Means and methods for regulating gene expression

Abstract

ethods for regulating gene expression and production of proteinaceous molecules. Described are methods for producing a proteinaceous molecule in a cell comprising selecting a cell for its suitability for producing the proteinaceous molecule, providing a nucleic acid encoding the proteinaceous molecule with a nucleic acid comprising a STAR (STabilizing Anti-Repression) sequence, expressing the resulting nucleic acid in the cell and collecting the proteinaceous molecule. Providing at least one STAR sequence to a nucleic acid encoding a proteinaceous molecule enhances production (yield) of the proteinaceous molecule by the host cell, increases the proportion of host cells with acceptable expression levels, and/or increases the stability of a gene expression level.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001]This application is a divisional of co-pending U.S. patent application Ser. No. 11/888,568, filed Jul. 31, 2007, now U.S. Pat. No. ______, which application is a divisional of U.S. patent application Ser. No. 11/012,546, filed Dec. 14, 2004, now U.S. Pat. No. 7,267,965, issued Sep. 11, 2007, which application is a continuation of International Patent Application No. PCT/NL03/00410, filed May 30, 2003, published in English as International Patent Publication No. WO 03/106674 on Dec. 24, 2003, which claims the benefit under 35 U.S.C. § 119 of European Patent Application No. EP 02077344.6, filed Jun. 14, 2002, the entirety of each of which are hereby incorporated by reference

STATEMENT ACCORDING TO 37 C.F.R § 1.52(e)(5)-SEQUENCE LISTING SUBMITTED ON COMPACT DISC

[0002]Pursuant to 37 C.F.R. § 1.52(e)(1)(iii), a compact disc containing an electronic version of the Sequence Listing has been submitted concomitant with this application, the contents of which are hereby incorporated by reference. The compact disc contains the file "P60555PC00 final.txt" which is 496 KB, and created on Dec. 14, 2004. A second compact disk is submitted and is an identical copy of the first compact disc (labeled, "copy 1" and "copy 2," respectively).

TECHNICAL FIELD

[0003]The invention relates to the fields of medicine and cellular biology. More specifically, the invention relates to means and methods for regulating gene expression, and production of proteinaceous molecules.

BACKGROUND OF THE INVENTION

[0004]Polypeptide production at industrial scale currently provides many biologically active polypeptides for a variety of uses, including diagnostic and therapeutic pharmaceuticals, industrial catalysts and nourishment. Polypeptides are produced in a variety of host systems, including transgenic animals and plants, microbes, and cultured mammalian cells. In most cases, the host system is modified by recombinant DNA techniques, for instance resulting in introduction into the host cell of a transgene which encodes a polypeptide of interest. Such a transgene typically includes elements that influence the transcription, translation, and/or processing of the transgene's polypeptide coding sequence. A recombinant host is then identified and isolated which has a suitable yield of a polypeptide of interest, and the cell population of this recombinant host is increased to an extent that it can produce the required amount of polypeptide.

[0005]The choice of the host system depends on a number of factors including: (1) the nature and intended use of a polypeptide, and (2) the cost of production. For production of biopharmaceuticals, e.g., therapeutic proteins such as hormones, cytokines, and antibodies, the host system of choice is usually cultured mammalian cells. Considerations with respect to product use and production cost with host cells will be discussed below.

[0006](1) For in vivo therapeutic use, a therapeutic protein must not only have the correct biological activity to alter the course of a disease. It must also do no harm. Most therapeutic proteins are exported from the cell by the secretory pathway. Secreted proteins are modified by a series of post-translational events, including glycosylation, disulfide bond formation, and proteolytic processing. The post-translational modification systems vary among different species and cell types in their detailed mechanisms of action. As a result, the same polypeptide chain can be detectably different when it is produced in different host cells. These differences can be analytical, such as differences in physical properties such as molecular mass, net electrical charge, carbohydrate composition, or structure. The differences can also be functional, affecting for instance the biological activity of the protein itself (catalytic activity, ligand binding characteristics, etc.), and/or its in vivo properties (immunogenicity, biological half life, biodistribution, etc.). Functional differences can, therefore, affect both function and possible side effect(s) of a therapeutic protein. Host cell lines that produce proteins with low efficacy are not suitable for commercial exploitation. Furthermore, host cells which produce modified protein that involves significant side effects in a patient should not be used. These factors are becoming increasingly important considerations during selection of a host cell line for production of a therapeutic protein.

[0007](2) Therapeutic protein production in host cells is an intrinsically costly process. Current methods for industrial production of such proteins often perform poorly, resulting in products that are prohibitively expensive. Poor performance can be due to limitations of protein expression systems and host cell lines currently in use. These limitations mostly have a few specific causes, including (a) failure to identify and isolate recombinant host cell lines that have suitable productivity of proteins (poor predictability), (b) silencing, during the industrial production cycle, of the transgenes that encode proteins (poor stability), and (c) low or incorrect post-translational processing and secretory capacity of the host cell line. These limitations will be considered separately below.

[0008](a) Conventional methods furnish only low frequencies of recombinant host cells that have suitable yields of proteins. Identifying and isolating these rare recombinant cell lines is a laborious and expensive process. The poor predictability of conventional methods means that often a recombinant host cell line is selected for production that has sub-optimal productivity characteristics, simply because a superior recombinant cell line was not identified and isolated during the selection process.

[0009](b) Transgenes are often subject to silencing during cultivation of recombinant host cells. Silencing acts by suppressing transcription of a transgene. Detailed mechanisms of silencing are still not known, and different conventional methods are prone to different kinds of silencing phenomena. With one phenomenon, an individual transgene is silenced by formation of transcriptionally refractory heterochromatin at the transgenic locus. Heterochromatin formation is influenced by the position of genomic integration of a transgene ("position effects" (Boivin and Dura, 1998)). Transgene integration occurs more or less at random. Since most of the genome is heterochromatin, most transgene loci are prone to silencing due to position effects.

[0010]A second transgene-silencing phenomenon can occur when two or more copies of a transgene are integrated into a genome during construction of a recombinant cell line. Formation of tandem transgene repeats often occurs during the initial integration step. Furthermore, in order to increase product yield, many recombinant host cell lines are engineered after the integration step to amplify the copy number of a transgene, which also results in tandem transgene repeats (Kaufman, 1990). Tandem repeats and other configurations of multiple transgene copies are particularly prone to silencing ("repeat-induced gene silencing" (Garrick et al., 1998)).

[0011]In case that a genome contains multiple copies of a transgene, the yield can also decline via another phenomenon than transcriptional silencing. The number of copies of the transgene can decline during cultivation of a recombinant host cell line. The productivity of such cell lines at the time of selection for use is correlated with a transgene copy number, and consequently as copies of a transgene are lost, the yield declines (Kaufman, 1990).

[0012](c) Different cell types in a mammalian organism have different capacities for post-translational modification and secretion of proteins. The functions of some cell types include production of large quantities of secreted proteins; examples include lymphocytes (producing immunoglobulins), hepatocytes (producing serum proteins), and fibroblasts (producing extracellular matrix proteins). These cell types are favorable sources for deriving host cell lines for production of secreted heterologous proteins. More favorable is the use of a cell line whose progenitor organismal cell type secretes a protein or class of proteins of interest. For example, it is particularly favorable to express recombinant monoclonal antibodies in lymphocytes (or host cells derived from lymphocytes), erythropoietin in hepatocytes (or host cells derived from hepatocytes), and blood clotting factors (e.g., Factor VIII and van Willebrand's factor) in endothelial cells (or host cells derived from endothelial cells).

[0013]The use of specific cell types (or cell lines derived therefrom) for production of their affiliated proteins is favorable because such specific cell types will carry out proper post-translational modifications of produced proteins. However, specific cell types often do not have high secretory capacities. For example, cells of the central nervous system, such as neurons, have low intrinsic protein secretion capacities. These cells do secrete proteins, however, including neurotrophins. Neurotrophins regulate the fate and shape of neuronal cells during fetal and juvenile development. Moreover, they influence patterns of neuronal degeneration and regeneration in adults (Bibel and Barde, 2000). Production of neurotrophins for therapeutic applications has considerable biopharmaceutical value (e.g., Axokine®, recombinant cilliary neurotrophic factor from Regeneron). In order to produce heterologous neurotrophins with post-translational modifications (and hence functional properties) that match the naturally-occurring proteins, expression in host cells derived from the central nervous system is favorable. However, production of polypeptides such as neurotrophins in host cell lines such as those derived from neural tissue is inefficient using conventional methods. The predictability of identifying high-expressor isolates from these types of cell lines is often poor; the yield of proteins from such cell lines is generally low, and production levels are characteristically unstable.

[0014]Another drawback to a use of specific host cells for production of affiliated proteins is that it is usually difficult to isolate cell lines with favorable biotechnological characteristics. These characteristics for instance include the mode and rate of growth, and the ease of introduction of a transgene. Consequently, various general host cell lines have been established. Examples of these include CHO cells from Chinese hamster ovary (ATCC (American Type Culture Collection) CCL-61), BHK cells from baby hamster kidney (ATCC CCL-10), and Vero cells from African green monkey kidney (ATCC CCL-81). These "general purpose" host cell lines are widely used for production of a number of heterologous proteins. A disadvantage of general purpose cell lines is that the post-translational modifications of heterologous proteins produced by them often differ from the post-translational modifications of the naturally occurring proteins. These differences can have functional consequences resulting in side effects, as discussed above.

[0015]Table 1 lists a number of proteins that are currently in use or under development for biopharmaceutical applications. It also lists the tissue or cell type in which each protein is normally produced in the human body. These 24 proteins (or protein classes) come from a wide range of cells and tissue, ranging from highly secretory cells (hepatocytes, endothelial cells) to cells with low secretory capacity (e.g., neural tissue). Currently, neither general-purpose host cells nor specific host cells have qualities that enable optimal expression of the broad spectrum of biopharmaceutically important secreted proteins.

[0016]Hence, protein production by conventional host cell lines involves a lot of disadvantages and complications, for instance with respect to yield and post-translational modifications. There is a need in the art for improved protein production in recombinant host cell lines.

SUMMARY OF THE INVENTION

[0017]The invention provides a method for producing a proteinaceous molecule in a cell comprising selecting a cell for its suitability for producing the proteinaceous molecule, providing a nucleic acid encoding the proteinaceous molecule with a nucleic acid comprising a STAR (STabilizing Anti-Repression) sequence, expressing the resulting nucleic acid in the cell and collecting the proteinaceous molecule.

[0018]The STAR sequence has to be operably linked to the nucleic acid encoding the proteinaceous molecule in order to be effective. In one embodiment of the invention, one STAR element is used. Preferably however, more than one STAR element is used. In a particularly preferred embodiment, the nucleic acid encoding the proteinaceous molecule is provided with two STAR sequences; one STAR sequence at the 5' side of the coding sequence of the nucleic acid and one STAR sequence at the 3' side of the coding sequence of the nucleic acid.

Description of STAR Elements

[0019]New transcription regulatory elements were disclosed by the present inventors, which are named STAR sequences (See EP 01202581.3). STAR sequences are nucleic acid sequences that comprise a capacity to influence transcription of genes in cis. Typically, although not necessarily, the STAR sequences do not code by themselves for a functional protein.

[0020]A STAR sequence has a gene transcription modulating quality in at least one type of cell. A STAR sequence is capable of enhancing gene transcription resulting in a higher yield, increasing the proportion of transgene-comprising host cells with acceptable expression levels, and/or increasing stability of transgenes in recombinant cell lines.

[0021]In EP 01202581.3 a method of detecting, and optionally selecting, a STAR sequence is provided, comprising providing a transcription system with a variety of a fragment-comprising vectors, the vectors comprising i) an element with a gene-transcription repressing quality, and ii) a promoter directing transcription of a reporter gene, the method further comprising performing a selection step in the transcription system in order to identify the STAR sequence. In a preferred embodiment, the fragments are located between i) the element with a gene-transcription repressing quality, and ii) the promoter directing transcription of the reporter gene. RNA polymerase initiates the transcription process after binding to a specific sequence, called the promoter, that signals where RNA synthesis should begin. A STAR sequence can enhance transcription from the promoter in cis, in a given cell type and/or a given promoter.

[0022]Methods disclosed in EP 01202581.3 have been used to isolate STAR elements from the human genome. Isolated human STAR elements have been placed in DNA vectors so as to flank transgene expression units, and the vectors have subsequently been integrated into host cell genomes. Transgene expression in these recombinant host cells has been compared to expression in similar host cells in which the expression units are not flanked by STAR elements. The results show that STAR elements have at least one of three consequences for production of (heterologous) proteinaceous molecule (also referred to as (heterologous) protein): (1) they increase the predictability of identifying host cell lines that express a proteinaceous molecule at industrially acceptable levels; (2) they result in host cell lines with increased protein yields; and/or (3) they result in host cell lines that exhibit more stable protein production during prolonged cultivation. Each of these attributes is discussed in more detail below:

[0023](1) Increased predictability: Integration of transgene expression units can occur at random positions throughout the host cell genome. However, much of the genome is transcriptionally silent heterochromatin. When the expression units include STAR elements flanking the transgene, the position of integration has a reduced effect on expression. The STAR elements impair the ability of adjacent heterochromatin to silence the transgene. Consequently, the proportion of transgene-containing host cells with acceptable expression levels is increased.

[0024](2) Yield: The levels of protein expression in primary populations of recombinant host cells, directly after transgene integration, have been surveyed. The expression level of individuals in the populations varies. However, when the transgenes are protected by STAR elements, the variability is reduced. This reduced variability is most conspicuous in that fewer clones are recovered that have low levels of expression. Furthermore, the populations with STAR elements commonly have individuals with strikingly high expression. These high-yielding individuals are favorable for production of proteinaceous molecules.

[0025](3) Increased stability: STAR elements increase the stability of transgenes in recombinant host cell lines by ensuring that the transgenes are not transcriptionally silenced during prolonged cultivation. Comparative trials show that, under conditions in which transgenes that are not protected by STAR elements are progressively silenced (5 to 25 passages in cultivation), STAR element-protected transgenes continue to be expressed at high levels. This is an advantage during industrial production of proteinaceous molecules, during which cell cultivation continues for prolonged periods, from a few weeks to many months.

[0026]Hence, a STAR sequence can enhance expression of a heterologous proteinaceous molecule. In addition, a STAR sequence can enhance expression of a naturally produced proteinaceous molecule.

[0027]Transcription can be influenced through a direct effect of the STAR sequence (or the protein(s) binding to it) on the transcription of a particular promoter. Transcription can however, also be influenced by an indirect effect, for instance because the STAR sequence affects the function of one or more other regulatory elements. A STAR sequence can also comprise a stable gene transcription quality. Frequently, expression levels drop dramatically with increasing numbers of cell divisions. With the methods disclosed in EP 01202581.3 it is possible to detect and optionally select a DNA sequence that is capable of at least in part preventing the dramatic drop in transcription levels with increasing numbers of cell divisions. Strikingly, fragments comprising a STAR sequence can be detected and optionally selected with a method EP 01202581.3, in spite of the fact that the method does not necessarily measure long term stability of transcription.

[0028]A STAR sequence is suitable for enhancing the level of transcription of a gene of interest in a host cell. If, together with a gene of interest, a STAR sequence is also introduced into host cells, more clones can be detected that express more than a certain amount of the gene of interest. As used herein, such host cells are termed "host cells with acceptable expression levels."

[0029]Furthermore, if, together with a gene of interest, a STAR sequence is also introduced into host cells, a higher yield of produced proteinaceous molecules can be obtained, while gene expression level is also more stable than in the absence of such STAR sequences. Preferably, a STAR sequence derived from a plant and/or vertebrate is used. More preferably a human STAR sequence is used.

[0030]Sequences comprising a STAR sequence can be found by using a functional assay, as described above. However, once a collection of such sequences has been identified, bioinformatics can be used to find other STAR sequences. Several methods are available in the art to extract sequence identifiers from a family of DNA sequences sharing a certain common feature. Such sequence identifiers can subsequently be used to identify sequences that share one or more identifiers. Sequences sharing such one or more identifiers are likely to be a member of the same family of sequences, i.e., are likely to share the common feature of the family. By the present inventors a large number of sequences comprising STAR activity (so-called STAR sequences) were used to obtain sequence identifiers (patterns) which are characteristic for sequences comprising STAR activity. These patterns can be used to determine whether a test sequence is likely to contain STAR activity. A method for detecting the presence of a STAR sequence within a nucleic acid sequence of about 50-5000 base pairs is thus provided, comprising determining the frequency of occurrence in the sequence of at least one sequence pattern and determining that the frequency of occurrence is representative of the frequency of occurrence of at least one sequence pattern in at least one sequence comprising a STAR sequence. In principle any method is suited for determining whether a sequence pattern is representative of a STAR sequence. Many different methods are available in the art. Preferably, the step of determining that the occurrence is representative of the frequency of occurrence of at least one sequence pattern in at least one sequence comprising a STAR sequence comprises, determining that the frequency of occurrence of at least one sequence pattern significantly differs between at least one STAR sequence and at least one control sequence. In principle any significant difference is discriminative for the presence of a STAR sequence. However, in a particularly preferred embodiment, the frequency of occurrence of at least one sequence pattern is significantly higher in at least one sequence comprising a STAR sequence compared to at least one control sequence.

[0031]A considerable number of sequences comprising a STAR sequence have been identified by the present inventors. It is possible to use these sequences to test how efficient a pattern is in discriminating between a control sequence and a sequence comprising a STAR sequence. Using so-called discriminant analysis it is possible to determine on the basis of any set of STAR sequences in a species, the most optimal discriminative sequence patterns or combination thereof. Thus, preferably, at least one of the patterns is selected on the basis of optimal discrimination between at least one sequence comprising a STAR sequence and a control sequence.

[0032]In a preferred embodiment, the frequency of occurrence of a sequence pattern in a test nucleic acid is compared with the frequency of occurrence in a sequence known to contain a STAR sequence. In this case, a pattern is considered representative for a sequence comprising a STAR sequence if the frequencies of occurrence are similar. In a preferred embodiment, another criterion is used. The frequency of occurrence of a pattern in a sequence comprising a STAR sequence is compared to the frequency of occurrence of the pattern in a control sequence. By comparing the two frequencies it is possible to determine for each pattern thus analyzed, whether the frequency in the sequence comprising the STAR sequence is significantly different from the frequency in the control sequence. In this embodiment, a sequence pattern is considered to be representative of a sequence comprising a STAR sequence, if the frequency of occurrence of the pattern in at least one sequence comprising a STAR sequence is significantly different from the frequency of occurrence of the same pattern in a control sequence. By using larger numbers of sequences comprising a STAR sequence the number of patterns for which a statistical difference can be established increases, thus enlarging the number of patterns for which the frequency of occurrence is representative for a sequence comprising a STAR sequence. Preferably, the frequency of occurrence is representative of the frequency of occurrence of at least one sequence pattern in at least two sequences comprising a STAR sequence; more preferably, in at least five sequences comprising a STAR sequence; and, even more preferably, in at least ten sequences comprising a STAR sequence. More preferably, the frequency of occurrence is representative of the frequency of occurrence of at least one sequence pattern in at least 20 sequences comprising a STAR sequence. In a particularly preferred embodiment, the frequency of occurrence is representative of the frequency of occurrence of at least one sequence pattern in at least 50 sequences comprising a STAR.

[0033]The patterns that are indicative for a sequence comprising a STAR sequence are also dependent on the type of control nucleic acid used. The type of control sequence used is preferably selected on the basis of the sequence in which the presence of a STAR sequence is to be detected. In a preferred embodiment, the control sequence comprises a random sequence comprising a similar AT/CG content as at least one sequence comprising a STAR sequence. In another preferred embodiment, the control sequence is derived from the same species as the sequence comprising the STAR sequence. For instance, if a test sequence is scrutinized for the presence of a STAR sequence, active in a plant cell, then preferably the control sequence is also derived from a plant cell. Similarly, for testing for STAR activity in a human cell, the control nucleic acid is preferably also derived from a human genome. In a preferred embodiment, the control sequence comprises between 50% and 150% of the bases of at least one sequence comprising a STAR sequence. In a particularly preferred embodiment, the control sequence comprises between 90% and 110% of the bases of at least one sequence comprising a STAR sequence. More preferably, between 95% and 105%.

[0034]A pattern can comprise any number of bases larger than two. Preferably, at least one sequence pattern comprises at least five, more preferably at least six, bases. In another embodiment, at least one sequence pattern comprises at least eight bases. In a preferred embodiment, the at least one sequence pattern comprises a pattern listed in Table 6 and/or Table 7. A pattern may consist of a consecutive list of bases. However, the pattern may also comprise bases that are interrupted one or more times by a number of bases that are not or only partly discriminative. A partly discriminative base is, for instance, indicated as a purine.

[0035]Preferably, the presence of STAR activity is verified using a functional assay. Several methods are presented herein to determine whether a sequence comprises STAR activity. STAR activity is confirmed if the sequence is capable of performing at least one of the following functions: (i) at least in part inhibiting the effect of sequence comprising a gene transcription repressing element of the invention, (ii) at least in part blocking chromatin-associated repression, (iii) at least in part blocking activity of an enhancer, (iv) conferring upon an operably linked nucleic acid encoding a transcription unit compared to the same nucleic acid alone, (iv-a) a higher predictability of transcription, (iv-b) a higher transcription, and/or (iv-c) a higher stability of transcription over time.

[0036]The large number of sequences comprising STAR activity identified by the present inventors open up a wide variety of possibilities to generate and identify sequences comprising the same activity in kind not necessarily in amount. For instance, it is well within the reach of a skilled person to alter the sequences identified in the invention and test the altered sequence for STAR activity. Such altered sequences are, therefore, also part of the invention. Alteration can include deletion, insertion and mutation of one or more bases in the sequences.

[0037]Sequences comprising STAR activity were identified in stretches of 400 bases. However, it is expected that not all of these 400 bases are required to retain STAR activity. Methods to delimit the sequences that confer a certain property to a fragment of between 400 and 5000 bases are well known. The minimal sequence length of a fragment comprising STAR activity is estimated to be about 50 bases.

[0038]Table 6 (SEQ ID NOS:177-342) and Table 7 (SEQ ID NOS:343-1072) list patterns of six bases that have been found to be over represented in nucleic acid molecules comprising STAR activity. This over representation is considered to be representative for a STAR sequence. The tables were generated for a family of 65 STAR sequences (SEQ ID NOS:1-65). Similar tables can be generated starting from a different set of STAR sequences, or from a smaller or larger set of STAR sequences. A pattern is representative for a STAR sequence if it is over represented in the STAR sequence compared to a sequence not comprising a STAR element. This can be a random sequence. However, to exclude a non relevant bias, the sequence comprising a STAR sequence is preferably compared to a genome or a significant part thereof. Preferably, a genome of a vertebrate or plant, more preferably, a human genome. A significant part of a genome is, for instance, a chromosome. Preferably the sequence comprising a STAR sequence and the control sequence are derived from nucleic acid of the same species.

[0039]The more STAR sequences are used for the determination of the frequency of occurrence of sequence patterns, the more representative for STARs the patterns are that are over- or under-represented. Considering that many of the functional features that can be expressed by nucleic acids are mediated by proteinaceous molecules binding to them, it is preferred that the representative pattern is over-represented in the STAR sequences. Such over-represented pattern can be part of a binding site for such a proteinaceous molecule. Preferably, the frequency of occurrence is representative of the frequency of occurrence of at least one sequence pattern in at least two sequences comprising a STAR sequence; more preferably, in at least five sequences comprising a STAR sequence; and, even more preferably, in at least ten sequences comprising a STAR sequence. More preferably, the frequency of occurrence is representative of the frequency of occurrence of at least one sequence pattern in at least 20 sequences comprising a STAR sequence. In a particularly preferred embodiment, the frequency of occurrence is representative of the frequency of occurrence of at least one sequence pattern in at least 50 sequences comprising a STAR. Preferably, the sequences comprising a STAR sequence comprises at least one of the sequences depicted in the sequences comprising STAR1-STAR65 (SEQ ID NOS:1-65), sequences comprising STAR66 and testing set (SEQ ID NOS:66-84), and sequences comprising Arabidopsis STAR A1-A35 (SEQ ID NOS:85-119) (hereinafter SEQ ID NOS:1-119).

[0040]STAR activity is a feature shared by the sequences listed in SEQ ID NOS:1-119. However, this does not mean that they must all share the same identifier sequence. It is very well possible that different identifiers exist. Identifiers may confer this common feature onto a fragment containing it, though this is not necessarily so.

[0041]By using more sequences comprising STAR activity for determining the frequency of occurrence of a sequence pattern or patterns, it is possible to select patterns that are more often than others present or absent in such a STAR sequence. In this way it is possible to find patterns that are very frequently over- or under-represented in STAR sequences. Frequently, over- or under-represented patterns are more likely to identify candidate STAR sequences in test sets. Another way of using a set of over- or under-represented patterns is to determine which pattern or combination of patterns is best suited to identify a STAR in a sequence. Using so-called discriminative statistics, we have identified a set of patterns that performs best in identifying a sequence comprising a STAR element. In a preferred embodiment, at least one of the sequence patterns for detecting a STAR sequence comprises a sequence pattern GGACCC (SEQ ID NO:464), CCCTGC (SEQ ID NO:816), AAGCCC (SEQ ID NO:270), CCCCCA (SEQ ID NO:298) and/or AGCACC (SEQ ID NO:336). In another embodiment, at least one of the sequence patterns for detecting a STAR sequence comprises a sequence pattern CCCN{16}AGC (SEQ ID NO:415), GGCN{9}GAC (SEQ ID NO:536), CACN{13}AGG (SEQ ID NO:761), and/or CTGN{4}GCC (SEQ ID NO:839).

[0042]A list of STAR sequences can also be used to determine one or more consensus sequences therein. The invention, therefore, also provides a consensus sequence for a STAR element. This consensus sequence can of course be used to identify candidate STAR elements in a test sequence.

[0043]Moreover, once a sequence comprising a STAR element has been identified in a vertebrate it can be used by means of sequence homology to identify sequences comprising a STAR element in other species belonging to vertebrate. Preferably a mammalian STAR sequence is used to screen for STAR sequences in other mammalian species. Similarly, once a STAR sequence has been identified in a plant species, it can be used to screen for homologous sequences with similar function in other plant species. The invention in one aspect provides a STAR sequence obtainable by a method according to the invention. Further provided is a collection of STAR sequences. Preferably, the STAR sequence is a vertebrate or plant STAR sequence. More preferably, the STAR sequence is a mammalian STAR sequence or an angiosperm (monocot, such as rice or dicot, such as Arabidopsis). More preferably, the STAR sequence is a primate and/or human STAR sequence.

[0044]A list of sequences comprising STAR activity can be used to determine whether a test sequence comprises a STAR element. There are, as mentioned above, many different methods for using such a list for this purpose. In a preferred embodiment, the invention provides a method for determining whether a nucleic acid sequence of about 50-5000 base pairs comprises a STAR sequence, the method comprising: generating a first table of sequence patterns comprising the frequency of occurrence of the patterns in a collection of STAR sequences of the invention; generating a second table of the patterns comprising the frequency of occurrence of the patterns in at least one reference sequence; selecting at least one pattern of which the frequency of occurrence differs between the two tables; determining, within the nucleic acid sequence of about 50-5000 base pairs, the frequency of occurrence of at least one of the selected patterns; and determining whether the occurrence in the test nucleic acid is representative of the occurrence of the selected pattern in the collection of STAR sequences. Alternatively, determining comprises determining whether the frequency of occurrence in the test nucleic acid is representative of the frequency occurrence of the selected pattern in the collection of STAR sequences. Preferably, the method further comprises determining whether the candidate STAR comprises a gene transcription modulating quality using a method of the invention. Preferably, the collection of STARS comprises sequence as depicted in SEQ ID NOS:1-119. In another aspect, the invention provides an isolated and/or recombinant nucleic acid sequence comprising a STAR sequence obtainable by a method of the invention.

[0045]As mentioned above, a STAR sequence can exert its activity in a directional way, i.e., more to one side of the fragment containing it than to the other. Moreover, STAR activity can be amplified in amount by multiplying the number of STAR elements. The latter suggests that a STAR element may comprise one or more elements comprising STAR activity. Another way of identifying a sequence capable of conferring STAR activity on a fragment containing it comprises selecting from a vertebrate or plant sequence, a sequence comprising STAR activity and identifying whether the selected sequence and sequences flanking the selected sequence are conserved in another species. Such conserved flanking sequences are likely to be functional sequences. In one aspect, the invention, therefore, provides a method for identifying a sequence comprising a STAR element comprising selecting a sequence of about 50 to 5000 base pairs from a vertebrate or plant species comprising a STAR element and identifying whether sequences flanking the selected sequence in the species are conserved in at least one other species. The invention, therefore, further provides a method for detecting the presence of a STAR sequence within a nucleic acid sequence of about 50-5000 base pairs, comprising identifying a sequence comprising a STAR sequence in a part of a chromosome of a cell of a species and detecting significant homology between the sequence and a sequence of a chromosome of a different species. Preferably, the species comprises a plant or vertebrate species, ideally a mammalian species. The invention also provides a method for detecting the presence of a STAR element within a nucleic acid sequence of about 50-5000 base pairs of a vertebrate or plant species, comprising identifying whether a flanking sequence of the nucleic acid sequence is conserved in at least one other species.

[0046]It is important to note that methods of the invention for detecting the presence of a sequence comprising a STAR sequence using bioinformatical information are iterative in nature. The more sequences comprising a STAR sequence are identified with a method of the invention, the more patterns are found to be discriminative between a sequence comprising a STAR sequence and a control sequence. Using these newly found discriminative patterns, more sequences comprising a STAR sequence can be identified, which, in turn, enlarges the set of patterns that can discriminate and so on. This iterative aspect is an important aspect of methods provided in the invention.

BRIEF DESCRIPTION OF THE DRAWINGS

[0047]FIG. 1 is a diagram illustrating the pSelect plasmid used for isolating STAR elements. The zeocin resistance gene is under control of the SV40 promoter, and is upstream of the SV40 polyadenylation site. Upstream of the SV40 promoter is a tandem array of lexA operator sites. Between the lexA operators and the SV40 promoter is a cloning site; test DNAs (e.g., size-fractionated genomic DNA) are cloned into the BamHI site. The plasmid also has the hygromycin resistance gene (hygro) for selection of transformed cells, the EBNA-1 and oriP sequences for plasmid replication in mammalian cells, and the ampicillin resistance gene (ampR) and ori sequence for propagation in Escherichia coli.

[0048]FIG. 2 is a diagram depicting the pSDH-CSP plasmid used for testing STAR activity. The Secreted Alkaline Phosphatase (SEAP) reporter gene is under control of the CMV promoter, and the puromycin resistance selectable marker (puro) is under control of the SV40 promoter. Flanking these two genes are multiple cloning sites (MCSI and MCSII) into which STAR elements can be cloned. The plasmid also has an origin of replication (ori) and ampicillin resistance gene (amp^R) for propagation in Escherichia coli.

[0049]FIG. 3 is a graph showing that STAR6 (SEQ ID NO:6) and STAR8 (SEQ ID NO:8) improve predictability and yield of transgene expression in U-2 OS cells. Expression of luciferase from the CMV promoter by U-2 OS cells transfected with pSDH-CMV, pSDH-CMV-STAR6, or pSDH-CMV-STAR8 was determined. The STAR-containing constructs confer greater predictability and elevated yield relative to the pSDH-CMV construct alone.

[0050]FIG. 4 is a graph illustrating that STAR6 (SEQ ID NO:6), but not STAR8 (SEQ ID NO:8), improves predictability and yield of transgene expression in CHO cells. Expression of SEAP from the CMV promoter by CHO cells transfected with pSDH-CSP, pSDH-CSP-STAR6, or pSDH-CSP-STAR8 was determined. The STAR6-containing constructs confer greater predictability and elevated yield relative to the pSDH-CSP construct alone, identifying STAR6 (SEQ ID NO:6) as a promiscuous STAR element. In contrast, the STAR8-containing constructs do not consistently increase yield or predictability relative to the pSDH-CSP construct, suggesting that STAR8 (SEQ ID NO:8) is a cell line-specific STAR element.

[0051]FIG. 5 is a graph depicting that STAR6 (SEQ ID NO:6) and STAR49 (SEQ ID NO:49) improve predictability and yield of transgene expression. Expression of SEAP from the CMV promoter by CHO cells transfected with pSDH-CSP, pSDH-CSP-STAR6, or pSDH-CSP-STAR49 was determined. The STAR-containing constructs confer greater predictability and elevated yield relative to the pSDH-CSP construct alone.

[0052]FIG. 6 is a graph showing the minimal essential sequences of STAR10 (SEQ ID NO:10) and STAR27 (SEQ ID NO:27). Portions of the STAR elements were amplified by PCR: STAR10 (SEQ ID NO:10) was amplified with primers E23 (SEQ ID NO:166) and E12 (SEQ ID NO:155) to yield fragment 10A (corresponding approximately to the first 400 nucleotides of SEQ ID NO:10), E13 (SEQ ID NO:156) and E14 (SEQ ID NO:157) to yield fragment 10B (corresponding approximately to the second 400 nucleotides of SEQ ID NO:10), and E15 (SEQ ID NO:158) and E16 (SEQ ID NO:159) to yield fragment 10C (corresponding approximately to the third 400 nucleotides of SEQ ID NO:10). STAR27 (SEQ ID NO:27) was amplified with primers E17 (SEQ ID NO:160) and E18 (SEQ ID NO:161) to yield fragment 27A (corresponding approximately to the first 500 nucleotides of SEQ ID NO:27), E19 (SEQ ID NO:162) and E20 (SEQ ID NO:163) to yield fragment 27B (corresponding to the second 500 nucleotides of SEQ ID NO:27), and E21 (SEQ ID NO:164) and E22 (SEQ ID NO:165) to yield fragment 27C (corresponding approximately to the third 500 nucleotides of SEQ ID NO:27). These sub-fragments were cloned into the pSelect vector. After transfection into U-2 OS/Tet-Off/LexA-HP1 cells, the growth of the cultures in the presence of zeocin was monitored. Growth rates varied from vigorous (+++) to poor (+/-), while some cultures failed to survive zeocin treatment (-) due to absence of STAR activity in the DNA fragment tested.

[0053]FIG. 7 is a graph illustrating the STAR element function in the context of the SV40 promoter. pSDH-SV40 and pSDH-SV40-STAR6 were transfected into the human osteosarcoma U-2 OS cell line, and expression of luciferase was assayed with or without protection from gene silencing by STAR6 (SEQ ID NO:6) in puromycin-resistant clones.

[0054]FIG. 8 is a graph showing the STAR element function in the context of the Tet-Off promoter. pSDH-Tet and pSDH-Tet-STAR6 were transfected into the human osteosarcoma U-2 OS cell line, and expression of luciferase was assayed with or without protection from gene silencing by STAR6 (SEQ ID NO:6) in puromycin-resistant clones.

[0055]FIG. 9 is a schematic diagram of the orientation of STAR elements as they are cloned in the pSelect vector (panel A), as they are cloned into pSDH vectors to preserve their native orientation (panel B), and as they are cloned into pSDH vector in the opposite orientation (panel C).

[0056]FIG. 10 is a graph showing directionality of STAR66 (SEQ ID NO:66) function. The STAR66 (SEQ ID NO:66) element was cloned into pSDH-Tet in either the native (STAR66 native) or the opposite orientation (STAR66 opposite) and transfected into U-2 OS cells. Luciferase activity was assayed in puromycin resistant clones.

[0057]FIG. 11 is a southern blot showing copy number-dependence of STAR function. Southern blot of luciferase expression units in pSDH-Tet-STAR10, integrated into U-2 OS genomic DNA. Radioactive luciferase DNA probe was used to detect the amount of transgene DNA in the genome of each clone, which was then quantified with a phosphorimager.

[0058]FIG. 12 is a graph illustrating copy number-dependence of STAR function. The copy number of pSDH-Tet-STAR10 expression units in each clone was determined by phosphorimagery and compared with the activity of the luciferase reporter enzyme expressed by each clone.

[0059]FIG. 13 is a schematic diagram and graphs depicting enhancer-blocking and enhancer assays. The luciferase expression vectors used for testing STARs for enhancer-blocking and enhancer activity are shown schematically. The E-box binding site for the E47 enhancer protein is upstream of a cloning site for STAR elements. Downstream of the STAR cloning site is the luciferase gene under control of a human alkaline phosphatase minimal promoter (mp). The histograms indicate the expected outcomes for the three possible experimental situations (see text). Panel A: Enhancer-blocking assay. Panel B: Enhancer assay.

[0060]FIG. 14 is a graph showing enhancer-blocking assay. Luciferase expression from a minimal promoter is activated by the E47/E-box enhancer in the empty vector (vector). Insertion of enhancer-blockers (scs, HS4) or STAR elements (STAR elements 1, 2, 3, 6, 10, 11, 18, and 27; SEQ ID NOS:1, 2, 3, 6, 10, 11, 18 and 27, respectively) block luciferase activation by the E47/E-box enhancer.

[0061]FIG. 15 is a graph illustrating enhancer assay. Luciferase expression from a minimal promoter is activated by the E47/E-box enhancer in the empty vector (E47). Insertion of the scs and HS4 elements or various STAR elements (STARs 1, 2, 3, 6, 10, 11, 18, and 27; SEQ ID NOS:1, 2, 3, 6, 10, 11, 18 and 27, respectively) do not activate transcription of the reporter gene.

[0062]FIG. 16 illustrates STAR18 (SEQ ID NO:18) sequence conservation between mouse and human. The region of the human genome containing 497 base pair STAR18 (SEQ ID NO:18) is shown (black boxes); the element occurs between the HOXD8 and HOXD4 homeobox genes on human chromosome 2. It is aligned with a region in mouse chromosome 2 that shares 72% sequence identity. The region of human chromosome 2 immediately to the left of STAR18 (SEQ ID NO:18) is also highly conserved with mouse chromosome 2 (73% identity; gray boxes); beyond these region, the identity drops below 60%. The ability of these regions from human and mouse, either separately or in combination, to confer growth on zeocin is indicated: -, no growth; +, moderate growth; ++, vigorous growth; +++, rapid growth.

[0063]FIG. 17 is a schematic diagram of bio-informatic analysis workflow. For details, see text.

[0064]FIG. 18 is a schematic diagram showing the results of discriminant analysis on classification of the training set of 65 STAR elements. STAR elements that are correctly classified as STARs by Stepwise Linear Discriminant Analysis (LDA) are shown in a Venn diagram. The variables for LDA were selected from frequency analysis results for hexameric oligonucleotides ("oligos") and for dyads. The diagram indicates the concordance of the two sets of variables in correctly classifying STARs.

[0065]FIG. 19 is a graph illustrating that U-2 OS/Tet-Off/lexA-HP1 cells were transfected with candidate Arabidopsis STAR elements and cultivated at low doxycycline concentrations. Total RNA was isolated and subjected to RT-PCR; the bands corresponding to the zeocin and hygromycin resistance mRNAs were detected by Southern blotting and quantified with a phosphorimager. The ratio of the zeocin to hygromycin signals is shown for transfectants containing zeocin expression units flanked by 12 different Arabidopsis STAR elements, the Drosophila scs element, or no flanking element.

[0066]FIG. 20 is a schematic diagram and graph illustrating that STAR elements improve GFP expression in CHO cells. The ppGIZ and ppGIZ-STAR7 plasmids used for testing STAR activity are shown. The expression unit comprises (from 5' to 3') a transgene (encoding for the GFP protein), an IRES, and a selectable marker (zeo, conferring zeocin resistance) under control of the CMV promoter. The expression unit has the SV40 transcriptional terminator at its 3' end (t). The entire cassette with the expression unit is either flanked by STAR7 (SEQ ID NO:7) elements (STAR7-shielded) or not (Control). The constructs are transfected to CHO-K1 cells. Stable colonies are expanded and the GFP signal is determined on a XL-MCL Beckman Coulter flow cytometer. For each independent colony the mean of the GFP signal is plotted. This is taken as measure for the level of GFP expression. The results in FIG. 20 show that in CHO cells the STAR7-shielded construct confers greater predictability and elevated GFP expression relative to the ppGIZ control construct alone.

[0067]FIG. 21 is a schematic diagram and graph showing that STAR elements improve GFP expression in NSO cells. The ppGIZ and ppGIZ-STAR7 plasmids used for testing STAR activity are shown as in FIG. 20. The constructs are transfected to NSO cells. Stable colonies are expanded and the GFP signal is determined on a XL-MCL Beckman Coulter flow cytometer. For each independent colony the mean of the GFP signal is plotted. This is taken as measure for the level of GFP expression. The results in FIG. 21 show that in NSO cells the STAR7-shielded (SEQ ID NO:7) construct confers greater predictability and elevated GFP expression relative to the ppGIZ control construct alone.

[0068]FIG. 22 is a schematic diagram and graph depicting that STAR elements improve GFP expression in 293 cells. The ppGIZ and ppGIZ-STAR7 plasmids used for testing STAR activity are shown as in FIG. 20. The constructs are transfected to 293 cells. Stable colonies are expanded and the GFP signal is determined on a XL-MCL Beckman Coulter flow cytometer. For each independent colony, the mean of the GFP signal is plotted. This is taken as measure for the level of GFP expression. The results in FIG. 22 show that in 293 cells the STAR7-shielded (SEQ ID NO:7) construct confers greater predictability and elevated GFP expression relative to the ppGIZ control construct alone.

DETAILED DESCRIPTION OF THE INVENTION

Definitions

Quality

[0069]The term "quality" in relation to a sequence refers to an activity of the sequence.

STAR and STAR Sequence

[0070]The terms "STAR," "STAR sequence" or "STAR element," as used herein, refer to a DNA sequence comprising one or more of the mentioned gene transcription modulating qualities.

DNA Sequence

[0071]The term "DNA sequence" as used herein, unless otherwise specified, does not refer to a listing of specific ordering of bases, but rather to a physical piece of DNA. A transcription quality with reference to a DNA sequence refers to an effect that the DNA sequence has on transcription of a gene of interest. "Quality" as used herein refers to detectable properties or attributes of a nucleic acid or protein in a transcription system.

Proteinaceous Molecule

[0072]By a "proteinaceous molecule" is meant herein a molecule comprising amino acids. At least a part of the amino acids are bound to each other to form a peptide. Preferably, the proteinaceous molecule comprises a polypeptide. In this application, the term "proteinaceous molecule" also includes "polypeptide."

Essentially the Same Properties

[0073]By "essentially the same properties" is meant that the properties are essentially the same in kind, not necessarily in amount. For instance, if a proteinaceous molecule has essentially the same properties as a pharmaceutically active compound, the proteinaceous molecule also displays such pharmaceutical activity in kind, not necessarily in amount.

Naturally Occurring Proteinaceous Molecule of the Same Kind

[0074]By a "naturally occurring proteinaceous molecule of the same kind" is meant a proteinaceous molecule with the same primary structure, which is naturally produced in vivo, not influenced by human interference. Examples comprise an antibody produced in vivo by a lymphocyte and erythropoietin produced in vivo by a hepatocyte.

Host Cell, Host Cell Line

[0075]As used herein, the terms "host cell" and "host cell line" refer to a cell and to homogeneous populations thereof that are capable of expressing a nucleic acid encoding a proteinaceous molecule.

Recombinant Host Cell, Recombinant Host Cell Line

[0076]The terms "recombinant host cell" and "recombinant host cell line" refer to a host cell and to homogeneous populations thereof into which a nucleic acid has been introduced.

Expression

[0077]As used herein, the term "expression" refers to production of a proteinaceous molecule, encoded by a nucleic acid. The production, for instance, involves transcription of a DNA sequence, translation of the corresponding mRNA sequence, and/or posttranslational modification. In case of secreted proteins, it can also refer to the processes of transcription, translation, and/or post-translational modification (e.g., glycosylation, disulfide bond formation, etc.), followed by exocytosis. In the case of multimeric proteins, it can include assembly of the multimeric structure from the polypeptide monomers.

Silencing

[0078]The term "silencing" refers to diminution of a level of expression of a gene or genes, including transgenes, typically over time. The expression level can be diminished but still detectable, or diminished below the threshold of detection.

Enhanced Expression

[0079]As used herein, "enhanced expression" of a gene encoding a proteinaceous molecule, or enhanced production of a proteinaceous molecule, can either involve a higher yield of the proteinaceous molecule, a higher proportion of host cells with acceptable expression levels, and/or a higher stability of a gene expression level.

Affiliated Proteinaceous Molecule of a Cell

[0080]By an "affiliated proteinaceous molecule of a cell" is meant a proteinaceous molecule which is naturally produced by the kind of cell in the organism from which the cell is derived.

[0081]For instance, erythropoietin is an affiliated proteinaceous molecule of a hepatocyte, or of a hepatocyte-derived cell line. Likewise, an antibody is an affiliated proteinaceous molecule of a lymphocyte, or of a lymphocyte-derived cell line, typically of a B-cell or a B-cell derived cell line.

Specific Host Cell Line

[0082]A "specific host cell line" is a host cell line derived from a cell which normally expresses a particular proteinaceous molecule (or class of proteinaceous molecules) in the organism from which the cell is derived.

Heterologous STAR Sequence

[0083]The term "heterologous STAR sequence" is herein used to define a STAR sequence that is, for example, obtained from a different cell type (from the same species or organism) or is obtained from a different species or organism (either from the same cell type or a different cell type) compared to the cell in which it is used.

Stable

[0084]Stable" means that the observed transcription level is not significantly changed over at least 30 cell divisions. A stable quality is useful in situations wherein expression characteristics should be predictable over many cell divisions. Typical examples are cell lines transfected with foreign genes. Other examples are transgenic animals and plants and gene therapies. Very often, introduced expression cassettes function differently after increasing numbers of cell divisions or plant or animal generations. A stable quality preferably comprises a capacity to maintain gene transcription in subsequent generations of a transgenic plant or animal. Of course, in the case where expression is inducible, the quality comprises the quality to maintain inducibility of expression in subsequent generations of a transgenic plant or animal.

Acceptable Expression Level

[0085]An "acceptable expression level" means an acceptable expression level for commercial exploitation. Whether or not a certain expression level is acceptable for commercial exploitation often depends on the kind of proteinaceous molecule that is produced. Acceptable expression levels of different kinds of proteinaceous molecules often involve different amounts of produced proteinaceous molecule.

[0086]A STAR sequence, a collection of STAR sequences, and/or a nucleic acid comprising a STAR sequence obtainable by a method of the invention, is of course suitable for use in a method of the invention for producing a proteinaceous molecule in a cell. In one aspect, the invention, therefore, provides a method for producing a proteinaceous molecule in a cell comprising selecting a cell for its suitability for producing the proteinaceous molecule, providing a nucleic acid encoding the proteinaceous molecule with a nucleic acid comprising a STAR sequence, expressing the resulting nucleic acid in the cell and collecting the proteinaceous molecule, wherein the nucleic acid comprising a STAR sequence is obtainable by a method of the invention for identifying and obtaining a nucleic acid comprising a STAR sequence. The nucleic acid comprising a STAR sequence can be identified and obtained using at least one pattern that is representative for sequences comprising STAR activity. Preferably, the nucleic acid comprising a STAR sequence is identified and obtained using at least one pattern as depicted in Table 6 (SEQ ID NOS:177-342) or Table 7 (SEQ ID NOS:343-1072).

[0087]A cell can be selected for its suitability for producing a proteinaceous molecule in many different ways. For instance, it can be determined whether the cell is competent of nucleic acid uptake. A nucleic acid encoding a proteinaceous molecule is preferably easily introduced into the cell. Furthermore it can be determined whether the cell secretes produced proteinaceous molecule. Secreted proteinaceous molecule can usually be easily collected. Collecting proteinaceous molecules that are not secreted usually involves sacrificing at least part of a culture. This implicates separating a proteinaceous molecule of interest from other cell components, optionally starting up a new culture, etc. This is more cumbersome. Hence, in a preferred embodiment, a method of the invention is provided wherein the proteinaceous molecule is secreted by the cell.

[0088]In another preferred embodiment, a method of the invention is provided wherein the cell is selected for its capability of post-translationally modifying the proteinaceous molecule, such that the proteinaceous molecule has essentially the same properties as a naturally occurring proteinaceous molecule of the same kind. As has been explained above, different kinds of cells display different post-translational modifications. As a result, the same proteinaceous molecule can be modified differently when produced in different host cells. These differences can affect the properties of such proteinaceous molecules, such as for instance pharmaceutical properties. It is, therefore, highly preferred to select a cell which produces a proteinaceous molecule with essentially the same properties as its naturally occurring counterpart. This does not necessarily mean that the host cell has to display exactly the same kind of post-translational modifications, as long as the produced proteinaceous molecule has essentially the same properties. A proteinaceous molecule can be produced that is physically different from its natural counterpart, but which is functionally essentially the same.

[0089]In one embodiment, of the invention, however, a cell is selected for its capability of post-translationally modifying the proteinaceous molecule in essentially the same way as the proteinaceous molecule is post-translationally modified in nature.

[0090]In one aspect, the invention provides a method of the invention wherein the proteinaceous molecule comprises an affiliated proteinaceous molecule of the cell.

[0091]It is especially preferred to choose a host cell, or a cell line derived from a cell, which normally produces a proteinaceous molecule of interest in the organism from which the cell is derived. These cells are capable of carrying out post-translational modifications of their affiliated proteinaceous molecules such that the resulting proteinaceous molecule has the same kind of properties in kind, not necessarily in amount, as a proteinaceous molecule of the same kind which is normally present in the organism. Such specific cells are naturally adapted for production of the affiliated proteinaceous molecule. Apart from other activities of STAR sequences it is also possible to at least partly solve a problem of low production of proteinaceous molecules, which often occurs with such specific cells. Providing at least one STAR sequence to a nucleic acid encoding such proteinaceous molecule will enhance production (yield) of the proteinaceous molecule by the specific cell, increase the proportion of host cells with acceptable expression levels, and/or increase stability of a gene expression level.

[0092]In another preferred embodiment, a method of the invention is disclosed wherein the cell is selected for suitable growth in a suspension culture. This facilitates culturing of the cell, and collection of produced proteinaceous molecule, especially when the proteinaceous molecule is secreted into the suspension. More preferably, the cell is selected for suitable growth in a serum-free culture, since serum can contain contaminants and pathogens. Such contaminants/pathogens often have to be separated from produced proteinaceous molecule. This requires an extra step, which consumes time and chemicals, with a potential loss of produced proteinaceous molecule. Moreover, a possibility of a presence of pathogens involves a potential risk for employees. If a pathogen has been present in a culture, a produced proteinaceous molecule is not allowed to be used anymore for commercial and/or medical applications.

[0093]In yet another preferred embodiment, the cell is selected for the presence of an adenovirus Early Region 1 (E1) sequence. The presence of an adenoviral E1 sequence enhances protein production in a cell. Hence, an adenoviral E1 sequence is suitable for host cells engineered for protein production.

[0094]The invention also provides a method for producing a proteinaceous molecule comprising: [0095]providing a host cell with a nucleic acid comprising a STAR sequence; [0096]selecting a cell with enhanced expression of a proteinaceous molecule; and [0097]collecting the proteinaceous molecule.

[0098]In one embodiment, the method is performed with a host cell whose genome has not been modified by human interference. The method then results in enhanced expression of a proteinaceous molecule which is encoded by the genome of the host cell. The proteinaceous molecule may be normally expressed by the host cell in the organism from which the cell is derived, but it may also normally be subject to silencing, resulting in little or no expression in the host cell under normal conditions. Introduction of at least one STAR sequence can at least in part inhibit silencing of a gene of interest induced by gene-transcription repressing chromatin. Expression of a proteinaceous molecule is enhanced by introduction of a STAR sequence.

[0099]In another embodiment, the host cell is transfected with a nucleic acid of interest. Such nucleic acid for instance, encodes a heterologous proteinaceous molecule which is not naturally encoded by the genome of the host cell. Introduction of a STAR sequence also enhances expression of such heterologous proteinaceous molecule.

[0100]The STAR sequence can be introduced randomly into the genome of the host cell, using methods known in the art (for instance calcium precipitation, transfection with a vector comprising a nucleic acid of interest, use of a gene delivery vehicle, etc). If a STAR sequence is introduced near a nucleic acid sequence encoding a proteinaceous molecule, it is capable of enhancing expression of the proteinaceous molecule. Cells expressing a desired proteinaceous molecule can be isolated from cultures with randomly inserted STAR sequences.

[0101]Preferably, the STAR sequence is introduced into the host cell by homologous recombination. A nucleic acid comprising a STAR sequence can be provided with an additional sequence. The additional sequence can be chosen such that it is at least in part homologous to a nucleic acid sequence in the host cell which is known to be present in vicinity of a gene encoding a proteinaceous molecule of interest. If a nucleic acid comprising a STAR sequence and such additional sequence is provided to the host cell, it can be incorporated into the host cell's genome by homologous recombination at the site with the (partly) homologous nucleic acid sequence. As a result, the STAR sequence is introduced in vicinity of the gene encoding the proteinaceous molecule of interest. Expression of the proteinaceous molecule is then enhanced by the introduced STAR sequence.

[0102]A preferred embodiment of the invention provides a method of the invention wherein the STAR sequence comprises a species-specific STAR sequence. More preferably, the STAR sequence comprises a cell type-specific STAR sequence.

[0103]Two types of STAR elements have been identified. Promiscuous STAR elements are able to function in more than one host cell line. For example, STAR6 (SEQ ID NO:6) increases the predictability, yield, and stability of a transgene in both the U-2 OS human osteosarcoma cell line and in CHO (Chinese hamster ovary) cells. Other STAR elements are species-specific and/or cell type-specific; for example, STAR8 (SEQ ID NO:8) increases the predictability, yield, and stability of transgenes in U-2 OS cells, but not in CHO cells (see Examples 2 and 3 and FIGS. 3 and 4).

[0104]If a certain type of host cell (line) is chosen for expression of a proteinaceous molecule (for instance, because it is known to possess a preferred post-translational modification system) a STAR sequence which is naturally present in the cell can be used in a method of the invention. Such STAR sequence is referred to as a cell type-specific STAR sequence. A STAR sequence which is naturally present in a species from which the cell is derived can also be used. Such STAR sequence is referred to as a species-specific STAR sequence. A species-specific STAR sequence may be naturally present in the cell type, although this is not necessary.

[0105]A known species-specific STAR sequence or cell-type specific STAR sequence can be used in a method of the invention. Alternatively, a (previously unknown) species-specific STAR sequence or cell-type specific STAR sequence can be detected and isolated by a method as described by the present inventors (EP 01202581.3). The use of a species-specific STAR sequence or cell type-specific STAR sequence is preferred because such sequence is especially active in the host cell and is adapted to the specific circumstances within the cell. For instance, such cell type-specific STAR sequence may interact with a protein which is not present in some other cell-types. In that case, the cell type-specific STAR sequence will be less capable--if at all--of enhancing expression in cells lacking the protein. A species-specific or cell type-specific STAR element often has functional characteristics that are superior to promiscuous STAR elements. Furthermore, a cell line-specific STAR element can satisfy product safety or ethical considerations for use of the host cell line.

[0106]A promiscuous STAR sequence is particularly useful if no tissue specific or cell-type specific STAR sequence is known. In that case a known promiscuous STAR sequence can be used. This saves efforts to detect and isolate a cell-type specific STAR sequence.

[0107]Several STAR sequences are listed in SEQ ID NOS:1-119. Hence, in one aspect, a method of the invention is provided wherein the STAR sequence comprises a sequence as depicted in SEQ ID NOS:1-119.

[0108]In a preferred embodiment, the invention provides a cell line that comprises at least one heterologous STAR sequence or a functional equivalent and/or a functional fragment thereof. In an even more preferred embodiment, the cell line is a human cell line. The invention provides multiple examples of STAR sequences and also methods of testing STAR sequences and hence, a person skilled in the art is very well capable of obtaining a functional equivalent and/or a functional fragment of a STAR sequence, for example by deletion or mutation. In yet another preferred embodiment, the invention provides a non-human cell line that comprises at least one recombinant STAR sequence derived or obtained from a human cell, i.e., a human STAR sequence. The amount of STAR sequences may vary, e.g., a cell line according to the invention may comprise two, three, or four, or even more STAR sequences which may either be identical or different from each other.

[0109]In one aspect, the invention provides a cell line provided with a nucleic acid comprising a STAR sequence, wherein the cell line is selected for its suitability for producing a proteinaceous molecule. Preferably, a cell line of the invention comprises a vertebrate or plant cell line. A vertebrate cell line is very suitable for producing a human proteinaceous molecule of interest, because vertebrates are phylogenetically close related.

[0110]Plant cells are for instance very suitable for vaccine production. Vaccine production in plants can be inexpensive, while the vaccine can be easily delivered to an individual by eating the edible portion of the plant (Mercenier et al., 2001).

[0111]A cell line of the invention is particularly suitable for production of a proteinaceous molecule of interest, because the STAR sequence can enhance expression of a gene of interest (higher yield of a proteinaceous molecule, higher proportion of host cells with acceptable expression levels, and/or higher stability of a gene expression level). Methods for generating a cell line are known in the art and many techniques are known to provide a cell with a nucleic acid of interest. Furthermore, many general purpose cell lines are available. Such cell lines can be dedicated to production of a certain proteinaceous molecule using recombinant techniques. Examples of available cell lines include CHO cells from Chinese hamster ovary and BHK cells from baby hamster kidney (as described above).

[0112]Another embodiment of the invention provides a cell line provided with a nucleic acid comprising a STAR sequence, wherein the cell line comprises an adenovirus Early Region 1 sequence. As has been described above, an adenoviral E1 sequence enhances cellular protein production. More preferably a cell line of the invention is provided wherein the cell line comprises a U-2 OS osteosarcoma, CHO, 293, HuNS-1 myeloma, WERI-Rb-1 retinoblastoma, BHK, Vero, non-secreting mouse myeloma Sp2/0-Ag 14, non-secreting mouse myeloma NSO, or NCI-H295R adrenal gland carcinoma (ATCC CRL-2128) cell line.

[0113]A cell line of the invention is particularly suitable for production of a proteinaceous molecule, because production can be enhanced by one or more STAR sequences (higher yield of a proteinaceous molecule, higher proportion of host cells with acceptable expression levels, and/or higher stability of a gene expression level). A cell line of the invention can comprise promiscuous, species-specific and/or cell type-specific STAR sequences. Furthermore, a cell line of the invention can be used to produce a heterologous proteinaceous molecule, and/or an affiliated proteinaceous molecule.

[0114]Hence, a use of a cell line of the invention for the production of a proteinaceous molecule is also herewith provided. Preferably, the proteinaceous molecule comprises an affiliated protein of the cell line.

[0115]Of course, a proteinaceous molecule obtainable by a method of the invention is also provided by the invention.

[0116]In one aspect, the invention provides a method for selecting a cell suitable for producing a proteinaceous molecule comprising: [0117]providing a nucleic acid encoding the proteinaceous molecule with a nucleic acid comprising a STAR sequence; [0118]expressing the resulting nucleic acid in the cell; and [0119]determining whether produced proteinaceous molecule has a desired property.

[0120]The desired property, for instance, comprises a pharmaceutical property. The property can be influenced by post translational modification(s), a configuration of a produced proteinaceous molecule, etc.

[0121]In yet another aspect, the invention provides a method for selecting a cell suitable for producing a proteinaceous molecule comprising: [0122]providing a host cell with a nucleic acid comprising a STAR sequence; [0123]selecting a cell with enhanced expression of a proteinaceous molecule; and [0124]determining whether the proteinaceous molecule has a desired property.

[0125]As has been discussed above, the nucleic acid comprising a STAR sequence can be randomly introduced into the genome of the host cell. Preferably, however, the nucleic acid sequence is introduced into the genome of the host cell by homologous recombination.

[0126]The invention is further explained in the following examples. The examples do not limit the invention in any way. They merely serve to clarify the invention.

EXAMPLES

Example 1

Method for Isolation of STAR Elements from the Human Genome

[0127]STAR elements are identified and cloned from human genomic DNA based on their ability to block the spread of transcriptional repression from DNA binding sites for repressor proteins in a test vector, as described in this example. The method described in this example is applicable in principle to any mammalian cell line, for isolation of both promiscuous and cell line-specific STAR elements.

A Method to Isolate Human STAR Elements Functional in U-2 OS Cell

Materials and Methods

[0128]Plasmids and strains. The selection vector for STAR elements, pSelect-SV40-zeo ("pSelect," FIG. 1) was constructed as follows: the pREP4 vector (Invitrogen V004-50) was used as the plasmid backbone. It provides the Epstein Barr oriP origin of replication and EBNA-1 nuclear antigen for high-copy episomal replication in primate cell lines; the hygromycin resistance gene with the thymidine kinase promoter and polyadenylation site, for selection in mammalian cells; and the ampicillin resistance gene and co1E1 origin of replication for maintenance in Escherichia coli. The vector contains four consecutive LexA operator sites between XbaI and NheI restriction sites (Bunker and Kingston, 1994). Embedded between the LexA operators and the NheI site is a polylinker consisting of the following restriction sites: HindIII-AscI-BamHI-AscI-HindIII. Between the NheI site and a SalI site is the zeocin resistance gene with the SV40 promoter and polyadenylation site, derived from pSV40/Zeo (Invitrogen V502-20); this is the selectable marker for the STAR screen.

[0129]Gene libraries were constructed by Sau3AI digestion of human genomic DNA, either purified from placenta (Clontech 6550-1) or carried in bacterial/P1 (BAC/PAC) artificial chromosomes. The BAC/PAC clones contain genomic DNA from the 1q12 cytogenetic region (clones RP1154H19 and RP3328E19), from the HOX cluster of homeotic genes (clones RP1167F23, RP1170019, and RP11387A1), or from human chromosome 22 (Research Genetics 96010-22). The DNAs were size-fractionated, and the 0.5-2 kb size fraction ligated into BamHI-digested pSelect vector, by standard techniques (Sambrook et al., 1989).

[0130]The construction of the host strains has been described (van der Vlag et al., 2000). Briefly, they are based on the U-2 OS human osteosarcoma cell line (American Type Culture Collection HTB-96). U-2 OS was stably transfected with the pTet-Off plasmid (Clontech K1620-A), encoding a protein chimera consisting of the Tet-repressor DNA binding domain and the VP16 transactivation domain. The cell line was subsequently stably transfected with fusion protein genes containing the LexA DNA binding domain, and the coding regions of HP1, MeCP2, or HPC2 (three Drosophila proteins that repress gene expression when tethered to DNA). The LexA-repressor genes are under control of the Tet-Off transcriptional regulatory system (Gossen and Bujard, 1992).

[0131]Library screening and STAR element characterization. The gene libraries in pSelect were transfected into U-2 OS/Tet-Off/LexA-repressor cell lines by calcium phosphate precipitation (Graham and van der Eb, 1973, Wigler et al., 1978) as recommended by the supplier of the transfection reagent (Life Technologies). Transfected cells were cultured under hygromycin selection (25 μg/ml) and tetracycline repression (doxycycline, 10 ng/ml) for one week (50% confluence). Then the doxycycline concentration was reduced to 0.1 ng/ml to induce the LexA-repressor genes, and after two days zeocin was added to 250 μg/ml. The cells are cultured for a further four to five weeks, until the control cultures (transfected with empty pSelect) were killed by the zeocin.

[0132]Zeocin-resistant colonies from the library transfection were propagated, and plasmid DNA isolated and rescued into E. coli by standard techniques (Sambrook et al., 1989). The candidate STAR elements in the rescued DNA were analyzed by restriction endonuclease mapping (Sambrook et al., 1989), and tested for STAR activity (zeocin resistance) after re-transfection to U-2 OS/Tet-Off/LexA-repressor cells and lowering the doxycycline concentration.

[0133]The human genomic DNA inserts in these plasmids were sequenced by the dideoxy method (Sanger et al., 1977) using a Beckman CEQ®2000 automated DNA sequencer, using the manufacturer's instructions. Briefly, DNA was purified from E. coli using QIAprep® Spin Miniprep and Plasmid Midi Kits (QIAGEN® 27106 and 12145, respectively). Cycle sequencing was carried out using custom oligonucleotides corresponding to the pSelect vector (primers D89 (SEQ ID NO:149) and D95 (SEQ ID NO:154); all oligonucleotides are described in Table 2), in the presence of dye terminators (CEQ® Dye Terminator Cycle Sequencing Kit, Beckman 608000). Assembled STAR DNA sequences were located in the human genome using BLAST (Basic Local Alignment Search Tool (Altschul et al., 1990); WorldWideWeb.ncbi.nlm.nih.gov/BLAST/).

Results

[0134]The screens of human genomic DNA have yielded 66 STAR elements; the lengths and chromosomal locations of these elements are tabulated in SEQ ID NO:1-SEQ ID NO:66. They confer zeocin resistance on U-2 OS host cells when placed between LexA-repressor binding sites and the zeocin resistance gene. Their anti-repression activity was demonstrated both in the initial screen and upon re-transfection (demonstrating that the anti-repression activity is due to the STAR element and not to somatic acquisition of zeocin resistance). The STAR elements correspond to known and unique sequences in the human genome, as demonstrated by BLAST searches (Table 3). In some cases, the cloned element is a chimera of two unlinked genomic loci (e.g., STAR3 (SEQ ID NO:3), Table 3). They range in length from 500 to 2361 base pairs in length.

Example 2

Predictability and Yield is Improved by Promiscuous STAR Elements in More than One Host Cell Line

[0135]STAR elements function to block the effect of transcriptional repression influences on transgene expression units. These repression influences can be due to heterochromatin ("position effects") or to adjacent copies of the transgene ("repeat-induced gene silencing"). Two of the benefits of STAR elements for heterologous protein production are increased predictability of finding high-expressing primary recombinant host cells and increased yield during production cycles. These benefits are illustrated in this example.

Materials and Methods

[0136]Construction of the pSDH vectors and STAR-containing derivatives: The pSDH-Tet vector was constructed by polymerase chain reaction amplification (PCR) of the luciferase open reading frame from plasmid pREP4-HSF-Luc (van der Vlag et al., 2000) using primers C67 (SEQ ID NO:136) and C68 (SEQ ID NO:137), and insertion of the SacII/BamHI fragment into SacII/BamHI-digested pUHD10-3 (Gossen and Bujard, 1992). The luciferase expression unit was re-amplified with primers C65 (SEQ ID NO:134) and C66 (SEQ ID NO:135), and re-inserted into pUHD10-3 in order to flank it with multiple cloning sites (MCSI and MCSII). An AscI site was then introduced into MCSI by digestion with EcoRI and insertion of a linker (comprised of annealed oligonucleotides D93 (SEQ ID NO:152) and D94 (SEQ ID NO:153)). The CMV promoter was amplified from plasmid pCMV-Bsd (Invitrogen K510-01) with primers D90 (SEQ ID NO:150) and D91 (SEQ ID NO:151), and used to replace the Tet-Off promoter in pSDH-Tet by SalI/SacII digestion and ligation to create vector pSDH-CMV. The luciferase open reading frame in this vector was replaced by SEAP (Secreted Alkaline Phosphatase) as follows: vector pSDH-CMV was digested with SacII and BamHI and made blunt; the SEAP open reading frame was isolated from pSEAP-basic (Clontech 6037-1) by EcoRI/SalI digestion, made blunt and ligated into pSDH-CMV to create vector pSDH-CS. The puromycin resistance gene under control of the SV40 promoter was isolated from plasmid pBabe-Puro (Morgenstern and Land, 1990) by PCR, using primers C81 (SEQ ID NO:138) and C82 (SEQ ID NO:139). This was ligated into vector pGL3-control (BamHI site removed) (Promega E1741) digested with NcoI/XbaI to create pGL3-puro. pGL3-puro was digested with BglII/SalI to isolate the SV40-puro resistance unit, which was made blunt and ligated into NheI digested, blunt-ended pSDH-CS. The resulting vector, pSDH-CSP, is shown in FIG. 2. All cloning steps were carried out following the instructions provided by the manufacturers of the reagents used, according to methods known in the art (Sambrook et al., 1989).

[0137]STAR elements were inserted into MCSI and MCSII in two steps, by digestion of the STAR element and the pSDH-CSP vector with an appropriate restriction enzyme, followed by ligation. The orientation of STAR elements in recombinant pSDH vectors was determined by restriction mapping, and in all cases verified by DNA sequence analysis using primers C85 (SEQ ID NO:140), E42 (SEQ ID NO:168), and E25 (SEQ ID NO:167) (Table 2; see Example 1).

[0138]Transfection and culture of U-2 OS cells with pSDH-CMV plasmids: The human osteosarcoma U-2 OS cell line (ATCC #HTB-96) was cultured in Dulbecco's Modified Eagle Medium+10% Fetal Calf Serum containing glutamine, penicillin, and streptomycin (supra) at 37° C./5% CO₂. Cells were co-transfected with the pSDH-CMV vector and its derivatives containing STAR6 (SEQ ID NO:6) or STAR8 (SEQ ID NO:8) in MCSI and MCSII (along with plasmid pBabe-Puro) using SuperFect® (supra). Puromycin selection was complete in two weeks, after which time individual puromycin resistant U-2 OS/pSDH-CMV clones were isolated at random and cultured further.

[0139]Luciferase assay: Luciferase activity (Himes and Shannon, 2000) was assayed in resuspended cells according to the instructions of the assay kit manufacturer (Roche 1669893), using a luminometer (Turner 20/20TD). Total cellular protein concentration was determined by the bicinchoninic acid method according to the manufacturer's instructions (Sigma B-9643), and used to normalize the luciferase data.

[0140]Transfection and culture of CHO cells with pSDH-CSP plasmids: The Chinese Hamster Ovary cell line CHO-K1 (ATCC CCL-61) was cultured in HAMS-F12 medium+10% Fetal Calf Serum containing 2 mM glutamine, 100 U/ml penicillin, and 100 micrograms/ml streptomcyin at 37° C./5% CO₂. Cells were transfected with recombinant pSDH-CSP vectors using SuperFect® (QIAGEN®) as described by the manufacturer. Briefly, cells were seeded to culture vessels and grown overnight to 70-90% confluence. SuperFect® reagent was combined with plasmid DNA (linearized in this example by digestion with PvuI) at a ratio of 6 microliters per microgram (e.g., for a 10 cm Petri dish, 20 micrograms DNA and 120 microliters SuperFect®) and added to the cells. After overnight incubation, the transfection mixture was replaced with fresh medium, and the transfected cells were incubated further. After overnight cultivation, 5 micrograms/ml puromycin was added. Puromycin selection was complete in two weeks, after which time individual puromycin resistant CHO/pSDH-CSP clones were isolated at random and cultured further.

[0141]Secreted Alkaline Phosphatase (SEAP) assay: SEAP activity (Berger et al., 1988, Henthorn et al., 1988, Kain, 1997, Yang et al., 1997) in the culture medium of CHO/pSDH-CSP clones was determined as described by the manufacturer (Clontech Great EscAPe kit #K2041). Briefly, an aliquot of medium was heat inactivated at 65° C., then combined with assay buffer and CSPD chemiluminescent substrate and incubated at room temperature for ten minutes. The rate of substrate conversion was then determined in a luminometer (Turner 20/20TD). Cell density was determined by counting trypsinized cells in a Coulter ACT10 cell counter. Luminescence units were converted into picograms SEAP based on a SEAP positive control calibration curve, and normalized to cell number.

Results

[0142]Recombinant U-2 OS cell clones containing the pSDH-CMV vector, or a pSDH-CMV plasmid containing STAR6 (SEQ ID NO:6) (Table 3), were cultured for three weeks. The luciferase activity in the host cells was then determined, and is expressed as relative luciferase units (FIG. 3), normalized to total cell protein. The recombinant U-2 OS clones with STAR6 (SEQ ID NO:6) flanking the expression units had higher yields than the STAR-less clones: the STAR6 clones had maximal luciferase expression levels five-fold higher than the STAR-less clones. The STAR6 (SEQ ID NO:6) element conferred greater predictability as well: 15-20% of the clones expressed luciferase at levels comparable to or greater than the STAR-less clone with the highest expression level.

[0143]Recombinant CHO cell clones containing the pSDH-CSP vector, or a pSDH-CSP plasmid containing STAR6 (SEQ ID NO:6), were cultured for three weeks. The SEAP activity in the culture supernatants was then determined, and is expressed on the basis of cell number (FIG. 4). As can be seen, clones with the STAR6 (SEQ ID NO:6) element in the expression units were isolated that express two- to three-fold higher SEAP activity than clones whose expression units do not include this STAR element. Furthermore, the number of STAR6-containing (SEQ ID NO:6-containing) clones that express SEAP activity at or above the maximal activity of the STAR-less clones is quite high: 40% of the STAR6 clone populations exceed the highest SEAP expression of the pSDH-CSP clones.

[0144]These results demonstrate that, when used with the strong CMV promoter, the STAR6 (SEQ ID NO:6) element increases the yield of this heterologous protein in both of the host cell lines tested. STAR6 (SEQ ID NO:6) also confers increased predictability, as manifested by the large proportion of the clones with yields equal to or greater than the highest yield displayed by the STAR-less clones. Thus, STAR6 (SEQ ID NO:6) is an example of a promiscuous STAR element, able to suppress transgene repression in more than one host cell line. The cell lines used are derived from different species (human and hamster) and different tissue types (bone and ovary), reflecting the broad range of host cells in which this STAR element can be utilized in improving heterologous protein expression.

Example 3

STAR8 (SEQ ID NO:8) is a Cell Line-Specific STAR Element

[0145]The patterns of gene expression and epigenetic gene regulation in a host cell line reflect the developmental state of the somatic cells from which they are derived. Furthermore, the biotechnology industry takes advantage of general purpose cell lines from different species according to specific requirements of a heterologous protein production process. Therefore, it is expected that some STAR elements will not function in cell lines other than those in which they are isolated. This expectation has been fulfilled by some of the STAR elements shown in Table 3. One example will be given here.

