Methods and Compositions of Nucleic Acid Ligands for Detection of Clinical Analytes Related to Human Health

Abstract

Specific DNA sequences for binding various clinically relevant analytes from the human body are described. Each of these sequences or their linear, two- and three-dimensional linked sequences can function in varying assay and sensor formats with varying degrees of success. Linkage of the whole or partial DNA sequences (putative binding sites) can be used to enhance specificity and affinity towards complex targets, thereby improving assay selectivity and sensitivity in many instances. In addition, a FRET-based quantitative method is described for normalizing analyte data by assessing urine creatinine and urea levels. Finally, a method is described for removing creatinine or urea by size-exclusion chromatography prior to a FRET-based aptamer assay to avoid the denaturing effects of these compounds.

Description

CLAIM OF PRIORITY TO PRIOR APPLICATION

[0001] This application claims the benefit of the filing date of U.S. Provisional Application Ser. No. 61/402,491, filed on Aug. 31, 2010; U.S. Provisional Application Ser. No. 61/463,020, filed on Feb. 10, 2011; and U.S. Non-Provisional application Ser. No. 13/199,484, filed on Aug. 31, 2011, each of which is entitled "Methods and Compositions of Nucleic Acid Ligands for Detection of Clinical Analytes Related to Human Health", the entire disclosures of which are hereby incorporated by reference into the present disclosure, to include the Sequence Listing(s) previously submitted with the subject applications.

BACKGROUND OF THE INVENTION

[0002] 1. Field of the Invention

[0003] The present invention pertains to the field of aptamer- and nucleic acid ligand (DNA and RNA ligand)-based diagnostics. More specifically, the application relates to single-stranded deoxyribonucleic acid ("DNA") and ribonucleic acid ("RNA") ligand sequences, whether individual or linked together to form longer multiple binding site "receptors," that specifically target and bind to clinically relevant analytes on one or more binding sites or "epitopes" from humans such as cardiovascular biomarkers, bone metabolism markers, glucose, natural or recombinant human growth hormone ("hGH" or somatotropin) and vitamins. The invention includes general DNA ligand or aptamer-based detection and quantitation of these analytes in body fluids such as blood plasma, serum, sputum or saliva, interstitial, synovial, or cerebrospinal fluid aspirates, mucus, and urine or solid biopsy samples.

[0004] 2. Background Information

[0005] These individual or linked DNA ligand (aptamer) sequences represent valuable target analyte-responsive components of diagnostic devices or biosensors. A "biosensor" is defined as any device that employs a biologically-derived molecule as the sensing component and transduces a target analyte binding event into a detectable physical signal (including, but not limited to, changes in light intensity, absorbance, transmittance, refraction (Surface Plasmon Resonance or "SPR"), wavelength, color, agglutination of cells or particles, fluorescence intensity, fluorescence lifetime, fluorescence polarization or anisotropy, fluorescence correlation spectroscopy ("FCS"), fluorescence or Forster resonance energy transfer ("FRET"; nonradiative dipole-dipole coupling of fluorophores or fluorophores and quenchers), upconverting phosphor, two-photon interaction phenomena, Raman spectroscopy or surface-enhanced Raman spectroscopy ("SERS"), electrical conduction, electrical resistance or other electrical properties, mass, photon or radioactive particle emissions, etc).

[0006] Once bonded with the target, these DNA ligand sequences can be used to qualitatively determine the presence of analyte, as well as to quantify or semi-quantify the target analyte amount in a sample using a broad variety of assay types and diagnostic or sensor platforms including, but not limited to, affinity-based lateral flow test strips, membrane blotting, SPR, surface acoustic waveguides ("SAW" devices), magnetic bead ("MB")-based capture, plastic-adherent sandwich assays ("PASA"), chemiluminescence ("CL"), electrochemiluminescence ("ECL"), radioisotopic, fluorescence intensity, including quantum dot ("QD") or other fluorescent nanoparticle ("FNP") of dye-based, fluorescence lifetime, and fluorescence polarization ("FP") assays or enzyme-linked ("ELISA-like") microplate assays. ELISA-like assays refer to microwell or microplate assays similar to traditional Enzyme-Linked Immunosorbent Assays ("ELISA") in which an aptamer or nucleic acid ligand is substituted for the antibody or receptor component or components, but the other components such as peroxidase or alkaline phosphatase enzymes and color-producing substrates remain the same.

[0007] In addition, these DNA ligand sequences are valuable in competitive displacement assays which are not solely dependent on high affinity (strong attractive forces between a receptor and its ligand) or high avidity (high tensile or physical strength of receptor-ligand bonds) to produce sensitive detection (sub-nanoMolar or sub-nanogram levels), because the equilibrium constant (generally K.sub.a=10.sup.6 to 10.sup.8 to enable competition) must allow reasonable displacement of previously bound target materials to detect a change at or below nanogram or nanoMolar levels.

[0008] In a competitive displacement assay, labeled DNA ligand plus labeled analyte complexes compete with unlabeled analyte to bind with the labeled DNA. After allowing the labeled and unlabeled analytes to come to equilibrium with the labeled DNA, the unlabeled target analyte may be quantitatively assayed by fluorescence intensity or other methods. Such assays would include competitive displacement FRET assays or DNA ligand "beacon" FRET assays. In a competitive displacement FRET assay the fluorophore ("F") and quencher ("Q") are placed in a putative binding loop or pocket so as to reside within the Forster distance of 60-85 Angstroms to enable quenching.

[0009] In an aptamer beacon assay, the F and Q labels are placed on the 5' and 3' ends and binding of the target analyte to the beacon opens the beacon beyond the Forster quenching distance so that F is no longer quenched and emits light generally in proportion to the amount of target analyte introduced into the liquid system. Each of these types of aptamer assays and detection platforms has different applications in either central medical laboratories or in point-of-care ("POC") sensor devices for use in emergency rooms, intensive care units, cardiac care units, or physician's offices and clinics.

SUMMARY OF THE INVENTION

[0010] The DNA ligand sequences listed herein (Table 9) were derived by iterative cycles of affinity-based selection, washing, heated elution, and polymerase chain reaction ("PCR") amplification of bound DNA ligands from a randomized library using immobilized target analytes for affinity selection and PCR amplification followed by cloning and Sanger dideoxynucleotide DNA sequencing.

[0011] Sanger dideoxynucleotide sequencing refers to DNA chain termination due to a lack of a 3' hydroxyl (--OH) group to link incoming bases to during DNA synthesis followed by automated fluorescence reading of the DNA sequence from an electrophoresis gel containing all of the terminated DNA fragments. DNA sequencing may be accomplished by PCR doped with dideoxynucleotides lacking hydroxyl groups at the 2' and 3' sugar ring positions and thereby disallowing chain formation. PCR refers to the enzymatic amplification or copying of DNA molecules with a thermo-stable DNA polymerase such as Thermus aquaticus polymerase (Taq) with known "primer" regions or short oligonucleotides of known sequence that can hybridize to a longer target DNA sequence to enable priming of the chain reaction (exponential doubling of the DNA target copy number with each round of amplification).

[0012] A randomized library can be chemically synthesized by linking together the four deoxynucleotide triphosphate bases (adenine; A, cytosine; C, guanine; G, and thymine; T) in equal amounts (25% each), so that a combinatorial oligonucleotide arises with sequence diversity equal to 4 raised to the nth power (4.sup.n) where n is the desired length of the randomized region in bases. In other words, if position 1 in an oligonucleotide is allowed to consist of A, C, G, or T (diversity=4) by equal availability of all 4 bases and these 4 possibilities are multiplied by each base linking to 4 more possible bases at position 2, then this process yields 16 possible 2-base oligonucleotides (i.e., AA, AC, AG, AT, CA, CC, CG, CT, GA, GC, GG, GT, TA, TC, TG, TT) and so on for the entire chosen length (n) of the randomized region. This combinatorial progression displays immense diversity as a function of oligonucleotide chain length. For example, an oligonucleotide decamer of 10 base length could be expected to contain 4.sup.n=4.sup.10 or 1,048,576 unique DNA sequences from which to chose or select one or more DNA sequences that bind a given immobilized target analyte with the strongest affinities.

[0013] The randomized oligonucleotide or DNA is designed to be flanked on either side by short primer regions of known and fixed sequences to enable PCR amplification (exponential copying) of the rare sequences that are selected from the random library by binding to the target after the non-binding members of the random library are washed away (not selected).

[0014] Additional assays, such as ELISA-like plate assays or fluorescence (e.g., intensity and FRET) assays, may be used to screen or verify the value of particular DNA and RNA ligands or aptamer sequences for detection of a given target analyte in a given assay format or type of biosensor. Some of the sequences operate (bind and transduce the binding signal) more effectively in affinity-based (ELISA-like or fluorescence intensity) assays, while other DNA ligand sequences against the same targets function better in lower affinity competitive or other assays, thereby leading to more sensitive detection with lower limits of detection (sub-nanoMolar or sub-nanogram) and less cross-reactivity or more specificity for the target analyte. "Specificity" or "selectivity" means the ability to selectively exclude molecules similar in structure to the true target analyte that may interfere with the assay and give false indications of detection. All of the listed DNA ligand nucleotide sequences have potential applications in some type of assay format, because they have survived at least 5 rounds of affinity-based selection and enrichment (by PCR amplification), although some of the sequences will undoubtedly perform better in certain assay formats or configurations (in tubes, square cuvettes, membranes, or on biochips) than others.

[0015] Combinations of the DNA ligands, whether in whole or in part (i.e., their binding sites of approximately 5-10 or more nucleotides or bases), could be linked together in a linear or 2-dimensional ("2-D") or 3-dimensional ("3-D") fashion similar to dendrimers as shown in FIG. 1B to bind multiple epitopes or binding sites on a complex target analyte (Ag or antigen) such as a virus or whole prokaryotic (bacterial) or eukaryotic (animal, fungal or plant) cell surface having numerous spatially separated epitopes of different types. The advantage of linking aptamers or their shorter binding pockets, loops or binding sites is that the nascent linear, 2-D, or 3-D aptamer construct will likely have improved affinity or "avidity" (tensile binding strength) making it more difficult to remove or dissociate from the target antigen. Higher affinity and avidity generally lead to greater assay sensitivity and specificity which are typically desirable traits in many assays.

[0016] The linked aptamer complex will be likely to gain specificity as well since the probability of binding to multiple epitopes with any degree of success is multiplicative. Thus, the ability to bind to epitopes A, B and C equals the product of the probability of binding to A with high affinity times the probability of binding to B with high affinity times the probability of binding to C with high affinity. The product of those three fractional probabilities is clearly much less than the probability of binding to only A, B, or C independently in the absence of binding the other two or any combination of the two epitopes therein in the absence of binding the third. Hence by linking two or more aptamers or their binding regions with or without DNA or other "spacer" regions, the selectivity or specificity of aptamers or DNA ligands can be increased.

[0017] This approach to binding site linkage emulates the nature of antibodies which demonstrates linkage of their "hypervariable" ("HV") regions on the antigen combining sites of the immunoglobulin ("Ig") light and heavy chains. In the HV regions, the variability of the 20 amino acid types is quite high and essentially represents a selection of one combination from a large combinatorial library in the protein realm (similar to down selection of a few candidate aptamers from a large diverse starting library). The trait of HV region linkage contributes to Ig affinity, avidity and specificity. Similarly, linking aptamers or aptamer binding sites for various epitopes in one, two or three dimensions will enhance larger aptamer or DNA ligand construct affinity, avidity, and selectivity or specificity as illustrated in FIGS. 1A and 1B.

[0018] The present invention provides specific DNA sequence information for nucleic acid ligands (aptamers) or their linked constructs selected from randomized pools to bind clinically important proteins, peptides, hormones, sugars, vitamins, post-translational N-acetylglucosamine (NAG or O-GlcNAc) modifications of key proteins, etc. in a variety of assay formats and sensor or diagnostic platforms for assessment of human health status. While all of the candidate sequences have been shown to bind their cognate targets, some are shown to function more effectively in affinity-based assays versus fluorescence resonance energy transfer (FRET) or other assay formats that rely more on physical parameters other than affinity such as fluorophore-quencher proximity (i.e., the Forster distance). Therefore, all of the sequences are potentially valuable for simple qualitative detection or quantitative assays, but some may function better in terms of sensitive and specific detection than others in particular assay formats.

BRIEF DESCRIPTION OF THE DRAWINGS

[0019] FIG. 1A illustrates an antibody, revealing the multiple hypervariable antigen combining of binding sites on both the heavy and light chains.

[0020] FIG. 1B illustrates the concept of linking aptamers or their binding sites in a linear fashion (although 2-D and 3-D linkages are also possible) to mimic the linkage of multiple hypervariable (HV) regions in antigen combining sites of antibody chains to enhance affinity, avidity, and specificity against complex target antigens (Ag) containing two or more distinct epitopes.

[0021] FIG. 2 represents secondary stem-loop structures of DNA ligands or aptamers (SEQ ID NOs 3 and 4).

[0022] FIGS. 3A-3F show how the aptamer beacons from FIG. 2 behaved as a function of decreasing CTx peptide concentration.

[0023] FIG. 4A illustrates specificity of the 15-base CTx 2R-2h aptamer beacon for the full-length 26-amino acid (AA) version of the CTx peptide.

[0024] FIG. 4B shows the same samples evaluated by a handheld fluorometer that only reports fluorescence peak height, but confirms the level of specificity.

[0025] FIG. 5 shows the relative linearity and sensitivity of the 15-base CTx 2R-2h aptamer beacon assay.

[0026] FIG. 6A illustrates the ability to normalize urine concentration readings with simple aptamer beacon fluorescence readings.

[0027] FIG. 6B shows a quantitative estimation of creatinine and urea levels in urine or serum using the aptamer beacon denaturation approach.

[0028] FIG. 7A illustrates that the 2,942 dalton (26-amino acid) CTx bone peptide can be extracted from urine to avoid the denaturing effects of creatinine and urea on the CTx 2R-2h aptamer beacon assay by use of a desalting size-exclusion polyacrylamide bead column.

[0029] FIG. 7B shows that CTx peptide extracted from human urine by means of a desalting column can still be detected to a level of at least 122 ng/ml by the CTx 2R-2h aptamer beacon.

[0030] FIG. 8 illustrates the secondary stem-loop structures of several aptamers which dominated a sequenced pool of vitamin D3 aptamers (abbreviated VD3 and from the SEQ ID NOs 429-526).

[0031] FIGS. 9A-9D illustrate the FRET responses of loops A, B, and C for the aptamers shown in FIG. 8.

[0032] FIGS. 10A-10C reveal that the VD3 Loop C beacon appears to react equally well with (A) 1-hydroxy-vitamin D2, (B) 1-hydroxy-vitamin D3 and (C) 25-hydroxy-vitamin D3.

[0033] FIG. 11 shows an assessment of the VD3 Loop C beacon.

[0034] FIGS. 12A and 12B summarize assessment of the specificity or cross-reactivity of the VD3 Loop C aptamer beacon versus a variety of potential analytes or interfering species.

[0035] FIGS. 13A and 13B show fluorometric spectra from two separate trials of a competitive displacement FRET assay.

[0036] FIG. 14 shows the same samples from FIG. 13 assessed for fluorescence peak height.

[0037] FIGS. 15A-15D show four examples of aptamers from the pool of aptamers that bind recombinant human growth hormone.

[0038] FIGS. 16A-16D show four more examples of aptamers from the pool of aptamers that bind recombinant human growth hormone.

[0039] FIG. 17A shows an experimental matrix screening scheme for capture aptamer-conjugated magnetic microbeads.

[0040] FIG. 17B shows mean bar heights of three separate measurements.

[0041] FIGS. 18A and 18B give ECL line plots for assay combinations 18 and 40 from the matrix in FIG. 17A.

[0042] FIG. 19A shows an experimental matrix screening scheme for capture aptamer-conjugated magnetic microbeads.

[0043] FIG. 19B shows mean bar heights of three separate measurements.

[0044] FIG. 20A shows the linear ECL response for the sandwich assay of FIG. 19.

[0045] FIG. 20B shows cross-reactivity of the combination number 4 BNP assay versus other peptide or protein analytes that might be found at the 100 ng/ml level in human blood.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0046] There is no single preferred embodiment for use of the DNA aptamer ligand sequences or linked aptamer constructs identified herein. Rather, the sequences are useful to varying extents in a variety of assay formats and sensors or diagnostic devices chosen from at least the following list: lateral flow test strips, Surface Enhanced Raman (SERS), Surface Plasmon Resonance (SPR), Surface Acoustic or Transverse Wave (SAW or STW) detection, electrical, electrochemical, colorimetric absorbance, agglutination, ELISA-like or enzyme-linked microplate assays, magnetic bead-based capture assays, ECL or other chemiluminescence assays, radioisotopic assays and a variety of fluorescence assays including, but not limited to, fluorescence intensity, fluorescence lifetime, fluorescence polarization (FP) and Fluorescence or Forster Resonance Energy Transfer (FRET) assays (both beacon and competitive FRET (Bruno et al., 2010, 2011) in round tubes, square or flat cuvettes, or immobilized on magnetic beads, other types of microbeads, or flat surfaces such as nitrocellulose, nylon, or other membranes or on glass or plastic DNA microarrays or "biochips."

[0047] While there may appear to be considerable variability among sequences that bind the same clinical analyte targets, "epitopes" and their cognate aptamer binding sites are usually quite small (e.g., 5-10 bases) and a single target may contain numerous individual binding sites or epitopes for multiple aptamer binding. In addition, however, there is often a common or consensus sequence (designated herein by slashes between clone numbers in Table 9, e.g. --aptamer clones CTx 2, 13, 19, 20, 25, 32F or R series are identical and only listed once as SEQ ID NO 3 and 4) or common segments of 5-10 or more nucleotides in a row within otherwise different aptamer sequences that can bind a specific target epitope that may dominate the other binding sites by being more physically accessible or having stronger electrostatic, hydrogen bonding, or other attractive forces (summation of van der Waals or other weak forces). Variations in nucleotide sequences around these consensus segments or common binding sequence segments may serve to modulate the binding segment's affinity or specificity or may have no effect at all. These properties must be determined by empirical comparisons.

DNA Ligand (Aptamer) Selection and Generation

[0048] General methods for developing DNA ligands or aptamers to the immobilized proteins, peptides, or small molecules (defined as less than 1,000 daltons) are as follows. The protein, peptide or an amino-derivative of the small molecule (such as glucosamine in the case of D-glucose or dextrose) is then added to 2.times.10.sup.9 tosyl-coated magnetic beads (MBs; e.g., Dynal brand from Invitrogen Corp. Carlsbad, Calif., 2. 8 micron size) for 2 hours at 37.degree. C. The tosyl group is a "leaving" group that allows the formation of a very stable covalent bond between primary amine groups in the target protein, peptide or amino-derivatized small molecule and therefore immobilizes the target on the surfaces of the MBs so that they can be used to probe the randomized DNA library for DNA ligands. Target molecule-conjugated MBs (or target-MBs) are collected for 2 minutes in a magnetic collection device using an external magnet and the supernate is carefully withdrawn with a pipette tip. Target-MBs are then resuspended by vortexing briefly in 1.times. Binding Buffer (1.times.BB; 0.5M NaCl, 10 mM Tris-HCl, and 1 mM MgCl.sub.2, pH 7.5-7.6,) and washed by agitation for 5 minutes. MBs are collected and washed three times in this manner and then resuspended in 1 ml of 1.times.BB.

[0049] MB-based DNA ligand or aptamer development is then performed using a template library sequence such as: 5'-ATCCGTCACACCTGCTCT-N.sub.36-TGGTGTTGGCTCCCGTAT-3', where N.sub.36 represents the randomized 36-base region of the DNA library (maximal sequence diversity=4.sup.36 in theory). Primer sequences are: 5'-ATACGGGAGCCAACACCA-3' (designated forward) and 5'-ATCCGTCACACCTGCTCT-3' (designated reverse) to prime the template and nascent strands for PCR, respectively. The random library is reconstituted in 500 .mu.l of sterile nuclease-free water and heated to 95.degree. C. for 5 minutes to ensure that the DNA library is completely single-stranded and linear. The hot DNA library solution is added to 100 .mu.l of target-MBs (2.times.10.sup.8 beads) with 600 .mu.l of sterile 2.times. Binding Buffer (2.times.BB). The DNA library and target-MB suspension (1.2 ml) is mixed at room temperature (RT, approximately 25.degree. C.) for 1 hour. Target-MBs with any bound DNA (round 1 aptamers) are magnetically collected. The DNA-target-MB complexes are washed three times in 400 .mu.l of sterile 1.times.BB. Following the third wash, the DNA-target-MB pellet (about 75 .mu.l) is used in a PCR reaction to amplify the bound DNA as follows. The MB pellet is split into 15 .mu.l aliquots and added to five pre-made PCR tubes which contain most of the nonperishable ingredients of a PCR reaction beneath a wax seal. A total of 3 .mu.l of 1:10 primer mix (10% forward primer plus 10% reverse primer) in nuclease-free deionized water or .about.20 nanomoles of each primer per ml plus 1 .mu.l (5 U) of Taq DNA polymerase and 5 .mu.l of 2 mM MgCl.sub.2 are added to each of the five tubes. PCR reactions are supplemented with 0.5 .mu.l of E. coli single-strand binding protein (SSBP, Stratagene Inc., La Jolla, Calif.) to inhibit high molecular weight concatamer (end to end aggregates of the DNA ligands) formation. PCR is carried out as follows: an initial 95.degree. C. phase for 5 minutes, followed by 20 cycles of 1 minute at 95.degree. C., 1 minute at 53.degree. C., and 1 minute at 72.degree. C. followed by a 72.degree. C. completion stage for 7 minute, and refrigeration at 4.degree. C. This constitutes the first of multiple rounds of MB-aptamer development. Iterations of the MB-aptamer development process are repeated until the desired affinity or assay sensitivity and specificity are achieved. Typically, 5-10 rounds of the MB-aptamer development process are required to achieve low ng/ml detection of target analytes. To begin the second round and all subsequent rounds, 4 complete tubes of the 5 original PCR tubes are heated to 95.degree. C. for 5 minutes to release bound DNA from the target-MBs. The fifth tube is always retained and refrigerated as a back-up for that round of the aptamer generation process. All available DNA (25 .mu.l per tube) is siphoned out of the hot tubes without removing the target-MBs before the tubes cool significantly and the DNA is pooled. The 100 .mu.l of hot DNA is added to 100 .mu.l of fresh target-MBs in 200 .mu.l of 2.times.BB and allowed to mix for 1 hr at RT. Thereafter, the selection and amplification process are repeated for 3-8 more rounds with checking for 72 bp aptamer PCR products by ethidium bromide-stained 2% agarose electrophoresis after each round. Following the last round of aptamer development, aptamers are cloned into chemically competent E. coli using a cloning kit from Lucigen Corp. (Middleton, Wis.) and clones are sent to Sequetech, Inc. (Mountain View, Calif.) for DNA sequencing.

Screening of Aptamers for Highest Affinity, Lowest Cross-Reactivity and to Determine Lower Limit of Detection by Target Titration in ELISA-Like Plate Assay ("ELASA")

[0050] To evaluate, screen, and rank aptamers based on affinity against clinically relevant targets, an enzyme-linked plate assay is conducted by first immobilizing 100 .mu.l of 1:10 diluted target (about 0.1 mg of total protein, peptide or small molecule) in 0.1M NaHCO.sub.3 (pH 8.5) overnight at 4.degree. C. in a covered polystyrene 96-well plate. The plate is decanted and washed three times in 250 .mu.l of 1.times.BB. Each of the different 5'-biotinylated aptamers raised against the target is dissolved in 1.times.BB at 1.00 nmoles to 4.50 nmoles per 100 microliters and applied to their corresponding plate wells for 1 hour at room temperature (RT; .about.25.degree. C.) with gentle mixing on an orbital shaker. The plate is decanted and washed three times in 250 .mu.l of 1.times.BB for at least 5 minutes per wash with gentle mixing. One hundred .mu.l of a 1:2,000 dilution of streptavidin-peroxidase from a 5 mg/ml stock solution in 1.times.BB is added per well for 30 minutes at RT with gentle mixing. The plate is decanted and washed three times with 250 .mu.l of 1.times.BB per well as before. One hundred .mu.l of ABTS (2,2'-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid) substrate with stabilized hydrogen peroxide (Kirkegaard Perry Laboratories, Inc., Gaithersburg, Md.) is added per well for 10 minute at RT. Finally absorbance is quantified using a microplate reader with 405 nm optical filter.

[0051] As Tables 1-8 illustrate for several cardiovascular biomarker targets (Brain Natriuretic Peptide; BNP, D-Dimer; DD, Creatine Kinase-MB types I and II; MBI and MB2, Interleukin-18; IL18, and Troponin-T; Tpn all at (1 .mu.g/ml) the initial ELASA screening is useful for ranking the relative affinity of aptamers for their respective targets by simple ranking of absorbance values at 405 nm from highest to lowest. Each of the Tables (1-8) illustrates general consistency between ELASA trials as well (i.e., the highest affinity aptamers consistently rank among the highest absorbance values between ELASA trials or plates 1-4 maximally).

