WO2000006738A2 - NUCLEIC ACIDS AND PROTEINS FROM $i(STREPTOCOCCUS PNEUMONIAE) - Google Patents

NUCLEIC ACIDS AND PROTEINS FROM $i(STREPTOCOCCUS PNEUMONIAE) Download PDF

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WO2000006738A2
WO2000006738A2 PCT/GB1999/002452 GB9902452W WO0006738A2 WO 2000006738 A2 WO2000006738 A2 WO 2000006738A2 GB 9902452 W GB9902452 W GB 9902452W WO 0006738 A2 WO0006738 A2 WO 0006738A2
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protein
sequence
polypeptide
defined
sequences
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PCT/GB1999/002452
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French (fr)
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WO2000006738A3 (en
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Richard William Falla Le Page
Jeremy Mark Wells
Sean Bosco Hanniffy
Philip Michael Hansbro
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Microbial Technics Limited
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Priority to GBGB9816336.3A priority Critical patent/GB9816336D0/en
Priority to GB9816336.3 priority
Priority to US12532999P priority
Priority to US60/125,329 priority
Application filed by Microbial Technics Limited filed Critical Microbial Technics Limited
Publication of WO2000006738A2 publication Critical patent/WO2000006738A2/en
Priority claimed from US09/769,744 external-priority patent/US20030134407A1/en
Publication of WO2000006738A3 publication Critical patent/WO2000006738A3/en

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    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K14/00Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/195Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria
    • C07K14/315Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria from Streptococcus (G), e.g. Enterococci
    • C07K14/3156Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria from Streptococcus (G), e.g. Enterococci from Streptococcus pneumoniae (Pneumococcus)
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K2039/51Medicinal preparations containing antigens or antibodies comprising whole cells, viruses or DNA/RNA
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2319/00Fusion polypeptide

Abstract

Novel proteins from Streptococcus pneumoniae are described, together with nucleic acid sequences encoding them. Their use in vaccines and in screening methods is also described.

Description

NUCLEIC ACIDS AND PROTEINS FROM STREPTOCOCCUS PNEUMONIAE

The present invention relates to proteins derived from Streptococcus pneumoniae, nucleic acid molecules encoding such proteins, the use of the nucleic acid and/or proteins as antigens/immunogens and in detection/diagnosis, as well as methods for screening the proteins/nucleic acid sequences as potential anti-microbial targets.

Streptococcus pneumoniae, commonly referred to as the pneumococcus, is an important pathogenic organism. The continuing significance of Streptoccocus pneumoniae infections in relation to human disease in developing and developed countries has been authoritatively reviewed (Fiber, G.R. , Science, 265: 1385-1387 (1994)). That indicates that on a global scale this organism is believed to be the most common bacterial cause of acute respiratory infections, and is estimated to result in 1 million childhood deaths each year, mostly in developing countries (Stansfield, S.K. , Pediatr. Infect. Dis., 6: 622 (1987)). In the USA it has been suggested (Breiman et al, Arch. Intern. Med., 150: 1401 (1990)) that the pneumococcus is still the most common cause of bacterial pneumonia, and that disease rates are particularly high in young children, in the elderly, and in patients with predisposing conditions such as asplenia, heart, lung and kidney disease, diabetes, alcoholism, or with immunosupressive disorders, especially AIDS. These groups are at higher risk of pneumococcal septicaemia and hence meningitis and therefore have a greater risk of dying from pneumococcal infection. The pneumococcus is also the leading cause of otitis media and sinusitis, which remain prevalent infections in children in developed countries, and which incur substantial costs.

The need for effective preventative strategies against pneumococcal infection is highlighted by the recent emergence of penicillin-resistant pneumococci. It has been reported that 6.6% of pneumoccal isolates in 13 US hospitals in 12 states were found to be resistant to penicillin and some isolates were also resistant to other antibiotics including third generation cyclosporins (Schappert, S.M. , Vital and Health Statistics of the Centres for Disease Control/National Centre for Health Statistics, 214: 1 (1992)). The rates of penicillin resistance can be higher (up to 20%) in some hospitals (Breiman et al, J. Am. Med. Assoc , 271: 1831 (1994)). Since the development of penicillin resistance among pneumococci is both recent and sudden, coming after decades during which penicillin remained an effective treatment, these findings are regarded as alarming.

For the reasons given above, there are therefore compelling grounds for considering improvements in the means of preventing, controlling, diagnosing or treating pneumococcal diseases.

Various approaches have been taken in order to provide vaccines for the prevention of pneumococcal infections. Difficulties arise for instance in view of the variety of serotypes (at least 90) based on the structure of the polysaccharide capsule surrounding the organism. Vaccines against individual serotypes are not effective against other serotypes and this means that vaccines must include polysaccharide antigens from a whole range of serotypes in order to be effective in a majority of cases. An additional problem arises because it has been found that the capsular polysaccharides (each of which determines the serotype and is the major protective antigen) when purified and used as a vaccine do not reliably induce protective antibody responses in children under two years of age, the age group which suffers the highest incidence of invasive pneumococcal infection and meningitis.

A modification of the approach using capsule antigens relies on conjugating the polysaccharide to a protein in order to derive an enhanced immune response, particularly by giving the response T-cell dependent character. This approach has been used in the development of a vaccine against Haemophilus influenzae, for instance. There are, however, issues of cost concerning both the multi- polysaccharide vaccines and those based on conjugates.

A third approach is to look for other antigenic components which offer the potential to be vaccine candidates. This is the basis of the present invention. Using a specially developed bacterial expression system, we have been able to identify a group of protein antigens from pneomococcus which are associated with the bacterial envelope or which are secreted.

Thus, in a first aspect the present invention provides a Streptococcus pneumoniae protein or polypeptide having a sequence selected from those shown in table 1.

In a second aspect, the present invention provides a Streptococcus pneumoniae protein or polypeptide having a sequence selected from those shown in table 2.

A protein or polypeptide of the present invention may be provided in substantially pure form. For example, it may be provided in a form which is substantially free of other proteins.

As discussed herein, the proteins and polypeptides of the invention are useful as antigenic material. Such material can be "antigenic" and/or "immunogenic" . Generally, "antigenic" is taken to mean that the protein or polypeptide is capable of being used to raise antibodies or indeed is capable of inducing an antibody response in a subject. "Immunogenic" is taken to mean that the protein or polypeptide is capable of eliciting a protective immune response in a subject. Thus, in the latter case, the protein or polypeptide may be capable of not only generating an antibody response but, in addition, a non-antibody based immune response. The skilled person will appreciate that homologues or derivatives of the proteins or polypeptides of the invention will also find use in the context of the present invention, ie as antigenic/immunogenic material. Thus, for instance proteins or polypeptides which include one or more additions, deletions, substitutions or the like are encompassed by the present invention. In addition, it may be possible to replace one amino acid with another of similar "type" . For instance replacing one hydrophobic amino acid with another. One can use a program such as the CLUSTAL program to compare amino acid sequences. This program compares amino acid sequences and finds the optimal alignment by inserting spaces in either sequence as appropriate. It is possible to calculate amino acid identity or similarity (identity plus conservation of amino acid type) for an optimal alignment. A program like BLASTx will align the longest stretch of similar sequences and assign a value to the fit. It is thus possible to obtain a comparison where several regions of similarity are found, each having a different score. Both types of identity analysis are contemplated in the present invention.

In the case of homologues and derivatives, the degree of identity with a protein or polypeptide as described herein is less important than that the homologue or derivative should retain the antigenicity or immunogenicity of the original protein or polypeptide. However, suitably, homologues or derivatives having at least 60% similarity (as discussed above) with the proteins or polypeptides described herein are provided. Preferably, homologues or derivatives having at least 70% similarity, more preferably at least 80% similarity are provided. Most preferably, homologues or derivatives having at least 90% or even 95% similarity are provided.

In an alternative approach, the homologues or derivatives could be fusion proteins, incorporating moieties which render purification easier, for example by effectively tagging the desired protein or polypeptide. It may be necessary to remove the "tag" or it may be the case that the fusion protein itself retains sufficient antigenicity to be useful.

In an additional aspect of the invention there are provided antigenic/immunogenic fragments of the proteins or polypeptides of the invention, or of homologues or derivatives thereof.

For fragments of the proteins or polypeptides described herein, or of homologues or derivatives thereof, the situation is slightly different. It is well known that is possible to screen an antigenic protein or polypeptide to identify epitopic regions, ie those regions which are responsible for the protein or polypeptide 's antigenicity or immunogenicity.

Methods for carrying out such screening are well known in the art. Thus, the fragments of the present invention should include one or more such epitopic regions or be sufficiently similar to such regions to retain their antigenic/immunogenic properties.

Thus, for fragments according to the present invention the degree of identity is perhaps irrelevant, since they may be 100% identical to a particular part of a protein or polypeptide, homologue or derivative as described herein. The key issue, once again, is that the fragment retains the antigenic/immunogenic properties.

Thus, what is important for homologues, derivatives and fragments is that they possess at least a degree of the antigenicity/immunogenicity of the protein or polypeptide from which they are derived.

Gene cloning techniques may be used to provide a protein of the invention in substantially pure form. These techniques are disclosed, for example, in J. Sambrook et al Molecular Cloning 2nd Edition, Cold Spring Harbor Laboratory Press (1989). Thus, in a third aspect, the present invention provides a nucleic acid molecule comprising or consisting of a sequence which is:

(i) any of the DNA sequences set out in Table 1 or their RNA equivalents;

(ii) a sequence which is complementary to any of the sequences of (i);

(iii) a sequence which codes for the same protein or polypeptide, as those sequences of (i) or (ii);

(iv) a sequence which has substantial identity with any of those of (i), (ii) and (iii);

(v) a sequence which codes for a homologue, derivative or fragment of a protein as defined in Table 1.

In a fourth aspect the present invention provides a nucleic acid molecule comprising or consisting of a sequence which is:

(i) any of the DNA sequences set out in Table 2 or their RNA equivalents;

(ii) a sequence which is complementary to any of the sequences of (i);

(iii) a sequence which codes for the same protein or polypeptide, as those sequences of (i) or (ii);

(iv) a sequence which has substantial identity with any of those of (i), (ii) and (iii); or (v) a sequence which codes for a homologue, derivative or fragment of a protein as defined in Table 2.

The nucleic acid molecules of the invention may include a plurality of such sequences, and/or fragments. The skilled person will appreciate that the present invention can include novel variants of those particular novel nucleic acid molecules which are exemplified herein. Such variants are encompassed by the present invention. These may occur in nature, for example because of strain variation. For example, additions, substitutions and/or deletions are included. In addition, and particularly when utilising microbial expression systems, one may wish to engineer the nucleic acid sequence by making use of known preferred codon usage in the particular organism being used for expression. Thus, synthetic or non-naturally occurring variants are also included within the scope of the invention.

The term "RNA equivalent" when used above indicates that a given RNA molecule has a sequence which is complementary to that of a given DNA molecule (allowing for the fact that in RNA "U" replaces "T" in the genetic code).

When comparing nucleic acid sequences for the purposes of determining the degree of homology or identity one can use programs such as BESTFIT and GAP (both from the Wisconsin Genetics Computer Group (GCG) software package) BESTFIT, for example, compares two sequences and produces an optimal alignment of the most similar segments. GAP enables sequences to be aligned along their whole length and finds the optimal alignment by inserting spaces in either sequence as appropriate. Suitably, in the context of the present invention when discussing identity of nucleic acid sequences, the comparison is made by alignment of the sequences along their whole length. Preferably, sequences which have substantial identity have at least 50% sequence identity, desirably at least 75% sequence identity and more desirably at least 90 or at least 95% sequence identity with said sequences. In some cases the sequence identity may be 99% or above.

Desirably, the term "substantial identity" indicates that said sequence has a greater degree of identity with any of the sequences described herein than with prior art nucleic acid sequences.

It should however be noted that where a nucleic acid sequence of the present invention codes for at least part of a novel gene product the present invention includes within its scope all possible sequence coding for the gene product or for a novel part thereof.

The nucleic acid molecule may be in isolated or recombinant form. It may be incorporated into a vector and the vector may be incorporated into a host. Such vectors and suitable hosts form yet further aspects of the present invention.

Therefore, for example, by using probes based upon the nucleic acid sequences provided herein, genes in Streptococcus pneumoniae can be identified. They can then be excised using restriction enzymes and cloned into a vector. The vector can be introduced into a suitable host for expression.

Nucleic acid molecules of the present invention may be obtained from S. pneumoniae by the use of appropriate probes complementary to part of the sequences of the nucleic acid molecules. Restriction enzymes or sonication techniques can be used to obtain appropriately sized fragments for probing. Alternatively PCR techniques may be used to amplify a desired nucleic acid sequence. Thus the sequence data provided herein can be used to design two primers for use in PCR so that a desired sequence, including whole genes or fragments thereof, can be targeted and then amplified to a high degree.

Typically primers will be at least 15-25 nucleotides long.

As a further alternative chemical synthesis may be used. This may be automated. Relatively short sequences may be chemically synthesised and ligated together to provide a longer sequence.

There is another group of proteins from S. pneumoniae which have been identified using the bacterial expression system described herein. These are known proteins from S. pneumoniae, which have not previously been identified as antigenic proteins. The amino acid sequences of this group of proteins, together with DNA sequences coding for them are shown in Table 3. These proteins, or homologues, derivatives and/or fragments thereof also find use as antigens/immunogens. Thus, in another aspect the present invention provides the use of a protein or polypeptide having a sequence selected from those shown in Tables 1-3, or homologues, derivatives and/or fragments thereof, as an immunogen/antigen.

In yet a further aspect the present invention provides an immunogenic/antigenic composition comprising one or more proteins or polypeptides selected from those whose sequences are shown in Tables 1-3, or homologues or derivatives thereof, and/or fragments of any of these. In preferred embodiments, the immunogenic/antigenic composition is a vaccine or is for use in a diagnostic assay.

In the case of vaccines suitable additional excipients, diluents, adjuvants or the like may be included. Numerous examples of these are well known in the art.

It is also possible to utilise the nucleic acid sequences shown in Tables 1-3 in the preparation of so-called DNA vaccines. Thus, the invention also provides a vaccine composition comprising one or more nucleic acid sequences as defined herein. DNA vaccines are described in the art (see for instance, Donnelly et al , Ann. Rev. Immunol., 15:617-648 (1997)) and the skilled person can use such art described techniques to produce and use DNA vaccines according to the present invention.

As already discussed herein the proteins or polypeptides described herein, their homologues or derivatives, and/or fragments of any of these, can be used in methods of detecting/diagnosing S. pneumoniae. Such methods can be based on the detection of antibodies against such proteins which may be present in a subject. Therefore the present invention provides a method for the detection/diagnosis of S.pneumoniae which comprises the step of bringing into contact a sample to be tested with at least one protein, or homologue, derivative or fragment thereof, as described herein. Suitably, the sample is a biological sample, such as a tissue sample or a sample of blood or saliva obtained from a subject to be tested.

In an alternative approach, the proteins described herein, or homologues, derivatives and/or fragments thereof, can be used to raise antibodies, which in turn can be used to detect the antigens, and hence S.pneumoniae. Such antibodies form another aspect of the invention. Antibodies within the scope of the present invention may be monoclonal or polyclonal.

Polyclonal antibodies can be raised by stimulating their production in a suitable animal host (e.g. a mouse, rat, guinea pig, rabbit, sheep, goat or monkey) when a protein as described herein, or a homologue, derivative or fragment thereof, is injected into the animal. If desired, an adjuvant may be administered together with the protein. Well- known adjuvants include Freund's adjuvant (complete and incomplete) and aluminium hydroxide. The antibodies can then be purified by virtue of their binding to a protein as described herein.

Monoclonal antibodies can be produced from hybridomas. These can be formed by fusing myeloma cells and spleen cells which produce the desired antibody in order to form an immortal cell line. Thus the well-known Kohler & Milstein technique (Nature 256 (1975)) or subsequent variations upon this technique can be used.

Techniques for producing monoclonal and polyclonal antibodies that bind to a particular polypeptide/protein are now well developed in the art. They are discussed in standard immunology textbooks, for example in Roitt et al, Immunology second edition (1989), Churchill Livingstone, London.

In addition to whole antibodies, the present invention includes derivatives thereof which are capable of binding to proteins etc as described herein. Thus the present invention includes antibody fragments and synthetic constructs. Examples of antibody fragments and synthetic constructs are given by Dougall et al in Tibtech 12 372-379 (September 1994).

Antibody fragments include, for example, Fab, F(ab')2 and Fv fragments. Fab fragments (These are discussed in Roitt et al [supra] ). Fv fragments can be modified to produce a synthetic construct known as a single chain Fv (scFv) molecule. This includes a peptide linker covalently joining Vh and V, regions, which contributes to the stability of the molecule. Other synthetic constructs that can be used include CDR peptides. These are synthetic peptides comprising antigen-binding deteirninants. Peptide mimetics may also be used. These molecules are usually conformationally restricted organic rings that mimic the structure of a CDR loop and that include antigen-interactive side chains.

Synthetic constructs include chimaeric molecules. Thus, for example, humanised (or primatised) antibodies or derivatives thereof are within the scope of the present invention. An example of a humanised antibody is an antibody having human framework regions, but rodent hypervariable regions. Ways of producing chimaeric antibodies are discussed for example by Morrison et al in PNAS, 81, 6851-6855 (1984) and by Takeda et al in Nature. 314, 452-454 (1985).

Synthetic constructs also include molecules comprising an additional moiety that provides the molecule with some desirable property in addition to antigen binding. For example the moiety may be a label (e.g. a fluorescent or radioactive label). Alternatively, it may be a pharmaceutically active agent.

Antibodies, or derivatives thereof, find use in detection/diagnosis of S.pneumoniae. Thus, in another aspect the present invention provides a method for the detection/diagnosis of S.pneumoniae which comprises the step of bringing into contact a sample to be tested and antibodies capable of binding to one or more proteins described herein, or to homologues, derivatives and/or fragments thereof.

In addition, so-called "Affibodies" may be utilised. These are binding proteins selected from combinatorial libraries of an alpha-helical bacterial receptor domain (Nord et al , ) Thus, Small protein domains, capable of specific binding to different target proteins can be selected using combinatorial approaches.

It will also be clear that the nucleic acid sequences described herein may be used to detect/diagnose S.pneumoniae. Thus, in yet a further aspect, the present invention provides a method for the detection/diagnosis of S.pneumoniae which comprises the step of bringing into contact a sample to be tested with at least one nucleic acid sequence as described herein. Suitably, the sample is a biological sample, such as a tissue sample or a sample of blood or saliva obtained from a subject to be tested. Such samples may be pre-treated before being used in the methods of the invention.

Thus, for example, a sample may be treated to extract DNA. Then, DNA probes based on the nucleic acid sequences described herein (ie usually fragments of such sequences) may be used to detect nucleic acid from S.pneumoniae.

In additional aspects, the present invention provides:

(a) a method of vaccinating a subject against S.pneumoniae which comprises the step of administering to a subject a protein or polypeptide of the invention, or a derivative, homologue or fragment thereof, or an immunogenic composition of the invention;

(b) a method of vaccinating a subject against S.pneumoniae which comprises the step of administering to a subject a nucleic acid molecule as defined herein;

(c) a method for the prophylaxis or treatment of S.pneumoniae infection which comprises the step of administering to a subject a protein or polypeptide of the invention, or a derivative, homologue or fragment thereof, or an immunogenic composition of the invention;

(d) a method for the prophylaxis or treatment of S.pneumoniae infection which comprises the step of administering to a subject a nucleic acid molecule as defined herein; (e) a kit for use in detecting/diagnosing S.pneumoniae infection comprising one or more proteins or polypeptides of the invention, or homologues, derivatives or fragments thereof, or an antigenic composition of the invention; and

(f) a kit for use in detecting/diagnosing S.pneumoniae infection comprising one or more nucleic acid molecules as defined herein.

Given that we have identified a group of important proteins, such proteins are potential targets for anti-microbial therapy. It is necessary, however, to determine whether each individual protein is essential for the organism's viability. Thus, the present invention also provides a method of determining whether a protein or polypeptide as described herein represents a potential anti-microbial target which comprises antagonising, inhibiting or otherwise interfering with the function or expression of said protein and determining whether S.pneumoniae is still viable.

A suitable method for inactivating the protein is to effect selected gene knockouts, ie prevent expression of the protein and determine whether this results in a lethal change. Suitable methods for carrying out such gene knockouts are described in Li et al , P.N.A.S., 94: 13251-13256 (1997) and Kolkman et al , 178:3736- 3741 (1996).

In a final aspect the present invention provides the use of an agent capable of antagonising, inhibiting or otherwise interfering with the function or expression of a protein or polypeptide of the invention in the manufacture of a medicament for use in the treatment or prophylaxis of S.pneumoniae infection.

As mentioned above, we have used a bacterial expression system as a means of identifying those proteins which are surface associated, secreted or exported and thus, would find use as antigens.

The information necessary for the secretion/export of proteins has been extensively studied in bacteria. In the majority of cases, protein export requires a signal peptide to be present at the N-terminus of the precursor protein so that it becomes directed to the translocation machinery on the cytoplasmic membrane. During or after translocation, the signal peptide is removed by a membrane associated signal peptidase. Ultimately the localization of the protein (i.e. whether it be secreted, an integral membrane protein or attached to the cell wall) is determined by sequences other than the leader peptide itself.

We are specifically interested in surface located or exported proteins as these are likely to be antigens for use in vaccines, as diagnostic reagents or as targets for therapy with novel chemical entities. We have therefore developed a screening vector-system in Lactococcus lactis that permits genes encoding exported proteins to be identified and isolated. We provide below a representative example showing how given novel surface associated proteins from Streptococcus pneumoniae have been identified and characterized. The screening vector incorporates the staphylococcal nuclease gene nuc lacking its own export signal as a secretion reporter. Staphylococcal nuclease is a naturally secreted heat-stable, monomeric enzyme which has been efficiently expressed and secreted in a range of Gram positive bacteria (Shortle, Gene, 22:181-189 (1983); Kovacevic et al. , J. Bacteriol, 162:521-528 (1985); Miller et al., J. Bacteriol , 169:3508-3514 (1987); Liebl et al. , J. Bacteriol, 174:1854-1861 (1992); Le Loir et al, J. Bacteriol, 176:5135-5139 (1994); Poquet et al , J. Bacteriol, 180:1904-1912 (1998)).

Recently, Poquet et al. ((1998), supra) have described a screening vector incorporating the nuc gene lacking its own signal leader as a reporter to identify exported proteins in Gram positive bacteria, and have applied it to L. lactis. This vector (pFUN) contains the pAMβl replicon which functions in a broad host range of Gram-positive bacteria in addition to the ColEl replicon that promotes replication in Escherichia coli and certain other Gram negative bacteria. Unique cloning sites present in the vector can be used to generate transcriptional and translational fusions between cloned genomic DNA fragments and the open reading frame of the truncated nuc gene devoid of its own signal secretion leader. The nuc gene makes an ideal reporter gene because the secretion of nuclease can readily be detected using a simple and sensitive plate test: Recombinant colonies secreting the nuclease develop a pink halo whereas control colonies remain white (Shortle, (1983), supra; Le Loir et al, (1994), supra).

Thus, the invention will now be described with reference to the following representative example, which provides details of how the proteins, polypeptides and nucleic acid sequences described herein identified as antigenic targets.

We describe herein the construction of three reporter vectors and their use in L. lactis to identify and isolate genomic DNA fragments from Streptococcus pneumoniae encoding secreted or surface associated proteins.

The invention will now be described with reference to the examples, which should not be construed as in any way limiting the invention. The examples refer to the figures in which:

Figure 1: shows the results of a number of DNA vaccine trials; and

Figure 2: shows the results of further DNA vaccine trials.

EXAMPLE 1

(i) Construction of the pTREPl-nuc series of reporter vectors (a) Construction of expression plasmid pTREPl

The pTREPl plasmid is a high-copy number (40-80 per cell) theta-replicating gram positive plasmid, which is a derivative of the pTREX plasmid which is itself a derivative of the previously published pIL253 plasmid. pIL253 incorporates the broad Gram-positive host range replicon of pAMβl (Simon and Chopin, Biochimie, 70:559-567 (1988)) and is non-mobilisable by the L lactis sex-factor. pIL253 also lacks the tra function which is necessary for transfer or efficient mobilisation by conjugative parent plasmids exemplified by pIL501. The Enterococcal pAMβl replicon has previously been transferred to various species including Streptococcus, Lactobacillus and Bacillus species as well as Clostridium acetobutylicum, (Oultram and Klaenhammer, FEMS Microbiological Letters, 27:129-134 (1985); Gibson et al , (1979); LeBlanc et al , Proceedings of the National Academy of Science USA, 75:3484-3487 (1978)) indicating the potential broad host range utility. The pTREPl plasmid represents a constitutive transcription vector.

The pTREX vector was constructed as follows. An artificial DNA fragment containing a putative RNA stabilising sequence, a translation initiation region (TIR), a multiple cloning site for insertion of the target genes and a transcription terminator was created by annealing 2 complementary oligonucleotides and extending with Tfl DNA polymerase. The sense and anti-sense oligonucleotides contained the recognition sites for Nhel and BamHI at their 5 ' ends respectively to facilitate cloning. This fragment was cloned between the Xbal and BamHI sites in pUC19NT7, a derivative of pUC19 which contains the T7 expression cassette from pLETl (Wells et al , J. Appl. Bacteriol. , 74:629-636 (1993)) cloned between the EcoRI and Hindlll sites. The resulting construct was designated pUCLEX. The complete expression cassette of pUCLEX was then removed by cutting with Hindlll and blunting followed by cutting with EcoRI before cloning into EcoRI and Sad (blunted) sites of pIL253 to generate the vector pTREX (Wells and Schofield, In Current advances in metabolism, genetics and applications -NATO ASI Series, H 98:37-62 (1996)). The putative RNA stabilising sequence and TIR are derived from the Escherichia coli T7 bacteriophage sequence and modified at one nucleotide position to enhance the complementarity of the Shine Dalgarno (SD) motif to the ribosomal 16s RNA of Lactococcus lactis (Schofield et al. pers. coms. University of Cambridge Dept. Pathology.).

A Lactococcus lactis MG1363 chromosomal DNA fragment exhibiting promoter activity which was subsequently designated P7 was cloned between the EcoRI and Bglll sites present in the expression cassette, creating pTREX7. This active promoter region had been previously isolated using the promoter probe vector pSB292 (Waterfield et al, Gene, 165:9-15 (1995)). The promoter fragment was amplified by PCR using the Vent DNA polymerase according to the manufacturer.

The pTREPl vector was then constructed as follows. An artificial DNA fragment which included a transcription terminator, the forward pUC sequencing primer, a promoter multiple -cloning site region and a universal translation stop sequence was created by annealing two overlapping partially complementary synthetic oligonucleotides together and extending with sequenase according to manufacturers instructions. The sense and anti-sense (pTREPF and pTREPpJ oligonucleotides contained the recognition sites for EcoRV and BamHI at their 5 ' ends respectively to facilitate cloning into pTREX7. The transcription terminator was that of the Bacillus penicillinase gene, which has been shown to be effective in Lactococcus (Jos et al, Applied and Environmental Microbiology, 50:540-542 (1985)). This was considered necessary as expression of target genes in the pTREX vectors was observed to be leaky and is thought to be the result of cryptic promoter activity in the origin region (Schofield et al. pers. coms. University of Cambridge Dept. Pathology.). The forward pUC primer sequencing was included to enable direct sequencing of cloned DNA fragments. The translation stop sequence which encodes a stop codon in 3 different frames was included to prevent translational fusions between vector genes and cloned DNA fragments. The pTREX7 vector was first digested with EcoRI and blunted using the 5' - 3' polymerase activity of T4 DNA polymerase (NEB) according to manufacturer's instructions. The EcoRI digested and blunt ended pTREX7 vector was then digested with Bgl II thus removing the P7 promoter. The artificial DNA fragment derived from the annealed synthetic oligonucleotides was then digested with EcoRV and Bam HI and cloned into the EcoRI(blunted)-Bgl II digested pTREX7 vector to generate pTREP. A Lactococcus lactis MG1363 chromosomal promoter designated PI was then cloned between the EcoRI and Bglll sites present in the pTREP expression cassette forming pTREPl. This promoter was also isolated using the promoter probe vector pSB292 and characterised by Waterfield et al , (1995), supra. The PI promoter fragment was originally amplified by PCR using vent DNA polymerase according to manufacturers instructions and cloned into the pTREX as an EcoRI-Bglll DNA fragment. The EcoRI-Bglll PI promoter containing fragment was removed from pTREXl by restriction enzyme digestion and used for cloning into pTREP (Schofield et al. pers. coms. University of Cambridge, Dept. Pathology.).

(b) PCR amplification of the S. aureus nuc gene.

The nucleotide sequence of the S. aureus nuc gene (EMBL database accession number V01281) was used to design synthetic oligonucleotide primers for PCR amplification. The primers were designed to amplify the mature form of the nuc gene designated nucA which is generated by proteolytic cleavage of the N-terminal 19 to 21 amino acids of the secreted propeptide designated Snase B (Shortle, (1983), supra). Three sense primers (nucSl, nucS2 and nucS3, Appendix 1) were designed, each one having a blunt-ended restriction endonuclease cleavage site for EcoRV or Smal in a different reading frame with respect to the nuc gene. Additionally Bglll and BamHI were incorporated at the 5' ends of the sense and anti-sense primers respectively to facilitate cloning into BamHI and Bglll cut pTREPl. The sequences of all the primers are given in Appendix 1. Three nuc gene DNA fragments encoding the mature form of the nuclease gene (NucA) were amplified by PCR using each of the sense primers combined with the anti-sense primer described above. The nuc gene fragments were amplified by PCR using S. aureus genomic DNA template, Vent DNA Polymerase (NEB) and the conditions recommended by the manufacturer. An initial denaturation step at 93 C for 2 min was followed by 30 cycles of denaturation at 93 C for 45 sec, annealing at 50 C for 45 seconds, and extension at 73 C for 1 minute and then a final 5 min extension step at 73 C. The PCR amplified products were purified using a Wizard clean up column (Promega) to remove unincorporated nucleotides and primers.

(c) Construction of the pTREPl -nuc vectors

The purified nuc gene fragments described in section b were digested with Bgl II and BamHI using standard conditions and ligated to BamHI and Bglll cut and dephosphorylated pTREPl to generate the pTREPl -nuc 1, pTREPl -nuc2 and pTREPl -nuc3 series of reporter vectors. General molecular biology techniques were carried out using the reagents and buffer supplied by the manufacture or using standard conditions(Sambrook and Maniatis, (1989), supra). In each of the pTREPl - nuc vectors the expression cassette comprises a transcription terminator, lactococcal promoter PI, unique cloning sites (Bglll, EcoRV or Smal) followed by the mature form of the nuc gene and a second transcription terminator. Note that the sequences required for translation and secretion of the nuc gene were deliberately excluded in this construction. Such elements can only be provided by appropriately digested foreign DNA fragments (representing the target bacterium) which can be cloned into the unique restriction sites present immediately upstream of the nuc gene. In possessing a promoter, the pTREPl -nuc vectors differ from the pFUN vector described by Poquet et al (1998), supra, which was used to identify L. lactis exported proteins by screening directly for Nuc activity directly in L. lactis. As the pFUN vector does not contain a promoter upstream of the nuc open reading frame the cloned genomic DNA fragment must also provide the signals for transcription in addition to those elements required for translation initiation and secretion of Nuc. This limitation may prevent the isolation of genes that are distant from a promoter for example genes which are within polycistronic operons. Additionally there can be no guarantee that promoters derived from other species of bacteria will be recognised and functional in L. lactis. Certain promoters may be under stringent regulation in the natural host but not in L. lactis. In contrast, the presence of the PI promoter in the pTREPl -nuc series of vectors ensures that promoter less DNA fragments (or DNA fragments containing promoter sequences not active in L. lactis) will still be transcribed.

(d) Screening for secreted proteins in S. pneumoniae

Genomic DNA isolated from S. pneumoniae was digested with the restriction enzyme Tru9I. This enzyme which recognises the sequence 5'- TTAA -3' was used because it cuts A/T rich genomes efficiently and can generate random genomic DNA fragments within the preferred size range (usually averaging 0.5 - 1.0 kb). This size range was preferred because there is an increased probability that the PI promoter can be utilised to transcribe a novel gene sequence. However, the PI promoter may not be necessary in all cases as it is possible that many Streptococcal promoters are recognised in L. lactis. DNA fragments of different size ranges were purified from partial Tru9I digests of S. pneumoniae genomic DNA. As the Tru 91 restriction enzyme generates staggered ends the DNA fragments had to be made blunt ended before ligation to the EcoRV or Smal cut pTREPl -nuc vectors. This was achieved by the partial fill-in enzyme reaction using the 5 '-3' polymerase activity of Klenow enzyme. Briefly Tru9I digested DNA was dissolved in a solution (usually between 10-20 μl in total) supplemented with T4 DNA ligase buffer (New England Biolabs; NEB) (IX) and 33 μM of each of the required dNTPs, in this case dATP and dTTP. Klenow enzyme was added (1 unit Klenow enzyme (NEB) per μg of DNA) and the reaction incubated at 25°C for 15 minutes. The reaction was stopped by incubating the mix at 75°C for 20 minutes. EcoRV or Smal digested pTREP-nuc plasmid DNA was then added (usually between 200-400 ng). The mix was then supplemented with 400 units of T4 DNA ligase (NEB) and T4 DNA ligase buffer (IX) and incubated overnight at 16°C. The ligation mix was precipitated directly in 100% Ethanol and 1/10 volume of 3M sodium acetate (pH 5.2) and used to transform L. lactis MG1363 (Gasson, 1983). Alternatively, the gene cloning site of the pTREP-nuc vectors also contains a Bglll site which can be used to clone for example Sau3AI digested genomic DNA fragments. L. lactis transformant colonies were grown on brain heart infusion agar and nuclease secreting (Nuc+) clones were detected by a toluidine blue-DNA-agar overlay (0.05 M Tris pH 9.0, 10 g of agar per litre, 10 g of NaCl per liter, 0.1 mM CaC12, 0.03% wt/vol. salmon sperm DNA and 90 mg of Toluidine blue O dye) essentially as described by Shortle, 1983, supra and Le Loir et al, 1994, supra). The plates were then incubated at 37°C for up to 2 hours. Nuclease secreting clones develop an easily identifiable pink halo. Plasmid DNA was isolated from Nuc+ recombinant L. lactis clones and DNA inserts were sequenced on one strand using the NucSeq sequencing primer described in Appendix 1 , which sequences directly through the DNA insert.

Isolation of Genes Encoding Exported Proteins from S. pneumoniae

A large number of gene sequences putatively encoding exported proteins in S. pneumoniae have been identified using the nuclease screening system. These have now been further analysed to remove artefacts. The sequences identified using the screening system have been analysed using a number of parameters.

1. All putative surface proteins were analysed for leader/signal peptide sequences using the software programs Sequencher (Gene Codes Corporation) and DNA Strider (Marck, Nucleic Acids Res., 16:1829-1836 (1988)). Bacterial signal peptide sequences share a common design. They are characterised by a short positively charged N-terminus (N region) immediately preceding a stretch of hydrophobic residues (central portion-h region) followed by a more polar C-terminal portion which contains the cleavage site (c-region). Computer software is available which allows hydropathy profiling of putative proteins and which can readily identify the very distinctive hydrophobic portion (h-region) typical of leader peptide sequences. In addition, the sequences were checked for the presence of or absence of a potential ribosomal binding site (Shine-Dalgarno motif) required for translation initiation of the putative nuc reporter fusion protein.

2. All putative surface protein sequences were also matched with all of the protein/DNA sequences using the publicly databases [OWL-proteins inclusive of SwissProt and GenBank translations] . This allows us to identify sequences similar to known genes or homologues of genes for which some function has been ascribed. Hence it has been possible to predict a function for some of the genes identified using the LEEP system and to unequivocally establish that the system can be used to identify and isolate gene sequences of surface associated proteins. We should also be able to confirm that these proteins are indeed surface related and not artifacts. The LEEP system has been used to identify novel gene targets for vaccine and therapy. 3. Some of the genes identified proteins did not possess a typical leader peptide sequence and did not show homology with any DNA/protein sequences in the database. Indeed these proteins may indicate the primary advantage of our screening method, i.e. the isolation of atypical surface-related proteins, which may have been missed in all previously described screening protocols or approaches based on sequence homology searches.

In all cases, only partial gene sequences were initially obtained. Full length genes were obtained in all cases by reference to the TIGR S.pneumoniae database

(www@tigr.org). Thus, by matching the originally obtained partial sequences with the database, we were able to identify the full length gene sequences. In this way, as described herein, three groups of genes were clearly identified, ie a group of genes encoding previously unidentified S.pneumoniae proteins, a second group exhibiting some homology with known proteins from a variety of sources and a third group which encoded known S.pneumoniae proteins, which were, however, not known as antigens.

Example 2: Vaccine trials

pcDNA3.1+ as a DNA vaccine vector

pcDNA3.1 + The vector chosen for use as a DNA vaccine vector was pcDNA3.1 (Invitrogen) (actually pcDNA3.1 + , the forward orientation was used in all cases but may be referred to as pcDNA3.1 here on). This vector has been widely and successfully employed as a host vector to test vaccine candidate genes to give protection against pathogens in the literature (Zhang, et al , Kurar and Splitter, Anderson et ah). The vector was designed for high-level stable and non-replicative transient expression in mammalian cells. pcDNA3.1 contains the ColEl origin of replication which allows convenient high-copy number replication and growth in E. coli. This in turn allows rapid and efficient cloning and testing of many genes. The pcDNA3.1 vector has a large number of cloning sites and also contains the gene encoding ampicillin resistance to aid in cloning selection and the human cytomegalovirus (CMV) immediate-early promoter/enhancer which permits efficient, high-level expression of the recombinant protein. The CMV promoter is a strong viral promoter in a wide range of cell types including both muscle and immune (antigen presenting) cells. This is important for optimal immune response as it remains unknown as to which cells types are most important in generating a protective response in vivo. A T7 promoter upstream of the multiple cloning site affords efficient expression of the modified insert of interest and which allows in vitro transcription of a cloned gene in the sense orientation.

Zhang, D. , Yang, X., Berry, J. Shen, C, McClarty, G. and Brunham, R.C. (1997) "DNA vaccination with the major outer-membrane protein genes induces acquired immunity to Chlamydia trachomatis (mouse pneumonitis) infection" . Infection and Immunity, 176, 1035-40.

Kurar, E. and Splitter, G.A. (1997) "Nucleic acid vaccination of Brucella abortus ribosomal L7/L12 gene elicits immune response". Vaccine, 15, 1851-57.

Anderson, R. , Gao, X.-M. , Papakonstantinopoulou, A., Roberts, M. and Dougan, G. (1996) "Immune response in mice following immunisation with DNA encoding fragment C of tetanus toxin" . Infection and Immunity, 64, 3168-3173.

Preparation of DNA vaccines

Oligonucleotide primers were designed for each individual gene of interest derived using the LEEP system. Each gene was examined thoroughly, and where possible, primers were designed such that they targeted that portion of the gene thought to encode only the mature portion of the gene protein. It was hoped that expressing those sequences that encode only the mature portion of a target gene protein, would facilitate its correct folding when expressed in mammalian cells. For example, in the majority of cases primers were designed such that putative N-terminal signal peptide sequences would not be included in the final amplification product to be cloned into the pcDNA3.1 expression vector. The signal peptide directs the polypeptide precursor to the cell membrane via the protein export pathway where it is normally cleaved off by signal peptidase I (or signal peptidase II if a lipoprotein). Hence the signal peptide does not make up any part of the mature protein whether it be displayed on the surface of the bacteria surface or secreted. Where an N-terminal leader peptide sequence was not immediately obvious, primers were designed to target the whole of the gene sequence for cloning and ultimately, expression in pcDNA3.1.

Having said that, however, other additional features of proteins may also affect the expression and presentation of a soluble protein. DNA sequences encoding such features in the genes encoding the proteins of interest were excluded during the design of oligonucleotides. These features included:

1. LPXTG cell wall anchoring motifs.

2. LXXC ipoprotein attachment sites.

3. Hydrophobic C-terminal domain. 4. Where no N-terminal signal peptide or LXXC was present the start codon was excluded.

5. Where no hydrophobic C-terminal domain or LPXTG motif was present the stop codon was removed.

Appropriate PCR primers were designed for each gene of interest and any and all of the regions encoding the above features was removed from the gene when designing these primers. The primers were designed with the appropriate enzyme restriction site followed by a conserved Kozak nucleotide sequence (in most cases(NB except in occasional instances for example ID59) GCCACC was used. The Kozak sequence facilitates the recognition of initiator sequences by eukaryotic ribosomes) and an ATG start codon upstream of the insert of the gene of interest. For example the forward primer using a BamHI site the primer would begin GCGGGATCCGCCACCATG followed by a small section of the 5' end of the gene of interest. The reverse primer was designed to be compatible with the forward primer and with a Notl restriction site at the 5' end in most cases (this site is TTGCGGCCGC) (NB except in occasional instances for example ID59 where a Xhol site was used instead of Notl).

PCR primers

The following PCR primers were designed and used to amplify the truncated genes of interest.