Materials and Methods

[0146]pSDH vector construction, transfection and cultivation of CHO and U-2 OS cell lines, and assay methods for the SEAP and luciferase reporter genes has been described in Example 2.

Results

[0147]Recombinant U-2 OS cell clones containing the pSDH-CMV vector, or a pSDH-CMV plasmid containing STAR8 (SEQ ID NO:8) (Table 3), were cultured for three weeks. The luciferase activity in the host cells was then determined, and is expressed as relative luciferase units (FIG. 3), normalized to total cell protein. The recombinant U-2 OS clones with the STAR8 (SEQ ID NO:8) element flanking the expression units had higher yields than the STAR-less clones: the highest expression observed from STAR8 clones was two- to three-fold higher than the expression from STAR-less clones. The STAR8 (SEQ ID NO:8) element conferred greater predictability as well: for this STAR element, ˜15% of the clones displayed luciferase expression at levels comparable to or greater than the STAR-less clone with the highest expression level.

[0148]Recombinant CHO cell clones transfected with the pSDH-CSP vector, or a pSDH-CSP plasmid containing STAR8 (SEQ ID NO:8), were cultured for three weeks. The SEAP activity in the culture supernatants was then determined, and is expressed on the basis of cell number (FIG. 4). As can be seen, one clone with the STAR8 (SEQ ID NO:8) element in the expression unit had a yield approximately two-fold higher than the highest-expressing STAR-less clone. However, the rest of the STAR8 clones expressed very poorly relative to the STAR-less clone population. Since only one individual in the STAR8 population had a good yield, it is probable that the expression unit in this clone was integrated in open, transcriptionally active chromatin, and the high yield does not reflect anti-repression activity of STAR8 (SEQ ID NO:8) in CHO cells. Certainly in the CHO clones transfected with STAR8-containing (SEQ ID NO:8-containing) expression units the predictability is quite poor; of the 17 puromycin-resistant clones, only one clone had a yield of SEAP activity above the background level of expression.

[0149]This example demonstrates that good performance of a STAR element in one cell line (in this case, the U-2 OS cell line in which STAR8 (SEQ ID NO:8) was originally isolated) is not an accurate predictor of its performance in other cell lines. STAR8 (SEQ ID NO:8) is thus an example of a cell line-specific STAR element.

Example 4

STAR Elements Functionality in Diverse Cell Line

Materials and Methods

[0150]Cell lines including the U-2 OS osteosarcoma and CHO (Chinese hamster ovary) cell lines (supra), the 293 cell line (ATCC CRL-1573) derived from human embryonal kidney (immortalized by adenovirus 5 transfection), the HuNS-1 myeloma (ATCC CRL-8644) and the WERI-Rb-1 retinoblastoma cell line (ATCC HTB-169), the NCI-H295R adrenal gland carcinoma (ATCC CRL-2128), and the non-secreting mouse myelomas Sp2/0-Ag 14 and NSO are examined according to the previous examples.

Example 5

STAR Elements Improve the Stability of Transgene Expression

[0151]During cultivation of recombinant host cells, it is common practice to maintain antibiotic selection. This is intended to prevent transcriptional silencing of the transgene, or loss of the transgene from the genome by processes such as recombination. However it is undesirable for production of heterologous proteins, for a number of reasons. First, the antibiotics that are used are quite expensive, and contribute significantly to the unit cost of the product. Second, for biopharmaceutical use, the protein must be demonstrably pure, with no traces of the antibiotic in the product. One advantage of STAR elements for heterologous protein production is that they confer stable expression on transgenes during prolonged cultivation, even in the absence of antibiotic selection; this property is demonstrated in this example.

Materials and Methods

[0152]The U-2 OS cell line was transfected with the plasmid pSDH-Tet-STAR6 and cultivated as described in Example 2. Individual puromycin-resistant clones were isolated and cultivated further in the absence of doxycycline. At weekly intervals the cells were transferred to fresh culture vessels at a dilution of 1:20. Luciferase activity was measured at periodic intervals as described in Example 2. After 15 weeks, the cultures were divided into two replicates; one replicate continued to receive puromycin, while the other replicate received no antibiotic for the remainder of the experiment (25 weeks total).

Results

[0153]Table 4 presents the data on luciferase expression by an expression unit flanked with STAR6 (SEQ ID NO:6) during prolonged growth with or without antibiotic. As can be seen, the expression of the reporter transgene, luciferase, remains stable in the U-2 OS host cells for the duration of the experiment. After the cultures were divided into two treatments (plus antibiotic and without antibiotic) the expression of luciferase was essentially stable in the absence of antibiotic selection. This demonstrates the ability of STAR elements to protect transgenes from silencing or loss during prolonged cultivation. It also demonstrates that this property is independent of antibiotic selection. Therefore, production of heterologous proteins is possible without incurring the costs of the antibiotic or of difficult downstream processing.

Example 6

Minimal Essential Sequences of STAR Elements

[0154]STAR elements are isolated from the genetic screen described in Example 1. The screen uses libraries constructed with human genomic DNA that was size-fractionated to approximately 0.5-2 kilobases (supra). The STAR elements range from 500 to 2361 base pairs (Table 3). It is likely that, for many of the STAR elements that have been isolated, STAR activity is conferred by a smaller DNA fragment than the initially isolated clone. It is useful to determine these minimum fragment sizes that are essential for STAR activity, for two reasons. First, smaller functional STAR elements would be advantageous in the design of compact expression vectors, since smaller vectors transfect host cells with higher efficiency. Second, determining minimum essential STAR sequences permits the modification of those sequences for enhanced functionality. Two STAR elements have been fine-mapped to determine their minimal essential sequences.

Materials and Methods

[0155]STAR10 (SEQ ID NO:10) (1167 base pairs) and STAR27 (SEQ ID NO:27) (1520 base pairs) have been fine-mapped. They have been amplified by PCR to yield sub-fragments of approximately equal length (FIG. 6 legend). For initial testing, these have been cloned into the pSelect vector at the BamHI site, and transfected into U-2 OS/Tet-Off/LexA-HP1 cells as described in Example 1. After selection for hygromycin resistance, LexA-HP1 was induced by lowering the doxycycline concentration. Transfected cells were then incubated with zeocin to test the ability of the STAR fragments to protect the SV40-Zeo expression unit from repression due to LexA-HP1 binding.

Results

[0156]In this experiment STAR10 (SEQ ID NO:10) and STAR 27 (SEQ ID NO:27) confer good protection against gene silencing, as expected (FIG. 6). This is manifested by robust growth in the presence of zeocin.

[0157]Of the three STAR10 (SEQ ID NO:10) sub-fragments, 10A (˜400 base pairs, corresponding to approximately the first 400 nucleotides of SEQ ID NO:10) confers on transfected cells vigorous growth in the presence of zeocin, exceeding that of the full-length STAR element. Cells transfected with pSelect constructs containing the other two sub-fragments do not grow in the presence of zeocin. These results identify the ˜400 base pair 10A fragment as encompassing the DNA sequence responsible for the anti-repression activity of STAR10 (SEQ ID NO:10).

[0158]STAR27 (SEQ ID NO:27) confers moderate growth in zeocin to transfected cells in this experiment (FIG. 6). One of the sub-fragments of this STAR, 27B (˜500 base pairs, corresponding to approximately the second 500 nucleotides of SEQ ID NO:27), permits weak growth of the host cells in zeocin-containing medium. This suggests that the anti-repression activity of this STAR is partially localized on sub-fragment 27B, but full activity requires sequences from 27A (corresponding to approximately the first 500 nucleotides of SEQ ID NO:27) and/or 27C (corresponding to approximately the third 500 nucleotides of SEQ ID NO:27) (each 500 base pairs) as well.

Example 7

STAR Elements Function in the Context of Various Transcriptional Promoters

[0159]Transgene transcription is achieved by placing the transgene open reading frame under control of an exogenous promoter. The choice of promoter is influenced by the nature of the heterologous protein and the production system. In most cases, strong constitutive promoters are preferred because of the high yields they can provide. Some viral promoters have these properties; the promoter/enhancer of the cytomegalovirus immediate early gene ("CMV promoter") is generally regarded as the strongest promoter in common biotechnological use (Boshart et al., 1985, Doll et al., 1996, Foecking and Hofstetter, 1986). The simian virus SV40 promoter is also moderately strong (Boshart et al., 1985, Foecking and Hofstetter, 1986) and is frequently used for ectopic expression in mammalian cell vectors. The Tet-Off promoter is inducible: the promoter is repressed in the presence of tetracycline or related antibiotics (doxycycline is commonly used) in cell-lines which express the tTA plasmid (Clontech K1620-A), and removal of the antibiotic results in transcriptional induction (Deuschle et al., 1995, Gossen and Bujard, 1992, Izumi and Gilbert, 1999, Umana et al., 1999).

Materials and Methods

[0160]The construction of the pSDH-Tet and pSDH-CMV vectors is described in Example 2. pSDH-SV40 was constructed by PCR amplification of the SV40 promoter (primers D41 (SEQ ID NO:142) and D42 (SEQ ID NO:143)) from plasmid pSelect-SV40-Zeo (Example 1), followed by digestion of the PCR product with SacII and SalI. The pSDH-CMV vector was digested with SacII and SalI to remove the CMV promoter, and the vector and SV40 fragment were ligated together to create pSDH-SV40. STAR6 (SEQ ID NO:6) was cloned into MCSI and MCSII as described in Example 2. The plasmids pSDH-Tet, pSDH-Tet-STAR6, pSDH-Tet-STAR7, pSDH-SV40 and pSDH-SV40-STAR6 were co-transfected with pBabe-Puro into U-2 OS using SuperFect® as described by the manufacturer. Cell cultivation, puromycin selection, and luciferase assays were carried out as described in Example 2.

Results

[0161]FIGS. 3, 7, and 8 compare the expression of the luciferase reporter gene from three different promoters: two strong and constitutive viral promoters (CMV and SV40), and the inducible Tet-Off promoter. All three promoters were tested in the context of the STAR6 (SEQ ID NO:6) element in U-2 OS cells. The results demonstrate that the yield and predictability from all three promoters are increased by STAR6 (SEQ ID NO:6). As described in Examples 2 and 5, STAR6 (SEQ ID NO:6) is beneficial in the context of the CMV promoter (FIG. 3). Similar improvements are seen in the context of the SV40 promoter (FIG. 7): the yield from the highest-expressing STAR6 clone is two- to three-fold greater than the best pSDH-SV40 clones, and six STAR clones (20% of the population) have yields higher than the best STAR-less clones. In the context of the Tet-Off promoter under inducing (low doxycycline) concentrations, STAR6 (SEQ ID NO:6) also improves the yield and predictability of transgene expression (FIG. 8): the highest-expressing STAR6 clone has a 20-fold higher yield than the best pSDH-Tet clone, and nine STAR6 clones (35% of the population) have yields higher than the best STAR-less clone. It is concluded that this STAR element is versatile in its transgene-protecting properties, since it functions in the context of various biotechnologically useful promoters of transcription.

Example 8

STAR Element Function can be Directional

[0162]While short nucleic acid sequences can be symmetrical (e.g., palindromic), longer, naturally-occurring sequences are typically asymmetrical. As a result, the information content of nucleic acid sequences is directional and the sequences themselves can be described with respect to their 5' and 3' ends. The directionality of nucleic acid sequence information affects the arrangement in which recombinant DNA molecules are assembled using standard cloning techniques known in the art (Sambrook et al., 1989). STAR elements are long, asymmetrical DNA sequences, and have a directionality based on the orientation in which they were originally cloned in the pSelect vector. In the examples given above, using two STAR elements in pSDH vectors, this directionality was preserved. This orientation is described as the native or 5'-3' orientation, relative to the zeocin resistance gene (see FIG. 9). In this example the importance of directionality for STAR function is tested in the pSDH-Tet vector. Since the reporter genes in the pSDH vectors are flanked on both sides by copies of the STAR element of interest, the orientation of each STAR copy must be considered. This example compares the native orientation with the opposite orientation (FIG. 9).

Materials and Methods

[0163]The STAR66 (SEQ ID NO:66) element was cloned into pSDH-Tet as described in Example 2. U-2 OS cells were co-transfected with plasmids pSDH-Tet-STAR66-native and pSDH-Tet-STAR66-opposite, and cultivated as described in Example 2. Individual clones were isolated and cultivated; the level of luciferase expression was determined as described (supra).

Results

[0164]The results of the comparison of STAR66 (SEQ ID NO:66) activity in the native orientation and the opposite orientation are shown in FIG. 10. When STAR66 (SEQ ID NO:66) is in the opposite orientation, the yield of only one clone is reasonably high (60 luciferase units). In contrast, the yield of the highest-expressing clone when STAR66 (SEQ ID NO:66) is in the native orientation is considerably higher (100 luciferase units) and the predictability is much higher, as well: seven clones of the native-orientation population (30%) express luciferase above the level of the highest-expressing clone from the opposite-orientation population, and 15 of the clones in the native-orientation population (60%) express luciferase above ten relative luciferase units. Therefore, it is demonstrated that STAR66 (SEQ ID NO:66) function is directional.

Example 9

Transgene Expression in the Context of STAR Elements is Copy Number-Dependent

[0165]Transgene expression units for heterologous protein expression are generally integrated into the genome of the host cell to ensure stable retention during cell division. Integration can result in one or multiple copies of the expression unit being inserted into the genome; multiple copies may or may not be present as tandem arrays. The increased yield demonstrated for transgenes protected by STAR elements (supra) suggests that STAR elements are able to permit the transgene expression units to function independently of influences on transcription associated with the site of integration in the genome (independence from position effects (Boivin and Dura, 1998)). It suggests further that the STAR elements permit each expression unit to function independently of neighboring copies of the expression unit when they are integrated as a tandem array (independence from repeat-induced gene silencing (Garrick et al., 1998)). Copy number-dependence is determined from the relationship between transgene expression levels and copy number, as described in the example below.

Materials and Methods

[0166]U-2 OS cells were co-transfected with pSDH-Tet-STAR10 and cultivated under puromycin selection as described (supra). Eight individual clones were isolated and cultivated further. Then cells were harvested, and one portion was assayed for luciferase activity as described (supra). The remaining cells were lysed and the genomic DNA purified using the DNeasy® Tissue Kit (QIAGEN® 69504) as described by the manufacturer. DNA samples were quantitated by UV spectrophotometry. Three micrograms of each genomic DNA sample were digested with PvuII and XhoI overnight as described by the manufacturer (New England Biolabs), and resolved by agarose gel electrophoresis. DNA fragments were transferred to a nylon membrane as described (Sambrook et al., 1989), and hybridized with a radioactively labeled probe to the luciferase gene (isolated from BamHI/SacII-digested pSDH-Tet). The blot was washed as described (Sambrook et al., 1989) and exposed to a phosphorimager screen (Personal F/X, BioRad). The resulting autoradiogram (FIG. 11) was analyzed by densitometry to determine the relative strength of the luciferase DNA bands, which represents the transgene copy number.

Results

[0167]The enzyme activities and copy numbers (DNA band intensities) of luciferase in the clones from the pSDH-Tet-STAR10 clone population is shown in FIG. 12. The transgene copy number is highly correlated with the level of luciferase expression in these pSDH-Tet-STAR10 clones (r=0.86). This suggests that STAR10 (SEQ ID NO:10) confers copy number-dependence on the transgene expression units, making transgene expression independent of other transgene copies in tandem arrays and independent of gene-silencing influences at the site of integration.

Example 10

STAR Elements Function as Enhancer Blockers but not Enhancers

[0168]Gene promoters are subject to both positive and negative influences on their ability to initiate transcription. An important class of elements that exert positive influences are enhancers. Enhancers are characteristically able to affect promoters even when they are located far away (many kilobase pairs) from the promoter. Negative influences that act by heterochromatin formation (e.g., Polycomb group proteins) have been described above, and these are the target of STAR activity. The biochemical basis for enhancer function and for heterochromatin formation is fundamentally similar, since they both involve binding of proteins to DNA. Therefore, it is important to determine whether STAR elements are able to block positive influences as well as negative influences, in other words, to shield transgenes from genomic enhancers in the vicinity of the site of integration. The ability to shield transgenes from enhancer activity ensures stable and predictable performance of transgenes in biotechnological applications. This example examines the performance of STAR elements in an enhancer-blocking assay.

[0169]Another feature of STAR activity that is important to their function is the increased yield they confer on transgenes (Example 2). STARs are isolated on the basis of their ability to maintain high levels of zeocin expression when heterochromatin-forming proteins are bound adjacent to the candidate STAR elements. High expression is predicted to occur because STARs are anticipated to block the spread of heterochromatin into the zeocin expression unit. However, a second scenario is that the DNA fragments in zeocin-resistant clones contain enhancers. Enhancers have been demonstrated to have the ability to overcome the repressive effects of Polycomb-group proteins such as those used in the method of the STAR screen (Zink and Paro, 1995). Enhancers isolated by this phenomenon would be considered false positives, since enhancers do not have the properties claimed here for STARs. In order to demonstrate that STAR elements are not enhancers, they have been tested in an enhancer assay.

[0170]The enhancer-blocking assay and the enhancer assay are methodologically and conceptually similar. The assays are shown schematically in FIG. 13. The ability of STAR elements to block enhancers is performed using the E47/E-box enhancer system. The E47 protein is able to activate transcription by promoters when it is bound to an E-box DNA sequence located in the vicinity of those promoters (Quong et al., 2002). E47 is normally involved in regulation of B and T lymphocyte differentiation (Quong et al., 2002), but it is able to function in diverse cell types when expressed ectopically (Petersson et al., 2002). The E-box is a palindromic DNA sequence, CANNTG (Knofler et al., 2002). In the enhancer-blocking assay, an E-box is placed upstream of a luciferase reporter gene (including a minimal promoter) in an expression vector. A cloning site for STAR elements is placed between the E-box and the promoter. The E47 protein is encoded on a second plasmid. The assay is performed by transfecting both the E47 plasmid and the luciferase expression vector into cells; the E47 protein is expressed and binds to the E-box, and the E47/E-box complex is able to act as an enhancer. When the luciferase expression vector does not contain a STAR element, the E47/E-box complex enhances luciferase expression (FIG. 13A, situation 1). When STAR elements are inserted between the E-box and the promoter, their ability to block the enhancer is demonstrated by reduced expression of luciferase activity (FIG. 13A, situation 2); if STARs cannot block enhancers, luciferase expression is activated (FIG. 13A, situation 3).

[0171]The ability of STAR elements to act as enhancers utilizes the same luciferase expression vector. In the absence of E47, the E-box itself does not affect transcription. Instead, enhancer behavior by STAR elements will result in activation of luciferase transcription. The assay is performed by transfecting the luciferase expression vector without the E47 plasmid. When the expression vector does not contain STAR elements, luciferase expression is low (FIG. 13B, situation 1). If STAR elements do not have enhancer properties, luciferase expression is low when a STAR element is present in the vector (FIG. 13B, situation 2). If STAR elements do have enhancer properties, luciferase expression will be activated in the STAR-containing vectors (FIG. 13B, situation 3).

Materials and Methods

[0172]The luciferase expression vector was constructed by inserting the E-box and a human alkaline phosphatase minimal promoter from plasmid mu-E5+E2x6-cat(x) (Ruezinsky et al., 1991) upstream of the luciferase gene in plasmid pGL3-basic (Promega E1751), to create pGL3-E-box-luciferase (gift of W. Romanow). The E47 expression plasmid contains the E47 open reading frame under control of a beta-actin promoter in the pHBAPr-1-neo plasmid; E47 in constitutively expressed from this plasmid (gift of W. Romanow).

[0173]STAR elements 1, 2, 3, 6, 10, 11, 18, and 27 (SEQ ID NOS:1, 2, 3, 6, 10, 11, 18, and 27, respectively) have been cloned into the luciferase expression vector. Clones containing the Drosophila scs element and the chicken beta-globin HS4-6x core ("HS4") element have been included as positive controls (they are known to block enhancers, and to have no intrinsic enhancer properties (Chung et al., 1993, Kellum and Schedl, 1992)), and the empty luciferase expression vector has been included as a negative control. All assays were performed using the U-2 OS cell line. In the enhancer-blocking assay, the E47 plasmid was co-transfected with the luciferase expression vectors (empty vector, or containing STAR or positive-control elements). In the enhancer assay, the E47 plasmid was co-transfected with STARless luciferase expression vector as a positive control for enhancer activity; all other samples received a mock plasmid during co-transfection. The transiently transfected cells were assayed for luciferase activity 48 hours after plasmid transfection (supra). The luciferase activity expressed from a plasmid containing no E-box or STAR/control elements was subtracted, and the luciferase activities were normalized to protein content as described (supra).

Results

[0174]FIG. 14 shows the results of the enhancer-blocking assay. In the absence of STAR elements (or the known enhancer-blocking elements scs and HS4), the E47/E-box enhancer complex activates expression of luciferase ("vector"); this enhanced level of expression has been normalized to 100. Enhancer activity is blocked by all STAR elements tested. Enhancer activity is also blocked by the HS4 and scs elements, as expected (Bell et al., 2001, Gerasimova and Corces, 2001). These results demonstrate that in addition to their ability to block the spreading of transcriptional silencing (negative influences), STAR elements are able to block the action of enhancers (positive influences).

[0175]FIG. 15 shows the results of the enhancer assay. The level of luciferase expression due to enhancement by the E47/E-box complex is set at 100 ("E47"). By comparison, none of the STAR elements bring about significant activation of luciferase expression. As expected, the scs and HS4 elements also do not bring about activation of the reporter gene. Therefore, it is concluded that at least the tested STAR elements do not possess enhancer properties.

Example 11

STAR Elements are Conserved Between Mouse and Human

[0176]BLAT analysis of the STAR DNA sequence against the human genome database (http://genome.ucsc.edu/cgi-bin/hgGateway) reveals that some of these sequences have high sequence conservation with other regions of the human genome. These duplicated regions are candidate STAR elements; if they do show STAR activity, they would be considered paralogs of the cloned STARs (two genes or genetic elements are said to be paralogous if they are derived from a duplication event (Li, 1997)).

[0177]BLAST analysis of the human STARs against the mouse genome (WorldWideWeb.ensembl.org/Mus_musculus/blastview) also reveals regions of high sequence conservation between mouse and human. This sequence conservation has been shown for fragments of 15 out of the 65 human STAR elements. The conservation ranges from 64% to 89%, over lengths of 141 base pairs to 909 base pairs (Table 5). These degrees of sequence conservation are remarkable and suggest that these DNA sequences may confer STAR activity within the mouse genome as well. Some of the sequences from the mouse and human genomes in Table 5 could be strictly defined as orthologs (two genes or genetic elements are said to be orthologous if they are derived from a speciation event (Li, 1997)). For example, STAR6 (SEQ ID NO:6) is between the SLC8A1 and HAAO genes in both the human and mouse genomes. In other cases, a cloned human STAR has a paralog within the human genome, and its ortholog has been identified in the mouse genome. For example, STAR3a is a fragment of the 15q11.2 region of human chromosome 15. This region is 96.9% identical (paralogous) with a DNA fragment at 5q33.3 on human chromosome 5, which is near the IL12B interleukin gene. These human DNAs share approximately 80% identity with a fragment of the 11B2 region on mouse chromosome 11. The 11B2 fragment is also near the (mouse) IL12B interleukin gene. Therefore, STAR3a and the mouse 11B2 fragment can be strictly defined as paralogs.

[0178]In order to test the hypothesis that STAR activity is shared between regions of high sequence conservation in the mouse and human genome, one of the human STARs with a conserved sequence in mouse, STAR18 (SEQ ID NO:18), has been analyzed in greater detail. The sequence conservation in the mouse genome detected with the original STAR18 clone extends leftward on human chromosome 2 for about 500 base pairs (FIG. 16; left and right relate to the standard description of the arms of chromosome 2). In this example, we examine whether the region of sequence conservation defines a "naturally occurring" STAR element in human that is more extensive in length than the original clone. We also examine whether the STAR function of this STAR element is conserved between mouse and human.

Materials and Methods

[0179]The region of mouse/human sequence conservation around STAR18 (SEQ ID NO:18) was recovered from human BAC clone RP11-387A1 by PCR amplification, in three fragments: the entire region (primers E93 (SEQ ID NO:171) and E94 (SEQ ID NO:172)), the leftward half (primers E93 (SEQ ID NO:171) and E92 (SEQ ID NO:170)), and the rightward half (primers E57 (SEQ ID NO:169) and E94 (SEQ ID NO:172)). The corresponding fragments from the homologous mouse region were recovered from BAC clone RP23-400H17 in the same fashion (primers E95 (SEQ ID NO:173) and E98 (SEQ ID NO:176), E95 (SEQ ID NO:173) and E96 (SEQ ID NO:174), and E97 (SEQ ID NO:175) and E98 (SEQ ID NO:176), respectively). All fragments were cloned into the pSelect vector and transfected into a U-2 OS/Tet-Off/LexA-HP1 cell line (supra). Following transfection, hygromycin selection was carried out to select for transfected cells. The LexA-HP1 protein was induced by lowering the doxycycline concentration, and the ability of the transfected cells to withstand the antibiotic zeocin (a measure of STAR activity) was assessed by monitoring cell growth.

Results

[0180]The original STAR18 clone was isolated from Sau3AI digested human DNA ligated into the pSelect vector on the basis of its ability to prevent silencing of a zeocin resistance gene. Alignment of the human STAR18 clone (497 base pairs) with the mouse genome revealed high sequence similarity (72%) between the orthologous human and mouse STAR18 (SEQ ID NO:18) regions. It also uncovered high similarity (73%) in the region extending for 488 base pairs immediately to the left of the Sau3AI site that defines the left end of the cloned region (FIG. 16). Outside these regions the sequence similarity between human and mouse DNA drops below 60%.

[0181]As indicated in FIG. 16, both the human and the mouse STAR18 (SEQ ID NO:18) elements confer survival on zeocin to host cells expressing the lexA-HP1 repressor protein. The original 497 base pair STAR18 clone and its mouse ortholog both confer the ability to grow (FIG. 16, a and d). The adjacent 488 base pair regions of high similarity from both genomes also confer the ability to grow, and in fact their growth phenotype is more vigorous than that of the original STAR18 clone (FIG. 16, b and e). When the entire region of sequence similarity was tested, these DNAs from both mouse and human confer growth, and the growth phenotype is more vigorous than the two sub-fragments (FIG. 16, c and f). These results demonstrate that the STAR activity of human STAR18 (SEQ ID NO:18) is conserved in its ortholog from mouse. The high sequence conservation between these orthologous regions is particularly noteworthy because they are not protein-coding sequences, leading to the conclusion that they have some regulatory function that has prevented their evolutionary divergence through mutation.

[0182]This analysis demonstrates that cloned STAR elements identified by the original screening program may in some cases represent partial STAR elements, and that analysis of the genomic DNA in which they are embedded can identify sequences with stronger STAR activity.

Example 12

STAR Elements Contain Characteristic DNA Sequence Motifs

[0183]STAR elements are isolated on the basis of their anti-repression phenotype with respect to transgene expression. This anti-repression phenotype reflects underlying biochemical processes that regulate chromatin formation which are associated with the STAR elements. These processes are typically sequence-specific and result from protein binding or DNA structure. This suggests that STAR elements will share DNA sequence similarity. Identification of sequence similarity among STAR elements will provide sequence motifs that are characteristic of the elements that have already been identified by functional screens and tests. The sequence motifs will also be useful to recognize and claim new STAR elements whose functions conform to the claims of this patent. The functions include improved yield and stability of transgenes expressed in eukaryotic host cells.

[0184]Other benefits of identifying sequence motifs that characterize STAR elements include: (1) provision of search motifs for prediction and identification of new STAR elements in genome databases, (2) provision of a rationale for modification of the elements, and (3) provision of information for functional analysis of STAR activity. Using bio-informatics, sequence similarities among STAR elements have been identified; the results are presented in this example.

Bio-Informatic and Statistical Background

[0185]Regulatory DNA elements typically function via interaction with sequence-specific DNA-binding proteins. Bio-informatic analysis of DNA elements, such as STAR elements whose regulatory properties have been identified, but whose interacting proteins are unknown, requires a statistical approach for identification of sequence motifs. This can be achieved by a method that detects short DNA sequence patterns that are over-represented in a set of regulatory DNA elements (e.g., the STAR elements) compared to a reference sequence (e.g., the complete human genome). The method determines the number of observed and expected occurrences of the patterns in each regulatory element. The number of expected occurrences is calculated from the number of observed occurrences of each pattern in the reference sequence.

[0186]The DNA sequence patterns can be oligonucleotides of a given length, e.g., six base pairs. In the simplest analysis, for a six-base-pair oligonucleotide (hexamer) composed of the four nucleotides (A, C, G, and T) there are 4⁶=4096 distinct oligonucleotides (all combinations from AAAAAA (SEQ ID NO:121) to TTTTTT (SEQ ID NO:122)). If the regulatory and reference sequences were completely random and had equal proportions of the A, C, G, and T nucleotides, then the expected frequency of each hexamer would be 1/4096 (˜0.00024). However, the actual frequency of each hexamer in the reference sequence is typically different than this due to biases in the content of G:C base pairs, etc. Therefore, the frequency of each oligonucleotide in the reference sequence is determined empirically by counting, to create a "frequency table" for the patterns.

[0187]The pattern frequency table of the reference sequence is then used to calculate the expected frequency of occurrence of each pattern in the regulatory element set. The expected frequencies are compared with the observed frequencies of occurrence of the patterns. Patterns that are "over-represented" in the set are identified; for example, if the hexamer ACGTGA (SEQ ID NO:123) is expected to occur five times in 20 kilobase pairs of sequence, but is observed to occur 15 times, then it is three-fold over-represented. Ten of the 15 occurrences of that hexameric sequence pattern would not be expected in the regulatory elements if the elements had the same hexamer composition as the entire genome. Once the over-represented patterns are identified, a statistical test is applied to determine whether their over-representation is significant, or may be due to chance. For this test, a significance index, "sig," is calculated for each pattern. The significance index is derived from the probability of occurrence of each pattern, which is estimated by a binomial distribution. The probability takes into account the number of possible patterns (4096 for hexamers). The highest sig values correspond to the most overrepresented oligonucleotides (van Helden et al., 1998). In practical terms, oligonucleotides with sig≧0 are considered as over-represented. A pattern with sig≧0 is likely to be over-represented due to chance once (=10⁰) in the set of regulatory element sequences. However, at sig≧1 a pattern is expected to be over-represented once in ten (=10¹) sequence sets, sig≧2 once in 100 (=10²) sequence sets, etc.

[0188]The patterns that are significantly over-represented in the regulatory element set are used to develop a model for classification and prediction of regulatory element sequences. This employs Discriminant Analysis, a so-called "supervised" method of statistical classification known to one of ordinary skill in the art (Huberty, 1994). In Discriminant Analysis, sets of known or classified items (e.g., STAR elements) are used to "train" a model to recognize those items on the basis of specific variables (e.g., sequence patterns such as hexamers). The trained model is then used to predict whether other items should be classified as belonging to the set of known items (e.g., is a DNA sequence a STAR element). In this example, the known items in the training set are STAR elements (positive training set). They are contrasted with sequences that are randomly selected from the genome (negative training set) which have the same length as the STAR elements. Discriminant Analysis establishes criteria for discriminating positives from negatives based on a set of variables that distinguish the positives; in this example, the variables are the significantly over-represented patterns (e.g., hexamers).

[0189]When the number of over-represented patterns is high compared to the size of the training set, the model could become biased due to over-training. Over-training is circumvented by applying a forward stepwise selection of variables (Huberty, 1994). The goal of Stepwise Discriminant Analysis is to select the minimum number of variables that provides maximum discrimination between the positives and negatives. The model is trained by evaluating variables one-by-one for their ability to properly classify the items in the positive and negative training sets. This is done until addition of new variables to the model does not significantly increase the model's predictive power (i.e., until the classification error rate is minimized). This optimized model is then used for testing, in order to predict whether "new" items are positives or negatives (Huberty, 1994).

[0190]It is inherent in classification statistics that for complex items such as DNA sequences, some elements of the positive training set will be classified as negatives (false negatives), and some members of the negative training set will be classified as positives (false positives). When a trained model is applied to testing new items, the same types of misclassifications are expected to occur.

[0191]In the bio-informatic method described here, the first step, Pattern Frequency Analysis, reduces a large set of sequence patterns (e.g., all 4096 hexamers) to a smaller set of significantly over-represented patterns (e.g., 100 hexamers); in the second step, Stepwise Discriminant Analysis reduces the set of over-represented patterns to the subset of those patterns that have maximal discriminative power (e.g., five to ten hexamers). Therefore, this approach provides simple and robust criteria for identifying regulatory DNA elements such as STAR elements.

[0192]DNA-binding proteins can be distinguished on the basis of the type of binding site they occupy. Some recognize contiguous sequences; for this type of protein, patterns that are oligonucleotides of length six base pairs (hexamers) are fruitful for bio-informatic analysis (van Helden et al., 1998). Other proteins bind to sequence dyads: contact is made between pairs of highly conserved trinucleotides separated by a non-conserved region of fixed width (van Helden et al., 2000). In order to identify sequences in STAR elements that may be bound by dyad-binding proteins, frequency analysis was also conducted for this type of pattern, where the spacing between the two trinucleotides was varied from 0 to 20 (i.e., XXXN{0-20}XXX where X's are specific nucleotides composing the trinucleotides, and N's are random nucleotides from 0 to 20 base pairs in length). The results of dyad frequency analysis are also used for Linear Discriminant Analysis as described above.

Materials and Methods

[0193]Using the genetic screen described in the original patent application, sixty-six (66) STAR elements were initially isolated from human genomic DNA and characterized in detail (Table 3). The screen was performed on gene libraries constructed by Sau3AI digestion of human genomic DNA, either purified from placenta (Clontech 6550-1) or carried in bacterial/P1 (BAC/PAC) artificial chromosomes. The BAC/PAC clones contain genomic DNA from regions of chromosome 1 (clones RP1154H19 and RP3328E19), from the HOX cluster of homeotic genes (clones RP1167F23, RP1170019, and RP11387A1), or from human chromosome 22 (Research Genetics 96010-22). The DNAs were size-fractionated, and the 0.5-2 kb size fraction was ligated into BamHI-digested pSelect vector, by standard techniques (Sambrook et al., 1989). pSelect plasmids containing human genomic DNA that conferred resistance to zeocin at low doxycycline concentrations were isolated and propagated in Escherichia coli. The screens that yielded the STAR elements of Table 3 have assayed approximately 1-2% of the human genome.

[0194]The human genomic DNA inserts in these 66 plasmids were sequenced by the dideoxy method (Sanger et al., 1977) using a Beckman CEQ®2000 automated DNA sequencer, using the manufacturer's instructions. Briefly, DNA was purified from E. coli using QIAprep® Spin Miniprep and Plasmid Midi Kits (QIAGEN® 27106 and 12145, respectively). Cycle sequencing was carried out using custom oligonucleotides corresponding to the pSelect vector (primers D89 (SEQ ID NO:149) and D95 (SEQ ID NO:154), Table 2), in the presence of dye terminators (CEQ® Dye Terminator Cycle Sequencing Kit, Beckman 608000). Assembled STAR DNA sequences were located in the human genome (database builds August and December 2001) using BLAT (Basic Local Alignment Tool (Kent, 2002); http://genome.ucsc.edu/cgi-bin/hgGateway; Table 3). In aggregate, the combined STAR sequences comprise 85.6 kilobase pairs, with an average length of 1.3 kilobase pairs.

[0195]Sequence motifs that distinguish STAR elements within human genomic DNA were identified by bio-informatic analysis using a two-step procedure, as follows (see FIG. 17 for a schematic diagram). The analysis has two input datasets: (1) the DNA sequences of the STAR elements (STAR1-STAR65 (SEQ ID NOS:1-65) were used; Table 3); and (2) the DNA sequence of the human genome (except for chromosome 1, which was not feasible to include due to its large size; for dyad analysis a random subset of human genomic DNA sequence (˜27 Mb) was used).

Pattern Frequency Analysis

[0196]The first step in the analysis uses RSA-Tools software (Regulatory Sequence Analysis Tools; WorldWideWeb.ucmb.ulb.ac.be/bioinformatics/rsa-tools/; references (van Helden et al., 1998, van Helden et al., 2000, van Helden et al., 2000)) to determine the following information: (1) the frequencies of all dyads and hexameric oligonucleotides in the human genome; (2) the frequencies of the oligonucleotides and dyads in the 65 STAR elements; and (3) the significance indices of those oligonucleotides and dyads that are over-represented in the STAR elements compared to the genome. A control analysis was done with 65 sequences that were selected at random from the human genome (i.e., from 2689×10³ kilobase pairs) that match the length of the STAR elements of Table 3.

Discriminant Analysis

[0197]The over-represented oligonucleotides and dyads were used to train models for prediction of STAR elements by Linear Discriminant Analysis (Huberty, 1994). A pre-selection of variables was performed by selecting the 50 patterns with the highest individual discriminatory power from the over-represented oligos or dyads of the frequency analyses. These pre-selected variables were then used for model training in a Stepwise Linear Discriminant Analysis to select the most discriminant combination of variables (Huberty, 1994). Variable selection was based on minimizing the classification error rate (percentage of false negative classifications). In addition, the expected error rate was estimated by applying the same discriminant approach to the control set of random sequences (minimizing the percentage of false positive classifications).

[0198]The predictive models from the training phase of Discriminant Analysis were tested in two ways. First, the STAR elements and random sequences that were used to generate the model (the training sets) were classified. Second, sequences in a collection of 19 candidate STAR elements (recently cloned by zeocin selection as described above) were classified. These candidate STAR elements are listed in Table 8 (SEQ ID NOS:66-84).

Results

[0199]Pattern frequency analysis was performed with RSA-Tools on 65 STAR elements, using the human genome as the reference sequence. One hundred sixty-six (166) hexameric oligonucleotides were found to be over-represented in the set of STAR elements (sig≧0) compared to the entire genome (Table 6). The most significantly over-represented oligonucleotide, CCCCAC (SEQ ID NO:177), occurs 107 times among the 65 STAR elements, but is expected to occur only 49 times. It has a significance coefficient of 8.76; in other words, the probability that its over-representation is due to random chance is 1/10⁸.76, i.e., less than one in 500 million.

[0200]Ninety-five of the oligonucleotides have a significance coefficient greater than one, and are, therefore, highly over-represented in the STAR elements. Among the over-represented oligonucleotides, their observed and expected occurrences, respectively, range from 6 and 1 (for oligo 163, CGCGAA (SEQ ID NO:339), sig=0.02) to 133 and 95 (for oligo 120, CCCAGG (SEQ ID NO:296), sig=0.49). The differences in expected occurrences reflect factors such as the G:C content of the human genome. Therefore, the differences among the oligonucleotides in their number of occurrences is less important than their over-representation; for example, oligo 2 (CAGCGG (SEQ ID NO:178)) is 36/9=four-fold over-represented, which has a probability of being due to random chance of one in fifty million (sig=7.75).

[0201]Table 6 also presents the number of STAR elements in which each over-represented oligonucleotide is found. For example, the most significant oligonucleotide, oligo 1 (CCCCAC (SEQ ID NO:177)), occurs 107 times, but is found in only 51 STARs, i.e., on average it occurs as two copies per STAR. The least abundant oligonucleotide, number 166 (AATCGG (SEQ ID NO:342)), occurs on average as a single copy per STAR (thirteen occurrences on eleven STARs); single-copy oligonucleotides occur frequently, especially for the lower-abundance oligos. At the other extreme, oligo 4 (CAGCCC (SEQ ID NO:527)) occurs on average three times in those STARs in which it is found (37 STARs). The most widespread oligonucleotide is number 120 (CCCAGG (SEQ ID NO:296)), which occurs on 58 STARs (on average twice per STAR), and the least widespread oligonucleotide is number 114 (CGTCGC (SEQ ID NO:290)), which occurs on only six STARs (and on average only once per STAR).

[0202]Results of dyad frequency analysis are given in Table 7. Seven hundred thirty (730) dyads were found to be over-represented in the set of STAR elements (sig≧0) compared to the reference sequence. The most significantly over-represented dyad, CCCN{2}CGG (SEQ ID NO:343), occurs 36 times among the 65 STAR elements, but is expected to occur only seven times. It has a significance coefficient of 9.31; in other words, the probability that its over-representation is due to chance is 1/10⁹.31, i.e., less than one in two billion.

[0203]Three hundred ninety-seven (397) of the dyads have a significance coefficient greater than 1, and are, therefore, highly over-represented in the STAR elements. Among the over-represented dyads, their observed and expected occurrences, respectively, range from 9 and 1 (for five dyads (numbers 380, 435, 493, 640, and 665)) to 118 and 63 (for number 30 (AGGN{2}GGG (SEQ ID NO:372)), sig=4.44).

[0204]The oligonucleotides and dyads found to be over-represented in STAR elements by pattern frequency analysis were tested for their discriminative power by Linear Discriminant Analysis. Discriminant models were trained by step-wise selection of the best combination among the 50 most discriminant oligonucleotide (Table 6) or dyad (Table 7) patterns. The models achieved optimal error rates after incorporation of four (dyad) or five variables. The discriminative variables from oligo analysis are numbers 11, 30, 94, 122, and 160 (Table 6); those from dyad analysis are numbers 73, 194, 419, and 497 (Table 7).

[0205]The discriminant models were then used to classify the 65 STAR elements in the training set and their associated random sequences. The model using oligonucleotide variables classifies 46 of the 65 STAR elements as STAR elements (true positives); the dyad model classifies 49 of the STAR elements as true positives. In combination, the models classify 59 of the 65 STAR elements as STAR elements (91%; FIG. 18). The false positive rates (random sequences classified as STARs) were seven for the dyad model, eight for the oligonucleotide model, and 13 for the combined predictions of the two models (20%). The STAR elements of Table 3 that were not classified as STARs by LDA are STAR7, STAR22, STAR35, STAR44, STAR46, and STAR65 (SEQ ID NOS:7, 22, 35, 44, 46 and 65, respectively). These elements display stabilizing anti-repressor activity in functional assays, so the fact that they are not classified as STARs by LDA suggests that they represent another class (or classes) of STAR elements.

[0206]The models were then used to classify the 19 candidate STAR elements in the testing set listed in Table 8. The dyad model classifies 12 of these candidate STARs as STAR elements, and the oligonucleotide model classifies 14 as STARs. The combined number of the candidates that are classified as STAR elements is 15 (79%). This is a lower rate of classification than obtained with the training set of 65 STARs; this is expected for two reasons. First, the discriminant models were trained with the 65 STARs of Table 3, and discriminative variables based on this training set may be less well represented in the testing set. Second, the candidate STAR sequences in the testing set have not yet been fully characterized in terms of in vivo function, and may include elements with only weak anti-repression properties.

[0207]This analysis demonstrates the power of a statistical approach to bio-informatic classification of STAR elements. The STAR sequences contain a number of dyad and hexameric oligonucleotide patterns that are significantly over-represented in comparison with the human genome as a whole. These patterns may represent binding sites for proteins that confer STAR activity; in any case they form a set of sequence motifs that can be used to recognize STAR element sequences.

[0208]Using these patterns to recognize STAR elements by Discriminant Analysis, a high proportion of the elements obtained by the genetic screen of the invention are in fact classified as STARs. This reflects underlying sequence and functional similarities among these elements. An important aspect of the method described here (pattern frequency analysis followed by Discriminant Analysis) is that it can be reiterated; for example, by including the 19 candidate STAR elements of Table 8 with the 66 STAR elements of Table 3 into one training set, an improved discriminant model can be trained. This improved model can then be used to classify other candidate regulatory elements as STARs. Large-scale in vivo screening of genomic sequences using the method of the invention, combined with reiteration of the bio-informatic analysis, will provide a means of discriminating STAR elements that asymptotically approaches 100% recognition and prediction of elements as the genome is screened in its entirety. These stringent and comprehensive predictions of STAR function will ensure that all human STAR elements are recognized, and are available for use in improving transgene expression.

Example 13

Cloning and Characterization of STAR Elements from Arabidopsis thaliana

[0209]Transgene silencing occurs in transgenic plants at both the transcriptional and post-transcriptional levels (Meyer, 2000, Vance and Vaucheret, 2001). In either case, the desired result of transgene expression can be compromised by silencing; the low expression and instability of the transgene results in poor expression of desirable traits (e.g., pest resistance) or low yields of recombinant proteins. It also results in poor predictability: the proportion of transgenic plants that express the transgene at biotechnologically useful levels is low, which necessitates laborious and expensive screening of transformed individuals for those with beneficial expression characteristics. This example describes the isolation of STAR elements from the genome of the dicot plant Arabidopsis thaliana for use in preventing transcriptional transgene silencing in transgenic plants. Arabidopsis was chosen for this example because it is a well-studied model organism: it has a compact genome, it is amenable to genetic and recombinant DNA manipulations, and its genome has been sequenced (Bevan et al., 2001, Initiative, 2000, Meinke et al., 1998).

Materials and Methods

[0210]Genomic DNA was isolated from Arabidopsis thaliana ecotype Columbia as described (Stam et al., 1998) and partially digested with MboI. The digested DNA was size-fractionated to 0.5-2 kilobase pairs by agarose gel electrophoresis and purification from the gel (QIAquick® Gel Extraction Kit, QIAGEN® 28706), followed by ligation into the pSelect vector (supra). Transfection into the U-2 OS/Tet-Off/LexA-HP1 cell line and selection for zeocin resistance at low doxycycline concentration was performed as described (supra). Plasmids were isolated from zeocin resistant colonies and re-transfected into the U-2 OS/Tet-Off/LexA-HP1 cell line.

[0211]Sequencing of Arabidopsis genomic DNA fragments that conferred zeocin resistance upon re-transfection was performed as described (supra). The DNA sequences were compared to the sequence of the Arabidopsis genome by BLAST analysis ((Altschul et al., 1990); URL WorldWideWeb.ncbi.nlm.nih.gov/blast/Blast).

[0212]STAR activity was tested further by measuring mRNA levels for the hygromycin- and zeocin-resistance genes in recombinant host cells by reverse transcription PCR (RT-PCR). Cells of the U-2 OS/Tet-Off/lexA-HP1 cell line were transfected with pSelect plasmids containing Arabidopsis STAR elements, the Drosophila scs element, or containing no insert (supra). These were cultivated on hygromycin for two weeks at high doxycycline concentration, then the doxycycline concentration was lowered to 0.1 ng/ml to induce the lexA-HP1 repressor protein. After ten days, total RNA was isolated by the RNeasy® mini kit (QIAGEN® 74104) as described by the manufacturer. First-strand cDNA synthesis was carried out using the RevertAid® First Strand cDNA Synthesis kit (MBI Fermentas 1622) using oligo(dT) 18 primer as described by the manufacturer. An aliquot of the cDNA was used as the template in a PCR reaction using primers D58 (SEQ ID NO:145) and D80 (SEQ ID NO:148) (for the zeocin marker), and D70 (SEQ ID NO:146) and D71 (SEQ ID NO:147) (for the hygromycin marker), and Taq DNA polymerase (Promega M2661). The reaction conditions were 15-20 cycles of 94° C. for one minute, 54° C. for one minute, and 72° C. for 90 seconds. These conditions result in a linear relationship between input RNA and PCR product DNA. The PCR products were resolved by agarose gel electrophoresis, and the zeocin and hygromycin bands were detected by Southern blotting as described (Sambrook et al., 1989), using PCR products produced as above with purified pSelect plasmid as template. The ratio of the zeocin and hygromycin signals corresponds to the normalized expression level of the zeocin gene.

Results

[0213]The library of Arabidopsis genomic DNA in the pSelect vector comprised 69,000 primary clones in E. coli, 80% of which carried inserts. The average insert size was approximately 1000 base pairs; the library, therefore, represents approximately 40% of the Arabidopsis genome.

[0214]A portion of this library (representing approximately 16% of the Arabidopsis genome) was transfected into the U-2 OS/Tet-Off/LexA-HP1 cell line. Hygromycin selection was imposed to isolate transfectants, which resulted in 27,000 surviving colonies. These were then subjected to zeocin selection at low doxycycline concentration. Putative STAR-containing plasmids from 56 zeocin-resistant colonies were rescued into E. coli and re-transfected into U-2 OS/Tet-Off/LexA-HP1 cells. Forty-four of these plasmids (79% of the plasmids tested) conferred zeocin resistance on the host cells at low doxycycline concentrations, demonstrating that the plasmids carried STAR elements. This indicates that the pSelect screen in human U-2 OS cells is highly efficient at detection of STAR elements from plant genomic DNA.

[0215]The DNA sequences of these 44 candidate STAR elements were determined. Thirty-five of them were identified as single loci in the database of Arabidopsis nuclear genomic sequence (Table 9; SEQ ID NO:85-SEQ ID NO:119). Four others were identified as coming from the chloroplast genome, four were chimeras of DNA fragments from two loci, and one was not found in the Arabidopsis genome database.

[0216]The strength of the cloned Arabidopsis STAR elements was tested by assessing their ability to prevent transcriptional repression of the zeocin-resistance gene, using an RT-PCR assay. As a control for RNA input among the samples, the transcript levels of the hygromycin-resistance gene for each STAR transfection were assessed too. This analysis has been performed for 12 of the Arabidopsis STAR elements. The results (FIG. 19) demonstrate that the Arabidopsis STAR elements are superior to the Drosophila scs element (positive control) and the empty vector ("SV40"; negative control) in their ability to protect the zeocin-resistance gene from transcriptional repression. In particular, STAR-A28 (SEQ ID NO:112) and STAR-A30 (SEQ ID NO:114) enable two-fold higher levels of zeocin-resistance gene expression than the scs element (normalized to the internal control of hygromycin-resistance gene mRNA) when the lexA-HP1 repressor is expressed.

[0217]These results demonstrate that the method of the invention can be successfully applied to recovery of STAR elements from genomes of other species than human. Its successful application to STAR elements from a plant genome is particularly significant because it demonstrates the wide taxonomic range over which the method of the invention is applicable and because plants are an important target of biotechnological development.

Example 14

STAR Elements Function in CHO Cells

[0218]STAR elements function to block the effect of transcriptional repression influences on transgene expression units. Two of the benefits of STAR elements for heterologous protein production are an increased predictability to find high-expressing primary recombinant host cells as well as increased protein production or yield in these cells. Importantly, the disclosed STAR elements are human DNA sequences, isolated in the human U-2 OS osteosarcoma cell line. It is, therefore, an important question whether the human STAR elements are functional in a) cell lines derived from species other than man, and/or in b) human cell lines other than the U-2 OS osteosarcoma cell line. In this example the functionality of STAR 7 (SEQ ID NO:7) in (CHO) Chinese hamster ovary are illustrated.

Material and Methods

[0219]The STAR7 (SEQ ID NO:7) element is tested in the ppGIZ-STAR7 vector (FIG. 20). The construction of the pPlug&Play-GFP-ires-Zeo (ppGIZ) vector is described below. Plasmid pGFP (Clontech 6010-1) is modified by insertion of a linker at the BsiWI site to yield pGFP-link. The linker (made by annealing oligonucleotides 5' GTACGGATATCAGATCTTTAATTAAG 3' (SEQ ID NO:124) and 5' GTACCTTAATTAAAGATCTGATATCC 3' (SEQ ID NO:125)) introduces sites for the PacI, BglII, and EcoRV restriction endonucleases. This creates the multiple cloning site MCSII for insertion of STAR elements. Then primers 5' ATCAGATCTGGCGCGCCATTTAAATCGTC TCGCGCGTTTCGGTGATGACGG 3' (SEQ ID NO:126) and 5' AGGCGGATCCGAATG TATTTAGAAAAATAAACAAATAGGGG 3' (SEQ ID NO:127) are used to amplify a region of 0.37 kb from pGFP, which is inserted into the BglII site of pIRES (Clontech 6028-1) to yield pIRES-stuf. This introduces sites for the AscI and SwaI restriction endonucleases at MCSI, and acts as a "stuffer fragment" to avoid potential interference between STAR elements and adjacent promoters. pIRES-stuf is digested with BglII and FspI to liberate a DNA fragment composed of the stuffer fragment, the CMV promoter, the IRES element (flanked by multiple cloning sites MCS A and MCS B), and the SV40 polyadenylation signal. This fragment is ligated with the vector backbone of pGFP-link produced by digestion with BamHI and StuI, to yield pIRES-link.

[0220]The open reading frames of the zeocin-resistance gene is inserted into the BamHI/NotI sites of MCS B in pIRES-link as follows: the zeocin-resistance ORF is amplified by PCR with primers 5' GATCGGATCCTTCGAAATGGCCAAGTTGACCAGTGC 3' (SEQ ID NO:128) and 5' AGGCGCGGCCGCAATTCTCAGTCCTGCTCCTC 3' (SEQ ID NO:129) from plasmid pEM7/zeo, digested with BamHI and NotI, and ligated with BamHI/NotI-digested pIRES-link to yield pIRES-link-zeo. The GFP reporter ORF was introduced into pIRES-link-zeo by amplification of phr-GFP-1 with primers 5' GATCGAATTCTCGCGAATGGTGAGCAAGCAGATCCTGAAG 3' (SEQ ID NO:130) and 5' AGGCGAATTCACCGGTGTTTAAACTTACACCCACTCGTGCAGGCTGCCCAGG 3' (SEQ ID NO:131), and insertion of the EcoRI-digested GFP cassette into the EcoRI site in MCS A of the pIRES-link-zeo plasmid. This created the ppGIZ (for ppGFP-IRES-zeo). STAR7 (SEQ ID NO:7) is cloned into the SalI site (5') and into the PacI site (3').

Transfection and Culture of CHO Cells

[0221]The Chinese Hamster Ovary cell line CHO-K1 (ATCC CCL-61) is cultured in HAMS-F12 medium+10% Fetal Calf Serum containing 2 mM glutamine, 100 U/ml penicillin, and 100 micrograms/ml streptomycin at 37° C./5% CO₂. Cells are transfected with the plasmids using Lipofectamine 2000 (Invitrogen) as described by the manufacturer. Briefly, cells are seeded to culture vessels and grown overnight to 70-90% confluence. Lipofectamine reagent is combined with plasmid DNA at a ratio of 7.5 microliters per 3 microgram (e.g., for a 10 cm Petri dish, 20 micrograms DNA and 120 microliters Lipofectamine) and added after a 30-minute incubation at 25° C. to the cells. After a six-hour incubation, the transfection mixture is replaced with fresh medium, and the transfected cells are incubated further. After overnight cultivation, cells are trypsinized and seeded into fresh petri dishes with fresh medium with zeocin added to a concentration of 100 μg/ml and the cells are cultured further. When individual colonies become visible (approximately ten days after transfection) medium is removed and replaced with fresh medium without zeocin. Individual clones are isolated and transferred to 24-well plates in medium with zeocin. Expression of the GFP reporter gene is assessed approximately three weeks after transfection.

[0222]The tested constructs consist of a bicistronic gene with the GFP gene, an IRES and the Zeocin resistance gene under control of the CMV promoter, but either with or without STAR7 (SEQ ID NO:7) element to flank the entire construct (FIG. 20). The constructs are transfected to CHO-K1 cells. Stable colonies are expanded before the GFP signal is determined on a XL-MCL Beckman Coulter flow cytometer. The mean of the GFP signal is taken as measure for the level of GFP expression and this is plotted in FIG. 20.

Results

[0223]FIG. 20 shows that flanking a GFP reporter gene that is under the control of the CMV promoter results in a higher number of CHO colonies that express significantly higher levels of GFP protein, as compared to the control without STAR7 (SEQ ID NO:7) element. The STAR7 (SEQ ID NO:7) element, therefore, conveys a higher degree of predictability of transgene expression in CHO cells. The highest GFP expression level in STAR-shielded CHO colonies is also higher than in STAR-less control colonies. In addition, when the tested colonies were further grown for another 30 days without Zeocin in the culture medium, the GFP expression levels in the STAR-shielded colonies remained equally high, whereas the GFP expression levels in the STAR-less colonies dropped to at feast below 50% of the original values. It is, therefore, concluded that STAR7 (SEQ ID NO:7) is able to convey higher as well as more stable expression levels to a transgene in CHO cells, this being a cell line derived from another species than man.

Example 15

STAR Elements Function in NSO Cells

[0224]STAR elements function to block the effect of transcriptional repression influences on transgene expression units. Two of the benefits of STAR elements for heterologous protein production are an increased predictability to find high-expressing primary recombinant host cells, as well as increased protein production or yield in these cells. Importantly, the disclosed STAR elements are human DNA sequences, isolated in the human U-2 OS osteosarcoma cell line. It is, therefore, an important question whether the human STAR elements are functional in a) cell lines derived from species other than man, and/or in b) human cell lines other than the U-2 OS osteosarcoma cell line. In this example the functionality of STAR 7 (SEQ ID NO:7) in non-secreting mouse myeloma (NSO) cells are illustrated.

Materials and Methods

[0225]The tested constructs are the same as described in Example 14. NSO (Non-Secreting mouse myeloma) cells (ECACC 85110503) are suspension cells that are cultured in RPMI 1640 medium+10% Fetal Calf Serum containing 2 mM glutamine, 100 U/ml penicillin, and 100 micrograms/ml streptomycin at 37° C./5% CO₂. Cells are transfected with the plasmids using Lipofectamine 2000 (Invitrogen) as described by the manufacturer. Briefly, cells are seeded to culture vessels and grown overnight to 4×10⁵/ml. Lipofectamine reagent is combined with plasmid DNA at a ratio of 3 microliters per microgram DNA (e.g., for a 10 cm Petri dish, 20 micrograms DNA and 60 microliters Lipofectamine) and added after 30 minutes incubation at 25° C. temperature to the cells. After overnight incubation, the transfection mixture is replaced with fresh medium and the transfected cells are incubated further. After another overnight incubation, zeocin is added to a concentration of 100 μg/ml and the cells are cultured and further incubated for three days. Then the cells are seeded in 96-well plates in such dilutions that one well will contain ˜1 cell. After ten days growing colonies are transferred to 24-well plates.

Results

[0226]FIG. 21 shows that flanking a GFP reporter gene that is under the control of the CMV promoter results in a higher number of NSO colonies that express significantly higher levels of GFP protein, as compared to the control without STAR7 (SEQ ID NO:7) element. The STAR7 (SEQ ID NO:7) element, therefore, conveys a higher degree of predictability of transgene expression in NSO cells. The highest GFP expression level in STAR-shielded NSO colonies is also higher than in STAR-less control colonies. It is, therefore, concluded that STAR7 (SEQ ID NO:7) is able to convey higher expression levels to a transgene in NSO cells, this being a cell line derived from another species than man.

Example 16

STAR Elements Function in Human 293 Cells

[0227]STAR elements function to block the effect of transcriptional repression influences on transgene expression units. Two of the benefits of STAR elements for heterologous protein production are an increased predictability to find high-expressing primary recombinant host cells as well as increased protein production or yield in these cells. Importantly, the disclosed STAR elements are human DNA sequences, isolated in the human U-2 OS osteosarcoma cell line. It is, therefore, an important question whether the human STAR elements are functional in a) cell lines derived from species other than man, and/or in b) human cell lines other than the U-2 OS osteosarcoma cell line. In this example, the functionality of STAR7 (SEQ ID NO:7) in human 293 cells are illustrated.

Materials and Methods

[0228]The tested constructs are the same as described in Example 14. The 293 cell line (ATCC CRL-1573) is derived from human embryonal kidney (immortalized by adenovirus 5 transfection) and is cultured in Dulbecco's Modified Eagle Medium+10% Fetal Calf Serum containing 2 mM glutamine, 100 U/ml penicillin, and 100 micrograms/ml streptomycin at 37° C./5% CO₂. Cells are transfected with the plasmids using Lipofectamine 2000 (Invitrogen) as described by the manufacturer. Selection and propagation of the 293 colonies are as described in Example 14 for U-2 OS cells.

Results

[0229]FIG. 22 shows that flanking a GFP reporter gene that is under the control of the CMV promoter results in a higher number of 293 colonies that express significantly higher levels of GFP protein, as compared to the control without STAR7 (SEQ ID NO:7) element. The STAR7 (SEQ ID NO:7) element, therefore, conveys a higher degree of predictability of transgene expression in 293 cells. The highest GFP expression level in STAR-shielded colonies is also higher than in STAR-less control colonies. It is, therefore, concluded that STAR7 (SEQ ID NO:7) is able to convey higher expression levels to a transgene in 293 cells, this being another human cell line, distinct from the human U-2 OS cell line.

TABLE-US-00001 TABLE 1 Biopharmaceutical Proteins, Their Tissue or Cell Type of Origin Protein Tissue/Somatic Cells Cell Lines (ATCC #)¹ Indications alpha-1 Antitrypsin Liver, leukocytes Hep G2 (HB-8065) Cystic fibrosis, emphysema alpha-Galactosidase A; -Glucosidase Fibroblasts WI 38 (CCL-75) Fabry disease; Pompe's disease Antibodies (monoclonal, Lymphocytes Transfectomas Various therapeutic single-chain, etc) strategies Antithrombin III Liver Hep G2 (HB-8065) Thrombophilia Calcitonin Thyroid (parafollicular cells) TT (CRL-1803) Osteoporosis Ciliary neurotrophic factor Neural tissue (e.g., astrocytes) HCN-1A (CRL-10442) Motor neuron disease Epidermal Growth Factor Kidney G-401 (CRL-1441) Wound healing Erythropoietin Liver, kidney Hep G2 (HB-8065), Anemia G-401 (CRL-1441) Factors VII, VIII, IX Endothelial cells HUV-EC-C(CRL-1730) Hemophilia Famoxin (recombinant gAcrp30) Adipocytes NA² Obesity Fibroblast growth factor (basic) Cerebral cortex, hypothalamus HCN-1A (CRL-10442) Wound healing, angiogenesis Gastric lipase Pancreas BxPC-3 (CRL-1687) Pancreatic insufficiency, cystic fibrosis Glucocerebrosidase Macrophages U-937 (CRL-1593.2) Gaucher disease Granulocyte macrophage-colony T-lymphocytes J.CaM1.6 (CRL-2063) Chemotherapy neutropenia stimulating factor Human growth hormone Pituitary gland HP75 (CRL-2506) Growth retardation, Turner's (somatotropin) syndrome Human serum albumin Liver (hepatocytes) Hep G2 (HB-8065) Blood replacement (surgery, burns) Insulin Pancreas (Islet beta cells) BxPC-3 (CRL-1687) Diabetes Interferons alpha Leukocytes WBC264-9C (HB-8902) Cancer, hepatitis C Interferons beta Fibroblasts WI 38 (CCL-75) Multiple sclerosis Interleukin-2, -4, -10 T-lymphocytes J.CaM1.6 (CRL-2063) Cancer, rheumatoid arthritis, hepatitis Interleukin-18 Monocytes and macrophages U-937 (CRL-1593.2) Cancer, bacterial infections Interleukin-1 Receptor Antagonist Epithelium HBE4-E6/E7 (CRL-2078) Rheumatoid arthritis Soluble Tumor Necrosis Factor Placenta, spleen, fibroblasts BeWo (CCL-98) Rheumatoid arthritis, receptor multiple sclerosis van Willebrand's factor Endothelial cells HUV-EC-C (CRL-1730) Hemophilia ¹These cell lines are offered only as examples of cultured cells corresponding to the tissues and somatic cells; ATCC #: American Type Culture Collection accession number ²NA: Not Available; adipocytes can be differentiated from various other cell types

TABLE-US-00002 TABLE 2 Oligonucleotides used for polymerase chain reactions (PCR primers) or DNA mutagenesis (SEQ ID NOS:134-176) SEQ ID NO: Number Sequence 134 C65 AACAAGCTTGATATCAGATCTGCTAGCTTGGTCGAGC TGATACTTCCC 135 C66 AAACTCGAGCGGCCGCGAATTCGTCGACTTTACCACT CCCTATCAGTGATAGAG 136 C67 AAACCGCGGCATGGAAGACGCCAAAAACATAAAGAAA GG 137 C68 TATGGATCCTAGAATTACACGGCGATCTTTCC 138 C81 AAACCATGGCCGAGTACAAGCCCACGGTGCGCC 139 C82 AAATCTAGATCAGGCACCGGGCTTGCGGGTCATGC 140 C85 CATTTCCCCGAAAAGTGCCACC 141 D30 TCACTGCTAGCGAGTGGTAAACTC 142 D41 GAAGTCGACGAGGCAGGCAGAAGTATGC 143 D42 GAGCCGCGGTTTAGTTCCTCACCTTGTCG 144 D51 TCTGGAAGCTTTGCTGAAGAAAC 145 D58 CCAAGTTGACCAGTGCC 146 D70 TACAAGCCAACCACGGCCT 147 D71 CGGAAGTGCTTGACATTGGG 148 D80 GTTCGTGGACACGACCTCCG 149 D89 GGGCAAGATGTCGTAGTCAGG 150 D90 AGGCCCATGGTCACCTCCATCGCTACTGTG 151 D91 CTAATCACTCACTGTGTAAT 152 D93 AATTACAGGCGCGCC 153 D94 AATTGGCGCGCCTGT 154 D95 TGCTTTGCATACTTCTGCCTGCCTC 155 E12 TAGGGGGGATCCAAATGTTC 156 E13 CCTAAAAGAAGATCTTTAGC 157 E14 AAGTGTTGGATCCACTTTGG 158 E15 TTTGAAGATCTACCAAATGG 159 E16 GTTCGGGATCCACCTGGCCG 160 E17 TAGGCAAGATCTTGGCCCTC 161 E18 CCTCTCTAGGGATCCGACCC 162 E19 CTAGAGAGATCTTCCAGTAT 163 E20 AGAGTTCCGGATCCGCCTGG 164 E21 CCAGGCAGACTCGGAACTCT 165 E22 TGGTGAAACCGGATCCCTAC 166 E23 AGGTCAGGAGATCTAGACCA 167 E25 CCATTTTCGCTTCCTTAGCTCC 168 E42 CGATGTAACCCACTCGTGCACC 169 E57 AGAGATCTAGGATAATTTCG 170 E92 AGGCGCTAGCACGCGTTCTACTCTTTTCCTACTCTG 171 E93 GATCAAGCTTACGCGTCTAAAGGCATTTTATATAG 172 E94 AGGCGCTAGCACGCGTTCAGAGTTAGTGATCCAGG 173 E95 GATCAAGCTTACGCGTCAGTAAAGGTTTCGTATGG 174 E96 AGGCGCTAGCACGCGTTCTACTCTTTCATTACTCTG 175 E97 CGAGGAAGCTGGAGAAGGAGAAGCTG 176 E98 CAAGGGCCGCAGCTTACACATGTTC

TABLE-US-00003 TABLE 3 STAR elements of the invention, including genomic location and length (SEQ ID NOS: 1-66) STAR SEQ ID NO: Location¹ Length 1 1 2q31.1 750 2 2 7p15.2 916 3 3 15q11.2 and 10q22.2 2132 4 4 1p31.1 and 14q24.1 1625 5 5 20q13.32 1571 6 6 2p21 1173 7 7 1q34 2101 8 8 9q32 1839 9 9 10p15.3 1936 10 10 Xp11.3 1167 11 11 2p25.1 1377 12 12 5q35.3 1051 13 13 9q34.3 1291 14 14 22q11.22 732 15 15 1p36.31 1881 16 16 1p21.2 1282 17 17 2q31.1 793 18 18 2q31.3 497 19 19 6p22.1 1840 20 20 8p13.3 780 21 21 6q24.2 620 22 22 2q12.2 1380 23 23 6p22.1 1246 24 24 1q21.2 948 25 25 1q21.3 1067 26 26 1q21.1 540 27 27 1q23.1 1520 28 28 22q11.23 961 29 29 2q13.31 2253 30 30 22q12.3 1851 31 31 9q34.11 and 22q11.21 1165 32 32 21q22.2 771 33 33 21q22.2 1368 34 34 9q34.14 755 35 35 7q22.3 1211 36 36 21q22.2 1712 37 37 22q11.23 1331 38 38 22q11.1 and 22q11.1 ~1000 39 39 22q12.3 2331 40 40 22q11.21 1071 41 41 22q11.21 1144 42 42 22q11.1 735 43 43 14q24.3 1231 44 44 22q11.1 1591 45 45 22q11.21 1991 46 46 22q11.23 1871 47 47 22q11.21 1082 48 48 22q11.22 1242 49 49 Chr 12 random clone, and 1015 3q26.32 50 50 6p21.31 2361 51 51 5q21.3 2289 52 52 7p15.2 1200 53 53 Xp11.3 1431 54 54 4q21.1 981 55 55 15q13.1 501 56 56 includes 3p25.3 741 57 57 4q35.2 1371 58 58 21q11.2 1401 59 59 17 random clone 872 60 60 4p16.1 and 6q27 2068 61 61 7p14.3 and 11q25 1482 62 62 14q24.3 1011 63 63 22q13.3 1421 64 64 17q11.2 1414 65 65 7q21.11 = 28.4 1310 66 66 20q13.33 and 6q14.1 ~2800 ¹Chromosomal location is determined by BLAST search of DNA sequence data from the STAR elements against the human genome database. The location is given according to standard nomenclature referring to the cytogenetic ideogram of each chromosome; e.g., 1p2.3 is the third cytogenetic sub-band of the second cytogenetic band of the short arm of chromosome 1 (WorldWideWeb.ncbi.nlm.nih.gov/Class/MLACourse/Genetics/chrombanding.html- ).F, forward sequencing reaction result; R, reverse sequencing reaction result.

TABLE-US-00004 TABLE 4 STAR elements convey stability over time on transgene expression¹ Cell Divisions² Luciferase Expression³ STAR6 (SEQ ID NO: 6) 42 18,000 plus puromycin 60 23,000 84 20,000 108 16,000 STAR6 (SEQ ID NO: 6) 84 12,000 without puromycin⁴ 108 15,000 144 12,000 ¹Plasmid pSDH-Tet-STAR6 was transfected into U-2 OS cells, and clones were isolated and cultivated in doxycycline-free medium as described in Example 1. Cells were transferred to fresh culture vessels weekly at a dilution of 1:20. ²The number of cell divisions is based on the estimation that in one week the culture reaches cell confluence, which represents ~6 cell divisions. ³Luciferase was assayed as described in Example 1. ⁴After 60 cell divisions the cells were transferred to two culture vessels; one was supplied with culture medium that contained puromycin, as for the first 60 cell divisions, and the second was supplied with culture medium lacking antibiotic.

TABLE-US-00005 TABLE 5 Human STAR elements and their putative mouse orthologs and paralogs NUMBER STAR Human¹ Mouse² Similarity³ SEQ ID NO: 1 1 2q31.1 2D 600 bp 69% 1 2 2 7p15.2 6B3 909 bp 89% 2 3 3a 5q33.3 11B2 248 bp 83% 3 4 3b 10q22.2 14B 1. 363 bp 89% 3 2. 163 bp 86% 5 6 2p21 17E4 437 bp 78% 6 6 12 5q35.3 11b1.3 796 bp 66% 12 7 13 9q34.3 2A3 753 bp 77% 13 8 18 2q31.3 2E1 497 bp 72% 18 9 36 21q22.2 16C4 166 bp 79% 36 10 40 22q11.1 6F1 1. 270 bp 75% 40 2. 309 bp 70% 11 50 6p21.31 17B1 1. 451 bp 72% 50 2. 188 bp 80% 3. 142 bp 64% 12 52 7p15.2 6B3 1. 846 bp 74% 52 2. 195 bp 71% 13 53 Xp11.3 XA2 364 bp 64% 53 14 54 4q21.1 5E3 1. 174 bp 80% 54 2. 240 bp 73% 3. 141 bp 67% 4. 144 bp 68% 15 61a 7p14.3 6B3 188 bp 68% 61 ¹Cytogenetic location of STAR element in the human genome. ²Cytogenetic location of STAR element ortholog in the mouse genome. ³Length of region(s) displaying high sequence similarity, and percentage similarity. In some cases more than one block of high similarity occurs; in those cases, each block is described separately. Similarity <60% is not considered significant.

