Method and reagent for the inhibition of calcium activated chloride channel-1 (CLCA-1)

Abstract
Nucleic acid molecules, including antisense and enzymatic nucleic acid molecules, such as hammerhead ribozymes, DNAzymes, and GeneBlocs, which modulate the expression of calcium activated chloride channels (CLCA1, CLCA2, CLCA3, and CLCA4).
Description


BACKGROUND OF THE INVENTION

[0001] The present invention concerns compounds, compositions, and methods for the study, diagnosis, and treatment of conditions and diseases related to the expression of CLCA (Cl Channel Ca2+-Activated) genes.


[0002] The following is a brief description of the current understanding of CLCAs.


[0003] The discussion is not meant to be complete and is provided only for understanding the invention that follows. The summary is not an admission that any of the work described below is prior art to the claimed invention.


[0004] CLCA proteins are emerging as a new class of channel proteins that mediate Ca2+-activated Cl conductance in a variety of tissues. Members of the CLCA family have been cloned, isolated, and partially characterized from human, bovine, and murine species. These proteins demonstrate a high degree of homology in their size, sequence, and predicted structure yet can vary considerably in tissue distribution. Bovine CLCA1 (bCLCA1 or CaCC) was the first reported CLCA homolog. The bCLCA1 protein, which was isolated from and is exclusively detected in trachial epithelial cells, functions as a Ca2+-activated Cl channel (Ran and Benos, 1992, J Biol. Chem., 267, 3618-3625; Cunningham et al., 1995, J. Biol. Cherm, 270, 31016-31026). Another bovine homolog, bovine lung-endothelial cell adhesion molecule-1 (Lu-ECAM-1), appears to have involvement in the preferential metastasis of melanoma cells to the lung. Lu-ECAM-1 shares 92% nucleotide identity to bCLCA1 and is expressed in vascular endothelial cells (Elble et al., 1997, J. Biol. Chem., 272, 27853-27861). It has been shown that Lu-ECAM-1, can mediate the binding of lung-metastatic mouse B 16F 10 melanoma cells to endothelial cells (Zhu et al., 1992, J. Clin. Invest., 89, 1718-1724), however, due to sequence similarity to bCLCA1, the role of Lu-ECAM-1 as a chloride channel has been suggested (Elble et al., supra). The mouse homolog, mCLCA1, appears to have an expression pattern similar to the cystic fibrosis transmembrane conductance regulator (CFTR), with expression seen in various secretory epithelial cells, squamous epithelia, and in some lymphocytes (Gruber et al., 1998, Histochem. Cell Biol., 110,43-49).


[0005] The three human CLCA homologs (hCLCA1, hCLCA2, and hCLCA3) thus far cloned, isolated, and partially characterized, all retain sequence homology, similar cDNA length, and are all located on the short arm of chromosome 1 (tp22-p31). Human CLCA proteins show a restricted pattern of expression in differing secretory tissues. Human CLCA1 was the first reported calcium activated chloride channel in humans. The 31,902-bp hCLCA1 gene is located on chromosome 1p22-p31, contains 14 introns, and is preceded by a canonic promoter region that contains an LI transposable element. Expression of hCLCA1 is predominant in intestinal basal crypt epithelia and goblet cells. A protein processing model has been proposed for hCLCA1 in which the primary translation product (125-kDa) is cleaved to a 90-kDa and a group of 37- to 41-kDa proteins, the latter apparently representing different glycosylation products of the same polypeptide (Gruber et al., 1998, Genomics, 54, 200-214). Transient expression of hCLCA1 cDNA in HEK 293 cells is associated with an increase in whole-cell Ca2+-activated Cl conductance that is susceptible to inhibition with anion channel blocking compounds. Cell attached patch recordings of transfected cells in this study revealed single channels with a slope conductance of 13.4 pS (Gruber et al., supra).


[0006] The hCLCA2 homolog is processed in a similar manner as is hCLCA1, resulting in the formation of a heterodimer consisting of a 90-kDa amino terminal and an approximately 35-kDa carboxy terminal subunit with anchorage to the plasma membrane via four or five transmembrane domains. Expression of hCLCA2 is somewhat less restricted than that of hCLCA1, being expressed from human lung, trachea, and breast tissue (Gruber et al., 1999, Am. J. Physiol., 276, C1261-C1270). Human CLCA2 is expressed in normal breast epithelium but not in breast tumors of different stages of progression, suggesting that hCLCA2 may act as a tumor suppressor in breast cancer (Gruber et al., 1999, Cancer Res., 59, 5488-5491). Human CLCA3 is a truncated, secreted member of the CLCA family which is expressed in numerous tissues including lung, trachea, spleen, thymus, and breast tissue. Unlike hCLCA1 and hCLCA2 which are processed into heterodimers, hCLCA3 mRNA encodes a 37-kDa glycoprotein that corresponds to the N-terminal extracellular domain of its homologs. When hCLCA3 is expressed in HEK 293 or CHO cells, the 37-kDa glycoprotein is secreted (Gruber and Pauli, 1999, Biochem. Biophys. Acta, 1444, 418-423).


[0007] Holroyd et al., International PCT publication No. WO/9944620, describe a calcium-activated chloride channel that is induced by IL-9.



SUMMARY OF THE INVENTION

[0008] The invention features novel nucleic acid-based techniques [e.g., enzymatic nucleic acid molecules (ribozymes), antisense nucleic acids, 2-5A antisense chimeras, triplex DNA, antisense nucleic acids containing RNA cleaving chemical groups] and methods for their use to modulate the expression of CLCA (Cl Channel Ca2+-Activated) genes.


[0009] In a preferred embodiment, the invention features the use of one or more of the nucleic acid-based techniques independently or in combination to inhibit the expression of the genes encoding hCLCA1, hCLCA2, hCLCA3, and hCLCA4. Specifically, the invention features the use of nucleic acid-based techniques to specifically inhibit the expression of CLCA1 (GenBank accession Nos. NM001285, AF039400, AF039401, AF127036), CLCA2 (GenBank accession No. NM006536), CLCA3 (GenBank accession No. NM004921), and CLCA4 (GenBank accession No. NM012128) genes. In yet another preferred embodiment, the invention features the inhibition of CLCA1 gene using the nucleic acid-based techniques of the instant invention.


[0010] In another preferred embodiment, the invention features the use of an enzymatic nucleic acid molecule, preferably in the hammerhead, NCH (Inozyme), G-cleaver, amberzyme, zinzyme and/or DNAzyme motif, to inhibit the expression of CLCA genes.


[0011] By “inhibit” it is meant that the activity of CLCA1 or level of RNAs or equivalent RNAs encoding one or more protein subunits of CLCA1 is reduced below that observed in the absence of the nucleic acid molecules of the invention. In one embodiment, inhibition with enzymatic nucleic acid molecules preferably is below that level observed in the presence of an enzymatically inactive or attenuated molecule that is able to bind to the same site on the target RNA, but is unable to cleave that RNA. In another embodiment, inhibition with antisense oligonucleotides is preferably below that level observed in the presence of, for example, an oligonucleotide with scrambled sequence or with mismatches. In another embodiment, inhibition of CLCA1 genes with the nucleic acid molecule of the instant invention is greater than in the presence of the nucleic acid molecule than in its absence, or the presence of a control, irrelevant, or non-inhibitory oligonucleotide.


[0012] By “enzymatic nucleic acid molecule” it is meant a nucleic acid molecule which has complementarity in a substrate binding region to a specified gene target, and also has an enzymatic activity which is active to specifically cleave target RNA. That is, the enzymatic nucleic acid molecule is able to intermolecularly cleave RNA and thereby inactivate a target RNA molecule. These complementary regions allow sufficient hybridization of the enzymatic nucleic acid molecule to the target RNA and thus permit cleavage. One hundred percent complementarity is preferred, but complementarity as low as 50-75% may also be useful in this invention. The nucleic acids may be modified at the base, sugar, and/or phosphate groups. The term enzymatic nucleic acid is used interchangeably with phrases such as ribozymes, catalytic RNA, enzymatic RNA, catalytic DNA, aptazyme or aptamer-binding ribozyme, regulatable ribozyme, catalytic oligonucleotides, nucleozyme, DNAzyme, RNA enzyme, endoribonuclease, endonuclease, minizyme, leadzyme, oligozyme or DNA enzyme. All of these terminologies describe nucleic acid molecules with enzymatic activity. The specific enzymatic nucleic acid molecules described in the instant application are not meant to be limiting and those skilled in the art will recognize that all that is important in an enzymatic nucleic acid molecule of this invention is that it have a specific substrate binding site which is complementary to one or more of the target nucleic acid regions, and that it have nucleotide sequences within or surrounding that substrate binding site which impart a nucleic acid cleaving activity to the molecule (Cech et al., U.S. Pat. No. 4,987,071; Cech et al., 1988, JAMA).


[0013] By “nucleic acid molecule” as used herein is meant a molecule having nucleotides. The nucleic acid can be single, double, or multiple stranded and may comprise modified or unmodified nucleotides or non-nucleotides or various mixtures and combinations thereof.


[0014] By “enzymatic portion” or “catalytic domain” is meant that portion/region of the enzymatic nucleic acid molecule essential for cleavage of a nucleic acid substrate (for example, see FIGS. 1-4).


[0015] By “substrate binding arm” or “substrate binding domain” is meant that portion/region of a ribozyme which is complementary to (i.e., able to base-pair with) a portion of its substrate. Generally, such complementarity is 100%, but can be less if desired. For example, as few as 10 bases out of 14 may be base-paired. Examples of such arms are shown generally in FIGS. 1-4. That is, these arms contain sequences within a ribozyme which are intended to bring ribozyme and target RNA together through complementary base-pairing interactions. The ribozyme of the invention may have binding arms that are contiguous or non-contiguous and may be of varying lengths. The length of the binding arm(s) are preferably greater than or equal to four nucleotides and of sufficient length to stably interact with the target RNA; specifically 12-100 nucleotides; more specifically 14-24 nucleotides long. If two binding arms are chosen, the design is such that the length of the binding arms are symmetrical (i.e., each of the binding arms is of the same length; e.g., five and five nucleotides, six and six nucleotides or seven and seven nucleotides long) or asymmetrical (i.e., the binding arms are of different length; e.g., six and three nucleotides; three and six nucleotides long; four and five nucleotides long; four and six nucleotides long; four and seven nucleotides long; and the like).


[0016] By “NCH” or “Inozyme” motif is meant, an enzymatic nucleic acid molecule comprising a motif as described in Ludwig et al., U.S. Ser. No. 09/406,643, filed Sep. 27, 1999, entitled “COMPOSITIONS HAVING RNA CLEAVING ACTIVITY”, and International PCT publication Nos. WO 98/58058 and WO 98/58057, all incorporated by reference herein in their entirety including the drawings.


[0017] By “G-cleaver” motif is meant, an enzymatic nucleic acid molecule comprising a motif as described in Eckstein et al., International PCT publication No. WO 99/16871, incorporated by reference herein in its entirety including the drawings.


[0018] By “zinzyme” motif is meant, a class II enzymatic nucleic acid molecule comprising a motif as described in Beigelman et al., International PCT publication No. WO 99/55857, incorporated by reference herein in its entirety including the drawings. Zinzymes represent a non-limiting example of an enzymatic nucleic acid molecule that does not require a ribonucleotide (2′-OH) group within its own nucleic acid sequence for activity.


[0019] By “amberzyme” motif is meant, a class I enzymatic nucleic acid molecule comprising a motif as described in Beigelman et al., International PCT publication No. WO 99/55857, incorporated by reference herein in its entirety including the drawings. Amberzymes represent a non-limiting example of an enzymatic nucleic acid molecule that does not require a ribonucleotide (2′-OH) group within its own nucleic acid sequence for activity.


[0020] By ‘DNAzyme’ is meant, an enzymatic nucleic acid molecule that does not require the presence of a ribonucleotide (2′-OH) group within the DNAzyme molecule for its activity. In particular embodiments the enzymatic nucleic acid molecule may have an attached linker(s) or other attached or associated groups, moieties, or chains containing one or more nucleotides with 2′-OH groups.


[0021] DNAzyme can be synthesized chemically or expressed endogenously in vivo, by means of a single stranded DNA vector or equivalent thereof.


[0022] By “sufficient length” is meant an oligonucleotide of greater than or equal to 3 nucleotides that is of a length great enough to provide the intended function under the expected condition. For example, for binding arms of enzymatic nucleic acid “sufficient length” means that the binding arm sequence is long enough to provide stable binding to a target site under the expected binding conditions. Preferably, the binding arms are not so long as to prevent useful turnover.


[0023] By “stably interact” is meant, interaction of the oligonucleotides with target nucleic acid (e.g., by forming hydrogen bonds with complementary nucleotides in the target under physiological conditions).


[0024] By “equivalent” RNA to CLCA1 is meant to include those naturally occurring RNA molecules having homology (partial or complete) to CLCA1 proteins or encoding for proteins with similar function as CLCA1 in various organisms, including human, rodent, primate, rabbit, pig, protozoans, fungi, plants, and other microorganisms and parasites. The equivalent RNA sequence also includes in addition to the coding region, regions such as 5′-untranslated region, 3′-untranslated region, introns, intron-exon junction and the like.


[0025] By “homology” is meant the nucleotide sequence of two or more nucleic acid molecules is partially or completely identical.


[0026] By “antisense nucleic acid”, it is meant a non-enzymatic nucleic acid molecule that binds to target RNA by means of RNA-RNA or RNA-DNA or RNA-PNA (protein nucleic acid; Egholm et al., 1993 Nature 365, 566) interactions and alters the activity of the target RNA (for a review, see Stein and Cheng, 1993 25 Science 261, 1004 and Woolf et al, U.S. Pat. No. 5,849,902). Typically, antisense molecules will be complementary to a target sequence along a single contiguous sequence of the antisense molecule. However, in certain embodiments, an antisense molecule may bind to substrate such that the substrate molecule forms a loop, and/or an antisense molecule may bind such that the antisense molecule forms a loop. Thus, the antisense molecule may be complementary to two (or even more) non-contiguous substrate sequences or two (or even more) non-contiguous sequence portions of an antisense molecule may be complementary to a target sequence or both. For a review of current antisense strategies, see Schmajuk et al., 1999, J. Biol. Chem., 274, 21783-21789, Delihas et al., 1997, Nature, 15, 751-753, Stein et al., 1997, Antisense N. A. Drug Dev., 7, 151, Crooke, 1998, Biotech. Genet. Eng. Rev., 15, 121-157, Crooke, 1997, Ad. Pharmacol., 40, 1-49. In addition, antisense DNA can be used to target RNA by means of DNA-RNA interactions, thereby activating RNase H, which digests the target RNA in the duplex. Antisense DNA can be synthesized chemically or expressed via the use of a single stranded DNA expression vector or equivalent thereof.


[0027] By “2-5A antisense chimera” it is meant, an antisense oligonucleotide containing a 5′-phosphorylated 2′-5′-linked adenylate residue. These chimeras bind to target RNA in a sequence-specific manner and activate a cellular 2-5A-dependent ribonuclease which, in turn, cleaves the target RNA (Torrence et al., 1993 Proc. Natl. Acad. Sci. USA 90, 1300).


[0028] By “triplex DNA” it is meant an oligonucleotide that can bind to a double-stranded DNA in a sequence-specific manner to form a triple-strand helix. Formation of such triple helix structure has been shown to inhibit transcription of the targeted gene (Duval-Valentin et al., 1992 Proc. Natl. Acad. Sci. USA 89, 504).


[0029] By “gene” it is meant a nucleic acid that encodes an RNA.


[0030] By “complementarity” is meant that a nucleic acid can form hydrogen bond(s) with another RNA sequence by either traditional Watson-Crick or other non-traditional types. In reference to the nucleic molecules of the present invention, the binding free energy for a nucleic acid molecule with its target or complementary sequence is sufficient to allow the relevant function of the nucleic acid to proceed, e.g., ribozyme cleavage, antisense or triple helix inhibition. Determination of binding free energies for nucleic acid molecules is well known in the art (see, e.g., Turner et al., 1987, CSHSymp. Quant. Biol. LII pp.123-133; Frier et al., 1986, Proc. Nat. Acad. Sci. USA 83:9373-9377; Turner et al., 1987, J. Am. Chem. Soc. 109:3783-3785). A percent complementarity indicates the percentage of contiguous residues in a nucleic acid molecule which can form hydrogen bonds (e.g., Watson-Crick base pairing) with a second nucleic acid sequence (e.g., 5, 6, 7, 8, 9, 10 out of 10 being 50%, 60%, 70%, 80%, 90%, and 100% complementary). “Perfectly complementary” means that all the contiguous residues of a nucleic acid sequence will hydrogen bond with the same number of contiguous residues in a second nucleic acid sequence.


[0031] At least seven basic varieties of naturally occurring enzymatic nucleic acids are known presently. Each can catalyze the hydrolysis of RNA phosphodiester bonds in trans (and thus can cleave other RNA molecules) under physiological conditions. Table I summarizes some of the characteristics of these ribozymes. In general, enzymatic nucleic acids act by first binding to a target RNA. Such binding occurs through the target binding portion of a enzymatic nucleic acid which is held in close proximity to an enzymatic portion of the molecule that acts to cleave the target RNA. Thus, the enzymatic nucleic acid first recognizes and then binds a target RNA through complementary base-pairing, and once bound to the correct site, acts enzymatically to cut the target RNA. Strategic cleavage of such a target RNA will destroy its ability to direct synthesis of an encoded protein. After an enzymatic nucleic acid has bound and cleaved its RNA target, it is released from that RNA to search for another target and can repeatedly bind and cleave new targets. Thus, a single ribozyme molecule is able to cleave many molecules of target RNA. In addition, the ribozyme is a highly specific inhibitor of gene expression, with the specificity of inhibition depending not only on the base-pairing mechanism of binding to the target RNA, but also on the mechanism of target RNA cleavage. Single mismatches, or base-substitutions, near the site of cleavage can completely eliminate catalytic activity of a ribozyme.


[0032] The enzymatic nucleic acid molecule that cleave the specified sites in CLCA1-specific RNAs represent a novel therapeutic approach to treat Chronic Obstructive Pulmonary Diseases (COPDs), chronic bronchitis, asthma, cystic fibrosis, obstructive bowel syndrome, and other indications that may respond to the level of CLCA1.


[0033] In one of the preferred embodiments of the inventions described herein, the enzymatic nucleic acid molecule is formed in a hammerhead or hairpin motif, but may also be formed in the motif of a hepatitis delta virus, group I intron, group II intron or RNase P RNA (in association with an RNA guide sequence), Neurospora VS RNA, DNAzymes, NCH cleaving motifs, or G-cleavers. Examples of such hammerhead motifs are described by Dreyfus, supra, Rossi et al., 1992, AIDS Research and Human Retroviruses 8, 183; Examples of hairpin motifs are described by Hampel et al., EP0360257, Hampel and Tritz, 1989 Biochemistry 28, 4929, Feldstein et al., 1989, Gene 82, 53, Haseloff and Gerlach, 1989, Gene, 82, 43, Hampel et al., 1990 Nucleic Acids Res. 18, 299; Chowrira & McSwiggen, U.S. Pat. No. 5,631,359. The hepatitis delta virus motif is described by Perrotta and Been, 1992 Biochemistry 31, 16. The RNase P motif is described by Guerrier-Takada et al., 1983 Cell 35, 849; Forster and Altman, 1990, Science 249, 783; Li and Altman, 1996, Nucleic Acids Res. 24, 835. Neurospora VS RNA ribozyme motif is described by Collins (Saville and Collins, 1990 Cell 61, 685-696; Saville and Collins, 1991 Proc. Natl. Acad. Sci. USA 88, 8826-8830; Collins and Olive, 1993 Biochemistry 32, 2795-2799; Guo and Collins, 1995, EMBO. J. 14, 363). Group II introns are described by Griffin et al., 1995, Chem. Biol. 2, 761; Michels and Pyle, 1995, Biochemistry 34, 2965; Pyle et al., International PCT Publication No. WO 96/22689. The Group I intron is described by Cech et al., U.S. Pat. No. 4,987,071. DNAzymes are described by Usman et al., International PCT Publication No. WO 95/11304; Chartrand et al., 1995, NAR 23, 4092; Breaker et al., 1995, Chem. Bio. 2, 655; Santoro et al., 1997, PNAS 94, 4262. NCH cleaving motifs are described in Ludwig & Sproat, International PCT Publication No. WO 98/58058; and G-cleavers are described in Kore et al., 1998, Nucleic Acids Research 26, 4116-4120 and Eckstein et al., International PCT Publication No. WO 99/16871. Additional motifs such as the Aptazyme (Breaker et al., WO 98/43993), Amberzyme (Class I motif; FIG. 3; Beigelman et al., International PCT publication No. WO 99/55857) and Zinzyme (Beigelman et al., International PCT publication No. WO 99/55857), all these references are incorporated by reference herein in their totalities, including drawings and can also be used in the present invention. These specific motifs are not limiting in the invention, and those skilled in the art will recognize that all that is important in an enzymatic nucleic acid molecule of this invention is that it has a specific substrate binding site which is complementary to one or more of the target gene RNA regions, and that it have nucleotide sequences within or surrounding that substrate binding site which impart an RNA cleaving activity to the molecule (Cech et al., U.S. Pat. No. 4,987,071).


