MXPA00007165A

MXPA00007165A - Meth1 and meth2 polynucleotides and polypeptides.

Info

Publication number: MXPA00007165A
Application number: MXPA00007165A
Authority: MX
Inventors: A Hastings Gregg
Original assignee: Beth Israel Hospital
Priority date: 1998-01-23
Filing date: 1999-01-22
Publication date: 2002-06-21
Also published as: CA2319109A1; CN1292796A; JP2002501077A; KR20010086224A; WO1999037660A9; AU766787B2; NZ505855A; EP1049708A1; WO1999037660A1; EP1049708A4; AU2464199A

Abstract

The present invention relates to novel anti-angiogenic proteins, related to thrombospondin. More specifically, isolated nucleic acid molecules are provided encoding human METH1 and METH2. METH1 and METH2 polypeptides are also provided, as are vectors, host cells and recombinant methods for producing the same. Also provided are diagnostic methods for the prognosis of cancer and therapeutic methods for treating individuals in need of an increased amount of METH1 or METH2.

Description

POLINUCLEOTIDES AND POL I PEPT TOS OF METHl AND METH2 FIELD OF THE INVENTION The present invention relates to novel anti-angiogenic proteins, related to the t ombospondi na. More specifically, isolated nucleic acid molecules encoding human METH1 and METH2 (ME, for metalloprotease, and TH, for tr ombo sp ond ina) are provided, the METH1 and METH2 polypeptides are also provided, as are vectors, host cells and recombinant methods to produce them. Diagnostic methods for cancer prognosis and therapeutic methods are also provided to treat individuals in need of an increased amount of METH1 or METH2.

BACKGROUND OF THE INVENTION Angiogenesis, the formation of new blood vessels from the vasculature pr e-ex i s t in t, is a process that Ref. : 121519 - - It is very well regulated in normal adults. Under physiological circumstances, the growth of new capillaries is strictly controlled by an interrelationship of growth-regulating proteins that act either to stimulate or to inhibit the growth of blood vessels. Normally, the balance between these forces is given in favor of inhibition and as a consequence the growth of blood vessels is restricted. However, under certain pathological circumstances, local inhibitory controls are capable of restricting the increased activity of angiogenic inducers. Angiogenesis is a key stage in cancer metastasis (Folkman, Nature Med. 1: 21-31 (1995)) and in the abnormal healing of wounds, inflammation, rheumatoid arthritis, psoriasis, and diabetic retinopathy, is integral to the pathology (Folkman, et al., Science 235: 4 ^ 2-447 (1987)), generating the hope that these pathological entities could be regulated by the pharmacological and / or genetic suppression of the growth - of the blood vessels (Iruela-Arispe et al., Thromb. Haem 78: 612-611 1997)).

The rhombbospondi na-1 (TSP-1) is an adhesive glycoprotein an t i - ang i ogen i ca 450 kDa, released from platelets activated and secreted by growing cells (reviewed in Adams, Int. J. Biochem. Cell.

Biol. 29: 861-865 (1997)). TSP-1 is a homotrimer, with each subunit comprised of a polypeptide of 1152 amino acid residues, modified post-translationally by N-linked glycosylation and beta-hydroxylation of asparagine residues.

The TSP-1 protein and the AR? M levels are regulated by a variety of factors. The levels of the TSP-1 protein are down-regulated by alpha IL-1 and alpha T? F. The RA? M of TSP-1 and protein levels are up-regulated by the growth factors of the polypeptide including PDGF, TGF-beta, and bFGF (Bornstein, Faseb J. 6: 3290-3299 (1992)) and they are also regulated by the expression level of the p53 tumor suppressor gene product (Dameron et al., S ci in ce 2 65: 1582-1584 (1994)). At least four of the other members of the rhombospond family have been identified: TSP-2, TSP-3, TSP-4, and TSP- (also called COMP). There is a need in the art to identify other molecules involved in the regulation of angiogenesis.

BRIEF DESCRIPTION OF THE INVENTION The present invention provides nucleic acid molecules, isolated, comprising a polynucleotide that encodes the METH1 polypeptide having the amino acid sequence shown in SEQ. ID NO: 2 or the amino acid sequence encoded by the cDNA clone deposited in the bacterial host as the Deposit Number of ATCC 209581 of January 15, 1998.

The present invention also provides isolated nucleic acid molecules encoding the METH2 polypeptide having the amino acid sequence shown in SEC: ID NO or the amino acid sequence encoded by the cDNA clone deposited in a bacterial host such as Deposit Number ATCC 209582 of January 15, 1998.

The present invention also relates to recombinant vectors, including the isolated nucleic acid molecules of the present invention, and to host cells which contain the recombinant vectors, as well as to the methods of preparing such vectors and host cells and to use them for the production of METH1 or METH2 polypeptides or peptides by recombinant techniques.

The invention further provides a METH1 or METH2 polypeptide having an amino acid sequence encoded by a polynucleotide described herein.

The invention also provides a useful diagnostic method during the diagnosis or prognosis of cancer.

A further aspect of the invention relates to a method for treating an individual in need of an increased level of METH1 or METH2 activity in the body which comprises administering to such an individual a composition comprising a therapeutically effective amount of an isolated METH1 polypeptide. or METH2 of the invention or an agonist thereof.

BRIEF DESCRIPTION OF THE FIGURES Figure 1 shows the nucleotide (SEQ ID NO: 1) and the deduced amino acid sequences (SEQ ID NO: 2) of METHl. The protein has a predicted leader sequence of approximately 28 amino acid residues (underlined).

Figure 2 shows the nucleotide (SEQ ID NO: 3) and the deduced amino acid sequences (SEQ ID NO: 4) of METH2. The protein has a predicted leader sequence of approximately 23 amino acid residues (underlined).

Figure 3 shows a comparison of the amino acid sequence of METHl (SEQ ID NO: 2) and METH2 (SEQ ID NO: 4) with that of its closest homologue, a bovine metalloprotease (pNPl) (SEQ ID.

NO: 5). Identical amino acids are enclosed in frames The functional DNAs predicted by structural and sequence homology are labeled, which include the signal peptides (single lines), the potential cleavage sites for mammalian subtilisin (double underlined), the site Link to zinc (dashed lines) in the metalloprotease domain, and the putative disintegrin circuits (arrows).

Figure 4 shows the primary structure of METH1, and METH2 and pNP1 including a prodomain, a catalytic metalloprotease domain, a cysteine-rich disintegrin domain, a TSP-like domain, a spacer region, and a different number of similar domains.

TSP, three for METHl, two for METH2, and four for pNPl.

Figure 5 shows a comparison of the TSP-like domain of METH1 (SEQ ID NO: 2) and METH2 (SEQ ID NO: 4) with those of TSP1 (SEQ ID Nos: 6, 7 and 8) and TSP2 (SEQ ID Nos: 9, 10 and 11), the cysteines are numbered from 1 to 6, the tryptophan are marked by asterisks.

Figure 6 shows the peptides and recombinant proteins derived from the TSP-like domain of the VEGF-induced angiogenesis of the METH1 and METH2 blocks. Angiogenesis was induced in the CAMs of 12-14-day-old embryos using a nylon mesh containing VEGF fused in matrigel in the presence or absence of the peptides or recombinant proteins before. The capillary density was evaluated as described in Example 4. The positive and negative control included VEGF alone and - -alone vehicle, respectively. (A) The quantification of the angiogenic response induced by VEGF in the presence of the recombinant proteins. TSP1, the purified purified TSP1, GST, GST, GST-TSP1, GST-METH1 GST-METH2 purified platelets are described in Example 4. (B) The quantification of the angiogenic response induced by VEGF in the presence or absence of the peptides; P-TSP1, P-METH1, and P-METH2 (peptide derived from the Type I repeats of TSP, METH1 and METH2, respectively); SCI and SC2 are mixed peptides used as controls, (C) Dose response of angiogenesis induced by VEGF in the presence of GST-METH1. (D) Response to the dose of angiogenesis induced by VEGF - in the presence of GST-METH2. The angiogenic index was expressed considering the VEG vascular response F-ma t ri ge 1 as 100% and subtracting the background levels (matrigel alone). The tests were repeated at least two times. Each treatment was done in triplicate. The values represent the mean, the bars - they indicate the standard deviations p < 0.001 Figure 7 shows the effect of recombinant proteins METH1 and METH2 on cell proliferation stimulated by bFGF. Cells were grown in 24-well plates in a medium containing bFGF and the recombinant protein to be tested (3 μg / ml, unless indicated in the .graph). The. controls included the vehicle or recombinant GST protein alone (A), HDEC, human dermal endothelial cells; (B), the HMEC, the human mammary epithelial cells; (C), HDF, human dermal fibroblasts; (D), the SMC, smooth muscle cells, (E) Dose response of GST-METH1 and GST-METH2 in the proliferation of HDEC. The experiments were repeated at least twice. Each treatment was done in triplicate. The values represent the measure, the bars indicate the standard deviations. * p < 0.01.

Figure 8 shows a schematic representation of pHE4-5 (SEQ ID NO: 12) and the coding sequence of METH1 cDNA or subcloned METH2. The locations of the kanamycin resistance marker gene, the METH1 or METH2 coding sequence, the oriC sequence, and the laclq coding sequence are indicated.

Figure 9 shows the nucleotide sequence of the regulatory elements of the Phe promoter (SEQ ID NO: 13). The two sequences of the operator l a c, the sequence Sh i -n e - De 1 ga rn (S / D), and the terminal restriction sites J i id id and N d e l (in italics) are indicated.

Figure 10 shows an analysis of the amino acid sequence of METH1. The alpha, beta, spin and turn or spiral regions: the hydrophilicity and hydrophobicity regions; anf ipáticas; flexible; the antigenic index and the surface probability are shown, and all were generated using the default settings. In the graph of the "Antigenic or Jameson-Wolf index", the positive peaks indicate the locations - of the highly antigenic regions of the METH1 or METH2 proteins, that is, the regions of which the peptides carrying the epitopes of the invention can be obtained. The domains defined by these graphs are contemplated by the present invention. The tabular representation of the data summarized graphically in Figure 10 can be found in Table 1.

Figure 11 shows an analysis of the amino acid sequence METH2. The alpha, beta, back and spin regions; the regions of hydrophilicity and hydrophobicity; unfriendly flexible; the antigenic index and the surface probability are shown, and all were generated using the default settings. In the graph of the "Antigenic or Jameson-olf index", the positive peaks indicate the locations of the highly antigenic regions of the METH1 or METH2 proteins, that is, the regions from which the peptides carrying the epitopes of the proteins can be obtained. the invention. The domains defined by these graphs are contemplated by the present invention. The tabular presentation of the data summarized graphically in Figure 11 can be found in Table 2.

In table 1 and 2.

Alpha = alpha Beta = beta Turn = spin Coil = spin or spiral Hydro = hydro Flexi = flexible Antig = old Surta = surface o! 0 twenty C5 r-4 or or r 5 e or rvi r os or • rs o o or rvi C5 r-4 3 r os OR OR or or f-1 or r-i or fvJ or or r ovi OR or f? as H O or is OR or O rs or or O.}. or rs • • - - 4 Í - - or rvi or r o-j í - - O C-l or O cs Red 08 -. 08 - as rs rs or I heard rs or or p OR gold OR or rs or rs or rs r os or rs DETAILED DESCRIPTION OF THE INVENTION The present inventors have identified two new proteins, METH1 and METH2 (also called VEGA-1 and VEGA-2, respectively, for the vascular endothelial growth antagonist), by selecting cDNA libraries with the cDNA encoding the anti-viral domain. Angiogenic of TSP-1, which contain the anti-angiogenic domain of TSP-1, a metalloproteinase domain, and a domain similar to disintegrin. The present inventors have shown that both METH1 and METH2 have anti-angiogenic activity.

Thus, the present invention provides isolated nucleic acid molecules comprising a polynucleotide encoding a METH1 polypeptide having the amino acid sequence shown in SEQ. ID NO: 2, which was determined by sequencing a cloned cDNA. The METH1 protein of the present invention shares sequence homology with the -t rombospondin-1 and pNPl. The nucleotide sequence shown in SEQ. ID NO: 1 was obtained by sequencing a cDNA clone, which was deposited on January 15, 1998 in the American Type Culture Collection, 10801 University Boulevard, Manassas, Virginia 20110-2209, and was given the accession number 209581. The cDNA clone contained in ATCC Deposit No. 209581 contains a METH1 sequence, which encodes amino acids 1 through 950 of SEQ. ID NO: 2 The present invention also provides isolated nucleic acid molecules comprising a polynucleotide encoding a METH2 polypeptide having the amino acid sequence shown in SEQ. ID NO: 4, which was partially determined by sequencing a cloned cDNA. The METH2 protein of the present invention shares the sequence homology with the t ombospondi na-1 and pNPl. The nucleotide sequence shown in SEQ. ID NO: 3 was obtained partially through the sequencing of a cDNA clone, which was deposited on January 15, 1998 in the American Type Culture Collection, 10801 University Boulevard, Manassas, Virginia 20110-2209, and to which He gave access number 209582. The cDNA clone contained in ATCC Deposit No. 209582 contains a partial sequence of METH2, which encodes amino acids 112-890 of SEC. ID NO: 4 Mo l C u l a s of A c i d o Nu c l e i c o Some of the nucleotide sequences determined by the sequencing of a DNA molecule of the present were determined using an automated DNA sequencer (such as Model 373 from Applied Biosystems, Inc.), and all the amino acid sequences of the polypeptides encoded by the DNA molecules determined herein were predicted by translating a given DNA sequence as indicated above. Therefore, as is known in the art for any given DNA sequence - by its automated methodology, any nucleotide sequence determined here may contain some errors. The nucleotide sequences determined by automation are typically at least about 90% identical, more typically at least about 95% to at least about 99.9% identical to the actual nucleotide sequence of the DNA molecule 10 sequenced. The actual sequence may be more precisely determined by other methods that include methods of sequencing Manual DNAs well known in the art. As is also known in the art, a 15 single insertion or deletion in a given nucleotide sequence compared to the actual sequence will cause a deviation in the structure in the translation of the nucleotide sequence such as the sequence 20 predicted amino acid, encoded by a given nucleotide sequence that will be completely different from the amino acid sequence actually encoded by the sequenced DNA molecule, starting at the 25 point of such insertion or elimination.

Using the information provided herein, such a nucleotide sequence in SEQ. ID NO: 1 or SEC. ID NO: 3, a nucleic acid molecule of the present invention that encodes a METH1 or METH2 polypeptide can be obtained using standard selection and cloning procedures, such as those for the cloning of cDNA using mRNA as the starting material. Illustrative of the invention, the nucleic acid molecule described in SEQ. ID NO: 1 was discovered in a cDNA library derived from the human heart and the nucleic acid molecule described in SEC. ID NO: 3 was discovered in a cDNA library derived from a human lung. The determined nucleotide sequence of the METH1 cDNA of SEQ. ID NO: 1, contains an open reading frame that encodes a protein of approximately 950 amino acid residues, which includes a predicted leader sequence of approximately 28 amino acid residues. The present inventors have determined that the nucleotide sequence of the - -METH2 cDNA of SEQ. ID NO: 3 contains an open reading frame that encodes a protein of approximately 890 amino acid residues, which includes a predicted leader sequence of approximately 23 amino acid residues.

The present invention also provides the mature forms of the METH1 and METH2 proteins of the present invention. According to the signal hypothesis, the proteins secreted by mammalian cells have a secretory or signal leader sequence that is cleaved from the mature protein once the export of the growing protein chain has begun. from the endo 1 to smi co reticulum Most mammalian cells and even insect cells cleave the secreted proteins with the same specificity. However, in some cases, the cleavage of a secreted protein is not entirely uniform, which results in two or more mature species in the protein. Furthermore, it has been known for some time that the cleavage-specificity of a secreted protein is ultimately determined by the primary structure of the entire protein, that is, that it is inherent in the amino acid sequence of the polypeptide. Therefore, the present invention provides a nucleotide sequence encoding the mature METH1 polypeptide having the amino acid sequence encoded by the cDNA clone contained in the host identified as ATCC Repository No. 209581 and as shown in SEQ. . ID NO: 2. The present invention also provides a nucleotide sequence encoding the mature METH2 polypeptide having the amino acid sequence as shown in SEQ. ID NO: 4. The mature METH1 protein having the amino acid sequence encoded by the cDNA clone contained in the host identified as ATCC Deposit No. 209581 indicates the mature forms of the METH1 protein, produced by the expression in a mammalian cell (e.g., COS cells, as described below) of the complete open reading frame encoded by the human DNA sequence of the clone contained in the vector in the deposited host. As indicated below, mature METHL having the amino acid sequence encoded by the cDNA clone contained in ATCC Deposit No. 209581 may or may not differ from the predicted "mature" METH1 protein shown in SEQ. ID NO: 2 (amino acids from approximately 29 to approximately 50) depending on the accuracy of the predicted cleavage site based on computer analysis; and mature METH2 may or may not differ from the predicted "mature" METH2 protein shown in SEC. ID NO: 4 (amino acids from approximately 24 to approximately 890) depending on the accuracy of the predicted cleavage site based on computer analysis.

Methods for predicting whether a protein has a secretory leader as well as a cleavage site for that leader sequence are available. For example, you can use McGeoch's methods - -. { Virus Res. 3: 271-286 (1985)) and von Heinje (Nucleic Acids Res. 14: 4683-4690 (1986)). The accuracy to predict the cleavage sites of mammalian secretory proteins known for each of these methods is in the range of 75-80%. von Heinje, supra. However, the two methods do not always produce the same predicted cleavage points for a given protein.

In the present case, the predicted amino acid sequence of the complete METH1 and METH2 polypeptides of the present invention were analyzed by a computer program ("PSORT") (K. Nakai and M. Kanehisa, Genomics 14: 897-911 (1992)), which is an expert system for predicting the cellular localization of a protein based on the amino acid sequence. As part of this computational prediction of localization, the methods of McGeoch and von Heinje are incorporated. Analysis by the PSORT program predicted the cleavage site between amino acids 28 and 29 in the SEC. ID NO: 2 and amino acids 23 and 24 in _ -the SEC. ID NO: * ??? tio rio mar ts "* = s complete amino acid sequences were further analyzed by visual inspection, applying a simple form of the rule (-1, -3) of von Heinje von Heinje, up. for the METH1 protein it was predicted that it consists of the amino acid residues from about 1 to about 28 in SEQ ID NO: 2, whereas the mature METH1 protein was predicted to consist of residues from about 29 to about 950; and the leader sequence for the METH2 protein was predicted to consist of the de-amino acid residues from about 1 to about 23 in the SEC. ID NO: 4, whereas the mature protein METH2 was predicted to consist of residues from about 24 to about 890. A mature protein predicted METH1 alternatively consists of residues 30 through 950 in the SEC. ID NO: 2 As someone with ordinary skills - in the art you will appreciate, due to the possibilities of sequencing errors, as well as the variability of the cleavage sites for the leaders in the different known proteins, the predicted METH1 polypeptide encoded by the cDNA The deposited comprises approximately 950 amino acids, but may well be in the range of 910-990 amino acids, and the predicted leader sequence of this protein is approximately 28 amino acids, but may be in the range of about 18 to about 38 amino acids. Also, the predicted METH2 polypeptide comprises about 890 amino acids, but may be in the range of 850 to about 930 amino acids; and the predicted leader sequence of this protein is about 23 amino acids, but it can be in any range from about 13 to about 33 ami no acids.

As indicated, the nucleic acid molecules of the present invention can be in the RNA form, such as mRNA, or in-the DNA form, which includes, for example, cDNA and the genomic DNA obtained by cloning or produced Yes, technically. DNA can be double-stranded or single-stranded. The single-stranded DNA or RNA can be the coding strand, also known as the sense strand, or it can be the non-coding strand, also referred to as the anti-sense strand.

By "isolated" nucleic acid molecules is meant a nucleic acid molecule, DNA or RNA, which can be removed from its native environment. For example, recombinant DNA molecules contained in a vector are considered isolated for the purpose of the present invention. Additional examples of the isolated DNA molecules include recombinant DNA molecules maintained in heterologous host cells or DNA molecules purified (partially or substantially) in solution. Isolated RNA molecules include RNA transcripts from the DNA molecules of the present invention. The nucleic acid molecules isolated according to the present invention also include such synthetically produced molecules.

The isolated nucleic acid molecules of the present invention include DNA molecules comprising an open reading frame (ORF) shown in SEQ. ID NO: 1; the DNA molecules comprising the coding sequence for the mature METH1 protein; and DNA molecules comprising a sequence substantially different from those described above but which, due to the degeneracy of the genetic code, will still encode the METH1 protein. Also included are DNA molecules comprising an open reading frame (ORF) shown in SEQ. ID NO: 3; DNA molecules comprising the coding sequence for the mature METH2 protein; and DNA molecules comprising a sequence substantially different from those described above but which, due to the degeneracy of the genetic code, will still encode the METH2 protein. Of course, the genetic code is well known in the art. Thus, it will be routine for someone with skills in the art to generate such degenerate variants.

In another aspect, the invention provides isolated DNA molecules encoding the METH1 or METH2 polypeptides having an amino acid sequence as encoded by the DNA clones contained in the deposited plasmids as ATCC Deposit No. 209581 of January 15, 1998 or ATCC Deposit No. 209582 on January 15, 1998, respectively. In a further embodiment, the nucleic acid molecules encoding the mature METH1 or METH2 polypeptide or the full length METH1 or METH2 polypeptide lacking the N-terminal methionine are provided. The invention also provides an isolated nucleic acid molecule having the nucleotide sequence shown in SEQ. ID NO: 1 or in the SEC. ID NO: 3 or the sequence of - -nucleotides of the METH1 or METH2 cDNA, - contained in the deposited clones, described above, or a nucleic acid molecule having a sequence complementary to one of the above sequences. Such isolated molecules, particularly DNA molecules, are useful as probes for the generation of genetic maps, by hybridization in itself with chromosomes, and for detecting the expression of the METH1 or METH2 gene in human tissue, for example by analysis of spotting or Northern blotting.

The present invention is further directed to the fragments of the nucleic acid molecules described herein. By a fragment of an isolated nucleic acid molecule having the nucleotide sequence of the deposited cDNA or the sequence of nucleotides shown in SEQ. ID NO: 1 or SEC. ID NO: 3 fragments are indicated at least about 15 nt, and more preferably at least about 20 nt, even more preferably at least - about 30 nt, and even more preferably, at least about 40 nt in length which are useful as useful as diagnostic probes and primers as discussed here. Of course, the largest fragments 50, 100, 150, 200, 250, 300, 350, 400, 450, 500, 550, 600, 650, 700, 750, 800, 850, 900, 950, 1000, 1050, 1100 , 1200, 1300, 1400, 1500, 1600, 1700, 1800, 1900, 2000, 2100, 2200, 2300, 2400, 2500, 2600, 2600, 2700, 2800, 2900, or 3000 nt in length are also useful according to the present invention as are the fragments corresponding, for the most part, if not all, of the nucleotide sequence of the deposited cDNA or as shown in SEQ. ID NO: 1 or in the SEC. ID NO: 3. By fragment of at least 20 nt in length, for example, fragments are indicated which include 20 or more contiguous bases of the nucleotide sequence of the deposited cDNA or the nucleotide sequence as shown in SEQ. ID NO: 1 or in the nucleotide sequence 3.

- - Preferred nucleic acid fragments of the present invention include nucleic acid molecules that encode the epitope-bearing portions of the METH1 or METH2 protein. The methods for determining the portions bearing the epitopes of the METH1 and METH2 proteins are described in detail below.

Other preferred nucleic acid fragments of the present invention include nucleic acid molecules that encode: the metalloprotease domain of METH1, amino acids 235 through 459 in SEQ. ID NO. 2; the disintegrin domain of METHl, amino acids 460 to 544 in the SEC. ID NO. 2; the first domain similar to the TSP of METHl, amino acids 545 to 598 in the SEC. ID NO. 2; the second domain similar to the TSP of METHl, amino acids 841 to 894 in the SEC. ID NO. 2; the third domain similar to the TSP of METHl, amino acids 895 to 934 in the SEC. ID NO. 2; amino acids 536 to 613 in SEC. ID NO. 2; amino acids 549 to 563 in SEC. ID NO. - -2; the metalloprotease domain of METH2, amino acids 214 to 439 in SEC. ID NO. 4; the disintegrin domain of METH2, amino acids 440 to 529 in SEC. ID NO. 4; the first domain similar to the TSP of METH2, amino acids 530 to 583 in the SEC. ID NO. 4; the second domain similar to the TSP of METHl, amino acids 837 to 890 in the SEC. ID NO. 4; amino acids 280 to 606 in SEC. ID NO. 4; amino acids 529 to 548 in SEC. ID NO. Four.

In addition, the present inventors have identified the following cDNA clones related to the portions of the sequence shown in SEQ. ID NO. 1: HOUC17RA (SEQ ID NO: 14), HPLBM11R (SEQ ID NO: 15), HGB107R (SEQ ID NO: 16), HNTMA49R (SEQ ID NO: 17), HNALE27R (SEQ ID NO: 18) ), and HIBDB45R (SEQ ID NO.19).

The following public ESTs, which relate the portions of the SEC. ID NO: 1, have also been identified: D67076 (SEQ ID NO: 20), AB001735 (SEQ ID NO: 21), X14787 (SEQ.

- - ID NO: 22) ',' U64857 (SEQ ID NO: 23), X04665 (SEQ ID NO: 24), M64866 (SEQ ID NO: 25), L07803 (SEQ ID NO: 26), U08006 (SEQ ID NO: 27), M16974 (SEQ ID NO: 28), L13855 (SEQ ID NO: 29), AL021529 (SEQ ID NO: 30), D86074 (SEQ ID NO: 31), L05390 (SEQ ID NO: 32), Z69361 (SEQ ID NO: 33), X99599 (SEQ.

ID NO: 34), AF018073 (SEQ ID NO: 35), L23760 (SEQ ID NO: 36), Z46970 (SEQ ID NO: 37), AC004449 (SEQ ID NO: 38), Z69589 (SEQ.

ID NO: 39), Z22279 (SEQ ID NO: 40), and X17524 (SEQ ID NO: 41).

The present inventors have also identified the following - DNA clones related to the portions of the SEC. ID NO: 3: HCE4D69FP02 (SEQ ID NO: 42), HIBD845F (SEQ ID NO: 43), HKIXH64R (SEQ ID NO: 44), HIBDB45R (SEQ ID NO: 19), HCE3Z95R (SEQ ID NO: 45), HTLEQ90R (SEQ ID NO: 46) , HMWEF45R (SEQ ID NO: 47), HTOFC34RA (SEQ ID NO: 48), HHFDI20R (SEQ ID NO: 49), HMSHY47R (SEQ ID NO: 50), HCESF90R (SEQ ID NO: 51) , HM4CA046R (SEQ ID NO: 52), HTTAQ67R (SEQ ID NO: 53), HFKCF19F (SEQ ID NO: 54), HMCAS31R (SEQ ID NO: 55), HMWGP26R (SEQ ID NO: 56), HLHTP36R (SEQ ID NO: 57), HE8AN11R (SEQ ID NO: 58), HEONN73R (SEQ ID NO: 59), HBNBG53R (SEQ ID NO: 60), and HMSCH94R (SEQ ID NO: 61).

The following public ESTs, which relate the portions of the SEC. ID NO: 3, have also been identified: D67076 (SEQ ID NO: 20), AB001735 (SEQ ID NO: 21), AB005287 (SEQ ID NO: 62), X87619 (SEQ ID NO: 63), X14787 (SEQ ID NO: 22), X04665 (SEQ ID NO: 24), M87276 (SEQ ID NO: 64), M62458 (SEQ ID NO: 65), AB002364 (SEQ ID NO: 66), AB005297 (SEQ ID NO: 67), X69161 (SEQ ID NO: 68), X16619 (SEQ ID NO: 69), 136448 (SEQ ID NO: 70), L12260 (SEQ ID NO: 71), 136352 (SEQ.

ID NO: 72), X15898 (SEQ ID NO: 73), 107789 (SEQ ID NO: 14), 108144 (SEQ ID NO: 75) U31814 (SEQ ID NO: 76), and AF001444 (SEQ ID NO: 77).

In specific embodiments, the polynucleotides of the invention are less than 300 kb, 200 kb, 100 kb, 50 kb, 15 kb, 10-kb, or 7.5 kb in length. In an additional embodiment, the polynucleotides of the invention comprise at least 15 contiguous nucleotides of the coding sequence of METH1 or METH2, but do not comprise all or a portion of any intron of METH1 or METH2. In another embodiment, the nucleic acid comprises the coding sequence of METH1 or METH2, which does not contain the coding sequences of a genomic flanking gene (ie, 5 'or 3' to the METH1 or METH2 gene in the genome).

In another aspect, the invention provides an isolated nucleic acid molecule comprising a polynucleotide that hybridizes under severe conditions of hybridization to a portion of the polynucleotide in a nucleic acid molecule of the invention described above, eg, the cDNA clones contained in the ATCC Deposit No. 209581 or in the ATCC Deposit No. 209582. Through "Severe Hybridization Conditions" incubation is indicated overnight at 42 ° C in a solution comprising: 50% formamide ai, 5x SSC (NaLl 750 IM, 75 m sodium citrate), 50 mM sodium phosphate (pH 7.6), Denhardt 5x solution, 10% dextran sulfate, and 20 μg / ml denatured salmon sperm DNA, followed by the leaching of the filters in SSC O.lx to approximately 65 ° C.

A polynucleotide that hybridizes to a "portion" of a polynucleotide is indicated by a polynucleotide (either DNA or RNA) that hybridizes to at least about 15 nucleotides (nt), and more preferably at least about 20 nt, even more preferably at least about 30 nt, and even more preferably at least 30, 40, 60 or 70 nt of the reference polynucleotide. These are useful as probes and diagnostic primers as discussed above and as will be discussed below below.

Through a portion of a polynucleotide of "at least 20 nt in length", for example, 20 or more nucleotides -contiguous of the nucleotide sequence of the reference polynucleotide (eg, the deposited cDNAs or the nucleotide sequence as shown in SEC ID NO: 1 or SEC ID NO: 3). Of course, a polynucleotide that hybridizes only to a poly A sequence (such as the 3 'terminal poly (A) tract of the METH1 or METH2 cDNA shown in SEQ ID NO: 1 and SEQ ID NO: 3, respectively) or to a complementary portion of the T (or U) residues, would not be included in a polynucleotide of the invention used to hybridize a portion of a nucleic acid of the invention, since such a polynucleotide would hybridize to any nucleic acid molecule that contains a poly (A) portion or the complement thereof (for example, practically any clone of double-strand cDNA).

Also contemplated are nucleic acid molecules that hybridize to METH1 or METH2 polynucleotides at moderately more severe hybridization conditions.

Changes in hybridization severity and signal detection are complemented mainly by manipulation of formamide concentration (lower percentages of formamide result in lower severity, saline conditions, or temperature. of moderately more severe hybrids include an overnight incubation at 37 degrees C in a solution comprising 6X SSPE (20X SSPE = 3M NaCl, 0.2M NaH2P0, 0.02M EDTA, pH 7.4), SDS at 0. 5%, 30% formamide, 100 μg / ml of salmon sperm DNA blocking; followed by washes at 50 ° C with SSPE IX, 0.1% SDS. In addition, to achieve even a lower severity, the washes are carried out following the severe hy- draization that can be done at high salt concentrations (for example SSC 5X).

Note that variations in the above conditions can be complemented through the inclusion and / or substitution of alternative blocking reagents - used to suppress background in the hyphenation experiments. Typical blocking reagents include Denhardt's reagent, BLOTTO, heparin, denatured salmon sperm DNA, and commercially available brand formulations. The inclusion of specific blocking and blocking reactions may require modification of the hybridization conditions described above, due to problems with compatibility.

Of course, a polynucleotide that hybridizes only to the polyA + sequences (such as the polyA + 3 'terminal tract of a cDNA shown in the sequence listing), or to a complementary portion of the T (or U) residues, would not be included in the definition of the "polynucleotide", since such a polynucleotide would hybridize to any nucleic acid molecule that contains a poly (A) moiety or the complement thereof (e.g., virtually any double-stranded cDNA clone).

The polynucleotide METH1 and METH2 can be composed of any polynucleotide or po1 ide or ox i r r ibon c 1 that can be unmodified RNA or DNA or modified RNA or DNA. For example, METH1 or METH2 polynucleotides can be composed of single-stranded, or double-stranded DNA, DNA that is a mixture of the single-stranded and double-stranded regions, single-stranded, double-stranded RNA, and RNA that be the mixture of the single-stranded and double-stranded regions, the hybrid molecules comprising DNA and RNA that can be a single strand or, more typically, the double-stranded regions or a mixture of one strand and double strand. In addition, the METH1 or METH2 polynucleotides may be composed of the triple-stranded regions comprising RNA or DNA or both RNA and DNA. The METH1 or METH2 polynucleotides may also contain one or more modified bases or DNA or RNA backbones modified for stability or for other reasons. "Modified" bases include, for example, tritilized bases and non-usual bases such as inosine. A variety of modifications can be made to DNA and RNA; thus, the "polynucleotide" encompasses the chemically, enzymatically, or metabolically modified forms.

"SEC ID NO: 1" refers to the polynucleotide sequence METH1 while "SEC ID O: 2" refers to a sequence of the METH1 polypeptide. "SEQ ID NO: 3 refers to a sequence of the METH2 polypeptide while" SEC. ID NO: - 4"refers to a sequence of the METH2 polypeptide.

As indicated, the nucleic acid molecules of the present invention that encode a METH1 or METH2 polypeptide, but are not limited, to those encoding the amino acid sequence of the mature polypeptide, by itself, the coding sequence for the mature polypeptide and additional sequences, such as those encoding the leader or secretory sequence, such as the sequence of pre-, or pro- or prepr-pr ote, the coding sequence of the mature polypeptide, with or without the sequences of additional coding mentioned above, together with the additional non-coding sequences, including but not limited to sequences of introns and 5 'and 3' non-coding sequences, such as untranslated, transcribed sequences, which play a role in the transcription, mRNA processing, which includes the polyadenylation and splicing signals, for example, - the link to the ribosome and the stabili mRNA quality; an additional coding sequence that encodes the additional amino acids, such as those that provide additional functionalities. Thus, the sequence encoding the polypeptide can be fused to a marker sequence, such as a sequence encoding a peptide that facilitates purification of the fused polypeptide. In certain preferred embodiments of this aspect of the invention, the marker amino acid sequence is a hexa-histidine peptide, such as the indicator or label provided in a pQE vector (Qiagen, Inc.), among others, many of which are commercially available. As described in Gentz et al. , Proc. Natl. Acad. Sci. USA 86: 821-824 (1989), for example, hexa-histidine provides convenient purification of the fusion protein. The "HA" mark is another peptide useful for purification corresponding to an epitope derived from the influenza hemagglutinin protein, which has been described by Wilson et al. Cell 37: 767-778 (1984). As will be discussed below, another such fusion protein includes METH1 or METH2 fused to Fc in the N- or C-t e rmi nals.

The present invention also relates to variants of nucleic acid molecules, which encode portions, analogs or derivatives of the METH1 or METH2 protein. Variants can occur naturally, such as a natural allelic variant. By means of an "allelic variant" one of several alternative forms of - a gene that occupies a given place in a chromosome of an organism is indicated. Lewin, B., ed., Ge n e s I I, John Wiley & Sons, New York (1985). Variants that occur unnaturally can be produced using mutagenesis techniques known in the art.

Such variants include those produced by substitutions eliminations or additions of nucleotides, which may involve one or more nucleotides. The variants may be altered in the coding regions, in the non-coding regions, or both. Alterations in the coding regions can produce their substitutions, deletions or additions of conservative or non-conservative amino acids. Especially preferred among these are the silent substitutions, additions and deletions, which do not alter the properties and activities of the METH 3 or METH2 protein or portions thereof. Also, conservative substitutions are especially preferred in this regard.

- - Additional embodiments of the invention include isolated nucleic acid molecules comprising a polynucleotide having at least 95% identical nucleic acid sequence and more preferably at least 96%, 97%, 985 or 99% identical to: a nucleotide sequence encoding the polypeptide having the amino acid sequence in SEQ. ID NO: 2; a nucleotide sequence encoding the polypeptide having the amino acid sequence in SEQ. ID NO: 2, but lacking the N-terminal methionine; a nucleotide sequence encoding the polypeptide having the amino acid sequence at positions from about 29 to about 950 in SEQ. ID NO: 2; a nucleotide sequence encoding the polypeptide having the amino acid sequence in the position from about 30 to about 950 in SEQ. ID NO: 2; a nucleotide sequence encoding the polypeptide having the sequence of α-amino acids encoded by the cDNA clone contained in ATCC Deposit No. 209581; a nucleotide sequence encoding the mature METH1 polypeptide having the amino acid sequence encoded by the cDNA clone contained in ATCC Deposit No. 209581; a nucleotide sequence encoding amino acids 235 to 459 in SEQ. ID NO: 2 (the metalloprotease domain of METHl); a nucleotide sequence encoding amino acids 460 to 544 in SEQ. ID NO: 2 (the disintegrin domain of METHl); a nucleotide sequence encoding amino acids 545 to 598 in SEQ. ID NO: 2 (the first domain similar to the TSP of METHl); a nucleotide sequence encoding amino acids 841 to 894 in SEQ. ID NO. 2 (the second domain similar to the METHl TSP); a nucleotide sequence encoding amino acids 895 to 934 in SEQ. ID NO. 2 (the domain similar to the third TSP of the METHl); a nucleotide sequence encoding amino acids 536 to 613 in SEQ. ID NO. 2; a nucleotide sequence encoding amino acids 549 to 563 in l-a SEC. ID NO. 2; a nucleotide sequence encoding the polypeptide having the amino acid sequence in SEQ. ID NO: 4; a nucleotide sequence encoding the polypeptide having the amino acid sequence in SEQ. ID NO: 4, but lacking the N-terminal methy nine; a nucleotide sequence encoding the polypeptide having the amino acid sequence at positions from about 24 to about 890 in SEQ. ID NO: 4; a nucleotide sequence encoding the polypeptide having the amino acid sequence at positions from about 112 to about 890 in SEQ. ID NO: 4; a nucleotide sequence encoding the polypeptide having the amino acid sequence encoded by the cDNA clone contained in ATCC Deposit No. 209582; a nucleotide sequence encoding the mature METH2 polypeptide having the amino acid sequence encoded by the cDNA clone contained in the ATCC-No Deposit. 209582; a nucleotide sequence encoding amino acids 214 to 439 in SEQ. ID NO: 4 (the metalloprotease domain of METH2); a nucleotide sequence encoding amino acids 440 through 529 in SEQ. ID NO: 4 (the disintegrin domain of METH2); a nucleotide sequence encoding amino acids 530 through 583 in SEQ. ID NO: 4 (the first domain similar to the TSP of METH2); a nucleotide sequence encoding amino acids 837 to 890 in SEQ. ID NO. 4 (the second domain similar to the TSP of METH2); a nucleotide sequence encoding amino acids 280 to 606 in the - SEC. ID NO. 4; a nucleotide sequence encoding amino acids 529 to 548 in SEQ. ID NO. 4; or a nucleotide sequence complementary to any one of the sequences of the above nucleotides.

By a polynucleotide having a nucleotide sequence at least, for example, 95% "identical" to a reference nucleotide sequence encoding the METH1 or METH2 polypeptide, it is indicated that the nucleotide sequence of the polynucleotide is identical to the reference sequence except that the polynucleotide sequence may include up to five mutation points per 100 nucleotides of the reference nucleotide sequence encoding the METH1 or METH2 polypeptide. In other words, to obtain a polynucleotide having a nucleotide sequence at least 95% identical to a reference nucleotide sequence, up to 5% of the nucleotides in the reference sequence can be deleted or replaced with another nucleotide, or a number of nucleotides up to 5% of the total nucleotides in the reference sequence can be inserted into the reference sequence. These mutations of the reference sequence can occur at the 5 'or 3' terminal positions of the reference nucleotide sequence or anywhere between those terminal positions, interspersed either individually between the nucleotides in the reference sequence or in - one or more of the contiguous groups within the reference sequence.

As a practical matter, if any particular nucleic acid molecule is at least 95%, 96%, 97%, 98%, or 99% identical to, for example, the nucleotide sequence shown in SEQ. ID NO: 1 or in the SEC. ID NO: 3 or the nucleotide sequence of the deposited cDNA clones can be determined conditionally using known computer programs such as the Bestfit Program (Wisconsin, Sequence Analysis, Version 8 for Unix, Genetics Computer Group, University Research Park, 575 Science Drive, Madison, Wl 53711). The Bestfit uses the local homology algorithm of Smith and Waterman, A d va n ce s i n App l i e d Ma th ema t i cs 2: 482-489 (1981), to find the best homology segment between the two sequences. When the Bestfit or any other sequence alignment program is used to determine whether a particular sequence is, for example, 95% identical to a reference sequence according to the present invention, the parameters are, of course, fixed such that the percent identity is calculated over the entire length of the reference nucleotide sequence and that spaces or separations are allowed in the homology of up to 5% of the total number of nucleotides in the reference sequence.

A preferred method for determining the best total match between a reference sequence (a sequence of the present invention) and an objective sequence, also referred to as a global sequence alignment, can be determined using the FASTDB computer program based on the algorithm of Brutlag et al. C omp. App l. B i o s ci. 6: 2 3 1 - 2 4 5 (1990). In a sequence alignment, the reference and target sequences are both DNA sequences. An RNA sequence can be compared by converting the U to the T. The result of such global sequence alignment is a percent identity. The preferred parameters used in an alignment of --FASTDB of the DNA sequences to calculate the percent identity are: Matrix = Unitary, k-tuple = 4, Penalty for non-Pairing = 1, Penalty for Union = 30, Group Length Randomization = 0, Court Record = 1, Penalty by Separation = 5, Penalty by Size of Separation = 0.05, Window Size = 500 or the length of the target nucleotide sequence, even if it is shorter.

If the target sequence is shorter than the reference sequence due to 5 'or 3' eliminations, not due to internal deletions, a manual correction to the results must be made. This is because the FASTDB program does not count the 5 'and 3' truncations of the target sequence when the percent identity is calculated. For the target sequences truncated at the 5 'or 3' ends, in relation to the reference sequence, the identity percentage is corrected by calculating the number of bases of the reference sequence that are 5 'and 3' of the sequence. - -objective, which do not mate 1 inean, as a percentage of the total bases of the reference sequence. If it is determined that a nucleotide is paired / aligned by the results of the alignments of the FASTDB sequence. This percentage is subtracted from the identity percentage, calculated by the previous FASTDB program using the specified parameters, to arrive at a final percentage identity record. This corrected record is what is used for the purpose of the present invention. Only the outer bases of the 5 'and 3' bases of the target sequence, as shown by the alignment of the FASTDB, which do not appear with the reference sequence are calculated for the purposes of manually adjust the percentage identity record.

For example, a target sequence of 90 bases is aligned to a reference sequence of 100 bases to determine percent identity. The deletions occur at the 5 'end of the target sequence and, for example, the FASTDB alignment does not show an ap h e n t i / a 1 i n ea c i of the first 10 bases at the 5' end. The 10 unpaired bases represent 10% of the sequence (number of bases at the 5 'and 3' ends not ap eared s / total number of bases in the reference sequence), so that 10% is subtracted of the identity percentage record calculated by the FASTDB program. If the remaining 90 bases mate perfectly, the identity of the final percentage would be 90%. In another example, a target sequence of 90 bases is compared to a reference sequence of 100 bases. This time the eliminations are internal, so that there are no bases at the 5 'or 3' ends of the target sequence that are not mapped to 1 s with the reference. In this case, the identity percentage calculated by the FASTDB is not corrected manually. Again, only the 5 'and 3' bases of the target sequence that are unpaired 1 with the reference sequence are manually corrected. No other manual correction is made for the purpose of the present invention.

The present application is directed to the nucleic acid molecules at least 95%, 96%, 97%, 98% or 99% identical to the nucleic acid sequence shown in FIG.

SEC. ID NO or SEQ ID NO or the nucleic acid sequence of the deposited cDNAs, without taking into account whether they code for a polynucleotide having the activity of METH1 or METH2. This is because even when a particular nucleic acid molecule does not encode a polypeptide having the METH1 or METH2 activity, one skilled in the art will know how to use the nucleic acid molecule, for example, as a hybridization probe or a polymerase chain reaction primer (PCR). Uses of the nucleic acid molecules of the present invention that do not encode a polypeptide having the METH1 or METH2 activity include, i n t e r a l a, (1) isolating the METH1 or METH2 gene or allelic variants thereof in a cDNA library; (2) in situ hybridization (for example to extend the chromosomal metaphase to provide an accurate localization of the chromosomes of the METH1 or METH2 gene, as described in Verma et al., Human Chromosomes: A Manual of Basic Techniques, Pergamon Press , New York (1988); and (3) Northern Blot Analysis to detect the expression of METH1 or METH2 mRNA in specific tissues.

However, nucleic acid molecules having at least 95%, 96%, 97%, 98% or 99% sequences identical to the nucleic acid sequence shown in SEQ. ID NO: 1 or SEC. ID NO: 3 or a nucleic acid sequence of the deposited cDNAs, which in fact encodes a polypeptide having the activity of the METH1 or METH2 protein. By "a polypeptide having the METH1 activity" the polypeptides showing the METH1 activity in a particular biological assay are indicated. For example, the activity of the METH1 protein can be measured using the chorioallantoic membrane assay (I ruela-Ar i spe et al., Thrombosis and Haemostasis 78 (1): 672-677 1997)) or the corneal pocket assay (Tolsma et al., J. Cell, Biol. 122: 491-511 (1993)), both described in Example 4, below. By "a polypeptide having the METH2 activity" the polypeptides showing the METH1 activity in a particular biological assay are indicated. For example, the activity of the METH2 protein can be measured using the chorioallantoic membrane assay (I r ue la-Arispe et al., Thrombosis and Haemostasis 78 (1): 612-677 1997)) or the corneal pocket assay (Tolsma et al., J. Cell, Biol. 122: 491-511 (1993)), both described in Example 4, below.

Briefly, in the chorioallantic assay, the potentially anti-angiogenic compound of interest is added to the pellets of type I collagen (Vitrogen), together with an angiogenic growth factor, such as bFGF. The samples are mixed and placed in nylon meshes, and allowed to polymerize. After the polymerization is complete, the meshes are placed on the chorioallantoic membrane of embryos of 12-day-old chickens and placed at 37 ° C for 24 hours. The embryos are then injected with a fluorescent agent, such as FITC -dex tantum, and the meshes are fixed and mounted for observation under a fluorescent microscope.

In the corneal pocket assay, the hydron pellets containing the compound of interest and an angiogenic growth factor, such as bFGF, are implanted 1 to 2 mM from the limb of the cornea of rats or mice. The answer is examined after a period of time, for example 5 days. The extent of angiogenesis is evaluated by measuring the migration of the capillaries from the limbus of the cornea.

Of course, due to the degeneracy of the genetic code, someone with ordinary skill in the art will immediately recognize that a large number of the nucleic acid molecules having a sequence at least 95%, 96%, 97%, 98 % or 99% identical to the nucleic acid sequence of the deposited cDNAs or a nucleic acid sequence shown in SEQ. ID NO: 1 or SEC. ID NO: 3 will encode a polypeptide "having the activity of the METH1 or METH2 protein". In fact, since the degenerate variants of these nucleotide sequences encode all of the same polypeptide, it will be very clear to the person skilled in the art even without performing the comparison test described above. It will be further recognized in the art that, for such nucleic acid molecules that are not degenerate variants, a reasonable number also encodes a polypeptide having the activity of the METH1 or METH2 protein. This is because the technician skilled in the art will be fully aware of amino acid substitutions that are either less significant or more significant in the effect of protein function (for example, replacing an aliphatic -amino acid with a second aliphatic amino acid).

For example, a guide concerning how to make substitutions of phenotypically silent amino acids is provided in Bowie, J. U. et al. "Deciphering the Message in Protein Sequences: Tolerance to Amino Acid Substitutions," Science 247: 1306-131 (1990), where the authors indicate that proteins are surprisingly tolerant of amino acid substitutions.

Vectors and Host Cells or Hosts The present invention also relates to vectors that include the isolated DNA molecules of the present invention, the host cells or hosts that are engineered with the recommanant vectors, and the production of the METH1 or METH2 polypeptides or fragments thereof. themselves by recombinant techniques.

- The polynucleotides can be linked to a vector containing a selectable marker for propagation in a host or host. In general, a plasmid vector is introduced into a precipitate, such as a calcium phosphate precipitate, or into a complex with a charged lipid. If the vector is a virus, it can be packaged using a line of appropriate packaging cells and then transduced into host cells or hosts.

The DNA insert should be operably linked to an appropriate promoter, such as a phage promoter "lambda PL, E. colilac, t rp and tac promoters, SV40 early and late promoters and retroviral LTR promoters, to name a few. Other suitable promoters are known to those skilled in the art Expression constructs will additionally contain sites for the initiation, termination of transcription and, in the transcribed region, a ribosome binding site for translation. -codification of the mature transcripts expressed by the constructs will preferably include a start translation codon at the start and a stop codon (UAA, UGA or UAG) appropriately placed at the end of the polypeptide to be translated.

As indicated, the expression vectors will preferably include at least one selectable marker. Such markers include dihydrofolate reductase or neomycin resistance for the culture of eukaryotic cells and the tetracycline or ampicillin resistance genes for cultures in E. coli and other bacteria. Representative examples of appropriate hosts include, but are not limited to, bacterial cells such as E. coli, Streptomyces and Salmonella t cells and p h i mu r i m; fungal cells, such as yeast cells; insect cells such as Drosophila S2 and Spodoptera Sf 9 cells; animal cells such as CHO, COS and --Bowes melanoma cells; and plant cells. The appropriate culture media and conditions for the host cells described above are known in the art.

The preferred vectors for use in bacteria include pQE70, pQE60 and pQE-9, available from Qiagen; pBS vectors, Phagescript vectors, Bluescript vectors, pNH8A, pNHl6A, pNH18A, pNH46A, available from Stratagene; and ptrc99a, pKK223-3, pKK233-3, pDR540, pRIT5 available from Pharmacia. Among the preferred eukaryotic vectors are pWLNEO, pSV2CAT, pOG44, pXT1 and pSG available from Stratagene; and pSVK3, pBPV, pMSG and pSVL available from Pharmacia. Other suitable vectors will be readily apparent to one skilled in the art.

In addition to the use of expression vectors in the practice of the present invention, the present invention further includes novel expression vectors comprising the elements of the operator and the promoter operably linked to the nucleotide sequences encoding a protein of interest. An example of such a vector is pHE4-5, which is described in more detail below.

As summarized in Figures 8 and 9, the components of the vector pHE4-5 (SEQ ID NO: 12) include: 1) a gene for e ffi ciency e ffi cients as a selection marker, ) an origin of E. c or l i of replication, 3) a phage promoter sequence T5, 4) two sequences of the operator l a c, 5) a Shine-Del garno sequence, 6) the repressor gene of the lactose operon (laclq). The origin of replication (oriC) is derived from pUC19 (LTI, Gaithersburg, MD). The promoter sequence and operator sequences are manufactured synthetically. The synthetic production of the nucleic acid sequences are well known in the art. CLONTECH Catalog 95/96, pages 215-216, CLONTECH, 1020 East Meadow Circle, Palo Alto, CA 94303. A nucleotide sequence encoding METH1 (SEQ ID NO: 2) or METH2 (SEQ ID NO: 4), is operatively linked to the promoter and the operator by inserting the nucleotide sequence between the Ndel and Asp718 sites of the vector pHE4-5.

As noted above, vector pHE4-5 contains a Jaclq gene. The laclq is an allele of the lacl gene that confers a tight regulation of the lac operator. Amann, E. et al. , Gene 59: 301-315 (1988); Stark, M., Gene 51: 255-261 (1987). The laclq gene encodes a repressor protein that binds to the lac operator sequences and blocks the transcription of 'sequences in the 3' direction. However, the product of the laclq gene is dissociated from the lac operator in the presence of either lactose or certain lactose analogs, for example, B-D-thioga lact opiate isopropyl ida (IPTG). Therefore METH1 or METH2 are not produced in appreciable amounts in uninduced host cells that contain the vector pHE4-5. The induction of these host cells by the addition of an agent such as IPTG, however, results in the expression of the coding sequence of METH1 or METH2.

The sequences of the p ror t o r / op e ra te r of the vector pHE4-5 (SEQ ID NO: 13) comprises a phage T5 promoter and two operator sequences l a c. One operator is located at the 5 'end to the transcription start site and the other is located at the 3' end at the same site. These operators, when present in combination with the product of the laclq gene, they confer a hermetic repression of the sequences in the 3 'direction in the absence of an inducer of the operon l to c, for example, IPTG. The expression of the linked sequences operatively located in the 3 'direction of the operators l a c se. it can be induced by the addition of an inducer of the operon l to c, such as IPTG. The binding of an inducer to the laclq proteins results in their release from the operant sequences l a c and the initiation of transcription of the operably linked sequences. The - regulation of the operon l a c of gene expression is reviewed in Devlin, TEXTBOOK OF BIOCHEMISTRY WITH CLINICAL CORRELAT I ONS, 4a. Edition - (1997), pages 802-807.

The pHE4 series of the vectors contain all the components of the pHE4-5 vector except for the coding sequence of METH1 or METH2. The characteristics of the pHE4 vectors include the optimized synthetic T5 phage promoter, the operator l a c, and the sequences S h i n e - De 1 ga rno. In addition, these sequences are also optimally so that the expression of an inserted gene can be regulated in a very stable manner and the high level of expression occurs after induction.

Suitable bacterial promoters suitable for use in the production of the proteins of the present invention include the lacZ and laclq promoters of E. c or l i, the T3 and T7 promoters, the gp t promoter, the PR and PL lambda promoters and the trp promoter. Suitable eukaryotic promoters include the CMV immediate early promoter, the HSV thymidine kinase promoter, the SV40 early and late promoters, the retroviral LTR promoters, such as those of the Rous Sarcoma Virus (RSV), and the promoters of metallothionein, such as the mouse 1 oti one nina-1 promoter.

The vector pHE4-5 also contains the 5 'sequence of S h i n e - From 1 g a r n o to the initiation codon AUG. The Shi ne-Del ga rno sequences are short sequences located generally around 10 nucleotides in the di ff ect 5 'from the initiation codon AUG. These sequences are directed essentially to prokaryotic ribosomes at the AUG initiation codon.

Thus, the present invention is also directed to the expression vector useful for the production of the proteins of the present invention. This aspect of the invention is exemplified by the vector pHE4-5 (SEQ ID NO: 12).

- - The introduction of the construct into the host cells can be effected by calcium phosphate transfection, DEAE-dextran-mediated transfection, cationic lipid-mediated transfection, electroporation, transduction, infection or other methods. Such methods are described in many standard laboratory manuals, such as Davis et al. , Basic Methods in Molecular Biology (1986).

The polypeptide can be expressed in a modified form, such as a fusion protein, and can include or only the secretion signals, but also the additional heterologous functional regions. For example, a region of additional amino acids, particularly charged amino acids, can be added to the N-terminus of the polypeptide to improve stability and persistence in the host or host cell, during purification, or during handling or subsequent storage. Also, portions of the peptide can be added to the polypeptide to facilitate purification. Such regions can be removed before the final preparation of the polypeptide. The addition of portions of the peptide to the polypeptides to generate secretion or excretion, to improve stability and facilitate purification, among others, are familiar and routine techniques in the art. The preferred fusion protein comprises a heterologous region of the immunoglobulin which is useful for solubilizing the proteins. For example, EP-A-0 464 533 (Canadian Counterpart 2045869) describes the fusion proteins comprising several portions of the immunoglobulin molecules together with another human protein or part thereof. In many cases, the Fc-part in a fusion protein is completely advantageous for use in therapy and diagnosis and results, for example, in improved pharmacokinetic properties (EP-A 0232 262). On the other hand, for some uses it would be desirable to be able to remove the Fc cloth after the fusion protein has been expressed, detected and purified in the advantageous manner described. This is the case when the Fc portion proves to be an excellent material for use in therapy and diagnosis, for example when the fusion protein is to be used as an antigen for immunizations. In drug discovery, for example, human proteins, such as the hIL-5 receptor, have been fused with the Fc portions for the purpose of high throughput screening assays to identify hIL-5 antagonists. See, D. Bennett et al. , J. Mol. Recognition 8: 52-58 (1995) and K. Johanson et al., J. of Biol. Chem. 270 (16): 9459-9411 (1995).

The METH1 or METH2 protein can be recovered and purified from recombinant cell cultures by well-known methods, including precipitation with ammonium sulfate or ethanol, acid extraction, anionic or cation exchange chromatography, chromatography with fos focelulosa, hydrophobic interaction chromatography, affinity chromatography, - the chromatography of h idr oxi lap atit and chromatography with lectin. More preferably, high performance liquid chromatography ("HPLC") is used for purification. The polypeptides of the present invention include the naturally purified products, the products of synthetic chemical processes, and the products produced by recombinant techniques of a prokaryotic or eukaryotic host, including, for example, bacterial, yeast, higher plant, insects and mammals. Depending on the host or host in a recombinant production method, the polypeptides of the present invention can be glycosylated or non-glycosylated. In addition, the polypeptides of the invention may also include a modified methionine residue, in some cases as a result of the processes mediated by a host.

- -Pol ipép ti do and Fra gm en t o s of ME THl and METH2 The invention further provides an isolated METH1 polypeptide having the amino acid sequence encoded by the deposited cDNA, or the amino acid sequence in SEQ. ID NO: 2, or a peptide or polypeptide comprising a portion of the above polypeptides. The invention also provides an isolated METH2 polypeptide having the one encoded by the deposited cDNA, or the amino acid sequence in SEQ. ID NO: 4, or a peptide or polypeptide comprising a portion of the above polypeptides.

The METH1 and METH2 polypeptides can be composed of amino acids linked together by peptide bonds or modified peptide bonds, i.e., peptide isosteres, and can contain amino acids, other than the amino acids encoded by 20 genes. The METH1 or METH2 polypeptides can be modified either by natural processes, such as post-translational processing, or by. chemical modification which are well known in the art. Such modifications are well described in the basic texts and in more detailed monographs, as well as in some voluminous research literature. Modifications can occur anywhere in the METH1 or METH2 polypeptide, which include the structural chain of the peptide, the side chains of amino acids and the amino or carboxyl termini. It will be appreciated that the same type of modification may occur to the same degree or in varying degrees at several sites in a METH1 or METH2 polypeptide. Also, the given polypeptide METH1 or METH2 can contain various types of modifications. The METH1 or METH2 polypeptides can be branched, for example, as a result of the ubiquity, and can be cyclic, with or without branching. The cyclic, branched, and branched cyclic polypeptides of METH1 or METH2 can result in natural post-translational processes or can be prepared by synthetic methods. Modifications include acetylation, acylation, ribosylation with ADP, amidation, covalent binding of flavin, covalent attachment of a heme moiety, covalent attachment of a nucleotide or nucleotide derivative, covalent attachment of a lipid or lipid derivative, covalent attachment of phosphate idi linos i tol, crosslinking, cyclization, formation of disulfide bonds, smelling 1, formation of covalent cross-links, formation of cysteine, formation of pirog 1 ut ama to, formylation, gamma carboxylation, glycosylation, formation of the anchor GPI , hydroxylation, iodination, methylation, my reaction 1, oxidation, pegylation, proteolytic processing, phosphorylation, prenylation, racemization, seizure, sulfation, RNA-mediated addition of amino acids to proteins as the arginilación, and ubiqui t inacíón. (See, for example, PROTEINS-STRUCTURE AND MOLECULAR PROPERTIES, 2nd Ed., T. E. Creighton, W. H. Freeman and Company, New York, 1993); PO S TTRANS LAT I ONAL COVALENT MODIFICATION OF PROTEINS, B. C. Johnson, Ed., -Academic Press, New York, p. 1-12 (1983); Seifter et al. , Meth. Enzymol 182: 626-646 (1990); Rattan et al. , Ann NY Acad Sci 663: 48-62 (1992)).

It will be recognized in the art that some amino acid sequences of the METH1 and METH2 polypeptides can vary without significant effect of the structure or function of the protein. If such differences in the sequence are contemplated, it should be remembered that there will be critical areas in the protein that determines the activity.

The present inventors have shown that METH1 and METH2 inhibit angiogenesis in vitro and in vivo. The METH1 and METH2 each contain a metalloprotease domain, a disintegrin domain, TSP-like domains. The metalloprotease domain can be catalytically active. The domain of disintegrin may play a role in inhibiting angiogenesis by interacting with integrins, since integrins, since integrins are essential for the -mediation of both proliferative and migratory signals. The present inventors have shown that peptides derived from the TSP-like domains of METH1 and METH2 inhibit angiogenesis i n vi t ro e i n vi v o Thus, the invention further includes variations of the METH1 polypeptide that show substantial METH1 polypeptide activity or that include regions of the METH1 protein such as the portions of the protein discussed below; and variations of the METH2 polypeptide that show substantial METH2 polypeptide activity or that include regions of the METH2 protein such as the portions of the proteins discussed below. Such mutants include deletions, insertions, inversions, repetitions, and substitutions of type. As indicated above, guidance concerning amino acid changes that can be phenotypically silent is found in Bowie, J. U. et al. "Deciphering the Message in Protein Sequences: Tolerance to Amino Acid - Substitutions S ci en ce '24 7: 1 3 0 6 - 13 1 (1990) Thus, the fragment, derivative or analogue of the polypeptide of SEQ. ID NO: 2 or the SEC. ID NO: 4, or that encoded by the deposited cDNA, can be (i) one in which one or more of the amino acid residues are suitably bound with an amino acid residue, conserved or non-conserved (preferably residues). of conserved amino acids) and such a substituted amino acid residue may or may not be encoded by the genetic code, or (ii) one in which one or more of the amino acid residues include a substituent group, or (iii) one in which the mature polypeptide is fused to another compound, such as a compound to increase the half-life of the polypeptide (e.g. polyethylene glycol), or (iv) one in which the additional amino acids are fused to the mature polypeptide, such as a peptide region of IgG Fc fusion or the leader or secretory sequence or a sequence that is employed for the purification of the mature -polypeptide or a proprotein sequence. Such fragments, derivatives and analogs are considered to be within the scope of those skilled in the art from the teachings herein.

Of particular interest are substitutions of charged amino acids with other charged amino acids and with neutrally or negatively charged amino acids. The latter results in proteins with reduced positive charge to improve the characteristics of METH1 or METH2 proteins. The prevention of aggregation is highly desirable. The aggregation of the proteins not only results in a loss of activity but can also be problematic when preparing the pharmaceutical formulations, because they can be immunogenic. (Pinckard et al., Clin. Exp. Immunol., 2: 331-340 (1967); Robbins et al., Diabetes 3: 838-345 (1987); Cleland et al., Crit. Rev. Therapeutic Drug Carrier Systems 10 : 301-311 (1993)). - 1 - As indicated, the changes are preferably of a minor nature, such as the preservative substitutions of amino acids that do not significantly affect the expression or activity of the protein (see Table 3).

Table 3: Conservative Substitutions of Amino Acids - - Of course, the number of amino acid substitutions for a technique in the art may depend on many factors, including those described above. Generally speaking, the number of amino acid substitutions for any given METH1 or METH2 polypeptide will not be more than 50, 40, 30, 20, 10, 5 or 3.

The amino acids in the METH1 and METH2 proteins of the present invention that are essential for function can be identified by methods known in the art, such as site-directed mutagenesis or alanine scanning mutagenesis (Cunningham and Wells, S cience 2 4 4: 1081-1085 (1989)). The last procedure introduces unique alanine mutations in each residue in the molecule. The resulting mutant molecules are then tested for biological activity such as the inhibition of angiogenesis in vi t r o or in vi vi. Sites that are critical for the inhibition of angiogenesis can also be determined by structural analysis such as crystallization, nuclear magnetic resonance or photoaffinity labeling (Smith et al., J. Mol. Biol. 224: 899-904 ( 1992) and de Vos et al., Science 255: 306-312, (1992)).

The polypeptides of the present invention are preferably provided in an isolated form. By "isolated polypeptide" is meant a polypeptide removed from its natural environment. Thus, a polypeptide produced and / or contained within a host cell or recombinant host is considered isolated for the purposes of the present invention. Also indicated as an "isolated polypeptide" are polypeptides that have been purified, partially or substantially, from a recombinant host cell or from a native source. For example, a recombinantly produced version of the METH1 or METH2 polypeptide can be substantially purified by the one step method described in Smith and Johnson, Gene-6 7: 31-4 O (1988) The polypeptides of the present invention include the METH1 polypeptide encoded by the deposited cDNA that includes the leader; the mature METH1 polypeptide encoded by the deposited cDNA minus the leader (i.e., the mature protein); a polypeptide comprising amino acids from about 1 to about 950 in SEQ. ID NO: 2, a polypeptide comprising amino acids from about 2 to about 950 in SEQ. ID NO: 2, a polypeptide comprising amino acids from about 29 to about 950 in SEQ ID NO: 2, a polypeptide comprising amino acids from about 30 to about 950 in SEQ ID NO: 2, a polypeptide which comprises the metalloprotease domain of METH1, amino acids 235 to 459 in SEQ ID NO: 2, a polypeptide comprising the disintegrin domain of METH1, amino acids 460 to 544 in SEQ ID NO. 2, a polypeptide comprising the first-domain similar to the TSP of METH1, amino acids 545 to 598 in SEQ ID NO: 2, a polypeptide comprising the second domain similar to the TSP of METH1, amino acids 841 a 894 in SEQ ID NO: 2, a polypeptide comprising third the TSS-like domain of METH1, amino acids 895 to 934 in SEQ ID NO: 2, a polypeptide comprising amino acids 536 to 613"in the SEC. ID NO. 2; a polypeptide comprising amino acids 549 to 563 in SEQ. ID NO. 2 the METH2 polypeptide encoded by the deposited cDNA that includes the leader; the mature METH2 polypeptide encoded by the deposited cDNA minus the leader (i.e., the mature protein); a polypeptide comprising amino acids from about 1 to about 890 in SEQ. ID NO: 4, a polypeptide comprising amino acids from about 2 to about 890 in SEQ. ID NO: 4, a polypeptide comprising amino acids from about 24 to about 890 in SEQ. ID NO: 4, a polypeptide comprising the α-amino acids from about 112 to about 890 in SEQ. ID NO: 4, a polypeptide comprising the metalloprotease domain of METH2, amino acids 214 to 439 in SEQ. ID NO. 4; a polypeptide comprising the disintegrin domain of METH2, amino acids 440 through 529 in SEQ. ID NO. 4; a polypeptide comprising the first domain similar to the TSP of METH2, amino acids 530 to 583 in SEQ. ID NO. 4; a polypeptide comprising the second domain similar to the TSP of METH2, amino acids 837 to 890 in SEQ. ID NO. 4; a polypeptide comprising amino acids 280 to 606 in SEQ. ID NO. 4; a polypeptide comprising amino acids 529 to 548 in SEQ. ID NO. 4; as well as polypeptides that are at least 95% identical, and more preferably at least 96%, 97%, 98% or 99% identical to the polypeptides described above, and also includes portions of such polypeptides with at least 30 amino acids and more preferably at least 50 amino acids.

By a polypeptide having at least one amino acid sequence, for example, 95% "identical" to a reference amino acid sequence of a METH1 or METH2 polypeptide, it is indicated that the amino acid sequence of the polypeptide is identical to the sequence of reference except that the polypeptide sequences may include up to five amino acid alterations per 100 amino acids of the reference amino acids of the METH1 or METH2 polypeptide. In other words, to obtain a polypeptide having an amino acid sequence at least 95% identical to a reference amino acid sequence, up to 5% of the amino acid residues -in the reference sequence can be eliminated ring substitute with other amino acids, or a number of amino acids up to 5% of the total amino acid residues in the reference sequence can be inserted into the reference sequence. These alterations of the reference sequence may occur at the amino or carboxy terminal positions of the reference amino acid sequence or at any place between those terminal positions, dispersed either individually between the residues in the reference sequence or in one or more contiguous groups within the reference sequence.

As a practical matter, if any particular polypeptide is at least 95%, 96%, 97%, 98% or 99% identical to, for example, the amino acid sequence shown in the SE * ID NO: in the SEC. ID NO: or the amino acid sequence encoded by the deposited cDNA clones can be determined conventionally using known computer programs such as the Bestfit Program (Wisconsin, Sequence Analysis, Version 8 for Unix, Genetics Computer Group, University Research Park, 575 Science Drive, Madison, Wl 53711). When the Bestfit or any other sequence alignment program is used to determine whether a particular sequence is, for example, 95% identical to a reference sequence according to the present invention, the parameters are set, - of course, of such that the percent identity is calculated over the entire length of the reference nucleotide sequence and that spaces or cleavage in homology of up to 5% of the total number of amino acid residues in the reference sequence are allowed.

A preferred method for determining the best total match between a reference sequence (a sequence of the present invention) and an objective sequence, also referred to as a global sequence alignment, can be determined using the FASTDB computer program based on the algorithm of Brutlag et al. C omp. App l. B i o s c i. 6: 2 3 1 - 2 4 5 (1990). In a sequence alignment, the reference and target sequences are both amino acid sequences. The result of said global sequence alignment is a percentage identity. The preferred parameters used in an FASTDB amino acid alignment are: Matrix = PAM 0, k-tuple = 2, Penalty for Non-Pairing = 1, Penalty for Union = 20, Group Length-for Randomization = 0, Court Record = 1, Penalty by Separation = 5, Penalty by Size of Separation = 0.05, Window Size = 500 or - the length of the target amino acid sequence, even if it is shorter.

If the target sequence is shorter than the reference sequence due to N- or C-terminal deletions, not due to internal deletions, a manual correction to the results must be made. This is because the FASTDB program does not count the N- and C-terminal truncations of the target sequence when calculating the global identity percentage. For the objective sequences truncated in the N- and C-1 erin 1 is, in relation to the reference sequence, the percentage of identity is corrected by calculating the number of residues of the reference sequence that are N- and C- terminals of the target sequence, which do not appear with a corresponding target residue, as a percentage of the total residues of the reference sequence. If it is determined that - - a nucleotide is ap- peared by the results of the alignments of the FASTDB sequence. This percentage is then subtracted from the identity percentage, calculated by the previous FASTDB program using the specified parameters, to arrive at a final percentage identity record. This final percentage identity record is what is used for the purpose of the present invention. Only the residues in the N- and C-terminals of referential sequence that do not appear in the sequence of reference, are considered for the purposes of manual adjustment -of the identity record of the percentage. That is, only the reference residue positions outside the N- and C-terminal residues furthest from the target sequence. And, for example, an objective sequence of 90 amino acid residues is aligned to a reference sequence of 100 amino acid residues to determine the percentage of 25 identity. Deletions occur at the - N-terminus of the target sequence and, therefore, the FASTDB alignment does not show a 1-neation of the first 10 residues at the N-terminus. The 10 unpaired residues represent 10% of the sequence (number of residues in the N- and C-terminals not matched s / total number of residues in the reference sequence) so that 10% is subtracted from the identity percentage record calculated by the FASTDB program. If the remaining 90 residues match perfectly the identity of the final percentage would be 90%. In another example, an objective sequence of 90 residues is compared to a reference sequence of 100 residues. This time, the deletions are internal, so there are no residues in the N- and C-terminals of the target sequence that are not appended to the reference. In this case, the identity percentage calculated by the FASTDB is not corrected manually. Again, only the positions of the residues outside the N- and C-terminal ends of the target-sequence, as shown in the FASTDB alignment that are not mapped s / a 1 s with the sequence of reference are corrected manually. No other manual correction is made for the purpose of the present invention.

The polypeptides of the present invention are useful as molecular weight markers on SDS-PAGE gels or on molecular sieve gel filton columns using methods well known to those skilled in the art.

In another aspect, the invention provides a peptide or polypeptide comprising a portion carrying an epitope of a polypeptide of the invention. The epitope of this portion of the polypeptide is an immunogenic or antigenic epitope of a polypeptide described herein. An "immunogenic epitope" is defined as a part of a protein that genes an antibody response when the entire protein is the immunogen. On the other hand, a region of the protein molecule to which an antibody can bind is defined as an "antigenic epitope". The number of immunogenic epitopes of a protein is generally less than the number of antigenic epitopes. See, for example, Geysen et al. , Proc. Natl. Acad. Sci. USA 81: 3998-4002 (1983).

Regarding the selection of antigenic epitope-bearing peptides or polypeptides, i.e., containing a region of a protein molecule to which an antibody can be linked), it is well known in the art that relatively short synthetic peptides that mimic part of a protein sequence are routinely capable of geneng an antiserum that reacts with the partially mimicked protein. See, for example, Sutcliffe, J. G. et al. , "Antibodies that react with predetermined sites on proteins", Science 219: 660-666 (1983). Peptides capable of geneng a serum reactive with the protein are frequently represented - in the primary sequence of a protein, they can be characterized by a set of simple chemical rules, and they are not confined to the immunodominant regions of the intact proteins ( that is, immunogenic epitopes) nor to the amino or carboxymethyl groups.

The peptides and polypeptides carrying the antigenic epitopes of the invention are therefore useful for geneng antibodies, including monoclonal antibodies, that specifically bind to a polypeptide of the invention. See, for example, Wilson et al. , Ce l l 3 7: 1 6 1 - 1 18 (1984) in 777.

The peptides and polypeptides carrying the antigenic epitopes of the invention preferably contain a sequence of at least seven, more preferably at least nine and more preferably between at least 15 to about 30 amino acids contained within the amino acid sequence of a polypeptide of the invention.

- The peptides and polypeptides carrying the epitopes of the invention can be produced by any conventional means. Houghten, R. A., "General method for the rapid solid-phase synthesis of large numbers of peptides: specificity of an ige n - an t ibody interaction at the level of individual amino acids", Proc. Natl. Acad. Sci. USA 82: 5131-5135 (1985). This "Simultaneous Multiple Peptide Synthesis (SMPS) Synthesis" process is further described in U.S. Patent No. 4, 631,111 to Houghten et al. (1986).

As one of ordinary skill in the art will appreciate, the METH1 or METH2 polypeptides of the present invention and epitope-bearing fragments thereof described above can be combined with portions of the constant domain of immunoglobulins (IgG), which result in polypeptides. chimeric These fusion proteins facilitate purification and show an increase in half-life in vivo. This has been shown, for example, for chimeric proteins consisting of the two rimp ^ domains of the human CD4 polypeptide and various domains of the heavy or light chain constant regions of mammalian immunoglobulins (EPA 394,827; Traunecker et al. , Nature 331: 84-86 (1988)). Fusion proteins that have a dimeric structure linked to the disulfide due to the IgG part may also be more efficient in binding and neutralizing other molecules than the monomeric METH1 and METH2 protein or fragments of the proteins alone (Fountoulakis et al., J. Biochem 270: 3958-3964 (1995)).

Polynucleotide and fragments of polypeptides METHl and METH2 In the present invention, a "polynucleotide fragment" refers to a short polynucleotide having a nucleic acid sequence contained in the clones deposited or shown in SEQ. ID NO: 1 or SEC. ID NO: 3. The short nucleotide fragments are preferably at least about 15 nt, and more preferably at least about 20 nt, still more preferably at least about 30 nt, and even more preferably at least about 40 nt in length. A fragment "of at least 20 nt in length", for example, is indicated to include 20 or more contiguous bases of the cDNA sequence contained in the deposited clones or the nucleotide sequence shown in SEQ. ID NO: 1 or in -the SEC. ID NO: 3. These nucleotide fragments are useful as useful as diagnostic probes and primers as discussed herein. Of course, larger fragments are preferred (eg, 50, 150, 500, 600, 2000 nucleotides).

In addition, representative examples of the polynucleotide fragments METH1 or METH2 include, for example, fragments having a sequence from about nucleotide numbers 1-50, 51-100, 101-150, 151-200, 201-250, 251 -300, 301-350, 351-400, 401-450, 451-500, 501-550, 551-600, 651-700, 701-750, 751-800, 800-850, 851-900, 901-950, 951-1000, 1001-1050, 1051-1100, 1101-1150, 1151-1200, 1201-1250, 1251-1300, 1301-1350, 1351-1400, 1401-1450, 1451-1500, 1501-1550, 1551-1600, 1601-1650, 1651-1700, 1701-1750, 1751-1800, 1801-1850, 1851-1900, 1901-1950, 1951-2000, or 2001 to the end of the SEC. ID NO: 1 or SEC. ID NO: or of the cDNA contained in the deposited clones. In this context "approximately" includes the ranges recited particularly, larger or smaller by several (5, 4, 3, 2 or 1) nucleotides, in either terminal or both terminals. Preferably, these fragments encode - a polypeptide having a biological activity. More preferably, these polynucleotides can be used as probes or primers as discussed herein.

In the present invention, a "polypeptide fragment" refers to a short amino acid sequence contained in SEQ. ID NO: 2 or in the SEC. ID NO: 4 or encoded by the cDNA contained in the deposited clones.

- -Fragments of proteins can be "free", or comprised within a larger polypeptide of which the fragment forms a part or region, more preferably as a single continuous region. Representative examples of the polypeptide fragments of the invention include, for example, fragments from about amino acid numbers 1-20, 21-40, 41-60, 61-80, 81-100, 102-120, 121-140, 141-160, 161-180, 181-200, 201-220, 221-240, 241-260, 261-280, or 281 to the end of the coding region or SEC. ID NO: 2 or the SEC. ID NO: 4. In addition, fragments of the polypeptide can be about 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130, 140, or 150 amino acids in length. In this context "approximately" includes the ranges recited particularly, larger or smaller by several (5, 4, 3, 2 or 1) amino acids, at either end or both ends.

Preferred polypeptide fragments include the METH1 or secreted METH2 protein - as well as the mature form. Additional preferred polypeptide fragments include the secreted METH1 or METH2 protein or the mature form having a continuous series of residues removed from the amino or carbo-terminal, or both. For example, any number of amino acids, ranging from 1-60, can be eliminated from amino-terminal or from any secreted METH1 or METH2 polypeptide or mature form. Similarly, any number of amino acids, ranging from 1-30, can be removed from the carboxy terminal of the secreted METH1 or METH2 protein or the mature form. In addition, any combination of the above-mentioned amino and carboxy terminal deletions is preferred. Similarly, polynucleotide fragments encoding these fragments of the METH1 or METH2 polypeptide are also preferred.

Particularly, the N-terminal deletions of the METH1 polypeptide can be described by the general formula m-950, where m is an integer from 2 to 949, where m corresponds to the position - of the amino acid residue identified in the SEC . ID NO: 2. Preferably, the N-terminal deletions of the METH1 polypeptide of the invention shown in SEQ. ID NO: 2 include the polypeptides comprising the amino acid sequence of the residues: G-2 to S-950; N-3 to S-950; A- 4 to S-950; E-5 to S-950; R-6 to S-950; A-7 to S-950; P-8 to S-950; G-9 to S-950; S-10 to S-950; R-ll to S-950; S-12 to S-950; F-13 to S-950; G -14 to S-950; P-15 to S-950; V- 16 to S-950; P-17 to S-950; T-18 to S-950; L-19 to S-950; L-20 to S-950; L-21 to S-950; L-22 to S-950; A-23 to S-950; A-24 to S-950; A-25 to S-950; L -26 to S-950; L-27 to S-950; A-28 to S-950; V-29 to S-950; S-30 to S-950; D-31 to S-950; A-32 to S-950; L-33 to S-950; G-34 to S-950; R-35 to S-950; P-36 to S-950; S-37 to S-950; E -38 to S-950; E-39 to S-950; D-40 to S-950; E-41 to S-950; E-42 to S-950; L-43 to S-950; V-44 to S-950; V-45 to S-950; P-46 to S-95Q; E-47 to S- - -950; L-48 to S-950; "E-49 to S-950; R -50 to S-950; A-51 to S-950; P-52 to S-950; G-53 to S-950; H -54 to S-950, G-55 'to S-950, T-56 to S-950, T-57 to S-950, R-58 to S-950, L-59 to S-950, R- 60 to S-950, L-61 to S-950, H-62 to S-950, A-63 to S-950, F-64 to S-950, D-65 to S-950, Q-66 to S-950; Q-67 up to S-950; L-68 up to S-950; D-69 up to S-950; L-70 to S-950, E-71 to S-950, L-72 to S-950, R-73 to S-950, P-74 to S-950, D-75 to S-950, S- 76 to S-950, S-77 to S-950, F-78 to S-950, L-79 to S-950, A-80 to S-950, P-81 to S-950, G-82 to S-950-, F-83 up to S-950, T-84 up to S-950, L-85 up to S-950, Q -86 up to S-950, N-87 up to S-950, V-88 up to S -950; G-89 to S-950; R-90 to S-950; K-91 to S-950; S-92 to S-950; G-93 to S-950; S-94 to S-950;; E-95 to S-950; T-96 to S-950; P-97 to S-950; L-98 to S-950; P-99 to S-950; E-100 to S-950; -101 to S-950, D-102 to S-950, Ll 03 to S-950, A-104 to S-950, Hl 05 to S-950, Cl 06 to S-950, F-107 to S- 950, Y-108 to S-950, S-109 to S-950, G-110 to S-950, T-III to S-950, V-112 to S-950, NL 13 to S-950, G -114 to S-950, D-115 to S-950, P-116 to S-950, S-117 to S-950, S-118 to S-950, A-119 to S-950, A-120 up to S-950, A-121 up to S-950, L-122 up to S-950, S-123 has ta S-950; L-124 to S-950; C-125 to S-950; E-126 to S-950; G-127 to S-950; V-128 to S-950; R-129 to S-950; G-130 to S-950; A-131 to S-950; F-132 to S-950; Y-133 to S-950; L-134 to S-950; L-135 to S-950; G-136 to S-950; E-137 to S-950; A-138 to S-950; And -139 to S-950; F-140 to S-950; 1-141 to S-950; Q-142 to S-950; P-143 to S-950; L-144 to S-950; P-145 to S-950; A-146 to S-950; A-147 to S-950; S-148 to S-950; E-149 to S-950; R-150 to S-950; L-151 to S-950; A-152 to S-950; T-153 to S-950; A-154 to S-950; A-155 to S-950; P-156 to S-950; G-157 to S-950; E-158 to S-950; K-159 to S-950; P-160 to S-950; P-161 to S-950; A-162 to S-950; P-163 to S-950; L-1 64 to S-950; Q-165 to S-950; F-166 to S-950; H-l 67 to S-950; L-168 nasta S-950; L-169 to S-950; R-170 to S-950; R-171 to S-950; N-172 up S-950; R-173 to S-950; Q-174 to S-950; G-175 to S-950; D-176 to S-950; V-177 to S-950; G-178 to S-950; G-179 up S-950; T-180 to S-950; C-181 to S-950; G-182 to S-950; V-183 to S-950; V-184 to S-950; D-185 to S-950; D-186 to S-950; E-187 to S-95Q; P-188 to S-950; R-189 to S-950; P-190 to S-950; T-191 to S-950; G-192 to S-950; K-193 up S-950; A-194 to S-950; E-195 to S-950; T-196 to S-950; E-197 to S-950; D-198 to S-950; E-199 to S-950; D-200 up S-950; E-201 to S-950; G-202 to S-950; T-203 to S-950; E-204 to S-950; G-205 to S-950; E-206 to S-950; D-207 up S-950; E-208 to S-950; G-209 to S-950; P-210 to S-950; Q-211 to S-950; W-212 to S-950; S-213 to S-950; P-214 up S-950; Q-215 to S-950; D-216 to S-950; P-217 to S-950; A-218 to S-950; L-219 to S-950; Q-220 up to S-950 G-221 up to S-950; V-222 to S-950; G-223 to S-950; - - Q-224 to S-950; P-225 to S-950; T-226 to S-950; G-227 to S-950; T-228 up S-950; G-229 to S-950; S-230 to S-950; 1-231 to S-950; R-232 to S-950; R-233 to S-950; K-234 to S-950; R-235 up S-950; F-236 to S-950; V-237 to S-950; S-238 to S-950; S-239 to S-950; H-240 to S-950; R-241 to S-950; Y-242 up S-950; V-243 to S-950; E-244 to S-950; T-245 to S-950; M-246 to S-950; L-247 to S-950; V-248 to S-950; A-249 up S-950; D-250 to S-950; Q-251 to S-950; S-252 to S-950; M-253 to S-950; A-254 to S-950; E-255 to S-950; F-256 to S-950; H-257 to S-950; G-258 to S-950; S-259 to S-950; G-260 to S-950; L-261 to S-950; K-262 to S-950; H-263 to S-950; Y-264 to S-950; L-265 to S-950; L-266 to S-950; T-267 to S-950; L-268 to S-950; F-269 to S-950; S-270 to S-950; V-271 to S-950; A-272 to S-950 A-273 to S-950; R-274 to S-950; L-275 to S-950; Y - 2 1 6 to S-950; K-277 to S-950; H-278 to S-950; P-279 to S-950; ? -280 to S-950; 1-281 to S-950; R-282 to S-950; N-283 to S-950; S-284 to S-950; V-285 to S-950; S-286 to S-950; L-287 to S-950; V-288 to S-950; V-289 to S-950; V-290 to S-950; K-291 to S-950; 1-292 to S-950; L-293 to S-950; V-294 to S-950; 1-295 to S-950; H-296 to S-950; D-297 to S-950; E-198 to S-950; Q-299 to S-950; K-300 up to S-950; G-301 to S-950; P-302 to S-950; E-303 to S-950; V-304 to S-950; T-305 to S-950; S-306 to S-950; N-307 to S-950; A-308 to S-950; A-309 to S-950; L-310 to S-950; T-311 to S-950; L-312 to S-950; R-313 to S-950; N-314 to S-950; F-315 to S-950; C-316 to S-950; N-317 to S-950; W-318 to S-950; Q-319 to S-950; K-320 to S-950; Q-321 to S-950; H-322 to S-950; N-323 to S-950; P-324 to S-950; P-325 up to S-950 S-326 up to S-950; D-327 to S-950; R-328 to S-950; D-329 to S-950; A-330 to S-950; E-331 to S-950; H-332 to S-950; And -333 to S-950; D-334 to S-950; T-335 to S-950; A-336 to S-950; 1-337 to S-950; L-338 to S-950; F-339 to S-950; T-340 to S-950; R-341 to S-950; Q-342 to S-950; D-343 to S-950; L-J44 to S-950; C-345 to S-950; G-346 to S-950; S-347 up S-950; Q-348 to S-950; T-349"up to S-950; C-350 up to S-950; D-351 to S-950; T-352 to S-950; L-353 to S-950; G-354"up S-950; M-355 to S-950; A- 356 to S-950; D-357 to S-950; V-358 to S-950; G-359 to S-950; T-360 to S-950; V-361 to S-950; C-362 to S-950; D-363 to S-950; P-364 to S-950; S-365 to S-950; R-366 to S-950; S-367 to S-950; C-368 up S-950; S-369 to S-950; V-370 to S-950; 1-371 to S-950; E-372 to S-950; D-373 to S-950; D-374 to S-950; G-375 up S-950; L-376 to S-950; Q-377 to S-950; A-378 to S-950; A-379 to S-950; F-380 to S-950; T-381 to S-950; T-382 up S-950; A-383 to S-950; H-384 to S-950; E-385 to S-950; L-386 to S-950; G-387 to S-950; H-388 to S-950; V-389 up S-950; F-390 to S-950; N-391 to S-950; M-392 to S-950; P-393 to S-950; H-394 to S-950; D-395 to S-950; D-396 to S-950; A-397 to S-950; K-398 to S-950; - - Q-399 to S-950; C-4 'O O to S-950; A-401 to S-950; S-402 to S-950; L-403 up S-950; N-404 to S-950; G-405 to S-950; V-406 to S-950; N-407 to S-950; Q-408 to S-950; D-409 to S-950; S-410 up S-950; H-411 to S-950; M-412 to S-950; M-413 to S-950; A-414 to S-950; S-415 to S-950; M-416 to S-950; L-417 up S-950; S-418 to S-950; N-419 to S-950; L-420 to S-950; D-421 to S-950; H-422 to S-950; S-423 to S-950; Q-424 up S-950; P-425 to S-950; W-426 to S-950; S-427 to S-950; P-428 to S-950; C-429 to S-950; S-430 to S-950; A-431 to S-950; Y-432 to S-950; M-433 to S-950; 1-434 to S-950; T-435 to S-950; S-436 to S-950; F-437 to S-950; L-438 up S-950; D-439 to S-950; N-440 to S-950; G-441 to S-950; H-442 to S-950; G-443 to S-950; E-444 to S-950; C-445 up S1950; L-446 to S-950; M-447 to S-950; D-448 to S-950; K-449 to S-950; P-450 to S-950; Q-451 to S-950; N - 452 ~ up S-950; P-453 to S-950; 1-454 to S-950; Q-455 to S-950; L-456 to S-950; P-457 - -up to S-950; G-458 to S-950; D-459 hast-a S-950; L-460 to S-950; P-461 to S-950; G-462 to S-950; T-463 to S-950; S-464 to S-950; Y-465 to S-950; D-466 up S-950; A-467 to S-950; N-468 to S-950; R-469 to S-950; Q-470 to S-950; C-471 to S-950; Q-472 to S-950; F-473 up S-950; T-474 to S-950; F-475 to S-950; G-476 to S-950; E-477 to S-950; D-478 to S-950; S-479 to S-950; K-4 &0 up S-950; H-481 to S-950; C-482 to S-950; P-483 to S-950; D-484 to S-950; A-485 to S-950; A- 486 to S-950; S-487 up S-950; T-488 to S-950; C-489 to S-950; S-490 to S-950; T-491 to S-950; L-492 to S-950; W-493 to S-950; C-494 up S-950; T-495 to S-950; G-496 to S-950; T-497 to S-950; S-498 to S-950; G-499 to S-950; G-500 to S-950; V - 501 up S-950; L-502 to S-950; V-503 to S-950; C-504 to S-950; Q-505 to S-950; T-506 to S-950; K-507 to S-950; H-508 up S-950; F-509 to S-950; P-510 to S-950; W-511 S-950; A-512 to S-950; D-513 up S-950; G-514 to S-950; T-515 to S-950; - - S-516 to S-950; C-517 to S-950; G-518 to S-950; E-519 to S-950; D-520 up S-950; K-521 to S-950; W-522 to S-950; C-523 to S-950; 1-524 to S-950; N-525 to S-950; G-526 to S-950; K-527 up S-950; C-528 to S-950; V-529 to S-950; N-530 to S-950; K-531 to S-950; T-532 to S-950; D-533 to S-950; R-534 up S-950; K-535 to S-950; H-536 to S-950; F-537 to S-950; D-538 to S-950; T-539 to S-950; P-540 to S-950; F-541 up S-950; H-542 to S-950; G-543 to S-950; S-544 to S-950; W-545 to S-950; G-546 to S-950; M-547 to S-950; W-548 to S-950 G-5-49 to S-950; P-550 to S-950; W-551 to S-950; G-552 to S-95Q; D-553 to S-950; C-554 to S-950; S-555 up S-950; R-556 to S-950; T-557 to S-950; C-558 to S-950; G-559 to S-950; G-560 to S-950; G-561 to S-950; V-562 up S-950; Q-563 to S-950; Y-564 to S-950; T-565 to S-950; M-566 to S-950; R-567 to S-950; E-568 to S-950; C-569 up S-950; D-570 to S-950; N-571 to S-950; P-572 to S-950; V-573 to S-950; P-574 - -up to S-950; K-575 to S-950; N-576 up S-9-50; G-577 to S-950; G-578 to "S-950; K-579 to S-950; Y-580 to S-950; C-581 to S-950; E-582 to S-950; G-583 to S-950; K-584 to S-950; R-585 to S-950; V-586 antler R-587 re S-950 Y-588 up to S-950 R- 589 has S-950 S-590 up S-950; C-591 to S-950; N-592 antler S-950; L-593 to S-950; E-594 to S-950; D-595 to S-950; C-596 antler S-950; P-597 up S-950; D-598 to S-950; N-599 antler S-950; N-600 to S-950; G-601 to S-950; K-602 to S-950; T-603 to S-950; F-604 up S-950; R-605 to S-950; E-606 to S-950; E-607 to S-950; Q-608 to S-950; C-609 to S-950; E-610 to S-950; A- 611 up S-950; H-612 to S-950; N-613 antler S-950; E-614 to S-950; F-615 to S-950; S-616 to S-950; K-617 to S-950; A-618 up S-950; S-619 to S-950; F-620 to S-950; G - 621 to S-950; S-622 to S-950; G-623 to S-950; ' P-624 to S-950; A- 625 up S-950; V-626 antler S-950; E-627 to S-950; W-628 to S-950; 1-629 to S-950; P-630 to S-950; K-631 to S-950; Y-632 to S-950; A- 633 to S-950; G-634 to S-950; V-635 to S-950; S-636 to S-950; P-63 ^ to S-950; K-638 to S-950; D-639 up S-950; R-640 to S-950; C-641 to S-950; K-642 to S-950; L-643 to S-950; 1-644 to S-950; C-645 to S-950; Q-646 up S-950; A-647 to S-950; K-648 to S-950; G-649 to S-950; 1-650 to S-950; G-651 to S-950; Y-652 to S-950; F-653 nasta S-950; F-654 nasta S-950; V-655 to S-950; L-656 to S-950; Q-657 to S-950; P-658 to S-950; K-659 to S-950; V-660 up S-950; V- 661 to S-950; D-662 to S-950; G-663 to S-950; T-664 to S-950; P-665 to S-950; C-666 to S-950; S-667 up S-950; P-668 to S-950; D-669 to S-950; S-670 to S-950; T-671 to S-950; S-672 to S-950; V-673 to S-950; C-674 up S-950; V-675 to S-950; Q-676 to S-950; G-677 to S-950; Q-67S to S-950; C-679 to S-950; V-680 to S-950; K-681 up S-950; A-682 to S-950; G-683 to S-950; C-684 to S-950; D-685 to S-950; R-686 to S-950; 1-687 to S-950; 1-688 to S-950; D-689 to S-950; S-690 to S-950; K-691 to S-950; K-692 to S-950; K-693 to S-950; F-694 to S-950; D-695 up S-950; K-696 to S-950; C-697 to S-950; G-698 to S-950; 'V-699 to S-950; C-700 to S-950; G-701 to S-950; G-702 up S-950; N-703 to S-950; G-704 to S-950; S-705 to S-950; T-706 to S-950; C - "? 07 up to S-950; K-708 up to S-950; K-709 up S-950; 1-710 to S-950; S-711 to S-950; G-712 to S-950; S-713 to S-950; V-714 to S-950; T-715 to S-950; S-716 up S-950 A - l 1 1 up to S-950 K-718 up to S-950 P-719 to S-950; G-720 to S-950; Y-721 to S-950; H-722 to S-950; D-723 up S-950; 1-724 to S-950; 1-725"up to S-950; T-726 to S-950; 1-727 to S-950 P-728 to S-950; T-729 to S-950; G-730 up S-950; A-731 to S-950; T-732 to S-950; N-733 to S-950; 1-734 to S-950; E-735 to S-950; V-736 to S-950; K-737 up S-950; Q-738 to S-950; R-739 to S-950; N-740 to S-950; Q - 741 to S-950; "R-742 up to S-950; G-743 up to S-950; S-744 up S-950; R-745 to S-950; N-746 to S-950; N-747 to S-950; G-748 to S-950; S-749 - -up to S-950; F-750 to S-950; L-751 up S-950; A-752 to S-950; 1-753 to S-950; K-754 to S-950; A- 755 to S-950; A- 756 to S-950; D-757 to S-950; G-758 to S-950; T-759 to S-950; Y-760 to S-950; 1-761 to S-950; L-762 to S-950; N-763 antler S-950; G-764 to S-950; D-765 up S-950; Y -766 antler S-950; T-767 to S-50; L-768 to S-950; S-769 to S-950; T-770 to S-950; L-771 to S-950; E-772 up S-950; Q-773 to S-950; D-774 to S-950; 1-775 to S-950; M-776 to S-950; Y - 1 1 1 to S-950; K-778 to S-950; G-779 up S-950; V-780 to S-950; V-781 to S-950; L-78Z to S-950; R-783 to S-950; Y-784 to S-950; S-785 to S-950; D-786 up S-950; S-787 to S-950; S-788 to S-950; A-789 to S-950; A-790 to S-950; L-791 to S-950; E-792 to S-950; R-793 to S-950; 1-794 to S-950; R-795 to S-950; S-796 to S-950; F-797 to S-950; S-798 to S-950; P-799 to S-950; L-800 up S-950; K-801 to S-950; E-802 to S-950; P-803 to S-950; L-804 to S-950; T-805 to S-950; 1-806 to S-950; Q-807 to-S-950; V-808 to S-950; V-809 to S-950; T-810 to S-950; V-811 to S-950; G-812 to S-950; N-813 to S-950; A- 814 up S-950; L-815 to S-950; R-816 to S-950; P-817 to S-950; K-818 to S-950; 1-819 to S-950; - 820 to S-950; And -821 up S-950; T-822 to S-950; And -823 to S-950; F-824 to S-950; V-825 to S-950; K-826 to S-950; K-827 to S-950; K-828 up S-950; K-829 to S-950; E-830 antler S-950; S-831 antler S-950; F-332 to S-950; N-833 to S-950; A- 834 to S-950; 1-835 up S-950; P-836 to S-950; T-537 to S-950; F-838 to S-950; S-839 to S-950; A-840 to S-950; W-841 to S-950; V-842 up S-950; 1-843 to S-950; E-844 to S-950; E-845 to S-950; W-846 to S-950; G-847 to S-950; E-848 to S-950; C-849 up S-950; S-850 to S-950; K-851 to S-950; S-852 to S-950; C-853 to S-950; E-854 to S-950; L-855 to S-950; G-856 up S-950; W-857 to S-950; Q-858 to S-950; R-859 to S-950; R-860 to S-950; L-861 to S-950; V-862 to S-950; E-863 up S-950; C-864 to S-950; R-865 to S-950; D-866 to S-950; 1-867 to S-950; N-868 to S-950; G-869 to S-950; Q-870 up S-950; P-871 to S-950; A-872 to S-950; S-873 to S-950; E-874 to S-950; C-875 antler S-950; A-876 to S-950; K-877 up S-950; E-878 to S-950; V-879 to S-950; K-880 to S-950; P-881 to S-950; A-882 antler S-950; S-883 to S-950; T-8S4 up S-950; R-885 to S-950; P-886 to S-950; C-887 to S-950; A-888 to S-950; D-8S9 antler S-950; H-890 to S-950; P-891 up S-950; C-892 to S-950; P-893 to S-950; Q-894 to S-950; W-895 to S-950; Q-896 to S-950; L-897 to S-950; G-898 to S-950; E-899 to S-950; W-900 up to S-950; S-901 to S-950; S-902 to S-950; C-903 to S-950; S-904 to S-950; K-905 up S-950; T-906 to S-950; C-907 to S-950; G-908 to S-950 .; K-909 to S-950; G-910 to S-950; Y- 911 to S-950; K-912 up S-950; K-913 to S-950; R-914 to S-950; S-915 to S-950; L-916 to S-950; K-917 to S-950; C-918 to S-950; L-919 up S-950; S-920 to S-950; H-921 to S-950; D-922 to S-950; G-923 to S-950; G-924 - -up to S-950; V-925 to S-950; L-926 to S-950; S-927 to S-950; H-928 to S-950; E-929- to S-950; S-930 to S-950; C-931 to S-950; D-932 to S-950; P-933 to S-950; L-934 to S-950; K-935 to S-950; K-936 to S-950; P-937 to S-950; K-938 to S-950; H-939 to S-950; F-940 to S-950; 1-941 to S-950; D-942 to S-950; F-943 to S-950; C-944 to S-950; T-945 to S-950; of the SEC. ID NO. 2.

In addition, C-terminal deletions of the METH1 polypeptide can also be described by the general formula 1-n, where n is an integer from 2 to 950, where "n corresponds to the position of 1 amino acid residue identified in the SEQ ID NO 2. Preferably, the C-terminal deletions of the METH1 polypeptide of the invention show how SEQ ID No. 2 includes the polypeptides comprising the amino acid sequence of the residues: M-1 through C-949 Ml to E-948, Ml to A-947, Ml to M-946, Ml to T-945, Ml to -944, Ml to F-943, M1 to D942, Ml to 1-941, Ml to F-940, Ml to H-939, Ml to K-938, Ml to P -937, Ml to K-936, Ml to K-935, Ml to L-934, Ml to P- 933; Ml up to D-932; Ml up to C-931; Ml up to S-930; Ml up to E-929; Ml up to H-928; Ml up to S-927; Ml up to L-926; Ml up to V-925; Ml to G-924, Ml to G-923, Ml to D -922, Ml to H-921, Ml to antler S-920; M-l up to L-919; M-l to C-918; M-1 to K-917; M-l up to L-916; M-1 to S-915; M -1 to R-914; M-1 to K-913; M-1 to K-912; M-l through Y-911; M-l to G-910; M-l to K-909; M-l to G-908; M-l to C-907; M-l up to T-906; M-l to K-905; M-1 to S-904; M-1 to C-903; M-1 to S-902; M-1 to S-901; M-l to W-900; M-l to E-899; M-l to G-898; M-l to L -897; M-l to Q-896; M-l through W-895; M-1 to Q-894; M-1 to P-893; M-1 to C -892; M-1 to P-891; M-1 to H-890; M-1 to D-889; M-1 to A-888; M-1 through C-887; M-1 to P-886; M-1 to R-885; M-l up to T-884; M-1 to S-883; M-1 to A- -882; M-1 to P-881; M-l up to K-880; M-1 to V-879; M-1 to E-878; M-l up to K-877; M-1 to A-876; M-1 to C-875; M-l to E-874; M-1 to S-873; M-1 to A-872; M-1 to P-871; M-l to Q-870; M-l to G-869; M-1 to N-868; M-1 to I-867; M-1 to D-866; M-1 to R-865; M-1 to C-864; M-1 to E-863; M-1 to V-862; M-1 to L-861; M-1 to R-860; M-1 to R-859; M-1 to Q-858; M-l through W-857; M-1 to G-856; M-1 to L-855; M-1 to E-854; M-1 to C-853; M-1 to S -852; M-1 to K-851; M-1 to S-850; M-l through C-849; M-l to E-848; M-1 to G-847; M-l through W-846; M-1 to E-845; M-1 to E-844; M-1 to 1-843; M-1 to V-842; M-l to W-841; M-1 to A-840; M-1 to S-839; 'M-l up to F-838; M-l to T -837; M-1 to P-836; M-1 to 1-835; M-1 to A-834; M-1 to N-833; M-1 through F-832; M-1 to S-831; M-l up to E-830; M-l to K-829; M-1 to K-828; M-1 to K-827; M-l through K-826; M-1 to V-825; M-l through F-824; M-1 through Y-823; M-1 to T-822; M-1 to Y-821; M-1 to K-820; M-1 - - up to 1-819; M-l to K-818; M-1 to P-817; M-1 to R-816; M-1 to L-815; M-1 through A-814; M-1 to N-813; M-1 to G-812; M-1 to V-811; M-l through T-810; M-l nasta L-809; M-1 to V-808; M-1 to O-807; M-1 to 1-806; M-l through T-8Q5; M-1 to L-804; M-1 to P-803; M-1 to E-802; M-1 to K-801; M-l through L-8Q0; M-1 to P-799; M-1 to S-798; M-1 to F-797; M-1 to S-796; M-1 to R-795; M-1, 1-794; M-1 to R-793; M-1 to E-792; M-1 to L-791; M-1 to A-790; M-1 through A-789; M-1 to S-788; M-1 to S-787; M-l to G-786; M-1 to S-785; M-1 to Y-784; M-1 to R-783; M-1 to L-782; M-1 to V-781; M-1 to V-780; M-l to G-779; M-l to K-778; M-l to Y -777; M-1 to M-776; M-1 to 1-775; M-1 to D-774; M-1 to Q-773; M-l to E -772; M-l to L-771; M-1 to 1-770; M-1 to S-769; M-i up to L-768; M-l up to T-767; M-1 to Y-766; M-1 to D-765; M-1 to G-764; M-1 to N-763; M-1 to L-762; M-1 to 1-761; M-1 to Y-760; M-l up to T-759; M-l up to G-758; M-1 to D- - - 757; M-1 to A-756; M-1 to A-755; M-l to K-754; M-1 to 1-753; M-1 to A-752; M-1 to L-751; M-1 to F-750; M-1 to S-749; M-1 to G-748; M-l to N -747; M-1 to N-746; M-1 to R-745; M-1 to S-744; M-1 to G-743; M-1 to R -742; M-l to Q-741; M-1 to N-740; M-1 to R-739; M-1 to Q-738; M-l to K -737; M-1 to V-736; M-l to E-735; M-1 to 1-734; M-1 to N-733; M-1 to T-732; M-1 to A-731; M-l to G-730; M-l hast-a T-729; M-1 to P-728; M-1 through I -727; M-l up to T-726; M-1 to 1-725; M-1 to 1-724; M-1 to D-723; M-1 to H-722; M-1 to Y-721; M-l to G-720; M-1 to P-719; M-1 to K-718; M-1 through A-717; M-1 to S-716; M-l up to T-715; M-1 through V-714; M • 1 to S-713; M-1 to G-712; M-1 to S-711; M-1 to 1-710; M-1 to K-709; M-1 to K-708; M-1 to C-707; M-1 to T-706; M-1 to S-705; M-1 to G-704; M - i to N-703; M-1 to G-702; M-l to G-701; M-l up to C-700; M-l through V-699; M-1 to G-698; M-l to C -697; M-l to K-696; M-1 to D-695; M-l - -up to F-694; M-1 to K-693; M-1 to K-692; M-l to K-691; M-1 to S-690; M-1 to D-689; M-1 to 1-688; M-1 through I -687; M-1 to R-686; M-l up to D-685; M-1 to C-684; M-1 to G-683; M-1 to A-682; M-1 to K-681; M-1 to V-680; M-l through C-679; M-l to Q-678; M-l to Q -677; M-l to Q-676; M-1 to V-675; M-1 through C-674; M-1 to V-673; M-1 to S-672; M-l up to T-671; M-1 to S-670; M-1 to D-669; M-l to P-668; M-1 to S-667; M-1 to C-666; M-1 to P-665; M-l up to T-664; M-1 to G-663; M-1 to D-662; M-1 to V-661; M-1 to V-660; M-l to K-659; M-1 to P-658; M-l to Q -657; M-1 to L-656; M-1 to V-655; M-l through F-654; M-1 to F-653; M-1 to Y -652; M-1 to G-651; M-1 to 1-650; M-l to G-649; M-l through K-648; M-l through A-647; M-l up to Q-646; M-1 to C-645; M-1 to 1-644; M-1 to L-643; M-l to K -642; M-1 to C-641; M-1 to R-640; M-1 to D-639; M-l up to K-638; M-1 to P -637; M-1 to S-636; M-1 to V-635; M-1 to G-634; M-1 to A-633; M-1 to Y- - 632; M-l up to K-631; M-1 to P-630; M-1 to 1-629; M-l through W-628; M-1 to E -627; M-1 to V-626; M-1 to A-625; M-1 to P-624; M-1 to G-623; M-1 to S-622; M-1 to G-621; M-1 to F-620; M-1 to S-619; M-1 to A-618; M-l through K-617; M-1 to S-616; M-1 through F-615; M-1 to E-614; M-1 to N-613; M-1 to H -612; M-1 through A-611; M-l to E-610; M-1 to C-609; M-1 through Q-608; M-1 to E -607; M-1 to E-606; M-1 to R-605; M-1 to F-604; M-l through T-603; M-1 to K-602; M-1 to G-601; M-1 to N-600; M-1 to N-599; M-1 to D-598; M-1 to P-597; M-1 to C-596; M-1 to D-595; M-1 to E-594; M-1 through L-593; M-1 to N-592; M-1 through C-591; M-1 to S-590; M-1 to R-589; M-i through Y-588; M-1 to R-587; M-1 to V-586; M-1 to R-585; M-l to K-584; M-l to G-583; M-1 to E-582; M-1 to C-581; M-l to Y-580; M-1 to K-579; M-1 to K-578; M-1 to G-577; M-1 to N-576; M-1 to K-575; M-1 to P-574; M-1 to V-573; M-1 to P -572; M-1 to N-571; M-l to D-570; M-l - up to C-569; M-1 to E-568; M-1 to R-567; M-1 to M-566; M-i up to T-565; M-1 through Y-564; M-1 through Q-563; M-i to V- 562; M-1 to G-561; M-l to G-560; M-l to G-559; M-1 to C-558; M-1 to T-557; M-1 to R-556; M-1 to S-555; M-1 to C-554; M-1 to D-553; M-1 to G-552; M-l through W-551; M-1 to P-550; M-l up to G-549 M -1 up to W-54 M-l up to M-547 M-l up to G-546 M-1 up to W-545 M-l up to S-544; M-l up to G-543 M-l up to H 542; M-1 through F-541; M-1 to P-54CL; M-l up to T-539; M 1 to D-538; M-1 through F-537; M-i to H-536; M-1 to K-535; M-1 to R-534; M 1 to D-533; M-1 through T-532; M-1 to K-531; M-1 to N-530; M-1 to V-529; M-1 to C-528; M-1 to K-527; M-l antler G-526; M-1 to N-525; M-1 to 1-524; M-1 to C-523; M-1 to W-522; M-i up to K-521; M-l through G-52Q; M-l through E-519; M-1 to G-518; M-1 to C-517; M-1 to S-516; M-l up to T-515; M-1 to G-514; M-1 to D-513; M-1 through A-512; M-l to W-511; M-1 to P-510; M-l through F-509; M-1 to H-508; M-1 to K- -507; M-l up to T-506; M-1 through Q-505; M-1 to C-504; M-1 to V-503; M-1 to L-502; M-1 to V-501; M-l up to G-500; M-1 to G-499; M-1 to S-498; M-1 to T-497; M-1 to G-496; M-1 through T-495; M-1 to C-494; M-l through W-493; M-l to L -492; M-1 to 1-491; M-1 to S-490; M-l to C-489 M-l to T-4 M-l to 7; M-1 to A-486; M-1 to A-485; M-1 to D-484 M-1 to P-483; M-l to C • 482; M-i to H -481; M-l up to K-480; M-1 to S-479; M-1 to D-478; M-1 to E -477; M-1 to G-476; M-1 to F-475; M-l through T-474; M-1 to F-473; M-l to Q -4 1 2; ' M-1 to C-471; M-l to Q-470; M-1 to R-469; M-1 to N-468; M-1 to A-467; M-1 to D-466; M-1 to Y-465; M-1 to S-464; M-1 through T-463; M-1 to G -462; M-1 to P 461; M-1 to L-460; M-1 to D-459; M-1 to G-458; M-l to P -457; M-l to L • 456; M-1 to Q-455; M-1 to 1-454; M-1 to P-453; M-1 to N -452; M-1 to Q-451; M-1 to P-450; M-l to K-449; M-1 to D-448; M-1 to M-447; M-1 to L-446; M-1 to C-445; M-l - up to E-444; M-1 to G-443; M-1 to H -442; M-1 to G-441; M-1 to N-440; M-1 to D-439; M-1 to L-438; M-1 to F -437; M-1 to S-436; M-l up to T-435; M-1 to 1-434; M-1 to M-433; M-l to Y -432; M-1 to A-431; M-1 to S-430; M-1 to C-429; M-1 to P-428; M-1 to S -427; M-l to W-426; M-1 to P-425; M-1 through Q-424; M-1 to S-423; M-1 to H -422; M-1 to D-421; M-l to L-420; M-1 to N-419; M-1 to S-418; M-1 to L-417; M-1 to M-416; M-1 to S-415; M-1 through A-414; M-1 to M-413; M-1 to M -412; M-1 to H-411; M-1 to S-410; M-1 to D-409; M-1 to Q-408; M-1 to N-407; M-1 to V -406; M-l to G-405; M-1 to N-404; M-1 to L-403; M-1 to S-402; M-1 to A-401; M-1 to C-400; M-l to Q-399; M-1 to K-398; M-1 to A-397; M-1 to D- -396; M-1 to D-395; M-1 to H-394; M-1 to P-393; M-l to M -392; M-1 to N - • 391; M-1 to F-390; M-1 to V-389; M-1 through H-388; M-1 to G-387; M-1 to L - • 386; M-l through E-385; M-1 to H-384; M-1 to A-383; M-1 to T- - -382; M-l through T-381; M-l up to F-380; M-l through A-379; M-1 to A-378; M-1 to Q-377; M-1 to L-376; M-1 to G-375; M-1 to D-374; M-1 to D-373; M-1 to E -372; M-1 to 1-371; M-1 to V-370; M-1 to S-369; M-1 to C-368; M-1 to S-367; M-1 to R-366; M-1 to S-365; M-1 to P-364; M-1 to D-363; M-1 to C-362; M-1 to V-361; M-l up to T-36-0; M-1 to G-359; M-1 to V-358; M-1 to D-357; M-1 to A-356; M-1 to M-355; M-l has a G-354; M-1 to L-353; M-1 to T-352; M-1 to D-351; M-1 to C-350; M-l through T-349; M-l through Q-348; M-1 to S-347; M-1 to G-346; M-1 to C-345; M-1 to L-344; M-1 to D-343; M-1 to Q-342; M-1 to R-341; M-l up to T-340; M-1 to F-339; M-1 to L-338; M-1 through I -337; M-1 to A-336; M-l up to T-335; M-1 to D-334; M-1 to Y-333; M-1 to H-332; M-1 to E-331; M-1 to A-330; M-1 to D-329; M-1 to R-328; M-1 to D-327; M-1 to S-326; M-1 to P-325; M-1 to P-324; M-l to 'N-323; M-1 to H -322; M-1 to Q-321; M-l up to K-320; M-l - -up to Q-319; M-l through W-318; M-1 to N -317; M-1 to C-316; M-l through F-315; M-1 to N-314; M-1 to R-313; M-l up to L - 312; M-l through T-311; M-1 to L-310; M-1 to A-309; M-1 to A-308; M-1 to N-307; M-1 to S-306; M-i up to T-305; M-1 to V-304; M-1 to E-303; M-1 to P -302; M-1 to G-301; M-l up to K-300; M-1 through Q-299; M-1 to E-298; M-1 to D-297; M-1 to H-296; M-1 to 1-295; M-1 to V-294; M-1 to L-293; M-1 through I -292; M-1 to K-291; M-1 to V-290; M-1 to V-289; M-1 through V-288; M-1 to L -287; M-1 to S-286; M-1 to V-285; M-1 to S-284; M-1 to N-283; M-1 to R -282; M-1 to 1-281; M-1 to S-280; M-1 to P-279; M-1 to H-278; M-l through K-277; M-1 to Y-276; M-1 to L-275; M-1 to R-274; M-1 through A-273; M-1 through A-272; M-1 through V-271; M-1 to S-270; M-1 through F-269; M-1 to L-268; M-1 to T-267; M-1 to L-266; M-1 to L-265; M-1 through Y-264; M-1 to H-263; M-1 to K -262; M-1 through L-261; M-1 to G-260; M-1 to S-259; M-1 to G-258; M-1 to H- - -257; M-1 to F-256; M-l to E-255; M-1 to A-254; M-1 to M-253; M-1 to S-252; M-i to Q-251; M-1 to D-250; M-1 to A-249; M-1 through V-248; M-1 to L-247; M-1 to M-246; M-l up to T-245; M-1 to E-244; M-1 to V-243; M-1 to Y-242; M-1 to R-241; M-1 to H-240; M-1 to S-239; M-1 to S-238; M-1 to V-237; M-1 through F-236; M-1 to R-235; M-l through K-234; M-1 through K-233; M-1 to R -232; M-1 to 1-231; M-1 to S-230; M-1 to G-229; M-1 to T-228; M-1 to G-227; M-1 to T-226; M-1 to P-225; M-1 through Q-224; M-1 to G-223; M-1 to V -222; M-1 to G-221; M-l up to Q-220; M-l to L-219; M-l through A-218; M-1 to P -217; M-1 to D-216; M-1 to Q-215; M-1 to P-214; M-1 to S-213; M-l through W -212; M-1 to Q-211; M-1 to P-210; M-1 to G-209; M-1 to E-208; M-1 to D -207; M-1 to E-206; M-1 to G-205; M-1 to E-204; M-l through T-203; M-1 to G-202; M-l to E-201; M-1 to D-200; M-l through E-199; M-1 to D-198; M-1 to E -197; M-1 through T-196; M-l through E-195; M-1 - up to A-194; M-1 to K-l 93; -M-l to G-192; M-1 through T-191; M-1 to P-190; M-l hast R-189; M-1 to P-188; M-l to E -187; M-1 to D-186; M-1 to D-185; M-1 to V-184; M-1 to V-183; M-1 to G-182; M-1 to C-181; M-l up to T-180; M-1 to G-179; M-l to G-178; M-1 to V -177; M-1 to D-176; M-1 to G-175; M-1 to Q-174; M-1 to R-173; M-1 to N -172; M-1 to R-171; M-1 to R-170; M-1 to L-169; M-1 to L-168; M-l to H -167; M-l antler F-166; M-1 to Q-165; M-1 to L-164; M-1 to P-163; M-1 to A-162; M-1 to P-161; M-1 to P-160; M-l Asta K-159; M - 1 to E-158; M-1 to G-157; M-1 to P-156; M-1 to A-155; M-1 to A-154; M-1 to T-153; M-1 to A-152; M-1 to L-151; M-1 to R-150; M-l through E-149; M - 1 to S-148; M-l through A-147; M-i to A-146; M-1 to P-145; M-l to L-144; M-1 to P-143; M-1 to Q -142; M-1 through 1-141; M-1 to F-140; M-1 to Y-139; M-1 to A-135; M-1 to E -137; M-1 to G-136; M-1 to L-135; M-1 to L-134; M-1 to Y-133; M-1 to F- - -132; M-1 to A-131; M-1 to G-130; M-1 to R-129; M-1 to V-128; M-l to G-127; M-l to E-126; M-1 to C-125; M-1 to L-124; M-1 to S-123; M-l to L -122; M-1 to A-121; M-1 to A-120; M-1 through A-119; M-1 to S-118; M-1 to S-117; M-1 to P-116; M-1 to D-115; M-1 to G-114; M-1 to N-113; M-1 to V -112; M-l through T-III; M-l up to G-11 ü; M-1 to S-109; M-1 to Y-108; M-l through F -107; M-1 to C-106; M-1 to H-105; M-I to A-104; M-1 to L-103; M-1 to D -102; M-1 through T-101; M-l up to E-100; M-1 to P-99; M-l through L-98; M-1 to P-97; M-l up to T-96; M-l to E-95; M-1 to S-94; M-1 to G-93; M-1 to S-92_; M-l to K-91; M-1 to R-90; M-l to G-89; M-1 to V-88; M-1 to N-87; M-l to Q -86; M-l up to L-85; M-l up to T-84; M-l through F-83; M-1 to G-82; M-l up to "p-81; M-l up to A-80; M-l through L-79; M-1 to F-78; M-1 to S-77; M-1 to S-76; M-1 to D-75; M-l to P-74; M-1 to R-73; M-l to L-72; M-l through E-71; M-1 to L-70; M-1 through D-69; M-l to L-68; M-l - -up to Q-67; M-l to Q-66; M-l to D-65, M-l through F-64; M-i to A-63; M-1 to H-62; M-1 to L-61; M-1 to R-60; M-l to L-59; M-l to G-58; M-l up to T-57; M-l up to T-56; M-l up to G-55; M-1 to H-54; M-l up to G-53; M-1 to P-52; M-1 to A-51; M-1 to R-50; M-l through E-49; M-l through L-48; M-l to E-47; M-1 to P-46; M-1 to V-45; M-1 to V-44; M-l to L-43; 'M-l to E-42; M-l to E-41; M-1 to D-40; M-l to E-39; M-1 to E-38; M-1 to S-37; M-1 to P-36; M-1 to R-35; M-l to G-34; M-l to L-33; M-l through A-32; M-1 to D-31; M-1 to S-30; M-1 to V-29; M-l through A-28; M-l up to L-27; M-l to L-26; M-1 to A-25; M-l through A-24; M-1 to A-23; M-1 to L-22; M-1 to L-21; M-l up to L-20; M-l through L-19; M-l through T-18; M-1 to P-17; M-l through V-16; M-1 to P-15; M-1 to G-14; M-l through F-13; M-l through S-12; M-1 to R-11; M-1 to S-10; M-1 to G-9; M-1 to P-8; M-1 through A-7; of the SEC. ID NO. 2. For example, any of the N-or C-terminal deletions listed above can be combined to produce a deleted METH1, N- or C-t linear polypeptide.