TABLE-US-00006 TABLE 6 Oligonucleotide patterns (6 base pairs) over-represented in STAR elements. Ob- Ex- Signif- Number Oligo- served pected icance of SEQ Num- nucleotide occur- occur- coef- matching ID ber sequence rences rences ficient STARs NO: 1 CCCCAC 107 49 8.76 51 177 2 CAGCGG 36 9 7.75 23 178 3 GGCCCC 74 31 7.21 34 179 4 CAGCCC 103 50 7.18 37 180 5 GCCCCC 70 29 6.97 34 181 6 CGGGGC 40 12 6.95 18 182 7 CCCCGC 43 13 6.79 22 183 8 CGGCAG 35 9 6.64 18 184 9 AGCCCC 83 38 6.54 40 185 10 CCAGGG 107 54 6.52 43 186 11 GGACCC * 58 23 6.04 35 187 12 GCGGAC 20 3 5.94 14 188 13 CCAGCG 34 10 5.9 24 189 14 GCAGCC 92 45 5.84 43 190 15 CCGGCA 28 7 5.61 16 191 16 AGCGGC 27 7 5.45 17 192 17 CAGGGG 86 43 5.09 43 193 18 CCGCCC 43 15 5.02 18 194 19 CCCCCG 35 11 4.91 20 195 20 GCCGCC 34 10 4.88 18 196 21 GCCGGC 22 5 4.7 16 197 22 CGGACC 19 4 4.68 14 198 23 CGCCCC 35 11 4.64 19 199 24 CGCCAG 28 8 4.31 19 200 25 CGCAGC 29 8 4.29 20 201 26 CAGCCG 32 10 4 24 202 27 CCCACG 33 11 3.97 26 203 28 GCTGCC 78 40 3.9 43 204 29 CCCTCC 106 60 3.87 48 205 30 CCCTGC * 92 50 3.83 42 206 31 CACCCC 77 40 3.75 40 207 32 GCGCCA 30 10 3.58 23 208 33 AGGGGC 70 35 3.55 34 209 34 GAGGGC 66 32 3.5 40 210 35 GCGAAC 14 2 3.37 13 211 36 CCGGCG 17 4 3.33 12 212 37 AGCCGG 34 12 3.29 25 213 38 GGAGCC 67 34 3.27 40 214 39 CCCCAG 103 60 3.23 51 215 40 CCGCTC 24 7 3.19 19 216 41 CCCCTC 81 44 3.19 43 217 42 CACCGC 33 12 3.14 22 218 43 CTGCCC 96 55 3.01 42 219 44 GGGCCA 68 35 2.99 39 220 45 CGCTGC 28 9 2.88 22 221 46 CAGCGC 25 8 2.77 19 222 47 CGGCCC 28 10 2.73 19 223 48 CCGCCG 19 5 2.56 9 224 49 CCCCGG 30 11 2.41 17 225 50 AGCCGC 23 7 2.34 17 226 51 GCACCC 55 27 2.31 38 227 52 AGGACC 54 27 2.22 33 228 53 AGGGCG 24 8 2.2 18 229 54 CAGGGC 81 47 2.18 42 230 55 CCCGCC 45 21 2.15 20 231 56 GCCAGC 66 36 2.09 39 232 57 AGCGCC 21 6 2.09 18 233 58 AGGCCC 64 34 2.08 32 234 59 CCCACC 101 62 2.05 54 235 60 CGCTCA 21 6 2.03 17 236 61 AACGCG 9 1 1.96 9 237 62 GCGGCA 21 7 1.92 14 238 63 AGGTCC 49 24 1.87 36 239 64 CCGTCA 19 6 1.78 14 240 65 CAGAGG 107 68 1.77 47 241 66 CCCGAG 33 14 1.77 22 242 67 CCGAGG 36 16 1.76 25 243 68 CGCGGA 11 2 1.75 8 244 69 CCACCC 87 53 1.71 45 245 70 CCTCGC 23 8 1.71 20 246 71 CAAGCC 59 32 1.69 40 247 72 TCCGCA 18 5 1.68 17 248 73 CGCCGC 18 5 1.67 9 249 74 GGGAAC 55 29 1.63 39 250 75 CCAGAG 93 58 1.57 49 251 76 CGTTCC 19 6 1.53 16 252 77 CGAGGA 23 8 1.5 19 253 78 GGGACC 48 24 1.48 31 254 79 CCGCGA 10 2 1.48 8 255 80 CCTGCG 24 9 1.45 17 256 81 CTGCGC 23 8 1.32 14 257 82 GACCCC 47 24 1.31 33 258 83 GCTCCA 66 38 1.25 39 259 84 CGCCAC 33 15 1.19 21 260 85 GCGGGA 23 9 1.17 18 261 86 CTGCGA 18 6 1.15 15 262 87 CTGCTC 80 49 1.14 50 263 88 CAGACG 23 9 1.13 19 264 89 CGAGAG 21 8 1.09 17 265 90 CGGTGC 18 6 1.06 16 266 91 CTCCCC 84 53 1.05 47 267 92 GCGGCC 22 8 1.04 14 268 93 CGGCGC 14 4 1.04 13 269 94 AAGCCC * 60 34 1.03 42 270 95 CCGCAG 24 9 1.03 17 271 96 GCCCAC 59 34 0.95 35 272 97 CACCCA 92 60 0.93 49 273 98 GCGCCC 27 11 0.93 18 274 99 ACCGGC 15 4 0.92 13 275 100 CTCGCA 16 5 0.89 14 276 101 ACGCTC 16 5 0.88 12 277 102 CTGGAC 58 33 0.88 32 278 103 GCCCCA 67 40 0.87 38 279 104 ACCGTC 15 4 0.86 11 280 105 CCCTCG 21 8 0.8 18 281 106 AGCCCG 22 8 0.79 14 282 107 ACCCGA 16 5 0.78 13 283 108 AGCAGC 79 50 0.75 41 284 109 ACCGCG 14 4 0.69 7 285 110 CGAGGC 29 13 0.69 24 286 111 AGCTGC 70 43 0.64 36 287 112 GGGGAC 49 27 0.64 34 288 113 CCGCAA 16 5 0.64 12 289 114 CGTCGC 8 1 0.62 6 290 115 CGTGAC 17 6 0.57 15 291 116 CGCCCA 33 16 0.56 22 292 117 CTCTGC 97 65 0.54 47 293 118 AGCGGG 21 8 0.52 17 294 119 ACCGCT 15 5 0.5 11 295 120 CCCAGG 133 95 0.49 58 296 121 CCCTCA 71 45 0.49 39 297

122 CCCCCA * 77 49 0.49 42 298 123 GGCGAA 16 5 0.48 14 299 124 CGGCTC 29 13 0.47 19 300 125 CTCGCC 20 8 0.46 17 301 126 CGGAGA 20 8 0.45 14 302 127 TCCCCA 95 64 0.43 52 303 128 GACACC 44 24 0.42 33 304 129 CTCCGA 17 6 0.42 13 305 130 CTCGTC 17 6 0.42 14 306 131 CGACCA 13 4 0.39 11 307 132 ATGACG 17 6 0.37 12 308 133 CCATCG 17 6 0.37 13 309 134 AGGGGA 78 51 0.36 44 310 135 GCTGCA 77 50 0.35 43 311 136 ACCCCA 76 49 0.33 40 312 137 CGGAGC 21 9 0.33 16 313 138 CCTCCG 28 13 0.32 19 314 139 CGGGAC 16 6 0.3 10 315 140 CCTGGA 88 59 0.3 45 316 141 AGGCGA 18 7 0.29 17 317 142 ACCCCT 54 32 0.28 36 318 143 GCTCCC 56 34 0.27 36 319 144 CGTCAC 16 6 0.27 15 320 145 AGCGCA 16 6 0.26 11 321 146 GAAGCC 62 38 0.25 39 322 147 GAGGCC 79 52 0.22 42 323 148 ACCCTC 54 32 0.22 33 324 149 CCCGGC 37 20 0.21 21 325 150 CGAGAA 20 8 0.2 17 326 151 CCACCG 29 14 0.18 20 327 152 ACTTCG 16 6 0.17 14 328 153 GATGAC 48 28 0.17 35 329 154 ACGAGG 23 10 0.16 18 330 155 CCGGAG 20 8 0.15 18 331 156 ACCCAC 60 37 0.12 41 332 157 CTGGGC 105 74 0.11 50 333 158 CCACGG 23 10 0.09 19 334 159 CGGTCC 13 4 0.09 12 335 160 AGCACC * 54 33 0.09 40 336 161 ACACCC 53 32 0.08 38 337 162 AGGGCC 54 33 0.08 30 338 163 CGCGAA 6 1 0.02 6 339 164 GAGCCC 58 36 0.02 36 340 165 CTGAGC 71 46 0.02 45 341 166 AATCGG 13 4 0.02 11 342 The patterns are ranked according to significance coefficient. These were determined using RSA-Tools with the sequence of the human genome as reference. Patterns that comprise the most discriminant variables in Linear Discriminant Analysis are indicated with an asterisk. (SEQ ID NOS:177-342)

TABLE-US-00007 TABLE 7 Dyad patterns over-represented in STAR elements. Signifi- Observed Expected cance occur- occur- coef- SEQ ID Number Dyad sequence rences rences ficient NO 1 CCCN{2}CGG 36 7 9.31 343 2 CCGN{6}CCC 40 10 7.3 344 3 CAGN{0}CGG 36 8 7.13 345 4 CGCN{15}CCC 34 8 6.88 346 5 CGGN{9}GCC 33 7 6.82 347 6 CCCN{9}CGC 35 8 6.72 348 7 CCCN{1}GCG 34 8 6.64 349 8 CCCN{0}CAC 103 48 6.61 350 9 AGCN{16}CCG 29 6 5.96 351 10 CCCN{4}CGC 34 8 5.8 352 11 CGCN{13}GGA 26 5 5.77 353 12 GCGN{16}CCC 30 7 5.74 354 13 CGCN{5}GCA 25 5 5.49 355 14 CCCN{14}CCC 101 49 5.43 356 15 CTGN{4}CGC 34 9 5.41 357 16 CCAN{12}GCG 28 6 5.37 358 17 CGGN{11}CAG 36 10 5.25 359 18 CCCN{5}GCC 75 33 4.87 360 19 GCCN{0}CCC 64 26 4.81 361 20 CGCN{4}GAC 19 3 4.78 362 21 CGGN{0}CAG 33 9 4.76 363 22 CCCN{3}CGC 32 8 4.67 364 23 CGCN{1}GAC 20 3 4.58 365 24 GCGN{2}GCC 29 7 4.54 366 25 CCCN{4}GCC 76 34 4.53 367 26 CCCN{1}CCC 103 52 4.53 368 27 CCGN{13}CAG 33 9 4.5 369 28 GCCN{4}GGA 64 27 4.48 370 29 CCGN{3}GGA 26 6 4.46 371 30 AGGN{2}GGG 118 63 4.44 372 31 CACN{5}GCG 22 4 4.42 373 32 CGCN{17}CCA 27 6 4.39 374 33 CCCN{9}GGC 69 30 4.38 375 34 CCTN{5}GCG 28 7 4.37 376 35 GCGN{0}GAC 19 3 4.32 377 36 GCCN{0}GGC 40 7 4.28 378 37 GCGN{2}CCC 26 6 4.27 379 38 CCGN{11}CCC 32 9 4.17 380 39 CCCN{8}TCG 23 5 4.12 381 40 CCGN{17}GCC 30 8 4.12 382 41 GGGN{5}GGA 101 52 4.11 383 42 GGCN{6}GGA 71 32 4.1 384 43 CCAN{4}CCC 96 48 4.1 385 44 CCTN{14}CCG 32 9 4.09 386 45 GACN{12}GGC 45 16 4.07 387 46 CGCN{13}CCC 30 8 4.04 388 47 CAGN{16}CCC 92 46 4.02 389 48 AGCN{10}GGG 75 35 3.94 390 49 CGGN{13}GGC 30 8 3.93 391 50 CGGN{1}GCC 30 8 3.92 392 51 AGCN{0}GGC 26 6 3.9 393 52 CCCN{16}GGC 64 28 3.89 394 53 GCTN{19}CCC 67 29 3.87 395 54 CCCN{16}GGG 88 31 3.81 396 55 CCCN{9}CGG 30 8 3.77 397 56 CCCN{10}CGG 30 8 3.76 398 57 CCAN{0}GCG 32 9 3.75 399 58 GCCN{17}CGC 26 6 3.74 400 59 CCTN{6}CGC 27 7 3.73 401 60 GGAN{1}CCC 63 27 3.71 402 61 CGCN{18}CAC 24 5 3.7 403 62 CGCN{20}CCG 21 4 3.69 404 63 CCGN{0}GCA 26 6 3.69 405 64 CGCN{20}CCC 28 7 3.69 406 65 AGCN{15}CCC 67 30 3.65 407 66 CCTN{7}GGC 69 31 3.63 408 67 GCCN{5}CGC 32 9 3.61 409 68 GCCN{14}CGC 28 7 3.59 410 69 CAGN{11}CCC 89 45 3.58 411 70 GGGN{16}GAC 53 21 3.57 412 71 CCCN{15}GCG 25 6 3.57 413 72 CCCN{0}CGC 37 12 3.54 414 73 CCCN{16}AGC * 67 30 3.54 415 74 AGGN{9}GGG 96 50 3.52 416 75 CGCN{12}CTC 28 7 3.46 417 76 CACN{8}CGC 23 5 3.43 418 77 CCAN{7}CCG 31 9 3.42 419 78 CGGN{1}GCA 25 6 3.41 420 79 CGCN{14}CCC 29 8 3.4 421 80 AGCN{0}CCC 76 36 3.4 422 81 CGCN{13}GTC 18 3 3.37 423 82 GCGN{3}GCA 26 7 3.35 424 83 CGGN{0}GGC 34 11 3.35 425 84 GCCN{14}CCC 68 31 3.33 426 85 ACCN{7}CGC 21 4 3.32 427 86 AGGN{7}CGG 33 10 3.31 428 87 CCCN{16}CGA 22 5 3.3 429 88 CGCN{6}CAG 31 9 3.29 430 89 CAGN{11}GCG 29 8 3.29 431 90 CCGN{12}CCG 19 4 3.26 432 91 CGCN{18}CAG 27 7 3.24 433 92 CAGN{1}GGG 80 39 3.21 434 93 CGCN{0}CCC 32 10 3.2 435 94 GCGN{18}GCC 26 7 3.18 436 95 CGGN{15}GGC 27 7 3.15 437 96 CCCN{15}AGG 72 34 3.14 438 97 AGGN{20}GCG 26 7 3.14 439 98 CGGN{5}CTC 26 7 3.13 440 99 TCCN{17}CGA 23 5 3.12 441 100 GCGN{4}CCC 30 9 3.08 442 101 CCCN{2}CGC 30 9 3.07 443 102 CGTN{3}CAG 28 8 3.06 444 103 CCGN{13}GAG 27 7 3.05 445 104 CTCN{6}CGC 28 8 3.04 446 105 CGCN{4}GAG 21 5 3.03 447 106 GCGN{5}GGA 24 6 3.03 448 107 CCGN{1}CAG 27 7 3.01 449 108 CGCN{11}CCG 18 3 2.99 450 109 GCGN{19}CCC 26 7 2.98 451 110 CGCN{18}GAA 21 5 2.98 452 111 GGGN{19}GGA 78 39 2.95 453 112 CCAN{1}CGG 24 6 2.94 454 113 CCCN{7}GCG 25 6 2.94 455 114 AGGN{10}CCC 84 43 2.92 456 115 CCAN{0}GGG 97 52 2.88 457 116 CAGN{10}CCC 82 41 2.87 458 117 CCGN{18}CCG 19 4 2.86 459 118 CCGN{18}GGC 26 7 2.85 460 119 CCCN{2}GCG 24 6 2.84 461 120 CGCN{1}GGC 25 7 2.83 462 121 CCGN{5}GAC 19 4 2.81 463

122 GGAN{0}CCC 52 22 2.8 464 123 CCCN{1}CCG 29 9 2.78 465 124 CCCN{15}ACG 23 6 2.75 466 125 AGCN{8}CCC 66 31 2.73 467 126 CCCN{3}GGC 60 27 2.71 468 127 AGGN{9}CGG 31 10 2.7 469 128 CCCN{14}CGC 27 8 2.7 470 129 CCGN{0}CCG 19 4 2.7 471 130 CGCN{8}AGC 23 6 2.69 472 131 CGCN{19}ACC 21 5 2.68 473 132 GCGN{17}GAC 17 3 2.66 474 133 AGCN{1}GCG 24 6 2.63 475 134 CCGN{11}GGC 31 10 2.63 476 135 CGGN{4}AGA 26 7 2.63 477 136 CGCN{14}CCG 17 3 2.62 478 137 CCTN{20}GCG 24 6 2.62 479 138 CCAN{10}CGC 26 7 2.61 480 139 CCCN{20}CAC 69 33 2.6 481 140 CCGN{11}GCC 27 8 2.6 482 141 CGCN{18}CCC 26 7 2.59 483 142 CGGN{15}CGC 16 3 2.57 484 143 CGCN{16}GCC 24 6 2.55 485 144 CGCN{20}GGC 23 6 2.54 486 145 CGCN{19}CCG 18 4 2.52 487 146 CGGN{10}CCA 28 8 2.51 488 147 CGCN{17}CCC 26 7 2.51 489 148 CGCN{11}ACA 23 6 2.51 490 149 CGGN{0}ACC 17 3 2.5 491 150 GCGN{10}GCC 24 6 2.49 492 151 GCGN{8}GAC 17 3 2.49 493 152 CCCN{15}GGG 84 32 2.44 494 153 CGGN{16}GGC 27 8 2.44 495 154 CGCN{16}CCA 23 6 2.42 496 155 GCCN{3}CCC 73 36 2.4 497 156 CAGN{4}GGG 94 51 2.4 498 157 CCCN{6}GCG 23 6 2.38 499 158 CCGN{16}CGC 17 3 2.38 500 159 CCCN{17}GCA 61 28 2.37 501 160 CGCN{13}TCC 24 6 2.37 502 161 GCCN{1}CGC 29 9 2.36 503 162 CCGN{19}GAG 26 7 2.35 504 163 GGGN{10}GGA 89 48 2.35 505 164 CAGN{5}CCG 32 11 2.35 506 165 CGCN{3}AGA 19 4 2.32 507 166 GCCN{0}GCC 29 9 2.32 508 167 CCCN{8}GGC 61 28 2.31 509 168 CCTN{6}GCG 22 6 2.29 510 169 GACN{6}CCC 48 20 2.29 511 170 CGGN{1}CCC 26 8 2.27 512 171 CCCN{15}CCG 30 10 2.27 513 172 CAGN{9}CCC 84 44 2.26 514 173 CGGN{10}GGC 27 8 2.26 515 174 CGAN{10}ACG 10 1 2.26 516 175 GCGN{3}TCC 21 5 2.26 517 176 CCCN{3}GCC 75 38 2.24 518 177 GCGN{1}ACC 17 3 2.24 519 178 CCGN{9}AGG 27 8 2.23 520 179 CGCN{16}CAG 26 8 2.23 521 180 GGCN{0}CCC 62 29 2.22 522 181 AGGN{12}CCG 26 8 2.19 523 182 CCGN{0}GCG 16 3 2.19 524 183 CCGN{2}GCC 30 10 2.18 525 184 CCGN{11}GTC 19 4 2.17 526 185 CAGN{0}CCC 88 47 2.17 527 186 CCCN{5}CCG 32 11 2.17 528 187 GCCN{20}CCC 66 32 2.15 529 188 GACN{2}CGC 18 4 2.14 530 189 CGCN{6}CAC 23 6 2.13 531 190 AGGN{14}GCG 25 7 2.1 532 191 GACN{5}CGC 17 3 2.1 533 192 CCTN{19}CCG 29 9 2.1 534 193 CCGN{12}GGA 24 7 2.08 535 194 GGCN{9}GAC * 44 18 2.08 536 195 AGGN{10}GGG 94 52 2.07 537 196 CCGN{10}GAG 25 7 2.07 538 197 CGCN{6}GGA 20 5 2.06 539 198 CGCN{7}AGC 23 6 2.04 540 199 CCAN{13}CGG 26 8 2.03 541 200 CGGN{6}GGA 25 7 2.03 542 201 CGCN{19}GCC 24 7 2.03 543 202 CCAN{12}CGC 24 7 2.02 544 203 CGGN{1}GGC 41 16 2.02 545 204 GCGN{3}CCA 25 7 2.01 546 205 AGGN{1}CGC 21 5 2 547 206 CTCN{5}CGC 24 7 1.98 548 207 CCCN{0}ACG 30 10 1.97 549 208 CAGN{17}CCG 29 9 1.96 550 209 GGCN{4}CCC 62 30 1.96 551 210 AGGN{8}GCG 26 8 1.96 552 211 CTGN{1}CCC 88 48 1.94 553 212 CCCN{16}CAG 85 46 1.94 554 213 CGCN{9}GAC 16 3 1.93 555 214 CAGN{6}CCG 29 9 1.92 556 215 CGTN{12}CGC 11 1 1.92 557 216 CTCN{7}GCC 69 35 1.92 558 217 CGCN{19}TCC 22 6 1.92 559 218 CCCN{7}GCC 67 33 1.91 560 219 CAGN{13}CGG 30 10 1.9 561 220 CGCN{1}GCC 27 8 1.9 562 221 CGCN{17}CCG 17 4 1.89 563 222 AGGN{4}CCC 63 31 1.89 564 223 AGCN{10}CGC 21 5 1.89 565 224 CCCN{11}CGG 30 10 1.88 566 225 CCCN{8}GCC 75 39 1.86 567 226 CCGN{1}CGG 22 3 1.86 568 227 CCCN{1}ACC 71 36 1.85 569 228 CGCN{0}CAG 25 7 1.85 570 229 CCGN{19}TGC 23 6 1.82 571 230 GCGN{4}CGA 12 2 1.82 572 231 CCGN{19}GCC 30 10 1.82 573 232 CCAN{10}CCC 85 46 1.81 574 233 CAGN{13}GGG 91 51 1.81 575 234 AGCN{18}CGG 23 6 1.81 576 235 CGAN{8}CGC 11 1 1.81 577 236 AGCN{4}CCC 63 31 1.8 578 237 GGAN{6}CCC 61 30 1.8 579 238 CGGN{13}AAG 23 6 1.8 580 239 ACCN{11}CGC 19 5 1.79 581 240 CCGN{12}CAG 28 9 1.78 582 241 CCCN{12}GGG 76 29 1.77 583 242 CACN{17}ACG 22 6 1.76 584 243 CAGN{18}CCC 82 44 1.76 585 244 CGTN{10}GTC 19 5 1.75 586 245 CCCN{13}GCG 23 6 1.75 587 246 GCAN{1}CGC 20 5 1.73 588

247 AGAN{4}CCG 24 7 1.73 589 248 GCGN{10}AGC 22 6 1.72 590 249 CGCN{0}GGA 12 2 1.72 591 250 CGGN{4}GAC 17 4 1.69 592 251 CCCN{12}CGC 26 8 1.68 593 252 GCCN{15}CCC 65 33 1.68 594 253 GCGN{6}TCC 20 5 1.66 595 254 CGGN{3}CAG 33 12 1.65 596 255 CCCN{3}CCA 88 49 1.65 597 256 AGCN{3}CCC 59 28 1.65 598 257 GGGN{16}GCA 65 33 1.65 599 258 AGGN{8}CCG 28 9 1.64 600 259 CCCN{0}CCG 29 10 1.64 601 260 GCGN{5}GAC 16 3 1.64 602 261 CCCN{9}ACC 60 29 1.64 603 262 CTGN{5}CGC 25 8 1.64 604 263 CGCN{14}CTC 23 7 1.64 605 264 CGGN{14}GCA 23 7 1.63 606 265 CCGN{8}GCC 26 8 1.62 607 266 CCGN{7}CAC 23 7 1.62 608 267 AGCN{8}GCG 21 6 1.61 609 268 CGGN{16}GGA 29 10 1.61 610 269 CCAN{12}CCG 26 8 1.61 611 270 CGGN{2}CCC 26 8 1.6 612 271 CCAN{13}GGG 71 37 1.6 613 272 CGGN{15}GCA 21 6 1.6 614 273 CGCN{9}GCA 20 5 1.58 615 274 CGGN{19}CCA 26 8 1.58 616 275 GGGN{15}CGA 20 5 1.57 617 276 CCCN{10}CGC 26 8 1.57 618 277 CTCN{14}CGC 26 8 1.55 619 278 CACN{11}GCG 20 5 1.55 620 279 CCGN{2}GGC 24 7 1.55 621 280 CTGN{18}CCC 85 47 1.54 622 281 GGGN{13}CAC 58 28 1.54 623 282 CCTN{15}GGC 62 31 1.54 624 283 CCCN{20}CGA 20 5 1.54 625 284 CCCN{8}CGA 20 5 1.53 626 285 GAGN{7}CCC 61 30 1.53 627 286 CGCN{2}CCG 22 6 1.53 628 287 CCCN{0}TCC 98 57 1.52 629 288 AGCN{0}GCC 21 6 1.52 630 289 CCCN{2}TCC 82 45 1.52 631 290 CCGN{5}CCC 30 10 1.52 632 291 CGCN{13}CGC 16 3 1.51 633 292 CCCN{1}CGC 28 9 1.51 634 293 GCCN{16}GCA 53 25 1.51 635 294 CCCN{16}CCA 84 46 1.5 636 295 CCGN{13}CGC 19 5 1.5 637 296 CCGN{17}CAG 28 9 1.49 638 297 CGGN{18}GGC 26 8 1.49 639 298 CCGN{14}AGG 23 7 1.49 640 299 CCCN{5}CGG 26 8 1.49 641 300 CCCN{6}GGA 58 28 1.49 642 301 ACGN{2}CCC 20 5 1.49 643 302 CCAN{9}CCG 27 9 1.48 644 303 CCCN{19}CCA 78 42 1.48 645 304 CAGN{0}GGG 77 41 1.48 646 305 AGCN{1}CCC 58 28 1.47 647 306 GCGN{7}TCC 27 9 1.46 648 307 ACGN{18}CCA 25 8 1.46 649 308 GCTN{14}CCC 61 30 1.46 650 309 GCGN{14}CCC 23 7 1.46 651 310 GCGN{19}AGC 20 5 1.45 652 311 CCGN{8}CAG 29 10 1.45 653 312 GCGN{6}GCC 22 6 1.45 654 313 GCGN{10}GCA 20 5 1.44 655 314 CCTN{7}GCC 69 36 1.44 656 315 GCCN{13}GCC 54 26 1.42 657 316 CCCN{14}GCC 63 32 1.42 658 317 CCCN{15}CGG 26 8 1.42 659 318 CCAN{13}CGC 23 7 1.42 660 319 AGCN{11}GGG 67 35 1.41 661 320 GGAN{0}GCC 64 32 1.4 662 321 GCCN{3}TCC 61 30 1.4 663 322 CCTN{5}GCC 69 36 1.39 664 323 CGGN{18}CCC 25 8 1.39 665 324 CCTN{3}GGC 59 29 1.38 666 325 CCGN{0}CTC 22 6 1.38 667 326 AGCN{17}GCG 19 5 1.37 668 327 ACGN{14}GGG 20 5 1.37 669 328 CGAN{12}GGC 19 5 1.37 670 329 CCCN{20}CGC 24 7 1.37 671 330 ACGN{12}CTG 24 7 1.36 672 331 CCGN{0}CCC 36 14 1.36 673 332 CCGN{10}GGA 23 7 1.36 674 333 CCCN{3}GCG 21 6 1.36 675 334 GCGN{14}CGC 22 3 1.35 676 335 CCGN{8}CGC 16 4 1.35 677 336 CGCN{10}ACA 22 6 1.34 678 337 CCCN{19}CCG 28 10 1.33 679 338 CACN{14}CGC 20 5 1.32 680 339 GACN{3}GGC 46 21 1.32 681 340 GAAN{7}CGC 19 5 1.32 682 341 CGCN{16}GGC 21 6 1.31 683 342 GGCN{9}CCC 64 33 1.31 684 343 CCCN{9}GCC 64 33 1.31 685 344 CGCN{0}TGC 26 9 1.3 686 345 CCTN{8}GGC 67 35 1.3 687 346 CCAN{8}CCC 82 46 1.29 688 347 GACN{2}CCC 42 18 1.28 689 348 GGCN{1}CCC 54 26 1.27 690 349 CGCN{0}AGC 24 7 1.26 691 350 AGGN{4}GCG 28 10 1.26 692 351 CGGN{6}TCC 22 6 1.25 693 352 ACGN{19}GGC 20 5 1.25 694 353 CCCN{8}ACG 21 6 1.24 695 354 CCCN{18}GCC 62 31 1.24 696 355 GCCN{2}CGA 19 5 1.24 697 356 CCCN{8}GCG 28 10 1.23 698 357 CCCN{0}CTC 76 41 1.23 699 358 GCCN{11}CGC 27 9 1.22 700 359 AGCN{9}CCC 59 29 1.22 701 360 GCTN{0}GCC 71 38 1.21 702 361 CGCN{3}CCC 26 9 1.21 703 362 CCCN{2}CCC 117 72 1.19 704 363 GCCN{9}CGC 23 7 1.19 705 364 GCAN{19}CGC 19 5 1.19 706 365 CAGN{4}CGG 32 12 1.18 707 366 CAGN{2}GGG 80 44 1.17 708 367 GCCN{16}CCC 67 35 1.16 709 368 GAGN{5}CCC 60 30 1.16 710 369 CCTN{16}TCG 20 6 1.16 711 370 CCCN{2}GGC 62 32 1.15 712 371 GCGN{13}GGA 24 8 1.15 713 372 GCCN{17}GGC 66 25 1.15 714

373 CCCN{14}GGC 58 29 1.14 715 374 AGGN{3}CCG 31 12 1.14 716 375 CACN{0}CGC 32 12 1.14 717 376 CGGN{18}CAG 28 10 1.14 718 377 AGCN{1}GCC 57 28 1.13 719 378 CGCN{18}GGC 23 7 1.13 720 379 CCCN{5}AGG 64 33 1.11 721 380 AACN{0}GCG 9 1 1.11 722 381 CCCN{10}CCA 88 50 1.09 723 382 CGCN{13}GAG 20 6 1.09 724 383 CGCN{7}GCC 25 8 1.08 725 384 CCCN{9}CCG 28 10 1.07 726 385 CGCN{16}CCC 24 8 1.05 727 386 GAAN{13}CGC 18 5 1.05 728 387 GGCN{3}CCC 49 23 1.03 729 388 TCCN{11}CCA 87 50 1.03 730 389 CACN{0}CCC 70 38 1.02 731 390 CGCN{16}CCG 15 3 1.02 732 391 CGGN{15}AGC 21 6 1.02 733 392 CCCN{12}GCG 21 6 1.02 734 393 CCCN{9}GAG 59 30 1.01 735 394 CCGN{20}TCC 24 8 1.01 736 395 CGCN{0}CGC 17 4 1.01 737 396 ATGN{7}CGG 20 6 1 738 397 GGGN{20}GCA 59 30 1 739 398 CGGN{4}GGC 26 9 0.99 740 399 CGGN{16}AGC 22 7 0.99 741 400 CGGN{5}GGC 25 8 0.99 742 401 GCGN{0}GGA 25 8 0.98 743 402 GGCN{20}CAC 52 25 0.98 744 403 CCCN{9}CCC 97 58 0.97 745 404 ACCN{17}GGC 44 20 0.97 746 405 CCCN{6}CGA 18 5 0.96 747 406 AAGN{10}CGG 26 9 0.96 748 407 CGCN{17}CAC 21 6 0.95 749 408 CCCN{16}CGG 25 8 0.94 750 409 GACN{18}GGC 39 17 0.94 751 410 GGGN{15}GAC 47 22 0.92 752 411 GCCN{4}TCC 66 35 0.92 753 412 GGCN{15}CCC 56 28 0.92 754 413 CAGN{12}CGC 24 8 0.92 755 414 CCAN{3}GCG 22 7 0.91 756 415 CCGN{16}GAG 22 7 0.9 757 416 AGCN{2}CGC 24 8 0.89 758 417 GAGN{4}CCC 54 27 0.89 759 418 AGGN{3}CGC 23 7 0.88 760 419 CACN{13}AGG * 67 36 0.88 761 420 CCCN{4}CAG 88 51 0.88 762 421 CCCN{2}GAA 63 33 0.87 763 422 CGCN{19}GAG 21 6 0.87 764 423 ACGN{18}GGG 21 6 0.87 765 424 CCCN{4}GGC 62 32 0.87 766 425 CGGN{9}GAG 28 10 0.86 767 426 CCCN{3}GGG 66 26 0.86 768 427 GAGN{4}GGC 66 35 0.85 769 428 CGCN{5}GAG 18 5 0.84 770 429 CCGN{20}AGG 24 8 0.84 771 430 CCCN{15}CCC 88 51 0.83 772 431 AGGN{17}CCG 25 8 0.82 773 432 AGGN{6}GGG 89 52 0.82 774 433 GGCN{20}CCC 57 29 0.82 775 434 GCAN{17}CGC 19 5 0.82 776 435 CGAN{11}ACG 9 1 0.81 777 436 CGCN{2}GGA 19 5 0.81 778 437 CTGN{5}CCC 79 45 0.8 779 438 TCCN{20}CCA 77 43 0.8 780 439 CCAN{2}GGG 59 30 0.8 781 440 CCGN{15}GCG 14 3 0.8 782 441 CCAN{5}GGG 69 38 0.79 783 442 CGGN{1}TGC 24 8 0.79 784 443 CCCN{14}GCG 21 6 0.79 785 444 CAGN{0}CCG 27 10 0.79 786 445 GCCN{9}TCC 60 31 0.78 787 446 AGGN{20}CGC 22 7 0.78 788 447 CCCN{6}GAC 42 19 0.77 789 448 CGGN{11}CCA 23 7 0.76 790 449 GGGN{14}CAC 57 29 0.75 791 450 GCAN{15}CGC 19 5 0.74 792 451 CGCN{2}ACA 20 6 0.74 793 452 ACCN{9}CCC 57 29 0.73 794 453 GCGN{9}CGC 20 3 0.73 795 454 CAGN{15}GCG 23 7 0.73 796 455 CCCN{18}GTC 45 21 0.72 797 456 GCGN{3}CCC 24 8 0.72 798 457 CGGN{11}GCC 23 8 0.72 799 458 CCCN{1}CGG 24 8 0.71 800 459 GCCN{4}CCA 70 38 0.71 801 460 CCCN{4}CCG 30 12 0.7 802 461 CGTN{2}GCA 21 6 0.7 803 462 AGCN{7}TCG 18 5 0.69 804 463 CCGN{15}GAA 20 6 0.69 805 464 ACCN{5}CCC 62 33 0.69 806 465 CGCN{14}GAG 19 5 0.68 807 466 CCCN{7}CGC 30 12 0.68 808 467 GAGN{12}CGC 21 6 0.68 809 468 GGCN{17}CCC 58 30 0.67 810 469 ACGN{11}CTC 21 7 0.65 811 470 ACAN{9}CGG 24 8 0.65 812 471 CTGN{7}CCC 82 47 0.65 813 472 CCCN{2}GCC 72 40 0.65 814 473 CGGN{2}GCA 24 8 0.64 815 474 CCCN{0}TGC 83 48 0.64 816 475 CGCN{7}ACC 18 5 0.63 817 476 GCAN{2}GCC 54 27 0.63 818 477 GCGN{8}CCA 20 6 0.63 819 478 AGCN{0}CGC 22 7 0.63 820 479 GCGN{2}GCA 18 5 0.63 821 480 CCGN{2}GTC 18 5 0.62 822 481 CCGN{3}ACA 21 7 0.62 823 482 ACGN{13}TGG 21 7 0.62 824 483 CCAN{8}CGC 23 8 0.62 825 484 CCGN{9}GGC 23 8 0.61 826 485 CCAN{5}CCG 25 9 0.61 827 486 AGGN{3}GGG 97 59 0.61 828 487 CAGN{2}GGC 78 45 0.61 829 488 CCCN{8}CAG 81 47 0.61 830 489 AGCN{5}CAG 80 46 0.6 831 490 CGGN{16}GCC 22 7 0.6 832 491 GCGN{15}CCC 23 8 0.6 833 492 CCCN{11}GCC 59 31 0.59 834 493 CGAN{2}ACG 9 1 0.59 835 494 CGGN{4}GCC 22 7 0.59 836 495 CACN{6}CGC 19 6 0.59 837 496 CGGN{5}ACG 11 2 0.59 838 497 CTGN{4}GCC * 66 36 0.59 839

498 GGGN{18}CGA 18 5 0.59 840 499 CCTN{8}CGC 22 7 0.59 841 500 GCCN{4}CCC 67 37 0.58 842 501 CGGN{10}GCC 22 7 0.58 843 502 GCCN{5}GGA 54 27 0.57 844 503 ACCN{7}GCG 15 4 0.57 845 504 CCCN{8}CGC 24 8 0.57 846 505 CAGN{5}CCC 77 44 0.56 847 506 CACN{14}GGA 63 34 0.56 848 507 CCCN{1}GCC 94 57 0.55 849 508 CCCN{5}AGC 67 37 0.55 850 509 GGCN{5}GGA 59 31 0.55 851 510 CGAN{17}GAG 19 6 0.55 852 511 CGCN{7}ACA 18 5 0.54 853 512 CCAN{13}CCC 87 52 0.54 854 513 CGGN{20}GGC 24 8 0.54 855 514 CCCN{17}GCC 58 30 0.53 856 515 CCTN{10}CCG 30 12 0.53 857 516 CCCN{8}CCG 27 10 0.53 858 517 CGCN{3}GAG 18 5 0.52 859 518 CGCN{7}AAG 17 5 0.51 860 519 CGGN{11}GGA 23 8 0.51 861 520 CCGN{15}CCG 15 4 0.51 862 521 CCCN{3}GCA 57 30 0.51 863 522 CGGN{2}CAG 24 8 0.5 864 523 AGGN{2}CCG 24 8 0.5 865 524 CCCN{4}CAC 69 38 0.5 866 525 GGAN{19}CCC 56 29 0.49 867 526 CCCN{8}CAC 68 38 0.49 868 527 ACCN{6}CCG 18 5 0.49 869 528 CCCN{6}GGC 54 28 0.49 870 529 CCCN{6}CCG 29 11 0.48 871 530 CGCN{14}GCC 26 9 0.47 872 531 CCGN{5}TCC 25 9 0.46 873 532 GCCN{6}GCC 55 28 0.46 874 533 CGGN{7}GGA 24 8 0.45 875 534 GGGN{6}GGA 87 52 0.44 876 535 GCCN{12}TCC 60 32 0.44 877 536 AGTN{16}CCG 17 5 0.44 878 537 GGCN{19}GCC 68 29 0.44 879 538 CCGN{3}CCG 22 7 0.44 880 539 CCCN{8}ACC 58 31 0.44 881 540 CAGN{15}GCC 77 44 0.44 882 541 CCCN{17}CGG 24 8 0.44 883 542 GCGN{1}CCA 22 7 0.44 884 543 CCCN{14}CAG 79 46 0.44 885 544 CCCN{8}CCC 89 53 0.44 886 545 ACAN{12}GCG 23 8 0.43 887 546 AGGN{4}CCG 23 8 0.43 888 547 CGCN{13}GCC 23 8 0.43 889 548 GAGN{2}CGC 23 8 0.42 890 549 CCCN{9}GCG 21 7 0.42 891 550 CGCN{17}ACA 17 5 0.42 892 551 GCGN{17}CCA 23 8 0.42 893 552 AAGN{18}CCG 20 6 0.42 894 553 CGCN{1}GGA 18 5 0.41 895 554 CCAN{1}CCC 90 54 0.41 896 555 CGTN{18}TGC 20 6 0.41 897 556 TCCN{14}CGA 17 5 0.41 898 557 CACN{5}GGG 56 29 0.4 899 558 CCGN{12}GCA 21 7 0.4 900 559 CTGN{6}CCC 77 44 0.4 901 560 CGGN{8}GGC 32 13 0.4 902 561 CCAN{11}GGG 68 38 0.4 903 562 ACGN{19}CAA 21 7 0.39 904 563 GGGN{20}CCC 72 31 0.39 905 564 CGCN{3}CAG 23 8 0.39 906 565 AGCN{17}GGG 58 31 0.37 907 566 CACN{20}CCG 21 7 0.37 908 567 ACGN{17}CAG 24 8 0.37 909 568 AGGN{1}CCC 60 32 0.37 910 569 CGTN{12}CAC 20 6 0.37 911 570 CGGN{9}GGC 23 8 0.37 912 571 CGCN{10}GCG 18 3 0.37 913 572 CCCN{6}CTC 80 47 0.36 914 573 CCGN{10}AGG 23 8 0.36 915 574 CCCN{18}CAG 79 46 0.36 916 575 AGCN{17}CCG 21 7 0.36 917 576 AGCN{9}GCG 18 5 0.36 918 577 CCAN{3}GGC 62 34 0.36 919 578 CCCN{11}GGC 57 30 0.35 920 579 ACGN{5}GCA 23 8 0.35 921 580 CCCN{14}CGG 23 8 0.35 922 581 CCCN{5}CCA 91 55 0.35 923 582 CCGN{1}AGG 22 7 0.34 924 583 GGGN{10}GAC 45 22 0.34 925 584 CGCN{15}CCA 20 6 0.34 926 585 CCTN{19}CGC 22 7 0.34 927 586 CGTN{3}CGC 10 2 0.33 928 587 AGCN{14}CCG 21 7 0.33 929 588 GGCN{2}CGA 17 5 0.33 930 589 CAGN{8}CCC 79 46 0.33 931 590 CCGN{2}GAC 16 4 0.33 932 591 AGCN{19}AGG 70 40 0.32 933 592 CCTN{4}GGC 64 35 0.32 934 593 CCGN{11}AGC 22 7 0.32 935 594 CACN{4}CGC 18 5 0.32 936 595 CCGN{1}CCC 30 12 0.31 937 596 CTGN{13}GGC 73 42 0.31 938 597 CGCN{16}ACC 15 4 0.31 939 598 CACN{18}CAG 79 46 0.31 940 599 GGCN{8}GCC 68 29 0.29 941 600 GGGN{15}GGA 78 46 0.29 942 601 CCGN{16}GCC 22 7 0.29 943 602 CCGN{20}ACC 18 5 0.29 944 603 CGAN{7}CCC 17 5 0.28 945 604 CCGN{6}CTC 23 8 0.28 946 605 CGGN{10}CTC 22 7 0.28 947 606 CAGN{16}CGC 23 8 0.28 948 607 CCAN{3}AGG 77 45 0.27 949 608 GCCN{18}GCC 52 27 0.27 950 609 CGCN{18}GGA 19 6 0.26 951 610 CCGN{20}GGC 22 7 0.26 952 611 ACAN{1O}GCG 17 5 0.26 953 612 CGGN{5}CCC 25 9 0.25 954 613 CCCN{7}TCC 75 43 0.25 955 614 ACGN{10}CGC 10 2 0.25 956 615 CCCN{3}TCC 81 48 0.25 957 616 CCGN{8}CGG 20 3 0.24 958 617 CCAN{15}CGG 22 7 0.24 959 618 CCGN{6}CCG 17 5 0.24 960 619 CAGN{3}GCG 25 9 0.24 961 620 GAGN{1}CCC 62 34 0.24 962 621 CCGN{18}TGC 22 7 0.23 963 622 CCCN{7}CCA 85 51 0.23 964 623 CGGN{3}CCA 24 9 0.23 965

624 ACGN{1}CCC 18 5 0.23 966 625 CGGN{13}TGA 21 7 0.22 967 626 CTCN{6}GGC 53 28 0.22 968 627 GCGN{2}GAC 15 4 0.22 969 628 GGGN{11}ACC 49 25 0.22 970 629 CGCN{4}GGA 17 5 0.22 971 630 CCCN{11}CCG 27 10 0.22 972 631 CCGN{19}GCA 20 6 0.22 973 632 GCGN{0}GCA 20 6 0.21 974 633 AGAN{7}CCC 61 33 0.21 975 634 CGGN{2}CCA 21 7 0.21 976 635 CCCN{7}CCC 89 54 0.21 977 636 ACCN{4}GCG 15 4 0.2 978 637 CCTN{15}CGC 20 6 0.2 979 638 AGCN{9}GTC 44 21 0.2 980 639 CCCN{18}CTC 74 43 0.2 981 640 CGCN{18}CGA 9 1 0.19 982 641 CCCN{15}GCC 62 34 0.18 983 642 ACCN{11}GGC 45 22 0.18 984 643 AGGN{15}CGC 29 12 0.18 985 644 GCGN{0}CCA 27 10 0.18 986 645 GCGN{9}AGC 18 5 0.17 987 646 GGGN{18}GCA 59 32 0.17 988 647 CCCN{17}CAG 77 45 0.17 989 648 CCAN{8}CGG 22 8 0.16 990 649 CCGN{10}GGC 21 7 0.16 991 650 GCAN{0}GCC 76 44 0.16 992 651 CAGN{2}CGC 20 6 0.16 993 652 CGCN{8}GGC 19 6 0.16 994 653 CTGN{17}GGC 65 36 0.16 995 654 GGGN{14}ACC 46 23 0.16 996 655 CCGN{1}TGC 20 6 0.16 997 656 CAGN{8}CGC 22 8 0.15 998 657 AAGN{11}CGC 17 5 0.15 999 658 CCGN{6}TCC 22 8 0.14 1000 659 CCAN{18}CCC 72 42 0.14 1001 660 CCAN{0}CCC 84 51 0.14 1002 661 GAGN{6}CCC 53 28 0.14 1003 662 AGCN{20}GGC 52 27 0.14 1004 663 CAGN{0}CGC 21 7 0.14 1005 664 CCGN{12}CTC 22 8 0.14 1006 665 CGCN{15}ACG 9 1 0.13 1007 666 GGCN{17}CGA 15 4 0.13 1008 667 CCGN{16}AAG 19 6 0.13 1009 668 CGCN{14}TCC 19 6 0.12 1010 669 AGGN{7}CGC 20 7 0.12 1011 670 CGGN{7}CCC 22 8 0.12 1012 671 CGCN{4}GCC 34 15 0.12 1013 672 CGAN{6}CCC 17 5 0.12 1014 673 CCCN{19}GGA 60 33 0.11 1015 674 CCCN{16}GCG 28 11 0.11 1016 675 CCAN{7}CGC 20 7 0.11 1017 676 CCCN{6}GCC 80 48 0.11 1018 677 GCCN{14}TCC 55 29 0.11 1019 678 AGGN{14}GCC 64 36 0.1 1020 679 CGCN{11}GCC 20 7 0.1 1021 680 TCCN{0}GCA 17 5 0.09 1022 681 GCGN{8}CCC 27 11 0.09 1023 682 CCAN{11}GCG 19 6 0.09 1024 683 CACN{4}GGG 51 26 0.09 1025 684 CGGN{7}TCC 20 7 0.09 1026 685 GCGN{5}GCC 20 7 0.09 1027 686 ACGN{12}CAG 26 10 0.09 1028 687 CCGN{19}CGC 14 4 0.08 1029 688 CGGN{8}TGC 18 5 0.08 1030 689 CCCN{1}GAG 65 37 0.07 1031 690 GCGN{19}TGA 18 6 0.07 1032 691 GGCN{15}GCC 70 31 0.07 1033 692 CCGN{7}CCC 27 11 0.07 1034 693 ACAN{19}CCC 63 35 0.07 1035 694 ACCN{16}GGG 47 24 0.07 1036 695 AGAN{1}GGC 64 36 0.07 1037 696 GGGN{17}TGA 64 36 0.06 1038 697 CAGN{5}GGG 83 50 0.06 1039 698 GCCN{13}CGC 22 8 0.06 1040 699 GCGN{7}GGA 19 6 0.06 1041 700 CAGN{14}CCA 94 58 0.06 1042 701 CCGN{4}GTC 16 4 0.06 1043 702 CCCN{13}CGC 22 8 0.06 1044 703 GCGN{14}ACC 15 4 0.05 1045 704 CAGN{20}GGG 81 49 0.05 1046 705 CCGN{4}CCC 27 11 0.05 1047 706 CGCN{5}GGC 18 6 0.05 1048 707 CCTN{6}GGC 57 31 0.05 1049 708 AGGN{3}GGC 67 38 0.05 1050 709 CGGN{11}CGC 14 4 0.05 1051 710 CTGN{18}GGA 77 46 0.04 1052 711 CACN{17}CCA 74 43 0.04 1053 712 CGGN{3}GAG 22 8 0.04 1054 713 CCCN{9}CCA 82 49 0.03 1055 714 CCCN{1}ACG 18 6 0.03 1056 715 CAGN{1}GCC 72 42 0.03 1057 716 AGGN{6}CCG 23 8 0.03 1058 717 AGCN{9}GGG 57 31 0.03 1059 718 CCCN{7}GGC 54 29 0.02 1060 719 CCTN{13}CCC 88 54 0.02 1061 720 CCGN{19}TTC 20 7 0.02 1062 721 CCCN{7}CCG 27 11 0.02 1063 722 CGAN{6}GGC 17 5 0.01 1064 723 CGGN{4}CTC 21 7 0.01 1065 724 CGGN{0}CGC 13 3 0.01 1066 725 CCTN{13}ACG 19 6 0.01 1067 726 GGGN{6}CAC 53 28 0.01 1068 727 CCCN{16}CGC 21 7 0.01 1069 728 CCCN{10}CTC 76 45 0 1070 729 CCCN{0}CAG 92 57 0 1071 730 GCCN{5}CCC 65 37 0 1072 The patterns are ranked according to significance coefficient. These were determined using RSA-Tools with the random sequence from the human genome as reference. Patterns that comprise the most discriminant variables in Linear Discriminant Analysis are indicated with an asterisk. (SEQ ID NOS:343-1072)

TABLE-US-00008 TABLE 8 Candidate STAR elements tested by Linear Discriminant Analysis SEQ ID NO: Candidate STAR Location¹ Length 66 T2 F 20q13.33 ~2800 67 T2 R 6q14.1 ~2800 68 T3 F 15q12 ~2900 69 T3 R 7q31.2 ~2900 70 T5 F 9q34.13 .sup. ND² 71 T5 R 9q34.13 ND 72 T7 22q12.3 ~1200 73 T9 F 21q22.2 ~1600 74 T9 R 22q11.22 ~1600 75 T10 F 7q22.2 ~1300 76 T10 R 6q14.1 ~1300 77 T11 F 17q23.3 ~2000 78 T11 R 16q23.1 ~2000 79 T12 4p15.1 ~2100 80 T13 F 20p13 ~1700 81 T13 R 1p13.3 ~1700 82 T14 R 11q25 ~1500 83 T17 2q31.3 ND 84 T18 2q31.1 ND ¹Chromosomal location is determined by BLAT search of DNA sequence data from the STAR elements against the human genome database. The location is given according to standard nomenclature referring to the cytogenetic ideogram of each chromosome; e.g., 1p2.3 is the third cytogenetic sub-band of the second cytogenetic band of the short arm of chromosome 1 (WorldWideWeb.ncbi.nlm.nih.gov/Class/MLACourse/Genetics/chrombanding.html- ).F, forward sequencing reaction result; R, reverse sequencing reaction result. When the forward and reverse sequencing results mapped to different genomic locations, each sequence was extended to the full length of the original clone (as determined by restriction mapping) based on sequence information from the human genome database. ²ND: Not Determined.

TABLE-US-00009 TABLE 9 Arabidopsis STAR elements of the invention, including chromosome location and length (SEQ ID NOS: 85-119) STAR Chromosome Length, kb SEQ ID NO: A1 I 1.2 85 A2 I 0.9 86 A3 I 0.9 87 A4 I 0.8 88 A5 I 1.3 89 A6 I 1.4 90 A7 II 1.2 91 A8 II 0.8 92 A9 II 0.9 93 A10 II 1.7 94 A11 II 1.9 95 A12 II 1.4 96 A13 II 1.2 97 A14 II 2.1 98 A15 II 1.4 99 A16 II 0.7 100 A17 II 1.5 101 A18 III 1.5 102 A19 III 0.7 103 A20 III 2.0 104 A21 IV 1.8 105 A22 IV 0.8 106 A23 IV 0.6 107 A24 IV 0.5 108 A25 V 0.9 109 A26 V 1.9 110 A27 V 1.1 111 A28 V 1.6 112 A29 V 0.9 113 A30 V 2.0 114 A31 V 2.0 115 A32 V 1.3 116 A33 V 0.9 117 A34 I 0.9 118 A35 II 1.1 119

REFERENCES

[0230]Altschul S. F., Gish W., Miller W., Myers E. W. and Lipman D. J. (1990) Basic local alignment search tool. J. Mol. Biol. 215, 403-10. [0231]Bell A. C., West A. G. and Felsenfeld G. (2001) Insulators and boundaries: versatile regulatory elements in the eukaryotic genome. Science 291, 447-50. [0232]Berger J., Hauber J., Hauber R., Geiger R. and Cullen B. R. (1988) Secreted placental alkaline phosphatase: a powerful new quantitative indicator of gene expression in eukaryotic cells. Gene 66, 1-10. [0233]Bevan M., Mayer K., White O., Eisen J. A., Preuss D., Bureau T., Salzberg S. L. and Mewes H. W. (2001) Sequence and analysis of the Arabidopsis genome. Curr. Opin. Plant Biol. 4, 105-10. [0234]Bibel M. and Barde Y. A. (2000) Neurotrophins: key regulators of cell fate and cell shape in the vertebrate nervous system. Genes Dev. 14, 2919-37. [0235]Boivin A. and Dura J. M. (1998) In vivo chromatin accessibility correlates with gene silencing in Drosophila. Genetics 150, 1539-49. [0236]Boshart M., Weber F., Jahn G., Dorsch-Hasler K., Fleckenstein B. and Schaffner W. (1985) A very strong enhancer is located upstream of an immediate early gene of human cytomegalovirus. Cell 41, 521-30. [0237]Bunker C. A. and Kingston R. E. (1994) Transcriptional repression by Drosophila and mammalian Polycomb group proteins in transfected mammalian cells. Mol. Cell. Biol. 14, 1721-32. [0238]Chung J. H, Whiteley M. and Felsenfeld G. (1993) A 5' element of the chicken beta-globin domain serves as an insulator in human erythroid cells and protects against position effect in Drosophila. Cell 74, 505-14. [0239]Deuschle U., Meyer W. K. and Thiesen H. J. (1995) Tetracycline-reversible silencing of eukaryotic promoters. Mol. Cell. Biol. 15, 1907-14. [0240]Doll R. F., Crandall J. E., Dyer C. A., Aucoin J. M. and Smith F. I. (1996) Comparison of promoter strengths on gene delivery into mammalian brain cells using AAV vectors. Gene Ther. 3, 437-447. [0241]Foecking M. K. and Hofstetter H. (1986) Powerful and versatile enhancer-promoter unit for mammalian expression vectors. Gene 45, 101-5. [0242]Garrick D., Fiering S., Martin D. I. and Whitelaw E. (1998) Repeat-induced gene silencing in mammals. Nat. Genet. 18, 56-9. [0243]Gerasimova T. I. and Corces V. G. (2001) Chromatin insulators and boundaries: effects on transcription and nuclear organization. Annu. Rev. Genet. 35, 193-208. [0244]Gossen M. and Bujard H. (1992) Tight control of gene expression in mammalian cells by tetracycline-responsive promoters. Proc. Natl. Acad. Sci. U.S.A. 89, 5547-51. [0245]Graham F. L. and van der Eb A. J. (1973) Transformation of rat cells by DNA of human adenovirus 5. Virology 54, 536-9. [0246]Henthorn P., Zervos P., Raducha M., Harris H. and Kadesch T. (1988) Expression of a human placental alkaline phosphatase gene in transfected cells: use as a reporter for studies of gene expression. Proc. Natl. Acad. Sci. U.S.A. 85, 6342-6. [0247]Himes S. R. and Shannon M. F. (2000) Assays for transcriptional activity based on the luciferase reporter gene. Methods Mol. Biol. 130, 165-74. [0248]Huberty C. J. (1994) Applied discriminant analysis, Wiley and Sons, New York. [0249]Initiative A. G. (2000) Analysis of the genome sequence of the flowering plant Arabidopsis thaliana. Nature 408, 796-815. [0250]Izumi M. and Gilbert D. M. (1999) Homogeneous tetracycline-regulatable gene expression in mammalian fibroblasts. J. Cell. Biochem. 76, 280-9. [0251]Kain S. R. (1997) Use of secreted alkaline phosphatase as a reporter of gene expression in mammalian cells. Methods Mol. Biol. 63, 49-60. [0252]Kaufman R. J. (1990) Selection and coamplification of heterologous genes in mammalian cells. Methods in Enzymology 185, 536-566. [0253]Kellum R. and Schedl P. (1992) A group of scs elements function as domain boundaries in an enhancer-blocking assay. Mol. Cell. Biol. 12, 2424-2431. [0254]Kent W. J. (2002) BLAT--the BLAST-like alignment tool. Genome Res. 12, 656-64. [0255]Knofler M., Meinhardt G., Bauer S., Loregger T., Vasicek R., Bloor D. J., Kimber S. J. and Husslein P. (2002) Human Hand1 basic helix-loop-helix (bHLH) protein: extra-embryonic expression pattern, interaction partners and identification of its transcriptional repressor domains. Biochem J. 361, 641-51. [0256]Meyer P. (2000) Transcriptional transgene silencing and chromatin components. Plant Mol. Biol. 43, 221-34. [0257]Mercenier A., Wiedermann U. and Breiteneder H. (2001) Edible genetically modified microorganisms and plants for improved health. Curr. Opin. Biotechnol. 12, 510-5. [0258]Morgenstern J. P. and Land H. (1990) Advanced mammalian gene transfer: high titre retroviral vectors with multiple drug selection markers and a complementary helper-free packaging cell line. Nucleic Acids Res. 18, 3587-96. [0259]Sambrook J., Fritsch E. F. and Maniatis T. (1989) Molecular Cloning: A Laboratory Manual, Second ed., Cold Spring Harbor Laboratory Press, Plainview N.Y. [0260]Sanger F., Nicklen S, and Coulson A. R. (1977) DNA sequencing with chain-terminating inhibitors. Proc. Natl. Acad. Sci. U.S.A. 74, 5463-7. [0261]Stam M., Viterbo A., Mol. J. N. and Kooter J. M. (1998) Position-dependent methylation and transcriptional silencing of transgenes in inverted T-DNA repeats: implications for posttranscriptional silencing of homologous host genes in plants. Mol. Cell. Biol. 18, 6165-77. [0262]Umana P., Jean-Mairet J. and Bailey J. E. (1999) Tetracycline-regulated overexpression of glycosyltransferases in Chinese hamster ovary cells. Biotechnol. Bioeng. 65, 542-9. [0263]Van der Vlag J., den Blaauwen J. L., Sewalt R. G., van Driel R. and Otte A. P. (2000) Transcriptional repression mediated by polycomb group proteins and other chromatin-associated repressors is selectively blocked by insulators. J. Biol. Chem. 275, 697-704. [0264]van Helden J., Andre B. and Collado-Vides J. (1998) Extracting regulatory sites from the upstream region of yeast genes by computational analysis of oligonucleotide frequencies J. Mol. Biol. 281, 827-42. [0265]van Helden J., Andre B. and Collado-Vides J. (2000) A web site for the computational analysis of yeast regulatory sequences. Yeast 16, 177-87. [0266]van Helden J., Rios A. F. and Collado-Vides J. (2000) Discovering regulatory elements in non-coding sequences by analysis of spaced dyads. Nucleic Acids Res. 28, 1808-18. [0267]Vance V. and Vaucheret H. (2001) RNA silencing in plants--defense and counterdefense. Science 292, 2277-80. [0268]Wigler M., Pellicer A., Silverstein S, and Axel R. (1978) Biochemical transfer of single-copy eucaryotic genes using total cellular DNA as donor. Cell 14, 725-31. [0269]Yang T. T., Sinai P., Kitts P. A. and Kain S. R. (1997) Quantification of gene expression with a secreted alkaline phosphatase reporter system. Biotechniques 23, 1110-4. [0270]Zink D. and Paro R. (1995) Drosophila Polycomb-group regulated chromatin inhibits the accessibility of a trans-activator to its target DNA. Embo. J. 14, 5660-71.

Sequence CWU 1

10721749DNAArtificial Sequencesequence of STAR1 1atgcggtggg ggcgcgccag agactcgtgg gatccttggc ttggatgttt ggatctttct 60gagttgcctg tgccgcgaaa gacaggtaca tttctgatta ggcctgtgaa gcctcctgga 120ggaccatctc attaagacga tggtattgga gggagagtca cagaaagaac tgtggcccct 180ccctcactgc aaaacggaag tgattttatt ttaatgggag ttggaatatg tgagggctgc 240aggaaccagt ctccctcctt cttggttgga aaagctgggg ctggcctcag agacaggttt 300tttggccccg ctgggctggg cagtctagtc gaccctttgt agactgtgca cacccctaga 360agagcaacta cccctataca ccaggctggc tcaagtgaaa ggggctctgg gctccagtct 420ggaaaatctg gtgtcctggg gacctctggt cttgcttctc tcctcccctg cactggctct 480gggtgcttat ctctgcagaa gcttctcgct agcaaaccca cattcagcgc cctgtagctg 540aacacagcac aaaaagccct agagatcaaa agcattagta tgggcagttg agcgggaggt 600gaatatttaa cgcttttgtt catcaataac tcgttggctt tgacctgtct gaacaagtcg 660agcaataagg tgaaatgcag gtcacagcgt ctaacaaata tgaaaatgtg tatattcacc 720ccggtctcca gccggcgcgc caggctccc 7492883DNAArtificial Sequencesequence of STAR2 2gggtgcttcc tgaattcttc cctgagaagg atggtggccg gtaaggtccg tgtaggtggg 60gtgcggctcc ccaggccccg gcccgtggtg gtggccgctg cccagcggcc cggcaccccc 120atagtccatg gcgcccgagg cagcgtgggg gaggtgagtt agaccaaaga gggctggccc 180ggagttgctc atgggctcca catagctgcc ccccacgaag acggggcttc cctgtatgtg 240tggggtccca tagctgccgt tgccctgcag gccatgagcg tgcgggtcat agtcgggggt 300gccccctgcg cccgcccctg ccgccgtgta gcgcttctgt gggggtggcg ggggtgcgca 360gctgggcagg gacgcagggt aggaggcggg gggcagcccg taggtaccct gggggggctt 420ggagaagggc gggggcgact ggggctcata cgggacgctg ttgaccagcg aatgcataga 480gttcagatag ccaccggctc cggggggcac ggggctgcga cttggagact ggccccccga 540tgacgttagc atgcccttgc ccttctgatc ctttttgtac ttcatgcggc gattctggaa 600ccagatcttg atctggcgct cagtgaggtt cagcagattg gccatctcca cccggcgcgg 660ccggcacagg tagcggttga agtggaactc tttctccagc tccaccagct gcgcgctcgt 720gtaggccgtg cgcgcgcgct tggacgaagc ctgccccggc gggctcttgt cgccagcgca 780gctttcgcct gcgaggacag agagaggaag agcggcgtca ggggctgccg cggccccgcc 840cagcccctga cccagcccgg cccctccttc caccaggccc caa 88332126DNAArtificial Sequencesequence of STAR3 3atctcgagta ctgaaatagg agtaaatctg aagagcaaat aagatgagcc agaaaaccat 60gaaaagaaca gggactacca gttgattcca caaggacatt cccaaggtga gaaggccata 120tacctccact acctgaacca attctctgta tgcagattta gcaaggttat aaggtagcaa 180aagattagac ccaagaaaat agagaacttc caatccagta aaaatcatag caaatttatt 240gatgataaca attgtctcca aaggaacaag gcagagtcgt gctagcagag gaagcacgtg 300agctgaaaac agccaaatct gctttgtttt catgacacag gagcataaag tacacaccac 360caactgacct attaaggctg tggtaaaccg attcatagag agaggttcta aatacattgg 420tccctcacag gcaaactgca gttcgctccg aacgtagtcc ctggaaattt gatgtccagt 480atagaaaagc agagcagtca aaaaatatag ataaagctga accagatgtt gcctgggcaa 540tgttagcagc accacactta agatataacc tcaggctgtg gactccctcc ctggggagcg 600gtgctgccgg cggcgggcgg gctccgcaac tccccggctc tctcgcccgc cctcccgttc 660tcctcgggcg gcggcggggg ccgggactgc gccgctcaca gcggcggctc ttctgcgccc 720ggcctcggag gcagtggcgg tggcggccat ggcctcctgc gttcgccgat gtcagcattt 780cgaactgagg gtcatctcct tgggactggt tagacagtgg gtgcagccca cggagggcga 840gttgaagcag ggtggggtgt cacctccccc aggaagtcca gtgggtcagg gaactccctc 900ccctagccaa gggaggccgt gagggactgt gcccggtgag agactgtgcc ctgaggaaag 960gtgcactctg gcccagatac tacacttttc ccacggtctt caaaacccgc agaccaggag 1020attccctcgg gttcctacac caccaggacc ctgggtttca accacaaaac cgggccattt 1080gggcagacac ccagctagct gcaagagttg tttttttttt tatactcctg tggcacctgg 1140aacgccagcg agagagcacc tttcactccc ctggaaaggg ggctgaaggc agggaccttt 1200agctgcgggc tagggggttt ggggttgagt gggggagggg agagggaaaa ggcctcgtca 1260ttggcgtcgt ctgcagccaa taaggctacg ctcctctgct gcgagtagac ccaatccttt 1320cctagaggtg gagggggcgg gtaggtggaa gtagaggtgg cgcggtatct aggagagaga 1380aaaagggctg gaccaatagg tgcccggaag aggcggaccc agcggtctgt tgattggtat 1440tggcagtgga ccctcccccg gggtggtgcc ggaggggggg atgatgggtc gaggggtgtg 1500tttatgtgga agcgagatga ccggcaggaa cctgccccaa tgggctgcag agtggttagt 1560gagtgggtga cagacagacc cgtaggccaa cgggtggcct taagtgtctt tggtctcctc 1620caatggagca gcggcggggc gggaccgcga ctcgggttta atgagactcc attgggctgt 1680aatcagtgtc atgtcggatt catgtcaacg acaacaacag ggggacacaa aatggcggcg 1740gcttagtcct acccctggcg gcggcggcag cggtggcgga ggcgacggca ctcctccagg 1800cggcagccgc agtttctcag gcagcggcag cgcccccggc aggcgcggtg gcggtggcgc 1860gcagccaggt ctgtcaccca ccccgcgcgt tcccaggggg aggagactgg gcgggagggg 1920ggaacagacg gggggggatt caggggcttg cgacgcccct cccacaggcc tctgcgcgag 1980ggtcaccgcg gggccgctcg gggtcaggct gcccctgagc gtgacggtag ggggcggggg 2040aaaggggagg agggacaggc cccgcccctc ggcagggcct ctagggcaag ggggcggggc 2100tcgaggagcg gaggggggcg gggcgg 212641625DNAArtificial Sequencesequence of STAR4 4gatctgagtc atgttttaag gggaggattc ttttggctgc tgagttgaga ttaggttgag 60ggtagtgaag gtaaaggcag tgagaccacg taggggtcat tgcagtaatc caggctggag 120atgatggtgg ttcagttgga atagcagtgc atgtgctgta acaacctcag ctgggaagca 180gtatatgtgg cgttatgacc tcagctggaa cagcaatgca tgtggtggtg taatgacccc 240agctgggtag ggtgcatgtg gtgtaacgac ctcagctggg tagcagtgtg tgtgatgtaa 300caacctcagc tgggtagcag tgtacttgat aaaatgttgg catactctag atttgttatg 360agggtagtgc cattaaattt ctccacaaat tggttgtcac gtatgagtga aaagaggaag 420tgatggaaga cttcagtgct tttggcctga ataaatagaa gacgtcattt ccagttaatg 480gagacaggga agactaaagg tagggtggga ttcagtagag caggtgttca gttttgaata 540tgatgaactc tgagagagga aaaacttttt ctacctctta gtttttgtga ctggacttaa 600gaattaaagt gacataagac agagtaacaa gacaaaaata tgcgaggtta tttaatattt 660ttacttgcag aggggaatct tcaaaagaaa aatgaagacc caaagaagcc attagggtca 720aaagctcata tgccttttta agtagaaaat gataaatttt aacaatgtga gaagacaaag 780gtgtttgagc tgagggcaat aaattgtggg acagtgatta agaaatatat gggggaaatg 840aaatgataag ttattttagt agatttattc ttcatatcta ttttggcttc aacttccagt 900ctctagtgat aagaatgttc ttctcttcct ggtacagaga gagcaccttt ctcatgggaa 960attttatgac cttgctgtaa gtagaaaggg gaagatcgat ctcctgtttc ccagcatcag 1020gatgcaaaca tttccctcca ttccagttct caaccccatg gctgggcctc atggcattcc 1080agcatcgcta tgagtgcacc tttcctgcag gctgcctcgg gtagctggtg cactgctagg 1140tcagtctatg tgaccaggag ctgggcctct gggcaatgcc agttggcagc ccccatccct 1200ccactgctgg gggcctccta tccagaaggg cttggtgtgc agaacgatgg tgcaccatca 1260tcattcccca cttgccatct ttcaggggac agccagctgc tttgggcgcg gcaaaaaaca 1320cccaactcac tcctcttcag gggcctctgg tctgatgcca ccacaggaca tccttgagtg 1380ctgggcagtc tgaggacagg gaaggagtga tgaccacaaa acaggaatgg cagcagcagt 1440gacaggagga agtcaaaggc ttgtgtgtcc tggccctgct gagggctggc gagggccctg 1500ggatggcgct cagtgcctgg tcggctgcaa gaggccagcc ctctgcccat gaggggagct 1560ggcagtgacc aagctgcact gccctggtgg tgcatttcct gccccactct ttccttctaa 1620gatcc 162551571DNAArtificial Sequencesequence of STAR5 5agcagagatc ttatttcccg tattcccttg tggcacagca cctcccacgc caaagcaaac 60caaagcaaag gagcccttga tgaggagggg ccttccccca acctggtctc ccacaggtcc 120tacatacgta cccaccccag acacacagag ctgcttcctg ctctcacacc agactgagct 180gtgcccagac atttccccta gcactaacca actctttcaa aaatacattt ttctctaaaa 240agaacaagtt taaacaaagt tgactcattt taagaactgt ttagaagata accttgtgtt 300tattaattat gtatttgcag aaattggagg cagaaggtta ccaacattgc ctggtgtcca 360gccaggaggt agagcgtggt ggcatccaga accttcctcc aactcctgcc tggcgtggtt 420tttattcatc tttgtattcc caagaaactt ctcagtgtct caggagtgtt aggcactcag 480tacgtgtttg gtagttacat gaatgaatgc ataatgacta agtgagttaa tggatgaagc 540taattgtctc tcccttttgc ttttccagag ctttccaagg tgaaagtgtt ggacactctt 600tcttcatctc agatttaatc aactaagaat gctgcaaatt gaacaccagt ccacaaaact 660caggaataca tgaaaagcat tgtgccttat ttttaactaa ctcaaattct atgtcagtct 720cccttttatg ctggatgttg gcgctaaatc tcagtgggtt cctcattctg ccagacctgt 780gtccagtttg ggggcttcac atagagccac cccatcacag gagagggaag ggtcttgctc 840ttggttgcca tcactccacc ctcttgtctt ccgagctttg atgttcactt tccttttcac 900cactcggaag cttcctgcca tgatacattg agacctcaat gttaatgcca attggggttt 960ggggttctca taaactcaga agtccaggaa aatcgcctgc tgcctcccac aacactctga 1020gggcattctg gaatcctacc acttacctgg agcctgctgg cctcaactgt tttgaagtct 1080gtgtctgggc catgcaggta aatgggagga tgttctgtgg ccataaaaat acccgaagtc 1140ccacctaaag ttgatgcagg gtcttctgca tttcattgca aaattgttct atcatttcta 1200tagttttcag cctacagtca ggggccagga ctttgcaccc ttggtaaacc tcaatctctt 1260ctccttcctg gcttctactc ctttctccct caatcccaaa tcaaggccct tgattgtctg 1320gaggtaggaa agcctggttc tggctcatga tatagtctac atcatagcct ttgtcatctc 1380atggattcac tcaacaaccg tgtgtggatg gggccaccca atatgtgcca ggagttgagg 1440acacgcaggg ttatgatgat gaaatagata aggggcccac actcacggac cctgcaggac 1500agtggagctg tggacccagc atgcgagtaa agacccagtg agctcaccag acagatcatt 1560taaatcaggt g 157161173DNAArtificial Sequencesequence of STAR6 6tgacccacca cagacatccc ctctggcctc ctgagtggtt tcttcagcac agcttccaga 60gccaaattaa acgttcactc tatgtctata gacaaaaagg gttttgacta aactctgtgt 120tttagagagg gagttaaatg ctgttaactt tttaggggtg ggcgagaggg atgacaaata 180acaacttgtc tgaatgtttt acatttctcc ccactgcctc aagaaggttc acaacgaggt 240catccatgat aaggagtaag acctcccagc cggactgtcc ctcggccccc agaggacact 300ccacagagat atgctaactg gacttggaga ctggctcaca ctccagagaa aagcatggag 360cacgagcgca cagagcaggg ccaaggtccc agggacagaa tgtctaggag ggagattggg 420gtgagggtaa tctgatgcaa ttactgtggc agctcaacat tcaagggagg gggaagaaag 480aaacagtccc tgtcaagtaa gttgtgcagc agagatggta agctccaaaa tttgaaactt 540tggctgctgg aaagttttag ggggcagaga taagaagaca taagagactt tgagggttta 600ctacacacta gacgctctat gcatttattt atttattatc tcttatttat tactttgtat 660aactcttata ataatcttat gaaaacggaa accctcatat acccatttta cagatgagaa 720aagtgacaat tttgagagca tagctaagaa tagctagtaa gtaaaggagc tgggacctaa 780accaaaccct atctcaccag agtacacact cttttttttt ttccagtgta atttttttta 840atttttattt tactttaagt tctgggatac atgtgcagaa ggtatggttt gttacatagg 900tatatgtgtg ccatagtgga ttgctgcacc tatcaacccg tcatctaggt ttaagcccca 960catgcattag ctatttgtcc tgatgctctc cctcccctcc ccacaccaga caggccttgg 1020tgtgtgatgt tcccctccct gtgtccatgt gttctcactg ttcagctccc acttatgagt 1080gagaacgtgt ggtatttggt tttctgttcc tgtgttagtt tgctgaggat gatggcttcc 1140agcttcatcc atgtccctgc aaaggacacg atc 117372101DNAArtificial Sequencesequence of STAR7 7atcatgccag cttaggcgac agagtgagac tggacataat aacaataata ataaaaataa 60ataaataaaa caattatctg agaggaaaaa tttgattcat aataaagaga ataaaggttt 120ttggcgtgtt tgttttgttt tcacctaaga acagctgttc ccctcattgg gttagtttta 180tttgcaagca gaaatcatct ccgcatgatt tccagggtga tggaaaactg aatatgaatc 240caccttctgc catctattca cttgtcacat ttaataagac actcatgcct attttagcat 300gttttcttcc ctaccaaatg agttagtaac atcaagagat taaaataaca caaataagaa 360cattgaaggt attcaaatgt tacatacaaa tattaaacac aatattatta taattattcc 420tggaaatgac attgcctcta ctctcaaggt aaaggtcatt tttcttgatt taaacttttt 480tctcaagttt gaaatctcta agtttcaacc cgtaatctat ttgcaagttt gtgcaaattt 540tagggattga atccatagta attagtgatt tattgtggtg tagggagaca agtcaaaaga 600atcaggactg ctaggtagat gactaaggaa aggatggttc acgaggtgac ataaagcact 660cagaagaaaa aggtcaggaa acggaggaca gaaaaaaacc taagttctgc tgggtgatgc 720tgaatttgtc atcacaaaat ctgcattgtg gaagctttag ctattgagga gattgctcaa 780gtgtagaact gagaacaata ggcagtgaac ccgagagaac atcaagagac tgagagaaaa 840tgaaccagac ttccaggtgc tccatgttcc aaccaacatt ttgtattgtc agaaggaatt 900gagaggcaaa aggaaaccca ataaaaaata aaacaggaaa gggcatacat gattaccacc 960ccttttctca ccagctgctc atggaccagc tttctcctag tgctattttc ttggtcactg 1020catcactctg ctaacatagt ttccccacta gctctgaggc tgtcccagag gggaagccag 1080ctgtcatctc cttcttccac actctgttgg aggaacctgt cattagcagc tccctactaa 1140acgcatttat gacaaacagg caggagataa ttaactagaa agtgaacaaa ctcaaacttc 1200agagcctctc atttgtatga atgcccttgt aaggtcttgg gcctatttta atatttataa 1260atgtgttatt ttcttctaaa gaaaaccacc aaattgtata agctacagaa tctgcaaaac 1320tgaggtccat ccatgcactc aggatacatt catagcatct ctgagctgga aaatatctta 1380aaggtcatat atgtcctcca acactgcaag aatctctctg gcagcattct tttaaaatca 1440tcatctaaaa gagggaaatc cccagctgtg tttggatttt gctctgtcac ttgtccagtt 1500tccccatcca taaaagggca acaatatgaa tttcctgata aggtagttgt taatataaat 1560acaaagtgcg tagccacttc cctaagaaaa atatggggtt tctgcttcac agtctaggga 1620gaggaaaaaa aaggggggtc agaagtgatt attattatca ttctatattg gaatgttttc 1680agacataaaa agctcaccac gtcttaggcc agacagatgc attatgaaag ttaagctaag 1740tcttcctcat catgagctgc acctatatcc ccattacttc ttctagaact gcataattta 1800tttattcttt cttcaaaagt ttgagagagc cattcttgtc ctctaagatt tttttttttt 1860tttttggaga cagagtctcc gtctgttgcc caggctggag tgcaatggca ctatctcagc 1920tcactgcaac ctctgcctcc cagattcaag tgattctcct gcctcagcct cccgagtagc 1980tgggattaca agcacgcacc accacaacca gctaattttt cgtatttttt agtagagacg 2040aggttttacc atgttggcca ggctggtctt gaactcctga cctcgggtga tccacccacc 2100t 210181821DNAArtificial Sequencesequence of STAR8 8gagatcacct cgaagagagt ctaacgtccg taggaacgct ctcgggttca caaggattga 60ccgaacccca ggatacgtcg ctctccatct gaggcttgct ccaaatggcc ctccactatt 120ccaggcacgt gggtgtctcc cctaactctc cctgctctcc tgagcccatg ctgcctatca 180cccatcggtg caggtccttt ctgaagagct cgggtggatt ctctccatcc cacttccttt 240cccaagaaag aagccaccgt tccaagacac ccaatgggac attccccttc cacctccttc 300tccaaagttg cccaggtgtt catcacaggt tagggagaga agcccccagg tttcagttac 360aaggcatagg acgctggcat gaacacacac acacacacac acacacacac acacacacac 420acacgactcg aagaggtagc cacaagggtc attaaacact tgacgactgt tttccaaaaa 480cgtggatgca gttcatccac gccaaagcca agggtgcaaa gcaaacacgg aatggtggag 540agattccaga ggctcaccaa accctctcag gaatattttc ctgaccctgg gggcagaggt 600tggaaacatt gaggacattt cttgggacac acggagaagc tgaccgacca ggcattttcc 660tttccactgc aaatgaccta tggcgggggc atttcacttt cccctgcaaa tcacctatgg 720cgaggtacct ccccaagccc ccacccccac ttccgcgaat cggcatggct cggcctctat 780ccgggtgtca ctccaggtag gcttctcaac gctctcggct caaagaagga caatcacagg 840tccaagccca aagcccacac ctcttccttt tgttataccc acagaagtta gagaaaacgc 900cacactttga gacaaattaa gagtccttta tttaagccgg cggccaaaga gatggctaac 960gctcaaaatt ctctgggccc cgaggaaggg gcttgactaa cttctatacc ttggtttagg 1020aaggggaggg gaactcaaat gcggtaattc tacagaagta aaaacatgca ggaatcaaaa 1080gaagcaaatg gttatagaga gataaacagt tttaaaaggc aaatggttac aaaaggcaac 1140ggtaccaggt gcggggctct aaatccttca tgacacttag atataggtgc tatgctggac 1200acgaactcaa ggctttatgt tgttatctct tcgagaaaaa tcctgggaac ttcatgcact 1260gtttgtgcca gtatcttatc agttgattgg gctcccttga aatgctgagt atctgcttac 1320acaggtcaac tccttgcgga agggggttgg gtaaggagcc cttcgtgtct cgtaaattaa 1380ggggtcgatt ggagtttgtc cagcattccc agctacagag agccttattt acatgagaag 1440caaggctagg tgattaaaga gaccaacagg gaagattcaa agtagcgact tagagtaaaa 1500acaaggttag gcatttcact ttcccagaga acgcgcaaac attcaatggg agagaggtcc 1560cgagtcgtca aagtcccaga tgtggcgagc ccccgggagg aaaaaccgtg tcttccttag 1620gatgcccgga acaagagcta ggcttccgga gctaggcagc catctatgtc cgtgagccgg 1680cgggagggag accgccggga ggcgaagtgg ggcggggcca tccttctttc tgctctgctg 1740ctgccgggga gctcctggct ggcgtccaag cggcaggagg ccgccgtcct gcagggcgcc 1800gtagagtttg cggtgcagag t 182191929DNAArtificial Sequencesequence of STAR9 9atgagccccc aaaaatgatc ctctggctta tgacaacctg atgcagccca ggaaatgcct 60gcaacatgcc cactagcagc tgggaacccc tctgtgagga agagaacgtt ttacattaag 120aaaccctttg ttttgcagca gagactattc aggtcacaca tgtgtggcct ctcagttctt 180tgagccattt gaagttctct atccttgctg ggaggctgag ctctccatgg aaacctggtc 240cgatagtgag aggagcagac cctctggaaa caccttttta cacctgacca aagcagccag 300tcatgggcca gtgatgcaac aaggtcaacc ggtgcattct ggcccctcag aaaagcagcc 360cccgggaagg tcaggaggag gctgctgact ccctcttccc ctgcagccgc cccaagcaca 420cccaggagcc ctgcaggttt gggttcacca ggtgccagca ggtcccacga tgctgcattt 480cttacgagct cctggaggat gcagatggtc ctggtcagag gctgcattct gagtatcagg 540agccatgggg caacgtttct gcgattgagg aaggggcatt tctggggtgg gcagaacaaa 600ggtctttggc tgagctggag catccgcctc catcagtgtt ttccggcaac tgtactatcc 660atcgtcttcc cttcccacag ctgaccatgg ctttggaaaa tgctctgaaa ctttcttttc 720agaagagttg actcccaact ccacacttag gggaagtcaa gcctacttct cagaattcag 780agaaggcata aaaaagaatt catttctaaa ggccctttag aagtaacttc aggtctgaca 840gcggccagct aatttctggt cgccttccag gaatcttctg actgcaaaaa aaaagcattt 900accacctgaa cacaaaccca gttacagata gaaaaacata gtcatttaaa tagaatataa 960gcatctggcc tctgcccatc ataatggagt aacacaaaaa tctattttca aaaggaaact 1020aaatattatt gaccaaaaca tgaatgggga gacctcaggg tgatacagct cttgcctgga 1080tggaatttgt aatcaagagg atgagacagg attgtaactt gtgccaatgt gaaagggttt 1140gctcaggtat cattcatttt gcttaaatgc atgggtaatt tccaaagttc tttggagctg 1200aatttcacaa tttagtgcag gtcctggtga gcccaccttg acttatctca cagtacaatg 1260cagtggcgtg gctacaatgc tgggcaagag aagccaatgt caacagccca ggagtggctg 1320ggtccttacc aggctcccag gcatgcttca tggtgggccc tgggctggga ggaacagcac 1380ctttgcctgg tccatgagta tctgggtcaa actctcctgt ggacacagaa ggccatggcg 1440acaggcattc ccaggaaaag aaaagggcag cagctgaaat cgtcaggtgg agaaggcagt 1500catccttgct cagtcaactc taatccggct gcctcctcct cagcttcagg gtgaacctct 1560cctaagctgt gtctttggta tctgatgggc attaggtgct ggtgaaaaag ctggagggtc 1620ctttgggata ttacagaagc ccaatctagc cttgtattca atatctaggc actctcaccc 1680ctgaagttct acgtttccag atttctgaaa acatgggaaa gcatgtgtgt gatgtctgag 1740gtccccctca gcctctggtg tagggttagg agggctctaa agggtggcag ctccagtgtc 1800ccagtggggc ctgaagttgg tcccttccct tcccagctcc catccatggt ttagcccaat 1860cccttccgta cctaagagta ctgcacatgg atgctccacg cagagcctct gctccactcc 1920caggaagtg 1929101167DNAArtificial Sequencesequence of STAR10 10aggtcaggag ttcaagacca gcctggccaa catggtgaaa ccctgtccct acaaaaaata 60caaaaattag ccgggcgtgg tggggggcgc ctataatccc agctactcag gatgctgaga 120caggagaatt gtttgaaccc gggaggtgga ggttgcagtg aactgagatc gcgccactgc 180actccagcct ggtgacagag agagactccg tctcaacaac agacaaacaa acaaacaaac 240aacaacaaaa atgtttactg acagctttat tgagataaaa ttcacatgcc ataaaggtca 300ccttctacag

