgcaaaaa 180 agggaataag ggcgacacgg aaatgttgaa tactcatact cttccttttt caatattatt 240 gaagcattta tcagggttat tgtctcatga gcggatacat atttgaatgt atttagaaaa 300 ataaacaaat aggggttccg cgcacatttc cccgaaaagt gccacctgac gtctaagaaa 360 ccattattat catgacatta acctataaaa ataggcgtat cacgaggccc tttcgtctcg 420 cgcgtttcgg tgatgacggt gaaaacctct gacacatgca gctcccggag acggtcacag 480 cttgtctgta agcggatgcc gggagcagac aagcccgtca gggcgcgtca gcgggtgttg 540 gcgggtgtcg gggctggctt aactatgcgg catcagagca gattgtactg agagtgcacc 600 atatgcggtg tgaaataccg cacagatgcg taaggagaaa ataccgcatc aggcgccatt 660 cgccattcag gctgcgcaac tgttgggaag ggcgatcggt gcgggcctct tcgctattac 720 gccagctggc gaaaggggga tgtgctgcaa ggcgattaag ttgggtaacg ccagggtttt 780 cccagtcacg acgttgtaaa acgacggcca gtgaattgtg ctttctctga ccagcattct 840 ctcccctggg cctgtgccgc tttctgtctg tagcttgtgg cctgggtcac ctctacggct 900 ggcccagatc cttccctgcc gcctccttca ggttccgtct tcctccactc cctcttcccc 960 ttgctctctg ctgtgttgct gcccaaggat gctctttccg gagcacttcc ttctcggcgc 1020 tgcaccacgt gatgtcctct gagcggatcc tccccgtgtc tgggtcctct ccgggcatct 1080 ctcctccctc acccaacccc atgccgtctt cactcgctgg gttccctttt ccttctcctt 1140 ctggggcctg tgccatctct cgtttcttag gatggccttc tccgacggat gtctcccttg 1200 cgtcccgcct ccccttcttg taggcctgca tcatcaccgt ttttctggac aaccccaaag 1260 taccccgtct ccctggcttt agccacctct ccatcctctt gctttctttg cctggacacc 1320 ccgttctcct gtggattcgg gtcacctctc actcctttca tttgggcagc tcccctaccc 1380 cccttacctc tctagtctgt gctagctctt ccagccccct gtcatggcat cttccagggg 1440 tccgagagct cagctagtct tcttcctcca acccgggccc ctatgtccac ttcaggacag 1500 catgtttgct gcctccaggg atcctgtgtc cccgagctgg gaccacctta tattcccagg 1560 gccggttaat gtggctctgg ttctgggtac ttttatctgt cccctccacc ccacagtggg 1620 gcaagcttct gacctcttct cttcctccca cagggcctcg agagatctgg cagcggagag 1680 ggcagaggaa gtcttctaac atgcggtgac gtggaggaga atcccggccc taggctcgag 1740 atgaccgagt acaagcccac ggtgcgcctc gccacccgcg acgacgtccc cagggccgta 1800 cgcaccctcg ccgccgcgtt cgccgactac cccgccacgc gccacaccgt cgatccggac 1860 cgccacatcg agcgggtcac cgagctgcaa gaactcttcc tcacgcgcgt cgggctcgac 1920 atcggcaagg tgtgggtcgc ggacgacggc gccgcggtgg cggtctggac cacgccggag 1980 agcgtcgaag cgggggcggt gttcgccgag atcggcccgc gcatggccga gttgagcggt 2040 tcccggctgg ccgcgcagca acagatggaa ggcctcctgg cgccgcaccg gcccaaggag 2100 cccgcgtggt tcctggccac cgtcggcgtc tcgcccgacc accagggcaa gggtctgggc 2160 agcgccgtcg tgctccccgg agtggaggcg gccgagcgcg ccggggtgcc cgccttcctg 2220 gagacctccg cgccccgcaa cctccccttc tacgagcggc tcggcttcac cgtcaccgcc 2280 gacgtcgagg tgcccgaagg accgcgcacc tggtgcatga cccgcaagcc cggtgcctga 2340 tctagagggc ccgtttaaac ccgctgatca gcctcgactg tgccttctag ttgccagcca 2400 tctgttgttt gcccctcccc cgtgccttcc ttgaccctgg aaggtgccac tcccactgtc 2460 ctttcctaat aaaatgagga aattgcatcg cattgtctga gtaggtgtca ttctattctg 2520 gggggtgggg tggggcagga cagcaagggg gaggattggg aagacaatag caggcatgct 2580 ggggatgcgg tgggctctat ggtcactcga gtttactccc tatcagtgat agagaacgta 2640 tgaagagttt actccctatc agtgatagag aacgtatgca gactttactc cctatcagtg 2700 atagagaacg tataaggagt ttactcccta tcagtgatag agaacgtatg accagtttac 2760 tccctatcag tgatagagaa cgtatctaca gtttactccc tatcagtgat agagaacgta 2820 tatccagttt actccctatc agtgatagag aacgtatgtc gaggtaggcg tgtacggtgg 2880 gcgcctataa aagcagagct cgtttagtga accgtcagat cgcctggagc aattccacaa 2940 cacttttgtc ttatacttac tagtgccacc atgttacagg cgtgcaaaat ggaagggttt 3000 cccctcgtcc cccctccatc agaagacctg gtgccctatg acacggatct ataccaacgc 3060 caaacgcacg agtattaccc ctatctcagc agtgatgggg agagccatag cgaccattac 3120 tgggacttcc acccccacca cgtgcacagc gagttcgaga gcttcgccga gaacaacttc 3180 acggagctcc agagcgtgca gcccccgcag ctgcagcagc tctaccgcca catggagctg 3240 gagcagatgc acgtcctcga tacccccatg gtgccacccc atcccagtct tggccaccag 3300 gtctcctacc tgccccggat gtgcctccag tacccatccc tgtccccagc ccagcccagc 3360 tcagatgagg aggagggcga gcggcagagc cccccactgg aggtgtctga cggcgaggcg 3420 gatggcctgg agcccgggcc tgggctcctg cctggggaga caggcagcaa gaagaagatc 3480 cgcctgtacc agttcctgtt ggacctgctc cgcagcggcg acatgaagga cagcatctgg 3540 tgggtggaca aggacaaggg caccttccag ttctcgtcca agcacaagga ggcgctggcg 3600 caccgctggg gcatccagaa gggcaaccgc aagaagatga cctaccagaa gatggcgcgc 3660 gcgctgcgca actacggcaa gacgggcgag gtcaagaagg tgaagaagaa gctcacctac 3720 cagttcagcg gcgaagtgct gggccgcggg ggcctggccg agcggcgcca cccgccccac 3780 ggatcgggag agggcagggg aagtcttcta acatgcgggg acgtggagga aaatcccggc 3840 cccatgtgtg accggaatgg tggtcggcgg cttcgacagt ggctgatcga gcagattgac 3900 agtagcatgt atccaggact gatttgggag aatgaggaga agagcatgtt ccggatccct 3960 tggaaacacg ctggcaagca agattataat caggaagtgg atgcctccat ttttaaggcc 4020 tgggcagttt ttaaagggaa gtttaaagaa ggggacaaag ctgaaccagc cacttggaag 4080 acgaggttac gctgtgcttt gaataagagc ccagattttg aggaagtgac ggaccggtcc 4140 caactggaca tttccgagcc atacaaagtt taccgaattg ttcctgagga agagcaaaaa 4200 tgcaaactag gcgtggcaac tgctggctgc gtgaatgaag ttacagagat ggagtgcggt 4260 cgctctgaaa tcgacgagct gatcaaggag ccttctgtgg acgattacat ggggatgatc 4320 aaaaggagcc cttccccgcc ggaggcctgt cggagtcagc tccttccaga ctggtgggcg 4380 cagcagccca gcacaggcgt gccgctggtg acggggtaca ccacctacga cgcgcaccat 4440 tcagcattct cccagatggt gatcagcttc tactatgggg gcaagctggt gggccaggcc 4500 accaccacct gccccgaggg ctgccgcctg tccctgagcc agcctgggct gcccggcacc 4560 aagctgtatg ggcccgaggg cctggagctg gtgcgcttcc cgccggccga cgccatcccc 4620 agcgagcgac agaggcaggt gacgcggaag ctgttcgggc acctggagcg cggggtgctg 4680 ctgcacagca gccggcaggg cgtgttcgtc aagcggctgt gccagggccg cgtgttctgc 4740 agcggcaacg ccgtggtgtg caaaggcagg cccaacaagc tggagcgtga tgaggtggtc 4800 caggtcttcg acaccagcca gttcttccga gagctgcagc agttctataa cagccagggc 4860 cggcttcctg acggcagggt ggtgctgtgc tttggggaag agtttccgga tatggccccc 4920 ttgcgctcca aactcattct cgtgcagatt gagcagctgt atgtccggca actggcagaa 4980 gaggctggga agagctgtgg agccggctct gtgatgcagg cccccgagga gccgccgcca 5040 gaccaggtct tccggatgtt tccagatatt tgtgcctcac accagagatc atttttcaga 5100 gaaaaccaac agatcaccgt ctaagaattc gagctcggta cccggggatc ctctagtcag 5160 ctgacgcgtg ctagcgcggc cgcatcgata agcttgtcga cgatatctct agaggatcat 5220 aatcagccat accacatttg tagaggtttt acttgcttta aaaaacctcc cacacctccc 5280 cctgaacctg aaacataaaa tgaatgcaat tgttgttgtt aacttgttta ttgcagctta 5340 taatggttac aaataaagca atagcatcac aaatttcaca aataaagcat ttttttcact 5400 gccttgacag tactcttaag tcgacttact agggacagga ttggtgacag aaaagcccca 5460 tccttaggcc tcctccttcc tagtctcctg atattgggtc taacccccac ctcctgttag 5520 gcagattcct tatctggtga cacaccccca tttcctggag ccatctctct ccttgccaga 5580 acctctaagg tttgcttacg atggagccag agaggatcct gggagggaga gcttggcagg 5640 gggtgggagg gaaggggggg atgcgtgacc tgcccggttc tcagtggcca ccctgcgcta 5700 ccctctccca gaacctgagc tgctctgacg cggctgtctg gtgcgtttca ctgatcctgg 5760 tgctgcagct tccttacact tcccaagagg agaagcagtt tggaaaaaca aaatcagaat 5820 aagttggtcc tgagttctaa ctttggctct tcacctttct agtccccaat ttatattgtt 5880 cctccgtgcg tcagttttac ctgtgagata aggccagtag ccagccccgt cctggcaggg 5940 ctgtggtgag gaggggggtg tccgtgtgga aaactccctt tgtgagaatg gtgcgtccta 6000 ggtgttcacc aggtcgtggc cgcctctact ccctttctct ttctccatcc ttctttcctt 6060 aaagagtccc cagtgctatc tgggacatat tcctccgccc agagcagggt cccgcttccc 6120 taaggccctg ctctgggctt ctgggtttga gtccttggca agcccaggag aggcgctcag 6180 gcttccctgt cccccttcct cgtccaccat ctcatgcccc tggctctcct gccccttccc 6240 tacaggggtt cctggctctg ctctaagctt ggcgtaatca tggtcatagc tgtttcctgt 6300 gtgaaattgt tatccgctca caattccaca caacatacga gccggaagca taaagtgtaa 6360 agcctggggt gcctaatgag tgagctaact cacattaatt gcgttgcgct cactgcccgc 6420 tttccagtcg ggaaacctgt cgtgccagct gcattaatga atcggccaac gcgcggggag 6480 aggcggtttg cgtattgggc gctcttccgc ttcctcgctc actgactcgc tgcgctcggt 6540 cgttcggctg cggcgagcgg tatcagctca ctcaaaggcg gtaatacggt tatccacaga 6600 atcaggggat aacgcaggaa agaacatgtg agcaaaaggc cagcaaaagg ccaggaaccg 6660 taaaaaggcc gcgttgctgg cgtttttcca taggctccgc ccccctgacg agcatcacaa 6720 aaatcgacgc tcaagtcaga ggtggcgaaa cccgacagga ctataaagat accaggcgtt 6780 tccccctgga agctccctcg tgcgctctcc tgttccgacc ctgccgctta ccggatacct 6840 gtccgccttt ctcccttcgg gaagcgtggc gctttctcat agctcacgct gtaggtatct 6900 cagttcggtg taggtcgttc gctccaagct gggctgtgtg cacgaacccc ccgttcagcc 6960 cgaccgctgc gccttatccg gtaactatcg tcttgagtcc aacccggtaa gacacgactt 7020 atcgccactg gcagcagcca ctggtaacag gattagcaga gcgaggtatg taggcggtgc 7080 tacagagttc ttgaagtggt ggcctaacta cggctacact agaagaacag tatttggtat 7140 ctgcgctctg ctgaagccag ttaccttcgg aaaaagagtt ggtagctctt gatccggcaa 7200 acaaaccacc gctggtagcg gtggtttttt tgtttgcaag cagcagatta cgcgcagaaa 7260 aaaaggatct caagaagatc ctttgatctt ttctacgggg tctgacgctc agtggaacga 7320 aaactcacgt taagggattt tggtcatgag attatcaaaa aggatcttca cctagatcct 7380 tttaaattaa aaatgaagtt ttaaatcaat ctaaagtata tatgagtaaa cttggtctga 7440 cagttaccaa tgcttaatca gtgaggcacc tatctcagcg atctgtctat ttcgttcatc 7500 catagttgcc tgactccccg tcgtgtagat aactacgata cgggagggct taccatctgg 7560 ccccagtgct gcaatgatac cgcgagaccc acgctcaccg gctccagatt tatcagcaat 7620 aaaccagcca gccggaaggg ccgagcgcag aagtggtcct gcaactttat ccgcctccat 7680 ccagtctatt aattgttgcc gggaagctag agtaagtagt tcgccagtta atagtttgcg 7740 caacgttgtt gccattgcta caggcatcgt ggtgtcacgc tcgtcgtttg gtatggcttc 7800 attcagctcc ggttcccaac gatcaaggcg agttacatga tcccccatgt tgtgcaaaaa 7860 agcggttagc tccttcggtc ctccgatcgt tgtcagaagt aagttggccg cagtgttatc 7920 actcatggtt atggcagcac tgcataattc tcttactgtc atgccatccg taagatgctt 7980 ttctgtgact ggtgagtact caaccaagtc attctgagaa tagtgtatgc ggcgaccgag 8040 ttgctcttgc ccggcgtcaa tacgggataa taccgcgcca catagca 8087 <210> 63 <211> 8255 <212> DNA <213> artificial sequence <220> <223> vector pUC_AAVS1_p-Resp-(PU.1-RUNX1) <400> 63 gaactttaaa agtgctcatc attggaaaac gttcttcggg gcgaaaactc tcaaggatct 60 taccgctgtt gagatccagt tcgatgtaac ccactcgtgc acccaactga tcttcagcat 120 cttttacttt caccagcgtt tctgggtgag caaaaacagg aaggcaaaat gccgcaaaaa 180 agggaataag ggcgacacgg aaatgttgaa tactcatact cttccttttt caatattatt 240 gaagcattta tcagggttat tgtctcatga gcggatacat atttgaatgt atttagaaaa 300 ataaacaaat aggggttccg cgcacatttc cccgaaaagt gccacctgac gtctaagaaa 360 ccattattat catgacatta acctataaaa ataggcgtat cacgaggccc tttcgtctcg 420 cgcgtttcgg tgatgacggt gaaaacctct gacacatgca gctcccggag acggtcacag 480 cttgtctgta agcggatgcc gggagcagac aagcccgtca gggcgcgtca gcgggtgttg 540 gcgggtgtcg gggctggctt aactatgcgg catcagagca gattgtactg agagtgcacc 600 atatgcggtg tgaaataccg cacagatgcg taaggagaaa ataccgcatc aggcgccatt 660 cgccattcag gctgcgcaac tgttgggaag ggcgatcggt gcgggcctct tcgctattac 720 gccagctggc gaaaggggga tgtgctgcaa ggcgattaag ttgggtaacg ccagggtttt 780 cccagtcacg acgttgtaaa acgacggcca gtgaattgtg ctttctctga ccagcattct 840 ctcccctggg cctgtgccgc tttctgtctg tagcttgtgg cctgggtcac ctctacggct 900 ggcccagatc cttccctgcc gcctccttca ggttccgtct tcctccactc cctcttcccc 960 ttgctctctg ctgtgttgct gcccaaggat gctctttccg gagcacttcc ttctcggcgc 1020 tgcaccacgt gatgtcctct gagcggatcc tccccgtgtc tgggtcctct ccgggcatct 1080 ctcctccctc acccaacccc atgccgtctt cactcgctgg gttccctttt ccttctcctt 1140 ctggggcctg tgccatctct cgtttcttag gatggccttc tccgacggat gtctcccttg 1200 cgtcccgcct ccccttcttg taggcctgca tcatcaccgt ttttctggac aaccccaaag 1260 taccccgtct ccctggcttt agccacctct ccatcctctt gctttctttg cctggacacc 1320 ccgttctcct gtggattcgg gtcacctctc actcctttca tttgggcagc tcccctaccc 1380 cccttacctc tctagtctgt gctagctctt ccagccccct gtcatggcat cttccagggg 1440 tccgagagct cagctagtct tcttcctcca acccgggccc ctatgtccac ttcaggacag 1500 catgtttgct gcctccaggg atcctgtgtc cccgagctgg gaccacctta tattcccagg 1560 gccggttaat gtggctctgg ttctgggtac ttttatctgt cccctccacc ccacagtggg 1620 gcaagcttct gacctcttct cttcctccca cagggcctcg agagatctgg cagcggagag 1680 ggcagaggaa gtcttctaac atgcggtgac gtggaggaga atcccggccc taggctcgag 1740 atgaccgagt acaagcccac ggtgcgcctc gccacccgcg acgacgtccc cagggccgta 1800 cgcaccctcg ccgccgcgtt cgccgactac cccgccacgc gccacaccgt cgatccggac 1860 cgccacatcg agcgggtcac cgagctgcaa gaactcttcc tcacgcgcgt cgggctcgac 1920 atcggcaagg tgtgggtcgc ggacgacggc gccgcggtgg cggtctggac cacgccggag 1980 agcgtcgaag cgggggcggt gttcgccgag atcggcccgc gcatggccga gttgagcggt 2040 tcccggctgg ccgcgcagca acagatggaa ggcctcctgg cgccgcaccg gcccaaggag 2100 cccgcgtggt tcctggccac cgtcggcgtc tcgcccgacc accagggcaa gggtctgggc 2160 agcgccgtcg tgctccccgg agtggaggcg gccgagcgcg ccggggtgcc cgccttcctg 2220 gagacctccg cgccccgcaa cctccccttc tacgagcggc tcggcttcac cgtcaccgcc 2280 gacgtcgagg tgcccgaagg accgcgcacc tggtgcatga cccgcaagcc cggtgcctga 2340 tctagagggc ccgtttaaac ccgctgatca gcctcgactg tgccttctag ttgccagcca 2400 tctgttgttt gcccctcccc cgtgccttcc ttgaccctgg aaggtgccac tcccactgtc 2460 ctttcctaat aaaatgagga aattgcatcg cattgtctga gtaggtgtca ttctattctg 2520 gggggtgggg tggggcagga cagcaagggg gaggattggg aagacaatag caggcatgct 2580 ggggatgcgg tgggctctat ggtcactcga gtttactccc tatcagtgat agagaacgta 2640 tgaagagttt actccctatc agtgatagag aacgtatgca gactttactc cctatcagtg 2700 atagagaacg tataaggagt ttactcccta tcagtgatag agaacgtatg accagtttac 2760 tccctatcag tgatagagaa cgtatctaca gtttactccc tatcagtgat agagaacgta 2820 tatccagttt actccctatc agtgatagag aacgtatgtc gaggtaggcg tgtacggtgg 2880 gcgcctataa aagcagagct cgtttagtga accgtcagat cgcctggagc aattccacaa 2940 cacttttgtc ttatacttac tagtgccacc atgttacagg cgtgcaaaat ggaagggttt 3000 cccctcgtcc cccctccatc agaagacctg gtgccctatg acacggatct ataccaacgc 3060 caaacgcacg agtattaccc ctatctcagc agtgatgggg agagccatag cgaccattac 3120 tgggacttcc acccccacca cgtgcacagc gagttcgaga gcttcgccga gaacaacttc 3180 acggagctcc agagcgtgca gcccccgcag ctgcagcagc tctaccgcca catggagctg 3240 gagcagatgc acgtcctcga tacccccatg gtgccacccc atcccagtct tggccaccag 3300 gtctcctacc tgccccggat gtgcctccag tacccatccc tgtccccagc ccagcccagc 3360 tcagatgagg aggagggcga gcggcagagc cccccactgg aggtgtctga cggcgaggcg 3420 gatggcctgg agcccgggcc tgggctcctg cctggggaga caggcagcaa gaagaagatc 3480 cgcctgtacc agttcctgtt ggacctgctc cgcagcggcg acatgaagga cagcatctgg 3540 tgggtggaca aggacaaggg caccttccag ttctcgtcca agcacaagga ggcgctggcg 3600 caccgctggg gcatccagaa gggcaaccgc aagaagatga cctaccagaa gatggcgcgc 3660 gcgctgcgca actacggcaa gacgggcgag gtcaagaagg tgaagaagaa gctcacctac 3720 cagttcagcg gcgaagtgct gggccgcggg ggcctggccg agcggcgcca cccgccccac 3780 ggatcgggag agggcagggg aagtcttcta acatgcgggg acgtggagga aaatcccggc 3840 cccatggctt cagacagcat atttgagtca tttccttcgt acccacagtg cttcatgaga 3900 gaatgcatac ttggaatgaa tccttctaga gacgtccacg atgccagcac gagccgccgc 3960 ttcacgccgc cttccaccgc gctgagccca ggcaagatga gcgaggcgtt gccgctgggc 4020 gccccggacg ccggcgctgc cctggccggc aagctgagga gcggcgaccg cagcatggtg 4080 gaggtgctgg ccgaccaccc gggcgagctg gtgcgcaccg acagccccaa cttcctctgc 4140 tccgtgctgc ctacgcactg gcgctgcaac aagaccctgc ccatcgcttt caaggtggtg 4200 gccctagggg atgttccaga tggcactctg gtcactgtga tggctggcaa tgatgaaaac 4260 tactcggctg agctgagaaa tgctaccgca gccatgaaga accaggttgc aagatttaat 4320 gacctcaggt ttgtcggtcg aagtggaaga gggaaaagct tcactctgac catcactgtc 4380 ttcacaaacc caccgcaagt cgccacctac cacagagcca tcaaaatcac agtggatggg 4440 ccccgagaac ctcgaagaca tcggcagaaa ctagatgatc agaccaagcc cgggagcttg 4500 tccttttccg agcggctcag tgaactggag cagctgcggc gcacagccat gagggtcagc 4560 ccacaccacc cagcccccac gcccaaccct cgtgcctccc tgaaccactc cactgccttt 4620 aaccctcagc ctcagagtca gatgcaggat acaaggcaga tccaaccatc cccaccgtgg 4680 tcctacgatc agtcctacca atacctggga tccattgcct ctccttctgt gcacccagca 4740 acgcccattt cacctggacg tgccagcggc atgacaaccc tctctgcaga actttccagt 4800 cgactctcaa cggcacccga cctgacagcg ttcagcgacc cgcgccagtt ccccgcgctg 4860 ccctccatct ccgacccccg catgcactat ccaggcgcct tcacctactc cccgacgccg 4920 gtcacctcgg gcatcggcat cggcatgtcg gccatgggct cggccacgcg ctaccacacc 4980 tacctgccgc cgccctaccc cggctcgtcg caagcgcagg gaggcccgtt ccaagccagc 5040 tcgccctcct accacctgta ctacggcgcc tcggccggct cctaccagtt ctccatggtg 5100 ggcggcgagc gctcgccgcc gcgcatcctg ccgccctgca ccaacgcctc caccggctcc 5160 gcgctgctca accccagcct cccgaaccag agcgacgtgg tggaggccga gggcagccac 5220 agcaactccc cgaccaacat ggcgccctcc gcgcgcctgg aggaggccgt gtggaggccc 5280 tacaccggtt gagaattcga gctcggtacc cggggatcct ctagtcagct gacgcgtgct 5340 agcgcggccg catcgataag cttgtcgacg atatctctag aggatcataa tcagccatac 5400 cacatttgta gaggttttac ttgctttaaa aaacctccca cacctccccc tgaacctgaa 5460 acataaaatg aatgcaattg ttgttgttaa cttgtttatt gcagcttata atggttacaa 5520 ataaagcaat agcatcacaa atttcacaaa taaagcattt ttttcactgc cttgacagta 5580 ctcttaagtc gacttactag ggacaggatt ggtgacagaa aagccccatc cttaggcctc 5640 ctccttccta gtctcctgat attgggtcta acccccacct cctgttaggc agattcctta 5700 tctggtgaca cacccccatt tcctggagcc atctctctcc ttgccagaac ctctaaggtt 5760 tgcttacgat ggagccagag aggatcctgg gagggagagc ttggcagggg gtgggaggga 5820 agggggggat gcgtgacctg cccggttctc agtggccacc ctgcgctacc ctctcccaga 5880 acctgagctg ctctgacgcg gctgtctggt gcgtttcact gatcctggtg ctgcagcttc 5940 cttacacttc ccaagaggag aagcagtttg gaaaaacaaa atcagaataa gttggtcctg 6000 agttctaact ttggctcttc acctttctag tccccaattt atattgttcc tccgtgcgtc 6060 agttttacct gtgagataag gccagtagcc agccccgtcc tggcagggct gtggtgagga 6120 ggggggtgtc cgtgtggaaa actccctttg tgagaatggt gcgtcctagg tgttcaccag 6180 gtcgtggccg cctctactcc ctttctcttt ctccatcctt ctttccttaa agagtcccca 6240 gtgctatctg ggacatattc ctccgcccag agcagggtcc cgcttcccta aggccctgct 6300 ctgggcttct gggtttgagt ccttggcaag cccaggagag gcgctcaggc ttccctgtcc 6360 cccttcctcg tccaccatct catgcccctg gctctcctgc cccttcccta caggggttcc 6420 tggctctgct ctaagcttgg cgtaatcatg gtcatagctg tttcctgtgt gaaattgtta 6480 tccgctcaca attccacaca acatacgagc