In addition, N-terminal deletions of the METH2 polypeptide can also be described by the general formula m-890, where n is an integer from 2 to 889, where m corresponds to the position of the amino acid residue identified in SEC. ID NO. 4. Preferably, the N-terminal deletions of the METH2 polypeptide of the invention are shown as l ^ SEC. ID NO. 4 include the polypeptides comprising the amino acid sequence of the residues: F-2 to L-890; P-3 to L -890; A - 4 to L-890; P-5 to L-890; A- 6 to L-890; A-7 to L-890; P-8 to L -890; R-9 to L-890; W-10 to L-890; L-11 to L-890; P-12 to L-890; F-13 to L-890; L-14 to L-890; L-15 to L-890; L -16 to L-890; L-17 to L-890; L-18 to L-890; L-19 to L-890 L-20 to L-890; L-21 to L-890; L-22 has'ta L-890; P-23 to L-890; 1-24 to L-890; A-25 to L-890; - -R-26 to L-890; G-27 to L-890; A-28 to L-890; P-29 to L-890; A-30 to L -890; R-31 to L-890; P-32 to L-890; A-33 to L-890; A-34 to L-890; G-35 to L-890; G-36 to L-890; Q-37 to L-890; A-38 to L-890; S-39 to L-890; E-40 to L-890; L-41 to L-890; V-42 to L -890; V-43 to L-890; P-44 to L-890; T -45 to L-890; R-46 to L-890; L-47 to L-890; P-48 to L-890; G-49 to L-890; S-50 to L-890; A- 51 to L-890; G-52 to L-890; E-53 to L-890; L-54 to L -890; A-55 to L-890; L-56 to L-890; H-57 to L-890; L-58 to L-890; S-59 to L-890; A-60 to L-890; F-61 to L-890; G-62 to L-890; K-63 to L-890; G-64 to L-890; F-65 to L-890; V-66 to L -890; L-67 to L-890; R-68 to L-890; L-69 to L-89Q; A-70 to L-890; P-71 to L-890; D-72 to L-890; D-73 to L-890; S-74 to L-890; F-75 to JL-890; L-76 to L-890; A-77 to L-890; P-78 to L -890; E-79 to L-890; F-80 to L-890; K -81 to L-890; 1-82 to L-890; E-83 to L-890; R-84 to L-890; L-85 to L-890; G-86 to L-890; G-87 to L-890; S-88 to L-890; G-89 to L-890; R-90 to L -890; A-91 to L-890; T-92 to L-890; G -93 to L-890; G-94 to L-890; E-95 to L-890; R-96 to L-890; G-97 to L-890; L-98 to L-890; R-99 to L-890; G-100 to L-890; C-101 to L-890; F-102 to L-890; F-103 to L-890; S-104 to L-890; G-105 to L-890; T-106 to L-890; V-107 to L-890; N-l 08 to L-890; G-109 up L-890; E-110 to L-890; P-III up to L-890; E-112 to L-890; S-113 to L-890; L-114 to L-890; A-115 to L-890; A- 116 up L-890; V-117 to L-890; S-118 to L-890; L-119 to L-890; C-120 to L-890; R-121 to L-890; G-122 to L-890; L-123 up L-890; S-124 to L-890; G-125 to L-890; S-126 to L-890; F-127 to L-890; L-128 to L-890; L-129 to L-890; D-130 to L-890; G-131 to L-890; E-132 to L-890; E-133 to L-890; F-134 to L-890; T-135 to L-890; 1-136 to L-890; Q-137 up L-890; P-138 to L-890; Q-139 to L-890; G-140 to L-890; A-141 to L-890; G-142 to L-890; G-1 3 to L-890; S-144 to - - L-890; L-145 to L-890; -146 antler L-590; Q-147"up to L-890, P-148 up to L-S90, K-l 9 up to L-890, R-150 up to L-890, L-151 up L-890; Q-152 to L-890; R-153 to L-890; W-154 to L-890; G-155 to L-890; P-156 to L-890; A-157 to L-89Q; G-158 up L-890; A-159 to L-890; R-l 60 to L-890; P-161 to L-890; L-162 to L-890; P-163 to L-890; R-164 to L-890; G-165 antler L-890; P-166 to L-89Q; E-167 to L-Ó90; W-168 to L-890; E-169 to L-890; V-170 to L-890; E-171 to L-890; T-172 up L-890; G-173 to L-890; L-174 to L-890; G-175 to L-890; Q-176 to L-890; R-177 to L-890; Q-178 to L-890; E-179 up L-890; R-180 to L-890; G-181 to L-890; D-182 to L-890; H-183 to L-890; Q-184 to L-890; E-185 to L-890; D-186 up L-890; S-187 to L-890; E-188 to L-890; E-18.9 to L-890; E-190 to L-890; S-191 to L-890; Q-192 to L-890; E-193 up L-890; E-194 to L-890; E-195 to L-890; A-196 to L-890; E-197 to L-890; G-198 to L-890; A-199 to L-890; S-200 to L-890; E-201 to L-890; P-202 to L-890; - - P-203 to "L-890, P-204 to L-890, P-205 to L-890, L-206 to L-890, G-207 to L-890; A-208 to L-890; T-209 to L-890; S-210 to L-890; R-211 to L-890; T-212 to L-890; K-213 to L-890; R-214 up L-890; F-215 to L-890; V-216 to L-890; S-217 to L-890; E-218 to L-890; A-219 to L-890; R-220 to L-890; F-221 up L-890; 'V-222 to L-890; E-223 to L-890; T-224 to L-890; L-225 to L-890; L-226 to L-890; V-227 to L-890; A-228 up L-890; D-229 to L-890; A-230 to L-890; S-231 to L-890; M-232 to L-890; A-233 to L-890; A-234 to L-890; F-235 to L-890; Y-236 to L-890; G-237 to L-890; A-238 to L-890; D-239 to L-890; L-240 to L-890; Q-241 to L-890; N-242 up L-890; H-243 to L-890; 1-244 to L-890; L-245 to L-890; T-246 to L-890; L-247 to L-890; M-248 to L-890; S-249 up L-89U; V-250 to L-890; A-251 to L-890; A-252 to L-890; R-253 to L-890; 1-254 to L-890; Y-255 to L-890; K-256 up L-890; H-257 to L-890; P-258 to L-890; S-259 to L-890; 1-260 to L-890; K-261 - -up to L-890; N-262 to L-890; S-263 up L-890; 1-264 to L-890; N-265 to L-890; L-266 to L-890; M-267 to L-890; V-268 to L-890; V-269 to L-890; K-270 up L-890; V-271 to L-890; L-272 to L-890; 1-273 to L-890; V-274 to L-890; E-275 to L-890; D-276 to L-890; E-277"up L-890; K-278 to L-890; W-279"up to L-890; G-280 to L-890; P-281 to L-890; E-282 to L-890; V-283 to L-89-0; S-284 up L-890; D-285 to L-890; N-286 to L-890; G-287 to L-890; G-288 to L-890; L-289 to L-890; T-290 to L-890; L-291 up L-890; R-292 to L-890; N-293 to L-890; F-294 to L-890; C-295 to L-890; N-296 antler L-850; W-297 to L-890; Q-298 up L-89Q; R-299 to L-890; R-300 to L-890; F-301 to L-890; N-302 to L-890; Q-303 to L-890; P-304 to L-890; S-305 to L-890; D-306 to L-890; R-307 to L-890; H ^ 308 to L-890; P-309 to L-890; E-310 to L-890; H-311 to L-890; And -312 up L-890; "D-313 to L-890; T-314 to L-890; A- 315 to L-890; 1-316 to L-890; L-317 to L-890; L-318 to L-890; T-319 to - L-890; R-320 to L-890; Q-321 to L-890-; N-322 to L-890; F-323 to L-890; C-324 to L-890; G-325 to L-890; Q-326 up L-890; E-327 to L-890; G-328 to L-890; L-329 to L-890; C-330 to L-890; D-331 to L-890; T-332 to L-890; L-333 up L-890; G-334 to L-890; V-335 to L-890; A- 336 up to L-890; D-337 to L-890; 1-338 to L-890; G-339 to L-890; T-340 to L-890; 1-341 to L-890; C-342 to L-890; D-343 to L-890; P-344 to L-890; N-345 to L-890; 'K-346 to L-890; S-347 up L-890; C-348 to L-890; S-349 to L-890; V-350 to L-890; 1-351 to L-890; E-352 to L-890; D-353 to L-890; E-354 up L-890; G-355 to L-89Q; L-356 to L-890; Q-357 to L-890; A-358 to L-890; A-359 antler L-890; H-360 to L-890; T-361 up L-890; L-362 to L-890; A-363 to L-890; H-364 to L-890; E-365 to L-890; L-366 to L-890; G-367 to L-890; H-368"up L-890; V-369 to L-890; L-370 to L-890; S-371 to L-890; M-372 to L-890; P-373 to L-890; H-374 to L-890; D-375 to L-890; D-376 to L-890; S-377 to L-890; K-378 to L-890; P-379 to L-890; C-380 to L-890; T-381 to L-890; R-382 up L-89Q; L-383 to L-890; F-384 to L-890; G-385 to L-890; P-386 to L-890; M-387 ftk 5 to L-890; G-388 to L-890; K-389 up L-890; H-390 to L-890; H-391 to L-890; V-392 to L-890; M-393 to L-890; A-394 to L-890; P-395 to L-890; L-396 up L-89Q; F-397 to L-890; V-398 to L-890; 10 H-399 to L-890; L-400 to L-890; N-401 to L-890; Q-402 to L-890; T-403 up L-890; L * - 4 O 4 to L-890; P405 to L 89 O; W-406 to L-890; S-407 to L-890; P-408 to L-890; C-409 to L-890; S-410 up 15 L-890; A-411 to L-890; M-412 to L-890; Y-413 to L-890; L-414 to L-890; T-415 to L-890; E-416 to L-890; L-417 up L-890; L-418 to L-890; D-419 to L-890; G-420 to L-890; G-421 to L-890; H-422 20 to L-890; G-423 to L-890; D-424 up L-890; C-425 to L-890; L-426 to L-890; L-427 to L-890; D-428 to L-890; A-429 to L-890; P-430 to L-890; G-431 up L-890; A-432 to L-890; A-433 to L-890; 25 L-434 to L-890; P-435 to L-890; L-436 - -up to L-890; P-437 to L-890; T-438 up L-890; G-439 to L-890; L-440 to L-790; P-441 to L-890; G-442 to L-890; R-443 to L-890; M-444 to L-890; A-445 up L-890; L-446 to L-890; Y-447 to L-890; Q-448 to L-890; L-449 to L-890; D-450 to L-890; Q-451 to L-890; Q-452 up L-890; C-453 to L-890; R-454 to L-890; Q-455 to L-890; 1-456 to L-890; F-457 to L-890; G-458 to L-890; P-459 to L-890; D-460 to L-890; F-461 to L-890; R-462 to L-890; H-463 to L-890; C-464 to L-890; P-465 to L-890; N-466 to L-890; T-467 to L-890; S-468 to L-890; A-469 to L-890; Q-470 to L-890; D-471 to L-890; V-472 to L-890; C-473 to L-890; A-474 to L-890; Q-475 to L-890; L-476 to L-890; W-477 to L-890; C-478 to L-890; H-479 to L-890; T-480 to L-890; D- 81 to L-890; G-482 to L-890; A-483 to L-890; E-484 to L-890; P-485 to L-890; L-486 to L-890; C-4S7 to L-890; H-488 to L-890; T-489 to L-890; K-490 to L-890; N-491 to L-890; G-492 to L-890; S-493 to L-890; L-494 to - - L-890; P-495 to L-890; W-496 to L-890; A- 497 to L-890; D-498 to L-890; G-499 to L-890; T-500 to L-890; P-501 up L-890; C-502 to L-890; G-503 to L-890; P-504 to L-890; G-505 to L-890; H-506 to L-890; L-507 to L-890; C-508 up L-890; S-509 to L-890; E-510 to L-890; G-511 to L-890; S-512 to L-890; C-513 to L-890; L-514 to L-890; P-515 to L-890; E-516 to L-S90; E-517 to L-890; E-518 to L-890; V-519 to L-890; E-520 to L-890; R-521 to L-890; P-522 up L-890; K-523 to L-890; P-524 to L-890; v-525 to L-890; V-526 to L-890; D-527 to L-890; G-528 to L-890; G-529 up L-890; W-530 to L-890; A-531 to L-890; P-532 to L-890; W-533 to L-890; G-534 antler L-890; P-535 to L-890; W-536 up L-890; G-537 to L-890; E-538 to L-890; C-539 to L-890; S-540 to L-890; R-541 to L-890; T-542 to L-890; C-543 up L-890; G-544 to L-890; G-545 to L-890; G-546 to L-890; V-547 to L-890; Q-548 to L-890; F-549 to L-890; S-550 to L-890; H-551 to L-890; R-552 to L-890; E-553 up to "L-890; C-554 up to L-890; K-555 up to L-890; D-556 up to L-890; P-557 up L-890; E-558 to L-890; P-559 to L-890; Q-560 to L-890; N-561 to L-890; G-562 to L-890; G-563 to L-890; R-564 up L-890; And -565 to L-890; C-566 to L-890; L-567 to L-890; G-568 to L-890; R-569 to L-890; R-570 to L-890; A-571 up L-890; K-572 to L-890; And -573 to L-890; Q-574 to L-890; S-575 to L-890; C-576 to L-890; H-577 to L-890; T-578 nasta L-890; E-579 to L-890; E-580 to L-890; C-581 to L-890; P-582 to L-a90; P-583 to L-890; D-584 to L-890; G-585 to L-890; K-586 to L-890; S-587 to L-890; F-588 to L-890; R-589 to L-890; E-590 to L-890; Q-591 to L-890; Q-592 up L-890; C-593 to L-890; E-594 to L-890; K-595 to L-890; And -596 to L-890; N-597 to L-890; A-598 to L-890; And -599 up L-890; N-600 to L-890; Y-601 to L-890; T-602 to L-890; D-603 to L-890; M-604 to L-890; D-605 to L-890; G-606 up L-890; N-607 to L-890; 1-608 to L-890; L-609 to L-890; - Q-610 to L-890; W-611 to L-890; L-612 to L-890; P-613 up L-890; K-614 to L-890; And -615 to L-890; A-616 to L-890; G-617 to L-890; V-618 to L-890; S-619 to L-890; P-620 up L-890; R-621 to L-890; D-622 to L-890; R-623 to L-890; "C-624 to L-890, K-625 to L-890, L-626 to L-89'0, F-627" to L-890; 'C-628 to L-890; R-629 to L-890; A- 630 to L-890; R-631 to L-890; G-632 to L-890; "R-633 to L-890; S-634 'to L-890; E-635 to L-890; F-636 to -L-890; K-637 to L-890; V-638 to L-890; F-639 to L-890; E-640 to L-890; A-641 up L-890; K-642 to L-890; V-643 to L-890; 1-644 to L-890; D-645 to L-890; G-646 to L-890; T-647 to L-890; L-648 up L-890; C-649 to L-890; G-650 up to "L-890; P-651 to L-890; E-652 to L-890; T-653 to L-890; L-654 to L-890; A-655 up L-890; 1-656 to L-890; C-657 to L-890; V-658 to L-890; R-659 to L-890; G-660 to L-890; Q-661 to L-890; C-662"up L-890; V-663 to L-890; K-664 to L-890; A-665 to L-890; G-666 to L-890; C-667 to L-890; D-668 to L-890; H-669 to L-89Q; V-670 to L-890; V-671 to L-890; D-672 to L-890; S-673 to L-890; P-674 to L-890; R-675 to L-890; K-676 up L-890; L-677 'up to L - to 9 Q; D-678 to L-890; K-679 to L-890; C-680 to L-890; G-681 to L-890; V-682 to L-890; C-683 up L-890; G-684 to L-890; G-685 antler L-890; K-686 to L-890; G-687 to L-89Q; N-686 to L-890; S-689 to L-890; C-690 up L-890; R-691 to L-890; K-692 to L-b 90; V-693 to L-890; S-694 to L-890; G-695 to L-890; S-696 to L-890; L-697 to L-890; T-698 to L-890; P-699 to L-890; T-700 to L-890; N-701 to L-890; Y-702 to L-890; G-703 to L-890; Y-704 to L-890; N-705 to L-890; D-706 to L-890; 1-707 to i-890; V-708 to L-890; T-709 to L-890; 1-710 to L-890; P-711 to L-890; A-712 to L-890; G-713 to L-890; A- 714 to L-890; T-715 nasta L-890; "N-716 to L-890, 1-717 to L-890, D-718 to L-890, V-719 to L-890, K-720 to L-890, Q-721 to L-890; -722 to L-890, S-723 to L-890, H-724 to L-89Q, P-725 to L-890, G-726 to L-890, V-727 to L-890; Q-728 to L-890; N-729 to L-890; D-730 to L-890; G-731 to L-890; N-732 to L-890; Y-733 to L-890; L-734 to L-890; A- 735 to L-890; L-736 to L-890; K-737 to L-890; T-738 to L-890; A-739 to L-890; D-740 to L-890; G-741 to L-890; Q-742 to L-890; Y-743 to L-890; L-744 to L-890; L-745 to L-890; N-746 to L-890; G-747 to L-890; N-748 to L-890; L-749 to L-890; A-750 to L-890; 1-751 to L-890; S-752 to L-890; A-753 to L-890; 1-754 to L-890; E-755 to L-890; Q-756 to L-890; D-757 to L-890; 1-758 to L-890; L-759 to L-890; V-760 to L-890; K-761 to L-890; G-762 to L-890; T-763 to L-890; 1-764 to L-890; L-765 to L-890; K-766 to L-890; Y - l 1 up L-890; S-768 to L-890; G-769 to L-890; S-770 to L-890; 1-771 to L-890; ? -772 to L-890; T-773 to L-890; L-774 up L-890; E-775 to L-890; R-776 to L-890; - l l l to L-890; Q-778 to L-890; S-779 to L-890; F-780 to L-890; R-781 up L-890; P-782 to L-890; L-783 to L-890; P-784 to L-890; E-785 to L-890; P-786 - up to L-890; L-787 to L-890; T-788 up L-890; V-789 to L-890; Q-790 to L-890; L-791 to L-890; L-792 to L-890; T-793 to L-890; V-794 to L-890; P-795 up L-890; G-796 to L-890; E-797 to L-890; V-798 to L-890; F-799 to L-890; P-800 to L-890; P-801 to L-890; K - 802 ~ "up L-890; V-803 to L-890; K-804 to L-890; Y-805 to L-890; T-806 to L-890; F-807 to L-890; F-808 to L-890; V-809 up L-890; P-810 to L-890; N-811 to L-890; D-812 to L-890; V-813 to L-890; D-814 to L-890; F-815 to L-890; S-816 up L-890; M-817 to L-890; Q-818 to L-890; S-819 to L-890; S-820 to L-890; K-821 to L-890; E-822 to L-890; R-823 up L-890; A-824 to L-890; T-825 to L-890; T-826 to L-890; N-827 to L-890; 1-828 to L-890; 1-829 to L-890; Q-830 up L-890; P-831 to L-890; L-832 to L-890; L-833 to L-890; H-834 to L-890; A-835 to L-890; Q-836 to L-890; W-837 up L-890; V-838 to L-890; L-839 to L-890; G-840 to L-890; D - 841 to L-890; W-842 to L-890; S-843 to L-890; E-844 to - - L-890; C-845 to L-890; S-846 to L-890; S-847 to L-890; T-848 to L-890; C-849 to L-890; G-850 to L-890; A- 851 to L-890; G-852 to L-890; W-853 to L-890; Q-854 to L-89Q; R-855 to L-890; R-856 to L-890; T-857 to L-890; V-858 to L-890; E-859 to L-890; C-860 antler L-890; R-86I antler L-890; D-862 to L-890; F-563 to L-890; S-864 'to L-890; G-865 to L-S90; Q-866 to L-890; A-867 to L-890; S-868 nasta L-890; A-869 to L-890; T-870 to L-890; C-671 to L-890; N-872 to L-890; K-873 to L-890; A-874 to L-890; L-875 to L-890; K-876 to L-890; P-877 to L-890; E-878 to L-890; D-879 to L-890; A-880 to L-890; K-881 to L-890; P-882 to L-890; C-883 to L-890; E-884 paste L-890; S-665 to L-890; of the SEC. ID NO. Four.

In addition, the C-terminal deletions of the METH2 polypeptide can also be dexied by the general formula 1-n, where n is an integer from 2 to 890, where n corresponds to the position - of the amino acid residue identified in the SEC. ID NO. 4. Preferably, the C-terminal deletions of the METH2 polypeptide of the invention show as SEC. ID NO. 4 includes the polypeptides comprising the amino acid sequence of the residues: M-1 to P-889; M-l to C -888; M-1 to L-887; M-1 to Q-886; M-1 to S-885; M-1 to E-884; M-1 to C-883; M-1 to P-882; M-1 to K-881; M-i up to A-880; M-1 to D-879; M-l to E -878; M-1 to P-877; M-l Asta K-876; M-l up to L-875; M-1 through A-874; M-1 to K-873; M-1 to N-872; M-1 to C-871; M-l up to T-870; M-1 through A-869; M-1 to S-866; M-i to A-867; M-1 to Q-866; M-1 to G-865; M-1 to S-864; M-1 to P-863; M-1 to D-862; M-1 to R-861; M-1 to C-860; M-1 to E-859; M-i to V -858; M-l up to T-657; M-1 to R-856; M-1 to R-855; M-1 to Q-854; M-l to W -853; M-1 to G-852; M-1 to A-851; M-1 to G-850; M-i up to C-849; M-l to T -848; M-1 to S-847; M-1 to S-846; M-1 to C-845; M-1 to E-844; M-1 to S- - 843; M-l through W-842; M-1 to D-841; M-1 to G-840; M-l to L-839; M-1 to V -838; M-l through W-837; M-1 to Q-836; M-1 to A-835; M-1 through H-834; M-1 to L-833; M-1 to L-832; M-1 to P-831; M-l up to Q-830; M-1 to 1-829; M-1 through I -828; M-1 to N-827; M-l through T-826; M-l up to T-825; M-1 to A-824; M-1 to R -823; M-1 through E-822; M-l to K-821; M-1 to S-820; M-1 to S-819; M-l to Q -818; M-I to M-817; M-1 to S-816; M-l nasta F-815; M-1 to D-814; M-1 to V -813; M-1 to D-812; M-1 to N-811; M-1 to P-810; M-1 to V-809; M-1 to F-808; M-1 to F-807; M-l through T-8Q6; M-1 to Y-805; M-1 to K-804; M-1 to V-803; M-1 to K-802; M-1 to P-801; M-1 to P-800; M-i up to F-799; M-1 to V-798; M-1 to E-797; M-1 to G-796; M-1 to P-795; M-1 to V-794; M-l to T -793; M-1 to L-792; M-1 to L-791; M-l nasta Q-790; M-1 to V-789; M-i up to T-788; M-1 to L-787; M-1 to P-786; M-l to E-785; M-i up to P-764; M-1 to L-783; M-1 to P-782; M-1 to R-781; M-l - up to F-780; M1 to S779, M1 to Q778; M-1 to L-777; M-1 to R-776; M-1 to E-775; M-1 to L-774; M-1 to T-773; M-l to A- 7.72; M-1 to 1-771; M-1 to S-770; M - 1 to G-769; M-1 to S-768; M-l through Y-767; M-1 to K-766; M-1 to -765; M - i to 1-764; M-1 to T-763; M-1 to G-762; M-l through K-762; M-1 to V-760; M-1 'to L-759; M-1 to I-758; M-i up to ~ D-757; M-l to Q-756; M-i n sta E-755; M -1 to 1-754; M-1 to A-753; M-1 to S-752; M-1 to 1-751; M-1 to A-750; M- • 1 to L-749; M-l to N -748; M-1 to G-747; M-1 to N-746; M-l to L-745; M - • 1 to L-744; M-l to Y -743; M-1 to Q-742; M-1 to G-741; M-1 to D-740; M-1 to A-739; Ml to T - "38; Ml to K-737; Ml to L-736; Ml to A-735; M-1 to L-734; Ml to Y-733; Ml to N-732; Ml to G-731;; Ml to D-730; M - I to N-729; Ml to Q -728; Ml to V-727; Ml to G-726; Ml to P-725; M-1 to H-724; Ml to S -723, Ml to R-722, Ml to Q-72T, Ml to K-720, M-1 to V-719, Ml to D- - 718, Ml to 1-717, Ml to N-716, Ml to T-715; Ml up to A-714; Ml up to G-713; Ml up to A-712; Ml up to P-711; Ml up to 1-710; Ml up to T-709; Ml up to V-708; Ml up to 1- 707; Ml to D-706; Ml to N-7 0 5; M-1 to Y-704; Ml to G-703; Ml to Y-702; Ml to N-701; Ml to T-700; M - 1 to P-699, Ml to T -698, Ml to L-697, Ml to S-696, Ml to G-695, M-1 to S-694, Ml to V -693, Mi to K-692; Ml to R-69T, Ml to C-690, M-1 to S-689, Ml to N -688, Ml to G-687, Ml to K-686, Ml to G-685, M-1 to G- 684; Ml to C -683; Ml hast to V-682; M-1 to G-681; M-l to C-680; M-1 to K-679; Ml to D -678, "Ml to L-677, Ml to K-676, Ml to R-675, M-1 to P-674, Ml to S -673, Ml to D-.672, Ml to V- 671, Ml to V-670, M-1 to H-669, Ml to D -668, Mi to C-667, Ml to G-666, Ml to A-665, M-1 to K-664, Ml to V -663; Ml up to C-662; Ml up to Q-661; Ml up to G-660; M-1 up to -R-659; Ml up to V -658; Ml up to C-657; Ml up to 1-656; Ml - -up to A- 655, Ml up to L-654, Ml up to T-653, Ml up to E-652, Mi up to P-651, Ml up to G-650, M-1 up to C-649, Ml up to L -648; Ml to T-647; Ml to G-646; Ml to D-645; M-1 to 1-644; Ml to V -643; Ml to K-642; Ml to A-641; Ml to E-640;; M-1 to F-639; Ml to V -638; Ml to K-637; Ml to F-636; Ml to E-635; M-1 to S-634; Ml to R-633; Ml to G -632, Ml to R-631, Ml to -630, M-1 to R-629, Ml to C -628, Ml to F-627, Ml to L-626, Ml to K-625, M-1 to C-624; Ml up to R -623; Ml up D-622; M-1 to R-621; M-1 to P-620, M-1 to S-619; M-l through V-618; M-l antler G-617; M-1 through A-616; M-1 through Y-615; M-1 to K-614; M-1 to P -613; M-1 to V-612; M-i up to W-611; M-l through Q-610; M-1 to L-609; M-l to L -608; M-1 to N-607; M-1 to G-606; M-1 to D-605; M-1 to M-604; M-1 to D-603; M-1 to T-602; M-l through Y -601; M-1 to N-600; M-1 to Y-599; M-l up to A-598; M-1 to N-597; M-1 through Y-596; M-1 to K-595; M-1 to E-594; M-1 to C-- - - 593; M-1 through Q-592; M-1 through Q-591; M-1 to E-590; M-i to R-589; M-1 to F-588; M-1 to S-587; M-1 to K-586; M-1 to G-585; M-1 to D-584; M-1 to P-563; M-1 to P-582; M-1 to C-581; M-i up to E-580; M-1 to E-579; M-l up to T-578; M-1 H-577; M-1 to C-5 6; M - I through S-575; M-i up to Q-574; M-l nasta Y -573; M-1 to K-572; M-1 to A-571; M-1 to R-570; M-1 to R-569; M-1 to G-6-; up to -567; M-1 to C-566; M-l sta sta R-564; M-1 to G-563; M-l nasta G-562; M-1 to N-561; M-l paste Q-560; M-i up to P-559; M-1 to L-556; M-1 to P-55; M-1 to D-556; M-1 to K-555; K-l antler C-554; M-1 to E-553; M-1 to R-552; M-1 to H-551; M-l r a s t a S-550; M-1 to F-549; M-1 to Q-548; M-1 flag V-547; M-1 to G-546; M-1 to G-545; M-1 to G-544; M-1 to C-543; M-1 through T-542; M-1 to R-541; M-l hastd S-540; M-1 through C-539; M-l to E -538; M-1 to G-537; M-1 to V-536; M-1 to P-535; M-1 to G-534; M-1 to W-533; M-1 to P-532; M-1 to A-531; M-l - antler W-530; M-l antler G-529; M-1 to G-528; M-1 to D-527; M-i to V-526; M-1 to V-525; M-1 to P-524; M-1 to K-523; M-1 to P-522; M-1 to R-521; M-l up to E-520; M-1 to V-519; M-1 to P-518; M-1 through E-517; M-l through E-516; M-i to P-515; M - -i to L-514; M-1 to C-513; M-l antler S-512; M-1 to G-5L1; M-1 to E-510; M • -1 to S-509; M-1 to C-508; M-i up to L-507; M-i to H-506; M-1 to G-505; M-1 to P-504; M-1 to G-503; M-1 to C-502; M-l has a P-501; M-l up to T-500; M - • 1 antler G-499; M-1 to D-498; M-l through A-497; M-l through W-496; M-1 to P-495; M - • 1 to L-494; M-1 to S-493; M-i to G-492; M-1 to N-491; M-i up to K-490; M-1 to T-489; M-l up to H -4 Y 'ó; M-l to C-49 ~; M-1 to L-486; M-1 to P-485; M-1 to E-484; M-1 to A-483; M-1 to G-482; M-l antler D-461; M-l up to T-450; M - i nasta H-479; M-l to C -478; M-i to K-477; M-1 to L-476; M-1 to Q-475; M-1 to A-4 4; M-1 to C -473; M-1 to V-472; M-i to D-471; M-l to Q-470; M-1 to A-469; M-1 to S- - - 468; M-l through T-467; M-1 to N-466; M-l nasta P-465; M-i nasta C-464; M-1 to H -463; M-1 to R-462; M-l antler F-461; M-l antler D-460; M-l antler P-459; M-l to G -458; M-1 to F-457; M-1 to 1-456; M-1 to Q-455; M-1 to R-454; M-i up to C -453; M-l antler Q-452; M-1 to Q-451; M-1 to D-450; M-1 to L-449; M-l nasta Q -448; M-1 to Y-447; M-1 to L-446; M-l h sta A-445; M-1 to M-444; M-1 to R-443; í -'- l to G-442; M-1 to P-441; M-i up to L-440; K-l to G-439; M-l up to T -438; M-1 to P-437; M-1 to L-436; M-1 to P-435; M-i to L-434; M-i to A-433; M-i to A-432; M-1 to G-431; M-1 to F-430; M-1 to A-429; M-1 to D -428; M-1 to L-427; M-1 to L-426; M-l 'i a s t a 425; M-I to D-424; M-1 to G-423; M-i to H-422; M-i to G-421; M-1 to G-420; M-1 to D-419; M-1 to L-416; M-1 to L-417; M-1 through E-416; M-1 to 1-15; M-I through L-414; M-1 to Y-413; M-i to M-412; M-1 through A-411; M-l h sta S-410; M-i up to C-409; M-i to P-406; M-I to S-407; M-l to W-406; M-1 - - up to P-405; M-l to L-404; M-1 to T-403; M-1 to Q-402; M-1 to N-401; M-l up to L-400; M-l to H-399; M-1 to V-398; M-1 to F-397; M-1 to L-396; M-1 to P-395; M-1 to A-394; M-1 to M-393; M-1 to V-392; M-1 to H-391; M-1 to H-390; M-i up to K-359; M-l nasta G -388; M-l to M-387; M-1 to P-386; M-1 to G-385; M-1 to F-384; M-1 to L-383; M-1 to R-382; M-l through T-381; M-l up to C-380; M-1 to P-379; M-l to K -378; - M-l to S-377; M-1 to D-376; M-1 to D-375; M-i to H-374; M-1 to P -373; M-1 to M-372; M-1 to S-371; M-l up to L-370; M-1 to V-369; M-1 to H -368; M-l to G-367; M-i to L-366; M-1 to B-365; M-1 to H-364; M-1 to A-363; M-1 to L-362; M-l nasta T-361; M-i to N-360; M-1 to A-359; M-1 to A-358; M-1 to Q-357; M-1 to L-356; M-l to G-355; M-i to E-354; M-1 to D -353; M-1 to E-352; M-I to 1-351; M-1 to V-350; M-i to S-349; M-1 to C -348; M-1 to S-347; M-1 to K-346; M-1 to N-345; M-1 to P-344; M-1 to D- - - 343; M-1 to C-342; M-1 to 1-341; M-l up to T-340; M-1 to G-339; M-1 to I-338; M-1 to D-337; M-1 to A-336; M-1 to V-335; M-1 to G-334; M-l to L -333; M-1 to T-332; M-1 to D-331; M-1 to C-330; M-1 to L-329; M-1 to G-328; M-1 to E-327; M-1 to Q-326; M-1 to G-325; M-1 to C-324; M-1 to F-323; M-1 to N-322; M-1 to Q-321; M-1 to R-320; M-1 to T-319; M-1 to L -318; M-1 to L-317; M-1 to 1-316; M-1 to A-315; M-1 to T-314; M-1 to D-313; M-1 to Y-312; M-1 to H-311; M-1 to E-310; M-1 to P-309; M-1 to H -308; M-1 to R-307; M-1 to D-306; M-1 to S-305; M • 1 to P-304; M-1 to Q-303; M-1 to N-302; M-1 through F-301; M-1 to R-300; M-1 to R-299; M-1 to Q-298; M-l through W-297; M-1 to N-296; M-1 to C-295; M-1 to F-294; M-1 to N-293; M-1 to R-292; M-1 to L-291; M-1 to T-290; M-1 to L-289; M-1 to G-288; M-1 to G-287; M-1 to N-286; M-1 to D-285; M-1 to S-284; M-1 through V-283; M-1 through E-282; M-1 to P-281; M-1 - - up to G-280; M-l through W-279; M-l to K -278; M-1 through E-277; M-1 to D-276; M-1 through E-275; M-1 to V-274; M-1 to I-273; M-1 through L-272; M-1 through V-271; M-l to K-270; M-1 to V-269; M-1 to V-268; M-1 to M-267; M-1 to L-266; M-1 to N-265; M-1 to 1-264; M-1 to S-263; M-1 to N-262; M-1 to K-261; M-1 to 1-260; M-1 to S-259; M-1 to P-258; M-1 to H-257; M-1 to K-256; M-l to Y-255; M-1 to 1-254; M-1 to R-253; M-1 to A-252; M-1 to A-251; M-1 to V-250; M-1 to S-249; M-l to M -248; M-1 to L-247; M-l through T-246; M-1 to L-245; M-1 to 1-244; M-1 to H-243; M-1 to N-242; M-1 through Q-241; M-l to L-240; M-1 to D-239; M-1 through A-238; M-1 to G-237; M-1 through Y-236; M-1 to F-235; M-1 to A-234; M-1 through A-233; M-1 to M-232; M-1 to S-231; M-1 to A-230; M-1 to D-229; M-1 through A-228; M-1 to V-227; M-1 to L-226; M-1 to L-225; M-l through T-224; M-l to E -221; M-1 to V-222; M-1 through F-221; M-1 to R-220; M-l to A-219; M-l to E- - - 21 M-l to S-217 M-l to V-216 M-1 to F-215; M -1 to R-214; M-1 to K-213; M-1 to T-212, M-1 to R-211; M-1 to S-210; M-1 to T-209; M • 1 to A- 208; M-1 to G-207; M-1 to L-206; M-1 to P-205; M-1 to P-204; M -1 to P- 203; M-1 to P-202; M-l to E-201; M-1 to S-200; M-1 to A-199; M-1 to G-198; M-1 through E-197; M-l up to A-196; M-l through E-195; M • 1 to E-194; M -1 to E- 193; M-l to Q-192; M-1 through S-191; M-l to E-190; M-1 to E-189; M-1 to E-188; M-1 through S-187; M-1 to D-186; M-l to E-185; M-1 to Q-184; M • 1 to H- 183; M-1 to D-182; M-1 to G-181; M-1 to R-180, M-1 to E-179; M-l to Q -178; M-1 to R-177; M-l to Q-176; M-1 to G-175; M-1 to E-174; M-l to G -173; M-l through T-172; M-l through E-171; M-1 to V-170; M-l 'up to E-169; M-l to W -168; M-l through E-167; M-1 to P-166; M-1 to G-165; M-1 to R-164; M-l to P -163; M-'l to L-162; M-1 to P-161; M-l up to R-160; ' M-1 through A-159; M-1 to G-158; M-1 to A-157; M-1 to P-156; M-l - -up to G-155; M-1 to W-154; M-1 to R -153; M-1 to Q-152; M-1 to L-151; M-1 to R-150; M-1 to H-149; M-1 to P-148; M-l to Q-147; M-1 to A-146; M-1 to L-145; M-1 to S-144; - 1 to G -143; M-1 to G-142; M-1 to A-141; M-1 to G-140; M-1 to Q-139; M-1 to P -138; M-1 to Q-137; M-1 through 1-136; M-l up to T-135; M-1 to F-134; M-1 to E -133; M-1 to E-132; M-1 to G-131; M-1 to D-130; M-1 to L-129; M-l to L -128; M-l through F-127; M-1 to S-126; M-1 to G-125; M-1 to S-124; M-1 to L-123; M-l up to G-122; M-1 to R-121; M-1 to C-120; M-1 through L-119; M-1 to S-118; M-1 to V-117; M-1 to A-116; M-1 to A-115; M-1 to L-14; M-1 to S-113; M-1 to E-112; M-l to P-III; M-l to E-110; M-1 to G-109; M-1 to N -108; M-1 to V-107; M-1 to T-106; M-1 to G-105; M-1 to S-104; M-l to F -103; M-l through F-102; M-1 to C-101; M-1 to G-100; M-1 to R-99; M-l through L-98; M-l to G-97; M-1 to R-96; M-l to E -95; M-l to G-94; M-1 to G-93; M-l - -up to T-92; M-1 to A-91; M-1 to R-90; M-l to G-89; M-1 to S-88; M-l to G-87; M-1 to G-86; M-l up to L-85; M-1 to R-84; M-l through E-83; M-1 to 1-82; M-1 to K-81; M-l through F-80; M-l to E-79; M-1 to P-78; M-1 to A-77; M-l to L-76; M-1 to F-75; M-1 to S-74; M-l to D-73; M-1 to D-72; M-1 to P-71; M-l up to A-70; M-l through L-69; M-1 to R-68; M-l to L-67; M-1 to V-66; M-l through F-65; M-l through G-64; M-l to K -63; M-l to G-62; M-l through F-61; M-1 to A-60; M-1 to S-59; M-l up to L-58; M-1 to H-57; M-l up to L-56; M-l up to A-55; M-l through L-54; M-l through E-53; M-1 to G-52; M-1 to A-51; M-1 to S-50; M-l to G-49; M-1 to P-48; M-1 to L-47; M-1 to R-46; M-l up to T-45; M-1 to P-44; M-l through V-43; M-1 to V-42; M-l up to L-41; M-l through E-40; M-1 to S-39; M-1 to A-38; M-l up to Q-37; M-l to G-36; M-l up to G-35; M-l up to A-34; M-l to A-33; M-1 to P-32; M-1 to R-31; M-1 to A-30; M-1 to P-29; M-1 to A-28; M-l to G-27; M-1 to R-26; M-l up to A-25; M-l to L-24; M-1 to P-23; M-l through L-22; M-l to L-21; M-l up to L-20; M-l through L-19; M-l through L-18; M-l through L-17; M-l to L-16; M-l up to L-15; M-l through L-14; M-l through F-13; M-1 to P-12; M-l to L-ll; M-l through W-10; M-1 to R-9; M-1 to P-8; M-l through A-7; of the SEC. ID NO: SEC. ID NO: 4. Preferably, any of the N- or C-terminal deletions listed above can be combined to produce a METH2 polypeptide with the N- and C-terminal e 1 -imino acids.

The invention also provides polypeptides having one or more amino acids removed from both amino and carboxyl terminals, which can be described generally as having residues m-n of SEC. ID NO: 2 or SEC. ID NO: 4, where n and m are integers as described above.

Also preferred is METH1 or METH2 polypeptide and fragments of the polynucleotide - characterized by the structural or functional domains. Preferred embodiments of the invention include fragments comprising alpha-helix and alpha-helix forming regions ("alpha regions"), beta-sheet and beta sheet-forming regions ("beta regions"), spin regions and spin-forming regions ("spin regions"), spiral regions and spiral-forming regions ("spiral regions"), hydrophilic regions , hydrophobic regions, antipathetic alpha regions, antipatic beta regions, flexible regions, surface forming regions, substrate binding regions, and regions of high antigenic index. As stated in the Figures, such preferred regions include the Garnier-Robson alpha regions, the beta regions, the spin regions, and the spiral regions, the 1 fa-Chou-Fasman regions, the beta regions, and the turning regions, the hydrophilic regions Ky te - Doo 1 i 111 e and the hydrophobic regions, the alpha Eisenberg regions and the unfriendly beta regions, the flexible regions Ka rp 1 us - S ch u z, the - surface forming regions Emini, and regions with high antigenic index Jameson-Wolf. The polypeptide fragments of SEC. ID NO: 2 falling within the conserved domains are specifically contemplated by the present invention. (See Figures 10 &11 and Tables 1 &2). In addition, fragments of the polynucleotide encoding these domains are also contemplated.

Other preferred fragments are the biologically active METH1 or METH2 fragments. The biologically active fragments are those that exhibit activity similar, but not necessarily identical, to an activity of the METH1 or METH2 polypeptide. The biological activity of the fragments may include an improved desired activity, or a decreased undesirable activity.

However, many polynucleotide sequences, such as EST sequences, are available and accessible to the public through the databases of the sequences. Some of these sequences - are related to the SEC. ID NO: 1 or SEC. ID NO: 3 and have been publicly available prior to the conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. Listing each related sequence would be an exceptional job. Accordingly, one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, wherein a is an integer from 1 to 936 of SEQ. Were preferably excluded from the present invention. ID NO: 1, b is an integer from 15 to 950; where both a and b correspond to the positions of the nucleotide residues shown in SEQ. ID NO: 1, and wherein b is greater than or equal to a + 14. In addition, one or more polynucleotides comprising a nucleotide sequence described by the general formula of ab, wherein a is any number are preferably excluded from the present invention. whole between 1 to 876 of the SEC. ID NO: 3, b is an integer from 15 to 890; where both a and b- correspond to the positions of the nucleotide residues shown in SEQ. ID NO: 3, and where b is greater than or equal to a + 14.

Epitopes and Antibodies In the present invention, "epitopes" refers to fragments of the METH1 or METH2 polypeptide having antigenic or immunogenic activity in an animal, especially a human, A preferred embodiment of the present invention relates to a fragment of the METH1 or METH2 polypeptide that comprises an epitope, as well as the polynucleotide that encodes this fragment A region of a protein molecule to which an antibody is linked is defined as an "antigenic epitope." In contrast, an "immunogenic epitope" is defined as a part of a protein that generates an antibody response (See, for example, Geysen et al., Proc. Natl. Acad. Sci. USA 81: 3998-4002 (1983)).

Fragments that work with normal -epitopes can be produced by any conventional means. (See, for example, Houghten, R.A., Proc. Natl. Acad. Sci. USA 82: 5131-5135 (1985) further described in U.S. Patent No. 4,631,211).

In the present invention, the antigenic epitopes preferably contain a sequence of at least seven, more preferably at least nine and even more preferably between about 15 to about 30 amino acids. Antigenic epitopes are useful for generating antibodies, including monoclonal antibodies, that specifically bind to the epitope. (See, for example, Wilson et al., Cell 37: 161-118 (1984); Sutcliffe, J. G. et al., Science 219: 660-666 (1983)).

Similarly, immunogenic epitopes can be used to induce antibodies according to methods well known in the art. (See, for example, Sutcliffe et al., Supra; Wilson et al., Supra; Chow, M. et al., Proc. Natl. Acad. - 53 -Sci. USA 82: 910-914; and Bittle, F. J. et al. , J. Gen. Virol. 66: 2341-2354 (1985)). A preferred immunogenic epitope includes the secreted protein. Immunogenic epitopes can be present together with a carrier protein, such as an albumin, to an animal system (such as a mouse or rabbit) or, if it is long enough (at least about 25 amino acids), without a carrier. However, immunogenic epitopes comprising as few as 8 to 10 amino acids have been shown to be sufficient to generate antibodies capable of binding to at least linear epitopes on a denatured polypeptide (e.g., spotting or Western blotting).

Using DNAstar analysis, it was found that SEC. ID NO: 2 is antigenic in amino acids: 2-14, 32-44, 47-60, 66-79, 87-103, 109-118, 146-162, 169-180, 183-219, 223-243, 275-284, 296-306, 314-334, 341-354, 357-376, 392-399, 401-410, 418-429, 438-454, 456-471, 474-488, 510-522, 524- 538, 550-561, 565-626, 630-643, 659-671, 679-721, -734-749, 784-804, 813-820, 825-832, 845-854, 860-894, 899- 917, 919-924 and 928-939. Thus, these regions could be used as epitopes to produce antibodies against the protein encoded by the METH1 cDNA.

Using DNAstar analysis, it was found that SEC. ID NO: 4 is antigenic in amino acids: 26-38, 45-52, 59-76, 80-99, 105-113, 129-136, 138-217, 254-263, 273-289, 294-313, 321-331, 339-356, 371-383, 417-427, 438-443, 459-471, 479-505, 507-526, 550-607, 615-640, 648-653, 660-667, 669- 681, 683-704, 717-732, 737-743, 775-787, 797-804, 811-825, 840-867 and 870-884. Thus, these regions could be used as epitopes to produce antibodies against the protein encoded by the METH2 cDNA.

As used here, the term "antibody" (Ab) or "monoclonal antibody" (MAb) means that it includes intact molecules as well as antibody fragments (such as, for example, the Fab and F (ab ') 2 fragments) which are capable of binding - specifically to the protein. The Fab and F (ab ') 2 fragments lack the Fc fragment of the intact antibody, and are more rapidly removed from the circulation, and may have a less non-specific binding to the tissue than an intact antibody. (Wahl et al., J. Nucí, Med. 24: 316-325 (1983)). Thus, these fragments are preferred, as well as the products of a FAB or other library of immunoglobulin expression. In addition, the antibodies of the present invention include chimeric, single chain, and humanized antibodies.

Fusion proteins Any METH1 or METH2 polypeptide can be used to generate the fusion proteins. For example, the METH1 or METH2 polypeptide, when fused to a second protein, can be used as an antigenic marker. The antibodies raised against the METH1 or METH2 polypeptide can be used to indirectly detect the second protein by binding to the -METH1 or METH2. In addition, because the target cellular locations of the secreted proteins are based on the traffic signals, the METH1 or METH2 polypeptides can be used as a target molecule once they are fused to other proteins.

Examples of domains that can be fused to the METH1 or METH2 polypeptides include not only heterologous signal sequences, but also other heterologous functional regions. The fusion does not necessarily need to be direct, but can occur through sequences * linkers.

In addition, the fusion proteins can also be generated by genetic engineering to improve the characteristics of the METH1 or METH2 polypeptide. For example, a region of the additional amino acids, particularly charged amino acids, can be added to the N-terminus of METH1 or METH2 polypeptide to improve stability and persistence during purification of the host cell or subsequent storage and handling. Also, portions of the peptide can be added to the METH1 or METH2 polypeptide to facilitate purification. Such regions can be removed prior to the final preparation of the METH1 or METH2 polypeptide. The adition of. Peptide portions facilitate the handling of the polypeptides and are routine and familiar techniques in the art.

In addition, METH1 or METH2 polypeptides, which include fragments, and specific epitopes, can be combined with parts of the immunoglobulins constant domain.

(IgG), which result in chimeric polypeptides.

These fusion proteins facilitate purification and show an increased half-life. One reported example describes chimeric proteins consisting of the first two domains of the human CD4 polypeptide and several domains of the heavy or light chain constant regions of mammalian immunoglobulins (EPA 394,827; Traunecker et al., Na ture - -331: 84-86 (1988)). Fusion proteins that have dimeric structures linked to the disulfide (due to IgG) may also be more efficient in binding and neutralizing other molecules than the secreted monomeric protein or the fragments of the proteins alone. (Fou n t ou 1 a k i s et al., J. Biochem 270: 3958-3964 (1995)).

Similarly, EP-A-0 464 533 (Canadian Counterpart 2045869) describes the fusion proteins comprising several portions of the constant region of the immunoglobulin molecules together with another human protein or part thereof. In many cases, the Fc part in a fusion protein is beneficial in therapy and diagnosis and can thus result, for example, in improved cooking properties (EP-A 0232 262). Alternatively, it would be desirable to remove the Fc part after the fusion protein has been expressed, detected and purified in the advantageous manner described. For example, the Fc portion can hide therapy and diagnosis, if the fusion protein is to be used as an antigen for immunizations. In drug discovery, for example, human proteins, such as hIL-5, have been fused with the Fc portions for the purpose of high throughput screening assays to identify hIL-5 antagonists. (See, D. Bennett et al., J. Mol. Recognition 8: 52-58 (1995); K. Johanson et al., J. of Biol. Chem. 270 (16): 9459-9471 (1995)) .

In addition, the METH1 or METH2 polypeptides can be fused to the marker sequences, such as a peptide that facilitates the purification of METH1 or METH2. In the preferred modalities, the marker amino acid sequence is a hexa-histidine peptide, such as the label provided in a pQE vector (QIAGEN, Inc., 9259 Eton Avenue, Chatsworth, CA, 91311), among others, many of which are commercially available. As described in Gentz et al. , Proc. Natl. Acad. Scí. USA 86: 821-824 (1989), for example, hexa-histidine provides convenient purification of the fusion protein. Another labeling peptide useful for purification, the "HA" identifier, corresponds to an epitope derived from the influenza hemagglutinin protein. (Wiíson et al., Ceil 37: 767 (1984)).

Thus, any of the above fusions can be generated by genetic engineering using the polynucleotides or the METH1 or METH2 polypeptides.

Biological Activities of METHl or METH2 The polynucleotides and METH1 or METH2 polypeptides can be used in assays to test one or more biological activities. If the METH1 or METH2 polynucleotides and polypeptides exhibit activity in a particular assay, it is likely that METH1 or METH2 is involved in conditions associated with biological activity. Therefore, METH1 or METH2 can be used to treat the associated condition.

- A c ti vi da d Inm u n e The METH1 or METH2 polynucleotides and polypeptides may be useful in treating deficiencies or disorders of the immune system, by activating or inhibiting the proliferation, differentiation, or mobilization (chemotaxis) of immune cells. Immune cells develop through a process called hema t opo i e s i s, which produces myeloids (platelets, red blood cells, neutrophils, and macrophages) and lymphoids (B and T lymphocytes) of pluripotent stem cells. The etiology of these deficiencies or immunological diseases can be genetic, somatic, such as cancer or some autoimmune diseases acquired (for example, by chemotherapy or toxins), or infectious. In addition, polynucleotides and METH1 or METH2 polypeptides can be used as a marker or detector of a particular immune system disorder or disorder.

The polynucleotides and METH1-α or METH2 polypeptides may be useful in treating or detecting deficiencies or conditions of the hematopoietic cells. Polynucleotides and METH1 or METH2 polypeptides could be used to increase the differentiation and proliferation of hematopoietic cells, including pluripotent stem cells, in an effort to treat those conditions associated with a decrease in certain (or many) cell types. hematopoietic Examples of immune deficiency syndromes include, but are not limited to: blood protein disorders (eg agammagl obu 1 i nemi a, dis gammagl obu 1 inemi), telangiectasia ataxia, common variable immunodeficiency, Digeorge syndrome , HIV infection, HTLV-BLV infection, leukocyte adhesion deficiency syndrome, lymphopenia, phagocytic bactericidal dysfunction, severe combined immunodeficiency (SCIDs), Wi s ko tt disease - Aldr i ch, anemia, thrombocytopenia, oh emo g 1 ob i nu ria.

In addition, METH1 or METH2 polynucleotides and polypeptides can also be used to modulate hemostatic activity (the arrest of bleeding) or thrombolytic activity (clot formation). For example, increased hemostatic or thrombolytic activity, polynucleotides and METH1 or METH2 polypeptides can be used to treat blood coagulation conditions (eg, af ibr in ogenemi a, factor deficiencies), blood platelet disorders ( for example thrombocytopenia), or injuries resulting from trauma, surgery, or other causes. Alternatively, METH1 or METH2 polynucleotides and polypeptides that can decrease hemostatic or thrombolytic activity can be used to inhibit or dissolve clots, important in the treatment of heart attacks (infarction), stroke or wound healing.

The polynucleotides and polypeptides METHl or METH2 may also be useful in the treatment or detection of autoimmune diseases. Many autoimmune disorders - 4 are the result of inappropriate recognition of themselves or foreign materials by immune cells. This inappropriate recognition results in an immune response that leads to the destruction of the host or host tissue. Therefore, the administration of polynucleotides and METH1 or METH2 polypeptides that can inhibit an immune response, in particular the proliferation, differentiation, or chemotaxis of T cells, can be an effective therapy in the prevention of autoimmune diseases.

Examples of autoimmune conditions that can be treated or detected by METH1 or METH2 include, but are not limited to: Addison's disease, hemolytic anemia, anti-ifospholipid syndrome, rheumatoid arthritis, dermatitis, encephalomyelitis is allergic, glomerulonephritis, Goodpasture, Graves' Disease, Multiple Sclerosis, Gravis Myasthenia, Neuritis, Ophthalmia, Bullous Fenfigoide, Pemphigus, Polyendocr i nopaties, Purpura, - Reiter's Disease, Stiff-Man Syndrome, Autoimmune Thyroiditis, Systemic Lupus Erythematosus, Pulmonary Inflammation Autoimmune, Guillain-Barre syndrome, diabetes mellitus dependent on insulin, and inflammatory, autoimmune eye disease.

Similarly, allergic reactions and conditions, such as asthma (particularly allergic asthma) or other respiratory problems, can also be treated by polynucleotides and METH1 or METH2 polypeptides. In addition, METH1 or METH2 can be used to treat anaphylaxis, hypersensitivity to an antigenic molecule, or incompatibility of blood groups The polynucleotides and METH1 or METH2 polypeptides are also useful for treating and / or preventing rejection of organs or the disease in a chronic or non-hostile condition (GVHD). The rejection of the organs occurs due to the immune cellular destruction of the host of the transplanted tissue through an immune response. Similarly, an immune response is also involved in GVHD, but, in this case, the transplanted foreign immune cells destroy the host tissues. The administration of polynucleotides and METH1 or METH2 polypeptides that inhibit an immune response, particularly the proliferation, differentiation, or chemotaxis of T cells, can be an effective therapy in preventing rejection of organs or GVHD.

Similarly, polynucleotide and METH1 or METH2 polypeptides can also be used to modulate inflammation. For example, polynucleotides and METH1 or METH2 polypeptides can inhibit the proliferation and differentiation of cells involved in an inflammatory response. These molecules can be used to treat inflammatory conditions, both chronic and acute conditions, which include inflammation associated with infections (for example, septic shock, sepsis, or systemic inflammatory response syndrome (SIRS)), - damage caused by reper if there is still a case, endotoxin lethality, arthritis, complement-mediated hyperacute rejection, nephritis, cytokine-induced or chemokine-induced lung damage, inflammatory bowel disease, Crohn's disease, or the result of overproduction of cytokines ( for example, TNF or IL-1).

Pa d e cimi en t o s Hip erp ro l i f ti ti s The polynucleotides and METH1 or METH2 polypeptides can be used to treat or detect hyperproliferative disorders, including neoplasms, the polynucleotides and METH1 or METH2 polypeptides can inhibit the oliferation of the condition through interactions or indirect. Alternatively, polynucleotides and METH1 or METH2 polypeptides can proliferate other cells that can inhibit the iterative hyperprol condition.

For example, by increasing an immune response, particularly by increasing the antigenic qualities of the hyperproliferative condition or by proliferation, differentiation, or mobilization of T cells, hyperproliferative conditions can be treated. This immune response can be increased by either improving an existing immune response, or initiating a new immune response. Alternatively, decreasing an immune response may also be a method for treating hyperproliferative conditions, such as a chemotherapeutic agent.

Examples of hyperproliferative conditions that can be treated or detected by METH1 or METH2 polynucleotides and polypeptides include, but are not limited to, neoplasms located in: abdomen, bone, breast, digestive system, liver, pancreas, peritoneum, endocrine glands (adrenal) , parathyroid, pituitary, testes, ovaries, thymus, thyroid), eyes, head and neck, nervous system (central and peripheral), lymphatic system, pelvis, skin, soft tissue, spleen, thoracic system, and -urogenital Similarly, other hyperproliferative conditions can also be treated or detected by the poly i, nucleotide and METH1 or METH2 polypeptides. The p-axis of such hyperproliferative disorders include, but are not limited to: hypergammaglobulinemia, lymphoid conditions, paraproinemia, purpura, sarcoidosis, Sezary's Syndrome, Waldenstron's Macroglobulinemia, Gaucher's Disease, histo cysts, and other hyperproliferative diseases, in addition to neoplasia, located in an organic system listed above.

Infectious diseases The METH1 or METH2 polynucleotides or polypeptides can be used to treat or detect infectious agents. For example, by increasing the immune response, particularly increasing the proliferation and differentiation of B and / or T cells, infectious diseases can be treated - thus. The immune response can be increased by improving an existing immune response, or initiating a new immune response. Alternatively, polynucleotide or METH1 or METH2 polypeptides can also directly inhibit the infectious agent, without the need to generate an immune response.

Viruses are an example of an infectious agent that can cause conditions or symptoms that can be treated or detected by polynucleotides or METH1 or METH2 polypeptides. Examples of viruses, include but are not limited to the following viral or RNA viral families: Arboviruses, Aden ovi ri da e, Ar en a vi ri dae, Arterivirus, Birnaviridae, Buny a vi ri dae, Ca 1 ci vi ri Da e, C ir co vi da da, Cor ona vi ri dae, Fl a vi vi ri dae, H ep ad av av a (Hepatitis), He rpes vi ri dae (such as, Cytomegalovirus, Herpes Simplex, Herpes Zoster), Mononegavi rus (for example, Parami xovi r idae, Morbi 11 i vi rus, Rhabdovi ridae), Ort omixovi ridae (for example, Influenza), P a va vi ri da e, P a rvo vi ri da , - -Pi cornaviridae, Poxviridae (such as Smallpox or Vaccinia), Reoviridae (for example, Rotavirus), Retroviridae (HTLV-I, HTLV-II, Lentivirus), and Togaviridae (for example, Rubivirus). Viruses that fall within these families can cause a variety of conditions or symptoms, including, but not limited to, bronchitis, encephalitis, eye infections (eg, conjunctivitis, keratitis), chronic fatigue syndrome , hepatitis (A, B, C, E, Chronic Active, Delta), meningitis, infections opo rtunisti ca s (for example, AIDS), pneumonia, 'Burkitt lymphoma, chicken pox, hemorrhagic fever, Measles, Mumps, Parainfluenza, Rabies , common cold, polio, leukemia, rubella, sexually transmitted diseases, skin conditions (for example, Kaposi, warts), and viremia. The polynucleotides or METH1 or METH2 polypeptides can be used to treat or detect any of these symptoms or conditions.

In an immanent manner, the bacterial or fungal agents which can cause conditions or symptoms and which can be treated or detected by the METH1 or METH2 polynucleotides or polypeptides include, but are not limited to, the following bacterial families and fungi. Gram-positive and negative: Ac ti nomy ce t al es (for example, Corynebacterium, Mycobacterium, Norcadia), Asp egi 11 osis, Bacillaceae (for example, Anthrax, Clostridium), Bac te roidaceae, Blas tomycosis, Bordetella, Borrelia, Brucellosis, Candidiasis, Campylobacter, Coccidioidomycosis, Cryptococcosis, Dermatocycosis, Enterobacteriaceae (Klebsiella, Salmonella, Serratia, Yersinia), Erysipelothr ix, Helicobacter, L egi on e 11 osis, Lep tospirosis, Listeria, My c op 1 a sma ta 1 is, Neisseria ce ae (for example, Acinetobacter, Gonorrhea, Me ni ngococo), Infections of Pa st eur e 11 a cea (for example, Actinobacillus, Haemophilus, Pasteurella), Pseudomonas , Ri c ke 11 s i a ce ae, Ch 1 amyd i a ce ae, Syphilis, and Staphylococci. These families of bacteria or fungi can cause the following conditions or symptoms, including but not limited to: bacteremia, endocarditis, - -infections of the eyes (conjunctivitis, tuberculosis, uveitis), gingivitis, opportunistic infections (for example , infections related to AIDS), paronychia, prosthesis-related infections, Reiter's disease, respiratory tract infections, such as Whooping cough or emphysema, sepsis, Lyme disease, Cat-Scratch disease, dysentery, fever oidea, food poisoning, typhoid, pneumonia, gonorrhea, meningitis, chlamydia, syphilis, diphtheria, leprosy, para t uber cu losi s, tuberculosis, lupus, botulism, gangrene, tetanus, impetigo, rheumatic fever, scarlet fever, sexually transmitted diseases , skin conditions (eg, cellulitis, der at oc i eos is), toxemia, urinary tract infections, wound infections, polynucleotide or METH1 or METH2 polypeptides can be used to treat or detect any of these symptoms or conditions.

In addition, parasitic agents that cause conditions or symptoms that can be treated or detected by polynucleotides or METH1 or METH2 polypeptides include, but are not limited to, the following families: Amebiasis, Babesiosis, Coccidiosis, Cryptosporidiosis, Dientamoebiasis, Dourina, Ec T opa ras ti ti co, Giardiasis, He lminan ti as is, Leishmaniasis, Theileriasis, Toxoplasmosis, Trypanosomiasis, and Trichomonas. These parasites can cause a variety of conditions or symptoms, including, but not limited to: scabies, thrombiculiasis, eye infections, intestinal conditions (eg, dysentery, giardiasis), liver diseases, lung diseases, infections opo rt a sti ca s (for example, related to AIDS), Malaria, complications of pregnancy, and toxoplasmosis, polynucleotides or METHl or METH2 polypeptides can be used to treat or detect any of these symptoms or conditions.

Preferably, the treatment using the METH1 or METH2 polynucleotides or polypeptides could be either - by administering an effective amount of the METH1 or METH2 polypeptide to the patient, or by removing the patient's cells, supplying the cells with the METH1 or METH2 polypeptide, and returning to . generate the cells by genetic engineering to the patient (ex vivo therapy). In addition, polynucleotides or METH1 or METH2 polypeptides can be used as an antigen in a vaccine to generate an immune response against infectious diseases.

Regeneration The polynucleotides or polypeptides METHl or METH2 can be used to differentiate, proliferate, and attract cells, leading to the regeneration of tissues.

(See, Science 276: 59-81 (1997)). Tissue regeneration could be used to repair, replace, or protect damaged tissue due to congenital defects, trauma (wounds, burns, incisions, or ulcers), for aging, conditions (for example, osteoporosis, osteoarthritis, conditions -periodontal, liver failure), surgery, which includes cosmetic plastic surgery, fibrosis, reperfusion injury, or damage by systemic cytokine.

The tissues that could be regenerated using the present invention include organs (eg, pancreas, liver, intestine, kidney, skin, endothelium), muscles (smooth, skeletal or cardiac), vascular (including vascular endothelium), nervous tissue , hematopoietic, and skeletal (bones, cartilages, tendons, and ligaments). Preferably, the regeneration is carried out without or with a reduced generation of scars. Regeneration may also include angiogenesis.

In addition, polynucleotides or METH1 or METH2 polypeptides can increase the regeneration of difficult-to-heal tissues. For example, the increased regeneration of the s and 1 i gamen t or s could be recovered quickly after a time of damage. The polynucleotides or METH1 or METH2 polypeptides of the present invention could also be used prophylactically in an effort to avoid damage. Specific conditions that could be treated include tendonitis, carpal tunnel syndrome, and other tendon or ligament defects. A further example of the regeneration of non-healing wound tissues include pressure ulcers, ulcers associated with vascular insufficiency, surgical or traumatic wounds.

Similarly, nerve and brain tissues can also be regenerated using polynucleotides or METH1 or METH2 polypeptides to proliferate and differentiate nerve cells. Conditions that can be treated using this method include central and peripheral nervous system conditions, neuropathies, or mechanical and traumatic conditions (eg, spinal cord disease, head trauma, cerebrovascular disease, and diseases by filling). Specifically, - the conditions associated with peripheral nerve damage, peripheral neuropathy (for example, resulting from chemotherapies or other medical therapies), localized neuropathies, and central nervous system disorders (for example, Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, and Shy-Drager's syndrome), all could be treated using polynucleotides or METH1 or METH2 polypeptides.

Q u i m i o t a x i s The polynucleotides or METH1 or METH2 polypeptides may have chemotaxis activity. A chemotactic molecule attracts or mobilizes cells (e.g., monocytes, fibroblasts, neutrophils, T cells, mast cells, eosinophils, epithelial and / or endothelial cells) to a particular site in the body, such as inflammation, infection, or site. of h ipe rpr o 1 if er ac ion. The mobilized cells can then fight and / or cure the particular traumas or abnormalities The polynucleotides or polypeptides METH1 or METH2 can increase the chemotactic activity of particular cells. These chemo taxi molecules can then be used to treat inflammation, infection, hyperproliferative disorders, or any condition of the immune system by increasing the number of target cells to a particular location in the body. For example, cells that can be used to treat wounds and other traumas to tissues by attracting immune cells to the damaged location. As a chemotactic molecule, METH1 or METH2 could also attract fibroblasts, which can be used to treat wounds.

It is also contemplated that polynucleotides or METH1 or METH2 polypeptides can inhibit chemotactic activity. These molecules could be used to treat the conditions. Thus, polynucleotides or METH1 or METH2 polypeptides could be used as inhibitors of chemotaxis.

Binding Activity or Linker METH1 or METH2 polypeptides can be used to select molecules that bind to METH1 or METH2 or to molecules for which METH1 or METH2 bind. The binding of METH1 or METH2 and the molecule can activate (agonist), increase, inhibit (antagonist), or decrease the activity of METH1 or METH2 or the bound molecule. Examples of such molecules include antibodies, oligonucleotides, proteins (e.g., receptors), or molecules that are not.

Preferably, the molecule is very closely related to the natural ligand of METH1 or METH2, for example, a fragment of the ligand, or a natural substrate, a ligand, a functional or structural mimetic. (See, Coligan et al., Current Protocols in Immunolgy 1 (2) Chapter 5 (1991)). Similarly, the molecule can be closely related to the natural receptor to which METH1 or METH2 binds, or at least to a fragment of the receptor capable of being linked by METH1 or METH2 (eg, an active site). In any case, the molecule can be designed rationally using the techniques known.

Preferably, the selection of these molecules involves the production of appropriate cells that express METH1 or METH2, either as a secreted protein or in the cell membrane. Preferred cells include mammalian cells, yeast, Drosophila, or E. c or l i. Cells expressing METH1 or METH2 (or cell membranes containing the expressed polypeptide) are preferably contacted with a test compound that potentially contains the molecule to observe binding, stimulation, or inhibition of the activity of either METH1. or METH2 or the molecule.

The test can simply test the binding or agglutination of a candidate compound to METH1 or METH2, where the binding is detected by a label, or in an assay involving competition with a labeled competitor. In addition, the assay can test whether the candidate compound results in a signal generated by the METH1 or METH2 link.

Alternatively, the assay can be carried out using cell-free preparations, po 1 ipép t i do / mo 1 é cu 1 a fixed to a solid support, chemical libraries or mixtures of natural products. The assay may also simply comprise the steps of mixing a candidate compound with a solution containing METH1 or METH2, measuring the activity or bonding of METH1 or METH2 / mo or 1cu1 a, and comparing the activity or binding of METH1 or METH 2 / mo 1 é cu 1 a with a standard.

Preferably, an ELISA assay can measure the level or activity of METH1 or METH2 - in a sample (eg, biological sample) using a monoclonal or polyclonal antibody. The antibody can measure the level or activity of METH1 or METH2 by either directly or indirectly binding to METH1 or METH2 or by competing with METH1 or METH2 for a substrate.

All previous trials can be used as diagnostic or prognostic markers. The molecules discovered using these assays can be used to treat the condition or to generate a particular result in a patient (e.g., the growth of blood vessels) by activating or inhibiting the METH1 or METH2 molecule.

In addition, the assays can discover the agents that can inhibit or enhance the production of METH1 or METH2 from properly manipulated cells or tissues.

Therefore, the invention includes a method for identifying compounds that bind to METH1 or METH2 comprising the steps of: (a) incubating a candidate binding compound with METH1 or METH2; and (b) determine if the link or agglutination has occurred. In addition, the invention includes a method for identifying agonists or anabolisms comprising the steps of: (a) incubating a candidate compound with METH1 or METH2, (b) assaying a biological activity, and (b) determining if a biological activity of METH1 or METH2 has been altered.

Other activities The METH1 or METH2 polynucleotides or polypeptides can also increase or decrease the differentiation or rolling of embryonic stem cells, in addition, as discussed above, the hematopoietic lineage.

Polynucleotides or METH1 or METH2 polypeptides can also be used to modulate the characteristics of mammals, such as body height, weight, hair color, eye color, skin, adipose tissue percentage, pigmentation, size and shape (for example, cosmetic surgery). Similarly, METH1 or METH2 polynucleotides or polypeptides can be used to modulate the metabolism of mammals that affect catabolism, anabolism, processing, utilization, and energy storage.

The polynucleotides or polypeptides METHl or METH2 can be used to change a mental state or physical state of a mammal by influencing biorhythms, circadian rhythms, depression (including depressive illness), the tendency to violence, tolerance to pain, reproductive capacities ( preferably pro Activin or activity similar to Inhibin), hormonal or endocrine levels, appetite, libido, memory, tension, or other cognitive qualities.

The METH1 or METH2 polynucleotide or polypeptides can also be used - as an additive or food preservative, such as to increase or decrease the storage capacities, the content of fat, lipids, proteins, carbohydrates, vitamins, minerals, cofactors or other nutritional components.

Having generally described the invention, it will be easier to understand with reference to the following examples, which are provided by way of illustration and are not intended to be limiting.

Diagnosis and Cancer Forecast It is believed that certain tissues in mammals with cancer express significantly decreased levels of the METH1 or METH2 protein and the mRNA encoding the METH1 or METH2 protein when compared to a corresponding mammalian "pattern," ie, a mammal of the same species. that does not have cancer. In addition, it is believed that decreased levels of the METH1 or METH2 protein may be detected in certain body fluids (eg, serum, plasma, urine, and spinal fluid) of mammals with cancer when compared to the serum of the animals. mammals of the same species that does not have cancer. Thus, the invention provides a useful diagnostic method during the diagnosis of tumors, which involves testing the level of expression of the gene encoding the METH1 protein in mammalian cells or in body fluids and comparing the level of expression of the gene with a level of expression of the standard METH1 gene, so a decrease in the level of expression of the gene under the standard or standard is indicative of certain tumors. The invention also provides a diagnostic method useful during the diagnosis of tumors, which involves testing the level of expression of the gene encoding METH2 protein in mammalian cells or body fluids and comparing the expression level of the gene with a level of expression of the standard METH2 gene, so that a decrease in the level of expression of the gene - under the standard or pattern is indicative of certain tumors.

Where the diagnosis of a tumor has been carried out according to conventional methods, the present invention is useful as an indicator of prognosis, so that patients exhibiting a diminished expression of METH1 or METH2 will experience a worse clinical behavior in relation to to patients who express the gene at a lower level.

By "assay of the level of expression of the gene encoding the protein METHl or METH2"is indicated to measure qualitatively or quantitatively or estimate the level of the METH1 or METH2 protein or the level of mRNA encoding the METH1 or METH2 protein in a first biological sample either directly (for example, by determining or estimating the level of absolute protein or mRNA level) or relatively (for example, comparing the level of the METH1 or METH2 protein or the level of mRNA in a second-biological sample) Preferably, the level of the METH1 or METH2 protein or the level of mRNA in the first biological sample is measured or estimated and compared to a standard level of the METH1 or METH2 protein or mRNA level, the standard is taken from a second biological sample obtained from an individual who does not have cancer. As will be appreciated in the art, once the standard or standard level of the METH1 or METH2 protein or mRNA level is known, it can be used repeatedly as a standard or standard for comparison.

By "biological sample" it is indicated that any biological sample obtained from an individual, cell line, tissue culture, or other source containing the METH1 or METH2 protein or the mRNA. Biological samples include the body fluids of mammals (such as serum, plasma, urine, synovial fluid, and spinal fluid) that contain the mature METH2 or METH2 protein, secreted, and the adrenal, thyroid, stomach, and brain tissues. the heart, the placenta, the lungs, liver, muscles, kidneys, pancreas, testes and ovaries (for METHl); and the tissues of the prostate, small intestine, colon, brain and lung (for METH2).

The present invention is useful for detecting cancer in mammals. In particular, the invention is useful during the diagnosis of the following types of cancers in mammals: breast, ovarian, prostate, liver, lung, pancreatic, colon, and testicular. Preferred mammals include monkeys, apes, cats, dogs, cows, pigs, horses, rabbits and humans. Human are particularly preferred.

Total cellular RNA can be isolated from a biological sample using the one-step method of guanidinium-t i or c a an t o-f e n o 1-c 1 or r o f or rmo described in Chomczynski and Sacchi, An a l. B i or ch em. 152: 156-159 (1997). The mRNA levels which encode the METH1 or METH2 protein are then assayed using any appropriate method. These include analysis by staining or Northern blotting (Harada et al., Cell 53: 303-312 (1990)). The formation of the nuclease map SI (Fujita et al., Cell 49: 351-361 (1987)), the polymerase chain reaction (PCR), the reverse transcription in combination with the chain reaction of the polymerase (RTPCR) (Makino et al., Technique 2: 295-301 (1990)), reverse transcription in combination with the ligase chain reaction (RT-LCR).

Testing the levels of the METH1 or METH2 protein in a biological sample can occur using the antibody-based techniques. For example, the expression of METH1 or METH2 protein in tissues can be studied with classical immunohistochemical methods (Jalkanen, M., et al., J. Cell, Biol. 101: 976-985 (1985)). Jalkanen, M., et al., J. Cell, Biol. 105: 3087-3096 (1987)).

- - Other antimicrobial-based methods useful for detecting the expression of the METH1 or METH2 protein gene include immunoassays, such as enzyme linked immunosorbent assay (ELISA) and radioimmunoassays (RIA).

Suitable labels are known in the art and include enzymes, such as glucose oxidase, and radioisotopes, such as iodine (125 I, 121 I), carbon (14 C), sulfur (35 S), tritium (3 H), indium (1 I), In), and technetium (mTc), and 'fluorescent labels such as fluorescein and rhodamine, and biotin.

Administration modes It is recognized that an increase in vascular supply plays a central role in the progress and metastasis of the tumor; therefore, angiogenesis inhibitors may prove to be effective as an adjuvant therapy for patients with cancer.

- Some of the angiogenic suppressors recognized herein are poor candidates for systemic treatment due to severe side effects. The present inventors have found that METH1 and METH2 are potent inhibitors of angiogenesis both in vivo and in vivo. The advantage of METH1 and METH2 is that these inhibitors are normally associated with the suppression of physiological angiogenesis; therefore, they offer a lack of toxicity and endothelial specificity over angiogenic inhibitors. In addition, METH1 and METH2 present a restricted pattern of expression that provides a possible advantage in the 'organic specificity.

Accordingly, the polypeptides of the present invention can be used to treat cancer. The METH1 and METH2 polypeptides of the present invention can also be used to "treat individuals with other conditions that are related to the angiogenesis, which include the healing of the anus inflammation 1, rheumatoid arthritis. , psoriasis, endometrial bleeding disorders, diabetic retinopathy, some forms of macular degeneration, hemangiomas, and arterial-venous malformations.

Thus, the invention provides a method for inhibiting angiogenesis in an individual comprising administering to such an individual a pharmaceutical composition comprising an effective amount of an isolated METH1 polypeptide of the invention, effective to increase the level of METH1 activity in such an individual. The invention also provides a method for inhibiting angiogenesis in an individual comprising administering to such an individual a pharmaceutical composition comprising an effective amount of an isolated METH2 polypeptide of the invention, effective to increase the level of activity in such an individual.

METH1 polypeptides that can be used to inhibit angiogenesis in this manner include: the METH1 polypeptide encoded by the deposited cDNA including the leader; the mature METH1 polypeptide encoded by the deposited cDNA minus the leader (i.e., the mature protein); a polypeptide comprising amino acids from about 1 to about 950 in SEQ. ID NO: 2, a polypeptide comprising amino acids from about 2 to about 950 in SEQ. ID NO: 2, a polypeptide comprising amino acids from about 29 to about 950 in SEQ. ID NO: 2; a polypeptide comprising amino acids from about 30 to about 950 in SEQ. ID NO: 2, a polypeptide comprising the metalloprotease domain of METH1, amino acids 235 to 459 in SEQ. ID NO. 2; a polypeptide comprising the disintegrin domain of METH1, amino acids 460 to 544 in SEQ. ID NO. 2; a polypeptide comprising the first domain similar to the TSP of METH1, amino acids 545 to 598 in SEQ. ID NO. 2; a polypeptide comprising the second domain similar to the TSP of METH1, amino acids 841 to 894 in SEQ. ID NO. 2; a polypeptide comprising the third domain similar to the TSP of METH1, amino acids 895 to 934 in SEQ. ID NO. 2; a polypeptide comprising amino acids 536 to 613 in the SEC. ID NO. 2; and a polypeptide comprising amino acids 549 to 563 in SEQ. ID NO. 2.

METH2 polypeptides that can be used to inhibit angiogenesis in this manner include: the METH2 polypeptide encoded by the deposited cDNA that includes the leader; the mature METH2 polypeptide encoded by the deposited cDNA minus the leader (i.e., the mature protein); a polypeptide comprising amino acids from about 1 to about 890 in SEQ. ID NO: 4, a polypeptide comprising amino acids from about 2 to about 890 in SEQ. ID NO: 4, a polypeptide comprising amino acids from about -24 to about 890 in SEQ. ID NO: 4, a polypeptide comprising amino acids from about 112 to about 890 in SEQ. ID NO: 4, a polypeptide comprising the metalloprotease domain of METH2, amino acids 214 to 439 in SEQ. ID NO. 4; a polypeptide comprising the disintegrin domain of METH2, amino acids 440 through 529 in SEQ. ID NO. 4; a polypeptide comprising the first TSP-like domain of METH2, amino acids 530 to 583 in SEQ. ID NO. 4; a polypeptide comprising the second domain similar to the TSP of METH2, amino acids 837 to 890 in SEQ. ID NO. 4; a polypeptide comprising amino acids 280 to 606 in SEQ. ID NO. 4; and a polypeptide comprising amino acids 529 to 548 in SEQ. ID NO. Four.

As a general proposal, the total pharmaceutically effective amount of the METH1 or METH2 polypeptide administered parenterally per dose will be in the range of about 1 μg / kg / day to 10 μg / kg / day per body weight of the patient, although, as noted above, this will be subject to therapeutic discretion. More preferably, this dose is at least 0.01 μg / kg / day, and more preferably for humans between about 0.01 and 1 μg / kg / day for the polypeptide. If given continuously, the METH1 or METH2 polypeptide is typically administered at a dosage rate of about 1 μg / kg / hour to about 50 μg / kg / hour, either by 1-4 injections per day or by continuous subcutaneous infusions, for example, using a mini-pump. A solution for an intravenous bag can also be used.

The pharmaceutical compositions containing the METH1 or METH2 of the invention can be administered orally, rectally, parenterally, intracystemically, intravaginally, intraperitoneally, topically (as powders, ointments, drops or transdermal patches), buccally, or as an oral or nasal spray. . By "pharmaceutically acceptable carrier" is meant a solid, semi-solid or liquid, non-toxic filler, diluent, encapsulating material or auxiliary formulation of any kind. The term "parenteral" as used herein refers to modes of administration that include intravenous, intramuscular, intraperitoneal, i n t r a s t e r n a 1, subcutaneous injection and infusion and infusion.

In sa s s chromos o um i c o s The nucleic acid molecules of the present invention are also valuable for the identification of chromosomes. The sequence becomes a specific target and can hybridize to a particular location on an individual human chromosome. The formation of the correlation or map of the DNA with respect to the chromosomes according to the present invention is a first important step in the correlation of those sequences with the genes associated with the conditions.

- - In certain preferred embodiments in connection therewith, the cDNA described herein is used to clone the genomic DNA of a METH1 or METH2 protein gene. This can be complemented using a variety of well-known techniques and libraries, which are usually commercially available. Genomic DNA is then used for the formation of chromosomal maps i n s i t u using techniques well known for this purpose.

In addition, in some cases, the sequences can be correlated to chromosomes by preparing PCR primers (preferably 15-25 bp) of the cDNA. Computer analysis of the 3 'untranslated region of the gene is used to quickly select primers that do not generate a space of more than one exon in the Genomic DNA, thus complicating the amplification process. These primers are then used for the selection of PCR from somatic cell hybrids containing - individual human chromosomes Fluorescence in situ hybridization ("FISH") from a cDNA clone to a metaphase chromosomal extension can be used to provide precise chromosomal location in one step. This technique can be used with probes from the cDNA as short as 50 or 60 bp. For a review of this technique, see Verma et al. , Human Chromosomes: A Manual of Basic T echnique, Pergamon Press, New Yor (1988).

Once a sequence has been correlated to an accurate chromosomal location, the physical position of the sequence on the chromosome can be correlated with the genetic map data. Such data are found, for example, in V. McKusick, Mandelian Inheritance In Man, available online through the Johns Hopkins University, Welch Medical Library. The relationship between genes and disorders? Pu e have been correlated for the same -chromosomal region are then identified through linkage analysis (coherence of physically adjacent genes).

Next, if necessary, determine the differences in the cDNA or in the genomic sequence between affected and unaffected individuals. If a mutation is observed in some or all affected individuals but not in any normal individual, then the mutation is considered a causative agent of the condition.

Having generally described the invention, it will be more easily made by reference to the following examples, which are provided by way of illustration and do not intend to be imitated.

- Ex emp ls Ej empl o Identification and cloning of METHl and METH 2 To investigate novel genes with TSP-like domains, a large human cDNA data base consisting of approximately 900,000 expressed sequence tags (EST) was selected for sequences homologous to the second type I repeat of TSP1. Several ESTs were predicted for the proteins encoded with the TSP-like domains. Two cDNA clones were originated from the heart and lung libraries of human and which were sequenced and chosen for functional analysis.

The amino-terminal end of METH1 was obtained using a fast 5 'amplification of the cDNA ends (RACE) by the PCR technique (Marathon cDNA amplification, Clontech) according to the manufacturer's instructions. The amino-terminal end of METH2 was partially obtained through the 5-RACE-PCR and subsequently confirmed and completed by genomic selection. For genomic selection, the BAC clones (Genome Systems) were initially identified PCR. Positive BAC clones containing 150-200 bp of sequence were subsequently subclanded in the pGEM vector as small fragments and sequenced.

The analysis and comparison of the deduced amino acid sequence with the databases of GenBank, EMBL and SwissProt suggested that these genes belonged to a new family of metalloproteases with homology to the reprolysin family at its terminal NH2 end and with several motifs similar to TSP at the COOH end. These cDNAs were named METHl and METH2, ME, for the metalloprotease and TH, for the t romb or sp or nd i n a. The mouse homolog of METH1 was identified and named ADAMTS1 (Kuno, K., et al., J.B.C., 272: 556-562 (1997)). Direct comparison of the human and mouse sequences revealed a high level of preservation (83.4% of the amino acid identity). Thus no homologs were identified for METH2.

Interestingly, a newly identified protein named pNPl (Procollagen N-proteinase I (Colidge, A., et al., Proc. Natl. Acad. Sci. USA 94: 2314-2379 (1997)) showed a sequence and structures very similar to METHl and METH2 (Figure 3). According to the new proteins described here, pNPl also contains the metallo roteinasa (subfamily of reprolysin) and the TSP domains at the carboxy terminal end. Although the sequence for pNP1 is of bovine origin, the sequence alignment revealed identical structure characteristics. The amino acid similarity between METH1 and METH2 is 51.7% and between METH1 or METH2 and pNP1 the homology is less than 33.9% and 36.3%, respectively.

Sequence analysis showed that the ORF of METH1 and METH2 encoded for the 950 and 890 amino acid proteins, respectively. In all three proteins, the terminal H2 terminus contained a putative signal peptide followed by another putative transmembrane domain around amino acid 300, deduced from the hydrophilicity plots. It is not clear if these proteins are linked to the transmembrane. However, according to the preliminary data given, it is more feasible that this second transmembrane domain consists of a hydrophobic package and that METH1, METH2 and pNP1 are in fact secreted proteins. The NH2-terminal end passes the signal peptide and has homology to the zinc metalloprotease superfamily and can be subdivided into a prodomain, a metalloprotease domain, and a cysteine-rich region.

The secu ency with double underlining in METH1 and METH2 in Figure 3 located at the boundaries between the prodomain and the metalloprotease domain are potential cleavage sites for mammalian subtilisins, such as furins (Barr, 1991).

The proteolytic process occurs in the SVMP to generate soluble metalloproteases and di s in t egr i na s (Bjarnason, JB &Fox, JW, Methods Enzymol 248: 345-368 (1995)) and has also been detected in some ADAM (reviewed by Wolsberg, TG &White, JM, Developmental Biology 180: 389-401 (1996)). At this point, preliminary experiments suggest that the proteolytic procedure occurs, at least in METH1. Additionally, both METH1 and METH2 present a Zn2 + binding site (dotted lines in Figure 3) that is presumed to be catalytically active due to the conservation of certain functionally important amino acids (Rawlings, N.D. &Barrett, A.J., Methods Enzymol. 248: 183-228 (1995)) suggesting that these proteins may be active proteases. Following the domain of the metalloprotease, there is a cysteine-rich region containing two putative disintegrin circuits (Wolsberg, TG &White, JM "., Developmental Biology 180: 389-401 (1996)) (marked with arrows in the Figure 3) Dysintegrin domains within the superfamily of metalloproteases in the snake venom metalloproteases (SVMP) and ADAM (mammalian proteins containing a disintegrin domain and a metalloprotease domain) and have a possible function were found. of inhibiting the binding of the integrins to their ligands in SVMP In the opposite way, the domain similar to the disintegrin ADAM, as part of the proteins anchored to the membrane can promote better than the break, the interactions cé 1 u 1 a - cé lu 1 a (Wolsberg, T.G. &White, J.M., Developmental Biology 180: 389-401 (1996)). The TSP-like domains are located in the COOH moiety of the METH1 and METH2 proteins. The METH1 contains two conserved TSP domains, separated by a spacer region with an unknown function, and a subdominium with a lower homology, and only 5 cysteines, following the second an γ-angiogenic region. METH2 contains two TSP domains separated by the spacer region. The alignment of the TSP-like domains of METH1 and METH2 with those of TSP1 and TSP2 are shown in Figure 5. The homology varies between 19.2% to 52% of amino acid similarity among all TSP repeats. The cysteines, numbered from 1 to 6, and the tryptophan, labeled by asterisks, are highly conserved.

Spotting or Southern blotting of human genomic DNA revealed the presence of METH1 and METH2 in the genome. The METH1 and METH2 probes revealed bands of different sizes suggesting that they are transcribed from different genes.

The consensus sequence for type I repeats includes 16 residues with 6 perfectly conserved cysteines. It typically begins with the sequence motif WSXWS (SEQ ID NO: 82) which has also been shown to bind to heparin (Guo, N., et al., J. B iol Ch. 257: 19349- 19355 (1992)). The affinity of this region to heparin has been proposed as part of the antigenic activity of TSP-1 (Guo, N., et al., J. Peptide Res. 49 (1997)). Among the five members of the TSP family of proteins, only TSP-1 and TSP-2 inhibit angiogenesis and contain the type I repeats (Tolsma et al., J. Cell, Biol. 122: 491-511 (1993)), Kyriakides, TR, et al. J. Cell. Biol. 140: 419-430 (1998)). Type I or properdin repeats were probably added to the TSP1 precursor and 2 by the intermixing of the exons approximately 500 and 900 years ago (Adams, J., et al., The T rhombospond Gene Family, 1 Ed. Molecular Biology Intelligence Unit (Springer, Ed.), RG Landes Company, Germany (1995)). It is feasible that the acquisition of this domain provided the precursor of TSP1 and TSP2 with the functions, such as the regulation of new blood vessels. More recently, BAI-1 (brain angiogenic inhibitor 1), a protein isolated from a brain protein for its ability to be regulated by p53, also showed that it contains the type I repeat of TSP-1 and provides the anti-inflammatory potential. -angiogenic to this molecule (Nishimori, H., et al., On co gen e 15: 2145-2150 (1997).) However, it seems that additional sequences or contexts are also important, since other proteins that contain the repeats of the Type I do not seem to have more or less clear established antiangiogenic properties such as: properdin, F-spondin, and other members of the complementary family.

Due to the presence of the TSP repeats in METH1 and METH2, together with their an- i-angiogenic properties, these proteins were originally considered members of the TSP superfamily. However, there is no additional homology to other TSPs, and in fact, similarity to TSP1. and TSP2 is restricted to type I repeats. In addition, proteins also have a strong sequence and homology to members of the ADAM family. These characteristics lead Kuno and colleagues to name ADAMTS to METHl mouse homologs (Kuno, K., et al., J.B.I., Ch., 272: 556-562 (1997)). The fresh identification of pNP1 and its sequence homology to the proteins described here leads to these three proteins being grouped in a subfamily called me t a 1 or sp or n i na s. At this point, it is not clear whether the pNIP has anti-angiogenic properties or whether METH1 and / or METH2 participate in the cleavage of the amino-terminal pro-peptide from procollagen to (I).

Example 2: Analysis by Northern and Southern transfer The total RNA was purified from the cells by extraction with guan i d i n i o - i s or t i o c i ana t as previously described (Chomczynski P. &Sacchi, N. Anal. Biochem 162: 156-159 (1987)). The poly (A) + RNA was extracted using a device from Boehringer Mannheim (BMB, I n d i a n a n d i i s, IN) according to the manufacturer's conditions. Other stained poly (A) + RNA were compared from Clontech (Palo Alto, CA). The p re-h ibri di zac ion was performed in a solution containing: 50% formamide, 6X SSPE, Denhardt IX solution, 0.1% SDS and 100 μg / ml hot denatured salmon sperm DNA for 12 hours. -18 hours at 42 ° C. Hybridization with labeled cDNA probes proceeded in the same elution at 42 ° C for 12-18 hours. The probes of TSP1 and METH1 corresponded to the complete human cDNAs. The METH2 probe corresponded to the Kp n i-E c or R I fragment of the human cDNA. A 1.3 Kb PstI fragment of g 1 ic xalde i do - 3 - f or s f a t o - of s h i dr o ge n a s (GPDH) was used to normalize the load and transfer efficiency. The membranes were exposed to the Kodak film Biomax MS (Kodak, New Haven, CT).

For spotting or Southern blots, human genomic DNA, compared to Promega (Madison, Wl), was heated at 65 ° C for 10 minutes and digested with E c oR I and Ps t l overnight at 37 ° C. 5 μg of digested DNA was separated on a 1% agarose gel, transferred to a nitrate membrane and cross-linked by ultraviolet light. The cDNA probes, thus, the conditions of p r e h i i i i i i a r and hybridization were identical to those described for spotting or Northern blots. The stains were washed with high severity (0.2X SSC, 0.2% SDS at 50 ° C).

The expression pattern of METH1 and METH2 was examined in both adult and embryonic tissues. Northern blot analysis was performed under highly stringent conditions with blots or blots that included poly (A) + RNA from human tissues. The METH1 and METH2 transcripts revealed a single band of 4.6 and 3.7 Kb, res ectively. Expression of abundant METH1 mRNA was observed in the adrenal glands, heart, placenta, followed by skeletal muscle, thyroid and stomach. From the embryonic tissues analyzed, the kidney showed the highest expression of METH1 mRNA. However, a weaker expression of METH1 mRNA was observed in all tissues analyzed. The distribution of METH2 mRNA was more restricted and weaker than that of METH1. The highest expression was observed in the lung, both in embryonic tissues and in adults. Interestingly, the expression of METH1 and METH2 does not seem to be overcome. In combination, the structural similarities and their transcription pattern suggest a functional network that is still different from transcriptional regulation. The expression levels of the TSP1 transcripts in the same spotted or blots were also analyzed, for comparison purposes. The highest expression of TSP1 mRNA was observed in the adult placenta and in all the embryonic tissues analyzed. In contrast to METH1 and METH2 constant levels of the TSP1 transcript were observed in all other tissues examined.

The distribution of cell types was also studied by staining or Northern blot analysis of poly (A) + RNA. METH1 mRNA was tect ab 1 e, at low levels, in the dermal fibrils, vascular smooth muscles, endometrial stromal cells, - and in two cancer cell lines, HeLa and G631, an adenocarcinoma and a melanoma, respectively. METH2 mRNA was detected only in SW480, a colon carcinoma cell line, but no expression was observed in any other of the cell lines or primary strains analyzed.

The possibility that the groups of angiogenic and anti-angiogenic factors regulate the formation of the vascular network in specific organs has been a hypothesis frequently discussed, and is considered as true although not yet proven. The expression patterns of METH1 and METH2, which are clearly different and almost not overlap, are randomized, at least with respect to the total levels. TSP1 and TSP2 also share identical structure, high level of amino acid similarity, although their expression patterns differ significantly (I ruel a-Ar i spe ML, D ev. Dyn. 1 9 7: 4 0 - 5 6 (1993) ). The differences are based on different cis-elements in their promoters and different mechanisms -regulators, as previously suggested. Although the promoters for METH1 and 2 have not been characterized, it is feasible that they provide unique characteristics for the regulation of each gene. However, the possibility that a motif, an ani - angiogenic repetition, with proven antigenic angiogenic properties present in several proteins with different tissue specificities is under consideration. Alternatively, small differences in sequence between the more closely related members of the same family might have significance in that it goes beyond functional redundancy. In the case of TSPl and TSP2, along with the structural similarities and perhaps having functionally common ant i -ang i ogenic properties, the TSP1 and TSP2 also seem to show functions in themselves and are not feasible to be shared with their families or similar related compounds. This becomes evident with the results of the two blocks for these genes. The animals-nudines with TSP1 exhibited mainly lung diseases (Lawler, J., et al., J. Clin.Invest.101: 982-992 (1998)) and secondarily vascular abnormalities, but only under specific pathological conditions or in a restricted set of organs. In contrast, mice blocked with TSP2 showed abnormalities in the set of collagen not predicted, 11 evading consequences to the skin, tendons, and bones (Kyriakides, TR, et al., J. Cell, Biol. 140: 419-430 (1998 )). In addition, these animals appear to have a total increase in capillary density in the dermis. It is not understood how the resemblance between the new described members of the me t a 1 family or sp ond i n a is functionally translated. Clearly, it has been shown that pNIP exhibits active proteolytic activity by cleaving the N-terminus of type I procollagen (Colidge, A., et al., Proc. Natl. Acad. Sci. USA 94: 2314-2319 (1997 )).

A second region of functional interest corresponds to the domain of disintegrin.

- This domain has been more fully characterized in the related members of the snake venom metalloproteases that have been shown to bind to allbß3 and inhibit the interaction of platelets by blocking coagulation (Pfaff, M., et al., Cell Adhes Commun 2: 491-501 (1994); Usami, Y., et al., Biochem. Biophys., Res. Commun. 201: 331-339 (1994)). The disintegrin portion consists of a thirteen to fifteen domain that frequently contains an RGD or a negatively charged residue at the aspartic acid position. The RGD, or equivalent, binds to integrins and serves as an antagonist or signaling ligands (Wolsberg, T.G. &; White, J.M., Developmental Biology 180: 389-401 (1996)). METH2, but not METH1, has a RGD sequence located in the amino-terminal domain of disintegrin. In addition, both molecules exhibit a relatively high, but not perfect, degree of conservation of the cysteines within the disintegrin motif. This seems to show an important role in the tertiary structure of this region and its ability to interact with integrins. In addition, some of these domains have been shown to act as functional adhesion molecules, particularly those with the transmembrane regions (Wolsberg, T.G. &White, J.M., Developmental Biology 180: 389-401 (1996)). It is not feasible that this is the case for METH1 and METH2, since both proteins appear to be secreted.

Example 3: Expression and purification of recombinant proteins The recombinant constructs for the expression of the truncated fusion proteins were as follows: pRSET-METH1- Type I: The METH1 nt 1605-1839 (from the start codon) was amplified by the polymerase chain reaction using the following primers : 5'-GCA TTT TGG ATC CGC CTT TTC ATG-3 '(SEQ ID NO: 78) and 5'-GTT GTG TGC TGC AGA TTG TTC C-3' (SEQ ID NO: 79). The amplified fragment was subcloned into the BamHl and PstI sites of the pRSET-vector; (2) pGEX-METH 1 -TSP was generated by ligating the ßamHI-EcoRI fragment from the pRS ET -METH 1 -TS P at the Smal site of the vector pGEX-5X (Pharmacia Biotech Inc., Piscataway, NJ) by ligation in the blunt end; (3) pGEX-1.0 -MET H 2: the nt 838-1818 fragment of the METH2 cDNA (from the start codon) was ligated into the BaipHI-EcoRI sites of pGEM-2TK. The METH2 fragment was amplified by PCR using the following primers: 5'-GAAAATGGGGATCCGAGGTG-3 '(SEQ ID NO: 80) and 5'-GCAGGAGAATTCCGTCCATG-3' (SEQ ID NO: 81) to generate the restriction sites Ba mñ ly l coRI; (4) pGEX-METH2-TSP: a 0.5 Kb fragment from Xm to l-E c or R l was isolated from pGEX-1.0-METH2 and subcloned at sites Xm a l and E c or R I of vector pGEX-2TK. All the constructs were sequenced to verify the fidelity of the sequence and correct the open reading structure.

The recombinant proteins were named 6H-METH1, the recombinant protein expressed with the plasmid pRS ET -MET H1-TSP, GST-METH1, - the protein expressed with the plasmid pGEX-METH1-TSP and GST-METH2, the expressed protein with the pGEX-MET H 2 -TSP plasmid.

The expression plasmids were transformed into the E strain. c o l i BL 21: D E 3 (Stratagene Cloning Systems, La Jolla, CA) and the fusion proteins were induced following the manufacturer's recommendations. Briefly, pellets of induced bacteria were resuspended in PBS and treated with sound on ice for 1 minute. The suspension was subsequently incubated at room temperature for 20 minutes in the presence of 1% triton X-100 and centrifuged at 4 ° C. The histidine-labeled fusion proteins were then purified in Ni-NTA beads (Qiagen, Chatsworth , CA) incubating 20 ml of the supernatant with 1 ml of beads (50% suspension) for 2 hours at 4 ° C. The suspension was transferred to a column and washed with 10 volumes of PBS columns containing 10 mM imidazole, followed by 50 mM imidazole and finally 100 mM imidazole.

- The protein was eluted with 500 mM imidazole in PBS. The fractions containing the recombinant protein were dialyzed against DMEM free of phenol red. The samples were centrifuged for 30 minutes at 4 ° C, part of the protein was not soluble and was lost during centrifugation. The supernatant was stored at -70 ° C and used for proliferation of the cornea bag and the chorioallantoic membrane (CAM) assays.

For the purification of the GST fusion proteins, the extract was cleaned by centrifugation and applied to an affinity column with GST (Pharmacia). The column was washed with PBS-triton X-100 1% in the presence of reduced glutathione 0.1 mM and, subsequently, with the same buffer in the presence of reduced glutathione 0.5 mM. The fusion proteins were eluted with 10 mM reduced glutathione in 50 mM Tris-HCl, pH 7.5. the fractions containing the protein were dialyzed against DMEM, stored at -70 ° C and used for proliferation assays, corneal pouch and chorioallantoic membrane (CAM).

The integrity and purity of the recombinant proteins were analyzed in 12.5% or 15% acrylamide gels stained with Cooma s blue.

A recombinant GST fusion protein containing the first two type I repeats of TSP was also dialyzed against DMEM before being used in the functional assays. The intact TSP1 was purified from the platelets as previously described Roberts, D.D., et al., J. Tissue Cult. Methods 16: 211-222 (1994)).

To test the hypothesis that the TSP domains of METH1 and METH2 could function as regulators of angiogenesis, recombinant fusion proteins were generated in the bacteria. The constructs included the first TSP domains of METH1 or METH2. This domain is the most conserved, 52% similarity of -amino acids with the second type I repeat of TSP1, (this domain contains a putative binding site for CD36). All recombinant proteins were isolated under native conditions to preserve their secondary structure as much as possible. The 6H-METH1 and GST-METH1 contained the first TSP-like domain of METH1 fused to a histidine tag or a GST, respectively. The recombinant METH1 protein was made with two different brands due to the purification and structural advantages. The differences in size are due to the size of the mark, 6 kDa of histidine and 27 kDa of GST. The GST-METH2 contained the first TSP domain of METH2 also fused to a GST. A fragment corresponding to the last two type I repeats of TSP1 was also fused to a GST, and the intact TSP1 was purified from the platelets that were used as positive controls. In addition, GST was only included in all experiments as a negative control.

- - Example 4: TSP domains in the rupture of angiogenesis in vivo due to METH1 and METH2 Cornea Pocket Test Swiss Webster males and females were purchased from Charles River (Boston, MA) and used between 8-10 weeks of age for implant pellets. The cornea bags were made as described by Kenyon and colleagues (Kenyon, B.M., et al., Invest. Ophtalmol. Vis. Sci. 37: 1625-1632 (1996)) with few modifications. Briefly, a solution of 10 μg of recombinant bFGF plus 5 mg sucralfate was mixed with 10 μl of Hydron (200 mg / ml in ethanol, New Brunswick, NJ) and the recombinant protein of interest (2 μg). The suspension was then sprayed on a sterile nylon mesh frame (pore size 500 μm, Tetko Inc., Briarcliff Manor, NY) and allowed to dry for 30 minutes. The fibers of the mesh were pulled to produce 500 μm pellets which were stored at -20 ° C. Pellets of uniform size were selected under a microscope and used for testing.

The mice were anesthetized with Avertin. An incision was made in the cornea using a Nikon SMZ-U dissecting microscope with the help of a scalpel. A single pellet was implanted in the bag or pocket. Five days after implanting the pellet, angiogenesis of the cornea was evaluated and photographed.

In yes to me CAM Chorioallantoic membrane assays were performed on Leghorn chicken embryos (SPAFAS, MA) at 12-14 days of embryonic development. Matrigel (750 μg / ml), VEGF (250 ng / mesh) and the protein or peptide that was tested were mixed, placed on nylon meshes (pore size 500 μm, Tetko Inc.) and incubated sequentially at 37 ° C for 30 minutes and at 4 ° C during 2 hours to induce polymerization.

- -A positive control was also prepared (matrigel and VEGF) and one negative (VEGF only) for each CAM. The polymerized meshes were placed in a third region of the CAM and incubated for 24 hours. To visualize the containers, 400 μl of fluorescein isothiocyanate dextran was injected (10 mg / ml, SIGMA) in the bloodstream of the chickens. After 5-10 minutes of incubation, the chicken was fixed topically with 3.7% formaldehyde for 5 minutes. The meshes were then dissected and mounted on jet carriers. The intensity of the fluorescence was analyzed with a computer-aided imaging program (NIH Image 1.59).

The peptides used in these assays were synthesized by Chiron (Raleigh, NC). The sequence corresponded to the amino acids: P-TSP1, 430-447; P-METH1, 549-563; P-METH2, 529-548.

The evaluation of angiogenic or genetic responses is important in the sensitivity and specificity of the tests used to assess the response. To evaluate the an- i -angiogenic activity of these fragments i n vi, two were used. popular and well-accepted angiogenesis assays: the cornea pocket and the chorioallantoic membrane. Visibility, accessibility, and corneal avalanche are highly advantageous and facilitate the visualization of neovascular response and topical application of test substances. A known amount of the factor or factors of angiogenesis was implanted, like a pellet, into a bag made in the eye of the cornea. To test an inhibitor of angiogenesis, the molecule was implanted with the stimulator in the same pellet, and the response was compared to the stimulator alone.

In these experiments, bFGF was used as the vascularization stimulator. The pellets containing the recombinant protein were implanted in the mouse corneas and their ability to inhibit the angiogenic response induced by bFGF was compared to that of the controls. When a pellet of bFGF containing GST was implanted, new capillaries grew from the limbus of the cornea, towards the pellet in 5 days. In contrast, the addition of GST-METH1 or GST-METH2 to the bFGF pellets completely nullified the growth of the blood vessels. Table 4 contains a summary of the results obtained from the 41 tests carried out. The intact purified TSP1 of the platelets and GST-TSP1 were used as positive controls. The assays were performed at identical concentrations, suggesting that METH1 and METH2 have a similar potency to that of TSP1 in the inhibition of angiogenesis. In addition, when half of the standard concentration was used, a remarkable, weak response was observed indicating a dose-dependent effect.

- - In the CAM assay, the angiogenic response was analyzed by measuring the number of blood vessels that grew within a matrix polymer containing the angiogenic growth factor. To determine whether the recombinant proteins METH1 and METH2 inhibited neovascularization in the CAM assay induced by VEGF, a matrigel polymer containing VEGF and the recombinant protein were implanted in the CAM. The quantitative analysis of the experiments, which included three different polymers per treatment are shown in Figure 6A. Polymers of matrigels containing VEGF - plus 5 μg of GST-METHl or GST-METH2 caused a greater inhibition of 80% in the growth of blood vessels. A similar potency was found using the recombinant protein GST derived from the type I repeats of the TSP1. In addition, the anti-angiogenic effect of the TSP domains in METH1 and METH2 was dose dependent with complete inhibition of blood vessel growth when 15 μg / ml of the protein was used (Figure 6C and D). The GST alone, at identical concentrations, did not have a significant effect on angiogenesis stimulated by VEGF.

The synthetic peptides of the second or third type I repeats of human TSP1 can mimic the anti-angiogenic effects of intact TSP1 (Tolsma, S.S., et al., J. Cell X Biol. 122: 491-511 (1993)). In fact, a 19-residue polypeptide showed that it is sufficient to block neovascularization in vivo in the cornea of rats and to inhibit the bFGF-induced migration of cultured endothelial cells (Vogel, T., et al., J Cell. Biochem 53: 14-84 (1993)); fTolsma, S.S., et al. , J. Cell. Biol. 122: 497-511 (1993)). To test whether it was true for the TSP domains of METH1 and METH2, the peptides derived from the same region were synthesized and their activity at n t i - an i i g e n i c o was evaluated in the CAM assay. The results were shown in Figure 6B. Peptides derived from both the TSP domain of angiogenesis induced by VEGF blocked with METH1 and METH2 similar to that of TSP1. In contrast, the mixed peptides had no significant effect.

Example 5: Proliferation assays Human dermal endothelial cells (HDEC) were isolated and grown in Petri dishes coated with Vitrogen ™ in EBM (Clonetics, San Diego, CA) supplemented with 15% fetal calf serum, 25 μg / ml cAMP, and 1 μg / ml of hydrocort isone-21-acetazole were used from steps 3 to 6. Cells were quiescent by incubating the confluent monolayers with phenol red-free EBM containing 0.2% BSA for 48 hours. Human dermal fibroblasts were isolated from the skin of the neonatal forehead and by enzymatic dissociation. Both smooth muscle cells and fibroblasts were maintained in DMEM supplemented with 10% fetal calf serum. Human mammary epithelial cells (HMEC) from Clonetics were purchased and maintained in the recommended medium (mammary epithelial growth medium, MEGM).

Human, quiescent dermal endothelial cells, between steps 3 and 6, were placed in 26 well plates coated with Vitrogen ™ in EBM supplemented with 0.2% BSA, 0.1% fetal calf serum and 1 ng / ml bFGF in the presence or absence of the recombinant protein and incubated in 5% CO2 at 37 ° C for 48 hours. For fibroblast and vascular smooth muscle (VSM) proliferation assays, the cells were incubated under the same conditions using DMEM instead of EBM. Human mammary epithelial cells were incubated in their growth medium. A pulse of ['H] -T imi di na (1 μCi / μl) was added during the last 4 hours before harvesting. The cells were washed and fixed in 10% TCA. The incorporation of [3 H] -Timidine was determined by scintillation counting, as previously described (I rue la-Ar i spe M.L., &Sage, E.H., J. Ce l l. B i o ch em 52: 4 1 4 (1993)).

The statistical analysis was done using an In-Stat computer program (Graph Pad Software) for the Macintosh. Assuming normal distributions, the data were analyzed using a one-way ANOVA, followed either by the Dunnett T test for comparisons between the groups, or the student-Newman-Kleus test for multiple comparisons between the groups.

To obtain an internal view of the mechanism by which METH1 and METH2 - inhibit neovascularization, the direct effect of purified recombinant fusion proteins on proliferation of endothelial cells was tested. The endothelial cells harvested in the serum were placed in a growth medium containing bFGF and FCS. Recombinant proteins (3 μg / ml were added at the same time as the plates were placed.) 40% inhibition (GST-METHl), 45% (6H-GST) or 36% (GST-METH2) was observed, in contrast to a non-significant effect when GST was added alone The recombinant protein of TSPI type I repeats had similar inhibitory effects (Figure 7A) In addition, the suppression of proliferation mediated by METH1 or METH2 were dose dependent, as shown Figure 7E: Inhibition was observed as early as one day after treatment and the inhibitory effect was non-toxic and reversible since the removal of the recombinant protein and the subsequent addition of the growth factor alone, led to the onset of proliferation of endothelial cells.

- - The cellular specificity of the effects at n t i -p r o 1 i fe r a t i vo for METH1 and METH2 on the endothelium was evaluated by additional proliferation assays in a variety of non-endothelial cells. No significant inhibition of proliferation was observed in cultures of smooth muscle cells or fibroblasts. In contrast, a non-significant but reproducible stimulation of the proliferation for these two cell types could be observed. These results regulate the presence of any potential non-specific inhibitor of cell growth in the preparations of the recombinant protein. In mammary epithelial cells, however, METH1 and METH2 inhibited cell proliferation to the same extent as endothelial cells. Interestingly, TSP1 also suppresses mammary epithelial cell proliferation both in vivo and in the transgenic model.

The possibility that METHl and - -METH2 could act as d i s i n t e g r i n s is consistent with their antiangiogenic properties. The clear blockade of avß3 and ßl integrins with antibodies has been shown to inhibit neovascularization both during development and in tumors (Brooks, PC, et al., Cell 55: 683-693 (1996); Brooks, PC et al. ., Cell 52: 391-400 (1998); Senger, DR, et al., Proc. Natl. Acad. Sci. USA 94: 13612-13617 (1997)). Integrins are essential for the mediation of both proliferative and migratory ones (Schwartz, MA &Ingber, DE, Mol. Biol. Cell 5: 389-393 (1994)), therefore the interference with those signals can be highly harmful. for the angiogenic process. Functional angiogenic assays were performed with the recombinant protein containing only the type I repeats in METH1 and METH2.

The mechanism of action of METHl and METH2 in relation to its angio-inhibitory activity is not shown. Until now, there is evidence that these proteins are secreted and linked to endothelial cells. Additional research is directed towards the identification of the transduction mechanisms of signals and receptors. A similar hypothesis results from the lessons learned from TSP1 in which both METHl and METH2 are linked to CE36. Recently, this purifying receptor has been involved in the mediation of signals by which the TSP-1 exerts its anti-angiogenic effects (Dawson, D.W., et al., J. Cell. Biol. 138: 101-111 (1991)). Both the sequences CSVTCG (SEQ ID NO: 83) (Asch, AS, et al., Nature 262: 1436-1 39 (1993); Catimel, B., et al., Biochem. J. 284: 231-236 (1992) ) as the GCQXR (SEQ ID NO: 84) have been proposed as main binding motifs for CD36 (Dawson, D. W., et al., J. Cell, Biol. 138: 707-717 (1997)). METHl and METH2 have almost complete conservation in both regions. A complementary and similar appearance is the binding of METH1 and METH2 to bFGF. The binding to heparin and bFGF has been proposed as part of the anti-angiogenic activity of TSP1 (Guo, N., et al., J. Peptide Res. 49 (1997)). This property seems to be mediated through the WSXWS motif (SEC.ID NO: 82), also preserved in METHl and METH2. Future efforts will be focused on the signals involved in the antigenic properties mediated by these new proteins and their potential as extracellular proteases.

Example 6: Ai s 1 ami in t or of the cDNA Clone of METHl or METH2 from the Sample Dep os i tada Two methodologies can be used to isolate METH1 or METH2 from the deposited sample. First, the deposited clone is transformed into a suitable host or host (such as Blue XL-1 (Stratagene)) using techniques known to those skilled in the art, such as those provided by the vector supplier or in patents or publications. related Transformants are plated on 1.5% agar plates (containing the appropriate selection agent, eg, ampicillin) to a density of about 150 transformants (colonies) per plate. A single colony is then used to generate the DNA using nucleic acid isolation techniques well known to those skilled in the art (eg, Sambrook et al., Molecular Cloning: A Laboratory 7 Manual, 2nd Edit., (1989), Cold Spring Harbor Laboratory Press).

Alternatively, two primers of 17-20 nucleotides derived from both ends of SEQ. ID NO: 1 or SEC. ID NO: 3 (ie, within the region of SEQ ID NO: 1 or SEQ ID NO: 3 linked by 5 'NT and 3' NT of the clone) were synthesized and used to amplify the cDNA of METHl or METH2 using the cDNA plasmids as templates or patterns. The reaction of the polymerase chain is carried out under routine conditions, for example, in 24 μl of the reaction mixture with 0.5 μg of the above cDNA standard. A convenient mix of reaction is MgCl2 1.5-5 mM, 0.01% gelatin ('w / v), 20 uM each of dATP, dCTP, dGTP, dTTP, 25 pmol of each primer and 0.25 Polymerase Units Taq Thirty-five cycles of PCR (denaturation at 94 degrees C for 1 minute, cooling and heating at 55 degrees C for 1 minute, elongation at 72 degrees C for 1 minute) were performed with a thermal cycle generator, automated Perkin-Elmer Cetus . * The amplified product was analyzed by agarose gel electrophoresis and the DNA band with the expected molecular weight was cut and purified. The PCR product was verified to be in the selected sequence by subcloning and sequencing the DNA product.

Several methods are available for the identification of the 5 'or 3' non-coding portions of the METH1 or METH2 gene that may not be present in the deposited clones. These methods include but are not limited to, primed with the -filter, enrichment of the clone using specific probes, and protocols similar or identical to the 5 'and 3' "RACE" protocols that are well known in the art. For example, a method similar to 5 'RACE is available to generate the missing 5' end of a desired full length transcript (Fromon t -Ra ci ne et al., Nu cl eic A ci ds R is 21 (7) : 1683-1684 (1993)).

Briefly, a specific RNA oligonucleotide is ligated to the 5 'ends of a population of RNA that presumably contains the full-length gene RNA transcripts. A first set containing a specific primer to the ligated oligonucleotide and a specific primer to a known sequence of the METH1 or METH2 gene of interest is used to PCR amplify the 5 'portion of the full length gene of METH1 or METH2. This amplified product is subsequently sequenced and used to generate the gene of length comp 1 e t a. - 44 - This previous method starts with the total isolation of the RNA from the desired source, although poly-A + RNA can be used. The RNA preparation can be treated with phosphatase if necessary to remove the 5 'phosphate groups or degraded or damaged RNA that can interfere with the last stage of the RNA ligase. The phosphatase should then be inactive and the RNA treated with p i r or f or s f a t a s of tobacco acid to eliminate the final structure present at the 5 'ends of the messenger RNAs. This reaction leads to the 5 'phosphate group at the 5' end of the RNA cleaved from its terminus which can then be ligated to an RNA oligonucleotide using the T4 RNA ligase.

This preparation of modified RNA is used as a template for the synthesis of the first strand of cDNA using an oligonucleotide specific to the gene. The synthesis reaction of the first strand is used as a standard for PCR amplification of the desired 5 'end using a specific primer to the ligated RNA oligonucleotide and a specific primer to the known sequence of the gene of interest. The resulting product is then sequenced and analyzed to confirm that the 5'-end sequence belongs to the METH1 or METH2 gene.

Ex empl o 7: Expression Ba c teri ana of ME THl or METH2 A METH1 or METH2 polynucleotide encoding a METH1 or METH2 polynucleotide of the invention is amplified using the PCR oligonucleotide primers corresponding to the 5 'and 3' ends of the DNA sequence, as outlined in Example 5 to synthesize the insertion fragments. The primers used to amplify the cDNA insert should preferably contain restriction sites such as BamHI and Xbal, at the 5 'end of the primers to clone the amplified product in the expression vector. For example, BamHl and Xbal correspond to the sites of the restriction enzyme in the pQE-9 bacterial expression vector (Qiagen, Inc., Chatsworth, CA). This plasmid vector encodes antibiotic resistance (Ampr), a bacterial origin of replication (ori), an IPTG (P / O) regulator / operator, a ribosome binding site (RBS), a 6-mark histidine (6-His), and cloning sites of the restriction enzyme. The pQE-9 vector is digested with BamHI and Xbal and the amplified fragment is ligated into the pQE-9 vector maintaining the reading structure initiated in the bacterial RBS. The ligation mixture is then used to transform the E. coli strain M15 / rep4 (Qiagen, Inc.) which contains multiple copies of plasmid pREP4, which expresses the lacl repressor and also confers resistance to kanamycin (Kanr) Transformants were identified by their ability to grow on LB plates and colonies resistant to the amyloid i / i / i am / kan ami c i na are selected. The plasmid DNA is isolated and confirmed by restriction analysis.

The clones containing the desired constructs are grown overnight (0 / N) in a liquid culture in an LB medium supplemented with both Amp (100 ug / ml) and Kan (25 ug / ml). The O / N culture is used to inoculate a large crop at a ratio of 1: 100 to 1: 250. The cells were grown to an optical density of 600 (O.D.600) of between 0.4 and 0.6. The IPTG (Piranoside de i s op rop i 1-B-D- t i oga 1 a c t o) is then added until a final concentration of 1 mM. IPTG induces the lacl repressor by activation, eliminating the P / O and leading to increased expression of the gene.