ID5

Forward Primer 5'

CGGATCCGCCACCATGGGTCTAATTGAAGACTTAAAAAATCAA 3 ' Reverse Primer 5' TTGCGGCCGCCAATGCTAGACTAAACACAAGACTCA 3'

ID59

Forward Primer 5' CGCGGATCCATGAAAAAAATCTATTCATTTTTAGCA 3' Reverse Primer 5' CCCTCGAGGGCTACTTCCGATACATTTTAAACTGTAGG 3'

ID51

Forward Primer 5 ' CGGATCCGCCACCATGAGTCATGTCGCTGCAAATG 3 ' Reverse Primer 5' TTGCGGCCGC ATACCAAACGCTGACATCTACG 3' ID29

Forward Primer 5' CGGATCCGCCACCATGCAAAAAGAGCGGTATGGTTATG 3' Reverse Primer 5 ' TTGCGGCCGCACCCCCATTCTTAATCCCTT 3 '

ID50

Forward Primer 5' CGGATCCGCC ACC ATGGAGGT ATGTGA A ATGTC ACGTA A A 3 '

Reverse Primer 5' TTGCGGCCGCTTTTACAAAGTCAAGCAAAGCC 3'

Cloning The insert along with the flanking features described above was amplified using PCR against a template of genomic DNA isolated from type 4 S. pneumoniae strain 11886 obtained from the National Collection of Type Cultures. The PCR product was cut with the appropriate restriction enzymes and cloned in to the multiple cloning site of pcDNA3.1 using conventional molecular biological techniques. Suitably mapped clones of the genes of interested were cultured and the plasmids isolated on a large scale ( > 1.5 mg) using Plasmid Mega Kits (Qiagen). Successful cloning and maintenance of genes was confirmed by restriction mapping and sequencing ~ 700 base pairs through the 5 ' cloning junction of each large scale preparation of each construct.

Strain validation

A strain of type 4 was used in cloning and challenge methods which is the strain from which the S. pneumoniae genome was sequenced. A freeze dried ampoule of a homogeneous laboratory strain of type 4 S. pneumoniae strain NCTC 11886 was obtained from the National Collection of Type Strains. The ampoule was opened and the cultured re suspended with 0.5 ml of tryptic soy broth (0.5% glucose, 5% blood). The suspension was subcultured into 10 ml tryptic soy broth (0.5% glucose, 5% blood) and incubated statically overnight at 37°C. This culture was streaked on to 5 % blood agar plates to check for contaminants and confirm viability and on to blood agar slopes and the rest of the culture was used to make 20% glycerol stocks. The slopes were sent to the Public Health Laboratory Service where the type 4 serotype was confirmed.

A glycerol stock of NCTC 11886 was streaked on a 5 % blood agar plate and incubated overnight in a CO2 gas jar at 37°C. Fresh streaks were made and optochin sensitivity was confirmed. Pneumococcal challenge

A standard inoculum of type 4 S. pneumoniae was prepared and frozen down by passaging a culture of pneumococcus lx through mice, harvesting from the blood of infected animals, and grown up to a predetermined viable count of around 109 cfu/ml in broth before freezing down. The preparation is set out below as per the flow chart. Streak pneumococcal culture and confirm identity

V

Grow over-night culture from 4-5 colonies on plate above

V

Animal passage pneumococcal culture

(i.p. injection of cardiac bleed to harvest)

V

Grow over-night culture from animal passaged pneumococcus

Grow day culture (to pre-determined optical density) from over-night of animal passage and freeze down at -70 °C - This is standard minimum

Thaw one aliquot of standard inoculum to viable count

Use standard inoculum to determine effective dose (called Virulence Testing) All subsequent challenges - use standard inoculum to effective dose

An aliquot of standard inoculum was diluted 500x in PBS and used to inoculate the mice.

Mice were lightly anaesthetised using halothane and then a dose of 1.4 x 105 cfu of pneumococcus was applied to the nose of each mouse. The uptake was facilitated by the normal breathing of the mouse, which was left to recover on its back.

S. pneumoniae Vaccine trials

Vaccine trials in mice were carried out by the administration of DNA to 6 week old CBA/ca mice (Harlan, UK). Mice to be vaccinated were divided into groups of six and each group was immunised with recombinant pcDNA3.1 + plasmid DNA containing a specific target-gene sequence of interest. A total of 100 μg of DNA in Dulbecco's PBS (Sigma) was injected intramuscularly into the tibialis anterior muscle of both legs (50 μl in each leg). A boost was carried using the same procedure 4 weeks later. For comparison, control groups were included in all vaccine trials. These control groups were either unvaccinated animals or those administered with non-recombinant pcDNA3.1 + DNA (sham vaccinated) only, using the same time course described above. 3 weeks after the second immunisation, all mice groups were challenged intra-nasally with a lethal dose of S. pneumoniae serotype 4 (strain NCTC 11886). The number of bacteria administered was monitored by plating serial dilutions of the inoculum on 5% blood agar plates. A problem with intranasal immunisations is that in some mice the inoculum bubbles out of the nostrils, this has been noted in results table and taken account of in calculations. A less obvious problem is that a certain amount of the inoculum for each mouse may be swallowed. It is assumed that this amount will be the same for each mouse and will average out over the course of inoculations. However, the sample sizes that have been used are small and this problem may have significant effects in some experiments. All mice remaining after the challenge were killed 3 or 4 days after infection. During the infection process, challenged mice were monitored for the development of symptoms associated with the onset of S. pneumoniae induced-disease. Typical symptoms in an appropriate order included piloerection, an increasingly hunched posture, discharge from eyes, increased lethargy and reluctance to move. The latter symptoms usually coincided with the development of a moribund state at which stage the mice were culled to prevent further suffering. These mice were deemed to be very close to death, and the time of culling was used to determine a survival time for statistical analysis. Where mice were found dead, the survival time was taken as the last time point when the mouse was monitored alive. Interpretation of Results

A positive result was taken as any DNA sequence that was cloned and used in challenge experiments as described above which gave protection against that challenge. Protection was taken as those DNA sequences that gave statistically significant protection (to a 95% confidence level (p <0.05)) and also those which were marginal or close to significant using Mann- Whitney or which show some protective features for example there were one or more outlying mice or because the time to the first death was prolonged. It is acceptable to allow marginal or nonsignificant results to be considered as potential positives when it is considered that the clarity of some of the results may be clouded by the problems associated with the administration of intranasal infections.

Results

Trials 1-6 (see figure 1)

H

Figure imgf000033_0001

CO z m q c r* m rυ σ>

Figure imgf000033_0002

* - bubbled when dosed so may not have received full inoculum. T - terminated at end of experiment having no symptoms of infection. Numbers in brackets - survival times disregarded assuming incomplete dosing p value 1 refers to significance tests compared to unvaccinated controls

p value 2 refers to significance tests compared to pcDNA3.1 + vaccinated controls

Statistical Analyses.

Trial 1 - None of the other groups had significantly longer survival times than the controls. The survival times of the unvaccinated and pcDNA3.1 control groups were not significantly different. One of the mice from ID5 was an outlying result and the mean survival times for ID5 were extended but not significantly so.

Trial 2 - The group vaccinated with ID59 had significantly longer survival times than the unvaccinated control group.

Trial 5 - The group vaccinated with ID59 again survived for an average of almost 10 hours longer than the controls but the results were not quite statistically significant.

Trial 6 - The group vaccinated with ID51 did not have survival times significantly higher than unvaccinated controls (p= < 36.0), however, there were 2 outlying mice in the vaccinated group.

Vaccine trials 7 and 8 (See figure 2)

Figure imgf000034_0001

* - bubbled when dosed so may not have received full inoculum.

T - terminated at end of experiment having no symptoms of infection. Numbers in brackets - survival times disregarded assuming incomplete dosing p value 1 refers to significance tests compared to unvaccinated controls

Statistical Analyses. Trial 7 - The ID29 vaccinated group showed prolonged times to the first death. T

Trial 8 - The group vaccinated with ID50 survived significantly longer than unvaccinated controls.

SUBSTΓΓUTE SHEET (RULE 26) Appendix I - Oligonucleotide primers

nucSl

Bgl ll Eco RV 5'- cgagatctgatatctcacaaacagataacggcgtaaatag -3'

nucS2

Bgl II Sma I

5'- gaagatcttccccgggatcacaaacagataacggcgtaaatag -3'

nucS3

Bgl ll Eco RV 5'- cgagatctgatatocatcacaaacagataacggcgtaaatag -3'

nucR

Bam HI

5'- cgggatccttatggacctgaatcagcgttgtc -3'

NucSeq 5 ' - ggatgctttgtttcaggtgtatc -3 '

pTREPF

5 ' - catgatatcggtacctcaagctcatatcattgtccggcaatggtgtgggctttttttgttttagcggataa caatttcacac -3 ' pTREPR

5 ' - gcggatcccccgggcttaattaatgtttaaacactagtcgaagatctcgcgaattctcctgtgtgaaatt gttatccgcta -3' pUCF

5'- cgccagggttttcccagtcacgac -3'

VR

5'- tcaggggggcggagcctatg -3'

Vl

5'- tcgtatgttgtgtggaattgtg -3' V2

5'- tccggctcgtatgttgtgtggaattg -3'

TABLE 1 ID4 1200 bp

ATGAGAAATATGTGGGTTGTAATCAAGGAAACCTATCTTCGACATGTCGAGTCATGGAGTTTCTTCTTTATGGTGA TTTCGCCGTTCCTCTTTTTAGGAATCTCTGTAGGAATTGGGCATCTCCAAGGTTCTTCTATGGCTAAAAATAATAA AGTGGCAGTAGTGACAACAGTGCCATCTGTAGCAGAAGGACTGAAGAATGTAAATGGTGTTAACTTCGACTATAA AGACGAAGCAAGTGCCAAAGAAGCAATTAAAGAAGAAAAATTAAAAGGTTATTTGACCATTGATCAAGAAGATA GTGTTCTAAAGGCAGTTTATCATGGCGAAACATCGCTTGAAAATGGAATTAAATTTGAGGTTACAGGTACACTCA ATGAACTGCAAAATCAGCTTAATCGTTCAACTGCTTCCTTGTCTCAAGAGCAGGAAAAACGCTTAGCGCAGACAA TTCAATTCACAGAAAAGATTGATGAAGCCAAGGAAAATAAAAAGTTTATTCAAACAATTGCAGCAGGTGCCTTAG GATTCTTTCTTTATATGATTCTGATTACCTATGCGGGTGTAACAGCTCAGGAAGTTGCCAGTGAAAAAGGCACCAA AATTATGGAAGTCGTTTTTTCTAGCATAAGGGCAAGTCACTATTTCTATGCGCGGATGATGGCTCTGTTTCTAGTG ATTTTAACGCATATTGGGATCTATGTTGTAGGTGGTCTGGCTGCCGTTTTGCTCTTTAAΛGATTTGCCATTCTTGGC TCAGTCTGGTATTTTGGATCACTTGGGAGATGCTATCTCACTGAATACCTTGCTCTTTATTTTGATCAGTCTTTTCA TGTACGTAGTCTTGGCAGCCTTCCTAGGATCTATGGTTTCTCGTCCTGAGGACTCAGGGAAAGCCTTGTCGCCTTT GATGATTTTGATTATGGGTGGTTTTTTTGGAGTGACAGCTCTAGGTGCAGCTGGTGACAATCTCCTCTTGAAGATT GGTTCTTATATTCCCTTTATTΓCGACCTTCTTTATGCCGTTTCGAACGATTAATGACTATGCGGGGGGAGCAGAAG CATGGATTTCACTTGCTATTACAGTGATTTTTGCGGTGGTAGCAACAGGATTTATCGGACGCATGTATGCTAGTCT

CGTTCTTCAAACGGATGATTTAGGGATTTGGAAAACCTTTAAACGTGCCTTATCTTATAAATAG

MRNMWVVIKETYLRHVESWSFFFMVISPFLFLGISVGIGHLQGSSMAKNNKVAVVTTVPSVAEGLKNVNGVNFDYKD EASAKEAIKEEKLKGYLTIDQEDSVLKAVYHGETSLENGIKFEVTGTLNELQNQLNRSTASLSQEQEKRLAQTIQFTEKI DEAKENKKFIQTIAAGALGFFLYMILITYAGVTAQEVASEKGTKIMEVVFSSIRASHYFYARMMALFLVILTHIGIYVVG

GLAAVLLFKDLPFLAQSGILDHLGDAISLNTLLFILISLFMYVVLAAFLGSMVSRPEDSGKALSPLMILIMGGFFGVTALG AAGDNLLLKIGSYIPFISTFFMPFRTINDYAGGAEAWISLAITVIFAVVATGFIGRMYASLVLQTDDLGIWKTFKRALSYK

Z ID5 1125 bp

CCTGGGAAAGTCTTGAAAATTATGATAGAATGGTGGAAGGAAAAATTCAGGAGAGTAGTAGTGACTCAAAATGTT GAAAGTCTTCTCGTATCCATTGTAATCAGTGCATACAATGAAGAAAAATATCTGCCTGGTCTAATTGAAGACTTAA AAAATCAAACCTATCCTAAAGAGGATATTGAAATTCTATTTATAAATGCTATGTCCACAGATGGGACCACAGCTA TCATTCAGCAATTTATAAAGGAAGATACAGAGTTTAACTCAATTAGATTGTATAACAATCCTAAGAAAAATCAAG

CTAGTGGTTTTAACCTGGGAGTTAAACATTCTGTAGGGGACCTTATTTTAAAAATTGATGCTCATTCAAAAGTTAC TGAGACTTTTGTAATGAACAATGTGGCTATTATTCAACAAGGTGAATTTGTCTGTGGGGGGCCTAGACCGACGATT GTCGAAGGAAAAGGAAAATGGGCAGAGACCTTGCATCTTGTTGAGGAAAATATGTTTGGCAGTAGCATTGCCAAT TATCGAAATAGTTCTGAGGATAGATATGTTTCTTCTATTTTTCATGGAATGTATAAACGAGAGGTTTTCCAGAAGG TTGGTTTAGTAAATGAGCAACTTGGCCGAACTGAAGATAATGATATTCATTATAGAATTCGAGAATATGGTTATAA

AATCCGCTATAGCCCAAGTATTCTATCTTATCAGTATATTCGACCAACATTCAAGAAAATGCTGCATCAAAAGTAT TCAAATGGTTTGTGGATTGGCTTGACAAGTCATGTTCAGTTTAAGTGTTTATCATTATTTCACTATGTTCCTTGTTT ATTTGTTTTGAGTCTTGTGTTTAGTCTAGCATTGTTACCGATCACATTCGTATTCATAACTTTACTATTAGGTGCCT ATTTTCTACTTTTGTCATTACTCACTTTGCTGACTTTATTAAAACATAAAAATGGATTTCTAATTGTGATGCCCTTT ATTTTATTTTCCATTCACTTTGCTTATGGCCTTGGGACGATTGTAGGTTTAATTAGAGGATTTAAATGGAAGAAGG

AGTACAAGAGAACAATAATTTATTTGGATAAAATAAGCCAAATAAATCAAAATATGCTATAA

PGKVLKIMIEWW EKFRRVVVTQNVESLLVSIVISAYNEEKYLPGLIEDLKNQTYPKEDIEILFINAMSTDGTTAIIQQFIK EDTEFNSIRLYNNPKKNQASGFNLGVKHSVGDLILKIDAHSKVTETFVMNNVAIIQ GEFVCGGPRPTIVEGKGKWAET LHLVEENMFGSSIANYRNSSEDRYVSSIFHGMYKREVFQKVGLVNEQLGRTEDNDIHYRIREYGYKIRYSPSILSYQYIRP

TFKKMLHQKYSNGLWIG TSHVQFKCLSLFHYVPCLFVLSLVFSLALLPITFVFITLLLGAYFLLLSLLTLLTLLKHKNGF LIVMPFILFSIHFAYGLGTIVGLIRGFKWKKEYKRTIIYLDKISQINQNMLZ

ID11 696 bp

ATGATGAAAGAACAAAATACGATAGAAATCGATGTATTTCAATTAGTTAAAAGCTTGTGGAAACGCAAGCTAATG ATTTTAATAGTGGCACTTGTGACAGGTGCGGGGGCTTTTGCATATAGCACTTTTATTGTTAAGCCAGAATATACGA GTACCACGCGAATTTACGTAGTGAATCGCAATCAAGGAGACAAGCCGGGGTTGACAAATCAGGATTTGCAGGCAG GAACTTATCTGGTAAAAGACTACCGTGAGATTATCCTTTCGCAGGATGTTTTGGAGGAAGTTGTTTCTGATTTGAA ACTAGATTTGACGCCAAAAGGTTTGGCTAATAAAATTAAAGTGACAGTACCAGTTGATACCCGTATTGTCTCTATT

TCAGTTAATGATCGAGTTCCTGAAGAGGCAAGCCGTATCGCTAACTCTTTGAGAGAAGTAGCTGCTCAAAAAATT ATCAGTATTACTCGTGTTTCTGACGTGACAACACTGGAGGAGGCAAGGCCGGCGATATCCCCGTCTTCGCCAAAT ATTAAACGCAATACACTAATTGGTTTTTTGGCAGGGGTGATTGGAACTAGTGTTATAGTTCTTCATCTTGAACTTTT GGATACTCGTGTGAAACGTCCGGAAGATATCGAAAATACATTGCAGATGACACTTTTGGGAGTTGTGCCAAACTT GGGTAAGTTGAAATAG

MMKEQNTIEIDVFQLVKSLWKRKLMILIVALVTGAGAFAYSTFIVKPEYTSTTRIYVVNRNQGDKPGLTNQDLQAGTYL VKDYREIILSQDVLEEVVSDLKLDLTPKGLANKIKVTVPVDTRIVSISVNDRVPEEASRIANSLREVAAQKIISITRVSDVT

T EEARPAISPSSPNIKRNTLIGFLAGVIGTSVIVLHLELLDTRVKRPEDIENTLQMTLLGVVPNLGKLKZ

ID19 555 bp ATGGTAAAAGTAGCAGTTATATTAGCTCAGGGCTTTGAAGAAATTGAAGCCTTGACAGTTGTAGATGTCTTGCGTC

GAGCCAATATCACATGTGATATGGTTGGTTTTGAAGAGCAAGTAACGGGTTCGCATGCAATCCAAGTAAGAGCAG ATCATGTCTTTGATGGAGATTTATCAGACTATGATATGATTGTTCTTCCTGGAGGTATGCCTGGTTCTGCACATTTA CGTGATAATCAGACCTTGATTCAAGAATTGCAAAGCTTCGAGCAAGAAGGGAAGAAACTAGCAGCCATTTGTGCG GCACCAATTGCCCTCAATCAAGCAGAGATATTGAAAAATAAGCGATACACTTGTTATGACGGCGTTCAAGAGCAA ATCCTTGATGGTCACTACGTCAAGGAAACAGTAGTGGTAGATGGTCAGTTGACAACCAGTCGGGGTCCTTCAACA

GCCCTTGCCTTTGCCTACGAGTTGGTGGAGCAACTAGGAGGGGACGCAGAGAGTTTACGAACAGGAATGCTCTAT CGAGATGTCTTTGGTAAAAATCAGTAA

MVKVAVILAQGFEEIEALTVVDVLRRANITCDMVGFEEQVTGSHAIQVRADHVFDGDLSDYDMIVLPGGMPGSAHLR DNQTLIQELQSFEQEGKKLAAICAAPIALNQAEILKNKRYTCYDGVQEQILDGHYVKETVVVDGQLTTSRGPSTALAFA

YELVEQLGGDAESLRTGM YRDVFGKNQZ

ID27 306 bp GTGGTAGGGATGGTAGAACCAAACCTAGAAAGCCTTATAAAAGATCTTTACAATCATGCTCGACATGATTTGAGT

GAAGATTTAGTTGCTGCTCTCCTAGAGACTACTAAAAAACTGCCTACTACAAATGAGCAATTGCAGGCAGTTCGTC TCTCAGGCCTGGTCAATCGTGAATTGCTCCTAAATCCCAAACATCCAGCACCTGAGTTGCTCAACTTGGCTCGCTT TGTCAAAAGAGAAGAAGCCAAGTACAGAGGAACTGCGACTTCTGCGCTTATGTATGAGGAACTCTTTAAAATGCT TTGA

MVGMVEPNLESLIKDLYNHARHDLSEDLVAALLETTKKLPTTNEQLQAVRLSGLVNRELLLNPKHPAPELLNLARFVK REEAKYRGTATSALMYEELFKMLZ

ID29 945 bp

TTGTTCTTAAAAAAGGAAAGAGAGGTAATCAGCATGCGTAAATGGACAAAAGGATTTCTCATCTTTGGTGTGGTG ACTACCGTTATCGGCTTTATCCTGCTTrrTGTAGGTATCCAATCTGACGGGAtTAAGAGCCTACTTTCCATGTCCAA AGAACCTGTCTATGATAGCCGTACGGAAAAGCTAACCTTTGGCAAGGAAGTCGAAAACCTAGAAATTACTCTCCA CCAACACACGCTCACCATCACAGACTCTTTCGATGATCAAATCCACATTTCTTACCATCCATCTCTTTCTGCTCAC CATGATCTTATCACCAATCAGAACGATAGAACTCTGAGTCTCACTGATAAGAAACTGTCTGAAACTCCGTTTCTCT

CTTCTGGAATTGGTGGGATTCTTCATATCGCAAGTAGCTACTCTAGTCGTTTTGAAGAAGTTATTCTCCGACTACC AAAAGGGAGAACTCTAAAAGGGATCAACATCTCAGCCAATCGCGGACAAACCACCATCATAAATGCTAGCCTTGA AAATGCGACCCTCAATACAAACAGCTATATCCTCCGAATTGAAGGAAGTCGTATCAAAAACAGTAAACTCACAAC GCCCAATATCGTTAATATCTTTGATACAGTTCTTACAGATAGTCAGCTAGAGTCAACAGAGAATCACTTCCACGCT GAAAATATCCAAGTCCATGGCAAGGTTGAACTGACTGCCAAAGATTATCTCAGAATCATCCTAGACCAGAAAGAA

AGCCAACGAATTAACTGGGACATCTCAAGCAACTATGGTTCTATCTTCCAATTCACAAGAGAAAAGCCTGAATCA AGAGGTACGGAATTAAGCAACCCTTACAAAACTGAAAAAACCGATGTCAAGGATCAACTCATTGCGAGATCTGAT GATAATATTGATCTAATATCCACACCAAGCAGACGTTGA MFLKKEREVISMRKWTKGFLIFGVVTTVIGFILLFVGIQSDGIKSLLSMSKEPVYDSRTEKLTFGKEVENLEITLHQHTLTI

TDSFDDQIHISYHPSLSAHHDLITNQNDRTLSLTDKKLSETPFLSSGIGGILHIASSYSSRFEEVILRLPKGRTLKGINISANR GQTTIINASLENATLNTNSYILRIEGSRI NSKLTTPNIVNIFDTVLTDSQLESTENHFHAENIQVHGKVELTAKDYLRIILD QKESQRINWDISSNYGSIFQFTREKPESRGTELSNPYKTEKTDVKDQLIARSDDNIDLISTPSRRZ ID30 879 bp

ATGAAACAAGAATGGTTTGAAAGTAATGATTTTGTAAAAACAACAAGCAAGAACAAGCCTGAAGAGCAAGCTCA AGAGGTTGCAGACAAGGCTGAAGAAACGATAGCCGATCTCGATACACCAATTGAAAAAAATACTCAGTTAGAGG AGGAAGTCCCTCAAGCTGAAGTCGAATTGGAAAGCCAGCAAGAAGAGAAAATTGAAGCTCCTGAAGACAGTGAA GCGAGAACAGAAATAGAAGAAAAGAAGGCATCTAATTCTACTGAAGAAGAGCCAGACCTTTCTAAAGAAACAGA

AAAAGTCACTATAGCTGAAGAGAGCCAAGAAGCTCTTCCTCAGCAAAAAGCAACCACGAAAGAGCCACTTCTTAT CAGTAAATCTTTAGAAAGTCCTTATATCCCCGACCAAGCTCCAAAATCTAGGGATAAATGGAAAGAGCAAGTGCT TGATTTTTGGTCTTGGCTAGTGGAAGCGATCAAATCTCCTACAAGTAAGTTGGAAACAAGTATCACACACAGTTAC ACAGCCTTTCTCTTGCTCATTCTGTTTTCTGCATCTTCCTTTTTCTTTAGTATCTATCACATCAAACATGCTTACTAT AGTAGCGACAACACTCTTCTTCTTTTCATTCCTCTTGGGTAGTTTCGTTGTGAGACGATTTATCCACCAGGAAAAG GACTGGACGCTAGACAAGGTTCTCCAACAATATAGTCAACTCTTGGCAATTCCAATCTCCTCACTGCTATTGCTAG TTTCTTTGCTTTCTTTGATAGCCTACGATTTACAGCCCTCTTGTGTGTGA MKQEWFESNDFVKTTSKNKPEEQAQEVADKAEETIADLDTPIEKNTQLEEEVPQAEVELESQQEEKIEAPEDSEARTEIE

EKKASNSTEEEPDLSKETEKVTIAEESQEALPQQKATT EPLLISKSLESPYIPDQAPKSRDKWKEQVLDFWSWLVEAIKS PTSKLETSITHSYTAFLLLILFSASSFFFSIYHIKHAYYGHIASINSRFPEQLAPLTLFSIISILVATTLFFFSFLLGSFVVRRFIH QEKDWTLDKVLQQYSQLLAIPISSLLLLVSLLSLIAYDLQPSCVZ ID105 990 bp

ATGCAACTCGCTTCTTCGGTCTACTCATTGTTCGTCTGGTACAATTTGTTCTTAAAAAAGGAAAGAGAGGTAATCA GCATGCGTAAATGGACAAAAGGATTTCTCATCTTTGGTGTGGTGACTACCGTTATCGGCTTTATCCTGCTTTTTGTA GGTATCCAATCTGACGGGATTAAGAGCCTACTTTCCATGTCCAAAGAACCTGTCTATGATAGCCGTACGGAAAAG CTAACCTTTGGCAAGGAAGTCGAAAACCTAGAAATTACTCTCCACCAACACACGCTCACCATCACAGACTCTTTC

GATGATCAAATCCACATTTCTTACCATCCATCTCTTTCTGCTCACCATGATCTTATCACCAATCAGAACGATAGAA CTCTGAGTCTCACTGATAAGAAACTGTCTGAAACTCCGTTTCTCTCTTCTGGAATTGGTGGGATTCTTCATATCGC AAGTAGCTACTCTAGTCGTTTTGAAGAAGTTATTCTCCGACTACCAAAAGGGAGAACTCTAAAAGGGATCAACAT CTCAGCCAATCGCGGACAAACCACCATCATAAATGCTAGCCTTGAAAATGCGACCCTCAATACAAACAGCTATAT CCTCCGAATTGAAGGAAGTCGTATCAAAAACAGTAAACTCACAACGCCCAATATCGTTAATATCTTTGATACAGTT

CTTACAGATAGTCAGCTAGAGTCAACAGAGAATCACTTCCACGCTGAAAATATCCAAGTCCATGGCAAGGTTGAA CTGACTGCCAAAGATTATCTCAGAATCATCCTAGACCAGAAAGAAAGCCAACGAATTAACTGGGACATCTCAAGC AACTATGGTTCTATCTTCCAATTCACAAGAGAAAAGCCTGAATCAAGAGGTACGGAATTAAGCAACCCTTACAAA ACTGAAAAAACCGATGTCAAGGATCAACTCATTGCGAGATCTGATGATAATATTGATCTAATATCCACACCAAGC AGACGTTGA

MQLASSVYSLFVWYNLFLKKEREVISMRKWTKGFLIFGVVTTVIGFILLFVGIQSDGIKSLLSMSKEPVYDSRTEKLTFG KEVENLEITLHQHTLTITDSFDDQIHISYHPSLSAHHDLITNQNDRTLSLTDKKLSETPFLSSGIGGILHIASSYSSRFEEVIL RLPKGRTLKGINISANRGQTTIINASLENATLNTNSYILRIEGSRIKNSKLTTPNIVNIFDTVLTDSQLESTENHFHAENIQV HGKVE TAKDYLRIILDQKESQRINWDISSNYGSIFQFTREKPESRGTELSNPYKTEKTDVKDQLIARSDDNIDLISTPSRR

Z

ID107 -78bp

ATGATATGTAAAATGAAGCAGGGAGGGAGCAGGGCGTGCTGGGGATGGAGAGTGGGGGAGGGACGCTGCTATTT TAATC

MICKMKQGGSRACWGWRVGEGRCYFN

ID109 714 bp

CGATAAAGAGGCCTTGAGTAATCTCAATTTGCAGATTGAAAATGGAGAGATTATGGGCTTGATTGGTCATAATGG GGCTGGAAAATCGACCACTATAAAATCCCTAGTCAGTATCATTTCACCCAGCAGTGGTCGTATTTTGGTAGACGGT

CAGGAGTTATCGGAAAATCGCTTGGCTATTAAACGAAAGATTGGCTACGTAGCAGACTCGCCTGACTTATTTTTAC GCTTAACGGCCAATGAATTTTGGGAATTGATCGCCTCATCCTATGATCTGAGTAGATCTGACTTGGAGGCTAGTCT AGCTAGGCTATTGAACGTTTTTGATTTTGCTGAAAATCGCTATCAGGTTATTGAAACTCTTTCTCACGGAATGCGT CAGAAAGTCTTTGTCATCGGAGCACTCTTGTCTGATCCCGATATTTGGGTTTTGGACGAACCCTTGACTGGTTTGG ATCCCCAGGCTGCCTTTGATTTGAAACAGATGATGAAGGAACATGCACAAAAAGGGAAGACAGTCTTGTTTTCAA

CTCATGTCCTAGAGGTGGCAGAGCAAGTCTGTGATCGGATTGCCATTTTGAAAAAGGGGCATTTGATTTATTGTGG TAAGGTAGAGGACTTGAGGAAAGACCACCCAGACCAGTCTTTGGAAAGTATCTACCTTAGTCTTGCTGGTAGAAA AGAGGAGGTTGCGGATGCGTCTCAAGGTCATTAA DKEALSNLNLQIENGEIMGLIGHNGAGKSTTIKSLVSIISPSSGRILVDGQELSENRLAIKRKIGYVADSPDLFLRLTANEF

WELIASSYDLSRSDLEASLARLLNVFDFAENRYQVIETLSHGMRQKVFVIGALLSDPDIWVLDEPLTGLDPQAAFDL Q MMKEHAQKGKTVLFSTHVLEVAEQVCDRIAILK GHLIYCGKVEDLRKDHPDQSLESIYLSLAGRKEEVADASQGHZ

ID112 360 bp

ATGGCTTTGTTTTCAGAGAGAGGAGCAGTACGGAAGACACCAATGGCAAGTCCAATAATGAGACCTATGATGGTT CCGACGATAGAGATTAAAAGAGTGATACCAGCACCACGCAAGAGTTGTTGCCAGTTTTCAGAAAGAATTTTAGCA ACTTGGCTAAAGAAACTACTGCTAGTCTCTTCAGTTGTTGTAGCTTCGGCAGGTTGTTCCTTGATCATACGATCCA TCAAGGCAACTTGGTCATCTTTTGAAATGGTTTCAATGCTGGCATTGATTTGGCTAATACGATTGTCATTTTTACGA AGCCCGATAGCGATAGCTGTATCTTCTTCCCCAGTTTTGAAACCAGGTTCTACTTGA

SUBSTΓΓUTE SHEET (RULE 26) MALFSERGAVRKTPMASPIMRPMMVPTIEIKRVIPAPRKSCCQFSERILATWLKKLLLVSSVVVASAGCSLIIRSIKATWSS FEMVSMLALIWLIRLSFLRSPIAIAVSSSPVLKPGSTZ ID 128 - 3.43

ATGAAATTTAGTAAAAAATATATAGCAGCTGGATCAGCTGTTATCGTATC

CTTGAGTCTATGTGCCTATGCACTAAACCAGCATCGTTCGCAGGAAAATA

AGGACAATAATCGTGTCTCTTATGTGGATGGCAGCCAGTCAAGTCAGAAA AGTGAAAACTTGACACCAGACCAGGTTAGCCAGAAAGAAGGAATTCAGGC

TGAGCAAATTGTAATCAAAATTACAGATCAGGGCTATGTAACGTCACACG

GTGACCACTATCATTACTATAATGGGAAAGTTCCTTATGATGCCCTCTTT

AGTGAAGAACTCTTGATGAAGGATCCAAACTATCAACTTAAAGACGCTGA

TATTGTCAATGAAGTCAAGGGTGGTTATATCATCAAGGTCGATGGAAAAT ATTATGTCTACCTGAAAGATGCAGCTCATGCTG ATAATGTTCG AACTAAA

GATGAAATCAATCGTCAAAAACAAGAACATGTCAAAGATAATGAGAAGGT

TAACTCTAATGTTGCTGTAGCAAGGTCTCAGGGACGATATACGACAAATG

ATGGTTATGTCTTTAATCCAGCTGATATTATCGAAGATACGGGTAATGCT

TATATCGTTCCTCATGGAGGTCACTATCACTACATTCCCAAAAGCGATTT ATCTGCTAGTGAATTAGCAGCAGCTAAAGCACATCTGGCTGGAAAAAATA

TGCAACCGAGTCAGTTAAGCTATTCTTCAACAGCTAGTGACAATAACACG

CAATCTGTAGCAAAAGGATCAACTAGCAAGCCAGCAAATAAATCTGAAAA

TCTCCAGAGTCTTTTGAAGGAACTCTATGATTCACCTAGCGCCCAACGTT

ACAGTGAATCAGATGGCCTGGTCTTTGACCCTGCTAAGATTATCAGTCGT ACACCAAATGGAGTTGCGATTCCGCATGGCGACCATTACCACTTTATTCC

TTACAGCAAGCTTTCTGCCTTAGAAGAAAAGATTGCCAGAATGGTGCCTA

TCAGTGGAACTGGTTCTACAGTTTCTACAAATGCAAAACCTAATGAAGTA

GTGTCTAGTCTAGGCAGTCTTTCAAGCAATCCTTCTTCTTTAACGACAAG

TAAGGAGCTCTCTTCAGCATCTGATGGTTATATTTTTAATCCAAAAGATA TCGTTGAAGAAACGGCTACAGCTTATATTGTAAGACATGGTGATCATTTC

CATTACATTCCAAAATCAAATCAAATTGGGCAACCGACTCTTCCAAACAA

TAGTCTAGCAACACCTTCTCCATCTCTTCCAATCAATCCAGGAACTTCAC

ATGAGAAACATGAAGAAGATGGATACGGATTTGATGCTAATCGTATTATC

GCTGAAGATGAATCAGGTTTTGTCATGAGTCACGGAGACCACAATCATTA TTTCTTCAAGAAGGACTTGACAGAAGAGCAAATTAAGGTGCGCAAAAACA

TTTAG

MKFSKKYIAAGSAVIVSLSLCAYALNQHRSQENKDNNRVSYVDGSQSSQK

SENLTPDQVSQKEGIQAEQIVI ITDQGYVTSHGDHYHYYNGKVPYDALF SEELLMKDPNYQLKDADIVNEVKGGYIIKVDGKYYVYLKDAAHADNVRTK

DEINRQKQEHVKDNEKVNSNVAVARSQGRYTTNDGYVFNPADIIEDTGNA

YIVPHGGHYHYIPKSDLSASELAAAKAHLAGKNMQPSQLSYSSTASDNNT

QSVAKGSTSKPANKSENLQSLLKELYDSPSAQRYSESDGLVFDPAKIISR

TPNGVAIPHGDHYHF1PYS LSALEEKIARMVPISGTGSTVSTNAKPNEV VSSLGSLSSNPSSLTTSKE SSASDGYIFNPKDIVEETATAYIVRHGDHF

HYIPKSNQIGQPTLPNNSLATPSPSLPINPGTSHEKHEEDGYGFDANRII

AEDESGFVMSHGDHNHYFFKKDLTEEQIKVRKNI*

SUBSTΓΓUTE SHEET (RULE 26) TABLE 2

ID2 840 bp ATGGGAATTGCTCTAGAAAATGTGAATTTTACATATCAAGAAGGTACTCCCTTAGCTTCAGCAGCTTTGTCGGATG

TTTCTTTGACGATTGAAGATGGCTCTTATACAGCTTTAATTGGGCACACAGGTAGTGGTAAATCAACTATTTTACA ACTCTTAAATGGTTTATTGGTGCCAAGTCAAGGGAGTGTGAGGGTTTTTGATACCTTAATCACCTCGACTTCTAAA AATAAAGATATTCGTCAAATTAGAAAACAGGTTGGCTTGGTATTΓCAGTTTGCTGAAAATCAGATTTTTGAAGAAA CGGTTTTGAAGGACGTTGCTTTTGGACCGCAAAATTTTGGAGTTTCTGAAGAAGATGCTGTGAAGACTGCGCGTGA GAAACTGGCTCTGGTRGGAATTGATGAATCACTTTTTGATCGTAGTCCGTTTGAGCTGTCAGGGGGACAAATGAGA

CGTGTTGCCATTGCAGGCATACTTGCCATGGAGCCAGCTATATTAGTCTTAGATGAGCCAACAGCTGGTCTAGATC CTCTAGGGAGAAAAGAGTTGATGACCCTGTTCAAAAAACTCCACCAGTCAGGGATGACCATCGTCTTGGTAACGC ATTTGATGGATGATGTTGCTGAATATGCGAATCAAGTCTATGTAATGGAAAAGGGACGTTTAGTAAAGGGGGGCA AACCAAGTGATGTCTTTCAAGACGTTGTTTTTATGGAAGAAGTTCAGTTGGGAGTACCTAAAATTACGGCCTTTTG TAAACGATTGGCTGATAGAGGCGTGTCATTTAAACGATTACCGATTAAGATAGAGGAGTTCAAGGAGTCGCTAAA

TGGATAG

MGIALENVNFTYQEGTPLASAALSDVSLTIEDGSYTALIGHTGSGKSTILQLLNGLLVPSQGSVRVFDTLITSTSKNKDIR QIRKQVGLVFQFAENQIFEETVLKDVAFGPQNFGVSEEDAVKTAREKLALVGIDESLFDRSPFELSGGQMRRVAIAGILA MEPAILVLDEPTAGLDPLGR ELMTLFKKLHQSGMTIVLVTHLMDDVAEYANQVYVMEKGRLVKGGKPSDVFQDVV

FMEEVQLGVPKITAFCKRLADRGVSFKRLPIKIEEFKESLNGZ

ID 3 6360 bp TACCCGGTAGTCTTAGCAGACACATCTAGCTCTGAAGATGCTTTAAACATCTCTGATAAAGAAAAAGTAGCAGAA

AATAAAGAGAAACATGAAAATATCCATAGTGCTATGGAAACTTCACAGGATTTTAAAGAGAAGAAAACAGCAGTC ATTAAGGAAAAAGAAGTTGTTAGTAAAAATCCTGTGATAGACAATAACACTAGCAATGAAGAAGCAAAAATCAA AGAAGAAAATTCCAATAAATCCCAAGGAGATTATACGGACTCATTTGTGAATAAAAACACAGAAAATCCCAAAAA AGAAGATAAAGTTGTCTATATTGCTGAATTTAAAGATAAAGAATCTGGAGAAAAAGCAATCAAGGAACTATCCAG TCΓTAAGAATACAAAAGTTTTATATACTTATGATAGAATTTTTAACGGTAGTGCCATAGAAACAACTCCAGATAAC

TTGGACAAAATTAAACAAATAGAAGGTATTTCATCGGTTGAAAGGGCACAAAAAGTCCAACCCATGATGAATCAT GCCAGAAAGGAAATTGGAGTTGAGGAAGCTATTGATTACCTAAAGTCTATCAATGCTCCGTTTGGGAAAAATTTT GATGGTAGAGGTATGGTCATTTCAAATATCGATACTGGAACAGATTATAGACATAAGGCTATGAGAATCGATGAT GATGCCAAAGCCTCAATGAGATTTAAAAAAGAAGACTTAAAAGGCACTGATAAAAATTATTGGTTGAGTGATAAA ATCCCTCATGCGTTCAATTATTATAATGGTGGCAAAATCACTGTAGAAAAATATGATGATGGAAGGGATTATTTTG

ACCCACATGGGATGCATATTGCAGGGATTCTTGCTGGAAATGATACTGAACAAGACATCAAAAACTTTAACGGCA TAGATGGAATTGCACCTAATGCACAAATTTTCTCTTACAAAATGTATTCTGACGCAGGATCTGGGTTTGCGGGTGA TGAAACAATGTTTCATGCTATTGAAGATTCTATCAAACACAACGTTGATGTTGTTTCGGTATCATCTGGTTTTACA GGAACAGGTCTTGTAGGTGAGAAATATTGGCAAGCTATTCGGGCATTAAGAAAAGCAGGCATTCCAATGGTTGTC GCTACGGGTAACTATGCGACTTCTGCTTCAAGTTCTTCATGGGATTTAGTAGCAAATAATCATCTGAAAATGACCG

