PT1939287T

PT1939287T - Método de transferência de genes específico para células trofectodérmicas

Info

Publication number: PT1939287T
Application number: PT67819805T
Authority: PT
Inventors: Okabe Masaru; Ikawa Masahito
Original assignee: Fuso Pharmaceutical Ind; Okabe Masaru; Ikawa Masahito
Priority date: 2005-08-12
Filing date: 2006-07-31
Publication date: 2017-02-03
Also published as: EP1939287A1; US8815598B2; EP1939287B1; JP5020083B2; US20090013418A1; EP1939287A4; WO2007020786A1; US20140370602A1; ES2606912T3; JPWO2007020786A1; DK1939287T3

Description

DESCRIÇÃO

"MÉTODO DE TRANSFERENCIA DE GENES ESPECÍFICO PARA CÉLULAS TROFECTODÉRMICAS"

Campo Técnico A presente invenção refere-se a métodos de introdução de polinucleótidos arbitrários especificamente numa célula trofectodérmica não humana. A presente invenção refere-se também a métodos de produção de um blastocisto não humano compreendendo uma célula trofectodérmica especificamente introduzida com um polinucleótido arbitrário. Técnica Anterior

Os métodos de produção de ratinhos transgénicos utilizando vetores retrovirais (Documento 1 não de patente) são conhecidos como métodos de introdução de genes ao nível individual utilizando vetores virais. Os ratinhos transgénicos podem ser produzidos eficazmente utilizando vetores retrovirais; contudo, uma desvantagem é que ocorre silenciamento da expressão de genes como consequência da metilação dos genes introduzidos, ou semelhantes (Documento 2 não de patente).

Pode esperar-se a expressão a longo prazo de genes introduzidos com o vetor lentiviral o qual é um vetor retroviral, porque este permite a integração de genes estranhos no cromossoma. Além disso, ao contrário dos vetores retrovirais típicos, os vetores lentivirais têm um sinal de translocação nuclear, e podem assim introduzir genes em células que não estão em divisão. Quando os ratinhos transgénicos são produzidos utilizando vetores lentivirais, a eficiência de produção aumenta e não ocorre silenciamento de genes na expressão de genes a longo prazo (Documentos 3 a 5 não de patentes).

Nestes métodos de produção de ratinhos transgénicos, os genes são introduzidos na maioria dos óvulos fertilizados infetados com o vetor virai. Além disso, estes métodos introduzem genes na placenta e no embrião, e são assim consideradas como técnicas muito excelentes em estudos de desenvolvimento.

[Documento 1 não de patente] Proc. Natl. Acad. Sei. USA., 1985, set; 82(18): 6148-6152 [Documento 2 não de patente] Proc. Natl. Acad. Sei. USA., 1985, out; 82(20): 6927-6931 [Documento que não é de patente 3] Mol. Cell. Biol., 2000, out; 20 (20) : 7419-7426 [Documento 4 não de patente] J. Virol., 2000, nov; 74(22): 10778-10784 [Documento 5 não de patente] Proc. Natl. Acad. Sei. USA., 2002, 19 fev; 99(4): 2140-2145

Divulgação da Invenção [Problemas a serem Resolvidos pela Invenção]

Para analisar a expressão de genes na placenta e os seus efeitos durante a embriogénese, devem ser introduzidos genes estranhos, não só, na placenta mas também no embrião. Um método convencional para introduzir genes na placenta compreende a injeção direta de um vetor virai ou semelhante na placenta utilizando uma agulha de injeção ou semelhante após laparotomia durante a gravidez. No entanto, as desvantagens do método são o grande esforço imposto pela cirurgia e o facto de não ser espectável que o método introduza genes em toda a área da placenta.

Além disso, como métodos baseados em LV para a introdução de genes na placenta são conhecidos um método transgénico que utiliza a infeção de óvulos fertilizados (embriões do passo de duas células) e um método de microinjeção na cavidade do blastocisto. 0 primeiro método tem a vantagem de a operação ser conveniente e a desvantagem dos genes serem introduzidos na placenta e no embrião.

Entretanto, embora o último método de microinjeção na cavidade do blastocisto permita que os genes sejam especificamente introduzidos na placenta, este não é geralmente utilizado porque o método requer um sistema dispendioso e técnicas engenhosas. Além disso, o método é problemático na medida em que os embriões são muito danificados porque é diretamente introduzido um capilar de vidro nos blastocistos.

Além disso, é difícil tratar embriões numa grande escala por este método.

Existe também um método conhecido para preparar animais resgatados da letalidade embrionária devido a anormalidade placentária, e baseia-se num método de resgate tetraploide. Neste método, além de um mutante animal, são preparados embriões do passo de duas células de um animal de tipo selvagem e, em seguida, fundidos em conjunto para preparar embriões tetraploides por tratamento elétrico ou semelhante. Em seguida, são preparados embriões quiméricos agregando embriões do passo de oito células do animal mutante com os embriões do passo de quatro células tetraploides do animal de tipo selvagem, de ambos os quais foi removida a zona pelúcida. Os animais quiméricos são gerados transplantando os embriões quiméricos em animais pseudográvidos.

No entanto, as experiências que utilizam este método são também demoradas, porque o método requer embriões de um animal de tipo selvagem além daqueles de um animal mutante. Além disso, os embriões de tipo selvagem devem ser tetraploidizados por fusão elétrica ou semelhante. Além disso, o método é utilizado para complementar a função placentária em animais mutantes e não é assim adequado para analisar a função de genes na placenta. A presente invenção foi realizada tendo em consideração as circunstâncias anteriores. Um objetivo da presente invenção é proporcionar métodos de introdução de genes especificamente em toda a placenta.

[Meios para Resolver os Problemas]

As presentes requerentes realizaram vários exames para conseguir o objetivo descrito acima. Como consequência, as requerentes determinaram que poderiam ser introduzidos especificamente genes em células trofectodérmicas com alta eficiência, infetando blastocistos não humanos, dos quais foi removida a zona pelúcida (matriz extracelular que cobre os embriões iniciais pré-implantação para protegê-los de infeção virai e semelhantes), com vetores virais.

Mais especificamente, as presentes requerentes introduziram com sucesso, genes na trof ectoderme não humana, a qual é a camada externa do blastocisto, removendo a zona pelúcida com tratamento ácido, tratamento enzimático ou tratamento físico, e cocultivando blastocistos não humanos com vetores virais. Deste modo, as requerentes realizaram a presente invenção. Além disso, as requerentes determinaram que este método não tem qualquer risco de infetar células da massa celular interna não humana, a qual se transforma num feto não humano no futuro, com o vetor virai porque a trofectoderme serve como uma barreira. Especificamente, a presente invenção proporciona o seguinte: 1. Um método para introduzir um polinucleótido arbitrário especificamente numa célula trofectodérmica não humana, o qual compreende os passos de: (a) remover a zona pelúcida de um blastocisto não humano; e (b) introduzir um polinucleótido arbitrário nas células trofectodérmicas do blastocisto obtido no passo (a). 2. Um método de produção de um blastocisto não humano compreendendo uma célula trofectodérmica especificamente introduzida com um polinucleótido arbitrário, o qual compreende os passos de: (a) remover a zona pelúcida de um blastocisto não humano; e (b) introduzir um polinucleótido arbitrário nas células trofectodérmicas do blastocisto obtido no passo (a). 3. 0 método do item 1 ou 2, em que o polinucleótido arbitrário é um polinucleótido que codifica uma proteína essencial para o desenvolvimento fetal ou um polinucleótido que regula a expressão da proteína. 4. 0 método do item 3, em que o polinucleótido que codifica uma proteína essencial para o desenvolvimento fetal é, pelo menos, um polinucleótido selecionado do grupo consistindo em: Dlx3, Fgfr2, Fral, Fzd5, Gabl, Gcml, hipomorfo Grb2, Gja7, Hgf, Hsp84-1, Itgav, Junb, Lifr, ERK1, ERK2, ERK5, MEK1, MEKk3, ρ38α, ρ38β, Met, Pdgfra, Pdgfb, Pparg, Rxra,

Rxrb, Sosl, Vhlh, Wnt2, Ets2, Mash2, Egfr, Hsfl, Bmp5,

Bmp7, Dnmtl, Itga4, Lhxl, Mrj, Tcf, Lef, Cdx2, Eomes, Fgf4,

Esrrb, Handl, Mdfi, Esxl, Arnt, Tcfeb e Gjb2. 5. 0 método de qualquer um dos itens 1 a 4, em que o blastocisto é derivado de um animal não humano que tem anormalidade numa proteína essencial para o desenvolvimento fetal ou na regulação da expressão da proteína. 6. 0 método de qualquer um dos itens 1 a 5, em que a zona pelúcida é removida por tratamento ácido, tratamento enzimático ou tratamento físico. 7. 0 método do item 6, em que o tratamento ácido é um tratamento com solução de Tyrode ácida. 8. 0 método do item 6, em que o tratamento enzimático é um tratamento com pronase. 9. 0 método de qualquer um dos itens 1 a 8, em que o polinucleótido é introduzido infetando um blastocisto com um vetor virai portador de um polinucleótido desejado. 10. O método de qualquer um dos itens 1 a 8, em que o polinucleótido é introduzido utilizando um reagente de transfeção de ácido nucleico.

Breve Descrição dos Desenhos A Fig. 1 é um diagrama que mostra a estrutura do vetor LV (LV-CAG-EGFP) utilizado na presente invenção. A Fig. 2 mostra fotografias de fetos e placentas de embriões E13.5 obtidos por infeção com um vetor virai que expressa EGFP. Os respetivos fetos e placentas são: derivados de embrião não tratado (superior); obtidos pelo método TG (central); obtido pelo método da presente invenção (inferior). No método da presente invenção, a expressão do gene introduzido ocorre apenas na placenta, enquanto no método TG, a expressão de genes é observada no feto e na placenta. A Fig. 3 mostra fotografias de secções de placentas de embriões E13.5 obtidos por infeção com um vetor virai que expressa EGFP. As respetivas secções finas de placenta são: derivadas de embrião não tratado (superior); obtidas pelo método TG (central); obtidas pelo método da presente invenção (inferior). Na placenta tratada pelo método TG e o método da presente invenção, foi observada expressão de genes em quase todas as células, exceto nas células maternais, na camada de células gigantes, camada de espongiotrofoblastos e camada labiríntica. a é uma fotografia após revelação com HE; b é uma fotografia através de microscópio fluorescente. A Fig. 4 mostra diagramas e fotografias que ilustram o resgate de ratinhos com gene erk2 inativado. a é um diagrama que ilustra o lócus em ratinhos com gene erk2 inativado. A erk endógena não é expressa, porque um gene de resistência a fármacos é inserido entre os exões 2 e 3. b é um diagrama que mostra um vetor lentiviral construído para expressar erk2 sob o controlo de um promotor CAG. c é um diagrama que mostra os genótipos de descendentes obtidos utilizando o método da presente invenção para transferir genes para blastocistos obtidos por acasalamento de ratinhos heterozigóticos. Os ratinhos homozigóticos não nascem por acasalamento natural; contudo, 16 ratinhos homozigóticos foram obtidos pelo método de transferência de genes específicos para a placenta da presente invenção, d é uma fotografia que mostra a genotipagem por PCR dos descendentes obtidos. Nasceram ratinhos homozigóticos que tinham apenas o alelo mutante, mas nenhum alelo de tipo selvagem, e é uma fotografia que mostra ratinho erk2 de tipo selvagem (esquerda) , ratinho heterozigótico (centro) e ratinho recém-nascido homozigótico (direita) nascido como consequência do tratamento da presente invenção, f é uma fotografia que mostra o resultado da transferência de Western. Foi demonstrado que o recém-nascido expressava erk2 endógena e os ratinhos homozigóticos não expressavam erk2 . A Fig. 5 mostra diagramas e fotografias que ilustram o resgate de ratinhos com o gene p38a inativado. a é um diagrama que ilustra o lócus em ratinhos com o gene p38a inativado. A p38a endógena não é expressa, porque um gene de resistência a fármacos é inserido entre os exões 10 e 11. b é um diagrama que mostra um vetor lentiviral construído para expressar p38a sob o controlo de um promotor CAG. c é uma fotografia que mostra os genótipos de descendentes obtidos utilizando o método da presente invenção para transferir genes para blastocistos obtidos por acasalamento de ratinhos heterozigóticos. Os ratinhos homozigóticos não nascem por natural acasalamento; contudo, 34 ratinhos homozigóticos foram obtidos pelo método de transferência de genes específicos para a placenta da presente invenção. d é uma fotografia que mostra a genotipagem por PCR dos descendentes obtidos. Nasceram ratinhos homozigóticos tendo apenas o alelo mutante mas nenhum alelo de tipo selvagem, e é uma fotografia que mostra o ratinho p38a de tipo selvagem (esquerda) , e ratinho recém-nascido homozigótico (direita) nascido como consequência do tratamento da presente invenção, f é uma fotografia que mostra o resultado de transferência de Western. Foi demonstrado que o recém-nascido expressava p38a endógena e os ratinhos homozigóticos não expressavam erk2.

Melhor Modo para Realizar a Invenção A presente invenção baseia-se na constatação pelas presentes requerentes que genes arbitrários podem ser introduzidos especificamente em células trofectodérmicas não humanas com alta eficiência, infetando vetores virais portadores de um polinucleótido arbitrário em blastocistos não humanos, dos quais foi removida a zona pelúcida (matriz extracelular que cobre os embriões iniciais pré-implantação para protegê-los de infeção virai, e semelhantes), com vetores virais. Mais especificamente, a presente invenção refere-se a métodos de introdução de polinucleótidos arbitrários especificamente nas células trofectodérmicas não humanas.

Nos métodos da presente invenção, em primeiro lugar, são obtidos blastocistos não humanos. Blastocisto refere-se a um embrião que terminou o passo de segmentação durante o desenvolvimento fetal mamífero inicial. Os óvulos de mamífero são alecíticos; estes dividem-se holoblasticamente e formam agregados de blastómeros. No passo de 32 células, os ovos encontram-se divididos na trofectoderme que envolve o exterior do agregado e a massa celular interna dentro do agregado. A massa celular interna transforma-se no corpo de um feto no futuro, enquanto a trofectoderme diferencia-se na placenta. Nos métodos da presente invenção, os polinucleótidos arbitrários são introduzidos especificamente nas células trofectodérmicas não humanas que constituem a camada mais externa de um blastocisto.

Os blastocistos não humanos podem ser preparados pelos métodos descritos abaixo. Especificamente, os óvulos e espermas são recolhidos de animais arbitrários e, em seguida, é realizada a fertilização por métodos conhecidos dos especialistas na técnica. Os blastocistos não humanos podem ser preparados a partir dos óvulos fertilizados resultantes por métodos conhecidos dos especialistas na técnica, por exemplo, por cultura dos óvulos em meio kSOM durante 96 horas. Alternativamente, os blastocistos não humanos podem ser obtidos diretamente a partir de animais de acordo com métodos que são convencionalmente utilizados pelos especialistas na técnica (por exemplo, métodos descritos em: Manipulating the mouse embryo, a laboratory manual, 3a edição, p201-203, Cold Spring Harbor Laboratory Press).

Nos métodos da presente invenção, a zona pelúcida é, em seguida, removida dos blastocistos não humanos obtidos acima. Os embriões (embriões iniciais pré-implantação) estão cobertos com a zona pelúcida, a qual é a matriz extracelular, para protegê-los da infeção por vírus, ou semelhantes. Nos métodos da presente invenção, a zona pelúcida é removida. A zona pelúcida pode ser removida por métodos conhecidos, por exemplo, tratamento ácido, tratamento enzimático ou tratamento físico. Um exemplo de tal tratamento ácido é um tratamento que utiliza solução de Tyrode ácida (Manipulating the mouse embryo, a laboratory manual, 3â edição, p485-486, Cold

Spring Harbor Laboratory Press). A zona pelúcida pode ser parcialmente dissolvida, por exemplo, aspirando a solução de Tyrode ácida (pH 2,3 a 2,5) com um micropipeta e, em seguida, pulverizando suavemente os embriões não humanos imobilizados com a solução. Alternativamente, a zona pelúcida pode ser dissolvida imergindo os embriões não humanos em solução de Tyrode ácida. 0 tratamento enzimático para remover a zona pelúcida inclui o tratamento com pronase (Calbiochem 537088, Sigma P5147) e semelhantes. Por exemplo, os embriões não humanos são colocados numa solução de pronase a 0,5% até a zona pelúcida se dissolver. Depois de a zona pelúcida se dissolver, os embriões são bem lavados com um meio e, em seguida, podem ser obtidos os blastocistos com a zona pelúcida removida (Manipulating the mouse embryo, a laboratory manual, 3â edição, p731, Cold Spring Harbor Laboratory Press).

Além disso, na presente invenção, a zona pelúcida pode ser também removida por métodos físicos. Tais métodos físicos de remoção incluem um método de dissecção da zona pelúcida em que os embriões não humanos são imobilizados e parte da zona pelúcida é dissecada com uma micropipeta (Hum. Reprod., 5:7-13, 1990), métodos para dissecção, perfuração ou adelgaçamento da zona pelúcida com um laser (Hum. Reprod., 15:1061-1064, 2000) ou micromanipulador piezoelétrico (Developmental Biology, 250:348-357, 2002), e semelhantes. A zona pelúcida pode ser removida pelos métodos descritos acima. Na presente invenção, contudo, os métodos para remover a zona pelúcida não se encontram limitados aos exemplos descritos acima, e os métodos incluem todos os métodos que possam remover a zona pelúcida.

Nos métodos da presente invenção, finalmente, os polinucleótidos arbitrários são introduzidos nos blastocistos não humanos com a zona pelúcida removida. Numa forma de realização preferida, os métodos de introdução de polinucleótidos arbitrários nos blastocistos não humanos com a zona pelúcida removida, incluem métodos de introdução de um vetor portador de um polinucleótido arbitrário nos blastocistos, mas não estão particularmente limitados a estes.

Os vetores portadores de um polinucleótido arbitrário a ser introduzido nos blastocistos não humanos incluem vetores virais. Tais vetores virais incluem vetores virais arbitrários convencionalmente utilizados pelos especialistas na técnica, por exemplo, vetores lentivirais (Molecular Therapy 2003, 8; 666-673), vetores retrovirais (Molecular Therapy 2003, 8; 666-673), vetores de adenovirus, lipossomas de HVJ, Lipofectamina, e semelhantes. O lipossoma de HVJ (vírus hemaglutinante do Japão: vírus Sendai) é um vetor que pode introduzir eficazmente genes e oligonucleótidos encapsulados em lipossomas em vários órgãos do corpo utilizando a atividade da proteína de fusão de HVJ, um vírus que origina fusão celular, e HMG-1, uma proteína de ligação a ADN.

Entre tais vetores, os vetores lentivirais são preferidos. O lentivírus pertence à família de retrovirus e é um vírus da imunodeficiência em humanos, macacos, gatos e bovinos. No que se refere à estrutura de genes, o vírus é constituído por vários genes reguladores além de genes estruturais fundamentais para o retrovirus (gag, pol e env). Os vetores lentivirais construídos alterando o lentivírus podem integrar genes estranhos no cromossoma e, desse modo, pode esperar-se expressão a longo prazo dos genes introduzidos nestes. Além disso, ao contrário de outros vetores retrovirais, os vetores lentivirais têm um sinal de translocação nuclear e, desse modo, podem introduzir genes em células que não estão em divisão.

Os vetores lentivirais utilizados na presente invenção incluem vetores lentivirais que têm pelo menos LTR, RRE e GAG. Os vetores lentivirais utilizados nos métodos da presente invenção devem ter, pelo menos, estes requisitos, mas podem ter adicionalmente outros genes, por exemplo, deltaU3, PPT e WPRE. Tais vetores lentivirais são também, de um modo preferido, utilizados como o vetor virai nos métodos da presente invenção.

Numa forma de realização particularmente preferida, os vetores lentivirais utilizados na presente invenção têm LTR (deltaU3) , GAG, RRE, PPT e WPRE. Um exemplo representativo de vetores lentivirais que têm tais estruturas é um vetor construído substituindo um ADNc de interesse pela unidade de GFP do vetor virai de GFP divulgado no Exemplo 1 e no seguinte documento: Molecular Therapy 2003, 8; 666-673. A estrutura e o método de construção do vetor são divulgados no documento indicado acima.

Os blastocistos não humanos podem ser infetados com um vetor lentiviral portador de um polinucleótido arbitrário, por exemplo, misturando blastocistos com a zona pelúcida removida com uma solução que contém o vetor lentiviral portador do polinucleótido arbitrário e, em seguida, deixando a mistura em repouso durante 4 a 5 horas. Através deste método, um vetor lentiviral tendo um polinucleótido arbitrário pode ser especificamente introduzido na trofectoderme.

Alternativamente, os polinucleótidos arbitrários podem ser também introduzidos em blastocistos não humanos com a zona pelúcida removida utilizando um reagente de transfeção de ácido nucleico. Aqui, o reagente de transfeção de ácido nucleico refere-se a qualquer reagente que possa introduzir um polinucleótido arbitrário nos blastocistos. Tais reagentes de transfeção de ácido nucleico incluem, mas não estão limitados a, por exemplo, Lipofectamina 2000 (Invitrogen), Effectene (Qiagen) e FuGene (Roche) .

Um polinucleótido a ser introduzido pode estar numa forma, tais como ADN, ARN, ADNc, ARNm, ou ácido nucleico artificial. Tais ADN, ARN, ADNc e ARNm incluem também os seus derivados. Tais ácidos nucleicos artificiais incluem, mas não estão limitados a, por exemplo, ADN, ARN, ADNc, ARNm, em que as suas estruturas de cadeias de açúcar são modificadas, ou seus derivados. Além disso, os polinucleótidos a serem introduzidos podem ser polinucleótidos nus ou polinucleótidos introduzidos num vetor. Os especialistas na técnica podem conceber e utilizar vetores apropriados dependendo do objetivo. Os vetores utilizados na presente invenção podem compreender, além de um polinucleótido arbitrário a ser introduzido, regiões polinucleótidicas que funcionam em hospedeiros de expressão, tais como sítio de iniciação da transcrição e sítio de terminação da transcrição, para uma expressão mais eficiente do polinucleótido arbitrário.

Numa forma de realização preferida da presente invenção, os polinucleótidos a serem introduzidos incluem, mas não estão particularmente limitados a, polinucleótidos que codificam uma proteína essencial para o desenvolvimento fetal ou polinucleótidos que regulam a expressão de uma proteína essencial para o desenvolvimento fetal.

Tais polinucleótidos que codificam uma proteína essencial para o desenvolvimento fetal incluem quaisquer polinucleótidos que codificam uma proteína direta ou indiretamente envolvida no desenvolvimento fetal. Tais polinucleótidos incluem, mas não estão limitados a, por exemplo, Dlx3 (SEQ ID N2 : 1), Fgfr2 (SEQ ID N2: 2), Fral (SEQ ID N2 : 3), Fzd5 (SEQ ID N2 : 4), Gabl (SEQ ID N2: 5), Gcml (SEQ ID N2: 6), hipomorfo Grb2 (SEQ ID N2: 7), Gja7 (SEQ ID N2: 8), Hgf (SEQ ID N2: 9), Hsp84-1 (SEQ ID N2: 10), Itgav (SEQ ID N2 : 11), Junb (SEQ ID N2 : 12),

Lifr (SEQ ID N2 : 13), ERK1 (SEQ ID N2 : 14), ERK2 (SEQ ID N2: 15), ERK5 (SEQ ID N2: 16), MEK1 (polinucleótido que codifica a sequência de aminoácidos de SEQ ID N2: 17), MEKk3 (polinucleótido que codifica a sequência de aminoácidos de SEQ ID N2: 18), p38a (SEQ ID N2 : 19), ρ38β (SEQ ID N2 : 20), Met (SEQ ID N2: 21), Pdgfra (SEQ ID N2: 22), Pdgfb (SEQ ID N2: 23),

Pparg (SEQ ID N2 : 24), Rxra (SEQ ID N2: 25), Rxrb (SEQ ID N2: 26), Sosl (SEQ ID N2: 27), Vhlh (SEQ ID N2: 28),

Wnt2 (SEQ ID N2 : 29), Ets2 (SEQ ID N2: 30), Mash2 (SEQ ID N2: 31), Egfr (SEQ ID N2: 32), Hsfl (SEQ ID N2: 33),

Bmp5 (SEQ ID N2 : 34), Bmp7 (SEQ ID N2: 35), Dnmtl (SEQ ID N2: 36), Itga4 (SEQ ID N2 : 37), Lhxl (SEQ ID N2 : 38),

Mrj (SEQ ID N2: 39), Tcfl (SEQ ID N2: 40), Lefl (SEQ ID N2: 41), Cdx2 (SEQ ID N2: 42), Eomes (SEQ ID N2 : 43), Fgf4 (SEQ ID N2: 44), Esrrb (SEQ ID N2 : 45), Handl (SEQ ID N2 : 46),

Mdfi (SEQ ID N2: 47), Esxl (SEQ ID N2: 48), Arnt (SEQ ID N2: 49), Tcfeb (SEQ ID N2: 51) e Gjb (SEQ ID N2: 52).

Os especialistas na técnica podem obter facilmente os polinucleótidos descritos acima que codificam uma proteína essencial para o desenvolvimento fetal. Por exemplo, tais polinucleótidos podem ser isolados a partir de fontes naturais, utilizando várias amostras biológicas, tais como tecidos placentários, células estaminais de trofoblastos e células diferenciadas das mesmas como uma fonte, com base nas suas propriedades físico-químicas, e semelhantes. Alternativamente, os polinucleótidos podem ser quimicamente sintetizados com base na informação conhecida sobre a sequência. Alternativamente, os polinucleótidos podem ser obtidos utilizando técnicas de recombinação de genes para transformar células hospedeiras com um vetor portador de polinucleótidos que codificam uma proteína essencial para o desenvolvimento fetal, cultivando, em seguida, as células transformadas resultantes que produzam a proteína recombinante do gene, e recolhendo a proteína a partir das células ou do seu sobrenadante de cultura.

Os polinucleótidos supramencionados que codificam uma proteína essencial para o desenvolvimento fetal incluem genes homólogos de vários animais. Aqui, "gene homólogo" refere-se aos polinucleótidos listados acima das SEQ ID N2: 1 a 16 e 19 a 51, polinucleótidos que codificam uma proteína que compreende a sequência de aminoácidos da SEQ ID N2: 17 ou 18, ou polinucleótidos que codificam uma proteína tendo uma função biológica equivalente àquela dos produtos de transcrição/tradução de tais polinucleótidos, em vários animais.

Os métodos que são bem conhecidos dos especialistas na técnica para isolar genes homólogos incluem técnicas de hibridação (Southern, E. M., Journal of Molecular Biology, Vol. 98, 503, 1975) e técnicas de reação em cadeia da polimerase (PCR) (Saiki, R. K., et al. Science, vol. 230, 1350-1354, 1985,

Saiki, R. K. et al. Science, vol. 239, 487-491, 1988) . Mais especificamente, os especialistas na técnica podem isolar rotineiramente os polinucleótidos que codificam uma proteína essencial para o desenvolvimento fetal a partir de várias células e tecidos animais (por exemplo, tecidos placentários, células estaminais de trofoblastos e células diferenciadas das mesmas), utilizando como uma sonda, polinucleótidos que codificam uma proteína essencial para o desenvolvimento fetal (por exemplo, as sequências polinucleotídicas das SEQ ID P: la 16 e 19 a 51, e as sequências polinucleotídicas que codificam uma proteína que compreende a sequência de aminoácidos das SEQ ID N2: 17 ou 18) ou uma sua porção, ou utilizando como um iniciador, oligonucleótidos que hibridizam especificamente com os polinucleótidos que codificam uma proteína essencial para o desenvolvimento fetal. Alternativamente, as sequências de genes homólogos podem ser obtidas a partir de bases de dados conhecidas.

Os polinucleótidos da presente invenção que codificam uma proteína essencial para o desenvolvimento fetal são, de um modo preferido, derivados de, mas não estão particularmente limitados a, humanos, ratinhos, ratos, coelhos, cães, gatos, bovinos, cavalos, porcos, cabras, ovelhas e macacos, de um modo mais preferido, de humanos.

Além disso, numa forma de realização preferida, os polinucleótidos arbitrários utilizados na presente invenção incluem polinucleótidos que regulam a expressão de uma proteína essencial para o desenvolvimento fetal. Tais polinucleótidos incluem, por exemplo: (a) ADN que expressam ARN complementares ao produto de transcrição de um ADN que codifica uma proteína essencial para o desenvolvimento fetal; (b) ADN que expressam ARN tendo uma atividade ribozima para dissociar especificamente o produto de transcrição de um ADN que codifica uma proteína essencial para o desenvolvimento fetal; (c) ADN que expressam ARN tendo uma atividade iARN para dissociar especificamente o produto de transcrição de um ADN que codifica uma proteína essencial para o desenvolvimento fetal; e (d) ADN que se ligam especificamente a um fator regulador da transcrição de um ADN que codifica uma proteína essencial para o desenvolvimento fetal e que regula a sua expressão.

Aqui, "regulação da expressão de uma proteína essencial para o desenvolvimento fetal" inclui a melhoria ou a supressão da transcrição de um gene que codifica uma proteína essencial para o desenvolvimento fetal, ou a melhoria ou a supressão da sua tradução numa proteína.

Numa forma de realização, "polinucleótido que regula a expressão de uma proteína essencial para o desenvolvimento fetal" é um ADN que codifica um ARN antimensageiro complementar ao produto de transcrição de um ADN que codifica uma proteína essencial para o desenvolvimento fetal. 0 efeito antimensageiro foi demonstrado pela primeira vez utilizando o método de expressão de genes transitório, com base na observação de que os ARN antimensageiros exercem um efeito antimensageiro quando introduzidos em plantas por eletroporação (Ecker e Davis, Proc. Natl. Acad. USA, 83: 5372, 1986) . Após esta observação, foram relatados outros casos, onde os níveis de expressão dos genes alvo foram reduzidos por expressão de ARN antimensageiro em tabaco ou petúnia (Krol et al., Nature 333: 866, 1988) . Até à data, o efeito antimensageiro foi estabelecido como um método para suprimir a expressão de genes em eucariotas, incluindo animais e plantas. A ação de ácidos nucleicos antimensageiros na supressão da expressão de genes alvo inclui: inibição da iniciação da transcrição por formação de tríplices; supressão da transcrição por formação de híbridos com um sítio tendo uma estrutura em ansa aberta local gerada por ARN-polimerase; inibição da transcrição por formação de híbridos com ARN à medida que a sua síntese avança; supressão da excisão-ligação por formação de híbridos numa junção intrão-exão; supressão da excisão-ligação por formação de híbridos com o sítio de formação de spliceossoma; supressão do transporte do núcleo para o citoplasma por formação de híbridos com ARNm; supressão da excisão-ligação por formação de híbridos com o sítio de terminação ou sítio de adição de poli(A); supressão da iniciação da tradução por formação de híbridos com o sítio de ligação do fator de iniciação da tradução; supressão da tradução por formação de híbridos com o sítio de ligação de ribossoma adjacente ao codão de iniciação; prevenção do alongamento da cadeia peptídica por formação de híbridos com a região de tradução ou o sítio de ligação de polissomas do ARNm; e supressão da expressão de genes por formação de híbridos com o sítio de interação ácido nucleico-proteína. Estas inibem o processo de transcrição, excisão-ligação, ou tradução, e suprimem a expressão de genes alvo (Hirashima e Inoue, Shin Seikagaku Jikkenkoza 2 (New Lecture for Experimental Biochemistry 2) , Kakusan IV (Nucleic Acid IV), Replication and Expression of Genes; Ed., Japanese Biochemical Society, Tokyo Kagaku Dojin Co., Ltd., pp. 319-347, 1993). A expressão de uma proteína endógena essencial para ο desenvolvimento fetal pode ser também suprimida utilizando ADN que codificam ribozimas. A ribozima refere-se a uma molécula de ARN com atividade catalítica. Existem várias ribozimas com diferentes atividades e, em particular, os estudos de ribozimas que funcionam como enzimas de dissociação de ARN têm permitido a conceção de ribozimas para a dissociação de ARN específica para um lócus. As ribozimas incluem aquelas que compreendem 400 nucleótidos ou mais, tais como o ARN de tipo intrão do grupo I e Ml incluído no ARNseP, bem como ribozimas com um domínio ativo de cerca de 40 nucleótidos, denominadas ribozimas em cabeça de martelo ou em grampo (Makoto Koizumi e Eiko Otsuka, Tanpakushitu, Kakusan, Koso (Proteína, Ácido Nucleico e Enzima), 35:2191, 1990) .

Por exemplo, o domínio de autodissociação das ribozimas em cabeça de martelo dissocia G13U14C15 na extremidade 3' de C15. O emparelhamento de bases de U14 com A na posição 9 é importante para esta atividade e foi demonstrado que ocorria dissociação mesmo quando o nucleótido na posição 15 é A ou U, em vez de C (Koizumi et al.r FEBS Lett. 228:225, 1988). Quando o sitio de ligação de substrato de uma ribozima é concebido para ser complementar a uma sequência de ARN adjacente ao sitio alvo, é possivel gerar uma ribozima de dissociação de ARN semelhante a enzima de restrição que reconhece a sequência UC, UU ou UA no ARN alvo (Koizumi et al., FEBS Lett. 239:285, 1988; Makoto

Koizumi e Eiko Otsuka, Tanpakushitu, Kakusan, Koso (Proteina, Ácido Nucleico e Enzima), 35:2191, 1990; Koizumi et al., Nucleic Acids Res. 17:7059, 1989).

As ribozimas em grampo são também úteis para a finalidade da presente invenção. Por exemplo, as ribozimas em grampo são encontradas na cadeia menos de ARN satélite no virus dos anéis de tabaco (Buzayan, Nature 323:349, 1986). Foi demonstrado que esta ribozima pode ser também concebida para dissociar ARN de um modo especifico para o alvo (Kikuchi e Sasaki, Nucleic Acids Res. 19:6751, 1992; Yo Kikuchi, Kagaku To Seibutsu (Quimica e Biologia) 30:112, 1992).

Numa forma de realização alternativa, "polinucleótido que regula a expressão de uma proteina essencial para o desenvolvimento fetal" é um ADN que codifica um ARN de cadeia dupla (ARNds) complementar ao produto de transcrição de um ADN endógeno que codifica uma proteina essencial para o desenvolvimento fetal. A introdução de um ARNds compreendendo uma sequência idêntica ou semelhante a uma sequência do gene alvo nas células pode originar o fenómeno chamado interferência de ARN (iARN), onde as expressões do gene estranho introduzido e do gene endógeno alvo estão suprimidas. Quando cerca de 40 a algumas centenas de pares de bases de ARNds são introduzidas nas células, uma nuclease semelhante a RNase III denominado Dicer, que tem um domínio helicase, processa os ARNds a partir das suas extremidades 3' em cerca de 21 a 23 pares de bases de ARN de interferência curtos (ARNsi) na presença de ATP. Proteínas específicas ligam-se aos ARNsi para formar complexos de nuclease (complexos de silenciamento induzidos por ARN (RISC)). Os complexos reconhecem e ligam-se à mesma sequência que o ARNsi e dissociam, em seguida, o produto de transcrição (ARNm) de um gene alvo na posição correspondente ao centro do ARNsi pela atividade enzimática semelhante a RNaselII. Noutra via, a cadeia antissentido de ARNsi liga-se ao ARNm e serve como um iniciador para a polimerase de ARN dependente de ARN (RsRP) para sintetizar ARNds. É também considerada outra via onde este ARNds também serve como um substrato para a Dicer, produzindo novos ARNsi para amplificar o efeito. A iARN foi originalmente encontrada em Caenorhabd.it is elegans (Fire, A. et al. Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature 391, 806-811, 1998) e até agora foi observada não só na

Caenorhabditis elegans mas também em vários organismos, tais como plantas, Nematoda, Drosophila e Protozoa (Fire, A. RNA-triggered gene silencing. Trends Genet. 15, 358-363 (1999); Sharp, P. A. RNA interference 2001. Genes Dev. 15, 485-490 (2001); Hammond, S. M., Caudy, A. A. & Hannon, G. J.

Post-transcriptional gene silencing by double-stranded RNA. Nature Rev. Genet. 2, 110-119 (2001); Zamore, P. D. RNA interference: listening to the sound of silence. Nat Struct

Biol. 8, 746-750 (2001)) . Foi confirmado que a expressão do gene alvo era suprimida quando ARNds exógenos são introduzidos nestes organismos. A iARN está também a ser utilizada como um método para produzir animais com gene inativado.

Na altura em que a iARN foi descrita, pensa-se que apenas um comprimento particular (40 nucleótidos) ou mais comprido de ARNds fosse eficaz. No entanto, Tuschl et al. na Rockefeller University nos EUA relataram que a introdução de cerca de 21 pares de bases de ARNds de cadeia única (ARNsi) nas células produzia um efeito de iARN sem induzir resposta antiviral mediada por PKR, nem mesmo em células de mamíferos (Tuschl, Nature, 411, 494-498 (2001)). Desde então, a iARN tem atraído muito mais atenção como uma tecnologia aplicável a células de mamíferos diferenciadas, tal como células humanas.

Um ADN para utilização nos métodos da presente invenção compreende um ADN codificante antimensageiro que codifica um ARN antimensageiro para qualquer região dentro do produto de transcrição (ARNm) de um gene alvo e um ADN codificante

mensageiro que codifica um ARN mensageiro para qualquer região dentro do mesmo ARNm, e permite a expressão do ARN antimensageiro e do ARN mensageiro a partir do ADN codificante antimensageiro e do ADN codificante mensageiro, respetivamente. Além disso, um ARNds pode ser também preparado a partir dos ARN antimensageiro e mensageiro. Na presente invenção, a sequência alvo não está particularmente limitada, desde que um ARNds compreendendo uma sequência idêntica ou semelhante à sequência alvo suprima a expressão de um ADN que codifica uma proteína essencial para o desenvolvimento fetal quando introduzida nas células.

Quando um sistema de expressão para o ARNds para utilização nos métodos da presente invenção é mantido num vetor ou semelhante, a construção pode fazer com que os ARN antimensageiro e mensageiro sejam expressos a partir de um único vetor ou independentemente de diferentes vetores. Por exemplo, guando os ARN antimensageiro e mensageiro são expressos a partir de um único vetor, pode preparar-se uma construção construindo separadamente uma cassete de expressão para o ARN antimensageiro e uma cassete de expressão para o ARN mensageiro, onde um promotor, tal como a série polIII, gue permite a expressão de um ARN curto, é ligada a montante do ADN codificante antimensageiro e ADN codificante mensageiro, respetivamente, e inserindo, em seguida, estas cassetes num vetor na mesma ou em orientação inversa.

Alternativamente, o sistema de expressão pode ser construído, de tal modo que o ADN codificante antimensageiro e o ADN codificante mensageiro são organizados em cadeias separadas e na direção oposta. Esta construção compreende um ADN de cadeia dupla (ADN codificante de ARNsi) em que a cadeia codificante do ARN antimensageiro e a cadeia codificante do ARN mensageiro são emparelhadas entre si e os promotores são organizados em ambas as suas extremidades na direção oposta, de tal modo que o ARN antimensageiro ou ARN mensageiro pode ser expresso a partir de cada cadeia. Neste caso, prefere-se que uma sequência de terminação esteja organizada na extremidade 3' de cada cadeia (cadeia codificante do ARN antimensageiro ou cadeia codificante do ARN mensageiro) para impedir a adição de sequências adicionais a jusante do ARN mensageiro e ARN antimensageiro. Uma sequência de quatro ou mais nucleótidos de adenina (A) consecutivos ou semelhantes pode ser utilizada como a sequência de terminação. Além disso, os dois promotores são, de um modo preferido, diferentes neste sistema de expressão palindrómico.

Entretanto, quando o ARN antimensageiro e o ARN mensageiro são expressos a partir de vetores separados, podem ser preparadas construções, por exemplo, construindo separadamente uma cassete de expressão para o ARN antimensageiro e uma cassete de expressão para o ARN mensageiro, onde é ligado um promotor, tal como a série polIII, que permite a expressão de um ARN curto, a montante do ADN codificante antimensageiro e ADN codificante mensageiro, respetivamente, e inserindo, em seguida, estas cassetes em vetores separados.

Um ARNsi pode ser utilizado como o ARNds para a iARN. "ARNsi" refere-se a um ARN de cadeia dupla constituído por cadeias curtas dentro de uma gama não citotóxica, e não está limitado a ARNsi com um comprimento total de 21 a 23 pares de bases como descritos por Tuschl et al. (supra). 0 ARNsi não está particularmente limitado, desde que o seu comprimento esteja dentro de uma gama não tóxica; por exemplo, o comprimento pode situar-se na gama de 15 a 49 pares de bases, de um modo preferido, 15 a 35 pares de bases e, de um modo mais preferido, 21 a 30 pares de bases. Alternativamente, o comprimento final da porção de ARN de cadeia dupla formada do ARNsi expresso como consequência de transcrição pode situar-se, por exemplo, na gama de 15 a 49 pares de bases, de um modo preferido, 15 a 35 pares de bases e, de um modo mais preferido, 21 a 30 pares de bases.

Como ADN para serem utilizados nos métodos da presente invenção, podem ser utilizadas construções que formam um ARN de cadeia dupla com uma estrutura em grampo (ARN "em grampo" autocomplementar (ARNhp)) preparadas inserindo uma sequência apropriada (de um modo preferido, uma sequência intrónica) entre as repetições invertidas de uma sequência alvo (Smith, N.A., et al. Nature, 407: 319, 2000; Wesley, S. V et al. Plant J. 27: 581, 2001; Piccin, A. et al. Nucleic Acids Res. 29:E55, 2001). Não é necessário que os ADN utilizados para a iARN sejam perfeitamente idênticos ao gene alvo; contudo, têm pelo menos 70% ou mais, de um modo preferido 80% ou mais, e de um modo mais preferido 90% ou mais (por exemplo, 95%, 96%, 97%, 98%, 99% ou mais) de identidade de sequência. A identidade de sequência pode ser determinada pelos métodos descritos acima.

Os especialistas na técnica podem preparar os ADN anteriores utilizando técnicas de engenharia genética comuns. Os ADN podem ser preparados, por exemplo, sintetizando sequências arbitrárias utilizando métodos de síntese de oligonucleótidos bem conhecidos.

Os ADN podem ser introduzidos nos cromossomas celulares e expressos nas células tal como se encontram; contudo, os ADN anteriores são, de um modo preferido, transportados por vetores para a transferência eficiente de genes nas células, e semelhantes. São também aqui descritos vetores que compreendem ADN para utilização nos métodos da presente invenção.

Além disso, noutra forma de realização, "polinucleótido que regula a expressão de um polinucleótido que codifica uma proteína essencial para o desenvolvimento fetal" inclui ADN que regulam a expressão ligando-se especificamente a um fator regulador da transcrição para o ADN que codifica uma proteína essencial para o desenvolvimento fetal. Como um exemplo de tais ADN, são conhecidos os ADN engodo. Os ADN engodo incluem, por exemplo, cerca de 2 0 nucleótidos de ADN que compreendem uma sequência complementar a um fator regulador da transcrição tal como NF-kB. Os ADN engodo inibem a função de um fator regulador da transcrição ligando-se ao fator. Como consequência, a expressão de uma proteina que é regulada pelo fator regulador da transcrição é também suprimida.

Assim, os polinucleótidos que são introduzidos especificamente na trofectoderme pelos métodos da presente invenção incluem, não só polinucleótidos que codificam uma proteina essencial para o desenvolvimento fetal mas também polinucleótidos que regulam a expressão de uma proteina essencial para o desenvolvimento fetal. Por exemplo, a função de um gene na embriogénese pode ser analisada introduzindo nos blastocistos um polinucleótido que regula a expressão de uma proteina essencial para o desenvolvimento fetal. É possivel determinar se um polinucleótido arbitrário foi introduzido especificamente na trofectoderme de um blastocisto não humano pelos métodos da presente invenção, utilizando métodos conhecidos dos especialistas na técnica, por exemplo, amplificando genes introduzidos por PCR, ou detetando a expressão de um gene repórter, tais como EGFP ou lacZ, com um método de fluorescência ou luminescência, ou semelhante.

Os blastocistos não humanos a serem introduzidos com os polinucleótidos anteriores que codificam uma proteina essencial para o desenvolvimento fetal ou polinucleótidos que regulam a expressão de uma proteina essencial para o desenvolvimento fetal não estão particularmente limitados. Os blastocistos não humanos a serem introduzidos com tais polinucleótidos incluem, por exemplo, blastocistos derivados de animais tendo uma anormalidade numa proteína essencial para o desenvolvimento fetal ou na sua regulação da expressão de proteínas. Aqui, "proteína essencial para o desenvolvimento fetal" refere-se a uma proteína envolvida direta ou indiretamente no desenvolvimento fetal, como descrito acima. Especificamente, as proteínas incluem aquelas que compreendem as sequências de aminoácidos codificadas pelas sequências de nucleótidos das SEQ ID Ns: 1 a 16 e 19 a 51, e proteínas compreendendo a sequência de aminoácidos das SEQ ID N2: 17 ou 18. Além disso, " tendo uma anormalidade numa proteína essencial para o desenvolvimento fetal" refere uma condição em que a proteína essencial para o desenvolvimento fetal é estruturalmente ou funcionalmente anormal. Alternativamente, " tendo uma anormalidade na regulação da expressão de uma proteína essencial para o desenvolvimento fetal" refere-se a ter uma anormalidade em qualquer um ou em ambos os seguintes processos: a transcrição de um ADN que codifica uma proteína essencial para o desenvolvimento fetal em ARN e a tradução do referido ARN em proteína. Além disso, na presente invenção, " tendo uma anormalidade na regulação da expressão de uma proteína" inclui, não só o caso de a produção da proteína ser completamente inibida devido a uma anormalidade em qualquer um ou em ambos os processos de transcrição e tradução, mas também o caso em que o nível ou momento de expressão das proteínas não é normal ou em que a proteína é produzida com uma anormalidade na parte da função ou estrutura da proteína normal.

Por exemplo, os animais não humanos que não pudessem nascer naturalmente devido a letalidade embrionária podem nascer introduzindo um polinucleótido que codifica uma proteína essencial para o desenvolvimento fetal nos blastocistos dos animais que têm uma anormalidade na proteína que é essencial para o desenvolvimento fetal ou na sua regulação da expressão de proteínas.

Os animais não humanos dos quais são provenientes os blastocistos incluem, mas não estão particularmente limitados a, ratinhos, ratos, coelhos, cães, gatos, bovinos, cavalos, porcos, cabras, ovelhas, macacos, e semelhantes.

Como descrito acima, os "polinucleótidos que regulam a expressão de uma proteína essencial para o desenvolvimento fetal" podem ser também introduzidos nos blastocistos. Formas de realização específicas de tais polinucleótidos são descritas acima. Além disso, os blastocistos não humanos nos quais são introduzidos esses polinucleótidos incluem blastocistos de animais tendo uma anormalidade numa proteína essencial para o desenvolvimento fetal ou na sua regulação da expressão de proteínas, e blastocistos que não têm uma anormalidade em proteínas essenciais para o desenvolvimento fetal ou na sua regulação da expressão de proteínas. Quando um polinucleótido que regula a expressão de uma proteína essencial para o desenvolvimento fetal é um polinucleótido que aumenta a expressão de uma proteína essencial para o desenvolvimento fetal, por exemplo, animais que não podiam nascer naturalmente devido a letalidade embrionária, podem nascer introduzindo o polinucleótido nos blastocistos de animais tendo uma anormalidade numa proteína essencial para o desenvolvimento fetal ou na sua regulação da expressão de proteínas.

Alternativamente, quando um polinucleótido que regula a expressão de uma proteína essencial para o desenvolvimento fetal, é um polinucleótido que suprime a expressão de uma proteína essencial para o desenvolvimento fetal, por exemplo, podem identificar-se genes essenciais para o desenvolvimento fetal, ou a função de genes no desenvolvimento fetal pode ser analisada introduzindo o polinucleótido em blastocistos que não têm uma anormalidade em proteínas essenciais para o desenvolvimento fetal ou na sua regulação da expressão de proteínas.

Assim, os especialistas na técnica podem utilizar os métodos da presente invenção para vários fins e aplicações selecionando polinucleótidos apropriados a serem introduzidos e blastocistos não humanos apropriados, nos quais são introduzidos os polinucleótidos. Nos métodos da presente invenção, os polinucleótidos a serem introduzidos não estão particularmente limitados. Além disso, as combinações de polinucleótidos a serem introduzidos não estão limitadas. A presente invenção refere-se também a métodos de produção de blastocistos não humanos onde é introduzido especificamente um polinucleótido arbitrário nas células trofectodérmicas.

Nos métodos da presente invenção, para produzir blastocistos não humanos, em primeiro lugar, a zona pelúcida é removida dos blastocistos. Pode utilizar-se quaisquer blastocistos não humanos. Os blastocistos podem ser também obtidos, por exemplo, pelos métodos descritos acima. Além disso, a zona pelúcida pode ser removida, por exemplo, pelos métodos descritos acima, mas os métodos não estão limitados àqueles.

Nos métodos da presente invenção para produzir blastocistos não humanos, os polinucleótidos arbitrários são em seguida introduzidos nos blastocistos anteriores. Os polinucleótidos podem ser introduzidos pelos métodos descritos acima, mas os métodos não estão limitados àqueles.

Nos métodos da presente invenção para produzir blastocistos não humanos, não há limitação quanto ao tipo de polinucleótido a ser introduzido e podem ser introduzidos quaisquer polinucleótidos. Numa forma de realização preferida, tais polinucleótidos incluem polinucleótidos que codificam uma proteína essencial para o desenvolvimento fetal ou polinucleótidos que regulam a expressão de uma proteína essencial para o desenvolvimento fetal. As formas de realização específicas destes polinucleótidos são também como descritas acima.

Além disso, não há limitação quanto ao tipo de blastocisto não humano no qual os polinucleótidos descritos acima são introduzidos. Por exemplo, pode utilizar-se os blastocistos não humanos descritos acima.

Nos métodos da presente invenção para produzir blastocistos não humanos, não existe limitação quanto ao polinucleótido a ser introduzido, ao blastocisto não humano no qual o polinucleótido é introduzido ou às suas combinações. Os especialistas na técnica podem produzir e utilizar combinações apropriadas dependendo da finalidade. São aqui descritos métodos de produção de animais não humanos e métodos para resgatar animais não humanos da letalidade embrionária.

Nos métodos de produção de animais não humanos descritos, em primeiro lugar, a zona pelúcida é removida dos blastocistos de um animal não humano. Pode utilizar-se quaisquer blastocistos não humanos para este efeito. Os blastocistos a serem utilizados nos métodos de produção de animais não humanos descritos são, de um modo preferido, mas não estão limitados a, blastocistos de animais não humanos tendo uma anormalidade numa proteína essencial para o desenvolvimento fetal ou na sua regulação da expressão de proteínas. Os polinucleótidos podem ser introduzidos em tais blastocistos para gerar animais não humanos resgatados da letalidade embrionária devido a anormalidade placentária.

Tais blastocistos podem ser obtidos pelos métodos descritos acima. A zona pelúcida pode ser também removida por quaisquer métodos, por exemplo, os métodos descritos acima.

Nos métodos de produção de animais não humanos descritos, um polinucleótido arbitrário é, em seguida, introduzido nos blastocistos anteriores. 0 polinucleótido pode ser também introduzido pelos métodos descritos acima.

Nos métodos de produção de animais não humanos descritos, não há limitação quanto ao tipo de polinucleótido a ser introduzido. Numa forma de realização preferida, o polinucleótido inclui polinucleótidos que codificam uma proteína essencial para o desenvolvimento fetal ou polinucleótidos que normalizam a regulação da expressão de uma proteína essencial para o desenvolvimento fetal. As formas de realização específicas do polinucleótido que codifica uma proteína essencial para o desenvolvimento fetal são como descritas acima.

Além disso, os polinucleótidos que normalizam a regulação da expressão de uma proteína essencial para o desenvolvimento fetal incluem polinucleótidos que podem corrigir anormalidades em qualquer um ou em ambos os seguintes processos: transcrição de um ADN que codifica uma proteína essencial para o desenvolvimento fetal em ARN e tradução do ARN em proteína. Aqui, normalização significa não só correção perfeita da anormalidade, mas também correção parcial da anormalidade e redução do grau de anormalidade.

Nos métodos de produção de animais não humanos descritos, os blastocistos não humanos anteriores são finalmente transplantados num recetor. 0 recetor é, de um modo preferido, o mesmo animal ou um animal que pertence à mesma espécie animal que o animal de onde os blastocistos são derivados. Os especialistas na técnica podem transplantar rotineiramente blastocistos nos recetores (Manipulating the mouse embryo, a laboratory manual, 3a edição, p263-271, Cold Spring Harbor Laboratory Press) . Os animais não humanos a serem produzidos incluem, mas não estão limitados a, por exemplo, ratinhos, ratos, coelhos, cães, gatos, bovinos, cavalos, porcos, cabras, ovelhas, macacos, e semelhantes.

Assim, animais não humanos com letalidade embrionária podem ser produzidos utilizando os métodos de introdução de polinucleótidos especificamente nas células trofectodérmicas. Deve referir-se que os animais não humanos produzidos pelos métodos aqui descritos não são animais quiméricos porque não têm nos seus corpos o polinucleótido introduzido nos blastocistos. São aqui adicionalmente descritos métodos para resgatar animais não humanos da letalidade embrionária. Nos métodos descritos para resgatar animais não humanos da letalidade embrionária, em primeiro lugar, a zona pelúcida é removida dos blastocistos de um animal não humano tendo uma anormalidade numa proteína essencial para o desenvolvimento fetal ou na sua regulação da expressão de proteínas. As formas de realização de animais não humanos tendo uma anormalidade numa proteína essencial para o desenvolvimento fetal e animais não humanos tendo uma anormalidade na regulação da expressão da proteína essencial para o desenvolvimento fetal são como descritos acima. Tais blastocistos podem ser obtidos, por exemplo, pelos métodos descritos acima. A zona pelúcida pode ser também removida por quaisquer métodos e os métodos descritos acima.

Nos métodos descritos para resgatar animais não humanos da letalidade embrionária, polinucleótidos que codificam uma proteína essencial para o desenvolvimento fetal ou polinucleótidos que normalizam a regulação da expressão de uma proteína essencial para o desenvolvimento fetal são, em seguida, introduzidos nos blastocistos anteriores. Os polinucleótidos podem ser também introduzidos pelos métodos descritos acima.

Nos métodos descritos para resgatar animais não humanos da letalidade embrionária, os blastocistos anteriores são transplantados num recetor para dar à luz animais recém-nascidos. 0 recetor é, de um modo preferido, o mesmo animal ou um animal que pertence à mesma espécie animal que o animal do qual os blastocistos são derivados. Os especialistas na técnica podem transplantar blastocistos nos recetores e dar à luz animais recém-nascidos utilizando métodos convencionais.

Além disso, os animais não humanos a serem resgatados incluem, mas não estão limitados a, por exemplo, ratinhos, ratos, coelhos, cães, gatos, bovinos, cavalos, porcos, cabras, ovelhas, macacos, e semelhantes.

Além disso, são aqui descritos métodos de triagem de polinucleótidos que resgatem da letalidade embrionária, os quais compreendem os seguintes passos: (a) remover a zona pelúcida dos blastocistos de um animal não humano tendo uma anormalidade numa proteína essencial para o desenvolvimento fetal ou na sua regulação da expressão de proteínas; (b) introduzir polinucleótidos arbitrários nos blastocistos obtidos no passo (a); (c) transplantar os blastocistos obtidos no passo (b) num recetor não humano para dar à luz um animal recém-nascido; e (d) selecionar polinucleótidos que resgataram da letalidade embrionária em comparação com quando não foi introduzido o polinucleótido arbitrário.

Nos métodos de triagem descritos, em primeiro lugar, a zona pelúcida é removida dos blastocistos de um animal não humano tendo uma anormalidade numa proteína essencial para o desenvolvimento fetal ou na sua regulação da expressão de proteínas. As formas de realização específicas de animais não humanos tendo uma anormalidade numa proteína essencial para o desenvolvimento fetal ou na sua regulação da expressão de proteínas são como descritas acima. A remoção de blastocistos pode ser conseguida pelos métodos descritos acima, mas não está limitada àqueles.

Nos métodos de triagem descritos, em seguida são introduzidos polinucleótidos arbitrários nos blastocistos obtidos como descrito acima. Pode introduzir-se quaisquer polinucleótidos, e o seu comprimento e origem, e os métodos para obtê-los não estão limitados. Os polinucleótidos utilizados nos métodos de triagem podem ser quimicamente sintetizados, ou derivados de fontes naturais, por exemplo, bibliotecas de genes tal como bibliotecas de ADNc, e produtos de transcrição das bibliotecas de genes. Além disso, estes polinucleótidos podem ser utilizados após marcação apropriada, consoante necessário. Tal marcação inclui, por exemplo, marcação radioativa, marcação fluorescente, e semelhantes. Estes polinucleótidos podem ser introduzidos nos blastocistos pelos métodos descritos acima.

Nos métodos de triagem descritos, os blastocistos não humanos anteriores introduzidos com um polinucleótido arbitrário são em seguida transplantados num recetor não humano para dar à luz animais recém-nascidos. Como descrito acima, os blastocistos podem ser transplantados em recetores não humanos e os animais recém-nascidos podem ser obtidos por métodos convencionais utilizados pelos especialistas na técnica.

Nos métodos de triagem descritos, os polinucleótidos que resgataram da letalidade embrionária são selecionados em comparação com quando não é introduzido o polinucleótido arbitrário. Os polinucleótidos selecionados podem servir como polinucleótidos que normalizam a regulação da expressão de uma proteina essencial para o desenvolvimento fetal e, são assim, úteis na produção ou resgate de animais não humanos, que morreriam naturalmente devido a letalidade embrionária.

Alternativamente, estes polinucleótidos podem ser utilizados como agentes terapêuticos para doenças provocadas por uma anormalidade em proteínas essenciais para o desenvolvimento fetal ou na sua regulação da expressão.

Exemplos A seguir, a presente invenção será descrita mais especificamente com respeito aos Exemplos, mas não está limitada aos mesmos.

Materiais e métodos (1) Método baseado em LV de produção de TG (Método convencional)

Foi administrada PMSG (gonadotrofina sérica de égua grávida) a ratinhos BDF1 fêmeas e, após cerca de 48 horas, foi administrada HCG para induzir superovulação. Os ratinhos foram acasalados com ratinhos BDF1 machos. Cerca de 48 horas após o acasalamento, embriões do passo de duas a quatro células foram lavados para fora dos ovidutos em meio FHM. A zona pelúcida foi removida por tratamento com solução de Tyrode ácida. Em seguida, os óvulos fertilizados foram colocados um por um numa região de solução viral (1 x 108 ng/mL) para infeção. Os óvulos foram cultivados até se transformarem em blastocistos. Depois de lavar com meio kSOM, os blastocistos foram transplantados no útero de um ratinho pseudográvido (no dia 2,5 da pseudogravidez). (2) Resgate tetraploide (Método convencional)

Tetraploide refere-se a um embrião tetraploide. 0 embrião contribui principalmente para a placenta que é um tecido extraembrionário. Quando uma quimera de agregação é preparada com um embrião tetraploide e um embrião de um ratinho mutante com anormalidade placentária, o ratinho mutante pode ser desenvolvido na placenta com funções normais.