cggaagcata aagtgtaaag cctggggtgc 6540 ctaatgagtg agctaactca cattaattgc gttgcgctca ctgcccgctt tccagtcggg 6600 aaacctgtcg tgccagctgc attaatgaat cggccaacgc gcggggagag gcggtttgcg 6660 tattgggcgc tcttccgctt cctcgctcac tgactcgctg cgctcggtcg ttcggctgcg 6720 gcgagcggta tcagctcact caaaggcggt aatacggtta tccacagaat caggggataa 6780 cgcaggaaag aacatgtgag caaaaggcca gcaaaaggcc aggaaccgta aaaaggccgc 6840 gttgctggcg tttttccata ggctccgccc ccctgacgag catcacaaaa atcgacgctc 6900 aagtcagagg tggcgaaacc cgacaggact ataaagatac caggcgtttc cccctggaag 6960 ctccctcgtg cgctctcctg ttccgaccct gccgcttacc ggatacctgt ccgcctttct 7020 cccttcggga agcgtggcgc tttctcatag ctcacgctgt aggtatctca gttcggtgta 7080 ggtcgttcgc tccaagctgg gctgtgtgca cgaacccccc gttcagcccg accgctgcgc 7140 cttatccggt aactatcgtc ttgagtccaa cccggtaaga cacgacttat cgccactggc 7200 agcagccact ggtaacagga ttagcagagc gaggtatgta ggcggtgcta cagagttctt 7260 gaagtggtgg cctaactacg gctacactag aagaacagta tttggtatct gcgctctgct 7320 gaagccagtt accttcggaa aaagagttgg tagctcttga tccggcaaac aaaccaccgc 7380 tggtagcggt ggtttttttg tttgcaagca gcagattacg cgcagaaaaa aaggatctca 7440 agaagatcct ttgatctttt ctacggggtc tgacgctcag tggaacgaaa actcacgtta 7500 agggattttg gtcatgagat tatcaaaaag gatcttcacc tagatccttt taaattaaaa 7560 atgaagtttt aaatcaatct aaagtatata tgagtaaact tggtctgaca gttaccaatg 7620 cttaatcagt gaggcaccta tctcagcgat ctgtctattt cgttcatcca tagttgcctg 7680 actccccgtc gtgtagataa ctacgatacg ggagggctta ccatctggcc ccagtgctgc 7740 aatgataccg cgagacccac gctcaccggc tccagattta tcagcaataa accagccagc 7800 cggaagggcc gagcgcagaa gtggtcctgc aactttatcc gcctccatcc agtctattaa 7860 ttgttgccgg gaagctagag taagtagttc gccagttaat agtttgcgca acgttgttgc 7920 cattgctaca ggcatcgtgg tgtcacgctc gtcgtttggt atggcttcat tcagctccgg 7980 ttcccaacga tcaaggcgag ttacatgatc ccccatgttg tgcaaaaaag cggttagctc 8040 cttcggtcct ccgatcgttg tcagaagtaa gttggccgca gtgttatcac tcatggttat 8100 ggcagcactg cataattctc ttactgtcat gccatccgta agatgctttt ctgtgactgg 8160 tgagtactca accaagtcat tctgagaata gtgtatgcgg cgaccgagtt gctcttgccc 8220 ggcgtcaata cgggataata ccgcgccaca tagca 8255 <210> 64 <211> 6746 <212> DNA <213> artificial sequence <220> <223> vector pUC_AAVS1_p-Resp-(PU.1) <400> 64 tcgcgcgttt cggtgatgac ggtgaaaacc tctgacacat gcagctcccg gagacggtca 60 cagcttgtct gtaagcggat gccgggagca gacaagcccg tcagggcgcg tcagcgggtg 120 ttggcgggtg tcggggctgg cttaactatg cggcatcaga gcagattgta ctgagagtgc 180 accatatgcg gtgtgaaata ccgcacagat gcgtaaggag aaaataccgc atcaggcgcc 240 attcgccatt caggctgcgc aactgttggg aagggcgatc ggtgcgggcc tcttcgctat 300 tacgccagct ggcgaaaggg ggatgtgctg caaggcgatt aagttgggta acgccagggt 360 tttcccagtc acgacgttgt aaaacgacgg ccagtgaatt gtgctttctc tgaccagcat 420 tctctcccct gggcctgtgc cgctttctgt ctgtagcttg tggcctgggt cacctctacg 480 gctggcccag atccttccct gccgcctcct tcaggttccg tcttcctcca ctccctcttc 540 cccttgctct ctgctgtgtt gctgcccaag gatgctcttt ccggagcact tccttctcgg 600 cgctgcacca cgtgatgtcc tctgagcgga tcctccccgt gtctgggtcc tctccgggca 660 tctctcctcc ctcacccaac cccatgccgt cttcactcgc tgggttccct tttccttctc 720 cttctggggc ctgtgccatc tctcgtttct taggatggcc ttctccgacg gatgtctccc 780 ttgcgtcccg cctccccttc ttgtaggcct gcatcatcac cgtttttctg gacaacccca 840 aagtaccccg tctccctggc tttagccacc tctccatcct cttgctttct ttgcctggac 900 accccgttct cctgtggatt cgggtcacct ctcactcctt tcatttgggc agctccccta 960 ccccccttac ctctctagtc tgtgctagct cttccagccc cctgtcatgg catcttccag 1020 gggtccgaga gctcagctag tcttcttcct ccaacccggg cccctatgtc cacttcagga 1080 cagcatgttt gctgcctcca gggatcctgt gtccccgagc tgggaccacc ttatattccc 1140 agggccggtt aatgtggctc tggttctggg tacttttatc tgtcccctcc accccacagt 1200 ggggcaagct tctgacctct tctcttcctc ccacagggcc tcgagagatc tggcagcgga 1260 gagggcagag gaagtcttct aacatgcggt gacgtggagg agaatcccgg ccctaggctc 1320 gagatgaccg agtacaagcc cacggtgcgc ctcgccaccc gcgacgacgt ccccagggcc 1380 gtacgcaccc tcgccgccgc gttcgccgac taccccgcca cgcgccacac cgtcgatccg 1440 gaccgccaca tcgagcgggt caccgagctg caagaactct tcctcacgcg cgtcgggctc 1500 gacatcggca aggtgtgggt cgcggacgac ggcgccgcgg tggcggtctg gaccacgccg 1560 gagagcgtcg aagcgggggc ggtgttcgcc gagatcggcc cgcgcatggc cgagttgagc 1620 ggttcccggc tggccgcgca gcaacagatg gaaggcctcc tggcgccgca ccggcccaag 1680 gagcccgcgt ggttcctggc caccgtcggc gtctcgcccg accaccaggg caagggtctg 1740 ggcagcgccg tcgtgctccc cggagtggag gcggccgagc gcgccggggt gcccgccttc 1800 ctggagacct ccgcgccccg caacctcccc ttctacgagc ggctcggctt caccgtcacc 1860 gccgacgtcg aggtgcccga aggaccgcgc acctggtgca tgacccgcaa gcccggtgcc 1920 tgatctagag ggcccgttta aacccgctga tcagcctcga ctgtgccttc tagttgccag 1980 ccatctgttg tttgcccctc ccccgtgcct tccttgaccc tggaaggtgc cactcccact 2040 gtcctttcct aataaaatga ggaaattgca tcgcattgtc tgagtaggtg tcattctatt 2100 ctggggggtg gggtggggca ggacagcaag ggggaggatt gggaagacaa tagcaggcat 2160 gctggggatg cggtgggctc tatggtcact cgagtttact ccctatcagt gatagagaac 2220 gtatgaagag tttactccct atcagtgata gagaacgtat gcagacttta ctccctatca 2280 gtgatagaga acgtataagg agtttactcc ctatcagtga tagagaacgt atgaccagtt 2340 tactccctat cagtgataga gaacgtatct acagtttact ccctatcagt gatagagaac 2400 gtatatccag tttactccct atcagtgata gagaacgtat gtcgaggtag gcgtgtacgg 2460 tgggcgccta taaaagcaga gctcgtttag tgaaccgtca gatcgcctgg agcaattcca 2520 caacactttt gtcttatact tactagtgcc accatgttac aggcgtgcaa aatggaaggg 2580 tttcccctcg tcccccctcc atcagaagac ctggtgccct atgacacgga tctataccaa 2640 cgccaaacgc acgagtatta cccctatctc agcagtgatg gggagagcca tagcgaccat 2700 tactgggact tccaccccca ccacgtgcac agcgagttcg agagcttcgc cgagaacaac 2760 ttcacggagc tccagagcgt gcagcccccg cagctgcagc agctctaccg ccacatggag 2820 ctggagcaga tgcacgtcct cgataccccc atggtgccac cccatcccag tcttggccac 2880 caggtctcct acctgccccg gatgtgcctc cagtacccat ccctgtcccc agcccagccc 2940 agctcagatg aggaggaggg cgagcggcag agccccccac tggaggtgtc tgacggcgag 3000 gcggatggcc tggagcccgg gcctgggctc ctgcctgggg agacaggcag caagaagaag 3060 atccgcctgt accagttcct gttggacctg ctccgcagcg gcgacatgaa ggacagcatc 3120 tggtgggtgg acaaggacaa gggcaccttc cagttctcgt ccaagcacaa ggaggcgctg 3180 gcgcaccgct ggggcatcca gaagggcaac cgcaagaaga tgacctacca gaagatggcg 3240 cgcgcgctgc gcaactacgg caagacgggc gaggtcaaga aggtgaagaa gaagctcacc 3300 taccagttca gcggcgaagt gctgggccgc gggggcctgg ccgagcggcg ccacccgccc 3360 cactgagaat tcgagctcgg tacccgggga tcctctagtc agctgacgcg tgctagcgcg 3420 gccgcatcga taagcttgtc gacgatatct ctagaggatc ataatcagcc ataccacatt 3480 tgtagaggtt ttacttgctt taaaaaacct cccacacctc cccctgaacc tgaaacataa 3540 aatgaatgca attgttgttg ttaacttgtt tattgcagct tataatggtt acaaataaag 3600 caatagcatc acaaatttca caaataaagc atttttttca ctgccttgac agtactctta 3660 agtcgactta ctagggacag gattggtgac agaaaagccc catccttagg cctcctcctt 3720 cctagtctcc tgatattggg tctaaccccc acctcctgtt aggcagattc cttatctggt 3780 gacacacccc catttcctgg agccatctct ctccttgcca gaacctctaa ggtttgctta 3840 cgatggagcc agagaggatc ctgggaggga gagcttggca gggggtggga gggaaggggg 3900 ggatgcgtga cctgcccggt tctcagtggc caccctgcgc taccctctcc cagaacctga 3960 gctgctctga cgcggctgtc tggtgcgttt cactgatcct ggtgctgcag cttccttaca 4020 cttcccaaga ggagaagcag tttggaaaaa caaaatcaga ataagttggt cctgagttct 4080 aactttggct cttcaccttt ctagtcccca atttatattg ttcctccgtg cgtcagtttt 4140 acctgtgaga taaggccagt agccagcccc gtcctggcag ggctgtggtg aggagggggg 4200 tgtccgtgtg gaaaactccc tttgtgagaa tggtgcgtcc taggtgttca ccaggtcgtg 4260 gccgcctcta ctccctttct ctttctccat ccttctttcc ttaaagagtc cccagtgcta 4320 tctgggacat attcctccgc ccagagcagg gtcccgcttc cctaaggccc tgctctgggc 4380 ttctgggttt gagtccttgg caagcccagg agaggcgctc aggcttccct gtcccccttc 4440 ctcgtccacc atctcatgcc cctggctctc ctgccccttc cctacagggg ttcctggctc 4500 tgctctaagc ttggcgtaat catggtcata gctgtttcct gtgtgaaatt gttatccgct 4560 cacaattcca cacaacatac gagccggaag cataaagtgt aaagcctggg gtgcctaatg 4620 agtgagctaa ctcacattaa ttgcgttgcg ctcactgccc gctttccagt cgggaaacct 4680 gtcgtgccag ctgcattaat gaatcggcca acgcgcgggg agaggcggtt tgcgtattgg 4740 gcgctcttcc gcttcctcgc tcactgactc gctgcgctcg gtcgttcggc tgcggcgagc 4800 ggtatcagct cactcaaagg cggtaatacg gttatccaca gaatcagggg ataacgcagg 4860 aaagaacatg tgagcaaaag gccagcaaaa ggccaggaac cgtaaaaagg ccgcgttgct 4920 ggcgtttttc cataggctcc gcccccctga cgagcatcac aaaaatcgac gctcaagtca 4980 gaggtggcga aacccgacag gactataaag ataccaggcg tttccccctg gaagctccct 5040 cgtgcgctct cctgttccga ccctgccgct taccggatac ctgtccgcct ttctcccttc 5100 gggaagcgtg gcgctttctc atagctcacg ctgtaggtat ctcagttcgg tgtaggtcgt 5160 tcgctccaag ctgggctgtg tgcacgaacc ccccgttcag cccgaccgct gcgccttatc 5220 cggtaactat cgtcttgagt ccaacccggt aagacacgac ttatcgccac tggcagcagc 5280 cactggtaac aggattagca gagcgaggta tgtaggcggt gctacagagt tcttgaagtg 5340 gtggcctaac tacggctaca ctagaagaac agtatttggt atctgcgctc tgctgaagcc 5400 agttaccttc ggaaaaagag ttggtagctc ttgatccggc aaacaaacca ccgctggtag 5460 cggtggtttt tttgtttgca agcagcagat tacgcgcaga aaaaaaggat ctcaagaaga 5520 tcctttgatc ttttctacgg ggtctgacgc tcagtggaac gaaaactcac gttaagggat 5580 tttggtcatg agattatcaa aaaggatctt cacctagatc cttttaaatt aaaaatgaag 5640 ttttaaatca atctaaagta tatatgagta aacttggtct gacagttacc aatgcttaat 5700 cagtgaggca cctatctcag cgatctgtct atttcgttca tccatagttg cctgactccc 5760 cgtcgtgtag ataactacga tacgggaggg cttaccatct ggccccagtg ctgcaatgat 5820 accgcgagac ccacgctcac cggctccaga tttatcagca ataaaccagc cagccggaag 5880 ggccgagcgc agaagtggtc ctgcaacttt atccgcctcc atccagtcta ttaattgttg 5940 ccgggaagct agagtaagta gttcgccagt taatagtttg cgcaacgttg ttgccattgc 6000 tacaggcatc gtggtgtcac gctcgtcgtt tggtatggct tcattcagct ccggttccca 6060 acgatcaagg cgagttacat gatcccccat gttgtgcaaa aaagcggtta gctccttcgg 6120 tcctccgatc gttgtcagaa gtaagttggc cgcagtgtta tcactcatgg ttatggcagc 6180 actgcataat tctcttactg tcatgccatc cgtaagatgc ttttctgtga ctggtgagta 6240 ctcaaccaag tcattctgag aatagtgtat gcggcgaccg agttgctctt gcccggcgtc 6300 aatacgggat aataccgcgc cacatagcag aactttaaaa gtgctcatca ttggaaaacg 6360 ttcttcgggg cgaaaactct caaggatctt accgctgttg agatccagtt cgatgtaacc 6420 cactcgtgca cccaactgat cttcagcatc ttttactttc accagcgttt ctgggtgagc 6480 aaaaacagga aggcaaaatg ccgcaaaaaa gggaataagg gcgacacgga aatgttgaat 6540 actcatactc ttcctttttc aatattattg aagcatttat cagggttatt gtctcatgag 6600 cggatacata tttgaatgta tttagaaaaa taaacaaata ggggttccgc gcacatttcc 6660 ccgaaaagtg ccacctgacg tctaagaaac cattattatc atgacattaa cctataaaaa 6720 taggcgtatc acgaggccct ttcgtc 6746 <210> 65 <211> 10781 <212> DNA <213> artificial sequence <220> <223> vector pUC_AAVS1_p-Resp-(PU.1-SALL1) <400> 65 gaactttaaa agtgctcatc attggaaaac gttcttcggg gcgaaaactc tcaaggatct 60 taccgctgtt gagatccagt tcgatgtaac ccactcgtgc acccaactga tcttcagcat 120 cttttacttt caccagcgtt tctgggtgag caaaaacagg aaggcaaaat gccgcaaaaa 180 agggaataag ggcgacacgg aaatgttgaa tactcatact cttccttttt caatattatt 240 gaagcattta tcagggttat tgtctcatga gcggatacat atttgaatgt atttagaaaa 300 ataaacaaat aggggttccg cgcacatttc cccgaaaagt gccacctgac gtctaagaaa 360 ccattattat catgacatta acctataaaa ataggcgtat cacgaggccc tttcgtctcg 420 cgcgtttcgg tgatgacggt gaaaacctct gacacatgca gctcccggag acggtcacag 480 cttgtctgta agcggatgcc gggagcagac aagcccgtca gggcgcgtca gcgggtgttg 540 gcgggtgtcg gggctggctt aactatgcgg catcagagca gattgtactg agagtgcacc 600 atatgcggtg tgaaataccg cacagatgcg taaggagaaa ataccgcatc aggcgccatt 660 cgccattcag gctgcgcaac tgttgggaag ggcgatcggt gcgggcctct tcgctattac 720 gccagctggc gaaaggggga tgtgctgcaa ggcgattaag ttgggtaacg ccagggtttt 780 cccagtcacg acgttgtaaa acgacggcca gtgaattgtg ctttctctga ccagcattct 840 ctcccctggg cctgtgccgc tttctgtctg tagcttgtgg cctgggtcac ctctacggct 900 ggcccagatc cttccctgcc gcctccttca ggttccgtct tcctccactc cctcttcccc 960 ttgctctctg ctgtgttgct gcccaaggat gctctttccg gagcacttcc ttctcggcgc 1020 tgcaccacgt gatgtcctct gagcggatcc tccccgtgtc tgggtcctct ccgggcatct 1080 ctcctccctc acccaacccc atgccgtctt cactcgctgg gttccctttt ccttctcctt 1140 ctggggcctg tgccatctct cgtttcttag gatggccttc tccgacggat gtctcccttg 1200 cgtcccgcct ccccttcttg taggcctgca tcatcaccgt ttttctggac aaccccaaag 1260 taccccgtct ccctggcttt agccacctct ccatcctctt gctttctttg cctggacacc 1320 ccgttctcct gtggattcgg gtcacctctc actcctttca tttgggcagc tcccctaccc 1380 cccttacctc tctagtctgt gctagctctt ccagccccct gtcatggcat cttccagggg 1440 tccgagagct cagctagtct tcttcctcca acccgggccc ctatgtccac ttcaggacag 1500 catgtttgct gcctccaggg atcctgtgtc cccgagctgg gaccacctta tattcccagg 1560 gccggttaat gtggctctgg ttctgggtac ttttatctgt cccctccacc ccacagtggg 1620 gcaagcttct gacctcttct cttcctccca cagggcctcg agagatctgg cagcggagag 1680 ggcagaggaa gtcttctaac atgcggtgac gtggaggaga atcccggccc taggctcgag 1740 atgaccgagt acaagcccac ggtgcgcctc gccacccgcg acgacgtccc cagggccgta 1800 cgcaccctcg ccgccgcgtt cgccgactac cccgccacgc gccacaccgt cgatccggac 1860 cgccacatcg agcgggtcac cgagctgcaa gaactcttcc tcacgcgcgt cgggctcgac 1920 atcggcaagg tgtgggtcgc ggacgacggc gccgcggtgg cggtctggac cacgccggag 1980 agcgtcgaag cgggggcggt gttcgccgag atcggcccgc gcatggccga gttgagcggt 2040 tcccggctgg ccgcgcagca acagatggaa ggcctcctgg cgccgcaccg gcccaaggag 2100 cccgcgtggt tcctggccac cgtcggcgtc tcgcccgacc accagggcaa gggtctgggc 2160 agcgccgtcg tgctccccgg agtggaggcg gccgagcgcg ccggggtgcc cgccttcctg 2220 gagacctccg cgccccgcaa cctccccttc tacgagcggc tcggcttcac cgtcaccgcc 2280 gacgtcgagg tgcccgaagg accgcgcacc tggtgcatga cccgcaagcc cggtgcctga 2340 tctagagggc ccgtttaaac ccgctgatca gcctcgactg tgccttctag ttgccagcca 2400 tctgttgttt gcccctcccc cgtgccttcc ttgaccctgg aaggtgccac tcccactgtc 2460 ctttcctaat aaaatgagga aattgcatcg cattgtctga gtaggtgtca ttctattctg 2520 gggggtgggg tggggcagga cagcaagggg gaggattggg aagacaatag caggcatgct 2580 ggggatgcgg tgggctctat ggtcactcga gtttactccc tatcagtgat agagaacgta 2640 tgaagagttt actccctatc agtgatagag aacgtatgca gactttactc cctatcagtg 2700 atagagaacg tataaggagt ttactcccta tcagtgatag agaacgtatg accagtttac 2760 tccctatcag tgatagagaa cgtatctaca gtttactccc tatcagtgat agagaacgta 2820 tatccagttt actccctatc agtgatagag aacgtatgtc gaggtaggcg tgtacggtgg 2880 gcgcctataa aagcagagct cgtttagtga accgtcagat cgcctggagc aattccacaa 2940 cacttttgtc ttatacttac tagtgccacc atgttacagg cgtgcaaaat ggaagggttt 3000 cccctcgtcc cccctccatc agaagacctg gtgccctatg acacggatct ataccaacgc 3060 caaacgcacg agtattaccc ctatctcagc agtgatgggg agagccatag cgaccattac 3120 tgggacttcc acccccacca cgtgcacagc gagttcgaga gcttcgccga gaacaacttc 3180 acggagctcc agagcgtgca gcccccgcag ctgcagcagc tctaccgcca catggagctg 3240 gagcagatgc acgtcctcga tacccccatg gtgccacccc atcccagtct tggccaccag 3300 gtctcctacc tgccccggat gtgcctccag tacccatccc tgtccccagc ccagcccagc 3360 tcagatgagg aggagggcga gcggcagagc cccccactgg aggtgtctga cggcgaggcg 3420 gatggcctgg agcccgggcc tgggctcctg cctggggaga caggcagcaa gaagaagatc 3480 cgcctgtacc agttcctgtt ggacctgctc cgcagcggcg acatgaagga cagcatctgg 3540 tgggtggaca aggacaaggg caccttccag ttctcgtcca agcacaagga ggcgctggcg 3600 caccgctggg gcatccagaa gggcaaccgc aagaagatga cctaccagaa gatggcgcgc 3660 gcgctgcgca actacggcaa gacgggcgag gtcaagaagg tgaagaagaa gctcacctac 3720 cagttcagcg gcgaagtgct gggccgcggg ggcctggccg agcggcgcca cccgccccac 3780 ggatcgggag agggcagggg aagtcttcta acatgcgggg acgtggagga aaatcccggc 3840 cccatgtcgc ggaggaagca agcgaagcct caacatttcc aatccgaccc cgaagtggcc 3900 tcgctccccc ggcgagatgg agacacagaa aagggtcaac cgagtcgccc tactaagagc 3960 aaggatgccc acgtctgtgg ccggtgctgt gccgagttct ttgaattatc agatcttctg 4020 ctccacaaga agaactgtac taaaaatcaa ttagttttaa tcgtaaatga aaatccagcc 4080 tccccacccg aaaccttctc ccccagcccc cctcctgata atcctgatga acaaatgaat 4140 gacacagtta acaaaacaga tcaagtggac tgcagcgacc tttcagaaca caacggactt 4200 gacagggaag agtccatgga ggtggaggcc ccggttgcta acaaaagcgg cagcggcact 4260 tccagcggca gccacagcag taccgcccca agcagcagca gcagcagcag cagcagcagc 4320 ggcggcggcg gcagctcctc cacaggtacc tcagcgatca caacctctct acctcaactc 4380 ggggacctga caacactggg caacttctcc gtaatcaaca gcaacgtcat catcgagaac 4440 ctccagagca ccaaggtggc ggtggcccag ttctcccagg aagcgaggtg cggcggggcc 4500 tctgggggca agctggccgt cccagccctc atggaacaac tcctagctct gcagcagcag 4560 cagatccacc agctgcaatt gatcgaacag attcgtcacc aaatattgct gttggcttct 4620 cagaatgcag acttgccaac atcttctagt ccttctcaag gtactttacg aacatctgcc 4680 aaccccttgt ccacgctaag ttcccattta tctcagcagc tggcagcagc agctggattg 4740 gcacagagcc tcgccagcca atctgccagc attagtggtg tgaaacagct acccccaatc 4800 cagctacctc agagcagttc tggcaacacc atcattccat ccaacagcgg ctcttctccc 4860 aatatgaaca tattggcagc ggcagttacc accccgtcct ctgaaaaagt ggcttcaagt 4920 gctggggcct cccatgtcag caacccagcg gtctcatcat cgtcctcacc agcttttgca 4980 ataagcagtt tattaagtcc tgcgtctaat ccacttctac ctcagcaagc ctccgctaac 5040 tcggttttcc ccagcccttt gcccaacatc ggaacaactg cagaggattt aaactccttg 5100 tctgccttgg cccagcaaag aaaaagcaag ccaccaaatg tcactgcctt tgaagcgaaa 5160 agtacttccg atgaggcatt cttcaaacac aagtgcaggt tctgcgcgaa ggtctttggg 5220 agtgacagtg ccttgcagat ccacttgcgt tcccataccg gagagaggcc attcaagtgc 5280 aacatctgcg ggaacaggtt ctccaccaag gggaatctga aagtccactt tcagcgccac 5340 aaagagaaat accctcatat ccagatgaac ccctatcctg tgcctgagca tttggacaat 5400 atccccacga gtactggcat cccatatggc atgtccatcc ctccagagaa gccagtcacc 5460 agctggctag acaccaaacc agtcctgcct actctgacca cttcagtcgg cctgccgttg 5520 cccccaaccc tcccaagcct catacccttc atcaagacgg aagagccagc ccccatcccc 5580 atcagccatt ctgccaccag ccccccaggc tcagtcaaaa gtgactccgg gggccctgag 5640 tcagccacaa gaaacctagg tgggctccca gaggaagccg aagggtccac tctgccaccc 5700 tctggtggca aaagcgaaga gagtggcatg gtcaccaact cagtcccgac ggcgagcagt 5760 agcgtcctga gctccccagc ggcagactgc ggccccgcgg gcagtgccac caccttcacc 5820 aaccctttgt tgccgctcat