ACACTGGAAATGTAACACGAACTGCAGCACATGAAGATGCGATAGCGGTCGCTTCTGCTAAAAATCAAACAGTTG AGTTTGATAAAGTTAACATAGGTGGAGAAAGTTTTAAATACAGAAATATAGGGGCCTTTTTCGATAAGAGTAAAA TCACAACAAATGAAGATGGAACAAAAGCTCCTAGTAAATTAAAATTTGTATATATAGGCAAGGGGCAAGACCAAG ATTTGATAGGTTTGGATCTTAGGGGCAAAATTGCAGTAATGGATAGAATTTATACAAAGGATTTAAAAAATGCTTT TAAAAAAGCTATGGATAAGGGTGCACGCGCCATTATGGTTGTAAATACTGTAAATTACTACAATAGAGATAATTG

GACAGAGCTTCCAGCTATGGGATATGAAGCGGATGAAGGTACTAAAAGTCAAGTGTTTTCAATTTCAGGAGATGA TGGTGTAAAGCTATGGAACATGATTAATCCTGATAAAAAAACTGAAGTCAAAAGAAATAATAAAGAAGATTTTAA AGATAAATTGGAGCAATACTATCCAATTGATATGGAAAGTTTTAATTCCAACAAACCGAATGTAGGTGACGAAAA AGAGATTGACTTTAAGTTTGCACCTGACACAGACAAAGAACTCTATAAAGAAGATATCATCGTTCCAGCAGGATC TACATCTTGGGGGCCAAGAATAGATTTACTTTTAAAACCCGATGTTTCAGCACCTGGTAAAAATATTAAATCCACG

CTTAATGTTATTAATGGCAAATCAACTTATGGCTATATGTCAGGAACTAGTATGGCGACTCCAATCGTGGCAGCTT CTACTGTTTTGATTAGACCGAAATTAAAGGAAATGCTTGAAAGACCTGTATTGAAAAATCTTAAGGGAGATGACA AAATAGATCTTACAAGTCTTACAAAAATTGCCCTACAAAATACTGCGCGACCTATGATGGATGCAACTTCTTGGA AAGAAAAAAGTCAATACTTTGCATCACCTAGACAACAGGGAGCAGGCCTAATTAATGTGGCCAATGCTTTGAGAA ATGAAGTTGTAGCAACTTTCAAAAACACTGATTCTAAAGGTTTGGTAAACTCATATGGTTCCATTTCTCTTAAAGA

AATAAAAGGTGATAAAAAATACTTTACAATCAAGCTTCACAATACATCAAACAGACCTTTGACTTTTAAAGTTTCA GCATCAGCGATAACTACAGATTCTCTAACTGACAGATTAAAACTTGATGAAACATATAAAGATGAAAAATCTCCA GATGGTAAGCAAATTGTTCCAGAAATTCACCCAGAAAAAGTCAAAGGAGCAAATATCACATTTGAGCATGATACT TTCACTATAGGCGCAAATTCTAGCTTTGATTTGAATGCGGTTATAAATGTTGGAGAGGCCAAAAACAAAAATAAA TTTGTAGAATCATTTATTCATTTTGAGTCAGTGGAAGCGATGGAAGCTCTAAACTCCAGCGGGAAGAAAATAAAC

TTCCAACCTTCTTTGTCGATGCCTCTAATGGGATTTGCTGGGAATTGGAACCACGAACCAATCCTTGATAAATGGG CTTGGGAAGAAGGGTCAAGATCAAAAACACTGGGAGGTTATGATGATGATGGTAAACCGAAAATTCCAGGAACCT TAAATAAGGGAATTGGTGGAGAACATGGTATAGATAAATTTAATCCAGCAGGAGTTATACAAAATAGAAAAGATA AAAATACAACATCCCTGGATCAAAATCCAGAATTATTTGCTTTCAATAACGAAGGGATCAACGCTCCATCATCAA GTGGTTCTAAGATTGCTAACATTTATCCTTTAGATTCAAATGGAAATCCTCAAGATGCTCAACTTGAAAGAGGATT

SUBSTΓΓUTE SHEET (RULE 26) AACACCTTCTCCACTTGTATTAAGAAGTGCAGAAGAAGGATTGATTTCAATAGTAAATACAAATAAAGAGGGAGA AAATCAAAGAGACTTAAAAGTCATTTCGAGAGAACACTTTATTAGAGGAATTTTAAATTCTAAAAGCAATGATGC AAAGGGAATCAAATCATCTAAACTAAAAGTTTGGGGTGACTTGAAGTGGGATGGACTCATCTATAATCCTAGAGG TAGAGAAGAAAATGCACCAGAAAGTAAGGATAATCAAGATCCTGCTACTAAGATAAGAGGTCAATTTGAACCGAT TGCGGAAGGTCAATATTTCTATAAATTTAAATATAGATTAACTAAAGATTACCCATGGCAGGTTTCCTATATTCCT

GTAAAAATTGATAACACCGCCCCTAAGATTGTTTCGGTTGATTTTTCAAATCCTGAAAAAATTAAGTTGATTACAA AGGATACTTATCATAAGGTAAAAGATCAGTATAAGAATGAAACGCTATTTGCGAGAGATCAAAAAGAACATCCTG AAAAATTTGACGAGATTGCGAACGAAGTTTGGTATGCTGGCGCCGCTCTTGTTAATGAAGATGGAGAGGTTGAAA AAAATCTTGAAGTAACTTACGCAGGTGAGGGTCAAGGAAGAAATAGAAAACTTGATAAAGACGGAAATACCATTT ATGAAATTAAAGGTGCGGGAGATTTAAGGGGAAAAATCATTGAAGTCATTGCATTAGATGGTTCTAGCAATTTCA

CAAAGATTCATAGAATTAAATTTGCTAATCAGGCTGATGAAAAGGGGATGATTTCCTATTATCTAGTAGATCCTGA TCAAGATTCATCTAAATATCAAAAGCTTGGCGAGATTGCAGAATCTAAATTTAAAAATTTAGGAAATGGAAAAGA GGGTAGTCTAAAAAAAGATACAACTGGGGTAGAACATCATCATCAAGAAAATGAAGAGTCTATTAAAGAAAAAT CTAGTTTTACTATTGATAGAAATATTTCAACAATTAGAGACTTTGAAAATAAAGACTTAAAGAAACTCATTAAAAA GAAATTTAGAGAAGTTGATGATTTTACAAGTGAAACTGGTAAGAGAATGGAGGAATACGATTATAAATACGATGA

TAAAGGAAATATAATAGCCTACGATGATGGGACTGATCTAGAATATGAAACTGAGAAACTTGACGAAATCAAATC AAAAATTTATGGTGTTCTAAGTCCGTCTAAAGATGGACACTTTGAAATTCTTGGAAAGATAAGTAATGTTTCTAAA AATGCCAAGGTATATTATGGGAATAACTATAAATCTATAGAAATCAAAGCGACCAAGTATGATTTCCACTCAAAA ACGATGACATTTGATCTATACGCTAATATTAATGATATTGTGGATGGATTAGCTTTTGCAGGAGATATGAGATTAT TTGTTAAAGATAATGATCAGAAAAAAGCTGAAATTAAAATTAGAATGCCTGAAAAAATTAAGGAAACTAAATCAG

AATATCCCTATGTATCAAGTTATGGGAATGTCATAGAATTAGGGGAAGGAGATCTTTCAAAAAACAAACCAGACA ATTTAACTAAAATGGAATCTGGTAAAATCTATTCTGATTCAGAAAAACAACAATATCTGTTAAAGGATAATATCAT TCTAAGAAAAGGCTATGCACTAAAAGTGACTACCTATAATCCTGGAAAAACGGATATGTTAGAAGGAAATGGAGT CTATAGCAAGGAAGATATAGCAAAAATACAAAAGGCCAATCCTAATCTAAGAGCCCTTTCAGAAACAACAATTTA TGCTGATAGTAGAAATGTTGAAGATGGAAGAAGTACCCAATCTGTATTAATGTCGGCTTTGGACGGCTTTAACATT

ATAAGGTATCAAGTGTTTACATTTAAAATGAACGATAAAGGGGAAGCTATCGATAAAGACGGAAATCTTGTGACA GATRCTTCTAAACTTGTATTATTTGGTAAGGATGATAAAGAATACACTGGAGAGGATAAGTTCAATGTAGAAGCTA TAAAAGAAGATGGCTCCATGTTATTTATTGATACCAAACCAGTAAACCTTTCAATGGATAAGAACTACTTTAATCC ATCTAAATCTAATAAAATTTATGTACGAAATCCAGAATTTTAΓΠ'AAGAGGTAAGATTTCTGATAAGGGTGGTTTT AACTGGGAATTGAGAGTTAATGAATCGGTTGTAGATAATTATΓTAATCTACGGAGATTTACACATTGATAACACTA

GAGATTTTAATATTAAGCTGAATGTTAAAGACGGTGACATCATGGACTGGGGAATGAAAGACTATAAAGCAAACG GATTTCCAGATAAGGTAACAGATATGGATGGAAATGTTTATCTTCAAACTGGCTATAGCGATTTGAATGCTAAAGC AGTTGGAGTCCACTATCAGTTTTTATATGATAATGTTAAACCCGAAGTAAACATTGATCCTAAGGGAAATACTAGT ATCGAATATGCTGATGGAAAATCTGTAGTCTTTAACATCAATGATAAAAGAAATAATGGATTCGATGGTGAGATT CAAGAACAACATATTTATATAAATGGAAAAGAATATACATCATTTAATGATATTAAACAAATAATAGACAAGACA

CTAAACATTAAGATTGTTGTAAAAGATTTTGCAAGAAATACAACCGTAAAAGAATTCATTTTAAATAAAGATACG GGAGAGGTAAGTGAATTAAAACCTCATAGGGTAACTGTGACCATTCAAAATGGAAAAGAAATGAGTTCAACGATA GTGTCGGAAGAAGATTTTATTTTACCTGTTTATAAGGGTGAATTAGAAAAAGGATACCAATTTGATGGTTGGGAAA TTTCTGGTTTCGAAGGTAAAAAAGACGCTGGCTATGTTATTAATCTATCAAAAGATACCTTTATAAAACCTGTATT CAAGAAAATAGAGGAGAAAAAGGAGGAAGAAAATAAACCTACTTTTGATGTATCGAAAAAGAAAGATAACCCAC AAGTAAACCATAGTCAATΓAAATGAAAGTCACAGAAAAGAGGATTTACAAAGAGAAGAGCATTCACAAAAATCT GATTCAACTAAGGATGTTACAGCTACAGTTCTTGATAAAAACAATATCAGTAGTAAATCAACTACTAACAATCCT AATAAGTTGCCAAAAACTGGAACAGCAAGCGGAGCCCAGACACTATTAGCTGCCGGAATAATGTTTATAGTAGGA ATTTTTCTTGGATTGAAGAAAAAAAATCAAGATTAA

YPVVLADTSSSEDALNISDKEKVAENKEKHENIHSAMETSQDFKEKKTAVIKEKEVVSKNPVIDNNTSNEEAKIKEENSN KSQGDYTDSFVNKNTENPKKEDKVVYIAEFKD ESGEKAIKELSSLKNTKVLYTYDRIFNGSAIETTPDNLDKI QIEGIS SVERAQKVQPMMNHARKEIGVEEAIDYLKSINAPFGKNFDGRGMVISNIDTGTDYRH AMRIDDDAKASMRFKKEDL KGTDKNYWLSDKIPHAFNYYNGGKITVEKYDDGRDYFDPHGMHIAGILAGNDTEQDIKNFNGIDGIAPNAQIFSYKMY SDAGSGFAGDET FHAIEDSIKHNVDVVSVSSGFTGTGLVGEKYWQAIRALRKAGIPMVVATGNYATSASSSSWDLVA

NNHLKMTDTGNVTRTAAHEDAIAVASAKNQTVEFDKVNIGGESFKYRNIGAFFDKSKITTNEDGTKAPS LKFVYIGK GQDQDLIGLDLRGKIAVMDRIYTKDLKNAFKKAMDKGARAIMVVNTVNYYNRDNWTELPAMGYEADEGTKSQVFSI SGDDGVKLWNMINPDKKTEVKRNN EDFKDKLEQYYPIDMESFNSNKPNVGDEKEIDFKFAPDTDKELYKEDIIVPAG STSWGPRIDLLLKPDVSAPGKNIKSTLNVINGKSTYGYMSGTSMATPIVAASTVLIRPKLKEMLERPVL NLKGDDKIDL TSLTKIALQNTARPMMDATSWKEKSQYFASPRQQGAGLINVANALRNEVVATFKNTDSKGLVNSYGSISLKEI GDKK

YFTI LHNTSNRPLTFKVSASAITTDSLTDRLKLDETYKDEKSPDGKQIVPEIHPE VKGANITFEHDTFTIGANSSFDLN AVINVGEAKN N FVESFIHFESVEAMEALNSSGKKINFQPSLSMPLMGFAGNWNHEPILDKWAWEEGSRSKTLGGYD DDGKPKIPGTLNKGIGGEHGIDKFNPAGVIQNRKDKNTTSLDQNPELFAFNNEGINAPSSSGSKIANIYPLDSNGNPQDA QLERGLTPSPLVLRSAEEGLISIVNTNKEGENQRDLKVISREHFIRGILNSKSNDAKGIKSSK KVWGDLKWDGLIYNPRG REENAPESKDNQDPATKIRGQFEPIAEGQYFYKFKYRLTKDYPWQVSYIPVKIDNTAPKIVSVDFSNPEKIKLITKDTYHK

VKDQYKNETLFARDQKEHPEKFDEIANEVWYAGAALVNEDGEVEKNLEVTYAGEGQGRNRKLDKDGNTIYEIKGAG DLRGKIIEVIALDGSSNFT IHRIKFANQADEKGMISYYLVDPDQDSSKYQKLGEIAESKFKNLGNGKEGSLKKDTTGVE HHHQENEESIKEKSSFTIDRNISTIRDFENKDLKKLIKKKFREVDDFTSETGKRMEEYDYKYDDKGNIIAYDDGTDLEYE TEKLDEIKS IYGVLSPSKDGHFEILGKISNVSKNAKVYYGNNYKSIEI AT YDFHSKTMTFDLYANINDIVDGLAFAG DMRLFVKDNDQKKAEIKIRMPEKIKETKSEYPYVSSYGNVIELGEGDLSKNKPDNLTKMESGKIYSDSEKQQYLL DNII

SUBSTΓΓUTE SHEET (RULE 26) LRKGYALKVTTYNPGKTDMLEGNGVYSKEDIAKIQKANPNLRALSETTIYADSRNVEDGRSTQSVLMSALDGFNIIRYQ VFTFKMNDKGEAIDKDGNLVTDSSKLVLFGKDD EYTGEDKFNVEAIKEDGSMLFIDTKPVNLSMDKNYFNPS SNKI YVRNPEFYLRGKISDKGGFNWELRVNESVVDNYLIYGDLHIDNTRDFNIKLNVKDGDIMDWGMKDYKANGFPDKVTD MDGNVYLQTGYSDLNA AVGVHYQFLYDNVKPEVNIDPKGNTSIEYADGKSVVFNINDKRNNGFDGEIQEQHIYINGK EYTSFNDIKQIIDKTLNIKIVVKDFARNTTVKEFILNKDTGEVSELKPHRVTVTIQNGKEMSSTIVSEEDFILPVYKGELEK

GYQFDGWEISGFEGKKDAGYVINLSKDTFIKPVFKKIEEKKEEENKPTFDVSKKKDNPQVNHSQLNESHRKEDLQREEH SQKSDSTKDVTATVLDKNNISSKSTTNNPN LPKTGTASGAQTLLAAGI FIVGIFLGLKKKNQDZ

ID6 597 bp

CTTGAATTAAATAAAAAACGTCATGCGACTAAGCATTTTACTGATAAGCTTGTTGATCCCAAAGATGTGCGTACGG CTATCGAAATTGCAACCTTAGCGCCAAGCGCCCACAACAGCCAGCCTTGGAAATTTGTGGTGGTACGTGAGAAAA ATGCTGAACTGGCAAAGTTAGCTTATGGTTCCAATTTTGAACAGGTATCATCAGCGCCTGTAACCATTGCCTTGTT TACAGATACGGACTTAGCCAAACGTGCTCGTAAGATΓGCCCGTGTTGGTGGTGCTAATAACTTTTCTGAAGAGCAA CTTCAATATTTTATGAAAAATCTGCCAGCTGAGTTTGCCCGTTACAGTGAGCAACAAGTCAGCGACTACCTAGCTC

TCAATGCAGGTTΓGGTTGCCATGAACTTGGTTCTTGCATTGACAGACCAAGGAATTGGTTCTAACATTATTCTTGG TTTTGACAAATCAAAAGTTAATGAAGTTTTGGAAATCGAAGACCGTTTCCGCCCAGAACTCTTGATCACAGTGGGT TATACAGACGAAAAATTGGAACCAAGCTACCGCTTGCCAGTAGATGAAATCATCGAGAAAAGATAG LELNKKRHATKHFTDKLVDPKDVRTAIEIATLAPSAHNSQPWKFVVVREKNAELAKLAYGSNFEQVSSAPVTIALFTDT DLAKRARKIARVGGANNFSEEQLQYFMKNLPAEFARYSEQQVSDYLALNAGLVAMNLVLALTDQGIGSNIILGFDKSK VNEVLEIEDRFRPELLITVGYTDEKLEPSYRLPVDEIIEKRZ

ID7 1401 bp

ATGACAGCAATTGATTTTACAGCAGAAGTAGAAAAACGCAAAGAAGACCTCTTGGCTGACTTGTTTAGCCTTTTG GAAATCAATTCAGAACGTGATGACAGCAAGGCTGATGCCCAGCATCCATTTGGGCCTGGTCCAGTAAAAGCCTTG GAGAAATTCCTTGAAATCGCAGACCGCGATGGCTACCCAACTAAGAATGTTGATAACTATGCAGGACATTTTGAG TTTGGTGATGGAGAAGAAGTTCTCGGAATCTTTGCCCATATGGATGTGGTGCCTGCTGGTAGCGGTTGGGACACAG ACCCTTACACACCAACTATCAAAGATGGTCGCCTTTATGCGCGCGGGGCTTCGGACGATAAGGGTCCTACAACAG CTTGTTACTATGGTTTGAAAATCATCAAAGAATTGGGTCTTCCAACTTCTAAGAAAGTTCGCTTCATCGTTGGAAC AGACGAAGAATCAGGCTGGGCAGACATGGACTACTACTTTGAGCACGTAGGACTTGCCAAACCAGATTTCGGTTT CTCACCAGATGCTGAATTTCCAATCATCAATGGTGAAAAAGGAAATATCACGGAATACCTCCACTTTGCAGGAGA AAATACAGGTGTTGCCCGTCTTCACAGCTTTACAGGTGGTTTACGTGAAAATATGGTACCAGAATCAGCAACAGC AGTCGTTTCAGGTGACTTGGCTGACTTGCAAGCTAAACTAGATGCCTTTGTTGCAGAACACAAACTTAGAGGAGA

ACTCCAAGAAGAAGCTGGCAAATACAAGGTGACGATCATTGGTAAATCAGCCCACGGTGCTATGCCTGCTTCAGG TGTCAATGGCGCAACTTACCTTGCCCTCTTCCTCAGCCAGTTTGGCTTTGCTGGTCCAGCCAAAGACTACCTTGAC ATCGCAGGTAAAATTCTCTTGAACGATCATGAGGGTGAAAATCTTAAGATTGCTCATGTGGATGAAAAGATGGGT GCTCΓTTCTATGAATGCCGGCGTCTTCCACTTCGATGAAACAAGTGCTGATAATACCATTGCCCTCAACATCCGCT ATCCAAAAGGAACAAGTCCAGAACAAATCAAGTCAATCCTTGAAAACTTGCCAGTTGTTTCTGTTAGCCTGTCTGA

ACACGGTCACACGCCTCACTATGTGCCAATGGAAGATCCACTTGTGCAAACCTTGTTGAATATCTATGAAAAACA AACTGGCTTTAAAGGTCATGAACAAGTCATCGGTGGTGGAACCTTTGGTCGCTTGCTAGAACGCGGAGTTGCCTA CGGTGCTATGTTCCCAGACTCGATTGATACCATGCACCAAGCCAATGAATTTATCGCCTTGGATGATCTTTTCCGA GCAGCAGCAATTTATGCCGAAGCTATTTACGAATTGATCAAATAA

MTAIDFTAEVEKRKEDLLADLFSLLEINSERDDSKADAQHPFGPGPVKALEKFLEIADRDGYPTKNVDNYAGHFEFGD GEEVLGIFAHMDWPAGSGWDTDPYTPTIKDGRLYARGASDDKGPTTACYYGL Π ELGLPTSKKVRFIVGTDEESGW ADMDYYFEHVGLAKPDFGFSPDAEFPIINGEKGNITEYLHFAGENTGVARLHSFTGGLRENMVPESATAVVSGDLADL QAKLDAFVAEHKLRGELQEEAG Y VTIIGKSAHGAMPASGVNGATY ALFLSQFGFAGPAKDYLDIAGKILLNDHEG ENLKIAHVDEKMGALSMNAGVFHFDETSADNTIALNIRYPKGTSPEQIKSILENLPVVSVSLSEHGHTPHYVPMEDPLVQ

TLLNIYEKQTGFKGHEQVIGGGTFGRLLERGVAYGAMFPDSIDTMHQANEFIALDDLFRAAAIYAEAIYELIKZ

ID8 1617 bp GTGTATACTATTATAAAATCAAATATAAAAAAATTTAGTTTATTAACGATATTTATTGTTGCTGGTCAATTATTGCT

AATTTATGCAGCAACTATTAATGCTCTGGTGTTGAATGAATTAATTGCGATGAATTTAGAGCGGTTTTTGAAATTG TCAATCTACCAAATGATTGTCTGGTGTGGGATAATATTCCTTGACTGGGTAGTGAAAAATTATCAGGTTGAAGTGA TCCAAGAGTTTAATCTAGAGATTCGAAATAGAGTTGCCACAGACATCTCTAACTCTACCTATCAAGAATTTCATAG TAAATCATCAGGAACATATCTTrCGTGGCTAAATAATGATGTTCAGACTTTAAATGATCAGGCGTTTAAACAACTT TTTrTAGTAATAAAAGGAATTTCTGGTACTATATTTGCAGTTGTGACTCTTAATCACTATCATTGGTCATTGACTGT

AGCCACCTTGTTTTCATTAATGATTATGCTACTTGTACCAAAAATCTTTGCATCGAAAATGCGAGAAGTTAGTCTA AATTTAACTAACCAAAATGAAGCTTTTTTAAAATCTAGTGAGACTATATTGAATGGATTTGATGTGTTAGCGTCCT TGAATCTTTTATATGTATTGCCTAAGAAAATTAAAGAAGCAGGAATTTTATTAAAGATGGTTATACAAAGAAAGA CAACTGTAGAAACGTTAGCAGGCGCTATTAGCTTCTTTCTCAATATTTTTTTTCAGATATCTCTCGTTTTTTTAACA GGCTATCTTGCAATAAAAGGAATAGTGAAAATTGGTACTATTGAAGCAATAGGAGCACTAACAGGTGTTATTTTT

SUBSTΓΠΠΈ SHEET (RULE 26) ACAGCGCTAGGTGAATTAGGAGGTCAATTATCCTCTATTATTGGTACGAAGCCTATTTTTTTAAAATTGTATTCAA TTAATCCAATTGAGTCAAATAAAATGAATGATATCGAACCAAATGAGGTGAATAGAGATTTTCCGTTATATGAAG CAAAAAATATTTGCTATAAGTATGGAGATAAAGAAATATTAAAAAACTTAAATTTTTGTTTTCAACGTAATGAAAA GTATTTAATTTTAGGTGAAAGTGGAAGCGGGAAATCTACATTATTAAAATTATTGAATGGCTTTTTGAGAGATTAT AGTGGAGAATTGCGATTCTGCGGGGATGATATAAAAAAAACCTCCTATTTAAATATGGTTTCGAATGTTCTATATG

TAGATCAAAAAGCTTATTTGTTTGAAGGTACGATTAGAGATAATATTTTATTGGAAGAAAATTATACTGATGAAGA AATACTACAGTCTTTAGAGCAAGTTGGTTTGAGTGTAAAAGATTTTCCTAATAACATTTTAGATTATTATGTTGGT GATGATGGGAGATTACTGTCAGGAGGGCAGAAACAAAAAATTACTTTAGCTAGAGGGCTAATTAGAAATAAGAA AATAGTATTAATTGACGAGGGAACTTCTGCTATCGATAGGAGAACTTCGTTAGCGATTGAACGTAAGATATTAGA TAGAGAGGATT GACTGTCATTATTGTTACCCATGCTCCGCATCCGGAACTΓAAACAATATTTTACTAAGATATAT

CAATTTCCAAAGGATTTTATTTAA

MYTΠKSNIKKFSLLTIFIVAGQLLLIYAATINALVLNELIAMNLERFLKLSIYQMIVWCGΠFLDWVVKNYQVEVIQEFNL EIRNRVATDISNSTYQEFHSKSSGTYLSWLNNDVQTLNDQAFKQLFLVIKGISGTIFAVVTLNHYHWSLTVATLFSLMIM LLVPKIFASKMREVSLNLTNQNEAFLKSSETILNGFDVLASLNLLYVLPKKIKEAGILLKMVIQRKTTVETLAGAISFFLNI

FFQISLVFLTGYLAIKGIVKIGTIEAIGALTGVIFTALGELGGQLSSIIGTKPIFLKLYSINPIESNKMNDIEPNEVNRDFPLYE AKNICYKYGD EILKNLNFCFQRNEKYLILGESGSGKSTLLKLLNGFLRDYSGELRFCGDDIKKTSYLNMVSNVLYVDQ KAYLFEGTIRDNILLEENYTDEEILQSLEQVGLSVKDFPNNILDYYVGDDGRLLSGGQKQKITLARG IRNKKIVLIDEGT SAIDRRTSLAIERKILDREDLTVIIVTHAPHPELKQYFTKIYQFPKDFIZ

ID9 705 bp

ATAACAGTTAAACAGATTATGGACGAAATAGCCGTTTCAGATATGACTGCAAGGCGCTATTTACAGGAATTAGCT GATAAAGATTTGCTGATTCGTGTGCATGGTGGAGCTGAAAAACTTCGAACCAACTCCCTTTTGACTAATGAGCGAT CAAATATTGAAAAACAAGCCCTCCAAACGGCAGAAAAACAAGAAATAGCCCATTTTGCAGGCAGTCTAGTAGAA

GAAAGAGAAACTATTTTCATTGGACCAGGAACAACATTAGAGTTΓΓTTGCGCGTGAGTTGCCTATTGACAATATCC GCGTCGTAACCAACAGTCTACCTGTTTTTCTGATTTTAAGCGAACGAAAATTAACAGATΓTGATTTTAATAGGTGG AAATTATCGCGATATTACAGGTGCTTTΓGTTGGTACATTGACCCTACAAAATCTCTCTAATCTCCAATTTTCTAAA GCTTTCGTTAGCTGTAATGGTATTCAAAACGGAGCTCTAGCTACTTTTAGCGAGGAAGAGGGAGAGGCTCAACGC ATCGCTTTAAATAATTCTAATAAAAAATATTTACTCGCAGATCATAGCAAGTTCAATAAGTI GATTTTTATACITT

TTATAATGTATCAAATCTTGATACTATTGRRTCAGATTCTAAACTAAGTGATTCAATCCTTTTTAAGCTATCTAAAC ACATTAAAGTCATCAAGCCTTAA

ITVKQIMDEIAVSDMTARRYLQELADKDLLIRVHGGAEKLRTNSLLTNERSNIEKQALQTAEKQEIAHFAGSLVEERETI FIGPGTTLEFFARELPIDNIRVVTNSLPVFLILSERKLTDLILIGGNYRDITGAFVGTLTLQNLSNLQFSKAFVSCNGIQNGA

LATFSEEEGEAQRIALNNSNKKYLLADHSKFNKFDFYTFYNVSNLDTIVSDSKLSDSILFKLSKHI VIKPZ

ID10 483 bp ATGACTGAGTTTTCGTTAGATCTTCTTCTAGAAGCCATTAAACTAGCTCGTTGGACCTACTACTATCACTTGAAAC

AGCTAGACAAAACAGATAAAGACCAAGAGCTTAAAACTGAAATTCAATCCATCTTTATCGAACACAAGGGAAATT ATGCTTATCGCCGGGTTCATTTAGAACTAAGAAATCGTGGTTATCTGGTAAATCATAAAAGAGTTCAAGGCTTGaT GAAAGTACTCAATTTACAAGCTAAAATGCGAAAGAAACGAAAATATTCTTCTCATAAAGGAGACGTTGGTAAGAA GGCAGAGAATCTCATTCAAGCCCAATTTGAAGGCTCTAAAACAATGGAAAAGTGCTACACAGATGTGACTGAATT TGCCATTCCAGCAAGTACTCAAAAGCTTTACTTATCACCAGTTTTAGATGGCTTTAACAGCGAAATTATTGCTTTT

AATCTTTCTTGTTCGCCTAATTTAGAATAA

MTEFSLDLLLEAIKLARWTYYYHLKQLDKTDKDQELKTEIQSIFIEHKGNYAYRRVHLELRNRGYLVNHKRVQGLMK VLNLQA MRKKRKYSSHKGDVGKKAENLIQAQFEGSKTMEKCYTDVTEFAIPASTQKLYLSPVLDGFNSEIIAFNLSCS PNLEZ

ID14 1266 bp

CCAGGATTTGGTACCGTTGCAAGTGGTGTGCCTTTCCTCCTAAAGGAAAATGGAGGAAAAATCAATCAATCAGCA CATTCAGATATCAAAGTTGCTAAGGTATTGGTCAAGGATGAAGATGAAAAAAATCGCTTGCTTGCAGCAGGGAAT

GACTTTAACTTTGTAACCAATGTGGATGATATTTTATCAGACCAGGATATTACTATCGTAGTGGAATTGATGGGGC GTATTGAGCCTGCTAAAACCTTTATCACTCGTGCCTTGGAAGCTGGAAAACACGTTGTTACTGCTAACAAGGACCT TTTAGCTGTCCATGGCGCAGAATTGCTAGAAATCGCTCAAGCTAACAAGGTAGCACTTTACTACGAAGCAGCAGT TGCTGGTGGGArrCCAATTCTTCGTACTTTAGCAAATTCCTTGGCTTCTGATAAAATTACGCGCGTGCTTGGAGTA GTCAACGGAACTTCCAACTTCATGGTGACCAAGATGGTGGAAGAAGGCTGGTCTTACGATGATGCTCTTGCGGAA

GCACAACGTCTAGGATTTGCAGAAAGCGATCCGACGAATGACGTAGATGGGATTGATGCAGCCTACAAGATGGTT ATTTTGAGCCAATTTGCCTTTGGCATGAAGATTGCCTTTGATGATGTAGCCCACAAGGGAATCCGCAATATCACAC CAGAAGACGTAGCTGTAGCTCAAGAGCTTGGTTACGTAGTGAAATTGGTTGGTTCTATTGAGGAAACTTCTTCAGG TATTGCTGCAGAAGTGACTCCAACCTTCCTACCTAAAGCGCACCCACTTGCTAGTGTGAATGGCGTAATGAACGCT GTCTTTGTAGAATCTATCGGTATTGGTGAGTCTATGTACTACGGACCAGGTGCGGGTCAAAAACCAACTGCAACA

SUBSTΓTUTE SHEET (RULE 26) AGTGTTGTAGCTGATATTGTCCGTATCGTTCGTCGTTTGAATGATGGTACTATTGGCAAAGACTTCAACGAATATA GCCGTGACTTGGTCTTGGCAAATCCTGAAGATGTCAAAGCAAACTACTATTTCTCAATCTTGGCTCTAGACTCAAA AGGTCAGGTCTTGAAGTTGGCTGAAATCTTCAATGCTCAAGATATTTCCTTTAAGCAAATCCTTCAAGATGGCAAA GAGGGTGACAAGGCGCGTGTCGTTATCATCACACACAAGATTAATAAAGCCCAGCTTGAAAATGTCTCAGCTGAA TTGAAGAAGGTTTCAGAATTCGACCTCTTGAATACCTrCAAGGTGCTAGGAGAATAA

PGFGTVASGVPFLLKENGGKINQSAHSDIKVAKVLVKDEDEKNRLLAAGNDFNFVTNVDDILSDQDITIVVELMGRIEP AKTFITRALEAGKHVVTANKDLLAVHGAELLEIAQAN VALYYEAAVAGGIPILRTLANSLASDKITRVLGVVNGTSNF MVTKMVEEGWSYDDALAEAQRLGFAESDPTNDVDGIDAAYKMVILSQFAFGMKIAFDDVAHKGIRNITPEDVAVAQE LGYVVKLVGSIEETSSGIAAEVTPTFLPKAHPLASVNGVMNAVFVESIGIGESMYYGPGAGQKPTATSVVADIVRIVRRL

NDGTIGKDFNEYSRDLVLANPEDV ANYYFSILALDSKGQVLKLAEIFNAQDISFKQILQDG EGDKARVVIITHKINKA QLENVSAELKKVSEFDLLNTFKVLGEZ

ID16 1725 bp

ATGAAACACCTATTATCTTACTTCAAACCCTACATCAAGGAATCAATTTTAGCCCCCTTGTTCAAGCTGTTAGAAG CTGTTTTTGAGCTCTTGGTTCCCATGGTGATTGCTGGGATTGTTGACCAATCTTTACCTCAGGGAGATCAAGGTCA TCTCTGGATGCAGATTGGCCTGCTCCTTATCTTTGCAGTAATTGGCGTTTTAGTGGCCTTGATAGCTCAATTTTACT CAGCAAAGGCAGCAGTAGGTTCTGCTAAGGAATTGACAAACGATCTTTATCGTCATATTCTTTCCTTGCCCAAGGA CAGCAGAGACCGTCTGACAACTTCTAGTTTGGTCACTCGCTTGACTTCGGATACCTACCAGATTCAGACTGGTATC

AATCAATTCCTGCGTCTCTTTTTACGAGCGCCCATTATCGTTTTTGGTGCCATTTTTATGGCTTATCGAATCTCAGC TGAGTTGACTTTCTGGTTCTTAGTCTTGGTTGCCATTTTGACCATTGTCATTGTAGGGTTATCTCGATTGGTCAATC CTTTCTACAGTAGTCTCAGAAAGAAAACGGACCAACTGGTTCAGGAAACGCGCCAGCAATTGCAAGGGATGCGGG TTATTCGTGCTTTTGGTCAAGAAAAACGAGAGTTACAGATTTTTCAAACCCTTAACCAAGTTTATGCTAGATTACA AGAAAAGACAGGTTTCTGGTCTAGTTTATTAACACCTCTGACCTATCTGATTGTCAATGGAACTCTTCTCGTTATT

ATCTGGCAAGGCTATATTTCAATTCAAGGAGGAGTGCTCAGTCAAGGTGCTCTCATTGCTCTTATCAATTACCTCT TACAGATTTTGGTGGAATTGGTCAAGCTAGCCATGTTGATCAATTCCCTCAACCAGTCCTATATCTCAGTCAAGCG AATCGAGGAAGTCTTTGTTGAGGCTCCAGAGGATATCCATTCAGAGTTAGAACAAAAGCAAGCTACCAGAGATAA GGTTTTACAAGTCCAAGAATTGACCTTTACCTATCCTGATGCGGCCCAGCCTTCTCTGAGATACATTTCCTTTGAT ATGACTCAAGGACAAATTCTAGGTATCATCGGGGGAACTGGTTCTGGTAAATCAAGCTTGGTGCAACTCTTACTTG

GACTTTATCCAGTAGACAAGGGGAACATTGACCTTTATCAAAATGGACGTAGTCCTCTTAATTTGGAGCAGTGGC GGTCTTGGATTGCCTATGTACCTCAAAAGGTCGAACTCTTTAAAGGAACCATTCGTTCCAACTTGACTCTAGGTTT CAATCAAGAAGTATCTGACCAGGAACTCTGGCAGGCCTTGGAGATTGCGCAAGCTAAGGATTTTGTCAGTGAAAA GGAAGGACTCTTGGATGCTCTAGTTGAGGCAGGGGGGCGAAATTTCTCAGGTGGACAAAAACAAAGATTGTCTAT CGCCCGAGCAGTCTTGCGCCAGGCTCCGTTTCTCATCCTAGATGATGCAACCTCGGCACTGGATACCATTACAGAG

TCCAAGCTCTTGAAAGCTATTAGAGAAAATTTTCCAAACACGAGCTTAATTTTGATCTCTCAACGAACCTCAACTT TACAGATGGCGGACCAGATTCTCCTCTTGGAAAAAGGTGAGTTGCTAGCTGTTGGCAAGCACGATGACTTGATGA AATCCAGCCAAGTCTATTGTGAAATCAATGCATCCCAACATGGAAAGGAGGACTAG MKHLLSYFKPYIKESILAPLFKLLEAVFELLVPMVIAGIVDQSLPQGDQGHLWMQIGLLLIFAVIGVLVALIAQFYSAKA

AVGSAKELTNDLYRHILSLPKDSRDRLTTSSLVTRLTSDTYQIQTGINQFLRLFLRAPIIVFGAIFMAYRISAELTFWFLVL VAILTIVrVGLSRLVNPFYSSLRKKTDQLVQETRQQ QGMRVIRAFGQEKRELQIFQTLNQVYARLQEKTGFWSSLLTPL TYLIVNGTLLVIIWQGYISIQGGVLSQGALIALINYLLQILVELVK AMLINSLNQSYISVKRIEEVFVEAPEDIHSELEQKQ ATRDKVLQVQELTFTYPDAAQPSLRYISFDMTQGQILGIIGGTGSGKSSLVQLLLGLYPVDKGNIDLYQNGRSPLNLEQ WRSWIAYVPQKVELFKGTIRSNLTLGFNQEVSDQELWQALEIAQAKDFVSEKEGLLDALVEAGGRNFSGGQKQRLSIA

RAVLRQAPFLILDDATSALDTITESKLLKAIRENFPNTSLILISQRTSTLQMADQILLLEKGELLAVGKHDDLMKSSQVYC EINASQHGKEDZ

ID18 1224 bp

ATGAAACGTTCTCTCGACTCAAGAGTCGATTACAGTTTGCTCTTGCCAGTATTTTTTCTACTGGTCATCGGTGTGGT GGCTATCTATATAGCCGTTAGTCATGATTATCCCAATAATATTCTGCCCATTTTAGGGCAGCAGGTCGCCTGGATT GCCTTGGGGCTTGTGATTGGTTTTGTGGTCATGCTCTTTAATACAGAATTTCTTTGGAAGGTGACCCCCTTTCTATA TATTTTAGGCTTGGGACTTATGATCTTGCCGATTGTATTTTATAATCCAAGCTTAGTTGCATCAACGGGTGCCAAA AACTGGGTATCAATAAATGGAATTACCCTATTCCAACCGTCAGAATTTATGAAGATATCCTATATCCTCATGTTGG

CTCGTGTCATTGTCCAARRTACAAAGAAACATAAGGAATGGAGACGCACGGTTCCGCTGGACTTTTTGTTAATTTT CTGGATGATTCTCTTTACCATTCCAGTCCTAGTTCTTTTAGCACTTCAAAGTGACTTGGGGACGGCTTTGGTTTTTG TAGCCATTTTCTCAGGAATCGTTTTATTATCAGGGGTTTCTTGGAAAATTATTATCCCAGTATTTGTGACTGCTGTA ACAGGAGTTGCTGGTTTCTTAGCTATCTTTATTAGCAAGGACGGACGAGCTTTTCTTCACCAGATTGGAATGCCGA CCTACCAAATTAATCGGATTTTGGCTTGGCTCAATCCCTTTGAGTTTGCCCAAACAACGACTTACCAGCAGGCTCA

AGGGCAGATTGCCATTGGGAGTGGTGGCTTATTTGGTCAGGGATTTAATGCTTCGAATCTGCTTATCCCAGTTCGA GAGTCAGATATGATTTTTACGGTTATTGCAGAAGATTTTGGCTTTATTGGCTCTGTCCTGGTTATTGCCCTCTATCT CATGTTGATTTACCGTATGTTGAAGATTACTCTTAAATCAAATAACCAGTTCTACACTTATATTTCCACAGGTTTGA TTATGATGTTGCTCTTCCACATCTTTGAGAATATCGGTGCTGTGACTGGACTACTTCCTΓTGACGGGGATTCCCTTG CCTTTCATTΓCGCAAGGGGGATCAGCTATTATCAGTAATCTGATTGGTGTTGGTTTGCTTTTATCGATGAGTTACCA

SUBSTΓΓUTE SHEET (RULE 26) GACTAATCTAGCTGAAGAAAAGAGCGGAAAAGTCCCATTCAAACGGAAAAAGGTTGTATTAAAACAAATTAAATA A

MKRSLDSRVDYS LLPVFFLLVIGVVAIYIAVSHDYPNNILPILGQQVAWIALGLVIGFVVMLFNTEFLWKVTPFLYILGL GLMILPIVFYNPSLVASTGAKNWVSINGITLFQPSEFMKISYILMLARVIVQFTKKHKEWRRTVPLDFLLIFWMILFTIPVL