[0034] In preferred embodiments of the present invention, a nucleic acid molecule, e.g., an antisense molecule, a triplex DNA, or a ribozyme, is 13 to 100 nucleotides in length, e.g., in specific embodiments 35, 36, 37, or 38 nucleotides in length (e.g., for particular ribozymes or antisense). In particular embodiments, the nucleic acid molecule is 15-100, 17-100, 20-100, 21-100, 23-100, 25-100, 27-100, 30-100, 32-100, 35-100, 40-100, 50-100, 60-100, 70-100, or 80-100 nucleotides in length. Instead of 100 nucleotides being the upper limit on the length ranges specified above, the upper limit of the length range can be, for example, 30, 40, 50, 60, 70, or 80 nucleotides. Thus, for any of the length ranges, the length range for particular embodiments has lower limit as specified, with an upper limit as specified which is greater than the lower limit. For example, in a particular embodiment, the length range can be 35-50 nucleotides in length. All such ranges are expressly included. Also in particular embodiments, a nucleic acid molecule can have a length which is any of the lengths specified above, for example, 21 nucleotides in length.


[0035] In a preferred embodiment, the invention provides a method for producing a class of nucleic acid-based gene inhibiting agents which exhibit a high degree of specificity for the RNA of a desired target. For example, the enzymatic nucleic acid molecule is preferably targeted to a highly conserved sequence region of target RNAs encoding CLCA proteins (for example, CLCA1, CLCA2, CLCA3 and/or CLCA4) such that specific treatment of a disease or condition can be provided with either one or several nucleic acid molecules of the invention. Such nucleic acid molecules can be delivered exogenously to specific tissue or cellular targets as required. Alternatively, the nucleic acid molecules (e.g., ribozymes and antisense) can be expressed from DNA and/or RNA vectors that are delivered to specific cells.


[0036] In a preferred embodiment, the invention features the use of nucleic acid-based inhibitors of the invention to specifically target genes that share homology with the CLCA1 gene.


[0037] As used herein “cell” is used in its usual biological sense, and does not refer to an entire multicellular organism, e.g., specifically does not refer to a human. The cell may be present in a non-human multicellular organism, e.g., birds, plants and mammals such as cows, sheep, apes, monkeys, swine, dogs, and cats.


[0038] By “CLCA proteins” is meant, a protein or a mutant protein derivative thereof, comprising a calcium activated chloride channel protein.


[0039] By “highly conserved sequence region” is meant, a nucleotide sequence of one or more regions in a target gene does not vary significantly from one generation to the other or from one biological system to the other.


[0040] The nucleic acid-based inhibitors of CLCA1 expression are useful for the prevention and/or treatment of diseases and conditions including Chronic Obstructive Pulmonary Disease (COPD), chronic bronchitis, asthma, cystic fibrosis, obstructive bowel syndrome, and any other diseases or conditions that are related to or will respond to the levels of CLCA1 in a cell or tissue, alone or in combination with other therapies.


[0041] By “related” is meant that the reduction of CLCA1 expression (specifically CLCA1 gene) RNA levels and thus reduction in the level of the respective protein will relieve, to some extent, the symptoms of the disease or condition.


[0042] The nucleic acid-based inhibitors of the invention are added directly, or can be complexed with cationic lipids, packaged within liposomes, or otherwise delivered to target cells or tissues. The nucleic acid or nucleic acid complexes can be locally administered to relevant tissues ex vivo, or in vivo through injection, infusion pump or stent, with or without their incorporation in biopolymers. In preferred embodiments, the enzymatic nucleic acid inhibitors comprise sequences, which are complementary to the substrate sequences in Tables III to IX. Examples of such enzymatic nucleic acid molecules also are shown in Tables III to IX. Examples of such enzymatic nucleic acid molecules consist essentially of sequences defined in these Tables.


[0043] In yet another embodiment, the invention features antisense nucleic acid molecules and 2-5A chimera including sequences complementary to the substrate sequences shown in Tables III to IX. Such nucleic acid molecules can include sequences as shown for the binding arms of the enzymatic nucleic acid molecules in Tables III to VIII and sequences shown as GeneBloc™ sequences in Table IX. Similarly, triplex molecules can be provided targeted to the corresponding DNA target regions, and containing the DNA equivalent of a target sequence or a sequence complementary to the specified target (substrate) sequence. Typically, antisense molecules will be complementary to a target sequence along a single contiguous sequence of the antisense molecule. However, in certain embodiments, an antisense molecule may bind to substrate such that the substrate molecule forms a loop, and/or an antisense molecule may bind such that the antisense molecule forms a loop. Thus, the antisense molecule may be complementary to two (or even more) non-contiguous substrate sequences or two (or even more) non-contiguous sequence portions of an antisense molecule may be complementary to a target sequence or both.


[0044] By “consists essentially of” is meant that the active nucleic acid molecule of the invention, for example, an enzymatic nucleic acid molecule, contains an enzymatic center or core equivalent to those in the examples, and binding arms able to bind RNA such that cleavage at the target site occurs. Other sequences can be present which do not interfere with such cleavage. Thus, a core region can, for example, include one or more loop, stem-loop structure, or linker which does not prevent enzymatic activity. Thus, the underlined regions in the sequences in Tables III, IV and VIII can be such a loop, stem-loop, nucleotide linker, and/or non-nucleotide linker and can be represented generally as sequence “X”. For example, a core sequence for a hammerhead enzymatic nucleic acid can comprise a conserved sequence, such as 5′-CUGAUGAG-3′ and 5′-CGAA-3′ connected by “X”, where X is 5′-GCCGUUAGGC-3′ (SEQ ID NO 5450), or any other Stem II region known in the art.


[0045] In another aspect of the invention, ribozymes or antisense molecules that interact with target RNA molecules and inhibit CLCA1 (specifically CLCA1 gene) activity are expressed from transcription units inserted into DNA or RNA vectors. The recombinant vectors are preferably DNA plasmids or viral vectors. Ribozyme or antisense expressing viral vectors could be constructed based on, but not limited to, adeno-associated virus, retrovirus, adenovirus, or alphavirus. Preferably, the recombinant vectors capable of expressing the ribozymes or antisense are delivered as described above, and persist in target cells. Alternatively, viral vectors may be used that provide for transient expression of ribozymes or antisense. Such vectors can be repeatedly administered as necessary. Once expressed, the ribozymes or antisense bind to the target RNA and inhibit its function or expression. Delivery of ribozyme or antisense expressing vectors can be systemic, such as by intravenous or intramuscular administration, by administration to target cells ex-planted from the patient followed by reintroduction into the patient, or by any other means that would allow for introduction into the desired target cell. Antisense DNA can be expressed endogenously via the use of a single stranded DNA intracellular expression vector.


[0046] By RNA is meant a molecule comprising at least one ribonucleotide residue. By “ribonucleotide” is meant a nucleotide with a hydroxyl group at the 2′ position of a β-D-ribo-faranose moiety.


[0047] By “vectors” is meant any nucleic acid- and/or viral-based technique used to deliver a desired nucleic acid.


[0048] By “patient” is meant an organism, which is a donor or recipient of explanted cells or the cells themselves. “Patient” also refers to an organism to which the nucleic acid molecules of the invention can be administered. Preferably, a patient is a mammal or mammalian cells. More preferably, a patient is a human or human cells.


[0049] The nucleic acid molecules of the instant invention, individually, or in combination or in conjunction with other drugs, can be used to treat diseases or conditions discussed above. For example, to treat a disease or condition associated with the levels of CLCA1, the patient may be treated, or other appropriate cells may be treated, as is evident to those skilled in the art, individually or in combination with one or more drugs under conditions suitable for the treatment.


[0050] In a further embodiment, the described molecules, such as antisense or ribozymes, can be used in combination with other known treatments to treat conditions or diseases discussed above. For example, the described molecules could be used in combination with one or more known therapeutic agents to treat Chronic Obstructive Pulmonary Diseases (COPDs), chronic bronchitis, asthma, cystic fibrosis, obstructive bowel syndrome, and/or other disease states or conditions which respond to the modulation of CLCA1 expression.


[0051] In another preferred embodiment, the invention features nucleic acid-based inhibitors (e.g., enzymatic nucleic acid molecules (ribozymes), antisense nucleic acids, 2-5A antisense chimeras, triplex DNA, antisense nucleic acids containing RNA cleaving chemical groups) and methods for their use to down regulate or inhibit the expression of genes (e.g., CLCA1) capable of progression and/or maintenance of Chronic Obstructive Pulmonary Diseases (COPDs), chronic bronchitis, asthma, cystic fibrosis, obstructive bowel syndrome, and/or other disease states or conditions which respond to the modulation of CLCA1 expression.


[0052] By “comprising” is meant including, but not limited to, whatever follows the word “comprising”. Thus, use of the term “comprising” indicates that the listed elements are required or mandatory, but that other elements are optional and may or may not be present. By “consisting of” is meant including, and limited to, whatever follows the phrase “consisting of”. Thus, the phrase “consisting of” indicates that the And listed elements are required or mandatory, and that no other elements may be present. By “consisting essentially of” is meant including any elements listed after the phrase, and limited to other elements that do not interfere with or contribute to the activity or action specified in the disclosure for the listed elements. Thus, the phrase “consisting essentially of” indicates that the listed elements are required or mandatory, but that other elements are optional and may or may not be present depending upon whether or not they affect the activity or action of the listed elements.


[0053] The foregoing description of the various aspects and embodiments is provided with reference to the exemplary calcium activated chloride channel gene CLCA1, which is also referred to as CaCC1 or ICACC-1. However, the various aspects and embodiments are also directed to other genes which express CLCA1 or CaCC1-like proteins (for example hCLCA2, hCLCA3, hCLCA4, CaCC2, and CaCC3). Those additional genes can be analyzed for target sites using the methods described for CLCA1. Thus, the inhibition and the effects of such inhibition of the other genes can be performed as described herein.


[0054] Other features and advantages of the invention will be apparent from the following description of the preferred embodiments thereof, and from the claims.







DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0055] First the drawings will be described briefly.


[0056] Drawings


[0057]
FIG. 1 shows examples of chemically stabilized ribozyme motifs. HH Rz, 5 represents hammerhead ribozyme motif (Usman et al., 1996, Curr. Op. Struct. Bio., 1, 527); NCH Rz represents the NCH ribozyme motif (Ludwig & Sproat, International PCT Publication No. WO 98/58058); G-Cleaver, represents G-cleaver ribozyme motif (Kore et al., 1998, Nucleic Acids Research 26, 4116-4120). N or n, represent independently a nucleotide which may be same or different and have complementarity to each other; rI, represents ribo-Inosine nucleotide; arrow indicates the site of cleavage within the target. Position 4 of the HH Rz and the NCH Rz is shown as having 2′-C-allyl modification, but those skilled in the art will recognize that this position can be modified with other modifications well known in the art, so long as such modifications do not significantly inhibit the activity of the ribozyme.


[0058]
FIG. 2 shows an example of the Amberzyme ribozyme motif that is chemically stabilized (see, for example, Beigelman et al., International PCT publication No. WO 99/55857, incorporated by reference herein; also referred to as Class I Motif). The Amberzyme motif is a class of enzymatic nucleic molecules that do not require the presence of a ribonucleotide (2′-OH) group for its activity.


[0059]
FIG. 3 shows an example of the Zinzyme A ribozyme motif that is chemically stabilized (Beigelman et al., International PCT publication No. WO 99/55857, incorporated by reference herein; also referred to as Class A or Class II Motif). The Zinzyme motif is a class of enzymatic nucleic molecules that do not require the presence of a ribonucleotide (2′-OH) group for its activity.


[0060]
FIG. 4 shows an example of a DNAzyme motif described by Santoro et al., 1997, PNAS, 94, 4262.


[0061]
FIGS. 5A and 5B are diagrammatic schemes representative of the process used for Target Discovery in the instant invention. The process for Target Discovery is described in Jarvis et al., International PCT publication No. WO 98/50530, incorporated by reference herein in its entirety including the Figures.







MECHANISM OF ACTION OF NUCLEIC ACID MOLECULES OF THE INVENTION

[0062] Antisense:


[0063] Antisense molecules may be modified or unmodified RNA, DNA, or mixed polymer oligonucleotides which primarily function by specifically binding to matching sequences resulting in inhibition of peptide synthesis (Wu-Pong, Nov 1994, BioPharm, 20-33). The antisense oligonucleotide binds to target RNA by Watson Crick base-pairing and blocks gene expression by preventing ribosomal translation of the bound sequences either by steric blocking or by activating RNase H enzyme. Antisense molecules can also alter protein synthesis by interfering with RNA processing or transport from the nucleus into the cytoplasm (Mukhopadhyay & Roth, 1996, Crit. Rev. in Oncogenesis 7, 151-190).


[0064] In addition, binding of single stranded DNA to RNA may result in nuclease degradation of the heteroduplex (Wu-Pong, supra; Crooke, supra). To date, the only backbone modified DNA chemistry which will act as substrates for RNase H are phosphorothioates, phosphorodithioates, and borontrifluoridates. Recently it has been reported that 2′-arabino and 2′-fluoro arabino-containing oligos can also activate RNase H activity.


[0065] A number of antisense molecules have been described that utilize novel configurations of chemically modified nucleotides, secondary structure, and/or RNase H substrate domains (Woolf et al., International PCT Publication No. WO 98/13526; Thompson et al., International PCT Publication No. WO 99/54459; Hartmann et al., U.S. Ser. No. 60/101,174 which was filed on September 21, 1998) all of these are incorporated by reference herein in their entirety.


[0066] In addition, antisense deoxyoligoribonucleotides can be used to target RNA by means of DNA-RNA interactions, thereby activating RNase H, which digests the target RNA in the duplex. Antisense DNA can be expressed endogenously in vivo via the use of a single stranded DNA intracellular expression vector or equivalents and variations thereof.


[0067] Triplex Forming Oligonucleotides (TFO):


[0068] Single stranded DNA may be designed to bind to genomic DNA in a sequence specific manner. TFOs are comprised of pyrimidine-rich oligonucleotides which bind DNA helices through Hoogsteen Base-pairing (Wu-Pong, supra). The resulting triple helix composed of the DNA sense, DNA antisense, and TFO disrupts RNA synthesis by RNA polymerase. The TFO mechanism may result in gene expression or cell death since binding may be irreversible (Mukhopadhyay & Roth, supra).


[0069] 2-5A Antisense Chimera:


[0070] The 2-5A system is an interferon mediated mechanism for RNA degradation found in higher vertebrates (Mitra et al., 1996, Proc Nat Acad Sci USA 93, 6780-6785). Two types of enzymes, 2-5A synthetase and RNase L, are required for RNA cleavage. The 2-SA synthetases require double stranded RNA to form 2′-5′ oligoadenylates (2-SA). 2-5A then acts as an allosteric effector for utilizing RNase L which has the ability to cleave single stranded RNA. The ability to form 2-5A structures with double stranded RNA makes this system particularly useful for inhibition of viral replication.


[0071] (2′-5′) oligoadenylate structures may be covalently linked to antisense molecules to form chimeric oligonucleotides capable of RNA cleavage (Torrence, supra). These molecules putatively bind and activate a 2-SA dependent RNase, the oligonucleotide/enzyme complex then binds to a target RNA molecule which can then be cleaved by the RNase enzyme.


[0072] Enzymatic Nucleic Acid:


[0073] Seven basic varieties of naturally occurring enzymatic RNAs are presently known. In addition, several in vitro selection (evolution) strategies (Orgel, 1979, Proc. R. Soc. London, B 205, 435) have been used to evolve new nucleic acid catalysts capable of catalyzing cleavage and ligation of phosphodiester linkages (Joyce, 1989, Gene, 82, 83-87; Beaudry et al., 1992, Science 257, 635-641; Joyce, 1992, Scientific American 267, 90-97; Breaker et al., 1994, TIBTECH 12, 268; Bartel et al., 1993, Science 261:1411-1418; Szostak, 1993, TIBS 17, 89-93; Kumar et al., 1995, FASEB J., 9, 1183; Breaker, 1996, Curr. Op. Biotech., 7, 442; Santoro et al., 1997, Proc. Natl. Acad. Sci., 94, 4262; Tang et al., 1997, RNA 3, 914; Nakamaye & Eckstein, 1994, supra; Long & Uhlenbeck, 1994, supra; Ishizaka et al., 1995, supra; Vaish et al., 1997, Biochemistry 36, 6495; all of these are incorporated by reference herein). Each can catalyze a series of reactions including the hydrolysis of phosphodiester bonds in trans (and thus can cleave other RNA molecules) under physiological conditions.


[0074] Nucleic acid molecules of this invention will block to some extent CLCA1 protein expression and can be used to treat disease or diagnose disease associated with the levels of CLCA1.


[0075] The enzymatic nature of a ribozyme has significant advantages, such as the concentration of ribozyme necessary to affect a therapeutic treatment is lower. This advantage reflects the ability of the ribozyme to act enzymatically. Thus, a single ribozyme molecule is able to cleave many molecules of target RNA. In addition, the ribozyme is a highly specific inhibitor, with the specificity of inhibition depending not only on the base-pairing mechanism of binding to the target RNA, but also on the mechanism of target RNA cleavage. Single mismatches, or base-substitutions, near the site of cleavage can be chosen to completely eliminate catalytic activity of a ribozyme.


[0076] Nucleic acid molecules having an endonuclease enzymatic activity are able to repeatedly cleave other separate RNA molecules in a nucleotide base sequence-specific manner. Such enzymatic nucleic acid molecules can be targeted to virtually any RNA transcript, and achieve efficient cleavage in vitro (Zaug et al., 324, Nature 429 1986 ; Uhlenbeck, 1987 Nature 328, 596; Kim et al., 84 Proc. Natl. Acad. Sci. USA 8788, 1987; Dreyfus, 1988, Einstein Quart. J Bio. Med., 6, 92; Haseloff and Gerlach, 334 Nature 585, 1988; Cech, 260 JAMA 3030, 1988; and Jefferies et al., 17 Nucleic Acids Research 1371, 1989; Santoro et al., 1997 supra).


[0077] Because of their sequence specificity, trans-cleaving ribozymes show promise as therapeutic agents for human disease (Usman and McSwiggen, 1995 Ann. Rep. Med. Chem. 30, 285-294; Christoffersen and Marr, 1995 J. Med. Chem. 38, 2023-2037). Ribozymes can be designed to cleave specific RNA targets within the background of cellular RNA. Such a cleavage event renders the RNA non-functional and abrogates protein expression from that RNA. In this manner, synthesis of a protein associated with a disease state can be selectively inhibited (Warashina et al., 1999, Chemistry and Biology, 6, 237-250).


[0078] The nucleic acid molecules of the instant invention are also referred to as GeneBloc reagents, which are essentially nucleic acid molecules (e.g.; ribozymes, antisense) capable of down-regulating gene expression.