tatacaattc agtggattta gtatgttcac aaagttgtac gttgttcacc 360atctactcca gaacatttac atcaccccta aaagaagctc tttagcagtc acttctcatt 420ctccccagcc cctgccaacc acgaatctac tntctgtctc tattctgaat atttcatata 480aaggagtcct atcatatggg ccttttacgt ctaccttctt tcacttagca tcatgttttt 540aagattcatc cacagtgtag cacgtgtcag ttaattcatt tcatcttatg gctggataat 600gctctattgt atgcatatcc ctcactttgc ttatccattc atcaactgat tgacatttgg 660gttatttcta ctttttgact attatgagta atgctgctat gaacattcct gtaccaatcg 720ttacgtggac atatgctttc aattctcctg agtatgtaac tagggttgga gttgctgggt 780catatgttaa ctcagtgttt catttttttg aagaactacc aaatggtttt ccaaagtgga 840tgcaacactt tacattccca ccagcaagat atgaaggttc caatgtctct acatttttgc 900caacacttgt gattttcttt tatttattta tttatttatt tatttttgag atggagtctc 960actctgtcac ccaggctgga gtgcagtggc acaatttcag ctcactgcaa tctccacctc 1020tcgggctcaa gcgatactcc tgcctcaacc tcccgagtaa ctgggattac aggcgcccac 1080caccacacca agctaatttt ttgtattttt agtagagacg gggtttcatc atgtcggcca 1140ggntgtactc gaactctgac ctcaagt 1167111377DNAArtificial Sequencesequence of STAR11 11gattctgggt gggtttgatg atctgagagt cccttgaata aaaagaattc tagaaaagct 60gtgaaacttc acctttcccc tattcttaac cttacttgcc tttgggaggc tgaggcagga 120ggatgactta aggccaggag tttgagaatg tagtgagcta tgaccacacc ggttacactc 180aagcctgggc gagaccacaa caaaaacctt acctgccaac tgctccatgc tggaaattta 240tttcgtttct tggattgtgg aaagaactgg cttactgaaa accacacttc tctaaaaccc 300ttcttccagt taggtgttaa gattttaaca gcctttccta tctgaataaa aactgcacac 360aaagtaaact taagagatgt caacaactca tctgtttgtt acaagatgag tctccatgct 420tcatcgcctg tggggaatcc tcatcagcgt ctagtggcaa agactcctgt gtgctcaccg 480aaacgctccc cttcctccag ggcacacagt cacatggatt tcccatgcac cctggcagct 540cagcaggagt ccatgactta agaaggccaa tggactgtgg gtgaagtctg tggacgggga 600agccacatgc gtcacttcca ggcctgggcg tgtgcatcct ccactctctt cccctgtggg 660tgcagaaggc ggggcagagg gccctgaaac cttggaggtc ggtggagccc aaaatgaagg 720agcgtgggcc tctgggtctt catgtaaatt taggtaacac tgaactgtca ggtgaacaag 780aaataaacgt caaatgtatt cagtcgatta gatttggtga tggttgttac agcggttacc 840ctccctcaac ataataaatt ttcaaacaac tcataatggc tcactcatgt ataaaatatt 900ccatatgaaa tcccgggata acatgcttat tctagctcaa gcttaatcag agtagtccat 960ctgagggagg agatagtaga gggcagcaag gggttgtcac tgaagataac tagccttgct 1020aaaagaatgg ttgaagaagt gagctacaga tagggtaaat ccacatctca gacattctgt 1080gatggtcctg atattatcct aaagtaaaat gtagagttga accattttaa ttagattcta 1140gaattctatt aatttataag atgggcattt ccacaaagga ctaaacaaag tacaagagga 1200ttaaataatc atccacatgg gaggcaccgc cttgcacttt aaaatgatgg agcttatcaa 1260gactggctgt ggatatctgt ccctgggagg gttttttccc ccattttttt cctttttgag 1320acatgttctc gctatgttgc ccaggctggt cttgaactcc tgggctcaag tgatcct 1377121051DNAArtificial Sequencesequence of STAR12 12atcctgcttc tgggaagaga gtggcctccc ttgtgcaggt gactttggca ggaccagcag 60aaacccaggt ttcctgtcag gaggaagtgc tcagcttatc tctgtgaagg gtcgtgataa 120ggcacgagga ggcaggggct tgccaggatg ttgcctttct gtgccatatg ggacatctca 180gcttacgttg ttaagaaata tttggcaaga agatgcacac agaatttctg taacgaatag 240gatggagttt taagggttac tacgaaaaaa agaaaactac tggagaagag ggaagccaaa 300caccaccaag tttgaaatcg attttattgg acgaatgtct cactttaaat ttaaatggag 360tccaacttcc ttttctcacc cagacgtcga gaaggtggca ttcaaaatgt ttacacttgt 420ttcatctgcc tttttgctaa gtcctggtcc cctacctcct ttccctcact tcacatttgt 480cgtttcatcg cacacatatg ctcatcttta tatttacata tatataattt ttatatatgg 540cttgtgaaat atgccagacg agggatgaaa tagtcctgaa aacagctgga aaattatgca 600acagtgggga gattgggcac atgtacattc tgtactgcaa agttgcacaa cagaccaagt 660ttgttataag tgaggctggg tggtttttat tttttctcta ggacaacagc ttgcctggtg 720gagtaggcct cctgcagaag gcattttctt aggagcctca acttccccaa gaagaggaga 780gggcgagact ggagttgtgc tggcagcaca gagacaaggg ggcacggcag gactgcagcc 840tgcagagggg ctggagaagc ggaggctggc acccagtggc cagcgaggcc caggtccaag 900tccagcgagg tcgaggtcta gagtacagca aggccaaggt ccaaggtcag tgagtctaag 960gtccatggtc agtgaggctg agacccaggg tccaatgagg ccaaggtcca gagtccagta 1020aggccgagat ccagggtcca gggaggtcaa g 1051131291DNAArtificial Sequencesequence of STAR13 13ctgccctgat cccttaatgc ttttggccca gagcaccccg ctaagtccaa ccccagaggg 60gcctcatccg caaagcctcg ggaagaggac agtgacggag gcggctgccc tgtgagctgc 120acggggcaga atgtcctttt ggcgtcatgt tggatgtcca cacatccata tggggtcagt 180tctattagga ttccttcggg aagaggtaga gggtaggagg ggttaagcca cgagacgagg 240catgcagagg ggtggcctgg atgggtctgc actgctgtcc atgcacacgg ggagcgttgc 300aaattgtgct tcccagccca tagtgccccc acagaggagc ccgggagtcc ctggtgggcg 360tctgtgttcc tgcaaggagc cagtggagat ggccccgtga actctcatcc cccttgcctt 420ggtggggtct ctggcaggtt tatggagccg tacatctttg ggagccgcct ggaccacgac 480atcatcgacc tggaacagac agccacgcac ctccagctgg ccttgaactt caccgcccac 540atggcctacc gcaagggcat catcttgttt ataagccgca accggcagtt ctcgtacctg 600attgagaaca tggcccgtga ctgtggcgag tacgcccaca ctcgctactt caggggcggc 660atgctgacca acgcgcgcct cctctttggc cccacggtcc gcctgccgga cctcatcatc 720ttcctgcaca cgctcaacaa catctttgag ccacacgtgg ccgtgagaga cgcagccaag 780atgaacatcc ccacagtggg catcgtggac accaactgca acccctgcct catcacctac 840cctgtacccg gcaatgacga ctctccgctg gctgtgcacc tctactgcag gctcttccag 900acggccatca cccgggccaa ggagaagcgg cagcaggttg aggctctcta tcgcctgcag 960ggccagaagg agcccgggga ccaggggcca gcccaccctc ctggggctga catgagccat 1020tccctgtgat gttcactctc ctcccaaagc aaaccacagc caagcctgtc tgagctggga 1080gtccccttcc ccagccctgg gtcagcggca tcctcagtcg ttgttactta ctcagctgat 1140gtcacagtgc agacatccac cgttccacca cagaaccagt ggctgagcgg accaacgttg 1200ccatgtgcgt ttgctctgtg gggaacagag cacagagggt gagcgacatg tgcagaacgg 1260ccccttggct gcagttagga cctcagtggc t 129114711DNAArtificial Sequencesequence of STAR14 14agcaaggacc agggctctgc ctccccagtc agcatgagca gagcagactc ctttgagcag 60agcatcaggg cagaaataga acagtttctg aatgagaaaa gacagcatga gacccaaaaa 120tgtgatgggt cagtggagaa gaaaccagac acacatgaaa attcggcgaa gtcactctcg 180aaatcccacc aagagccggc tacaaaggtg gtgcaccggc agggcctgat gggcgtccag 240aaggagttcg ccttctgcag acctcccccg gttagcaaag acaaacgtgc agcccagaag 300cctcaggtcc aaggtcacga ccacgaccac gcaggagaag gagggcagca caaagccagc 360aacccccacc gcccttcaga agcagtacag aataaaagtg ggattaaaag gaacgccagc 420accgcaagga ggggaaagcg agtcacgagc gccgtacagg cgcccgaggc gtccgactcc 480agcagcgacg acggcattga ggaggccatc cagctgtacc aggtgcagaa aacacacaag 540gaggccgacg gggacccgcc ccagagggtc cagctccaag aggaaagagc acctgcccct 600cccgcacaca gcacaagcag cgccacaaaa agtgccttgc cagagaccca caggaaaaca 660cccagcaaga agaagccagt gcccaccaag accacggacc ctggtccagg g 711151876DNAArtificial Sequencesequence of STAR15 15cagtacatgc agaactgagt ccaaacgaga cggacagcaa acccggcagt gggctcccag 60acattcctgg gggaaaggga tcctaaccac aggcagttaa agtcatctcc tccaaccctc 120tatgacacag gctgtgcgct gtcatttaaa agctgagtga aatttaaccc ttttcccatt 180tagaaaaaca aagcgcagct ggctgccagc actcatttaa ttttacataa acgtgctctt 240tgaggctgaa gcaaatctga ctgattttca atgtgaaaat aaaatgtaaa aactgttctt 300ggaattattt ctaaacagaa catcagaatc gtctgaatca tcagaatcgg ctattttgga 360aaaatcggat tcatcaaacg aatcttcggc caacaactgt tagagaacga tgttaacacc 420acgcatagga atgttacatt ttctagaatt tgacattttc attgacggaa aattactgta 480tcttgtatat ggaaatacca ctactaaaaa cataatgcta taaatagaat gatgtctttt 540gtttccaaag tcaatatact cgagcaatgc aaaaataata ataaaagtga gatacttcat 600ggcaaagctg ccgcaggata aacattgcag ccacaagtgc ccccagtatt ctcggggcaa 660actggaaaag ggctaacagg caacattttc atgttattct actgagtgca gtaattattt 720ttaaaaatat acatgaataa tgaaaaaact gtggtatggt tttaaagaaa tttccataac 780ctggtgaaac tcttcacaca gggtaatagg ttcataaagc cttggtcctc tgcaaaacaa 840gcatcaactt gacaatgact aaaagaagca acagcaaaac tgtcacgcat ttggagccat 900ggcctgggtt gggccggtgt aaagctctcc gccctctgga gcaagtctgg gccccagcgg 960ctggcatgtg ggcactgcag ggcctgggtt gggcaggtgt gcagctctcc gtcatctgag 1020cctagtctga ggcctggtgg ctggcacgtg ggccctgcag ggcctctact tctcacccca 1080gctccacttc cctccctgcc ctcactgggt ctcacagagc caatgaacac tggggtcaga 1140ttcagggccc agcatccact gcagtgggca ctgcccttcc acaaggcctg gctccaggaa 1200gcaaccccca cctcagccac acagtagggc aacaggaaat cccattcccc catgccagtg 1260actacaccag ggaaggggct cacgtgaggc tggccccagg cctgctgtga gaccgcgttg 1320tctatgagct tggatttaag gaacttggga gcaagaagct ttctttcatt acgggccacc 1380agcagggaaa aaagttagcc caacgcagtt gacagtcaca cccccaccag gaccccaggg 1440cacagaagga gggaagagga caacagagga tgaggtgggg ccagcagagg gacagagaag 1500agctgcctgc cctggaacag gcagaaagca tcccacgtgc aagaaaaagt aggccagcta 1560gacttaaaat cagaactacc gctcatcaaa agatagtgta acatttgggg tgctataatt 1620ttaacatgtc ccccaaaagg catgtgttgg aaatttaatc cccaacaaac cagggctggg 1680aggtggagcc tcatgagagg tggtgaggcc atgagggtgg agtgaatgga tgaatgccat 1740tgtctcggga atgggcctct tctacaagga cgagttcagc ccccctttct cttgctcacc 1800ctctctttgc cctttcgcta gggagtgacg taacaagaag gccctcacaa gatgctggca 1860ccttgatctt ggactc 1876161282DNAArtificial Sequencesequence of STAR16 16cgcccacctc ggctttccaa agtgctggga ttacaggcat gagtcactgc gcccatcctg 60attccaagtc tttagataat aacttaactt tttcgaccaa ttgccaatca ggcaatcttt 120gaatctgcct atgacctagg acatccctct ccctacaagt tgccccgcgt ttccagacca 180aaccaatgta catcttacat gtattgattg aagttttaca tctccctaaa acatataaaa 240ccaagctata gtctgaccac ctcaggcacg tgttctcagg acctccctgg ggctatggca 300tgggtcctgg tcctcagatt tggctcagaa taaatctctt caaatatttt ccagaatttt 360actcttttca tcaccattac ctatcaccca taagtcagag ttttccacaa ccccttcctc 420agattcagta atttgctaga atggccacca aactcaggaa agtattttac ttacaattac 480caatttatta tgaagaactc aaatcaggaa tagccaaatg gaagaggcat agggaaaggt 540atggaggaag gggcacaaag cttccatgcc ctgtgtgcac accaccctct cagcatcttc 600atgtgttcac caactcagaa gctcttcaaa ctttgtcatt taggggtttt tatggcagtt 660ccactatgta ggcatggttg ataaatcact ggtcatcggt gatagaactc tgtctccagc 720tcctctctct ctcctcccca gaagtcctga ggtggggctg aaagtttcac aaggttagtt 780gctctgacaa ccagccccta tcctgaagct attgaggggt cccccaaaag ttaccttagt 840atggttggaa gaggcttatt atgaataaca aaagatgctc ctatttttac cactagggag 900catatccaag tcttgcggga acaaagcatg ttactggtag caaattcata caggtagata 960gcaatctcaa ttcttgcctt ctcagaagaa agaatttgac caagggggca taaggcagag 1020tgagggacca agataagttt tagagcagga gtgaaagttt attaaaaagt tttaggcagg 1080aatgaaagaa agtaaagtac atttggaaga gggccaagtg ggcgacatga gagagtcaaa 1140caccatgccc tgtttgatgt ttggcttggg gtcttatatg atgacatgct tctgagggtt 1200gcatccttct cccctgattc ttcccttggg gtgggctgtc cgcatgcaca atggcctgcc 1260agcagtaggg aggggccgca tg 128217793DNAArtificial Sequencesequence of STAR17 17atccgagggg aggaggagaa gaggaaggcg agcagggcgc cggagcccga ggtgtctgcg 60agaactgttt taaatggttg gcttgaaaat gtcactagtg ctaagtggct tttcggattg 120tcttatttat tactttgtca ggtttcctta aggagagggt gtgttggggg tgggggagga 180ggtggactgg ggaaacctct gcgtttctcc tcctcggctg cacagggtga gtaggaaacg 240cctcgctgcc acttaacaat ccctctatta gtaaatctac gcggagactc tatgggaagc 300cgagaaccag tgtcttcttc cagggcagaa gtcacctgtt gggaacggcc cccgggtccc 360cctgctgggc tttccggctc ttctaggcgg cctgatttct cctcagccct ccacccagcg 420tccctcaggg acttttcaca cctccccacc cccatttcca ctacagtctc ccagggcaca 480gcacttcatt gacagccaca cgagccttct cgttctcttc tcctctgttc cttctctttc 540tcttctcctc tgttccttct ctttctctgt cataatttcc ttggtgcttt cgccacctta 600aacaaaaaag agaaaaaaat aaaataaaaa aaacccattc tgagccaaag tattttaaga 660tgaatccaag aaagcgaccc acatagccct ccccacccac ggagtgcgcc aagacgcacc 720caggctccat cacagggccg agagcagcgc cactctggtc gtacttttgg gtcaagagat 780cttgcaaaag agg 79318492DNAArtificial Sequencesequence of STAR18 18atctttttgc tctctaaatg tattgatggg ttgtgttttt tttcccacct gctaataaat 60attacattgc aacattcttc cctcaacttc aaaactgctg aactgaaaca atatgcataa 120aagaaaatcc tttgcagaag aaaaaaagct attttctccc actgattttg aatggcactt 180gcggatgcag ttcgcaaatc ctattgccta ttccctcatg aacattgtga aatgaaacct 240ttggacagtc tgccgcattg cgcatgagac tgcctgcgca aggcaagggt atggttccca 300aagcacccag tggtaaatcc taacttatta ttcccttaaa attccaatgt aacaacgtgg 360gccataaaag agtttctgaa caaaacatgt catctttgtg gaaaggtgtt tttcgtaatt 420aatgatggaa tcatgctcat ttcaaaatgg aggtccacga tttgtggcca gctgatgcct 480gcaaattatc ct 492191840DNAArtificial Sequencesequence of STAR19 19tcacttcctg atattttaca ttcaaggcta gctttatgca tatgcaacct gtgcagttgc 60acagggcttt gtgttcagaa agactagctc ttggtttaat actctgttgt tgccatcttg 120agattcatta taatataatt tttgaatttg tgttttgaac gtgatgtcca atgggacaat 180ggaacattca cataacagag gagacaggtc aggtggcagc ctcaattcct tgccaccctt 240ttcacataca gcattggcaa tgccccatga gcacaaaatt tgggggaacc atgatgctaa 300gactcaaagc acatataaac atgttacctc tgtgactaaa agaagtggag gtgctgacag 360cccccagagg ccacagttta tgttcaaacc aaaacttgct tagggtgcag aaagaaggca 420atggcagggt ctaagaaaca gcccatcata tccttgttta ttcatgttac gtccctgcat 480gaactaatca cttacactga aaatattgac agaggaggaa atggaaagat agggcaaccc 540atagttcttt ttccttttag tctttcctta tcagtaaacc aaagatagta ttggtaaaat 600gtgtgtgagt taattaatga gttagtttta ggcagtgttt ccactgttgg ggtaagaaca 660aaatatatag gcttgtattg agctattaaa tgtaaattgt ggaatgtcag tgattccaag 720tatgaattaa atatccttgt atttgcattt aaaattggca ctgaacaaca aagattaaca 780gtaaaattaa taatgtaaaa gtttaatttt tacttagaat gacattaaat agcaaataaa 840agcaccatga taaatcaaga gagagactgt ggaaagaagg aaaacgtttt tattttagta 900tatttaatgg gactttcttc ctgatgtttt gttttgtttt gagagagagg gatgtggggg 960cagggaggtc tcattttgtt gcccaggctg gacttgaact cctgggctcc agctatcctg 1020ccttagcttc ttgagtagct gggactacag gcacacacca cagtgtctga cattttctgg 1080attttttttt tttttttatt ttttttgtga gacaggttct ggctctgtta ctcaggttgc 1140agtgcagtgg catgatagcg gctcactgca gcctcaacct cctcagctta agctactctc 1200ccacttcagc ctcctgagta gccaggacta cagttgtgtg ccaccacacc tgtggctaat 1260ttttgtagag atggggtctc tccacgttgc cgaggctggt ctccaactcc tggtctcaag 1320cgaacctcct gacttggcct cccgaagtgc tgggattaca ggcttgagcc actgcatcca 1380gcctgtcctc tgtgttaaac ctactccaat ttgtctttca tctctacata aacggctctt 1440ttcaaagttc ccatagacct cactgttgct aatctaataa taaattatct gccttttctt 1500acatggttca tcagtagcag cattagattg ggctgctcaa ttcttcttgg tatattttct 1560tcatttggct tctggggcat cacactctct ttgagttact cattcctcat tgatagcttc 1620ttcctagtct tctttactgg ttcttcctct tctccctgac tccttaatat tgtttttctc 1680cccaggcttt agttcttagt cctcttctgt tatctattta cacccaattc tttcagagtc 1740tcatccagag tcatgaactt aaacctgttt ctgtgcagat aattcacatt attatatctc 1800cagcccagac tctcccgcaa actgcagact gatcctactg 184020780DNAArtificial Sequencesequence of STAR20 20gatctcaagt ttcaatatca tgttttggca aaacattcga tgctcccaca tccttaccta 60aagctaccag aaaggctttg ggaactgtca acagagctac agaaaagtca gtaaagacca 120atggacccct caaacaaaaa cagccaagct tttctgccaa aaagatgact gagaagactg 180ttaaagcaaa aaactctgtt cctgcctcag atgatggcta tccagaaata gaaaaattat 240ttcccttcaa tcctctaggc ttcgagagtt ttgacctgcc tgaagagcac cagattgcac 300atctcccctt gagtgaagtg cctctcatga tacttgatga ggagagagag cttgaaaagc 360tgtttcagct gggcccccct tcacctttga agatgccctc tccaccatgg aaatccaatc 420tgttgcagtc tcctttaagc attctgttga ccctggatgt tgaattgcca cctgtttgct 480ctgacataga tatttaaatt tcttagtgct ttagagtttg tgtatatttc tattaataaa 540gcattatttg tttaacagaa aaaaagatat atacttaaat cctaaaataa aataaccatt 600aaaaggaaaa acaggagtta taactaataa gggaacaaag gacataaaat gggataataa 660tgcttaatcc aaaataaagc agaaaatgaa gaaaaatgaa atgaagaaca gataaataga 720aaacaaatag caatatgaaa gacaaacttg accgggtgtg gtggctgatg cctgtaatcc 78021607DNAArtificial Sequencesequence of STAR21 21gatcaataat ttgtaatagt cagtgaatac aaaggggtat atactaaatg ctacagaaat 60tccattcctg ggtataaatc ctagacatat ttatgcatat gtacaccaag atatatctgc 120aagaatgttc acagcaaatc tctttgtagt agcaaaaggc caaaaggtct atcaacaaga 180aaattaatac attgtggcac ataatggcat ccttatgcca ataaaaatgg atgaaattat 240agttaggttc aaaaggcaag cctccagata atttatatca tataattcca tgtacaacat 300tcaacaacaa gcaaaactaa acatatacaa atgtcaggga aaatgatgaa caaggttaga 360aaatgattaa tataaaaata ctgcacagtg ataacattta atgagaaaaa aagaaggaag 420ggcttaggga gggacctaca gggaactcca aagttcatgg taagtactaa atacataatc 480aaagcactca aaatagaaaa tattttagta atgttttagc tagttaatat cttacttaaa 540acaaggtcta ggccaggcac ggtggctcac acctgtaatc ccagcacttt gggaggctga 600ggcgggt 607221380DNAArtificial Sequencesequence of STAR22 22cccttgtgat ccacccgcct tggcctccca aagtgctggg attacaggcg tgagtcacta 60cgcccggcca ccctccctgt atattatttc taagtatact attatgttaa aaaaagttta 120aaaatattga tttaatgaat tcccagaaac taggatttta catgtcacgt tttcttatta 180taaaaataaa aatcaacaat aaatatatgg taaaagtaaa aagaaaaaca aaaacaaaaa 240gtgaaaaaaa taaacaacac tcctgtcaaa aaacaacagt tgtgataaaa cttaagtgcc 300tgaaaattta gaaacatcct tctaaagaag ttctgaataa aataaggaat aaaataatca 360catagttttg gtcattggtt ctgtttatgt gatggattat gtttattgat ttgtgtatgt 420tgaacttatc tcaatagatg cagacaaggc cttgataaaa gtttttaaca ccttttcatg 480ttgaaaactc tcaatagact aggtattgat gaaacatatc tcaaaataat agaagctatt 540tatgataaac ccatagccaa tatcatactg agtgggcaaa agctggaagc attccctttg 600aaaactggca caagacaagg atgccctctc tcaccactcc tattaaatgt agtattggaa 660gttctggcca gagcaatcag gcaggagaaa gaaaaggtat taaaatagga agagaggaag 720tcaaattgtc tctgtttgca gtaaacatga ttgtatattt agaaaacccc attgtctcat 780cctaaaaact ccttaagctg ataaacaact tcagcaaagt ctcaggatac aaaatcaatg 840tgcaaaaatc acaagcattc ctatacaccg ataatagaca gcagagagcc aaatcatgag 900tgaagtccca ttcacaattg cttcaaagaa aataaaatac ttaggaatac aactttcacg 960ggacatgaag gacattttca aggacaacta aaaaccactg ctcaaggaaa tgagagagga 1020cacaaagaaa tggaaaaaca ttccatgctc atggaagaat caatatcatg aaaatggcca 1080tactgcccaa agtaatttat agattcaatg ctaaccccat caagccacca ttgactttct 1140tcacagaact agaaaaaaac tattttaaaa ctcatatgta gtcaaaaaga gtcggtatag

1200ccaagacaat cctaagcata aagaacaaag ctggatgcat cacgctgact tcaaaccata 1260ctacaaggct acagtaacca aaacagcatg gtactggtac caaaacagat agatagaccg 1320atagaacaga acagaggcct cggaaataac accacacatc tacaaccctt tgatcttcaa 1380231246DNAArtificial Sequencesequence of STAR23 23atcccctcat ccttcagggc agctgagcag ggcctcgagc agctggggga gcctcactta 60atgctcctgg gagggcagcc agggagcatg gggtctgcag gcatggtcca gggtcctgca 120ggcggcacgc accatgtgca gccgccccca cctgttgctc tgcctccgcc acctggccat 180gggcttcagc agccagccac aaagtctgca gctgctgtac atggacaaga agcccacaag 240cagctagagg accttgtgtt ccacgtgccc agggagcatg gcccacagcc caaagaccag 300tcaggagcag gcaggggctt ctggcaggcc cagctctacc tctgtcttca cacagatggg 360agatttctgt tgtgattttg agtgatgtgc ccctttggtg acatccaaga tagttgctga 420agcaccgctc taacaatgtg tgtgtattct gaaaacgaga acttctttat tctgaaataa 480ttgatgcaaa ataaattagt ttggatttga aattctattc atgtaggcat gcacacaaaa 540gtccaacatt gcatatgaca caaagaaaag aaaaagcttg cattccttaa atacaaatat 600ctgttaacta tatttgcaaa tatatttgaa tacacttcta ttatgttaca tataatatta 660tatgtatatg tatatataat atacatatat atgttacata taatatactt ctattatgtt 720acatataata tttatctata agtaaataca taaatataaa gatttgagta gctgtagaac 780attgtcttat gtgttatcag ctactactac aaaaatatct cttccactta tgccagtttg 840ccatataaat atgatcttct cattgatggc ccagggcaag agtgcagtgg gtacttattc 900tctgtgagga gggaggagaa aagggaacaa ggagaaagtc acaaagggaa aactctggtg 960ttgccaaaat gtcaagtttc acatattccg agacggaaaa tgacatgtcc cacagaagga 1020ccctgcccag ctaatgtgtc acagatatct caggaagctt aaatgatttt tttaaaagaa 1080aagagatggc attgtcactt gtttcttgta gctgaggctg tgggatgatg cagatttctg 1140gaaggcaaag agctcctgct ttttccacac cgagggactt tcaggaatga ggccagggtg 1200ctgagcacta caccaggaaa tccctggaga gtgtttttct tactta 124624939DNAArtificial Sequencesequence of STAR24 24acgaggtcac gagttcgaga ccagcctggc caagatggtg aagccctgtc tctactaaaa 60atacaacaag tagccgggcg cggtgacggg cgcctgtaat cccagctact caggaggctg 120aagcaggaga atctctagaa cccaggaggc ggaggtgcag tgagctgaga ctgccccgct 180gcactctagc ctgggcaaca cagcaagact ctgtctcaaa taaataaata aataaataaa 240taaataaata aataaataaa tagaaaggga gagttggaag tagatgaaag agaagaaaag 300aaatcctaga tttcctatct gaaggcacca tgaagatgaa ggccacctct tctgggccag 360gtcctcccgt tgcaggtgaa ccgagttctg gcctccattg gagaccaaag gagatgactt 420tggcctggct cctagtgagg aagccatgcc tagtcctgtt ctgtttgggc ttgatcctgt 480atcacttgat tgtctctcct ggactttcca tggattccag ggatgcaact gagaagttta 540tttttaatgc acttacttga agtaagagtt attttaaaac attttagcaa aggaaatgaa 600ttctgacagg ttttgcactg aagacattca catgtgagga aaacaggaaa accactatgc 660tagaaaaagc aaatgctgtt gagattgtct cacaaacaca aattgcgtgc cagcaggtag 720gtttgagcct caggttgggc acattttacc ttaagcgcac tgttggtgga acttaaggtg 780actgtaggac ttatatatac atacatacat ataatatata tacatattta tgtgtatata 840cacacacaca cacacacaca cacacagggt cttgctatct tgcccagggt ggtctccaac 900tctgggtctc aagcgatcct ctgcctcccc ttcccaaag 939251067DNAArtificial Sequencesequence of STAR25 25ataaaaaaat aaaaaaccct gctctaattt gcaaaggctc tatctttcct cccaaccacc 60tgaaatttta gtgaaaacgg ggcttcctgt aggaaggagt agctagctat cccggtccgc 120tacaggttat cagtgcgtga ataccctgac tcctaaggct caggatttga ctgggtcgcc 180tcgtccgact gccccgcccc caacgcggac ccacgtcacc gcgcgccagc ctgcggccgt 240cctgacctcg cgggatttga gcttcggtgc caacaaacac tcccaccgcg gctgcgtcca 300ctttacctgc cggcggcgac cagcttctga agaaaagtgt ccaccatggt gtcgaggagc 360ttcaccctcg aaatggtagt gccgggtggc acagattccg aagacgaccc ctcatgcctt 420ttttcctcac agccgctgcc tagattggcg ctacttgctt cggccatgtt gaagttgaac 480ctccaaatct aactggcccg gcctccccgc ctgccggagc tcccgattgg ccgctcccgc 540gaagggtgcc tccgattgga agcagtagaa cgtctgtcac cgagcagggc gggggcgggg 600aagtcatcgg aggctgaggg cagcggggag gcgaggctct gcgcggtggg atgtccgcga 660ccggaaaaat acgcgcaagc caaagctcgg gggctcaata aaaactttta attacatttc 720agagacttcg tacagtgcaa cagtgaatat tcactgttaa ttttcacaag agtccatttc 780atcaaacgtt cagagagtct gccttttcat tcccttgttc ctcagtgctc caatcaggtt 840tccagtctcc cagaggtttc ttttagtttt gattaccgac caaaactcca gtttagggag 900aatggaagtc caccgtccca tccccaccaa aacatatttc agtcaaaccc aatcccagtc 960cctaaagaat taggaaagta tgggccaagg gtccttttaa ttatacacac atcaccctta 1020aaactgcgtg tgtgtacgag aaataaagaa aaacacaaga ggggctg 106726540DNAArtificial Sequencesequence of STAR26 26ccccctgaca agccccagtg tgtgatgttc cccactctgt gtccatgcat tctcattgtt 60caactcccat ctgtgagtga gaacatgcag tgtttggttt tctgtccttg agatagtttg 120ctgagaatga tggtttccag cttcatccat gtccttgcaa aggaagtgaa cttatccttt 180tttatggctt catagtattc catggcacat atgtgccaca tttttttaat ccagtctatc 240attgatggac atttgggttg gttccaagtc tttgctattg tgaatagcac cacaattaac 300atatgtgtgc atgtatacat ctttatagta gcatgattta taatccttcg ggtatatacc 360ctgtaatggg atcgctgggt caaatggtat ttctagttct agatccttga ggaatcacca 420cactgctttc cacaatggtt gaactaattt acgctcccac cagcagtgta aaagcattcc 480tatttctcca cgtcctctcc agtatctgtt gtttcctgac tttttaatga tcatcattct 540271520DNAArtificial Sequencesequence of STAR27 27cttggccctc acaaagcctg tggccaggga acaattagcg agctgcttat tttgctttgt 60atccccaatg ctgggcataa tgcctgccat tatgagtaat gccggtagaa gtatgtgttc 120aaggaccaaa gttgataaat accaaagaat ccagagaagg gagagaacat tgagtagagg 180atagtgacag aagagatggg aacttctgac aagagttgtg aagatgtact aggcaggggg 240aacagcttaa ggagagtcac acaggaccga gctcttgtca agccggctgc catggaggct 300gggtggggcc atggtagctt tcccttcctt ctcaggttca gagtgtcagc cttgaacttc 360taattcccag aggcatttat tcaatgtttt cttctagggg catacctgcc ctgctgtgga 420agactttctt ccctgtgggt cgccccagtc cccagatgag acggtttggg tcagggccag 480gtgcaccgtt gggtgtgtgc ttatgtctga tgacagttag ttactcagtc attagtcatt 540gagggaggtg tggtaaagat ggagatgctg ggtcacatcc ctagagaggt gttccagtat 600gggcacatgg gagggctgga aggataggtt actgctagac gtagagaagc cacatccttt 660aacaccctgg cttttcccac tgccaagatc cagaaagtcc ttgtggtttc gctgctttct 720cctttttttt tttttttttt tttctgagat ggagtctggc tctgtcgccc aggctggagt 780gcagtggcac gatttcggct cactgcaagt tccgcctcct aggttcatac cattctccca 840cctcagcctc ccgagtagct gggactacag gcgccaccac acccagctaa ttttttgtat 900ttttagtaga gacggcgttt caccatgtta gccaggatgg tcttgatccg cctgcctcag 960cctcccaaag tgctgggatt acaggcgtga gccaccgcgc ccggcctgct ttcttctttc 1020atgaagcatt cagctggtga aaaagctcag ccaggctggt ctggaactct tgacctcaag 1080tgatctgcct gcctcagcct cccaaagtgc tgagattaca ggcatgagcc agtccgaatg 1140tggctttttt tgttttgttt tgaaacaagg tctcactgtt gcccaggctg cagtgcagtg 1200gcatacctca gctccactgc agcctcgacc tcctgggctc aagcaatcct cccaactgag 1260cctccccagt agctggggct acaagcgcat gccaccacgc ctggctattt tttttttttt 1320tttttttttt gagaaggagt ttcattcttg ttgcccaggc tggagtgcaa tggcacagtc 1380tcagctcact gcagcctccg cctcctgggt tcaagcgatt ctcctgcctc agcctcccga 1440gtagctggga ttataggcac ctgccaccat gcctggctaa tttttttgta tttttagtag 1500ggatggggtt tcaccatgtt 152028961DNAArtificial Sequencesequence of STAR28 28aggaggttat tcctgagcaa atggccagcc tagtgaactg gataaatgcc catgtaagat 60ctgtttaccc tgagaagggc atttcctaac tctccctata aaatgccaag tggagcaccc 120cagatgaaat agctgatatg ctttctatac aagccatcta ggactggctt tatcatgacc 180aggatattca cccactgaat atggctatta cccaagttat ggtaaatgct gtagttaagg 240gggtcccttc cacatggaca ccccaggtta taaccagaaa gggttcccaa tctagactcc 300aagagagggt tcttagacct catgcaagaa agaacttggg gcaagtacat aaagtgaaag 360caagtttatt aagaaagtaa agaaacaaaa aaatggctac tccataagca aagttatttc 420tcacttatat gattaataag agatggatta ttcatgagtt ttctgggaaa ggggtgggca 480attcctggaa ctgagggttc ctcccacttt tagaccatat agggtatctt cctgatattg 540ccatggcatt tgtaaactgt catggcactg atgggagtgt cttttagcat tctaatgcat 600tataattagc atataatgag cagtgaggat gaccagaggt cacttctgtt gccatattgg 660tttcagtggg gtttggttgg cttttttttt tttttaacca caacctgttt tttatttatt 720tatttattta tttatttatt tatatttttt attttttttt agatggagtc ttgctctgtc 780acccaggtta gagtgcagtg gcaccatctc ggctcactgc aagctctgcc tccttggttc 840acgccattct gctgcctcag cctcccgagt agctgggact acaggtgcct gccaccatac 900ccggctaatt ttttctattt ttcagtagag acggggtttc accgtgttag ccaggatggt 960c 961292233DNAArtificial Sequencesequence of STAR29 29agcttggaca cttgctgatg ccactttgga tgttgaaggg ccgccctctc ccacaccgct 60ggccactttt aaatatgtcc cctctgccca gaagggcccc agaggagggg ctggtgaggg 120tgacaggagt tgactgctct cacagcaggg ggttccggag ggaccttttc tccccattgg 180gcagcataga aggacctaga agggccccct ccaagcccag ctgggcgtgc agggccagcg 240attcgatgcc ttcccctgac tcaggtggcg ctgtcctaaa ggtgtgtgtg ttttctgttc 300gccagggggt ggcggataca gtggagcatc gtgcccgaag tgtctgagcc cgtggtaagt 360ccctggaggg tgcacggtct cctccgactg tctccatcac gtcaggcctc acagcctgta 420ggcaccgctc ggggaagcct ctggatgagg ccatgtggtc atccccctgg agtcctggcc 480tggcctgaag aggaggggag gaggaggcca gcccctccct agccccaagg cctgcgaggc 540tgcaagcccg gccccacatt ctagtccagg cttggctgtg caagaagcag attgcctggc 600cctggccagg cttcccagct aggatgtggt atggcagggg tgggggacat tgaggggctg 660ctgtagcccc cacaacctcc ccaggtaggg tggtgaacag taggctggac aagtggacct 720gttcccatct gagattcaag agcccacctc tcggaggttg cagtgagccg agatccctcc 780actgcactcc agcctgggca acagagcaag actctgtctc aaaaaaacag aacaacgaca 840acaaaaaacc cacctctggc ccactgccta actttgtaaa taaagtttta ttggcacata 900gacacaccca ttcatttaca tactgctgcg gctgcttttg cattaccctt gagtagacga 960cagaccacgt ggccatggaa gccaaaaata tttactgtct ggccctttac agaagtctgc 1020tctagaggga gaccccggcc catggggcag gaccactggg cgtgggcaga agggaggcct 1080cggtgcctcc acgggcctag ttgggtatct cagtgcctgt ttcttgcatg gagcaccagg 1140ggtcagggca agtacctgga ggaggcaggc tgttgcccgc ccagcactgg gacccaggag 1200accttgagag gctcttaacg aatgggagac aagcaggacc agggctccca ttggctgggc 1260ctcagtttcc ctgcctgtaa gtgagggagg gcagctgtga aggtgaactg tgaggcagag 1320cctctgctca gccattgcag gggcggctct gccccactcc tgttgtgcac ccagagtgag 1380gggcacgggg tgagatgtca ccatcagccc ataggggtgt cctcctggtg ccaggtcccc 1440aagggatgtc ccatcccccc tggctgtgtg gggacagcag agtccctggg gctgggaggg 1500ctccacactg ttttgtcagt ggtttttctg aactgttaaa tttcagtgga aaattctctt 1560tcccctttta ctgaaggaac ctccaaagga agacctgact gtgtctgaga agttccagct 1620ggtgctggac gtcgcccaga aagcccaggt actgccacgg gcgccggcca ggggtgtgtc 1680tgcgccagcc atgggcacca gccaggggtg tgtctacgcc ggccaggggt aggtctccgc 1740cggcctccgc tgctgcctgg ggagggccgt gcctgacact gcaggcccgg tttgtccgcg 1800gtcagctgac ttgtagtcac cctgcccttg gatggtcgtt acagcaactc tggtggttgg 1860ggaaggggcc tcctgattca gcctctgcgg acggtgcgcg agggtggagc tcccctccct 1920ccccaccgcc cctggccagg gttgaacgcc cctgggaagg actcaggccc gggtctgctg 1980ttgctgtgag cgtggccacc tctgccctag accagagctg ggccttcccc ggcctaggag 2040cagccgggca ggaccacagg gctccgagtg acctcagggc tgcccgacct ggaggccctc 2100ctggcgtcgc ggtgtgactg acagcccagg agcgggggct gttgtaattg ctgtttctcc 2160ttcacacaga accttttcgg gaagatggct gacatcctgg agaagatcaa gaagtaagtc 2220ccgcccccca ccc 2233301851DNAArtificial Sequencesequence of STAR30 30cctcccctgg agccttcaga aggagcatgg cataggagtc ttgatttcag acgtctggtc 60cccagaatga tgggagaatg aatttctgtt atttaagcca cccaacctgt ggtgctttgt 120tatagcagcc tcaggaaact aacacactgc acgtgcccac tattcccttt tccagtatct 180ttcaggactt gctggcttcc tttgttctgg cgtacaccca tgcatggccc cattccccac 240ttcctaaaac aacaaccctg acttagtctg tttgggctgc tagaacaaaa tactatagac 300tgggtgactt ataaacaaca gaaattcatt tctcacattc tggaggctgg gaagtccaat 360atcgaggcac catcacattt ggtctctgct gaggccccct tcctagctcc tcactgtgtc 420cttacatggc agaaggggca aggcagctct ctggggtccc ttttcaaggc cacaaatccc 480attcattagg gctgatgact tcatgactta atcacctcct aatggcccca cctcctaatc 540gcattgggcg ttaggattca acataaattt tggggggaca cacatattca gaccatagca 600aaccccaaca ataaaaaacc ttcactttaa ggttccaaat ggactggcag ttaaatcatg 660ttcatattta cataaaagaa ggagtaagtc aacaaattga taaacgcgtg gagatttgtt 720cggatggatg ttcaccaaaa tgctggcctt aaagagtgag atgggaaatg ggaactatta 780cattcttctt catacttttt ggtactgcct gcattgttaa aaaaaaaaaa aaagagcaca 840gagcattttt acaatcagga aaaaaacaat gaggttatct tcattctgga aaaaaatgga 900aaatgaaaca gtggagtcac atcatggaaa atgcttatgg tacaatttca tgtgacataa 960aacaatagaa tagaggacct gttttatgac taaagcactg taaaaatgac aggcctggaa 1020ggagagatga aaaccactca tttgttaagg tagtcaggtg gcaggtgatt tctcttcttt 1080tgaaaatttc cattttcatt atatcgcagt ttgtgcattt actaaaactt tcggttggta 1140cacatgcata aatagataga taaataagta gatagatgat agataaatag acggtaggta 1200gatagataga tagatatgag aaataagtcc cctgtacttg gccttgcagc cataactagt 1260cattcccctt cctctgtcca ttgctatgcc tgatggacaa ggcagtctgt gccctctggc 1320cccaattcca atgtgccctc tgctcctggc tgttagtccc tttccacccc aatacaattg 1380ctccgaggtc acttctaagt gtgaagcccc cagatcagat ggcttcttct gtgtccttac 1440cttacccaat ttctaattat aactaaaaca caatgaggct ctagtaaaat accatgagac 1500ttcaggccct ctgtataact tcactcattt aaacctaaca aggaaaacct accatgaatc 1560cgaggcacag agcagctaag gaactcacca aggtcacgca gctattggtg atggaaccat 1620gagtcaagct tcacagcctg ttggctctag aatagggttt cccaacctca gcactgtgga 1680cattttcagg ctggataatt ctctgttgtg gggggctgtt ctgtgccttg taggatatta 1740ggagcatctc tggcctctac ccactagacg cagcagcact cccatgccca gttgtgacaa 1800caagcaatgt ctcccaccat tgccaagtgt cccctgggtg gaaatgcacc c 1851311701DNAArtificial Sequencesequence of STAR31 31cacccgcctt ggccccccag agtgctggga ttacaagtgt aaaccaccat tcctggctag 60atttaatttt ttaaaaaata aagagaagta ggaatagttc attttaggga gagcccctta 120actgggacag gggcaggaca ggggtgaggc ttcccttant tcaagctcac ctcaaaccca 180cccaggactg tgtgtcacat tctccaataa aggaaaggtt gctgcccccg cctgtgagtg 240ctgcagtgga gggtagaggg ccgtgggcag agtgcttcat ggactgctca tcaagaaagg 300cttcatgaca atcggcccag ctgctgtcat cccacattct acttccagct aggagaaggc 360ggcttgccca cagtcaccca gccggcaagt gtcacccctg ggttggaccc agagctatga 420tcctgcccag gggtccagct gagaatcagg cccacgttct aggcagaggg gctcacctac 480tgggactcca gtagctgtag tgcatggagg catcatggct gcagcagcct ggacctggtc 540tcacactggc tgtccctgtg ggcaggccat cctcaatgcc aggtcaggcc caagcatgta 600tcccagacaa tgacaatggg gtggaatcct ctcttgtccc agaagccact cctcactgtt 660ctacctgagg aaggcagggg catggtggaa tcctgaagcc tgctgtgagg gtctccagcg 720aacttgcaca tggtcagccc tgccttctcc tccctgaact agattgagcg agagcaagaa 780ggacattgaa ccagcaccca aagaattttg gggaacggcc tctcatccag gtcaggctca 840cctccttttt aaaatttaat taattaatta attaattttt ttttagagac agagtcttac 900tgtgtggccc aggctgtagt gcagtggcac aatcatagtt cactgcagcc tcaaactccc 960cacctcagcc tctggattag ctgagactac aggtgcacca ccaccacacc cagctaatat 1020ttttattttt gtagagagag ggtttcacca tcttgcccag gctggtctca aactcctggg 1080ctcaagtgat cccgcccagg tctgaaagcc cccaggctgg cctcagactg tggggttttc 1140catgcagcca cccgagggcg cccccaagcc agttcatctc ggagtccagg cctggccctg 1200ggagacagag tgaaaccagt ggtttttatg aacttaactt agagtttaaa agatttctac 1260tcgatcactt gtcaagatgc gccctctctg gggagaaggg aacgtgactg gattccctca 1320ctgttgtatc ttgaataaac gctgctgctt catcctgtgg gggccgtggc cctgtccctg 1380tgtgggtggg gcctcttcca tttccctgac ttagaaacca cagtccacct agaacagggt 1440ttgagaggct tagtcagcac tgggtagcgt tttgactcca ttctcggctt tcttcttttt 1500ctttccagga tttttgtgca gaaatggttc ttttgttgcc gtgttagtcc tccttggaag 1560gcagctcaga aggcccgtga aatgtcgggg gacaggaccc ccagggaggg aaccccaggc 1620tacgcacttt agggttcgtt ctccagggag ggcgacctga cccccgnatc cgtcggngcg 1680cgnngnnacn aannnnttcc c 170132771DNAArtificial Sequencesequence of STAR32 32gatcacacag cttgtatgtg ggagctagga ttggaacccc agaagtctgg ccccaggttc 60atgctctcac ccactgcata caatggcctc tcataaatca atccagtata aaacattaga 120atctgcttta aaaccataga attagtagcg taagtaataa atgcagagac catgcagtga 180atggcattcc tggaaaaagc ccccagaagg aattttaaat cagctttcgt ctaatcttga 240gcagctagtt agcaaatatg agaatacagt tgttcccaga taatgcttta tgtctgacca 300tcttaaactg gcgctgtttt tcaaaaactt aaaaacaaaa tccatgactc ttttaattat 360aaaagtgata catgtctact tgggaggctg aggtggtggg aggatggctt gagtttgagg 420ctgcagtatg ctactatcat gcctataaat agccgctgca ttccagcttg ggcaacatac 480ccaggcccta tctcaaaaaa ataaaaagta atacatctac attgaagaaa attaatttta 540ttgggttttt ttgcattttt attatacaca gcacacacag cacatatgaa aaaatgggta 600tgaactcagg cattcaactg gaagaacagt actaaatcaa tgtccatgta gtcagcgtga 660ctgaggttgg tttgtttttt cttttttctt ctcttctctt ctcttttctt tttttttgag 720acggagcttt gctctttttg cccaggcttg attgcaatgg cgtgatctca g 771331368DNAArtificial Sequencesequence of STAR33 33gcttttatcc tccattcaca gctagcctgg cccccagagt acccaattct ccctaaaaaa 60cggtcatgct gtatagatgt gtgtggcttg gtagtgctaa agtggccaca tacagagctc 120tgacaccaaa cctcaggacc atgttcatgc cttctcactg agttctggct tgttcgtgac 180acattatgac attatgatta tgatgacttg tgagagcctc agtcttctat agcactttta 240gaatgcttta taaaaaccat ggggatgtca ttatattcta acctgttagc acttctgttc 300gtattaccca tcacatccca acatcaattc tcatatatgc aggtacctct tgtcacgcgc 360gtccatgtaa ggagaccaca aaacaggctt tgtttgagca acaaggtttt tatttcacct 420gggtgcaggt gggctgagtc tgaaaagaga gtcagtgaag ggagacaggg gtgggtccac 480tttataagat ttgggtaggt agtggaaaat tacaatcaaa gggggttgtt ctctggctgg 540ccagggtggg ggtcacaagg tgctcagtgg gagagccttt gagccaggat gagccagaag 600gaatttcaca aggtaatgtc atcagttaag gcagggactg gccattttca cttcttttgt 660ggtggaatgt catcagttaa ggcaggaacc ggccattttc acttcttttg tgattcttca 720cttgcttcag gccatctgga cgtataggtg caggtcacag tcacagggga taagatggca 780atggcatagc ttgggctcag aggcctgaca cctctgagaa actaaagatt ataaaaatga 840tggtcgcttc tattgcaaat ctgtgtttat tgtcaagagg cacttatttg tcaattaaga 900acccagtggt agaatcgaat gtccgaatgt aaaacaaaat acaaaacctc tgtgtgtgtg 960tgtgtgtgag tgtgtgtgta tgtgtgtgtg tgtgtattag agaggaaaag cctgtatttg 1020gaggtgtgat tcttagattc taggttcttt cctgcccacc ccatatgcac ccaccccaca 1080aaagaacaaa caacaaatcc caggacatct tagcgcaaca tttcagtttg catattttac 1140atatttactt ttcttacata ttaaaaaact gaaaatttta tgaacacgct aagttagatt 1200ttaaattaag tttgttttta cactgaaaat aatttaatat ttgtgaagaa tactaataca 1260ttggtatatt tcattttctt aaaattctga acccctcttc

ccttatttcc ttttgacccg 1320attggtgtat tggtcatgtg actcatggat ttgccttaag gcaggagg 136834755DNAArtificial Sequencesequence of STAR34 34actgggcacc ctcctaggca ggggaatgtg agaactgccg ctgctctggg gctgggcgcc 60atgtcacagc aggagggagg acggtgttac accacgtggg aaggactcag ggtggtcagc 120cacaaagctg ctggtgatga ccaggggctt gtgtcttcac tctgcagccc taacacccag 180gctgggttcg ctaggctcca tcctgggggt gcagaccctg agagtgatgc cagtgggagc 240ctcccgcccc tccccttcct cgaaggccca ggggtcaaac agtgtagact cagaggcctg 300agggcacatg tttatttagc agacaaggtg gggctccatc agcggggtgg cctggggagc 360agctgcatgg gtggcactgt ggggagggtc tcccagctcc ctcaatggtg ttcgggctgg 420tgcggcagct ggcggcaccc tggacagagg tggatatgag ggtgatgggt ggggaaatgg 480gaggcacccg agatggggac agcagaataa agacagcagc agtgctgggg ggcaggggga 540tgagcaaagg caggcccaag acccccagcc cactgcaccc tggcctccca caagccccct 600cgcagccgcc cagccacact cactgtgcac tcagccgtcg atacactggt ctgttaggga 660gaaagtccgt cagaacaggc agctgtgtgt gtgtgtgcgt gtatgagtgt gtgtgtgtga 720tccctgactg ccaggtcctc tgcactgccc ctggg 755351193DNAArtificial Sequencesequence of STAR35 35cgacttggtg atgcgggctc ttttttggtt ccatatgaac tttaaagtag tcttttccaa 60ttctgtgaag aaagtcattg gtaggttgat ggggatggca ttgaatctgt aaattacctt 120gggcagtatg gccattttca caatgttgat tcttcctatc catgatgatg gaatgttctt 180ccattagttt gtatcctctt ttatttcctt gagcagtggt ttgtagttct ccttgaagag 240gtccttcaca tcccttgtaa gttggattcc taggtatttt attctctttg aagcaaattg 300tgaatgggag tncactcacg atttggctct ctgtttgtct gctgggtgta taaanaatgt 360ngtgatnttn gtacattgat ttngtatccn tgagacttng ctgaatttgc ttnatcngct 420tnngggaacc ttttgggctg aaacnatggg attttctaaa tatacaatca tgtcgtctgc 480aaacagggaa caatttgact tcctcttttc ctaattgaat acactttatc tccttctcct 540gcctaattgc cctgggcaaa acttccaaca ctatgntngn aataggagnt ggtgagagag 600ggcatccctg ttcttgttgc cagnttttca aagggaatgc ttccagtttt ggcccattca 660gtatgatatg ggctgtgggt ngtgtcataa atagctctta tnattttgaa atgtgtccca 720tcaataccta atttattgaa agtttttagc atgaangcat ngttgaattt ggtcaaaggc 780tttttctgca tctatggaaa taatcatgtg gtttttgtct ttggctcntg tttatatgct 840ggatnacatt tattgatttg tgtatatnga acccagcctn ncatcccagg gatgaagccc 900acttgatcca agcttggcgc gcngnctagc tcgaggcagg caaaagtatg caaagcatgc 960atctcaatta gtcagcaccc atagtccgcc cctacctccg cccatccgcc cctaactcng 1020nccgttcgcc cattctcgcc catggctgac taatnttttt annatccaag cggngccgcc 1080ctgcttganc attcagagtn nagagnnttg gaggccnagc cttgcaaaac tccggacngn 1140ttctnnggat tgaccccnnt taaatatttg gttttttgtn ttttcanngg nga 1193361712DNAArtificial Sequencesequence of STAR36 36gatcccatcc ttagcctcat cgatacctcc tgctcacctg tcagtgcctc tggagtgtgt 60gtctagccca ggcccatccc ctggaactca ggggactcag gactagtggg catgtacact 120tggcctcagg ggactcagga ttagtgagcc ccacatgtac acttggcctc agtggactca 180ggactagtga gccccacatg tacacttggc ctcaggggac tcaggattag tgagccccca 240catgtacact tggcctcagg ggactcagga ttagtgagcc ccacatgtac acttggcctc 300aggggactca ggactagtga gccccacatg tacacttggc ctcaggggac tcagaactag 360tgagccccac atgtacactt ggcttcaggg gactcaggat tagtgagccc cacatgtaca 420cttggacacg tgaaccacat cgatgtgctg cagagctcag ccctctgcag atgaaatgtg 480gtcatggcat tccttcacag tggcacccct cgttccctcc ccacctcatc tcccattctt 540gtctgtcttc agcacctgcc atgtccagcc ggcagattcc accgcagcat cttctgcagc 600acccccgacc acacacctcc ccagcgcctg cttggccctc cagcccagct cccgcctttc 660ttccttgggg aagctccctg gacagacacc ccctcctccc agccatggct ttttcctgct 720ctgccccacg cgggaccctg ccctggatgt gctacaatag acacatcaga tacagtcctt 780cctcagcagc cggcagaccc agggtggact gctcggggcc tgcctgtgag gtcacacagg 840tgtcgttaac ttgccatctc agcaactagt gaatatgggc agatgctacc ttccttccgg 900ttccctggtg agaggtactg gtggatgtcc tgtgttgccg gccacctttt gtccctggat 960gccatttatt tttttccaca aatatttccc aggtctcttc tgtgtgcaag gtattagggc 1020tgcagcgggg gccaggccac agatctctgt cctgagaaga cttggattct agtgcaggag 1080actgaagtgt atcacaccaa tcagtgtaaa ttgttaactg ccacaaggag aaaggccagg 1140aaggagtggg gcatggtggt gttctagtgt tacaagaaga agccagggag ggcttcctgg 1200atgaagtggc atctgacctg ggatctggag gaggagaaaa atgtcccaaa agagcagaga 1260gcccacccta ggctctgcac caggaggcaa cttgctgggc ttatggaatt cagagggcaa 1320gtgataagca gaaagtcctt gggggccaca attaggattt ctgtcttcta aagggcctct 1380gccctctgct gtgtgacctt gggcaagtta cttcacctct agtgctttgg ttgcctcatc 1440tgtaaagtgg tgaggataat gctatcacac tggttgagaa ttgaagtaat tattgctgca 1500aagggcttat aagggtgtct aatactagta ctagtaggta cttcatgtgt cttgacaatt 1560ttaatcatta ttattttgtc atcaccgtca ctcttccagg ggactaatgt ccctgctgtt 1620ctgtccaaat taaacattgt ttatccctgt gggcatctgg cgaggtggct aggaaagcct 1680ggagctgttt cctgttgacg tgccagacta gt 1712371321DNAArtificial Sequencesequence of STAR37 37atctctctct gccaaagcaa cagcggtccc tgccccaacc agactacccc actcagtggg 60gttacggatg ctgctccagc atcctaacac tgcccagctg gtgcctgcct gtgctcaccc 120acaaccccca ggccggcctt ccctgcagcc tgggcttggc caccttggcc tgattgagca 180ctgaggcctc ctgggcaccc agccccatca ctgcacctgc tgcttccagc cccaccccac 240cggctcaggg gttcttccca gcggcgctga tcatgaagtc aacatgcacg caagtcgtct 300caggaaactt tttaatgaaa gtgtcggcca cggtggtgtg taggtggctg agctcagatt 360gcagctgcta agacaccagc cacttaccaa gagaaagcca ggctgcttca aacccagggc 420cggaggcaaa aaagcatcac ttccagccgg ggagtctgga agccacgcct tgtgggaggt 480cacactggca tctaggcctt cgcctgcact gcagaaggag agccgggtcc ccctcctgga 540gaacgctgcg ttccccagcc ccacaccggc tttgccacca cacaggctgt tgaggcagga 600ggcgggtaag acgtagctgt agacccaaag caaccaccag ccctgggacc ctgcgggaga 660ggagcacttt tagaacatgg aaaaatgtgg tcatcccatc attagacagc acacatccta 720cataaataaa aagtcgtatg gggaaggagg ttggggaggg aataaaaaat tggcacagac 780attgatagac tggtttccag tttcaaggta acagatgcac atcatgagac cagaggaggc 840agagacaagg gctgaatttg gcttttctaa gcaacatgtg ttcctgcgca gggctgaatg 900gtcgctgaga cagagatgga agccaggaca agggagccca ccgggcccag ataggtacag 960agagcagagg ctcctgttct gtcctcgcca cccatgaggg tgacactgct tgtaaatggt 1020ggctgtgctc tcccagcaag aaaaaagcac aactaaatcc acactgcaca cagacgcaga 1080cagaaagcct tcaagtggct ctgttttctg ctccctgcct tgccaggtcc acaagcagag 1140aggagtgtca ggcacatggc cccgctgtca ggctccccag tgagctgtag gctcagcagg 1200agctgcccac tgacacacag gggacaccca ctcctgccac cttgggagcg gttgccagac 1260agagccgcac tgggtgctgg tgtcatccag ggaccccaca cacttcctta aatgtgatcc 1320t 1321381445DNAArtificial Sequencesequence of STAR38 38gatctatggg agtagcttcc ttagtgagct ttcccttcaa atactttgca accaggtaga 60gaattttgga gtgaaggttt tgttcttcgt ttcttcacaa tatggatatg catcttcttt 120tgaaaatgtt aaagtaaatt acctctcttt tcagatactg tcttcatgcg aacttggtat 180cctgtttcca tcccagcctt ctataaccca gtaacatctt ttttgaaacc agtgggtgag 240aaagacacct ggtcaggaac gcggaccaca ggacaactca ggctcaccca cggcatcaga 300ctaaaggcaa acaaggactc tgtataaagt accggtggca tgtgtatnag tggagatgca 360gcctgtgctc tgcagacagg gagtcacaca gacacttttc tataatttct taagtgcttt 420gaatgttcaa gtagaaagtc taacattaaa tttgattgaa caattgtata ttcatggaat 480attttggaac ggaataccaa aaaatggcaa tagtggttct ttctggatgg aagacaaact 540tttcttgttt aaaataaatt ttattttata tatttgaggt tgaccacatg accttaagga 600tacatataga cagtaaactg gttactacag tgaagcaaat taacatatct accatcgtac 660atagttacat ttttttgtgt gacaggaaca gctaaaatct acgtatttaa caaaaatcct 720aaagacaata catttttatt aactatagcc ctcatgatgt acattagatc gtgtggttgt 780ttcttccgtc cccgccacgc cttcctcctg ggatggggat tcattcccta gcaggtgtcg 840gagaactggc gcccttgcag ggtaggtgcc ccggagcctg aggcgggnac tttaanatca 900gacgcttggg ggccggctgg gaaaaactgg cggaaaatat tataactgna ctctcaatgc 960cagctgttgt agaagctcct gggacaagcc gtggaagtcc cctcaggagg cttccgcgat 1020gtcctaggtg gctgctccgc ccgccacggt catttccatt gactcacacg cgccgcctgg 1080aggaggaggc tgcgctggac acgccggtgg cgcctttgcc tgggggagcg cagcctggag 1140ctctggcggc agcgctggga gcggggcctc ggaggctggg cctggggacc caaggttggg 1200cggggcgcag gaggtgggct cagggttctc cagagaatcc ccatgagctg acccgcaggg 1260cggccgggcc agtaggcacc gggcccccgc ggtgacctgc ggacccgaag ctggagcagc 1320cactgcaaat gctgcgctga ccccaaatgc tgtgtccttt aaatgtttta attaagaata 1380attaataggt ccgggtgtgg aggctcaagc cttaatcccc agcacctggc gaggccgagg 1440aggga 1445392331DNAArtificial Sequencesequence of STAR39 39tcactgcaac ctccacctcc caggttcaag tgattctcct gcctcggcct cccgagtagc 60tgggactaca ggtgcatgac accgcacctg gctagttttt gtatttttag tagagacagg 120gtttcactat gttggccagg ttggtctcga actcctgacc ttgtgatccg cccacctcgg 180cctcccaaag tgctgggatt acagagtgag ccactgcgcc tggcctgcac cccttactat 240tatatgcttt gcattttctt ttagatttga agaacctcat tataaactct agcactaatc 300ttatgtcagt taaatgcata gcaaatatct cctgacgtgg gagaatatat atttgcaagt 360cttcttgtga acatatgttt tcagttctag ggagccagac gcctatgagt gaaaagccta 420gtcatcgtgg agaagtgcat tcaactttgt aagaaactgc caaaccttta ttcataatgg 480ttgtataaat tttacattac caccaataat gtatgagagt tccagttgct tcacatcctc 540accagcattt tgttttgtct gtcttttttc ctttggttat tctagtgggc ataagatata 600atagtatccc ttgtggttta atgtaaattc cactgaagac taataacatt tgcatatttc 660taattaataa gcctttttaa gtgacttttc aagtctttgc tcatttttat tagatatttg 720ccttcttatt attgatttga aagaattata tttatatgct tatattctgg ttataagccc 780tttgtcatta ttttccaaaa caatatttgg ttgtttctgt actactttcc ttgctccttt 840gaattgactt ggtgccttgg ccaaaaatca attgaccaca tacatgtggg tgcatctcca 900gactaccaca ttccgtttat ctatttgtct ctccttgtgt caataacact ctgtcttgat 960aatggtaagt tttgagatca ggttgtgtaa gtcctcctaa tttttcctgg gttttcaata 1020ttgctttgct ttttaaaaat tttgtatttt catttacatt ttaaaataaa cttgttagtg 1080ggattttgat tggcattgca ctgaactcgt ggatcaattt ggggagattg gacattctta 1140tatatggatc ccgtggtcat caactttaag aactctttct catccattag taactcaatc 1200taggttcaga tgctactcgt tttctgctca gtctgtgtct gagcccctta tgctcttcat 1260tttgtcatcc aattaacctc agctttgcat caatactatt tcttgctttg gtgcctgtta 1320cctctcctct aatcaccaat ccacaactta cctccaaatt cagggcttgt ctcattcttc 1380ccaggaggag tgctgctcag tctatctact tagtattata atttctctgg cttggtatca 1440aggcactccc atttccggct tccatgagat gtctcagagg gcatgctgcc cggtgtagct 1500gcatggtcaa gcttcttcat atctcttgcc tcatcactta aactcactat tttgtactcc 1560tgcttcagct atagggagct actgttagtt tcttgaagac atatgctctc tctctctctc 1620acatctggac ctgagcacat cctgttactg ctgcttgaaa caatgtgatc cccaggcaca 1680caccattagc ttagaagcct cccctgattc ttcaaggctg gttgagtccc ttctctgtgc 1740tctcatgaca acagttggca attcctcgtt gcagcaccta gcccatgatg ctctttggag 1800gcagagactg agtctttctc actattgaat ttccagcatt catcacagag cctggcatat 1860ataaagccct ccatcatatg tattaagtga atggataaat gaaaaaaagt tatatatatg 1920tacatatatg tgtatatatg tatatgtata tatgtgtata tatgtgtgta tatgtgtgtg 1980tatatatgta catatatatg tatctatgta catatatgta tatatgtata tatatgtgtg 2040tgtatatgtg tgtgtgtatg tatatatatt acaatgaaat actattcagc cttaaaaagg 2100cagggaatcc tgtcatttaa cacaatatgg ataaacctag aggactctaa aggcaaatac 2160cacatgttct cactcacaaa atctaaacaa gttgaactcc tacaagtaga gagtaggatg 2220atggttacca agggctgggg gacgggagag gatggggaaa gcatagctgt ccatcaaagg 2280gtagaaagtt tcatttagac aagaggaatc agctttagtg atctatttca c 2331401071DNAArtificial Sequencesequence of STAR40 40gctgtgattc aaactgtcag cgagataagg cagcagatca agaaagcact ccgggctcca 60gaaggagcct tccaggccag ctttgagcat aagctgctga tgagcagtga gtgtcttgag 120tagtgttcag ggcagcatgt taccattcat gcttgacttc tagccagtgt gacgagaggc 180tggagtcagg tctctagaga gttgagcagc tccagcctta gatctcccag tcttatgcgg 240tgtgcccatt cgctttgtgt ctgcagtccc ctggccacac ccagtaacag ttctgggatc 300tatgggagta gcttccttag tgagctttcc cttcaaatac tttgcaacca ggtagagaat 360tttggagtga aggttttgtt cttcgtttct tcacaatatg gatatgcatc ttcttttgaa 420aatgttaaag taaattacct ctcttttcag atactgtctt catgcgaact tggtatcctg 480tttccatccc agccttctat aacccagtaa catctttttt gaaaccagtg ggtgagaaag 540acacctggtc aggaacgcgg accacaggac aactcaggct cacccacggc atcagactaa 600aggcaaacaa ggactctgta taaagtaccg gtggcatgtg tattagtgga gatgcagcct 660gtgctctgca gacagggagt cacacagaca cttttctata atttcttaag tgctttgaat 720gttcaagtag aaagtctaac attaaatttg attgaacaat tgtatattca tggaatattt 780tggaacggaa taccaaaaaa tggcaatagt ggttctttct ggatggaaga caaacttttc 840ttgtttaaaa taaattttat tttatatatt tgaggttgac cacatgacct taaggataca 900tatagacagt aaactggtta ctacagtgaa gcaaattaac atatctacca tcgtacatag 960ttacattttt ttgtgtgaca ggaacagcta aaatctacgt atttaacaaa aatcctaaag 1020acaatacatt tttattaact atagccctca tgatgtacat tagatctcta a 1071411135DNAArtificial Sequencesequence of STAR41 41tgctcttgtt gcccaggctg cagtgcaatg gcgctgtctc ggctcatcgc aacctccgcc 60tcccagattc aagtgattct cctgcctcac cctcccaagt agctgggatt accagtatgc 120agcaacacgc ccggctaatt ttgtatttgt aatagagacg gggtttcttc atgttggtca 180ggctggtctc aaattcctgc cctcaggtga tctgcccacc ttggcctccc aaagtgctgg 240gattacaggc atgagccact gtgcccggcc tgggctgggg cttttaaggg gactggaggg 300tgaggggctg gaaaattggg agagttgatt ggtggggcaa gggggatgta atcatcaggg 360tgtacaaact gcactcttgg tttagtcagc tcctcgtggg gtccttcgga gcagctcagt 420cagtagctcc atcagtatac aggacccaaa ggaatatctc aaagggaaaa cagcatttcc 480taaggttcaa gttgtgatct acggagcagt taggggaact acaatcttgt gacagggtct 540acatgcttct gaggcaatga gacaccaagc agctacgagg aagcagtcag agagcacgcc 600gacctagtga ctgatgctga tgtgctgcga gctgggttca ttttcatttc tcccctcccc 660ctgccctcat taattttgta aagtttatag ggaacatttc acccactctg ctgtggatcc 720ctgtcactta cggagtctgt catcttggct gtatgggctg tggcctctgc ggtgcccatt 780ctcaggaggt gtgagaccca tgaggaccgg aggtggacaa ggctagagac cacacccccc 840cgctccatcc aatcatgttt tcctgggtgc ttggtttcta tgcaggctgc atgtccttag 900tccctgcatg ggaacagctc ctgtggtgag caggcccctg aggaaggcct tgagcgggaa 960tggagcctag gcttaggctg cctggtaaga gctggaggga accagccgag gcttgtgcta 1020cttttttttc cagaatgaaa tacgtgactg atgttggtgt cctgcagcgc cacgtttccc 1080gccacaacca ccggaacgag gatgaggaga acacactctc cgtggactgc acacg 113542735DNAArtificial Sequencesequence of STAR42 42aagggtgaga tcactaggga gggaggaagg agctataaaa gaaagaggtc actcatcaca 60tcttacacac tttttaaaac cttggttttt taatgtccgt gttcctcatt agcagtaagc 120cctgtggaag caggagtctt tctcattgac caccatgaca agaccctatt tatgaaacat 180aatagacaca caaatgttta tcggatattt attgaaatat aggaattttt cccctcacac 240ctcatgacca cattctggta cattgtatga atgaatatac cataatttta cctatggctg 300tatatttagg tcttttcgtg caggctataa aaatatgtat gggccggtca cagtgactta 360cgcccgtagt cccagaactt tgggaggccg aggcgggtgg atcacctgag gtcgggagtt 420caaaaccagc ctgaccaaca tggagaaacc ccgtctctgc taaaaataca aaaattaact 480ggacacggtg gcgtatgcct gtaatcccag ctactcggga agctgaggca ggagaactgc 540ttgaacccag gaggcggagg ttgtggtgag tcgagattgc gccattgcac tccagcctgg 600gcaacaagag cgaaattcca tctcaaaaaa aagaaaaaag tatgactgta tttagagtag 660tatgtggatt tgaaaaatta ataagtgttg ccaacttacc ttagggttta taccatttat 720gagggtgtcg gtttc 735431227DNAArtificial Sequencesequence of STAR43 43caaatagatc tacacaaaac aagataatgt ctgcccattt ttccaaagat aatgtggtga 60agtgggtaga gagaaatgca tccattctcc ccacccaacc tctgctaaat tgtccatgtc 120acagtactga gaccaggggg cttattccca gcgggcagaa tgtgcaccaa gcacctcttg 180tctcaatttg cagtctaggc cctgctattt gatggtgtga aggcttgcac ctggcatgga 240aggtccgttt tgtacttctt gctttagcag ttcaaagagc agggagagct gcgagggcct 300ctgcagcttc agatggatgt ggtcagcttg ttggaggcgc cttctgtggt ccattatctc 360cagcccccct gcggtgttgc tgtttgcttg gcttgtctgg ctctccatgc cttgttggct 420ccaaaatgtc atcatgctgc accccaggaa gaatgtgcag gcccatctct tttatgtgct 480ttgggctatt ttgattcccc gttgggtata ttccctaggt aagacccaga agacacagga 540ggtagttgct ttgggagagt ttggacctat gggtatgagg taatagacac agtatcttct 600ctttcatttg gtgagactgt tagctctggc cgcggactga attccacaca gctcacttgg 660gaaaacttta ttccaaaaca tagtcacatt gaacattgtg gagaatgagg gacagagaag 720aggccctaga tttgtacatc tgggtgttat gtctataaat agaatgcttt ggtggtcaac 780tagacttgtt catgttgaca tttagtcttg ccttttcggt ggtgatttaa aaattatgta 840tatcttgttt ggaatatagt ggagctatgg tgtggcattt tcatctggct ttttgtttag 900ctcagcccgt cctgttatgg gcagccttga agctcagtag ctaatgaaga ggtatcctca 960ctccctccag agagcggtcc cctcacggct cattgagagt ttgtcagcac cttgaaatga 1020gtttaaactt gtttattttt aaaacattct tggttatgaa tgtgcctata ttgaattact 1080gaacaacctt atggttgtga agaattgatt tggtgctaag gtgtataaat ttcaggacca 1140gtgtctctga agagttcatt tagcatgaag tcagcctgtg gcaggttggg tggagccagg 1200gaacaatgga gaagctttca tgggtgg 1227441586DNAArtificial Sequencesequence of STAR44 44tgagttgggg tcctaagcca gaagttaact atgctttcat atattcttgc aagtagaagt 60acagtgttgg tgtaaattcc ccttagatgg atagctaagc ccagaggaaa taatggtaat 120tggaaccata tgaccgtatg caattcatgt gcatatttat atcaagaaaa gaacattata 180ggtcgggtga gaccctattt tgttctgaca atgtcatctg tatttacatg tctgtttcgg 240gagtttggat gtcaagggat tctgtgctgg attgtaaagc atgtgcttct gcttgatgta 300gctactcaat tttgtattct tgactaataa agtcataaac ataattcaac ctctgtgtgc 360gtgctctcct tccattaatt tatactttag caaaaagtat tgaatgtgtg tgttatgtaa 420caatttccta taaattatat taaatgattt attagcttta ttcaataaag ttttaagtgt 480tttcttctat gactacatta tttgttaaca agaaatttct ttaactgaaa acttcaagga 540agactatctg ggtaactctt tcaaaaagaa ttgtccctgt attttgggat tgaatatatt 600aatttcttgt actgttttaa cagcacataa ttttacaaga caagccactt tttcaaagcc 660tgcttctcct cccattttcc ctatctctgt gattgacacc tccaacccct gtagcctgcc 720tctgctctct cttaaccagt cctactgata ctacttccta agtatttttc agccctgtcc 780ttcctctcca tcatgatgga ttcacttcca gttgaaatcc ttatggtacc ctccctggat 840tatggcagta atcagagagc tggtctcctt aactcaggat tcacttcttc tcatctgttg 900ttcacagtga catcagaaag atattttaaa atgatgaact agaattaatt atataaaaca 960cacatacaca cataaataat acttaaattt ttcaatgatg ttccaattat gtaaaatata 1020atataggagg cactttatgt tctggcctca atctttcaat tcaaacttat ctcctgccac 1080tatctccttt gaacattgta ttccagctac tttagaataa taataataca taatattcat 1140agagcccttc ctgggttcct atcaccgtac aaaatacttc acatataaca tttaatcttt 1200gacaacttta ttaggcatgc acaattatta tctatctata tatctatatc tatatatata