V LALQSDLGTALVFVAIFSGIVLLSGVSWKIIIPVFVTAVTGVAGFLAIFISKDGRAFLHQIGMPTYQINRILAWLNPFEF AQTTTYQQAQGQIAIGSGGLFGQGFNASNLLIPVRESDMIFTVIAEDFGFIGSVLVIALYLMLIYRMLKITLKSNNQFYTY ISTGLIMMLLFHIFENIGAVTGLLPLTGIP PFISQGGSAIISNLIGVGLL SMSYQTNLAEEKSGKVPF RKKVVLKQIKZ ID22 987 bp

ATGGTGGCTAAGAAAAAAATCTTATTTTTTATGTGGTCTTTTTCTCTTGGAGGTGGTGCAGAGAAGATTCTATCAA

CCATTGTTTCAAATCTGGATCCAGAAAAGTATGATATTGATATTCTTGAAATGGAGCACTTTGACAAGGGATATGA

ATCTGTTCCAAAGCATGTACGCATTTTAAAATCCCTTCAAGATTATCGCCAAACCAGATGGTTACGAGCTTTTTTG TGGAGAATGAGAATTTATTTTCCAAGACTGACTCGTCGTTTGCTTGTAAAAGATGATTATGATGTTGAAGTTTCTT

TTACCATTATGAATCCACCACTGTTGTTCTCTAAAAGAAGAGAAGTCAAGAAGATATCTTGGATTCATGGAAGTAT TGAAGAACTTCTTAAGGATAGCTCTAAAAGAGAATCACATAGAAGCCAGTTGGATGCTGCGAATACAATTGTAGG GATTTCAAAAAAGACCAGCAATTCTATCAAGGAAGTTTATCCAGATTATACTTCTAAATTACAGACAATCTACAAT GGATATGATTTTCAGACTATTCTAGAAAAATCTCAAGAGAAGATCGATATCGAGATTGCTCCTCAAAGTATCTGTA CTATCGGACGGATTGAGGAAAATAAGGGTTCTGACCGTGTAGTGGAAGTGATACGATTATTACACCAAGAGGGAA

AAAACTATCATCTCTATTTTATCGGGGCTGGTGATATGGAAGAGGAACTGAAAAAACGAGTCAAAGAGTATGGGA TTGAGGACTATGTACATTTCCTTGGTTATCAAAAAAATCCTTATCAGTATCTATCTCAGACGAAAGTTCTTTTGTCT ATGTCTAAACAAGAAGGTTTTCCTGGAGTGTATGTGGAGGCCTTGAGTCTGGGACTCCCTTTTATCTCTACGGACG TTGGAGGGGCTGAGGAATTATCCCAAGAAGGACGATTTGGACAAATCATTGAGAGCAATCAAGAGGCAGCTCAG GCGATTACTAATTACATGACTTCTGCCTCAAACTTrGATGTCGATGAGGCTAGCCAATTCATTCAACAATTTACAA

TTACAAAACAAATCGAACAAGTAGAAAAACTATTAGAGGAGTAG

MVA KKILFFMWSFSLGGGAEKILSTIVSNLDPEKYDIDILEMEHFDKGYESVPKHVRIL SLQDYRQTRWLRAFLWRM RIYFPRLTRRLLV DDYDVEVSFTIMNPPLLFSKRREVKKIS IHGSIEELLKDSSKRESHRSQLDAANTIVGISKKTSNSI EVYPDYTSKLQTIYNGYDFQTILEKSQE IDIEIAPQSICTIGRIEENKGSDRVVEVIRLLHQEGKNYHLYFIGAGDMEEEL

KKRVKEYGIEDYVHFLGYQKNPYQYLSQTKVLLSMSKQEGFPGVYVEALSLGLPFISTDVGGAEELSQEGRFGQIIESNQ EAAQAITNYMTSASNFDVDEASQFIQQFTITKQIEQVEKLLEEZ

ID23 1434 bp

ATGGAAACTGCATTAATTAGTGTGATTGTGCCAGTCTATAATGTGGCGCAGTACCTAGAAAAATCGATAGCTTCCA TrCAGAAGCAGACCTATCAAAATCTGGAAATTATTCTTGTTGATGATGGTGCAACAGATGAAAGTGGTCGCTTGTG TGATTCAATCGCTGAACAAGATGACAGGGTGTCAGTGCTTCATAAAAAGAACGAAGGATTGTCGCAAGCACGAAA TGATGGGATGAAGCAGGCTCACGGGGATTATCTGATTTTTATTGACTCAGATGATTATATCCATCCAGAAATGATT CAGAGCTTATATGAGCAATTAGTTCAAGAAGATGCGGATGTTTCGAGCTGTGGTGTCATGAATGTCTATGCTAATG

ATGAAAGCCCACAGTCAGCCAATCAGGATGACTATTTTGTCTGTGATTCTCAAACATTTCTAAAGGAATACCTCAT AGGTGAAAAAATACCTGGGACGATTTGCAATAAGCTAATCAAGAGACAGATTGCAACTGCCCTATCCTTTCCTAA GGGGTTGATTTACGAAGATGCCTATTACCATTTTGATTTAATCAAGTTGGCCAAGAAGTATGTGGTTAATACTAAA CCCTATTATTACTATTTCCATAGAGGGGATAGTATTACGACCAAACCCTATGCAGAGAAGGATTTAGCCTATATTG ATATCTACCAAAAGTTTTATAATGAAGTTGTGAAAAACTATCCTGACTTGAAAGAGGTCGCTTTTTTCAGATTGGC

CTATGCCCACTTCTTTATTCTGGATAAGATGTTGCTAGATGATCAGTATAAACAGTTTGAAGCCTATTCTCAGATT CATCGTTTTTTAAAAGGCCATGCCTTTGCTATTTCTAGGAATCCAATTTTCCGTAAGGGGAGAAGAATTAGTGCTT TGGCCCTATTCATAAATATTTCCTTATATCGATTCTTATTACTGAAAAATATTGAAAAATCTAAAAAATTACATTA G

METALISVIVPVYNVAQYLEKSIASIQ QTYQNLEIILVDDGATDESGRLCDSIAEQDDRVSVLHKKNEGLSQARNDGM KQAHGDYLIFIDSDDYIHPEMIQSLYEQLVQEDADVSSCGVMNVYANDESPQSANQDDYFVCDSQTFLKEYLIGEKIPG TICNKLIKRQIATALSFPKGLIYEDAYYHFDLIKLAKKYVVNTKPYYYYFHRGDSITTKPYAEKDLAYIDIYQKFYNEVV KNYPDLKEVAFFRLAYAHFFILDKMLLDDQYKQFEAYSQIHRFLKGHAFAISRNPIFRKGRRISALALFINISLYRFLLLK NIEKS KLHZ

ID24 735bp ATGAGAATCAAAGAGAAAACCAATAATATTAATGGAGGAATAAAAAATGTAAGTAAGCATTATGGTCATTCAATC

ATTCTCAAAGATATAAATTTTGCACTTAACAAGGGTGAAATTGTTGGTCTAGCAGGGAGAAATGGAGTTGGTAAG AGTACGTTGATGAAAATTCTTGTTCAGAATAATCAACCGACTTCAGGTAATATTATAAGCAGTGATAATGTTGGGT ATTTAATCGAAGAACCAAAATTATTTTTATCTAAAACAGGTTTAGAGAATTTAAAATATTTGTCAAATTTATATGG TGTTGACTACAATCAAGAAAGATTTAGATGTTTGATCCAAGAGTTAGATTTGACTCAGTCTATTAATAAAAAAGTA AAGACCTATTCTTTGGGTACAAAACAAAAATTAGCTTTGCTTCTAACTCTCGTTACGGAACCTGATATATTGATTT

SUBSTΓΓUTE SHEET (RULE 26) TAGATGAACCGACTAATGGTTTAGATATTGAATCATCACAAATAGTTTTAGCGGTTCTAAAAAAATTAGCTTTACA TGAAAATGTGGGAATTTTAATATCGAGTCATAAATTAGAAGACATTGAAGAAATTTGTGAGAGAGTTCTTTTCTTG GAGAACGGGCTTTTGACATTTCAAAAAGTAGGAAAAGATAGTCATAATTTCTTGTTTGAGATAGCTTTTTCATCAG CTACAGATAGAGACATTTTCATTACCAAACAAGAATTTTGGGATATTGTTTAG

MRIKEKTNNINGGIKNVSKHYGHSIILKDINFALN GEIVGLAGRNGVGKSTLMKILVQNNQPTSGNIISSDNVGYLIEEP

KLFLSKTGLENLKYLSNLYGVDYNQERFRCLIQELDLTQSINKKVKTYSLGTKQKLALLLTLVTEPDILILDEPTNGLDIE

SSQIVLAVLKKLALHENVGILISSHKLEDIEEICERVLFLENGLLTFQKVGKDSHNFLFEIAFSSATDRDIFITKQEFWDIVZ ID25 1704bp

ATGACTGAATTAGATAAACGTCACCGCAGTAGCATTTATGACAGCATGGTTAAATCACCTAACCGTGCTATGCTTC GTGCGACTGGTATGACAGATAAGGACTTTGAAACATCGATTGTGGGAGTGATTTCGACTTGGGCGGAAAATACAC CATGTAACATTCACTTGCATGATTTCGGGAAACTGGCTAAAGAAGGTGTCAAATCTGCAGGCGCTTGGCCTGTAC AGTTTGGAACCATTACCGTAGCGGACGGGATCGCTATGGGAACGCCTGGTATGCGTTTCTCTCTAACATCTCGTGA

CATCATCGCGGACTCCATCGAGGCGGCTATGAGTGGTCACAACGTGGATGCCTTCGTCGCTATCGGTGGCTGTGA CAAGAACATGCCTGGATCTATGATTGCTATTGCTAATATGGATATCCCAGCTATTTTCGCCTATGGTGGAACTATT GCACCGGGAAATCTTGATGGTAAAGATATCGACTTGGTTTCTGTCTTTGAAGGTATCGGAAAATGGAACCACGGT GACATGACAGCTGAGGACGTGAAACGTCTTGAATGTAATGCCTGCCCTGGCCCTGGTGGTTGTGGTGGTATGTAT ACTGCTAATACCATGGCAACTGCTATCGAAGTTCTAGGGATGAGTTTGCCAGGGTCATCCTCTCACCCAGCTGAAT

CAGCTGATAAGAAAGAAGATATCGAAGCAGCAGGACGTGCTGTTGTTAAGATGTTGGAACTTGGTCTCAAACCAT CAGATATCTTGACTCGTGAAGCCTTTGAAGATGCTATCACTGTAACGATGGCTCTCGGTGGTTCTACAAACGCCAC TCTTCACTTGCTCGCCATTGCCCATGCCGCAAATGTTGACTTGTCACTTGAGGACTTCAATACGATTCAAGAACGT GTGCCTCACTTGGCCGACTTGAAACCATCTGGTCAGTATGTCTTCCAAGACCTCTACGAAGTCGGTGGTGTCCCTG CGGTTATGAAGTATTTGTTGGCAAATGGTTTCCTTCACGGAGATCGCATCACATGTACTGGTAAGACTGTAGCTGA

AAACrrGGCTGACTTTGCAGACTTGACTCCAGGCCAAAAAGTTATCATGCCACTTGAAAATCCAAAACGTGCGGA TGGTCCGCTTATCATCTTGAACGGGAACCTTGCTCCTGACGGTGCAGTTGCCAAGGTATCAGGTGTTAAAGTGCGT CGTCACGTTGGGCCAGCTAAGGTCTTTGACTCAGAAGAAGATGCGATTCAGGCCGTTCTGACAGATGAAATCGTT GATGGCGATGTAGTCGTTGTTCGTTTTGTTGGACCTAAAGGTGGTCCTGGTATGCCTGAGATGCTATCACTTTCTTC AATGATTGTTGGTAAAGGTCAGGGAGATAAGGTGGCCCTCTTGACGGACGGACGTTTCTCTGGTGGTACTTATGGT

CTGGTTGTTGGACATATCGCTCCTGAAGCTCAGGATGGTGGACCAATTGCCTATCTCCGTACCGGCGATATCGTTA CGGTTGACCAAGATACCAAAGAAATTTCTATGGCCGTATCCGAAGAAGAACTTGAAAAACGCAAGGCAGAAACA ACCTTGCCACCACTTTACAGCCGTGGTGTCCTCGGTAAATATGCCCACATCGTATCATCTGCTTCACGCGGAGCCG TGACAGACTTCTGGAATATGGACAAGTCAGGTAAAAAATAA

MTELDKRHRSSIYDSMVKSPNRAMLRATGMTDKDFETSIVGVISTWAENTPCNIHLHDFGKLAKEGVKSAGAWPVQFG TITVADGIAMGTPGMRFSLTSRDIIADSIEAAMSGHNVDAFVAIGGCDKNMPGSMIAIANMDIPAIFAYGGTIAPGNLDG KDIDLVSVFEGIGKWNHGDMTAEDVKRLECNACPGPGGCGGMYTANTMATAIEVLGMSLPGSSSHPAESADKKEDIE AAGRAVVKMLELGLKPSDILTREAFEDAITVTMALGGSTNATLHLLAIAHAANVDLSLEDFNTIQERVPHLADLKPSGQ YVFQDLYEVGGVPAVMKYLLANGFLHGDRITCTGKTVAENLADFAD TPGQKVIMPLENPKRADGPLIILNGNLAPDG

AVAKVSGVKVRRHVGPAKVFDSEEDAIQAVLTDEIVDGDVVVVRFVGPKGGPGMPEMLSLSSMIVGKGQGDKVALLT DGRFSGGTYGLVVGHIAPEAQDGGPIAYLRTGDIVTVDQDTKEISMAVSEEELEKRKAETTLPPLYSRGVLGKYAHIVSS ASRGAVTDFWNMDKSG KZ ID26 274bp

ATGTTATAATAAAAATAAAGAATTTAAGGAGAAATACAATATGTCAATTTTTATTGGAGGAGCATGGCCATATGC AAACGGTTCGTTACATATTGGTCACGCGGCAGCGCTTTTACCGGGGGATATTCTTGCAAGATACTATCGTCAGAA GGGAGAGGAAGTTTTATATGTTTCTGGAAGTGATTGTAATGGAACCCCTATTTCTATCAGAGCTAAAAAAGAAAA TAAGTCTGTGAAAGAAATTGCTGATTTTTATCATAAGGAATTTAATCCA

CYNKNKEFKEKYNMSIFIGGAWPYANGSLHIGHAAALLPGDILARYYRQKGEEVLYVSGSDCNGTPISIRAKKENKSVK EIADFYHKEFNP ID28 1065bp

ATGACAACATTATTTTCAAAAATTAAAGAAGTAACAGAACTTGCTGCAGTCTCAGGTCATGAAGCGCCTGTCCGT

GCTTATCTTCGTGAAAAGTTGACACCGCATGTGGATGAAGTGGTGACAGATGGCTTGGGTGGTATTTTTGGTATCA

AACATTCAGAAGCTGTGGATGCACCGCGCGTCTTGGTCGCTTCTCATATGGACGAAGTTGGTTTTATGGTCAGCGA AATCAAGCCAGATGGTACCTTCCGTGTCGTAGAAATCGGTGGCTGGAACCCCATGGTGGTTAGCAGCCAACGTTT

CAAACTCTTGACTCGTGATGGTCATGAAATTCCTGTGATTTCAGGTTCTGTTCCTCCGCATTTGACTCGTGGAAAG GGGGGACCAACCATGCCAGCCATTGCCGATATCGTTTTTGATGGTGGTTTTGCGGACAAGGCTGAGGCAGAAAGT TTTGGCATCCGTCCTGGTGATACCATTGTACCAGATAGTTCTGCAATTTTGACAGCCAATGAAAAAAATATCATCT CAAAAGCTTGGGATAACCGCTACGGTGTCCTCATGGTAAGCGAGCTAGCTGAAGCTTTATCGGGTCAAAAACTCG GCAATGAACTCTATCTGGGTTCTAACGTCCAAGAAGAAGTTGGTCTGCGTGGCGCTCATACCTCTACAACCAAGTT

SUBSTΓΓUTE SHEET (RULE 26) TGACCCAGAAGTCTTCCTCGCAGTTGATTGCTCACCAGCAGGTGATGTCTACGGTGGTCAAGGCAAGATTGGAGA TGGAACCTTGATTCGTTTCTATGATCCAGGTCACTTGCTTCTCCCAGGGATGAAGGATTTCCTTTTGACAACGGCT GAAGAAGCTGGTATCAAGTACCAATACTACTGTGGTAAAGGCGGAACAGATGCAGGTGCAGCTCATCTGAAAAAT GGTGGTGTCCCATCAACAACTATCGGTGTCTGCGCTCGTTATATCCATTCTCACCAAACCCTCTATGCAATGGATG ACTTCCTAGAAGCGCAAGCTTTCTTACAAGCCTTGGTGAAGAAATTGGATCGTTCAACGGTTGATTTGATTAAACA

TTATTAA

MTTLFSKIKEVTELAAVSGHEAPVRAYLREKLTPHVDEVVTDGLGGIFGIKHSEAVDAPRVLVASHMDEVGFMVSEIKP DGTFRVVEIGGWNPMVVSSQRFK LTRDGHEIPVISGSVPPHLTRGKGGPTMPAIADIVFDGGFADKAEAESFGIRPGDT IVPDSSAILTANEKNΠSKAWDNRYGVLMVSELAEALSGQKLGNELYLGSNVQEEVGLRGAHTSTTKFDPEVFLAVDCS

PAGDVYGGQGKIGDGTLIRFYDPGHLLLPGMKDFLLTTAEEAGIKYQYYCGKGGTDAGAAHLKNGGVPSTTIGVCARY IHSHQTLYAMDDFLEAQAFLQALVKKLDRSTVDLIKHYZ

ID31 1182bp

ATGGAATTTTCTATGAAATCAGTCAAAGGACTACTCTTTATCATAGCTAGTTTTATCTTGACTCTTTTGACTTGGAT GAACACTTCTCCCCAATTCATGATTCCAGGACTAGCTTTAACAAGCCTATCTCTGACTTTTATCCTAGCCACTCGT CTCCCACTACTAGAAAGCTGGTTTCACAGTTTGGAGAAGGTCTACACCGTCCACAAATTCACAGCCTTTCTCTCAA TCATCCTACTAATCTTTCATAACTTTAGTATGGGCGGTTTGTGGGGCTCTCGCTTAGCTGCTCAGTTTGGCAATCTT GCCATCTATATCTTTGCCAGCATCATCCTTGTCGCCTATTTAGGCAAATACATCCAATACGAAGCTTGGCGATGGA

TTCACCGCCTGGTTTACCTAGCCTATATTTTAGGACTCTTTCACATCTACATGATAATGGGCAATCGTCTCCTTACA TTTAATCTTCTAAGTTTTCTTGTTGGTAGCTATGCCCTTTTAGGCTTACTAG^

CAAAAGATTTCCTTCCCCTATCTAGGGAAAATTACCCATCTCAAACGCTTAAATCACGATACTAGAGAAATTCAA ATCCATCTTAGCAGACCTTTCAACTATCAATCAGGACAATTTGCCTTTCTAAAGATTTTCCAAGAAGGCTTTGAAA GTGCTCCGCATCCCT I CTATCTCAGGAGGTCATGGTCAAACTCTTTACTTTACTGTTAAAACTTCAGGCGACCA

TACCAAGAATATCTATGATAATCTTCAAGCCGGCAGCAAAGTAACCCTAGACAGAGCTTACGGACACATGATCAT AGAAGAAGGACGAGAAAATCAGGTTTGGATTGCTGGAGGTATTGGGATCACCCCCTTCATCTCTTACATCCGTGA ACATCCTATTTTAGATAAACAGGTTCACTTCTACTATAGCTTCCGTGGAGATGAAAATGCAGTCTACCTAGATTTA CTCCGTAACTATGCTCAGAAAAATCCTAATTTTGAACTCCATCTAATCGACAGTACGAAAGACGGCTATCTTAATT TTGAACAAAAAGAAGTGCCCGAACATGCAACCGTCTATATGTGTGGTCCTATTTCTATGATGAAGGCACTTGCCA

AACAGATTAAGAAACAAAATCCAAAAACAGAGCATATTTAC

MEFSMKSVKGLLFIIASFILTLLTWMNTSPQFMIPGLALTSLSLTFI ATRLPLLESWFHSLEKVYTVHKFTAFLSIILLIFH NFSMGGLWGSRLAAQFGN AIYIFASIILVAYLGKYIQYEAWRWIHRLVYLAYILGLFHIYMIMGNRL TFNLLSFLVGS YALLGLLAGFYIIFLYQKISFPYLGKITHLKRLNHDTREIQIHLSRPFNYQSGQFAFLKIFQEGFESAPHPFSISGGHGQTLY

FTV TSGDHTKNIYDNLQAGSKVTLDRAYGHMIIEEGRENQVWIAGGIGITPFISYIREHPILDKQVHFYYSFRGDENAV YLDLLRNYAQKNPNFELHLIDSTKDGYLNFEQKEVPEHATVYMCGPISMMKALAKQIKKQNPKTEHIY

ID32 900bp

ATGACTTrrAAATCAGGCTTTGTAGCCATTTTAGGACGTCCCAATGTTGGGAAGTCAACCTTTTTAAATCACGTTA TGGGGCAAAAGATTGCCATCATGAGTGACAAGGCGCAGACAACGCGCAATAAAATCATGGGAATTTACACGACTG ATAAGGAGCAAATTGTCTTTATCGACACACCAGGGATTCACAAGCCTAAAACAGCTCTCGGAGATTTCATGGTTG AGTCTGCCTACAGTACCCTTCGCGAAGTGGACACTGTTCTTTTCATGGTGCCTGCTGATGAAGCGCGTGGTAAGGG GGACGATATGATTATCGAGCGTCTCAAGGCTGCCAAGGTTCCTGTGATTTTGGTGGTGAATAAAATCGATAAGGTC

CATCCAGACCAGCTCTTGTCTCAGATTGATGACTTCCGTAATCAAATGGACTTTAAGGAAATTGTTCCAATCTCAG CCCTTCAGGGAAATAACGTGTCTCGTCTAGTGGATATTTTGAGTGAAAATCTGGATGAAGGTTTCCAATATTTCCC GTCTGATCAAATCACAGACCATCCAGAACGTTTCTTGGTTTCAGAAATGGTTCGCGAGAAAGTCTTGCACCTAACT CGTGAAGAGATTCCGCATTCTGTAGCAGTAGTTGTTGACTCTATGAAACGAGACGAAGAGACAGACAAGGTTCAC ATCCGTGCAACCATCATGGTCGAGCGCGATAGCCAAAAAGGGATTATCATCGGTAAAGGTGGCGCTATGCTTAAG

AAAATCGGTAGCATGGCCCGTCGTGATATCGAACTCATGCTAGGAGACAAGGTCTTCCTAGAAACCTGGGTCAAG GTCAAGAAAAACTGGCGCGATAAAAAGCTAGATTTGGCTGACTTTGGCTATAATGAAAGAGAATACTAA

MTFKSGFVAILGRPNVGKSTFLNHVMGQKIAIMSDKAQTTRNKIMGIYTTDKEQIVFIDTPGIHKPKTALGDFMVESAYS TLREVDTVLFMVPADEARGKGDDMIIERLKAAKVPVILVVNKIDKVHPDQLLSQIDDFRNQMDFKEIVPISALQGNNVS

RLVDILSENLDEGFQYFPSDQITDHPERFLVSEMVREKVLHLTREEIPHSVAVVVDSMKRDEETDKVHIRATIMVERDSQ KGIIIGKGGAMLKKIGSMARRDIELMLGDKVFLETWVKVKKNWRDKKLDLADFGYNEREYZ

ID33 855bp

CTGCTTCTTGTTTTTACAGAAGGAGGACTTATGCCTGAATTACCTGAGGTTGAAACCGTTTGTCGTGGCTTAGAAA AATTGATTATAGGAAAGAAGATTTCGAGTATAGAAATTCGCTACCCCAAGATGATTAAGACGGATTTGGAAGAGT TTCAAAGGGAATTGCCTAGTCAGATTATCGAGTCAATGGGACGTCGTGGAAAATATTTGCTTTTTTATCTGACAGA CAAGGTCTTGATTTCCCATTTGCGGATGGAGGGCAAGTATTTTTACTATCCAGACCAAGGACCTGAACGCAAGCAT GCCCATGTTTTCTTTCATTTTGAAGATGGTGGCACGCTTGTTTATGAGGATGTTCGCAAGTTTGGAACCATGGAAC

SUBSTΓΓUTE SHEET (RULE 26) TCTTGGTGCCTGACCTTTTAGACGTCTACTTTATTTCTAAAAAATTAGGTCCTGAACCAAGCGAACAAGACTTTGA TTTACAGGTCTTTCAATCTGCCCTTGCCAAGTCCAAAAAGCCTATCAAATCCCATCTCCTAGACCAGACCTTGGTA GCTGGACTTGGCAATATCTATGTGGATGAGGTTCTCTGGCGAGCTCAGGTTCATCCAGCTAGACCTTCCCAGACTT TGACAGCAGAAGAAGCGACTGCCATTCATGACCAGACCATTGCTGTTTTGGGCCAGGCTGTTGAAAAAGGTGGCT CCACCATTCGGACTTATACCAATGCCTTTGGGGAAGATGGAAGCATGCAGGACTTTCATCAGGTCTATGATAAGA

CTGGTCAAGAATGTGTACGCTGTGGTACCATCATTGAGAAAATTCAACTAGGCGGACGTGGAACCCACTTTTGTCC AAACTGTCAAAGGAGGGACTGA

MLLVFTEGGLMPELPEVETVCRGLEKLIIGKKISSIEIRYPKMIKTDLEEFQRELPSQIIESMGRRGKYLLFYLTDKVLISHL RMEGKYFYYPDQGPERKHAHVFFHFEDGGTLVYEDVRKFGTMELLVPDLLDVYFISKKLGPEPSEQDFDLQVFQSALA

KSKKPIKSHLLDQTLVAGLGNIYVDEVLWRAQVHPARPSQTLTAEEATAIHDQTIAVLGQAVEKGGSTIRTYTNAFGED GSMQDFHQVYDKTGQECVRCGTIIEKIQLGGRGTHFCPNCQRRDZ

ID34 633bp

TTGTCCAAACTGTCAAAGGAGGGACTGATGGGAAAAATCATCGGAATCACTGGGGGAATTGCCTCTGGTAAGTCA ACTGTGACAAATTTTCTAAGACAGCAAGGCTTTCAAGTAGTGGATGCCGACGCAGTCGTCCACCAACTACAGAAA CCTGGTGGTCGTCTGTTTGAGGCTCTAGTACAGCACTTTGGGCAAGAAATCATTCTTGAAAACGGAGAACTCAATC GCCCTCTCCTAGCTAGTCTCATCTTTTCAAATCCTGATGAACGAGAATGGTCTAAGCAAATTCAAGGGGAGATTAT CCGTGAGGAACTGGCTACTTTGAGAGAACAGTTGGCTCAGACAGAAGAGATTTTCTTCATGGATATTCCCCTACTT

TTTGAGCAGGACTACAGCGATTGGTTTGCTGAGACTTGGTTGGTCTATGTGGACCGAGATGCCCAAGTGGAACGC TTAATGAAAAGGGACCAGTTGTCCAAAGATGAAGCTGAGTCTCGTCTGGCAGCCCAGTGGCCTTTAGAAAAAAAG AAAGATTTGGCCAGCCAGGTTCTTGATAATAATGGCAATCAGAACCAGCTTCTTAATCAAGTGCATATCCTTCTTG AGGGAGGTAGGCAAGATGACAGAGATTAA

MSKLSKEGLMGKIIGITGGIASGKSTVTNFLRQQGFQVVDADAVVHQLQKPGGRLFEALVQHFGQEIILENGELNRPLL

ASLIFSNPDEREWSKQIQGEIIREELATLREQLAQTEEIFFMDIPLLFEQDYSDWFAETWLVYVDRDAQVERLMKRDQLS

KDEAESRLAAQWPLEKKKDLASQVLDNNGNQNQLLNQVHILLEGGRQDDRDZ ID35 1269bp

TTGATAATAATGGCAATCAGAACCAGCTTCTTAATCAAGTGCATATCCTTCTTGAGGGAGGTAGGCAAGATGACA GAGATTAACTGGAAGGATAATCTGCGCATTGCCTGGTTTGGTAATTTTCTGACAGGAGCCAGTATTTCTTTGGTTG TACCTTTTATGCCCATCTTCGTGGAAAATCTAGGTGTAGGGAGTCAGCAAGTCGCTTTTTATGCAGGCTTAGCAAT TTCTGTCTCTGCTATITCCGCGGCGCTCTTTTCTCCTATTTGGGGTATTCTTGCTGACAAATACGGCCGAAAACCCA

TGATGATTCGGGCAGGTCTTGCTATGACTATCACTATGGGAGGCTTGGCCTTTGTCCCAAATATCTATTGGTTAAT CTTTCTTCGRRRACTAAACGGTGTATTTGCAGGTTTTGTTCCTAATGCAACGGCACTGATAGCCAGTCAGGTTCCA AAGGAGAAATCAGGCTCTGCCTTAGGTACTTTGTCTACAGGCGTAGTTGCAGGTACTCTAACTGGTCCCTTTATTG GTGGCTTTATCGCAGAATTATTTGGCATTCGTACAGTTTTCTTACTGGTTGGTAGTTTTCTATTTTTAGCTGCTATTT TGACTATTTGCTTTATCAAGGAAGATTTTCAACCAGTAGCCAAGGAAAAGGCTATΓCCAACAAAGGAATTATTTAC

CTCGGTTAAATATCCCTATCΓITTGCTCAATCTCTTTTTAACCAGTTTTGTCATCCAATTTTCAGCTCAATCGATTG GCCCTATTTTGGCTCTTTATGTACGCGACTTAGGGCAGACAGAGAATCTTCTTTTTGTCTCTGGTTTGATTGTGTCC AGTATGGGCTTTTCCAGCATGATGAGTGCAGGAGTCATGGGCAAGCTAGGTGACAAGGTGGGCAATCATCGTCTC TTGGTTGTCGCCCAGTTTTATTCAGTCATCATCTATCTCCTCTGTGCCAATGCCTCTAGCCCCCTTCAACTAGGACT CTATCGTTTCCTCTTTGGATTGGGAACCGGTGCCTTGATTCCCGGGGTTAATGCCCTACTCAGCAAAATGACTCCC

AAAGCCGGCATTTCGAGGGTCΓTTGCCTTCAATCAGGTATTCTTTTATCTGGGAGGTGTTGTTGGTCCCATGGCAG GTTCTGCAGTAGCAGGTCAATTTGGCTACCATGCTGTCTTTTATGCGACAAGCCTTTGTGTTGCCTTTAGTTGTCTC TTTAACCTGATTCAATTTCGAACATTATTAAAAGTAAAGGAAATCTAG MIIMAIRTSFLI CISFLREVGKMTEINWKDNLRIAWFGNFLTGASISLVVPFMPIFVENLGVGSQQVAFYAGLAISVSAIS

AALFSPIWGILADKYGRKPMMIRAGLAMTITMGGLAFVPNIYWLIFLRLLNGVFAGFVPNATALIASQVPKEKSGSALG TLSTGVVAGTLTGPFIGGFIAELFGIRTVFLLVGSFLFLAAILTICFIKEDFQPVA E AIPTKELFTSVKYPYLLLNLFLTS FVIQFSAQSIGPILALYVRDLGQTENLLFVSGLIVSSMGFSSMMSAGVMGKLGDKVGNHRLLVVAQFYSVIIYLLCANAS SPLQLGLYRFLFGLGTGALIPGVNALLSKMTPKAGISRVFAFNQVFFYLGGVVGPMAGSAVAGQFGYHAVFYATSLCV AFSC FNLIQFRTLLKV EIZ

ID36 1311bp

ATGGCCCTACCAACTATTGCCATTGTAGGACGTCCCAATGTTGGGAAATCAACCCTATTTAATCGGATCGCTGGTG AGCGAATCTCCATTGTAGAAGATGTCGAAGGAGTGACACGTGACCGTATTTATGCAACGGGTGAGTGGCTCAATC GTTCTTTTAGCATGATTGATACAGGAGGAATTGATGATGTCGATGCTCCTTTCATGGAACAAATCAAGCACCAGGC

AGAAATTGCCATGGAAGAAGCAGATGTTATCGTTTTTGTCGTGTCTGGTAAGGAAGGAATTACTGATGCAGACGA ATACGTAGCTCGTAAGCTTTATAAGACCCACAAACCAGTTATCCTCGCAGTCAACAAGGTGGACAACCCTGAGAT GAGAAATGATATATATGATTTCTATGCTCTCGGTTTGGGTGAACCATTGCCTATCTCATCTGTCCATGGAATCGGT ACAGGGGATGTGCTAGATGCGATCGTAGAAAATCTTCCAAATGAATATGAGGAAGAAAATCCAGATGTCATTAAG TTTAGCTTGATTGGTCGTCCTAACGTTGGAAAATCAAGCTTGATCAATGCTATCTTGGGAGAAGACCGTGTTATTG CTAGTCCTGTTGCTGGAACAACTCGTGATGCCATTGATACCCACTTTACAGATACAGATGGTCAAGAGTTTACCAT GATTGATACGGCTGGTATGCGTAAGTCTGGTAAGGTTTATGAAAATACTGAGAAATACTCTGTTATGCGTGCCATG CGTGCTATTGACCGTTCAGATGTGGTCTTGATGGTCATCAATGCGGAAGAAGGCATTCGTGAGTACGACAAGCGT ATCGCAGGATTTGCCCATGAAGCTGGTAAAGGGATGATTATCGTGGTCAACAAGTGGGATACGCTTGAAAAAGAT AACCACACTATGAAAAACTGGGAAGAAGATATCCGTGAGCAGTTCCAATACCTGCCTTACGCACCGATTATCTTT

GTATCAGCTTTAACCAAGCAACGTCTCCACAAACTTCCTGAGATGATTAAGCAAATCAGCGAAAGTCAAAATACA CGTATTCCATCAGCTGTCTTGAACGATGTCATCATGGATGCCATTGCCATCAACCCAACACCGACAGACAAAGGA AAACGTCTCAAGATTTTCTATGCGACCCAAGTGGCAACCAAACCACCAACCTTTGTCATCTTTGTCAATGAAGAAG AACTCATGCACTTTTCTTACCTGCGTTTCTTGGAAAATCAAATCCGCAAGGCCTTTGTTTTTGAGGGAACACCGAT TCATCTCATCGCAAGAAAACGCAAATAA

MALPTIAIVGRPNVGKSTLFNRIAGERISIVEDVEGVTRDRIYATGEWLNRSFSMIDTGGIDDVDAPFMEQIKHQAEIAM EEADVIVFVVSGKEGITDADEYVARKLYKTHKPVILAVNKVDNPEMRNDIYDFYALGLGEPLPISSVHGIGTGDVLDAI VENLPNEYEEENPDVIKFSLIGRPNVGKSSLINAILGEDRVIASPVAGTTRDAIDTHFTDTDGQEFTMIDTAGMRKSGKV YENTEKYSVMRAMRAIDRSDVVLMVINAEEGIREYDKRIAGFAHEAGKGMIIVVNKWDTLEKDNHTMKNWEEDIREQ

FQYLPYAPIIFVSALT QRLHKLPEMIKQISESQNTRIPSAVLNDVIMDAIAINPTPTDKGKRLKIFYATQVATKPPTFVIFV NEEELMHFSYLRFLENQIRKAFVFEGTPIHLIARKRKZ

ID37 714bp

ATGACAGAAACCATTAAATTGATGAAGGCTCATACTTCAGTGCGCAGGTTTAAAGAGCAAGAAATTCCCCAAGTA GACTTAAATGAGATTTTGACAGCAGCCCAGATGGCATCATCTTGGAAGAATTTCCAATCCTACTCTGTGATTGTGG TACGAAGTCAAGAGAAGAAAGATGCCTTGTATGAATTGGTACCTCAAGAAGCCATTCGCCAGTCTGCTGTTTTCCT TCTCTTTGTCGGAGATTTGAACCGAGCAGAAAAGGGAGCCCGACTTCATACCGACACCTTCCAACCCCAAGGTGT GGAAGGTCTCTTGATTAGTTCGGTCGATGCAGCTCTTGCTGGACAAAACGCCTTGTTGGCAGCTGAAAGCTTGGGC

TATGGTGGTGTGATTATCGGTTTGGTTCGATACAAGTCTGAAGAAGTGGCAGAGCTCTTTAACCTACCTGACTACA CCTATTCTGTCTTTGGGATGGCACTGGGTGTGCCAAATCAACATCATGATATGAAACCGAGACTGCCACTAGAGA ATGTTGTCTTTGAGGAAGAATACCAAGAACAGTCAACTGAGGCAATCCAAGCTTATGACCGTGTTCAGGCTGACT ATGCTGGGGCGCGTGCGACCACAAGCTGGAGTCAGCGCCTAGCAGAACAGTTTGGTCAAGCTGAACCAAGCTCAA CTAGAAAAAATCTTGAACAGAAGAAATTATTGTAG

MTETIKLMKAHTSVRRFKEQEIPQVDLNEILTAAQMASSWKNFQSYSVIVVRSQEK DALYELVPQEAIRQSAVFLLFV GDLNRAE GARLHTDTFQPQGVEGLLISSVDAALAGQNALLAAESLGYGGVIIGLVRYKSEEVAELFNLPDYTYSVFG MALGVPNQHHDMKPRLPLENVVFEEEYQEQSTEAIQAYDRVQADYAGARATTSWSQRLAEQFGQAEPSSTRKNLEQK KLLZ

IP38 729bp

ATGACAGAAATTAGACTAGAGCACGTCAGTTATGCCTATGGTCAGGAGAGGATTTTAGAGGATATCAACCTACAG GTGACTTCAGGCGAAGTGGTTTCCATCCTAGGCCCAAGTGGTGTTGGAAAGACCACCCTCTTTAATCTAATCGCTG

GGATTTTAGAAGTTCAGTCAGGGAGAATTGTCCTTGATGGTGAAGAAAATCCCAAGGGGCGCGTGAGTTATATGT TGCAAAAGGATCTGCTCTTGGAGCACAAGACGGTGCTTGGAAATATCATTCTGCCCCTCTTGATTCAAAAGGTGG ATAAGGCAGAAGCTATTTCCCGAGCGGATAAAATTCTTGCGACCTTCCAGCTGACAGCTGTAAGAGACAAGTATC CTCATGAACTTAGCGGTGGGATGCGCCAGCGTGTAGCCTTACTCCGGACCTACCTTTTTGGGCACAAGCTCTTTCT CTTAGATGAGGCCTTTAGCGCCTTGGATGAGATGACAAAGATGGAACTCCACGCTTGGTATCTTGAGATTCACAA

GCAGTTGCAGCTAACAACCCTGATCATCACGCATAGTATTGAGGAGGCCCTCAATCTCAGCGACCGTATCTATATC TTGAAAAATCGCCCTGGGCAGATTGTTTCAGAAATTAAACTAGATTGGTCTGAAGATGAGGACAAGGAAGTCCAA AAGATTGCCTACAAACGTCAAATTTTGGCGGAATTAGGCTTAGATAAGTAG MTEIRLEHVSYAYGQERILEDINLQVTSGEVVSILGPSGVG TTLFNLIAGILEVQSGRIVLDGEENP GRVSYMLQKDLL

LEHKTV GNIILPLLIQKVDKAEAISRADKILATFQLTAVRDKYPHELSGGMRQRVALLRTYLFGHKLFLLDEAFSALDE MTKMELHAWYLEIHKQLQ TTLIITHSIEEALNLSDRIYILKNRPGQIVSEIKLDWSEDEDKEVQKIAYKRQILAELGLDK Z 1D39 2433bp

ATGAACTATTCAAAAGCATTGAATGAATGTATCGAAAGTGCCTACATGGTTGCTGGACATTTTGGAGCTCGTTATC TAGAGTCGTGGCACTTGTTGATTGCCATGTCTAATCACAGTTATAGTGTAGCAGGGGCAACTTTAAATGATTATCC GTATGAGATGGACCGTTTAGAAGAGGTGGCTTTGGAACTGACTGAAACGGACTATAGCCAGGATGAAACCTTTAC GGAATTGCCGTTCTCCCGTCGTTTGCAGGTTCTTTTTGATGAAGCAGAGTATGTAGCGTCAGTGGTCCATGCTAAG