The cells are grown for 3 to 4 extra hours. The cells are then harvested by centrifugation (20 min at 6000 Xg). The cell pellets are solubilized in the chaotropic agent 6 Molar Guanidine HCl by shaking for 3-4 hours at 4 degrees C. The cell debris is removed by centrifugation and the supernatant containing the polypeptide is loaded onto an affinity resin column - nickel-nitrile-tri-acetic acid ("Ni-NTA") (available from QIAGEN, Inc., supra). 6 x His tagged proteins bind to Ni-NTA resin with high affinity and can be purified in a simple one-step procedure (for details see: QIAexpressioni s t (1995) QIAGEN, Inc., s upra).

Briefly, the supernatant is loaded onto the column in guanidine 6 M-HCl, pH 8, the column is first washed with guanidine 6 M-HCl, pH 8, then washed with 10 volumes of 6 M guanidine-HCl, pH 6, and finally the polypeptide is eluted with 6 M guanidine-HCl, pH 5.

The purified METH1 or METH2 protein is renatured by dialysis against phosphate buffered saline (PBS) or 50 mM Na-acetate, pH 6 buffer plus 200 mM NaCl. Alternatively, the METH1 or METH2 protein can be redoubled successfully while immobilizing on the Ni-NTA column. The recommended conditions are as follows: Ren a t um u al using a gradient of 6M-1M linear urea in 500 mM NaCl, 20% glycerol, 20 mM Tris / HCl, pH 7.4, containing the protease inhibitors. The renaturation must be done during a period of 1.5 hours or more. After the treatment, the proteins are eluted by the addition of 250 mM imidazole. The imidazole is removed by a final dialysis step against PBS or 50 mM sodium acetate buffer pH 6 plus 200 mM NaCl. The purified METH1 or METH2 protein is stored at 4 ° C or frozen at -80 ° C.

In addition to the above expression vector, the present invention further includes an expression vector comprising the phage operator and promoter elements operably linked to a METH1 or METH2 polynucleotide, called pHE4a. (Accession Number ATCC 209645, filed on February 25, 1998). This vector contains: 1) a gene of n eomi ci n f o s f o t ran s f a r a s as a selection marker, 2) an origin of E. -c ol i of replication, 3) a phage promoter sequence T5, 4) two operator sequences l a c, 5) a Shine-Delgarno sequence, 6) the repressor gene of the lactose operon (laclq). The origin of replication (oriC) is derived from pUC19 (LTI, Gaithersburg, MD). The promoter sequence and operator sequences are manufactured synthetically.

DNA can be inserted into the pHEa by restricting the vector with Ndel and Xbal, BamHl, Xhol, or Asp718, running the restricted product on a gel, and isolating the largest fragment (the largest fragment should be approximately 310 pairs of base). The DNA insert is generated according to the PCR protocol described in Example 5, using PCR primers that have restriction sites for Ndel (5 'primer) and Xbal, BamHl, Xhol, or Asp718 (primer 3 '). The PCR insert is gel purified and restricted with compatible enzymes. The insert and the vector are ligated according to standard protocols.

- - The genetically engineered vector could easily be substituted in 'the above protocol to express the protein in a bacterial system.

Example 8- 'Purification of the METH1 or METH2 Polypeptide from an Infiltration Body The following alternative method can be used to purify the METH1 or METH2 polypeptide expressed in E. coli when it occurs in the form of inclusion bodies. Unless otherwise specified, all of the following steps are conducted at 4-10 ° C.

After completion of the production phase of E. coli fermentation, the cell culture is cooled to 4-10 degrees C and the cells are harvested by continuous centrifugation at 15,000 rpm (Heraeus Sepatech). Based on the expected yield of the protein per unit weight of cell paste and the amount of protein -purified required, an appropriate amount of cell paste, by weight, is suspended in a buffer solution containing 100 M Tris, 50 mM EDTA , pH 7.4. The cells are dispersed to a homogeneous suspension using a high cut mixer.

The cells are then lysed by passing the solution through a microtiter cell (Mi crof luidics, Corp. or APV Gualin, Inc.) twice at 4000-6000 psi. The homogenate is then mixed with a NaCl solution to a final concentration of 0.5 M NaCl, followed by centrifugation at 7000 xg for 15 minutes. The resulting pellets are washed again using 0.5 M NaCl, 100 mM Tris, 50 mM EDTA, pH 7.4.

The resulting washed wash bodies are solubilized with 1.5 M guanidine hydrochloride (GuHCl) for 2-4 hours. After centrifugation at 7000 xg for 15 minutes, the pellets are discharged and the polypeptide containing the supernatant is incubated at 4 degrees C overnight to allow additional extraction of GuHCl.

Following centrifugation at high speed (30,000 xg) to eliminate the insoluble particles, the protein solubilized in GuHCl is doubled by rapidly mixing the GuHCl extract with 20 volumes of the buffer containing 50 mM sodium, pH 4.5, 150 mM NaCl, 2 mM EDTA by vigorous agitation. The solution of the diluted protein, redoubled, is kept at 4 degrees C without mixing for hours before the subsequent stages of purification.

To clarify the redoubled polypeptide solution, a pre-prepared tangential filtration unit equipped with a membrane filter of 0.16 μm with an appropriate surface area (eg, Filtron), equilibrated with 40 mM sodium acetate, pH 6.0 is employed. the filtered sample is loaded on a cation exchange resin (for example, Poros HS-50, Perseptive Biosystems). The column is washed with 40 mM sodium acetate, pH 6.0 and eluted with 250 mM, 500 mM, 1000 mM and 1500 mM NaCl in the same buffer, in a step-by-step manner. The abs o_rb a n c a 280 nm of the effluent is monitored continuously. The fractions are collected and analyzed further by SDS-PAGE.

The fractions containing the METH1 or METH2 polypeptide are then combined and mixed with 4 volumes of water. The diluted sample is loaded onto a set of previously prepared tandem columns of strong anion exchange resins (Poros HS-50, Perseptive Biosystems) in weak anion (Poros CM-20, Perseptive Biosystems). The columns are equilibrated with 40 mM sodium acetate, pH 6.0. Both columns are washed with 40 mM sodium acetate, pH 6.0, 200 M NaCl. The CM-20 column is then eluted using a 10-column linear volume gradient ranging from 0.2 M NaCl, 50 mM sodium acetate, pH 6.0 to 1.0 M NaCl, -50 mM sodium acetate, pH 6.5. The fractions are collected under constant monitoring A280 of the effluent. The fractions containing the polypeptide are subsequently combined (determined, for example, by 16% SDS-PAGE) The resulting METH1 or METH2 polypeptide should exhibit a purity greater than 95% after the aforementioned redo and purification steps. No larger contaminant bands should be observed from coomassie blue staining on 16% SDS-PAGE gel when 5 ug of purified protein is loaded. The purified METH1 or METH2 protein can also be tested for endotoxin contamination / PS, and typically the LPS content should be less than 0.1 ng / ml according to the LAL assays.

- -Example 9: Cloning and Expression of METH1 or METH2 in an Expression System of Ba cul ovirus In this example, the plasmid pA2 plasmid transporter is used to insert the METH1 or METH2 polynucleotide into a baculovirus to express METH1 or METH2. This expression vector contains the strong polyhedrin promoter of Autographa californica nuclear polyhedrosis virus (AcMNPV) followed by convenient restriction sites such as BamHI, Xba I and Asp718. The polyadenylation site of simian virus 40 ("SV40") is used for efficient polyadenylation. For easy selection of recom- binant virus, the plasmid contains the beta-galactosidase gene of E. coli under control of a weak Drosophila promoter in the same orientation, followed by the polyadenylation signal of the polyhedrin gene. The inserted genes are flanked on both sides by viral sequences by homologous recombination - mediated by cells with viral DNA of the native type to generate a viable virus expressing the cloned METH1 or METH2 polynucleotide.

Many other baculovirus vectors can be used in place of the above vector, such as pAc373, pVL941, and pAcIMl, as one skilled in the art could readily appreciate, as long as the construct provides appropriately localized signals for transcription, translation, secretion and similar, which include a signal peptide and an AUG in the frame as required. Such vectors are described, for example, in Luckow et al., Virology 170: 31-39 (1989).

Specifically, the cDNA sequence of METH1 or METH2 contained in the deposited clone, which includes the AUG initiation co-ordination, and any naturally associated leader sequences, is amplified using the PCR protocol I wrote in Example 5. If the sequence of signal occurring - - naturally used to produce the secreted protein, the pA2 vector does not need a second signal peptide. Alternatively, the vector can be modified (pA2 GP) to include a baculovirus leader sequence, using the standard methods described in Sum et al., "A Manual of Methods for Baculovirus Vectors and Insect Cell Culture Procedures," Texas Agricultural Experimental Station Bulletin No. 1555 (1987).

The amplified fragment is isolated from a 1% agarose gel using commercially available equipment ("Geneclean," BIO 101 Inc., La Jolla, Ca.). The fragment is then digested with the appropriate restriction enzymes and again purified on a 1% agarose gel.

The plasmid is digested with the corresponding restriction enzymes and optionally, it can be used using calf intestinal phosphatase, using routine procedures known in the art. The DNA is then isolated from a 1% agarose gel using commercially available equipment ("Geneclean," BIO 101 Inc., La Jolla, Ca.).

The fragment and the dephosphorylated plasmid are ligated together with a T4 DNA ligase. The HB101 of E. c or l i or other suitable guests of E. As the XL-1 Blue cells (Stratagene Cloning Systems, La Jolla, CA) are transformed with the ligation mixture and placed in culture dishes. The bacteria containing the plasmid are identified by digestion of DNA from individual colonies and the digestion product is analyzed by gel electrophoresis. The sequence of the cloned fragments is confirmed by DNA sequencing.

Five ug of a plasmid containing the polynucleotide was co-transfected with 1.0 ug of commercially available linearized baculovirus DNA ("BacaloGold3 baculovirus DNA", Pharmingen, San Diego, CA), using the lipofection method described by - -Felgner et al., Proc. Natl. Acad. Sci. USA 84: 7413-7417 (1987). One ug of the BaculoGold3 virus DNA and 5 ug of the plasmid are mixed in a sterile well of a microtiter plate containing 50 ul of serum free Grace's medium (Life Technologies Inc., Gaithersburg, MD). Subsequently, 10 ul of Lipofectin plus 90 ul of Grace's medium are added, mixed and incubated for 15 minutes at room temperature. The transfection mixture is then added dropwise to the Sf9 insect cells (ATCC CRL 1711) seeded on a 35 mm tissue culture plate with 1 ml of Grace's medium without serum. The plate is then incubated for 5 hours at 27 degrees C. The transfection solution is then removed from the plate and 1 ml of Grace's insect medium supplemented with 10% fetal calf serum is added. The culture was then continued at 27 degrees C for four-days.

After four days the supernatant is harvested and an assay is performed on the plate, as described by Summers and Smith, supra. An agarose gel with "Blue Gal" (Life Technologies Inc., Gaithersburg) is used to allow easy identification and isolation of gal-expressing clones, which produce plates stained blue.

(A detailed description of a "plaque assay" of this type can also be found in the user guide for insect cell cultures and bactericide distributed by Life Technologies Inc., Gaithersburg, page 9-10). After the appropriate incubation, the blue stained plates are collected with the tip of a micropipette (e.g., Eppendorf). The agar containing the recombinant viruses are then resuspended in a microfuge tube containing 200 ul of Grace's medium and the suspension containing the recombinant baculovirus is used to infect the Sf 9 cells seeded on 35 mm plates. Four days later the supernatants of these culture plates are harvested and then stored at 4 degrees C.

To see the expression of the - -polypeptide, the Sf 9 cells are grown in Grace's medium supplemented with 10% FBS inactivated by heat. The cells are infected with the recombinant baculovirus containing the polynucleotide at a multiplicity of infection ("MOI") of about 2. If radioiodine proteins are desired, the medium is removed 6 hours later and replaced with the SF900 II medium minus methionine and cysteine (available from Life Technologies Inc., Rockville, MD). After 42 hours, 5 uCi of 35S-methionine and 5 uCi of 35S-cysteine (available from Amersham) are added. The cells are subsequently incubated for 16 hours and then harvested by centrifugation. The proteins in the supernatant as well as the intracellular proteins are analyzed by SDS-PAGE followed by au t o -r ad i or g r a f a (if they are adhered to).

The amino acid sequence of the amino-terminal amino acid sequence or the purified protein can be used to determine the amino-terminal sequence of the METH1 or METH2 protein produced.

Ex empl o 1 0: Expres s ion of ME THl or ME TH 2 in l a s c he u l s s of mamí f e s The METH1 or METH2 polypeptides can be expressed in a mammalian cell. A mammalian expression vector, typically, contains a promoter element, which mediates the initiation of mRNA transcription, a sequence encoding the protein, and signals required for the termination of transcription and polyadenylation of the transcript. Additional elements include enhancers, Kozak sequences and intervening sequences flanked by donor and acceptor sites for RNA splicing. Highly efficient transcription is performed with SV40 early and late promoters, the long terminal repeats (LTR) of Retroviruses, eg, RSV, HTLVI, HIVI and the cytomegalovirus early promoter (CMV). However, cellular elements can also be used (for example, the human actin promoter).

- - Expression vectors suitable for use in the practice of the present invention include, for example, vectors such as pSVL and pMSG (Pharmacia, Uppsala, Sweden), pRSVcat (ATCC 37152), pSV2DHFR (ATCC 37146), pBC12MI (ATCC 67109 ), pCMVSport 2.0, and pCMVSport 3.0. Mammalian host cells that could be used include, human Hela, 293, H9 and Jurkat cells, mouse NIH3T3 and C127 cells, Cos 1, Cos 7 and CV1 cells, as well as QC1-3 quail cells, mouse L cells and Chinese hamster ovary cells (CHO).

Alternatively, the METH1 or METH2 polypeptide can be expressed in stable cell lines containing the polynucleotide METH1 or METH2 integrated into a chromosome. Co-transfection with a selectable marker such as DHFR, gpt, neomycin, hygromycin, allows the identification and isolation of the transfected cells.

The transfected METH1 or METH2 gene can also be amplified to express large amounts of the encoded protein. The DHFR marker (dihydrofolate reductase) is useful in the development of cell lines that carry several or even several hundred copies of the gene of interest. (See, eg, Alt, FW, et al, J Biol Chem 253: 1357-1370 (1978); Hamlin, JL and Ma, C., Biochem et B Ophys Acta 1097:... 101-.?. 143 (1990); Page, MJ and Sydenham, MA, Biotechnology 9: 64-68 (1991)). Another useful selection marker is the enzyme glutamine synthase (GS) (Murphy et al., Biochem J. 227: 277-279 (1991); Bebbington et al., Bio / Technology 10: 169-115 (1992).

Using these markers, the mammalian cells are grown in selective media and the cells with the highest resistance are selected. These cell lines contain a gene or amplified genes integrated into a chromosome. The Chinese hamster ovary (CHO) and NSO cells are often used for the production of proteins.

The derivatives of the plasmid pSV2-DHFR - - (Accession No. ATCC 37146), the pC4 expression vectors (Accession No. ATCC '209646) and pC6 (Accession No. ATCC 209647) contain the strong promoter (LTR) of the Rous Sarcoma Virus (Cullen et al., Molecular and Cellular Biology, 438- 447 (March, 1985)) plus a fragment of the CMV enhancer (Boshart et al., Cell 41: 521-530 (1985)). Multiple cloning sites, for example, with the sites of. Cleavage of the restriction enzyme BamHl, Xbal and Asp718, facilitate the cloning of METH1 or METH2. The vectors also contain the 3 'intron, the polyadenylation and termination signal of the prep r or i nsul i na gene of the rat, and the mouse DHFR gene under the control of the SV40 early promoter.

If a naturally occurring signal sequence is used to produce a secreted protein, the vector does not need a second signal peptide. Alternatively, if a naturally occurring signal sequence is not used, the vector can be modified to include a heterologous signal sequence in an effort to secrete the cell protein. (See, for example, WO 96/34891).

The amplified fragment is then digested with the appropriate restriction enzyme and purified on a 1% agarose gel using commercially available equipment ("Geneclean," BIO 101 Inc., La Jolla, Ca.). The isolated fragment and the vector of s f or r i liate are then ligated with the T4 DNA ligase. The HB101 cells of E. Then the XL-1 Blue are then transformed and the bacteria containing the fragment inserted in the plasmid pC6 or pC4 are identified using, for example, the restriction enzyme analysis.

Chinese hamster ovary cells lacking an active DHFR gene are used for transfection. Five μg of the expression plasmid pC6 or pC4 was co-transfected with 0.5 μg of the pSVneo plasmid using lipofectin (Felgner et al., Up). Plasmid pSV2-neo contains a dominant selectable marker, the T n5 n or T gene encoding an enzyme that confers resistance to a group of antibiotics includes G418. The cells are seeded in an alpha medium minus MEM supplemented with 1 mg / ml of G418. After 2 days, the cells are trypsinized and seeded in the cloning plates of the hybridoma (Greiner, Germany) in alpha medium minus MEM supplemented with 10, 25, or 50 ng / ml of methotrexate plus 1 mg / ml of G418 . After about 10-14 days, individual clones are trypsinised and then seeded in 6-well petri dishes or in 10 ml flasks using different concentrations of methotrexate (50 nM, 100 nM, 200 nM, 400 nM, 800 nM). The growth of the clones at the highest concentrations of methotrexate are then transferred to new 6 well plates containing even higher concentrations of methotrexate (1 uM, 2 uM, 5 uM, 10 nM, 20 nM). The same procedure is repeated until the clones are obtained, which grow at a concentration of 100-200 μm. Expression of METH1 or METH2 is analyzed, for example, by SDS-PAGE and Western blot or by reverse phase HPLC analysis.

Example 11: Construction of the. Removal Mutants N -T ermi nals and / or C- Terminal is The following general method can be used to clone a N-terminal or C-terminal deletion METH1 or METH2 mutant. Generally, two oligonucleotide primers of about 15-25 nucleotides are derived from the desired 5 'and 3' positions of a SEC polynucleotide. ID NO: 1 or SEC. ID NO: 3. The 5 'and 3' positions of the primers are determined based on the fragments of the polynucleotide METH1 or METH2. An initiation codon and a stop codon are added to the 5 'and 3' primers respectively, if necessary, to express the fragment of the METH1 or METH2 polypeptide encoded by the polynucleotide fragment. Preferred fragments of the METH1 or METH2 polynucleotide are those encoding the N-terminal and C-terminal deletion mutants described above in the section "Polynucleotide and Polypeptide Fragments" of the Specification.

Additional nucleotides containing the restriction sites to facilitate cloning of the polynucleotide fragment METH1 or METH2 into a desired vector can also be added to the sequences of the 5 'and 3' primer. The fragment of the polynucleotide METH1 or METH2 is amplified from the genomic DNA or the cDNA clone deposited using the appropriate PCR oligonucleotide primers and conditions discussed here or known in the prior art. Fragments of the METH1 or METH2 polypeptide encoded by the fragments of the METH1 or METH2 polynucleotide of the present invention can be expressed and purified in the same general manner as the full-length polypeptides, although routine modifications may be necessary due to differences in the physical and chemical and physical properties between a particular fragment and the polypeptide of length comp 1 eta.

As a means to exemplify but not limit the present invention, the polynucleotide encoding the D-40 to S-950 fragment of the METH1 polypeptide or the L-20 to L-890 fragment of the METH2 polypeptide is amplified and cloned as follows: A 5 'primer is generated comprising a restriction enzyme site followed by an initiation codon in the structure with the sequence of the polynucleotide encoding the N-terminal portion of the polypeptide fragment starting with D-40 or L-20, respectively. A complementary 3 'primer is generated comprising a restriction enzyme site followed by a stop codon in the structure with the polynucleotide sequence encoding the C-terminal portion of the METH1 or METH2 polypeptide fragment terminating with S-950 or L-890, respectively.

- - The fragment of the amplified polynucleotide and the expression vector are digested with restriction enzymes that recognize the sites in the primers. The digested polynucleotides are then ligated together. The fragment of the METH1 or METH2 polynucleotide is inserted into the restricted expression vector, preferably in a manner that places the coding region of the METH1 or METH2 polypeptide fragment in the 3 'direction from the promoter. The ligation mixture is transformed into competent E. coli cells using standard procedures and as described in the Examples herein. The plasmid DNA is isolated from the resistant colonies and the identity of the cloned DNA is confirmed by restriction analysis, PCR and DNA sequencing.

Example 12: Protein Fusions of METH1 or METH2 The METH1 or METH2 polypeptides are preferably fused to other proteins.

- - These fusion proteins can be used for a variety of applications. For example, fusion of METH1 or METH2 polypeptides to the His-tag, HA-tag, Protein A, IgG, and maltose binding protein domains facilitates purification. (See Example 7, see also EP A 394; 827; Traunecker et al., Na t u r e 33 1: 8 4 - 8 6 (1988)). Similarly, fusion to IgG-1, IgG-3, and albumin increases the half-life in vivo. Nuclear localization signals fused to the METH1 or METH2 polypeptides can target the protein for a specific subcellular localization, whereas covalent homodimers or homodimers can increase or decrease the activity of a fusion protein. Fusion proteins can also generate chimeric molecules that have more than one function. Finally, the fusion proteins can increase the solubility and / or stability of the fused protein compared to the unfused protein. All types of fusion proteins described above can be prepared by modifying the following protocol, which underlines the fusion of a polypeptide to an IgG molecule, or the protocol described in Example 7.

Briefly, the human Fc portion of the IgG molecule can be amplified by PCR, using primers that separate the 5 'and 3' ends of the sequence described below. These primers should also have convenient restriction enzyme sites that will facilitate cloning into an expression vector, preferably a mammalian expression vector.

For example, if pC4 (Accession No. 209646) is used, the Fc portion of human can be ligated into the BamHl cloning site. Note that site 3 'BamHl must be destroyed. Next, the vector containing the Fc portion of human is restricted with BamHl, linearizing the vector, and the polynucleotide METH1 or METH2, isolated by the PCR protocol described in Example 5, is ligated into the BamHI site. Note that the polynucleotide is cloned without a stop codon, otherwise the fusion protein would not be produced.

If the naturally occurring signal sequence is used to produce the secreted protein, pC4 does not need a second signal peptide. Alternatively, if the signal sequence that occurs naturally is not used, the vector can be modified to include a heterologous signal sequence. (See, for example, WO 96/34891).

Fc region of human IgG: GGGATCCGGAGCCCAAA CTTCTGACAAAAC CACACATGCCCA C CGT GC C CAG CAC CT GAAT T CGAGGGT GCAC C GT CAGT CTT CCT CTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACTC CTGAGGTCACATGCGTGGTGGTGGACGTAAGCCACGAAGACCCT GAGGT CAAGTT CAAC TGGTACGTGGAC GGCGTGGAGGTGCATAA TGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACC GT GT GGT CAG CGT CCT CAC CGT CCTGCACCAGGACT GGC T GAAT GGCAAGGAGTACAAGTGCAAGGT CTCCAACAAAG CC CTCC CAAC CCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAG AA-CCACAGGTGTACACCCTGCCCCCATCCCGGGATGAGCTGACC - CGC CGT -AAGAACCAGG CAGCCTGACCTGCCTGGTCAAAGGCTTCTATCC AAGCGACAT GGAGTGGGAGAG CAAT GGGCAGC-CGT GCT CGGAGA ACAACTACAAGACCACGC CTCC CTCC GGACTCCGACGG TTCTTCCTCTACAGCAAGCTCACCGTGGACAAGAGCAGGTGGCA GCAGGGGAACGTCTTCT CAT CGT GAT GCTC GCAT GAGG CT CT GC ACAACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAAA TGAGTGCGACGGCCGCGACTCTAGAGGAT (SEQ ID NO: 85.) Example 1: Produ ction of an An t i c erp o The antibodies of the present invention can be prepared in a variety of methods. (See, the Current Protocols, Chapter 2). For example, cells expressing METH1 or METH2 are administered to an animal for the production of serum containing polyclonal antibodies. In a preferred method, a preparation of the METH1 or METH2 protein is prepared and purified to render it free of naturally occurring contaminants. Such a preparation is introduced into an animal to produce the polyclonal antiserum of higher specific activity.

In the most preferred method, the antibodies of the present invention are monoclonal antibodies (or binding fragments of the protein thereof). Such monoclonal antibodies can be prepared using hybridoma technology. (Kohler et al., Nature 256: 495 (1975), Kohler et al., Eur. J. Immunol., 5: 511 (1976), Kohler et al., Eur. J. Immunol., 6: 292 (1976); Hammerling et al., In: Monoclonal Antibodies and T-Cell Hybridomas, Elsevier, NY, pp. 563-681 (1981) ) . In general, such methods involve immunizing an animal (preferably a mouse) with the METH1 or METH2 polypeptide or, more preferably, with a cell that expresses the secreted METH1 or METH2 polypeptide. Such cells can be cultured in any suitable tissue culture medium; however, it is preferable to culture the cells in Earle-modified Eagle's medium, supplemented with 10% fetal bovine serum (inactivated at approximately 56 degrees C), and supplemented with approximately 10 g / 1 'of non-essential amino acids, approximately 1,000 U / ml penicillin, and approximately 100 ug / ml streptomycin.

Splenocytes from such mice are extracted and fused with a suitable myeloma cell line. Any suitable myeloma cell line can be employed in accordance with the present invention; however, it is preferable to use the myeloma cell line (SP20), available from the ATCC. After fusion, the resulting hybridoma cells are selectively maintained in the HAT medium, and then cloned by limiting dilution as described by Wands et al. (Ga s t r o e n t r o 1 o gy 80: 225-232 (1981).) The hybridoma cells obtained through such selection are then assayed to identify the clones that secrete the antibodies capable of binding to the METH1 or METH2 polypeptide.

Alternatively, additional antibodies capable of binding to the METH1 or METH2 polypeptide can be produced in a two step procedure using antigenic antibodies. Such a method makes use of the fact that the antibodies are antigens by themselves, and therefore, it is possible to obtain an antibody that binds to a second antibody. According to this method, antibodies specific for the protein are used to immunize an animal, preferably a mouse. The splenocytes of such an animal are then used to produce the hybridoma cells, and the hybridoma cells are selected to identify the clones that produce an antibody whose ability to bind to the specific antibody of the METH1 or METH2 protein can be blocked by METH1 or METH2. . Such antibodies comprise antibodies specific to the METH1 or METH2 protein-specific antibody and can be used to immunize an animal to induce the formation of antibodies specific for the additional METH1 or METH2 protein.

It will be appreciated that the Fab and F (ab ') 2 fragments and other fragments of the antibodies of the present invention can be used according to the methods described herein. Such fragments are typically produced by proteolytic cleavage, using enzymes such as papain (to produce Fab fragments) or pepsin (to produce Fab (ab ') 2 fragments). Alternatively, fragments that bind to secreted METH1 or METH2 proteins can be produced through the application of recombinant DNA technology or through chemical synthesis.

For the in vivo use of the antibodies in humans, the "humanized" chimeric monoclonal antibodies are preferable. Such antibodies can be produced using genetic constructs derived from the hybridoma cells that produce the monoclonal antibodies described above. Methods for producing chimeric antibodies are known in the art. (See, for review, Morrison, Science 229: 1202 (1985); Oi et al., Bio Echniques 4: 214 (1986); Cabilly et al., US Patent No. 4,816,567; Taniguchi et-al., EP 171496 Morrison et al., EP 173494; Neuberger et al., WO 8601533; Robinson et al., WO 8702371; Boulianne et al., Nature 312: 643 (1984); Neuberger et al., Nature 314: 268 (1985)) .

Example 14: Production of the METHl or METH2 Pro tein for High Performance Selection Tests The following protocol produces a supernatant containing the METH1 or METH2 polypeptide to be tested. This supernatant can then be used in the Selection Tests described in Examples 16-23.

First, dilute a solution of Poly-D-Lysine (644 587 Bo eh ringe r-Ma n nh and im) (1 mg / ml in PBS) 1:20 in PBS (p / o calcium or magnesium 17-516F B i owh itta ke r) for a working solution of 50 ug / ml). Add 200 ul of this solution to each well (26-well plates) and incubate at room temperature for 20 minutes. Be sure to distribute the solution on each well (note: you can use a 12-channel pipette with tips on each of the channels). The aspiration of the Poly-D-Li-sine solution will be carried out and it will be rinsed with 1 ml of PBS (Phosphate-buffered Saline Solution). The PBS should remain in the well until just before placing the cells in plates and the plates should be coated with poly-lysine for a time of about two weeks.

The 293T cells are plated (no cells are placed in P + 20) at 2 x 10 5 cells / well in .5 ml of DMEM (Eagle's Medium Modified with Dulbecco) (with 4.5 G / L glucose and L-glutamine (12-604F Biowhi tt aker)) / 10% FBS inactivated by heat (14-503F B io wh i 11 a ke r) / 1 x Penstrep (17-602E Biowhittaker). The cells are allowed to grow overnight.

The next day, they are mixed together in a sterile basin solution: 300 ul of Lipofectamine (18324-012 - -Gibco / BRL) and 5 ml of Optimem I (31985070 Gibco / BRL) / 96-well plate. With a small volume multi-channel pipette, aliquots of approximately 2 ug of an expression vector containing a polynucleotide insert, produced by the methods described in Examples 10-12, are added to a 96-well round bottom plate. , appropriately labeled. Using a multi-channel pipette, add 50 μl of the mixture of L ip or f e c t ami n / Op t imem to each well. The pipette moves so that the liquid can be mixed properly. It is incubated at room temperature for 15-45 minutes. After approximately 20 minutes, a multi-channel pipette is used to add 150 ul of Optimem I to each well. As a control, a plate of the DNA vector that lacks an insert must be transfected into each set of t r an s f e c ts.

Preferably, the transfection should be carried out by a labeling team following the steps mentioned below. Through labeling equipment, takes cells half the time, and does not put them in PBS for long. First, Person A aspirates the medium from four plates of 26 cell wells, and Person B rinses each well with 5-1 mL of PBS. Then Person A aspirates the PBS rinse, and Person B, using a 12-channel pipette with the tips in the alternate channels, adds 200 μl of the DNA / L complex ip or fe ct ami na / Op t imem I the first wells, then to the alternative wells, to each row on the 24-well plate. It is incubated at 37 degrees C for 6 hours.

While the cells are incubated, the appropriate medium is prepared, either 1% BSA in DMEM with penstrep lx, or the HGS CHO-5 medium (116.6 mg / L CaCl2 (anhydrous); 0.00130 mg / L CuS04 -5H20, 0.050 mg / L of Fe (N03) 3-9H20, 0.417 mg / L of FeS04-7H20, 311.80 mg / L of K c 1, 28.64 mg / L of M g C 12, 48.84 mg / L of MgS0 6995.50 mg / L of NaCl, 2400.0 mg / L of NaHC? 3, 62.50 mg / L of - -NaH2P04-H2?, 71.02 mg / L of Na2HP0, 4320 mg / L of ZnS0 -7H2 ?;, .002 mg / L of Arachidonic Acid, 1022 mg / L of Cholesterol, .0 * 70 mg / L of DL- to 1 fa -To co f er o 1-Acetate, 0.0520 mg / L of Linoleic Acid, 0.010 mg / L of Acid Linoleic, 0.010 mg / L of Miristic Acid, 0.010 mg / L of Oleic Acid, 0.010 mg / L of Palmic Acid, 0.010 mg / L of Palmitic Acid, 100 mg / L of F-68 Pluronic, 0.010 mg / L of Acid Stearic, 2.20 mg / L of Tween 80, 4551 mg / L of D-Glucose, 130.85 mg / mL of L-Alanine, 147.50 mg / mL of L-Ar ginine - HC 1, 7.50 mg / mL of L-Asparagine- H2? 6.65 mg / ml L-aspartic acid 29.56 mg / ml of L -Cysteine-2HCl-H2 ?; 31.29 mg / ml of L-Cysteine-2HCl; 7.35 mg / ml L-Glutamic Acid; 365.0 mg / ml of L-Glutamine; 18.75 mg Glycine; 52.48 mg / ml of L-Histidine-HCl-H2O; 106.97 mg / ml L-Isoleucine; 111.46 mg / ml L-Leucine; 163.75 mg / ml L-Lysine HCL; 32.34 mg / ml L-Methionine; 68.48 mg / ml L-Phenylalanine; 40.0 mg / ml L-Proline, 26.25 mg / ml L-Serine; 101.05 mg / ml L-Threonine; 19.22 mg / ml L-Tryptophan; 91.79 -mg / ml of L-Trirosina-2Na-2H2 ?; and 99.65 mg / ml L-Valine; 0.0035 mg / L of Biotin; 3.24 mg / L of D-Ca Pantothenate; 11.78 mg / L Choline Chloride; 4.65 mg / L of Folic Acid; 15.60 mg / L of i-Inositol; 3.02 mg / L of Niacinamide; 3.00 mg / L of Pyridoxal HCL; 0.031 mg / L of Pyridoxine HCL; 0.319 mg / L of Riboflavin; 3.17 mg / L Thiamine HCL: 0.365 mg / L Thymidine; 0.680 mg / L of Vitamin B12; 25 mM of the HEPES Shock Absorber; 2.39 mg / L of Na Hypoxanthine; 0.105 mg / L of Lipoic Acid; 0.081 mg / L Putrescine Sodium-2HCl; 55.0 mg / L of Sodium Pyruvate; 0.0067 mg / L of Sodium Selenite; 20 uM Ethanolamine; 0.122 mg / L Ferric Citrate; 41.70 mg / L of Methyl-B-Cyclodextrin forming complexes with Linoleic Acid; 33.33 mg / L of Methyl-B-Cyclodextrin forming complexes with Oleic Acid; 10 mg / L of Methyl-B-Cyclodextrin forming complexes with Retinal Acetate. The osmolarity is adjusted to 327 mOsm) with 2 mm of glutamine and penstrep lx. 100 gm of BSA (81-068-3 Bayer) are dissolved in 1 L of DMEM to form a -10% BSA solution). The medium is filtered and 50 ul are collected for the endotoxin test in 15 ml of conical poly styrene.

The transfection reaction is terminated, preferably by the labeling equipment, at the end of the incubation period. Person A aspirates the transfection medium, while Person B adds 1.5 ml of the appropriate medium to each well. It is incubated at 37 degrees C for 45 or 72 hours depending on the medium used: 1% BSA for 45 hours or CHO-5 for 72 hours.

On day 4, a 300-ul multichannel pipette, an aliquot of 600 ul in a 1-ml well plate, and the rest of the supernatant in a 2-ml-deep well are used. The supernatant from each well is then used in the assays described in Examples 16-23.

It is specifically understood that when the activity is obtained from any of the assays described below using a supernatant, the activity originates either from the METH1 or METH2 polypeptide directly (eg, as a secreted protein) or through expression induced by METH1 or METH2 of other proteins, which are then secreted into the supernatant. Thus, the invention further provides a method for identifying the protein in the supernatant characterized by an activity in a particular assay.

Example 15 Construction of the GAS Reporter Cons A signal transduction pathway involved in the differentiation and proliferation of cells is called the Jaks-STAT pathway. The proteins activated in the Jaks-STAT pathway are linked to the "GAS" elements of the gamma activation site or to the interferon-sensitive response element ("ISRE"), located in the promoter of several genes. The binding of a protein to these elements alters the expression of the associated gene.

- - The GAS and ISRE elements are recognized by a class of transcription factors called transducers and activators of the transcription signal or "STAT". There are six members of the STAT family. Statl and Stat3 are present in many types of cells, as is Stat2 (in response to IFN-alpha which is very widespread). Stat4 is very restricted and is not found in many types of cells although it has been found in class I of T helper cells, the cells after treatment with IL-12. Stat5 was originally called the mammary growth factor, but has been found at higher concentrations in other cells that include myeloid cells. It can be activated in tissue culture cells by many cytokines.

STATs are activated to translocate from the cytoplasm to the nucleus after tyrosine phosphorylation by a set of kinases known as the Janus Kinase ("Jaks") family. The Jaks represent a distinct family of soluble tyrosine kinases and include Tyk2, Jakl, Jak2, and Jak3. These kinases show significant sequence similarity and are catalytically inactive generally in the remaining cells.

The Jaks are activated by a wide range of receivers summarized in the following Table. (Adapted from the review by Schidler and Darnell, Ann. Rev. Biochem. 64: 621-51 (1995)). A family of the cytokine receptor, capable of activating the Jaks, is divided into two groups: (a) Class 1 includes the receptors for IL-2, IL-3, IL-4, IL-6, IL-7, IL -9, IL-11, 1L-12, 11-15, Epo, PRL, GH, G-CSF, GM-CSF, LIF, CNTF, and thrombopoietin; and (b) Class 2 includes IFN-a, IFN-g, and IL-10. Class 1 receptors share a conserved portion of cysteine (a set of four conserved clteinins and a tryptophan) and a WSXWS portion (a proxial membrane region encoding Trp-Ser-Xxx-Trp-Ser (SEQ ID NO: 82)).

- Thus, when linked to a receiver, the Jaks are activated, which in turn activate the STATs, which then translocate and link to the GAS elements. This entire process is directed in the Jaks-STAT transduction pathway.

Therefore, the activation of the Jaks-STAT pathway, reflected by the GAS link or the ISRE element, can be used to indicate the proteins involved in the proliferation and differentiation of cells. For example, the growth factors are known and the cytokines activate the Jaks-STAT pathway. (See Table below). Thus, using the GAS elements linked to the reporter molecules, the activators of the Jaks-STAT pathway can be identified.

- - To construct a promoter element containing GAS, which is used in the Biological Assays described in Examples 16-17, a PCR-based strategy was employed to generate a GAS-SV40 promoter sequence. The 5 'primer contains four tandem copies of the GAS-binding site-found in the IRF1 promoter and was previously shown to bind to the STATs after induction with a range of cytokines (Rothman et al., Imm un t 1: 457-468 (1994)), although other GAS or ISRE elements may be used instead. The 5 'primer also contains 18 bp of the sequence complementary to the SV40 early promoter sequence and is flanked by an Xhol site. The sequence of the primer 50 is: 5 ': GCGCCTCGAGATTT CCCCGAAATCTAGATTT CCCCGAAATG ATTTCCCCGAAATGATTT CCCCGAAATAT CT GC CAT CT CAAT TA G: 3' (SEQ ID NO: 86).

The primer in the di rece ion is complementary to the SV40 promoter and is flanked by a Hind III site: 5 ': GCGGCAAGCTTTTTGCAAAGCCTAGGC: 3' (SEQ ID NO: 87).

Amplification is performed with PCR using the SV40 promoter pattern present in plasmid B-gal: promoter obtained from Clontech. The resulting PCR fragment is digested with Xhol / Hind III and subcloned into -BLSK2 - (S t ra t agene). Sequencing primers with forward and reverse confirms that the insert contains the following sequence: 5 ': CTCGAGATTTCCCCGAAAT CTAGATTT CCC GGC CGAAATGATTT CCCCGAAATGATTTCCCCGAAATATCTGCCATCTCAATTAGTCA GCAACCATAGTCCCGCCCCTAACTCCGCCCATCCCGCCCCTAAC TCCGCCCAGTTCCGCCCATTCTCCGCCCCAT TGACTAAT TT TTTTTATTTATGCAGAGGCCGAGGCCGCCTCGGCCTCTGAGCTA TTCCAGAAGTAGTGAGGAGGCTTTTTTGGAGGCCTAGGCTTTTG CAAAAAGCT 3' (SE ID NO. 88).

With this GAS promoter element linked to the SV40 promoter, a GAS: SEAP2 reporter construct is genetically engineered. Here, the reporter molecule is a secreted alkaline phosphatase, or "SEAP". Clearly, however, any reporter molecule can be used in place of SEAP, in this or any of the other Examples. Well-known reporter molecules that can be used in place of SEAP include chloramphenicol acetyltransferase (CAT), luciferase, alkaline phosphatase, B-galactoside idasa, green fluorescent protein (GFP), or any detectable protein - by an antibody.

The previous sequence confirmed that the synthetic promoter element GAS-SV40 was subcloned into the p S EAP-P vector obtained from Clontech using HindIII and Xhol, effectively replacing the SV40 promoter with the amplified promoter element GAS.-SV40, for create the GAS-SEAP vector. However, this vector does not contain a neomycin resistance gene, and therefore, is not preferred for mammalian expression systems.

Thus, to generate stable mammalian cell lines expressing the GAS-SEAP reporter, the GAS-SEAP cassette or cartridge is removed from the GAS-SEAP vector using Sali and Notl, and inserted into a vector in the main structure containing the gene of resistance to neomycin, such as pGFP-1 (Clontech), using these restriction sites in the multiple cloning site, to create the GAS - S EAP / Ne o vector. Once this vector is transfected into the mammalian cells, this vector can then be used as a reporter molecule to bind GAS as described in Examples 16-17.

Other constructs can be fabricated using the above description and replacing the GAS with a different promoter sequence. For example, the construction of reporter molecules containing the promoter sequences NFK-B and EGR are described in Examples 18 and 19. However, many other promoters can be substituted using the protocols described in these Examples. For example, the promoters of SRE, IL-2 NFAT, or Osteocalcin can be substituted, alone or in combination (eg, GAS / NF-KB / EGR, GAS / NF-KB, I1-2 / NFAT, or NF- KB / GAS). Similarly, other cell lines can be used to test the activity of the reporter construct, such as HELA (epithelial), HUVEC (endothelial), Reh (B cell), Saos-2 (osteoblast), HUVAC (aortic), or Car di oiocitos.

Example 16: High Efficiency Selection Test for T Cell Activity The following protocol is used to assess the activity of T cells in METH1 or METH2 determining if the supernatant of METH1 or METH2 proliferates and / or differentiates the T cells. The activity of the T cells is evaluated using the construct GAS / SEAP / Neo produced in Example 15. Thus, the factors that increase the activity of SEAP indicate the ability to activate the transduction pathway of the Jaks-STATS signal. The T cells used in this assay are Jurkat T cells (Accession No. ATCC TIB-152), although Molt-3 cells (Accession No. ATCC CRL-1552) and Molt-4 cells ( Accession No. ATCC CRL-1582).

Jurkat T cells are lymphoblastic Thl CD4 + helper cells. To generate stable cell lines, - approximately 2 million Jurkat cells are transfected with the GAS-SEAP / neo vector using DMRIE-C (Life Technologies) (the transfection procedure is described below). The transfected cells are seeded at a density of approximately 20,000 cells per well and the resistant strains are selected at 1 mg / ml of genticin. The resistant colonies are expanded and then tested for their response to the increased concentrations of interferon gamma. The dose response of a selected clone is demonstrated in this way.

Specifically, the following protocol will generate enough cells for 75 wells containing 200 ul of cells. Thus, either it is scaled, or it is done in multiples to generate enough cells to multiply 96-well plates. Jurkat cells are maintained in RPMI + 10% serum with 1% Pen-Strep. 2.5 mis of OPTI-MEM are combined (Life Technologies) with 10 ug of the plasmid DNA in a T25 flask. 2.5 ml of OPTI-MEM containing 50 ul of DMRIE-C are added and incubated at room temperature for 15-45 minutes.

During the incubation period, the cell concentration is counted, the required number of cells are separated (10 per transfection), and resuspended in OPTI-MEM to a final concentration of 10 cells / ml. Then add 1 ml of 1 x 107 cells in OPTI-MEM to a T25 flask and incubate at 37 degrees C for 6 hours. After incubation, 10 ml of RPMI + 15% serum are added.

The stable reporting lines Jur ka t: GAS - SEAP are maintained in RPMI + 10% serum, 1 mg / ml Genticin, and 1% Pen-Strep. These cells are treated with the supernatants containing the METH1 or METH2 polypeptides or the METH1 or METH2-induced polypeptides as produced by the protocol described in Example 14.

On the day of treatment with the supernatant, the cells should be washed and resuspended in fresh RPMI + 10% serum to a density of 500,000 cells per ml. The exact number of cells required will depend on the number of supernatants to be selected or separated. For a 96-well plate, approximately 10 million cells are required (for 10 plates, 100 million cells).

The cells are transferred to a triangular container, to supply the cells in a 96-well dish, using a 12-channel pipette. Using a 12-channel pipette, 200 ul of cells were transferred into each well (therefore, 100,000 cells are added per well).

After all the plates have been seeded, 50 ul of the supernatants are transferred directly from the 96-well plate containing the supernatants to each well using a 12-channel pipette. In addition, a dose of exogenous interferon gamma (0.1, 1.0, 10 ng) is added to wells H9, H10, and Hll to serve as additional positive controls for the ens ay The 96-well dishes containing the Jurkat cells treated with the supernatant are placed in an incubator for 48 hours (note: this time is variable between 48-72 hours). Then, 35 ul samples are transferred from each well to an opaque 96-well plate using a 12-channel pipette. Opaque plates should be covered (using selofen covers) and stored at -20 degrees C until the SEAP assays are performed according to Example 20. Plates containing the remaining treated cells are placed at 4 degrees C and serve as a source of material to repeat the test in a specific well if desired.

As a positive control, 100 Units / ml of interferon gamma that is known to be active to Jurkat T cells can be used. After a 30-fold induction, the positive -controls are typically observed in the wells.

Example 17: High Efficiency Selection Test Identifying the Myeloid Activity The following protocol is used to assess the myeloid activity of METH1 or METH2 by determining whether METH1 or METH2 proliferates and / or differentiates myeloid cells. The activity of the myeloid cells is assessed using the GAS / SEAP / Neo construct produced in Example 15. Thus, the factors that increase the SEAP activity indicate the ability to activate the transduction pathway of the Jaks-STAT signals. The myeloid cells used in the assay are the U937, a cell line of p r e -mo not c i t o, although TF-1, HL60, or KG1 can also be used.

To transfect T rans in the U937 cells with the GAS / SEAP / Neo construct produced in Example 15, a DEAE-Dex trano method is used (Kharbanda et al., -1994, Cell Growth &Differentiation 5 : 259-265). First 2xl0e7 of the U937 cells are harvested and washed with PBS. U937 cells are usually grown in RPMI 1640 medium containing 10% heat inactivated fetal bovine serum (FBS) supplemented with 100 units / ml penicillin and 100 mg / ml streptomycin.

The cells are then suspended in 1 ml of the 20 mM Tris-HCl buffer (pH 7.4) containing 0.5 mg / ml DEAE-Dextran, 8 ug of the GAS-SEAP2 plasmid DNA, 140 mM NaCl, 5 mM KCl. , Na2HPO -7H20 375uM, 1mM MgCl2, and 675uM CaCl. Incubate at 37 degrees C for 45 minutes.

The cells are washed with RPMI 1640 medium containing 10% FBS and then resuspended in 10 ml of the complete medium and incubated at 37 degrees C for 36 hours.

Stable GAS-SEAP / U937 cells are obtained by growing the cells in 400 ug / ml of G418. The free medium of -G418 is used for routine growth but from one to two months, the cells should be re-grown in 400 ug / ml of G418 for coupling the steps.

These cells are tested by harvesting 1x10 cells (this is sufficient for the assay of ten 96-well plates) and washed with PBS. The cells are suspended in 200 ml of the growth medium described above, with a final density of 5x10 cells / ml. Plates of 200 ul of cells are formed per well in the 96-well plate (or 1x10 cells / well). 50 ul of the supernatant prepared by the protocol described in Example 14 are added. They are incubated at 37 degrees C for 48 to 72 hours. As a positive control, 100 Units / ml of interferon gamma that is known to activate U937 cells can be used. A thirty-fold induction is typically observed in the positive control wells. The SEAP assay of the supernatant is carried out according to the protocol - described in Example 20.

Example 18: High Efficiency Selection Test Identifying Neuronal Activity When cells undergo differentiation and proliferation, a group of genes is activated through the many different signal transduction pathways. One of these genes, EGR1 (early growth response gene I), is induced in several types of tissues and cells after activation, the EGR1 promoter is responsible for such induction. Using the EGR1 promoter linked to the reporter molecules, the activation of the cells can be assessed by METH1 or METH2.

In particular, the following protocol is used to assess neuronal activity in PC12 cell lines. It is known that PC12 cells (rat orchid phenotype cells) proliferate and / or differentiate by activation with a number of - mitogens, such as TPA (tetr adenol phorbol acetate), NGF (cell growth factor). nerves), and EFG (epidermal growth factor). The expression of the EGR1 gene is activated during this treatment. Thus, by stable transfection of the PC12 cells with a construct containing an EGR promoter linked to the SEAP reporter, the activation of the PC12 cells can be assessed by METH1 or METH2.

The EGR / SEAP reporter construct can be assembled by the following protocol. The sequence of the EGR-1 promoter (-633 to +1) (Sakamoto K et al., On co gene e 6: 8 61 - 8 1 1 (1991)) can be amplified by PCR from human genomic DNA using the following primers: GCGCTCGAGGGATGACAGCGATAGAACCCCGG-3 'SEC ID NO 89 5 'GCGAAGCTTCGCGACTCCCCGGATCCGCCTC-3' (SEQ ID NO: 90) - - Using the vector GAS / SEAP / Neo produced in Example 15. The amplified product of EGR1 can then be inserted into this vector. The GAS / SEAP / Neo vector is linearized using the restriction enzymes Xho I / H and nd I I I, eliminating GAS / SV40 material. The amplified product EGR1 is restricted with these same enzymes. The vector and the EGR1 promoter are ligated.

To prepare 96-well plates for cell culture, add two more of a coating solution (1:30 dilution of type I collagen (Upstate Biotech Inc. CAT # 08-115) in 30% ethanol (sterilized by filtration )) by a 10 cm plate or by a 50 ml well of the 96 well plate, and allowed to air dry for 2 hours.

PC12 cells are grown routinely in RPMI-1640 medium (Bio Whittaker) containing 10% horse serum (JRH BIOSCIENCES, Cat. # 12449-78P), 5% fetal bovine serum inactivated by heat (FBS) supplemented with LO 0 - uni dade s / ml of penicillin and 100 ug / ml of streptomycin in a 10 cm tissue culture patch re - revered. They are made from one to four cuts every three to four days. The cells are removed from the plates by scraping and resuspended with shaking up and down by means of a pipette for more than 15 times.

Transfection of the EGR / SEAP / Neo construct in PC12 using the Lipofectamine protocol is described in Example 14. Stable EGR-SEAP / PC12 cells are obtained by growing the cells in 300 ug / ml of G418. The G418-free medium is used for routine growth but each one to two months, the cells should be re-grown in 300 μg / ml of G418 to be coupled to the steps.

To test the neuronal activity, a 10 cm plate with cells of approximately a confluent of 70 to 80% - is selected by removing the previous medium. The cells are washed once with PBS (Saline buffered with phosphate). The cells are then left without food in medium with low amount of serum (RPMI-1640) containing 1% horse serum and 0.5% FBS with antibiotics) overnight.

The next morning, the medium is removed and the cells are washed with PBS. Cells are scraped from the plate, cells are suspended in wells in 2 ml of medium with low serum content. The number of cells is counted and more medium is added with low serum content until reaching a final cell density of 5xl05 cells / ml. 200 ul of the cell suspension is added to each well of the 96-well plate (equivalent to lxlO5 c é 1 u la s / po z o). 50 ul of the supernatant produced by Example 14, 37 degrees C for 48 to 72 hours are added. As a positive control, a known growth factor can be used to activate the PC12 cells through EGR, such as 50 ng / ul of the Neuronal Growth Factor (NGF). For a fifty-fold induction of SEAP as typically observed in positive control wells. The SEAP assay of the supernatant is performed according to E j emp lo 20.

Example 19: High Efficiency Selection Test for T Cell Activity NF-KB (Nuclear Factor KB) is a treatment factor activated by a wide variety of agents including the IL-1 Inflammatory cytokines and TNF, CD30 and CD40, the 1 infot oxi na-a 1 fay and lyfotoxin-beta , by exposure to LPS or thrombin, and by expressing certain viral gene products. As a transcription factor, NF-KB regulates the expression of genes involved in the activation of immune cells, the control of apoptosis. (NF-KB seems to protect cells from apoptosis), the development of B and T cells, antiviral and antimicrobial responses, and responses to multiple pressure.

Under non-stimulated conditions NF-KB is retained in the cytoplasm with I-KB (KB inhibitor). However, after the stimulation, the I-KB degrades, causing the NF-KB to migrate to the nucleus, thus activating the transcription of the target genes. The target genes are activated by NF-KB which includes IL-2, IL-6, GM-CSF, ICAM-1 and MHC class 1.

Due to their central role and the ability to respond to a range of stimuli, reporter constructs using the NF-KB promoter element are used to select the supernatants produced in Example 14. Activators or inhibitors of NF-KB should be useful in the treatment of ailments. For example, NF-KB inhibitors could be used to treat those conditions related to the acute or chronic activation of NF-KB, such as rheumatoid arthritis.

To construct a vector containing the NF-KB promoter element, a PCR-based strategy is employed. The primer in the 5 'direction contains four tandem copies of the NF-KB binding site (GGGGACTTT CCC) (SEQ ID NO: 91), 18 bp of the sequence complementary to the 5' end of the SV40 early promoter sequence, and It is flanked with an Xhol site: 5 ': GCGGCCTCGAGGGGACTTTCCCGGGGACTTTCCGGGGACTT TCCGGGACTTTCCATCCTGCCATCTCAATTAG: 3 'SEC. ID NO: 92) The leader in the complementary direction to the 3 'end of the SV4 promoter, and flanked by a Hind III site: 5 ': GCGGCAAGCTTTTTGCAAAGCCTAGGC: 3' (SEQ ID NO: 93) - PCR amplification is performed using the SV40 promoter pattern present in plasmid pB-ga 1: pr omot or obtained from Clontech. The resulting PCR fragment is digested with Xhol and Hind III and subcloned in BLSK2- (Stratagene). Sequencing with primers T7 and T3 confirms that the insert contains the following sequence: 5 ': CTCGAGGGGACTTTCCCGGGGACTTTCCGGGGACTTTCCGG GACTTTCCATCTGCCATCTCAATTAGTCAGCAACCATAGTCCCG CCCCT AC C C CGC CCG CCC CATC CTAACT CCGCCCAGT T C CGC CGG CCT CCATTCTCCGCCCCATGGCTGACTAATTTTTTTTATTTATGCAG AGGC CGAGGCCGCCT GAGCTAT T CT C CAGAAGTAGT GGAGGCTTTTTTGGAGGCCTAGGCTTTTGCAAAAAGCTT GA 3' (SEQ ID NO. 88) Next, the minimal promoter element SV40 present in the promoter plasmid pSEAP2 (Clontech) is replaced with this NF-KB / SV40 fragment using Xhol and HindIII. However, this vector does not contain a gene for 'resistance to neomycin, and is therefore not preferred for mammalian expression systems.

- - To generate stable mammalian cell lines, the NF-KB / SV40 / S EAP cassette is removed from the previous NF-KB / SEAP vector using the SalI and NotI restriction enzymes, and inserted into a vector containing resistance to neomycin. In particular, the NF-KB / S V40 / S EAP cassette is inserted into pGFP-1 (Clontech), replacing the GFP gene, after restricting pGFP-1 with SalI and Not I. _ Once the NFKB / SV40 / SEAP / Neo vector is formed, the stable Jurkat T cells are created and maintained according to the protocol described in Example 16. Similarly, the method for testing the supernatants with these Jurkat T cells Stable is also described in Example 16 as a positive control, exogenous TNF alpha (0.1, 1, 10 ng) is added to wells H9, H10, and Hll, whereby a typical activation is observed 5 to 10 times.

- - Ex empl o 20 En sa yo pa ra l a A c t i i da SEA P As a reporter molecule for the assays described in Examples 16-19, SEAP activity is assayed using the Tropix Pho Spho-1 i gh t kit (Cat. BP-400) according to the following general procedure. The Tropix Ph or s ph o - 1 i gh t equipment supplies the Dilution, Test, and Reaction Buffers used below.

A spout is primed with the 2.5x Dilution Damper and are added 15 ul of the 2.5x dilution buffer in Optiplates containing 35 ul of a supernatant. The plates are sealed with a plastic sealant and incubated at 65 degrees C for 30 minutes. They separate the Optiplates avoiding a heating not a fo rme.

The samples are cooled to room temperature for 15 minutes. The spout is emptied and primed with the test buffer. 50 ml of the 4-Assay Buffer is added and incubated at room temperature for 5 minutes. The spout is emptied and primed with the Reaction Shock Absorber (see table below). 50 of the Reaction Buffer are added and incubated at room temperature for 20 minutes. Since the intensity of the chemiluminescent signal is time dependent, and it takes approximately 10 minutes to read 5 plates in a luminometer, 5 plates should be treated at a time and started in the second set 10 minutes later.

The unit of relative light in the luminometer is read. The H12 is set as a reference point and the results are printed.

An increase in the number of cases indicates the reporting activity.

Formulation of the Reaction Shock Absorber # of plates Diluent of buffer Rxn (ml) CSPD (ml) "__." .. ". " 11 65 3.25 12 70 • 3.5 13 75 3.75 14 80 4 15 85 4.25 16 90 4.5 17 -. 17 - 95 4.75 18 100 5 19 105 5.25 20 110 5.5 21 115 5.75 22 120 6 23 125 6.25 24 130 6.5 25 135 6.75 26 140 7 27 145 7.25 28 150 7.5 29 155 7.75 30 160 8 31 165 8.25 32 170 8.5 33 175 8.75 34 180 9 35 185 9.25 36 190 9.5 37 195 9.75 38 200 10 39 205 10.25 40 210 10.5 41 215 10.75 42 220 11 43 225 11.25 44 230 11.5 45 235 11.75 46 240 12 47 245 12.25 48 250 12.5 49 255 12.75 50 260 13 Example 21: High Efficiency Selection Trials that Identify the Changes in the Small Cell Concentration and the Permeability of the Membrane It is known that the binding of a receptor alters the intracellular levels of small molecules, such as calcium, potassium, sodium and pH, as well as alters the potential of the membrane. These alterations can be measured in an assay to identify supernatants that bind to the receptors of a particular cell. Although the following protocol describes an assay for calcium, this protocol can be easily modified to detect changes in potassium, sodium, pH, membrane potential, or any other small molecule that is detectable by a fluorescent probe.

The following tests use the Imaging Plate Reader Fluo r orne t r i cas ("FLIPR") to measure changes in fluorescent molecules (Molecular Probes) that bind to small molecules. Clearly, any fluorescent molecule that detects a small molecule can be used in place of the fluorescent calcium molecule, fluo-3 is used here.

For adherent cells, sowing cells at 10,000-20,000 cells / well in a black 96-well plate Co-star is made with a clear background. The plate is incubated in a CO2 incubator for 20 hours. The adherent cells are washed twice in the Biotek scrubber with 200 ul of HBSS (Hank's Balanced Salt Solution) leaving 100 ul of the buffer after the final wash.

A stock solution of 1 mg / ml fluo-3 is made with 10% DMSO pluronic acid DMSO. To load the cells with fluo-3, 50 ul of 12 ug / ml of fluo-3 is added to each well. The plate is incubated at 37 degrees C in a CO2 incubator for 60 - 4 minutes. The plate is washed four times in the Biotek washer with HBSS leaving 100 ul of the buffer.

For non-adherent cells, the cells are subjected to centrifugation of the culture medium. The cells are resuspended at 2-5x106 / ml with HBSS in a 50 ml conical tube. Add 4 ul of 1 mg / ml of fluo-3 in solution with DMSO and 10% pluronic acid to each ml of cell suspension. The tube is then placed in a water bath at 37 degrees C for 30-60 minutes. Cells are washed twice with HBSS, resuspended at lxlO6 cells / ml, and supplied to a microplate, 100 ul / well. The plate is centrifuged at 1000 rpm for 5 minutes. The plate is then washed in Denley's CellWash washer with 200 ul, followed by an aspiration step to 100 ul of final volume.

For a non-cell-based assay, each well contains a fluorescent molecule, such as fluo-3. The supernatant is added to each well, and a change in fluorescence is detected.

To measure the fluorescence in the intracellular calcium, the FLIPR is adjusted to the following parameters: (1) The gain of the system is 300-800 mW; (2) The exposure time is 0.4 seconds; (3) The F / holding chamber is F / 2; (4) Excitation is 488 nm; (5) The emission is at 530 nm; and (6) The addition of the sample is 50 ul. The increased emission at 530 nm indicates an extracellular signaling event caused by a molecule, either METH1 or METH2 or a molecule induced by METH1 or METH2, which results in an increase in the intracellular Calcium concentration.

Example 22: High Efficiency Selection Test and Identify the Activity of the Ti Kinase Kinase The protein tyrosine kinases (PTK) represents a diverse group of cytoplasmic and transmembrane kinases. Within the RPTK receptor tyrosine kinase protein group are the receptors for a range of metabolic and mitogenic growth factors including PDGF, FGF, EGF, NGF, HGF and the insulin receptor subfamilies. In addition, there is a large RPTK family for which the corresponding ligand is unknown. The ligands for RPTK include mainly the small secreted proteins, but also the proteins of the extracellular matrix and those that bind to the membrane.

The activation of RPTK by the ligands involves the dimerization of the receptor mediated by the ligand, which results in the t r an s fo s f or i the ion of receptor subunits and the activation of cytoplasmic tyrosine kinases. Tyrosine kinases include the receptor associated with tyrosine kinases of the src family (eg, src, yes, lck, lyn, fyn) and the cytosolic tyrosine kinases and linked to non-receptors, such as the Jak family, members of which mediate the transduction of the signal generated by the cytokine superfamily of the receptors (for example, I nter 1 eu cines, In t er fer one s, GM-CSF, and Leptin).

Due to the wide range of known factors capable of stimulating tyrosine kinase activity, the identification of either METH1 or METH2 or a molecule induced by METH1 or METH2 is capable of activating the signal transduction pathways of tyrosine kinase. wide interest. Therefore, the following protocol is designed to identify such molecules capable of activating the pathways of tyrosine kinase signal transduction.

The target cells are seeded (e.g., primary keratinocytes) at a density of approximately 25,000 cells per well in 96-well Loprodyne Silent Selection Plates, purchased from Nalge Nunc (Naperville, IL). The plates are sterilized with two 30-minute rinses with 100% ethanol, rinsed with water and dried overnight. Some plates are coated for 2 hours with 100 ml of type I collagen of cell culture grade (50 mg / ml), gelatin (2%) or polylysine (50 mg / ml), all of which is purchased from Sigma Chemicals (St Louis, MO) or 10% Matrigel purchased from Becton Dickinson (Bedford, MA), or calf serum, rinsed with PBS and stored at 4 degrees C. Cell growth in these plates is tested by planting 5,000 cells / well in the growth medium and cell number is indirectly quantified through the use of alamarBlue as described by the manufacturer Alamar Biosciences, Inc. (Sacramento, CA) after 48 hours. Becton Dickinson's Falcon # 3071 plate liners (Bedford, MA) are used to cover the Loprodyne Silent Selection Plates. Falcon Microtest III cell culture plates can also be used in some proliferation experiments.

To remove the extracts, sow the A431 cells in the nylon membranes of the Loprodyne plates (20,000 / 200 ml / well) and culture overnight in a complete medium. The cells are grown by incubation in a serum-free basal medium for 24 hours. After 5-20 minutes with the EGF treatment (60 ng / ml) or 50 ul of the supernatant produced in Example 14, the medium was removed and 100 ml of the extraction buffer ((20 mM HEPES pH 7.5, 0.15 M NaCl) , Triton X-100 1%, SDS 0.1%, Na3V04 2 M, Na4P207 2 mM and a cocktail of protease inhibitors (# 1836170) obtained from Boehringer Mannheim (I ndi anap or 1 is, IN) were added to each well and the plate was shaken on a rotary shaker for 5 minutes at 4 ° C. The plate was then placed in a vacuum transfer set and the extract was filtered through the bottom of the 0.45 mM membrane of each well using vacuum The extracts were placed in a 96-well test plate at the bottom of the vacuum equipment and immediately placed on ice.To obtain the extracts clarified by centrifugation, the content of each well, after solubilization with detergent during 5 minutes, it was removed and centrifuged for 15 m inutes at 4 degrees C at 16,000 x g.

The filtered extracts were tested to verify the levels of tyrosine kinase activity. Although many methods for detecting tyrosine kinase activity are known, a method is disclosed.

Generally, the tyrosine kinase activity of a supernatant is evaluated by determining its ability to phosphorylate a tyrosine residue on a specific substrate (a biotinylated peptide). Biotinylated peptides that can be used for these purposes include PSK1 (corresponding to amino acids 6-20 of the cell division kinase cdc2-p34) and PSK2 (which corresponds to amino acids 1-7 of gastrin). Both peptides are substrates for tyrosine kinase range and there are 28 available from Boehringer Mannheim.

The tyrosine kinase reaction is adjusted by adding the following components in the following order. First, add 10 ul of the 5 uM Biotinylated Peptide, then 10 uL of ATP / Mg2 + (5 mM ATP / 50 mM MgC12), then 10 ul of the 5x Assay Buffer (40 M imidazole hydrochloride, pH 7.3, beta- glycerof osf ato 40 mM, EGTA 1 mM, MgCl2 100 mM, MnCl2 5 mM, 0.5 mg / ml BSA 0.5), then add 5 ul of Sodium Vanadate (1 mM), and then 5 ul of water. The components are mixed gently and the reaction mixture is preincubated at 30 degrees C for 2 minutes. The reaction is started by adding 10 μl of the control enzyme or the filtered supernatant.

The reaction of the tyrosine kinase assay is then terminated by adding 10 ul of EDTA 120 mm and the reactions are placed on ice.

The tyrosine kinase activity is determined by transferring 50 ul of the aliquot of the reaction mixture to a microtiter plate module (MTP) and incubating at 37 degrees C for 20 minutes. This allows the e s t r ep t to review the 96-well plate and associate with the biotinylated peptide. The MTP module is washed with 300 ul / well of PBS four times. Next, 75 ul of anti-phosphotyrosine antibody conjugated with horseradish peroxidase (a n t i - P-T and r-POD (0.5 u / ml)) is added to each well and incubated at 37 degrees C for one hour. A good washing is carried out as indicated above.

A 100 μl of the peroxidase substrate solution (Boehringer Mannheim) is added and incubated at room temperature for at least 5 minutes (up to 30 minutes). The absorbance of the sample at 405 nm is measured using the ELISA reader. The level of peroxidase activity is quantified using the ELISA reader and the level of tyrosine kinase activity is reflected.

Example 23: High Efficiency Selection Test that Identifies Phosphorylation Activity With an alternative and / or potential complement to the assay of the tyrosine kinase activity described in Example 22, an assay that detects the activation (phosphorylation) of the main intracellular signal transduction intermediates can also be used. For example, as described below, a particular assay can detect the tyrosine phosphorylation of the Erk-1 and Erk-2 kinases. However, phosphorylation of other molecules, such as Raf, JNK, p38 MAP, Map Kinase Kinase (MEK), MEK Kinase, Src, Muscle Specific Kinase (MuSK), IRAK, Tec, and Janus, as well as any other Phosphoserine molecule, phosphotyrosine, ofos fo tronon, can be detected by substitution of these molecules by Erk-1 or Erk-2 in the following assay.

Specifically, test plates are prepared by coating the wells of a 9.6-well ELISA plate with 0.1 ml of the G protein (1 ug / ml) for 2 hours at room temperature (RT). The plates are rinsed with PBS and blocked with 3% BSA / PBS for 1 hour at room temperature. The G protein plates are then treated with 2 commercial monoclonal antibodies (100 ng / well) against Erk-1 and Erk-2 (1 hour at room temperature) (Santa Cruz Biotechnology). (To detect other molecules, this step is easily modified by replacing a monoclonal antibody with any of the molecules described above). After 3-5 rinses with PBS, the plates are stored at 4 degrees C until they are used.

A431 cells are seeded 20,000 / well in a 96-well Loprodyne filter plate and are grown overnight in a growth medium. The cells are left un-fed for 48 hours in the basal medium (DMEM) and swallowed with EGF (6 ng / well) or 50 ul of the supernatants obtained in Example 14 for 5-20 minutes. The cells are then solubilized and the extracts are filtered directly to the test plate.

After incubation with the extract for 1 hour at room temperature, the wells are rinsed again. As a positive control, a commercial preparation of the MAP kinase MAP kinase (10 ng / well) is used in place of the A431 extract. The plates are then treated with a commercial polyclonal antibody (rabbit) (1 μg / ml) which specifically recognizes the phosphorylated epitope of the Erk-1 and Erk-2 kinases (1 hour at room temperature). This antibody is biotinylated by standard procedures. The bound polyclonal antibody is then quantified by successive incubations with the fluorescence enhancement reagent Eur opium-is t rep avidin and Europium in the Wallac DELFIA instrument (fluorescence with time resolution). An increased fluorescent signal on the background indicates phosphorylation by METH1 or METH2 or a molecule induced by METH1 or METH2.

Example 24: Method to Terminate Alterations in the METHl or METH 2 Gene RNA isolated from whole families or individual patients presenting a phenotype of interest (such as a condition is isolated) Then cDNA is generated from these RNA samples using protocols known in the art (See, Sambrook). The cDNA is then used as a template or standard for PCR, employing primers surrounding the regions of interest in SEQ ID NO: 1. Suggested PCR conditions consist of 35 cycles at 95 degrees C for 30 seconds; seconds at 52-58 degrees C; and 60-120 seconds at 70 degrees C, using buffer solutions described in Sidransky, D. et al., Science 252: 106 (1991).

The PCR products are then sequenced using primers labeled at their 5 'end with the T4 polynucleotide kinase, using SequiTherm Polymerase (Epicenter Technologies). The edges of the intron-exon of selected exons of METH1 or METH2 are also determined and the products of the genomic PCR are analyzed to confirm the results. PCR products suspected of containing mutations in METH1 or METH2 are then cloned and sequenced to validate the results of direct sequencing.

The METH1 or METH2 PCR products are cloned into vectors with a T-tail as described in Holton, T.A. and Graham, M.W., Nu cl e i c A c d s R e s c a r 1 9: 1 1 5 6 (1991) and sequenced with T7 polymerase (United States Biochemical). Affected individuals are identified by mutations in METH1 or METH2 that are not present in unaffected individuals.

Genomic rearrangements are also observed as a method to determine alterations in the METH1 or METH2 gene. The isolated genomic clones are translated with 5 'triphosphate of d i g or x i ge n i nde s ox i - u r i di n a (Boehringer Manheim), and the FISH treatment is performed as described in Johnson Cg. et al., Methods Cell Biol. 35: 73-99 (1991). Hdization with the tagged probe is performed using a large amount of human cot-1 DNA for hdization specific to the genomic site of METH1 or METH2.

The chromosomes are coptratified with 4,6-diami no-2-f in i 1 gone 1 and propidium iodide, producing a combination of C and R bands. The aligned images for accurate map formation are obtained using a filter set triple band (Chroma Technology, Brattleboro, VT) in combination with a camera with cooled charge coupled device (Pho t orne trics, Tucson, AZ), and variable excitation wavelength filters. (Johnson, Cv. Et al., Gen e t. An a l. T e ch. App l. 8: 1 5 (1991)). The collection of the image, the analysis and the measurements of the fractional length _ of the chromosome are made using the ISee Graphic Program System. (Inovision Corporation, Durham, NC). Chromosomal alterations of the METH1 or METH2 genomic region (hdized by the probe) are identified as insertions, deletions, and t r ans 1 ocac i one s. These alterations of METH1 or METH2 are used as diagnostic markers for an associated condition.

Example 25: Method to Detect the Abnormal Levels of METH1 or METH2 in a Biological Movement The METH1 or METH2 polypeptides can be detected in a biological sample and if an increased or decreased level of METH1 or METH2 is detected, this polypeptide is a marker for a particular phenotype. Detection methods are numerous, and therefore, it is understood that someone with ordinary skill in the art can modify the following assay to adjust it to their particular needs.

For example, ELISA assays of an antigenic protein are used to detect METH1 or METH2 in a sample, preferably a biological sample. The wells of a microtitre plate are coated with antibodies specific for METH1 or METH2, at a final concentration of 0.2 to 10 ug / ml. The antibodies are either monoclonal or polyclonal and are produced by the method described in Example 13. The wells are blocked so as to reduce the non-specific binding of METH1 or METH2 to the wells.

The coated wells are then incubated for > 2 hours at room temperature with a sample containing METH1 or METH2. Preferably, serial dilutions of the sample should be used to validate the results. The plates are then washed three times with deionized or distilled water to remove the unbound or bound METH1 or METH2.

Next, 50 ul of the phosphatase conjugate is added to 1 ca 1 i na - an specific titre, at a concentration of 25-400 ng, and incubated for 2 hours at room temperature. The plates are again washed three times with deionized or distilled water to remove the unbound conjugate. 75 ul of the solution of the phosphate substrate of 4-me t i 1 umbe 1 i f e r i 1 o (MUP) or p-nitrophenyl phosphate (NPP) to each well and incubated for 1 hour at room temperature. The reaction is measured by a microtiter plate reader. A standard curve is prepared, using serial dilutions of a control sample, and the concentration of the METH1 or METH2 polypeptide on the X axis is plotted. (logarithmic scale) and fluorescence or absorbance on the Y axis (linear scale). The concentration of METHl or METH2 in the sample is interpolated using the standard curve.

Example 26: Formulation of Pol ipép ti do The composition of METHl or METH2 will be formulated and dosed in a manner consistent with good medical practice, taking into account the clinical conditions of the individual patient (specifically the side effects of treatment with the METH1 or METH2 polypeptide alone), the delivery site, the administration method, administration schedule, and other factors known to practitioners. The "effective amount" for the purposes of the present invention is thus determined by such considerations As a general proposition, the total pharmaceutically effective amount of METH1 or METH2 administered parenterally per dose will be in the range of about 1 ug / kg / day to 10 mg / kg / day of the patient's body weight, although, as noted previously, this will be subject to the discretion of the therapy. More preferably, this dose is at least 0.01 mg / kg / day, and more preferably for humans it is between approximately 0.01 and 1 mg / kg / day for the hormone. If given continuously, METHl or METH2 is typically administered at a dose rate of about 1 ug / kg / hour to about 50 ug / kg / hour, either through 1-4 injections per day or through continuous subcutaneous infusions, per example, using a mini-pump. An intravenous bag solution can also be used. The length of treatment needed to observe the changes and the next treatment interval for the responses seems to vary depending on the desired effect.

The pharmaceutical compositions containing METH1 or METH2 of the invention can be administered orally, rectally, parenterally, intracistically, intravaginally, intraperitoneally, topically (as powders, ointments, gels, drops or transdermal patches), buccally, or as a oral or nasal spray. The "pharmaceutically acceptable carrier" refers to a solid, semi-solid or liquid, non-toxic filler, diluent, encapsulating material or auxiliary formulation of any type. The term "parenteral" as used herein refers to the modes of administration that include intravenous, intramuscular, intraperitoneal, i n t r a s t n a 1, subcutaneous injection and infusion, and infusion.

METH1 or METH2 is also appropriately administered by sustained release systems. Suitable examples of sustained release compositions include polymer matrices in the form of shaped articles, e.g., films or microcapsules. Sustained-release matrices include polylactides (U.S. Patent No. 3,773, 919, EP 58 581), the copolymers of L-glutamic acid and gamma-eti 1-L-g 1 ut ama to (Sidman, U. et al., Biopolymers 22: 541-556 (1983)), poly (methacrylate) of 2 - hi dr ox ieti 1 o) (R. Langer et al., J. Biomed, Mater. Res. 15: 161-211 (1981), and R. Langer / Chem. Tech. 12: 98-105 ( 1982)), ethylene vinyl acetate (R. Langer et al.) Or acid or 1 i - D - (-) - 3 - hi droxib utiri co (EP 133,988). Sustained-release compositions also include METH1 or METH2 polypeptides entrapped in liposomes. Liposomes containing the METH1 or METH2 polypeptides are prepared by methods known per se: DE 3,218,121; Epstein et al. , Proc. Natl. Acad. Sci. USA 52: 3688-3692 (1985); Hwang et al. , Proc. Natl. Acad. Sci. USA 77: 4030-4034 (1980); EP 52,322; EP 36,676; EP 88,046; EP 143,949; EP 142,641; Japanese Patent Application 83-118008; U.S. Patent Nos. 4,485,045 and 4,544,545; and EP 102,324. Ordinarily, the liposomes are of a small size unilamellar type (approximately 200-800 Angstroms) in which the lipid content is greater than about 30 mole percent cholesterol, the selected ratio being adjusted for optimal secreted polypeptide therapy.

For parenteral administration, in one embodiment, METH1 or METH2 is generally formulated by mixing it to the desired degree purity, in an injectable unit dosage form (solution, suspension, or emulsion), with a pharmaceutically acceptable carrier, i.e., one that be non-toxic to the people who receive them in the doses and concentrations used and be compatible with other ingredients of the formulation. For example, the formulation preferably does not include oxidizing agents and other compounds that are known to be harmful to the polypeptides.

In general, the formulations are prepared by contacting the METHl or METH2 uniformly and intimately with liquid carriers or finely divided solid carriers. Then, if necessary, the product is formed into the desired formulation. Preferably, the carrier is a parenteral carrier, more preferably a solution that is isotonic with the blood of the person receiving it. Examples of such carriers include water, saline, Ringer's solution, and dextrose solution.

Non-aqueous vehicles such as fixing oils and ethyl oleates are also useful here, as well as the first ones.

The carrier suitably contains small amounts of additives such as substances that improve isotonicity and chemical stability. Such materials are non-toxic to the people who receive them in the dosages and concentrations employed, and include buffers such as phosphate, citrate, succinate, acetic acid, and other organic acids or their salts; antioxidants such as ascorbic acid; polypeptides of low molecular weight (less than about ten residues) polypeptides, for example, polyarginine or tripeptides; proteins, such as serum albumin, gelatin, or immunoglobulins; hydrophilic polymers such as polyvinylpyrrolidone; amino acids, such as glycine, glutamic acid, aspartic acid, or arginine; monosaccharides, disaccharides, and other carbohydrates including cellulose or its derivatives, glucose, mannose, or dextrins; chelating agents such as EDTA; sugar alcohols such as mannitol or sorbitol; counterions such as sodium; and / or nonionic surfactants such as polysorbates, poloxamers, or PEG.

METH1 or METH2 is typically formulated in such vehicles at a concentration of about 0.1 mg / ml to 100 mg / ml, preferably 1-10 mg / ml, at a pH of about 3 to 8. It will be understood that the use of certain excipients, carriers, "or prior stabilizers will result in the formation of the salts of the polypeptides.

METHl or METH2 used for therapeutic administration can be sterile. Sterility is easily supplemented by filtration through 0.2 micron membranes). The therapeutic compositions of the polypeptide are generally placed in a container-containing a sterile access port, for example, an intravenous solution bag or a vial having a pierceable portion by hypodermic injection needle.

The METH1 or METH2 polypeptides are ordinarily stored in single or multiple dose containers, eg sealed ampoules or ampoules, as an aqueous solution or as a lyophilized formulation for reconstitution. As an example of a lyophilized formulation, the 10 ml ampoules are filled with 5 ml of the filtered, sterile 1% (w / v) aqueous METH1 or METH2 polypeptide solution, and the resulting mixture is lyophilized. The infusion solution is prepared by reconstituting the lyophilized METH1 or METH2 polypeptide using Water for bacteriostatic injection.

The invention also provides a pharmaceutical pack or kit comprising one or more containers filled with one or more of the ingredients of the pharmaceutical compositions of the invention. Associated with such containers may include a notice or instruction in the form prescribed by a governmental agency that regulates the manufacture, use or sale of pharmaceutical or biological products, which notifies or information reflects the approval by the agency of the manufacture, use or sale for human administration. In addition, METH1 or METH2 can be used in conjunction with other therapeutic compounds.

Example 27: Method to Treat the Decreased Levels of METHl or METH2 The present invention relates to a method for treating an individual in need of a decreased level of METH1 or METH2 activity in the body, comprising, administering to said individual a composition comprising a therapeutically effective amount of the METH1 or METH2 antagonist. . Preferred antagonists for use in the present invention are antibodies specific for METH1 or METH2.

In addition, it will be appreciated that conditions caused by a decrease in the level of expression or normal of METH1 or METH2 in an individual can be treated by the administration of METH1 or METH2, preferably in the secreted form. Thus, the invention also provides a method for treating an individual in need of increased level of METH1 or METH2 polypeptide comprising administering to such an individual a pharmaceutical composition comprising an amount of METH1 or METH2 to increase the level of activity of METH1 or METH2. in such an individual.

For example, a patient with decreased levels of the METH1 or METH2 polypeptide receives a daily dose of 0.1-100 ug / kg of the polypeptide for six consecutive days. Preferably, the polypeptide is in the secreted form. The exact details of the dosing scheme, based on the administration and formulation, are provided in E 26.

Example 28: Method to Treat Increased Levels of METHl or METH2 The present invention relates to a method for treating an individual in need of an increased level of METH1 or METH2 activity in the body, comprising, administering to said individual a composition comprising a therapeutically effective amount of METH1 or METH2 or a agonist thereof.

Antisense technology is used to inhibit the production of METH1 or METH2. This technology is an example of a method for decreasing levels of the METH1 or METH2 polypeptide, preferably a secreted form, due to a variety of etiologies such as cancer.

For example, a patient diagnosed with abnormally increased levels of METHl or METH2 receives the antisense polynucleotides administered intravenously at 0.5, 1.0, 1.5, 2.0 and 3.0-45 -mg / kg / day for 21 days. This treatment is repeated after a rest period of 7 days if the treatment is well tolerated. The formulation of the antisense polynucleotide is provided in Example 26.

Example 29: Method for Treatment Using Genetic Therapy - Ex Vi A method of genetic therapy transplants fibroblasts, which are capable of expressing the METH1 or METH2 polypeptides, in a patient. Generally, fibroblasts are obtained from a subject by skin biopsy. The resulting tissue is placed in a tissue culture medium and separated into small pieces. The small portions of the tissue are placed on a wet surface of a tissue culture flask, approximately ten pieces are placed in each flask. The flask is turned under down, closed tightly and left at room temperature overnight. After 24 hours at room temperature, the flask is inverted and the tissue portions remain fixed to the bottom of the flask and the fresh medium is added (for example, Ham's F12 medium, with 10% FBS, penicillin and streptomycin). ). The flasks are then incubated at 37 degrees C for about a week.

At this time, fresh media is added and it is subsequently loaded every several days. After two additional weeks of culture, a monolayer of fibroblasts emerges. The monolayer is trypsinized and placed in larger flasks.

PMV-7 (Ki rs chmeier, PT et al., DNA 7: 219-25 (1988)), flanked by the long terminal repeats of Moloney murine sarcoma virus is digested with EcoRI and HindIII and subsequently treated with phosphatase Veal intestine The linear vector is fractionated in agarose gel and purified, using glass beads.

The cDNA encoding METH1 or METH2 can be amplified using PCR primers corresponding to the 5 'and 3' end sequences respectively as set forth in Example 5. Preferably, the 5 'primer contains an EcoRI site and the primer 3 'includes a HindIII site. Equal amounts of the linear backbone structure of the Moloney murine sarcoma virus and the amplified EcoRI and HindIII fragment are added together in the presence of T4 DNA ligase. The resulting mixture is maintained under conditions suitable for ligation of the two fragments. The ligation mixture is then used to transform the HB101 bacteria, which are plated onto agar containing kanamycin for the purpose of confirming that the vector contains METH1 or METH2 properly inserted.

Amphotropic packaging cells pA317 or GP + aml2 are grown in tissue culture to a confluent density in Dulbecco's Modified Eagle's Medium (DMEM) with 10% calf serum (CS), penicillin and streptomycin. The MSV vector containing the METH1 or METH2 gene is then added to the medium and the packaging cells are transduced with the vector. The packaging cells now produce infectious viral particles that contain the METH1 or METH2 gene (packaging cells are now referred to as producer cells).

The fresh medium is added to the transduced producer cells, and subsequently, the medium is harvested from a 10 cm plate of the confluent producer cells. The spent medium, which contains the infectious viral particles, is filtered through a millipore filter to eliminate the producer cells that may have remained there and this medium is then used to infect the fibroblast cells. The medium is removed from a sub-confluent plate of fibroblasts and rapidly replaced with the medium of the produced cells. This medium is eliminated and replaced with fresh medium.If the virus titer is high, then virtually all fibroblasts will be infected and no selection will be required.If the titer is very low, then it is necessary to use a retroviral vector that has a selectable marker, such as neo or his Once the fibroblasts have been efficiently infected, the fibroblasts are analyzed to determine if the METH1O METH2 protein was produced.

The fibroblasts genetically engineered in this way are then transplanted to the host or host, either alone or after having grown them to confluence in my cytodexpositories.

Example 30: Method for Treatment Using Genetic Therapy I n Vi v o Another aspect of the present invention is to use the in vivo gene therapy methods to treat conditions, diseases and conditions. The method of gene therapy refers to the introduction of naked nucleic acid (DNA, RNA, and antisense DNA or RNA) to METH1 or METH2 sequences in an animal to increase or decrease the expression of METH1 or METH2 polypeptide. The METH1 or METH2 polynucleotide can be operably linked to a promoter or any other genetic elements necessary for the expression of METH1 or METH2 polypeptide by the target tissue. Such gene therapy and delivery techniques and methods are known in the art, see, for example, WO 90/110902, WO 98/11779; U.S. Patent No. 5693622, 5705151, 5580859; Tabata H. Et al. (1997) Cardiovasc. Res. 35 (3): 470-479, Chao, J et al. (1997) Pha rma col. Beef. 35 (6): 517-522, Wolff J.A. (1997) Neuromuscul. Disord. 7 (5): 314-318, Schwartz, B. et al. (1996) Gene Ther. 3 (5): 405-411, Tsurumi Y. et al. (1996) Circulation 94 (12): 3281-3290 (incorporated herein by reference).

The polynucleotide -METH1 or METH2 constructs can be delivered by any method that delivers injectable materials to the cells of an animal, such as injection into the interstitial spaces of the tissues (heart, muscle, skin, lung, liver). , intestine and the like). The constructs of the METH1 or METH2 polynucleotide can be delivered in a pharmaceutically acceptable liquid or aqueous carrier.

The term "naked" polynucleotide, DNA or RNA, refers to sequences that are free of any delivery vehicle that acts to assist, promote or facilitate entry to cells, which include viral sequences, viral particles, liposome formulations, lipofectin or precipitating agents and the like. However, polynucleotides METH1 and METH2 can also be supplied in liposome formulations (such as those taught in Felgner P.L. et al. (1995) Ann. NY Acad. Sci. 772: 139 and Abdallah B. et. al (1995) Biol. Cell 85 (1): 1-1) can be prepared by methods well known to those skilled in the art.

The constructs of the METH1 or METH2 polynucleotide vector used in the gene therapy method are preferably constructs that will not be integrated into the genome of the host or host nor will they contain sequences that allow replication. Any strong promoter known to those skilled in the art can be used to drive DNA expression. Unlike other techniques of genetic therapies, a major advantage for introducing naked nucleic acid sequences into target cells is the transient nature of the synthesis of the polynucleotide in cells. Studies have shown that non-replicative DNA sequences are introduced into the cells to provide production of the desired polypeptide for periods of up to six months.

- - The METH1 or METH2 polynucleotide construct can be delivered in the interstitial space of tissues within an animal, including the muscles, skin, brain, lung, liver, spleen, bone marrow, thymus, heart, heart, lymph, blood, bone, cartilage, pancreas, kidney, bladder, stomach, intestine, testes, ovaries, uterus, rectum, nervous system, eyes, glands, and connective tissue. The interstitial space of the tissues comprises the intercellular tissue, the matrix of mu c op or 1 isacid between the reticular fibers of the tissues of the organs, the elastic fibers in the walls of the containers or chambers, the collagen fibers of the fibrous tissues, or those of the same matrix within the muscle cells that cover the connective tissues or in the final parts of the bones. Similarly, the space occupied by the plasma of the circulation and the lymphatic fluid of the lymphatic channels. The supply to the interstitial space of muscle tissue is preferred for reasons discussed below. It can be conveniently supplied by injection into the tissues comprising these cells. They are preferably delivered and expressed in persistent, non-dividing cells, which are differentiated, although delivery and expression can be achieved in less fully differentiated or undifferentiated cells, such as, for example, blood stem cells or skin fibroblasts. The cells of the muscle groups are particularly competent in their ability to absorb and express the polynucleotides.

For the injection of the polynucleotide METHl or METH2 naked, an effective dose amount of DNA or RNA will be in the range of about 0.05 g / kg per body weight to approximately 50 mg / kg per body weight. Preferably the dose will be from about 0.005 mg / kg to about 20 mg / kg and more preferably from about 0.05 mg / kg to about 5 mg / kg. Of course, as the technician with ordinary skills will appreciate, this dosage will vary according to the site of the tissue of the injection. The effective and appropriate dose of the nucleic acid sequence can easily be determined by those skilled in the art and may depend on the condition to be treated and the route of administration. The preferred route of administration is the parenteral injection route in the interstitial spaces of the tissues. However, other parenteral routes may also be used, such as inhaling an aerosol formulation particularly for delivery to the lungs or bronchial tissues, throat or mucous membranes of the nose. In addition, naked METH1 or METH2 polynucleotide constructs can be delivered to the arteries during angioplasty by the catheter used in the procedure.

The dose-response effects of the polynucleotide METH1 or METH2 injected into the muscle vi is determined as follows.

The template DNA of METH1 or METH2 suitable for the production of the mRNA encoding the METH1 or METH2 polypeptide is prepared according to a standard recombinant DNA methodology. The DNA of the template or pattern, which can be circular or linear, is used either as naked DNA or complexed with liposomes. The muscles of the quadriceps of mice are then injected with various amounts of the standard or template DNA.

Female and male Balb / C mice from five to six weeks of age are anesthetized by intraperitoneal injection with 0.3 ml of 2.5% Avertin. An incision of 1.5 cm is made in the anterior legs, and the quadriceps muscle is directly visualized. The METH1 or METH2 standard DNA is injected into 0.1 ml of the carrier in a 1 cm3 syringe through a 27 gauge needle for one minute, approximately 0.5 cm from the distal injection site of the muscle in the knee and approximately 0.2 cm depth. A suture is placed over the injection site for future ligation, and the skin is closed with stainless steel forceps.

After an appropriate incubation time (for example, 7 days) the muscle extracts are prepared by excising the complete quadriceps. Each fifth 15-μm cross-section of the muscles of the individual quadriceps is stained by the muscle for the expression of the METH1 or METH2 protein. A time course for the expression of the METH1 or METH2 protein can be done in a similar manner except that the quadriceps of different mice are harvested at different times. The persistence of METH1 or METH2 DNA in the muscle after injection can be determined by blot analysis, Southern after body weight prepare cellular DNA and HIRT supernatants from injected and control mice. The results of previous experimentation in the mice can be used to extrapolate suitable doses and other treatment parameters in humans and other animals using the naked DNA of METH1 or METH2.

It will be clear that the invention can be practiced other than that described particularly in the description and the previous examples.

Numerous modifications or variations of the present invention are possible in light of the foregoing teachings and, therefore, are within the scope of the appended claims.

The full description of all publications (including patents, patent applications, articles of publications, laboratory manuals, books, or other documents) are cited here and incorporated by reference.