gtccgagcag ttcaaggcca agtttccttt tgggggactc 5880 ctggactcag ctcaggcatc agagacgtcc aagcttcagc aactggtaga aaacattgac 5940 aagaaggcca ctgaccccaa tgagtgcatc atctgccacc gggttctcag ctgccagagc 6000 gccttgaaaa tgcactacag gacacacact ggggagaggc cctttaagtg taagatctgt 6060 ggccgggctt tcaccacgaa agggaatctt aaaacccact acagtgtcca tcgtgctatg 6120 cccccgctca gagtccagca ttcctgcccc atctgccaga agaagttcac gaacgctgtg 6180 gtcctgcagc agcacatccg aatgcatatg ggaggccaga tccccaacac cccagtcccc 6240 gacagctact ctgagtccat ggagtctgac acaggttcct ttgatgagaa aaattttgat 6300 gacctagaca acttctctga tgaaaacatg gaagactgtc ctgagggcag catccctgat 6360 acacctaagt ctgcagacgc ctcccaagac agcttatcct cttcgccttt gcccctcgag 6420 atgtcgagca tcgctgcttt ggaaaatcag atgaagatga tcaatgctgg cctggcagag 6480 cagctacagg ccagcctgaa gtcagtggag aatgggtcca tcgaggggga tgtcctgacc 6540 aatgattcat cctcagtggg tggtgacatg gaaagccaaa gtgctggcag cccagccatc 6600 tcagagtcta cctcttccat gcaggctctg tccccgtcca acagcacgca ggagttccac 6660 aagtcaccca gcattgagga gaaaccacag agagcggtcc caagcgagtt tgccaatggt 6720 ttgtctccca ccccagtgaa tggtggggct ttggatttga catctagtca cgcagagaaa 6780 atcatcaaag aagattcttt ggggatcctc ttccctttta gagaccgggg taaatttaaa 6840 aacactgctt gtgacatttg tggcaaaaca tttgcttgtc agagtgcctt ggacattcac 6900 tatagaagtc ataccaaaga gagaccattt atttgcacag tttgcaatcg tggcttttcc 6960 acaaagggta atttgaagca gcacatgttg acacatcaga tgcgagatct gccatcccag 7020 ctctttgagc ccagttccaa ccttggcccc aatcagaact cagcggtgat tcccgccaac 7080 tcgttgtcat ctctcatcaa gacagaggtc aacggcttcg tgcatgtttc tcctcaggac 7140 agtaaggaca cccccaccag tcacgtcccg tctgggcctc tgtcttcctc tgccacatcc 7200 ccagttctgc tccctgctct gcccaggaga actcccaagc agcactactg caacacatgt 7260 ggcaaaacct tctcctcatc gagtgccctg cagattcacg agagaactca cactggagag 7320 aaaccctttg cttgcactat ttgtggaaga gctttcacga ctaaaggcaa tcttaaggta 7380 cacatgggca ctcacatgtg gaatagcacc cctgcacgac ggggtcggcg gctctctgtg 7440 gatggcccca tgacatttct aggaggcaat cccgtcaagt tcccagaaat gttccagaag 7500 gatttggcgg caagatcagg aagtggggat ccttccagct tctggaatca gtatgcagca 7560 gcgctctcca acgggctggc gatgaaggcc aacgagatct ccgtcattca gaacggtggc 7620 atccctccaa ttcctggaag cctcggcagt gggaacagct cacctgttag tgggctgacg 7680 ggaaacctgg agaggctcca gaactcagag cccaatgctc ccctggccgg cctggagaaa 7740 atggcaagca gtgagaacgg aaccaacttc cgcttcaccc gcttcgtgga ggacagcaag 7800 gagatcgtca cgagttaaga attcgagctc ggtacccggg gatcctctag tcagctgacg 7860 cgtgctagcg cggccgcatc gataagcttg tcgacgatat ctctagagga tcataatcag 7920 ccataccaca tttgtagagg ttttacttgc tttaaaaaac ctcccacacc tccccctgaa 7980 cctgaaacat aaaatgaatg caattgttgt tgttaacttg tttattgcag cttataatgg 8040 ttacaaataa agcaatagca tcacaaattt cacaaataaa gcattttttt cactgccttg 8100 acagtactct taagtcgact tactagggac aggattggtg acagaaaagc cccatcctta 8160 ggcctcctcc ttcctagtct cctgatattg ggtctaaccc ccacctcctg ttaggcagat 8220 tccttatctg gtgacacacc cccatttcct ggagccatct ctctccttgc cagaacctct 8280 aaggtttgct tacgatggag ccagagagga tcctgggagg gagagcttgg cagggggtgg 8340 gagggaaggg ggggatgcgt gacctgcccg gttctcagtg gccaccctgc gctaccctct 8400 cccagaacct gagctgctct gacgcggctg tctggtgcgt ttcactgatc ctggtgctgc 8460 agcttcctta cacttcccaa gaggagaagc agtttggaaa aacaaaatca gaataagttg 8520 gtcctgagtt ctaactttgg ctcttcacct ttctagtccc caatttatat tgttcctccg 8580 tgcgtcagtt ttacctgtga gataaggcca gtagccagcc ccgtcctggc agggctgtgg 8640 tgaggagggg ggtgtccgtg tggaaaactc cctttgtgag aatggtgcgt cctaggtgtt 8700 caccaggtcg tggccgcctc tactcccttt ctctttctcc atccttcttt ccttaaagag 8760 tccccagtgc tatctgggac atattcctcc gcccagagca gggtcccgct tccctaaggc 8820 cctgctctgg gcttctgggt ttgagtcctt ggcaagccca ggagaggcgc tcaggcttcc 8880 ctgtccccct tcctcgtcca ccatctcatg cccctggctc tcctgcccct tccctacagg 8940 ggttcctggc tctgctctaa gcttggcgta atcatggtca tagctgtttc ctgtgtgaaa 9000 ttgttatccg ctcacaattc cacacaacat acgagccgga agcataaagt gtaaagcctg 9060 gggtgcctaa tgagtgagct aactcacatt aattgcgttg cgctcactgc ccgctttcca 9120 gtcgggaaac ctgtcgtgcc agctgcatta atgaatcggc caacgcgcgg ggagaggcgg 9180 tttgcgtatt gggcgctctt ccgcttcctc gctcactgac tcgctgcgct cggtcgttcg 9240 gctgcggcga gcggtatcag ctcactcaaa ggcggtaata cggttatcca cagaatcagg 9300 ggataacgca ggaaagaaca tgtgagcaaa aggccagcaa aaggccagga accgtaaaaa 9360 ggccgcgttg ctggcgtttt tccataggct ccgcccccct gacgagcatc acaaaaatcg 9420 acgctcaagt cagaggtggc gaaacccgac aggactataa agataccagg cgtttccccc 9480 tggaagctcc ctcgtgcgct ctcctgttcc gaccctgccg cttaccggat acctgtccgc 9540 ctttctccct tcgggaagcg tggcgctttc tcatagctca cgctgtaggt atctcagttc 9600 ggtgtaggtc gttcgctcca agctgggctg tgtgcacgaa ccccccgttc agcccgaccg 9660 ctgcgcctta tccggtaact atcgtcttga gtccaacccg gtaagacacg acttatcgcc 9720 actggcagca gccactggta acaggattag cagagcgagg tatgtaggcg gtgctacaga 9780 gttcttgaag tggtggccta actacggcta cactagaaga acagtatttg gtatctgcgc 9840 tctgctgaag ccagttacct tcggaaaaag agttggtagc tcttgatccg gcaaacaaac 9900 caccgctggt agcggtggtt tttttgtttg caagcagcag attacgcgca gaaaaaaagg 9960 atctcaagaa gatcctttga tcttttctac ggggtctgac gctcagtgga acgaaaactc 10020 acgttaaggg attttggtca tgagattatc aaaaaggatc ttcacctaga tccttttaaa 10080 ttaaaaatga agttttaaat caatctaaag tatatatgag taaacttggt ctgacagtta 10140 ccaatgctta atcagtgagg cacctatctc agcgatctgt ctatttcgtt catccatagt 10200 tgcctgactc cccgtcgtgt agataactac gatacgggag ggcttaccat ctggccccag 10260 tgctgcaatg ataccgcgag acccacgctc accggctcca gatttatcag caataaacca 10320 gccagccgga agggccgagc gcagaagtgg tcctgcaact ttatccgcct ccatccagtc 10380 tattaattgt tgccgggaag ctagagtaag tagttcgcca gttaatagtt tgcgcaacgt 10440 tgttgccatt gctacaggca tcgtggtgtc acgctcgtcg tttggtatgg cttcattcag 10500 ctccggttcc caacgatcaa ggcgagttac atgatccccc atgttgtgca aaaaagcggt 10560 tagctccttc ggtcctccga tcgttgtcag aagtaagttg gccgcagtgt tatcactcat 10620 ggttatggca gcactgcata attctcttac tgtcatgcca tccgtaagat gcttttctgt 10680 gactggtgag tactcaacca agtcattctg agaatagtgt atgcggcgac cgagttgctc 10740 ttgcccggcg tcaatacggg ataataccgc gccacatagc a 10781 <210> 66 <211> 8508 <212> DNA <213> artificial sequence <220> <223> ROSA26-guide A_Cas9n <400> 66 gagggcctat ttcccatgat tccttcatat ttgcatatac gatacaaggc tgttagagag 60 ataattggaa ttaatttgac tgtaaacaca aagatattag tacaaaatac gtgacgtaga 120 aagtaataat ttcttgggta gtttgcagtt ttaaaattat gttttaaaat ggactatcat 180 atgcttaccg taacttgaaa gtatttcgat ttcttggctt tatatatctt gtggaaagga 240 cgaaacaccg tcgagtcgct tctcgattag ttttagagct agaaatagca agttaaaata 300 aggctagtcc gttatcaact tgaaaaagtg gcaccgagtc ggtgcttttt tgttttagag 360 ctagaaatag caagttaaaa taaggctagt ccgtttttag cgcgtgcgcc aattctgcag 420 acaaatggct ctagaggtac ccgttacata acttacggta aatggcccgc ctggctgacc 480 gcccaacgac ccccgcccat tgacgtcaat agtaacgcca atagggactt tccattgacg 540 tcaatgggtg gagtatttac ggtaaactgc ccacttggca gtacatcaag tgtatcatat 600 gccaagtacg ccccctattg acgtcaatga cggtaaatgg cccgcctggc attgtgccca 660 gtacatgacc ttatgggact ttcctacttg gcagtacatc tacgtattag tcatcgctat 720 taccatggtc gaggtgagcc ccacgttctg cttcactctc cccatctccc ccccctcccc 780 acccccaatt ttgtatttat ttatttttta attattttgt gcagcgatgg gggcgggggg 840 gggggggggg cgcgcgccag gcggggcggg gcggggcgag gggcggggcg gggcgaggcg 900 gagaggtgcg gcggcagcca atcagagcgg cgcgctccga aagtttcctt ttatggcgag 960 gcggcggcgg cggcggccct ataaaaagcg aagcgcgcgg cgggcgggag tcgctgcgac 1020 gctgccttcg ccccgtgccc cgctccgccg ccgcctcgcg ccgcccgccc cggctctgac 1080 tgaccgcgtt actcccacag gtgagcgggc gggacggccc ttctcctccg ggctgtaatt 1140 agctgagcaa gaggtaaggg tttaagggat ggttggttgg tggggtatta atgtttaatt 1200 acctggagca cctgcctgaa atcacttttt ttcaggttgg accggtgcca ccatggacta 1260 taaggaccac gacggagact acaaggatca tgatattgat tacaaagacg atgacgataa 1320 gatggcccca aagaagaagc ggaaggtcgg tatccacgga gtcccagcag ccgacaagaa 1380 gtacagcatc ggcctggcca tcggcaccaa ctctgtgggc tgggccgtga tcaccgacga 1440 gtacaaggtg cccagcaaga aattcaaggt gctgggcaac accgaccggc acagcatcaa 1500 gaagaacctg atcggagccc tgctgttcga cagcggcgaa acagccgagg ccacccggct 1560 gaagagaacc gccagaagaa gatacaccag acggaagaac cggatctgct atctgcaaga 1620 gatcttcagc aacgagatgg ccaaggtgga cgacagcttc ttccacagac tggaagagtc 1680 cttcctggtg gaagaggata agaagcacga gcggcacccc atcttcggca acatcgtgga 1740 cgaggtggcc taccacgaga agtaccccac catctaccac ctgagaaaga aactggtgga 1800 cagcaccgac aaggccgacc tgcggctgat ctatctggcc ctggcccaca tgatcaagtt 1860 ccggggccac ttcctgatcg agggcgacct gaaccccgac aacagcgacg tggacaagct 1920 gttcatccag ctggtgcaga cctacaacca gctgttcgag gaaaacccca tcaacgccag 1980 cggcgtggac gccaaggcca tcctgtctgc cagactgagc aagagcagac ggctggaaaa 2040 tctgatcgcc cagctgcccg gcgagaagaa gaatggcctg ttcggcaacc tgattgccct 2100 gagcctgggc ctgaccccca acttcaagag caacttcgac ctggccgagg atgccaaact 2160 gcagctgagc aaggacacct acgacgacga cctggacaac ctgctggccc agatcggcga 2220 ccagtacgcc gacctgtttc tggccgccaa gaacctgtcc gacgccatcc tgctgagcga 2280 catcctgaga gtgaacaccg agatcaccaa ggcccccctg agcgcctcta tgatcaagag 2340 atacgacgag caccaccagg acctgaccct gctgaaagct ctcgtgcggc agcagctgcc 2400 tgagaagtac aaagagattt tcttcgacca gagcaagaac ggctacgccg gctacattga 2460 cggcggagcc agccaggaag agttctacaa gttcatcaag cccatcctgg aaaagatgga 2520 cggcaccgag gaactgctcg tgaagctgaa cagagaggac ctgctgcgga agcagcggac 2580 cttcgacaac ggcagcatcc cccaccagat ccacctggga gagctgcacg ccattctgcg 2640 gcggcaggaa gatttttacc cattcctgaa ggacaaccgg gaaaagatcg agaagatcct 2700 gaccttccgc atcccctact acgtgggccc tctggccagg ggaaacagca gattcgcctg 2760 gatgaccaga aagagcgagg aaaccatcac cccctggaac ttcgaggaag tggtggacaa 2820 gggcgcttcc gcccagagct tcatcgagcg gatgaccaac ttcgataaga acctgcccaa 2880 cgagaaggtg ctgcccaagc acagcctgct gtacgagtac ttcaccgtgt ataacgagct 2940 gaccaaagtg aaatacgtga ccgagggaat gagaaagccc gccttcctga gcggcgagca 3000 gaaaaaggcc atcgtggacc tgctgttcaa gaccaaccgg aaagtgaccg tgaagcagct 3060 gaaagaggac tacttcaaga aaatcgagtg cttcgactcc gtggaaatct ccggcgtgga 3120 agatcggttc aacgcctccc tgggcacata ccacgatctg ctgaaaatta tcaaggacaa 3180 ggacttcctg gacaatgagg aaaacgagga cattctggaa gatatcgtgc tgaccctgac 3240 actgtttgag gacagagaga tgatcgagga acggctgaaa acctatgccc acctgttcga 3300 cgacaaagtg atgaagcagc tgaagcggcg gagatacacc ggctggggca ggctgagccg 3360 gaagctgatc aacggcatcc gggacaagca gtccggcaag acaatcctgg atttcctgaa 3420 gtccgacggc ttcgccaaca gaaacttcat gcagctgatc cacgacgaca gcctgacctt 3480 taaagaggac atccagaaag cccaggtgtc cggccagggc gatagcctgc acgagcacat 3540 tgccaatctg gccggcagcc ccgccattaa gaagggcatc ctgcagacag tgaaggtggt 3600 ggacgagctc gtgaaagtga tgggccggca caagcccgag aacatcgtga tcgaaatggc 3660 cagagagaac cagaccaccc agaagggaca gaagaacagc cgcgagagaa tgaagcggat 3720 cgaagagggc atcaaagagc tgggcagcca gatcctgaaa gaacaccccg tggaaaacac 3780 ccagctgcag aacgagaagc tgtacctgta ctacctgcag aatgggcggg atatgtacgt 3840 ggaccaggaa ctggacatca accggctgtc cgactacgat gtggaccata tcgtgcctca 3900 gagctttctg aaggacgact ccatcgacaa caaggtgctg accagaagcg acaagaaccg 3960 gggcaagagc gacaacgtgc cctccgaaga ggtcgtgaag aagatgaaga actactggcg 4020 gcagctgctg aacgccaagc tgattaccca gagaaagttc gacaatctga ccaaggccga 4080 gagaggcggc ctgagcgaac tggataaggc cggcttcatc aagagacagc tggtggaaac 4140 ccggcagatc acaaagcacg tggcacagat cctggactcc cggatgaaca ctaagtacga 4200 cgagaatgac aagctgatcc gggaagtgaa agtgatcacc ctgaagtcca agctggtgtc 4260 cgatttccgg aaggatttcc agttttacaa agtgcgcgag atcaacaact accaccacgc 4320 ccacgacgcc tacctgaacg ccgtcgtggg aaccgccctg atcaaaaagt accctaagct 4380 ggaaagcgag ttcgtgtacg gcgactacaa ggtgtacgac gtgcggaaga tgatcgccaa 4440 gagcgagcag gaaatcggca aggctaccgc caagtacttc ttctacagca acatcatgaa 4500 ctttttcaag accgagatta ccctggccaa cggcgagatc cggaagcggc ctctgatcga 4560 gacaaacggc gaaaccgggg agatcgtgtg ggataagggc cgggattttg ccaccgtgcg 4620 gaaagtgctg agcatgcccc aagtgaatat cgtgaaaaag accgaggtgc agacaggcgg 4680 cttcagcaaa gagtctatcc tgcccaagag gaacagcgat aagctgatcg ccagaaagaa 4740 ggactgggac cctaagaagt acggcggctt cgacagcccc accgtggcct attctgtgct 4800 ggtggtggcc aaagtggaaa agggcaagtc caagaaactg aagagtgtga aagagctgct 4860 ggggatcacc atcatggaaa gaagcagctt cgagaagaat cccatcgact ttctggaagc 4920 caagggctac aaagaagtga aaaaggacct gatcatcaag ctgcctaagt actccctgtt 4980 cgagctggaa aacggccgga agagaatgct ggcctctgcc ggcgaactgc agaagggaaa 5040 cgaactggcc ctgccctcca aatatgtgaa cttcctgtac ctggccagcc actatgagaa 5100 gctgaagggc tcccccgagg ataatgagca gaaacagctg tttgtggaac agcacaagca 5160 ctacctggac gagatcatcg agcagatcag cgagttctcc aagagagtga tcctggccga 5220 cgctaatctg gacaaagtgc tgtccgccta caacaagcac cgggataagc ccatcagaga 5280 gcaggccgag aatatcatcc acctgtttac cctgaccaat ctgggagccc ctgccgcctt 5340 caagtacttt gacaccacca tcgaccggaa gaggtacacc agcaccaaag aggtgctgga 5400 cgccaccctg atccaccaga gcatcaccgg cctgtacgag acacggatcg acctgtctca 5460 gctgggaggc gacaaaaggc cggcggccac gaaaaaggcc ggccaggcaa aaaagaaaaa 5520 gtaagaattc ctagagctcg ctgatcagcc tcgactgtgc cttctagttg ccagccatct 5580 gttgtttgcc cctcccccgt gccttccttg accctggaag gtgccactcc cactgtcctt 5640 tcctaataaa atgaggaaat tgcatcgcat tgtctgagta ggtgtcattc tattctgggg 5700 ggtggggtgg ggcaggacag caagggggag gattgggaag agaatagcag gcatgctggg 5760 gagcggccgc aggaacccct agtgatggag ttggccactc cctctctgcg cgctcgctcg 5820 ctcactgagg ccgggcgacc aaaggtcgcc cgacgcccgg gctttgcccg ggcggcctca 5880 gtgagcgagc gagcgcgcag ctgcctgcag gggcgcctga tgcggtattt tctccttacg 5940 catctgtgcg gtatttcaca ccgcatacgt caaagcaacc atagtacgcg ccctgtagcg 6000 gcgcattaag cgcggcgggt gtggtggtta cgcgcagcgt gaccgctaca cttgccagcg 6060 ccctagcgcc cgctcctttc gctttcttcc cttcctttct cgccacgttc gccggctttc 6120 cccgtcaagc tctaaatcgg gggctccctt tagggttccg atttagtgct ttacggcacc 6180 tcgaccccaa aaaacttgat ttgggtgatg gttcacgtag tgggccatcg ccctgataga 6240 cggtttttcg ccctttgacg ttggagtcca cgttctttaa tagtggactc ttgttccaaa 6300 ctggaacaac actcaaccct atctcgggct attcttttga tttataaggg attttgccga 6360 tttcggccta ttggttaaaa aatgagctga tttaacaaaa atttaacgcg aattttaaca 6420 aaatattaac gtttacaatt ttatggtgca ctctcagtac aatctgctct gatgccgcat 6480 agttaagcca gccccgacac ccgccaacac ccgctgacgc gccctgacgg gcttgtctgc 6540 tcccggcatc cgcttacaga caagctgtga ccgtctccgg gagctgcatg tgtcagaggt 6600 tttcaccgtc atcaccgaaa cgcgcgagac gaaagggcct cgtgatacgc ctatttttat 6660 aggttaatgt catgataata atggtttctt agacgtcagg tggcactttt cggggaaatg 6720 tgcgcggaac ccctatttgt ttatttttct aaatacattc aaatatgtat ccgctcatga 6780 gacaataacc ctgataaatg cttcaataat attgaaaaag gaagagtatg agtattcaac 6840 atttccgtgt cgcccttatt cccttttttg cggcattttg ccttcctgtt tttgctcacc 6900 cagaaacgct ggtgaaagta aaagatgctg aagatcagtt gggtgcacga gtgggttaca 6960 tcgaactgga tctcaacagc ggtaagatcc ttgagagttt tcgccccgaa gaacgttttc 7020 caatgatgag cacttttaaa gttctgctat gtggcgcggt attatcccgt attgacgccg 7080 ggcaagagca actcggtcgc cgcatacact attctcagaa tgacttggtt gagtactcac 7140 cagtcacaga aaagcatctt acggatggca tgacagtaag agaattatgc agtgctgcca 7200 taaccatgag tgataacact gcggccaact tacttctgac aacgatcgga ggaccgaagg 7260 agctaaccgc ttttttgcac aacatggggg atcatgtaac tcgccttgat cgttgggaac 7320 cggagctgaa tgaagccata ccaaacgacg agcgtgacac cacgatgcct gtagcaatgg 7380 caacaacgtt gcgcaaacta ttaactggcg aactacttac tctagcttcc cggcaacaat 7440 taatagactg gatggaggcg gataaagttg caggaccact tctgcgctcg gcccttccgg 7500 ctggctggtt tattgctgat aaatctggag ccggtgagcg tggaagccgc ggtatcattg 7560 cagcactggg gccagatggt aagccctccc gtatcgtagt tatctacacg acggggagtc 7620 aggcaactat ggatgaacga aatagacaga tcgctgagat aggtgcctca ctgattaagc 7680 attggtaact gtcagaccaa gtttactcat atatacttta gattgattta aaacttcatt 7740 tttaatttaa aaggatctag gtgaagatcc tttttgataa tctcatgacc aaaatccctt 7800 aacgtgagtt ttcgttccac tgagcgtcag accccgtaga aaagatcaaa ggatcttctt 7860 gagatccttt ttttctgcgc gtaatctgct gcttgcaaac aaaaaaacca ccgctaccag 7920 cggtggtttg tttgccggat caagagctac caactctttt tccgaaggta actggcttca 7980 gcagagcgca gataccaaat actgtccttc tagtgtagcc gtagttaggc caccacttca 8040 agaactctgt agcaccgcct acatacctcg ctctgctaat cctgttacca gtggctgctg 8100 ccagtggcga taagtcgtgt cttaccgggt tggactcaag acgatagtta ccggataagg 8160 cgcagcggtc gggctgaacg gggggttcgt gcacacagcc cagcttggag cgaacgacct 8220 acaccgaact gagataccta cagcgtgagc tatgagaaag cgccacgctt cccgaaggga 8280 gaaaggcgga caggtatccg gtaagcggca gggtcggaac aggagagcgc acgagggagc 8340 ttccaggggg aaacgcctgg tatctttata gtcctgtcgg gtttcgccac ctctgacttg 8400 agcgtcgatt tttgtgatgc tcgtcagggg ggcggagcct atggaaaaac gccagcaacg 8460 cggccttttt acggttcctg gccttttgct ggccttttgc tcacatgt 8508 <210> 67 <211> 8508 <212> DNA <213> artificial sequence <220> <223> ROSA26-guide B_Cas9n <400> 67 gagggcctat ttcccatgat tccttcatat ttgcatatac gatacaaggc tgttagagag 60 ataattggaa ttaatttgac tgtaaacaca aagatattag tacaaaatac gtgacgtaga 120 aagtaataat ttcttgggta gtttgcagtt ttaaaattat gttttaaaat ggactatcat 180 atgcttaccg taacttgaaa gtatttcgat ttcttggctt tatatatctt gtggaaagga 240 cgaaacaccg gcgatgacga gatcacgcgg ttttagagct agaaatagca agttaaaata 300 aggctagtcc gttatcaact tgaaaaagtg gcaccgagtc ggtgcttttt tgttttagag 360 ctagaaatag caagttaaaa taaggctagt ccgtttttag cgcgtgcgcc aattctgcag 420 acaaatggct ctagaggtac ccgttacata acttacggta aatggcccgc ctggctgacc 480 gcccaacgac ccccgcccat tgacgtcaat agtaacgcca atagggactt tccattgacg 540 tcaatgggtg gagtatttac ggtaaactgc ccacttggca gtacatcaag tgtatcatat 600 gccaagtacg ccccctattg acgtcaatga cggtaaatgg cccgcctggc attgtgccca 660 gtacatgacc ttatgggact ttcctacttg gcagtacatc tacgtattag tcatcgctat 720 taccatggtc gaggtgagcc ccacgttctg cttcactctc cccatctccc ccccctcccc 780 acccccaatt ttgtatttat ttatttttta attattttgt gcagcgatgg gggcgggggg 840 gggggggggg cgcgcgccag gcggggcggg gcggggcgag gggcggggcg gggcgaggcg 