GTACTAGGGACAGAGCACGTCCTCTATGCGATTTTGCATGATAGCAATGCCTTGGCGACTCGTATCTTGGAGAGG GCTGGTTTTTCTTATGAAGACAAGAAAGATCAGGTCAAGATTGCTGCTCTTCGTCGAAATTTAGAAGAACGGGCA GGCTGGACTCGTGAAGATCTCAAGGCTTTACGCCAACGCCATCGTACAGTAGCTGACAAGCAAAATTCTATGGCC AATATGATGGGCATGCCGCAGACTCCTAGTGGTGGTCTCGAGGATTATACGCATGATTTGACAGAGCAAGCGCGT TCTGGCAAGTTAGAACCAGTCATCGGTCGGGACAAGGAAATCTCACGTATGATTCAAATCTTGAGCCGGAAGACT AAGAACAACCCTGTCTTGGTTGGGGATGCTGGTGTCGGGAAAACAGCTCTGGCGCTTGGTCTTGCCCAGCGTATTG CTAGTGGTGACGTGCCTGCGGAAATGGCTAAGATGCGCGTGTTAGAACTTGATTTGATGAATGTCGTTGCAGGGA CACGCTTCCGTGGTGACTTTGAAGAACGCATGAATAATATCATCAAGGATATTGAAGAAGATGGCCAAGTCATCC TCTTTATCGATGAACTCCACACCATCATGGGTTCTGGTAGCGGGATTGATTCGACTCTGGATGCGGCCAATATCTT GAAACCAGCCTTGGCGCGTGGAACTTTGAGAACGGTTGGTGCCACTACTCAGGAAGAATATCAAAAACATATCGA

AAAAGATGCGGCACTTTCTCGTCGTTTCGCTAAAGTGACGATTGAAGAACCAAGTGTGGCAGATAGTATGACTAT TTTACAAGGTTTGAAGGCGACTTATGAGAAACATCACCGTGTACAAATCACAGATGAAGCGGTTGAAACAGCGGT TAAGATGGCTCATCGTTATTTAACCAGTCGTCACTTGCCAGACTCTGCTATCGATCTCTTGGATGAGGCGGCAGCA ACAGTGCAAAATAAGGCAAAGCATGTAAAAGCAGACGATTCAGATTTGAGTCCAGCTGACAAGGCCCTGATGGAT GGCAAGTGGAAACAGGCAGCCCAGCTAATCGCAAAAGAAGAGGAAGTACCTGTCTACAAAGACTTGGTGACAGA GTCTGATATTTTGACCACCTTGAGTCGCTTGTCAGGAATCCCAGTTCAAAAACTGACTCAAACGGATGCTAAGAAG TATTTAAATCTTGAAGCAGAACTCCATAAACGGGTTATCGGTCAAGATCAAGCTGTTTCAAGCATTAGCCGTGCCA TTCGCCGCAACCAGTCAGGGATTCGCAGTCATAAGCGTCCGATTGGTTCCTTTATGTTCCTAGGGCCTACAGGTGT CGGGAAAACTGAATTAGCCAAGGCTCTGGCAGAAGTTCITTTTGACGACGAATCAGCCCTTATCCGCTTTGATATG AGTGAGTATATGGAGAAATTTGCAGCTAGTCGTCTCAACGGAGCTCCTCCAGGCTATGTAGGATATGAAGAAGGT

GGGGAGTTGACAGAGAAGGTTCGCAATAAACCCTATTCCGTTCTCCTCTTTGATGAGGTAGAGAAGGCCCACCCA GATATCΓI AATGTTCTCTTGCAGGTTCTGGATGACGGTGTCTTGACAGATAGCAAGGGACGCAAGGTCGATTTTT CAAATACCATTATCATTATGACATCGAATCTAGGTGCGACTGCCCTTCGTGATGATAAGACTGTTGGTTTTGGGGC TAAGGATATTCGTTTTGACCAGGAAAATATGGAAAAACGCATGTTTGAAGAACTGAAAAAAGCTTATAGACCGGA ATTCATCAACCGTATTGATGAGAAGGTGGTCTTCCATAGCCTATCTAGTGATCATATGCAGGAAGTGGTGAAGATT ATGGTCAAGCCTTRAGTGGCAAGTTTGACTGAAAAAGGCATTGACTTGAAATTACAAGCTTCAGCTCTGAAATTGT TAGCAAATCAAGGATATGACCCAGAGATGGGAGCTCGCCCACTTCGCAGAACCCTGCAAACAGAAGTGGAGGAC AAGTTGGCAGAACTTCTTCTCAAGGGAGATTTAGTGGCAGGCAGCACACTTAAGATTGGTGTCAAAGCAGGCCAG TTAAAATTTGATATTGCATAA

MNYSKALNECIESAYMVAGHFGARYLESWHLLIAMSNHSYSVAGATLNDYPYEMDRLEEVALELTETDYSQDETFTE LPFSRRLQVLFDEAEYVASVVHAKVLGTEHVLYAILHDSNALATRILERAGFSYEDKKDQVKIAALRRNLEERAGWTR EDLKALRQRHRTVADKQNSMANMMGMPQTPSGGLEDYTHDLTEQARSGKLEPVIGRDKEISRMIQILSRKTKNNPVLV GDAGVGKTALALGLAQRIASGDVPAEMAKMRVLELDLMNVVAGTRFRGDFEERMNNIIKDIEEDGQVILFIDELHTIM GSGSGIDSTLDAANILKPALARGTLRTVGATTQEEYQKHIEKDAALSRRFA VTIEEPSVADSMTILQGLKATYEKHHRV

QITDEAVETAVKMAHRYLTSRHLPDSAIDLLDEAAATVQNKAKHVKADDSDLSPADKALMDGKWKQAAQLIAKEEEV PVYKDLVTESDILTTLSRLSGIPVQKLTQTDAKKYLNLEAELHKRVIGQDQAVSSISRAIRRNQSGIRSHKRPIGSFMFLGP TGVGKTELAKALAEVLFDDESALIRFDMSEYMEKFAASRLNGAPPGYVGYEEGGELTEKVRNKPYSVLLFDEVEKAHP DIFNVLLQVLDDGVLTDSKGRKVDFSNTIIIMTSNLGATALRDDKTVGFGA DIRFDQENMEKRMFEELKKAYRPEFIN RIDEKVVFHSLSSDHMQEVVKIMVKPLVASLTEKGIDLKLQASALKLLANQGYDPEMGARPLRRTLQTEVEDKLAELL

LKGDLVAGSTLKIGVKAGQLKFDIAZ

ID40 1008bp ATGAAGAAAACATGGAAAGTGTTTTTAACGCTTGTAACAGCTCTTGTAGCTGTTGTGCTTGTGGCCTGTGGTCAAG

GAACTGCTTCTAAAGACAACAAAGAGGCAGAACTTAAGAAGGTTGACTTTATCCTAGACTGGACACCAAATACCA ACCACACAGGGCTTTATGTTGCCAAGGAAAAAGGTTATTTCAAAGAAGCTGGAGTGGATGTTGATTTGAAATTGC CACCAGAAGAAAGTTCTTCTGACTTGGTTATCAACGGAAAGGCACCATTTGCAGTGTATTTCCAAGACTACATGGC TAAGAAATTGGAAAAAGGAGCAGGAATCACTGCCGTTGCAGCTATTGTTGAACACAATACATCAGGAATCATCTC TCGTAAATCTGATAATGTAAGCAGTCCAAAAGACTTGGTTGGTAAGAAATATGGGACATGGAATGACCCAACTGA

ACTTGCTATGTTGAAAACCTTGGTAGAATCTCAAGGTGGAGACTTTGAGAAGGTTGAAAAAGTACCAAATAACGA CTCAAACTCAATCACACCGArrGCCAATGGCGTCTTTGATACTGCTTGGATTTACTACGGTTGGGATGGTATCCTT GCTAAATCTCAAGGTGTAGATGCTAACTTCATGTACTTGAAAGACTATGTCAAGGAGTTTGACTACTATTCACCAG TTATCATCGCAAACAACGACTATCTGAAAGATAACAAAGAAGAAGCTCGCAAAGTCATCCAAGCCATCAAAAAA GGCTACCAATATGCCATGGAACATCCAGAAGAAGCTGCAGATATTCTCATCAAGAATGCACCTGAACTCAAGGAA

AAACGTGACTTTGTCATCGAATCTCAAAAATACTTGTCAAAAGAATACGCAAGCGACAAGGAAAAATGGGGTCAA TTTGACGCAGCTCGCTGGAATGCTTTCTACAAATGGGATAAAGAAAATGGTATCCTTAAAGAAGACTTGACAGAC AAAGGCTTCACCAACGAATTTGTGAAATAA MKKTWKVFLTLVTALVAVVLVACGQGTASKDNKEAELKKVDFILDWTPNTNHTGLYVAKEKGYFKEAGVDVDLKLP

PEESSSDLVINGKAPFAVYFQDYMAKK EKGAGITAVAAIVEHNTSGIISRKSDNVSSPKDLVGKKYGTWNDPTELAML KTLVESQGGDFEKVEKVPNNDSNSITPIANGVFDTAWIYYGWDGILAKSQGVDANFMYLKDYVKEFDYYSPVIIANND YLKDNKEEARKVIQAIKKGYQYAMEHPEEAADILIKNAPELKEKRDFVIESQKYLSKEYASDKEKWGQFDAARWNAFY KWDKENGILKEDLTDKGFTNEFVKZ

ID41 762b

TTGATGAGAAACTTGAGAAGTATACTGAGACGACACATTAGTCTATTGGGCTTTCTCGGAGTATTGTCAATCTGGC

AGTTAGCAGGTTTTCT AAACTTCTCCCCAAGTTTATCCTGCCGACACCTCTTGAAATTCTCCAGCCCTTTGTTCGT GACAGAGAATTTCTCTGGCACCATAGCTGGGCGACCTTGAGAGTGGCTTTACTGGGGCTGATTTTGGGAGTTTTGA TTGCCTGTCTTATGGCTGTGCTCATGGATAGTTTGACTTGGCTCAATGACCTGATTTACCCTATGATGGTGGTCATT CAGACCATTCCGACCATTGCCATAGCTCCTATCCTGGTCTTGTGGCTAGGTTATGGGATTTTGCCCAAGATTGTCT TGATTATCTTAACGACAACCTTTCCCATCATCGTTAGTATTTTGGACGGTTTTAGGCATTGCGACAAGGATATGCT GACCTTGTTTAGTCTGATGCGGGCCAAGCCTTGGCAAATCCTGTGGCATTTTAAAATCCCAGTTAGCCTGCCTTAC TTTTATGCAGGTCTGAGGGTCAGTGTCTCCTACGCCTTTATCACAACTGTGGTATCTGAGTGGTTGGGAGGTTTTG

AAGGTCTTGGTGTTTATATGATTCAGTCTAAAAAACTGTTTCAGTATGATACCATGTTTGCCATTATTATTCTGGTG TCGATTATCAGTCTTTTGGGTATGAAGCTGGTCGATATCAGTGAAAAATATGTGATTAAATGGAAACGTTCGTAG

MMRNLRSILRRHISLLGFLGVLSIWQLAGFLKLLP FILPTPLEILQPFVRDREFLWHHSWATLRVALLGLILGVLIACLM AVLMDSLTWLNDLIYPMMVVIQTIPTIAIAPILVLWLGYGILPKIVLIILTTTFPIIVSILDGFRHCDKDMLTLFSLMRAKP

WQILWHFKIPVSLPYFYAGLRVSVSYAFITTVVSEWLGGFEGLGVYMIQSKKLFQYDTMFAIIILVSIISLLGMKLVDISE YVIKWKRSZ

ID42 372bp

TTGATΓTTTAATCCTATTΓGCTGTATGATAAGGGAAAAGAAAGGGGACAGAGATATGGCTTTTACCAATACCCACA TGCGATCTGCTAGTTTTGGTATTGTTACCAGCTTGCCTGATGACATCATTGACTCTTTTTGGTATATCATCGACCAT TTCTTAAAAAATGTCTTΓGAATTGGAAGAAGAACTCGAGTTTCAATTGCTTAATAACCAAGGAAAGATTACCTTCC ACTTTTCAAGTCAACACCTCCCTACAGCCATTGATTTTGACTTTAACCATCCTTTCGACCCTCGTTATCCCCCAAGA GTACTGGTTTTAGACATGGACGGTAGAGAAACTATCCTCCTCCCAGAAGAAAATGACCTATTTTAA

MIFNPICCMIRE KGDRDMAFTNTHMRSASFGIVTSLPDDIIDSFWYIIDHFLKNVFELEEELEFQLLNNQGKITFHFSSQ HLPTAIDFDFNHPFDPRYPPRVLVLDMDGRETILLPEENDLFZ ID43 1569bp

ACAGCGGTGTCATTCTATCTATTTTAAGAAAAGTAATAATCAATTGTTAAAAATAGTAAAAAAATTGGAGGTTCTG ATGAAATATTTTGTTCCTAATGAGGTATTCAGTATTCGTAAATTAAAGGTGGGGACTTGCTCGGTACTATTGGCAA TTTCAATTTTGGGAAGCCAAGGTATTTTATCGGATGAAGTTGTTACTAGTTCTTCACCGATGGCTACAAAAGAGTC TTCTAATGCAATTACTAATGATTTAGATAATTCACCAACTGTTAATCAGAATCGTTCTGCTGAAATGATTGCCTCT

AAΓΓCAACCACTAATGGTTTAGATAATTCGTTAAGTGTTAATAGCATCAGCTCTAATGGTACTATTCGTTCCAATT CACAATTAGACAACAGAACAGTTGAATCTACAGTAACATCTACTAATGAAAATAAGAGTTATAAGGAAGATGTTA TAAGTGACAGAATTATCAAAAAAGAATTTGAAGATACTGCTTTAAGTGTAAAAGATTATGGTGCAGTAGGTGATG GGATTCATGATGATCGACAAGCAATTCAAGATGCAATAGATGCTGCAGCTCAAGGGCTAGGTGGAGGAAATGTAT ATTTTCCTGAAGGAACTTATTTAGTAAAAGAAATTGTTTTTTTAAAAAGTCATACACACTTAGAATTGAATGAGAA

AGCTACAATTCTAAATGGTATAAATATTAAGAATCACCCTTCCATTGTTTTTATGACAGGTTTATTTACGGATGAT GGTGCGCAAGTAGAATGGGGCCCAACAGAAGATAT AGTTATTCTGGTGGTACGATTGATATGAACGGTGCTTTG AATGAAGAAGGAACTAAAGCAAAAAATCTACCACTTATAAATTCTTCAGGTGCATTTGCTATTGGGAATTCAAAT AACGTAACTATAAAAAATGTAACATTCAAGGATAGTTATCAAGGGCATGCTATTCAAATTGCAGGTTCGAAAAAT GTATTAGTTGATAATTCTCGTTTTCTTGGGCAAGCCTTACCCAAAACGATGAAGGATGGGCAAATCATAAGTAAGG

AGAGCATTCAGATTGAACCATTAACTAGAAAAGGTTTTCCTTATGCCTTGAATGATGATGGGAAAAAATCTGAAA ATGTGACTATTCAAAATTCCTATTTTGGCAAAAGTGATAAATCTGGGGAATTAGTAACAGCAATTGGCACACACTA TCAAACATTGTCGACACAGAACCCCTCTAATATTAAAATTCAAAATAATCATTTTGATAACATGATGTATGCAGGT GTACGTTTTACAGGATTCACTGATGTATTAATCAAAGGAAATCGCTTTGATAAGAAAGTTAAAGGAGAGAGTGTA CATTATCGAGAAAGCGGAGCAGCTTTAGTAAATGCTTATAGCTATAAAAACACTAAAGACCTATTAGATTTAAAT

AAACAGGTGGTTATCGCCGAAAATATATTTAATATTGCCGATCCTAAAACAAAAGCGATACGAGTTGCAAAAGAT AGTGCAGAATGTTTAGGAAAAGTATCAGATATTACTGTAACAAAAAATGTAATTAATAATAATTCTAAGGAAACA GAACAACCAAATATTGAATTATTACGAGTTAGTGATAATTTAGTAGTCTCAGAGAATAGT QRCHSIYFKKSNNQLLKIVKK EVLMKYFVPNEVFSIRKLKVGTCSVLLAISILGSQGILSDEVVTSSSPMATKESSNAITN

DLDNSPTVNQNRSAEMIASNSTTNGLDNSLSVNSISSNGTIRSNSQLDNRTVESTVTSTNENKSYKEDVISDRIIKKEFEDT ALSVKDYGAVGDGIHDDRQAIQDAIDAAAQGLGGGNVYFPEGTYLVKEIVFLKSHTHLELNEKATILNGINIKNHPSIVF MTGLFTDDGAQVEWGPTEDISYSGGTIDMNGA NEEGTKAKNLPLINSSGAFAIGNSNNVTIKNVTFKDSYQGHAIQIA GSKNVLVDNSRFLGQALPKTMKDGQIISKESIQIEPLTRKGFPYALNDDGKKSENVTIQNSYFGKSDKSGELVTAIGTHY QTLSTQNPSNIKIQNNHFDNMMYAGVRFTGFTDVLIKGNRFDKKVKGESVHYRESGAALVNAYSYKNTKDLLDLNKQ

VVIAENIFNIADPKTKAIRVAKDSAECLGKVSDITVTKNVINNNSKETEQPNIELLRVSDNLVVSENS

ID44 324bp GTGATGAAAGAAACTCAGCTATTAAAAGGTGTTCTTGAAGGTTGTGTCTTGGATATGATTGGTCAAAAAGAGCGG

TATGGTTATGAGTTGGTTCAGACTTTGCGAGAGGCTGGATTTGATACTATCGTTCCAGGAACTATTTATCCTTTGTT GCAAAAGTTAGAAAAAAATCAATGGATAAGAGGCGACATGCGCCCGTCGCCAGATGGTCCAGATCGGAAGTATTT TTCATTAATGAAAGAAGGAGAAGAGCGTGTCTCAGTCTTTTGGCAACAATGGGACGATTTGAGTCAAAAAGTAGA AGGGATTAAGAATGGGGGTTAA MMKETQLLKGVLEGCVLDMIGQKERYGYELVQTLREAGFDTIVPGTIYPLLQ LEKNQWIRGDMRPSPDGPDRKYFSL MKEGEERVSVFWQQWDDLSQKVEGIKNGGZ

IP45 816bp

ATGAAGAAAATGAAGTATTACGAAGAAACAAGCGCTTTGCTACATGAGTTTTCTGAGGAGAATCAAAAGTATTTT GAGGAGTTGTGGGAAAGTTTTAATCTTGCTGGATTTCTCTATGATGAAGACTATCTCAGAGAGCAGATCTATTTGA TGATGCTAGATTTCTCAGAAGCAGAACGAGATGGCATGAGTGCAGAGGATTATCTAGGTAAGAATCCTAAAAAAA TAATGAAAGAGATTCTCAAGGGAGCACCTCGCAGTTCTATCAAAGAGTCCCTTTTGACGCCAATTCTTGTCCTGGC GGTATTACGTTATTATCAACTACTAAGTGATTTTTCTAAAGGTCCTCTCTTAACAGTCAATTTGCTCACATTTTTAG GGCAACTTCTTATTTTTCTGATTGGATTTGGACTTGTGGCCACAATTTTACGAAGAAGTTTAGTCCAAGATTCTCCT AAAATGAAAATTGGCACT ACATTGTTGTTGGGACTATAGTTCTTCTAGTTGTTTTAGGATATGTAGGAATGGCAA GCTTCATACAAGAAGGAGCCTTTTATATTCCGGCTCCCTGGGATAGTΓΓGTCTGTCTTTACGATTTCGCTAGTTATC GGTATTTGGAATTGGAAAGAAGCGGTCTTTCGTCCATTTGTCAGTATGATTATTGCCCATCTTGTGGTGGGTTCTCT GCTCCGTTATTATGAGTGGATGGGAATTTCAAATGTTTTCCTTACAAAAGTTATΓCCTTTAGCTGTCCTCTTTATTG

GAATCITTGTCTTGTTCCGTGGGTTTAAGAAGATAAAATGGAGTGAAGTATAG

MKKMKYYEETSALLHEFSEENQKYFEELWESFNLAGFLYDEDYLREQIYLMMLDFSEAERDGMSAEDYLGKNPKKIM KEILKGAPRSSI ESLLTPILVLAVLRYYQLLSDFSKGPLLTVNLLTFLGQLLIFLIGFGLVATILRRSLVQDSPKMKIGTYI VVGTIVLLVVLGYVGMASFIQEGAFYIPAPWDSLSVFTISLVIGIWNWKEAVFRPFVS IIAHLVVGSLLRYYEWMGISN

VFLTKVIPLAVLFIGIFVLFRGFKKIKWSEVZ

ID46348bp CTGTTTTTTTATTTATACTCAATGAAAATCAAAGAGCAAACTAGGAAGCTAGCCGCAGGTTGCTCAAAACACTGTT

TTGAGGTTGTAGACGAAACTGACGAAGTCAGCTCAAAACATGTTTTTGAGGTTGTAGATGAAACTGACGAAGTCA GCTCAAAACACTGTTTTGAGGTTGTAGATGAAACTGACGAAGTCAGCTCAAAACACTGTTTTGAGGTTGTAGATG AAACTGACGAAGTCAGCTCAAAACATGTTTTTGAGGTTGTAGATGAAACTGACGAAGTCAGTAACCATACATACG GTAGGGCGACGCTGACGTGGTTTGAAGAGATTTTCGAAGAGTATTAA

MFFYLYSMKIKEQTRKLAAGCSKHCFEVVDETDEVSSKHVFEVVDETDEVSSKHCFEVVDETDEVSSKHCFEVVDETD EVSSKHVFEVVDETDEVSNHTYGRATLTWFEEIFEEYZ

ID47 1260bp

ATGCAGAATCTGAAATTTGCCTTTTCATCTATCATGGCTCACAAGATGCGTTCTTTGCTTACTATGATTGGGATTAT TATCGGTGTTTCATCAGTTGTTGTGATTATGGCTTTGGGTGATTCCCTATCTCGTCAAGTCAATAAAGATATGACTA AATCTCAGAAAAATATTAGCGTCTTTrTCTCTCCTAAAAAAAGTAAAGACGGGTCTTTTACTCAGAAACAATCAGC TTTTACGGTTTCTGGAAAGGAAGAGGAAGTTCCTGTTGAACCGCCAAAACCGCAAGAATCCTGGGTCCAAGAGGC AGCTAAACTGAAGGGAGTGGATAGTTACTATGTAACCAATTCAACGAATGCCATCTTGACCTATCAAGATAAAAA

GGTTGAGAATGCTAATTTGACAGGTGGAAACAGAACTTACATGGACGCTGTTAAGAATGAAATTATTGCAGGTCG TAGTCTGAGAGAGCAAGATTTCAAAGAGTTTGCAAGTGTCATTTTGCTAGATGAGGAATTGTCCATTAGTTTATTT GAATCTCCTCAAGAGGCTATTAACAAGGTTGTAGAAGTCAATGGATTTAGTTACCGGGTCATTGGGGTTTATACTA GTCCGGAGGCTAAAAGATCAAAAATATATGGGTTTGGTGGCTTGCCTATTACTACCAATATCTCCCTTGCTGCGAA TTTTAATGTAGATGAAATAGCTAATATTGTCTTTCGAGTGAATGATACCAGTTTAACCCCAACTCTGGGTCCAGAA

CTGGCACGAAAAATGACAGAGCTTGCAGGCTTACAACAGGGAGAATACCAGGTGGCAGATGAGTCCGTTGTATTT GCAGAAATTCAACAATCGTTTAGTTTTATGACGACGATTATTAGTTCCATCGCAGGGATTTCTCTCTTTGTTGGAG GAACTGGTGTCATGAACATCATGCTGGTTTCGGTGACAGAGCGCACTCGTGAGATTGGTCTTCGTAAGGCTTTGGG TGCAACACGTGCCAATATTTTAATTCAGTTTTTGATTGAATCCATGATTTTGACCTTGTTAGGTGGCTTAATTGGCT TGACAATTGCAAGTGGTTTAACTGCCTTAGCAGGTTTGTTACTGCAAGGTTTAATAGAAGGTATAGAAGTTGGAGT

ATCAATCCCAGTCGCCCTATTTAGTCTTGCAGTTTCGGCTAGTGTTGGTATGATTTTTGGAGTCTTGCCAGCCAAC AAGGCATCGAAACTTGATCCAATTGAAGCCCTTCGTTATGAATGA

MQNLKFAFSSIMAHKMRSLLTMIGIIIGVSSVVVIMALGDSLSRQVNKDMTKSQKNISVFFSPK SKDGSFTQKQSAFTVS GKEEEVPVEPP PQESWVQEAAKLKGVDSYYVTNSTNAILTYQDKKVENANLTGGNRTYMDAVKNEIIAGRSLREQDF

KEFASVILLDEELSISLFESPQEAINKVVEVNGFSYRVIGVYTSPEAKRSKIYGFGGLPITTNISLAANFNVDEIANIVFRVN DTSLTPTLGPELARKMTELAGLQQGEYQVADESVVFAEIQQSFSFMTTIISSIAGISLFVGGTGVMNI LVSVTERTREIG LRKALGATRAMLIQFLIESMILTLLGGUGLTIASGLTALAGLLLQG IEGIEVGVSIPVALFSLAVSASVGMIFGVLPANK ASKLDPIEALRYEZ

ID48 705bp

CTGATGAAGCAACTAATTAGTCTAAAAAATATCTTCAGAAGTTACCGTAATGGTGACCAAGAACTGCAGGTTCTC

AAAAATATCAATCTAGAAGTGAATGAGGGTGAATTTGTAGCCATCATGGGACCATCTGGGTCTGGTAAGTCCACT CTGATGAATACGATTGGCATGTTGGATACACCAACCAGTGGAGAATATTATCTTGAAGGTCAAGAAGTGGCTGGG CTTGGTGAAAAACAACTAGCTAAGGTCCGTAACCAACAAATCGGTTTTGTCTTTCAGCAGTTCTTTCTTCTATCGA AGCTCAATGCTCTGCAAAATGTAGAATTGCCCTTGATTTACGCAGGAGTTTCGTCTTCAAAACGTCGCAAGTTGGC TGAGGAATATTTAGACAAGGTTGAATTGACAGAACGTAGTCACCATTTACCTTCAGAATTATCTGGTGGTCAAAA GCAACGTGTAGCCATTGCGCGTGCCTTGGTAAACAATCCTTCTATTATCCTAGCGGATGAACCGACAGGAGCCTTG GATACCAAAACAGGTAACCAAATTATGCAATTATTGGTTGATTTGAATAAAGAAGGAAAAACCATTATCATGGTA

ACGCATGAGCCTGAGATTGCTGCCTATGCCAAACGTCAGATTGTCATTCGGGATGGGGTCATTTCGTCTGACAGTG CTCAGTTAGGAAAGGAGGAAAACTAA

MMKQLISLKNIFRSYRNGDQE QVLKNINLEVNEGEFVAIMGPSGSG STLMNTIGMLDTPTSGEYYLEGQEVAGLGEK QLAKVRNQQIGFVFQQFFLLS LNALQNVELPLIYAGVSSSKRRKLAEEYLDKVELTERSHHLPSELSGGQKQRVAIARA

LVNNPSIILADEPTGALDTKTGNQIMQLLVDLNKEGKTIIMVTHEPEIAAYAKRQIVIRDGVISSDSAQLG EENZ

ID49 1200bp ATGAAGAAAAAGAATGGTAAAGCTAAAAAGTGGCAACTGTATGCAGCAATCGGTGCTGCGAGTGTAGTTGTATTG

GGTGCTGGGGGGATTTTACTCTTTAGACAACCTTCTCAGACTGCTCTAAAAGATGAGCCTACTCATCTTGTTGTTG CCAAGGAAGGAAGCGTGGCCTCCTCTGTTTTATTGTCAGGGACAGTAACAGCAAAAAATGAACAATATGTTTATT TTGATGCTAGTAAGGGTGATTTAGATGAAATCCTTGTTTCTGTGGGCGATAAGGTCAGCGAAGGGCAGGCTTTAGT CAAGTACAGTAGTTCAGAAGCGCAGGCGGCCTATGATTCAGCTAGTCGAGCAGTAGCTAGGGCAGATCGTCATAT CAATGAACTCAATCAAGCACGAAATGAAGCCGCTTCAGCTCCGGCTCCACAGTTACCAGCGCCAGTAGGAGGAGA

AGATGCAACGGTGCAAAGCCCAACTCCAGTGGCTGGAAATTCTGTTGCTTCTATTGACGCTCAATTGGGTGATGCC CGTGATGCGCGTGCAGATGCTGCGGCGCAATTAAGCAAGGCTCAAAGTCAATTGGATGCAACAACTGTTCTCAGT ACCCTAGAGGGAACTGTGGTCGAAGTCAATAGCAATGTTTCTAAATCTCCAACAGGGGCGAGTCAAGTTATGGTT CATATTGTCAGCAATGAAAATTTACAAGTCAAGGGAGAATTGTCTGAGTACAATCTAGCCAACCTTTCTGTAGGTC AAGAAGTAAGCTTTACTTCTAAAGTGTATCCTGATAAAAAATGGACTGGGAAATTAAGCTATATTTCTGACTATCC

TAAAAACAATGGTGAAGCAGCTAGTCCAGCAGCCGGGAATAATACAGGTTCTAAATACCCTTATACTATTGATGT GACAGGCGAGGTTGGTGATTTGAAACAAGGTTTTTCTGTCAACATTGAGGTΓAAAAGCAAAACTAAGGCTATTCTT GTTCCTGTTAGCAGTCTAGTAATGGATGATAGTAAAAATTATGTCTGGATTGTGGATGAACAACAAAAGGCTAAA AAAGT GAGGTTTCATTGGGAAATGCTGACGCAGAAAATCAAGAAATCACTTCTGGTTTAACGAACGGTGCTAAG GTCATCAGTAATCCAACATCTTCCTTGGAAGAAGGAAAAGAGGTGAAGGCTGATGAAGCAACTAATTAG

MKKKNGKAKKWQLYAAIGAASWVLGAGGILLFRQPSQTALKDEPTHLVVA EGSVASSVLLSGTVTAKNEQYVYFD ASKGDLDEILVSVGDKVSEGQALVKYSSSEAQAAYDSASRAVARADRHINELNQARNEAASAPAPQLPAPVGGEDATV QSPTPVAGNSVASIDAQLGDARDARADAAAQLSKAQSQLDATTVLSTLEGTVVEVNSNVSKSPTGASQVMVHIVSNEN LQVKGELSEYNLANLSVGQEVSFTSKVYPDKKWTGKLSYISDYPKNNGEAASPAAGNNTGSKYPYTIDVTGEVGDLKQ

GFSVNIEVKSKTKAILVPVSSLVMDDSKNYVWIVDEQQKA KVEVSLGNADAENQETTSGLTNGAKVISNPTSSLEEGKE VKADEATNZ

ID50 759bp

ATGTCACGTAAACCATTTATCGCTGGTAACTGGAAAATGAACAAAAATCCAGAAGAAGCTAAAGCATTCGTTGAA GCAGTTGCATCAAAACTTCCTTCATCAGATCTTGTTGAAGCAGGTATCGCTGCTCCAGCTCTTGATTTGACAACTG TTCTTGCTGTTGCAAAAGGCTCAAACCTTAAAGTTGCTGCTCAAAACTGCTACTTTGAAAATGCAGGTGCTTTCAC TGGTGAAACTAGCCCACAAGTTTTGAAAGAAATCGGTACTGACTACGTTGTTATCGGTCACTCAGAACGCCGTGA CTACTTCCATGAAACTGATGAAGATATCAACAAAAAAGCAAAAGCAATCTTTGCGAACGGTATGCTTCCAATCAT

CTGTTGTGGTGAATCACTTGAAACTTACGAAGCTGGTAAAGCTGCTGAATTCGTAGGTGCTCAAGTATCTGCTGCA TTGGCTGGATTGACTGCTGAACAAGTTGCTGCCTCAGTTATCGCTTATGAGCCAATCTGGGCTATCGGTACTGGTA AATCAGCTTCACAAGACGATGCACAAAAAATGTGTAAAGTTGTTCGTGACGTTGTAGCTGCTGACTTTGGTCAAG AAGTCGCAGACAAAGTTCGTGTTCAATACGGTGGTTCTGTTAAACCTGAAAATGTTGCTTCATACATGGCTTGCCC AGACGTTGACGGTGCCCTTGTAGGTGGTGCGTCACTTGAAGCTGAAAGCTTCTTGGCTTTGCTTGACTTTGTAAAA

TAA

MSRKPFIAGNW MNKNPEEA AFVEAVAS LPSSDLVEAGIAAPALDLTTVLAVAKGSNLKVAAQNCYFENAGAFTG ETSPQVLKEIGTDYVVIGHSERRDYFHETDEDINK AKAIFANGMLPIICCGESLETYEAGKAAEFVGAQVSAALAGLTA EQVAASVIAYEPIWAIGTGKSASQDDAQKMCKVVRDVVAADFGQEVADKVRVQYGGSVKPENVASYMACPDVDGAL

VGGASLEAESFLALLDFVKZ

ID51 1473bp TTGAAAACAAAAATTGGATTAGCAAGTATCTGTTTACTAGGCTTGGCAACTAGTCATGTCGCTGCAAATGAAACTG

AAGTAGCAAAAACTTCGCAGGATACAACGACAGCTTCAAGTAGTTCAGAGCAAAATCAGTCTTCTAATAAAACGC AAACGAGCGCAGAAGTACAGACTAATGCTGCTGCCCACTGGGATGGGGATTATTATGTAAAGGATGATGGTTCTA AAGCTCAAAGTGAATGGATTTTTGACAACTACTATAAGGCTTGGTTTTATATTAATTCAGATGGTCGTTACTCGCA GAATGAATGGCATGGAAATTACTACCTGAAATCAGGTGGATATATGGCCCAAAACGAGTGGATCTATGACAGTAA TTACAAGAGTTGGTTTTATCTCAAGTCAGATGGGGCTTATGCTCATCAAGAATGGCAATTGATTGGAAATAAGTGG TACTACTTCAAGAAGTGGGGTTACATGGCTAAAAGCCAATGGCAAGGAAGTTATTTCTTGAATGGTCAAGGAGCT ATGATGCAAAATGAATGGCTCTATGATCCAGCCTATTCTGCTTATTTTTATCTAAAATCCGATGGAACTTATGCTA ACCAAGAGTGGCAAAAAGTGGGCGGCAAATGGTACTATTTCAAGAAGTGGGGCTATATGGCTCGGAATGAGTGGC AAGGCAACTACTATTTGACTGGAAGTGGTGCCATGGCGACTGACGAAGTGATTATGGATGGTACTCGCTATATCTT TGCGGCCTCTGGTGAGCTCAAAGAAAAAAAAGATTTGAATGTCGGCTGGGTTCACAGAGATGGTAAGCGCTATTT

CTTTAATAATAGAGAAGAACAAGTGGGAACCGAACATGCTAAGAAAGTCATTGATATTAGTGAGCACAATGGTCG TATCAATGATTGGAAAAAGGTTATTGATGAGAACGAAGTGGATGGTGTCATTGTTCGTCTAGGTTATAGCGGTAA AGAAGACAAGGAATTGGCGCATAACATTAAGGAGTTAAACCGTCTGGGAATTCCTTATGGTGTCTATCTCTATAC CTATGCTGAAAATGAGACCGTGCTGAGAGTGACGCTAAACAGACCATTGAACTTATAAAGAAATACAATATGAAC CTGTCTTACCCTATCTATTATGATGTTGAGAATTGGGAATATGTAAATAAGAGCAAGAGAGCTCCAAGTGATACA

GGCACTTGGGTTAAAATCATCAACAAGTACATGGACACGATGAAGCAGGCGGGTTATCAAAATGTGTATGTCTAT AGCTATCGTAGTTTATTACAGACGCGTTTAAAACACCCAGATATTTTAAAACATGTAAACTGGGTAGCGGCCTATA CGAATGCTTTAGAATGGGAAAACCCTCATTATTCAGGAAAAAAAGGTTGGCAATATACCTCTTCTGAATACATGA AAGGAATCCAAGGGCGCGTAGATGTCAGCGTTTGGTATTAA

MKTKIGLASICLLGLATSHVAANETEVAKTSQDTTTASSSSEQNQSSNKTQTSAEVQTNAAAHWDGDYYVKDDGSKAQ SEWIFDNYYKAWFYINSDGRYSQNEWHGNYYLKSGGYMAQNEWIYDSNYKSWFYLKSDGAYAHQEWQLIGNKWYY FKKWGYMAKSQWQGSYFLNGQGAMMQNEWLYDPAYSAYFYLKSDGTYANQEWQKVGGKWYYFKKWGYMARNE WQGNYYLTGSGAMATDEVIMDGTRYIFAASGELKEKKDLNVGWVHRDGKRYFFNNREEQVGTEHAKKVIDISEHNG RINDW KVIDENEVDGVIVRLGYSGKEDKELAHNIKELNRLGIPYGVYLYTYAENETDAESDAKQTIELIKKYNMNLSY

PIYYDVENWEYVNKSKRAPSDTGTWV IINKYMDTMKQAGYQNVYVYSYRSLLQTRLKHPDILKHVNWVAAYTNAL EWENPHYSGKKGWQYTSSEYMKGIQGRVDVSVWYZ

ID52 774bp

ATGAAAAAATTTGCCAACCTTTATCTGGGACTGGTCTTTCTGGTCCTCTACCTGCCTATCTTTTACTTGATTGGCTA TGCCTTTAATGCTGGTGATGATATGAATAGCTTTACAGGTTΓTAGCTGGACTCACΓTTGAAACCATGTTTGGAGAT GGGAGACTCATGCTGATTTTGGCTCAGACATTTTTCTTGGCCTTCCTATCAGCCTTGATAGCGACCATTATCGGGA CΠ TTGGTGCCATTTACATCTACCAGTCTCGTAAGAAATACCAAGAAGCCTTTCTATCACTCAATAATATCCTCAT GGTTGCGCCTGACGTTATGATTGGTGCTAGCTTCTTGATTCTCTTTACCCAACTCAAGTTTTCACTTGGCTTTTTGA CCGTTCTATCTAGTCACGTGGCCTTCTCCATTCCTATCGTGGTCTTGATGGTCTTGCCTCGACTCAAGGAAATGAA TGGCGACATGATTCATGCGGCCTATGACTTGGGAGCTAGTCAATTTCAGATGTTCAAGGAAATCATGCTTCCTTAC CTGACTCCGTCTATCATTACTGGTTATTTCATGGCCTTCACCTATTCGTTAGATGACTTTGCCGTGACCTTCTTTGT AACAGGAAATGGCTTTTCAACCCTATCAGTCGAGATTTACTCTCGTGCTCGCAAGGGGATTTCCTTAGAAATCAAT GCCCTGTCTGCTCTAGTCTTTCTCTTTAGTATTATCCTAGTTGTAGGTTATTACTTTATCTCTCGTGAGAAGGAGGA

GCAAGCATGA

MKKFANLYLGLVFLVLYLPIFYLIGYAFNAGDDMNSFTGFSWTHFETMFGDGRLMLILAQTFFLAFLSALIATΠGTFGA IYIYQSR KYQEAFLSLNNILMVAPDVMIGASFLILFTQLKFSLGFLTVLSSHVAFSIPΓVVLMVLPRLKEMNGDMIHAAY DLGASQFQMF EIMLPYLTPSΠTGYFMAFTYSLDDFAVTFFVTGNGFSTLSVEIYSRARKGISLEINALSALVFLFSΠLVV

GYYFISREKEEQAZ

ID59 1071bp ATGAAAAAAATCTATTCATTTTTAGCAGGAATTGCAGCGATTATCCTTGTCTTGTGGGGAATTGCGACTCATTTAG

ATAGTAAAATCAATAGTCGAGATAGTCAAAAATTGGTTATCTATAACTGGGGAGACTATATCGATCCTGAACTCTT GACTCAGTTTACAGAAGAAACAGGAATTCAAGTTCAGTACGAGACTTTTGACTCCAACGAAGCCATGTACACTAA GATAAAGCAGGGTGGAACGACCTACGATATTGCCATTCCAAGTGAATACATGATTAACAAGATGAAGGACGAAG ACCTCΓTGGTTCCGCTTGATTATTCAAAAATTGAAGGAATCGAAAATATCGGACCAGAGTTTCTCAACCAGTCCTT TGACCCAGGTAATAAATTCTCCATCCCTTACTTCTGGGGAACCTTAGGAATTGTCTACAACGAAACCATGGTAGAT GAAGCGCCTGAGCATTGGGATGACCTTTGGAAGCCGGAGTATAAGAATTCTATCATGCTCTTTGATGGGGCGCGT GAGGTGCTGGGACTAGGACTCAATTCCCTCGGCTACAGCCTCAACTCCAAGGATCTGCAGCAGTTGGAAGAGACA GTGGATAAGCTCTACAAACTGACTCCAAATATCAAGGCTATCGTTGCGGACGAGATGAAGGGCTATATGATTCAG AATAATGTTGCAATCGGCGTGACCTTCTCTGGTGAAGCCAGCCAAATGTTAGAAAAAAATGAAAATCTACGTTAT GTGGTACCGACAGAGGCCAGCAATCTTTGGTTTGACAATATGGTCATTCCCAAAACAGTTAAAAACCAAAACTCA

GCCTATGCCTTTATCAACTTTATGTTGAAACCTGAAAATGCTCTCCAAAATGCGGAGTATGTCGGCTATTCAACAC CAAACCTACCAGCGAAGGAATTGCTCCCAGAGGAAACAAAGGAAGATAAGGCCTTCTATCCCGATGTTGAAACCA TGAAACACCTAGAAGTTTATGAGAAATTTGACCATAAATGGACAGGGAAATATAGCGACCTCTTCCTACAGTTTA AAATGTATCGGAAGTAG