Foi administrada PMSG a ratinhos BDF1 fêmeas e, após cerca de 48 horas, foi administrada HCG para induzir superovulação. Os ratinhos foram acasalados com ratinhos BDF1 machos. Cerca de 48 horas após o acasalamento, os embriões do passo de duas células foram lavados para fora dos ovidutos em meio FHM. Foram produzidas quimeras de agregação desenvolvendo embriões do passo de quatro células de uma célula tetraploide obtida fundindo eletricamente embriões do passo de duas células diploides em conjunto; e colocando-os em contacto próximo com embriões do passo de oito células obtidos por tratamento de superovulação no mesmo plano e por acasalamento de heterozigotos +/-, depois da zona pelúcida ter sido removida por tratamento com solução de Tyrode ácida. Os embriões foram cultivados em meio kSOM até se transformarem em blastocistos. Os blastocistos foram transplantados no útero de um ratinho pseudográvido (no dia 2,5 de pseudogravidez). (3) Método de transferência de genes específicos para a placenta que utiliza LV (Método da presente invenção)

Foi administrada PMSG a ratinhos +/- fêmeas e, após cerca de 48 horas, foi administrada HCG para induzir superovulação. Os ratinhos foram acasalados com ratinhos +/- machos. Cerca de 48 horas após acasalamento, os embriões do passo de duas a quatro células foram lavados para fora dos ovidutos em meio FHM. Os embriões do passo de duas a quatro células foram cultivados em meio kSOM durante cerca de 48 horas até se transformarem em blastocistos. Depois da zona pelúcida ter sido removida por tratamento com solução de Tyrode ácida, os blastocistos foram colocados um por um numa região de solução viral (1 x 103 ng/mL) para infeção. 0 tempo de infeção foi quatro a cinco horas. Os blastocistos recolhidos da solução virai foram lavados uma vez, e, em seguida, os blastocistos foram transplantados no útero de um ratinho pseudográvido (no dia 2,5 de pseudogravidez). (4) Secções de tecido

As placentas foram fixas com paraformaldeído a 4% a 4 °C durante 12 horas e, em seguida, lavadas em PBS a 4 °C durante duas ou três horas. 0 PBS foi substituído por acetona e após uma ou duas horas, a acetona foi substituída por 1,5 mL/tecido de solução de Technovit 8400 (0,06 g/10 mL). Os tecidos foram fixos durante cerca de duas horas. Depois dos tecidos terem

precipitado, foram adicionados 50 pL de solução de Technovit 8400 (frasco pequeno). Os tecidos e resina foram adicionados dentro da grelha, cobertos e, em seguida, incubados a 4 °C durante 12 horas para embutimento. Foram produzidas secções finas e observadas. (5) Transferência de Western

As caudas dos recém-nascidos foram homogeneizadas em tampão de lise utilizando um homogeneizador. Os lisados foram deixados sobre gelo com agitação ocasional durante 1 hora e, em seguida, centrifugados a 13000 rpm e 4 °C durante 20 minutos. Os sobrenadantes resultantes foram utilizados como extratos. As concentrações foram determinadas e ajustadas para serem constantes. Em seguida, os extratos foram carregados e submetidos a eletroforese. Após eletroforese, as amostras foram transferidas para uma membrana de PCDF (Immobilon-P, Millipore, Bedford, MA) . Após bloqueio com tampão de TBS-T que continha 5% de leite desnatado, a membrana foi feita reagir com um anticorpo primário (ERK2, BD pan ERK N2 610123; p38a, Santa Cruz p38 (C-20) N2 sc-535) , a 4 °C de um dia para o outro. A membrana foi lavada três vezes com tampão de TBS-T e em seguida incubada com um anticorpo anti-ratinho ou anticorpo anti-coelho marcado com HRP à temperatura ambiente durante uma hora. Depois de lavar quatro vezes com tampão de TBS-T, foi utilizado ECL™ (RPN2209) para desenvolvimento de cor e foi desenvolvida uma imagem.

(6) PCR

Os ADN genómicos foram extraídos de uma porção dos tecidos de fetos, placentas e recém-nascidos para examinar os seus genótipos pelo método de PCR. Os iniciadores e as condições de PCR utilizados são mostrados a seguir.

Tipagem de EGFP

Iniciador-1378: gagctagccaccatggtgagcaagggcgag (SEQ ID N2: 52)

Iniciador-1382: tcaccttgatgccgttcttct (SEQ ID N2: 53) Condições de PCR: 94 °C durante dois minutos, 30 ciclos de (94 °C durante 30 segundos, 65 °C durante 30 segundos e 72 °C durante 30 segundos), e 72 °C durante dois minutos, seguido de 4 °C

Tipagem de ERK2

Iniciador-1331: taactgggtcgagcacagtgatgc (SEQ ID N2: 54)

Iniciador-1332: tcagaattgatctggtcttcaagaccttg (SEQ ID N2: 55)

Iniciador-1333: atgtatgctatacgaagttattagggc (SEQ ID N2: 56)

Condições de PCR: 95 °C durante dois minutos, 40 ciclos de (95 °C durante 20 segundos e 64 °C, durante

40 segundos), e 72 °C durante um minuto, seguido de 4 °C

Tipagem de p38

Iniciador-1380: ccctcgtggatggttgccagcagc (SEQ ID N2: 57)

Iniciador-1343: cttactttgcactgaacacacacatcc (SEQ ID N2: 58)

Condições de PCR: 94 °C durante dois minutos; 40 ciclos de 94 °C durante 30 segundos, 65 °C durante 30 segundos e 72 °C durante um minuto); e 72 °C durante dois minutos, seguido de 4 °C

Os produtos de PCR resultantes foram tratados com a enzima de restrição EcoRV. A genotipagem foi com base nas diferenças de tamanho entre os tipos selvagem e mutante.

[Exemplo 1] Infeção e avaliação de LV-CAG-EGFP A introdução de um lentivirus (LV) que tem o gene de GFP (LV-CAG-EGFP, o qual foi construído pelo método descrito em Molecular Therapy 2003, 8; 666-673; foi construído um plasmídeo de vetor lentiviral SIN introduzido com um ADNc que codifica o EGFP sob o controlo de um promotor CAG e combinado com um plasmídeo de empacotamento, plasmídeo de expressão de Rev e plasmídeo de expressão de VSVG; a mistura foi introduzida em células 293T pelo método de fosfato de cálcio; as partículas virais libertadas para o sobrenadante da cultura foram recolhidas e concentradas por ultracentrifugação; para os plasmídeos, ver Fig. 1) foi tentada utilizando o método TG e o método da presente invenção. 0 gene utilizado nesta experiência foi o gene de GFP, e as áreas introduzidas com o gene emitem fluorescência verde. Os indivíduos introduzidos com o gene por cada método foram examinados quanto ao sítio de infeção e avaliados para a eficácia da infeção por observação microscópica, secções de tecido, PCR, e semelhantes.

Com o método TG, o feto E13.5 e a placenta emitiram fluorescência verde, e o gene foi introduzido em ambos (Fig. 2) . No entanto, com o método da presente invenção, o gene foi introduzido apenas na placenta e não no feto (Fig. 2) . Uma comparação das secções de placenta não tratada e placenta introduzida com o gene pelo método da presente invenção demonstrou que o gene foi introduzido em toda a área da placenta que tinha a introdução do gene pelo método da presente invenção (Fig. 3) . Além disso, a introdução do gene foi examinada por PCR. Com o método TG, o gene foi introduzido apenas na placenta nalguns casos; contudo, em cerca de 60% de todos os casos (38 dos 66 indivíduos) , o gene foi introduzido na placenta e no feto (Tabela 1) . Pelo contrário, quando o mesmo vetor virai foi introduzido pelo método da presente invenção, o gene foi introduzido apenas na placenta em todos os 69 indivíduos e não em nenhum feto (Tabela 1) . Além disso, 91 recém-nascidos foram analisados, e o resultado mostrou que todos nasceram normalmente e que o gene não foi introduzido (Tabela 1) . As observações descritas acima demonstram que pode conseguir-se transferência de genes específicos para a placenta pelo método da presente invenção.

Tabela 1

(continuação)

[Exemplo 2] Resgate de ratinhos com o gene ERK2 e p38a inativado A seguir, as presentes requerentes especularam que a introdução de um gene de interesse pelos métodos da presente invenção em ratinhos mutantes que eram originalmente letais embrionários devido a anormalidade placentária poderia permitir o seu desenvolvimento e análise pós-natal. Ratinhos com gene erk2 inativado e ratinhos com o gene p38a inativado foram utilizados para estas experiências. (1) Ratinhos com gene erk2 inativado (Fig. 4)

Ratinhos com o gene erk2 inativado foram descritos como sendo letais embrionários cerca de E10.5 devido a anormalidade placentária (Hatano N. et al., Genes Cells. 2003 Nov; 8(11): 847-56). De acordo com Hatano N. et al., as camadas labirínticas são finas na placenta inativada; a parede do coração do feto torna-se mais fina e o seu desenvolvimento é retardado; e assim os embriões após E 11.5 são indetetáveis. O adelgaçamento das camadas labirínticas e a anormalidade da parede do coração foram melhorados pelo resgate tetraploide. Por conseguinte, Hatano N. et al., argumentaram que o adelgaçamento da parede do coração foi uma anormalidade secundária como consequência do fornecimento insuficiente de oxigénio e nutrientes a partir da placenta.

Foi construído um vetor lentiviral para expressar o ADNc de ERK2 sob o controlo de um promotor CAG (Fig. 3b). Depois da zona pelúcida ter sido removida dos blastocistos obtidos por acasalamento ERK2 +/- com ERK2+/-, os blastocistos foram infetados com o vetor virai e transplantados no útero de um ratinho pseudográvido. A genotipagem dos descendentes resultantes por PCR mostrou 16 ratinhos homozigóticos (Fig. 4c e 4d) . Os recém-nascidos homozigóticos pareciam ser ligeiramente pequenos mas saudáveis, e foram também observados a beber leite (Fig. 4e). Além disso, a transferência de Western demonstrou que a proteína ERK2 estava ausente nos ratinhos (Fig. 4f). (2) Ratinhos com o gene ρ38α inativado (Fig. 5)

Ratinhos com o gene p38a inativado foram descritos como sendo letais embrionários cerca de E10.5 devido a anormalidade placentária (Adams RH et al., Mol Cell. 2000 jul; 6(1): 109-16; Mudgett JS et al., Proc Natl Acad Sei USA., 12 de set de 2000; 97(19): 10454-9). Em ratinhos com o gene p38a inativado, as camadas labirínticas placentárias e a parede do coração fetal são finas e imperfeitas, e é observado angiogénese cerebral aberrante. Quando se formou placenta normal por resgate tetraploide nos ratinhos, a parede do seu coração e a angiogénese cerebral foram normais. Adams RH et al., descreveram que as anormalidades não placentárias foram assumidas como sendo devido ao fornecimento insuficiente de oxigénio e nutrientes a partir da placenta e, desse modo, a causa direta da letalidade embrionária é a anormalidade placentária.

Em ratinhos com o gene ρ38α inativado, o gene foi também introduzido especificamente nas suas placentas, utilizando um vetor lentiviral (Fig. 5b) e os seus genótipos foram determinados por PCR. Como consequência, nasceram 34 ratinhos homozigóticos (Fig. 5c e 5d). Os recém-nascidos de supressão homozigóticos pareciam ser ligeiramente pequenos mas saudáveis e foram também observados a beber leite (Fig. 5e) . Além disso, a transferência de Western demonstrou que a proteína p38a estava ausente nos ratinhos (Fig. 5f) .

Como descrito acima, foi estabelecido um sistema para transferência de genes específicos para a placenta, e foi demonstrado que ratinhos com genes inativados que são letais embrionários devido a anormalidade placentária podem nascer utilizando este sistema. Além disso, a utilização de ratinhos com genes inativados também permite análises funcionais pós-natais.

Quarenta ou mais tipos de ratinhos geneticamente mutantes que exibem anormalidade placentária já foram descritos em 2001 (Rossant J, Cross JC., Nat Rev Genet. 2001 jul; 2(7) :538-48. Revisão) . Quando os ratinhos são embrionários letais devido a anormalidade placentária, o gene não pode ser analisado quanto à sua função, ou semelhantes, após parto. Os métodos da presente invenção podem ser aplicados em experiências de resgate de tais ratinhos mutantes e permitem, desse modo, análises funcionais de genes pós-natais.

Embora o resgate tetraploide compense apenas a placenta anormal de um embrião e normalize a sua função, a utilização de LV permite que genes mutantes sejam expressos de um modo especifico para a placenta, e o LV pode ser também utilizado em combinação com iARN. Por exemplo, prevê-se que a função especifica para a placenta da ERK2 possa ser analisada quando um gene de ERK2 mutante funcione como um mutante negativo dominante na placenta.

Alternativamente, é também esperado que utilizando o LV, se possa analisar em pormenor não só cada gene, mas que possa ser também examinada a relação do gene com outros membros da subfamilia de genes e com genes a montante ou a jusante da via de sinalização. Assim, prevê-se que com estudos adicionais, o desenvolvimento do método de transferência de genes específicos para a placenta baseado em LV possa conduzir a investigação aplicada, tais como terapia genética e análise da função de genes ao nível individual.

Aplicabilidade Industrial A presente invenção proporciona métodos de introdução de genes especificamente em placenta não humana inteira. Os métodos de transferência de genes da presente invenção impõem apenas um pequeno esforço nas mães e fetos não humanos, porque não introduzem genes diretamente na placenta. Além disso, ao contrário do sistema de microinjeção, os presentes métodos não requerem dispositivos dispendiosos nem técnicas engenhosas.

Além disso, os métodos da presente invenção podem ser utilizados para introduzir vários genes na placenta não humana; isto não só complementa a função placentária em animais mutantes, mas também permite análises funcionais destes genes na placenta. Assim, os métodos da presente invenção são também úteis para estudos que analisam as funções de genes na embriogénese.

LISTAGEM DE SEQUÊNCIAS

<110> OKABE, MASARU IKAWA, MASAHITO FUSO PHARMACEUTICAL INDUSTRIES, LTD. <120> Sistema de manipulação de genes específicos para células trofoblásticas

<130> F2-A0502P <150> JP 2005-234258 <151> 2005-08-12 <160> 58 <170> Patentln versão 3.3 <210> 1 <211> 2631

<212> ADN <213> Mus musculus <400> 1 cgacaagagg taatccggga cgcggagaga ggcacgcagc gactgaccga cagccggcga 60 tggtctaagc gcccctcggc caccccctcc cccagacgcg accgcgtcct gccctcgccc 120 tctggacaca cacccccacc tgggctcctc cgcccgttcg gcgctcctcg gaggaggccc 180 ggggtgttgc ggcgctcgcc agcatgagcg gctccttcga tcgcaagctc agcagcatcc 240 tcaccgacat ctccagctcg ctcagctgcc atgcgggctc caaggactcg cccaccctgc 300 ccgaatctac agtcactgac ctgggctatt acagcgctcc tcagcatgac tactactcgg 360 gccagcccta cggccagacg gtgaacccct acacctacca ccaccagttc aatctcaatg 420 ggctcgcagg caccggcgct tactcgccca agtcggaata tacctacggg ggatcctata 480 ggcagtacgg agcgtaccgg gagcagcctt tgcctgccca ggacccagtg tcggtgaaag 540 aggagccgga agccgaggtt cgcatggtga acggcaagcc caaaaaggtc cgaaagccgc 600 gaacgatcta ctccagctat cagctggctg ccctgcagcg ccgtttccag aaagcccagt 660 atctggcctt gcctgagcgc gccgagctag ctgcacagct gggcctcaca caaacacagg 720 tgaaaatctg gttccagaac cgccgctcca agttcaaaaa gctctataag aatggggagg 780 tgccgctgga acacagcccc aacaacagtg actccatggc ctgcaactca ccgccgtcac 840 cagcactctg ggacacatct tcccattcca cgccagcccc tgcccgcaat ccgctgcccc 900 caccgctccc atacagtgcc tcccccaact acctggacga ccccaccaac tcctggtacc 960 acacacagaa cctcagtgga ccccacttac agcagcagcc tcctcagccg gctaccctgc 1020 accatgcctc ccctgggccc ccgcctaacc ctggggctgt gtactgagta cccacctggc 1080 ctgcgcccct ccacgaagga ccccctccag gaccaggcag aaggtgccct gtcctagcga 1140 cactcaggaa tcattgaggg gcacaggggg aaagactcoc ttccctctcc cttgtccctt 1200 cttccaggga cccaacaacc tccagataac aaatgcatgg accgaggatg ccccccaatc 1260 tccctcccct tgcttagact ggggtgccct ccagacggcg aggagttcta ccccagtggg 1320 gacagcacat gctctctgct ccaggaaccc ggattgcctc tagatggctc atcgctttcc 1380 agcttttcaa acacagtaga gacctccaaa atgggagcca gagtgtttgc aggtccacct 1440 gtgctggggc accaggcgcc acggattcca gcacagccag acctaaagca ccaaggggca 1500 actatacatt cttgagccac tctttaaaag acattggaca ttacatcatg gctgatcctc 1560 aagatggggg ggggctgacc tagtccccac tgttctccag ccctcattag gatttgaggg 1620 tccaaaccaa agaaaactcc cccaaatgag ggaacctttg atatccaggg cttccaaggg 1680 aagacttaaa ggagccatcc ctccgcccct tccctgggga aaaggattgt ccatgtcctt 1740 ttccaaggac ctgtttctcc ttccatgtac aggactttgc acaagtctgg ttttaaaagc 1800 tgttgaaacc taggacgaca atgggcattg ttaacagtta ggaccaaatc cactcctctc 1860 tgggcgggca gctctgctct gccctgaccc tgctcacccc ttcgttttgt tttgttttgt 1920 ttttctccca gtaagtttgc agtcttgggg gacgggctca aaccccaact ctctacagag 1980 atagaccagg caagaccccc cccactcaga cacccccttc gtggcagctt tggaaacagg 2040 ttgtccgttc tgctgcagga ttcaagtgag gatccaggag acaagaggag gcctagaact 2100 cagtgcctta ggggtaaggc tgtcagcttg gacggctggt accagtgcct ctccctggcc 2160 caggcatccc ccaaagctaa ctttcttctg ccccctgatg tggtaaaaca tcgaagaaag 2220 gagaggtgac agactgtagt tatatatata tagtatggtt tttttttgtt gttgttgttt 2280 cttttttttt tttttttttt agagcaacca agagaagcag gtcccctccc ttgtggtttc 2340 ctatttatgt gaccctgttc ctcctggacc aatctccctg tgttgcaagt cgaaagaggg 2400 atgtgggctc ctgctggatt tgggtttcgt gggaagtgaa ggagtaagaa gagacagacg 2460 tggtgggtct ccgagtccca ccccaaaggg acaggactga agccagctcc cacccctccc 2520 cagccttctc atttctgctt tcttactgga ccagtcttta tatataatgt taataaaaat 2580 taaaaaaaaa gaagaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa a 2631

<210> 2 <211> 232 <212> ADN <213> Homo sapiens <400> 2 tttacaaggg tcgcgctcca gcagtctcct ttgaagtcgt ttctgttatt catggggcca 60 cagtgttatt tcaaaggtgt cagccagcag gcttgaggct tttctggcat gaggtcactg 120 acagccctct ggacaacaca acttatttat tggtctctca ttctcccatc cccactcctc 180 ctttcttccc tctctccacc agagcgatcg cctcaccggc ccatcctcca ag 232

<210> 3 <211> 1551 <212> ADN <213> Homo sapiens <400> 3 cagaacccag cagccgtgta ccccgcagag ccgccagccc cgggcatgtt ccgagacttc 60 ggggaacccg gcccgagctc cgggaacggc ggcgggtacg gcggccccgc gcagcccccg 120 gccgcagcgc aggcagccca gcagaagttc cacctggtgc caagcatcaa caccatgagt 180 ggcagtcagg agctgcagtg gatggtacag cctcatttcc tggggcccag cagttacccc 240 aggcctctga cctaccctca gtacagcccc ccacaacccc ggccaggagt catccgggcc 300 ctggggccgc ctccaggggt acgtcgaagg ccttgtgaac agatcagccc ggaggaagag 360 gagcgccgcc gagtaaggcg cgagcggaac aagctggctg cggccaagtg caggaaccgg 420 aggaaggaac tgaccgactt cctgcaggcg gagactgaca aactggaaga tgagaaatct 480 gggctgcagc gagagattga ggagctgcag aagcagaagg agcgcctaga gctggtgctg 540 gaagcccacc gacccatctg caaaatcccg gaaggagcca aggaggggga cacaggcagt 600 accagtggca ccagcagccc accagcccoc tgccgccctg taccttgtat ctccctttcc 660 ccagggcctg tgcttgaacc tgaggcactg cacaccccca cactcatgac cacaccctcc 720 ctaactcctt tcacccccag cctggtcttc acctacccca gcactcctga gccttgtgcc 780 tcagctcatc gcaagagtag cagcagcagc ggagacccat cctctgaccc ccttggctct 840 ccaaccctcc tcgctttgtg aggcgcctga gccctactcc ctgcagatgc caccctagcc 900 aatgtctcct ccccttcccc caccggtcca gctggcctgg acagtatccc acatccaact 960 ccagcaactt cttctccatc cctctaatga gactgaccat attgtgcttc acagtagagc 1020 cagcttgggg ccaccaaagc tgcccactgt ttctcttgag ctggcctctc tagcacaatt 1080 tgcactaaat cagagacaaa atatttccca tttgtgccag aggaatcctg gcagcccaga 1140 gactttgtag atccttagag gbcctctgga gccctaaccc cttccagatc actgccacac 1200 tctccatcac cctcttcctg tgatccaccc aaccctatct cctgacagaa ggtgccactt 1260 tacccaccta gaacactaac tcaccagccc cactgccagc agcagcaggt gattggacca 1320 ggocattctg ccgccccctc ctgaaccgca cagctcagga ggcgcccttg gcttctgtga 1380 tgagctgatc tgcggatctc agctttgaga agccttcagc tccagggaat ccaagcctcc 1440 acagcgaggg cagctgctat ttattttcct aaagagagta tttttataca aacctaccaa 1500 aatggaataa aaggcttgaa gctgtgaaaa aaaaaaaaaa aaaaaaaaaa a 1551

<210> 4 <211> 1758 <212> ADN <213> Homo sapiens <400> 4 atggctcggc ctgacccatc cgcgccgccc tcgctgttgc tgotgctcct ggcgcagctg 60 gtgggccggg cggccgccgc gtccaaggcc ccggtgtgcc aggaaatcac ggrtgcccatg 120 tgccgcggca tcggctacaa cctgacgcac atgcccaacc agttcaacca cgacacgcag 180 gacgaggcgg gcctggaggt gcaccagttc tggccgctgg tggagatcca atgctcgccg 240 gacctgcgct tcttcctatg cactatgtac acgcccatct gtctgcccga ctaccacaag 300 ccgctgccgc cctgccgctc ggtgrtgcgag cgcgccaagg ccggctgctc gccgctgatg 360 cgccagtacg gcttcgcctg gcccgagcgc atgagctgcg accgcctccc ggtgctgggc 420 cgcgacgccg aggtcctctg catggattac aaccgcagcg aggccaccac ggcgcccccc 480 aggcctttcc cagccaagcc cacccttcca ggcccgccag gggcgccggc ctcggggggc 540 gaatgccccg ctgggggccc gttcgtgtgc aagtgtcgcg agcccttcgt gcccattctg 600 aaggagtcac acccgctcta caacaaggtg cggacgggcc aggtgcccaa ctgcgcggta 660 ccctgctacc agccgtcctt cagtgccgac gagcgcacgt tcgccacctt ctggataggc 720 ctgtggtcgg tgctgtgctt catctccacg tccaccacag tggccacctt cctcatcgac 780 atggacacgt tccgctatcc tgagcgcccc atcatcttcc tgtcagcctg ctacctgtgc 840 gtgtcgctgg gcttcctggt gcgtctggtc gtgggccatg ccagogtggo ctgcagccgc 900 gagcacaacc acatccacta cgagaccacg ggccctgcac tgtgcaccat cgtcttcctc 960 ctggtctact tcttcggcat ggccagctcc atctggtggg tcatcctgtc gctcaoctgg 1020 ttcctggccg ccgcgatgaa gtggggcaac gaggccatcg cgggctacgg ccagtacttc 1080 cacctggctg cgtggctcat ccccagcgtc aagtccatca cggcactggc gctgagctcc 1140 gtggacgggg acccagtggc cggcatctgc tacgtgggca accagaacct gaactcgctg 1200 cggcgottcg tgctgggccc gctggtgctc tacctgctgg tgggcacgct cttcctgctg 1260 gcgggcttcg tgtcgctctt ccgcatccgc agcgtcatca agcagggcgg caccaagacg 1320 gacaagctgg agaagctcat gatccgcatc ggcatcttca cgctgctcta cacggtcccc 1380 gccagcattg tggtggcctg ctacctgtac gagcagcact accgcgagag ctgggaggcg 1440 gcgctcacct gcgcctgccc gggccacgac accggccagc cgcgcgccaa gcccgagtac 1500 tgggtgctca tgctcaagta cttcatgtgc ctggtggtgg gcatcacgtc gggcgtctgg 1560 atctggtcgg gcaagacggt ggagtcgtgg cggcgtttca ccagccgctg ctgctgccgc 1620 ccgcggcgcg gccacaagag cgggggcgcc atggccgcag gggactaccc cgaggcgagc 1680 gccgcgctca caggcaggac cgggccgccg ggccccgccg ccacctacca caagcaggtg 1740 tccctgtcgc acgtgtag 1758

<210> 5 <211> 4877 <212> ADN <213> Mus musculus <400> 5 ctgggctgaa gctagaggcg accgatcgtg ggaaggggag gcagaaaggc taggaggagg 60 agggccgggg occaggccgc gcctccccga acccgccgcg cgcccccggg gtgggggagg 120 agcgcagggg acaggacaga ggggtccctc cccgaagcag agccgccctg cgcctcgtcc 180 ctgtgctgat ccccgccctc atccgaggct ggagcgcaga cccaccctcc caccgcggac 240 ccgcgacctc cccgacgccc ggcgacgccc tgaccctcgc tgctggtccg cgaactccct 300 aggctgatca ggacctgccc ctgtgccggc tgccacccgg acgccgcacg ccttcccagg 360 cgcccttttc cgagcagagg gaaagagaag atcgagcccc tctcagtgtg aatgcgccaa 420 cgggcggagc ggagcggagc ggacaccgcg cgcgggcatt gtgtgtgcgc gtgcagcgtg 480 gggtccgcag cggggagcac ccgcgggagg tcccgtttcc aaggggcgga gcgcagggct 540 tccagttctg ggctccctgt ccggacagag tcccagcgga gcccgaccgc tgcctaggcg 600 gcgggacggc gcgcctggcg gccaggaggg cgcactgaaa gaaggtcggc gagccctggt 660 ccccgcggtt cccgatcgag ttcctcttca gtccgcgaat ctgcgggaga ggttcgatcg 720 ccgacacagg gcgcggggag ccgggccgcc ccgtcggggg aatctgagac gtcctctggg 780 ctgcgtttga otgccgtgcc cgccgtgcac ggagcgcgtc cactçrtgtcc accgacccct 840 ttggtgtctg gtcctcgagt cctcacggcg tgcaccatga gcggcggcga agtggtttgc 900 tcgggatggc tccgcaagtc gcccccggag aagaagttga agcgttatgc gtggaagaga 960 aggtggtttg tgttgcgcag tggccgtttg actggagacc cggatgtcct ggagtattac 1020 aaaaacgatc atgccaagaa gcctattcgg attattgatt taaatttatg tcagcaagtt 1080 gatgctgggt tgacattcaa caaaaaggag tttgaaaaca gctatatctt tgatatcaac 1140 accatcgacc ggattttcta cttggtggca gatagtgagg aagacatgaa caagtgggtc 1200 cgttgtatct gtgacatctg tggattcaat cccacagaag aagatcctgt gaagccgctg 1260 actggctcct cacaagcacc cgtcgattca cctttcgcta taagtacagc accagcctcc 1320 agtcagatgg aagcttcttc agtcgcgcta cctcctcctt accaggtcat cagccttccg 1380 ccacaccoag acaccctcgg cctccaggac gatccacaag actacctctt gctgatcaac 1440 tgtcaaagca agaagcctga acctaacaga accctctttg actctgccaa gcccaccttt 1500 tctgagacag actgcaatga caacgtccct tcccaccaga ctcctgcttc ctcccagagc 1560 aaacacggaa tgaatggctt tttccagcaa caaatgatgt atgactgccc accgtcccgg 1620 ctgacatctg tctcgggaga gtccagcctc tataacctgc ccaggagcta ttcccatgac 1680 grtgttgccaa aggaatcccc atcaagcacg gaggccgacg gggagctgta cacctttaac 1740 accocatctg ggactgcagg tgtagaaacg cagatgagac atgtatccat cagttacgac 1800 attccgccaa cacctggcaa cacttaccag atcccacgga catttccaga aagcacactg 1860 ggacagtcat caaagctgga caccattcct gatatccccc cacctcggcc accaaagcca 1920 cafcccaactc atgaccggtc tcctgtggaa acgtgtggag tcccacgcac ggcctcggac 1980 actgacagca gttactgtat ccctcctcca gcaggcatga cgccctcccg gagtaatacc 2040 atttccaccg tggatttgaa caagttgcgg aaagatgcta gttctcaaga ttgctatgat 2100 attccacgga cctttccgag cgatagatct agttccctgg aaggcttcca tagccagtat 2160 aaaatcaaaa gcgtgttgac agcgggaggt gtctcgggtg aagagctgga tgagaactac 2220 gttcccatga accccaactc gccacctcga caacattccg gcagctttac cgagccaatc 2280 caggagccaa actatgtgcc aatgacccca gggacctttg acttttcttc ctttggaatg 2340 caagtccctc ctcctgctca tatgggcttc aggtccagcc caaagacccc tcccaggagg 2400 ccagttcctg ttgctgactg tgaaccaccc ccggtggata ggaacctcaa gccagacaga 2460 aaagtcaagc cggcaccttt agacataaaa cctctgtcag aatgggaaga gctgcaagcc 2520 ccagtcagat ctcccatcac caggagcttc gcfccgggact cctctaggtt tcccatgtcc 2580 cctcggcctg attctgtgca cagtacgaca tcgagcagcg actctcatga cagtgaagag 2640 aactatgtcc ccatgaatcc aaatctgtct ggcgaagacc cgaatctctt tgccagcaac 2700 agccttgatg ggggaagcag cccgatgaat aaacccaaag gagacaaaca agtcgaatac 2760 ctggatttag acctagattc tgggaagt.cc acgccaccac ggaagcaaaa gagcagtggt 2820 tctggcagca gcatggcaga cgagagggtg gattacgttg tggtggacca acagaagact 2880 ctggccctga agagtaccag agaagcttgg acggatggga ggcagtccac agagtccgag 2940 acacccacca agaatgtgaa gtgaagacat gccgtcgcct ctgccggcag acgagatctg 3000 agtggaaaga gagatgccaa gtgaagatgt tcccactctc agtggagcct cgagccagca 3060 ggggcagaga gaaggatctc tcacacatgt tcaagcaaat taggttgtga atggtgctgt 3120 gtggtattgg atttataacg tgtaaataac ccggggaaat agtgttttta gttcacagag 3180 aagcttctgt ccctaattaa cacacctgta gtattactat actgatgcac ttttcattta 3240 aaaccttggt ttgggtcttc ccgatctacc ttaacagact ttccttggga ggtcttttgg 3300 cctcctcaca ctactctata taacaatact aagtgaactg agctacttgt aattctggaa 3360 attccagttg aagctacagg gctaacacca ttaaaacaag aagtaagttg acacattcgc 3420 tfcbtctcttg aaggtggtag ccattagctt aagctgtaga acatagttgg acttgtcctt 3480 cgttgttttc caaaaattcc ggggatattg tatatagcag gtcaagacct agctctctga 3540 ctcatgtaca cttaggtttt aactgtagga ctttgttatt attatttttt ttgttaatga 3600 cagtgttggg ttcatcgtgt gaaggttctg ctgggtagga tcttgcacct ttcaaagact 3660 gcctcttagt tacactagta agcccccaaa tcatccacag catggactgc tggcctgctc 3720 ttactcctgt ttatgtgtta aaoattatct gcaaaaggca gattatacga ctgaccaatc 3780 aggtacgtac aaggcactga tgtgctaata cagtgattgg gtcagacaaa gtgcttcagt 3840 tagtgtgcgt tcgtcctaat cttggtttag aattaatgaa acagttggcg ttcactgtca 3900 gcagcatagt gtgattttga atgaattagg caggaattca agattactac tcttagctcg 3960 ctcgctctct ctctctctcc accgtagtgc tcttcctagg gttttctttc ttctacttaa 4020 tatcttcttg gccttatatt taaatcccta tgcaattaat gttttatatc tgcgttttta 4080 aaaaagaaat gtcattttaa gtgattcttg tatgtagcaa gcacctattg cttttgtgag 4140 taaatgaatt aagacttttg tactgtgatt tgtactcact gccccagttc cccaactgtt 4200 ggagccttgc tgctgtgaaa cgctgtagtc accatagttg tgtccaccac ccagccgggb 4260 ctgtgagtct cacctgtcac gtgacatcgt ctggtgtgga tgttggctct gaattagtgt 4320 cactgcagtt acacgtgtct gtctaggctt tgcaagatgc tgtagtcacc atagtcgtga 4380 ccaccaccta gccaggtctg tgagtctcac ctgtcacgtg ccatcatctg gtgtcactgc 4440 agttacacgt gtctgtctag gctttgccgc aaccttgaga agcagctagc attttccgtt 4500 gttcacacag taaggacaat gtctctgcat tgatctgagg ctcactggtg gcctggggaa 4560 gggacacaga gaacagaatg tctgcagctg aggcttgtct ctcttcgttc agacctctta 4620 cctgttgcct gagtacacaa tgcaccccgc tttctggccc actggccacg gtgctgtgcc 4680 taatctgagt tctcccctgg cttttccagt cagtttgaaa gctgtgttca taactagatg 4740 aagtgtagaa tagtaatatt agatgctttt aaatgttcgc ttctttttaa acaaaaacta 4800 aaacccagaa ctgaattttg aggtggattt ttaaataaaa aaagattgag tttgctgtga 4860 aaaaaaaaaa aaaaaaa 4877

<210> 6 <211> 2763 <212> ADN <213> Homo sapiens <400> 6 gagcctgctg ggacttgaac cagcagtaag attttcacga cacagtgctg tctgcttctc 60 cgtaagaagt tagaagccct agaaaacaat ctcctggtcc aaggtgcttg agtgggccga 120 tccagctata tcaagaacct ttgagaacaa aattctcaag catttctgag gggagtcgaa 180 taggtgaaaa ccttggctgg cctgacctta tcatggaacc tgacgacttt gattctgaag 240 acaaagagat attaagctgg gatattaatg atgtgaaact gccacagaac gtgaaaaaaa 300 ccgactggtt ccaggagtgg ccagattcct atgccaaaca catctacagc tcggaggaca 360 agaatgcgca gcggcacctg agcagctggg ccatgcgcaa taccaacaac cacaactccc 420 gcatcctcaa gaagtcctgc ctgggtgtgg tggtgtgcgg ccgcgactgt ctcgcagagg 480 aggggcgcaa gatctacctg agacctgcca tctgtgacaa ggcccggcag aagcagcagc 540 ggaaacgctg tcccaactgt gacgggcctc tgaagctcat cccttgccga ggtcatgggg 600 gcttcccggt caccaacttc tggaggcacg acggacgctt tatatttttc cagtcaaagg 660 gagagcatga tcatccaaaa ccagaaacca agttagaagc tgaggcaaga agagccatga 720 agaaagtgaa cacagcacct tcctccgtct cattgagcct gaaggggagc acagagacca 780 ggtctcttcc aggtgaaaca caaagtcagg ggagtttacc tttaacttgg tctttccagg 840 aaggcgtcca attgcctggt agttacagtg gacatttaat agctaacact cctcagcaga 900 actcactaaa tgattgcttt tccttctcca agagttatgg tctgggagga atcacagatc 960 tgactgacca gacttccact gtggacccca tgaagctcta tgaaaagcgc aaattgtcca 1020 gtagcagaac ctacagtagt ggagacctgc ttcctccttc tgcctccgga gtctactctg 1080 atcatggcga tctacaagcg tggagtaaaa atgctgcttt ggggagaaat catcttgctg 1140 acaactgtta ttccaattat ccttttcctc tgaccagctg gccttgcagc ttctctcctt 1200 cccaaaactc ttcagaaccc ttttaccago agcttccatt ggagccacct gcagccaaaa 1260 ctggctgtcc cccattatgg ccaaatccag cgggtaatct ttatgaagag aaagtacatg 1320 tggattttaa cagctacgtc cagtctcctg cataccattc acctcaagaa gacccctttc 1380 tcttcaccta cgcctctcat cctcatcagc aatattcact gccaagcaag agcagcaaat 1440 gggattttga ggaagaaatg acatacttgg gtttggatca ctgcaacaat gatatgcttc 1500 tgaacctgtg tcctttgaga tgacccaaat ctttcactat gtgcacccca gcccctcaaa 1560 aatggggaag ggctgaaaga atttccttag gaaataattt ttaaaacata accacagata 1620 aatgagaatc atgataagca gtagacaagg cttttttctt tttctttttt ccttcttttt 1680 tttttttttt ttttttttga gacagagtct tgctcttttg cccaggcagg aatgcagtgg 1740 cgccatctcg gctcactgca acctctgcct cccgggtttg agtgattctc ctgcgtcagc 1800 ctcccgagta gctgggatta caggcacctg ccactgcgcc tggctaattt ttctattttt 1860 agtagagaca gggttttgcc atgttggtca ggctgctctc aaactcctga tctcaagtga 1920 tctgcccacc tcaccatcco aaagtgctgg gattacaggc gtgagccatt gtgcccggct 1980 gacaaggctt ttttcttcac atgagtaatt tttttggctt cttctcctcc actctagtat 2040 ttccaccctc agtaaggaat ggaaacctgt cccgtctggg gtgtgaagtg ccctctgctt 2100 tttcccccac attgtttggg gttcccagca cctcagccac attgcatgct gggttttcat 2160 tgtcattgtt gcaaatgaaa tggagtagac atgtgaaatg ctaacctatc taggacctga 2220 tctatgcctt cttgggaact gagaatgaag aaacagaaat agatggtgga agaactgcct 2280 aaggtgtgaa aagctgaaga ttctaccact gaagtactga atatgttçrtc tagttgtgag 2340 actagtgtgt aaaatatatg ttttctagat gatttctgag acttgtgatg acaaggaacc 2400 tgacctaacc ccatttttca taaagacaaa gaacagcaat gttaaattgc catatgaaga 2460 gaaacactag tgatgtgcgt ggtctccttg cctcttgttt ccttccctct tcctcactga 2520 ottccccttg cacaggggct tctgttttat cccatttatt atttgtggca cctatatcaa 2580 tgtggggttt gtaataggtg agaaatattt gcttggagaa gctcttgtgc aattagcctg 2640 gcaatgattg gccggccatg tttgaatgcc agtttctctt ctttgctgaa gtactttatg 2700 afcaaaagtaa gcctagacat aaaatctgga gagaaccatg caataaacaa gtatttttga 2760 aat 2763 <210> 7 <211> 2641

<212> ADN <213> Mus musculus <400> 7 cgggaccctg gcgaggagcg gaagctaggt tgctctgttg cttctgcgat cgggcggcgg 60 cggcggcgag agcgagcggg gctgcggccg ggacggcggt cggggcagcg ggcgccgcag 120 tcagggagca gcagcgaggt tggcggctgc gggcggcagc gcagggcggg ccgggccggg 180 tgacggagtg gacggcgcgt cacgggtggc attgtgtgtc ccagtgtgca agaatagccc 240 cagaagagga aaggctgagc ccagagctct fccagcaggga agattccctt cccccctgct 300 tcaggctgct gagcactgag cggcgctcag aatggaagcc atcgccaaat atgacttcaa 360 agctactgct gacgatgagc tgagcttcaa aaggggggac atccttaagg ttttgaatga 420 agaatgtgac cagaactggt ataaggcaga actcaatggg aaagatggct tcatccccaa 480 gaattacata gaaatgaaac cacatccgtg gttttttggc aaaatcccca gagccaaggc 540 agaagaaatg ctcagcaaac agcggcatga cggggccttc ctgatccgag agagcgagag 600 cgctcctggg gacttctccc tgtccgtcaa gtttggaaat gatgtgcagc acttcaaggt 660 gctccgcgac ggagccggga agtatttcct çrtgggtggtg aagtttaatt ctttgaafcga 720 gctggtagat taccacagat caacatccgt gtccaggaac cagcagatat tcttacggga 780 catagaacag atgccacagc agccaaccta cgtccaggcg ctctttgact ttgaccccca 840 ggaggatggc gagctgggct ttcgcagagg agacttcatt catgtcatgg ataactcaga 900 tcccaattgg tggaaagggg cctgccacgg gcagaccggc atgtttcccc gcaattatgt 960 caccccagtg aaccggaacg tctaagaagc aaaagagatt atttaaagaa agtgaaaagt 1020 taagaccgtt cacaagaatt acacccacac gctgcctgtc acagcctgtg agggaacgca 1080 gaacacctgg ctgggtccca cgggtgaccc tctcattggg ttgcaacttt ggggggtggg 1140 gaggggtgtt tgatttcata atgccaaaac ttaacctatt gaatgaatta cagtttttat 1200 tacggaatct cgccgctacc cctgttcccc tcctgtgtcc tttttctcgt tctttctttc 1260 ctgtccagtg catgatgttt aaggccacat atagtccagc tgatgccaat aataaaagac 1320 aagaaaccaa gtgggctggt attttctcta tgcaaaatgt ctgtggagat ggatggactg 1380 aaagagccgg attcctcaca cacaggggca gccagtgctt ctggggccct ggttggggtt 1440 cacccgagat gcccaggggt accgcctcca gcctcaggoc tggagcattc catcaaagtt 1500 ggaattaggg gaaggaggcc cactgtcctc cccggtctcc tgagagtcag actgcaggcc 1560 ctoccctctc ccactgcttc ccttcaggtg ttttgacgtt tttttgtttg tttgtttçrtt 1620 ttttttaaat agtgcctttg tcttatttca agggtgttca taaatggtat ttgtaccatt 1680 tttttttttt aataagttaa agacagtcca gagcttttca gttgattcgt ctcctatcct 1740 gtgtaaatat tttcctctca gggcagggga aagaggacag agaaaggagc tggtagaagc 1800 agagagtgta tttcccatct tgaatgggcc ggaggtctcg aagcctcagc ttttactttg 1860 tgagctgcaa cactcgcttc agctcagact cagtggacat cagagtctct gtctccgtgt 1920 ctcagttatg gtctgctctc tctatgcctg gagctactga tccaaacaca agacggtcag 1980 aggagccctg gcatccttca ctcttatagg cctacatgca gatgggcttg aagagaattg 2040 gcctttcatt tttcacgctc gtatttcccc acctgtccaa gggtgcagat agcaggattg 2100 tggggtcggc cgcatttctc ttggcagtgg gttgtgctgc ccctcccccc accccacccc 2160 tccatcccac aaagcctttc gaggtaggag agaccaagac cagtgcacag ctttttaact 2220 cttgtcttct gtgagttttc cgtcctctgt agtcacgtgc ctgcacaccg ttctctccac 2280 cctgcctcct tcccacagca gaagcagggc tccacccagg ccttcccttg gagtcggtgc 2340 atccatgggc tgctagactc ttgcgggtag agtctcccct ggacttagca ttgtgagatg 2400 gactcagctc agggcgcccc taaggctcgg aggcggcctt ctgggtcccc acctctcctg 2460 gttccgctgc tgctctccct gctgatgata aagtaatctc tggagtcaca cctgggccat 2520 gtgattgttt tattttggaa ttggtgtata tcatgaagcc ttgctgaact aagttttgtg 2580 tgtatatatt taaagatcag tgtttaaata aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 2640 a 2641

<210> 8 <211> 2074 <212> ADN <213> Mus musculus <400> 8 agagacaggg tttctctgtg tagccctgga gtgctgggtt taaaggcata cctagtcctg 60 gttctgaact cttttttttt cttttaaaca tgtatgagtg ttttccctgc ttgtatgtct 120 ccatacagtc tatacacctg gcgccaggga aggccagaag aggatgttga ttcccctgga 180 actggagtta cagatggttg tgagacgcta tgtggatact gcaaattaaa cccaagtcct 240 cctaaaagca gcagcacctg ctctaaacca ctgcaccagc tctccagccc ctggtcctga 300 cctcctgatc accctgcctt gtcacctact agtttagcgt catgtctcag cttttcacat 360 agagaatttg ggaaagcaac aaacaaagta cagaatctga aagaaggttt tgggtaacag 420 gagttctggt gaacagggca aaccaattcc accaccatga gttggagctt cctgactcgc 480 ctgctagagg agatccacaa ccattcgaca tttgtaggga agatctggct cactgtgctg 540 attgtctttc gaattgtcct aactgctgta ggaggagagt ccatctacta tgatgaacaa 600 agcaaatttg tgtgcaacac agagcagccg ggctgtgaga atgtctgcta tgatgccttt 660 gccccgctct cccacgtgcg cttctgggta ttccagatca toctggttgc aactccctct 720 gtgatgtacc tgggatatgc tattcataag attgccaaaa tggagcatgg tgaggcagac 780 aagaaggcag ctcggagcaa accctatgcc atgcgttgga aacagcaccg ggctctggaa 840 gaaacggaag aggaccatga agaggatcct atgatgtatc cagagatgga gttagaaagc 900 gaaaaagaaa ataaagagca gagccaacca aaacctaagc atgatggccg acgacgaatt 960 cgagaggatg ggctcatgaa aatctatgtg ttgcagctgc tggccaggac tgtgtttgag 1020 gtgggctttc taatagggca gtatttcctg tatggcttcc aagtccaccc attttatgtg 1080 tgcagcagac ttccttgccc tcataagata gactgcttta tttctagacc cactgaaaag 1140 accatcttcc ttctgataat gtatggtgtc acaggcctct gcctattgct taacatttgg 1200 gagatgcttc acttagggtt tgggacaatt cgagactcac taaacagtaa aaggagggaa 1260 cttgatgatc cgggtgctta taattatcct ttcacttgga acacaccctc tgctccccct 1320 ggctataaca ttgctgtcaa accagatcag atccagtaca ctgagctgtc caatgctaag 1380 attgcctaca agcaaaacaa agccaatatt gcccaggaac agcagtacgg cagccacgag 1440 gaacacctcc cggctgatct ggagactctg cagcgggaga tcagaatggc tcaggaacga 1500 ttggacctag caatccaggc ctaccatcac caaaacaacc cccatggtcc tcgggaaaag 1560 aaggccaaag tggggtccaa atctgggtcc aacaaaagca gtattagtag caaatcaggg 1620 gatgggaaga cctccgtctg gabttaatct tggttgggct taaaacttgg gttttcatag 1680 tttatggtaa gcagcaactt gctgaataat gacttccatt gagtaaacat ttggctctgg 1740 ttatcttcag ggatgctgtt ggotcatgat ccaaactcag gggactctga aggtggagct 1800 gggatgagtc gggagaggga aacacagtgt tcccaggcac atgttctcag caataatgca 1860 gttgcagaac tttcaggttg tgtcttccag atccagagaa gaactgatat atttaaatca 1920 ttcttgttgg acagtttttg tatgtacagt attatggtac agttttttta gtatgataaa 1980 tttttttttt gtatttgtac attggactgc tgtagttaca cttttttata ttaaaggaaa 2040 aaatccttgt aaataaaaaa aaaaaaaaaa aaaa 2074 <210> 9 <211> 2281 <212> ADN <213> Mus sp. <400> 9 atgatgtggg ggaccaaact tctgccggtc ctgttgctgc agcatgtcct cctgcacctc 60 ctcctgcttc atgtcgccat cccctatgca gaaggacaga agaaaagaag aaatacactt 120 catgaattta aaaagtcagc aaaaactact cttaccaagg aagaeccatt actgaagatt 180 aaaaccaaaa aagtgaactc tgcagatgag tgtgccaaca ggtgtatcag gaacaggggc 240 tttacgttca cttgcaaggc cttcgttttt gataagtcaa gaaaacgatg ctactggtat 300 cctttcaata gtatgtcaag tggagtgaaa aaagggtttg gccatgaatt tgacctctat 360 gaaaacaaag actatattag aaactgcatc attggtaaag gaggcagcta taaagggacg 420 gtatccatca ctaagagtgg catcaaatgc cagccttgga attccatgat cccccatgaa 480 cacagctttt tgccttcgag ctatcgcggt aaagacctac aggaaaacta ctgtcgaaat 540 cctcgagggg aagaaggggg accctggtgt ttcacaagca atccagaggt acgctacgaa 600 gtctgtgaca ttcctcagtg ttcagaagtt gaatgcatga cctgcaatgg tgaaagctac 660 agaggtccca bggatcacac agaatcaggc aagacttgtc agcgctggga ccagcagaca 720 ccacaccggc acaagttctt gccagaaaga tatcccgaca agggctttga tgataattat 780 tgccgcaatc ctgatggcaa gccgaggcca tggtgctaca ctcttgaccc tgacacccct 840 tgggagtatt gtgcaattaa aacgtgcgct cacagtgctg tgaatgagac tgatgtccct 900 atggaaacaa ctgaatgcat tcaaggccaa ggagaaggtt acaggggaac cagcaatacc 960 attfcggaatg gaattccctg tcagcgttgg gattcgcagt accctcacaa gcatgatatc 1020 actcccgaga agttcaaatg caaggacctt agagaaaatt attgccgcaa tccagatggg 1080 gctgaatcac catggtgttt taccactgac ccaaacatcc gagttggcta ctgctctcaa 1140 attcccaagt gtgacgtgtc aagtggacaa gattgttatc gtggcaatgg gaaaaactac 1200 atgggcaact tatccaaaac aaggtctgga cttacatgtt ccatgtggga caagaatatg 1260 gaggatttac accgtcatat cttctgggag ccagatgcta gcaaattgaa taagaattac 1320 tgccggaatc ctgatgatga tgcocatgga ccttggtgct acacggggaa tcctcttatt 1380 ccttgggatt attgccctat ttcccgttgt gaaggagata ctacacctac aattctgaat 1440 ttggaccatc ctgtaatatc ctgtgccaaa acaaaacaac tgcgggttgt aaatggcatt 1500 ccaacacaaa caacagtagg gtggatggtt agtttgaaat acagaaataa acatatctgt 1560 ggaggatcat tgataaagga aagttgggtt cttactgcaa gacaatgttt tccagccaga 1620 aacaaagact tgaaagacta tgaagcttgg cttggcatcc acgatgttca tgagagaggc 1680 gaggagaagc gcaagcagat cttaaacatt tcccagctgg tctatggtcc tgaaggctca 1740 gacttggttt tactgaagct tgctcgacct gcaatcctgg ataactttgt cagtacaatt 1800 gatttaccta gttatggttg tacaatccct gaaaagacca cttgcagtat ttacggctgg 1860 ggctacactg gattgatcaa cgcggatggt ttattacgag tagotoatct gtatattatg 1920 gggaatgaga aatgcagtca gcaccatcaa ggcaaggtga ctttgaatga gtctgagtta 1980 tgtgctgggg ctgaaaagat tggatcagga ccatgtgagg gagattatgg tggcccactc 2040 atttgtgaac aacacaaaat gagaatggtt c11ggtgLca ttg Lfccctgg tcgtggatgt 2100 gccatcccaa atcgtcctgg tatttttgtt cgagtagcat attatgcaaa atggatacac 2160 aaagtaattt tgacatacaa gttgtaatag ccatagaaga ggccagtgtg tttgaagcat 2220 ccatggatac atgaggattt ccaagacttc aggattaaaa tgtcacctaa aacaatccta 2280 a 2281

<210> 10 <211> 2525 <212> ADN <213> Mus musculus <4 0 0> 10 gaçrtcacccc cgcgcagcct aggcttgccg tgcgagtcgg acttggtccg ggcccaccgc 60 cctgctctgt actactactc ggctttctcg tcaagatgcc tgaggaagtg caccatggag 120 aggaggaggt ggagaccttt gcctttcagg cagaaattgc ccagctcatg tccctcatca 180 tcaacacttt ctattcaaac aaggagattt tcctccgcga gttgatctct aatgcttcag 240 atgccctgga caagattcga tatgagagcc tgacggaccc ttctaagttg gacagtggga 300 aagagctgaa aattgacatc atccccaacc ctcaggagcg cacgctgact ttggtggaca 360 caggcattgg catgaccaag gctgacctca ttaataacct gggaaccatt gctaagtctg 420 gcacgaaggc gttcatggag gctctccagg ctggtgcaga catctccatg atcgggcagt 480 ttggtgtcgg attctactcg gcctatctag ttgcagagaa agtggttgtg atcaogaagc 540 acaatgatga tgagcagtat gcctgggagt cgtctgcggg tggctccttc accgtccggg 600 cagaccatgg tgagcccatt ggccggggta ccaaagtgat ccttcacctc aaagaagacc 660 agacagagta cttggaggag aggagggtca aggaagtggt gaagaaacat tcgcagttca 720 taggctatcc catcaccctc tatttggaga aggaacggga gaaggagatc agtgatgatg 780 aggcagagga agagaaaggt gagaaagagg aggaagataa ggaggatgag gagaagccta 840 agattgaaga tgtgggatcc gatgaggaag atgacagcgg caaagacaag aaaaagaaaa 900 caaagaagat caaagagaag tacattgacc aggaggagct gaacaagaca aagcctatct 960 ggaccagaaa cccggatgac atcacgcagg aggagtatgg cgaattctat aagagcctca 1020 ccaatgactg ggaggaccac ttggcagtca agoaottotc tgtagaaggt cagttggaat 1080 tcagggcatt gctcttcatt ccccggcggg ctoocttcga cctttttgag aacaagaaga 1140 agaagaacaa catcaaattg tatgtccgcc gtgtgttcat catggacagc tgtgacgagc 1200 tgatacctga gtacctcaac tttatccgcg gtgtggttga ctccgaggac ctgcccctga 1260 acatctcccg ggagatgctg cagcagagca agatcctgaa ggtcatccgc aagaacatcg 1320 tcaagaagtg cctggagctc ttctccgagc tggctgagga caaggagaac tacaagaagt 1380 tctatgaggc cttctccaaa aatttaaagc ttggaattca tgaagattcc actaaccgac 1440 gccgcctctc tgagctcctt cgctatcaca cctctcagtc tggagatgag atgacctcct 1500 tgtcagagta tgtgtctcgc atgaaggaga cccagaagtc catctactat atcactggtg 1560 agagcaaaga gcaagtggcc aactctgcct ttgtggagcg agtgcggaag cggggcttcg 1620 aggtggtgta tatgactgag cctattgacg agtactgcgt gcagcagctc aaggagtttg 1680 atgggaagag cctggtctca gtgactaagg agggcctgga gctaccagag gacgaggaag 1740 agaagaagaa aatggaggag agcaaggcaa agtttgagaa tctctgcaag ctcatgaagg 1800 agatcttgga caagaaggtt gaaaaggtga caatctccaa taggcttgtg tcttcaccct 1860 gctgcattgt gacaagcacc tatggctgga cagccaacat ggaacggatc atgaaggccc 1920 aggcactgcg agacaactct acaatgggct acatgatggc caaaaaacac ctggagatca 1980 accctgacca ccccatcgtg gagaccctgc ggcagaaggc tgaggcagac aaaaacgaca 2040 aagctgtcaa ggacctggtg gtgctgctgt ttgaaactgc tctgctctcc tctggtttct 2100 cacttgagga tccccaaacc cactccaacc gcatctaccg catgattaaa ctaggcctgg 2160 gcatcgatga agatgaggtc actgcagagg agcccagtgc tgctgttcct gatgagatcc 2220 cccctctgga aggcgatgag gatgcctcgc gcatggaaga ggtggattaa agcctcctgg 2280 aagaagccct gccctctgta tagtatcccc gtggctcccc cagcagccct gacccacctg 2340 gctctctgct catgtctaca agaatcttct atcctgtcct gtgccttaag gcaggaagat 2400 cccctcccac agatagcagg gttgggtgtt atgtattgtg gtttttttgt ttgttttatt 2460 ttgttctaaa attaaaagta tgcaaaataa agaagatgca gttttaaaaa aaaaaaaaaa 2520 aaaaa 2525