TABLE-US-00001 TABLE 1 DNA Ligand ELASA Rankings for Brain Natriuretic Peptide (BNP) Well Aptamer A 405 nm Plate 1 A12 BNP - 6R 2.766 C1 BNP - 14bF 2.283 A3 BNP - 2F 2.276 B1 BNP - 7F 2.227 E3 BNP - 25cf 2.215 A1 BNP - 1F 2.184 B4 BNP - 8R 2.176 A8 BNP - 4/9R 2.163 C3 BNP - 15aF 2.162 D4 BNP - 21bR 2.149 Plate 2 A12 BNP - 6R 2.171 A3 BNP - 2F 2.110 C1 BNP - 14bF 2.089 A8 BNP - 4/9R 1.989 A1 BNP - 1F 1.987 B9 BNP - 13F 1.986 A9 BNP - 5/11/15b/19/25bF 1.977 C2 BNP - 14bR 1.971 D9 BNP - 23bF 1.961 B4 BNP - 8R 1.953 Plate 3 A12 BNP - 6R 2.285 D5 BNP - 22F 2.272 E3 BNP - 25cF 2.240 D4 BNP - 21bR 2.212 C1 BNP - 14bF 2.206 B4 BNP - 8R 2.197 A9 BNP - 5/11/15b/19/25bF 2.196 A3 BNP - 2F 2.176 C3 BNP - 15aF 2.165 B5 BNP - 10F (70) 2.157

TABLE-US-00002 TABLE 2 DNA Ligand ELASA Rankings for D-Dimer (DD) Well Aptamer A 405 nm Plate 1 A10 DD - 5R 1.888 B10 DD - 12R 1.427 C7 DD - 17F (71) 1.261 B8 DD - 11R (71) 1.122 B12 DD - 13R (71) 1.088 B1 DD - 7F (71) 1.027 B7 DD - 11F (71) 1.021 B2 DD - 7R (71) 1.017 A12 DD - 6R (71) 0.989 C12 DD - 20R (71) 0.952 Plate 2 A10 DD - 5R 1.809 A4 DD - 2R (71) 1.620 C7 DD - 17F (71) 1.237 B10 DD - 12R 1.213 A12 DD - 6R (71) 1.005 B7 DD - 11F (71) 1.003 B8 DD - 11R (71) 0.986 B1 DD - 7F (71) 0.964 C11 DD - 20F (71) 0.932 B6 DD - 10R (71) 0.930 Plate 3 B1 DD - 7F (71) 0.803 C1 DD - 14F (71) 0.652 A10 DD - 5R 0.576 B4 DD - 9R (71) 0.545 B2 DD - 7R (71) 0.510 C4 DD - 15R 0.508 B5 DD - 10F (71) 0.418 C12 DD - 20R (71) 0.404 B10 DD - 12R 0.386 A5 DD - 3F (71) 0.370 Plate 4 C1 DD - 14F (71) 0.816 B1 DD - 7F (71) 0.806 A10 DD - 5R 0.749 B10 DD - 12R 0.732 B4 DD - 9R (71) 0.645 C3 DD - 15F 0.635 B5 DD - 10F (71) 0.563 B2 DD - 7R (71) 0.535 A5 DD - 3F (71) 0.526 C4 DD - 15R 0.512

TABLE-US-00003 TABLE 3 DNA Ligand ELASA Rankings for Creatine Kinase-MB Type I (MBI) Well Aptamer A 405 nm Plate 1 F1 MBI - 20F 2.917 D2 MBI - 1/4/5/8/9/17R (71) 2.725 D6 MBI - 3R (70) 2.668 E10 MBI - 16R 2.665 E1 MBI - 11F 2.658 E2 MBI - 11R 2.651 E11 MBI - 19F (69) 2.589 E7 MBI - 15F 2.578 D1 MBI - 1/4/5/8/9/17F (71) 2.556 D4 MBI - 2R (71) 2.522 Plate 2 F1 MBI - 20F 2.692 D2 MBI - 1/4/5/8/9/17R (71) 2.680 D6 MBI - 3R (70) 2.647 E1 MBI - 11F 2.612 E10 MBI - 16R 2.612 D3 MBI - 2F (71) 2.511 E2 MBI - 11R 2.499 D1 MBI - 1/4/5/8/9/17F (71) 2.497 F2 MBI - 20R 2.424 D4 MBI - 2R (71) 2.419 Plate 3 F1 MBI - 20F 1.863 D2 MBI - 1/4/5/8/9/17R (71) 1.858 D3 MBI - 2F (71) 1.808 E3 MBI - 12F (70) 1.753 E2 MBI - 11R 1.716 E5 MBI - 14/18F 1.692 D4 MBI - 2R (71) 1.663 E4 MBI - 12R (70) 1.642 E1 MBI - 11F 1.640 F2 MBI - 20R 1.619 Plate 4 F1 MBI - 20F 1.948 D3 MBI - 2F (71) 1.823 D6 MBI - 3R (70) 1.746 D2 MBI - 1/4/5/8/9/17R (71) 1.744 F2 MBI - 20R 1.742 D1 MBI - 1/4/5/8/9/17F (71) 1.733 E2 MBI - 11R 1.659 E3 MBI - 12F (70) 1.647 D5 MBI - 3F (70) 1.629 D4 MBI - 2R (71) 1.607

TABLE-US-00004 TABLE 4 DNA Ligand ELASA Rankings for Creatine Kinase-MB Type II (MBII) Well Aptamer A 405 nm Plate 1 G1 MBII - 6/8F 2.206 G12 MBII - 12R (71) 2.191 F12 MBII - 5R 2.173 H6 MBII - 14R 1.989 G4 MBII - 7R 1.910 H7 MBII - 15F (71) 1.838 G11 MBII - 12F (71) 1.827 H5 MBII - 14F 1.794 F10 MBII - 4R (71) 1.751 G9 MBII - 11F 1.732 Plate 2 G1 MBII - 6/8F 2.120 G4 MBII - 7R 1.931 G12 MBII - 12R (71) 1.850 H5 MBII - 14F 1.688 F7 MBII - 3F (71) 1.682 G5 MBII - 9F 1.675 G11 MBII - 12F (71) 1.640 H7 MBII - 15F (71) 1.611 F12 MBII - 5R 1.588 F9 MBII - 4F (71) 1.586

TABLE-US-00005 TABLE 5 DNA Ligand ELASA Rankings for Interleukin-18 (IL18) Aptamer Well A 405 nm Plate 1 IL18 - 29F D1 1.433 IL18 - 10F B1 1.428 IL18 - 5F A7 1.393 IL18 - 22R C4 1.373 IL18 - 21R C2 1.367 IL18 - 21F C1 1.270 IL18 - 29R D2 1.219 IL18 - 3F A3 1.217 IL18 - 15R B6 1.209 IL18 - 22F C3 1.204 Plate 2 IL18 - 22R C4 1.738 IL18 - 21R C2 1.697 IL18 - 10F B1 1.673 IL18 - 29F D1 1.655 IL18 - 5F A7 1.596 IL18 - 22F C3 1.594 IL18 - 26F (71) C7 1.553 IL18 - 21F C1 1.534 IL18 - 29R D2 1.528 IL18 - 30F (71) D3 1.525 Plate 3 IL18 - 29F D1 1.288 IL18 - 21R C2 1.202 IL18 - 22R C4 0.993 IL18 - 10F B1 0.917 IL18 - 26F (71) C7 0.886 IL18 - 22F C3 0.855 IL18 - 2F A1 0.844 IL18 - 29R D2 0.795 IL18 - 5F A7 0.791 IL18 - 4R A6 0.785 Plate 4 IL18 - 21R C2 1.060 IL18 - 26F (71) C7 0.841 IL18 - 4R A6 0.835 IL18 - 22F C3 0.677 IL18 - 22R C4 0.662 IL18 - 27/31F (70) C9 0.613 IL18 - 33R D8 0.608 IL18 - 27/31R (70) C10 0.601 IL18 - 5F A7 0.589 IL18 - 29F D1 0.550

TABLE-US-00006 TABLE 6 DNA Ligand ELASA Rankings for Troponin-T (Tpn) Aptamer Well A 405 nm Plate 1 Tpn - 20F (71) H3 2.325 Tpn - 12R (71) G2 2.070 Tpn - 20R (71) H4 2.053 Tpn - 7F (71) F3 2.030 Tpn - 18F H1 1.986 Tpn - 18R H2 1.971 Tpn - 6R (71) F2 1.962 Tpn - 1R (71) E2 1.949 Tpn - 15F (71) G7 1.898 Tpn - 1F (71) E1 1.871 Plate 2 Tpn - 20F (71) H3 2.642 Tpn - 20R (71) H4 2.479 Tpn - 1F (71) E1 2.374 Tpn - 12R (71) G2 2.357 Tpn - 6R (71) F2 2.342 Tpn - 18R H2 2.304 Tpn - 7F (71) F3 2.298 Tpn - 12F (71) G1 2.252 Tpn - 1R (71) E2 2.249 Tpn - 6F (71) F1 2.195 Plate 3 Tpn - 2OF (71) H3 2.482 Tpn - 2OR (71) H4 2.249 Tpn - 16R (71) G10 1.854 Tpn - 16F (71) G9 1.811 Tpn - 6R (71) F2 1.656 Tpn - 7F (71) F3 1.599 Tpn - 15R (71) G8 1.535 Tpn - 9R F8 1.517 Tpn - 1F (71) E1 1.487 Tpn - 4bR (71) E10 1.477 Plate 4 Tpn - 20F (71) H3 2.507 Tpn - 20R (71) H4 2.259 Tpn - 16F (71) G9 1.525 Tpn - 6R (71) F2 1.514 Tpn - 16R (71) G10 1.507 Tpn - 18F H1 1.396 Tpn - 11F (71) F11 1.386 Tpn - 4bR (71) E10 1.350 Tpn - 1F (71) E1 1.318 Tpn - 7F (71) F3 1.264

TABLE-US-00007 TABLE 7 DNA Ligand ELASA Rankings for C-Reactive Protein (CRP) Rank Aptamer Abs 405 nm 1 CRP-5R 2.332 2 CRP-10R 2.27 3 CRP-2R 2.210 4 CRP-11R 2.173 5 CRP-17R 2.165 6 CRP-23F 2.139 7 CRP-10F 2.100 8 CRP-2F 2.072 9 CRP-9R 2.066 10 CRP-9F 2.055

TABLE-US-00008 TABLE 8 DNA Ligand ELASA Rankings for Myoglobin (Myo) Rank Aptamer Abs 405 nm 1 Myo-3R/4R 2.395 2 Myo-22F 2.367 3 Myo-15F 2.344 4 Myo-3F/6F 2.337 5 Myo-5R 2.327 6 Myo-24F 2.294 7 Myo- 2.272 18R/27F 8 Myo-15R 2.269 9 Myo-28F 2.264 10 Myo-8F 2.250

Aptamer Beacons and Competitive FRET-Aptamer Assays

[0052] Once key aptamers have been identified by the commonality of their sequences or their secondary stem-loop structures, the assay developer decides upon secondary structure loops (potential binding pockets) to label with a fluorophore (F) or quencher (Q) as illustrated by dotted lines that define the borders or limits of potential binding loops in FIGS. 2 and 8. Secondary stem-loop structures are easily generated by Gibbs free energy minimization with common software such as M-fold and Vienna RNA (using DNA parameters) that is freely available for public use. The researcher or inventor simply enters the DNA sequence and selects a temperature and secondary stem-loop structures like those shown in FIG. 2 are generated. At this point, one can empirically assess candidate aptamer "beacon" potential in FRET analyte titration experiments such as those shown in FIGS. 3A-3F. The suspected short aptamer beacon loop is re-synthesized independent of the original larger parent aptamer sequence with a fluorophore (F) such as TYE 665 attached to the 5' end and a matched quencher (Q) such as Iowa Black attached to the 3' end (or vice versa), purified by HPLC or other form of chromatography and assessed for fluorescence output or intensity as a function of different levels of the target analyte (e.g., FIGS. 3A-3F and FIGS. 9A-9D). The greatest separation of fluorescence peak values or spectral emissions (e.g., FIGS. 3A-3F and FIGS. 9A-9D) is used to define the optimal beacon since separation of fluorescence values as a function of analyte concentration is essentially the definition of a good quality fluorescence assay.

[0053] Alternatively, one may label the suspected binding loops internally and place an F or a Q somewhere in the mid-section of the suspected loop other than the 3' or 5' end (i.e., intrachain FRET). Attachment of F or Q is usually accomplished via succinimide linkage of F- or Q-succinimides added to amino-modified aptamers at specifically chosen locations in the binding pockets. Primary amine linker moieties such as the "UniLink.TM." can be added internally at the time of chemical synthesis of aptamers. Typically 1 mg or more of an aptamer sequence is synthesized with a primary amine linker moiety (UniLink.TM.) located at the approximate center of each loop structure (suspected binding pockets). Each of these internally amine-labeled aptamers is then labeled with 100 .mu.l (0.1 mg) of F-succinimide (or alternatively Q-succinimide) for 2 hours in a 37.degree. C. incubator, followed by purification through a 1.times.BB-equilibrated PD-10 (Sephadex G-25; GE Healthcare) column. In the meantime, an equal molar amount of primary amine-modified target molecule is labeled with 0.1 mg of spectrally matched Q-succinimide (to accept photons from F) at 37.degree. C. for 2 hours and then washed three times by centrifugation at 14,000 rpm for 10 minutes per wash and resuspension in 1 ml of 1.times.BB. "Spectrally matched" means that most of the wavelengths of light emitted by F can be effectively absorbed by Q because its absorbance spectrum largely overlaps the emission spectrum of F. Naturally, if the aptamer is labeled with a Q-succinimide in the alternate form of the assay, the amine-modified target must be labeled with an appropriately matched F-succinimide to be quenched when bound to the Q-labeled aptamer. Pooled one ml fractions of purified F-labeled DNA aptamers are mixed with an equimolar amount of Q-labeled-amino-target analyte (or vice versa in the alternate embodiment) for 30 minutes at RT with mixing in 1.times.BB or phosphate buffered saline (PBS, 0.1M phosphates in 8.5 g/L sodium chloride at pH 7.2 to 7.4) and then purified through an appropriate size-exclusion chromatography column (according to molecular weight of the combined F-aptamer plus Q-target complex) to produce a purified "competitive FRET complex" consisting of F-aptamer conjugate bound to Q-labeled target. This competitive FRET complex can later be competed against unlabeled cognate analyte concentrations to increase the fluorescent light output of the liquid assay system and quantify the unlabeled analyte concentration.

[0054] Generally, the aptamer beacons or competitive FRET-aptamer complexes are then diluted to a final concentration of 1-5 .mu.g/ml in 1.times.BB and equally dispensed to polystyrene or methacrylate cuvettes in which 1 ml of unlabeled target at various concentrations in 1.times.BB, PBS or diluted blood, plasma, serum, saliva, aspirate or urine has been added already. Cuvettes are gently mixed for 15 to 20 minutes at RT prior to reading their fluorescence in the homogeneous beacon or competitive-displacement FRET assay formats using a spectrofluorometer having gratings to vary the excitation wavelength and emission scanning ability or a stationary, handheld or otherwise portable fluorometer having a more restricted or fixed excitation and emission optical filter set with a range of wavelengths for excitation and emission.

Aptamer or Aptamer Binding Site Linkage in One or More Dimensions

[0055] The linkage of binding sites is beneficial in terms of enhancing receptor affinity, avidity (tensile binding strength), and selectivity versus complex targets with two or more distinct epitopes. This linkage can be sequential and linear (one-dimensional as in antibody heavy and light chain linkage of HV regions, FIG. 1A) or could be expanded into two or three dimensions much like DNA dendrimers or other more complex structures known to those skilled in the art. Linear linkage by chemical synthesis is quite facile, if one knows that aptamer DNA sequences or shorter (approximately 5-10 base) binding site sequences to be linked. One can simply design one long sequence to incorporate the desired aptamers or binding sites with repetitive poly-adenine (A), poly-cytosine (C), poly-guanine (G), poly-thymine (T), poly-uridine (U), or other intervening sequences that are unlikely to bind the target epitopes. The length of the composite aptamer construct will be limited by current chemical synthesis technology to about 200 bases. However, cellular biosynthesis or enzymatic synthesis by polymerase chain reaction (PCR) or asymmetric PCR (producing predominately single-stranded ss-DNA from a template) would not be so limited and should produce aptamer constructs up to 2,000 bases before the Taq polymerase falls off the template. The 2 kilobase Taq polymerase limit is the basis for the well-known RAPD (Random Amplification of Polymorphic DNA) method of DNA or genetic "fingerprint" analyses in which primers greater than 2 kilobases apart fail to produce a PCR product or amplicon, because Taq becomes disengaged from the template DNA before traveling 2,000 bases. In this way, lengthy aptamer constructs of less than 2 kilobases could be made from complementary DNA templates that would enable binding of different epitopes that are distal on the surface of relatively large objects such as viruses and whole bacterial or eukaryotic cells. Again, poly-A, C, G, T, or U or other linker nucleotide segments could be designed into the cDNA template to produce the resultant nascent strand to ligate aptamers or aptamer binding sites together into one contiguous linear chain with intervening linkers.

[0056] For 2-D or 3-D linked aptamer structures a variety of linker chemistries are available, but the preferred embodiment is probably addition of a UniLink.TM. primary amine group somewhere in the mid-section of a larger multi-aptamer construct followed by covalent linkage of two or more such multi-aptamer constructs by means of bifunctional linkers such as low levels (.ltoreq.1%) of glutaraldehyde, carbodiimides, sulfo-EGS, sulfo-SMCC or other such bifunctional linkers familiar to those skilled in conjugate chemistry. This strategy would result in a larger flower-like 2-D or 3-D structure consisting of two or more-lengthy multi-aptamer structures.

[0057] Referring to the figures, FIG. 1A illustrates the general structure of an IgG antibody showing the linkage of hypervariable (HV) amino acid regions used for actual binding to target epitopes on complex antigens. Linear linkage of HV binding sites adds affinity, avidity and specificity the antibody binding to complex targets. Likewise in FIG. 1B, aptamers or their shorter (5-10 base) binding sites can be linked during chemical or biochemical (enzymatic) synthesis to enhance aptamer binding affinity, avidity or specificity for improved assay sensitivity and selectivity.

[0058] FIG. 2 is a diagram of secondary structures for two "finalists" (SEQ ID NOs 3 and 4) from the pool of 24 unique candidate aptamers (SEQ ID NOs. 1-24) that bind human Type I bone collagen C-telopeptide (CTx) indicative of bone loss when found in the urine. These 2 aptamer sequences (forward and reverse or F and R-primed) dominated the aptamer pool (12 of 38 total clones=31.6%) and were therefore considered prime candidates to investigate for possible binding pockets (secondary loop structures). These potential binding pockets are shown as loops cut off from the rest of the aptamer by dotted lines and designated according to the 12 hour clock as 2 O'clock (or second hour or 2 h), 6 O'clock (6 h) and 10 O'clock (10 h). The overall 5' and 3' ends as well as a numbering system from bases 1 (at the 5' end) to base 72 (at the 3' end) are also indicated. A variation on the CTx 2R-2 h loop or beacon consisting of 13 and 15 bases (13b or 15b) is also indicated. The 2 O'clock or second hour (2 h) aptamer was subsequently synthesized to produce an aptamer beacon (3' end labeled with a quencher molecule and the 5' end labeled with a fluorophore) as demarcated by the dotted lines which is capable of detecting CTx peptide to low nanogram per ml levels.

[0059] FIGS. 3A-3F show how each of the aptamer beacons derived and defined from FIG. 2 behaved as a function of decreasing CTx peptide concentration (serial two-fold dilutions beginning with 100 micrograms per ml and ending with zero CTx peptide) in 1.times. binding buffer (1.times.BB; 0.5 M NaCl, 10 mM Tris-HCl, pH 7.5-7.6, 1 mM MgCl.sub.2). In the figures "h" means hour or O'clock so that 2 h refers to the 2 O'clock loop from FIG. 2, while F means forward-primed and R means reverse-primed by reference to FIG. 2 as well. FIGS. 3A-3F demonstrate that there is in fact a significant difference in the ability of each candidate loop or candidate beacon from FIG. 2 to bind and detect a 26-amino acid (AA; full-length) CTx peptide in 1.times.BB. The figures show that the 15-base CTx 2R-2h loop (5'-GGTGGTGTTGGCTCC-3') acts as a superior aptamer beacon for detection of CTx peptide, because it gives the greatest fluorescence spread as a function of CTx peptide concentration. The CTx 2R-2h loop was optimal for FRET-based detection because it gives the greatest spread or separation for various two-fold serial dilutions of the 26-AA CTx peptide beginning at 100 .mu.g/ml. The CTx 2F-10 h loop was also noteworthy, but could not discriminate many of the different CTx concentrations. The candidate loops or beacons from this experiment were 5' labeled with TYE665 fluorophore and 3' labeled with Iowa Black RQ quencher and HPLC-purified prior to use at Integrated DNA Technologies, Inc. (Coralville, Iowa). Excitation on a spectrofluorometer was at 645 nm with 5 nm slits and a PMT (photomultiplier tube) setting of 900V. A slightly shorter 13-base version of the CTx-2R-2h beacon ((5'-GTGGTGTTGGCTC-3') has also been shown to work almost as well as the 15-base version, but has slightly higher background fluorescence. Excitation in all cases was at 645.+-.5 nm to maximally excite TYE 665 dye (fluorophore) on the 5' end of each potential aptamer beacon with a photomultiplier tube (PMT) detector setting of 1,000 Volts.

[0060] FIGS. 4A and B demonstrate relative specificity of the CTx 2R-2h aptamer beacon. FIG. 4A illustrates specificity or preference of the beacon for binding to the full-length 26-AA version of the CTx peptide based on its more intense fluorescence with the full-length CTx peptide, but not with a shorter 8-amino acid segment of the same peptide using a spectrofluorometer. Since the 8-AA version of the CTx peptide (one letter amino acid sequence: EKAHDGGR) represents a subset of the larger 26-AA peptide (amino acid sequence: SAGFDFSFLPQPPQEKAHDGGRYYRA), this observation indicates where the aptamer does not bind on the larger CTx peptide and narrows down the possible binding sites to SAGFDFSFLPQPPQ or YYRA). The aptamer beacon does unexpectedly cross-react with and bind an epitope on bovine serum albumin (BSA) and since the 607 amino acid BSA protein shares its longest region of commonality with the CTx peptide at the amino acid sequence SFL or serine-phenylalanine-leucine, this may be the actual binding site of the CTx 2R-2h aptamer beacon to CTx bone peptide, although other sites cannot be ruled out completely. Again, intact bovine proteins and epitopes are not expected in human clinical samples, making the CTx 2R-2h aptamer beacon specific for its target bone peptide.

[0061] FIG. 4B shows the same samples FIG. 4A evaluated by a handheld fluorometer that only reports fluorescence peak height, but confirms the level of specificity seen in the spectra above. The beacon was again 5' labeled with TYE665 fluorophore and 3' labeled with Iowa Black quencher and HPLC-purified prior to use in assays. Excitation on the spectrofluorometer was at 645 nm with 5 nm slits and a PMT (photomultiplier tube) setting of 900V. Handheld fluorometer values were obtained with an optically modified (red light emitting diode with peak excitation at 650 nm with a 660-720 nm emission filter) Quantifluor.TM. device from Promega Corp. Other abbreviations used in FIGS. 3A-3F are: NTx; N-terminal telopeptide of human Type I bone collagen, HP; helical peptide of human bone, BSA; bovine serum albumin, DPD; deoxypyridinoline, and Pyd; pyridinoline.

[0062] FIG. 5 compares the 15-base CTx 2R-2h aptamer beacon assay's titration versus different levels of the full-length CTx peptide (26 amino acids) in 1.times. binding buffer for 30 minutes at room temperature as assessed by the handheld Quantifluor.TM. from 0 to 32 ng/ml of CTx peptide with a limit of detection (LOD) of 1 ng/ml with a photodiode standard value setting of 999.0. It shows the relative linearity and sensitivity of the 15-base CTx 2R-2h aptamer beacon assay.

[0063] FIGS. 6A and 6B illustrate the linear normalization response of three different aptamer beacons raised against creatinine from the SEQ ID NOs 239-294 family to the denaturing effects of creatinine across the physiologic range found in human urine. The non-specific linear response of aptamer beacons in general to the denaturing (linearizing) effects of creatinine and urea across the physiologic range of these substances found in human urine suggest that addition of almost any aptamer beacon to urine could be used to estimate creatinine and urea levels in urine and normalize the values for other analytes in urine. It is a common practice in clinical diagnostics in which the creatinine or urea level of urine is used as a divisor for the amount of other analytes detected in urine to normalize readings between different patients. In essence, the creatinine or urea levels indicate how concentrated the urine is and that information can be used to adjust or normalize (divide by) the creatinine level to place the levels of other analytes in proper perspective (i.e., high analyte levels in a dehydrated individual may be misleading). Quantitative estimation of creatinine and urea levels in urine or serum using the aptamer beacon denaturation approach is simple (one step bind and detect), rapid (within 10-15 minutes) and facile as compared to the more complicated multi-component alkaline picrate colorimetric and time-consuming Jaffe method (i.e., results obtained greater than 35 minutes after reagent and sample preparation).

[0064] FIGS. 7A and 7B illustrate that the 2,942 dalton (26 amino acid) CTx peptide can be extracted from urine to avoid the denaturing effects of creatinine and urea on the CTx 2R-2h aptamer beacon assay (demonstrated in FIG. 5) by use of a desalting size-exclusion polyacrylamide column. FIG. 7A shows fractions collected from a desalting column (with a 1,800 dalton molecular weight cut off) and run in an 8% polyacrylamide-sodium dodecyl sulfate (SDS) electrophoresis gel which was run against molecular weight protein standards (last lane) and Coomassie blue stained to reveal the location of the 2.9 kilodalton CTx peptide which emerged in the void volume fractions 4 and 5 (boxed). The far right lane of this gel shows molecular weight protein standards beginning at 5 kD. FIG. 7B shows that CTx peptide extracted from human urine by means of a desalting column can still be sensitively detected to a level of at least 122 ng/ml by the CTx 2R-2h aptamer beacon.

[0065] FIG. 8 illustrates the secondary stem-loop structures of several candidate aptamers (SEQ ID NOs 433 and 434) which dominated the sequenced pool of vitamin D3 aptamers (abbreviated VD3 and from the SEQ ID NOs 429-526). Again, the lines and capital letters demarcate the loops which were considered further as binding pockets or for aptamer beacons to detect vitamin D and its isoforms or congeners.

[0066] FIGS. 9A-9D illustrate the FRET responses of loops A, B, and C for the VD3 aptamers shown in FIG. 8 as well as handheld (Quantifluor.TM.-P) fluorometer peak fluorescence values as a function of 25-hydroxy-vitamin D3 (calcidiol) level in 1.times.BB. Loop C (5'-ACTATGGT-3') proved to be the optimal aptamer beacon based on its maximal spread or separation of fluorescence spectra as a function of vitamin D concentration as shown in the upper right quadrant after Loop C was separately synthesized with 5'-TYE 665 dye and 3'-Iowa Black quencher to convert it into a beacon for the titration experiment. The spectra were obtained by serial two-fold dilutions of calcidiol beginning at 100 .mu.g/ml in 1.times.BB. The candidate VD3 loop beacons were 5' labeled with TYE665 fluorophore and 3' labeled with Iowa Black quencher and HPLC-purified prior to use in assays. Excitation on a spectrofluorometer was at 645 nm with 5 nm slits and a PMT setting of 900 V. Handheld fluorometer values (lower right quadrant) were obtained with an optically modified (red light emitting diode with peak excitation at 650 nm with a 660-720 nm emission filter) Quantifluor.TM.-P device from Promega Corp. and show a lower limit of detection of about 195 ng/ml in 1.times.BB.

[0067] FIGS. 10A-10C show that the VD3 Loop C beacon appears to react equally well with 1-hydroxy vitamin D2, 1-hydroxy-vitamin D3 and 25-hydroxy-vitamin D3 as assessed by spectrofluorometry in 1.times.BB (binding buffer). Hence the Loop C beacon is only specific for the vitamin D family and cannot discriminate individual congeners. Cross-reactivity is not problematic since a number of immunoassays for vitamin D detect the total of the major forms of vitamin D2 and D3 together. Hence, the inability of the Loop C VD3 aptamer to discriminate the minor variants of vitamin D is not viewed as a limiting factor. The figures again show serial two-fold dilutions for each of the types of vitamin D beginning at 100 .mu.g/ml in 1.times.BB with 1-hydroxy-vitamin D2 spectra in the top panel, 1-hydroxy-vitamin D3 spectra in the middle panel, and 25-hydroxy-vitamin D3 spectra in the bottom panel.

[0068] FIG. 11 shows a graphical assessment of the VD3 Loop C beacons by the handheld fluorometer (Quantifluor.TM.-P) in 1.times.BB across a range of various vitamin D concentrations and for various forms of vitamin D. The handheld reader was modified with a red-emitting (650 nm) LED light source and 660-720 nm emission filter to better work in serum where the red region optics (>600 nm) can avoid much of the blue-green (<600 nm) autofluorescence background of blood, serum or urine. The range shown on the x-axis spans much higher levels than previously shown. Some of the higher levels are not physiological, but might be relevant to detection of vitamin D is some vitamin-rich foods or dairy products. Lines of best fit, whether linear or exponential, are shown for the three different types of vitamin D congeners as well. The highest standard value photodetector setting of 999.0 was used in all cases.

[0069] FIGS. 12A and 12B further assess the specificity or cross-reactivity of the VD3 Loop C aptamer beacon versus a variety of potential analytes or interfering species commonly found in blood and urine by the customized handheld fluorometer (FIG. 12A) and by spectrofluorometry (FIG. 12B) H-DPD; hydroxy-deoxypyridinoline and H-Pyd; hydroxyl-pyridinoline cross linkers from bone.

[0070] FIGS. 13A and 13B show fluorometric spectra from two separate trials of a competitive displacement FRET assay using the VD3 Loop C beacon versus various levels of 25-hydroxy-vitamin D3 (two-fold serial dilutions starting at 100 .mu.g/ml) in 1.times.BB. In this case, 25-hydroxy-vitamin D3 was labeled with carboxyfluorescein by Fisher esterification (reaction of a hydroxyl group on the vitamin with a carboxyl group on the fluorescein to form a covalent ester bond at acidic pH of approximately 5) followed by binding to appropriately quencher-labeled VD3 aptamer Loop C and competition against levels of calcidiol.ltoreq.100 micrograms per ml).

[0071] FIG. 14 shows the same samples from FIGS. 13A and 13B assessed for fluorescence peak height by the customized red-emitting handheld fluorometer assessed with the highest standard value photodetector setting of 999.0. The competitive FRET-aptamer assay appears to have a detection limit between 156 to 312 ng/ml in these experiments.