LIST OF SEQUENCES < 110 > Iruela-Arispe, Luisa Hastings, Gregg A. Ruben, Steven M. < \ 2C > Polynucleotides and Polypeptides of Methl and Meth2 < 130 > 1488.107FCQ2 < 140 > < 141 > < 150 > 60 / 072,298 < 151 > 1998-01-23 < 1S0 > 60 / 098,539 < 151 > 1998-08-28 < 160 > 93 170 > PatentIn Ver. 2.0 < 210 > 1 < 211 > 3S61 < 212 > DNA < 213 > Homo sapiens < 220 > < 221 > CDS < 222 > (1) .. (28S3) < 22C > < 221 > IT IS NOT INSURANCE < 222 > . { 3095) < 223 > It can be any nucleic acid < 220 > < 221 > IT IS NOT INSURANCE < 222 > . { 3248) < 223 > It can be any nucleic acid < 220 > < 221 > IT IS NOT INSURANCE < 222 > (3255) < 223 > It can be any nucleic acid < 220 > < 222 IS NOT INSURANCE < 222 > (3261) < 223 > It can be any nucleic acid < 40C > 1 ate ggg aac gcg gag cgg gct ccg ggg tet cgg age ttt ggg ccc qta 48 Met Gly Asn Ala Glu Arg Ala Pro Gly Ser Arg Ser Fr.ß Gly Pro Val 1 5 10; = ccc acg ctg ctg ctg etc gcc gcg gcg cta ctg gcc ccr cg ga ger; 96 Pro Tnr Leu Leu Leu Leu Ala Ala Ala Leu Leu Ala Va- Ser Asp Ai; 20 25 3C etc ggg cgc ccc tcc gag gag gac gag gag cta gtg gt ccg gag ctg 144 Leu Giy Arg Pro Ser Giu Glu Asp Glu Glu Leu Val Val Pro Glu Lßu 35 40 45 gag cgc gcc ccg gga ca ggg acc acg cgc etc cgc etc falls gcc ttt 192 Glu Arg Wing Pro Gly His Gly Thr Thr Arg Leu Arg Le His Wing Phe 50 55 60 gac cag cg gg cg cg gg cg cg cg cg gac age age ttt tg gcg 240 Asp Gin Gin Leu Asp Leu Glu Leu Arg Pro ñsp Ser Ser Phe Leu Ala 65 70 75 80 ccc ggc tc acg etc cag aac gtg ggg cgc aaa rec ggc tcc gag acg 2B8 Pro Giy Phe Thr Leu Gln Asn Val Glv Arg Lys Ser Gi.- Ser Glu Thr 85 90 95 ccg ctt csg gaa acc gac ctg gcg fall tgc ttc tac tcc ggc acc gtg 336 Pro Leu Pro Glu Thr Asp Leu Wing His Cys Phe Tyr Ser Gly Thx: Val 100 IOS 110 aat ggc gat ccc age tcg gct gcc gcc etc age etc tcc gag ggc gtg 384 ñsn Cly Asp Pro Being Wing Wing Wing Leu Being Leu Cys Glu Gly Val 115 120 125 cgc g =: c gcc rtc tac ctg ggg gag gcg tat tre ate cag ccg ctg 432 Arg Gly Wing Phe Tyr Leu Leu Gly Glu Wing Tyr Pne lie Glr. Pro Lßu 130 135 140 ccc gcc gcc age gag cgc etc gcc acc gcc gcc cca ggg gag aag ccg 480 Pro? La Wing Ser Glu Arg Leu Wing Thr Wing Wing Pro Gly Glu Lyb Pro 145 150 155 160 ccg gca cca cta cag ttc falls etc ctg cgg cgg aat cgc cag ggc gac 528 Pro Wing Pro Leu Gln Phe Kis Leu Leu Arg Arg Asn Ar Gln Gly Asp 165 170 175 gta ggc ggc acg tgc ggg gtc gtc gac gac gac ccc ccg ccg act ggg 576 Val Gly Gly Thr Cys Gly Val Val Asp A = p Glu Pro Arg Pro Thr Gly 180 1B5 190 aaa cq gag acc gaa gac gag gac gaa ggg act gag cgc gag gac gaa 624 Lys = > l Glu Thr Glu Asp Glu Asp Glu Gly Thr Glu Gly Glu Asp Glu 195 200 2; S ggg = t cag tgg tcg ccg cag gac ccg gca ctg ca g =; gt cag C12 Gly Pro Gln Trp Pro Pro Gln As-p Pro Wing Leu Glp Gly Val Gly Gln 210 215 220 ccc for gga act ga age ata aga aag aag cga ttt gtg ccc agt ca 720 Pro Thr Gly Thr Gly Ser lie Arg Lys Lys Arg Phe Vai Ser Ser 225 225 235 240 cgc taz gtg gaa acc atg ctt gtg gca gac cag tcg atg gca gaa ttc 768 Arg Tyr Val Glu Thr Met Leu Val Wing Asp Gln Ser Met Wing Glu Phe 245 250 25S falls ggc agt ggt cta aag cat tac ctt etc acg ttg ttt tcg gtg gca 816 fiis Gly Ser Gly Leu Lys His Tyr Lsu Leu Thr Leu P e Ser Val Wing 260 265 270 gcc aga ttg tac aaa falls ccc age att cgt aat tea gtt age ctg gtg 864 Wing Arg Leu Tyr Lys His Pro Ser lie Arg Asn Sex Val Ser Leu Val 275 280 285 gtg gtg aag ate ttg gtc ate fall gat gaa cag aag ggg ccg gaa gtg 912 Val Val Lys lie Leu Val He Kis Asp Glu Gln Lys Gly Pro Glu Val 29C 295 300 acc tcc aat gct gcc etc act ctg cgg aac ttt tgc aac tgg cag aag 960 Thr Ser Asn Ala Ala Leu Thr Leu Arg Asn Phe Cys Asn Trp Gln Lys 305 310 315 320 cag falls aac cea ccc agt gac cgg gat gca gag falls tat gac here gca 1008 Gln His Asn Pro Pro Ser Asp Arg Asp Ala Glu His Tyr Asp Thr Wing 325 330 335 ate ctt ttc acc aga cag gac ttg tgt ggg tcc cag here tgt gat act 1056 lie Leu Phe Thr Arg Gln Asp Leu Cys Gly Ser Gln Thr Cys Asp Thr 340 345 350 ctt ggg atg gct gat gtt gga act gtg tgt gat ccg age aga age tgc 1104 Leu Gly Met Wing Asp Vai Gly Thr Val Cys Asp Pro Ser Arg Ser Cys 355 360 365 tcc gtc ata qaa gat gat ggt tta cact gct gcc ttc acc here gcc cat 1152 Ser Val He Glu Asp Asp Gly Leu Gln Wing Wing Phe Thr Thr Wing HIS 370 375 380 gaa tta ggc falls gtg ttt aac atc cca cat gat gat gca aag cag tgt 1200 Glu Leu Gly Hxs Val Phe Asn Ket Pro His Asp Asp Ala Lys Gln Cys 385 390 395 400 gcc age ctt aat ggt gtg aac cag gat tcc falls atg atg gcg tea atg 12 8 Ala Ser Leu Asn Gly Val Asn Glp Asp Ser Met Met Met Wing Met Met 405 410 415 ctt tcc aac ctg gac falls age cag ect tgg tet ect tgc agt gcc tac 1296 Leu Ser Asn Leu Asp His Ser Gln Pro Trp Ser Pro Cys Ser Ala Tyr 420 425. 30 atg att here tea ttt ctg gat aat ggt cat ggg gaa tgt tg atg gac 1344 Met He Thr Ser Phe Leu Asp Asn Gly His Gly Glu Cys Leu Met Asp 435 440 445 aag ect cag aat ccc ata cag etc cca ggc gat ect ect cgc acc tcg 1392 Lys Pro Gln A3n Pro He Gln Leu Pro Gly Asp Leu Pro Gly Thr Ser 450 455 460 tac gat gcc aac cgg cag tgc cag ttt here ttt ggg gag gacc tcc aaa 1440 Tyr Asp Wing Asn Arg Gln Cys Gln Phe Thr Phe Gly Glu Asp Ser Lys 465 470 475 4S0 falls tgc ct gat gca gcc age here tgt age acc ttg tgg tgt acc ggc 1488 His Cys Pro Asp Ala Ala Ser Thr Cys Ser Thr Leu Trp Cys Thr Gly 485 490 495 acc tet ggt ggg gtg ctg gtg tgt caa acc aaa falls ttc ccg tgg gcg 153S Thr Ser Gly Gly Val Leu Val Cys Gin Thr Lys Hia Phe Pro Trp Wing 500 505 510 gat ggc acc age tgt gga gaa ggg aaa tgg tgt ate aac ggc aag tgt 1534 Asp Gly Thr Ser Cys Gly Glu Gly Lys Trp Cya He Asn Gly Lys Cys 515 520 525 gtg aac aaa acc gac aga aag cat ttt gat acg ect ttt eat gga age 1632 Val Asn Lys Thr Asp Arg Lys His Phe Asp Thr Pro Phe His Gly Ser 530 535 540 tgg gga atg tgg ggg ect tgg gga gac tgt tcg aga acg tgc ggt gga 1680 Trp Gly Met Trp Gly Pro Trp Gly Asp Cys Ser Arg Thr Cys Gly Gly 5J5 550 555 560 gga gtc cag tac acg atg agg gaa tgt gac aac cca gtc cca aag aat 1728 Gl Val Gln Tyr Thr Het Ar? Glu Cys Asp Asn Pro Val Pro Lys Asn 565 570 575 gga ggg aag tac tgt gaa ggc aaa cga gtg cgc tac aga tec tgt aac 1776 Gly Gly Lys Tyr Cys Glu Gly Lys Arg Val Arg Tyr Arg Ser Cys Asn 580 585 590 ctt gag gac tgt cca gac aat aat gga aaa acc ttt aga gag gaa caa 1824 Leu Glu Asp Cys Pro Asp Asn Asn Gly Lys Thr Phe Arg: Glu Glu Gln 595 600 605 tgt gaa gca falls aac gag ttt tea aaa gct tcc ttt ggg agg ggg ect 1872 Cys Giu Wing His Asn Glu Phe Ser Lys Wing Wing Phe Giy Ser Gly Pro SIO 615 620 gcg gtg gag tgg att ccc aag tac gct ggc gtc tea cca aag gac agg 1S20 Wing Val Glu Trp He Pro Lys Tyr Wing Gly Val Ser Pro Lys Asp Arg 625 630 635"640 tgc aag etc tgc ca gcc aaa ggc att ggc tc gtc gtc ttc gtt ttg 1968 Cys Lys Leu He Cys Gln Ala Lys Gly He Gly Tyr Phe? -re Vai Leu 645 650 655 cag ccc aag gtt gta gat ggt act cca tgt age cca gat ccc acc tet 2016 Gln Pro Lys Val Val Asp Gly Thr Pro Cys Ser Pro Asp Ser Thr Ser 660 665 670 gtc gtg gtg ca gg cag tgt gta aaa gct ggt tgt gat cgc ate ata 206 4 Val Cys Val Gln Gly Gln Cys Val Lys Wing Gly Cys Asp Arg He He 675 680 685 gac tcc aaa aag aa ttt gat aaa tgt ggt gtt tgc ggg gga aat gga 2112 Aso Ser Lys Lys Lys Phe Asp Lys Cys Gly Val Cys Gly Gly Asn Gly 690 695 700 tet act tgt aaa aaa ata tea gga tea gtt act agt gca aaa ect gga 2160 Ser Thr Cys Lys Lys He Ser Gly Ser Val Thr Ser Wing Lys Pro Gly 705 710 715 720 tat cat gat ate ate here att cca act gga gec acc aa? ate gaa gtg 208 Tyr Has Asp He He Thr He Pro Thr Gly Wing Thr Asr! He Glu Val 725 730 735 aaa cag cgg aac cag agg gga tcc agg aac aat ggc ge ttt ctt gcc 2256 Lys Gln Arg Asn Gln Arg Gly Ser Arg Asn Asn Gly Ser Phe Leu Wing 7 0 745 750 ate aaa gct gct gat ggc here tat att attit ggt gac tac act ttg 2304 He Lys Wing Wing Asp Gly Thr Tyr He Leu Aan Gly Asp Tyr Tnr Leu 755 760 76E tcc acc tta gag ca gac att atg tac aaa ggt gtt gtc; ttg agg tac 2352 Ser Thr Leu Glu Gln Asp lie Met Tyr Lys Gly Val Val Leu Arg Tyr 770 775 780 a? c ggc tcc tet gcg gca ttg gaa aga att cgc age ttt age ect etc. 2400 Ser Gly Ser Ser Ala Ala Leu Glu Arg He Arg Ser Phe Ser Pro Leu 785 790 795 800 aaa gag ccc ttg acc ate cag gtc ctt act gtg ggc aat gcc ctt cga 2443 Lys Giu Pro Leu Thr He Gln Val Leu Thr Vai Gly? S? Wing Leu Arg 805 810 815 ect aaa att aaa tac acc tc ttac gta aag aag aag aa gaa tet ttc 2496 Pro Lys He Lys? Yr Thr Tyr Pho Val Lys Lys Lys Glu Ser Phe 820 825 S3C aat gct ate ccc act ttt tea gca tgg gtc att gaa gag tgg ggc gaa 2544 Asn Ala He Pro Thr Phe Ser Wing Trp Val He Giu Glu Trp Gly Gl 835 840 845 tgt c;: aag tea tgt gaa ttg ggt tgg cag aga aga ctg j- gaa tgc 2532 Cys Ser Lys Ser Cys Glu Leu Gly Trp Gln Arg Arg Leu Val Giu Cye E50 855 860 cga gac att aat gga cag ect gct tcc gag tgt gca aag gaa gtg aag 2640 Arg Asp He Asn Gly Gln Pro Wing Ser Glu Cys Wing Lys Glu Vai Lys 865 870 875 880 cca gcc age acc aga ect tgt gca gac cat ccc tgc ccc cag tg cag 268S Pro Wing Ser Thr Arg Pro Cys Wing Asp His Pro Cys Pro Cln Trp Gln 885 890 895 ctg sgg gag tgg tea tea tgt tet aet acc tgt ggg aag ggt tac aaa 2736 Leu Gly Glu Trp Ser Ser Cys Ser Lys Thr Cys Gly Lys Gly Tyr Lys 900 905 SIO aaa aga age ttg aag tgt ctg tcc cat gat gga ggg gtg ta tet cat 2784 Lys Arg Ser Leu Lys Cys Leu Ser Hi s ñsp Gly Gly Val e Ser Has 915 920 925 gag age tgt gat ect tta aag aaa ect aaa cat ttc ata falls ttt tgc 2832 Glu Ser Cys Asp Pro Leu Lya Lys Pro Lys His Phe He As Phe Cys 930 935 940 here at gca gaa tgc agt taa gtggtttaag tggtgttagc tt gaggcaa 2S83 Thr Met Ala Glu Cys Ser 945 950 ggcaaagtga ggaagggctg gtgcagggaa agcaagaagg ctggagggat ccagcgtatc 2943 ttgccagtaa ccagtgaggt ggtgggatta gtatcagtaa tagaaaagga tgggggtaga 3003 gttgaatcat cagagtaaac tgccagttgc aaatttgata ggatagtt = g tgaggattat 3063 taacctctga gcagtgatat agcataataa anccccgggc attattatta ttatttcttt 3123 tgttacatct attacaagtt tagaaaaaac aaagcaattg tcaaaaaaaa aaaaaaaaaa 3183 aaaaaaaaaa aaagggcggc cgctctagag gatccctcga ggggcccaag cttacgcgtg 3243 catcntgtca tnagtctn 3261 c2I0 > 2 < 211 > 950 < 212 > PRT < 2I3 > Homo sapiens < 4CC > 2 Met Gly Asn Wing Glü Arg Wing Pro Gly Ser Arg Being Fhe ly? Ro Val 1 5 10 15 Pro Thr Leu Leu Leu Leu Wing Wing Wing Leu Leu Wing Vai Ser? Sp Aia 20 25 30 Leu Gly Arg Pro Ser Glu Glu Asp Glu Glu Leu Val Val Pro Glu Leu 35 40 45 Glu Arg Wing Pro Gly His Gly Thr Thr Arg Leu Arg Leu His Wing Phe 50 55 60 Asp Glri Gln Leu Asp Leu Glu Leu Arg Pro Asp Ser Ser phe Leu Ala 65 70 75 80 Pro Gly Phe Thr Leu Gln Asn Val Gly Arg Lys Ser Gly Ser Glu Thr 85 90 95 Pro Leu Pro Giu Thr Asp Leu Wing Hys Cys Phe Tyr Ser Gly Thr Val 100 105 110? Sn Cly Asp Pro Ser Be Ala Ala Ala Leu Ser Leu Cys Slu Gly Val 115 120 12? Arg Gl ^ r Wing Phe Tyr Leu Leu Gly Glu Wing Tyr Phe Ilß Gln Pro Leu 130 135 140 Pro Al * Wing Ser Glu Arg Leu Wing Thr Wing Wing Pro Giy Glu Lys Pro 145 150 155 160 Pro lé Pro Leu Gln Phe His Leu Leu Arg Arg Asn Arg Gln Gly Asp 165 170 175 Val Gly Gly Thr Cys Gly Val Val Asp Asp Glu Pro Ar pro Thr Gly 180 185 190 Iys Ala Glu Thr Glu Asp Glu Asp Glu Gly Thr Glu Gly Glu Asp Gl u 195 200 2C? Giy Pro Gin Trp Ser Pro Gln Asp Pro Wing Leu Gln Gly Val Gly Gln 21o 215 220 Pro Thr Gly Thr Gly Ser He Arg Lys Lys Arg Phe Vai Se Ser 225 225 235 240 Arg Tyr Val Giu Thr Met Leu Val Wing Asp Gln Ser Me Wing Glu Phe 245 250 2S5 H ^ s Gly Ser Gly Leu Lys His Tyr Leu Leu Thr Leu Pr.s Ser Val Wing 260 265 270 Arg Leu Tyr Lys Hxs Pro Ser He Arg Asn Ser Val Ser Leu Val 275 280 IS z Val Val Lys He Leu Val He HIS Asp Glu Glp Lys Giy Pro Glu Val 290 295 300 Thr Ser Asn Ala Ala Leu Thr Leu ftrg Asn Phe Cys As Trp Glp Lys 305 310 315 320 Gln His Asn Pro Pro Ser Asp Arg Asp Ala Glu His Tyr Asp Th? Ala 325 330 335 He Leu Phe Thr Arg Gln Asp Leu Cys Gly Ser Gln Thr Cys Asp Thr 340 345 350 Leu Giy Met Wing Asp Val Gly Thr Val Cys Asp Pro Ser Arg Ser Cys 355 360 365 Ser Val He Glu Asp Asp Gly Leu Gln Wing Wing Phe Thr Thr Wing His 370 375 380 Giu Leu Gly His Val Phe Asn Met Pro Hís Asp Asp Ala Lys Gln Cys 385 390 395 400 Ala Ser Leu Asn Gly Val Asn Gln Asp Ser Met Met Met Ala Ser Met 405 410 415 Leu Ser Asn Leu Asp His Ser Gis Pro Trp Ser Pro Cys Ser Wing Tyr 420 425 430 Met He Thr Ser phe Leu Asp Asn Gly His Gly Glu Cys Leu Met Asp 435 440 445 Lys Pre Gln Asn Pro He Gln Leu Pro Gly Asp Leu P Gly The Ser 450 455 460 Tyr Asp Wing A = n Arg Gln Cys Gln Phe Thr Phe Gly Glu Asp Ser Lys 465 470 475 480 H s Cys Pro Asp Ala Ala Ser Thr Cys Ser Thr Leu Trp Cys Thr Gly 485 490 495 Thr Ser Gly Gly Val Leu Val Cys Gln Thr Lys His P e Pro Trp Wing 5C0 505 510 Asp Gly Thr Ser Cys Gly Glu Gly Lys Trp Cys He As.- Gly Lys Cys 515 520 5 S Val Asn Lys Thr Asp Arg Lys flis Phe Asp Thr Pro Fhe His Gly Ser 530 535 540 Trp Gly Met Tr? Gly Pro Trp Gly Asp Cys Ser Arg 7, -.r Cys Gly Gly 545 550 555 5É0 Giy Val Gln Tyr Thr Met Arg Glu Cys Asp Asn Pro Val Tro Z.ys Asn 565 570 575 Gly Gly Lys Tyr Cys Glu Gly Lys Arg Val Arg Tyr Arg Ser cys Asn 5S0 585 590 Leu Giu Asp Cys Pra Asp Asn Asn Gly Lys Thr Phe Arg Glu Glu Gln 595 600 605 Cys Glu Ala His Asn Glu Phe Ser Lys Wing Ser Phe Gly Ser Gly Pro 610 615 620 Wing Val Glu Trp He Pro Lys Tyr Wing Gly Val Ser Pro Lys Asp Arg 625 630 635 640 Cys Lys Leu He Cys Gln Wing Lys Giy He Gly Tyr Phe Phe. Val Leu 645 650 655 Gln Pro Lys Val Val Asp Gly Thr Pro Cys Ser Pro Asp Ser Thr Ser 660 665 670 Val Cys Val Gl Gly Gln Cys Val Lys Wing Gly Cys Asp Arg He He 675 680 685 Asp Ser Lys Lys Lys Phe Asp Lys Cys Gly Val Cys Gly Gly Asn Gly 690 695 700 Be Thr Cys Lys Lys Be Ser Giy Ser Val Thr Be Ala Lys Pro Gly 705 710 715 720 Tyr His Asp He He Thr He Pro Thr Gly Wing Thr Asn He Glu Val 725 730 735 Lys Glr. Arg Asn Gln Arg Gly Ser Arg Asn Asn Giy Ser Phe Leu Wing 740 45 750 lie Lys Wing Wing Asp Gly Thr Tyr He Leu Asn Gly Asp Tyz Thr Leu 755 760 7c5 Ser Thr Leu Glu Gln Asp He Met Tyr Lys Gly Val Vai Leu Arg Tyr 770 775 780 Ser Gly Ser Be Ala Aia Leu Glu Arg He Arg Ser Phe Ser Pro Leu 765 790 795 800 Lys C-lu Pro Leu Thr He Gln Val Leu Thr Val Gly Asr. Ala Leu Arg 805 810 S15 Pro Lys He Lys Tyr Thr Tyr Phe Val Lys Lys Lys Lys Glu Ser Phe 820 825 830 Asn Wing Pro Thr Phe Ser Wing Trp Val He Glu Glu Trp Gly Glu 835 840 845 Cys Ser Lys Ser Cys Glu Leu Gly Trp Gln Arg Arg Leu Val Glu Cys 850 855 860 Arg ñsp He Asn Gly Gln Pro Wing Ser Glu Cys Wing Lys Glu Val Lys 865 870 875 880 Pro Wing Being Thr Arg Pro Cys Wing Asp His Pro Cys Pro Gln Trp Gln 685 890 895 Leu Gly Glu Trp Ser Ser Cys Ser Lys Thr Cys Gly Lys Gly Tyr Lys 900 905 910 Lys Arg Ser Leu Lys Cys Leu Ser His Asp Gly Val Leu Ser Hi = 915 920 925 Glu Ser Cys Asp Pro Leu Lys Lys Pro Lys His Phe He Asp Phe Cys 930 935 940 Thr Met Wing Glu Cys Ser 945 950 < 210 > 3 < 211 > 3008 < : 212 > DNA < 213 > Homo sapiens 22C > < 221 > CD? < 22Z > íl) .. 2670) < 22 > 221 > IT IS NOT INSURANCE < 222 (2887) < 223 > It can be any nucleic acid < 22C > < 221 > IT IS NOT INSURANCE < 222 > (2957) < 2 3 > It can be any nucleic acid < 220 > < 221 > IT IS NOT SECURE 222 > (2970) < 223 > It can be any nucleic acid < 220 > < 221 > IT IS NOT INSURANCE < 222 > (2981). < 223 > It can be any nucleic acid < 400 > 3 atg ttc ccc gcc ccc gcc gcc ccc cgg tgg ctt ccg ttc ctg ctg ctg 48 Met Pne Pro Wing Pro Wing Wing Pro Arg Trp Leu Pro Phe Leu Leu Leu 1 5 10 15 ctg ctg ctg ctg ctg ctg ccg ctg gcc cgc ggc gcc ccg gcc cgg ccc 96 Leu Leu Leu Leu Leu Leu Pro Leu Ala Arg Gly Ala Pro Wing Arg Pro 20 25 • 30 gca gcc ggg ggg cag gcc tcg gag ctg gtg gtg ccc acg cgg ttg ccc 144 Wing Wing Gly Gln Gln Wing Wing Glu Leu Val Val Pro Thr Arg Leu Pro 35 40 45 ggc age gcg ggc gag etc gcg etc falls ctg tcc gcc ttc ggc aag ggc 192 Gly Ser Wing Gly Glu Leu Wing Leu His Leu Ser Wing Phe Gly Lys Gly 50 55"60 ttc gtg ttg cgc ctg gcg ccc gac gac age ttc ctg gcg ccc gag ttc 240 Phe Val Lßu Arg Leu Wing Pro Asp Asp Ser Phe Leu Wing Pro Glu Phe 65 70 75 80 aag ate gag cgc etc ggg ggc tcc ggc cgg gcg gsg ggc ggc gag cgg 288 Lys He Glu Arg Leu Gly Gly Ser Gly Arg Wing Thr Gly Gly Glu Arg 85 90 95 ggg ctg cgc ggc tgt ttt ttt tc ggc acc gtg aat ggg gag ccc gag 336 Gly Leu Arg Gly Cys Phe Phe Ser Gly Thr Val Asn Gly Glu Pro Glu 100 105 110 tcg ctg gcg gcg gtc age ctg tgc cgc ggg ctg age ggc ctg ctg ttc 384 Ser Leu Ala Ala Val Ser Leu Cys Arg Gly Leu Ser Gly Be Phe Leu 115 120 125 ctg gac ggc gag sag ttc acc ate cag ccg cag ggc gcg ggg ggc ccc 432 Leu Asp Gly Glu Glu Phe Thr He Gln Pro Gln Gly Ala Giy Gly Ser 130 135 140 ctg gct cag ccg falls cgc ctg cag cgc tgg ggt ccc gcc gga gcc cgc 480 Leu Ala Gln Pro His Arg Leu Gln Arg Trp Gly Pro Wing Gly Ft Arg 145 150 155 160 ccc etc ccg cga gga ccc gag tgg gag gtg gag acg gga gag ggt cag 528 Pro Leu Pro Arg Gly Pro Glu Trp Glu Val Glu Thr Gly Glu Gly Gln 165 170 175 agg cag gag aga gga gac drops cag gag gac age gag gag age ca 576 Arg Gln Glu Arg Gly Asp His Gln Glu Asp Ser Glu Glu Glu Ser Gln 180 185 190 gaa gag gag gca gag ggc gct age gag ccg cca ccg ccc cg gg gcc 624 Glu Glu Glu Glu Wing Gly Gly Wing Ser Glu Pro Pro Pro Pro Gw Wing 195 195 205 acg agg agg acc aag cgg ttt gtg tet gag gcg cgc ttc gt? gag acg 672 Thr Ser Arg Thr Lys Arg Phe Val Ser Glu Ala Arg P.- ~ Val Glu Thr 210 215 220 ctg ctg gtg gcc gat gcg tcc atg gct gcc ttc tac gcc gcc gac ctg 720 Leu Leu Val Ala Asp Ala Ser Met Ala Ala Phe Tyr Gl and Ala Asp Leu 225 230 235 240 cag aac falls t ctg atg tet gtg gca gcc gga cga ate tac aag 768 Gln Asn His He Leu Thr Leu Met Ser Val? La Ala Are rir Tyr Lys 245 250 255 falls ccc age ate aag aat tcc ate aac ctg atg gtg gts aaa gtg ctg 816 His Pro Ser He Lys Asn Ser He Asn Leu Met Val Val Lys Val Leu 260 265 270 ate gta gaa gat gaa aaa tgg ggc cca gag gtg tcc gac aat ggg ggg 864 He Val Glu Asp Glu Lys Trp Gly Pro Glu Val Ser Asp Asn Gly Gly 275 280 2e5 ctt ac "ctg cgt aac ttc tgc ase tgg cag cgg cgt ttc aac cag ccc 912 Leu Thr Leu? rg Asn Phe Cys Agn Trp Glp Arg Arg ¡? S AS? Gln Pro 290 295 300 age gaq cgc falls cca gag falls t? C gac acg gcc ate ctg etc acc aga 960 Ser Aso Arg His Pro Glu His Tyr Asp Thr Ala He Leu. Leu Thr Arg 305 310 315 320 cag aac ttc tgt ggg cag gag ggg ctg tgt gac acc etc ggt gtg gca 1008 Gln Asr,? He Cys Gly ln Glu Gly Leu Cys Asp Thr La- Gl and V? >; 1 Ala 325 330 335 gac ate ggg acc att tgt gac azc aac asa age tgc tcc gtg ate gag 105Ó Asp He Gly Thr He Cys Asp Pro Asn Lys Ser Cys Ser Val He Glu 340 345 350 gat gag ggg etc cag gcg gcc falls acc ctg gcc cat gaa cta ggg drops 1104 Asp Glu Gly Leu Gin Ala Wing His Thr Leu Ala Ris Gl- Leu Gly His 355 360 3 £ 5 gtc etc age atg ccc falls gac gac tcc aag ccc tgc ara cgs etc ttc 11E2 Val Leu Ser Met Pro His Asp Asp Ser Lys Pro Cys T-.r Arg Leu Phe 370 375 38C ggg ect atg ggc aag falls drops gtg atg gca ccg ctg ttc gtc falls ctg 1200 Gly Pro Met Giy Lys His His Vai Ket Ala Pro Leu Pr .e al His Leu 385 390 395 400 aac cag acg ctg ccc tgg ccc tcg age gcc atg tat etc here gag 1248 Asn GLn Thr Leu Pro Trp Ser Pro Cys Ser Wing Met Tyr Leu Thr Glu 405 410 415 ctt cg gac ggc ggg falls gga gac tgt etc ctg gat gcc ect ggt gcg 1296 Leu ~ c hsp Gly Gly His Gly Asp Cys Leu Leu Asp Wing Pro Gly Wing 420 425 430 gcc ctg ccc etc ccc here ggc etc ccg ggc cgc atg gcc ctg tac cag 1344 Wing The Pro Leu Pro Thr Gly Leu Pro Gl and Arg Met Ala Leu Tyr Gln 435 440 445 ctg falls cag tgc agg cag ate ttt ggg ccg gat ttc cgc falls tgc 1392 Leu Asp Gln Gln Cys Arg Gln He Phe Gly Pro Asp Phe Arg His Cys 450 455 460 ccc aac acc tet gct cag gac gtc tgc gcc cag ctt tgg tgc falls act 1440 Pro Asn Thr Ser Wing Glp Asp Val Cys Wing Glp Leu Trp Cys His Thr 465 470. 475 480 gat ggg gct gag cc cg tgc falls acg aag ggc age ctg ccc tgg 1488 Asp Gly Ala Glu 'Pro Leu Cys His Thr Lys Asn Gly Ser Leu Pro Trp 485 490 495 ect gac ggc acg ccg tgc ggg ect ggg drops etc tgc tea gaa ggc age 1536 Wing Asp Gly Thr Pro Cys Gly Pro Gly His Leu Cys Ser G¿ «Gly Ser -500 505 S10 tgt cta ect gag gag gag agg ccc aag ccc gtg gta gat gga 1584 Cys Leu Pro Glü Glu Glu Val Glu Arg Pro Lys Pro Val Val Asp Gly 515 520 525 ggc tgg gca ccg tgg gga ccc tgg gga gaa tqt tet cgg acc tgt gga 1632 Gly Trp Pro Wing Trp Gly Pro Trp Gly Glu Cys Ser Arg Th Cys Gly £ 30 535 540 gga ggs gca cag ttt tea falls cgt gag tgc aag gac ccc ga? ect cag 1680 Gly Giy Val Cln Phe Sar His Arg Glu Cys Lys Asp Pro Glu Pro Gln 545 550 555 560 aat gga gga aga tac tgc ctg ggt cgg aga gcc aag tac cag tea tgc 1728 Asr. 31and Gly Arg Tyr Cys Leu Gly ñrg Arg Wing Lys Tyr Ql Ser Cys 565 575 falls acg gag gag tgc ccc ect gac ggg aaa age ttc agq gag cag cag 1776 His Thr Glu Glu Cys Pro Pro Asp Gly Lys Ser Phß Arg Glu Gln Gin 580 585 590 tgt cag aag tat aat gcc tac aat tac act gac atg gat gg aat etc 1824 Cys Glu Lys Tyr Asn Wing Tyr Asn Tyr Thr Asp Met Asp Gly Asn Leu 595 600 605 ctg cag tgg gtc ccc aag tat gct ggg gtg tcc ccc csg gac cgc tgc 1872 Leu Gip Trp Val Pro Ly = Tyr Wing Gly Vai Ser Pro Are Asp Arg Cys 615 620 aag ttc ttc tgc cga gcc cgg ggg agg age gag ttc aaa gtg ttc gag 1920 Lys Leu Phe Cys Arg Wing Arg Gly Arg Ser Glu Phe Lys Val Phe Glu 625 630 635 640 gcc aag gtg att gat ggc acc cfcg tgt ggg cca gaa here. ctg gcc ate 1966 Ala Lys Val He Asp Gly Thr Leu Cys Gly Pro Glu Thr Leu Ala He 645 650 655 tgt gtc cgt ggc cag tgt gtc aag gcc ggc tgt gac cat gtg gtg gac 2016 Cys Val Arg Gly Gln Cys Val Lys Ala Gly Cys Asp His Val Val Asp 660 665 670 tcg ect cgg aag ctg gac aaa tgc ggg ggg ggc ggc aaa ggc aac 2064 Ser Pro Arg Lys Leu Asp Lys Cys Gly Val Cys Gly Giy Lys Gly Asn 675 680 685 tcc tgc agg aag gtc tcc ggg tcc etc acc ccc acc aat tat ggc tac 2112 Ser Cys Arg Lys Val Ser Gly Ser Leu Thr Pro Thr Asr. Tyr Gly Tyr 690 695 700 aat gac att gtc acc ate cca gct ggt gcc act aat att gac gtg aag 2160 Asn Asp He Val Thr He Pro Wing Gly Wing Thr Asn Ha Asp Val Lys 705 710 715 Q cag cgg age falls ccg ggt gtg cag aac gat ggg aac tac ctg gcg cgc 2208 Cln Arg Ser Hís Pro Gly Val Gln Asn Asp Gly Asn Tyr Leu Ala Leu 725 730 735 aag acg gct gat ggg cag tac ctg etc aac ggc aac etc gcc ate tet 2256 Lys Thr Wing Asp Gly Gln Tyr Leu Leu Asn Gly Asn Leu Wing Be 740 745 750 gcc ata gag cag gac ate ttg gtg aag ggg acc ate etc aag tac age 2304 Wing He Glu Gln A = p ile Leu Val Lys Gly Thr He Lßu Lys Tyr Ser 755 760 765 gsc tcc ate gcc acc ct? gag cgc ctg cag age ttc cgc ccc ttg cca 2352 Gly Ser He Wing Thr Leu Glu Arg Leu Gln Ser Phe Arg Pro Leu Pro 770 775 780 gag ect ct? here gtg cag etc ctg here gtc ect ggc gac gtc ttc ccc 2400 Giu Pro Leu Thr Val Gln Leu Leu Thr Val Pro Gly Glu Val Phe Pro 785 790 795 800 cea aaa gtc aaa tac acc ttc ttt gtt ect aat gac gtc gac ttt age 2448 Pro Lys Val Lys Tyr Thr Phe Fhe Val Pro As Asp Val Asp Phe Ser 805 810 S15 atg cag age age aaa gag aga gca acc acc aac ate ate cgg ctg 2496 Met Gin Ser Ser Lys Glu Arg Ala Thr Thr Asn He lis Gln Pro Leu 820 825 830 etc falls gca cag tgg gtg ctg ggg gac tgg tet gag tgc tet age acc 2544 Leu HIS Wing Gln Trp Val Leu Gly Asp Tep Ser Glu Cys -Ser Ser Thr 835 840 845 tgc ggg gcc ggc tgg cag agg cga act gta gag tgc agg gac ccc tcc 2592 Cys Gly Wing Gly Trp Gln Arg Arg Thr Val Glu Cys Arg Asp Pro Ser 850 855 860 ggc cag gcc tet gcc acc tgc aac aag gct ctg aaa ccc gag gat gcc 2640 Gly Gln Ala Ser Wing Thr Cys Asn Lys Wing Leu Lys Pro Glu Asp Wing 865 870 875 880 aag ccc tgc gaa age cag ctg tgc ccc ctg tgattcaggg gggcaggggc 2690 Lys Pro Cys Glu Ser Gln Leu Cys Pro Leu 885 890 cagtcttgtg ctcctggaca tgcggtactg aggtgcagac aaggtctcca ctgtggtgac 2750 tgggtccctt ggecatatca aggcagcacg gcccacccag gcctcccatt gccgcaaccc 2H10 ctccagtact gcacaaattc ctaaggggga agagaaaagg tatggggcgg caaaacctat 2870 catcaacrgt ccawtgnaat ggaacttgct cgggttcaat taaaggcata agttaaagta 2930 gatcaacaga aattcattat cctcacntca tctgttgcan aaaaaaaaaa aaaaaaaa 2990 ntaaaaaaaa gatacaacta 3008 < 210 > 4 < 211 > 890 < 212 > PRT < twenty-one? > Homo sapiens < 400 > 4 Kec Phe Pro Wing Pro Wing Wing Pro Arg Trp Leu Pro Phe Leu Leu Leu 1 10 15 Leu Leu Leu Leu Leu Pro Leu Wing Arg Gly Wing Pro Wing Arg Pro 20 25 30 Wing Wing Gly Glly Wing Ala Ser Glu Leu Vai Val Pro Thr Arg Leu Pro 35 40 45 Gly Be Ala Gly Glu Leu Ala Leu His Leu Be Ala Phe Gly Lys Gly 50 55 60 Phe Val Leu Arg Leu Ala Pro Asp Asp Ser Phe Leu Ala Pro Glu Phe 65 70 75 80 Lys He Glu Arg Leu Gly Gly Ser Giy Arg Wing Thr Gly Giy GJu Arg 85 90 95 Gly Leu Arg Gly Cys Phe Phe S «r Gly Thr Val Asn Gly Glu Pro Glu 100 '105 ilC Ser Leu Ala Ala Val Ser Leu Cys Arg Gly Leu Ser Gly Ser Phe Leu 115 120 125 Leu Asp Gly Glu Giu Phe Thr lie Gln Pro Gln Gly Wing Gly Gly Ser 130 135 140 Leu Ala Gln Pro His Arg Leu Gln Arg Trp Gly Pro Ala Gly Ala Arg 145 150 155 160 Pro Leu Pro Arg Gly Pro Glu Trp Glu Val Gl? Thr Gly Glu Gly Gln 165 170 175 Arg Gln Glu Arg Gly Asp His Gln Glu Asp Ser Glu Glu Glu Ser Gin 180 185 190 Glu Giu Glu Wing Glu Gly Wing Ser Glu Pro Pro Pro Pro Leu Giy Wing 195 200 2QS Thr Ser Arg Thr Lys Arg Phe Val Ser Glu Wing Arg Phe Val Glu Thr 210 215 220 Leu Leu Val Wing Asp Wing Ser Met Wing Wing Phe Tyr Gly Wing Asp Leu 225 230 235 240 Gln Asn His He Leu Thr Leu Met Ser Val Ala Wing Arg He Tyr Lys 245 250 255 His Pro Ser He Lys A = n Ser He Asn Leu Het Val Val Lys Vai Leu 260 265 270 He Vai Glu Asp Glu Lys Trp Gly Pro Glu Val Ser Asp Asn Gly Gly 275 280 265 Leu Thr Leu Arg Asri Phe Cys Asn Trp Gln Arg Arg Phe Asn Gln Pro 290 295 300 Ser Asp Arg His Pro Glu His Tyr Asp Thr Ala He Leu Leu Thr Arg 305 310 335 320 Gln? Sn Phe Cys Giy Gln Glu Gly Leu Cys Asp Thr Leu < 31 and Val Ala 325 330 335 Asp He Gly Thr He Cys Asp Pro Asn Lys Ser Cys Ser Val He Glu 340 345"350 Asp Glu Giy Leu dn Ala Ala K? S Thr Leu Ala His Glu Leu Gly Hii 355 360 365 Val Leu Ser Met Pro His Asp Asp Ser Lys Pro Cys Thr Arg Leu Phe 370 375 380 Gly Pro Met Gly Lys His His Val Val Met Wing Pro Leu Phe Val His Leu 335 390 395 400 Asr. Gln Thr Leu Pro Trp Ser Pro Cys Ser Wing Met Tyr Leu Thr Glu 405 410 415 Leu Leu Asp Giy Gly His Gly Asp Cys Leu Leu Asp Wing Pro Gly Wing 420 425 430 Wing Leu Pro Leu Pro Thr Gly Leu Pro Gly Arg Met Wing Leu Tyr Gln 435 440 445 Leu Asp Gln Gln Cys Arg Gln He Phe Gly Pro Asp Phe Arg His Cys 4S0 455 460 Pro Asn Thr Ser Ala Gln Asp Val Cys Ala Gln Leu Trp Cys His Thr 465 470 475 480 Asp Gly Ala Glu Pro Leu Cys His Thr Lys Asn Gly Ser Leu Pro Trp 485 490 495 Wing Asp Gly Thr Pro Cys Gly Pro Gly His Leu Cys Ser Glu Gly Ser 500 505 510 Cys Leu Pro Glu Glu Glu Val Glu Arg Pro Lys Pro Val Val Asp Gly 515 520 525 Gly Trp Pro Wing Trp Gly Pro Trp Gly Glu Cys Ser Arg Thr Cys Gly 530 535 540 Gly Gly Val Gln Phe Ser His Arg Glu Cys Lys Asp Pro Glu Pro Gln 545 550 555 560 Asn Gly Gly Arg Tyr Cys Leu Giy Arg Arg Wing Lys Tyr Gln Ser Cys 56S 570 575 H s Thr Glu Glu Cys Pro Pro Asp Gly Lys Ser Phe Arg Glu Gln Gln 580 585 590 Cys Giu Ly = Tyr Asn Ala Tyr Asn Tyr Thr Asp Met Asp Gly Asn Leu 595 600 605 Leu Gln Trp Val Pro Lys Tyr Ala Giy Val Ser Pro Arg Asp Arg Cys 610 615 620 Lys Leu Phe Cys Arg Wing Arg Gly Arg Ser Glu Phe Lys Val Phe Glu 625 630 635 640 Wing Ly = val He Asp Gly Thr Leu Cys Gly Pro Glu Thr Leu Ala He 645 645 655 Cys'. "To Arg Gly Gln Cys Val Lys Wing Gly Cys Asp Kis Val Val Asp 650. 665 670 Ser Pro Arg Lys Leu Asp Lys Cys Gly Val Cys Gly Gly Lys Gly Asn 675 6B0 685 Ser Cys Arg Lys Val Ser Gly Ser Leu Thr Pro Thr Asn Tyr Gly Tyr 690 695 700 Asn Asp He Val Thr He Pro Wing Gly Wing Thr Asn He Asp Val Lys 705 710 715 720 Gln Arg Ser His Pro Gly Val Gln Asn Asp Gly Asn Tyr Leu Ala Leu 725 730 735 Lys Thr Wing Asp Gly Gln Tyr Leu Leu Asn Gly Asn Leu Wing Be 740 745 750 Wing He Glu Gln Asp He Leu Val Lys Gly Thr He Leu Lys Tyr Ser 755 760 65 Gly Ser He Wing Thr Leu Glu Arg Leu Gln Ser Phe Arg Pro Leu Pro 770 775 780 Glu Pro Leu Thr Val Gin Leu Leu Thr Val Pro Gly Glu Val Phe Pro 785 790 795 800 Pro Lys Val Lys Tyr Thr Phe Phe Val Pro As Asp Val Asp Phe Ser 805 810 815 Met Gln Ser Ser Lys Glu Arg Wing Thr Thr Asn He He Gin Pro Leu 820 825 830 Leu Hrs Wing Gln Trp Val Leu Gly Asp Trp Ser Glu Cys Ser Ser Thr 835 840 845 Cys Gly Wing Gly Trp Gln Arg Arg Thr Val Glu Cys Are Asp Pro Ser 850 855 860 Gly Glc Wing Being Wing Thr Cys Asn Lys Wing Leu Lys Prc Giu Asp Wing 865 870 875 880 Lys Pro Cys Glu Ser Gln Leu Cys Pro Leu 885 890 < 210 > 5: 2II 1203 < 212 > PRT < 213 > Bovine < 400 > 5 Met Asp Pro Pro Ala Gly Ala Ala Gly Arg Leu Leu Cys Pro Ala Leu 1 5 10 15 Leu Leu Leu Leu Leu Leu Pro Leu Pro Ala Asp Ala Arg Leu Ala Ala 20 25 30 Ala Ala Ala Asp Pro Pro Gly Gly Pro Gln Gly His Gly Ala Glu Arg 35 40 45 He Leu Ala Val Pro Val Arg Thr Asp Ala Gln Gly Arg Leu Val Ser 50 55 60 His Val Val Ser Ala Ala Thr Ala Pro Ala Gly Val Arg Thr Arg Arg 65 70 '75 80 Ala Ala Pro Ala Gln He Pro Gly Leu Ser Gly Gly Ser Glu Glu Asp "85 90 95 Pro Gl and Gly Arg Leu Phe Tyr Asp Val Thr Val Phe Gly Arg Asp Leu 100 105 110 His Leu Arg Leu Arg Pro Asn Ala Arg Leu Val Ala Pro Gly Ala Thr 115 120 125 Val Giu Trp Gln Gly Glu Ser Gly Ala Thr Arg Val Glu Pro Leu Leu 130 135 140 Gly Thr Cys Leu Tyr Val Gly Asp Val Wing Gly Leu Wing Giu Ser Ser 145 150 155 160 Ser Vai Ala Leu Ser Asn Cys Asp Giy Leu Ala Gly Leu He Arq Met 165 170 175 Glu Glu Glu Glu Phe Phe He Glu Pro Leu Glu Lys Gly Leu Ala Wing 180 185 1S0 Lys Glu Wing Glu Gln Gly Arg Val Hxs Val Val Tyr HIS Arg Pro Thr 195 200 205 Thr Ser Arg Pro Pro Pro Leu Gly Gln Ala Leu Asp Thr Gly He Ser 210 215 220 Aid Asp Ser Leu Asp Ser Leu Ser Arg Ala Leu Cly Vai Leu Glu Glu 225 230 235 240 Arg Val Asn Ser Ser Arg Arg Arg Met Arg Arg His Ala Wing Asp Asp 245 250 255 Asp Tyr Asn He Glu Val Leu Leu Gly Val Asp Asp Ser Val Val Gln 260 265 270 Phe His Gly Thr Glu Kis Val Gln Lys Tyr Leu Leu Thr Lau Met As- 275 280 285 He Val Asn Glu He Tyr His Asp Glu Ser Leu Gly Al = His lie Asn 290 295 300 Val Val Leu Val Arg He He Leu Leu Ser Tyr Gly Lys Ser Met Ser 305 310 315 320 Leu He Glu He Gly Asn Pro Ser Gln Ser Leu Glu Asn Val Cys Arg 325 330 335 Trp Wing Tyr Leu Gln Gln Lys Pro Asp Thr Asp His Asp Glu Tyr His 40 345 350 Asp His Wing He Phe Leu Thr Arg Gln Asp Phe Gly Pro Ser Gly Met 355 36o 365 Gln Gly Tyr Ala Pro Val Thr Gi Ly MMeett CCyvss HHiiss PPrroo Val Arg Ser Cys 373 375 380 Thr Leu Asn His Glu Asp Gly Phe Ser Ser Ala Phe Val Val Ala His 385 390 395 400 Glu Thr Gly His Val Leu Gly Met Glu His Asp Gly Gln Gly Asn Arg 405 410 415 Cys Giy Asp Glu Val Arg Leu Gly Ser He Met Ala Pro Leu Val Gln 420 425 430 Wing Wing Phe His Arg Phe HIS Trp Ser Arg Cys Ser Glr. Without Giu Leu 435 44? 445 Ser Arg Tyr Leu His Ser Tyr ASE > Cys Leu Arg A3p Asp Pro Phe Thr '= 0 455 450 His Asp Trp Pro Wing Leu Pro Gln Leu Pro Gly Leu His Tyr Ser M ° t 465 470 475 430 Asn Glu Gln Cys Arg Phe Asp Phe Gly Leu Gly Tyr Met Met Cys Thr 485 490 495 Wing Pha Arg Thr Phe Asp Pro Cys Lys Gln Leu Trp Cys Ser His Pro 500 505 510 Asp Asn Pro Tyr Phe Cys Lys Thi-Lys Lys Gly Pro Prc Leu Asp Gly 515 520 Thr Met Cys Wing Pro Gly Lys His Cys Phe Lys Gly His Cys He Trc 530 535 54C Leu Tr.r Pro Asp He Leu Lys Arg Asp Gly Asn Trp Gly Wing Trp Ser 545 550 555 560 Pro Pne Gly Ser Cys Ser Arg Thr Cys Gly Thr Gly Val Lys Phe Arg 565 570 575 Thr Arg Gln Cys Asp Asn Pro His Pro Wing Asn Gly Gly Arg Thr Cys 580 585 590 Ser Giy Leu Wing Tyr Asp Phe Gln Leu Cys Asn Ser Gln Asp Cys Pro 595 600 605 Asp Ala Leu Ala A = p Phe Arg Glu Glu Gln Cye Arg Gln Trp Asp Leu 610 615 620 Tyr Phe Glu His Gly Asp Ala Gln His His Trp Leu Pro His Glu His 625 630 635. 640 Arg Asp Ala Lys Glu Arg Cys His Leu Tyr Cys Glu Ser Lys Glu Thr 645 650 655 Gly Glu Val Val Met Met Lys Arg Met Val His Asp Gly Thr Arg Cys 660 665 670 Ser Tyr Lys Asp Wing Phe Ser Leu Cys Val Arg Gly Asp Cys Arg Lys 675 680 685 Val Gly Cys Asp Gly Val He Gly Ser Ser Lys Gl Glu Asp Lys Cys 690 695 700 Gly Val Cys Gly Gly ñsp Asn Ser His Cys Lys Val Val Lys Gly Thr 705 710 715 720 Phe Ser Arg Ser Pro Lys Lys Leu Gly Tyr 'De Lys Ket Phe Glu lie 725 730 735 P or Wing Gly Wing Arg His Leu Leu He Gln Glu Wing Asp Thr Thr Ser 740 745 750 His His Leu Wing Vai Lys ftsn Leu Glu Thr Gly Lys Phe He Leu Asn 755 760 763 Glu Gl As Asp Val Asp Pro Asn Ser Lys Thr Phe lie Wing Met Gly 770 775 780 Val C-lu Trp Glu Tyr Arg Asp Glu ñsp Gly Arg Glu Chr Leu Gln Thr 7S? 790 795 800 Met Gly Pro Leu HIS Gly Thr He Thr Val Leu Val He Pro Glu Gly 805 810 815 Asp Ala Arg lie Ser Leu Thr Tyr Lys Tyr Met He H_s Glu Asp Ser 820 825 830 Leu Asn Val Asp Asp? Sn Asn Val Leu Glu Asp Asp Ser Val Giy Tyr 835 840 645 Glu Trp Wing Leu Lys Lys Trp Ser Pro Cys Ser Lys Pro Cys Gly Gly 850 855 860 Giy Ser Gln Phe Thr Lys Tyr Gly Cys Arg Arg Arg Leu Asp His Lys 865 870 875 880 Met Val His Arg Gly Phe Cys Aap Ser Val Ser Lys Pro Lys Ala lie 885 890 895 Arg Arg Thr Cys Asn Pro Gln Glu Cys Ser Gln Pro Val Trp Val Thr 900 905 910 Gly Glu Trp Glu Pro Cys Ser Arg Ser Cys Gly Arg Thr Gly Met Gln 915 920 925 Val Arg Ser Val Arg Cys Val Gln Pro Leu His Asn A = n Thr Thr Arg 930 935 940 Ser Val His Thr Lys His Cys Asn Asp Ala Arg Pro Glu Gly Arg Arg 945 950 955 960 Ala Cys A = n Arg Glu Leu Cys Pro Gly Arg Trp Arg Ala Gly Ser Trp 965 970 975 Ser Gln Cys Ser Val Thr Cys Gly A = n Gly Thr Glp Glu Arg Pro Val 980 985 99C Leu Cys Arg Thr Wing Asp Asp Ser Phe Gly Val Cys Arg Glu Glu Arlu 995 1000 1005 pro Glu Thr Wing Arg He Cys Arg Leu Gly Pro Cys Pro Arg Asn Thr ICIO 1015 1020 Ser Asp Pro Ser Lys Lys Ser Tyr Val Val Gln Trp Leu Ser Arg Pro 1025 1030 1035 1040 Asp Pro Asn Ser Pro Val Gln Glu Thr Ser Ser Lys Gly Arg Cys Gln 1045 1050 1055 Gly Asp Lys Ser Val Phe Cys Arg Met Glu Val Leu Ser Arg Tyr Cys 1060 1065 1070 Ser lie Pro Gly Tyr Asn Lys Leu Cys Cys Lys Ser Cys Asn Pro His 1075 1080 1085 Asp Asr. Leu Thr Asp Vai Asp Asp Arg Ala Glu Pro Pre Ser Gly Lys' .090 1095 1100 His Asr. Asp He Glu Glu Leu Met Pro Thr Leu Ser Val c Thr Leu 1105 1110 1115 1120 Val Met Glu Val Gln Pro Pro Pro Gly He Pro Leu Glu Val Frc Leu 1125 1130 1135 Asn Thr Ser Ser Thr Asn Wing Thr Glu Asp His Pro Glu Thr Asn Wing 1140 1145 1150 Val Asp Val Pro Tyr Lys He Pro Gly Leu Glu Asp Glu Val Gln Pro 1155 1160 1165 Pro Asn Leu He Pro Arg Arg Pro Ser Pro Tyr Glu Lys Thr Arg Asn 1170 1175 1180 Gln Arg He Gln Glu Leu He Asp Glu Met Arg Lys Lys Glu Met Leu 1185 1190 1195 1200 Gly Z. s Phe < 210 > 6 < 211 > 50 < 212 > PRT < 213 > Ho or sapiens < 400 > 6 Asp Asp Gly Trp Ser Pro Trp Ser Glu Trp Thr Ser Cys Ser Thr Ser 1 5 10 15 Cys Gly Asn Gly He Gln Gln Arg Gly Arg Ser Cys A = p Ser Leu Asn 20 25 30 Asn Arg Cys Glu Gly Be Ser Vai Glr. Thr Arg Thr Cys His He Gln 35 4C 45 Glu Cys 50 < 210 > 7 < 211 > 57 < 212 > PRT < 213 > Homo sapiens < 400 > 7 Asp Gly Gly Trp Ser His Trp Ser Pro Trp Ser Se? Cys Ser Val Thi 1 5 10 15 Cys Gly Asp Gly Val He Thr Arg He Arg Leu Cys Asn Ser Pro Ser 20 25 30 Prc GI? Met Asn Gly Lye Pro Cys Glu Gly Glu Wing Are Giu Thr Lys 35 40 45 Wing Cys Lys Lys Asp Wing Cys Pro He 50 55 < 210 > 8 < 211 > 57 < 212 > PRT < 213 > Homo sapiens < 400 > 8 Asn Gly Gly Trp Gly Pro Trp Ser Pro Trp Asp He Cys Ser Val Thr 1 5 10 15 Cys Gly Gly Gly Val Gln Lys Arg Ser Arg Leu Cys Asn Asn Pro Thr 20 25 30 Pro Gln Phe Gly Gly Lys Asp Cys Val Gly Asp Val Thr Glü Asn Gin 35 40 45 He Cys Asn Lys Gln Asp Cys Pro He 50 55 < 210 > 9 < 211 > 50 < 212 > PF.T < 213 > Homo sapiens < 40C > 9 Glu Glu Gly Trp Ser Pro Trp Wing Glu Trp Thr Gln Cys Ser Val Thr 1 10 ih Cy = Gly Ser Gly Thr Gln Gin Arg Gly Arg Ser Cys Asp Val Thr Ser 20 25 30 Asn Thr Cys Leu Gly Pro Ser He Gln Thr Arg Ala Cys Ser Leu Ser 35 40 45 Lys Cys 50 < 210 > ID < 211 > 57 < 212 > PRT < 213 > Homo sapiens < 400 > 10 Asp Gly Gly Trp Ser His Trp Ser Pro Trp Ser Ser Cys Ser Val Thr 1 5 10 15 Cys Gly Val Gly Asn He Thr Arg He Arg Leu Cys Asn Ser Pro Val 20 25 30 Pro Gin Met Gly Gly Lys Asn Cys Lys Gly Ser Gly Arg Glu Thr Lys 35 40 45 Wing Cys Glr. Gly Ala Pro Cys Pro He 50 55 < 210 > 11 < 211 > 56 < 212 > PRT < 213 > Homo sapiens < 400 > 11 Asp Gly Arg Trp Ser Pro Trp Ser Pro Trp Be Wing Cys Thr Val Thr 1 5 10 15 Cys Wing Gly Gly He Arg Glu Arg Thr Arg Val Cys Asn Ser Pro Glu 20 25 30 Pro Gln Tyr Gly Gly Lys Wing Cys Val Gly Asp Val Gln Glu Arg Gln 35 40 45 Met Cys Asn Lys Arg Ser Cys Pro 5C 55 < 210 > 12 < 211 > 3974 < 21 > DNA < 213 > Homo sapiens < 400 > 12 ggtacctaag tgagtagggc gtccgatcga cggacgcctt ttttttgaat tcgtaatcat 60 ggtcatagct gt ttcctgtg tgaaattgtt atccgctcac aattccacac aacatacgag 120 ccggaagcat aaagtgtaaa gcctggggtg cctaatgagt gagctaactc acattaattg 180 cgttgcgctc actgcccgct ttccagtcgg gaaaccrtgtc gtgceagctg cattaatgaa 240 t cggccaacg cgcggggaga ggcggtttgc gtattgggcg ctcttccgct tcctcgctca 300 ctgactcgct gcgctcggtc gt tcggctgc ggcgagcggt atcagctcac tcaaaggcgg 360 atccacagaa taatacggtt tcaggggata acgcaggaaa gaacatgtga gcaaaaggcc 420 agcaaaaggc caggaaccgt aaaaaggccg cgttgctggc gtttttccar aggctccgcc 480 gcatcacaaa cccctgacga aatcgacgct caagtcagag gtggcgaaac ccgacaggac 540 tataaagata ccaggcgttt ccccctggaa gctccctcgt gcgctctcct gttccgaccc 600 tgccgcttac cggatacctg tccgcctttc tcccttcggg aagcgtggcg ctttctcata 660 gctcacgctg taggtatctc agttcggtgt aggtcgttcg ctccaagctg ggctgtgtgc 720 acgaaccccc cgttcagccc gaccgctgcg ccttatccgg taactatcgt cttgagtcca 780 acccggtaag acacgactta tcgecactgg cagcagccac tggtaacagg attagcagag 840 cgaggtatgt ag gcggtgct acagagttct tgaagtggtg gcctaactac ggctacacta 900 gaagaacagt atttggtatc tgcgctctgc tgaagccagt taccttcgga aaaagagttg 960 gtagctcttg atccggcaaa caaaccaccg ctggtagcgg tggttttttt gtttgcaagc 1020 agcagattac gcgcagaaaa aaaggatctc aagaagatcc tttgatcttt tctacggggt 1080 gtggaacgaa ctgacgctca aactcacgtt aagggatttt ttatcgtcga ggtcatgaga 1140 gcgaaggcga caattcgcgc agcggcatgc atttacgttg atggtgcaaa acaccatcga 1200 acctttcgcg gtatggcatg atagcgcccg gaagagagtc aattcagggt ggtgaatgtg 1260 cgttatacga aaaccagtaa tgtcgcagag tatgccggtg tctcttatca gaccgtttcc 1320 cgcgtggtga accaggccag ccacgtttct gcgaaaacgc gggaaaaagt ggaascggcg 1380 atggcggagc tgaattacat tcccaaccgc gtggcacaac aactggcggg caaacagtcg 1440 ttgctgattg gcgttgccac ctccagtctg gccctgcacg cgccgtcgca aattgtcgcg 1500 gcgattaaat ctcgcgccga tcaactgggt gccagcgtgg tggtgtcgat ggtagaacga 1560 agcggcgtcg aagcctgtaa agcggcggtg cacaatcttc tcgcgcaacg cgtcagtggg 1620 ctgatcatta actatccgct ggatgaccag gatgccattg ctgtggaagc tgcctgcact 1680 AATGt GGCC cgttatttct tgatgtctct gaccagacac ccatcaacag tattattttc 1740 tcccatgaag acggtacgcg actgggcgtg gagcatctgg tcgcattggg tcaccagcaa 1800 atcgcgctgt tagcgggccc attaagttct gtctcggcgc gtctgcgtct ggctggctgg 1860 cataaatatc tcactcgcaa tcaaattcag ccgatagcgg aacgggaagg cgactggagt 1920 gttttcaaca gccatgtccg aaceatgcaa atgetgaatg agggcatcct tcccactgcg 1980 atgctggttg ccaacgatca gatggcgctg ggcgcaatgc gcgccattac cgagtccggg 2040 etgcgegttg gtgcggatat ctcggtagtg ggatacgacg ataccgaags cagctcatgt 2100 tatatcccgc cgttaaccac CATCA aacag gattttcgcc tgctggggca aaccagcgtg 2160 gaccgcttgc tgcaactctc tcagggccag gcggtgaagg gcaatcagct gttgcccgtc 2220 tcactggtga aaagaaaaac caccctggcg cccaatacgc aaaccgcctc tccccgcgcg 2280 ttggccgatt gctggcacga cattaatgca gastggaaag caggtttccc cgggcagtga 2340 attaatgtaa gcgcaacgca gttagcgcga attgtcgacc aaagcggcca tcgtgcctcc 2400 ccactcctgc agttcggggg catggatgcg cggatagccg ctgctggttt cctggatgcc 2460 gacggatttg cactgccggt agaactccgc gaggtcgtcc agcctcaggc agcagctgaa 2520 ccaactcgcg aggggatcga gcccggggtg ggcgaagaac tccagcatsa gatccccgcg 2580 ctggaggatc atccagccgg cgtcccggaa aacgattccg aagcccaace tttcatagaa 2640 ggcggcggtg gaatcgaaat ctcgtgatgg caggttgggc gtcgcttggt cggtcatttc 2700 gtcccgctca gaaccccaga gaagaactcg tcaagaaggc gatagaaggc gatgcgctgc 2760 gaatcgggag cggcgatacc gtaaagcacg aggaagcggt cagcccattc gccgccaagc 2820 tct cagcaa tatcacgggt agccaacgct atgtcctgat agcggtccgc cacacccagc 2880 cggceaeagt cgatgaatcc agaaaagcgg ccattttcca ccatgatatt cggcaagcag 2940 gcatcgccat gggtcacgac gagatcetcg ccgtegggca tgsgcgcctt gagcctggcg 3000 aacagttcgg ctggcgcgag cccctgatcc tcttcgtcca atcatcctg atcgacaaga 3060 ccggcttcca tccgagtacg tgctegctcg atgcgatgtt tcgcttqstg gtcgaatggg 3120 c ggtagccg gatcaagcgt atgcagccgc cgcattgcat cagccat at ggatactttc 3180 caaggtqaga tcggcaggag tgacaggaga tcctgccccg gc3Cttcgcc caatagcagc 3240 cagtcccttc ccgcttcagt gacaacgtcg agcacagctg cgcaaggaac gcccgtsqtg 3300 gccagccacg atagccgcgc tgcctcgtcc tgcagttcat tcagggcacc ggacaggtcg 3360 gtcttgacaa aaagaaccgg gcgcccctgc gctgacagcc ggaacacggc ggcatcagag 3420 cagccgattg tctgttgtgc ccagtcatag ccgaatagcc tctccaccca agcggccgga 3480 gaaeccgegt gcaatccatc ttgttcaatc atgcgaaacg atcctc = aka tgtctcttga 3540 tcagatcttg atcccctgcgr ccatcagatc cttggcggca agaaagccat ccagtttact 3600 ttgcagggct tcccaacctt accagagggc gccccagctg gcaattccgg ttcgcttgc. 3660 gtccataaaa ccgcccagtc tagctatcgc cat-gtaagcc cactgcaagc tacctgcttt 3720 ctctttgcgc ttgcgttttc ccttgtccag atagcccagt agctgacatt catccggggt 3780 cagcaccgtt tctgcggact ggctttctac gtgttccgct tcctttagca gcccttgcgc 3840 cctgagtgct tgcggcagcg tgaagcttaa aaaactgcaa aaaatagttt gacttgtgag 3900 ttaagatgta cggataacaa cccaattgtg agcggataac AATTT-acac attaaagagg agaaattaca TATG 3960 3974 < 210 > 13 < 211 > 112 < 212 > DNA < 213 > Homo sapiens < 400 > 13 aagcttaaaa aactgcaaaa aatagtttga cttgtgagcg gataacaatt aagatgtacc 60 caattgtgag cgqataacaa tttcacacat taaagaggag aaattacata tg 112 < 210 > 14 < 2H > 542 < 212 > DNA < 213 > Mus musculus < 220 > < 221 > IT IS NOT INSURANCE < 222 > (3) < 223 > It can be any nucleic acid < 220 > < 221 > IT IS NOT INSURANCE < 222 > (21) < 223 It can be any nucleic acid < 220 > < 22i > IT IS NOT INSURANCE < 222 > (22) < 223 > It can be any nucleic acid < 22C > < 221 > IT IS NOT INSURANCE < 222 > (3613 <223> Can be any nucleic acid <220> <221> IS NOT SECURE '"<222 ^ (369) <223> Can be any nucleic acid < 22C > < < 223 < 223 >; 221 > IT IS NOT SECURE < 222 > Í407) < 223 > It can be any nucleic acid < 220 > < 221 > IT IS NOT SECURE < 222 > (427) < 223 > It can be any nucleic acid <220> <221> NOT SECURE <222> (479) <223> Can be any nucleic acid <220> <221> IS NOT SECURE < 222 > í 482) < 223 > It can be any nucleic acid < 220 > < 221 > is NOT SECURE < 222 > {. 535) < 223 > It can be any nucleic acid < 400 > 14 gtncgaattt cggcaegaga nnttagacge cttttcatgg aagctggcga atgtgggggc 60 cttggggaga c gttcgaga acgtgcggtg gaggagtcca gtacacgacg agggaatgtg 120 acaacccagt eccaaagaat ggagggaagt actg tgaagg caaacgagtg cgctacagat 180 cctgtaacct tgaggactgt ccagacaata atggaaaaac ctttagagsg gaacaatgtg 240 cgagttttca aagcacacaa aaagcttcct ttgggagtgg gcctgcgg g gaatggattc 300 ccaactacgc tggcgtctca ccaaaggaca ggtgcaagtt catgttgc? to agccaaaggc 360 nctggctant tctttcgttt tgcagcccaa ggttgttagg tgggtant c atgttaggcc 420 cagattncac ctttgtctgt gtgcaaggac agtgtgttaa aagttggttg tgatccgcnt 480 cntagattcc aaaaggagtt ttgttaatgt ggtgttttcn gggggaatag tctantttta 540 542 < 21C > 15 c211 > 320 < 212 > DNA < 213 > Unknown < 22C > < 223 > Description of the Unknown Body: Unknown < 400 > 15 cagagaacat tcgccccact cttcaatgac ccatgctgaa aaagtgggga tagcattgaa 60? Attccttc ttcttcttta cgaagtaggt gtatttaatt ttaggtcgaa gggcatt? Cc 120 cacagtaaga acctggatgg tcaagggctc tttgagaggg ctaaagctgc gaattctttc 180 caatgccgca gaggagccgc tgtacctcaa gacaacacct ttgtacataa tgtcttgctc 240 taaggtggac aaagtgtagt caccattaag aatatatgtg ccatcagcag ctttgatggc 300 aagaaagctg cccttgttcc 320 < 210 > 16 211 > 316: 212 > DNA < 213 > Eirceria tenella < 400 > 16 aatgccgaga cattaatgga cagcctgctt ccgagtgtgc aaaggaagtg aagccagcca 60 gcaccagacc ttgtgcagac catccctgcc cccagtggca gctgggsgag tggtcatcat 120 ttctaagac ctgtgggaag ggttacaaaa aaagaagctt gaagtgtctg tcccatgatg 180 gaggggtgtt atctcatgag agctgtgatc ctttaaagaa acctaaacat ttcatagact 210 tttgcacaat ggcagaatgc agttaagtgg tttaagtggt gttagctttg agggcaaggc 300 aaagtgagga agggct 316 < 210 > 17 < 2li 383 < 212 > DNA < 213 > Caenorhabditis elegans < 220 > < 221 > IT IS NOT INSURANCE < 222 > Í 1 60) < 223 > It can be any nucleic acid < 220 > < 221 > IT IS NOT INSURANCE < 222 > (326) < 223 > It can be any nucleic acid < 220 > < 22I IS NOT INSURANCE < 222 > (358) < 223 > It can be any nucleic acid < 220 > < 221 > IT IS NOT INSURANCE < 222 > (366) < 223 > It can be any nucleic acid < 220 > < 221 > IT IS NOT INSURANCE < 222 > (377) < 223 > It can be any nucleic acid < 220 > < 221 > IT IS NOT INSURANCE < 222 > (379) < 223 > It can be any nucleic acid < 400 > 17 gtcgacccac gcgtccggat ggtactccat gtagcccaga ctccacctct gtctgtgtgc 60 aaggacagtg tgtaaaagct ggttgtgatc gcatcataga ctccaaaaag aagtttgata 120 ttgcggggga aatgtggtgt aatggatcta cttgtaaaan aatatcagga tcagttacta 180 gtgcaaaacc tgggatatca tgatatcacc acaattccaa ctgggagcca ccaacatcga 240 agtgaaacag cggaaccaga ggggatccag ggaacaatgg gcagctttct tgccatcaaa 300 gctgctggat ggcacatata ttcttnaatg gtgactacac tttgtccace ttagaganag 360 383 tgt acattnt tg acaaagngnt < 210 > 18 < 211 > 404 < 212 > DNA < 213 > Crotalus atro? < 220 > < 221 > IT IS NOT INSURANCE < 2Z2 > (21) < 223 > It can be any nucleic acid < 220 > < 221 > OR IT IS SAFE < 222 > (301) < 223 > It can be any -nucleic acid < 220 > < 22 l > IT IS NOT INSURANCE < 222 > (335) < 223 > You can aer any nucleic acid < 220 > < 221 > IT IS NOT INSURANCE < 222 > (373) < 223 > It can be any nucleic acid < 220 > < 221 > IT IS NOT INSURANCE < 222 > (378) < 223 > It can be any nucleic acid < 220 > < 221 > IT IS NOT INSURANCE < 222 > (382) < 223 > It can be any nucleic acid < 220 > < 221 > IT IS NOT INSURANCE < 222 > (383) < 223 > It can be any nucleic acid < 400 > 18 cccacgcgtc cgcccacggt nccgggactt gt? Tgggtcc cagacatgtg atactcttgg 60 gatggctgat gttggaactg tgtgtgatcc gagcagaagc tgctccgtca tagaagatga 120 tggtttacaa gct? Ccttca tgaattaggc ccacagccca acatgccaca cacgtgttta 180 tgatsgatgc aaagcagtgt gccagcctta aatggtgtga accagggatt cccacatgat 240 ggcgtcaatg ctttccaacc tgggaccaca gccagccttg ggtcctcctt gcagtggccc 300 nacatggatt gacatcattt ctgggatgaa tggtncatgg gggaatgttt tgatt? Gaca 360 agccttcaga atnccctnac annttcccag gggttctccc tggg 40 < 210 > 19 < 211 > 152 < 212 > ADK < 213 Hono sapiens < 220 > < 221 > IT IS NOT INSURANCE < 222 > (105) < 223 > It can be any nucleic acid < 220 > < 221 > IT IS NOT INSURANCE < 222 > (122) < 223 > It can be any nucleic acid < 220 > < 221 > OR IT IS SAFE < 222 > "(135) < 223 > It can be any nucleic acid < 400 > 19 atcgtagaag atgaaaaatg gggcccagag gtgtccgaca atggggg t tacactgcgt 60 aacttctgca actggcagcg gcgtttcaac cagcccagcg accgpcaccc agagcactac 120 gncacggcca tcctnctcac cagacagaac tt 152 < 210 > 20 < 211 > 4180 < 212 > DNA < 213 > Unknown < 220 > < 223 > Description of the Unknown Body: Unknown < 400 > 20 gcagctccga gctaggtgct atcgcaaggc cagagegcac agcccggcgg asagagcaga 60 gatcgagtca tccttgctca aatcgggcca aggcggagga cgaagagtcc aggctcctat 120 tctggaettg ttccccagct ccgggggegc ttctaggtcc tgcagcagcc agcagtgcgg 180 agccaccaac tcggtgctgg aatgaaaaaa ttcccgcgcg atctttctaa ccagtgcaga 240 gtgacccgga gcttcgggtg ctagctctgc acgaactttc ccatcaaagt gatcgtgaat 300 tttaagcat c aggagcaggc cagcgaagct ctacgcgtct aaacgt CTAT ccagaccaag 360 agttctctgc ggt gcagggt gcggcgccat gsagccaaaa gtcccttttg ggg cacgca 420 agcagaagcc ctgctccgac atgggggacg tccagcgggc agcgagatct cggggctctc 480 t gtccgcaca catgctgttg ctgctcctcg cttccataac aatgctgcta tgtgcgcggg 540 gcscacacgg gcgccccacg gaggaagatg aggagctggt cctgccct g ctggagcgcg 600 cccgggcca c cgattccacc accacacgcc ttcgtctgga cgcctttggc cagcagctac 660 atctgaagtt gcagccggac agcggtttct tggcgcctgg cttcaccctg cagactgtgg 720 ggcgcagtcc cgggtccgag gcacaacatc tggaccccac cggggacctg gctcactgct 780 tctactctgg cacggtgaac ggtgatcccg gctctgccgc agccctcacc ctctgtgaag 840 gtgtgcgtgg tg ccttctac ctacaaggag aggagttctt cattcagcca gcgcctggag 900 tggccaccga gcgcctggcc cctgccgtgc gtcatccgca ccgaggagga cggccgcagt 960 t ccacatcct gaggcgaagg cggcggggca gtggcggcgc caagtgcggc gtcatggacg 1020 acgagaccct gccaaccagc gactcgcgac ccgagagcca gaacaccc g aaccagtggc 1080 ccccacgcci ctgtgcggga caggacgcgg gaaagccatc aggaccacga agcacaagga 1140 agaagcgatt tgtgtccagc ccccgttatg tggaaaccat gctcgtagct gaccagtcca 1200 tggccgactt ccacggcagc ggtctaaagc attaccttct aaccctgctc tcggtggcag 1260 ccaggtttta caagcatccc agcattagga attcaattag cctggtggtg gtgaagatct 1320 tggtcatata cgaggagcag aagggaccag aagttacctc caatgcagct ctcacccttc 1380 ggaatttctg cagctggcag aaacaacaca acagccccag tgaccgggat ccagagcact 1440 atgacactgc aattctgttc accagacagg atttatgtgg ctcccacacg tgtgacactc 1500 tcggaatggc agatgttgga accgtatgtg accccagcag gagctgctca gtcatagaag 1560 atgatggttt gcaagccgcc ttcaccacag cccatgaatt gggccatgtg tttaacatgc 1620 cgcacsatga tgctaagcac tgtgccagct tgaatggtgt gagtggcgat tctcatctga 1680 tggcctcgat gctctccagc ttagaccata gccagccctg gtcaccttgc agtgcctaca 1740 tggtcacgtc cttcctagat aatggacacg gggaatgttt gatggacaag ccccagaatc 1800 caatcaagct cccttctgat cttcccggta ccttgtacga tgccaaccgc cagtgtcagt 1860 ttacattegg agaggaatcc aagcactgcc ctgatgcagc cagcacatgt actaccctgt 1920 ggtgcactgg cacctccggt ggcttactgg tgtgccaaac aaaacacttc ccttgggcag 1980 atggcaccag ctgtggagaa gggaagtggt gtgtcagtgg caagtgcgtg aacaagacag 2040 acatgaagea ttttgctact cctgttcatg gaagctgggg accatgggga ccgtggggag 2100 actgctcaag aacctgtggt ggtggagttc aatacacaat gagagaatgt gacaacccag 2160 tecesaagaa cggagggaag tactgtgaag gcaaacgagt ccgccacagg tcctgtaaca 2220 tcgaggactg tecagacaat aacggaaaaa ggagcagtgc cgttcagaga gaggcgcaca 2280 atgagttttc caaagcttcc tttgggaatg agcccactgt agagtggaca cccaagtacg 2340 ccggcgtctc gccaaaggac aggtgcaagc tcacctgtga to ccaaaggc attggctact 2400 ttttcgtctt acagcccaag gttgtagatg gcactccctg tagtccagac tctacctctg 2460 tcrgtgtgca agggcagtgt gtgaaagctg gctgtg atcg tccaaaaaga catcataga 2520 'agtttgataa gtgtggcgtt tgtggaggaa acggttccac atgcaaga g atgtcaggaa 2580 tagtcactag tacaagacct gggtatcatg acattgtcac aattcctgct ggagccacca 2640 acattgaagt gaaacatcgg aatcaaaggg ggtccagaaa caatggcagc tttctggcta 2700 ttagagccgc tgatggtacc tatattctga atggaaactt cactct aka acactagagc 2760 aagacctcac ctacaaaggt actgtcttaa ggtacagtgg ttcctcggct gcgctggaaa 2820 ctttagtcca gaatccgcag ctcaaagaac ccttaaccat ccaggttctt atggtaggcc 2880 atgctctccg acccaaaatt aaattcacct gaagaagaca aetttatgaa gagtcattca 2940 acgccattcc cacattttct gagtgggtga ttgaagagtg gggggagtgc tccaagacat 3000 gcggctcagg ttggcagaga agagtagtgc agtgcagaga cattaacgga caccctgctt 3060 ccgaatgtgc aaaggaagtg aagccagcca gtaccagacc ttgtgcagac cttccttgcc 3120 cacactggca ggtgggggat tggtcaccat gttccaaaae ttgcgggaag ggttacaaga 3180 agagaacctt gaaatgtgtg tcccacgatg ggggcgtgtt atcaaatgag agctgtgatc 3240 ctttgaagaa gccaaagcat tacattgact tttgcacact gacacagtgc agttaagagg 3300 cgttagagga caaggtagcg tggggagggg ctgatacact gagtgcaaga gtactggagg 3360 gatccagtga stcaaaccag taagcagtga ggtgtggcaa ggaggtgtgt gtaggggata 3420 catagcaaag gaggtagatc aggacactac cctgccagtt acattctgat aaggtagtta 3480 atgaggcaca gtagcatctg aaagaccata aggagcccca cagagcaeta aagcactatt 3540 agtatctctt ttcttatatc tatcgcccaa ataattttca gagtctggca gaagccctgt 3600 taactagata tgcactgtac cttcttatca caaagattgg gaaaggcaaa gcagaaagat 3660 ggtaagactg ggtttcaaac aaggcttggt ttcaatcact ggaggcaagg aggaggggac 3720 aaacaagatc attattcgaa gtcgctggtt gctgtggttt tacggaaggt tgatgcatca 3780 ttcctatcaa eagtgaaaag ttcagcttgt tcaacgtgac agaaaggctc atctccgtga 3840 aagagctcct gatttcttct tacaccatct cagttcttaa ctatagttca tgttgaggta 3900 gaaacaactc atctatttat ttggaaaaaa aaaatgtaca ttatgaggta aaagtgaagt 3960 ctgaaggaaa cacataaaaa caatgagcaa catgcctcct gctttgcttc ctcctgaggt 4020 aaacctgcct ggggattgag gttgtttaag attatccatg ggcagtaaaa gctcacaaga 4080 taatacatgt tgtgccagag ttagaatggg gtatagagat cagggtccca tgagatgggg 4140 aac = tggtga tcactcatct cacatgggag gctgccgcag 4180 < 210 > 21 < 211 > 9248 < 212 > DNA < 213 > Unknown < 220 > < 223 > Description of the Unknown Body: Unknown < 400 > 21 gcagctccga gctaggtgct atcgcaaggc cagagcgcac agcccggcgg agagagcaga 60 tccttgctca gat cgagtca aatcggggcc aaggcggagg acgaagagtc caggctccta 120 ttctggactt gttccccagc tccgggggcg cttctaggtc ctgcagcagc caggagtgcg 180 gagccaccaa ctcggtgctg gaatgaaaaa attcccgcgc gccagtgcag aatct ttcta 240 agtgacccgg agcttcgggt gctagctctg cacgaacttt cccatcaaag tgatcgtgaa 300 tttcaagcat caggagcagg ccagcgaagc tctacgcgtc taaacgtcta tccagaccaa 360 gagttctctg cggtgcaggg tgcggtgcca tgcagccaaa agcccctttg gggtcacgca 420 agcagaagcc ctgctccgac atgggggacg tccagcgggc agcgagatct cggggctctc 480 tgtccgcaca catgctgttg ctgctcctcg cttccataac aatgctgcta tgtgcgcggg 540 gcgcacacgg gcgccccacg gaggaagatg aggagctggt cctgccctcg ctggagcgcg 600 ccccgggcca cgattccacc accacacgcc ttcgtctgga cgcctttggc cagcagctac 660 atctgaagtt gcagccggac agcggtttet tggcgcctcg cttcaccccg cagactgtgg 720 ggcgcagtcc cgggtccgag gcacaacatc tggaccccac cggggacccg gctcactgct 780 tctactctgg cacggtgaac ggtgatcccg gctctgccgc agccctcagc ctctstgaag 840 gt gtgcgtgg tgcc ttctac ctacaaggag aggagttctt cattcagcca gcgcccggag 900 tggccaccga gcgcctggcc cctgccgtgc ccgaggagga gtcatccgca cggccgcagt 960 tccacatcct gaggcgaagg cggcggggca gtggcggcgc caagtgcggc gtcatggacg 1020 acsagaccct gccaaccagc gactcgcgac ccgagagcca gaacacccgg aaccagtggc 1080 ctgtgcggga ccccacgcct caggacgcgg gaaagccatc gtgaccccca aggtataaga 1140 tctctcagtc cttacgaggc gtgacttggg gtcacactcc agatcgcctc taaatgcgaa 1200 tgactcagac ttgcagtgaa ttgaagttct gggtcgtgac cttcccgatc cccccccccc 1260 aaaaaaagtg tgaccatact ctgctagaac acttatttgc ccgaat = gtt aataatttga 1320 aagaatcgga gaaagagaga ggtcctgtag ataagggcta agcgtttoct ccgcgaagcc 1330 aataacccga ctccttacac tggagaatct ctctccatcc ctttaatgcc tttagtgaat 1440 gtatgagttc actttaacta ggttgtagtt tcgcgctgag ttttgtaacg tcagtccgtg 1500 tgagcacgta gcgctcaaag gagggcggag tagaggagcc atggtgacct ggatgtgcgt 1560 tcaggagcct gggcaacggc agtggtgatc tcatttctgt ggccttccgt ctgtcccctt 1620 cccccatttg aaaagctgac cccgatggct ggtggctccg ttgggcccct ctgcagaacc 1680 tgcttgggag gtctttgctt ggttcgcccc gcctccacgc gcctcctacc tcggcctcgt 1740 tgctcgcact ccctctcccg gcagaggttg gactccccag cgctgtggaa tgttagcctg 1800 gactgatcct ccctgctaca cattcgcctg actctgccgt gttcagtctc taccagccag 1860 ttagttcttt ttaatcattc aaatttcttt ttgccctttt ctagatttct ccctcttttc 1920 cgacttgtcc ctaggagctg gtattcatat cctactttac gatttctctg accgctgagt 1980 ctcagcagcc cgaaaaaggc cattttccaa attggcaacc ctggtttgag aaaggaactt 2040 attccccccg gggcactggg agtgagagga ggcaggaaaa cactgctggg cagagtgggt 2100 ggtcctagtg cccggaactg gatcaagcag agaaccccct gggacccctt gaatgagaga 2160 gctgagcctt acagactgag actcctcaag ccccacccct tggctgagct ccccgccctg 2220 ccccatgcct tccacgtgga gctggatgat ctcattcggg atttcagccc tggcttcaat 2280 agtgaaaggg tgactcaggg cgtccgcctg cttctcttgc caagttttta ctacagctgg 2340 tagccatact gtagaaatga gcctcactca tcttcaaaga ggctgtggag ccacaaaaga 2400 cacatatata aatctgcgga gacagtttga tcactctgtt gcttgctttg ttttgttttg 2460 tttaaagcaa ttttgtctta aagaaaaaag acttaaaaat aactcacagt ttttagaaga 2520 tgcaaatatt tgttttattt ttgttc CAGG tgtatttcag ttttatttac tttgactagg 2580 ttgactttcc taatataccc cgagaaggtc actattagga gaaggactgc ccatgagcaa 2640 acttcctttt ctttttacag gaccaggaag cataaggaag aagcgatttg tgtccagccc 2700 ccgttatgtq gaaaccatgc tcgtggctga ccagtccatg gccgacttcc acggcaqcgg 2760 tctaaagcat taccttctaa ccctgttctc ggtggcagcc aggttttaca agcatcccag 2820 cattaggaa t tcaattagcc t ggtggtggt gaagatct tg gtcatatatg aggagcagaa 2880 gttacctcca gggaccagaa atgca? CTCT aatttctgca cacccttcgg actggcagaa 2940 acaacacaac agccccagtg accgggatcc agagcactat gacactgcaa ttctgttcac 3000 cagacaggta agacaggagc ttatcaacca tttcatcaac tcaactcgga ggtcagcctt 3060 gtgttggatg ggatgagagg gtgggggtgt ggcggagagg ggggatgaca aaacccagaa 3120 tttgaaatgt aaacaaaata accaattaaa aaaaaaaggc atctcatctg tattgcctca 3180 tttcctttcg gttataggct agctcaatct gtcttgctta tttctatttt aaacttccac 3240 atctcaa_gtt ctacagttct attttaaaag cattacaggg aatcttgctt agagtcagtc 3300 cttcaagccc agcaataatg aatggacagg cttcaaagtg catgtgaaga cacgcccaac 3360 tgaagagcta agtatcactc tctcctactt aaaagggatt tcccttgcct ctttgtagga 3420 TTTA gtggc tcccacacgt gtgacactct gatgttggaa cgggatggca ctgtatgtga 3480 ccccagcagg agctgctcag tcatagaaga tgatggtttg caagccgcct tcaccacagc 3540 ccacgaattg ggtaagtcgg cttcagagta caagttaagc ccaaatgcat ggatacaacc 3600 atctgatgtg caataagtca aaacatctca acgagagaga gactatgttg ctacctcagc 3660 caccagcaat tttagaaggg ttttccacga gtagggtata tttcaagtat ggtcttacta 3720 ggacaggaga "aagtggtaca aacatttgaa cgttgacatt tttatacttg ccctgatcaa 3780 agtgagtatg agccccaata caggttgtct aataagagag ccattgagcc tcactcaata 3840 atacagctga atgtccttct tgtctgcttc ccaggccatg tgtt taacat gccgcacgat 3900 gatgctaagc actgtgccag cttgaatggt gtgactggcg attctcatct gatggcctcg 3960 gcttagacca atgctctcca tagccagccc tggtcacctt gcagtgccta catggtcacg 4020 tccttcctag ataatggaca cggtaagatg acagctcctc tttccagatg gtgttcaacc 4080 ttccttg'tgt agg gctctct ctggctaagt gagctccatg gctcttgctc atttcccctc 4140 cttcagagtt ttctctggca ggatcataag tagtagatct ttacctccat tgcatcctgc 4200 cattcattca tcccaaagtc taaacaataa cttctcgcca ttgtaaaatc agaagtcccc 4260 tattgaggat aacgtctcga taaaaatcta aagttcccta gcat tgattt tcccaaaaat 4320 gcatgatttc accaaacatg tattaataat tgcctctttt ttcttttcct tttttttttt 4380 tattatttta ggggaatgtt tgatggacaa gccccagaat ccaatcaagc tcccttctga 4440 tcttcccggt accttgtacg atgccaaccg ccagtgtcag tttacattcg gagaggaatc 4500 caagcactgc cctgatgcag ccagcacatg tactaccctg tggtgcactg gcacctccgg 4560 t? gcttactg gtgtgccaaa caaaacactt gatggcacca cccttgggca gctgtggaga 4620 agggaagtgg tgtgtcagtg gcaagtgcgt gaacaagaca gacatgaagc attttgctgt 4680 gagttttccc aatgaaacat atccgtttgc aactcagggt tgagaagggc aaagtgatgg 4740 ttcctagaca tttagttcct aactcctcta cctgtgtcct gtagtgggae tatgagatgg 4800 tagcgtattt tgagaattga ttgtctgttt tacatttttc tctgatcccc taaaatgtct 4860 ttatagttct aacactgata tetgtatctc catttagact cctgttcatg gaagctgggg 4920 accatgjgga ccgtgggg ag actgctcaag aacctgtggt ggtggagttc aatacacaat 4980 gagagaatgt gacaacccag tcccaaagaa cggagggaag tactgtgaag gcaaacgagt 5040 ccgctacagg tcctgtaaca tcgaggactg tccagacaat aacggtgagt catactggac 5100 ttcagctctc agaaaccggg caaaggcggc gtgccacaac atgtggttgg aagttggaaa 5160 crgggaacat catcgcc? tc gttctctttt caggaaaaac gttcagagag gagcagtgc? 5220 aggcgcacaa tgagttttcc aaagcttcct ttgggaatga gcccactgta gagtggacac 5280 ccaagtacgc cggcgtctcg ccaaaggaca ggtgcaagct cacctgtgaa gccaaaggca 5340 ttggctactt tttcgtctta cagcccaagg taggtgcttt tacacttgaa tctttgcaaa 5400 ggagcctcag ctgggcttgc tgccatgcca tacaaacgtt tgggctgcct ttacctattg 5460 atctgtgttc cgttttgaat ttggaatact tctaaatgca ggaacaactc cttgctttgg 5520 gatttgttgt tgccttctgt tgggaaggaa gcttaaatct agctagcact taaaagagtc 5580 ttgcatgtgt ttaatattgc ttctctatcc ccaaagaatg gccctttgaa aactcaagag 5640 ccctctctgt ataactaggt ttcacataca aaaattcatg gttagataaa ttatatatta 5700 acatggcacc caggagtttt agaaagtagt ccaaagtact tgttactggg tacctagcag 5760 gagcacacta ccgcacatac actaaggtaa attaaaaatt gagtttgaga catcgttgga 5820 tgaccaaaga acatgtactt gactcgccat ttcttttggt gttttgcaga aaggataaat 5880 cctgctttga agaagaaaat tgaatgaaat ttgcttaagc ttgtcacgta t ccttagcat 5940 tataagatag caaactatat ccaagttgtg gatgaagtat ttagcsagtg att tataaag 6000 taccttcaac tacagcatat tattctaggt actgaccatg gaacaataat cagtgtgaca 606 0 gtgaaccctg cttccattga cctaggccag caaatatata aaatcaagac att tataagc 6120 gctatatgaa cttacagata ctgttgaaaa agecaaaatg aaagtgaaca tgtggcacgt 6180 gacaaggaga ctacttgtag cctgggagga gagcattccc agttgccatc acatcagatg 6240 tttaaccacc atggtgcatg ttgtctccac aggttgtaga tggcactccc tgtagtccag 6300 actctacctc tgtctgtgtg caagggcagt gtgtgaaagc tggctgtgat cgcatcatag 6360 actccaaaaa gaagtttgat aagtgtggcg tttgtggagg aaacggttcc acatgeaaga 6420 agatgtcagg aatagtcact agtacaaggt gagtttcaga acgctcactt ctgcagtaga 6480 cacgctgtgt tgctcagttg gtccctagca tetacaagac cttgggrtca atccgcatgc 6540 atgeacctgt agtcccagtg tatgggagac agagacaagt gtgac = agac ggtcagatgt 6600 tcaggtcatc tttgctasat agtgactttc agttcacctt ggggaacatg aaaaacctga 6660 ct ggaaacac aaacacacac aaaacaatta acccaggtac ttcatgtaat cccagtgttc 6720 cttgggagga agtaggctga tggttgctat aaggcctagg ttagcttggt ctacataatg 6780"gctccagta taacctggcc cacaagtgaa ccctaaagtt aattaatega cacatgaaac 6840 aaaacacatg ctttggagac cctgtaattt tgatataega ttttg Agga ctaaggaaaa 6900 gtcacatt ta aaagaattgc ctatttttaa agcaatgtga ttgattaact cattgaaaga 6960 cazataectg ttttctttgc ccacag = cct gggtarcatg acattgtcac aat TCCT ct 7020 ggagccacca acattgaagt gaaacatcgg aatcaaaggg ggtccagaaa caatggcagc 7080 tttct ggcta ttagagccgc tgatggtacc tatattctga atggaaactt cactctgtcc 7140 acactagage aagacctcac ctacaaaggt actgtcttaa ggtacagtgg ttcctcggct 7200 gcgctggaga gaatccgcag ctttagtcca ctcaaagaac ccttaaccat ccaggttctt 7260 atggtaggcc atgctctccg acccaaaatt aaattcacct actttstgaa gaagaagaca 7320 gagtcattea acgccattec cacattttct gagtgggtga ttgascagtg gggggagtgc 7380 t ecaagacat gcggctcagg ttggcagaga agagtagtgc agtgeagaga cattaatgga 7440 caccctgctt ccgaacgtgc aaaggaagtg aagccagcca gtaccagacc ttgtgcagac 7500 cacactggca cttccttgcc ggtgggggat tggtcaccat gttccaaaac ttgcgggaa 7560 ggttacaaga agagaacctt gaaatgtgtg tcccacgatg ggggcgtgtt atcaaatgag 7620 agctgtgatc ctttgaagaa gccaaagcat tacattgact tttgcacact gacacagtgc 7680 agctaagagg cgttagagga caaggtagcg tggggagggg ctgatacact gagtgctgga 7740 gggatccagt gagteaaace agtaagcagt gaggtgtggc aaggaggtgt gtgtagggga 7800 aggaggtaga tacatagcaa tcaggacact accctgccag ttacattctg ataaggtagt 7660 taatgaggca cagtagcatc tgaaagacca tacagagcac taaggagccc caaagcacta 7920 ttagtatctc ttttcttata tctatcgccc aaataatttt cagagtctgg cagaagccct 7980 gttgcactgt actgactaga tacttcttat cacaaagatt gggaaaggca aagcagaaag 8040 tgggtttcaa atggtaagac gtttctatca acaaggcttg ctggaggcaa ggaggagggg 8100 acaaacaaga tcattattcg aagtcgctgg ttgctgtggt tttacggaag gttgatgcat 8160 aacagtgaaa cactcctatc agttcagctt gttcaacgtg acagaaaggc tcatctccgt 8220 gaaagagctc ctgatttctt cttacaccat ctcagttctt aactataatt catgttgagg 8280 tagaaacaat tcatctattt ataaaatgta cattgg yyyy aaaaaagtga agtttatgag 8340 gtacacataa aaactgaagg aaacaatgag caacatgcct cctgctttgc ttcctcctga 8400 ggcaaacctg cctggg? att gaggttgttt aagattatcc atggctcaca agaggcagta 8460 tgttgtgcca aaataataca gagttagaat ggggtataga gatcagggtc ccatgagatg 8520 gggaacatgg tgatcactca tctcacatgg gaggctgctg cagggtagca ggtccactcc 8580 tggcagctgg tccaacagtc gtatcctggt gaatgtctgt tcagctcttc tactgagaga 8640 gaatatgact gtttccatat gtatatgtat atagtaaaat atgttactat gaattgcatg 8700 tactttataa gtattggtgt gtctgttcct tctaagaagg actatagttt ataataaatg 8760 cctataataa catatttatt tttatacatt tatttctaat gataaaacct ttaagttata 8820 tcgcttttgt aaaagtgcat ataaaaatag Agta ttata caatatatgt taactagaaa B880 taataaaaga acacttttga atgtgtatgc ctattttctg gagtgggatt aacttctggg 8940 gatgagacac caagaaatct aaacattgga ettcaagaca gttttaaaat ttgggcaaat 9000 SAGs gtatt tcctgtttat agacgtacta ataaaaaaga agttgatga gtctttagtg 9060 gtaagettgt tactaatgtg gttggcaaat tgctgtaaag agccagatag taagcattta 9120 tggca tgta ggctatcttt cctgccacaa ccat? tgaca g tgagtgctt tgtaggactg 9180 agagcagcca taaatgacat gtaaatgata aactgtggct gtgctttaat aaaactttat 9240 ttacaaaa 4ñ < 21C > 22 211 > 5722 < 212 > DNA < 213 > Unknown < 220 > < 223 > Description of the Unknown Body: Unknown < 400 22 ggacgcacag gcattccccg cgcccctcca gccctcgccg ccctcgccac cgctcscggc 60 cgccgcgctc cggtacacac aggatccctg ctgggcacea acagctccac catggggctg 120 gcctggggac taggcgtcct gttcctgatg catgtgtgtg gcaccaaccg cattccagag 180 tcfcggcggag acaacagcgt gtttgacatc tttgaactca ccggggccgc ccgcaagggg 240 cetcggcgcc gactggtgaa gggccccgae CCIT CAGCC cagctttccg catcgaggat 300 gccaacctga tcccccctgt gcctgatgac aagttccaag acc ggtgga tgctgtgcgg 360 gcagaaaagg gtttcctcct tctggcatcc ctgaggcaga tgaagaagac ccggggcacg 420 ctgctggccc tggagsggaa asaccactct ggccaggtct tcagcgtggt gtccaatggc 480 aaggcgggca ccctggacct cagcctgacc gtccaaggaa agcagcacgt ggtgtctgt? 540 gaagaagctc tcctggcaac cggccagtgg aagagcatca ccctgtttgt gcaggaagac 600 agggcccagc tgtacatcga ctgtgaaaag atggagaatg ctgagttgga cgtccccatc 660 tcaccagaga caaaccgtct cctggccagc atcgccagac tccgcatcgc aaaggggggc 720 gtcaatgaca atttccaggg ggtgctgcag aatgtgaggt ttgtctttgg aaccacacca 780 gaagacatcc tcaggaacaa aggctgctcc agctctacca gtgtcctcct cacccttgac 840 aacaacgtgg gaatggttc cagccctgcc atccgcacta actacattgg ccacaagaca 900 aagcacrtgc aagccatctg cggcatctcc tgtgatgagc tgtccagcat ggtcctggaa 960 ctcaggggcc tgcgcaccat tgtgaccacg ctgcaggaca gcatccgraa to? tgactgaa 132C gagaacaaag agttggccaa tgagctgagg cggcctcccc tatgctatca eaacagagtt 1080 ataacgagga cagtacagaa atggactgtt gatagctgca ctgagtgtca ctgtcagaac 1140 tctgcaaaaa tcagttacca ggtgtcctgc cccatcatgc cctgctccaa tgccacagtt 1200 cctgatggag aatgct? aka tcgctgttgg cccagcgaet ctgcggacga tggctggtct 1260 ccatggtccg agtggaeete ctgttctacg agctgtggca atggaattca gcagcgcggc 1320 cgctcctgcg atagcctcaa caaccgatgt gagggctcct cggtccagac acggacctgc 1380 cacattcag g agtgtgacaa aagatttaaß caggatggtg gctggagcca ctggtecccg 1440 tggtcatctt gttctgtgac atgtggtgat ggtgtgatca caaggatccg gctctgcaac 1500 tcccccagec cccagatgaa tgggaaaccc tgtgaaggcg aagcgcgg? a ^ tgcaag gaccaaagcc 1560 aag acgcctgccc catcaatgga ggctggggtc cttggtcacc atgggacatc 1620 tgttctgtca cctgtggagg aggggtacag aaacgtagtc gtctctgcaa caaccccgca 1680 ccccagtttg gaggcaagga ctgcgttggt gatgtaacag aaaaccagat ctgcaacaa? 1740 caggactgtc caattgatgg atgcctgtcc aatccctgct ttgccggcgt gaagtgtact 1800 agctaccctg atggcagctg gaaatgtggt gcttgtcccc ctggttacag tggaaatggc 1860 cagatgttga atccagtgca tgagtgcaaa gaagtgcctg at gcctgctt caaccacaat 1920 ggagagcacc ggtgtgagaa cacggacccc ggstacaact gcctgccctg ccccccacgc 1980 ttcaccggct cacagccctt cggccagggt gtcgaacatg ccacsgccaa caaacaggtg 2040 tgcaagcccc gtaacccctg cacggatggg acccacgact gcaacaagaa cgccaagt gc 2100 aactaectgg gccactatag CGA ccccatg taccgctgcg agtgcaagcc tggctacgct 2160 ggcaatggca tcatctgcgg ggaggacaca gacctggatg gctggcccaa tgagaacctg 2220 gtgtgcgtgg ccaatgcgac ttaccactgc aaaaaggata attgccccaa ccttcccaac 2280 aagactatga tcagggcagg caaggatgga attggcgaeg cctgtgacga tgacgatgac 2340 ttccagatga aatgataaaa cagggacaac tgtccattcc attacaaccc agctcagtat 2400 gactatgaca gagatgatgt gggagaccgc tgtgacaact ccacaaccca gtccctacaa 2460 gat caggcag caatggggaa acacagacaa gtgctgcaga ggagacgcct cattgatgga 2520 gacggtatcc tcaatgaacg ggacaactgc cagtacgtct acaatgtgga ccagagagac 2 580 actgatatgg atggggttgg agatcagtgt gacaattgcc ccttggaaca caatccggat 2640 ctgactcaga cagctggact ccgcattgga gatacctgtg acaacaetca ggatattgat 2700 gaa atggcc accagaacaa tctggacaac tgtccctatg tgcccaatgc caaccaggct 2760 aagatggcaa gaccatgaca gggagatgcc tgtgaccacg atgatgacaa cgatggcatt 2820 cctgatgaca aggacaactg cagactcgtg cccaatcccg accagaagga ctctgacggc 2880 gatggtcgag gtgatgcctg caaagatgat tttgaccatg acagtgtgcc agacatcgat 2940 gacatccgtc ctgagaatgt tgacatcagt gagaccgatt tccgccgatt ccagatgatt 3000 cctctggacc ccaaagggac atcccaaaat gaccctaact gggttgtacg ccatcagggt 3060 aaagaactcg tccagactgt caactgtgat cctggactcg ctgtagscta tgatgagttt 3120 aatgctstgg acttcagtgg caccttcttc atcaacaccg aaagggacga tgactatgct 3180 ggatttgtct ttggctacca gtccagcagc cgcttttatg ttgtgatgtg gaagcaagtc 3240 acccagtcct actgggacac caaccccacg agggctcagg gatactcggg cctttctgtg 3300 aaagttgtaa actccaccac agggcctggc gagcacctgc ggaacgccct gtggcacaca 3360 ggaaacaccc ctggccaggt gcgcaccctg tggcatgacc ctcgtcacat aggctggaaa 3420 gatttcaccg cctacagatg gcgtctcagc cacaggccaa agacgggttt cattagagtg 3480 gtgatgtatg aagggaagaa aatcatggct gactcaggac ccatctatga taaaacctat 3540 gctggtggta gactagggtt gtttgtcttc tctcaagaaa tggtgttctt ctctgacctg 3600 aaatacgaat gtagagatcc ctaatcatca aattgttgat tgaaagactg atcataaacc 3660 aatgctggta ttgcaccttc tggaactatg ggcttgagaa aacccccagg atcacttctc 3720 cttggcttcc ttcttttctg tgcttgcatc agtgtggact cctagaacgt gcgacctgcc 3780 tcaagaaaat gcagttttca aaaacagact catcagcact cagcctccaa tgaataagac 3840 atcttccaag catataaaca attgctttgg tttccttttg aaaaagca c tacttgcttc 3900 agttgggaag gtgcccattc cactctgcct ttgtcacaga gcagggtsct attgtgaggc 3960 catctctgag cagtggactc aaaagcattt tcaggcatgt cagagaaggg aggactcact 4020 aacaaaacca agaattasca ctccttcagg ccctgacatc gcagaggcca aacacgggga 4080 AAGC = ctaag gggagggcgc ataccc gaga cgattgtatg aagaaaatat ggaggaactg 4140 ttacatgttc ggtactaagt cattttcagg ggattgaaag actattgctg gatttca ga 4200 tgctgactgg cgttagctga ttaacccatg taaataggca cttaaataga agcaggaaag 4260 ggagacaaag actggcttct ggacttcctc cctgatcccc acccttactc atcaccttgc 4320 agtggccaga attagggaat cagaatcaaa ccagtgtaag gcagtgctgg ctgccattgc 4380 ctggtcacat tgaaattggt ggcttcattc tagatgtagc ttgtgcagat gtagcaggaa 4440 aataggaaaa cctaccatct cagtgagcac cagctgcctc ccaaaggagg ggcagccgtg 4500 tatggttaca cttatatttt attattatca atggeaeaaa acctaactaa aacattcctt 4560 ttctcttttt tccgtaatta ctaggtagtt ttstaattct ctcttttgga agtatgattt 4620 ttttaaagtc tttaegatgt aaaatattta ttttttactt attctggaag atctggctga 4680 aggattattc atggaacagg aagaagcgta aagactatcc atgtcatctt tgttgagagt 4740 cttcgtgact gtaagattgt aaatacagat tatttattaa ctctgttctg cctggaaatt 4800 taggcctcat acggaaagtg tttgagagca agtagttgac atttatcagc aaatctcttg 4860 acaaggaaaa caagaacagc tcagtctaat aagctgctct gccccttgtg ctcagagtgg 4920 atgttatggg attccttttt tctctgtttt to tcttttcaa gtggaattag ttggttatcc 49B0 atttgcaaat gttttaaatt gcaaagaaag ccatgaggtc ttcaatactg ttttacccca 5040 tccc tgtgc atatttccag ggagaaggaa agcatataca cttttttctt tcatttttcc 5100 aaaatgacaa aaaagagaaa aaggtgaaac ttacatacaa atattacctc atttgttgtg 5160 tgactgagta aagaattttt ggatcaagcg gaaagagttt aagtgtctaa caaacttaaa 5220 gctactgtag tacctaaaaa gtcagtgttg tacatagcat aaaaactctg cagagaagta 5280 ttccc = ataa ggaaatagca ttgaaatgtt aaatacaatt tctgaaagtt atgttttttt 5340 tctatcatct ggtataccat tgctttattt ttataaatta ttttctcatt gccattqgaa 5400 tagaatattc agattgtgta gatatgctat ttaaataatt tatcaggaaa tactgcctgt 5460 agagttagta tttctatttt tatataatgt ttgcacactg aattgaagaa ttgttggttt 5520 tttctttttt ttgttttttt tttttttttt tttttttttg cttttgacct cccattttta 5580 ctatttgcca ataccttttt ctaggaatgt gctttttttt gtacacattt ttatccattt 5640 agcagtgtaa tacattctaa gttgtatatt actgtttctt atgtaca = gg aacaacaata 5700 5722 tt aatcatatgg aaatttatat < 210 23 < 211 > 42521 < 212 > DNA < 213 > Unknown < 220 > < 223 > Description of the Unknown Body: Unknown < 400 > 23 gatcgttttc cagacatttt tgttctctgt tcatttcctt atcgtattca aaaagttatc 60 acaaatgacc ttctctatct gtctgcgtct cttttaactc tcaccgtttg ggacctttca 120 aatagctttt cgctatcaaa tctaaacatt agttgcgttg actcgacatt tgacccctca 180 ctatcatctc cagttctctt ttttgttaca ctttagcagt ggcagcagag agcaagtagg 240 gtgtgcgcca tggagccaaa aaaattgtgt ttcatcggga attttgggca tcttcatcaa 300 atttactcgg gatttgcgct aatttggaaa caaaaattca aattcctgcc aattgtttcg 360 tttgcttttt ttcttttttt tttgctcctc ccatctctca tcaaattgct cttttttcga 420 ttctaacata tcagccatct tcagagtgtg tcactaaccc ccatttttat tcaaggttag 480 tgatatagta tcctaactac agacgtcaca ccatgaggtt gctgctctte tcggcagccc 540 ttcttctgtg ctccgtccca acgtgggcct tctctctgtc atcattcttc ggaaqcgatg 600 ttgcacaagt aagcaagctc tcctatacct agaatcttgt aaattgaaaa ctctaatttc 660 cagaagccat accttcatcc aaactcccca ccggsgcgtg acccggcgag ttccagaatg 720 aagagacagg catatcaagt gtacgttgat ggagatgttt ccgttactgt tgacaagtct 780 ggacaaaagg aaaccggcaa ctggggacca tgggtgcccg agaacgagtg ctcacgttc? 840 tgtggtggag gagttcaact cgagaagaga cagtgcaggt tcgtggactt ttcatttttt 900 agggaatttc ctagacgttc taaaagctta ttttcaaaaa ttttggtttc ctgatcttca 960 tgcctttatg aacgtggtga aagatcaacc taggctagcc tgtgacatac attttttgaa 1020 gcagatccaa ctttatcaag agccatcgaa ttctcgtttt aaagtgtttt ttttttctga 1080 taactttttt ctaatagctt tacccatttt ctgaaagcaa tatgtcaaga tgaatcacaa 1140 gaggctatct acgtttgttt ttgaagctct gtaggaatca tcttaaaaaa ttaagtaaag 1200 taatggagat gaaattctaa ttttttaaaa tcataatcat tactttccct attatcttca 1260 agttcaaact tttcaaacgg ttattctcaa tagaatttta gaaactcaca acaatttcct 1320 cttgcaagca ctatctattt acccaccgaa ctcaaatctt atccaaacta aacttttagt 1380 ggtgactgca ctggagcttc agtccgctac atctcgtgta acttgaacgc atgcgagtct 1440 ggtactgatt tccgtgctga gcaatgctcc aaattcaacg atgaggctct tgatggaaac 1500 taccacaagt ggactccata caagggaaag aacaagtaag ttaactttct tcaagatgtt 1560 tttctaattt tcgagttttc aggtgcgagc tsgtctgtaa gccagaatct ggaaacttct 1620 actacaa'gtg ggctgataag gttgttgatg gaaccaagtg cgactccaag agcaacgata 1680 tc tgtgctga tggggaatgt cttccagttg gatgtgacgg aaagcctgga tcttgtaagt 1740 ttaaaattta attcaaaatc ttcatttcat gccgaatatt tcagctctca aattcgacaa 1800 gtgcggaaag tgcgatggag atggttctac ctgcaagact attgaaggac gtttcgatga 1860 gcgcaatctc tctccaggat accatgatat tatcaaactt ccagaaggag ccaccaacat 1920 ta = gattcag gaagccagaa agagcaccaa caacttggct ctgaagaacg gttccgatca 1980 cttttatttg aatggaaatg gattgatcca agttgagaag gaggttgaag tcggaggaac 2040 tatcttcgtt tacgatgacg ctgaaccaga aactctcagt gcteaaggac cactctccga 2100 ggagctcacc gttgctcttc tcttcagaaa gggaagccgt gatactgcta tcaagtacga 2160 gttctctatt ccacttgagg aggaagttga ctacatgtac aagtttgaca actggactcc 2220 tcatgcggaa gtgctctgta aacccgtaat agggtgttca ttgatggaaa ctctactgta 2280 gaacaaggga cgcgttgagg atgatctctg cgaggagaac aatgccacaa agccagagtt 2340 cgaaaagagc tgtgaaactg ttgactgtga agccgaatgg ttcactggag actgggaatc 2400 ttgctcatcc acctgcggag atcaaggaca gcaatacegt gtcgtetact gccatcaagt 2460 attcgctaac ggacgtcgtg ttaccgttga ggatggaaac tgcaccattg agagaccacc 2520 agtaaagc ag acttgcaatc ggtaagttga ttttataaat gcataascaa ctctgtgaat 2580 ctatttgttt atgcgatgct atccatatat attaccagat ggtgttggtg cccaaaactt 2640 ATAA CAATT attttctctt tgcagttttg cctgcccaga gtggcaacct ggtccgtggt 2700 cggcttgctc agagaagtgt ggagacgcct tccaatacag atcggtgacc tgcegcagtg 276C -agaaggaagg agaagaggga aaactcttgg ccgctgatgc ttgcccagct gatsagcaag 2820 cacagagaga agaagttcga acttgcaatt tgggaccatg cgagggacct acatttgtca 2880 ctggagaatg gaacttggtt agattttgca aaatatgggg acctggggas aagcatacta 2940 actttatgaa aataagatca acaaataatt tttagtgcac ccgctgcaac gatactgagg 3000 agactcgtga agtcacctgc aaggactccc aaggaagagc ctatccactc gagaagtgtt 3060 tggttgataa ctccaccgag attccaactg atactaggtg agtcattcca gatatgacat 3120 tgaacttgga ttaatttttt tcttccagat catgcgccac ccaaccacca tgtgagtacg 3180 agtggaccgt cagtgagtgg agcaagtgta ccaccgaatg cggacacgga cacaagactc 3240 gtcgtgttat ctgtgccatc caccaaaacg gaggactcga ggttgttgat gaaggacact 3300 gaagccagaa gtcaagctga ggaaagacta actgcaccaa tgaggagaag tgtactggaa 3360 catggtacac atcttcatgg tccgagtgta ccgctgaatg tggtggtgga tcccaagatc 3420 gtgtcgctgt ttgcttgaac tacgataaga agccagttcc agaatggtgc gacgaagccg 3480 tcaagccatc tgagaaacaa gattgtaacg ttgatgactg cccaacttgc gttgactctg 3540 agttcggatg ctgcccagat aactctactt ttgctaccgg agaattcaac ttcggatgct 3600 ctaactgctc ggaaacagaa ttcggatgct gtgctgacaa cgttaccgtt gccactggac 3660 gggatgcgaa ctaactccaa gaattcgttg agtctccact taaccttgaa gctgatgttg 3720 ccaatgctga cgctgaagct tcaggagatg ctccagaact ctgcagcgtc acaaacgaga 3780 acggagaagc tgttgatgtt gagtgtgcca ccattgctcc aatcactgct cttcttggag 3840 atggggaact tatcggaaat gatactgatg gaccatacac cttccaatga tgctcgaaga 3900 atgctgtcca ccgaattcgg gattggtaca ccgccgcctc tggaaagg t aacgaaggat 3960 gcccatcgtt cactcttgga ggatgtaacg agactcaatt cggatgttgt cacgatgatg 4020 tcactcttgc tcgtggagcc aaccttgaag gatgcggaga gccatcttce gccgcttccc 4080 tctatggatg ctgtaaagat cgtaag ACAA ttgccttcgg accacactat tctggatgtg 4140 agcgatcatc cttcccatgt gagcttagcg acttcggatg ctgcccagat ggtgagactg 4200 ctgctcttgg aaagaatgga accggatgcg gagagaactg cttgaccacc aagttcggat 4260 gct ccctga tggaaagacc accgccaagg ggtcccacaa cgagggatgc ggatgcgagt 4320 tcgcccaata cggatgctgc ccagacggaa aatcagttgc caasggagcc gsattttacg 4380 gatgcccaga aagctgcgcc cagagccagt tcggatgctg cccagacgga aagactcgtg 4440 gaacaaggaa ctcgcggaga ggatgtccat gccagtacac ccgttacgga tgctgcccag 4500 atggggagac tactgctctt ggaccacgca atgatggatg tgataactgc cgctacgcca 4560 agcacggatg ttgcccagat ggagagacca aggctcttgg accagatgga gccggatgcc 4620 cacgccacca caccaactac ttcctcatgg gaggaactgt tgccccacat aaaatcgccg 4680 gacacaagaa cctgtaatca agtggaaccg tctgcggagc cggatacaag cttgtaagta 4740 tgaaaaagaa attaacctca ttggagcaac acatttcatg tataaatatt tcaatttcag 4800 gcatggcatt atgataccac tgagggacgt tgcaaccagt tctggtacgg aggatgcggt 4860 ggasatgaca acaactttgc tagccaggat atgtgcgaga cgaaccacca ctatctgcgt 4920 ggcaagggaa gatgttacct gccacgtgtt gatggaccac tccggtgtga ccaacttcag 4980 attatgatca ccaagatact ttccaagaag cactgtgtgg ccttctggtg gagaggatgt 5040 ctcggaaatg ccaacaactt caactctttc gaagaatgct ccatgttctg taaggacgtt 5100 ggaccgtacg atgctccaac caccgctgct ccaccaccac caccacagca aaatgctcag 5160 caactccaga caataccttc agttcaacag attgagattc gcaacctcaa aatctgctga 5220 cacaacaaca ccacaacagc gcaacagcaa aaccacagca caacagcaac accacgtcaa 5280 tcaatggaag acatctgcag atcccgccaa gacgccggac catgcgagac ttactccgat 5340 caatggttct acaacgcttt cagccaagaa tgcgaaacct tcacttatgg aggatgtgga 5400 gcaaatetca atcgtttccg cagcaaggat gaatgcgagc agcgttgttt cttcgttcac 5460 gga? c CAGC catccgctgc ccggcaggaa caagctcagc cagcagctca accagctcaa 5520 ccagctcagc caagtaacat cgtctctcca ccacaacagt cagctagtcc agttgtggtt 5580 ccatgtaagt tctttagaat gcatttattt cttactataa gtttctataa gttcgcatgt 5640 gaagcatccc catttcagcg aacagcaaac aacgcgatgc ttgccacctc aacgttgacc 5700 aa gacgttg taagggggct ttt? actcct ggtactacga agttgccacc ggatcctgcg 5760 tcacattcaa gtaeaccgga tgcggaggaa acgcca ACAG atttgctagc aaggatcagt 5820 gcgagtcact ctgtgtgaag ccagcttctg aagetgcttc agccggaatt ggtatgcttt 5SS0 gagttataga gaatgttcac tatttttgtt aaatgtttga gtaaata = ga aactggct = 5540 gtttgaaaat gtttgcacca tgtttcaaaa tagtttttga gttgaac = gt tgaggccatg 6C00 aaaatcttaa ttacactcca gaagtacatt ttaaaacatt tttgagaatt aggtcttcaa 6060 aaaaaggttt aatattgagg tttcaaatta gaaatattaa tatacgggga tttgggttta 6120 aaactgattt ttaaaatctt atttttgaag tttcgctttg atattcgtgc aaaaaaaaaa 6180 ccaacttttt cagacggtgc agctggaatc aactcagttt gtgacgaagc caaggacacc 6240 ggaccgtgca ccaactttgt cacgaaatgg tactacaaca aagccgacgg aacctgcaac 6300 cgattccatt acggtggatg ccaaggaacc aacaatcgat tcgacaacga gcaacagtgc 6360 aaggctgctt gtcaaaatca taaggatgct tgtcaacttc caaaggttca aggaccatgc 6420 tctggaaagc attcctatta ttactacaac actgccagtc atcaatgcga gacgttcact 6480 gcctcggaaa tatggtggct ttcgctacca tactaacaga tcaagcgaga ttgaggagtg 6540 tgcccgagta agttctaagt taatagtgat atatgctttg tttccccttt attctttgac 6600 aattttcaaa tactttttgc ataattacct tatttctatt cccttctgtt tcccattttc 6660 ctccacccgc tacaaattgt ttcccgtact ctctcctttc tcactttecc gtccgaaggg 6720 acacggcaat gctgcctaaa tgaactgcct aataatattt atgaattttc caattttcta 6780 attctctcaa aaaaaaaaca aaaattccct gccgttccgc cactgctttc ttcacccatt 6840 gttgcgctat tttttttaaa taaatgaata aagctgaaat agttaacagt ttctgaaatt 6900 gcatgtaagt ttgtagtgta tcagtgtgtt tgtcgtgaaa gttttttttt acctgcatga 6960 tttcctgaac tgcatgaaac tgttcttatt acgttttaga tttgctgaag tgtgctagaa 7020 gtgtgatttt gtttcagaag acgaccagac tacaacaaca tcacaaccag aagagctccc 7080 aagtttgcca cttgttcaag aagatcctca gccacgaccg gcattttcat tgaagtaagc 7140 caagtgccta acgtgtagtc gaccaaaaaa cttctcgtat tttaatataa ggtttccaag 7200 tattaaggaa tcagtagcat gtaaattgtg tggattgttc tcctgggttg atgggttttt 7260 caatcagata ttctcactca tggagtagct tatatgggaa tttatttgag aaatagaata 7320 tccaaattta tgtcataaca attattaaaa agttgtgaag tttctcstta tgtatataaa 7380 caaataagaa attcgccttt caaaaattaa ctgtatgaaa gagctgastt caatttgaaa 744C ttgagaaaat aactggttca aaacgttgga aaaagaagaa aaatcta? = e gtaaa tctat "75 0 ggactttctt ttcaggtcgg ggaaatttcg acgattttta tattttcaaa aatcattcac 7560 aaatatacac caaaaattat ttttaccata ataaaatacg gaatttcact ggattactgt 7620 agtattcatg taaggttact gtattgttac tctagggata ctacaagaat atttttgcaa 7680 agtatagaga agttgtaaga ttactgtaga ttgaaaatct agacaaaaat cattttccgt 7740 ggggatagaa aataatctgt acaaggctta tgttgaaggc tgggaaaaaa taaagcacca 7800 ttttaacagt gattttttta agcatatcct ctttcccagg aaatccactt ttcaaatata 7860 tcccc = CTAA actctttaag acaatccttc gcccatagtc gtcgccgtga tgctccattt 7920 gcacgttccg tatccgcccg tcaccatact cetgattccg aagaggaacg agttgactgt 7980 tatgctgrtc cagatccagg atcttgcggg taataaatct eacetateca ttacaaccat 8040 atgattcaga taccgtctta gactaccgtc ttgtttggca ctactctgcc acgagtaact 8100 catgccgtca attctactat ggtggatgtg ctgggaatac gaatcgcttc gagacccggg 8160 aacatcgtgt ataaatgtga gttgctaaga ttgaagaacg cgtggaaagt gtgtcagaag 8220 cttcaaaatc tctggaagag gttagactaa cggatccaag gatggattct cactttggat 8280 atcat? = tee agaagttgat caaatcgaag aagaagctga atatgtcatt gttgataccg 8340 gagctctacc tgaattatgc atgcttccag aacaaagagg gtcttgttat gataacattt 8400 tgagatggag gtaagtcaaa tcaagaatag aaaattcgaa aatccgaaaa actttataat 8460 tatactaaaa gcaaaatctt aaaatctttc agattcgact ctgaaaagtc tcaatgtgta 8520 accttcatgt attctggatg taatccaaat gcaaatcact tcactagtca ggttagtttc 8580 attattttgt gtcctttcgt ggaactggcc ccttggtttc taacttgatc ttctccttcc 8640 gaatacccaa tttgagcacc gctggctcac tttttcgacg gtgacgttcc tcaattctag 8700 cggcctctgt attttctgag cactcttgag caacagtttc ctcactgsaa atgtttgttt 3760 ttcaagaggg agtgagagag agaaataaac gtacaatttt tgaagcc ca catgatttgt 8820 tagaagtcga tgccgttctg cagtatcctt catgtttcgt agttgtttct gtagtaattt 8880 ggaactaaga ttatgaatta cactgcggta aatcatcact tgtgcatgca gttgcatttt 8940 aaagcaacaa tcttrccata atgcaacaac tgatagagcc gccacacaaa ttgcaataat 9000 tcgaagtcga tttctaatt ctttctttac tttttgtcta tgctcagctg cttcttcgat 9060 gtgcttcttc ttgctggggt cgagctcgca atgaggaaat ggttcgatga gtggaccgtg 912C ttttttgcat tgttcacaac ggcgtccagt gtatttgtct gggcagtcac acgaaagagt 9180 gcggtttttg aaatctgaaa attttaaatt taagaacagg atctatagca gttttgccca 9240 tcacagtcct atgtctatat taaaaaaaat tatcggacat taaaaaaaat gttttctcat 9300 tttctataaa tttttcagta aactgcattc gsatttaatc ataactttta atcgttaaaa 9360 acttagtctt taagtacctg gggatccgta aacacagaca atttcatcac aataatcgcc 9420 acatcacaga ttcaaatccc tgcatcttcc atttctcaaa cacatttact aacccctcga 9480 tgtatattgg cattcacttc caaaatatga gcccacacat tcacatcggt cccccttcca 9540 ttctcctttg tttccgcact gaaataattc aatagatttt? gaagtttag ggcctcaaaa 9600 atataecttt tccgctggcc gatagtcaca catttcacct ttccatccga cttcgcaaat 9660 ctgaatagaa gcacggctca ggctttccgg gtcgaagcgg aatccgaccg agagtccgtg 9720 aactgtaaat tgaaaatttg taattccaaa aaaaaaacag cttttgcaaa aatcgtccaa 9780 gagttagaca aagaatttta ttatttttct caaaaagttc aaagttgtat cagttttaaa 9840 ataaaatatt taataggatt gtagagcttg ttagaaaaaa taaaagctac ttgaaaaaag 9900 aaagctatcc aaaaaggtat tgagatagtt tcaagcaact ctatttgtaa actgtcgagt 9960 ttctaagttc tacaaatctc ttataacatc gctacatcta ctatcaaact ttqaaaaaaa 10020 ACCAT accac attcaaaatg ttcacattta tctccagtct gtcccttgat acaatgacaa 10090 atccctccag catagattcc tccattacga cattcggctc tcggatcatc cagagcaaca 10140 ttgtctagaa tacttctctt ttgaagaaca cgatgcacgt cgctcaatat attttcatct 10200 agatctagtg agtcatctcg tgattgtgct tttgttgttg ataaaaatag gaagagtaaa 10260 gtaaacagta gtggaaaatt catagcgtta gatactgaca agtctactat caattgattt 10320 atttattgcg tcttgaaagg ggtatcaatg agagaaatag g? agatgggc aaaatgcatt 10380 tataagagaa tacaaaagat gacgtaattg attaatcaga gatcagttga aaatactttt 10440 aagtatcaat tattatctgt gaagacagtc acgtgactct gactcgaact caatttgcat 10500 gttcatagtt ccaatgttaa agaaagtctt tgggttttct ccagatgaaa caaatgattt 10560 tggaatatta aaegtgactc ttctctgaca aggtttgagt ecgtcatrac aatcgtgata 10620 gatattaagt tttggatcaa tagtcatcac ttcggaagtg tgtccggt = a gaaggaattg 10680 accaagagag tctgtagttc cttcggcaag aagatcgtca agatccg? tc ctgaaaaaaa 10740 cttttatttt gaaaaatttc aatgagttgc ttcatgttag aatttggaat ttttaaagat 10800 gttagcaatt ggtatttaaa tgttcaagct aacgtaatta gagttattca aacaagcttt 10860 ata taaaaac tttgtgtaag attcggtcta attagaacat caatttttaa cgcagctgat 10920 aaaaaacttt aatttcaagc ttcacataat tctacttacc ggtatcacca tcgtagagct 10980 tcaccctcgt gttagccagt ggtttgtctc cacacatcag aacaccctca actccagctg 11040 attgggtgaa tacagcttcg gagccaattg cacaaagtat gaaaagtcat gaaatgcacg 11100 cgagtcgtga cattattttt gtctgaaaat acaaacactg actgatctga ccttcatcgg 11160 ttatagcaca agaaactctc gttggttaga aaaagatacg gagaggagaa gtgggaaatc 11220 aacaaaagaa gaattgacca cttgaaatag ctggttttca aagacgatga aagatataca 11280 acagagaaga tcggaagtga gaagaaaatt ttcatctgga gagaggagca acttcttgta 11340 tttcccactt atttatatac ccaa zagaat tcacctgat t ctttccg = tt tgtgtacatt 11400 tcgetgacta acgtgtgctt cttcggtttt gtcatttctt attgttcect gaaaataaac 11460 agaacaaagc aatcataagg tcgaaaatcc catttagaga tcaagag tg tacctttaat 11520 tgtgcggcat ggcatagttt tatcttgctg aactctcacc aattgatgag tatgtcagta 11580 aatggattc catccgatcg ttgctccacg gtgatctctt ccgccgcctt ttcatccacc 11640 atacccgttg tgtatggctg gcaactgtqa acagcgcctc agtggaatgt ttagtttgat 11700 atacagttta aaataatttt ctaaaccaaa gaaatcagtt tttgaaaeea gtcttgtagg 11760 catgtcgggc gcaggcacgc taacgtgaaa aatagaattt cgagtgctta actattttat 11820 aatacaatca ttccaattaa actacacaat gaatgacccg gataaatgaa atacaaatac 11880 aagaatttaa aaaaaacatg gaaatttaaa cttttccatc atctcccttt gctggaatat 11940, Tatatttcat tcgataagct tccaattcgg cttttctctg atcggategt acactgtgtc 12000 tctcatccat ctcttgttga gctgtcattc tcttctcatt ccatttctga gcttttgctt 12060 ttttgtggat tctgctgtat tctttgcact tgcagcagca caggcaatga ataacagsia 1212C gaattacagc aatgattcca gcgcagatgg caataacgat tgcggccgoc gatgtgctca 12180 cccagcagac attgtatttg acatgsttga tattacagtc tggatagc = e cagtcgaatg 12240 gcatacatct tttcgttttt ccaccacacc agaagcaatt ctgaaaaaat gtgtttttga 12300 aattttcaat atgtttgctt ataaaattga atttaatttt tcaaacagcg tttcagaaac 12360 tcaacttctg aaattaggaa agtattctca attgagagct gtttttgcat taaaagtttc 12420 agtttagaac tacaggtgtg aaaaaatctg agcaagtgaa ttgcatcaca caccaacgta 12480 gtttacgcgt caatttattc gagtgttcat tgtagagaaa gttaggtcac cttccagaaa 12540 attaagaaac ttgtttcaga catttttgct cttttagagg aatttttttt tagaggaaac 12600 acgcaagttt ctttgaaaac aaaaacaaaa tatatttttt atccacttac cgagcccttg 12660 ccaacacatg tttcaeaagt gttcaaatcg ttcgatccaa ttctacagca ttcttgtttc 12720 tctgaccatg tcatgttatc cgcacatact gatactagaa caattgagaa aaagag tagt 12780 tcatcgttct aatcggtgaa gaaaaatcaa taaatagtaa caacttgagc aagtctcgta 12840 actgagcgac aaaaccaaag tagtaatgaa atagaaagat agaaaggtaa actcaaaggg 12900 ctcgcgtgtg tttgtctatc gagtgccaat gagttttagg agtagcgaca gaaataagtt 12960 gaacatacga ggcagaagaa actatgtcgg gctacaagat tcttgtgcct actttttgaa 13020 aaagaaaatg catttgagaa aatgcaaatg ttcggcagaa atcgaatgga gtttagagca 13080 aataaaggtg gaatggtaaa gatcagcaaa aatagttgaa gtagatttca caaatatttt 13140 caaaaaaaaa tgaaagataa taaatacaga aaacaatata tgacgtattt ttcaatcatt 13200 gtttttgtat agtgcaaatt cagtagttgt acctgttata agtacagcga agttatacat 13260 tttagagtgg gtcttgtcac gatccatatt ttttgaacgc aatatttgaa atccaaaaaa 13320 aaataaagaa actaggcgcc aagaagctat agtagctata cgcataaatt gtgaatacct 13380 taaattccaa tgaattacat caaaatagga aaatcatata aaaacgaact tagttgtcaa 13440 ttcaaaaacg tttttaaaat tgttcataag cgccgagctg tccccctcag ttttcgttta 13500 ttcagctttt ctctctctct ctattctcta tcgtcaccta tatttcatag tccccttatc 13560 agtgaatgag caaaagtgga gatggaaata tgataccgca tgcttcaaa to aaatttgctt 13620 at acsaacc aacatttgaa aatttccagg aaacttgtga acgagcctgt ggtaaatgga 13680 gaascgtggc agcgtgcgag ttgccggccg aacacggaga ttgccaactt gcgactccca 13 40 ggtatgtact gttgacaeat tttacaaatg ggatgggaag tggtcggcga tcaggcggaa 13800 caaggtttta atgttgatgg aatagatgta gtaactgaaa acaaaatgac agatgtacat 13860 ggattaaaac acataaatta tgcggagtca aaaaatacta ttttctggaa ggtgactaat 13920 attccagaat ttgaaaatgt ttttctctgt ttgaaagtag aacgggacct tttacaaaat 13980 aggctgaggt aggtaggctg tagaaagtgc ctttggtgtc tttgtaattt ttgttttcaa 14040 aaaatcactt gtaagcacat gaaaatcaca tgaataatga tgtaaaattt agaaaattag 14100 tataaagaag atttacattt taataataat aattccagat cccaaaaaca ggtaccatga 14160 tcccaatgtc aaatgatgat tgcggaggaa gtggactgga gttctcttca atggaaacgc 14220 aaagca ^ act gtgaatctct ttgccgagtt gagacattat ggtccaacaa cactgacttc 14280 tgtacattgg aacgatcggc cggtccatgt acagattcta tttcaatgtg gtatttcgat 14340 tcaactcatc tcgattgtaa gccattcact tatggaggtt gccgtggaaa tcagaatcga 14400 ttcgttagca aagagcaatg tcagcagagc tgccgtcctg gagacacaaa atctgaggat 14460 atctgcacac tccgcccaga gccgggaccg tgtcggctgg gactcgagaa acacttttac 14520 gacccggtga tccaatcctg tcatatgttc cattatggag gttgtgaggg aaatgcaaac 14580 caga'gttgga cggttcgatt ctgcttccga cgatgctcga gtgtcaaggt tgaagcaagt 14640 gagtgggaca gaaagcgaga gctgacgtct gcatccacgc cagttattta tattgttaac 14700 aaaacagcga tttttgttgg aaatactgta agttattaat tttaattcga agatttctta 14760 atatttaaac tggccccatg agagtttggt tcattttccg acaatagact gcaaaattga 14820 taacttttca tgaacacttt agccgatttt agctagtttt gtttsttaaa atttggtaat 14880 tcaaaataaa aaccttacgc cactccactt ttgaatactt gtcaaataca ttttttcagt 14940 tccgeatccg atgcaacagt tacggagtgc ttccaataac atggtacaag aacggaggtc 15000 cggctcgcga ccctccagtt agaatgatga atcactgaag cactttggaa attgtggatg 15060 ctttaactgc tgacgccggt gtctacactt gcattgccgg ccaggatagt acaatgagcg 15120 ag sagtcga ggttgtgatc aagagacttc ctggtcacag aactacatct cgtccaatgc 15180 tgacaecatc caagaacttc tccttgggaa ccccaccgac accacctt to tctacagttt 15240 ctacaacacc cttccgaatc tatacgcctg g atctgctcc atctgatcrt cgtgtaagcc 15300 gcccgacaag caattcctgt atggatgtgg gtaasgcgag cacgtgcs-at ttgatcgtga 15360 agaacggttt gtgcgggaag aagcgatatg gaacattctg ctgtcacact tgcacccggg 15420 taaattttaa ttcataattt gtttggattt tttgatttca aattttcatt aatcttttaa 15480 tgttttctcc ttcataatat ctccattgcg agatctcttt ttcccttctc ttcctatact 15540 ttcccctcag acaattggct aattactcgt tcgttccagt aaataaatat gaatttattt 15600 tactttggta cttcttccta tacataatca tggcatgaaa tacaagacaa aaaaaacaag 15660 aaaaaacaat ccacttgaaa tccattcagg tgtgaactaa catcttactc tattaacttc 15720 gtgccattac ttccacttat tttgcctatt cactaatgaa gtctctgaga attattttct 15780 gtctaactct gctgattgca agcttcccag ctcagcggag ccgccgaaaa cagaaatttg 15840 tacgccttcc tagtgggttc acgtttcctg cggatgcggc gagtaatttt caaagagatg 15900 cgtatattcc agcgacggta aattttcgct ttttgttaaa tgaatttcag gcttcaaatt 15960 attttctagg acaaaaattt aaagtaggct tgcgcatact catttccctg ccttacctgc 16020 caacaggcta gcttttggag agaaatcaaa agtttggtgt ctgtaaatct aagctttccg 16080 aa aagtttttgg cgtccga gaatccgcta ta cactttaa gattgataaa tatttgaatc 16140 aggtttattt tgcactatta aggcgtgtag gcactaggcc ggcaaagctc gcctacgggg 16200 tcaagtatta agcettacaa ttcatgaagg tcttgatttg gttacagaat tccatctaaa 16260 caaaaacatg attacttata gtttgccccg aaaaatttca agattcttca ccatctgaga 16320 cgctatttaa agctccacca ctggagaaca caatccagct tatggtaggc ccaatttttt 16380 ctaaatttaa atctsattct cttcaagctc acaataccga tgtgcaagga atgaactacg 16440 ctgagtacaa gcaagcgatg gccccacaac cacatccagt cgatgcttat tctccaccac 16500 aatggtccca ctcctgcacc ccggttactg tagttgaacc acctgcaatg ccgtatgaaa 16560 tgactacgat tgcatctgtt ggaccactta ctactcccgc atcagtcggc tcgaagaagg 16620 gaaagtttgt gattttagtt aattgatctt tcaagtaatt ggatacaatt tccagcatcg 16680 g ^ gaattgc tcaaaacttg aacgacaggt acaccagctt aacaccagaa gctcaacgtg 16740 ctcagaaagg tcatacctat acggctctgg geggtggaca attctatcaa agtttacttg 16S00 gagggg aag atgcaaggtt agaacttaca aacteaatt c att tt EAGA aaggaggccc 16S6C cggaggattc tscccactct cgttctttct aaacggcggt ctaggaggta ctggtggtgg 16920 tggtaacaat ggattcttcg tt ccggtgcc tgtagtcatt ccgcctccac cgccaccgcc 16980 aactgtttca accaggacca cgaacccgtc gggattcctt tgctgtaacg tgacacttga 17040 gaaaactatg gaagacgcgt acctggccgc aaaagcagat ggtgcsecac tgtgcaatgt 17100 acagaaaatg gcaactgcag tgcaagcggt ggggtttatg gatttcattt tataatgtaa 17160 tgtgctcttc cctagaattg aataagctta caacttgaat tacgacctga attacaactt 17220 aaaatatcca gaacaagctt ccaaatttca gcaagccgaa aaaaaattcg gaacaacttt 17280 cgaatcagtc gctgctcatt cggacttcgt cgcaaaaatt aattttgccg gtgacctgaa 17340 ctgtaaaata gaaatcgatg ggaaattcat actagcgtac gcaactccaa tcgccgagca 17400 agaggcgaac attgtcgatg ctagctcatt cttctcggga gctgctgata aggatttgga 17460 tggtgtcaat ggtaccaagc ccacctacat tgtctacggt cccattaaat aatggagggt 17520 ctagctttaa agatttctgt atattsaagc tgaaatgtga attaattgtt tatttgccaa 17580 gttggaaata tcacaataaa tcatttgaat agttcgaaag ttttcaatcg gaatgggaga 17640 aaattcgaaa atttaggig? aggtgaaaag ttgatgaagt aacacaatta actgtgctcg 17700 aat ^ ctgaat agaaggagaa aagascctat aaacagattt tcaat taca catattacac 17760 gaagaagaca aacaattcag gtagttgcaa aagaaaatac gtagaaaaaa gagtgsagg »17820 ctggcgggat gtcagtttgg atgtacaaat agaactcctg aagescaaga aacagaagaa 17BB0 tc? acc? atg atcgaacctg aa tggattt attgttgatt aagcaattct 17940 gaatctctac ctcgtttgat tgtgtgtaat gcaagaar.ct aaactcgtga gtgtgattgt 18000 taetgatccg gaaatgttcg gctgcttgca tatcogatta geatratcaa cgcccacaaa 18060 tcctgttctg ggtctttttg aggtagtcat taaaagctgc cggattaagc gtctcaattg 18120 cgctcattcc ctgcttatcc atattggtta tctgctcata aatcggaata gaactatgac 18180 gatcgtacgg agaaaagctg aagcgttctc cccaatggca aaagtccgaa gagatcacaa 18240 acaagtttct tggatcctcc stgtaatgag caaaaatatt tccat = CGTTs tgctgcctag 18300 agatccaaca atcccggtaa agtaccggaa caatggt? ta acgtttcraa cccataacct 18360 ttgcaataaa tgggagttgc atttcaatac tatgctctga ttcttcatct cggcgat ca 18420 tcaaatcgaa atgacgagtg gcacgaagct cctcgttaac tgcaaajjgc aatgttgtaa 18480 aagatgtact aagagtgcaß tagattactt ttgtgatcaa cgatcaagtc gccgagtgga 18540 gttctgtact tgctgcatgt ggttatagca catccattta gagcaacsac gtgagatggg 18600 ccaagaatga agactctttc actgaaagtt attgagtaag ccstgtcgcc aagtacaaat 18660 ttcaacaact cacactgctg atgaaacaac ttgtttgaaa gcatatgcag ctgtttctcc 18720 acsatacgaa tatcccgcat gtctgaaagt tatcagaaaa taaatattaa atgcatttag 18780 agtattacgg tgaaatcaac gctcgagccg ttccaatccg tggaccsgcg ttgtcaagcc 18840 attttgtgag ttgccgatca agatctcgct ggttggcgtt gtaccatgat ccggcatgtg 18900 aggcagatct cgtgtgctcg ccgaatccgt ttagtgacat tttaaaztca gatggtctga 18960 atattaaagt tttgataaat tgttgtatac gacttgatta atatgtctag tagggttttc 19020 tgtttcccaa aactactgtg atagtcaaca ttgaaaaatg gaaaagtttg aatttaaata 19080 ttcaaataat tttaattaat attcacaata taatattaaa tcacacttaa cagtgtaaca 19140 ttcaagatgt tctaaaaata tgagccatcg ggctagctct acttcecgaa ttcgaatcaa 19200 ctggctcgaa gtccggggaa agaaaataaa tttttaatct ggtttacgtc egaaatagaa 19260 atggg? atc ggtttttcat tctgaataat ttccgagaaa cactt = ataaaattca CAAA 19320 gacatcttgc aaaaggaagg ccaaatgtcc tgagaaatag agcacoagag tttt? AAATA 19380 cctgcaacaa caggatttgc ttctattttg ttttttgaac tgaattttaa actattatct 19440 attctgaaaa catt ttttgt tcaagaacaa ccaaaaaaaa tttacagcaa aatgtggcaa 19500 tccgaaaatg ttgatgcaac aaaaaagtgt tttttttttc attgaatttc agttttgaaa 29560 actgatttct ttccaaaaaa aaaattttga aaaßcgaagg gaaaaaagtg aaaatccaaa 19620 aatgctgatt ttggtttttt tttcaaaaaa aaagcatttt GCAs = gtgtg tgcttttttt 19680 cgaaagtttc agaaccttga gacaaaaaac caaaattgtg ttcccgagtg aagcccgcca 19740 cgtggacatg gtcagacgaa tcttgttcgt gttcgcagcc aattttcatt tttgctgaac 19800 gcataattgt tcaaagaaga ttcggtctaa aaagacgaaa ttgaaataga ttgtg AATC 19860 ctttgaaatt ttcttttgac aaaaggtcac cgttatccaa aaattcsgat ggtctcgtga 19920 ctaa & Attaa aeaatcaaga taatcatgat tgtgggectg tttta = aata cacttttcaa 199S0 aaacgaaatg taggctccaa tccaaactgc gcatcaagac caagaarata asacttttaa 20040 cgtagagaaa actcgggaga ctttgaatat taaacatcgc cgtcasgttt ccgtcagagc 20100 gcgcctgaaa ttttctagag gcttctttca aaaagctacc catacaaata atcataagaa 20160 aaactttgca aaacgtttta ttccacccaa aaatgtctga aattacccgt aaaaagaatg 20320 gtgatttgag tgtgsaggga ggttctgtca aacagtttga ctgtttcgcg ttcgacgtgt 20280 ctcgacgtgg atggtattga agaggaccgc gctgatcttg tgctggccgt cgtcgtcttg 20340 tcgsaccgcc gcgagtagtc ttcagtctac caattacctg aaaatctgac actttttgtg 20400 ggctgcctga atgtgasact agcaatgcca tataataatc ataataataa taatgaagag 20460 ggatga gat gcatgccaaa agaatgaaag gaaagacgct cttctacaac accagccgat 20520 agaaaaagaa agtstttaga gactaaaaag agagtattgg gtgatgggag aaagaacaca 20580 ataggggagg cagtgaaata gaacgagaac aatggaatcg gcagaeattt gacactagag 20640 gcgccactgt ttcagtcttt ttcgcacttg aata tggaa gagggccaag aaggggagtt 20700 ccságaatgg aaaaagtggt aggtttgtag aaaatctgcc ttttcttttt taaaatttcg 2 0760 tgt CACTAC tttatttcgt gttcactcg ttatgtcttc catta AGGC aggcaaagtt 20820 tcatgcctac atacctgcct catgcctatt tgactttcaa tataaaactt gatttttggc 20880 attcttcatt ttataacaat tgtaactaat aataagcttt gcaaagtttt ctgaaagaaa 20940 tt? Tctaaat tttcctggta cactgaacat ttttcggtat aaa = tctatg cgtatcaagc 21000 ctstttctaa gagccgtaag taítttcagc tgaaaatgta aactacggag tcaatattta 21060 cttcgtatca tccatcttcc attccgtctt gtttacacct acgceaggta tttagacacg 21120 aatgattgtt tttctcgttg cctaatactt tttcccccga aat = ttccca tattccagtt 21180 ctgaacaatg cacttttcag cggtcatcgg gtccatccag ccetrattca gccctttcat 21240 ttatcttcgt ttctactttt agacgaaaat gcaaaaaaaa gac = aaaaga cactctcttt 21300 tgacgctcac attcgctcac actgctgtgg tagaaaaaca ctcactcggt ggctgctggg 21360 aagggaaaac gagaaaatgt ttggtcacgc aatacgccta tatttttgat ttgactttga 21420 = tctttatac atttttcacg gggttcaaaa acaattatga agaaaarcg-t c ~ qat taa .at 2148G tagaatgtag attctttata ttctcaatca aaaattaatt ttggaa === c aactatccaa 215í0 aaaacgaaaa aagtaataaa tgagtacttg aaagtgaaat ggggcaatta aacaagataa 21600 aaaagactaa aacgtgagac atctcacaac gggtcacggg caagaagtac acgagaaatc 21660 gaacgtgagt ggggaggcag agacactcag ctgactgcct ggcctgacgc tcgctcacaa 21720 aacgctctca ctctettcct cgctttgccc gctctccgcc ccgggtcgtc agttcggtcg 21780 atccatgttt gttcattttt ataggtgaaa atttatgtaa gggaacggaa aatgtaaagt 21840 aaatagaaaa gatcgtggga acaattacat tgtaactttt ctggacc = ag ttgtacccag 21900 atgcaatatg tatatttttc tcagaaaata ctgtgttggg tttcgacagg atcgatttat 21960 caaaagcaaa cgagtgtgcg tctcaacgag cactaaagtt cccaact? ga gcatccttgt 22020 ctacatagaa tgtggtagaa atttttaatt ttgatttcaa tagcttttct cttgttttct 22080 tgaaaaactt caaaatttat atttactata aaacgaccaa cgacggatct ggaaactaca 22140 gtactcctta atgcaaaagg caacgaaaaa tcagccagtg acttattz tz tgttctggat 22200 aaaaatcggg aatatttgca ttttgaattc gcactgtatc gataaacaaa acaccgaaga 22260 atgacta tcacgccaaa tg taactaacag gtacgagaaa gggacgcctg ttctacaaaa 22320 ataattcaac aaattttccc caaaaaaatg tgaagtccgc aattct gttttacgta gta 22380 aatcaaaccg agcatgacac tctgacacr.a cgtgcgcctg aagatgcacc tgcctaccat 22440 gsatgcttta catttgctag ttccacgaca tcagcttcca ccccatccct agatgaagga 22500 aattcgaaaa cttcggagaa aatattgaga aaaataaccc aaaacattct gaaacattgc 22560 ggaaaaaagt tagaaattat gtcgaatata tctgaaccaa tcaacaactt caaataaaat 22620 acaaaaaaaa attggaagac cttaaatagt ctccgcccat attttggctt caaatgaccg 22680 tacctcggaa tatggccgat ggccgtggca agacctccaa tcgtactttt gagcggtcag 22740 taagtgaaga ttaaaatagg aacagtaccg taagatcagc CCAGG? CGA gtgggata 22800 aaataatcga gaggaactga agaagcatga taactaagcc acgtggccac gttcgttttt 22860 tagatcgcca gcsatgttaa cttcgtccat tgtcgttttg tttgtactaa gtctccttag 22920 traattctctc gaaggcgggc cattgctatt agtaaaataa gctacc att ttacctttca 229B0 ATAC? ttcat ccactgatgg ttttcctatc aggtgatcat ttttctgccc ttctcaatta 23C40 cactatctaa aaatgatgaa gtttttgctt cgcggctatt tggttgaagt gatg = Tatat 23100 ccattgattg tcgtctccac ttgtgctctt tttacgtctt acaacttctt tttaagtgtt 23160 ttgcgtattc actgtttcat ttattttttg cagaaaatga gcctgttcag eaaatttttc 23220 ggasgcatga tgcaagaagc tccgattact cc acaagaat ctattcaaaa acttcgggaa 23280 ttcttgagaa acagaagata gaaacaagaa ttcttggaga aaaaaattga cgacgtaagt 23340 tggaagatca gttttggtcg aattaatcac attaaaaagt gctgaaatcg aaatttttaa aetctc agt 23400 ctcaagtgac tgtgacgtaa .ttaaaacatt gctcagcatt tacattgttt 23450 tttcgaagtt actgacgtct aatccaaaaa tagtcgagca agagcaataa aaatttctgc 23520 tacgatacgt ttgggaaatt ggaatcatag ttttttaaac tccatttttc aaaaaataca 23580 atcagtaagt ttattagaaa ttcggaaatc atttgagaaa cgtttcagga aagcaaaatg 23640 ccgtgaagta "tggaacaaaa aacaagcgga tggctctcca gtgtttgagt aggaagaaag 23700 eettcgagaa? cagttgatc catattgacg gagttttggc tactctcgaa catcaggttg 23760 atattagaga gtatataaaa aataaattga ataacacggt ttttcttcca gagagaaacc 23820 ctcgaaaatg cttcaacgaa tgctgaagtt ctcacggtta tgaaacttgc tagcgatgcg 23880 ttgaaagcgg ttcataataa catggatagc gaccaagtt gtgatatgat ggataacata 23940 gatgaacaac gagaagtggc gaaggaaatc gcggatgcta tttcaaaccc tggctttaac 2400C aacgcaattg acgaggccga tttgctgcgc gagttggtgg atcttgaaca ggttcgtcta 24060 taccaccaac atcgtgtaat tattagaaaa ta taccagga agcacttgac aaagatttgc 24120 ttgatgcgag agctccccca gtcacgcttc cggatactcc caatattgca cttccagcct 24180 ccagaccgag agctaaagaa gctgacaagg atctagaaga cctcgaaagt tgggcaaact 24240 aacttctcta agtcactttc atatttaatt ttcggctatt ttcgtttcat ttgcatcccc 24300 ttcatcaatc ctaccattct ccggagattc tcctaaatca actttctaat tacgacaaat 24360 tcaaatagtt gaatgatttc tttcattcga tgtttagcca aacaaatttc cccaaggcta 24420 egatcaacac tcatcaaaat tgtaacatat tatcgagctt tttggaaatt tgtcatttta 24480 tacatcttgg tccctttctc coagcatgca caaaatctto ttaaagttcc aacttttatt 24540 aaaaattcat tetggcaaac atgttatttg taccggttga aaacgaa? = t caagcgagaa 24600 acagccacat ctcagatctc cctaacgatg gctcaacccc tttqscg-cc ecct ctast 24660 gtttacactt ttgctcattt actaatgaat ggctcattta ctaacttgct gagatttttt 24720 aatttactac tgctaattgt aagatatata tcatttatca tttactat3t ataaagcgct 24730 ta-tccgttt gtccatagtt tgtagtctat gtagtctttg tagtctgtga cgttttggct 24840 tctggaagga tagtgagttg ggcttagtgt agggatatag ggggtactgt agtggtacaa 24900 tagt gtaeg gtaggagtac tgta tgatta cggtagtttc agaaaaatta gtttteagct 24960 ccagaagtcg ggggccgcgc cggaggtgcg gtccacggct ggttttacat aaggtagttc 25020 cctacttcca caaaaaatgt attactcata actcagttag cgcgctatag ctatagcgtt 25080 tgagtttaaa aaaattgtgg ccaactgaaa tgctgtttgt cagagatgcg agctctaaaa 25140 catgatcgaa atattctatt tctgcggatc tagaatattt cgatcat tt ttggjgctga 25200 catetccgca atcgctaaag ataactaaaa ggtaccaatt aacaaaatgt gttttacaat 25260 attgccaaca acattttagg tttctttcgc tgattgtttc cttttggttt tggtgatggt 25,320 cc jgagtgg tttttttcgc tggttctact attttttgga tcggcaggct c gaacaatt 25380 tcttcttcaa ggttgtacaa cttcatcaaa ccatccagag tratgtcgte gcttctgctg 25440 tccsacatat tcatqcattt gacggaactc ttcaactttc tgeat OEWG ctggattctt 25500 !: ectatttfca ccttttcgat ctatcataaa gaaaacttta tatcatgtta caatagtatt 25560 casatcagtt tggaatgatc tcctccattc aaaattctta atgatcagcc gatccactct tag = 25620 gccacg aaaaatgtgg gacaattgtc tgagaagtga aaaatagtts ttaatgttcc 25680 acatataagt asccagttgt aatacatgaa aatacstctt aaaa = tacag ccact ctag 25740 gtittattgc ttaaa attgt gttccaatct gccagtacta TGAC gtaat tcgttgatcc 25800 aatcttcgaa tagccjtgag cacaggcttc gccggcactg cacacsaact tcacg.ittcc 2S860 ac = tttgca gaggtagagg acgaacgact ttcctgtaat tggr saata ttgttttaaq 25920 acaaagtcag taggaacgat cgtactgttt ttagaacgag actctctagc tggtggccgc 25980 atcgagcatt gatggcatcc aagaccttga acttctccgc tgaacgatat acgar.gcttg 26040 aatatggatc cactgaaaat tgaggttatd gtagattatt ggg = - tatt atgattccac 2C1C0 coat? AAGAA ctgcgteagt aactcgtttc agattctcgc tatcctcccc accgctttet 261C0 cgttgtaatt ctatgagaaa acggtagaat ttggtgacat ttgtcga tt aaacaattcc 26220 caaacatctg acgaggcaga aaatttgcgt tttttccasa aatgcazaaa ctttcaacaa 26280 ttctagggca aacaaaccgc acatcagcta aactgtgatc atgctcgtat tcggcgttta 26340 gcgagaagca taaatggtag aataaatgaa agatatcggt aggttcgcgg gaatccggat 26400 tgtagtcttt gagataatca acgcaatttt gtttcagatt cgtcatcagg tatttgtcgc 26460 atagcctgag aactgtgcac acgttttgtt ctgaaaataa atttggcatt cattgaaact 26520 acatcgatca tgaactacca tcaataacat ccggatataa accaagagaa ttgggagaaa 26580 tgacag tgat caacttgaga atatcttccg gtgactcatc aagsatattc acttta 26640 tggcgccttc aaggaaaaac ttgttctcca tcaagatgcg gaaataatcc gaatttcttg 26700 tggatccaca caaaga.tgc aagtactttt gattaccaac aataataggc cagtttcgaa 26760 cgactcaaaa gt agaaaaatcg tcgacctgaa atttaaaaaa aaaaattcca 26820 cgtaatcgga cgttcgttta tccttctagg aaggtttcat gacttgttgt cggccgcatt 26880 agaatgacgt ttacggggaa atcattattt attccgaaac gtgggc ttgttctgtt 26940 taaatt ttgaaaggtt ctccgaatat taagcgaaaa aaacttarat taataatata 27000 aggtctC3ta gcgccgagta aacaat taatatttga ttacaagttt ggaaagatct 27060 ctctga gatcaggaag aaaaacttct tgaaacttta gaagatgaaa tgtgtc 27120 cgtataaaet ttaaaggtgc atgaataaat ttctcctttt ggtcctgcga cgattaaact 27180 ttttaatcaa ttctctgggc tagtttttat tcaataacta gaaar TTGT ttatttttgt 27240 Cccctactta aatcatatgt tattttcttc etcctttgeg tctt = caggc tttttta27300 gaagaaatag caattttccg ataaaatttg tttatg ttaaaggcgc atgcatttat 27360 ttqagagacg gqr.ctcgcaa cfftgcíeact cctcggcccg atttgttctt cgtttgcgcg 27420 cttctcaggc ctttaaaaga tagttccgtc gtttttttct caatttctgc tgaaataagg 27480 tttattttca tttaattaaa aaatcttggt aaacatttaa actcatatat tcagaatttt 27540 cattcctctt tcacccagaa aaccgaattt caatattaag ateaagaaca catctagaac 21600 atgcaaaaaa cacaattatctctctac tttcatttta ag? rtgattt tttgaagaaa 27660 AATCs = t? aaa tacgtccatt attgttgcat cccttgtttg catccaaagt tgactcgatt 27720 gatctcctaa atgtggtatt ccgttcgaaa ttcgattgat ttttac = sgt táacacattc 27730 ggaatgatga taattcgtat caaaccaaaa ttgtcttctt ttcgcctttt ttgtgcagtg 27840 tcagcattaa acaaaacgag aatattgaaa gttacgtggc gtttgcatct ctcaccacga 27900 tgacatcacg aaatgcagac gacaaagaec ggtgaaaaat atggtgaaaa agtgca 21960 taacgtgtta cttgcgaaga cgggttgaga gagaaaacat tccgcsagac aatttg 28020 gtgagaggcg cagatggttc agagaacact agagaaaacc gcgcctctgt ccacag 28080 caagcctctt ccagccccat cgggcatcga cgcatagaca cacatcattt tgccccaatt 28140 tcctttcatt ccgtcaagta tttcgcaact aatcgttatt attaca atacacattt 28200 tacagaagtt cctcttcttc tacttggtcc ga-ccqcatca gataactggg agatcca gtt 28260 gtgcatgttc ttgtgcccac acaaactcgc gcccatttac aattttatga tcgacaaccc 28320 tcaagaaggt aagcatttaa acgtgttggc cgtgcgtctc aaaaaattgt taaaaaacct 28380 ggcgacacgc gtttttccac aatttcattc cctagggcat tttgtatttg aagtaattct 28440 cgcaatcgga attacgcgta cgaatcctgc to getg gtagecaatt ttatcaagtc 28500 gactgcctct tattct gaaaaaagag aatgacagtt ttcagt agtactaaag 28560 tctttggcaa cgatctttta aaccttgata taagcatcat caca Kattath catgcagatt 28620 gatttagagt taagcatgaa atgtgcaagg ctaaaataaa ttacaaaata agtccataqt 28680 ccattttagt aacagtatac atcaat agaatcacat gcgeaatgac aggtctaaaa 2S740 cattatcaaa caaaagacat tacaaaaaca agaaaaatac aatacaatag aacgactatt 28800 tgaaatgagc gtagttaaat tcggaacttc aatagattat cat = gctttaaaaaaa 28860 tg gtgttcc ctttcctccg cgtttgcccg ctacaaaccg gtgattcgga aggcataatc 28920 aaaagtatca gggttgaaaa aacactgatg ctgtcttttt tagggaggtt gescagaaag 28980 agaaagaaac tgaagatttg cgaatcgata gcgtcgtcat ctctcgacgc cagtgaagtc 29040 aagatcggtt acaatagtgt atgcsattcc caaaatccac atat aaccg gactcgtgat 29100 attratcatt tgtaagtact aacaagagat gtgaacgtat ttatactcaa cattagcaaa 29160 ttccagaaga agatctaaac aaaaactatc gaaatg tcaicgtgaa ccgeec 29220 atccat tctacc caagatgccc aatcag aggcaaagga caaaagtcca 292S0 aacggaatca aaacggtcat ttccaacatg tctgagatcg cgaaagccct cgagcgtccg 2S340 ccgatgtgta tgtttatcgc cagttg gccattggac scaaaaataa ccattgtttt 29400 tcagacccca cgaagtactt tgtgag ctcggg aaaegaactt cgatgccaag 29460 acattgtcaa aaeaagcgtt cggcgagcat gatgccaaca acaaga tattttagat 29520 aaaagtttgt ggtttcatta tcatgtgaaa tgcaaa tcagttggta acccggaaac 29580 gaattaataa cgagatcatt tctgtctaat tttattattt cagtttgtcc gtaaaaataa 29640 catcaagagc aagtgcaagg catgtggatg ttcgttcgac attgatctca aacataa29700 atcatgaaga gtctacattc atcctccaaa gatttttgta gattgatgtc agtatcgttt 29760 tt aczaaca ttcgattgaa attctgccaa cttatgcaaa aaattctatt tgcattttaa 29820 atcctttcaa ttcgattttc cgtgtc cagtgcatac aaacat atttttggtt 29880 gccgaacaaa tccagccaaa agaatggaaa gaagacatcg gg tacg ccgccgccgc 29940 cgtggctgcc gacataatcc acaacagcga caaaggcagt tcgaatgatg acgacgacga 30000 cgattgggaa cctgaaccag tcgagccgaa tggcatgctg tcggcgggaa tgggcaagct cg 30060 gccggac aaggatcttg agaagagcga agaacagcgt ctcgacatgc ttcacacatt 30120 cttettgaaa gccaaggaag aaggtaagaa ttctgagcat tgataaaaag tattctcgtt 30180 gaatttctga atttcagata tgccaaggga tacgtgacga caaactgctc agctgagaga 30240 cttgagctga agcaaaaagc atctctcctt ctcgcgaacg tgagaaagta tttttcctga 30300 atcactgaca .aacaaatcag caaacaccgc aatcttctgc ttcgcttcac gttgaatgac 30360 ea aaagctc aaagatacct gttgggagga gttgagcaag taattcacaa acatgaagcg 30420 gaacttctgt ctaaatcagc tcacatcatt aagtcattgt tgtctgcgaa atgatgaaga 30480 aggattcgc ttatttcatg gggagagaag gttagtacca aatggagctt tgtttcgaat 30540 taaagtttat atttacagcc gtcgagtaag tatgtctcca aatcttttgc caagaagatt 30600 attgagaact ctcaaccagt gctcaactgg ctgaaagaag cggaagaaga aaccgaagaa 30660 gagtccgacg atgagattgc gctaagaaat atcagatttg tttttttttt ttcaatggtt 30720 gcttttcagt tcggaggaga cgtcaaggag agtgaattcc ttc gtcaaca gaaggagaag 30780 aagctcagca gctcttagag aaggctacaa aaaatcagce acggcaacgc tgctgctgca 39340 gagcaa aka atgatgaaga attgatgaca ggacttggat tttaattgca Cagat GCTTT 30900 ttt = aaattt acctgggcta cttatgtttt fctgtgtattt cttcccatat tcgaaecaat 30960 tcaactaatt tcgaagaagc ctcagttttt ttttgctttc tccccctttc aatagtaagc 31020 atcatttcat ttctgtcttc tgtcttttct gttcctacgc tgttttccct tcaccaaatc 31080 caat cattt attcgtaaag tcattactat ttgttgttaa tcgtaaacat ttgggaatat 31140 tcttgttcaa tattacaaaa ttcagtctta acacaatgtt caaaaaaaaa gaatcacttc 31200 agatgggaac ccgtcgaatt cggcggtccg atggagaata cacat tqttt tttcggaaag 31260 ttagcccatt ttcaaatcat cacccagctg atttcatttg cgacgaagcg ataaattgta 31320 aagagccgaa sacctt TTGC tgctcggaac agtactatat gtacaataag gettcaetat 31380 tgatggattc aaaactgatg gcagcgattó tagaagcaac ttgtccgaaa acaatgaaga 31440 csatgtgttc taaatggtcg ttgaaaggat ggaaggattc ggt taagtt ttaaatcagt 31500 ttgataataa aatatgtttt tctttt & cag atgggatgag aacaaagaag aagegatgag 31560 aataggatgc ttggcaaaat tccgtgcttc tcgccatctt cgttatgctc tttt tctcac 31620 aactggtagc aaactagtcg aatgtagtcc gttcgataaa atatggggaa tcggt r.agtt 31680 tccaacggat cgtcttattc ttccatcgcc catcacaatg caatcagaat. cttcaaactg 31740 gaastgtttt gaaatcattg aaatcatctt tgagctgata tggtgacgga agaaaaggac 31800 gtetgaaaat ggctgaatta ttataggaaa agatatgcaa gccgcacaat gggctccatt 31860 gag tctggc aagaatctgc tgggaaagat tttggatgga atccgagagg aattgtggga 31920 t;? attcaaat tacaagttag ctccggaatc agaaaattat tattatataa aattactatt 31980 ACGA tcagagatga jaagaa gtggagaaac gaatggaaac tgaa = Gagat tatctattca 32040 ctataga cc gcacatggac ttgatgtaca aagaaagagc AACA aaaaga gtattgtaag 32100 to tcagaaaa tctgcgtaat tgtcgacaga aataacgtat tccagac tgt tcgaagaaga 32Z 60 ett ttaact gatgatagat cctacatcac accagatatt cagaggctcc ttcccgactg 32220 cgcttggccg ccgatcctcg tgaaaaacga gcctattcaa ccat gctgc ct gtaataat 32280 ecatttccet aggtacttgc cttgatcttt aatttatcag aat taacttt caaattccag 32340 atcazctcca cttcgagcag ctgaaatatc acgtaggaag agcacate c actegaeaag 32400 cttgagcaaa aggcggtacc tcaggagcag atcgagaagt ctgtccaaaa gcecgcctcg 32460 aagacgctcc agacatcttt cccgaagtgg atcccgtaca ccagctcaac ggcattccag 32520 aagatccgaa agtacatctc gaagacgttc cggacgg cac tctagaagtc gatccagaag 32580 cccaccacga aaacgtccgg tacgccgatc tccaggagca aagaagcaga ggacaccaaa 32640 ccgaaattgg acaagagcac ggagcagaac aagaagtcag gctaaaagta gcagcacttt 32700 aacctggcca ctgagcccat cgagaagcag aagtaacagt aatgaaagga atttgaaaga 32760 cggaaaaaga gaagaaagac aaaaatctga gaagaaacgg aagcatcatt ctaaatccag 32820 aaaacaccgt tctaaaagat ccgaatcca? agaagaacgt cacagaagac ggaaggagaa 32880 gaaaegagag aaaaagaaga aacgacgtcg gagaagttcc actacttcag attaaacttt 32940 aaa attttt actagtcata actttaaaag ccataacttt tttaaaa tc ataacactgg 33000 tttaatatca aatgtctttt caaatattct ctatttattt attaaactga attcttcgta 33060 gattaagtac tgggtatatc attaataaaa ttacgatact ttgccgaata aatcagttat 33120 aattacaatc tgtctgctgg tgaaaattgt acatgctatt ttcttgttcc tcattctttt 33180 tccattctct gtaaggtttt gttcgttttt tggaaaattc tgagagtagc cggaaaaaaa 33240 aaaaeaaaaa actaaatacc tacagtaatg ccagaggcat attatcaaaa atgctcaata 33300 att = cttttc cccatcccca cgcggcgaga caaaagtatg actcccttga aagtcgtaaa 33360 t? ac atttc ttgaaacaag aacatttgta tattaacgaa acacaaaatt ccgagaatgc 33420 gtsttaagca gcacatttgc cgagccaaat atctcgtagc ttaattctta gaaaaccaca 33480 aaaacactac tgtagcgctt gtgtcgattt acgggctctt tgaattatca ctgatttatc 33540 gatagaatat ttaaaaaata aattcatttc gaaattagag cccataaatc gacacaaaca 33600 ctacagtagc catttaaaga atcactgtag ttttcgctat gagatatttt gcgcatcaaa 33660 tatgttgegc aatacgcatt ctc agaattg tgtcttccgt aataatagac agtggcttcg 33720 ctsaaaacta agaacaaagt aaattaaagt ttttttctgt tcactccaaa ttttacacga 33780 aagttcaaaa tcttgaagca gagcatgaat caattggaaa gtgttcaacg caccctacag 33840 = tgatttc ggggcagtgt at aaactacagg gcacagacat aaaaatttaa attgttgaag 33900 actasaacac aaacatatga attcaagggt cataataaat gtattttttt aaataatatt 33960 tatt_¿satgt atgcatacaa ttaaatacaa cataattatc aaatace = at ateataatt? 