[0079] GeneBlocs are modified oligonucleotides including ribozymes and modified antisense oligonucleotides that bind to and target specific mRNA molecules. Because GeneBlocs can be designed to target any specific mRNA, their potential applications are quite broad. Traditional antisense approaches have often relied heavily on the use of phosphorothioate modifications to enhance stability in biological samples, leading to a myriad of specificity problems stemming from non-specific protein binding and general cytotoxicity (Stein, 1995, Nature Medicine, 1, 1119). In contrast, GeneBlocs contain a number of modifications that confer nuclease resistance while making minimal use of phosphorothioate linkages, which reduces toxicity, increases binding affinity and minimizes non-specific effects compared with traditional antisense oligonucleotides. Similar reagents have recently been utilized successfully in various cell culture systems (Vassar, et al., 1999, Science, 286, 735) and in vivo (Jarvis et al., manuscript in preparation). In addition, novel cationic lipids can be utilized to enhance cellular uptake in the presence of serum. Since ribozymes and antisense oligonucleotides regulate gene expression at the RNA level, the ability to maintain a steady-state dose of GeneBloc over several days was important for target protein and phenotypic analysis. The advances in resistance to nuclease degradation and prolonged activity in vitro have supported the use of GeneBlocs in target validation applications.


[0080] Target Sites


[0081] Targets for useful ribozymes and antisense nucleic acids can be determined as disclosed in Draper et al, WO 93/23569; Sullivan et al., WO 93/23057; Thompson et al., WO 94/02595; Draper et al., WO 95/04818; McSwiggen et al., U.S. Pat. No. 5,525,468. All of these publications are hereby incorporated by reference herein in their totality. Other examples include the following PCT applications, which concern inactivation of expression of disease-related genes: WO 95/23225, WO 95/13380, WO 94/02595, all of which are incorporated by reference herein. Rather than repeat the guidance provided in those documents here, specific examples of such methods are provided herein, not limiting to those in the art. Ribozymes and antisense to such targets are designed as described in those applications and synthesized to be tested in vitro and in vivo, as also described. The sequences of human CLCA1 RNAs were screened for optimal enzymatic nucleic acid and antisense target sites using a computer-folding algorithm. Antisense, hammerhead, DNAzyme, NCH, amberzyme, zinzyme, or G-Cleaver ribozyme binding/cleavage sites were identified. These sites are shown in Tables III to IX (all sequences are 5′ to 3′ in the tables; the underlined region can be any base-paired sequence, the actual sequence is not relevant here). The nucleotide base position is noted in the Tables as that site to be cleaved by the designated type of enzymatic nucleic acid molecule. While human sequences can be screened and enzymatic nucleic acid molecule and/or antisense thereafter designed, as discussed in Stinchcomb et al., WO 95/23225, mouse targeted ribozymes may be useful to test efficacy of action of the enzymatic nucleic acid molecule and/or antisense prior to testing in humans.


[0082] Antisense, hammerhead, DNAzyme, NCH, amberzyme, zinzymne or G-Cleaver ribozyme binding/cleavage sites were identified. The nucleic acid molecules are individually analyzed by computer folding (Jaeger et al., 1989 Proc. Natl. Acad. Sci. USA, 86, 7706) to assess whether the sequences fold into the appropriate secondary structure. Those nucleic acid molecules with unfavorable intramolecular interactions such as between the binding arms and the catalytic core are eliminated from consideration. Varying binding arm lengths can be chosen to optimize activity.


[0083] Antisense, hammerhead, DNAzyme, NCH, amberzyme, zinzyme or G-Cleaver ribozyme binding/cleavage sites were identified and were designed to anneal to various sites in the RNA target. The binding arms are complementary to the target site sequences described above. The nucleic acid molecules were chemically synthesized. The method of synthesis used follows the procedure for normal DNA/RNA synthesis as described below and in Usman et al., 1987 J. Am. Chem. Soc., 109, 7845; Scaringe et al., 1990 Nucleic Acids Res., 18, 5433; Wincott et al., 1995 Nucleic Acids Res. 23, 2677-2684; and Caruthers et al., 1992, Methods in Enzymology 211,3-19.


[0084] Synthesis of Nucleic Acid Molecules


[0085] Synthesis of nucleic acids greater than 100 nucleotides in length is difficult using automated methods, and the therapeutic cost of such molecules is prohibitive. In this invention, small nucleic acid motifs (“small refers to nucleic acid motifs no more than 100 nucleotides in length, preferably no more than 80 nucleotides in length, and most preferably no more than 50 nucleotides in length; e.g., antisense oligonucleotides, hammerhead or the NCH ribozymes) are preferably used for exogenous delivery. The simple structure of these molecules increases the ability of the nucleic acid to invade targeted regions of RNA structure. Exemplary molecules of the instant invention are chemically synthesized, and others can similarly be synthesized.


[0086] Oligonucleotides (e.g.; antisense GeneBlocs) are synthesized using protocols known in the art as described in Caruthers et al., 1992, Methods in Enzymology 211, 3-19, Thompson et al., International PCT Publication No. WO 99/54459, Wincott et al., 1995, Nucleic Acids Res. 23, 2677-2684, Wincott et al., 1997, Methods Mol. Bio., 74, 59, Brennan et al., 1998, Biotechnol Bioeng., 61, 33-45, and Brennan, US patent No. 6,001,311. All of these references are incorporated herein by reference. The synthesis of oligonucleotides makes use of common nucleic acid protecting and coupling groups, such as dimethoxytrityl at the 5′-end, and phosphoramidites at the 3′-end. In a non-limiting example, small scale syntheses are conducted on a 394 Applied Biosystems, Inc. synthesizer using a 0.2 Rmol scale protocol with a 2.5 min coupling step for 2′-O-methylated nucleotides and a 45 sec coupling step for 2′-deoxy nucleotides. Table II outlines the amounts and the contact times of the reagents used in the synthesis cycle. Alternatively, syntheses at the 0.2 μmol scale can be performed on a 96-well plate synthesizer, such as the instrument produced by Protogene (Palo Alto, Calif.) with minimal modification to the cycle. A 33-fold excess (60 μL of 0.11 M=6.6 Rmol) of 2′-O-methyl phosphoramidite and a 105-fold excess of S-ethyl tetrazole (60 μL of 0.25 M =15 μmol) can be used in each coupling cycle of 2′-O-methyl residues relative to polymer-bound 5′-hydroxyl. A 22-fold excess (40 μL of 0.11 M=4.4 μmol) of deoxy phosphoramidite and a 70-fold excess of S-ethyl tetrazole (40 μL of 0.25 M =10 μmol) can be used in each coupling cycle of deoxy residues relative to polymer-bound 5′-hydroxyl. Average coupling yields on the 394 Applied Biosystems, Inc. synthesizer, determined by colorimetric quantitation of the trityl fractions, are typically 97.5-99%. Other oligonucleotide synthesis reagents for the 394 Applied Biosystems, Inc. synthesizer include; detritylation solution is 3% TCA in methylene chloride (ABI); capping is performed with 16% N-methyl imidazole in THF (ABI) and 10% acetic anhydride/10% 2,6-lutidine in THF (ABI); and oxidation solution is 16.9 mM 12, 49 mM pyridine, 9% water in THF (PERSEPTIVE™). Burdick & Jackson Synthesis Grade acetonitrile is used directly from the reagent bottle. S-Ethyltetrazole solution (0.25 M in acetonitrile) is made up from the solid obtained from American International Chemical, Inc. Alternately, for the introduction of phosphorothioate linkages, Beaucage reagent (3H-1,2-Benzodithiol-3-one 1,1-dioxide, 0.05 M in acetonitrile) is used.


[0087] Deprotection of the antisense oligonucleotides is performed as follows: the polymer-bound trityl-on oligoribonucleotide is transferred to a 4 mL glass screw top vial and suspended in a solution of 40% aq. methylamine (1 mL) at 65° C. for 10 min. After cooling to -20° C., the supernatant is removed from the polymer support.


[0088] The support is washed three times with 1.0 mL of EtOH:MeCN:H20/3 :1: 1, vortexed and the supernatant is then added to the first supernatant. The combined supernatants, containing the oligoribonucleotide, are dried to a white powder. The method of synthesis used for normal RNA including certain enzymatic nucleic acid molecules follows the procedure as described in Usman et al., 1987, J. Am. Chem. Soc., 109, 7845; Scaringe et al., 1990, Nucleic Acids Res., 18, 5433; Wincott et al., 1995, Nucleic Acids Res. 23, 2677-2684 and Wincott et al., 1997, Methods Mol. Bio., 74, 59, and makes use of common nucleic acid protecting and coupling groups, such as dimethoxytrityl at the 5′-end, and phosphoramidites at the 3′-end. In a non-limiting example, small scale syntheses are conducted on a 394 Applied Biosystems, Inc. synthesizer using a 0.2 μmol scale protocol with a 7.5 min coupling step for alkylsilyl protected nucleotides and a 2.5 min coupling step for 2′-O-methylated nucleotides. Table II outlines the amounts and the contact times of the reagents used in the synthesis cycle. Alternatively, syntheses at the 0.2 μmol scale can be done on a 96-well plate synthesizer, such as the instrument produced by Protogene (Palo Alto, Calif.) with minimal modification to the cycle. A 33-fold excess (60 μL of 0.11 M=6.6 lmol) of 2′-O-methyl phosphoramidite and a 75-fold excess of S-ethyl tetrazole (60 μL of 0.25 M =15 μmol) can be used in each coupling cycle of 2′-O-methyl residues relative to polymer-bound 5′-hydroxyl. A 66-fold excess (120 μL of 0.11 M =13.2 μmol) of alkylsilyl (ribo) protected phosphoramidite and a 150-fold excess of S-ethyl tetrazole (120 μL of 0.25 M =30 gmol) can be used in each coupling cycle of ribo residues relative to polymer-bound 5′-hydroxyl. Average coupling yields on the 394 Applied Biosystems, Inc. synthesizer, determined by colorimetric quantitation of the trityl fractions, are typically 97.5-99%. Other oligonucleotide synthesis reagents for the 394 Applied Biosystems, Inc. 10 synthesizer include; detritylation solution is 3% TCA in methylene chloride (ABI);


[0089] capping is performed with 16% N-methyl imidazole in THF (ABI) and 10% acetic anhydride/10% 2,6-lutidine in THF (ABI); oxidation solution is 16.9 mM 12, 49 mM pyridine, 9% water in THF (PERSEPTIVET). Burdick & Jackson Synthesis Grade acetonitrile is used directly from the reagent bottle. S-Ethyltetrazole solution (0.25 M in acetonitrile) is made up from the solid obtained from American International Chemical, Inc. Alternately, for the introduction of phosphorothioate linkages, Beaucage reagent (3H-1,2-Benzodithiol-3-one 1,1-dioxide 0.05 M in acetonitrile) is used.


[0090] Deprotection of the RNA is performed using either a two-pot or one-pot protocol. For the two-pot protocol, the polymer-bound trityl-on oligoribonucleotide is transferred to a 4 mL glass screw top vial and suspended in a solution of 40% aq. methylamine (1 mL) at 65° C. for 10 min. After cooling to -20° C., the supernatant is removed from the polymer support. The support is washed three times with 1.0 mL of EtOH:MeCN:H20/3:1:1, vortexed and the supernatant is then added to the first supernatant. The combined supernatants, containing the oligoribonucleotide, are dried to a white powder. The base deprotected oligoribonucleotide is resuspended in anhydrous TEA/HF/NMP solution (300 μL of a solution of 1.5 mL N-methylpyrrolidinone, 750 μL TEA and 1 mL TEA.3HF to provide a 1.4 M HF concentration) and heated to 65° C. After 1.5 h, the oligomer is quenched with 1.5 M NH4HCO3.


[0091] Alternatively, for the one-pot protocol, the polymer-bound trityl-on oligoribonucleotide is transferred to a 4 mL glass screw top vial and suspended in a solution of 33% ethanolic methylamine/DMSO: 1/1 (0.8 mL) at 65° C. for 15 min.


[0092] The vial is brought to r.t. TEA3HF (0.1 mL) is added and the vial is heated at 65° C. for 15 min. The sample is cooled at −20° C. and then quenched with 1.5 M NH4HCO3.


[0093] For purification of the trityl-on oligomers, the quenched NH4HCO3 solution is loaded onto a C-18 containing cartridge that had been prewashed with acetonitrile followed by 50 mM TEAA. After washing the loaded cartridge with water, the RNA is detritylated with 0.5% TFA for 13 min. The cartridge is then washed again with water, salt exchanged with 1 M NaCl and washed with water again. The oligonucleotide is then eluted with 30% acetonitrile.


[0094] Inactive hammerhead ribozymes or binding attenuated control (BAC) oligonucleotides) are synthesized by substituting a U for G5 and a U for A14 (numbering from Hertel, K. J., et al., 1992, Nucleic Acids Res., 20, 3252). Similarly, one or more nucleotide substitutions can be introduced in other enzymatic nucleic acid molecules to inactivate the molecule and such molecules can serve as a negative control.


[0095] The average stepwise coupling yields are typically >98% (Wincott et al., 1995 Nucleic Acids Res. 23, 2677-2684). Those of ordinary skill in the art will recognize that the scale of synthesis can be adapted to be larger or smaller than the examples described above including but not limited to 96-well format, all that is important is the ratio of chemicals used in the reaction.


[0096] Alternatively, the nucleic acid molecules of the present invention can be synthesized separately and joined together post-synthetically, for example by ligation (Moore et al., 1992, Science 256, 9923; Draper et al., International PCT publication No. WO 93/23569; Shabarova et al., 1991, Nucleic Acids Research 19, 4247; Bellon et al., 1997, Nucleosides & Nucleotides, 16, 951; Bellon et al., 1997, Bioconjugate Chem. 8, 204).


[0097] The nucleic acid molecules of the present invention are modified extensively to enhance stability by modification with nuclease resistant groups, for example, 2′-amino, 2′-C-allyl, 2′-flouro, 2′-O-methyl, 2′-H (for a review see Usman and Cedergren, 1992, TIBS 17, 34; Usman et al., 1994, Nucleic Acids Symp. Ser. 31, 163). Ribozymes are purified by gel electrophoresis using general methods or are purified by high pressure liquid chromatography (HPLC; See Wincott et al., supra, the totality of which is hereby incorporated herein by reference) and are re-suspended in water.


[0098] The sequences of the ribozymes and antisense constructs that are chemically synthesized, useful in this study, are shown in Tables III to IX. Those in the art will recognize that these sequences are representative only of many more such sequences where the enzymatic portion of the ribozyme (all but the binding arms) is altered to affect activity. The ribozyme and antisense construct sequences listed in Tables III to IX may be formed of ribonucleotides or other nucleotides or non-nucleotides. Such ribozymes with enzymatic activity are equivalent to the ribozymes described specifically in the Tables.


[0099] Optimizing Activity of the Nucleic Acid Molecule of the Invention.


[0100] Chemically synthesizing nucleic acid molecules with modifications (base, sugar and/or phosphate) that prevent their degradation by serum ribonucleases may increase their potency (see e.g., Eckstein et al., International Publication No.


[0101] WO 92/07065; Perrault et al., 1990 Nature 344, 565; Pieken et al., 1991, Science 253, 314; Usman and Cedergren, 1992, Trends in Biochem. Sci. 17, 334; Usman et al., International Publication No. WO 93/15187; Rossi et al., International Publication No. WO 91/03162; Sproat, U.S. Pat. No. 5,334,711; and Burgin et al., supra; all of these describe various chemical modifications that can be made to the base, phosphate and/or sugar moieties of the nucleic acid molecules described herein. All these references are incorporated by reference herein. Modifications which enhance their efficacy in cells, and removal of bases from nucleic acid molecules to shorten oligonucleotide synthesis times and reduce chemical requirements are desired.


[0102] There are several examples in the art describing sugar, base and phosphate modifications that can be introduced into nucleic acid molecules with significant enhancement in their nuclease stability and efficacy. For example, oligonucleotides are modified to enhance stability and/or enhance biological activity by modification with nuclease resistant groups, for example, 2′-amino, 2′-C-allyl, 2′-flouro, 2′-O-methyl, 2′-H, nucleotide base modifications (for a review see Usman and Cedergren, 1992, TIBS. 17, 34; Usman et al., 1994, Nucleic Acids Symp. Ser. 31, 163; Burgin et al., 1996, Biochemistry, 35, 14090). Sugar modifications of nucleic acid molecules have been extensively described in the art (see Eckstein et al., International Publication PCT No. WO 92/07065; Perrault et al. Nature, 1990, 344, 565-568; Pieken et al. Science, 1991, 253, 314-317; Usman and Cedergren, Trends in Biochem. Sci. , 1992, 17, 334-339; Usman et al. International Publication PCT No. WO 93/15187; Sproat, U.S. Pat. No. 5,334,711 and Beigelman et al., 1995, J. Biol. Chem., 270, 25702; Beigelman et al., International PCT publication No. WO 97/26270; Beigelman et al., U.S. Pat. No. 5,716,824; Usman et al., U.S. Pat. No. 5,627,053; Woolf et al., International PCT Publication No. WO 98/13526; 35 Thompson et al., U.S. Ser. No. 60/082,404 which was filed on Apr. 20, 1998; Karpeisky et al., 1998, Tetrahedron Lett., 39, 1131; Earnshaw and Gait, 1998, Biopolymers (Nucleic acid Sciences), 48, 39-55; Verma and Eckstein, 1998, Annu. Rev. Biochem., 67, 99-134; and Burlina et al., 1997, Bioorg. Med. Chem., 5, 1999-2010; all of the references are hereby incorporated by reference herein in their totalities). Such publications describe general methods and strategies to determine the location of incorporation of sugar, base and/or phosphate modifications and the like into ribozymes without inhibiting catalysis. In view of such teachings, similar modifications can be used as described herein to modify the nucleic acid molecules of the instant invention.


[0103] While chemical modification of oligonucleotide internucleotide linkages with phosphorothioate, phosphorothioate, and/or 5′-methylphosphonate linkages improves stability, too many of these modifications may cause some toxicity. Therefore when designing nucleic acid molecules the amount of these internucleotide linkages should be minimized. The reduction in the concentration of these linkages should lower toxicity resulting in increased efficacy and higher specificity of these molecules.


[0104] Nucleic acid molecules having chemical modifications which maintain or enhance activity are provided. Such nucleic acid is also generally more resistant to nucleases than unmodified nucleic acid. Thus, in a cell and/or in vivo the activity may not be significantly lowered. Therapeutic nucleic acid molecules delivered exogenously must optimally be stable within cells until translation of the target RNA has been inhibited long enough to reduce the levels of the undesirable protein. This period of time varies between hours to days depending upon the disease state. Clearly, nucleic acid molecules must be resistant to nucleases in order to function as effective intracellular therapeutic agents. Improvements in the chemical synthesis of RNA and DNA (Wincott et al., 1995 Nucleic Acids Res. 23, 2677; Caruthers et al., 1992, Methods in Enzymology 211,3-19 (incorporated by reference herein) have expanded the ability to modify nucleic acid molecules by introducing nucleotide modifications to enhance their nuclease stability as described above.


[0105] Use of these the nucleic acid-based molecules of the invention will lead to better treatment of the disease progression by affording the possibility of combination therapies (e.g., multiple antisense or enzymatic nucleic acid molecules targeted to different genes, nucleic acid molecules coupled with known small molecule inhibitors, or intermittent treatment with combinations of molecules (including different motifs) and/or other chemical or biological molecules). The treatment of patients with nucleic acid molecules may also include combinations of different types of nucleic acid molecules.


[0106] Therapeutic nucleic acid molecules (e.g., enzymatic nucleic acid molecules and antisense nucleic acid molecules) delivered exogenously must optimally be stable within cells until translation of the target RNA has been inhibited long enough to reduce the levels of the undesirable protein. This period of time varies between hours to days depending upon the disease state. Clearly, these nucleic acid molecules must be resistant to nucleases in order to function as effective intracellular therapeutic agents. Improvements in the chemical synthesis of nucleic acid molecules described in the instant invention and in the art have expanded the ability to modify nucleic acid molecules by introducing nucleotide modifications to enhance their nuclease stability as described above.


[0107] By “enhanced enzymatic activity” is meant to include activity measured in cells and/or in vivo where the activity is a reflection of both catalytic activity and ribozyme stability. In this invention, the product of these properties is increased or not significantly (less than 10-fold) decreased in vivo compared to an all RNA ribozyme or all DNA enzyme.