<210> 11 <211> 7037 <212> ADN <213> Homo sapiens <400> 11 gctgcgtgga gcggcggagc cggagggaag caaaggaccg tctgcgctgc tgtccccgcc 60 ccgcgcgctc tgcgcccctc gtccctggcg gtcgctccga agctcagccc tcttgcctgc 120 cccggagctg tcccgggcta gccgagaaga gagcggccgg caagtttggg cgcgcgcagg 180 cggcgggccg cgggcactgg gcgcctcgct ggggcggggg gaggtggcta ccgctcccgg 240 cttggcgtcc cgcgcgcact tcggcgatgg cttttccgcc gcggcgacgg ctgcgcctcg 300 gtccccgcgg cctcccgctt cttctctcgg gactcctgct acctctgtgc cgcgccttca 360 acctagacgt ggacagtcct gccgagtact ctggccccga gggaagttac ttcggcttcg 420 ccgtggattt cttcgtgccc agcgcgtctt cccggatgtt tcttctcgtg ggagctccca 480 aagcaaacac cacccagcct gggattgtgg aaggagggca ggtcctcaaa tgtgactggt 540 cttctacccg ccggtgccag ccaattgaat ttgatgcaac aggcaataga gattatgcca 600 aggatgatcc attggaattt aagtcccatc agtggtttgg agcatctgtg aggtcgaaac 660 aggataaaat tttggcctgt gccccattgt accattggag aactgagatg aaacaggagc 720 gagagcctgt tggaacatgc tttcttcaag atggaacaaa gactgttgag tatgctccat 780 gtagatcaca agatattgat gctgatggac agggattttg tcaaggagga ttcagcattg 840 attttactaa agctgacaga gtacttcttg gtggtcctgg tagcttttat tggcaaggtc 900 agcttatttc ggatcaagtg gcagaaatcg tatctaaata cgaccccaat gtttacagca 960 tcaagtataa taaccaatta gcaactcgga ctgcacaagc tat.tttt.gat gacagctatt 1020 tgggttattc tgtggctgtc ggagatttca atggtgatgg catagatgao tttgtttcag 1080 gagttccaag agcagcaagg actttgggaa tggtttatat ttatgatggg aagaacatgt 1140 cctccttata caattttact ggcgagcaga tggctgcata tttcggattt tctgtagctg 1200 ccactgacat taatggagat gattatgcag atgtgtttat tggagcacct ctcttcatgg 1260 atcgtggctc tgatggcaaa ctccaagagg tggggcaggt ctcagtgtct ctacagagag 1320 cttcaggaga cttccagacg acaaagctga atggatttga ggtctttgca cggtttggca 1380 gtgccatago tcctttggga gatctggacc aggatggttt caatgatatt gcaattgctg 1440 ctccatatgg gggtgaagat aaaaaaggaa ttgtttatat cttcaatgga agatcaacag 1500 gcttgaacgc agtcccatct caaatccttg aagggcagtg ggctgctcga agcatgccac 1560 caagctttgg ctattcaatg aaaggagcca cagatataga caaaaatgga tatccagact 1620 taattgtagg agcttttggt gtagatcgag ctatcttata cagggccaga ccagttatca 1680 ctgtaaatgc tggtcttgaa gtgtacccta gcattttaaa tcaagacaat aaaacctgct 1740 cactgcctgg aacagctctc aaagtttcct gttttaatgt taggttctgc ttaaaggoag 1800 atggcaaagg agtacttccc aggaaactta atttccaggt ggaacttctt ttggataaac 1860 tcaagcaaaa gggagcaatt cgacgagcac tgtttctcta cagcaggtcc ccaagrtcact 1920 ccaagaacat gactatttca agggggggac tgatgcagtg tgaggaattg atagcgtatc 1980 tgcgggatga atctgaattt agagacaaac tcactccaat tactattttt atggaatatc 2040 ggttggatta tagaacagct gctgatacaa caggcttgca acccattctt aaccagttca 2100 cgcctgctaa cattagtcga caggctcaca ttctacttga ctgtggtgaa gacaatgtct 2160 gtaaacccaa gctggaagtt tctgtagata gtgatcaaaa gaagatctat attggggatg 2220 acaaccctct gacattgatt gttaaggctc agaatcaagg agaaggtgcc tacgaagctg 2280 agctcatcgt ttccattcca ctgcaggctg atttcatcgg ggttgtccga aacaatgaag 2340 ccttagcaag actttcctgt gcatttaaga cagaaaacca aactcgccag gtggtatgtg 2400 accttggaaa cccaatgaag gctggaactc aactcttagc tggtcttcgt ttcagtgtgc 2460 accagcagtc agagatggat acttctgtga aatttgactt acaaatccaa agctcaaatc 2520 tatttgacaa agtaagccca gttgtatctc acaaagttga tcttgctgtt ttagctgcag 2580 ttgagataag aggagtctcg agtcctgatc atatctttct tccgattcca aactgggagc 2640 acaaggagaa ccctgagact gaagaagatg ttgggccagt tgttcagcac atctatgage 2700 tgagaaacaa tggtccaagt tcattcagca aggcaatgct ccatcttcag tggccttaca 2760 aatataataa taacactctg ttgtatatcc ttcattatga tattgatgga ccaatgaact 2820 gcacttcaga tatggagatc aaccctttga gaattaagat ctcatctttg caaacaactg 2880 aaaagaatga cacggttgcc gggcaaggtg agcgggacca tctcatcact aagcgggatc 2940 ttgccctcag tgaaggagat attcacactt tgggttgtgg agttgctcag tgettgaaga 3000 ttgtctgcca agttgggaga ttagacagag gaaagagtgc aatcttgtac gtaaagtcat 3060 tactgtggac tgagactttt atgaataaag aaaatcagaa tcattcctat tctctgaagt 3120 cgtctgcttc atttaatgtc atagagtttc ettataagaa tcttccaatt gaggatatca 3180 ccaactccac attggttacc actaatgtca cctggggcat tcagccagcg cccatgcctg 3240 tgcctgtgtg ggtgatcatt ttagcagttc tageaggatt gttgctactg gctgttttgg 3300 tatttgtaat gtacaggatg ggctttttta aacgggtccg gccacctcaa gaagaacaag 3360 aaagggagca gcttcaacct catgaaaatg gtgaaggaaa ctcagaaact taactgcagt 3420 ttttaagtta tgctacatct tgacccacta gaattagcaa etttattata gatttaaact 3480 ttcttcatga ggagtaaaaa tccaaggctt tactgctgat agtgctaatt ggcattaacc 3540 acaaaatgag aattatattt gtcaaccttc teettataaa taagttcaga catacattta 3600 ataacatagg gtgacttgtg tttttaggta tttaaataat aaaatttcaa gggatagttt 3660 ttattoaatg tatataagac aggtagtgcc tgatttacta ctttatataa aatagtacct 3720 ccttcagtta ctgtttctga tttaatgtac ggaactttat ttgttgttgt tgttgttgtt 3780 gttgttgttg ttttaaagca gtccaaattt ggaccttagc aatcatgtct tttgtatagg 3840 tacttaatgt taatacatat tacactacag tttacttttc agaatactaa agactttata 3900 actgcatgaa cttggatttt tttaatcact catatggtag aattttataa acacatacat 3960 gataccatcc aaattcttgc ttttaataac aaaggtacaa tattttgttt tagtatgaaa 4020 atctggtaga tcctattaca cttctgttta tattaaatcc acaatatttt attacatttt 4080 taacttgtat aaattttagg tcaaatcctt caagccaacc tatactaaaa attagttcca 4140 taatcacaaa tggctctttt gtgtaattgt ttaatttcac ctgaatatca taatgcttaa 4200 agccatatgg agttggaaat tatttccaaa gcatatttat tccattgttt tagtctggct 4260 atttacagta taaaaaaagc atttttatta aaatactgtg tagttctttg agatagttgc 4320 ttatgcatat agtaagtatt acattcttag agtagagcag agtttttagt tagtattaat 4380 ttattttcct ccattcatgt acttttcctt atatttccaa aactgttact gagaatgggt 4440 caagatcagt gagaaatctt tacagttgac aggaacctgg accccttacc ccaactttat 4500 gagtaatgct tggaataaaa actcttaagg caactcactg atttacttct agcaatagca 4560 tgatgttaca ggaatattac ctctgtttaa gcaaggtaat gtgtaaaatc agtctcggct 4620 gtcagaataa cttctaaaag gtatttttat aagcagttca agttactgaa aaccttttaa 4680 acctttctga agttcgttag tataaattac ttttctagga ttattaataa aagccacata 4740 ggtggcaagt tgtagtttta tatggctctg tagagtggtg aaccttctag aggaatatat 4800 gatttattca cagttcctca aggcctgggg atgatgatca gttataccta tttttgtgca 4860 attacatcat gttgtacatt agaaatggag agtttaatag ctctttaact gctgtcctca 4920 ttaggtaatg ataaatattt cccttaaata attgactatt ttgctgtgtt ttaaaaatga 4980 ttgaaattta tcttgccata tctcataatt tcatgcacaa gttgactgag ctaatcttga 5040 gaatatattc gtaaaatagg agcacattta gttgaggtat acaaggtagg actctagaca 5100 aaaccttcta ttttagcttt agtgaatttc aaaagtaatg ggtcttggag tatagatttt 5160 tattagtagc ttgaaagagc ttaatcatat gcagtaagta tttttattac caataaattt 5220 aaaatttttt aagaaaaata tttttatcct agggccaagt gttgcctgcc accaatcagt 5280 aagttagrtct ataacaaatt ttaccctaac agttttacca cctagtaaca gtcatttctg 5340 aaaatatgtt ggatagaaag tcactctttg gcaaaagtgt tagaatttgc ttttgtgcca 5400 tctattcctt ttatggcatc tatcttgaaa gtaatcttgt attggagatt gaaagatgct 5460 gtaatttaga aattaacatg atatcttaaa ttacctttat gaaatatagt tttgtataat 5520 agcatagatt ttccttcaaa aaatgaacat ttatatatct acaaaaatat ggagaagagt 5580 aatttgaaag cctactttct gaagaaaatg gtgggatttt tttttatcat gattaaatat 5640 caaaaaattg ccctatgaaa actttaaatc tctaaaacat ttgaaatact accatatttg 5700 tgatttattg agaataaaaa tccattttga aatgtaaaat ttttatgatc tgattcagtt 5760 ttaagaaaac atgaatgaac tagaagatat taaaaacatt tgacattggt aagaaatatt 5820 gatactgata ttgattttta tataggtatt tatttcagaa ttgatatttt gagaaaaata 5880 catgtgagtc attttttctg tttctctttt ctcttaacga ttatcactgt aattctgaat 5940 ctgaaaggta aaacaattag tcaaaatatt attgccatca ttctacctgt gttatgaaac 6000 tacttattca tagttaattc tcattaacac ttacatttcc ataaagaaaa ctcaagtatt 6060 aataaaagag actttactgg cttaagaggg ctgtgaaaga tttttgatag tgaatcatga 6120 ccctaaggga gagatttgtg tgataaaagt attgtatata atagatcagc gatttttgta 6180 aggcaaacag aatttgtaag ttggcagatc ttcctaagtt gcaaaatgta atgatgagct 6240 tggtggagaa gaatgagtcg ttcttggaat acctatgtgc agccactacc catctcaatg 6300 tcaccttgtt tgcattcttg gatagcttgt atatgtagta gtttgatgaa taatttaaag 6360 aaaaacacct aaaatttgaa aaatgattgt aggatcaaaa aaggcagatg aaattactta 6420 atactcaçrtg ttttggagag tattcctttt agtttgttgg ttggctggtt tgaacgatag 6480 aaatatgcag catgcaatat atgcttatat ttcattttaa tttctgatat ataatgaact 6540 tcttgggaga ggtactgaat ctttgatgtt ttttgtcatt gttctcaagt gcaatataac 6600 aatgtaacca aatctagata atttcaaagt tgtcattaat ttagtaagcc taatataaac 6660 aaatatttgt attatttttg ttagcaggaa agagtgatta agtgaggtta tttaccceta 6720 aatggtccat tctgcattgt atttcaggct ggaaatgaat tattctttac cagttttgaa 6780 acactttgaa atatoctaag gtaacttgga agctgtgtag tatatcaaat taatttgcta 6840 cctaataaca tagaaagtaa atatctttgt ggtcacccac attgggtgag acagaaaatg 6900 aatctgttct aaaatttgta atttgctaac ttgatttgag ttagtgaaaa ctggtacagt 6960 gttctgcttg atttacaaca tgtaacttgt gactgtacaa taaacataag catatggtac 7020 caaaaaaaaa aaaaaaa 7037 <210> 12 <211> 1572 <212> ADN <213> Danio rerio <400> 12 gccagaagag ctgtttgtaa ataaccgtct gggaagacac tttttggacg tcagctgtca 60 agagaaaaca cctgtcgaat tggtacagta aactattttg gaagtttctt ctttttttgc 120 tctcttttgc ctgatgtaat ataacggaga gaacttgcgg actttagtca gcttcagtac 180 gtcccaacgt aatctctgtt cacatgtcaa caaaaatgga gcaaccgttt tatgacgact 240 cgtttctttc tgcttatggt catccagacg ctgccctgca cgactacaag ctcctaaagc 300 agaacatgag cgtgagcttc gccgaaccct accggaacct caagaccctc cgctccgaaa 360 tcgacttcta cacagcggcg accggagacg tgggctcgct gaaactcgcc tctccggagc 420 tggagagact catcatccag aacggtaacg gcgtcatcac atcacccacg ccggggcagt 480 atttgtacgg tcggagcatc acagaggagc aagagggctt cgcggacgga ttcgtcaaag 540 cgctggacga gctccacaaa atgaaccaaa tgcccccgcc gaacgtgtcc atcggagccc 600 ccggggtgtc gagttgttcg gtggcgtcgt cagtcttcgg cgcctcctta ccgcccgaga 660 ctccggtgta caccaccctg aacagctgca atcctaacac taacctcaca cctgcagcca 720 actacccgac agccaccatc agctacctgc ctcaccatca ccaccaccag cagtaccacc 780 accatcacca ccagcccacg ccgcatcctc atcacttcca gcactcgctc catccgcagc 840 ggctcgttac tctgaaagag gagccacaga ccgtccccga cctgcagagc agcgatggtt 900 ctcctcccat gtcgcccatc gacatggagg accaggagcg catcaaagcg gagcgcaaga 960 ggctccggaa ccgactggcg gccaccaagt gccggcgacg gaagctggag cgcatctccc 1020 ggctggagga caaagtgaaa gtgctcaagt cggataacgc cggactgtcc agcactgcgt 1080 ccctgctgag ggagcaggta gctcagctta agcagaaggt catgacccat gtgagcagcg 1140 ggtgccagct gatgctgacg cccaagatca agtcgtttta ggggggagag ggatgctacg 1200 gactctggga aacactggaa gagcagatcc tgtttgtgat gatgttattg tcgcagcact 1260 gagtacgagc gttgtatatt tcttaagtgt tttcttgtag aaaactttaa tgttattgtt 1320 gttttccaaa gataaggtac tttcagccga acggacaatg gactaaactt ttgaagtgaa 1380 cagttttggt tttgttgtta agtgctgccc tttgaaaaca ttccagtaag ttattgatat 1440 tgtgagtcag gttgagccag acctttaaot gtttttctgt ttgtttgttt ttgtttattt 1500 tttatattta agtaaaaatg ttgaaaatga aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 1560 aaaaaaaaaa aa 1572

<210> 13 <211> 5252 <212> ADN <213> Homo sapiens <400> 13 ctctctccca gaacgtgtct ctgctgcaag gcaccgggcc ctttcgctct gcagaactgc 60 acttgcaaga ccattatcaa ctcctaatco cagctcagaa agggagcctc tgcgactcat 120 tcatcgccct ccaggactga ctgcattgca cagatgatgg atatttacgt atgtttgaaa 180 cgaccatcct ggatggtgga caataaaaga atgaggactg cttcaaattt ccagtggctg 240 ttatcaacat ttattcttct atatctaatg aatcaagtaa atagccagaa aaagggggct 300 cctcatgatt tgaagtgtgt aactaacaat ttgcaagtgt ggaactgttc ttggaaagca 360 ccctctggaa caggccgtgg tactgattat gaagtttgca ttgaaaacag grtcccgttct 420 tgttatcagt tggagaaaac cagtattaaa attccagctc tttcacatgg tgattatgaa 480 ataacaataa attctctaca tgattttgga agttctacaa gtaaattcac actaaatgaa 540 caaaacgttt ccttaattcc agatactcca gagatcttga atttgtctgc tgatttctca 600 acctctacat tatacctaaa gtggaacgac aggggttcag ttttfcccaca ccgctcaaat 660 gttatctggg aaattaaagt tctacgtaaa gagagtatgg agctcgtaaa attagtgacc 720 cacaacacaa ctctgaatgg caaagataca cttcatcact ggagttgggc ctcagatatg 780 cccttggaat gtgccattca ttttgtggaa attagatgct acattgacaa tcttcatttt 840 tctggtctcg aagagtggag tgactggagc cctgtgaaga acatttcttg gatacctgat 900 tctcagacta aggtttttcc tcaagataaa gtgatacttg taggctcaga cataacattt 960 tgttgtgtga gtcaagaaaa agtgttatca gcactgattg gccatacaaa ctgccccttg 1020 atccatcttg atggggaaaa tgttgcaatc aagattcgta atatttctgt ttctgcaagt 1080 agtggaacaa atgtagtttt tacaaccgaa gataacatat ttggaaccgt tatttttgct 1140 ggatatccac cagatactcc tcaacaactg aattgtgaga cacatgattt aaaagaaatt 1200 atatgtagtt ggaatccagg aagggtgaca gcgttggtgg gcccacgtgc tacaagctac 1260 acttfcagttg aaagtttttc aggaaaatat gttagactta aaagagctga agcacctaca 1320 aacgaaagct atcaattatt atttcaaatg cttccaaatc aagaaatata taattttact 1380 ttgaatgctc acaatccgct gggtcgatca caatcaacaa ttttagttaa tataactgaa 1440 aaagtttatc cccatactcc tacttcattc aaagtgaagg atattaattc aacagctgtt 1500 aaactttctt ggcatttacc aggcaacttt gcaaagatta attttttatg tgaaattgaa 1560 attaagaaat ctaattcagt acaagagcag cggaatgrtca caatcaaagg agtagaaaat 1620 tcaagttatc ttgttgctct ggacaagtta aatccataca ctctatatac ttttcggatt 1680 cgttgttcta ctgaaacttt ctggaaatgg agcaaatgga gcaataaaaa acaacattta 1740 acaacagaag ccagtccttc aaaggggcct gatacttgga gagagtggag ttctgatgga 1800 aaaaatttaa taatctattg gaagccttta cccattaatg aagctaatgg aaaaatactt 1860 tcctacaatg tatcgtgttc atcagatgag gaaacacagt ccctttctga aatccctgat 1920 cctcagcaca aagcagagat acgacttgat aagaatgact acatcatcag cgtagtggct 1980 aaaaattctg tgggctcatc accaccttcc aaaatagcga gtatggaaat tccaaatgat 2040 gatctcaaaa tagaacaagt tgttgggatg ggaaagggga ttctcctcac ctggcattac 2100 gaccccaaca tgacttgcga ctacgtcatt aagtggtgta actcgtctcg gtcggaacca 2160 tgccttatgg actggagaaa agttccctca aacagcactg aaactgtaat agaatctgat 2220 gagtttcgac caggtataag atataatttt ttcctgtatg gatgcagaaa tcaaggatat 2280 caattattac gctccatgat tggatatata gaagaattgg ctcccattgt tgcaccaaat 2340 tttactgttg aggatacttc tgcagattcg atattagtaa aatgggaaga cattcctgtg 2400 gaagaactta gaggcttttt aagaggatat ttgttttact ttggaaaagg agaaagagac 2460 acatctaaga tgagggtttt agaatcaggt cgttctgaoa taaaagttaa gaatattact 2520 gacatatccc agaagacact gagaattgct gatcttcaag gtaaaacaag ttaccacctg 2580 gtcttgcgag cctatacaga tggtggagtg ggcccggaga agagtatgta tgtggtgaca 2640 aaggaaaatt ctgtgggatt aattattgcc attctcatcc cagtggcagt ggctgtcatt 2700 gttggagtgg bgacaagtat ccttbgctat cggaaacgag aatggattaa agaaaccttc 2760 taccctgata ttccaaatcc agaaaactgt aaagcattac agtttcaaaa gagtgtctgt 2820 gagggaagca gtgctcttaa aacattggaa atgaatcctt gtaccccaaa taatgttgag 2880 gttctggaaa ctcgatcagc atttcctaaa atagaagata cagaaataat ttccccagta 2940 gctgagcgtc ctgaagatcg ctctgatgca gagcctgaaa accatgtggt tgtgtcctat 3000 tgtccaccca tcattgagga agaaatacca aacccagccg cagatgaagc tggagggact 3060 gcacaggtta tttacattga tgttcagtcg atgtatcagc ctcaagcaaa accagaagaa 3120 gaacaagaaa atgaccctgt aggaggggca ggctataagc cacagatgca cctccccatt 3180 aattctactg tggaagatat agctgcagaa gaggacttag ataaaactgc gggttacaga 3240 cctcaggcca atgtaaatac atggaattta gtgtctccag actctcctag atccatagac 3300 agcaacagtg agattgrtctc atttggaagt ccatgctcca ttaattcccg acaatttttg 3360 attcctccta aagatgaaga ctctcctaaa tctaatggag gagggtggtc ctttacaaac 3420 ttttttcaga acaaaccaaa cgattaacag tgtcaccgtg tcacttcagt cagccatctc 3480 aataagctct tactgctagt gttgctacat cagcactggg cattcttgga gggatcctgt 3540 gaagtattgt taggaggtga acttcactac atgttaagtt acactgaaag ttcatgtgct 3600 tttaatgtag tctaaaagcc aaagtatagt gactcagaat cctcaatcca caaaactcaa 3660 gattgggagc tctttgtgat caagccaaag aattctcatg tactctacct tcaagaagca 3720 tttcaaggct aatacctact tgtacgtaca tgtaaaacaa atcccgccgc aactgttttc 3780 tgttctgttg tttgtggttt tctcatatgt atacttggtg gaattgtaag tggatttgca 3840 ggccagggag aaaatgtcca agtaacaggt gaagtttatt tgcctgacgt ttactccttt 3900 ctagatgaaa accaagcaca gattttaaaa cttctaagat tattctcctc tatccacagc 3960 attcacaaaa attaatataa tttttaatgt agtgacagcg atttagtgtt ttgtttgata 4020 aagtatgctt atttctgtgc ctactgtata atggttatca aacagttgtc tcaggggtac 4080 aaactttgaa aacaagtgtg acactgacca gcccaaatca taatcatgtt ttcttgctgt 4140 gataggtttt gcttgccttt tcattatttt ttagctttta tgcttgcttc cattatttca 4200 gttggttgcc ctaatattta aaatttacac ttctaagact agagacccac attttttaaa 4260 aatcatttta ttttgtgata cagtgacagc tttatatgag caaattcaat attattcata 4320 agcatgtaat tccagtgact tactatgtga gatgactact aagcaatatc tagcagcgtt 4380 agttccatat agttctgatt ggatttcgtt cctcctgagg agaccatgcc gttgagcttg 4440 gctacccagg cagtggtgat ctttgacacc ttctggtgga tgttcctccc actcatgagt 4500 cttttcatca tgccacatta tctgatccag tcctcacatt tttaaatata aaactaaaga 4560 gagaatgctt cttacaggaa cagttaccca agggctgttt cttagtaact gtcataaact 4620 gatctggatc catgggcata cctgtgttcg aggtgcagca attgcttggt gagctgtgca 4680 gaattgattg ccttcagcac agcatcctct gcccaccctt gtttctcata agcgatgtct 4740 ggagtgattg tggttcttgg aaaagcagaa ggaaaaacta aaaagtgtat cttgtatttt 4800 ccctgccctc aggttgccta tgtattttac cttttcatat ttaaggcaaa agtacttgaa 4860 aattttaagt gtccgaataa gatatgtctt ttttgtttgt tttttttggt tggttgtttg 4920 ttttttatca tctgagattc tgtaatgtat ttgcaaataa tggatcaatt aatttttttt 4980 gaagctcata ttgtatcttt ttaaaaacca tgttgtggaa aaaagccaga gtgacaagtg 5040 acaaaatcta tttaggaact ctgtgtatga atcctgattt taactgctag gattcagcta 5100 aatttctgag ctttatgatc tgtggaaatt tggaatgaaa tcgaattcat tttgtacata 5160 catagtatat taaaactata taatagttca tagaaatgtt cagtaatgaa aaaatatatc 5220 caatcagagc catcccgaaa aaaaaaaaaa aa 5252 <210> 14 <211> 1718

<212> ADN <213> Mus musculus <4 0 0> 14 gcggcggcgg ctccgggggg cgggggcggg gagcccaggg gaactgctgg ggtcgtcccg 60 gtggtccccg gggaggtgga ggtggtgaag gggcagccat tcgatgtggg cccacgctac 120 acgcagctgc agtacatcgg cgagggcgcg tacggcatgg tcagctcagc ttatgaccac 180 gtgcgcaaga ccagagtggc catcaagaag atcagcccct ttgagcatca aacctactgt 240 cagcgcacgc tgagggagat ccagatcttg ctgcgattcc gccatgagaa tgttataggc 300 atccgagaca tcctcagagc gcceaeectg gaagccatga gagatgttta cattgttcag 360 gacctcatgg agacagacct gtacaagctg cttaaaagcc agcagctgag caatgaccac 420 atctgctact tcctctacca gatcctccgg ggcctcaagt atatacactc agccaatgtg 480 ctgcaccggg acctgaagcc ttccaatctg cttatcaaca ccacctgcga ccttaagatc 540 tgtgattttg gcctggcccg gattgctgac ccbgagcacg accacactgg ctttctgacg 600 gagtatgtgg ccacacgctg gtaccgagcc ccagagatca tgcttaattc caagggctac 660 accaaatcca tcgacatctg gtctgtgggc tgcattctgg ctgagatgct ctccaaccgg 720 ccoatcttcc ooggcaagca ctacctggao cagotoaacc acattctagg tatcttgggt 780 tccccatccc aggaggacct taattgcatc attaacatga aggcccgaaa ctacctgcag 840 tctctgccct cgaaaaccaa ggtggcttgg gccaagctct ttcctaaatc tgactccaaa 900 gctcttgacc tgctggaccg gatgttaacc ttcaacccaa acaagcgcat cacagtagag 960 gaagcgctgg ctcaccctta cctggaacag tactacgatc cgacagatga gccagtggcc 1020 gaggagccat tcaccttcga catggagctg gatgacctcc ccaaggagcg gctgaaggag 1080 ttgatcttcc aggagacagc ccgcttccag ccaggggcgc cagagggccc ctaacaagaa 1140 cagacacccc tgtccttttg gatctggtcc tgctcctacc tgctccttct ctgcagattg 1200 ttagaaagtg aactttgctc aacccagacc ccggcagccc aggctggacc aagggtgggc 1260 ctggccacct tctctcactt tgctggggtc tcotgcttca agcaggcttc tcccactcca 1320 tcccctgccc catctcccca tagcctgagt gatgaggtgg ccccagagct gatctctgct 1380 gctgtgtctt atctaccctt gctagccccg gctctggtag accgttctgg aatggagggg 1440 ctatgatcgt cctaggacct gtgctacgga ggggtggagg gcactgagta gggctctgcc 1500 ctatttcatc ttgttggaac cccaccccat tttccctgac agaacattcc taagtctcaa 1560 gggctagttt ccctgaggag cccaggccta accctctctc tctcaagctg ccacatgtaa 1620 cgcccttgct gcttctgtgt gtgggtgatt ggatgtgggg gtggggoccg tggagagccg 1680 gtgcccctcc ccatctcccc gtgcctgcct gtatctaa 1718 <210> 15 <211> 1272 <212> ADN <213> Bos taurus <4 0 0> 15 ggcgtccccg gctctcccga gcggcggcct ccccgctcct ttccggccag cggaggcagc 60 ttgcggcggc cggtcccccg gaggcgcggc gtcggccgag cggcggcgcg gagcgtcgag 120 cgcagcgcgg cggcggcggc ggeccggcag ceaacatggc ggcggcggcg gcggcgggcg 180 cgggcccgga gatggtccgc gggcaggrtgt tcgacgtggg gccgogctac accaatctct 240 cgtacatcgg cgagggcgcc tacggcatgg tgtgctctgc ttatgacaat gtcaacaaag 300 tccgagtcgc catcaagaaa atcagccctt ttgagcacca gacgtactgc cagagaacgc 360 tgagagagat aaagatctta ctgcgcttca gacatgagaa catcatcgga atcaatgaca 420 ttattcgagc accgaccatc gagcagatga aagatgtgta tatagtacag gacctcatgg 480 aaacagatct ctacaagctc ttgaagacgc aacacctcag caacgaccac atctgctatt 540 ttctctacca gatcctcaga gggttaaagt atattcattc agccaacgtg ctgcaccgtg 600 acctcaaacc ttccaacctg ctgctcaaca ccacctgcga tctcaagatc tgtgactttg 660 gcttggcccg tgttgcagat ccagaccacg accacacagg gttcttgaca gagtacgtgg 720 ccactcgctg gtaccgggct ccagaaatca tgttgaattc caagggctac accaagtcca 780 tcgacatctg gtccgtcggc tgcatcctcg cggagatgct ctccaacagg cccatcttcc 840 ccgggaagca ctaccttgac cagctgaacc acattctggg tattcttgga tccccgtcgc 900 aggaagacct gaattgtata ataaatttaa aagcfcagaaa ctacctgctc tctcttccac 960 acaaaaataa ggtgccatgg aacaggctgt tcccgaacgc ggactccaaa gctctggatc 1020 tactggacaa aatgttgacg ttcaaccctc acaagaggat cgaggtggag caggctctgg 1080 cccatcctta cctggagcag tactacgacc cgagcgatga gcccgtcgcc gaagcaccct 1140 tcaagtttga catggaattg gatgacttgc ccaaggaaaa gctcaaagaa ctcatttttg 1200 aagagactgc tcgattccag ccgggatacc gatcttaaat ttgtcaggac acgggctcag 1260 agcacggcac gc 1272

<210> 16 <211> 2945 <212> ADN <213> Mus musculus <400> 16 tgccgctcgt gccgctttgg tggtggccgc ggttcttgtt aagtgagcga gcccggggga 60 acactcatca ctgggttggc aagactcagg aatcccaaat tcccgaggag gcgtggcggc 120 ggggtgccgg ccggtcggtc ctgcctccaa acccacagag gcggaactga gaggccctca 180 ggacgatctt ctcatcagcg cttcgtacag accatggccg aaccgctgaa ggaggaggac 240 ggcgaagatg gctctgggga gccccctggg agggtgaagg cagaacccgt tcacaccgct 300 gcctctgtgg tggccaagaa cctggccctg ctcaaagccc gctccttcga cgtgaccttt 360 gacgtggggg acgagtacga gatcatcgag accataggca atggggccta cggggtggtg 420 tcttcggcgc gccgccgcct cacgggccag caggtggcca tcaagaagat acctaatgct 480 tttgatgtgg tgaccaatgc caaacggacc ctcagggagc tgaagatcct caaacacttc 540 aaacacgaca atatcatcgc catcaaggac atcctgaagc ctactgtgcc ctatggagaa 600 ttcagatctg tctatgtggt actggacctc atggagagcg accfcacacca gatcattcac 660 tcttcacagc cgctcaccct ggaacatgtg agatacttcc tgtaccagct gcttcggggc 720 ctcaaataca tgcactotgc tcaggtcatc caccgtgatc ttaaacootc taaccttctg 780 gtcaatgaga actgtgagct caagatcggt gactttggaa tggcccgtgg cctctgtact 840 toocctgccg agcaccagta cttcatgact gagtatgtgg ctactogctg gtaccgtgcc 900 coggagctca tgctttocct gcacgagtat aogcaggcaa tcgacctctg gtctgtgggc 960 tgcatctttg gtgagatgct ggctcggcgc cagctcttcc caggcaaaaa ctacgtgcac 1020 cagttacagc tgatcatgat ggtgttggga actccgtcac cagctgtgat tcaggctgtg 1080 ggggctgaaa gggtgcgagc ctatatccag agcctgccac caaggcaacc tgtgccttgg 1140 gagacagtat acccaggtgc tgaccgccag gccctctccc tgctgggacg catgttgcga 1200 tttgaaccca gtgcccgaat ctcagctgct gctgcccttc gccacccctt cctggctaag 1260 taccatgacc ctgatgatga gcctgattgc gccccacctt ttgactttgc ttttgaccgt 1320 gaagccctta ccagggagcg cattaaggag gccattgtgg ctgagattga ggacttccat 1380 gcacgacggg agggcatccg ccaacaaatc cgcttccagc cttctctgca gcctgtggct 1440 agtgagcctg tgtgtccaga tgttgagatg cccagtccct gggctccaag tggagactgt 1500 gccatggagt cgcctcctcc agcactgcca ccatgctctg atectgcacc tgacaecgtt 1560 gatctgactc tgcagcctgc cccgccggcc agtgagcttg ctccaccaaa aagagagggt 1620 gccatctccg acaataccaa agcagccctc aaagctgccc tgctcaagtc cctaaggagc 1680 aggctcagag atgggcccag tgcacccttg gaggcgcctg agcctcgaaa gcccgtgaca 1740 gctcaggaac gccagcgaga acgagaagag aagcgcagga ggcgacaaga gagagccaag 1800 gagcgggaga agcgacgaca agagagagaa cgcaaggaga ggggggctgg taccttgggg 1860 ggcccctcta ctgaccctct ggctggactg gtgctcagtg acaatgaccg aagcctgcta 1920 gagcggtgga ctcgcatggc taggcctcct gcccctgccc ctgccccagc gccagcacca 1980 gcgccagcac cgtcctctgc ccagcccact agtactccta ctggccccgt atctcagtct 2040 actggtcctc tacagcctgc aggctctatt ccgggtcctg cctcccagcc tgtttgccca 2100 ccccctggcc ctgttcccca gcctgctggc cctatccctg ctccgctcca gactgcccct 2160 tccactagcc ttttggcctc ccagtcactt gtgccaccta gtgggttgcc tggttctggt 2220 gccccagaag ttctgcctta cttcccatct ggcccaccac ctccagatcc tgggctcacc 2280 cctcagcctt ctacatcaga gtcacctgat gtcaacctgg tgactcagca gctgtccaag 2340 tctcaggtgg aggaccccct gcctcctgtg ttctctggca ctccaaaggg cagtggggct 2400 ggctacggag ttggctttga tctggaggaa ttcttaaatc aatcttttga tatgggtgtg 2460 gctgatgggc cacaggatgg ccaggcagac tcagcctcac tctcagcctc tctccttgct 2520 gactggcttg agggccatgg catgaaccct gctgacattg agtctctgca gcgtgagatc 2580 cagatggact ccccaatgct gctgtctgac ctgcctgacc tccaagagcc ctgaaaccca 2640 cagcttgtgc cttgctgcca ggatagaccc agcatcaagg tccaggggtg cgatccaaag 2700 ggctgcaccc tgggcctggc aggtgaggct tggcttgagt tactctgcag gttcatctca 2760 gacccacctt tcagccttaa gcagccacct gagccaccac cgagccataa caggaccagg 2820 agactctaot cctccotgag cagtcttctc cagtattgta ttttttatta ttgttgtaat 2880 atgcatttgt tttgccatca aaatgaggcc tgtgaaatac aaggttttct ttaacctgaa 2940 aaaaa 2945

<210> 17 <211> 360 <212> PRT <213> Homo sapiens <400> 17

Met Ala Ala Ala Ala Ala Ala Gly Ala Gly Pro Glu Met Val Arg Gly 15 10 15

Gin Val Phe Asp Val Gly Pro Arg Tyr Thr Asn Leu Ser Tyr lie Gly 20 25 30

Glu Gly Ala Tyr Gly Met Val Cys Ser Ala Tyr Asp Asn Val Asn Lys 35 40 45

Val Arg Val Ala lie Lys Lys lie Ser Pro Phe Glu His Gin Thr Tyr 50 55 €0

Cys Gin Arg Thr Leu Arg Glu He Lys He Leu Leu Arg Phe Arg His 65 70 75 80

Glu Asn He He Gly He Asn Asp He He Arg Ala Pro Thr He Glu 85 90 95

Gin Met Lys Asp Val Tyr He Val Gin Asp Leu Met Glu Thr Asp Leu 100 105 110

Tyr Lys Leu Leu Lys Thr Gin His Leu Ser Asn Asp His He Cys Tyr 115 120 125

Phe Leu Tyr Gin He Leu Arg Gly Leu Lys Tyr lie His Ser Ala Asn 130 135 140

Val Leu His Arg Asp Leu Lys Pro Ser Asn Leu Leu Leu Asn Thr Thr 145 150 155 160

Cys Asp Leu Lys He Cys Asp Phe Gly Leu Ala Arg Val Ala Asp Pro 165 170 175

Asp His Asp His Thr Gly Phe Leu Thr Glu Tyr Val Ala Thr Arg Trp 180 185 190

Tyr Arg Ala Pro Glu He Met Leu Asn Ser Lys Gly Tyr Thr Lys Ser 195 200 205

He Asp He Trp Ser Val Gly Cys lie Leu Ala Glu Met Leu Ser Asn 210 215 220

Arg Pro He Phe Pro Gly Lys His Tyr Leu Asp Gin Leu Asn His lie 225 230 235 240

Leu Gly He Leu Gly Ser Pro Ser Gin Glu Asp Leu Asn Cys He He 245 250 255

Asn Leu Lys Ala Arg Asn Tyr Leu Leu Ser Leu Pro His Lys Asn Lys 260 265 270

Val Pro Trp Asn Arg Leu Phe Pro Asn Ala Asp Ser Lys Ala Leu Asp 275 280 285

Leu Leu Asp Lys Met. Leu Thr Phe Asn Pro His Lys Arg He Glu Val 290 295 300

Glu Gin Ala Leu Ala His Pro Tyr Leu Glu Gin Tyr Tyr Asp Pro Ser 305 310 315 320

Asp Glu Pro He Ala Glu Ala Pro Phe Lys Phe Asp Met Glu Leu Asp 325 330 335

Asp Leu Pro Lys Glu Lys Leu Lys Glu Leu He Phe Glu Glu Thr Ala 340 345 350

Arg Phe Gin Pro Gly Tyr Arg Ser 355 360

<210> 18 <211> 626 <212> PRT <213> Homo sapiens <4 0 0> 18

Met Asp Glu Gin Glu Ala Leu Asn Ser He Met Asn Asp Leu Val Ala 15 10 15

Leu Gin Met Asn Arg Arg His Arg Met Pro Gly Tyr Glu Thr Met Lys 20 25 30

Asn Lys Asp Thr Gly His Ser Asn Arg Gin Ser Asp Val Arg lie Lys 35 40 45

Phe Glu His Asn Gly Glu Arg Arg lie lie Ala Phe Ser Arg Pro Val 50 55 60

Lys Tyr Glu Asp Val Glu His Lys Val Thr Thr Val Phe Gly Gin Pro 65 70 75 80

Leu Asp Leu His Tyr Met Asn Asn Glu Leu Ser lie Leu Leu Lys Asn 85 90 95

Gin Asp Asp Leu Asp Lys Ala lie Asp He Leu Asp Arg Ser Ser Ser 100 105 110

Met Lys Ser Leu Arg lie Leu Leu Leu Ser Gin Asp Arg Asn His Asn 115 120 125

Ser Ser Ser Pro His Ser Glu Val Ser Arg Gin Val Arg lie Lys Ala 130 135 140

Ser Gin Ser Ala Gly Asp He Asn Thr He Tyr Gin Pro Pro Glu Pro 145 150 155 160

Arg Ser Arg His Leu Ser Val Ser Ser Gin Asn Pro Gly Arg Ser Ser 165 170 175

Pro Pro Pro Gly Tyr Val Pro Glu Arg Gin Gin His lie Ala Arg Gin 180 185 190

Gly Ser Tyr Thr Ser lie Asn Ser Glu Gly Glu Phe lie Pro Glu Thr 195 200 205

Ser Glu Gin Cys Met Leu Asp Pro Leu Ser Ser Ala Glu Asn Ser Leu 210 215 220

Ser Gly Ser Cys Gin Ser Leu Asp Arg Ser Ala Asp Ser Pro Ser Phe 225 230 235 240

Arg Lys Ser Arg Met Ser Arg Ala Gin Ser Phe Pro Asp Asn Arg Gin 245 250 255

Glu Tyr Ser Asp Arg Glu Thr Gin Leu Tyr Asp Lys Gly Val Lys Gly 260 265 270

Gly Thr Tyr Pro Arg Arg Tyr His Val Ser Val His His Lys Asp Tyr 275 280 285

Ser Asp Gly Arg Arg Thr Phe Pro Arg Ile Arg Arg His Gin Gly Asn 290 295 300

Leu Phe Thr Leu Vai Pro Ser Ser Arg Ser Leu Ser Thr Asn Gly Glu 305 310 315 320

Asn Met Gly Leu Ala Vai Gin Tyr Leu Asp Pro Arg Gly Arg Leu Arg 325 330 335

Ser Ala Asp Ser Glu Asn Ala Leu Ser Vai Gin Glu Arg Asn Vai Pro 340 345 350

Thr Lys Ser Pro Ser Ala Pro lie Asn Trp Arg Arg Gly Lys Leu Leu 355 360 365

Gly Gin Gly Ala Phe Gly Arg Vai Tyr Leu Cys Tyr Asp Vai Asp Thr 370 375 380

Gly Arg Glu Leu Ala Ser Lys Gin Vai Gin Phe Asp Pro Asp Ser Pro 385 390 395 400

Glu Thr Ser Lys Glu Vai Ser Ala Leu Glu Cys Glu Ile Gin Leu Leu 405 410 415

Lys Asn Leu Gin His Glu Arg Ile Vai Gin Tyr Tyr Gly Cys Leu Arg 420 425 430

Asp Arg Ala Glu Lys Thr Leu Thr lie Phe Met Glu Tyr Met Pro Gly 435 440 445

Gly Ser Vai Lys Asp Gin Leu Lys Ala Tyr Gly Ala Leu Thr Glu Ser 450 455 460

Vai Thr Arg Lys Tyr Thr Arg Gin lie Leu Glu Gly Met Ser Tyr Leu 465 470 475 480

His Ser Asn Met lie Vai His Arg Asp lie Lys Gly Ala Asn ile Leu 485 490 495

Arg Asp Ser Ala Gly Asn Vai Lys Leu Gly Asp Phe Gly Ala Ser Lys 500 505 510

Arg Leu Gin Thr lie Cys Met Ser Gly Thr Gly Met Arg Ser Vai Thr 515 520 525

Gly Thr Pro Tyr Trp Met Ser Pro Glu Vai Ile Ser Gly Glu Gly Tyr 530 535 540

Gly Arg Lys Ala Asp Val Trp Ser Leu Gly Cys Thr Val Val Glu Met 545 550 555 560

Leu Thr Glu Lys Pro Pro Trp Ala Glu Tyr Glu Ala Met Ala Ala lie 565 570 575

Phe Lys lie Ala Thr Gin Pro Thr Asn Pro Gin Leu Pro Ser His lie 580 585 590

Ser Glu His Gly Arg Asp Phe Leu Arg Arg lie Phe Val Glu Ala Arg 595 600 605

Gin Arg Pro Ser Ala Glu Glu Leu Leu Thr His His Phe Ala Gin Leu 610 615 620

Met Tyr 625

<210> 19 <211> 1064 <212> ADN <213> Homo sapiens <4 0 0> 19 atgtctcagg agaggcccac gttctaccgg caggagctga acaagacaat ctgggaggtg 60 cccgagcgtt accagaaoct gtctccagtg ggctctggcg cctatggctc tgtgtgtgct 120 gcttttgaca caaaaacggg gttacgtgtg gcagtgaaga agctctccag accatttcag 180 tccatcattc atgcgaaaag aacctacaga gaactgcggt tacttaaaca tatgaaacat 240 gaaaatgtga ttggtctgtt ggacgttttt acacctgcaa ggtctctgga ggaattcaat 300 gatgtgtatc tggtgaccca tctcatgggg gcagatctga acaacattgt gaaatgtcag 360 aagcttacag atgaccatgt tcagttcctt atctaccaaa ttctccgagg tctaaagtat 420 atacattcag ctgacataat tcacagggac ctaaaaccta gtaatctagc tgtgaatgaa 480 gactgtgagc tgaagattct ggattttgga ctggctcggc acacagatga tgaaatgaca 540 ggctacgtgg ccactaggtg gtacagggct cctgagatca tgctgaactg gatgcattac 600 aaccagacag ttgatatttg gtcagtggga tgcataatgg ccgagctgtt gactggaaga 660 acattgtttc ctgçrtacaga ccatattgat cagttgaagc tcattttaag actcgttgga 720 accccagggg ctgagctttt gaagaaaatc tcctcagagt ctctgtcgac ttgctggaga 780 agatgcttgt attggactca gataagagaa ttacagcggc ccaagccctt gcacatgcct 840 actttgctca gtaccacgat cctgatgatg aaccagtggc cgatccttat gatcagtcct 900 ttgaaagcag ggacctcctt atagatgagt ggaaaagcct gaoctatgat gaagtcatca 960 getttgtgcc accacccctt gaccaagaag agatggagtc ctgagcacct ggtttctgtt 1020 ctgttgatcc cacttcactg aggggaaggc cttttcacgg gaac 1064

<210> 20 <211> 3352 <212> ADN <213> Mus musculus <400> 20 aggaggaccg cggcgggagc agcctcgagc cgtgcagccg gctccggcac cttgccgacg 60 ctcgtaggag ccgccgcggc tgacaggggc ggcgggtcgc agcctccaca cctgcgcggg 120 tggcgggcgc ggggtccggt ctgccgcggg cgggcgcaga ggagagcgtg cggctgcagg 180 caggagcccc cgctcggcca cctcctcgcc ccgctgctgo cgctggaaga tgtcgcagga 240 gaggcccacg ttctaccggc aggagctgaa caagaccatc tgggaggtgc ccgaacgata 300 ccagaacctg tccccggtgg gctcgggcgo otatggotog gtgtgtgctg cttttgatac 360 aaagacgggg catcgtgtgg cagttaagaa gctgtcgaga ccgtttcagt ccatcattca 420 cgccaaaagg acctaccgag agttgcgtct gctgaagcac atgaaacacg aaaatgtgat 480 tggtctgttg gatgtgttca cacccgcaag gtcactggag gaattcaatg acgtgtacot 540 ggtgacccat ctcatggggg cggacctgaa caacatcgtg aagtgccaga agctgaccga 600 cgaccacgtt cagtttctca tctaccagat octccgaggg ctgaagtata tacattcggc 660 tgacataatt cacagggacc taaagcccag caacctagct gtgaacgaag actgtgagct 720 caagattctg gattttgggc tggctcggca cactgatgat gagatgacag gctacgtggc 780 taccaggtgg taccgagccc cagagatcat gctgaattgg atgcactata accagacagt 840 ggatatttgg tccgtgggct gcatcatggc tgagctgttg accggaagaa cgttgtttcc 900 tggtacagac catattaacc agcttcagca gataatgcgt atgacgggga caccccctgc 960 ttatctcatt aacaggatgc caagccatga ggcaagaaac tacattcagt ctctggccca 1020 gatgccgaag atgaacttcg caaatgtatt tattggtgcc aatcccctgg ctgtcgacct 1080 actggagaag atgctcgttt tggactcaga taagaggatc acagcagccc aagctcttgc 1140 gcatgcctac tttgctcagt accacgaccc tgatgatgag cctgttgctg acccttatga 1200 ccagtccttt gaaagcaggg accttctcat agatgagtgg aagagcctga cctatgatga 1260 agtcatcagc tttgtgccac caccccttga ccaagaagaa atggagtcct gagcacctgg 1320 tttctgttct gtctatctca cttcactgtg aggggaagac cttctcatgg gaactctcca 1380 aataccattc aagtgcctct tgttgaaaga ttccttcatg gtggaagggg gtgcatgtat 1440 gtgttagtgt ttgtgtgtgt gtgtgtgtct gtctgttcgt ctgtccacct atctttgtgg 1500 aagtcactgt gatggtagtg actttatgag ttgtgaafcgg tccttggcag tctgcctgct 1560 ttctcagagt ctgggcaggc cgatgggaac tgtcatctcc ttagggatgt gtgtgttcag 1620 tgcaaagtaa gaaatatgaa aatatccctg ttcttagtta ccttgccact ttggcttctc 1680 ctgtggccct gcctttacca tatcagtgac agagagaggc tgcttcaggt ctgaggctat 1740 ccctcagcca tgcataaagt ccaagagaac caactggctc ctggtctcta gcctgtgacc 1800 ggcttgctta atgtcctcag aacctgacag gtatgttcaa aactgtcagt ctgtttgtgc 1860 cttaaaaggg tgagaagggc gcgtagatag ttacagagtc tcagctgctg acgttctgag 1920 ccaggcaagb gcacggggct gttggatggc cagtggggag ctggaaaaaa caaggcagcc 1980 tttaggaagg ccatggtgca tgtgtgtgca tgcgtgtatg tgcagccgcc otccctcact 2040 tcaggagcaa gctgtttgct gtgcttaccc ttcacctcag tgcagaggtc tccagtgccg 2100 agcacaggca cctgccatca gtagttcctg tgtcatcttc acatctagca gagcacggat 2160 gtgtttgcat gctgtgctct tggagcttgt cctgtcttct ggaagccctg gacaaggcgt 2220 gtgaaggctt cccagaagtt cctgtccaca ttgcctccgc ccaccgacgc catgggcaca 2280 ctgctccctc ctcctcctcc agctactttg tgttgaacac aattgattct ccaggtgctc 2340 atggtgcagg aaaacaggac agacagagag cactgaaccc ttgccatctg atgtcaccaa 2400 ttcaggaaaa cgagtcctct cotaggacta tccccggttc tggaaatcat gttctcctca 2460 ctcatggtga caagctaaga aagctgaaca aagggagaga cgagagcgcc tgaagccagg 2520 agctccttta ctatctttct caaaagggtt gttagacaca aaccaagtca tcaaggcccc 2580 gctcctctcc tcggaagggt cccccacccc ccggcagctt gacactgaat ccagtgtcaa 2640 tttggggaga aagcagtttt gtcttggaat tttgtatgtt gtaggaatcc ttagagagtg 2700 tggttccttc tgatggggag aaagggcaaa ttattttaat attttgtatt ttcaccttta 2760 taaacatgaa tcctcagggg tgaagaactg tttgcataat tttctgaatt ttgagcactt 2820 tgtgctatat aaggacccat atttaagctt tgtgtgcagt aagaaagtgt aaagccaatt 2880 ccagtgttgg acgtgacagg tcttgtgttt aggtcaaggt gtctcctctc agtgcaggga 2940 catgcctgct ctgtggggca ggcgaggacc ctgaatcatt tggagcccag aaggaggcag 3000 actggccagg tctcaccacc tcagtgtgca gttcaactcc atgccatccc atcaagatgg 3060 gttagtagca gtgtctgttt ttgaatgcca agtgtgattt ccaacaattc tgctctggtt 3120 atttcattga agacatcttt gcacatgtga ccatgctgtg ttaggggctg tgttccaggg 3180 actggactcg aagctagaac tggcagaaga gttctggcat ccacagcgca atgctgccac 3240 cacccagttt cttcatcaga agacaaggga acgagaaaac tgctgttcgt ttgtatttgt 3300 gaacttggct gtaatctggt atgccatagg atgtcagata ataccactgg tt 3352

<210> 21 <211> 6641 <212> ADN <213> Homo sapiens <400> 21 gccctcgccg cccgcggcgc cccgagcgct ttgtgagcag atgcggagcc gagtggaggg 60 cgcgagccag atgcggggcg acagctgact tgctgagagg aggcggggag gcgcggagcg 120 cgcgtgtggt ccttgcgccg ctgacttctc cactggttcc tgggcaccga aagataaacc 180 tctcataatg aaggcccccg ctgtgcttgc acctggcatc ctcgtgctcc tgtttacctt 240 ggtgcagagg agcaatgggg agtgtaaaga ggcactagca aagtccgaga tgaatgtgaa 300 tatgaagtat cagcttccca acttcaccgc ggaaacaccc atccagaatg tcattctaca 360 tgagcatcac attttccttg gtgccactaa ctacatttat gttttaaatg aggaagacct 420 tcagaaggtt gctgagtaca agactgggcc tgtgctggaa cacccagatt gtttcccatg 480 tcaggactgc agcagcaaag ccaatttatc aggaggtgtt tggaaagata acatcaacat 540 ggctctagtt gtcgacacct actatgatga tcaactcatt agctgtggca gcgtcaacag 600 agggacctgc cagcgacatg tctttcccca caatcatact gctgacatac agtcggaggt 660 tcactgcata ttctccccac agatagaaga gcccagccag tgtcctgact gtgtggtgag 720 cgccctggga gccaaagtcc tttcatctgt aaaggaccgg ttcatcaact tctttgtagg 780 caataccata aattcttctt atttcccaga tcatccattg cattcgatat cagtgagaag 840 gctaaaggaa acgaaagatg gttttatgtt tttgacggac cagtcctaca ttgatgtttt 900 acctgagttc agagattctt accccattaa gtatgtccat gcctttgaaa gcaacaattt 960 tatttacttc ttgacggtcc aaagggaaac tctagatgct cagacttttc acacaagaat 1020 aatcaggttc tgttccataa actctggatt gcattcctac atggaaatgc ctctggagtg 1080 tattctcaca gaaaagagaa aaaagagatc cacaaagaag gaagtgttta atatacttca 1140 ggctgcgtat gtcagcaagc ctggggccca gcttgctaga caaataggag ccagcctgaa 1200 tgatgacatt ottttcgggg tgttcgcaca aagcaagcca gattctgccg aaccaatgga 1260 tcgatctgcc atgtgtgcat tccctatcaa atatgtcaac gacttcttca acaagatcgt 1320 caacaaaaac aatgtgagat gtctccagca tttttacgga cccaatcatg agcactgctt 1380 taataggaca cttctgagaa attcatcagg ctgtgaagcg cgccgtgatg aatatcgaac 1440 agagtttacc acagctttgc agcgcgttga cttattcatg ggtcaattca gcgaagtcct 1500 cttaacatct atatccacct tcattaaagg agacctcacc atagctaatc ttgggacatc 1560 agagggtcgc ttcatgcagg ttgtggtttc tcgabcagga ccatcaaccc ctcatgtgaa 1620 ttttctcctg gactcccatc cagtgtctcc agaagtgatt gtggagcata cattaaacca 1680 aaatggctac acactggtta tcactgggaa gaagatcacg aagatcccat tgaatggctt 1740 gggctgcaga catttccagt cctgcagtca atgcctctct gccccaccct ttgttcagtg 1800 tggctggtgc cacgacaaat gtgtgcgatc ggaggaatgc ctgagcggga catggactca 1860 acagatctgt ctgcctgcaa tctacaaggt tttcccaaat agtgcacccc ttgaaggagg 1920 gacaaggctg accatatgtg gctgggactt tggatttcgg aggaataata aatttgattt 1980 aaagaaaact agagttctcc ttggaaatga gagctgcacc ttgactttaa gtgagagcac 2040 gatgaataca ttgaaatgca cagttggtcc tgccatgaat aagcatttca atatgtccat 2100 aattatttca aatggccacg ggacaacaca atacagtaca ttctcctatg tggatcctgfc 2160 aataacaagt atttcgccga aatacggtcc tatggctggt ggcactttac ttactttaac 2220 tggaaattac ctaaacagtg ggaattctag acacatttca attggtggaa aaacatgtac 2280 tttaaaaagt gtgtcaaaca gtattcttga atgttatacc ccagcccaaa ccatttcaac 2340 tgagtttgct gttaaattga aaattgactt agccaaccga gagacaagca tcttcagtta 2400 ccgbgaagat cccattgtct atgaaattca tccaaccaaa tcttttatta gtggbgggag 2460 cacaataaca ggtgttggga aaaacctgaa ttcagttagt gtcccgagaa tggtcataaa 2520 tgtgcatgaa gcaggaagga actttacagt ggcatgtcaa catcgctcta attcagagat 2580 aatctgttgt accactcctt ccctgcaaca gctgaatctg caactccccc tgaaaaccaa 2640 agcctttttc atgttagatg ggatcctttc caaatacttt gatctcattt atgtacataa 2700 fccctgtgbtt aagccttttg aaaagccagt gatgatctca atgggcaatg aaaatgtact 2760 ggaaattaag ggaaatgata ttgaccctga agcagttaaa ggtgaagtgt taaaagttgg 2820 aaataagagc tgtgagaata tacacttaca ttctgaagcc gttttatgca cggtccccaa 2880 tgacctgctg aaattgaaca gcgagctaaa tatagagtgg aagcaagcaa tttcttcaac 2940 cgtccttgga aaagtaatag ttcaaccaga tcagaatttc acaggattga ttgctggtgt 3000 tgtctcaata tcaacagcac tgttattact acttgggttt ttcctgtggc tgaaaaagag 3060 aaagcaaatt aaagatctgg gcagtgaatt agttcgctac gatgcaagag tacacactcc 3120 tcatttggat aggcttgtaa gtgcccgaag tgtaagccca actacagaaa tggtttcaaa 3180 tgaatctgta gactaccgag ctacttttcc agaagatcag tttcctaatt catctcagaa 3240 cggttcatgc cgacaagtgc agtatcctct gacagacatg tcccccatcc taactagtgg 3300 ggactctgat atatccagtc cattactgca aaatactgtc cacattgacc tcagtgctct 3360 aaatccagag ctggtccagg cagtgcagca tgtagtgatt gggcccagta gcctgattgt 3420 goatttcaat gaagtcatag gaagagggca ttttggttgt gtatatcatg ggactttgtt 3480 ggacaatgafc ggcaagaaaa ttcactgtgc tgtgaaatcc ttgaacagaa tcactgacat 3540 aggagaagtt tcccaatttc tgaccgaggg aatcatcatg aaagatttta gtcatcccaa 3600 tgtcctctcg ctcctgggaa tctgcctgcg aagtgaaggg tctccgctgg tggtcctacc 3660 atacatgaaa catggagatc ttcgaaattt cattcgaaat gagactcata atccaactgt 3720 aaaagatctt attggctttg gtcttcaagt agccaaaggc atgaaatatc ttgcaagcaa 3780 aaagtttgtc cacagagact tggctgcaag aaactgtatg ctggatgaaa aattcacagt 3840 caaggttgct gattttggtc ttgccagaga catgtatgat aaagaatact atagtgtaca 3900 caacaaaaca ggtgcaaagc tgccagtgaa gtggatggct ttggaaagtc tgcaaactca 3960 aaagtttacc accaagtcag atgtgtggtc ctttggcgtg ctcctctggg agctgatgac 4020 aagaggagcc ccaccttatc ctgacgtaaa cacctttgat ataactgttt acttgttgca 4080 agggagaaga ctcctacaac ccgaatactg cccagacccc ttatatgaag taatgctaaa 4140 atgctggcac cctaaagccg aaatgcgccc atccttttct gaactggtgt cccggatatc 4200 agcgatcttc tctactttca ttggggagca ctatgtccat gtgaacgcta cttatgtgaa 4260 cgtaaaatgt gtcgctccgt atccttctct gttgtcatca gaagataacg ctgatgatga 4320 ggtggacaca cgaccagcct ccttctggga gacatcatag tgctagtact atgtcaaagc 4380 aacagtccac actttgtcca atggtttttt cactgcctga cctttaaaag gccatcgata 4440 ttctttgctc ttgccaaaat tgcactatta taggacttgt attgttattt aaattactgg 4500 attctaagga atttcttatc tgacagagca tcagaaccag aggcttggtc ccacaggcca 4560 cggaccaatg gcctgcagcc gtgacaacac tcctgtcata ttggagtcca aaacttgaat 4620 tctgggttga attttttaaa aatcaggtac cacttgattt catatgggaa attgaagcag 4680 gaaatattga gggcttcttg atcacagaaa actcagaaga gatagtaatg ctcaggacag 4740 gagcggcagc cccagaacag gccactcatt tagaattcta gtgtttcaaa acacttttgt 4800 gtgttgtatg gtcaataaca tttttcatta ctgatggtgt cattcaccca ttaggtaaac 4860 attccctttt aaatgtttgt ttgttttttg agacaggatc tcactctgtt gccagggctg 4920 tagtgcagtg gtgtgatcat agctcactgc aacctccacc tcccaggctc aagcctcccg 4980 aat.agct.ggg actacaggcg cacaccacca tccccggcta atttttgtat tttttgtaga 5040 gacggggttt tgccatgttg ccaaggctgg tttcaaactc ctggactcaa gaaatccacc 5100 cacctcagcc tcccaaagtg ctaggattac aggcatgagc cactgcgccc agcccttata 5160 aatttttgta tagacattcc tttggttgga agaatattta taggcaatac agtcaaagtt 5220 tcaaaatagc atcacacaaa acatgtttat aaatgaacag gatgtaatgt acatagatga 5280 cattaagaaa atttgtatga aataatttag tcatcatgaa atatttagtt gtcatataaa 5340 aacccactgt ttgagaatga tgctactctg atctaatgaa tgtgaacatg tagatgtttt 5400 gtgtgtattt ttttaaatga aaactcaaaa taagacaagt aatttgttga taaatatttt 5460 taaagataac tcagcatgtt tgtaaagcag gatacatttt actaaaaggt tcattggttc 5520 caatcacagc tcataggtag agcaaagaaa gggtggatgg attgaaaaga ttagcctctg 5580 tctcggtggc aggttcccac ctcgcaagca attggaaaca aaacttttgg ggagttttat 5640 tttgcattag ggtgtgtttt atgttaagca aaacatactt tagaaacaaa tgaaaaaggc 5700 aattgaaaat cccagctatt tcacctagat ggaatagcca ccctgagcag aactttgtga 5760 tgcttcattc tgtggaattt tgtgcttgct actgtatagt gcatgtggtg taggttactc 5820 taactggttt tgtcgacgta aacatttaaa gtgttatatt ttttataaaa atgtttattt 5880 ttaatgatat gagaaaaatt ttgttaggcc acaaaaacac tgcactgtga acattttaga 5940 aaaggtatgt cagactggga ttaatgacag catgattttc aatgactgta aattgcgata 6000 aggaaatgta ctgattgcca atacacccca ccctcattac atcatcagga cttgaagcca 6060 agggttaacc cagcaagcta caaagagggt gtgtcacact gaaactcaat agttgagttt 6120 ggctgttgtt gcaggaaaat gattataact aaaagctctc tgatagtgca gagacttacc 6180 agaagacaca aggaattgta ctgaagagct attacaatcc aaatattgcc gtttcataaa 6240 tgtaataagt aatactaatt cacagagtat tgtaaatggt ggatgacaaa agaaaatctg 6300 ctctgtggaa agaaagaact gtctctacca gggtcaagag catgaacgca tcaatagaaa 6360 gaactcgggg aaacatccca tcaacaggac tacacacttg tatatacatt cttgagaaca 6420 ctgcaatgtg aaaatcacgt ttgctattta taaacttgtc cttagattaa tgtgtctgga 6480 cagattgtgg gagtaagtga ttcttctaag aattagatac ttgtcactgc ctatacctgc 6540 agctgaactg aatggtactt cgtatgttaa tagttgttct gataaatcat gcaattaaag 6600 taaagtgatg caacatcttg taaaaaaaaa aaaaaaaaaa a 6641 <210> 22 <211> 3843 <212> ADN <213> Danio rerio <400> 22 atggggggtg cgcgcogaat atgtgcggac gctcccgaca ccgctggctg ggcagatgag 60 cggtaccaaa cgcgcaccag tctgccatta cacaaaggat tcccacggca atccgatgga 120 ctctgcacag aaaggggtcg actaattaca gtcttactcg acacccccgg attcaccaag 180 gataactggc ttgagaggga tgacacgact gagcacaatc tacgtgacat gggattcctg 240 aagacacatc tcgtttttgg gattgtctta ctaggggtgt tttcagatgt ctcgaagcca 300 tggctagtta cggataaaga gaaagaggaa ttcatgctga caccacattc cgactttaac 360 atcacttgct ttggaatgag gagagtaact tgggtcgaac cattaccgtt caacatcaaa 420 gttcattctg gatttaacta cagtacttta atgatcactg atgcggtggc ctctaacact 480 cgtttctaca cctgccagca tgaggatcat tctgaaactg aaactgatat ctacattttt 540 gttcaagatc ccgatgttcc atttgtgtct gaacacgatg ctgagacaga tgaaataggc 600 acaacaatcc cctgccacgt aacaaaccca cattctgaag tgatgctcag agatctgcag 660 agcggggatg aggttactgt gctttatgac cccaaacttg gcttttttgg tacaataccg 720 ccaggacaat acgtctgtga gacaactgtg aatggcaaaa cagtgcggag catcgtttat 780 aatgtgacaa atgacatggc tactgacgtt cctgaggttg tagaccagaa cttcagcatc 840 cagctgagcg ccagtatgga ggatttgaaa gagggagatt cagtcaacct cacctgtgag 900 actcctgctg gaatggcttt ccaccagcag tggctgcatc cccaaaaaca ggccaaagac 960 ggggtcccaa taaagttaac tctccaagat aagatccagt acatcctcaa catcccaaaa 1020 gcttctgtgg aagacaccgg acgctatgag tgttctgtga caaaccagct tactagacaa 1080 accaggtcca aaagcctggg catcacagtt cacgagagct catttgtgga aattatatct 1140 aatggtattg ggccagtgga ggttgtgtct cttctggagg aaaaagagtt cactatttac 1200 attgatgctg accctgagcc aaaggtcaca tggtttaaag atggacagcc attggaggac 1260 agctacatct tctctaagac cactcatcta gaaaacctca ggtatgaaaa tattctgatt 1320 ctccgacacc ctgtagaaga agacagcggc atttatgaga tcgttgcttc caccggctcc 1380 aggacttcac aattttcatt caaaotcctc attgaagtca tgttcccggt gctgccacag 1440 tcagttcagg ctccactgat ttggccccag agggagagta tggaggtgtc tctgcactcc 1500 actttcagac tcacatgtcg aggtcaagcc gagctctcct ggaatggccc tgtttttatt 1560 gatgaccaga ccaacagtgt aaagaaagga ctctttatta gcactgtgac aattagcaat 1620 gccacagctg tccatacagg agagtacgtc tgctcttctg aacccttcaa cagcactgag 1680 tcaaccatct atatttatgt gccagatcca caaaccccat ttgtgccgtc catgaccccg 1740 tttgaaaacc acgtgctgac gagttatgat gaaatggaga ttccctgccg tgtgacggat 1800 cccagtgcca gcgtctctct catccacatg gagaccgatc aagttatgcc cagcgcctac 1860 gacagcaaga gaggattcat cgggctcttc ggcgctggga cgtatgtctg ccgagccctc 1920 attcatggac agaatcatga cagcattgag tacattgttc atggatggac aggagggtct 1980 gatttgcgag tggagctgcg ggcagtgaag agaactctgc tggtgggtga gactatcact 2040 gttgactgtg tagccaaagg cagtgagatg ctggaggacc actggaaata ccctggcaaa 2100 ctggctaatc gtggaacaaa gactgtaaag gagaataagc taaatctgga gatctattat 2160 actctgacag tgactaatgc ctcaccaaaa gacagcggca tctatgcctg ctccatcact 2220 gacatcatga gcaacgagag ccaaaccaaa gagctgacta ttactgtcta tgatcatgaa 2280 tttgtccaca tcaatccatt gatcggtcca gtggaaactg ccaggctgga cgaggtgcca 2340 gagtttaaag tggacataga gtctttccct gcacccaaag ttacatggtt aaaggacagc 2400 gctgtcctgg gagatgatac tgcagagatc agcaccaacc tcctcaaaat cggcgagacc 2460 agttacaagg gtgtgttgaa cctgatcaga gctaaagcag aggacagtgg aaactacacc 2520 gtcaaggcag aaataggcag cataagtacc agctacagtt tctaccttca ggttaaagtt 2580 ccccctgtga ttgtggacct gatggacgtc catcatggtt cfcgctgcggg tcaggaagtg 2640 gbatgcactg ctggcggctc cccattccct gaagtggact ggtatatctg caaaaacctt 2700 aaacactgtg ccaatgattc ctcccagtgg atgccacttc cgatcaactc gacggacatc 2760 acagtggaac tgcaaatgaa tgtggacaac cacattgaga gccacattat tttccaccat 2820 cttgagggca cagtcgctgt gcgctgtctg gccaggaatg acatgggtgt tgtttcacgg 2880 gaggttaaac tcatgtcaag tggtccgcat tcggagctca ctgtggctgc tgcggttctg 2940 gtgctgctgg tcattgtcat catctcactc attgtgctgg tcattatatg gaaacagaaa 3000 ccacgttatg agattagatg gcgcgtgatt gaatcagtca gtccggatgg gcacgagtac 3060 atctatgbcg atcccatgca gcttccatat gattcccgct gggacpttccc tcgggatgga 3120 ctcgttctgg gtcgcgtcct gggttcagga gcttttggta aagtggtgga gggtactgct 3180 tatggactaa gccgttctca gcctgtgatg aaagttgctg tgaaaatgct taagccgacc 3240 gcccgttcca gtgagaaaca agctttgatg tcagagctga aaatcatgac ccatctgggc 3300 cctcacctaa acattgttaa ccttctggga gcgbgtacca aatcaggacc aatctacatt 3360 ataacagagt attgtttcta tggagatctg gtgaattacc ttcataagaa cagagatggg 3420 tttctcagcc ggcacacaga aaagggaaag aaagatctag acatctttgg catcaaccca 3480 gccgatgaga gcagcaggag ctatgtcatc ctgtctttcg aggggaaagg tgattatatg 3540 gacatgaagc aggcagacac catgcagtac gtccccatgc tggaaatgaa tgaagcctca 3600 aaatactctc ccatccagag atcagactac gaccatcctc cctctcacag acaattcaat 3660 ggagaagctg taaggggcca gtgcattgtg gaattaggtg gtggtcgaag ctgtgatgca 3720 acacctgtgg tgccttttgt ggacacaaac ccggtggtgg acaccgatag taagggatgc 3780 tgtcaagctg aaggaggagt cttaccaggc ttgattggct tgtgggactc cagaggcatc 3840 tga 3843