900 gagaggtgcg gcggcagcca atcagagcgg cgcgctccga aagtttcctt ttatggcgag 960 gcggcggcgg cggcggccct ataaaaagcg aagcgcgcgg cgggcgggag tcgctgcgac 1020 gctgccttcg ccccgtgccc cgctccgccg ccgcctcgcg ccgcccgccc cggctctgac 1080 tgaccgcgtt actcccacag gtgagcgggc gggacggccc ttctcctccg ggctgtaatt 1140 agctgagcaa gaggtaaggg tttaagggat ggttggttgg tggggtatta atgtttaatt 1200 acctggagca cctgcctgaa atcacttttt ttcaggttgg accggtgcca ccatggacta 1260 taaggaccac gacggagact acaaggatca tgatattgat tacaaagacg atgacgataa 1320 gatggcccca aagaagaagc ggaaggtcgg tatccacgga gtcccagcag ccgacaagaa 1380 gtacagcatc ggcctggcca tcggcaccaa ctctgtgggc tgggccgtga tcaccgacga 1440 gtacaaggtg cccagcaaga aattcaaggt gctgggcaac accgaccggc acagcatcaa 1500 gaagaacctg atcggagccc tgctgttcga cagcggcgaa acagccgagg ccacccggct 1560 gaagagaacc gccagaagaa gatacaccag acggaagaac cggatctgct atctgcaaga 1620 gatcttcagc aacgagatgg ccaaggtgga cgacagcttc ttccacagac tggaagagtc 1680 cttcctggtg gaagaggata agaagcacga gcggcacccc atcttcggca acatcgtgga 1740 cgaggtggcc taccacgaga agtaccccac catctaccac ctgagaaaga aactggtgga 1800 cagcaccgac aaggccgacc tgcggctgat ctatctggcc ctggcccaca tgatcaagtt 1860 ccggggccac ttcctgatcg agggcgacct gaaccccgac aacagcgacg tggacaagct 1920 gttcatccag ctggtgcaga cctacaacca gctgttcgag gaaaacccca tcaacgccag 1980 cggcgtggac gccaaggcca tcctgtctgc cagactgagc aagagcagac ggctggaaaa 2040 tctgatcgcc cagctgcccg gcgagaagaa gaatggcctg ttcggcaacc tgattgccct 2100 gagcctgggc ctgaccccca acttcaagag caacttcgac ctggccgagg atgccaaact 2160 gcagctgagc aaggacacct acgacgacga cctggacaac ctgctggccc agatcggcga 2220 ccagtacgcc gacctgtttc tggccgccaa gaacctgtcc gacgccatcc tgctgagcga 2280 catcctgaga gtgaacaccg agatcaccaa ggcccccctg agcgcctcta tgatcaagag 2340 atacgacgag caccaccagg acctgaccct gctgaaagct ctcgtgcggc agcagctgcc 2400 tgagaagtac aaagagattt tcttcgacca gagcaagaac ggctacgccg gctacattga 2460 cggcggagcc agccaggaag agttctacaa gttcatcaag cccatcctgg aaaagatgga 2520 cggcaccgag gaactgctcg tgaagctgaa cagagaggac ctgctgcgga agcagcggac 2580 cttcgacaac ggcagcatcc cccaccagat ccacctggga gagctgcacg ccattctgcg 2640 gcggcaggaa gatttttacc cattcctgaa ggacaaccgg gaaaagatcg agaagatcct 2700 gaccttccgc atcccctact acgtgggccc tctggccagg ggaaacagca gattcgcctg 2760 gatgaccaga aagagcgagg aaaccatcac cccctggaac ttcgaggaag tggtggacaa 2820 gggcgcttcc gcccagagct tcatcgagcg gatgaccaac ttcgataaga acctgcccaa 2880 cgagaaggtg ctgcccaagc acagcctgct gtacgagtac ttcaccgtgt ataacgagct 2940 gaccaaagtg aaatacgtga ccgagggaat gagaaagccc gccttcctga gcggcgagca 3000 gaaaaaggcc atcgtggacc tgctgttcaa gaccaaccgg aaagtgaccg tgaagcagct 3060 gaaagaggac tacttcaaga aaatcgagtg cttcgactcc gtggaaatct ccggcgtgga 3120 agatcggttc aacgcctccc tgggcacata ccacgatctg ctgaaaatta tcaaggacaa 3180 ggacttcctg gacaatgagg aaaacgagga cattctggaa gatatcgtgc tgaccctgac 3240 actgtttgag gacagagaga tgatcgagga acggctgaaa acctatgccc acctgttcga 3300 cgacaaagtg atgaagcagc tgaagcggcg gagatacacc ggctggggca ggctgagccg 3360 gaagctgatc aacggcatcc gggacaagca gtccggcaag acaatcctgg atttcctgaa 3420 gtccgacggc ttcgccaaca gaaacttcat gcagctgatc cacgacgaca gcctgacctt 3480 taaagaggac atccagaaag cccaggtgtc cggccagggc gatagcctgc acgagcacat 3540 tgccaatctg gccggcagcc ccgccattaa gaagggcatc ctgcagacag tgaaggtggt 3600 ggacgagctc gtgaaagtga tgggccggca caagcccgag aacatcgtga tcgaaatggc 3660 cagagagaac cagaccaccc agaagggaca gaagaacagc cgcgagagaa tgaagcggat 3720 cgaagagggc atcaaagagc tgggcagcca gatcctgaaa gaacaccccg tggaaaacac 3780 ccagctgcag aacgagaagc tgtacctgta ctacctgcag aatgggcggg atatgtacgt 3840 ggaccaggaa ctggacatca accggctgtc cgactacgat gtggaccata tcgtgcctca 3900 gagctttctg aaggacgact ccatcgacaa caaggtgctg accagaagcg acaagaaccg 3960 gggcaagagc gacaacgtgc cctccgaaga ggtcgtgaag aagatgaaga actactggcg 4020 gcagctgctg aacgccaagc tgattaccca gagaaagttc gacaatctga ccaaggccga 4080 gagaggcggc ctgagcgaac tggataaggc cggcttcatc aagagacagc tggtggaaac 4140 ccggcagatc acaaagcacg tggcacagat cctggactcc cggatgaaca ctaagtacga 4200 cgagaatgac aagctgatcc gggaagtgaa agtgatcacc ctgaagtcca agctggtgtc 4260 cgatttccgg aaggatttcc agttttacaa agtgcgcgag atcaacaact accaccacgc 4320 ccacgacgcc tacctgaacg ccgtcgtggg aaccgccctg atcaaaaagt accctaagct 4380 ggaaagcgag ttcgtgtacg gcgactacaa ggtgtacgac gtgcggaaga tgatcgccaa 4440 gagcgagcag gaaatcggca aggctaccgc caagtacttc ttctacagca acatcatgaa 4500 ctttttcaag accgagatta ccctggccaa cggcgagatc cggaagcggc ctctgatcga 4560 gacaaacggc gaaaccgggg agatcgtgtg ggataagggc cgggattttg ccaccgtgcg 4620 gaaagtgctg agcatgcccc aagtgaatat cgtgaaaaag accgaggtgc agacaggcgg 4680 cttcagcaaa gagtctatcc tgcccaagag gaacagcgat aagctgatcg ccagaaagaa 4740 ggactgggac cctaagaagt acggcggctt cgacagcccc accgtggcct attctgtgct 4800 ggtggtggcc aaagtggaaa agggcaagtc caagaaactg aagagtgtga aagagctgct 4860 ggggatcacc atcatggaaa gaagcagctt cgagaagaat cccatcgact ttctggaagc 4920 caagggctac aaagaagtga aaaaggacct gatcatcaag ctgcctaagt actccctgtt 4980 cgagctggaa aacggccgga agagaatgct ggcctctgcc ggcgaactgc agaagggaaa 5040 cgaactggcc ctgccctcca aatatgtgaa cttcctgtac ctggccagcc actatgagaa 5100 gctgaagggc tcccccgagg ataatgagca gaaacagctg tttgtggaac agcacaagca 5160 ctacctggac gagatcatcg agcagatcag cgagttctcc aagagagtga tcctggccga 5220 cgctaatctg gacaaagtgc tgtccgccta caacaagcac cgggataagc ccatcagaga 5280 gcaggccgag aatatcatcc acctgtttac cctgaccaat ctgggagccc ctgccgcctt 5340 caagtacttt gacaccacca tcgaccggaa gaggtacacc agcaccaaag aggtgctgga 5400 cgccaccctg atccaccaga gcatcaccgg cctgtacgag acacggatcg acctgtctca 5460 gctgggaggc gacaaaaggc cggcggccac gaaaaaggcc ggccaggcaa aaaagaaaaa 5520 gtaagaattc ctagagctcg ctgatcagcc tcgactgtgc cttctagttg ccagccatct 5580 gttgtttgcc cctcccccgt gccttccttg accctggaag gtgccactcc cactgtcctt 5640 tcctaataaa atgaggaaat tgcatcgcat tgtctgagta ggtgtcattc tattctgggg 5700 ggtggggtgg ggcaggacag caagggggag gattgggaag agaatagcag gcatgctggg 5760 gagcggccgc aggaacccct agtgatggag ttggccactc cctctctgcg cgctcgctcg 5820 ctcactgagg ccgggcgacc aaaggtcgcc cgacgcccgg gctttgcccg ggcggcctca 5880 gtgagcgagc gagcgcgcag ctgcctgcag gggcgcctga tgcggtattt tctccttacg 5940 catctgtgcg gtatttcaca ccgcatacgt caaagcaacc atagtacgcg ccctgtagcg 6000 gcgcattaag cgcggcgggt gtggtggtta cgcgcagcgt gaccgctaca cttgccagcg 6060 ccctagcgcc cgctcctttc gctttcttcc cttcctttct cgccacgttc gccggctttc 6120 cccgtcaagc tctaaatcgg gggctccctt tagggttccg atttagtgct ttacggcacc 6180 tcgaccccaa aaaacttgat ttgggtgatg gttcacgtag tgggccatcg ccctgataga 6240 cggtttttcg ccctttgacg ttggagtcca cgttctttaa tagtggactc ttgttccaaa 6300 ctggaacaac actcaaccct atctcgggct attcttttga tttataaggg attttgccga 6360 tttcggccta ttggttaaaa aatgagctga tttaacaaaa atttaacgcg aattttaaca 6420 aaatattaac gtttacaatt ttatggtgca ctctcagtac aatctgctct gatgccgcat 6480 agttaagcca gccccgacac ccgccaacac ccgctgacgc gccctgacgg gcttgtctgc 6540 tcccggcatc cgcttacaga caagctgtga ccgtctccgg gagctgcatg tgtcagaggt 6600 tttcaccgtc atcaccgaaa cgcgcgagac gaaagggcct cgtgatacgc ctatttttat 6660 aggttaatgt catgataata atggtttctt agacgtcagg tggcactttt cggggaaatg 6720 tgcgcggaac ccctatttgt ttatttttct aaatacattc aaatatgtat ccgctcatga 6780 gacaataacc ctgataaatg cttcaataat attgaaaaag gaagagtatg agtattcaac 6840 atttccgtgt cgcccttatt cccttttttg cggcattttg ccttcctgtt tttgctcacc 6900 cagaaacgct ggtgaaagta aaagatgctg aagatcagtt gggtgcacga gtgggttaca 6960 tcgaactgga tctcaacagc ggtaagatcc ttgagagttt tcgccccgaa gaacgttttc 7020 caatgatgag cacttttaaa gttctgctat gtggcgcggt attatcccgt attgacgccg 7080 ggcaagagca actcggtcgc cgcatacact attctcagaa tgacttggtt gagtactcac 7140 cagtcacaga aaagcatctt acggatggca tgacagtaag agaattatgc agtgctgcca 7200 taaccatgag tgataacact gcggccaact tacttctgac aacgatcgga ggaccgaagg 7260 agctaaccgc ttttttgcac aacatggggg atcatgtaac tcgccttgat cgttgggaac 7320 cggagctgaa tgaagccata ccaaacgacg agcgtgacac cacgatgcct gtagcaatgg 7380 caacaacgtt gcgcaaacta ttaactggcg aactacttac tctagcttcc cggcaacaat 7440 taatagactg gatggaggcg gataaagttg caggaccact tctgcgctcg gcccttccgg 7500 ctggctggtt tattgctgat aaatctggag ccggtgagcg tggaagccgc ggtatcattg 7560 cagcactggg gccagatggt aagccctccc gtatcgtagt tatctacacg acggggagtc 7620 aggcaactat ggatgaacga aatagacaga tcgctgagat aggtgcctca ctgattaagc 7680 attggtaact gtcagaccaa gtttactcat atatacttta gattgattta aaacttcatt 7740 tttaatttaa aaggatctag gtgaagatcc tttttgataa tctcatgacc aaaatccctt 7800 aacgtgagtt ttcgttccac tgagcgtcag accccgtaga aaagatcaaa ggatcttctt 7860 gagatccttt ttttctgcgc gtaatctgct gcttgcaaac aaaaaaacca ccgctaccag 7920 cggtggtttg tttgccggat caagagctac caactctttt tccgaaggta actggcttca 7980 gcagagcgca gataccaaat actgtccttc tagtgtagcc gtagttaggc caccacttca 8040 agaactctgt agcaccgcct acatacctcg ctctgctaat cctgttacca gtggctgctg 8100 ccagtggcga taagtcgtgt cttaccgggt tggactcaag acgatagtta ccggataagg 8160 cgcagcggtc gggctgaacg gggggttcgt gcacacagcc cagcttggag cgaacgacct 8220 acaccgaact gagataccta cagcgtgagc tatgagaaag cgccacgctt cccgaaggga 8280 gaaaggcgga caggtatccg gtaagcggca gggtcggaac aggagagcgc acgagggagc 8340 ttccaggggg aaacgcctgg tatctttata gtcctgtcgg gtttcgccac ctctgacttg 8400 agcgtcgatt tttgtgatgc tcgtcagggg ggcggagcct atggaaaaac gccagcaacg 8460 cggccttttt acggttcctg gccttttgct ggccttttgc tcacatgt 8508 <210> 68 <211> 4032 <212> DNA <213> artificial sequence <220> <223> pZFN-AAVS1-L-ELD <400> 68 gactcttcgc gatgtacggg ccagatatac gcgttgacat tgattattga ctagttatta 60 atagtaatca attacggggt cattagttca tagcccatat atggagttcc gcgttacata 120 acttacggta aatggcccgc ctggctgacc gcccaacgac ccccgcccat tgacgtcaat 180 aatgacgtat gttcccatag taacgccaat agggactttc cattgacgtc aatgggtgga 240 ctatttacgg taaactgccc acttggcagt acatcaagtg tatcatatgc caagtacgcc 300 ccctattgac gtcaatgacg gtaaatggcc cgcctggcat tatgcccagt acatgacctt 360 atgggacttt cctacttggc agtacatcta cgtattagtc atcgctatta ccatggtgat 420 gcggttttgg cagtacatca atgggcgtgg atagcggttt gactcacggg gatttccaag 480 tctccacccc attgacgtca atgggagttt gttttggcac caaaatcaac gggactttcc 540 aaaatgtcgt aacaactccg ccccattgac gcaaatgggc ggtaggcgtg tacggtggga 600 ggtctatata agcagagctc tctggctaac tagagaaccc actgcttact ggcttatcga 660 aattaatacg actcactata gggagaccca agctggctag cgtttaaact taagctgatc 720 cactagtcca gtgtggtgga attcgccatg gactacaaag accatgacgg tgattataaa 780 gatcatgaca tcgattacaa ggatgacgat gacaagatgg cccccaagaa gaagaggaag 840 gtgggcattc acggggtacc cgccgctatg gccgagcggc ccttccagtg ccggatctgc 900 atgcggaact tcagctacaa ctggcatctg cagcggcaca tccggaccca caccggcgag 960 aagcccttcg cctgcgacat ctgcggccgg aagttcgcca gaagcgacca cctgaccacc 1020 cacaccaaga tccacacagg cagccagaaa ccttttcagt gcagaatctg tatgagaaac 1080 ttctcccaca actacgcccg ggactgccac atcagaacac acacagggga gaaacctttt 1140 gcctgcgata tctgtgggcg caaatttgcc cagaacagca cccggatcgg gcacacaaag 1200 attcacctga gaggatccca gctggtgaag agcgagctgg aggagaagaa gtccgagctg 1260 cggcacaagc tgaagtacgt gccccacgag tacatcgagc tgatcgagat cgccaggaac 1320 agcacccagg accgcatcct ggagatgaag gtgatggagt tcttcatgaa ggtgtacggc 1380 tacaggggaa agcacctggg cggaagcaga aagcctgacg gcgccatcta tacagtgggc 1440 agccccatcg attacggcgt gatcgtggac acaaaggcct acagcggcgg ctacaatctg 1500 cctatcggcc aggccgacga gatggagaga tacgtggagg agaaccagac ccgggataag 1560 cacctcaacc ccaacgagtg gtggaaggtg taccctagca gcgtgaccga gttcaagttc 1620 ctgttcgtga gcggccactt caagggcaac tacaaggccc agctgaccag gctgaaccac 1680 atcaccaact gcaatggcgc cgtgctgagc gtggaggagc tgctgatcgg cggcgagatg 1740 atcaaagccg gcaccctgac actggaggag gtgcggcgca agttcaacaa cggcgagatc 1800 aacttcagat cttgataact cgagtctaga gggcccgttt aaacccgctg atcagcctcg 1860 actgtgcctt ctagttgcca gccatctgtt gtttgcccct cccccgtgcc ttccttgacc 1920 ctggaaggtg ccactcccac tgtcctttcc taataaaatg aggaaattgc atcgcattgt 1980 ctgagtaggt gtcattctat tctggggggt ggggtggggc aggacagcaa gggggaggat 2040 tgggaagaca atagcaggca tgctggggat gcggtgggct ctatggcttc tactgggcgg 2100 ttttatggac agcaagcgaa ccggaattgc cagctggggc gccctctggt aaggttggga 2160 agccctgcaa agtaaactgg atggctttct cgccgccaag gatctgatgg cgcaggggat 2220 caagctctga tcaagagaca ggatgaggat cgtttcgcat gattgaacaa gatggattgc 2280 acgcaggttc tccggccgct tgggtggaga ggctattcgg ctatgactgg gcacaacaga 2340 caatcggctg ctctgatgcc gccgtgttcc ggctgtcagc gcaggggcgc ccggttcttt 2400 ttgtcaagac cgacctgtcc ggtgccctga atgaactgca agacgaggca gcgcggctat 2460 cgtggctggc cacgacgggc gttccttgcg cagctgtgct cgacgttgtc actgaagcgg 2520 gaagggactg gctgctattg ggcgaagtgc cggggcagga tctcctgtca tctcaccttg 2580 ctcctgccga gaaagtatcc atcatggctg atgcaatgcg gcggctgcat acgcttgatc 2640 cggctacctg cccattcgac caccaagcga aacatcgcat cgagcgagca cgtactcgga 2700 tggaagccgg tcttgtcgat caggatgatc tggacgaaga gcatcagggg ctcgcgccag 2760 ccgaactgtt cgccaggctc aaggcgagca tgcccgacgg cgaggatctc gtcgtgaccc 2820 atggcgatgc ctgcttgccg aatatcatgg tggaaaatgg ccgcttttct ggattcatcg 2880 actgtggccg gctgggtgtg gcggaccgct atcaggacat agcgttggct acccgtgata 2940 ttgctgaaga gcttggcggc gaatgggctg accgcttcct cgtgctttac ggtatcgccg 3000 ctcccgattc gcagcgcatc gccttctatc gccttcttga cgagttcttc tgaattatta 3060 acgcttacaa tttcctgatg cggtattttc tccttacgca tctgtgcggt atttcacacc 3120 gcatacaggt ggcacttttc ggggaaatgt gcgcggaacc cctatttgtt tatttttcta 3180 aatacattca aatatgtatc cgctcatgag acaataaccc tgataaatgc ttcaataata 3240 gcacgtgcta aaacttcatt tttaatttaa aaggatctag gtgaagatcc tttttgataa 3300 tctcatgacc aaaatccctt aacgtgagtt ttcgttccac tgagcgtcag accccgtaga 3360 aaagatcaaa ggatcttctt gagatccttt ttttctgcgc gtaatctgct gcttgcaaac 3420 aaaaaaacca ccgctaccag cggtggtttg tttgccggat caagagctac caactctttt 3480 tccgaaggta actggcttca gcagagcgca gataccaaat actgtccttc tagtgtagcc 3540 gtagttaggc caccacttca agaactctgt agcaccgcct acatacctcg ctctgctaat 3600 cctgttacca gtggctgctg ccagtggcga taagtcgtgt cttaccgggt tggactcaag 3660 acgatagtta ccggataagg cgcagcggtc gggctgaacg gggggttcgt gcacacagcc 3720 cagcttggag cgaacgacct acaccgaact gagataccta cagcgtgagc tatgagaaag 3780 cgccacgctt cccgaaggga gaaaggcgga caggtatccg gtaagcggca gggtcggaac 3840 aggagagcgc acgagggagc ttccaggggg aaacgcctgg tatctttata gtcctgtcgg 3900 gtttcgccac ctctgacttg agcgtcgatt tttgtgatgc tcgtcagggg ggcggagcct 3960 atggaaaaac gccagcaacg cggccttttt acggttcctg ggcttttgct ggccttttgc 4020 tcacatgttc tt 4032 <210> 69 <211> 4032 <212> DNA <213> artificial sequence <220> <223> pZFN-AAVS1-R_KKR <400> 69 gactcttcgc gatgtacggg ccagatatac gcgttgacat tgattattga ctagttatta 60 atagtaatca attacggggt cattagttca tagcccatat atggagttcc gcgttacata 120 acttacggta aatggcccgc ctggctgacc gcccaacgac ccccgcccat tgacgtcaat 180 aatgacgtat gttcccatag taacgccaat agggactttc cattgacgtc aatgggtgga 240 ctatttacgg taaactgccc acttggcagt acatcaagtg tatcatatgc caagtacgcc 300 ccctattgac gtcaatgacg gtaaatggcc cgcctggcat tatgcccagt acatgacctt 360 atgggacttt cctacttggc agtacatcta cgtattagtc atcgctatta ccatggtgat 420 gcggttttgg cagtacatca atgggcgtgg atagcggttt gactcacggg gatttccaag 480 tctccacccc attgacgtca atgggagttt gttttggcac caaaatcaac gggactttcc 540 aaaatgtcgt aacaactccg ccccattgac gcaaatgggc ggtaggcgtg tacggtggga 600 ggtctatata agcagagctc tctggctaac tagagaaccc actgcttact ggcttatcga 660 aattaatacg actcactata gggagaccca agctggctag cgtttaaact taagctgatc 720 cactagtcca gtgtggtgga attcgccatg gactacaaag accatgacgg tgattataaa 780 gatcatgaca tcgattacaa ggatgacgat gacaagatgg cccccaagaa gaagaggaag 840 gtgggcattc acggggtacc cgccgctatg gccgagcggc ccttccagtg ccggatctgc 900 atgcggaact ttagccagag cagcaacctg gcccggcaca tcagaaccca cacaggcgag 960 aagcccttcg cctgcgacat ctgcggccgg aagttcgccc ggaccgacta cctggtggac 1020 cacaccaaga tccacaccgg cagccagaaa ccttttcagt gcagaatctg tatgagaaac 1080 ttcagctaca acacccacct gaccagacac atccggacac acactgggga gaaacctttt 1140 gcctgcgata tctgtgggag aaagtttgcc cagggctaca atctggccgg gcacacaaag 1200 attcacctga gaggatccca gctggtgaag agcgagctgg aggagaagaa gtccgagctg 1260 cggcacaagc tgaagtacgt gccccacgag tacatcgagc tgatcgagat cgccaggaac 1320 agcacccagg accgcatcct ggagatgaag gtgatggagt tcttcatgaa ggtgtacggc 1380 tacaggggaa agcacctggg cggaagcaga aagcctgacg gcgccatcta tacagtgggc 1440 agccccatcg attacggcgt gatcgtggac acaaaggcct acagcggcgg ctacaatctg 1500 cctatcggcc aggccgacga gatgcagaga tacgtgaagg agaaccagac ccggaataag 1560 cacatcaacc ccaacgagtg gtggaaggtg taccctagca gcgtgaccga gttcaagttc 1620 ctgttcgtga gcggccactt caagggcaac tacaaggccc agctgaccag gctgaaccgc 1680 aaaaccaact gcaatggcgc cgtgctgagc gtggaggagc tgctgatcgg cggcgagatg 1740 atcaaagccg gcaccctgac actggaggag gtgcggcgca agttcaacaa cggcgagatc 1800 aacttcagat cttgataact cgagtctaga gggcccgttt aaacccgctg atcagcctcg 1860 actgtgcctt ctagttgcca gccatctgtt gtttgcccct cccccgtgcc ttccttgacc 1920 ctggaaggtg ccactcccac tgtcctttcc taataaaatg aggaaattgc atcgcattgt 1980 ctgagtaggt gtcattctat tctggggggt ggggtggggc aggacagcaa gggggaggat 2040 tgggaagaca atagcaggca tgctggggat gcggtgggct ctatggcttc tactgggcgg 2100 ttttatggac agcaagcgaa ccggaattgc cagctggggc gccctctggt aaggttggga 2160 agccctgcaa agtaaactgg atggctttct cgccgccaag gatctgatgg cgcaggggat 2220 caagctctga tcaagagaca ggatgaggat cgtttcgcat gattgaacaa gatggattgc 2280 acgcaggttc tccggccgct tgggtggaga ggctattcgg ctatgactgg gcacaacaga 2340 caatcggctg ctctgatgcc gccgtgttcc ggctgtcagc gcaggggcgc ccggttcttt 2400 ttgtcaagac cgacctgtcc ggtgccctga atgaactgca agacgaggca gcgcggctat 2460 cgtggctggc cacgacgggc gttccttgcg cagctgtgct cgacgttgtc actgaagcgg 2520 gaagggactg gctgctattg ggcgaagtgc cggggcagga tctcctgtca tctcaccttg 2580 ctcctgccga gaaagtatcc atcatggctg atgcaatgcg gcggctgcat acgcttgatc 2640 cggctacctg cccattcgac caccaagcga aacatcgcat cgagcgagca cgtactcgga 2700 tggaagccgg tcttgtcgat