[0108] In yet another preferred embodiment, nucleic acid catalysts having chemical modifications which maintain or enhance enzymatic activity are provided. Such nucleic acid is also generally more resistant to nucleases than unmodified nucleic acid. Thus, in a cell and/or in vivo the activity may not be significantly lowered. As exemplified herein such ribozymes are useful in a cell and/or in vivo even if activity over all is reduced 10 fold (Burgin et al., 1996, Biochemistry, 35, 14090). Such ribozymes herein are said to “maintain” the enzymatic activity of an all RNA ribozyme.


[0109] In another aspect the nucleic acid molecules comprise a 5′ and/or a 3′-cap structure.


[0110] By “cap structure” is meant chemical modifications, which have been incorporated at either terminus of the oligonucleotide (see, for example, Wincott et al., WO 97/26270, incorporated by reference herein). These terminal modifications protect the nucleic acid molecule from exonuclease degradation, and may help in delivery and/or localization within a cell. The cap may be present at the 5′-terminus (5′-cap) or at the 3′-terminus (3′-cap) or may be present on both termini. In non-limiting examples the 5′-cap is selected from the group comprising inverted abasic residue (moiety), 4′,5′-methylene nucleotide; 1-(beta-D-erythrofuranosyl) nucleotide, 4′-thio nucleotide, carbocyclic nucleotide; 1,5-anhydrohexitol nucleotide; L-nucleotides; alpha-nucleotides; modified base nucleotide; phosphorodithioate linkage; threo-pentofuranosyl nucleotide; acyclic 3′,4′-seco nucleotide; acyclic 3,4-dihydroxybutyl nucleotide; acyclic 3,5-dihydroxypentyl nucleotide, 3′-3′-inverted nucleotide moiety; 3′-3′-inverted abasic moiety; 3′-2′-inverted nucleotide moiety; 3′-2′-inverted abasic moiety; 1,4-butanediol phosphate; 3′-phosphoramidate; hexylphosphate; aminohexyl phosphate; 3′-phosphate; 3′-phosphorothioate; phosphorodithioate; or bridging or non-bridging methylphosphonate moiety (for more details see Wincott et al., International PCT publication No. WO 97/26270, incorporated by reference herein).


[0111] In yet another preferred embodiment, the 3′-cap is selected from a group comprising, 4′,5′-methylene nucleotide; 1-(beta-D-erythrofuranosyl) nucleotide; 4′-thio nucleotide, carbocyclic nucleotide; 5′-amino-alkyl phosphate; 1,3-diamino-2-propyl phosphate, 3-aminopropyl phosphate; 6-aminohexyl phosphate; 1,2-aminododecyl phosphate; hydroxypropyl phosphate; 1,5-anhydrohexitol nucleotide; L-nucleotide; alpha-nucleotide; modified base nucleotide; phosphorodithioate; threo-pentofuranosyl nucleotide; acyclic 3′,4′-seco nucleotide; 3,4-dihydroxybutyl nucleotide; 3,5-dihydroxypentyl nucleotide, 5′-5′-inverted nucleotide moiety; 5′-5′-inverted abasic moiety; 5′-phosphoramidate; 5′-phosphorothioate; 1,4-butanediol phosphate; 5′-amino; bridging and/or non-bridging 5′-phosphoramidate, phosphorothioate and/or phosphorodithioate, bridging or non bridging methylphosphonate and 5′-mercapto moieties (for more details, see Beaucage and Iyer, 1993, Tetrahedron 49, 1925; incorporated by reference herein).


[0112] By the term “non-nucleotide” is meant any group or compound which can be incorporated into a nucleic acid chain in the place of one or more nucleotide units, including either sugar and/or phosphate substitutions, and allows the remaining bases to exhibit their enzymatic activity. The group or compound is abasic in that it does not contain a commonly recognized nucleotide base, such as adenosine, guanine, cytosine, uracil or thymine.


[0113] An “alkyl” group refers to a saturated aliphatic hydrocarbon, including straight-chain, branched-chain, and cyclic alkyl groups. Preferably, the alkyl group has 1 to 12 carbons. More preferably it is a lower alkyl of from 1 to 7 carbons, more preferably 1 to 4 carbons. The alkyl group may be substituted or unsubstituted. When substituted the substituted group(s) is preferably, hydroxyl, cyano, alkoxy, ═O, ═S, NO2 or N(CH3)2, amino, or SH. The term also includes alkenyl groups which are unsaturated hydrocarbon groups containing at least one carbon-carbon double bond, including straight-chain, branched-chain, and cyclic groups. Preferably, the alkenyl group has 1 to 12 carbons. More preferably it is a lower alkenyl of from 1 to 7 carbons, more preferably 1 to 4 carbons. The alkenyl group may be substituted or unsubstituted. When substituted the substituted group(s) is preferably, hydroxyl, cyano, alkoxy, ═O, ═S, NO2, halogen, N(CH3)2, amino, or SH. The term “alkyl” also includes alkynyl groups which have an unsaturated hydrocarbon group containing at least one carbon-carbon triple bond, including straight-chain, branched-chain, and cyclic groups. Preferably, the alkynyl group has 1 to 12 carbons. More preferably it is a lower alkynyl of from 1 to 7 carbons, more preferably 1 to 4 carbons. The alkynyl group may be substituted or unsubstituted. When substituted the substituted group(s) is preferably, hydroxyl, cyano, alkoxy, ═O, ═S, NO2 or N(CH3)2, amino or SH.


[0114] Such alkyl groups may also include aryl, alkylaryl, carbocyclic aryl, heterocyclic aryl, amide and ester groups. An “aryl” group refers to an aromatic group which has at least one ring having a conjugated π electron system and includes carbocyclic aryl, heterocyclic aryl and biaryl groups, all of which may be optionally substituted. The preferred substituent(s) of aryl groups are halogen, trihalomethyl, hydroxyl, SH, OH, cyano, alkoxy, alkyl, alkenyl, alkynyl, and amino groups. An “alkylaryl” group refers to an alkyl group (as described above) covalently joined to an aryl group (as described above). Carbocyclic aryl groups are groups wherein the ring atoms on the aromatic ring are all carbon atoms. The carbon atoms are optionally substituted. Heterocyclic aryl groups are groups having from 1 to 3 heteroatoms as ring atoms in the aromatic ring and the remainder of the ring atoms are carbon atoms. Suitable heteroatoms include oxygen, sulfur, and nitrogen, and include furanyl, thienyl, pyridyl, pyrrolyl, N-lower alkyl pyrrolo, pyrimidyl, pyrazinyl, imidazolyl and the like, all optionally substituted. An “amide” refers to an —C(O)—NH—R, where R is either alkyl, aryl, alkylaryl or hydrogen. An “ester” refers to an —C(O)—OR′, where R is either alkyl, aryl, alkylaryl or hydrogen.


[0115] By “nucleotide” as used herein is as recognized in the art to include natural bases (standard), and modified bases well known in the art. Such bases are generally located at the 1′ position of a nucleotide sugar moiety. Nucleotides generally comprise a base, sugar and a phosphate group. The nucleotides can be unmodified or modified at the sugar, phosphate and/or base moiety, (also referred to interchangeably as nucleotide analogs, modified nucleotides, non-natural nucleotides, non-standard nucleotides and other; see for example, Usman and McSwiggen, supra; Eckstein et al., International PCT Publication No. WO 92/07065; Usman et al., International PCT Publication No. WO 93/15187; Uhlmann & Peyman, 1990, Chemical Reviews, 90, 4, 544-579, all are hereby incorporated by reference herein). There are several examples of modified nucleic acid bases known in the art as summarized by Limbach et al., 1994, Nucleic Acids Res. 22, 2183. Some of the non-limiting examples of base modifications that can be introduced into nucleic acid molecules include, inosine, purine, pyridin-4-one, pyridin-2-one, phenyl, pseudouracil, 2,4,6-trimethoxy benzene, 3-methyl uracil, dihydrouridine, naphthyl, aminophenyl, 5-alkylcytidines (e.g., 5-methylcytidine), 5-alkyluridines (e.g., ribothymidine), 5-halouridine (e.g., 5-bromouridine) or 6-azapyrimidines or 6-alkylpyrimidines (e.g. 6-methyluridine), propyne, and others (Burgin et al., 1996, Biochemistry, 35, 14090; Uhlman & Peyman, supra). By “modified bases” in this aspect is meant nucleotide bases other than adenine, guanine, cytosine and uracil at 1′ position or their equivalents; such bases may be used at any position, for example, within the catalytic core of an enzymatic nucleic acid molecule and/or in the substrate-binding regions of the nucleic acid molecule.


[0116] In a preferred embodiment, the invention features modified ribozymes with phosphate backbone modifications comprising one or more phosphorothioate, phosphorodithioate, methylphosphonate, morpholino, amidate carbamate, carboxymethyl, acetamidate, polyamide, sulfonate, sulfonamide, sulfamate, fornacetal, thioformacetal, and/or alkylsilyl, substitutions. For a review of oligonucleotide backbone modifications see Hunziker and Leumann, 1995, Nucleic Acid Analogues: Synthesis and Properties, in Modern Synthetic Methods, VCH, 331-417, and Mesmaeker et al., 1994, Novel Backbone Replacements for Oligonucleotides, in Carbohydrate Modifications in Antisense Research, ACS, 24-39. These references are hereby incorporated by reference herein.


[0117] By “abasic” is meant sugar moieties lacking a base or having other chemical groups in place of a base at the 1′ position, (for more details, see Wincott et al., International PCT publication No. WO 97/26270).


[0118] By “unmodified nucleoside” is meant one of the bases adenine, cytosine, guanine, thymine, uracil joined to the 1′ carbon of P-D-ribo-furanose.


[0119] By “modified nucleoside” is meant any nucleotide base which contains a modification in the chemical structure of an unmodified nucleotide base, sugar and/or phosphate.


[0120] In connection with 2′-modified nucleotides as described for the present invention, by “amino” is meant 2′-NH2 or 2′-O—NH2, which may be modified or unmodified. Such modified groups are described, for example, in Eckstein et al., U.S. Pat. No. 5,672,695 and Matulic-Adamic et al., WO 98/28317, respectively, which are both incorporated by reference herein in their entireties.


[0121] Various modifications to nucleic acid (e.g., antisense and ribozyme) structure can be made to enhance the utility of these molecules. Such modifications will enhance shelf-life, half-life in vitro, stability, and ease of introduction of such oligonucleotides to the target site, e.g., to enhance penetration of cellular membranes, and confer the ability to recognize and bind to targeted cells.


[0122] Use of these molecules will lead to better treatment of the disease progression by affording the possibility of combination therapies (e.g., multiple ribozymes targeted to different genes, ribozymes coupled with known small molecule inhibitors, or intermittent treatment with combinations of ribozymes (including different ribozyme motifs) and/or other chemical or biological molecules). The treatment of patients with nucleic acid molecules may also include combinations of different types of nucleic acid molecules. Therapies may be devised which include a mixture of ribozymes (including different ribozyme motifs), antisense and/or 2-5A chimera molecules to one or more targets to alleviate symptoms of a disease.


[0123] Administration of Nucleic Acid Molecules


[0124] Methods for the delivery of nucleic acid molecules are described in Akhtar et al., 1992, Trends Cell Bio., 2, 139; and Delivery Strategies for Antisense Oligonucleotide Therapeutics, ed. Akhtar, 1995 which are both incorporated herein by reference. Sullivan et al., PCT WO 94/02595, further describes the general methods for delivery of enzymatic RNA molecules. These protocols may be utilized for the delivery of virtually any nucleic acid molecule. Nucleic acid molecules may be administered to cells by a variety of methods known to those familiar to the art, including, but not restricted to, encapsulation in liposomes, by iontophoresis, or by incorporation into other vehicles, such as hydrogels, cyclodextrins, biodegradable nanocapsules, and bioadhesive microspheres. For some indications, nucleic acid molecules may be directly delivered ex vivo to cells or tissues with or without the aforementioned vehicles. Alternatively, the nucleic acid/vehicle combination is locally delivered by direct injection or by use of a catheter, infusion pump or stent. Other routes of delivery include, but are not limited to, intravascular, intramuscular, subcutaneous or joint injection, aerosol inhalation, oral (tablet or pill form), topical, systemic, ocular, intraperitoneal and/or intrathecal delivery. More detailed descriptions of nucleic acid delivery and administration are provided in Sullivan et al., supra, Draper et al, PCT WO93/23569, Beigelman et al., PCT W099/05094, and Klimuk et al., PCT WO99/04819 all of which have been incorporated by reference herein.


[0125] In addition, the nucleic acid molecules of the instant invention, used to treat pulmonary diseases and disorders, may be administered directly to the lungs via pulmonary delivery. The pulmonary delivery of oligonucleotides is described by Bennett et al., International PCT publication Nos. WO/9960166 and WO/9960010; Danahay et al., 1999, Pharm. Res., 16(10), 1542-1549; Metzger and Nyce, 1999, J. Allergy Clin. Immunol., 104(2, Pt. 1), 260-266; Nicklin et al., 1998, Pharm. Res., 15(4), 583-591; Illum and Watts, International PCT publication No. WO/9735562; and Nyce, 1997, Expert Opin. Invest. Drugs, 6(9), 1149-1156.


[0126] The molecules of the instant invention can be used as pharmaceutical agents. Pharmaceutical agents prevent, inhibit the occurrence, or treat (alleviate a symptom to some extent, preferably all of the symptoms) of a disease state in a patient.


[0127] The negatively charged polynucleotides of the invention can be administered (e.g., RNA, DNA or protein) and introduced into a patient by any standard means, with or without stabilizers, buffers, and the like, to form a pharmaceutical composition. When it is desired to use a liposome delivery mechanism, standard protocols for formation of liposomes can be followed. The compositions of the present invention may also be formulated and used as tablets, capsules or elixirs for oral administration; suppositories for rectal administration; sterile solutions; suspensions for injectable administration; and other compositions known in the art. The present invention also includes pharmaceutically acceptable formulations of the compounds described. These formulations include salts of the above compounds, e.g., acid addition salts, including salts of hydrochloric, hydrobromic, acetic acid, and benzene sulfonic acid.


[0128] A pharmacological composition or formulation refers to a composition or formulation in a form suitable for administration, e.g., systemic administration, into a cell or patient, preferably a human. Suitable forms, in part, depend upon the use or the route of entry, for example oral, transdermal, or by injection. Such forms should not prevent the composition or formulation from reaching a target cell (i.e., a cell to which the negatively charged polymer is desired to be delivered to). For example, pharmacological compositions injected into the blood stream should be soluble.


[0129] Other factors are known in the art, and include considerations such as toxicity and forms which prevent the composition or formulation from exerting its effect. By “systemic administration” is meant in vivo systemic absorption or accumulation of drugs in the blood stream followed by distribution throughout the entire body. Administration routes that lead to systemic absorption include, without limitations: intravenous, subcutaneous, intraperitoneal, inhalation, oral, intrapulmonary and intramuscular. Each of these administration routes exposes the desired negatively charged polymers, e.g., nucleic acids, to an accessible diseased tissue. The rate of entry of a drug into the circulation has been shown to be a function of molecular weight or size. The use of a liposome or other drug carrier comprising the compounds of the instant invention can potentially localize the drug, for example, in certain tissue types, such as the tissues of the reticular endothelial system (RES). A liposome formulation that can facilitate the association of drug with the surface of cells, such as, lymphocytes and macrophages is also useful. This approach may provide enhanced delivery of the drug to target cells by taking advantage of the specificity of macrophage and lymphocyte immune recognition of abnormal cells, such as cancer cells.


[0130] By pharmaceutically acceptable formulation is meant, a composition or formulation that allows for the effective distribution of the nucleic acid molecules of the instant invention in the physical location most suitable for their desired activity.


[0131] Non-limiting examples of agents suitable for formulation with the nucleic acid molecules of the instant invention include: P-glycoprotein inhibitors (such as Pluronic P85) which can enhance entry of drugs into the CNS (Jolliet-Riant and Tillement, 1999, Fundam. Clin. Pharmacol., 13, 16-26); biodegradable polymers, such as poly (DL-lactide-coglycolide) microspheres for sustained release delivery after intracerebral implantation (Emerich, DF et al, 1999, Cell Transplant, 8, 47-58) Alkermes, Inc. Cambridge, Mass.; and loaded nanoparticles, such as those made of polybutylcyanoacrylate, which can deliver drugs across the blood brain barrier and can alter neuronal uptake mechanisms (Prog Neuropsychopharmacol Biol Psychiatry, 23, 941-949, 1999). Other non-limiting examples of delivery strategies for the nucleic acid molecules of the instant invention include material described in Boado et al., 1998, J. Pharm. Sci., 87, 1308-1315; Tyler et al., 1999, FEBS Lett., 421, 280-284; Pardridge et al., 1995, PNAS USA., 92, 5592-5596; Boado, 1995, Adv. Drug Delivery Rev., 15, 73-107; Aldrian-Herrada et al., 1998, Nucleic Acids Res., 26, 4910-4916; and Tyler et al., 1999, PNAS USA., 96, 7053-7058.


[0132] The invention also features the use of the composition comprising surface-modified liposomes containing poly (ethylene glycol) lipids (PEG-modified, or long-circulating liposomes or stealth liposomes). These formulations offer a method for increasing the accumulation of drugs in target tissues. This class of drug carriers resists opsonization and elimination by the mononuclear phagocytic system (MPS or RES), thereby enabling longer blood circulation times and enhanced tissue exposure for the encapsulated drug (Lasic et al. Chem. Rev. 1995, 95, 2601-2627; Ishiwata et al., Chem. Pharm. Bull. 1995, 43, 1005-1011 ). All incorporated by reference herein. Such liposomes have been shown to accumulate selectively in tumors, presumably by extravasation and capture in the neovascularized target tissues (Lasic et al., Science 1995, 267, 1275-1276; Oku et al., 1995, Biochim. Biophys. Acta, 1238, 86-90). All incorporated by reference herein. The long-circulating liposomes enhance the pharmacokinetics and pharmacodynamics of DNA and RNA, particularly compared to conventional cationic liposomes which are known to accumulate in tissues of the MPS (Liu et al., J. Biol. Chem. 1995, 42, 24864-24870; Choi et al., International PCT Publication No. WO 96/10391; Ansell et al., International PCT Publication No. WO 96/10390; Holland et al., International PCT Publication No. WO 96/10392; all of which are incorporated by reference herein). Long-circulating liposomes are also likely to protect drugs from nuclease degradation to a greater extent compared to cationic liposomes, based on their ability to avoid accumulation in metabolically aggressive MPS tissues such as the liver and spleen.


[0133] In addition, the invention features the use of methods to deliver the nucleic acid molecules of the instant invention to hematopoietic cells, including monocytes and lymphocytes. These methods are described in detail by Hartmann et al., 1998, J. Phamacol. Exp. Ther., 285(2), 920-928; Kronenwett et al., 1998, Blood, 91(3), 852-862; Filion and Phillips, 1997, Biochim. Biophys. Acta., 1329(2), 345-356; Ma and Wei, 1996, Leuk. Res., 20(11/12), 925-930; and Bongartz et al., 1994, Nucleic Acids Research, 22(22), 4681-8. Such methods, as described above, include the use of free oligonucleotide, cationic lipid formulations, liposome formulations including pH sensitive liposomes and immunoliposomes, and bioconjugates including oligonucleotides conjugated to fusogenic peptides, for the transfection of hematopoietic cells with oligonucleotides.


[0134] The present invention also includes compositions prepared for storage or administration which include a pharmaceutically effective amount of the desired compounds in a pharmaceutically acceptable carrier or diluent. Acceptable carriers or diluents for therapeutic use are well known in the pharmaceutical art, and are described, for example, in Remington's Pharmaceutical Sciences, Mack Publishing Co. (A. R. Gennaro edit. 1985) hereby incorporated by reference herein. For example, preservatives, stabilizers, dyes and flavoring agents may be provided. These include sodium benzoate, sorbic acid and esters of p-hydroxybenzoic acid. In addition, antioxidants and suspending agents may be used.