1260aaatctatat tttatagata agaaaataga gggtaaaaac ttgccaaaat tacaaagctt 1320agaagtgtag cagttgggat ttgaatctag gcatcctgcc tctatagtct acagtggctt 1380tcttgtgcca aaagccttgc agttccctag acttaacatt tctcaaaatc tgtgtctttc 1440acatgctctt ccaattgtct ggaaaatctt tcccaacctc agtctaactg tggtactcat 1500gttcacccca caagaattga ctccatctgt cccctctcca tgaaaatttc tttgaatctc 1560agcactttgg gaggctgagg caggtg 1586451981DNAArtificial Sequencesequence of STAR45 45cacgccccag cgtgccctgg actactgctc cgcaggactc ctgttctgct gcaccctgga 60ctacggcacc agaggaccca gctcccgccg gcctgagcta tggcaccaga ggacccagct 120cccggcagcc tggactatgg caccagagga cccagccccc cgcttcctgg gctaaggcac 180agtaggaccc tgcctcatcg tgtactcctg ctcaggagga ccctcgcagg gcggcgcact 240ggactaagct actgaaggag ccccacccct gcctaaccct ggactaaggc actggagaac 300tcttgctccg cagagccacg gactcttgca caagagaacc tcagcccagc cgtgccctgg 360actgtggcac agtagggccc acaccacgcc atggactcct gtattggagg aagagtagtg 420ataaatgtcc aggtttacaa cttgaaaagt agcaatcaat gtgccacaat agatggatgt 480gatgtaaaat tataaatgat gaaaacatta tgtgtaattg cctagccaga acagttacac 540aagacaaaga cgtaaaagaa atccacatag ggaaggaaga ggtaagattg tttctgtttt 600ttgaaaatat aatcttaaga tagagaaaat cttaaagatt ccaccaaaat aaatggttat 660agctgatgaa gaaattcaat aaagttaata gttacaaaat caacatacaa atatcattat 720tgtttctatt aactaatgac aaactattac ctgaaaaata aaggcaattc aatttataat 780agaatcaaaa cagatatata aatatataaa agacaggagt aaatttaatc aaaaccataa 840aagatttaca tactgaaaac tatagcacat tgatgaaaaa aattaaaatg gcataaataa 900atggagaaac atccttcatt gatggattca aaaattagta ttgtaaaagt gtcaatgcta 960cccaaagcaa tctacagatt aaatgcaacc actatcaaat tccaatgtca ttcttcacag 1020aaatagaaaa attactgcta aaatttgtat ggaaccacaa aagacctgga ccaaccaaag 1080caatcttgaa caaaaagaac aaagctggag gcatcagact acctgactcc aaactctatt 1140acaaagctat aggaattaaa acagcatagc aatggcataa aaacagacat gtaaaacagt 1200acaaagggat atagaacctg taaataaatc cgtgtgtctg tggtcaattg attttttgat 1260aaaataacta aaaatacaca gtgaagaaag aaaattattt tcaataaatg gtgtagacaa 1320aactgactat ccacatacag aagaataaaa tttgactttt attttgctct ttatacaagc 1380atcaaatcaa aattaaagtt taaatgtaaa actactacaa ggaaatatag aaggagactg 1440tatgacattg gcctgagcta tgattttctg tagattattc caaaaggcaa caaaagcaaa 1500acacacaaat gagactgcat aaaacttaaa acttttccac aggaaaagaa gcaatgatag 1560aattaagaga acccacaaat gggataatat ttttaaacca tacatcaggt aaggggctca 1620tataataata tataagcaac tcaacctact caaaaataag aaaaaaacta tgcttattaa 1680aaaataagca aagaatcaga atagacattt cctacatcat acaaaaggcc aaccaggtac 1740atgaaaaaat cataaacatt cctaattatc agagaagtgc aaatcaatgc cacaatgaga 1800tatcacctca cacattttac tagggctatt ataaaaaaag atggaagata agtgttggtg 1860aggatgtgga gaaaaagaaa ccctgtacac tgttggtagg aatggaaatt agtacagcca 1920tcttggaaaa cagtacgaag ctttctcaag aaattataaa tttatttacc ctatgatcca 1980t 1981461859DNAArtificial Sequencesequence of STAR46 46attgtttttc tcgcccttct gcattttctg caaattctgt tgaatcattg cagttactta 60ggtttgcttc gtctccccca ttacaaacta cttactgggt ttttcaaccc tagttccctc 120atttttatga tttatgctca tttctttgta cacttcgtct tgctccatct cccaactcat 180ggcccctggc tttggattat tgttttggtc ttttattttt tgtcttcttc tacctcaaca 240cttatcttcc tctcccagtc tccggtaccc tatcaccaag gttgtcatta acctttcata 300ttattcctca ttatccatgt attcatttgc aaataagcgt atattaacaa aatcacaggt 360ttatggagat ataattcaca taccttaaaa ttcaggcttt taaagtgtac ctttcatgtg 420gtttttggta tattcacaaa gttatgcatt gatcaccacc atctgattcc ataacatgtt 480caatacctca aaaagaagtc tgtactcatt agtagtcatt tcacattcac cactccctct 540ggctctgggc agtcactgat ctttgtgtct ctatggattt gcctagtcta ggtattttta 600tgtaaatggc atcatacaac atgtgacctt ttgtttggct tttttcattt agcaaaatgt 660tatcaaggtc tgtccctgtt gtagcatgta ttagcacttc atttcttata tgctgaatga 720tatactttat ttgtccatca gttgttcatg ctttatttgt ccatcagttg atgaacattt 780gcgtttttgc cactttgggc tattaagaat aatgctactg tgaacaagtg tgtacaagtt 840cctctacaaa tttttgtgtg gacatatcct ttcagttctc tcaggtgtat atctgggaat 900tgaattgctg ggtcgtgtag tagctatgtt aaacactttg agaaactgct ataatgttct 960ccagagctgt accattttaa attctgtgta tgaggattcc acgttctcca cttcctcacc 1020agtgtatgga tttgggggta tactttttaa aaagtgggat taggctgggc acagtggctc 1080acacctgtaa tcccaacact tcaggaagct gaggtgggag gatcacttga gcctagtagt 1140ttgagaccag cctgggcaac atagggagac cctgtctcta caaaaaataa tttaaaataa 1200attagctggg cgttgtggca cacacctgta gtcccagcta catgggaggc tgaggtggaa 1260ggattccctg agcccagaag tttgaggttg cagtgagcca tgatggcagc actatactgt 1320agcctgggtg tcagagcaag actccgtttc agggaagaaa aaaaaaagtg ggatgatatt 1380tttgacactt ttcttcttgt tttcttaatt tcatacttct ggaaattcca ttaaattagc 1440tggtaccact ctaactcatt gtgtttcatg gctgcatagt aatattgcat aatataaata 1500taccattcat tcatcaaagt tagcagatat tgactgttag gtgccaggca ctgctctaag 1560cgttaaagaa aaacacacaa aaacttttgc attcttagag tttattttcc aatggagggg 1620gtggagggag gtaagaattt aggaaataaa ttaattacat atatagcata gggtttcacc 1680agtgagtgca gcttgaatcg ttggcagctt tcttagtagt ataaatacag tactaaagat 1740gaaattactc taaatggtgt tacttaaatt actggaatag gtattactat tagtcacttt 1800gcaggtgaaa gtggaaacac catcgtaaaa tgtaaaatag gaaacagctg gttaatgtt 1859471082DNAArtificial Sequencesequence of STAR47 47atcattagtc attagggaaa tgcaaatgaa aaacacaagc agccaccaat atacacctac 60taggatgatt taaaggaaaa taagtgtgaa gaaggacgta aagaaattgt aaccctgata 120cattgatggt agaaatggat aaagttgcag ccactgtgaa aaacagtctg cagtggctca 180gaaggttaaa tatagaaccc ctgttggacc caggaactct actcttaggc accccaaaga 240atagagaaca gaaatcaaac agatgtttgt atactaatgt ttgtagcatc acttttcaca 300ggagccaaaa ggtggaaata atccaaccat cagtgaacaa atgaatgtaa taaaagcaag 360gtggtctgca tgcaatgcta catcatccat ctgtaaaaaa cgaacatcat tttgatagat 420gatacaacat gggtggacat tgagaacatt atgcttagtg aaataagcca gacacaaaag 480gaatatattg tataattgta attacatgaa gtgcctagaa tagtcaaatt catacaagag 540aaagtgggat aggaatcacc atgggctgga aataggggga aggtgctata ctgcttattg 600tggacaaggt ttcgtaagaa atcatcaaaa ttgtgggtgt agatagtggt gttggttatg 660caaccctgtg aatatattga atgccatgga gtgcacactt tggttaaaag gttcaaatga 720taaatattgt gttatatata tttccccacg atagaaaaca cgcacagcca agcccacatg 780ccagtcttgt tagctgcctt cctttacctt caagagtggg ctgaagcttg tccaatcttt 840caaggttgct gaagactgta tgatggaagt catctgcatt gggaaagaaa ttaatggaga 900gaggagaaaa cttgagaatc cacactactc accctgcagg gccaagaact ctgtctccca 960tgctttgctg tcctgtctca gtatttcctg tgaccacctc ctttttcaac tgaagacttt 1020gtacctgaag gggttcccag gtttttcacc tcggcccttg tcaggactga tcctctcaac 1080ta 1082481242DNAArtificial Sequencesequence of STAR48 48atcatgtatt tgttttctga attaattctt agatacatta atgttttatg ttaccatgaa 60tgtgatatta taatataata tttttaattg gttgctactg tttataagaa tttcattttc 120tgtttacttt gccttcatat ctgaaaacct tgctgatttg attagtgcat ccacaaattt 180tcttggattt tctatgggta attacaaatc tccacacaat gaggttgcag tgagccaaga 240tcacaccact gtactccagc ctgggcgaca gagtgagaca ccatctcaca aaaacacata 300aacaaacaaa cagaaactcc acacaatgac aacgtatgtg ctttcttttt ttcttcctct 360ttctataata tttctttgtc ctatcttaac tgaactggcc agaaacccca ggacaatgat 420aaatacgagc agtgtcaaca gacatctcat tccctttcct agcttttata aaaataacga 480ttatgcttca acattacata tggtggtgtc gatggttttg ttatagataa gcttatcagg 540ttaagaaatt tgtctgcgtt tcctagtttg gtataaagat tttaatataa atgaatgttg 600tattttatca tcttattttt ttcctacatc tgctaaggta atcctgtgtt ttcccctttt 660caatctccta atgtggtgaa tgacattaaa ataccttcta ttgttaaaat attcttgcaa 720cgctgtatag aaccaatgcc tttattctgt attgctgatg gatttttgaa aaatatgtag 780gtggacttag ttttctaagg ggaatagaat ttctaatata tttaaaatat tttgcatgta 840tgttctgaag gacattggtg tgtcatttct ataccatctg gctactagag gagccgactg 900aaagtcacac tgccggagga ggggagaggt gctcttccgt ttctggtgtc tgtagccatc 960tccagtggta gctgcagtga taataatgct gcagtgccga cagttctgga aggagcaaca 1020acagtgattt cagcagcagc agtattgcgg gatccccacg atggagcaag ggaaataatt 1080ctggaagcaa tgacaatatc agctgtggct atagcagctg agatgtgagt tctcacggtg 1140gcagcttcaa ggacagtagt gatggtccaa tggcgcccag acctagaaat gcacatttcc 1200tcagcaccgg ctccagatgc tgagcttgga cagctgacgc ct 1242491015DNAArtificial Sequencesequence of STAR49 49aaaccagaaa cccaaaacaa tgggagtgac atgctaaaac cagaaaccca aaacaatggg 60agggtcctgc taaaccagaa acccaaaaca atgggagtga agtgctaaaa ccagaaaccc 120aaaacaatgg gagtgtcctg ctacaccaga aacccaaaac gatgggagtg acgtgataaa 180accagacacc caaaacaatg ggagtgacgt gctaaaccag aaacccaaaa caatgggagt 240gacgtgctaa aacctggaaa cctaaaacaa tgcgagtgag gtgctaacac cagaatccat 300aacaatgtga gtgacgtgct aaaccagaac ccaaaacaat gggagtgacg tgctaaaaca 360ggaacccaaa acaatgagag tgacgtgcta aaccagaaac ccaaaacaat gggaatgacg 420tgctaaaacc ggaacccaaa acaatgggag tgatgtgcta aaccagaaac ccaaaacaat 480gggaatgaca tgctaaaact ggaacccaaa acaatggtaa ctaagagtga tgctaaggcc 540ctacattttg gtcacactct caactaagtg agaacttgac tgaaaaggag gatttttttt 600tctaagacag agttttggtc tgtcccccag agtggagtgc agtggcatga tctcggctca 660ctgcaagctc tgcctcccgg gttcaggcca ttctcctgcc tcagcctcct gagtagctgg 720gaatacaggc acccgccacc acacttggct aattttttgt atttttagta gagatggggt 780ttcaccatat tagcaaggat ggtctcaatc tcctgacctc gtgatctgcc cacctcaggc 840tcccaaagtg ctgggattac aggtgtgagc caccacaccc agcaaaaagg aggaattttt 900aaagcaaaat tatgggaggc cattgttttg aactaagctc atgcaatagg tcccaacaga 960ccaaaccaaa ccaaaccaaa atggagtcac tcatgctaaa tgtagcataa tcaaa 1015502355DNAArtificial Sequencesequence of STAR50 50caaccatcgt tccgcaagag cggcttgttt attaaacatg aaatgaggga aaagcctagt 60agctccattg gattgggaag aatggcaaag agagacaggc gtcattttct agaaagcaat 120cttcacacct gttggtcctc acccattgaa tgtcctcacc caatctccaa cacagaaatg 180agtgactgtg tgtgcacatg cgtgtgcatg tgtgaaagta tgagtgtgaa tgtgtctata 240tgggaacata tatgtgattg tatgtgtgta actatgtgtg actggcagcg tggggagtgc 300tggttggagt gtggtgtgat gtgagtatgc atgagtggct gtgtgtatga ctgtggcggg 360aggcggaagg ggagaagcag caggctcagg tgtcgccaga gaggctggga ggaaactata 420aacctgggca atttcctcct catcagcgag cctttcttgg gcaatagggg cagagctcaa 480agttcacaga gatagtgcct gggaggcatg aggcaaggcg gaagtactgc gaggaggggc 540agagggtctg acacttgagg ggttctaatg ggaaaggaaa gacccacact gaattccact 600tagccccaga ccctgggccc agcggtgccg gcttccaacc ataccaacca tttccaagtg 660ttgccggcag aagttaacct ctcttagcct cagtttcccc acctgtaaaa tggcagaagt 720aaccaagctt accttcccgg cagtgtgtga ggatgaaaag agctatgtac gtgatgcact 780tagaagaagg tctagggtgt gagtggtact cgtctggtgg gtgtggagaa gacattctag 840gcaatgagga ctggggagag cctggcccat ggcttccact cagcaaggtc agtctcttgt 900cctctgcact cccagccttc cagagaggac cttcccaacc agcactcccc acgctgccag 960tcacacatag ttacacacat acaatcacat atatgttccc atatagacac attcacactc 1020ataccttcac acatgcacac gcatgtgcac acacagtcac tcatttctgt gttggagatt 1080gggtgaggac attcaatggg tgaggaccaa caggtgtgaa gattgctttc tagaaaatga 1140ctcctgtctc tctttgccat tcttcccaat ccgatggagc tactaggctt ttccctcatt 1200tcatgtttaa taaaccttcc caatggcgaa atgggctttc tcaagaagtg gtgagtgtcc 1260catccctgcg gtggggacag gggtggcagc ggacaagcct gcctggaggg aactgtcagg 1320ctgattccca gtccaactcc agcttccaac acctcatcct ccaggcagtc ttcattcttg 1380gctctaattt cgctcttgtt ttctttttta tttttatcga gaactgggtg gagagctttt 1440ggtgtcattg gggattgctt tgaaaccctt ctctgcctca cactgggagc tggcttgagt 1500caactggtct ccatggaatt tcttttttta gtgtgtaaac agctaagttt taggcagctg 1560ttgtgccgtc cagggtggaa agcagcctgt tgatgtggaa ctgcttggct cagatttctt 1620gggcaaacag atgccgtgtc tctcaactca ccaattaaga agcccagaaa atgtggcttg 1680gagaccacat gtctggttat gtctagtaat tcagatggct tcacctggga agccctttct 1740gaatgtcaaa gccatgagat aaaggacata tatatagtag ctagggtggt ccacttctta 1800ggggccatct ccggaggtgg tgagcactaa gtgccaggaa gagaggaaac tctgttttgg 1860agccaaagca taaaaaaacc ttagccacaa accactgaac atttgttttg tgcaggttct 1920gagtccaggg agggcttctg aggagagggg cagctggagc tggtaggagt tatgtgagat 1980ggagcaaggg ccctttaaga ggtgggagca gcatgagcaa aggcagagag gtggtaatgt 2040ataaggtatg tcatgggaaa gagtttggct ggaacagagt ttacagaata gaaaaattca 2100acactattaa ttgagcctct actacgtgct cgacattgtt ctagtcactg agataggttt 2160ggtatacaaa acaaaatcca tcctctatgg acattttagt gactaacaac aatataaata 2220ataaaagtga acaaaagctc aaaacatgcc aggcactatt atttatttat ttatttattt 2280atttatttat tttttgaaac agagtctcgc tctgttgccc aggctggagt gtagtggtgc 2340gatctcggct cactg 2355512289DNAArtificial Sequencesequence of STAR51 51tcacaggtga caccaatccc ctgaccacgc tttgagaagc actgtactag attgactttc 60taatgtcagt cttcattttc tagctctgtt acagccatgg tctccatatt atctagtaca 120acacacatac aaatatgtgt gatacagtat gaatataata taaaaatatg tgttataata 180taaatataat attaaaatat gtctttatac tagataataa tacttaataa cgttgagtgt 240ttaactgctc taagcacttt acctgcagga aacagttttt tttttatttt ggtgaaatac 300aactaacata aatttattta caattttaag catttttaag tgtatagttt agtggagtta 360atatattcaa aatgttgtgc agccgtcacc atcatcagtc ttcataactc ttttcatatt 420gtaaaattaa aagtttatgc tcatttaaaa atgactccca atttcccccc tcctcaacct 480ctggaaacta ccattctatt ttctgcctcc gtagttttgc ccactctaag tacctcacat 540aagtggaatt tgtcttattt gcctgtttgt gaccggctga tttcatttag tataatgtcc 600tcaagtttta ttcacgttat atagcatatg tcataatttt cttcactttt aagcttgagt 660aatatttcat cgtatgtatc tcacattttg cttatccatt catctctcag tggacacttg 720agttgcttct acattttagc tgttgtgaat actgctgcta tgaacatggg tgtataaata 780tctcaagacc tttttatcag ttttttaaaa tatatactca gtagtagttt agctggatta 840tatggtaatt ttatttttaa tttttgagga actgtcctac ccttttattc aatagtagct 900ataccaattg acaattggca ttcctaccaa cagggcataa gggttctcaa ttctccacat 960attccctgat acttgttatt ttcaggtgtt tttttttttt tttttttttt atgggagcca 1020tgttaatggg tgtaaggtga tatttcatta tagttttgat ttgcatttcc ctaatgatta 1080gtgatgttaa gcatctcttc atgtgcctat tggccatttg tatatcttct ttaaaaatat 1140atatatactc attcctttgc ccatttttga attatgttta ttttttgtta ttgagtttca 1200atacttttct atataaccta ggtattaatc ctttatcaga cttaagattt gcaaatattc 1260tctttcattc cacaggttgc taattctctc tgttggtaat atcttttgat gctgttgtgt 1320ccagaattga ttcattcctg tgggttcttg gtctcactga cttcaagaat aaagctgcgg 1380accctagtgg tgagtgttac acttcttata gatggtgttt ccggagtttg ttccttcaga 1440tgtgtccaga gtttcttcct tccaatgggt tcatggtctt gctgacttca ggaatgaagc 1500cgcagacctt cgcagtgagg tttacagctc ttaaaggtgg cgtgtccaga gttgtttgtt 1560ccccctggtg ggttcgtggt cttgctgact tcaggaatga agccgcagac cctcgcagtg 1620agtgttacag ctcataaagg tagtgcggac acagagtgag ctgcagcaag atttactgtg 1680aagagcaaaa gaacaaagct tccacagcat agaaggacac cccagcgggt tcctgctgct 1740ggctcaggtg gccagttatt attcccttat ttgccctgcc cacatcctgc tgattggtcc 1800attttacaga gtactgattg gtccatttta cagagtgctg attggtgcat ttacaatcct 1860ttagctagac acagagtgct gattgctgca ttcttacaga gtgctgattg gtgcatttac 1920agtcctttag ctagatacag aacgctgatt gctgcgtttt ttacagagtg ctgattggtg 1980catttacaat cctttagcta gacacagtgc tgattggtgg gtttttacag agtgctgatt 2040ggtgcgtctt tacagagtgc tgattggtgc atttacaatc ctttagctag acacagagtg 2100ctgattggtg cgtttataat cctctagcta gacagaaaag ttttccaagt ccccacctga 2160ccgagaagcc ccactggctt cacctctcac tgttatactt tggacatttg tccccccaaa 2220atctcatgtt gaaatgtaac ccctaatgtt ggaactgagg ccagactgga tgtggctggg 2280ccatgggga 2289521184DNAArtificial Sequencesequence of STAR52 52cttatgccat ctggcggtgc catgtggaac ttcgctgaag aagctaaatt tactgaccat 60ctgtgcctag agcgggtttc tccaaggaaa ggctctgtaa atctcgtcct tttgaaatct 120aggggaaaac agcctccttc actgaggatt aatttaaaga aagggggaaa taggaaaatt 180ccatgcgttg gaagtccatt tagatttcta catgaaccat catatatgtg cactacataa 240ttcttatttt tttattttta aaaaagggat aatttatatt ccagtgacaa gtttgggaaa 300ggccaaggca agcaattgag ttgaacatta tgtagcgttt atatagacct tgcagacgtc 360tgtgcaatat ccaccactga acacgtgagg tcgtactcaa gtctctctgg cccctggtaa 420tgtgactccc ttcctttatt tgcatgaatc gcctggattg ggtgtcaggt ttttaaaacg 480tcaaggttta cgcctattgt tgtcaaccaa tcagcatcct actttgacgt gattggcttc 540tactgtaggt gtcaatcatc caaaatttgc atactactcc tcaggccgcc gggagcctgt 600cagtcggctg tggcagctgg aagagaagga atcggacgga gaagaatgaa aaatcacttt 660gctttcgcaa agcgaaagaa aagtattctt ttcctcatta tttttaaata aatttgattg 720tatatttacc taataaaata aacattcaat taaacaaaaa taagcaacta tcaaagattt 780gtttactaat tttcgtaatg tttactgttt caataagtag ccaaaggaat attaaaacac 840aaaaatatga atgctgataa ttttatgtca taaagaccat tttaaaacta aaagtgaaca 900tggggtttct aaataaaatt accgtggtag cgtaaaaaca ctgctttcaa tacttgggca 960tgctgaaagt gctgcatcct aagataaaaa atacaccaag ggggggattt caaagaacat 1020tattttgctt ttaataatcc tgtatttctg tcactttgcc ctttttattt atttaccgtg 1080aactcacaga cagaatatta cttggagttt ctgaaatact tgtgtttgta catttctcat 1140cttacacgta cccacacacc ccaaaataaa aaaacaaaga agag 1184531431DNAArtificial Sequencesequence of STAR53 53ccctgaggaa gatgacgagt aactccgtaa gagaaccttc cactcatccc ccacatccct 60gcagacgtgc tattctgtta tgatactggt atcccatctg tcacttgctc cccaaatcat 120tcccttctta caattttcta ctgtacagca ttgaggctga acgatgagag atttcccatg 180ctctttctac tccctgccct gtatatatcc ggggatcctc cctacccagg atgctgtggg 240gtcccaaacc ccaagtaagc cctgatatgc gggccacacc tttctctagc ctaggaattg 300ataacccagg cgaggaagtc actgtggcat gaacagatgg ttcacttcga ggaaccgtgg 360aaggcgtgtg caggtcctga gatagggcag aatcggagtg tgcagggtct gcaggtcagg 420aggagttgag attgcgttgc cacgtggtgg gaactcactg ccacttattt ccttctctct 480tcttgcctca gcctcaggga tacgacacat gcccatgatg agaagcagaa cgtggtgacc 540tttcacgaac atgggcatgg ctgcggaccc ctcgtcatca ggtgcatagc aagtgaaagc 600aagtgttcac aacagtgaaa agttgagcgt catttttctt agtgtgccaa gagttcgatg 660ttagcgttta cgttgtattt tcttacactg tgtcattctg ttagatacta acattttcat 720tgatgagcaa gacatactta atgcatattt tggtttgtgt atccatgcac ctaccttaga 780aaacaagtat tgtcggttac ctctgcatgg aacagcatta ccctcctctc tccccagatg 840tgactactga gggcagttct gagtgtttaa tttcagattt tttcctctgc atttacacac 900acacgcacac

aaaccacacc acacacacac acacacacac acacacacac acacacacac 960acacaccaag taccagtata agcatctgcc atctgctttt cccattgcca tgcgtcctgg 1020tcaagctccc ctcactctgt ttcctggtca gcatgtactc ccctcatccg attcccctgt 1080agcagtcact gacagttaat aaacctttgc aaacgttccc cagttgtttg ctcgtgccat 1140tattgtgcac acagctctgt gcacgtgtgt gcatatttct ttaggaaaga ttcttagaag 1200tggaattgct gtgtcaaagg agtcatttat tcaacaaaac actaatgagt gcgtcctcgt 1260gctgagcgct gttctaggtg ctggagcgac gtcagggaac aaggcagaca ggagttcctg 1320acccccgttc tagaggagga tgtttccagt tgttgggttt tgtttgtttg tttcttctag 1380agatggtggt cttgctctgt ccaggctaga gtgcagtggc atgatcatag c 143154975DNAArtificial Sequencesequence of STAR54 54ccataaaagt gtttctaaac tgcagaaaaa tccccctaca gtcttacagt tcaagaattt 60tcagcatgaa atgcctggta gattacctga ctttttttgc caaaaataag gcacagcagc 120tctctcctga ctctgacttt ctatagtcct tactgaatta tagtccttac tgaattcatt 180cttcagtgtt gcagtctgaa ggacacccac attttctctt tgtctttgtc aattctttgt 240gttgtaaggg caggatgttt aaaagttgaa gtcattgact tgcaaaatga gaaatttcag 300agggcatttt gttctctaga ccatgtagct tagagcagtg ttcacactga ggttgctgct 360aatgtttctg cagttcttac caatagtatc atttacccag caacaggata tgatagagga 420cttcgaaaac cccagaaaat gttttgccat atatccaaag ccctttggga aatggaaagg 480aattgcgggc tcccattttt atatatggat agatagagac caagaaagac caaggcaact 540ccatgtgctt tacattaata aagtacaaaa tgttaacatg taggaagtct aggcgaagtt 600tatgtgagaa ttctttacac taattttgca acattttaat gcaagtctga aattatgtca 660aaataagtaa aaatttttac aagttaagca gagaataaca atgattagtc agagaaataa 720gtagcaaaat cttcttctca gtattgactt ggttgctttt caatctctga ggacacagca 780gtcttcgctt ccaaatccac aagtcacatc agtgaggaga ctcagctgag actttggcta 840atgttggggg gtccctcctg tgtctcccca ggcgcagtga gcctgcaggc cgacctcact 900cgtggcacac aactaaatct ggggagaagc aacccgatgc cagcatgatg cagatatctc 960agggtatgat cggcc 97555501DNAArtificial Sequencesequence of STAR55 55cctgaactca tgatccgccc acctcagcct cctgaagtgc tgggattaca ggtgtgagcc 60accacaccca gccgcaacac actcttgagc aaccaatgtg tcataaaaga aataaaatgg 120aaatcagaaa gtatcttgag acagacaaaa atggaaacac aacataccaa aatttatggg 180acacagcaaa agcagtttta ggagggaagt ttatagtgat gaatacctac ctcaaaatca 240ttagcctgat tggatgacac tacagtgtat aaatgaattg aaaaccacat tgtgccccat 300acatatatac aatttttatt tgttaattaa aaataaaata aaactttaaa aaagaagaaa 360gagctcaaat aaacaaccta actttatacc tcaaggaaat agaagagcca gctaagccca 420aagttgacag aaggaaaaaa atattggcag aaagaaatga aacagagact agaaagacaa 480ttgaagagat cagcaaaact a 50156741DNAArtificial Sequencesequence of STAR56 56acacaggaaa agatcgcaat tgttcagcag agctttgaac cggggatgac ggtctccctc 60gttgcccggc aacatggtgt agcagccagc cagttatttc tctggcgtaa gcaataccag 120gaaggaagtc ttactgctgt cgccgccgga gaacaggttg ttcctgcctc tgaacttgct 180gccgccatga agcagattaa agaactccag cgcctgctcg gcaagaaaac gatggaaaat 240gaactcctca aagaagccgt tgaatatgga cgggcaaaaa agtggatagc gcacgcgccc 300ttattgcccg gggatgggga gtaagcttag tcagccgttg tctccgggtg tcgcgtgcgc 360agttgcacgt cattctcaga cgaaccgatg actggatgga tggccgccgc agtcgtcaca 420ctgatgatac ggatgtgctt ctccgtatac accatgttat cggagagctg ccaacgtatg 480gttatcgtcg ggtatgggcg ctgcttcgca gacaggcaga acttgatggt atgcctgcga 540tcaatgccaa acgtgtttac cggatcatgc gccagaatgc gctgttgctt gagcgaaaac 600ctgctgtacc gccatcgaaa cgggcacata caggcagagt ggccgtgaaa gaaagcaatc 660agcgatggtg ctctgacggg ttcgagttct gctgtgataa cggagagaga ctgcgtgtca 720cgttcgcgct ggactgctgt g 741571365DNAArtificial Sequencesequence of STAR57 57tccttctgta aataggcaaa atgtatttta gtttccacca cacatgttct tttctgtagg 60gcttgtatgt tggaaatttt atccaattat tcaattaaca ctataccaac aatctgctaa 120ttctggagat gtggcagtga ataaaaaagt tatagtttct gattttgtgg agcttggact 180ttaatgatgg acaaaacaac acattcttaa atatatattt catcaaaatt atagtgggtg 240aattatttat atgtgcattt acatgtgtat gtatacataa atgggcggtt actggctgca 300ctgagaatgt acacgtggcg cgaacgaggc tgggcggtca gagaaggcct cccaaggagg 360tggctttgaa gctgagtggt gcttccacgt gaaaaggctg gaaagggcat tccaagaaaa 420ggctgaggcc agcgggaaag aggttccagt gcgctctggg aacggaaagc gcacctgcct 480gaaacgaaaa tgagtgtgct gaaataggac gctagaaagg gaggcagagg ctggcaaaag 540cgaccgagga ggagctcaaa ggagcgagcg gggaaggccg ctgtggagcc tggaggaagc 600acttcggaag cgcttctgag cgggtaaggc cgctgggagc atgaactgct gagcaggtgt 660gtccagaatt cgtgggttct tggtctcact gacttcaaga atgaagaggg accgcggacc 720ctcgcggtga gtgttacagc tcttaaggtg gcgcgtctgg agtttgttcc ttctgatgtt 780cggatgtgtt cagagtttct tccttctggt gggttcgtgg tctcgctggc tcaggagtga 840agctgcagac cttcgcggtg agtgttacag ctcataaaag cagggtggac tcaaagagtg 900agcagcagca agatttattg caaagaatga aagaacaaag cttccacact gtggaagggg 960accccagcgg gttgccactg ctggctccgc agcctgcttt tattctctta tctggcccca 1020cccacatcct gctgattggt agagccgaat ggtctgtttt gacggcgctg attggtgcgt 1080ttacaatccc tgcgctagat acaaaggttc tccacgtccc caccagatta gctagataga 1140gtctccacac aaaggttctc caaggcccca ccagagtagc tagatacaga gtgttgattg 1200gtgcattcac aaaccctgag ctagacacag ggtgatgact ggtgtgttta caaaccttgc 1260ggtagataca gagtatcaat tggcgtattt acaatcactg agctaggcat aaaggttctc 1320caggtcccca ccagactcag gagcccagct ggcttcaccc agtgg 1365581401DNAArtificial Sequencesequence of STAR58 58aagtttacct tagccctaaa ttatttcatt gtgattggca ttttaggaaa tatgtattaa 60ggaatgtctc ttaggagata aggataacat atgtctaaga aaattatatt gaaatattat 120tacatgaact aaaatgttag aactgaaaaa aaattattgt aactccttcc agcgtaggca 180ggagtatcta gataccaact ttaacaactc aactttaaca acttcgaacc aaccagatgg 240ctaggagatt cacctattta gcatgatatc ttttattgat aaaaaaatat aaaacttcca 300ttaaattttt aagctactac aatcctatta aattttaact taccagtgtt ctcaatgcta 360cataatttaa aatcattgaa atcttctgat tttaactcct cagtcttgaa atctacttat 420ttttagttac atatatatcc aatctactgc cgctagtaga agaagcttgg aatttgagaa 480aaaaatcaga cgttttgtat attctcatat tcactaattt attttttaaa tgagtttctg 540caatgcatca agcagtggca aaacaggaga aaaattaaaa ttggttgaaa agatatgtgt 600gccaaacaat cccttgaaat ttgatgaagt gactaatcct gagttattgt ttcaaatgtg 660tacctgttta tacaagggta tcacctttga aatctcaaca ttaaatgaaa ttttataagc 720aatttgttgt aacatgatta ttataaaatt ctgatataac attttttatt acctgtttag 780agtttaaaga gagaaaagga gttaagaata attacatttt cattagcatt gtccgggtgc 840aaaaacttct aacactatct tcaaatcttt ttctccattg ccttctgaac atacccactt 900gggtatctca ttagcactgc aaattcaaca ttttcgattg ctaatttttc tccctaaata 960tttatttgtt ttctcagctt tagccaatgt ttcactattg accatttgct caagtatagt 1020gacgcttcaa tgaccttcag agagctgttt cagtccttcc tggactactt gcatgcttcc 1080aacaaaatga agcactcttg atgtcagtca ctcaaataaa tggaaatggg cccatttact 1140aggaatgtta acagaataaa aagatagacg tgacaccagt tgcttcagtc catctccatt 1200tacttgctta aggcctggcc atatttctca cagttgatat ggcgcagggc acatgtttaa 1260atggctgttc ttgtaggatg gtttgactgt tggattcctc atcttccctc tccttaggaa 1320ggaaggttac agtagtactg ttggctcctg gaatatagat tcataaagaa ctaatggagt 1380atcatctccc actgctcttg t 140159866DNAArtificial Sequencesequence of STAR59 59gagatcacgc cactgcactc cagcctgggg gacagagcaa gactccatct cagaaacaaa 60caaacacaca aagccagtca aggtgtttaa ttcgacggtg tcaggctcag gtctcttgac 120aggatacatc cagcacccgg gggaaacgtc gatgggtggg gtggaatcta ttttgtggcc 180tcaagggagg gtttgagagg tagtcccgca agcggtgatg gcctaaggaa gcccctccgc 240ccaagaagcg atattcattt ctagcctgta gccacccaag agggagaatc gggctcgcca 300cagaccccac aacccccaac ccaccccacc cccacccctc ccacctcgtg aaatgggctc 360tcgctccgtc aggctctagt cacaccgtgt ggttttggaa cctccagcgt gtgtgcgtgg 420gttgcgtggt ggggtggggc cggctgtgga cagaggaggg gataaagcgg cggtgtcccg 480cgggtgcccg ggacgtgggg cgtggggcgt gggtggggtg gccagagcct tgggaactcg 540tcgcctgtcg ggacgtctcc cctcctggtc ccctctctga cctacgctcc acatcttcgc 600cgttcagtgg ggaccttgtg ggtggaagtc accatccctt tggactttag ccgacgaagg 660ccgggctccc aagagtctcc ccggaggcgg ggccttgggc aggctcacaa ggatgctgac 720ggtgacggtt ggtgacggtg atgtacttcg gaggcctcgg gccaatgcag aggtatccat 780ttgacctcgg tgggacaggt cagctttgcg gagtcccgtg cgtccttcca gagactcatc 840cagcgctagc aagcatggtc ccgagg 866602067DNAArtificial Sequencesequence of STAR60 60agcagtgcag aactggggaa gaagaagagt ccctacacca cttaatactc aaaagtactc 60gcaaaaaata acacccctca ccaggtggca tnattactct ccttcattga gaaaattagg 120aaactggact tcgtagaagc taattgcttt atccagagcc acctgcatac aaacctgcag 180cgccacctgc atacaaacct gtcagccgac cccaaagccc tcagtcgcac caagcctctg 240ctgcacaccc tcgtgccttc acactggccg ttccccaagc ctggggcata ctncccagct 300ctgagaaatg tattcatcct tcaaagccct gctcatgtgt cctnntcaac aggaaaatct 360cccatgagat gctctgctat ccccatctct cctgccccat agcttaggca nacttctgtg 420gtggtgagtc ctgggctgtg ctgtgatgtg ttcgcctgcn atgtntgttc ttccccacaa 480tgatgggccc ctgaattctc tatctctagc acctgtgctc agtaaaggct tgggaaacca 540ggctcaaagc ctggcccaga tgccaccttt tccagggtgc ttccgggggc caccaaccag 600agtgcagcct tctcctccac caggaactct tgcagcccca cccctgagca cctgcacccc 660attacccatc tttgtttctc cgtgtgatcg tattattaca gaattatata ctgtattctt 720aatacagtat ataattgtat aattattctt aatacagtat ataattatac aaatacaaaa 780tatgtgttaa tggaccgttt atgttactgg taaagcttta agtcaacagt gggacattag 840ttaggttttt ggcgaagtca aaagttatat gtgcattttc aacttcttga ggggtcggta 900cntctnaccc ccatgttgtt caanggtcaa ctgtctacac atatcatagc taattcacta 960cagaaatgtt agcttgtgtc actagtatct ccccttctca taagcttaat acacatacct 1020tgagagagct cttggccatc tctactaatg actgaagttt ttatttatta tagatgtcat 1080aataggcata aaactacatt acatcattcg agtgccaatt ttgccacctt gaccctcttt 1140tgcaaaacac caacgtcagt acacatatga agaggaaact gcccgagaac tgaagttcct 1200gagaccagga gctgcaggcg ttagatagaa tatggtgacg agagttacga ggatgacgag 1260agtaaatact tcatactcag tacgtgccaa gcactgctat aagcgctctg tatgtgtgaa 1320gtcatttaat cctcacagca tcccacggtg taattatttt cattatcccc atgagggaac 1380agaaactcag aacggttcaa cacatatgcg agaagtcgca gccggtcagt gagagagcag 1440gttcccgtcc aagcagtcag accccgagtg cacactctcg acccctgtcc agcagactca 1500ctcgtcataa ggcggggagt gntctgtttc agccagatgc tttatgcatc tcagagtacc 1560caaaccatga aagaatgagg cagtattcan gagcagatgg ngctgggcag taaggctggg 1620cttcagaata gctggaaagc tcaagtnatg ggacctgcaa gaaaaatcca ttgtttngat 1680aaatagccaa agtccctagg ctgtaagggg aaggtgtgcc aggtgcaagt ggagctctaa 1740tgtaaaatcg cacctgagtc tcctggtctt atgagtnctg ggtgtacccc agtgaaaggt 1800cctgctgcca ccaagtgggc catggttcag ctgtgtaagt gctgagcggc agccggaccg 1860cttcctctaa cttcacctcc aaaggcacag tgcacctggt tcctccagca ctcagctgcg 1920aggcccctag ccagggtccc ggcccccggc ccccggcagc tgctccagct tccttcccca 1980cagcattcag gatggtctgc gttcatgtag acctttgttt tcagtctgtg ctccgaggtc 2040actggcagca ctagccccgg ctcctgt 2067611470DNAArtificial Sequencesequence of STAR61 61cagcccccac atgcccagcc ctgtgctcag ctctgcagcg gggcatggtg ggcagagaca 60cagaggccaa ggccctgctt cggggacggt gggcctggga tgagcatggc cttggccttc 120gccgagagtn ctcttgtgaa ggaggggtca ggaggggctg ctgcagctgg ggaggagggc 180gatggcactg tggcangaag tgaantagtg tgggtgcctn gcaccccagg cacggccagc 240ctggggtatg gacccggggc cntctgttct agagcaggaa ggtatggtga ggacctcaaa 300aggacagcca ctggagagct ccaggcagag gnacttgaga ggccctgggg ccatcctgtc 360tcttttctgg gtctgtgtgc tctgggcctg ggcccttcct ctgctccccc gggcttggag 420agggctggcc ttgcctcgtg caaaggacca ctctagactg gtaccaagtc tggcccatgg 480cctcctgtgg gtgcaggcct gtgcgggtga cctgagagcc agggctggca ggtcagagtc 540aggagaggga tggcagtgga tgccctgtgc aggatctgcc taatcatggt gaggctggag 600gaatccaaag tgggcatgca ctctgcactc atttctttat tcatgtgtgc ccatcccaac 660aagcagggag cctggccagg agggcccctg ggagaaggca ctgatgggct gtgttccatt 720taggaaggat ggacggttgt gagacgggta agtcagaacg ggctgcccac ctcggccgag 780agggccccgt ggtgggttgg caccatctgg gcctggagag ctgctcagga ggctctctag 840ggctgggtga ccaggnctgg ggtacagtag ccatgggagc aggtgcttac ctggggctgt 900ccctgagcag gggctgcatt gggtgctctg tgagcacaca cttctctatt cacctgagtc 960ccnctgagtg atgagnacac ccttgttttg cagatgaatc tgagcatgga gatgttaagt 1020ggcttgcctg agccacacag cagatggatg gtgtagctgg gacctgaggg caggcagtcc 1080cagcccgagg acttcccaag gttgtggcaa actctgacag catgacccca gggaacaccc 1140atctcagctc tggtcagaca ctgcggagtt gtgttgtaac ccacacagct ggagacagcc 1200accctagccc cacccttatc ctctcccaaa ggaacctgcc ctttcccttc attttcctct 1260tactgcattg agggaccaca cagtgtggca gaaggaacat gggttcagga cccagatgga 1320cttgcttcac agtgcagccc tcctgtcctc ttgcagagtg cgtcttccac tgtgaagttg 1380ggacagtcac accaactcaa tactgctggg cccgtcacac ggtgggcagg caacggatgg 1440cagtcactgg ctgtgggtct gcagaggtgg 1470621011DNAArtificial Sequencesequence of STAR62 62agtgtcaaat agatctacac aaaacaagat aatgtctgcc catttttcca aagataatgt 60ggtgaagtgg gtagagagaa atgcatccat tctccccacc caacctctgc taaattgtcc 120atgtcacagt actgagacca gggggcttat tcccagcggg cagaatgtgc accaagcacc 180tcttgtctca atttgcagtc taggccctgc tatttgatgg tgtgaaggct tgcacctggc 240atggaaggtc cgttttgtac ttcttgcttt agcagttcaa agagcaggga gagctgcgag 300ggcctctgca gcttcagatg gatgtggtca gcttgttgga ggcgccttct gtggtccatt 360atctccagcc cccctgcggt gttgctgttt gcttggcttg tctggctctc catgccttgt 420tggctccaaa atgtcatcat gctgcacccc aggaagaatg tgcaggccca tctcttttat 480gtgctttggg ctattttgat tccccgttgg gtatattccc taggtaagac ccagaagaca 540caggaggtag ttgctttggg agagtttgga cctatgggta tgaggtaata gacacagtat 600cttctctttc atttggtgag actgttagct ctggccgcgg actgaattcc acacagctca 660cttgggaaaa ctttattcca aaacatagtc acattgaaca ttgtggagaa tgagggacag 720agaagaggcc ctagatttgt acatctgggt gttatgtcta taaatagaat gctttggtgg 780tcaactagac ttgttcatgt tgacatttag tcttgccttt tcggtggtga tttaaaaatt 840atgtatatct tgtttggaat atagtggagc tatggtgtgg cattttcatc tggctttttg 900tttagctcag cccgtcctgt tatgggcagc cttgaagctc agtagctaat gaagaggtat 960cctcactccc tccagagagc ggtcccctca cggctcattg agagtttgtc a 1011631410DNAArtificial Sequencesequence of STAR63 63gcgtctgagc cgctgggaac ccatgagccc cgtccatgga gttgaggaag ggggttcgcc 60ccacggggtg ggcgccctct acacagcgcg cttcctcttc tctcgttagc gccgcgggac 120cagcctctgg ttctgcacct cgcgctctgg gagcagcgcc cggctttggc gagcgcttcc 180ccggggctgc ccagcctctg ctccgctcgc cccgccaggc ccggctccgc gaagccccca 240gggtccagtc caaggccccg attccccaag gccagggccc cggggcagca ttggaacagg 300gcgcggacgc cagtcctccg agcatggagt aactgcagct tttgagaaaa gaaagcggac 360cccaccccat cgagaacgcg gcgccttgtt tagggacgtt cctgggccgt cacggagtgt 420cgccggctcc tcggcccctc cctcctccaa gcccccaccc ccgacagcgg cctccctggg 480gacctcccct cgggctgcgc tttcagccca aacacaggga ggtcttccag gagcctgccc 540agtccccaca gcagcccaga gacccccact cccacctgta cctgccaagc cttcagagag 600ggcggcctgg acatgccccg cacgggagga gccccgcctc agcacccctg caagtggcag 660caacccagaa cacccgtgag aggcctctga gcagcccagg aagtggctgg aagacgcata 720ggcagctcac tcctctgtaa gagcaaggac cggagaacac atgctgaccc ctgcttttgc 780agaggggcga tgcttcagga caggcgcgct cagcaggtgt ccatcttatt tcacaccttt 840gtgtttatat catcttattt tgcattttat gtctaattaa caatatgcag ctggccaggc 900gcagtggctc aagcctctaa tcccagcact ttgggaggcc gaggcaggtg tatcacttga 960gggcaggagt tcgggaccgg cctgggcaac atagcaaaac cccattgcta ataaaaatac 1020aaaaattagc cagccatggt ggcgggcacc tgcagtccca gctactccgg aagctgaagc 1080aggagaatca cttgaaccca ggaggcggag gtggcagtga gctatcaagc cattacactc 1140cagcctgggc aacagagaaa gactgtctca aaaaaaaatt aatacgcagc agaatattat 1200gtggtcagcc caagcagtcc cccccactca gccctctgtc cctacagctc caggcactcc 1260cccagcccct cccctggaca agaggtaatg cccagagggt gaaaatccac caaggttaag 1320ccagaaacaa aaagctcaaa gcttcggcat ctccctccgc tcagaccctt agagcagatt 1380cctctcatcg acagcacgat caggctgtgg 1410641414DNAArtificial Sequencesequence of STAR64 64agagatcttt taagggctca aaagaccctg cggctcccct gccaatagct ctgccatcgt 60ccccagagct ttcgaggacc ctccaccatc ggcgccaacc ccagctgagc tgggtgctcg 120tctgcaggcc tctgctccat ctcagcctga gcatgaggct ctgctgtgct gcttccagca 180gcagggacag ggctgatgag cctggccctt gcaagcatct tcctgtgccg aatacaattc 240cacagacaga ggatttaaaa tccaagtgga ggtgacagga aagaaaggaa aacctccagg 300tatcagaaga aaggaggggg tgtgaagaca gtatgggagg aaggtcaggc tggggctcag 360ctctgggaag tgccagcctg aacaggagtc acgcccgggt ccacatgcaa gggaatgagg 420accgaggccc tgcatgtggc agggccttcc gcaggctgcc ccgtctgtga acaggacacc 480agaagaagtc tgccttccag cctggcaaag tggcaaggaa cctctgggtg ggaaaacaaa 540tcaacaaaca aattgtcagt aaaaaacaga aacctcacac tttcctttct cttgacctct 600tgaaaaaagc aaatccactg cagctcacca aaggcaaaga gaaaacctta agaataccca 660gagagaaaag acacgttact tgcaaaagaa catctaatgc agggagataa tgaaaataca 720gactcttcaa agggctgaag gaaaaaaacc gtccacctag aattctatcc ccaaactgtc 780atctgagagc aagggcaaaa caaacgcttt ctcagacagg ctggacgagg tcgctcacgc 840ctgtaatcct agcactttgg gaggccaagg tgggaggacc gctttaagcc agaagtttga 900gaccagtgtg ggtaacataa tgagacccca tctctaagaa aaagaaatta aataagacaa 960gactttttca gacaacaagt gctctgagag ctggcctatc ttggctgtct tgtaaagaat 1020tgctgcgaga cacctcatta ggaaagagac tgaatctaga aggaaagagc agagcatgag 1080gtacaatgag gagcaaataa acaggtcacc atataagcaa acccaaatac acattcacta 1140tacgaaacaa taaaaatgac tcatttgggg ggttaaaaca ctgttgaact aaaatcctgg 1200ataacagcag catgaaaggt ggggtggtgg tcccaggaaa gcattcaaag gtccatgtct 1260catttgggag gagggtaggg agactcatga acttgaggct cccttcaggc aagcacagtg 1320caaaaaaatt ataataatgg gaaacagata cagtagactg tgatgtacaa ctctcagagc 1380agtagaaggg agggtataaa acaaatctga tcca 1414651310DNAArtificial Sequencesequence of STAR65 65tcgagaccag cctggccaac atggtgaaac attgtctcta ttacaaatac aaaaattagc 60caggtgtagt ggtgcatgcc tgcagtccca gccatttggg aggctgaagt tggagaatcg 120cttaaacctg ggaggtggag gttgcattga gccgagaagc actccagcct ggatgacgga 180gcaagactgt ctcaaaaaga aaaaaaaaag aagcagcagc aaatatccct gtcctgatgg 240aggctatata acaaccaaac aagtgaatgc ataagacaat ttcaaggtta tggtagatac 300cataagtggg agatgaacaa tgagaacaca tggacacagg gaggagaaca tcacacactg 360gggcctctcg gggggtgggg aaataggggg tgatagcatt aggagaaata cctaatgtcg 420ataacaggtt

agtgggtgca gcaaaccacc atggcacgtg tatatctatg taacacacct 480gcacgttctg cacatgtatc ccagaactta aagtataata aaaaaagaca ttaaaaaatt 540atgatataaa atcccaattc aagttgtttt aaaaagagaa aacaattatc tttatataat 600agcggaaaat atagatggcg gaattaaagc ctcgtcatat tttctaacag aactttctga 660taaacttgat taaataaaaa ttttaaatat cactaaacac atagaagaaa taaatttaaa 720ccttcacaaa aaataaagta caatgaatga agacaaggtg tacttgaaaa aagaactgaa 780taaatattct acatataaaa aaaatctgat gatattgtgg tgattcttta ctttgctact 840agtttctctt tttttcttct gaaaaatttc ttgggatgta tttggtttca ttagtaaaat 900tctaagtttc tttgcaatct gaacattgga gcttcatcca tagccagtat gccctaacat 960tatctttgga caactgtaaa attagaacac tgccagacat atttaatgta tgatgtatat 1020caacactggg acacatttta tactatcttt attccaaaat caaatgattc actgtggttt 1080ataaatgtac atggatatat ctctacctaa gcagatagtt aggagagtta gtaaaaatga 1140ggtggaaaat aggagtcact gtcccttcac agggagagaa ttctgctttt ctcctaatat 1200accctttgct tgaacagact ccaacccctc atcttttgtc ctttaaatga ccacatttat 1260tttaactttg ataaacaaca cagaaagata tttgatccat caacattcac 1310662500DNAArtificial Sequencesequence of T2F (STAR66F) 66gcaggttgga tggtgctgac ccctcctcgg gttggcttcc tgtctccagg tggacgtcct 60gtactccagg gtctgcaagc ctaaaaggag ggacccagga cccaccacag acccgctgga 120ccccaagggc cagggagcga ttctggccct ggcgggtgac ctggcctacc agaccctccc 180gctcagggcc ctggatgtgg acagcggccc cctggaaaac gtgtatgaga gcatccggga 240gctgggggac cctgctggca ggagcagcac gtgcggggct gggacgcccc ctgcttccag 300ctgccccagc ctagggaggg gctggagacc cctccctgcc tccctgccct gaacactcaa 360ggacctgtgc tccttcctcc agagtgaggc ccgtcccccg ccccgccccg cctcacagct 420gacagcgcca gtcccaggtc cccgggctgc cagcccgtga ggtccgtgag gtcctggccg 480ctctgacagc cgcggcctcc ccgggctcca gagaaggccc gcgtctaaat aaagcgccag 540cgcaggatga aagcggccag cctcgcagcc tgctcttctt gaaagctggg cgggttgggg 600cggggggctt ctctggaagg cttggagctg tcccctctgg ccttggggga ctggctgccc 660ccggggcgcc cgggcctagc cgaggcggtg ctcctgccgg ccagactctc ggtcagtgcg 720ggcacggggt cccagccact cctagggggc agcgcagccg gcagggtggc cgcccccggg 780tgggacttgg accctggact ccacgggagg gctccgccac ccagcctggt gttacataag 840gggtggtgga ggtgggcagt cgagcgttaa agagtaacct gctgccggga agcccgccaa 900gcaatcgcgg ccccttcccc ggctctggca gctctgcgag cgcgcccgtg gggaacgggc 960cctccccggc ggggcgcgcg ggcgcgcgag gtgggcggag gcctcggagc tgtgccgggc 1020cgggcctccc tccctaggcc agcgcgggag cgacccggag ggggcgggcc cggggcgggg 1080cctcgaagcg ctggccggcg ggagcgcggc cggccgggcc cgcccgcctg cggtgtggac 1140gccgcgcggc caatgcgcgc gccgggacgg gacgggacgg ggcggggcgg ggcgggacga 1200gacggggcgg ggcggggcgg gccgggcagc ctccgggcgg cgcggcgcgg gcggcggccg 1260gatccagggc gggggtcggc ggcccggcca gcccggcccg gcccggggcc gcgtcctgag 1320agtcagccct cgccgctgca gcctcggcgc ccggccggcc ggccatggag cgccccccgc 1380cccgcgccgc cggccgggac cccagtgcgc tgcgggccga ggcgccgtgg ctgcgcgcgg 1440agggtccggg gccgcgcgcc gcgcccgtga cggtgcccac gccgccgcag gtaccgggcg 1500ccggtgggcg ggggcgccga ccaagtttct ctcgctgcaa agatggcgtc agtgctgccc 1560aaacttcggg cccccggggg cggggcagcg gggagggcgg ccgcgtcggt ccgcgcgtgt 1620ccgtgggtcc cgccggggct gcgccgggcg gccggggagc ccttcccgcc gcgccgggct 1680gggggcgggg ccgggggcgg ggccgcgccg tccacaccgg ccgcagccgg ttttcgaggc 1740gggcgccgag cggatccgcg gcggaggttg agggaccccc ctcccccggc caccgcctcc 1800gctgagtctg ccccctcccc atccgcaggg ctcttccgtg ggcggcggct tcgcgggctt 1860ggagttcgcg cggccgcagg agtcggagcc gcgggcctcg gacctggggg ccccccggac 1920gtggacgggg gcggcggcgg ggccccggac tccgtcggcg cacatccccg tcccagcgca 1980gaggtgagcg ggaggcccgg tgcctcggga ctcggtgtgc gcaggggcgg tgggtggggt 2040gcggagacac cggccccgac ggaggccagg tcagggcccc aggtttgtaa ttaccagcca 2100cccccaagct cttcagccct ggaggagctg agcagaaatg atcgatgact gggagtccct 2160acacctccct ccaccgcagt tcctcggggc tagagctcag aacccggagc gggtggctgt 2220gcgtctctgt gcagaagagg ctgcgcggtc ggcatggggc gactgtccag gaatccctgg 2280ggctcctgac cgccacctcc caacccctgc caggccggac acctcggtct ggctgccagg 2340gcaggggcgg gccctggcct ggctcgctgg ggcctgggga gctgcccgtg cttccagccc 2400agtctccccc tggctgctgc cggctgctgg ccactcccac ctcccaggcc tggcgtgagg 2460cccacagctg ctgttgcaca accctggtta atgtgtgatg 2500672500DNAArtificial Sequencesequence of T2R (STAR66R) 67gtttggggta gagagaacat actgattatg ggactttgct ttgcagctta gtgctgtcct 60gtcagtggga agcaacaggg ggcagaactc agcttgtgcc catagaggga atgtttatac 120taggcctgtc cagaggcaaa tcatccatcc tagcaattgg aacctgactt ttggcaagtc 180ctgccaccat gggctaaagt gttctggggt tctaaataaa catgaaaggc aacctagacc 240acaaggactg caattcctgc acaagtcctg gtgctgtgtt gggcttggag ccagggaact 300tggagtgcat ggaacctagt gagataccag ctgagacaac caaggaagtg cttgtgtcac 360ccctccacca accccaggca gtacagattg tacctccaag accccttcca tctgcttgag 420gaaggtggag gggaagagga ctttgttttg caacttggat tccagcccat ccacagtaga 480ataaggcaac gggcagactc ctaaggcccc catcccagac cctagctcct ggatgacatt 540tctaaacaca ccatgggcca gaagggaacc cattgccttg aagggaaggg cccagtcctg 600gcagaattta tcatgtgctg aataaacagc ccttgggccc tgaataatta gtattggtag 660ccaggcagta tttaccacag gccttgggtg agacccagag ccatgttggc ttcaggtgtg 720acccagcaca ttcccagctg tggtaacttt ggggagagac cacttctgct tgagaaaagg 780agacagaaga gtaaaggggt ctttatcttg cagcctggta ccagcttggc cgcagtgggg 840tagagcacca agagagcacc tgggataaac aaaatcaaaa aacctttagc tagactaaga 900gtaaagagag aagacccaag taaatataat caaagacaaa aaaggagaga cattacaacc 960aatacctcag aaattcaaag tatcattagc agctactttg aacaactata tgccagtaaa 1020ttggaaaacc tagaagaatt atataaattc ctaacatata caacctacca agattgaacc 1080atgaagaaat ttaaagcctg aataggccaa taacaagcaa tgagattgga gccctaatac 1140aaagtttaca atgagaaaca ttgctcaaac aaatcataga tgacacaaac aaatggaaaa 1200catccaatgc tcatggacag gaaaaaatat ttaaatttct atactgccca aagcagttta 1260tacattcaat gctattcctg tcaaaatacc aatcttattc ttcacaaaaa aaaaattaaa 1320aattacacag aaccaaaaaa gagcccaaat acccaaggca attttaagca aaaagaacaa 1380agctggaggc atcacgttac ctgtgatcca cactataggg ctacagtaaa tgaaacagca 1440aggtgctggt atacaaacag acacataaac caatggaata gaataaagag cttagaaata 1500atgctccaca cctccagcca tccgatgttt gagaaagtag acataaacaa gcaatgagga 1560gaggactccc tattcattaa atcaactcaa gacggaccaa aaacctaaat gtaaaacaaa 1620caaacaaaaa aaataactgc taaaaccctg ggagatgacc taggaaatac cattctggac 1680agtacctggt gaaaatttca tgctgaagac accaaaaaca attgcagcaa aagaaaaaat 1740tgacatatgg gatcaaatta aactttagag cttttgcaca gcaaaataaa ctatcaacag 1800agtaaatagg caccctacag gaagggagaa aatattttca atctgtgctc tgacaaagtc 1860ctaatatcca gagcctataa ggaacttaaa caaatttaca aacaaaaaac aaacaacact 1920attacgagtt ggaaaaggac atgaatcgac acttttcaaa agaagacata catgtggcta 1980acaagcatat gaaaaaaatg ctcaacatta ctaatcatta gagaaatgca aatcaaaacc 2040acaatgagat accatctcaa ccagtctgaa tggctgttat taaaaaaatc agaaaaaaac 2100agatgctggc aaggttgtgg agaaaaggaa acacttatac attgttgggg ggagtgtaaa 2160ttaattcagc cattgtggaa agtattgtgg tgattttcta aagaactaaa aaggaattac 2220tattttacct ggaaatttca ttattgggta tatacccaaa gaaatatgaa ttattttact 2280ataaagacag atgcatgcat gtgttcattg tagcactatt cacagtagca aagacatgtt 2340atcaacctaa atgcccatta acagtaaact ggataaggaa aatatggtac atatacactg 2400tggaatacta tgcagtcata aaaagaatga gataatgttc attgcagcaa catggatgga 2460actggagacc attatccttg ggaaactaac aaagcaacag 2500682501DNAArtificial Sequencesequence of T3F 68agatttgccc tcaagattac aactgctggg gctaaagtgg tacagagcct gagttcagta 60ggcttccata gtctcactca agaatgcaag tttacctctc aatctttcaa tcatcacaat 120tataacaact ttaaaaagag ccaacatgat atttgcttat cacttttcta ctcacattcc 180agtattaact caaaagtgtc aacacaacct tcgtgataaa tactattaac gtcatcattc 240ctactgtaca gatgatgata gtgacacata ggttaagttg cccaaggtct tattattaag 300ggtcatagcc aggatttgat ctcttcagta aagttctagt caatgctctt aaccattaag 360ccatgcaaca cacccagagc caactgggtt gtgttgatga ttataatatt tgttttaaca 420aacaataatt tttcctaaat ataatataga ttttccataa ataccataaa ttcttgatta 480tttatttcac tttattccaa aaggaagttg aattctgaga tttaaatgaa tagcaaacaa 540cagttgctta atttcactac ttttgtcact tgtagccagt acttaaaaag agatacataa 600tttatttttg ttgatttgca tttcacatat aattgtaaga tcctggagaa taaagactat 660atgtgttata ccattttact ctctcacaca gtgtgtaggc ctaggctttg tgcatagcaa 720gtgttaaaaa gtaatgtgac tcgtgatagt tattagattt attgaaattc agaaatttag 780ggaaatgcac aataaaatgt acattttgtg attccggtca aattacttaa aaattatatt 840tttcctatga ataattttta tttcacttaa attatgtata acaaaataac atgcataatt 900aaacatttac cacaaagaaa atatttgtac tattgttatc acaataaaga acttgctaca 960taaattcaat tacacttttg tggaaagtat cttcattata taaaaacaat ctacatttag 1020aataggaaaa ttgtacaaaa catgaaaata taaacaaatt aagcgagaat tatctaaaaa 1080gcaactcttc agaatttaga agaattgtct agaataaaaa gaatttagaa gaattatcta 1140agaaacaacc ataaatattc tgatgtattt aagactcata ttctagaatc ctgactatta 1200ttttttatac ttctatggct aatctcaagt ttagctttat ttttctaaag caatgaggcc 1260tgtagaatat tttttcagaa ttctctgagg ttttttcttt tttgtctttc ctgtcatagt 1320atgccaatta ttcatgggtt tatagaatat gtatgcactg ctaagagcag caaaacaaaa 1380gatatatgtg ctatttatta attcatgttg ctttatttaa attacttgaa aatgataaag 1440aaaaaactat tgtatttaca acagcaacca aatatagact acctgtaact acatctaaca 1500gaataaataa aatataacat acaatatgta gtaaatatat ttataatata tatgttcact 1560aaatagttaa cctgtaactt acttacagta aatatatata atatctactg agatagtacc 1620acattttatt aaggattaaa cttttaataa ttcagaagaa taaatataat aaatttcatt 1680tgttctcaaa ctaatttgtt tttatttgtt tgttttttgt attttaattt gacagtagtt 1740ccaagatatt ttggggtata taatgaggtg ataattgcaa agaaaattct gaaaaggaaa 1800agactaagcg tgaattgaaa gtaaaattcg ttaaaaggta taataaactg tgatactgta 1860acaataattg aaaatagata aagaaaaagg taacatcaat aaatagtcta ttatatatgt 1920gaattatgtt aataaaagtg acattttatt ttcaatccac aatttctgaa atatatatgg 1980caatattttt ctgttttatt ttttcaacct ctgattactt tattacattt ttttcttttt 2040ctagaattta cttgtatttt ctctgtgtct aatatatgat tatttctgaa ctagcatcat 2100tggtcctgga accagactat attattccca aggtagagca tcaaaatata acaattaaat 2160aaatactttt agttacttta acaacctttt gtctttcatt ataattttgg aattatagtt 2220tagtacaata cagatagttt taatatctgt tagagtgaag atatatatat atgtgtgtgt 2280gtttttgaga tggagtctca ctctgttgcc caggctggag tacagtggtg ccatctcggc 2340tcacggcaac ctctgcgtcc caggttcaag caattctcct gcctcagcct cccgggtagc 2400tgggactaca ggcgagtgtc accacgcctg gctaattttt tgtattttta gtagagacag 2460ggtttcacca tattagccag gatggtctcg gtctcctgac t 2501692511DNAArtificial Sequencesequence of T3R 69cttttggtgc cctgtccctt ataatttcct cgtgtgtcct ttcccatttg cttatccgat 60gacttgcttc tctcacccat tggattgtga gcctcttgtg gtcaggggca gtgctctgta 120agctgctgtg tccccagaat ctggcccagt gtaggcactc agcagctata gactgatgtt 180aagagaaaat gcacatttca tctcagcctc agagcagttc tgggaaacag ataggaaacc 240aaagctctgc aagaacgtgg gactctctca gggccatcac aacactgttg ttggtctcat 300gtttggtgac tgggtctcct attcctggtc tctttcctag gcataatgct tttatataaa 360gtcccttcca ttgttttttt gtttgttttc ttttttcagc ctaaataact tagtttctct 420aaacttttct cccagggact cttttttaac cctttgaatt attgctgatt attatcttaa 480taacttttat tttttttcca ttttgcatgt catattttag caaagcatta aaaggaacac 540ggcacaaagc acacccatat ttttggatgc tgtggatttc atcatgctgc ttattccatt 600atatctagtc agtacctcca aggcattaat gctgccttac ctccttcatt cgaagacttc 660cctgtgcaag gtggaatata cgtaaggagg caaacagact gggttatatg cctgctctgc 720tttacagagg cctcttccag gagtgtaata cgggggttgc tcatactctg aagaagatag 780tggcaggcta ttactgtcat gagagccaga acgtggctgg cttcttacag acatggcttc 840ataggggcat gccacgtgat tcctgagtaa gccttctggt gtgaattccc tgctcactgg 900ggtgattctt cacttcccac agttcaacct gctgtattat cctcttacct atgcttttct 960gtgatccata gaggtaattt aattttcagt ccatgtacct accctgccta cttagtttct 1020tctcagtgcc acacttaatt ccttcacatt tactgattaa ttaaatgaga agactatgcc 1080aggtgaaggt tcagcatctt cagaactcta catgatgcat tccctgaggc tgcctttcaa 1140taactgaggt gatattcttt gagcagtgtg acctgttaga ggtgcccagt caggtccgat 1200gaaaagccct ctgatttgtt gaaatagtgc attagtaaag tattatagtt tattttcaca 1260aagctagatt agttgttaca tgttggtttt tgttttgcct agccctaaca agtatggagg 1320tgaccttgat gtgtctatag aatatcagga atatctggct gggtgggtgg ctcacacctg 1380taatcccaac aatttgggag gccgaggtgg gcggatcacc tgaggtcagg agtttgagag 1440aggcctggcc aacatggtga acccccgtct ctactaaaaa tacaaaaatt agccaggtgt 1500ggtggcaggt gcctgcaatc tcagctactc cggaggctga tgcaggggaa tcacttgaac 1560ccgggaggta gaggttgcag tgagccaaga ttgtgccact gcactccagc ctgggcaaca 1620gagcgagatt ctgcctcaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaga atatcaggaa 1680tatccatttt atgtctcaac tcacatacct cacagttttc tggtccaatt tttaggcact 1740ttatcaggcc ctcatatgtt ttcaaaaata attgctaatg actttgatga agctaggcaa 1800gatatttttt ggttttaggg cagtttgggc tatagtttgc agccttccta ctttaataga 1860agaattttta aactagattc tcccccttct cagggtggct ttctgccttt ccattctagt 1920gcttcacaca gaaatgacaa gctcacaggg gacttatcta gaaaaggccg agataaaaat 1980aagtacaatg ttaaaaaaat ctatcttata gtatcattta tttagagctt cctctccttt 2040tctaatgaaa ggctgctgta gtttcctttt gtgctttttt tgctgaaggc ttttcagtaa 2100tattcccgtg tgtcccctgt gatgctaaaa gcatgagctt gggggcaggt tgactggcat 2160tcaggtcttt gctcagcctc cagccgcaag acaaggcgaa taatattgat ctcatggagc 2220tgaaatgaaa attaactttt ctaatctgtg aaaatgcttt gttataatcc ttaaatacat 2280gaatacatag gttgaaatag caagtaccaa gtgctgacat tatgtccaca attgccacat 2340gccatgtcct tatgattttt gccagatgtt taataagatt ataaatgaat aggttattaa 2400atgggcatct cctactctct aggtgtttct gtttctgctt ctctgttttc tgtttgtatc 2460tccatttatt ttaatgccta ccattatgtg aagtctgcca ccttcctata c 2511701500DNAArtificial Sequencesequence of T5F 70gaactcaata ggggtcttgt acggagcagg ggcttggtcc ctcgtacctc tggccatacc 60tatggagccc aggggatgct tggcagcacc tgggaggtgc caaccccggg tggcaaggga 120gggccggtcc cacgctcaca ttgtcttctg ttctctctct ctctttatct gtgtcgatgt 180ctctctctct tcccccgtgc ccgtgccatc ctctccaccc ctggattcct gtctctgctt 240ggctttcacc cacttctcct ccccacccac ggctgctcct cctcctgtcc ccacctcctc 300cccgggtgca ggacgggcct cttcacacct gacctcgctt ttgaagccac agtgaaaaag 360caggtgcaga agctcaaaga gcccagtatc aagtgtgtgg atatggtagt cagtgagctc 420acagccacca tcagaaagtg tagcgaaaag gtatgacggc cgcctgggcg gggctgggcc 480tggccgtcca ttccttgtgg ccacagcctc ccgtgggcag aaggatctgc tgagccggcc 540tcacggctac ccgcagggac ccagccctag tgtttcctgc cagtttctaa ccctgggtac 600ttgcactcat gacccctcca ggcccccatc ccagaagact tgactccaac ccaagcctcc 660ttggtggcac ctatgctagt gatgaagatg atgttaagga gatggcagct gtttactgag 720cacctactat gtgccaagca cacgctaagt gcttgccctt actatctgac tcagtcctct 780caaccaccct aagacgtggg tagtgttgtt attcccattt tgcagatggc aaaacagagt 840ctcagaaaag agaagcagag tgtgattcag ttttaggaag gacagaggaa ggggtctgag 900gtcagggcct cctgggcagg gggagctgtc ctagttcctc aaaaccaatt tgcctgaaag 960catattggat tactcacttt acagtaatcc gtgcgtgaga gacaggggcg gtctcttttg 1020agttgtctgt gactttttag atgccttttt cctatttgtc tgcttttggg cattttgagg 1080atttttagcc aggttgtcta aagcagttct tcccagggga gtgcgagaga atcagttgcc 1140tgcaggagct tctccagcag gctaaatcag aggtgccagg ggtgagccca gcctcaccta 1200tatctgaagg acttccctat gctggtgggt ggaggcacat ccaccttagc attgagtttc 1260aaataagcat caatcatctc cattcctttt tttttttttt tttttttttg agatggaatc 1320ttgctctgtc gcccaggctg gagtgcagtg gcaccatctt ggctcactgc aacctctgcc 1380tcctgggttc aagtattctc ctgcctcagc ctcccgggtg gctgggatta ctagcatgta 1440ccaccacacc tggctaattt ttgtattttt agtagagatg gggttttgcc acgttggcca 1500711500DNAArtificial Sequencesequence of T5R 71gattacaggc gtgagccacc acacctggcc cagtggggtc cttctaaaat gcaaagctga 60tcatgtctct tcttccaggc ttaaagccct cccatggctt cctgcagccc tggtgcacgc 120cttacgccaa gcctgaaaac actctgcaca cccacccctt ccctgcacaa acgggcctct 180gcacactacc tgccccggcc atgcccccgc aaccagccct ctctgcttat ctaccttggc 240cttctctctg gtcaagcccc aggcccgtcc ctgcccctag gccttcactt agagcctcag 300aagcacttct tgcaggaagc cctccagact ccagaatggg tccagaacct acttcctttt 360cgtggcattt ctgtattctt tttttttttc ttccatagag ccagggtctc actgtgtttc 420ctaggctagt ctcgaactcc tgggctcaac tgatcctcct gccttggcct tccatagtgc 480tgggattaca ggcatgagtc attgcacccg gcctccacag tcttaattaa ttggttggag 540cattatttgc attaatatct ctcaccaccc tccccattcc tgtccaagac ctcagggagg 600gccaggccag atgtatcatc tgcaccaggg agtcccctgc aggggcttcc agatgtctgc 660taaatgaaca cacagctctc tctggccagt ccaaggcacc ccaggaggcc accagaagcc 720tgcagcctcc ctccctccct cctgctaagc ccaaggaatg agcactgagc agggaatggt 780aatctggaca catccatact ctgcccttca gaaactacct agctgtcacc ctgcacgaaa 840caggcaccag cctgagagtc aggaggcctg ggctctgggt ccacctagac agctgtgggg 900cgcaggacca accgcacccc aatctctaag cctgggtttt tccatacgta aaaaaatgag 960ggcagggcgg gttagacact agaccagatc tgtgatgaca ggcccgttgg aaggctggag 1020gcggggcccc tcgctgaagg aaaatgcctt acctccagaa gtggcccgcc ctggagtggc 1080cagcaaaggg ggcattgccc ctgcgctgga atacacccag aagcagggtg tgagcaggag 1140ctgcggagac cttcagggac aggacagtct agggaggggg tgagcccttt gcagatctcc 1200tgcttatgcc aggagaaagg taaacacctc tcaaacacac aaggagccag ggggctgtgg 1260gctggaacct atagccggca acagcgtata gcttaggatt ttatagcatt gttctaccct 1320agttatgttt cctatacttt tgtttgtttg tttgtttgtt tgtttgtttg tttgaaatgg 1380agtctcactc tgtcgcccag gctggagtgc aatggcacga tcttggctca ctgcagcctc 1440tgtcttccag gttcaagtga ttctcctact tcagccttcc tgagtagctg gaattacagg 1500721199DNAArtificial Sequencesequence of T7 72ccatcttata aatatatcat aatttactga aaaatatttc agtaatgttg aaaggcctct 60gtgccatttc cagcttgagg ctattcctaa aaatccttgc acatgtcttt cagtgcacac 120atgtatacat ttcggttggg tatgcctagg agtggaatga ctggttatag ggtacactta 180cgttgagctt tggtagatac taccaactgc cagttttcca aagttgtacc aatttacatt 240cctaccacca gtacatgagg gttccagatg ctgaacgtcc tcactaatgc ttggtaatgt 300ctgccttttt cattttagtc attctggagg tagtgtgata atatctcatc gtggttattt 360gctttagcct gatgattaac gatcctgacc attttttgga acatttggag atcatctttt 420gtgaagtaac tactcaaata ttttgcccat tttgctactg ggttgttcaa aagattcatt 480aaaagaactt cttttatata tgggtttgta gttgttattt agatattcta gagactagcc 540agatccctat actacaaata ctttctccta ctttgtagtt tgccttttta ctttctttta 600tatacatata atttttcccc ctccaaaaga cagggtcttg ctctgttgcc caggctggag 660tgtagtggtg caatcatagc tcactgcagc cttgaactcc taagctcaag caatcctcct 720tcctcagact ctggagtagt tggaacaata ggcacatggc