[0072] FIGS. 15A-15D show four examples of aptamers from the SEQ ID NOs 325-526 that bind recombinant human growth hormone (r-hGH; >95% pure research grade) better than the natural form of hGH or somatotropin in ELISA-like assays to help discriminate the artificial form of hGH in potential drug or doping tests for athletes, or to monitor serum levels of exogendus doses of r-hGH administered to children with growth deficits. The ELISA-like assays were conducted with the named aptamers (SEQ ID NOs 336, 338, 343 and 345) instead of antibodies in each case and absorbances were red at 405 nm with an automated microplate reader after a 15 minute development time in the presence of ABTS substrate as is standard in the diagnostics industry.

[0073] FIGS. 16A-16D show four more examples of aptamers (from the SEQ ID NOs 325-526) that bind recombinant human growth hormone ("r-hGH") better than the natural form of hGH or somatotropin to help discriminate the artificial form in potential drug or doping tests for atheletes and growth-challenged children. The ELISA-like assays were conducted with the named aptamers (SEQ ID NOs 348, 377, 379 and 388) instead of antibodies in each case and absorbances were red at 405 nm with an automated microplate reader after a 15 minute development time in the presence of ABTS substrate as is standard in the diagnostics industry.

[0074] FIG. 17A shows an experimental matrix screening scheme for capture aptamer-conjugated magnetic microbeads to be mixed with ruthenium trisbipyridine (Ru(bpy).sub.3.sup.2+)-labeled reporter aptamers in a sandwich assay scheme to determine which of the 7.times.7 top hGH and r-hGH aptamer combinations (numbered 1-49 in the scheme table) gave the strongest electrochemiluminescence ("ECL") signal versus 10 pg/ml of r-hGH using an IGEN International Origen.RTM. ECL analyzer in phosphate buffered saline containing 0.2 M tripropylamine ("TPA"). ECL was induced by ramping the electrode voltage to 1.25 V.

[0075] FIG. 17B shows the results of this ECL matrix screening process. Mean bar heights of three separate measurements are plotted with standard deviation error bars and the best (most intense ECL) combinations are marked with asterisks.

[0076] FIGS. 18A and 18B give ECL line plots for assay combinations 18 and 40 from the matrix in FIG. 17A as a function of natural hGH concentrations showing sub-picogram and sub-nanogram per ml detection limits and relative linearity over the hGH ranges indicated in 50% human serum (serum diluted 1:1 in 1.times.BB buffer). The difference in assay regression line slope is due to doubling of the amount of aptamer-coated magnetic beads and reporter aptamer per tube in two different assay trials.

[0077] FIG. 19A shows an experimental matrix screening scheme for capture aptamer-conjugated magnetic microbeads to be mixed with ruthenium trisbipyridine (Ru(bpy).sub.3.sup.2+)-labeled reporter aptamers in a sandwich assay scheme to determine which of the 4.times.4 top Brain or B-type Natriuretic Peptide ("BNP") aptamer combinations numbered 1-16 (and selected from the SEQ ID Nos. 527-562) gave the strongest ECL signal versus 100 ng of BNP using an IGEN International Origen.RTM. ECL analyzer in phosphate buffered saline containing 0.2 M TPA.

[0078] FIG. 19B shows the results of this ECL matrix screening process. Bar heights represent the means of three separate measurements plotted with standard deviation error bars and the best (most intense ECL) combinations are marked with asterisks.

[0079] FIG. 20A shows the linear ECL response for combination 4 (see FIG. 19A) sandwich assay versus picogram per ml levels of BNP in a 50% human serum and 1.times.BB diluent environment.

[0080] FIG. 20B shows cross-reactivity of the combination number 4 BNP assay versus other peptide or protein analytes that might be found at the 100 ng/ml level in human blood.

[0081] Although the invention and DNA ligand (aptamer) sequences have been described with reference to specific embodiments, these descriptions are not meant to be construed in a limited sense. Various modifications of the disclosed embodiments, as well as alternative embodiments of the inventions will become apparent to persons skilled in the art upon reference to the description of the invention. It is, therefore, contemplated that the appended claims will cover such modifications that fall within the scope of the invention.

Sequence CWU 1

1

906159DNAArtificial Sequencechemically synthesized 1atacgggagc caacaccact aacttgttgc tgatcttatc cagagcaggt gtgacggat 59259DNAArtificial Sequencechemically synthesized 2atccgtcaca cctgctctgg ataagatcag caacaagtta gtggtgttgg ctcccgtat 59372DNAArtificial Sequencechemically synthesized 3atacgggagc caacaccacc cgtttttgat ctaatgagga tacaatattc gtctagagca 60ggtgtgacgg at 72472DNAArtificial Sequencechemically synthesized 4atccgtcaca cctgctctag acgaatattg tatcctcatt agatcaaaaa cgggtggtgt 60tggctcccgt at 72572DNAArtificial Sequencechemically synthesized 5atacgggagc caacaccaat cgatggttag actattacac tagatggaat tcatagagca 60ggtgtgacgg at 72672DNAArtificial Sequencechemically synthesized 6atccgtcaca cctgctctat gaattccatc tagtgtaata gtctaaccat cgattggtgt 60tggctcccgt at 72772DNAArtificial Sequencechemically synthesized 7atacgggagc caacaccaat ctgccgacta ggccaagtaa ttatattcag ctggagagca 60ggtgtgacgg at 72872DNAArtificial Sequencechemically synthesized 8atccgtcaca cctgctctcc agctgaatat aattacttgg cctagtcggc agattggtgt 60tggctcccgt at 72959DNAArtificial Sequencechemically synthesized 9atacgggagc caacaccaca gctgatattg gatggtccgg cagagcaggt gtgacggat 591059DNAArtificial Sequencechemically synthesized 10atccgtcaca cctgctctgc cggaccatcc aatatcagct gtggtgttgg ctcccgtat 591172DNAArtificial Sequencechemically synthesized 11atacgggagc caacaccaca ttacaataga tgtattgaca tatccggaca gtcgagagca 60ggtgtgacgg at 721272DNAArtificial Sequencechemically synthesized 12atccgtcaca cctgctctcg actgtccgga tatgtcaata catctattgt aatgtggtgt 60tggctcccgt at 721372DNAArtificial Sequencechemically synthesized 13atacgggagc caacaccact cgtgtagtgc tgtctttgtg gaatccttgc atcgagagca 60ggtgtgacgg at 721472DNAArtificial Sequencechemically synthesized 14atccgtcaca cctgctctcg atgcaaggat tccacaaaga cagcactaca cgagtggtgt 60tggctcccgt at 721572DNAArtificial Sequencechemically synthesized 15atacgggagc caacaccacc acgtgaccca tacgatacaa caaataattg ctcaagagca 60ggtgtgacgg at 721672DNAArtificial Sequencechemically synthesized 16atccgtcaca cctgctcttg agcaattatt tgttgtatcg tatgggtcac gtggtggtgt 60tggctcccgt at 721772DNAArtificial Sequencechemically synthesized 17atacgggagc caacaccatc catagctcat ctataccctc ttccgagtcc caccagagca 60ggtgtgacgg at 721872DNAArtificial Sequencechemically synthesized 18atccgtcaca cctgctctgg tgggactcgg aagagggtat agatgagcta tggatggtgt 60tggctcccgt at 721972DNAArtificial Sequencechemically synthesized 19atacgggagc caacaccaga cgcggaacga ctcatcgcaa aatgtcgtga tgcaagagca 60ggtgtgacgg at 722072DNAArtificial Sequencechemically synthesized 20atccgtcaca cctgctcttg catcacgaca ttttgcgatg agtcgttccg cgtctggtgt 60tggctcccgt at 722172DNAArtificial Sequencechemically synthesized 21atacgggagc caacaccatg gttaggctgc tccatatatt cccgccccgc acgtagagca 60ggtgtgacgg at 722272DNAArtificial Sequencechemically synthesized 22atccgtcaca cctgctctac gtgcggggcg ggaatatatg gagcagccta accatggtgt 60tggctcccgt at 722369DNAArtificial Sequencechemically synthesized 23atacgggagc caacaccata gtgttgggcc aatacggtaa cgtgtccttg gagagcaggt 60gtgacggat 692469DNAArtificial Sequencechemically synthesized 24atccgtcaca cctgctctcc aaggacacgt taccgtattg gcccaacact atggtgttgg 60ctcccgtat 692572DNAArtificial Sequencechemically synthesized 25atacgggagc caacaccatg ctgaactaac agatacaaga tacagatccg agttagagca 60ggtgtgacgg at 722675DNAArtificial Sequencechemically synthesized 26atccgtcaca cctgctctaa ctcggatctg tatcttgtat ctgttagttc agcatggtgt 60tggctcccgt atata 752772DNAArtificial Sequencechemically synthesized 27atacgggagc caacaccatg tcgctggtca catccctagt taacaaactt ggatagagca 60ggtgtgacgg at 722872DNAArtificial Sequencechemically synthesized 28atccgtcaca cctgctctat ccaagtttgt taactaggga tgtgaccagc gacatggtgt 60tggctcccgt at 722972DNAArtificial Sequencechemically synthesized 29atacgggagc caacaccatt ggcgttacta gaggattact gaaagccata aactagagca 60ggtgtgacgg at 723072DNAArtificial Sequencechemically synthesized 30atccgtcaca cctgctctag tttatggctt tcagtaatcc tctagtaacg ccaatggtgt 60tggctcccgt at 723172DNAArtificial Sequencechemically synthesized 31atacgggagc caacaccatc actataattc cttcgaacct tacttgtgtt agctagagca 60ggtgtgacgg at 723272DNAArtificial Sequencechemically synthesized 32atccgtcaca cctgctctag ctaacacaag taaggttcga aggaattata gtgatggtgt 60tggctcccgt at 723372DNAArtificial Sequencechemically synthesized 33atacgggagc caacaccact atcgactttt acattcgtgt acgattcccg cttcagagca 60ggtgtgacgg at 723472DNAArtificial Sequencechemically synthesized 34atccgtcaca cctgctctga agcgggaatc gtacacgaat gtaaaagtcg atagtggtgt 60tggctcccgt at 723572DNAArtificial Sequencechemically synthesized 35atacgggagc caacaccatc ccctcgggcg agctatacta aaccagatcc taagagagca 60ggtgtgacgg at 723672DNAArtificial Sequencechemically synthesized 36atccgtcaca cctgctctct taggatctgg tttagtatag ctcgcccgag gggatggtgt 60tggctcccgt at 723772DNAArtificial Sequencechemically synthesized 37atacgggagc caacaccaag ctacacaacg aggcgtataa tcagcatgtt ggatagagca 60ggtgtgacgg at 723872DNAArtificial Sequencechemically synthesized 38atccgtcaca cctgctctat ccaacatgct gattatacgc ctcgttgtgt agcttggtgt 60tggctcccgt at 723972DNAArtificial Sequencechemically synthesized 39atacgggagc caacaccagg aaactactaa acgaacatga gctgtatcaa aaacagagca 60ggtgtgacgg at 724072DNAArtificial Sequencechemically synthesized 40atccgtcaca cctgctctgt ttttgataca gctcatgttc gtttagtagt ttcctggtgt 60tggctcccgt at 724172DNAArtificial Sequencechemically synthesized 41atacgggagc caacaccatc cagagtaaac gataaggggg aatctcaatg aaccagagca 60ggtgtgacgg at 724272DNAArtificial Sequencechemically synthesized 42atccgtcaca cctgctctgg ttcattgaga ttccccctta tcgtttactc tggatggtgt 60tggctcccgt at 724372DNAArtificial Sequencechemically synthesized 43atacgggagc caacaccaat actctcaaaa cctaacaaga caacccgagg gcccagagca 60ggtgtgacgg at 724472DNAArtificial Sequencechemically synthesized 44atccgtcaca cctgctctgg gccctcgggt tgtcttgtta ggttttgaga gtattggtgt 60tggctcccgt at 724572DNAArtificial Sequencechemically synthesized 45atacgggagc caacaccatg agactgggtc gatccaggac atacatttgt actaagagca 60ggtgtgacgg at 724672DNAArtificial Sequencechemically synthesized 46atccgtcaca cctgctctta gtacaaatgt atgtcctgga tcgacccagt ctcatggtgt 60tggctcccgt at 724772DNAArtificial Sequencechemically synthesized 47atacgggagc caacaccaga gccagaataa tggccccctt tacgagacga ctgtagagca 60ggtgtgacgg at 724872DNAArtificial Sequencechemically synthesized 48atccgtcaca cctgctctac agtcgtctcg taaagggggc cattattctg gctctggtgt 60tggctcccgt at 724972DNAArtificial Sequencechemically synthesized 49atacgggagc caacaccatc aggccgaaat gtatacgaag gtaagcgata aagtagagca 60ggtgtgacgg at 725072DNAArtificial Sequencechemically synthesized 50atccgtcaca cctgctctac tttatcgctt accttcgtat acatttcggc ctgatggtgt 60tggctcccgt at 725172DNAArtificial Sequencechemically synthesized 51atacgggagc caacaccagt cgtacgacac ccatccaaga ctttattccg cctaagagca 60ggtgtgacgg at 725272DNAArtificial Sequencechemically synthesized 52atccgtcaca cctgctctta ggcggaataa agtcttggat gggtgtcgta cgactggtgt 60tggctcccgt at 725372DNAArtificial Sequencechemically synthesized 53atacgggagc caacaccacg gtacaaactc tcaacaagct accactttag tccaagagca 60ggtgtgacgg at 725472DNAArtificial Sequencechemically synthesized 54atccgtcaca cctgctcttg gactaaagtg gtagcttgtt gagagtttgt accgtggtgt 60tggctcccgt at 725572DNAArtificial Sequencechemically synthesized 55atacgggagc caacaccact cgtttggccc acgagtcaat catatatcag ctaaagagca 60ggtgtgacgg at 725672DNAArtificial Sequencechemically synthesized 56atccgtcaca cctgctcttt agctgatata tgattgactc gtgggccaaa cgagtggtgt 60tggctcccgt at 725772DNAArtificial Sequencechemically synthesized 57atacgggagc caacaccatt attatcaaga cgctatctac agagattcac ggacagagca 60ggtgtgacgg at 725872DNAArtificial Sequencechemically synthesized 58atccgtcaca cctgctctgt ccgtgaatct ctgtagatag cgtcttgata ataatggtgt 60tggctcccgt at 725972DNAArtificial Sequencechemically synthesized 59atacgggagc caacaccagt gcgtgcgtgg cgacggtact actgactatg tcgtagagca 60ggtgtgacgg at 726072DNAArtificial Sequencechemically synthesized 60atccgtcaca cctgctctac gacatagtca gtagtaccgt cgccacgcac gcactggtgt 60tggctcccgt at 726172DNAArtificial Sequencechemically synthesized 61atacgggagc caacaccatg ccattcctgt gttagtctgt ccgttcgaca aggcagagca 60ggtgtgacgg at 726272DNAArtificial Sequencechemically synthesized 62atccgtcaca cctgctctgc cttgtcgaac ggacagacta acacaggaat ggcatggtgt 60tggctcccgt at 726372DNAArtificial Sequencechemically synthesized 63atacgggagc caacaccaga gtgttggcga taaacacaat gacccacagc cggaagagca 60ggtgtgacgg at 726472DNAArtificial Sequencechemically synthesized 64atccgtcaca cctgctcttc cggctgtggg tcattgtgtt tatcgccaac actctggtgt 60tggctcccgt at 726572DNAArtificial Sequencechemically synthesized 65atacgggagc caacaccatt ctggtgcgcg tgcaatgaga gaaatggctc gtacagagca 60ggtgtgacgg at 726672DNAArtificial Sequencechemically synthesized 66atccgtcaca cctgctctgt acgagccatt tctctcattg cacgcgcacc agaatggtgt 60tggctcccgt at 726772DNAArtificial Sequencechemically synthesized 67atacgggagc caacaccacc gcgttaaaga ggcgtacgat gtctcagtct cgccagagca 60ggtgtgacgg at 726872DNAArtificial Sequencechemically synthesized 68atccgtcaca cctgctctgg cgagactgag acatcgtacg cctctttaac gcggtggtgt 60tggctcccgt at 726972DNAArtificial Sequencechemically synthesized 69atacgggagc caacaccatt ctggtgcgcg tgcaatgaga gaaatggctc gtacagagca 60ggtgtgacgg at 727072DNAArtificial Sequencechemically synthesized 70atccgtcaca cctgctctgt acgagccatt tctctcattg cacgcgcacc agaatggtgt 60tggctcccgt at 727172DNAArtificial Sequencechemically synthesized 71atacgggagc caacaccacc gcgttaaaga ggcgtacgat gtctcagtct cgccagagca 60ggtgtgacgg at 727272DNAArtificial Sequencechemically synthesized 72atccgtcaca cctgctctgg cgagactgag acatcgtacg cctctttaac gcggtggtgt 60tggctcccgt at 727372DNAArtificial Sequencechemically synthesized 73atacgggagc caacaccatc taactgatgt gttgcgaagg gtctgctgtg tgatagagca 60ggtgtgacgg at 727472DNAArtificial Sequencechemically synthesized 74atccgtcaca cctgctctat cacacagcag acccttcgca acacatcagt tagatggtgt 60tggctcccgt at 727572DNAArtificial Sequencechemically synthesized 75atacgggagc caacaccagg cgggagaata gatagagtta gtcgtagtta gagcagagca 60ggtgtgacgg at 727672DNAArtificial Sequencechemically synthesized 76atccgtcaca cctgctctgc tctaactacg actaactcta tctattctcc cgcctggtgt 60tggctcccgt at 727772DNAArtificial Sequencechemically synthesized 77atacgggagc caacaccaga agaaccgcta aagcctatga ggaaaggatc atgcagagca 60ggtgtgacgg at 727872DNAArtificial Sequencechemically synthesized 78atccgtcaca cctgctctgc atgatccttt cctcataggc tttagcggtt cttctggtgt 60tggctcccgt at 727972DNAArtificial Sequencechemically synthesized 79atacgggagc caacaccagc cacgtcgaac cgggtgtcca tatacgtaat atgcagagca 60ggtgtgacgg at 728072DNAArtificial Sequencechemically synthesized 80atccgtcaca cctgctctgc atattacgta tatggacacc cggttcgacg tggctggtgt 60tggctcccgt at 728172DNAArtificial Sequencechemically synthesized 81atacgggagc caacaccatg ccatgtaccg gtacctactc tatcaggata taggagagca 60ggtgtgacgg at 728272DNAArtificial Sequencechemically synthesized 82atccgtcaca cctgctctcc tatatcctga tagagtaggt accggtacat ggcatggtgt 60tggctcccgt at 728372DNAArtificial Sequencechemically synthesized 83atacgggagc caacaccaga gtattccgct cacctatcgc caccatgtac accaagagca 60ggtgtgacgg at 728472DNAArtificial Sequencechemically synthesized 84atccgtcaca cctgctcttg gtgtacatgg tggcgatagg tgagcggaat actctggtgt 60tggctcccgt at 728572DNAArtificial Sequencechemically synthesized 85atacgggagc caacaccaac attgagagtg tggacatagt ggaacgcgaa cctgagagca 60ggtgtgacgg at 728672DNAArtificial Sequencechemically synthesized 86atccgtcaca cctgctctca ggttcgcgtt ccactatgtc cacactctca atgttggtgt 60tggctcccgt

at 728772DNAArtificial Sequencechemically synthesized 87atacgggagc caacaccaag cgacaaggaa gaattatcaa ggtacgaacc ggatagagca 60ggtgtgacgg at 728872DNAArtificial Sequencechemically synthesized 88atccgtcaca cctgctctat ccggttcgta ccttgataat tcttccttgt cgcttggtgt 60tggctcccgt at 728972DNAArtificial Sequencechemically synthesized 89atacgggagc caacaccatg tcatcatata ccaacactgg cgcggatagt ccagagagca 60ggtgtgacgg at 729072DNAArtificial Sequencechemically synthesized 90atccgtcaca cctgctctct ggactatccg cgccagtgtt ggtatatgat gacatggtgt 60tggctcccgt at 729172DNAArtificial Sequencechemically synthesized 91atacgggagc caacaccagc ctcgtgattt gatgaagttt cttgatctgc acgtagagca 60ggtgtgacgg at 729272DNAArtificial Sequencechemically synthesized 92atccgtcaca cctgctctac gtgcagatca agaaacttca tcaaatcacg aggctggtgt 60tggctcccgt at 729372DNAArtificial Sequencechemically synthesized 93atacgggagc caacaccatc gatgaacggc tcaccctcgt ccctatataa cactagagca 60ggtgtgacgg at 729472DNAArtificial Sequencechemically synthesized 94atccgtcaca cctgctctag tgttatatag ggacgagggt gagccgttca tcgatggtgt 60tggctcccgt at 729572DNAArtificial Sequencechemically synthesized 95atacgggagc caacaccaaa ggacacaaga agcttgaatc tccagttagt ggggagagca 60ggtgtgacgg at 729672DNAArtificial Sequencechemically synthesized 96atccgtcaca cctgctctcc ccactaactg gagattcaag cttcttgtgt cctttggtgt 60tggctcccgt at 729772DNAArtificial Sequencechemically synthesized 97atacgggagc caacaccacg ctccccgaga tcacgtacgc tcgccccaga ctggagagca 60ggtgtgacgg at 729872DNAArtificial Sequencechemically synthesized 98atccgtcaca cctgctctcc agtctggggc gagcgtacgt gatctcgggg agcgtggtgt 60tggctcccgt at 729972DNAArtificial Sequencechemically synthesized 99atacgggagc caacaccatg gctcaccagg accattattt tcagctcccc cgccagagca 60ggtgtgacgg at 7210072DNAArtificial Sequencechemically synthesized 100atccgtcaca cctgctctgg cgggggagct gaaaataatg gtcctggtga gccatggtgt 60tggctcccgt at 7210172DNAArtificial Sequencechemically synthesized 101atacgggagc caacaccagt gcaccaaata aaaagctgtc ccagactcga gcgaagagca 60ggtgtgacgg at 7210272DNAArtificial Sequencechemically synthesized 102atccgtcaca cctgctcttc gctcgagtct gggacagctt tttatttggt gcactggtgt 60tggctcccgt at 7210372DNAArtificial Sequencechemically synthesized 103atacgggagc caacaccaat cgtgtcacaa tggcatatcc tacgtcataa gccaagagca 60ggtgtgacgg at 7210472DNAArtificial Sequencechemically synthesized 104atccgtcaca cctgctcttg gcttatgacg taggatatgc cattgtgaca cgattggtgt 60tggctcccgt at 7210572DNAArtificial Sequencechemically synthesized 105atacgggagc caacaccata ataccagccg acagccttgg tgctatgatt tgacagagca 60ggtgtgacgg at 7210672DNAArtificial Sequencechemically synthesized 106atccgtcaca cctgctctgt caaatcatag caccaaggct gtcggctggt attatggtgt 60tggctcccgt at 7210772DNAArtificial Sequencechemically synthesized 107atacgggagc caacaccatc gagtgcgtgg aactcaaggg cacaatagct acacagagca 60ggtgtgacgg at 7210872DNAArtificial Sequencechemically synthesized 108atccgtcaca cctgctctgt gtagctattg tgcccttgag ttccacgcac tcgatggtgt 60tggctcccgt at 7210972DNAArtificial Sequencechemically synthesized 109atacgggagc caacaccaca tagtccctgt cgcacccctc ccgtgaccgt tatcagagca 60ggtgtgacgg at 7211072DNAArtificial Sequencechemically synthesized 110atccgtcaca cctgctctga taacggtcac gggaggggtg cgacagggac tatgtggtgt 60tggctcccgt at 7211172DNAArtificial Sequencechemically synthesized 111atacgggagc caacaccagg cgttctagag accactctta ataaccttga tgtgagagca 60ggtgtgacgg at 7211272DNAArtificial Sequencechemically synthesized 112atccgtcaca cctgctctca catcaaggtt attaagagtg gtctctagaa cgcctggtgt 60tggctcccgt at 7211372DNAArtificial Sequencechemically synthesized 113atacgggagc caacaccagt ttctcagtat ataagatatt tcatcgcagg tagaagagca 60ggtgtgacgg at 7211472DNAArtificial Sequencechemically synthesized 114atccgtcaca cctgctcttc tacctgcgat gaaatatctt atatactgag aaactggtgt 60tggctcccgt at 7211572DNAArtificial Sequencechemically synthesized 115atacgggagc caacaccaat gtgacagtcg cgactcctgt cgtttgcata gggtagagca 60ggtgtgacgg at 7211672DNAArtificial Sequencechemically synthesized 116atccgtcaca cctgctctac cctatgcaaa cgacaggagt cgcgactgtc acattggtgt 60tggctcccgt at 7211772DNAArtificial Sequencechemically synthesized 117atacgggagc caacaccaaa aaatcaacat ggtgaaacat tcgaatgcag ttgaagagca 60ggtgtgacgg at 7211872DNAArtificial Sequencechemically synthesized 118atccgtcaca cctgctcttc aactgcattc gaatgtttca ccatgttgat tttttggtgt 60tggctcccgt at 7211972DNAArtificial Sequencechemically synthesized 119atacgggagc caacaccatg cgcggctcat agactgtaac ccggatggga acctagagca 60ggtgtgacgg at 7212072DNAArtificial Sequencechemically synthesized 120atccgtcaca cctgctctag gttcccatcc gggttacagt ctatgagccg cgcatggtgt 60tggctcccgt at 7212172DNAArtificial Sequencechemically synthesized 121atacgggagc caacaccaag tcccgttacc aaacagaacc atggagagcg atggagagca 60ggtgtgacgg at 7212272DNAArtificial Sequencechemically synthesized 122atccgtcaca cctgctctcc atcgctctcc atggttctgt ttggtaacgg gacttggtgt 60tggctcccgt at 7212372DNAArtificial Sequencechemically synthesized 123atacgggagc caacaccatt gacccgagac tccagctgag tgacacctga tgtgagagca 60ggtgtgacgg at 7212472DNAArtificial Sequencechemically synthesized 124atccgtcaca cctgctctca catcaggtgt cactcagctg gagtctcggg tcaatggtgt 60tggctcccgt at 7212572DNAArtificial Sequencechemically synthesized 125atacgggagc caacaccagt gacaccaaac catgctcagg ccattcggtt atatagagca 60ggtgtgacgg at 7212672DNAArtificial Sequencechemically synthesized 126atccgtcaca cctgctctat ataaccgaat ggcctgagca tggtttggtg tcactggtgt 60tggctcccgt at 7212772DNAArtificial Sequencechemically synthesized 127atacgggagc caacaccagc caacggacac caggttgatc aatccccagt cctgagagca 60ggtgtgacgg at 7212872DNAArtificial Sequencechemically synthesized 128atccgtcaca cctgctctca ggactgggga ttgatcaacc tggtgtccgt tggctggtgt 60tggctcccgt at 7212972DNAArtificial Sequencechemically synthesized 129atacgggagc caacaccagc cctaccgtac cccctcaaga cagaacctgc atcaagagca 60ggtgtgacgg at 7213072DNAArtificial Sequencechemically synthesized 130atccgtcaca cctgctcttg atgcaggttc tgtcttgagg gggtacggta gggctggtgt 60tggctcccgt at 7213172DNAArtificial Sequencechemically synthesized 131atacgggagc caacaccact agacaaggtc aaaccgcata tggacccgtg ctatagagca 60ggtgtgacgg at 7213272DNAArtificial Sequencechemically synthesized 132atccgtcaca cctgctctat agcacgggtc catatgcggt ttgaccttgt ctagtggtgt 60tggctcccgt at 7213372DNAArtificial Sequencechemically synthesized 133atacgggagc caacaccaca acatgagctg aatctgtccc taatgcgtgt gcatagagca 60ggtgtgacgg at 7213472DNAArtificial Sequencechemically synthesized 134atccgtcaca cctgctctat gcacacgcat tagggacaga ttcagctcat gttgtggtgt 60tggctcccgt at 7213572DNAArtificial Sequencechemically synthesized 135atacgggagc caacaccacg gtgaagcatg gcaatattaa ccatgatcac cttcagagca 60ggtgtgacgg at 7213672DNAArtificial Sequencechemically synthesized 136atccgtcaca cctgctctga aggtgatcat ggttaatatt gccatgcttc accgtggtgt 60tggctcccgt at 7213772DNAArtificial Sequencechemically synthesized 137atacgggagc caacaccacc acttgtcacg accgtgtctc tgtggcgctt ggggagagca 60ggtgtgacgg at 7213872DNAArtificial Sequencechemically synthesized 138atccgtcaca cctgctctcc ccaagcgcca cagagacacg gtcgtgacaa gtggtggtgt 60tggctcccgt at 7213972DNAArtificial Sequencechemically synthesized 139atacgggagc caacaccata tagccgcgcc tgtgagtttt gtgggagcaa gagtagagca 60ggtgtgacgg at 7214072DNAArtificial Sequencechemically synthesized 140atccgtcaca cctgctctac tcttgctccc acaaaactca caggcgcggc tatatggtgt 60tggctcccgt at 7214172DNAArtificial Sequencechemically synthesized 141atacgggagc caacaccagc tacagtgtca gacggttcca ccttaacctc gtcaagagca 60ggtgtgacgg at 7214272DNAArtificial Sequencechemically synthesized 142atccgtcaca cctgctcttg acgaggttaa ggtggaaccg tctgacactg tagctggtgt 60tggctcccgt at 7214372DNAArtificial Sequencechemically synthesized 143atacgggagc caacaccatt gactaagcga ttagtcccac aggtgaccgg ggagagagca 60ggtgtgacgg at 7214472DNAArtificial Sequencechemically synthesized 144atccgtcaca cctgctctct tcccggnctc ctgtgtgatt aatctgttat tctatggtgt 60tggctcccgt at 7214572DNAArtificial Sequencechemically synthesized 145atacgggagc caacaccaat tctaacacag gtttctccgt ttcgttagct gctaagagca 60ggtgtgacgg at 7214672DNAArtificial Sequencechemically synthesized 146atccgtcaca cctgctctta gcagctaacg aaacggagaa acctgtgtta gaattggtgt 60tggctcccgt at 7214772DNAArtificial Sequencechemically synthesized 147atacgggagc caacaccact catcccgttg gaacacttta atatggccca ctctagagca 60ggtgtgacgg at 7214872DNAArtificial Sequencechemically synthesized 148atccgtcaca cctgctctag agtgggccat attaaagtgt tccaacggga tgagtggtgt 60tggctcccgt at 7214972DNAArtificial Sequencechemically synthesized 149atacgggagc caacaccact actgtgcaga tccagcatct acggtgaaat ttgcagagca 60ggtgtgacgg at 7215072DNAArtificial Sequencechemically synthesized 150atccgtcaca cctgctctgc aaatttcacc gtagatgctg gatctgcaca gtagtggtgt 60tggctcccgt at 7215172DNAArtificial Sequencechemically synthesized 151atacgggagc caacaccatg cggaaagccc ataccaaccc agaagccagc gctaagagca 60ggtgtgacgg at 7215272DNAArtificial Sequencechemically synthesized 152atccgtcaca cctgctctta gcgctggctt ctgggttggt atgggctttc cgcatggtgt 60tggctcccgt at 7215372DNAArtificial Sequencechemically synthesized 153atacgggagc caacaccagc caactagcct gaaacccata attatacagc ttagagagca 60ggtgtgacgg at 7215472DNAArtificial Sequencechemically synthesized 154atccgtcaca cctgctctct aagctgtata attatgggtt tcaggctagt tggctggtgt 60tggctcccgt at 7215572DNAArtificial Sequencechemically synthesized 155atacgggagc caacaccact gtatccgttg atgacaaaca gtcgcagccc acttagagca 60ggtgtgacgg at 7215672DNAArtificial Sequencechemically synthesized 156atccgtcaca cctgctctcc tcgactcgat ttcacttagt ctaacactaa ttggtggtgt 60tggctcccgt at 7215772DNAArtificial Sequencechemically synthesized 157atacgggagc caacaccaag gtaatgaagg gggaaaatgg agttttgccc ttaaagagca 60ggtgtgacgg at 7215872DNAArtificial Sequencechemically synthesized 158atccgtcaca cctgctcttt aagggcaaaa ctccattttc ccccttcatt accttggtgt 60tggctcccgt at 7215972DNAArtificial Sequencechemically synthesized 159atacgggagc caacaccaag ctcgtagaag catcttacgc ggcgcccttg caccagagca 60ggtgtgacgg at 7216072DNAArtificial Sequencechemically synthesized 160atccgtcaca cctgctctgg tgcaagggcg ccgcgtaaga tgcttctacg agcttggtgt 60tggctcccgt at 7216172DNAArtificial Sequencechemically synthesized 161atacgggagc caacaccacg atcattgaca tacttctcta tcccgtctgt ctgtagagca 60ggtgtgacgg at 7216272DNAArtificial Sequencechemically synthesized 162atccgtcaca cctgctctac agacagacgg gatagagaag tatgtcaatg atcgtggtgt 60tggctcccgt at 7216372DNAArtificial Sequencechemically synthesized 163atacgggagc caacaccacc acagagtcta cccaaggcag gctgtcaatc aacaagagca 60ggtgtgacgg at 7216472DNAArtificial Sequencechemically synthesized 164atccgtcaca cctgctcttg ttgattgaca gcctgccttg ggtagactct gtggtggtgt 60tggctcccgt at 7216572DNAArtificial Sequencechemically synthesized 165atacgggagc caacaccagg ctacgacaaa ggctatgaca tgaatgggtc aactagagca 60ggtgtgacgg at 7216672DNAArtificial Sequencechemically synthesized 166atccgtcaca cctgctctag ttgacccatt catgtcatag cctttgtcgt agcctggtgt 60tggctcccgt at 7216772DNAArtificial Sequencechemically synthesized 167atacgggagc caacaccagg gccggagggt tcttcttgag ccttttcgcc aggcagagca 60ggtgtgacgg at 7216872DNAArtificial Sequencechemically synthesized 168atccgtcaca cctgctctgc ctggcgaaaa ggctcaagaa gaaccctccg gccctggtgt 60tggctcccgt at 7216972DNAArtificial Sequencechemically synthesized 169atacgggagc caacaccaaa tgtcttggaa ggcagatatc ggaacgagtg gaccagagca 60ggtgtgacgg at 7217072DNAArtificial Sequencechemically synthesized 170atccgtcaca