[0135] A pharmaceutically effective dose is that dose required to prevent, inhibit the occurrence, or treat (alleviate a symptom to some extent, preferably all of the symptoms) of a disease state. The pharmaceutically effective dose depends on the type of disease, the composition used, the route of administration, the type of mammal being treated, the physical characteristics of the specific mammal under consideration, concurrent medication, and other factors which those skilled in the medical arts will recognize. Generally, an amount between 0.1 mg/kg and 100 mg/kg body weight/day of active ingredients is administered dependent upon potency of the negatively charged polymer.


[0136] The nucleic acid molecules of the present invention may also be administered to a patient in combination with other therapeutic compounds to increase the overall therapeutic effect. The use of multiple compounds to treat an indication may increase the beneficial effects while reducing the presence of side effects. Oxygen therapy, bronchodilators, corticosteroids, antibacterials, vaccinations, acetylcysteine, mucokinetic agents, and DNase (Pulmozyme) are non-limiting examples of compounds and/or methods that can be combined with or used in conjunction with the nucleic acid molecules (e.g. ribozymes and antisense molecules) of the instant invention. Those skilled in the art will recognize that other drug compounds and therapies can be similarly and readily combined with the nucleic acid molecules of the instant invention (e.g. ribozymes and antisense molecules) and are, therefore, within the scope of the instant invention. Alternatively, certain of the nucleic acid molecules of the instant invention can be expressed within cells from eukaryotic promoters (e.g., Izant and Weintraub, 1985, Science, 229, 345; McGarry and Lindquist, 1986, Proc. Natl. Acad. Sci., USA 83, 399; Scanlon et al., 1991, Proc. Natl. Acad. Sci. USA, 88, 10591-5; Kashani-Sabet et al., 1992, Antisense Res. Dev., 2, 3-15; Dropulic et al., 1992, J Virol., 66, 1432-41; Weerasinghe et al., 1991, J. Virol., 65, 5531-4; Ojwang et al., 1992, Proc. Natl. Acad. Sci. USA, 89, 10802-6; Chen et al., 1992, Nucleic Acids Res., 20, 4581-9; Sarver et al., 1990 Science, 247, 1222-1225; Thompson et al., 1995, Nucleic Acids Res., 23, 2259; Good et al., 1997, Gene Therapy, 4, 45; all of the references are hereby incorporated in their totality by reference herein). Those skilled in the art realize that any nucleic acid can be expressed in eukaryotic cells from the appropriate DNA/RNA vector. The activity of such nucleic acids can be augmented by their release from the primary transcript by a ribozyme (Draper et al., PCT WO 93/23569, and Sullivan et al., PCT WO 94/02595; Ohkawa et al., 1992, Nucleic Acids Symp. Ser., 27, 15-6; Taira et al., 1991, Nucleic Acids Res., 19, 5125-30; Ventura et al., 1993, Nucleic Acids Res., 21, 3249-55; Chowrira et al., 1994, J. Biol. Chem., 269, 25856; all of these references are hereby incorporated in their totalities by reference herein).


[0137] In another aspect of the invention, RNA molecules of the present invention are preferably expressed from transcription units (see, for example, Couture et al., 1996, TIG., 12, 510) inserted into DNA or RNA vectors. The recombinant vectors are preferably DNA plasmids or viral vectors. Ribozyme expressing viral vectors could be constructed based on, but not limited to, adeno-associated virus, retrovirus, adenovirus, or alphavirus. Preferably, the recombinant vectors capable of expressing the nucleic acid molecules are delivered as described above, and persist in target cells. Alternatively, viral vectors may be used that provide for transient expression of nucleic acid molecules. Such vectors might be repeatedly administered as necessary. Once expressed, the nucleic acid molecule binds to the target mRNA. Delivery of nucleic acid molecule expressing vectors could be systemic, such as by intravenous or intramuscular administration, by administration to target cells explanted from the patient followed by reintroduction into the patient, or by any other means that would allow for introduction into the desired target cell (for a review, see Couture et al., 1996, TIG., 12,510).


[0138] In one aspect, the invention features an expression vector comprising a nucleic acid sequence encoding at least one of the nucleic acid molecules disclosed in the instant invention. The nucleic acid sequence encoding the nucleic acid molecule of the instant invention is operably linked in a manner which allows expression of that nucleic acid molecule.


[0139] In another aspect, the invention features an expression vector comprising: a) a transcription initiation region (e.g., eukaryotic pol I, II or Ell initiation region); b) a transcription termination region (e.g., eukaryotic pol I, II or III termination region); c) a nucleic acid sequence encoding at least one of the nucleic acid catalyst of the instant invention; and wherein said sequence is operably linked to said initiation region and said termination region, in a manner which allows expression and/or delivery of said nucleic acid molecule. The vector may optionally include an open reading frame (ORF) for a protein operably linked on the 5′ side or the 3′-side of the sequence encoding the nucleic acid catalyst of the invention; and/or an intron (intervening sequences).


[0140] Transcription of the nucleic acid molecule sequences are driven from a promoter for eukaryotic RNA polymerase I (pol I), RNA polymerase II (pol II), or RNA polymerase III (pol III). Transcripts from pol II or pol HI promoters will be expressed at high levels in all cells; the levels of a given pol II promoter in a given cell type will depend on the nature of the gene regulatory sequences (enhancers, silencers, etc.) present nearby. Prokaryotic RNA polymerase promoters are also used, providing that the prokaryotic RNA polymerase enzyme is expressed in the appropriate cells (Elroy-Stein and Moss, 1990, Proc. Natl. Acad. Sci. USA, 87, 6743-7; Gao and Huang 1993, Nucleic Acids Res., 21, 2867-72; Lieber et al., 1993, Methods Enzymol., 217, 47-66; Zhou et al., 1990, Mol. Cell. Biol., 10, 4529-37). All of these references are incorporated by reference herein.


[0141] Several investigators have demonstrated that nucleic acid molecules, such as ribozymes expressed from such promoters can function in mammalian cells (e.g. Kashani-Sabet et al., 1992, Antisense Res. Dev., 2, 3-15; Ojwang et al., 1992, Proc. Natl. Acad. Sci. USA, 89, 10802-6; Chen et al., 1992, Nucleic Acids Res., 20, 4581-9; Yu et al., 1993, Proc. Natl. Acad. Sci. USA, 90, 6340-4; L'Huillier et al., 1992, EMBO J., 11, 4411-8; Lisziewicz et al., 1993, Proc. Natl. Acad. Sci. U.S.A, 90, 8000-4; Thompson et al., 1995, Nucleic Acids Res., 23, 2259; and Sullenger & Cech, 1993, Science, 262, 1566). More specifically, transcription units such as the ones derived from genes encoding U6 small nuclear (snRNA), transfer RNA (tRNA) and adenovirus VA RNA are useful in generating high concentrations of desired RNA molecules such as ribozymes in cells (Thompson et al., supra; Couture and Stinchcomb, 1996, supra; Noonberg et al, 1994, Nucleic Acid Res., 22, 2830; Noonberg et al, U.S. Pat. No. 5,624,803; Good et al., 1997, Gene Ther., 4, 45; and Beigelman et al., International PCT Publication No. WO 96/18736; all of these publications are incorporated by reference herein. The above ribozyme transcription units can be incorporated into a variety of vectors for introduction into mammalian cells, including but not restricted to, plasmid DNA vectors, viral DNA vectors (such as adenovirus or adeno-associated virus vectors), or viral RNA vectors (such as retroviral or alphavirus vectors) (for a review, see Couture and Stinchcomb, 1996, supra).


[0142] In yet another aspect, the invention features an expression vector comprising a nucleic acid sequence encoding at least one of the nucleic acid molecules of the invention, in a manner which allows expression of that nucleic acid molecule. The expression vector comprises in one embodiment; a) a transcription initiation region; b) a transcription termination region; c) a nucleic acid sequence encoding at least one said nucleic acid molecule; and wherein said sequence is operably linked to said initiation region and said termination region, in a manner which allows expression and/or delivery of said nucleic acid molecule.


[0143] In another preferred embodiment, the expression vector comprises: a) a transcription initiation region; b) a transcription termination region; c) an open reading frame; d) a nucleic acid sequence encoding at least one said nucleic acid molecule, wherein said sequence is operably linked to the 3′-end of said open reading frame; and wherein said sequence is operably linked to said initiation region, said open reading frame and said termination region, in a manner which allows expression and/or delivery of said nucleic acid molecule.


[0144] In yet another embodiment the expression vector comprises: a) a transcription initiation region; b) a transcription termination region; c) an intron; d) a nucleic acid sequence encoding at least one said nucleic acid molecule; and wherein said sequence is operably linked to said initiation region, said intron and said termination region, in a manner which allows expression and/or delivery of said nucleic acid molecule.


[0145] In another embodiment, the expression vector comprises: a) a transcription initiation region; b) a transcription termination region; c) an intron; d) an open reading frame; e) a nucleic acid sequence encoding at least one said nucleic acid molecule, wherein said sequence is operably linked to the 3′-end of said open reading frame; and wherein said sequence is operably linked to said initiation region, said intron, said open reading frame and said termination region, in a manner which allows expression and/or delivery of said nucleic acid molecule.



EXAMPLES

[0146] The following are non-limiting examples showing the selection, isolation, synthesis and activity of nucleic acids of the instant invention.


[0147] The following examples demonstrate the selection and design of Antisense, hammerhead, DNAzyme, NCH, Amberzyme, Zinzyme, or G-Cleaver ribozyme molecules and binding/cleavage sites within CLCA1 RNA.



Example 1


Reporter System

[0148] Applicant used a target discovery and target validation approach to finding genes that are involved in chronic mucous hypersecretion. In order to discover genes playing a role in the expression of mucins, a readily assayable reporter system was devised. The reporter system consists of a plasmid construct, termed pMUC5AC-EGFP, bearing a gene coding for Green Fluorescent Protein (GFP). The promoter region of the GFP gene is replaced by a portion of the Mucin 5AC promoter sufficient to direct efficient transcription of the GFP gene. The plasmid also contains the neomycin drug resistance gene.



Example 2


Host Cell Line for Target Discovery

[0149] The cell line selected as host for these studies, NCI-H292 (ATCC CRL-1848), is derived from a human lung mucoepidermoid carcinoma. The cells retain mucoepidermoid characteristics in culture and endogenously express mucin 5AC and mucin 2. The pMUC5AC-EGFP plasmid was transfected into NCI-H292 using a cationic lipid formulation. Following transfection, the cells were subjected to limiting dilution cloning under selection by 600 μg/mL Geneticin. Cells retaining the pMUC5AC-EGFP plasmid survive the Geneticin treatment and form colonies derived from single surviving cells. The resulting clonal cell lines were screened by flow cytometry for the capacity to upregulate GFP production directed by the Mucin 5AC promoter. Treating the cells with sterilized M9 bacterial medium in which Pseudomonas aeruginosa had been cultured (Pseudomonas conditioned medium, PCM) induced the mucin promoter. The PCM is supplemented with phorbol myristate acetate (PMA).


[0150] A clonal cell line highly responsive to mucin promoter induction, designated H292/MUC5AC/EGFP Clone8 (H292 Clone 8) was selected as the reporter line for subsequent studies. The process for Target Discovery is described in Jarvis et al., International PCT publication No. WO 98/50530, incorporated by reference herein in its entirety including the Figures.



Example 3


Ribozyme Library Construction

[0151] A ribozyme library was constructed with oligonucletides containing ribozymes with two randomized regions comprising six-nucleotide binding “arms” (Stem I and Stem HI of a ribozyme-substrate complex). Oligo sequence 5′ and 3′ of the ribozyme contains restriction endonuclease cleavage sites for cloning. The 3′ trailing sequence forms a stem-loop for priming DNA polymerase extension to form a double stranded molecule. The double-stranded ribozyme library was cloned into the U6+27 transcription unit located in the 5′ LTR region of a retroviral vector containing the human nerve growth factor receptor (hNGFr) reporter gene.


[0152] Positioning the U6+27/ribozyme transcription unit in the 5′ LTR results in a duplication of the transcription unit when the vector integrates into the host cell genome. As a result, the ribozyme is transcribed by RNA polymerase HI from U6+27 and by RNA polymerase II activity directed by the 5′ LTR. The ribozyme library was packaged into retroviral particles that were used to infect and transduce H292 Clone 8 cells. Assay of the hNGFr reporter indicated that 50% to 60% of Clone 8 cells incorporated the ribozyme construct. FIGS. 5A and 5B describe the generalized scheme used in the ribozyme library construction and target discovery. By “randomized region” is meant a region of completely random sequence and/or partially random sequence. By completely random sequence is meant a sequence wherein theoretically there is equal representation of A, T, G and C nucleotides or modified derivatives thereof, at each position in the sequence. By partially random sequence is meant a sequence wherein there is an unequal representation of A, T, G and C nucleotides or modified derivatives thereof, at each position in the sequence. A partially random sequence can therefore have one or more positions of complete randomness and one or more positions with defined nucleotides.



Example 4


Enriching for Non-responders to Mucin Induction

[0153] Sorting of ribozyme library-containing cells was performed to enrich for cells that produce less GFP after treatment with PCM and PMA. Lower GFP production may be due to ribozyme action upon genes involved in the activation of the mucin promoter. Alternatively, ribozymes may directly target the mucin/GFP transcript resulting in reduced GFP expression.


[0154] Cells were seeded at a density of 1×106 per 150 cm2 style cell culture flasks. After 72 hours the standard cell culture medium was replaced with medium without fetal bovine serum. After 24 hours of serum deprivation the cells were treated with serum-containing medium supplemented with PCM (to 40%) and PMA (to 50 nM) to induced GFP production via the mucin promoter. After 20 to 22 hours, cells were monitored for GFP level on a FACStar Plus cell sorter.


[0155] Sorting was performed if 90% of ribozyme library cells from an unsorted control sample were induced to produce GFP above background levels. Two cell fractions were collected in each round of sorting.


[0156] In the initial sort the M1 gate collected cells in luminescence channels 1 to 4.5; those cells with the lowest GFP signal (5% of the induced population). The M2 sort gate collected cells in luminescence channels 4.5 to 20; cells with low GFP signal (10% of the induced population). The M1 and M2 fractions together represented the 15% of the induced population responding least to the GFP induction treatment. In order to assure that the diversity of the ribozyme library was represented 2.3×106 cells were collected in the M1 fraction and 4.6×106 cells were collected in the M2 fraction. The M1 and M2 fractions wee cultured separately and representative portions of each were cryopreserved after each round of sorting.


[0157] When treated with PCM and PMA prior to a second round of sorting, cells from both the M1 and M2 fractions responded as before with >90% of the cells producing elevated levels of GFP. The same sorting criteria and sort gates were used in the second round. As in the first round of sorting the M1 sort gate collected 5% of the treated cells (those with little or no GFP) and the M2 gate collected 10% of the cells. Two more rounds of sorting were performed using the same sorting criteria.


[0158] Prior to the third round of sorting the M1 fraction showed a three-fold enrichment of GFP negative cells. Prior to the fourth round of sorting both the M1 and M2 fractions were significantly enriched in cells unresponsive to the GFP induction treatment.


[0159] Following the third round of sorting the M1 fraction was selected to generate a database of ribozymes present in the sorted cells.



Example 5


Recovery of Ribozyme Sequence from Sorted Cells

[0160] Genomic DNA was obtained from sorted ribozyme library cells by standard methods. Nested polymerase chain reaction (PCR) primers (Sequence ID Nos. 5468 and 5469) that hybridized to the retroviral vector 5′ and 3′ of the ribozyme were used to recover and amplify the ribozyme sequences from the Clone 8 library cell DNA. The PCR product was ligated into a bacterial cloning vector. Two methods were developed to use the recovered ribozyme library, in plasmid form, to generate a database of ribozyme binding arm sequences. In the first approach the library was cloned into E. coli. DNA was prepared by plasmid isolation from bacterial colonies or by direct colony PCR and ribozyme arm sequence was determined. Over 450 sequences have been obtained by this method. A second method used the ribozyme library to transfect H292 Clone 8 cells. Clonal lines of stably transfected cells were established and induced with PCM and PMA. Those lines which failed to respond to GFP induction were probed by PCR for single ribozyme integration events. Over 300 sequences were obtained in this manner. The unique ribozyme sequences obtained by both methods were added to a Target Sequence Tag (TST) database.



Example 6


Bioinformatics

[0161] After sequencing 760 recovered ribozymes 171 unique sequences were found. Of the unique sequences, 91 have been recovered once and 80 have been found multiple times. Most of the repeated sequences have been found 2 to 11 times. One sequence has been recovered 145 times. The diversity of the sequences obtained indicates that the sorted cells are a promising source of information leading to target discovery.


[0162] Ribozyme binding arm sequences were compared to public and private gene data banks. Gene matches were compiled according to perfect and imperfect matches. Potential gene targets were categorized by the number of different ribozyme sequences matching each gene. Multiple ribozyme matches have been found for 180 genes. Genes with more than one perfect ribozyme match were given close attention. A total of 34 genes have been verified to date to have multiple perfect ribozyme matches. Of those at least 17 have protein products of known function.


[0163] Two perfect ribozyme matches were found for human calcium activated chloride channel-1 (hCLCA1). Each ribozyme matches at two sites in the hCLCA1 gene. A third sorted library ribozyme sequence “hits” hCLCA1 but has a single nucleotide mismatch.



Example 7


Selection of hCLCA1 for Validation

[0164] The selection of hCLCA1 as a candidate for target validation was based on bioinformatics and on emerging data in murine models of mucous hypersecretion in the trachea and lung. Two ribozymes (Seq. ID Nos. 2332 and 2273) recovered from cells that no longer respond to mucin promoter/GFP induction match perfectly to hCLCA1. A third has a single mismatch. Evidence from two murine models indicates a correlation between mucous hypersecretion in the lung and strong upregulation of gob-5 (GenBank ABO17156), a murine homologue of hCLCA1.



Example 8


Validation of hCLCA1

[0165] To validate hCLCA1 as a regulator of MUC5AC expression, GeneBloc reagents were designed (Table IX) to the hCLCA1 cDNA sequence (GenBank AF039400). GeneBloc reagents are complexed with a cationic lipid formulation prior to administration to H292/MUC5AC/GFP Clone 8 cells. Concentrations of the GeneBloc reagents administered range from 30 nM to 120 nM at cationic lipid concentrations of 4-6 μg/mL. Cells are treated with GeneBloc reagents for 72 to 96 30 hours. Before the termination of GeneBloc treatment, PCM (to 40 %) and PMA (to 50 nM) are added to induce the MUC5AC promoter. After twenty hours of induction the cells are harvested and assayed for phenotypic and molecular parameters. Reduced GFP expression in GeneBloc treated cells (measured by flow cytometry) is taken as evidence for validation of hCLCA1. Knockdown of hCLCA1 RNA in GeneBloc treated cells can correlate with reduced endogenous MUC5AC RNA and reduced GFP RNA (from the MUC5AC/GFP construct) to complete validation of hCLCA1.



Example 9


Identification of Potential Target Sites in Human CLCA1 RNA

[0166] The sequence of human CLCA1 is screened for accessible sites using a computer-folding algorithm. Regions of the RNA are identified that do not form secondary folding structures. These regions contain potential ribozyme and/or antisense binding/cleavage sites. The sequences of these binding/cleavage sites are shown in Tables III-IX.



Example 10


Selection of Enzymatic Nucleic Acid Cleavage Sites in Human CLCA1 RNA

[0167] Ribozyme target sites are chosen by analyzing sequences of Human CLCA1 (GenBank accession numbers: NM001285 and AF039400) and prioritizing the sites on the basis of folding. Ribozymes are designed that could bind each target and are individually analyzed by computer folding (Christoffersen et al., 1994 J. Mol. Struc. Theochem, 311, 273; Jaeger et al., 1989, Proc. Natl. Acad. Sci. USA, 86, 7706) to assess whether the ribozyme sequences fold into the appropriate secondary structure. Those ribozymes with unfavorable intramolecular interactions between the binding arms and the catalytic core are eliminated from consideration. As noted below, varying binding arm lengths can be chosen to optimize activity. Generally, at least 5 bases on each arm are able to bind to, or otherwise interact with, the target RNA.