MKKIYSFLAGIAAΠLVLWGIATHLDSKINSRDSQKLVIYNWGDYIDPELLTQFTEETGIQVQYETFDSNEAMYTKIKQGG TTYDIAIPSEYMINKMKDEDLLVPLDYSKIEGIENIGPEFLNQSFDPGNKFSIPYFWGTLGIVYNETMVDEAPEHWDDLW KPEYKNSIMLFDGAREVLGLGLNSLGYSLNSKDLQQLEETVDKLY LTPNIKAIVADEMKGYMIQNNVAIGVTFSGEAS QMLEKNENLRYVVPTEASNLWFDNMVIPKTVKNQNSAYAFINFMLKPENALQNAEYVGYSTPNLPAKELLPEETKED KAFYPDVETMKHLEVYEKFDHKWTGKYSDLFLQFKMYRKZ ID61 1851bp

ATGAATAAAAAACTAACAGATTATGTGATTGATCTGGTGGAAATTTTAAATAAACAACAAAAGCAGGTTTTCTGG GGAATATTTGATATTTTCAGTATGGTGGTTTCCATCATTGTATCTTATATTTTATTTTATGGGCTGATTAATCCAGC

ACCTGTTGACTACATTATCTATACGAGTTTGGCCTTCCTGTTCTATCAATTGATGATRGGTTTTTGGGGGTTGAACG CGAGCATTAGTCGTTACAGCAAGATTACGGATTTCATGAAAATCTTTTTTGGTGTGACTGCTAGCAGTGTCTTGTC ATATAGTATCTGTTATGCCTTCTTGCCACTCTTCTCCATCCGTTTCATCATTCTCTTTATCTTGTTGAGTACCTTCTT GATTTTATTGCCACGGATTACTTGGCAGTTAATCTACTCCAGACGCAAAAAAGGTAGTGGTGATGGAGAACACCG TCGGACCTTCTTGATTGGTGCCGGTGATGGTGGGGCTCTTTTTATGGATAGTTACCAACATCCAACCAGTGAATTA

GAACTGGTCGGTATTTΓGGATAAGGATTCTAAGAAAAAGGGTCAAAAACTTGGTGGTATTCCTGTTTTGGGCTCTT ATGACAATCTGCCTGAATTAGCCAAACGCCATCAAATCGAGCGTGTCATCGTTGCGATTCCGTCGCTGGATCCGTC AGAATATGAGCGTATCTTGCAGATGTGTAATAAGCTGGGTGTCAAATGTTACAAGATGCCTAAGGTTGAAACTGT TGTTCAGGGCCTTCACCAAGCAGGTACTGGCTTCCAAAAAATTGATATTACGGACCTTTTGGGTCGTCAGGAAATC CGTCTTGACGAATCGCGTCTGGGTGCAGAACTGACAGGTAAGACCATCTTAGTCACAGGAGCTGGAGGTTCAATC

GGTTCTGAAATCTGTCGTCAAGTTAGTCGCTTCAATCCTGAACGCATTGTCTTGCTCGGTCATGGGGAAAACTCAA TCTACC TGTTTATCATGAATTGATTCGTAAGTTCCAAGGGATTGATTATGTACCTGTGATTGCGGACATTCAAGA CTATGATCGTTTGT GCAAGTCTTTGAGCAGTACAAACCTGCTATTGTTTATCATGCGGCAGCCCACAAGCATGTT CCTATGATGGAGCGCAATCCAAAAGAAGCCTTCAAAAACAATATCCGTGGAACTTACAATGTTGCTAAGGCTGTT GATGAAGCTAAAGTGTCTAAGATGGTTATGATTTCGACAGATAAGGCAGTCAATCCACCAAATGTTATGGGAGCA ACCAAGCGCGTGGCGGAGTTGATTGTCACTGGCTTTAACCAACGTAGCCAATCAACCTACTGTGCAGTTCGTTTTG GGAATGTTCTTGGTAGCCGTGGTAGTGTCATTCCAGTCTTTGAACGTCAGATTGCTGAAGGTGGGCCTGTAACGGT GACAGACTTCCGTATGACCCGTTACTTTATGACCATTCCAGAAGCTAGCCGTCTGGTTATCCATGCTGGTGCTTAT GCCAAAGATGGGGAAGTCTTTATCCTTGATATGGGCAAACCAGTCAAGATTTATGACTTGGCCAAGAAGATGGTG CTTCTAAGTGGCCACACTGAAAGTGAAATTCCAATCGTTGAAGTTGGAATCCGCCCAGGTGAAAAACTCTACGAA

GAACTCTTGGTATCAACCGAACTCGTTGATAATCAAGTTATGGATAAGATTTTCGTTGGTAAGGTTAATGTCATGC CTTTAGAATCCATCAATCAAAAGATTGGAGAGTTCCGCACTCTCAGTGGAGATGAGTTGAAGCAAGCTATTATCG CCTTTGCTAATCAAACAACCCACATTGAATAA MNKKLTDYVIDLVEILNKQQKQVFWGIFDIFSMVVSIIVSYILFYG INPAPVDYIIYTSLAFLFYQLMIGFWGLNASISRY SKITDFMKIFFGVTASSVLSYSICYAFLPLFSIRFIILFILLSTFLILLPRITWQLIYSRRKKGSGDGEHRRTFLIGAGDGGALF MDSYQHPTSELELVGILDKDSKKKGQKLGGIPVLGSYDNLPELAKRHQIERVIVAIPSLDPSEYERILQMCNKLGVKCYK MPKVETVVQGLHQAGTGFQKIDITDLLGRQEIRLDESRLGAELTGKTILVTGAGGSIGSEICRQVSRFNPERIVLLGHGEN SIYLVYHELIRKFQGIDYVPVIADIQDYDRLLQVFEQYKPAIVYHAAAHKHVPMMERNPKEAFKNNIRGTYNVAKAVD EAKVSKMVMISTDKAVNPPNVMGATKRVAELIVTGFNQRSQSTYCAVRFGNVLGSRGSVIPVFERQIAEGGPVTVTDFR

MTRYFMTIPEASRLVIHAGAYAKDGEVFILDMGKPVKIYDLAKKMVLLSGHTESEIPIVEVGIRPGEKLYEELLVSTELV DNQVMDKIFVGKVNVMPLESINQKIGEFRTLSGDELKQAIIAFANQTTHIEZ

ID101 1338bp

ATGAT GAACTTTATGATAGTTACAGTCAAGAAAGTCGAGATTTACATGAAAGTCTAGTCGCTACTGGTCTTTCTC AACTTGGAGTGGTCATCGATGCAGATGGTTTTCTGCCTGATGGTCTGCTTTCTCCTTTTACCTATTATCTAGGTTAC GAGGATGGAAAACCTCTCTATTTTAATCAAGTTCCCGTTTCAGATTTTTGGGAAATTTTAGGAGATAATCAGTCTG CTTGTATTGAAGATGTGACGCAGGAGAGGGCTGTCATTCATTATGCTGATGGAATGCAGGCTCGCTTGGTTAAACA GGTAGACTGGAAAGACCTAGAAGGTCGAGTACGTCAGGTTGACCACTACAATCGCTTCGGAGCTTGTTTTGCTAC

AACGACTTATAGCGCAGATAGCGAGCCGATTATGACAGTTTACCAAGATGTCAATGGTCAACAAGTTTTACTGGA AAACCATGTGACGGGTGATATCTTATTGACTTTGCCAGGTCAGTCCATGCGTTACTTTGCAAATAAAGTTGAATTT ATCACCTTCTTTTTGCAAGATTTGGAAATAGATACCAGTCAGCTTATCTTTAATACTCTAGCGACTCCTTTCTTGGT TTCCTTCCATCATCCAGATAAATCTGGCTCGGATGTCTTGGTATGGCAGGAACCTCTCTATGATGCCATTCCAGGT AATATGCAGTTGATTTTGGAAAGTGATAATGTGCGTACTAAGAAGATCATCATTCCAAATAAGGCGACTTATGAG

CGCGCTTTAGAGTTAACTGACGAGAAATACCATGATCAGTTTGTGCACTTGGGTTATCATTACCAGTTCAAACGTG ATAATTTCCTAAGACGAGATGCCTTAATCTTGACCAATTCAGATCAGATTGAGCAAGTAGAAGCAATCGCAGGAG CCTTGCCTGATGTCACTTTCCGTATTGCAGCGGTGACAGAGATGTCTTCTAAGCTCTTAGACATGCTTTGCTATCCT AATGTGGCCCTTTACCAGAACGCTAGTCCACAGAAGATTCAGGAGCTGTATCAACTGTCGGATATTTACTTGGATA TAAACCACAGTAATGAGTTGCTACAGGCAGTGCGTCAGGCCTTTGAGCACAATCTCTTGATTCTTGGCTTTAATCA

GACGGTGCACAATAGACTTTATATCGCTCCAGACCATCTATTTGAAAGTAGTGAAGTTGCTGCTTTGGTTGAGACC ATTAAATTGGCCCTTTCAGATGTTGATCAAATGCGTCAGGCACTTGGCAAACAAGGCCAACATGCAAATTATGTTG ACTTGGTGAGATATCAGGAAACCATGCAAACTGTTTTAGGAGGCTAA MIELYDSYSQESRDLHESLVATGLSQLGVVIDADGFLPDGLLSPFTYYLGYEDGKPLYFNQVPVSDFWEILGDNQSACIE

DVTQERAVIHYADGMQARLVKQVDWKDLEGRVRQVDHYNRFGACFATTTYSADSEPIMTVYQDVNGQQVL ENHV TGDILLTLPGQSMRYFANKVEFITFFLQDLEIDTSQLIFNTLATPFLVSFHHPDKSGSDVLVWQEPLYDAIPGN QLILES DNVRTKKIIIPNKATYERALELTDEKYHDQFVHLGYHYQFKRDNFLRRDALILTNSDQIEQVEAIAGALPDVTFRIAAVT EMSSKLLDMLCYPNVALYQNASPQKIQELYQLSDIYLDINHSNELLQAVRQAFEHNLLILGFNQTVHNRLYIAPDHLFE SSEVAALVETIKLALSDVDQMRQALGKQGQHANYVDLVRYQETMQTVLGGZ

SUBSTΓΓUTE SHEET (RULE 26) ID102 1512bp

ATGACAATTTACAATATAAATTTAGGAATTGGTTGGGCTAGTAGCGGTGTTGAATACGCTCAAGCCTATCGTGCTG GTGTTTTTCGGAAATTAAATCTGTCCTCTAAGTTTATCTTTACAGATATGATTTTAGCCGATAATATTCAGCACTTA

ACAGCCAATATTGGTTTTGATGATAATCAGGTTATCTGGCTTTATAATCATTTCACAGATATCAAAATTGCACCTA CTAGCGTGACAGTGGATGATGTCTTGGCTTACTTTGGTGGTGAAGAAAGTCACAGAGAAAAAAATGGCAAGGTTT TACGTGTATTCTTTTTTGACCAAGATAAGTTTGTAACCTGTTATTTGGTTGATGAGAACAAGGACTTGGTTCAACA TGCCGAGTATGTΓΓΓTAAGGGAAACCTGATTCGGAAGGATTACTTTTCTTATACGCGTTATTGTAGCGAGTATTTT GCTCCCAAGGACAATGTTGCAGTCTTATACCAACGAACTTTTTATAATGAAGACGGGACTCCAGTCTATGATATCT

TGATGAATCAAGGGAAGGAAGAAGTTTATCATTTCAAGGATAAGATTTTCTATGGAAAGCAAGCTTTTGTGCGTG CCTTTATGAAATCTTTGAATTTGAATAAGTCTGATTTGGTCATTCTCGATAGGGAGACAGGTATTGGACAGGTTGT GTTTGAGGAAGCACAGACAGCACATCTAGCGGTAGTTGTTCATGCGGAGCATTATAGTGAAAATGCTACAAATGA GGACTATATCCTTTGGAATAACTATTATGACTATCAGTTTACCAATGCAGATAAGGTTGACTTCTTTATCGTGTCT ACTGATAGACAAAATGAAGTTCTACAAGAGCAATTTGCCAAATATACTCAGCATCAGCCAAAGATTGTTACCATT

CCTGTAGGCAGTATTGATΓCCTTGACAGATTCAAGTCAAGGGCGCAAACCATTTΓCATTGATTACGGCTTCACGTC TTGCCAAAGAAAAGCACATTGATTGGCTTGTGAAAGCTGTGATTGAAGCTCATAAGGAGTTACCGGAACTAACCT TTGATATCTATGGTAGTGGTGGAGAAGATTCTCTGCTTAGAGAAATTATTGCAAATCATCAGGCAGAGGACTATAT CCAACTCAAGGGGCATGCGGAACTTTCGCAGATTTATAGCCAGTATGAGGTCTACTTAACGGCTTCTACCAGCGA AGGATTTGGTCTGACCTTGATGGAAGCTATTGGTTCAGGTCTACCTCTAARRGGTTTTGATGTGCCTTATGGTAATC

AGACCTTTATAGAGGATGGGCAAAATGGTTATTTGATRCCAAGTTCATCTGACCATGTAGAAGACCAAATCAAGC AAGCTTATGCCGCTAAGATTTGTCAATTGTATCAAGAAAATCGTTTGGAAGCTATGCGTGCCTATTCTTACCAAAT TGCAGAAGGCTTCTTGACCAAAGAAATTTTAGAAAAGTGGAAGAAAACAGTAGAGGAGGTGCTCCATGATTGA MTIYNINLGIGWASSGVEYAQAYRAGVFRKLNLSSKFIFTDMILADNIQHLTANIGFDDNQVIWLYNHFTDIKIAPTSVT

VDDVLAYFGGEESHREKNGKVLRVFFFDQDKFVTCYLVDENKDLVQHAEYVFKGNLIRKDYFSYTRYCSEYFAPKDN VAVLYQRTFYNEDGTPVYDILMNQGKEEVYHFKDKIFYGKQAFVRAFMKSLNLNKSDLVILDRETGIGQVVFEEAQTA HLAVVVHAEHYSENATNEDYILWNNYYDYQFTNADKVDFFIVSTDRQNEV QEQFAKYTQHQPKIVTIPVGSIDSLTDS SQGRKPFSLITASRLAKE HIDWLVKAVIEAHKELPELTFDIYGSGGEDSLLREIIANHQAEDYIQLKGHAELSQIYSQYE VYLTASTSEGFGLTLMEAIGSGLPLIGFDVPYGNQTFIEDGQNGYLIPSSSDHVEDQIKQAYAAKICQLYQENRLEAMRA

YSYQIAEGFLTKEILEKWKKTVEEVLHDZ

ID103 2292bp

ATGTCCTCTCTTTCGGATCAAGAATTAGTAGCTAAAACAGTAGAGTTTCGTCAGCGTCTTTCCGAGGGAGAAAGTC TAGACGATATTTTGGTTGAAGCTTTTGCTGTGGTGCGTGAAGCAGATAAGCGGATTTTAGGGATGTTTCCTTATGA

TGTTCAAGTCATGGGAGCTATTGTCATGCACTATGGAAATGTTGCTGAGATGAATACGGGGGAAGGTAAGACCTT GACAGCTACCATGCCTGTCTATTTGAACGCTTΓTTCAGGAGAAGGAGTGATGGTTGTGACTCCTAATGAGTATTTA TCAAAGCGTGATGCCGAGGAAATGGGTCAAGTTTATCGTTTTCTAGGATTGACCATTGGTGTACCATTTACGGAAG ATCCAAAGAAGGAGATGAAAGCTGAAGAAAAGAAGCTTATCTATGCTTCGGATATCATCTACACAACCAATAGTA ATTTAGGTTTTGATTATCTAAATGATAACCTAGCCTCGAATGAAGAAGGTAAGTTTTTACGACCGTTTAACTATGT

GATTATTGATGAAATTGATGATATCTTGCTTGATAGTGCACAAACTCCTCTGATTATTGCGGGTTCTCCTCGTGTTC AGTCTAATTACTATGCGATCATTGATACACTTGTAACAACCTTGGTCGAAGGAGAGGATTATATCTTTAAAGAGGA GAAAGAGGAGGTTTGGCTCACTACTAAGGGGGCCAAGTCTGCTGAGAATTTCCTAGGGATTGATAATTTATACAA GGAAGAGCATGCGTCΓITTGCTCGTCATTTGGTTTATGCGATTCGAGCTCATAAGCTCTTTACTAAAGATAAGGAC TATATCATTCGTGGAAATGAGATGGTACTGGTTGATAAGGGAACAGGGCGTCTAATGGAAATGACTAAACTTCAA GGAGGTCTCCATCAGGCTATTGAAGCCAAGGAACATGTCAAATTATCTCCTGAGACGCGGGCTATGGCCTCGATC ACCTATCAGAGTCTTTTTAAGATGTTTAATAAGATATCTGGTATGACAGGGACAGGTAAGGTCGCGGAAAAAGAG TTTATTGAAACTTACAATATGTCTGTAGTACGCATTCCAACCAATCGTCCGAGACAACGGATTGACTATCCAGATA ATCTATATATCACTTTACCTGAAAAAGTGTATGCATCCTTGGAGTACATCAAGCAATACCATGCTAAGGGAAATCC TTTACTCGTTTTTGTAGGCTCAGTTGAAATGTCTCAACTCTATTCGTCTCTCTTGTTTCGTGAAGGGATTGCCCATA

ATGTCCTAAATGCTAATAATGCGGCGCGTGAGGCTCAGATTATCTCCGAGTCAGGTCAGATGGGGGCTGTGACAG TGGCTACCTCTATGGCAGGACGTGGTACGGATATCAAGCTTGGTAAAGGAGTCGCAGAGCTTGGGGGCTTGATTG TTATTGGGACTGAGCGGATGGAAAGTCAGCGGATCGACCTACAAATTCGTGGCCGTTCTGGTCGTCAGGGAGATC CTGGTATGAGTAAATTTTTTGTATCCTTAGAGGATGATGTTATCAAGAAATTTGGTCCATCTTGGGTGCATAAAAA GTACAAAGACTATCAGGTTCAAGATATGACTCAACCGGAAGTATTGAAAGGTCGTAAATACCGGAAACTAGTCGA

AAAGGCTCAGCATGCCAGTGATAGTGCTGGACGTTCAGCACGTCGTCAGACTCTGGAGTATGCTGAAAGTATGAA TATACAACGGGATATAGTCTATAAAGAGAGAAATCGTCTAATAGATGGTTCTCGTGACTTAGAGGATGTTGTTGTG GATATCATTGAGAGATATACAGAAGAGGTAGCGGCTGATCACTATGCTAGTCGTGAATTATTGTTTCACTTTATTG TGACCAATATTAGTTTTCATGTTAAAGAGGTTCCAGATTATATAGATGTAACTGACAAAACTGCAGTTCGTAGCTT TATGAAGCAGGTGATTGATAAAGAACTTTCTGAAAAGAAAGAATTACTTAATCAACATGACTTATATGAACAGTT TTTACGACTTTCACTGCTTAAAGCCATTGATGACAACTGGGTAGAGCAGGTAGACTATCTACAACAGCTATCCATG GCTATCGGTGGTCAATCTGCTAGTCAGAAAAATCCAATCGTAGAGTACTATCAAGAAGCCTACGCGGGCTTTGAA GCTATGAAAGAACAGATTCATGCGGATATGGTGCGTAATCTCCTGATGGGGCTGGTTGAGGTCACTCCAAAAGGT GAAATCGTGACTCATTTTCCATAA

MSSLSDQELVAKTVEFRQRLSEGESLDDILVEAFAVVREADKRILGMFPYDVQVMGAIVMHYGNVAEMNTGEGKTLT ATMPVYLNAFSGEGVMVVTPNEYLSKRDAEEMGQVYRFLGLTIGVPFTEDPKKEMKAEE KLIYASDIIYTTNSNLGF DYLNDNLASNEEGKFLRPFNYVIIDEIDDILLDSAQTPLIIAGSPRVQSNYYAIIDTLVTTLVEGEDYIFKEEKEEVWLTTK GAKSAENFLGIDNLYKEEHASFARHLVYAIRAHKLFT DKDYIIRGNEMVLVDKGTGRLMEMTKLQGGLHQAIEA EH VKLSPETRAMASITYQSLFKMFNKISGMTGTGKVAEKEFIETYNMSVVRIPTNRPRQRIDYPDNLYITLPEKVYASLEYIK

QYHAKGNPLLVFVGSVEMSQLYSSLLFREGIAHNVLNANNAAREAQIISESGQMGAVTVATSMAGRGTDIKLGKGVAE LGGLIVIGTERMESQRIDLQIRGRSGRQGDPGMSKFFVSLEDDVIKKFGPSWVHKKYKDYQVQDMTQPEVLKGR YRK LVEKAQHASDSAGRSARRQTLEYAESMNIQRDIVYKERNRLIDGSRDLEDVVVDIIERYTEEVAADHYASRELLFHFIVT NISFHVKEVPDYIDVTDKTAVRSFMKQVIDKELSEK ELLNQHDLYEQFLRLSLLKAIDDNWVEQVDYLQQLSMAIGG QSASQKNPIVEYYQEAYAGFEAMKEQIHADMVRNLLMGLVEVTPKGEIVTHFPZ

ID104 879bp

ATGAAACAAGAATGGTTTGAAAGTAATGATTTTGTAAAAACAACAAGCAAGAACAAGCCTGAAGAGCAAGCTCA AGAGGTTGCAGACAAGGCTGAAGAAAGGATACCCGATCTCGATACACCAATTGAAAAAAATACTCAGTTAGAGG

AGGAAGTCTCTCAAGCTGAAGTCGAATTGGAAAGCCAGCAAGAAGAGAAAATTGAAGCTCCTGAAGACAGTGAA GCGAGAACAGAAATAGAAGAAAAGAAGGCATCTAATTCTACTGAAGAAGAGCCAGACCTTTCTAAAGAAACAGA AAAAGTCACTATAGCTGAAGAGAGCCAAGAAGCTCTTCCTCAGCAAAAAGCAACCACGAAAGAGCCACTTCTTAT CAGTAAATCTTTAGAAAGTCCTTATATCCCCGACCAAGCTCCAAAATCTAGGGATAAATGGAAAGAGCAAGTGCT TGATTTTTGGTCTTGGCTAGTGGAAGCGATCAAATCTCCTACAAGTAAGTTGGAAACAAGTATCACACACAGTTAC

ACAGCCTTTCTCTTGCTCATTCTGTTTTCTGCATCTTCCTTTTTCTTTAGTATCTATCACATCAAACATGCTTACTAT GGACATATAGCAAGCATΓAACAGTCGCTTCCCTGAGCAGCTAGCTCCTTTAACTCTTTTTTCTATCATCTCTATCCT AGTAGCGACAACACTCTTCTTCTTTTCATTCCTCTTGGGTAGTTTCGTTGTGAGACGATTTATCCACCAGGAAAAG GACTGGACGCTAGACAAGGTTCTCCAACAATATAGTCAACTCTTGGCAATTCCAATCTCCTCACTGCTATTGCTAG TTTCTTTGCTTTCTTTGATAGCCTACGATTTACAGCCCTCTTGTGTGTGA

MKQEWFESNDFV TTSKNKPEEQAQEVADKAEERIPDLDTPIEKNTQLEEEVSQAEVELESQQEEKIEAPEDSEARTEIE EKKASNSTEEEPDLSKETEKVTIAEESQEALPQQKATTKEPLLISKSLESPYIPDQAPKSRDKWKEQVLDFWSWLVEAIKS PTSKLETSITHSYTAFLLLILFSASSFFFSIYHIKHAYYGHIASINSRFPEQLAPLTLFSIISILVATTLFFFSFLLGSFVVRRFIH QEKDWTLDKVLQQYSQLLAIPISSLLLLVSLLSLIAYDLQPSCVZ

ID106 327bp

ATGTACTTTCCAACATCCTCTGCCTTGATTGAATTTCTCATCTTGGCTGTACTGGAGCAGGGTGATTCTTATGGTTA TGAGATTAGCCAAACCATTAAGCTGATCGCTAATATCAAAGAATCCACACTCTATCCCATTCTCAAAAAATTGGA

AGGCAATAGCTTTCTGACAACCTATTCTAGAGAGTTCCAAGGTCGCATGCGCAAATACTACTCCTTGACAAACGG TGGTATAGAGCAGCTCTTGACCCTAAAAGATGAATGGGCACTCTATACAGACACCATCAATGGCATCATAGAAGG GAGTATCCGCCATGACAAGAACTGA MYFPTSSALIEFLILAV EQGDSYGYEISQTIKLIANIKESTLYPILKKLEGNSFLTTYSREFQGRMRKYYSLTNGGIEQLLT

LKDEWALYTDTINGIIEGSIRHDKNZ

ID108 954bp ATGGATTTTGAAAAAATTGAACAAGCTTATATCTATTTACTAGAGAATGTCCAAGTCATCCAAAGTGATTTGGCGA

CCAACTTTTATGACGCCTTGGTGGAGCAAAATAGCATCTATCTGGATGGTGAAACTGAGCTAAACCAGGTCAAAG ACAACAATCAGGCCCTTAAGCGTTTAGCACTACGCAAAGAAGAATGGCTCAAGACCTACCAGTTTCTCTTGATGA AGGCTGGGCAAACAGAACCCTTGCAGGCCAATCACCAGTTTACACCGGATGCTATTGCTTTGCTTTTGGTGTTTAT TGTGGAAGAGTTGTTTAAAGAGGAGGAAATTACTATCCTCGAAATGGGTTCTGGGATGGGAATTCTAGGCGCTAT TTTCTTGACCTCGCTTACTAAAAAGGTGGATTACTTGGGAATGGAAGTGGATGATTTGCTGATTGATCTGGCAGCT

AGCATGGCAGATGTAATTGGTTTGCAGGCTGGCTTTGTCCAAGGAGATGCCGTTCGCCCACAAATGCTCAAAGAA AGCGATGTGGTCATCAGTGACTTGCCTGTCGGCTATTATCCTGATGATGCCGTTGCGTCGCGCCATCAAGTTGCTT CTAGCCAAGAACATACTTACGCCCATCACTTGCTCATGGAACAAGGGCTTAAGTACCTCAAGTCAGACGGATACG CTATTTTTCTAGCTCCGAGTGATTTGTTGACCAGTCCTCAAAGTGATTTGTTAAAAGAATGGCTGAAAGAAGAGGC GAGTCTGGTTGCTATGATTAGTCTGCCTGAAAATCTCTTTGCTAATGCCAAACAATCTAAGACTATTTTTATCTTAC

AGAAGAAAAATGAAATAGCAGTAGAGCCTTTTGTTTATCCACTTGCTAGCTTGCAAGATGCAAGTGTTTTAATGAA ATTTAAAGAAAATTTTCAAAAATGGACTCAAGGTACTGAAATATAA

MDFEKIEQAYIYLLENVQVIQSDLATNFYDALVEQNSIYLDGETE NQVKDNNQALKRLALRKEEWLKTYQFLLMKA GQTEPLQANHQFTPDAIALLLVFIVEELFKEEEITILEMGSGMGILGAIFLTSLTKKVDYLGMEVDDLLIDLAASMADVI GLQAGFVQGDAVRPQMLKESDVVISDLPVGYYPDDAVASRHQVASSQEHTYAHHLLMEQGLKYLKSDGYAIFLAPSD

LLTSPQSD LKEWLKEEASLVAMISLPENLFANAKQSKTIFILQKKNEIAVEPFVYPLASLQDASVLMKFKENFQK TQG

TEIZ ID110 1902bp

ATGATTATTTTACAAGCTAATAAAATTGAACGTTCTTTTGCAGGAGAGGTTCTTTTCGATAATATCAACCTGCAGG TTGATGAACGAGATCGGATTGCTCTTGTTGGGAAAAATGGTGCAGGTAAGTCTACTCTTTTGAAGATTTTAGTTGG AGAAGAGGAGCCAACTAGCGGAGAAATCAATAAGAAAAAAGATATTTCTCTGTCTTACCTAGCCCAAGATAGCCG TTTTGAGTCTGAAAATACCATCTACGATGAAATGCTTCATGTCTΓTAATGATTTGCGTCGGACGGAGAGACAACTG CGTCAGATGGAGCTGGAGATGGGTGAAAAGTCTGGTGAGGATTTGGATAAACTGATGTCAGATTATGACCGCTTA TCTGAGAATTΓTCGCCAAGCAGGTGGCTTTACCTATGAAGCTGATATTCGAGCGATTTTGAATGGATΓCAAGTTTG ACGAGTCTATGTGGCAGATGAAAATTGCTGAGCTTTCTGGTGGTCAAAATACTCGTTTGGCACTTGCCAAAATGCT CCTTGAAAAGCCCAATCTCTTGGTCTTGGACGAGCCAACTAACCACTTGGATATTGAAACCATCGCCTGGCTAGA GAATTACTTGGTAAACTATAGCGGTGCCCTCATTATCGTCAGCCACGACCGTTATTTCTTGGACAAGGTTGCGACA

ATΓACGCTAGATTTGACCAAGCATTCCTTGGATCGCTATGTGGGGAATTACTCTCGTTTTGTCGAATTGAAGGAGC AAAAGCTAGTTACTGAGGCAAAAAACTATGAAAAGCAACAGAAGGAAATCGCTGCTCTGGAAGACTTTGTCAATC GCAATCTAGTTCGTGCTTCAACGACTAAACGTGCTCAATCTCGCCGTAAACAACTAGAAAAAATGGAGCGTTTGG ACAAGCCTGAAGCTGGCAAGAAAGCAGCCAACATGACCTTCCAGTCTGAAAAAACGTCGGGCAATGTTGTTTTGA CTGTTGAAAATGCAGCTGTTGGCTATGACGGGGAAGTCTTGTCACAACCTATCAACCTAGATCTTCGTAAGATGAA

TGCTGTCGCTATCGTTGGTCCAAATGGTATCGGCAAGTCAACCTTTATCAAGTCTATTGTGGACCAGATTCCTTTT ATCAAGGGAGAAAAGCGCTTTGGCGCTAATGTTGAGGTTGGTTACTATGACCAAACCCAAAGCAAGCTGACACCA AGTAATACGGTGCTGGATGAACTCTGGAATGATTTCAAACTGACACCAGAAGTTGAAATCCGCAACCGTCTTGGA GCCTTCCI TTCTCAGGAGATGATGTTAAAAAATCAGTCGGCATGCTATCTGGTGGCGAAAAAGCTCGTTTGCTTT TAGCTAAATTGTCTATGGAAAACAATAACTTTTTGATTCTGGATGAGCCGACCAACCACTTGGATATTGATAGTAA

GGAAGTGCTAGAAAATGCCTTGATTGACTTTGATGGAACCTTGCTGTTTGTCAGTCATGATCGTTACTTTATCAAT CGTGTGGCAACTCATGTTTTGGAATTGTCTGAGAATGGTTCAACTCTCTACCTTGGAGATTACGACTACTATGTTG AGAAGAAAGCAACAGCAGAAATGAGTCAGACTGAGGAAGCTTCAACTAGCAATCAAGCAAAGGAAGCAAGTCCA GTCAATGACTATCAGGCCCAGAAAGAAAGTCAAAAAGAAGTTCGCAAACTCATGCGACAAATCGAAAGTCTAGA AGCTGAAATTGAAGAGCTAGAAAGTCAAAGCCAAGCCATTTCTGAACAAATGTTGGAAACAAACGATGCCGACA AACTCATGGAATTACAGGCTGAGCTGGACAAAATCAGCCATCGTCAGGAAGAAGCTATGCTTGAGTGGGAAGAAT TATCAGAGCAGGTGTAA

MIILQANKIERSFAGEVLFDNINLQVDERDRIALVGKNGAG STLLKILVGEEEPTSGEINKKKDISLSYLAQDSRFESENT IYDEMLHVFNDLRRTERQLRQMELEMGEKSGEDLDKLMSDYDRLSENFRQAGGFTYEADIRAILNGFKFDESMWQMK

IAELSGGQNTRLALAKMLLEKPNLLVLDEPTNHLDIETIAWLENYLVNYSGALIIVSHDRYFLDKVATITLDLTKHSLDR YVGNYSRFVELKEQKLVTEA NYEKQQKEIAALEDFVNRNLVRASTTKRAQSRRKQLEKMERLDKPEAGKKAANMTF QSEKTSGNVVLTVENAAVGYDGEVLSQPINLDLRKMNAVAIVGPNGIGKSTFIKSIVDQIPFIKGEKRFGANVEVGYYDQ TQSKLTPSNTVLDELWNDF LTPEVEIRNRLGAFLFSGDDVKKSVGMLSGGE ARLLLAKLSMENNNFLILDEPTNHL DIDSKEVLENALIDFDGTLLFVSHDRYFINRVATHVLELSENGSTLYLGDYDYYVEKKATAEMSQTEEASTSNQA EAS

PVNDYQAQKESQKEVRKLMRQIESLEAEIEELESQSQAISEQMLETNDADKLMELQAELDKISHRQEEAMLEWEELSEQ

VZ

ID111 1179bp

ATGAATCGCTATGCAGTGCAGTTGATTAGCCGTGGGGCTATCAATAAAATGGGAAATATGCTCTATGATTATGGA AATAGTGTCTGGTTGGCTTCTATGGGGACTATAGGACAGACAGTTTTAGGAATGTATCAGATTTCTGAGCTCGTCA CATCTATTCTCGTCAATCCCTTTGGCGGAGTTATTTCAGACCGTTTTTCTCGTCGTAAGATTTTAATGACGGCAGAT CTTGTTTGTGGGATTCTTTGTCTGGCTATTTCTTTCATAAGGAATGATAGCTGGATGATTGGCGCTRRGATTGTTGC TAACATTGTGCAGGCTATTGCTTTTGCCTTTTCTCGCACAGCCAATAAAGCTATCATAACTGAAGTGGTGGAGAAA

GATGAGATTGTGATCTATAATTCTCGCTTAGAGCTGGTTTTGCAGGTTGTAGGTGTTAGCTCTCCTGTTCTTTCCTT CCTTGT TTACAGTTTGCAAGTCTCCATATGACGCTACTGCTAGACTCGCTGACTTTTTTCATΓGCTTTTGTTCTAG TGGCTΓΓCCTTCCAAAAGAGGAAGCAAAAGTTCAAGAGAAAAAGGC ΓTTACTGGGAGAGATATTTTTGTAGATA TCAAGGATGGGTTACACTATATCTGGCATCAGCAAGAAATTΓΓCTTCCTTTTGCTGGTAGCI CCAGCGTTAATTT CTTTTTTGCAGCTTTTGAATTTCTACTTCCCTTTTCGAATCAGCTTTACGGGTCAGAAGGAGCCTATGCAAGTATTT

TAACTATGGGGGCTATTGGTTCCATCATTGGGGCTCTTCTAGCTAGTAAAATTAAAGCTAATATTTATAATCTTTT GATTTTACTGGCTTTGACAGGTGTCGGAGTTTTTATGATGGGATTACCACTTCCAACTTTTCTTTCCTTTTCTGGAA ATTTAGTTTGTGAATTGTTTATGACGATTTTTAATATTCACTTTTTTACTCAAGTACAAACCAAGGTTGAGAGCGAA TTTCTTGGAAGAGTACTGAGTACAATTTTTACCTTAGCTATTCTATTTATGCCTATTGCAAAAGGATTTATGACAGT CTTGCCAAGTGTCCATCTTTATTCTTTCTTGATTATTGGACTTGGAGTTGTAGCCTTATATTTCTTAGCTCTCGGAT

ATGTTCGAACTCATTTTGAAAAATTGATATAA

MNRYAVQLISRGAINKMGNMLYDYGNSVWLASMGTIGQTVLGMYQISELVTSI VNPFGGVISDRFSRRKILMTADLV CGILCLAISFIRNDSWMIGALIVANIVQAIAFAFSRTANKAIITEVVEKDEIVIYNSRLELVLQVVGVSSPVLSFLVLQFASL HMTLLLDSLTFFIAFVLVAFLPKEEAKVQEKKAFTGRDIFVDIKDGLHYIWHQQEIFFLLLVASSVNFFFAAFEF LPFSN

SUBSTΓΓUTE SHEET (RULE 26) QLYGSEGAYASILTMGAIGSIIGALLASKIKANIYNLLILLALTGVGVFMMGLPLPTFLSFSGNLVCELFMTIFNIHFFTQV QTKVESEFLGRVLSTIFTLAILFMPIAKGFMTVLPSVHLYSF IIGLGVVALYFLALGYVRTHFE LIZ

ID113 2466bp

ATGCAAAATCAATTAAATGAATTAAAACGAAAAATGCTGGAATTTTTCCAGCAAAAACAAAAAAATAAAAAATCA GCTAGACCTGGCAAGAAAGGTTCAAGTACCAAAAAATCTAAAACCTTAGATAAGTCAGCCATTTTCCCAGCTATT TTACTGAGTATAAAAGCCTTATTTAACTTACTCTTTGTACTCGGTTTTCTAGGAGGAATGTTGGGAGCTGGGATTG CTTTGGGATACGGAGTGGCCTTATTTGACAAGGTTCGGGTGCCTCAGACAGAAGAATTGGTGAATCAGGTCAAGG ACATCTCTTCTATTTCAGAGATTACCTATTCGGACGGGACGGTGATTGCTTCCATAGAGAGTGATTTGTTGCGCAC

TTCTATCTCATCTGAGCAAATTTCGGAAAATCTGAAGAAGGCTATCATTGCGACAGAAGATGAACACTTTAAAGA ACATAAGGGTGTAGTACCCAAGGCGGTGATTCGTGCGACCTTGGGGAAATTTGTAGGTTTGGGTTCCTCTAGTGGG GGTTCAACCTTGACCCAGCAACTAATTAAACAGCAGGTGGTTGGGGATGCGCCGACCTTGGCTCGTAAGGCGGCA GAGATTGTGGATGCTCTTGCCTTGGAACGCGCCATGAATAAAGATGAGATTTTAACGACCTATCTCAATGTGGCTC CCTTTGGCCGAAATAATAAGGGACAGAATATTGCAGGGGCTCGGCAAGCAGCTGAGGGAATTTTCGGTGTAGATG

CCAGTCAGTTGACTGTTCCTCAAGCAGCATTTTTAGCAGGACTTCCACAGAGTCCCATTACTTACTCTCCTTATGA AAATACTGGGGAGTTGAAGAGTGATGAAGACCTAGAAATTGGCTTAAGACGGGCTAAGGCAGTTCTTTACAGTAT GTATCGTACAGGTGCATTAAGCAAAGACGAGTATTCTCAGTACAAGGATTATGACCTTAAACAGGACITTTTACC ATCGGGCACGGTTACAGGAATTTCACGAGACTATTTATACTTTACAACTTTGGCAGAAGCTCAAGAACGTATGTAT GACTATCTAGCTCAGAGAGACAATGTCTCCGCTAAGGAGTTGAAAAATGAGGCAACTCAGAAGTTTTATCGAGAT

TTGGCAGCCAAGGAAATTGAAAATGGTGGTTATAAGATTACTACTACCATAGATCAGAAAATTCATTCTGCCATG CAAAGTGCGGTTGCTGATTATGGCTATCTTTTAGACGATGGAACAGGTCGTGTAGAAGTAGGGAATGTCTTGATG GATAACCAAACAGGTGCTATTCTAGGCTTTGTAGGTGGTCGTAATTATCAAGAAAATCAAAATAATCATGCCTTTG ATACCAAACGTTCGCCAGCTTCTACTACCAAGCCCTTGCTGGCCTACGGTATTGCTATTGACCAGGGCTTGATGGG AAGTGAAACGATTCTATCTAACTATCCAACAAACTTTGCTAATGGCAATCCGATTATGTATGCTAATAGCAAGGG

AACAGGAATGATGACCTTGGGAGAAGCTCTGAACTATTCATGGAATATCCCTGCTTACTGGACCTATCGTATGCTC CGTGAAAAGGGTGTTGATGTCAAGGGTTATATGGAAAAGATGGGTTACGAGATTCCTGAGTACGGTATTGAGAGC TTGCCAATGGGTGGTGGTATTGAAGTCACAGTTGCCCAGCATACCAATGGCTATCAGACCTTAGCTAATAATGGA GTTTATCATCAGAAGCATGTGATTTCAAAGATTGAAGCAGCAGATGGTAGAGTGGTGTATGAGTATCAGGATAAA CCGGTTCAAGTCTATTCAAAAGCTACTGCGACGATTATGCAGGGATTGCTACGAGAAGTTCTATCCTCTCGTGTGA

CAACAACCTTCAAGTCTAACCTGACTTCTTTAAATCCTACTCTGGCTAATGCAGATTGGATTGGGAAGACTGGTAC AACCAACCAAGACGAAAATATGTGGCTCATGCTTTCGACACCTAGATTAACCCTAGGTGGCTGGATTGGGCATGA TGATAATCATTCATTGTCACGTAGAGCAGGTTATTCTAATAACTCTAATTACATGGCTCATCTGGTAAATGCGATT CAGCAAGCTTCCCCAAGCATTTGGGGGAACGAGCGCTTTGCTTTAGATCCTAGTGTAGTGAAATCGGAAGTCTTG AAATCAACAGGTCAAAAACCAGAGAAGGTTTCTGTTGAAGGAAAAGAAGTAGAGGTCACAGGTTCGACTGTTACC