<210> 23 <211> 5718 <212> ADN <213> Homo sapiens <400> 23 ctcctgaggc tgccagcagc cagcagtgac tgcccgccct atctgggacc caggatcgct 60 ctgtgagcaa cttggagcca gagaggagat caacaaggag gaggagagag ccggcccctc 120 agccctgctg cccagcagca gcctgtgctc gccctgccca acgcagacag ccagacccag 180 ggcggcccct ctggcggctc tgctcctccc gaaggatgct tggggagtga ggcgaagctg 240 ggccgctcct otcoootaca gcagccccct tcctccatcc ctctgttctc ctgagccttc 300 aggagcctgc accagtcctg cctgtccttc tactcagctg ttacccactc tgggaccagc 360 agtctttctg ataactggga gagggcagta aggaggactt cctggagggg gtgactgtcc 420 agagcctgga actgtgccca caccagaagc catcagcagc aaggacacca tgcggcttcc 480 gggtgcgatg ccagctctgg ccctcaaagg cgagctgctg ttgctgtctc tcctgttact 540 tctggaacca cagatctctc agggcctggt cgtcacaccc ccggggccag agcttgtcct 600 caatgtctcc agcaccttcg ttctgacctg ctcgggttca gctccggtgg tgtgggaacg 660 gatgtcccag gagcccccac aggaaatggc caaggcccag gatggcacct tctccagcgt 720 gctcacactg accaacctca ctgggctaga cacgggagaa tacttttgca cccacaatga 780 ctcccgtgga ctggagaccg atgagcggaa acggctctac atctttgtgc cagatcccac 840 cgtgggcttc ctccctaatg atgccgagga actattcatc tttctcacgg aaataactga 900 gatcaccatt ccatgccgag taacagaccc acagctggtg gtgacactgc acgagaagaa 960 aggggacgtt gcactgcctg tcccctatga tcaecaacgt ggcttttctg gtatctttga 1020 ggacagaagc tacatctgca aaaccaccat tggggacagg gaggtggatt ctgatgccta 1080 ctatgtctac agactccagg tgtcatccat caacgtctct gtgaacgcag tgcagactgt 1140 ggtccgccag ggtgagaaca tcaccctcat gtgcattgtg atcgggaatg aggtggtcaa 1200 cttcgagtgg acataccccc gcaaagaaag tgggcggctg gtggagccgg tgactgactt 1260 cctcttggat atgccttacc acatccgctc catcctgcac atccccagtg ccgagttaga 1320 agactcgggg acctacacct gcaatgtgac ggagagtgtg aatgaccatc aggatgaaaa 1380 ggccatcaac atcaccgtgg ttgagagcgg ctacgtgcgg ctcctgggag aggtgggcac 1440 actacaattt gctgagctgc atcggagccg gacactgcag gtagtgttcg aggcctaccc 1500 accgcccact gtccfcgtggt tcaaagacaa ccgcaccctg ggcgactcca gcgctggcga 1560 aatcgccctg tccacgcgca acgtgtcgga gacccggtat gtgtcagagc tgacactggt 1620 tcgcgtgaag gtggcagagg ctggccacta caccatgcgg gccttccatg aggatgctga 1680 ggtccagctc tccttccagc tacagatcaa tgtccctgtc cgagtgctgg agctaagtga 1740 gagccaccct gacagtgggg aacagacagt ccgctgtcgt ggccggggca tgccccagcc 1800 gaacatcatc tggtctgcct gcagagacct caaaaggtgt ccacgtgagc tgccgcccac 1860 gctgctgggg aacagttccg aagaggagag ccagctggag actaacgtga cgtactggga 1920 ggaggagcag gagtttgagg tggtgagcac actgcgtctg cagcacgtgg atcggccact 1980 gtcggtgcgc tgcacgctgc gcaacgctçrt gggccaggac acgcaggagg tcatcgtggt 2040 gccacactcc ttgcccttta aggtggtggt gatctcagcc atcctggccc tggtggtgct 2100 caccatcatc tcccttatca tcctcatcat gctttggcag aagaagccac gttacgagat 2160 ccgatggaag gtgattgagt ctgtgagctc tgacggccat gagtacatct acgtggaccc 2220 catgcagctg ccctatgact ccacgtggga gctgccgcgg gaocagcttg tgctgggacg 2280 caccctcggc tctggggcct ttgggcaggt ggtggaggco acggctcatg gcctgagcca 2340 ttctcaggcc acgatgaaag tggccgtcaa gatgcttaaa tccacagccc gcagcagtga 2400 gaagcaagcc cttatgtcgg agctgaagat catgagtcac cttgggcccc acctgaacgt 2460 ggtcaacctg ttgggggcct gcaccaaagg aggacccatc tatatcatca ctgagtactg 2520 ccgctacgga gacctggtgg actacctgca ccgcaacaaa cacaccttcc tgcagcacca 2580 ctccgacaag cgccgcccgc ccagcgcgga gctctacagc aatgctctgc ccgttgggct 2640 ccccctgccc agccatgtgt ccttgaocgg ggagagogao ggtggctaca tggacatgag 2700 caaggacgag tcggtggact atgtgcccat gctggacatg aaaggagacg tcaaatatgc 2760 agacatcgag tcctccaact acatggcccc ttacgataac tacgttccct ctgcccctga 2820 gaggacctgc cgagcaactt tgatcaacga gtctccagtg ctaagctaca tggacctcgt 2880 gggcttcagc tacoaggtgg ccaatggcat ggagtttctg gcctccaaga actgogtcca 2940 cagagacctg gcggctagga acgtgctcat ctgtgaaggc aagctggtca agatctgtga 3000 ctttggcctg gctcgagaca tcatgcggga ctcgaattac atctccaaag gcagcacctt 3060 tttgccttta aagtggatgg ctccggagag catcttcaac agcctctaca ccaccctgag 3120 cgacgtgtgg tcottcggga tcctgctctg ggagatotto accttgggtg gcacccctta 3180 cccagagctg cccatgaacg agcagttcta caatgccatc aaacggggtt accgcatggc 3240 ccagcctgcc catgcctccg acgagatcta tgagatcatg cagaagtgct gggaagagaa 3300 gtttgagatt cggcccccct tctcccagct ggtgctgctt ctcgagagac tgttgggcga 3360 aggttacaaa aagaagtacc agcaggtgga tgaggagttt ctgaggagtg accacccagc 3420 catccttcgg tcccaggccc gcttgcctgg gttccatggc ctccgatctc ccctggacac 3480 cagctccgtc ctctatactg ccgtgcagcc caatgagggt gacaacgact atatcatccc 3540 cctgcctgac cccaaacccg aggttgctga cgagggccca ctggagggtt cccccagcct 3600 agccagctcc accctgaatg aagtcaacac ctcctcaacc atctcctgtg acagccccct 3660 ggagccccag gacgaaccag agccagagcc ccagcttgag ctccaggtgg agccggagcc 3720 agagctggaa cagttgccgg attcggggtg ccctgcgcct cgggcggaag cagaggatag 3780 cttcctgtag ggggctggcc cctaccctgc cctgcctgaa gctccccccc tgccagcacc 3840 cagcatctcc tggcctggcc tgaccgggct tcctgtcagc caggctgccc ttatcagctg 3900 tccccttctg gaagctttct gctcctgacg tgttgtgccc caaaccctgg ggctggctta 3960 ggaggcaaga aaactgcagg ggccgtgacc agccctctgc ctccagggag gccaactgac 4020 tctgagccag ggttccccca gggaactcag ttttcccata tgtaagatgg gaaagttagg 4080 cttgatgacc cagaatctag gattctctcc ctggctgaca ggtggggaga ccgaatccct 4140 ccctgggaag attcttggag ttactgaggt ggtaaattaa cttttttctg ttcagccagc 4200 tacccctcaa ggaatcatag ctctctcctc gcacttttat ccacccagga gctagggaag 4260 agaccctagc ctccctggct gctggctgag ctagggccta gccttgagca gtgttgcctc 4320 atccagaaga aagccagtct cctccctatg atgccagtcc ctgcgttccc tggcccgagc 4380 tggtctgggg ccattaggca gcctaattaa tgctggaggc tgagccaagt acaggacacc 4440 cccagcctgc agcccttgcc cagggcactt ggagcacacg cagccatagc aagtgcctgt 4500 gtccctgtcc ttcaggccca tcagtcctgg ggctttttct ttatcaccct cagtcttaat 4560 ccatccacca gagtctagaa ggccagacgg gccccgcatc tgtgatgaga atgtaaatgt 4620 gccagtgtgg agtggccacg tgtgtgtgcc agtatatggc cctggctctg cattggacot 4680 gctatgaggc tttggaggaa tccctcaccc tctctgggcc tcagtttccc cttcaaaaaa 4740 tgaataagtc ggacttatta actctgagtg ccttgccagc actaacattc tagagtattc 4800 caggtggttg cacatttgtc cagatgaagc aaggccatat accctaaact tccatcctgg 4860 gggtcagctg ggctcctggg agattccaga tcacacatca cactctgggg actcaggaac 4920 catgcccctt ccccaggccc ccagcaagtc tcaagaacac agctgcacag gccttgactt 4980 agagtgacag ccggtgtcct ggaaagcccc cagcagctgc cccagggaca tgggaagacc 5040 acgggacctc tttcactacc cacgatgacc tccgggggta tcctgggcaa aagggacaaa 5100 gagggcaaat gagatcacct cctgcagccc accactccag cacctgtgcc gaggtctgcg 5160 tcgaagacag aatggacagt gaggacagtt atgtcttgta aaagacaaga agcttcagat 5220 gggtacccca agaaggatgt gagaggtggg cgctttggag gtttgcccct cacccaccag 5280 ctgccccatc cctgaggcag cgctccatgg gggtatggtt ttgtcactgc ccagacctag 5340 cagtgacatc tcattgtccc cagcccagtg ggcattggag gtgccagggg agtcagggtt 5400 gtagccaaga cgcccccgca cggggagggt tgggaagggg gtgcaggaag ctcaacccct 5460 ctgggcacca accctgcatt gcaggttggc accttacttc cctgggatcc ccagagttgg 5520 tccaaggagg gagagtgggt tctcaatacg gtaccaaaga tataatcacc taggtttaca 5580 aatattfctta ggactcacgt taactcacat ttatacagca gaaatgctat tttgtatgct 5640 gttaagtttt tctatctgtg tacttttttt taagggaaag attttaatat taaacotggt 5700 gcttctcact cacaaaaa 5718

<210> 24 <211> 1883 <212> ADN <213> Homo sapiens <400> 24 cccgcccccg cgccgggccc ggctcggccc gacccggctc cgccgcgggc aggcggggcc 60 cagcgcactc ggagcccgag cccgagccgc agccgccgcc tggggcgctt gggtcggcct 120 cgaggacacc ggagaggggc gccacgccgc cgtggccgca gatttgaaag aagccaacac 180 taaaccacaa atatacaaca aggccatttt ctcaaacgag agtcagcctt taacgaaatg 240 accatggttg acacagagat gccattctgg cccaccaact ttgggatcag ctccgtggat 300 ctctccgtaa tggaagacca ctcccactcc tttgatatca agcccttcac tactgttgac 360 ttctccagca tttctactcc acattacgaa gacattccat tcacaagaac agatccagtg 420 gttgcagatt acaagtatga cctgaaactt caagagtacc aaagtgcaat caaagtggag 480 cctgcatctc caccttatta ttctgagaag actcagctct acaataagcc tcatgaagag 540 ccttccaact ccctcatggc aattgaatgt cgtgtctgtg gagataaagc ttctggattt 600 cactatggag ttcatgcttg tgaaggatgc aagggtttct tccggagaac aatcagattg 660 aagcttatct atgacagatg tgatcttaac tgtcggatcc acaaaaaaag tagaaataaa 720 tgtcagtact gtcggtttca gaaatgcctt gcagtgggga tgtctcataa tgccatcagg 780 tttgggcgga tgccacaggc cgagaaggag aagctgttgg cggagatctc cagtgatatc 840 gaccagctga atccagagtc cgctgacctc cgggccctgg caaaacattt gtatgactca 900 tacataaagt ccttcccgct gaccaaagca aaggcgaggg cgatcttgac aggaaagaca 960 acagacaaat caccattcgt tatotatgac atgaattcct taatgatggg agaagataaa 1020 atcaagttca aacacatcac ccccctgcag gagcagagca aagaggtggc catccgcatc 1080 tttcagggct gccagtttcg ctccgtggag gctgtgcagg agatcacaga gtatgccaaa 1140 agcattcctg gttttgtaaa tcttgacttg aacgaccaag taactctcct caaatatgga 1200 gtccacgaga tcatttacac aatgctggcc tccttgatga ataaagatgg ggttctcata 1260 tccgagggcc aaggcttcat gacaagggag tttctaaaga gcctgcgaaa gccttttggt 1320 gactttatgg agcccaagtt tgagtttgct gtgaagttca atgcactgga attagatgac 1380 agcgacttgg caatatttat tgctgtcatt attctcagtg gagaccgccc aggtttgctg 1440 aatgtgaagc ccattgaaga cattcaagac aacctgctac aagccctgga gctccagctg 1500 aagctgaacc accctgagtc ctcacagctg tttgccaagc tgctccagaa aatgacagac 1560 ctcagacaga ttgtcacgga acacgtgcag ctactgcagg tgatcaagaa gacggagaca 1620 gacatgagtc ttcacccgct cctgcaggag atctacaagg acttgtacta gcagagagtc 1680 ctgagccact gccaacattt cccttcttcc agttgcacta ttctgaggga aaatctgaca 1740 cctaagaaat ttactgtgaa aaagcatttt aaaaagaaaa ggttttagaa tatgatctat 1800 tttatgcata ttgtttataa agacacattt acaatttact tttaatatta aaaattacca i860 tattatgaaa aaaaaaaaaa aaa 1883

<210> 25 <211> 5449 <212> ADN <213> Homo sapiens <400> 25 gcgccggggg ccgccgcgcc cgccgcccgc tgcctgcgcc gccggccggg catgagttag €0 tcgcagacat ggacaccaaa catttcctgc cgctcgattt ctccacccag gtgaactcct 120 ccctcacctc cccgacgggg cgaggctcca tggctgcccc ctcgctgcac ccgtccctgg 180 ggcctggcat cggctccccg ggacagctgc attctcccat cagcaccctg agctccccca 240 tcaacggcat gggcccgcct ttctcggtca tcagctcccc catgggcccc cactccatgt 300 cggtgcccac cacacccacc ctgggcttca gcactggcag cccccagctc agctcaccta 360 tgaaccccgt cagcagcagc gaggacatca agccccccct gggcctcaat ggcgtcctca 420 aggtccccgc ccacccctca ggaaacatgg cttccttcac caagcacatc tgcgccatct 480 gcggggaccg ctcctcaggc aagcactatg gagtgtacag ctgcgagggg tgcaagggct 540 tcttcaagcg gacggtgcgc aaggacctga cctacacctg ccgcgacaac aaggactgcc 600 tgattgacaa gcggcagcgg aaccggtgcc agtactgccg ctaccagaag tgcctggcca 660 tgggcatgaa gcgggaagcc gtgcaggagg agcggcagcg tggcaaggac cggaacgaga 720 atgaggtgga gtcgaccagc agcgccaacg aggacatgcc ggtggagagg atcctggagg 780 ctgagctggc cgtggagccc aagaccgaga cctacgtgga ggcaaacatg gggctgaacc 840 ccagctcgcc gaacgaccct gtcaccaaca tttgccaagc agccgacaaa cagcttttca 900 ccctggtgga gtgggccaag cggatcccac acttctcaga gctgcccctg gacgaccagg 960 tcatcctgct gcgggcaggc tggaatgagc tgctcatcgc ctccttctcc caccgctcca 1020 tcgccgtgaa ggacgggatc ctcctggcca ccgggctgca cgtccaccgg aacagcgccc 1080 acagcgcagg ggtgggcgcc atctttgaca gggtgctgac ggagcttgtg tccaagatgc 1140 gggacatgca gatggacaag acggagctgg gctgcctgcg cgccatcgtc ctctttaacc 1200 ctgactccaa ggggctctcg aacccggccg aggtggaggc gctgagggag aaggtctatg 1260 cgtccttgga ggcctactgc aagcacaagt acccagagca gccgggaagg ttcgctaagc 1320 tcttgctccg cctgccggct ctgcgctcca tcgggctcaa atgcctggaa catctcttct 1380 tcttcaagct catcggggac acacccattg acaccttcct tatggagatg ctggaggcgc 1440 cgcaccaaat gacttaggcc tgcgggccca tcctttgtgc ccacccgttc tggccaccct 1500 gcctggaogc cagctgttct tctcagcctg agccctgtcc ctgcccttct ctgcctggcc 1560 tgtttggact ttggggcaca gcctgtcact gctctgccta agagatgtgt tgtcaccctc 1620 cttatttctg ttactacttg tctgtggccc agggcagtgg ctttcctgag gcagcagcct 1680 tcgtggcaag aactagcgtg agcccagcca ggcgcctccc caccgggctc tcaggacacc 1740 ctgccacacc ccacggggct tgggcgacta cagggtcttc gggccccagc cctggagctg 1800 caggagttgg gaacggggct tttgtttccg ttgctgttta tcgatgctgg ttttcagaat 1860 tcctgtgtgg ccctcctgtc tggagtgaca tcttcatctg ctctgaatac tggtgcccag 1920 ccagcccgtg acagcttccc cctaatcagg aggggacagc tgggggcgca agctggtgtg 1980 tcatcagcaa agacctcagc cgcctcgggg atgagagggg actcgtgggg caagcaagct 2040 gccctgtgct ctgagtgagg gggaaggtag cccctttttc caaagataac tcacagtttt 2100 gccctcgagc caatgagaac atgagctgcc ctctgtgcaa ggtttcgggg ccacctccag 2160 gctgcagggg cgggtcactc acccccctgt tttctctctg ccttggtgtt ctggtttcag 2220 actcccgact ccccgttcag accagagtgc cccggcccct ccccagcctg agtcttctcc 2280 ttgctctgcg gggtgggctg aggcttgtcc ttgtttcctg cagggctggc cctggctcgg 2340 gcagggtggg gcatcaccac ctcactggcc ttgctggagg cacagggctc tgcggacctg 2400 cagccatctg tgaggcccgc ggggatggga ggggaggagg gtggcctgtt ggtttccctc 2460 agagggggca ggtggcctgg agagagaggg gctcaggaac tgggagcctc gtgggtgggg 2520 cagatgctcc gcggcctgga gtggctctgc cggggcattg gtgggacccc tgctcaggcc 2580 ttctctctgg ctgccagttg tgtctaaaag actcttggaa tctgagaacc cggagtcgca 2640 gcgccctcgg gcctgggcca cacgcaggcc ctggtgggac cacccagcct ggtattgtcc 2700 acggacagcg ttgttoaccc agagccttac ttgggagcct cactgaacgc ctgctctggt 2760 tgaaggtggg gtgggggcgg ggcttggggc ctccctggct cagcccagtg cggcctggcg 2820 ctcctcccgc aggctctgcc cccgggctcc ggtggtgcgg ggccctctca ggttgaactc 2880 gcctcttttg cactggaagg ccctcccttt ggcctgagta cttttcccgt tcacgcctca 2940 gtcccgtgga cccagccttt gtcagtggca ggtgcctgaa cagagggtgg atggggggga 3000 taccggaggg ggtcttgtct tcccagccgc agtctaggaa tgatgcgggg gggtggacgc 3060 cttctccata gtctttcccc acctggagca ggggcttcct cagtggtgag gggagctgcc 3120 tacaggttgg accgggaggc agtggcttgg agaggcagct ttccagcctt ggtggggaag 3180 aaagtgtcca ttctttgcct tcctggagct cccagccaga gctgagctta ggcacccgag 3240 tggagcctgc agctgagtct gtgcccgaga caggctgtca gagattccag aagcctctcc 3300 tccccgccgc cctccacccc tgcctttcag cgttgtggat ccctagaggt ggccccctgc 3360 ccgatccacc gtcctgaggc agagtgttga gcctcatacc tgtaccaggt ccccggccag 3420 ctgggcccct cccaggcact gccaggaagc cccagctgcc cctggcgggt gtggtggaaa 3480 tggcaggagg gtgcaggtac tcttggggcc coagcggtgg gagtgcaaaa gacccaacgc 3540 caacaoctgg tgccttttgc agccagcgcc cacccatccg tgcccggacc cttgggaatg 3600 cccgcggctc cagaggaaaa agcccaggga cggggcctcc gttgcggggg gtcggctgct 3660 tcttgggaac tttgtcgttt ccggcgctgg ctggctggct ggctgtaaag cactgaagcc 3720 ccccggccgc caacccctga aagcagaacc tggcctccct ggccacagca gccttaccca 3780 ccgctotacg tgtcccgggc acttcocgca gccttcccgt ccctttctca tcggccttgt 3840 agttgtacag tgctgttggt ttgaaaaggt gatgtgtggg gagtgcggct catcactgag 3900 tagagaggta gaatttctat ttaaccagac ctgtagtagt attaccaatc cagttcaatt 3960 aaggtgattt tttgtaatta ttattatttt ggtgggacaa tctttaattt tctaaagata 4020 gcactaacat cagctcatta gccacctgtg cctgtccccg ccttggcccg gctggatgaa 4080 gcggcttccc cgcagggccc ccacttccca gtggctgctt cctggggacc cagggcaccc 4140 cggcaccttc aggcacgctc ctcagctggt cacctcccgg ctttgccgtt cagatggggc 4200 tcctgaggct caggagtgaa gatgccacag agccgggctc ccctaggctg cgtcgggcat 4260 gcttggaagc tggcctgcca ggaccttcca ccctggggcc tgtgtcagcc gccggccctc 4320 cgcaccctgg aagcacacgg cctctgggaa ggacagccct gaccttcggt tttccgagca 4380 cggtgtttcc caagaattct gggctggcgg cctggtggca gtgctggaga tgaccccgag 4440 cccctccccg tggggcaccc aggagggccc tgccggaatg tgcagcctgt gggtagtcgg 4500 ctggtgtccc tgtcgtggag ctggggtgcg tgatctggtg ctcgtccacg caggtgtgtg 4560 gtgtaaacat gtatgtgctg tacagagaga cgcgtgtgga gagagccgca caccagcgcc 4620 acccaggaaa ggcggagcgg ttaccagtgt tttgtgttta tttttaatca agacgtttcc 4680 cctgttttcc tataaatttg cttcgtgtaa gcaagtacat aaggaccctc ctttggtgaa 4740 atccgggttc gaatgaatat ctcaaggcag gagatgcatc tattttaaga tgctttggag 4800 cagacagctt tagccgttcc caatccttag caatgcctta gctgggacgc atagctaata 4860 ctttagagag gatgacagat ccataaagag agtaaagata agagaaaatg tctaaagcat 4920 ctggaaaggt. aaaaaaaaaa aatctatttt tgtacaaatg taattttatc cctcatgtat 4980 acttggatat ggcgggggga gggctgggac tgtttcgttt ctgcttotag agattgaggt 5040 gaaagcttcg tccgagaaac gccaggacag acgatggcag aggagagggc tcctgrtgacg 5100 gcggcgaggc ttgggaggaa accgccgcaa tgggggtgtc ttccctcggg gcaggagggt 5160 gggcctgagg ctttcaaggg ttttcttccc tttcgagtaa tttttaaagc cttgctctgt 5220 tgtgtcctgt tgccggctct ggccttcctg tgactgactg tgaagtggct tctccgtacg 5280 attgtctctg aaacatcgtg gcctcaggtg ccagggtttg atggacagta gcattagaat 5340 tgtggaaaag gaacacgcaa agggagaagt gtgagaggag aaacaaaata tgagcgttta 5400 aaatacatcg ccattcagtt cgttaaaaaa aaaaaaaaaa aaaaaaaaa 5449

<210> 26 <211> 2892 <212> ADN <213> Homo sapiens <400> 26 caaagatggc tgccacattg gcgctgtcat tttggtactg agcagagcga cgggcttaat 60 tcgacccaat ccaggccaga gtctttctct caggggcttc ctcgtgctca gctaatcctc 120 cgatcaatcc ttgggaatcc ctgggacctc ttcggtatcc ctactctcag ccagggatca 180 tgtcttgggc cgctcgcccg cccttcctcc ctcagcggca tgccgcaggg cagtgtgggc 240 cggtgggggt gcgaaaagaa atgcattgtg gggtcgcgtc ccggtggcgg cggcgacggc 300 cctggctgga tcccgcagcg gcggcggcgg cggcggtggc aggcggagaa caacaaaccc 360 cggagccgga gccaggggag gctggacggg acgggatggg cgacagcggg cgggactccc 420 gaagcccaga cagctcctcc ccaaatcccc ttccccaggg agtccctccc ccttctcctc 480 otgggccacc cctaccccct tcaacagctc catcccttgg aggctctggg gcoocacccc 540 cacccccgat gccaccaccc ccactgggct ctccctttcc agtcatcagt tcttccatgg 600 ggtcccctgg tctgccccct ccagctcccc caggattctc cgggcctgtc agcagccccc 660 agattaactc aacagtgtca ctccctgggg gtgggtctgg cccccctgaa gatgtgaagc 720 caccagtctt aggggtccgg ggcctgcact gtccaccccc tcoaggtggc cctggggctg 780 gcaaacggct atgtgcaatc tgcggggaca gaagctcagg caaacactac ggggtttaca 840 gctgtgaggg ttgcaagggc ttcttcaaac gcaccatccg caaagacctt acatactctt 900 gccgggacaa caaagactgc acagtggaca agcgccagcg gaaccgctgt cagtactgcc 960 gctafccagaa gtgcctggcc actggcatga agagggaggc ggtacaggag gagcgtcagc 1020 ggggaaagga caaggatggg gatggggagg gggctggggg agcccccgag gagatgcctg 1080 tggacaggat cctggaggca gagcttgctg tggaacagaa gagtgaccag ggcgttgagg 1140 gtcctggggg aaccgggggt agcggcagca gcccaaatga ccctgtgact aacatctgtc 1200 aggcagctga caaacagcta ttcacgcttg ttgagtgggc gaagaggatc ccacactttt 1260 cctccttgcc tctggatgat caggtcatat tgctgcgggc aggctggaat gaactcctca 1320 ttgcctcctt ctcacaccga tccattgatg ttcgagatgg eatcctcctt gccacaggtc 1380 ttcacgtgca ccgcaactca gcccattcag caggagtagg agccatcttt gatcgggtgc 1440 tgacagagct agtgtccaaa atgcgtgaca tgaggatgga caagacagag cttggctgcc 1500 tgagggcaat cattctgttt aatccagatg ccaagggcct ctccaaccct agtgaggtgg 1560 aggtcctgcg ggagaaagtg tatgcatcac tggagaccta ctgcaaacag aagtaccctg 1620 agcagcaggg acggtttgcc aagctgctgo tacgtcttco tgccctccgg tccattggco 1680 ttaagtgtct agagcatctg tttttcttca agctcattgg tgacaccccc atcgacacct 1740 tcctcatgga gatgcttgag gctooocatc aactggcctg agctcagacc cagacgtggt 1800 gcttctcaca ctggaggagc acacatccaa gagggactcc aagccctggg gcagggtggg 1860 gggccatgtt cccagaacct tgatggggtg agaagtacag ggcagaacca agaacataaa 1920 ccctccaagg gatctgcttg atatcccaag ttggaaggga ccccagatac ctgtgaggac 1980 tggttgtcto tcttcggtgg ccttgagtct ctgaatttgt cgggttctcc catgatttgg 2040 ggtgatttct caccctctgt ccttccccca gcacaaagca ctggccttgc ctccaggacc 2100 ttgcttcctt ctcatcttgc ctcattttgc ttcccatctg aagagtggaa atggggaact 2160 cccccagagg tggatactgg ggggcaggcc tcccaagctg atggacatga gagtagggcc 2220 ctgacaggcc ttcctcctct caaacctggc agatgggggc ctctctggaa gagggagggg 2280 ccctgtcact gtccagagtc tctttttaca cttcacctcc ttctgcagtc agactgaaat 2340 ataaaaaagg tggtggtggt ggtgaagggg ctggtggaga tgtaggaacc gatctgctat 2400 ttttaatttc ctgtgaggat agagacttgc agttagactc aaagaagtac tgtactttcc 2460 caggttgact aagaaatgcc agtggtggag gtgggtgttt gggaaaggca gggccctgaa 2520 atggcctgtc cctagggctc tccaagcact agccttccca gcttcccgcc gcccccccta 2580 tctcttcctg tctaacttgg ggaaggggcc tgggctgtga ggacagggcc cccacagggg 2640 atggtttcac gagtgtagtc ccggaggcct tccctttaca gctctcctcc agccctgggc 2700 acatagcata ggctggggac acaggatcct ggcctgagaa ttgaggggag gtggccagcc 2760 cgcagaggtg gggtgctggg gctgcatgat ttttgccctg cgtcccttct ctttggggct 2820 cctttcccct ctcatacata aaatcgcttt caaattaaaa tcgctgtttt ctggaaaaaa 2880 aaaaaaaaaa aa 2892

<210> 27 <211> 3915 <212> ADN <213> Homo sapiens <22 0> <221> caracteristica_misc <222> (106)..(126) <223> n é a, c, g, ou t <22 0> <221> caracteristica_misc <222> (1656) .. (1853) <223> n é a, c, g, ou t <22 0> <221> caracteristica_misc <222> (2304) .. (2423) <223> n é a, c, g, ou t <400> 27 gtccaggggc aagttcatcc tactctcgag tctaatgatg atgctcttca gtatgttgaa 60 gaattaattt tgcaattatt aaatatgcta tgccaagctc agcccnnnnn nnnnnnnnnn 120 nnnnnngaac gtgttcaaaa aagtttccct catccaattg ataaatgggc aatagctgat 180 gcccaatcag ctattgaaaa gaggaagcga agaaaccctt tatctctccc agtagaaaaa 240 attcatcctt tattaaagga ggtcctaggt tataaaattg accaccaggt ttctgtttac 300 atagtagcag tcttagaata catttctgca gacattttaa agctggttgg gaattatgta 360 agaaatatac ggcattatga aattacaaaa caagatatta aagtggcaat gtgtgctgac 420 aaggtattga tggatatgtt tcatcaagat gtagaagata ttaatatatt atctttaact 480 gacgaagagc cttccacctc aggagaacaa acttactatg atttggtaaa agcatttatg 540 gcagaaattc gacaatatat aagggaacta aatctaatta taaaagtttt tagagagccc 600 tttgtctcca attcaaaatt gttttcagct aatgatgtag aaaatatatt tagtcgcata 660 gtagatatac atgaacttag tgtaaagtta ctgggccata tagaagatac agtagaaatg 720 acagatgaag gcagtcccca tccactagta ggaagctgct ttgaagactt agcagaggaa 780 ctggcatttg atccatatga átcgtatgct cgagatattt tgcgacctgg ttttcatgat 840 cgtttcctta gtcagttatc aaagcctggg gcagcacttt atttgcagtc aataggcgaa 900 ggtttcaaag aagctgttca atatgtttta cccaggctgc ttctggcccc tgtttaccac 960 tgtctccatt actttgaact tttgaagcag ttagaagaaa aaagtgaaga tcaagaagac 1020 aaggaatgtt taaaacaagc aataacagct ttgcttaatg ttcagagtgg tatggaaaaa 1080 atatgrttcta aaagtcttgc aaaacgaaga ctgagtgaat ctgcatgtcg gttttatagt 1140 cagcaaatga aggggaaaca actagcaatc aagaagatga acgagattca gaagaatatt 1200 gatggttggg agggaaaaga cattggacag tgttgtaatg aatttataat ggaaggaact 1260 cttacacgtg taggagccaa acatgagaga cacatatttc tctttgatgg cttaatgatt 1320 tgctgtaaat caaatcatgg gcagccaaga cttcctggtg ctagcaatgc agaatatcgt 1380 cttaaagaaa agttttttat gcgaaaggta caaattaatg ataaagatga caccaatgaa 1440 tacaagcatg cttttgaaat aattttaaaa gatgaaaata gtgttatatt ttctgccaag 1500 tcagctgaag agaaaaacaa ttggatggca gcattgatat ctttacagta ccggagtaca 1560 ctggaaagga tgcttgatgt aacaatgcta caggaagaga aagaggagca gatgaggctg 1620 cctagtgctg atgtttatag atttgcagag cctgannnnn nnnnnnnnnn nnnnnnnnnn 1680 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 1740 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 1800 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnngtttgaa 1860 attccagagc ctgagccaac agaagctgat cgcatagcta tagagaatgg agatcaaccc 1920 ttgagtgcag aactgaaaag atttagaaaa gaatatatac agcctgtgca actgcgagta 1980 ttaaatgtat gtcggcactg ggtagagcac cacttctatg attttgaaag agatgcatat 2040 cttttgcaac gaatggaaga atttattgga acagtaagag gtaaagcaat gaaaaaatgg 2100 gttgaatcca tcactaaaat aatccaaagg aaaaaaattg caagagacaa tggaccaggt 2160 cataatatta catttcagag ttcacctccc acagttgagt ggcatataag cagacctggg 2220 cacatagaga cttttgacct gctcacctta cacccaatag aaattgctcg acaactcact 2280 ttacttgaat cagatctata ccgnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 2340 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 2400 nnnnnnnnnn nnnnnnnnnn nnnatgtatt gtagaaactg aaaatttaga agaaagagta 2460 gctgtggtga gtcgaattat tgagattcta caagtctttc aagagttgaa caactttaat 2520 ggtgtccttg aggttgtcag tgctatgaat tcatcacctg tttacagact agaccacaca 2580 tttgagcaaa taccaagtcg ccagaagaaa attttagaag aagctcatga attgagtgaa 2640 gatcactata agaaatattt ggcaaaactc aggtctatta atccaccatg tgtgcctttc 2700 tttggaattt atctcactaa tatcttgaaa acagaagaag gcaaccctga ggtcctaaaa 2760 agacatggaa aagagcttat aaactttagc aaaaggagga aagtagcaga aataacagga 2820 gagatccagc agtaccaaaa tcagccttac tgtttacgag tagaatcaga tatcaaaagg 2880 ttctttgaaa acttgaatcc gatgggaaat agcatggaga aggaatttac agattatctt 2940 ttcaacaaat occtagaaat agaaccacga aaccctaagc ctctcccaag atttccaaaa 3000 aaatatagct atcccctaaa atctcctggt gttcgtccat caaacccaag accaggtacc 3060 atgaggcatc ccacacctct gcagcaggag ccaaggaaaa ttagttatag taggatccct 3120 gaaagtgaaa cagaaagtac agcatctgca ccaaattctc caagaacacc gttaacacct 3180 ccgcctgctt ctggtgcttc cagtaccaca gatgtttgca gtgtatttga ttccgatcat 3240 tcgagccctt ttcactcaag caatgatacc gtctttatcc aagttactct gccccatggc 3300 ccaagatctg cttctgtatc atctataagt ttaaccaaag gcactgatga agtgcctgtc 3360 cctcctcctg ttcctccacg aagacgacca gaatctgccc cagcagaatc ttcaccatct 3420 aagattatgt ctaagcattt ggacagtccc ccagccattc ctcctaggca acccacatca 3480 aaagcctatt caccacgata ttcaatatca gaccggacct ctatctcaga ccctcctgaa 3540 agccctccct tattaccacc acgagaacct gtgaggacac ctgatgtttt ctcaagctca 3600 ccactacatc tccaacctcc ccctttgggc aaaaaaagtg accatggcaa tgccttcttc 3660 ccaaacagcc cttccccctt tacaccacct cctcctcaaa caccttctcc tcacggcaca 3720 agaaggcatc tgccatcacc accabtgaca caagaagtgg accttcattc cattgctggg 3780 ccgcctgttc ctccacgaca aagcacttct caacatatcc ctaaactccc tccaaaaact 3840 tacaaaaggg agcacacaca cccatccatg cacagagatg gaccaccact gttggagaat 3900 gcccattctt cctga 3915

<210> 28 <211> 2757 <212> ADN <213> Mus musculus <400> 28 cgccttcaag ttgcccggag cgcgtctggg accggcagac ctgtcccgga gcgcgtagat 60 ccgcacgcac gcacgcgccg cccacgtcca gcttgcgaat ccgagggacc cgttccaata 120 atgccccgga aggcagccag tccagaggag gcggcggggg agcccggtcc tgaggagatg 180 gaggctgggc ggccgcggcc ggtgctgcgc tcggtgaact cgcgcgagcc ctctcaggtc 240 atcttctgca atcgcagtcc gcgcgtcgtg ctgcctttgt ggctcaactt cgacggbgag 300 cctcagccct acccgatctt accaccgggc accggtcgcc gcatccacag ctaccgaggt 360 catctttggc tcttcaggga tgcggggacc catgatggac ttctggttaa ccaaacggag 420 ctgtttgtgc catccctcaa tgtcgatgga cagcctattt ttgccaacat cacattgcca 480 gtgtataccc tgaaagagcg gtgccttcag gttgtgcgga gcctggtcaa gcctgagaac 540 tacaggagac tggacatcgt caggtcactc tatgaggatt tggaggacta cccaagtgtg 600 cggaaggaca tacagcgact gagccaagag caccttgaga gtcagcacct ggaagaggag 660 ccttgaagga gtccatggag attaagtgtt cctgagtttc acccttgatg gtccgagatt 720 gatctacaca taggacaggt cactttcttt cagttttaaa atggttcatt cttggagtaa 780 aactatccat cacgtaaaag aaagttaact aacatccctg ggctttgtag tgtttaagaa 840 taaacatgca aagtgccact gcgtctgccc tttgtagagc actcacccga gggaggaaga 900 cgttttcagt tttgcttcct ggtgagctgg aagttgagtg taaggatgac tgtgtaataa 960 agctcagcag caggagttgt actgtgtcct ttcatttgag cagagggctc ttgcttggga 1020 aggcagagaa ggcccttccc aaacgctggg acagacctcc tgtggaggcc cgctgcctaa 1080 agcgtggagt cttcagtoat gaatgttgga cgaagaaacc attggatgct tggtgggaga 1140 gttgggaggg cctggctctt tgtctgagga gagccttaag tgttcatgta aggaacagct 1200 tagcagcttc tgattttccc acgtcccagc actttctctc tgttttttat tttatttttg 1260 agacttttgt atagcccagc cagcctcagt cactcagcag aggattcctg acctgtctgg 1320 gattatgtct cctgacattg ggaacacatg tgtgcacaca gcctgctctg ctcttccttt 1380 tcccatgttg agacgggctc ctgctgtagt cctgcctggc ctgagctgga gtcggtcctg 1440 cctcctgacc gaccgtctgg ctgctttcta agctgggtag acttcccata ctcactgtta 1500 cagacagtta cagcagagaa gaaccatcct tgtgtaagtc tggttttgag agctcctgtc 1560 tctgaggaaa ggaaactgtt ggcaggagca gggatttctg ttccttcttg tcaaccccta 1620 gcattccact ttgttttggc aggcgctggt tctgctttgt aggtggaagt gaagcttcca 1680 ctcagccaca gactccagac agtgggtcac agagcagtct ggaatgtgta gcagtcttat 1740 ggatggtcac agcttttctt acatattcat attctatcaa acgttttgta aagtataatt 1800 ttttatttat ttttaatccc cttagagaaa aagtaaaagt agagaagcct gggtattgtg I860 tacacaacag aaaggacagt caaggaaagg gaagcagaaa ggctcttatg tactctcagc 1920 tccatgcaac ccctgtaact ggcgcatatg tagggcatat tttaattggt taaagcagtt 1980 tgttgtggct gaggtcataa gatatataca gttttgtatc ctgatttttc actgaacttc 2040 attgtttttt gtttgcttgc ttttcccttc ttctttgttt tttactttat tgagataggg 2100 tttctctgta gcccaggctg tcctagaact ccctttgtag accaaacatc tgattactga 2160 cctcacatgg agagatctgt ctcttacttt ccagcgctgg gattgaagta ggcctaatct 2220 tcatctaact tcttagcttg tcttttccat gttactacac acactgtgta aataccagtg 2280 tgctaccctc cttctttgag ggtgactgtt gggagtattt gtccaaatcc tgggcacctt 2340 gagtgcagac tgatgctcta agatcagcaa aatgactgaa ctacatccta acacttccca 2400 gtgtcctctc agtgtctctt cttatctgca gcattgcagg agtgaagtgg ccacagacca 2460 gtgtggaggc ctgtgtgtgg gaagtcagca ggtgccaagc tattgaaaca ttggttttat 2520 ttttttaaac cgatctctgt ctctaaaaga tgtgtatgtt tgtgttattc agctggaagt 2580 ttgaatactg ttctctgtgc tgtccaacaa gtgaagagtt atgaaatgag ccacttgtcc 2640 tgggacatcc tgtaatgagt tcctcgggct tttctcctgt gagttttctg aaaaaagctg 2700 acctttttag tacaataaac ggtgctaatt gaaggaaaaa aaaaaaaaaa aaaaaaa 2757

<210> 29 <211> 2301 <212> ADN <213> Homo sapiens <400> 29 agcagagcgg acgggcgcgc gggaggcgcg cagagcttto gggctgcagg cgctcgctgc 60 cgctggggaa ttgggetgtg ggcgaggcgg tccgggctgg cctttatcgc tcgetgggce 120 catcgtttga aactttatca gcgagtcgcc actcgtcgca ggaccgagcg gggggcgggg 180 gcgcggcgag gcggcggccg tgacgaggcg ctcccggagc tgagogcttc tgctctgggc 240 acgcatggcg cccgcacacg gagtctgacc tgatgcagac gcaagggggt taatatgaac 300 gcccctctcg gtggaatctg gctctggctc cctctgctct tgacotggot cacccccgag 360 gtcaactctt catggtggta catgagagct acaggtggct cctccagggt gatgtgcgat 420 aatgtgccag gcctggtgag cagccagcgg cagctgtgtc accgacatcc agatgtgatg 480 cgtgccatta gccagggcgt ggccgagtgg acagcagaat gccagcacca gttccgccag 540 caccgctgga attgcaacac cctggacagg gatcacagcc tttttggcag ggtcctactc 600 cgaagtagtc gggaatctgc ctttgtttat gccatctcct cagctggagt tgtatttgcc 660 atcaccaggg cctgtagcca aggagaagta aaatcctgtt cctgtgatcc aaagaagatg 720 ggaagcgcca aggacagcaa aggcattttt gattggggtg gctgcagtga taacattgac 780 tatgggatca aatttgcccg cgcatttgtg gatgcaaagg aaaggaaagg aaaggatgcc 840 agagccctga tgaatcttca caacaacaga gctggcagga aggctgtaaa gcggttcttg 900 aaacaagagt gcaagtgcca cggggtgagc ggctcatgta ctctcaggac atgctggctg 960 gccatggccg acttcaggaa aacgggcgat tatctctgga ggaagtacaa tggggccatc 1020 caggtggtca tgaaccagga tggcacaggt ttcactgtgg ctaacgagag gtttaagaag 1080 ccaacgaaaa atgacctcgt gtattttgag aattctccag actactgtat cagggaccga 1140 gaggcaggct ccctgggtac agcaggccgt gtgtgoaacc tgacttcccg gggcatggac 1200 agctgtgaag tcatgtgctg tgggagaggc tacgacacct cccatgtcac ccggatgacc 1260 aagtgtgggt gtaagttcca ctggtgctgc gccgtgcgct gtcaggactg cctggaagct 1320 ctggatgtgc acacatgcaa ggcccccaag aacgctgact ggacaaccgc tacatgaccc 1380 cagcaggcgt caccatccac cttcccttct acaaggactc cattggatct gcaagaacac 1440 tggacctttg ggttctttct ggggggatat ttcctaaggc atgtggcctt tatctcaacg 1500 gaagccccct cttcctccct gggggcccca ggatgggggg ccacacgctg cacctaaagc 1560 ctaccctatt ctatccatct cctggtgttc tgcagtcatc tcccctcctg gcgagttctc 1620 tttggaaata gcatgacagg ctgttcagcc gggagggtgg tgggcccaga ccactgtctc 1680 cacccacctt gacgtttctt ctttctagag cagttggcca agcagaaaaa aaagtgbctc 1740 aaaggagctt tctcaatgtc ttcccacaaa tggtcccaat taagaaattc catacttctc 1800 tcagatggaa cagtaaagaa agcagaatca actgcccctg acttaacttt aacttttgaa 1860 aagaccaaga cttttgtctg tacaagtggt tttacagcta ccacccttag ggtaattggt 1920 aattacctgg agaagaatgg ctttcaatac ccttttaagt ttaaaatgtg tatttttcaa 1980 ggcatttatt gccatattaa aatctgatgt aacaaggtgg ggacgtgtgt cctttggtac 2040 tatggtgtgt tgtatctttg taagagcaaa agcctcagaa agggattgct ttgcattact 2100 gtccccttga tataaaaaat ctttagggaa tgagagttcc ttctcactta gaatctgaag 2160 ggaattaaaa agaagatgaa tggtctggca atattctgta actattgggt gaatatggtg 2220 gaaaataatt tagtggatgg aatatcagaa gtatatctgt acagatcaag aaaaaaagga 2280 agaataaaat tcctatatca t 2301

<210> 30 <211> 3672 <212> ADN <213> Homo sapiens <400> 30 gcccggttac ttcctccaga gactgacgag tgcggtgtcg ctccagctca gagctcccgg 60 agccgcccgg ccagcgtccg gcctccctga tcgtctctgg ccggcgccct cgccctcgoc 120 cggcgcgcac cgagcagccg cgggcgccga gcagccaccg tcccgaccaa gcgccggccc 180 tgcccgcagc ggcaggatga atgatttcgg aatcaagaat atggaccagg tagcccctgt 240 ggctaacagt tacagaggga cactcaagcg ccagccagcc tttgacacct ttgatgggtc 300 cctgtttgct gtttttcctt ctctaaatga agagcaaaca ctgcaagaag tgccaacagg 360 cttggattcc atttctcatg actccgccaa ctgtgaattg cctttgttaa ccccgtgcag 420 caaggctgtg atgagtcaag ccttaaaagc taccttcagt ggcttcaaaa aggaacagcg 480 gcgcctgggc attccaaaga acccctggct gtggagtgag caacaggtat gccagtggct 540 tctctgggcc accaatgagt tcagtctggt gaacgtgaat ctgcagaggt tcggcatgaa 600 tggccagatg ctgtgtaacc ttggcaagga acgctttctg gagctggcac ctgactttgt 660 gggtgacatt ctctgggaac atctggagca aatgatcaaa gaaaaccaag aaaagacaga 720 agatcaatat gaagaaaatt cacacctcac ctccgttcct cattggatta acagcaatac 780 attaggtttt ggcacagagc aggcgcccta tggaatgcag acacagaatt accccaaagg 840 cggcctcctg gacagcatgt gtccggcctc cacacccagc gtactcagct ctgagcagga 900 gtttcagatg ttccccaagt ctcggctcag ctccgtcagc gtcacctact gctctgtcag 960 tcaggacttc ccaggcagca acttgaattt gctcaccaac aattctggga ctcccaaaga 1020 ccacgactcc cctgagaacg gtgcggacag cttcgagagc tcagactccc tcctccagtc 1080 ctggaacagc cagtcgtcct tgctggatgt gcaacgggtt ccttccttcg agagcttcga 1140 agatgactgc agccagtctc tctgcctcaa taagccaacc atgtctttca aggattacat 1200 ccaagagagg agtgacccag tggagcaagg caaaccagtt atacctgcag ctgtgctggc 1260 cggcttcaca ggaagtggac ctattcagct gtggcagttt ctcctggagc tgctatcaga 1320 caaatcctgc cagtcattca tcagctggac tggagacgga tgggagttta agctcgccga 1380 ccccgatgag gtggcccgcc ggtggggaaa gaggaaaaat aagcccaaga tgaactacga 1440 gaagctgagc cggggcttac gctactatta cgacaagaac atcatccaca agacgtcggg 1500 gaagcgctac gtgtaccgct tcgtgtgcga cctccagaac ttgctggggt tcacgcccga 1560 ggaactgcac gccatcctgg gcgtccagcc cgacacggag gactgaggtc gccgggacca 1620 ccctgagccg gccccaggct cgtggactga gtgggaagcc catcctgacc agctgctccg 1680 aggacccagg aaaggcagga ttgaaaatgt ccaggaaagt ggccaagaag cagtggcctt 1740 attgcatccc aaaccacgcc tcttgaccag gctgcctccc ttgtggcagc aacggcacag 1800 ctaattctac tcacagtgct tttaagtgaa aatggtcgag aaagaggcac caggaagccg 1860 tcotggcgcc tggcagtccg tgggaoggga tggttctggc tgtttgagat tctcaaagga 1920 gcgagcatgt cgtggacaca cacagactat ttttagattt tcttttgcct tttgcaacca 1980 ggaacagcaa atgcaaaaac tctttgagag ggtaggaggg tgggaaggaa acaaccatgt 2040 catttcagaa gttagtttgt atatattatt ataatcttat aattgttctc agaatccctt 2100 aacagttgta tttaacagaa attgtatatt gtaatttaaa ataattatat aactgtattt 2160 gaaataagaa ttcagacatc tgaggtttta tttcattttt caatagcaca tatggaattt 2220 tgcaaagatt taatctgcca agggccgact aagagaagtt gtaaagtatg tattatttac 2280 atttaataga cttacaggga taaggcctgt ggggggtaat ccctgctttt tgtgtttttt 2340 tgtttgtttg tttgtttgtt tttggggggt tttcttgcct tggttgtctg gcaaggactt 2400 tgtacatttg ggagttttta tgagaaactt aaatgttatt atctgggctt atatctggcc 2460 tctgctttct cctttaattg taaagtaaaa gctataaagc agtatttttc ttgacaaatg 2520 gcatatgttt tccacttctt tgcatgcgtt taagtcagtt tatacacaaa atggatttta 2580 ttttttagtt taactgtgtt tctccgacag ctcacctctc tctgaccacc cagccatttc 2640 cttectgtgc tccacgttct tctgtgtgat taaaataaga atattatttt tggaaatatg 2700 caactccttt tcagagatca ggagggattt atgtagcagc tatttttact gcaaaagtaa 2760 ttcactggaa aaaaaatgta atttgtaaga aagctttatt tttatctcag ctctatgtaa 2820 agttaaagtt actgtacaga gctgaaggac ggggggcggt aggggtcttg atgaaacctc 2880 ttgaacgaag cacagtttgt cccatctttg ttcactcgtg tgtctcaacc atcttaatag 2940 catgctgctc ctttttgctc agtgtccaca gcaagatgac qtgattctta ttttcttgga 3000 cacagactat tctgaggcac agagcgggga cttaagatgg gaaagagaaa gcatcggagc 3060 cattcattcg gagaaaacgt tttgatcaaa atggagactt ttgtagtcgt ttcaaaagag 3120 cacctgagtc atgtgtattc ccggccttta taaatgaccc ggtcaagttg gtttcaaagt 3180 ccgacaggct tgtctgttta ctagctgcgt ggccttggac gggtggctga catctgtaaa 3240 gaatcctcct gtgatgaaac tgaggaatcg ggtggccggg caagctggga agagcaaagc 3300 cagagctgcg ctgcctcaat acccacaaaa gaccattccc agtatacata agcacaggat 3360 gtttttctca agagggatgt atttatcact tggacatctg tttataatat aaacagacat 3420 gtgactggga acatcttgct gccaaaagaa tcctaggcag tggctcattg tatgtgaggt 3480 tgaaccacgt gaaattgcca atattaggct ggcttttatc tacaaagaag gagtttcatg 3540 gggttcagcc taacagttat ggaaactaca gtccttataa accattggca tggtaataaa 3600 cagatcttaa gtataaaaat tttgtaattg ggcctttact ctctcaataa taaagtattt 3660 tgtttatata aa 3672