caggatgatc tggacgaaga gcatcagggg ctcgcgccag 2760 ccgaactgtt cgccaggctc aaggcgagca tgcccgacgg cgaggatctc gtcgtgaccc 2820 atggcgatgc ctgcttgccg aatatcatgg tggaaaatgg ccgcttttct ggattcatcg 2880 actgtggccg gctgggtgtg gcggaccgct atcaggacat agcgttggct acccgtgata 2940 ttgctgaaga gcttggcggc gaatgggctg accgcttcct cgtgctttac ggtatcgccg 3000 ctcccgattc gcagcgcatc gccttctatc gccttcttga cgagttcttc tgaattatta 3060 acgcttacaa tttcctgatg cggtattttc tccttacgca tctgtgcggt atttcacacc 3120 gcatacaggt ggcacttttc ggggaaatgt gcgcggaacc cctatttgtt tatttttcta 3180 aatacattca aatatgtatc cgctcatgag acaataaccc tgataaatgc ttcaataata 3240 gcacgtgcta aaacttcatt tttaatttaa aaggatctag gtgaagatcc tttttgataa 3300 tctcatgacc aaaatccctt aacgtgagtt ttcgttccac tgagcgtcag accccgtaga 3360 aaagatcaaa ggatcttctt gagatccttt ttttctgcgc gtaatctgct gcttgcaaac 3420 aaaaaaacca ccgctaccag cggtggtttg tttgccggat caagagctac caactctttt 3480 tccgaaggta actggcttca gcagagcgca gataccaaat actgtccttc tagtgtagcc 3540 gtagttaggc caccacttca agaactctgt agcaccgcct acatacctcg ctctgctaat 3600 cctgttacca gtggctgctg ccagtggcga taagtcgtgt cttaccgggt tggactcaag 3660 acgatagtta ccggataagg cgcagcggtc gggctgaacg gggggttcgt gcacacagcc 3720 cagcttggag cgaacgacct acaccgaact gagataccta cagcgtgagc tatgagaaag 3780 cgccacgctt cccgaaggga gaaaggcgga caggtatccg gtaagcggca gggtcggaac 3840 aggagagcgc acgagggagc ttccaggggg aaacgcctgg tatctttata gtcctgtcgg 3900 gtttcgccac ctctgacttg agcgtcgatt tttgtgatgc tcgtcagggg ggcggagcct 3960 atggaaaaac gccagcaacg cggccttttt acggttcctg ggcttttgct ggccttttgc 4020 tcacatgttc tt 4032 <210> 70 <211> 1068 <212> DNA <213> artificial sequence <220> <223> AAVS1-L_ZFN <400> 70 atggactaca aagaccatga cggtgattat aaagatcatg acatcgatta caaggatgac 60 gatgacaaga tggcccccaa gaagaagagg aaggtgggca ttcacggggt acccgccgct 120 atggccgagc ggcccttcca gtgccggatc tgcatgcgga acttcagcta caactggcat 180 ctgcagcggc acatccggac ccacaccggc gagaagccct tcgcctgcga catctgcggc 240 cggaagttcg ccagaagcga ccacctgacc acccacacca agatccacac aggcagccag 300 aaaccttttc agtgcagaat ctgtatgaga aacttctccc acaactacgc ccgggactgc 360 cacatcagaa cacacacagg ggagaaacct tttgcctgcg atatctgtgg gcgcaaattt 420 gcccagaaca gcacccggat cgggcacaca aagattcacc tgagaggatc ccagctggtg 480 aagagcgagc tggaggagaa gaagtccgag ctgcggcaca agctgaagta cgtgccccac 540 gagtacatcg agctgatcga gatcgccagg aacagcaccc aggaccgcat cctggagatg 600 aaggtgatgg agttcttcat gaaggtgtac ggctacaggg gaaagcacct gggcggaagc 660 agaaagcctg acggcgccat ctatacagtg ggcagcccca tcgattacgg cgtgatcgtg 720 gacacaaagg cctacagcgg cggctacaat ctgcctatcg gccaggccga cgagatggag 780 agatacgtgg aggagaacca gacccgggat aagcacctca accccaacga gtggtggaag 840 gtgtacccta gcagcgtgac cgagttcaag ttcctgttcg tgagcggcca cttcaagggc 900 aactacaagg cccagctgac caggctgaac cacatcacca actgcaatgg cgccgtgctg 960 agcgtggagg agctgctgat cggcggcgag atgatcaaag ccggcaccct gacactggag 1020 gaggtgcggc gcaagttcaa caacggcgag atcaacttca gatcttga 1068 <210> 71 <211> 1068 <212> DNA <213> artificial sequence <220> <223> AAVS1-R-ZFN <400> 71 atggactaca aagaccatga cggtgattat aaagatcatg acatcgatta caaggatgac 60 gatgacaaga tggcccccaa gaagaagagg aaggtgggca ttcacggggt acccgccgct 120 atggccgagc ggcccttcca gtgccggatc tgcatgcgga actttagcca gagcagcaac 180 ctggcccggc acatcagaac ccacacaggc gagaagccct tcgcctgcga catctgcggc 240 cggaagttcg cccggaccga ctacctggtg gaccacacca agatccacac cggcagccag 300 aaaccttttc agtgcagaat ctgtatgaga aacttcagct acaacaccca cctgaccaga 360 cacatccgga cacacactgg ggagaaacct tttgcctgcg atatctgtgg gagaaagttt 420 gcccagggct acaatctggc cgggcacaca aagattcacc tgagaggatc ccagctggtg 480 aagagcgagc tggaggagaa gaagtccgag ctgcggcaca agctgaagta cgtgccccac 540 gagtacatcg agctgatcga gatcgccagg aacagcaccc aggaccgcat cctggagatg 600 aaggtgatgg agttcttcat gaaggtgtac ggctacaggg gaaagcacct gggcggaagc 660 agaaagcctg acggcgccat ctatacagtg ggcagcccca tcgattacgg cgtgatcgtg 720 gacacaaagg cctacagcgg cggctacaat ctgcctatcg gccaggccga cgagatgcag 780 agatacgtga aggagaacca gacccggaat aagcacatca accccaacga gtggtggaag 840 gtgtacccta gcagcgtgac cgagttcaag ttcctgttcg tgagcggcca cttcaagggc 900 aactacaagg cccagctgac caggctgaac cgcaaaacca actgcaatgg cgccgtgctg 960 agcgtggagg agctgctgat cggcggcgag atgatcaaag ccggcaccct gacactggag 1020 gaggtgcggc gcaagttcaa caacggcgag atcaacttca gatcttga 1068 <210> 72 <211> 8351 <212> DNA <213> artificial sequence <220> <223> pUC_ROSA_n_CAG-rtTA <400> 72 tcgcgcgttt cggtgatgac ggtgaaaacc tctgacacat gcagctcccg gagacggtca 60 cagcttgtct gtaagcggat gccgggagca gacaagcccg tcagggcgcg tcagcgggtg 120 ttggcgggtg tcggggctgg cttaactatg cggcatcaga gcagattgta ctgagagtgc 180 accatatgcg gtgtgaaata ccgcacagat gcgtaaggag aaaataccgc atcaggcgcc 240 attcgccatt caggctgcgc aactgttggg aagggcgatc ggtgcgggcc tcttcgctat 300 tacgccagct ggcgaaaggg ggatgtgctg caaggcgatt aagttgggta acgccagggt 360 tttcccagtc acgacgttgt aaaacgacgg ccagtgaatt ggctcgaaac cggacggagc 420 cattgctctc gcagagggag gagcgcttcc ggctagcctc ttgtcgccga ttggccgttt 480 ctcctcccgc cgtgtgtgaa aacacaaatg gcgtattctg gttggagtaa agctcctgtc 540 agttacgccg tcgggagtac gcagccgctt agcgactctc gcgttgcccc ctgggtgggg 600 cgggtaggta ggtggggtgt agagatgctg ggtgtgcggg cgcggccggc ctcctgcggc 660 gggaggggag ggtcagtgaa atcggctctg gcgcgggcgt cctcccaccc tccccttcct 720 tcgggggagt cggtttaccc gccgcctgct tgtcttcgac acctgattgg ctgtcgaagc 780 tgtgggaccg ggcccttgct actggctcga gtctcacatg agcgaaacca ctgcgcgggg 840 cgcgggggtg gcggggaggc gggcgttggt acggtcctcc ccgaggccga gcgccgcagt 900 gtctggcccc gcgcccctgc gcaacgtggc aggaagcgcg cgctggaggc gggggcgggc 960 tgccggccga gacttctgga tggcggcggc cgcggctccg ccccgggttc ccaccgcctg 1020 aagggcgaga caagcccgac ctgctacagg cactcgtggg ggtgggggag gagcgggggt 1080 cggtccggct ggtttgtggg tgggaggcgc ttgttctcca aaaaccggcg cgagctgcaa 1140 tcctgaggga gctgcggtgg aggaggtgga gagaaggccg cacccttctg ggcaggggga 1200 ggggagtgcc gcaatacctt tatgggagtt ctctgctgcc tcccgtcttg taaggaccgc 1260 cctgggcctg gaagaagccc tccctccttt cctcctcgcg tgatcggtac ctagggcgca 1320 gtagtccagg gtttccttga tgatgtcata cttatcctgt cccttttttt tccacagctc 1380 gcggttgagg acaaactctt cgcggtcttt ccagtttcga acgggagatc tgccaccatg 1440 ggatcggcca ttgaacaaga tggattgcac gcaggttctc cggccgcttg ggtggagagg 1500 ctattcggct atgactgggc acaacagaca atcggctgct ctgatgccgc cgtgttccgg 1560 ctgtcagcgc aggggcgccc ggttcttttt gtcaagaccg acctgtccgg tgccctgaat 1620 gaactgcagg acgaggcagc gcggctatcg tggctggcca cgacgggcgt tccttgcgca 1680 gctgtgctcg acgttgtcac tgaagcggga agggactggc tgctattggg cgaagtgccg 1740 gggcaggatc tcctgtcatc tcaccttgct cctgccgaga aagtatccat catggctgat 1800 gcaatgcggc ggctgcatac gcttgatccg gctacctgcc cattcgacca ccaagcgaaa 1860 catcgcatcg agcgagcacg tactcggatg gaagccggtc ttgtcgatca ggatgatctg 1920 gacgaagagc atcaggggct cgcgccagcc gaactgttcg ccaggctcaa ggcgcgcatg 1980 cccgacggcg atgatctcgt cgtgacccat ggcgatgcct gcttgccgaa tatcatggtg 2040 gaaaatggcc gcttttctgg attcatcgac tgtggccggc tgggtgtggc ggaccgctat 2100 caggacatag cgttggctac ccgtgatatt gctgaagagc ttggcggcga atgggctgac 2160 cgcttcctcg tgctttacgg tatcgccgct cccgattcgc agcgcatcgc cttctatcgc 2220 cttcttgacg agttcttctg aggggatcaa ttctctagcg ctgatcagcc tcgactgtgc 2280 cttctagttg ccagccatct gttgtttgcc cctcccccgt gccttccttg accctggaag 2340 gtgccactcc cactgtcctt tcctaataaa atgaggaaat tgcatcgcat tgtctgagta 2400 ggtgtcattc tattctgggg ggtggggtgg ggcaggacag caagggggag gattgggaag 2460 acaatagcag gcatgctggg gatgcggtgg gctctatggc ttctgaggcg gaaagaacca 2520 gctggactag ttattaatag taatcaatta cggggtcatt agttcatagc ccatatatgg 2580 agttccgcgt tacataactt acggtaaatg gcccgcctgg ctgaccgccc aacgaccccc 2640 gcccattgac gtcaataatg acgtatgttc ccatagtaac gccaataggg actttccatt 2700 gacgtcaatg ggtggagtat ttacggtaaa ctgcccactt ggcagtacat caagtgtatc 2760 atatgccaag tacgccccct attgacgtca atgacggtaa atggcccgcc tggcattatg 2820 cccagtacat gaccttatgg gactttccta cttggcagta catctacgta ttagtcatcg 2880 ctattaccat ggtcgaggtg agccccacgt tctgcttcac tctccccatc tcccccccct 2940 ccccaccccc aattttgtat ttatttattt tttaattatt ttgtgcagcg atgggggcgg 3000 gggggggggg ggggcgcgcg ccaggcgggg cggggcgggg cgaggggcgg ggcggggcga 3060 ggcggagagg tgcggcggca gccaatcaga gcggcgcgct ccgaaagttt ccttttatgg 3120 cgaggcggcg gcggcggcgg ccctataaaa agcgaagcgc gcggcgggcg gggagtcgct 3180 gcgacgctgc cttcgccccg tgccccgctc cgccgccgcc tcgcgccgcc cgccccggct 3240 ctgactgacc gcgttactcc cacaggtgag cgggcgggac ggcccttctc ctccgggctg 3300 taattagcgc ttggtttaat gacggcttgt ttcttttctg tggctgcgtg aaagccttga 3360 ggggctccgg gagggccctt tgtgcggggg gagcggctcg gggggtgcgt gcgtgtgtgt 3420 gtgcgtgggg agcgccgcgt gcggctccgc gctgcccggc ggctgtgagc gctgcgggcg 3480 cggcgcgggg ctttgtgcgc tccgcagtgt gcgcgagggg agcgcggccg ggggcggtgc 3540 cccgcggtgc ggggggggct gcgaggggaa caaaggctgc gtgcggggtg tgtgcgtggg 3600 ggggtgagca gggggtgtgg gcgcgtcggt cgggctgcaa ccccccctgc acccccctcc 3660 ccgagttgct gagcacggcc cggcttcggg tgcggggctc cgtacggggc gtggcgcggg 3720 gctcgccgtg ccgggcgggg ggtggcggca ggtgggggtg ccgggcgggg cggggccgcc 3780 tcgggccggg gagggctcgg gggaggggcg cggcggcccc cggagcgccg gcggctgtcg 3840 aggcgcggcg agccgcagcc attgcctttt atggtaatcg tgcgagaggg cgcagggact 3900 tcctttgtcc caaatctgtg cggagccgaa atctgggagg cgccgccgca ccccctctag 3960 cgggcgcggg gcgaagcggt gcggcgccgg caggaaggaa atgggcgggg agggccttcg 4020 tgcgtcgccg cgccgccgtc cccttctccc tctccagcct cggggctgtc cgcgggggga 4080 cggctgcctt cgggggggac ggggcagggc ggggttcggc ttctggcgtg tgaccggcgg 4140 ctctagagcc tctgctaacc atgttcatgc cttcttcttt ttcctacagc tcctgggcaa 4200 cgtgctggtt attgtgctgt ctcatcattt tggcaaagaa ttaattcgga tccaccatgt 4260 ctagactgga caagagcaaa gtcataaact ctgctctgga attactcaat ggagtcggta 4320 tcgaaggcct gacgacaagg aaactcgctc aaaagctggg agttgagcag cctaccctgt 4380 actggcacgt gaagaacaag cgggccctgc tcgatgccct gccaatcgag atgctggaca 4440 ggcatcatac ccactcctgc cccctggaag gcgagtcatg gcaagacttt ctgcggaaca 4500 acgccaagtc ataccgctgt gctctcctct cacatcgcga cggggctaaa gtgcatctcg 4560 gcacccgccc aacagagaaa cagtacgaaa ccctggaaaa tcagctcgcg ttcctgtgtc 4620 agcaaggctt ctccctggag aacgcactgt acgctctgtc cgccgtgggc cactttacac 4680 tgggctgcgt attggaggaa caggagcatc aagtagcaaa agaggaaaga gagacaccta 4740 ccaccgattc tatgccccca cttctgaaac aagcaattga gctgttcgac cggcagggag 4800 ccgaacctgc cttccttttc ggcctggaac taatcatatg tggcctggag aaacagctaa 4860 agtgcgaaag cggcgggccg accgacgccc ttgacgattt tgacttagac atgctcccag 4920 ccgatgccct tgacgacttt gaccttgata tgctgcctgc tgacgctctt gacgattttg 4980 accttgacat gctccccggg taaacgcgta gctcgctgat cagcctcgac tgtgccttct 5040 agttgccagc catctgttgt ttgcccctcc cccgtgcctt ccttgaccct ggaaggtgcc 5100 actcccactg tcctttccta ataaaatgag gaaattgcat cgcattgtct gagtaggtgt 5160 cattctattc tggggggtgg ggtggggcag gacagcaagg gggaggattg ggaagagaat 5220 agcaggcatg ctgggggtcg acgcttctcg attatgggcg ggattctttt gcctaggctt 5280 aaggggctaa cttggtccct gggcgttgcc ctgcagggga gtgagcagct gtaagatttg 5340 aggggcgact ccgattagtt tatcttccca cggactagag ttggtgtcga ggttattgta 5400 ataagggtgg ggtagggaaa tggagcttag tcattcacct ggggctgatt ttatgcaacg 5460 agactgcgga ttatcactac ttatcatttt tggagcattt ttctagagac agacataaag 5520 catgatcacc tgagttttat accatttgag acccttgctg caccaccaaa gtgtagcatc 5580 aggttaaatc ttaatagaaa aattttagct tttgcttgag aaaccagtgc ttccctccct 5640 caccctctct ccccaggctc tctacccctt tgcatcccta ccaggcatct tagcaactct 5700 cactcatact tgatcccatt ttccatttgt tgtacttgct cctctagtat tcagacatag 5760 cactagcttt ctccctctct tgatcttggg tagcctggtg tctcgcgaaa ccagacagat 5820 tggttccacc acaaattaag gcttgagctg gggcttgact cttacccagc agtgctttta 5880 ttcctcccta gttcacgttc ttaaatgttt atcttgattt tcattttatc ctttttcctt 5940 agctgggatt ctgtccctga ccgtcttcac agtccaggtg atcttgacta ctgctttaca 6000 gagaattgga tctgaggtta ggcaacatct ccctttttct tcctctaaat acctctcatt 6060 tctgttctta ccagttagta actgatctca gatgcctgtg tgatagcttc caagcttggc 6120 gtaatcatgg tcatagctgt ttcctgtgtg aaattgttat ccgctcacaa ttccacacaa 6180 catacgagcc ggaagcataa agtgtaaagc ctggggtgcc taatgagtga gctaactcac 6240 attaattgcg ttgcgctcac tgcccgcttt ccagtcggga aacctgtcgt gccagctgca 6300 ttaatgaatc ggccaacgcg cggggagagg cggtttgcgt attgggcgct cttccgcttc 6360 ctcgctcact gactcgctgc gctcggtcgt tcggctgcgg cgagcggtat cagctcactc 6420 aaaggcggta atacggttat ccacagaatc aggggataac gcaggaaaga acatgtgagc 6480 aaaaggccag caaaaggcca ggaaccgtaa aaaggccgcg ttgctggcgt ttttccatag 6540 gctccgcccc cctgacgagc atcacaaaaa tcgacgctca agtcagaggt ggcgaaaccc 6600 gacaggacta taaagatacc aggcgtttcc ccctggaagc tccctcgtgc gctctcctgt 6660 tccgaccctg ccgcttaccg gatacctgtc cgcctttctc ccttcgggaa gcgtggcgct 6720 ttctcatagc tcacgctgta ggtatctcag ttcggtgtag gtcgttcgct ccaagctggg 6780 ctgtgtgcac gaaccccccg ttcagcccga ccgctgcgcc ttatccggta actatcgtct 6840 tgagtccaac ccggtaagac acgacttatc gccactggca gcagccactg gtaacaggat 6900 tagcagagcg aggtatgtag gcggtgctac agagttcttg aagtggtggc ctaactacgg 6960 ctacactaga agaacagtat ttggtatctg cgctctgctg aagccagtta ccttcggaaa 7020 aagagttggt agctcttgat ccggcaaaca aaccaccgct ggtagcggtg gtttttttgt 7080 ttgcaagcag cagattacgc gcagaaaaaa aggatctcaa gaagatcctt tgatcttttc 7140 tacggggtct gacgctcagt ggaacgaaaa ctcacgttaa gggattttgg tcatgagatt 7200 atcaaaaagg atcttcacct agatcctttt aaattaaaaa tgaagtttta aatcaatcta 7260 aagtatatat gagtaaactt ggtctgacag ttaccaatgc ttaatcagtg aggcacctat 7320 ctcagcgatc tgtctatttc gttcatccat agttgcctga ctccccgtcg tgtagataac 7380 tacgatacgg gagggcttac catctggccc cagtgctgca atgataccgc gagacccacg 7440 ctcaccggct ccagatttat cagcaataaa ccagccagcc ggaagggccg agcgcagaag 7500 tggtcctgca actttatccg cctccatcca gtctattaat tgttgccggg aagctagagt 7560 aagtagttcg ccagttaata gtttgcgcaa cgttgttgcc attgctacag gcatcgtggt 7620 gtcacgctcg tcgtttggta tggcttcatt cagctccggt tcccaacgat caaggcgagt 7680 tacatgatcc cccatgttgt gcaaaaaagc ggttagctcc ttcggtcctc cgatcgttgt 7740 cagaagtaag ttggccgcag tgttatcact catggttatg gcagcactgc ataattctct 7800 tactgtcatg ccatccgtaa gatgcttttc tgtgactggt gagtactcaa ccaagtcatt 7860 ctgagaatag tgtatgcggc gaccgagttg ctcttgcccg gcgtcaatac gggataatac 7920 cgcgccacat agcagaactt taaaagtgct catcattgga aaacgttctt cggggcgaaa 7980 actctcaagg atcttaccgc tgttgagatc cagttcgatg taacccactc gtgcacccaa 8040 ctgatcttca gcatctttta ctttcaccag cgtttctggg tgagcaaaaa caggaaggca 8100 aaatgccgca aaaaagggaa taagggcgac acggaaatgt tgaatactca tactcttcct 8160 ttttcaatat tattgaagca tttatcaggg ttattgtctc atgagcggat acatatttga 8220 atgtatttag aaaaataaac aaataggggt tccgcgcaca tttccccgaa aagtgccacc 8280 tgacgtctaa gaaaccatta ttatcatgac attaacctat aaaaataggc gtatcacgag 8340 gccctttcgt c 8351 <210> 73 <211> 2477 <212> DNA <213> artificial sequence <220> <223> vector CAG-rtTA <400> 73 ctagttatta atagtaatca attacggggt cattagttca tagcccatat atggagttcc 60 gcgttacata acttacggta aatggcccgc ctggctgacc gcccaacgac ccccgcccat 120 tgacgtcaat aatgacgtat gttcccatag taacgccaat agggactttc cattgacgtc 180 aatgggtgga gtatttacgg taaactgccc acttggcagt acatcaagtg tatcatatgc 240 caagtacgcc ccctattgac gtcaatgacg gtaaatggcc cgcctggcat tatgcccagt 300 acatgacctt atgggacttt cctacttggc agtacatcta cgtattagtc atcgctatta 360 ccatggtcga ggtgagcccc acgttctgct tcactctccc catctccccc ccctccccac 420 ccccaatttt gtatttattt attttttaat tattttgtgc agcgatgggg gcgggggggg 480 ggggggggcg cgcgccaggc ggggcggggc ggggcgaggg gcggggcggg gcgaggcgga 540 gaggtgcggc ggcagccaat cagagcggcg cgctccgaaa gtttcctttt atggcgaggc 600 ggcggcggcg gcggccctat aaaaagcgaa gcgcgcggcg ggcggggagt cgctgcgacg 660 ctgccttcgc cccgtgcccc gctccgccgc cgcctcgcgc cgcccgcccc ggctctgact 720 gaccgcgtta ctcccacagg tgagcgggcg ggacggccct tctcctccgg gctgtaatta 780 gcgcttggtt taatgacggc ttgtttcttt tctgtggctg cgtgaaagcc ttgaggggct 840 ccgggagggc cctttgtgcg gggggagcgg ctcggggggt gcgtgcgtgt gtgtgtgcgt 900 ggggagcgcc gcgtgcggct ccgcgctgcc cggcggctgt gagcgctgcg ggcgcggcgc 960 ggggctttgt gcgctccgca gtgtgcgcga ggggagcgcg gccgggggcg gtgccccgcg 1020 gtgcgggggg ggctgcgagg ggaacaaagg ctgcgtgcgg ggtgtgtgcg tgggggggtg 1080 agcagggggt gtgggcgcgt cggtcgggct gcaacccccc ctgcaccccc ctccccgagt 1140 tgctgagcac ggcccggctt cgggtgcggg gctccgtacg gggcgtggcg cggggctcgc 1200 cgtgccgggc ggggggtggc ggcaggtggg ggtgccgggc ggggcggggc cgcctcgggc 1260 cggggagggc tcgggggagg ggcgcggcgg cccccggagc gccggcggct gtcgaggcgc 1320 ggcgagccgc agccattgcc ttttatggta atcgtgcgag agggcgcagg gacttccttt 1380 gtcccaaatc tgtgcggagc cgaaatctgg gaggcgccgc cgcaccccct ctagcgggcg 1440 cggggcgaag cggtgcggcg ccggcaggaa ggaaatgggc ggggagggcc ttcgtgcgtc 1500 gccgcgccgc cgtccccttc tccctctcca gcctcggggc tgtccgcggg gggacggctg 1560 ccttcggggg ggacggggca gggcggggtt cggcttctgg cgtgtgaccg gcggctctag 1620 agcctctgct aaccatgttc atgccttctt ctttttccta cagctcctgg gcaacgtgct 1680 ggttattgtg ctgtctcatc attttggcaa agaattaatt cggatccacc atgtctagac 1740 tggacaagag caaagtcata aactctgctc tggaattact caatggagtc ggtatcgaag 1800 gcctgacgac aaggaaactc gctcaaaagc tgggagttga gcagcctacc ctgtactggc 1860 acgtgaagaa caagcgggcc ctgctcgatg ccctgccaat cgagatgctg gacaggcatc 1920 atacccactc ctgccccctg gaaggcgagt catggcaaga ctttctgcgg aacaacgcca 1980 agtcataccg ctgtgctctc ctctcacatc gcgacggggc taaagtgcat ctcggcaccc 2040 gcccaacaga gaaacagtac gaaaccctgg aaaatcagct cgcgttcctg tgtcagcaag 2100 gcttctccct ggagaacgca ctgtacgctc tgtccgccgt gggccacttt acactgggct 2160 gcgtattgga ggaacaggag catcaagtag caaaagagga aagagagaca cctaccaccg 2220 attctatgcc cccacttctg aaacaagcaa ttgagctgtt cgaccggcag ggagccgaac 2280 ctgccttcct tttcggcctg gaactaatca tatgtggcct ggagaaacag ctaaagtgcg 2340 aaagcggcgg gccgaccgac gcccttgacg attttgactt agacatgctc ccagccgatg 2400 cccttgacga ctttgacctt gatatgctgc ctgctgacgc