3402C caacctgtcg gacaacaact tcgctgaggt gtcgtgtgac agtcaga = ec ct tgtcacac 3408Q cagctgaccg gctcagagac gatacatcgg aagttgagat gagtgactgg tggacattgc 34140 cgacgcgttg gagcacaaca ctcacgatat egagtcatgt cgatgcagcg ctgaaactca 34200 ggaaactatg tggaacttag gtggatcacc caaccagctg cccttcaccg cactgataat 34260 gtacatgtaa ttggagtgca tgggcagagc attgctgcat ttgcatcaca atcaatgaat 34320 ttgcaaaggg cctggagatt ggcttggctg aaagagttga tattatttct attgatataa 34380 taccctaaat ttacgaaaat tatgctaaat taggatttta gttataaece tcgtcacatc 34440 aaacttaa.aa tgatctctga atatcctttt tggtagtgtg gcacca att cgtgctgtaa 34500 cagacaccaa aaacactact ttttcgacat ttcctctcct tg agcgaaa aataaaattt 34560 tttcaaaatc tgtgttttct catacccgga aaaaaccaac aaaaacggcc ttgttccaaa 34620 ggcggtgagt atttctattt tatgaaagtg gccgagattt ctctttttct acgccaagta 34680 gttaactctt cgcggcaaga cccaccaatt ttctaacctc taatct ttt ttcaacarga 34740 atatecaegt catcatagaa tttgcactcg ggettataga tttggagcct ttgaaagtat 34800 atgeaccagt ctatatgggt gttgggaaac gaataggcag tagtctrctg gaccaattgt 34860 agsstagaca gtagtaatag ggaagaat3t aagaatttca taattcagat ttcaataaaa 34920 attgagaaaa aataaattta aaaacggttg atattctttt gtttaagcag acaagtatgc 34980 gga = gtgaat cttgagcacc tcgtaaa ca cgggaggcgt acttgcacag aagagagata 3S040 acggattaag aggcgcaagc tttgccac t tgaasttaaa aaataaagaa to agacatqc 35100 aaattggtgg acaaatagcg gaaggttagc gggaggtggg aggggggaca ggtgcatgta 35160 ttttacaata acacaatgga ggaatattsa aaatacgcat atgggasatc ggaacagata 35220 tgaaggtgtc aatatttgag gtcaactgtc tggtttttcc cegatte tg aattttttga 35280 ataatteaca aasssagtgc gattgaaatt ggaaact? gt cgagaaaaga ataaggagtg 35340 atggtggcaa ttatgaattg caaaacacaa attetacatt tgtaccaaaa tgcccactaa 35400 ttcgcacaca aatcggcaca ttccacacaa attgcataca tattecacaa tggggaatat 35460 tttcsstatt tagattaata aagatgaaat aattgagttt tatttgtaat taaaatatrt 35520 ttctgcttat cattaattga aaatgttgaa ttacttttta atagacgeat catcaaagaa 355S0 cttcacccct gcattatcag gcaatcctac ataacctttc aacgttgtcg ttttaccaat 35640 tgcaecattt ctcgctactg gaacacgc ^ t actggaatac gat gacgatt CCAAT tggaa 35700 gaatatattg gtgcccggtt ggaagttaac aattgaattg ttgttaagcg ataaaggata 35760 acatccaaaa cacattgata gttcagttat gtatatccat ccgtataaat cttgcgatct 35620 tccactcacc aaaagctggt cgccatcttg tataggaatg aatggagtta aggatcecgt 35880 aacagtacga gttgtgagcg tagttccact gaaaattact aaatatttag ttcaaaggtt 35940 ttctgccact actttttggt tgcaacaact ctgagaaatt ttagttttca ccaaaatttt 36000 tcgattttgt acagaattgc acaatatatt ttggaatagc aagaaattgt tcagtgaatg 36060 tc = aatctga caaaaaaaaa tttttttaaa aggtgcctat caatttttaa aaatgttcta 36120 atattttgtt ggaaagtttc aataatttca ctacatctac tatttctttt ttaggcctat 36180 tttgggtatt caaaatatta accacacgac cttcaataca ggaaaactgt caaatttttt 36240 ttaaattatg aacaattaac tcactttaca ttttgtcctc cattccttgt agttaatata 36300 agacttccca acgcttcttg agaactattc gaaataatat aaatcttcga atttcttcct 36360 actatatatc ctagtgtgtt gctcgttgca acgtctagag tatccaatat aaacccacta 36420 taaagaaaaa gaaactgata taatagaaat atatttttca ttttttccaa atgactaaat 36480 aagacatttt gaccaacttc atatgcttaa aatca cgtca atcatgttga cagaactata 36540 tttttgatag aaaatgataa gaaatgcgac caaaatgcgt attttctccg tttgtcctct 36600 aattcacgta gaatsagtca aaacttggca tttgtcacag tgtgtcagac acaaggcaca 36660 zgcatzta ta caagacttta ccggactttt ttattattga gaícaaacca gattacagaa 36720 GACC Gagaa aggcaccaac atattgcaaa aaatatcaga aaaaaattaa aaatttcaaa 36780 caaactagga acccaaactt gagctaattc aaactttgaa atcatgttcc ataaccggta 36840 gcatttgttc ggtgacttgt ttgacagccc attgaaggaa gagaagtact cccgacaggc 36900 cgaaaeatat gaaatagccc aggccctcca ttagagaatg aggaagaaca tgatgtttga 36960 atggcacgta gagtactccg aatagagcag taagtccatt gatgagctsa aacagtaaat 37020 ttagtaaata aaccgaaaag tgttcaagga atggaagtaa accggaatta tccgagtatg 370BC ggecttttat agttttttcf ctttttttga ctccgttttt catcctatta aaataccacc 37140 gttttttcg agttccagaa aaaatattta aaaaatcatc cgaaatccga acacaaaatc 37200 tccaaggcaa cgaaggccac gttaacccta ctcggcaaat ctctcgtcct ggagcgcgga 37260 cggggcgcga ctagatcacg ggttcgcgct ccagtcaccc tttttttcgc gcttcttacg 37320 cgccacgtcc gcgcttcagg aggagc GAIT tgcggagtac cttttatgca ttcagactgg 37380 tacttaaaaa ttaatcgatt tttttaaaaa gtgtcataaa ctttttctac gtctttttct 37440 gacacaatgt tgaaccgtac tagattgttg taaacacggt cttcaaattc gattttcgcg 37500 aaaaaatttg aataattttt ttctaacttt tttcttttta aaatcttacc acacttagca 37560 aacaaccatg aagcacaact tcataagtgg atcctatttt tcgtttgaag aggcaaaata 37620 ctgaaaacaa aagagctgat atggagcaag acacgtggat ccagaagagt atacgcacaa 37680 ccacactatc cccttcgatt ttgacgcggt acagaattct ggaatttttt tttgaacttt 37740 aatggattgc gattcaaaag aaaacgtagc ttaatctcca gttaaagctg attttcattg 37800 ttagaaaaaa caaaatgtat ctcacgctaa taaggcggag agtattgtct gtagaaccgc 37860 catgattact gtagatgcat agagtgagaa tgagcacata taagcgctcg gctgtttttg 37920 aacgacaatc gaattggccg ccaccatctc attcttcgac ctcccgtttt atttctgaaa 37980 atatatgaca ctttttaaat gaattgacag aaatctgatg ctaactacat tttaacttgt 3804O to gagtggtt caaatgattc ataaagggaa tacaatttct gaacgatcaa agaagaaaga 38100 aaaaaaatat tggtgaatgt ataatttttt aggggtaaag taaataaata aacacaaggc 38160 cqasgattag caagagttt g gggataaccc ccgtgaagaa aaacatgaaa aaaaatggtt 38220 cgaaagaatt aaaaaaatcc tttcaaattt gagatccaaa ttttgttcat ctgttctgtt 38280 cgaacattga gcagaagaag cttttaccaa taaatccaaa atttgttaag agaatatagt 38340 tteaggatat cacccagttc aaaatagtag ttcaaaaact cgagtcttaa tttcttcagt 36400 atcegaattt ttacagtaca ttgatcgttt cgttatttga tcgccttttg ataaaacaaa 38460 aaatagataa tgaagctgcc aagtttaaaa aaatcggggc taaggctaat ggagcacaca 38520 ctacctggat cggtatatca gacttcatca attagtttta gatatctagc cagaaaagta 38580 cgtea = Gaag tcggatacga tttcttaaaa aatgtataaa cttaaaactt cgagatatcc 3? S4Q agactgtggc tctcaagctt cagtgcttgg agaaatagct taatagccag aatatgtctt 337C0 aaatttctta agaagtcgta acttttctga aaagtataaa tgttgct = ga tcaaacactc 3876C tagaaaacct teaccacttg agaatactcc agtctcaaat tttccctcga cgcggaagtg 3S820 tagaagggcg cgagattcag aagtaggtga aaattagacg gaaaactctc tcaaaattga 36880 aatcaatgaa eaggacaact gagacaatgt gcaggtgtat gtgtatgcac atggcaccca 38940 cgtacacgca tacatcttat gttagagaag tacgtgtgct ccgctcatca tgtcttctcc 39000 tctctcctaca tct acatttt ttgctccgtg agccasgccg ggaaaaacga cgacgacgac 39060 ggcgacgggg gacgactsct cgactctaat tggccctaaa tttttaggca cgcaagtaaa 39120 atgtatgttt gcgagagttg agagccccac cgccacgagg agaagtgggg gaagattccg 39180 aagagattcc cccccctcct tctgatcacc tcgtctttcc ttttttgttc catttccgtg 39240 aaaaagctgt ggaagggagg agaagaactt accggctaaa tggaaaaaaa ggaactctaa 39300 cttattctga ctctacggaa ataggaagcc tacttgtcaa ctcgcaca <ttagaccgcc; Ja 39360 tttgtagata tttctttttt caaatataaa ßactaactgc gtgtgatgca gcagatatct 39420 tgaattggaa agtgtcagtg ctcagaggga atagccaatc attgacagaa atttgactac 39480 atcaactaga ttcacaagga acatttgacg ccegaaacct aacaagaaaa atctacaatt 39S40 tgcagatccc tagattgatg ccaactttat taaaaactaa gtatacttat atatatacga 39600 tttttttaaa aataaacctg attgtctgaa tttctacaag attgcgacca aattttccgt 39660 cctaatatta atttccaaaa ggggtttcta ctaaaattca acgagaactc ttaacattat 39720 acacatggtt ggctatttta caccgccggc tcaaacttca ttctcagtcc tctgattttt 39780 ggtaaatc? to cgcctacgtc tcaacaatta gtttgtgcag aaaataagta aaaagagttg 39840 tgcacacata tgctccatct cacatcgcct gtaatgaaga cagatgacta ggttcggagt 39900 ggcgtagaaa tgtgcgaaat tcacggataa cagagatttt tgatgtttca tcagacttac 39960 acgttttgga agtatgaatt gggtctagac aacggagtgg cagatgetcg gaaaattttg ÍO020 cagaaaagag aacctaagag cgttgatggt ttggcgacta acgaacttaa aagaaaattg 40080 gtcattgaaa attttaaaat tttaaatttt gcttgcagtt catctttctc tattaacaaa 401 0 asctstcttg tagcttttcc caatttcagg caattaaaac atttcaa cte atccttctat 40200 tatggaagtt tatctctaat tgaaactctc caattttgat caaagaacaa acgttctcgt 40260 tgtttgaaaa aaaaaacagt tcttttttga aactcgcgcg caaattatta accaatcatc 40320 ctcstttgcg cgcaaaattg tagaaaaaat catttaaatt tatcaaaaat agtttaccat 40380 ttttcatata tctgatgagt caaaaatgcs ctggcaattg ttgttttctc tgaaatagca 40440 cataataatt gaactctacc cacataaagt tcgttctgaa aaacacctta caattattgt 40500 caccccaaga gattgagagc gggattagaa aaacggatgt aatctgtata ccttcgagat 40560 ccttgtataa tcgtttattt ccaatagcag gaaaattaca gctttttcta agtaagcggt 40620 gaaactagag agattctata gaatatgggc gttaataatt gtatgttaaa gttttagaat 40680 aacacaagtc cagagtaagg gcaagaaaag taatgagcaa cggaaaccag catgcaagac 40740 acccga ttc cggttctctt ctgaaactaa aagttgcgtg tactaaacct taaaccagca 40800 gctggctagt cccaagaaat aatagaaaaa aggaaggaat gaagatatgg gaataataca 40850 aattgaaaat gttgtgtgag ctc? gaataa ttttcaatat caaaaattta tgaattgtgt 40920 ggacggctgt gtgtgcgtgt gcgtatgcgt cggcaagaaa aagaagcgac cgaataagaa 40980 AATG? rttgat tcagtgaaca aaaaaagaga gaaagatat c caaacaaaat tatccaaaac 41040 tattatcaat cggtaggtat tgstctagag cacacctttc tggacactca geagaeatgc 41100 gtagagaggg attatgtggt acatatagcg gatggaggaa cagatattta taaatactta -31160 tgg = aaasag ggatgaggta gatgaaqata gaagatttta gatgaattga aaatgataat 41220 tttgaataag ggatattgaa attatccgaa gagattctaa tatatcaaga gaacacaaac 41280 atctagacga ctacaaaata gtcccagttt tgcaaggtaa ggattaatct taaaaggatc 41340 ttcteaatat ttatttcaat gctcctataa attttaaaaa gtaggtgcat tctaatatgt 41400 aca tgatta ggagatatgt gacgttacgt gaggtctcga taaegtacgg tattcgagct 41460 aaatttcaaa cattgtcaag gtagattcgg tacacagcca ccataaatgt tccactaaaa 41520 atgtgttgtc cttczccttt ggaacacaaa tctagctgct gaactttttc acttcactac 41580 atgtcaatgg gattgatatg catctaggac atttttttgg ttatcaatag tccgcatagc 41640 tecegtaacc aatacaaccg attgtccaaa aaaatttgaa cactacaaaa cgtatttatt 41700 attcggatac ccgttgcatt tcaatacaca agttgatact tgccgccccc cggggctctc 41760 agac = CCCat tgactgaaaa cagacgattg ctcgtcgtcg tagcccgaag gcccggagag 41320 ctgaggaaga tatgaggaca taatgaattg atgtgtgaga gaaaaaggaa atgagaaaae 41BS0 aaaaagatga aaatgagaaa tgaagaatgt acaaatgaat aatcaagtag caacgacgag 41940 aaaagaacca ggtccttttg gcaggcaatt ttcgaaattt tcagatcaaa tttgtcgcca 42000 ttgcttctgg attaataatg gatgacgctt tgacaatggt agtgcaaaca gctcaataca 42060 ggatggcgta gattggtttg tagaaataga gccggtgaga cgatgtgatg aagttctgag 42120 agacgagatg tgatcgaggc gtttgtagtc gaggcaaacc gaggccgcat atggggttcc 42180 gataggcaat cggagaccag tgtccatctg aaagagataa aagttattcg agttgtgaat 42240 gttgcaagga aaattaaagg tacagtagag acaatcgaga cttttttcgg gaggacgcca 42300 tetaaaaact gtggaagcac gtggctttgg tagcttgatg tcacagaagt tgattccata 42360 agaattacat ta AAAGCTT gcgacgctaa atggataaat ctggtaacgg cttcctaata 42420 gcaagttaag ttttttcaca ataaattttt cagaattgaa tagatgcatt ttataactta cacatcgagt gggcacgttg 42480 42521 gtggacaaga caagccccga t < 21C > 24 < 211 > 4434 < 212 > DNA < 213 > Unknown < 220 > < 223 > Description of the Unknown Body: Unknown < 400 > 24 gccgccctcg ccaccgctcc cggccgccgc gctccggtac acacaggatc cccgctgggc 60 acca3cagct ccaccatggg gctggcctgg ggactaggcg tcctgttcct gatgcatgtg 120 rgtggcacca accgcattcc agagtctggc gcgtgtttga ggagacaaca catctttgaa 180 ctcaccgggg ccgcccgcaa ggggtctggg cgccgactgg tgaagggccc cgacccttcc 240 agcccagcct tccgcatcga ggatgccaac ctgatccccc ctgtgcctga tgacaagttc 300 caagacctgg tggatgctgt gcggacagaa aagggtttcc tccttctggc atccctgagg 360 csgstgaaga agacccgggg cacgctgctg gccctggagc ggaaagacca ctctggccag 420 gtcttcagcg tggtgtccaa tggcaaggcg ggcaccctgg acctcagcct gaccgtccaa 480 ggaaagcagc acgtggtgtc tgtggaagaa gctctcctgg caaccggcca gtggaagagc 540 ttgtgcagga atcaccctgt agacagggcc cagctgtaca tcgactgtga aaagatggag 600 aatgctgagt tggacgtccc catccaaagc gtcttcacca gagaectggc cagcatcgcc 660 agactccgca tcgcaaaggg gggcgtcaat gacaatttcc agggggtgct gcagaatgtg 720 aggtttgtct ttggaascac accagaagac atcctcagga acaaaggctg ctccagctct 780 accagtgtcc tcctcaccct tgacaacaac gtggtgaatg gttccagccc tgccatccgc 840 actaactaca ttggcc ACAA gacaaaggac ttgcaagcca tctgcggcat ctcctgtgat 900 gagctgtcca gcatggtcct ggaactcagg ggcctgcgca ccattgtgac cacgctgcag 960 gacagcatcc gcaaagtgac tgaagagaac aaagagttgg ccaatgagct gaggcggcct 1020 cccctatgct atcacaacgg agttcagtac agaaataacg aggaatggac tgttgatagc 1080 tgcactgagt gtcactgtca gaactcagtt accatctgca aaaaggtgtc ctgccccatc 1140 atgccctgct ccsatgccac agttcctgat ggagaatgct gtcctcgctg ttggcccagc 1200 gactctgcgg acgatggct g TKWG ccatgg tccgagtgga cctcctgttc tacgagctgt 1260 ggcaatggaa ttcagcagcg cggccgcccc tgcgatagcc tcaacaaccg atgtgagggc 1320 tcctcggtcc agacacggac ctgccacatt caggagtgtg acaagagatt taaacaggat 1380 ggtg ctgga gccactggtc cccgtggtca tctcgttctg tgacatgtgg tgatggtgtg 1440 atcacaagga tccggccccg caactctccc tgaacgggaa agcccccaga accctgtgaa 1500 ggccaagcgc gggagaccaa agcctgcaag aaagacgcct gccccatcaa tggaggctgg 1560 ggtccttggt caccatggga catctgttct gtcacctgtg gaggaggggt acagaaacgt 1620 agtcgtctct gcaacaaccc cacaccccag tttggaggca aggactgcgt tggtgatgta 1680 acasaaaacc agatctgcaa c aagcaqgac tgtccaattg atggatgcct gtccaatccc 1740 tgctttgccg gcgtgaagtg tactagctac cctgatggca gctggaaatg tggtgcttgt 1800 ccccctggtt acagtggaaa tggcatccag tgcacagatg ttgatgagtg caaagaagtg 1860 gcttcaacca cctgatgcct caatggagag caccggtgtg agaacacgga ccccggctac 1920 aactgcctgc cctgcccccc acgcttcacc ggctcacagc gggtgtcgaa ccttcggcca 1980 ccaacaaaca cacgccacgg ggtgtgcaag ccccgtaacc cctgcaccrs tgggacccac 2040 agaacgccaa gactgcaaca gtgcaactac ctgggccact atagcgaccc catgtaccgc 2100 TGCG = gtgca agcctggcta cgctggcaat ggeatcatct gcggggag s cacagacctg 2160 gatggctggc ccaatgagaa cctggtgtgc gtggccaatg cgacttacca ctgcaaaaag 2220 gataattgcc ccaaccttcc caactcaggg caggaagact atgacaagga tggaattggt 2280 gatgcctgtg atgatgacga tgacaatgat aaaattccag atgacaggga caactgtcca 2340 acccagctca ttccattaca gtatgactat gacagagatg atgtgggaga ccgctgtgac 2400 aactgtccct acaaccacaa cccagatcag gcagacacag acaacaatgg ggaaggagac 2460 gcctgtgctg cagacattga cggagacggt atcctcaatg aacgggacaa ctgccagtac 2520 gtctacaatg tggaccagag agacac tgat atggatgggg ttggagatca gtgtgacaat 2580 tgccccttgg aacacaatcc ggatcagctg gactctgact cagaccgcat tggagatacc 2640 tgtgacaaca atcaggatat tgatgaagat ggccaccaga acaatctg to caactgtccc 2700 atgccaacca tatgtgccca ggctgaccat gacaaagatg gcaagggaga tgcctgcgac 2760 cacgatgatg acaacgacgg ca tcctgat gacaaggaca actgcagacc cgtgcccaat 2820 aggactctga cccgaccaga cggcgatggt cgaggtgatg cctgcaaaga tgattttgac 2880 catgacagtg tgecagacac cgatgacatc tgtcctgaga atgttgacat cagtgagacc 2940 gatttccgcc gattccagat gattcctctg gaccccaaag ggacatccca aaatgaccct 3000 tacgccatca aactgggttg gggtaaagaa ctcgtccaga ctgtcaactg tgatcctgga 3060 ctcgctgtag gttatgatga gtttaatgct gtggacttca gtggcaeccc cttcatcaac 3120 accgaaaggg acgatgacta tgctggattt gtctttggct accagtccag cagccgctct 3180 tgtggaagca tatgttgtga agtcacccag tcctactggg acaccaaccc cacgagggct 3240 cagggatact cgggcctttc tgtgaaagtt gtaaactcca ccacagggcc tggcgagcac 3300 ctgcggaacg ccctgtggca cacaggaaac acccctggcc aggtgcgcac cctgtggcat 3360 gaccctcgtc acataggctg gaaagatttc accgcctaca gatggcgtct cagccacagg 3420 ccaaagaegg gtttcattag agtggtgatg tatgaaggga agaaaatcac ggctgactca 3480 ggacccatct atgataaaac ctatgctggt ggtagactag ggttgtttgt cttctctcaa 3540 gaaatggtgt ccttctctga cctgaaatac gaatgtagag atccctaatc atcaaattgt 3600 tgattgaaag actgatcat = aaccaacgct ggtattgcac cttctggaa tatgggcttg 366c agaaaacccc caggatcact tctccttggc ttccttcttt tctgtgcttg catcagcgtg 3720 gactcctaga acgtgcgacc tgcctcaaga aaatgcagtt ttcaaaaaca gactcagcat 3780 atgaataaga tcagcctcca catcttccaa gcatataaac aattgctttg gtttcctttt 3840 gaaaaagcat ctacctgctt cagttgggaa ggtgcccatt ccactctgcc tttgtcacag 3900 agcagggtgc tattgtgagg ccatctctga gcagtggact caaaagcatt ttcaggcatg 3960 tcagagaagg gaggactcac tagaattagc aaacaaaacc accctgacat cctccttcag 4020 gaacacgggg agcagaggcc aaagcactaa ggggagggcg catacccgag acgattgtat 4080 gaagaaaata tggagg aact gttacatgtt cggtactaag tcattttcag gggactgaaa 4140 gactattgct ggatttcatg atgctgactg gcgttagctg attaacccat gtaaataggc 4200 acttaaatag aagcaggaaa gggagacaaa gactggcttc tggacttcct ccctgatccc 4260 cacccttact catcacctgc agtggccaga attagggaat cagaatcgaa accagtgtaa 4320 ggcagtgctg gctgccattg cctggtcaca ttgaaattgg tggcttcatt ctagatgtag 4380 tgtagcagga cttgtgcaga aaataggaaa acctaccatc tcagtgagca ccag 4434 < 210 > 25 < 211 > 2837 < 212 > DNA < 213 > Unknown < 220 > < 223 > Description of the Unknown Body: Unknown < 400 > 25 agagagccag tccgatgtct gcagcctccc tggccaggcc tctcctctcc tgccgcagct 60 agtccccctc aggacagaca gagtactggc gtcggtcacc attcacttge aaacacacca 120 ggtcacgtga agaaacttcc tggtgacact caggctgtag ctgtgcactc ttcaaccacg 180 aggttggttt tctcctaagt gtcacaggtg gagacaagat gctctgggca ctggccctgc 240 tggccctggg catagggcca agagcttctg ctggtgacca cgtcaaggac acttcarttg 300 acctctccag catcagcaac attaaccgga agaccatcgg tgccaagcag ttccgagggc 360 ctgaccccgg ggtgcccgec taccgttttg tacggtttga ctacatcccc ccagtgaaca 420 cagatgatct caacaggatt gtcaagcttg caaggagaaa ggagggcttc ttcctcacag 480 cccaactgaa gcaggaccgc aagtctcggg gaacgctcct ggtgtccgaa ggccccggca 540 cctcccagag gcagtttgag attgtgtcca atggcccagg ggacactttg gacctcaact 6O0 actgggtaga aggcaatcag cataccaact tcctggagga tgtgggcctg gctgactccc 660 tgtgactgtg agtggaagaa caggtggcca gtgacaccta tagcctgtat gtgggctgcg 720 atcttatcga cagtgtcacc ctggaagaac cattctatga gcagctagaa gtagacagga 780 cgtggccaaa gcaggatgta ggtgcatctc gagagagtca ttgctgcaga cttcaggggc 840 atgtccatct cgtgtt TGCA gattctgtgg aagatatctt aagcaagaaa agctgtcaac 900 acagccaggg agctgaagtc aacaccatca gtgaacatac agagactctc catctgagcc 960 cccacaccac cacagatccc gtggtccagg gtgtggagaa ggcacaggag gtgtgtacgc 1020 actcctgcga ggagttgagc aacatgatga atgagctctc tggactgcac gtcatggtga 1080 accagctgag caagaacctg gagagagtgt ctagtgataa ccagttcctt ttggagctca 1140 ttgggggccc tstgaagaca agaaacatgt cagcctgtgt gcaggagggc cgaatctttg 1200 cagaaaatga aacctgggtt gtggatagtt gtaccacatg cacctgcaag aaatttaaaa 1260 cagtctgcca tcagatcacc tgctcacctg caacttgtgc caacccatct tttgeggaag 1320 gcgagtgctg tccatcctgt tcacactctg cagacagtga tgagggctcg tctccgtggg 1380 cagag GGAC cgagtgttct gtcacctgtg gctctgggac ccagcagaga ggccggtctt 1440 gtgatgtcac cagcaacacc tgcctgggcc gacaaggaca cctccattca tgcagcctgg 1500 gcaaatgtga tacgagaatc cgtcagaatg gaggctggag tcactggtca ccctggtctt 1560 catgctccgt gacttgtgga gttggcaatg tcacccgcat acgtctctgc aacteaccag 1620 tgccccagat gggtggcaag aactgcaagg gcagcggccg ggaaaccaaa ccctgrcagc 1680 gtgatccgtg cccaattgat ggc cgctgga cccttggtca gcccctggtc gcctgcacag 1740 ttacctgtgc tggagggatc cgtgagcgct cacgtgtttg caacagccct gagccccagt 1800 ggactgtgtc atggaaggaa cagaacacca ggggatgtga aatgtgcaac aagagaagct 1860 tgggtgctta gccctattga tccaacccgt gttttcctgg agccaagtgc aacagcttcc 1920 ctgacgggtc ctggtcctgc ggctcctgcc cagtgggctt tctgggcaat ggtacccact 1980 gtsaggacct ggatgagtgt gctgtggtca cagatatttg cttccca = et aacaaagctc 2040 cccgctgtgt caacaccaac ccgggcttcc actgcctgcc ttgtccacca cgctacaagg 2100 ggaaccaacc cttcggtgtt ggcctggagg atgctaggac agaaaaacaa gtgtgtgagc 2160 cagagaatcc atgtaaggac aagactcaca gctgccacaa gaatgcagag tgcatctacc 2220 tgggccactt tagtgacccc atgtacaagt gtgagtgcca gattggctac gcaggtgatg 2280 ggctcatctg cggggaggac tcagacctgg atggctggcc caacaacaac ctggtgtgtg 2340 ctactaatgc cacctaccac tgcatcaagg acaactgccc caaactgcca aattccgggc 2400 aggaggattt tgataaggat ggaatcggag atgcttgtga cgaggacgat gacaatgacg 2460 gtgtgagcga tgagaaggac aaccgccagc ttctcttcaa tccccgtcaa ttagactatg 2520 acaaggatga ggttggagac cgctgtgac to actgccccta tgtgcacaac ccagcacaga 2580 tcgacacaga caacaatggc gagggggatg cctgctctgt ggacattgac ggagacgatg 2640 ttttcaatga gcgagacaat tgtccatatg tctacaacac tgaccagaga gatacggatg 2700 gtgatggcgt gggtgaccac tgtgacaatt gtcctctgat gcacaaccca gatcagatcg 2760 atcaggacaa tgatctcgtt ggagaccagt gtgacaacaa tgaggacata gatgatgacg caaccaa gccaccagaa 2820 2837 < 210 26 < 211 > 4108 < 212 > DNA 213 > Unknown < 220 > < 223 > Description of the Unknown Body: Unknown 400 > 26 agagagccag tccgatgtct gcagcctccc tggccaggcc tctcctctcc tgccgcagct 60 agtccccctc aggacagaca gagtactggc gtcggtcacc attcacttgc aaaeacacca 120? Gccacgtga agaaacttcc tggtgacact caggctgtag ctgtgcactc ttcaaccacg 180 sggctggttt tctcctaagt gtcacaggtg gagacaagat gctctgggca ctggccctgc 240 tggctctggg catagggcca agagcttctg ctggtgacca cgtcaaggac acttcatttg 300 acctttccag catcagcaac attaaccgga agaccatcgg tgccaaacag tcccgagggc 360 ctgaccccgg ggtgcccgce taccgttttg tacggtttga ctacatcccc ccagtgaac = 420 cagatgatct caacaggatt gtcaagcttg caaggagaaa ggagggcccc tccctcacag 480 cccaactgaa gcaggaccgc aagtctcggg gaacgctcct ggtgttggaa ggccccggca 540 cctcccagag gcagtttgag attgtgtcca atggcccagg ggacactttg gacctcaact 600 actgggtaga aggcaatcag cataccaact tcctggagga tgtgggcctg getgactccc 660 tgtgactgtg agtggaagaa gtgacaccta caggtggcca tagcctgtat gtgggctgcg 720 atcttatcga cagtgtcacc ctggaagaac cattctatga gcagctagaa gtagacagga 780 gcaggatgta cgtggccaaa gagagagtca ggtgcatctc ctgctgcaga cttcaggggc 840 atgtccatct cgtgtttgca gattctgtgg aagatatctt aagcaagaaa agctgtcaac 900 acagccaggg agctgaagtc aacaccatca gtgaacatac agagactctc catctgagcc 960 ctcacatcac cacagatctc gtggtccagg gtgtggagaa ggcacaggag gtgtgtacgc 1020 actcctgcga ggagttgagc aacatgatga atgagctctc tggactgcac gtcatggtga 1080 accagctgag caagaacctg gagagagtgt ctagtgataa ccagttcctt ttggagctca 1140 t cgggggccc tctgaagaca agaaacatgt cagcctgtgt gcaggagggc cgaatctttg 1200 cagaaaatga aacctgggtt gtggatagtt gtaccacatg cacctgcaag aaatttaaaa 1260 cagtctgcca tcagatcacc tgctcacctg caacttgtgc caacccatct tttgtggaag 1320 gcgagtgctg tccatcctgt tcacactctg cagacagtga tgagggctgg tctccgtggg 1380 cagagtggac cgagtgttct gtcacctgtg gctctgggac ccagcagaca ggccggtctt 1440 gtgatgtcac cagcaacacc tgcccgggcc gacaaggaca cctccattca tgcagcctgg 1500 gcaaatgtga tacgagaatc cgtcagaatg gaggctggag tcactggtca ccctggtctt 1560 catgctccgt gacttgtgga gttggcaatg tcacccgcat acgtctctgc aactcaccag 1620 tgccccagat gggtggcaag aactgcaagg gcagcggccg ggaaaccaaa ccctgtcagc 1680 gtgatccgtg cccaattgat ggccgctgga gcccctggtc cccttggtca gcctgcacag 1740 ttacctgtgc tggagggatc cgtgagcgct cacgtgtttg caacagccct gagccccagr 1800 ggactgtgtc atggagggaa ggggatgtga cagaacacca aatgtgcaac aagagaagct 1860 gc cattga tgggtgctta tccaacccgt gttttcctgg agccaagtgc aacagctt cc 1920 ctgacgggtc ctggtcctgt ggcccctgcc cagtgggctt tctgggcaat ggtacccact 1980 gtcagg acct ggatgagtgt gctgtggtca cagatat ttg cttctcaact aacaaagctc 2040 cccgctgtgt caacaccaac ccgggcttcc actgcctgcc ttgtccacca cgctacaagg 2100 ggaaccaacc cttcggtgtt ggcctggagg atgctaggac agaaaaacaa gtgtgcgagc 2160 atgtaaggac cagagaatcc aagactcaca gctgccacaa gaatgcagag tgcatctacc 2220 tgggccactt tagtgaccsc atgtacaagt gtgagtgcca gattggctac gcaggtgatg 2280 ggcccatctg cggggaggac tcagacstgg atggctggcc caacaacaac ctggtgtgtg 2340 ccactaatgc cacctaccac tgcatcaagg acaactgccc caaactgcca aattccgggc 2400 aggaggattt tgataaggat ggaatcggag atgcttgtga cgaggacgat gacaatgacg 2460 gtgtgavjcga tgagaaggac aattgccagc ttctcttcaa tccccgtcaa ttagactatg 2520 ggttggagac acaaggatga actgccccta cgctgtgaca ccagcacaga tgtgcacaac 2580 t cgacacaga caacaatggc gagggggatg cctgctctgt ggacattgac ggagacgatg 2640 ttttcaatga gcgagacaat tgtccatatg tctacaacac tgaccagaga gatacggatg 2700 gtgatggcgt gggtgaccac tgtgacaatt gtcctctgat gcacaaccca gatcagatcg 2760 atcaggacaa tgatctcgtt ggagaccagt gtgacaacaa tgaggacata gatgatgacg 2820 gccaccaga to caaccaagac aßctgcccat acatctccaa ctccaaccag gctgaccatg 2B80 acaacgacgs caagggcgat gcctgcgact ctgatgatga caatgatggt gttccagatg 2940 acagggacaa ctgtcggctt gtgttcaacc cagaccagsa agact cggac ggtgacggcc 3000 gaggtgacat ttgtaaagat gactttgaca atgataatgt cccagatatt gatgatgtgt 3060 gccctgagaa caatgccatc actgagacag acttcagaaa cttccagatg gtccctctgg 3120 gaccacacaa atcccaaggg attgatccca actgggtaat tcgtcaccaa ggcaaagagc 3180 agcaaactca cggcgcagac gaccctggca tcgctgtagg tttcgacgag tttgggtctg 3240 tggacttcag tggcactttc tatgtcaaca ct? accggga tgatgactac gctggctttg 3300 tcttcggcta tcagtcaagc agccgcttct atgtggtgat gtggaagcag gtgaccr.aga 3360 cctact? gga agacaagccc ogtcgggctt acggctactc tggtgtgtca ctcaaagtgg 3420 taaaccccac gactggtact ggcgagcacc tgaggaatgc cctgtggcac acgggaaaca 3460 cagaaggcca ggtccggact ctatggcatg accccaaaaa cattggctgg aaagactaca 3540 ctgcctacag gtggcacctg attcacaggc ctaagacagg ctacataaga gtcttagtgc 3600 atgaaggaaa gcaagtcatg gctgactcag gaccaattta tgaccaaacc tacgctggtg 3660 gacggctggg cctgtttgtc ttctcccaag agatggtcta tttctcggac ctcaagtatg 3720 tgcctagaga agcgcagaga gcagggctcc agctccagca atgtgctgca aacacccctt 3780 cttagacaca tcagtccatc ttggcacttg tggcttttct gtcatttggc atttcctgtt 3840 tcttgacctt aactgagtgg atctacacct ccttcatcag caccaagtcc aagtgtcttc 3900 aaaggagaaa catcaattgc actccaagag cctccagcct gctgctggaa aacatctgga 3960 ggctcaccgt tgagatatga ggagcgaaga ccgagcattc cgctgtgttg ccttttcttg 4020 tttgtttaaa aagaacgacg tttacatgta aatgtaatta cttgcagtat ttatgtgtat 4080 agggagcttt atggagtcga agagcaca 4108 < 210 > 27 < 211 820 < 212 > DNA < 213 > Unknown < 220 > < 223 > Description of the Unknown Body: Unknown < 400 > 27 tcgaccagag gaggggaggc cagttcctct cccaagggtg ccacacaccc ctccctgttc 60 atcaccagac aggcccttcc ttcttaqcca tacgctaacc ttctcccccc tgggaaatct 120 cctct? CAGG agccaaagea gatgcgagct ggagttgctg gagctcctgg tctgtatgca 180 gagcaggcat ccaggaaagg agaagagagt gtgacaaccc agcacctcag aatggagggg 240 cctcgtgttc agggcggaaa gtacagacgc aggcttgctg agggcctctg gacacaggct 300 ggaccagacg ctgcggatgt cgacccctgc act actatt ggataaagac ttctttcaac 360 taagasaaga tgcaaatcag cacacttttt tctttgttct gccagcttcc aggcctaaga 420 ctaggttttg ccgtctacag ccaactattc tattagttac aaaactcaat cattttattc 480 ascaactgga tgttgactgt taactagaag ctctgtccta cctacagcac cttggatcat 540 aagtaaaata caaaaaaata gaaaactgag aaaactcaat ccatgaccag ggagaactta 600 caggatgtta gagacaaaac aagcagacac ctgaaacaat caacgcccaa taaaacaaag 660 attctcttag taggatgaaa ttctttgata acaatttgtc cactcataga aacattatta 720 taagcagaca attggtaggg ctctgaaaca atgagaaaaa tactaaasat tgacttgagc 780 tatttcaaat tgcctcattg acctgttata tcataactct 820 < 210 > 28 < 211 > 2397 < 212 > DNA < 2i3 > Unknown < 220 > < 223 > Description of the Unknown Body: Unknown < 400 > 26 tttttttttt catcctactt tgttttattg ggcgttgatt gttacaggtc ccagcctgta 60 gacatctttt actccaattt cctgaataga tagctttacc cctccaaggt aatatagtgc 120 ggtggcttct ggctgagatg tttgctgttg ttttcttcat cttgtctttg atgacttgtc 1B0 agcccggggt aactgcacag gagaaggtga accagagagt aagacgggca gctacacccg 240 cagcagttac ctgccagctg agcaactggt cagagtggac agattgcttt ccgtgccagg 300 acaaaaagta ccgacaccgg agcctcttgc agccaaacaa gtttggg ga accatctgca 360 gcggcgacat ctgggatcaa gccagctgct ccagttctac aacttgtgta aggcaagcac 420 agtgtggaca ggatttccag tgtaaggaga caggtcgctg cctgaaacgc caccttgtgt 480 gtaatggaga ccaggactgc cttgatggct ctgatgagga cgactgt aa gatgtcaggg 540 ccattgacga agactgcagc cagtatgaac caattccagg atcacagaag gcagccttgg 600 ggtac = atat cctgacccag gaagatgctc agagtgtgta cgatgccagt tattatgggg 660 gccagtgtga gacggtatac aatggggaat ggagggagct tcgatatgac tccacctgtg 720 aacgcctcta ctatggagat gatgagaaat accttcggaa accctacaac tttctgaagt 780 agccctggca accactttga gatactggaa tctcctcaga gttttatgat aatgcaaatg 840 accctctttc caaagtt aaa aaagacaagt ctgactcatt tggagtgacc atcggcatag 900 gcccagccgg cagcccttta ttggtgggtg taggtgtatc ccactcacaa gacacttcat 960 tcttgaacga attaaacaag tataatgaga agaaattcat atcttcacaa tttcacaaga 1020 aggtscagac tgcacatttt aagatgagga aggatgacat tatgctc 't gaaggaatgc 1080 tgcagccatt aatggagctt ccagatcagt acaattatgg catgtatccc aagttcatca 1140 atgactatgg cacccattac atcacatctg gatccatggg tggcatctat gaatatatcc 1200 caaagcaaaa tggtgattga atggaatccc ttggtattac cagcagagat atcacgacat 1260 gtttcggagg ctccttgggc attcaatatg aagacaaaat aaatgttggt ggaggtttat 1320 caggagacca ttgtaaaaaa tttggaggtg gcaaaactga aagggccagg aaggccatgg 1380 ctgtggaaga cattatttct cgggtgcga? gtggcagttc tggctggagc ggtggcttgg 1440 cacagaacag gagcaccatt acataccgtt cctgggggag gtcattaaag tataatcctg 1500 ttgttatcga tcctgagatg cagcctatcc acgaggtgct gcggcacaca agcctggggc 1560 ctctggaggc caagcgccag aacctgcgcc gcgccttgga ccagtatctg atggaattca 1620 atgcctgccg atgtgggcct tgcttcaaca atggggtgcc catcctcgag ggcaccagct 1680 gcaggtgcca gtgccgcctg ggtagcttgg gtgctgcctg tgagcaaaca cagacagaag 1740 gagccaaagc agatgggagc tggagttgct ggagctcctg gtctgtatgc agagcaggca 1800 tccaggaaag gagaagagag tgtgacaatc cagcacctca gaatggaggg gcctcgtgtc 1860 cagggcggaa agtacagacg caggcttgct gagggcctct ggacacaggc tggaccagat 1920 gctgtggatg tcgacccctg cactgactat tggataaaga cttctttcaa ctaagagaag 1980 atgcaaatca gcacactttt ttctttgttc tgccagcttc caggcctsag actaggtttt 2040 gctgtctaca gccaactatt ctattagtta caaaactcaa tcattttatt cagcaactgg 2100 ttaactagaa atgttgactg gctctgtcct acttacagca ctttggatca tcaaaaaaat 2160 agaaaactga aaagtaaaat gaaaactcaa tccatgacca gggagaactt acaggatgtt 2220 caagcagaca agagacaaaa cctgaaacaa tcaacg ccca ataaaacaaa gtaggatgaa 2280 aattctctta gttctttgat aacaacccgt tcactcacag aaacatcatt aartggtagg 2340 gtaagcagac actctgaaac aatgagaaaa atactaaaaa ttgacttgag ttatttc 2397 < 210 > 29 < 211 > 4100 < 212 > DNA < 213 > Unknown < 220 > < 223 > Description of the Unknown Body: Unknown < 40C > 29 ggatcccccc gctccgctac catcttcatc gacctcaccc aggacgacga ctgagctccc 60 tcttcctcgc cgcggactgg ggcgaccctg ttgctgctgc ggccgccccc gctcctgccc 120 ccacttcggc tccsgctcct gctcctgctc Ccggccccac tcctgttcct gttcctgttc 180 ctgttcctgt tcccggtcct gctccggctc ccggccccgc acccacctcc gctcctgctg 240 ggcccagaca cgggtctcca aaataaaaaa agatatattt tttcagtccg tctctcccgc 300 ccggtgtctt ctatggctga gggagtctgg ctctcggggc tctcgggtcg gctgggcggc 360 tcggctggtt ggctggctgg cgagatggac cgctccggcg cgcagcgtec gcggctgctg 420 tgatggátgg gcggagcgcg gaccggggat tatatacacg atgtgcatcc ataattgatg 480 ttgcctgaga aaaacaaagt cataaagtgg cactcagaca gcactttggc ctggcgcccg 540 gccaccatct gagtgcccaa ccgggcccgg cggttácate acccccacat ggaccatcac 600 ggcccattag caccaattgg ccagagtgtc gggagccacc gctaattg to gtaacgcgcg 660 gctgccagac tgcaatttac cgcgcgatac tgcagtttac tgcagccgcg gtaaactgca 720 gtacgcggcg gccgcaggaa atctactgta gtatttggcg gcggcgcgcg gtactgcaac 780 tgtagctgca tgtagtaaac gtagagttac tgcagcgcca gtggccgcca tcgggccggt 840 gggtaactgc acccg ledder aatttactgc agccggactt tgtgcgctgt ggagaccgcg 900 ccgaactggg acccccccga ctcccccccg actccccecc gactcccccc cgactccccc 960 ccgactcccc cccgactccc ccccgactcc cccccgactc ccccgggacg cgtccgcgcc 1020 tcgatgcgcc ccatcgcgcc ccsttccgct tcgccacgct ccagttgccc cgcccccggc 1080 acgtggcacg tatttccccc ccgtaaatca agagggatta tgcggatgtc tagtttatgt 1140 ctcaatttcc tctttccgga gataaaagcc gggacccccg ggatacacca cgccgaaaaa 1200 gccgcgatgt cgccgctcgt GGCG? tgctg gtgttttttt cggcggccct gggggttcct 1260 ggccccggcg tcgcgggaaa cccccgtggg cccgatgcca tctccgaggc cccggtcacg 1320 cccgcscccc ccactcgcca tcctcggcgc gaggagctgg agtgggacja tgaggatcac 1380 ccgctgctgg acctcgagcc gcccgtggga tcacgctgcc atccctacst cgcgtactcg 1440 ccgccgccgg acatgaacgc cgtcacgagc gcggtcgcga agccctactg eccgcegceg 1500 gaggtcatcc tgtgggcgtc tggcaccgcc tacctggtca acccctttgt cgccatccag 1560 gccccggccg tcggagagcc cttaaatgag gcggccctca aggagctcgg agaggtggcc 1620 gtgcacaagg actccctgcc gccgctgcgc tataatggag ggccccccgc cgagtaagag 1680 accctgcggc ctgccgcccg g ggtgcgcct cgtcgtgcct gccgccgccg ccgcttstgc 1740 etctaacgcc gccacegccg ctgcagcagc agecccegcc ggggccgggg ccggggcctc 1800 gaagccggcc cgaccccccg ccgccgcccg gcccgcgaag ggcacgcceg cggcgtcggc 1860 ggcaacaaca gccacggggg ccgacgcctc cgccccggcc cccgaccccg gggcgcccac 1920 gtgggacgcc ttcgccgccg agttcgacgt ggccccctcg tggcgcgcgc tgctggagcc 1980 cgagatcgcc aagccgtacg cgcgcctgct gctggccgag taccgcggcc gctgcctgac 2040 cgaggaggtg ctgcccgcgc gcgaggacgt gttcgcctgg acgcgcctca cggcgcccga 2100 gtggtcatea ggacgtcaag tcggccagga eccgtaccac gggccgggcc aggcccacgg 2160 gctggccttc agcgtccggc gcggggtgcc gatccccccg agcctggcca acatcttcgc 2220 ggcggtccgg gcgacgtacc cgacgctgcc cgcgcccgcc cacggctgcc tggaggcctg 2280 ggcgcgccgc ggggtgctgc tgctgaacac gacgctgacc gtgcggcgcg gggtccccgg 2340 ctcccacgcc ccgcccggct gggcgcggct cgtgcgcgcc gtcgtccagc ggctctgcga 2400 gacccgcccc aagctggtgt teatgetetg gggcgcccac gctcaaaagg cctgcgcgcc 2460 ggacccgcgc cgccacaagg tgctcacctt cagccatccg tcgccgccgg cccgcacgcc 2520 cttcaggacc tgcccgcact ttggaga ggc gaacgcgtac ctcgtccaga cgggccgggc 2580 ccccgccgac tggagcgtgg actgagtcgg gcgtgcgcgc acaccgccgg cggaggacga 2640 ggagggggga ggggggtggg atggacggag gagagcggat gatggagccc gcgctcgccg 2700 gcgccccggc cagcgcgctg ccggtcctgg cggtgctgcg cgagtgggga tgggccgtgg 2760 aggaggtcga gccctccggg ccgtgcccgg aggacgcgga cgcgccccgg gagagcgcac 2820 cccctccccg ggagggggtg cgcgggagcg aagacggaga ggggggcgcg gaagacggcg 2880 ggcgacggag aggaggggaa aaggaggaga cggaagacga ggaagacggg ggggacgaag 2940 GGAC acgac ggcggcggcg ggcccgcgcc gggcgcagca cgtggagctt gacacgctgt 3000 ttstcgtcgc gtccgtggac gagctcgggc gccggcggct gacggacaog atccgccggg 3060 acctggccgc ggccctggcc ggcctccccg tcgcctgcac caagacgtcc gcgtttgcgc 3120 gcggcgcgcg cggcccgcgc ggcgcccccg ggcgcggcca taaaagcctg cagatgttta 3180 tcctgtgccg cagagcccac gcggcgcgcg tacgcgatca gctccggtcc gcggtgcgcg 3240 cccsacgccc acgcgagccc cgcgcgcgcc cgacgagcgg acgggcgcgg ccggccgcgc 3300 cggtgutcat ccacgagttc atcacccccg agceggtgcg gctgcaccgg gacaasgtgt 3360 ttgcggcgcc atgagcacct tcggacgcgc gtccgtggcc acggtcgatg actaccaccg 3420 gttcctgcag gccaacgaga cggccgcccg gcgcctggcc gcggcctccc gccgcgtctc 3480 caccggcggg ggcgagacgc gggccccgcg gtcctcgcgc ggcccccacg acgatgaggc 3540 gcccctgcgc gccggcggcc tgggcaccgc ccgcgggcgc tcgcgccagc gcggcgcgac 3600 cgagccggac cccgtctacg ccaccgtcgt ccagcctacc caccaccacc accagcagca 3660 ccaccaccgc tctcagcatc cgcagcagca gcaacaacag cagcgggccc cacgccgccg 3720 cggcagcgtg cacgcctcgg cgacggccgc ggacggaccc gagtcgtgcg cggccgcacc 3780 cccgcgccgc cgcggcagcg tgcacgcctc ggcgacggcc gccccggcgg tccagctgcc 3840 ccggccccgg caacggagca tcaacgcctc gacgacggcc gccccgacgc cccagctgcc 3900 gagaccccgc cagcgcagcg tcaacgcctc ggcccgcgcc gccgtcccct cgacggccac 3960 cctcccgcgc ccccggaccc cgtcccgggg ccggcgcgcg ccccccgcct catgctgtta 4020 taaagggcga tcgcgatcaa gcgcccacgg accagacaaa agacacaacc ggttcggtct ctctgtccgc gcacgcgcgg 4080 4100 < 21C > 30 < 21i > 38734 < 212 > DNA < 213 > Unknown < 220 > < 223 > Description of the Unknown Body: Unknown < 4C0 > 30 gatcctcgtg accgggtaca ccgacgcctc ctggacgccg ctgttcgcca tcgcgggcgg 60 ggtcgtcacc gacatcgggt cgatgctctc gcacagttcc atcgtggccc gcgagttcca 120 cgtcc CGCG GCGG gaaca ccaaggacgc, cacccagcgc atcaacaccg gcgacccgat 180 cgcggtggac ggcgacgcgg gcacggtcga ggtcgtcgag agcgcggaca ccgacccgca 240 gggcccggcc ggggccgccg ggaccccggc cggagccacc accgactgaa gccggccacc 300 cggaccacga gccgcaacac ccgcccccgc gaggggcgga ccacacccca gacgggagac 360 tccccaacca gacccgatga gtggtatccc atcgtcgagg cgcaggaggt gggcaacgac 420 aaaccgctcg gtgtgcgccg catgggccag gacctcgtgc tctggcgcga catcgacggc 480 aacctcgtct gecagggcgc cegctgcecg cacaagggcg ccaacctcgg cgacggccgc 540 acaccatcga atgaagggca atgcccgtac cacggcttcc gctacggagc cgacggcgcc 600 tgccgggtga tcccggcgat gggctccgag gcccgcatcc ccggctcgct gcgggtaccc 660 acctacccgg tccgggagca gttcggsctg gtgtggatgt ggtggggcga cgagegeccg 720 acggccgacc tgccgccggt ggcggccccg gccgaggtga sggacaaccg gaagctgtac 780 gccaccaagc gctggacccg cccggtgcac tacacccgtt acatcgagag cctgctcgag 840 ttctaccacg tgacct ACGT gcaccgggac cactggttca actacatcga ctacctgctc 900 ccccgagcaa ctgtacggca gttcggcctc gacggccgcg agcggtacct ggccgccacc 960 cggatcacca accaccgggt ggagacggag gcggaggggc agaccatccg ctactccttc 1020 gaccactgcc aggaggacga ccccaccaac accacccact acgtcatcac gttcaccttc 1080 tgcacgtgca ccgtgcatgg ttcgagacca gaccgagcag cctcctggct ggtgcccatc 1140 acaccgagca gacgaccaga catcctgegc tggtacgagt acgaacaggc caagcccgtc 1200 ctgacgttcg aaccgctgcg ccgcctcctg ccctgggcgt ccctctacat ggagaagtgg 1260 gtgcsggacc cccaggacgt ccgcatcatg gaacaccagg aacccaagat cagcgccggc 1320 ggcgtgaaca agttcatscc cgtcgacgag atgaacgcca agtacatctc gatgcgcgcc 1380 aagctgatcg cggacgcctc ggccgcgccc tcgtcaccgg cgcgggcggc ggagcccgag 1440 ccggaegcgg cggggcgggg cggatcagcg gcccgtgcca cgggcaacgg caggggagcg 1500 gccggcggac gacgcggcac caagcccaag gaggacgccg ccgcgcgccc gtagacccga 1560 agaccgcgga cggacaagag agagcgagag tgagagatgt acggcggata cgacgcgtcg 1620 accggeeeca aggccctggt gacggccttc aacaccgtcg ccgtggcegg cgccgtgtgg 1680 ttcctgttcg gcggcgcgga " AC ccgtggcc gactggttcg gcaccgaccc cgacgaggcg 174C gtgaccctgc gccgggtcct gctggcgacc ctgtcggtgc tctacctg t gcgcttcatc 1800 gccacgaact tcgtgatgct ccagcgcaag atggagtggt cggagtcggc caccatcggg 1860 atctgggtcc tggtgatcca cggcacgatg gcgtacttcg gcggcaccaa cgacgccggc 1920 GTGA cgcgt tcacctggct gggcgtcgtg ctgtacctcc tcgggtccta cctgaacacg 1980 gggtcggagt accagcgcaa actctggaag aagcgcccgg agaacaaggg caagctctac 2040 accgaaggcc tgttcaagca ctcgatgcac atcaactact tcggtgacgc cgtgctcttc 2100 tccgggttcg cgctggtcac gggcaccccg tgggccttcg ccatccccct gatcatggtc 2160 tgcatgttcg tcttcctgaa catccccatg ctcgacaagt acctcgccga gcgatacggc 2220 gaggccttcg acgagtacgc gtcccggacg gcgaagttcg tcccctacgc gtactgaecc 2280 cgcccgtcac gcgcgtacgg cggcctcccc gggcgagggg ccgggtggca ggccgccgta 2340 accacagatc ccacagatcc ccacagatcc ccacagagcc cctccacaga ccccctccag 2400 agatccacag atcccctcca cagatccgag acgaggcacg tatgaccgga gacattccct 2460 tcggagaggc cgaggcgtcc ctgaccgccg aggtgctgcg cgaggtcctg gccggcggcg 2520 ccgaggcgtt cgcccggctg acctccga cg agggcgccgt cgacgacttc ggcttcgacc 2580 cggagctgac cgacgastac ctgctccccg ccctgcgcct gctgtacgag aagtacttcc 2640 gggtcgacct ggagggactg gagaacgtgc cggccgaggg gggcgcactc Ctggtcgcca 2700 accactccgg caccctgccg ctcgacgcce tgatgctcca ggtggcgctg cacgaccacc 2760 acagcacgca ccgcaggctc cggctgctcg ccgccgacct tgccttcgac ctccccgtcg 2B20 tccgtgacct cgcccgcaag gccggccacg tacgcgcctg ccccgagaac gcgctgcggt 2880 tgcccggctc cggcgaactg gtcggc? tga tgccggaggg ctacaagggg ctcggcaagc 2940 ccttcgagga gcgctaccgg ctgcagcgct tcggccgggg aggcttcgcg gcggtggcac 3000 tgcggccgcg gcgccccatg gtgccgtgct cgatcgecgg cgccgaggag atctacccga 3060 tgatcggctc ggcccccacc ctggcccgga tgctgaagct gccgtacttc ccgatcaccc 3120 cgaecttccc gctgctgggc gcgctgggcc tgatcccgat gccgaccaag tggaccatcc 3180 gctceggtgc cccgatccac acggacggct tccccgagga cgccgcggag gacccgccgg 3240 tggtcgagaa gctcgccggc gaggtgaagg acaccatcca gcacacgctc aacgagatgc 3300 tggagggccg cggctccccg ttcgtctgag ggccgcggct cccggttcgc ccgagggcgg 3360 cggctcccgg ttcgcccgag gaccgtccct ctcgtccggg gccccgcctc agccccccgc 3420 cgacgatccc cggcggcaga tgctgcgaac gctggcgaag gccagaacgg cgaggccgac 3480 gagcgtgacg ccgccgccga ccagctccgc ggacagatgc atgggatctc cctcaggggg 3540 acgacggacg gtgatggtca tatagccatg cgaaccccgc cgtccgcccg atccgcagcc 3600 gcaccgcccc gcgaattcac ccgtagagca gaccggtgcg gccgaggagg ggtggcgatt 3660 gggtggtcgc gcgttcgaac gcttacgatc ctctgttgtg tccaaactga ccgacgtgcc 3720 caagcggatc ctcatcgggc gcgcactgcg cagcgaccgg ctgggtgaaa cgctcctgcc 3780 gaagcgcatc gcgcttcccg tgttcgcgtc cgacccgctg tcctccgtgg cgtacgcgcc 3B40 cggcgaggtg ctgctcgtcc tgtccatcgc gggcgtgtcg gcctaccact tcagcccgtg 3900 gatcgcggtc gcggtcgtgg tcctgatgtt caccgtggtc gcstcctacc ggcagaacgt 3960 gcaegcctac ecgagcggcg gcggcgacta cgaggtggcc accaccaacc tcsggeccaa 4020 ggccggtctg accgtcgcca gcgccctgct ggtcgactac gtcctgaccg tcgcggtctc 4080 catctcctcc ggcatc gaga acctgggctc cgcgatcccc ttcgtcgtcg agcacaaggt 4140 cctgtgcgcg gtcgccgtga tcctgctgct cacgctgatg aacctgcgcg gggtcaggga 4200 gtcgggcacc ctgttcgcga ttccgacgta cgtcttcgtc gegggcgtct tcatcatgat 4260 cgtgcggggg gcgtcccgcg gactggtcct ggacgacacc atgcgtgccc cgaccgcgga 4320 ctacgagatc aagccggagc acggcggcct ggccggcrtc gcgctgatct tcctcctcct 4380 GCGC ccttc tcctccggct gtgccgcgct caccggtgtc gaggcgatct ccaacggcgt 4440 cccggccttc cgcaagccca agtccaagaa cgcggggaac accctcgcga tgatgggtct 4500 gctgcccgtc accatgttct gcggcatcat cgcgctggcc gccgcgaccg acgtgcggat 4560 gtcggagaac ccggccaccg acctcttcca caacggcgtc gcggtcgscg cggactacgt 4620 ccagcacccg gtgatctcgc aggtcgccga ggcggtcttc ggcgagggca gcttcccgtt 4680 catcgtgctg gccgcagcca ccgcgctggt cctcttcctc gccgccaaca ccgcgtacaa 4740 cggctt CCCG ctgctcggct cgatcctcgc ccaggaccgc tacctgccgc gccagctgca 4800 cacccccggc gaccgcctgg ccttctccas cggcatcgtg ctcctcgccg gagccgccat 4860 gctcctggtc gtcgtctacg gcgccgactc gacccggctg atccagctct acatcgt cgg 4920 cgtctccgtg tccttcacg c tcagccagat cggcatggtc cgccactgga accgcaacct 4980 ggccggcgag cgggaccagt ccaagcgacg ccacatgatg cgctcccgcg cqatcaacgc 5040 cttcggcgcc ttctccaccg gcctcgtcct ggtggtggtc agttcacgca ctggcgacca 5100 cggcgcctgg gtcgcgctgc tcggcatgtg catcttcttc gcgaccatga cggcgatccg 5160 caagcactac gaccgggtcg ccgaggagat cgcggccccg gaggaccccg aggaggcaca 5220 gagcgßcgac atggtgcgcc cctcacgcgt tcactcggtg gtcctgatct ccaagatcca 5280 ccgccccacg ctccgcgccc tcgcctacgc caagctgatg cgctccgaca gcctggaggc 5340 gctcagcgtc aacgtcgacc cggccgagac gaaggcgctg cgcgaggagt gggagcgccg 5400 gtaccgctga cggcatcgcc aggtcctgga cgcgagatca cccgccgtac cccggccggt 5460 catcgagtac gtcaagagcc tgcgcaagga gtccccgcgc gacgcggtct cggtgatcat 5520 ccccgagtac gtggtcggcc actggtacga gcacctgctg cacaaccaga gcgccctgcg 5580 cctcaagggc cggctgctgt tcacgccggg cgtcatggtc acgtcggtcc cgtaccagct 5640 ggagtcctcc gaggccgcca ggcgccgggc gegcaagcgc caggactgga gcgcgccgg? 5700 tgcggtgcgg cgcggaccgg cccaccacca ccaggaccgt gaccgtacga aggactcctc 5760 ctcgtccacg tagactggac ggctgttgtc cctgtcatcc ccccgc cctc tggagtcacc 5820 ccgccatgca ggcagaaccg aagaagtcgc aggcggaaca gcgagcggtc gcggagccgg 5880 tctcggagcc ggtctcgctg gtgggcgagg agtacgaggt cgaggtcggc cccgtcgccc 5940 acggcggcca ctgcatcgcc cgcacgtccg agggccaggt gctgttcgtc cggcacacgc 6000 tgcccggcga gcgggtcgtg gcccgggtga cggagggcga ggagggtgcc cgcttcctgc 6060 gggcggacgc ggtcgagatc ctggacccct ccaaggaccg catcgaagcc ccctgcccct 6120 tcgccggccc cggccgctgc ggcggctgcg actggcagca cgccaagccg ggcgcccagc 6180 gacgcctgaa gggcgaggtg gtcgccgagc agttgcagcg cctggcgggt ctcaccccgg 6240 ag? aggccgg ctgggaeggc acggtgatgc cggccgaggg cgacaagctg cc? gccggcc 6300 aggtcccgtc gtggcgcacg cgcgtgcagt tcgcggtgga cgccgacggt cgcgccggtc 6360 tgcgccgcca ccgctcccac gagatcgagc cgatcgacca ctgcatgatc gcggcggagg 6420 gcgtcagcga actgggcatc gagcgccgtg actggcccgg catggcgacg gtcgaggcga 6480 tcgcggcgac gggctcccag gaccgccagg tcatcctgac cccgcgcccc ggcgcccgcc 6540 tccccatcgt cgaactggac cgcccggtct cggtcatgcg cgtcggggag aaggacggcg 6600 gcgtccaccg cgtccacggc cgcccctccg tccgcgagcg cgccgacgac cgcacctacc 6660 gcgtcggctc cggcggcttc tggcaggtcc acccgaaggc cgccgacacc ctggtcaccg 6720 cggtcatgca gggcctgctg ccccgcaagg gcgacatggc cctggacctc tactgcggcg 6780 tcggcctctt cgccggcgcc ctggccgacc gcgtcgggga ccagggagcg gtcctcggca 6840 tcgagtccgg caagcgcgcc gtcgaggacg cccgccacaa cctcgccgcc ttcgaccgcg 6900 tccgcatcga gcagggcaag gtcgagtccg tcctgccccg caccggcatc gacgaggtcg 6960 acctcatcgt cctcgacccg ccccgcgccg gcgccggccg caagacggtc cagcacctct 7020 cgaccctggg cgcccgcagg atcgcctacg tggcctgcga cccggccgcg ctggcccggg 7080 acctggggta cttccaggac ggggggtacc gggtgcggac gctgcgggtg ttcgatctgt 7140 tcccgatgac tgcgcacgtt gagtgcgtgg cgattttgga gcccgccgca aaggggctct 7200 gacctgcatt tttcttggct ggatcaggag cggcctgttg cgctcgacct gttctccaaa 7260 gcgcacgacg tagagcttgc ggaccgctcg tgaaagccgc ctgacctggc gttgcacgag 7320 cggtgccgcg- atgtcggcgc ggtcggcccc tctcctggcg cgaagggaaa ccgaaggtct 7380 tgacgctcgg gtgacgctat ttctgaaggg tcgtcaccga ctggggaggc .agggccctgc 7440 cgatgaagca ctctcgcgcc ggttctctct gctc caggta atcgtcgagg gtgccctgac 7500 ggatcaggta gacggccagg gaccgcaggg tgcagggcgt cgacgcccag gtcgaggatc 7560 atcagggcgc tgtcattggt gatggcgaag gcgccgatca caccgtcgac ggaacaggtt 7620 gcgttcagga gtctgtgcgg gcgccgcacc ggcacggtct ggaagctcgg ctccgaccgc 7680 cagtccgaga agctcgccac ggagccgata ctgtccggtg ccgggtgacc cttcgtgcaa 7740 gcgttgctgc ccccgctcgg cagaccgggg cagcaacgct tgcacgatcg gccggtactc 7800 aacgggatcg tgtggagttt cggaccggaa cggcttggca ggacgtgccc gagcggtacg 7860 gctcctgggc cacattgcac acccgcttcc gtcgatgggt gaaaggcggc acctttcagt 7920 gaaagggggt tccgcccccc cccgggacct tgcgcccacc gtcgccgacc ggctgatgaa 7980 gctcccgcca ccggctccgc ccaacctgac ccgacgtgag accgaagccc tctcaccggt 3040 cgccgacgga ctgtccgacc aggccatcgg cgcacgcctc cacttgaccg aaggcaccgt 8100 cgatatcacc tggcctgcat ctatgccaac ctcggaaccg actcgcgcac cgccgctgtg 8160 ccgccatcga gccactgtca cgacctcggg ctcatccgcc gctgaacagt atgtggtggg 8220 cggtgtttcc gttctccacg acttcagcgg cgtccggagt tgtggtgctg gctgggcttg 8280 gtgcccgctc ctctgaaccc atgtgaacgc ccacggcca g ttcgagccgg acacgccccc 8340 cggacctggc ctccgccgcg gccagaatgc ccggcccctg cacctggtct gcctacctgt 8400 acaggcgagg gcggtccctc ggagccactg cctgtaactc cgaggggccg cccttggccg 8460 actcgg ggt caccgcggac gcggtgcg t caggaggcac cgtctgcgtc atcaggcgcg 8520 gctcggccga gcgagttatt ccggcacccg tgggaccaga aatgtcagcc ctgcgtgacc 8580 gcttcgaaga ccgtgacgcg gttgtcgtcg gagagcgagt gggtggggtc ggcgtgcgcg 8640 gcgcggaatg cctccgacga ggtgtaggcg gtgaatgcgg cgtcgtcctc gaagttgagg 8700 acggccaggt agccgtgtgc gcccttgcgg ggacgcagca gccgtgcgtt gcgcagcccc 8760 ggcacgttgg aaagggtggc gcgcatgctg gcggtgcagt tgttctcgaa cgcgccctgg 6820 gcgggcgcgg cgacggtgaa ctcggtgacg gcggtgctca tttctgtetc cteteggttg 8880 ttggt gtgat gtcggtggct gtcccgcccg gccggggccc gcacggcgat ggsgatgatg 8940 tgcaccgcgt gtccgatcga gttccgttgc ggggcgcggt tacagggctg gagt tgggct 9000 cgggtccgcg gtcggctgag ggagcctgc tgtgcggcgg gcccagatt cgaacgcgat 9060 agtcatsaac gggggtacgg cggccagcag ggcgaagatc gttgtcc g Ccagccgcca 9120 cttcagccgg atcgcgacca ggacggt cag ggacacgtag acga tgaagg cggcgccgtg 91B0 gagggtgccg aagatccgta cgccgagttc ggtggtttcg gggatgcact tgaggtacat 9240 cccggccagc agacctgccc acgcgcacgc ttcgatgatc gcgatccagg tgaacgcgcg 9300 cagcagacgg ctggtgccgg tttcggcagc ccgtgcggcc ggcgcgtcgg cggaaggcgg 9360 ttcggaggtg ggcgtggagg gtgtctgcgg ggtgcctggg cgt gcgggc: acagggcgcg 9420 gttgccgagc aggcggacga tggcggggac caggagcggg cggatgagg = aggtgtccag 9480 caggatgccg caggccatgg cgaagccgaa ctggaacagt tcgcggaccg gctgggtcat 9540 csggacggcg aaggtcgccg cgaggatgag gcccgcggag gagatgacgc cgccggtgcg 9600 tgtcagtgcg gcggtgatcg ccttcgctgg gggctgggtg cgcagttcct gcttgaaccg 9660 gctcatgatg aagatgttgt agtcgacgcc gagcgcgacg aggaagacga agatgtacgc 9720 ggtgacgcgg ttgccgatgc cgtcgtcacc gaggacggtc acggtgaaga aggtggtggc 9780 gcccagggtg gccaggaacg acaggagcag ggtcgcgacc aggtagagcg gggcaaggag 9840 cgagcggagc agcaggacga ggaccacggt gacgatggct aggaccagca gcacgatgag 9900 ggtcgtgtcg cggtcgaggg cggagcggat gtcggcgttc tgcgcggtct cgccgccgat 9960 gagcaccgtg gcgccctgga cgccggcggc ctgggctgcg gattgtgt gg cctgcttgag 10020 g gaccgatc gcgtcgagtg ccttggagst gtaggggtcg aggtcgagga tgacgtcgta 10080 gaagacggtc ttgccgtcct tgcccatgcg ggggtctgcg acacggctga cgtgatcggc 10140 gtcggtgagc gcggtggcga tgtcggcggg tgcggggctg gagcgcaggt tgtcctggga 10200 atggacgacg acggtactgg gggcgatctc gccgggcccg aattcctccc gaatgaggtg 10260 ctgtccgtgc tccgactcgg tggcggcgcg gaagccgctg agggtgttga agctctcctg 10320 gtagccgagc agtcccgcgc tcagtaccac caggagcgcg atcacggccg aggccacctt 10380 cgtgcgacca gacgggggcc gggcggcgat gcggtgccag atgcctgcgc cgcgactgcg 10440 ttcggcggcc ttgtccacgc ccccgggcca gaagacgctc ctgcccagca ggaggaccag 10500 ggcggggatg aaggtgaacg ccaccagcgc catgacggcc acgcccagag cgaggtacgg 10560 tccgaagccg tgaagtgccg gggagacggc cacgagcagg caaacatgg cgagcacgat 10620 ggtcgaggcg ctggcgagga cggactcggc ggtgcggcgc acggcggcct gcatcgcgcg 10680 ggcgcggtct ggctcgtcga gcagggtctc gcggtagcgg gcggtgacga tcagcgcg to 10740 gtccgtgccc accccgaaca gcagcacggt catgatcgag gcggtctggg agctgaccgt 10800 gacgactccg gcgtccgcga gaatcgcgcc gagagtctcc GCCA cgcgca tagccacgcc 10860 cacggcaaga agcggcacga gcgccatcag gggcgagcgg tagatcgcca gcaggatgat 10920 caggacgagc acgacggtgg ccagcagcag gactttgtca. ccgccgctga agaccttcac 10980 ggtgceogtg gcgatcccgg cggggccggt caccgcgacg tcggc GGCC cggcccggtc 11040 ggacg? Gagg gcacgcacct 'cgtcgaccgc attctggaag gactcctccg aggggctgcc 11100 acgatgacca ctccatgggc gctgagcacc gcggtcctgc gagaccaact cggccgcagc 11160 gtcgggagcg gtcaccgtgg agaccacgct cacgacatgg tcgggtcggc tggttccgga 11220 aagggccgag gtgatggcgg cgaccgattg cgtggcgctc ttcgcggcgt cggtgccctt 11280 gccgcggacc acgatgatcg ccggcgtcgc gtcctggccc ggaagcrggg cgcggacgag 11340 atcacgggcc ttcatggagt ccgaggcggc gggcggcagg ttggcggagg cgttgtcctc 11400 GACG ATTCC agggccgggg cgaccccggc gaggaggccc gcgatcagga cccagaaggc 11460 caccaccacg gcggcgcgct tcttcgatcc caggagacat cgcagcagag cgggggagtt 11520 catcggccgc atcgggcagc cttcggcagg aagtacggac agaacttagc gacagggtgt 11580 ctctaagttg cgtcaagcta acacgccccc tcggcctctc gggcgtgggg gtaggttggc 11640 gggagacggc acagcgtccg aggtgaagcg gagaaaatgc ccaagattga agccggcagc 11700 gtccgggagc accgggcgca gcggctcgcg cagctgattg acgcggccga ggagctcctg 11760 gaagagggcg gtgccgaagc cctcacagcc g gagcggttg ccgcgcgagc cgggatcgcc 11820 tctaccgcta cgcaacagca cttcaactcc atcgacgacc tgctcgaact cgtcgtcacc 11880 cgcgasttcc ccgcctggat cgacgcagtg gagcaggcca tcgcggccga gaccacaccc 11940 gccgcecagg ctgccgccta cgtcagggcc aacctcgaac aggcagctcg cggcacccac 12000 ggctggcggg ccgcgctcac gcgcgactcg ctctccccgt cggcgcggga gcgggtgagg 12060 tctcgctaca aatctgcaca cgaggcgctc gcccgggtcg tgcgcgaact ggggcagcca 12120 cagcccgagc tgaccgtggc ggtggtccaa gcagtcgtcg atgcgtgcat ccgcagaatc 12180 gaccaaggcg acgatctgac aaccgcgtcc gactccgcgg ceggagcgac gcgtcgactg 12240 ctcgcggatg acgacttgcc acatcacccg tgacgcaccc cgtccaggcg gctcgcaggc 12300 ccgtcgacag cgaagccccg gcagaacgag ccggatcttg agccgeaccg gagcgtgacg 12360 cagaccgctg gtggctcatg cctcgtctca tccgatcttg ccaccgggcg gccgaccggt 12420 cgcccatcga cagtgcccga ttacgacgtc cacgacccga accagcgcgt tcagtgcgtt 12480 gacgtccgtg gtgcgctcat tggtcacccg gcctctgggg gtcaccagcg cttttagggc 12540 acgagactcg acggtggcgc gtgataccag gcaggcatca tgacctcatg gcgatgacac 12600 tccggcttcc cgacgacctg gaca cgaagc ttacggagcg ggctcgtggg gagggct ca 12660 gcaagcagga acctgccatc ggggccattc gtgatgcccg ggaccgggcc gagctgaagg 12720 tcgatgacgt tccggccggt ctgatggaca gcgatgcgga gattctggac tacctgaagt 12780 gagcggcgtg cgctacctcc agatcgacga gatcctggcc atcgtgcgca cggtcaacgg 12840 tgccgagcac agcgtgcgtg acatgggcct ccttgtgtcg gcgatcgaac ggccccggac 12900 gaacgtcttc ggagccgagc tgtatcccac cctgcacgag aagccgcggc actactgcac 12960 tccgtcgccc gcaatcacgc gctgatcgac ggcaacaagc gcaccgcctg gttcgccatg 13020 cgcgtcttcc tgcggttcaa cggcgccagc gccagtaccg tcccgcccca cgggcgccgg 13080 cccgacggac ccgaggcccg tcacgcgctg ctcaccagca gccctctcct cagcagcgca 13140 ctgggaccgg cgctgctgat cgccctgtcc gccctggggg ttctcgccct ggacacggcg 13200 ttgtgggtct cggtggtcag tgaggtggcg gcgccggccc ggtggggctt cgtgggcggg 13260 ctgcgtgtcg gcgccgggcg tctgggagcc ctgatcgccg gcgtactcaa cgccgtgatc 13320 ggtcttggcg tggtcgctgt caaactcatc gccgggcact gagagggcct gtggtggtgt 13380 tcgcggagcg catacggtgg cagaccggtc ggaatcctcg gcgccgcggc cggagcggtc 13440 ccggcacccc ggegaacagc cgcacgtccc cgtccggtcg ggtcaggtcc gagccgtcag 13500 atccaggtca gtcgccacag gcgcagaagc ccggtgccgt ccaccgcgta ctggccgccg 13560 cccacgtcct ccccggacac cacgaagtcc ttggcctgcc acagcgggac gacgggcacg 13620 tcgcgggcga cgatccgctg aagggcttcg aggtcggctt cggcgtcgct ccggtcggcg 13680 aagcgctgac tgctcgtgat cagccggtcg gcggccttgc tgccgtaccc cgtcgccatg 13740 gtgccgtccg tgccgacgag aggaccgccg aaggtgtcgg gatcggggta gtcggcgacc 13800 cagccgacgg cgtaggcgtc gagctctccc tcggcccagc tcttctggaa ttcgtcccat 13860 tcataccctc tgagggtcac cttgaacagc ccgtcggcct ctagttgctt tttcacctcc 13920 gcagcctcct cgtgggctga tccgcgtccc gccgcgtaac cgtaggtgaa agacagcggg 13980 atttcctcac cggcctcgac gaggaggcgg cgtgcctttt cggcgtcctt gtgagggtag 14040 ttgtcgaaga aggaggtggt gtggcccgtg atgctcgtcg ggatgaggga gtagagcggg 14100 tccacgcctc cgtcgtagac gtcgtaggaa atccggtccc tgtctatcac ccaggccgcc cg 14160 gcctgccgtg cgcctgtc gtgaaacggc ttgccgcggc ggttgttga? gtacaggttc 14220 cgagtctccg cgctctgcgc ctccgtcacg cgaagccccg gatcgctcgg gttcagatcg 14280 gcgagcattt cggggggaag ctgtctgagg gcgacatcga tgcggtggga tatccaggcc 14340 cgggcgagtg agtcgggggt gtcgtagaag tggagttcga tcggccggcc ggtgttctcg 14400 gcggcgccct tgtaccgagg gttgggcgag agggagatct tctcgccctt cgcgtaggag 14460 acgacgccgt acggtccggt cccgtcgatc cggccgtccg agcgcaggga gtccgccggg 14520 tacgtggtcg agtcgacgat cgagcccgcc ccggtcgtca gcttgaaggg gaacgtggcg 14580 tscggtgcgg tcagtcggaa agtgacggtc cggtcgcggg cgtccatcga ctcgatggtg 14640 tccaggaggg acgacggccc cacgtcggaa tctatcttct tgacccgttc gaacgagaac 14700 cggacgtcct tggctgtcat tctgcgtccg ctggagaagg tgatgtcatc ccgcagccgg 14760 catcgatagg tgcgtaggcc ggaatcggtg aaggagcagc tttcggctgc gtcgggaacg 14820 ggctccgcca ctccgggctc cagggtcagc agtgtctgga agacattgct gtacagagtg 14880 gtcgagccgg agtcgtagcc gccggccggg tcgagtgacg tcggcggttc cgtcgtcccg 14940 accttgatgg tggtgccctc ctggtcgtcc gtcgggtaaa gcagcagacc ggctgccagt 15000 gccgtggcga tcaccgtggg tgtgatgacg gacgcacgga tgt gcgcacg aataggtctc 15060 atgaggctcg tcctcgcaag atcgagacga acaggaattt tcgtacccct gggtggagag 15120 tgcgtcggcc aagtatgcgc aggcgtcgct tccttcggag cccgacggca cttccggaac 15180 gaagtcttat gactgacacg gtggaactgc tatgccccgt tcggcgagag ggccgccagg 15240 ggtcggcacc ccctctcagc agccgttccg cctcgtctcc ggtggtcctg cggacccgct 15300 tgcgcgggtc ccgcccacgg tctcactcct cgatgccatt ccctgtgcaa tgtcacctgt 15360 gccatgttcc gtgttgcagg gcgtggccat gccaagtcgg gaggtcgttc gtcttccgtc 15420 aggtggcagt gcggtactcc gtttcccacg tcctctcccc cttcagtcgg ccgtgctccg 15480 cacggccgga tccctcatgg gaggcgctgt gagaaagtca ctggtacggc gaggtccggg 15540 ggcggcgctg ccgctggccc tgaccgtcgc catgagcgtg ggcctgctgt cgcagccggc 15600 cggcgcagcc gggaacaccg ggtccgtcgt gcacgtcgcg gcggacgacc cggagcacgc 15660 gggacccccg cccgtcgcgc agtcccccac cgccgagacg gagcacgtcg cgcagggacg 15720 cacgágggcg tccgagcttc cgcccgtggc cgcgagtaag gacgcgctca aggasgtgta 15780 cggcaagace gcgaaggcge cggtccgtcc ctcgaagtcg acggacaagg cggtcgccgg 15840 caagaccggc aactcccgtg cgcgtgccgc CGCG tgcaac gtctccgact tcaccagccg 15900 gagcggcggc gcgctggtcc agcagatcaa ggcgtccacg accgactgcg tcaacaccct 15960 gttcaacctg accgggaacg acgcctacta cgccttccgt gagtcgcaga tgacctcggt 16020 cgcctacgcc ctgcgcgacg gctcgacgtc ctacccgggc aacgcctcca ccggtatgcc 16080 gcagctcgtg ctctacctgc gcgccggcta ctacgtgcac tactacaaeg ceggcacggt 16140 gggcacctac ggcagcagcc tgcagaccgc gatacgcgcc gggatcgacg ccttcttcgc 16200 cagcccgcac tcccgcgacg tcaacgacgc caacggcgag acgctcgccg aggccgtcac 16260 gctcatcgac agcgccgagg agaacgcccg ctacatccac gtcgtcaagc gactgctggc 16320 ggactacgac tccacctgga actcgtcgtg gtggatgctc aacgcggtca acaacgtgta 16380 cacggtgacc ttccgcggtc accaggtgcc cgcgttcgtg agtgccgtge agtctgaccc 16440 cggccrgatc gacgcgetct acaactccgc gagcggccac ctcgcgctgc tgggaacgga 16500 ccagtcctac ctcacgtcga acgcgggacg tgaactcggc cggttcctgc agcattccgc 16560 actgcgctcc aaggtcagcc ctctggccgg cggcctgctc aactccagct ccatcaaggg 16620 ccggacggcc ccgctgtggg tcggt? TCGC cgagatgacc gactactacg acaaggccaa 16680 ctgctcctac tacggcacct gcgacctcca ggcacaactg gcccgctccg tcctgacggt 16740 tgcagctcca gacctaccca gcatcaccat caaggcgcag cagatgacct cgggcgagct 16800 gtcctccagc tgcagcagcc tgcgcaacca ggacgcctac ttccacaacg tggtcegtga 16860 caacggcccc gtcgcgaacg acaacaacag caccatcgag gtcgtggtct tcgactccag 16920 caccgactac cagacctacg ccggcgcgat gtacgggatc gacaccaaca acggcggcat 16980 gtacctggag gggaatccgt cggcggccgg caaccagccg cgcttcatcg cctacgaggc 17040 cgagtggctg cgtccggact tccagatctg gaacctcaac cacgagtaca cccactacct 17100 cgacggccgc ttcgacatgt acggcgactt caacgccaac atcaccaccc cgaccatctg 17160 gtgggtcgaa ggcttcgccg agtacgtctc ctactcctac cgcggcgtcc cctacaccga 17220 ggccacgacc gaggcggggc gtcgcacgta cgsgctgagc accctgttcg acaccacgta 17280 accacgcgca cagccacgac tctaccgctg gggctacctc gccgtgcggt acatg-CCGA 1734 C aaaccaccgc gccgacatgg acaccgtcct cagccactac cgcgcgggaa actggsacgc 174 00 cgcccgcagc tacctgaccg gcaccatcgg cacccgctac gacaacgact ggtacacctg 17460 gctggcggcc tgcgcggccg gcaactgcgg tggcgggggc accaacccgc ccgggaacca 17520 ggcgcccacc gccgcgttca ccaccgccgt ccagggcctg aacgtcacct tcaccgacca 17580 gtccaccgac gccgacggca ccatcgcctc ccgctcctgg agcttcggcg acggcaccac 17640 ctccacggcc accaaccccg tcaagacgta cgggtcggcc gggtcctaca cggtcaagct 17700 gaccgccacc gacgacaagg gagccaccgc caccgccacg aggacggtca ccgtcggcag 17760 cggcggaggc ggcggcaccg aatgcaacgg gaccgacacc cgggaact gg gccagaactg 17820 ccaacgcggc aaccagtccg ccaccaccgg caactacgcc tacctgtacc tctacgt ccc 17880 ggccggcacc acccagctga agatcaccac ctccggcggg acgggcgacg cggacctgta 17940 ctacagcacc agcggctggc ccggcaccac gagctacacg cagcgggcca cgggagccgg 18000 accctgacca caacaaccac tcaccaaccc gccggccggc tcagcctgca gccaactaca 18060 cgccgtcagc agcttcagcg gcgtcaccgt gagttccgcc tactgaccca cggctccgca 18120 ccaaggcacg accctcacga cggcccgggg cggctctccc cgccccgggc ggcgtccggg 18180 gcggcggcag gggggagacc tccgtcgccc Cggaccgaga acacatcgcc cgcccgcaca 18240 cgggcatccc tacctcccag gaggcagagc gtgaagtcat tacccgcacg caggcgacgc 18300 cgcgccatgt ggtccctcat catgtccgtc ggtctcacct g cgcactc c cacacccgcc 18360 gtcggcagcg gtgaccaggg cacgtcacgg ctcagcgcct cgcaacaggc cgcggccggc 18420 caactcgcag cggaccagca catctccacc caggaggcac agcggcgcgt actgcggcag 18480 gagcggctca ccggcgtcgc aacagcgctg cgtgagcgcc tgggttcccg cttcgcagga 18540 gcctggatcg accagaagca cggcggcagg ctgaccgtcg ccgtcacccg gtcgacggcc 18600 acggccctcg tcgaggcccg gtccgctcag gctcaggcac ccgacacgac caccgtcgt c 18660 gcctgcggca gtcgaccgca actcgaccgc atgtccgcag gactggccca ccgtatcgcc 18720 gcagcgaaca agggcgccgc ccacggcctg cagtccgcgg tggtggtgca ggacaacaag 18780 gttcgtctgg acctgccacg gggcaagacc ctcacccccg cccagcacgc agtcgtggag 18840 TGGG gaagc ggaccctcgg cgatggcctc gaggtcagca tscctccgaa cctacgccca 18900 gcggcggcca cccttctact gtactcgtgc gaccccccgc tgcgctcggg cctggccatc 18960 tacggcacga acgtccgctg ctccagcgcc ttcatggcgt acagcggcag cagctactac 19020 atgatgaccg ccggccactg tgcggaggac agctcgtact gggaggtccc cacctacagc 19080 tacggctacc agggggtcgg tcacgtcgcc gactacacct tcggctacta cggcgactcc 19140 gggtcgacga gcgatcgtca ccccggcttc tg gcagccgc gcggctgggt ctacccctcg 19200 ccaactggga acccgcatca ctacgactac gtcggccagt acgtgtgcaa gcagggctcc 19260 acgaccggct acacctgcgg gcagatcacc gagaccaacg caacggtgtc ctacccaggc 19320 cgcaccctga ccggcatgac ctggtccacc gcatgcgacg ctcccggtga cagcggcagc 19380 ggcgtctacg acggctcaac ggcecacggc ateetcagcg gggggccgaa cagcggatgc 19440 ggcatgatcc acgaaccgat cagccgagca ctggcggacc gcggggtcac gctgctggcc 19500 ggctaagcag cccgggcgga ccgtgagtac gccgccccgg tcacatcacg aggacgtcga 19560 ccgccgcacg cgcggtcggc gtctttcccc gtgctccgct ccgtccgcca cccagcggac 19620 tgggggcggg ggcgtggcac gtcgtgcacg ccgcagcgcg gtggaacccg tcggccgatt 19680 agaccgtacc ggggagcgcc tttccggctc cgttcgtggg acgggcgggt gcgtatgcgc 19740 gcgtcaccca tttctggaag tgcggagcct gcgacagcag ttgccagtgg gcgcgtacgg 19B00 catgatggtg caccacctcg acggccgacg atcccgccgc cctcgaccga cagacgagca 19860 ccacagcgga gatgccgctg tcccccgega ggggtttaac cagtactccg cccaccgggc 19920 gcatggtggg ctggacggcg gccaccccca gacccttggc gatcatcgac tgcagttggt 19980 cgagcatgtg gaactcgtgg gtgac ggcgg gcctgaatcc cgcggcccca caagcgtcgt 20040 agaaggcgcc gggccagccc accccgtcgt ccgcggagac gaaccacgcg tcetccgaca 20100 ggtcggccaa ggacacctcc agccggtgcg ccagtgggtg atcggcaggg gtggccacga 20160 ggttctgata acaccgggac gctcggtggt ccagcttcgg agagtgtcga agaggcagcc 20220 ctgggtagtc gcaacccagg gcgacgtcga gctcgccggc ctctaggaga tcgatgagtt 20280 ctccggtcgc gtacacactg ctgaccgaga cggtcagatc ggggcaggct tcacggagga 20340 cgtcgagcaa ggtgggtacc accggtgtgt tgatggcccc gaggcgaagc cgacgtgtcg 20400 ccccggacga gcggggaggc cgcagccgtg cgagattgtc ggagagcgcc aggatctccc 20460 gggcccggcc gacgacctgg gcgccgtagg cggtgagctc cacgcccgcg ctgctgcgca 20520 ggaagacccc ctcgccgagc agtccctcga tgcggcgcag ttgggtactc atcgccggct 20580 gggtgtatcc gagcgccgea gcageccggc cgacgccccc cgcgtcggct atcgcacaca 20640 gcacgcgcaa gtggcgcagc tcaagttcca cgggggcacc tcgctccggg cgaacagagt 20700 tccattatgc gccaggagga aggcggtggg gaatccggga cggcctgacg ccttcggtcg 20760 accagtagcc cgagggttat ggatgagccg gagcctctgg tatggcctgg ccggttgt c 20820 ccgggtgacc gccgtggaaa tc tcggacct gcgtgttggt ccgcagaggc gactgcggaa 20880 gcctgaagcg caccgccatc gaggagcgac atcatgcctc acacctgcat cagcttcacc 20940 gtcgaagcga ccggggccgc ggttcaccgc gcccgccacc gcgtctccac cgcgctgagc 21000 tggtggggag ggccggtcga ggaagagctc cgcttcagcg cggaactcgt gacctccgag 21060 ctcctcacca acgggctgcg gcasgcgggc gggccsatga ccgtcgagtt gacgctggtg 21120 cacgacatgg tcgtcgtcgc ggtcctcgat gacagccggg agctgccgcg gcctcggcag 21180 acggaggcgg acgacgagtg cgggcgggga tcgaggacct ctcgccctga cagtctgata 21240 cggggagtcg agaccacttc ccgcgggaag cgctgctggg cggttctgcc gctgcggacg 21300 ccacaggagc gggctatcga gtcggctccg gctgaggagg cggaccacgg cttcgaggca 21360 gaccgggaac gctggtcact ggctccccaa ggaagcggac tactggcgag tctgtttccg 21420 gcgatgtgag ttcgtcctcc tcgggcggcc cagcagccga cccagggcag gcgggcgtgc 21480 ctgagggcgt gatgacgctc gtctgacgct ctggccgctt tcaagctgca cagcgagccg 21540 agaaacagcc tttgacctgg ccttttctgc ggctgcctca ggccgacatc tttccgatga 21600 cgcaccacgt ggagtacgtg gcgattctgg agcctgctgg caaggggttc tgacctgcgc 21660 ttttgttctc ctgcg gcggg cgcggcaagc tcgtgcgggg cagttgggtt tcccgaaggc 21720 cggtgctcgt gtgtccggcc ggcgggtggg ctgccttcgt ttcagtgggt gcgagagggc 21780 actcggacgc ctgagccgag atgcggttcg ttcggcacca tggggtccgc aggatgaccc 21840 ggtcagcgac cgctggcacc tgtggaagaa cctttgcgac aaggccctgg ccgaggttcg 21900 ctcccacagc gcctgctggs ccacagcgaa cacaccccgc ccggccggcg tccatgagca 21960 gaccacccgc gaacgttggc atcagctcca cgacctcctc GGCA = gggtg tcggcttgct 22020 cgaatscgcc cgccgcctga acctgtccct caacaccgtc aagcgctacc cgcgcacccg 22080 cgatcctgaa gccctgcgcc ccgtgaagca gctgtttsgc gaggtccagg agcagggctg 22140 caccggcagc ttcaccctgc tctaccgcag cacccagggc cgggcagaag gcgaccggcc 22200 cgtcggaggg tcgcggcttg acgctcaccg tatccatcac tggaacggcg acgtctgatc 22260 ccgtctgccc ggggcttggg tcccggctgc ggcccgtagg cccggctcac cccagcaccc 22320 atcactgttc gagagtgatt acctctccgc cggacacatg gaaatctgca tcggctggag 22380 tagacattgg gcagcagtgt ggttatgttt ctcctgtaac ccagaaggac cgcagggccc 22440 ggcagagacg aactgccggg cagcagcacc cgcagttgca ggacggcgcg gtggtggagt 22500 gtcgaagc ca ggatggtgca ggacggcgac gggactgacg accggaccgg gcggcccgca 22560 gtggtcaggg gccgccaccg cagtgcagca cccagcagcg aagtcagtga gcggtacctc 22620 ggtgaaggcg tcggctgc? g acgcgcgcgc cgggaggttc ggcagtggtg gttccaagcc 22680 agagcagacg caggacgggc aacggggceg actgtcggac agtggcgctg tcacaggtca 22740 cgtgtcacca ctgagaggtt gcagtagagc agtaccagag gaaagaacgg aggaaccaag 22800 cgccatcagg accgcccggg cgcagttttg ggcccgggca ccgcaggaca tcgatagtga 22860 ggtggtcccc ggtcaagaaa ccgcgstccc cgcgcccccg gcagcaggca ggtcgggtcc 22920 gcggecacag aaggccggtg cagtatcagg gccggcagat ggtgtaggag ttccttcggg 22980 gccctggcgc cgcatggcac cagggcccct ccatgcgttc cgcagagagg tgcagatgac 23040 ascagacgat tcgtacggcc gtctcgacga cgacgattac cccgcctaca ccatggggcg 23100 ggcggccgag atgctcggta cgacccccgc tttcctgcgg gccgtcggag aagcccggct 23160 gatcacgccg ctccgctcgg agggcggcca cc ccgctac tcccgctacc agttgcgcat 23220 cgcggoccgc gcccgcgaac tcgtcgacca gggcactccc gtcgaggcgg cctgccgcat 23280 cgtcarcctg gaagaccagc tccaagaagc gcggcgtatc aacgaggaac tgcagaggcg 23340 cccggccgge ctggtggaca aggccgaggg ctgaggccgc atctgccggc cggtcctgtg 23400 agggctcgcc tgccaagacg ggaagccctt gccgcaacga gaagaggcaa ctgtccgcac 23460 cgacgtgctg ggcccggtcc tggctasgac tcccgtcttc ttgccgg = gc gacgcggccg 23520 tggacgcgga accggacggc agtgtcgccg ggcgcggacc gcggggcgca cgtcgatggc 23580 gacaggaccg gcgaaggtgt attcgtgttc gscggtgtga cggcgcacct ggccggcgag 23640 ggcggcggcg caggtgtcac agggacatcg gttccgactt ccaccacccg tccgggttcc 23700 accagcgtgt catccacctg atccaggstg ccgcggtagg tgctcgacgt cggggg gta 23760 cgggggcagt tgtaccgttc cgccgcgagg agtgacccga ttgaccaccg gcctgtggcg 23820 ctcaggaacg ggctggactg tcgcagtccg ggccaactca agcccgacca tgaggccgac 23880 cacggcgccg cgcgaccccg accacagcta cacgcgtggc atgaccaagg cggcacatgc 23940 ttcgaacgag ccatctcatg tgtgccggta tgaacgtgat cgacgtcccc ggcactctgg 24000 tgcggacgca agccgtctgg ggcgccaccc acgactggct cgccgccccg cccccgcggc 24060 gccaccgtcc gtcccgcccc gcgtcgtcgc ccgtgtggcg tcatgacggc gacagacttc 24120 ctcgcgtatg ggccgaccat acggccaacg ccagaggtaa agcgctgtcc atggtgagtt 24180 DC ctgaaeag aagggctggc gggacctcct ttccaagacc gtgctgcagg agtccgtcag 24240 agcgcaggta atcccgtgct gtccgcgacc cagggctgtc ctccgtctgg ccgagggtcc 24300 tcgtcttctg ggcgacatcc ctttagcgtg ggcggtagcc gccgaaggqa ggcgccatgt 24360 cggacgaatt gacgggcccg ttgggaacgg caatgcggga ggtcacgttt ccggaccggt 24420 ctcgcsggat catcttggtg cgggctggaa caccgcaggc cgaggccgag gcaatggccg 24480 cccgtatgtg ggccgagatg ccggaaggct gacgtgcccg aacgcagaca acccgtaccg 24540 tcctcacacg cattcccctg agccgtcggc catggaacgg aaccagccgt acgaaccccg 24600 saggcgccgt tgcggtctct gcggcgaggc cggggccacg cagggcgasg aggccgcgcc 24660 gcgctctgcc gcctggcgcg gctgccggct gttcacgaga acaccgaggg aggagtcgcc 24720 cgcctcttgc ccggcgcgtt gccgggtgga gagcaggtgg tgaaggactg gctcgctgaa 24780 ggcsqccgag gcgacctcgt cggccggcct gaacggcttt cactgcccca gcggcggcag 24840 gccgccgaca caggcatgct ttgccatctc cctcgctgtc tactgacccc agcagcagga 24900 tccagtacgg cgtcgcggcg ctgccgcctc actcgcgcat cgatcgggga atgcggcatg 24960 tggcgagggc ccggccggcg tgccggccgg gccctcacac tgttttggtg ccggcgcgtt 25O20 tgtcctgtcg gtcagacgga caggtggggg gcgccgagca tggcggaacc ccgctgcaac 25080 ggaccgtcgc c gcgcgcggg ggcggcctcg ggaagggtgc ggcaggtgsa sceeagctcg 25140 gccat gccc ttaggat etc gccggtgctg aagtcgcggc ggccctggcg ggtgatgacc 25200 tggccgacct gcttggcggg gtagtggcgt cgtccgatga tcacggactc gccggtgacc 25260 ggttcgggtt tgacgccctt catcgattcc agcacgccgc tcttggtcag gtcgaacggg 25320 aagcgggcaa tgacacagcg catgatgcct cacaggcagg agagttacgg ggccggccgc 25380 cgtctggcgg ttcagcggga gagagcgagg acgcccaggg cgctgccgtg ttcgtcgacc 25440 acgggc ^ cca gcccgagccg tccgaagggc accgcgtcct cggcttcctc cctcgtggcc 25500 gacggtgaga cgaagggctc gctgtcgtcg gtgatgtcac cgaggsggag ccggtcggtg 25560 tatcgggagc rgtcccggac ggcggtgagc cgggcctggg tgaccaggcc gacgcaccgc 25620 gcatcctcgt cgcagacgac cagacgctcg gcacgggcgg cggccatcac ggacagcgcc 25680 acctcgacgg tcatgtcgca ccagacctgt ggcccggcgg cgtccatga c gtcggccac 25740 gtgccgcgca atgggagagc gcctacggag cgatcctgca actgtcctgg cgtcaagggg 25B00 tgccccctgc gcagacgggc ggggttcctg atcaggacgg tcctaggcgc ccgcgccagc 25S60 cgt ggacttg agtgcggggg tacgccgcgt cgccgaggcg GGGC gcgtc ggccgcgtga 25920 ggtggcgccg CGCT tcttgg gg gttcagt cgccggggcg gcgatgacca ccgggacgcc 25980 ggtcggggcc tgggctccgg tgacccggct gagggcctcg tcgcccgggc tgacctgsgt 26040 ggtctgcggc cggatcccgg cttccgacat gagacggacc atgccgcggc gctggttcgg 26100 ggtgacgagc gtgacgacgc tgccggactc gccggcgcgg gccgtgoggc cgccccggcg 26160 gaggcagtcc tt gtggccgg tcggcgggtc gacgttgacg acgaggtcga g? ctgtcgac 26220 gtggattccg cgtgccgcga cgttygtcgc caccagcacg gtgacgtgcc cggtcttgaa 26280 ctgcgccaga gtgcgggtgc gctgcggctg ggacttgccg ccgtgcaggg cggcggcccg 26340 taccccgctg ttgagcaggt cccgggtcag tctgtcgacg gcgtgcttgg tgtcgaggaa 26400 catgatcacg 'cggccgtcgc gtgcggcgat ctcggtggtg gccgcgtgct tgccggcgcc 26460 gtggasatgg agtacgtggt gctccatcgt ggtgacggcg ccggccgagg gcccgacgge 26520 gtgcscgacg gggtcgct ga ggtagcggcg tacgagcagg tcgacgttcz gcccgagggc 26580 ggcggagaac agcatgcgot ggccttcggg acgcacctgg tcgagcagtg cggtgacctg 26640 cggcatgaag cccatatcgg ccatctggtc ggcctcgtc g aggacggcga cggagacctg 26700 gttcaaccgg cagtcgccgc ggtcgatgag gtccttgaga cgtcccggag tggcgacgac 26760 ccaccacgca gacctcggcg gcgccgacgc ctgcctgccg atcgacatcc cgcccaccac 26820 cgcagcetca cgtggccagc cagagcgggc gtacggggtg agcgcgtcgg tgacctgctg 26880 cgcgtcggta cgccagctca cgaggaccag ccccagcggc tgccgaggct cggcccgccg 26940 cgggccagca gccggccgta gagccaggcc gaaggcgagg gtctttccgg aaccggtgcg 27000 cccgcggccc atgatgtcgc ggccggcgag ggagttcggc agggtcgcgg cctggatcgg 27060 gaacggcasg gtcacccctt gttggccgag cgcggccagc agttccccgg gcatgtcgag 27120 atcggcgaag ccctccgcag cgggaagcgc gggggtgatc gtccggggga gggcgaactc 27180 cccctgaacg gcgccgggcc ggcggccgta accgccggag cggctgggtc cggccggccg 27240 gcgcggcgcc ggcgaaccga agcggctgcc gccctttccg gagtcggcac cgccatgacg 27300 ggtgcgagcg aagcggtcgt tcgtgcgtgt gcggttcata cggaaccttc ctcgatgcgg 27360 caracaccaa ggaatttccg aagcaatgag cagcacggag aatcgcaaga atggaccggt 27420 gggccttgcc agcggatctg gccgacagaa aatctgtgcg gcacgtgcgc tggaatgatt 27480 qggggtgctg tgggctcgat attcgaagcg aka actgcac tgtagctatg aaggatgcgg 27540 ctgcaccttc gaaggacgat ccgtgtgcgg taaacacacg ctgtccggag cgtcgtccgc 27600 aggcga = atc actgcgggaa acgcatgtag ctggggcccg caccccgaag gatgcgggcc 27660 gtacgtgaca ccagctacaa gtcggcgtca ggcggqaacg atgttctcgg ccgtcgggcc 27720 cttctggccc tgcgcgatgt cgaagttcac cttctggcct tcgagcagct cgcggaagcc 27780 czgggcggcg atgttcgagt agtgggcgaa cacatcagcg ccgccaccgt cctgctcgat 27840 gaagccgaag cccttttccg cttcacggta cgttgaacca ccagcagcca tgtcatttct 27900 cctccggggc agtcgtacgg gatccgcacc gcgcggacct cgtgtcgccg caatgatcac 27960 cccgcccgga aaaagaccgg agatgtaaaa gtgcttccag gggtactgag cccgaccgga 28020 tttcgggaac gcacctgaaa cacaactgca actgacatcg acagtagcac gccacagcag 28080 ccaccgtgcg gtgaagaacg ccaccttgct tattgcggca gagaatctat ccgcacgctc 28140 cgatgaaaac tcaaaccgcg cgcacagata ttgaccttcg cgcgacgcca tatatcgcat 23200 gccgcgcccg cgtgatccgg tcccccacea cgctctccgc tactgcacgg gtcgcaccgc 28260 cgcgggggca gacaggtccg gccatgasgc cggccatgct cggggcgcag cggacgcctg 28220 ccggtcgggt gtacgtctcg cgcgcg gcga gcactgcggg ggaggggccg gttgccagac 28380 gtctcgcctg gcaaccggct gtcggctcgg gctggttggt cagccgtggc aggtgatgtg 28440 gttccgcgcg cccgcttccg tgaacgcgcc gcagccccgg ctgccttcta ccaggccgac 285OC cctcaggagg cgtgacccgg ggaagccgag gatcagcggt agtcgtcagg ggaggcttcc 28560 ttgccgccgt aggtgacgtc ctcgaagtat gcccaggcat ccggccggct gccgtccacg 28620 tccgtcaccc cgtatgccct ggccagttcc ccgctggagg tggacttgcc gttccaccgc 28680 ttcgcgcggt ctgggtcggc ggccagcgec gcgaccgtac gggccaggta gtgcggg ac 26740 tccgcgatcg cgaacgtcgg ctcttgggcg atcgcgtcac gccagttctc ctcactcaca 28800 ccgaagcggg agagcatctg ctccgaacgc aggaagcccg gggacaccgc gaccgccgtg 28860 ccctcgtsct ccgccagctc ctgagccagc ccgaacgcga ggcggatcgg ggcgttcttc 28920 gccaggtcgt agtagatgtt ctcgcg? tag cggcggt.tgg agtgcgcggt accgtcggtg 28980 acctccacat gcagcggcgc gtcggagcgg atcagcagcg gaagcagcag cgccgccgtg 29040 atcacgtgcg agcgcgcgcc cagctccagg atccgcaggc cgtcggcgag cggtgtctcc 29100 caqcccttct tcccgaacac cgaggtggcc agaaggtgct cgccgcccca caggtcgttg 29160 acgagaatgt cgagccgc c gtactcccgg tcgatccgct cgacgagggc gcggacctgg 29220 gcttcgtcga gatggtcggt gggaactgcg attccggtgc cgcccgctgc ggtgacgagt 29280 tcggcggtct cctcgatggt ctcggccgtc cggccgacct cgctggcccg ggcccgggtg 29340 gttcsgccsg tcacatacac ggtagcgecg gcccgcccca gttccacagc ctgagctcgt 29400 cccgccccgc gggtagcgcc cgccacgagg gcgatccgtc ctgcca cgg acccttcgga 29460 ccggcccgct cggtgttctc agtggtctgc ctggtgatgt cctcgctgct catgtcatcc 29520 atcgttcacg ctaaaaccga cagaacacgt caccttttat ccgcgcatca gtggggggta 29580 tcccggccat agcgccaact ac tcctcgc actgagcgtt ttcagcgtgg gccaccgatc 29640 gggtgacgcc ggtcaggtcg gggtagqggc cgcaacgcac aaggctcgcg tgcacgacat 29700 ggccaccgcg cgcatgatcc cccagcggga gcccagccgt ccccggcagc cccagccgct 29760 gagaccagcc cacccgggác acccggtccg acaccgcaca cgatcaagta gtcaacctcc 29S2C agacgcgttc agcagcccac atcccaggag ccgtctaccg tcccaggaac ccctgctcer 29B80 ggaccatcgg gctcggcacc gggagtgcac agttgatcag taactggcaa cgagctcgtg 29540 cacggtaagc ggtgaggtgt cgaggtccag atgggcggcg gcggtggtgc ccccagcggt 30000 cggccgacc g gcatgccgag cgggcagccc accggtgtgc cgagcggcgg acccggcggc 30060 ggcacgggca tgggcggcac ccccaccccg cagcacctga agtcggtcag gaccggccgc 30120 gtgaogggct tcgggtcaga cstgtgcggg gaacagcagg cagtcgtccg ggcggatgat 30180 caggttgatc tcgccgtccg tgtgccggac ggggctctcg gcatggacgc gcacgtcgcc 30240 tcgtactcga gatcctgags atcgcgctcc ggtgtacgag cactgctcga tcctcgcccg 30300 gagcacgttg acggcaccgt cgtgcggggc gtcggcgcgg tcggtgagcg tgatgcgttc 30360 cgagcgcagg cccacggtgg cggacgaccc cgcggagcag gcgccggcca ccctcaagcg 30420 ctgaccggtc tcacccagtt cgacctgtac ggctccgccc tcggtggcgc cgacgcgccc 30480 ctccaggagg ttgcagcggc cgatgaagcc ggcgacctcg ggagtggcgg gagtctcgta 30540 ggtgtgccca gatctcggtc cctgctggag gtgtccgtgc atgaacacgg cgatgcggtc 30600 atggcctcga ggacagggac cctggccgtg ggtgacgtac acggtggtga tgccgacctc 30660 ccgcrggagg tccttgagcc agacgcgggc ctggtcgcgc atcttcgcgt ccaggtcgga 30720 gagcggttcg tccaggagca gcacgccggg ggagtagacg atgcctcggg cgagggcgac 30780 gcgctgctgc tgtccgccgg agagctggtg ggggtagcgg tcgcgcaggt 30840 gac gasccaxgtc cttggtg aggacgccgt cgatgaggcg ccgttgctcg ccctcggcga ccttgcggag 30S00 cttcagcggc agtgcgaggt tgtcggcgac ggtcatgtgt ggccagagcg cgtacgactg 30960 gaagaccagg ccgagattgc ggccttcggg gggcaccgtg ctgcgccggg tgccgtcgaa 31020 gaagacctgg tcgccgacac ggatggtgcc cgagtcgggg gtctccagac ccgcgacgca 31080 cgaceaggtg gtggacttgc cgcagcccga cgggccgagc agagtgaaga accccccgtc 3114C cgcgacggtg aagttgacgt cctccaggac cgcggtcccg tggaaggact tcttgatqrt 31200 ctcqacgacc agctcaggca tgcctcttcc ccttcaggag gagaccggcg aggccggcga 31260 cgacggcggt gacggcgatc tggagggtgg cgagggcggc cacggagccg gtctcaccct 31320 gggccoacag atcgatggcg tgacctgtga gtggtgccga gcgacgaaca cccggctccg 31380 tggcgggggc gtactcgcgg atcatctggg tccagatgag caggaacsag gcgagcatcg 31440 cgggcacgag gagacggagc atgatccggg acaccgtgcg ccáccagtcg gcgccggcga 31500 cgcgtgcggc gttgtcgagt tcggctccga gctgcatggt cgccggggag atcgcgccgt 31560 acgccgacgg gagtgcccgg atgccgaagg cgatgatcag cgcgaagagc gtgccgcgca 31620 ccgcgtcgcc gccgggtatc caggtgaagg cccagaacag gccgatgccg ACGA tcaggc 31680 ccgggaccgc gtgcggtgac tgcgctgtcg tctccaggag acgggcgaag cggaagtcgg 31740 agcggcgtgc cacgaggacg accaccgtgc cgaacagggt cacggccacc gcccccacga 31800 aggccacggt gatgctgttg acgatcgact cggtgtaggg ggcgtagtcg aagatcagac 31960 ggaagttgtc cagggtgagc aggccgaacg ggttcaccag cggagtgagc agcgaggtga 31920 acgcgcgcag gatgagsgcg agcatcggca gcagtgcgcc gaagacgacg tacagaccga 31980 cgaaggcgaa gcccagccac ttccaggcac cgatgtcgag caggtcggag cgggtcgcct 32040 tgccgcgcac cgacacgaac cgctgggcgt gccccagcag ccgcgtctgg aacacgacca 32100 gggcgatggt ggcgagcagc atgaaggtgg acgccgcgcc cagcaggccg tagtccggat 32160 tgatcgag ^ c gatgccctgc tcgtagagga agttggagaa gagggtgatg ccggcgggct 32220 cgcccaggat gagcgggatg gacagggtct cgatcgccgt gccgaagatc agcagacccg 32280 cgtagagcat cggcgggcgc agcatcggca ccacgaccga gcgcaggacg cgcagaggcc 32340 •• ccgcgccgac gctgc GGCC gcgttctcca gagaggtgtc ggaggcggcc agcgcgttgg 32400 cgcagaacag gtaggcgatg gggacctggg cgacggcctc gacgaacgcc ataccgggca 32460 gtgagcacag gctccagggc acccagccga agccctcgcg caccgcgccg gtcaggaagc 32520 cggccgggcc gtagacgacg atccacccga aggccaggac gagcggggag atgtagatgg 32580 gccagcgcag cacctgcccg aacaggcggg cggcggggaa gcgggtgcgc tccagcagaa 32640 tcgccatcgg caccgcgatg gcgagcgcga acacggtcgt caggacggcg aagaggaggg 32700 CCGT aggac gatcgaaccg aagcccgccg acgtgaacag gtgggtgtag ttcgagaggg 32760 tgaaggcgcc gccggccgcg tacaggggct ggttgcggac cgaccggcag aggatcggta 32820 cgacgggggc gaggacgagc acggcggtga cgaggaacgt cagccagtgg atggtgacct 32880 cacgtccggc gccgaacagg cgccggtact ggggcgtgcc cagctcgc or gcgcgeggga 32S40 tgcgggacgg cgcgggtggc gccgggggtg tctggatggc catgacgact ccgcacgaac 33000 • • ggggtgggga caggggcgtt gggcgggcgg gggcggctca gccggccgcc ttctcccagc 33060 gcgcgacgta cgcctcccgc acgcgctccg gcacccgcac gggccggcac agatggacgc 33120 ggtccgcgcc gagcctgcgc cgcatgtcct gcagactgtc catggcgtcc tggcgcacgt 33180 ccggccggta cggcaccagg ccgccctcgg cgaccgccgc ctgcccttcg gcggagagca 33240 ggaagtccag gaagagacgg gccgcgttcg ggtgcggggc ggtcttcacg acggacagcg 33300 cgcgcggcat gacgacggtg ccctccgcgt agtagctcca ccccagcagt cccccgctgt 33360 gctcggcggc gggtatcgcg acgccatcac gtacggcagg atcccgccgt gccgcaggta 33420 ggccagttcc tggcgcgagt ggaggcgcag cctgagacgg accgtggcgc ggggtgcgtc 33480 gggccggacg agggacaggg cgacggggtt cgtgccgacg cacaggtcgg cgaggccgtc 33540 gaaggrgaat tcctcctctc cggtgaaggc gtgggccgat gcggtgtcgc cctcctcgaa 33600 ccccaggggc agtacaccca tgccgatcag gttgttgcgg tggatgcgct cgaaggactc 33660 ggctatcacc gcccgcactc ccagcagcgc ctgtgccttg gcggcccagt cgcggctgga 33720 gccggcgccg tagttgcggc ccgcgaccac gacgagatcg tggcccqcgg cgcggtaggt 33780 cgccgcggct -tcgtggacgg gccccatccg cagttgcgt g ccccgatggc c ccctgcgc 33840 atggacgatg cggccgggtc cctccgaggg cctggccgcc gggtcgttcc tgacccgagg 33900 •• cgcc atcag gacgacgccg tgcaacggac gcgaggacag cgtcagcttc gtccgcggca 33960 acagcgacga ccccggtgac ttccgatgac gcgcacgcco ccgccgcccg aacccgagct 34020 gaccgtcgac cgcgccgcct gctctgggtc accctcccgc tccgcctgcg agatcagatc 34080 gccgacgcgc cgccgggcac cgtcgtccac gtcgtcgcca ccgacccccg cggcaccgct 34140 cgaccrgccc acctggtgcc acatgacagg tcacacctgt ctcggcacgc ccccggcgaa 34200 cggccggtgt acgccccgaa gctcaccgcc gacgcgcgsg ccacccgccc ggacgcaccc 34260 tggc = cccgc tccggcggcg gcaggagcag ccccggaacc ggtgacgcac ctcgtcggcc 34320 ggccgtttcg agcggaccgc ggacgcggaa cgtcacggcg tccggaaacc ccggaaggtg 34380 accggcccgc gtgtcttgaa gccgagccgt ccgtacaagg cgatcgcgcc ggcgttcgcc 34440 tcggccacgt gcaggaaggg acgatcaccg cgcgccgaga tgcgcccggt gagagcgcgg 34500 acgaggcggg cggcataacc ccgcccgcgc gcctcgggag cggcacagac ggcgctgatc 34560 tcggtccagc ccggaggacg caggcgttcc ccggccatcg ccaccsgggt gccgtcgacc 34620 cggacaccca ggtaggtgcc gagttcatgg gtacggggcc agaacggccc cggctcggtc 34680 cgcgcggega gatccagcat ctcaggcacg ctgtccgcgc ccagcccgac cacgtcggtg 34740 tcggacgcgg agcgagrtcg gccggggcgg ccgtcgccgg gccaggtcat ctgacggccc 34800 tcaagactga aaaccggctc ccaacccggc ggcggaacgg ecggggagct gaacatgtc? 