<210> 31 <211> 16479 <212> ADN <213> Mus musculus <400> 31 totagaggtg tgaccgggcg cgtgagacca caggggagcc agacaaacgc ttgcttcctt 60 aagttgcttc ttggcagaca cttgggcata acagtaaggc aattatctgg tactcatccc 120 accttatgtg tccttgaata tgatggctct agggacctca tagagactga gtcacatggt 180 accttccccc tttattttga gaatttattt tgtagaaaaa acgcaaataa aaataagtaa 240 ataaaattta ttttttgtgt tctatcatct atctatctat ctatctatct atctatctat 300 ctatccttcc ttccatctat ctatttttac tccatccatc catccatcca tccatccatc 360 catccatcca tctacctatc tatttttact tgggcctgtc agtccccatg gaactagact 420 tgtacatgag ggtgggctat ttgagcgggt gctgggtggg agtcaaactt gggtgaagag 480 caagtgctct taaccactga gtcatctctc tagtgcttgg cctttttggg attagctttt 540 tgcattgagt attgtgtcct aaaagcctat caatttccca catttttcct ctctcttctt 600 tctttcttcb gcctcactat gtagactagg ctagtctcaa acttggatcc tctgccctgg 660 cctcctatgt gttggatttt aggtatgcat caccaoatgt ggctagatgc ctgccctctc 720 tccctctctc cctcccttcc ttcctatctg tcttttcttg aaaaaagaac taacatatct 780 caggctggcc ttgaactcat taagtagcca aggatgacct tctgcttcca tcttctgagt 840 gctgagatga caggcatgag tactgtgccg gtttatggag tgtcaaggac tgaacccagg 900 gcttagtgca tgctaggtaa acatgcgtca caccgagtca catctccaga ccttcttcac 960 ctttaaaaat tatactgatt ggtggttagg tatgtgtgta tatgtgtacc acaacacaca 1020 tgtcaaggtc agaggacaac taatgattat cttcttacac tatatgggcc ctggtatcca 1080 acttcagatt gccaggcttg gtggcaagca cccattttac ctactgagcc atctcaaaga 1140 ccctacacca ttttaaaagg gagttatttc tttctatatg tatggggggt ttgcctctgt 1200 atgtctgtgc cccatgccca tgaaggccca cagagaccag agagagcata gagtctcctg 1260 taactggaat tacagatagt tgggatctat caagtggagg ttaggaacct aactcaggtc 1320 ttctgoaaga gtagcagtca cggagooatc tottcagtcc caotctctco ttcattttga 1380 agaataggcc aaactacatt ctgcttatcc attcacccac cagtggatgt aggcttgctc 1440 tgcatatgcc tattttaaga aatgctgctg tggacagatg tatgagtatt gtgtcatctc 1500 ctcttagtgt ctctgcatac aaatgattgt ttctgcatgt atgcatatgt atcattttcc 1560 tctgactaag aatgtttttt cctttcctgg tttcacataa tgcgattgcg atgtatcttc 1620 tttgttctca gattttgctg agctctctgg atctgtgagc ttatgatttt tatctagttt 1680 ggaaattttt cagctctttt cctotocagt tgtattttct gcctaatttc ttgttctcat 1740 tcaggagtgt gtttggcacc atgcttctcc tcacgtgcct gtctgtgctg acctttggat 1800 gccacccact tctatgcctt caaattcatt aacctttctt ttcacagcat ccaatttgcc 1860 actgçrtgcat tttccattcc agatgctggc gttcttgttc atctccagaa ctttagggct 1920 gtottcgctc atgtaaatac ctcctgtgcc gccacttcac cttcagcctg tgaaacccag 1980 tcacagtaat atttttgctg accttgtcta tgactggtga tactggttca ccccacatag 2040 ttttcttttg gtcacagaaa tgaaaaaagg ttactgagac aggttggggt attagacact 2100 gcaaccgtaa atccttaaaa atatatataa ttttaagatt tataggatgt gtgtgtgtgt 2160 gttgtgtgtg tgtttgtgtg tgacacatgt acatatgatg cccccaagag tgcagaagaa 2220 ggcattggat cccctagagc tagagtgtta ggaatttgta agccacttta cataggtatg 2280 gggaactgac ctctggtcct cttgcaatac taataactgt tcttaactac taagctatct 2340 ctctagctcc tttttctttt taactttgat tttatttccc ttattttccc tccccctgtg 2400 tgtgtgtgtg tgtgcgcata tttgtgtttg gacatttaag ttcgtgtatc tatgtgtgta 2460 tatgtttgtg tgtgtgtata tgtatgtaga tctttatata tgtgtgtgca tgtttgtatg 2520 tatatgcaca tatgtgtgtt tgtagcatgt atatgtgtgt atttatgtat gtttgtgtgt 2580 gttcatgtgc acataaaaga agcatgtgca cacagaagca agtgcatgtt tgtgcatata 2640 tgtgtatatg tttgcatata ggtatatgtg tçrtatatatt tgtatgtgca cacatgtttg 2700 tgtgtgtgtg cgtgtgcgca cgcacatgca cagagaccag aaatcaaact caggtgtatt 2760 tctctgaaag tgaggctttt gagcatagtc tctctgggga cctagggcct gcaagctcca 2820 gggatccacc tgtctctgtt tccccagcac tgagggttct ggagatcttg cctgcatggc 2880 aagcatttac tgactgagcc ctccttcaag tcottottco ttgtttctct ttgacttcag 2940 agtgagctac atgtcacctg gatcttcctt tctgccttta ttgcatctag cctgtgcttg 3000 ggacacttgc tttccaggat gtcttgccat cggtaaggac accctagaat atttgctgtt 3060 gtatatatgg cagettggtc caatgtctga tgatttggta aaggtgtctt ctactagcag 3120 gccaagtggc ttcttcccag tggcactgtc cacttccagg gcatggcttg gaaccaagct 3180 gtctctccaa ggtgtcagtg agggtttcag ggtgtcataa tggtaggcca tctatgctga 3240 gccagctgat cctctgcctg tcattcacca gtaaacttgg ggagtgtccc cttttgttcc 3300 atgagaccca ggcatgttat agaatgtaga ctccattgtt gagtgcctca gagccacctg 3360 atagaggttg ttgaaagatg gctgggtctg cgccattccc aaggggatgg aatggacaag 3420 ggagccacac aggcagatgg ctctcagaac agcatgtgga aagctgagac tgaatgccaa 3480 gggctgggtc tcatctgact gggtttgtcc aggttgtcoo tacttggaga tggagctcag 3540 agagtgggag gcaaactcca ttctcaggaa tccagagtag acgtggggca tcctccaagg 3600 gcagagtgga aatctagctg gagaagaggt ctggccacag atggacaact agagggaaag 3660 aagacagatg gtactgatgt catgagtatg gagacttccc tgtgaaggaa acatgggagt 3720 gacatgggct gagggaaaag gaggacaaga tcagcctgcc atgaattaag tttgggaagc 3780 tgtggagcat tgaggttcag tccacatgtc acatggataa aaactgtggc ttgtaccaga 3840 agctttgcct gcgttagttc tgtcccaaag ctaaaggggt aggggagatg gttcagtggt 3900 tctatttttt tttttttttt tttttttttt ttttggacgg gtttctctgt atagccctgg 3960 ctatcctgga actactttgt agaccaggct ggctttgaac taaaatccgc ctgccttgcc 4020 tccaagtgct gggattaaag gctgtgccac caccgcccgg caagaacact agttcttaac 4080 ggctttcaag gacccagttt cacttgtgct cttccagtat acacagttag ttcccagcac 4140 ccatgtagta gctacaacca ctcagttcca gagaacctga gtctctcttc ttgcctctgt 4200 ggatactgac atatatactg caagcaaacc acccacactc aacataaaat aaatattgga 4260 ttttaaaatt ttaaaccatt aaagcagtta aaaaaggtaa aaattaggct gagatagcta 4320 agttggcatg tgctggctgt gcatgagaac ctggctttga actcagagtc tacttctaaa 4380 agccagggat gctagcttgt aatcccatca ctgggaagac agagtcaaag gatccctggc 4440 accagctggc tagtgagccc ctgatacaag ccagtaagaa tccctgtctt aaagtttgga 4500 gctgagacga aaggatggac catgtagaga ctgccatatc cagggatcca ccccataatg 4560 agcttccaaa cgctgacacc attgcatgca ctagcaggat tttatcgaaa ggacccagat 4620 gtagctgrtct cttgtgagac tatgccgggg cctagcaaac acagaagtgg atgctcacag 4680 tcagctattg gatggatcat agggctccca atggaggagc tagagaaagt acccaaggag 4740 ctaaagggat ctgcaaccct ataggtggaa caacattatg aactaaccag taccccggag 4800 ctcttgactc tagctgcata tgtatcaaaa gatggcctag tcagccatca ctggaaagag 4860 aggcccattg gacttgcaaa ctgtatatgc cccagtacag gggaacgcca gggccaaaaa 4920 aaatggaatg agtggtaggg aagtgggggg gagggtatgg ggaacttttg gaatagcatt 4980 ggaaatgtaa taggaaaata tgtaataaaa aataaaaata aattaaaaaa aatccctgtc 5040 ttaaacaaaa caaaacaaac aacaaaaaac ccaaacacaa caaaaggata aatggcacaa 5100 cacccaaggt tgtcctctgg cacatattct acacacagtg catgtatgca ccgatacacc 5160 ctcacacaca tactcttatg cacacagtat acatatgcac ccacacatcc tcacacacac 5220 tcttctacac acagcgtaca tatgcactca cacaacctca tatgcatact cttatgcaca 5280 cagtatacat atgcatccac acaccctcac acacactgtt ctacacacaa tgcacatatg 5340 cacccacaca cactcacata catactctta tgcacacagt atacatatgc atccacacac 5400 cctcacacac agtcttctac acacagttca cgtatgcacc acacacactc acacacatac 5460 tcttatgcac acagtataca tatgcaccca catccataca aacatgtata cacacacaca 5520 cacacacaca cacacatcaa cattaaaata acattttgta gtacataaac aggaccagaa 5580 gttccagaca gtgtctatac ttcttttgct gggaaacatt tatggtgttt ttgtaatgtc 5640 tgtggcagca tttgctccct agcatgtgac actgactgta tagcctgcaa agcatgacag 5700 atttgctaac aggtcctcag aaaaagctgt tttgccccat gcttgaaagc tcaaggatgg 5760 agtcacacag ccagggataa atgacccctg caaaggagag gtgccaagga gcaggcaggg 5820 cacaagccat gtcaaaatct tccagctgat ttttgagaca taatcatgca ccacacactt 5880 cattgaacca ttaaaccaca gccatgtaaa ctgtagcata gtcagcttgt gtgcatgtat 5940 gtgccatagc caattgtcca gattgtgtgg agatcagatt ctccagaata tcagtccttg 6000 cctgctacct ttctgagaca aggtctctct gttgttgttg tgtattctaa gctaactgac 6060 ccttgagctt acagtgagtg tcgtctccgt ctcccattgt gtcatagcaa tgctgaggta 6120 caggaatgbg ttcccatgcc aggctttaca tgggttctgg ggattcaact tcaggccact 6180 gtgcttgcat ggcaagcact ttatctgctg agccatttcc ccàagctcct tagaacattg 6240 tgattaaaag gaaattcata ccctgtagcc agtacctccc cctcattctt gtccccgtgt 6300 otatttctgt ctctgtggat tggcctgttc tggacagttc ttgtaaatga catcatgtaa 6360 tatgtggtct ttcggttttt ccttctttca ctcactcatg tctaccaaca ccatgatgcc 6420 agtcagtgtt ttatttcttc tcttggctga acaatatttc cttctgagtc agttcatgct 6480 ttatccatcc atttgtctgt tatggacatc tggctgtttc aaaacattta aatgaagatc 6540 acatggctaa ggatagagcc agagcccaag ccccccaaaa gagatgtatg aaactcttat 6600 gatcagggga gaactgcttc tggagcaaga gaactgccac caggatggtt agaggatgtg 6660 ggtacgtgaa gttaagaaat gaaggggcac acctaggaga cgccaatccc tagggaactg 6720 tcacctttaa gctgaggaag gtaggttggg cttgcagaaa gtacgagggc caggatgggg 6780 gaggggccaa ggtgggaaag gtgctgagta ggatgagatg ctggctttat agaagtaggg 6840 tatgtaccag cctgagagga aggaaatatg gtgagacccc tgaaagagtc gtgagtcttt 6900 acacacacac acacacacac acacacacac acacacacac acagacacac acacagacac 6960 acggtgatgt acctaagttg ctagattgcc tagaatgcac cacattgtct agcatgtatc 7020 atatatgaag ccctgggttc catctccagc abcacataca atgagtgtga cggtgcatgc 7080 ctataatcta tctggagata taagaagaag atagacgttc tgaagttcac agtcatcctt 7140 agctatgtag tgaattaagg gctaacctaa gcttcaggca gactctccca ccaccacccc 7200 taaatggagg aaaagtacaa aaaacaactt aggaaaggca gggaggaaac agggcagcag 7260 tggtctccgt acagtgaggg tttgcagatc aaacctcctc agggcaccag gatacaaact 7320 gtttccatct cttctgtata tgtgtgcatg cttgcgtgtg caaggatgag cacagcagtg 7380 tgtatggagg ttggaggata tcttggatgt tggtccttcc cttccagcct gtttaagata 7440 gacgttgttg ttcattattg cagtcctggg gctaagctgg cttgaaagtt tgaaagaatt 7500 ctcttcttgg catcttgggt ttctatgggt tctgaggatt tgaactcagg tcctcacact 7560 tgcacagcaa gtgctttact taccattctc cccagaccaa ctggattgct ccaaacagca 7620 gagaagtgac tagacttatc caagtgctct tagcagacac ccgggaaatt tcgactcact 7680 gcccacttcc cacagcaagg ttatcaaaag gctggattag gatgatacag ccttgacgaa 7740 tcctggagag tcatggaacc tgcaggcagc cccacactgg cagtacatgc tccaaggcag 7800 tgcgaaagca gagagaagcc tggttttggt agccctcccc cagtcggata tttacaaaga 7860 aagtaactcc aggttactac ccacaggata gaccacttga accctatagg tcttgcttgg 7920 ctcccaagca cctacctagt cctttgaggg aaaaattggg cttgctacgg ccttgagagc 7980 acacttctgg gacaatgggg caaaactgag actttgacaa ggtcagtgca tttcccttcc 8040 ccttcaacct tccctccacc ggcctcaggg gaaggatggg actgagaggt ctgctggaat 8100 ccgaagaagt gttattgaac aaaaagtcca ggaaccgaac aaaaactagt ctgggtagat 8160 tcaccattag gaaaagagac ccagacttgg agagctggct gtaaggtgca gatgggtgac 8220 agtgtgagaa aggagtggac ttgattgtat tctctcaggt cagggcaacc ggtcctgggg 8280 attcttgaaa acacagaggc atggggtgtg catgaagggg ctaaatgggt acaggtgccc 8340 aaggaacatg aaatttccca ttactggtct gaaccactcc tcaagccctt ctcacactca 8400 aggggcacag gtgtgctcct gcaatgcgtg gacaccgggt cctggtggag gageagggtg 8460 gggcggagtg ggcgtggagc cttgtgcgag acactccccc atctctggag ccacgcgcca 8520 ggcgtacgct tccttctggc cccggcatag gaccgcgcca attgtcattg gccaaacggg 8580 cgatcccaga ttggctgaga ccccggctcc cgcctcctcc gccaggggga gggacgtggg 8640 tgccggttta gaggctcgtg ctaccctagg gggtcgcgct cttctgcctc ctacctcttg 8700 gtcaccgcaa agcttggtcc ggttcttcat ccggctgcaa gcgctaggtg tgcggagacc 8760 tggcagctct tggggcttaa gggctgagca ccaggacggg tggaggtgcc tgtagagtac 8820 attcggaccc tctctcggac cctctctcag cccctgagtg tgcgggacct gcggagcgca 8880 gttcgggatc tgcactcgag gatttttcga ggacgcaata agctaagcat ctgcccggag 8940 catggaagca cgtcagtagg ccatgaactg cacccgggag gggtgggggt ggaagcgcac 9000 ggtgtcagct ttgcagaatg tgtacgccaa ggggagggtg aagcgtggcg ggagggcgag 9060 gcgaaggaag gagggcgtga gaaaggaggc ggtggcgggc ggaggagagt tatctatact 9120 ttttaaaaaa aaggagccgc ttgagccgcg taaagggaga cttggggagc gcctgacagc 9180 acgcgcggga cacgagagta ccacgcttcc ctactctttc agaccttgac tggtacgggg 9240 tcccaggact gcaggaggcc agcgacgcgt gccctaggga gtcctgcagc agtgccctgc 9300 ctgaggcccg tgaaggtgca aacgtccaot tcccaccgca cccggttcct cgcgagcact 9360 tttcctgtgc cgcaccagaa ctcgtagcag gggcccaggg gctgaatgca agcttgatgg 9420 acggcggcgc gctgcccaga ctcatgccoa cctcgtctgg agtcgctgga gcctgcgctg 9480 ctcggcggag acaagcgtct ccggaattgo tgcgctgcag ccggcggcgg cgatctggag 9540 caaccgaggc cagcagcagc tcggctgccg tggcacgccg caatgagcgc gagcgcaacc 9600 gcgtaaagct ggtaaacttg ggcttccagg cgctgcggca gcacgtgccg cacggcggcg 9660 ccaacaagaa gctgagtaag gtggagacgc tgcgctccgc ggtagagtac attcgtgcgc 9720 tgcagcggct gctcgcagag cacgacgcgg tgcgtgccgc gctcgctggg gggctgttaa 9780 cacccgctac tccgccgtcc gatgaçrtgcg cgcagccctc tgcctcccct gccagcgcgt 9840 ctctgtcctg cgcctctacg tctccgtccc cggaccgcct gggctgctct gagcctacct 9900 ccccgcgctc cgcctactcg tcggaggaaa gcagctgcga gggagagcta agcccgatgg 9960 agcaggagct gcttgacttt tccagttggt tagggggcta ctgagcatcc caccccccta 10020 aggtaagttc caggacggcg gggaggcgaa gcagtaaggg agacacgtgg tgggcgggcc 10080 tgacacttag cgccacgggg accctgtgca gccaggactc agctggggcg atcacttgga 10140 tttcgcgcac gcttcatttt tcctcaacct ttttcaagcc tgagcaagac cggcgtttgt 10200 ttgtccggga ttgcaaaact tcctctcaga gctctgctgt gggtggggga aggggaggcc 10260 aggggagggg agcggcctca gggccgggcc ggcgaggtcc cagtgctgtc agagcctggc 10320 cgagtcgggt gctggaggcg gggtgagttt gcattgcaaa tcgcgtccta ggccggggtg 10380 cggagtgagt cggctggagc gggcccctga gtcacggcgg gcaggttctg agcgtgcgcc 10440 ccgcccccgt cggcgcctct gagcggatcg aggcacccat gagttgagac tccaaaacta 10500 atcaagcaaa cgaaactgcc tactgcgcct tgggaggtgg ggcggtgtcc gtacacattg 10560 acacctttta tcttcttcac agctgcatcc ctgggtgact cctggtggac ctacctgctt 10620 ctagcccaag aaacctgggc ctatgcctta cccatgctgt ctagtgcagc ctgaccaaat 10680 gccaagtgct gactgacctc tgctcggcct ccacgccgcg gaatgacatc ttccatcttc 10740 cggaccttgc agcatcagga cttggaaatt tctcaggata aagattttta caatgacaat 10800 ctacttttta tcaattaact tgaactgttg taggactcta ctgaaaatat gaagaattat 10860 ttttatacaa aggatcctta agcttggagc acaataaaga tgacctctgt ccctcacccc 10920 cactgtctag aacttccaac ctggccaaag tgtggaccgg ttgggcctga ggcaagatgc 10980 ctggctgcac ccttcttcct cttctgaagc ctatactgac gctgatgttt ggccagtgtg 11040 ggaaccctgc tgttgcaaag tgtactattc tataaaagtt gtttttcatt ggtgtttgca 11100 gtgccttgta ccttctcaac cttgcatctg tctcaccctt gttccccagg tgcggtctaa 11160 gotggggtgg atagtactag cccagatttc tctcgagacc tgtattgcat gggtggatac 11220 aaaggtattg ggtgcctact ctagccatct ctccagagat ggaaaagcaa ttcagacacc 11280 taggaaggca aggtagctgt ctgtgagcct gtgtctgccc tccagggtgg ctctcccctg 11340 ggaaggatct gtgtaagagg ggcaagtgca gggtgctagg ctgaaggcag agctctggat 11400 tgtgggcatc tctaggccca gçrtotctctt ccttaccact tgggtggccc ttggcaaatt 11460 gccttatttg oaaatggtat tgagcttaaa gctccctccc aggttttgga taacctgccc 11520 atgagcttgc agccagtgtg tgotaggcac ccçrtgctgac tgctagggtc agtggccatc 11580 gtgaggccct gcagatagat ctttacttta agattctcta gtgagcaagg aagacctgga 11640 agcttcctca gtactcccca cacaagttcc ctagcctagg gagccaagct gtgattgcta 11700 agatattacc tggctcoacc tttgaccccc gagcctccga agctttgaag tctccgtgtg 11760 tccaaagctc ccttttattg caggggtttg ggaggggctg aggggatccc caggtggttt 11820 tagggtgctt caggcatccc ttcagaaggg agtggtcagg gcacaaccgt tggagctatg 11880 ggaatcagga agtgctgtgc aatggagcag atgccttcca ggtacctgtg gtggctatac 11940 agaaggcagt atacaagaag ctcaatctgt attatgatag ctgggctcct tccctgcagg 12000 acccagaacc ccaaaagcca gggtcaaagt tgaatctgta actttggccc cagcttgtca 12060 gcttctctga tgaaggtcag gctcagttgg ggtcaggcca agcacagctt ggagccacaa 12120 aactgagtgg acctgcctta gaggacaaaa tggggcatgg caaggccatt gagggagggc 12180 caccctcttc ccaggagccc gttgccagcc agtgtgttca ctgaactagg ggacctgaat 12240 tgtcccctga tttctttcct gtttcttaaa gtggcttatg gggaatggag gggttgctgg 12300 aagcgtgagc tcccttgtgt ccataaattc ccagtggtgt caatggtgtg cccctgttgt 12360 attatgggat atctctgaag tcttcattaa acaactttat tggctcacat ctgtaatctg 12420 aacacttagg agactgagat aggaggacag tccaagctca aaggggtagg gatgaggatg 12480 ggggctagga aggaggaaag gcagatggct cagtaggtga cagtgcttgc tgtgagagta 12540 taagggcccg cattgaactc ttcaaaaccc acagagaaat tggatattaa agcacatctg 12600 taatcccggt gctcctatgg aaagaaggga ggcagagaca gggggaatct tcaggaggta 12660 tccaagccag ctaggctggc acacacaacg gaaaaacaag agcctcctat gtcaaacaag 12720 gtggaaggtg aggaacaaca cttgatgttg tcctccgatc ttcatgcatg agtaggtgca 12780 tacacaaccc aggoacaaag gaacccttct gcttcaggaa otgagggtgt actgctgtgt 12840 ctgaaagaaa ctccaccctt agggaactta ctttctgctg gagatgagcc tattggcaag 12900 aggcatgtac cagcttcatg ggtaatcaag tgaaaagaaa ctgcttaaag cccaatagcc 12960 gggttgtggc ttaaggaggc tttctgcaac ttccaccctg ctgtcttcct ccacgtggtt 13020 ttgaagcatc tccagactgc acaatttcct tgcctaagga aaccctttat cacccatggt 13080 gatgaaagtg cagcttgcca gccagtggca ccgtttcttt tctgatgtat agaaccaggg 13140 tccatcccat gtctaaacac caaacttgca aggtctctta agcctcttgg aagcaatttg 13200 tcccagggat cacgtgccac acgaagcata gacaccacac ctgggagacc aatctcgggt 13260 ggatgccagc ttccagacag ataatgtgtc ctttgtatac cagtctaggg gctggccagg 13320 ctacagcaga agtctggaac tgtatccatc tgtctatata gtgctgacct cgtggggtag 13380 tcacgtgtcc tgtgataccc cagggttcag ctgagcttct aggttagtct gtcaatcaag 13440 gctatgttac tcaaggtgtc tttcattccc gggcagcacc attgaagaca caatactccc 13500 cagatactgt cttcccaaag gggcccaggc agtcctggga gcccagctat caatcagcct 13560 ttagagtccc agaaccctga gctctacagg gacatagaaa caatcctcct gctgcaatat 13620 gcaggctgtc cagggcagct tgagaaatgt ctgaggcaca gagcaaagca agtggagttt 13680 cagcaggttc ctgtccgtca tctttctttg gttttgagca gccttctcct gccatgtgtc 13740 cccatcatgc tggtggcccg aaacgtcaga gctcacagac tgattatttc aagtctttat 13800 attgtagtga caggaagccg gctgaggccc acgtcttact ctaaaagggc aaaggagtag 13860 ccgtgagagg atttaaaatg caaagcttct ctttctttgg tgctttctgt cctgcactca 13920 ctaatttaat gccattgtca ggaaaggagc catttaatgg cagttggttc tctatafccca 13980 aaggctctcc atccatagtt tgaaaaatgt ttgtgtgtgc atgcatgcat gtataagtat 14040 açrtacatgtg catgtgtgaa tgtgtggagg gcagaggctg acgttgggcg tcttcaatta 14100 ttctgcacct tagcttttga gacagggtct cactgggcct gaagctcatt tatagggtat 14160 attggctgcc tggaaagcct gggtttttat atgggtgcag aggtcaaact catgtgttca 14220 tgtttttgta gtacttaaat gtttgagcta tctttccagc ccattgaaaa tattttgaga 14280 tgtttgggta tggtggtgca aacctttaat ttcagcactc agaaggcagt ggcaggcgaa 14340 tctctgattt tcagatcagc ctggtttata gctctagttc caggacaacc agagctacaa 14400 agaaaacaaa atgacctcta aaaaacaaaa ccaaaacaaa atgttttaag aaacaatttt 14460 actcatcgta aacatgtggg gacctttccc ttgtcacata cagtgttctg ttgtcgtggt 14520 gcagggtcag tccctgcggg aggattaaag cacaggaggg tacatgtagg ctctgtaaca 14580 tactacagac ttcgacagaa gagttttgag aagtcctttt tggtatctca aaaaggtggt 14640 agtttcccaa atcggtcacc ctcaagtata aaagaccaac cagaataagt gggcatgcat 14700 gttgttgcca tctgtctttt ttgttgcata atgccagtta gacgtgcaaa tgccagaaca 14760 tttagctagc atacagaaac taagacagga catagttccc agtaccccag aggtacctca 14820 tggccaaagt ccagtagttt tcatagtgtg ccagtaotgt ccatccttgo ttactggtgg 14880 gaaagagaag gacaagacag gcttggtggc acatgctttt aaacccagca ctgagggtgg 14940 agtggggggg gcagggctct atgaatttta aggtcatcct gatctacata gtaagttcca 15000 ggtcaaccaa ggtgtcacag taagactgtg tctcaaacaa cagccacgac aaagagagac 15060 ttgggatgao cttgctctcc tgtcaatatc ttcagcataa gaagttgtcc gtttgatgta 15120 gggaagtctc tttccgagag atagatgtag tcccttgtcc cttaactctt catgcttact 15180 tcatctottt cctgcctttg aagccaagtt ctggtttgaa tgggaaatgt ggtccttgga 15240 cactgagctb gctcagctct gggtttaact agaagacttt atggtgtggg tggcaagact 15300 ggacacaaca gagcaacaab gtctccttat tgaacaagta tactccagag tctcctgacc 15360 ttcaccctcc cactaggggt caaaggtaag agtagcagga atttcaagat agggatactg 15420 tggggcccat ggggctgcag aggtctgatg cctaagaagc tggtcctcaa atcacccaca 15480 gaactgccgt gtgaagagac cccacatatc acttgcttcc tgcccctctt gagaccacag 15540 ccccttgtag acagtgacac ccaggcatgt ccagcagcag aagggatgtg acatggatca 15600 cttttgtcaa tggggccctg ttactcttac acaccctccc ttctcataag attggtgacc 15660 ttcagagacg tgggtaccaa agcagcacgt ctgtgtccag aagtaactgg cctgatgaca 15720 ggctgggcaa acctagtgtg gagtgaggct gaagggccct gatctagggc tgtcaagagc 15780 gaaggtaggg gctgtaggac agggagggcc ttggaggctt cacagcacag gtaggccctt 15840 gggtaggtgc atgttgccgc ctctgctctc ctgaaagagg ggtctggccc ggtgagtggc 15900 ttctcagatt cagtctgagt ggttggtttg gcttggctct gagttctgag ggcctgggaa 15960 tggctttctg ttctgaagcc tagaggagat gagagagagg aagaaaggat ccagaagctg 16020 attgtatggg gtctaggctg taagggcagg tgaetagggg agggtggagg atgctgccag 16080 ggagaagaca cagcacaaag acacagaaag ttccaacctc cccggggggc acatcctcct 16140 ggactcttta agggttttac cctatctaac agccataggt acccagagaa agactccatg 16200 tgaaoaggcc acacacccct tatgcctgcc tgaggcaggg actggatgtt tgctgttttc 16260 tgcttacgta gagggactgg tctgccagtt agagaggagc caggacccag ctcagacctc 16320 taggacactc taaccccttc caagcatgtg aggaaaaggc ccatgctctg agcctggaga 16380 ccagagccag gtgctcgggg ctcaggaagg actccctaaa aggccgactg gaagaggtaa 16440 ctctgccttg accaccaggc cctgcttcac ctcagatcc 16479

<210> 32 <211> 5616 <212> ADN <213> Homo sapiens <400> 32 ccccggcgca gcgcggccgc agcagcctcc gccccccgca cggtgtgagc gcccgacgcg 60 gccgaggcgg ccggagtccc gagctagccc cggcggccgc cgccgcccag accggacgac 120 aggccacctc gtcggcgtcc gcccgagtcc ccgcctcgcc gccaacgcca caaccaccgc 180 gcacggcccc ctgactccgt ccagtattga tcgggagagc cggagcgagc tcttcgggga 240 gcagogatgc gaccctccgg gacggccggg gcagcgctcc tggcgctgct ggctgcgctc 300 tgcccggcga gtcgggctct ggaggaaaag aaagtttgcc aaggcacgag taacaagctc 360 acgcagttgg gcacttttga agatcatttt ctcagcctcc agaggatgtt caataactgt 420 gaggtggtcc ttgggaattt ggaaattacc tatgtgcaga ggaattatga tctttccttc 480 ttaaagacca tccaggaggt ggctggttat gtcctcattg ccctcaacac agtggagcga 540 attcctttgg aaaacctgca gatcatcaga ggaaatatgt actacgaaaa ttcctatgcc 600 ttagcagtct tatctaacta tgatgcaaat aaaaccggac tgaaggagct gcccatgaga 660 aatttacagg aaatcctgca tggcgccgtg cggttcagca acaaccctgc cctgtgcaac 720 gtggagagca tccagtggcg ggacatagtc agcagtgact ttctcagcaa catgtcgatg 780 gacttccaga accacctggg cagctgccaa aagtgtgatc caagctgtcc caatgggagc 840 tgctggggtg caggagagga gaactgccag aaactgacca aaatcatctg tgcccagcag 900 tgctccgggc gctgccgtgg caagtccccc agtgactgct gccacaacca gtgtgctgca 960 ggctgcacag gcccccggga gagcgactgc ctggtctgcc gcaaattccg agacgaagcc 1020 acgtgcaagg acacctgccc cccactcatg ctctacaacc ccaccacgta ccagatggat 1080 gtgaaccccg agggcaaata cagctttggt gccacctgcg tgaagaagtg tccccgtaat 1140 tatgtggtga cagatcacgg ctcgtgcgtc cgagcctgtg gggccgacag ctatgagatg 1200 gaggaagacg gcgtccgcaa gtgtaagaag tgcgaagggc cttgccgcaa agtgtgtaac 1260 ggaataggba ttggtgaatt taaagactca ctctccataa atgctacgaa tattaaacac 1320 ttcaaaaact gcacctccat cagtggcgat ctccacatcc tgccggtggc atttaggggt 1380 gactccttca cacatactcc tcctctggat ccacaggaac tggatattct gaaaaccgta 1440 aaggaaatca cagggttttt gctgattcag gcttggcctg aaaacaggac ggacctccat 1500 gcctttgaga acctagaaat catacgcggc aggaccaagc aacatggtca gttttctctt 1560 gcagtcgtca gcctgaacat aacatccttg ggattacgct ccctcaagga gataagtgat 1620 ggagatgtga taatttcagg aaacaaaaat ttgtgctatg caaatacaat aaactggaaa 1680 aaactgtttg ggacctccgg tcagaaaacc aaaattataa gcaacagagg tgaaaacagc 1740 tgcaaggcca caggccaggt ctgccatgcc ttgtgctccc ccgagggctg ctggggcccg 1800 gagcccaggg actgcgtctc ttgccggaat gtcagccgag gcagggaatg cgtggacaag 1860 tgcaaccttc tggagggtga gccaagggag tttgtggaga actctgagtg catacagtgc 1920 cacccagagt gcctgcctca ggccatgaac atcacctgca caggacgggg accagacaac 1980 tgtatccagt gtgcccacta cattgacggc ccccactgcg tcaagacctg cccggcagga 2040 gtcatgggag aaaacaacac cctggtctgg aagtacgcag acgccggcca tgtgtgccac 2100 ctgtgccatc caaactgcac ctacggatgc actgggccag gtcttgaagg ctgtccaacg 2160 aatgggccta agatcccgtc catcgccact gggatggtgg gggccctcct cttgctgctg 2220 gtggtggccc tggggatcgg cctcttcatg cgaaggcgcc acatcgttcg gaagcgcacg 2280 ctgcggaggc tgctgcagga gagggagctt gtggagcctc ttacacccag tggagaagot 2340 cccaaccaag ctctcttgag gatcttgaag gaaactgaat tcaaaaagat caaagtgctg 2400 ggctccggtg cgttcggcac ggtgtataag ggactctgga tcccagaagg tgagaaagtt 2460 aaaattcccg tcgctatcaa ggaattaaga gaagcaacat ctccgaaagc caacaaggaa 2520 atcctcgatg aagcctacgt gatggccagc gtggacaacc cccacgtgtg ccgcotgotg 2580 ggcatctgcc tcacctccac cgtgcagctc atcacgcagc tcatgccctt cggctgcctc 2640 ctggactatg tccgggaaca caaagacaat attggctccc agtacctgct caactggtgt 2700 gtgcagatcg caaagggcat gaactacttg gaggaccgtc gcttggtgca ccgcgacctg 2760 gcagccagga acgtactggt gaaaacaccg cagcatgtca agatcacaga ttttgggctg 2820 gccaaactgc tgggtgcgga agagaaagaa taccatgcag aaggaggcaa agtgcctatc 2880 aagtggatgg cattggaatc aattttacac agaatctata cccaccagag tgatgtctgg 2940 agctacgggg tgaccgtttg ggagttgatg acctttggat ccaagccata tgacggaatc 3000 cctgccagcg agatctcctc catcctggag aaaggagaac gcctccctca gccacccata 3060 tgtaccatcg atgtctacat gatcatggtc aagtgctgga tgatagacgc agatagtcgc 3120 ccaaagttcc gtgagttgat catcgaattc tccaaaatgg cccgagaccc ccagcgctac 3180 cttgtcattc agggggatga aagaatgcat ttgccaagtc ctacagactc caacttctac 3240 cgtgccctga tggatgaaga agacatggac gacgtggtgg atgccgacga grtacctcatc 3300 coacagcagg gcttcttcag cagcccctcc acgtcacgga ctcccctoct gagctctctg 3360 agtgcaacca gcaacaattc caccgtggct tgcattgata gaaatgggct gcaaagctgt 3420 cccatcaagg aagacagctt cttgcagcga tacagctcag accccacagg cgccttgact 3480 gaggacagca tagacgacac cttcctccca gtgcctgaat acataaacca gtccgttccc 3540 aaaaggcccg ctggctctgt gcagaatcct gtctatcaca atcagcctct gaaccccgcg 3600 cccagcagag acccacacta ccaggacccc cacagcactg cagtgggcaa ccccgagtat 3660 ctcaacactg tccagcccac ctgtgtcaac agcacattcg acagccctgc ccactgggcc 3720 cagaaaggca gccaccaaat tagcctggac aaccctgact accagcagga cttctttccc 3780 aaggaagcca agccaaatgg catctttaag ggctccacag ctgaaaatgc agaataccta 3840 agggtcgcgc cacaaagcag tgaatttatt ggagcatgac cacggaggat agtatgagcc 3900 ctaaaaatco agactotttc gatacccagg accaagccac agcaggtcct ccatcccaac 3960 agccatgccc gcattagctc ttagacccac agactggttt tgcaacgttt acaccgacta 4020 gccaggaagt acttccacct cgggcacatt ttgggaagtt gcattccttt gtcttcaaac 4080 tgtgaagcat ttacagaaac gcatccagca agaatattgt ccctttgagc agaaatttat 4140 ctttcaaaga ggtatatttg aaaaaaaaaa aaagtatatg tgaggatttt tattgattgg 4200 ggatcttgga gtttttcatt gtcgctattg atttttactt caatgggctc ttccaacaag 4260 gaagaagctt gctggtagca cttgctaccc tgagttcatc caggcccaac tgtgagcaag 4320 gagcacaagc cacaagtctt ccagaggatg cttgattcca gtggttctgc ttcaaggctt 4380 ccactgcaaa acactaaaga tccaagaagg ccttcatggc cccagcaggc cggatcggta 4440 ctgtatcaag tcatggcagg tacagtagga taagccactc tgtcccttcc tgggcaaaga 4500 agaaacggag gggatggaat tcttccttag acttactttt gtaaaaatgt ccccacgçrta 4560 cttactcccc actgatggac cagtggtttc cagtcatgag cgttagactg acttgtttgt 4620 cttccattcc attgttttga aactcagtat gctgcccctg tcttgctgtc atgaaatcag 4680 caagagagga tgacacatca aataataact cggattccag cccacattgg attcatcagc 4740 atttggacca atagcccaca gctgagaatg tggaatacct aaggatagca ccgcttttgt 4800 tctcgcaaaa acgtatctcc taatttgagg ctcagatgaa atgcatcagg tcctttgggg 4860 catagatcag aagactacaa aaatgaagct gctctgaaat ctcctttagc catcacccca 4920 accccccaaa attagtttgt gttacttatg gaagatagtt ttctcctttt acttcacttc 4980 aaaagctttt tactcaaaga gtatatgttc cctccaggtc agctgccccc aaaccccctc 5040 cttacgcttt gtcacacaaa aagtgtctct gccttgagtc atctattcaa gcacttacag 5100 ctctggccac aacagggoat tttacaggtg cgaatgacag tagcattatg agtagtgtgg 5160 aattcaggta gtaaatatga aactagggtt tgaaattgat aatgctttca caacatttgc 5220 agatgtttta gaaggaaaaa agttccttcc taaaataatt tctctacaat tggaagattg 5280 gaagattcag ctagttagga gcccaccttt tttcctaatc tgtgtgtgcc ctgtaacctg 5340 actggttaac agcagtcctt tgtaaacagt gttttaaaot ctcctagtca atatccaccc 5400 catccaattt atcaaggaag aaatggttca gaaaatattt tcagcctaca gttatgttca 5460 gbcacacaca catacaaaat gttccttttg cttttaaagt aatttttgac tcccagatca 5520 gtcagagccc ctacagcatt gttaagaaag tatttgattt ttgtctcaat gaaaataaaa 5580 ctatattcat ttccactcta aaaaaaaaaa aaaaaa 5616

<210> 33 <211> 2156 <212> ADN <213> Homo sapiens <4Ο0> 33 cgggcccgtt goaagatggc ggcggccatg ctgggccccg gggctgtgtg tgcgcagcgg 60 gcggcggcgc ggcccggaag gctggcgcgg cgacggcgtt agcccggccc tcggcccctc 120 tttgcggccg ctccctccgc ctattccctc cttgctcgag atggatctgc ccgtgggccc 180 cggcgcggcg gggcccagca acgtcccggc cttcctgacc aagctgtgga ccctcgtgag 240 cgacccggac accgacgcgc tcatctgctg gagcccgagc gggaacagct tccacgtgtt 300 cgaccagggc cagtttgcca aggaggtgct gcccaagtac ttcaagcaca acaacatggc 360 cagcttcgtg cggcagctca acatgtatgg cttccggaaa gtggtccaca tcgagcaggg 420 cggcctggtc aagccagaga gagacgacac ggagttccag cacccatgct tcctgcgtgg 480 ccaggagcag ctccttgaga acatcaagag gaaagtgacc agtgtgtcca ccctgaagag 540 tgaagacata aagatccgcc aggacagcgt caccaagctg ctgacggacg tgcagctgat 600 gaaggggaag caggagtgca tggactccaa gctcctggcc atgaagcatg agaatgaggc 660 tctgtggcgg gaggtggcca gccttcggca gaagcatgcc cagcaacaga aagtcgtcaa 720 caagctcatt cagttcctga tctcactggt gcagtcaaac cggatcctgg gggtgaagag 780 aaagatcccc ctgatgctga acgacagtgg ctcagcacat tccatgccca agtatagccg 840 gcagttctcc ctggagcacg tccacggctc gggcccctac tcggccccct ccccagccta 900 cagcagctcc agcctctacg cccctgatgc tgtggccagc tctggaccca tcatctccga 960 catcaccgag ctggctcctg ccagccccat ggcctccccc ggcgggagca tagacgagag 1020 gcccctatcc agcagccccc tggtgcgtgt caaggaggag ccccccagcc cgcctcagag 1080 cccccgggta gaggaggcga gtcccgggcg cccatcttcc gtggacaccc tcttgtcccc 1140 gaccgccctc attgactcca tcctgcggga gagtgaacct gcccccgcct ccgtcacagc 1200 cctcacggac gccaggggcc acacggacac cgagggccgg cctccctccc ccccgcccac 1260 ctecacceet gaaaagtgcc teagcgtagc ctgcctggac aagaatgagc tcagtgacca 1320 cttggatgct atggactcca acctggataa cctgcagacc atgctgagca gccacggctt 1380 cagcgtggac accagtgccc tgctggacct gttcagcccc tcggtgaccg tgcccgacat 1440 gagcctgcct gaccttgaca gcagcctggc cagtatccaa gagctcctgt ctccccagga 1500 gccccccagg cctcccgagg cagagaacag cagcccggat tcagggaagc agctggtgca 1560 ctacacagcg cagccgctgt tcctgctgga ccccggctcc gtggacaccg ggagcaacga 1620 cctgccggtg ctgtttgagc tgggagaggg ctcctacttc tccgaagggg acggcttcgc 1680 cgaggacccc accatctccc tgctgacagg ctcggagcct cccaaagcca aggaccccac 1740 tgtctcctag aggccccgga ggagctgggc cagccgccca cccccacccc cagtgcaggg 1800 ctggtcttgg ggaggcaggg cagcctcgcg gtcttgggca ctggtgggtc ggccgccata 1860 gccccagtag gacaaacggg ctcgggtctg ggcagcacct ctggtcagga gggtcaccct 1920 ggcctgccag tctgccttcc cccaaccccg tgtcctgtgg tttggttggg gcttcacago 1980 cacacctgga ctgaccctgc aggttgttca tagtcagaat tgtattttgg atttttacac 2040 aactgtcccg ttccccgctc cacagagata cacagatata tacacacagt ggatggacgg 2100 acaagacagg cagagatcta taaacagaca ggctctaaaa aaaaaaaaaa aaaaaa 2156

<210> 34 <211> 2207 <212> ADN <213> Homo sapiens <400> 34 ctcttgaaga gggctggtat atttgtgcct gctggaggtg gaattaacag taagaaggag 60 aaagggattg aatggactta caggaaggat ttcaagtaaa ttcagggaaa cacatttact 120 tgaatagtac aacctagagt attattttac actaagacga cacaaaagat gttaaagtta 180 tcaccaagct gccggacaga tatatattcc aacaccaagg tgcagatcag catagatctg 240 tgattcagaa atcaggattt gttttggaaa gagctcaagg gttgagaaga actcaaaagc 300 aagtgaagat tactttggga actacagttt atcagaagat caacttttgc taattcaaat 360 accaaaggcc tgattatcat aaattcatat aggaatgcat aggtcatctg atcaaataat 420 attagccgtc ttctgctaca tcaatgcagc aaaaactctt aacaactgtg gataattgga 480 aatctgagtt tcagctttct tagaaataac tactcttgac atattccaaa atatttaaaa 540 taggacagga aaatcggtga ggatgttgtg ctcagaaatg tcactgtcat gaaaaatagg 600 taaatttgtt ttttcagcta ctgggaaact gtacctccta gaaccttagg tttttttttt 660 ttttaagagg acaagaagga ctaaaaatat caacttttgc ttttggacaa aaatgcatct 720 gactgtattt ttacttaagg gtattgtggg tttcctctgg agctgctggg ttctagtggg 780 ttatgcaaaa ggaggtttgg gagacaatca tgttcactcc agttttattt atagaagact 840 acggaaccac gaaagacggg aaatacaaag ggaaattctc tctatcttgg gtttgcctca 900 cagacccaga ccattttcac ctggaaaaca agcgtcctct gcacctctct ttatgctgga 960 tctctacaat gccatgacca atgaagaaaa tcctgaagag tcggagtact cagtaagggc 1020 atccttggoa gaagagacca gaggggcaag aaagggatac ccagcctctc ccaatgggta 1080 tcctcgtcgc atacagttat ctcggacgac tcctctgacc acccagagtc ctcctctagc 1140 cagcctccat gataecaact ttctgaatga tgctgacatg gtcatgagct ttgtcaaett 1200 agttgaaaga gacaaggatt tttctcacca gcgaaggcat tacaaagaat ttcgatttga 1260 tcttacccaa attcctcatg gagaggcagt gacagcagct gaattccgga tatacaagga 1320 ccggagcaac aaccgatttg aaaatgaaac aattaagatt agcatatatc aaatcatcaa 1380 ggaatacaca aatagggatg cagatctgtt cttgttagac acaagaaagg cccaagcttt 1440 agatgtgggt tggcttgtct ttgatatcac tgtgaccagc aatcattggg tgattaatcc 1500 ccagaataat ttgggcttac agctctgtgc agaaacaggg gatggacgca gtatcaacgt 1560 aaaatctgct ggtcttgtgg gaagacaggg acctcagtca aaacaaccat tcatggtggc 1620 cttcttcaag gcgagtgagg tacttcttcg atccgtgaga gcagccaaca aacgaaaaaa 1680 tcaaaaccgc aataaatcca gctctcatca ggactcctcc agaatgtcca gtgttggaga 1740 ttataacaca agtgagcaaa aacaagcctg taagaagcac gaactctatg tgagcttccg 1800 ggatctggga tggcaggact ggattatagc accagaagga tacgctgcat tttattgtga 1860 tggagaatgt tcttttccac ttaacgccoa tatgaatgcc accaaccacg ctatagttca 1920 gactctggtt catctgatgt ttcctgacca cgtaccaaag ccttgttgtg ctccaaccaa 1980 attaaatgcc atctctgttc tgtactttga tgacagctcc aatgtcattt tgaaaaaata 2040 tagaaatatg gtagtacgct catgtggctg ccactaatat taaataatat tgataataac 2100 aaaaagatct gtattaaggt ttatggctgc aataaaaagc atactttcag acaaacgggg 2160 aatttcctaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaa 2207

<210> 35 <211> 1878 <212> ADN <213> Homo sapiens <400> 35 gggcgcagcg gggcccgtct gcagcaagtg accgacggcc gggacggccg cctgccccct 60 ctgccacctg gggcggtgcg ggcccggagc ccggagcccg ggtagcgcgt agagccggcg 120 cgatgcacgt gcgctcactg cgagctgcgg cgccgcacag cttcgtggcg ctctgggcac 180 ccctgttcct gctgcgctcc gccctggccg acttcagcct ggacaacgag gtgcactcga 240 gcttcatcca ccggcgcctc cgcagccagg agcggcggga gatgcagcgc gagatcctct 300 ccattttggg cttgccccac cgcccgcgcc cgcacctcca gggcaagcac aactcggcac 360 ccatgttcat gctggacctg tacaacgcca tggcggtgga ggagggcggc gggcccggcg 420 gccagggctt ctcctacccc tacaaggccg tcttcagtac ccagggcccc cctctggcca 480 gcctgcaaga tagccatttc ctcaccgacg ccgacatggt catgagcttc gtcaacctcg 540 tggaacatga caaggaattc ttccacccac gctaccacca tcgagagttc cggtttgatc 600 tttccaagat cccagaaggg gaagctgtca cggcagccga attccggatc tacaaggact 660 acatccggga acgcttcgac aatgagacgt tccggatcag cgtttatcag gtgctccagg 720 agcacttggg cagggaatcg gatctcttcc tgotcgacag ccgtaccctc tgggcctcgg 780 aggagggctg gctggtgttt gacatcacag ccaccagcaa ccactgggtg gtcaatccgc 840 ggcacaacct gggcctgcag ctctcggtgg agacgctgga tgggcagagc atcaacccca 900 agttggcggg cctgattggg cggcacgggc cccagaacaa gcagcccttc atggtggctt 960 tcttcaaggc cacggaggtc cacttccgca gcatccggtc cacggggagc aaacagcgca 1020 gccagaaccg ctccaagacg cccaagaacc aggaagccct gcggatggcc aacgtggcag 1080 agaacagcag cagcgacoag aggcaggcct gtaagaagca cgagctgtat gtcagcttco 1140 gagacctggg c^ggcaggac fcggatcatcg cgcctgaagg ctacgccgcc tâctâctQtg 1200 agggggagtg tgccttccct ctgaactcct acatgaacgc caccaaccac gccatcgtgc 1260 agacgctggt ccacttcatc aacccggaaa cggtgcccaa gccctgctgt gcgcccacgc 1320 agctcaatgc catctccgtc ctctacttcg atgacagctc caacgtcatc ctgaagaaat 1380 acagaaacat ggtggtccgg gcctgtggct gccactagct cctccgagaa ttcagaccct 1440 ttggggccaa gtttttctgg atcctccatt gctcgccttg gccaggaacc agcagaccaa 1500 ctgccttttg tgagaccttc ccctccctat ccccaacttt aaaggtgtga gagtattagg 1560 aaacatgagc agcatatggc ttttgatcag tttttcagtg gcagcatcca atgaacaaga 1620 tcctacaagc tgtgcaggca aaacctagca ggaaaaaaaa acaacgcata aagaaaaatg 1680 gccgggccag gtcattggct gggaagtctc agccatgcac ggaetcgttt ccagaggtaa 1740 ttatgagcgc ctaccagcca ggccacccag ccgtgggagg aagggggcgt ggcaaggggt 1800 gggcacattg gtgtctgtgc gaaaggaaaa ttgacccgga agttcctgta ataaatgtca 1860 caataaaacg aatgaatg 1878

<210> 36 <211> 5434 <212> ADN <213> Homo sapiens <400> 36 cgtccgcgtg gggggggtgt gtgcccgcot tgcgcatgcg tgttccctgg gcatggccgg 60 ctccgttcca tccttctgca cagggtatcg cctctctccg tttggtacat cccctcctcc 120 cccacgcccg gactggggtg gtagacgcgc ctccgctcat cgcccctccc catcggtttc 180 cgcgcgaaaa gccggggcgc ctgcgctgcc gccgccgcgt ctgctgaagc ctccgagatg 240 ccggcgcgta ccgccccagc ccgggtgccc acactggccg tcccggccat ctogctgccc 300 gacgatgtcc gcaggcggct caaagatttg gaaagagaca gcttaacaga aaaggaatgt 360 gtgaaggaga aattgaatct cttgcacgaa tttctgcaaa cagaaataaa gaatcagtta 420 tgtgacttgg aaaccaaatt acgtaaagaa gaattatccg aggagggcta cctggctaaa 480 gtcaaatccc ttttaaataa agatttgtcc ttggagaacg gtgctcatgc ttacaaccgg 540 gaagbgaatg gacgtctaga aaacgggaac caagcaagaa gtgaagcccg tagagtggga 600 atggoagatg ccaacagccc ccccaaaccc ctttccaaac ctcgcacgcc caggaggagc 660 aagtccgatg gagaggctaa gcctgaacct tcacctagcc ccaggattac aaggaaaagc 720 accaggcaaa ccaccatcac atctcatttt gcaaagggcc ctgccaaacg gaaacctcag 780 gaagagtctg aaagagccaa atcggatgag tccatcaagg aagaagacaa agaccaggat 840 gagaagagac gtagagttac atccagagaa cgagttgcta gaccgcttcc tgcagaagaa 900 cctgaaagag caaaatcagg aacgcgcact gaaaaggaag aagaaagaga tgaaaaagaa 960 gaaaagagac tccgaagtca aaccaaagaa ccaacaccca aacagaaact gaaggaggag 1020 ccggacagag aagccagggc aggcgtgcag gctgacgagg acgaagatgg agacgagaaa 1080 gatgagaaga agcacagaag tcaacccaaa gatctagctg ccaaacggag gcccgaagaa 1140 aaagaacctg aaaaagtaaa tccacagatt tctgatgaaa aagacgagga tgaaaaggag 1200 gagaagagac gcaaaacgac ccccaaagaa ccaacggaga aaaaaatggc tcgcgccaaa 1260 acagtcatga actccaagac ccaccctccc aagtgcattc agtgcgggca gtacctggac 1320 gaccctgacc tcaaatatgg gcagcaccca ccagacgcgg tggatgagcc acagatgctg 1380 acaaatgaga agctgtccat ctttgatgcc aacgagtctg gctttgagag ttatgaggcg 1440 cttccccagc acaaactgac ctgcttcagt gtgtactgta agcacggtca cctgtgtccc 1500 atcgacaccg gcctcatcga gaagaatatc gaactcttct tttctggttc agcaaaacca 1560 atctatgatg atgacccgtc tcttgaaggt ggtgttaatg gcaaaaatct tggccccata 1620 aatgaatggt ggatcactgg ctttgatgga ggtgaaaagg ccctcatcgg cttcagcacc 1680 tcatttgccg aatacattct gatggatccc agtcccgagt atgcgcccat atttgggctg 1740 atgcaggaga agatctacat cagcaagatt gtggtggagt tcctgcagag caattccgac 1800 tcgacctatg aggacctgat caacaagatc gagaccacgg ttcctccttc tggcctcaac 1860 ttgaaccgct tcacagagga ctccctcctg cgacacgcgc agtttgtggt ggagcaggtg 1920 gagagttatg acgaggccgg ggacagtgat gagcagccca tcttcctgao gccctgcatg 1980 cgggacctga tcaagctggc tggggtcacg ctgggacaga ggcgagccca ggcgaggcgg 2040 cagaccatca ggcattctac cagggagaag gacaggggac ccacgaaagc caccaccacc 2100 aagctggtct accagatctt cgatactttc ttcgcagagc aaattgaaaa ggatgacaga 2160 gaagacaagg agaacgcctt taagcgccgg cgatgtggcg tctgtgaggt gtgtcagcag 2220 cctgagtgtg ggaaatgtaa agcctgcaag gacatggtta aatttggtgg cagtggacgg 2280 agcaagcagg cttgccaaga gcggaggtgt cccaatatgg ccatgaagga ggcagatgac 2340 gatgaggaag tcgatgataa catcccagag atgccgtcac ccaaaaaaat gcaccagggg 2400 aagaagaaga aacagaacaa gaatcgcatc tcttgggtcg gagaagccgt caagactgat 2460 gggaagaaga gttactataa gaaggtgtgc attgatgcgg aaaccctgga agtgggggac 2520 tgtgtctctg ttattccaga tgattcctca aaaccgctgt atctagcaag ggbcacggcg 2580 ctgtgggagg acagcagcaa cgggcagatg tttcacgccc actggttctg cgctgggaca 2640 gacacagtcc tcggggccac gtcggaccct ctggagctgt tcttggtgga tgaatgtgag 2700 gacatgcagc tttcatatat ccacagcaaa gtgaaagtca tctacaaagc cccctccgaa 2760 aactgggcca tggagggagg catggatccc gagtccctgc tggaggggga cgacgggaag 2820 acctacttct accagctgtg gtatgatcaa gactacgcga gattcgagtc ccctccaaaa 2880 acccagccaa cagaggacaa caagttcaaa ttctgtgtga gctgtgcccg tctggctgag 2940 atgaggcaaa aagaaatccc cagggtcctg gagcagctcg aggacctgga tagccgggtc 3000 ctctactact cagccaccaa gaacggcatc ctgtaccgag ttggtgatgg tgtgtacctg 3060 ccccctgagg ccttcacgtt caacatcaag ctgtccagtc ccgtgaaacg cccacggaag 3120 gagcccgtgg atgaggacct gtacccagag cactaccgga aatactccga ctacatcaaa 3180 ggcagcaacc tggatgcccc tgagccctac cgaattggcc ggatcaaaga gatcttctgt 3240 cccaagaaga gcaacggcag gcccaatgag actgacatca aaatccgggt caacaagttc 3300 tacaggcctg agaacaccca caagtccact ccagcgagct accacgcaga catcaacctg 3360 ctctactgga gcgacgagga ggccgtggtg gacttcaagg ctgtgcaggg ccgctgcacc 3420 gtggagtatg gggaggacct gcccgagtgc gtccaggtgt actccatggg cggccccaac 3480 cgcttctact tcctcgaggc ctataatgca aagagcaaaa gctttgaaga tcctcccaac 3540 catgcccgta gccctggaaa caaagggaag ggcaagggaa aagggaaggg caagcccaag 3600 tcccaagcct gtgagccgag cgagccagag atagagatca agctgcccaa gctgcggacc 3660 ctggatgtgt tttctggctg cggggggttg tcggagggat tccaccaagc aggcatctct 3720 gacacgctgt gggccatcga gatgtgggac cctgcggccc aggcgttccg gctgaacaac 3780 cccggctcca cagtgttcac agaggactgc aacatcctgc tgaagctggt catggctggg 3840 gagaccacca actcccgcgg ccagcggctg ccccagaagg gagacgtgga gatgctgtgc 3900 ggcgggccgc cctgccaggg cttcagcggc atgaaccgct tcaattcgcg cacctactcc 3960 aagttcaaaa actctctggt ggtttccttc ctcagctact gcgactacta ccggccccgg 4020 ttcttcctcc tggagaatgt caggaacttt gtctccttca agcgctccat ggtcctgaag 4080 ctcaccctcc gctgcctggt ccgcatgggc tatcagtgca ccttcggcgt gctgcaggcc 4140 ggtcagtacg gcgtggccca gactaggagg cgggccatca tcctggccgc ggcccctgga 4200 gagaagctcc ctctgttccc ggagccactg cacgtgtttg ctccccgggc ctgccagctg 4260 agcgtggtgg tggatgacaa gaagtttgtg agcaacataa ccaggttgag ctcgggtcct 4320 ttccggacca tcacggtgcg agacacgatg tccgacctgc cggaggtgcg gaatggagcc 4380 tcggcactgg agatctccta caacggggag cctcagtcct ggttccagag gcagctccgg 4440 ggcgcacagt accagcccat cctcagggac cacatctgta aggacatgag tgcattggtg 4500 gctgcccgca tgcggcacat ccccttggcc ccagggtcag actggcgcga tctgcccaac 4560 atcgaggtgc ggctctcaga cggcaccatg gccaggaagc tgcggtatac ccaccatgac 4620 aggaagaacg gccgcagcag ctctggggcc ctccgtgggg tctgctcctg cgtggaagcc 4680 ggcaaagcct gcgaccccgc agccaggcag ttcaacaccc tcatcccctg gtgcctgccc 4740 cacaccggga accggcacaa ccactgggct ggcctctatg gaaggctcga gtgggacggc 4800 ttcttcagca caaccgtcac caaccccgag cccatgggca agcagggccg cgtgctccac 4860 ccagagcagc accgtgtggt gagcgtgcgg gagtgtgccc gctcccaggg cttccctgac 4920 acctaccggc tcttcggcaa catcctggac aagcaccggc aggtgggcaa tgccgtgcca 4980 ccgcccctgg ccaaagccat tggcttggag atcaagcttt gtatgttggc caaagcccga 5040 gagagtgcct cagctaaaat aaaggaggag gaagctgcta aggactagtt ctgccctccc 5100 gtcacccctg tttctggcac caggaatccc caacatgcac tgatgttgtg tttttaacat 5160 gtcaatctgt ccgttcacat gtgtggtaca tggtgtttgt ggccttggct gacatgaagc 5220 tgttgtgtga ggttcgctta tcaactaatg atttagtgat caaattgtgc agtactttgt 5280 gcattctgga ttttaaaagt tttttattat gcattatatc aaatctacca ctgtatgagt 5340 ggaaattaag actttatgta gtttttatat gttgtaatat ttcttcaaat aaatctctcc 5400 tataaaccaa aaaaaaaaaa aaaaaaaaaa aaaa 5434