tcttgacgat tttgaccttg 2460 acatgctccc cgggtaa 2477 <210> 74 <211> 2154 <212> DNA <213> artificial sequence <220> <223> PU.1-IRF8 <400> 74 atgttacagg cgtgcaaaat ggaagggttt cccctcgtcc cccctccatc agaagacctg 60 gtgccctatg acacggatct ataccaacgc caaacgcacg agtattaccc ctatctcagc 120 agtgatgggg agagccatag cgaccattac tgggacttcc acccccacca cgtgcacagc 180 gagttcgaga gcttcgccga gaacaacttc acggagctcc agagcgtgca gcccccgcag 240 ctgcagcagc tctaccgcca catggagctg gagcagatgc acgtcctcga tacccccatg 300 gtgccacccc atcccagtct tggccaccag gtctcctacc tgccccggat gtgcctccag 360 tacccatccc tgtccccagc ccagcccagc tcagatgagg aggagggcga gcggcagagc 420 cccccactgg aggtgtctga cggcgaggcg gatggcctgg agcccgggcc tgggctcctg 480 cctggggaga caggcagcaa gaagaagatc cgcctgtacc agttcctgtt ggacctgctc 540 cgcagcggcg acatgaagga cagcatctgg tgggtggaca aggacaaggg caccttccag 600 ttctcgtcca agcacaagga ggcgctggcg caccgctggg gcatccagaa gggcaaccgc 660 aagaagatga cctaccagaa gatggcgcgc gcgctgcgca actacggcaa gacgggcgag 720 gtcaagaagg tgaagaagaa gctcacctac cagttcagcg gcgaagtgct gggccgcggg 780 ggcctggccg agcggcgcca cccgccccac ggatcgggag agggcagggg aagtcttcta 840 acatgcgggg acgtggagga aaatcccggc cccatgtgtg accggaatgg tggtcggcgg 900 cttcgacagt ggctgatcga gcagattgac agtagcatgt atccaggact gatttgggag 960 aatgaggaga agagcatgtt ccggatccct tggaaacacg ctggcaagca agattataat 1020 caggaagtgg atgcctccat ttttaaggcc tgggcagttt ttaaagggaa gtttaaagaa 1080 ggggacaaag ctgaaccagc cacttggaag acgaggttac gctgtgcttt gaataagagc 1140 ccagattttg aggaagtgac ggaccggtcc caactggaca tttccgagcc atacaaagtt 1200 taccgaattg ttcctgagga agagcaaaaa tgcaaactag gcgtggcaac tgctggctgc 1260 gtgaatgaag ttacagagat ggagtgcggt cgctctgaaa tcgacgagct gatcaaggag 1320 ccttctgtgg acgattacat ggggatgatc aaaaggagcc cttccccgcc ggaggcctgt 1380 cggagtcagc tccttccaga ctggtgggcg cagcagccca gcacaggcgt gccgctggtg 1440 acggggtaca ccacctacga cgcgcaccat tcagcattct cccagatggt gatcagcttc 1500 tactatgggg gcaagctggt gggccaggcc accaccacct gccccgaggg ctgccgcctg 1560 tccctgagcc agcctgggct gcccggcacc aagctgtatg ggcccgaggg cctggagctg 1620 gtgcgcttcc cgccggccga cgccatcccc agcgagcgac agaggcaggt gacgcggaag 1680 ctgttcgggc acctggagcg cggggtgctg ctgcacagca gccggcaggg cgtgttcgtc 1740 aagcggctgt gccagggccg cgtgttctgc agcggcaacg ccgtggtgtg caaaggcagg 1800 cccaacaagc tggagcgtga tgaggtggtc caggtcttcg acaccagcca gttcttccga 1860 gagctgcagc agttctataa cagccagggc cggcttcctg acggcagggt ggtgctgtgc 1920 tttggggaag agtttccgga tatggccccc ttgcgctcca aactcattct cgtgcagatt 1980 gagcagctgt atgtccggca actggcagaa gaggctggga agagctgtgg agccggctct 2040 gtgatgcagg cccccgagga gccgccgcca gaccaggtct tccggatgtt tccagatatt 2100 tgtgcctcac accagagatc atttttcaga gaaaaccaac agatcaccgt ctaa 2154 <210> 75 <211> 2321 <212> DNA <213> artificial sequence <220> <223> PU.1-RUNX1 <400> 75 atgttacagg cgtgcaaaat ggaagggttt cccctcgtcc cccctccatc agaagacctg 60 gtgccctatg acacggatct ataccaacgc caaacgcacg agtattaccc ctatctcagc 120 agtgatgggg agagccatag cgaccattac tgggacttcc acccccacca cgtgcacagc 180 gagttcgaga gcttcgccga gaacaacttc acggagctcc agagcgtgca gcccccgcag 240 ctgcagcagc tctaccgcca catggagctg gagcagatgc acgtcctcga tacccccatg 300 gtgccacccc atcccagtct tggccaccag gtctcctacc tgccccggat gtgcctccag 360 tacccatccc tgtccccagc ccagcccagc tcagatgagg aggagggcga gcggcagagc 420 cccccactgg aggtgtctga cggcgaggcg gatggcctgg agcccgggcc tgggctcctg 480 cctggggaga caggcagcaa gaagaagatc cgcctgtacc agttcctgtt ggacctgctc 540 cgcagcggcg acatgaagga cagcatctgg tgggtggaca aggacaaggg caccttccag 600 ttctcgtcca agcacaagga ggcgctggcg caccgctggg gcatccagaa gggcaaccgc 660 aagaagatga cctaccagaa gatggcgcgc gcgctgcgca actacggcaa gacgggcgag 720 gtcaagaagg tgaagaagaa gctcacctac cagttcagcg gcgaagtgct gggccgcggg 780 ggcctggccg agcggcgcca cccgccccac ggatcgggag agggcagggg aagtcttcta 840 acatgcgggg acgtggagga aaatcccggc cccatggctt cagacagcat atttgagtca 900 tttccttcgt acccacagtg cttcatgaga gaatgcatac ttggaatgaa tccttctaga 960 gacgtccacg atgccagcac gagccgccgc ttcacgccgc cttccaccgc gctgagccca 1020 ggcaagatga gcgaggcgtt gccgctgggc gccccggacg ccggcgctgc cctggccggc 1080 aagctgagga gcggcgaccg cagcatggtg gaggtgctgg ccgaccaccc gggcgagctg 1140 gtgcgcaccg acagccccaa cttcctctgc tccgtgctgc ctacgcactg gcgctgcaac 1200 aagaccctgc ccatcgcttt caaggtggtg gccctagggg atgttccaga tggcactctg 1260 gtcactgtga tggctggcaa tgatgaaaac tactcggctg agctgagaaa tgctaccgca 1320 gccatgaaga accaggttgc aagatttaat gacctcaggt ttgtcggtcg aagtggaaga 1380 gggaaaagct tcactctgac catcactgtc ttcacaaacc caccgcaagt cgccacctac 1440 cacagagcca tcaaaatcac agtggatggg ccccgagaac ctcgaagaca tcggcagaaa 1500 ctagatgatc agaccaagcc cgggagcttg tccttttccg agcggctcag tgaactggag 1560 cagctgcggc gcacagccat gagggtcagc ccacaccacc cagcccccac gcccaaccct 1620 cgtgcctccc tgaaccactc cactgccttt aaccctcagc ctcagagtca gatgcaggat 1680 acaaggcaga tccaaccatc cccaccgtgg tcctacgatc agtcctacca atacctggga 1740 tccattgcct ctccttctgt gcacccagca acgcccattt cacctggacg tgccagcggc 1800 atgacaaccc tctctgcaga actttccagt cgactctcaa cggcacccga cctgacagcg 1860 ttcagcgacc cgcgccagtt ccccgcgctg ccctccatct ccgacccccg catgcactat 1920 ccaggcgcct tcacctactc cccgacgccg gtcacctcgg gcatcggcat cggcatgtcg 1980 gccatgggct cggccacgcg ctaccacacc tacctgccgc cgccctaccc cggctcgtcg 2040 caagcgcagg gaggcccgtt ccaagccagc tcgccctcct accacctgta ctacggcgcc 2100 tcggccggct cctaccagtt ctccatggtg ggcggcgagc gctcgccgcc gcgcatcctg 2160 ccgccctgca ccaacgcctc caccggctcc gcgctgctca accccagcct cccgaaccag 2220 agcgacgtgg tggaggccga gggcagccac agcaactccc cgaccaacat ggcgccctcc 2280 gcgcgcctgg aggaggccgt gtggaggccc tacaccggtt g 2321 <210> 76 <211> 1911 <212> DNA <213> artificial sequence <220> <223> PU.1-CEBPB <400> 76 atgttacagg cgtgcaaaat ggaagggttt cccctcgtcc cccctccatc agaagacctg 60 gtgccctatg acacggatct ataccaacgc caaacgcacg agtattaccc ctatctcagc 120 agtgatgggg agagccatag cgaccattac tgggacttcc acccccacca cgtgcacagc 180 gagttcgaga gcttcgccga gaacaacttc acggagctcc agagcgtgca gcccccgcag 240 ctgcagcagc tctaccgcca catggagctg gagcagatgc acgtcctcga tacccccatg 300 gtgccacccc atcccagtct tggccaccag gtctcctacc tgccccggat gtgcctccag 360 tacccatccc tgtccccagc ccagcccagc tcagatgagg aggagggcga gcggcagagc 420 cccccactgg aggtgtctga cggcgaggcg gatggcctgg agcccgggcc tgggctcctg 480 cctggggaga caggcagcaa gaagaagatc cgcctgtacc agttcctgtt ggacctgctc 540 cgcagcggcg acatgaagga cagcatctgg tgggtggaca aggacaaggg caccttccag 600 ttctcgtcca agcacaagga ggcgctggcg caccgctggg gcatccagaa gggcaaccgc 660 aagaagatga cctaccagaa gatggcgcgc gcgctgcgca actacggcaa gacgggcgag 720 gtcaagaagg tgaagaagaa gctcacctac cagttcagcg gcgaagtgct gggccgcggg 780 ggcctggccg agcggcgcca cccgccccac ggatcgggag agggcagggg aagtcttcta 840 acatgcgggg acgtggagga aaatcccggc cccatgcaac gcctggtggc ctgggaccca 900 gcatgtctcc ccctgccgcc gccgccgcct gcctttaaat ccatggaagt ggccaacttc 960 tactacgagg cggactgctt ggctgctgcg tacggcggca aggcggcccc cgcggcgccc 1020 cccgcggcca gacccgggcc gcgccccccc gccggcgagc tgggcagcat cggcgaccac 1080 gagcgcgcca tcgacttcag cccgtacctg gagccgctgg gcgcgccgca ggccccggcg 1140 cccgccacgg ccacggacac cttcgaggcg gctccgcccg cgcccgcccc cgcgcccgcc 1200 tcctccgggc agcaccacga cttcctctcc gacctcttct ccgacgacta cgggggcaag 1260 aactgcaaga agccggccga gtacggctac gtgagcctgg ggcgcctggg ggccgccaag 1320 ggcgcgctgc accccggctg cttcgcgccc ctgcacccac cgcccccgcc gccgccgccg 1380 cccgccgagc tcaaggcgga gccgggcttc gagcccgcgg actgcaagcg gaaggaggag 1440 gccggggcgc cgggcggcgg cgcaggcatg gcggcgggct tcccgtacgc gctgcgcgct 1500 tacctcggct accaggcggt gccgagcggc agcagcggga gcctctccac gtcctcctcg 1560 tccagcccgc ccggcacgcc gagccccgct gacgccaagg cgcccccgac cgcctgctac 1620 gcgggggccg cgccggcgcc ctcgcaggtc aagagcaagg ccaagaagac cgtggacaag 1680 cacagcgacg agtacaagat ccggcgcgag cgcaacaaca tcgccgtgcg caagagccgc 1740 gacaaggcca agatgcgcaa cctggagacg cagcacaagg tcctggagct cacggccgag 1800 aacgagcggc tgcagaagaa ggtggagcag ctgtcgcgcg agctcagcac cctgcggaac 1860 ttgttcaagc agctgcccga gcccctgctc gcctcctccg gccactgcta g 1911 <210> 77 <211> 4848 <212> DNA <213> artificial sequence <220> <223> PU.1-SALL1 <400> 77 atgttacagg cgtgcaaaat ggaagggttt cccctcgtcc cccctccatc agaagacctg 60 gtgccctatg acacggatct ataccaacgc caaacgcacg agtattaccc ctatctcagc 120 agtgatgggg agagccatag cgaccattac tgggacttcc acccccacca cgtgcacagc 180 gagttcgaga gcttcgccga gaacaacttc acggagctcc agagcgtgca gcccccgcag 240 ctgcagcagc tctaccgcca catggagctg gagcagatgc acgtcctcga tacccccatg 300 gtgccacccc atcccagtct tggccaccag gtctcctacc tgccccggat gtgcctccag 360 tacccatccc tgtccccagc ccagcccagc tcagatgagg aggagggcga gcggcagagc 420 cccccactgg aggtgtctga cggcgaggcg gatggcctgg agcccgggcc tgggctcctg 480 cctggggaga caggcagcaa gaagaagatc cgcctgtacc agttcctgtt ggacctgctc 540 cgcagcggcg acatgaagga cagcatctgg tgggtggaca aggacaaggg caccttccag 600 ttctcgtcca agcacaagga ggcgctggcg caccgctggg gcatccagaa gggcaaccgc 660 aagaagatga cctaccagaa gatggcgcgc gcgctgcgca actacggcaa gacgggcgag 720 gtcaagaagg tgaagaagaa gctcacctac cagttcagcg gcgaagtgct gggccgcggg 780 ggcctggccg agcggcgcca cccgccccac ggatcgggag agggcagggg aagtcttcta 840 acatgcgggg acgtggagga aaatcccggc cccatgtcgc ggaggaagca agcgaagcct 900 caacatttcc aatccgaccc cgaagtggcc tcgctccccc ggcgagatgg agacacagaa 960 aagggtcaac cgagtcgccc tactaagagc aaggatgccc acgtctgtgg ccggtgctgt 1020 gccgagttct ttgaattatc agatcttctg ctccacaaga agaactgtac taaaaatcaa 1080 ttagttttaa tcgtaaatga aaatccagcc tccccacccg aaaccttctc ccccagcccc 1140 cctcctgata atcctgatga acaaatgaat gacacagtta acaaaacaga tcaagtggac 1200 tgcagcgacc tttcagaaca caacggactt gacagggaag agtccatgga ggtggaggcc 1260 ccggttgcta acaaaagcgg cagcggcact tccagcggca gccacagcag taccgcccca 1320 agcagcagca gcagcagcag cagcagcagc ggcggcggcg gcagctcctc cacaggtacc 1380 tcagcgatca caacctctct acctcaactc ggggacctga caacactggg caacttctcc 1440 gtaatcaaca gcaacgtcat catcgagaac ctccagagca ccaaggtggc ggtggcccag 1500 ttctcccagg aagcgaggtg cggcggggcc tctgggggca agctggccgt cccagccctc 1560 atggaacaac tcctagctct gcagcagcag cagatccacc agctgcaatt gatcgaacag 1620 attcgtcacc aaatattgct gttggcttct cagaatgcag acttgccaac atcttctagt 1680 ccttctcaag gtactttacg aacatctgcc aaccccttgt ccacgctaag ttcccattta 1740 tctcagcagc tggcagcagc agctggattg gcacagagcc tcgccagcca atctgccagc 1800 attagtggtg tgaaacagct acccccaatc cagctacctc agagcagttc tggcaacacc 1860 atcattccat ccaacagcgg ctcttctccc aatatgaaca tattggcagc ggcagttacc 1920 accccgtcct ctgaaaaagt ggcttcaagt gctggggcct cccatgtcag caacccagcg 1980 gtctcatcat cgtcctcacc agcttttgca ataagcagtt tattaagtcc tgcgtctaat 2040 ccacttctac ctcagcaagc ctccgctaac tcggttttcc ccagcccttt gcccaacatc 2100 ggaacaactg cagaggattt aaactccttg tctgccttgg cccagcaaag aaaaagcaag 2160 ccaccaaatg tcactgcctt tgaagcgaaa agtacttccg atgaggcatt cttcaaacac 2220 aagtgcaggt tctgcgcgaa ggtctttggg agtgacagtg ccttgcagat ccacttgcgt 2280 tcccataccg gagagaggcc attcaagtgc aacatctgcg ggaacaggtt ctccaccaag 2340 gggaatctga aagtccactt tcagcgccac aaagagaaat accctcatat ccagatgaac 2400 ccctatcctg tgcctgagca tttggacaat atccccacga gtactggcat cccatatggc 2460 atgtccatcc ctccagagaa gccagtcacc agctggctag acaccaaacc agtcctgcct 2520 actctgacca cttcagtcgg cctgccgttg cccccaaccc tcccaagcct catacccttc 2580 atcaagacgg aagagccagc ccccatcccc atcagccatt ctgccaccag ccccccaggc 2640 tcagtcaaaa gtgactccgg gggccctgag tcagccacaa gaaacctagg tgggctccca 2700 gaggaagccg aagggtccac tctgccaccc tctggtggca aaagcgaaga gagtggcatg 2760 gtcaccaact cagtcccgac ggcgagcagt agcgtcctga gctccccagc ggcagactgc 2820 ggccccgcgg gcagtgccac caccttcacc aaccctttgt tgccgctcat gtccgagcag 2880 ttcaaggcca agtttccttt tgggggactc ctggactcag ctcaggcatc agagacgtcc 2940 aagcttcagc aactggtaga aaacattgac aagaaggcca ctgaccccaa tgagtgcatc 3000 atctgccacc gggttctcag ctgccagagc gccttgaaaa tgcactacag gacacacact 3060 ggggagaggc cctttaagtg taagatctgt ggccgggctt tcaccacgaa agggaatctt 3120 aaaacccact acagtgtcca tcgtgctatg cccccgctca gagtccagca ttcctgcccc 3180 atctgccaga agaagttcac gaacgctgtg gtcctgcagc agcacatccg aatgcatatg 3240 ggaggccaga tccccaacac cccagtcccc gacagctact ctgagtccat ggagtctgac 3300 acaggttcct ttgatgagaa aaattttgat gacctagaca acttctctga tgaaaacatg 3360 gaagactgtc ctgagggcag catccctgat acacctaagt ctgcagacgc ctcccaagac 3420 agcttatcct cttcgccttt gcccctcgag atgtcgagca tcgctgcttt ggaaaatcag 3480 atgaagatga tcaatgctgg cctggcagag cagctacagg ccagcctgaa gtcagtggag 3540 aatgggtcca tcgaggggga tgtcctgacc aatgattcat cctcagtggg tggtgacatg 3600 gaaagccaaa gtgctggcag cccagccatc tcagagtcta cctcttccat gcaggctctg 3660 tccccgtcca acagcacgca ggagttccac aagtcaccca gcattgagga gaaaccacag 3720 agagcggtcc caagcgagtt tgccaatggt ttgtctccca ccccagtgaa tggtggggct 3780 ttggatttga catctagtca cgcagagaaa atcatcaaag aagattcttt ggggatcctc 3840 ttccctttta gagaccgggg taaatttaaa aacactgctt gtgacatttg tggcaaaaca 3900 tttgcttgtc agagtgcctt ggacattcac tatagaagtc ataccaaaga gagaccattt 3960 atttgcacag tttgcaatcg tggcttttcc acaaagggta atttgaagca gcacatgttg 4020 acacatcaga tgcgagatct gccatcccag ctctttgagc ccagttccaa ccttggcccc 4080 aatcagaact cagcggtgat tcccgccaac tcgttgtcat ctctcatcaa gacagaggtc 4140 aacggcttcg tgcatgtttc tcctcaggac agtaaggaca cccccaccag tcacgtcccg 4200 tctgggcctc tgtcttcctc tgccacatcc ccagttctgc tccctgctct gcccaggaga 4260 actcccaagc agcactactg caacacatgt ggcaaaacct tctcctcatc gagtgccctg 4320 cagattcacg agagaactca cactggagag aaaccctttg cttgcactat ttgtggaaga 4380 gctttcacga ctaaaggcaa tcttaaggta cacatgggca ctcacatgtg gaatagcacc 4440 cctgcacgac ggggtcggcg gctctctgtg gatggcccca tgacatttct aggaggcaat 4500 cccgtcaagt tcccagaaat gttccagaag gatttggcgg caagatcagg aagtggggat 4560 ccttccagct tctggaatca gtatgcagca gcgctctcca acgggctggc gatgaaggcc 4620 aacgagatct ccgtcattca gaacggtggc atccctccaa ttcctggaag cctcggcagt 4680 gggaacagct cacctgttag tgggctgacg ggaaacctgg agaggctcca gaactcagag 4740 cccaatgctc ccctggccgg cctggagaaa atggcaagca gtgagaacgg aaccaacttc 4800 cgcttcaccc gcttcgtgga ggacagcaag gagatcgtca cgagttaa 4848 <210> 78 <211> 1083 <212> DNA <213> artificial sequence <220> <223> Oct4 CDS <400> 78 atggcgggac acctggcttc ggatttcgcc ttctcgcccc ctccaggtgg tggaggtgat 60 gggccagggg ggccggagcc gggctgggtt gatcctcgga cctggctaag cttccaaggc 120 cctcctggag ggccaggaat cgggccgggg gttgggccag gctctgaggt gtgggggatt 180 cccccatgcc ccccgccgta tgagttctgt ggggggatgg cgtactgtgg gccccaggtt 240 ggagtggggc tagtgcccca aggcggcttg gagacctctc agcctgaggg cgaagcagga 300 gtcggggtgg agagcaactc cgatggggcc tccccggagc cctgcaccgt cacccctggt 360 gccgtgaagc tggagaagga gaagctggag caaaacccgg aggagtccca ggacatcaaa 420 gctctgcaga aagaactcga gcaatttgcc aagctcctga agcagaagag gatcaccctg 480 ggatatacac aggccgatgt ggggctcacc ctgggggttc tatttgggaa ggtattcagc 540 caaacgacca tctgccgctt tgaggctctg cagcttagct tcaagaacat gtgtaagctg 600 cggcccttgc tgcagaagtg ggtggaggaa gctgacaaca atgaaaatct tcaggagata 660 tgcaaagcag aaaccctcgt gcaggcccga aagagaaagc gaaccagtat cgagaaccga 720 gtgagaggca acctggagaa tttgttcctg cagtgcccga aacccacact gcagcagatc 780 agccacatcg cccagcagct tgggctcgag aaggatgtgg tccgagtgtg gttctgtaac 840 cggcgccaga agggcaagcg atcaagcagc gactatgcac aacgagagga ttttgaggct 900 gctgggtctc ctttctcagg gggaccagtg tcctttcctc tggccccagg gccccatttt 960 ggtaccccag gctatgggag ccctcacttc actgcactgt actcctcggt ccctttccct 1020 gagggggaag cctttccccc tgtctccgtc accactctgg gctctcccat gcattcaaac 1080 tga 1083 <210> 79 <211> 918 <212> DNA <213> artificial sequence <220> <223> Nanog CDS <400> 79 atgagtgtgg atccagcttg tccccaaagc ttgccttgct ttgaagcatc cgactgtaaa 60 gaatcttcac ctatgcctgt gatttgtggg cctgaagaaa actatccatc cttgcaaatg 120 tcttctgctg agatgcctca cacggagact gtctctcctc ttccttcctc catggatctg 180 cttattcagg acagccctga ttcttccacc agtcccaaag gcaaacaacc cacttctgca 240 gagaagagtg tcgcaaaaaa ggaagacaag gtcccggtca agaaacagaa gaccagaact 300 gtgttctctt ccacccagct gtgtgtactc aatgatagat ttcagagaca gaaatacctc 360 agcctccagc agatgcaaga actctccaac atcctgaacc tcagctacaa acaggtgaag 420 acctggttcc agaaccagag aatgaaatct aagaggtggc agaaaaacaa ctggccgaag 480 aatagcaatg gtgtgacgca gaaggcctca gcacctacct accccagcct ttactcttcc 540 taccaccagg gatgcctggt gaacccgact gggaaccttc caatgtggag caaccagacc 600 tggaacaatt caacctggag caaccagacc cagaacatcc agtcctggag caaccactcc 660 tggaacactc agacctggtg cacccaatcc tggaacaatc aggcctggaa cagtcccttc 720 tataactgtg gagaggaatc tctgcagtcc tgcatgcagt tccagccaaa ttctcctgcc 780 agtgacttgg aggctgcctt ggaagctgct ggggaaggcc ttaatgtaat acagcagacc 840 actaggtatt ttagtactcc acaaaccatg gatttattcc taaactactc catgaacatg 900 caacctgaag acgtgtga 918 <210> 80 <211> 20 <212> DNA <213> artificial sequence <220> <223> SPI1 total forward primer <400> 80 ccccctccat cagaagacct 20 <210> 81 <211> 20 <212> DNA <213> artificial sequence <220> <223> SPI1 total reverse primer <400> 81 aagtcccagt aatggtcgct 20 <210> 82 <211> 20 <212> DNA <213> artificial sequence <220> <223> SPI1 endo forward primer <400> 82 cctgcaatgt caagggaggg 20 <210> 83 <211> 19 <212> DNA <213> artificial sequence <220> <223> SPI1 endo reverse primer <400> 83 ccaatgcaga gcccctcag 19 <210> 84 <211> 20 <212> DNA <213> artificial sequence <220> <223> CEBPB total forward primer <400> 84 gacgagtaca agatccggcg 20 <210> 85 <211> 20 <212> DNA <213> artificial sequence <220> <223> CEBPB total reverse primer <400> 85 acagctgctc caccttcttc 20 <210> 86 <211> 20 <212> DNA <213> artificial sequence <220> <223> CEBPB endo forward primer <400> 86 gggagcccgt cggtaatttt 20 <210> 87 <211> 20 <212> DNA <213> artificial sequence <220> <223> CEBPB endo reverse primer <400> 87 catgtgcggt tggtttggac 20