cctgctctgg tccactcgtt ccgatatctg ccttccaaga catttggtgt 60tggctcccgt at 7217172DNAArtificial Sequencechemically synthesized 171atacgggagc caacaccaga cactcaggta tggagcactc gatccacgcg tgtgagagca 60ggtgtgacgg at 7217272DNAArtificial Sequencechemically synthesized 172atccgtcaca cctgctctca cacgcgtgga tcgagtgctc catacctgag tgtctggtgt 60tggctcccgt at 7217372DNAArtificial Sequencechemically synthesized 173atacgggagc caacaccatc cgcgaccaga atctgtaaag gcgttagata tgccagagca 60ggtgtgacgg at 7217472DNAArtificial Sequencechemically synthesized 174atccgtcaca cctgctctgg catatctaac gcctttacag attctggtcg cggatggtgt 60tggctcccgt at 7217572DNAArtificial Sequencechemically synthesized 175atacgggagc caacaccact caacgtaacg ggtggagacc ctcacatcga tatgagagca 60ggtgtgacgg at 7217672DNAArtificial Sequencechemically synthesized 176atccgtcaca cctgctctca tatcgatgtg agggtctcca cccgttacgt tgagtggtgt 60tggctcccgt at 7217772DNAArtificial Sequencechemically synthesized 177atacgggagc caacaccaga tggtgaccgg attacgagaa ccagagctga tagaagagca 60ggtgtgacgg at 7217872DNAArtificial Sequencechemically synthesized 178atccgtcaca cctgctcttc tatcagctct ggttctcgta atccggtcac catctggtgt 60tggctcccgt at 7217972DNAArtificial Sequencechemically synthesized 179atacgggagc caacaccaaa ccagggaata cacagcaaaa ctacggtgtc ctgtagagca 60ggtgtgacgg at 7218072DNAArtificial Sequencechemically synthesized 180atccgtcaca cctgctctac aggacaccgt agttttgctg tgtattccct ggtttggtgt 60tggctcccgt at 7218172DNAArtificial Sequencechemically synthesized 181atacgggagc caacaccagc cgataaagaa cgcagctaat ttgctctccc gagcagagca 60ggtgtgacgg at 7218272DNAArtificial Sequencechemically synthesized 182atccgtcaca cctgctctgc tcgggagagc aaattagctg cgttctttat cggctggtgt 60tggctcccgt at 7218372DNAArtificial Sequencechemically synthesized 183atacgggagc caacaccagc atatgtagtg aagcgacata caccggggca acgtagagca 60ggtgtgacgg at 7218472DNAArtificial Sequencechemically synthesized 184atccgtcaca cctgctctac gttgccccgg tgtatgtcgc ttcactacat atgctggtgt 60tggctcccgt at 7218572DNAArtificial Sequencechemically synthesized 185atacgggagc caacaccacc gaactaagag gaaagtctcg gagtgcggct agttagagca 60ggtgtgacgg at 7218672DNAArtificial Sequencechemically synthesized 186atccgtcaca cctgctctaa ctagccgcac tccgagactt tcctcttagt tcggtggtgt 60tggctcccgt at 7218772DNAArtificial Sequencechemically synthesized 187atacgggagc caacaccaag gccacccagt taatgcagtc tcgttatgtt ctgtagagca 60ggtgtgacgg at 7218872DNAArtificial Sequencechemically synthesized 188atccgtcaca cctgctctac agaacataac gagactgcat taactgggtg gccttggtgt 60tggctcccgt at 7218972DNAArtificial Sequencechemically synthesized 189atacgggagc caacaccaat accatacctg acttatgacc tgatcatacc agtgagagca 60ggtgtgacgg at 7219072DNAArtificial Sequencechemically synthesized 190atccgtcaca cctgctctca ctggtatgat caggtcataa gtcaggtatg gtattggtgt 60tggctcccgt at 7219171DNAArtificial Sequencechemically synthesized 191atacgggagc cagcaccaca gattcttcaa ctttgctgcc atattccaac aacagagcag 60gcgtgacgga t 7119271DNAArtificial Sequencechemically synthesized 192atccgtcacg cctgctctgt tgttggaata tggcagcaaa gttgaagaat ctgtggtgct 60ggctcccgta t 7119372DNAArtificial Sequencechemically synthesized 193atacgggagc caacaccaca tgccataatt ggaccctcat cgccccgtcg tcccagagca 60ggtgtgacgg at 7219472DNAArtificial Sequencechemically synthesized 194atccgtcaca cctgctctgg gacgacgggg cgatgagggt ccaattatgg catgtggtgt 60tggctcccgt at 7219572DNAArtificial Sequencechemically synthesized 195atacgggagc caacaccaaa ccgcaccagt cacacaccag ttcgcctcca tgttagagca 60ggtgtgacgg at 7219672DNAArtificial Sequencechemically synthesized 196atccgtcaca cctgctctaa catggaggcg aactggtgtg tgactggtgc ggtttggtgt 60tggctcccgt at 7219772DNAArtificial Sequencechemically synthesized 197atacgggagc caacaccatt ttacagtact aaagtatgtg atatgccgcg ccggagagca 60ggtgtgacgg at 7219872DNAArtificial Sequencechemically synthesized 198atccgtcaca cctgctctcc ggcgcggcat atcacatact ttagtactgt aaaatggtgt 60tggctcccgt at 7219972DNAArtificial Sequencechemically synthesized 199atacgggagc caacaccaaa agaacgcact actttcggaa tcgaatctat ccccagagca 60ggtgtgacgg at 7220072DNAArtificial Sequencechemically synthesized 200atccgtcaca cctgctctgg ggatagattc gattccgaaa gtagtgcgtt cttttggtgt 60tggctcccgt at 7220172DNAArtificial Sequencechemically synthesized 201atccgtcaca cctgctctag acgaatattg tatcctcatt agatcaaaaa cgggtggtgt 60tggctcccgt at 7220272DNAArtificial Sequencechemically synthesized 202atacgggagc caacaccagc ttttcctaga atgattttct ttagctacct gagaagagca 60ggtgtgacgg at 7220372DNAArtificial Sequencechemically synthesized 203atccgtcaca cctgctcttc tcaggtagct aaagaaaatc attctaggaa aagctggtgt 60tggctcccgt at 7220458DNAArtificial Sequencechemically synthesized 204atacgggagc caacaccacg cttagatatt atccttgtcc agagcaggtg tgacggat 5820558DNAArtificial Sequencechemically synthesized 205atccgtcaca cctgctctgg acaaggataa tatctaagcg tggtgttggc tcccgtat 5820672DNAArtificial Sequencechemically synthesized 206acacgggagc caacaccatc catagctcat ctataccctc ttccgagtcc caccagagca 60ggtgtgacgg at 7220772DNAArtificial Sequencechemically synthesized 207atccgtcaca cctgctctgg tgggactcgg aagagggtat agatgagcta tggatggtgt 60tggctcccgt gt 7220872DNAArtificial Sequencechemically synthesized 208atacgggagc caacaccacc ctacaccagc gccctacact tttgtagcac ttcgagagca 60ggtgtgacgg at 7220972DNAArtificial Sequencechemically synthesized 209atccgtcaca cctgctctcg aagtgctaca aaagtgtagg gcgctggtgt agggtggtgt 60tggctcccgt at 7221069DNAArtificial Sequencechemically synthesized 210atacgggagc caacaccata gtgttgggcc aatacggtaa cgtgtccttg gagagcaggt 60gtgacggat 6921169DNAArtificial Sequencechemically synthesized 211atccgtcaca cctgctctcc aaggacacgt taccgtattg gcccaacact atggtgttgg 60ctcccgtat 6921272DNAArtificial Sequencechemically synthesized 212atacgggagc caacaccacc cgtttttgat ctaatgagga tacaatattc gtctagagca 60ggtgtgacgg at 7221372DNAArtificial Sequencechemically synthesized 213atacgggagc caacaccact atcaatttgt tggcgacact tcaacccaca cgttagagca 60ggtgtgacgg at 7221472DNAArtificial Sequencechemically synthesized 214atccgtcaca cctgctctaa cgtgtgggtt gaagtgtcgc caacaaattg atagtggtgt 60tggctcccgt at 7221572DNAArtificial Sequencechemically synthesized 215atacgggagc caacaccatc agcatgggtt agagctgggg gaaatatttg gtcgagagca 60ggtgtgacgg at 7221672DNAArtificial Sequencechemically synthesized 216atccgtcaca cctgctctcg accaaatatt tcccccagct ctaacccatg ctgatggtgt 60tggctcccgt at 7221769DNAArtificial Sequencechemically synthesized 217atacgggagc caacaccata gtgttgggcc aatacggtaa cgtgtccttg gagagcaggt 60gtgacggat 6921869DNAArtificial Sequencechemically synthesized 218atccgtcaca cctgctctcc aaggacacgt taccgtattg gcccaacact atggtgttgg 60ctcccgtat 6921972DNAArtificial Sequencechemically synthesized 219atacgggagc caacaccaac aaaacaacag gaatatcgtt cccaagcgga ccccagagca 60ggtgtgacgg at 7222072DNAArtificial Sequencechemically synthesized 220atccgtcaca cctgctctgg ggtccgcttg ggaacgatat tcctgttgtt ttgttggtgt 60tggctcccgt at 7222172DNAArtificial Sequencechemically synthesized 221atacgggagc caacaccata caaagtgttg ttagatttaa cccatgttgc catcagagca 60ggtgtgacgg at 7222272DNAArtificial Sequencechemically synthesized 222atccgtcaca cctgctctga tggcaacatg ggttaaatct aacaacactt tgtatggtgt 60tggctcccgt at 7222372DNAArtificial Sequencechemically synthesized 223atacgggagc caacaccaag ggtgttcaca ctggcaggcg acgccctcgt gttgagagca 60ggtgtgacgg at 7222473DNAArtificial Sequencechemically synthesized 224atccgtcaca cctgctctca acacgagggc gtcgcctgcc agtgtgaaca cccttggtgt 60tggctcccgt atn 7322572DNAArtificial Sequencechemically synthesized 225atacgggagc caacaccaca atagtcgatt agtaatgatc cacacattgg tcggagagca 60ggtgtgacgg at 7222672DNAArtificial Sequencechemically synthesized 226atccgtcaca cctgctctcc gaccaatgtg tggatcatta ctaatcgact attgtggtgt 60tggctcccgt at 7222769DNAArtificial Sequencechemically synthesized 227atacgggagc caacaccata gttttgggcc aatacggtaa cgtgtccttg gagagcaggt 60gtgacggat 6922869DNAArtificial Sequencechemically synthesized 228atccgtcaca cctgctctcc aaggacacgt taccgtattg gcccaaaact atggtgttgg 60ctcccgtat 6922969DNAArtificial Sequencechemically synthesized 229atacgggagc caacaccata gtgctggacc aatacggtaa cgtgtccttg gagagcaggt 60gtgacggat 6923069DNAArtificial Sequencechemically synthesized 230atccgtcaca cctgctctcc aaggacacgt taccgtattg gtccagcact atggtgttgg 60ctcccgtat 6923158DNAArtificial Sequencechemically synthesized 231atacgggagc caacaccacg attagcaatg aattatctac agagcaggtg tgacggat 5823258DNAArtificial Sequencechemically synthesized 232atccgtcaca cctgctctgt agataattca ttgctaatcg tggtgttggc tcccgtat 5823372DNAArtificial Sequencechemically synthesized 233atacgggagc caacaccaat tctaacacag gtttctccgt ttcgttagct gctaagagca 60ggtgtgacgg at 7223472DNAArtificial Sequencechemically synthesized 234atccgtcaca cctgctctta gcagctaacg aaacggagaa acctgtgtta gaattggtgt 60tggctcccgt at 7223572DNAArtificial Sequencechemically synthesized 235atacgggagc caacaccatt ctatcgttcc ggacgcttat gccttgccat ctacagagca 60ggtgtgacgg at 7223672DNAArtificial Sequencechemically synthesized 236atccgtcaca cctgctctgt agatggcaag gcataagcgt ccggaacgat agaatggtgt 60tggctcccgt at 7223772DNAArtificial Sequencechemically synthesized 237atacgggagc caacaccaac tgactcagtc tgctggtggg ctatattttt gcggagagca 60ggtgtgacgg at 7223872DNAArtificial Sequencechemically synthesized 238atccgtcaca cctgctctcc gcaaaaatat agcccaccag cagactgagt cagttggtgt 60tggctcccgt at 7223972DNAArtificial Sequencechemically synthesized 239atacgggagc caacaccaga ccgggcggta aaataacaaa ttacatcccc accgagagca 60ggtgtgacgg at 7224072DNAArtificial Sequencechemically synthesized 240atccgtcaca cctgctctcg gtggggatgt aatttgttat tttaccgccc ggtctggtgt 60tggctcccgt at 7224172DNAArtificial Sequencechemically synthesized 241atacgggagc caacaccaat gaccatatca aaccacaccg gccccccact gatgagagca 60ggtgtgacgg at 7224272DNAArtificial Sequencechemically synthesized 242atccgtcaca cctgctctca tcagtggggg gccggtgtgg tttgatatgg tcattggtgt 60tggctcccgt at 7224372DNAArtificial Sequencechemically synthesized 243atacgggagc caacaccaat gaccatatca aaccacaccg gccccccact gatgagagca 60ggtgtgacgg at 7224472DNAArtificial Sequencechemically synthesized 244atccgtcaca cctgctctca tcagtggggg gccggtgtgg tttgatatgg tcattggtgt 60tggctcccgt at 7224572DNAArtificial Sequencechemically synthesized 245atacgggagc caacaccact caagtccaga tcacactcgt gctgctaccg gttcagagca 60ggtgtgacgg at 7224672DNAArtificial Sequencechemically synthesized 246atccgtcaca cctgctctga accggtagca gcacgagtgt gatctggact tgagtggtgt 60tggctcccgt at 7224772DNAArtificial Sequencechemically synthesized 247atacgggagc caacaccatt tctaactaat cgagtcggta ccactgggcc cctgagagca 60ggtgtgacgg at 7224872DNAArtificial Sequencechemically synthesized 248atccgtcaca cctgctctca ggggcccagt ggtaccgact cgattagtta gaaatggtgt 60tggctcccgt at 7224972DNAArtificial Sequencechemically synthesized 249atacgggagc caacaccatg gctaggaaat aatgtccatc ggcacatcct cccgagagca 60ggtgtgacgg at 7225072DNAArtificial Sequencechemically synthesized 250atccgtcaca cctgctctcg ggaggatgtg ccgatggaca ttatttccta gccatggtgt 60tggctcccgt at 7225172DNAArtificial Sequencechemically synthesized 251atacgggagc caacaccaac cgtacaaaca agctagtgtg gttaatactg cataagagca 60ggtgtgacgg at 7225272DNAArtificial Sequencechemically synthesized 252atccgtcaca cctgctctta tgcagtatta accacactag cttgtttgta cggttggtgt 60tggctcccgt at 7225372DNAArtificial Sequencechemically synthesized 253atacgggagc caacaccaga ggctaccggt aaatgggata tcattgcgtt tgcaagagca 60ggtgtgacgg at 7225472DNAArtificial Sequencechemically synthesized 254atccgtcaca cctgctcttg caaacgcaat gatatcccat ttaccggtag cctctggtgt 60tggctcccgt at 7225572DNAArtificial Sequencechemically synthesized 255atacgggagc