AGCTATTGGGCTAATAAGTCAGGAGCGCCAGCGACAAGTTATCGCTTTGCTATTGGCGGAAGTGATGCGGATTAT CAGAATGCTTGGTCTAGTATTGTGGGGAGTCTACCAACTCCATCCAGCTCCAGCAGTTCAAGTAGTAGTTCTAGCG ATAGCAGTAACTCAAGTACTACACGACCTTCTTCTTCAAGGGCGAGACGATAA MQNQLNELKRKMLEFFQQKQKNKKSARPGKKGSSTK SKTLDKSAIFPAILLSIKALFNLLFVLGFLGGMLGAGIALGY

GVALFDKVRVPQTEELVNQVKDISSISEITYSDGTVIASIESDLLRTSISSEQISENLKKAIIATEDEHFKEHKGVVPKAVIR ATLGKFVGLGSSSGGSTLTQQLIKQQVVGDAPTLARKAAEIVDALALERAMNKDEILTTYLNVAPFGRNNKGQNIAGA RQAAEGIFGVDASQLTVPQAAF AGLPQSPITYSPYENTGELKSDEDLEIGLRRAKAVLYSMYRTGALSKDEYSQYKDY DLKQDFLPSGTVTGISRDYLYFTTLAEAQERMYDYLAQRDNVSAKELKNEATQKFYRDLAAKEIENGGYKITTTIDQKI HSAMQSAVADYGYLLDDGTGRVEVGNVLMDNQTGAILGFVGGRNYQENQNNHAFDTKRSPASTTKPLLAYGIAIDQG

LMGSETILSNYPTNFANGNPIMYANSKGTGMMTLGEALNYSWNIPAYWTYRMLREKGVDVKGYMEKMGYEIPEYGIE SLPMGGGIEVTVAQHTNGYQTLANNGVYHQKHVISKIEAADGRVVYEYQDKPVQVYSKATATIMQGLLREVLSSRVTT TFKSNLTSLNPTLANADWIGKTGTTNQDENMWLMLSTPRLTLGGWIGHDDNHSLSRRAGYSNNSNYMAHLVNAIQQA SPSI GNERFA DPSVVKSEVLKSTGQKPEKVSVEGKEVEVTGSTVTSYWANKSGAPATSYRFAIGGSDADYQNAWSSI VGSLPTPSSSSSSSSSSSDSSNSSTTRPSSSRARRZ

ID114 1974bp

ATGAAAAAATTTTATGTAAGTCCAATTTTTCCTATTCTAGTAGGATTGATTGCGTTTGGAGTCTTATCCACTTTCAT

ACTGAGAGTGCATTATACAAGGAGTGATGTAGAACAGATACAGTATGTAAACCACCAAGCGGAAGAAAGTTTGAC AGCTCTATTGGAACAGATGCCTGTAGGTGTTATGAAATTGAATTTATCTTCTGGAGAGGTTGAGTGGTTTAATCCC TATGCTGAATTGATTTTGACCAAGGAAGATGGTGATTTTGATTTAGAAGCTGTTCAAACGATTATCAAGGCTTCAG TAGGAAATCCGTCTACTTATGCCAAGCTTGGTGAGAAGCGTTATGCTGTTCATATGGATGCTTCTTCCGGTGTTTT GTATTTTGTAGATGTATCCAGGGAACAAGCCATAACAGATGAATTGGTAACAAGTAGACCAGTGATTGGGATTGT

CTCTGTGGATAATTATGATGATTTGGAGGATGAAACTTCTGAGTCAGATATTAGTCAAATCAATAGTTTTGTAGCT AATTTTATATCAGAGTTTTCAGAAAAACACATGATGTTTTCTCGTCGGGTAAGTATGGATCGATTTTATCTATTTAC TGACTACACGGTGCTTGAGGGCTTGATGAATGATAAATTTTCTGTTATTGATGCTTTCAGAGAAGAGTCGAAACAG AGACAGTTGCCCTTGACCTTAAGTATGGGATTTTCTTATGGCGATGGAAATCATGATGAGATAGGGAAAGTTGCTT TGCTCAATTTGAACTTGGCTGAAGTACGTGGTGGCGACCAGGTGGTTGTTAAGGAAAACGACGAAACGAAAAATC CAGTTTATTTTGGTGGTGGGTCTGCTGCTTCAATCAAGCGTACACGGACTCGTACGCGCGCTATGATGACAGCTAT TTCAGATAAGATTCGGAGTGTAGATCAGGTTTTTGTAGTCGGTCACAAAAATTTAGACATGGATGCTTTGGGCTCT GCTGTAGGTATGCAGTTGTTCGCCAGCAATGTGATTGAAAATAGCTATGCTCTTTATGATGAAGAACAAATGTCTC CAGATATTGAACGAGCTGTTTCATTCATAGAAAAAGAAGGAGTTACGAAGTTGTTGTCTGTTAAGGATGCAATGG GGATGGTGACCAATCGTTCTTTGTTGATTCTTGTAGACCATTCAAAGACAGCCTTAACATTATCAAAAGAATTTTA

TGATTTATTTACCCAAACCATTGTTATTGACCACCATAGAAGGGATCAGGATTTTCCAGATAATGCGGTTATTACT TATATCGAAAGTGGTGCAAGTAGTGCCAGTGAGTTGGTAACGGAATTGATTCAGTTCCAGAATTCTAAGAAAAAT CGTTTGAGTCGTATGCAAGCAAGTGTCTTGATGGCTGGTATGATGTTGGATACTAAAAATTTCACCTCGCGAGTAA CTAGTCGGACATTTGATGTTGCTAGCTATCTCAGAACGCGCGGAAGTGATAGTATTGCTATCCAGGAAATCGCTGC GACAGATTTTGAAGAATATCGTGAGGTCAATGAACTTATTTTACAGGGGCGTAAATTAGGTTCAGATGTACTAATA

GCAGAGGCTAAGGACATGAAATGCTATGATACAGTTGTTATTAGTAAGGCAGCAGATGCCATGTTAGCCATGTCA GGTATTGAAGCGAGTTTTGTTCTTGCGAAGAATACACAAGGATTTATCTCTATCTCAGCTCGAAGTCGTAGTAAAC TGAATGTACAACGGATTATGGAAGAGTTAGGCGGTGGAGGCCACTTTAATTTGGCAGCAGCTCAAATTAAAGATG TAACCTTGTCAGAAGCAGGTGAAAAACTGACAGAAATTGTATTAAATGAAATGAAGGAAAAGGAGAAAGAAGAA TGA

MKKFYVSPIFPILVGLIAFGVLSTFIIFVNNNLLTVLILFLFVGGYVFLFKKLRVHYTRSDVEQIQYVNHQAEESLTALLE

QMPVGVMKLNLSSGEVEWFNPYAELILTKEDGDFDLEAVQTIIKASVGNPSTYAKLGEKRYAVHMDASSGVLYFVDVS

REQAITDELVTSRPVIGIVSVDNYDDLEDETSESDISQINSFVANFISEFSEKHMMFSRRVSMDRFYLFTDYTVLEGLMN DKFSVIDAFREESKQRQLPLTLSMGFSYGDGNHDEIGKVALLNLNLAEVRGGDQVVVKENDETKNPVYFGGGSAASIK

RTRTRTRAMMTAISDKIRSVDQVFVVGHKNLDMDALGSAVGMQLFASNVIENSYALYDEEQMSPDIERAVSFIEKEGV T LLSVKDAMGMVTNRSLLILVDHSKTA TLSKEFYDLFTQTIVIDHHRRDQDFPDNAVITYIESGASSASELVTELIQFQ NSKKNRLSRMQASVLMAGMMLDTKNFTSRVTSRTFDVASYLRTRGSDSIAIQEIAATDFEEYREVNELILQGRKLGSDV LIAEAKDMKCYDTVVISKAADAMLAMSGIEASFVLAKNTQGFISISARSRSKLNVQRIMEELGGGGHFNLAAAQIKDVT LSEAGEK TEIVLNEMKEKEKEEZ

ID115 663bp

ATGAAGTGCTTGTTATGTGGGCAGACTATGAAGACTGTTTTAACTTTTAGTAGTCTCTTACTTCTGAGGAATGATG ACRCTTGTCTTTGTTCAGACTGTGATTCTACTTTTGAAAGAATTGGGGAAGAGAACTGTCCAAATTGTATGAAAAC

AGAGTTGTCAACAAAGTGTCAAGATTGTCAACTTTGGTGTAAAGAGGGAGTTGAAGTCAGTCATAGAGCGATTTT TACTTACAATCAAGCTATGAAGGATTTTTTCAGTCGGTATAAGTTTGATGGAGACTTCCTGTTAAGAAAAGTTTTC GCTΓCATTTTTAAGTGAGGAGTTGAAAAAGTACAAAGAGTATCAATTTGTTGTAATTCCCCTAAGTCCTGATAGAT ATGC AATAGAGGATTTAATCAGGTTGAGGGCTTGGTAGAGGCAGCAGGCITTGAGTATCTGGATTTATTAGAGA AAAGAGAAGAGAGAGCCAGTTCTTCTAAAAATCGTTCAGAGCGCTTGGGGACAGAACTTCCRRTCTTTATTAAAA

GTGGAGTCACTATTCCTAAAAAAATCCTACTTATAGATGATATCTATACTACAGGAGCAACTATAAATCGTGTTAA GAAACTGTTGGAAGAAGCTGGTGCTAAGGATGTAAAAACATTTTCCCTTGTAAGATGA

M CLLCGQTMKTVLTFSSLLLLRNDDSCLCSDCDSTFERIGEENCPNCMKTELSTKCQDCQLWCKEGVEVSHRAIFTY NQAMKDFFSRYKFDGDFLLRKVFASFLSEELKKYKEYQFVVIPLSPDRYANRGFNQVEGLVEAAGFEYLD LEKREER

ASSSKNRSERLGTELPFFIKSGVTIPKKILLIDDIYTTGATINRVKKLLEEAGAKDVKTFSLVRZ

ID116 1299bp ATGAAAGTAAATTTAGATTATCTCGGTCGTTTATTTACTGAGAATGAATTAACAGAAGAAGAACGTCAGTTGGCG

GAGAAACI CCAGCAATGAGAAAGGAGAAGGGGAAACTTTTCTGTCAACGCTGTAATAGTACTATTCTAGAAGAA TGGTATTTGCCCATCGGTGCTTACTATTGTCGAGAGTGCTTGCTGATGAAGCGAGTCAGAAGTGATCAAACTTTAT ACTATTTTCCGCAGGAGGATTTTCCAAAGCAAGATGTTCTCAAATGGCGCGGCCAATTAACTCCTTTTCAAGAGAA GGTGTCAGAGGGATTGCTTCAAGTAGTAGACAAGCAAAAGCCAACCTTAGTTCATGCGGTAACAGGAGCTGGAAA GACAGAAATGATTTATCAAGTAGTGGCTAAAGTGATCAATGCGGGTGGTGCAGTGTGTTTGGCTAGTCCTCGCAT

AGATGTTTGTTTGGAGCTGTACAAGCGCCTGCAACAGGATTTTTCTTGCGGGATAGCTTTGCTACATGGAGAATCG GAACCTTATTTTCGAACACCACTAGTΓGTTGCAACAACCCATCAGTTATTGAAGTTTTATCAAGCTTTΓGATTTGCT GATAGTGGATGAAGTAGATGCTTITCCTTATGTTGATAATCCCATGCTTTACCACGCTGTCAAGAATAGTGTAAAG AAAAGACTGAATTTACCGAGACGGTTTCATGGAAATCCGTTGATTATTCCAAAACCAAT TGGTTATCGGATTTTA

ATCGCTACTTAGACAAGAATCGTTTGTCACCAAAGTTAAAGTCCTATATTGAGAAGCAGAGAAAGACAGCTTATC CGTTACTCATTTTTGCTTCAGAAATTAAGAAAGGGGAGCAGTTAGCAGAAATCTTACAGGAGCAATTTCCAAATG AGAAAATTGGCTTTGTATCTTCTGTAACAGAGGATCGATTAGAGCAAGTACAAGCTTTTCGAGATGGAGAACTGA CAATACTTATCAGTACGACAATCTTGGAGCGCGGAGTTACCTTCCCTΓGTGTGGATGTTTTCGTAGTAGAGGCCAA TCATCGTTTGTTTACCAAGTCTAGTTTGATTCAGATTGGTGGACGAGTTGGACGAAGCATGGATAGACCGACAGGA

GATTTGCTTTTCTTCCATGATGGGTTAAATGCTTCAATCAAGAAGGCGATTAAGGAAATTCAGATGATGAATAAGG AGGCTGGTCTATGA

MKVNLDYLGRLFTENELTEEERQLAEKLPAMRKEKGKLFCQRCNSTILEEWYLPIGAYYCRECLLMKRVRSDQTLYYF PQEDFPKQDVLKWRGQLTPFQEKVSEGLLQVVDKQKPTLVHAVTGAGKTEMIYQVVAKVINAGGAVCLASPRIDVCL ELYKRLQQDFSCGIALLHGESEPYFRTPLVVATTHQ LKFYQAFDLLIVDEVDAFPYVDNPMLYHAV NSVKENGLRIF LTATSTNELD KVRLGELKRLNLPRRFHGNPLIIPKPIWLSDFNRYLDKNRLSPKLKSYIEKQRKTAYPLLIFASEIKKGE QLAEILQEQFPNEKIGFVSSVTEDRLEQVQAFRDGELTILISTTILERGVTFPCVDVFVVEANHRLFT SSLIQIGGRVGRS MDRPTGDLLFFHDGLNASI KAIKEIQMMNKEAGLZ

ID117 870bp

ATGCAAATTCAAAAAAGTTTTAAGGGGCAGTCTCCCTATGGCAAGCTGTATCTAGTGGCAACGCCGATTGGCAAT CTAGATGATATGACTTTTCGTGCTATCCAGACCTTGAAAGAAGTGGACTGGATTGCTGCTGAGGATACGCGCAAT ACAGGGCTTTTGCTCAAGCATTTΓGACATTTCCACCAAGCAGATCAGTTTTCATGAGCACAATGCCAAGGAAAAA

ATTCCTGATTTGATTGGTTTCTTGAAAGCAGGGCAAAGTATTGCTCAGGTCTCTGATGCCGGTTTGCCTAGCATTT CAGACCCTGGTCATGATTTAGTTAAGGCAGCTATTGAGGAAGAAATTGCAGTTGTGACAGTTCCAGGTGCCTCTGC AGGAATTTCTGCCTTGATTGCCAGTGGTTTAGCGCCACAGCCACATATCTTTTACGGTTTTTTACCGAGAAAATCA GGTCAGCAGAAGCAATTTTTTGGCTTGAAAAAAGATTATCCTGAAACACAGATTTTTTATGAATCACCTCATCGTG TAGCAGACACGTTGGAAAATATGTTAGAAGTCTACGGTGACCGCTCCGTTGTCTTGGTCAGGGAATTGACCAAAA

TCTATGAAGAATACCAACGAGGTACTATCTCTGAGTTATTAGAAAGCATTGCTGAAACGCCACTCAAGGGCGAAT GTCTTCTCATTGTTGAGGGTGCCAGTCAGGGTGTGGAGGAAAAGGACGAGGAAGACTTGTTCGTAGAAATTCAAA CCCGCATCCAGCAAGGTGTGAAGAAAAACCAAGCTATCAAGGAAGTCGCTAAGATTTACCAGTGGAATAAAAGTC AGCTCTACGCTGCCTACCACGACTGGGAAGAAAAACAATAA

MQIQKSFKGQSPYGKLYLVATPIGNLDDMTFRAIQTLKEVDWIAAEDTRNTGLLLKHFDISTKQISFHEHNAKEKIPDLI GFLKAGQSIAQVSDAGLPSISDPGHDLVKAAIEEEIAVVTVPGASAGISALIASGLAPQPHIFYGFLPRKSGQQKQFFGLKK DYPETQIFYESPHRVADTLENMLEVYGDRSVVLVRELTKIYEEYQRGTISELLESIAETPLKGECLLIVEGASQGVEEKDE EDLFVEIQTRIQQGVKKNQAIKEVAKIYQ NKSQLYAAYHDWEEKQZ

ID118 345bp

ATGATAAAGAAAGGAAAGGGCTGTTTTATGGACAAAAAAGAATTATTTGACGCGCTGGATGATTTTTCCCAACAA TTATTGGTAACCTTAGCCGATGTGGAAGCCATCAAGAAAAATCTCAAGAGCCTGGTAGAGGAAAATACAGCTCTT CGCTTGGAAAATAGTAAGTTGCGAGAACGCTTGGGTGAGGTGGAAGCAGATGCTCCTGTCAAGGCCAAGCATGTT

CGCGAAAGTGTCCGTCGTATTTACCGTGATGGATTTCACGTATGTAATGATTTTTATGGACAACGTCGAGAGCAGG ACGAAGAATGTATGTTTTGTGACGAGTTGTTATACAGGGAGTAA

MIKKGKGCFMDKKELFDALDDFSQQLLVTLADVEAIKKNLKSLVEENTALRLENSKLRER GEVEADAPVKAKHVRES VRRIYRDGFHVCNDFYGQRREQDEECMFCDELLYREZ

ID119 639bp

ATGTCAAAAGGATTTTTAGTCTCTCTTGAGGGACCAGAGGGAGCAGGCAAGACCAGTGTTTTAGAGGCTCTGCTA CCAATTTTAGAGGAAAAAGGAGTAGAGGTGTTGACGACCCGTGAACCTGGCGGAGTCTTGATTGGGGAGAAGATT

CGGGAAGTGATTTTGGATCCAAGTCATACTCAGATGGATGCTAAAACAGAGCTACTTCTCTATATTGCCAGTCGCA GACAGCATTTGGTGGAAAAAGTTCTTCCAGCCCTTGAAGCTGGCAAGTTGGTCATCATGGATCGTTTTATCGATAG TTCTGTTGCCTATCAGGGATTTGGTCGTGGCTTAGATATTGAAGCCATTGACTGGCTCAATCAGTTTGCGACAGAT GGCCTCAAACCCGATTTGACACTCTATTTTGACATCGAGGTGGAAGAAGGGCTGGCTCGTATTGCTGCTAATAGTG ACCGCGAGGTTAATCGTTTGGATTTGGAAGGGTTGGACTTGCATAAAAAAGTTCGTCAAGGCTACCTTTCTCTTCT

GGATAAAGAGGGAAATCGCATTGTCAAGATTGATGCTAGTCTCCCTTTGGAGCAAGTTGTGGAAACTACCAAGGC TGTCTTGTTTGACGGAATGGGCTTGGCCAAATGA

MSKGFLVSLEGPEGAGKTSVLEALLPILEEKGVEVLTTREPGGVLIGEKIREVILDPSHTQMDAKTELLLYIASRRQHLVE VLPALEAGKLVIMDRFIDSSVAYQGFGRGLDIEAIDWLNQFATDGLKPDLTLYFDIEVEEGLARIAANSDREVNRLDL

EGLDLHKKVRQGYLSLLDKEGNRIVKIDASLPLEQVVETTKAVLFDGMGLAKZ

ID120 408bp ATGGTAGAACAAAGAAAATCAATTACCATGAAAGATGTTGCTTTAGAAGCAGGAGTTAGTGTTGGAACTGTTTCA

CGTGTAATTAATAAAGAAAAAGGCATTAAAGAAGTAACTTTGAAAAAAGTGGAACAAGCGATTAAAACTTTGAAT TACATTCCAGATTACTACGCTAGAGGAATGAAAAAAAATCGAACAGAAACGATTGCAATCATTGTACCAAGTATC TGGCATCCCTTCTTTTCAGAATTTGCTATGCATGTGGAAAATGAAGTCTATAAGAGAAATAACAAATTACTCTTAT GTTCTATCAATGGTACAAATAGAGAGCAAGACTATCTGGAGATGTTGCGTCATAATAAAGTTGATGGAGTGGTTG CCATTACCTATAGGCCAATTGAACATTACTTGACGTCAGGAATTCCCTTTGTTAGTATTGACCGCACATACTCAGA

GATTGCCATTCCTTGTGTTrCA

MVEQRKSITM DVALEAGVSVGTVSRVINKEKGIKEVTLKKVEQAI TLNYIPDYYARGMKKNRTETIAIIVPSIWHPFF SEFAMHVENEVYKRNNK LLCSINGTNREQDYLEMLRHNKVDGVVAITYRPIEHYLTSGIPFVSIDRTYSEIAIPCVS ID121 285bp

ATGAATATATTTAGAACAAAGAATGTTAGTTTAGATAAAACAGAGATGCATAGGCATTTGAAGTTATGGGATTTG ATTTTGCTGGGTATCGGAGCCATGGTAGGGACAGGCGTCTTTACAATCACAGGTACTGCAGCTGCAACACTTGCTG

TCGCGAGTACCCGCTACAGGAGGTGCCTATAGTTACCTCTATGCTATCTTAGGAGAATTCCCTGCCTGGTTGGCTG GTTGGTTAACCATGATGGAGTTCATGACAGCCATATCAGGCGTAGCTTCGGGTTGGGCAGCTTATTTTAA

MNIFRTKNVSLDKTEMHRHLKLWDLILLGIGAMVGTGVFTITGTAAATLAGPALVISIVISALCVGLSALFFAEFASRVP ATGGA YS YLYAILGEFPAWLAGWLTMMEFMTAISGVASGWAAYF

ID124 131 lbp

ATGAAATCAAGAGTAAAGGAAACGAGTATGGATAAAATTGTGGTTCAAGGTGGCGATAATCGTCTGGTAGGAAGC GTGACGATCGAGGGAGCAAAAAATGCAGTCTTACCCTTGTTGGCAGCGACTATTCTAGCAAGTGAAGGAAAGACC

GTCTTGCAGAATGTTCCGATTTTGTCGGATGTCTTTATTATGAATCAGGTAGRRGGTGGTTTGAATGCCAAGGTTG ACTTTGATGAGGAAGCTCATCTTGTCAAGGTGGATGCTACTGGCGACATCACTGAGGAAGCCCCTTACAAGTATG TCAGCAAGATGCGCGCCTCCATCGTTGTATTAGGGCCAATCCTTGCCCGTGTGGGTCATGCCAAGGTATCCATGCC AGGTGGTTGTACGATTGGTAGCCGTCCTATTGATCTTCATTTGAAAGGTCTGGAAGCTATGGGGGTTAAGATTAGT CAGACAGCTGGTTACATCGAAGCCAAGGCAGAACGCTTGCATGGTGCTCATATCTATATGGACTTTCCAAGTGTTG

GTGCAACGCAGAACTTGATGATGGCAGCGACTCTGGCTGATGGGGTGACAGTGATTGAGAATGCTGCGCGTGAGC CTGAGATTGTTGACTTAGCCATTCTCCTTAATGAAATGGGAGCCAAGGTCAAAGGTGCTGGTACAGAGACTATAA CCATTACTGGTGTTGAGAAACTTCATGGTACGACTCACAATGTAGTCCAAGACCGTATCGAAGCAGGAACCTTTAT GGTAGCTGCTGCCATGACTGGTGGTGATGTCTTGATTCGAGACGCTGTCTGGGAGCACAACCGTCCCTTGATTGCC AAGTTACTTGAAATGGGTGTTGAAGTAATTGAAGAAGACGAAGGAATTCGTGTTCGTTCTCAACTAGAAAATCTA

AAAGCTGTTCATGTGAAAACCTTGCCCCACCCAGGATTTCCAACAGATATGCAGGCTCAATTTACAGCCTTGATGA CAGTTGCAAAAGGCGAATCAACCATGGTGGAGACAGTTTTCGAAAATCGTTTCCAAACCTAGAAGAGATGCGCCG CATGGGCTΓGCATTCTGAGATTATCCGTGATACAGCTCGTATTGTTGGTGGACAGCCTTTGCAGGGAGCAGAAGTT CTTTCAACTGACCTTCGTGCCAGTGCGGCCTTGATTTTGACAGGTTTGGTAGCACAGGGAGAAACTGTGGTCGGTA AARRGGTTCACTTGGATAGAGGTTACTACGGTTTCCATGAGAAGTTGGCGCAGCTAGGTGCTAAGATTCAGCGGAT

TGAGGCAAGTGATGAAGATGAATAA

MKSRVKETSMDKIVVQGGDNRLVGSVTIEGAKNAVLPLLAATILASEGKTVLQNVPILSDVFIMNQVVGGLNAKVDFD EEAHLVKVDATGDITEEAPYKYVS MRASIVVLGPILARVGHAKVSMPGGCTIGSRPIDLHLKGLEAMGVKISQTAGYIE AKAERLHGAHIYMDFPSVGATQNLMMAATLADGVTVIENAAREPEIVDLAILLNEMGAKVKGAGTETITITGVEKLHG

TTHNVVQDRIEAGTFMVAAAMTGGDVLIRDAVWEHNRPLIA LLEMGVEVIEEDEGIRVRSQLENLKAVHVKTLPHP GFPTDMQAQFTALMTVAKGESTMVETVFENRFQHLEEMRRMGLHSEIIRDTARIVGGQPLQGAEVLSTDLRASAALIL TGLVAQGETVVGKLVHLDRGYYGFHEKLAQLGAKIQRIEASDEDEZ ID125 HOlbp

ATGTTATTAGCGTCAACAGTAGCCTTGTCATTTGCCCCAGTATTGGCAACTCAAGCAGAAGAAGTTCTTTGGACTG CACGTAGTGTTGAGCAAATCCAAAACGATTTGACTAAAACGGACAACAAAACAAGTTATACCGTACAGTATGGTG ATACTTTGAGCACCATTGCAGAAGCCTTGGGTGTAGATGTCACAGTGCTTGCGAATCTGAACAAAATCACTAATAT GGACTTGATTTTCCCAGAAACTGTTTTGACAACGACTGTCAATGAAGCAGAAGAAGTAACAGAAGTTGAAATCCA

AACACCTCAAGCAGACTCTAGTGAAGAAGTGACAACTGCGACAGCAGATTTGACCACTAATCAAGTGACCGTTGA TGATCAAACTGTTCAGGTTGCAGACCTTTCTCAACCAATTGCAGAAGTTACAAAGACAGTGATTGCTTCTGAAGAA GTGGCACCATCTACGGGCACTTCTGTCCCAGAGGAGCAAACGACCGAAACAACTCGCCCAGTTGCAGAAGAAGCT CCTCAGGAAACGACTCCAGCTGAGAAGCAGGAAACACAAACAAGCCCTCAAGCTGCATCAGCAGTGGAAGCAAC TACAACAAGTTCAGAAGCAAAAGAAGTAGCATCATCAAATGGAGCTACAGCAGCAGTTTCTACTTATCAACCAGA

AGAAACGAAAGTAATTTCAACAACTTACGAGGCTCCAGCTGCGCCCGATTATGCTGGACTTGCAGTAGCAAAATC TGAAAATGCAGGTCTTCAACCACAAACAGCTGCCTTrAAWGAAGAAATTGCTAACTTGTTTGGCATTACATCCTTT AGTGGTTATCGTCCAGGAGACAGTGGAGATCACGGAAAAGGTTTGGCTATCGACTTTATGGTACCAGAACGTTCA GAATTAGGGGATAAGATTGCGGAATATGCTATTCAAAATATGGCCAGCCGTGGCATTAGTTACATCATCTGGAAA CAACGTTTCTATGCTCCATTCGATAGCAAATATGGGCCAGCTAACACTTGGAACCCAATGCCAGACCGTGGTAGT

GTGACAGAAAATCACTATGATCACGTTCACGTTTCAATGAATGGATAA

MLLASTVALSFAPVLATQAEEVLWTARSVEQIQNDLTKTDNKTSYTVQYGDTLSTIAEALGVDVTVLANLNKITNMDL IFPETVLTTTVNEAEEVTEVEIQTPQADSSEEVTTATADLTTNQVTVDDQTVQVADLSQPIAEVTKTVIASEEVAPSTGTS VPEEQTTETTRPVAEEAPQETTPAEKQETQTSPQAASAVEATTTSSEAKEVASSNGATAAVSTYQPEETKVISTTYEAPA

APDYAGLAVAKSENAGLQPQTAAFKKKLLTC ALHPLVVIVQETVEITEKVWLSTLWYQNVQNZGIRLRNMLFKIWPA VALVTSSGNNVSMLHSIANMGQLTLGTQCQTVVVZQKITMITFTFQZMD ID126 1281bp TTGTTTAAGAAAAATAAAGACATTCTTAATATTGCATTGCCAGCTATGGGTGAAAACTTTTTGCAGATGCTAATGG

GAATGGTGGACAGRRATTTGGTTGCTCATTTAGGATTGATAGCTATTTCAGGGGTTTCAGTAGCTGGTAATATTAT CACCATTΓATCAGGCGATTTTCATCGCTCTGGGAGCTGCTATTTCCAGTGTTATTTCAAAAAGCATAGGGCAGAAA GACCAGTCGAAGTTGGCCTATCATGTGACTGAGGCGTTGAAGATTACCTTACTATTAAGTTTCCITTTAGGATTTT TGTCCATCTTCGCTGGGAAAGAGATGATAGGACTTTTGGGGACGGAGAGGGATGTAGCTGAGAGTGGTGGACTGT ATCTATCTTTGGTAGGCGGATCGATTGTTCTCTTAGGTTTAATGACTAGTCTAGGAGCCTTGATTCGTGCAACGCA TAATCCACGTCTGCCTCTCTATGTTAGTTTTTTATCCAATGCCTTGAATATTCTTTTTTCAAGTCTAGCTATTTTTGT TCTGGATATGGGGATAGCTGGTGTTGCTTGGGGGACAATTGTGTCTCGTTTGGTTGGTCTTGTGATTTTGTGGTCAC AATTAAAACTGCCTTATGGGAAGCCAACTTTTGGTTTAGATAAGGAACTGTTGACCTTGGCTTTACCAGCAGCTGG AGAGCGACTTATGATGAGGGCTGGAGATGTAGTGATCATTGCCTTGGTCGTTTCTTTTGGGACGGAGGCAGTTGCT GGGAATGCAATCGGAGAAGTCTTGACCCAGTTTAACTATATGCCTGCCTTTGGCGTCGCTACGGCAACGGTCATG

CTGTTGGCCCGAGCAGTTGGAGAGGATGATTGGAAAAGAGTTGCTAGTTTGAGTAAACAAACCTΠTGGCTTTCTC TGTTCCTCATGTTGCCCCTGTCCTTTAGTATATATGTCTTGGGTGTACCATTAACTCATCTCTATACGACTGATTCT CTAGCGGTGGAGGCTAGTGTTCTAGTGACACTGTTTTCACTACTTGGGACCCCTATGACGACAGGAACAGTCATCT ATACGGCAGTCTGGCAGGGATTAGGAAATGCACGCCTCCCTTTTTATGCGACAAGTATAGGAATGTGGTGTATCC GCATTGGGACAGGATATCTGATGGGGATTGTGCTTGGTTGGGGCTTGCCTGGTATTTGGGCAGGGTCTCTCTTGGA TAATGGTTTTCGCTGGTTATTTCTACGCTATCGTTACCAGCGCTATATGAGCTTGAAAGGATAG

LFKKNKDILNIALPAMGENFLQMLMGMVDSYLVAHLGLIAISGVSVAGNIITIYQAIFIALGAAISSVIS SIGQKDQSKLA YHVTEALKITLLLSFLLGFLSIFAGKEMIGLLGTERDVAESGGLYLSLVGGSIVLLGLMTSLGALIRATHNPRLPLYVSFL SNALNILFSSLAIFVLDMGIAGVAWGTIVSRLVGLVILWSQLKLPYGKPTFGLD ELLTLALPAAGERLMMRAGDVVΠA

LVVSFGTEAVAGNAIGEVLTQFNYMPAFGVATATVMLLARAVGEDDWKRVASLSKQTFWLSLFLMLPLSFSIYVLGVP LTHLYTTDSLAVEASVLVTLFSLLGTPMTTGTVIYTAVWQGLGNARLPFYATSIGMWCIRIGTGYLMGIVLGWGLPGIW AGSLLDNGFRWLFLRYRYQRYMSLKGZ ID127 894bp

GTGGGAAGAATTATCAGAGCAGGTGTAAAGATGGAACATCTTGGAAAAGTATTTCGTGAATTTCGAACAAGTGGA AAT ATTCTTTAAAGGAAGCAGCAGGCGAATCCTGCTCTACCTCTCAGTTATCTCGCTTTGAGCTTGGGGAGTCTG ACCTGGCAGTCTCCCGTTTCT TGAGATTTTGGATAACATTCATGTAACAATCGAAAATTTCATGGATAAGGCAAG GAATTTTCATAATCATGAACATGTGTCTATGATGGCACAGATTATCCCACTTTACTATTCAAACGATATTGCAGGT

TTTCAAAAGCTTCAAAGAGAACAACTTGAAAAGTCTAAGAGTTCGACGACTCCCCTTTATTTTGAGCTGAACTGGA TTTTGCTACAAGGTCTGATTTGTCAAAGAGATGCGAGTTATGATATGAAGCAGGATGATTTGGGTAAGGTAGCAG AT ATCΓCTTCAAAACAGAAGAATGGACCATGTATGAGTTGATTCTΠTCGGTAACCTCTATAGTTTCTACGATGT AGACTATGTCACTCGGATTGGTAGAGAAGTTATGGAGAGGGAGGAATTTTACCAAGAGATTAGTCGCCATAAGAG ATTAGTGTTGATTTTGGCCCTCAATTGTTACCAGCATTGTTTAGAGCATTCTTCTTΤRTATAATGCCAACTATTTTG AGGCTTATACAGAGAAGATTATTGACAAAGGTATTAAGCTTTATGAGCGTAATGTTI CCATTATTTAAAAGGTTT TGCCTTATATCAAAAAGGACAGTGTAAAGAAGGCTGTAAGCAGATGCAAGAGGCCATGCATATTTTTGATGTGTT AGGTCTTCCAGAGCAAGTAGCCTATTATCAGGAACACTACGAAAAATTTGTCAAAAGTTAA VGRIIRAGVKMEHLGKVFREFRTSGNYSLKEAAGESCSTSQLSRFELGESDLAVSRFFEILDNIHVTIENFMDKARNFHN

HEHVSMMAQΠPLYYSNDIAGFQKLQREQLEKSKSSTTPLYFELNWILLQGLICQRDASYDM QDDLGKVADYLFKTEE WTMYELILFGNLYSFYDVDYVTRIGREVMEREEFYQEISRHKRLVLILALNCYQHCLEHSSFYNANYFEAYTEKIIDKGI KLYERNVFHYLKGFALYQKGQCKEGCKQMQEAMHIFDVLGLPEQVAYYQEHYEKFVKSZ

TABLE 3

ID1 1068bp ATGTCTAACATTCAAAACATGTCCCTGGAGGACATCATGGGAGAGCGCTTTGGTCGCTACTCCAAGTACATTATTC

AAGACCGGGCTTTGCCAGATATTCGTGATGGGTTGAAGCCGGTTCAGCGCCGTATTCTTTATTCTATGAATAAGGA TAGCAATACTTTTGACAAGAGCTACCGTAAGTCGGCCAAGTCAGTCGGGAACATCATGGGGAATTTCCACCCACA CGGGGATTCTTCTATCTATGATGCCATGGTTCGTATGTCACAGAACTGGAAAAATCGTGAGATTCTAGTTGAAATG CACGGTAATAACGGTTCTATGGACGGAGATCCTCCTGCGGCTATGCGTTATACTGAGGCACGTTTGTCTGAAATTG CAGGCTACCTTCTTCAGGATATCGAGAAAAAGACAGTTCCTTTTGCATGGAACTTTGACGATACGGAGAAAGAAC

CAACGGTCTTGCCAGCAGCCTTTCCAAACCTCTTGGTCAATGGTTCGACTGGGATTTCGGCTGGTTATGCCACAGA CATTCCTCCCCATAATTTAGCTGAGGTCATAGATGCTGCAGTTTACATGATTGACCACCCAACTGCAAAGATTGAT AAACTCATGGAATTCTTGCCTGGACCAGACTTCCCTACAGGGGCTATTATTCAGGGTCGTGATGAAATCAAGAAA GCTTATGAGACTGGGAAAGGGCGCGTGGTTGTTCGTTCCAAGACTGAAATTGAAAAGCTAAAAGGTGGTAAGGAA CAAATCGTTATTATTGAGATTCCTTATGAAATCAATAAGGCCAATCTAGTCAAGAAAATCGATGATGTTCGTGTTA

ATAACAAGGTAGCTGGGATTGCTGAGGTTCGTGATGAGTCTGACCGTGATGGTCTTCGTATCGCTATCGAACTTAA GAAAGACGCTAATACTGAGCTTGTTCTCAACTACTTATTTAAGTACACCGACCTACAAATCAACTACAACTTTAAT ATGGTGGCGATTGACAATTTCACACCTCGTCAGGTTGGATTGTTCCAATCCTGTCTAGCTATATCGCTCACCGTCG AGAAGTGA

MSNIQNMSLEDIMGERFGRYSKYIIQDRALPDIRDGLKPVQRRILYSMNKDSNTFDKSYRKSAKSVGNIMGNFHPHGDS SIYDAMVRMSQNWKNREILVEMHGNNGSMDGDPPAAMRYTEARLSEIAGYLLQDIEKKTVPFAWNFDDTEKEPTV P AAFPNLLVNGSTGISAGYATDIPPHNLAEVIDAAVYMIDHPTAKIDKLMEFLPGPDFPTGAIIQGRDEIKKAYETGKGRV VVRSKTEIEKLKGGKEQIVIIEIPYEINKANLVKKIDDVRVNNKVAGIAEVRDESDRDGLRIAIELKKDANTELVLNYLFK YTDLQINYNFN VAIDNFTPRQVGLFQSCLAISLTVEKZ

ID12 684bp

ATGCCGACATTAGAAATAGCACAAAAAAAACTGGAGTTCATTAAGAAGGCAGAAGAATATTACAATGCCTTGTGT ACAAATATACAGTTGAGCGGAGATAAACTAAAAGTAATTTCCGTTACTTCTGTTAACCCTGGGGAAGGAAAAACA

ACTACTTCCATAAATATAGCATGGTCGTTTGCGCGTGCAGGCTATAAAACTCTTTTGATCGATGGCGATACTCGAA ATTCAGTTATGTTAGGAGTTTTTAAATCTCGTGAAAAAATTACAGGGCTAACAGAATTΓTTATCTGGGACAGCTGA TTTATCTCACGGTTTATGTGATACAAATATTGAAAATTTATTTGTAGTTCAATCGGGATCTGTATCACCAAACCCT ACAGCCTTGTTACAAAGTAAAAATTTTAATGATATGATTGAAACATTGCGTAAATATTTTGATTATATCATTATTG ATACACCGCCTATTGGAATTGTTATTGATGCGGCAATTATCACTCAAAAGTGTGATGCGTCCATCTTGGTAACAGC

AACAGGTGAGGCGAATAAACGTGATATCCAAAAAGCGAAACAACAATTAAAACAAACAGGGAAACTGTTCCTAG GAGTTGTTTTAAATAAATTGGATATCTCGGTTAATAAGTATGGAGTTTACGGTTCCTATGGAAATTATGGTAAAAA ATAA MPTLEIAQKKLEFIK AEEYYNALCTNIQLSGDKLKVISVTSVNPGEGKTTTSINIAWSFARAGY TLLIDGDTRNSVML

GVFKSREKITGLTEFLSGTADLSHGLCDTNIENLFVVQSGSVSPNPTALLQSKNFNDMIET RKYFDYIΠDTPPIGIVIDAA IITQKCDASILVTATGEANKRDIQKAKQQLKQTGKLFLGVVLNKLDISVNKYGVYGSYGNYGKKZ

ID13 1182bp

ATGGAGGCAAATATGAAACATCTAAAAACATTTTACAAAAAATGGTTTCAATTATTAGTCGTTATCGTCATTAGCT TTTTTAGTGGAGCCTTGGGTAGTTTTTCAATAACTCAACTAACTCAAAAAAGTAGTGTAAACAACTCTAACAACAA TAGTACTATTACACAAACTGCCTATAAGAACGAAAATTCAACAACACAGGCTGTTAACAAAGTAAAAGATGCTGT TGTT CTGTTATTACTTATTCGGCAAACAGACAAAATAGCGTATTTGGCAATGATGATACTGACACAGATTCTCAG CGAATCTCTAGTGAAGGATCTGGAGTTATTTATAAAAAGAATGATAAAGAAGCTTACATCGTCACCAACAATCAC

GTTATTAATGGCGCCAGCAAAGTAGATATTCGATTGTCAGATGGGACTAAAGTACCTGGAGAAATTGTCGGAGCT GACACTTTCTCTGATATTGCTGTCGTCAAAATCTCTTCAGAAAAAGTGACAACAGTAGCTGAGTTTGGTGATTCTA GTAAGTTAACTGTAGGAGAAACTGCTATTGCCATCGGTAGCCCGTTAGGTTCTGAATATGCAAATACTGTCACTCA AGGTATCGTATCCAGTCTCAATAGAAATGTATCCTTAAAATCGGAAGATGGACAAGCTATTTCTACAAAAGCCAT CCAAACTGATACTGCTATTAACCCAGGTAACTCTGGCGGCCCACTGATCAATATTCAAGGGCAGGTTATCGGAAT