Claims (19)

  1. 줄기세포로부터 미세아교세포(microglia)를 생산하는 방법으로서,
    a) 전사 조절인자 단백질(transcriptional regulator protein)을 코딩하는(encoding) 뉴클레오티드 서열의 제1 게놈성 안전한 하버 부위(first genomic safe harbour site)로의 표적화된 삽입(targeted insertion) 단계; 및
    b) 전사 인자 PU.1의 코딩 서열(서열번호: 1)의 제2 게놈성 안전한 하버 부위로의 표적화된 삽입 단계로서, 여기서 유전자는 전사 조절인자 단백질에 의해 조절되는, 유도성 프로모터(inducible promoter)에 작동가능하게 연결되는 단계; PU.1(서열번호: 2)의 발현 단계; 및
    c) 단계 a) 및 b)로부터 받은 줄기 세포를 미세아교세포의 배아 발달 또는 성체 미세아교세포 증식, 분화 또는 분극화 중 적어도 한 단계 동안 신호전달(signaling)을 재연하는 적어도 하나의 성장 인자 또는 소분자에 노출시키면서 배양하는 단계
    를 포함하는, 줄기세포로부터 미세아교세포를 생산하는 방법.
  2. 제1항에 있어서, 적어도 하나의 성장 인자 또는 소분자가 액티빈 A(서열번호: 7), BMP4(서열번호: 8), FGF(서열번호: 9), VEGF-A(서열번호: 10), LY294002, CHIR99021, SCF(서열번호: 11), IL-3(서열번호: 12), IL-6(서열번호: 13), CSF1(서열번호: 14), IL-34(서열번호: 15), CSF2(서열번호: 16), CD200(서열번호: 17), CX3CL1(서열번호: 18), TGFβ1(서열번호: 19), 및 IDE1로 이루어진 군으로부터 선택되는 방법.
  3. 제1항 또는 제2항에 있어서, 적어도 하나의 성장 인자가 CSF1(서열번호: 14) 또는 IL-34(서열번호: 15)인 방법.
  4. 제1항 내지 제3항 중 어느 한 항에 있어서, 적어도 하나의 소분자가 CHIR99021, LY294002 또는 IDE1인 방법.
  5. 제1항 내지 제4항 중 어느 한 항에 있어서, 제1 및 제2 게놈성 안전한 하버 부위가 상이한 방법.
  6. 제1항 내지 제5항 중 어느 한 항에 있어서, 전사 인자 CEBPB의 유전자의 코딩 서열(서열번호: 3)의 삽입 및 이의 발현을 추가로 포함하는 방법..
  7. 제1항 내지 제6항 중 어느 한 항에 있어서, 전사 인자 RUNX1의 유전자의 코딩 서열(서열번호: 4)의 삽입 및 이의 발현을 추가로 포함하는 방법.
  8. 제1항 내지 제7항 중 어느 한 항에 있어서, 전사 인자 IRF8의 유전자의 코딩 서열(서열번호: 5)의 삽입 및 이의 발현을 추가로 포함하는 방법.
  9. 제1항 내지 제8항 중 어느 한 항에 있어서, 전사 인자 SALL1의 유전자의 코딩 서열(서열번호: 6)의 삽입 및 이의 발현을 추가로 포함하는 방법.
  10. 제1항 내지 제9항 중 어느 한 항에 있어서, 전사 조절인자 단백질이 역(reverse) 테트라시클린 전사활성인자(rtTA)(서열번호: 20)이고 이의 활성이 독시시클린 또는 테트라시클린에 의해 제어되는 방법.
  11. 제1항 내지 제10항 중 어느 한 항에 있어서, 유도성 프로모터가 Tet 반응성 요소(Tet Responsive Element; TRE)(서열번호: 21)를 포함하는 방법.
  12. 제1항 내지 제11항 중 어느 한 항에 있어서, 상기 제1 및 제2 게놈성 안전한 하버 부위가 hROSA26 유전자좌(locus)(서열번호: 22), AAVS1 유전자좌(서열번호: 23), CLYBL 유전자(서열번호: 24), CCR5 유전자(서열번호. 25), HPRT 유전자(서열번호. 26) 또는, 염색체 8 상의 부위 ID 325(서열번호: 27), 염색체 1 상의 부위 ID 227(서열번호: 28), 염색체 2 상의 부위 ID 229(서열번호: 29), 염색체 5 상의 부위 ID 225(서열번호: 30), 염색체 14 상의 부위 ID 259(서열번호: 31), 염색체 X 상의 부위 ID 263(서열번호: 32), 염색체 2 상의 부위 ID 303(서열번호: 33), 염색체 4 상의 부위 ID 231(서열번호: 34), 염색체 5 상의 부위 ID 315(서열번호: 35), 염색체 16 상의 부위 ID 307(서열번호: 36), 염색체 6 상의 부위 ID 285(서열번호: 37), 염색체 6 상의 부위 ID 233(서열번호: 38), 염색체 134 상의 부위 ID 311(서열번호: 39), 염색체 7 상의 부위 ID 301(서열번호: 40), 염색체 8 상의 부위 ID 293(서열번호: 41), 염색체 11 상의 부위 ID 319(서열번호: 42), 염색체 12 상의 부위 ID 329(서열번호: 43) 및 염색체 X 상의 부위 ID 313(서열번호: 44)을 가진 유전자로 이루어진 군으로부터 선택되는 방법.
  13. 제1항 내지 제12항 중 어느 한 항에 있어서, 상기 줄기 세포가 만능 줄기 세포, 유도 만능 줄기 세포(iPSC), 신경 전구 세포(neural progenitor cell), 조혈 줄기 세포 또는 배아 줄기 세포(ESC)인 방법.
  14. 제1항 내지 제13항 중 어느 한 항에 있어서, 상기 줄기 세포가 인간 또는 마우스 줄기 세포인 방법.
  15. 제1항 내지 제14항 중 어느 한 항에 따른 방법 중 어느 하나에 의해 수득된 미세아교세포로서, 바람직하게는 ITGAM(CD11B)(서열번호: 45), ITGAX(CD11C)(서열번호: 46), CD14(서열번호: 47), CD16(서열번호: 48), ENTPD1(CD39)(서열번호: 49), PTPRC(CD45)(서열번호: 50), CD68(서열번호: 51), CSF1R(CD115)(서열번호: 52), CD163(서열번호: 53), CX3CR1(서열번호: 54), TREM2(서열번호: 55), P2RY12(서열번호: 56), TMEM119(서열번호: 57), 및 HLA-DR(서열번호: 58)로 이루어진 군으로부터 선택된 적어도 하나의 미세아교세포 표면 단백질을 발현하는 미세아교세포.
  16. 제15항에 있어서, 요법(therapy)에서 사용하기 위한 미세아교세포.
  17. 질환의 시험관내 진단을 위한, 제15항 또는 제16항에 따른 미세아교세포의 용도.
  18. 제17항에 있어서, 질환이 중추신경계 질환(disease of the central nervous system), 바람직하게는 신경퇴행성 질환(neurodegenerative disease); 보다 바람직하게는 알츠하이머병(Alzheimer's disease), 파킨슨병(Parkinson's disease), 전두측두엽 치매(frontotemporal dementia) 또는 근위축성 측삭 경화증(Amyotrophic Lateral Sclerosis); 신경염증성 또는 자가면역 질환(neuroinflammatory or autoimmune disease), 바람직하게는 다발성 경화증(Multiple Sclerosis), 자가-항체-매개 뇌염(auto-antibody-mediated encephalitis) 또는 감염성 질환(infectious disease), 신경혈관 질환(neurovascular disease); 바람직하게는 뇌졸중(stroke), 혈관염(vasculitis); 외상성 뇌 손상(traumatic brain injury), 및 암(cancer)의 질환으로 이루어진 군으로부터 선택되는 미세아교세포의 용도.
  19. 뇌 오가노이드(brain organoid)를 사용한 시험관내 배양을 위한, 제15항 또는 제16항에 따른 미세아교세포의 용도.
KR1020217040483A 2019-05-27 2020-05-27 인간 만능 줄기 세포로부터 미세아교세포의 신속하고 결정적인 생성 KR20220013556A (ko)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
EP19176722.7 2019-05-27
EP19176722 2019-05-27
PCT/EP2020/064649 WO2020239807A1 (en) 2019-05-27 2020-05-27 Rapid and deterministic generation of microglia from human pluripotent stem cells