caacaccact caaagggtta ccaatccgtt ggacacagta ctgtagagca 60ggtgtgacgg at 7225672DNAArtificial Sequencechemically synthesized 256atccgtcaca cctgctctac agtactgtgt ccaacggatt ggtaaccctt tgagtggtgt 60tggctcccgt at 7225772DNAArtificial Sequencechemically synthesized 257atacgggagc caacaccatg aacatacaag aggtagacct ggtagtcgta ttctagagca 60ggtgtgacgg at 7225872DNAArtificial Sequencechemically synthesized 258atccgtcaca cctgctctag aatacgacta ccaggtctac ctcttgtatg ttcatggtgt 60tggctcccgt at 7225972DNAArtificial Sequencechemically synthesized 259atacgggagc caacaccatc tgagccgtaa ttggttattt tccagtgaag tgcgagagca 60ggtgtgacgg at 7226072DNAArtificial Sequencechemically synthesized 260atccgtcaca cctgctctcg cacttcactg gaaaataacc aattacggct cagatggtgt 60tggctcccgt at 7226172DNAArtificial Sequencechemically synthesized 261atacgggagc caacaccatg actacgtggg caagacatcc cgcgcgtcca tcccagagca 60ggtgtgacgg at 7226272DNAArtificial Sequencechemically synthesized 262atccgtcaca cctgctctgg gatggacgcg cgggatgtct tgcccacgta gtcatggtgt 60tggctcccgt at 7226371DNAArtificial Sequencechemically synthesized 263atacgggagc caacaccaac atggcgtggc aggtaatcta acctccctac ccaagagcag 60gtgtgacgga t 7126471DNAArtificial Sequencechemically synthesized 264atccgtcaca cctgctcttg ggtagggagg ttagattacc tgccacgcca tgttggtgtt 60ggctcccgta t 7126572DNAArtificial Sequencechemically synthesized 265atacgggagc caacaccaca cgacccaagg aattggaaaa acaccgacat tccaagagca 60ggtgtgacgg at 7226672DNAArtificial Sequencechemically synthesized 266atccgtcaca cctgctcttg gaatgtcggt gtttttccaa ttccttgggt cgtgtggtgt 60tggctcccgt at 7226772DNAArtificial Sequencechemically synthesized 267atacgggagc caacaccaag actgataacc ttacgtccag taggggcaag ctatagagca 60ggtgtgacgg at 7226872DNAArtificial Sequencechemically synthesized 268atccgtcaca cctgctctat agcttgcccc tactggacgt aaggttatca gtcttggtgt 60tggctcccgt at 7226972DNAArtificial Sequencechemically synthesized 269atacgggagc caacaccaat aaccgttttc ggccatgaga atactgtcac ttacagagca 60ggtgtgacgg at 7227072DNAArtificial Sequencechemically synthesized 270atccgtcaca cctgctctgt aagtgacagt attctcatgg ccgaaaacgg ttattggtgt 60tggctcccgt at 7227172DNAArtificial Sequencechemically synthesized 271atacgggagc caacaccaag acgaatagct cactacctcg tgaactatcc cctgagagca 60ggtgtgacgg at 7227272DNAArtificial Sequencechemically synthesized 272atccgtcaca cctgctctca ggggatagtt cacgaggtag tgagctattc gtcttggtgt 60tggctcccgt at 7227372DNAArtificial Sequencechemically synthesized 273atacgggagc caacaccata caggatctat tcccagaaga gttggcatat accaagagca 60ggtgtgacgg at 7227472DNAArtificial Sequencechemically synthesized 274atccgtcaca cctgctcttg gtatatgcca actcttctgg gaatagatcc tgtatggtgt 60tggctcccgt at 7227572DNAArtificial Sequencechemically synthesized 275atacgggagc caacaccatg gagaacattt ccatgttggc gaccatgggc ctcgagagca 60ggtgtgacgg at 7227672DNAArtificial Sequencechemically synthesized 276atccgtcaca cctgctctcg aggcccatgg tcgccaacat ggaaatgttc tccatggtgt 60tggctcccgt at 7227772DNAArtificial Sequencechemically synthesized 277atacgggagc caacaccagt acgaattata ctacagaggg cgtccgcgtt ggggagagca 60ggtgtgacgg at 7227872DNAArtificial Sequencechemically synthesized 278atccgtcaca cctgctctcc ccaacgcgga cgccctctgt agtataattc gtactggtgt 60tggctcccgt at 7227972DNAArtificial Sequencechemically synthesized 279atacgggagc caacaccacg caacctacct ctcacggctg ttcatgacgg acttagagca 60ggtgtgacgg at 7228072DNAArtificial Sequencechemically synthesized 280atccgtcaca cctgctctaa gtccgtcatg aacagccgtg agaggtaggt tgcgtggtgt 60tggctcccgt at 7228172DNAArtificial Sequencechemically synthesized 281atacgggagc caacaccatg ccaggcaagt cattgtgagt atagaatcac ctttagagca 60ggtgtgacgg at 7228272DNAArtificial Sequencechemically synthesized 282atccgtcaca cctgctctaa aggtgattct atactcacaa tgacttgcct ggcatggtgt 60tggctcccgt at 7228372DNAArtificial Sequencechemically synthesized 283atacgggagc caacaccagg accgtcgatg attgcaggtg cgtggtaaat acgcagagca 60ggtgtgacgg at 7228472DNAArtificial Sequencechemically synthesized 284atccgtcaca cctgctctgc gtatttacca cgcacctgca atcatcgacg gtcctggtgt 60tggctcccgt at 7228572DNAArtificial Sequencechemically synthesized 285atacgggagc caacaccatg ctacatcggt cagaagatcc gagcctgccc gcgtagagca 60ggtgtgacgg at 7228672DNAArtificial Sequencechemically synthesized 286atccgtcaca cctgctctac gcgggcaggc tcggatcttc tgaccgatgt agcatggtgt 60tggctcccgt at 7228772DNAArtificial Sequencechemically synthesized 287atacgggagc caacaccaac tgggaaacgt tgatcgtagc tgagtgatag tgctagagca 60ggtgtgacgg at 7228872DNAArtificial Sequencechemically synthesized 288atccgtcaca cctgctctag cactatcact cagctacgat caacgtttcc cagttggtgt 60tggctcccgt at 7228972DNAArtificial Sequencechemically synthesized 289atacgggagc caacaccaat gtttgaagca aagccgaggc atgtagaaac gtctagagca 60ggtgtgacgg at 7229072DNAArtificial Sequencechemically synthesized 290atccgtcaca cctgctctag acgtttctac atgcctcggc tttgcttcaa acattggtgt 60tggctcccgt at 7229172DNAArtificial Sequencechemically synthesized 291atacgggagc caacaccaga gggggtcaaa aatgctagag aatacaccgt cagcagagca 60ggtgtgacgg at 7229272DNAArtificial Sequencechemically synthesized 292atccgtcaca cctgctctgc tgacggtgta ttctctagca tttttgaccc cctctggtgt 60tggctcccgt at 7229372DNAArtificial Sequencechemically synthesized 293atacgggagc caacaccaaa gcgagctcgg catgtcgacg gtgtgcgtcc accgagagca 60ggtgtgacgg at 7229472DNAArtificial Sequencechemically synthesized 294atccgtcaca cctgctctcg gtggacgcac accgtcgaca tgccgagctc gctttggtgt 60tggctcccgt at 7229572DNAArtificial Sequencechemically synthesized 295atacgggagc caacaccatt cccccctctc gttctgttgc cccgtatcct aattagagca 60ggtgtgacgg at 7229671DNAArtificial Sequencechemically synthesized 296atacgggagc caacaccagc cggatatccg atgtgcttgt ctgacctggt ccgagagcag 60gtgtgacgga t 7129772DNAArtificial Sequencechemically synthesized 297atacgggagc caacaccact gttatgttag ctcctcccta aactctttga ctcaagagca 60ggtgtgacgg at 7229872DNAArtificial Sequencechemically synthesized 298atacgggagc caacaccacc gcatgcgttc ccagcccgct gatgcattgt tgttagagca 60ggtgtgacgg at 7229972DNAArtificial Sequencechemically synthesized 299atacgggagc caacaccaga tcctgaaact atcactcctg cttataacct gttcagagca 60ggtgtgacgg at 7230071DNAArtificial Sequencechemically synthesized 300atacgggagc caacaccaac ccgggtgctg accactcggt ttgcgagccg ccgagagcag 60gtgtgacgga t 7130172DNAArtificial Sequencechemically synthesized 301atacgggagc caacaccact atgttttcac ggtcttgtgg attacgtctt gcgcagagca 60ggtgtgacgg at 7230270DNAArtificial Sequencechemically synthesized 302atacgggagc caacaccaga gcaggtgtga tggatatacg ggagccaaca ccagagcagg 60tgtgacggat 7030370DNAArtificial Sequencechemically synthesized 303atacgggagc caacaccaga gcaggtgtga tggatatacg ggagccaaca ccagagcagg 60tgtgacggat 7030470DNAArtificial Sequencechemically synthesized 304atacgggagc caacaccaga gcaggtgtga tggatatacg ggagccaaca ccagagcagg 60tgtgacggat 7030572DNAArtificial Sequencechemically synthesized 305atccgtcaca cctgctctgc acctgaagat caagtgtgag ttataggttg cgtttggtgt 60tggctcccgt at 7230672DNAArtificial Sequencechemically synthesized 306atacgggagc caacaccaat gcactcgtca cgcctttttt gctcttgcgc gttaagagca 60ggtgtgacgg at 7230771DNAArtificial Sequencechemically synthesized 307atacgggagc caacaccaac tggtctctac ggaaacctta cgccaatcta cacagagcag 60gtgtgacgga t 7130872DNAArtificial Sequencechemically synthesized 308atacgggagc caacaccatt agcaacgatt cccctgttag ttccggtgca tcccagagca 60ggtgtgacgg at 7230969DNAArtificial Sequencechemically synthesized 309atacgggagc caacaccaga gcaggtgtga ggtcgaattc cagcacactg gcggccgtta 60ctagtggat 6931072DNAArtificial Sequencechemically synthesized 310atccgtcaca cctgctctaa ttaggatacg gggcaacaga acgagagggg ggaatggtgt 60tggctcccgt at 7231171DNAArtificial Sequencechemically synthesized 311atccgtcaca cctgctctcg gaccaggtca gacaagcaca tcggatatcc ggctggtgtt 60ggctcccgta t 7131272DNAArtificial Sequencechemically synthesized 312atccgtcaca cctgctcttg agtcaaagag tttagggagg agctaacata acagtggtgt 60tggctcccgt at 7231372DNAArtificial Sequencechemically synthesized 313atccgtcaca cctgctctaa caacaatgca tcagcgggct gggaacgcat gcggtggtgt 60tggctcccgt at 7231472DNAArtificial Sequencechemically synthesized 314atccgtcaca cctgctctga acaggttata agcaggagtg atagtttcag gatctggtgt 60tggctcccgt at 7231571DNAArtificial Sequencechemically synthesized 315atccgtcaca cctgctctcg gcggctcgca aaccgagtgg tcagcacccg ggttggtgtt 60ggctcccgta t 7131672DNAArtificial Sequencechemically synthesized 316atccgtcaca cctgctctgc gcaagacgta atccacaaga ccgtgaaaac atagtggtgt 60tggctcccgt at 7231770DNAArtificial Sequencechemically synthesized 317atccgtcaca cctgctctgg tgttggctcc cgtatatcca tcacacctgc tctggtgttg 60gctcccgtat 7031870DNAArtificial Sequencechemically synthesized 318atccgtcaca cctgctctgg tgttggctcc cgtatatcca tcacacctgc tctggtgttg 60gctcccgtat 7031970DNAArtificial Sequencechemically synthesized 319atccgtcaca cctgctctgg tgttggctcc cgtatatcca tcacacctgc tctggtgttg 60gctcccgtat 7032072DNAArtificial Sequencechemically synthesized 320atccgtcaca cctgctctgc acctgaagat caagtgtgag ttataggttg cgtttggtgt 60tggctcccgt at 7232172DNAArtificial Sequencechemically synthesized 321atccgtcaca cctgctctta acgcgcaaga gcaaaaaagg cgtgacgagt gcattggtgt 60tggctcccgt at 7232271DNAArtificial Sequencechemically synthesized 322atccgtcaca cctgctctgt gtagattggc gtaaggtttc cgtagagacc agttggtgtt 60ggctcccgta t 7132372DNAArtificial Sequencechemically synthesized 323atccgtcaca cctgctctgg gatgcaccgg aactaacagg ggaatcgttg ctaatggtgt 60tggctcccgt at 7232469DNAArtificial Sequencechemically synthesized 324atccactagt aacggccgcc agtgtgctgg aattcgacct cacacctgct ctggtgttgg 60ctcccgtat 6932572DNAArtificial Sequencechemically synthesized 325atacgggagc caacaccagg gggatggccg cttgacattg acacgtacct gtggagagca 60ggtgtgacgg at 7232672DNAArtificial Sequencechemically synthesized 326atccgtcaca cctgctctcc acaggtacgt gtcaatgtca agcggccatc cccctggtgt 60tggctcccgt at 7232771DNAArtificial Sequencechemically synthesized 327atacgggagc caacaccaca agaggccgta cgaaaaaata actatgcaat tgtagagcag 60gtgtgacgga t 7132871DNAArtificial Sequencechemically synthesized 328atccgtcaca cctgctctac aattgcatag ttattttttc gtacggcctc ttgtggtgtt 60ggctcccgta t 7132972DNAArtificial Sequencechemically synthesized 329atacgggagc caacaccaaa ccaaggaaga ataaaacgat cgagtgatca caccagagca 60ggtgtgacgg at 7233072DNAArtificial Sequencechemically synthesized 330atccgtcaca cctgctctgg tgtgatcact cgatcgtttt attcttcctt ggtttggtgt 60tggctcccgt at 7233172DNAArtificial Sequencechemically synthesized 331atacgggagc caacaccaca agcggagcta gctgggtccg tggatccaag catgagagca 60ggtgtgacgg at 7233272DNAArtificial Sequencechemically synthesized 332atccgtcaca cctgctctca tgcttggatc cacggaccca gctagctccg cttgtggtgt 60tggctcccgt at 7233372DNAArtificial Sequencechemically synthesized 333atacgggagc caacaccatg gcacgcagaa aacgttaaag cagaatttcc tcagagagca 60ggtgtgacgg at 7233472DNAArtificial Sequencechemically synthesized 334atccgtcaca cctgctctct gaggaaattc tgctttaacg ttttctgcgt gccatggtgt 60tggctcccgt at 7233572DNAArtificial Sequencechemically synthesized 335atacgggagc caacaccaga cttattctcg cagatccata aaaggataca ccccagagca 60ggtgtgacgg at 7233672DNAArtificial Sequencechemically synthesized 336atccgtcaca cctgctctgg ggtgtatcct tttatggatc tgcgagaata agtctggtgt 60tggctcccgt at 7233772DNAArtificial Sequencechemically synthesized 337atacgggagc caacaccaca gaatcacgtg gagtacgaac aattgattca cccaagagca 60ggtgtgacgg at 7233872DNAArtificial Sequencechemically synthesized 338atccgtcaca cctgctcttg ggtgaatcaa ttgttcgtac tccacgtgat tctgtggtgt 60tggctcccgt at

7233972DNAArtificial Sequencechemically synthesized 339atacgggagc caacaccacg ggggcatctt ccattaaccc attacctcac cccaagagca 60ggtgtgacgg at 7234072DNAArtificial Sequencechemically synthesized 340atccgtcaca cctgctcttg gggtgaggta atgggttaat ggaagatgcc cccgtggtgt 60tggctcccgt at 7234172DNAArtificial Sequencechemically synthesized 341atacgggagc caacaccaga aaaaaacaaa cccaaggaat tacaccacaa aagtagagca 60ggtgtgacgg at 7234272DNAArtificial Sequencechemically synthesized 342atccgtcaca cctgctctac ttttgtggtg taattccttg ggtttgtttt tttctggtgt 60tggctcccgt at 7234371DNAArtificial Sequencechemically synthesized 343atacgggagc caacaccata agcagagaac tacaagacga tcccatattc caaagagcag 60gtgtgacgga t 7134471DNAArtificial Sequencechemically synthesized 344atccgtcaca cctgctcttt ggaatatggg atcgtcttgt agttctctgc ttatggtgtt 60ggctcccgta t 7134571DNAArtificial Sequencechemically synthesized 345atacgggagc caacaccagg ttggcgtcaa aagaaataag ggatatacat tagagagcag 60gtgtgacgga t 7134671DNAArtificial Sequencechemically synthesized 346atccgtcaca cctgctctct aatgtatatc ccttatttct tttgacgcca acctggtgtt 60ggctcccgta t 7134772DNAArtificial Sequencechemically synthesized 347atacgggagc caacaccacg gggtccccat cgtggccgac ataacaaaaa tcctagagca 60ggtgtgacgg at 7234872DNAArtificial Sequencechemically synthesized 348atccgtcaca cctgctctag gatttttgtt atgtcggcca cgatggggac cccgtggtgt 60tggctcccgt at 7234972DNAArtificial Sequencechemically synthesized 349atacgggagc caacaccatg aggctcacag taagagaagg accttggact cgtcagagca 60ggtgtgacgg at 7235072DNAArtificial Sequencechemically synthesized 350atccgtcaca cctgctctga cgagtccaag gtccttctct tactgtgagc ctcatggtgt 60tggctcccgt at 7235172DNAArtificial Sequencechemically synthesized 351atacgggagc caacaccagc acgccctact ttaccgccga gaatatgaga atagagagca 60ggtgtgacgg at 7235272DNAArtificial Sequencechemically synthesized 352atccgtcaca cctgctctct attctcatat tctcggcggt aaagtagggc gtgctggtgt 60tggctcccgt at 7235372DNAArtificial Sequencechemically synthesized 353atacgggagc caacaccacc gatgcgggcg ccttcggcgg accgcgaggc ctcgagagca 60ggtgtgacgg at 7235472DNAArtificial Sequencechemically synthesized 354atccgtcaca cctgctctcg aggcctcgcg gtccgccgaa ggcgcccgca tcggtggtgt 60tggctcccgt at 7235572DNAArtificial Sequencechemically synthesized 355atacgggagc caacaccagg cgtaacgtat tgagcagaat aaataagaca cgatagagca 60ggtgtgacgg at 7235672DNAArtificial Sequencechemically synthesized 356atccgtcaca cctgctctat cgtgtcttat ttattctgct caatacgtta cgcctggtgt 60tggctcccgt at 7235772DNAArtificial Sequencechemically synthesized 357atacgggagc caacaccagg cggacgccga ccgggcgggc ccggtcgagg ttttagagca 60ggtgtgacgg at 7235872DNAArtificial Sequencechemically synthesized 358atccgtcaca cctgctctaa aacctcgacc gggcccgccc ggtcggcgtc cgcctggtgt 60tggctcccgt at 7235972DNAArtificial Sequencechemically synthesized 359atacgggagc caacaccagg cgggctcgcg cgtctcccag agccgagtca tatgagagca 60ggtgtgacgg at 7236072DNAArtificial Sequencechemically synthesized 360atccgtcaca cctgctctca tatgactcgg ctctgggaga cgcgcgagcc cgcctggtgt 60tggctcccgt at 7236172DNAArtificial Sequencechemically synthesized 361atacgggagc caacaccacg taccaatccc ctcggattaa ctcgaacaac ggtaagagca 60ggtgtgacgg at 7236272DNAArtificial Sequencechemically synthesized 362atccgtcaca cctgctctta ccgttgttcg agttaatccg aggggattgg tacgtggtgt 60tggctcccgt at 7236372DNAArtificial Sequencechemically synthesized 363atacgggagc caacaccact ggtgaggcgc ctgcgccgac tggccgtccc cccgagagca 60ggtgtgacgg at 7236472DNAArtificial Sequencechemically synthesized 364atccgtcaca cctgctctcg gggggacggc cagtcggcgc aggcgcctca ccagtggtgt 60tggctcccgt at 7236571DNAArtificial Sequencechemically synthesized 365atacgggagc caacaccagc agggtggcgc gaccgaccta tttgttggct attagagcag 60gtgtgacgga t 7136671DNAArtificial Sequencechemically synthesized 366atccgtcaca cctgctctaa tagccaacaa ataggtcggt cgcgccaccc tgctggtgtt 60ggctcccgta t 7136772DNAArtificial Sequencechemically synthesized 367atacgggagc caacaccact aacaagaaga acgacacgta cagcagtact taccagagca 60ggtgtgacgg at 7236872DNAArtificial Sequencechemically synthesized 368atccgtcaca cctgctctgg taagtactgc tgtacgtgtc gttcttcttg ttagtggtgt 60tggctcccgt at 7236972DNAArtificial Sequencechemically synthesized 369atacgggagc caacaccacc acgctagcgc accaaaatct ataaaccgaa tcctagagca 60ggtgtgacgg at 7237072DNAArtificial Sequencechemically synthesized 370atccgtcaca cctgctctag gattcggttt atagattttg gtgcgctagc gtggtggtgt 60tggctcccgt at 7237162DNAArtificial Sequencechemically synthesized 371atacgggagc caacaccaga gcaggtgtga cggatagagc aggtagagca ggtgtgacgg 60at 6237262DNAArtificial Sequencechemically synthesized 372atccgtcaca cctgctctac ctgctctatc cgtcacacct gctctggtgt tggctcccgt 60at 6237372DNAArtificial Sequencechemically synthesized 373atacgggagc caacaccacg aacccccggt cccccggggg actatattcc tacgagagca 60ggtgtgacgg at 7237472DNAArtificial Sequencechemically synthesized 374atccgtcaca cctgctctcg taggaatata gtcccccggg ggaccggggg ttcgtggtgt 60tggctcccgt at 7237572DNAArtificial Sequencechemically synthesized 375atacgggagc caacaccaac ggagagcttc tccgcatgtg aaccgttacc ttccagagca 60ggtgtgacgg at 7237672DNAArtificial Sequencechemically synthesized 376atccgtcaca cctgctctgg aaggtaacgg ttcacatgcg gagaagctct ccgttggtgt 60tggctcccgt at 7237772DNAArtificial Sequencechemically synthesized 377atacgggagc caacaccaca tgacgggtga ctaaaagacg aaatctccca attaagagca 60ggtgtgacgg at 7237872DNAArtificial Sequencechemically synthesized 378atccgtcaca cctgctctta attgggagat ttcgtctttt agtcacccgt catgtggtgt 60tggctcccgt at 7237972DNAArtificial Sequencechemically synthesized 379atacgggagc caacaccacc tgagcgccgg cagcactcac tatttgtccc cgcaagagca 60ggtgtgacgg at 7238072DNAArtificial Sequencechemically synthesized 380atccgtcaca cctgctcttg cggggacaaa tagtgagtgc tgccggcgct caggtggtgt 60tggctcccgt at 7238172DNAArtificial Sequencechemically synthesized 381atacgggagc caacaccaac atcctctgct gccggccgga ttcggccgag tgccagagca 60ggtgtgacgg at 7238272DNAArtificial Sequencechemically synthesized 382atccgtcaca cctgctctgg cactcggccg aatccggccg gcagcagagg atgttggtgt 60tggctcccgt at 7238372DNAArtificial Sequencechemically synthesized 383atacgggagc caacaccacg ccgccccagc gtcatcggaa gtctaatcag atccagagca 60ggtgtgacgg at 7238472DNAArtificial Sequencechemically synthesized 384atccgtcaca cctgctctgg atctgattag acttccgatg acgctggggc ggcgtggtgt 60tggctcccgt at 7238572DNAArtificial Sequencechemically synthesized 385atacgggagc caacaccagg gtggcgccgg ccagcgactc ctgccttcca agctagagca 60ggtgtgacgg at 7238672DNAArtificial Sequencechemically synthesized 386atccgtcaca cctgctctag cttggaaggc aggagtcgct ggccggcgcc accctggtgt 60tggctcccgt at 7238772DNAArtificial Sequencechemically synthesized 387atacgggagc caacaccaga cgggttggat cacgcctaat tgggcccatg ttttagagca 60ggtgtgacgg at 7238872DNAArtificial Sequencechemically synthesized 388atccgtcaca cctgctctaa aacatgggcc caattaggcg tgatccaacc cgtctggtgt 60tggctcccgt at 7238972DNAArtificial Sequencechemically synthesized 389atacgggagc caacaccact ctcaagtcga agatagacga aaagatttcg ccccagagca 60ggtgtgacgg at 7239072DNAArtificial Sequencechemically synthesized 390atccgtcaca cctgctctgg ggcgaaatct tttcgtctat cttcgacttg agagtggtgt 60tggctcccgt at 7239172DNAArtificial Sequencechemically synthesized 391atacgggagc caacaccatg cgagcatcat tacttcctac catggatccg gactagagca 60ggtgtgacgg at 7239272DNAArtificial Sequencechemically synthesized 392atccgtcaca cctgctctag tccggatcca tggtaggaag taatgatgct cgcatggtgt 60tggctcccgt at 7239372DNAArtificial Sequencechemically synthesized 393atacgggagc caacaccatc ggcgaccgtt agccttccgg ctacaatcag ggccagagca 60ggtgtgacgg at 7239472DNAArtificial Sequencechemically synthesized 394atccgtcaca cctgctctgg ccctgattgt agccggaagg ctaacggtcg ccgatggtgt 60tggctcccgt at 7239570DNAArtificial Sequencechemically synthesized 395atacgggagc caacaccaga gcgggtgtga cggatatacg ggagccaaca ccagagcagg 60tgtgacggat 7039670DNAArtificial Sequencechemically synthesized 396atccgtcaca cctgctctgg tgttggctcc cgtatatccg tcacacccgc tctggtgttg 60gctcccgtat 7039770DNAArtificial Sequencechemically synthesized 397atacgggagc caacaccacc gaattgattg ataaaaaggg ttagatcgct ccagagcagg 60tgtgacggat 7039870DNAArtificial Sequencechemically synthesized 398atccgtcaca cctgctctgg agcgatctaa ccctttttat caatcaattc ggtggtgttg 60gctcccgtat 7039972DNAArtificial Sequencechemically synthesized 399atacgggagc caacaccagc agggagcaat aaaaaccatt aaaagtcagc tgacagagca 60ggtgtgacgg at 7240072DNAArtificial Sequencechemically synthesized 400atccgtcaca cctgctctgt cagctgactt ttaatggttt ttattgctcc ctgctggtgt 60tggctcccgt at 7240172DNAArtificial Sequencechemically synthesized 401atacgggagc caacaccaca ggctcacgac cccggcttgg gccgggccct ccccagagca 60ggtgtgacgg at 7240272DNAArtificial Sequencechemically synthesized 402atccgtcaca cctgctctgg ggagggcccg gcccaagccg gggtcgtgag cctgtggtgt 60tggctcccgt at 7240372DNAArtificial Sequencechemically synthesized 403atacgggagc caacaccatc ccaagtcaat acctccgaaa taagttgaat taccagagca 60ggtgtgacgg at 7240472DNAArtificial Sequencechemically synthesized 404atccgtcaca cctgctctgg taattcaact tatttcggag gtattgactt gggatggtgt 60tggctcccgt at 7240572DNAArtificial Sequencechemically synthesized 405atacgggagc caacaccagt atctggatca agagaactga aggatatttc taacagagca 60ggtgtgacgg at 7240672DNAArtificial Sequencechemically synthesized 406atccgtcaca cctgctctgt tagaaatatc cttcagttct cttgatccag atactggtgt 60tggctcccgt at 7240772DNAArtificial Sequencechemically synthesized 407atacgggagc caacaccacg tgctgactat actattcaaa aacaacaccc taggagagca 60ggtgtgacgg at 7240872DNAArtificial Sequencechemically synthesized 408atccgtcaca cctgctctcc tagggtgttg tttttgaata gtatagtcag cacgtggtgt 60tggctcccgt at 7240972DNAArtificial Sequencechemically synthesized 409atacgggagc caacaccacg gataagaatc aataggcaat gaaagaagac cggcagagca 60ggtgtgacgg at 7241072DNAArtificial Sequencechemically synthesized 410atccgtcaca cctgctctgc cggtcttctt tcattgccta ttgattctta tccgtggtgt 60tggctcccgt at 7241172DNAArtificial Sequencechemically synthesized 411atacgggagc caacaccacg cgaagcgaga tccgccgtat tagcaatttg tgtgagagca 60ggtgtgacgg at 7241272DNAArtificial Sequencechemically synthesized 412atccgtcaca cctgctctca cacaaattgc taatacggcg gatctcgctt cgcgtggtgt 60tggctcccgt at 7241372DNAArtificial Sequencechemically synthesized 413atacgggagc caacaccacc gaccatggag cggacccatt agatcttcaa tcctagagca 60ggtgtgacgg at 7241472DNAArtificial Sequencechemically synthesized 414atccgtcaca cctgctctag gattgaagat ctaatgggtc cgctccatgg tcggtggtgt 60tggctcccgt at 7241572DNAArtificial Sequencechemically synthesized 415atacgggagc caacaccacc ccgaccagga gccggggctc ccgcccgcct ccccagagca 60ggtgtgacgg at 7241672DNAArtificial Sequencechemically synthesized 416atccgtcaca cctgctctgg ggaggcgggc gggagccccg gctcctggtc ggggtggtgt 60tggctcccgt at 7241772DNAArtificial Sequencechemically synthesized 417atacgggagc caacaccagg cgagcggtcc acggccggcc ggaccgtcaa tggtagagca 60ggtgtgacgg at 7241872DNAArtificial Sequencechemically synthesized 418atccgtcaca cctgctctac cattgacggt ccggccggcc gtggaccgct cgcctggtgt 60tggctcccgt at 7241972DNAArtificial Sequencechemically synthesized 419atacgggagc caacaccagg aggcggacga tctccctccc ggccaaaggc gcgtagagca 60ggtgtgacgg at 7242072DNAArtificial Sequencechemically synthesized 420atccgtcaca cctgctctac gcgcctttgg ccgggaggga gatcgtccgc ctcctggtgt 60tggctcccgt at 7242172DNAArtificial Sequencechemically synthesized 421atacgggagc caacaccacg gataagaatc aataggcaat gaaagaagac cggcagagca 60ggtgtgacgg at 7242272DNAArtificial Sequencechemically synthesized 422atccgtcaca cctgctctgc cggtcttctt tcattgccta ttgattctta tccgtggtgt 60tggctcccgt