attatgcgca gtcaacttta 780aaaaaaaaaa aaattgtaga gatgaggtct tactatgttg ttgcccaggc tgatctttaa 840ctcctggtct aaagcaatcc tcctgcctca gcctccctcc caagtagcta agaatacagg 900tgtgcaccac cacatctagc tttactttct taatggcgtc ttttaatgaa cagataattc 960ctaagtttga tgtagtcaaa tcatcatttt ttcctttata gtcagcattt atatccagtt 1020caagtaaaga atatcatgaa aacattcttc tttgttttct tttagaaact ttcataaagt 1080agcatttaaa atgtgaattt tcctataatc ctagcacttc aggaggctgt gccaccgcac 1140tctagcctgg gcaacagagc gagaccttgt ctcaaaataa aaaattaaaa aaaaaaaat 1199731602DNAArtificial Sequencesequence of T9F 73tgagcatctc tgaactattg cgccatgtat ttccaatttt catattgtgt atttgtatat 60tttatatgta atagtatagg tgtaatatgt aaatatattt tatatgtatt taaaatcttt 120atattttgaa gggttttgtt tcaactatta cttgttaatt tcacagtccc tttctttgat 180gttagcaaat agtaccttca tgaacctcag aggacttgga tctgaatgtg caatgccctc 240tagtatttca aataatagtt cagttggtat agtatttttt taatctgcaa aaaacaatac 300ttgctaatat agctatgtta gagtaaacaa taaatcgaga ataaatttat agcctttgaa 360acaaaacaaa ccaaaaattt tactcctttt tggctttcat ccctgcactg gtatcttaac 420ttctgtttgt ataaaagaat accatttttt cacagaagac aaagaacaat cagccaatct 480aataattatt ttatggccat gctctgaaat acaattaaaa ttatgattgt ggacaatatg 540ccttttcggg acctggctga tggtatttct ggtgtgaccc caactttcca gtcagttcag 600ggcaataaac attggataca ggacagcttt ggggatgaaa tagaattaaa tttagtgtag 660tttttgccac ttttagctgg atgcctggcg aggggttttg tgccctctga gagcctccgt 720cttctcaact gaggggtggt tgtgagtttt gggtcaaatg cttggtgttt agtagatgct 780tggagcttcc atgaaacatg caaccacggc gttgctgcta tttgttcaga tgcgagagga 840acatgacttt tggctgcctg agtgttctca tagcatctgg gccttccttg tgagatcgtc 900agaaagtgtt tcctgcacaa agcctgtact gcggccctgg cgtggggctg attgtcccgc 960tactctgctg tgatggctga attcaaagag tggccgatag gagcacgtat ggtgggtgcc 1020ttgttaacag ctcatagcag aaacgtgaca agcgggagag ggctttgggt tgtcctgaac 1080ttcaaacacc tgtaactgct gcgggaagag cggcacgtgg atgaaacgga cacagagggg 1140gaataggcag gaaaggacgc gggctctttt cgaagcagca ggtctcaagg cggccagcca 1200ctggcgcagc tgcagctgaa gccacggcag agtctccatc cttcccacta tctgctgaat 1260cagagaaagt ggcaggcaac atttttagtg ccttaaattt agaacgcttg ctcaaaatca 1320gaccctactt aaaataagga gcgataccct catttcttaa atagtaaaaa tgccctcagc 1380agaattaacg ggagtatctt ccaacttcat atcctgaatg gaaaagtctg tccaccatcc 1440cgaggacgtg tttgaagcgc agtgtgaaaa tccagcacgt cgtggaccgg ccagacccct 1500gtgccgtgag aggcggggcg gcggggccgt ggggcgctcg cactcccgag ctcatcgtgg 1560catgcgctga gccgaaaacc acgaggtaga gggaatgaga tc 1602741602DNAArtificial Sequencesequence of T9R 74gagcttgatt gtctggccgc gaaaacaggg caggcccgtg tccaacatga tagtgaccag 60ggagacgacc acatccatgt agggcctggg gagagacagg agggagcggt gggctgaggc 120cagcctaggt ggtggccctg cctgtagtcc tgtggactgg ctgatgccaa cagcctcagg 180tgtgggctcc tgccacccac ctcgcctgcc acatcttgca catccccgag gcaactttcg 240atctgctgca ctcggtcacc cgtactgccc aggcaagggc tgcccatacg cactctggac 300aggctgagtg tcctgccctg tcccccacat aaggctgccg gccatggctt ctgcacctgg 360gtgggatgca gacacgctga cctgcctttc tctgcggggc agtggggatg aacccaggtt 420ggactgtggc cttggccaag tgacctgtat atgaaactgg gacaaagccc atctttggca 480cgtagcctgt ggggtggcag gtgctcaggc tttggtgaca aggtggatgg gatgcccaga 540aagggagagc ccatggctga aggcgtgggc aggattgtgg ggaaggtggt tggaattaga 600tgcccagagc aagaatttat tggcacaggt gggcagacag aggtgaccaa aggacaggtg 660taggtcagca ggtggctgct agcacctacc tcactctctg gaacccgatt cccttcatcc 720taaaggggat ctcagaacgt tccacacacc ccctccgcct ccaccctggc cctcacccag 780gctcaccgca cagccaggta gcctggacac acatctccat gaaccacttg aagggtgtgg 840cctccatctt gccccccatg atcatcacca tctcatccgt cagcttgatg tcgggttccc 900agccgagatt gccgcccggc gagctttcaa acatgaagcc aaagtctgca aaaccccaaa 960gagctgcctg tgactgggta ggagccaggg cgggcaagga cgagtggtct gttttgagga 1020gtggaaaagg actcttcaac aggagcaccc cctccacccc caaaaggcag gttgtgtttt 1080cttggagaca gtgatggggt gggtggtggg gcagcaggca gagaaagaga agggaggaag 1140tggaggaagg agccaagctg gggcactgaa cctggaccag ccccactccg cccagctcca 1200gcttctgact cagagcaatg gcggctctcg ccccagctcc ctggggccgg ggccaggcac 1260cctctacagc agaacagctt ggtggccgac agttcggacc tcagagctgg accctgacac 1320tcctggcagg gtggtcctgg gcattctcct ctctgtgggg tggggatccc tatccacccc 1380tgggtgccgg ggtgaaggga gaggagggtg gcgctgtggc tggctgaccg atgtggatga 1440tatggccctt cttgtccagc ataatgttgc cgttgtgtct gtccttgatc tgcagcagga 1500acagcaggag gctgtaggcg gccatgcttc ggatgaagtt gtagcgggcc tgtgcagaga 1560gcgccctggg ctcaaaaagg ccctggggcc tgtgggcatt ct 1602751301DNAArtificial Sequencesequence of T10F 75aatcaaactg gacccttatc ttccaccata tacaaaaatt aatgcaaggt ggattaaaga 60tttaattgta aggcctcaaa ctataaaatc ttaaaaggaa acctaggaaa taccatctgg 120acatcagcct tgggacataa tttataacta agtcctcaaa agcaattgca acaaaaaaca 180aaaactgaca agtgagacct aattaaacta aagaactttt gcacagcaaa agaaactatc 240aacagaataa acagacaacc tacagaatgg gagaaaatac ttgcaaacta tgcatccaac 300aaaggtttaa tatccagaat ccataaggca cttaaacaac tcaacaaaca aaaaacaaat 360aacttcattt aaaaaaagac atgaacagac acttctcaaa agaagacata caagtagaca 420aaaaacatag gaaaaaaata cttaccatca ctaatcatca gaaaaatgca aatctaaacc 480ataatgagat atcatctcac accagtccaa atggccatta ataaaaagac aaaaaacaac 540agaagctggc aaggctgtgg agaaaaagga acacttatac acttttggtg ggaaagtaaa 600ttagttcagc cactgtggaa agcagtttgg agatttctca aagaactaaa aatagaacta 660ccatatgacc caacaattcc attactggtt agatacccag aggaaaataa attgttctac 720aaaaaagaca tgtgcacttg tatgttcatt gcagcactat tcacaatagc aaagacatga 780aatcaaccta ggtgcctgtc agcagtgaat tggataaaga aaatgtggta catatacacc 840atggaatact acacagccat aatagaagaa tgaaatcatg ttctttgcag caacatggat 900ccagctggag gccatcatcc taagcgaatt aacagaggaa caaaaaacca aataccacat 960gtcctcactt gcaaatgaga ggtatatata gacataaaca tgggaacaat ggacactggg 1020gactcctgga ggagggaaag aagtggcagg caaagggttg aaaaactact tattgggtac 1080tatactcact acctgggtaa tccgctagta gggatcattt gttccccaaa cctcagtatc 1140acataatata cccatgtaac aaacctgcac atgtaccccc gaatctaaaa taaaagttgc 1200aattattaaa ataaaataaa aataaagcta gcaatgagcc ctatacatga aaatcaataa 1260aacataatca tggctgtata gaggggcttg tcatttatag c 1301761300DNAArtificial Sequencesequence of T10R 76aattttacac acacacacac acacacacac acacacacac acaatatcgc tcagccttaa 60aaacatgcta ctaatcggct ttaagaaaag aagaaaattc tgtcatttct gacaccatgg 120aagaacttca acattacgtt aggtgaacta attcaggtac agaagaatac tacagtatct 180cacttatata tggaatgtaa aaatgttgaa ctcaaaagta gagaatggaa tggtggttac 240caggccttga gagagagggg taaaggttgg tcaaaagatg caaaatttca gttaagagga 300aggagtacaa gagatttatt gtacatcatg gtgactataa ttgataacaa tgtgcttttt 360tcttgacaat tgctaagagt agaatttgtt tatgggcacc aagcttgatt ccaagtcttt 420gctattgtga atagtgctgc catgaacatg caaatgcgtg tgtctttttg gtagaatgat 480ttgttttctt ttggatatat acccactaat gggattgctg ggtcaaatgg tagttctaag 540ttctttgaga aatctacaaa ctgctttctg tggtggccaa actaatttac actcccatta 600actgtgtcta agtgttccct tttctccatg tcctcaccag catctgttgt ttttttgact 660ttttaataat agccattctg actggtgtaa ggaggtatgc cattgtggtt tgatttgcat 720ttctctgatt agtaaaatga agcatttttt gtatgtttgt cagccatgta tatgtcttct 780tttgagaaat atctgttcat ttattttgcc cacttttaaa tgaggttatt tggttttgct 840tgttcaattg tttaaattct ttatcgatgc tgtatattag acctttgttg aatgtgtagt 900tttgagaata ttttctctcc ttctgtaggt tgtctgttta ctcttttgat agtttatttt 960gctgtgcaga aactctttag tttaattggg cctcatttgt caatttttgc tttcgttgta 1020cttgcttttg gtgacattgt cacaaattct ttcctaaggt caatgttcaa aatggtgttt 1080cctaggtctt cttctaaaag tcttatagtt tgagggttta catttaaatc tttaatctat 1140cttaagttaa tatttgtata tggtgagaga aaggggtcca gtttaattct tttgcatatg 1200actagccagc tatcccagca ctatttatta aatagggagt actttcctca ttgcttattt 1260ttgtcgactt tgttcaagat cagatggctg taggtgtgtg 1300772001DNAArtificial Sequencesequence of T11F 77tctttggggt atgattatat gtctaggtaa aactctttta agaagatgaa gcagagagga 60ttgaattgac aaagacagct ctttaaaaat taaggttatt tcaagactaa gaacataact 120gcttaattgc aggtaataac agaaaaaact tggaaataaa catcccatta tttgacctcc 180aaggcagaag actggcacca aggaaatggc agcttcgtcc ctttcctgtc ttgggcattg 240gtaaaaggag ttgtctagac atgtttgatt tctgtttcag cccttattag tagttatgcc 300atggcaaatt attcaatttc tctgactcag tttccttatt cagaaaatgg aagcataatt 360cttgcctcat agggccatga agattaaatg aggggtgtct tgaagtgtct gggacataaa 420tcttcaataa aagctaattc ctttttttta cagttatctc aaacctttta gtgaattggt 480gcttatcagt gagcttttta ggtgatgcaa agaccctgct ttgctcattt taaggaacag 540ttatttttct ttctccattt tgaagtttct tgtttgctgc ctggttgata tggtttggct 600gtgtccccac ccatatctca tcttgaattg tagttcccat aatccccaca tgtcatggga 660gggacctggt gggaggtaat tgaaccatgg gggtggttac cctcatgctg ttcttgtgat 720agtgagtgag ttctcacaag agctgatggt tttataaggg gcttccccct tcgcttggca 780ctcattctct ctcctgttac cctgtgaaga ggtgtctcct gccgtgattg taagtttccc 840gaggcctccc ggccatgtga aactgtgagt caattaaacc tcttttcttt ataaattacc 900aagtcttggg tattccttca aagcagcatg agaacagact aatacattgg tttaaattag 960aatgccaaaa tttaaataat ttttatcttg aatagtagat ggaattaact ttctcttgaa 1020agatatattt taaaaaattg aacttacaca gacagttttg aaatggtctt attttagttt 1080tatttattta tttattttga gacagagtct cacagtgtcg cccaggctgg agtgcaatgg 1140cacaatctcg gctcactgca acctccacct ccagggtcaa gcgattctct tgcctcagct 1200tcctgagtag ctgggattat aggcgcccac caccatgccc agctaatttt tgtgttttta 1260gtagagacgg ggtttcacca tgttggccag gctggtctcg aactcctgac atcgtgattc 1320tcccacctcg gcctcccaaa gtctcaggat tacaggcatg aaccaccgcg cctggctgaa 1380attgttttta ttatagatgt tgcttgtgca gttttgttag aagttcgtga cttttaacag 1440tgatgaaaat acttcgtcat tcaacaggtt atttttctgc tggttgtagg ttatttgtaa 1500ggaactgtta gtctcctatc tgggtggaca tgtaatagta tcagttactg aaccagaact 1560ttaaacacct ttctgatact cacactggga ggtcaccaag tatctcagaa taaaatgtcc 1620caaactgaac ctaccatgtt cccagaaacc cagcccttct caaattccca gacttggtga 1680atgggagcct gtccttgcag tcttgtagcc caaaacctag ggcttaagaa caccttcttc 1740cttactccca tatgcaaccc atcaagttcc atgcatttca tctcctaatc tcaaatccct 1800tcacccatct ccacagccac cccgctagtc cgggctgcca ttgtctctca cttaaaatgt 1860tgttattgtc taactgacct tcctgaaccc tttcttgcct ctttccagtt tattttccac 1920actacagcca gaaaaagctt ttcaaaatac gcatctggtc acctgcatac ctgtctccag 1980accacataca ataagccttc a 2001782001DNAArtificial Sequencesequence of T11R 78tctgccagcg gctcccgcgc caggtcctcg aagcgcacca ggcggtagcg gccgcgcagg 60aagggtggcg gcttgagtgt ggcggcctcg gcgatgcgca cgtggctgcg gcacacctcg 120cgaatcaggc gcaggtgagg gtcggcctcc acccacttgc cgttggtgcc cagcacgatg 180ccgttgtcgc gtgccagtat cgggcccgcc gcctcccggg agcgcagcac ggcccgcggg 240tcgcgcacca ggtgcacgat gcgcaggttg agcgcggggt cgctgagcag cgggtagagc 300acctgcaggt tgaagaagcg cacctccttg agcaccacgt ggctgtagga gcggcaggcc 360tcccgggcca ggctgaatgg ctgccgcgtg cacagtgtct tgcatacgtc ctgcttgctg 420atggtgcctc ggggaaaggc gctgcaggcg ggcggcgagc acagcgcgcg gctcgttgcc 480cagttgaaaa aggcggacag gtttcggctc tgtggcatgt aggcatcaaa cacgtccatg 540tcgcacaaaa agatagagcg catcaggtcg cgcacggcca tgtgcagcgt tgccgcgctg 600ccctgcgaca gggtggtcca cacatgccac gcgggctcca tcaggtagaa gacgtcgggg 660tgctggctga agagctggcc caagaaggat gagcccgagc gccacgagga cagcaccagc 720acgtgcacac gatcctcgcc gccggctggg gatgagggcc ctggccggga gatgatgaag 780agcaggaggc aggtggtctg tgccaggagg agcactgtca ctgtcttgct ggagaaccgt 840ggcagccaca tgcgggcggc tgggggcctt cgggtggagt gggcaacttt agggacccgg 900gccctcatgc ccatcccatg ccccaattac tgcccagtgc cctcagggat cagccctcag 960attcggctac cctacccatt ggacttccca agactcccaa ggtctcagtc gagcactttc 1020ccaggaatac ggagtcaaga cataggccag aatatagtct gtgctcacag cagaagtcca 1080gttgcagaat aatgtgggat atcatcaaac tgtctaccta cccacccacc cacctactta 1140catacctaca ggctatctat ctgtagagag aaatactatg tttcaaagag aactcctgtc 1200ttttgcttca ggatacctct tagagagacc cttttaggtt gtggagctaa aagggcttga 1260tgggggcttc ggtggatgtc agagcaccac caggctcgcc gaggttgaat cctggctctg 1320ccacttccta gcctatgatc ttgcttatga agatcactta aatctctctg tgacggatca 1380ctttacccgt gtgtgaaaga gggataattc cggtacctgg ctcacaggat ctggggggat 1440tggggggtta ttataatgaa gatgggggaa gggaacacgc agtcatgccc ataactgagg 1500attgcacctt ttacaaggtg tgcttctgta ttatataatt tttttaacag gcaggtataa 1560aacttttgtc agccaggcgc ggtggctcac gcctgtaatc ccagcattat gggaggccga 1620ggcgggcgga tcacgaggtc aggagatcga gaccatcctg gctaacacag tgagacccca 1680tctctactaa aaatacaaaa aattagccag gcgtgatggt gggcgcctgt agtcccagct 1740actcgggagg ctgaggcagg agaatggcgt gaacctggga ggcagaggtg gcagtgagct 1800gagattgcgc cactgcactg cagcctgagt gaagagtgag actccgtttc aaaaaaaaaa 1860aaaaaaacaa caaaaaaaaa acttttgtca ttaaagataa acaagtaaat aaagtggaca 1920aagaacagca actgttgtca tcactggtgg ggagtgaagt gctgtaggca gcatgggctc 1980cagaaggagg gtgtcctgga g 2001792100DNAArtificial Sequencesequence of T12 79tggcatccag catggagccc acagcttccc tttgtagaat tgcccagttg ttgcagagtg 60ctttggtctc aatgggtcta aagctcttga tgatataaga gcttcaactt ccttttccct 120ctcctccccg caggctgcac aatgtcctgg tgaatcacct gggacttcag agctctgcca 180ccctgggtgt gaagctcagg tctgctcttg gtagcttggt cagtgtgaag tacaccgtga 240ttttgggcaa gctgcttaac ctccctggcc ctccgtttcc tcatctgtag aatggggata 300ttcacagaac ctacttgtag ggccatggtg aggattaaat gatgaacagt gctggcaaac 360aggaaatgct atataagtgt ccctagcaat atacacaccg cacatcctca gtcaccacgt 420gtgttcactg aggtatgggc catgtgtggg tggaattgtg ttccctaaaa agatatgttg 480atgtgctaac ttgaggtccc tgtgaatgca ggaaaccaaa atatttcttc tcaaaatagt 540gaggattgtt aagttaaaga cactgaaaat gcaggggaac actgccttgg cctctacttg 600cctgatgaca ggcacgaatc cttccttact taagacacat cacttgctta tcagcccaga 660gaaagcacct gcaggcacca ggaaaatcta ggaacagatt ttactctctt cccacatttt 720cccacttttt caaacactga aactgctctc tcctttgtct tgtcactaga taggatttat 780ggctctttgt taaaatattg tttaagcaag gcttctacgc cactagcttg agagagaaat 840acttttgaac tgaggcctct tccgcatgat aggcagagca tgcattaata catttctgct 900tgtttctctt ttgttaatct gacttttgtt ttccagagtg tctcaaataa gaacataaaa 960gggaggggag aaattatagt ttctccccta catgaactta ttcggatata gggtctttgc 1020agatgtaatc aagttaagat gaagtcatat ttgattagga taggccctaa ttaaatatgg 1080ttgctgtctt tataaaatga gaagaagaga ccaggtgtgg tggctcacac ctataatccc 1140agaactttgg gatgccaagg caggaggatt gcttgaggcc aggagtttga gactagcctg 1200ggcaacacag caagactcca tctccaaaaa aattaaaaat tagctgggca tggtggcatg 1260cacctgtagc cccagctact tggtgggctg aggcaggagg atcaattgat cccaagagtt 1320caaagctgca gtgagctatg atggcaccac ggcaacctgg gtgacagagc gagaccctgt 1380ctcttaaaga agaaaaaaag aggagaaaaa aacagagaca cagaaaaaag tccttgggat 1440gataaatgca gaaattggag ccatatatcc acaagacaag gaaccaccag gattcttggg 1500aactccagaa gctaagaaga gggcatggaa caggttctac cctagggcct tcagagggag 1560cgcagccctg cagacaccct gagttcagac ttctggcctc cagaactgcg aaagaataac 1620tttctgttgt tacagcagcc ctaaggcact agtacaggtg acatgtattg ctcttctgaa 1680gagcagggtg tctacagcgg cagaggtctg ggtcctggca cgtgcccttt aggattccaa 1740tatccttagg ggcctgctgg tgctgacagt tccagaacca taagacagaa ttcctgcggg 1800ccagtttgga agcagagaca ggaaactgga agagccctta gcctgtgctt gggcttaaag 1860ccctttagct tgtggcttta actctgaaac ttctagaggg catcttgcag gtcagtgtga 1920ggtacagaag ttgtcacaag cttcctggct caaagaaagt gagacttcac gaacttttct 1980ggacatcaca ccagcactta tgaagttatc ttgttaagca cagatgaaat cagaaataca 2040ggcattcacc atcacttaaa caaagctcag attgtagagt gcgaggaaga atcggtggga 2100801700DNAArtificial Sequencesequence of T13F 80cagatctcta aagtattggg tgtggactag agctctggac ggcctaaagg aaaggaatgt 60gccggttcac agggacccgc ggctaagctc aagggtaaaa tacagcttta caaagcatct 120ttaggctgtt ccttcccaaa cgtgcttaga agggaacagg gaaaggcggg tgtgttttct 180cactgaggtt cttctagtgg ctggaatctg atagagtacc aagttgtagg gatatggata 240tattttccct ttggcactcc ataaagctaa atgttgggct gaaaaaagga tgcagcctat 300aaacaagtat ttttcctgaa accaactgca tgaggaaacg ctgcgctccc cctcagggag 360cagtttctga agccagctga gcacagctgg cactggccag agggagccct ccaccctccc 420accacgtatg cccacctgca aacctgggtt ctgagtcccc atgcagggga cagacctgaa 480aattccagtt tgtgtccttt caggtcatcg acaggaatga cagcctggca agctgcagtg 540actgcacaca gctaccctgt gagctccact tgtgtgggtg caggtgggcg acaggagtgt 600gtgacacaga caggcactcc accaggagga aacccacagc agacgtcaac catcgcttta 660ttaaggctgc gagtcggggg gctgagtcat gcactccaca gacaccccca ctgctcccaa 720ggtccacttt tggatgaccc tgaaggcaga gactcctgag atctgggcca caatctaggg 780tgagccaccc acagtgccct gctggacagg ggggtatgcg gactgcacgg gggggccctc 840agcaggggtc ttcctgccta gggtggggct ggctccagtg ggtcctgggc tcaggcaggg 900ggggtggcag ggaggcaggg acatcccccc gccctctggc ctatggcttt gttgccctat 960tgccaccagc gcagaagcaa tgtgctatac cgtgaggtga tgaagaagag ccccgggagg 1020gagcaggcag ctctgtgcct ggggcctggc cagacctcag gggtgctgtg gccctgctcc 1080tgttccccct cagctcctcc cagcaatggg tctcctccag tggaggtcag tcactcagaa 1140gtggacccgc agcacgtctt ggctagcaac cggccgctgg caggctgtgc acgtcatggg 1200cagggagcgt tgcttctcac ccaggcaggg tcggcacagg aggtggccgc agggcagctg 1260gtacaccggc tcctttttga agtagggaga aaatactctt ttgcaggagg cacattcggg 1320gcccaggatg ctcccaggct gctctggtaa atcaggaagg aaaacaggcc agggttagga 1380aagctgctcc atggtccagg ctgctctgag gggcagagcc ttcccaccgt gctgctgcag 1440catctggctt catccctccc gagtccatcc cagtctgatc aggtagggga gtggaagcgg 1500gagagggagc ctgggaaccc gggaggcctc ttctctatca tctttgacca aatctcagtg 1560cctctacgaa tgcttgagaa gagctggctt ctgagggcag caggcaggac tgggcccttc 1620ctcctggtct cccagcaagg tttactttcc cctgcgatag gtggccaagg ctggagcaag 1680gcacagctca ctctgacaag 1700811701DNAArtificial Sequencesequence of T13R 81gaatctgacc actcagtccc acatcccagg attcagagaa aaagaattcc agtgagggct 60ctggacccca cacagctaag gcttccaggg tttaggcaag ccctgaggga cacccatcat 120aattacccag acgggggccc agcatcccgc cccagcattc tgccttgcaa ggagctccct 180caccagggct cagggaaggg acagcctgca gttccagcaa gggaggcctg cagagtcagc 240cacaggtggc cactatcggt tgcttggtgc caacttagtg tgagggggca gggcccagac 300tcgagggtgc cattaccgtc ccccatcgtg tacttctttt cctcgtagct tgagtctgtg 360tattccagga gcaggcggat ggaatgggcc agctgggaga gatggcccac agctcgggtc 420agagatggag ggtccctgac tttgtgacga ctctgcacaa

ggggagcccc atctcctcct 480ctcgttcctg cctcacccgc ccccaccccg cacgcccagc cacacgcaca gacagcggca 540agcacagacc ccgctgtcag ggacagccct gaagaggaac cgtccctaga gcccgtcctg 600cagctgctcc acacttcccc gcccccacgc acccccgtcc caccgcccag cggaccctgg 660ctcaccccgc ggatgttcca gtaccccagt gtcatgggca tggtgctggt tgctgtggat 720tctgcagaca ggcctcagcg gggcggggct cagcgtttgt gagaggccca gagagggtag 780aggggaagcc ttgctgcgac cccgccccac ggcccgccct gcccccgaaa cgggccaatc 840tggaggcctg gagcgcgctc atggggctag gagtaggatc tcctcccacc tcccagcccc 900gtgggtttca ggagagagat caggacgccc agaagcccag ggcgggggag aactggttga 960gtccaggggt tcaagactga actgagctat gatcgcgccg ctgcactcta ggttaggcaa 1020gaaagaaagg ctctctctaa aacagagaga ttctgaataa agtaataata gcctaataaa 1080gaaaaataac acaaaagaac atttggtgct cagggattca ctggataagt tttcaaaact 1140tttcaatgta tgatagagat tgttataaac tgcggacata cgtggcatga cagacctaac 1200gtgggaagga caacacaggc aaggatgatt ataactcact gtcacttatc agcctaaatc 1260caaacgtcag gaataccgcc tcagagaaaa gaaaatgatg tttttgtcat aagtggtgct 1320gtgctcctag ggagcttgct gggtgggaag agagacagaa aggtggggag caggggctgg 1380tggacttggg gagggaggag aaagcccatg tggaaacgtt agaatctggg gtaatcagag 1440gtctttgtat tcattcgttt tgtaaatttc tcaaactctc atgttaaatc aaaataaaaa 1500gttaaaaaaa aaaaactacc aggacagaca tacacaaata ttattaactg aaataaatgt 1560tccatcaaaa aggacttacc ttaactacat gagttatatt atgatttcta ttattattat 1620tattattatt ttaatattag tatccatcca gcacaccact ggtcttcaag tggaggtaac 1680tttgcccctc aggggacatg t 1701821482DNAArtificial Sequencesequence of T14 82atcagccccc acatgcccag ccctgtgctc agctctgcag cggggcatgg tgggcagaga 60cacagaggcc aaggccctgc ttcggggacg gtgggcctgg gatgagcatg gccttggcct 120tcgccgagag tnctcttgtg aaggaggggt caggaggggc tgctgcagct ggggaggagg 180gcgatggcac tgtggcanga agtgaantag tgtgggtgcc tngcacccca ggcacggcca 240gcctggggta tggacccggg gccntctgtt ctagagcagg aaggtatggt gaggacctca 300aaaggacagc cactggagag ctccaggcag aggnacttga gaggccctgg ggccatcctg 360tctcttttct gggtctgtgt gctctgggcc tgggcccttc ctctgctccc ccgggcttgg 420agagggctgg ccttgcctcg tgcaaaggac cactctagac tggtaccaag tctggcccat 480ggcctcctgt gggtgcaggc ctgtgcgggt gacctgagag ccagggctgg caggtcagag 540tcaggagagg gatggcagtg gatgccctgt gcaggatctg cctaatcatg gtgaggctgg 600aggaatccaa agtgggcatg cactctgcac tcatttcttt attcatgtgt gcccatccca 660acaagcaggg agcctggcca ggagggcccc tgggagaagg cactgatggg ctgtgttcca 720tttaggaagg atggacggtt gtgagacggg taagtcagaa cgggctgccc acctcggccg 780agagggcccc gtggtgggtt ggcaccatct gggcctggag agctgctcag gaggctctct 840agggctgggt gaccaggnct ggggtacagt agccatggga gcaggtgctt acctggggct 900gtccctgagc aggggctgca ttgggtgctc tgtgagcaca cacttctcta ttcacctgag 960tcccnctgag tgatgagnac acccttgttt tgcagatgaa tctgagcatg gagatgttaa 1020gtggcttgcc tgagccacac agcagatgga tggtgtagct gggacctgag ggcaggcagt 1080cccagcccga ggacttccca aggttgtggc aaactctgac agcatgaccc cagggaacac 1140ccatctcagc tctggtcaga cactgcggag ttgtgttgta acccacacag ctggagacag 1200ccaccctagc cccaccctta tcctctccca aaggaacctg ccctttccct tcattttcct 1260cttactgcat tgagggacca cacagtgtgg cagaaggaac atgggttcag gacccagatg 1320gacttgcttc acagtgcagc cctcctgtcc tcttgcagag tgcgtcttcc actgtgaagt 1380tgggacagtc acaccaactc aatactgctg ggcccgtcac acggtgggca ggcaacggat 1440ggcagtcact ggctgtgggt ctgcagaggt gggatccaag ct 1482831680DNAArtificial Sequencesequence of T17 83ggcgccacta cgggattaag cctgaaaccc gagcggcccc ggcccccgcc acggccgcct 60ccaccacctc ctcctcctcc acttccttat cctcctcctc caaacggact gagtgctccg 120tggcccggga gtcccagggg agcagcggcc ccgagttctc gtgcaactcg ttcctgcagg 180agaaggcggc agcggcgacg gggggaaccg ggcctggggc agggatcggg gccgcgactg 240ggacgggcgg ctcgtcggag ccctcagctt gcagcgacca cccgatccca ggctgttcgc 300tgaaggagga ggagaagcag cattcgcagc cgcagcagca gcaacttgac ccaagtaagt 360gcaaaagaaa ttgccccctg atttattgct gaaacctgta aggctcgaat gtgcaaaact 420gatagtttta ctaacctata aaaacgtcta gacgcctacc caagcctagg cgaacaacat 480gcatccataa aaagagcttc ccataaccac ctaccctggg cgctcagtta gtacggtaaa 540cagagcgcga gcattaaggc tttttatgat aattccccac aagttgtgaa aagcgaccat 600ccttggtgaa attaatttaa cgacctctct tccccaccct gtggtctctc cctgcctccc 660ctcctctcct ctctccccgt ctccaaacct ccctctttgt agacaacccc gccgcgaact 720ggatccacgc tcgctccacc cggaaaaagc gctgtcccta caccaaatac cagacgcttg 780agctggagaa agaattcctc ttcaacatgt acctcacccg ggaccggcgc tacgaggtgg 840ccaggattct caacctaaca gagagacagg tcaaaatctg gtttcagaac cgtaggatga 900aaatgaaaaa gatgagcaag gagaaatgcc ccaaaggaga ctgacccggc gcggtgctgg 960cgggagcgct caagggcagc ggatttgttg ttgttgctgt tttcctttgt gggtgtttgg 1020tgcttgattt ccagaaactc tccagcgact tggacttctt cttctttttt tttttctttt 1080tagatagaag tgactgtgtg gttggtctct gaggtatttg ggggactctg tatttgctcg 1140tttacgtgtt ggaaaaacca agtggctttg gggtttcgcc ctatcccact ccctctcttt 1200cctgctccat tggttcctta agaaatgcta tattttgtga gtgcaagctg gcttggggag 1260ccctctcttg tgtaaatgtc ccccatgttt ctgaaaagtg ctgtagttta gtcccctcac 1320ccccagcact gcccaaacag gggccaagtg cgccccaatt ccaagaatga aggcagagcg 1380acaacagtgc ggacaccccg gctgctagcc cacggtgaag cccggcgggg ttgcccacca 1440gttgcgaaag ccccctttcc tcagggagca cgcgggacct cggtggagat ctccagtgag 1500gcttagagga gcccagggcc tcgggcgggt tggggtttgt cctcagtgca ttggacgcgc 1560tgctctctcc cctgaaggct gggctcgcgt gggcggccgc gggtggtggc cctcccggtt 1620cctgcccgag gaccagttgt aaatgttact gcttcctact aataaatgct gacctgatca 168084919DNAArtificial Sequencesequence of T18 84gatcatctac taggttgaaa ggagagaata tgacttccag aacagcactg atgcttaaaa 60aggatgcctc tggaagaaaa ggaggaagag gagcaagtga tgggagaata cagtgggact 120ttgggcacca tagggtcatc ctgagttttt caccaaaatc aggaacagcg gcaaaactgg 180tttcactgaa gaagacacac gtttggagac atgtgtagtc tccaaggatt ctcacttaac 240aaagcctatt tctgttgtta aaaacccctg cataatgcac ccacacacaa acacaaggct 300tggtctgtgt tcctggccac ctaaagaaac tgattcccag taagtttaaa cctgaatgaa 360atgtttctgc aaattcagcc tcaaaattcc tcctctacct ggcatccctg gcttgtaaac 420tatgtgtctc attagttcat aaacaaagca gccctgactt tgccttgtac tcaaccacag 480ccctaggagc cagtagaatt tgtccagagg tgctgggctt tggagcccaa gtggacaaag 540tcagaccccc tttcctcagg gcaaagccct cccacagggc tgggacccca aaggctatgc 600tggaagcagg ttcagcagca ggatatcaag gggcaaagct cctaattcaa aatcttcctg 660gcttctgaac aaccattagg atggacagag aaaacttttg ccctgctctg agagggtccc 720acagggcttt tggaagcaga gccaccattg agaaatccct ttcaacctga gtagtaattc 780agatttttct cccactcctg cacaacttaa tttgctgaat ggaaaattca gccagaagtg 840atgggctgct tgaaatcaac aaaacttgac acattcttcc cattttcatt ttactttatt 900gttaaacaca taattgatc 919851174DNAArtificial Sequencesequence of STAR A1 85gatcaataga agaatggagt ttgtgtttgc tagccatagt tttgacgtgt gggagagttg 60gagtctagaa ggttctctgg acgaatgtcg gcttgttaac tgcaggaatt cctctgtaag 120tctctgtcct tacagaaaat ggcccgaaat tgaaaaaccc tacttcttgg aaaacagaaa 180taatttgtgt aatgaatgtt gcaggcggtg ttggacgttc gtgtggagat attggcaatg 240gtaggagacg atggtatcac acgttggatc gattaaaaag aaaaacagag tctctccatt 300tgtgagtttc tctcttttaa ttacttttgt tactttaaca tccttaggat tcacagacga 360aaaacagaga cacccaattt ttgtgtttcg agactgtgtc gtgtgttgtg tagttggtat 420caaccaactt atatctgtaa tcattgtttc tttttattta ttctcggttt gcagaaacat 480ccgatgagct tgtcttagag ggacgtttgt tgttgttttc tgggtctggt cgtgatgaac 540tcgaaagcat tgtgtgtttg gttagtagtt tgaaataggt gtgtgtattg tatttgtata 600tgctgcgttt gtgttttaga gatcatcgta cataaaacac atcatcgtac ataactaaaa 660tttgagctaa actacaaaag aaagtaacct tcatttttag tcgaaccagg ccccagctag 720gcagctatct cgtaaataag attgctggct tacgatcgta ttccacgtgg caatttatgt 780gccgtggatt taaatttgta cgtggcatga gtgttaggag aatgtccaca tggcttgtag 840ttgttagtcc cacgctctga accagagcaa ccggctcctt acacgtgttc ggcttaaatc 900catttttcga atgagattac acttctaacc ttgtctccct ctcccgctta taccaccacc 960actctcacac aagtctctca agtcacaaac tctgtttcaa accaaaaggg aactttgtgt 1020gtgttgtcga gttttatggt gactgtaaac cctagccaag ctcattgttt gcctatgaaa 1080atgagtctac cgggtttcaa tactcttccc cacacggcaa caacgatacc ggtttccata 1140cggagcaata ggacgatgtc gttttttgag gatc 117486910DNAArtificial Sequencesequence of STAR A2 86gatcaaaatt ttggtttctt cgctttgatt ttcttcttct tcttcttctt cttccctcaa 60gttccttaga atatctttct catccatttt ttttggttct tgttttgtta agtgaacatt 120ttagttgatt ttaaagtgct aaacttaaat gcagcatttt actaatataa aattacgctc 180cattattgac cttatataca tagaacaaaa taatgttata atcttcgact tttttctaac 240aaatattaac caatcatgtc actaagaaat taaaaaatac tagtatatag gaatctagtc 300cattgtatat atcgtaaaca tggacacttc accaacgaac atgcatgggg tctttttata 360aggttcttta taccgaaacc attgttttgg tttttatgat aattgagtta gttttgtggc 420ttttccgttc aactaaaagt ctcattatgt caactgctat taaaccggcg cacatggcat 480gttttatgaa attaaggtca attggactcc aacttttcaa ttattaaaaa aaaagaaaaa 540tgattgttgt atgccttggc gaagaagaaa agccgctagc tttattcatt atcaaacgaa 600acaaaaacaa caacacatca ctaagaatct taaactctta accttacatc aaagtaactt 660ttattacatt gcatacaaga aaagaacaaa ccagcattat taggtttgag attaaacctg 720ttcccacaca tatacataga gatatgaact ctacaatttc aaaccagagc cttgaagttt 780ctcctcaaca atcatgtcga ttttgttttc catttcagga gtcatataac tcttccaatc 840accaacttcc cctttacgga aaaaactctt gaaacttact ccttccgaca agcttcctgt 900tttgttgatc 91087906DNAArtificial Sequencesequence of STAR A3 87gatcattaat cgcagatttt tacaagacag cagcttggag agcaacttac aagtgtgtta 60taaactctga actcaacttg gaagatgttg acgttccaaa tgaaattgga agacaaacta 120tcttcccacc aaggacaaga aggccgtctg ggaggccaaa aaggctacgt atcaaatcca 180ttggcgaata tccggttcgt atttgtagga gtcccatttt ttcgacttta tctttattcc 240gtatttaatt ttcaatttta tgtggtttaa cagaaatcaa agagcgtgaa ggtgaagatt 300aacaggtgtg gcagatgcaa aaagactgga cacaacagga caagctgtag taatccaatc 360tgaagatgtt ttaaaatcgg ctatattgat agaacgatga ccattttatt attgtttttg 420tgtttggaaa tggttatttt tggataaaat atgttgcatt ctattttata attttagttt 480cgacttatta catataaatc tagtaaggta atatattagc aaattacaga taatgatgaa 540aaacatggac aggtataggt ggataagata taaataaggt aggactgaat tgttacccgt 600taataatgaa agaatatacg aaatactaaa cattaaataa ggaagttact aattattgga 660caacaaaaag tttaattcct ttaaaaagaa attggaatac agacagtttc attgacctaa 720ttaagtactt ctttgaaaaa aatcaaacta ggagaataga agttgtaaat aattgaaggg 780aaacgtcgat tcggtgaaaa ggttttttaa ttagtattta aagggaaata tcttctctta 840tacagaatat cttgccccag aacaaatcgc ctcaaatact aaaagtgtgt acatcttctc 900ttgatc 90688782DNAArtificial Sequencesequence of STAR A4 88gatcaaattc atatgcttat ttgtgattat actttgcttt gattcaggaa atcaaagaag 60atagctccac cttacagggt gatactacac aatgacaact tcaacaagag ggaatatgtg 120gttcaggtgt tgatgaaggt aatacccggc atgactgtag acaacgcggt taacattatg 180caagaagctc atatcaacgg tttggcagtt gtgattgttt gtgctcaggc tgatgcagag 240caacactgta tgcagctgcg cggtaacggc cttctcagtt ctgttgaacc tgatggtgga 300ggctgctgaa actaattaaa ctcagtatag attttcccac cttccaggac tctctattta 360gtcaaaaaca tttgttgttt taatgtatat aatatcagaa atttggtaca agactgttac 420tatatgcaat gaaccttgcc cctacataga tctgttgtga gttttaagtg ttttcatttg 480gaacttcaga atgcaaataa acaaaacttt attgaagtca aatggtgtta cagatgaatc 540tttctgattc tgtaatcact aatgtaaatg tatctaagca attgtaaggg agtgacgtgt 600ttcggtttca tctcgcccaa aaaagcattc aaacccaaga aacctgcagt ttcaagacat 660tgatgggata ccatatagat gtatcaagca tcaaccggag taagaagcga ctgaatgccg 720aagataatga aaagcattcc accggaaaga gccacctgca acaacataag agctatttga 780tc 782891356DNAArtificial Sequencesequence of STAR A5 89gatcctgtaa aacataaagt tagagataat tgtccgattt gtttgccctt ttaatttgga 60gagatatgaa ccaaaaacat atttcggaat gggtcccttt ttcatcgtgt gtaacagttt 120taccaaacag taatactttg tgaaagtttt gattaattaa tgcaaaaaga ttagaaaaaa 180gcgaaactaa tttttggatt acactagaaa aaggttaaaa tcaataacca aaaaaagaaa 240aaggttaaag ttacaaaaca caccggttta tagagtgaaa tgattattgt tctgttgaat 300tgacgtgcca gcttagcatc accttactat tatcagtcac ctatatatca caattcacag 360gcttcttgct ttctctcatt ggctcgtctt cttccctttc ttctccaatc accttagctt 420gctgatcagg taaactagat tggtgtttcg tgttgttttc ttctcaactt aggtgtttga 480tttgagaagt ttttctatgt atgttggcat gttgcgttcg tagcattgca tatcaacgga 540taggtttgaa taggtagaat taatttgatt gatatatgaa agaatgtttg tatatatact 600ctaggtctag gttattgaat attgagaaat ttattttgtt aggtttagat gaattattct 660tcgatgagtg gttcaaagtt caattggcaa gtcttttcaa tgattgtagt attttggtga 720tgataagtaa gttgttaatg actctcaagt ctgaattcat gttttggttt tgtttccttg 780taaaaatgtg aacgtttttc ttacagaagc tttcacaaac aaagtatggt taattgagtg 840actaatccac taattctctt ttgttgtttt atatcgttta ttaggtaatg tttttttttt 900ttgggtgtgt aaaatatgat actgactcaa gattttatca tatttctgaa tccataagct 960aaagtacatt tgagagaagc aagagagata gaatggggcg tggagttagt gcaggtggag 1020gacaaagttc tttgggatat ctttttggga gcggagaggc tccaaagcta gcagccgtta 1080acaaaactcc agctgaaact gagtcttctg ctcatgctcc acctactcaa gctgctgctg 1140caaacgctgt tgatagcatc aaacaagttc ctgctggtct caatagcaac tctgcaaaca 1200attacatgcg tgcagaagga caaaacacag gcaatttcat cacggtatgt ctttaattct 1260ttcgctgaat cgagtcctgt gtgctggtta tcggatagca aaaacatctg tatctttact 1320tttcttagat tagttgtctg aaaatgaaag aagatc 1356901452DNAArtificial Sequencesequence of STAR A6 90gatcgactgg tacaatgcta gaagccctag aggttgtagg tgatagccac gatacatcct 60taggtgatgt aagtcaactg aatataaatg gccatttacg tagacttcat gtcctagatg 120atccctccta ttataacgtg aatctcggtt tcttggtgtg gaaaacgaaa tgattgatat 180gtttttgtca gggatttgag gtggtgaaca gtcgttatat gactagttat gatgatgaag 240atacaccgcc aggaagtgga ttcaggacaa aactaagaga gttccataag aggtaaatga 300cgcattaact catgcctctc aacattttgt cggcattcaa acagatgcat tcaagtctct 360tttaataaac acaagaatcc catttgttta ttgttttgtt tgtatgcagt gcggcatcat 420tcacagaact agataggaat tacctaacac cgttcttcac aagtaacaac ggagattatg 480atgatgaggg taacatggag caacaccatg gtaacaacat aattctctga tctcttgttt 540cactattatt tttgttgtta ttccgcaccc aaaaccatga aatttacaat tggggttatt 600gcagaagaac gaatcccatt tactagaaga ggaaatctaa ataaccgcgg ctaagtttcc 660gagatgagaa atctaatagt gttttttcag cggcatatat atgtacataa aacaaactgg 720atgtatggga ggaggtagtg acaaaggatt tgttctaagc taggtttctc tataatatgg 780tactgtgttg ttggtgtaaa cctgaatgga tattgttagg ttgaaactaa ttacattcac 840acaaagaaag aaaaaaactt gaagaaggcc atggctggtt tatactgaac cacgaatttt 900gttagtttta aactcttagg gaaaatgcta taatgccttt tttgtcttgt agtcgtgttt 960ggtttgaatt aaaaaaaaaa tagagaacgt cacggcacgc caaaagtgtg gaccttgttt 1020attcgccgga agtaagtaac caaaaacgct tctaatcttt cgtttacaac aaatatctct 1080ctctctctcg ctctctctcg ctctctcttt cttcttcttc atcttctttc atggctgtta 1140ctggctgggc aatcacaatc tgaattcttt cttcctcctt gtctctctga ttttcgccga 1200gttttggggg ctcttgttgt tacacgatga gtctggtggt tggtcagtct ctgggtttaa 1260ctctagtcgg tgatggtctt tcgttacgca attccaaaat aaatgtcgga aaatcaaagt 1320ttttctcggt aaatcggagg agattggcgc gtgcggccct ggtacaagct aggcctaagg 1380aagacggagc ggcggcaagt ccttccccat cgtcgagacc ggcgtcagtt gtgcagtacc 1440gacgagctga tc 1452911085DNAArtificial Sequencesequence of STAR A7 91gatctatctt atattgttag ttcatgtttg tttttaaaga ctgtttttat gtttcaatgg 60tatattactg actggggcag taatattgtt gaagtctgta gattatggtc gcatggctga 120aatactggtg cagagggctg cttctcctga tgaattcact cgattaacag ccatcacgtg 180ggtaagcaga ataaaccatg cttctgcttg gcgtcttcca gttatataga ttggtactat 240tttgacttct cgggagattc atatactaag aatatctgct ttttattaaa tgttgtagat 300aaacgagttc gtaaaacttg ggggagacca gctcgtgcgt tattatgctg acattcttgg 360ggctatcttg ccttgcatat ctgacaaaga agagaaaatc agggtggtaa gtttgcttct 420cctcctcagt gatggaaact gtaggttttg tatgcatctt tttactttct ttgttttttg 480atttttattt gcataaggtt gctcgtgaaa ccaatgaaga acttcgttca atccatgttg 540aaccctcaga tggttttgat gttggcgcaa ttctctctgt tgcaaggagg ttagtttttc 600tctattgttg tttttatatc cgtttgaata ttattaaatc gcgcctgttt atttgtgagt 660ttttgcattg agcaggcagc tatcaagtga gtttgaggct actcggattg aagcattgaa 720ttggatatca acacttttaa acaagcatcg tactgaggtg aagaaactgg tttttgcttg 780ggcatcattc ttttctagtt agcctttttg tttatcgcgt tatagctaaa ttggtaatgc 840tgcaacaggt cttgtgcttc ctgaatgaca tatttgacac ccttctaaaa gcactatctg 900attcttctga tgacgtaagt tctatctccc tgactgttcg tttgattggt tggtgaactt 960tataatataa aggtttggtt ttgtctagta ataaacttat ttgatatttg aactatctgg 1020acttggaaat atactttagg tggtgctctt ggttctggag gttcatgctg gtgtagcaaa 1080agatc 108592696DNAArtificial Sequencesequence of STAR A8 92gatcatcttt ttctaggtag ggaattgctt atctcggtaa gctaagaatg ttagaaacaa 60agaactagga cagaacggga aatggagaag gaggttagaa tcaaagaaca gtaaatggag 120aaggaggtta atgtgtattt cattctatct acattttaac taattgagtg tatccagtct 180tatccattaa tgtaattaca agaagaatag taccaagcat gtaggttata gttttcactt 240tactgggtga aggtttctgt agttcaagtg ggtcaaaagt ggtttgcgga aacatatctc 300taataatttg attgagaggc tcctcgcact cacatggact taaacttttg tgtattatac 360aaacatgatt cacatacaca tctcgtgtat attgcaatac atttggtaaa ttatctgaaa 420ataataatga aggtttcttc aaaagaggtc caggagctat ttccattaac actgttatac 480tgaacagtat acaaaagaag actgcagtgc gagaatttat ggaggatgat aatgcatttg 540agatattctt ctgaacactt tcatatcttt tatgtaaaac atttttgatg agaaaatcac 600cagtagtatc caaacacttt aatccagatg atgggaaaat gctttgttta aacctactac 660gaagtatgct taatacttca ttattaccag ttgatc 69693925DNAArtificial Sequencesequence of STAR A9 93gatctggttt cggtaattgt tgtttccggg aattgagtat agaaacacaa atacatattt 60aaccctgatg aaagagggtg taaacttgtg cagatagatg cgaaaacaac gcacgacaaa 120cttgtgaagt tggtgctcga tgataaagtt agacgaaatg ttgtatctct tattgttttg 180cgacaaattt acatgtcacg gctgagttat atgcttaagg gaagatgaaa agttcagtca 240atttacatgt caccactgag ttatacgttc caggaaagac gaaaggttcg atagaattac 300attacggttg agttatatgc ttaagggaga acgaaacgtt cagtcaattt acatgtcacg 360gctgagttat atgttccagg