Example 11


Chemical Synthesis and Purification of Ribozymes and Antisense for Efficient Cleavage and/or blocking of CLCA1 RNA

[0168] Ribozymes and antisense constructs are designed to anneal to various sites in the RNA message. The binding arms of the ribozymes are complementary to the target site sequences described above, while the antisense constructs are fully complimentary to the target site sequences described above. The ribozymes and antisense constructs were chemically synthesized. The method of synthesis used followed the procedure for normal RNA synthesis as described above and in Usman et al., (1987 J. Am. Chem. Soc., 109, 7845), Scaringe et al., (1990 Nucleic Acids Res., 18, 5433) and Wincott et al., supra, and made use of common nucleic acid protecting and coupling groups, such as dimethoxytrityl at the 5′-end, and phosphoramidites at the 3′-end. The average stepwise coupling yields were typically >98%.


[0169] Ribozymes and antisense constructs are also synthesized from DNA templates using bacteriophage T7 RNA polymerase (Milligan and Uhlenbeck, 1989, Methods Enzymol. 180, 51). Ribozymes and antisense constructs are purified by gel electrophoresis using general methods or are purified by high pressure liquid chromatography (HPLC; see Wincott et al., supra; the totality of which is hereby incorporated herein by reference) and are resuspended in water. The sequences of the chemically synthesized ribozymes and antisense constructs used in this study are shown below in Table III-IX.


[0170] Indications


[0171] Particular conditions and disease states that can be associated with CLCA1 expression modulation include but are not limited to Chronic Obstructive Pulmonary Disease (COPD), chronic bronchitis, asthma, cystic fibrosis, obstructive bowel syndrome, and any other diseases or conditions that are related to or will respond to the levels of CLCA1 in a cell or tissue, alone or in combination with other therapies.


[0172] The present body of knowledge in CLCA1 research indicates the need for methods to assay CLCA1 activity and for compounds that can regulate CLCA1 expression for research, diagnostic, and therapeutic use.


[0173] The nucleic acid molecules of the present invention may also be administered to a patient in combination with other therapeutic compounds to increase the overall therapeutic effect. The use of multiple compounds to treat an indication may increase the beneficial effects while reducing the presence of side effects. Oxygen therapy, bronchodilators, corticosteroids, antibacterials, vaccinations, acetylcysteine, mucokinetic agents, and DNase (Pulmozyme), are non-limiting examples of methods and/or treatments that can be used in combination with nucleic acid molecules of the invention. Those skilled in the art will recognize that other drug compounds and therapies can be similarly and readily combined with the nucleic acid molecules of the instant invention (e.g. ribozymes and antisense molecules) and are, therefore, within the scope of the instant invention.


[0174] Cell Culture


[0175] The cell culture system described in Example 8 can be used to evaluate nucleic acid molecules of the invention for efficacy in CLCA1 and mucin modulation.


[0176] Animal Models


[0177] Numerous reports can be found which describe animal models relevant to disease states such as COPD and cystic fibrosis. These models can be used to determine efficacy of the nucleic acid molecules of the instant invention targeting such disease states or conditions. Animal models for chronic pulmonary disease (COPD) are described by Shapiro, 2000, Am. J. Respir. Cell Mol. BioL, 22(1), 4-7; Hogg, 1998, Ika Daigaku Zasshi, 56(3), 429-432; and Garssen et al., 1997, Inhalation Toxicol., 9(6), 581-599. Animal models for cystic fibrosis are described by Kent et al., 1997, J. Clin. Invest., 100(12), 3060-3069; Hill et al., 1997, 62(1), 113-122; Grubb and Gabriel, 1997, Am. J. Physiol., 272, G258-G266; Rozmahel, 1996, From: Diss. Abstr. Int. B 1997, 57(8), 4863; Van Doominck et al., 1995, EMBOJ., 14(18), 4403-11; and Zeiher et al., 1995, J. Clin. Invest., 96(4), 2051-64.


[0178] Diagnostic Uses


[0179] The nucleic acid molecules of this invention (e.g., ribozymes) may be used as diagnostic tools to examine genetic drift and mutations within diseased cells or to detect the presence of CLCA1 RNA in a cell. The close relationship between ribozyme activity and the structure of the target RNA allows the detection of mutations in any region of the molecule which alters the base-pairing and three-dimensional structure of the target RNA. By using multiple ribozymes described in this invention, one may map nucleotide changes which are important to RNA structure and function in vitro, as well as in cells and tissues. Cleavage of target RNAs with ribozymes may be used to inhibit gene expression and define the role (essentially) of specified gene products in the progression of disease. In this manner, other genetic targets may be defined as important mediators of the disease. These experiments will lead to better treatment of the disease progression by affording the possibility of combinational therapies (e.g., multiple ribozymes targeted to different genes, ribozymes coupled with known small molecule inhibitors, or intermittent treatment with combinations of ribozymes and/or other chemical or biological molecules). Other in vitro uses of ribozymes of this invention are well known in the art, and include detection of the presence of mRNAs associated with CLCA1 -related condition. Such RNA is detected by determining the presence of a cleavage product after treatment with a ribozyme using standard methodology.


[0180] In a specific example, ribozymes which can cleave only wild-type or mutant forms of the target RNA are used for the assay. The first ribozyme is used to identify wild-type RNA present in the sample and the second ribozyme will be used to identify mutant RNA in the sample. As reaction controls, synthetic substrates of both wild-type and mutant RNA will be cleaved by both ribozymes to demonstrate the relative ribozyme efficiencies in the reactions and the absence of cleavage of the “non-targeted” RNA species. The cleavage products from the synthetic substrates will also serve to generate size markers for the analysis of wild-type and mutant RNAs in the sample population. Thus, each analysis can require two ribozymes, two substrates and one unknown sample, which will be combined into six reactions. The presence of cleavage products will be determined using an RNAse protection assay so that full-length and cleavage fragments of each RNA can be analyzed in one lane of a polyacrylamide gel. It is not absolutely required to quantify the results to gain insight into the expression of mutant RNAs and putative risk of the desired phenotypic changes in target cells. The expression of mRNA whose protein product is implicated in the development of the phenotype (i.e., CLCA1) is adequate to establish risk. If probes of comparable specific activity are used for both transcripts, then a qualitative comparison of RNA levels will be adequate and will decrease the cost of the initial diagnosis. Higher mutant form to wild-type ratios will be correlated with higher risk whether RNA levels are compared qualitatively or quantitatively.


[0181] Additional Uses


[0182] Potential usefulness of sequence-specific enzymatic nucleic acid molecules of the instant invention might have many of the same applications for the study of RNA that DNA restriction endonucleases have for the study of DNA (Nathans et al., 1975 Ann. Rev. Biochem. 44:273). For example, the pattern of restriction fragments could be used to establish sequence relationships between two related RNAs, and large RNAs could be specifically cleaved to fragments of a size more useful for study. The ability to engineer sequence specificity of the enzymatic nucleic acid molecule is ideal for cleavage of RNAs of unknown sequence. Applicant describes the use of nucleic acid molecules to down-regulate gene expression of target genes in bacterial, microbial, fungal, viral, and eukaryotic systems including plant, or mammalian cells.


[0183] All patents and publications mentioned in the specification are indicative of the . levels of skill of those skilled in the art to which the invention pertains. All references cited in this disclosure are incorporated by reference to the same extent as if each reference had been incorporated by reference in its entirety individually.


[0184] One skilled in the art would readily appreciate that the present invention is well adapted to carry out the objects and obtain the ends and advantages mentioned, as well as those inherent therein. The methods and compositions described herein as presently representative of preferred embodiments are exemplary and are not intended as limitations on the scope of the invention. Changes therein and other uses will occur to those skilled in the art, which are encompassed within the spirit of the invention, are defined by the scope of the claims.


[0185] It will be readily apparent to one skilled in the art that varying substitutions and modifications may be made to the invention disclosed herein without departing from the scope and spirit of the invention. Thus, such additional embodiments are within the scope of the present invention and the following claims.


[0186] The invention illustratively described herein suitably may be practiced in the absence of any element or elements, limitation or limitations which is not specifically disclosed herein. Thus, for example, in each instance herein any of the terms “comprising”, “consisting essentially of” and “consisting of” may be replaced with either of the other two terms. The terms and expressions which have been employed are used as terms of description and not of limitation, and there is no intention that in the use of such terms and expressions of excluding any equivalents of the features shown and described or portions thereof, but it is recognized that various modifications are possible within the scope of the invention claimed. Thus, it should be understood that although the present invention has been specifically disclosed by preferred embodiments, optional features, modification and variation of the concepts herein disclosed may be resorted to by those skilled in the art, and that such modifications and variations are considered to be within the scope of this invention as defined by the description and the appended claims.


[0187] In addition, where features or aspects of the invention are described in terms of Markush groups or other grouping of alternatives, those skilled in the art will recognize that the invention is also thereby described in terms of any individual member or subgroup of members of the Markush group or other group.


[0188] Other embodiments are within the following claims.
1TABLE ICharacteristics of naturally occurring ribozymesGroup I IntronsSize: ˜150 to >1000 nucleotides.Requires a U in the target sequence immediately 5′ of the cleavage site.Binds 4-6 nucleotides at the 5′-side of the cleavage site.Reaction mechanism: attack by the 3′-OH of guanosine to generatecleavage products with 3′-OH and 5′-guanosine.Additional protein cofactors required in some cases to help folding andmaintainance of the active structure.Over 300 known members of this class. Found as an intervening sequencein Tetrahymena thermophila rRNA, fungal mitochondria, chloroplasts,phage T4, blue-green algae, and others.Major structural features largely established through phylogeneticcomparisons, mutagenesis, and biochemical studies [i,ii].Complete kinetic framework established for one ribozyme [iii,iv,v,vi].Studies of ribozyme folding and substrate docking underway [vii,viii,ix].Chemical modification investigation of important residues well established[x,xi]The small (4-6 nt) binding site may make this ribozyme too non-specificfor targeted RNA cleavage, however, the Tetrahymena group I intron hasbeen used to repair a “defective” □-galactosidase message by the ligationof new □-galactosidase sequences onto the defective message [xii].RNAse P RNA (M1 RNA)Size: ˜290 to 400 nucleotides.RNA portion of a ubiquitous ribonucleoprotein enzyme.Cleaves tRNA precursors to form mature tRNA [xiii].Reaction mechanism: possible attack by M2+-OH to generate cleavageproducts with 3′-OH and 5′-phosphate.RNAse P is found throughout the prokaryotes and eukaryotes. The RNAsubunit has been sequenced from bacteria, yeast, rodents, and primates.Recruitment of endogenous RNAse P for therapeutic applications ispossible through hybridization of an External Guide Sequence (EGS) tothe target RNA [xiv,xv]Important phosphate and 2′-OH contacts recently identified [xvi,xvii]Group II IntronsSize: >1000 nucleotides.Trans cleavage of target RNAs recently demonstrated [xviii,xix].Sequence requirements not fully determined.Reaction mechanism: 2′-OH of an internal adenosine generates cleavageproducts with 3′-OH and a “lariat” RNA containing a 3′-5′ and a 2′-5′branch point.Only natural ribozyme with demonstrated participation in DNA cleavage[xx,xxi] in addition to RNA cleavage and ligation.Major structural features largely established through phylogeneticcomparisons [xxii].Important 2′-OH contacts beginning to be identified [xxiii]Kinetic framework under development [xxiv]Neurospora VS RNASize: ˜144 nucleotides.Trans cleavage of hairpin target RNAs recently demonstrated [xxv].Sequence requirements not fully determined.Reaction mechanism: attack by 2′-OH 5′ to the scissile bond to generatecleavage products with 2′,3′-cyclic phosphate and 5′-OH ends.Binding sites and structural requirements not fully determined.Only 1 known member of this class. Found in Neurospora VS RNA.Hammerhead Ribozyme(see text for references)Size: ˜13 to 40 nucleotides.Requires the target sequence UH immediately 5′ of the cleavage site.Binds a variable number nucleotides on both sides of the cleavage site.Reaction mechanism: attack by 2′-OH 5′ to the scissile bond to generatecleavage products with 2′,3′-cyclic phosphate and 5′-OH ends.14 known members of this class. Found in a number of plant pathogens(virusoids) that use RNA as the infectious agent.Essential structural features largely defined, including 2 crystal structures[xxvi,xxvii]Minimal ligation activity demonstrated (for engineering through in vitroselection) [xxviii]Complete kinetic framework established for two or more ribozymes [xxix].Chemical modification investigation of important residues well established[xxx].Hairpin RibozymeSize: ˜50 nucleotides.Requires the target sequence GUC immediately 3′ of the cleavage site.Binds 4-6 nucleotides at the 5′-side of the cleavage site and a variablenumber to the 3′-side of the cleavage site.Reaction mechanism: attack by 2′-OH 5′ to the scissile bond to generatecleavage products with 2′,3′-cyclic phosphate and 5′-OH ends.3 known members of this class. Found in three plant pathogen (satelliteRNAs of the tobacco ringspot virus, arabis mosaic virus and chicoryyellow mottle virus) which uses RNA as the infectious agent.Essential structural features largely defined [xxxi,xxxii,xxxiii,xxxiv]Ligation activity (in addition to cleavage activity) makes ribozymeamenable to engineering through in vitro selection [xxxv]Complete kinetic framework established for one ribozyme [xxxvi].Chemical modification investigation of important residues begun[xxxvii,xxxviii].Hepatitis Delta Virus (HDV) RibozymeSize: ˜60 nucleotides.Trans cleavage of target RNAs demonstrated [xxxix].Binding sites and structural requirements not fully determined, although nosequences 5′ of cleavage site are required. Folded ribozyme contains apseudoknot structure [xl].Reaction mechanism: attack by 2′-OH 5′ to the scissile bond to generatecleavage products with 2′,3′-cyclic phosphate and 5′-OH ends.Only 2 known members of this class. Found in human HDV.Circular form of HDV is active and shows increased nuclease stability[xli]iMichel, Francois; Westhof, Eric. Slippery substrates. Nat. Struct. Biol. (1994), 1(1), 5-7. iiLisacek, Frederique; Diaz, Yolande; Michel, Francois. Automatic identification of group I intron cores in genomic DNA sequences. J. Mol. Biol. (1994), 235(4), 1206-17. iiiHerschlag, Daniel; Cech, Thomas R., Catalysis of RNA cleavage by the Tetrahymena thermophila ribozyme. 1. Kinetic description of the reaction of an RNA substrate complementary to the active site. Biochemistry (1990), 29(44), 10159-71. ivHerschlag, Daniel; Cech, Thomas R., Catalysis of RNA cleavage by the Tetrahymena thermophila ribozyme. 2. Kinetic description of the reaction of an RNA substrate that forms a mismatch at the active site. Biochemistry (1990), 29(44), 10172-80. vKnitt, Deborah S.; Herschlag, Daniel. pH Dependencies of the Tetrahymena Ribozyme Reveal an Unconventional Origin of an Apparent pKa. Biochemistry (1996), 35(5), 1560-70. viBevilacqua, Philip C.; Sugimoto, Naoki; Turner, Douglas H., A mechanistic framework for the second step of splicing catalyzed by the Tetrahymena ribozyme. Biochemistry (1996), 35(2), 648-58. viiLi, Yi; Bevilacqua, Philip C.; Mathews, David; Turner, Douglas H., Thermodynamic and activation parameters for binding of a pyrene-labeled substrate by the Tetrahymena ribozyme: docking is not diffusion-controlled and is driven by a favorable entropy change. Biochemistry (1995), 34(44), 14394-9. viiiBanerjee, Aloke Raj; Turner, Douglas H., The time dependence of chemical modification reveals slow steps in the folding of a group I ribozyme. Biochemistry (1995), 34(19), 6504-12. ixZarrinkar, Patrick P.; Williamson, James R., The P9.1-P9.2 peripheral extension helps guide folding of the Tetrahymena ribozyme. Nucleic Acids Res. (1996), 24(5), 854-8. xStrobel, Scott A.; Cech, Thomas R., Minor groove recognition of the conserved G.cntdot.U Pair at the Tetrahymena ribozyme reaction site. Science (Washington, D. C.) (1995), 267(5198), 675-9. xiStrobel, Scott A.; Cech, Thomas R., Exocyclic Amine of the Conserved G.cntdot.U Pair at the Cleavage Site of the Tetrahymena Ribozyme Contributes to 5′-Splice Site Selection and Transition State Stabilization. Biochemistry (1996), 35(4), 1201-11. xiiSullenger, Bruce A.; Cech, Thomas R., Ribozyme-mediated repair of defective mRNA by targeted trans-splicing. Nature (London) (1994), 371(6498), 619-22. xiiiRobertson, H.D.; Altman, S.; Smith, J. D. J. Biol. Chem., 247, 5243-5251 (1972). xivForster, Anthony C.; Altman, Sidney. External guide sequences for an RNA enzyme. Science (Washington, D. C., 1883-) (1990), 249(4970), 783-6. xvYuan, Y.; Hwang, E. S.; Altman, S. Targeted cleavage of mRNA by human RNase P. Proc. Natl. Acad. Sci. USA (1992) 89, 8006-10. xviHarris, Michael E.; Pace, Norman R., Identification of phosphates involved in catalysis by the ribozyme RNase P RNA. RNA (1995), 1(2), 210-18. xviiPan, Tao; Lana, Andrew; Zhong, Kun. Probing of tertiary interactions in RNA: 2-hydroxyl-base contacts between the RNase P RNA and pre-tRNA. Proc. Natl. Acad. Sci. U.S.A. (1995), 92(26), 12510-14. xviiiPyle, Anna Marie; Green, Justin B.. Building a Kinetic Framework for Group II Intron Ribozyme Activity: Quantitation of Interdomain Binding and Reaction Rate. Biochemistry (1994), 33(9), 2716-25. xixMichels, William J. Jr.; Pyle, Anna Marie. Conversion of a Group II Intron into a New Multiple-Turnover Ribozyme that Selectively Cleaves Oligonucleotides: Elucidation of Reaction Mechanism and Structure/Function Relationships. Biochemistry (1995), 34(9), 2965-77. xxZimmerly, Steven; Guo, Huatao; Eskes, Robert; Yang, Jian; Perlman, Philip S.; Lambowitz, Alan M., A group II intron RNA is a catalytic component of a DNA endonuclease involved in intron mobility. Cell (Cambridge, Mass.) (1995), 83(4), 529-38. xxiGriffin, Edmund A., Jr.; Qin, Zhifeng; Michels, Williams J., Jr.; Pyle, Anna Marie. Group II intron ribozymes that cleave DNA and RNA linkages with similar efficiency, and lack contacts with substrate 2-hydroxyl groups. Chem. Biol. (1995), 2(11), 761-70. xxiiMichel, Francois; Ferat, Jean Luc. Structure and activities of group II introns. Annu. Rev. Biochem. (1995), 64, 435-61. xxiiiAbramovitz, Dana L.; Friedman, Richard A.; Pyle, Anna Marie. Catalytic role of 2′-hydroxyl groups within a group II intron active site. Science (Washington, D.C.) (1996), 271(5254), 1410-13. xxivDaniels, Danette L.; Michels, William J., Jr.; Pyle, Anna Marie. Two competing pathways for self-splicing by group II introns: a quantitative analysis of in vitro reaction rates and products. J. Mol. Biol. (1996), 256(1), 31-49. xxvGuo, Hans C. T.; Collins, Richard A.. Efficient trans-cleavage of a stem-loop RNA substrate by a ribozyme derived from Neurospora VS RNA. EMBO J. (1995), 14(2), 368-76. xxviScott, W. G., Finch, J. T., Aaron, K. The crystal structure of an all RNA hammerhead ribozyme: A proposed mechanism for RNA catalytic cleavage. Cell, (1995), 81, 991-1002. xxviiMcKay, Structure and function of the hammerhead ribozyme: an unfinished story. RNA, (1996), 2, 395-403. xxviiiLong, D., Uhlenbeck, O., Hertel, K. Ligation with hammerhead ribozymes. U.S. Pat. No. 5,633,133. xxixHertel, K. J., Herschlag, D., Uhlenbeck, O. A kinetic and thermodynamic framework for the hammerhead ribozyme reaction. Biochemistry, (1994) 33, 3374-3385. Beigelman, L., et aL, Chemical modifications of hammerhead ribozymes. J. Biol. Chem., (1995) 270, 25702-25708. xxxBeigelman, L., et al, Chemical modifications of hammerhead ribozymes. J. Biol. Chem., (1995) 270, 25702-25708. xxxiHampel, Arnold; Tritz, Richard; Hicks, Margaret; Cruz, Philip. ‘Hairpin’ catalytic RNA model: evidence for helixes and sequence requirement for substrate RNA. Nucleic Acids Res. (1990), 18(2), 299-304. xxxiiChownira, Bharat M.; Berzal-Herranz, Alfredo; Burke, John M., Novel guanosine requirement for catalysis by the hairpin ribozyme. Nature (London) (1991), 354(6351), 320-2. xxxiiiBerzal-Herranz, Alfredo; Joseph, Simpson; Chowrira, Bharat M.; Butcher, Samuel E.; Burke, John M., Essential nucleotide sequences and secondary structure elements of the hairpin ribozyme. EMBO J. (1993), 12(6), 2567-73. xxxivJoseph, Simpson; Berzal-Herranz, Alfredo; Chownira, Bharat M.; Butcher, Samuel E., Substrate selection rules for the hairpin ribozyme determined by in vitro selection, mutation, and analysis of mismatched substrates. Genes Dev. (1993), 7(1), 130-8. xxxvBerzal-Herranz, Alfredo; Joseph, Simpson; Burke, John M., In vitro selection of active hairpin ribozymes by sequential RNA-catalyzed cleavage and ligation reactions. Genes Dev. (1992), 6(1), 129-34. xxxviHegg, Lisa A.; Fedor, Martha J., Kinetics and Thermodynamics of Intermolecular Catalysis by Hairpin Ribozymes. Biochemistry (1995), 34(48), 15813-28. xxxviiGrasby, Jane A.; Mersmann, Karin; Singh, Mohinder; Gait, Michael J., Purine Functional Groups in Essential Residues of the Hairpin Ribozyme Required for Catalytic Cleavage of RNA. Biochemistry (1995), 34(12), 4068-76. xxxviiiSchmidt, Sabine; Beigelman, Leonid; Karpeisky, Alexander; Usman, Nassim; Sorensen, Ukik S.; Gait, Michael J., Base and sugar requirements for RNA cleavage of essential nucleoside residues in internal loop B of the hairpin ribozyme: implications for secondary structure. Nucleic Acids Res. (1996), 24(4), 573-81. xxxixPerrotta, Anne T.; Been, Michael D., Cleavage of oligoribonucleotides by a ribozyme derived from the hepatitis delta. virus RNA sequence. Biochemistry (1992), 31(1), 16-21. xlPerrotta, Anne T.; Been, Michael D., A pseudoknot-like structure required for efficient self-cleavage of hepatitis delta virus RNA. Nature (London) (1991), 350(6317), 434-6. xliPuttaraju, M.; Perrotta, Anne T.; Been, Michael D., A circular trans-acting hepatitis delta virus ribozyme. Nucleic Acids Res. (1993), 21(18), 4253-8.