at 7242372DNAArtificial Sequencechemically synthesized 423atacgggagc caacaccact gtttaataaa tgcacctgaa aaaaacgtgt gtcaagagca 60ggtgtgacgg at 7242472DNAArtificial Sequencechemically synthesized 424atccgtcaca cctgctcttg acacacgttt ttttcaggtg catttattaa acagtggtgt 60tggctcccgt at 7242571DNAArtificial Sequencechemically synthesized 425atacgggagc caacaccaag cgtctagcgg gactaagctg aaacatacca gctagagcag 60gtgtgacgga t 7142671DNAArtificial Sequencechemically synthesized 426atccgtcaca cctgctctag ctggtatgtt tcagcttagt cccgctagac gcttggtgtt 60ggctcccgta t 7142772DNAArtificial Sequencechemically synthesized 427atacgggagc caacaccagg cgaccgacac gattataacc ttgtaaaggc cgtaagagca 60ggtgtgacgg at 7242872DNAArtificial Sequencechemically synthesized 428atccgtcaca cctgctctta cggcctttac aaggttataa tcgtgtcggt cgcctggtgt 60tggctcccgt at 7242972DNAArtificial Sequencechemically synthesized 429atacgggagc caacaccagt acggcggtgt ccgaactcac tatacccagt tgaaagagca 60ggtgtgacgg at 7243072DNAArtificial Sequencechemically synthesized 430atccgtcaca cctgctcttt caactgggta tagtgagttc ggacaccgcc gtactggtgt 60tggctcccgt at 7243172DNAArtificial Sequencechemically synthesized 431atacgggagc caacaccaga cctgacaacg aaaaccccag ttgtcgccat agccagagca 60ggtgtgacgg at 7243272DNAArtificial Sequencechemically synthesized 432atccgtcaca cctgctctgg ctatggcgac aactggggtt ttcgttgtca ggtctggtgt 60tggctcccgt at 7243369DNAArtificial Sequencechemically synthesized 433atacgggagc caacaccata gtgttgggcc aatacggtaa cgtgtccttg gagagcaggt 60gtgacggat 6943469DNAArtificial Sequencechemically synthesized 434atccgtcaca cctgctctcc aaggacacgt taccgtattg gcccaacact atggtgttgg 60ctcccgtat 6943572DNAArtificial Sequencechemically synthesized 435atacgggagc caacaccata agcgcaacac agtccatccc tgagtgagat agcgagagca 60ggtgtgacgg at 7243672DNAArtificial Sequencechemically synthesized 436atccgtcaca cctgctctcg ctatctcact cagggatgga ctgtgttgcg cttatggtgt 60tggctcccgt at 7243758DNAArtificial Sequencechemically synthesized 437atacgggagc caacaccacg cacatactag ctatctcatc agagcaggtg tgacggat 5843858DNAArtificial Sequencechemically synthesized 438atccgtcaca cctgctctga tgagatagct agtatgtgcg tggtgttggc tcccgtat 5843958DNAArtificial Sequencechemically synthesized 439atacgggagc caacaccact aacttgttgc tgatcttacc agagcaggtg tgacggat 5844058DNAArtificial Sequencechemically synthesized 440atccgtcaca cctgctctgg taagatcagc aacaagttag tggtgttggc tcccgtat 5844172DNAArtificial Sequencechemically synthesized 441atacgggagc caacaccacc cgtttttgat ctaatgagga tacaatattc gtcnagagca 60ggtgtgacgg at 7244272DNAArtificial Sequencechemically synthesized 442atccgtcaca cctgctctng acgaatattg tatcctcatt agatcaaaaa cgggtggtgt 60tggctcccgt at 7244372DNAArtificial Sequencechemically synthesized 443atacgggagc caacaccagt tgtgggaaca tcaggctaag tatgagacgg aacgagagca 60ggtgtgacgg at 7244472DNAArtificial Sequencechemically synthesized 444atccgtcaca cctgctctcg ttccgtctca tacttagcct gatgttccca caactggtgt 60tggctcccgt at 7244572DNAArtificial Sequencechemically synthesized 445atacgggagc caacaccata gacaatggcg tacttttcgt aattccacaa gaatagagca 60ggtgtgacgg at 7244672DNAArtificial Sequencechemically synthesized 446atccgtcaca cctgctctat tcttgtggaa ttacgaaaag tacgccattg tctatggtgt 60tggctcccgt at 7244769DNAArtificial Sequencechemically synthesized 447atacgggagc caacaccata gtgttgggcc aatacggtaa cgtgtccttg gagagcaggt 60gtgacggat 6944869DNAArtificial Sequencechemically synthesized 448atccgtcaca cctgctctcc aaggacacgt taccgtattg gcccaacact atggtgttgg 60ctcccgtat 6944958DNAArtificial Sequencechemically synthesized 449atacgggagc caacaccacc acaaaagcat tcgcccttac agagcaggtg tgacggat 5845058DNAArtificial Sequencechemically synthesized 450atccgtcaca cctgctctgt aagggcgaat gcttttgtgg tggtgttggc tcccgtat 5845172DNAArtificial Sequencechemically synthesized 451atacgggagc caacaccagc gtgtagctag tttcaggatt gtagtatgta atatagagca 60ggtgtgacgg at 7245272DNAArtificial Sequencechemically synthesized 452atccgtcaca cctgctctat attacatact acaatcctga aactagctac acgctggtgt 60tggctcccgt at 7245358DNAArtificial Sequencechemically synthesized 453atacgggagc caacaccacg cacatactag ctatctcatc agagcaggtg tgacggat 5845458DNAArtificial Sequencechemically synthesized 454atccgtcaca cctgctctga tgagatagct agtatgtgcg tggtgttggc tcccgtat 5845572DNAArtificial Sequencechemically synthesized 455atacgggagc caacaccatc agagatcatc taacgaaaat catgggtctc gcccagagca 60ggtgtgacgg at 7245672DNAArtificial Sequencechemically synthesized 456atccgtcaca cctgctctgg gcgagaccca tgattttcgt tagatgatct ctgatggtgt 60tggctcccgt at 7245772DNAArtificial Sequencechemically synthesized 457atacgggagc caacaccagc aaagaatagt gagccctatg atcatctgtt cgtcagagca 60ggtgtgacgg at 7245872DNAArtificial Sequencechemically synthesized 458atccgtcaca cctgctctga cgaacagatg atcatagggc tcactattct ttgctggtgt 60tggctcccgt at 7245972DNAArtificial Sequencechemically synthesized 459atacgggagc caacaccaga catcatgtcg catatctgga tctagaggct attcagagca 60ggtgtgacgg at 7246072DNAArtificial Sequencechemically synthesized 460atccgtcaca cctgctctga atagcctcta gatccagata tgcgacatga tgtctggtgt 60tggctcccgt at 7246169DNAArtificial Sequencechemically synthesized 461atacgggagc caacaccata gtgttgggcc aatacggtaa cgtgtacttg gagagcaggt 60gtgacggat 6946269DNAArtificial Sequencechemically synthesized 462atccgtcaca cctgctctcc aagtacacgt taccgtattg gcccaacact atggtgttgg 60ctcccgtat 6946372DNAArtificial Sequencechemically synthesized 463atacgggagc caacaccaga gagttcatgt tgcacccggg tcgtcgcgtt atgcagagca 60ggtgtgacgg at 7246472DNAArtificial Sequencechemically synthesized 464atccgtcaca cctgctctgc ataacgcgac gacccgggtg caacatgaac tctctggtgt 60tggctcccgt at 7246572DNAArtificial Sequencechemically synthesized 465atacgggagc caacaccatc tatctgaggc ctatttagca cctgttgtca ccctagagca 60ggtgtgacgg at 7246672DNAArtificial Sequencechemically synthesized 466atccgtcaca cctgctctag ggtgacaaca ggtgctaaat aggcctcaga tagatggtgt 60tggctcccgt at 7246772DNAArtificial Sequencechemically synthesized 467atacgggagc caacaccatt ctatcgttcc ggacgcttat gccttgccat ctacagagca 60ggtgtgacgg at 7246872DNAArtificial Sequencechemically synthesized 468atccgtcaca cctgctctgt agatggcaag gcataagcgt ccggaacgat agaatggtgt 60tggctcccgt at 7246972DNAArtificial Sequencechemically synthesized 469atacgggagc caacaccaca tttcgcacac ccgagcccta gagggctagg gaccagagca 60ggtgtgacgg at 7247072DNAArtificial Sequencechemically synthesized 470atccgtcaca cctgctctgg tccctagccc tctagggctc gggtgtgcga aatgtggtgt 60tggctcccgt at 7247172DNAArtificial Sequencechemically synthesized 471atacgggagc caacaccact ggcacgaaca atcatgaaat agggcatccg agagagagca 60ggtgtgacgg at 7247272DNAArtificial Sequencechemically synthesized 472atccgtcaca cctgctctct ctcggatgcc ctatttcatg attgttcgtg ccagtggtgt 60tggctcccgt at 7247372DNAArtificial Sequencechemically synthesized 473atacgggagc caacaccatg tgtcatggtg ggcgtggcta tccgagcaag ctctagagca 60ggtgtgacgg at 7247472DNAArtificial Sequencechemically synthesized 474atccgtcaca cctgctctag agcttgctcg gatagccacg cccaccatga cacatggtgt 60tggctcccgt at 7247572DNAArtificial Sequencechemically synthesized 475atacgggagc caacaccaca tgcaaataca catcatgatg acggatccta ttgtagagca 60ggtgtgacgg at 7247672DNAArtificial Sequencechemically synthesized 476atccgtcaca cctgctctac aataggatcc gtcatcatga tgtgtatttg catgtggtgt 60tggctcccgt at 7247772DNAArtificial Sequencechemically synthesized 477atacgggagc caacaccagt agagcaagct attacgcgaa gctagaatga gatcagagca 60ggtgtgacgg at 7247872DNAArtificial Sequencechemically synthesized 478atccgtcaca cctgctctga tctcattcta gcttcgcgta atagcttgct ctactggtgt 60tggctcccgt at 7247972DNAArtificial Sequencechemically synthesized 479atacgggagc caacaccacc cattggggat gcattagatg cagttgatta tgcgagagca 60ggtgtgacgg at 7248072DNAArtificial Sequencechemically synthesized 480atccgtcaca cctgctctcg cataatcaac tgcatctaat gcatccccaa tgggtggtgt 60tggctcccgt at 7248172DNAArtificial Sequencechemically synthesized 481atacgggagc caacaccata caaccgtcca agcgttactc tttacatact ctccagagca 60ggtgtgacgg at 7248272DNAArtificial Sequencechemically synthesized 482atccgtcaca cctgctctgg agagtatgta aagagtaacg cttggacggt tgtatggtgt 60tggctcccgt at 7248372DNAArtificial Sequencechemically synthesized 483atacgggagc caacaccaat tttgactgtt ccaggctcag tattggtatt caggagagca 60ggtgtgacgg at 7248472DNAArtificial Sequencechemically synthesized 484atccgtcaca cctgctctcc tgaataccaa tactgagcct ggaacagtca aaattggtgt 60tggctcccgt at 7248572DNAArtificial Sequencechemically synthesized 485atacgggagc caacaccacg aaatgatgta tctagttcct cgtgtcctga ttcgagagca 60ggtgtgacgg at 7248672DNAArtificial Sequencechemically synthesized 486atccgtcaca cctgctctcg aatcaggaca cgaggaacta gatacatcat ttcgtggtgt 60tggctcccgt at 7248772DNAArtificial Sequencechemically synthesized 487atacgggagc caacaccacc gctgcccagg tataacaccg cggtacgatc tcatagagca 60ggtgtgacgg at 7248872DNAArtificial Sequencechemically synthesized 488atccgtcaca cctgctctat gagatcgtac cgcggtgtta tacctgggca gcggtggtgt 60tggctcccgt at 7248972DNAArtificial Sequencechemically synthesized 489atacgggagc caacaccaaa gggatctgga aaaccccgta ttgatctaag gcgcagagca 60ggtgtgacgg at 7249072DNAArtificial Sequencechemically synthesized 490atccgtcaca cctgctctgc gccttagatc aatacggggt tttccagatc cctttggtgt 60tggctcccgt at 7249172DNAArtificial Sequencechemically synthesized 491atacgggagc caacaccata cccccctctt taggccatca cgttctgtcg atttagagca 60ggtgtgacgg at 7249272DNAArtificial Sequencechemically synthesized 492atccgtcaca cctgctctaa atcgacagaa cgtgatggcc taaagagggg ggtatggtgt 60tggctcccgt at 7249372DNAArtificial Sequencechemically synthesized 493atacgggagc caacaccata cccccctctt taggccatca cgttctctcg atttagagca 60ggtgtgacgg at 7249472DNAArtificial Sequencechemically synthesized 494atccgtcaca cctgctctaa atcgagagaa cgtgatggcc taaagagggg ggtatggtgt 60tggctcccgt at 7249572DNAArtificial Sequencechemically synthesized 495atacgggagc caacaccatc atggtcgcga atcaaccgta tctcagctgc cttgagagca 60ggtgtgacgg at 7249672DNAArtificial Sequencechemically synthesized 496atccgtcaca cctgctctca aggcagctga gatacggttg attcgcgacc atgatggtgt 60tggctcccgt at 7249772DNAArtificial Sequencechemically synthesized 497atacgggagc caacaccacc cgtttttgat ctaatgagga tacaatattc gtctagagca 60ggtgtgacgg at 7249872DNAArtificial Sequencechemically synthesized 498atccgtcaca cctgctctag acgaatattg tatcctcatt agatcaaaaa cgggtggtgt 60tggctcccgt at 7249972DNAArtificial Sequencechemically synthesized 499atacgggagc caacaccata taaaaggcga acggtcactt tggtcggagt acgtagagca 60ggtgtgacgg at 7250072DNAArtificial Sequencechemically synthesized 500atccgtcaca cctgctctac gtactccgac caaagtgacc gttcgccttt tatatggtgt 60tggctcccgt at 7250157DNAArtificial Sequencechemically synthesized 501atacgggagc caacaccagt gttggcgtct tccctgatca gagcaggtgt gacggat 5750257DNAArtificial Sequencechemically synthesized 502atccgtcaca cctgctctga tcagggaaga cgccaacact ggtgttggct cccgtat 5750372DNAArtificial Sequencechemically synthesized 503atacgggagc caacaccaga ggtgagaagc ccattacacc gagcggacct gcagagagca 60ggtgtgacgg at 7250472DNAArtificial Sequencechemically synthesized 504atccgtcaca cctgctctct gcaggtccgc tcggtgtaat gggcttctca cctctggtgt 60tggctcccgt at 7250572DNAArtificial Sequencechemically synthesized 505atacgggagc caacaccaga cgaaatcaaa tctaaaagtg ataagccaga agtcagagca 60ggtgtgacgg at 7250672DNAArtificial Sequencechemically synthesized 506atccgtcaca cctgctctga cttctggctt atcactttta gatttgattt cgtctggtgt 60tggctcccgt at 7250772DNAArtificial Sequencechemically synthesized 507atacgggagc caacaccacc cgtttttgat ctaatgagga tacaatattc gtctagagca 60ggtgtgacgg at 7250872DNAArtificial Sequencechemically synthesized 508atccgtcaca cctgctctag acgaatattg tatcctcatt agatcaaaaa cgggtggtgt 60tggctcccgt at 7250972DNAArtificial Sequencechemically synthesized 509atacgggagc caacaccaac acgcagaaga gatgcattgt atgatcggtg tacgagagca 60ggtgtgacgg

at 7251072DNAArtificial Sequencechemically synthesized 510atccgtcaca cctgctctcg tacaccgatc atacaatgca tctcttctgc gtgttggtgt 60tggctcccgt at 7251172DNAArtificial Sequencechemically synthesized 511atacgggagc caacaccacg ccaacagtgt tttagagtca tgcacaaaag tatcagagca 60ggtgtgacgg at 7251272DNAArtificial Sequencechemically synthesized 512atccgtcaca cctgctctga tacttttgtg catgactcta aaacactgtt ggcgtggtgt 60tggctcccgt at 7251372DNAArtificial Sequencechemically synthesized 513atacgggagc caacaccagg gtggtttacg atcggcaggt cgtgcgtgcg acacagagca 60ggtgtgacgg at 7251472DNAArtificial Sequencechemically synthesized 514atccgtcaca cctgctctgt gtcgcacgca cgacctgccg atcgtaaacc accctggtgt 60tggctcccgt at 7251572DNAArtificial Sequencechemically synthesized 515atacgggagc caacaccaac ggcgacgggc gagtacacag gtgtaagtcg gggtagagca 60ggtgtgacgg at 7251672DNAArtificial Sequencechemically synthesized 516atccgtcaca cctgctctac cccgacttac acctgtgtac tcgcccgtcg ccgttggtgt 60tggctcccgt at 7251772DNAArtificial Sequencechemically synthesized 517atacgggagc caacaccaag caatagaaca ccctttgtcg cactggatgc gatgagagca 60ggtgtgacgg at 7251872DNAArtificial Sequencechemically synthesized 518atccgtcaca cctgctctca tcgcatccag tgcgacaaag ggtgttctat tgcttggtgt 60tggctcccgt at 7251972DNAArtificial Sequencechemically synthesized 519atacgggagc caacaccaca aagtgttgta agggcaaaac aaatatgtac ctcgagagca 60ggtgtgacgg at 7252072DNAArtificial Sequencechemically synthesized 520atccgtcaca cctgctctcg aggtacatat ttgttttgcc cttacaacac tttgtggtgt 60tggctcccgt at 7252172DNAArtificial Sequencechemically synthesized 521atacgggagc caacaccaag ccaaagaccc ttatcaaacg gccatgcccg gggcagagca 60ggtgtgacgg at 7252272DNAArtificial Sequencechemically synthesized 522atccgtcaca cctgctctgc cccgggcatg gccgtttgat aagggtcttt ggcttggtgt 60tggctcccgt at 7252372DNAArtificial Sequencechemically synthesized 523atacgggagc caacaccaca ttaaccccaa aggatacatg tttgtcccat cgcaagagca 60ggtgtgacgg at 7252472DNAArtificial Sequencechemically synthesized 524atccgtcaca cctgctcttg cgatgggaca aacatgtatc ctttggggtt aatgtggtgt 60tggctcccgt at 7252572DNAArtificial Sequencechemically synthesized 525atacgggagc caacaccata tcacggaccc cccaggttgc cgaattactc ttacagagca 60ggtgtgacgg at 7252672DNAArtificial Sequencechemically synthesized 526atccgtcaca cctgctctgt aagagtaatt cggcaacctg gggggtccgt gatatggtgt 60tggctcccgt at 7252770DNAArtificial Sequencechemically synthesized 527atacgggagc caacaccatt cccgcatcgc gcgttttcag cctttgaccg ttagagcagg 60tgtgacggat 7052870DNAArtificial Sequencechemically synthesized 528atccgtcaca cctgctctaa cggtcaaagg ctgaaaacgc gcgatgcggg aatggtgttg 60gctcccgtat 7052972DNAArtificial Sequencechemically synthesized 529atacgggagc caacaccaac gtgtgctgtg ttactgccct tctctgtagc cgtgagagca 60ggtgtgacgg at 7253072DNAArtificial Sequencechemically synthesized 530atccgtcaca cctgctctca cggctacaga gaagggcagt aacacagcac acgttggtgt 60tggctcccgt at 7253172DNAArtificial Sequencechemically synthesized 531atacgggagc caacaccacc ttttaaaacg ctagccagct tagtccattc caccagagca 60ggtgtgacgg at 7253272DNAArtificial Sequencechemically synthesized 532atccgtcaca cctgctctgg tggaatggac taagctggct agcgttttaa aaggtggtgt 60tggctcccgt at 7253372DNAArtificial Sequencechemically synthesized 533atacgggagc caacaccaat ctaacagatt gcagctcgcc tgtcccggcg tactagagca 60ggtgtgacgg at 7253472DNAArtificial Sequencechemically synthesized 534atccgtcaca cctgctctag tacgccggga caggcgagct gcaatctgtt agattggtgt 60tggctcccgt at 7253572DNAArtificial Sequencechemically synthesized 535atacgggagc caacaccacc tattacagac ccaatttcca cctggcattt ctatagagca 60ggtgtgacgg at 7253672DNAArtificial Sequencechemically synthesized 536atccgtcaca cctgctctat agaaatgcca ggtggaaatt gggtctgtaa taggtggtgt 60tggctcccgt at 7253772DNAArtificial Sequencechemically synthesized 537atacgggagc caacaccaca tatcctacac tcccataccc cactgtagac acgcagagca 60ggtgtgacgg at 7253872DNAArtificial Sequencechemically synthesized 538atccgtcaca cctgctctgc gtgtctacag tggggtatgg gagtgtagga tatgtggtgt 60tggctcccgt at 7253972DNAArtificial Sequencechemically synthesized 539atacgggagc caacaccaaa ccgagtgctg gtggccctct ctgccatata agtgagagca 60ggtgtgacgg at 7254072DNAArtificial Sequencechemically synthesized 540atccgtcaca cctgctctca cttatatggc agagagggcc accagcactc ggtttggtgt 60tggctcccgt at 7254173DNAArtificial Sequencechemically synthesized 541atacgggagc caacaccacc ttttaaaacg ctagctagct tagtccaatt ccaccagagc 60aggtgtgacg gat 7354273DNAArtificial Sequencechemically synthesized 542atccgtcaca cctgctctgg tggaattgga ctaagctagc tagcgtttta aaaggtggtg 60ttggctcccg tat 7354372DNAArtificial Sequencechemically synthesized 543atacgggagc caacaccatg acattgcaac tatacgctta cccacgtcag ctccagagca 60ggtgtgacgg at 7254472DNAArtificial Sequencechemically synthesized 544atccgtcaca cctgctctgg agctgacgtg ggtaagcgta tagttgcaat gtcatggtgt 60tggctcccgt at 7254572DNAArtificial Sequencechemically synthesized 545atacgggagc caacaccatt aacctgaaag taccagtgtc agtttaccct acctagagca 60ggtgtgacgg at 7254672DNAArtificial Sequencechemically synthesized 546atccgtcaca cctgctctag gtagggtaaa ctgacactgg tactttcagg ttaatggtgt 60tggctcccgt at 7254772DNAArtificial Sequencechemically synthesized 547atacgggagc caacaccagg cattagtgta aagcactaag agtcaggctg tagcagagca 60ggtgtgacgg at 7254872DNAArtificial Sequencechemically synthesized 548atccgtcaca cctgctctgc tacagcctga ctcttagtgc tttacactaa tgcctggtgt 60tggctcccgt at 7254972DNAArtificial Sequencechemically synthesized 549atacgggagc caacaccatg acacgccgat tatggacgtt gcgaactagt tggtagagca 60ggtgtgacgg at 7255072DNAArtificial Sequencechemically synthesized 550atccgtcaca cctgctctac caactagttc gcaacgtcca taatcggcgt gtcatggtgt 60tggctcccgt at 7255172DNAArtificial Sequencechemically synthesized 551atacgggagc caacaccact caatcccacc cttatttaga gcggttacat cacaagagca 60ggtgtgacgg at 7255272DNAArtificial Sequencechemically synthesized 552atccgtcaca cctgctcttg tgatgtaacc gctctaaata agggtgggat tgagtggtgt 60tggctcccgt at 7255372DNAArtificial Sequencechemically synthesized 553atacgggagc caacaccaat ttgtgaaaat attcccgtgt tttccttgag cagcagagca 60ggtgtgacgg at 7255472DNAArtificial Sequencechemically synthesized 554atccgtcaca cctgctctgc tgctcaagga aaacacggga atattttcac aaattggtgt 60tggctcccgt at 7255572DNAArtificial Sequencechemically synthesized 555atacgggagc caacaccagc gtaaaacctt gtaccaattg atgacactag cggtagagca 60ggtgtgacgg at 7255672DNAArtificial Sequencechemically synthesized 556atccgtcaca cctgctctac cgctagtgtc atcaattggt acaaggtttt acgctggtgt 60tggctcccgt at 7255772DNAArtificial Sequencechemically synthesized 557atacgggagc caacaccaca gctcaccgcg cttgccgtgc cttacgtctg tccaagagca 60ggtgtgacgg at 7255872DNAArtificial Sequencechemically synthesized 558atccgtcaca cctgctcttg gacagacgta aggcacggca agcgcggtga gctgtggtgt 60tggctcccgt at 7255971DNAArtificial Sequencechemically synthesized 559atacgggagc caacaccatc accgtactgg agccatcgtt catccagcaa tctagagcag 60gtgtgacgga t 7156071DNAArtificial Sequencechemically synthesized 560atccgtcaca cctgctctag attgctggat gaacgatggc tccagtacgg tgatggtgtt 60ggctcccgta t 7156172DNAArtificial Sequencechemically synthesized 561atacgggagc caacaccacc tctcacatta tattgtgaat acttcgtgct gtttagagca 60ggtgtgacgg at 7256272DNAArtificial Sequencechemically synthesized 562atccgtcaca cctgctctaa acagcacgaa gtattcacaa tataatgtga gaggtggtgt 60tggctcccgt at 7256372DNAArtificial Sequencechemically synthesized 563atacgggagc caacaccagt gcttctgcct tccttatgtt ctatctgatt atctagagca 60ggtgtgacgg at 7256472DNAArtificial Sequencechemically synthesized 564atccgtcaca cctgctctag ataatcagat agaacataag gaaggcagaa gcactggtgt 60tggctcccgt at 7256572DNAArtificial Sequencechemically synthesized 565atacgggagc caacaccaaa attaacgtgt tgagatatgt ggaacctcta ctaaagagca 60ggtgtgacgg at 7256672DNAArtificial Sequencechemically synthesized 566atccgtcaca cctgctcttt agtagaggtt ccacatatct caacacgtta attttggtgt 60tggctcccgt at 7256772DNAArtificial Sequencechemically synthesized 567atacgggagc caacaccagt ccccattccc gtctgaatga ctgtccataa caggagagca 60ggtgtgacgg at 7256872DNAArtificial Sequencechemically synthesized 568atccgtcaca cctgctctcc tgttatggac agtcattcag acgggaatgg ggactggtgt 60tggctcccgt at 7256972DNAArtificial Sequencechemically synthesized 569atacgggagc caacaccacc tgaatactaa cactaagacc cgacttgtgt tcacagagca 60ggtgtgacgg at 7257072DNAArtificial Sequencechemically synthesized 570atccgtcaca cctgctctgt gaacacaagt cgggtcttag tgttagtatt caggtggtgt 60tggctcccgt at 7257172DNAArtificial Sequencechemically synthesized 571atacgggagc caacaccagc taggatgtca ccaccggtca cttcatgtcg agacagagca 60ggtgtgacgg at 7257272DNAArtificial Sequencechemically synthesized 572atccgtcaca cctgctctgt ctcgacatga agtgaccggt ggtgacatcc tagctggtgt 60tggctcccgt at 7257372DNAArtificial Sequencechemically synthesized 573atacgggagc caacaccata actattggcc tcgagccgct ccagtcatca tcctagagca 60ggtgtgacgg at 7257472DNAArtificial Sequencechemically synthesized 574atccgtcaca cctgctctag gatgatgact ggagcggctc gaggccaata gttatggtgt 60tggctcccgt at 7257572DNAArtificial Sequencechemically synthesized 575atacgggagc caacaccaga gcttgctttt cttacgtcgt tgccgggagc cggaagagca 60ggtgtgacgg at 7257672DNAArtificial Sequencechemically synthesized 576atccgtcaca cctgctcttc cggctcccgg caacgacgta agaaaagcaa gctctggtgt 60tggctcccgt at 7257772DNAArtificial Sequencechemically synthesized 577atacgggagc caacaccacc ggggacacta tacattctct agacaatata gtttagagca 60ggtgtgacgg at 7257872DNAArtificial Sequencechemically synthesized 578atccgtcaca cctgctctaa actatattgt ctagagaatg tatagtgtcc ccggtggtgt 60tggctcccgt at 7257972DNAArtificial Sequencechemically synthesized 579atacgggagc caacaccaga tagttgtcct gcatatgttg tcgtgtgcta atgtagagca 60ggtgtgacgg at 7258072DNAArtificial Sequencechemically synthesized 580atccgtcaca cctgctctac attagcacac gacaacatat gcaggacaac tatctggtgt 60tggctcccgt at 7258172DNAArtificial Sequencechemically synthesized 581atacgggagc caacaccaac tctacagcct aatctgcact ttacaggata cgtcagagca 60ggtgtgacgg at 7258272DNAArtificial Sequencechemically synthesized 582atccgtcaca cctgctctga cgtatcctgt aaagtgcaga ttaggctgta gagttggtgt 60tggctcccgt at 7258372DNAArtificial Sequencechemically synthesized 583atacgggagc caacaccacg cacgtggtct acacggccac ctattctcat ttgtagagca 60ggtgtgacgg at 7258472DNAArtificial Sequencechemically synthesized 584atccgtcaca cctgctctac aaatgagaat aggtggccgt gtagaccacg tgcgtggtgt 60tggctcccgt at 7258572DNAArtificial Sequencechemically synthesized 585atacgggagc caacaccatc ctctgttctt cacgcgggag cactttctat ctttagagca 60ggtgtgacgg at 7258672DNAArtificial Sequencechemically synthesized 586atccgtcaca cctgctctaa agatagaaag tgctcccgcg tgaagaacag aggatggtgt 60tggctcccgt at 7258772DNAArtificial Sequencechemically synthesized 587atacgggagc caacaccatc aatggcaagt tgttccatat tgaccatggt tcacagagca 60ggtgtgacgg at 7258872DNAArtificial Sequencechemically synthesized 588atccgtcaca cctgctctgt gaaccatggt caatatggaa caacttgcca ttgatggtgt 60tggctcccgt at 7258972DNAArtificial Sequencechemically synthesized 589atacgggagc caacaccaca ctaccgtccc accccctccc agctcctccg gccgagagca 60ggtgtgacgg at 7259072DNAArtificial Sequencechemically synthesized 590atccgtcaca cctgctctcg gccggaggag ctgggagggg gtgggacggt agtgtggtgt 60tggctcccgt at 7259172DNAArtificial Sequencechemically synthesized 591atacgggagc caacaccact caagtagtcc catacaccac gcaagcctct ctctagagca 60ggtgtgacgg at 7259272DNAArtificial Sequencechemically synthesized 592atccgtcaca cctgctctag agagaggctt gcgtggtgta tgggactact tgagtggtgt 60tggctcccgt at 7259372DNAArtificial Sequencechemically synthesized 593atacgggagc