gaagacgaaa ggttcggtaa aattacatta cggatgagtt 420atatgtttaa gggaagacat ctataaattt acatgtcacg gctgagttat atgttcaagg 480gcaaacgaaa gatgagtgta aattatatgt tacggctgag ttatatgctt caaggaagac 540gaaaggttcg gtaaattaca tgtcacggct gagttatcat tcagggaaga cgaaaggttg 600tgtaaattat atgttacggc tgaggtacat cacgttaagg ctgagttata atacagatcg 660gaaaacaaca tttttctggg gaagacaata tgaaatttat tggccaaaga acaacaatca 720aattaagaaa cgtaagaata tgtttgaggg atacatagga ggaagacgaa actatatgaa 780tcaaaacatt gatagaagta gaaatatctc taaatagatc gattgagagg aaaactaaac 840gagagacata taaaatcaaa gtaaaagagt agttattctt gattcaactc aaacctgtaa 900caaatcatat aaaattctat agatc 925941753DNAArtificial Sequencesequence of STAR A10 94gatctgaatg agatgtgttg gcgaacgcat atagtttttg tttcttgctg ttcataactt 60tgcttatgga attttattta tgtctttctc tatacctctt tggaccagtg ttccatttgc 120aatagagagt cactcgtgaa aaaaacaaat aatgtgtgtg tatcaattat tccctctcgg 180ccttatattt tgtcttcttt ttgctaatta tatactattg atttagatat ttacttatat 240tcatgacgtc ttcttcttat attcttattt aatttgaagt tagaaaatta acgttacaac 300ttacaactat taaattattg ttaattggtt ttataataag tatcgctctt gtctccattc 360acttgtcttt tattgtcccc agtaccaaac taccaaatac aattcatatt cactaattaa 420ttagtttgat gcaaaggatg atgcaatgtt aagaaaattg aaactctacc acattctaaa 480atgaagcaac tctaccatat ttaatttctt tagacttgga atagtcacaa tatgaatgct 540taggtagtta cggttagtta ggagtatcac acagaattga aaataccaaa ccacaatttt 600aatcaggtga ttcggtacta atttttatta atgaataaaa acataaccga accaactcaa 660agcagatatt aacctgaaaa tgaactcacc aaaacaataa tagaaagact caaatcgagc 720cggaaaccag attgagcaac gaactcatgg gaatatcata tctatttatg tccagactat 780taatatacat acctatgaca aaatactatg catgcaatgc aagactgaag taaccatatt 840tttttgggta aaccattgat aagctaaact tgaatatcca tagtacttca tcgtactatg 900tatcaatagt atagtaagtt tgacacaatt acattcagtt tgatttttat catataaacc 960tcccaacaat atttaaaacc gtatctatat ataaatttat ttgattaaat cagcctagaa 1020gtttatagtt cagtgcagat aaattcaaat tttgatatat atcttaattg aattaaccgt 1080cttttggtta aattattgtt acaagcttac aaaatccact atacaccaag ttggacttag 1140atatcatata tgagattaac agccgattac acttgtacat tgacctgacc tatacaaacg 1200actacaactt tatgtatata tatttctcta tttttggaaa ctcgtttgat ttgttttcac 1260atgtcgtgaa atttacagct ttgtttccta ctctcaaaaa tagagcatag agctggctga 1320tcacacttca aattaaaacc aacaacgtat ataaactata acccatgtga acacaaaaat 1380ttagaccttt tttcaaaacc attccaattt ctaacaaaaa caaaattaga aatcctaaaa 1440tctgcaaggt gtatggaagg caaaaaaggc taacaggatt aaaaacagtt tacattagtt 1500attctcttta aaatagaaag aagattttcg ataaaaacgt cgtcgtatct tcgtcgacgt 1560ctccgtcttt aatgggggag caaagggcaa gcggtgcttc ctcctccacc gactcatatt 1620caactccttc gccgtctgcg tcaccgtctc catctccggc tccacgtcaa catgtcacgt 1680tactcgaacc atctcatcaa cacaagaaga aaagcaaaaa agtcttccga gtttttcgtt 1740cggttttccg atc 1753951908DNAArtificial Sequencesequence of STAR A11 95gatctcactc aagctcatgc tcacgttcaa ggactttcca accgcaaggt tatcttcaac 60ttgtactcat taaggcctct caatattcat gtgttatgtt catgtagatg tccggtccag 120ttcaacaact gtttcattgc tttagttgtc acgagaaata tttgtatata ttattatggt 180gtgcaaaaca tagtaaaatg ttgttcaatt ggcagatgat gatgatgaaa atggaaagtg 240aatgggttgg agcaaatgga gaagcagaga aggcaaagac gaagggttta ggactacatg 300aagagttaag gactgttcct tcgggacctg acccgttgca ccatcatgtg aacccaccaa 360gacagccaag aaacaacttt cagctccctt gacctaatct cttgttgctt taaattattt 420catattgtaa attactttct gctttatcgg ttttaccatt tcgggagtct tttttgtgtg 480caatctgttt cgtttggtaa gcttgtagtt tcatgaaagt gaatgtaaga tatgcattac 540gtttgttgct gaagtgaatg taagatacgc actattatat ctcatgattt tctaagaaaa 600ccctcttaaa acgaagatgt ctatagcatt acgtttctat ttccatataa tacgttaaaa 660tttatggttt ttacgtataa aatgcaaaat aaagacacaa gtatatctcc aaagcaatgt 720accgttggga aaatttatta gtacgttttc aattgtcaat gcaaataatt aatggatgtg 780atagtcacaa ttaaacatac aataataaaa atgatgatga tgattcgatg atgtggtggg 840aaggataaat taaaccgact ttggggcagt gacaggcagt gtcagtgtca aagacaacca 900tttgtagtca ctatttctat cgaaggttgc aaattgaatg gtggaggagt atcaaaacga 960cacacatact tgaaaagata ttttaataat ataaaaaaat tggtgatggc gtaataacaa 1020acctagagct aattattatc cttaatgata ccaaatctat atgatacgat atttgtttta 1080aaaagagtaa agactgacac ttgagatgtg acactggcga tttcgctcac gtcaccactt 1140ttcccacctc aaataacgct tacggcttta tccattaatt ctaagtataa ttttaagtgt 1200attttttctt gccaaattca aatatatctt actaaatgga tgaacattat aaaattgtta 1260tcaaaaccat taaatgttct tataatttct ttcgttcctc caatgtcatc ccaagacttt 1320ttgacctaat atatgatata tctaacttgc tttggaatcg tatgacatat atcttcaaat 1380acatatttcg tatttttttt tcacgaaaac taatttagaa agtagaaaac cagctatttt 1440aaagaaaata aagtgtgttt atatatattc taaaacaatg ctataagaac ataagaccaa 1500gatatataca atgttatttt atatttatta ttaagcatta acattgaaat taaaaatatt 1560aaacatgtat accaaagtaa tcaacattgt agttattact actctctctg ttcatttttg 1620tttgattgtt tagaaaaaac acacatatta agaaaacata ttaaatattg attataaatg 1680tattattttt aatgttttac agttttctat aactttaaac caatgataat taactatttt 1740tttaaaaaat taccattcac ctatactaac caataaagat tacatagaaa actaaaaaaa 1800ttaatctttt aaaaacaaat tttttttcta aacaatcaaa caaaaaggaa cagaggggga 1860atattatttt aatttaattt agattaccat tgtagttagt aattgatc 1908961403DNAArtificial Sequencesequence of STAR A12 96gatctattgc tgtttatggc aggctgtcat ttcagaaaag aatggtggtt tgggatgtaa 60tgttggtgaa gatggtggtc ttgctccaga tatctcgagg tacatatatt tttcctctct 120gatgctaatc tgcttgcatc tgtagattgt cgaaactgag aaaaccatgt tatggtttga 180tggcttagtg cctaatatgt gtaattgcaa ctgtatgcag cctcaaggaa ggtttggagc 240ttgtaaaaga agctatcaac cgaacagggt acaatgataa gataaagata gccattgata 300ttgccgccac taatttttgt ttaggtaatt ttctgcttcc tggctaactg attttttgcg 360gcttcttgta gtcatggata gtcttggttt ggttctcggc attgtcattc acaattggct 420agtgagacga ataagatgtt aaatcatcaa atgtgtagcc tatcaatatc ttgctcttgc 480aagtttcaac tatgttatac gtttttgtgt attatttctt accttgtgga actgttcttt 540cctgaacagg taccaagtat gatttagata tcaagtctcc aaataaatct gggcaaaatt 600tcaagtcagc ggaagatatg atagatatgt acaaagaaat ttgtaatggt atgtctggct 660cgtctgaaca atattttttg tgtctatctt agtactcttg cagtattgta acgaccagat 720tctctgtttg gtctccttgt gggtttagat tatccaattg tgtctataga agaccctttt 780gacaaggagg actgggaaca caccaagtat ttttcgagtc ttggaatatg tcaggtccaa 840ctcggttccc ctactattaa cggttcacat agattttgtg ttctttcaga tcacactgtc 900ttctgattct tttctcagag tcaaatatct aaagagagag acccttaaat cttcttgtac 960aatcattttc cttgtctaaa ttctcagtgt taaactcttg taggtggtag gtgacgattt 1020gttgatgtca aattcaaaac gagttgagcg tgccatacag gagtcttctt gtaatgctct 1080tcttctcaag gtatttcgtc cgtcctattt tgtttattac tatgtattac ctgtgcacat 1140attgtatgtt tactgcctaa gaacgacaaa gacataatgt gcatacggtg atacaggtga 1200atcagattgg tacagtaaca gaagccattg aagtagtgaa aatggcaagg gatgcccagt 1260ggggtgtggt gacatctcat agatgtggag aaacagagga ctctttcatc tctgacttat 1320ctgtgggtct cgcaacaggt gtgattaaag ctggtgctcc ttgcagagga gaacgtacta 1380tgaagtataa ccaggtctgg atc 1403971140DNAArtificial Sequencesequence of STAR A13 97gatccatttc atatacatat taccaatttt ggcttttata ggtttgtatc cagaaggcct 60tttcgtggct acgattaagg aaaatacgaa aacaaaagtg aattttacta cttttgtagc 120atggtttatt ctactttata tacctaagaa atatgagcaa caattacttc tgtaatgact 180ttttactact tcgtagttgg tacaaactac aaaagattgt gttgttttta catgatactt 240tataatatct atattaatat atttagtcgt gtttaatcaa aaaagcacca gtggtctagt 300ggtagaatag taccctgcca cggtacagac ccgggttcga ttcccggctg gtgcattgag 360ctatgatgat ataggcttca gcattggttg ggtccattgc attcttctga actatcagtt 420gatgtatgcc acacctctga gctcttcttt ttttttcctc gtcaattaat tttttaaagt 480tttgtctgcc taaaaacttt cttctttttg attaatcata ttaagcatct cggctataaa 540aaccacggtc tactaactta acatgcattg gactagtttt agtggagagt gttcgagtta 600aaatgagaag ctcacgattg cataacggaa catttgattc gctaggcatc tccatttgta 660aaagtagcca ctccaataca aaatggtcga tgatggtgag tgggtgagac aaacccacca 720ccacctcaag aagatatatt tctctggtta agaatttgaa tggttgacaa agaaacggtc 780actctatata cttagaaaat atagtcatac atagacacca tcggtctagt tataataata 840accactggat taatgcccag tgaaaataat tgagtagcca aaacatgaat ataacaatat 900cccaatttac atacaacaac acaaaggagg ttttacacga ttctatagta caaactcata 960acaacaaaaa atcacacttt tgtttaacag ttgcctttat ggctttacta cagtatcttg 1020tccagggttt tcacacataa caatcacagt aaatcgtttc cttttctttg catcttccat 1080tccttttgta cacgtaacat ctccggcttc ccgaccatca gctaagaacc agatgcgatc 1140982125DNAArtificial Sequencesequence of STAR A14 98gatccagcaa ctaagtctta tgctcaagtg tttgctcccc accatggatg ggctatacgg 60aaagctgttt ctcttgggat gtatgctctt cccacaaggg ctcacctact taatatgctc 120aaagaggatg gtgagttcat caactagtta atatgctcaa agtggatggt gtgtttgata 180aactagtagt ttaagtagtc agattagttt caaggtcttc acaggattag gtagatatca 240cggcaatatt tggcctgtat aagtcctggt atcataagag agaactcttt gagattcaca 300ttggttttaa gttcatttgg cagtaggata ttagattttg aattttccaa tactatctct 360gtttgagatt tcataaatcg agtttcttct tcattatgtt cgctgacgat attgtttttt 420tcatttattt atgaatgttg ttacagaggc ggcggctaag atacatatgc aaagctatgt 480caattcatcg gcaccattaa tcacgtatct tgataatcta ttcctctcca agcaactcgg 540tattgattgg tgaagagcct gaaaaaaagg cataactatt gttactcttt agacaaaata 600acctatgttc tcacatcaag ctatgtaatg tcataacaac agcgacgaaa tacattggaa 660taaattgagt atgtccttaa tctgtcgttt tatctcttct tttaataaac acagtttatc 720tcatagtaag cagaagaagc tttacacggg ttgtaggaac gtattaaacg gtttgtttca 780atttcactct ctttggtttt gaaattctag tataaaccaa agtagttggt gcttcaagtt 840gtgttactta ttcaacaaaa aaatatatta tttttaattt ttaattttcg taggtaagat 900tacatagtaa caaaatgtta aatttaacaa tgtaagatta ctatgtaaat gcatgggcac 960cagtaatcac gtatcttgat gatatatatc cctaatccaa gcgagtcggc atttattggt 1020gaagaatctc aagactcata gtcatcgcta gttaacaatc tttttcggac aaaagcgtct 1080tcgttaaaat tcggcattat taaccttttt gcccttttaa aatcagaaaa tttctgtttt 1140actggtattt ttctttgacg attcaatttt ttagttgtat tatatatatg aaagaagctt 1200aactctctct cacagcttga tatgtcagta tctaaaacaa gcaatacata atttaattaa 1260tttatcataa aatatttatg attaaaaagt aaagaagata aatattaaaa agctaaatgt 1320ctcttataat ttaaaaataa aaattaaaaa ggattgaaaa gtaaagaaga taaatataaa 1380gaaactatta gtatcttata aataaataaa taaactaaaa attgaaatat aattatttta 1440gttttgaatt aagaaaatat taaatataaa aaaaattaaa cataaagaaa ctatatatat 1500cttgtaatta aaaaattaaa aaaaaatgaa aaatgagaaa aaaaatataa actcttcatc 1560atataattaa tgaaatttaa aaacttattg cttttaattt tttgtacaat aattaaggaa 1620atttagaaat taattattaa ttttagaaga aaaatgttaa aatagtttaa tagttttgat 1680tcactaaata catgtgtaca tatatgatgg tatgaggatc aagaaagtgc cgtaaaatgt 1740aaaacttcca atgttcctta gtgaaaaatg ttaacttttc tgttgacaag acgtgtatat 1800aaacatcacc tataccggag aagaagaaga cacaaaacaa agttaaaaag aagaaatttt 1860tggtgcagtg aattcgaaga gcaatatgaa gaatattggt tacattatta tagccacctt 1920gcttgttggt ctcctcctca tcatggctct agtggcgagt ttctattggg ccaaacgaca 1980tgtcaaatgt tgtggcggag agggactgtc gtcaaaggat gtgttcaatt tacttataca 2040attggttgct tttattctgc tttgtggttt atttgcttat ttggtatttt tggtttagat 2100tagtaaccta aagccatagc agatc 2125991196DNAArtificial Sequencesequence of STAR A15 99gatcagcaat tacagttgga tggaaaaaga gagacgagaa tgtatctgct gctggtgact 60ttaaggtagg ctgagtacca aattgcattc tgactgttct tacctcgacc acctttctta 120ctttccctag ctctaatctt gctattacta gattgaatct ggtggactcg gagcatcagc 180tcgttatact cgtaaacttt catccaaatc tcatggtcgc attgtgggta gaatcggaag 240gtatgtttta ttgacaatcc cgagcaacct aatgtatgat gtgcgagagg atagaaatca 300ttttttaagt tgtctttaca tgtgtggcgc aatcattgtt ctcattttac tttggaattt 360tttttttaac ttattcagca atgctcttga gattgagctc ggtggtggaa ggcaaatttc 420tgagttcagt acagtaagaa tgatgtatac agtaggactc aaggtaaact actctttaaa 480actttcggag ccatcttagc cattatgcaa tctgcttatt tccggtactc ttatactttg 540tttgtagggt attttctgga aagtagagct acaccgtggt agccaaaagc tgattgttcc 600cgtgagtgtt actttcttcc tttcttttct tgtggtgtca tgtctgctgt cttcggataa 660gaaccgaaca gattgtgtct taatctgtgg agtagaatat attaaaaaag cataaaccaa 720tagaaccaaa gaccaatcct aaaagcctag ggatggattc tagagcatta tccttgactc 780tctgaaacct ttacccaact caattatgga caaagacaaa catccgtatt actctgggga 840agtctttcac ttttgacacc ttcatgatga ttatctttga aacgtgcaga ttctactctc 900cgcacattta gctccagtat ttgcaactgg agcattcatt gttccaacat ctctttactt 960tttgttaaag gtgagtgatt ggaccctcta aatataatct acttttggtc tattgttata 1020agctgtttac cttattaaac attttcactg ttccacgcag aaatttgtgg tgaagccata 1080tttgcttaaa agagaaaaac aaaaggcctt ggagaatatg gagaaaactt ggggccaggt 1140gattgttact tccgagtttg gtagccaagc gagattcctt gtaattgtag atgatc 1196100692DNAArtificial Sequencesequence of STAR A16 100gatcgctttc agtctatcat gttttgagcc ttattttggg agcgatgtat taatattttg 60cctgttcttt attttttgtg ttgcagacat acaatgaagt gcagcggtgt tttctgactg 120ttggcttggt ttaccctgag gatttgttta catttcttct taacgtaagg acatcttttg 180ttttatgatt atggctctag ttattctttg tatatgtaac gcaaaacggt ggcaatacct 240agcactcata ttagactcaa gaactattcc ttgccacaca tctgtgtgat atttatatgg 300gctttttatc ttacatattt gaaatccctg tcttccttgt atactttcac cagaaatgca 360agttgaaaga agaccctttg acgtttggtg ctctttgcat cttgaaacat ctgcttccga 420ggtgtattct tttatccttc atcagtataa cttatcattc agagttaatt taccatccta 480acttaatgat gttgcattgt gttcgaaggt tgtttgaagc atggcactca aaacggcctc 540ttttggtgga tactgcaagt tctttgttag atgagcaaag tttagctgtt cgaaaagccc 600tttcagaggt actgagctgg cgtagatttt cttatttact actaaaatat gcatgcttta 660gcatagtgct tctactttaa tgacagttga tc 6921011826DNAArtificial Sequencesequence of STAR A17 101gatcacgata attttcctta attatctaat tctaagatag tctaaccatg aatattctta 60taatatctta actgtatagg agattctatt ttcatcccta aattatattc gtaattttat 120tcggatatac ttgcttttat tttcgtcaac agatatatat atatatatat atatatatta 180tttattttta attttcatta aaattagtga tttaattctc tattatttgt gtactatata 240aaacaaacaa atgaatctta taatgtttgc tttttcgtcc ataaatattt ccgggaaaaa 300tcgttagata taaatcgaac ctagtggtga gtgactcaca cacatgtgac aattcccaaa 360ataagtcccc cacgtacgct atgtctgttt tagtgtgcat gtagtaacta ttatttactg 420atttagaata taactagcat ttggccccta tttagggata acattgtttt agattatatc 480tgttacaact tttaactaaa aattttaaaa taaagcagac agtattaata tacaacaaat 540ttattatcat tgatcgaaga atatacaaag attaagaaaa agatataaag aaggtacaac 600ttttctaccc aatgaatcaa ttgcgatagg caataactaa caaatcaaga gtttagaaat 660ataagagagt ataagtacga aaattatgct gggtatatac atgtccgctt atttcatcat 720tagctccaac caattgtaat gtgttcttct tctcatcatc agtaattcag tttacaaaca 780ttcgttgaca cccaaagctt ggaagtctaa aaaaaaatgt aaaatgtgca caaataagta 840actacatgac gcagacgctg cctttgaaac aatatcaaag atattgcaga tataaagaag 900taaaataaga gatgacttta aaattgaagt atttgtatta atacaaaaat cttgcgtgaa 960aatacaattg cagtttaata caaaaaagaa attgcagata taaagaagta aaataagaga 1020tgaaagaaga atagtaaaaa gtatgagaat taatttacca tcaaaaaaac acttgagctt 1080cgattaagat attaaactca cccttgtttt aaggcaactg ttcagatgag aagccaaaat 1140ttgtcgttgt tccttgagtg tttgtgagac gggagaatca taggcattga ttgtattaaa 1200gaataatcct atggaaaaat ggagatgtat gagagaaatc gaattcagtc aaataaagca 1260gaaacaaagc aaaaaaaaaa aaaaaccata gaaatctaga agaaggatat atgattttcg 1320gatctatgga aaatttctat atatataaaa caaaattaca aacagaaata gaagatggta 1380aattggttca ttgagatgaa caaagtacct gatttctgag taatcgatta atgatgttga 1440gaaacccatt tttgagattt tacacagtag tcatggagtt tttggaagag agaaagtgga 1500gatgtggaga tcgtggggat gaaagagaaa atcatttgag aaagaaacaa agttaaataa 1560aaacgacaca tactatgcgt aaaaatgaaa aaataaaaaa tagtactaag ctgatgtgtc 1620aatcactgaa tgcattagtt attggaaaag tgactgctga tttagtatat ttagattaga 1680gaaaataaat acttgtaatc atttttctta ttagcaatgt tgaagtgaaa aaaaaaagaa 1740gaaaaaagtg tatatttatc atactcatag tgggaaattg ataattcaaa attgctgata 1800aacgttatga aagaaggtgg aggatc 18261021590DNAArtificial Sequencesequence of STAR A18 102gatctgttga ttggttaaat cgacgatctc aacggcggag gaagtgacga tgaaggcgcg 60gcagagagga caattagagt gagatttcaa ccaagtatca atacaaggaa cgtgaaacgc 120gtggttgcat ttaggtaaca atctcaagct ctcgttctct tgaaactcgc ttaaacaaac 180agagcaatct gaagattcaa caaatccatc catctttctg tatttgtaaa cagttatcga 240tttaatcaga gattcatcga gtccatcgcc accaccacca ccaatcgttt gattcggatt 300cgtagctccg ttgttgttgt tgttgttggt tccttgccag gtgtaatctg atgagattct 360gtttatagct gcggcggagg tagaggagga gttgtggcga cggcggtggc agtatttgga 420gatgagagtg tagtagctga cgaggatgaa ggcgctagcg aggattccga tgagagcgat 480gaggagagga gagaaatcag aggaggaaga gtcgtcttcg tcgtcgagat agaaggaagg 540aggaggaggg aagatgacgt aacaccattg agggcaatag acactgcata ctccttgaga 600acagtctctg tatgaatcgt atgttgtacc ccatggatta gggtttcctg ttgaacccat 660tatttgattg ttggagaaag atagagagag agagcaagga agaagatgga ggtgtcaagt 720gtctctctcc tttttctttg ggctctgctt ttgtctggta agtgtctatt tttttatttc 780gagttaattg gtattattag aggagataat gaataaatat atatgttcat gaaagctttt 840gcatgatggt gttaatacta attgaatgat gtttatagtg aatgttctac tttatcaaat 900ttttatttct agtatgaata aaggtgtaga atttgcttta ttcattttta ttctttagct 960ttctctttat gcttccattt tttttaaaga taaattaata cattagtaaa ataaatggag 1020ttcatttttt ttttttttga ttttattttg agaaatgaga acgtaacata agaagtgttt 1080tagtgttgac gaaataaaaa gagagagagg gtttagtcta tttcaaggca taaaaaaatg 1140gttggtgaag tgttgacgaa ggtggaatac tataacatgg gccacgtgga tgacaaattt 1200actcctcgac gtatctatta aagttgtggt cagaaataca gtacaattta ccgactacct 1260acatggaaga agaatatttt catttcattt caactacagt agtataacat tcacgttata 1320cgatttttca tttttgtttt gtaatcaaag taatgatttt ccaaaaaaat cattgctatg 1380attcgaatac atacagtttt atattagttt acatatttat gacaactata atacaaaatt 1440ttaatagttg ttcaagggac gattgatgtg aactcgccaa ccatatgccc tacgtacaaa 1500ataacatatt tacatgtaga agttgaaaat aataataata aagtgtgatt aaaaacaatt 1560atacaaatgc taacaatagg ctacgagatc 1590103706DNAArtificial Sequencesequence of STAR A19 103gatcttgatg tgtgttttgt gtttttgtta ttgcaggatg tatgtttcat agtgagacag 60ggcttaagag

ctttgaccat ccgactaata tgatgaaggc aatgccgagg attgatagtg 120aaggtgttct ttgtggagct agtttcaaag ttgatgcttg ttctaagatc aatagtatcc 180ctagaagagg aagtgaagct aactgggcgc tggctaattc tcgttgattt tgcttctagt 240ttcgttaact cttgcttctt tgttgcgttt tctttttatg tactcttgtt tatgtaaata 300tagccttatg aagacgataa agaaataaaa ttgatttgct tcttcgtgac atagcagtct 360ttacttagac aactgtgtga taaattcgca atctcactct ttgatagata agagggaggg 420aagaaagcag tggtaaagac aaaactgtgt tgattttgtg aatttagaag tttacaatag 480caaaaaagaa actttggtcg acttttatca ttcatcgttc cacatgtctg taaattcatc 540aggctccaat gggtttgaga gttcatgcat ctttcttctt gtttttgcct ttattttctt 600agcaaatttc ccagctttat ttcttttctc caaagctcga atctaaaagg caggaaattg 660gaatatatga gaactctgac agataatcat atatagcaat gtgatc 7061042064DNAArtificial Sequencesequence of STAR A20 104atcgtttcaa agcatggtct aatgatgatc ctgatctccg actgatccaa taacggttaa 60gcaacgctgt ttttgatcct ccattgttgt ttgccatcga tcaacactca gaaataaggt 120aattaacgca tctcgagact cattgtttta acaatctttg ttttgtttct tccaaattat 180tctcgtgaat atccgtaatc tctccgtctt ttaatgaaca acacatatca tatgcttttg 240tttgttttgt tttgtttttt caacatttca ataattttgt ctttttttct tcgatttaat 300ttgtttattt cctgctataa taaacgaaaa ctataattcc atgtaatgtt cgttgttgtt 360catagtgatt tatcataacg agcaacaaca taaaaatcaa gagaataaga aattagagtt 420atgctgctta tttgaattag acaaaaccta cttttacttg ttaaggaaat gaaaagatgt 480taataaagat gagcacatcg tacgtggcgc acgtggaagc acttctgtac gacggaccca 540gtccaactcg aaccccacac acatagcaaa ggttgttaag ttggctcgta ggtgaattta 600atacctgtta tttcctttat agctggctaa ttacctaaat tcgatccata ataacacatt 660cctactatgc caacatttaa ccctagtcaa actaattaaa acgtttctta ctttttggcc 720tattaaaacg tttcattatg ttccgcaaat agtatgaaat atataaagat tttctaacaa 780aaaattacta agaacagtta gactgattga gattgttttt atttcctttt atttaatttt 840cttttattat actctgttta tttgtgttta ataattagga ttctatttgt cttgtcttgt 900ttgctatagt tggagttttg ttcataaaga atggcgttta atacggctat ggcgtctaca 960tctccagcgg cggcaaatga cgttttaaga gaacatattg gcctccgtag atcgttgtcc 1020ggtcaagatc tcgtcttaaa aggcggtggt atacggagat cgagttccga caatcacttg 1080tgttgtcgct ccggtaataa taataatcgc attcttgctg tgtctgttcg tccggggatg 1140aaaacgagtc gatctgtggg agtgttctcg tttcagatat cgagttctat aatcccaagt 1200ccgataaaaa cgttgctatt tgaaacggac acgtctcaag acgagcaaga gagcgatgag 1260attgagattg agacagagcc aaatctagat ggagccaaga aggcaaattg ggtcgagagg 1320ctgcttgaga taaggagaca gtggaagaga gagcaaaaaa cagagagtgg aaacagtgac 1380gttgcagagg aaagtgttga cgttacgtgt ggttgtgaag aagaagaagg ttgcattgcg 1440aattacggat ctgtaaatgg tgattgggga cgagaatcgt tctctagatt gcttgtgaag 1500gtttcttggt ctgaggctaa aaagctttct cagttagctt atttgtgtaa cttggcttac 1560acgatacctg agatcaaggg tgaggatttg agaagaaact atgggttaaa gtttgtgaca 1620tcttcattgg aaaagaaagc taaagcagcg atacttagag agaaactaga gcaagatcca 1680acacatgtcc ctgttattac atccccggat ttagaatccg agaagcagtc tcaacgatca 1740gcttcatctt ctgcttctgc ttacaagatt gctgcttcag ctgcgtctta cattcactct 1800tgcaaagagt atgatctttc agaaccaatt tataaatcag ctgctgctgc tcaggctgca 1860gcgtctacca tgaccgcggt ggttgctgcg ggtgaggagg agaagctaga agcggcaagg 1920gagttacagt cgctacaatc atctccttgt gagtggtttg tttgtgatga tccaaacaca 1980tacactaggt gctttgtgat tcaggtaata tgtgttcaaa gttactactt tcaagcaaat 2040cctctgtttc ctcacatcat gatc 20641051834DNAArtificial Sequencesequence of STAR A21 105gatcttcttc tatatatacc ggtataagtc aactggcggc tgaacaaagg tcgtgaggta 60acaaaatatg agacaaatct acaggtcaga ttgggttctg aattctgata aggtcttaaa 120aaggagctca ccaacccaca aaaccatgga ttgaacaagt acaggtcatt gccttcattt 180tattctttac ttttctaagg ctcaagcttc ctttattgcc tttaataaca atatactaat 240gagtattttg cactcagtaa caaaattcag gagagtaatt ttttgcccta acatgttact 300tttatgtgtt aagagtttag aattttggat ctatgatttt agtttttgtt agggaatcat 360attcatataa ataaaatatt gccattgact taattgttgt tattcaccta atttctctcc 420aaatttggtc atttacctca gttgattcta tattatactt gctaagtgtt ctttgtctaa 480ttctctatca ttgtttgatt taataataac caaaccttaa gacttggaag caaagaagag 540agaaaatccc aattaatttt taataattca aagagagata ttgagtgact tccactaata 600caaagaaagc ttggtttgtg caatattttg cggttaagct attaattgct gaggcaacac 660cttttcacac tttgctttcc ttcttccaag ttttcaactt ttctttctta ctctttctat 720taatcaaact gcaacacaaa aatcatttgg ataatacatg tttagaagat gattaagctt 780tagttttatt tcaagattat cataattgtt atctgttgtt acctacattc atataatctt 840atcaaaaacg ataaagacaa aaaggggata caatataggt ttttattata aagaaacagg 900aaagaaagaa aagggttttc accaaacgaa attagttcaa tcatttaaat tatctttatc 960cttatgatta gtgtctttat atctgtcata tgctgcttct ccttccaact tcctttggat 1020tatattctct tctctttatt ttaatttcca tttgtggtag ctgttttatt ttttgtattt 1080tcacgccgtg tccctttaaa ataatattaa ctacaccact aatgttggaa catgaaaaac 1140atgaatgagg taattatgat gatgaaccaa atgttaagga caagctcggt gtaactaaga 1200agataattag tgaaacagaa caagtcaata acttgtaagc atttcagaat tgaaaataaa 1260gataagggag gatgaatatg aatttagtaa atgggtaatg aaagtgaaag aagaagaggg 1320aagggttggt tactgtctca agggtttgaa atggagacgg ttgcttgaga atgaggaaaa 1380agagttagta agtttttaac tctctctttc tctctccctc tctctttttc aacgtcaatt 1440cctttaagga atggcctctc tctctctctg aaagtgtgtg tgtatatatt aaacgactcc 1500atttctcctc tgcttagacc aaaactcatc ttctatactg caacaaagaa ggaggagccg 1560ttgagactac aaaatgactg cagcagaaaa cccttttgta tctgacacct cttctctgca 1620aagccagctt aaaggttctt atttttcttt ctgtttattg ttcatcaacc cttatgagta 1680atttgcttga tgttgaggtt gttctgcttt cttttaattc cactctgcag aaaaagagaa 1740agagcttttg gctgctaaag ctgaagttga ggctttgaga acaaatgaag agctcaaaga 1800cagagtcttt aaggaggtaa catgcatgat gatc 1834106751DNAArtificial Sequencesequence of STAR A22 106gatccattaa gaagcagccg caaaatcgga ttgagaacag gaaaagaggc ggttaaggct 60tatgatgaag tcgttgatgg gatggttgaa aaccattgtg cccttagcta ttgttcaact 120aaggagcact cggagactcg tggtttgcgt gggagtgaag aaacttggtt cgatttaaga 180aagagacgaa ggagtaatga agattctatg tgtcaagaag ttgaaatgca gaagacggtt 240actggagaag agacagtatg tgatgtgttt ggtttgtttg agtttgagga tttgggaagt 300gattatttgg agacgttatt atcttctttt tgacagaaat acattgaaaa ctaccgttgc 360taatttgata ggtatacata tatagacatg tatatattgt ataattatat gtcaagatta 420tttatttatt ttacattttt cacaaaaaaa aacgttaatc tatttttctg tcacaagtgt 480gtttttattc atactacata ctacaacgcc aatttaacat gccaaatata aaacatacat 540gggcaaaggc ccaacagcca gtttaaagaa ctttgtctga agagaaagtt gttgtatata 600tcacaaggga tatgtggtaa ttgggaaaca tgttgggttg acacgtggga aattgaagga 660gatggagttt ccgtcactgg tagaatcttc taacactaga gagcttcaat tcaggttgaa 720atcgtcagaa aactaatgca gacggtagat c 751107653DNAArtificial Sequencesequence of STAR A23 107gatcaaaact tagtcaaatc gttccttcca ttttctttca gtttgattcc actttaatgg 60cgtcataatc atctcttaaa tcaaacaatg actccactat ctcgtttccg atctcttgtt 120acataaagtt ttctgtagca ttgagattgt ccttttcgga attgctttta tttgcgcagc 180ttgatggaaa caacaaacag tgtagtagtt tagtagaaag actgagagat aaaacgaaga 240gtcaagttcc taagtccatt acttgcatta accgcttaga gatatcgcgt atagcaccat 300tacacgcaac gatgaatagc ccgaaaggat ttggacctcc tcctaagaaa accaagaagt 360cgaaaaagcc aaaacccgga aaccaaagtg atgaagacga cgacgatgaa gacgaagatg 420atgatgatga agaagatgaa cgtgagagag gtgtaattcc agagatagtg accaacagaa 480tgataagcag aatgggattt acagtggggt taccactctt cattggtctt ttgttcttcc 540cattctttta ctatctcaaa gtgggattga aagttgatgt gcctacatgg gttccgttta 600ttgtttcgtt cgtcttcttt ggtacggctt tagctggtgt gagctatggg atc 653108548DNAArtificial Sequencesequence of STAR A24 108gatcagactg aactcgtgta ctctgagcct tgcttcttgt agctctttta gctttcacat 60tttcatcagt attcacatca ttcctgataa ttgtgccaga agtcccacga ctatcttgtt 120gctcactaat ggttgctgct gcagatgatt ccatgttgtc ctcttgtgaa accccaatgc 180ttcgtctagc aactgtattt cttgcacttc ctgctttgcg gtttttacat ttggatgatg 240caactttaac tttaggtagc ttcttttgag taagatcaat ctcatctcta cctaggacct 300gcaaatcgat gaaatttgag ttcatttcaa cacacttgat gacactatca tagaaaacaa 360aaagaccttg ctgtaccaga gtgaagaaca gcctttacct tggccttcac aggactaggt 420agaatctccg gagaacaagg cctctgagtc cattcaaaca tttcgctatc aaacatgtca 480cctggattgg gcttttgttg ctcgtcttcc tgaaacattc atcggaaaaa aagtaagatc 540aaaggatc 5481091000DNAArtificial Sequencesequence of STAR A25 109gatccaaact ctgcaatgta tattacgaag tcgtttgata taacacctct cttgataaaa 60gatgattaga acctaaagta attttaaaat atggtgaaaa attagactct tggagtatat 120aaatggctca atctgtattg cccgcaccgc ccaaactccc atggcaaatc cattgacgaa 180accaaggtaa aaatcacatg ctttgagcgt ttttttaaaa cagaagtgta agcttaaatt 240ttttagttta atagtagtaa caaattcaac cttgtgaaga gatttattaa taatattaaa 300atcattcccc taattatttg ccttgagttt cgagccttct actgtaccac tcacacatta 360aaaatcatca gactattcaa actttcttac atggttgatt agttcatctc atatatgctc 420agtatcatac tcttgcagat taatttttca ttttaattat caacgaattt tttatttaat 480tattcatgac caaaatacat ttattttttt taaataaaac aaataataaa tttggaagtc 540aaaaatacaa tcaatagaaa aaaaagtatg acagtgatag ataatatttg cagaatatta 600tgtgaaagct attttctctg taacaataaa tgagaaaatc tttattattt tacatgaaag 660aaaaagaaaa caaaacagag atatttttcc agctgaaaag aacaaacatc tctcattgat 720gttcagtgaa cttgcaccaa acttcacttc ttctatactt cttcatagcc acaaactcag 780ttctttgcaa gaaacacaaa cttaagtatt caaaatatcg tcatcatgtt ctcaagattc 840catgctctgt ttcttctcct tgttctttca gtaagaacat ataaatgtgt atcttcatct 900tcttcttctt cttcttcttt ctcattctct tcattttctt cttcgtcttc ttctcaaact 960cttgtcttgc ctctaaagac ccgaataacc ccaacggatc 10001101926DNAArtificial Sequencesequence of STAR A26 110gatcctcgat tcttatctgg atacagaaga aaacaccttt ttgtctttta agtactcgga 60gaaatctgag ggtatctttt tcttgagcag atggaggtga agtcctgagt tggggaggag 120ggggctctgg aagacttggc cacggtcacc agtccagtct ttttggcatc ttaagaagta 180acaggtttgt tttacttaat ttcaatatcg ttttgtctct ttctcatgca ttttttgctc 240acaagaattt tcccatttcc tcctttactt tatcatgatt ccttcataat tttcttgtat 300tgcactgtaa agtatccccc tgattgcagt gagtttactc caaggcttat caaggaactt 360gaggggatca aggtaatcta gtggtgaaga atatccacct tggatgaaga gtttctagtt 420acctagtggt ggttttaatc tttagacttt catgcttatg tttttccatt ctttctgtcg 480agcactaggt cacaaatgtt gctgctggtc tgctgcattc agcatgcact gatggtattg 540atttactttc ttaaaagtat gaatgttgtg ccatttaccg aactttatga ggtttgtttg 600caaatgcaga gaatggctct gctttcatgt tcggagagaa atctataaac aagatggtaa 660gaaaatgtct ttttctttga tttctgtggt catatatgtg aagctatctg atgggaaaat 720acagggcttt ggaggagtaa gaaatgccac aacaccatcg attatcagtg aagtaccata 780tgcagaagaa gttgcatgtg gtggctacca cacatgtgta gttacaagta atactctctt 840attatatcgt tctttctttg atattgagtt tgcttgtata ctgcaaatgc ctgtcctgct 900caaatttctt tttgttattc tttatagagg cccaaaactg ctctttagtt tctgctaaat 960ttatgaacat attgtgtttg taagatggtc gataacaact catcgtttga tgtttccttc 1020gtttttggaa ggaggtgggg agctttacac ctggggctca aacgaaaatg ggtgccttgg 1080aacagagtaa gttacatacc ccgaaaaaat agaatgtttc cccataagat gaaaacaagg 1140ttcttgaact gtacctatac tcttatttca aaaaattcag ttcaacgtat gtctcacact 1200cccctgtgag agttgaaggt cctttcttgg agtctactgt atctcaggta tcttgtgggt 1260ggaagcacac tgcagctatt tcaggtagca tctcttttga gtaaaacata tttgtttcct 1320ctctcattgt ataagttaat tcaactcaat ttctgaaact tgtttgcaga taacaatgtc 1380ttcacctggg gctggggagg atctcacggc acattctctg ttgatggaca ttcctctggt 1440ggacaattgg tttgtttcat catcttatct tattgatcaa atctctgaaa caacattttc 1500aagtgtcgaa gagaataaat atggtatgct taatatgtag ggccatggta gtgatgtaga 1560ctatgcaaga ccagcaatgg tggacttggg aaagaatgta agagcagtgc atatatcttg 1620tggcttcaat catacagcag cagttcttga acatttttga agactcggtc tcaagttaat 1680atcatataca gatgtttagt ttattcttgc ttaaacatct atagactaaa aaaataataa 1740gaaatttaca ctattgaata gcgatcaatt acaccattgg ttctaacttg aacaatttag 1800taaataggtg gaatattctt gtcgtgtaaa ttattgattt tatttattta tttttgaaaa 1860ctacaacaaa cgatagaaga gttgaggaaa tctctttgta atcataatta tgagaaaatt 1920aagatc 19261111109DNAArtificial Sequencesequence of STAR A27 111gatcggaatc attttgggag tttgaaggaa ctaaacataa tatgcatgtc gaagtcaact 60tattgcaaat aattttgaaa tgattctgaa ttggaaattc atgaagctta attattttat 120ctaaataagt ttaatatagg tttgagtgag atatcgagat taaatgataa gagtctttct 180tcgaggagac attagaattc tacacaaaaa tcgaaattaa tctagtcctt gacaatcagt 240tttcaattaa tcaaaaacct ataaaattca actcaaaacc aatcgtatga aacttcatta 300taccatataa tctggttact tagcttaaat ctctacccgg cgatgtttca tgcttgagag 360actaggtaca taggacacta ggagtactgc atatatggtt acctcatgag ttctcatcgt 420aaaatcatcc aataaaaaat ggtttcctgc ttaggtatac ggtataccat cttgtatcgt 480taaaatttat agctcagttc gttgctaaca gtcaaatacg tctttccagg gtaaaaaatg 540tggaaatttg ttccactgta aaaacctaat aatttttgac attaataatt aaaagggatt 600ataatgtaat atatacaaag ataggggaga cagagacgaa ggcccacaca tctttaacaa 660aagaacaaca agcccgtgac cccaaaataa aactagcttt cagatttatt atttttcatc 720tgacataatt gcaaccgtta gatttcattt ctcaggtccc attctgactc agatccaacc 780gtccatattc ctctagtgtc ttcaatagtt gggccccttt tctttttcct ctcgccgtac 840actctccttc cagcgccaac gccaccgccc gagccacttc ttccgccggc gccaccgcga 900tttcctcgcc ggaatcccct ccttcgccgc ctttcccgta gaccacggaa aggatgctta 960tggcgtattc tctccctcta ccagccaatc tcgccatcac cgctaccatc gccggcaccg 1020tcatcgcgtg agcgcgaacc tccgccgctc cttctgccgt tgtacacatt agctcaagag 1080cagctaaggc tcgctccacc gctgagatc 11091121659DNAArtificial Sequencesequence of STAR A28 112gatcgaactt tggtaacatg cttgcttact gctttctatt gtctgcaaaa cctctgttct 60gggtgacctt ctggcccctc tctctcgaag cttcagaact atggaggaga gattggataa 120aggagacaaa aggtgtggtg tggcgaaatg ttagggtacc ggcaattgtg tatgtatgag 180ttgattttgt tcttttctca taaagaggat ttaacaaagg atgagaaaac aaatccaact 240tgagtactac gaggagataa aagcttttat tgggtattga gtattgacac gttgttgaaa 300gtctgataca ttttagactt ttactgcata tgtccaaata tttagatttt tttttcgttt 360ctcaaaaaag taacttgttt aacaaaaaaa aatcgttatt gggcttttcg tttcttttat 420attgggcctt gagccttttt agcttttgta tttttagtcc ttttcgggtt tatttattta 480ttaataagat accaaaaaca taacaaaaat gtagttttgt atttttaacc tagtctttta 540aatatttaaa cttaattaga aaaattctat ttaaaatatt ataaaaaaaa catgattttg 600tgattttccc atattttgtg taactatttt tgacaagctt ttgaaacaac aaagacaaaa 660tccatgtgat aaggtcggtc aaaaatcttg cgtagtagag gagttaaaga tttttggatg 720gttacaatgg tatactctta tttgatatcc catcaatggt atatagcttt gaatggtagg 780acaagtgaga gtaaaatttt ctcatcattg ctaagtttta ttttaggttc tacattgttt 840cacccttctt aagtatccta ctctcaacta gaaaaaaaaa ttgtgagggc ggttttatcg 900gctggaatgc agctcatgta gctcccacga cggagttttc tggctaagaa actcggacac 960aacgttggcc tccaatatct tcaaggcttc ttcattcgtc accgacctcg gtgtcttata 1020ctgactcaca gaagagcctc tagacagaaa gaagttcatg agcttgtcga aagcgccagg 1080cttaacaacc ttaatctcaa gtggtccaat gttcttatca ttctttcgtc cttttctgta 1140aaccgcgtcc agagactcct caatggtgaa gcagcattcc tccaaaacat tctggtcaag 1200ctcaagcttg gcgtccttga cttttctccc gagttcccag tagagcacgt agtgacctgg 1260atacgaggag gaatccacac ggctagtgaa atccatgagc attaggtcat gtggctcaag 1320caggagactc gcgttagtca ctgccttgag gaggtcttcg tcgtaggtct tgtccatgtc 1380gatgctcaga acaactttct gtcttcccac gaaatgaaac tgtggcgcat tgttgtagaa 1440accagtcact cttaaaacgt cccctaaacg gtacctatac aaacctgtat aaagaatttt 1500gatacacatt aagaaaatta ttaacatgtc atttagtttt gaaattgaga gagtaaacaa 1560gaaaaaacac ttaccagcaa acgttgtgac aacaggttca taatcatgac cgattttaac 1620atcgacaaga tcgactacaa caggattctc tgcgggatc 1659113874DNAArtificial Sequencesequence of STAR A29 113gatcagagtc acaaccatag gagtcggaga cggccatgca tgtgtcttga tagaagaatt 60aaccggttct aaatctgaaa acgaatccgg tcgtctcgaa ccgaaatcaa taaccggtcc 120ggtcaaagaa acggttgcac gagtgaagga aacggttacg aaaacggagc cgttaatatg 180cgatgacgga gtgacaaagg ggaagctgac gatgtgctac gaggtagacg ttgacgttga 240cggtgggagg tgtgttaacg gagatttaac ggcagttagc tacggaggag gtttgggtaa 300ttgtggcggg gattggtggg agaaatggga tggagtggtg aggatgagaa atggtgatga 360cagttggtac cgttacgtgg atttaacggt gattaatgga aatgtggtaa ggttatggga 420tgacaacaaa acactagtaa cggcggcatg tgtctaaatt agagaagttt catatttcgg 480aaagttttta aatcttgaga agctttcttg gtttgaagtg tttttttttt gttggttgat 540taagttgtaa tttgtaaata attttcacac aagagaccaa gaaggaacgc ttaaatcaat 600atcaattggt gttgattccc agctttttct agtcgaactt aggtaacacg tccattgcga 660tgatgaattc gtgacaaggg gtcaactatt tgaacacaac aaacaagtgc gttttcttgt 720taaggcccat ctaaaattga ctacacacat ttacttttag gcccatttta aacttgactg 780tagcctgtag gcatgtattt gttcgtgtta ctcccagcct caaacccgca aaatccacga 840attcttctta cttagtctag actctggtct gatc 8741142138DNAArtificial Sequencesequence of STAR A30 114gatctggcta atccgtttag cacacaacca gatgtaacat tggttgcaaa gattattgaa 60gagtctcgat ctaatgtaac acacctctgc gcattcagga gtgcttacgt caacacattc 120cgggaacgaa aaactgttag cgtatgtgta ttttaaagta ttaccatatt tctttatatc 180ttctagcacc tcctcacaaa tgtcacgtgc gtcctccgat tccaaagcat aatggttgct 240tccgaagagc cgaaggtaga caccacccat gtgagcatta ccagcacata tgtaaagaat 300tgcgcatgca agggttgcag cggcgttcct tggggcgatt cgctctaagt gtaggatagc 360tccctggatg tcagactcat gtgtaacgag acgcagtcct tcatggtaaa tagccgtggg 420gttaccagct tgtaagcacc gtttgaagaa gggtctatag cgaccttcgg agttgatgtc 480atttggatcg tggcctgccg cgtagaagtc atcgggatcg tcgcacatgc tgaaaatgtt 540tgcatttttg aggacatccg gacagtagac aatgtctctt ccacgaggac cggatttcaa 600cataggtccg aggtaccacc aacatttgtc agccattttc ttggctatct tcgcaagcaa 660atcgtcagga atatttgggt ttgtcatatt taggagtaag gtgtttcgag aaaatgaaat 720ttgaacactt aaataagcat cattgaagat atggttgggt aagttatggt tgtatttatt 780gcaaaggtat taagtgatga tgtgtattca tattgtcaaa tcaaagtaat agtattccat 840atataatttg ttatcgttgt tatgagcaac ctctttttat taacagctta aaactagacg 900tgtacgtttt actgacggtc ttagtgtacg tccacattta catttctaca tttactcaac 960aaacagtgta cgttgtagtg tatgttttag tgaacgtcca catttacatt tctacatttg 1020cccaacaaac

agtgtacgtt gtagtgtacg tccacattta catttctaca tttgcccaac 1080aaacagtgta cgttgtagtg tacgtttaag tgtacgtcca catttacatt tctacatttg 1140cccaacaaac agtgtacgtt gtagtgtacg ttttagtgta cgtccatatt tacatttcta 1200catttactca acagacagtg tacgctgtag tgtactatta gtgtacgtcc attcataaat 1260atcaccattt atgagacaaa ccaaagacct catacgtttg catgtgttat tttttagtgt 1320acgttagagt tgatatctca tgctagtgaa cgtccatatc tagttttccg agacaaagaa 1380aaaacctcta agtattattt ggtagatgca cgtgtacgga gttgtggacg cttagatttt 1440aatatccaaa tttacattta ctgcagtgtc taaatatcat atgtgaattt ggctgaaaaa 1500tattcaactt gagaaacata acacaccttg caaatttctt aagcaataat ataatttcaa 1560cataaacata aacaacatag tagaaggctt atcataattt gaaacatgac atagcggata 1620acataaacaa acatataaag tagaatggaa taactatagc atttgactaa cacgcctggc 1680acacgaccag aggtaacagc ggttgcaaac gttttggaaa gctcctgata ccatgtaaca 1740atataaggcg caaggaggca tactaattcc atggctggta ggataagaga acgtaggacc 1800atatgtattg ctgtatggag ggtcaaactt ctttatttcc tcgatgaact catcacccaa 1860aactcgagtg gcaaccgagt ccaatggata atggttgcgg gtgaagagct gtagaaacaa 1920gccgcccata taatcatacc cagcacatat gaatacaatg gcgcatgcaa gtgttgcatt 1980tgctcgtact ggagcatgac gctgtaagag cctgatggct ccattgatgt ttcgttcatg 2040cgttagaaca cgaatacctt cgtaatacac ggccgtggga ttattagctg caaaacacct 2100taagaaaaat gttcgatgtc ggccttcatc agcggatc 21381152092DNAArtificial Sequencesequence of STAR A31 115gatcaaaaga atcgtacttg aaatatttag tggaacgcat atgtcagagt tacagatatg 60gtttaactct ttttatctcc tttttttaat ggtgtttctc tttttatctc ctataatctt 120ttgggaattt tttattatta aatattaatt aaaaagataa attcttagag aaaatcccaa 180ctgacttgtt aactagtgag acatatctta tttattctct gcttatctaa aaagaaaatg 240aaaaagaaaa aaaaagtata tattagaaga ttaatataag tttaggggga aaatgattat 300tattactatt tataaaatta gtatatttca aaattgtaca attaattact aagccttaaa 360ataaaaatgt aaaagaagat tatcatcaag aatagtatac catctttgtt tcaaaagaaa 420agtttactaa aagaaaaaac ttttgtttaa tttctactaa agctgaaagg aaaatgattg 480tcaatttgtt attattatta tttatatgat agatttctta agaaacgtat agagttagtt 540acaaattcta aattaaaaat tgtatgataa gattatctta agaaagttat acaatatatt 600cctaattcta aaagaaaatg gttatttttt tggaatagat atacacaaca aaacaaattt 660agtataagaa gatatgttag attaactaaa taaacatctc aggcatgaaa ctggattagg 720ttaaccagag gtccagagac ctatatatct ctaggcatta gggtttaact acggagcaaa 780gcctcataat caagtttata tcttgcgcat ctttagcaac caatcaatta tctaagaagc 840catgactaat actaatgttg ctgctacaaa gcctctttct actatggtcg atgaatctcc 900tagccttctc cgtgattggt ggtgagactc tagatcaatg atttttctta cttttttccc 960attactatgt tatgttacgt aacataagat ggattaaact gaatctgatc ctcttaaatt 1020atattggttg cagtatgaac aagaacctac aatacaactt tgcgatgaac ttcgtcatga 1080taatcatcaa cattgaagca atcttgtcta tcagaaacca cgaaaatcac gtaaggaaag 1140attattcaac gattttgata atttccggta tgttcttgcc tttcgcctat taagttgcgt 1200ttgttgggtt ggcgcaatca gggatgtgac attatgtgaa ctcgcctaca tcttcggacg 1260catcagtcac aacataggct ttattttctt cctagaactc ctctattgta tttctcccta 1320cttggctcta ctcgttggtc tacatgtagg ccaatggtat ctaacttcca tgattggact 1380gtctctatgg gaaggaatgc aagcattacg aactgatatt taacctcgtt taatagtaaa 1440atctaaactt atttagctgc atattttggt ttaaggcaat cgagaatgtc ttagcatcta 1500aagcttactt cgtgggacgc atctgtcaca cgttcggctt ttgtattttc gtccacctcc 1560tctattcggt ttctcctcac ttggctctat acttcggtct cccttgtttg ctaggtttcg 1620tagccgtcat gattgcacca agttgtccgt atcaatggaa aggcctatgc aacaaagtgc 1680aagagttacg agactggtgg aagcatgtga atcgaccaca atcctcggtt gttattgttc 1740aaggatctcc atttctaaga tgtgaatttt aggactcttt tatccctttt gccttttaaa 1800ttggaatacc aacgtttatt atgtgggtta gttatgtgtg tatatgatat acaaatcaaa 1860caacatatat aaggagaaga gatattgaat gttgattctt aatttacagg aacatgaagc 1920tcgggtcttt ccggcaatgc catcaatatc cgaggcggtg cagtttcttc gtcagacgag 1980aaaccagaga gtctagtatc ctaattttga acaaatagag cataaaggaa caagttatat 2040agcttcacat aacccgaaac atgttttaag tttcaatatc aaagacaaga tc 20921161290DNAArtificial Sequencesequence of STAR A32 116gatctagaca tatgtgtgag acgtttcatt gtaggtatct gaatgtaaag ctcaaagctt 60taacctttga accgataaac ctctaaagct ctctcttttc cttggatgag tctcacaagt 120taagaacttc agtgaaataa tctgacttta ttgaacccaa acttgggtat cactgtttat 180cttagcatta cagagttttg tttttgttat gtacattgga tttgaagtct acaatgtttt 240tccaggttta taaaccggaa gaatatagcc gggttctagc tatctgtggt cctgggaaca 300atggtggtga tggtttggtg gcggcgaggc atttgcacca ctttggatat aaaccgttta 360tttgttatcc caaacgtaca gccaagccac tttatactgg actggtcact caggtttgtg 420taaccagtgc ttaatttatg ggggatcttt gttagctttc tccgtttctt tactgcctgc 480tgaatttgcc tgtttttgta gttggattca ctctcagtcc cttttgtttc cgttgaggat 540ctgccggatg acttgtcaaa ggactttgat gttattgtag atgcaatgtt tgggttttca 600ttccatggta actatttttg tgcatgaatc gttagaattc ttcaaagcat gaaacaatta 660taagaagtaa attcatcaaa cttttgaaca gcaagttttg gaatcaaagt ctcagagatg 720caccttattc atttgcatca tgtttcagtt ggcctttgaa aatccatttt ttgcacatgt 780aggagctccc aggcctcctt ttgatgacct catccggcga ttagtatcgt tacagaacta 840tgagcagact cttcaaaaac acccagtcat tgtctctgtg gatattccct ctggttggca 900cgttgaagaa ggagaccatg aagatggagg aattaagcct gatatgttgg taagtcttag 960ccgaaatgct tgtgtttctc tttttctctt gtactcattt gttactatct gatataatga 1020aaactacttt ataaattgaa catatttact ctttttaggt atctttgact gccccaaaat 1080tatgtgcaaa gagattccgt ggccctcatc actttttagg tgggagattt gtaccacctt 1140ctgttgcaga aaagtataag ctggagctcc ctagttaccc agggacatct atgtgtgtta 1200gaattggtaa acctcccaaa gttgacatat ctgctatgag agtgaactat gtctctccag 1260aattgcttga ggagcaggtt gaaactgatc 1290117869DNAArtificial Sequencesequence of STAR A33 117gatcccgttc atgtattttt gccagttcga gttggggttg gttctgttta ctttttctag 60tccatgtatt ttgcagacct attaaaacca ttctgttttt tttttggacc aacaaaaccc 120atccgttttt agatacgaaa ataaaatttt attaaaacca ttatttttct tggaccatca 180aaacccatcc gtttaaagat acgaaatgaa attcgattga taaatacaaa ataaagttca 240ccaaacttaa ataaaaaggc atagatggga ccaatgagaa agaaatttct tttctcctca 300atttccccaa aaatatataa accttaagtt tacttttttg ttgcaaggaa aaacattaat 360ctttttcaac tttctaaaaa caatcatttc aaacgttaaa ggaacctcct cctttcttta 420cgcgtttgca atataaccca agaagaccgc ttgtttgtac aactttccaa aaaccaaaca 480gtagtgtaat aaacctctga cttctttttt cttctctatt tttgtgggtg ataatcaatt 540cactcggttt gaaatttcgt ccacttttca aagatgagtg aatgaaaaag ccacgaaact 600ttccatttct tcctctgtgt ataactctca ctgagtacga cttgccattt tctcatccaa 660aaaaaatgtt tatccaaata catatttgtg aactttgctt ttaaaccact caagattctt 720ccccatggct tcttcgtctt cttcttctcg gtctcgcacc tggagatacc gcgtcttcac 780gaacttccat ggacctgacg tccgtaaaac attcctcagc catttacgta aacagtttag 840ctacaacggg atttcgatgt ttaatgatc 869118921DNAArtificial Sequencesequence of STAR A34 118gatccatgct tttgagttta agtgatttat ttaagatcct ctaaactttt ttttcttcac 60ttagtggtgg ttccagtcaa tttagcaagt aagatgttgt atgtgtcaat gctataactg 120tgaattttca gctattgtag tttgattttt gtctttgtta gcttcaggtg tcttgaatct 180gaatctgtgg ctatatttgg tgctcggtgg tgagcaggaa gggaggggga tattgtcagg 240gttttaatgt acgtcagatg aatagagcaa ctaatgttac tggcagtaga aggagggggt 300ttattctcag cgtccgcgtc tgggtatagt aagggattga cccttctttt ctctggtgat 360aaagacgtag ataggcccat gagagttgtc ccgtggaatc actaccaggt ggttgaccaa 420gagcctgagg ctgaccctgt tcttcagctg gattctatta agaaccgagt ttcccgcggt 480tgcgctgctt ccttcagttg ttttggtggc gcttccgcgg gacttgagac cccttctcct 540cttaaagttg aacctgtgca gcagcagcat cgtgaaatat catcaccaga gtctgttgtt 600gttgtttctg aaaagggtaa agaccaaata agtgaagctg ataatggcag cagcaaagaa 660gctttcaaac tctcgttgag gagtagcttg aagaggccct ctgttgcgga atcacgctct 720ctagaagata taaaagaata cgagacgttg agtgtggatg gtagcgatct cactggtgac 780atggcaaggc ggaaagttca gtggcctgat gcttgtggta gtgaactcac tcaagttaga 840gaatttgagc cgaggtacgt gtgatatgtt ttcctcttat tgagttgctt aaatcccaat 900acgagttaat ttaagtagat c 9211191140DNAArtificial Sequencesequence of STAR A35 119gatccatttc atatacatat taccaatttt ggcttttata ggtttgtatc cagaaggcct 60tttcgtggct acgattaagg aaaatacgaa aacaaaagtg aattttacta cttttgtagc 120atggtttatt ctactttata tacctaagaa atatgagcaa caattacttc tgtaatgact 180ttttactact tcgtagttgg tacaaactac aaaagattgt gttgttttta catgatactt 240tataatatct atattaatat atttagtcgt gtttaatcaa aaaagcacca gtggtctagt 300ggtagaatag taccctgcca cggtacagac ccgggttcga ttcccggctg gtgcattgag 360ctatgatgat ataggcttca gcattggttg ggtccattgc attcttctga actatcagtt 420gatgtatgcc acacctctga gctcttcttt ttttttcctc gtcaattaat tttttaaagt 480tttgtctgcc taaaaacttt cttctttttg attaatcata ttaagcatct cggctataaa 540aaccacggtc tactaactta acatgcattg gactagtttt agtggagagt gttcgagtta 600aaatgagaag ctcacgattg cataacggaa catttgattc gctaggcatc tccatttgta 660aaagtagcca ctccaataca aaatggtcga tgatggtgag tgggtgagac aaacccacca 720ccacctcaag aagatatatt tctctggtta agaatttgaa tggttgacaa agaaacggtc 780actctatata cttagaaaat atagtcatac atagacacca tcggtctagt tataataata 840accactggat taatgcccag tgaaaataat tgagtagcca aaacatgaat ataacaatat 900cccaatttac atacaacaac acaaaggagg ttttacacga ttctatagta caaactcata 960acaacaaaaa atcacacttt tgtttaacag ttgcctttat ggctttacta cagtatcttg 1020tccagggttt tcacacataa caatcacagt aaatcgtttc cttttctttg catcttccat 1080tccttttgta cacgtaacat ctccggcttc ccgaccatca gctaagaacc agatgcgatc 11401206DNAArtificial Sequencepalindromic DNA sequence 120canntg 61216DNAArtificial Sequenceoligonucleotide 121aaaaaa 61226DNAArtificial Sequenceoligonucleotide 122tttttt 61236DNAArtificial Sequencehexamer 123acgtga 612426DNAArtificial Sequenceoligonucleotide 124gtacggatat cagatcttta attaag 2612526DNAArtificial Sequenceoligonucleotide 125gtaccttaat taaagatctg atatcc 2612651DNAArtificial Sequenceprimer 126atcagatctg gcgcgccatt taaatcgtct cgcgcgtttc ggtgatgacg g 5112741DNAArtificial Sequenceprimer 127aggcggatcc gaatgtattt agaaaaataa acaaataggg g 4112836DNAArtificial Sequenceprimer 128gatcggatcc ttcgaaatgg ccaagttgac cagtgc 3612932DNAArtificial Sequenceprimer 129aggcgcggcc gcaattctca gtcctgctcc tc 3213031DNAArtificial Sequenceprimer 130gatcgaattc tcgcgacttc gcccaccatg c 3113147DNAArtificial Sequenceprimer 131aggcgaattc accggtgttt aaactcatgt ctgctcgaag cggccgg 4713231DNAArtificial Sequenceprimer 132gatcgaattc atggtgagca agggcgagga g 3113340DNAArtificial Sequenceprimer 133aggcacgcgt gttaacctac acattgatcc tagcagaagc 4013448DNAArtificial Sequenceoligonucleotide C65 134aacaagcttg atatcagatc tgctagcttg gtcgagctga tacttccc 4813554DNAArtificial Sequenceoligonucleotide C66 135aaactcgagc ggccgcgaat tcgtcgactt taccactccc tatcagtgat agag 5413639DNAArtificial Sequenceoligonucleotide C67 136aaaccgcggc atggaagacg ccaaaaacat aaagaaagg 3913732DNAArtificial Sequenceoligonucleotide C68 137tatggatcct agaattacac ggcgatcttt cc 3213833DNAArtificial Sequenceoligonucleotide C81 138aaaccatggc cgagtacaag cccacggtgc gcc 3313935DNAArtificial Sequenceoligonucleotide C82 139aaatctagat caggcaccgg gcttgcgggt catgc 3514022DNAArtificial Sequenceoligonucleotide C85 140catttccccg aaaagtgcca cc 2214124DNAArtificial Sequenceoligonucleotide D30 141tcactgctag cgagtggtaa actc 2414228DNAArtificial Sequenceoligonucleotide D41 142gaagtcgacg aggcaggcag aagtatgc 2814329DNAArtificial Sequenceoligonucleotide D42 143gagccgcggt ttagttcctc accttgtcg 2914423DNAArtificial Sequenceoligonucleotide D51 144tctggaagct ttgctgaaga aac 2314517DNAArtificial Sequenceoligonucleotide D58 145ccaagttgac cagtgcc 1714619DNAArtificial Sequenceoligonucleotide D70 146tacaagccaa ccacggcct 1914720DNAArtificial Sequenceoligonucleotide D71 147cggaagtgct tgacattggg 2014820DNAArtificial Sequenceoligonucleotide D80 148gttcgtggac acgacctccg 2014921DNAArtificial Sequenceoligonucleotide D89 149gggcaagatg tcgtagtcag g 2115030DNAArtificial Sequenceoligonucleotide D90 150aggcccatgg tcacctccat cgctactgtg 3015120DNAArtificial Sequenceoligonucleotide D91 151ctaatcactc actgtgtaat 2015215DNAArtificial Sequenceoligonucleotide D93 152aattacaggc gcgcc 1515315DNAArtificial Sequenceoligonucleotide D94 153aattggcgcg cctgt 1515425DNAArtificial Sequenceoligonucleotide D95 154tgctttgcat acttctgcct gcctc 2515520DNAArtificial Sequenceoligonucleotide E12 155taggggggat ccaaatgttc 2015620DNAArtificial Sequenceoligonucleotide E13 156cctaaaagaa gatctttagc 2015720DNAArtificial Sequenceoligonucleotide E14 157aagtgttgga tccactttgg 2015820DNAArtificial Sequenceoligonucleotide E15 158tttgaagatc taccaaatgg 2015920DNAArtificial Sequenceoligonucleotide E16 159gttcgggatc cacctggccg 2016020DNAArtificial Sequenceoligonucleotide E17 160taggcaagat cttggccctc 2016120DNAArtificial Sequenceoligonucleotide E18 161cctctctagg gatccgaccc 2016220DNAArtificial Sequenceoligonucleotide E19 162ctagagagat cttccagtat 2016320DNAArtificial Sequenceoligonucleotide E20 163agagttccgg atccgcctgg 2016420DNAArtificial Sequenceoligonucleotide E21 164ccaggcagac tcggaactct 2016520DNAArtificial Sequenceoligonucleotide E22 165tggtgaaacc ggatccctac 2016620DNAArtificial Sequenceoligonucleotide E23 166aggtcaggag atctagacca 2016722DNAArtificial Sequenceoligonucleotide E25 167ccattttcgc ttccttagct cc 2216822DNAArtificial Sequenceoligonucleotide E42 168cgatgtaacc cactcgtgca cc 2216920DNAArtificial Sequenceoligonucleotide E57 169agagatctag gataatttcg 2017036DNAArtificial Sequenceoligonucleotide E92 170aggcgctagc acgcgttcta ctcttttcct actctg 3617135DNAArtificial Sequenceoligonucleotide E93 171gatcaagctt acgcgtctaa aggcatttta tatag 3517235DNAArtificial Sequenceoligonucleotide E94 172aggcgctagc acgcgttcag agttagtgat ccagg 3517335DNAArtificial Sequenceoligonucleotide E95 173gatcaagctt acgcgtcagt aaaggtttcg tatgg 3517436DNAArtificial Sequenceoligonucleotide E96 174aggcgctagc acgcgttcta ctctttcatt actctg 3617526DNAArtificial Sequenceoligonucleotide E97 175cgaggaagct ggagaaggag aagctg 2617625DNAArtificial Sequenceoligonucleotide E98 176caagggccgc agcttacaca tgttc 251776DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 177ccccac 61786DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 178cagcgg 61796DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 179ggcccc 61806DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 180cagccc 61816DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 181gccccc 61826DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 182cggggc 61836DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 183ccccgc 61846DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 184cggcag 61856DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 185agcccc 61866DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 186ccaggg

61876DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 187ggaccc 61886DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 188gcggac 61896DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 189ccagcg 61906DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 190gcagcc 61916DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 191ccggca 61926DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 192agcggc 61936DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 193cagggg 61946DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 194ccgccc 61956DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 195cccccg 61966DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 196gccgcc 61976DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 197gccggc 61986DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 198cggacc 61996DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 199cgcccc 62006DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 200cgccag 62016DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 201cgcagc 62026DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 202cagccg 62036DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 203cccacg 62046DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 204gctgcc 62056DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 205ccctcc 62066DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 206ccctgc 62076DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 207cacccc 62086DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 208gcgcca 62096DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 209aggggc 62106DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 210gagggc 62116DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 211gcgaac 62126DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 212ccggcg 62136DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 213agccgg 62146DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 214ggagcc 62156DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 215ccccag 62166DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 216ccgctc 62176DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 217cccctc 62186DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 218caccgc 62196DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 219ctgccc 62206DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 220gggcca 62216DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 221cgctgc 62226DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 222cagcgc 62236DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 223cggccc 62246DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 224ccgccg 62256DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 225ccccgg 62266DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 226agccgc 62276DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 227gcaccc 62286DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 228aggacc 62296DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 229agggcg 62306DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 230cagggc 62316DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 231cccgcc 62326DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 232gccagc 62336DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 233agcgcc 62346DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 234aggccc 62356DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 235cccacc 62366DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 236cgctca 62376DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 237aacgcg 62386DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 238gcggca 62396DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 239aggtcc 62406DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 240ccgtca 62416DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 241cagagg 62426DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 242cccgag 62436DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 243ccgagg 62446DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 244cgcgga 62456DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 245ccaccc 62466DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 246cctcgc 62476DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 247caagcc 62486DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 248tccgca 62496DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 249cgccgc 62506DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 250gggaac 62516DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 251ccagag 62526DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 252cgttcc 62536DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 253cgagga 62546DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 254gggacc 62556DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 255ccgcga 62566DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 256cctgcg 62576DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 257ctgcgc 62586DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 258gacccc 62596DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 259gctcca 62606DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 260cgccac 62616DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 261gcggga 62626DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 262ctgcga 62636DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 263ctgctc 62646DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 264cagacg 62656DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 265cgagag 62666DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 266cggtgc 62676DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 267ctcccc 62686DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 268gcggcc 62696DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 269cggcgc 62706DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 270aagccc 62716DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 271ccgcag 62726DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 272gcccac 62736DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 273caccca 62746DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 274gcgccc 62756DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 275accggc 62766DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 276ctcgca 62776DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 277acgctc 62786DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 278ctggac 62796DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 279gcccca 62806DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 280accgtc 62816DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 281ccctcg 62826DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 282agcccg 62836DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 283acccga 62846DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 284agcagc 62856DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 285accgcg 62866DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 286cgaggc 62876DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 287agctgc 62886DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 288ggggac 62896DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 289ccgcaa 62906DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 290cgtcgc 62916DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 291cgtgac 62926DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 292cgccca 62936DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 293ctctgc 62946DNAArtificial Sequenceoligonucleotide patterns

over-represented in STAR elements 294agcggg 62956DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 295accgct 62966DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 296cccagg 62976DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 297ccctca 62986DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 298ccccca 62996DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 299ggcgaa 63006DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 300cggctc 63016DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 301ctcgcc 63026DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 302cggaga 63036DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 303tcccca 63046DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 304gacacc 63056DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 305ctccga 63066DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 306ctcgtc 63076DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 307cgacca 63086DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 308atgacg 63096DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 309ccatcg 63106DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 310agggga 63116DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 311gctgca 63126DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 312acccca 63136DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 313cggagc 63146DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 314cctccg 63156DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 315cgggac 63166DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 316cctgga 63176DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 317aggcga 63186DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 318acccct 63196DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 319gctccc 63206DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 320cgtcac 63216DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 321agcgca 63226DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 322gaagcc 63236DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 323gaggcc 63246DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 324accctc 63256DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 325cccggc 63266DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 326cgagaa 63276DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 327ccaccg 63286DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 328acttcg 63296DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 329gatgac 63306DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 330acgagg 63316DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 331ccggag 63326DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 332acccac 63336DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 333ctgggc 63346DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 334ccacgg 63356DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 335cggtcc 63366DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 336agcacc 63376DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 337acaccc 63386DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 338agggcc 63396DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 339cgcgaa 63406DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 340gagccc 63416DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 341ctgagc 63426DNAArtificial Sequenceoligonucleotide patterns over-represented in STAR elements 342aatcgg 63438DNAArtificial SequenceDyad patterns over-represented in STAR elements 343cccnncgg 834412DNAArtificial SequenceDyad patterns over-represented in STAR elements 344ccgnnnnnnc cc 123456DNAArtificial SequenceDyad patterns over-represented in STAR elements 345cagcgg 634621DNAArtificial SequenceDyad patterns over-represented in STAR elements 346cgcnnnnnnn nnnnnnnncc c 2134715DNAArtificial SequenceDyad patterns over-represented in STAR elements 347cggnnnnnnn nngcc 1534815DNAArtificial SequenceDyad patterns over-represented in STAR elements 348cccnnnnnnn nncgc 153497DNAArtificial SequenceDyad patterns over-represented in STAR elements 349cccngcg 73506DNAArtificial SequenceDyad patterns over-represented in STAR elements 350ccccac 635122DNAArtificial SequenceDyad patterns over-represented in STAR elements 351agcnnnnnnn nnnnnnnnnc cg 2235210DNAArtificial SequenceDyad patterns over-represented in STAR elements 352cccnnnncgc 1035319DNAArtificial SequenceDyad patterns over-represented in STAR elements 353cgcnnnnnnn nnnnnngga 1935422DNAArtificial SequenceDyad patterns over-represented in STAR elements 354gcgnnnnnnn nnnnnnnnnc cc 2235511DNAArtificial SequenceDyad patterns over-represented in STAR elements 355cgcnnnnngc a 1135620DNAArtificial SequenceDyad patterns over-represented in STAR elements 356cccnnnnnnn nnnnnnnccc 2035710DNAArtificial SequenceDyad patterns over-represented in STAR elements 357ctgnnnncgc 1035818DNAArtificial SequenceDyad patterns over-represented in STAR elements 358ccannnnnnn nnnnngcg 1835917DNAArtificial SequenceDyad patterns over-represented in STAR elements 359cggnnnnnnn nnnncag 1736011DNAArtificial SequenceDyad patterns over-represented in STAR elements 360cccnnnnngc c 113616DNAArtificial SequenceDyad patterns over-represented in STAR elements 361gccccc 636210DNAArtificial SequenceDyad patterns over-represented in STAR elements 362cgcnnnngac 103636DNAArtificial SequenceDyad patterns over-represented in STAR elements 363cggcag 63649DNAArtificial SequenceDyad patterns over-represented in STAR elements 364cccnnncgc 93657DNAArtificial SequenceDyad patterns over-represented in STAR elements 365cgcngac 73668DNAArtificial SequenceDyad patterns over-represented in STAR elements 366gcgnngcc 836710DNAArtificial SequenceDyad patterns over-represented in STAR elements 367cccnnnngcc 103687DNAArtificial SequenceDyad patterns over-represented in STAR elements 368cccnccc 736919DNAArtificial SequenceDyad patterns over-represented in STAR elements 369ccgnnnnnnn nnnnnncag 1937010DNAArtificial SequenceDyad patterns over-represented in STAR elements 370gccnnnngga 103719DNAArtificial SequenceDyad patterns over-represented in STAR elements 371ccgnnngga 93728DNAArtificial SequenceDyad patterns over-represented in STAR elements 372aggnnggg 837311DNAArtificial SequenceDyad patterns over-represented in STAR elements 373cacnnnnngc g 1137423DNAArtificial SequenceDyad patterns over-represented in STAR elements 374cgcnnnnnnn nnnnnnnnnn cca 2337515DNAArtificial SequenceDyad patterns over-represented in STAR elements 375cccnnnnnnn nnggc 1537611DNAArtificial SequenceDyad patterns over-represented in STAR elements 376cctnnnnngc g 113776DNAArtificial SequenceDyad patterns over-represented in STAR elements 377gcggac 63786DNAArtificial SequenceDyad patterns over-represented in STAR elements 378gccggc 63798DNAArtificial SequenceDyad patterns over-represented in STAR elements 379gcgnnccc 838017DNAArtificial SequenceDyad patterns over-represented in STAR elements 380ccgnnnnnnn nnnnccc 1738114DNAArtificial SequenceDyad patterns over-represented in STAR elements 381cccnnnnnnn ntcg 1438223DNAArtificial SequenceDyad patterns over-represented in STAR elements 382ccgnnnnnnn nnnnnnnnnn gcc 2338311DNAArtificial SequenceDyad patterns over-represented in STAR elements 383gggnnnnngg a 1138412DNAArtificial SequenceDyad patterns over-represented in STAR elements 384ggcnnnnnng ga 1238510DNAArtificial SequenceDyad patterns over-represented in STAR elements 385ccannnnccc 1038620DNAArtificial SequenceDyad patterns over-represented in STAR elements 386cctnnnnnnn nnnnnnnccg 2038718DNAArtificial SequenceDyad patterns over-represented in STAR elements 387gacnnnnnnn nnnnnggc 1838819DNAArtificial SequenceDyad patterns over-represented in STAR elements 388cgcnnnnnnn nnnnnnccc 1938922DNAArtificial SequenceDyad patterns over-represented in STAR elements 389cagnnnnnnn nnnnnnnnnc cc 2239016DNAArtificial SequenceDyad patterns over-represented in STAR elements 390agcnnnnnnn nnnggg 1639119DNAArtificial SequenceDyad patterns over-represented in STAR elements 391cggnnnnnnn nnnnnnggc 193927DNAArtificial SequenceDyad patterns over-represented in STAR elements 392cggngcc 73936DNAArtificial SequenceDyad patterns over-represented in STAR elements 393agcggc 639422DNAArtificial SequenceDyad patterns over-represented in STAR elements 394cccnnnnnnn nnnnnnnnng gc 2239525DNAArtificial SequenceDyad patterns over-represented in STAR elements 395gctnnnnnnn nnnnnnnnnn nnccc 2539622DNAArtificial SequenceDyad patterns over-represented in STAR elements 396cccnnnnnnn nnnnnnnnng gg 2239715DNAArtificial SequenceDyad patterns over-represented in STAR elements 397cccnnnnnnn nncgg 1539816DNAArtificial SequenceDyad patterns over-represented in STAR elements 398cccnnnnnnn nnncgg 163996DNAArtificial SequenceDyad patterns over-represented in STAR elements 399ccagcg 640023DNAArtificial SequenceDyad patterns over-represented in STAR elements 400gccnnnnnnn nnnnnnnnnn cgc 2340112DNAArtificial SequenceDyad patterns over-represented in STAR elements 401cctnnnnnnc gc 124027DNAArtificial SequenceDyad patterns over-represented in STAR elements 402gganccc 740324DNAArtificial SequenceDyad patterns over-represented in STAR elements 403cgcnnnnnnn nnnnnnnnnn ncac 2440426DNAArtificial SequenceDyad patterns over-represented in STAR elements 404cgcnnnnnnn nnnnnnnnnn nnnccg 264056DNAArtificial SequenceDyad patterns over-represented in STAR elements 405ccggca 640626DNAArtificial SequenceDyad patterns over-represented in