<210> 37 <211> 6082 <212> ADN <213> Homo sapiens <400> 37 ataacgtctt tgtcactaaa atgttcccca ggggccttcg gcgagtcttt ttgtttggtt 60 ttttgttttt aatctgtggc tcttgataat ttatctagtg gttgcctaca cctgaaaaac 120 aagacacagt gtttaactat caacgaaaga actggacggc tccccgccgo agtcccactc 180 cccgagtttg tggctggcat ttgggccacg ccgggctggg cggtcacagc gaggggcgcg 240 cagtttgggg tcacacagct ccgcttctag gccccaacca ccgttaaaag gggaagcccg 300 tgccccatca ggtccgctct tgctgagccc agagccatcc cgcgotctgc gggctgggag 360 gcccgggcca ggacgcgagt cctgcgcagc cgaggttccc cagcgccccc tgcagccgcg 420 cgtaggcaga gacggagccc ggccctgcgc ctccgcacca cgcccgggac cccacccagc 480 ggcccgtacc cggagaagca gcgcgagcac ccgaagctcc cggctggcgg cagaaaccgg 540 gagtggggcc gggcgagtgc gcggcatccc aggccggccc gaacgctccg cccgcggtgg 600 gccgacttcc cctcctcttc cctctctcct tcctttagcc cgctggcgcc ggacacgctg 660 cgcctcatct cttggggcgt tcttccccgt tggccaaccg tcgcatcccg tgcaactttg 720 gggtagtggc cgtttagtgt tgaatgttcc ccaccgagag cgcatggctt gggaagcgag 780 gcgcgaaccc ggcccccgaa gggccgccgt ccgggagacg gtgatgctgt tgctgtgcct 840 gggggtcccg accggccgcc cctacaacgt ggacactgag agcgcgctgc tttaccaggg 900 cccccacaac acgctgttcg gctactcggt cgtgctgcac agccacgggg cgaaccgatg 960 gctcctagtg ggtgcgccca ctgccaactg gctcgccaac gcttcagtga tcaatcccgg 1020 ggcgatttac agatgcagga tcggaaagaa tcccggccag acgtgcgaac agctccagct 1080 gggtagccct aatggagaac cttgtggaaa gacttgtttg gaagagagag acaatcagtg 1140 gttgggggtc acactttcca gacagccagg agaaaatgga tccatcgtga cttgtgggca 1200 tagatggaaa aatatatttt acataaagaa tgaaaataag ctccccactg gtggttgcta 1260 tggagtgccc cctgatttac gaacagaact gagtaaaaga atagctccgt gttatcaaga 1320 ttatgtgaaa aaatttggag aaaattttgc atcatgtcaa gctggaatat ccagttttta 1380 cacaaaggat ttaattgtga tgggggcccc aggatcatct tactggactg gctctctttt 1440 tgtctacaat ataactacaa ataaatacaa ggctttttta gacaaacaaa atcaagtaaa 1500 atttggaagt tatttaggat attcagtcgg agctggtcat tttcggagee agcatactac 1560 cgaagtagtc ggaggagctc ctcaacatga gcagattggt aaggcatata tattcagcat 1620 tgatgaaaaa gaactaaata tcttacatga aatgaaaggt. aaaaagcttg gatcgtactt 1680 tggagcttct gtctgtgctg tggacctcaa tgcagatggc ttctcagatc tgctcgtggg 1740 agcacccatg cagagcacca tcagagagga aggaagagtg tttgtgtaca tcaactctgg 1800 ctcgggagca gtaatgaatg caatggaaac aaacctcgtt ggaagtgaca aatatgctgc 1860 aagatttggg gaatctatag ttaatcttgg cgacattgac aatgatggct ttgaagatgt 1920 tgcbatcgga gctccacaag aagatgactt gcaaggtgct atttatattt acaatggccg 1980 tgcagatggg atctcgtcaa ccttctcaca gagaattgaa ggacttcaga tcagcaaatc 2040 gttaagtatg tttggacagt ctatatcagg acaaattgat gcagataata atggctatgt 2100 agatgtagca gttggtgctt ttcggtctga ttctgctgtc ttgctaagga caagacctgt 2160 agtaattgtt gacgcttctt taagccaccc tgagtcagta aatagaacga aatttgactg 2220 tgttgaaaat ggatggcctt ctgtgtgcat agatctaaca ctttgtttct catataaggg 2280 caaggaagtt ccaggttaca ttgttttgtt ttataacatg agtttggatg tgaacagaaa 2340 ggcagagtct ccaccaagat tctatttctc ttctaatgga acttctgacg tgattacagg 2400 aagcatacag gtgtccagca gagaagctaa ctgtagaaca catcaagcat ttatgcggaa 2460 agatgtgcgg gacatcctca ccccaattca gattgaagct gcttaccacc ttggtcctca 2520 tgtcatcagt aaacgaagta cagaggaatt cccaccactt cagccaattc ttcagcagaa 2580 gaaagaaaaa gacataatga aaaaaacaat aaactttgca aggttttgtg cccatgaaaa 2640 ttgttctgct gatttacagg tttctgcaaa gattgggttt ttgaagcccc atgaaaataa 2700 aacatatctt gctgttggga gtatgaagac attgatgttg aatgtgtcct tgtttaatgc 2760 tggagatgat gcatatgaaa cgactctaca tgtcaaacta cccgtgggtc tttatttcat 2820 taagatttta gagctggaag agaagcaaat aaactgtgaa gtcacagata actctggcgt 2880 ggtacaactt gactgcagta ttggctatat atatgtagat catctctcaa ggatagatat 2940 tagctttctc ctggatgtga gctcactcag cagagcggaa gaggacctca gtatcacagt 3000 gcatgctacc tgtgaaaatg aagaggaaat ggacaatcta aagcacagca gagtgactgt 3060 agcaatacct ttaaaatatg aggttaagct gactgttcat gggtttgtaa acccaacttc 3120 atttgtgtat ggatcaaatg atgaaaatga gcctgaaacg tgcatggtgg agaaaatgaa 3180 cttaactttc catgttatca acactggcaa tagtatggct cccaatgtta gtgtggaaat 3240 aatggtacca aattctttta gcccccaaac tgataagctg ttcaacattt tggatgtcca 3300 gactactact ggagaatgcc actttgaaaa ttatcaaaga gtgtgtgcat tagagcagca 3360 aaagagtgca atgcagacct tgaaaggcat agtccggttc ttgtccaaga ctgataagag 3420 gctattgrtac tgcataaaag ctgatccaca ttgtttaaat ttcttgtgta attttgggaa 3480 aatggaaagt ggaaaagaag ocagtgttca tatccaactg gaaggccggc catccatttt 3540 agaaatggat gagacttcag cactcaagtt tgaaataaga gcaacaggtt ttccagagcc 3600 aaatccaaga gtaattgaac taaacaagga tgagaatgtt gcgcatgttc tactggaagg 3660 actacatcat caaagaccca aacgttattt caccatagtg attatttcaa gtagcttgct 3720 acttggactt attgtacttc tgttgatctc atatgttatg tggaaggctg gcttctttaa 3780 aagacaatac aaatctatcc tacaagaaga aaacagaaga gacagttgga gttatatcaa 3840 cagtaaaagc aatgatgatt aaggacttct ttcaaattga gagaatggaa aacagactca 3900 ggttgtagta aagaaattta aaagacactg tttacaagaa aaaatgaatt ttgtttggac 3960 ttcttttact catgatcttg tgacatatta tgtcttcatg caaggggaaa atctcagcaa 4020 tgattactct ttgagataga agaactgcaa aggtaataat acagccaaag ataatctctc 4080 agcttttaaa tgggtagaga aacactaaag cattcaattt attcaagaaa agtaagccct 4140 tgaagatatc ttgaaatgaa agtataactg agttaaatta tactggagaa gtcttagact 4200 tgaaatacta cttaccatat gtgcttgcct cagtaaaatg aaccccactg ggtgggcaga 4260 ggttcatttc aaatacatct ttgatacttg ttcaaaatat gttctttaaa aatataattt 4320 tttagagagc tgttcccaaa ttttctaacg agtggaccat tatcacttta aagcccttta 4380 tttataatac atttcctacg ggctgtgttc caacaaccat tttttttcag cagactatga 4440 atattatagt attataggcc aaactggcaa acttcagact gaacatgtac actggtttga 4500 gcttagtgaa attacttctg gataattatt tttttataat tatggatttc accatctttc 4560 tttctgtata tatacatgtg tttttatgta ggtatatatt taccattctt cctatctatt 4620 cttcctataa cacaccttta tcaagcatac ccaggagtaa tcttcaaatc ttttgttata 4680 ttctgaaaca aaagattgtg agtgttgcac tttacctgat acacgctgat ttagaaaata 4740 cagaaaccat acctcactaa taactttaaa atcaaagctg tgcaaagact agggggccta 4800 tacttcatat gtattatgta ctatgtaaaa tattgactat cacacaacta tttccttgga 4860 tgtaattctt tgttaccctt tacaagtata agtgttacct tacatggaaa cgaagaaaca 4920 aaattcataa atttaaattc ataaatttag ctgaaagata ctgattcaat ttgtatacag 4980 tgaatataaa tgagacgaca gcaaaatttt catgaaatgt aaaatatttt tatagtttgt 5040 tcatactata tgaggttcta ttttaaatga ctttctggat tttaaaaaat ttctttaaat 5100 acaatcattt ttgtaatatt tattttatgc ttatgatcta gataattgca gaatatcatt 5160 ttatctgact ctgccttcat aagagagctg tggccgaatt ttgaacatct gttataggga 5220 gtgatcaaat tagaaggcaa tgtggaaaaa caattctggg aaagatttct ttatatgaag 5280 tccctgccac tagccagcca tcctaattga tgaaagttat ctgttcacag gcctgcagtg 5340 atggtgagga atgttctgag atttgcgaag gcatttgagt agtgaaatgt aagcacaaaa 5400 cctcctgaac ccagagtgtg tatacacagg aataaacttt atgacattta tgtattttta 5460 aaaaactttg tatcgttata aaaaggctag tcattctttc aggagaacat ctaggatcat 5520 agatgaaaaa tcaagccccg atttagaact gtcttctcca ggatggtctc taaggaaatt 5580 tacatttggt tctttcctac tcagaactac tcagaaacaa ctatatattt caggttatct 5640 gagcacagtg aaagcagagt actatggttg tccaacacag gcctctcaga tacaagggga 5700 acacaattac atattgggct agattttgcc cagttcaaaa tagtatttgt tatcaactta 5760 ctttgttact tgtatcatga attttaaaac cctaccactt taagaagaca gggatgggtt 5820 attctttttt ggcaggtagg ctatataact atgtgatttt gaaatttaac tgctctggat 5880 tagggagcag tgaatcaagg cagacttatg aaatctgtat tatatttgta acagaatata 5940 ggaaatttaa cataattgat gagctcaaat cctgaaaaat gaaagaatcc aaattatttc 6000 agaattatct aggttaaata ttgatgtatt atgatggttg caaagttttt ttgtgtgtcc 6060 aataaacaca ttgtaaaaaa aa 6082

<210> 38 <211> 2283 <212> ADN <213> Homo sapiens <400> 38 cggccgcgag ttgtgactgg agccacgatg cacggccagg cgcggtgaga agccagcccg 60 tagfcgcctcc cgaaggagcc cgggcgcagg gagggtcgcc ctgaggacac ggaggccgcc 120 aggcaggcca agggccgagg tgactgggct ggggcggtag ggaaggagcg agtgcgcctg 180 gctgcctccg cacggagttg tccctctctg ttttcgattg acacaaacac ttctccaaaa 240 gcggggaaac ctaagcaaca acagcaatca acaccaagat cttcctccta ccctcccctc 300 tttcccttct cccgcggtcg gccctcgccc cctcccccag gcccagcgcg ggcgctcggc 360 gcgtccagac ccgcggcgcg atgccggcag tttaggatcc aaagcttctc tgctcctttt 420 gttctttcct tccctttttt aaaaaaagag gggggaaatc ccagtggtgg gcagcctggc 480 acgcacacag tcgccctcat accccgacaa aagcagatgc actttgactt ctgacagctc 540 tacctcaagc cccggagaac tcagcggcgc tttcctcgca acccgagctc ggcgagtcgt 600 cgtcttcttc ttctccgttt ttatttattt atttccgttc ccgccgccgt tctcgctgac 660 cttcactcct ccgcgggctc tgagcagaag ggtcgcattc tctcccgcct gagacttctt 720 ttcctcgccc cgggagctca ggcggcgccg ctccagcccg gggccccggg actccccggc 780 tgcacacttc actgagacgc ccccccaggc cccgatcagc ctcgtttcct ccaccctact 840 ttgatttcct ggtgcgagtt ttggcttgca cggccgagtg tgtgtcctct ttttggagag 900 actggggagc tcgtgccgat tgtcttcagg agtcatcccc tgggctctac tttgcccctc 960 tctctctctg ggcctcatca gaccaaacca aagaccatgg ttcactgtgc cggctgcaaa 1020 aggcccatcc tggaccgctt tctcttgaac gtgctggaca gggcctggca cgtcaagtgc 1080 gtccagtgct gtgaatgtaa atgcaacctg accgagaagt gcttctccag ggaaggcaaa 1140 ctctactgca agaacgactt cttccggtgt ttcggtacca aatgcgcagg ctgcgctcag 1200 ggcatctccc ctagcgacct ggtgcggaga gcgcggagca aagtgtttca cctgaactgc 1260 tteacetgea tgatgtgtaa caagcagctc tccactggcg aggaactcta catcatcgac 1320 gagaataagt tcgtctgcaa agaggattac ctaagtaaca gcagtgttgc caaagagaac 1380 agccttcact cggccaccac gggcagtgac cccagtttgt ctccggattc ccaagacccg 1440 tcgcaggacg acgccaagga ctcggagagc gccaacgtgt cggacaagga agcgggbagc 1500 aacgagaatg acgaccagaa cctgggcgcc aagcggcggg gaccgcgcac caccatcaaa 1560 gccaagcagc tggagacgct gaaggccgcc ttcgctgcta cacccaagcc cacccgccac 1620 atccgcgagc agctggcgca ggagaccggc ctcaacatgc gcgtcattca ggtctggttc 1680 cagaaccggc gctccaagga gcggaggatg aagcagctga gcgccctggg cgcccggcgc 1740 cacgccttct tccgcagtcc gcgccggatg cggccgctgg tggaccgcct ggagccgggc 1800 gagctcatcc ccaatggtcc cttctccttc tacggagatt accagagcga gtactacggg 1860 cccgggggca actacgactt cttcccgcaa ggccccccgt cctcgcaggc ccagacacca 1920 gtggacctac ecttcgtgcc gtcatctggg ccgtccggga cgcccctggg tggcctggag 1980 cacccgctgc cgggccacca cccgtcgagc gaggcgcagc ggtttaccga catcctggcg 2040 cacccacccg gggactcgcc cagccccgag cccagcctgc ccgggcctct gcactccatg 2100 tcggccgagg tcttcggacc cagcccgccc ttctcgtcgc tgtcggtcaa cggtggggcg 2160 agctacggaa accacctgtc ccaccccccc gaaatgaacg aggcggccgt gtggtagcgg 2220 ggtctcgcac ggtctgcgga gttcgtggtt gtacagaaat gaacctttat ttaagaaaaa 2280 tag 2283

<210> 39 <211> 1485 <212> ADN <213> Homo sapiens <400> 39 tcctggagct gtgaggagat tcgggccgtc accctgcctc ccctgcgtcc cgccaccggc 60 cgcttctgtc ctcggaccca ttccaacaat ctcgtaaaac atggtggatt actatgaagt 120 tctaggcgtg cagagacatg cctcacccga ggatattaaa aaggcatatc ggaaactggc 180 actgaagtgg catccagata aaaatcctga gaataaagaa gaagcagaga gaaaattcaa 240 gcaagtagcg gaggcatatg aagtgctgtc ggatgctaag aaacgggaca tctatgacaa 300 atatggcaaa gaaggattaa atggtggagg aggaggtgga agtcattttg acagtccatt 360 tgaatttggc ttcacattcc gtaacccaga tgatgtcttc agggaatttt ttggtggaag 420 ggacccattt tcatttgact tctttgaaga cccttttgag gacttctttg ggaatcgaag 480 gggtccccga ggaagcagaa gccgagggac ggggtcgttt ttctctgcgt tcagtggatt 540 tccgtctttt ggaagtggat tttcttcttt tgatacagga tttacttcat ttgggtcact 600 aggtcacggg ggcctcactt cattctcttc cacgtcattt ggtggtagtg gcatgggcaa 660 cttcaaatcg atatcaactt caactaaaat ggttaatggc agaaaaatca ctacaaagag 720 aattgtcgag aacggtcaag aaagagtaga agttgaagaa gatggccagt taaagtcctt 780 aacaataaat ggtaaggagc agctgctgcg cttggataac aagtaattca acgcacgcac 840 ttaacagaaa tgttaaacta taacaagcac catttgagga ttaacaggaa catttttttg 900 aagatttcaa acgaactcga ctttcagtat aattgtacct aaagtattta taaacagctc 960 atcggagcct ctatttgtea tagacttttg agttgattgt tgggaccaca taataggacc 1020 attttttttt tgtctttaaa attgttgtaa atctctgtat gcactttgct tttttattaa 108Ò acgtactcca aggtgagtct tgactcttta gtgtaggaca agattgtaca ctaacaccag 1140 catggacctg cttttcattg tgtctgaaat grtgagccacg tagtgtcggc ctgctgtgaa 1200 gttaacattg ccaggacgat tcttctacag aaataatttc aatttttttc agtatttagt 1260 agtgaaagat attaatacat taatggtaat acatttctgg tttaatataa attaaggatg 1320 ttttctagtt gtgcatgaat gctggcaact tagtaagttt tgacaattgt ttaaatatgt 1380 aatgttaagc ttaggtttaa aaaagtaaag ctggtaaact gggtctttgt catttgcttt 1440 aaaaaaaaaa aaaaagaaaa taaatgcgaa tgtgttggtg cattc 1485

<210> 40 <211> 3538 <212> ADN <213> Rattus norvegicus <400> 40 ggtgcccaca gggcttgact agtgggattt gggggagcag tgggtgcagc gagcctggtc 60 cgttgactgc cagcagtaga caccggccgt gtgtggggga ggcggctagc tcagtggcct 120 tgggccgcgt ggcctggcgg tagaggagcc atggtttcta agttgagcca gctgcagacg 180 gagctcctgg ctgctctgct cgagtcgggc ctgagcaaag aggctctgat ccaggctctg 240 ggggagcccg ggccctacct gatggttgga gatggtcccc tggacaaggg ggagtcctgc 300 ggtgggactc gaggggacct gaccgagctg cccaatggcc tgggggagac gcgtggctcg 360 gaagatgaca cggatgacga tggggaagac ttcgcgccac ccattctgaa agagctggag 420 aacctcagcc cagaggaggc agcccaccag aaagccgtgg tggagtcact tcttcaggag 480 gacccatggc gcgtggcaaa gatggtcaag tcgtacctgc agcaacacaa catcccccag 540 cgggaggtgg tggacactac gggtctcaac cagtcccacc tgtcccagca cctcaacaag 600 ggcaccccca tgaagacgca gaagcgggcc gcgctgtaca cctggtacgt ccgcaagcag 660 cgagaggtgg ctcagcaatt cacccacgcg gggcagggcg gactgattga agagcccaca 720 ggtgatgagc tgccaaccaa aaaggggcgg aggaaccggt tcaagtgggg ccccgcatcc 780 cagcagatcc tgttccaggc ttacgagagg cagaagaacc ccagcaagga agagcgagag 840 accttggtgg aggagtgcaa tagggcggag tgcatccaga gaggggtgtc accatcgcag 900 gcccaggggc taggctccaa ccttgtcacc gaggtgcgtg tctacaactg gtttgccaac 960 cggcgcaagg aagaagcctt tcggcataag otggccatgg acacgtataa cgggcctcca 1020 cccgggccag gccccggccc tgcgctacct gcccacagtt ccccgggcct gcccacaacc 1080 accctctctc ccagtaaggt ccacggtgtg cggtatggac agtctgcaac cagcgaggca 1140 gctgaggtgc cctccagcag cggaggtccc ttagtcacag tgtctgcggc cttacaccaa 1200 gtgtccccca caggcttgga gcccagcagc ctgctgagca ccgaggccaa gctggtctca 1260 gccacggggg gtcccctgcc tcccgtcagc accctgacag cactgcacag cttggagcag 1320 acgtctccag gtctcaacca gcagccgcag aaccttatca tggcctcgct gcctggggtc 1380 atgaccatcg gcccagggga goccgcctcc ctgggtccca cgttcactaa cacgggtgcc 1440 tctaccctgg tcattggtct ggcctccaca caggcacaga gcgtgccagt catcaacagc 1500 atggggagca gcctgaccac cctgcagccg gtccagtttt cccagccact gcacccttcc 1560 tatcagcagc ctctcatgcc ccctgtacag agccacgtgg cccagagtcc cttcatggca 1620 accatggccc agctgcagag cccccacgcc ctgtacagcc acaagcctga ggtggcccag 1680 tacacgcata caagcctgct tccgcagacc atgctgatca cagacaccaa cctcagcacc 1740 cttgccagcc tcacgcccac caagcaggtc ttcacctcag acacagaggc ctccagtgag 1800 cctgggcttc atgagccgtc gtctccagcc acaaccattc acatccccag ccaggacccg 1860 tcaaacatcc agcacctgca gcctgctcac cggctcagca ccagtcccac agtgtcctcc 1920 agcagcctgg tgttgtacca gagttctgac tccaacgggc acagccacct gctgccatcc 1980 aaccacggtg tcatcgagac ttttatctcc acccagatgg cctcctcctc ccagtaacca 2040 tggtgactgc ctcccaggag ctgggctccc agagcctgca cagggggaga ggagggccac 2100 agccatgctg cctggagggt gttggagcct gccacctgcc acaggctgct ggccttccca 2160 gaactctatg ccttcatgct gcagctgctc ctccatcatc agaaagggat ggctctgagg 2220 tgtctcctca gcctgagggg caagcctcaa ggagccggag gacagcccaa tctggaccgc 2280 catccctgct ggttagaata gaaaacttaa tgcttggaac agaaggggga agcctgtatt 2340 gctggcaccc tccagtcaga gcttgcaggc cctgaaggat ctctgctgag ctcggaggcc 2400 ctacatcaac atggctgcca tctgtctcct gtgcctccca ggccactcca ccctgcgcca 2460 gagacccatg tgcctcttgg tgggttaccc tccctccaca ggatcttcca ggcagttctc 2520 tggctaggct tgggagceta gggagcaggg ctctcctagg ctttccccta ctaagtcgct 2580 cttcctcccg gccccaggac ctcatttgtt tccgtgaccg tatcttctga tgccagcttg 2640 gcatcttgcc tgcactagaa aggctgcttc agggctaaga ttgtcaccct tgttccttag 2700 ggcacgtaac tcatgccaag gtcacatcct aggcaatcac ctcctctggc tgcagggccc 2760 tacaacttcc ttcctggtgt gagagacgtg tagaactcgg aagacaaggc ctgagcaatg 2820 tctagtggag agagtgctga gaccagcaga gagaagccac ccaaggggct aggggctggc 2880 agctattctg atctctggcc tgctgcagag agcctggccc tcagtgggct cccccctcag 2940 cctggaaaga gccagcgccc cctgcagcct acggccggtc atgggcaagc ctagatgttt 3000 atttaacttt tagtaaagcc agtaagaagt gtgtagtagc ttcctgatta cctaggcatc 3060 tgtggccagg agggacggtg gagggaaggc agagggaagc agggtgaagg caggggcctg 3120 agctgtcggc aggctcatgg gatatgtgtt tacaoatctt tttgttcaac tggaaatgag 3180 gtgaggtgac tgcctggatt tetgtgtcct cctcggtact gcaagaaacc cacccagtcc 3240 aggtgtggtg ccattcccag agtcttaago tggggtgaca aagcgtatcc ggggtgtggg 3300 tggaaggatc ccactgtggt tttatgagao gtccccctaa cattgagcac agaggatgtg 3360 cctcggtggc acaatgcctg cctggtaagt gtaaagccac gggtttgatc cccggcactc 3420 aaacaacaac gcactgacag ctccttgtaa ctacgcagga ggcaaaccag gagactggcc 3480 aggttgagct acagagacac agacaaacaa taaacaaaaa gggttggtac tgaccagg 3538

<210> 41 <211> 3084 <212> ADN <213> Homo sapiens <400> 41 aagatctaaa aacggacatc tccaccgtgg gtggctcctt tttctttttc ttt.ttt.tccc 60 acccttcagg aagtggacgt ttcgttatct tctgatcctt gcaccttctt ttggggaaac 120 ggggcccttc tgcccagatc ccctctcttt tctcggaaaa caaactacta agtcggcatc 180 cggggtaact acagtggaga gggtttccgc ggagacgcgc cgccggaccc tcctctgcac 240 tttggggagg cgtgctccct ccagaaccgg cgttctccgc gcgcaaatcc cggcgacgcg 300 gggtcgcggg gtggccgccg gggcagcctc gtctagcgcg cgccgcgcag acgcccccgg 360 agbcgccagc taccgcagcc ctcgccgccc agtgcccttc ggcctcgggg cgggcgcctg 420 cgtcggtctc cgcgaagcgg gaaagcgcgg cggccgccgg gattcgggcg ccgcggcagc 480 tgctccggct gccggccggc ggccccgcgc tcgcccgccc cgcttccgcc cgctgtcctg 540 ctgcacgaac ccttccaact ctcctttcct cccccaccct tgagttaccc ctctgtcttt 600 cctgctgttg cgcgggtgct cccacagcgg agcggagatt acagagccgc cgggatgccc 660 caactctccg gaggaggtgg cggcggcggg ggggacccgg aactctgcgc cacggacgag 720 atgatcccct tcaaggacga gggcgatcct cagaaggaaa agatcttcgc cgagatcagt 780 catcccgaag aggaaggcga tttagctgac atcaagtctt ccttggtgaa cgagtctgaa 840 atcatcccgg ccagcaacgg acacgaggtg gccagacaag cacaaacctc tcaggagccc 900 taccacgaca aggccagaga acaccccgat gacggaaagc atccagatgg aggcctctac 960 aacaagggac cctcctactc gagttattcc gggtacataa tgatgccaaa tatgaataac 1020 gacccataca tgtcaaatgg atctctttct ccacccatcc cgagaacatc aaataaagtg 1080 cccgtggtgc agccatccca tgcggtccat cctctcaccc ccctcatcac ttacagtgac 1140 gagcactttt ctccaggatc acacccgtca cacatcccat cagatgtcaa ctccaaacaa 1200 ggcatgtcca gacatcctcc agctcctgat atccctactt tttatccctt gtctccgggt 1260 ggtgttggac agatcacccc acctcttggc tggcaaggtc agcctgtata tcccatcacg 1320 ggtggattca ggcaacccta cccatccfcca ctgtcagtcg acacttccat gtccaggttt 1380 tcccatcata tgattcoogg tootcctggt ccccacacaa otggcatocc tcatccagot 1440 attgtaacac ctoaggtcaa acaggaacat ccccacactg acagtgacct aatgcacgtg 1500 aagcctcagc atgaacagag aaaggagcag gagccaaaaa gacctcacat taagaagcct 1560 ctgaatgctt ttatgttata catgaaagaa atgagagcga atgtcgttgc tgagtgtact 1620 ctaaaagaaa gtgcagctat caaccagatt cttggcagaa ggtggcatgc cctctcccgt 1680 gaagagcagg ctaaatatta tgaattagca cggaaagaaa gacagctaca tatgcagctt 1740 tatccaggct ggtctgcaag agacaattat ggtaagaaaa agaagaggaa gagagagaaa 1800 ctacaggaat ctgcatcagg tacaggtcca agaatgacag ctgcctacat ctgaaacatg 1860 gtggaaaacg aagctcattc ccaacgtgca aagccaaggc agcgacccca ggacctcttc 1920 tggagatgga agcttgttga aaacccagac tgtctccacg gcctgcccag tcgacgccaa 1980 aggaacactg acatcaattt taccctgagg tcactgctag agacgctgat ccataaagac 2040 aatcactgcc aacccctctt tcgtctactg caagagccaa gttccaaaat aaagcataaa 2100 aaggtttttt aaaaggaaat gtaaaagcac atgagaatgc tagcaggctg tggggcagct 2160 gagcagcttt tctcccccca tatctgcgtg cacttcccag agcatcttgc atccaaacct 2220 gtaacctttc ggcaaggacg gtaacttggc tgcatttgcc tçrtcatgcgc aactggagcc 2280 agcaaccagc tatccatcag caccccagtg gaggagttca tggaagagtt ccctctttgt 2340 ttctgcttca tttttctfctc ttttcttttc tcctaaagct tttatttaac agtgcaaaag 2400 gatcgttttt ttttgctttt ttaaacttga atttttttaa tttacacttt ttagttttaa 2460 ttttcttgta tattttgcta gctatgagct tttaaataaa attgaaagtt ctggaaaagt 2520 ttgaaataat gacataaaaa gaagccttct ttttctgaga cagcttgtct ggtaagtggc 2580 ttctctgtga attgcctgta acacatagtg gcttctccgc ccttgtaagg tgttcagtag 2640 agctaaataa atgtaatagc caaaccccac tctgttggta gcaattggca gccctatttc 2700 agtttatttt ttcttctgtt ttcttctttt ctttttttaa acagtaaacc ttaacagatg 2760 cgttcagcag actggtttgc agtgaatttt catttctttc cttatcaccc ccttgttgta 2820 aaaagcccag cacttgaatt gttattactt taaatgttct gtatttgtat ctgtttttat 2880 tagccaatta gtgggatttt atgccagttg ttaaaatgag cattgatgrta cccatttttt 2940 aaaaaagcaa gcacagcctt tgcccaaaac tgtcatccta acgtttgtca ttccagtttg 3000 agttaatgtg ctgagcattt ttttaaaaga agctttgtaa taaaacattt ttaaaaattg 3060 tcatttaaaa aaaaaaaaaa aaaa 3084

<210> 42 <211> 2108 <212> ADN <213> Strongylocentrotus purpuratus <400> 42 gggaccgcct cggaggcaga agagccgcga ggagccagcg gagcaccgcg ggctggggcg 60 cagccacccg ccgctcctcg agtcccctcg cccctttccc ttcgtgcccc ccggcagcct 120 ccagcgtcgg tccccaggca gcatggtgag gtctgctccc ggaccctcgc caccatgtac 180 gtgagctacc tcctggacaa ggacgtgagc atgtacccta gctccgtgcg ccactctggc 240 ggcctcaacc tggcgccgca gaacttcgtc agccccccgc agtacccgga ctacggcggt 300 taccacgtgg cggccgcagc tgcagcggca gcgaacttgg acagcgcgca gtccccgggg 360 ccatcctggc cggcagcgta tggcgcccca ctccgggagg actggaatgg otacgcgcco 420 ggaggcgçcg cggccgccgc caacgccgtg gctcacggcc tcaacggtgg ctccccggcc 480 gcagccatgg gctacagcag ccccgcagac taccatccgc accaccaccc gcatcaccac 540 ccgcaccacc cggccgccgc gccttcctgc gcttctgggc tgctgcaaac gctcaacccc 600 ggccctcctg ggcccgccgc caccgctgcc gccgagcagc tgtctcccgg cggccagcgg 660 cggaacctgt gcgagtggat gcggaagccg gcgcagcagt ccctcggcag ccaagtgaaa 720 accaggacga aagacaaata tcgagtggtg tacacggacc accagcggct ggagctggag 780 aaggagtttc actacagtcg ctacatcacc atccggagga aagccgagct agccgccacg 840 ctggggctct ctgagaggca ggttaaaatc tggtttcaga accgcagagc aaaggagagg 900 aaaatcaaca agaagaagtt gcagcagcaa cagcagcagc agccaccaca gccgcctccg 960 ccgccaccac agcctcccca gcctcagcca ggtcctctga gaagtgtccc agagcccttg 1020 agtccggtgt cttccctgca agcctcagtg tctggctctg tccctggggt tctggggcca 1080 actggggggg tgctaaaccc caccgtcacc cagtgaccca ccggggtctg cagcggcaga 1140 gcaattccag gctgagccat gaggagcgtg gactctgcta gactcctcag gagagacccc 1200 tcccctccca cccacagcca tagacctaca gacctggctc tcagaggaaa aatgggagcc 1260 aggagtaaga caagtgggat ttggggcctc aagaaatata ctctcccaga tttttacttt 1320 ttcccatctg gctttttctg ccactgagga gacagaaagc ctccgctggg cttcattccg 1380 gactggcaga agcattgcct ggactgacca caccaaccag gccttcatcc tcctccccag 1440 ctcttctctt cctagatctg caggctacac ctctggctag agccgagggg agagagggac 1500 tcaagggaaa ggcaagcttg aggccaagat ggctgctgcc tgctcatggc cctcggaggt 1560 ccagctgggc ctcctgcctc cgggcaggca aggtttacac tgcggaagcc aaaggcagct 1620 aagatagaaa gctggactga ccaaagactg cagaaccccc aggtggcctg cgtctttttt 1680 ctcttccctt cccagaccag gaaaggcttg gctggtgtat gcacagggtg tggtatgagg 1740 gggtggttat tggactccag gcctgaccag ggggcccgaa cagggacttg tttagagagc 1800 ctgtcaccag agcttctctg ggctgaatgt atgtcagtgc tataaatgcc agagccaacc 1860 tggacttcct gtcattttca caatcttggg gctgatgaag aagggggtgg ggggagtttg 1920 tgttgttgtt gctgctgttt gggttgttgg tctgtgtaac atccaagcca gagtttttaa 1980 agccttctgg atccatgggg ggagaagtga tatggtgaag ggaagtgggg agtatttgaa 2040 cacagttgaa ttttttctaa aaagaaaaag agataaatga gctttccaga aaaaaaaaaa 2100 aaaaaaaa 2108 <210> 43 <211> 2756

<212> ADN <213> Homo sapiens <400> 43 atgoagttag gggagcagct cttggtgagc tcagtgaacc tgcctggcgc gcacttctac 60 ccgctggaga gtgcgcgagg cggcagcggc gggagcgctg gccacctccc cagcgcggcc 120 ccctotccto agaagttgga cttagacaaa gcgtccaaga agttttccgg cagtctctcc 180 tgcgaggcgg tgagcgggga gcccgoagcc gccagcgcag gggcccccgc ggccatgctt 240 agtgacaccg acgccgggga cgcatttgcc agcgctgcgg cagtggccaa gccggggccc 300 ccggacggcc gcaagggctc cccctgcggg gaggaggagc tgccctccgc cgctgcagcc 360 gccgccgccg ccgccgccgc ggctgcggcc actgcgcgct actccatgga cagcctgagc 420 tccgagcggt actacctcca gtcccccggt cctcaggggt cggagctggc tgcgccctgc 480 tcactcttcc cgtaccaggc ggcggctggg gcgccccacg gacctgtgta cccggctcct 540 aacggggcgc gctaccccta cggctccatg ctgccccccg gcggcttccc cgcggctgtg 600 tgcccacccg ggagggcgca gttcggccca ggagccggtg cgggcagtgg cgcgggcggt 660 agcagcggcg ggggcggcgg cccgggcacc tatcagtaca gccagggggc tccgctctac 720 gggccgtacc ctggagccgc agcggcggga tcttgcggag gactgggggg cctgggggtt 780 ccaggttctg gcttccgtgc ccacgtctac ctgtgcaacc ggcctctgtg gctcaaattc 840 caccgccacc aaactgagat gatcattacg aaacagggca ggcgcatgtt tcctttcttg 900 agcttcaaca taaacggact caatcccact gcccactaca atgtgttcgt agaggtggtg 960 ctggcggacc ccaaccactg gcgcttccag gggggcaaat gggtgacctg tggcaaagcc 1020 gacaataaca tgcagggcaa caaaatgtat gttcacccag agtctcctaa tactggttcc 1080 cactggatga gacaggagat ttcattcggg aaattaaaac tcaccaataa caaaggcgca 1140 aataacaaca acacccagat gatagtctta caatccttac acaaatacca acccogactg 1200 catattgttg aagttacaga ggatggcgtg gaggacttga atgagccctc aaagacccag 1260 acttttacct tctcagaaac gcaattcatt gcagtgactg cctaccaaaa caccgatatt 1320 actcaactaa agattgatca taaccccttt gcaaaaggct tcagagacaa ctatgattca 1380 toccatcaga ttgtccctgg aggtcggtac ggcgttcaat ccttottccc ggagcccttt 1440 gtcaacactt tacctcaagc ccgctattat aatggcgaga gaaccgtgcc acagaccaac 1500 ggcctccttt caccccaaca gagcgaagag gtggccaacc ctccccagcg gtggcttgtc 1560 acgcctgtcc agcaacctgg gaccaacaaa ctagacatca gttcctatga atctgaatat 1620 acttctagca cattgctccc atatggcatt aaatccttgc cccttcagac atcccatgcc 1680 ctggggtatt acccagaccc aacctttcct gcaatggcag ggtggggagg tcgaggttct 1740 taccagagga agatggcagc tggactacca tggacctcca gaacaagccc cactgtgttc 1800 tctgaagatc agctctccaa ggagaaagtg aaagaggaaa ttggctcttc ttggatagag 1860 acaccccctt ccatcaaatc tctagattcc aatgattcag gagtatacac cagtgcttgt 1920 aagcgaaggc ggctgtctcc tagcaactcc agtaatgaaa attcaccctc cataaagtgt 1980 gaggacatta atgctgaaga gtatagtaaa gacacctcaa aaggcatggg agggtattat 2040 gctttttaca caactcccta aagagttatt ttaacctcaa aaattagcta actttttgca 2100 gatggacttg gtggtgtttt ttgttgtctt ctttgcctag gttgccaaaa agatgtttgc 2160 cttccacctt gatgcatcct gttttgtgca attctctaaa agaaggtgcc aaagcttttt 2220 gattgctgca ggtaactgaa acaaacctag catttttaaa aaataagatt aatggaagac 2280 tttaaggtat tttaaaattc gaagggtatc caaggttctg tatttattta ttggggagac 2340 actaaccctt caaagaagca ggctgtgaac attgggtgcc cagtgctatc agatgagtta 2400 aaacctttga ttctcatttc tatttgtaaa ttcttaagca aatagaagcc gagtgttaag 2460 gtgttttgct tctgaaagag ggctgtgcct tccgtttcag aaggagacat tttgctgtta 2520 cattctgcca ggggcaaaag atactaggcc caggagtcaa gaaaagcttt tgtgaaagtg 2580 atagtttcac ctgactttga ttccttaacc cccggctttt ggaacaagcc atgtttgccc 2640 tagtccagga ttgcctcact tgagacttgc taggcctctg ctgtgtgctg gggtggccag 2700 tgggactcag gagagagcaa gctaaggagt caccaaaaaa aaaaaaaaaa aaaaaa 2756

<210> 44 <211> 1219 <212> ADN <213> Homo sapiens <400> 44 gggagcgggc gagtaggagg gggcgccggg ctatatatat agcggcctcg gcctcgggcg 60 ggcctggcgc tcagggaggc gcgcactgct cctcagagtc ccagctccag ccgcgcgctt 120 tccgcccggc tcgccgctcc atgcagccgg ggtagagccc ggcgcccggg ggccccgtcg 180 cttgcctccc gcacctcctc ggttgcgcac tcccgcccga ggtcggccgt gcgctcccgc 240 gggacgccac aggcgcagct ctgcccccca gcttcccggg cgcactgacc gcctgaccga 300 cgcacgccct cgggccggga tgtcggggcc cgggacggcc gcggtagcgc tgctcccggc 360 ggtcctgctg gccttgctgg cgccctgggc gggccgaggg ggcgccgccg cacccactgc 420 acccaacggc acgctggagg ccgagctgga gcgccgotgg gagagcctgg tggcgctctc 480 gttggcgcgc ctgccggtgg cagcgcagcc caaggaggcg gccgtccaga gcggcgccgg 540 cgactacctg ctgggcatca agcggctgcg gcggctctac tgcaacgtgg gcatcggctt 600 ccacctccag gcgctccccg acggccgcat cggcggcgcg cacgcggaca cccgcgacag 660 cctgctggag ctctcgcccg tggagcgggg cgtggtgagc atcttcggcg tggccagccg 720 gttcttcgtg gccatgagca gcaagggcaa gctctatggc tcgcccttct tcaccgatga 780 gtgcacgttc aaggagattc tccttcccaa caactacaac gcctacgagt cctacaagta 840 ccccggcatg ttcatcgccc tgagcaagaa tgggaagacc aagaagggga accgagtgtc 900 gcccaccatg aaggtcaccc acttcctccc caggctgtga ccctccagag gacccttgcc 960 tcagcctcgg gaagcccctg ggagggcagt gcgagggtca ccttggtgca ctttcttcgg 1020 atgaagagtt taatgcaaga gtaggtgtaa gatatttaaa ttaattattt aaatgtgtat 1080 atattgccac caaattattt atagttctgc gggtgtgttt tttaattttc tggggggaaa 1140 aaaagacaaa acaaaaaacc aactctgact tttctggtgc aacagtggag aatcttacca 1200 ttggatttct ttaacttgt 1219

<210> 45 <211> 2193 <212> ADN <213> Homo sapiens <400> 45 cgggagccca tggagcactg tcctcagaga tgcgcaggtt aggctcactg tctaggccag 60 gcccacctta gtcactgtgg actggcaatg gaagctcttc ctggacacac ctgccctagc 120 cctcaccctg gggtggaaga gaaatgagct tggcttgcaa ctcagaccat tccacggagg 180 catcctccct tccctgggct ggtgaataaa agtttcctga ggtcaaggac ttccttttcc 240 ctgccaaaat ggtgtccaga acttbgaggc cagaggtgat ccagtgattt gggagctgca 300 ggtcacacag gctgctcaga gggctgctga acaggatgtc ctcggacgac aggcacctgg 360 gctcoagctg cggctccttc atcaagactg agccgtccag cccgtcctcg ggcattgatg 420 ccctcagcca ccacagcccc agtggctcgt ccgacgccag cggcggcttt ggcctggccc 480 tgggcaccca cgccaacggt ctggactcgc cacccatgtt tgcaggcgcc gggctgggag 540 gcaccccatg ccgcaagagc tacgaggact gtgccagcgg catcatggag gactcggcca €00 tcaagtgcga gtacatgctc aacgccatcc ccaagcgcct gtgootcgtg tgcggggaca 660 ttgcctctgg ctaccactac ggcgtggcct cctgcgaggc ttgcaaggcc ttcttcaaga 720 ggacbatcca agggaacatt gagtacagct gcccggccac caacgagtgc gagatcacca 780 aacggaggcg caagtcctgc caggcctgcc gcttcatgaa atgcctcaaa gtggggatgc 840 tgaaggaagg tgtgcgcctt gatcgagtgc gtggaggccg tcagaaatac aagcgacggc 900 tggactcaga gagcagccca tacctgagct tacaaatttc tccacctgct aaaaagccat 960 tgaccaagat tgtctcatac ctactggtgg ctgagccgga caagctctat gccatgcctc 1020 cccctggtat gcctgagggg gacatcaagg ccctgaccac tctctgtgac ctggcagacc 1080 gagagcttgt ggtcatcatt ggctgggcca agcacatccc aggcttctca agcctctccc 1140 tgggggacca gatgagcctg ctgcagagtg cctggatgga aatcctcatc ctgggcatcg 1200 tgtaccgctc gctgccctat gacgacaagc tggtgtacgc tgaggactac atcatggatg 1260 aggagcactc ccgcctcgcg gggctgctgg agctctaccg ggccatcctg cagctggtac 1320 gcaggtacaa gaagctcaag gtggagaagg aggagtttgt gacgctcaag gccctggccc 1380 tcgccaactc cgattccatg fcacatcgagg atctagaggc tgtccagaag ctgcaggacc 1440 tgctgcacga ggcactgcag gactacgagc tgagccagcg ccatgaggag ccetggagga 1500 cgggcaagct gctgctgaca ctgccgctgc tgcggcagac ggccgccaag gccgtgcagc 1560 acfctctatag cgtcaaactg cagggcaaag tgcccatgca caaactcttc ctggagatgc 1620 tggaggccaa ggcctgggcc agggctgact cccttcagga gtggaggcca ctggagcaag 1680 tgccctctcc cctccaccga gccaccaaga ggcagcatgt gcatttccta actcccttgc 1740 ccoctccccc atctgtggcc tgggtgggca ctgctcaggc tggataccac ctggaggttt 1800 tccttccgca gagggcaggt tggccaagag cagcttagag gatctcccaa ggatgaaaga 1860 atgtcaagcc atgatggaaa atgccccttc caatcagctg ccttcacaag cagggatcag 1920 agcaactccc cggggatccc caatccacgc ccttctagtc caacccccct caatgagaga 1980 ggcaggcaga tctcacccag cactaggaca ccaggaggcc agggaaagca tctctggctc 2040 accatgtaac atctggcttg gagcaagtgg gtçrttctgca caccaggcag ctgcacctca 2100 ctggatctag tgttgctgcg agtgacctca cttcagagcc cctctagcag agtggggcgg 2160 aagtcctgat ggttggtgtc catgaggtgg aag 2193

<210> 46 <211> 1750 <212> ADN <213> Homo sapiens <400> 46 gcggtcttat ataagccaga tccgcagggg agtccgcaga agggttaaac aggtctttgg 60 gcttcggcga cctcgcccgc ggcagaaacc ggtaagaaga cagtgggctg cgcgtctcat 120 tttcagcctt gcceggactc tcccaaagec ggcgcecagt agtggctcca gagcccacag 180 gtggcccccg gcagtctctg gggcgcatgg agcggcgtta atagggctgg cggcgcaggc 240 cagtagccgc tccaacatga acctcgtggg cagctacgca caccatcacc accatcacca 300 cccgcaccct gcgcacccca tgctccacga acccttcctc ttcggtccgg cctcgcgctg 360 tcatcaggaa aggccctact tccagagctg gctgctgagc ccggctgacg ctgccccgga 420 cttccctgcg ggcgggccgc cgcccgcggc cgctgcagcc gccaccgcct atggtcctga 480 cgccaggcct gggcagagcc ccgggcggct ggaggcgctt ggcggccgtc ttggccggcg 540 gaaaggctca ggacccaaga aggagcggag acgcactgag agcattaaca gcgcattcgc 600 ggagttgcgc gagtgcatcc ccaacgtgcc ggccgacacc aagctctcca agatcaagac 660 tctgcgccta gccaccagct acatcgccta cctgatggac gtgctggcca aggatgcaca 720 gtctggcgat cccgaggcct tcaaggctga actcaagaag gcggatggcg gccgtgagag 780 caagcggaaa agggagctgc agcagcacga aggttttcct cctgccctgg gcccagtcga 840 gaagaggatt aaaggacgca ccggctggcc gcagcaagtc tgggcgctgg agttaaacca 900 gtgagccgag gcccgcgccg aggacctggc caggccagcc actcctgaag ccccgggagg 960 agaggaaggc agcggcgaac gccaggctct gggctccggc gactggtgct acgcatcccg 1020 cggagcttct gctgagcgcc ggcaggtcgt cggctgcaac cacacacttg gatcgcacgt 1080 gcaatgtcct ttgatttttt ttaatacatt aagagaaaga gaaatatata tatatccacc 1140 cccagcccaa ccgagggcgg cccttggcgg caacatgcaa gaaggaggga ctgtcgaacc 1200 caagggctca aagacgcact cttccaccct tttggagcga atttagaacc tcagccctat 1260 ctccatttcc ctatctggct ctttctctct tgtccctcca tatgatccgc cccgacgccg 1320 tcttctctaa ttaaaatgca ataaggaatc aattcttttc ttgcctgaga aagagaacca 1380 gacgcaggaa gatgaaaggc tgccctttgt tcttcgaatc gtggtggttt tattttattt 1440 ttctttttgt cgctgcactt cctgtttagt tccaagggaa acactttctc tctttctctg 1500 tctctctctt ttcttccttc ttttccttcc tttttgtttc tatctaaata aaagctttcc 1560 ctgtgttgga aagtttttat gtatttaaac tacctaccat gcctgttgtg ctcaggtgtt 1620 tgttcatcct gccatcccca acccttttct acctcaagtc tgtgtgacca ctcacagccc 1680 ccctcccttc gccaaagcag tgtctatgct cttgattaat aaaacatttt ctgaaatcaa 1740 aaaaaaaaaa 1750

<210> 47 <211> 1558 <212> ADN <213> Homo sapiens <400> 47 cagcgagtga gaggggaagg ggcgccaggc gagcacccgg gagccagcgg gacctgggca 60 ggggcgcccg gagcaggcgc gcatggcggg ccccgcgcgg ggatccggcfc ggaagagagc 120 gtagcacggc tcgcacgagt ccggggccga tgtaccaggt gagcggccag cgcccctctg 180 gctgcgacgc gccctatgga gcccccagcg cagccccggg cccagcccag accctatccc 240 tccttcctgg gctggaggta gtaacaggat ccactcaccc tgcggaggca gcaccagagg 300 agggctccct ggaggaggcg gcaaccccca tgccccaagg caatggccct ggcatccccc 360 agggcctgga cagcactgac ctcgacgtcc ccacagaagc tgttacatgc cagcctcagg 420 ggaacccctt gggctgcacc ccacttctgc cgaatgactc tggccacccc tcagagctgg 480 gcggcaccag acgggcgggg aatggtgccc tgggtggccc caaggcccac cggaagttgc 540 agacacaccc atctctcgcc agccagggca gcaagaagag taagagcagc agcaaatcca 600 ccacctccca gatccccctc caggcacagg aagactgctg tgtccactgc atcctgtcct 660 gcctgttctg cgagttcctg acgctgtgca acatcgtcct ggactgcgcc acctgtggct 720 cctgcagctc ggaggactcg tgcctctgct gctgctgctg tggctctggc gagtgtgccg 780 actgcgacct gccctgcgac ctggactgcg gcatcctgga tgcctgctgc gagtccgcgg 840 actgcctgga gatctgcatg gagtgctgtg ggctctgctt ctcctcctga gcctctgtcg 900 ggggctaagc cagcctggcg cccctgcaga ttccagcagg gtccctctga gtggggccag 960 gcccaggact gtcacacaag gcttgagaag ccccctctcc ctggtcctct cctacccacc 1020 catgtcctct cagaacccca gccttgaaaa tagtgggggg cactcagagg ggccacctcc 1080 tcagccgtgg gtggtgggcc catggcagag aagcctgaac tctttactgg gttaccaggt 1140 tcatacattg ctgaggacct gacaggacaa cctaggggca gggctggggt gggggccgca 1200 gagggcagcc agggctgggg aacactgtga aagttacttg gggagggtgg gccggtgggg 1260 ccgtagctct ctacctctcc ctgctcctgg tgcctgcctc tctcctccac cccaggctta 1320 gaggacagaa aaatgtgaag agacgcccca cccaccctca gccagccctc tccagtctcc 1380 tttcctaggc ttttttgggg gcctaaccca cgcagtcacc ccagagggca gggctaggcg 1440 agagcctggg gtggggcggg agggggaaca gtatggaaaa gactggaagg ggaaaggaag 1500 ggaagggagg gaggtctgtt ctatctgttg ctgtaaataa agatatttgt ccatctct 1558

<210> 48 <211> 1720 <212> ADN <213> Mus musculus <400> 48 tgaccaccct ataaaagggg cgtgactcct caacgagcgc cactcgggta cgggagaagc 60 agctggtacc actctggcca ggacctcgga accaagaatc cgcagaagct ggtgacttaa 120 caacccaccg cgctccggtc atggaatctc acaaaaagtg cccctgctgc tactgcactg 180 acttgaagac ctttgttgga gcagtgaagg aggaaacact tcagggtcag tcggtgccgc 240 ctcgacgcgt ttagattcga gaagaactcg ggaggacaac tttttttttt ctgtgcgcgc 300 gcacgtatgc gcgcgcacag aaggtgacga agtgcggtca gcttctcgga ccttcgcagt 360 caccgccgct cctttagagt ggcgcctcgc tcttcccact cttcccagcc ctacctaggc 420 tccaaaccgc ttttcttttt ttttttcttt tttcttttcc cccttctcca gatccacagc 480 ctagcttgag ctcaacgctt ttggagggag cagactacca ggaaaacgcg gaatctgaaa 540 caactttcta ctccgacttt ggagccagcc cgaaggagga agaagtggag atggagaact 600 ctctgttcaa ctccatgttt ctggaagaag caaactacca ggaacccgag ggattcgaac 660 cctcaagagg agaagcagca gcgccggttg cagaagcacc gcaagcctgg aatgggaatg 720 aaaaccttgg aggcggcttc ctggaggcca acgctcagct gggggaggcg gatgoogccc 780 ctgtgcggca gtccctgatg cgtcctctga tgcagcctgt tgctcagtct tcgccgcaac 840 ccctgcccgc aaacccgctg caggccccgc agcagcccga ggagcaggag gaggaggagg 900 aggagcagcc gggggaggag caaccccaac aggagccgaa gcctcgccgc taccgcatct 960 gcttcaccoc gabccaactg caggagctgg aggccttttt ccagcgcgtc cagtacccgg 1020 acctgtttgc tagagtggag cttgcccgac gcctgggctt acctgaacct agagtgcagg 1080 tttggtttca gaacagaagg gccaagtgga gacgacttcg gcgggcacag gcattcagaa 1140 acatggttcc agtcgocatg agtccccctg tgggtgtcta tcttgatgat cattatggcc 1200 ccatccctat tgtggaggtt atttggaagt gctacccaat ggtgcctcgt cccatgcatc 1260 ctcaaatgat gcctcttcca cccaggcccc ctccaggatt cagaatgcct ccaccattta 1320 ggccacctcc tctgccacct tttccctggc cacctgtacc acctgatgcg cacataccca 1380 atgcagcaag ggaatataac cccttcccct tccccttccc ctttcccttt cccttcccca 1440 acccattccc caaccccaac cctaacccca accccaaccc caaccccaac cccaacccca 1500 accaaaattt tgcaggtccc agatacagat actgaagtct acatcagttt tccaaaagtg 1560 tttfctcaatc agatttatat cgtttgtaaa cactatcacg cattacctgt caagaagctg 1620 ttaaacgaaa tgtacaaagt taatgccttc tttgttttga ttttcaataa aagtttggat 1680 tagcagcaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 1720