caacaccaat cttactagtt tgggaaaaaa attaaatata agcaagagca 60ggtgtgacgg at 7259472DNAArtificial Sequencechemically synthesized 594atccgtcaca cctgctcttg cttatattta atttttttcc caaactagta agattggtgt 60tggctcccgt at 7259572DNAArtificial Sequencechemically synthesized 595atacgggagc caacaccaca ctaccgtccc accccctccc agctcctccg gccgagagca 60ggtgtgacgg at 7259672DNAArtificial Sequencechemically synthesized 596atccgtcaca cctgctctcg gccggaggag ctgggagggg gtgggacggt agtgtggtgt 60tggctcccgt at 7259772DNAArtificial Sequencechemically synthesized 597atacgggagc caacaccagc ctagctcgct cccaaaagag tccacgcccc ggatagagca 60ggtgtgacgg at 7259872DNAArtificial Sequencechemically synthesized 598atccgtcaca cctgctctat ccggggcgtg gactcttttg ggagcgagct aggctggtgt 60tggctcccgt at 7259972DNAArtificial Sequencechemically synthesized 599atacgggagc caacaccaac aaatttccag cgctatgggc cctaattacc actaagagca 60ggtgtgacgg at 7260072DNAArtificial Sequencechemically synthesized 600atccgtcaca cctgctctta gtggtaatta gggcccatag cgctggaaat ttgttggtgt 60tggctcccgt at 7260172DNAArtificial Sequencechemically synthesized 601atacgggagc caacaccacc tgccttacac ctttacactt ccgataaatt gccgagagca 60ggtgtgacgg at 7260272DNAArtificial Sequencechemically synthesized 602atccgtcaca cctgctctcg gcaatttatc ggaagtgtaa aggtgtaagg caggtggtgt 60tggctcccgt at 7260372DNAArtificial Sequencechemically synthesized 603atacgggagc caacaccata aagtcaattc caacgcagac catcctcacc cccaagagca 60ggtgtgacgg at 7260472DNAArtificial Sequencechemically synthesized 604atccgtcaca cctgctcttg ggggtgagga tggtctgcgt tggaattgac tttatggtgt 60tggctcccgt at 7260571DNAArtificial Sequencechemically synthesized 605atacgggagc caacaccaaa ggacgccccc cttcgtcccg cgctcggtag caaagagcag 60gtgtgacgga t 7160671DNAArtificial Sequencechemically synthesized 606atccgtcaca cctgctcttt gctaccgagc gcgggacgaa ggggggcgtc ctttggtgtt 60ggctcccgta t 7160772DNAArtificial Sequencechemically synthesized 607atacgggagc caacaccatg tcccttgggc acacacaacc aatccccact ctccagagca 60ggtgtgacgg at 7260872DNAArtificial Sequencechemically synthesized 608atccgtcaca cctgctctgg agagtgggga ttggttgtgt gtgcccaagg gacatggtgt 60tggctcccgt at 7260972DNAArtificial Sequencechemically synthesized 609atacgggagc caacaccacc ctgctggctt cggtccgttt catggtctgc aagcagagca 60ggtgtgacgg at 7261072DNAArtificial Sequencechemically synthesized 610atccgtcaca cctgctctgc ttgcagacca tgaaacggac cgaagccagc agggtggtgt 60tggctcccgt at 7261172DNAArtificial Sequencechemically synthesized 611atacgggagc caacaccaca ctaccgtccc accccctccc agctcctccg gccgagagca 60ggtgtgacgg ag 7261272DNAArtificial Sequencechemically synthesized 612atccgtcaca cctgctctcg gccggaggag ctgggagggg gtgggacggt agtgtggtgt 60tggctcccgt at 7261372DNAArtificial Sequencechemically synthesized 613atacgggagc caacaccatg ctgcgggacc gccatctacc tgttcatgtg tctgagagca 60ggtgtgacgg at 7261472DNAArtificial Sequencechemically synthesized 614atccgtcaca cctgctctca gacacatgaa caggtagatg gcggtcccgc agcatggtgt 60tggctcccgt at 7261571DNAArtificial Sequencechemically synthesized 615atacgggagc caacaccagg atgcggctta cattacgcct gtttgtcatc tggagagcag 60gtgtgacgga t 7161671DNAArtificial Sequencechemically synthesized 616atccgtcaca cctgctctcc agatgacaaa caggcgtaat gtaagccgca tcctggtgtt 60ggctcccgta t 7161772DNAArtificial Sequencechemically synthesized 617atacgggagc caacaccagt gccctggaga cggactgtcg gggatcgttc actcagagca 60ggtgtgacgg at 7261872DNAArtificial Sequencechemically synthesized 618atccgtcaca cctgctctga gtgaacgatc cccgacagtc cgtctccagg gcactggtgt 60tggctcccgt at 7261972DNAArtificial Sequencechemically synthesized 619atacgggagc caacaccata ttctgcctgg agatctagtc ccctgctctc ccacagagca 60ggtgtgacgg at 7262072DNAArtificial Sequencechemically synthesized 620atccgtcaca cctgctctgt gggagagcag gggactagat ctccaggcag aatatggtgt 60tggctcccgt at 7262172DNAArtificial Sequencechemically synthesized 621atacgggagc caacaccatc aagggcttca ctcataaatt attaatgtgt ccccagagca 60ggtgtgacgg at 7262272DNAArtificial Sequencechemically synthesized 622atccgtcaca cctgctctgg ggacacatta ataatttatg agtgaagccc ttgatggtgt 60tggctcccgt at 7262372DNAArtificial Sequencechemically synthesized 623atacgggagc caacaccacc cactctcccc ccgctcccgc tcctccgctc cgcgagagca 60ggtgtgacgg at 7262472DNAArtificial Sequencechemically synthesized 624atccgtcaca cctgctctcg cggagcggag gagcgggagc ggggggagag tgggtggtgt 60tggctcccgt at 7262572DNAArtificial Sequencechemically synthesized 625atacgggagc caacaccata tctatgtact accacaatca agttcttcct cactagagca 60ggtgtgacgg at 7262672DNAArtificial Sequencechemically synthesized 626atccgtcaca cctgctctag tgaggaagaa cttgattgtg gtagtacata gatatggtgt 60tggctcccgt at 7262772DNAArtificial Sequencechemically synthesized 627atacgggagc caacaccacc ttttaaaacg ctagctagct tagtccattc caccagagca 60ggtgtgacgg at 7262872DNAArtificial Sequencechemically synthesized 628atccgtcaca cctgctctgg tggaatggac taagctagct agcgttttaa aaggtggtgt 60tggctcccgt at 7262972DNAArtificial Sequencechemically synthesized 629atacgggagc caacaccatt agtgatcggt ggctcaaact tacgctcgct ccgaagagca 60ggtgtgacgg at 7263072DNAArtificial Sequencechemically synthesized 630atccgtcaca cctgctcttc ggagcgagcg taagtttgag ccaccgatca ctaatggtgt 60tggctcccgt at 7263172DNAArtificial Sequencechemically synthesized 631atacgggagc caacaccagt cgtggttcgc cgtttactga cgttccagtt gccaagagca 60ggtgtgacgg at 7263272DNAArtificial Sequencechemically synthesized 632atccgtcaca cctgctcttg gcaactggaa cgtcagtaaa cggcgaacca cgactggtgt 60tggctcccgt at 7263372DNAArtificial Sequencechemically synthesized 633atacgggagc caacaccaat ggttttccta cgacaagaat agaaaaattg ccgaagagca 60ggtgtgacgg at 7263472DNAArtificial Sequencechemically synthesized 634atccgtcaca cctgctcttc ggcaattttt ctattcttgt cgtaggaaaa ccattggtgt 60tggctcccgt at 7263572DNAArtificial Sequencechemically synthesized 635atacgggagc caacaccact tcatcttctg tactttattt ggcagacccc tcccagagca 60ggtgtgacgg at 7263672DNAArtificial Sequencechemically synthesized 636atccgtcaca cctgctctgg gaggggtctg ccaaataaag tacagaagat gaagtggtgt 60tggctcccgt at 7263771DNAArtificial Sequencechemically synthesized 637atacgggagc caacaccacc ttttaaaacg ctagctagct tatccattcc accagagcag 60gtgtgacgga t 7163871DNAArtificial Sequencechemically synthesized 638atccgtcaca cctgctctgg tggaatggat aagctagcta gcgttttaaa aggtggtgtt 60ggctcccgta t 7163972DNAArtificial Sequencechemically synthesized 639atacgggagc caacaccaga tagtgttcca ccttatacgg agccccctca ctgaagagca 60ggtgtgacgg at 7264072DNAArtificial Sequencechemically synthesized 640atccgtcaca cctgctcttc agtgaggggg ctccgtataa ggtggaacac tatctggtgt 60tggctcccgt at 7264172DNAArtificial Sequencechemically synthesized 641atacgggagc caacaccaac gcacatcagg agaatgaaga actcaccccc ccccagagca 60ggtgtgacgg at 7264272DNAArtificial Sequencechemically synthesized 642atccgtcaca cctgctctgg gggggggtga gttcttcatt ctcctgatgt gcgttggtgt 60tggctcccgt at 7264372DNAArtificial Sequencechemically synthesized 643atacgggagc caacaccact aacatgcgcg agggctctgt ccccgtccga catcagagca 60ggtgtgacgg at 7264472DNAArtificial Sequencechemically synthesized 644atccgtcaca cctgctctga tgtcggacgg ggacagagcc ctcgcgcatg ttagtggtgt 60tggctcccgt at 7264572DNAArtificial Sequencechemically synthesized 645atacgggagc caacaccaac ctggctatct gcatgcggtc ggtcgccttg ttggagagca 60ggtgtgacgg at 7264672DNAArtificial Sequencechemically synthesized 646atccgtcaca cctgctctcc aacaaggcga ccgaccgcat gcagatagcc aggttggtgt 60tggctcccgt at 7264772DNAArtificial Sequencechemically synthesized 647atacgggagc caacaccacg taccctcaac ctttaacttc tcataaccgg ctgtagagca 60ggtgtgacgg at 7264872DNAArtificial Sequencechemically synthesized 648atccgtcaca cctgctctac agccggttat gagaagttaa aggttgaggg tacgtggtgt 60tggctcccgt at 7264972DNAArtificial Sequencechemically synthesized 649atacgggagc caacaccatg cgtgcctaat gccggccatt ctactgcttg gcctagagca 60ggtgtgacgg at 7265072DNAArtificial Sequencechemically synthesized 650atccgtcaca cctgctctag gccaagcagt agaatggccg gcattaggca cgcatggtgt 60tggctcccgt at 7265172DNAArtificial Sequencechemically synthesized 651atacgggagc caacaccatg tgtactaatg tagctgttgc aacgttccta acttagagca 60ggtgtgacgg at 7265272DNAArtificial Sequencechemically synthesized 652atccgtcaca cctgctctaa gttaggaacg ttgcaacagc tacattagta cacatggtgt 60tggctcccgt at 7265372DNAArtificial Sequencechemically synthesized 653atacgggagc caacaccact ggtgaggcgc ctgcgccgac tggccgtccc cccgagagca 60ggtgtgacgg at 7265472DNAArtificial Sequencechemically synthesized 654atccgtcaca cctgctctcg gggggacggc cagtcggcgc aggcgcctca ccagtggtgt 60tggctcccgt at 7265572DNAArtificial Sequencechemically synthesized 655atacgggagc caacaccagg gggcctcgtt ctacgagcct gggtgtgtcc ctccagagca 60ggtgtgacgg at 7265672DNAArtificial Sequencechemically synthesized 656atccgtcaca cctgctctgg agggacacac ccaggctcgt agaacgaggc cccctggtgt 60tggctcccgt at 7265772DNAArtificial Sequencechemically synthesized 657atacgggagc caacaccatt gctgggccca cctatcggcg taccgaaccc ccgcagagca 60ggtgtgacgg at 7265872DNAArtificial Sequencechemically synthesized 658atccgtcaca cctgctctgc gggggttcgg tacgccgata ggtgggccca gcaatggtgt 60tggctcccgt at 7265972DNAArtificial Sequencechemically synthesized 659atacgggagc caacaccacg ccgggacccc cccacgatgg ctgcctatat gtccagagca 60ggtgtgacgg at 7266072DNAArtificial Sequencechemically synthesized 660atccgtcaca cctgctctgg acatataggc agccatcgtg ggggggtccc ggcgtggtgt 60tggctcccgt at 7266172DNAArtificial Sequencechemically synthesized 661atacgggagc caacaccacc ctacttatca tgtccttatc ccgccttact ggccagagca 60ggtgtgacgg at 7266272DNAArtificial Sequencechemically synthesized 662atccgtcaca cctgctctgg ccagtaaggc gggataagga catgataagt agggtggtgt 60tggctcccgt at 7266372DNAArtificial Sequencechemically synthesized 663atacgggagc caacaccatt accactcctt acttgtacgt gaccttgtac caccagagca 60ggtgtgacgg at 7266472DNAArtificial Sequencechemically synthesized 664atccgtcaca cctgctctgg tggtacaagg tcacgtacaa gtaaggagtg gtaatggtgt 60tggctcccgt at 7266572DNAArtificial Sequencechemically synthesized 665atacgggagc caacaccatt cctgctaact tgctgcctgc cctccacggg gctcagagca 60ggtgtgacgg at 7266672DNAArtificial Sequencechemically synthesized 666atccgtcaca cctgctctga gccccgtgga gggcaggcag caagttagca ggaatggtgt 60tggctcccgt at 7266772DNAArtificial Sequencechemically synthesized 667atacgggagc caacaccatc tcatggtagc tgcgctggtt ttgtgcgtga tattagagca 60ggtgtgacgg at 7266872DNAArtificial Sequencechemically synthesized 668atccgtcaca cctgctctaa tatcacgcac aaaaccagcg cagctaccat gagatggtgt 60tggctcccgt at 7266972DNAArtificial Sequencechemically synthesized 669atacgggagc caacaccatg taaactttca ggttggatag tacgggctca cacaagagca 60ggtgtgacgg at 7267072DNAArtificial Sequencechemically synthesized 670atccgtcaca cctgctcttg tgtgagcccg tactatccaa cctgaaagtt tacatggtgt 60tggctcccgt at 7267172DNAArtificial Sequencechemically synthesized 671atacgggagc caacaccatg tgtccgccct tgtttttgtg tcgtccggca atcgagagca 60ggtgtgacgg at 7267272DNAArtificial Sequencechemically synthesized 672atccgtcaca cctgctctcg attgccggac gacacaaaaa caagggcgga cacatggtgt 60tggctcccgt at 7267371DNAArtificial Sequencechemically synthesized 673atacgggagc caacaccagc agcataacgt ccgtatccca atccatgacg atcagagcag 60gtgtgacgga t 7167471DNAArtificial Sequencechemically synthesized 674atccgtcaca cctgctctga tcgtcatgga ttgggatacg gacgttatgc tgctggtgtt 60ggctcccgta t 7167572DNAArtificial Sequencechemically synthesized 675atacgggagc caacaccatt taggataagt ggtcacgccg tctcgattta actgagagca 60ggtgtgacgg at 7267672DNAArtificial Sequencechemically synthesized 676atccgtcaca cctgctctca gttaaatcga gacggcgtga ccacttatcc taaatggtgt 60tggctcccgt at

7267772DNAArtificial Sequencechemically synthesized 677atacgggagc caacaccaat tccgtatcca tgctctggct gcgtatcccc tttgagagca 60ggtgtgacgg at 7267872DNAArtificial Sequencechemically synthesized 678atccgtcaca cctgctctca aaggggatac gcagccagag catggatacg gaattggtgt 60tggctcccgt at 7267972DNAArtificial Sequencechemically synthesized 679atacgggagc caacaccagg aaccggaata gggaatcccc cttaccaacc ccccagagca 60ggtgtgacgg at 7268072DNAArtificial Sequencechemically synthesized 680atccgtcaca cctgctctgg ggggttggta agggggattc cctattccgg ttcctggtgt 60tggctcccgt at 7268172DNAArtificial Sequencechemically synthesized 681atacgggagc caacaccaga acaccgcccc ctgtctgttc caattgctgt tatcagagca 60ggtgtgacgg at 7268272DNAArtificial Sequencechemically synthesized 682atccgtcaca cctgctctga taacagcaat tggaacagac agggggcggt gttctggtgt 60tggctcccgt at 7268372DNAArtificial Sequencechemically synthesized 683atacgggagc caacaccacc cggttttaac ttttgttggt atgtctcgaa tcccagagca 60ggtgtgacgg at 7268472DNAArtificial Sequencechemically synthesized 684atccgtcaca cctgctctgg gattcgagac ataccaacaa aagttaaaac cgggtggtgt 60tggctcccgt at 7268571DNAArtificial Sequencechemically synthesized 685atacgggagc caacaccaaa tagagtattc gaaagtagcg tacttcaggt cctagagcag 60gtgtgacgga t 7168671DNAArtificial Sequencechemically synthesized 686atccgtcaca cctgctctag gacctgaagt acgctacttt cgaatactct atttggtgtt 60ggctcccgta t 7168770DNAArtificial Sequencechemically synthesized 687atacgggagc caacaccacc gaattgattg ataaaaaggg ttagatcgct ccagagcagg 60tgtgacggat 7068870DNAArtificial Sequencechemically synthesized 688atccgtcaca cctgctctgg agcgatctaa ccctttttat caatcaattc ggtggtgttg 60gctcccgtat 7068971DNAArtificial Sequencechemically synthesized 689atacgggagc caacaccatt ggcgacagag ttcgacgtcc cctagtggca gagagagcag 60gtgtgacgga t 7169071DNAArtificial Sequencechemically synthesized 690atccgtcaca cctgctctct ctgccactag gggacgtcga actctgtcgc caatggtgtt 60ggctcccgta t 7169172DNAArtificial Sequencechemically synthesized 691atacgggagc caacaccaat cgctctcaca aatttgccct agactcatac catcagagca 60ggtgtgacgg at 7269272DNAArtificial Sequencechemically synthesized 692atccgtcaca cctgctctga tggtatgagt ctagggcaaa tttgtgagag cgattggtgt 60tggctcccgt at 7269371DNAArtificial Sequencechemically synthesized 693atacgggagc ccacaccaca actttgaaga tccttgagcc gcgctcacca cctagagcag 60gtgtgacgga t 7169471DNAArtificial Sequencechemically synthesized 694atccgtcaca cctgctctag gtggtgagcg cggctcaagg atcttcaaag ttgtggtgtg 60ggctcccgta t 7169572DNAArtificial Sequencechemically synthesized 695atacgggagc caacaccaca aagtttagcg ttatgcaact cccccttata ctcgagagca 60ggtgtgacgg at 7269672DNAArtificial Sequencechemically synthesized 696atccgtcaca cctgctctcg agtataaggg ggagttgcat aacgctaaac tttgtggtgt 60tggctcccgt at 7269772DNAArtificial Sequencechemically synthesized 697atacgggagc caacaccaca aagtttagcg ttatgcaact cccccttata ctcgagagca 60ggtgtgacgg at 7269872DNAArtificial Sequencechemically synthesized 698atccgtcaca cctgctctcg agtataaggg ggagttgcat aacgctaaac tttgtggtgt 60tggctcccgt at 7269971DNAArtificial Sequencechemically synthesized 699atacgggagc caacaccata cggctatacc cgcccgacgt acaccacatc cccagagcag 60gtgtgacgga t 7170071DNAArtificial Sequencechemically synthesized 700atccgtcaca cctgctctgg ggatgtggtg tacgtcgggc gggtatagcc gtatggtgtt 60ggctcccgta t 7170172DNAArtificial Sequencechemically synthesized 701atacgggagc caacaccagt gtaacttgga gccctgacga gctcttcccg tagcagagca 60ggtgtgacgg at 7270272DNAArtificial Sequencechemically synthesized 702atccgtcaca cctgctctgc tacgggaaga gctcgtcagg gctccaagtt acactggtgt 60tggctcccgt at 7270372DNAArtificial Sequencechemically synthesized 703atacgggagc caacaccata gtttagcatg ctcaatagta caccagatca gtggagagca 60ggtgtgacgg at 7270472DNAArtificial Sequencechemically synthesized 704atccgtcaca cctgctctcc actgatctgg tgtactattg agcatgctaa actatggtgt 60tggctcccgt at 7270572DNAArtificial Sequencechemically synthesized 705atacgggagc caacaccatt cgtgtgtctg tctaagtgga actgcctgta attaagagca 60ggtgtgacgg at 7270672DNAArtificial Sequencechemically synthesized 706atccgtcaca cctgctctta attacaggca gttccactta gacagacaca cgaatggtgt 60tggctcccgt at 7270772DNAArtificial Sequencechemically synthesized 707atacgggagc caacaccaca tgagtggcgg gcttagcggg ctgcaaggcg cgttagagca 60ggtgtgacgg at 7270872DNAArtificial Sequencechemically synthesized 708atccgtcaca cctgctctaa cgcgccttgc agcccgctaa gcccgccact catgtggtgt 60tggctcccgt at 7270972DNAArtificial Sequencechemically synthesized 709atacgggagc caacaccatg tggcataaac agacgaattt gtcctataac gagtagagca 60ggtgtgacgg at 7271072DNAArtificial Sequencechemically synthesized 710atccgtcaca cctgctctac tcgttatagg acaaattcgt ctgtttatgc cacatggtgt 60tggctcccgt at 7271172DNAArtificial Sequencechemically synthesized 711atacgggagc caacaccact tattaccgat ttagcttgag actcctcccc tacaagagca 60ggtgtgacgg at 7271272DNAArtificial Sequencechemically synthesized 712atccgtcaca cctgctcttg taggggagga gtctcaagct aaatcggtaa taagtggtgt 60tggctcccgt at 7271372DNAArtificial Sequencechemically synthesized 713atacgggagc caacaccatc gttttgtact ttatgagccg cacggagccc ccccagagca 60ggtgtgacgg at 7271472DNAArtificial Sequencechemically synthesized 714atccgtcaca cctgctctgg gggggctccg tgcggctcat aaagtacaaa acgatggtgt 60tggctcccgt at 7271572DNAArtificial Sequencechemically synthesized 715atacgggagc caacaccatc tcgctaagct ctgttgggac taacttccgc tattagagca 60ggtgtgacgg at 7271672DNAArtificial Sequencechemically synthesized 716atccgtcaca cctgctctaa tagcggaagt tagtcccaac agagcttagc gagatggtgt 60tggctcccgt at 7271772DNAArtificial Sequencechemically synthesized 717atacgggagc caacaccatc caccctacgt cataatatga aatgaaacat atatagagca 60ggtgtgacgg at 7271872DNAArtificial Sequencechemically synthesized 718atccgtcaca cctgctctat atatgtttca tttcatatta tgacgtaggg tggatggtgt 60tggctcccgt at 7271972DNAArtificial Sequencechemically synthesized 719atacgggagc caacaccacc cactctcccc ccgctcccgc tcccccgctc cgcgagagca 60ggtgtgacgg at 7272072DNAArtificial Sequencechemically synthesized 720atccgtcaca cctgctctcg cggagcgggg gagcgggagc ggggggagag tgggtggtgt 60tggctcccgt at 7272172DNAArtificial Sequencechemically synthesized 721atacgggagc caacaccaat agttgcgtct tgtcatgtac gcctccttgc cagcagagca 60ggtgtgacgg at 7272272DNAArtificial Sequencechemically synthesized 722atccgtcaca cctgctctgc tggcaaggag gcgtacatga caagacgcaa ctattggtgt 60tggctcccgt at 7272372DNAArtificial Sequencechemically synthesized 723atacgggagc caacaccagc gggtttctta gttctgattg gacgctctgt ttgcagagca 60ggtgtgacgg at 7272472DNAArtificial Sequencechemically synthesized 724atccgtcaca cctgctctgc aaacagagcg tccaatcaga actaagaaac ccgctggtgt 60tggctcccgt at 7272572DNAArtificial Sequencechemically synthesized 725atacgggagc caacaccaag agcacctgca ccctcccgcc ctctattgca ttctagagca 60ggtgtgacgg at 7272672DNAArtificial Sequencechemically synthesized 726atccgtcaca cctgctctag aatgcaatag agggcgggag ggtgcaggtg ctcttggtgt 60tggctcccgt at 7272772DNAArtificial Sequencechemically synthesized 727atacgggagc caacaccaca tcataccttg ttctaccggc agcctctcta aataagagca 60ggtgtgacgg at 7272872DNAArtificial Sequencechemically synthesized 728atccgtcaca cctgctctta tttagagagg ctgccggtag aacaaggtat gatgtggtgt 60tggctcccgt at 7272972DNAArtificial Sequencechemically synthesized 729atacgggagc caacaccatt ccaaatgaac agttctcgat cccacttctc atctagagca 60ggtgtgacgg at 7273072DNAArtificial Sequencechemically synthesized 730atccgtcaca cctgctctag atgagaagtg ggatcgagaa ctgttcattt ggaatggtgt 60tggctcccgt at 7273172DNAArtificial Sequencechemically synthesized 731atacgggagc caacaccaga cctactgccc ccctgtctcc ctttgtctgc ccttagagca 60ggtgtgacgg at 7273272DNAArtificial Sequencechemically synthesized 732atccgtcaca cctgctctaa gggcagacaa agggagacag gggggcagta ggtctggtgt 60tggctcccgt at 7273372DNAArtificial Sequencechemically synthesized 733atacgggagc caacaccaac catcccggaa tgtgggtttt atgtaaatat aagcagagca 60ggtgtgacgg at 7273472DNAArtificial Sequencechemically synthesized 734atccgtcaca cctgctctgc ttatatttac ataaaaccca cattccggga tggttggtgt 60tggctcccgt at 7273572DNAArtificial Sequencechemically synthesized 735atacgggagc caacaccacc cctaactcct atatttaatc cttatcaaat ttctagagca 60ggtgtgacgg at 7273672DNAArtificial Sequencechemically synthesized 736atccgtcaca cctgctctag aaatttgata aggattaaat ataggagtta ggggtggtgt 60tggctcccgt at 7273772DNAArtificial Sequencechemically synthesized 737atacgggagc caacaccacc agcagtaaag ttccagcatt gcgcttaata gactagagca 60ggtgtgacgg at 7273872DNAArtificial Sequencechemically synthesized 738atccgtcaca cctgctctag tctattaagc gcaatgctgg aactttactg ctggtggtgt 60tggctcccgt at 7273972DNAArtificial Sequencechemically synthesized 739atacgggagc caacaccaag tccaagccaa acaagagcat aacaccaaat ctggagagca 60ggtgtgacgg at 7274072DNAArtificial Sequencechemically synthesized 740atccgtcaca cctgctctcc agatttggtg ttatgctctt gtttggcttg gacttggtgt 60tggctcccgt at 7274172DNAArtificial Sequencechemically synthesized 741atacgggagc caacaccact caatacgtct tatcgtctct gagtacatct ggccagagca 60ggtgtgacgg at 7274272DNAArtificial Sequencechemically synthesized 742atccgtcaca cctgctctgg ccagatgtac tcagagacga taagacgtat tgagtggtgt 60tggctcccgt at 7274372DNAArtificial Sequencechemically synthesized 743atacgggagc caacaccagg gccgctgcga tttctacgct acctgccgtt ggtaagagca 60ggtgtgacgg at 7274472DNAArtificial Sequencechemically synthesized 744atccgtcaca cctgctctta ccaacggcag gtagcgtaga aatcgcagcg gccctggtgt 60tggctcccgt at 7274572DNAArtificial Sequencechemically synthesized 745atacgggagc caacaccaca accggctaat gacaaatcaa agattttttc ggcgagagca 60ggtgtgacgg at 7274672DNAArtificial Sequencechemically synthesized 746atccgtcaca cctgctctcg ccgaaaaaat ctttgatttg tcattagccg gttgtggtgt 60tggctcccgt at 7274772DNAArtificial Sequencechemically synthesized 747atacgggagc caacaccagc acaacttaag tgcaagcaaa ttcggattaa ccaaagagca 60ggtgtgacgg at 7274872DNAArtificial Sequencechemically synthesized 748atccgtcaca cctgctcttt ggttaatccg aatttgcttg cacttaagtt gtgctggtgt 60tggctcccgt at 7274972DNAArtificial Sequencechemically synthesized 749atacgggagc caacaccatc cgaacagtta gtttaagacc gtcctccttt cttaagagca 60ggtgtgacgg at 7275072DNAArtificial Sequencechemically synthesized 750atccgtcaca cctgctctta agaaaggagg acggtcttaa actaactgtt cggatggtgt 60tggctcccgt at 7275172DNAArtificial Sequencechemically synthesized 751atacgggagc caacaccact tcaaaagtca gatacaaaga cagagattgg acttagagca 60ggtgtgacgg at 7275272DNAArtificial Sequencechemically synthesized 752atccgtcaca cctgctctaa gtccaatctc tgtctttgta tctgactttt gaagtggtgt 60tggctcccgt at 7275371DNAArtificial Sequencechemically synthesized 753atacgggagc caacaccact tccgttataa cgtttctgga atttactacg attagagcag 60gtgtgacgga t 7175471DNAArtificial Sequencechemically synthesized 754atccgtcaca cctgctctaa tcgtagtaaa ttccagaaac gttataacgg aagtggtgtt 60ggctcccgta t 7175571DNAArtificial Sequencechemically synthesized 755atacgggagc caacaccaac cacggatgtt gaatatccga cgatcacgta attagagcag 60gtgtgacgga t 7175671DNAArtificial Sequencechemically synthesized 756atccgtcaca cctgctctaa ttacgtgatc gtcggatatt caacatccgt ggttggtgtt 60ggctcccgta t 7175771DNAArtificial Sequencechemically synthesized 757atacgggagc caacaccata gacttaagct ctctccagga gcttgtcgct tgcagagcag 60gtgtgacgga t 7175871DNAArtificial Sequencechemically synthesized 758atccgtcaca cctgctctgc aagcgacaag ctcctggaga gagcttaagt ctatggtgtt 60ggctcccgta t 7175972DNAArtificial Sequencechemically synthesized 759atacgggagc caacaccacg ggggcatctt ccattaaccc attacctcac cccaagagca 60ggtgtgacgg at 7276072DNAArtificial Sequencechemically synthesized 760atccgtcaca cctgctcttg gggtgaggta atgggttaat ggaagatgcc cccgtggtgt 60tggctcccgt