[0189]

2










TABLE II













Wait
Wait
Wait



Equiva-

Time*
Time*
Time*


Reagent
lents
Amount
DNA
2′-O-methyl
RNA










A. 2.5 μmol Synthesis Cycle ABI 394 Instrument












Phosphoramidites
6.5
 163 μL
 45 sec
 2.5 min
 7.5 min


S-Ethyl Tetrazole
23.8
 238 μL
 45 sec
 2.5 min
 7.5 min


Acetic Anhydride
100
 233 μL
 5 sec
 5 sec
 5 sec


N-Methyl
186
 233 μL
 5 sec
 5 sec
 5 sec


Imidazole


TCA
176
 2.3 mL
 21 sec
 21 sec
 21 sec


Iodine
11.2
 1.7 mL
 45 sec
 45 sec
 45 sec


Beaucage
12.9
 645 μL
100 sec
300 sec
300 sec


Acetonitrile
NA
6.67 mL
NA
NA
NA







B. 0.2 μmol Synthesis Cycle ABI 394 Instrument












Phosphoramidites
15
  31 μL
 45 sec
233 sec
465 sec


S-Ethyl Tetrazole
38.7
  31 μL
 45 sec
233 min
465 sec


Acetic Anhydride
655
 124 μL
 5 sec
 5 sec
 5 sec


N-Methyl
1245
 124 μL
 5 sec
 5 sec
 5 sec


Imidazole


TCA
700
 732 μL
 10 sec
 10 sec
 10 sec


Iodine
20.6
 244 μL
 15 sec
 15 sec
 15 sec


Beaucage
7.7
 232 μL
100 sec
300 sec
300 sec


Acetonitrile
NA
2.64 mL
NA
NA
NA










C. 0.2 μmol Synthesis Cycle 96 well Instrument













Equiva-







lents
Amount

Wait



DNA/2′-
DNA/2′-
Wait
Time*
Wait



O-methyl/
O-methyl/
Time*
2′-O-
Time*


Reagent
Ribo
Ribo
DNA
methyl
Ribo





Phosphoramidites
22/33/66
40/60/
 60 sec
180 sec
360 sec




120 μL


S-Ethyl Tetrazole
70/105/
40/60/
 60 sec
180 min
360 sec



210
120 μL


Acetic Anhydride
265/265/
50/50/
 10 sec
 10 sec
 10 sec



265
50 μL


N-Methyl
502/502/
50/50/
 10 sec
 10 sec
 10 sec


Imidazole
502
 50 μL


TCA
238/475/
250/500/
 15 sec
 15 sec
 15 sec



475
500 μL


Iodine
6.8/6.8/
80/80/
 30 sec
 30 sec
 30 sec



6.8
80 μL


Beaucage
34/51/51
80/120/120
100 sec
200 sec
200 sec


Acetonitrile
NA
1150/1150/
NA
NA
NA




1150 μL






*Wait time does not include contact time during delivery.








[0190]

3





TABLE III










Human CLCA1 Hammerhead Ribozyme and Target Sequence 249.021















Rz




Seq ID

Seq ID


Pos
Substrate
No.
Ribozyme
No.