34860 gcgaaggcgc cgggaccgag taggccggcc aggtcggccc agtcctccgc gtccgggtcg 3920 acggacacgg aggagaaggt cgccacgtcg? Tgagatagg tggctgctcg accgaaccgt 34980 cgggcgagat gagcgtgccg accactgagc gactgaccta ccgggtcgtc gagtgcgggg 35040 tcgtcgtcgt tcatcatcgt gccgtttcct tcctggtgag cgcggcggtc gaagggtggc 35100 cgcggtaggc gaaaagtcgg cggcggggcc cgtggcccga tagtc? TagC ccttgtcacc 35160 gtgcagtttg ccgggtcgcc tgaggacttc cggctggagg ccaatgccaa agcgccctcg 35220 tgccggcgga ggcacgcctt ctgacgtgcc tccaccggca CCactcagtt caggcagatt 35280 gagcttgagc gcagcgc gat cga aatgca cgccggaagt cgagcgcct c t gcggcgact 35340 cctcgt GTCT ggtgagagca gtcctgcctt gtcgagtgat gcggcgttcg gaccgtcacc 35400 ccggcgaagg ccaggacctg tcccacggag tggctcatcc acctccccct cctcggccca 35460 •• cagcttcagg cccgacgcag ggggaggggc gactcggaac ccggcgtccc gctcgcgaag 35520 cctgttcgaa gtcggtcaga gtggaacgcc ttgatgaagc agtcccgggg tcgggcgacg 35580 gcgaagagga tqcaccccac gagggactgc gcggtgaggg cgtcc CGGC ttcgcgtgaa 35640 gtggtcgccc actcctcgga gagcgggtcg gcgttgtcga agtcgggcgg gtagagcgag 35700 atcacccgga ctccttgggc gcgeaggcgc ttggagagga tttcgatgaa ccctgcctgg 35760 gcgctcctgg ccgcgtagaa ggcgtcgtgt gcgtccgagc ggtggcggcc cggtgttccg 35820 caggcggaga ccatcgccac gacgtcgggt gtgtccgagt tgagc = GGAG ggggaggaaa 35880 ctcct cgtgg tcaggaccgt gccggtggct ccggaggcga tggtgtccac gacgtcggcg 35940 tcggttgccg acagcaggtc cggcccggtg aggtagcggg agccgtc gtt gacgagt acg 36000 tcgacgcggt cggtgtgttc cgcgacgccg gaggcgaagt cgcggatcga ggcaggatcc 36060 gtcaggtcgc aggcgaaggc gtgcacccgc tggtgtccgc ggtcgcgcat cccgtcgcgg 36120 • • acccgttggg cggcggcgag ccggcgtgcc gagaggaaga cctccgcgcc gaggtccgcg 36180 aggcggatgg ccagggttcg tccgaagtcc cggccggcgg ccgtgatgac gacgcggtgg 36240 ttgtcccatc tcatggtgtc gttccccagt cgccgtttcg tggatcgggt ggtgccgtgc 36300 accgcgtctc tacgctatcg gtcatggtcg ctcacgaacg gtcgttcacg gtcaatgatg 36360 atgttgaggt gcccaacccc ggtgcggacg aggtctggac cgtcggcgcg gtcatcctca 36420 atcgggaagg tcgtgccttt gcccagaagc ggagccggga ccgtcgcctg ttccccgggg 36480 cctgggacat cgtgggcggt catgtcgagg agggcgagac gcttctgcag gcccccgcgc 36540 • • gcgaagtcga ggaggagacc ggctggcgcc tgacccgtgt gcggcggctc ctcggcacca 36600 cgacctggac gggggacgac ggcggcggcc tgcgtcacga ggccgactac ctggtcgagg 36660 tggacggcga cctggaccac ccgaggctgg aatggtccaa gcactccgcc tacgactggt 36720 tcggccccgg cgatctcacc cgcctcaagg agaaccgcgg accaggggag tacccgatcc 36780 acgacctcat agccggtgcc gttgccgact cgcctttcga cttgctccgg gcggacgccc 36840 tcaccagccc ggaccggctg cgcgagctct acccgcagcc gaacccgaac t cgctgcgca 36900 aggagaccga ccgcctgacc gaggagaccc gggcgctgat cggctgt TCG tcactggtgt 36960 tcatcggcag cgcggaccge gagggccggg cggacgtgac gccacgtggc ggcccggccg 37020 ggttcgtctc ggtgctggac gagcagaccc tggtgatccc cgacgcgacc gccaacaaac 3708O ggctcgacac cctgcacaac gtgctggaga ccggacgcct ggggccgccc ttcccc? aka 37140 ccggccgccc gaccacgctg cggatcaacg gacgcgcctg tgtttcggcc cgcccggagc 37200 tgctcgcccg cctcactccc gtcggaaagc cgccggtcac cgcgctggtg gtgcaggtcg 37260 agcaggtgca tccgcactgc ccgaagtcac tgatgcgcgc cgacgcctgg cgacccgagc 37320 agtggatgcc cgccgacgcc CAGCC agca gcgccgag gacccttccg gt cagctgaacc 37380 tgcccggcct gaccctggac cggatcgagg atgccgaacg ggagtcgctg cgcctgcggt 37440 acgaatgacg acgagt CGAT gagcgccgat gagccgatga gacccgaegg gatccgacgg 37500 gccggcgccc gcggcgagca gaccggtcgc gaaggtcacc gcccgcargg cggcgaccct 375¿0 cgcgacggcc agtactgtcc ggtcaggtgc gggtccagcg ttggttgccg ccgccggagc 37620 aggtgtacag ctggatcagg gtgccgttgg ccgtgscgtt cccgacggcg tcgaggcaga 37680 ggccggactg gacgccgacg acggacccgt cggagttgag gcgccactrc tggttgtcgc 37740 cgccccagca gctgtagatc tggaccttgg agccgttgcc ggtgcctgcg gcgtccaggc 37800 acttgtcgcc gtagaccctg agctcgcccg cgtcagtggc ggcccactgc tggttggtgc 37860 cgctgtggca gtcccacagc tggagctggg tgccgtcgga ggtgctggcg tcgggcacgt 37920 cgaggcagcg gcccgaaccg acgcccttga tctgtccccc gtccgcgggg ggctccgagg 37980 agtcgccgcc gttgagtgcg tcgaggacgg cggtgtacgc ggccttctrg ctgccgtcgt 38040 tgctgaacag caacggcgtc tgctccgacc gccaggagtc gctgtcgcgc acaccccaga 38100 • • cggcgacgcc gaggcagcgc gagacggcca ggcagtcgtt ggtcacgttg gcgtaggccg 38160 aggccggggc gccctggatg tccagctcgg tgatggccac gtcgacgccg agggcggcga 38220 agttctgcag tgtggtgcgg aagttgctgt tgtaggggct gccgctgtcg aagtgcgact 38280 ggaagccgac gcagtcgatc ggcacgccgc gctgcttgaa gtcccgcacc atgttgta to 38340 tggcctgggt cttggcccag gtccagctct cgacgttgta gtcgttgtag cagagcttgg 38400 cggacgggtc ggcggcgcgc gcggtgcgga aggcgacctc gatccactcg ttgccgctqc 38460 gttgcaggtt ggagtcccgc cgcgctcccg aactgccgtc ggcgaaggcc ccgttcacga 38520 cgccccactg gacgatcttg cccttgtagt gggccatcac gccgttgatg tggtcgatca 38580 tcgcctggcg cagcgcgctq ccgctgaggc tctgcatcca gccgggctcc cgggagtgcc 38640 aggccagggt gtggccgcgc acccgcttgc cgttctgcac cgcccagctg tagacgcggt 38700 38734 CCGG cggcggagct gaacttgaac tggccccgct < 210 > 31 < 211 > 3331 < 212 > DNA < 213 > Unknown < 220 > < 223 > Description of the Unknown Body: Unknown < 400 > 31 tcggaccccc ccacacaaca tagatagagg atatccgcct gggttcacaa tgaagc tact 60 ggtggttctc accaccctcg tgggctttag ctcagcacta agtttcgg gt .c = atcacag 120 accagtatta ggcttcaatt cacagtatat gctgggagga ctaagacttt tctgta cgcc 180 tgccatggtt tatgatccat gggcatgtgg ttgcgtttcg gcatggagca gtgcaggtct 240 ttacggtgtc ggagggggcg gaggcgcctg gggagctggc ggtgctggag gagccgacgg 300 cggacgcggc ggcggcggtg gagattggga atatgactat gatgacgaca gcgatgacga 360 tgatgaatgg gactgggatg atgacggtgg aatgggagct ggcgccggag 420 g ggtgctgg tggtggtgcc ggaggtggtg ctggtgctgg tgctggagca ggcgsaggag caggagcagg 480 tgctggactc ggacttggat tgggcggagg tc cggaggt ggacttggcg gacttggagg 540 ccttggcgga ctcggcggtg gagacgattt atttgattta gatttcgatg atcttggtgc 600 • • agctcttgcc ctcggtggag ctggtggagc tggaggtgct gctgctgctg ctgcagctgc 660 cgccgctgcc gccgggggtg gagttggtgg agctgctgcc gcagccgcag ccgctgctgc 720 cgctgcagga ggaggcgcag gtagacttgg aggagctgct gctgcagccg cagccgctgc 780 tgccgctgca ggaggcgcag gtggacttgg aggactcggt ggcggacttg gaggactcgg 840 tggcggactt ggaggcctcg gaggtctcgg tggcctcgga ggatatggag gatctgctgc 900 tgccgctgct gctgct CGCG ccgctgctgc cggaggtgga ggactcggtg gtgtt ggttt 960 cgaggaggta ctacggtgga gacgcggtcg aggaagagga ggccgcagac gtgctgctgc 1020 tgccgctgct gcagctgccg ccgcagccgc tggtggtggc ggaggaggtg gaggcggtgg 1080 aggaggaggc ggaggcgctg gcgccgccgc tgccgctgca gccgctgctg carct gcttc 1140 ctaga agctt caaatgagtg gtataaggga cgcattagga gacattaaag accttctcag 1200 gcctctgcaa gagtaatgga taaagcatca aagcctctgc gcagtagcaa gcacaaaatc 1260 t caaattgac gatttgaagg atgccttaaa ggatcttgca ggtctattga aaagctcagc 1320 atctgcttca gcatctgcat ctgcatcagc ttcagctgga ggtggaggcg gtggtggtaa 1380 cggaggtggt aacggaggag gaggcggcgg tggagctgga gctccagctg c ? Tgctct CGC 1440 tgctgcagga gccggaggtg gacttggagg tggaggcgga ggcggagcct tagccgctgc 1500 actagctgct gctggtgcag gtggaggagg ttttggtgga cttggaggac taggcggc ct 1560 pg * 5g ga tctgccgcag ctgctgcagc cgctgccgct gctgcaccag gtggcggagg 1620 AAG &? CAET t agaagggctt tgagaagaca aatgcgtgga ggtggacccg ctgctgccgc 168C tsctgccgcrt gcrtgcagctg ctgctggagg tggatgggga ggtggaatgg gtggaggatt 1740 cggagcaggt ctcggtggag gattcggagg aggatttggt ggtggaccat cagcagcagc 1800 tgctgcergct gctgcagccg ccgctggatt tggtggaggt ggacgaagag gtagaggtag 1860 aggacgtgga ggcsatggcg acggtaacgg agctagtgct gtagctgcag ccgccgccgc 1920 tgctgctgct gctggaggat ctgctgctga tgttgccgct gccgctgctg cagccgcagc 1980 tatgtacggt gacggtgctg atggacctga tttcgataat ggattcggtg gtggaaacgg 2040 aaatggaggt ggcggatctg gtggtggcgg atccggcgga ggtggatccg gtggcgqatc 2100 tggaggtggc ggtggatctg gtggatcagg cggtggcggc ggatctggtg gttcaggcgg 2160 tggcggatca ggcggcggtg gaaacaatgg atggggaaat aacggcaaca ataaatatga 2220 cgargatgac tgtgatgaat atggtaaccc tatta gaagg gggtaaatta tttgacatta 2280 tccgccattt gactcatttt tcttagttct ctatgtttta tacttcacct tagatcgttt 2340 tagtttgatt gaataaatta tgttttcgat ataaattttt tttaaactaa attaaacttt 2400 attagttgac ctgtaaactt tt'catggag ttataatcta aggaacaaaa aacatacata 2460 atatgtccag tattgtggta aagcacctgt accgcaaaca caatcacctc tatacatgta 2520 gtaatgctga tacaaaatca tacactctca caaaatcttc ectacacact cgcacacagt 2580 cctcttacat acacagcact ataatatcct gaacatgaag tttgtgttga taaaaagttc 2640 •• agaaaaatct cccctacatc acctgacctt tcactgaaaa tttacgacaa gtattgaaaa 2700 tagcagaaag aaaacgggaa attgagaagt tttctataaa aaacaaccgg aacaatgact 2760 ggaatgacaa ggatgaaaat aatgataact tacattaatt aaggccccaa taatctctct 2820 atcttcaaac ttttttttca aatgttctct ctaactcact tgcatccatg tggaaattca 2880 taaattacca catactatac caagtatcaa ggtttcacaa cttcatggca cctctcatgc 2940 atgctg gac ggtatttgtc taacaatgcc tcataaatac ataaaectaa ctaacaaaat 3000 aggtcagtct gtaacaaatt attaatgcac ttttctaaaa cattattgca 3060 acc caaagcatac gatatt ggcagacaaa atgttgttat tggatacctt tccactctat ctagacacct 3120 agtcatcata gctccccaca aataaatccc ccctatccca gaatgcccca aatgtcaatg 3180 accc ccccc cataatttta aaacctagaa taaattaaaa catctac? ^ atgat gt TGCTs 324C catctttctt atcatcctct tcttcctcct cctcctcctt cttcttcttc ctcctcctca 3300 ggtcc tggc tgcctgctcc ttccttgcca to 3331 < 210 > 32 < 211 > 5224 < 212 > DNA < 213 > Unknown < 220 > < 223 > Description of the Unknown Body: Unknown < 4 Q? > 32 ggaccccctg ctcgacgccg gcggcccggt acacctccat cgtgcggacg ttgttcccgc 60 gcccgcgagg g-tggacggag gtgccggcgt gacgctccac cagcatgtgc cgcaccccga 120 gccggcccag gaacacggac gtcgacaggc ccacgagcga tccgccgacg acgaggaccg 180 gaaccctgtg gaccgtgtcc ccggcccgat cggctcttgc gttcatcttt ctcctccagc 240 QCG gatgtc cgcccactcg gccggtttcg gccggggtca tgcatgcccc gcgaggctgg 300 agcgcggtgc gccggggacc acacttcacc cgcttaaccc gctgcgttcg cgcaggggca 360 cggcacgccc gacgatcgtg ctcacgggcc gacgcaccgt catgtgacgc gtcggccgcc 420 ttaccgttcc tccaggaaga ggtgcgcctc aatgacggtc tctgccgctg tgtccacggt 480 cccggaccgt gtccccctca ccgtgttcga cggttcccgg gtgcgggtcg tgccgatgct 540 ggacatccgc gacgggacgc aagcggaggt cctggacgcc tacqagcgga tgtccgaccg 600 ggccgccgsc gtgccggggc acatcagcga ccagctgtgc cagtcgctgg agaaccccac 660 ccagtggctc atcaccagcg agtgggagag cgcaccggag ttcctcgcct gggccaacag 720 cgaggaacac ctggagatgg tccgtcccct ggagccctac gtccgcggca cccactcgat 780 gcgcractcg gtgctgcgcg agacggccga ggagcgggcc ggggcgggtg cggcggcccg 840 gggcgcgctg cagccccggc cgcgcatcgg cgacaacgtg gtccggcacg ccgtcaccta 900 caccgtcaag cccgacagcg tcaccgaggt cgtgaagatc ctctccgcct acacctcgcc 960 gtggacgaca egaggtgcgc ccacgcggct cgtgcgcacc tccctcttcc tgtacggcaa 1020 ccgggtcgtc cgggcgatcg aggtgcgqgg cgacctgcag gccgcc-gc gccacgtggc 1080 ccggcagccg gaggtgcgcg ccgtcgagga agccctcacc ccgcar = ccg aacaggaccq 11 * 0 ggacctcacc gacccgcggt ccgcccggct gttcttcacc cgggccgcgc tgccggccgt 1200 ccaccacgtg gtgtccgggc gcgggacggg cggcgacacg cagcggtgcg cgctgtacta 1260 cccggcccac cccggcgccg gaccggcgct cgcccggctg Ctggcccgg c agggcgaggc 1320 gacccgggca caccgtgggc gtccggtcgt cgcctgcacc gtcttccacc gcgacgacct 1380 ctcgtcgaca cgtcgtacgg cggcgggcgc accggagcgc gcgeccgggg ccgtcctggc 1440 cctgcacgag ccggvaeg'cc tcgccqsgqe -cgggcggctg ctggacgccg ccgcgctcgg 1500 cgccgacggc cccccggacg accgggcgct gccgacgttc ctcgcgcacg cccggatgcg 1560 • • gcctctgaca gaccgtcagt cgccggcctc ctgacccccc gctcgcccga cctcagggag 1620 tgaccyacat gacagaacag caggcacgca tcgtcgcctt cgacgacgtc ccgcccaacc 1680 ggcggq_gcgg ~ cggcgacgtc cgggccctgc tcacgcccac gaccgcgggg gcgaccagcg 1740 gctecatggg cgtggccgtc gtacggcccg gagaacgcat ctccgagcac taccacccgt 1800 actccgagga gttcgtgtac gtcaccgccg gcgccttcga ggtggacctg gacgacgtgc 1860 cgcatcccct gcgcaccggg cagggcctgc tcatccccaa ggacgtgcgc caccgcttcc 1920 gcaac CCGG cgacgtcgag gcgcgcctcg tcttccacct gggtc gctg gccccccggc 19S0 cgga ^ ctcgg gcacgtcgac accgaggaga ccgacgagac cgcgccggcc ggggtggtgt 2040 catqagccgc cgggtcgtcg tcaccggcat aggcgtcgtc gccccgggcg gcatcggcgc 2100 ggcccggttc tgggacctgc tggccggcgg gcgtacggcg acgcgccgga tccccctgtt 2160 cgacccggcg cgcctgcgct cgcaga cgs cgccgagtgc gactccgacc cgtccgcgca 2220 cggcctggac gacgagacgg tccggcggtg cgaccggtac gtgcagttcg cgctggtcgc 2280 caccgccgag gcggtccgcg acgcgggcct ggacaccacg cgcgaggacc cctggcgcat 23 0 gggggccgtc ctcggcacgg cggtcggcgg caccacccgc ctggsgcacg actacgtcct 2400 g- tca CGAG ggcggcccgc qctqgqacqt qqaccaccqq cgggccgagc cqcacctqca 2460 gcccccagca ccgcgccttc cgctcgcctc caccgtcgcc gagaccttcg g? gcgcaggg 2520 cccggtgcag accgtctcca ccggccgcac gtccgggctg gacgoggtgg ggtacgccta 2580 ccacgccatc gccgagggcc gtgccgacgt gtgcctggcg ggcgccccgg actcgccgac 2640 atcgccgatc accatggsgt gcttcgacgc catcaaggcg acctccccca gcaacgacga 2700 cccggagcac gcctcccgcc ccttcgacgc ccgccgcaac gggttcgtga tgggcgagag 2760 cggcgcggtg ctcgtgctgg aggagctgga gcacgcccgg gcccgcggcg cggacgccta 2820 ctgcgagctc gccggctacg ccaccttcgg caacgcccac cacatgaccg ggctcacccg 2880 ggagggcctg gagatggcgc gggccatcga caccgcgctg gacatggccc gcctggacgg 2940 gactacgtca cacggacatc acgcgcacgg ctccggcacc cagcagaacg accggcacga 3000 gaccgcggcg gtcaagcggt cgctgggcga gcacgcgtac cggaccccga tgagcrcga t 3060 caagtcgatg gtgggccact cgctcggcgc gatcggctcg atcgaggtcg tcgcctgcgt 3120 cctcgccctg gcgcaccagg tggcgccgcc cacggccaac tacgagacac cggaccccga 3180 • • gtgcgacctg gactacgtgc cgcgcgaggc acgcgagcgg gagctgcgca gcgtgctgtc 3240 ggcgggcagc ggcttcggcg gcttccagtc cgcggtcgtg ctgaccggac cggagaggag 3300 gctgagatga gcgcaccccg gcgagccgtc gtcaccggac tcggagtggt ggcaccccac 3360 ggcatcggtg ccgagacgtt ct gaagacg gccgtggacg gcaccagcag cctggcccgg 3420 atcgaccggg agggctgcqg ccacctgccc ctgaagatcg ccggccaggt ccccgacttc 3480 gacccggccg ccotgatcga ggacacctac ctcgtccaga ccgaccgctt cacccacttc 3540 gcgatggcgg ccacccagct cgccctcgac gacgcccggc cctcccgcgc cgacatcgac 3600 tcgccgtact cggtgggcgt ggtgacggcc gcgggctccg gcggcggcga gttcggccag 3660 cgcgagctgc agaaact? cg gggccagggc tcgaagtacg tcggccccta ccagt cgatc 3720 gcccggtt ct acgcggcgag caccsgccag atctccatcc gcggcggctt caagggcccc 3780 tgcggcgtgg tggccgccga cgaggccggc ggcctggacg ccctcgcgca cgccgcgctg 3840 gcggtacggc gcggcaccgc caccgtcgtc gccggcgcga ccgaggcccc gctggccccg 3900 tactcgatgg tctgccagct gggttacccg gagctcagcc gcagcgccga cccgggccgg 3960 gcctaccgtc cct ccacctc cgccgcctgc gggttcgtgc ccgccgag gg cggggcgatg 4020 ttcgccctgg aggaggaggg cgcggcacgc gagcgcggcg ccgacgcgcg ggcgacggtg 4080 gccggccacg cggccacgtt caccggcgcc tcccgctggg aggagtccag ggccggcctg 4140 qcgcacgcga Zcqqcacqqc gctggcgcgg gccggctgcc gtccgcaoga cgtggacgtc 4500 gc rtcgccg cgccctcgg cgigccggag gccgaccggg ccgaggcccc ggccctggcc 426Q Qacgcgctcg gcccgcacgc gcggcgggtc cccgtcaccg ccccgaaggc gggcatcggc 432C cgggcgttct gcgcggccgc ggtgctcgac gtggcgaccg cgctgcccgc catggagcac 4380 qagctgatcc cgcccacccc ccatgtgctc gacgtctgcc acgacccgga cctggtggtc 4440 ggccgggcgc gtcccgcccg gccgcgcacc gcgctggtgc tcagccgcgg actcatgggc 4500 aacaactcgg cgctcgtcct gcgcaggggc gccgcgccgt tccccgasta agtaccccga 4560 aeaggtgtct cacgtcccct tcgggcgcgg gcacccgagt caaggagctc aaccacatga 4620 ccgacatgac cgaacgcgtg ggcacccagg tgaccttcga ggaactgtcc gccctgatga 4680 agcgcaccgc gggcgtgcac gtggaaccgc ctgacctgcg ggcgcgggcc gaggagggct 4740 tcgacggctt cggcctggac tccctgggcc tgctgggcat cgtggccgag ctggagaaga 4800 agcacggcgt gggactgcag gagcaggtgg agcgctgcaa gacgcccgcg g agttcctcg 4860 cgcaggtgaa cgccaccctc aggacggcgg tgtgacatgg ccgggcacac cgagaacgag 4920 stcgtcatcg ccgcgccgct ggacctggtc tgggacatga ccaacgacgt cgagaactgg 4980 ccgcggctgc tcagcgagta cgcctccgcc gagatcctgg agcgcgaggg cgaccgcgtc 5040 tcaccatgca cgcttccggc cccggacgac gagggccggg tgtggagctg ggtctccgaa 5100 cgcgtcgccg accgcgcctc cctgacggtc cgcgcccacc gcgtggagac cggccccttc 5160 cagtccatgg acatccagtg ggtgtacgag cagacgcccg agggcgtgct gatgcgctgg 5220 TCCA 5224 < 210 > 33 < 211 > 30601 < 212 > DNA < 213 > Unknown < 220 > < 223 > Description of the Unknown Body: Unknown < 400 > 33 gatcttagac cttattcact tgatacgtgt aatagttatt acgacagtat gtctttggcc 60 gattcctccg cgtcttcttt cgacgacgtg gaggtggagg caaaegcgaa gtagttgtgg 120 aagaata = ga attatgatta tcatgattat tattcaaatt aactctactg ttacgtaccg 1BD cgctccacgc agacgtttgc caggagacga cgggtggaag gatagga = c gaagaagcgg 240 aagcggaaga cgtcgtattt gaattcgaag atgataatga tgtcattcét gctgatgacg 30C • • fttrgttgtg ataatgagat cggcatggag gcatttcaca atctctttgt tcgcgaggct 3 0 taatctctga gcactcgata tacgaccgga tcgtcctgtt tcacaccaga aagcacgcct 420 rtttgcggcg ttgaactccc ccgccacacg atacagaaca ctggaattat tattagaagc 480 ttcaatgatg ttctaagaac ttacgtgagt ccatggagat atctgccaag aattatttgt 540 gagtggtgga catagttctt cattgcattt atcaaacatc tttggttctc tggtttcatc 600 gcaagaagac gaagtgcaag atacactgcg acgacgccat cccccacc "c aagaagcaga 660 • • gcactgaaca atcgtacatt agtaaattct aaatctgaaa attatatatc ccactrttga 720 ccaatctcca ataatccagg atccaatatg ttcttctccc tttggacagg gttcaagtcg 7BO gcaatttctt gcacttgttg gtctcttttg cacatcacaa tcaacatctt tcaaaatcgt 840 ccgaccaccg tcttccgcac tgacgcatgt aacatttcta ctttgttgaa catgagttcc 900 acaagtagct ggacactctc cccattccgc cattttccag tatgaacaat cacgaaggcg 960 ßcaatttctt gttgatactt ccttatccaa atgattgcaa tactcatcag gaagatcacg 1020 aacatgatct cggcacccga gaagacgacg ttgagtacca ttaccacáag ttgct AACA 1080 ggctgtccat ggcccggttg cccatcg? at tggtggtacg tcggctrgaa gtttttgaag 1140 tactctg gc ccatcacaag tatctttttc acaagtcttt tttaggcgtg gacgagtatt 1200 ctgaaatgat attttcgttc gcaaactgaa aagattaaaa acgtactoga tcacaaaaat 1260 attcatc ^ ac aatagttcct tcegatccac gagtacacga aacacttcta gtctgaattc 1320 ctgatccaca agtgactgag caaggggacc aatgacttgg tttccaacat gtacatggca 1380 agtttgacta gaagatggca gtttctggca ttttggtatc gaagcatcaa tccacaaaaa 14 D cagattgttc gcggt tatg cattcggttg tacgttcccg atgaccgstt ccac Aagata 15.00 cagaacactg aaacstattt atggtattga caacagcaat tctqga? tat ttgaataaac 1560 ttacagcact ccaatcagta tttctccaaa atgggcaagt gcctaaatta catgtctgat 162Q gagaagc ^ gg ccgatcagat gcagtaccac aaagtgacat atcgacttca gttscatttc 1680 cagaaacaca tgaaactctt cttgacgacc atccatcctc acaagaaaca ctacactgag 1740 accattctcc aagtttatat tttggacatg attctctatg acatggtctt gcaactatct 1800 aaggcaacga ttcccatttt tgttccggta gtactgatct atgacgatcg gcacaactag 1860 ctgtacacca cgtctcgata tctccacact tagctgagca gtcagaccag actccgaact 1920 gccaccaagt acaagcatgt tcattacaat gttcttgtgt ctgtgctgga ccacatctgg 1980 atgtatgcgt ttcccgatcg gctgcatcca aacattgagc atgacgcatt ttgactccac 2040 catcacaact tcgagagcac tctgaccaat gcccataaac ccatcttgga catggaattc 2100 tgttacattc ccgttctgtc gcctctttct gttctctgcc gcacaatgac tcatcaactc 2160 gacgattcga atcatcaacg caatatgact tccgatgcat ttttccattc gatccgcaag 2220 tttcagaaca tgaagtccat tctccatagt tccattttct tccagagcag tcaatgtaac 2280 • • AACTG ^ caat atcggatggt tttgaattac gatcacatag atgttcggat gctggagttt 2340 gacgatcacc ctccattttt acgcaagaaa ctcgttgacg tttctgtcca gatccacatt 2400 actagacaca tggcactaca tccatctgta tcttcagtga aatataaaaa tttattatag 2460 aaatctaatg aaaatatgta gtttaccttg tagaacaatc tatattgcac attcgtgttg 2520 cttgttttgg tttgagaaca ttttgacaat ttctatcatg tgagtcgaca actttgacga 2530 tgcccagaca cattaatttt tgcgattgct gtccacgaca ggctctatca cattctgtcc 2640 aagtacccgt aactctccac aaatacaatg cactggatat tggccgaatt acagcatttg 2700 gaacagccgc agtcatgtac tcatacgaga tgtcgggtgg atgactacca acagaaagaa 2760 catqaacata aatgtcactt ctaatcggac cagtcccatt tatccgttca ataattgcat 2820 atattcgaga cagaaccaga acagtgcctt ggaatgcaat gccagtgata ttgttggcga 2880 cttggaaatg accgttaagt aggaattcac cattggcggc acggagagct gaaggttaaa 2940 ataaagattt Ccacgggtat tgataacaca agggtgagtg atgaaaaaag taaatgttcc 3000 tgtatagaaa aaaaacactt ctcacaaaga taattgtcat cttctttcat attattatat 3060 cccccctgcc ggatatcaat atttgcagaa ccagctggaa tcttcattac ttcgttataa 3120 ccaaaggttc cttgctcatt aaatgttcct ttgacaacct tacaggaaga atcatcccca 3180 ccgcaaacac cacatttgtc tcttcggaga gttgatgatc gttgaatgaa acagcctgaa 3240 aatccactta ttttcaattt tcttttgaaa tcagatcaat gttacctgct ggcacacaag 3300 ctccagctac acaaatatcg tctccatttc tatcacatgg tgttcc = tca acaacttcat 3360 ctcgaagcag atagaacgct gcagatccac tgagccgaca atacaccrtg caacgttcat 3420 Etggtgcaac attcgcatat tttggaaccc agtgagtatt cgttgaagcg acaccttgga 3480 ttccaatatc tttattgttg aattcagaac attgaacttc acggtatggt tgagtatccc 3540 atgggcattc ttgtgtatta catgaccgat aacgttctcg ttgaccaaca cagcactttc 3600 caccatttcg aggtctaaag taatatggga aaatgtcatt ttaatattga taggaaagct 3660 tagccagtgt ggcctaaaag ctggaagttt ttttaaagat gcgttttcta tcaatttaag 3720 ataaccggct acttcaggtg attctataaa ttttataaag cttggaagct aggtaaatct 3780 aaaagcctt aaactatctc gaagcggccc gaaagcccag aaaagcegag acggacaaac 3340 • • atttaagagt gatcagaagc actccatacc ttgatgttac atttgacttt agtgtttcca 3900 cctcgttttc acttctgaac tcgccgattg aaaatatttt gattgaatat attatttgct 3960 ttcagactat ttgatatcat ttcgtttggc agtttaactc actttgggct gtcacaatcc 4020 cttaatcctt tttgaacacc accaccacaa gtacgactgc attctcccca tgatcgccag 4080 tcaccccatt gtccgtcaat tttggtaagg gattcggggg ctagacgaac acaggctcca 4140 tgatgacaga actaaatatc caagttttta tgagtttctt ttgtgattaa tttctgagat 4200 actcaccatg cttcttgatt cgtcacaagg agtcccgtcg gcccatggca tatgctgagt 4260 tcgacagccc atctggcttc cgtagaatgt tgcacaccaa agacggcggc atgtcggctg 4320 atgtttcatc taaaatatca tatttaggca ttaaagaata aacta = ccat ataagggcac 4330 aactcagaag ctggtccaaa tacaaacttg cactgttgat gagcaccgta tttctttcct 4440 ggttcatcac gtacaaagac atcctcgtag taacgacgtt cgaccggctg atcgaataga 4500 cattgagttt gacctcgatt atttctgaca aattgacaat taaatagaat caaaatttta 4560 atagctatct tactcgagga atcgttcgag cattccagct gaacacggcg accaactcca 4620 tggatgagtg ttatattcca acgttggtgc cattatgtgg aagttgttct gaaactgcgt 4680 tctatcaaat ttagtgcttt aaccttatta ggaacttgca aggtagagca aecggcatgt 4740 ttttcgttcg tcatcatgag gaatcgaaaa cacatgaccc aattcatgag caattgtgaa 4800 cgcagcactc aatccattgt cttctatgat cgcacaactt ttccgcatac caeacattgt 48 0 tccaagtcca gcaagtccaa gtgtaccgca ttttccttgt gaccgacaaa tatccttacg 4920 cgtcaaaagg attgcaacgt catgatgttg gacactcgaa tcatctggat cattgtaata 4980 ctgctgccat ctacagaaat cttgaagtgt ttgttgagcg ttctgagtga ttcgtggtcc 5040 • • agcgttttcs gttttcaaaa cgatcaactt gacaacaacg acattgatag atgcacgaag 5100 ggattggtga cgatagatgg aggcaactgt ggagaagaga gtgagaacgt agtcttcaag 5160 agatcttccg tgatattcgt acatttttgt atccgccacc acaaggactt caacatagtg 5220 atcccaagag ttggcagctc ttcgggatct tgctttgcgt tctataatta aatccttttg 5280 tttoataaaa ttatttaaac atttttttac tgtatccttc ctattaatct tgcaccccag 5340 agctccactt tgacctatct ttgttgtcat tgactctacc aaaaactgtt caactatgaa 5400 aatggggatg caagactaat aaaaggtatt ggtaactggt tccagtagag ctttccttac 5460 • • tatctgtttc attgattcaa ttttcagatg tttatataac catcttaacc gtccaaatet 5520 cataacatag aacagcctgg cagcccgtga aaaggtgctg aaatcccagt aatttcaatg 5580 gcattcgacc acacacaagt gatccattat cctttgctct tttacttcgt taactaccat 5640 tagctatagg ggacccacga gcaaaattct atagtttctg tgtgtgttag ggtgttttaa 5700 t ggctatta cacaacaccc gatgggatca gcagaatctg agatcttttg ggaac-GGAA 5760 aaaaatattg tgataacttc tcttttttct acatttttta cagaactagc aggtaaactt 5820 atctcgaaaa tcagattgaa atgcatccgc ctactcaaaa agtcgttttt aaaatgattg 5880 tttctttgtg tttgtcctct ttt cccgga cgtacgcaac acaaaaccgc ttgcgcgagg 5940 atgtacacaa aacqtacgtt ctgcgcaatc ttttccctgc agctctctct ctctcacttt 6000 ttctactcca taaatcagtt ctctgtctgt ctcccaccac ctaaatcatc atcagcatca 6060 tcacagtccc cccaccaagt tcttgtgtct tctctgacct ttacacgtcg act ggcaaa 6120 agctctcaag cagacactcg agcgccagtt gaaaaaaata gtgtgtccaa atgagcagtt 6180 accgtttgtt tcgaatttga cctgttctga cataaaccca ctaggcggca aaaaaacgaa 6240 ggataatcta aaagagatct aagaatctag acaaatttca gaagttctta ccaataacat 6300 cttcccactg atcttgccac gtggcaaccg tcgtctccgt ctcgttgaca ctggtcgagt 6360 taagacggtc aaacgatttg aagtgcattg gatcgaactt tcggacgaga tgttgcccat 6420 ggcgacttgc tccgtcgtgc tctagatgtt taaagcgtca gagaaagcga tCacaaagtt 6480 tctacccgct ccgtttccac taataattgg ctcaaccgta tggatcccgc tgggtagtgc 6540 aagcattccg tactgaaaaa ggcttttatt caccaaaatt cgaacccata caaaccaatc 6600 gtcgcataaa cgtcttccga ttgacgatgc tgtgctgatg tacaccccta acgtgtgcac 6660 atcgggatct ggtagataca gttcgagaca ttccacctct aacctcctcc tccgagtcca 6720 aatataagac catcggcgcg aaatttgaat tggaaaagtg gggaacactt ctggaattga 6780 gactgttata aaattaatac ataaaattga aatctcatac ttgttatgtg agtccggtat 6840 ttgattccat ctgtgcaaat gaacgatgta gacggcatca tctgatcgta atcgtaagtg 6900 acaagcatgt ccacagtctc tggcaactcc ttggagtcga cgtcgccgat ctgttgacgt 6960 gacatcacgc tceccacgac gtccataaga atctcttcgg acgatgtgat ggctgtcgat 7020 • • gacgtgtata ccggcgtctt gacgccatcg actgtgatgc actggcacac ctgaaactta 7080 tcacttcaaa gaacattatt acttttcgga ttgttacctg agtacctggc cctggagaac 7140 agcacatctg atgagaattc tgagatcgtg ccactccctg ctgaaaggaa catttggtta 7200 aaaacaaaag ctgataaatt aaaataatta gataaaaacg aacattgcaa cgcataaacg 7260 acgcagacga cgaggagtat gagagcggcg acgacgggct gcagcagatg gaatgagccg 7320 ccgatggagc gcataccaac agctccctga tgatgattat gattgtgtgg agagcagcaa 7380 gatggaaaga agaaaaaaga agcagaagcc ccgataaagt tcgtccgtct cttctgaaac 7440 ct ccaaaaa ctacctgctc gaggtcaagg gaagtcgtct gattgsactg ctactgcttc 7500 tgatcttttg ataatctccc gagtttgtgt tttcgtttag tcgaattaaa attgtagatt 7560 gtggaatgag cacttgcaat agggaaeaga gcatcacaga ctgaaaaatt aaaaatcatc 7620 gcaattttta tagaatgcaa aatttgtttt aaaatcactt attctgacgc catcttcttt 7680 tccgatttgc gcagaataaa taaaaacttg actgtaatat tgggaaaatt tcgaaaaaaa 7740 acaccgttaa gtctgagccc acctttcgcc tttttttgtt gacgaaaaaa accaaacaag 7800 ctttaaattc ataaaattcc caatctraaa aacatctaaa gtcaattcct cccaataatg 7860 cattcgtata tgaacaaaag tctgctgacc ataagtcgtt atattactac aagcaategg 7920 acctcataaa tcatcaacaa aatcagtttt gaacgggagc aacctatata aaccctgtgc 798th gctcttttgc tct ttttctt atttcttagt cgtcttctag ttccgccacc actttc ctg 8040 ctcttgacga aatctgtaaa ttgttcgtca tttttgattt ataagattcg tttggctctc 8100 ggtaggagct ctcaagctgc taatagtcct atagtaaagt actaaaaaca caaagaagca 8160 • • gatgaaggtg tcataaaaca ctgataagaa tcatcatgat taggttggtg cagagaaaag 8220 aaaaggagat aagaagaaga ttagagaaga gaaacaagaa taaaaatgca aaaataaaaa 8280 aaatagtaat aacaatgaac gcagagtctt ccatgttgga gaaggaacag gacccatgtt 8340 gatgtgtatc tgaggggatc caatgtgtag tgatggtagt aaacacttga gagggaactt ccacccccga 8400 ctagatgatt ggaagcaatt gatgatagat gtagagccaa agaattggga 8460 atctagtcaa cctoctaatg gattcttctg ataagagaaa aagacaagga agaacatgaa aatga 8520 < _tggt gattgaaaaa taaaacggtt tatgaagtcg gggtgtacta aagatgcaag 8580 • • gtctcttgtg acgtattttt tcttccaggc acgttcgcgc tattcacgat tttatgcaaa 8640 agtgttttga caaggtaagg attttgaata taaaaattta aagttagaca aaagaaatta 8700 ttcgaaaaat tagacaccct catgggaaaa attatagggc gaggagaggc ggtgagaggc 8760 gccctaattt ctgctcggtc gggtagaatg tctaatctaa atcctacctc atgtttggct 8820 ccttcttaaa tcaaaagctt aaggtcatcc ctgaaacgtg cagttgacaa gttcaatggt 8880 aagaacaggg agcaagcatt tacaacaaaa aagtaaacaa aaattgcatt tgtcgcagtt 8940 caactcactc caaaatggaa ccactcgaga acgttttgaa agaagaggaa ggggagagga 9000 ¿atcatcaca caggcacatg gaactcctgg gacacaaaac aatacaaact gggtgccgtg 9060 aa cacacacaca ctcagta aaaatcaaaa aagacggaaa ttaggagcag atgtggtaaa 9120 gggtg TTCA atgctgatgg gagagagagg gagaaacttc aaaaaaagaa gttcagaCCt 9180 atgttggcta cttcaatcct aeatttatct aaacaattct aaaaatgctg gttttggaag 9240 gttatctggc aatggtgaag ttttataaac aaaacaagac aaacaattct tgagatctta 9300 aaaatcttag cgactacaac aatatttagg tattttttaa tggaaaaaag tattgattgt 9360 tgacttggga asttgaacag caattttttg tacttctaaa tcagttatat tttaacccct 9420 ttcgtagaca cagagcacat aaagggaaaa cgattggtcc aacatgtgaa gatgatgatg 9480 ttggatcgga tcaacasgtt gccaaaaaag aaacaaaaca ttcata cat gatgggaaac 9540 aagaggtgca gcaacasctc ttatcaatat tttgtttatg ttttgaccat cttccggca 9600 cccaaccagt aattcttttc cgtagagttg acctagaaaa tgttggaggc ggagtcttag 9660 gatcaagaga cgcagactat caaagtaaaa tgagtaaaag gaagtgatat aaacttagga 9720 aaaaggacga aacggaggaa tgataagaga ttgaagaett ggaagagtgt gctctttgcg 9780 ggagagcata ttcttttgag aaaaatggga cctaggggca actgacgcaa ttgaaacatg 9840 gtcgagcggt cggcgggaag acaaaaagtg aagaaggatg ggcaagaaga agcaagagaa 9900 ccgtggaaca atggcaccca tgatcatgat gattgagagt gaaaattgga aatctcgaac 9960 cggcgcgttt ttttttgcaa tggaaaacta acaaagttga ccaaaaaett attttacatg 10020 tgtetaagaa tataccggga ttgtaaaatt gagtgatcct ttctgtgaca taatttaaag 10O8O caatetattt tggttatttc taagcgcctt tttatactag catgetacat tgttaatttt 10140 attatctaaa ctgccgttct tcctatattt attattgcac cccctttgtt cattctgaca 10200 cgattaatca gactatacct taaaaatgtc acaaaagaat aaaaacaact aa aattaaga 10260 aatttatcaa aaatacaaga ttgccaaaaa ttcggccaat cggaaaaatg cttggttgcc 10320 aatttgtcaa aaatttagtc aattggaatt tgtcgatttt ccgaaatgat atgaaagttt 10380 gaatcatgea gctaatttcg cagtttaagt ttacattttc aagtttactg taatttttcc 10440 gaagagtttt aaaatatgaa acgaaattaa aaqataataa aaaagceatg caaacatage 10500 tatgaaatct gatcccgact aagtttgatg gacataggat taataatatt agtctaactt 10560 tet tagaac actaaataaa tacatteact ctcgaaactc tcccttttct gccatcaact 10620 accstactca cttttgactc aatgacccgc aactgtcaag atgagttagt ttcaagatte 10680 tctgaaacag caataateta acaagagaaa ctgaaaaaat agagtaaaac taataataat 10740 ttgacatgca accacataaa tgatagatga ttttccggtt ttcaacaaga aaaacaacaa 10800 ateetcatag tttccgagaa tttttggtaa gaaaaaataa attgatagtg atacggtatg 10860 actattacct ctaaagactt acctgattag aaacgtgtag taattgaaga agaaaagttg 10920 gttgaatcga aatttgagaa gttcacgatg tctgaaaaaa acatagstat tatggtaaga 10980 tcaaccatag aaaaaatgga aaaatacaag aaaatagaga ctagagattg cataggtttt 11040 gcggtggcga aaccgcacac atttttgtct gtgttatctc taat tttacg ctctcggtgt 11100 ctgtccagaa tctctattta gaatgaagaa tatgggggaa aagtgcgccg gaaaactgas 11160 agaccgagtg atgagagccg cagttttgca aaactttttc gggcaataat ccgccggcga 11220 gtactacgag aagcacacac acatacgaaa actgttgagt taaaacctaa aaaattgttt 11280 aattttcgaa cgacatattt ctaaagttta gagggtctgt gcgtgcattt ttgaattttc 11340 caaaeaactt tcagttttgc ggaagaaaat tacagcgatt ttttcgaata tttctgaaaa 11400 gcgtatcaaa caacactatt aatttttcga tttgccaaaa ttcagactaa gttttggtgg 11460 caaacattta ttttggtttg aaagaactca aaaaacattt ttagatgttc gaaaccgtac 11520 aattgtagga tacaaatagc tacagaacaa ttagaatata aaatagagtt gtcaaacatg 11580 tccaactaat acaaaaacac agaaactttg aaactcgaaa tttttatatc aaaatcgaaa 11640 aagcttgtaa aatttaaata tggatacagt acaaacaata taatcataga ccaaatagtt 11700 • • catttattta tatatcttgg caaatcaaat cgtatccctt acccactcat attcg3tgag 11760 tctacaatta aatcagttgt tttttcatcc tcccggacta ttagtttaac ttccacttga 11820 acaagggcaa agagtacatt aggaagagtt tatgatgaca ggaaaaaagc tatgtaaaat 11880 gacctctttg gattgaaaaa gcgaacgaat tgaggtttag gacccccgga aaatgaagaa 11940 ttcgtggcct cgagaatagc aaattggcgg aattaattat ccgtaagagc gtgaattgga 12000 aacaaccggg acgaatggat tactgaatca aaaatgaaag aaagaagaga cgaaaatacg 12060 tgtgaatcgg atgaaatgtg atgattttag aataacctaa acgcaacaaa acgacgtaaa 12120 gacgcggaag aacaggaatg atcaaggggt acatcctata ggggaaaaat gcactttttg 12180 tgctccaaat gtgagagata atcaggtagq aagagacgta gaacaggaac 'aggaaacggt 12240 aacgacagtg cgcaggtgct tgatttctgc gcttttgcat gtgttccgat ggaatttttg 12300 gaacttttca aggggtttcg gaaagggttc gagatttcgc atgtgagctt tggaagaatt 12360 tttcaggata ttggaagaac acatcgctca agcttgtttg ttagatttca getcttcaaag 12420 tatataccga ttattgaaac attttaatcg tttcttacta ttagtaaagt ttaatcacag 12480 ttt Saaaaa aaatcacaat tttttcaatt atttagac ca 12540 aactaactat ggcacagaaa ataacttgca accsgggtat ttcattctaa tttttttcat ttggaaccac tagtttttga 12600 aatagaaact cgttaggatt cttcacatat tatcataact atcagtacct tgctccacat 12660 cag = tctaag ttcagtctaa ttagaatcgc aaatttgacc atcacacttt aaaacaaatt 12720 tacccaggca cagggcatcc .ttctaacttt ttcgtccccg acaaaatgat gacaaaaatg December 80 tcaaggagaa acgtgaggaa aaaggaaaag aacaggaagc gaaaagtagg agaagctctt 12840 gatttctgtg ctcattcctt gttcggatga gctcactgtt tgcaacattg gcgttggtgc 12900 gcgggaatcg ccattgccga actttttcaa gagagagaaa gagacagaga gagaaggaaa 12960 acgttccgat ttttaaaatg gaaaaaaatg aaagaggaag atgatgaaaa aatgaactct 13020 gcgtgacatt tgttaatatg gaaaaagcat gattacttca aaattgtaca ctaatcccca 13080 cagcacacat tttgaagact ttttcacaaa aacaatggtt taagcaagct ttaaaaaatt 13140 getagtatcc ttaatgctta atcatatcca agtttagttt taagttttga tttcaaaaat 13200 aaaaatcata ttctacatca cttagtgatt atatgcaaaa caatttttaa attcaaggac 13260 • • atattCCCga Cttttggaag gatgataact cttttgtgat tccgaaaaag at taaagtag 13320 gtttaaaacc tctgaccttc tacagaaaaa acattacctc tatgaattct ttttcatctc 13380 gttcagaact tgtctcgggt caagccatga agacatgaga tagggtgtaa aacgttccga 13440 atgactatta agagaggttt ttgtagttga agagaaaaat gatatctcaa tggatttcat 13500 acagatggtc ggatttcatt cataaaatat cataagaaaa tgactgtcta ggtacgtcta 13560 ggtcaactgg ttttaggttt cttggaattg t tcaaacat ttttaggaaa tattttcttg 13620 ctaaattgaa caaatatcta gtttgttatt gtttttgaca tattgtagat tttagagaag 13680 aatcactcag agcaaaaatg ttgggaaaac gtgagaaaaa tccaagasac asaagaatgg 13740 cettactntt agtagatcaa aaaaccagac caattattca tattcctact attcaatata 13800 tattcaaaaa tgagcaaacc aagaaattgc acctaattta tcatcccaca tatattccga 13860 cgaaacattc gctctacctt ctttttttct gtctaggaat tataaagggc cataactata 13920 aggtttcgga atcccagtca aaattgttcg actaaccatt atgaaagcta aaaaccaatc 13980 cacaatagga agtcaaaaca atataaaatt cgtagaagaa aagctttctt tccggccgaa 14040 aattctggaa agcaaaatca ctgcgacttt tttagtgca to ttatccattc aacgcaagtt 14100 gtctttcaaa atttaaattc cagaagagtt ataacaaaac agacaggcgc acaagtaaaa 14160 gaaaaataca agttttatcg taaaaactga cacgaatcta gatacarctg ccaaaaaagg 14220 ccctctcgaa acccagaCgc cgtacgaagt aagcagcagc ttttcagtaa caactsaaca 14280 acatatggca agtgttttgg cgcaaattgt aaagattttc cgtgtgggta actagaattt 14340 gaaactgtaa gtatgacgac ttaaccacac aaaatcaaat ttcaaaagat cttaaaatgt 14400 • • tcgaactttc aaaactttta agctctctcg catctaccgt agtcttctaa taacaacagt 14460 cgtaagagaa agctcaaaat ttttcaaact ttttctgaat gttgtataca gacagaatca 14520 aaaaaaaccc ccaaaatgcg agccccatga acctgacaac cagacaagtc gaaattgtaa 14580 aatcgtatag atcttggttc acgacatgaa gagcaccgcg ggggcacacg agagcaacta 14640 ctgcaagcgc tcctgaagag aagaaacatc ttttttccag gaccactggc cagtagtgct 14700 cccccagatc actttctttt ttcttgcttc atctgatttg tgtctgcgtc gtctgatctc 14760 tttag < »Acct atccttcttc ttcttctttt tgatacttcg acatcagaac aacatcgaca 14820 • • tgtatcatct tttctctttt ttttttgtta tctattcatt cattcacttt tcatttagtt 14880 tgattaatag gtgacatgaa ctcttgtcac ttttcaattt caacttctta aatcttaaac 14940 tcacagtgat tccagatatg agcaactcca atgaggtgtt gagtagaaac ctaaatataa 15000 gttttgataa cattttggat tgttggaaca aataaattga acttgaaata aacaaacaag 15060 gagacaacgt gcagaataat gtctaccagc tggtctcagt ggcataccgt accacgaacg 15120 tccgacagaa cgaataacat aaagatcaag aaaaactgtt caaacaatca tgggagcaga 151B0 gaacacagtt ttgttgaggg gaccaaatca ctaaatttta taattaatga acgaagaaag 15240 tgctcgaaaa gaacagaatt tagaagttga tgaacaatac tttcactttt agactaacaa 15300 caaatgacat ttatgcttta gcatctggr.a ccaatctaaa atctgaaatt tgtcaaaaca 15360 ctagtttcaa gctttcaaga atttgtcgat tcaatggacc aagtgtgtaa ttgatccaat 15420 aaaaaagagt ataaagtgag aaggaagaaa gtgtgaaaaa agaagaacgt gaaacgtgca 15480 gaagatacga aatgagtttg aagactgcac ttttcgagcc tcgatggtca gtcacttggt 15540 aaagctgtga cagttgcgaa aaatgataca ttgtgtcggc tctcgcagag aagaaagcca 15600 catggtcagg atgactccaa ctgggatatt cagttgtaaa gaacacaatt gatatttttg 15660 catccttctt aactagtttt tacaatatga gaaattgttc tgtgcgaaaa atatgacttc 15720 ccgaagtgta ttccttgttg tttccctgga aattccagta aatacctaat gtaaaaaatc 15780 tcagcagaat gtgtccttac attttgccgt aataataatg tactaaaacc gcattaacta 15840 aaaatttctt caaaatgttc ctacgtcttc tatgcacatt atttaggtca cagtttcatg 1S9Q0 cacctgccga gagcacaaaa cgcctctaaa atagttataa ctgcgcatga aatcaggtag 15960 aaaataacca aaaaaactac atacaaattg agtagggcga tggagaggcg ggcggttgga 16020 gaggcgggca acaagcgtcc tcatgacgcc ttgttcattt agaatgtgtt tgctttgaat 16080 tacatacaag tttctaaaat ttaacttaca aaagtcacaa aaatttaaaa caataataaa 16140 agttgtggca atgaaatgtt ttaaaaatct aaatattgag ttttaaataa atgatttttg 16200 aaaattcaca aagaaatgtt acaatctgtg aatgaagacg aacaatgaaa aagtgaggaa 16260 cggacgcgga tattacacat tcagtcacac aataaacgtt cggacactac cacacatttc 16320 tctcatcatp tttttccaaa gtctattcta aagttcaata ttttagtttg attattttgg 16380 acactattct taaaattaat gtataatagt ttagaaaata ttttgaaaca tgaaactttt 16440 aatagtgcca tcgttgataa aacatcctta tgttacgcag ttatccaacc acatttttct 16500 ccaaaaaaca catttttcca ctgaaatggt ccataaaacc tattcaaatg gatatgagaa 16560 tattactctt ttgacatgaa attttcaatg atgtaatgta aaacaaagaa aaatattgcg 16620 gga aaaattg aacggcgtat tgcaaaaatc ggtgtgcgga ggaggagaag gaaaaggaag 16680 gcggaccgaa agcaggagaa gaattcagaa gcttttaaaa gactttcaga taagaacggc 16740 caaacaatgg actgttgtat aaaaataaag cggaggcggt agagagtcaa agctttcaga 16800 aatgtattag aataggtttc actacctgtt gttgaactca aaaaggtgtg aaaaagtgaa 16860 aagtttatga agtttgtctg cgggaagtijt ccatcaaata actttcaaaa tttgacttat 16920 cagtgagaaa aacacgtcat tttggaacgt taaaatgggt aatgttcaca ggcaccgcaa 16980 atgtgaagtg aattacgtaa taaaatcagt tttattaagc ttattaaact aacccttccg 17040 gactatttgt ggaatgaaac aattgggggg gttttttttt ccaattttcg attttttttt 17100 gaatctataa ttaccggaac aaaaatatct ttaaattatt aagatttgag tgatgtttga 17160 ctgcaaaaca aattttgaac taagcacaaa ataatggagt ttttgttcta aaatatcaat 17220 aggtgttttt tcacagaact ttaaacaaca atttgaatga aatactcata aaacagtaga 17280 tccc = CAATA ttttgaaaac ttatctatat atatatatat tacqaaaaa acatacacaa 17340 gaaaaaaaca aaaacaaaaa cagttgataa aataatttgt tttttagata tcagttgcca 17400 atatggtgaa aaattgggca gaaatacggt agttcgccgc acCgtcagac taactttcaa 17460 gtgttcctag tggaatgaaa ctaacagaag ctatacggta tataatatta ggaacacaat 17520 taaaacgaac agcggaagaa aagatctagt ggtcacttcc gatttctcag ctgacttttg 17580 aatgggcacc tatcatcatc tcacttgttt atttgaacag tctcgacttt ttccaattgt 17640 tggcttctag ttcaagaaac gaaaaaaaga gcaataacgg aacagaaaat tcagaaagtg 17700 gaagagaaat atgagaaaat gatgatgata ataataataa gttagaagag ggttatcgat 17760 gaggaacgga aacgttatct ctgatc cca tctcattatt attatgagac acaaagatgt 17820 atctttgaaa aagttatggt gaaaagaaaa caggaaatta tacagaacac acacaatttc 17880 ggagatttca ttcgaagaac ctaacccaat ttgaactcac tcccacttcc tcctstctat 17940 atcacaggaa aaaacagtca tcttttcaaa caggtgtctg tttccgaata atgtatacgt 18000 atatcacaga atgacacaca aatgaggttg caaaatgacc tgcaaaaaaa cagaaaagaa 18060 tatagaaaga gagggtgaac aggagacaga gaatcaaaat ttgcatagat aaatatgcaa 18120 caatttttga tagaaaataa acaacaaaga aataatttag tggcatat ^ a tatagcgatg 18180 atttccagaa gaacttgcaa ttatcatata aaaataacaa tgtttctata ttttatgccc 18240 tat = agcctt gcagtatttc ttaaacttaa cattttcatct cttggtaatc ttt attttta 18300 tcaagaagtg tteaggaaat tttaggacat caaattttta tttattttct aaatctactt 18360 tcaccaaaac tttagaggtc tagtacacat ctacccaaaa agaagactct ggagctctca 18420 aaaaccacct agtgtatggt aaagtacatg agaagtgacg cgtctttggg cagctggcca 18480 tctttgtcga tatgcgggtg atggtgtttc tgtgagcagt aacaggaaat tctggacacc 18540 tgccagggtg tcaaaccaaa tttattccaa cccattcttg cccccaacta cttcaaaaaa 18600 attctcgtaa aattactcaa tttaatgaat cactcagcaa cCgtaacgtt ttttttttca 186C0 tcgaaagtta gagacaatga ctgaggatta acaaaaaaaa ggtatctaca aacgttattt 18720 gctgacattg aaaagtggta gaacatatca agtgaaagtg aaacgaaaag tgcaacattt 18780 gtagaaaaga gaaattgaga tcattgaagc agaaatacgg aagtgaattg aaagccgtgg 18840 cgccaaaacg acggtcaggc aaattaatga gccattgaga ggttgaaaca gagctcgcaa 18900 aacgtgaaaa acacaaagac attagtttgg agaagataaa aaacgtctgg agatggacga 18960 tttcttagtt agctgagaat agtttacatt gattttcggg atgttagaaa aaaacgcaga 19020 aatggaaaca tgtctagact tcagataaat ttgtagaatt tatatttgta gcaaaagcac 19080 actaacaaag gttacaaagc tattaggaaa aatacggaat gtatttttg to aaatttttga 19140 tttctctaaa ataataacac cattaatttg ctatatttgc tatatatgct atatagtatg 19200 tgagcacaaa ttcgcattac acttggaaaa agtttaaaaa aaaaggaaac ttgttttctg 19260 gagaaatcat taaaaacagt acaatttcag acagaaataa atctttcagt gaaagctttt 19320 ttttgagtaa gactaagtat gcactcacaa cttttctgag tgttccaaaa atgtttaaag 19380 aaaatactag taaaaatgag catttcgaaa agcaatatat catacaacta cacaaacatt 19440 tcaattaaag gaatcaattt tataatagtt ctaggcaatc ccacttttag attcaatttt 19500 • • ctagcacagg gagcattgga agatataaaa acataaagat aaaggtgata aaagatccat 19560 taaacacatc atatctatca aaccatcact Cccatcaaat scacagattt atcacaaatc 19620 agtgtgtgac aaatataccg taatattaag ttcaaatggt ggaaaagacg cagacaaagc 19680 atactaaata ttttgcataa attgaaagaa acgcagagaa tgtaagagaa aaatatacaa 19740 tatgtgtatt atcaaccatc aacagttttt gattaaaacc atggagaagc gatatacagg 19800 agcaaattag gagacgcaga ttgagaaaaa atgagaaaat aatgaaagta cggaagggtt 19860 aagacaggta attgtacaat gcatctctca aagaacctat tgtcaagcag tttaaacatt 19920 caacaacgtt catttatttt ttagctttca ttatgatatc tcattggttc tataattgga 19980 ttttttaaat tcagatttct cattcatgta caagtaaagt tgttaattgg ttattatgcc 20040 caaagtttaa ttatttgagc gcagaaaatt tgaatggaaa tttcagaaaa ctgattcatg 20100 aaaatcctga ctaacttcaa ataaatacca attcttttcc aagtatgatt ctcgagcctg 20160 tttacgtgcc tgcctacggt ctattttcta atttttttaa tgataaaacc ttagagtaga 20220 tcttccttaa tcttcaaaaa aaaatctcca aaaaaatcaa gttcaggaaa actaaagtac 20280 cccaataaaa tactcttatg caaaaacccc ccattcattt tgcagaaaaa gacaaacaag 20340 aattaaagat aaaaagtt? t gatagacagg aagctgattt attagatcaa tgaatcgact 20400 tttagctttt cttgaactct aatttgaaat agtattcgaa tgagaaaact gaaaatatac 20460 aaagatcaaa agttataatt gaaaatcaac aaattgatag tgtttgtata g attaaatt 20520 aaaatgtgcg gtacatgaga cagtagtagt agtagccata gtacgtattg gcggctccac 20580 tcggctactg ataatttcct tttttactga taatttgatg tcatttcgta attttatttg 20640 tgtttccaaa aattgtgggc gtggtttatg aattggtcaa gacatgaatt aaaggaattg 20700 aagaaaatga taaagtaaag cagaggagaa attattttcg tttgctttgg aaattgcaaa 20760 ttattaaaga ataaattaga taatagttac ggtttaaaat aaataggtga taaaaaaata 20820 tccaaaagtt caagtcctaa gaatcttgct attttgcaaa aaaaaagcat gagcttttgg 20880 cctaaaaatg gcggacagct gtcgggacac tatccaagaa ttcgtgataa acgggtgaag 20940 caccgtctct tatcatcatg ccatttttcg aattttaaac tcagactttg ataaagaaaa 21000 ttaaaaagag agagtgtgag aaataagagt acacatggaa aatgcaagat ttgaatttgt 21060 • • ttccaatccC taaaatgtat ttaaaagagt taccgttcca tttttgatta gctttataag 21120 tggaaaaatc gtttttggat tattttttga ggaatatttt tgaatgcgct ttcaattttc 21180 ctataaaaaa ctttgtgttc acttttttat cccgttttta tttttatttt tacaacttcc 21240 aaacttttat gaatgttcta ttgtaaaatc ataaaaaggt gcgaaacatc taaattgcct 21300 taaaagtgca ggattgcatt ttagcagaaa tgtattccta tggaatgttt tttgtgcaac 21360 agctcgaaaa gagatccaga acatccaaat ttcttccaag aaagttgatg ttccaaaaat 21420 ttagccca aaaaaagatt ^ t caactaaaaa aaaactctcg tttttttcat atttcacatt 21480 tctgaaggaa ttctggtcac caaactgaga acactaatcc gattaaacca accgaacatg 21540 tcccacttac tatttcttgt tgtcttcaaa aagtcttaga attgtgcaaa aaatagaatg 21600 tttcgaaata ttgcggtttt cgttaaaacc ttttttgagt agattgaggg tccattagaa 21660 ttcccaagag aacttgatg-to cctccatcat ggtcattgaa caaaattagt tgcttgatca 21720 gacaaaaatg gaaatgactg aatcggaaag agcaagaaaa tcgaaaaaaa aagtatttgg 21780 aaacttttta aaattctgga aaatttaaga agggcaacga taagaaacag gaaattaggg 21840 attttttagt gatggagaag tacgtgataa ggttaaggt g gaacactagt gcacacgttt 21900 tgaatacact acgtgttttt gaatatagca atttatggta cttaaaga = c gtttttaata 21960 caaactgaaa taaaaatacg gaaatgtaat • tccttttcct gaaagaaccc gcccgaaacc 22020 gaattttcac atcaaacggt agtgattctc tttatgcstt gggtgatatg tatttacgct 22080 gtctcaaagt tttcgactat aatttaagta atatgttcgc caaaaatcac catggcgctg 22140 cgtcctatgt agccttttct acacttgaaa aatgataatt tttatttgaa aatggtattt 22200 aaattcaagc agaaagttat ttagtcttgt gtgccaagca ataaacacat agtctattag 22260 gcaacaaaaa gtcagctact gcttgattta aaaacttaga ctaccggtgt gcctgtgcaa 22320 gtcacccccg tagtacggat acagagtgaa aactagtgat tgtactttag atcggctgat 22380 cagagaaata agtgaattta attataaaac ttaaaatttt tagcagctca gtcttcaggc 22440 tattgttaca tgcacagcca cttggagtta caaattctgc aaaceatcta ggattgaatg 22500 gaaagtcaca caaaaactct ccaacaaaaa tcaagaaatt tgccaactca acacattaga 22560 ttgattccca ttgaattgca agagaaatag tagtaaaagt gacccctatc cattcctccg 22620 • • ttacatacaa atatacacac aaaaaagagt gtagacctct tcctcctaac ccaaccaaca 22680 cacaacaata tcgttccctt ttatctctaa ttctctgcgt ctccataagc tttgagagct 22740 tcttgtgctt cttcggagca cggcggtaca gctccttgca gtttcctecc tctgctccct 22800 tatgtgtgtt taggtgttgt ttgaacaaat aagtttttgg ccatccacct ccttctcaaa 22860 acctttttct tatgcttctt cttgttttgt GCAC = ttttg gctcttgctt gtctgctcga 22920 gccatagaca aggcggcgac atttttgaaa aaattatatt agtactgtta tatagtactt 22980 tcacaacaac aatacaacga aatgaaaaca aacacaacga tgagatcaaa agacaaattg 23040 ttaggaggag ttggagtCCc tacaatcatg aaatgttcat taaaactgaa ctagttatca 23100 attgctcata aaattgtgat accatgaaga ccgaaaaact ctatgcaact gcatactgca 23160 catacttaca acctttattc tgacttgaat ttcagttttt ggtgtttgca gttattctat 23220 agaaaattca tttgtttaaa attaggaaat aagcaataaa ttttggcatg tatttcgata 23280 gtaaatgcca gaaggsacgt agaaaaaata cccggaaact agatttctca aactgaaaat 23340 tgaaaattta gattgtgaat tgcaaaagta agagaatcat tcattttcca cacaaacgaa 23400 gattgaacag gaaagtgcag aaatatcaga ttaccgtccc aacagaaacc ggaaacaaca 23460 cttttcaggt aaagaactat acagaaatcg taataaattt aaaacaaaag agagttatga 23520 cacattgcag aacggtctct gtggaaaata ggaggaggtg ctgcaaaaac tccttasaca 23580 tggtcatact tacaaaaaaa acagagttta actaaaaatt aaattaagtg agaaaacgaa 23640 gaaaacggag gtccttcgcg gattcatttt acttcttctt ttttccactt ttcgttgcaa 237C0 gctttggttt aaaagtttcg caaacaaata aacaatgaac attgtgttga gaagacaagc 23760 • caagtgaaag gaaaccattg agagcaaaaa caacaatcaa ttgaaataaa gagtaaagtt 23820 tattgaatat actgatatgt gaatactgga aaaataatta gtctctataa ttggtaccgc 23880 ctggaagatt catttctgat tcccttgtgt ctttgaccaa aactttattt ttttcagttc 23940 aaaataaata aaaattacaa ctcatcttca tcgattcagt ggtgttttaa actcctacgt 24000 ttttctttta caataaaggt aatgtaaacg ttccgagcgt gtagttttct ctgaaaattt 24060 tttaaaaata acaactttat ggtatttttc ttaaagtctt aaastgaaac cgaaacattt 24120 aactatttta ttgataggaa aactcggcaa acattttggg ggcttgccga aagctctgca 24180 • • acaactctca tt ± gaaagta ataaatatga aaataaatta tcgaagtttt tttttttgat 24240 attttatgaa tacggctctt ggtagttttt gacgagaaaa ttacatgttg cataaatttc 24300 aagagttata actcatggag accctaattt ctggtttcac tagaaaatca aaaaatcaag 24360 gaagactgta cgtttgagca ggaagagcac acgtcataaa aattagggga tcaacgatcc 24420 gaaacgggga attgaaatac gatatgcgat gagttttggt tcgaaccggc tttgtcccaa 24480 aaaacaacag aacgatggtc tcaggctcoc ttgactcatc tcggtgggaa caatttttat 24540 tccgtacgca ttgtttttac ttttgaggta cagaaacttt tttttgatcg tgggtgggtg 24600 gaatggtagc acccaatttc aaatagtgtt tgatttgaag agacaatgaa agaaacaagt 24660 gggagataat ggaaatgacg tgatgaaatg gaacggagga aaactggtat aaatatcgct 24720 actacaataa gactatcaaa gaaaagttca tactaatgga agattttaca ggactcttga 24780 ttatgatagt tgggatttac tggtttcaag ttcaaatgtc aaacatctgg aagaaaaacg 24840 catcaaaata tataagatta ttgaaggata aaactaaaat gcataatata aagtaaaaca 24900 tctcatgtag gtgttttaca gaaacgaaca aaatctttga acacctagat aacttcaaac 24960 ggaagttggg tgaagaaaag aataggggcc agaatagaa g gtcattctga caaagtgaac 25020 agacaaagac attcctaact cggaggtatt ccaaaaactg ttcca = tatt gaagaatgac 25080 actatttgat tttatatcat aacattatta atcacatggc tctcttccta ggaaattcat 25140 atcgcaaaat aaaaagtggc cttgatgagt cattcattca aaacatgcct aaaaacctcc 25200 ataattaatt ataaaaatgc tgatacttga ggacccgttt ttttatattt ataaacagtt 25260 ttccgttctc gttttcttta actttgagtt tttttctgaa aatactaaaa aaattaacaa 25320 agttcggcgt tttttgtcga taattccate tgattatttt cggttttttt acctaattat 25380 caaatatttt agccagagtg aaatttatta tcttattaat atgtttttca atttgttttg 25440 gtattattct gttgaaggaa catgttgcat tttaaatctg ttgttaatac agcggccaca 25500 tgtttagaac tttataacct cgtttaaaca taaattgtat gccatattta ttgcaagtac 25560 tacatgagtt tgaaacagta tcagatacta tattttaaac aaaaatacac attttccccg 25620 ttctgataca ctatgagaga ttggtttcca atttttttaa aaacttgaaa ttcctcaagt 25680 ctcccactga attacagatt tctgttctag atacctccaa agacacctag attcgacttc 25740 • • ggcatcttcc tcatttttat cttcagtttc atcttttgtc taattttccg tacatttctt 25800 tgcatcctta ccatctctcc ctctctcact cactcttctt tctcaattca gttcactaaa 25860 tgccacgcca aaatgttttc tcatcatcat caatgccacc ttctcagagc ccattcgaaa 25920 aattaccacg gcatcaaaat attcgatatc acgaaaaatg cttctcaatt ccacttcata 25980 cacttaacta ttttctatgc gttattattt tttatttctt tgttttcacc atattttatc 26040 tggtggaaaa acgaacgtta cctgaaaatg ttcaagttac atcagcaatt tatgattcaa 26100 actgtcatta attcaaacga atctttctat ttgactcttc aattcgtcga cgggaaatat 26160 cccctggact tggtccaaat gactcaaaaa catcaagaaa tgaaactcaa attgagctta 26220 aaccaccacc cggatttgct gataactcac aaatttcagt aagtttagga ttttttttca 26280 Ü »aaaaaacttg atatgaagtg ttgaaaaatt gataattggg ccgggcttac atcagagtat 26340 ctagttatct tgtatttcaa atattaatat tcaaacattg tagagattcg aaatgcgaca 26400 gtacttcagt aattaccacc cacattttga ctgtcaaaaa agttcccaaa aattgtcgaa 26460 aacttctatt aggatgtttt ctcattttgg cacgattgga gtgttttttt aacaaatccc 26520 ttttatgcat caaattaata tctaattttt aaatcaataa tttggattaa ttcaacttgt 26580 tttataagat tttctcgcta ttaaattagc aaaaaaaaac tatcttcaaa caattagcgt 26640 gctttaaaac tactaggcct ttgttggcaa catttcggca cgtcttttca caaaaccata 26700 aactatgctc agaatttggt aatgtttgaa aatgttttgg gcaagcatat agttactcca 26760 attctaaagt aagattagtc atctattttc cattccattt tcccattttt cacctatttt 26820 ttccattatt taacaaccaa gactgagcaa acattttcct gttttaattt tcatatatga 26880 aaagacataa gcaaaagctg gatcaaagct tgggcaaatc ctattcaaag tattttccaa 26940 cgtttceatt ccctcgtttg taaagtacaa ttggtaatct taaggcttaa ttaattattg 27000 tgggagattc ataatgtgaa aactaaatgt taagatttgg tcatcaattg aaaaggaaaa 27060 ttaactgtga accccagtct atgcagaaca tccaaagtca ttgcttttac gagatcacac 27120 aggacatcca tatttagaag taagttcaaa tcagaaatcc ccaatccatt ttttcttgta 27180 gttaccactt caagaaccat actccgattt tcgcgacatt gttagttgtt tcagtccaat 27240 ttatgcagat tttgagatgg ttttaacagg tttaacaaat taatttggtt tcttttttaa 27300 aacactcaat ttttatagct ttaacatcat ccatatcaat gggatcattt gttagtatac 27360 gcttactgga catatgaßga gagctttaca agtttctacg tgtatttgaa aaaacgggac 27420 atgtcaggtt aactgcattt ccaatgatac gtcatcagcc tcgcttcgat tcggaaaatg 27480 aaaattatca tttgaaaatg atcaaaccta aaacagattt aacgcatttg cattgttggc 27540 taatgcat to aaaccgggcc tcttccaaaa aaattcacga ctctgctgaa attgttttac 27600 gacgctggaa cgatttcctc aatcccaatt acgcctctga atttacacga atatttgaaa 27660 caccacgagt tgaaggatat gatattttag aatataatgt caaaatttca acggataaac 27720 gcttaggcga cttttcggat ttctccatca ggcagacaat tgaagcagca aaagcagaag 27780 aaattctaaa aattaaccgg acaccaacca tgagaatggt atcacttttt ttcaaaataa 27840 tttactgttt ctattttggc atttatttca gcattctcca ac tccacaga atctcttaaa 27900 acgcggtaaa atgtatccat ttttcaaaaa tttcccatct ccaccacaag ttattccaaa 27960 gaaaacattg gacaaattgg atacaataac agaaataatt gaagaatctg atgcactctg 28020 gacacttatc aaagaatgtt cagaaaattc gaaatcttgg aaatgctcgt caagaaaatg 28080 tgtaagacca tcagttagac atcgatctct tcatggatgg tattcatatg atattcattt 28140 ttctaaattt ttgaatgttg aaagtttttt ttgttcagat tttcaataaa cttttaagaa 28200 AAGA = CAATT ttaaattcta taattcctga atttccaact atgtctatca tttcccaaag 28260 tácatecgaa aaagctcaat aagcaaaacg accacgaaat aacagtatta aaaaaaaaga 28320 cgctgtcatt tgaagttctg gagtgcgatg aaaagtctct cacctcggac tttctgtaat 28380 tacaacatga ttatttagca atttgaccaa ctcgaaataa ggttaagact gaaaattttt 28440 cacaaaaatt ggaacacttg cgaagcgaat tcaagacttt tcgaagttat taaacaagct 28500 ttcaaattct cagtaaaact gaacgttttt tttatgctct ccaaatcatt ttaatatggc 28560 tgctcgcgtc gctgaagtat tttctagagt atgtttaata aaactaatat gtaaatgaaa 28620 aaccaaaaac tcagataaag ageataaett ttataaegea ttttcagaac tettcaaget 28680 aettetatca ttttcagatc gcagta ttct tcttttttcc aaagacacca agaactgaaa 28740 aggttgaagg agcatcaccg gaaatagagg atgactgctt attgttcttc tttttctgaa 2B800 taaaatcaaa tcaaacaccg aaaatatgaa acatatteac taacctgaac agctttcagg 28860 • • tttgatttat tctgatctcc cgccgctgat ctgctctgac ttttgaaacc gggacttgga 28920 gagttaccat tgcgtatgcg agttcgaact ggacgccgat tcttctttct gaataaacga 28980 attatacaaa tttgtatttg aaaacggaca acatacactc cttcttccgc cgaatcgctc 29040 ategaettte tcatttcttg cgttttttcc tggcgttcag gttcaaaagg tggagcaact 29100 ggtttggaca tatacggaag aatgttcgag acctgaatct cttttggttg etcaatatte 29160 tccattgcaa tatgatcggg aagttcaaag tagctgttgg atcctggagc ttgatcaaat 29220 cettegagag ttaaaagttc acgaactgct teaetcattg tgaccctttc ctcttcggca 29280 ccagcacaga ccccataccg aaattgcttg ttgtgttgtt ttactcaaaa gaatagtgaa 29340 caaasttttc tcaccgtaat gaatctgaca atggctggtg gacgttagc ttcaaatggc 29400 attcggtatc cgttctgaae acgtggtaaa acctcagcaa ctttcattcc cggataaggt 29460 tccattccat catggtacac ttcccaacac atgactccat aagcgaaaac atcagtcttt 29520 ggagtataga acccagttct tggaacttct ggagccaacc aectaatagg aactccgaaa 29580 aatttgaaaa ggttggaatt tttgacgttc tctaactttt tgtgaggatt catcegatag 29640 ccatagcctt ctcgtgacag tccaaagtcg gatatettta cttgtccatt cccgtagags 29700 caatttctgg acgcaatatc gcgatgaatt atttgaagtg ttcaagacca aatgaagata 29760 agaccagctt gaagaaccat cgtacgcttc ttggaaatcg gcaacgaacc aatgctcctc 29820 tttagatatg aacccaaagc Cccattgtca gcctaaaata atttacataa gacatttttt 29S8Q cttagtaaaa Caaaactaat cagttaatta attaacatac caactccatt atgaccatca 2994C aaggttcctg tcctgcagcc acaccataaa aagtgacgac attcggatgt ttgaactttc 30000 tcatcaatct ggcttcgtgc atgatttctt tgatctgctc ttttgtcaaa gattccaact 30060 ttgccagctt gattgcagct tttttgacgg tatttcctat gcgaatctet cccaattgaa 30120 cctctccaaa tgctccttct cctaatttct tgattaatgt cacgtcagaa tgttgctttt 30180 cccacggttc acgaccaatt ggacggatga ttacagtttc tgggccctaa aagcaaacaa 30240 atgaaaatsa gtttactcac ttaatttgta agatcacccc agcaacaggt tctttagaac 30300 attgagaaga gatgatagta tctgcgatac tagaaaacca ttttttacca actgcaaact 30360 tgttattgtg ctctcgaatt acataatgac gaatctgaaa taatattctt aaaaattatg 30420 agcaatcgtt ttacgtacgt cctcaattac tccaacatag acagagagaa caaatttcct 30480 tggctctccc acttttggat cagtaaatcg aa ctagaaaa tcgcctcgtt gagtgagcaa 30540 ctgtttcata tcctcacgtg gcaataagee atggtaccag ggttcttttg caagtatttg 30600 c 30601 < 210 > 34 < 211; > 8009 < 212 > DNA < 213 > Unknown < 220 > < 223 > Description of the Unknown Body: Unknown < 400 > 34 ggacccttgg ccacgccatg ggcgatgaaa ttgaccgcgt cgcaacgggC catgtcctgc 60 tcctgcagga agaaggccgc gttcgactcc cgttccgcaa agatcgcgac aaggacattc 120 gcccccgtca ccccggtccg gcccgagctt tgcacatgga tcgcggcgcg ctggatcacc 180 cgctggaagg cggcggtcgg cacggcttcc gagccttcga cttcggtgat cagcgtcgag 240 agatcatcgt cgatgaactc ggtcagggtg gtgcgcaact cgccaagatc gacgccgcag 300 gcscgcatca cgcggctggc gtcgggctcg tcgatcagcg cgacgagaag atgttcgagc 360 gtcgccagtt catgtttgcg cgtgttggcc agcgccagtg cggcgcgaec t? cctgctcg 42C agcgtggtcg aaaacgaagg catgcggcgc tectttcctc gggtctcccg atactggcct 48C catgcgatta agtttcggtg gatttcgccg cgcttcaagg cccggacgcg tcctttctcc 540 acccctcgcc gctctgttgc aaaactgacc agcgcggcgg gctttcgcgc gatccgcagg 600 cagcgcgcga aagtgctttc agaaccggtc cttgcgcgcc cgcgccgcgg tgaagacggc 660 gagcggcgcg gcatccccgg gcaggccgag cgcggcgcgc aacgcagcgt catcggcgcg 720 caaaaaggga ttcgttgccc gttcctcgcc caaagtcacc ggcaaactgg gttccccggc 780 cagccgcaag gccgtcaccc ggtccatccg gtcgtgcagc cgaccgttcc ccggttccag 840 gctgagcgcg aaccggc cgt tcgcggcggt gtattcatgc cccgaacaga cccgggtttc 900 gggcggcagc gcggccagac gggtcagcgt gtcgaacatc tgcqcggggg tcccctcgaa 960 gagacgcccg cagccccagc tcatcaggct gtcgccggaa aagagcagcc ccgccccggg 1020 cagataccag gcgatatggc cgagcgtatg gccgtcggcc gcgatcacct gcgcggcctc 1080 catccccaga tgcagcacgt cgcccggggc caccggatga tcgagcggcg gcagccggtg 1140 ggcaccggcc gcggsccccg ccaccttggc cccggtcgcc tgcgccagcg cctcgacccc 1200 cgcgatgtga tcggcgtggt gatgggtgat caggatgtgg tgcagccgcc agcgccggtc 1260 ggtcagcacc tccagcaccg gggccgcctc ggggacatcg accaccacca cggtatcggt 1320 ggcg cgtcg tgccagagcc aggcgtaatt gtcggtcagg caggggatcg gggtcagttc 1380 qagcgtcatg gccttttgcg catctttcgc tatcctgacc cagcttcgcc caaggaaggc 1440 caacctgcaa tgcatctcga cgtgctcgac ctgcgtgatt tctactaccg cacccaattg 1500 gggcccacgg cgcaaaaggc gatccgcgac aaggtggtcg aactctggcc ggacacccag 1560 tccggcatgg ccgggctgac ggtggcgggc tacggcttcg cggtgccgct gttgcgcccc 1620 tatct GGCC gggcgcggcg ggtgatcggg ctgatgcccg cgcagcaggg cgcgatgccc 1680 tggcccgccg gagagcccaa tgtctc? GTG ctctgtgccg aaaccagccg gccgctggag 1740 accgggatga tcgaccggct ggtggtgctg cacgggcttg aagtctccga c accccgat 1800 gcgccgatgg aggaatgctg gcgcacgctg ggccccggcg ggcgggcgcc gttcatcgtg 1860 ccgaaccggg tcgggctttg ggcgccgcgc gaaaccacgc ccttcggctt tggccgcccc 1920 tatacgatgg gccagctcga ggcgcaggca cgacgggtgg ggtttgccoc cgaacgtcag 1980 gcggcsgcgc tgtacattcc gccctcgcag cggcggttct ggctgcgccc ctcccagatg 2040 tgggaacggc tgggcacaag ggcggcgggc tatctggcgg cgggggccgc gatgcccgag 2100 gtgatcaagc aggtgcattc ggtgcgccgc tcggggcttg gcgcggccgc gcgcaagccg 2160 ctctcgatcc ttgaaggggc gcccaagccg gtggtcgggc ggatgtgagc cgcccgcggc 2220 cgcaagaatc gcccggccgg aaaagcccgc ttccgcggca cctcgccctg cggcggggaa 2280 acgcagcggg gcgggcttcg accctttgcg ctaac actcc gtgccggtgc agaaaatgtg 2340 ccagcctgat gcggattcct gccgccaaga tggttgcgag ggtcttgatg ctctgctaga 2400 cgcaaccccg aatgcggcgt gcgagatcat tttgggcgcc gaggggggcc tctgaatcgg 2460 tgacggaacg attggttccg grgtccgcgt gcggaggcaa aagcatcgga agggtggacg 2520 tgtccg? acc agcttcgatt tccgcagcca ttgccgggcg ttatgccacg gccatcttcg 2580 acctcgegca gg ggccaag ggcatcgacg cgctctcggc cgacgtggac gcgctgacgg 2640 ccgccttggc cggttcggcc gagctgcgtg acctgatttc ctcgccggtc tacacccgcg 2700 aggagcaggg ggacgcgatc gccgcggtgg ctgcgaagat gggcctgtcg gcgccgcttg 2760 ccaacggtct gaaactgatg gcgacgaagc gccgtctgtt cgcgctgccg cagctgctca 2820 agggcctggc cgccgcgatc gccgaagcca agggcgagat gaccgcggat gtcacctcgg 2860 ccaccgcgct gagcgcggcg caggccgaga agctggcggc gacgctggcs aaacagacgg 2940 gcaagaccgt caaactgaac gtcgccgtcg atgaaagcct catcggtggc atgatcgtca 3000 agctgggttc gcgcatgatc gacaccacgg tcaaagccaa actcgcttcc cttcagaacg 3060 ggtcggataa ccatgaaaga atgggcatcc aagcagctga gatttctccg atcctcaagg 3120 agcagatcaa gaacttcggg caggatgccc aggtcgccga agtgggccgc gtgctctcgg 3180 tcggtgacgg gatcgcgcgc gtgcacgggc tcgacaacgt ccaggcg gc gagatggtcg 3240 aattccccgg cggcatccqc? ggatggcgc tgaaccttga agtcgacaac gtcgggatcg 3300 tgatcttcgg gtcggaccgc gacatcáagg aaggcgacac cgtcaagcgc accaacgcca 3360 tcgtggacgt tccggcg? gc gaaggcctgc tgggccgcgt cgtggacg? c cttggcaacc 3420 cgatcgacgg caagggcccg atcgtggcga aagagcgtcg catcgccgse gtcaaagccc 3480 cgggcatcat tccgcggaaa tcggtgcatg agccgatggc gaccggcctc aagtcggtcg 3540 acgcaacgat cccgatcggc cgcggccagc gcgagctgat caccggcgac cgtcagarcg 360C gcaagaccgc gatcgcgctc gacaccattc tgaaccagaa gtcgtacaac gacgccaacc 3663 cgggcaacaa gccgcactgc ttctatgtcg ccatcgggca gaagcgctcg accgtggcgc 3720 gaagctcgaa agctggtgaa cgatggaata gaagccggcg gtcgccgcga caccaccgtc 3780 ccgcctcgga cccggcgccg atgcagttcc ttgcccccta ttcggcgacc gcgatggcgg 3840 aatacttccg cgacaacggc atgcacgcgc tgatcatcta tgatgacctc tcgaagcaag 3900 ccgtggccta tcgtcagatg tcgctgctgc tgcgccgtcc gccggggcgt gaagcctatc 3960 cgggc acgt gttctaCctg cactcgcgcc Cgccgga acg ttcggcgaaa ctgaacgagg 4020 atttcggttc gggctcgctg accgcgctgc cggtcatcga aacccagggc ggcgacgtgt 4080 cggccttcat cccgaccaac gtgatctcga tcaccgacgg tcagatcttc ctggaaaccg 4140 • • aactgttcta ccagggcatc cgcccggccg tgaacaccgg tctcccggtg tcgcgcgtcg 4200 gttcgtcggc ccagaccaac tcgatgaagt cggttgccgg tccggtgaaa ctggagcttg 4260 cgcagtatcg cgaaatggcc gcctttgcgc agttcggttc cgacctcgac gccgcgacgc 4320 aaaagctgct gaaccgcggt gcccgtctga ccgagctgat gaaacagccg caatattcgc 4380 cgctgaccaa cgccgaaatc gtggcggtga tctttgcggg caccaacggc ttcctcgatg 4440 ccgttccggt gaaggaagtc ggccggttcg agaaaggcct gctggcctat ctgcgctcga 4500 cccgcaagga cgtgcttgag tggctcacea aggaagaccc caagatcaag ggcgacgccg 4560 agaagaagct caaagacgcg atcgccgagt tcgccaagac cttcgcttga cggcctgaaa 4620 4 »ggacagggag atgcccascc ttaaggacct caagaaccgg atcstgagtg tcaagaacac 4680 tcgcaagatc acgaaagcga tgcagatggt cgcggcggcg aacattcgcc gcgcccagga 4740 aagcgccgaa getgcecggc cctatgccga gcggatgaac gccgtgatgt cgagccttgc 4800 cggtgcggtg ggctcgaccg acggtgcgcc gcgcctactt gcgggcacgg gctccgacaa 4860 ctcgtcatca ggtccatctc tgacgggcga gcgcgggctt tgcggcggct tcaacgccaa 4920 tatcgcgaaa ctcgcqaagg cgaaggcgat ggaactgctg gcccagggca agacggtgaa 4980 gtcggcaaga gatcctcacc. aaggtcgcga cgcgctgegt cgtgatctgg gccaqtatta 5040 atcgacctga catcgatcac gcgacgtgaa gaaactgagc tacccggcgg cgcagaagat 5100 ttcgcaaaac atcatcgacc gcttcgaggc gggcgaatac gatgtggcga cgatcttctt 5160 cagagcgtga ctcggtcttc tcagccaggt gccgaccgcc tcccggcgca aagcaggtga 5220 gttcgaaacc gatgcggcct cggcctcggc ggtttacgac tacgaaccgg gcgatcagga 52S0 aatcctgacs gcgctgctgc cgcgtgcggt ggccacggcg atctttgccg cgctgctgga 5340 aaacaacgcg tccttcaacg gggcgcagat gccggccatg gacaacgcca cccgcaacgc 5400 gggtgacatg atcgatcgct tgaccatcga gtataaccgc tcgcgtcagg ccgccatcac 5460 atcgaaatca caaagagctc tctcgggcgc cgaggcgctc tgacggaacc ggagatagaa 5520 agcaaaggca gagaatggca aagtgaccca ggtcatcggc gccgtcgtcg acgtgcagtt 5580 cgaagacggc ctcccggcga ttctgaacgc ccttgaaacc accaacaacg gcaagcgcct 5640 cgttctcgaa gtggcgcagc acctgggcga gaacaccgtc cgcaccatcg cgatggacgc 5700 •• gaccgagggt ctcgtgcgcg gcgcggccgt gtccgacacc ggcggcccga tcaccgttcc 5760 ggtgggcaac gccaccctgg gccgcatcct gaacgtcatc ggcgagccgg tggacgaacg 5820 cggtgacgtg tcgaaagccg aagcccgggc gatccaccag cccgcgcccg atctcgcggc 5880 gcagtcgacg gaaagccaga tcctcgtcac cggcatcaag gtgatcgacc tgctcgcccc 5940 ctattccaaq ggcggcaaga tcgctctctt cggcggcgcc ggtgtgggca agaccgttct 6000 ctgatcaaca gatcatggaa acatcgcgaa agtgcactcg ggcttctcgg tgttcgcggg 6060 cgttggcgaa cggacccgtg agggcaacga cctttaccac gagatgateg aatcgggcgt 6120 tatcaacctc cagaagctcg aagaatcgaa astggcgctg qtctacggcc agatgaacga 6180 acccccgcgg gcccgtgccc gcgtggcgct gaccggcctg accctggcgg aacagttccg 6240 • cgaccagtcg ggcaccgacg tgctgttctt cgtcgacaac atcttccgct tcacccaggc 6300 cggttcggaa gtgccggcgc tccttggccg tatcccctcg gccgtgggct accagccgac 6360 gctggccacc gacatgggcg cgctgcaaga acgcatcacc tcgaccaaag ccggttcgat 6420 cacctcggtt caggccatct acgttccggc cgacgaccrt accqacccgq ccccgqccac 6480 gtcctttgcc cacctcgacg ccacgaccgt tctgtcgcgt gcgatctc gg aactcgggat 6540 ctacccggcc gtcgacccgc tcgactccac ctcgcggatc cttgacccgc aagtcgtcgg 6600 cgaagagcac tatcaggtcg cccgtgacgt ccaagggatg ctgcaacgct aeaagtcgct 6660 gcaggacatc atcgccaccc tcggcatgga cgaactgtcg gaagaagaca agctgacggt 6720 ggcccgcgcc cggaagatcc agcgcttcct gtcgcagccc ttcgacgccg cgaaagtctt 6780 caccggctcg gacggcgtgc aggttccgct cgaagacacc atcaagtcgc tcaaggcggt 6840 ggctgcgggc gaatacgacc acctgccgga agcggccttc tacatggtcg gcggcatcga 6900 tgacgtgatc gcgaaagccc agcgcctcgc cgctgcggcg taagggggaa ccatggccga 6960 taccatgcag ttcgatctcg tgtcgccgga acggcggctt gcctccgttg ccgcgagcga 7020 ggtccgtctt cccggcgtgg aaggcgatct gacggcgatg ccgggccatg cgcccgtcat 7080 cctctcgctg cgtcccggca tcctgaccgt ggtcagcgcc gcgggcacgg ccgaatacgc 7140 cgtgaceggc ggcttcgccg aggtttcggg cgagaaggtg accgttctgg ccgagcgcgg 7200 tctgacccgg gcggaactga ccgccgcggt tcatgccgag atgctggccg aggccaagaa 7260 agtcgcggac gecgcgcacc cgtcggtggc cgatgccgcc gcgaagatgc tggccgacat 7320 ggaagcgctt ggctcgcaca tcaatctctg acgggacatc ccgccggata t ctcgggccc 7380 eggceategc gccggggcce ttgctttttg cttttgtctt gccgcgccge atattagcgt 7440 gaaggtgcag gcagccggag tgagcgacag gaacggatga agaagttttc ctcgacccgg 7500 atcggcgtgg cccagggatc gctggtgctg ttttcggatt atctggacgg cggcgtgatg 7560 tggacgggcg to? ggcccgcg cgaattgc? c aggctggtgg tgttcgacga agccttccgc 7620 gagatcccgg cggtgcaggt gtcgetgtcg atgtgggaca tcgaccagaa gcacaatccg 7680 tttccgccga cgcatggaca catggtgacg gccgagggct tcgtgatcgt ctttcgcacc 7740 tggggcgaca cccgcgtcgc ccgcgtccgc gcggactggc tggcgatcgg c gctgcgcc 7800 aatgacgacg actgggacgt ggcctgatcc cgcccggctt gactttccgc ccccccgcgc 7860 cgcgactttc ccatccaacg aggcccgccc gtgcaacaag atgccccccg 7920 ctggcagctc gtggtgatcc tgtgggggac gaaatatccg gtcgccgaac tcaacgccct 7980 gatcgagacc gcgtggcccg ggcctcgag 8009 < T210 > 35 < 211 > 9810 < 212 > DNA < 213 > Unknown < 220 > 223 > Description of the Unknown Body: Unknown < 400 > 35 gatatcgggc ttgtcatttt cgattgcgac ggggttctgg ttgattcgca agttctggcc 60 gtggccgtcc tcatcgcaga actggaccgg gcgggcgtgc gggtcgacga ggccttcgtg 120 catcggcatt ttctgggccg gagcttcccg gctgttcagg aggtcgtgca gcgccagttc 180 ggcgtgaccc tgcccgagac cttccaggtc gaggaacgtg cccggctgct gtcagccttc 240 gagaccggcc tgcgggccat gctcggggcc gcggagaccg tccgcgcgct gtcggtgccc 300 tactgcctcg ccacgtcgag cacgccggcc cggctcacgc gctcgctggs gatcacgggc 360 cttgcggccc tcttcgaggg acgctgcttc accgcgagcc aggtggcgcg cggcaagccc 420 gcgcccgatc tgttcctgct cgccgcggcc gagatgggcg tcgcgcccga acgctgcctc 480 •• gtgatcgagg ataccgagcc cggcgtgcgc gcaggcctcg cggccgggac gcaggtctgg 540 cgcttcaccg gcggtagcca tttcgcgaac cgatcccccg aggatgCgCC cgatgccctg 600 ccgcaccggc ggcccgacag cttcgaccgt ttctacgaga ccctgcccgg cctgcgccgg 660 gccaagtgcg agaccctgac atgatcgacc ggcccgasag cgagccgacg cccctcgacg 720 atgccgcgcg cgcgggctgg ctctattatg tcgcaggcct gactcagqat cagatcgcgc 780 gggaqctcgg cacctcgcgt cagcgggcgc agcggctggt gagccgggcc atetccgaac 840 ggctgatcca cgtccggctc gagcaccggg tctcgggctg cctgcatctg gaagccgcgc 900 tcctccggcg cttcgggttg aagctggccc gcgtggcgcc gagtctcggg tccgaggtgg 960 atcccctgcc ctccatcgcc cccaccgccg ccgccqaggt ggagcgggtg ctgcgctcgg 1020 agcggccgat ggtggtggcc ttcggcaccg gccggtcgct gcgcgccacc gtcgaggaga 1080 ggtctgcgaa tgacctcgat cagcacaaga tcgtgtcgct caacggaaat atttctgcgg 1140 atggctcggc ctcctactac gatgtgatct tccgcatcgc cgaccgtgtg cgtgcgccgc 1200 actatccgat gccgatgccg gtcatcgcgc aggatgcggc ggagcgggag ctgtttcatg 1260 cgctaaagcc cgtgcagtcg gtgctgcggc ttgcgcgcaa tgccgatgtc accttcgtc g 1320 ggctcggaca gatgggcgag gacgcgccgc tcctgaagga cgggttcatc acgcccgagg 1380 agctgaccga gatgcaggat ctgggcgccg tcggagaggt ggcgggacgg gccctcqact 1440 cggagggtcg ctacctcgaa accagoatca atcagcgggt tgcgggcgtc cgtgcccaac 1500 tttccgagga tcggacggtg gtcgccatcg ccggtggcag gcgcaagccc gcggcgcc? c 1560 acgcaggctt aaggggccgt cttttcaacg gcctgatcac cgacgagttc acggcgcagg 1620 cacttctgtc ctgaagccgc cgaaaggcgc ggcaaaaagt atttgacagg ctggcacccc 1680 tcggtgagta atcacccgcc gcacgaaata atgctcaccg tgcaggccag ggaggatact 1740 gatgaccgca agatttcgcg ccctgatggg cgcgtgcgcc gtggctgcgc tctcgtccgc 1800 gaaaccatca cgccggcgcc ccgtggcgac tgtcaacaac ggcgacatga tccgcatgca 1860 ggggc catg tccgagttca acgcgcagca ccccgacatc accgtcgagt gggtgacgct 1920 cgaggaaaac gtgctgcgcc agaaggtcac gaccgacatc gccaccaagg gcgggcagtt 1980 cgacgtgctg accatcggca cctacgaggt tccgatctgg ggcaagcagg gctggctcgt 2040 • • gagcctgaac gacctgccgc cggagtatga tgccgacgac atcctgcccg cgatccgcaa 2100 cggcctgacc gtcgacggcg agctctatgc cgcgcccttc tacggcgaga gctcgatgat 2160 aaqqacctga cacgcatcgc tggagaaggc ggggctgacc atgcccgacg cccccacctg 2220 ggacttcgtg aaggaagcgg cgcagaagat gaccgacaag gatgccgagg tctacggcat 2280 ccgcccgcgc ggcaaggccg gc ggggcga gaacatggcc ttcctcagcg ccatggccaa 2340 cagccacggc gcgcgctggt tcgacgagaa ctggcagccg cagtccgacg gcgaggcctg 2400 gaaggccacg ctgaccgact atctcgacat gatgacgaac tacggccegc ccggcgcctc 2460 gaasaacggc ttcaacgoga acctcgcgcc gttccagcag ggcaagtgcg gcatgtggat 2520 cgacgcgacg gcggccgcct ccttcgtgac eaaccccgag gaatccacgg tggccgacaa 2560 ggtgggcttc gcgctcgccc ccgataccgs caagggcaag cgggccaact ggctcggggc 2640 ctggaacctc gcgatcccgg cgggctcgca gaaggtcgat gccgccaagc agttcatcgc 2700 ccgggcgacc tcgaaggact atgccgagct ggtgg ctcg aaggaaggct gggccaacgt 2760 gcctccgggg acgcgqacgt cgctctacga qaacccggaa tatcagaagg tgccgcccgc 2820 ctcgacagca gaagacgacg tcaacgcggc tgacccgacc cacccggcgg t cgatccggt 2880 gccctaegtc ggtgtgcagt tcgtggcaat ccccgagttc cagggcatcg gcaccgccgt 2940 gggccagcag ttctcggcag ccctcgcggg ctcgatgtcg gccgagcsgg cgcttcaggc 3000 ggcccagcag ttcacgacgc gcgaaatgac ccgcgcgggc tacatcaast gagcccttcc 3060 gcgggccggc cctgagcggc cggcccgcac cgcctgccgc ttccggccgt atccgccgga 3120 ggcctttccg ccccatcagc cccgaggcct ccatggcgac ccagcattca aagactgcgg 31B0 cgcgtctgat gatttccccg gccgtgatcc tcctgttcct gtggatgatc gtgccgctgt 3240 cgatgacgct ctacttcagc ttcctgcgct acaacctcct catgccgggg atggagagct 3300 tcaccggctg ggacaattac tattacttcc tgaccgatcc ggccttcccc gcggccctga 3360 ccaacacgat cctcctcgtg gtcggcgtcc ttctcatcac cgtggtgggc ggggtcctgc 3420 tcgcgctcct gctcgaccag cccttctggg ggcagggcat cgtgcgcgcg ctggtgatcg 3480 cccccttctt cgtcatgccc accgtctcgg cgctggtctg gaagaacatg ttcatgaacc 3540 ccgtgaa gg gatgttcgcc catatcgccc gcgggctcgg ccttccgccg ttcgacttcc 3600 • • tgtcgcaggc gccgctggcc tcgatcatcg gcatcgtggc ctggcagtgg ctgcccttcg 3660 ccacgctgat ccttctgacg gcgctccagt cgctcgaccg cgagcagatg gaggcggccg 3720 agatggacgg cgcctcggcg ctcgaccggt tcatccacat caccgtgccg cacctgacgc 3780 gtgccatcac cgtggtggtg ctgatccaga ccatcttcct tctgggcgtc ttcgccgaga 3840 tcctcgtcac gacgaacggt ggacccggca ccgcctcgac caacatcacc tacctcgtct 3900 atgcgcagcc gctcccgaat tacgacgtgg ggggcgggtc ggccggcgcc atcgtcgccg 3960 tggtgctcgc caatatcgtg gcgatcttcc tgatgcgcat gatcggcaag aatctggacg 4020 cctgacatgt cacgccgcac ctcaacccgc cgcacgetga tcgtcacgct cgccgcctgg 4080 acgatagcct tcctcatctt cttcccqatc ctctggacgg tgctgatgag cttcaaatcg 4140 gaaggagacg ccatcaaggc gcccttcgcc atgctcttct cggactggac cctgcaatc 4200 tacgccgatg tgcaggaacg gtcgaactac gcccgccact tcatgaattc ggtggtgatc 4260 tcgctgggct cgaccctcgt ggcgctcgcc aCcgcgatcc ccgccgcccg ggccatggcc 4320 ttcgtgccgg gccggcggac gaaggacgtg ctgatgtgga tgctgtcgac caagatgatg 4380 ccggcggtgg gcgtgctcat cccgctctat ctgatcttcc gcgacacggg cc tcctccac 4440 acqcggatcg gcctcgtgat cgtgctcacg ctcatcaacc tgccgatcgt ggtctggatg 4500 ctctacacct accccaagga gatcccgggc gagatcctcg aggcggcgcg gatgaaeggg 456C gcgacgctcg gccccgagat cctctatatc ctcacgccga tggccgtgcc GGGC = ccccc 4620 tcgacgctgc ttctgaacgt gatcctcgcc tggaacgagg ccttctggac gctgcagctg 4680 accaectcgc gggcggcccc gctcacgcag ttcatcgcga gctattccag ccccgagggc 4740 ctcttctacg ccaaactgtc ggcggcctcg accatggcca tcgcgccgat cctgatcctt 4800 gccagaaaca ggctggttca actcgtccgc ggcctgacct tcggcgcggt gaagcgagga 4860 ccacatgggc aagataaccc tgcgcaacgt ccagaagcgg ttcggtgagg cggtcgtcat 4920 gacctcgaca cccctcgctc tcgaggatgg cgagttcgtc gtcttcgtcg gcccctcggg 4980 ctgcggcaaa tccacgctcc tgcgcctgat cgcgggcctc gaggatgtgt cggacggcca 5040 gatcatgatc gacgggcgcg acgccaccga gatgccgccc gcgaagcgcg gcctcgccat 5100 ggtgtttcag agctacgcgc tctatccgca catgacggtg aagaagaaca tcgccttccc 5160 gctgcggatg gcgaagatgg agccacagga gatcgagcgg cgcgtgtcga acgcggccaa 5220 gatcctgaac ctcaccaact atctcgaccg ccgccccggc cagctctcgg gcgggca ACG 5280 gcagcgggtg gccatcgggc gcgccatcgt gcgcgagccg gcggccttcc tgttcgacga 5340 gccgctctcg aacctcgatg cggcgctgcg ggtcaacatg cggctcgaga tcaccgaact 5400 ctcgagacca gcaccagtcg cgatgatcta tgtcacccac gatcaggtcg aggccatgac 5460 catcaccgac aagatcgtgg tgctgaacgc gggccggatc gagcaggtgg gctcgcccct 5520 caccctctac cgcaatccgg cgaacctctt cgtggcgggc ttcatcggca gcccgaagat 5580 gaacctgatc? aggggcccg aggccgccaa gcacggcgcc aceaccatcg ggatccgccc 5640 cgaacatatc gacctgtcgc gcgaggcggg ggcgtgggag ggcgaggtcg gcgtctcgga 5700 acatctcggc tcggacacgt tcctgcatgt gcatgtcgcg gggatgccca ccctcaccgt 5760 gcggacgggc ggagagttcg gcgtccatca cggcgaccgg gtctggctca cgccgcaggc 5820 cgacaagatc caecgcttcg gcgccgacgg aaaggcgctc tgacatgcgg ctcgacggca 5880 agaccgccct catcaccggc tcggcgcgcg gcataggccg cgccttcgcc gaggcctatg 5940 tgcgtgaagg cgcgcgcgtg gccatcgccg acatcaacct cgaggcagcc cgcgccaccg 6000 cggccgagat cggccccgcg gcctgcgcca tcgccctcga cgtgaccgat caggccagcs 6C60 ccgaccgctg cgtggccgag cttctcgacc gctggggcag catcgacatc ctcgtgaaca 6 120 acgcg? CCCT cttcgatctg gcgcccatcg tcgagatcac ccgcgasagc tacgaccggc 6180 tgtccgcgat caacgtctcg ggcacgctct ggcggtggca tcatgatgca cgggcgatga 6240 tcgcgggcgg ceggggcggc aagatcatca acatggcaag ccaggccggc cgccgcggcg 6300 aggcgctggt gggcgtctat tgcgcgacca aggccgccgt catctcgctc acccagagcg 6360 cctcatccgc cggggctgaa cacgggatca acgtcaatgc catcgccccg ggcgtggtgg 6420 ctgggacggg acggcgagca gtggatgcga agttcgccga ctacgagaac ctgccccgcg 6480 gcgagaagaa gcgtcaggtc ggcgcggcgg tgcccttcgg ccgcatgggc cgcgccgagg 6540 acctgaccgg catggcgatc ttcctcgcca cgcccgaggc cgactacatc gtggcccaga 6600 cctacaacgc ggacggcggc aactggatga gctgaggccc aaggcccggc cctccccccg 6660 tcgaacgcgc cccctatccg aggtaatccc atgacccgct ccgccacccg tccctcctat 6720 • • gaccgcaagg cgctcactcc cggcatcgtc catatcggcg tcggcaactt ccaccgggcg 6780 catcaggcgg tctatctcga cgatctcttc gcgctgggcg agggccacga ctgggccatc 6840 ctcggcgcgg gcgtccgccc gaccgatgcg cggatgcgcg aggctctggc cgcgcaggac 6900 cggtgatcga aacctctcga gctcgatccg gcgggccacc gggcccggca ggtgggggcg 6960 atggtgggct tcctgccggt cgaggccgac aatgcggccc tgatcgaggc catgtcggat 7020 ccgcgcatcc gcatcgcctc gctgaccgtg accgagggcg gctattatgt cgatgccccg 7080 ggcgcctccg atccgacgca tcccgatatc gtggccgatg cggcccatcc tgcgcggccc 7140 gcgaccgcct tcggcgcgat cctcgccgcc ctccgcgccc gccgcgacgc gggggttaca 7200 cccttcaccg tgatgtcctg cgacaacctc cccggcaacg gccatgtcac ccgcaacgcc 7260. gtggtgggcc tggccgagct ctacgacgcc gagcttgcgg gctgggtgaa ggcgcaggtg 7320 acggcatggt gccttcccga cgaccgcatc acccccgcca ccggcccgca cgagcgcgaa 7380 ctggcgcagg gcttcggcct cgccgatccg gtgcccgtca cctgcgagcc gttccggcag 7440 tgggtgatcg aggatcattt ccccgccgga cgccccgcgc tcgagaa gt gggcgtgacc 7500 ttcaccccgc atgtccatgc ctacsaggcg atgaagatcc gcatcctgaa cgggggccat 7560 gcggcgatcg cctatccgtc ggcgctcatg gacatccagc tcgtgcacgc ggccatggcc 7620 catccgctga tcgcggcctt cctgcacaag gtcgaggtcg aggagatcct gccccatgtc 7680 ccgcccgcgc ccgacaccag catccccgac tatcttaccc tgategagag ccgcttctC 7740 aaccccgaga tcgccgacac gacgcgcagg ctctgcctcg acggttcgaa ccggcagccg 7300 aagttcatcg tgccgtcgct gcgcgacaat ctggcggcgg gcacggtgcc gaaggggctg 7860 gtgctgctct cggcgctctg gtgccgctac tgcttcggca cgacggactc gggcgttgtg 7920 acgatccgaa gtcgagccga ctggacggcg ctgcaggacc gggcgcggcg ggcgaaggag 7980 acgccggccg agtggctggc gatgaccgaa gtctacggcg atctggcgca gaacgatctt 8040 ctggcgsccg agttcgcggc agccctcgag gcggtctggc gcgacggggc cgaggcggtg 8100 ct gcggcgct tcctcgcggc ctgatccgca gggcccagcc gctcggagca ccgaagcgga 8160 gcccctgccc cttgcggcgc accgtgaggc gaaacgaccg ggccaccccg gggccaccgc 8220 ctcggtaaca ccatggtatc gcgcaagaat gccggcgcct ctgccgaacg ggcccggctg 8280 ccgggcgagg cgccggactt gtcaaggcgg cggccctcgg gtagagaggg cgggcgtggc 8340 cccgttagca cagtggtagt gcagcgctct tgtaaagcga aggtcgttcg ttcaaatcgg 8400 acacggggca cgcgatcctc cctccgcatc ggcgctcgcc cccggtctgg actgcctctt 8460 cggaaggcac ctgcccgctt gtgcgccgcg ccctttcctc gcttcccaag cgtctgtcac 8520 ggcttgcgga aagccgtgcg cctcggttct ggacagccgc cccttgcggt gtaatctgcc 8580 ctcagcgcgc agccggcgga cagaagccgg cccgccacgt ccacaaggga ggaatgccat 8640 ggatcgtcgt tcattcatca ccaaggcegc cgtgggaggg gccgccgcga gcgccctcgc 8700 cgcgccggcc cttgcccagt ccgcgcccaa ggtcacctgg aggctcgcct cctccttccc 8760 gaaarcgctc gacacgatct tcggcggcgc cgaagtgctg tcgaagatgc tctccgaggc 8820 aacttccaga caccgacggc tccaggtctt ctcggcgggc gagccggtgc cgggcctgca 8880 ggccgccgac gccgtgaccg agggcaccgt cgaatgctgc cacacggtcg gctactatta 8940 ctggggca ag gatcccacat tcgcgctggc cgcggccgtg cccttctcgc tgtcggcgcg 9000 cggcatcaac gcctggcact accatggcgg cgggatcgac ctctacaacg atttcctcgc 9060 gcagcaceac atcgtggcct tcccgggcgg caacaccggc gtgcagatgg gcggctggtt 9120 ccggcgcgag atcaacaccg tgqccgacat gcagggcctg aagatgcggg tcggcggctt 9180 tgcggggaag gtgatggagc gtctgggcgt cgtgccgcag cagatcgcgg gccgogacat 9240 ctatccggcg ctggagaagg ggacgatcga cgcgaccgaa tgggtcggcc cctatgacga 9300 ggctccttca cgagaagctc aggtggcgcc ctactactac tatcccggct ggtggga = gg 9360 acc cggccc tgttcaacaa gtccatttca gaggggctga gagcgcctac ccccggccta 9420 tcagtcgctg ctgcgcaccg cctgccacgc ggccgatgcg aacatgctcc agctctacga 9480 ctggaagaac ccgacggcga tcaagtcgct ggtggcgcag ggaacccagc tcaggccctt 9540 cagccccgag atcctgcagg cctgtttcga ggccgcgaac gaggtctatg ccgagatgga 9600 agcctcgaac cccgccttca agaagatctg ggactcgatc aaggccttcc gctccgagca 9660 ctacacctgg gcgcagatcg ccgaatacaa ctacgacacc ttcatgatgg cgcagcagaa 9720 cgccggcaag etetgagccc gagcgccgcg cgaaagagga ccccggagcc gcgttcccgg 9780 gtc ttttcat gggcgacagg ggccggcgcg 9810 • • < 210 > 36 < 211 > 1886 < 212 > DNA < 213 > Unknown < 220 > < 223 > Description of the Unknown Body: Unknown < 400 > 36 tgagtgtcta ttttttttcg ggttttttta agtgtgaatc acatggttag gagcagttgt 60 cttcaatgtg accaaccatc ceaaggctet aattcaacgt ttgggtgtgg gggcccgctg 120 gcagctgtgc gtqccactgg gctgttggtg tcggtgcttt actccccctc accgcaaacg 180 gctaattggt cggcacaggg tatttccaca aaggcgctgt atccggcagt gcctgtgcct 240 tccactctgc tgcctggaag cgcgcctgcc aaacaccagc tgcacgtttg gagggcacat 300 gcgatgtcgg aggccacaac aaacaattca ttcaaacagt cattatttgg gtacaatgcc 360 tctggcctca atctccccca gtggccgcca actggccggt ctttctttgc atctggagct 420 ttgatggcag ctgtaacgca acgcaaggag atcgccgtct tctccgcctc gggtcaggct 480 gctgagccgg agggggcgga gcccctgaag cggccttttc cgtctcctgc tgccaaacct 640 aagccgctct tctccacccc ggcaaattcc ttcagcaaca tcttccaggc gcctccatcg 600 ccgcgcacgg actccaccta tggccgaggc ccgcgctcga ccagctt ca c cgacatcaqc 660 aactcgccct ccaacaacgc actccgcaac ccccagtcgg tgat tgacat cgggggagga " 'JO gtcgacttcc tgggggacag aagccctgga aacccgttca cgcggctgcg ggggtccccg 780 AGCT ccaccc tcagcaacct cggcatgggc ctaggcctgg ggctgggcaa gggcaagggc 84 0 ttcggcaagg gcttcggcaa aggccggggg ttccccgtgg aggaggaggt ggaggaggag 900 caggaggtgc tgtcgtgggc cgaccgccgg cgggcgctgg cggaccccga cgccccgccg 960 atgaacgagg acatcaagta cccgcagctg cggctggtgc gggccgtgcc gggcggccgg 1020 gacgagaagc tcggtgtgat gtcgaggcag gaggcgctgg agctggcgga ggcggaagac 1080 atcgacctcg tcctcgtcag catcgacacc gaccccccgg tggccaagct agtcaattac 1140 tcgaagttga agtacgagtc cgagaagaag aagaaggaca gccacaagaa ggggaaggtg 1200 aggagctgaa aaggaggtga ggtgtcccat aagatcggcc agcacgacta cgacgtccgc 1260 • • gtgaagcagg cccgaaagt t cctggagggc ggccaccgca tcaaggtgtc gatggagtt c 1320 aaggggcgcg agaaccagtt cgtggagatc ggccgcgcgg tgatgaagcg cttccagaac 1380 gacctggcgg acatgggcaa ggcggacgcc gtgcccaaga agctcggcac ccggct gat c 1440 ctgaacctgg ccccggccgg ggaggcgctg aaggtgattg cggagcggag ggcagagcgc 1500 gacaggaaag ccgcggctga ggaggagggg gagggcgacg acctcgact t cgtggacgag 1560 aacgaggacg aggatgtgga gggggagggc gaggaggaag aggccgagga qctggaggag 1620 gagacagcgg aggggacgga gg-gccaacc cgcagctgat cgccgatccg cgggggacag 1680 ccacct cccc cccggcctcc ctgccggggg ccggcaccat ccqtcgttgc ggtgcggcgc 1740 tgccatcaac ggccgtcctt gagtttaatg ctcccgccct ccgttggccc gcqqcggtcq 1800 t gct pcaggt ggcctggctg cccgcagctc ctcccctccc cgactgacar agtgtggatg 1860 accgtgatgt gcgccttttc gccttc 1886 < 210 > 37 < 211 > 3015 < 212 > DNA < 213 > Unknown < 220 > < 223 > Description of the Unknown Body: Unknown < 40C > 37 ccgctcacct ccaggccccc ctgagtgcgt acccgagagc gaaasaaaca ggcaagtaga 60 cagatacagc accatggcct ctaggctcgt ccgtgtgctg gcggccgcca tgctggttgc 120 agcggccgtg tcggtcgacg cgegcttcgt ggtgcgcatg gtgcaggcgg tacaccgcca 180 cggcgcgcgc agcgcactca tcgacgacaa atttgtggca cacgacggag ccctgtaccc 240 gtgcggcgag ctgaccggcg agggtgtcga gatggtccgt gctatcggcg agtttgcccg 300 cagccgctac aacaacctct gagccctctc cattggtgga ttcccgtcga cgcggtacaa 360 ctcctctgtc gtgcacacac gctccaccca cacccagcgc accatccaga gcgcgaccgc 420 ctttctgcgc ggcctcttcc aggacgacta cttctacceg gtggtgtact cgaccaacag 480 aacgaccgaa acgctgctca gcactgacgc ggtgccgtcc gtggtgggcc gtagctggct 540 cgacaacccg gcgctgcacg ccgccctcaa cccggtgatc gatgagcacc tcagctggga 600 • • cgccatccag agcgctgcca aggacgcatg ggtcgagggc ctgtgcgcgg actacaacgc 660 ccgcaccaac tgcgtcctcg acatgtacga cgtggccgcc gccttcgagg ccgccgggcg 720 t ttgacaat gccaccaatc tcaaggcggt gtatcccggc cttcaggagg tgaacgccgc 780 tatgtcttca ctggttcaag gctggaacca ctcgatctca cacgagcaag cgcagggctc 840 cgcetcgcag aaccttgcgc agacggtsct ggccaacatc aacgcccacc gcctctctcc 900 gtcgtacaac atgttccagt acagcgctca cgacacaacg gtgactccct tggctgtcac 960 gttcggtgac cagggcgaga cgacgatgcg tccgcccttc gcggttacca tcttcgtgga 1020 gctgctccag gacaccgcag atgccagtgg ccggtacgtg cgcctcatcc gcggcaaccc 1080 tgtgaaggca gccgacggca cctatgtctt ccaggagtct ggtatcaagg catactgcat 1140 cgatgaagcc gggaacaagt acctcgcaca caccggcatc tgcccgctga atagcttccg 1200 ccgcatggcc gactactcgc gccccgccgt ggctgacggc cactqcgcca tgacacagac 1260 tcagtacagc aacatggatt gcccgcgcac tatcgcggac aacaagccgg tgccgtcgcg 1320 ctgctggctc taccgccacg tttgccctag caaggcatgc ccggacagct acattctctc 1380 cgcggtcgac caccagtgct accccgggcc cgacgttacg aaccccacca gcagcagcag 1440 accaccacca cagcgagggt gcagcagcga gggtaccgcc accagcagca gcgaccttac 1500 caccaccagc agcagcgagg gtaccgccac cagcagcagc gacgctacce ccagcagcag 1560 cgagggtacc gccaccagca gcagcgacgc caccaccagc agcagcagcg acgctaccac 1620 agcgagggta caccagcagc cagcagcgac ccaccagcag GCAGCA gctaccacca gcga 1680 cgctaccacc accagtagca gcgagggtac cgccaccagc agcagcgacg ctaccaccac 1740 ggtaccgcca cagcagcgag ccagcagcag cgacgttacc accaccagca gcgagggtac 1800 cgccaccagc agcagcgacg ctaccaccac cagcagcagc gagggtacca ccagcagcag 1860 accaccagca cagcgacgct gcagcgaggg taccgccacc accagcagcg acgctaccac 1920 agcgagggta cagcagcagc ccaccagcag cagC3gcgac gctaccacca gcagcagcga 1980 cgttaccacc accagcagca gc agcgaggg taccgccacc agcaggagcg acgctaccac 2040 cagcagcagc gagggtaccg ccaccaccag cagcgacgct accaccagca gcagcagcga 2100 gggtaccacc agcagcagca gcgacgctac caccagcagc agcgagggta ccgccaccac 2160 •• cagcagcgac gctaccacca gcagcagcag cgagggtacc accagcagca gaagtgacgc 2220 caccaccagc agcagcgagg gtaccgccac caccagcagc gacgctacca ccagcagcag 2280 accaccagca cagcgagggt gcagcagcga cgctaccacc agcagcagcg agggtaccgc 2340 agcqacgcta caccaccagc ccaccagcag cagcagcgag ggtaccacca gcagcagcag 2400 cgacqctacc accaccagca gcgacgttac caccaccagc agcagcagcg agggtaccgc 2460 agcgacgcta caccagcagc ccaccaccag cagcgacgtt accaccacca gcagcagcag 2520 cgagggtacc accaccagca gcagcagcag cagcagcaaa agcacaagcc caccggaCgc 2580 cccccccttc aaaaagcccg cgaactggag cccgcgcgtt ccctcgccgc aaaggggccg 2640 ccacactgcc ggggacatca tccgccgcgt gacgaacggt gttacgat cg gtgcgggtgt 2700 gatgagtaca ccgaaagcac gccggcaccg ccaacagtag cacaacggca tgtaactctt 2760 ttgtgcatgt tt gaatggag aggaggctt c tgtacagcgt acattgt tt c gagaaggtat 2820 cacaaccgct cgtttcaccc ccgtcatctt t tcattttga tctccgtcgt ctcatactgc 2880 ct ccqtgggc tctctctggg tgtgggcgct tgtgcgtgtg tcgctgtaaa gccgttgacg 2940 ccatcgctct tacctgtggg ctattt ttt t aattatggtt tat t attact tccctctctg 3000 cgcgtccotc t gcag 3015 < 210- > 38 < 211 > 38186 < 212 > DNA < 213 > Unknown < 220 > < 223 > Description of the Unknown Body: Unknown < 400 > 38 gatccttcct gcctcttccg gcgtctgggg ccccaggcgc ccttggcttg cagattgatc 60 tccctgatct ctgcctccat ctgctcacag ccttctcccc tgtgtgtctc tgtctcttct 120 tgtaaattca tccgtcgttg gatcagggcc cacccggttc ctcgtggcct cgccttaact 180 gggccatgtc tgcagagacc ctatttccac ataagg cct attcacaggs accgggggtc 240 aggatgtcag cctgtetttc tgggagacgt agttcaaccc acaacacaca tcaaacagtt 300 attgagcgcc gactgcgtgc cctgccgtgc gcttgaaggt cccaccctca ggaagcgggg 360 •• cctagggatg gcggccgtga tcacgcaggc agcagagagc agcrctggga agcggggagg 420 gacgaggacg gggaggcgac atcagcaagg ccgtgtgtga gccaggcagg gtgtccccgg 480 tgtagcacct ggctcgggca gaggccccga ggaggggctg gaggagctgg gcgaggaggc 540 gggcaggacg ggcctgacac tagggacccc gggccccggg aatgcctctg ggsgggcgcg 600 tacacccgtt gctcccagga ggcacacacc gcggttcgct tcgccaagaa tgtttaattg 660 ctacggtttc catttgatga cattcattca tttgtagaga tataacactc agaccacaaa 720 ATGC = taaaa tgcggtggct tttagtacta acagagtgct gcacccgáta ccacagcctc 780 actccagaac attctcatgg gcccaaaagg agacctgggg tgttagtcac cagctcactc 840 gcccctggca cccgtcccca acccacgcta cttagtcatt atttaggtgt ttagqagttg 900 caaagtcaaa tctttaaacc cacatatggc caggcgtgqr qgctcacgcc tgtaatccca 950 gcaccttcag aggccgagac gggcagacca cctgaggtca ggagttcgag accagcctgg 1020 ccaacatggt gaagccccgt ctccactaaa aatacaaaat tagccgggcg cggtggtggg 10B0 cgcctgtaat cccagctact ctggaggctg agacaggaga atcgcttgaa cccaggaggc 1140 ggcggttgca gtgagccgag attgtgccac tgcactccag cctggacaac agagcgagac 1200 aaaaaaaaaa tccgcctcaa agtaccaaaa agtgccccag gtcataaggg cacagctcga 1260 ctaaagggaa tagctggtcc cgtggtgtaa ccaccacaca gaacgaagcc ggaac? TTCC 1320 c ccgtcctt agaagctgco 'tttgctaagg ggaattgccc tgact t ccc = caccatcgac 1380 tcatctccag acccttggtt ttcatgttga tttttcaaaa atcacctgac agtctsaccg 1440 aatgtagctt tccactggtg tgtgtgtgtg tgtgtgtgtg tgtgtgtgtg tgagagagag 1500 atggagtctc gccctgtcac ecgggctcca gtgcagttgt gtgatcttgg ttcactgtaa 1560 cctcctcctc ccgggttcaa gagactcgtg cctcagcctc ccgagtagct gggattacag 1620 gcacccgcca ccacacccag ctaatttttt gtatttttag tagagatggg gtttcaccat 1680 ctggtctcga gttggccagg actcctgaca tcaggcgatc cacccacctt ggcctcccag 1740 agtgctggga ttacaggtgt gagccaccac gcccggcct t atttttcccc cattttettt 1800 tttttttttt ttgagtcagg gtcttgttct gcgctcaggc tggagggcac tggtgtgggg 1860 atcacggctc actgcagcct cgacttcctg caccaccacg cctggctgtt tttttt ttt t 1920 • • ccggtagaga cgggggtctt accgtgttgc ccaggctggt ctagaactcc tgggctcaag 1980 cgatcctccc gcctcggcct ccgcaaatgc tgagatcaca cgcgtgagcc cccgcacccg 2040 gcctcctttc caccgctctt gtctacagcc gcccctcctg gtccgat tgt at tcgcagat 2100 gtcgccaat to cggtgtcaaa cggcgaaggg gcactgagcg ttttttctt c ctcccgtcct 2160 tggcggcagc agctcggttc cggctacggg gctgagcccg tctctcagac gaggaaactg 2220 gggtccgaga ggtgagccgg tcccagaggc agggcgaggg ggaagcggga gtggggt ccg 2280 cagcggaccc agccctgccc cccccctgca ggagatcgtc aacttcaacc gccggaagct 2340 gccggcctcc at gccgctgt tegccaacgc cgaccccaac ttcgtcacgc CCAT? CTGAC 2400 caagctcaag ttcgaggtct tccagccggg tgactacat c atccgcgaag gcaccatcgg 2460 gaagaagatg tacttcatcc agcacggcgt gqtcagcgtg cr cactaagc qcaacaagga 2520 gatgaagctg tccgacggct cctacttcgg gggtgagctt gaggggggcg cgcctggagg 2580 gggagggggc acgcgacccc cgcggtgtgc agagccaggg ggccggggcc ggggccgggg 2640 ccggggatgg ggatggggat ggggatgggg ccggggatgg ggatggggat ggggatgggg 2700 ccggggatgg ggatggggat ggggccgggg atggggatgg ggccggggat ggggccgggg 2760 arggggccgg ggatggggcc ggggccggca ccagggagag cctgggtggg aagcgcccac 2820 gctg ocaag gtgcagaggc cgggccgtgt gcctgggcgg ggagggccgc ggcgcccqcc 2880 tcgceeagca acccccccct gcgcgccacg tgcagagatc tgcctgctca cccggggccg 2940 ccgcacggcg agcgtgcggg ctgacaccta tattcgctga ctgccgccte gcgtggacaa 3000 cttcaacgag gtgctggagg agtaccccat gatgcggcgc gccttcgaga cggtggccat 3060 cgaccgcctg gaccgcatcg gtgagcgggc cgggggcgtg gccggggcgg gtgccctggc 3120 gggggagggg cgtggccaag gcatcaggag agtggcttgg acagtggcag ggggaagggc 3180 gtggctgtgg catcaggggc acggttgggg cagagacgtg gccaaggcat caggagtgtg 3240 gccat? GCAG caggggcgtg gctggggcag gggcagcggc tggccgctcc taggacccct 3300 ttgggtctag aggctgattt tctgacctat tgtcctactt cagccagagg cagcctgttt 3360 cccaagggag ggaatgcaca gggtgtttgc ggttgtgccg aatgctcggt gagcacetgc 3420 cgtgtgctgg gggtgcaggg gacagacccg ggggcccact gggaggctta cagactccca 3480 •• tggactggtg atgaaatcac acacgactgg gctgtgtgcc agcagggcag gtggggccgg 3540 tgggcccccc tgagttggga atgcagagtg gagaccaggg taagggatgc catgtggaaa 3600 cggggaggaa gatgcgttcg cggagtggac acagcacatc ccaaggccct gaggtggaaa 3660 agaggcctag agtccagaga gccagggagg cctggaggag gttggggaag aaggggaggc 3720 cagacacaca gggcccagtg ggcggcaggg agagcttaga ctaaatcagg agcatcaggq 3780 agccatggag ggttctaggt gggcggagga ttgtatccgc cctggtcaga caa? Gcgggc 3840 cgtgtccagg agggagacgg cgacccggcc tctcaggggg gcagtctctg gggcagggag 3900 cggcagagcc ctgatgactg gatgtaggcg ccagagagat ggcggctcat gctgctgttc 3960 gtgggaatgg gaatgaagac catggctgaa acgcaggaca ggtgcgacgg agt? qtgtca 4020 gggagctccc tggtgtacag taggaagctc tccacaactt gctctataca gt agtatgc 4080 aaccccttcc tgagtatcag gtgcttaggt tataacttct gtatacagca ggtgctcagc 4140 acagcctgtg tacaggcagg tgttttcggt atgcctgtgg cacactggag gcagtcatta 4200 cataatcagc gtatacaggt ggtacacatg catacttggt gcacagtgat acctgctcca 4260 tgtacacagc agqcattaaa tacctgttta ctgccaggcg cggtggctca cg cctgtagt 4320 tcg'gaggcca cccagcactt aggtgggtgg atcacgaggt caggagattg agaccatcct 4380 ggctaacatg gtgaaacccc gtctctacta aaaaaaaaat acaaaaaatt agccgggtgt 4440 ggtggcgggc gcctgtagtc ccagctactc gggaggatga ggcaggagaa tggtgtgaac 4500 ccgggaggtg gaccttgcag tgggccgaga tcgcgccact gcactccagc ccgggcgaca 4560 ccgtctcaga gagcaagact aacaaagcaa aacaaaagcc ctgctttctg tatgcaggtg 4620 cttcatgcat gctggctgtg catagcaggt gctcagcctg tatatggcag gtactcaata 4680 tccatactat aggccagaga tgctacatat gtgcctattg tatacagtag gtggtaaatg 4740 catgcttgct ctacacggca agcactgtgt gcgcacccgc ggtgcagagt aggcgcccgg 4800 cgcccgctgt acgcagcagg cgctccctgt gcacacgcta acgccccctc tcccgcaggc 4860 aagaagaatt ccatcctcct gcacaaggtg cagcatgacc tcaactcggg cgtattcaac 4920 aaccaggaga acgccatcat ccaggagatc gtcaagtacg accgcgagat ggtgcagcag 4980 gccgagctgg gtcagcgcgt gggcctcttc ccgccgccgc cgccgccgcc gcaggtcacc 5040 •• tcggccatcg ccacgctgca gcaggcggcg gccatgagct tctgcecgca ggtggcgcgg 5100 ccgctcgtgg ggccgctggc gctcggctcg ccgcgcctcg tgcgccgccc gcccccgggg 5160 cccgcacccg ccgccgcctc acccgggccc ccgccccccg ccagcccccc gggcgcgccc 5220 gccagccccc gggcaccgcg gacctcgccc tacggcggcc tgcccgccgc cccccttgct 5280 gggcccgccc tgeeegcgcg ecgcctgagc cgcgcgtcgc gcccactgtc cgccccgcag 5340 ccctcgctgc ctcacggcgc ccccggcccc gcggcctcca cacgcccggc cagcagctcc 5400 acaccgcgcc tggggcccac gcccgctgcc cgggccgccg cgcccagccc ggaccgcagg 5460 gactcggcct cacccggcgc cgccggcggc ctggaccccc aggactccgc gcgctcgcgc 5520 ctctcgtcca acttgtgacc ctcgccgacc gccccgcggg cccaggcggg ccgggggcgg 5580 ggccgtcatc cagaccaaag ccatgccatt gcgctgcccc ggccgccagt cegcccagaa 5640 gccatagacg agacgtaggt agccgtagtt ggacggacgg gcagggccgg cggggcagcc 5700 ccctccgcgc ccccggccgt ccccccccat cgccccgcgc ccacccccat cgcccctgcc 5760 cccggcggcg gcctcgcgcg cgagggggct cccttcacct cggtgcctca gttcccccag 5820 ctgtaagaca gggacggggc ggcceagtgg ctgagaggag ccggctgtgg ag ccccgccc 5880 gccccccacc ctctaggtgg cccccgtccg aggaggatcg ttttctaagt gcaatacttg 5940 gccccroggc ttcccgctgc ccccatcgcg ctcacgcaat aaccggcccg gcccccgccc 6000 gcgcccgtcc cccsgtgacc tcggggagca gcaccccgcc tccctccagc actggcaccg fcOóO agaggcaggc ctggctgcgc agggcgcggg ggggaggctg gggtcccgcc gccgtgatga 6120 atgtactgac gagccgaggc agcagtgccc ccaccgtggc cceceacgcc ccattaaccc 6180 attccgcgca ccacaccccc ataaacgaca gcattggcgc caagcctggc cgcgtgtgat 6240 tgcccgagac ccgcagggcg tgcacccttc ctgaagacag tggctcctgg gggtggcaaa 6300 agagctttat ttacacactg acaaggctca cggggtgtca gctgaagaag taggtggaac 6360 gcttcacctg ctccaggtcg aaggcccctg cggaggaagc agagcggacg gcgtgggtgg 6420 cgggaaagcc ccgccctggc ccgcagttcg agccaccctt gcgaggctgc ccacccgcct 6480 acctggcttg ggcaccgcct gcagtgtctc cttcagctgg ctggcctcca agatcttctg 6540 gggcctg gg ttggaagcag ggtggggtga ggctgaggcc aggttttggg gtggggggsg 6600 •• gttggggtca aatccaggta gggagcgcct tactcagage agaaccgctt gaccaggaat 6660 ctggacaggt cctgcaggat gggctcgctg tgcaagcgga caaactgctc ccggcacacc 6720 tgggcaggag tcagaggatc cccaggggtg atcaggcagg ctctgggcac cacccctacc 6780 caacgcccca gtgtgggggc cccacccatg ggtggactga ggctcagact acgggggcac 6840 ctggttcatg acggagacat cagccgcgtg agtccagtaa cagagacgaa cagtcgtgca 6900 ggtcaggccc ttcctgtggc agagcggagg actcctgaag ggaggggagc tcacagggce 6960 acccagtgac cagcatcctq gccctgcgct cagccccctc caettgaggt ccagggaagc 7020 ccaccctcct gcaggcctcg ccccacccct cgccccgccc ctccccaaac atcctgggtt 7030 aggtatcagt acagggggag gaaatgttec cagaagcctc ctcgccccac ccctgcegcc 7140 ccccacgctg ctgtgggagc ctcagctccg agggcggcta cgaggtccec tcctgccagg 7200 gccaccaccc cgcatcctga gcattcccag ctcccgtggc cggtagattc tgctggaacg July 60 acctccacgt gctccagatc taaccacaca tcgcggtgcc aagaaacccc cagcaggaag 7320 gggcagcgcc catgctcggc tctccctgtc gggccacagg aggggagctg ccaggaccac 7380 ctacacccgg ggcacacagc ctcagggcct ctacacaggc cccacagaca cagcagatcc 7440 actctgocca gtccctgccc ccagctagac ccagccttgc cagctgtgcc ctgctagcca 7500 gaagacgccc ctgggaggcg agcggcaccc acgccgtccg gagacgcccs. cctgtagcag 7560 tgcagggcgg tgagcatcat gtgggaggag tccagcgagt ggatgaagtt gg egggaag 7620 ccgttcttct gcctacgtgt gttgggcttt ctgaggacgg aacaggcgcc ggtcggggcg 76S0 gcccagggac acccctaact ggccgctgtc tccaccgtgg ctgctctcca gacccccggc 7740 caggccccag cccgggcccc ccactcaccg gctgatgtct ccgttgtggg tgcaggtgat 7800 gctctgaatt ccacctccta tttgctaaaa aggggaaggg gccggtgagt cccacccgag 7860 gcccagcacg gtggtggtac attgaggtgg tggtacactg gggtagtggc acgctaggat 7920 tggcgcggga ggtggcacac tggggtggca cactggggcg gtggtacact ggggtggtgg 7980 tacgctgggg cactggtaca ctgggacgct gttacactgg gatggtggca cactggggag 8040 ggatggggtg gtacactgac cttgaccttg gagtccaggc gatagggctc gatgacgggg 8100 acgcccaggg gtgtgaccca ctccaccaca gagcccatgt gggagacgag gcgggcactc 8160 •• tcggtcagcc agtgctgtgg gacacaggcc gtctcagggc agggggctca ggccggggat 8220 cccgtccact tgcttaggga gtcctggccg agcggggaca ggacaggacg tacctggatg 8280 gcccsggtcc ccgagaacat ctcttgaaga ctcctgtaga gagatagtga cctggcgtac 8340 gaggcctccc acacgaactc ctgcagaggg cgggcagcag gtgcaggtcc tcaggggctg 8400 gccccttcac gccctactcc cccctatctc agagccactg aggcccaagg cctagggcct 8460 agcacggggg caggggaatg gggcctggcg cccacgcagt cagcaagaaa cgeccaagcc 8520 ctaacaggca gccagtggtc tgggggagca gccagggctc ctgctgggac gctggqtcgg 8580 gggcacaccc gtctgagttt taaatggcag tgaaaccaac gtgttcgcag cccgacatgc 8640 ctggcgcacc tggggaaagt cgctcagctc ccggaggcge ttctcaatct gcaggcgccc 8700 gccatagcgc gtgaccccgt acaccaccgt catcaccgtc tgcttcacea ccttgcgggt 8760 gatgaaacct tccagcacct gtgccacccg catgccccgc tgggcgtcct gcctacggaa 8820 cacctccacc tgcacggcgg gtgggccggg ggcgcgggtc agccccgcta gcagcccagg 8880 ggccaccaag cacccatgaa gcceccgccc cagccccacc acatcctcag gacaggccaa 8940 ggtgagggca cctggggccg agactcaggq ctcacattgc ccccacgccg ag atgccccc 9000 gggcagcagg gcacacccta cctgcgcggc cacgccgccg tacacgtcct gcggcacetc 9060 cgagggctcc aggttgacgg aggcggcgcc cacgetgtcg cggcccagag cagcataatg 9120 ctgcaggccg ttgcaagagc cgccctgagg aaggggcggc aaacgggaca cggaagctag 918c agaggcagag acgcgtggga ccccaaacca ccccccaggt cgagccgttc ctagqgccgc 9240 gccaagtgca gcacccccca ccggagcccc cgcacgctcc cgggagagac caggagccat 9300 cactctagga ggctcccgca ccacctccag agaataccac gagcgaaggt gaaatctcac 9360 accctcaagt cgagccccag gcccagtgca cactgcacgg cctcgggggc cagacccagc 9420 tggctcacct gatggacggg gaggtgggag acataggcgg ggcgcgcaca cagggtcgga 9480 cctccataca gcgttcgcca gcaggccagc gtctgccagg gttcctccgc gcccatccac 9540 cctgcgggga cactttcggc cagcggatgg ggggcagtga ggcccgggcc cgatccctga 9600 gcccgctggg aggctgtgtt gcggggaggt gggaaatggg gaggagacgc acacccgtga 9660 tagtgaacac gggacgcatg tgggcgagag acggggcggt gttctccata ggctggatga 9720 • • gccacggatg gaggatggga gctgcgggtg gaccgggctg aaacaagcgt gtccggagct 9760 gccgggggag gagggtggac agaggacctg ggggcgccgg gggaggaagc agctcggcgg 9840 atgcagggga ggggggaacg tggggaacgc gggggccctg gaagggagaa gggcagggga 9900 gcaggacggg cagggggcgc ggsggaggag agcgggcggg ggacgcgggg gcgccagggg 9960 agggggaggg gaggaggaag acgggcaggg ggsgccaggg gagggggagg ggaggaggaa 10020 gacgggcagg gggcgcgggg gcgccggsgg agggcgcggg ggcgccgggg gagggcgcgg 10080 gggtgccggg agggcgggga atgcgggggc cccgccccta ccgtcaaggg ttggtccgcg 10140 gagtccagga tgtcatccat cacctcctcc gcaaaggcca ggcgcttccg cagcggctcc 10200 cgcttcttca accccgtgag attgaccagg tggatcttga gccaatccag gccgtgcggg 10260 ccgagcgggc ggccctgggc gaactccagc agggcccgcg ccacgtcgct gcccaggtgg 10320 ttgaagtgcg gcgggcaggg gtaggtscgg ccgcggaagt ccatgttgtg cggcagccag 10380 aagacgcggt cccgcaggtg CTGC? ccagc gagaggeggt acagcgcctc cgcccgcagg 10440 ctgtgcatct cccgggccac cttctggcag tgcgccagct cacggcgcag ctcggccttg 10500 cgggcgggcg cggcgccgCg cggcaggCgg gcctcgggcg GCT ggggcgc ctcggagggc_10560 ggggccggca cgcctagctg ggggcagccc ttggcctgga agagctgcag caccaggtcc 10620 agcacgcgcc cgtcgacgsg ccaggcgcag ttgcccagtt gggtgaggcc gtccagtgcg 10680 ccatgcagcg cggtgggcgg gcaggtttcc agcagctcct ggtgctgcgt ggcgecttcc 10740 accgtgcgca tcagcttggt ggggctgagc aggaaagcac cagagtgcgg cgatgtccag 10800 ggcagcgggg ggcaaagcat gggtacatcc accgcctcga aggtcagcgt gggctccgcg 10860 gccttctcca gcagctgcac gtaggccggg tgcggcttca ggatgccgat ctggggtgcg 10920 acaggcagac gggtcagggc cccggtgctg gggctttcct gttcccaccc cttaaacttg 10980 ggtgagaggg gccggctccc cggccaacaa gaaaccagtg tggcctccca cgaacagaag 11040 ccacctccag aaacggccgg acacctgcat ggacacccat ggtgtgtccc gagtcctggg 11100 aggtactgac ggctgcgctg agatcaaggc tccgcccaaa ggcgccaacc ccatggggtc 11160 cctggtcctc ccagcgggat gccccccagc tcaggagggc actgcctggc acctgctgga 11220 cgttgcggaa ggaatacacg tggtagagca cggggacaag ccgagaggaa cgatgcggct 11280 tgtccaggct gcatggcatc tgcgtagcct gcaccagcat ctccgccagc agcttgccca 11340 gctccatctg cactggcagg ggc cagggct gctcccgcag ggcctcgggc gcccccagct 11400 cctcccagta ctgccgcggc aggcagggct cgggcacctg taggacaggg csgtcagggc 11460 gctgggcacc ggggcccccg agctagatgc cccaccgccc gtgcctgacg cccggtgggg 11520 cccaagcaca tgccag cagatgaaca gactgaagct tgggtgcaaa cccggctgct 11580 ccagggaggg agagcgccca cccaccactg gccccagcca ggaggagagg gggtgcgagc 11640 ctc = cctcgg cgtcggaggc cagcaagcag aggtacttcc tgtagtggtt ctgcagcgcc 11700 tgcacctggc cactgacccg ctgcctctgc accacgtgcc ggctgaaagt gcgcgcactc 11760 agctcccqgq ccagggtggt gaaggactca ccttgggcgg gcagcgcctg caggacctgc 11820 ggaaggcagc cgtgagtgcc tgcccgcccc gcccggggac ccggccgcgc ggaggaagac 11880 gcacctgcag gagcgc accacctcgc gctcgtccag caggcacagg aaggggtaaa 11940 gtgagaaccg gccctcgtac acctcgcgct ctaggcggtt cttggtctcc cgcagcgccc 12000 ggcacagcgc ccccccccac ggccccgca gggtctccag ggtcttccgc tgcgggggat 12060 gaacgggccc ggtgagcccc gtggcagctg gtgggaccca ggctcacagg acgggggtca 12120 ccgcagctcc ctgcagagac ctgccc tcaasgtccc tgctgtgtgt tccgggtagc 12180 tcctcacccc ggcctgccct ctgccggctt cagcgtgcct gacgcagcca agagcaaaag 12240 cccagctgca gtgtgcgcag aagcacaggc caagacccaa cctcgggacc ccacaagt tt 12300 tccctgagcg gcagccaggc tgagttccta ggccctggaccagacca gggagc 12360 aattcaaccg cacgga gctcagcccc tgcggcggac acgcgacccc ggctcagccc 12420 ctgcggcgga cacgggaccc eggctcagcc cgtgcggtgg acacgcgacc ccggctcagc 12480 ccctgcggcg gacacgggac cccggctcag cccctaccgc gtgcttgacc tccttgcttg 12540 gcaacgtggg cttctccacg gacaccacgc acaccctgct ggccagctcc atgtggagct 12600 gcttctcaaa gaggcactgc agggtcttca agggcaggtg cagcttcggg taggacacac 12660 gccccg cagggatggg ggtagtgagg ttgggggctt gccagagggc gacctgccct 12720 cccaggaccc cgagacagca tgggtgcacg cgtttctgcg tctcctgcaa gttgctggtg 12780 gcgctg acgcggggaa aggcgggctg cggstaaagt cagtgccagc agtgcaaacc 12840 • • aaaggccttg accctcctgg cctcgacccc tctagaaggg acactgggca ccgtgcaggg 12900 ggtggcaggg gcggcgatgc tgggagctgg cagagcctgg ggagaccgtt cactgcaccc 12960 ccagatgttg gctgctttct cctcaaactc agaactgtat gaacgtgacc catccagaaa 13020 tagatgaatt aaaaataaca actaaagcct agcgctttga gaatcaaaga. cgcacgtcca 13080 cataaaagct tgtacacaaa cgttcacagc tgcatgactc agcagaaaca gcagtcgata 13140 gcccaacgtc ccataaasgg acgaacagac gggcacggcg cggccatcca cgcaccggag 13200 catgactcag ccctgaccca ggccgccCcc cggaggcacc atgaggacgt cacgctcagt 13260 gggagatgcc aaacacaaaa ggtctcgcag cgcgcggtcc catttctatg gaacgtccag 13320 agcagactca tccacagatg gggaccggat ggggagtgac ggggatgggg acgaggcttc 13380 ctttcagggt gaCggaacat tctagaatta gacaaccgtg actacaccaa aatcgccgaa 13440 ttacaccttt aagagggttt tatggcaggt gaattacacc teagtasca acgagcccac 13500 tgcgtgcacc tggcagcccc actcaaacgc actgccctcc tgtcacccca ccctctctct 13560 gcggcccccg accacctcgt ccccccgagc ccacaccctc agggccaaga ccctcccagc 13620 tctgggtcct cccatcttct cagaggagga agggaggaat tcagggccca gcccaggtga 13680 gccctgggca ccggggaggc ccattg? TCT gagctgaggc tccaggaacc cccaaagggc 13740 agctataagg actgaagtct gccggggccc acgtgggctc accttggcac acacgtccct 13800 gagc = gcttg gaggtgctga ccgggggcsg cagctgcggc gggaggctgs aggtgggctc 13860 acggccttca caccttgtgc gaasagtggc c sgatcctcc tcagacagca? aacggcggt 13920 cgcagcccca gaagagtgcc gcccctcctg gctcatctgt tccagacacc tgtggtgcag 13980 gcggcctgct cgagggacgg gccagcccca cgctgggctt ccacagaccc caggggaacc 14040 tcgtgaccac ctcctgctag cctgcaggtc tcggtgtggc tgtcaggccc tctgggggtc 14100 agcccaggca cccagccccc ccgtcccaga tcttaaaacc ctgggaggga cacggtgggg 14160 ggtgggggcc ctcccgacac cacctacctt tcgatggtcc cggcgtcctg gtcctgcctc 14220 cccatgcact ggagggcagc cgcataggac agcaggtccg gagtcaagcc ggcatccttc 14280 accacgaata acacatatac cagctccttg aaggcaccct gggagaccaa gccagggtga 14340 gggtctgggg ggatggccca acctccacat cctccctgct ccctggagac cccttctctg 14400 •• tagccaccag ctcagcaggg gacagggtca ccaggcagga gtggccagct gggcagaccg 14460 atgcatcccc ctgaggttct gacacacaag ctccacctgc agaggcagcc gcatggcccg 14520 ccaggtggga ctgtgggagg ttcacgttcc tctgggaggc agcttgttaa acctccagat 14580 ttgtcaattg tgtggatctt ttcaaaggac tgacttggct tgactgttct ctgctgtttc 14640 tgccttccat ttcatcgatt tgttttaatc tttgtaactt cctctcatet acttgcttta 14700 cagcttcttc ggtttagtga ctaaggtgaa ttctagtttc ttcgatctga aggtgacgta 14760 gatgtttcac tttttttccc cccaagatgg agtcttgetc tgttgcccag gctggagtgc 14S20 agtggcacaa tctcagctgg gccgggttct ctgcctccca ggttccagca cttctcctgc 14B80 ctcagcctcc tgagtagctg ggattacagg cacacgccac cacaccagc * aattttttgt 14940 attcttagca gatacggggt ttcaccatgc tggccaggct ggtctcgaac tcctgacatc 15000 gtgatccgcc agcctcagcc tcccaaagtg ctgggatgac aggtgtgcac caccgcgccc 15060 ggccatcacc tttccgaata taggcatttt gtgactataa attaccctgc gagcactgtg 15120 tcagctgcat cccaggactt ctgacaggtg gtgttttcat tttcattacc tccaagtgtt 15180 ttcgaacttc atagtttact tcttctttgg aaattttatt taattatttt tttagataga 15240 gtctccctct gtcgcccagg ctggagtgca gtggcgcaat ctcagctcac tgtcaacctc 15300 cgccccccgg gttcaaccga ttctcctgcc tcagcctccfc gagtagctgg gactacaggc 15360 acatgccacc acacccagcc aattattttg tattcttagt agagacggcg ttccgcoctg 15420 ttggccaggc tggtctccaa ctcctgacct caggggatcc acccgcctcg gcctcccaaa 15480 gtgccgggat tacaggtgtg agccaccacg cccagccatg tatagctcaa atatcccctq 15540 caactttttt ttttttcatt taatttttgg ccaggcacag tggctcatgc ctgtaacccc 15600 agcaccttgg gaggccaaga caggaggatc acaaggtcag gagtttaaga ccagcctggc 15660 caacatagtg aaaccccatc tccactaaaa atacaaaaaa aattagctgg aaaaaaaaaa 15720 gcgtggtggc tcatgcctgt gctccctcca ctaaaaatac aaaaattagc aaaaaaaaaa 15780 tgggcgtggt ggcacatgcc tgtaatctca gcctggggca gctactggga ggagaatcac 15840 ttgaacgcag aaagcggaaa ttgcggtaag ccgggatctc accaccgcac cccagcctgg 15900 gagacagaaa ctttgctgtc gacagacttg gagactctgt cttaaaatat acacacacac 15960 •• acatacatat atatatataa aataacatat atatataatt tttttcttgt actcattttt 16020 cctgacatcc ctgttctgag caatttctcc tttgacccag tggctgctta agagtggcct 16080 gtaaccgtaa cagactattc caaagggaaa aaaaccccct cacacccccc caccccatag 16140 tcctccagct gaagacatgc tgtgacatga ggtggccaca caccagagac cagagacatg 16200 agtcctgggg catttttttt tttttttttt tttgagacgg agtctcgctc tgtcgcccag 16260 agtggctcga gctggagtgc tctcggctca ctgcaagctc tgcctcccag gttcacccca 16320 tcctcctgcc tcagcctccc aagtagctgg gactgcaggc gcccgccacc acacccggct 16380 aattttttgt atatttttag tagagacggg gtttcactgt gttagccagg atggtctcat 16440 ctcctgacct cgtgatccgc ccgcetcagc ctcccaaagt gctgggatta caggcgtgag 16500 ccaccgtgcc cggccggttt tggggcagtt tctaaacaac ctctgtatgg tagaccccac 16560 tagtccttaa tggccacaca attgaaatat tcagttcttc cctttcacca gcttcaagtg 16620 ttcagtagca cacacagctg ttggcagatg cggaaaattc ccaacatcat agaaagttct 16680 actggatggc gctggttaga atacgtggcc gggcgcggtc gctcacgcct gtaatcccag 1Ó740 cacttaggga ggctgaggcg ggcggattac ctgaggtcag gagtttgaga ccagcccggc 16800 caacacggca aaagcccgtc tctactaaaa atacaaaaat tggccgggcg tqqtggtgag 16860 tccctgtaat cccagccact caggaggctg cggcagggag aattatcgaa cccaggaggc 16920 GTGA ggaggctgta? ccgag atcatggcac tgcaccctag cctgggcaac agseagagag 16980 aaaaaaaaaa tctatctcaa aaaaaaaaga tagaagcaat gccttagcct ggctaacatg 17040 ctgaaacecc acctctacta aaaataaaaa ttaaaacaat tatccggggg tggtgscaca 17100 cgcctgtaat cccagctgct cgggaggctg agctcgcagt ccagcgacat ccasgactgc 17160 tggccacccc ggaacgctgg gagaggcagg aggggcccct gctagagcct ctggagagac 17220 ttcgggtctg cagacatctt gattccagac ttctgggctc gtgctaagag tgcgtttctg 17280 ctgtgcaagc cgccaggttt gggacacttt cgtaggggcc gatcccaaaa gcgccctgtt 17340 acagtgtggg ctctctgccc agggaatcca gggggcttgt gaccttggag gggaaaatac 17400 aegacectca tcctcagtcc tcccggagcc tggcgccccc tgcagcaagg aggaaccagg 17460 cagcacgccg cctccacctc gcggtaagag cactgcggac ttcaccgcaa gactggcccc 17520 •• acctgatcct gaatttcgct gtttgatgcg ttaataaaga agcacatcaa gttccctacc 17580 acgaattggt cttaatattg cgatatctgt attttaatat aatagtatcc catgtttacc 17640 caaacattaa gagaagcttt tactgttgtt tctcaaatta gggctgaagg accatggggg 17700 gggagaaagc cgggaacgct tgctgctttg aaagggtgtg taaacaacac cctccaaaac 17760 aaccaagagt tccgaggaga aactttggcc ggatacggtg gctcacgcct gtaaccCcag 17820 ctcctcggga ggctcagggg ggcagatcac gaggtcagga gtttgagacc agcttggcca 17B80 acacggtgaa acccccgtct ctactcaaaa tacaaaaatt aatcgggggt ggtggcgggc 17940 acctgtaact ccagctactt aggaggctga ggcaggataa tcacttgaac ctgggaggtg 18000 tgagccgaga gaggtggcca tcgcaccacc gcactccaac ctagtaacag ggasaqtatg 18060 caaataaata tcccagaaaa aacaaacaaa aagaaaacgg caagggaaat tggaaaatac 18120 ceacaacgaa tccagatgaa gatgggtggg atacatctaa agctgtgctc agagggaatg 181B0 cggcgccagt gaacacccac atttcacaca gaaggatctc agcacagcag cccgaccttc 18240 aaccagaaaa cacctcagga aggagcaaag tcaaccccaa caccaaagcc tcatcccgac 18300 gagggccccg caggctgccc cccgacgagg ccaaaagcac ccctgcccag acagattcac 18360 gagccccgag aaagaacgga aggaaatgct caaggcatta gcagaatttc tccctacttt 16420 tttggccatt ctcaaaattt gagagtcaca cgtgatttgt atttgaaaag cctaaaagaa 18480 ttattaaaat aaaaaacaaa ggacttgaac agagasaaaa ctgggggcta gtecagtcta 18540 aacgagggca agctcctgcc tccaacgacc agggcaggtg gcccggcccc cggctgcact 18600 cacccgccgc gcccagccaa gcatcacggc gttgtacatg tccagcgtga gcagcttccg 18660 cttctgccgc tggccgtggt ggacgaccag caggtggtgg gcgaggggca gctggccagt 18720 gagcaggcag cacttgaaga aggccaggag cctctgctgc tgacctgaga gctgggcctg 18780 cgagtgctgc cccgacgggg cctgctccac atcgaggctc agcttcccag gggcctcctg 18840 cagcagccgg gccagctgct cctcccaggg gctctcgggg gcctggcgcg tgcagtcctc 18900 caggcacccg gccatccgct tgctcaggag ccggggctcc acctgcaggc gcctggtcag 18960 cgccttgaac tccccgctct ggaatggcat ctgcagcttc gccttcaacc getgcatacg 19020 cacccgccgg gcccgcttac ccttctccag tatctttgcc cagcggccac agggcaccgg 19080 •• ggtggcatcc ttggecccca tctggacctt cetgggtggc tggaggctac catctccact 19140 gccacattct gggagccgcg ccacatccac cctgttcacc accacctccg acacgctctc 19200 agcctgcagc tgccgcaccc gcgcctggag cactgtgagg ggcagaaggc gaggacatga 19260 gagggacccc ctccccattc gagcacccgt ctctctggac cctgagccag gccaggaggt 19320 gcaggtggct gagctcgctg ggacccaagg cgtgaattcc tcatacttgc caacaacgtt 19380 gta = ggtctg cccgctgctt tccagacaca cgcaccccac cacctccgca cctccccacc 19440 cgagcctcac agaactcagc agccctaaca agctgccacc gaaacctgca gcaccacgtc 19500 tccccggtca ctggccgctc agaccctcca ggtgcacagg cccagaaccc qgsgtctgtg 19560 acaactccct ccgtccacct ctcagtacct cctctgggct tgcctccaga atctatccag 19620. gtggcccccg cctcccctgc ccctctcact gtctagctca gggcctctgc acagactccc 19680 aggaccctga accgcccact ccctggctca accatggcct gcaagttcgc accccgcctc 19740 agcaagaccc ccccagctgg tggagctgcc acacacacac tcctaggctc ccagtgtcta 19600 cgctgagcca caccggcgga ctagctcgca gggaaaacgc ggctcctgct cgtgccgcct 19860 caggttgcat ttttgccaac caatcaatgc ctaagtgttc tgcatctctt taaagaagcc 19920 ttgttggaaa tctattgctg gccgggcatg gcggctcacg tcggtcatcc cageactttg 19980 ggaggccgag gcaggaagat cacctaaggt caggagttcg agaccagcct ggccaacacg 20040 gtgaaacccc gtctctatta gaaatccaaa aaattagctg ggcgtggtgg catgtgtcta 2Q100 tagtaccagc tacttgggag gctgaggcag gagaattgct tgagcctggg aggcagaggt 20160 tgcagtgact caagatagcg ccattgaact ccagcctggg caacagaaca ataatccatc 20220 agactgttga taaaaaaaaa aataagccgg gtacagggcc gcgcacctgt ggtcccagct 20280 actccggtgg ctgaggtgaa agaatcacct aagcctagga gttcctggct gctgtgagcc 20340 gtgatcaggc caccgtgctg cagcctgaga gacagagcag gaccctgtct caaaaaaaaa 20400 aagggggggg gggacccagg tgtccagatg tggtggctca cgcctgtaat cccageactt 20460 taggaggccg aggcaggcgg atcacgaggt caggagatca agaccatcct ggctaacacg 20520 gtgaaacccc gtccctacta aaaatacgaa aaattaaccg ggcstggtgg tgcgcgcctg 20580 tagttccagc tactcgggag gttgaggcag gagaattgct tgaactcggg aggcggaggc 20640 •• tgcagtgagc caagatcgca ccattgcact ccagcctagc aacagattga gaatccgtct 20700 caagaaaaaa aaaattgctg aaataaaaag acaagcgtga tgtccgcctt cagagtgccc 20760 caaaacccag gagatacttt taggattaac agttgagagc ttcgttttgc tttgttttgt 20820 tctcgagatg gaattcccct cgctgcccag gctagagtgc tctcggctca aatggcatga 20880 ccgcaacctc caccttccgg gtccaagcga ttctcctgtc tcagtctccc cgggttcaag 20940 cgatcctcct gcrtcagccC cccgaqtagc tggcaccgca ggcgctcacc accatgccca 21000 gctaattttt gtatttttag tagagacagt stttcaccat gttggccagg ctggtcttga 21060 actcatqacc tcttgatccg cccgccccgg cctcccaaag tgctgggatt acaggcgtga 21120 gccaccgcac cagscctcgg acccttgacc tcttgatccg cccaccttgg ccacccaaaa 21180 gtgctgggag tacaggcgtg agccaccgca ccaggcctcg aacccccgac ctctcgatcc 21240 gcccacctcg gccacccaaa agtgctggga ttacaggcgt gagccaccgc acctggccag 21300 gtttcttccc tttataaagg ttctcccgcc tctcccttcc cggctgccta atggacgcag 21360 acaggatgtg ggacagaagc accggcggga agcaagcaca gggaagctcc cacctccctc 21420 ccacaccacc agccagqcca qgacgagggc ctgccaccgc tggagcctgg gctgtccctc 21490 cagtcatcca ccaagtttcg gtctccatta ggcgcctacc ccccagagcc aagccaggac 21540 agccgagrca gttcagggtt cacatcctgg ctctgcacat gtggccttrc ccgeggggcc 21600 gggggggggg tctctccaga cataatcttg ggcctcacct atgtccctgg aaagtgggag 21660 cacctggtgg ggttctgggg agggggaatt acgagagctc caggaagcag cctgctcagc 21720 aaggaceggg cccatgagcg gtgcaagaga tgtttcagca acgccgtctg ggcgtgtcct 21780 gggacccgag aggtggagac cgccctcagc ctgtctcaga atctgagccc ttgcecctcc 21840 tcccgscagc agggagcgga ctctcctctc ccgggccgcc gtgggggtcg cgctcaccct 21900 ccagcagctc cacgtggccc cagtccttcc tgcggtcttg gtcttgctcc tgggggctgg 21960 cggacgagct cctcctgggg ccgcagacgc caccggcggt ccctgcggga aagacgagag 22020 cggctgagcg gggccgggcg tgtgggcggg ggcctccata aaggcagaag ccgaagggcc 22080 ggagccctaa gaagggcaaa acgcagcgga aactctcgga gcacgggctc aagctggaaa 22140 gaaactaaga cagcgaaggt ggaagggccc cgccgcggcg aacacgggog cggaaccgcc 22200 gagagagggt tcctcgcact cgaggtgcag caggtcaaag gttaagagcc ctaaacacca 22260 cacctggggt caggaggctg cataagaaac cacgagtcaa aggtcagacc gcacggagga 22320 gcctcastcg aaaagcqqgc aagggcgagt ggaaagcggg gccgggtcgg tgggctgcgc 22380 acgcccaggt gcaaagaggc aaaggtcaaa gcgccaaagg gcggggagga ccccggccco 22440 gcccacgccg tggcccccgg gctgcctggc cgtctccctt tgtgttacct tctttgccgg 22500 ggagtcccgg gcggccqcaa gqccgtaggg ctcgttcgag ccccgcccoc ccgcggcccc 22560 agcaaagtgc .cgacattacg cacgccgctc caggccacec caccggcccg cgcctgcgca 22620 cgcgcccgcg ccgcctgccg ggagttgtgg tttcatggtc gacggaggct gcqaagggaa 22680 accccagccg gaagtagact cccaggatgc agcggaggcg cgaaggcacg cgccggtgga 22740 cgctctgatt ggctcctcct gctgttttta aagggagggg gcggcaca to gctgttgecq 22800 tggcaactgg gaqgcactct caggctgttt tcccgaggac ctcaaatccg gacttttttt 22860 ctgttcctct ttcttttttg gttttgtttt ggacgcgttg tggcccag c tggagtgcag 22920 tggcgtgatc atagctcagt gcagcttcga actgctgggg taaagagate ctcgcccctc 22980 agcgctggga ggcttcccaa ttgcagacgc cgccaccgtg cccggccccc tctttttttt 23040 tactcatcta tttcaaggea ataacgagga cagcatctgc aatttaga ^ a ttcctgtccg 23100 caaccttcat tgctccaacg acaacctctg ggtaagagcc attaggatcc cgtctatcat 23160 ggaggaagct gaggctcaga gagggccacc aagttgctgg aagacaca c acgtgcgacc 232 C tcagggaggc gaaagcccca tgcaaggaga gtccgcgaga ctcccagcet ccagc ttcag 23260 tttaccctcc aatccccaag ccctcagggg caggagccga atggagcggc aggcttggat 23340 agtggggtga tcacctgcta ggtcaaggga atgaaataaa cctcggagcc tagagcctgc 23400 cctggtctcc gcgtgatcct gcctaggagg agcagggcgg gagctttaga atggaacctg 23460 gaaggtgtgc ccacctgtgt cgttcagccg gggcagcagg ccagaggcgg gagcgcctgc 23520 tgtggggcag taggcttggg aagggtgaga ataggaatat ctgtgttcca ctgggggcaa 23580 ggctaatatc ccagttgcaa aggggagctg gtttsgtggc tcaggcctgt catcccagca 23640 ctttgggagg ctgaggcggg cggatcacct aaggtcagag ttcgagacca gcttggcaaa 23700 tacgcaagca tgcctggcaa catggcaaaa ccccgtctct agtaaaaata caaaaactat 23760 •• ccgggggtgg tggcgggcac ccgtaatccc agctactcgg gaggctgagg caggagaatc 23820 gcttgaaccc gggaggcgga ggttgcagtg agccaagatc tcgccactgc actccagcct 23880 gggtgacaga gcgagaacct gtctcaaaaa aaaaaaagtg caaagggacg ccagttcagt 23940 gcctcaggcc tgtaatccca gcactttggg aggctgcggc gggaggatcg cttgagccca 24000 ggagttccag acaagccttg ggcaaccgag atactgagac ccaaaggaaa ccagtctcca 24060 aaaagaaatt agccaggcat ggtggtgcac acctgtggtc ccagatactc gggaggctga 24120 ggcaggagga ctgcttgagc ccaggaggtt tagactgcag tgagccgaga tggcgccact 24180 gtactccagc etgggttgac agaacaggac cctgtctcaa aacaaaacaa gtgcaaaggc 24240 cctgaggcag gaacaagcgt ggacagagga gcaatttgag cagagtgggg ctggggasaa 24300 ggagcaaaga tgtagctggg gctcagttag ggggcctgac cacacggggg rtcgggggcc 24360 tcagctcaaq ctatcctcca tccccaaacc ctggcacttc agtttcccca tcagcccaga 24420 acgaggactc gacctcactc tggaagggcc tggcagcctc cttacagcac attccagacg 24480 ccgctgccga cgcctgcgtg agcgcactga tgccaccggc tgggaacgct ctcgacagac 24540 ggcagcaccc tccctcacct gcctcagtcc acctcagggt gccecdgcgg gctgtgacct 24600 cagacctcac ccactactgg ggtcacctgc ctggccctga atcagccagq cctggtgtgc 24660 caagacccac agacaccccc tgcacccctg caggctggca gagccaca = a cttgggtgga 24720 aaocgacttc tgaactattt caccatccct tacgcgttag cccctccttc catccgatga 24780 gatcccagca ctttgggagg ccgaggcggg cggatcacgt gaggtcacjra gtttgagacc 24840 acatggtgaa agcctggcca accccgtctc tactaaaaat acgaaaatca gccgggcatg 24900 gtggcctgtg cctgtaatcc cagctactca ggaggccaag ggaggaaaat cacttgaacc 24960 tgagaggtgg aggttacagt gagccaagat cgcaccactg cactccagcc ttgggcaatg 25020 tagccaaacc ccatcactac aaataataca aaaaaatttt gttggctgtg atggtgcctg 25080 cctgcggccc catctacttg ggaggctgag gtgggaagat gtagaattcc ttgagccagg 25140 aggcagaggc tgcagcgagc tgtgactgag ccactgcact ccagcctccg cgacagagcg 25200 agaccccgcc tcaaaaaaaa aagaacataa tctgggtttt or agcagtttct ggaataag = 25260 gaaacag tc attgcccaaa ttccagcctc gcaactctgt agccgccacc accccccagc 25320 •• cccaccattt attttaacta catctgtctc caccactcct gtattaagca aacgcaatat 25380 tggtggctca tggccggtca tgcctgtaat tccagcactt tgggaggctg aggcaggcag 25440 atcccctgag gtcaggagtt cgagactggc etggccaacg tggtgaaeoo ctgtctccac 25500 taaaaattca aaaattagcc ggacgtggta gtgggtggtg cctgtaatcc cagctacttg 25560 ggaggctgag gtaagagaaa tgcttgaatc caagagactg aggttgca c gagctgagat 25620 ctcgccgctg cactccagcc tgaacgacag agcgagactc cgtctcaa to ataaattaat 25680 ttaattattt aaatacaaca ttcttgctta agttttacga agagactcsa tatcaccatc 25740 saaagtggga aaccatacat ctggecgggc gtggtggctc ccgcctgtca tcccagcact 25800 acqggaggcc gaggcgggcg gatcccctga ggccgggagc tggagaccag ectggctaac 25860 atqgtgaaac cctcatctcc aataaaaata acaaaaatca gccgggcatg gtgggtgcct 25920 ctattcagga gtaatcccag ggctgaggca gaagaatcac ttgaacccgg gaggcggagg 25980 ttgcagggag ccgagatcac accactgccc tccggcctgg gcgacagagc gagactctgt 26040 aacaaaacaa ctaaaaacaa aacccaacca agcaaacccc acagagtcga gaatcgctag 26100 atggaagggg atggcccagg tccctggagc ccctgtgaca aattaccaca aactcggtgc 26160 cttaaagcaa cgttcatttt cttacatttc tggaaatgaa aagtccaasa tcaggactgc 26220 ggggccgaag tcaaggtgtg tggaggcctc gctccctcca gaggccctcg ggctccttcc 26280 tgcctctccc agcttttgaa ggctccaggt gtgcttggcc tgcggccaea tcdctcccgt 26340 ctcggcctct gtggtcgcac tgcagcctcc tcgtctgcct gtgtgaaacc tcctcctgtc 26400 tccgtattgt gaccgcgttt aggatgcccc aggacaatct tctccatacc gttcagatct 26460 tcatggtgtc aatatattga gactcttctt ccaaataagg caaatgtcac attctaggga 26520 tcagggtggg gacttacctt tgggccaacc acagaggcta caaagaggaa gacaccactc 26580 aatacaaagc gtgcgccagc ccagccctga tcggtgtttg ttgttgttgt ttttgtttga 26640 gacagagtct cgctctgtcg cccaggctgg agggcagtgg gctcattgca catgatctca 26700 acctccgcct cctgggctgt atagattctc ctgcctcagc gctgggatta ctcctgagta 26760 caggcg-gaa aaggagcaag gctctgcccc agccacagcg cggatgcacc ttgaggacgt 26820 catgctcagt gaaagacgcc agacacagaa ggacacacag tgcgtgatcc cctttatatg 26880 •• aaatgtccac aacaggccca tccacagagg caggaagggg atgtgtgggt gccgggggct 26940 ggcagagggg atgagtgaca gctgatgggg cttcttcttg cggtgatgga atctcctgga 27000 actagacagt cgtggtggtt gcacaactcc acgaggtact aaaatcactc aactggctgg 27060 gtgcagtggc ccatgcctgt aatcccagca ctttgggagg cagaagcagg- tagatcacga 27120 ggtcaggsgt ttgagaccag cctggccaac atggtaaaac tctgtctcta ctaaaaatac 27180 aaaaactagc tgggtgtggc ggcaggtgcc tgtaatccca gctactcagg aggctgaggc 27240 aggagaatcg cttgaaccag ggaggcagag tttgcagtga gccgagatcg caccactgca 27300 ctccagcctg ggtcacagag ccagactccg tctcaaagaa aataaaatca acaataataa 27360 ctgaactgta cagtgtaagt gggtgaattg tgtggtatat gagtgatgtt tccgaggtgt 27420 cattaaagaa actcagacgc ctggggtggg gccagtctca cegctgtgcg tcccatcccc 27480 atcatttctc acaaggccct cagatcaccc ttccgcggtg gggggcggac actctaagaa 27540 gggsagacct gggctcctgc tggcgagaag gcggtggaca ttccctcagt gtctggtgcc 27600 gcgccccctg cccagcgtgc tccgtggagg gtctcattgt cttcctccag acgtctcttt 27660 actggcccat tttacagagg cgqaaccgaa gcttggggtg ttggccacag ggctctagtg 27720 tgcgaagcca ggccaggctq qacctcagcc atggggaccc gactgtggca ctgtccctca 27780 cccgccacac cctctgCgtg acccgcctaa gccaggaaga gagggccagg agatgcctga 27840 aggcatccca gccaccaaga gcgtccagcc agaccggtta tccetccaca gggctccccg 279C0 gcaggacagg ctggtcgcca tgtcttcagc ctggtgctat ttaaaggtgg gtgccacctg 27S60 gggctgtggc cgcagggcca ggactgggct gctgggagct gtgtccccac agcggaggtc 28020 gccgcccctc tcaggcctcg gtttccccag ttgtcaatgc ctccacttgg ctgcgagtct 28080 gtgagggtca ctgtgctcac cttttggggc ccagcgcatg gggcaggcag aggaagggtg 28140 ggggccagcc gccttgctgg gtggttcccc gtggggcctg gggtatggcc ctaagggagg 28200 agcaagtgtg ggtgcgaatg gggccgcccc attcctgccg cctccgacgt gccccgccag 28260 ccggccaccg acaggtctac gtggctatcc tccctcctgc ccacctacct gcccaaacac 28320 acgtccccag tcgtcacctg cccacccacc cgcgcattcc caeacccttg tgggcctggc 26380 tttcgggaaa ccacaacttg agtcccacga cggggagaga gggcatgccc cggagcctgg 28440 ggctgacgca ctggtcccac cgcggcagga cctcccgtgt ccatctctgt ccccaagcat 28500 ccccgcetcp gcccctctct gtctctgtgt ctctctcgtc tctcscggtc atcttcettg 2B560 tgtctettga ctgccgccgt ctttctgtct ctgtctccct ccgggtctcc gtctccctcc 28620 aggtccctgc ggcccgcgtc tcacactccc gcccccgcaa cccgaggtcc tagcccgccc 28680 gac sgggsctcsg ctgactcocg acgcccc gcgagacaaa caacaaacgc gcggaggccg 29740 agcgcggsqt cccgcacggc cgcgcccctg tgcacctggc ccccgccccc gagacgtccc 28800 attggccggc gccctagcct ggtcccgecc aagtggaccc cgcccccgcc ccqaqgcacc 28860 ccattggccg gcgtccccgc cccagcgaac ccggccccgc ccccgaggcg