TACCTCAAGTAAAATTGCTACAAATGGAGGAACATCTGTAGAAGGTCTTGGTTTCGCAATTCCTGCAAATGATGCT ATCAATATTATTGAACAGTTAGAAAAAAACGGAAAAGTGACGCGTCCAGCTTTGGGAATCCAGATGGTTAATTTA TCTAATGTGAGTACAAGCGACATCAGAAGACTCAATATTCCAAGTAATGTTACATCTGGTGTAATTGTTCGTTCGG TACAAAGTAATATGCCTGCCAATGGTCACCTTGAAAAATACGATGTAATTACAAAAGTAGATGACAAAGAGATTG CTTCATCAACAGACTTACAAAGTGCTCTTTACAACCATTCTATCGGAGACACCATTAAGATAACCTACTATCGTAA

CGGGAAAGAAGAAACTACCTCTATCAAACTTAACAAGAGTTCAGGTGATTTAGAATCTTAA

MEANMKHLKTFYKKWFQLLVVIVISFFSGALGSFSITQLTQKSSVNNSNNNSTITQTAYKNENSTTQAVNKVKDAVVSV ITYSANRQNSVFGNDDTDTDSQRISSEGSGVIYKKND EAYIVTNNHVINGASKVDIRLSDGTKVPGEIVGADTFSDIAV VKISSE VTTVAEFGDSSKLTVGETAIAIGSPLGSEYANTVTQGIVSSLNRNVSLKSEDGQAISTKAIQTDTAINPGNSGGP LINIQGQVIGITSSKIATNGGTSVEGLGFAIPANDAINllEQLE NGKVTRPALGIQMVNLSNVSTSDIRRLNIPSNVTSGVIV RSVQSNMPANGHLEKYDVITKVDDKEIASSTDLQSALYNHSIGDTIKITYYRNGKEETTSIK NKSSGDLESZ

ID15 939bp

ATGGCAGAAATTTATCTAGCAGGTGGTTGTTTTTGGGGCCTAGAGGAATATTTTTCACGCATTTCTGGAGTGCTAG AAACCAGTGTTGGCTACGCTAATGGTCAAGTCGAAACGACCAATTACCAGTTGCTCAAGGAAACAGACCATGCAG AAACGGTCCAAGTGATTTACGATGAGAAGGAAGTGTCACTCAGAGAGATTTTACTTTATTATTTCCGAGTTATCGA TCCTCTATCTATCAATCAACAAGGGAATGACCGTGGTCGCCAATATCGAACTGGGATTTATTATCAGGATGAAGC AGATTTGCCAGCTATCTACACAGTGGTGCAGGAGCAGGAACGCATGCTGGGTCGAAAGATTGCAGTAGAAGTGGA

GCAATTACGCCACTACATTCTGGCTGAAGACTACCACCAAGACTATCTCAGGAAGAATCCTTCAGGTTACTGTCAT ATCGATGTGACCGATGCTGATAAGCCATTGATTGATGCAGCAAACTATGAAAAGCCTAGTCAAGAGGTGTTGAAG GCCAGTCTATCTGAAGAGTCTTATCGTGTCACACAAGAAGCTGCTACAGAGGCTCCATTTACCAATGCCTATGACC AAACCTTTGAAGAGGGGATTTATGTAGATATTACGACAGGTGAGCCACTCTTTTTTGCCAAGGATAAGTTTGCTTC AGGTTGTGGTTGGCCAAGTTTTAGCCGTCCGATTTCCAAAGAGTTGATTCATTATTACAAGGATCTGAGCCATGGA

ATGGAGCGAATTGAAGTTCGTTCTCGTTCAGGCAGTGCTCACTTGGGTCATGTTTTCACAGATGGACCGCGGGAGT TAGGCGGCCTCCGTTACTGTATCAATTCTGCTTCTTTACGCTTTGTGGCCAAGGATGAGATGGAAAAAGCAGGATA TGGCTATCTATTGCCTTACTTAAACAAATAA MAEIYLAGGCFWGLEEYFSRISGVLETSVGYANGQVETTNYQLLKETDHAETVQVIYDEKEVSLREILLYYFRVIDPLSI

NQQGNDRGRQYRTGIYYQDEADLPAIYTVVQEQERMLGRKIAVEVEQLRHYILAEDYHQDYLRKNPSGYCHIDVTDA DKPLIDAANYEKPSQEVLKASLSEESYRVTQEAATEAPFTNAYDQTFEEGIYVDITTGEPLFFAKDKFASGCGWPSFSRPI SKELIHYYKDLSHGMERIEVRSRSGSAHLGHVFTDGPRELGG RYCINSASLRFVAKDEMEKAGYGYLLPYLNKZ ID17 870bp

ATGAAGATTATTGTACCTGCAACCAGTGCCAATATCGGGCCAGGTTTTGACTCGGTCGGTGTAGCTGTAACCAAGT

ATCTTCAAATTGAGGTCTGCGAAGAACGAGATGAGTGGCTGATTGAACACCAGATTGGCAAATGGATTCCACATG

ACGAGCGTAATCTCTTGCTCAAAATCGCTTTGCAAATTGTACCAGACTTGCAACCAAGACGCTTGAAAATGACCA GTGATGTCCCTTTGGCGCGCGGTTTGGGTTCTTCCAGCTCGGTTATCGTTGCTGGGATTGAACTAGCCAACCAACT

GGGTCAACTCAACTTATCAGACCATGAAAAATTGCAGTTAGCGACCAAGATTGAAGGGCATCCTGACAATGTGGC TCCAGCCATTTATGGTAATCTCGTTATTGCAAGTTCTGTTGAAGGGCAAGTCTCTGCTATCGTAGCAGACTTTCCA GAGTGTGATTTTCTAGCTTACATTCCAAACTATGAATTACGTACTCGCGACAGCCGTAGTGTCTTGCCTAAAAAAT TGTCTTATAAGGAAGCTGTTGCTGCAAGTTCTATCGCCAATGTAGCGGTTGCTGCCTTGTTGGCAGGAGACATGGT GACCGCTGGGCAAGCAATCGAGGGAGACCTCTTCCATGAGCGCTATCGTCAGGACTTGGTAAGAGAATTTGCGAT

GATTAAGCAAGTGACCAAAGAAAATGGGGCCTATGCAACCTACCTTTCTGGTGCTGGGCCGACAGTTATGGTTCT GGCTTCTCATGACAAGATGCCAACAATTAAGGCAGAATTGGAAAAGCAACCTTTCAAAGGAAAACTGCATGACTT GAGAGTTGATACCCAAGGTGTCCGTGTAGAAGCAAAATAA MKIIVPATSANIGPGFDSVGVAVTKYLQIEVCEERDEWLIEHQIGKWIPHDERNLLLKIALQIVPDLQPRRLKMTSDVPLA

RGLGSSSSVIVAGIELANQLGQLNLSDHEKLQLATKIEGHPDNVAPAIYGNLVIASSVEGQVSAIVADFPECDFLAYIPNY ELRTRDSRSVLPKKLSYKEAVAASSIANVAVAALLAGDMVTAGQAIEGDLFHERYRQDLVREFAMIKQVTKENGAYAT YLSGAGPTVMVLASHDKMPTIKAELEKQPFKGKLHDLRVDTQGVRVEAKZ ID20 564bp

ATGAAATATCACGATTACATCTGGGATTTAGGTGGAACTTTACTGGATAATTATGAAACTTCAACAGCTGCATTTG TTGAAACATTGGCACTGTATGGTATCACACAAGACCATGACAGTGTCTATCAAGCTTTAAAGGTTTCTACTCCTTT TGCGATTGAGACATTCGCTCCCAATTTAGAGAATTTTTTAGAAAAGTACAAGGAAAATGAAGCCAGAGAGCTTGA ACACCCGATTTTATTTGAAGGAGTTTCTGACCTATTGGAAGACATTTCAAATCAAGGTGGCCGTCATTTTTTGGTC

TCTCATCGAAATGATCAGGTTTTGGAAATTTTAGAAAAAACCTCTATAGCAGCTTATTTTACAGAAGTGGTGACTT CTAGCTCAGGCTTTAAGAGAAAGCCAAATCCCGAATCCATGCTTTATTTAAGAGAAAAGTATCAGATTAGCTCTG GTCTTGTCATTGGTGATCGGCCGATTGATATCGAAGCAGGTCAAGCTGCAGGACTTGATACCCACTTGTTTACCAG TATCGTGAATTTAAGACAAGTATTAGACATATAA

MKYHDYIWDLGGTLLDNYETSTAAFVETLALYGITQDHDSVYQALKVSTPFAIETFAPNLENFLEKYKENEARELEHPI LFEGVSDLLEDISNQGGRHFLVSHRNDQVLEILEKTSIAAYFTEVVTSSSGFKRKPNPES LYLREKYQISSGLVIGDRPID IEAGQAAGLDTHLFTSIVNLRQVLDIZ ID21 1875bp

ATGACAGAAGAAATCAAAAATCTGCAGGCACAGGATTATGATGCCAGTCAAATTCAAGTTTTAGAGGGCTTAGAG GCTGTTCGTATGCGTCCAGGGATGTACATTGGATCAACCTCAAAAGAAGGTCTTCACCATCTAGTCTGGGAAATTG TTGATAACTCAATTGACGAGGCCTTGGCAGGATTTGCCAGCCATATTCAAGTTTTTATTGAGCCAGATGATTCGAT TACTGTTGTGGATGATGGGCGTGGTATCCCAGTCGATATTCAGGAAAAAACAGGCCGTCCTGCTGTTGAGACCGT CTTTACAGTCCTTCACGCTGGAGGAAAGTTCGGCGGTGGTGGATACAAGGTTTCAGGTGGTCTTCACGGGGTGGG GTCGTCAGTAGTTAATGCCCTTTCCACTCAATTAGACGTTCATGTTCACAAAAATGGTAAGATTCATTACCAAGAA TACCGTCGTGGTCATGTTGTCGCAGATCTTGAAATAGTTGGAGATACGGATAAAACAGGAACAACTGTTCACTTC ACACCGGACCCAAAAATCTTCACTGAAACAACAATCTTTGATTTTGATAAATTAAATAAACGGATTCAAGAGTTG GCCTTTCTAAATCGCGGTCTTCAAATTTCAATTACAGATAAGCGCCAAGGTTTGGAACAAACCAAGCATTATCATT

ATGAAGGTGGGATTGCTAGTTACGTTGAATATATCAACGAGAACAAGGATGTAATCTTTGATACACCAATCTATA CAGACGGTGAGATGGATGATATCACAGTTGAGGTAGCCATGCAGTACACAACTGGTTACCATGAAAATGTCATGA GTTTCGCCAATAATATTCATACCCATGAAGGTGGAACACATGAACAAGGTTTCCGTACAGCCTTGACACGTGTTAT CAACGATTATGCTCGTAAAAATAAGTTACTGAAAGACAATGAAGATAATTTAACAGGGGAAGATGTTCGCGAAGG CTTAACTGCAGTTATCTCAGTTAAACACCCAAATCCACAGTTTGAAGGACAAACCAAGACCAAATTGGGAAATAG

CGAAGTGGTCAAGATTACCAATCGCCTCrTCAGTGAAGCTTTCTCCGATTTCCTCATGGAAAATCCACAGATTGCC AAACGTATCGTAGAAAAAGGAATTTTGGCTGCCAAGGCTCGTGTGGCTGCCAAGCGTGCGCGTGAAGTCACACGT AAAAAATCTGGTTTGGAAATTTCCAACCTTCCAGGGAAACTAGCAGACTGTTCTTCTAATAACCCTGCTGAAACAG AACTCTTCATCGTCGAAGGAGACTCAGCTGGTGGATCAGCCAAATCTGGTCGTAACCGTGAGTTTCAGGCTATCCT TCCAATTCGCGGTAAGATTTTGAACGTTGAAAAAGCAAGTATGGATAAGATTCTAGCCAACGAAGAAATTCGTAG

TCTTTTCACAGCCATGGGAACAGGATTTGGCGCAGAATTTGATGTT CGAAAGCCCGTTACCAAAAACTCGTTTTG ATGACCGATGCCGATGTCGATGGAGCCCACATTCGTACCCTTCTTTTAACCTTGATTTATCGTTATATGAAACCAA TCCTAGAAGCTGGTTATGTTTATATTGCCCAACCACCAATCTATGGTGTCAAGGTTGGAAGCGAGATTAAAGAATA TATCCAGCCGGGTGCAGATCAAGAAATCAAACTCCAAGAAGCTTTAGCCCGTTATAGTGAAGGTCGTACCAAACC GACTATTCAGCGTTATAAGGGGCTAGGTGAAATGGACGATCATCAGCTGTGGGAAACAACCATGGATCCCGAACA

TCGCTTGATGGCTAGAGTTTCTGTAGATGATGTGCAGAAGCAGATAAAATCTTTGATATGTTGA

MTEEIKNLQAQDYDASQIQVLEGLEAVRMRPGMYIGSTSKEGLHHLVWEIVDNSIDEALAGFASHIQVFIEPDDSITVVD DGRGIPVDIQEKTGRPAVETVFTVLHAGGKFGGGGYKVSGGLHGVGSSVVNALSTQLDVHVHKNGKIHYQEYRRGHV VADLEIVGDTDKTGTTVHFTPDPKIFTETTIFDFDKLNKRIQELAFLNRGLQISITD RQGLEQTKHYHYEGGIASYVEYI

NENKDVIFDTPIYTDGEMDDITVEVAMQYTTGYHENVMSFANNIHTHEGGTHEQGFRTALTRVINDYARKNKLLKDN EDNLTGEDVREGLTAVISVKHPNPQFEGQTKTKLGNSEVVKITNRLFSEAFSDFLMENPQIAKRIVEKGILAAKARVAAK RAREVTRKKSGLEISNLPGKLADCSSNNPAETELFIVEGDSAGGSAKSGRNREFQAILPIRGKILNVEKASMDKILANEEI RSLFTAMGTGFGAEFDVS ARYQKLVLMTDADVDGAHIRTLLLTLIYRYMKPILEAGYVYIAQPPIYGV VGSEI EYI QPGADQEIKLQEALARYSEGRTKPTIQRYKGLGEMDDHQLWETTMDPEHRLMARVSVDDVQKQIKSLICZ

ID54 1446bp

ATGAGTAGACGTTTTAAAAAATCACGTTCACAGAAAGTGAAGCGAAGTGTTAATATAGTTTTGCTGACTATTTATT TAT GTTAGTTTGTTΓΓTTATTGTTCTTAATCTTTAAGTACAATATCCTTGCTTTTAGATATCTTAATC AGTGGT^

CTGCGTTAGTCCTACTAGTTGCCTTGGTAGGGCTACTCTTGATTATCTATAAAAAAGCTGAAAAGTTTACTATTTTT CTGTTGGTGTTCTCTATCCTTGTCAGCTCTGTGTCGCTCTTTGCAGTACAGCAGTTTGTTGGACTGACCAATCGTTT AAATGCGACTTCTAATTACTCAGAATATTCAATCAGTGTCGCTGTTTTAGCAGATAGTGAGATCGAAAATGTTACG CAACTGACGAGTGTGACAGCACCGACTGGGACTAATAATGAAAATATTCAGAAATTACTAGCTGATATCAAGTCA AGTCAGAATACCGATTTGACGGTCAACCAGAGTTCGTCTTACTTGGCAGCTTACAAGAGTTTGATTGCAGGGGAG

ACTAAGGCCATTGTCCTAAATAGTGTCTTTGAAAACATCATCGAGTCAGAGTATCCAGACTACGCATCGAAGATA AAAAAGATTTATACTAAGGGATTCACTAAAAAAGTAGAAGCTCCTAAGACGTCTAAGAGTCAGTCTTTCAATATC TATGTTAGTGGAATTGACACCTATGGTCCTATTAGTTCGGTGTCGCGATCAGATGTCAACATCCTGATGACTGTCA ATCGAGATACCAAGAAAATCCTCTTGACCACAACGCCACGTGATGCCTATGTACCAATCGCAGATGGTGGAAATA ATCAAAAAGATAAATTGACTCATGCGGGCATTTATGGAGTTGATTCGTCCATTCACACCTTAGAAAATCTCTATGG

AGTGGATATCAATTACTATGTGCGATTGAACTTCACTTCGTTTTTGAAATTGATTGATTTGTTGGGTGGAATTGATG TTTATAATGATCAAGAATTTACTGCCCATACGAATGGAAAGTATTACCCTGCAGGCAATGTTCATCTTGATTCAGA ACAGGCTCTCGGTTTTGTTCGTGAGCGCTACTCCCTAGCAGATGGCGATCGTGACCGCGGGCGCCATCAACAAAA GGTGATTGTGGCTATCCTTCAAAAATTAACGTCAACCGAAGTGCTGAAAAATTATAGTACGATCATTAATAGCTTG CAAGATTCTATCCAAACAAATATGCCACTTGAGACCATGATAAATTTGGTCAATGCTCAGTTAGAAAGTGGAGGG

AATTATAAAGTAAATTCTCAAGATTTAAAAGGGACAGGTCGGATGGATCTTCCTTCTTATGCAATGCCAGACAGTA ACCTCTATGTGATGGAAATAGATGATAGTAGTTTAGCTGTAGTTAAAGCAGCTATACAGGATGTGATGGAGGGTA

GATGA MSRRFKKSRSQKVKRSVNIVLLTIYLLLVCFLLFLIFKYNILAFRYLNLVVTALVLLVALVGLLLIIYKKAEKFTIFLLVFS

ILVSSVSLFAVQQFVGLTNRLNATSNYSEYSISVAV ADSEIENVTQLTSVTAPTGTNNENIQKLLADIKSSQNTDLTVNQ SSSYLAAYKSLIAGETKAIVLNSVFENIIESEYPDYASKIKKIYTKGFTKKVEAPKTS SQSFNIYVSGIDTYGPISSVSRSDV NILMTVNRDTKKILLTTTPRDAYVPIADGGNNQ DKLTHAGIYGVDSSIHTLENLYGVDINYYVRLNFTSFLKLIDLLGG IDVYNDQEFTAHTNGKYYPAGNVHLDSEQALGFVRERYSLADGDRDRGRHQQKVIVAILQKLTSTEVLKNYSTIINSLQ DSIQTNMPLETMINLVNAQLESGGNYKVNSQDLKGTGRMDLPSYAMPDSNLYVMEIDDSSLAVVKAAIQDVMEGRZ

ID55 732bp ATGATAGACATCCATTCGCATATCGTTTTTGATGTAGATGACGGTCCCAAGTCAAGAGAGGAAAGCAAGGCTCTC TTGGCAGAATCCTACAGACAGGGGGTGCGAACCATTGTTTCTACCTCTCACCGTCGCAAGGGCATGTTTGAAACTC CGGAAGAGAAGATAGCAGAAAACTTTCTTCAGGTTCGGGAAATAGCTAAGGAAGTGGCGAGTGACTTGGTCATTG CTTACGGGGCTGAAATTTATTACACACCAGATGTTCTGGATAAGCTGGAAAAAAAGCGGATTCCGACCCTCAATG ATAGTCGTTATGCCTTGATAGAGTTTAGTATGAACACTCCTTATCGCGATATTCATAGCGCCTTGAGCAAGATCTT

GATGTTGGGAATTACTCCAGTCATTGCCCACATTGAGCGCTATGATGCTCTTGAAAATAATGAAAAACGCGTTCGA GAACTGATCGATATGGGCTGT ACACGCAAGTAAATAGTTCACATGTCCTCAAACCCAAACTTTTTGGCGAACGTT ATAAATTCATGAAAAAAAGAGCTCAGTATTTTTTAGAGCAGGATTTGGTTCATGTCATTGCAAGTGATATGCACAA TCTAGACGGTAGACCTCCTCATATGGCAGAAGCATATGACCTTGTTACCCAAAAATACGGAGAAGCGAAGGCTCA GGAACTTTTTATAGACAATCCTCGAAAAATTGTAATGGATCAACTAATTTAG

MIDIHSHIVFDVDDGPKSREESKALLAESYRQGVRTIVSTSHRRKGMFETPEEKIAENFLQVREIAKEVASDLVIAYGAEI YYTPDVLDKLEKKRIPTLNDSRYALIEFSMNTPYRDIHSALSKILMLGITPVIAHIERYDALENNEKRVRELIDMGCYTQV NSSHVLKPKLFGERYKFMKKRAQYFLEQDLVHVIASDMHNLDGRPPHMAEAYDLVTQKYGEAKAQELFIDNPRKIVM DQLIZ

ID58 3990bp

TTGATTTATATAATCGCTATCAATATAACAATGCAATCAGGAGGTTTTGCAATGAAACATGAAAAACAACAGCGT TTTTCTATTCGTAAATACGCTGTAGGAGCAGCTTCTGTTCTAATTGGATTTGCCTTCCAAGCACAGACTGTTGCAG

CCGATGGAGTTACTCCTACTACTACAGAAAACCAACCGACCATCCATACGGTTTCTGATTCCCCTCAATCATCCGA AAATCGGACTGAGGAAACACCTAAAGCAGTGCTTCAACCAGAAGCTCCAAAAACTGTAGAAACAGAAACTCCAG CTACTGATAAGGTAGCTAGTCTTCCAAAAACAGAAGAAAAACCACAAGAGGAAGTTAGTTCAACTCCTAGTGATA AAGCAGAAGTGGTAACTCCAACTTCTGCTGAAAAAGAAACTGCTAATAAAAAGGCAGAAGAAGCTAGCCCTAAA AAGGAAGAAGCGAAAGAGGTTGATTCTAAAGAGTCAAATACAGACAAGACTGACAAGGATAAACCAGCTAAAAA

AGATGAAGCGAAAGCAGAGGCTGACAAACCGGCAACAGAGGCAGGAAAGGAACGTGCTGCAACTGTAAATGAAA AACTAGCGAAAAAGAAAATTGTTTCTATTGATGCTGGACGTAAATATTTCTCACCAGAACAGCTCAAGGAAATCA TCGATAAAGCGAAACATTATGGCTACACTGATTTACACCTATTAGTCGGAAATGATGGACTCCGTTTCATGTTGGA CGATATGAGCATCACAGCTAACGGCAAGACCTATGCCAGTGACGATGTCAAACGCGCCATTGAAAAAGGTACAAA TGATTATTACAACGATCCAAACGGCAATCACTTAACAGAAAGTCAAATGACAGATCTGATTAACTATGCCAAAGA

TAAAGGTATCGGTCTCATTCCGACAGTAAATAGTCCTGGACACATGGATGCGATTCTCAATGCCATGAAAGAATT GGGAATCCAAAACCCTAAC ITAGCTATTTTGGGAAGAAATCAGCCCGTACTGTCGATCTTGACAACGAACAAGC TGTCGCTTT ACAAAAGCCCTTATCGACAAGTATGCTGCTTATTTCGCGAAAAAGACTGAAATCTTCAACATCGGA CTTGATGAATATGCCAATGATGCGACAGATGCTAAAGGTTGGAGTGTGCTTCAAGCTGATAAATACTATCCAAAC GAAGGCTACCCTGTAAAAGGCTATGAAAAATTTATTGCCTACGCCAATGACCTCGCTCGTATTGTAAAATCGCAC

GGTCTCAAACCAATGGCΓTTTAACGACGGTATCTACTACAATAGCGACACAAGCITΓGGTAGTTTTGACAAAGAC ATCATCGTTTCTATGTGGACTGGTGGTTGGGGAGGCTACGATGTCGCTTCTTCTAAACTACTAGCTGAAAAAGGTC ACCAAATCCTTAATACCAATGATGCTTGGTACTACGTTCTTGGACGAAACGCTGATGGCCAAGGCTGGTACAATCT CGATCAGGGGCTCAATGGTATTAAAAACACACCAATCACTTCTGTACCAAAAACAGAAGGAGCTGATATCCCAAT CATCGGTGGTATGGTAGCTGCTTGGGCTGACACTCCATCTGCACGTTATTCACCATCACGCCTCTTCAAACTCATG

CGTCATTTTGCAAATGCCAACGCTGAATACTTCGCAGCTGATTATGAATCTGCAGAGCAAGCACTTAACGAGGTA CCAAAAGACCTGAACCGTTATACTGCAGAAAGCGTCACGGCCGTAAAAGAAGCTGAAAAAGCTATTCGCTCTCTC GATAGCAACCTTAGCCGTGCCCAACAAGATACGATTGATCAAGCCATTGCTAAACTTCAAGAAACTGTCAACAAC TTGACCCTCACGCCTGAAGCTCAAAAAGAAGAAGAAGCTAAACGTGAGGTTGAAAAACTTGCCAAAAACAAGGT AATCTCAATCGATGCTGGACGCAAATACTTTACTCTGAACCAGCTCAAACGCATCGTAGACAAGGCCAGTGAGCT

CGGATATTCTGATGTCCATCTCCTTCTAGGAAATGACGGACTTCGCTTTCTACTCGATGATATGACCATTACTGCC AACGGAAAAACCTATGCTAGTGATGACGTTAAAAAAGCTATTATCGAAGGAACTAAAGCTTACTACGACGATCCA AACGGTACTGCACTAACACAGGCAGAAGTAACAGAGCTAATTGAATACGCTAAATCTAAGGACATCGGTCTCATC CCAGCTATTAACAGTCCAGGTCACATGGATGCTATGCTGGTTGCCATGGAAAAATTAGGTATTAAAAATCCTCAA GCCCACTTTGATAAAGTTTCAAAAACAACTATGGACTTGAAAAACGAAGAAGCGATGAACTTTGTAAAAGCCCTC ATCGGTAAATACATGGACΓTCTTTGCAGGTAAAACAAAGATTTTCAACTTTGGTACTGACGAATACGCCAACGAT GCGACTAGTGCCCAAGGCTGGTACTACCTCAAGTGGTATCAACTCTATGGCAAATTTGCCGAATATGCCAACACC CTCGCAGCTATGGCCAAAGAAAGAGGGCTTCAACCAATGGCCTTCAACGATGGCTTCTACTATGAAGACAAGGAC GATGTTCAGTTTGACAAAGATGTCTTGATTTCTTACTGGTCTAAAGGCTGGTGGGGATATAACCTCGCATCACCTC AATACCTAGCAAGCAAAGGCTATAAATTCTTGAATACCAACGGTGACTGGTACTACATTCTTGGTCAAAAACCAG

AAGATGGTGGTGGTTTCCTCAAGAAAGCTATTGAGAATACTGGAAAAACACCATTCAATCAACTAGCTTCTACCA AATATCCTGAAGTAGATCTTCCAACAGTCGGAAGTATGCTTTCAATCTGGGCAGATAGACCAAGCGCTGAATACA AGGAAGAGGAAATCTTTGAACTCATGACTGCCTTTGCAGACCACAACAAAGACTACTTTCGTGCTAATTATAATG CTCTCCGCGAAGAATTAGCTAAAATTCCTACAAACTTAGAAGGATATAGTAAAGAAAGTCTTGAGGCCCTTGACG CAGCTAAAACAGCTCTAAATTACAACCTCAACCGTAATAAACAAGCTGAGCTTGACACGCTTGTAGCCAACCTAA

AAGCCGCTCTTCAAGGCCTCAAACCAGCTGTAACTCATTCAGGAAGCCTAGATGAAAATGAAGTGGCTGCCAATG TTGAAACCAGACCAGAACTCATCACAAGAACTGAAGAAATTCCATTTGAAGTTATCAAGAAAGAAAATCCTAACC TCCCAGCCGGTCAGGAAAATATTATCACAGCAGGAGTCAAAGGTGAACGAACTCATTACATCTCTGTACTCACTG AAAATGGAAAAACAACAGAAACAGTCCTTGATAGCCAGGTAACCAAAGAAGTTATAAACCAAGTGGTTGAAGTT GGCGCTCCTGTAACTCACAAGGGTGATGAAAGTGGTCTTGCACCAACTACTGAGGTAAAACCTAGACTGGATATC

SUBSTΓΓUTE SHEET (RULE 26) CAAGAAGAAGAAATTCCATTTACCACAGTGACTTGTGAAAATCCACTCTTACTCAAAGGAAAAACACAAGTCATT ACTAAGGGCGTCAATGGACATCGTAGCAACTTCTACTCTGTGAGCACTTCTGCCGATGGTAAGGAAGTGAAAACA CTTGTAAATAGTGTCGTAGCACAGGAAGCCGTTACTCAAATAGTCGAAGTCGGAACTATGGTAACACATGTAGGC GATGAAAACGGACAAGCCGCTATTGCTGAAGAAAAACCAAAACTAGAAATCCCAAGCCAACCAGCTCCATCAAC TGCTCCTGCTGAGGAAAGCAAAGTTCTTCCTCAAGATCCAGCTCCTGTGGTAACAGAGAAAAAACTTCCTGAAAC

AGGAACTCACGATTCTGCAGGACTAGTAGTCGCAGGACTCATGTCCACACTAGCAGCCTATGGACTCACTAAAAG AAAAGAAGACTAA

MIYIIAINITMQSGGFAMKHEKQQRFSIRKYAVGAASVLIGFAFQAQTVAADGVTPTTTENQPTIHTVSDSPQSSENRTEE TPKAVLQPEAPKTVETETPATDKVASLPKTEEKPQEEVSSTPSDKAEVVTPTSAEKETANK AEEASPKKEEAKEVDSKE

SNTDKTDKDKPAKKDEAKAEADKPATEAGKERAATVNEKLAKKKIVSIDAGRKYFSPEQL EIIDKAKHYGYTDLHLL VGNDGLRFMLDDMSITANGKTYASDDVKRAIEKGTNDYYNDPNGNHLTESQMTDLINYAKDKGIGLIPTVNSPGHMD AILNAMKELGIQNPNFSYFGKKSARTVDLDNEQAVAFTKALIDKYAAYFAKKTEIFNIGLDEYANDATDAKGWSVLQA DKYYPNEGYPV GYEKFIAYANDLARIVKSHGLKPMAFNDGIYYNSDTSFGSFDKDIIVSMWTGGWGGYDVASSKLLA E GHQILNTNDAWYYVLGRNADGQGWYNLDQGLNGIKNTPITSVPKTEGADIPIIGGMVAAWADTPSARYSPSRLFKL

MRHFANANAEYFAADYESAEQALNEVPKDLNRYTAESVTAV EAEKAIRSLDSNLSRAQQDTIDQAIA LQETVNNLT LTPEAQKEEEAKREVEKLAKN VISIDAGRKYFTLNQLKRIVDKASELGYSDVHLLLGNDGLRFLLDDMTITANGKTYA SDDVKKAIIEGTKAYYDDPNGTALTQAEVTELIEYAKSKDIGLIPAINSPGHMDAMLVAMEKLGIKNPQAHFDKVSKTT MDLKNEEAMNFVKALIGKYMDFFAGKTKIFNFGTDEYANDATSAQGWYYL WYQLYGKFAEYANTLAAMAKERGL QPMAFNDGFYYEDKDDVQFD DVLISY SKGWWGYNLASPQYLAS GYKFLNTNGDWYYILGQ PEDGGGFLKKAI

ENTGKTPFNQLASTKYPEVDLPTVGSMLSIWADRPSAEYKEEEIFELMTAFADHNKDYFRANYNALREELAKIPTNLEG YSKESLEALDAAKTALNYNLNRNKQAELDTLVANLKAALQGLKPAVTHSGSLDENEVAANVETRPELITRTEEIPFEVI KKENPNLPAGQENIITAGVKGERTHYISVLTENGKTTETVLDSQVTKEVINQVVEVGAPVTHKGDESGLAPTTEV PRL DIQEEEIPFTTVTCENPLLLKGKTQVITKGVNGHRSNFYSVSTSADGKEVKTLVNSVVAQEAVTQIVEVGTMVTHVGDE NGQAAIAEEKPKLEIPSQPAPSTAPAEESKVLPQDPAPVVTEKKLPETGTHDSAGLVVAGLMSTLAAYGLTKRKEDZ

ID122 825bp

ATGAACAAAAAAACAAGACAGACACTAATCGGACTGCTAGTGTTATTGCTTTTGTCTACAGGGAGCTATTATATC AAGCAGATGCCGTCGGCACCTAATAGTCCCAAAACCAATCTTAGTCAGAAAAAACAAGCGTCTGAAGCTCCTAGT CAAGCATTGGCAGAGAGTGTCTTAACAGACGCAGTCAAGAGTCAAATAAAGGGGAGTCTGGAGTGGAATGGCTC AGGTGCTTTTATCGTCAATGGTAATAAAACAAATCTAGATGCCAAGGTTTCAAGTAAGCCCTACGCTGACAATAA AACAAAGACAGTGGGCAAGGAAACTGTTCCAACCGTAGCTAATGCCCTCTTGTCTAAGGCCACTCGTCAGTACAA GAATCGTAAAGAAACTGGGAATGGTTCAACTTCTTGGACTCCTCCAGGTTGGCATCAGGTCAAGAATCTAAAGGG CTCTTATACCCATGCAGTCGATAGAGGTCATTTGTΓAGGCTATGCCTTAATCGGTGGTTTGGATGGTTTTGATGCCT

CAACAAGCAATCCTAAAAACATTGCTGTTCAGACAGCCTGGGCAAATCAGGCACAAGCCGAGTATTCGACTGGTC AAAACTACTATGAAAGCAAGGTGCGTAAAGCCTTGGACCAAAACAAGCGTGTCCGTTACCGTGTAACCCTTTACT ACGCTTCAAACGAGGATTTAGTTCCCTCAGCTTCACAGATTGAAGCCAAGTCTTCGGATGGAGAATTGGAATTCA ATGTTCTAGTTCCCAATGTTCAAAAGGGACTTCAACTGGATTACCGAACTGGAGAAGTAACTGTAACTCAGTAA

MNKKTRQTLIGLLVLLLLSTGSYYIKQMPSAPNSPKTNLSQKKQASEAPSQALAESVLTDAVKSQIKGSLEWNGSGAFIV NGNKTNLDAKVSSKPYADNKTKTVGKETVPTVANALLSKATRQYKNRKETGNGSTSWTPPGWHQVKNLKGSYTHAV DRGHLLGYALIGGLDGFDASTSNPKNIAVQTAWANQAQAEYSTGQNYYES VRKALDQNKRVRYRVTLYYASNEDL VPSASQIEAKSSDGELEFNVLVPNVQKGLQLDYRTGEVTVTQZ

ID123 225bp

GTGCTAAGATTCAGCGGATTGAGGCAAGTGATGAAGATGAATAAGAAATCAAGCTACGTAGTCAAGCGTTTACTT TTAGTCATCATAGTACTGATTTTAGGTACTCTGGCTCTAGGAATCGGTTTAATGGTAGGTTATGGAATCTTGGGCA AGGGTCAAGATCCATGGGCTATCCTGTCTCCAGCAAAATGGCAGGAATTGATTCATAAATTTACAGGAAATTAG

VLRFSGLRQVMKMNKKSSYVVKRLLLVIIVLILGTLALGIGLMVGYGILGKGQDPWAILSPAKWQELIHKFTGNZ

Claims

CLAIMS:
1. A Streptococcus pneumoniae protein or polypeptide having a sequence selected from those shown in table 1.
2. A Streptococcus pneumoniae protein or polypeptide having a sequence selected from those shown in table 2.
3. A protein or polypeptide as claimed in claim 1 or claim 2 provided in substantially pure form.
4. A protein or polypeptide which is substantially identical to one defined in any one of claims 1 to 3.
5. A homologue or derivative of a protein or polypeptide as defined in any one of claims 1 to 4.
6. An antigenic and/or immunogenic fragment of a protein or polypeptide as defined in Tables 1-3.
7. A nucleic acid molecule comprising or consisting of a sequence which is:
(i) any of the DNA sequences set out in Table 1 or their RNA equivalents;
(ii) a sequence which is complementary to any of the sequences of (i); (iii) a sequence which codes for the same protein or polypeptide, as those sequences of (i) or (ii);
(iv) a sequence which is substantially identical with any of those of (i), (ii) and (iii);
(v) a sequence which codes for a homologue, derivative or fragment of a protein as defined in Table 1.
8. A nucleic acid molecule comprising or consisting of a sequence which is:
(i) any of the DNA sequences set out in Table 2 or their RNA equivalents;
(ii) a sequence which is complementary to any of the sequences of (i);
(iii) a sequence which codes for the same protein or polypeptide, as those sequences of (i) or (ii);
(iv) a sequence which is substantially identical with any of those of (i), (ii) and (iii);
(v) a sequence which codes for a homologue, derivative or fragment of a protein as defined in Table 2.
9. The use of a protein or polypeptide having a sequence selected from those shown in Tables 1-3, or homologues, derivatives and/or fragments thereof, as an immunogen and/or antigen.
10. An immunogenic and/or antigenic composition comprising one or more proteins or polypeptides selected from those whose sequences are shown in Tables 1- 3, or homologues or derivatives thereof, and/or fragments of any of these.
11. An immunogenic and/or antigenic composition as claimed in claim 10 which is a vaccine or is for use in a diagnostic assay.
12. A vaccine as claimed in claim 11 which comprises one or more additional components selected from excipients, diluents, adjuvants or the like.
13. A vaccine composition comprising one or more nucleic acid sequences as defined in Tables 1-3.
14. A method for the detection/diagnosis of S.pneumoniae which comprises the step of bringing into contact a sample to be tested with at least one protein or polypeptide as defined in Tables 1-3, or homologue, derivative or fragment thereof.
15. An antibody capable of binding to a protein or polypeptide as defined in Tables 1-3, or for a homologue, derivative or fragment thereof.
16. An antibody as defined in claim 15 which is a monoclonal antibody.
17. A method for the detection/diagnosis of S.pneumoniae which comprises the step of bringing into contact a sample to be tested and at least one antibody as define din claim 15 or claim 16.
18. A method for the detection/diagnosis of S.pneumoniae which comprises the step of bringing into contact a sample to be tested with at least one nucleic acid
SUBSTΓΓUTE SHEET (RULE 26) sequence as defined in claim 7 or claim 8.
19. A method of determining whether a protein or polypeptide as defined in Tables 1-3 represents a potential anti-microbial target which comprises inactivating said protein or polypeptide and determining whether S.pneumoniae is still viable.
20. The use of an agent capable of antagonising, inhibiting or otherwise interfering with the function or expression of a protein or polypeptide as defined in Tables 1-3 in the manufacture of a medicament for use in the treatment or prophylaxis of S.pneumoniae infection
PCT/GB1999/002452 1998-07-27 1999-07-27 NUCLEIC ACIDS AND PROTEINS FROM $i(STREPTOCOCCUS PNEUMONIAE) WO2000006738A2 (en)

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JP2000562520A JP2002521058A (en) 1998-07-27 1999-07-27 Streptococcus pneumoniae-derived nucleic acids and proteins
US09/769,744 US20030134407A1 (en) 1998-07-27 2001-01-26 Nucleic acids and proteins from Streptococcus pneumoniae
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WO2000076540A2 (en) * 1999-06-10 2000-12-21 Med Immune, Inc. Streptococcus pneumoniae proteins and vaccines
WO2002077021A2 (en) * 2001-03-27 2002-10-03 Chiron Srl. Streptococcus pneumoniae proteins and nucleic acids
WO2002079241A2 (en) * 2001-03-30 2002-10-10 Microbial Technics Limited Secreted streptococcus pneumoniae proteins
JP2003526676A (en) * 2000-03-14 2003-09-09 カイロン ベーリング ゲーエムベーハー アンド カンパニー Adjuvant for vaccines
WO2004048575A2 (en) * 2002-11-26 2004-06-10 Id Biomedical Corporation Streptococcus pneumoniae surface polypeptides
US6887480B1 (en) 1999-06-10 2005-05-03 Medimmune, Inc. Streptococcus pneumoniae proteins and vaccines
US7074415B2 (en) 2000-06-20 2006-07-11 Id Biomedical Corporation Streptococcus antigens
US7128918B1 (en) 1998-12-23 2006-10-31 Id Biomedical Corporation Streptococcus antigens
US7262024B2 (en) 2001-12-20 2007-08-28 Id Biomedical Corporation Streptococcus antigens
US7381815B2 (en) 1997-07-02 2008-06-03 Sanofi Parker Limited Nucleic acid and amino acid sequences relating to Streptococcus pneumoniae for diagnostics and therapeutics
WO2009016515A3 (en) * 2007-08-01 2009-08-13 Novartis Ag Compositions comprising pneumococcal antigens
WO2009111337A1 (en) 2008-03-03 2009-09-11 Irm Llc Compounds and compositions as tlr activity modulators
WO2009115508A2 (en) * 2008-03-17 2009-09-24 Intercell Ag Peptides protective against s. pneumoniae and compositions, methods and uses relating thereto
US7608276B2 (en) 2001-03-27 2009-10-27 Novartis Vaccines And Diagnostics Srl Staphylococcus aureus proteins and nucleic acids
EP1950302A3 (en) * 1998-12-23 2010-06-23 ID Biomedical Corporation Streptococcus antigens
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