STAR elements 406cgcnnnnnnn nnnnnnnnnn nnnccc 2640721DNAArtificial SequenceDyad patterns over-represented in STAR elements 407agcnnnnnnn nnnnnnnncc c 2140813DNAArtificial SequenceDyad patterns over-represented in STAR elements 408cctnnnnnnn ggc 1340911DNAArtificial SequenceDyad patterns over-represented in STAR elements 409gccnnnnncg c 1141020DNAArtificial SequenceDyad patterns over-represented in STAR elements 410gccnnnnnnn nnnnnnncgc 2041117DNAArtificial SequenceDyad patterns over-represented in STAR elements 411cagnnnnnnn nnnnccc 1741222DNAArtificial SequenceDyad patterns over-represented in STAR elements 412gggnnnnnnn nnnnnnnnng ac 2241321DNAArtificial SequenceDyad patterns over-represented in STAR elements 413cccnnnnnnn nnnnnnnngc g 214146DNAArtificial SequenceDyad patterns over-represented in STAR elements 414ccccgc 641522DNAArtificial SequenceDyad patterns over-represented in STAR elements 415cccnnnnnnn nnnnnnnnna gc 2241615DNAArtificial SequenceDyad patterns over-represented in STAR elements 416aggnnnnnnn nnggg 1541718DNAArtificial SequenceDyad patterns over-represented in STAR elements 417cgcnnnnnnn nnnnnctc 1841814DNAArtificial SequenceDyad patterns over-represented in STAR elements 418cacnnnnnnn ncgc 1441913DNAArtificial SequenceDyad patterns over-represented in STAR elements 419ccannnnnnn ccg 134207DNAArtificial SequenceDyad patterns over-represented in STAR elements 420cggngca 742120DNAArtificial SequenceDyad patterns over-represented in STAR elements 421cgcnnnnnnn nnnnnnnccc 204226DNAArtificial SequenceDyad patterns over-represented in STAR elements 422agcccc 642319DNAArtificial SequenceDyad patterns over-represented in STAR elements 423cgcnnnnnnn nnnnnngtc 194249DNAArtificial SequenceDyad patterns over-represented in STAR elements 424gcgnnngca 94256DNAArtificial SequenceDyad patterns over-represented in STAR elements 425cggggc 642620DNAArtificial SequenceDyad patterns over-represented in STAR elements 426gccnnnnnnn nnnnnnnccc 2042713DNAArtificial SequenceDyad patterns over-represented in STAR elements 427accnnnnnnn cgc 1342813DNAArtificial SequenceDyad patterns over-represented in STAR elements 428aggnnnnnnn cgg 1342922DNAArtificial SequenceDyad patterns over-represented in STAR elements 429cccnnnnnnn nnnnnnnnnc ga 2243012DNAArtificial SequenceDyad patterns over-represented in STAR elements 430cgcnnnnnnc ag 1243117DNAArtificial SequenceDyad patterns over-represented in STAR elements 431cagnnnnnnn nnnngcg 1743218DNAArtificial SequenceDyad patterns over-represented in STAR elements 432ccgnnnnnnn nnnnnccg 1843324DNAArtificial SequenceDyad patterns over-represented in STAR elements 433cgcnnnnnnn nnnnnnnnnn ncag 244347DNAArtificial SequenceDyad patterns over-represented in STAR elements 434cagnggg 74356DNAArtificial SequenceDyad patterns over-represented in STAR elements 435cgcccc 643624DNAArtificial SequenceDyad patterns over-represented in STAR elements 436gcgnnnnnnn nnnnnnnnnn ngcc 2443721DNAArtificial SequenceDyad patterns over-represented in STAR elements 437cggnnnnnnn nnnnnnnngg c 2143821DNAArtificial SequenceDyad patterns over-represented in STAR elements 438cccnnnnnnn nnnnnnnnag g 2143926DNAArtificial SequenceDyad patterns over-represented in STAR elements 439aggnnnnnnn nnnnnnnnnn nnngcg 2644011DNAArtificial SequenceDyad patterns over-represented in STAR elements 440cggnnnnnct c 1144123DNAArtificial SequenceDyad patterns over-represented in STAR elements 441tccnnnnnnn nnnnnnnnnn cga 2344210DNAArtificial SequenceDyad patterns over-represented in STAR elements 442gcgnnnnccc 104438DNAArtificial SequenceDyad patterns over-represented in STAR elements 443cccnncgc 84449DNAArtificial SequenceDyad patterns over-represented in STAR elements 444cgtnnncag 944519DNAArtificial SequenceDyad patterns over-represented in STAR elements 445ccgnnnnnnn nnnnnngag 1944612DNAArtificial SequenceDyad patterns over-represented in STAR elements 446ctcnnnnnnc gc 1244710DNAArtificial SequenceDyad patterns over-represented in STAR elements 447cgcnnnngag 1044811DNAArtificial SequenceDyad patterns over-represented in STAR elements 448gcgnnnnngg a 114497DNAArtificial SequenceDyad patterns over-represented in STAR elements 449ccgncag 745017DNAArtificial SequenceDyad patterns over-represented in STAR elements 450cgcnnnnnnn nnnnccg 1745125DNAArtificial SequenceDyad patterns over-represented in STAR elements 451gcgnnnnnnn nnnnnnnnnn nnccc 2545224DNAArtificial SequenceDyad patterns over-represented in STAR elements 452cgcnnnnnnn nnnnnnnnnn ngaa 2445325DNAArtificial SequenceDyad patterns over-represented in STAR elements 453gggnnnnnnn nnnnnnnnnn nngga 254547DNAArtificial SequenceDyad patterns over-represented in STAR elements 454ccancgg 745513DNAArtificial SequenceDyad patterns over-represented in STAR elements 455cccnnnnnnn gcg 1345616DNAArtificial SequenceDyad patterns over-represented in STAR elements 456aggnnnnnnn nnnccc 164576DNAArtificial SequenceDyad patterns over-represented in STAR elements 457ccaggg 645816DNAArtificial SequenceDyad patterns over-represented in STAR elements 458cagnnnnnnn nnnccc 1645924DNAArtificial SequenceDyad patterns over-represented in STAR elements 459ccgnnnnnnn nnnnnnnnnn nccg 2446024DNAArtificial SequenceDyad patterns over-represented in STAR elements 460ccgnnnnnnn nnnnnnnnnn nggc 244618DNAArtificial SequenceDyad patterns over-represented in STAR elements 461cccnngcg 84627DNAArtificial SequenceDyad patterns over-represented in STAR elements 462cgcnggc 746311DNAArtificial SequenceDyad patterns over-represented in STAR elements 463ccgnnnnnga c 114646DNAArtificial SequenceDyad patterns over-represented in STAR elements 464ggaccc 64657DNAArtificial SequenceDyad patterns over-represented in STAR elements 465cccnccg 746621DNAArtificial SequenceDyad patterns over-represented in STAR elements 466cccnnnnnnn nnnnnnnnac g 2146714DNAArtificial SequenceDyad patterns over-represented in STAR elements 467agcnnnnnnn nccc 144689DNAArtificial SequenceDyad patterns over-represented in STAR elements 468cccnnnggc 946915DNAArtificial SequenceDyad patterns over-represented in STAR elements 469aggnnnnnnn nncgg 1547020DNAArtificial SequenceDyad patterns over-represented in STAR elements 470cccnnnnnnn nnnnnnncgc 204716DNAArtificial SequenceDyad patterns over-represented in STAR elements 471ccgccg 647214DNAArtificial SequenceDyad patterns over-represented in STAR elements 472cgcnnnnnnn nagc 1447325DNAArtificial SequenceDyad patterns over-represented in STAR elements 473cgcnnnnnnn nnnnnnnnnn nnacc 2547423DNAArtificial SequenceDyad patterns over-represented in STAR elements 474gcgnnnnnnn nnnnnnnnnn gac 234757DNAArtificial SequenceDyad patterns over-represented in STAR elements 475agcngcg 747617DNAArtificial SequenceDyad patterns over-represented in STAR elements 476ccgnnnnnnn nnnnggc 1747710DNAArtificial SequenceDyad patterns over-represented in STAR elements 477cggnnnnaga 1047820DNAArtificial SequenceDyad patterns over-represented in STAR elements 478cgcnnnnnnn nnnnnnnccg 2047926DNAArtificial SequenceDyad patterns over-represented in STAR elements 479cctnnnnnnn nnnnnnnnnn nnngcg 2648016DNAArtificial SequenceDyad patterns over-represented in STAR elements 480ccannnnnnn nnncgc 1648126DNAArtificial SequenceDyad patterns over-represented in STAR elements 481cccnnnnnnn nnnnnnnnnn nnncac 2648217DNAArtificial SequenceDyad patterns over-represented in STAR elements 482ccgnnnnnnn nnnngcc 1748324DNAArtificial SequenceDyad patterns over-represented in STAR elements 483cgcnnnnnnn nnnnnnnnnn nccc 2448421DNAArtificial SequenceDyad patterns over-represented in STAR elements 484cggnnnnnnn nnnnnnnncg c 2148522DNAArtificial SequenceDyad patterns over-represented in STAR elements 485cgcnnnnnnn nnnnnnnnng cc 2248626DNAArtificial SequenceDyad patterns over-represented in STAR elements 486cgcnnnnnnn nnnnnnnnnn nnnggc 2648725DNAArtificial SequenceDyad patterns over-represented in STAR elements 487cgcnnnnnnn nnnnnnnnnn nnccg 2548816DNAArtificial SequenceDyad patterns over-represented in STAR elements 488cggnnnnnnn nnncca 1648923DNAArtificial SequenceDyad patterns over-represented in STAR elements 489cgcnnnnnnn nnnnnnnnnn ccc 2349017DNAArtificial SequenceDyad patterns over-represented in STAR elements 490cgcnnnnnnn nnnnaca 174916DNAArtificial SequenceDyad patterns over-represented in STAR elements 491cggacc 649216DNAArtificial SequenceDyad patterns over-represented in STAR elements 492gcgnnnnnnn nnngcc 1649314DNAArtificial SequenceDyad patterns over-represented in STAR elements 493gcgnnnnnnn ngac 1449421DNAArtificial SequenceDyad patterns over-represented in STAR elements 494cccnnnnnnn nnnnnnnngg g 2149522DNAArtificial SequenceDyad patterns over-represented in STAR elements 495cggnnnnnnn nnnnnnnnng gc 2249622DNAArtificial SequenceDyad patterns over-represented in STAR elements 496cgcnnnnnnn nnnnnnnnnc ca 224979DNAArtificial SequenceDyad patterns over-represented in STAR elements 497gccnnnccc 949810DNAArtificial SequenceDyad patterns over-represented in STAR elements 498cagnnnnggg 1049912DNAArtificial SequenceDyad patterns over-represented in STAR elements 499cccnnnnnng cg 1250022DNAArtificial SequenceDyad patterns over-represented in STAR elements 500ccgnnnnnnn nnnnnnnnnc gc 2250123DNAArtificial SequenceDyad patterns over-represented in STAR elements 501cccnnnnnnn nnnnnnnnnn gca 2350219DNAArtificial SequenceDyad patterns over-represented in STAR elements 502cgcnnnnnnn nnnnnntcc 195037DNAArtificial SequenceDyad patterns over-represented in STAR elements 503gccncgc 750425DNAArtificial SequenceDyad patterns over-represented in STAR elements 504ccgnnnnnnn nnnnnnnnnn nngag 2550516DNAArtificial SequenceDyad patterns over-represented in STAR elements 505gggnnnnnnn nnngga 1650611DNAArtificial SequenceDyad patterns over-represented in STAR elements 506cagnnnnncc g 115079DNAArtificial SequenceDyad patterns over-represented in STAR elements 507cgcnnnaga 95086DNAArtificial SequenceDyad patterns over-represented in STAR elements 508gccgcc 650914DNAArtificial SequenceDyad patterns over-represented in STAR elements 509cccnnnnnnn nggc 1451012DNAArtificial SequenceDyad patterns over-represented in STAR elements 510cctnnnnnng cg 1251112DNAArtificial SequenceDyad patterns over-represented in STAR elements 511gacnnnnnnc cc 125127DNAArtificial SequenceDyad patterns over-represented in STAR elements 512cggnccc 751321DNAArtificial SequenceDyad patterns over-represented in STAR elements 513cccnnnnnnn nnnnnnnncc g 2151415DNAArtificial SequenceDyad patterns over-represented in STAR elements 514cagnnnnnnn nnccc 1551516DNAArtificial SequenceDyad patterns over-represented in STAR elements 515cggnnnnnnn nnnggc 1651616DNAArtificial SequenceDyad patterns over-represented in STAR elements 516cgannnnnnn nnnacg 165179DNAArtificial SequenceDyad patterns over-represented in STAR elements 517gcgnnntcc 95189DNAArtificial SequenceDyad patterns over-represented in STAR elements 518cccnnngcc 95197DNAArtificial SequenceDyad patterns over-represented in STAR elements 519gcgnacc 752015DNAArtificial SequenceDyad patterns over-represented in STAR elements 520ccgnnnnnnn nnagg 1552122DNAArtificial SequenceDyad patterns over-represented in STAR elements 521cgcnnnnnnn nnnnnnnnnc ag 225226DNAArtificial SequenceDyad patterns

over-represented in STAR elements 522ggcccc 652318DNAArtificial SequenceDyad patterns over-represented in STAR elements 523aggnnnnnnn nnnnnccg 185246DNAArtificial SequenceDyad patterns over-represented in STAR elements 524ccggcg 65258DNAArtificial SequenceDyad patterns over-represented in STAR elements 525ccgnngcc 852617DNAArtificial SequenceDyad patterns over-represented in STAR elements 526ccgnnnnnnn nnnngtc 175276DNAArtificial SequenceDyad patterns over-represented in STAR elements 527cagccc 652811DNAArtificial SequenceDyad patterns over-represented in STAR elements 528cccnnnnncc g 1152926DNAArtificial SequenceDyad patterns over-represented in STAR elements 529gccnnnnnnn nnnnnnnnnn nnnccc 265308DNAArtificial SequenceDyad patterns over-represented in STAR elements 530gacnncgc 853112DNAArtificial SequenceDyad patterns over-represented in STAR elements 531cgcnnnnnnc ac 1253220DNAArtificial SequenceDyad patterns over-represented in STAR elements 532aggnnnnnnn nnnnnnngcg 2053311DNAArtificial SequenceDyad patterns over-represented in STAR elements 533gacnnnnncg c 1153425DNAArtificial SequenceDyad patterns over-represented in STAR elements 534cctnnnnnnn nnnnnnnnnn nnccg 2553518DNAArtificial SequenceDyad patterns over-represented in STAR elements 535ccgnnnnnnn nnnnngga 1853615DNAArtificial SequenceDyad patterns over-represented in STAR elements 536ggcnnnnnnn nngac 1553716DNAArtificial SequenceDyad patterns over-represented in STAR elements 537aggnnnnnnn nnnggg 1653816DNAArtificial SequenceDyad patterns over-represented in STAR elements 538ccgnnnnnnn nnngag 1653912DNAArtificial SequenceDyad patterns over-represented in STAR elements 539cgcnnnnnng ga 1254013DNAArtificial SequenceDyad patterns over-represented in STAR elements 540cgcnnnnnnn agc 1354119DNAArtificial SequenceDyad patterns over-represented in STAR elements 541ccannnnnnn nnnnnncgg 1954212DNAArtificial SequenceDyad patterns over-represented in STAR elements 542cggnnnnnng ga 1254325DNAArtificial SequenceDyad patterns over-represented in STAR elements 543cgcnnnnnnn nnnnnnnnnn nngcc 2554418DNAArtificial SequenceDyad patterns over-represented in STAR elements 544ccannnnnnn nnnnncgc 185457DNAArtificial SequenceDyad patterns over-represented in STAR elements 545cggnggc 75469DNAArtificial SequenceDyad patterns over-represented in STAR elements 546gcgnnncca 95477DNAArtificial SequenceDyad patterns over-represented in STAR elements 547aggncgc 754811DNAArtificial SequenceDyad patterns over-represented in STAR elements 548ctcnnnnncg c 115496DNAArtificial SequenceDyad patterns over-represented in STAR elements 549cccacg 655023DNAArtificial SequenceDyad patterns over-represented in STAR elements 550cagnnnnnnn nnnnnnnnnn ccg 2355110DNAArtificial SequenceDyad patterns over-represented in STAR elements 551ggcnnnnccc 1055214DNAArtificial SequenceDyad patterns over-represented in STAR elements 552aggnnnnnnn ngcg 145537DNAArtificial SequenceDyad patterns over-represented in STAR elements 553ctgnccc 755422DNAArtificial SequenceDyad patterns over-represented in STAR elements 554cccnnnnnnn nnnnnnnnnc ag 2255515DNAArtificial SequenceDyad patterns over-represented in STAR elements 555cgcnnnnnnn nngac 1555612DNAArtificial SequenceDyad patterns over-represented in STAR elements 556cagnnnnnnc cg 1255718DNAArtificial SequenceDyad patterns over-represented in STAR elements 557cgtnnnnnnn nnnnncgc 1855813DNAArtificial SequenceDyad patterns over-represented in STAR elements 558ctcnnnnnnn gcc 1355925DNAArtificial SequenceDyad patterns over-represented in STAR elements 559cgcnnnnnnn nnnnnnnnnn nntcc 2556013DNAArtificial SequenceDyad patterns over-represented in STAR elements 560cccnnnnnnn gcc 1356119DNAArtificial SequenceDyad patterns over-represented in STAR elements 561cagnnnnnnn nnnnnncgg 195627DNAArtificial SequenceDyad patterns over-represented in STAR elements 562cgcngcc 756323DNAArtificial SequenceDyad patterns over-represented in STAR elements 563cgcnnnnnnn nnnnnnnnnn ccg 2356410DNAArtificial SequenceDyad patterns over-represented in STAR elements 564aggnnnnccc 1056516DNAArtificial SequenceDyad patterns over-represented in STAR elements 565agcnnnnnnn nnncgc 1656617DNAArtificial SequenceDyad patterns over-represented in STAR elements 566cccnnnnnnn nnnncgg 1756714DNAArtificial SequenceDyad patterns over-represented in STAR elements 567cccnnnnnnn ngcc 145687DNAArtificial SequenceDyad patterns over-represented in STAR elements 568ccgncgg 75697DNAArtificial SequenceDyad patterns over-represented in STAR elements 569cccnacc 75706DNAArtificial SequenceDyad patterns over-represented in STAR elements 570cgccag 657125DNAArtificial SequenceDyad patterns over-represented in STAR elements 571ccgnnnnnnn nnnnnnnnnn nntgc 2557210DNAArtificial SequenceDyad patterns over-represented in STAR elements 572gcgnnnncga 1057325DNAArtificial SequenceDyad patterns over-represented in STAR elements 573ccgnnnnnnn nnnnnnnnnn nngcc 2557416DNAArtificial SequenceDyad patterns over-represented in STAR elements 574ccannnnnnn nnnccc 1657519DNAArtificial SequenceDyad patterns over-represented in STAR elements 575cagnnnnnnn nnnnnnggg 1957624DNAArtificial SequenceDyad patterns over-represented in STAR elements 576agcnnnnnnn nnnnnnnnnn ncgg 2457714DNAArtificial SequenceDyad patterns over-represented in STAR elements 577cgannnnnnn ncgc 1457810DNAArtificial SequenceDyad patterns over-represented in STAR elements 578agcnnnnccc 1057912DNAArtificial SequenceDyad patterns over-represented in STAR elements 579ggannnnnnc cc 1258019DNAArtificial SequenceDyad patterns over-represented in STAR elements 580cggnnnnnnn nnnnnnaag 1958117DNAArtificial SequenceDyad patterns over-represented in STAR elements 581accnnnnnnn nnnncgc 1758218DNAArtificial SequenceDyad patterns over-represented in STAR elements 582ccgnnnnnnn nnnnncag 1858318DNAArtificial SequenceDyad patterns over-represented in STAR elements 583cccnnnnnnn nnnnnggg 1858423DNAArtificial SequenceDyad patterns over-represented in STAR elements 584cacnnnnnnn nnnnnnnnnn acg 2358524DNAArtificial SequenceDyad patterns over-represented in STAR elements 585cagnnnnnnn nnnnnnnnnn nccc 2458616DNAArtificial SequenceDyad patterns over-represented in STAR elements 586cgtnnnnnnn nnngtc 1658719DNAArtificial SequenceDyad patterns over-represented in STAR elements 587cccnnnnnnn nnnnnngcg 195887DNAArtificial SequenceDyad patterns over-represented in STAR elements 588gcancgc 758910DNAArtificial SequenceDyad patterns over-represented in STAR elements 589agannnnccg 1059016DNAArtificial SequenceDyad patterns over-represented in STAR elements 590gcgnnnnnnn nnnagc 165916DNAArtificial SequenceDyad patterns over-represented in STAR elements 591cgcgga 659210DNAArtificial SequenceDyad patterns over-represented in STAR elements 592cggnnnngac 1059318DNAArtificial SequenceDyad patterns over-represented in STAR elements 593cccnnnnnnn nnnnncgc 1859421DNAArtificial SequenceDyad patterns over-represented in STAR elements 594gccnnnnnnn nnnnnnnncc c 2159512DNAArtificial SequenceDyad patterns over-represented in STAR elements 595gcgnnnnnnt cc 125969DNAArtificial SequenceDyad patterns over-represented in STAR elements 596cggnnncag 95979DNAArtificial SequenceDyad patterns over-represented in STAR elements 597cccnnncca 95989DNAArtificial SequenceDyad patterns over-represented in STAR elements 598agcnnnccc 959922DNAArtificial SequenceDyad patterns over-represented in STAR elements 599gggnnnnnnn nnnnnnnnng ca 2260014DNAArtificial SequenceDyad patterns over-represented in STAR elements 600aggnnnnnnn nccg 146016DNAArtificial SequenceDyad patterns over-represented in STAR elements 601cccccg 660211DNAArtificial SequenceDyad patterns over-represented in STAR elements 602gcgnnnnnga c 1160315DNAArtificial SequenceDyad patterns over-represented in STAR elements 603cccnnnnnnn nnacc 1560411DNAArtificial SequenceDyad patterns over-represented in STAR elements 604ctgnnnnncg c 1160520DNAArtificial SequenceDyad patterns over-represented in STAR elements 605cgcnnnnnnn nnnnnnnctc 2060620DNAArtificial SequenceDyad patterns over-represented in STAR elements 606cggnnnnnnn nnnnnnngca 2060714DNAArtificial SequenceDyad patterns over-represented in STAR elements 607ccgnnnnnnn ngcc 1460813DNAArtificial SequenceDyad patterns over-represented in STAR elements 608ccgnnnnnnn cac 1360914DNAArtificial SequenceDyad patterns over-represented in STAR elements 609agcnnnnnnn ngcg 1461022DNAArtificial SequenceDyad patterns over-represented in STAR elements 610cggnnnnnnn nnnnnnnnng ga 2261118DNAArtificial SequenceDyad patterns over-represented in STAR elements 611ccannnnnnn nnnnnccg 186128DNAArtificial SequenceDyad patterns over-represented in STAR elements 612cggnnccc 861319DNAArtificial SequenceDyad patterns over-represented in STAR elements 613ccannnnnnn nnnnnnggg 1961421DNAArtificial SequenceDyad patterns over-represented in STAR elements 614cggnnnnnnn nnnnnnnngc a 2161515DNAArtificial SequenceDyad patterns over-represented in STAR elements 615cgcnnnnnnn nngca 1561625DNAArtificial SequenceDyad patterns over-represented in STAR elements 616cggnnnnnnn nnnnnnnnnn nncca 2561721DNAArtificial SequenceDyad patterns over-represented in STAR elements 617gggnnnnnnn nnnnnnnncg a 2161816DNAArtificial SequenceDyad patterns over-represented in STAR elements 618cccnnnnnnn nnncgc 1661920DNAArtificial SequenceDyad patterns over-represented in STAR elements 619ctcnnnnnnn nnnnnnncgc 2062017DNAArtificial SequenceDyad patterns over-represented in STAR elements 620cacnnnnnnn nnnngcg 176218DNAArtificial SequenceDyad patterns over-represented in STAR elements 621ccgnnggc 862224DNAArtificial SequenceDyad patterns over-represented in STAR elements 622ctgnnnnnnn nnnnnnnnnn nccc 2462319DNAArtificial SequenceDyad patterns over-represented in STAR elements 623gggnnnnnnn nnnnnncac 1962421DNAArtificial SequenceDyad patterns over-represented in STAR elements 624cctnnnnnnn nnnnnnnngg c 2162526DNAArtificial SequenceDyad patterns over-represented in STAR elements 625cccnnnnnnn nnnnnnnnnn nnncga 2662614DNAArtificial SequenceDyad patterns over-represented in STAR elements 626cccnnnnnnn ncga 1462713DNAArtificial SequenceDyad patterns over-represented in STAR elements 627gagnnnnnnn ccc 136288DNAArtificial SequenceDyad patterns over-represented in STAR elements 628cgcnnccg 86296DNAArtificial SequenceDyad patterns over-represented in STAR elements 629ccctcc 66306DNAArtificial SequenceDyad patterns over-represented in STAR elements 630agcgcc 66318DNAArtificial SequenceDyad patterns over-represented in STAR elements 631cccnntcc 863211DNAArtificial SequenceDyad patterns over-represented in STAR elements 632ccgnnnnncc c 1163319DNAArtificial SequenceDyad patterns over-represented in STAR elements 633cgcnnnnnnn nnnnnncgc 196347DNAArtificial SequenceDyad patterns over-represented in STAR elements 634cccncgc 763522DNAArtificial SequenceDyad patterns over-represented in STAR elements 635gccnnnnnnn nnnnnnnnng ca 2263622DNAArtificial SequenceDyad patterns over-represented in STAR elements 636cccnnnnnnn nnnnnnnnnc ca 2263719DNAArtificial SequenceDyad patterns over-represented in STAR elements 637ccgnnnnnnn nnnnnncgc 1963823DNAArtificial

SequenceDyad patterns over-represented in STAR elements 638ccgnnnnnnn nnnnnnnnnn cag 2363924DNAArtificial SequenceDyad patterns over-represented in STAR elements 639cggnnnnnnn nnnnnnnnnn nggc 2464020DNAArtificial SequenceDyad patterns over-represented in STAR elements 640ccgnnnnnnn nnnnnnnagg 2064111DNAArtificial SequenceDyad patterns over-represented in STAR elements 641cccnnnnncg g 1164212DNAArtificial SequenceDyad patterns over-represented in STAR elements 642cccnnnnnng ga 126438DNAArtificial SequenceDyad patterns over-represented in STAR elements 643acgnnccc 864415DNAArtificial SequenceDyad patterns over-represented in STAR elements 644ccannnnnnn nnccg 1564525DNAArtificial SequenceDyad patterns over-represented in STAR elements 645cccnnnnnnn nnnnnnnnnn nncca 256466DNAArtificial SequenceDyad patterns over-represented in STAR elements 646cagggg 66477DNAArtificial SequenceDyad patterns over-represented in STAR elements 647agcnccc 764813DNAArtificial SequenceDyad patterns over-represented in STAR elements 648gcgnnnnnnn tcc 1364924DNAArtificial SequenceDyad patterns over-represented in STAR elements 649acgnnnnnnn nnnnnnnnnn ncca 2465020DNAArtificial SequenceDyad patterns over-represented in STAR elements 650gctnnnnnnn nnnnnnnccc 2065120DNAArtificial SequenceDyad patterns over-represented in STAR elements 651gcgnnnnnnn nnnnnnnccc 2065225DNAArtificial SequenceDyad patterns over-represented in STAR elements 652gcgnnnnnnn nnnnnnnnnn nnagc 2565314DNAArtificial SequenceDyad patterns over-represented in STAR elements 653ccgnnnnnnn ncag 1465412DNAArtificial SequenceDyad patterns over-represented in STAR elements 654gcgnnnnnng cc 1265516DNAArtificial SequenceDyad patterns over-represented in STAR elements 655gcgnnnnnnn nnngca 1665613DNAArtificial SequenceDyad patterns over-represented in STAR elements 656cctnnnnnnn gcc 1365719DNAArtificial SequenceDyad patterns over-represented in STAR elements 657gccnnnnnnn nnnnnngcc 1965820DNAArtificial SequenceDyad patterns over-represented in STAR elements 658cccnnnnnnn nnnnnnngcc 2065921DNAArtificial SequenceDyad patterns over-represented in STAR elements 659cccnnnnnnn nnnnnnnncg g 2166019DNAArtificial SequenceDyad patterns over-represented in STAR elements 660ccannnnnnn nnnnnncgc 1966117DNAArtificial SequenceDyad patterns over-represented in STAR elements 661agcnnnnnnn nnnnggg 176626DNAArtificial SequenceDyad patterns over-represented in STAR elements 662ggagcc 66639DNAArtificial SequenceDyad patterns over-represented in STAR elements 663gccnnntcc 966411DNAArtificial SequenceDyad patterns over-represented in STAR elements 664cctnnnnngc c 1166524DNAArtificial SequenceDyad patterns over-represented in STAR elements 665cggnnnnnnn nnnnnnnnnn nccc 246669DNAArtificial SequenceDyad patterns over-represented in STAR elements 666cctnnnggc 96676DNAArtificial SequenceDyad patterns over-represented in STAR elements 667ccgctc 666823DNAArtificial SequenceDyad patterns over-represented in STAR elements 668agcnnnnnnn nnnnnnnnnn gcg 2366920DNAArtificial SequenceDyad patterns over-represented in STAR elements 669acgnnnnnnn nnnnnnnggg 2067018DNAArtificial SequenceDyad patterns over-represented in STAR elements 670cgannnnnnn nnnnnggc 1867126DNAArtificial SequenceDyad patterns over-represented in STAR elements 671cccnnnnnnn nnnnnnnnnn nnncgc 2667218DNAArtificial SequenceDyad patterns over-represented in STAR elements 672acgnnnnnnn nnnnnctg 186736DNAArtificial SequenceDyad patterns over-represented in STAR elements 673ccgccc 667416DNAArtificial SequenceDyad patterns over-represented in STAR elements 674ccgnnnnnnn nnngga 166759DNAArtificial SequenceDyad patterns over-represented in STAR elements 675cccnnngcg 967620DNAArtificial SequenceDyad patterns over-represented in STAR elements 676gcgnnnnnnn nnnnnnncgc 2067714DNAArtificial SequenceDyad patterns over-represented in STAR elements 677ccgnnnnnnn ncgc 1467816DNAArtificial SequenceDyad patterns over-represented in STAR elements 678cgcnnnnnnn nnnaca 1667925DNAArtificial SequenceDyad patterns over-represented in STAR elements 679cccnnnnnnn nnnnnnnnnn nnccg 2568020DNAArtificial SequenceDyad patterns over-represented in STAR elements 680cacnnnnnnn nnnnnnncgc 206819DNAArtificial SequenceDyad patterns over-represented in STAR elements 681gacnnnggc 968213DNAArtificial SequenceDyad patterns over-represented in STAR elements 682gaannnnnnn cgc 1368322DNAArtificial SequenceDyad patterns over-represented in STAR elements 683cgcnnnnnnn nnnnnnnnng gc 2268415DNAArtificial SequenceDyad patterns over-represented in STAR elements 684ggcnnnnnnn nnccc 1568515DNAArtificial SequenceDyad patterns over-represented in STAR elements 685cccnnnnnnn nngcc 156866DNAArtificial SequenceDyad patterns over-represented in STAR elements 686cgctgc 668714DNAArtificial SequenceDyad patterns over-represented in STAR elements 687cctnnnnnnn nggc 1468814DNAArtificial SequenceDyad patterns over-represented in STAR elements 688ccannnnnnn nccc 146898DNAArtificial SequenceDyad patterns over-represented in STAR elements 689gacnnccc 86907DNAArtificial SequenceDyad patterns over-represented in STAR elements 690ggcnccc 76916DNAArtificial SequenceDyad patterns over-represented in STAR elements 691cgcagc 669210DNAArtificial SequenceDyad patterns over-represented in STAR elements 692aggnnnngcg 1069312DNAArtificial SequenceDyad patterns over-represented in STAR elements 693cggnnnnnnt cc 1269425DNAArtificial SequenceDyad patterns over-represented in STAR elements 694acgnnnnnnn nnnnnnnnnn nnggc 2569514DNAArtificial SequenceDyad patterns over-represented in STAR elements 695cccnnnnnnn nacg 1469624DNAArtificial SequenceDyad patterns over-represented in STAR elements 696cccnnnnnnn nnnnnnnnnn ngcc 246978DNAArtificial SequenceDyad patterns over-represented in STAR elements 697gccnncga 869814DNAArtificial SequenceDyad patterns over-represented in STAR elements 698cccnnnnnnn ngcg 146996DNAArtificial SequenceDyad patterns over-represented in STAR elements 699cccctc 670017DNAArtificial SequenceDyad patterns over-represented in STAR elements 700gccnnnnnnn nnnncgc 1770115DNAArtificial SequenceDyad patterns over-represented in STAR elements 701agcnnnnnnn nnccc 157026DNAArtificial SequenceDyad patterns over-represented in STAR elements 702gctgcc 67039DNAArtificial SequenceDyad patterns over-represented in STAR elements 703cgcnnnccc 97048DNAArtificial SequenceDyad patterns over-represented in STAR elements 704cccnnccc 870515DNAArtificial SequenceDyad patterns over-represented in STAR elements 705gccnnnnnnn nncgc 1570625DNAArtificial SequenceDyad patterns over-represented in STAR elements 706gcannnnnnn nnnnnnnnnn nncgc 2570710DNAArtificial SequenceDyad patterns over-represented in STAR elements 707cagnnnncgg 107088DNAArtificial SequenceDyad patterns over-represented in STAR elements 708cagnnggg 870922DNAArtificial SequenceDyad patterns over-represented in STAR elements 709gccnnnnnnn nnnnnnnnnc cc 2271011DNAArtificial SequenceDyad patterns over-represented in STAR elements 710gagnnnnncc c 1171122DNAArtificial SequenceDyad patterns over-represented in STAR elements 711cctnnnnnnn nnnnnnnnnt cg 227129DNAArtificial SequenceDyad patterns over-represented in STAR elements 712cccnnnggc 971319DNAArtificial SequenceDyad patterns over-represented in STAR elements 713gcgnnnnnnn nnnnnngga 1971423DNAArtificial SequenceDyad patterns over-represented in STAR elements 714gccnnnnnnn nnnnnnnnnn ggc 2371520DNAArtificial SequenceDyad patterns over-represented in STAR elements 715cccnnnnnnn nnnnnnnggc 207169DNAArtificial SequenceDyad patterns over-represented in STAR elements 716aggnnnccg 97176DNAArtificial SequenceDyad patterns over-represented in STAR elements 717caccgc 671824DNAArtificial SequenceDyad patterns over-represented in STAR elements 718cggnnnnnnn nnnnnnnnnn ncag 247197DNAArtificial SequenceDyad patterns over-represented in STAR elements 719agcngcc 772024DNAArtificial SequenceDyad patterns over-represented in STAR elements 720cgcnnnnnnn nnnnnnnnnn nggc 2472111DNAArtificial SequenceDyad patterns over-represented in STAR elements 721cccnnnnnag g 117226DNAArtificial SequenceDyad patterns over-represented in STAR elements 722aacgcg 672316DNAArtificial SequenceDyad patterns over-represented in STAR elements 723cccnnnnnnn nnncca 1672419DNAArtificial SequenceDyad patterns over-represented in STAR elements 724cgcnnnnnnn nnnnnngag 1972513DNAArtificial SequenceDyad patterns over-represented in STAR elements 725cgcnnnnnnn gcc 1372615DNAArtificial SequenceDyad patterns over-represented in STAR elements 726cccnnnnnnn nnccg 1572722DNAArtificial SequenceDyad patterns over-represented in STAR elements 727cgcnnnnnnn nnnnnnnnnc cc 2272819DNAArtificial SequenceDyad patterns over-represented in STAR elements 728gaannnnnnn nnnnnncgc 197299DNAArtificial SequenceDyad patterns over-represented in STAR elements 729ggcnnnccc 973017DNAArtificial SequenceDyad patterns over-represented in STAR elements 730tccnnnnnnn nnnncca 177316DNAArtificial SequenceDyad patterns over-represented in STAR elements 731cacccc 673222DNAArtificial SequenceDyad patterns over-represented in STAR elements 732cgcnnnnnnn nnnnnnnnnc cg 2273321DNAArtificial SequenceDyad patterns over-represented in STAR elements 733cggnnnnnnn nnnnnnnnag c 2173418DNAArtificial SequenceDyad patterns over-represented in STAR elements 734cccnnnnnnn nnnnngcg 1873515DNAArtificial SequenceDyad patterns over-represented in STAR elements 735cccnnnnnnn nngag 1573626DNAArtificial SequenceDyad patterns over-represented in STAR elements 736ccgnnnnnnn nnnnnnnnnn nnntcc 267376DNAArtificial SequenceDyad patterns over-represented in STAR elements 737cgccgc 673813DNAArtificial SequenceDyad patterns over-represented in STAR elements 738atgnnnnnnn cgg 1373926DNAArtificial SequenceDyad patterns over-represented in STAR elements 739gggnnnnnnn nnnnnnnnnn nnngca 2674010DNAArtificial SequenceDyad patterns over-represented in STAR elements 740cggnnnnggc 1074122DNAArtificial SequenceDyad patterns over-represented in STAR elements 741cggnnnnnnn nnnnnnnnna gc 2274211DNAArtificial SequenceDyad patterns over-represented in STAR elements 742cggnnnnngg c 117436DNAArtificial SequenceDyad patterns over-represented in STAR elements 743gcggga 674426DNAArtificial SequenceDyad patterns over-represented in STAR elements 744ggcnnnnnnn nnnnnnnnnn nnncac 2674515DNAArtificial SequenceDyad patterns over-represented in STAR elements 745cccnnnnnnn nnccc 1574623DNAArtificial SequenceDyad patterns over-represented in STAR elements 746accnnnnnnn nnnnnnnnnn ggc 2374712DNAArtificial SequenceDyad patterns over-represented in STAR elements 747cccnnnnnnc ga 1274816DNAArtificial SequenceDyad patterns over-represented in STAR elements 748aagnnnnnnn nnncgg 1674923DNAArtificial SequenceDyad patterns over-represented in STAR elements 749cgcnnnnnnn nnnnnnnnnn cac 2375022DNAArtificial SequenceDyad patterns over-represented in STAR elements 750cccnnnnnnn nnnnnnnnnc gg 2275124DNAArtificial SequenceDyad patterns over-represented in STAR elements 751gacnnnnnnn nnnnnnnnnn nggc 2475221DNAArtificial SequenceDyad patterns over-represented in STAR elements 752gggnnnnnnn nnnnnnnnga c 2175310DNAArtificial SequenceDyad patterns over-represented in STAR elements 753gccnnnntcc

1075421DNAArtificial SequenceDyad patterns over-represented in STAR elements 754ggcnnnnnnn nnnnnnnncc c 2175518DNAArtificial SequenceDyad patterns over-represented in STAR elements 755cagnnnnnnn nnnnncgc 187569DNAArtificial SequenceDyad patterns over-represented in STAR elements 756ccannngcg 975722DNAArtificial SequenceDyad patterns over-represented in STAR elements 757ccgnnnnnnn nnnnnnnnng ag 227588DNAArtificial SequenceDyad patterns over-represented in STAR elements 758agcnncgc 875910DNAArtificial SequenceDyad patterns over-represented in STAR elements 759gagnnnnccc 107609DNAArtificial SequenceDyad patterns over-represented in STAR elements 760aggnnncgc 976119DNAArtificial SequenceDyad patterns over-represented in STAR elements 761cacnnnnnnn nnnnnnagg 1976210DNAArtificial SequenceDyad patterns over-represented in STAR elements 762cccnnnncag 107638DNAArtificial SequenceDyad patterns over-represented in STAR elements 763cccnngaa 876425DNAArtificial SequenceDyad patterns over-represented in STAR elements 764cgcnnnnnnn nnnnnnnnnn nngag 2576524DNAArtificial SequenceDyad patterns over-represented in STAR elements 765acgnnnnnnn nnnnnnnnnn nggg 2476610DNAArtificial SequenceDyad patterns over-represented in STAR elements 766cccnnnnggc 1076715DNAArtificial SequenceDyad patterns over-represented in STAR elements 767cggnnnnnnn nngag 157689DNAArtificial SequenceDyad patterns over-represented in STAR elements 768cccnnnggg 976910DNAArtificial SequenceDyad patterns over-represented in STAR elements 769gagnnnnggc 1077011DNAArtificial SequenceDyad patterns over-represented in STAR elements 770cgcnnnnnga g 1177126DNAArtificial SequenceDyad patterns over-represented in STAR elements 771ccgnnnnnnn nnnnnnnnnn nnnagg 2677221DNAArtificial SequenceDyad patterns over-represented in STAR elements 772cccnnnnnnn nnnnnnnncc c 2177323DNAArtificial SequenceDyad patterns over-represented in STAR elements 773aggnnnnnnn nnnnnnnnnn ccg 2377412DNAArtificial SequenceDyad patterns over-represented in STAR elements 774aggnnnnnng gg 1277526DNAArtificial SequenceDyad patterns over-represented in STAR elements 775ggcnnnnnnn nnnnnnnnnn nnnccc 2677623DNAArtificial SequenceDyad patterns over-represented in STAR elements 776gcannnnnnn nnnnnnnnnn cgc 2377717DNAArtificial SequenceDyad patterns over-represented in STAR elements 777cgannnnnnn nnnnacg 177788DNAArtificial SequenceDyad patterns over-represented in STAR elements 778cgcnngga 877911DNAArtificial SequenceDyad patterns over-represented in STAR elements 779ctgnnnnncc c 1178026DNAArtificial SequenceDyad patterns over-represented in STAR elements 780tccnnnnnnn nnnnnnnnnn nnncca 267818DNAArtificial SequenceDyad patterns over-represented in STAR elements 781ccannggg 878221DNAArtificial SequenceDyad patterns over-represented in STAR elements 782ccgnnnnnnn nnnnnnnngc g 2178311DNAArtificial SequenceDyad patterns over-represented in STAR elements 783ccannnnngg g 117847DNAArtificial SequenceDyad patterns over-represented in STAR elements 784cggntgc 778520DNAArtificial SequenceDyad patterns over-represented in STAR elements 785cccnnnnnnn nnnnnnngcg 207866DNAArtificial SequenceDyad patterns over-represented in STAR elements 786cagccg 678715DNAArtificial SequenceDyad patterns over-represented in STAR elements 787gccnnnnnnn nntcc 1578826DNAArtificial SequenceDyad patterns over-represented in STAR elements 788aggnnnnnnn nnnnnnnnnn nnncgc 2678912DNAArtificial SequenceDyad patterns over-represented in STAR elements 789cccnnnnnng ac 1279017DNAArtificial SequenceDyad patterns over-represented in STAR elements 790cggnnnnnnn nnnncca 1779120DNAArtificial SequenceDyad patterns over-represented in STAR elements 791gggnnnnnnn nnnnnnncac 2079221DNAArtificial SequenceDyad patterns over-represented in STAR elements 792gcannnnnnn nnnnnnnncg c 217938DNAArtificial SequenceDyad patterns over-represented in STAR elements 793cgcnnaca 879415DNAArtificial SequenceDyad patterns over-represented in STAR elements 794accnnnnnnn nnccc 1579515DNAArtificial SequenceDyad patterns over-represented in STAR elements 795gcgnnnnnnn nncgc 1579621DNAArtificial SequenceDyad patterns over-represented in STAR elements 796cagnnnnnnn nnnnnnnngc g 2179724DNAArtificial SequenceDyad patterns over-represented in STAR elements 797cccnnnnnnn nnnnnnnnnn ngtc 247989DNAArtificial SequenceDyad patterns over-represented in STAR elements 798gcgnnnccc 979917DNAArtificial SequenceDyad patterns over-represented in STAR elements 799cggnnnnnnn nnnngcc 178007DNAArtificial SequenceDyad patterns over-represented in STAR elements 800cccncgg 780110DNAArtificial SequenceDyad patterns over-represented in STAR elements 801gccnnnncca 1080210DNAArtificial SequenceDyad patterns over-represented in STAR elements 802cccnnnnccg 108038DNAArtificial SequenceDyad patterns over-represented in STAR elements 803cgtnngca 880413DNAArtificial SequenceDyad patterns over-represented in STAR elements 804agcnnnnnnn tcg 1380521DNAArtificial SequenceDyad patterns over-represented in STAR elements 805ccgnnnnnnn nnnnnnnnga a 2180611DNAArtificial SequenceDyad patterns over-represented in STAR elements 806accnnnnncc c 1180720DNAArtificial SequenceDyad patterns over-represented in STAR elements 807cgcnnnnnnn nnnnnnngag 2080813DNAArtificial SequenceDyad patterns over-represented in STAR elements 808cccnnnnnnn cgc 1380918DNAArtificial SequenceDyad patterns over-represented in STAR elements 809gagnnnnnnn nnnnncgc 1881023DNAArtificial SequenceDyad patterns over-represented in STAR elements 810ggcnnnnnnn nnnnnnnnnn ccc 2381117DNAArtificial SequenceDyad patterns over-represented in STAR elements 811acgnnnnnnn nnnnctc 1781215DNAArtificial SequenceDyad patterns over-represented in STAR elements 812acannnnnnn nncgg 1581313DNAArtificial SequenceDyad patterns over-represented in STAR elements 813ctgnnnnnnn ccc 138148DNAArtificial SequenceDyad patterns over-represented in STAR elements 814cccnngcc 88158DNAArtificial SequenceDyad patterns over-represented in STAR elements 815cggnngca 88166DNAArtificial SequenceDyad patterns over-represented in STAR elements 816ccctgc 681713DNAArtificial SequenceDyad patterns over-represented in STAR elements 817cgcnnnnnnn acc 138188DNAArtificial SequenceDyad patterns over-represented in STAR elements 818gcanngcc 881914DNAArtificial SequenceDyad patterns over-represented in STAR elements 819gcgnnnnnnn ncca 148206DNAArtificial SequenceDyad patterns over-represented in STAR elements 820agccgc 68218DNAArtificial SequenceDyad patterns over-represented in STAR elements 821gcgnngca 88228DNAArtificial SequenceDyad patterns over-represented in STAR elements 822ccgnngtc 88239DNAArtificial SequenceDyad patterns over-represented in STAR elements 823ccgnnnaca 982419DNAArtificial SequenceDyad patterns over-represented in STAR elements 824acgnnnnnnn nnnnnntgg 1982514DNAArtificial SequenceDyad patterns over-represented in STAR elements 825ccannnnnnn ncgc 1482615DNAArtificial SequenceDyad patterns over-represented in STAR elements 826ccgnnnnnnn nnggc 1582711DNAArtificial SequenceDyad patterns over-represented in STAR elements 827ccannnnncc g 118289DNAArtificial SequenceDyad patterns over-represented in STAR elements 828aggnnnggg 98298DNAArtificial SequenceDyad patterns over-represented in STAR elements 829cagnnggc 883014DNAArtificial SequenceDyad patterns over-represented in STAR elements 830cccnnnnnnn ncag 1483111DNAArtificial SequenceDyad patterns over-represented in STAR elements 831agcnnnnnca g 1183222DNAArtificial SequenceDyad patterns over-represented in STAR elements 832cggnnnnnnn nnnnnnnnng cc 2283321DNAArtificial SequenceDyad patterns over-represented in STAR elements 833gcgnnnnnnn nnnnnnnncc c 2183417DNAArtificial SequenceDyad patterns over-represented in STAR elements 834cccnnnnnnn nnnngcc 178358DNAArtificial SequenceDyad patterns over-represented in STAR elements 835cgannacg 883610DNAArtificial SequenceDyad patterns over-represented in STAR elements 836cggnnnngcc 1083712DNAArtificial SequenceDyad patterns over-represented in STAR elements 837cacnnnnnnc gc 1283811DNAArtificial SequenceDyad patterns over-represented in STAR elements 838cggnnnnnac g 1183910DNAArtificial SequenceDyad patterns over-represented in STAR elements 839ctgnnnngcc 1084024DNAArtificial SequenceDyad patterns over-represented in STAR elements 840gggnnnnnnn nnnnnnnnnn ncga 2484114DNAArtificial SequenceDyad patterns over-represented in STAR elements 841cctnnnnnnn ncgc 1484210DNAArtificial SequenceDyad patterns over-represented in STAR elements 842gccnnnnccc 1084316DNAArtificial SequenceDyad patterns over-represented in STAR elements 843cggnnnnnnn nnngcc 1684411DNAArtificial SequenceDyad patterns over-represented in STAR elements 844gccnnnnngg a 1184513DNAArtificial SequenceDyad patterns over-represented in STAR elements 845accnnnnnnn gcg 1384614DNAArtificial SequenceDyad patterns over-represented in STAR elements 846cccnnnnnnn ncgc 1484711DNAArtificial SequenceDyad patterns over-represented in STAR elements 847cagnnnnncc c 1184820DNAArtificial SequenceDyad patterns over-represented in STAR elements 848cacnnnnnnn nnnnnnngga 208497DNAArtificial SequenceDyad patterns over-represented in STAR elements 849cccngcc 785011DNAArtificial SequenceDyad patterns over-represented in STAR elements 850cccnnnnnag c 1185111DNAArtificial SequenceDyad patterns over-represented in STAR elements 851ggcnnnnngg a 1185223DNAArtificial SequenceDyad patterns over-represented in STAR elements 852cgannnnnnn nnnnnnnnnn gag 2385313DNAArtificial SequenceDyad patterns over-represented in STAR elements 853cgcnnnnnnn aca 1385419DNAArtificial SequenceDyad patterns over-represented in STAR elements 854ccannnnnnn nnnnnnccc 1985526DNAArtificial SequenceDyad patterns over-represented in STAR elements 855cggnnnnnnn nnnnnnnnnn nnnggc 2685623DNAArtificial SequenceDyad patterns over-represented in STAR elements 856cccnnnnnnn nnnnnnnnnn gcc 2385716DNAArtificial SequenceDyad patterns over-represented in STAR elements 857cctnnnnnnn nnnccg 1685814DNAArtificial SequenceDyad patterns over-represented in STAR elements 858cccnnnnnnn nccg 148599DNAArtificial SequenceDyad patterns over-represented in STAR elements 859cgcnnngag 986013DNAArtificial SequenceDyad patterns over-represented in STAR elements 860cgcnnnnnnn aag 1386117DNAArtificial SequenceDyad patterns over-represented in STAR elements 861cggnnnnnnn nnnngga 1786221DNAArtificial SequenceDyad patterns over-represented in STAR elements 862ccgnnnnnnn nnnnnnnncc g 218639DNAArtificial SequenceDyad patterns over-represented in STAR elements 863cccnnngca 98648DNAArtificial SequenceDyad patterns over-represented in STAR elements 864cggnncag 88658DNAArtificial SequenceDyad patterns over-represented in STAR elements 865aggnnccg 886610DNAArtificial SequenceDyad patterns over-represented in STAR elements 866cccnnnncac 1086725DNAArtificial SequenceDyad patterns over-represented in STAR elements 867ggannnnnnn nnnnnnnnnn nnccc 2586814DNAArtificial SequenceDyad patterns over-represented in STAR elements 868cccnnnnnnn ncac 1486912DNAArtificial SequenceDyad patterns over-represented in STAR elements 869accnnnnnnc cg

1287012DNAArtificial SequenceDyad patterns over-represented in STAR elements 870cccnnnnnng gc 1287112DNAArtificial SequenceDyad patterns over-represented in STAR elements 871cccnnnnnnc cg 1287220DNAArtificial SequenceDyad patterns over-represented in STAR elements 872cgcnnnnnnn nnnnnnngcc 2087311DNAArtificial SequenceDyad patterns over-represented in STAR elements 873ccgnnnnntc c 1187412DNAArtificial SequenceDyad patterns over-represented in STAR elements 874gccnnnnnng cc 1287513DNAArtificial SequenceDyad patterns over-represented in STAR elements 875cggnnnnnnn gga 1387612DNAArtificial SequenceDyad patterns over-represented in STAR elements 876gggnnnnnng ga 1287718DNAArtificial SequenceDyad patterns over-represented in STAR elements 877gccnnnnnnn nnnnntcc 1887822DNAArtificial SequenceDyad patterns over-represented in STAR elements 878agtnnnnnnn nnnnnnnnnc cg 2287925DNAArtificial SequenceDyad patterns over-represented in STAR elements 879ggcnnnnnnn nnnnnnnnnn nngcc 258809DNAArtificial SequenceDyad patterns over-represented in STAR elements 880ccgnnnccg 988114DNAArtificial SequenceDyad patterns over-represented in STAR elements 881cccnnnnnnn nacc 1488221DNAArtificial SequenceDyad patterns over-represented in STAR elements 882cagnnnnnnn nnnnnnnngc c 2188323DNAArtificial SequenceDyad patterns over-represented in STAR elements 883cccnnnnnnn nnnnnnnnnn cgg 238847DNAArtificial SequenceDyad patterns over-represented in STAR elements 884gcgncca 788520DNAArtificial SequenceDyad patterns over-represented in STAR elements 885cccnnnnnnn nnnnnnncag 2088614DNAArtificial SequenceDyad patterns over-represented in STAR elements 886cccnnnnnnn nccc 1488718DNAArtificial SequenceDyad patterns over-represented in STAR elements 887acannnnnnn nnnnngcg 1888810DNAArtificial SequenceDyad patterns over-represented in STAR elements 888aggnnnnccg 1088919DNAArtificial SequenceDyad patterns over-represented in STAR elements 889cgcnnnnnnn nnnnnngcc 198908DNAArtificial SequenceDyad patterns over-represented in STAR elements 890gagnncgc 889115DNAArtificial SequenceDyad patterns over-represented in STAR elements 891cccnnnnnnn nngcg 1589223DNAArtificial SequenceDyad patterns over-represented in STAR elements 892cgcnnnnnnn nnnnnnnnnn aca 2389323DNAArtificial SequenceDyad patterns over-represented in STAR elements 893gcgnnnnnnn nnnnnnnnnn cca 2389424DNAArtificial SequenceDyad patterns over-represented in STAR elements 894aagnnnnnnn nnnnnnnnnn nccg 248957DNAArtificial SequenceDyad patterns over-represented in STAR elements 895cgcngga 78967DNAArtificial SequenceDyad patterns over-represented in STAR elements 896ccanccc 789724DNAArtificial SequenceDyad patterns over-represented in STAR elements 897cgtnnnnnnn nnnnnnnnnn ntgc 2489820DNAArtificial SequenceDyad patterns over-represented in STAR elements 898tccnnnnnnn nnnnnnncga 2089911DNAArtificial SequenceDyad patterns over-represented in STAR elements 899cacnnnnngg g 1190018DNAArtificial SequenceDyad patterns over-represented in STAR elements 900ccgnnnnnnn nnnnngca 1890112DNAArtificial SequenceDyad patterns over-represented in STAR elements 901ctgnnnnnnc cc 1290214DNAArtificial SequenceDyad patterns over-represented in STAR elements 902cggnnnnnnn nggc 1490317DNAArtificial SequenceDyad patterns over-represented in STAR elements 903ccannnnnnn nnnnggg 1790425DNAArtificial SequenceDyad patterns over-represented in STAR elements 904acgnnnnnnn nnnnnnnnnn nncaa 2590526DNAArtificial SequenceDyad patterns over-represented in STAR elements 905gggnnnnnnn nnnnnnnnnn nnnccc 2690610DNAArtificial SequenceDyad patterns over-represented in STAR elements 906cgcnnnncag 1090723DNAArtificial SequenceDyad patterns over-represented in STAR elements 907agcnnnnnnn nnnnnnnnnn ggg 2390826DNAArtificial SequenceDyad patterns over-represented in STAR elements 908cacnnnnnnn nnnnnnnnnn nnnccg 2690923DNAArtificial SequenceDyad patterns over-represented in STAR elements 909acgnnnnnnn nnnnnnnnnn cag 239107DNAArtificial SequenceDyad patterns over-represented in STAR elements 910aggnccc 791118DNAArtificial SequenceDyad patterns over-represented in STAR elements 911cgtnnnnnnn nnnnncac 1891215DNAArtificial SequenceDyad patterns over-represented in STAR elements 912cggnnnnnnn nnggc 1591316DNAArtificial SequenceDyad patterns over-represented in STAR elements 913cgcnnnnnnn nnngcg 1691412DNAArtificial SequenceDyad patterns over-represented in STAR elements 914cccnnnnnnc tc 1291516DNAArtificial SequenceDyad patterns over-represented in STAR elements 915ccgnnnnnnn nnnagg 1691624DNAArtificial SequenceDyad patterns over-represented in STAR elements 916cccnnnnnnn nnnnnnnnnn ncag 2491723DNAArtificial SequenceDyad patterns over-represented in STAR elements 917agcnnnnnnn nnnnnnnnnn ccg 2391815DNAArtificial SequenceDyad patterns over-represented in STAR elements 918agcnnnnnnn nngcg 159199DNAArtificial SequenceDyad patterns over-represented in STAR elements 919ccannnggc 992017DNAArtificial SequenceDyad patterns over-represented in STAR elements 920cccnnnnnnn nnnnggc 1792111DNAArtificial SequenceDyad patterns over-represented in STAR elements 921acgnnnnngc a 1192220DNAArtificial SequenceDyad patterns over-represented in STAR elements 922cccnnnnnnn nnnnnnncgg 2092311DNAArtificial SequenceDyad patterns over-represented in STAR elements 923cccnnnnncc a 119247DNAArtificial SequenceDyad patterns over-represented in STAR elements 924ccgnagg 792516DNAArtificial SequenceDyad patterns over-represented in STAR elements 925gggnnnnnnn nnngac 1692621DNAArtificial SequenceDyad patterns over-represented in STAR elements 926cgcnnnnnnn nnnnnnnncc a 2192725DNAArtificial SequenceDyad patterns over-represented in STAR elements 927cctnnnnnnn nnnnnnnnnn nncgc 259289DNAArtificial SequenceDyad patterns over-represented in STAR elements 928cgtnnncgc 992920DNAArtificial SequenceDyad patterns over-represented in STAR elements 929agcnnnnnnn nnnnnnnccg 209308DNAArtificial SequenceDyad patterns over-represented in STAR elements 930ggcnncga 893114DNAArtificial SequenceDyad patterns over-represented in STAR elements 931cagnnnnnnn nccc 149328DNAArtificial SequenceDyad patterns over-represented in STAR elements 932ccgnngac 893325DNAArtificial SequenceDyad patterns over-represented in STAR elements 933agcnnnnnnn nnnnnnnnnn nnagg 2593410DNAArtificial SequenceDyad patterns over-represented in STAR elements 934cctnnnnggc 1093517DNAArtificial SequenceDyad patterns over-represented in STAR elements 935ccgnnnnnnn nnnnagc 1793610DNAArtificial SequenceDyad patterns over-represented in STAR elements 936cacnnnncgc 109377DNAArtificial SequenceDyad patterns over-represented in STAR elements 937ccgnccc 793819DNAArtificial SequenceDyad patterns over-represented in STAR elements 938ctgnnnnnnn nnnnnnggc 1993922DNAArtificial SequenceDyad patterns over-represented in STAR elements 939cgcnnnnnnn nnnnnnnnna cc 2294024DNAArtificial SequenceDyad patterns over-represented in STAR elements 940cacnnnnnnn nnnnnnnnnn ncag 2494114DNAArtificial SequenceDyad patterns over-represented in STAR elements 941ggcnnnnnnn ngcc 1494221DNAArtificial SequenceDyad patterns over-represented in STAR elements 942gggnnnnnnn nnnnnnnngg a 2194322DNAArtificial SequenceDyad patterns over-represented in STAR elements 943ccgnnnnnnn nnnnnnnnng cc 2294426DNAArtificial SequenceDyad patterns over-represented in STAR elements 944ccgnnnnnnn nnnnnnnnnn nnnacc 2694513DNAArtificial SequenceDyad patterns over-represented in STAR elements 945cgannnnnnn ccc 1394612DNAArtificial SequenceDyad patterns over-represented in STAR elements 946ccgnnnnnnc tc 1294716DNAArtificial SequenceDyad patterns over-represented in STAR elements 947cggnnnnnnn nnnctc 1694822DNAArtificial SequenceDyad patterns over-represented in STAR elements 948cagnnnnnnn nnnnnnnnnc gc 229499DNAArtificial SequenceDyad patterns over-represented in STAR elements 949ccannnagg 995024DNAArtificial SequenceDyad patterns over-represented in STAR elements 950gccnnnnnnn nnnnnnnnnn ngcc 2495124DNAArtificial SequenceDyad patterns over-represented in STAR elements 951cgcnnnnnnn nnnnnnnnnn ngga 2495226DNAArtificial SequenceDyad patterns over-represented in STAR elements 952ccgnnnnnnn nnnnnnnnnn nnnggc 2695316DNAArtificial SequenceDyad patterns over-represented in STAR elements 953acannnnnnn nnngcg 1695411DNAArtificial SequenceDyad patterns over-represented in STAR elements 954cggnnnnncc c 1195513DNAArtificial SequenceDyad patterns over-represented in STAR elements 955cccnnnnnnn tcc 1395616DNAArtificial SequenceDyad patterns over-represented in STAR elements 956acgnnnnnnn nnncgc 169579DNAArtificial SequenceDyad patterns over-represented in STAR elements 957cccnnntcc 995814DNAArtificial SequenceDyad patterns over-represented in STAR elements 958ccgnnnnnnn ncgg 1495921DNAArtificial SequenceDyad patterns over-represented in STAR elements 959ccannnnnnn nnnnnnnncg g 2196012DNAArtificial SequenceDyad patterns over-represented in STAR elements 960ccgnnnnnnc cg 129619DNAArtificial SequenceDyad patterns over-represented in STAR elements 961cagnnngcg 99627DNAArtificial SequenceDyad patterns over-represented in STAR elements 962gagnccc 796324DNAArtificial SequenceDyad patterns over-represented in STAR elements 963ccgnnnnnnn nnnnnnnnnn ntgc 2496413DNAArtificial SequenceDyad patterns over-represented in STAR elements 964cccnnnnnnn cca 139659DNAArtificial SequenceDyad patterns over-represented in STAR elements 965cggnnncca 99667DNAArtificial SequenceDyad patterns over-represented in STAR elements 966acgnccc 796719DNAArtificial SequenceDyad patterns over-represented in STAR elements 967cggnnnnnnn nnnnnntga 1996812DNAArtificial SequenceDyad patterns over-represented in STAR elements 968ctcnnnnnng gc 129698DNAArtificial SequenceDyad patterns over-represented in STAR elements 969gcgnngac 897017DNAArtificial SequenceDyad patterns over-represented in STAR elements 970gggnnnnnnn nnnnacc 1797110DNAArtificial SequenceDyad patterns over-represented in STAR elements 971cgcnnnngga 1097217DNAArtificial SequenceDyad patterns over-represented in STAR elements 972cccnnnnnnn nnnnccg 1797325DNAArtificial SequenceDyad patterns over-represented in STAR elements 973ccgnnnnnnn nnnnnnnnnn nngca 259746DNAArtificial SequenceDyad patterns over-represented in STAR elements 974gcggca 697513DNAArtificial SequenceDyad patterns over-represented in STAR elements 975agannnnnnn ccc 139768DNAArtificial SequenceDyad patterns over-represented in STAR elements 976cggnncca 897712DNAArtificial SequenceDyad patterns over-represented in STAR elements 977cccnnnnnnc cc 1297810DNAArtificial SequenceDyad patterns over-represented in STAR elements 978accnnnngcg 1097921DNAArtificial SequenceDyad patterns over-represented in STAR elements 979cctnnnnnnn nnnnnnnncg c 2198015DNAArtificial SequenceDyad patterns over-represented in STAR elements 980agcnnnnnnn nngtc 1598124DNAArtificial SequenceDyad patterns over-represented in STAR elements 981cccnnnnnnn nnnnnnnnnn nctc 2498224DNAArtificial SequenceDyad patterns over-represented in STAR elements 982cgcnnnnnnn nnnnnnnnnn ncga 2498321DNAArtificial SequenceDyad patterns over-represented in STAR elements 983cccnnnnnnn nnnnnnnngc c 2198417DNAArtificial SequenceDyad patterns over-represented in STAR elements 984accnnnnnnn nnnnggc 1798521DNAArtificial SequenceDyad patterns over-represented in STAR elements 985aggnnnnnnn nnnnnnnncg c

219866DNAArtificial SequenceDyad patterns over-represented in STAR elements 986gcgcca 698715DNAArtificial SequenceDyad patterns over-represented in STAR elements 987gcgnnnnnnn nnagc 1598824DNAArtificial SequenceDyad patterns over-represented in STAR elements 988gggnnnnnnn nnnnnnnnnn ngca 2498923DNAArtificial SequenceDyad patterns over-represented in STAR elements 989cccnnnnnnn nnnnnnnnnn cag 2399014DNAArtificial SequenceDyad patterns over-represented in STAR elements 990ccannnnnnn ncgg 1499116DNAArtificial SequenceDyad patterns over-represented in STAR elements 991ccgnnnnnnn nnnggc 169926DNAArtificial SequenceDyad patterns over-represented in STAR elements 992gcagcc 69938DNAArtificial SequenceDyad patterns over-represented in STAR elements 993cagnncgc 899414DNAArtificial SequenceDyad patterns over-represented in STAR elements 994cgcnnnnnnn nggc 1499523DNAArtificial SequenceDyad patterns over-represented in STAR elements 995ctgnnnnnnn nnnnnnnnnn ggc 2399620DNAArtificial SequenceDyad patterns over-represented in STAR elements 996gggnnnnnnn nnnnnnnacc 209977DNAArtificial SequenceDyad patterns over-represented in STAR elements 997ccgntgc 799814DNAArtificial SequenceDyad patterns over-represented in STAR elements 998cagnnnnnnn ncgc 1499917DNAArtificial SequenceDyad patterns over-represented in STAR elements 999aagnnnnnnn nnnncgc 17100012DNAArtificial SequenceDyad patterns over-represented in STAR elements 1000ccgnnnnnnt cc 12100124DNAArtificial SequenceDyad patterns over-represented in STAR elements 1001ccannnnnnn nnnnnnnnnn nccc 2410026DNAArtificial SequenceDyad patterns over-represented in STAR elements 1002ccaccc 6100312DNAArtificial SequenceDyad patterns over-represented in STAR elements 1003gagnnnnnnc cc 12100426DNAArtificial SequenceDyad patterns over-represented in STAR elements 1004agcnnnnnnn nnnnnnnnnn nnnggc 2610056DNAArtificial SequenceDyad patterns over-represented in STAR elements 1005cagcgc 6100618DNAArtificial SequenceDyad patterns over-represented in STAR elements 1006ccgnnnnnnn nnnnnctc 18100721DNAArtificial SequenceDyad patterns over-represented in STAR elements 1007cgcnnnnnnn nnnnnnnnac g 21100823DNAArtificial SequenceDyad patterns over-represented in STAR elements 1008ggcnnnnnnn nnnnnnnnnn cga 23100922DNAArtificial SequenceDyad patterns over-represented in STAR elements 1009ccgnnnnnnn nnnnnnnnna ag 22101020DNAArtificial SequenceDyad patterns over-represented in STAR elements 1010cgcnnnnnnn nnnnnnntcc 20101113DNAArtificial SequenceDyad patterns over-represented in STAR elements 1011aggnnnnnnn cgc 13101213DNAArtificial SequenceDyad patterns over-represented in STAR elements 1012cggnnnnnnn ccc 13101310DNAArtificial SequenceDyad patterns over-represented in STAR elements 1013cgcnnnngcc 10101412DNAArtificial SequenceDyad patterns over-represented in STAR elements 1014cgannnnnnc cc 12101525DNAArtificial SequenceDyad patterns over-represented in STAR elements 1015cccnnnnnnn nnnnnnnnnn nngga 25101622DNAArtificial SequenceDyad patterns over-represented in STAR elements 1016cccnnnnnnn nnnnnnnnng cg 22101713DNAArtificial SequenceDyad patterns over-represented in STAR elements 1017ccannnnnnn cgc 13101812DNAArtificial SequenceDyad patterns over-represented in STAR elements 1018cccnnnnnng cc 12101920DNAArtificial SequenceDyad patterns over-represented in STAR elements 1019gccnnnnnnn nnnnnnntcc 20102020DNAArtificial SequenceDyad patterns over-represented in STAR elements 1020aggnnnnnnn nnnnnnngcc 20102117DNAArtificial SequenceDyad patterns over-represented in STAR elements 1021cgcnnnnnnn nnnngcc 1710226DNAArtificial SequenceDyad patterns over-represented in STAR elements 1022tccgca 6102314DNAArtificial SequenceDyad patterns over-represented in STAR elements 1023gcgnnnnnnn nccc 14102417DNAArtificial SequenceDyad patterns over-represented in STAR elements 1024ccannnnnnn nnnngcg 17102510DNAArtificial SequenceDyad patterns over-represented in STAR elements 1025cacnnnnggg 10102613DNAArtificial SequenceDyad patterns over-represented in STAR elements 1026cggnnnnnnn tcc 13102711DNAArtificial SequenceDyad patterns over-represented in STAR elements 1027gcgnnnnngc c 11102818DNAArtificial SequenceDyad patterns over-represented in STAR elements 1028acgnnnnnnn nnnnncag 18102925DNAArtificial SequenceDyad patterns over-represented in STAR elements 1029ccgnnnnnnn nnnnnnnnnn nncgc 25103014DNAArtificial SequenceDyad patterns over-represented in STAR elements 1030cggnnnnnnn ntgc 1410317DNAArtificial SequenceDyad patterns over-represented in STAR elements 1031cccngag 7103225DNAArtificial SequenceDyad patterns over-represented in STAR elements 1032gcgnnnnnnn nnnnnnnnnn nntga 25103321DNAArtificial SequenceDyad patterns over-represented in STAR elements 1033ggcnnnnnnn nnnnnnnngc c 21103413DNAArtificial SequenceDyad patterns over-represented in STAR elements 1034ccgnnnnnnn ccc 13103525DNAArtificial SequenceDyad patterns over-represented in STAR elements 1035acannnnnnn nnnnnnnnnn nnccc 25103622DNAArtificial SequenceDyad patterns over-represented in STAR elements 1036accnnnnnnn nnnnnnnnng gg 2210377DNAArtificial SequenceDyad patterns over-represented in STAR elements 1037aganggc 7103823DNAArtificial SequenceDyad patterns over-represented in STAR elements 1038gggnnnnnnn nnnnnnnnnn tga 23103911DNAArtificial SequenceDyad patterns over-represented in STAR elements 1039cagnnnnngg g 11104019DNAArtificial SequenceDyad patterns over-represented in STAR elements 1040gccnnnnnnn nnnnnncgc 19104113DNAArtificial SequenceDyad patterns over-represented in STAR elements 1041gcgnnnnnnn gga 13104220DNAArtificial SequenceDyad patterns over-represented in STAR elements 1042cagnnnnnnn nnnnnnncca 20104310DNAArtificial SequenceDyad patterns over-represented in STAR elements 1043ccgnnnngtc 10104419DNAArtificial SequenceDyad patterns over-represented in STAR elements 1044cccnnnnnnn nnnnnncgc 19104520DNAArtificial SequenceDyad patterns over-represented in STAR elements 1045gcgnnnnnnn nnnnnnnacc 20104626DNAArtificial SequenceDyad patterns over-represented in STAR elements 1046cagnnnnnnn nnnnnnnnnn nnnggg 26104710DNAArtificial SequenceDyad patterns over-represented in STAR elements 1047ccgnnnnccc 10104811DNAArtificial SequenceDyad patterns over-represented in STAR elements 1048cgcnnnnngg c 11104912DNAArtificial SequenceDyad patterns over-represented in STAR elements 1049cctnnnnnng gc 1210509DNAArtificial SequenceDyad patterns over-represented in STAR elements 1050aggnnnggc 9105117DNAArtificial SequenceDyad patterns over-represented in STAR elements 1051cggnnnnnnn nnnncgc 17105224DNAArtificial SequenceDyad patterns over-represented in STAR elements 1052ctgnnnnnnn nnnnnnnnnn ngga 24105323DNAArtificial SequenceDyad patterns over-represented in STAR elements 1053cacnnnnnnn nnnnnnnnnn cca 2310549DNAArtificial SequenceDyad patterns over-represented in STAR elements 1054cggnnngag 9105515DNAArtificial SequenceDyad patterns over-represented in STAR elements 1055cccnnnnnnn nncca 1510567DNAArtificial SequenceDyad patterns over-represented in STAR elements 1056cccnacg 710577DNAArtificial SequenceDyad patterns over-represented in STAR elements 1057cagngcc 7105812DNAArtificial SequenceDyad patterns over-represented in STAR elements 1058aggnnnnnnc cg 12105915DNAArtificial SequenceDyad patterns over-represented in STAR elements 1059agcnnnnnnn nnggg 15106013DNAArtificial SequenceDyad patterns over-represented in STAR elements 1060cccnnnnnnn ggc 13106119DNAArtificial SequenceDyad patterns over-represented in STAR elements 1061cctnnnnnnn nnnnnnccc 19106225DNAArtificial SequenceDyad patterns over-represented in STAR elements 1062ccgnnnnnnn nnnnnnnnnn nnttc 25106313DNAArtificial SequenceDyad patterns over-represented in STAR elements 1063cccnnnnnnn ccg 13106412DNAArtificial SequenceDyad patterns over-represented in STAR elements 1064cgannnnnng gc 12106510DNAArtificial SequenceDyad patterns over-represented in STAR elements 1065cggnnnnctc 1010666DNAArtificial SequenceDyad patterns over-represented in STAR elements 1066cggcgc 6106719DNAArtificial SequenceDyad patterns over-represented in STAR elements 1067cctnnnnnnn nnnnnnacg 19106812DNAArtificial SequenceDyad patterns over-represented in STAR elements 1068gggnnnnnnc ac 12106922DNAArtificial SequenceDyad patterns over-represented in STAR elements 1069cccnnnnnnn nnnnnnnnnc gc 22107016DNAArtificial SequenceDyad patterns over-represented in STAR elements 1070cccnnnnnnn nnnctc 1610716DNAArtificial SequenceDyad patterns over-represented in STAR elements 1071ccccag 6107211DNAArtificial SequenceDyad patterns over-represented in STAR elements 1072gccnnnnncc c 11

Claims

1. A method for producing a proteinaceous molecule in a cell, the method comprising:providing a cell selected from the group consisting of a cell having an adenovirus Early Region 1 (E1) sequence, a HuNS-1 myeloma cell, a 293 cell, a CHO cell, a Vero cell, a WERI-Rb-1 retinoblastoma cell, a BHK cell, a non-secreting mouse myeloma Sp2/0-Ag 14 cell, a non-secreting mouse myeloma NSO cell, and an NCI-H295R adrenal gland carcinoma cell;wherein the cell comprises an anti-repressor activity sequence operably linked to a nucleic acid sequence encoding a heterologous proteinaceous molecule, wherein the anti-repressor activity sequence comprises SEQ ID NO: 17;expressing the proteinaceous molecule in the cell; andharvesting material comprising the thus expressed proteinaceous molecule.

2. The method according to claim 1, wherein the anti-repressor activity sequence consists of SEQ ID NO: 17.

3. The method according to claim 1, wherein the cell comprises an adenovirus Early Region 1 (E1) sequence.

4. The method according to claim 1, wherein the proteinaceous molecule is secreted by the cell.

5. The method according to claim 2, wherein the proteinaceous molecule is secreted by the cell.

6. The method according to claim 1, wherein the cell comprises a plurality of said anti-repressor activity sequence operably linked to the nucleic acid sequence encoding the heterologous proteinaceous molecule.

7. The method according to claim 6, wherein at least one anti-repressor activity sequence is positioned 5' of the sequence encoding the proteinaceous molecule and at least one anti-repressor activity sequence is positioned 3' of the sequence encoding the proteinaceous molecule.

8. The method according to claim 1, wherein the cell is a CHO cell.

9. The method according to claim 6, wherein the cell is a CHO cell.

10. The method according to claim 7, wherein the cell is a CHO cell.

11. A method for producing a proteinaceous molecule in a cell, the method comprising:providing a cell selected from the group consisting of a cell having an adenovirus Early Region 1 (E1) sequence, a HuNS-1 myeloma cell, a 293 cell, a CHO cell, a Vero cell, a WERI-Rb-1 retinoblastoma cell, a BHK cell, a non-secreting mouse myeloma Sp2/0-Ag 14 cell, a non-secreting mouse myeloma NSO cell, and an NCI-H295R adrenal gland carcinoma cell; wherein the cell comprises an anti-repressor activity sequence operably linked to a nucleic acid sequence encoding a heterologous proteinaceous molecule, wherein the anti-repressor activity sequence comprises at least 50 bases of SEQ ID NO: 17;expressing the proteinaceous molecule in the cell; andharvesting material comprising the thus expressed proteinaceous molecule.

12. A recombinant host cell line comprising:a cell selected from the group consisting of a cell line comprising an adenovirus Early Region 1 (E1) sequence, a HuNS-1 myeloma cell line, a 293 cell line, a CHO cell line, a Vero cell line, a WERI-Rb-1 retinoblastoma cell line, a BHK cell line, a non-secreting mouse myeloma Sp2/0-Ag 14 cell line, a non-secreting mouse myeloma NSO cell line, and an NCI-H295R adrenal gland carcinoma cell line;the cell comprising an anti-repressor activity sequence operably linked to a nucleic acid sequence encoding a heterologous proteinaceous molecule, wherein the anti-repressor activity sequence comprises SEQ ID NO: 17.

13. The cell line of claim 12, wherein the anti-repressor activity sequence consists of SEQ ID NO: 17.

14. The cell line of claim 12, wherein the cell line comprises an adenovirus Early Region 1 sequence.

15. The cell line of claim 12, wherein the cell comprises a plurality of the anti-repressor activity sequence operably linked to said nucleic acid sequence encoding the heterologous proteinaceous molecule.

16. The cell line of claim 12, wherein at least one anti-repressor activity sequence is positioned 5' of the sequence encoding the proteinaceous molecule and at least one anti-repressor activity sequence is positioned 3' of the sequence encoding the proteinaceous molecule.

17. The cell line of claim 12, wherein the cell line is a CHO cell line.

18. The cell line of claim 15, wherein the cell line is a CHO cell line.

19. The cell line of claim 16, wherein the cell line is a CHO cell line.

20. A recombinant host cell line comprising:a cell selected from the group consisting of a cell line comprising an adenovirus Early Region 1 (E1) sequence, a HuNS-1 myeloma cell line, a 293 cell line, a CHO cell line, a Vero cell line, a WERI-Rb-1 retinoblastoma cell line, a BHK cell line, a non-secreting mouse myeloma Sp2/0-Ag 14 cell line, a non-secreting mouse myeloma NSO cell line, and an NCI-H295R adrenal gland carcinoma cell line;wherein the cell comprises an anti-repressor activity sequence operably linked to a nucleic acid sequence encoding a heterologous proteinaceous molecule, wherein the anti-repressor activity sequence comprises at least 50 bases of SEQ ID NO: 17.

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