at 7276171DNAArtificial Sequencechemically synthesized 761atacgggagc caacaccaca cagacaacca ttgattacgg ggacaattcg ggcagagcag 60gtgtgacgga t 7176271DNAArtificial Sequencechemically synthesized 762atccgtcaca cctgctctgc ccgaattgtc cccgtaatca atggttgtct gtgtggtgtt 60ggctcccgta t 7176371DNAArtificial Sequencechemically synthesized 763atacgggagc caacaccact ggtaggtgag tgtgtgtctg tactcgcatc gttagagcag 60gtgtgacgga t 7176471DNAArtificial Sequencechemically synthesized 764atccgtcaca cctgctctaa cgatgcgagt acagacacac actcacctac cagtggtgtt 60ggctcccgta t 7176570DNAArtificial Sequencechemically synthesized 765atacgggagc caacaccacc gaattgattg ataaaaaggg ttagatcgct ccagagcagg 60tgtgacggat 7076670DNAArtificial Sequencechemically synthesized 766atccgtcaca cctgctctgg agcgatctaa ccctttttat caatcaattc ggtggtgttg 60gctcccgtat 7076771DNAArtificial Sequencechemically synthesized 767atacgggagc caacaccacc taggccccca acatgtgtgg tataagtttc cgtagagcag 60gtgtgacgga t 7176871DNAArtificial Sequencechemically synthesized 768atccgtcaca cctgctctac ggaaacttat accacacatg ttgggggcct aggtggtgtt 60ggctcccgta t 7176971DNAArtificial Sequencechemically synthesized 769atacgggagc caacaccatc agaaactata gtgccatagt tttatctttg tacagagcag 60gtgtgacgga t 7177071DNAArtificial Sequencechemically synthesized 770atccgtcaca cctgctctgt acaaagataa aactatggca ctatagtttc tgatggtgtt 60ggctcccgta t 7177172DNAArtificial Sequencechemically synthesized 771atacgggagc caacaccaat agatggataa gggggaaact gccattcggt tagtagagca 60ggtgtgacgg at 7277272DNAArtificial Sequencechemically synthesized 772atccgtcaca cctgctctac taaccgaatg gcagtttccc ccttatccat ctattggtgt 60tggctcccgt at 7277372DNAArtificial Sequencechemically synthesized 773atacgggagc caacaccacc aacgaatact accaggccta gcacaataca caacagagca 60ggtgtgacgg at 7277472DNAArtificial Sequencechemically synthesized 774atccgtcaca cctgctctgt tgtgtattgt gctaggcctg gtagtattcg ttggtggtgt 60tggctcccgt at 7277571DNAArtificial Sequencechemically synthesized 775atacgggagc caacaccaaa cttgagatat gggcgctatg ttccttttca tccagagcag 60gtgtgacgga t 7177671DNAArtificial Sequencechemically synthesized 776atccgtcaca cctgctctgg atgaaaagga acatagcgcc catatctcaa gtttggtgtt 60ggctcccgta t 7177771DNAArtificial Sequencechemically synthesized 777atacgggagc caacaccagc cgaccggtaa gtttatataa acttccgccg cctagagcag 60gtgtgacgga t 7177871DNAArtificial Sequencechemically synthesized 778atccgtcaca cctgctctag gcggcggaag tttatataaa cttaccggtc ggctggtgtt 60ggctcccgta t 7177971DNAArtificial Sequencechemically synthesized 779atacgggagc caacaccatg actcacgctt ctcgcccgca cgaagagtct ccaagagcag 60gtgtgacgga t 7178071DNAArtificial Sequencechemically synthesized 780atccgtcaca cctgctcttg gagactcttc gtgcgggcga gaagcgtgag tcatggtgtt 60ggctcccgta t 7178171DNAArtificial Sequencechemically synthesized 781atacgggagc caacaccatg acgaccatgc aagaaatccg acaattcctc acgagagcag 60gtgtgacgga t 7178271DNAArtificial Sequencechemically synthesized 782atccgtcaca cctgctctcg tgaggaattg tcggatttct tgcatggtcg tcatggtgtt 60ggctcccgta t 7178371DNAArtificial Sequencechemically synthesized 783atacgggagc caacaccaag catttagatt cgctccttga acccacttcc ttcagagcag 60gtgtgacgga t 7178471DNAArtificial Sequencechemically synthesized 784atccgtcaca cctgctctga aggaagtggg ttcaaggagc gaatctaaat gcttggtgtt 60ggctcccgta t 7178571DNAArtificial Sequencechemically synthesized 785atacgggagc caacaccagg tgcttctctt acgtggccgc tattccaaag tgaagagcag 60gtgtgacgga t 7178671DNAArtificial Sequencechemically synthesized 786atccgtcaca cctgctcttc actttggaat agcggccacg taagagaagc acctggtgtt 60ggctcccgta t 7178771DNAArtificial Sequencechemically synthesized 787atacgggagc caacaccagc ccgggcatgt cgtttgtatg aagctagcta actagagcag 60gtgtgacgga t 7178871DNAArtificial Sequencechemically synthesized 788atccgtcaca cctgctctag ttagctagct tcatacaaac gacatgcccg ggctggtgtt 60ggctcccgta t 7178971DNAArtificial Sequencechemically synthesized 789atacgggagc caacaccatg accatcaata cagacaaata gaatcgcgtt atgagagcag 60gtgtgacgga t 7179071DNAArtificial Sequencechemically synthesized 790atccgtcaca cctgctctca taacgcgatt ctatttgtct gtattgatgg tcatggtgtt 60ggctcccgta t 7179172DNAArtificial Sequencechemically synthesized 791atacgggagc caacaccatg agggtttcct cacatgggga ggtcctccat gtggagagca 60ggtgtgacgg at 7279272DNAArtificial Sequencechemically synthesized 792atccgtcaca cctgctctcc acatggagga cctccccatg tgaggaaacc ctcatggtgt 60tggctcccgt at 7279371DNAArtificial Sequencechemically synthesized 793atacgggagc caacaccagg actaacatta taagaattgc gaataatcat tggagagcag 60gtgtgacgga t 7179471DNAArtificial Sequencechemically synthesized 794atccgtcaca cctgctctcc aatgattatt cgcaattctt ataatgttag tcctggtgtt 60ggctcccgta t 7179571DNAArtificial Sequencechemically synthesized 795atacgggagc caacaccatt gtaccttaac tatactcagc tacattatgc caaagagcag 60gtgtgacgga t 7179671DNAArtificial Sequencechemically synthesized 796atccgtcaca cctgctcttt ggcataatgt agctgagtat agttaaggta caatggtgtt 60ggctcccgta t 7179771DNAArtificial Sequencechemically synthesized 797atacgggagc caacaccact catgttggat attacgaaca gtgcgttagg ctgagagcag 60gtgtgacgga t 7179871DNAArtificial Sequencechemically synthesized 798atccgtcaca cctgctctca gcctaacgca ctgttcgtaa tatccaacat gagtggtgtt 60ggctcccgta t 7179971DNAArtificial Sequencechemically synthesized 799atacgggagc caacaccatg aacgcatcac agttgcttca cactcgacta gctagagcag 60gtgtgacgga t 7180071DNAArtificial Sequencechemically synthesized 800atccgtcaca cctgctctag ctagtcgagt gtgaagcaac tgtgatgcgt tcatggtgtt 60ggctcccgta t 7180171DNAArtificial Sequencechemically synthesized 801atacgggagc caacaccaaa aactactctc tacggatcgt acatcatggg cgtagagcag 60gtgtgacgga t 7180271DNAArtificial Sequencechemically synthesized 802atccgtcaca cctgctctac gcccatgatg tacgatccgt agagagtagt ttttggtgtt 60ggctcccgta t 7180372DNAArtificial Sequencechemically synthesized 803atacgggagc caacaccacc cactctcccc ccgctcccgc tcccccgctc cgcgagagca 60ggtgtgacgg at 7280472DNAArtificial Sequencechemically synthesized 804atccgtcaca cctgctctcg cggagcgggg gagcgggagc ggggggagag tgggtggtgt 60tggctcccgt at 7280571DNAArtificial Sequencechemically synthesized 805atacgggagc caacaccata gggcaattaa ggccaagagt gttggccgtc gctagagcag 60gtgtgacgga t 7180671DNAArtificial Sequencechemically synthesized 806atccgtcaca cctgctctag cgacggccaa cactcttggc cttaattgcc ctatggtgtt 60ggctcccgta t 7180771DNAArtificial Sequencechemically synthesized 807atacgggagc caacaccaaa acgggaaact gcatttccca cgcctcgtac cccagagcag 60gtgtgacgga t 7180871DNAArtificial Sequencechemically synthesized 808atccgtcaca cctgctctgg ggtacgaggc gtgggaaatg cagtttcccg ttttggtgtt 60ggctcccgta t 7180971DNAArtificial Sequencechemically synthesized 809atacgggagc caacaccaaa ccgaaggatc gccgggtcag acctatctca agcagagcag 60gtgtgacgga t 7181071DNAArtificial Sequencechemically synthesized 810atccgtcaca cctgctctgc ttgagatagg tctgacccgg cgatccttcg gtttggtgtt 60ggctcccgta t 7181171DNAArtificial Sequencechemically synthesized 811atacgggagc caacaccatt tgctgacgaa ccattggcta gcttgattgt cacagagcag 60gtgtgacgga t 7181271DNAArtificial Sequencechemically synthesized 812atccgtcaca cctgctctgt gacaatcaag ctagccaatg gttcgtcagc aaatggtgtt 60ggctcccgta t 7181371DNAArtificial Sequencechemically synthesized 813atacgggagc caacaccaga ctttttgctg ccatcccggg tgtcgttgca agtagagcag 60gtgtgacgga t 7181471DNAArtificial Sequencechemically synthesized 814atccgtcaca cctgctctac ttgcaacgac acccgggatg gcagcaaaaa gtctggtgtt 60ggctcccgta t 7181572DNAArtificial Sequencechemically synthesized 815atacgggagc caacaccacg catcccccgc cgggcccgcg ccccgctcgc agacagagca 60ggtgtgacgg at 7281672DNAArtificial Sequencechemically synthesized 816atccgtcaca cctgctctgt ctgcgagcgg ggcgcgggcc cggcggggga tgcgtggtgt 60tggctcccgt at 7281771DNAArtificial Sequencechemically synthesized 817atacgggagc caacaccaca atcattaaac ctttttactc ttcctgaatc accagagcag 60gtgtgacgga t 7181871DNAArtificial Sequencechemically synthesized 818atccgtcaca cctgctctgg tgattcagga agagtaaaaa ggtttaatga ttgtggtgtt 60ggctcccgta t 7181971DNAArtificial Sequencechemically synthesized 819atacgggagc caacaccaac ttatgcgacc cttccggtag ctggaggtta ttaagagcag 60gtgtgacgga t 7182071DNAArtificial Sequencechemically synthesized 820atccgtcaca cctgctctta ataacctcca gctaccggaa gggtcgcata agttggtgtt 60ggctcccgta t 7182172DNAArtificial Sequencechemically synthesized 821atacgggagc caacaccagg gccgcctctt tccgattcgt gggagccttc ttgaagagca 60ggtgtgacgg at 7282272DNAArtificial Sequencechemically synthesized 822atccgtcaca cctgctcttc aagaaggctc ccacgaatcg gaaagaggcg gccctggtgt 60tggctcccgt at 7282372DNAArtificial Sequencechemically synthesized 823atacgggagc caacaccatg ttccgtcaca ggtctcctgt tcttaatttg ttttagagca 60ggtgtgacgg at 7282472DNAArtificial Sequencechemically synthesized 824atccgtcaca cctgctctaa aacaaattaa gaacaggaga cctgtgacgg aacatggtgt 60tggctcccgt at 7282571DNAArtificial Sequencechemically synthesized 825atacgggagc caacaccata cgacctggaa actgctcgtc agagtctgaa atgagagcag 60gtgtgacgga t 7182671DNAArtificial Sequencechemically synthesized 826atccgtcaca cctgctctca tttcagactc tgacgagcag tttccaggtc gtatggtgtt 60ggctcccgta t 7182771DNAArtificial Sequencechemically synthesized 827atacgggagc caacaccaag ttgtcactgg atgacattcg ggttcgcttg cacagagcag 60gtgtgacgga t 7182871DNAArtificial Sequencechemically synthesized 828atccgtcaca cctgctctgt gcaagcgaac ccgaatgtca tccagtgaca acttggtgtt 60ggctcccgta t 7182971DNAArtificial Sequencechemically synthesized 829atacgggagc caacaccaaa gtggattgcg acgtgcttct accagatacc cggagagcag 60gtgtgacgga t 7183071DNAArtificial Sequencechemically synthesized 830atccgtcaca cctgctctcc gggtatctgg tagaagcacg tcgcaatcca ctttggtgtt 60ggctcccgta t 7183171DNAArtificial Sequencechemically synthesized 831atacgggagc caacaccagc acacggcacg cccctccgaa ccacgccccc gaaagagcag 60gtgtgacgga t 7183271DNAArtificial Sequencechemically synthesized 832atccgtcaca cctgctcttt cgggggcgtg gttcggaggg gcgtgccgtg tgctggtgtt 60ggctcccgta t 7183371DNAArtificial Sequencechemically synthesized 833atacgggagc caacaccagc gacgacagtt atataatccg agaatagtac atgagagcag 60gtgtgacgga t 7183471DNAArtificial Sequencechemically synthesized 834atccgtcaca cctgctctca tgtactattc tcggattata taactgtcgt cgctggtgtt 60ggctcccgta t 7183570DNAArtificial Sequencechemically synthesized 835atacgggagc caacaccagc acacggcacg ccccccgaac cacgcccccg aaagagcagg 60tgtgacggat 7083670DNAArtificial Sequencechemically synthesized 836atccgtcaca cctgctcttt cgggggcgtg gttcgggggg cgtgccgtgt gctggtgttg 60gctcccgtat 7083771DNAArtificial Sequencechemically synthesized 837atacgggagc caacaccata tttcaatctg ttgaaataat tcatacatgc ttaagagcag 60gtgtgacgga t 7183871DNAArtificial Sequencechemically synthesized 838atccgtcaca cctgctctta agcatgtatg aattatttca acagattgaa atatggtgtt 60ggctcccgta t 7183972DNAArtificial Sequencechemically synthesized 839atacgggagc caacaccatc ctcctgcgac gtctggagaa cagcctctac tttaagagca 60ggtgtgacgg at 7284072DNAArtificial Sequencechemically synthesized 840atccgtcaca cctgctctta aagtagaggc tgttctccag acgtcgcagg aggatggtgt 60tggctcccgt at 7284171DNAArtificial Sequencechemically synthesized 841atacgggagc caacaccagg ctgcgtacat gaacaggcac tacaaatgtc ccaagagcag 60gtgtgacgga t 7184271DNAArtificial Sequencechemically synthesized 842atccgtcaca cctgctcttg ggacatttgt agtgcctgtt catgtacgca gcctggtgtt 60ggctcccgta t 7184372DNAArtificial Sequencechemically synthesized 843atacgggagc caacaccaca gagagaagta cgtaacatca aaaacgcggt cagaagagca 60ggtgtgacgg at 7284472DNAArtificial Sequencechemically synthesized 844atccgtcaca

cctgctcttc tgaccgcgtt tttgatgtta cgtacttctc tctgtggtgt 60tggctcccgt at 7284570DNAArtificial Sequencechemically synthesized 845atacgggagc caacaccaac acaaccgagc caatagacaa tcagtgtttc acagagcagg 60tgtgacggat 7084670DNAArtificial Sequencechemically synthesized 846atccgtcaca cctgctctgt gaaacactga ttgtctattg gctcggttgt gttggtgttg 60gctcccgtat 7084772DNAArtificial Sequencechemically synthesized 847atacgggagc caacaccacc ctaaattcca gagtgtacaa gagaacgaac taccagagca 60ggtgtgacgg at 7284872DNAArtificial Sequencechemically synthesized 848atccgtcaca cctgctctgg tagttcgttc tcttgtacac tctggaattt agggtggtgt 60tggctcccgt at 7284972DNAArtificial Sequencechemically synthesized 849atacgggagc caacaccaat agatggataa gggggaaact gccattcggt tagtagagca 60ggtgtgacgg at 7285072DNAArtificial Sequencechemically synthesized 850atccgtcaca cctgctctac taaccgaatg gcagtttccc ccttatccat ctattggtgt 60tggctcccgt at 7285172DNAArtificial Sequencechemically synthesized 851atacgggagc caacaccaaa acccgcacta catctcctct gcccccttct gataagagca 60ggtgtgacgg at 7285272DNAArtificial Sequencechemically synthesized 852atccgtcaca cctgctctta tcagaagggg gcagaggaga tgtagtgcgg gttttggtgt 60tggctcccgt at 7285369DNAArtificial Sequencechemically synthesized 853atacgggagc caacaccatc gaatggtctc ccaactaaag aaactctcca tccagagcag 60gtgtgacgg 6985469DNAArtificial Sequencechemically synthesized 854ccgtcacacc tgctctggat ggagagtttc tttagttggg agaccattcg atggtgttgg 60ctcccgtat 6985572DNAArtificial Sequencechemically synthesized 855atacgggagc caacaccacg ggggcatctt ccattaaccc attacctcac cccaagagca 60ggtgtgacgg at 7285672DNAArtificial Sequencechemically synthesized 856atccgtcaca cctgctcttg gggtgaggta atgggttaat ggaagatgcc cccgtggtgt 60tggctcccgt at 7285771DNAArtificial Sequencechemically synthesized 857atacgggagc caacaccatg gacgtactga ctgccccgta ctcttttcag ttgagagcag 60gtgtgacgga t 7185871DNAArtificial Sequencechemically synthesized 858atccgtcaca cctgctctca actgaaaaga gtacggggca gtcagtacgt ccatggtgtt 60ggctcccgta t 7185971DNAArtificial Sequencechemically synthesized 859atacgggagc caacaccaac taactactca agatgaacac tgtcggcgtt tacagagcag 60gtgtgacgga t 7186071DNAArtificial Sequencechemically synthesized 860atccgtcaca cctgctctgt aaacgccgac agtgttcatc ttgagtagtt agttggtgtt 60ggctcccgta t 7186171DNAArtificial Sequencechemically synthesized 861atacgggagc caacaccagc ccttaagcgt tgcctaacgg actctgaggc aatagagcag 60gtgtgacgga t 7186271DNAArtificial Sequencechemically synthesized 862atccgtcaca cctgctctat tgcctcagag tccgttaggc aacgcttaag ggctggtgtt 60ggctcccgta t 7186371DNAArtificial Sequencechemically synthesized 863atacgggagc caacaccaac ctcacttaca actcgatttt ttatggacag ccgagagcag 60gtgtgacgga t 7186471DNAArtificial Sequencechemically synthesized 864atccgtcaca cctgctctcg gctgtccata aaaaatcgag ttgtaagtga ggttggtgtt 60ggctcccgta t 7186572DNAArtificial Sequencechemically synthesized 865atacgggagc caacaccatt tgagcggcag ctaaccggcc gaccaattcg ctacagagca 60ggtgtgacgg at 7286672DNAArtificial Sequencechemically synthesized 866atccgtcaca cctgctctgt agcgaattgg tcggccggtt agctgccgct caaatggtgt 60tggctcccgt at 7286772DNAArtificial Sequencechemically synthesized 867atacgggagc caacaccacc ttttaaaacg ctagctagct tagtccattc caccagagca 60ggtgtgacgg at 7286872DNAArtificial Sequencechemically synthesized 868atccgtcaca cctgctctgg tggaatggac taagctagct agcgttttaa aaggtggtgt 60tggctcccgt at 7286972DNAArtificial Sequencechemically synthesized 869atacgggagc caacaccagc cctgggccag cccgtgactt tcccccggcg tccaagagca 60ggtgtgacgg at 7287072DNAArtificial Sequencechemically synthesized 870atccgtcaca cctgctcttg gacgccgggg gaaagtcacg ggctggccca gggctggtgt 60tggctcccgt at 7287172DNAArtificial Sequencechemically synthesized 871atacgggagc caacaccatc ctcctgcggc gtctggagaa cagcctctac tttaagagca 60ggtgtgacgg at 7287272DNAArtificial Sequencechemically synthesized 872atccgtcaca cctgctctta aagtagaggc tgttctccag acgccgcagg aggatggtgt 60tggctcccgt at 7287372DNAArtificial Sequencechemically synthesized 873atacgggagc caacaccacc aacgaatact accaggccta gcacaataca caacagagca 60ggtgtgacgg at 7287472DNAArtificial Sequencechemically synthesized 874atccgtcaca cctgctctgt tgtgtattgt gctaggcctg gtagtattcg ttggtggtgt 60tggctcccgt at 7287572DNAArtificial Sequencechemically synthesized 875atacgggagc caacaccacc gaatgtgctg caagactaat ctggatggcc atgcagagca 60ggtgtgacgg at 7287672DNAArtificial Sequencechemically synthesized 876atccgtcaca cctgctctgc atggccatcc agattagtct tgcagcacat tcggtggtgt 60tggctcccgt at 7287771DNAArtificial Sequencechemically synthesized 877atacgggagc caacaccatt gaggggctgg gatactgcaa cttaaagtcc aggagagcag 60gtgtgacgga t 7187871DNAArtificial Sequencechemically synthesized 878atccgtcaca cctgctctcc tggactttaa gttgcagtat cccagcccct caatggtgtt 60ggctcccgta t 7187971DNAArtificial Sequencechemically synthesized 879atacgggagc caacaccaat aagcgactag tgtattggta ctggcctttt ccgagagcag 60gtgtgacgga t 7188071DNAArtificial Sequencechemically synthesized 880atccgtcaca cctgctctcg gaaaaggcca gtaccaatac actagtcgct tattggtgtt 60ggctcccgta t 7188172DNAArtificial Sequencechemically synthesized 881atacgggagc caacaccaat cttactagtt tgggaaaaaa attaaatata agcaagagca 60ggtgtgacgg at 7288272DNAArtificial Sequencechemically synthesized 882atccgtcaca cctgctcttg cttatattta atttttttcc caaactagta agattggtgt 60tggctcccgt at 7288372DNAArtificial Sequencechemically synthesized 883atacgggagc caacaccagt ccgttatgac atgtccggac ccgtacgcgt gtcaagagca 60ggtgtgacgg at 7288472DNAArtificial Sequencechemically synthesized 884atccgtcaca cctgctcttg acacgcgtac gggtccggac atgtcataac ggactggtgt 60tggctcccgt at 7288571DNAArtificial Sequencechemically synthesized 885atacgggagc caacaccagg gattgcatta cccatgacta agagtaggtc gcaagagcag 60gtgtgacgga t 7188671DNAArtificial Sequencechemically synthesized 886atccgtcaca cctgctcttg cgacctactc ttagtcatgg gtaatgcaat ccctggtgtt 60ggctcccgta t 7188772DNAArtificial Sequencechemically synthesized 887atacgggagc caacaccata gaagtatgtt gttattctat ggaaataaaa cgacagagca 60ggtgtgacgg at 7288872DNAArtificial Sequencechemically synthesized 888atccgtcaca cctgctctgt cgttttattt ccatagaata acaacatact tctatggtgt 60tggctcccgt at 7288972DNAArtificial Sequencechemically synthesized 889atacgggagc caacaccatc ccgttgtgat cagagagcat gaaatgatgt tttgagagca 60ggtgtgacgg at 7289072DNAArtificial Sequencechemically synthesized 890atccgtcaca cctgctctca aaacatcatt tcatgctctc tgatcacaac gggatggtgt 60tggctcccgt at 7289172DNAArtificial Sequencechemically synthesized 891atacgggagc caacaccatg catgggacct gttatcctaa caagctgtca aggcagagca 60ggtgtgacgg at 7289272DNAArtificial Sequencechemically synthesized 892atccgtcaca cctgctctgc cttgacagct tgttaggata acaggtccca tgcatggtgt 60tggctcccgt at 7289371DNAArtificial Sequencechemically synthesized 893atacgggagc caacaccaca aaacgttccg agggagtaag cacttaataa tgtagagcag 60gtgtgacgga t 7189471DNAArtificial Sequencechemically synthesized 894atccgtcaca cctgctctac attattaagt gcttactccc tcggaacgtt ttgtggtgtt 60ggctcccgta t 7189572DNAArtificial Sequencechemically synthesized 895atacgggagc caacaccacg tcttatagat gtctgtattg tttatcgctc gcccagagca 60ggtgtgacgg at 7289672DNAArtificial Sequencechemically synthesized 896atccgtcaca cctgctctgg gcgagcgata aacaatacag acatctataa gacgtggtgt 60tggctcccgt at 7289772DNAArtificial Sequencechemically synthesized 897atacgggagc caacaccacc atctctggtg ataaccagtg atcttaacta tagcagagca 60ggtgtgacgg at 7289872DNAArtificial Sequencechemically synthesized 898atccgtcaca cctgctctgc tatagttaag atcactggtt atcaccagag atggtggtgt 60tggctcccgt at 7289972DNAArtificial Sequencechemically synthesized 899atacgggagc caacaccacc acctcactac agtgatcttt tgctctgaat agccagagca 60ggtgtgacgg at 7290072DNAArtificial Sequencechemically synthesized 900atccgtcaca cctgctctgg ctattcagag caaaagatca ctgtagtgag gtggtggtgt 60tggctcccgt at 7290172DNAArtificial Sequencechemically synthesized 901atacgggagc caacaccatg tctcttagga tacaaagcca aactgagccc gtgcagagca 60ggtgtgacgg at 7290272DNAArtificial Sequencechemically synthesized 902atccgtcaca cctgctctgc acgggctcag tttggctttg tatcctaaga gacatggtgt 60tggctcccgt at 7290372DNAArtificial Sequencechemically synthesized 903atacgggagc caacaccacc tccaatagcc aaaagaaatc gccaactaac ggcaagagca 60ggtgtgacgg at 7290472DNAArtificial Sequencechemically synthesized 904atccgtcaca cctgctcttg ccgttagttg gcgatttctt ttggctattg gaggtggtgt 60tggctcccgt at 7290572DNAArtificial Sequencechemically synthesized 905atacgggagc caacaccatc actactttta taatttcatt cttctggcgt ccctagagca 60ggtgtgacgg at 7290672DNAArtificial Sequencechemically synthesized 906atccgtcaca cctgctctag ggacgccaga agaatgaaat tataaaagta gtgatggtgt 60tggctcccgt at 72

Claims

1. A DNA ligand sequence consisting of SEQ ID NO.: 4.

2. A DNA ligand sequence consisting of SEQ ID NO.: 434.

3. A DNA ligand sequence consisting of SEQ ID No.: 462.