ccccattggc 28920 cccgccgcgc gaaggcagag ccgcggacgc ccgggagcga cgagcgc? ca gcgaaccggg 28980 tgccgggtca tgcgccgccg cctgtggctg ggcctggcct ggctgccgct ggcgcgggcg 29040 ccggacgccg cgggaacccc gagcgcgtcg cggggaccgc gcagctaccc gcacctggag 29100 ggcgacgtgc gccggcggcg cctcttctcc tccactcact tcttcctgcc cgcggatccc 29160 ggcggccgcg tgcagggcac ccgctggcgc cacggccagg acagtgagcg cggggcggcg 29220 ggggcctggg gtggggaggc ggcgggtgac ggcaacgcgg ccgccgtctt cacggtgacc 29280 tgcgcccgcg ggggagtccc ggaggctcct ctgtgcagcc teqqccccag tttccgtggt 29340 ggtgca ctgtgágatg? cct gcctggtggg agggttgcac tgttaaagcg aaqgczgcaq 29400 cggcSQaccc ggctcagggg cagaga ^ GCG tccgtgtggt acaaccctgt gggrggggcc 29460 acccatctgc aggtgggaaa ctgaggctcc agaggggctg gggcaggccc agctgcatgg 29520 cggaagcggc g gggggctga cctccg ^ act cctgacatca cagaatcCag tcagggctsc 29580 ctgagtcggg gccccctctg cttcttccca gacaccccat ctggcaggtg aggacaagga 29640 agggatggga ggcacacaga cctgcccagg gtcacactga caggggtggc ggagctgggt 29700 ccecaQaggg cccaggacgt cacggagcgg gcgtctctgt ccccagggtc tgccgagcac 29760 ac ^ ag gccctcagtg tttgtggaat gtcaggagca agaggagagg ctgggcacag 29820 c ggg? jatgt gggtacctgg aggccagggg agtcggtgtc cccgccgggc ggggggcact 29880 gggaa ^ gggq cccgggcccg ctggctgccg cctgaatcac caccat? agg gcaggtaatc 29940 •• ccccttg c cttcccaccg ctttcatctg ggcgccaagg ccctcattag gccgcacgtg 30000 acgag ^ gcgg acaggggact ggctgggccg gtccatccat ggcggg < ¿Atg gccaggcggg 30060 q QQC? Caqq qccqqqqc? Q sqq ce ^ GCT ccgctgcctg acctgg ^ 3ca gtctctgcct 30120 ctctc? AAGC cccggtttcc ccagctggac ggtgatgggg gtgagggcta gctgagggct 30180 cccctijccct tcgtgcattc gctggtcact aatcgggcac cttgtgggCg ctgtgctccg 3Q240 cargg? Fggac ccagtggtga cagagaCgcc caccctcctg gggctCQcag agcagaggcg 30300 cgcagtagtt agacacgtga acaagggcgc ggtgggtgc acagaatagt gaacggttgg 30360 ccgggtgcag tggctcacgt cggtaatccc agcaetttgg gaggcc ^ agg cgggcagatc 30420 acgaggtcag gagatcgaga ccatccCggc taaca ggtg aaaccccgtc tctaccaaaa 3048O atacaaaaat tagccgggtg tggtggcggg cgcctgcagt cccagctact cggsaggctg 30540 atgacgtgaa aggcaggaga gccgggaggt ggagcttgca gtgagctgag atcgcgccac 30600 tpccctccac cctgggcgac agagcgagac tccgtctcaa aa aaa ^ aa aaaaaaagae 30660 cagtgaatga cgtgaacaag ggtgc ^ ggtg ggtgcgcaga acagtgaacg gcgqtgttgg 30720 caggcacctt gccaggggag gggagcjtgca gggcgaggaa ggggccdggg gagatcgtga 30780 cacagacgcc ccagaacaac cacct? _aaag acgttcctgt stgtcctgqa aggtcgggct 30840 gggaggCtgc cccgaggagc tt tcattttg acagggagct ggccgqgcac gcagggaact 30900 gtacacccag ctgacaaagc ggcagacacc caggccgggg tgagcgastg tgggtgagga 3C960 gtggcggctg gccccagggt ccttgcegga caagacactí cagctcaggg tggsacasgs J1C2Ú ctcacccagg gctacccaca gacgatggcg tccaaatctg gctctgccac tcccaggccc 31060 caactggccc ctctgcaacg tgggctgctg agcgggcttg gtaggacagc tggcatacag 31140 tcggcqctca agcatgtctg tggtgtccca taaaccaccg gtgtcccact ctaggccact 31200 gccagcccgg cctccagtcc agagtccoag tccggagtcc cagtgactgt gcgtgggccg 31260 ggcagctgag ctgtgagggc cgggctgggg gctceatatg gggtggtgtg agctgtgagg 31320 gccgggctgg gggctccatß cggggtggtg tgag tgtga gggccgggct gggggctcca 31380 tatgcggtgg cgtgagctgt gagggccggg ctgggggctc catatggggt ggtgtgagct 314 i0 gtgagggccg ggctgggggg tccctggggt ggtgtgagct gtgagcgccg ggctgggggg 31500 tctctggggt ggtgtgagct gtgagggccg ggctgggggc tccatatggg gtggtgtgag 31560 •• ctgtgagggc cgggctgggg gctccatetg gggtggtgtg agctgtgagg gccgggctgg 31620 qgg tccctg gggtggtgtg agctgtgagg gccgggctgg ggqctccctg gggtggtgtg 316B0 agctctgagg gccgggctgg ggggtctctg gggtggtgtg agctgtgagg gc? Gggctgg 31740 gggctccata tggggtggtg tgagctctga gggccgggct gggggccccc tggggtgctg 31S00 ctggtcgctg gcZcaXtgac agttatcagt ggtctgggtg ggecctgccc cttctgactc 31860 ccacatccca ggaacccttt cccaaccttc ctcgtggtgt tgctg-CECC 31920 czqacgtccg tccctctggg tgtgtgggag cccccccgcc atacacacac acagatgctg ctcttgggct 31980 gagctgcagg gacagcgctg acetggccct cccacggggt cctca CGAT ctctgcactc 32040 ccccagctcg tgggggccgt cctgcttccc gttccctccg ccrgctcctt gctcctccec 32100 cacatgctgg ggggggctcc tggtqrcagt cacggetctg ggggstcctg agtgtccgtc 32160 gt gtcggga ggggactcgt g? tcccgggg gtctcctggt atctgtcgtg gtcctgaggg 32220 ccccgcacga agcacagcgg acagcagcgg tgctgggggt ga ccsgcaa ggccctcccc 32280 gscccccgcc tcccccaggc atcctggaga tccgctctgt acacicgggc gtegtggtca 32340 ccsaagcagt gtcctcaggc ttctacgtgg ccatgaaccg ccggigccgc ctctacgggt 32400 cggtgagtgc cgggcagggc tgggcggcgc gggcagggtg gggarggtgg gccggcctca 32460 cccccgcccg cagcgactct acaccgtgga ctgcaggttc cgggagcges. tcgaagagaa 32S21 cggccacaac acctacgcct cacagcgctg gcgccgccgc ggccagcciH tgtccctggc 325SC gctggacagg aggggggggc cccggccagg cggccggacg cggcggtacc accegtecgc 32640 ccacttcccg cccgtcctgg tctcctgagg ccctgagagg ccggcggctc cccaaggtgc 32700 ctgggctggt ggcgaggggc ccggccacgc ttgtecttcc ccctgcgggc tccgtaagcg 32760 ctgagtgccc accgtgtgcg ggcgctgtgg acacagccca ggagccctcc aggggggtcc 32820 cagcctgagg gggtggtgqc caccaagcag gttcaatcct gagttgggga cctcgaggac 32880 ccaacagggc gcctctcggg ctgaaggacg cagacgtcga aaggtcgagg gggacgtccc 32940 aggcaggccc cggcagaggc aggggctcgg ggtggggagc acgttggsag tgggggcagg 33000 agcggagggg aggggagggg gccggggags cggtgacaga cgccgcagaa caccagcctc 33060 gaagccggtc ccgtcccggg aatctgcaaa tacaacgcet tgcgagc = ca aaggcacctg 33120 •• caggtgggac ggagatggag gagcatccag ggtggggggt ccagggcccc agtgtcctca 33180 caggctcctc acgacaggag gcgggacagt gagagccaga gagagatggg gatgggccgc 33240 gctgtggccg tgaaggggag gaagggccot aagctgaggg acgtgggtgc ctecagatgc 33300 tggggaaggc gggaacggtt ccgcactgga gcccccggga gggaccggcc tgctcctgcc 33360 ttgatatgag cccagtgg to cccagtttgg actctggcct ccagaaccgc cagaaaataa 33420 acgtagtaag ccatcaactt tgtggtcttt tgttacagca GACGTC gaa acatgcacac 33480 actgttctca ggtstctgaa tgacaaaata agcctcagat cccccggggs agggcggagg 33540 ccaacgcctc ggtgttcctc cgatcccccg ggaagggcgg aggccgacgc ctcggtgttc 33600 ctcggatccc ccgggasggg cagaggccga cgcctcggtg ctccr sgat cccccgggaa 33660 gggcagaggc tgagggcag? agccgtgctg ggtgcasggc aggcicgggg gcttcatgcc 33720 gctgtcctgc gggacgcaga gagggctggc cgtcggtgtg ggggc cccc cacctgtgcc 33780 cagcgccctc ctgacatcct gactccgctg ggaetcctgc ctacagccct gggagtcaaa 33840 etccagcetc tcagagaaaa ggtcagagcc aagagcccca cagcotggag ccaggcagtg 33900 acaccctggg cctgtctccc cttctgtgtg tggggcgaca gcagcatcgc cctggtgaag 33960 tcoccgggga cggccagggc tccatcccca gccgccgcct TCCs ataas tacaggaaga 34020 ctgggccgag gcacttgctg ggaggtgctg agcagcctga cacggaaaac ccttctggga 34060 agggagggte qrcgcccggcc cgagagcttc tgctcaccct gcagacae = a gcgagcccca 3414C ccccagggga caccaggcgg cctctgggga catctttggc tggcatgcrag tgggtggagg 34200 acagggctgc acscaggatg tccccaggtt ggcagtgtga ggggagatcg gcccacgttg 34260 gccagtcgga gg cgtcgcc ßettgagttg tcactgggag ctgcacaggt caccacagct 34320 gaaataaaac ttgctggcac cccacgcagg aacgtaacat gtgcctcgaa gaaacgggtc 34380 agcaggccgg gcgcgggggc tcacgcctgt catcccagca ctttgggagg ccgaggcggg 34440 ggtcaggaga tggatcacga tcaaggccat cttggtcaac atggtgaaac cccgtgtcta 3450 0 ctaaaaatac aaaaaattag ccgggcgtgg tggcgggcgc ctgtascccc agctactcga 34560 gaggccgagg cggggaatcg cttgaatccg ggaggcggag gttgca? Tga gctgagatcg 34620 cgccactgca ctccagcccg ggcgacagag cgagactccg tctcaaaaaa aaaaaaaaaa 34680 •• aagaaacagg tcagcagttg tttctttgtt tctaaaacag agcgtggaat gggcgtacag 34740 crccgcacat cccagggcag tgaaatcccg gttcacacag agcccccagc agcttattcg 34800 caagcccaaa cctggggacc cccgttgtcc tcaggcagtg aggtgg_? GGC cccccaacag 34860 agaasagcgg cctgggggca cagaaccagc ggctccccag gcagtgaaaa gaaatcgcca 34920 t? aa aacc ccaaactgtt gcaaactgtg cttccgctta cgaagcactc ctgagcggca 34980 gggcggatgg ggagagggc? gctgcaggcg cgaggggcc gggg ^ c ^ cag ggg gcgggc 35040 ctceccagga CCCT tcctg tcgtgcagca ggctcctggg gcaggcaaga caccaggggc 35100 ggccacctct tactgctgtc tgacctcgag caatgcggcc tcacagcccc caccagggtg 35160 ccggcgtcct ccgggcccag cgcccccgag gctcatgcct gggtgsggcg aaccaatcgg 35220 tcctgctcct ctggccactc cacgcgaggg aagtcccagc ctcacaggca ggcgcacacc 352B0 ccggcagc3t ctctgacaaa ggccctccag TTCC ^ agttt cag? tcccg ccgctgcaag 36340 cctcacctgc ecagccctcc tctccagctc caactccaac tccciagaac cacacggac 35400 acaeagaacc cgagccttgt ctccctcaac gcctcctgac ccaee.actcc accttccaac 35460 aggaaaacgg ctcggccggg ggactgtgac ccggascagg cggticagcc tgtcgcgcag 35520 aeteggggcc taaaacactt gttctctcag tccggagatc aaggicqatc cgaggtaacc 35580 tccccacctc gstgtcctcc atgcaacctc gtcttaggge accgggcacg ttacctcgtg 35640 aggagccgag tccgcgggtc ctggggttga gacgcggacg ccctcagggc tggcactctg 35700 ccctggcggc cacagtcatg gaagtcccaa cgcttctctc ggctccgcaa ccccagaogg 35760 cggccacgag gagggcccgc cacgcacgac cccagagggc ggccaccagg agggcccgcc 35820 ac gcgcgacc ccagagggcg gccaccagga gggcccgcca cggcgttgcg gcagcagccc 35880 agaaggtgcc ctgcgcacgg tccggacagg tgggatccga gttacctggc caagggggct 35940 cgtcgcggga gacgcagaca eacagtgaag agtgtggtgc agagcggagg gcgggagtct 36000 ttggagaaca ggtaggggcg tggggcacgc gcctcccacg cgcaggagcc gtctaccgtg 36060 gagycacacs ggtggtcctg ctggaggctc ctctccgtta gctgtcccca tcgtctgatt 36120 cttggatccc aggatggtgg gatcatcagc aactgagatg aacccactgc cccggccccc 36180 tgagcccgca ggtccccacg ccttgccagc tgtgccegag ctggctgcac cccgggccag 36240 •• accttgagca gcatccagca gtggggtccg gcttttcaga aggggccagg aacccgcgtg 36300 gctgaggcgt gaccgaagcg zqggqcaqsq gcgctgggcc ctggcgcttt aacgctggcg 36360 tttctggttt taaattecac gacccagtga cactgccacc ctgctacctc gccagcagcc 36420 ctcctgggct taacttcggg agagcagttt tgctagccgg ccctgggtgc caagccctgc 36480 gacccctgga agsaggcgca gacaggaccg gactctgcag agcccgacca gcctcccagc 36540 ttggcctttt cctgacgcac gggcgcagaa ggaaagccac agcaccggcc tctctttgts 36600 agcagtgtat tttaaatagc cttcaagata cacatatttt ttccttcaaa aaagtctgtc 36660 ggagcagttt tgttcttgaa tttcgctggt catcctcatg gtcccgagoc cccctact 36720 cc ggatcgtgga ggcggccgag ggggaggctg ggggcccacg tggcccgtcc tggcggcacc 36780 tacagcactg ggggagccgc tgaaccccgt gcttcagcqc tgggggagcc gctgggcccc 36840 gtcctccgcc acaaaccaeg carggccgcc. acgtgagctc aaacgtccgt ttatttcaaa 36900 tttaaaatta gcagraataa taaa atctt tccaccgctg aacttttaga gggtgaggtt 36960 agacagagga cggggaggct ggggacgccc cagaggggac cat ^ tggccc acgccttccc 37020 eacccagggg qccggtgggc cgggcccggg tcctgccctg qaacsgcegg gacctgcagc 37080 gctgaccagc caagcgtggc gccgccgggg cacccagtct gtcigtgccg tgtggcgctg 37140 gctgagggc g ggcgggaaag gccccgtgct ttcccgac? g ccgacgt? gg ct cjcgagr t 37200 gcttgtggcg ttctcgttgc tgggegagct ggaggaggac gatgac ao; acgaggagaa 3726C gcccacccca gtgaggccag gggggttcgt ggccgtgt tc tgtcccgt ga 37320 ggctttttcg gcagacgggg cagctgtcgt gctttgtggg gacagaggca gggacgggag aaggggcaqg 37380 ttagaggcgg gagggccgcg gtcggggtgg gggggcgggt gggcggggta ctcaccCgcC 37440 ccagccaggg cacgatgcag ccgtcgtgga acaggtggtt gcagggcagc tgccgcacac 3750Q gctcacccag cgcgtagtcg tccttgc? ca 37560 cagggcactc gagcccggag ectgcgqgag rgtgcagctg cggtcacagc gggcgtg§gg ggcctgccga gccttcaagg gcaggctact 37620 ccacagcccc agccggaggc cgcccct ^ ag cccagcgagg ggagaaaa gc cgtgtgtgtg 37680 tcccccgggc tgccagaggg gacctggaca gaaccctctc ctcccasccc accttcaggg 37740 aaacgctcga ggccgggtgc ggtggctcac gcctgtcatc ccagcacttt gggaggCcga 37800 •• ggcaggagga tcacctgagg tcaggagttc gagacctgcc t gaccaecat ggcgaaaccc 37860 gaaaatacaa cgcctctact gtatgagtca ggcgtggcgg cgggtgcctg taattcccac 37920 tactcgggag gctgagctct catacctacg tgctcctcag tgacggggac ggtggggagg 37980 gcctggattt tctctttatc tgccggtggg gggcctgtgt tttcaaactg attgaggagc 38040 tgaaagacaa gaggcgagag tgccgggagc tcctcggggg Qccggcccgg gsct ccgaaa 38100 cgcgaggctg caggacctgc aaaagcaCCg aggccgcgtc tt cet gsgc cctg.jgcccc 38160 ttggagcccg cccggggtcg gagatc 3S 186 < 213 > Unknown < 220 > < 223 > Description of the Unknown Body: Unknown < 400 > 39 cgccggcgct tgacctgact ttcatgaatc gaaaaggaaa TCCT ct ATGA acgcactgca 60 tcgcaccggc gccggaacgc tactgqccgt gttgctcgct tttsgtctga ccggct GCGG 120 ggagaaggag gaggt ccagc agtcgctcga gccggtggct TTTC = - = STAP ctgacgagt g 180 tcaegtgtgc ggcatgatca tcactgaett ccccggcccc aagggcca g cgqzcgaaaa 2iO gcggggagtg aagaaattet gttccaccgc cgaaatgctt gcttggtcjc tgcasccags 330 aa ctcgatgcca ccgtctg agctctacgt ccacgacatg gggcgcagtg tttgggaaaa 360 gccggacgac ggCcatctga tcgacgcaac cagcgcctac tatgtsgtcg gtacgtcact 420 caaaggcgcc atgggcgcgt cgcttgcaag ctttgccgag gagcaggacg ccaaggcgct 480 tgccggcatg cacggcggtc gtgtgctgcg cttcgaggaa atcgatcagg cgctgctgca 540 ggaggctgca agcatgcagc acggcggcat gcacgaccat gcgccaaacg gtgcacataa 600 ggccactgag cgcacacgca cagcagtggt ctgaacagca cacacaagaa atcgaggtaa 660 gcacaatgat gggtatcagc gtctggcaac tcccgatcae tcttcecatc gtcgtcatgc 720 < 21Q > 40 < 211 > 127 •• < 212 > DNA < 213 > Unknown < 220 > < 223 > Description of the Unknown Body: Unknown < 220 > < 221 > IT IS NOT INSURANCE < 222 | 9) < 223 > It can be any nucleic acid • C22D < 221 > IT IS NOT SECURE 222 > [101) < 223 > It can be any nucleic acid 220 > IT IS SAFE to be any nucleic acid gcggccgcnc ggcgctggct gctgtgcg to ggccocggcg ggccgcgaac cgccccgtcc 60 tcgccctcct gccctgggtg cggccccccg ggtcccggcg ricccac cgc cccggc? Tnc 120 ccgcgct 127 < 210 > 41 < 211 > 6856 < 212 > DNA < 21 > Unknown < 220 > < 223 > Description of the Unknown Body: Unknown < 400 > 41 actcgccaag tgatcgaccg gcccctgagg gccgcgacgc agagggcgcc ccgtgcactg 60 gcacaggcgg ccttgtgcgt tagactctga tattcgtgcg ccctctcgtt ggcaggacca 120 tccatcctgt gtgccggggg ccgcgcacac cgatcccgga tccgcctcgg ccccgccctg 180 cgcgcccctc cgttctcgac ctcccegacg ctgtctgaac acgcgtcgcc gggggacgac 240 ggcgggcggc ccgcctcggg ggaggggtaa gcgtcccggg atgcccgttc aaccgttccg 300 caaggctcgc ccatcgtggg ggagaaccgg cgcgacgcta ggagagacaa gtqatccagc 360 aggagtcgcg gctcaaggtc gccqacaaca ccggtgcgaa ggaaatcctg accacccgtg 420 cgcccggcgg ttccggacgc cgctacgcag gcatcggcga caccatcgcc gccaccgtga 480 aggacgccat ccccggcggc aacgtcaaga aggcgcacgt cgtcaaggcc gtggtggtce 540 gcacccgcaa gcagccccgc cgtcccgacg gctcgtacat caagttcgac gagaacgcgg 600 cggtcatcct gaagaccgac ggcgagcccc gtggcacgcg catcttcggc cccgcgggtc 660 gcgagctgcg tgacaagaeg ttcatgaaga tcgtgtcgct cgccccggag gtgatctgac 720 ctcatqgcca agatcaagaa ggacgacctc gtgcaggtca tcagtggcaa ggacaagggc 780 aascsggqca aggtcctgcq egtgCtcceg acggatgagc gcgtgctcgt cgagggcgtg 840 aaccscgtga ccaag ^ a cct gcgcgccggc caggacaaca acggttccac cgagggcggc 900 ctgragqtcg tcgaggcccc gatccacatc tcgaacgtgg ccgcggtcga cccggagacc S "60 aagaagccga cccctgtggq ctaccgcttc gagaccgtcg agaaggacgq cgtgacgaag 1020 acgceaagg tccgcttcgc caaggcct q gcgaaggagc tctgatgacc gaggtgcagc 1080 agaecgagaa ggtcaccccg cgtctgadga ccaagtaccg cgaggagatc cgcggacgcc 1140 Lgcaggagca gt ccaglac gggaacgt ca tgcaggtgcc gggcctcgtg aaggtcgtcg 1200 tcaacatggg cgtcggrgas gr.cgccaagg actccaagat catcgaccac gccgccaccg 1260 acctcaccgc catcaccgcc cagaagccga tgatcaccaa ggcccgcaag tccatcgcgc 1320 agttcaaget- gegtgagggc atgcccatcq gcacgcacgc caccctccgt ggcgatcgea 1380 tgtgggagct cctggaccgc ctgg cacgc Cgccgccgcc gcgcatcogc gacttccgcg 1440 gcctgtccga ccgccagttc gacggcaacg gcaactacac cCCcggcccg tccgagcaga 1500 ccgtgttcca cgagatcgat caggacaaga tcgaccgcgt gcgcggcatg gacatcaccg 1560 tggtgacgac cgccaagaac gacgacgagg gccgcgcgct gctcaaggcg ctgggcttcc 1620 cgttcaagac cgaccagtaa gacctccacg ccacaggtcc tccaccggtg aaccggtggc 1680 ggaaaccacg gcgagaaagg gcgtgaagca catgaccatg accgatcccg tcgcagacat 1740 gctgacccgt ctgcgcaacg caaactcggc ctaccacgac accgtgtcca tgccgtcctc 1800 gaagctgaag actcgcgtcg ecgagatcct caaggccgag ggctacatcc aggactggcg 1860 cgaggaggag gccgaggtcg gcaagaagct gaccatcgac ctgaagttcg gcccgcagcg 1920 tgagcgtgcg atcgccggcc tgcgccgcat ctccaagccg ggcctgcgcg tgtacgcga a 1980 gtccacgaac ctgccccacg tgctgggcgg cctcggcatc gccatcctgt ccacctcctc 2040 tggtctcctc acgaaccagc aggccgccaa gaaggctggc gtgggcggag aagtcctcgc 2100 •• ctacgtctgg tgacgggcaa gacggaagaa aggctgaact gacatgtctc gaatcggacg 2160 tctcccgatc accatccccg ccggcgtcga tgtgaccatc gacggcgacc gcgtctccgt 2220 aagggcccca gaagggcccc agggtcagct cgagcactcg ctgcccacgc ccatcacggc 2280 caccctcgag gaggggcagg tcaccgtgge ccgccccgac gacgagcgtg agtcccgctc 2340 cctqcacggt ctgacccgta ccctcatcag caacatggtc gagggcgtga ccaacggctc 2400 ctccaagcag ctcgaggtcg tcggcaccgg ctaccgcgtg caggccaagg gccaggacct 2460 cgactccgac ctgggctact cccacccc? C cccggtgaag gtgtcccagg gcatcacctt 2520 cacggtggag ggtaacaggg tcaccgtcgc cggtatcgac aagcagcagc aggtcggcga 2580 aacatccgca gaccgccgcc agctgcgccg ccccgacccg tacaagggca agggcgccta 2640 cgcgqqcsag cagatccgcc gcaaggccgg aaagaagtga tgtctactct gaaggtgaag 2700 ggcaagsgca agttcaacgc ccgcacccgc cgccacctcc gggtgcgcaa gcggatctcc 2760 ggcaccecgt ccgtcccccg cctcgtcgtc aaccgctctg cacggcacat gttcgtgcag 2820 gtcgtggacg acacgcagag ccgcacgatc gcgtacgcct ccaccacgga ggccgacgtg 2880 cgtgcgctcg agggtgacaa gacggccaag gccaagcgcg tgggcgagct cgtcgccgag 2940 egcgceaagg cggceggcat cgaggccgcg gtcttcgacc GGGCGG? caa caagtaccac 300C ggccgcgtcg cggccgtggc cgacggtgcg cgagagggtg ggctgcagcc gtgaccgaga 3060 acatcaacca gaaggacact caggtgaccg agagcaccga gaccaccgcc tccgagaccg 3120 ggtcgggctc gcgagccaga ccaccgagcg cgccaccggt ggccgcggcg gccgcgacgg 3180 cggccgcggt ggccggacgg cgatcgtcgt ggcggccgtc ggacgaccqa accgtcgtgg 3240 cgcccaggac gacgaggaag gaccagttcc tcgagcgcgt cgtgggcatc aaccgcgcct 3300 ccaaggtcgg ccgccgcttc tccttcaccg ccctcgcggt ggtgggtgac ggcgacggca 3360 ccgtcggcgt cggctacggc aaggcgaagg aggtccccgc tgcgatccag aaggccgtgg 3420 aggaggccaa gaagtccttc ttccgcgtcc cccgcgtcgg ctccaccatc ccgcacctgg 3480 tgcagggtga ggacgccgcc ggcgtcgcgc tgctccgccc ggcctccccg ggcaccgcgg 3540 tgatcgccgg cqgtccggtg cgcgccgtgc tcgagtgcgc cggcatccac gacgtgctct 3600 ccaagtccat gggctccgtg aacgcgatca acatcgtgcg cggcacggtg gagggcctca 3660 ? •• agaagctgaa gagcceccag gccgtcgccg cccgccgegg caaggccctg gacgagatcg 3720 ccccccatgc gacgctgcgc accatggaga acgatcgcgc ccagaaga c gcgaaggca_g 3780 gtqcgtgacg cgtgtttgag tccactegca agaacatcca gccctcg ae gccaccctgq 3840 tcatcacccu gacccgcggc gtcacgqgct ccaagcagaa ccatcggqac accctgcgct 3900 cgctggqccc g & agcggatc ggccaccagg tcacccgcaa ggccgacccg gtgacggtcg 3960 gcatggtcaa C3ccgtgcng cacctggtgt ccg ggagga ggtcaacaat ggctgacaac 4020 gacgccatca agqtccacga cccgcgtccg gcccccggtg ccaagaccgc caagacccgc 4080 gtggctcgcg ctgaggcgtc gaagggcaag accgccggtc gcggcaccaa gggeaccaag 4140 gttcqttace aggtccqtge gggcttcgag ggcggtcagc tgcccct? ca gatgcgrctg 4200 ccgaagetce gcsgcttcaa gaacccgttc cgcacgqagt accagqtcct gaacctggac 4260 aagttetccg cgcacttccc cgagggcggc gaggtcaccg tg? acgcqct cgtctccaag 4320 ggcctcgtcc gtcgfcggcca gcccgtgaag gtgctgggca cgggggagat caccgcggcc 4380 gtgcaggtga aggcgaacgc cttctctgcq tecgccgtgg agaagatcca ggeegccggc 4440 gggcccaccg aqicccLctq acacíjecgac ccatcgaccg agg gcecig .: ccggageagc 4500 cgcccgggcc aggccctggt ccgtccgtgt agactcgcac agecgccecc gtgtggccgc 4560 cgccccgcgc eeccgeeccg cggaacggcg cacgccccac aggacoagco gcaggagsac 4620 tcgcgcccaa ggccatcgcc cggatcgtcc ggacgcccga cctgttgcgg aagaccgcct 4680 tcacgctcgg gctcatcgcc gtctatcgga tgggcgactt cgtgccggcc accggcgtgg 4740 actacccggc ggtgcagcag tgcctggcag cgggcaacgc ccagggcggc ctgcactcct 4800 tcgtgaacat gttctcgggc ggggcgctcc tgcaggtgtc tgtcttcgcg ctgggcatca 4860 tgccgtacat cacggcgtcg atcatcgtgc agctgctgcg cgtggtgatc ccgcgcttcg 4920 agcagctcca ccaggagcgc cgcaggggcc aggcgacgct gacgcagtac acccgctacc 4980 tgaccctcgc cctcgccctg ctgcaggcga ccacgatggc ctcgctggcc cgcaccgggg 5040 ccctgctcgg atgcagcctg ccgctgctgc gcgacggctc catcctcacg gtgctgctcg 5100 tggtc2ccgc cctgaccacc ggctgtctca tcgtcatgtg gttcggggag cggatcaccg 5160 agaacggcgt gggcaacggc atgtccctgc tcatcttcac ctccatcgcg gcaggcttcc 5220 •• cggccggtct cggccaggtg gtccagacgc agggctggcg cgtgttcgcg atcgtcatgg 5280 ggatcggcct gctcaccatg ctggccatcg tcttcgtgga ggagtcgcag cgccggatcc gccaacgtca tcccggtcat cttcgcctcc tccgtgctga 5460 tgctcccggg catcctcatc cgccgcagga cagttcaaca cggcagtgcg ccggccccgt 5520 ggatcacgtg gctgagccgg tacttcggct ccggtgacca cccggtgtac atggccctgt 5580 acttcctgct catcatcggc ttcacgtact tctacgtgtc catcacgttc aacccggtgg 5640 acatctcgga caacatgaog cgctacggcg gcttcatcec ggcgtccgcg ccggccggcc 5700 ceaccgagcg ttacctgcag tacgccatca gccgcatcac gttcgCggtg ggggccccct 5760 acctcggtat cgtggccatg atcccgctga tcgccttcgc ggtgatcggc accagccaga 5820 accccccgct cggcggcacg tccatcctca tcatggtggg cgtcggcctc cagaccgcga 5880 agcaggtcag cgcacagacg gagcagcgcc actacgaggg cctgccgcgc tgagccccga 5940 caacgccqtc cccgaccccg cgtatcgaca gtgaggaaca cacgatgacc cgcatgccgc 6000 tcatqggccc tcccggctcc ggcaagggca cccaggccac ccggatcgca gacaagctgg 6060 ggatcocccc gatctccacc ggtgacatct tccgccacaa cgtgaagtcg atgacg cgc 6120 tcggogtcga ggccaagagg tacatcgaca acggcgactt cgtccccgat gaggtcacga 6160 accgcstggt cgccgaccgc atcgcccagg ccgacgcgga gcacggcccc ctgctqgacg 6240 gctacccgcg ca cgaagggc caggtcgagg cgctggacgc catgctcgcc gaggccggcc 6300 agtcgccgtc cgccgtcgtc gagctggagg tgcccgacga ggagctcgtg gagcgcctgc 6360 tcaagcgtgc cgagatcgag ggccgcgcgg acgacaccca ggaggtcatc gagcacegcc 6420 tggacctgta ccaccgcgag accgagtccg tcatccagga gtacgtggag cgcggcatcg 6480 tcgcccgcgt ggacggcacc ggccagatcg acgacgtcac cgagcgcctg ctgcaggccg 6540 tgtactccgt gcgctccgcc acgggctccc tgcccgtgat ccagccgggc gcggagtcct 6600 gaccccgtga tcggccgccg ctcgctcgag ctcaagaccg ccccccagct gctggccatg 6660 cagcgcgcgg gggtggtcct gtccgaggca ctggacgccg cgctggccgg cgcgccgggc 6720 ttcaccaccg cggagctgga cgccgtgttc gcggtggtgc tggccgaacg cggtgcgacc 6780 •• tccaacttcc tgggctacta cgacttcccg gcctcgatct gcacctcggt caacgaggag 6840 gtcgtgcacg gcatcccc 6858 < 210 > 42 < 2ll > 578 < 212 > DNA < 213 Homo sapiens < 220 > < 221 > N0 IS SAFE < 222 > (5) < 223 > It can be any nucleic acid S INSURANCE < 223 > It can be any nucleic acid < 220 > < 221 > IT IS NOT INSURANCE < 222 > (31) < 223 > It can be any nucleic acid < 220 > < 221 > IT IS NOT INSURANCE < 222 > (48) < 223 > It can be any nucleic acid < 220 > < 221 > IT IS NOT INSURANCE < 222 (211) < 223 > It can be any nucleic acid < 220 > < 221 > IT IS NOT INSURANCE < 222 > (292) < 223 > It can be any nucleic acid < 220 > < 221 > IT IS NOT INSURANCE < 222 > (308) < 223 > It can be any nucleic acid < 220 > < 221 > IT IS NOT INSURANCE < 222 > (350) < 223 > It can be any nucleic acid < 220 > < 221 > IT IS NOT INSURANCE < 222 > (384) < 223 > It can be any nucleic acid < 220 > < 221 > IT IS NOT INSURANCE < 222 > (477) < 223 > It can be any nucleic acid < 220 < 221 > IT IS NOT INSURANCE < 222 > (507) < 23 > It can be any nucleic acid < 220 < 221 IS NOT SECURE < 222 >; 529) < 223 > It can be any nucleic acid < 220 > < 221 IS NOT SECURE < 222 > (54 9 i <223> Can be any nucleic acid <220> <221> IS NOT SECURE <222> (551) <223> Can be any nucleic acid <220 > <221> NOT SAFE <222> (558) <223> Can be any nucleic acid < 400 > 42 ttctngccca Cggcagagat ggncaggttg ncgttgagca ggtactgnc; atcagccgtc 60 ttcagcgcca ggtagttccc atcgttctgc acacccgggt ggctccgctg cttcacgtca 120 ataccagtgg caccagctgg gatggtgaca atgtcattgt agccataatc ggtgggggtg 180 agggacccgg agaccttcct gcaggagttg nctttgcccc cacacaccce gcatttgtcc 240 agcttccgag gcgagtccac cacatggtca cagccggcct tgacacactg gncacggaca 300 cagatggnca gtgtttctgg cccacacagg gtgccatcaa tcaccttggn ctcgaacact 360 ttggaactcg ctcctccccc gggntcggga ggaacaactt gcaggggtec cgggggggac 420 aacccagcat tcttggggga cccactgcag gaggattccc cgtccatgtc aagtgtnatt 480 ggtgggcatt attcttctca caattgntgc tccctgaagg ttttcccgnc aaggggggat 540 tcccccccng ntggaatnat tggtacttgg gtctccga 5-78 < 210 > 43 < 2il 305 < 212 > & DN •• -i213 Kopio sapiens < 220 > < 221 > IT IS NOT INSURANCE < 222 > (12B) < 223 > It can be any nucleic acid < 220 > < 221 > IT IS NOT INSURANCE < 222 > (146) < 22 > It can be any nucleic acid < 400 43 catttaagtt tgctagtcct ttgcaaacag actgacgctg agtgtcctgt ctgagtcaat 60 aagtgcactt ttacctttta acctatgccc Lctacttgaa cccgagcaag gtccagtcca 120 ctggacangt tgatgatagg gtctgpcgcc ccataccctc tccccttccc cctcaggaat 180 ttgtgcagta ctggaggggt tgeggcaatg ggaggcctgg gtgggccgtg ctgccttgat 240 gacccagtca atggccaagg ccacagtgqa gacccttgtc tgcacctcag taccgcatgt CCAGG 300 305 210 > 44 < 211 > 333 < 2I2 DNA < 213 > HO? Sapiens < 221 > < 221 > IT IS NOT INSURANCE < 222 > (82) < 222 > It can be any nucleic acid < 22C > < 221 > IT IS NOT INSURANCE < 222 > (255) < 223 > It can be any nucleic acid < 220 > < 221 > IT IS NOT INSURANCE < 222 > (275) < 223 > It can be any nucleic acid < 220 > < 221 > IT IS NOT INSURANCE < 222 > (299! <223> Can be any nucleic acid <22C> <22i> NOT SAFE <222> (313) •• <223> Can be any nucleic acid < 22C >; <221> NOT SAFE <222> (324) <223> Can be any nucleic acid <400> 44 ggcacaggtg actttaqcat gcagagcagc aaagagagag caaccaccaa catcatccag 60 ccgctgctcc acgcacagtg gntgctgggg gactggtctg agtgctctag cactgcggcrg 120 ccggctggca gaggcgaact gtaga ? tgca gggacccctc cggtgcaggc ctctgccacc 180 tgcaacaagg ctctggaaac ccgaggatgc caagccctgg cagaaccagc tgtgceccct 240 ggggncaggg gccaccttgt gctcngggac atgcggtaat ggaggttgnc 300 ttncattgtg gtgnatgggt tcc 333 <; 21C > 45 < 211 > 102 < 212 DNA < 215 > Unknown < 22 > < 223 > Description of the Unknown Body: Unknown < 4C > 45 < 220 > < 221 > IT IS NOT INSURANCE < 222 > (64) < 223 > It can be any nucleic acid < 220 > < 221 > IT IS NOT INSURANCE < 222 > (69) < 223 > It can be any nucleic acid < 220 > < 221 > OR IT IS SAFE < 222 > (71) < 223 > It can be any nucleic acid < 220 > < 221 > IT IS NOT INSURANCE < 222 > (72) < 23 > It can be any nucleic acid gcagcagcag cgcagcgcag agagagcagc agcagcagca gcagcagcag cagagcagat 60 cntnctggna nnaaaaaatc gcggcagcag ctgctctagc ag 102 < 210 > 46 < 2ll > 123 < 212 > DNA < 2i3 > Unknown < 220 > < 223 > Description of the Unknown Body: Unknown < 220 > < 221 > IT IS NOT INSURANCE < 222 > £ 9) < 223 > It can be any nucleic acid < 220 > < 221 > IT IS NOT INSURANCE < 222 > (51) < 223 > It can be any nucleic acid < 220 > < 221 > IT IS NOT INSURANCE < 222 > (52) < 223 > It can be any nucleic acid < 220 > < 221 > IT IS NOT INSURANCE < 222 > (57) < 223 > It can be any nucleic acid < 220 > < 221 > IT IS NOT INSURANCE < 222 > (67) < 223 > It can be any nucleic acid < 220 > < 221 > OR IT IS SAFE < 222 > (123) < 223 > It can be any nucleic acid < 400 > 46 caggcaagnc ggcacgtagg agcagcagca gcagcagcag cagcagtaac nnagtcnacg 60 agggggngcc cgggacccaa ggcgcccgaa cagagaggcg gagcacaatc cactggtcgg 120 cgn 123 < 210 > 47 < 211 > 109 < 212 > DNA < 213 > Unknown < 220 > < 223 > Description of the Unknown Body: Unknown < 220 > < 221 > IT IS NOT INSURANCE < 222 > (87) < 223 > It can be any nucleic acid < 220 > < 221 > IT IS NOT INSURANCE < 222 > (95) < 223 > It can be any nucleic acid < 220 > < 221 > IT IS NOT INSURANCE < 222 > (102) < 223 > It can be any nucleic acid < 220 > < 221 > IT IS NOT INSURANCE < 222 > (106) < 223 > It can be any nucleic acid < 220 > < 221 > IT IS NOT INSURANCE < 222 > (107) < 223 > It can be any nucleic acid < 400 > 47 ggcacgcagg agcagcagca gcagcagcag cagcagcagc agagagagag cagcagagag 60 agagascagc agagcagagc agagcanagt agagnagagc anagcn? Ac 1 09 < 210 > B < 211 > 293 < 212 > DNA < i3 > Homo sapiens < 220 > < 221 > IT IS NOT INSURANCE < 222 > (86) < 223 > It can be any nucleic acid < 220 > < 221 > IT IS NOT INSURANCE < 222 > (166) < 223 > It can be any nucleic acid < 220 > < 22I > IT IS NOT INSURANCE < 222 > (185) < 223 > It can be any nucleic acid < 22C > < 221 > IT IS NOT INSURANCE < 222 > (209) < 223 > It can be any nucleic acid < 220 > < 221 > IT IS NOT INSURANCE < 222 > (214) < 223 > It can be any nucleic acid < 220 > < 22i > IT IS NOT INSURANCE < 222 (219) < 223 > It can be any nucleic acid < 220 > < 221 > IT IS NOT INSURANCE < 222 > (234) < 223 > It can be any nucleic acid < 220 > < 221 IS NOT SECURE < 222 > (290) < 223 > It can be any nucleic acid < 400 > 48 ggcacgaggg ggaaactgct ccgegcgcgc cggggaggag gaaccgcccg gtcctttagg 60 gtccgggccc ggccgggcat ggattnaatg cctgagcccg ggtcccgctg tcttctgcct 120 ctteecctgc tgctgctgct gctgctgctg ctgccggccc cggagntggg cccgagccag 180 gccgnagctg aggagaacga cttgggttng cctncccana aaacgggaag ggar.ttgggg 240 ttaatcgaag tcattgggac cattttaaaa ggggcttcct ggattaca n etc: 3 < 210 > 49 < 211 > 506 < 212 > DNA < 213 > Homo sapiens < 220 > < 221 > IT IS NOT INSURANCE < 222 > (283) < 223 > It can be any nucleic acid < 220 < 221 > IT IS NOT INSURANCE < 222 > (342) < 223 > It can be any nucleic acid < 220 > < 221 IS NOT SECURE < 222 > (356) < 223 > It can be any nucleic acid < 220 > < 221 IS NOT SECURE < 222 (362) < 223 > It can be any nucleic acid < 220 > < 221 > IT IS NOT INSURANCE < 222 > (364 < 223 > it can be any nucleic acid < 220 > < 221 > it is NOT SECURE < 222 > (368) < 223 > it can be any nucleic acid < 220 > <; 221> IS NOT SECURE <222> (429) <223> Can be any nucleic acid <220> <221> IS NOT SECURE <222> (454) <223 >Can be any nucleic acid <220 <221> NOT SECURE <222> (461) <223> Can be any nucleic acid < 4D0 > 49 aatccggcae gageacccgg ccactgcagt cttctgccct gctggacagc agcagcagca 60 gcaqcegcag cagcagcagc agcageaaca gtaacagcag cagttcgtcc ggacccaacc 120 cttecacctc ctCCgagccc accaaggcag accccacagg tgctttggaa ctccccaaag ISO agctgccaga aatctttgat cccacacgag agtgcatgag ctcggagctg ctggaggagt 240 tgatgccctc agaagtgttt gcccctctgc tttcgtcttt ctncaccccc gggagaccac 300 gattatatct acaacctgga cgagagtgaa ggtgtttgtg apctcttttg atgtgnctgt 360 tntnaacntt tgactgacag ggacatgcct tttttgqttg ggacccagat tttttgactt 420 gggggtttnc ttgggacttt tcaaccgacc ctanagagtt nagagcaaan aggttggttt 480 ttcggcttcc ttaacgaaag ttttgg 506 < 210 > 50 < 211 > 419 < 212 > DNA < 213 > Homo sapiens < 220 > < 221 > IT IS NOT INSURANCE < 222 > (137) < 223 > It can be any nucleic acid < 220 > < 221 > IT IS NOT INSURANCE < 222 > (221) < 223 > It can be any nucleic acid < 22C > < 221 > IT IS NOT INSURANCE < 22 (259) < 223 > It can be any nucleic acid < 22C > < 221 > IT IS NOT INSURANCE < 222 > (327) < 223 > It can be any nucleic acid < 220 < 221 > IT IS NOT INSURANCE < 222 > (385) < 223 > It can be any nucleic acid < 220 < 221 > IT IS NOT INSURANCE < 222 > (389) < 223? It can be any nucleic acid < 220 > < 22i > IT IS NOT INSURANCE < 222 > (416) < 223 > it can be any nucleic acid < 22C > < 221 > OR IT IS SAFE < 222 > (418) < 223 > It can be any nucleic acid 40D > 50 ttcaaqcacc aaaacttgtg ttttaatgat gttggatgga aatctttcct aaatgtgtca 60 tgcatgctct tgtctccctt aatggagaga gtgtgacact gcttagc = ct tggatggctt 120 ggggtggtgg ttatgancag cagtctgtca cagctcagcg aggtgaagcc tgtgggcgtt 180 ttgctctgtg ctgaacggct cagtggccct acaaagcgga ntcagctcrt ggtggctttc 240 tgttgcggtg ggctgctgnt gctgctgctg ctgctgctgc tgctgccctt gcctctaaaa 300 gaactcactt cctcttcctc ctgctgncac ctgtcttttg gcttgtggga ttggagtcat 360 sgggcccaga tggagccttg ctccntgant tatgataggc ccctcggtct cttttntnc 419 < 210 > 51 211 > 495 < 212 > DNA < 213 ^ > Saccharomyces cerevisiae < 220 > < 221 > IT IS NOT INSURANCE < 222 > (177! <223> Can be any nucleic acid <220> <71 \> NOT SECURE <222> (322) <2 3 It can be any nucleic acid <22C> < 22i> NOT SAFE <222> (328) <223> Can be any nucleic acid <220> &22;; It can be any nucleic acid < 220 > < 221 > IT IS NOT SECURE <: 222 > (368) < 2 3 > It can be any nucleic acid < 220 > < 221 > NO IT IS SAFE <222 (371) <223> It can be any nucleic acid < 22D > < 221 > OR IT IS SAFE < 222 > (375) < 223 > It can be any nucleic acid < 220 > < 221 > IT IS NOT INSURANCE < 222 > (380) < 223 > It can be any nucleic acid < 220 > < 221 > IT IS NOT INSURANCE < 222 > (386) < 223 > It can be any nucleic acid < 220 > < 221 > OR IT IS SAFE < 222 > (396) < 223 > It can be any nucleic acid < 220 > < 221 > IT IS NOT INSURANCE < 222 > (404) < 2 3 > It can be any nucleic acid < 220 > < 221 > IT IS NOT INSURANCE < 222 > (423) < 223 > It can be any nucleic acid < 220 > < 221 > IT IS NOT INSURANCE < 222 > (426) < : 223 > It can be any nucleic acid < 22C > < 22i OR IT IS SAFE < 222 > (436) < 223 > It can be any nucleic acid < 220 > < 221 > OR IT IS SAFE < 222 > (443) < 223 > It can be any nucleic acid < 22C > < 221 > IT IS NOT INSURANCE < 222 > f456) < 223 > It can be any nucleic acid < 220 > < 221 > IT IS NOT INSURANCE < 222 > 460) < 223 > It can be any nucleic acid < 220 > < 221 > IT IS NOT INSURANCE < 222 > (467) < 223 > It can be any nucleic acid <; 220 > < 221 > IT IS NOT INSURANCE < 222 > (468) < 223 > It can be any nucleic acid < 220 > < 221 > IT IS NOT INSURANCE < 222 > (471) < 2 3 > It can be any nucleic acid < 220 > < 221 > IT IS NOT INSURANCE < 222 > í'474) < 223 > It can be any nucleic acid < 400 > 51 aattcggcac gagcaaagtt ctgcgctcca ttgtgggcat caaacgacac gtcaaagcce 60 tccatctggg ggacacagtg gactctgatc agttcaagcg ggaggaggat ttctactaca 120 cagaggtgca gctgaaggag gaatctgctg ctgctgctgc tgctgctgcc gcagacnccc 180 egtccctggg actcccacct ccgagccagc tcccaccccc agcatgaccg gcctgcctct 240 gtctgctctt ccaccacccc Ctgcacaaag cecagtcctc cggcccagaa catcctgggc 300 ccsgagttcc ttcctt? Cr.t tnaggggntt ttcagcaagt tpagttcctt gggtcctttt 360 tgggaaantt naggnagttn aaqgantacc aggttnttgc oatpctctto agatccaagt 420 ttnacnaaaa atttcnaaca gtntaaattg ggtttntcgn ccccttnpcg nggntgtttt. 480 ttttttcggg tccgg 495 < 210 > 52 < 2H > 81 < 212 > DNA < 213 > Unknown < 220 > < 223 > Description of the Unknown Body: Unknown < 220 > < 221 > IT IS NOT INSURANCE < 222 > (65) < 223 > it can be any nucleic acid < 22C > < 221- > IT IS NOT INSURANCE < 222 > (67) < 223 It could be any nucleic acid ^ 220 < 221 > IT IS NOT INSURANCE < 222 (71) < 223 > It can be any nucleic acid < 220 > < 221 > IT IS NOT INSURANCE < 222 > (75) < 223 > It can be any nucleic acid < 400 > 52 ggcacgcagg agcagagcag cagcagcaga gagagcagca gcagcagcag cagcagcaga 60 gagananata natanatata t. 81 < 210 > 53 < 2il > 305 < 212 > DNA < 213 > Homo sapiens < 220. > < 221 > IT IS NOT INSURANCE < 222 > (11) < 223 > It can be any nucleic acid < 220 < 221 > IT IS NOT INSURANCE < 222 > (62) < 223 > It can be any nucleic acid < 220 > < 221 ^ IT IS NOT INSURANCE < 222 > (81) < 223 > It can be any nucleic acid < 220 > < 221 > IT IS NOT INSURANCE < 222 > (256) < 223 > It can be any nucleic acid < 220 > < 221 > IT IS NOT INSURANCE < 222 > (289) < 223 > It can be any nucleic acid < 400 > 53 aggeacttga nttgaaaatg gaaaacccta ctgctggtgg tgctgcggtg atgaggccta 60 tnatgcagcc ccagggtttt pttaatgctc aaatggtcgc ccaacgcacc agaaagcrgc 120 cccccgacaa taagccatca 'cagagggcgg ccataatgat gcagcagcag cageagcage ISO aacagcagca gcagcagcag cagcagcagc gcaacagcaa aacagcaaca cagcagoaac 240 agcagcaaac ccaggncttc agcccacctc ctaatgtgac tgcttcccnc agcatggacg ggctt 300 305 < 210 > 54 < 211 > 307 < 212 > DNA < 213 > Vi Hepatitis C Virus < 220 > < : 221 > IT IS NOT INSURANCE < 222 > (212) < 223 > It can be any nucleic acid < 40C > 54 tggggtgtga agctccggtg ctggtgcggc gggggactgc ggggccagcc tcagt ttaaa 60 ccccctcagc agtctttctg tcgttgccct ccacactgcg agactctgga gggcgatctg 120 gaggtctgga agataaccga t tcctgggag atttgggggt agtctccaac ctgtccccgg 180 ctcaccttgc gacccgaagc cggcggcctt gncaggagta ttctagaatg agtgcacata 240 aaaatacct t caaacggtag cagcagcagc agcagcagca gcagcaagca gcagcagcag 300 cagcs? C 307 < 210 > 55 < 211 > B8 < 212 > DNA < 213 > Unknown < 22C > < 221 > IT IS NOT INSURANCE < 222 > (6) 223 ^ It can be any nucleic acid < 220 > < 221 > IT IS NOT INSURANCE < 222 > (7J <223> Can be any nucleic acid <22C> <221> IS NOT SEGTTRO <222> (78) <223> Can be any nucleic acid <220 > < < 223 > 22i> NOT SECURE <222> (83) <223> Can be any nucleic acid <220> <221> IS NOT SECURE c222> (B7) <223> Can be any nucleic acid < 220 > < 223 > Description of the Unknown Body: Unknown < 400 > 55 ggacanr.gac tactctctct ctctctctct ctctctctgc tgctgccgct gtgctgctgc 60 tgctgctgct gctgccgntg tgngcana 88 < 210 > 56 < 211 > 346 < 212 DNA < 213 > Unknown < 220 > < 22i > IT IS NOT INSURANCE < 222 (278) < 223 > It can be any nucleic acid < 220 > < 221 > IT IS NOT INSURANCE < 222 > (288) < 223 > It can be any nucleic acid < 220 > < 221 > IT IS NOT INSURANCE < 222 (299) < 223 > It can be any nucleic acid < 220 > < 22i > IT IS NOT INSURANCE < 222 > (313) < 223 > It can be any nucleic acid < 220 > < 221 IS NOT SECURE < 222 > (342) < 223 > It can be any nucleic acid < 220 > < 223 > Description of the Unknown Body: Unknown < 400 > 56 ggcacagccc aactggtgat gctgctgceg ccgccgctgc cgccgccgco gcccctattq 6C ctcstactct agtggggctg gaagggt gt tcctactcgc accaccgcci = ccagagaca 110 gagggaaaaa eaaaaccggc agccactgct gaatgtcggg ttcggaggct gcatccgact 180 cggtcacaag gaaaatggat tcagtttcca tctctccctc ctttaaacag cttctccggg 240 tctcagcacg sgcttccagg gcagcgatcg aggagacntt accaaggngc accacacapt 300 agatgctgag acntcgtgac tccaggataa gaaacattaa cngggg 346 < 210 > 57 < 2¿1 > 496 < 212 > DNA < 213 > Unknown < 220 > < 223 Description of the Unknown Body: Unknown < 220 > < 22I > IT IS NOT INSURANCE < 222 > (II) < 223 > It can be any nucleic acid < 220 > < 221 > IT IS NOT INSURANCE < 222 > (78) < 223- > It can be any nucleic acid < 220 > < 221 > IT IS NOT INSURANCE < 222 > (195) < 223 > It can be any nucleic acid < 220 > < 221 > IT IS NOT INSURANCE < 222 > (197) < 223 > It can be any nucleic acid < 220 < 22i > IT IS NOT SECURE 222 > (286) < 22Z > It can be any nucleic acid < 22C > < 221 > IT IS NOT INSURANCE < 222 > (291) < 223 > It can be any nucleic acid < 220 > < 22a > IT IS NOT INSURANCE < 22I (293) < 223 > It can be any nucleic acid < 221 > < 221 > IT IS NOT INSURANCE < 222 > (315) < 213 > It can be any nucleic acid < 22C > < 221 > IT IS NOT INSURANCE < 222 > (328) < 223 > It can be any nucleic acid < 220 > < 221 > IT IS NOT INSURANCE < 222 > (329) < 223 > It can be any nucleic acid < 220 < 221 > IT IS NOT INSURANCE < 222 > (344) < 223 > It can be any nucleic acid < 220 < 221I IS NOT SAFE < 222 > (346) < 223 It can be any nucleic acid < 220 > < 22i > IT IS NOT INSURANCE < ?. ?? > (352) < 223 > It can be any nucleic acid < 220 22i > IT IS NOT INSURANCE < 222 > (354) < 223 It can be any nucleic acid < 220 > < 22i > IT IS NOT SECURE 222 > (3531 <223> Can be any nucleic acid < 20-- < 2 1 ^ IT IS NOT SECURE < 212-- (366. < 2 3 > It can be any nucleic acid 220 < 22i > IT IS NOT SECURE 22 > (399) < 223 > It can be any nucleic acid < 220 > < 22i > IT IS NOT INSURANCE < 222 > (406) < 223 It can be any nucleic acid < 220 > < 221 > IT IS NOT SECURE 2Z2 > (410) < 223 It can be any nucleic acid < 220 > 221 > IT IS NOT INSURANCE < 222 > Í418) < 223 > It can be any nucleic acid < 220 > < 221 > IT IS NOT INSURANCE < 222 > (420) < 223 > It can be any nucleic acid < 220 > 221 > IT IS NOT INSURANCE < 222 > (435) < 223 > It can be any nucleic acid < 220 > < 221 > IT IS NOT INSURANCE < 222 > (443) < 223 > It can be any nucleic acid < 220 > 221 > IT IS NOT INSURANCE < 222 > (453) < 223 > It can be any nucleic acid < 220 > < 221 > IT IS NOT INSURANCE < 222 > '¿¿¿L < 223 > It can be any nucleic acid 220 > < 221 > IT IS NOT INSURANCE < 222 > (459) < 223 > It can be any nucleic acid < 220 < 221 > IT IS NOT INSURANCE < 222 > (471) < 223 > It can be any nucleic acid < 220"'<221> NOT SAFE <222 ~> 73 <223> Can be any nucleic acid < 220 > < 22i > IT IS NOT INSURANCE < 222 > (474) < 223 > It can be any nucleic acid < 220 > < 221 > IT IS NOT INSURANCE < 222 > (481) 223 > It can be any nucleic acid < 400 > 57 naggtgcaca gaattcggea gatgtggtgg atggggaggg eegcacgoga cagaagttct 6C ccctgtgrat tctgacgnct gagaaaggag cacttcatcc GGGCGG = gac caaggaaatc 12C gtcaatgggt ggctggagat gctcatggtc tatccccgga ccaacaagca gaatcagaag 180 aagaaacgga aagtngnagc cccccacacc acaggagcct gggactgcca agttgqgctg 240 ttaccagcag cagcagcagc agcagcagca gcagcagcat ccccantgct ntnggaaagt 300 aagtnccaca tcccaccacc atttgggnna aaaccaaggt tgtngnagac gngntttngg 36C gatttnggca ttgcgggttg cttgcatgga aggacattng gttgtnggtn ccttggangn 420 tacaattacc atctncggtt gtnaaggtta aanntccgnc attcagaagg ptnnaaggtg 460 ntttgaagtc catttg 496 < 210 > 58 < 211 > 268 < 212 > DNA < 213 > Drosophila sp. < 220 > < 221 > IT IS NOT INSURANCE < 222 > (16) < 223 > It can be any nucleic acid <; 220 > < 221 > IT IS NOT INSURANCE < 222. »(51) < 2 3 > It can be any nucleic acid < 220 > < 221 > IT IS NOT INSURANCE < 222 > (60) < 223 > It can be any nucleic acid 220 > < 221 > IT IS NOT INSURANCE < 222 > (202) < 223 > It can be any nucleic acid 400 > 58 aacacCCatc cttganagct ctgcttggga agcaggacaa agctatatgt naggaaactn 60 tggagcctcc gcagactctc caccagcagc agcagcagca gcagcegcag caagagaagc 120 ttccaattag gcagggggtc gtacqctccc tgtcctacga qgaacccaga agacactcac 180 cccccattga gaagcagctc tptocagcca ttcagaaact catcgtcagg agcgcagacc 240 tccacccatt gccagagctg cctgaaaa 268 < 21C > 59 < 211 > 471 < 212 > DNA < 213 > Homo sapiens < 220 > < 221 > IT IS NOT INSURANCE < 222 > (249) < 223 > It can be any nucleic acid < 220 > < 221 > IT IS NOT INSURANCE < 222 > (386) < 223 > It can be any nucleic acid < 220 > 2 i ^ NOT SAFE < 222 > (449) < 223 > It can be any nucleic acid < 400 59 tcgacccacg cgtccgctga ggaacegacg ttccctggcg gccctggcgc cctcaaaccc 60 agacatgctg ctgctgctgc tgctgctgcc cctgctctgg gggacaaagg ggatggaggg 120 agacagacaa tatggggotg gttacttgct gcaagtgcag gagctggtga cggtgcagga 180 gg? Cctgtgt gtccatgtgc cctgctcctt ctcctacccc caggatgget ggactgactc 240 tgacccagnt catggctact ggttccgggc aggagacaga ccataccaag acgctccagt 300 ggccatsaac saoecagaca gagaagtgca ggcagagacc cagggccgat tccaactcct 360 tggggacatt tggagcaacg actcjcnccct gagcatcaga gacgccagga agagggataa 420 ggggccatst ctctttcggc tagagaganq aagcatgaaa tggagttací a 471 < 210 > 60 < 211 379 < 212 DNA < 213 Unknown < 220 > < 223 > Deeming the Unknown Body: Unknown < 220- > C22i > IT IS NOT SECURE c222 (2) < 223 It can be Any nucleic acid < 220 < 221 > IT IS NOT INSURANCE < 222 > (14) < 223 > It can be any nucleic acid < 220 > < 221 > IT IS NOT INSURANCE < 222 > (31) < "2 3> Can be any nucleic acid <220> <221> IS NOT SECURE <222> (135) <223> Can be any nucleic acid <220> < 221 >IT IS NOT SECURE <222> (315) <223> It can be any nucleic acid <220> <221> IT IS NOT SAFE <222 ^ (332) • '21'3 It can be any nucleic acid <220> <221 IS NOT SECURE <222> (349) <223 It can be any nucleic acid <220 <221 IS NOT SAFE <222 (357) ^ 3> It can be any nucleic acid <r220:> 22 i- NOT SAFE <222> (374) <223> Can be any nucleic acid 60 ar.ccc l00? SRG agqnaaggga gagggtgacc nqcatcccaa gtggagtgaa ctagacccca 60 gttcaggagg catqgagctg acaaccatga ggcctcggca gccaccgoca ccaccgccgc 120 cgccaccacc gtagr.cagca gcagcagcag cagcagcagc aagagtcaac tctgacttag 180 cgaatagaga cagccagaga gaaacgtgat caacgaagga gacatctgga gtgtqcgcgc 240 • -ccttcagag gggacgggtg atgggcagat ttggaaaaag caccgcagat tqggaacctt 300 aiitttutt tttcntaaaa ttgttgttdt gnaaatttgg? Tttttcepg taacttntta 360 aaaacttaaa agtngcctt < 21C > 61 < 21i > 255 < 212 > DNA < 213 > DeBsonocido < 220 > < 223 > Description of the Unknown Body: Unknown < 220 > < 221 IS NOT SECURE < 222 > (121) < 223 > It can be any nucleic acid < 220 > < 221 > IT IS NOT INSURANCE < 222 > (183) < 223 > It can be any nucleic acid < 220 > < 221 IS NOT SAFE 222 ^ (254) < 223 > It can be any nucleic acid < 220 > < 221 > IT IS NOT INSURANCE < 222 > (25b) < 223 > It can be any nucleic acid 400 > 61 aatcccgaca atggaaagca ctcttagcct tgcagtggtc tacattttta aggaaccaat 60 stttcagcat tctttattac ccggcacgct gtgtcctttg tcagagctca agtttatggt 120 nactgccagg gtcagacaqc ccatttgctg ccgctgctgc tgctgctgct ttctcgaact 180 ggnatggcat tagggaagct gctgtctgag tgttegggae tgtcttggct aagtaaagce 240 255 aacgtccttt cctnn < 210 > 62 < 211 > 5289 < 212 > DNA < 213 > Unknown < 220 > < 223 > Description of the Unknown Organism: Unknown -400 > 62 cgagctctcc cagccgcagc ctccgaatcc acggccccca ccccgcqcct ctccagcgct 60 CCAC rccgcc gctgcgccct tgccgccggc cccggccgcc gcatccgcgc cocca taggc 120 TCCT tgctgg gcacaaat ag ctccaccatg gggctggcct sgggactcgg cgtcccccc c 180 ctgt tgcatg cctgcggctc caaccgcatt ccagagt ctg ggggagacaa cagtctgttt 240 gacatctttg aactcaccgg agctgcccgc aagcggtctg ggcgccgact ggtgaagggc 30C cctgaccctt ctagcccagc tttccgcatc gaggatgcca acctgatccc ccctgtgccc 360 gacaagaagt tccaagacct agtggatgct gtgcgggcgg agaaaggtc t cctcctcctg 420 gcctccctga ggcaaatgaa gaagacccgg ggtaccctgc tggctgtgga gcggaaagac 480 cact ctggcc AGGT cttcag cgtgatctcc aatggcaagg cgggcaccct ggacctgage 540 ctgaccgtgc aggggaagca gcatgtggtg tcggtggaag aagcactcct ggcgactggc 600 cagtqgaaga gcatcaccct gtttgtgcag gaggacaggg cceagetgta catcgactgt C63 gagaaqatgg agaatgcgga gctggatgtc CCCat gca ccaga t ct tcac cagggacctg ^ 20 gccageatcg ccaggctccg cattgccaaa ggaggtgtca acgacaat tt ccagggggtg 780 ctgcagaac g taaggtttgt ccctggaacc acaccagaag acatcctca g gaacaaaggc 840 tgctccagct ctaccagtgt ctttgtcacc cttgacaaca acgtggt? aa tgggtccagc 900 GCA cctgccaccc ccgacta cattggccac aagacaaagg acctgcaagc cacecgtggc 960 atctcatgrg acgagctgtc cagcatggtc ctggagctca ggggt ctacg caccatcgcg 1 C20 accacgctgc aggacagtat ccgcaaagcg accgaagags acaaagagct gqccaacsag 1080 ctgaggaggc ccccactctg ctaccacaac ggagtgeagt acagcaccgg cgacgagtgg 1140 acgqcggaca qctgcact ga gtgtcgctgo cagaact cag tt accatctg caaaaaagcg 1200 tctt gtccca tcatgccctg ctccaatgcc acagt tccgg atggagaat g ctgcceacgg 126C tgcc ggccca gcgact CTGC agacgatggc tggtccccgc ggtctgagc g gacctcctgc 1320 tctgtgacct gtggcaatgg aatccagcaq cgtggccgct cctgcgacag 1380 cctcaacaac aq? cgcgdgg gctcctctgt gcagacgcgg acctgccaca cccaqqagt tgacaagaga 1440 g tt taaacagg atggcggctg gagccactgg tccccatggt catcttgct c cgtaacatgt 15C0 ggagacggtg t gatcacaag gatccggctc tgcaact ccc ccagccccca gatg. atggg 1560 aagceacgtg agggcaaaac ccggqagacc aaagcctgcc auaaagactc ctqccccat c 1620 aatggaggoc ggggacct tg gtcaccatgg gacatct GTT ccgtca CCCG cagaggaggg 1680 gt'acagaaao gtagccggct ctgcaacaac cccaaacccc AGT GTT ttgcagg oaagaaccsc January 40 ggtgatg tgacagaaaa ccagatctgc aacaagcagg actgtcccat tgacggatgc 1800 ccgtccaacc cctgctttgc tggtgtccag tgtaccagct accctgacgg cagctggaag? 86C t? cggcgccc gtcccccagg ctatagtgga gatggagtcg agtgcaa = ga cgttgatgag 1920 tqcaaagaag tccctgatgc ctgcttcaac cacaatggag agcacaggtg tgagaacaca 1980 acaactgcct gaccccggct ccgcgcttca gccctgccca ctggcccgca gcccttcggc 2040 cgcggcgtgg aacatgccac cgccaacaag caggtatgca agccccgaaa cccctgcaca 2100 gacgggac = c acgacCgcaa caagaacgcc aagtgcaact acctgggcca ctacagcgac 2160 cceacccscc gccgcgagtg caagcctggc tacgccggca acggcatcat ctgcgggsag 2220 gac = cagacc tggacggctg gcccaatgag gacctgctgt gcgcggccaa cgcaacttac 22S0 cactgcaga = aggataat tg ccccaacctt cccaactcag ggcaggaaga ctatgacaag 2340 gatggaatcg gcgatgcctg cgatgatgac gatgacaatg ataagactcc a gatga cagg 2400 gacaactgc c cattccatta caacccagcc cagtacgact acgacagaga tgacgtggga 2460 gaccgct cty acaactgccc ctacaaccac aacccagacc aggctgacac agataacaat 2520 ggggiaggag acgcccgtgc agctgacatt gatggggaca gt atcctcaa tgaacgggac 25S0 «Actgecagt atgtctacaa tgcggaccag aaagacattg a cacg? Acgg ggc tggtqat 2640 cagtgr.goca actgccccct ggaacacaat ceagaccagc t cgactctga ctcggaccgc 2700 atr q.jagaca cctqtgaca a caa l ca qat actgacgaa? ? Acggccacca gaacaatctg 2760 g = caactgtc cctacgtgcc caacgccaae caggctgacc atqacaaggc tggcaaaggp 2820 at gcctgtg acoatgacga cgaca ^ tcat ggcattcctg at gaccggga caactgcagg 2880 atcctgacca ctggtgccca gatggtgatg gaaggactct tgcttgcaaa gtcgaggtga 2940 gat gat - t tg accaggacaa ggtgccagac actgatgaca tctgtcccga aaatgttgat 3000 atcagt gaga ctgatttccg ccgattccaq ATGATT cctc tagatccc = to egggacatcc 3060 cagaatgacc ctaaccgggt tgtacgccac cagggtaaag aactcgtcca gactcccaac 3120 tctgaccctg gacttgctgt AGGT t atgac gaattraacg ctgtggactt cagtggcace 3180 ttcttcatca acaccgagag ggatgacgac tatgccggct ttgtgtctgg ctaccagtcc 324 G agcagocgct tctatgttgt gatgtggaag caagtcactc agtcecactg ggacaccaac 3300 cccacgaggg ctcaggggta ctctggactt tccgtgaagg ttgtaaactc eaccacgggg 3360 cctggcgagc acctgcggaa tgccctgtgg cacacaggaa acacctctgg ccaggtgcgc 3420 acactgtggc atgaccctcg tcacattggc tggaaagatt tcactgccta cagatggcat 3480 ctgagccaca ggccaaagac aggtttcatc agagtggtaa tgtatgaagg gaagaaaatc 3540 atggctgacc caggacccat ctatgacaaa accta tgctg gtgggaggct aggcttgttc 3600 gtcttctctc aagaaatggt gttcttctcc gacctgaaat atgaatgcag agactcctaa 3660 tcatcaaact gttgatcaaa agactgatca taaaccaatg ctggtaccgc accttctgga 3720"ccatgggct tagaaaaccc ccaggatcgc gcctcgctgc ctgcctttgc tctctgcttg 3780 gacccctaga catgagcglg cgcctcaaga acacgtgact ttccaaatca aaatgcaact 3840 gaccctgcat tcagcctctg actgagaaga atcttccaag gagacaaaca atgactttgg 3900 ttggcttttg agcatccaca caaaagcaaa tgctctggtt ggaaggtgcc tgtcccaccc 3960 tgcctttgtc agagcagaat gcgactgtga ggccagctct gagcagtgga ctccaaaatg 4020 tgtgagagaa ttttcaggca gggaggactc actagaattg acaaacaaaa ccagccctga 4080 cctacccccc ctggaatggg ggcgggtggg ggggccaaag cccaaagggg aggatgcata 4140 cccaagagac STAP tatga agaaaatatg gaggaactgt tacattcccg gcactaaatc 4200 atctccaggg gattgaaaga ctattgccgg atttcatgat gctgaccggt gttagctgat 4260 taacccacac aaaCaggcac ttaaaLagga gcaggqaagg aaggaassga ctggcctccg 4320 cacatttcca gacctcctoc ccccttaaca catcacctgt agtgaccaga acagggagtc 4380 gcagttaasc c? acacaagg cagggccagc tgctgcagct tqqtcctstt gaaactqtca 4440 gttctattcc agatgcagct tctgcagatg tagcagcaaa ataaqaatac ccaccacctc 4500 agcgagcacc aegetgtctc c agggacg gcagccatgc ttgtattttt atgqttagaa 4560 ttatcaacta asgcacaaaa agacattcct tctttctctt tttttcctga acatcatgga 4620 gtttcccagt tgtctctttc gcacr.gtagt ttttagtgtt ttaaacaaac actttacaac 4680 gtaaactatt tattttttac ttattctggg ggatctgtct gaaagactat tcatggaaca 4740 gqaagaagcg taaggactat ccatatcatc tttgctacaa gtcactacga ctgcaagatt 4800 gtaaacacag atcatttact 'aactctgtcc tacctgqaac ctagtctcsc atggaaagtg 4361 ttcgagagca ggtagttgag atcgatcagc aaatctttca caggaatggc acaaggaaac 4920 cagcatagca agctgctctt caccttgtgc ttagactgga tgatttgsaa ttctcctctc 4980 cttttttttc ccaagtggaa ttacttggtt gtccatttgc aagtgttttt agtttgcaaa 5040 gaaagccaag aggccattaa tactgtctta tcccatccct tgtgcctatt tccagggaga 5100 tgaaaagcat ctacatttat tatttttgcc tttttccaaa agaaaaaaat gacaaaggtg 5160 aaacttgtat acaaatatta cc catctgt gtgtgactg agtaaagaat tttgggatca 5220 aacagaaaga gtttaagtgt ctaacaaact taaagct act gtagtaccta aaaaaaaaaa 5280 ßaaaaaaaa 52S9 < 210 > 63 < 21i > 2053 < 212 > DNA < 213 > Unknown < 220 > < 223 > Description of the Unknown Body: Unknown < 4 ¡J0 > 63 gaattccggc ggccgctgag agcccaccct ggcgagctct cccagccgca gcctcccaat 60 ccacggcctc caccccgcgc ctctccagcg ctccatcccg tcgctgcgcc cttgtcgccg 120 gccccggcgc tgcatccgcg tccgcacagg ctccttgact gggcacaaat agctccacca 180 tgggqctggc ctgg gactc ggtgccctgc tcccgttgca tgcctgcggc tccaaccgca 240 ttccagagtc tgggggagac aacagtgcgt ttgacatctt tgaactcacc ggagctgccc 300 gcaacggcac tgggcgecga ctggtgaagg gccctgaccc ttctagccca gctttccgca 360 tcgaggatgc caacctgatc ccccctgtgc ctgacaagaa gttccaagac ctagtggatg 420 ctgtgcgggc ggagaaaggt ttcctcctcc tggcctcccc gaggcaaatg aagaagaece 480 ggggtacece gctggctgtg ga? cggaaag accactctgg ccaggccctc agcgtgatct 540 ccaatggcaa ggcgggcacc ctggacctga gcctgaccgt gcaggggaag cagcatctgg 600 tgpcgg gga agaageaetc ctggcgaceg gccagtggaa gagcat CACC ctgtttgtgc 660 aggaggacag ggcccagctg tacategact gtgagaagat gga.gaatgcg gagetegatg 720 gageatette tccccatcca accagggaec tggccagcat cgccaggctc cgcatrgcca "60 aaggaggtgc caaegacaat ttccaggggg tcctscagaa cgCaaggccc gtcttcggaa 84C ccacaccaga agacatcctc aggaacaaag gctgctccag ctctaccagt gcccttgtca 900 cccccgacaa caacgtggtg aatgggtcca gccctgccat ccgcaccgac tacatcggcc 960 ggacctgcaa acaagacaaa gccatctgtg gcatctcatg tgacgagccg tecagcatgg 1C20 tcctggagct caggggtcta cgcaccatcg tgaccacgct gcaggacagt atccgcaaag 1080 tgaccgaaga gaacaaagag ctggccaacg agctgaggag gcccccactc tgctaccaca 1140 acggagtgca gtacaggact ggcgacgagt ggacggtgga caqccgcacc gagtgtcgct 1200 gccagaactc agttaccatc tgcaaaaaag tgtcctgtcc catcatgccc tgctccaatq 1260 ccacagttcc ggatggagaa tgctgcccac g ? tgctggcc cagcgactct gcagacgacg 1320 gctggtcccc gtggtctgag tggacctctt gctetgtgac ctgtggcaat ggaatecago 1380 tcctgcgaca agctggccgc gcctcaacaa cagatgcgag ggctcctctg tgcagacgcg 1440 gacctgccac atccaggagt gtgacaagag atttaaacag gatggcgqct ggagceactg 1500 gtceceaCgg teatettget ccgtaacatg tggagacggt gtgatcacaa ggatccggct 1560 ctgcaactcc cccagccccc agatgaatgg gaagccatgt gagggcaaag cccgggagac 1620 caaagcctgc cagaaagact cctgccccat caatggaggc tggggaccct ggtcaccatg 1680 ggacatctgt tctgtcacct gcggagqagg ggtacagaaa cgtagccggc tctgcaacaa 1740 ceceacacee cagtttggag gcaaggactg cactggtgat qtqacacaaa accagatccg 1800 gactgtccca caacaageag ttgacggatg cctgtccaat ccctgctttg ceggtgtcca 186C gtgtaccagc taccetgatg gcagctggaa? tgtggtgcc tgtcccccag gctatagtgg 1920 agatggagtc gagtgcaaag acgttgatga gtgcaaagaa gtccctgatg cctgcttcaa 19S0 ccacaatgga gagcacaggt gtgagaacac agaccccggc tacaactget- tgccctgccc 204G accgcccgga att 2053 < 210 64 < 211 > 4339 212 > DNA < 213 > Unknown < 220 ^ < 222 > Description of the Unknown Body: Unknown < < 00 > 64 agccactgcc tggagtcagc cagcctcatc ggacttctgc aggcaatcgc gaagctgcta 60 tccagtcccg ccacggtctc tcccggcgca ccggcagtct cagcgtcccc accggactca 120 gcgtccttgt ccttcacttc acctttgcca cctctccggg ttactgaccc ccggtgcaca 180 caggctccgt gttgggcaca aaggctccac catggagccc ctgcggggac taggtgtcct 240 gttcctgttg catatgtgtg gaagcaaccg cattccagag tctgggggag ataacggtgt 300 tttgaactca gtctgacatc ttggaggtgc acgaaggggc cccggtcccc gactggtgaa 360 gggccaagat ctatccagcc ccgccttccg cattgagaat gccaacccga tccccgctgt 420 gecggatgac aagtcccaag acctactgga cgccgtgtgg gccgacasag gcctcatctt 480 cttgsc aka ttgaggcaga tgaagaagac ccggggcaca ctcctggctg tggaacggas 540 aqacaacact ggccagacct tcagtgtggt ctccaacggc aaagctggca ccctggacct 600 gagcctgagc ctgccaggga agcaacaagt ggtgtcagtg gaggaagccc tcctgqccac 660 tggccagtgg aagagcatca cgccgtttgt tcaagaggac cgggctcaac tctacataga 720 ctqtgataag atggagagcg cggagctgga tgtacccatc cagsgcstct tcaccaggga 780 tccggccagc gctgccaggc tccgagttgc aaagggagat gtcaatsaca attttcaggg 840 ggtgctgcag aatgtga ggt ttgtcttLgg aaccacccca gaagacattc tcaggaacaa 900 aggccgctcc agctctacoa acgtccttct tacccctgac aacaacgtgg tgaacggctc 960 atccgcacca cagccctgct actacatcgg ccacaaaaca aaggacctcc aagctatctg 1020 tgqccccccc cgtgatgaac tatccagcat ggtcctggaa ctgaagggcc tgcgcaccat 1080 ctgcoggaca cgtgaccact agtgacggaa gcatccgaaa gagaacagag agccggtcag 1140 tgagctgaag cggcctcccc tctgctttca cagtacaaga caatggagtc acaacgagga 1200 gacagttgca gtcqactgta cagagtgtca ccgccagaac tctgcaaaaa tcggttacca 1260 ggtgtcctgc cccatcatgc cccgctccaa cgccacastt cctgatggcg aacgctgccc 1320 acsgtgctgg cccagcgact ctgctgacca CGGC-tggrct ccctqgtctg agtggacctc 1380 acatgtggca ctgccccccc atggaattca gcaacgtggt cgttcccgcg acagcctcaa 1440 caacagatgc gagggctctt cggtacagac gaggacctgc cacattcacg agtstqacaa Iboo aagecttaaa gctggagtca caggacggcg ctggtctcca tggtcqtcct gttccgtgac 1560 ggtgtgatca ctgtggtgac caaggatccg tctctgcaac tcccccagce cccagatqaa 1620 cgtgaa cgggaagccc? GTG aagcccggga gaccaaagcc tgcaagaaag acgcctgccc 1680 aattaatgga ggctggggtc cc tggtcacc atgggacatc tgctctgtca cctgtggagg 1740 aggagtgcag agacgcagcc caaccccaca gactctgtaa ccccagtttg gaggcaaaga 1800 ctgtgttggc gatgtgacag aaaatcaagt ttgcaacaag caggactgcc caattgatgg 1S60 atgcctgtcc aatccctgct ttgctggcgc caagtgtact agctaccctg atggtagctg 1920 gaascgcggt gcgtgtcctc ctggctacag tggaaatggc atccagtcca aagacgtcga 1980 tgagtgcaaa gaagtgcctg atgcttgctt caatcacaac ggagaacatc ggtgcaagaa 2O40 cacagatcct ggctacaact gcctgccctg cccaccacga ttcactggct cacagccctt 2100 cggccgaggt gtcgaacatg ccatggccaa caaacaggtg tgcaaaccgc gaaacccctg 2160 cacggacggg acgeatgaet gcaacaagaa cgctaagtgc aactacctgg gtcactacag 2220 cg = ecccatg taccgctgtg agtgcaagcc ggcaatggca cggctalgca tcatctgcgg 2280 agaggacaca gacctggacg gctggcctaa tgaaaacctg gtgtgtgtgg ccaacgcaac 2340 aaaaaggaca ctaccactgc actgccccaa ccttcccaac ccqqgpcagg aagaccatga 2400 attggcgatg caaggacggg cctgcgatga tgacgatgac aacgacaaga tccctgatga 2460 cagggacaac tqcccattcc attscaaccc agcccagtac aactacg = ca gagatgatgt 2520 gggagaccgc tgtgacaact gcccccac aa ccacaaccct qaccaagcag aaacaqacaa 2580 aaacggggag gccgatgcct gtgccgtgga catcgatgga gacgqaaccc tcaacgaacq 2640 agaceactsc cagtacgttt acaacgtqga ccagagggac acggacacgg atggggttgg 2700 agatcagtgt gacaactgcc ccctggaaca caatccagac cagctggact ctgactcaga 2760 cctca AGGC gacacttgtg acaacaatca ggacatcgat gaggatggcc atcagaacaa 2820 cccggacaac cgtccctacg cgcctaacgc caaccaggcc gaccatgata aagatggcaa 2880 aggagatgc-c- tgtgaccat acgataacaa tgacggcatc cctqatgaca qagacaartg 2940 caggocggtg cccaatcctg accagaagga ctctgatggt gatggccgag gtgaegeocg 3000 caaacaogac tttgaccatg acaatgtgcc agatattgat gacatctsce ct aga3ttt 306u tgécaccagt gaaaccga c tccgacgatt ccagatgatt cccctagatr ccaaaggaac 3120 ctcccaaaat gaccctaact gggttgtccg ccatcagggc aaagaactcs tccagactgt 3180 aaactgtgac cctggacttg ctgtaggtta tgatgagttt aatgctgtgg acttcagcgg 3240 taccttctcc atcaacaccg agagagatga tgactacgct ggcttggtat tcggctacca 3300 gtccagcagc cgcttctacg ttgtgatgtg gaaacaagtc acccagtcct actgggacsc 3360 caaccccaca agsgctcagg gatactcagg aaggttgtga cctgtctgta actccaccac 3420 c? gccctggc gagcacctgc ggaatgcact gtggcacaca ggaaacaccc ctggccaggt 3480 gcscaccctg tggcatgacc ctcgccacat cggctggaaa gatttcactg cgtaeagatg 3540 gcgccC-acc cacaggccaa agaccggtta tatcagagtg gtgatgtatg aaggaaagaa 3600 = tcatggct gactcgggac ccatctatga caaaacctac gccggcggta sactaggcct 3660 tctca gctcgtcctc? GAAA tggtgttctt ctcagacatg aaatacgagt gtcgagattc 3720 ctaatcatca gctgccaatc ataaccagcg ctggcaatgc acctcctaaa aacaagggct 3780 agagaaaccc cccacccctg ccgggatcgc ctttcctcgc cttccttgcc tctcttcttg 3840 eatagcgcgg acttgtaaag cctgagacct gcctcaagaa aatgcagttt tcgaacccag 3900 agtccgcoct cgqcctctaa cgaatgagaa tqcaccttcc aagaccacga agagtccctx 3960 gggtttgctt ttgggaaagc caaagcgcct atttacttcc cactaggaag gtgcccgctc 4020 tactcacaga caccctgcct gccagaactt cttcgagqcc acctctgagc agctcacaca 4080 gaagcattcc caggcatgtc aaagaa agga aaaatgacte actagaactc accgccaaac 4140 aacctccgac ataggccctg agatgtgggg aggcaggagc caaagctcta gggagqqcat 4200 gtacccaaga gatgactgta tgaagaaaat gtggaggagc tgttcqtac taaatcattt 4260 tcaccggaca gacagacttg ctgcatttcc gcatgctgct ggtgagagct gattgaccca 4320 atcttccaca caggcactt 4339 < 210 > 65 < 211 > 186 < 212 > DNA < 212 > Unknown < 220 > < 223 > Description of the Unknown Body: Unknown < 400 > 65 gcacagtcaa tggaggctgg ggtccctggt caccatggga catctgctct gtcacctgtg 60 gaggaggagt gcagagacgc agccgactct gtaacaaccc cacaccccag tttggaggca 120 aagaccgtgt tggcgatgtg acagaaaatc aagtttgcaa caagcaggac tgcccaattg '. B d gtaagc 186 < 210 > 66 < 211 > 5774 < 212 > AD < 213 > Unknown < 220 > < 223 > Description of the Unknown Body: Unknown < 400 > 66 gtcactttgg ttgatagcag ccgctctggt agaggttagg acttcagctg atggacaaqe 60 tggtaatgaa gaaatggtgc aaatagattt accaataaag agatatagag agtatgagct 120 gtcagcacaa ggtgactcca atctagaagg acgctatctc tcccatactc tttctgcgag 180 tcacaaaaag aggtcagcga gggacgtgtc ttccaaccct gagcagttgt tctetaacat 240 cacggcattt ggaaaagar.t ttcacccgcg actaaagccc aacactcaac tactacctcc 300 cggggctgtt gtggagtggc atgagacatc tctggtgcct gggaatacaa cc? Atcccat 360 caaccaggaa taacaaccat gtgctacgta ._tagaatccgg aaaacagagc ctccgeagac 42C taaccqtgct tatgttggtg acatcgtgga cattccagga acctctgttg ccaccaccad 480 ctctgacggt ccggctggaa tgataaaaag tgataatgaa gagtatttca ttgaaccctt 540 ggaaagaggt aaacagatqg aggaagaaaa aggaaggatt catqttgtct acaasagatc COO agccgtagaa tagacacgte caggctccca caaagacccc cactacagag astcgcacct 660 ggaaggcctc gatgatccag gtactgttta tggcaacatc caccagcagc tgaatgaaac 720 aatgagacgc cgcagacacg cgggagaaaa cgactacaat atcgaggtac tgctqggaqc 78C ggacgactct gtggtccgtt tccacggcaa agagcacgtc caaaactacc ccetcaccct 840 aatgaacatt stgaa tgaaa tttaccatga tgagtccctc ggagcgcata taaatccggt 900 cetggtgcge atgataat? p tgggatatgc aaagtccatc agcctcatag aaaggggaaa 960 agcttggaga cccatccaga atgtgtgtcg ctgggcgtcc caacagcaaa gatctgatct 1020 caaccaetct gaacaccatg accatgcaat ttttttaacc aggcaagacc ttggacctgc 1080 tggaatgcaa ggatatgctc cagtcaccgg catgtgtcat ccagtgagaa gttgtaccct 1140 gaatcatgag gatggttttt catctgcttt tgtagtagcc catgaaacgg gccatgtgtt 1200 gggaatggag catgatggac aaggcaacag gtgtggtgat gagactgcta tgggaagtgt 1260 catggctccc ttggtacaag cagcattcca tcgttaccac tggtcccsat gcagtggtca 1320 agaactgaaa agatataccc attcctatga ctgtctcctt gatgacccct ttgatcatg = 1380 tcggcocaaa ctcccagaac ttcctggaat caattattct atggatgagc aatgtcgttt 1440 cgscttcggt gtcggccata aaatgtgcac cgcgttccga acctttgacc catgtaaaca 1500 gctgtggtgt agccatcctg ataatcccta cttttgtaag actaaaaagg gacctccact 1560 Lgacgggact gaatgtgctg ctggaaaatg gtgctataag tgtggaagaa ggtcattgca 1620 tgctastcag caaaaacaag atggcaattg ggggtcatgg actaaatccg gctcccgttc 1680 tcqgacatgt ggaactggtg tt cgtttcag aacacgccag tgcaataatc ccatgcccat 1740 caggattgtc caarggtggt ctggtgttaa ttttgagtac cagctttgta acacagaaga 1800 at? ccaaaaa cactttgagg acttcagagc acagcagtgt cagcagcgaa actcccactt 1860 tgaataccag aataccaaac accactggtt gccatatgaa catcctgacc ccaagaaaag 1920 acgccaccct tactqtcagt ccaaggagac tggagatgtt gcttacatga aacaactsgc 1980 acgcactgtc gcatgarqqa cttacaaaga tccatatagc atatgtgccc gaggagagtg 2040 tctgaaagtg ggctgtgate aagaaattgg ttctaataag gttgaggata agtgtggtgt 2100 ctgtgqagga gacaattccc actgccgaac cgtgaagggg acatttacca qsactcccag 2160 gaagcttggg taccttaaga tgtttgatat accccctggg gctagacatg tgttaaccca 2220 agaagacgag gcttctcctc atattcttgc tattaagaac caggctacag gccattatat 2280 tttaaatggc aaaggggagg aagccaagcc gcggaccttc atagatcttg gtgtggagtg 2340 ggattataac attgadgacg acactqaaag tcttcacacc gatggaccct tacatgatcc 2400 tgttattgtt ttgattatac ctcaagaaaa tgatacccgc catataacta cctagcctga 2460 catcacccat gaagactctg cacctacaat caacagcaac aacgcc = aka agg = agaatc 152C agatactttt gastgggctC tgaagagc tg gtctcaggtt tccaaacoct gtggtggagg 2580 tttccagtac actaaatatg gatgccgtag gaaaagtgat aataaaacgg cccatcgcag 2640 cttctgtgag gccaacaaaa agccgaaacc tattagacga atgtgcaata ttcaagagtg 2700 tacacatcca ctctgggtag cagaagaatg ggaacactgc accaaaaccc gtggaagttc 2760 tggctatcag cttcgcactg tacgctgcct tcagccactc cttgatggca ccaaccgccc 2820 aaa tgtgcacagc actgca tgggtgaccg tcccgagagc cgccggccct gtaacagast 2880 gccctgccct gcacagtgga aaacaggacc ctggagtgag tgttcagcga cctgcggtga 2940 aggaacggag gcgaggcagg tcctctgcag ggctggggac cactgtgitg gcgaaaagcc 3000 tgagtcggtc agagcctgtc aactgcctcc ttgtaatgat gaaccacgct tgggagacaa 3060 gtccatattc tg caaatgg aagtgttggc acgatactgc tccataccag gccacaacaa 3120 gttacgttgt gagtcctgca gcaagcgcag tagcaccctg ccaccaccat accttctaga 3180 agetgctgaa actcatgatg atgtcatctc taaccctagt gacctcccca gatctctagt 3240 gatgcccaca tctttggttc cttatcattc agagacccct gcaaagaaga tgtctttgag 3300 tagcatctct tcagtgggag gtccaaatqc atatgccgcc ttcaggccaa acagtaaacc 3360 tgatggtgct aatttacgcc agaggagtgc tcagcasgca ggaaqtaaga ccgtgagact 3420 ggtcaccgta ccatcctccc cacccaccaa gagggtccac ctcagttcag cctcacaaat 3480 ggctgctgcc tcctcctttg cagccagtga ttcaataggt gcttcctctc aggcaagaac 3540 gatggaaaga ctcaaagaaa tcattgacaa cagacgcccg acaagacoac ccacctcaga 3600 agtgaaccaa aagatgagaa aaaggctaga aaccagagga aaacctggac aacctctctc 3660 ttcccacggt gcatatgctt gtttaaagtg gaaatcccca tagatcgcca gcccattcta 3720 gaagaacaga tctgtaattg aagtgctggc tcactttcta gttqctctca tcctcc tttt 3780 gttccgcatt gactcattta ccagaat ttggaagaaa ca ttattacaaa tcaccaasga 3840 agaaaaatat gttgctaaga ttgtgttggt cgctccctga agcagaaasg ggactggaac 3900 tatcagctga caatcgtgca ctttctgttt gttttagaaa agttacagta aaaattaaaa 3960 acggttcaca agsgacacca ccttaacaag aaattttgg = cacggaacaa agaactccta 4020 gacttgtatt cctatttatc catattagaa atattgtatg agcaaatccg cagctq-rgt 4080 gtaaatactg tatattgcaa aaatcagtat tattttaaga gatgtgttct caaacqatcg 4140 tttactatat tacatttctg gatgttctag gtgcctgtcg ttgagcattg ccttgtttga 4200 cattctatag gttaattttc aaagcagagt attacaaaag attacagcta agaagttaga 4260 ctgacaatat aaagggtttt gttgaatcaa caatgtgata cgtaaattat agaaaaagaa 4320 aagaaacaca aaagctatag atatacagat atcagcttac ctattgcctt ctatacttat 4380 aatttaaagg actggtgtct tagtacactt gtggtcacag atagtaaata ggatcaacga 4440 atcaactcgt gcaagacaaa aetgaaaccc tctttccagg acctcagtag gcaccgttga 4500? gcgtccttt gtttttgtgt gtgtgtgttc ttttttaatt ttcgcattgt cgacagacao 4560 aaacagj at actcaacgta ctgtaataat cgcaaaggaa aaagttctsg gacaactcar 462c ttgtatgttg gtagctgaga aaaatatcat cagtctagaa ttgatatttg agtatagtag 4680 agctcc GGG ccttgaaggc aggttcaaga aagcatatgt cgacggttga gatatttatc 4740 cccatgttca ttccatatgg aatgttcaca accacaatgc atctgactgc aataatgcgc 4800 taataattta tgtcagtagc caccttgctc acagcaaagc cagaaatgcc ctctccaggg 4860 aagtacttgt agcagatgta acatagaatt cagaactgaa gatatctatt aaaagtcgar 4920 ttttttttct tgatagtett tttatgtact aaatatttac sctaatatca attacatatr 4980 ttggtaaact agagasacat aattagagat gcatgctttg ttctgtgcat agagaccttt 5040 aagoaaacta ctacagccaa ctcaaaagct aaaactgaac aaatttgatg ttatgcaaac 510C atcttgcatt tttagtagtt gatattaagt tgatgacttg tttcccttca to? gaaacatt 5160 aaactgtatg gactcagcta gctgctcaat attagaaaca gaaattgtga tttttaaaag 5220 tttttgaaag agataagtgc atcatgaatt acatgtecat gagaggagat agtgatatca 5280 gcacaacgat tctgaggtca gtacctgagc tgtctaaaaa tatattatac aaactaaaat 5340 taacctctca gtagatgaat tgtgcaagaa aagcacagaa ctttcgcatt ttaaCcgttg 5400 gcttaaacta taaectaaca ttgactctat acctctaaag aattgctgct actttgtgca 5460 a qaaocttqa aggtcaaatt aggcaaattc cagacagtaa aacaacccct aagccttaag 552c toctrctttc rtcctaaaaa ctcccataga ataaaattct ctctagccca cttgc ^ glg 5580 catacatctc atccacaggg gaagataaag atggtcacac aaacactttc Cataa = gatg 5640 tacatattea ttacacttct gacctccggg ctttctttte taetaagcta aaaattcctt 5"O0 tttatcaaag tgtacactac tgatgctgtt tgttgtactg agagcaccta ccaataaaaa 5760 5774 tgttaacaaa atat < 210 > 67 < 211 > 5535 212 > DNA <; 213 > Unknown <; 220 > 223 Description of the Unknown Body: Unknown < 40C > 67 ggactttaga agccgttgct gccctctctg tcacctgaag cggggccctc tcccatccca 60 cccttgcccc gcctccctgc ccccaccggg ccggccctqc ccgccgccgg accccggcat 120 gtcaagacct ggtccgcgcc tgcctgccca gcccgcggaa ccccggcggc cccgcgagct 180 aggatgaggg gccaggccgc cgccccgggc cccgcctgga tccccgcccc gctgctactg 240 etgctgctgc tgctgggacg ccgcgcgcgg gcggccgccg gagcagacgc ggggcccggg 300 cccgacccgt gcgccacgct ggtgeaggga aagttcttcg gctacttctc cgcggccgcc 360 gtgttcccgg ccaacgcctc gcgctgctcc tgqacgctac gcaaccc g cccgcggcgc 42C tacactctct acatgaaggt ggccaaggcg cccgtgccct gcagcggccc cggccgcgtq 460 cgcacctacc agttcgactc cttcctcgag tccacgcgca cetacctggg cgtggagagc 540 ttcgacgagg tgctqcggct ctgcgaeccc tccgrracccc tggccttccr. ccagc GCAG 600 aagcagttce tgcagatgcg scgccagcag ccgccccaqc acqacgggct GGCC ^ CCCGG 660 gccgggccgc cgggccccac cgacgacttc tccgtgsagt acctggtgqt ggggaaccgc 720 aaccccagcc gcgccgcctg ccagatgctg tgecgctggc tgqacqcgtg tctggccggt 780 agtcgcagct cgcacccctg cgggatcatg cagaccccct gcgcctgcct gggcggcgag 840 gcgggcggcc ctgccgcggg acccctggcc ccccgcgggg atgtctgctt gagagatgcg 900 gtggctggtg gccctgaaaa ctgccccacc aqccrgac c aggaccc.-pq cgggeacggc 960 gccaoaggcg gctggaagct gtggtccctg tggggcgaat gcacgcggga ctgcggggga 1C20 ggcctccaga cgcggacgcg cacctgcctg cccgcgccgg gcgtggaggs cggcggctgr 1080 gasggggtge tggaggaggg tcgccagtgc aaccgcgagg cctgcggccc cgctgggcgc 1140 accagctccc? gagccagtc cctgcggtcc acagatgccc ggcggcgcga ggagctgggg 1200 gacgagctgc agcagtttgg gttcccagcc ccccagaccg gtgacccags agccgaggag 1260 tcgtccccgt ggagcgtgtg ctccagcacc tgcggcgagg gctggcagac ccgcacgcgc 1320 ttctgcgtgt cctcctccta cagcacgcag tgcagcggac ccctgcgcga gcagcggctg 13B0 tgcaacaact ctgccgtgtg cccagtgcat ggtgcctggg atgagtggtc gccctggagc 1 440 ctctgctcca gcacctgtgg ccgtggcttt cgggatcgca cgcgcacctg caggcccccc 1500 cagtttgggg gcaacccctg tgagsgcccc gagaagcaaa ccaasctccg caacattgcc 1560 ctgtgccctg gccgggcagt ggatggaaac tggaatgagt ggtcgagecg gagcgcctgc 1620 tccgccagct gctcc.-AGGG ccgacagcag cgcacgcgtg aatgcaacgg gccttcctac 1680 gggcgtgcgg agtgccaggg ccactgggcg gagacccgag actgcttcct gcagcagtgc 1740 ccagtggatg gcaagtggca ggcctgggcg tcatggggca gttgcagcgt cacgtgtggg 1800 gctggcagcc agcgacggga gcgtgtctgc tctgggccct tcttcggggg agcagcctgc 1860 aggatgagca cagggccccc ccggcagtgc ggcacccagc ggtgtcccga gcccca gag 1920 atctgtgatg aggacaactt tggtgctgtg atctggaagg agaccccagc gggagaggtg 1980 gctgccgccc ggtgtccccg caacgccaca ggactcatcc tgcgacggtg tgagctggac 2040 gaggaaggca tcgcctactg ggagcccccc acctacatcc gctgtgtttc cattgactac 2100 gacaeatce agatgatgac ccgggagcac ctggccaagg ctcagcgagg gctgcctggq 2160 gagggggtct cggaggtcat ccagacoctg gtggagatct ctcaggacgg gaccagctac 2220 agtggggacc tgctgtccac catcgatgtc ctgaggaaca tgacasaqat tttccggaga 2280 qc ctactaca gccccacccc tggggacgta cagaactttg tccagatcct tagcaacctg 2340 ttcgcagagg aqaatcggga caagcgggag gaggcccagc tggcgggccc caacgccaag 2400 gacctgfctcc ggctggtgga ggactttgtg gacgtcatcg gcttccgcat gaaggacctg 2460 aqqaatgcat accaggtgac agacaacccg gtcctcagca tccataagct cccagccac.? 2520 ggagccactg acatcagctt ccctatgaag ggctggcggg ccacgs tga ctgggccaag 2580 ccgccagagc acagggtcac tgtgtccaag agtgtctt ct ccacggggct gacacaggcc 2640 gatgsagcat ccgtgtt tgt ggcgggcacc gtgctccaca ggaacctggg cagcttcctg 2700 gccctgcaga ggaacacgac cgtcctgaat tctaaggtga tctccgcgac tgtgaaaccc 2760 ccgcctcgct ccctgcgcac acccttggag atcgagttcg cccacatgta taatggcacc 2820 accaaccaga cctgtatcct gtgggatgag acggatgtac cctcctcctc cgcccccccg 2880 cagctcgggc cctggtcgtg gcgcggctgc cgcacggtgc ccctcgacgc cctccggacg 2940 cgctgcctct gtgaccggct ctccaccttc gccatctcag cccagctcag cgccgacgcg 3000 aacatggaga aggcgactct gccgtcggtg acgctcatcg tgggctgcgg cgtgtcctct ctcaccct 3060 gc tcatgctggt catcatctac gtgtccgtgt ggaggtacat tcgctcagag 3120 tcctcatcaa ccttctgtca cttctgcctg tccatcatet cetccaa.cgc cctcatcctc 3180 atcgggcaga cccagacccg caacaaggtg atgtgcacgc tggtggccgc cttcctgcac 3240 t tcttcccec CgCccCcctt ctgccgggcg cccaccgagg cctggcagtc ccacatggcc 3300 gtgacgggcc acctccggaa ccgcctcatc cgcaagcgct tectctsoct gggctggggg 3360 cccccCgcac cggttgtggc catttctgtg ggattcacc = aggccaaagg gtacagcacc 3420 atgaactact gctggctct c eetggagggg ggactgetct atgcctt cgt gggacctgcc 3480 cctgccgttg tgctggtgaa catggt att gggatcctgg tgt tcaacdd gctcqtgtcc 3540 asagacggca t cacggacaa? aagctqaag gagcgggcag gggcctccct gtggagctcc 3600 tccqtggtgc cgccgctgct ggcgctgacc tggatgtcgg ctgtgcccgc cgtcaccgac 3660 cgccgctceg ccctct tcca gatcctct tc gctgtcttcg act cgcc gga gggcttcgtc 3720 ec cgtcat gg t gcactgtac cc ccgtaga gaqgtccagg acgetgcg & To 3780 atgccgtgtg cttgaccggc aggaggaggg caacggygac tcagggggtt ccttccagaa cggctacgcc ccgacttcga 3840 cagctcatga gaaggacgt.g gatctggcct gtagatcagt gctgaacaag 3900 gacatcgcgg cctgccgcac tgccaccatc acgggcacac tgaagcggcc gtctccgccc 3960 ggaggaga ga agctsaagct ggcccatgcc aaggggccgc ccaccaattt caacagcctg 4020 ccqqccaacq TQT ccaagct gcacctgcac ggctcacccc gctatcecgg cgggcccctg 4080 cccgacttcc ccaaccactc actgaccctc aagagggaca aggcgcccaa gccctccccc 4140 gtcggtgacg gggacatctt * caagaagctg gactcggagc pgacecggge ccaggag3ag 4200 gctctggaca cgagctacgt gatcccgccc acggccacgg ccacgcCgog gcecaagccc 4260 aaggaggagc ccaagtacag catccacatt gaccagatgc cgcagacccg cctcatccac 4320 ctcagcacgg cccccgaggc cagcctcccc gcccgcagcc cgccctcccg ccagcccccc 4380 agcggcgggc cccccgaggc accccctgcc cagcccccac cgcctccgcc cccaccgcca 4440 ccacctcccc agcagcccct gcccccaccg cccaatctgg agccggcacc ccccagcctg 4500 ggggatcccg gggagcctgc cgcceatccg ggasccagca cggggcccag caccaagaac 4560 gagaatgtcg ccaccttgtc tgtgagctcc ctggagcggc ggaagtcgcg gtatgcaqaa 4620 ctggactttg agaagatcat gcacacccgg aagcggcacc aagacatgtt ccaggacctg 4680 aaccggaagc cgcagcacgc agcggagaag gacaaggagg tgctggggcc ggacagcaag 4740 ccggaaaagc agsagacgcc caacaagagg ccctgggaga gcctccggaa agcccacggg 4800 acgcccacgt gggcgaagaa ggagctggag ccgctgcagc cgtcgccgcc ggagct CGC 4860 agcgtggagt gggagaggtc gggcgccacg atcccgctgg tgggccagga catcßtcgac 4920 ctccagaccg aggtctgagc gggtgggcgg cggccacgca ctgggccac? gaggagggat 4980 gctgctccgc ccgctcctgc cgcagacggg cacagaeacg ctcgcgggca gcgggccagg 5040 cccgcacccc ggccccaggg cgcCcagacg gcggccaggc acagggcccg cagtgctggg 5100 accagagcca gatgcaggac aggaggcggc ccggccagcg ggcacagggc accagaggcc 5160 gaaggtgcct cagactccgc cctcctcggg ccgaggccea gcgggcagat gggcggacgg 5220 ctgtggaccg tggacaggcc cagcscggcc agccccccag ggtacccgcc tgagctcctq 5280 ctgcggagga gctgcctgct tggcccggcc ggcctggcac cgttttttaa acacccccat 5340 ccctcgggaa gcagccagct ccccacacct tccagggccc taggcccctc ctagacccag 5400 gtggacggca cagccccccg accctcatgg cccccagggg caggactgag tcccctccag 5460 gaagaagcag gggggaatct attttttctc tccttttctt ttcttcaata aaaagaatta 5520 aaaacccaaa aaaaa 5535 < 21 C > 6B < 21 i > 398 < 212 > DNA < 213 > Unknown < 22C > < 223 > Description of the Unknown Body: Unknown < 4C0 > 68 cggggcaacc cgctggagtg gacgggccag gtgacggtgc gcaagaagcg caagccctac 60 tceaagttcc agacgctcga gctcgagaag gagttcctct tcaacgcgta cgtcagcaag 120 cagaagcgct gggagctggc gcgcaacctc aacctcaccg agcgccaggt caagatccgg 180 ttccagaacc ggcgcatgaa gaacaagaag aacagccagc gccaggcggc cagcagcagc 240 agcagcaaca gcagcagcag cagcagcagc aacagcagca agcggccgcc ggcggggcgt 300 cggccgccgc caacggccac cagggccacc aagcgcacca ccacgcgccc cccaacggcg 360 ccgtcgcagc cctcaagcac caccagtgac ccgtagcg 398 210 > 69 < 21i > 8670 < 212 > DNA < 213 > Unknown < 220 > < 223 > Description of the Unknown Body: Unknown < 400 > 69 cccgggtgcg gtgtcgtgtg tggggctggg cgccacgt tc ctggacatgc tgagggccaa 60 gcgcgacacg gcgcccgacc gccgccagct ggacgaccgg atgatggggg cggacccggg 120 ggacatagcg gccaaggtga gggcagggt t ttgcstgcgt gct tgatt gt gcgtqtgcgt 180 gcgtgcgtce gtgcgtgcgq t gtt gcgtgt Gtat ttgaac cgt gt cttgt gtacgtacct 240 üggggtaaga gtgcatacac ATGCAT gcga ccggtggcct tacaaatcaa caacacgtac 300 gcccgcatgt at ccaggtgg cagcgtggcg acgagcacgt ggcttcgagg gcccaggcac 360 gccgggcccc agcggcagcg ccgccagt gg cagcggcgcc agcggccccg caccgc? GGC 420 gcgctcgccc .cgacctcagc caccgcggcc gcgctcacct tcacgcgggt gaaccccggc CCGT 480 gsggagccgc? tacgc gtqcgagcaa acaggtgcqt aagcgacgc tgggcagcgc 540 g gggggcgaga saagaggcgt gageaaaggg actagggaaa cgcacagcc = aatacggt at 600 gcgggcaacg aggcgatggc cctggaaacc gcagggccct ctcgaaatcg tgtaaggcgc 660 aattgctggg cgactaccgt agtctactga tgcattgcac tacttstatt actgtaccet 20 accgcagcag tgccgttgcc agccgcgctg ctgccctttg gctccccccc caacccaaat 78C ggcccatgcc tcgcgcactc cgagcaccca gagcacccag aagccgttgc gtgcgctccg 840 ccg ccgccct ctcccccgcc ttcacttctt aattaatcgt gaatgtaatc cccccccccc 900 ccgcttcctc aggctgggcg cacgtgtgcg cgacgcctgc acggagggcg tggcggatgc 960 ccgcagcgaa ctgctggtgt gcccggtgag tcgacgagga ggaggtgcaa gggggatacc 1020 agcgcgtgtt tctcagggcc tgtgtgggac accgaaacgt ggtaaaagag acccgcccgc 1080 gaaccgcgca tgtggagtag cgtggcgtgt gcggccggac cgacaaggca ccttgtggac 1140 tgccccacgt tgcagagtca gctgacaacg acacgtgcgc cttcctgtca ttgcccgtgc 1200 gcacgcacgc cccccgcact cccaacaaat tgacagcgac acgtgcgcct tcctataagc 1260 ccacqcccgc acacgctccc gcgccctcag gtgtcgggcc agaccacaga ccggttggtc 1320 cacgagtgcg aggaggatga ggcgggcggc tgcggcggcg ccggcggggc gccgcggcga 1380 ggaggacggc ctgggactgg gcatcacagg tgggtggcag gctggcaggg actcacgcat 1440 gggccttgta cgtgactgcg gttctgcatg gctagtggct cacgcgctgc gcacgttcae 1500 gtacggcttg tgggcatgca gtgccttgac gtgaggctgc gctgccctgc cgctgccgcc 1560 ttgccccgct cectgcacac actgca? ccg gcctcgggcg ccacttcacc gcgggctacg 1620 agcgcgagaa egcgcagcag ctcaacaggc tgctggggta caaggcgctg tgagagcgcg 1680 ccgoaggggg agtgtgttca tattgtggtt gcttgggccg tgggcgcggg ctgcatgtgc 1740 gcatcgcacg cgtacagcat tggtgaccgg tcaqgtgtaa gcggccggca gtgcgccgcg 1800 aggcgetgca gcgagttgtg gggcatgcgt catqcgeaga cggcccctgg acgacaaggc 1860 gttgagttgg cgtttggagg tgtgggacga cgtggggttt gtgccgtcaa agcacegaac 1920 to aaggcgtg accgtcttac gagctcgtat gatgtagcat ggattgaata atgacatgtg 1980 caagcgacga atttttgtta atgcgtgggg ttttggatgg caggsqtttc agtcgcccga 2040 ctgcgcatgc acacgtgacc aaatttatgc tcaacgacgt gaccattgct ttstacatac 2100 ctqtctatcg gttggcactt ataacaat cg gctcgtcaa? ttgacgcgag gctgcacttc 2160 gatcctgaaa gccccagttc aacaagtcgg atagccaaat ggccccgctc gctctccagc 2220 accaaggggc ctctaagt? c ctcgcggcaa gtgegctcccr cccagcgcaa gccgcggtga 228C gctggactcg tgcacttgcc gacgccgtcg gcaccgcaat cgaaagacgc gtgcgtcgag 234C caattgtgga agccgctgac gaattgtccg catgtgacat tgcaggctcg cgtccccgct 2400 cgtctcagcg tcatggccca ggtgcggacg ttgggactgc acttgcacga atgtgatggg 2460 gccgcaccga gtctgcgcgg acgtctcgct gacgtttcgc tctcgcaata gttgaatgca 2520 ggcagctgcc gcgccCgctg acaacactaa gaagctgtgg ggcggtcgct tcacgggcaa 2580 ctcatggaga gacggacccg agttcaacga gtcgctgccc tttqacaagc gcctgtgggc 2640 tgaggacatc aaggtgcggc acagggaggg gggcgagtgg tggggtgggg ctggggggga 2700 cgcgggtttg gtggccaggg cagggaggga agacgtgcgg ggctaggcaa gaggctgcga 2760 gggcccaggg taacaccaga ccgtgccgtg tcgcgtgccc ggcttgctgc ceecctcgcc 2820 caccgccctc cggccatccc atgacacgta cccaccagca cactccccca cacattcaca 2880 cacccacata cccacacacc cacgcattcc ccaacagggc agccaggcgt acgccaaggc 2940 tcttgccaag gccggcattc tggcacatga cgaggccgtg acca ttgtgg aggggctggc 3000 acacccggca caaggtgcgc gcagggcggg tgggtgggtg ggtggggtgg gggggcagag 3060 agaggcscgg gctgagaggg ggctgagagg ggggtcagcg aggcgcaggc tcagggggag 3120 gcgtctgagg ggggccgaga tggtggtggg ggagccgcgq gtgctsggcc tgctccggtg 3180 gcgggcgggc gggcgggcgg gcgacgtgta cgtgagtagc cgctgaccgg gcgccgggcc 3240 tttgcgcacg ccacagccca catgacaccg ccgcaaggcc cgccgcgccc cacccacgtt 3300 cacacactcc ccacacccac gcgtccgcgc gcctccttcc cctcaataca cgcgcctcct 3360 tcccotggcc cccgcctgct ccccccaccc ggccgccccg cctgcaggtg g cgaggagt 3420 ggaaggcggg tgcccttgtg atcaaggcgg gtgacgagga catccacacg gccaacgagc 3480 ggcgcctcac ggagctggtg ggggcggtgg gcgqcaagct gcacaccgec cgctcgcgca 3540 acgaccaggt gagggtgggt gggtgggggt ggggtgggtg ggtgggtggg tgggtgggtg 3600 ggtgggtggg tgggtgggtg ggtgggtggg ggtttgagat accggtacca ggecaaacta 3660 aaccgaaccc aagggggtgg cgtaggggcq tgggaggggg ggagtgcsga agccgcqagg 3720 c = ggagtaag ggcgggagga gggggccgga ggagaagcag ggaccaagcc gatgacaggc 3730 gcagtcg tg gcggcggtgg cgggtgcgcc gttgtgcagc ggccgtqai "accatgtgca 384:? qggcqgcg c ggggccgggc cgggggtggg agacctgtcc agaccccgtg gccctcttcc 390) agccccgtcc gccactgccg ccaccaccac cgccgccgcc gtagccacca cccctcacgt 3960 CGAG cactc cacagatgcg aagcaaccac accgttctcc acatgaacag ctaccctccc 4020 aaacccaact ttcccttccc gccttaccta accatgaccc gctacccccc cccccctcat 4080 ttcctaacca acca tgaatg cccccccccg gctgtacctg gctacgactt cacttcgtaa 4140 acttaatgtg tgtaaccccc cttacacaca cacacacacc cctccccgcC cctccaaagg 4200 tcgccaccga ctaccggctg tggctggtgg gtcaggtgga ggtgatgcgg tccgaggtgg 4260 gcgagctgat gcgcgtggcg gcggaccgct ccgaggcaga ggtggaggcg ctcatgccgg 4320 stgagyggg agggaggggg ggagggggag ggggaggtgc tcatgccggc gagggtaggg 4380 aggggaggcg cagaggaggg agggggagga gggggcggct gaggcaggga gagtgcggga 4440 tgagggcgat agaaagttgc gtattgccgg taaactcaaa ggactagacg aagagaacaa 4500 gggacctgga acccaaacaa gcgaggccaa atctgaacgt gacatcgccc gcctcctccc 4560 gctgcctgct cccccacctc ctcccccatc tcgccccccc ccccacacac acacaggctt 4620 cacqcacctt caqdatgcca tgactgtgeg ctggagccac tggctgatgá gccacgccgc 46B0 qccttgg aJ cqcgaccaoa tgcggctg g ggacctgctq ccgcggctgg ccacactgcc 4740 gctgsgcteg gqtgggtgag ggagggsagg ggaggggagg gggggagggg gagggagagg 4800 aggggagasg ggggggggag acgaggaggg tggaagggtg ggggcgggsc ggtggaggct 4860 agsgqgtggg gctgggtgcg cggacgga ^ t gcactggtag aggagggata gggtacattg 4920 agacgcgagg acggatgca g gggcgaaggt ggggaggagg ggaggg ^ acg aggcgtsgag 4980 ctgqagttígg ccgacgagtg tgcggacggg gcaggcggca acggggatta aacggcgggg 5040 ggcogggg g tgtgoacqac aggggctcgc gcgtctgcga ttgtgggggc acacagsgac 5100 aggagca ^ ga cgtgggacac gcatagatac gccgcattga caacacacac acacacacac 5160 acacacacac acacacacac acacacacaa acacaaacac acacaaacac aaacacacac 5220 acsccccccc ccctacacac acgccccctc cccaggcgcc ctggeeggoa acccctttct 5280 ggtcgaccgc cagtccaccg ccaaggagtt gggtttcggc ggcggcgtgc gccccaactc 5340 cacgcacgcg gigaggggag gaggaggggg aggagggcgg gggggggcag gaggggggag 5400 .gaggaggggg ggagggggct aactttgaag cgtaaggaaa cagtcgggag gaggggggga 5460 aggasggggc ctggaggagg gggggaggag gagggtggct ggagggggct gggggaggag 5520 gagggggagg attgggaggg ggccggggga gggtgcccgc agctggggga ggtggggagg 5580 gagggggttg ctgctggtgt aaagggcctg taggcactga gagcactgtg gggagccggg 5640 gtactgcctg gggccccgcg ctgcagaggt gtcgcgcagt gtggcggcgc atcccccgca 5700 tccccacaeg cgggccgctg ccgctgcccg ccacaccctt gccactctgc gtgctttcct 5760 agcataca cacacacaca cacacacaca cacacacaaa cacacacaca cacaaacaca 5820 cacgggcgcg ggctttcgtt tcgtttttta acacaaacac acactccccc tg gctcctc 5880 atctctctca aacacactcc cacgcacaca cacaaacaca cacatgcgca ggtgcccgac 5940 cgcgactttg tgatcgagac ggtgtttgcg gccagcctgc tgtgcgtgca cctgtcgcgc 6000 tggccggagg acctcatcat ctacagctcc ggccccttcg gctacgtgca gtgcagcgac 6060 gcctacgcca ccggctcctc gctcatgccg cagaagaaga accccgacgc cctggagctc 6120 atcaggtgcg ggagggatgg ggtgggggtg ggggggttac attcatggtt agttaagaag 6180 tgaaggegta gggggtggat ggggtgggtt acatttaaga acattcatga agtgaaggcg 6240 tasccaggaa C? gtagtaga gcagaegcgt tgtagtgtgt gggtttgggt ggsagggatg 6300 gttgggtaaa gcggtacagg atgtacrgag gactgcagac cgaaggagcg ggggaggggg 6360 agcaggcagg cggggcgagc ggcgcggggg cgggggttac tggcaccgtg ccgggtaagc 6420 aacacgtgac acggagatgc accaeacaaa gaggqacgtg gggagtggca ggcgggggcc 6480 agggctgaga ggcgcgcgtg gaggggtgcg gggttgggcg gggggctgtt tcatgatacc 6540 gctccctcca cetectccac cgcctcetgc cacctccacc tcccccaccg cccccccccg 6600 cctcctcctg ctgcaggggc aagggc ggtc gtgtgcagpg caacctgatq gscgtcatgg 6660 cggtgctcaa gggcacgccc accacataca acaaggactt ccaggcgaga gagcgagagc 6720 gggagagcga gagggaggga gggagaggga gggagaggga gacagaggga gggagaggga 6780 cagcg = CAGG gacagggaca gsgac.iggga ggcaggggca cagggacagg gggg ^ AGGGG 6840 cacgggcsgg ggcaggggag gccccccggg ggcggcgggc ccggggcatg aggtcagaca 6900 'taggggc? et gcactgagcc cgcgaggcgg gcgggaggca gggggcgggg ggcsgggggc 6960 atgcgccgca gggagcggac aacacagacg ggttgagaaa gcacaacgac tggaacgcag 7320 tgggettact gacaattcat cattgtgcgc atatgtgtgt atgtgtatgt gtgtgtttgt 7080 ttgtgcagga gtgttgggag ctgctgtttg acacggtgga cacggtgcac gacgtggtg.c 7140 gcatcgccac cggcgtgctg tccaccctgc ggatcaagcc cgaccgcatg aaggccggtg 7290 agcgtagccg agcagggctg gagcagcagc cgggcagcag tagcagcagg geaggggagc 7260 agcgggagcg ggagcagcag gaggggtggt tgggaagcgg tgggggtagg gtgggagcgg 7320 aggaagggaa ggaggagcag gagcaggagg aagaggagga ggaagggcgg tggggggtgg 7380 ggggtcgtgt ccttggccgc atgggcggag gcggggaggc ggggaggagg cggggaagca 7440 gagcctgcac ccacgctccg cgggtcccta cc gtcttgcg cctaaccccg tgcgcctagc 7500 ctcttgcgcc caccccctta gtgcatcctg tacccctctt tccaaacatc cttgcaactc 7560 cc gacctcc tcgccaaacc tcccccgccc ccaggcctgt ccgccgacat gctcgccacg 7620 gacctggccg agtacctggt gcgcaagggc gtgccgttcc gggagacaca ccaccacagg 7680 tgcgsccggg cgggagggcg tgagggcgtg ggtggggcat gcccggggtt gtgagagcta 7740 tcgaacgttg tgccgcgcct gtttcacaat gtcgggccac agggtacgca gtttcctct.c 7800 catatgtata acaaactgac caccaatcat gcasgeteac acgctctecc acacacacgc 7860 gcaccacgcc accacagcgg cgccgccgtg aagatggccg aggaccgcgg ctgcacgctg 7920 ccgtggacga ttceacctca cctcaagacc atccacccgc tcttcaccga cgacgtggcg 7980 gcggtgagcg gcggcccgga gcaqcagcag cagcagcagc agcagcagca gcagcagcag 8040 tagcctgggg gggagcgtqt gggaggaacg gcgggggagg ggaggcgggg ggtgtcgttt 8100 gcagccgagc gcacgtgstg ttccatgcca ctttgcccca gcagggtgac acacctgacc 8160 atgct? gtgt gctgctaggt ggttcacacc tacgtgtgaa tttgtgctgg cgtgcqcaca 8220 CCCC = ctgtg gccatgtgaa cggcatcctc atgtcctcgt gattgcgccc ggcacattgc S280 ccacsacccc gcaccaccca gctcctcaat ccagtgc aag qaaaqgaaat gcacacccac 8340 cgc? ccaaca acacgacgca tgtgtttgcc acgtgcgcgc acacacgcgc aggtgtggga 8 OC ctccaaocgc agcgccgaga tgcgcgacac ggagggcggc accagcaagc gctcggtget 8461? ggagcaggtg cagaagatgc gcacctacct ggcggcggag ggacagcacc gdgcge? GCT 352C ggggag ggg ggcgggtgtg tatgtgtgtg tgtgtgcgtg tgcaagcctc ggtggagggg 8580 cggccctcta tatggcggcg gggccacagg gggacgggtg tgacagagct acggccggag S640 S670 ccagcggagt cccgggatgg attaaggatc < 210 > 70 < 211 > 745 < 212 > DNA < 213 > Unknown < 220 > < 223 > Description of the Unknown Body: Unknown < 400 > 7C atgagatggc gacgcgcccc gcgccgctcc gggcgtcccg gcccccgggc ccaqcqcccc 60 ggccccgccg cccgctcgtc gccgccgctg ccgctgctgc cactactgct gctgccgggg 120 aecgcggccc tggcgccggg ggcggcggcc ggcaacgagg cggctcccgc gggggcctcg 180 gtgtgctact cgtccccgcc cagcgtggga tcggcgcagg agctagctca gcgcgccgcg 2 C gtggtgatcg agggaaaggc gcacccgcag cggcggcagc ag gsgcact cgacaggaag 300 gcggcsgcgg cggcgggcga gcaggggcg TGGG? Cggcg atcgcgagcc gccagccgcg 360 ggcccacggg cgctggggcc gcccgccgag gagccgctgc tcgccqccaa cgggsccgtg 420 cectcttggc ccaccgcccc ggtgcccagc gccsgcgagc ccggggagga ggccecctai 480 ctggtgaagg tgcaccaggt gtgggcggcg aaasccgggg gcttgaagaa ggacccqctg 540 ctcaccgcgc gccCggggac CTG? ggccae cccgecttcc cctccCgcgg gsggctcaag 600 saggacagca ggtacatctt cttcatqgag cccgacgcca acagcaceag ccqcgcgccg 660 gccgcccccc gagcctcttt cccccctccg gagacgggcc ggaacctcaa gaaggaggtc 745 720 ascegggcgc tgcgcaagcg gtgcg < 210 > 71 < 211 > 1986 < 212 > DNA < 213 > Unknown < 22C > < 223 > Description of the Unknown Body: Unknown < 400 > 71 gaaccccttt ttc tcttttt ttttttcttt ttttttttgc ccccataccc cct cgccc tc 60 ctgtggttcc atccacttct tccccctcct cctcccataa acaact CTCC tacccctgca 120 ataaataaaa cccccaataa ggaggagggs aaggggggag gaggaggagt ggcgctgcga 180 ggggaaggaa aagggaggca gcgcgagaag agccgggcag agtccgaacc gacagccaga 240 agcccgcacg cacctcgcac catgagatgg cgacgcgccc cgcgccgct c cgggcgtccc 300 ggcccccggg cccagcgccc cggctccgcc gcccgctcgt cgccgccgct gccgctgctg 360 ccactactgc TGCT gctggg gaccgcggcc ctggcgccgg gggcggcggc cggcaacgag 420 gcggct cccs cgggggcct c ggtgtgctac tcgtccccgc ccagcgtggg atcgstgcag 4 SC GAGCT TEAP agcgcgccgc ggtggtgat c gagggaaagg tgcacccgca gcggcggcag 540 cagggggcac tcgacaggaa ggcggcggcg gcggcgggcg aggcaggggc gcggggcggc 600 gategegage cgccagccgc gggcccacgg gcgct ggggc cgcccgccga ggagccgctg 660 ctcgccgcca acgggaccgt gcccccctgg cccaccgccc cggcgcccag cgccggcgag 720 cccggggagg aggcgcccca tctggtgaag gtgcaccagg tgtgggcggt gaaagccggg 780 ggcttgaaga aggactcgct gctcsccgtg cgcctgggga cetggggcca ccccqccttc 840 ccetc ccgcg ggaggctcaa ggaggacagc aggtacatct t ct tcatgga gcccgacgcc 900 aacaqcacca gccgcgcgcc ggccgcctcc cgagcctctt t cccccctct ggagacgggc 960 cggaacctca agaaggaggt cagccgggtg ctgtgcaagc ggtgcgcctc gcctccccaa 1020 ttg = tgaaaaqcca aasaga gcaggttcca ggaateggct aactaqt cct ccggt gtgsa 1080 accagttctg aatactcctc tctcaqactc aactggttca agaatgg aa tgaattsaat 1140 aaccacaaaa cgaaaaaaca tstcaagata caaaaaaagc cagggaastc agaaettege 1200 attaaeaaag catcactggc tgat tctgga gagtatatgt gcaaagtgat cagcaaatta 1260 ggaaatgaca gtgcctctgc caatatcacc ategtggaat caaacgct ac atctacatcc 1320 accactggga caagccatct tgraaaatgt gcggagaagg agaaaacttt ctgtgtcaaT 13S0 ggaggggagt gct tcatggt gaaaqacctt. Lcaaacccct cgaga u = ctt gtccdagtgr 1440 ttoctggtga ccaaatgagt tcgctgccaa aactacgtaa tggccagcct cc = cactaeg 1500 tccaccccct Ctctgtccct gcctgaatag gagcatgccc agttgscget gctttcctgt 1560 tgcCgcatct cccctcagat tccacctaga gctagatgtg tcttaccaga tctaatattg 1620 actgcctctg cctgtcgcat gagaacatta acaaaagcaa ttgtattact tcctctgttc 1680 gcgactagtt ggctctgaga tactaatagg tgtgtgaggc tccggatgtt tctgga ^ ttg 1740 atattgaatg atgtgataca aattgatagt caatatcaag cagtgaaata tgataataaa 1800 ggcattccaa agtctcactt ttattgataa aataaaaatc attctactga acagtccatc 1860 ttctttatac aatgaccaca tcctgaaaag ggtgttgcta agctgtaacc gatat? cact 1920 tgaaatgatg gtaagttaat tccgattcag aatgtgttat ttgtcacaaa taaacataat 1980 aaaagg 1986 21? ^ 72 < 2ll- > 2003 < 212 > DNA < 2i3 > Unknown < 220- < ?.?. 3 > Description of the Unknown Body: Unknown < 220 > < 221 IS NOT SECURE < 222 > (31) 2Z 3 J- It can be any nucleic acid < 220 > < 221 IS NOT SECURE < 222 (32) < 223 It can be any nucleic acid - "43C> 72 ggaattcctt tttttttttt CttttttcCL nnctcttttt tgcccttata cctcttcgcc 60 ttcctgtggt tccitccact tcttccccet cctcctccca t & Aacoactc tcctacccct 120 scacscccaa taaacaaaCa aaaggaggag ggcaaggggg gaggaggagg agtgctgctg 180 cgagggg ^ ag gaaaagggag gcagcgcgag aagagccggs cpgagtccga accgscaqcc 240 acaagcccgc acgcacctcg caccatgaga tggcgacgcg ccccgcgccg ctccsggcgc 300 cccgcceece gggcccagcg cc cqgetcc gccgcccgct cqtcgccqcc qccgceqctq 360 ctgccactac tgcccccgct ggggaccgcg gccccggcgc egggggcg: ggccggcaac 420 gaggcggccc ccgcgggggc ctcggtgtgc tactcgtccc cgcccagcrc gggaccagrg 480 caggagctag ctcagcgcge cgcggtggtg atcgagggaa aggtgcaccc ccagcggcqa 54C cagcaggggg cactcgacag gaaggcggcg gcggcggcgg gcgaggcagg ggcgtggggc 600 ggcgatcgcg agccgccagc cgcgggccca cgggcgctgg ggccgcccgc cgaggagccg 660 ctgctcgccg ccaacgggac cgtgccctct tggcccaccg ccocggtgcc cagcgccggc 720 gagcccgggg aggaggcgcc ctatctggtg aaggtgcacc aggtgtgggc ggtgaaagcc 780 gggggcttga agaaggactc gctgctcacc gtgcgcctgg ggacctggsg ccaccccgce 840 ttcccctcct gcgggaggct caaggaggac agcaggtaca tcttcttcat ggagcccgac 900 gccaacagca ccagccgcgc gccggccgcc ttccgagcct ctttcccccc tctggagacg 960 ggccggaacc tcaagaagga ggtcagccgg gtgctgtgca agcggtgcgc cttgcctccc 1020 caattgaaag agatgaaaag ccaggaatcg gctgcaggtt ccaaactagt ccttcggtgt 1080 gaaaccagtt ctgaatactc ctctctcaga ttcaagtggt tcaagaatgg gaatgaattg 1140 acaaaccaca aatcgaaaaa aaatatcaag acacaaaaaa agrcaggg ^ a gccagaaccc 1200 cgcattaaca aagcatcact ggctgattct ggaaagtata tgtgcaaacc gatcagcaaa 1260 ttaggaaar.g acagtgcctc tgccaatatc accatcgcgq aazcaaae and taeatctaca 1320 ggacaagcca tccaccactg tcttqtaaaa tgtgeggaqci aggauaaa = t tctctgtgtg 1380 aatggagggg agtgcttcat ggtgaaagac ctttcaaacc ccccgagacs cttgtgcaag 1440 tgcccaaatg agtttactgg tgatcgctqc caaaactacg taatggccai cttctacagt 150C acgcccaccc cccctccgtc tctgcctqaa taggaqcacg cccagttgct gctgctttct 1560 tcscccctca tgttgctgca gatr.ccacct agagctag ^ t. gtgtcttace agatctaaca 1620 ttgactgcct ctgcctgccg catgagaaca ctaacaaaag caatcgtacc acttcccctq 1680 ttcgcgacta gttggctctg egatactaat aggtgtgtga ggccccggat ctttccqgaa January 40 ctgatattga atgatgtgat acaaactgat agtcaacacc aagcagt? aa atacg = taat 1800 caaagtctca aaacgcattt cttttattga taaaataaaa atcattctac tgaacagtcc 1860 stcCcrttca tacaacgacc acaccctgaa aagggtgttg ccaagctgcs accgatatgc 1920 acccgaaacg atggtaagtt aattccgact cagaatgtgt catctgccac aaataaacat 298C aaaaaagga aaaaaaaaaa aaa 20C5 < 210 > 73 < 2il > 957 < 212 > DNA < 213 > Unknown < 22G > < 223 > Description of the Unknown Body: Unknown < 220 > < 22i > IT IS NOT INSURANCE < 222 > (809) < 223 > It can be any nucleic acid < 220 > < 22l > IT IS NOT INSURANCE < 222 > (810) < 223 > It can be any nucleic acid < 220 > < 221 > IT IS NOT INSURANCE < 222 > (821) < 223 > It can be any nucleic acid < 400 > 73 ccccgcccca acttcttccc ccgcgctccg cagcagcagc agcagcagca gcagcaqcag 60 ca = aatggca gaccccttca qcggactcgt gggcggcgtc gtcggcgclq ctgctgcagc 120 agatttgcct gcggagggcg agagggcccc ccgccccgcc cccggcactg cctggacttg 18C ctgctgcagc aaactgca? G aaggggcccg cgagctcgag scttttgtgc agcagctgag 240 ttttgttgca gggaagccgg cctqctgcct gcgggtgggg gcggagcagc tggcgcqctg 300 cgctgcggag gggcggctgc ccagcagcag cagcagcagc aqctgctgcg cgctgctgca 360 gctcgagaag caggacctcg agcaqagcct cgaggccggc aagcagggcg cggaqtgcct 420 cr.tgaggagc agcaaaccgc ccctegaggc cctcctcgag ggggcccgcq ttgcagcaac 480 gccgggtttg ctgctggtcq agagcagcaa agacacggtg ctgcgcagca ttccccacac 540 ccaggagaag ctggcccagg cctacegttc tttcctgcgg ggctaccagg gggcagcagc 600 cgggaggtet ctgggctacg gggcccctgc tgctgcttao ggccagoagc agcagcccag 660 cagctacggg gcgccccccg cctccagcca gcagccctcc ggctccccct ggtagccctg 720 cagcagcagc agcagcagcá gcagcagcag caqcgcgggc ggcacccscg gcggggccga 790 ggcgccgctg csgcaacagc agcagccgnn ncggctagcg ccgcggasca ctcgcaggga 84C actccacagg cagcg ggaga gcagcaggga cgagaagcag gtcatgtagc gcaggeagca 900 qcgccagctg cagcagcagc agcagcagca gcagcagcag cagcagctcc tgcaccg 957 < 210 > 74 < 211 > 957 < 212 > DNA < 213 > Unknown < 220 > < 223 > Description of the Unknown Body: Unknown < 220 > < 22I > IT IS NOT INSURANCE < 222 > (809) < 223 > It can be any nucleic acid < 220 > < 22l > IT IS NOT INSURANCE < 222 > Í810) < 223 It can be any nucleic acid < 220 > < 22i > IT IS NOT INSURANCE < 222 (811) < 223 > It can be any nucleic acid < 400 > 74 tcccgcccca acttcctccc ccgcgctccg cagcaqcagc agcagcagca gcagcagcag 60 gacctcttca caaaacggca gcggactcgt gggcggcgtc gtcg? Cgctg ttgctgcagc 120 agatttgcct gcggagggcg agagcgcccc ccgccccgcc cccggcactg cctggacttg 180 ctgctgcagc aaactgcaag aaggggcccg cgagctggag ggttttgtgc agcagccgag 240 ttctgttgca gggaagctgg cctgccgcct gcgggtgggg gcgqagca? C tggcgcgctg 300 cgccgcggag gggcggctgc ccagcagcag cagcagcagc agctgctgcg cgccgctgca 360 qctcgagaag caggacctcg agcagagcct cgaggccggq aagcagggcg cggagtgcct 420 etcgaggagc agcaaactgg ccctcgaggc cctcctcgag ggggcccgcg ttgcagcaac 480 gcggggtttq ctqctggtcg agagcagcaa agacacggtg ctgcgcagca ttccccacac 540 ccaggagaag ctggcccagg cccacagttc tetcetecgg ggctaccagg gggcaccagc 600 gggoaggtct ctgggctacg gggcccctgc tgctgcttac ggccagcagc agcagcccag 660 cagctacggg gcgccccccg cctccagcca gcagccctcc ggcttctccc ggtagccccg 720 agcagcagca cagcagcagc gcagcagcag cagcgcgggc ggcagccgcg gcggggccgg 780 ggcgccgctg cagcaacagc agcagccgnn ncggctagcg ccgcggagca ctcgcaggga 840 actccacagg cagcggg aga gcagcaggga cgagaagcag gtcacgtagc gcaggcagca 900 gcgccagctg cagcagcagc agcagcagca gcagcagcag cagcagctcc tgcaccg 957 < 210 > 75 < 211 > 1089 < 212 > DNA < 213 > Unknown < 220 > < 223 > Description of the Unknown Body: Unknown < 220 > < 221 > IT IS NOT INSURANCE < 222 > (376) < 223 > It can be any nucleic acid < 220 > < 22l > IT IS NOT INSURANCE < 222 > 1377) < 223 > It can be any nucleic acid < 220 > < 221 > IT IS NOT INSURANCE < 222 > (847) < 223 > It can be any nucleic acid < 22C > < 221 > IT IS NOT INSURANCE < 222 > (848) < 223 > It can be any nucleic acid < 220 > < 221? IT IS NOT INSURANCE < 222 > (849) < 223? It can be any nucleic acid < 220 > < 2 1 > IT IS NOT INSURANCE < 222 (850) < 223? It can be any nucleic acid < 4CC > 75 gaattccctc caactcttcg cgactccctc tctctcgccc caacttttte ccccgcgcce 60 cgcagcagca gcagcagcag cagcagcaaa atggcagacc tcttcagcgg actcgtggge 120 ggcgtcgtcg gcgctgttgc tgcagcagat ttgcctgcgg agggcgag = g ggccccccgc 180 cccgcccccg gcactgcctg gacttgctgc tgcagcaaac tgcaagaagg ggcccgcgag 240 ctggagggtt ttctgcagca gctgagtttt gttgcaggga agctggcctg etgcctgcgg 300 gtgggggcgg agcagctggc gcgctgcgct gcggaggggc ggctgcccag cagcagcagc 360 agcagcagct gctgcnngct? ctgcagctc gagaagcagg acctcgagca gagcctcgag 420 gccggcaagc agggcgcgga gtgcctcttg aggagcagca aactggcccc cgaggccctc 480 ctcgcggggg cccgcgttgc agcaacgcgg ggtttgctgc tggtcgagag cagcaaagac 540 acggtgctgc gcagcactcc ccacacccag gagaagctgg cccaggccta cagttctctc 600 ctgcggggct accagggggc agcagcgggg aggtctctgg gctacgggqc ccctgctgct 660 gct acggcc agcagcagca gcccagcagc tacggggcgc cccccgcctc cagccagcag 720 cccceeggct tcttctggta gccctgcagc agcagcagca gcagcagcag cagcagcagc 780 ggcggcggca gccgcggcgg ggccggggeg ccgctgcagc aacagcagca gccgcggcgg 840 ctagcgnnpn gagcactcgc agggaacCcc acaggcagcg ggagagcagc agggacgaga 900 agcaggccta tgtagcgcag gcagcagcgc cagctgcagc agcagcagca gcagcagcag 960 agctcctgca cagcagcagc ccgcagcccc gtgtcattta ttacgttggc agctctgagg 1020 cctcggcgca gccaacgcgc etcaqgtacc tttcaqactc ttttctct to ggtcttccag 1080 acggaattc 1089 < 210 > 76 < 21l > 1985 < 212 > AD < 213 > Unknown < 220 > < 223 > Description of the Unknown Body: Unknown < 400 > 76 cgccqagctt tL_.gqcacctc tgccgggtgg taccgagcct tcccggcgcc ccctcctctc 60 cccccaccgg cctgcccttc cccgcgggac catcgccccc acgtttccct cagccctttt 12C cccccccgsc cgagccgcgg cggcagcagc agcagcagca qcagcaggag gagsagcccg 1SC ctggcggcgg tggccgggga gcccatggcg tacagtcaag gagccggcaa aaaaaaagtc 24C tcctactact acgacggtga tattggaaat tattattatg gacagggtca tcccatgaag 300 cctcatagaa tccgcatgac ccataacttg ctgttaaatt atggcttaca cagaaaaatg 360 ggccccataa gaaatatata agccactgcc gaagaaatga caaaatatca cagtgatgag 420 tstatcaaat ttctacggtc aataagacca gataacatgt etgagtatag taagcagatg 480 catatattta atgttggaga agattgtcca gcgtttgatg gactctttga gttttgtcag 540 ctctcaactg gcggttcagt tgctggagct gtgaagttaa accgacaaca gactgatatg 600 gctgttaatt gggctggagg attacatcat gctaagaaat acgaagcatc aggattctgt 660 tecgccaacg acattgtgct tgccatcctt gaattactaa agtatcatca gagagtctta 720 tagataccca tatattgata CCATGG gat ggtgttgaag aagctttt ta tacaacaqat 780 cgcgtaarga cggtatcatt ccataaatat ggggaatact ttcctggcac aggagacttg 840 sgggatattg gtg ctggaaa aggcaaatac tatgctgtca attttccaat gtgtgatggt 900 atagatgatg agtcatatgg gcagatattt aagcctatta tctcaaaggt? atggagatg 960 tatcaaccta gtgetgtggt attacagtgt ggtgcagact cattatctgg tgacagactg 1020 ggttgcctca atccaacagt caaaggCcac gctaaatgtg tagaagttgt aaaaactttt 1080 aacttaccat tactgatgct tggaggaggt ggctacacaa tccgtaatgt tgctcgatgt 1140 tggocatatg agactgcagt tgcccttgat tgtgagattc ccaatgagtt gccatataac 1200? = ttactttg gats tctgg accagacctc aaaccgcata ttaqcccttc aaacatgaca 1260 ctccagaata saccagaaca tatggaaaag ataaaacagc gttcgtttga aaatttgcgc 1320 acgttacccc atgcacctgg tgtcca? ETG caagctattc cagaagatgc tgttcatqaa 1380 gacagt? gag atgaagatgg agaagatcca qacaagagaa cttetattcg agcatcagac 1440 cttgtgatga sagcggatag gattctgagg agaattctca atgaaggaga aggaggtcga 1500 ctgatcataa aaaaatgcgg gaaaggagca aagaaagcta gaattgaaga agataagaaa 1560 gaaacagagg acaaaaaaac agacgtCaag gaaqaagata aatccaagga CAAC gtggt 1620 gaaaaaacag ataccaaagg aacc aatca gaacagctca gcaacccctg aattcgacag 168C tccc ccaat ttcagaaaat cattaaaaag aaaatatcga aaggaaaacg ctcccccctc 1740 gaagacttcc ggcttcattt tatactactt tggcatggac tgtatttatt ttcaaatg? g ttttgttttt ctgggcaagt 1800 actctttcgt tttattgtga ttacgsagca gattttccaa 1860 aaatttcttt tctccaccat gctttatgtg atagtattta aaattgatgt gagtcaccat 1920 ctgatctatt gtcaaaaaaa aaagaagtaa ttggcctttc tgagctgaaa aaaaaaaaaa aaaag 1980 1985 < 2IC > 77 < 21 1 > 476 «< 2 ! 2; > DNA < 213 > Unknown < 220 > < 223 > Description of the Unknown Body: Unknown < 400 > 77 ccaccctcct ccccctcccc cggccacttc gctaacttgg tggctgttgt gatgcgtatt 60 cctctagatc c? Agcaccag ccggcgcttc agccccccct ccagcagcct gcagcccggc 120 aaaatgagcg acgtgagccc ggtggtggct gcgcaacagc agcagcaaca gcagcagcag 180 caacagcagc agcaqcagca gcaacagcag cagcagcagc aggaggcggc ggcggcggct 240 gcegcggcag cggcggccgc ggoggcggca gctgcagtgc ccc? Gttgcg gccgccccac 300 ccacggtgga gacaaccgca gatcatcgcc gaccacccgg ccgaactcgt ccgcaccgac 360 agccccaact tcctgtgctc ggtgctgcec tcgcactggc gctgcaacaa gaccctgccc 420 gtggccttca aggtaaqagg ctaccccgcc ccccgccccc ggccgggagc ggcgga 476 < 210 > 78 < 211 > 24 < 212 > DNA 213 > Artificial Sequence < 220 > < 223 > Description of the Artificial Sequence: DNA primer < 4C0 > 78 goactttgga tccgcctttc catg 24 < 21C > 79 < 2il > 22 < 212 DNA < 213 > Artificial Sequence < 220 > < : 223 > Description of the Artificial Sequence: DNA primer < 400 > 79 gttgtgtgct gcagattgtt cc 22 < 210 > 80 < 211 > 21 < 212 > DNA < 213 > Ar-tificial Sequence < 220 > < 223 > Description of the Artificial Sequence: DNA primer < 400 > 80 gaaaaat ggg gatccgaggt g < 210 > 8i < 211 > 20 < 212 > DNA < 213 > Artificial Sequence < 220 > < 222 > Description of the Artificial Sequence: DNA primer «CO 81 gcaggag &at tccgtccatg 20 < 2i0 > 82 < 211 > 5 < 2Y2 > P? VT < 213 > Homo sapiens < 220 > < 221 > IT IS NOT INSURANCE < 222 > (3) < 223 > It can be any amino acid < 400 > 82 Trp Ser Xaa Trp Ser 1 5 < 2il > B3 < 211 > 6 < 212 > PRT < 21I- > Home sapiens < 4C1 > 83 Cys Ser Val Thr Cys Gly *: 5 210 > 84 < 211 > 5 < 2l2 > PRT < 213 > Homo sapiens < 220 > < 221 > IT IS NOT INSURANCE < 222 > (4) < 223 > It can be any amino acid < 40C > 84 Gly Cys Gln Xaa Arg i 5 < 21C > 85 < 211 > 733 < 212 > DNA < 2 3 f'.omo sapiens < 400 > 85 gggatccgga gcccaaatct tctgacaaaa ctcacacatg cccaccgtgc ccagcacctg 60 aattcgaggg tgcaccgtca gtcctcctct tccccccaaa acccaaggac accctcatga 120 tetcccggac tcctgaggtc acatgcgtgg tggtggacgt aagccacqaa gaccctgagg 180 ccaagttcaa ctggtacgtg gacggcgtgg aggtgeataa tqccaaqaca aagccgcggg 240 aggagcagta caacagcacg taccgcgcgg tcagcqtcct caccgtcctg caccaggact 300 ggccgaatgg caaggagtac aagtgcaagg cctccaacaa agccctccea acccccatcg 360 agaaaaccat ctccaaagcc aaagggcagc cccgagaacc acaggtgtac accctgcccc 420 caccecggga tgagctgacc aagaaccagg tcagcctgac ctgcctggtc aaaggcttct 480 catcgccgtg atecaagega qagtgggaga gcaatgggca gccggagaac aactacaaga 540 ccacgcctcc cgtgctggac tccgacggcc ccttcttcct ctacagcaag ctcaccgtgq 600 acaagageag gtggcagcag gggaacgtct tctcatgctc cgcgatgcat caqgctccgc 660 acaaccacca cacgcagaag SCFA cgtctccggg tasatg CCCCC = gtg gat cgacggccgc gactctagag < 21C > 86 < 2il > 86 < 2I2 > DNA 213 > Artificial Sequence < 220 > < 223 > Description of the Artificial Sequence: DNA primer < 400 > 86 gcgcctcgag atttccccga aatetagatt tccccgaaat gatttccccg aaatgactCc 60 cccgaaatat etgccatctc aattas 96 < 210 > 87 < 211 > 27 < 212 > DNA < 213 Artificial Sequence 22 ^ > < 223 > Description of the Artificial Sequence: DNA primer «C3 > 87 gcgqcaagct ttttgcaaag cctasqc 27 < 211 > 2 1 < 212-- DNA 2 3 ^ Artificial Sequence < 220 > < 223 > Description of the Artificial Sequence: PCR fragment < 4 C0'- > 88 cccq qactt ccccgaaatc taga'.ct cc cgaaatgar t tccccgaaat gattr ccccq 6C eaacatctgc catetcaatt agtcagcaac c.itag'cccg cccctoaccc cgcccatccc 120 gcecccaaet ccgcccagtt ccgcccattc tccgccccat ggctgactaa ttttttttat 180 testgeagag gccgaqgccg ccccgqcctc tgagctatc'c cagaagtagt gaggaqgctt 240 271 t ttttggaggc ctaggcr.ttt gcaasaagcL < 210 89 < 211 > 32 < Z1Z > * DN < 12 > Kcaio sapiens < 4C0 > 89 gc ctcgagg gatgacageg atagaacccc gg 32 < 210 > 90 < 211 > 31 < 212 > DNA < 213 > Homo sapiens < 400 > 90 gegaagette gcgactcccc ggatccgcct c 31 < 213 > 91 < 211 > 12 < 212 > DNA < 213"Ho o sapiens < 400 > 91 gsggactttc cc < 21C 92 < 211 > 73 < 212 > DNA < 213 > Home sapiens < 40C > 92 gcggcctcga gggactt c ccggggactt tccggggacc ttccgggact ttccattctg 60 ecacetcaat tag 73 < 210 > 93 < 211 > 27 <; 212 > DNA < 213 > Artificial Sequence < 220 < 223 > Description of the Artificial Sequence: PCR fragment • 00 > 93 gcggcaagct ttctgcaaag cctaggc 27 It is noted that in relation to this date, the best method known by the applicant to carry out the aforementioned invention is that which is clear from the present description of the invention. Having described the invention as above, property is claimed as contained in the following