Publications (1)

Publication Number Publication Date
KR20220013556A true KR20220013556A (ko) 2022-02-04

Family

ID=66655224

Family Applications (1)

Application Number Title Priority Date Filing Date
KR1020217040483A KR20220013556A (ko) 2019-05-27 2020-05-27 인간 만능 줄기 세포로부터 미세아교세포의 신속하고 결정적인 생성

Country Status (11)

Country Link
US (1) US20220220441A1 (ko)
EP (1) EP3976766A1 (ko)
JP (1) JP2022534260A (ko)
KR (1) KR20220013556A (ko)
CN (1) CN114174523A (ko)
AU (1) AU2020281762A1 (ko)
BR (1) BR112021023618A2 (ko)
CA (1) CA3139235A1 (ko)
MX (1) MX2021014456A (ko)
SG (1) SG11202112475QA (ko)
WO (1) WO2020239807A1 (ko)

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2023282290A1 (ja) * 2021-07-06 2023-01-12 慶應義塾 ミクログリア前駆細胞並びにミクログリア製造方法、製造されたミクログリア前駆細胞及びミクログリア
WO2023102471A1 (en) * 2021-12-01 2023-06-08 Yale University Human cortical organoids with engineered microglia-like cells
WO2023135318A1 (en) * 2022-01-17 2023-07-20 Westfälische Wilhelms-Universität Münster Method for expression of a transgene of interest from neural precursor cells
JP2023140135A (ja) * 2022-03-22 2023-10-04 株式会社リコー ミクログリアの製造方法

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2016210313A1 (en) * 2015-06-24 2016-12-29 Whitehead Institute For Biomedical Research Culture medium for generating microglia from pluripotent stem cells and related methods
CA3016575A1 (en) * 2016-03-03 2017-09-08 New York Stem Cell Foundation, Inc. Microglia derived from pluripotent stem cells and methods of making and using the same
US11345891B2 (en) * 2017-04-05 2022-05-31 Asgard Therapeutics Ab Compositions for reprogramming cells into dendritic cells or antigen presenting cells, methods and uses thereof
US20200063105A1 (en) * 2017-05-01 2020-02-27 President And Fellows Of Harvard College Transcription factors controlling differentiation of stem cells
CN110205295B (zh) * 2019-06-25 2021-10-29 中国科学院动物研究所 一种多能干细胞诱导产生小胶质细胞的方法及试剂盒
WO2023282290A1 (ja) * 2021-07-06 2023-01-12 慶應義塾 ミクログリア前駆細胞並びにミクログリア製造方法、製造されたミクログリア前駆細胞及びミクログリア

Also Published As

Publication number Publication date
CN114174523A (zh) 2022-03-11
US20220220441A1 (en) 2022-07-14
EP3976766A1 (en) 2022-04-06
JP2022534260A (ja) 2022-07-28
AU2020281762A1 (en) 2021-12-02
CA3139235A1 (en) 2020-12-03
MX2021014456A (es) 2022-01-06
BR112021023618A2 (pt) 2022-04-12
WO2020239807A1 (en) 2020-12-03
SG11202112475QA (en) 2021-12-30

Similar Documents

Publication Publication Date Title
AU2022201329B2 (en) Genetically modified cells, tissues, and organs for treating disease
AU2023274083A1 (en) Compositions and methods for treating non-age-associated hearing impairment in a human subject
KR101999410B1 (ko) 염색체 랜딩 패드 및 관련된 용도
KR20220013556A (ko) 인간 만능 줄기 세포로부터 미세아교세포의 신속하고 결정적인 생성
KR20220002609A (ko) 포유동물 세포의 특성을 변경하기 위한 인공 마이크로-rna 및 이들 생성물의 조성물을 사용한 포유동물 세포의 변형
WO2020097372A1 (en) Use of adeno-associated viral vectors to correct gene defects/ express proteins in hair cells and supporting cells in the inner ear
KR20200126997A (ko) 인간 대상체에서의 비-노화-관련 청각 손상의 치료를 위한 조성물 및 방법
KR20210138587A (ko) 개선된 면역요법을 위한 조합 유전자 표적
KR20170086027A (ko) 신경발달 장애에서의 행동을 개선시키기 위한 박테리아를 포함하는 조성물 및 방법
KR20220098384A (ko) 폼페병 및 리소좀 장애를 치료하기 위한 간-특이적 프로모터를 포함하는 치료적 아데노-관련 바이러스
AU2023202878A1 (en) Methods for targeted insertion of DNA in genes
AU2022200784B2 (en) Non-human animal exhibiting diminished upper and lower motor neuron function and sensory perception
KR20230034198A (ko) 종양 침윤 림프구의 활성화 및 확장 방법
CN115003387A (zh) 用于活化和扩增肿瘤浸润淋巴细胞的方法
KR20210088605A (ko) 유전 장애에 대한 유전자 발현을 변경하는 방법
KR20220157944A (ko) 인간 대상체에서 비-연령-연관 청각 장애를 치료하기 위한 조성물 및 방법
US20220395582A1 (en) Compositions and methods of inducing differentiation of a hair cell
WO2018209358A2 (en) Systemic delivery of polypeptides
CN116157522A (zh) A1cf抑制剂用于治疗乙型肝炎病毒感染的用途
EA046478B1 (ru) Быстрая и детерминистическая генерация микроглии из плюрипотентных стволовых клеток человека
CN113817770B (zh) Cd73基因人源化的非人动物的构建方法及应用
TW202305132A (zh) 用於抑制α-突觸核蛋白表達之反義寡核苷酸
KR20230173074A (ko) 향상된 이종이식편 생존 및 관용을 위한 하나 이상의 변형된 유전자를 갖는 세포, 조직, 기관, 및 동물