<210> 49 <211> 68774 <212> ADN <213> Homo sapiens <400> 49 ttaacagatg taaacaataa tatgtaaafct atgttaaaat acctttgcag taaactaaat 60 aagtggatca atgtaatctg cgcagtacat atacaacttc taagaatgca aagctgttca 120 atagcataat gggatttttg ttaaaatttt aattaaattt gtattaaaca ttttgtgagc 180 gatacatgaa aatggaagta ctttgtagtg ctaaaattgt agtgctaaaa tagggggatg 240 ggtggaacag gtttccagtg tcagactcct ttagtttgcc tcccacatta cttacctgct 300 ggatgtccct tgcttaccct ctttgtttct gtttccttaa ttgcaaaatg gaaatagcag 360 tagaacctac ctcatcgttg ttgtgaggat taaatgagta aatacatata aagcattttg 420 gacagtgcct acctcgaata gctcaatgct tcctattacc aggaaacaaa aattagccgg 480 gcgtggtggt gcgcgcctgt aatcccagct actcaggagg ctgaggcagg ataactgctt 540 gaacccggga gggagaggtt gcagtgagcc aagatcgcac cactgcactc cagcctgggc 600 gatggagcaa gactccgtct cagaaaaaaa taaagaaaaa agaaaataaa tctgcacagc 660 catcatctta ttgattccct attaaaaact cctcactggc caggtgtggt ggctcacgcc 720 tgtaatccca aoagtttgtg agaccgaggc gggcagattg cctgatgtca ggagttcgag 780 accagcctgg ccaacgtcgt gaaactccat ctctactaaa aatacaaaaa acattagcca 840 ggcgtgtggc gtgcgcctgt aatcccagct actcaggaga ctgaggcagg ggaattgctt 900 gaaccgggga ggtggaggtt gcagtgagcc gagattgcgc cactgcactc cagcctgggc 960 gacagagaga gactctgtct caaaaacaga caaacaaaac tcctcactct gtccctgtca 1020 ctgaccaaag aagttaccca ttctcaaatt actttcttca tccattgcct ccaattttgg 1080 ctggcaatat ctcccatacc aaaccgttaa cacctggatc cttttagact accggttcca 1140 tagcaggcat tcaaaagtta gtcatttaac tttttcacca gggacaaaag tccttaaaag 1200 aggaaaaaaa ctggaaagga ttacaaatca ccatgtgaag tttaggtgct ctttagcacc 1260 taaagaggat ttacaagata cattgtctgc acggcaacca ctcagacgaa tccaccacca 1320 agcgaaggtt tttagtaaaa tatccttttt tttttttttg agacggagtt tcgctcttgt 1380 tgcccagact ggcgtgcagt ggcgctatct cggctcactg caacctctgc ctcccaggtt 1440 caagcgattc tcctgcctca gcctcccaag aagctgggat tacaggcatg cgccaccacg 1500 cccggctaat tttgtatttt tagtagagac ggggtttcgc catgttggcc aggctggttt 1560 cgaacccctg gccacaggtg atccggccgc ctcggcctcc caaagtgctg ggattacaga 1620 cgcgagccac cgcgcccagc ctaaaatacc cattttaatt gcatttcaat gacgttactc 1680 ggtcattgac ctcttacgca aggagggcga gattagggag acagctggac ttcttcctcg 1740 ccctcccttc actggactgg ctggcgcagt gagtagccct gcccttggac gatttggcat 1800 tttcattggt caatttttct taggaggctg gccgtgtgtt gactccgcct actatatagg 1860 cggggtctcc ccgccgcagg ggctgggatg ctgggggctg ctgaagccgc catcttggat 1920 tccgcggtag cggaggcggc ggtcaggcgc cgcttctggg gagtggcctt tcttttcccc 1980 tccctcccgg ttcggtggcg gcggctcctc ccactggggg ggggggtggc gcggcggcgg 2040 tggcatctgc ggccatggcg gcgactactg ccaaccccgg tgaggagacg gaggactggg 2100 gcgcctctaa aggggagggg ccgaaggggc tgacaactaa ggagacccag ggctgagggg 2160 acgcagctgg agctgaaggc gccggggcgg ggcgggggcc gcgagagacg gtgggggagc 2220 ggtgacctgg ggaggggccc gatcccgggg acttgggtag actcgagtat acccaaggga 2280 gcgagggggc aggtgggagt tgaggggggc tccctgtcct gacctccgtt ggagcggcag 2340 ccagtgcggg gotggcccgc cctcactcct cggtcggcgt ctggtctgtg atgtggtcct 2400 cttttaaccc tctgcccgct ggagccgctt gatgccgaaa actgtaggca gagtgtctcg 2460 gtttacttta agagtagttt ggattcataa accctggacc acactgctct ttagttgagg 2520 cgttgcttcc aaacatttaa aggtttagat tttaatttaa aaaataaaaa atggacattc 2580 tttgatatat acgacgtttc tttaggctgt tacctcccac ccgcaacccc cgtccccgtc 2640 tccgtccccg gactatactt tgaaacttag atcttgtgtt aagagggcct gtaggtcttt 2700 gcctgctgag ggcaggggtt tgtgtaatgg ttatggttcc ggacaggtct ttagttccac 2760 agccccaggt ttaaatcttg ttaggcctac gtcgaggcaa tttccaaact ctttcagaaa 2820 agtttgattc cacaccattt ctcaatttca aaaaataatc aaatatcaaa aaggtttggt 2880 ctgttttgtc taagagatgg agtagggtgt agtgcagttc tagagagatc agatcttcaa 2940 attactagtc ccagccctct ttcctctatg ttacagttat tcctctttag aaggcatttc 3000 attttagggg tctagtttat cttggagacc ttggttattc ttgccaaata aagtctatcc 3060 ttttccaaaa accaatatat ttgatagcct taaaaagggc cttgagatat gtgtgtgtgt 3120 gttgcgtggg gcggagaatt tcttgaaaat aaaacagtag gagtgattac ccccatcccc 3180 acgttgaaat ttaaattaga ttttttttca tgttactgaa aggcagtatg attttgcaat 3240 atccagattt tgataggaca gttgaatcac tgaaatttct tttctaccgt gtttctggga 3300 atagctattt taagaaatgg ttaatttgtc acgtcatttt tttttaatct tttaaatttt 3360 ttttgaagga aagggaggta aaattaatcg caaaaattac attgcaggaa gtgctgagtg 3420 atagaataaa actataaaac aggaaaaatg ccgttatgtc aaacctgacc ttgtagtaat 3480 ataacctatc tgtgaactat ggaataaata aacaagattt ttaactgatc acacattgca 3540 aaatacttat ataaccctag ttaaattgca aagcatttct cttattaaga agtggcctgg 3600 gtaaacaagt tttagttcat atgtcagaag cttttttcca gctgtgtggg tggggttgot 3660 ttattttgtt ttgttttttg aacaacagca accagaatga cagcctcttg accatatttt 3720 cataagctga tcaatatcag cttaaatctt agcagaaaat agcatatgtt agtgtgtatg 3780 tgtgtgtgca gaatccttgt taatgaaaoa gctttgttta ctatgctttg gotgottgot 3840 tctgcaattt ttagatttcc tttttctttt tctttgtttt cctttctcct ctcccctctc 3900 tcctgtcccc tctcccctct ttttcttttg ctacagggtc ttgctccttg ctctgtcgcc 3960 cagtctggag tgcagtggca agatcactgc tcacggcagc ctccacctca ggggctcaag 4020 tgatcctctc acgatcagcc tcccgaatag ctgggactac aggtgccttg ccaccatgcg 4080 cggttaattt ttaaattttt ttgtagagac agatgccttg ctatgttgcc catgctgatc 4140 ttgatctcct ggtctcaagc aagccttgcc tcagtctctc caagttggga atacagatgt 4200 gagacacttt gaccagattt cttttttgat gttgaaaaat tattccatct cttctgactt 4260 attgatccca tgttcagttc aatcaaatca gaagatatat tttctttttt cttttctccc 4320 tttgctcttg tatatcatga ggaagagatc agagatacat tgtggatttt ttcagtagcc 4380 tgttgctttt tgggaaatga gattaatgaa tggagggaca taggtggaaa tgtactgtgc 4440 ttagtgaaag taaatgtttt caggtcagaa ttctttgcta cactgtcata ccttctttcc 4500 ttagagccat tttaaggact agggacacca tgcctatttc tttgagtttt ttctactttg 4560 featttttgct ggagtactaa tttttttttt tttttttttt tttttacaat tcttgttagt 4620 tttgtcaaga ttttaaaaaa tatttcactc tttaaccttc acttcagtta atccttttta 4680 aaaataatac ttatttttat ttttcagaca ggttcttgct ctgtctccca gactgtagtg 4740 caatggtgta atcacagctc actgtagcct tgaactcctg agctcaagtg atcttcccac 4800 ctcagcctcc tgagtatctg ggtctacaga cacacaccac cacacctgga tacatttttt 4860 aactttttgt agaaatggga tcttgctatg ttgcccaggc tgatcttgaa ctcctgtcct 4920 caagcaatcc tcccacctta gcctcctaaa ctgctgggat tataggtgtg agccactgac 4980 ccggccaagt taatccttag ggttagtaat agtgcttgaa catgttaatt gtgctggtgg 5040 ccctgcagtg tttttcaagg ggaccacgtt cttctgcatt tttcactgtg gtgctgcatt 5100 agaagaagag taaaatatgg ttggtactct ctaagagttg tgttgaagta atagttctgt 5160 gatgattttt tttctcgaat tgataattct tcatattcta tcatttttca ctagttctac 5220 ttatcactgg caagtagaac tcggtgggta ggtggtccat gaaactttag gctgtttctt 5280 atctatggac tagacaagtt ttgttttgtt ttttttttgt ttgtttgttt gttttgagac 5340 agagtctcac tctgtcgccc aggctggagt gcagtggtgc tatcttggct cactgcaagc 5400 tccgcctccc aggttcacgc cattctcctg cctcagcctc ccgagtagct gggactacag 5460 gtacccgcca ccacgcccgg ctaatttttt tttttgtatt tttagtagag acagggtttc 5520 accctgttag ccagggtggt ctcgatctcc tgaccttgtg atccgcctgc ctcggcctcc 5580 caaagtgctg ggattacagg cttgagtcac cgtgcccggc ccggactaga caagttttga 5640 ggaacacatt ttttttcccc ataggagagg gtcttgctct gtcactgagg ctggagtgca 5700 gtgacacaat catggctcac tgcagccttg accttctggg agcatgtgat cctcocactt 5760 cagcctcctg agtaggtggg accacaggtg tgcaccaccg tggctggcta attttaaatt 5820 ttttttagag acagggtctt gctatgttgc ccaggctggt ctttaactcc tggcctcaag 5880 tgatcttcct gcgttgggca ctccccaaga gctgggatta taggcatgac caccatgccc 5940 agccaaggtg gaacactttt taaattgaat gtgtcatttg taatgcattg gctgagggaa 6000 cagttgggag gagattaggt atttgattta caattccaaa ttcaaactag agatgttgaa 6060 tgagtttgta gtaagtgtag gtttttatct ctcttgattc tggtattctc attagcagag 6120 aattcttttt gtgetattat gtacaagtta ctgtggatga agaatgtaga aggaaaaggg 6180 taataccgtt tgggtttgta aggctgtcat ttaggaagaa aatttttttt agctaatttt 6240 cacctatata acttagtttt aactgcgtca attaacacaa ttcttacctg ttacctttat 6300 ttaccttttt cagatatggg aaaataggaa ttcatgcaat gtaaagttaa gatgtcaaga 6360 tattctttta tggccaggtg tggtggctcg tgcctctaat ccctttggga ggeegaggea 6420 ggccgattgc ttgagcccag gaatttgaga ccagcccgga caacgtgacg aaaccccttt 6480 actacaaaaa atacaaaaaa ttttccgggc actgtggtgc aettetatag tcccagctac 6540 ttgggaggct gagatgggag tatcacctga gcctggaaag ttgaagctgc agtgagctgt 6600 gatcatgcca ctgtactcca gcctgggtgt tggagtgaga ccctgtcccc caacaaaaaa 6660 agagatagta ttttattata ttgcaaaggc cttttttttt tttttttttt ttttttgaga 6720 cagggtctta ctgtgtcgcc caggctggag tgcaatggcg tgatcttggc tcactgcaac 6780 ctcogcctcc tgggttcaag ctattctccc gcctcagcct cccgagtagc tgggattaca 6840 ggcacctgcc atcacgccgg ctaatttttt atttttaata gagacagggt ttctccatgt 6900 tggccaggct ggtcttgaac tcctcacctc aggtgatccg cccaccttgg cctcccaaag 6960 tgctgggatt acaggcgtga gccgccatgc tccgccgcca tctgttttta agaatgctgc 7020 cttggccggg catggtggct catgcctgta atcctagcat tttgggaggc cgaagtgggc 7080 agatcacctg aggteaggag ttcaagacca gcctggccaa catggagaaa ccctgtctct 7140 actaaaaata caaaaattag ccaggcatgg tggcaggtgc ctgtaatccc agctactcgg 7200 gaggetgagg egggagaate gcttgaacct ggaaggtggt ggttgcagtg agetgagate 7260 gtaccactgc actctagcct gggcgacaga gtgagactcc gtctaaaaaa aaaaaaaaaa 7320 aaaaaaaaac cacgactgcc taatatgcca taatgacttt agtaagtaga catcagtgaa 7380 tcttcaggtt ggaaatatga caacacctat cattttacac ttaaggagac aaacccaggg 7440 aaaggagtgg ataattaagt tccttctata tgccaggctg cactttccta ttttgttgct 7500 aatctttatg tctagtctgt agcaactgtc tccaactttt cacataaact cttcaaattt 7560 atgtcacttt tcataatttc gtcaatgtat tttcttgttt taaagttttt attattttag 7620 atagtgaccg ggtctcacta tattgcoocg gotggtctca aactcctggg ctcaagcaat 7680 cctcctgcct cggcctccca gagtgccggg gttacaggtg tgagccaocc totgaggccc 7740 attttatatt ttccctccac gttttcattg tagttgaatg gacaagtaag tttatggatt 7800 caacagtata cttagggctg gacatggtgg ctcatacctg taatcctagc actttgggag 7860 gctgatgtag gtggattgct tgagcccaaa agtttgagac cagcctgggc aacgtggtga 7920 aaccccatct gtacaaaaaa atacaaaaaa ttagcagggt gtggtagcat tccctgtagt 7980 cccagctacg tgggagactg agatgcgagg atgacctgag cctgggaggt tgaggctgca 8040 gtgagccatg attgtgccac tgcattcctg tctgggtgac taggagacag agtgagaccc 8100 tgtctcaaaa aacacaacaa aaccagcata cttaggatat aagttccatg agagcagaac 8160 ttttgctttc cttgtttacc agagcattgc agtgcttaca gtgggtgcct agtatgttgg 8220 attagagttc aatgtatgtt tgtggaataa aaatgaatgt aaaacccact gttaatatga 8280 aatacctttg aagggataaa actaattaag ccattgacat catgaatttg tactaactat 8340 aataatatct aatatttatt agtaatactt accagctgtt ctcatttaat ttttataaca 8400 atcgtattag gtaagtatta ttattcttgt tttacagatg aggaaactaa ggcacagaga 8460 gtgaataagt aacttgtctg aagtcacata gctactagaa gttagagaca gaattttatt 8520 gttggcagtc catctacaca gtcatcattc ttaatctcca agttatgatt ttttccattg 8580 tgacttagag tcaccttcct actgaaatat agtacaatgg atatcttttg agaaggaggt 8640 aggtggagta ttgtcttttt tgtagatgaa aagggtgaaa taccacatta ggcagcctgg 8700 gggcaaggca ttgcttggtt ggagaaccaa gtgcaaggtg ctaaaaaaag gagctagaac 8760 agtagtttcc aggctgagtg tggtggctca tacctgtaat ctcagcactt tgagaggcca 8820 gggtgagagg attgtttaag cccaggagtt ggagaccagc ctgagcaata tagggagacc 8880 ttgtctccac aaaaatatat ataaaaaaat tagctagatg tggtggtgga tgcctatagt 8940 cccaactact tgggaggctg aggtggtggg aggatctctg agcttgctag gtcagggctg 9000 cagtgagcca tgatcatgcc actggactct aatctggttg acagagtgag cccctgtctc 9060 taggaaaaaa aaaaaaaaag gagrtagtttc ctaaaatctt ttctgtaaca ttctataatt 9120 cttcattttg ttttgttttg tttttttgag actgagtgtc cttctgtcac ccaggctggg 9180 gtgcagtggc acgatctcag ctcactgcaa gctccgcctc ccaggttcac gccattctcc 9240 tgcctcatcc tcgcgagtag ctgggactac aggcatccac caccatgccc tgctaatttt 9300 ttgtgttttt agtggagatg gggtttcact gtgttagcca ggatggcctc gatctcctga 9360 ccttgtgatc cgcccacctc agcctcccaa agtgctggga ttataggctt gagctagcgc 9420 gcccagccta acattctata tttctttctc ctagttctat gtttcaattc tttaaatact 9480 tttaagggtt tttttgagac aaggtcctgt tgtgtcagcc aggctggagt gcagtagcgt 9540 gaccatagct tcctgcaaca cctceaattc ctaggctcaa gcgattctca ctcctcagtt 9600 tcctgaatag ttgggaccat aggtatgcac catcatgccc agctaatttt ttaattttgt 9660 agagacagga tctcgctatg ttgcccaggc tggtcctttt ttttttaaat tttattatta 9720 ttttttgaga cggagtcttg ctttgtcacc caggctggag tgcagtggcg tgatctcggc 9780 tcactgcaac ctctgcctec cgggtttaag cgattctcct gcctcagect cetgtagctg 9840 ggactacagg cacgtgccao ogcgcctggc taatttttgt gtttttagta gagacggggt 9900 ttcaccatgt tggccaggat ggtctcgatc tcctgacctc gtgatctgcc cacctcggcc 9960 tcccaaagtg ctgggattac aggcgtgagc caccgcgccc ggcctgccca ggctggtctt 10020 gaactactgt cctcgagtga tcctcctgct gttggcctcc cagattgctg agattacagg 10080 catgaatcat gcactgcagc ttttaggatt gttattagaa tcctctacaa gttcttgata 10140 ctccataatt gagcctctcc tagaaactbg gtttcagaga cactgttgct agçrtctttat 10200 cactgattgt tccttctttg tcctttttgc ttatctttct gcttgtttct ttctcttgtt 10260 cagtatgctt ctacttttct cttctcaccc ttgaggctag gactcttctt tgagacaggg 10320 tcttgactct tttttgagac agggtcttgc tatgttgccc acgttggtct tggattcctg 10380 agctcaaatg atcctcccac ctctgcttcc tgagtagctg ggattacaag tgtacaccac 10440 agtgcccggc ttggggctag aactaaatag taaaccaagc agtttccttc atttcttccc 10500 atttgcccac ctacctgcct ttctagctgc ttgccttcct acttcaattt gacattcact 10560 tggtacctac catagtcctc ttccctttgt attagtccat tctcacactg ctataaataa 10620 ctacctgaga ctgggtaatt tatgaagaaa agaggtttaa ttgactcata gttccgcagg 10680 ctgtatggga ggcagggctg gggaggcctc aggaaacttg gaatcatggc ggaaggcgaa 10740 ggggaagcaa gcatgtcttc acatggctgg caggatagag ggagagaagg ggaaggtgct 10800 acacactttc aaacaaccag atctcttgag aactctatca tgagagagca ttaggggaat 10860 ggtgctaaac ctttggaaac cacccctatg atccaataac ctcccaccag actgcacctt 10920 caacactggg gattacaatt tgacatgata tttgggtgga gacacacaga gccaaaccat 10980 atcacccttt atttatcttt tatgtataaa agactccaaa aatttcattc ctggcttctc 11040 acataaacta ctttcctata tttttatcta tttaaaagat atctctctct ttttctttta 11100 aagttgagac agggttttac tatgttgccc aggctggtct tgaaatcctg ggctcaagca 11160 ttcctcccac ttcagcaacc tgagtagctg gactacaggt gtgtgccatt gtgcctggct 11220 gcatctctgt ttgaatagtt tttttttttt ttaatttata gaaatgaggt ctcactgtat 11280 tgcccagact ggtcttgaac tgotgagctc aagtagtccc cccatcttgg tctcoctagt 11340 agctgggatt ataggtgtat gacacgatgc ccagctctat ttgagtaatc tgtttttttt 11400 tgttgttgtt gtttttttta aagacagagt ctttctgtgt tgcccaggct ggagtgcagt 11460 ggtgcgatct tggctcaccg cagcctccgc ctcctaggtt caaatgattt ttgtgcctca 11520 gcctctcgag tagctgggac tacagtgtgc caccacgcct ggctaatttt ttgtatcttt 11580 agtagagatg gggtttcacc atgttggcca ggctggtctt gaactcccgt cctcaagtga 11640 tccacctgcc ttggcctccc acagtgctgg gattacaagt. gtgagccatt gcgcccagcc 11700 tctatttgaa taatctttaa catcctatat atgtatgtac tcaccagtat ttcctttaaa 11760 tctgctgttc ttcctacctt tctgtatctt tcatcactat cacaattcag tttttcattt 11820 ccccaggota aggaactata agtgtttgga ttttattttt tatgtgttta tctgggttat 11880 taactcttot caggtctttt gocaaatata cgtgtgtgtg tgtgtatatg tatgtgtgta 11940 tacatacata tataaaagtt atttaaatca aaactataca tccàtatatt aatatttaaa 12000 gacttagata gttttataaa atgtttgtta caaaaaaatt ataagggagt cctctgctcc 12060 ctttctotca tttccttctc tccagtggca toatttttat ttcttttaao agaattcttt 12120 çtttctçttt aaataaagtg tcccaQ'tnaa açacattaQ^ ttccaçatca sagçgçctgt 12180 gcacacatca aggcccatta tgctgaaatt tcagcatcag atagagaata tcctataagc 12240 ttcagagaga ataagattat tcacattcaa aagattcagg tatcagattg gtcttttttc 12300 tcagtagtca tgctggaaag tagaagacct tggaacaggc tgactgacct tggtggctca 12360 cgcctgtaat cccagcattt tgggaggctg aggcaggtgg atcacctgag gtcaggagtt 12420 tgggaccagc ctggccaaca tggtgaaacc ccgtctctac taaaaataca aagattagtt 12480 ggacgtggbg gtgtgtgcct gtagtaccag ctacttggga ggctgaggca ggagaattgc 12540 ttgaacctgg gaagcagagg ttgcagtgag ccgagatcac gccactgcac accagcctgg 12600 gcaaaagagc gaagactctg tctcaaaaaa aaaaaaaaaa actttggagt aatgccttca 12660 aaattctgag ggaaaataaa ttctaattta gaattccata gctaggcaaa ctatcaatta 12720 gtgaaataga agaaatattt tcatacatcc aaggcatttc ttacaccctt tcaggaatcc 12780 actagaagat aggctctacc agtaggagat agtaaaccaa gaaagtggag atacgaaata 12840 taggaaatag gcagtataac acagaagaaa aatgaagcat gtagtatgca tacattggtg 12900 ttagttttcc tgttttcagt acgggtccct cactttcacc tttacgtcgt gttcactaga 12960 ctgtaagacc tttgatttat actctccaga gagtaaatct gtcttttgac agaatggaga 13020 ggggtagttg ccttggttag aaggaataga gaaaaggatc taggaatcca tctctgtagt 13080 aaacagatgc tgaaotaatt ctccttattt tcacttcatt caccctaccc tgcataccca 13140 gagttacctg gactcaccag cttctgagac tttggggaat tccatagcgt aaattgagtt 13200 ggttttctgc tttttccctt gtcagtttag gatttagttc ttgtcgatct cccaaggcaa 13260 tagtccattt tatctctagt ttcaaaaaaa ttattgctct tcttctctta ttctttccat 13320 ccttgtggtt ttatgtcttg tgtaaaaatt tttgctttta aaaatttttt tcctgtgtgt 13380 gagtgaagag agaagagagt agaaatagat agatacattt aattcactat ccttactcag 13440 aagttgcata gtttaaaatt ttagaagtaa ctaccttttc gttgtgccat cctcatttag 13500 gcctttatca ccttgttttt tttattaatc ttgtcttcct acttctatta cttcaaactt 13560 taaatctgtc agattaattt taatttatat tttcatcttg ttactcagac ttaaagttat 13620 atgtttgtct ttgttgaatc tgatccaggt gtttcatcgt ggcattcaaa gctttctctt 13680 ggttagcact tgacatctta ccttttatag gtctttttct ttcttttttt tttttttttt 13740 gattfcaaaga aaaccatttt gttttcttca ggggcaattt tttttttaca ttccaccaca 13800 tattatttat atgtttatca tatttctttt atttatttat ttatttattt atttattttt 13860 tattatactt taagttttag ggtacatgtg cacattgtgc aggttagtta cat.atgt.ata 13920 catgtgccat gctggtgcgc tgcacccact aactggtcat ctagcattag gtatatctcc 13980 caatgctatc cctcccccct ccccccaccc caccacagte cccagagtgt gatattcccc 14040 ttcctgtgtc catgtgatct cattgttcag ttcccaceta tgagtgagaa tatgcggtgt 14100 ttggtttttt gatcttgcga tagtttactg agaatgatga tttccaattt cgtccatgtc 14160 cctacaaagg acatgaactc atcatttttt atggctgcat agtattccat ggtgtatatg 14220 tgccacattt tcttaatcca gtetatcatt gttggacatt tgggttggtt ccaataggtc 14280 tttttcttta cagctcttca cagttgctgt tatgtgtcae ctaatgacac tttggtcatc 14340 aaaggactgc atgtatgatg gtggtcccat aagattataa tggagatgaa aaattcctat 14400 tgcccagtga catcatagtt gtcataaggt cttagcacaa cacattactt tttctatgtt 14460 tagatacata aatagttacc actgagttat agttgcctac agtattcagt atagtaacat 14520 gttgtácagg ttgggagtaa taggctgtta ctgggagtaa taggctacat ataggtatgt 14580 aggctataca cctacatacc taggtgtgta gtggctgtac catctagatt tgtgtaagta 14640 tactcaatga tattcacaca atgttgaaat ctcctaatga cacatttctc agaacatatc 14700 cctgttgtta agtgatacat aactgtattt tcatatctcc ctttagactt gctcatgtac 14760 ttttatctat gtggaatgcc tttttcttct tctttacttt ttttttttga gacggagttt 14820 tgctcttgtt gcccaggctg gagttcagtg gctcgattgg ctcactgcaa cctctgcctc 14880 ctgggttcaa gcaattctcc tatctcagcc tcctgagtag ctgggattac aggcgcctgg 14940 taatttttta tatttttagt agagacgggg tttcaccatg ttggtcaggc tggtctcgaa 15000 ctcctgacct taggtgatcc acccacctcg gcctcccaaa gtgttgggat tacaggcgtg 15060 agccactgtg cctggtctcc tttacttttt ttaaggccca gtttgattta cctttttgaa 15120 acttccccat gggctggttg cctgccttct ttatttcctt tagtttcctc ttcatattga 15180 gcatcttctc tgcaagtact atgccaggcc ttaatttaaa ccaggattat cttctctgaa 15240 tttacctggc actctttttt ttttttttga gacagagtct cattctgttg cccaggctgg 15300 agtgcagtgg catgatctcg gctcactgca gcctttgcct cccaggcgat tctcatgcct 15360 cagtctccca agtagctggg attatagacg tgtaccacca cacctgacta atttttgtat 15420 ttttagtaga gacgggattt tgccgtgttg gtcaggctgg tctcaaactt gaccttaagt 15480 gatctaccca cctcagcctc ctaaagtgct ggggttacag gcatcagcca ccgtgcctgg 15540 cctccatggt aatctttttt tttttttttt tttgagacgg aatcttgctc tgtcacccag 15600 gctagagtgc agtggcacga tcttggctca ttgcaacctc cgccttttgt gttcaagcga 15660 ttcttctgcc tcagcctccc gagtagctgg gactacaggt gtgcgccacc atgcctggct 15720 aatttttgta tttttagtag acacggagtt tcaccatatt ggccaggctg gtctcgaact 15780 octgatgtcg tgatctgcct gcctcggcct ctcaaagtgc taggattaca ggtttgactc 15840 catggtactc ttatatccta tataaacgta ttactaaaag tatgaacttt tttttttttt 15900 tttttttttt tacagaggca ggatctcact atgttgctca ggctagtttt gaactcctga 15960 gctcaagcaa tcctcatgcc ttgacctccc aaagtgctgg gattataggc atgagccact 16020 gcacttggcc ctgaactttt ttttttaatg gaaaaagtgt tttttcttag gaaagtaaca 16080 tatgcttact atttcaaatt tataggctga aatagaaaaa ttagcagtaa cataaaaata 16140 tactcagcct taatgtatgt taaactaaca gtggtaattg ttttttacca agaaaatgac 16200 cacaaatttg aaggattccc aaaacacagt gctgttggag gtatggctaa attgatgcag 16260 tggatgaggc tttaaattgg tataacctcc ttggcaggta atgggcaatc agagttttaa 16320 atgtgtctac ccttaggccc agggagtcat tttcagaaat aatatggaag tactggcacc 16380 tgtgcatgaa gatacacaat gatgttcctt gaaacattat ttataatagt gaaggtttga 16440 atgtcataac tatacattta tagtacagag tactatgtaa ctgttaaaaa gaatgatcta 16500 cgtgtgtatt tattgccata gcaatatatt gttacgtgga agggaaaaag ttcagaataa 16560 gtacatctgt acttatggtg gggttatggc ttgataaacc cattgtaaat tgaaaacatc 16620 ctaagtcaaa aatacattta atacacttaa cctattctta gcctagacta ccttaaatgt 16680 gtgtggaata cttacattag cctgcagtgg gcaaaataat ctaacttaaa ttctacttta 16740 taataaagta ctggatatta tgtaatttac agaacactgt acattacact gaaattgtaa 16800 tgçrtttccca ctatcataaa ggtgaaaagc cctacatgga accattataa gtcaggactg 16860 tttgtatagt atgacccttt tttttgggta aaaattaccg aaaccctggc tgggcgtggt 16920 gactcatgcc tgtaatcagg cacataccac atgtatggcc aattttgttc atttttttta 16980 gagatagggt ctcactgtgt tgcccagggt ggtcttgaac ttctggactc aaatgatcct 17040 cctccctcgg ccttttaaag tgctagcctt acaggtgtaa gccaccatgt tcagccccac 17100 agtttcttta tccgttaacc tgtagataga cacttgggtt gccctcaccc ttgactactg 17160 ttgaatagta cttctgtgaa cgtgggtata caaatgtttc tttgagaccc tgctttcaat 17220 tctttcaggt atatacccag aggtggaatt gctggatcat gtggtaattc tatttttaat 17280 ttaatttttt ttttgcgatg ttgtcttgct gtgtttccca gcotgatctt ggactcaaga 17340 ttctcctgcc tcagaccccg agtagctggg actacaggtg cgcaccactg cacccagttt 17400 tatttttaat ttttggaggc atctccatac tgttttctat tgctgttacg ccattttaca 17460 tttccactag cagtgcataa gggttttaat ttctccacat ccttgccaac cctttattta 17520 tttatatatt tttggataat agtcatctta atgagtagca aatgctttct cattgtggtt 17580 ttgatttgca tttccctagc gattggttat gttgagcact ttacatgtat ttattggcca 17640 ttagtatatc ttctttgtag aaatgcttgt tcaagttctt tgcccatttt aaaattgggt 17700 ttgctttttg ttgagttgta ggagctcttt atatattttg ttttattttt tatttgttta 17760 tttttttgag gcagagtctt tctctgtcgc teaggctgga gtgcagtggt gcgatcttgg 17820 ttcactgcag tctccgcctc ctgggttcaa ttaattctoc ctgcctcagc ttcccgagta 17880 gctgggatta caggtgccca ccaccattcc tggctaattg ttgtattttt agtagagatg 17940 ggatttcacc atgttgatca ggctggtctc gaactgctga cctcaggtga tatgcccgcc 18000 ttggcctccc aaagtgctgg gattacaggt gtgagccacc gtgcctggcc actctttata 18060 tattttggat attctgtgtt gcatatatga ttcgaaaatt tttttttctg ctgggcacgg 18120 tggctcatgc ctgtaatcct agcattttgg gaggctgagg tgggcggatc acttgaggtc 18180 aggagttaaa gaccagcctg gccaacatgg tgaaacccca tctctaataa aaatacaaaa 18240 attagccagg cgtggtggtg cgtgcctgta atcccagcta tttgggaggc tgaggctcga 18300 gaatcacttg aacccgagag ttggaggttg cagggagcca agattgcgcc actgcactcc 18360 agcctgggcg acagagtgag actctaactc aaaaaaaaaa aaaaagaatt tttttttttc 18420 tattccatgg gttgcctttt cactctgttg gtagtgttat ttgatgcaca aaatattgta 18480 cactatacag tatgaactaa caaaaaacaa tgagatgtgt gtagatagat attcatgatg 18540 tatattgaaa tgacgagcaa gttgaagatc aggcctccat tttttactaa gagaaaaatg 18600 cacccttttt ttttttttag acaggatctt gctctgttgc ccagggtgga gtgcagtggt 18660 gcaatcacga ctcactgcag cctcgacttc ccaggctcaa gtgatcctcc cacatcaacc 18720 tcttgagtag ctgggactac aggcatgggc caccatgctg gctaacttgt attttttgta 18780 cagatgaggt ttcactgtgt tgcaaaggct agtctcgaac tcctgggctc aagtgatctg 18840 cccaccttgg tctcccaaag ctctaggatt ccaggcatcc gccactgtgc ccagcctgca 18900 cctctttttg attacagagt. taggtatata taaactgaga ttgaaaaata agagaaaata 18960 tactcagggc tgggctcagt ggctcaaacc tgtaattcca gtgctttggg aagctgaggt 19020 gggagtattg cttgagctca ggagtttgag accagcctgg ggaacacagt gagaccctat 19080 ctctacaaag aaaaaaaaag aaaaaaaaaa tcaccgaggt gtggtggtac ccatctgtag 19140 tcccagctac ttaggaagct gagacaggag gatcactgga gcccgggagg ttgaggctgc 19200 agtaagccat gatcatgcca ctgtactcca gcctgggctg gacaaagtga gaccctgtct 19260 taaaaaaaaa aaaaaaaaag tactcagctg ttactaatgg ttactgctgg gggatgagat 19320 tgaattggaa ggagagagga gaggtacggg gggcaggaaa gggagacaat aatgagggac 19380 tttcagtttt actttacata attttctttt aagtattgga atttaggtga tttttccttt 19440 ggggttttct gtattttcca atcacaataa ataaaataag ttataaatat ttgttgcatg 19500 aatgaaatgt ataaacccat ttatgtatgt atttttttaa aattagtata ttattaagtc 19560 tatacaatat tagtatattg ttatgtatgt ataagctttt taacatgaag tttgcagaat 19620 atagtacttc ttccaaactc tatgacatgg ggggaactga agtatgggga tatcttgtac 19680 cagtgtaaga attcaagaag agaccgtgtg tggtggctca tgcctataat cccagcactt 19740 tgggatgcca aagcaggatg atctcttgga gctaggcgtt caagaccagc ctgggcaaca 19800 tatcaagacc ccatctctaa aaaaaaaaaa aaaaattaac tgggtgtggt agtgcgggcc 19860 tatagtccta gctattccag aagctgaggt gggaggattg cttgagccca ggagtttgag 19920 gctgtagtga cctataccag tgattatacc agtgcactet agcccaggca acagagtgag 19980 acctggtctc aaaaaaaaaa aaaaaaatca agaagagcaa tctggatatg agcatttggg 20040 atttttagca aactgctgag attttgtcta tagcttgaac ctttctttta gctaacttga 20100 tgatactgat gataagcaag gactgtcttt ttaaaaatgt ttacttcatt attttcctga 20160 cagaaatgac atcagatgta ccatcactgg gtccagccat tgcctctgga aactctggac 20220 ctggaattca aggtggagga gccattgtcc agagggctat taagcggcga ccagggtgag 20280 tttgagtgta gtgtgttatg aatatctctc ctataaacca actttagttg ctgaatttat 20340 ttagttgctg aactcacttc gctattcctg accatctcac ttcaacttga ttacttacta 20400 cactactgtc atataagtct ccttagtccc tgtatttttg tttatgaaga atttgttttt 20460 atccaagttt cccgtaagca gttctttttt taaaccaaaa tttccgtaag ataaaggact 20520 gtagctaagc ccagagattt tactatgcct gagaaaactg tttgctgctt tcattaagct 20580 ttgtttctgt tttcocaaaa tcattttggt aggctgcttt tctgaattta gagaatgctg 20640 agctctagaa tagctgtctt otaagttatt gatatgttgc ttggtttgga atgcagagte 20700 cattcagctc caaaagtatt tattaaattc ctaattagtg ttatggcatt gtgctgattc 20760 caagtaggat acaaagatga ataagacaca gtccttgttt ctaagttggt tgtgttctga 20820 tagaaataat tattatacac atgaatatat gatagaatat gcctagtttt gttaggaaca 20880 aatttgatac tatgttttto tgtgtatgga aatatgcatt tgttggtaaa gactgagaaa 20940 agcttcagaa aggaggttgc cttagagggg cctggaagaa tgggcactat tttatttact 21000 ttttggtatt aaattttcct ttttccttct ttttcttttt aaaaattgtg cagctaatta 21060 taaccagtct ttaagttttg tcccaccaat agtaatggaa gaçrtgatgct tgggttcagt 21120 ggtaacatga gtaacatatt aagacttgtt atatgttcag tagctttaca gattttaacc 21180 atttgctgaa gcataagctg aataagtaac tttctaagat tgtaaagcta gtaagtgtca 21240 gatataggat atgaacctta ggggtttagc tttgtagctt actctttaaa cactgtgtta 21300 tgtttatgta cagtaacaaa caaaagtatt ataaatatca aaattagggc atcacttgag 21360 aaagtcatag tatatttaaa atggaatgct atgtagttat aagcgacaaa tatgtttcag 21420 tgtagaaaga tgttcacaat ctattaagaa aggttacagt attatagtat ttcactgtca 21480 aaagatatgt ataacatgta cataggaaaa aactgaaaga atatatacca catttctggg 21540 taatagtatt atgggtgact tacggtttct tttgtttttg atttttcaga tttttgaaat 21600 gaacatgtat gattggtaat cagaaaaata tattaaagga agtctttaaa aattttcttt 21660 ttggtttttt tagagacagg gtcttgtacc ctggctggag tgcagaggca caatcatggc 21720 ccactgcagc ctcaaactcc tgctcaagca gtcctcctgc cttggcctcc caaagtactg 21780 ggattacagg cgtgagccac ttcacctgte ctaaaagaag tcttttaata tttcttttat 21840 ttttatttac ttatttattt tcgaggcaga gtcttgctct tttgccaggc tggagtgcag 21900 tggtgtgatc ttggctcact gcaatctcca cctctctggt tcaagggatt ctcctgcctc 21960 agcctcccaa gcagctggga ctacaggcgt gcgccaccac gcccagctaa tttttgtatt 22020 tttagtagag atgggatttc accacgttgg ccaggctggt ctcgaactcc tgacctcagg 22080 tgatatgccc accttggcct cccaaagtgc tgggattaca ggcatgagcc accatgcccg 22140 gcctaatatt tcttttattt atttatttta ttttttattt ttttgagatg gagtctcgct 22200 ctgtcgccca ggctggagtg cagtagtgtg atctcagctc actgtaacct ccacctccca 22260 ggttcacgcc attetcctgt ctcagcctcc cgagtagctg ggactacagg cgcccgccat 22320 gatgcccgac taattttttt gtattttcag tagagacggg gtttcaccgt gttagccagg 22380 atggtctcga tctcctgacc tcgtgatcca cccgccttgg cctccogaag tgogggatta 22440 caggcacgag ccactgcacc cggcccatat ttcttttaaa gaaagattgg aaaatacaga 22500 aagttagaaa gaacaataaa aaggccaaaa tctactacca tgttttttag tgcatgtcct 22560 tcagtcttta tatgtaaatt gtttttaata gttatgtaat tatatagttt tacatggcct 22620 agtcttttca ccttatataa ataataagca atacacacgc acacacacat tttggcacct 22680 tatataaata ataagcaata cacacacaca cacatttcgg agacagagtc ttgctctgtt 22740 gcccaggctg gagtgcagtg gcatgatcat ggctcattgt agcctcaact tcttgggccc 22800 aggaagcaat cetcctactt cagttctccg agtagctggg accacaggca catggcacca 22860 tacctggcta tttttttttt tttttttaaa gacatggtct cactacgttg accaggctgg 22920 tctaaaactc ctaggctcaa gcagccctcc catctcgacg tcctaaagtg ttgggattac 22980 agacatgacc tactgtacct ggccctttaa aaaaatattg ttacatattc tatataaaca 23040 taatttttat ttattttttt ttgagacgga gtctcgcttt gttgtccagg ctggagtgcg 23100 gtgatgcgat cttggctcac tgcaagctcc gcctcctggg ttcatgctat tctcctgcct 23160 cagcctcccg agtagctggg actacaggcg tccaccacca cgtctggcta attttttttt 23220 tttttgtatt tttagtagag acggggtttt accatattag ccaggatggt ctccatctcc 23280 tgacttcgtg atccgcctgc cttggcttct caaagtgctg ggattacagg catgagccac 23340 tgcgcacagc cataaacata atttttaatg gttgcgtgaa aggatgtact taacttccta 23400 ttttgggaca tctaaattgt tttgaagatt ttgctgttac atatgatgct aaaaagaact 23460 tctttgtacc taaacttttt tttcctattt catattattt ctttagattc ttagaaatag 23520 agttattggg ctgagcacgg aggctcatac ctgtagtgcc agcactttgg gaggctgagg 23580 taggaggatt acttgagccc aggaattcaa gaccagcctg gggaaaatgg cgagactttt 23640 ttttctttga cttagcaatt atctttcttt tccttccttc cttcattttt ttcctttgac 23700 ttagcaatta cctttccctc cctccttcee tctctttccc cttecctttt tttttttttt 23760 ttttttgaga tgtagtttcg ctcttgttgc ctaggctgga gtgcagtggc gcaattttgg 23820 ctcactgcaa cctctgcctc ccgggttcag gcaattctca tgcctcagcc tcccgagtag 23880 ctgggattac aggtgcccgc caccacaccc agctaatttt tgtattttta gtagagacga 23940 ggtttcacca tgttgactgg gctggtcttg aactcctgac ctcaagtgat ccgcctgcct 24000 cagcttccca aagtgctggg attgcagatg tgagccacag tggctggccc cttttctttt 24060 ttgagacagg gtcttgccat gtcactgagg ttggagtgca gtggcccaat ctcagctcac 24120 tgcagccttg acctcccagg ctcaaggcct gcagcccctc ccgccccccc aacccaagta 24180 gctaggacta cacatgcgcc accatgcctg gttagttttt gtatgttttg tagagacggg 24240 atttcaccgt gttgcccagg ctggtcttaa actcctgagt tcaagtagtc tgctcgcctt 24300 ggcctcccaa agtgcgtgga ctacaggtgt gagcaaccat gcctggctga gattttttaa 24360 aataaaaaaa tttagttgag tgcagtggtg ggctcctata gttccagcta attgggaggc 24420 caagatggga ggatcccttg agcccaggag ctcaaggtgg cagtgagcta tgatcatgoc 24480 actgtactcc agcctgagta acagagtgag agcttgtctc ttaaaaagaa agaaaggaag 24540 agatagagag aaagaaagaa tttgagttac tgggtagata gataggattt tacaggtgac 24600 cagattaggg gattcaggaa ggaggaagag gagcaaacac tttcaggatt gatgctgtat 24660 gtgtacttca aatgcgaccc atctagaggc ccataatatc aaggtatccc aatagtagaa 24720 gtaaaaagag tgatcactag gttaaggtgg taacatgagc aatattttag ttcaatagtg 24780 tacagagatt ataaggggat tggtctattt tattgtttat aatctttcct aatctccttt 24840 aaagaaattc acttcttctt tccctgaatg tctgtagcat gttgattgta ccccttatgt 24900 gacactttcc tattctcact tgttttatat ttgtatttct otaggtgaag agccccttga 24960 gggcaaggtt cttgttttta cctcacctag cacagtgtct tgaatgaagt atatattaca 25020 tgtttattag atcaatgaag gaaagaaaca ttatctaaca atcttcgtag gtattaagtc 25080 actcctbtat gtaagatcac tgctttgaaa gatgtttcag aaatttggta acacggctta 25140 gagcagactc tagaaatgaa acatggacct gaattattta cgttaatttt ttcttatttt 25200 ttctgagtgg attcctgctc cctttacaga ggttgtagtc tgattgaaaa ctctggcaaa 25260 gatfcgaotgc tactctagga aagtgttaag gtagoagaag gtacttttgt ttctattgcc 25320 cagttttgta cttttttttt ttgagatgga gtcttgcagt tgtcgcccag gctt.gagt.gc 25380 aatggtgcga tcttggctca ctgaaacctc cacctcccgg gttccagcaa ttctcctgcc 25440 tcagcctcct gagtagctga gattacaggc acccgccacc atgcccagct aatttttgta 25500 tttttagtag agatggggtt tcagcatgtt ggccaggctg atctcgaact cctgacctca 25560 ggtgatccac ccacctcagc cttccaaagt gctgggatta caggcgtgag ccaccactcc 25620 tggccccagt tttgtacttc tttgcctagt ttgggactat gaacaagagg aaatgtagct 25680 ttgtttgact tctgccactt cctctttcca ttcttccatt tgggtgggtg ttccggtagc 25740 ttgtgttgag aaattttaac ttcttaatgt tttgtattat cagcaggctt aaagtattta 25800 ttgttggctt tcctcaggct ggattttgat gatgatggag aagggaacag taaatttttg 25860 aggtaagaga ctgaaaaact ttccttagat gtctgatatt aaaaattagt ttatgatctt 25920 tatacttctg acttgtaaat ttttgtcctt aggtctaagg agagtacttc atcctaaaac 25980 tataaatatt catatatctc agaaaatttt taagcattcc gttaatatct ctagagaaag 26040 gacctcagtg aggagaggac ggcatttaca aaccctctgt atcagttctc tgctacttca 26100 tagcctaaaa agaacaacag ttcgttattt ctcaattctg tggattgact gcatgtttat 26160 tctgcttatc tcacctagac tcactcataa gactgcattc tcagctggtc agctgagaac 26220 tggactcagc tgggatggct gggtatttct gtctatgtgt ttttttatcc tcaaggaggc 26280 cagactgaat tttttcatgt ggtgatggct acaatctaca gcacaaatcc cagtgtgcaa 26340 gtgcttatca agcctctgct tatatgacat ttgcttatgt cccattggcc aaagcaagtc 26400 atatgttcca ggtgrtgagtg tgtgaggggg ttacacaagg aagtacatac tgagaggtgt 26460 aattcattgg ttgaggtgtc attaatctgt gactctgtca taccctctga cacctgttga 26520 cacctcttat aggbagcagg aattggaatt tgtatttttt gtttttgttt tttttttttt 26580 tgagacggag tcttgctctg tcgccaggag tgcagtggtg caatctcggc tcactgcaac 26640 ctccgcctcc tgggttctag cgattctcct gcctcagcct cccaagtagc cgggactaca 26700 ggtgcgtgcc accatgccca gctaattttt gtatttttat ttttttattt tttattaatt 26760 ttctttttta ttgatcattc ttgggtgttt ctcgcagagg gggatttggc agggtcatag 26820 gacaatagtg gagggaaggt cagcagataa acaagtgaac aaaggtctct ggttttccta 26880 ggcagaggac cctgcggcct tccacagtgt ttgtgtccct gggtacttga gattagggag 26940 tggtgatgac tcttaatgcg catgctgcct tcaagcatct gtttaacaaa gcacatcttg 27000 caccgccctt aatccattta accctgagtg gacacagcac atgtttcaga gagcactggg 27060 ttgggggtaa ggtcatagat caacagcatc ccaaggcaga agaattttto ttagtacaga 27120 acaaaataga gtctcctatg tctacttctt tctacacaga cacagcaaca atctgatttc 27180 tctatctttt ccccacattt cccccttttc tattcgacaa aaccgccatc gtcatcatgg 27240 cccgttctca atgagctgtt gggtacacct cccagacggg gtggcggccg ggcagagggg 27300 ctcctcactt cccagaaggg gtggccgggc agaggcgccc cccacctccc ggacggggcg 27360 goggctgggc ggaggcgccc ccaccaccct cccggatggg gcggctggcc gggcgggggc 27420 tggcccccgc ctctctcctg gacggggtgg ctggccaggc gggggctgcc ccccacctcc 27480 cggacggggc ggctgccggg cggagatgct cctcacttcc cggacggggc ggctgcgggg 27540 cggaggggct cctcacttct cagacggggc ggctgccggg cggaggggct cctcacttct 27600 cagacggggt ggctgccggg cagaggggct cctcaattct cagacggggc ggctgccggg 27660 cggaggggct cctcacctcc cagacggggt cgtggccggg cagaggcgct cctcacctcc 27720 cagacggggt ggcggggcag aggcgctccc cacatctcag aggatgggct gcggggcaga 27780 gaccctcctc acttcctaga cgggatggcg gccgggaaga ggcgctcctc agttcccaga 27840 ctgggcagcc gggcagaggg gctcctcaca tcccagacga tgggcggcca ggcagagatg 27900 ctcctcactt cccagacggg gtggcggcca ggcagaggct gcaatcctgg cactttggga 27960 agccaaggca ggcggctggg aggtggaggt tgtagcgagc cgagatcacg ccactgcact 28020 ccagcctggg caacattgag cactgagtga acgagactca gtctgcaatc ccggcacctc 28080 gggaggccga ggctggcgga tcactcacgg ttaggagctg gagaccagcc cggccaaccc 28140 agcgaaaccc cgtctccacc aaaaaaatac gaaaaccagt caggcgtggc ggcgcgcgac 28200 tgcaatcgca ggcactcggc aggctgaggc aggagaatca ggcagggagg ttgcagtgag 28260 cggagatggc agcagtacag tccagcttcg gctcggcatc agagggagac cgtggaaaga 28320 gagggagagg gagaccgtgg ggagagggag accgtgggga gagggagatg gagagggaga 28380 gggctaattt ttgtattttt agtagaaaca gggtttcacc atgttgggca ggatggtctc 28440 gatctcttga cctcgtgatc cgccctcctc ggcctcccaa agtgctggga ttacaggtgt 28500 gaggaatttg tatttttgag ttgttaatat tctggagctt ttaaaatgga ctatttattt 28560 gtttgttttt ttgagacaga gtcttcctct gttgcccagg ctggagtgca gtgctgcagt 28620 cttggctcac tacaacttct gccttccagg ttcaagcgat tctagtgcct cagcctcctg 28680 agtagctggg actaccacac ctggctaatt tttgtatttt tagtagagac ggggtttcac 28740 catgttagcc agactggtct tgaactcttg gecttaagtg gtccacctgc eteagettec 28800 caaagggctg gggttatagg cataagccac catgtccagc ctattttctt cttatttttt 28860 tgagacaggg tcttactctg tcacccagac tggagtgcag tggcacagtc tcggctcact 28920 acagcctcga actccagggc tcaagcgatc ctcccacctc agtctcccaa gtagctgggt 28980 ctacaggtgt gagccataat acctggctaa ttttaaaatg atgttgccca ggctggtctt 29040 aaactcctgt gctcaagcaa tcctoccacc ttggccttcc aaagtgttgg gattacaggc 29100 atgagccact gtacccggcc tgaaaabgga ccttttaata tattgatgaa ggagttcttt 29160 cagaaaaggg ggatattctt gctgaagacc aattgcttgt cttcttttca agtaagaaaa 29220 acagtaagac tcaaaaggaa gagaactttg accgcaatct gctttttttc tttccagagt 29280 tgaaaatatt acccaggtag tctgtacgtt gctgagtaac agacaatttg ataaaggagc 29340 ccaatgaaaa aaaaatgatt tgattgtgtg ggtgcccaga tttaatatca tttatttatt 29400 ttctttcttt cttttttttt gagactgatt ttcactcttg ttgcccaggc tggagtgcaa 29460 tggtatgatc tcggctcacc gcaacctctg cctcccaggt tcaagcgatt ctcctgcctc 29520 agcctcccga gtagctggga ttacaggcat gcactaccat gcccggctaa ttttgtattt 29580 ttagtagaga tggggtttct ccatgttggt caggctggtc ttgaactgcc gacctcaggt 29640 gatccgccca cctcggcctc ccaaagtgct gggattatag gcatgagcca ccacacccgg 29700 cccatttctt tttcttattt gtttgttttg ttaactaagt tttttcttta attgggaaag 29760 taatataagt gtattttatt acagaaattt caggctgggc ctggtggctt acacctgtaa 29820 tcccagcact ttaggaggct gaggtgggtg gatcgcttaa gctctggaat tcaggaccag 29880 tctgggcaac atggcaaaac tccatctgta caaaaaatgt tacaaaaatt agctggaagt 29940 gctggtgtgt gcctgtagtc tcagctactc gggaagctga ggtgggaggg tggtttgagt 30000 cctggaagca gagattgcag tgagccgagg ttgcgccact gctctccaac ctgggcgacc 30060 ttgcctcaaa aaagaaaaac aacaaaattt caaacagtgc agagttatat atagtgaaag 30120 cacatcttcg ttttactttg gaccttcaga actccttttt ttttttttga gaggagtctc 30180 gctcttgttg cccacgttgg agtgcagtgg ttcgatctct gctcattgcg tcctccgcct 30240 cctgagttca agctattctc ctgcctcagc ctcctgagta gctgggatta caggcgcctg 30300 ccaccatgcc cggctaattt ttgtactttt agtagcgaca aggtttcgcc atgttggcca 30360 ggctggtctc aaactcctga tccactcggc tcggcctccc aaagtgctgg gattacaagt 30420 gtgggccact gcccccagcc tggaccttca aaactcttta gacaactaca gtttccagtt 30480 tgttgagtat ccttccaaaa atagtatata tagaattgta tataaatgtg tatgtgtgag 30540 catacacaca cttatctcct cagttttttt tacacaaagg atgtccatat tgataaattg 30600 cttgccattt tttagtttta tattgcttca tacagttaat agcatctatc ttcttttttt 30660 atagtaacat ttaaagttaa ggctcatatt tctggctact cactagatga actttgccaa 30720 atactcttga aaacaacaac cgtgacttgg ccatcataaa gaaatagttg caagtggaag 30780 tataattctc taagaggtct cttgagactt aatgagtctc agtaaatgtg aagaagggaa 30840 gagatttcaa tttctggaga agatagactt tttcaaacag ctttattgag aattcctcct 30900 attgagaatc ctgaattata atgatacatg ctattagtgg aacttcactg tgtgtatgaa 30960 agatatgagg gtaaccacta gtcttttttt atacccgtga attagctcta accctgagtc 31020 attgcttcca taaeatccag tagtcacaac tacatgcaça tccaaagaga ggttcçtttg 31080 tccttttcct aaccataaaa aaagactatc atagtttatc ttaccaagtc gggttgttgt 31140 gcctgagaaa agcactgccg aattcccttt cccccttctt tttttttttt tttttttttg 31200 agacggagtc tcgctctgtt gccacaaatg cagtggtgtg atctcagctc actgcaacct 31260 ccgcctccca ggttcaagtg gttctgctgc ctcagcctcc gaagtagctg ggactataag 31320 cacgtgccac cacacccagc taatttttgt atttttagta gagacggggt ttcaccatgt 31380 tggccagagt ggtctggatc tcttgacttc gtgatccgcc cagtgttggc ctcccaaagt 31440 gctgggatta caggcgtgag ccactgcgcc cagcctcccc cttctttttc tgggtatata 31500 tatacaaaat aatcgaaggc agaatcttga agagatattt gcacactcat gtttattggc 31560 ccattttgcg caatagataa gaggtcgaag taaccgaaat gtccactgac agatgaatgg 31620 ttacagaaaa tgtagtatgt acatacaagg gaatattatt cagccttaaa aagaaagaac 31680 ctgtcatatg ctgcaagatg gatgaatctt aaggacatta tactgaaaga ataagccaat 31740 aacaaaaaga caattactgt atgattccac ttacatgagg tatctacaag tagtcaaatt 31800 catagacaca gaaagrtaaaa tggtggttgc taggggttgg ggrtgaaggag aaatgagaaa 31860 atggtgtttg atgagtatag agtttcagtt ttgcaagatg aaaaagttct agatatctgt 31920 tgcacaacaa tgtgaatatg gttagcacfca ctcaactgta cacttaaaaa tggtatacag 31980 taaattttat gtgtttttta ccagaattaa aaaaaaaccc aaaactaacc ccttacttta 32040 gaattgtgct gacaggccag tcagctgtgt tgtcattaga tcatcatctt tttttggtgt 32100 gtctggtaag ggtaatggaa ataccagaaa cctgacaaat aatagrttgtg ggtcttttaa 32160 gttctatggg gtgctgctgt tatttctatc actttgtgat gcttttccat tggctttttt 32220 tctattgaat attttcaccc ctttctagtt tacttttcag agtgaaatag atataacaag 32280 tgtaatgctt tgaaacaatc ctttttctct ccttcaggtg tgatgatgat cagatgtcta 32340 acgataagga gcggtttgcc aggtaatatt gtagtaggta atatattgta atatataata 32400 tgafcccatgt tgtagaacca gacagtccta gcatattgac ttaatttttt ctggatgaga 32460 eggaatttct ctgtttaata tctttcctat ttggaagtat gtgaaactta gtattataac 32520 tatcatttat gttcaggtga catggcttca aactggcggt atattttata cagtgttttt 32580 ctgtgtatgt gataactaaa gcaatgtgct tgcaaggttt ccataggagc acaaattatg 32640 gattttgtgc ttgcatttat tattaaatgg atctacaaaa ataggaatac agataatggt 32700 tctgtaatta atttatttat tttgagacag agtcttgete tgttgcceag gctggagtgc 32760 aatggcgcca tctcggctca ctgcaacctt cacctcctgg gttcaagcga ttctcctgcc 32820 tcagcctcct gagtagctgg gattataggc ccctgccacc acgcccagct aatttttgta 32880 tttttagtag agatggggtt tcaccatgtt ggtcagggtg atcttgaact cctgaccttg 32940 tgatocgccc gcctcggcct cccaaagtgc tgggattata ggtgtgagcc accgcacccg 33000 gcctatttta tttttttgag acagagtctc actccatcac ccatgctgta gtacagtggt 33060 gtaatctcgg ctcactgtaa cctctgcctc ctgggttcaa gctgttcttc cacctcagcc 33120 tccctagtag ctgggaatat gggcatttgc caccatgcct agctaatttt tgtaataatt 33180 ttttttagca gagatggggt ttcaccatgt tggceaggct tgtotcgaac tectcaacto 33240 aagcgattca cccacctcag cctcccaaag tgctgggatt acaggtgtga gccattgtgc 33300 ctggcctatt attttatttt aagatatgta tattttttag agacattgtt ttcattgtgt 33360 ttcccaggct ggagtacagt ggcatgatca tagctcactg cagccfccaaa ctctggggtt 33420 tcagfcgatcc tcctacctca gcttcccaaa tattgggatt atatgcatag ccaccatgcc 33480 tggttggtcc tgttttttta aaaatgacag taagaggcgg ggagtggtgg catatgootg 33540 taattccagc actttgggag gcagatgcag gtggatcact tgaggtcagg agttcaaaac 33600 cagcctggcc aacatggtga aaccccatct ctactaaaaa tataaaaatt agccgggcat 33660 catggtgggc actcataatc ccagctactc tagaggctga ggcatgagaa ttgcatgagc 33720 ccgggaggtg gaggttgcag tgagcagaga tggcaccatt gcactccagc ctgggtgaca 33780 gcaagatttt gtgtcagaaa aaaaaaaaaa agacagtaag gaaacagttt ttgtgacaag 33840 tagagttttg attgaaaaaa acttaaattt gtttaaatta cctatcaaga tgatgaaata 33900 tacttttttt tattaaattc ttaaatgtca gttttctttt tagaaagttt ttattaaata 33960 ttaggcaata aattatttct tttttgaaaa ttaagtttgt agctacctca gaaagatgaa 34020 taattcgtta tttcaaaatc cagtgattaa ctgagcactt agcacttagt atttgttcgt 34080 tgctgatgct cctggtctcg ggaacatact ttaagaaccg ttgatgtaga gagattagaa 34140 atatcagggg aagtagttaa aaactattct ggagtggtga gatgcaatct caggctttga 34200 attagagggt attacataaa atgcattgta gggatatttc tctggtagca gttatagaat 34260 tgattaaagg gatggactgt tagactgtag ggaggtagat aggaagctgt tgaaataata 34320 agacagctat aaaatcatga gggcctgggt tacagtggca gtggtaacag gaaaggagtg 34380 aagttaagag gtttttgaag aataatttgt ttatcgaaac taattgaaat aaatatttgt 34440 aaagtcttta ggatgtgaac catctctaaa atgagaagtt aatcatagat atttggagga 34500 tagtttttca agcttcattg aaaagtcagg ccatcagtta ttattggcag tatcttgatg 34560 aaatttcaaa aagccatgaa aacatcgcat gaatgatttt ggttttcatt tgtcctgctt 34620 aatgtgcata tatttcattc agaaatactg aggtggatta gggattgtgg atctgtagta 34680 gtagtagtag tagaaatagg aattttagat gcttaacttt tttttaaata acagaattca 34740 ttcatatgat gtgttaaggt agtgoccctc acatatcctc cttgggatat agagggtctt 34800 aaaagctgaa aacttcttga aaaacttttg ggattatatg catagccacc atgcctggtt 34860 agtcctgttc ttttaaaaat gacagtaaga ggccgggagt ggtggottat gcctgtaatt 34920 ccagcacttt gggaggcaga ggcaaaagtt gctcaacttt ttgaaaaaaa agaagtttgt 34980 agtttgttaa ggaactatct agaagaaata acccaaggaa tgtaaaactc taaactgctg 35040 aatatcactc agttctcctt ctcttgtcat cagaatatat gcgtaaattt ttacattctt 35100 cttcattgtt actgtgttat tttctgcota ttgaccattt tataaaaaca ttcccatata 35160 ttgataaggt tattgtattt gtcattttta atagctaaat aatcttttag cttgttaacc 35220 tgtcatactt agacatttta ttcagggcct ctttatctat ataaatatat ttaaaatgga 35280 attgacaoat tcctgacaca atggcotgec aacaccttgc tatttootoa gttgccaccc 35340 atcattacag tatctcagtt ttctagaaaa atttagtgat ggttctttgt atccttctcc 35400 agtggagagg gaattgttac ttttgateea ttcctgtgtg gctabactgc agagaaatgg 35460 caaaaggacc gaatcaaagt taataattat tttaggaaca aatcaataat agaagatatg 35520 ccagaaacct acctcttaga gttatttata taatttctcc agtgaaatct ggttggttat 35580 tttgtcattg tgtggcacgt gcatgtgttg tttgtçftgag agggagagag attatatttg 35640 tcatcaottg tttgatagta tcatctttaa tgtactctgt ctttaatttc ttcattatag 35700 aatagcacat gtggatatca ttttctttcc agattgggag cagtgcatga aaatggtatt 35760 cctgaattcc cttggttggt tcttgttcag actctgtata tctttggtcc ctacagagat 35820 cgattggcaa aatgctttct gtgtttagat catgttaatt tactatatat tggctttgct 35880 tttatgttga cotttatctt gtaagttact ttttctttat cctaacagat ggctttgtag 35940 agttacaggc aaggttcctg cctataattc catttccctc ctctcttctc tgcatctgtt 36000 tagttctata tccttttctc tcttctttct ccttttcttt ttttttctcc ctccatttcc 36060 tctccctccc tccttccttt tttcccttcc tccctccccc cttccttcct tcttttttat 36120 tttaatttta gcttagttca ttaattctat ttttaggtcg gatgatgagc agagctctgc 36180 ggataaagag agacttgcca ggtaggagaa cagtgtcttt tagcatgatg aagcagatga 36240 tgctgctttt tctatccttt ttcttactct ttcttttctt cccctttctc tttgtatttt 36300 tccttatctg tggcaagaga ggacaagatt ttttagaagt ttgagtgtaa caggaacttt 36360 ggcttccccc atcagaaagrt gggtgagttg agggaacttt gcttagggat ttaagaaatt 36420 gctattagtt ttaagttttt ttttcttttt ctctttatgt cagtactaag tttcacagaa 36480 caaaaagctc ttagaaggaa tgcaaccgtg ccagttggtg ctttaacagg gaaatactct 36540 ttttatcaga aaaccaataa atatatctgt atttgtgatt agttcccagt atttaggcct 36600 cagcatttac tccacacctc taggaaactc acacctattt tcctatgaag actcacagcc 36660 tagattattc tcacaacaga actagtgttg ctttggtgac cgaatccttt cttgcggtag 36720 ttttctagaa aagttttagt ttccttgatg tggctattta aaagaccagg tttctgtact 36780 tacgtgtcag aaatctgtca gatactagga agatgagtgc tttatgtttg agaatagaat 36840 tttatgtctt aggcaaagtg taactaaata tgggcctatg tggtgagacc ctttttgcca 36900 tttagaaagg agactctaga attctcttgg gagactgttg tttgtaatgt agaaatgctg 36960 cagaagaaat atgcatagac ttttctgttt tctagtatct gtgatttggg ggtgacttag 37020 gaaatagatc attgatgcca atacccattt ttactatatt cccccttttt tctactattt 37080 cctctttaat ctgggtcaca aactcatttt gctgccagtt taactcgagc ttcttactaa 37140 ccctttcact gttcagaaaa tggatttggc atgatgtggt ggagaaaaca ttgtattggg 37200 aagagagcag cctggggaaa gtcacttacc tacttgacct ccctttgctc ttctcagaaa 37260 aaagagattt atgttagatt tttaattttc ttactttctt ttttttttgg acaaagaact 37320 tttgttcaag tagaattctt aagtggtaac agaaataaat aaaagagata aagcaggccg 37380 ggcgcagtgg ctcatgcttg taaccctagc actttgggag gccgaggcag gcagatcacg 37440 aggtcaagag atggagaata tcctggccaa cttggtgaaa ccgcgtctct actaaaaata 37500 aaaaaaaaaa aaactgggcg tggtggtgtg cgcctgtagt cccagctacc tgggaggctg 37560 agatagcaga attgcttgaa cccagaaggc ggaggttgca gtgagccgag atcccgccac 37620 tgtactccag cctgggtgac agagcaagac tccatctcaa aaaaaaaaaa aaaaaaaaag 37680 aagaagagag ataaggcaaa tatttgagta gaagcagaaa tgcagcatgt tgcatgatta 37740 tctcettgag gcatccccat ggaggacact gagaaactta atgggctttt aaaaattcct 37800 gttggaaaac tgctggatta ttcctgttaa cagtgatatc tttctgtctt aattttgagg 37860 aagtcagtgt tggagctgtg gtctatttac ctgggtgaga ttcaaattgt cttgtcagac 37920 ctttaatcat cctcctctcc attccactcc tccagttaac ttcgtcccag actggggacc 37980 catatgggac ttttagtaga tggtgtatct taagtcttgt aagaagttta gtgcactggc 38040 agcacaccca gataaagaag gtaggacttt gtgcattaat gggccaaata aaacttcaaa 38100 atcttcaaat tctgcctttt aatgttgcaa ataagagaga ggcttaccat attttataga 38160 ccaaggaaat ctgtactatc aattcttgta tcagctatgg agccacatac ttgagttggc 38220 aaaaattggt ccttttattt tctggccttt aaatagttga attagtaagc atgggagtta 38280 accaagctga ggttatatgt tccataggaa cttaagtgag taaaatcagc atttaaaaat 38340 actatctttt tttttctctt gttttttgtt ttttgttttt ttttgaaatg gagtcttgct 38400 ctgccaccca ggctgaagtg cagtggtgtg atctcagctc actgcaacct ccacctccca 38460 gattcaagtg attctcctgt ctcagcctcc caagtagctg ggattacaga tgcatgccac 38520 tgtgccctgc taatttttgt atttttagta gagacaggat ttcaccatgt tggccaggcc 38580 ggtctcaaac toctggcctc aagtaatcoa cctgcotcca tctcccaaag tgctgggatt 38640 acaggcatga gooaccatgc ctgacctgtc gtttcttaaa acagottttg ttctgaggga 38700 gtggtaattt acaaaggatg tgaagtttcc aggaaatagg gggaagggaa ttacattate 38760 ttcttgttct ctgtctgcct tattagttct gtttcatgct tgctttgoat gagaaggttg 38820 gcaaacctta ttttaactgc tgagacttaa gcatcactaa atctgaatac cacattcttc 38880 agcagcacac ttggtatcca tatcactctc cctgctacca aatgaccaga tgtgaccacc 38940 tggatggggc ttctctttct ttccatgcag ggaaaatcac agtgaaattg aacggcggcg 39000 acggaacaag atgacagcct acatcacaga actgtcagat atggtaccca cctgtagtgc 39060 cctggctcga aaaccagaca agotaaccat cttacgcatg gcagtttctc acatgaagtc 39120 cttgcgggga actggcaaca catccactga tggctcctat aagccgtctt tcctcactga 39180 tcaggtctet gggacttata gttetgagag agtctggaat ctgggtgaat ctcttgaaag 39240 ttttcgtttt ttggacaaga attcagcttt tcaggaagaa gtcagacaat gggaaaacga 39300 atttcaatcc ttggctataa cattaattag cattgggaca atgagaagta gagaagagtt 39360 gtgaaaacta tttaataagc taataagtat taatatttga gaacttgact catgaatata 39420 gcatatagga tggaagaaga acagtggaat cacagaggaa atgactatgt ccatggaacc 39480 aattttcttt cttgccttta gggttataga agatggaaga aatctatttc ttatccctga 39540 agcagcttct agttttagta atagaatgaa tctgtcccac ctttggtgat agaagaactg 39600 agagtctaat tgttgcttag ggatgtgctc tgttacatgt gatcactatg aaaaaaagaa 39660 ggcgtaaaca ttttctgcct ttcaggaact tcatctgaat ataagtatgt gagtggcagg 39720 atatcacaga aaataacagg aaaatgcata aagagaggaa ttgtattttt taattagtaa 39780 ttttatgtgg gactagatag acatactgaa gggatggcta aagtgaatag aatggctaga 39840 cttgagtgag gatggttagg gaagacttct gagggtaagg aagccatgtt ctgttttggt 39900 tattaaaata acatgatcat tgcagaaaaa tttggaaaat gtaggaggta taaggaagaa 39960 aaaaatttac ttcagtatca atcaagtatt cccttaatgc caccaattta atcaaatgat 40020 tagaaagaag gagagaatat agtttgagaa aatggaataa gaattttcca aataggatgg 40080 tctacttaaa actacatact ttgtagctat atacattgaa atagttaata tgttctaaca 40140 gtacatgtgc aagtattcaa cagactccag ttatgcacct tttgtgggca aaccaggtgt 40200 gttgtgctgt gagaaataga aagaatggtg agacaaatgg ttttctggtg gaaacagaca 40260 tgtaaataaa taaattaaac atagaactag ttctataata gaagtgctgt aatgaatcct 40320 gtaaaatgca gatatggaaa atgagttggg gagtagtgtt gtggattttg ggaagcactt 40380 gagcaaaaac ctagaagtgt ggaataattg ggttatgcaa agaaagtcaa gtggtttagc 40440 atgtttttgg tagataatag gaaggtaggc tgggatctaa tgatggaatg tttaggtgtt 40500 aaagaattta gattttaatt tttatgcagt ggggagacat aaaaaatgta ttagatctgg 40560 tagcatttta aggattgatt gaaagcaggg cgactactta attagttttg gtaaaagatg 40620 actaggacag tgacaaagca ttggaaagta gaatcgataa aactgaatta tcactggaat 40680 gtgagagaat agttagattt tgaggcttct agcttaggag gatgctgtta agaatattgg 40740 aagagcacgg caggtttttt tttttaagag ggaaataatg attcaggttt tgggatgttg 40800 atgttgagtt gctggtagaa tatttataaa tattttacag atacttgaaa ttcaagtctg 40860 ctgaaagctc aggaaaaaac gttagtcatg tctagggcta tagacttggt tattatttcg 40920 tagtggggaa gagtgaatat ggtttcccag gaagaaagta tggtattaat aaagagggct 40980 taagatgaac tttggaaatg tctacattta agacttgaac aaaggaaagg aagtctgaaa 41040 cagaagagga agcaaaaatt ggagtacagt ctcatagaag aaggtaggga aaaataaaat 41100 ttaaaggata agatggacga cattgrtcaca ttctgcagag aggttgaata aagrtgatgaa 41160 gacccaggaa aagggacttg aattggtaat taggaggaca ttagtaacct cattaaaaat 41220 atatgtatgc tgttcctggc agaacaaaaa ccaaaccaaa caggaaaaca gtagtttaga 41280 gtgagagtga agtgggattg agaaataatt gaaaggtaag aggataaagc cagtgaatat 41340 aacattattc ttagtataag cttgctgctg aaaaagagag atgaggtggg tcaaactgag 41400 ggaagattta tctagaattg agaaaacttg atcattttta taggcctgaa gggaaagaga 41460 gaaagtggga atatttgtca agcaagatcc taaaaagaga ccagagagga tggaattaag 41520 aagtcaatta ttgttcatgg taagcctttt tttttttgag acagggtctc ttgctctgtc 41580 gctcaggctg gagtgtggtg gtatgatctc ggctcactgc aacotctgct tcccaggctc 41640 aggtgatcct cccacctcag cctccggagt agctgggact acaggcgtgt gccaccacac 41700 ctggctagtt ttgtttttgt ttttgttttg ttttgttttg tttgtttgta aagatggagt 41760 ttogcoocat tgcctaggct ggtcttgaac tcctggactc agtgaccctc ccactttgac 41820 ctcccaaagt gctgggatta ccggcgggag ccgctgtgcc tagcccaagc ctttttattc 41880 ttcttgaatc ctgagataga gaggaagagg tggatagtga catagagaaa gtgaggaaac 41940 atgtattaga aaaaactttc ttatcgatga actacattta gggtggaaac ctgtggctgt 42000 ggatcaggtg tgaaccagca gttgcttacg gagagatgca tgtggcctga agtgtcttac 42060 ttcttcctgt gaatagaaat acttgttttt tcagagtaaa atattaactt ctatttcttt 42120 ttcttgcgca ggaactgaaa catttgatct tggaggcagc agatggcttt ctgtttattg 42180 tctcatgtga gacaggcagg gtggtgtatg tgtctgactc cgtgactcct gttttgaacc 42240 agccacagbc tgaatggttt ggcagcacac tctatgatca ggtgcaccca gatgatgtgg 42300 ataaacttcg tgagcagctt tccacttcag aaaatgccct gacaggtgag agttatgtgt 42360 atgggaaatg aatgagaagt cctttcttgt ttttttcctg agacttaaga gatgttttag 42420 ctgttaaatt ggtttgttga ctctggcaag gcttcaagaa ttttctactt taatgaatat 42480 agtcagttct ttttatccat atgagattat ctactttgtg gctcagcctt agaaaatatt 42540 tcattggtga taatatttta catttatctt aatattggta taaatagaac agtaaaagcc 42600 aaacctacaa tacttttttt tttccgttct aaaagaatta tccatgtttt tatctcattt 42660 gtatggataa ttatctggta ttttttctac ctcctggtgc ttggctttgt gctaggttca 42720 atgataacag ctttttattc tatagatatg gttattggtc aatgtataag gtgttttctg 42780 ttgttgttgt tgttgttgtt tgtatctgta ctgttgttct ttttttctcc cctattttat 42840 tatgttcagt cttttggcca gagtttggct agaggaaaca agtcatatct attcttgagc 42900 aactctagaa aaaaatttaa agtggaagca gataaaaaaa ctggtagtta aaatgcaaga 42960 aatttcaata tactcatatt agtgttgttg atctttaçrtt ttcctccttt tttcccaccc 43020 aaaaaagaga cagggtctct ctcttgccta ggctggagta cggtggcaca tcatagctta 43080 ctgtaatctt gaactcttct gggctcagta atctgcctgc ttacagcttc ttgagtagct 43140 aggagtagtt catgtcacca cacttgacca atttttaaat tttttgtaga gacaggttct 43200 gtctgttgcc cagactggtc tcaaaotcot ggccttcagc attcctccto ccatcttggc 43260 ttctcaaagg gctgggatta tcggcatgag ccaccacact tgaccagttt tcccctcctt 43320 tatgttttta tgatttcatt tttctagttc ttccttttcc ccaaaagttg ttcttcgttt 43380 ctgtataata aagaagacaa acagatctat atgtttctat aacatataaa attacttggt 43440 ttttttcttt ttaaaatttt ttctttttat tctttttttt ttttttgaga caaggtcttg 43500 ctttattgct gaggctagag tacagtgact cttcacaggc acagtcatag cacactacag 43560 cctcaaactc ctgccctcaa gcagtcctcc tgcctcagcc tcctgattag ctgggactac 43620 agaaaagtac ttgtttttca accaatgaca tttactctgt atgtatgtct gtatgtgtat 43680 acagataatc agctatgaga atatagcctt gcctcttgtt ttctactact actttccact 43740 cctacttttc cttgcacaat gttattttca atgctgcctt tgaacttaag agtgagattc 43800 attgatgata attgaagtat tttaggcttg aaaaaaaatt catctcctgc ttggtcagtt 43860 ctgttataag caaggagatt aagggcatga ataggatgct tacttatctt tgoottcagt 43920 atctctcccc ctcttcccca cacacaaaaa tgcactccag actgctcttc acatcttcct 43980 tcagggcgta tcctggatct aaagactgga acagtgaaaa aggaaggtca gcagtcttcc 44040 atgagaatgt gtatgggctc aaggagatcg tttatttgcc gaatgaggtg agtgtcaagc 44100 tgaggattgt gatttggtat aggaaggatc aagagctgag agttttattt ctgtcagagt 44160 fcaagttggat tagctccagt ggattaaatt taactctcoa tacccagatg gattgtaaca 44220 cagaataaag tatttggaaa gggaactaac gtttctgaac ttgccagaca ctatgatagg 44280 tgctttatat ctgtcatctt attttatcct cacaattgcc ttgtagtgta agattgatgg 44340 ttaccatttt gcagatggaa aaacagatat aaagaaatga acttggccag gtgcagrtggc 44400 tcaaggctgt aatcccagca ctttaggagg cfcgaggcgag tggatcacct gaggtcagga 44460 gtttgagacc agcctggcca acatggtgaa accccatctc tactaaaaaa aaacaacaac 44520 aaaattagac gggcgtggtg gcgtgcgcee ataatcccag-ccacttggag gctgaggcag 44580 gacaatbgct tgaacccagg aggtggaggt tgcagtgagc cgagattgtg ccattacact 44640 ccagcctagg caaaaagagt gaaactctgt ctcaaaaaaa aaaaaaagaa aaagaaaaag 44700 aaatgaattt cccactgtta catactgttt gatacaggat tttgttttaa ttcatagtag 44760 tctgactaca aaacctctac tttttccctg ttacaacaca aggcaatatc catttactca 44820 gaccafcbtct tctttttttt tttggttaga aatttgagac ttcctatgtc tttcagtagg 44880 tgtttagtgt ttataaatta tatactgtac gttttaggat tctgtagaaa atatggtggt 44940 cctttctata caggtacaaa aggcatctca gggtcacaaa gttcaggcta tataatggaa 45000 attgactaca ttgtactgag aggatagttg ctagaaatta tgggtaggat attaaaggtt 45060 tgcttggaga ggcacaaaat tgaacattat gtggtttagt gatttatttt tatttttatt 45120 tatttatttt tttgagacag agtcttgctc tgttgcccag gctggagtgc agtggcatga 45180 tcttgggtca ttacaacctc tacctcctgg gttcaagcga ttctcatgcc tcagtttcct 45240 gagtagctgg attgccacca cagctggcta atttttgtat ttttagtaaa acagtgtttc 45300 accatgttgg ccaggctggc ctcaaactct tgacctcaag tgattcgect gcgtcagcct 45360 cccaaagtgc tgagattaca ggcctgaacc actgcaccca gcgtgtaatt tagagtagct 45420 tctagaccca gactgctgga ttttgtttta atccatattc tatggatttg aattctagct 45480 ttgatgctat cttctgaaac cttggatgat tacatgacta cattgtgctt tgatttcatc 45540 atctcacatt ggcgataatg ttaatactga ctttataaag ttgttatgaa gattagatga 45600 attaatatat gtaaagatat ttagaacaga gcatgacaca tattaaccct atgtaagttt 45660 tatttttgtt ttaaaggata gggagaggga aagtagcatt ggcaggagta tcccaatatg 45720 tggacatggc taatgcaaag acataggcaa gagcaagata ataatgaact gtagcaatta 45780 cattaagttg tggttaatgt agagcaggag taagcaaacc acagcccttt atttgtaaat 45840 aaagttttat tggaacatag ccatgcccat atttttacat attatctatg gctattttca 45900 tgctataatg ctagagttga ctagttgcaa cagactttct ggcccgcaaa gctgaaaata 45960 tgtactatct ggtcctttac agaaaaagct tgccaactct tgatgttgag aatgtttgca 46020 tatgaagaac atatggaaca ttttgacttc aaattctaaa agttttagaa atactaaact 46080 tgacctatct ttatccttca ttattagtag cattaccaat tttctatgtc tggttgtato 46140 cagagcatgt tattctgcta ttactgtgga aagttctttg atagggcagt ctgattgctt 46200 ttaatctctt tattccttga aacaggtgtg gcagtagctc tgtggaccca gtttctgtga 46260 ataggctgag ctttgtgagg aacagatgca ggtgagatcc taagtggtga aaaccaaagg 46320 gatggccaaa tacctgcaga gatcatcaca tttttacctg tcttactgta gtcgttcctt 46380 cagcagctct cacttgcatc ccttacctcc cacttaacat cccttacctc ccacttactt 46440 tttttctggc aatattttcc taaacttcta aaacttctct tgaaaatcct gtttaaggaa 46500 gtcgctatgc tattttacct actttcctcc tactgcatac ettttggtta ctttactttg 46560 gcaagggtaa aaatgtggcg gtcatttttg ggtgggaaag atgattatcc tgttttctaa 46620 actcctaaga gcataaactt aaaagtacta aggcagcatt gccctttgag ttttacgggt 46680 agattttttt tttttttttc aaaotcctgt aactcttcta ggaatggact tggctctgta 46740 aaggatgggg aacctcactt cgtggtggtc cactgcacag gctacatcaa ggcctggccc 46800 ccagcaggta agaaagtgaa atagtaaata tttccccttg gtacagttgg ttcctcacag 46860 agtccatgaa agctaatatt tattatatac ctggtatatg aaatgtactt ttgtgtaaga 46920 tgaaagaaaa taggaaaaga aaatgtacaa tccttccctt ccattattga gcttttattc 46980 cagttgagga gatagataac tcaggctgga aaatgattca gtattggctg tgtcacagaa 47040 tgtggttttt atgtgaacaa atttatactg aacatatgta ttctaagcat ttgttgcaaa 47100 gaaacttaga cattgaatgc agttaatttg agaaagattt ctaaagtagg aacaagactt 47160 tgagagaaaa ggggaaaatg cctttattgt aataacttat caagaggata ttctctgcaa 47220 agactttaaa tcaagctttg agcagattag ctttaccaga acttgaggtc aaacaaggaa 47280 tgtgagaaag gtgattgggt tgcaggatca aagttttaag ttggcttgtc agagtttcca 47340 aatcttagca actttattac ttccctgctg cotgggtatt attggaaagt aggggttttg 47400 gggagacaga aactaagaga aaagagaagc aaggtgatgt gttttggaaa aagçrttaaac 47460 tttggatgtg gagaaacctg gatgtgattc ctgtcattgt tacttattag tggcatcacc 47520 fcagggtaagt tgcttgacct ttataaagct cagttttctc atctgtaatt cagagttagt 47580 acatcctgta tagggttttt grtgaggatta gatttaatgt aaggaaagca tccagcccag 47640 tgcctggcat atggcaggta acccaataaa agtaattaat gtaatttaaa aaaatttaac 47700 tgaagtagta atgacatttg aactacttag tctatatact atataagcca cacagttaaa 47760 gtatgtgatc tttcatacct ctatgtagca tcaaggaata ctatttttct ggataaaaag 47820 agtataacta tgcaaaaaac aggggagaaa tgcagtcttc ttccctttct gtgtaaaaca 47880 ttggtttttc tcttttccaa gggacatgaa taactattga tggttggtat aacttoattt 47940 tgggttgctt gctaacttta aaagttacag attaggcaaa gcataaattt tctgcctata 48000 acatggtcat agaatggabg tcttcatatg tgccatattt ggccagcata gttttttaga 48060 gtactctggg taggacttgt attttccagt ttactataat taacatgggt aaaatgtagg 48120 aattaatata tatgtaaata cbtaaaacaa tgactggcat atatggtaag ttttatatac 48180 ttgtttattc ttatttatea ttototattg ctttatgott agcctcttoa taactagatg 48240 tattttgttt tgttttgctt tttggttttt tttttgagag ggagtctcac tctgtotgto 48300 gcccaggctg gagtgcagta gtgcgatctc ggctcactgc atcctccgcc tcctgggttc 48360 aagtgattct ctcacctcag cctcccaagt agctgggatt acaggtgcat gccaccatgc 48420 ctggotaatt tttgtatttt tagtagagat ggggtttcac tgtgtoggoc aggctggtcc 48480 tcaagtgatc cgcccacctt ggcttcccaa agtgttggga ttacaggcgt cagcoacggt 48540 gcctggccca taaataggtc tattttgaat ctttacttgt ctgagttttg aaggcatttg 48600 açrttggaggt ccccgttaaa ccttttaacg tcacgtttct gaaggtgttt ccctcccaga 48660 fcgatgaccca gaggctggcc agggaagcaa gttfctgccta gtggccattg gcagattgca 48720 ggcaagtatg aattttccac atctatattc ccgttcaatt agagcagatc ttcaggactc 48780 atfccctgtta attttctttt actttctgaa tacaaatgaa gaattccata aaactctcaa 48840 aatttgaagg aatatggcat ttatagtgac cattgctatt cttggattta agtaaagttg 48900 aaaagtatga gaggagggag atctttttcc ccttgtctta attttagctt tactatgctt 48960 aattttctat ttccagttaa tttcctttgc ccctatacaa aagaagaaag atccttttca 49020 ttgtatcatt acctgactaa caatagaaaa gtggaattat tttgattttt tcataagtat 49080 agataagttt cttggttact tgtaccatat caacctgagt aatgagttca gcatagccag 49140 tatgtggatt ttagattgaa taaactttat tcttacttta ctaacttggt aaagtgtaaa 49200 tgtatgggag cagagctaga ccttatgcct tgtctgattg tgattgtcat ttttttttco 49260 tttttggata aaatgtgaaa gtttagaaag tcctaaaact gggaatctta tgtctatgca 49320 aaagaccatg aggagatagg aaatacatct gtaaataatg gtatcatttt acctcatttt 49380 tatctcttca ctctcaggta actagttctc ccaactgtac agacatgagt aatgtttgtc 49440 aaccaacaga gttcatctcc cgacacaaca ttgagggtat cttcactttt gtggatcacc 49500 gctgtgtggc tactgttggc taccagccac aggtgaggag ctggagctcc attaggcctc 49560 cattttcctt tggctatgtt gacattatgt aatcatgtag ttoctaagac agccaaaaca 49620 tatcaacctc agttgagaaa aagagatcat catattctgt tagtacctaa cattattttc 49680 agcttcctat taggactgtc atctcatgta gagaaatatg gcttgtcaaa ccaggtggga 49740 gcagcaggta caaatatgta tttatttttt gttgttgata ttaatacaga tgattcaaag 49800 gtactcatat taattagtta taccagtata gctacattta gataattcat gtaattacct 49860 aaatgaataa tggcccataa aacatgcaga tttagcacca gttattataa tttactcatg 49920 caacagacca gttagccatc tctgaattga cgcatcatat aaacttttaa aactgttgtg 49980 ggtcggaagg acttctggct gtggctatgt gaaagaggtt ggtgaaaaag aggtcttgaa 50040 aacaaagaac aaagagaatt tacactacct gattcaacac taactataaa gctattacca 50100 agacactgtg gtgttggtgt aaggatagat atatagatca atagaccaga ataaggtcta 50160 ttcttatact tgtcaactaa ttttcagcaa aggtgacaag acaattcaat ggataaaata 50220 aatatttcta acaaatggaa caattggata tctgtatgca aaaaaaaaaa aaaacaaaaa 50280 aaaaaccaca cccaaaaatg aaaacacata gatcttacct catacaattt acaaaaatca 50340 gcttagaggc ctaaatgtgt aagagctaaa gttacaaata aactcctagg agaaaatctt 50400 tgtgattttg agttaggcaa aagatttctt acactaaaag catgattcac agaagaaaaa 50460 aaattataaa ttggatttaa ttgtaattaa aatttgccct ctttaaagga tattattaag 50520 aaaatgaaaa gaccagacat aaatggagag aaaatagtta caacftcatat acctgaaaga 50580 ggatttgtac caggaatata taaacaactc attaagacaa acagctggta aaaaagagca 50640 taagacttga catttgactg aagaataaat atgcatttat gcacatgaaa agatgctcaa 50700 catcttttta ccattaggaa agtgcaaatt aaaatcacaa tgagatacca ctatataccc 50760 actagaatgg ctgtaatcaa aaagtattgg tgaaaatgtg tagaagctgg aaggaaccct 50820 catacattgc tgatagacat gtaaaatggt atagctaeta gctttgcaaa agcattttgg 50880 cagtttccta caaagttaaa catactctta gcctataacc tagcaatttt attcctgagt 50940 atctacctaa gagaaatgaa aacatgttca cccatagatt tgtacacagt tcatatctgt 51000 attattcata atagccaaaa aaatgaaaac tatttaaacg tccattaaca ttttgtaaat 51060 gaatacacaa ctçrtgttgta tccatgtgag aatactactg agcataaaaa ggaataaact 51120 actgataatg cagccatgta gatgaacttc aaaaatacca tgctcaatga aagaagccag 51180 acccaaaaga ccacatatta tgttgtttta tttatatgaa atttgtagaa atagcagaac 51240 tagagaggca gaaagcagat ttgtggttgg ctggggagtt ggagtgggag cagagattga 51300 ctgcagatgg cacaagggaa catcttgggg cagtgaatgt gbfcctgaaac tggattgtgg 51360 taatcattgc acaactataa atttagtaga catcatcaaa tcatacactt agaatggctg 51420 aattatgaat gtaaatttta tctaaaattt ataatctcat taaaataaat gtataatatt 51480 ctgagaaaga aaaatgtttt agaagccagc tccttaacag attctgcctt tttttagtag 51540 atttcatctt ttgtttattg tctttttttt ttctcctcct cacttaacta taatcttagg 51600 attaaaacag aagaaataaa atccaggtcc coagctgatg gaccaggcca gttagatgac 51660 cataaaatta tatatgttgg ctgggcacgg tggctcacac ctgtaatccc agcgctttgg 51720 gaggccgagg ogggtggatc acttgaggtc aggagttcga gaccagcotg aooaacatgg 51780 tgaaaccctg tctctattta aaaaaataca aaattagcca ggtgtggtag cacacccctg 51840 taatcccagc tacttgggag grttgagacag gaaaattgct tgaactcagg aggtggaggt 51900 tgcagtgagc caagatcgcg ccatcgtact ccagcctggg caacaagagc gaaactccat 51960 cttaaaaaaa aaaaagtata tatcttactc ttctttctgt attctaggaa ctcttaggaa 52020 agaatattgt agaattctgt catcctgaag accagcagct tctaagagac agcttccaac 52080 aggtaacttt tttcctggtt tggttctgaa taaatatttg tcatattcac tccataaata 52140 ttgactactg attaactgaa cactgtggca ggcactacag ttttatgttc tttagtagtt 52200 aatctgcatt tttaaggaat agaaaaggac taatactttg aaattatgga taatgcccaa 52260 ggtatttctg tttggctttg gctatttact gtcttgtatt caattaactg tatccaagga 52320 gctgtcttta aggtatttaa actattgcgc caggcatggt ggctcatgcg cccaacctct 52380 gtagatgctg tgaaaataga tgttttcctc gtctgggcat ggtggctcac gcctataatc 52440 ccagcactct gggaggctga ggcaggtgga tcacttgagg ccaggagttc aagcccagcc 52500 tggccaacac agtgaaaccc catgtctact aaaaatacaa aaaattagcc tggtatggtg 52560 gtgcatgcct gtaatcccag gtactcggga ggctgaggca cgagaatcac ttgaaoctgg 52620 gaggcagagg ttgctgtgaa ctgagatcat gccactgtac tctagcctgg atgacagagc 52680 tagactctgt ctcaaaaaaa aaaagataaa aaagaaaatt gtatacttca ctaagcttgt 52740 agtagaaaaa ttcattttat atagtttttt ttttttttta gaaggagtct agctctgtcg 52800 ccagggtgga gtgtagtgtg caatctcagc tcattgtaac ctctgcctct taggttcaag 52860 cgattctcct gtttcagccc cccgagtagc tgggattata ggcacatgct gccacgccca 52920 gotaattttt gtatttttag tagaggcggg gtttcaccac gttggccagg atggtctcga 52980 tctcctgacc togtgatcca cccaootcag cctcccaagg tgctaggatt acaggcatga 53040 gccattgcgc ccagcctaga ctgttctttt atggatgagt gagagtcgta atgaattata 53100 taagctgact gttaattgtc attctcaggc tccagctcct gaaaatatct ggtgaatttt 53160 atagacatgg cttttgataa cggtttttac tttgtattag acaagttaat taacctcttt 53220 aagtctcagt agtgtcgtta ttgatacaat gaatatatta atagtaccta aattcagacg 53280 gttgtfcggga agattaaata aggtaatgaa tataaaacac atcacccagt atttgatacg 53340 tagtattaca aaataagtgg ttagcttcta atactgttta tttttatttt tttaattttt 53400 aggaatatag agttaaaaga ttattttcta ttccatgaga ctagtatcta aaataaccta 53460 aaattggctg ggcatggtcg ctcatgcctg taatcccagc actttgggag gctgaggcag 53520 gtgatcactt gaagccagga gtttgaacca gcctggccaa catcttgaaa ccctgtctct 53580 actaaaaata caaaaattag ccgggtatgg tggctcatgc ctgtagtccc agctacttgg 53640 gaggctgagg catgagaatt gcttgaaccc aggaggcaga ggttgcagtg acccaagatt 53700 gccccactgc actccagcct gggcgabaga gcaagactgt ctaaaaataa aataaaataa 53760 aaaataaaat aactaaaatt acttttaaaa aataaaagca aaacaagact aaagccaact 53820 taattttatt tatggaaacc tctgtagatg ctgtgaaaac agatgctctc atctgggtgc 53880 agtggctcac acctataatc ccagcacttt gggaggccaa ggcaggcgga tcatttgagg 53940 tcaggagttt gagaccagcc tagccaacat ggtgaaaacc cgtctctact aaaaatacaa 54000 aaattagctg ggcgtgatgg tgcacgcctc tagtccccag ctactcagga ggctgaggca 54060 ggagaatcac ttgaaccctg gaggcgaggt tgcagtgagc caagattgca ccactgcact 54120 ccagcctggc gacagagcga gactccatct caaaaaaaaa aaaaaagaaa aagaaaagaa 54180 aacagatgtt ctcaggtttc ggggaaaaaa taggattgaa gagcaatata taagctatat 54240 tctgtgtcct taaacttacc aaatttctgg tatagacttg taaagctagg tcagagtatc 54300 tttaatggat ttcccaaggg aagtagggaa acagtctttt ccttcctgga aataagttat 54360 tattcctatt tgactagaat agtattaggt tggtgcaaaa gaaattgtga ttttttgcca 54420 tttttttaaa tggcaaaaaa tgcaattact tttgcaccaa cctaataaga aagcttgagt 54480 ctctggccgg gctcagtggc tcacgcctgt aatcctagca ctttgggagg ccgaggcagg 54540 cggatcccga ggtcgggaaa tcgagaccat cctggccaac atggtgaaac cccgtctata 54600 ctaaaaatac aaaaattago tgggcgtggt ggcaogtgcc tataatctca gctaettggg 54660 aggctgaggc aggagaatcg cttgaacoag ggagtoggag gttgtagtga gccgagattg 54720 cgccactgca ctctagcctg gtgacagagc gagaotccgt ctcaaaaaaa aaaaagtctg 54780 ggcacggtgg ctcacacttg taatcccagc actttgggag gccgaggcgg gcggatcaca 54840 aggtcaggag atcaagacca tcctggctaa catggtgaaa ccccgtctct actaaaaata 54900 caaaaaatta gctgggcgtg gtggcacgcg cctgtagtcc cagccactcg ggaggctgag 54960 gcaagaaaat cgcttgaacc cgaggggtgg tggttgcagt gagcagagat cgtgccactg 55020 cactccagcc tgggcgacag agggagactc cgtctcaaaa aaaaaaaaaa aagcttaagt 55080 ctctgaaagg aagcatgaga aatatgcttc catgtttaat cacttagttt ttactctcat 55140 tttgttttaa tattgaaaaa tattggtgcc tcaaggacaa tgacaagagt tttagggtta 55200 tagaaattgg aaaattttta tttatttttg taatgaaaat tttctatgag ttccactgat 55260 ggcatgaaaa ctttttcagg tagtgaaatt aaaaggccaa gtgctgtctg tcatgttccg 55320 gttccggtct aagaaccaag aatggctctg gatgagaacc agctccttta ctttccagaa 55380 cccttactca gatgaaattg agtacatcat ctgtaccaac accaatgtga agtatgtatt 55440 atacaggagt gtgaaaaaac tgtttttcct ctgttctcac aacagaaaac acttctgatg 55500 ccctatgtgg ggggtaaaca atcaagcaac aacacaaaaa tttagccggg cgtggtggca 55560 tgtgcctgta gtcccagcta ctctggaggc tgagacagga gaatcacttg aacctgagag 55620 gtggaggttg cagtgagctg ggatcatgcc actgcactcc agcctgggct acagagcgag 55680 actccatttc aaaaaaagaa aaagaaaaaa gaaatcaagc aatcagtagt ggacaccagc 55740 tgggtgtcct tccattcaat tcagttcact atctacttgg agatagcatc agatccccca 55800 atttgtgtat gcagtaccac aagactgctc ccacttctga tgccagttgc aagccccagg 55860 ttgttttacc tgtgcatctg actgaccagc tgtctcccat gaccccctac ttgggttcag 55920 tcaatttgct tgaatggctc agggaacatt tacctatgtt taccagttta ttataaagga 55980 tattacaaag gatactttgt acatcagatg aagagataga tagggcaagg taaggaggaa 56040 ggagcgcaga gctttcagac cctttctggg tgggctaccc tccggggatc tccatgtgtt 56100 tacctatcaa gaagctcctc aaacccagtc cttttgggtt ttaatggaaa tttcattatg 56160 tagccatgag tgattaaatc attggccatt ggtaatcaac ttaaccttag gtaccggctc 56220 ccctccatga ggttgagggt tagggctaaa agtcccagcc ctctaatttt accttgatct 56280 ttccagagat gagcccccat cttgaagota cetaggggtt gccagccctc agtcaactca 56340 ttagcagaca aaaagacact tatcacactg aagattccaa agattttaat tggrtaaaaat 56400 ccaggtccac ttatacatgg atttttttca gtaaatatat tagaaaattc ttttgatatt 56460 tgtgacaatt tgaaaaaccc aaaaataagc tacatagcct ggatatattg aaaaaattag 56520 aaaaagttag ccatgtcata catgaatgta ttaaatatat ataaattcta gtctatttta 56580 tcatttacta ccatacaaca tatacaaatc tattataaaa agtaaaaatg ctggacaggt 56640 gcagtggctc acacctgtaa tcccatcact ttatcacttt gggataccaa gttgggatac 56700 caagttgagc agatcacttg aggtcaggag ttcgagacca gcctggccaa catggtgaaa 56760 ccctgtctct actgaaaaaa aaaaaaaaaa aaaaaagaaa atacaaaaat tagctgggca 56820 tggtggcaca cgcctatagt cccagctact tgggaggtta aggtatgaga atcacttgaa 56880 cctgggaggt ggaggttgca gtgagctgag atcgcaccac tgcactccag cctgggtgac 56940 agagggagac tccatctcaa aaaaaataaa aataaaaatg tatcacaacg tatacataca 57000 caccgtttgt acaatggcac catttgtagt tgagagaaat gtaaacaaat gtaaagatgc 57060 açrttttaaat cataaccgcg taaagttaac tatagtatat actgtactgt tgtaataatt 57120 tggtagccac ctattgctca attgttgcca gtttgcttaa aatgctgtgt gatgctaatc 57180 atctcttcat gagcaattca ctccagtaaa ttgcatattg cagtaaacag tgaaatctca 57240 tggttcttgc atatttttca tcgtgttgag tgcaatactg aaaccttgaa taacatttgg 57300 gaacagtatg aagtgccact agtgatgctg gaagtcttcc caagaagcag ggaaaagtca 57360 tgacattata agaaaaaggt gaattgcttg atatgtacta tagaatgaag tctgcagctg 57420 tggttgcttg ccacttcata tagatgactc atcttgtaag tcatcttgta agatgatata 57480 â^CttdtÇãt ââCÇâtã.S.ãt QCtÇtãâãtÇf CãtfcttCtCt tCCttetÇât 37540 tttcttaata acattttctc tttagcttta ttgtaagaat acagtacata atacgtacaa 57600 catacaaaac gtgttcaact gcttatgtta ttggtaaggc ttctggccaa cagtaggcta 57660 ttagtagtaa cgttttggga gagtcagaag tttacagtcg aattttcgat ggcacagggg 57720 tcagtgcccc tagcctccat gttgagcaat cagttgtatt tcataatatc acataggcat 57780 tttccaatgt tgggatttct aatgtaccaa ctcttcttag tcttatcaag ctatcccttt 57840 ctcctctact tttctagtat taaacaccat tagtttgaag ttcttcattt tccagcttat 57900 aggatttggg atagttgatc agagtagagt aaggtttttt tgttttgttt tgttttgttt 57960 tgttttttca gacagggtct cgctctggca cccaggctgg aatgcagtgg tgtgatcatg 58020 gctcactgca gcttgaacct cccaggctca agtgatcctc ccacctcagt cccctgagta 58080 gctgggacta cagacatcta ccaagacgcc tggctaattt fctgtattttt tgtagagatg 58140 ggatttttcc atgttgcaga gtctggtctt aaactcctgg gcacaagcag tccatcgtoo 58200 tcccaaagtg ctaggatcac aggcgtaagc cactgcacct ggccagagta agattttaca 58260 aacaataatt cagagactag gtcctgagat ggaagggttt agtttcaatt ctatgtatca 58320 actctttctg gaaaggacta tgttttgtac accagtttat tgctctagtc tggcaggatt 58380 ttcctctgga gcaggggtag gcaagctctt tetataagtg gggctagata gtaaatattt 58440 taggctttgt gggccatgtg gtctttattc cacctactca actctgctgt agcatgaaaa 58500 cagtcataga caaatgaaag aatggggctg tgttccagta aatctttatt tagaaaaaca 58560 ggcagtgggc ctgatttggt cagttttctt tagagcatag ctacatcctc ctctttcatt 58620 agttactgtt cctctctttt gcacttttct atttgagttt tctttctcag tttctttttt 58680 aaaaagtttt atgagatata tttcacatac catatacctc actcatttaa agrtatacagt 58740 çrttttttagt atatcacata gttatgtaac tcttactgca gtctaatttc agaatatttt 58800 cattccccca aaagaaattc tagatcagtt aacagtcatt ccctgttctt tcccccggct 58860 ctgaaattct gtataactat gaatctgttg tctttataaa tttgtctatt ctagactttt 58920 cgtataaatg gaatcataga ctttgtaatt cctttgtaac tggcctattt tacttagtat 58980 aatgtttaca gaggttatct gtactgatac atgttgtagc atgtatcagt acttcatttc 59040 tttttattgc caaataagat ttcattgtat ggatatacca catactgtct gtatgttcgt 59100 taatggacat ttggttgttt ctacttcttg gttatcaaaa atgcttccat atgtaaaata 59160 gggataagga actgaaaaaa tgctttcatg aatatttgtt tactagtttt tatgtggata 59220 tatgttttta ttctcttgaa ttccacceag gagtggaatt gctggccaca tagtaactct 59280 gttttacctt ttgaggaact gccaaactgt tttccaaagc tgccccatca ttttgcattc 59340 ccaggagctc tgattcctcc acatccttgt taacacttgt tattgccttt ttttttttat 59400 tgtagccatc tagtaggtat caattgtcag gttaccacct tgccatttaa tcttttcttt 59460 ctgtagaatt ggccttgaat ccacctcttg aagatcagat tatgactact tagcaaatat 59520 gaataatacc tagtgacaag ttttgtccaa ttcagtcttt agaacttgta aagtttaatt 59580 ctttgctaac taacttagta taacagagtg gattgagtta gaaattttta ttaacttagg 59640 actcaagtgg atggtcatgg tcattgtagt tctttatttt tgtctctttg catctttata 59700 ttacacaaca gccttcattt ttgtgtttcc attttgttta aatttttaaa aatttaagtt 59760 gtttgaagga ctcgagtttc tggaaataat tgctttctcc atgtttatgt atcattttcc 59820 ctaccatgat taattttaat tagcttttag ggatttgttt gtttgtttgt ttgtttcatt 59880 gagacagtgt ctcactctgt cacccaggct ggagtgcggt ggcgctatct cagctcactg 59940 caacctccgc ctcccaggct caagcaatcc tcccatctgt ctcctgagta tctgggacta 60000 caggagcccg ccaccacgcc tgctaatttt tgtatttttt gtagagacgg agcttcacca 60060 tgttgoccag gctggtctca aactcctgag ctcaagcaat ccaccctgcc tcagcctccc 60120 aaagtgccag gattacaggt gtaagccacc gtgcctggcc agtattttat ttttaaataa 60180 atattcttta tagaaaatgt ggaaagtatt gaaaaataca aagagaagga ataaaattct 60240 cacactceag atagtctttg ttgatgtaca gtgrtacgtac tttcattttt ttacctatgc 60300 ttttaaaaaa taccttatat gaatatatac acacattcac aacaaccagg ttttgaatac 60360 ctagaaggag ttagaaccca acaagatgac ccctgtgtca tagaacatgg tttctgtttg 60420 ctgaaactga caccctagat taactatagg ataggacttt aatgaaggat ttattgattg 60480 ttccacctac agatgaatct atagagcttt acatacagaa tcttattctt ctctttctct 60540 ctctetcccc ccttcctccc tctcoaococ ctctttactg tctactctgg tttcctagga 60600 actctagcca agaaccacgg cctacactct ccaacacaat ccagaggcca caactaggtc 60660 ccacagctaa tttacccctg gagatgggct caggacagct ggcacccagg taaaaaaggg 60720 tgaaataatc atctgttgag cagtcaccca gggggtggtc atttgcaatc ccatatattt 60780 tttgttcggt tggttaattt tttttttttt tttttgagaa ggagttttgc tctcattgct 60840 caggctggat ggaatacaat ggcacgatct. aggctcactg tgacctctgt ctcctgggtt 60900 caagtgattc acctgcctca gcctcccaaa tagctgggat tacaggtgcc tgccaccacc 60960 cccggctaat tttttgtatt tttagtagag acggggtttt gccatgttgg ccaggctggt 61020 gtcgaactcc tgacctcagg tgatccacct gcttcggcct cccaaagtgt tgggattaca 61080 ggcatgagcc accatgcccg gcctgtttaa tttgttttaa ggttctttct ccagattctt 61140 tttaaaaaaa aatttttttt tctatttgtc ttgtcaactg gcctttgaca tataggcagc 61200 agcaacagca aacagaattg gacatggtac caggaagaga tggactggcc agctacaatc 61260 attcccaggt gagttgtgtc ctcttcgttg aagagggtag ggagtattta cttaggaagt 61320 gttctccggt actagttaga atgtacatat gttgtatatg aattttaggg ttattgaatt 61380 gtcatgttaa atctttaatg gttattttta tcattgtatt ccacaggtgg ttcagcctgt 61440 gacaaccaca ggaccagaac acagcaagcc ccttgagaag tcagatggtt tatttgccca 61500 ggatagagat ccaagatttt cagaaatcta tcacaacatc aatgcgggta tgtttctttc 61560 tcattatcct tttaaattct catttagatc acttactgat gggcatgcca ctgcccagtc 61620 agtaatcttc cagtgttttt ccacttaatc ataataccac ctgagtaaat aggaacttgc 61680 tgaactaata tactacagcc ccttgactgg cccttcccca actccttttg gtccacagat 61740 cagagtaaag gcatctcotc oagcactgtc cctgccaccc aacagctatt ctcccagggc 61800 aacacattcc ctcctacccc ccggccggca gagaatttca ggtgagcccc gtatatatgt 61860 gctgctttac agggccctga gggattcagc tgctgaatcc aaattttatt cttcccttgc 61920 tttctctggt tacttcagaa aaagcagtga agcttgtagg gcctagcgtg aggcaaacaa 61980 gctgcttttc ttcctcctat ttctttgcac ctgtcctatt gccatgttct aggctccatc 62040 tctgtgtgtc ctggtcagtg tgtgactgtc agtctttctt gtcttttcca aattgttatc 62100 aaattttcct taacctgcag gaagtcaagg ggatctaggg atagcactag attgtccttt 62160 gattcctagc ttctgtgata aatctatcct tttaatcttt tacctoattt attoactcct 62220 aggaatagtg gcctagcccc tcctgtaacc attgtccagc catcagcttc tgcaggacag 62280 atgttggccc agatttcccg ccactccaac cccacccaag gagcaacccc aacttggacc 62340 cctactaccc gctcaggctt ttctgcccag gtaaaactta tcatctgtgt gttccctgtg 62400 tattattttt tgtttgtttg ggcttttttc cgtatgtaaa atcagtgttt tctattttaa 62460 ataccttctc cccaacccct gttctccggt ttccaatttc catctttgtt gagagtagct 62520 aattaaaaat cacagataat aaaaaaaaat ctcagtagag tctgtggttt tcaccttaaa 62580 tcagaattgc tcacttggaa cgttttgagc acgtctgatt ttcagatttg ttttggagta 62640 aattctaaga tgtttcctct ttgtttagga ctccataagg caggagcaaa ggagaaaatt 62700 aatgactaac ttacagtgat gtctgtttac aaaaaagttg aaaaattctt tttttttttt 62760 tttttgagac agagtcttgc tctgtcgccc aggctagagt gcagtggtgc gatcttggct 62820 cactgcaagc tctgcctccc gggttcacgc cattctcctg cctcagcctt ccaagtagct 62880 gggaettgta caggcgcccg ccactgcgcc taattttttt tttttgtatt tttagtagag 62940 atggggtttc accatgttag ccaggatggt ctcaacctcc tgaccttgtg atccgcccac 63000 ctcagcctcc caaagtgctg ggattacagg cgtgagccac cgcgcctggc tgaaaaattc 63060 tttttttttt tttttcttga gacagactgt cactttgttg cccaggctct ggagtgcagt 63120 ggcgcgatct cggctcactg caagctccgc ttcctgggtt catgccattc tcctgcctca 63180 gcctcccgag tagctgggac tacagggtgc tcgccaccac gcctggctaa ttttttgtat 63240 ttttagtaga gacggcattt caccgtgtta gccaagatgg tcttgatctc ttgacctcgt 63300 gatccgccct cctcggcctc ccaaagtgct gggattacag gcatgagcca ccgcatccag 63360 ccgaaaaatt cttttataat attcatatat ataatataac gcacaataaa tacactgtct 63420 aaagaaagat tctttaatat tactatatat ttatgttata caagtaatag ttttaaaaag 63480 tcaaaaccaa aagcaggttc cagaatgtta tatgcaatac gatctcaatt gtgtacaaaa 63540 tgcatgagaa aatagaaact ggaagaaatt atccaaacat gttaaccatg gaattatgaa 63600 tgattcttat tttotttata ttttccttca ctttctgaat attctataat gcatatacag 63660 aactctcatg agaaaatagt ttttataaaa aatacatcat taggaacaaa tgaatgcaga 63720 acagacagaa taatggtgca gagtagtttt tctctgcata tggtactttt tttgttgttt 63780 gtttttttga gacagagtct cgctgttgcc caggctagag tgcagtggcg cgatcttggc 63840 tcactgcaac ctctgtctcc cgggttcaag tgattctoct gcctcagcct cctgggttgc 63900 tgggattaca ggoacgtgcc accatgccca gctaattttt gtatttttag tagagacggg 63960 gatttcacca tgttggcccg gctggtctgg aactcctcac ctcaggtggt ctgcctgcct 64020 tggcctccca aagtgctggg attataggca tgagccatga gccaccccgc ctggcctgca 64080 tataatactt tactgttatg aatgcctcta gttttatata acttcacagt ttataagatg 64140 ctttcattta attcttacaa tttttattaa tcccatagtt cattgctttt ttgtaatttt 64200 atctcagctg cctaaaaaat agtgtcaaga gagattgaga gttaattgga agaaatatac 64260 aataggaaat aagtgatgag cttggttcag aaggatgcag tgattgacag tgttgactct 64320 cataggcatg gtatgtgcaa tgatgttaat gctgtatttg ttctatatcc cctctccatc 64380 tctctttagc aggtggctac ccaggctact gctaagactc gtacttccca gtttggtgtg 64440 ggcagctttc agactccatc ctcottcago tccatgtccc tccctggtgc cccaactgca 64500 togcctgçrtg ctgctgccta ccctagtctc accaatcgtg gatctaactt tggtgagtcc 64560 agaccataag gagagtaaca ggaaaatcgc accactaaag agaaaggatt tggtagttaa 64620 agttgtttgc ctgtgttgtg ggtacactga cctgattgta gggaaatgca aggtgacaat 64680 ctatttagaa tttaaaacct accagctggg tgcggtggct cacgcctgta ataccagcac 64740 tttgggaggc tgaggcaggc ggatcacttg aggttgggag ttcaacccca gcctgaccaa 64800 catggagaaa ccctgtctct accgggtgtg gtaccgcatg cctgtaattc cagctactcg 64860 ggcggctgag gcaggagaat cgcttgaacc caggaggcag aggttgcggt gagctgagat 64920 cgcgcctttg cactccagcc tgggcaacaa gagtgaaact ccgtctcaaa aaaataaaaa 64980 ataaaaaaaa aaaactaccc acatgaaaaa tactttagca catataacaa aaatcatgtg 65040 aatttttata catttaatag tatgcacatt taacctaaat gagtaaagaa ctctatggaa 65100 aggctgcctg gagaagaaga attaatttag ggctgagttt tgagatagaa aaggcattga 65160 ttggcagaga gaaggacaga gttatcctag gtaaaattaa tggcttacct atagttgttt 65220 acttgtggca ttagtacaoa atggaattgt gtagattgga gttgtttatt cttocttgct 65280 gtatttctag ctcctgagac tggacagact gcaggacaat tccagacacg gacagcagag 65340 ggtgtgggtg tctggccaca gtggcagggc cagcagcctc atcatcgttc aagttctagt 65400 gagcaacatg ttcaacaacc gccagcacag caacctggcc agcctgaggt cttccaggta 65460 agagagtgaa aagactttca aaaattagaa gctgggagag aaagggtcca ggaggaggag 65520 agacagtgaa ggaagcatgc ctggattgag gtgtttggtt gggggtatat gtgagaagac 65580 agagagggat aaatgtaggg atcactgtca gttattgaaa agattgcaga agctagatgc 65640 agtggtgctt gtgtatatga tgtcagcccc ttagaaggct gaagcagggg atcacttgag 65700 gccatgagtt caaagccagg ctgagcaact agcctgatcc tgtccctgtc aaacaaacaa 65760 aaaaggagta tgaattgagt gtgatacata ccatttaacc agaacagaca aatttagcac 65820 cataggaaga tgccaaagaa agttacttta gctcattcaa atagctccat atacccaagt 65880 cacagtagct ttgggtttaa aagagacaga atgattaaaa ataaaaagta gtgctcgctt 65940 cagcagcata tatactaaaa ttggaatgaa tatagagaag attagcatgg cccctgcgta 66000 aggatgacac acaaattcat gaagtgttcc atttaaaaaa ttataaaaag taaatgaaat 66060 agaacataat gattatagcc ataatggtct atttacacaa gtcctgaggg actgcaagag 66120 tgaatggagt aatcttaggc aggacaaagg aagagctggt ttaaagcaaa gattgaaaga 66180 aagcaaaaca ggtcttggtg gaaaacaaat aggataagag actccatata tgtctatagg 66240 gggttatatg aaatacagca agcagatttt tctccctttg aaaatattga gaactaggaa 66300 aaggaaaaag gtggaactgt aggaggaaga cagaagggat taggaaaaaa ggctgcgatc 66360 taaaggagtc aaagttgttg gaagtaagga aggctaagag ctcagcacag caaagactcg 66420 gggtcaggga tggtagtgca ggggaatggt ggagtagaac ttggtaagtg taagagatca 66480 aggtgtgtga cccaaactta atctttttct tttatcagga gatgctgtcc atgctgggag 66540 atcagagcaa cagctacaac aatgaagaat tccctgatct aactatgttt cccccctttt 66600 cagaatagaa ctattggggt gaggataagg ggtgggggag aaaaaatcac tgtttgtttt 66660 taaaaagcaa atctttctgt aaacagaata aaagttcctc tcccttccct tccctcaccc 66720 ctgacatgta ccccctttcc cttctggctg ttcccctgct ctgttgcctc tctaaggtaa 66780 catttataga agaaatggaa tgaatctcca aggcttttag gactgtctga aaatttgagg 66840 ctgggtgaag ttaaaacacc tttccttatg tctcctgacc tgaaattgta tagtgttgat 66900 ttgtgctgag atcaagaggc aggttagaag aacctgacat ccactgtttg ccttggatag 66960 tatggcttgt ttttggaaag aaattcfcgaa gagagtggag gagaggagaa atgtcctcat 67020 atttgaggac catgaaacat tgtaggtata tatggggctt tagcaagttt gagcataggc 67080 tctttttgct gcctgtgagc agtccctctg gaaagaaaca tgtgagtaag tgagagagag 67140 tgtgtgtgta tgtgtgtgtg tgtgtgtgtg cgcacacatg cttctgtatt tcactctttc 67200 tcccfcattag ggagtfcafcgc aaaatttgtc ccegatttta cctttgtctt tctgtgtact 67260 tttcaaagag tcctaaggag ttaaatcttc caggtatttt ccacttagta ttgcagccaa 67320 agaatattta aataaacgtc tttgctgcgc ttgcatccat gcccagccaa tatacaactg 67380 taaagcaaat atagaaagtc ggctgttgat acgattgtct gttatcgaac acattcagtg 67440 ataaagctgg gttactgctg cttttggtgc tctcacctta tctggaagat ctgcaaacat 67500 tacctaaata ggctggcaag ataaacactt tctggaaccc gagacttggc cataaagata 67560 atgctgcatt tttctgtcag aatcacatat gatgtgtgtt ctgtagaggt tatttctgca 67620 tggaaactca acttcttgga ttagccgtcc cagtgaaaat cctcattgtt ggagtgtaaa 67680 ccaaatacga agccctcttg caaagtagcc tctttcatcc catactcaaa atacccagtt 67740 tagcaagcaa ctgagattta agtctctctg gccctaagag gtttttcctc tttgctccct 67800 ccaatcttga gattgggttt tgctttagag tgcaagtatc ataattccgt atgatagatg 67860 gggccctgga cacccatctc aacagggtca cttggtaatt aacaataata gccatataaa 67920 tgcggataca ggttactacc ctcacccttt accttcctca ggtaacagtc gtagatacca 67980 gctttttttt tttttttttt aaattggctt tggccagtag ctaaagtgca agactgaatt 68040 aatgagaaga tatattaaat gtagtcatag gggactgagg agcaagggtg gccttgaaga 68100 ggccaaagga atgtccattt gctgagtttc ccttccttat gtctccagtc tggtgccagg 68160 tagtggagta aaaaaggaga cagtttattt ttttattcta tgtgcacact tacagtatac 68220 atatatattt atatcacaat ttacgaaacc aaaaagttga gtttccaatg gaacccttgt 68280 tttttaataa tcgacttttt aaatgtgato aggactataa tattgtacag ttattatagg 68340 gcttttgggg aaggggagga tagcgagaag atgctctggg ggttttgttt ttgcttttcc 68400 ttcagggttt tatttttgac tgttttgttt tcttgttggc catttctçrta ttgctggcat 68460 ctgtgctaag ctttacagtg gcaaaaataa tgacatgtag caaagatttt caaacaaaat 68520 attttttcct tttgtaaaat ttcttgtgtt gtgtgatctt gattgcggct ttatcattcc 68580 tttccagttc ataaacaaca ggcacccaca accagaggaa tctatagttt aagctccaga 68640 catacaaaca taaggcacat tgtgtcttta atttcaggaa tcagaaatca tagggttctg 68700 atcacattgc acgcctcccc cctcacttgt cctcctgatc ctgacacatt ctgagtaaca 68760 tcagcaggaa tgct 68774