Claims

1. - An isolated nucleic acid molecule, characterized in that it comprises a polynucleotide selected from the group consisting of: (a) a polynucleotide encoding a polypeptide comprising amino acids 1 to 950 in SEQ. ID NO: 2; (b) a polynucleotide encoding a polypeptide comprising amino acids 2 to 950 in SEQ. ID NO: 2; (c) a polynucleotide encoding a polypeptide comprising amino acids 29 to 950 in SEQ. ID NO: 2; (d) a polynucleotide encoding a polypeptide comprising amino acids 30 to 950 in SEQ. ID NO: 2; (e) a polynucleotide comprising a nucleotide sequence encoding the METH1 polypeptide having the amino acid sequence encoded by the cDNA clone contained in ATCC Deposit No. 209581; - - (f) a polynucleotide comprising a nucleotide sequence encoding the mature METH1 polypeptide having the amino acid sequence encoded by the cDNA clone contained in ATCC Deposit No. 209581; (g) a polynucleotide encoding a polypeptide comprising amino acids 1 to 890 in SEQ. ID NO: 4; (h) a polynucleotide encoding a polypeptide comprising amino acids 2 to 890 in SEQ. ID NO: 4; (i) a polynucleotide encoding a polypeptide comprising amino acids 24 to 890 in SEQ. ID NO: 4; (j) a polynucleotide encoding a polypeptide comprising amino acids 112 to 890 in SEQ. ID NO: 4; (k) a polynucleotide comprising a nucleotide sequence encoding the METH2 polypeptide having the amino acid sequence encoded by the cDNA clone contained in ATCC Deposit No. 209582; (i) a polynucleotide which comprises a nucleotide sequence encoding the mature METH polypeptide having the amino acid sequence encoded by the cDNA region with enid in ATCC Deposit No. 209582; (m) a variant of a 1-year process creates an altered polynucleotide cte (a), (b), (c), (d), (e), (f), (g), (h), (i), (j),. { k), or (i), where: (i) said alteration includes an insertion, deletion, or substitution of nucleotides, or any combination of the same and (ii) the number of alterations is equal to or less than 5% of the total number of nucleotides present in the unaltered polynucleotide; (n) a polynucieotia that encodes the a mocians 235 to 459 in SEC. ID NO: 2; (or) a polynucleotide encoding amino acids 460 to 544 in SEC. I D NO: '2; (p) a polynucleotide coding for amino acids 545 to 598 in SEQ. ID NO: 2; (q) a polynucleotide encoding amino acids B 4 i to 8 9 4 in the SEC. I D NO: 2; (r) a polynucleotide encoding amino acids 895 to 934 in SEQ. ID NO: 2; (s) a polynucleotide encoding amino acids 536 to 613 in SEQ. ID NO: 2; (t) a polynucleotide encoding amino acids 549 to 563 in SEQ. ID NO: 2; (u) a polynucleotide encoding amino acids 214 to 439 in SEQ. ID NO: 4; (v) a polynucleotide encoding amino acids 440 to 529 in SEQ. ID NO: 4; (w) a polynucleotide encoding amino acids 530 to 583 in SEQ. ID NO: 4; (x) a polynucleotide encoding amino acids 837 to 890 in SEQ. ID NO: 4; (y) a polynucleotide encoding amino acids 280 to 606 in SEQ. ID NO: 4; (z) a polynucleotide encoding amino acids 529 to 548 in SEQ. ID NO: 4; and (aa) a nucleotide sequence commentary to any of the nucleotide sequences in (a), (b), (c), (d), (e), (f), (g), (h), (i), (j), (k), (1), (m), (n), (o), (p), (q), (r), (s), (t), (u) ), (v), (w), (x), (y), or (z). - - 2.- An isolated nucleic acid molecule, characterized in that it comprises a polynucleotide that encodes the amino acid sequence of a portion carrying the epitope of the METH1 polypeptide of SEQ. ID

NO: 2 or the METH2 polypeptide of SEC. ID NO: 4

3. - An isolated nucleic acid molecule, characterized in that it comprises a polynucleotide selected from the group consisting of: (a) 50 contiguous nucleotides of the coding region of SEQ. ID NO: 1, provided that said nucleotide sequence is not any of the SECs. ID Nos .: 14-41, or any subfragment thereof; and (b) a nucleotide sequence complementary to the nucleotide sequence in (a).

4. - An isolated nucleic acid molecule, characterized in that it comprises a polynucleotide selected from the group consisting of: (a) 50 contiguous nucleotides of the coding region of SEQ. ID NO: 3, provided that said nucleotide sequence is not SEQ. ID Nos .: 19-22, 24, 42-77, or any subfragment thereof; and (b) a nucleotide sequence complementary to the nucleotide sequence in (a).

5. - A method for preparing a recombinant vector characterized in that it comprises inserting a nucleic acid molecule isolated from the rei indication 1 into a vector in an operable link to a promoter.

6. - A recombinant vector because it is produced by the method of claim 5.

7. - A method for preparing a host cell or recombinant host, characterized in that it comprises introducing the recombinant vector of claim 6 into the host cell or host.

8. - A recombinant host or host cell, characterized in that it is produced by the rei indication method 7.

9. - A recombinant method for producing the METH1 or METH2 polypeptide, characterized in that it comprises culturing the host cell or recombinant host cell of claim 8, under conditions such that said polypeptide is expressed and the polypeptide is recovered.

10. - An isolated polypeptide, characterized in that an amino acid sequence selected from the group consisting of: (a) amino acids 1 to 950 in SEQ. ID NO: 2; (b) amino acids 2 to 950 in SEC. ID NO: 2; (c) amino acids 29 to 950 in SEC. ID O: 2; (d) amino acids 30 to 950 in SEC. ID O: 2; (d) the amino acid sequence of the METH1 polypeptide having the amino acid sequence encoded by the cDNA clone contained in ATCC Deposit No. 209581; (e) the amino acid sequence of the mature METH1 polypeptide having the amino acid sequence encoded by the cDNA clone contained in ATCC Deposit No. 209581; (f) amino acids 1 to 890 in SEC. ID NO: 4; (g) amino acids 2 to 890 in SEC. ID NO: 4; (h) amino acids 24 to 890 in SEC. ID NO: 4; (i) amino acids 112 to 890 in SEC. ID NO: 4; (j) an amino acid sequence of the METH2 polypeptide having the amino acid sequence encoded by the cDNA clone of METH2 contained in the ATCC Deposit No. 209582; (k) an amino acid sequence of the mature METH2 polypeptide having the amino acid sequence encoded by the METH2 cDNA clone contained in ATCC Deposit No. 209582; (1) the amino acid sequence of a variant of the polypeptide created by altering a polypeptide of (a), (b), (c), (d), (e), (f), (g), (h), ( i), (j), or (k), wherein: (i) said alteration includes an insertion, deletion, or substitution of nucleotides or any combination thereof; and (ii) the number of alterations is equal to or less than 5% of the total number of amino acids present in the unaltered amino acid sequence; (m) amino acids 235 to 459 in SEC. ID NO: 2; (n) amino acids 460 to 544 in the SEC. ID NO: 2; (o) amino acids 545 to 598 in SEC. ID NO: '2; (p) amino acids 841 to 894 in SEC. ID NO: 2; - - (q) amino acids 95 934 in SEC. ID NO: 2; (r) amino acids 536 613 in SEQ. ID NO: 2; (s) amino acids 549 563 in SEC. ID NO: 2; (t) amino acids 214 to 439 in SEC. ID NO: 4; (u) amino acids 440 to 529 in SEC. ID NO: 4; (v) amino acids 530 to 583 in the SEC. ID NO: 4; (w) amino acids 37 to 890 in the SEC. ID NO: 4; (x) amino acids 280 to 606 in the SEC. ID NO: 4; (y) amino acids 529 to 548 in the SEC. ID NO: 4; (z) an amino acid sequence of a portion carrying an epitope of any of the polypeptides of (a), (b), (c), (d), (e), (f), (g), (h) ), (i), (j), (k), (1), (m), (n), (o), (p), (q), (r), (s), (t), (u), (v), (w), (x), or (y).

11. The isolated polypeptide according to claim 10, characterized in that it is produced in a recombinant host cell.

12. The isolated polypeptide according to claim 11, characterized in that said recombinant host cell is a mammalian one.

13. - An isolated nucleic acid molecule, characterized in that it comprises a polynucleotide encoding a METH1 or METH2 polypeptide wherein, except for one to fifty substitutions of conserved amino acids, said polypeptide has a sequence selected from the group consisting of: (a) amino acids from approximately 1 to about 950 in the SEC. ID NO: 2; (b) amino acids from about 2 to approximately 950 in the SEC. ID NO: 2; (c) amino acids from about 29 to about 950 in SEC. ID NO: 2; (d) amino acids from about 30 to about 950 in SEC. ID NO: 2; (e) the amino acid sequence of the METH1 polypeptide as encoded by the cDNA clone contained in ATCC Deposit No. 209581; (f) the amino acid sequence of the mature METH1 polypeptide as encoded by the cDNA clone contained in ATCC Deposit No. 209581; (g) amino acids from about 1 to approximately 890 in the SEC. ID NO: 4; (h) amino acids from about 2 to approximately 890 in the SEC. ID NO: 4; (i) amino acids from about 24 to about 890 in SEC. ID NO: 4; (j) amino acids from about 112 to about 890 in SEC. ID NO: 4; (k) the amino acid sequence of the METH2 polypeptide as encoded by the cDNA clone contained in ATCC Deposit No. 209582; and (1) the amino acid sequence of the mature METH2 polypeptide as encoded by the cDNA clone contained in ATCC Deposit No. 209582;

14. - An isolated polypeptide characterized in that, except for substitutions one to fifty of conserved amino acids, said polypeptide has a sequence selected from the group consisting of: (a) amino acids from about 1 to approximately 950 in the.'SEC. ID NO: 2; (b) amino acids from about 2 to approximately 950 in the SEC. ID NO: 2; (c) amino acids from about 29 to about 950 in SEC. ID NO: 2; (d) amino acids from about 30 to about 950 in SEC. ID NO: 2; (e) the amino acid sequence of the METH1 polypeptide as encoded by the cDNA clone contained in ATCC Deposit No. 209581; (f) the amino acid sequence of the mature METH1 polypeptide having the amino acid sequence encoded by the cDNA clone contained in ATCC Deposit No. 209581; (g) amino acids from about 1 to approximately 890 in the SEC. ID NO: 4; (h) amino acids from about 2 to approximately 890 in the SEC. ID NO: 4; (i) amino acids from about 24 to about 890 in SEC. ID NO: 4; (j) amino acids from about 112 to about 890 in SEC. ID NO: 4; (k) the amino acid sequence of the METH2 polypeptide having the amino acid sequence encoded by the cDNA clone contained in ATCC Deposit No. 209582; (1) the amino acid sequence of the mature METH2 polypeptide having the amino acid sequence encoded by the cDNA clone contained in ATCC Deposit No. 209582; and (m) the amino acid sequence of a portion carrying an epitope of any of the polypeptides of (a), (b), (c), (d), (e), (f), (g), ( h), (i), (j), (k), or (1).

15. - An isolated nucleic acid molecule, characterized in that it comprises a polynucleotide at least 95% identical to a polynucleotide selected from the group consisting of: (a) a polynucleotide encoding a polypeptide comprising amino acids 1 to 950 in SEQ. ID NO: 2; (b) a polynucleotide encoding a polypeptide comprising amino acids 2 to 950 in SEQ. ID NO: 2; (c) a polynucleotide encoding a polypeptide comprising amino acids 29 to 950 in SEQ. ID NO: 2; (d) a polynucleotide encoding a polypeptide comprising amino acids 30 to 950 in SEQ. ID NO: 2; (e) a polynucleotide comprising a nucleotide sequence encoding the METH1 polypeptide having the amino acid sequence encoded by the cDNA clone contained in the ATCC Deposit No; 209581; (f) a polynucleotide comprising a nucleotide sequence encoding the mature METH1 polypeptide having the amino acid sequence encoded by the cDNA clone contained in ATCC Deposit No. 209581; (g) a polynucleotide encoding a polypeptide comprising amino acids 1 to 890 in SEQ. ID NO: 4; (h) a polynucleotide encoding a polypeptide comprising amino acids 2 to 890 in SEQ. ID NO: 4; (i) a polynucleotide encoding a polypeptide comprising amino acids 24 to 890 in SEQ. ID NO: 4; (j) a polynucleotide encoding a polypeptide comprising amino acids 112 to 890 in SEQ. ID NO: 4; (k) a polynucleotide comprising a nucleotide sequence encoding the METH2 polypeptide having the amino acid sequence encoded by the cDNA clone contained in ATCC Deposit No. 209582; (1) a polynucleotide comprising a nucleotide sequence encoding the mature METH2 polypeptide having the amino acid sequence encoded by the cDNA clone contained in ATCC Deposit No. 209582; and (m) a nucleotide sequence complementary to any of the nucleotide sequences in (a), (b), (c), (d), (e), (f), (g), (h), ( i), (j), (k), or (1), where: said identity% is calculated using the FASTDB computer program, with the parameters: Matrix = Unitary, k-tuple = 4, Penalty for Des apareami in to = 1, Penalty by Union = 30, Randomization Group Length = 0, Court Record = 1, Penalty by Separation = 5, Penalty by Size of Separation = 0.05, Window Size = 500 or the length of the sequence of nucleotides of matter, whichever is shorter.

16. - An isolated polypeptide, characterized in that it comprises a polypeptide having 95% identity to a polypeptide having an amino acid sequence selected from the group consisting of: (a) amino acids 1 to 950 in SEQ. ID NO: 2; (b) amino acids 2 to 950 in SEC. ID NO: 2; (c) amino acids 29 to 950 in SEC. ID NO: 2; (d) amino acids 30 to 950 in SEC. ID NO: 2; (e) the amino acid sequence of the METH1 polypeptide having the amino acid sequence encoded by the cDNA clone contained in ATCC Deposit No. 209581; - - (f) the amino acid sequence of the mature METH1 polypeptide having the amino acid sequence encoded by the cDNA clone contained in ATCC Deposit No. 209581; (g) amino acids from about 1 to approximately 890 in the SEC. ID NO: 4; (h) amino acids from about 2 to about 890 in SEC. ID NO: 4; (i) amino acids from about 24 to about 890 in SEC. ID NO: 4; (j) amino acids from about 112 to approximately 890 in the SEC. ID NO: 4; (k) the amino acid sequence of the METH2 polypeptide having the amino acid sequence encoded by the cDNA clone contained in the ATCC Deposit No. 209582; and (1) the amino acid sequence of the mature METH2 polypeptide having the amino acid sequence encoded by the cDNA clone contained in ATCC Deposit No. 209582; where said identity is calculated using the FASTDB computer program, with the parameters: Matrix = PAM 0, k-tuple = 2, Penalty for Disapparation = 1, Penalty for Union = 20, Length of Randomization Group = 0, Registration of Cut = 1, Penalty by Separation = 5, Penalty by Size of Separation = 0.05, Window Size = 500 or the length of the amino acid sequence of the matter, whichever is shorter.

17. A method for inhibiting angiogenesis in an individual, characterized in that it comprises administering an effective amount of a polypeptide of claim 10 to said individual.

18. - A polypeptide characterized in that it comprises the amino acid sequence m-n of SEC. ID NO: 2, where m is an integer from 1 to 950, and where n is an integer from 10 to 950. - -

19. - A polypeptide characterized in that it comprises the amino acid sequence m-n of SEC. ID NO: 4, where m is an integer from 10 to 890, and where n is an integer from 10 to 890.