<210> 50 <211> 2446 <212> ADN <213> Homo sapiens <400> 50 ggccgggcgg gcatgggcct tcocggcccg gagctgggag tcgaaggggc gggaggcgtg 60 atggtgaact cgcaagaagt ttgagggacg cgcgggccoo gcgcccactc cccctccacc 120 ggacacggct ggggccggcg atgcotgaga gggggtcgga ggacgcagtg aacatatatg 180 catgtacagt gtggatcctc atctgagagg agggagatga aaacacaccc acctcacagg 240 ctgttgtgag gactaagggt gcggcagtgc ctggtacatg ggagccagcg ccggcagcca 300 ccatggcgtc acgcataggg ttgcgcatgc agctcatgcg ggagcaggcg cagcaggagg 360 agcagcggga gcgcatgcag caacaggctg tcatgcatta catgcagcag cagcagcagc 420 agcaacagca gcagctcgga gggccgccca ccccggccat caataccccc gtccacttcc 480 agtcgccacc acctgtgcct ggggaggtgt tgaaggtgca gtcctacctg gagaatccca 540 catcctacca tctgcagcag tcgcagcatc agaaggtgcg ggagbacctg tccgagacct 600 atgggaacaa gtttgctgcc cacatcagcc cagcccaggg ctctccgaaa cccccaccag 660 ccgcctcccc aggggtgcga gctggacacg tgctgtcctc ctccgctggc aacagtgcfcc 720 ccaatagccc catggccatg ctgcacattg gctccaaccc tgagagggag ttggatgatg 780 tcattgacaa cattatgcgt ctggacgatg tccttggcta catcaatcct gaaatgcaga 840 tgcccaacac gctacccctg tccagcagcc acctgaatgt gtacagcagc gacccccagg 900 tcacagcctc cctggtgggc gtcaccagca gctcctgccc tgcggacctg acccagaagc 960 gagagctcac agatgctgag agcagggccc tggccaagga gcggcagaag aaagacaatc 1020 acaacttaat tgaaaggaga cgaaggttca acatcaatga ccgcatcaag gagttgggaa 1080 tgctgatccc caaggccaat gacctggacg tgcgctggaa caagggcacc atcctcaagg 1140 cctctgtgga ttacatccgg aggatgcaga aggacctgca aaagtccagg gagctggaga 1200 accactctcg ccgcctggag atgaccaaca agcagctctg gctccgtatc caggagctgg 1260 agatgcaggc tcgagtgcac ggcctcccta ccacctcccc gtccggcatg aacatggctg 1320 agctggccca gcaggtggtg aagcaggagc tgcctagcga agagggccca ggggaggccc 1380 tgatgctggg ggctgaggtc cctgaccctg agccactgcc agctctgccc ccgcaagccc 1440 cgctgcccct gcccacccag ccaccatccc cattccatca cctggacttc agccacagcc 1500 tgagctttgg gggcagggag gacgagggtc ccccgggcta ccccgaaccc ctggcgccgg 1560 ggcatggctc cccattcccc agcctgtcca agaaggatct ggacctcatg ctcctggacg 1620 actcactgct accgctggcc tctgatccac ttctgtccac catgtccccc gaggcctcca 1680 aggccagcag ccgccggagc agcttcagca tggaggaggg cgatgtgctg tgaccctggc 1740 tgcccctgtg ccagggaaca ggggccggcc tgggggctgg gagggccagg ggcacctccc 1800 tcccaccctt caggctgcac tgtgtgtgaa gtagccacct gccctgcctc cctcctcccc 1860 gttggcccct gtttggactt agtgcctgtc tggcagcctg tggggtcagg agaagcaccc 1920 ccagggcagc cctcttgact ggcgcagtgg gaagaggcct tcagcccctc tcccggagat 1980 ggaatcgcgg ggcagggagg ggcagggtgt tctagaggtg agaagagggc ctggtggaga 2040 ttccctgtct tctgagcccg agcccctcat taccagtgaa ggacatgctt gaggggttcg 2100 ggaagctcct catctgaggc aactggtcct gggggtgctc aggcctgcct ttttgggact 2160 cagatggcag gaggtccacc ccgcagcctg gtcctcggct ctcccacagg tgggcacccc 2220 ccactttggt gctaatagct ctccaocagg tggtgtgagc gcgggggctg ccagaagcgg 2280 gaggggtcac tgccggaaga gcagctgccc tccgacccct cactttgtgc ctttagtaaa 2340 cactgtgctt tgtaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 2400 aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaa 2446

<210> 51 <211> 681 <212> ADN <213> Homo sapiens <400> 51 atggattggg gcacgctgca gacgatcctg gggggtgtga acaaacactc caccagcatt 60 ggaaagatct ggctcaccgt cctcttcatt tttcgcatta tgatcctcgt tgtggctgca 120 aaggaggtgt ggggagatga gcaggccgac tttgtctgca acaccctgca gccaggctgc 180 aagaacgtgt gctacgatca ctacttcccc atctcccaca tccggctatg ggccctgcag 240 ctgatcttcg tgtccacgcc agcgctccta gtggccatgc acgtggccta ccggagacat 300 gagaagaaga ggaagttcat caagggggag ataaatagtg aatttaagga catcgaggag 360 atcaaaaccc agaaggtccg catcgaaggc tccctgtggt ggacctacac aagcagcatc 420 ttcttccggg tcatcttcga agccgccttc atgtacgtct tctatgtcat gtacgacggc 480 ttctccatgc agcggctggt gaagtgcaac gcctggcott gtcccaacac tgtggactgc 540 tttgtgtccc ggcccacgga gaagactgtc ttcacagtgt tcatgattgo agtgtctgga 600 atttgcatcc tgctgaatgt cactgaattg tgttatttgc taattagata ttgttctggg 660 aagtcaaaaa agccagttta a 681 <210> 52 <211> 30 <212> ADN <213> Artificial <22 0> <223> uma sequência iniciadora sintetizada artificialmente <400> 52 gagctagcca ccatggtgag caagggcgag 30 <210> 53 <211> 21 <212> ADN <213> Artificial <22 0> <223> uma sequência iniciadora sintetizada artificialmente <400> 53 tcaccttgat gccgttcttc t 21 <210> 54 <211> 24 <212> ADN <213> Artificial <22 0> <223> uma sequência iniciadora sintetizada artificialmente <400> 54 taactgggtc gagcacagtg atgc 24 <210> 55 <211> 29 <212> ADN <213> Artificial <22 0> <223> uma sequência iniciadora sintetizada artificialmente <400> 55 tcagaattga tctggtcttc aagacctbg 29 <210> 56 <211> 27 <212> ADN <213> Artificial <22 0> <223> uma sequência iniciadora sintetizada artificialmente <400> 56 atgtatgcta tacgaagtta ttagggc 27 <210> 57 <211> 24 <212> ADN <213> Artificial <22 0> <223> uma sequência iniciadora sintetizada artificialmente <4Ο0> 57 ccctcgtgga tggttgccag cage 24 <210> 58 <211> 27 <212> ADN <213> Artificial <22 0> <223> uma sequência iniciadora sintetizada artificialmente <400> 58 cttactttgc actgaacaca cacatcc 27

Claims

REIVINDICAÇÕES

1. Método para introduzir um polinucleótido arbitrário especificamente numa célula trofectodérmica não humana, o qual compreende os passos de: (a) remover a zona pelúcida de um blastocisto não humano; e (b) introduzir um polinucleótido arbitrário nas células trofectodérmicas do blastocisto obtido no passo (a).
2. Método de produção de um blastocisto não humano compreendendo uma célula trofectodérmica especificamente introduzida com um polinucleótido arbitrário, o qual compreende os passos de: (a) remover a zona pelúcida de um blastocisto não humano; e (b) introduzir um polinucleótido arbitrário nas células trofectodérmicas do blastocisto obtido no passo (a).
3. Método da reivindicação 1 ou 2, em que o polinucleótido arbitrário é um polinucleótido que codifica uma proteína essencial para o desenvolvimento fetal ou um polinucleótido que regula a expressão da proteína.
4. Método da reivindicação 3, em que o polinucleótido que codifica uma proteína essencial para o desenvolvimento fetal é pelo menos um polinucleótido selecionado do grupo consistindo em: Dlx3, Fgfr2, Fral, Fzd5, Gabl, Gcml, hipomorfo Grb2, Gja7, Hgf, Hsp84-1, Itgav, Junb, Lifr, ERK1, ERK2, ERK5, MEK1, MEKk3, ρ38α, ρ38β, Met, Pdgfra, Pdgfb, Pparg, Rxra, Rxrb, Sosl, Vhlh, Wnt2, Ets2, Mash2, Egfr, Hsfl, Bmp5, Bmp7, Dnmtl, Itga4, Lhxl, Mrj, Tcf, Lef, Cdx2, Eomes, Fgf4, Esrrb, Handl, Mdfi, Esxl, Arnt, Tcfeb e Gjb2 .
5. Método de qualquer uma das reivindicações 1 a 4, em que o blastocisto é derivado de um animal não humano tendo uma anormalidade numa proteína essencial para o desenvolvimento fetal ou na regulação da expressão da proteína.
6. Método de qualquer uma das reivindicações 1 a 5, em que a zona pelúcida é removida por tratamento ácido, tratamento enzimático ou tratamento físico.
7. Método da reivindicação 6, em que o tratamento ácido é um tratamento com solução de Tyrode ácida.
8. Método da reivindicação 6, em que o tratamento enzimático é um tratamento com pronase.
9. Método de qualquer uma das reivindicações 1 a 8, em que o polinucleótido é introduzido infetando um blastocisto com um vetor virai portador de um polinucleótido desejado.
10. Método de qualquer uma das reivindicações 1 a 8, em que o polinucleótido é introduzido utilizando um reagente de transfeção de ácido nucleico.