11
CUAAUGCU U UUGGUACA
1
UGUACCAA CUGAUGAG GCCGUUAGGC CGAA AGCAUUAG
2190





12
UAAUGCUU U UGGUACAA
2
UUGUACCA CUGAUGAG GCCGUUAGGC CGAA AAGCAUUA
2191





13
AAUGCUUU U GGUACAAA
3
UUUGUACC CUGAUGAG GCCGUUAGGC CGAA AAAGCAUU
2192





17
CUUUUGGU A CAAAUGGA
4
UCCAUUUG CUGAUGAG GCCGUUAGGC CGAA ACCAAAAG
2193





34
UGUGGAAU A UAAUUGAA
5
UUCAAUUA CUGAUGAG GCCGUUAGGC CGAA AUUCCACA
2194





36
UGGAAUAU A AUUGAAUA
6
UAUUCAAU CUGAUGAG GCCGUUAGGC CGAA AUAUUCCA
2195





39
AAUAUAAU U GAAUAUUU
7
AAAUAUUC CUGAUGAG GCCGUUAGGC CGAA AUUAUAUU
2196





44
AAUUGAAU A UUUUCUUG
8
CAAGAAAA CUGAUGAG GCCGUUAGGC CGAA AUUCAAUU
2197





46
UUGAAUAU U UUCUUGUU
9
AACAAGAA CUGAUGAG GCCGUUAGGC CGAA AUAUUCAA
2198





47
UGAAUAUU U UCUUGUUU
10
AAACAAGA CUGAUGAG GCCGUUAGGC CGAA AAUAUUCA
2199





48
GAAUAUUU U CUUGUUUA
11
UAAACAAG CUGAUGAG GCCGUUAGGC CGAA AAAUAUUC
2200





49
AAUAUUUU C UUGUUUAA
12
UUAAACAA CUGAUGAG GCCGUUAGGC CGAA AAAAUAUU
2201





51
UAUUUUCU U GUUUAAGG
13
CCUUAAAC CUGAUGAG GCCGUUAGGC CGAA AGAAAAUA
2202





54
UUUCUUGU U UAAGGGGA
14
UCCCCUUA CUGAUGAG GCCGUUAGGC CGAA ACAAGAAA
2203





55
UUCUUGUU U AAGGGGAG
15
CUCCCCUU CUGAUGAG GCCGUUAGGC CGAA AACAAGAA
2204





56
UCUUGUUU A AGGGGAGC
16
GCUCCCCU CUGAUGAG GCCGUUAGGC CGAA AAACAAGA
2205





77
AGAGGUGU U GAGGUUAU
17
AUAACCUC CUGAUGAG GCCGUUAGGC CGAA ACACCUCU
2206





83
GUUGAGGU U AUGUCAAG
18
CUUGACAU CUGAUGAG GCCGUUAGGC CGAA ACCUCAAC
2207





84
UUGAGGUU A UGUCAAGC
19
GCUUGACA CUGAUGAG GCCGUUAGGC CGAA AACCUCAA
2208





88
GGUUAUGU C AAGCAUCU
20
AGAUGCUU CUGAUGAG GCCGUUAGGC CGAA ACAUAACC
2209





95
UCAAGCAU C UGGCACAG
21
CUGUGCCA CUGAUGAG GCCGUUAGGC CGAA AUGCUUGA
2210





122
AUGGAAAU A UUUACAAG
22
CUUGUAAA CUGAUGAG GCCGUUAGGC CGAA AUUUCCAU
2211





124
GGAAAUAU U UACAAGUA
23
UACUUGUA CUGAUGAG GCCGUUAGGC CGAA AUAUUUCC
2212





125
GAAAUAUU U ACAAGUAC
24
GUACUUGU CUGAUGAG GCCGUUAGGC CGAA AAUAUUUC
2213





126
AAAUAUUU A CAAGUACG
25
CGUACUUG CUGAUGAG GCCGUUAGGC CGAA AAAUAUUU
2214





132
UUACAAGU A CGCAAUUU
26
AAAUUGCG CUGAUGAG GCCGUUAGGC CGAA ACUUGUAA
2215





139
UACGCAAU U UGAGACUA
27
UAGUCUCA CUGAUGAG GCCGUUAGGC CGAA AUUGCGUA
2216





140
ACGCAAUU U GAGACUAA
28
UUAGUCUC CUGAUGAG GCCGUUAGGC CGAA AAUUGCGU
2217





147
UUGAGACU A AGAUAUUG
29
CAAUAUCU CUGAUGAG GCCGUUAGGC CGAA AGUCUCAA
2218





152
ACUAAGAU A UUGUUAUC
30
GAUAACAA CUGAUGAG GCCGUUAGGC CGAA AUCUUAGU
2219





154
UAAGAUAU U GUUAUCAU
31
AUGAUAAC CUGAUGAG GCCGUUAGGC CGAA AUAUCUUA
2220





157
GAUAUUGU U AUCAUUCU
32
AGAAUGAU CUGAUGAG GCCGUUAGGC CGAA ACAAUAUC
2221





158
AUAUUGUU A UCAUUCUC
33
GAGAAUGA CUGAUGAG GCCGUUAGGC CGAA AACAAUAU
2222





160
AUUGUUAU C AUUCUCCU
34
AGGAGAAU CUGAUGAG GCCGUUAGGC CGAA AUAACAAU
2223





163
GUUAUCAU U CUCCUAUU
35
AAUAGGAG CUGAUGAG GCCGUUAGGC CGAA AUGAUAAC
2224





164
UUAUCAUU C UCCUAUUG
36
CAAUAGGA CUGAUGAG GCCGUUAGGC CGAA AAUGAUAA
2225





166
AUCAUUCU C CUAUUGAA
37
UUCAAUAG CUGAUGAG GCCGUUAGGC CGAA AGAAUGAU
2226





169
AUUCUCCU A UUGAAGAC
38
GUCUUCAA CUGAUGAG GCCGUUAGGC CGAA AGGAGAAU
2227





171
UCUCCUAU U GAAGACAA
39
UUGUCUUC CUGAUGAG GCCGUUAGGC CGAA AUAGGAGA
2228





187
AGAGCAAU A GUAAAACA
40
UGUUUUAC CUGAUGAG GCCGUUAGGC CGAA AUUGCUCU
2229





190
GCAAUAGU A AAACACAU
41
AUGUGUUU CUGAUGAG GCCGUUAGGC CGAA ACUAUUGC
2230





199
AAACACAU C AGGUCAGG
42
CCUGACCU CUGAUGAG GCCGUUAGGC CGAA AUGUGUUU
2231





204
CAUCAGGU C AGGGGGUU
43
AACCCCCU CUGAUGAG GCCGUUAGGC CGAA ACCUGAUG
2232





212
CAGGGGGU U AAAGACCU
44
AGGUCUUU CUGAUGAG GCCGUUAGGC CGAA ACCCCCUG
2233





213
AGGGGGUU A AAGACCUG
45
CAGGUCUU CUGAUGAG GCCGUUAGGC CGAA AACCCCCU
2234





226
CCUGUGAU A AACCACUU
46
AAGUGGUU CUGAUGAG GCCGUUAGGC CGAA AUCACAGG
2235





234
AAACCACU U CCGAUAAG
47
CUUAUCGG CUGAUGAG GCCGUUAGGC CGAA AGUGGUUU
2236





235
AACCACUU C CGAUAAGU
48
ACUUAUCG CUGAUGAG GCCGUUAGGC CGAA AAGUGGUU
2237





240
CUUCCGAU A AGUUGGAA
49
UUCCAACU CUGAUGAG GCCGUUAGGC CGAA AUCGGAAG
2238





244
CGAUAAGU U GGAAACGU
50
ACGUUUCC CUGAUGAG GCCGUUAGGC CGAA ACUUAUCG
2239





257
ACGUGUGU C UAUAUUUU
51
AAAAUAUA CUGAUGAG GCCGUUAGGC CGAA ACACACGU
2240





259
GUGUGUCU A UAUUUUCA
52
UGAAAAUA CUGAUGAG GCCGUUAGGC CGAA AGACACAC
2241





261
GUGUCUAU A UUUUCAUA
53
UAUGAAAA CUGAUGAG GCCGUUAGGC CGAA AUAGACAC
2242





263
GUCUAUAU U UUCAUAUC
54
GAUAUGAA CUGAUGAG GCCGUUAGGC CGAA AUAUAGAC
2243





264
UCUAUAUU U UCAUAUCU
55
AGAUAUGA CUGAUGAG GCCGUUAGGC CGAA AAUAUAGA
2244





265
CUAUAUUU U CAUAUCUG
56
CAGAUAUG CUGAUGAG GCCGUUAGGC CGAA AAAUAUAG
2245





266
UAUAUUUU C AUAUCUGU
57
ACAGAUAU CUGAUGAG GCCGUUAGGC CGAA AAAAUAUA
2246





269
AUUUUCAU A UCUGUAUA
58
UAUACAGA CUGAUGAG GCCGUUAGGC CGAA AUGAAAAU
2247





271
UUUCAUAU C UGUAUAUA
59
UAUAUACA CUGAUGAG GCCGUUAGGC CGAA AUAUGAAA
2248





275
AUAUCUGU A UAUAUAUA
60
UAUAUAUA CUGAUGAG GCCGUUAGGC CGAA ACAGAUAU
2249





277
AUCUGUAU A UAUAUAAU
61
AUUAUAUA CUGAUGAG GCCGUUAGGC CGAA AUACAGAU
2250





279
CUGUAUAU A UAUAAUGG
62
CCAUUAUA CUGAUGAG GCCGUUAGGC CGAA AUAUACAG
2251





281
GUAUAUAU A UAAUGGUA
63
UACCAUUA CUGAUGAG GCCGUUAGGC CGAA AUAUAUAC
2252





283
AUAUAUAU A AUGGUAAA
64
UUUACCAU CUGAUGAG GCCGUUAGGC CGAA AUAUAUAU
2253





289
AUAAUGGU A AAGAAAGA
65
UCUUUCUU CUGAUGAG GCCGUUAGGC CGAA ACCAUUAU
2254





303
AGACACCU U CGUAACCC
66
GGGUUACG CUGAUGAG GCCGUUAGGC CGAA AGGUGUCU
2255





304
GACACCUU C GUAACCCG
67
CGGGUUAC CUGAUGAG GCCGUUAGGC CGAA AAGGUGUC
2256





307
ACCUUCGU A ACCCGCAU
68
AUGCGGGU CUGAUGAG GCCGUUAGGC CGAA ACGAAGGU
2257





326
ACCCGCAU U UUCCAAAG
69
CUUUGGAA CUGAUGAG GCCGUUAGGC CGAA AUGCGGGU
2258





317
CCCGCAUU U UCCAAAGA
70
UCUUUGGA CUGAUGAG GCCGUUAGGC CGAA AAUGCGGG
2259





318
CCGCAUUU U CCAAAGAG
71
CUCUUUGG CUGAUGAG GCCGUUAGGC CGAA AAAUGCGG
2260





319
CGCAUUUU C CAAAGAGA
72
UCUCUUUG CUGAUGAG GCCGUUAGGC CGAA AAAAUGCG
2261





333
AGAGGAAU C ACAGGGAG
73
CUCCCUGU CUGAUGAG GCCGUUAGGC CGAA AUUCCUCU
2262





346
GGAGAUGU A CAGCAAUG
74
CAUUGCUG CUGAUGAG GCCGUUAGGC CGAA ACAUCUCC
2263





362
GGGGCCAU U UAAGAGUU
75
AACUCUUA CUGAUGAG GCCGUUAGGC CGAA AUGGCCCC
2264





363
GGGCCAUU U AAGAGUUC
76
GAACUCUU CUGAUGAG GCCGUUAGGC CGAA AAUGGCCC
2265





364
GGCCAUUU A AGAGUUCU
77
AGAACUCU CUGAUGAG GCCGUUAGGC CGAA AAAUGGCC
2266





370
UUAAGAGU U CUGUGUUC
78
GAACACAG CUGAUGAG GCCGUUAGGC CGAA ACUCUUAA
2267





371
UAAGAGUU C UGUGUUCA
79
UGAACACA CUGAUGAG GCCGUUAGGC CGAA AACUCUUA
2268





377
UUCUGUGU U CAUCUUGA
80
UCAAGAUG CUGAUGAG GCCGUUAGGC CGAA ACACAGAA
2269





378
UCUGUGUU C AUCUUGAU
81
AUCAAGAU CUGAUGAG GCCGUUAGGC CGAA AACACAGA
2270





381
GUGUUCAU C UUGAUUCU
82
AGAAUCAA CUGAUGAG GCCGUUAGGC CGAA AUGAACAC
2271





383
GUUCAUCU U GAUUCUUC
83
GAAGAAUC CUGAUGAG GCCGUUAGGC CGAA AGAUGAAC
2272





387
AUCUUGAU U CUUCACCU
84
AGGUGAAG CUGAUGAG GCCGUUAGGC CGAA AUCAAGAU
2273





388
UCUUGAUU C UUCACCUU
85
AAGGUGAA CUGAUGAG GCCGUUAGGC CGAA AAUCAAGA
2274





390
UUGAUUCU U CACCUUCU
86
AGAAGGUG CUGAUGAG GCCGUUAGGC CGAA AGAAUCAA
2275





391
UGAUUCUU C ACCUUCUA
87
UAGAAGGU CUGAUGAG GCCGUUAGGC CGAA AAGAAUCA
2276





396
CUUCACCU U CUAGAAGG
88
CCUUCUAG CUGAUGAG GCCGUUAGGC CGAA AGGUGAAG
2277





397
UUCACCUU C UAGAAGGG
89
CCCUUCUA CUGAUGAG GCCGUUAGGC CGAA AAGGUGAA
2278





399
CACCUUCU A GAAGGGGC
90
GCCCCUUC CUGAUGAG GCCGUUAGGC CGAA AGAAGGUG
2279





415
CCCUGAGU A AUUCACUC
91
GAGUGAAU CUGAUGAG GCCGUUAGGC CGAA ACUCAGGG
2280





418
UGAGUAAU U CACUCAUU
92
AAUGAGUG CUGAUGAG GCCGUUAGGC CGAA AUUACUCA
2281





419
GAGUAAUU C ACUCAUUC
93
GAAUGAGU CUGAUGAG GCCGUUAGGC CGAA AAUUACUC
2282





423
AAUUCACU C AUUCAGCU
94
AGCUGAAU CUGAUGAG GCCGUUAGGC CGAA AGUGAAUU
2283





426
UCACUCAU U CAGCUGAA
95
UUCAGCUG CUGAUGAG GCCGUUAGGC CGAA AUGAGUGA
2284





427
CACUCAUU C AGCUGAAC
96
GUUCAGCU CUGAUGAG GCCGUUAGGC CGAA AAUGAGUG
2285





446
CAAUGGCU A UGAAGGCA
97
UGCCUUCA CUGAUGAG GCCGUUAGGC CGAA AGCCAUUG
2286





456
GAAGGCAU U GUCGUUGC
98
GCAACGAC CUGAUGAG GCCGUUAGGC CGAA AUGCCUUC
2287





459
GGCAUUGU C GUUGCAAU
99
AUUGCAAC CUGAUGAG GCCGUUAGGC CGAA ACAAUGCC
2288





462
AUUGUCGU U GCAAUCGA
100
UCGAUUGC CUGAUGAG GCCGUUAGGC CGAA ACGACAAU
2289





468
GUUGCAAU C GACCCCAA
101
UUGGGGUC CUGAUGAG GCCGUUAGGC CGAA AUUGCAAC
2290





498
GAAACACU C AUUCAACA
102
UGUUGAAU CUGAUGAG GCCGUUAGGC CGAA AGUGUUUC
2291





501
ACACUCAU U CAACAAAU
103
AUUUGUUG CUGAUGAG GCCGUUAGGC CGAA AUGAGUGU
2292





502
CACUCAUU C AACAAAUA
104
UAUUUGUU CUGAUGAG GCCGUUAGGC CGAA AAUGAGUG
2293





510
CAACAAAU A AAGGACAU
105
AUGUCCUU CUGAUGAG GCCGUUAGGC CGAA AUUUGUUG
2294





533
CCAGGCAU C UCUGUAUC
106
GAUACAGA CUGAUGAG GCCGUUAGGC CGAA AUGCCUGG
2295





535
AGGCAUCU C UGUAUCUG
107
CAGAUACA CUGAUGAG GCCGUUAGGC CGAA AGAUGCCU
2296





539
AUCUCUGU A UCUGUUUG
108
CAAACAGA CUGAUGAG GCCGUUAGGC CGAA ACAGAGAU
2297





541
CUCUGUAU C UGUUUGAA
109
UUCAAACA CUGAUGAG GCCGUUAGGC CGAA AUACAGAG
2298





545
GUAUCUGU U UGAAGCUA
110
UAGCUUCA CUGAUGAG GCCGUUAGGC CGAA ACAGAUAC
2299





546
UAUCUGUU U GAAGCUAC
111
GUAGCUUC CUGAUGAG GCCGUUAGGC CGAA AACAGAUA
2300





553
UUGAAGCU A CAGGAAAG
112
CUUUCCUG CUGAUGAG GCCGUUAGGC CGAA AGCUUCAA
2301





566
AAAGCGAU U UUAUUUCA
113
UGAAAUAA CUGAUGAG GCCGUUAGGC CGAA AUCGCUUU
2302





567
AAGCGAUU U UAUUUCAA
114
UUGAAAUA CUGAUGAG GCCGUUAGGC CGAA AAUCGCUU
2303





568
AGCGAUUU U AUUUCAAA
115
UUUGAAAU CUGAUGAG GCCGUUAGGC CGAA AAAUCGCU
2304





569
GCGAUUUU A UUUCAAAA
116
UUUUGAAA CUGAUGAG GCCGUUAGGC CGAA AAAAUCGC
2305





571
GAUUUUAU U UCAAAAAU
117
AUUUUUGA CUGAUGAG GCCGUUAGGC CGAA AUAAAAUC
2306





572
AUUUUAUU U CAAAAAUG
118
CAUUUUUG CUGAUGAG GCCGUUAGGC CGAA AAUAAAAU
2307





573
UUUUAUUU C AAAAAUGU
119
ACAUUUUU CUGAUGAG GCCGUUAGGC CGAA AAAUAAAA
2308





582
AAAAAUGU U GCCAUUUU
120
AAAAUGGC CUGAUGAG GCCGUUAGGC CGAA ACAUUUUU
2309





588
GUUGCCAU U UUGAUUCC
121
GGAAUCAA CUGAUGAG GCCGUUAGGC CGAA AUGGCAAC
2310





589
UUGCCAUU U UGAUUCCU
122
AGGAAUCA CUGAUGAG GCCGUUAGGC CGAA AAUGGCAA
2311





590
UGCCAUUU U GAUUCCUG
123
CAGGAAUC CUGAUGAG GCCGUUAGGC CGAA AAAUGGCA
2312





594
AUUUUGAU U CCUGAAAC
124
GUUUCAGG CUGAUGAG GCCGUUAGGC CGAA AUCAAAAU
2313





595
UUUUGAUU C CUGAAACA
125
UGUUUCAG CUGAUGAG GCCGUUAGGC CGAA AAUCAAAA
2314





623
GGCUGACU A UGUGAGAC
126
GUCUCACA CUGAUGAG GCCGUUAGGC CGAA AGUCAGCC
2315





639
CCAAAACU U GAGACCUA
127
UAGGUCUC CUGAUGAG GCCGUUAGGC CGAA AGUUUUGG
2316





647
UGAGACCU A CAAAAAUG
128
CAUUUUUG CUGAUGAG GCCGUUAGGC CGAA AGGUCUCA
2317





663
GCUGAUGU U CUGGUUGC
129
GCAACCAG CUGAUGAG GCCGUUAGGC CGAA ACAUCAGC
2318





664
CUGAUGUU C UGGUUGCU
130
AGCAACCA CUGAUGAG GCCGUUAGGC CGAA AACAUCAG
2319





669
GUUCUGGU U GCUGAGUC
131
GACUCAGC CUGAUGAG GCCGUUAGGC CGAA ACCAGAAC
2320





677
UGCUGAGU C UACUCCUC
132
GAGGAGUA CUGAUGAG GCCGUUAGGC CGAA ACUCAGCA
2321





679
CUGAGUCU A CUCCUCCA
133
UGGAGGAG CUGAUGAG GCCGUUAGGC CGAA AGACUCAG
2322





682
AGUCUACU C CUCCAGGU
134
ACCUGGAG CUGAUGAG GCCGUUAGGC CGAA AGUAGACU
2323





685
CUACUCCU C CAGGUAAU
135
AUUACCUG CUGAUGAG GCCGUUAGGC CGAA AGGAGUAG
2324





691
CUCCAGGU A AUGAUGAA
136
UUCAUCAU CUGAUGAG GCCGUUAGGC CGAA ACCUGGAG
2325





704
UGAACCCU A CACUGAGC
137
GCUCAGUG CUGAUGAG GCCGUUAGGC CGAA AGGGUUCA
2326





747
GAAAGGAU C CACCUCAC
138
GUGAGGUG CUGAUGAG GCCGUUAGGC CGAA AUCCUUUC
2327





753
AUCCACCU C ACUCCUGA
139
UCAGGAGU CUGAUGAG GCCGUUAGGC CGAA AGGUGGAU
2328





757
ACCUCACU C CUGAUUUC
140
GAAAUCAG CUGAUGAG GCCGUUAGGC CGAA AGUGAGGU
2329





763
CUCCUGAU U UCAUUGCA
141
UGCAAUGA CUGAUGAG GCCGUUAGGC CGAA AUCAGGAG
2330





764
UCCUGAUU U CAUUGCAG
142
CUGCAAUG CUGAUGAG GCCGUUAGGC CGAA AAUCAGGA
2331





765
CCUGAUUU C AUUGCAGG
143
CCUGCAAU CUGAUGAG GCCGUUAGGC CGAA AAAUCAGG
2332





768
GAUUUCAU U GCAGGAAA
144
UUUCCUGC CUGAUGAG GCCGUUAGGC CGAA AUGAAAUC
2333





782
AAAAAAGU U AGCUGAAU
145
AUUCAGCU CUGAUGAG GCCGUUAGGC CGAA ACUUUUUU
2334





783
AAAAAGUU A GCUGAAUA
146
UAUUCAGC CUGAUGAG GCCGUUAGGC CGAA AACUUUUU
2335





791
AGCUGAAU A UGGACCAC
147
GUGGUCCA CUGAUGAG GCCGUUAGGC CGAA AUUCAGCU
2336





805
CACAAGGU A AGGCAUUU
148
AAAUGCCU CUGAUGAG GCCGUUAGGC CGAA ACCUUGUG
2337





812
UAAGGCAU U UGUCCAUG
149
CAUGGACA CUGAUGAG GCCGUUAGGC CGAA AUGCCUUA
2338





813
AAGGCAUU U GUCCAUGA
150
UCAUGGAC CUGAUGAG GCCGUUAGGC CGAA AAUGCCUU
2339





816
GCAUUUGU C CAUGAGUG
151
CACUCAUG CUGAUGAG GCCGUUAGGC CGAA ACAAAUGC
2340





829
AGUGGGCU C AUCUACGA
152
UCGUAGAU CUGAUGAG GCCGUUAGGC CGAA AGCCCACU
2341





832
GGGCUCAU C UACGAUGG
153
CCAUCGUA CUGAUGAG GCCGUUAGGC CGAA AUGAGCCC
2342





834
GCUCAUCU A CGAUGGGG
154
CCCCAUCG CUGAUGAG GCCGUUAGGC CGAA AGAUGAGC
2343





846
UGGGGAGU A UUUGACGA
155
UCGUCAAA CUGAUGAG GCCGUUAGGC CGAA ACUCCCCA
2344





848
GGGAGUAU U UGACGAGU
156
ACUCGUCA CUGAUGAG GCCGUUAGGC CGAA AUACUCCC
2345





849
GGAGUAUU U GACGAGUA
157
UACUCGUC CUGAUGAG GCCGUUAGGC CGAA AAUACUCC
2346





857
UGACGAGU A CAAUAAUG
158
CAUUAUUG CUGAUGAG GCCGUUAGGC CGAA ACUCGUCA
2347





862
AGUACAAU A AUGAUGAG
159
CUCAUCAU CUGAUGAG GCCGUUAGGC CGAA AUUGUACU
2348





875
UGAGAAAU U CUACUUAU
160
AUAAGUAG CUGAUGAG GCCGUUAGGC CGAA AUUUCUCA
2349





876
GAGAAAUU C UACUUAUC
161
GAUAAGUA CUGAUGAG GCCGUUAGGC CGAA AAUUUCUC
2350





878
GAAAUUCU A CUUAUCCA
162
UGGAUAAG CUGAUGAG GCCGUUAGGC CGAA AGAAUUUC
2351





881
AUUCUACU U AUCCAAUG
163
CAUUGGAU CUGAUGAG GCCGUUAGGC CGAA AGUAGAAU
2352





882
UUCUACUU A UCCAAUGG
164
CCAUUGGA CUGAUGAG GCCGUUAGGC CGAA AAGUAGAA
2353





884
CUACUUAU C CAAUGGAA
165
UUCCAUUG CUGAUGAG GCCGUUAGGC CGAA AUAAGUAG
2354





897
GGAAGAAU A CAAGCAGU
166
ACUGCUUG CUGAUGAG GCCGUUAGGC CGAA AUUCUUCC
2355





906
CAAGCAGU A AGAUGUUC
167
GAACAUCU CUGAUGAG GCCGUUAGGC CGAA ACUGCUUG
2356





913
UAAGAUGU U CAGCAGGU
168
ACCUGCUG CUGAUGAG GCCGUUAGGC CGAA ACAUCUUA
2357





914
AAGAUGUU C AGCAGGUA
169
UACCUGCU CUGAUGAG GCCGUUAGGC CGAA AACAUCUU
2358





922
CAGCAGGU A UUACUGGU
170
ACCAGUAA CUGAUGAG GCCGUUAGGC CGAA ACCUGCUG
2359





924
GCAGGUAU U ACUGGUAC
171
GUACCAGU CUGAUGAG GCCGUUAGGC CGAA AUACCUGC
2360





925
CAGGUAUU A CUGGUACA
172
UGUACCAG CUGAUGAG GCCGUUAGGC CGAA AAUACCUG
2361





931
UUACUGGU A CAAAUGUA
173
UACAUUUG CUGAUGAG GCCGUUAGGC CGAA ACCAGUAA
2362





939
ACAAAUGU A GUAAAGAA
174
UUCUUUAC CUGAUGAG GCCGUUAGGC CGAA ACAUUUGU
2363





942
AAUGUAGU A AAGAAGUG
175
CACUUCUU CUGAUGAG GCCGUUAGGC CGAA ACUACAUU
2364





952
AGAAGUGU C AGGGAGGC
176
GCCUCCCU CUGAUGAG GCCGUUAGGC CGAA ACACUUCU
2365





967
GCAGCUGU U ACACCAAA
177
UUUGGUGU CUGAUGAG GCCGUUAGGC CGAA ACAGCUGC
2366





968
CAGCUGUU A CACCAAAA
178
UUUUGGUG CUGAUGAG GCCGUUAGGC CGAA AACAGCUG
2367





986
AUGCACAU U CAAUAAAG
179
CUUUAUUG CUGAUGAG GCCGUUAGGC CGAA AUGUGCAU
2368





987
UGCACAUU C AAUAAAGU
180
ACUUUAUU CUGAUGAG GCCGUUAGGC CGAA AAUGUGCA
2369





991
CAUUCAAU A AAGUUACA
181
UGUAACUU CUGAUGAG GCCGUUAGGC CGAA AUUGAAUG
2370





996
AAUAAAGU U ACAGGACU
182
AGUCCUGU CUGAUGAG GCCGUUAGGC CGAA ACUUUAUU
2371





997
AUAAAGUU A CAGGACUC
183
GAGUCCUG CUGAUGAG GCCGUUAGGC CGAA AACUUUAU
2372





1005
ACAGGACU C UAUGAAAA
184
UUUUCAUA CUGAUGAG GCCGUUAGGC CGAA AGUCCUGU
2373





1007
AGGACUCU A UGAAAAAG
185
CUUUUUCA CUGAUGAG GCCGUUAGGC CGAA AGAGUCCU
2374





1025
AUGUGAGU U UGUUCUCC
186
GGAGAACA CUGAUGAG GCCGUUAGGC CGAA ACUCACAU
2375





1026
UGUGAGUU U GUUCUCCA
187
UGGAGAAC CUGAUGAG GCCGUUAGGC CGAA AACUCACA
2376





1029
GAGUUUGU U CUCCAAUC
188
GAUUGGAG CUGAUGAG GCCGUUAGGC CGAA ACAAACUC
2377





1030
AGUUUGUU C UCCAAUCC
189
GGAUUGGA CUGAUGAG GCCGUUAGGC CGAA AACAAACU
2378





1032
UUUGUUCU C CAAUCCCG
190
CGGGAUUG CUGAUGAG GCCGUUAGGC CGAA AGAACAAA
2379





1037
UCUCCAAU C CCGCCAGA
191
UCUGGCGG CUGAUGAG GCCGUUAGGC CGAA AUUGGAGA
2380





1057
AGAAGGCU U CUAUAAUG
192
CAUUAUAG CUGAUGAG GCCGUUAGGC CGAA AGCCUUCU
2381





1058
GAAGGCUU C UAUAAUGU
193
ACAUUAUA CUGAUGAG GCCGUUAGGC CGAA AAGCCUUC
2382





1060
AGGCUUCU A UAAUGUUU
194
AAACAUUA CUGAUGAG GCCGUUAGGC CGAA AGAAGCCU
2383





1062
GCUUCUAU A AUGUUUGC
195
GCAAACAU CUGAUGAG GCCGUUAGGC CGAA AUAGAAGC
2384





1067
UAUAAUGU U UGCACAAC
196
GUUGUGCA CUGAUGAG GCCGUUAGGC CGAA ACAUUAUA
2385





1068
AUAAUGUU U GCACAACA
197
UGUUGUGC CUGAUGAG GCCGUUAGGC CGAA AACAUUAU
2386





1080
CAACAUGU U GAUUCUAU
198
AUAGAAUC CUGAUGAG GCCGUUAGGC CGAA ACAUGUUG
2387





1084
AUGUUGAU U CUAUAGUU
199
AACUAUAG CUGAUGAG GCCGUUAGGC CGAA AUCAACAU
2388





1085
UGUUGAUU C UAUAGUUG
200
CAACUAUA CUGAUGAG GCCGUUAGGC CGAA AAUCAACA
2389





1087
UUGAUUCU A UAGUUGAA
201
UUCAACUA CUGAUGAG GCCGUUAGGC CGAA AGAAUCAA
2390





1089
GAUUCUAU A GUUGAAUU
202
AAUUCAAC CUGAUGAG GCCGUUAGGC CGAA AUAGAAUC
2391





1092
UCUAUAGU U GAAUUCUG
203
CAGAAUUC CUGAUGAG GCCGUUAGGC CGAA ACUAUAGA
2392





1097
AGUUGAAU U CUGUACAG
204
CUGUACAG CUGAUGAG GCCGUUAGGC CGAA AUUCAACU
2393





1098
GUUGAAUU C UGUACAGA
205
UCUGUACA CUGAUGAG GCCGUUAGGC CGAA AAUUCAAC
2394





1102
AAUUCUGU A CAGAACAA
206
UUGUUCUG CUGAUGAG GCCGUUAGGC CGAA ACAGAAUU
2395





1129
AAGAAGCU C CAAACAAG
207
CUUGUUUG CUGAUGAG GCCGUUAGGC CGAA AGCUUCUU
2396





1144
AGCAAAAU C AAAAAUGC
208
GCAUUUUU CUGAUGAG GCCGUUAGGC CGAA AUUUUGCU
2397





1156
AAUGCAAU C UCCGAAGC
209
GCUUCGGA CUGAUGAG GCCGUUAGGC CGAA AUUGCAUU
2398





1158
UGCAAUCU C CGAAGCAC
210
GUGCUUCG CUGAUGAG GCCGUUAGGC CGAA AGAUUGCA
2399





1179
GAAGUGAU C CGUGAUUC
211
GAAUCACG CUGAUGAG GCCGUUAGGC CGAA AUCACUUC
2400





1186
UCCGUGAU U CUGAGGAC
212
GUCCUCAG CUGAUGAG GCCGUUAGGC CGAA AUCACGGA
2401





1187
CCGUGAUU C UGAGGACU
213
AGUCCUCA CUGAUGAG GCCGUUAGGC CGAA AAUCACGG
2402





1196
UGAGGACU U UAAGAAAA
214
UUUUCUUA CUGAUGAG GCCGUUAGGC CGAA AGUCCUCA
2403





1197
GAGGACUU U AAGAAAAC
215
GUUUUCUU CUGAUGAG GCCGUUAGGC CGAA AAGUCCUC
2404





1198
AGGACUUU A AGAAAACC
216
GGUUUUCU CUGAUGAG GCCGUUAGGC CGAA AAAGUCCU
2405





1210
AAACCACU C CUAUGACA
217
UGUCAUAG CUGAUGAG GCCGUUAGGC CGAA AGUGGUUU
2406





1213
CCACUCCU A UGACAACA
218
UGUUGUCA CUGAUGAG GCCGUUAGGC CGAA AGGAGUGG
2407





1234
CACCAAAU C CCACCUUC
219
GAAGGUGG CUGAUGAG GCCGUUAGGC CGAA AUUUGGUG
2408





1241
UCCCACCU U CUCAUUGC
220
GCAAUGAG CUGAUGAG GCCGUUAGGC CGAA AGGUGGGA
2409





1242
CCCACCUU C UCAUUGCU
221
AGCAAUGA CUGAUGAG GCCGUUAGGC CGAA AAGGUGGG
2410





1244
CACCUUCU C AUUGCUGC
222
GCAGCAAU CUGAUGAG GCCGUUAGGC CGAA AGAAGGUG
2411





1247
CUUCUCAU U GCUGCAGA
223
UCUGCAGC CUGAUGAG GCCGUUAGGC CGAA AUGAGAAG
2412





1257
CUGCAGAU U GGACAAAG
224
CUUUGUCC CUGAUGAG GCCGUUAGGC CGAA AUCUGCAG
2413





1269
CAAAGAAU U GUGUGUUU
225
AAACACAC CUGAUGAG GCCGUUAGGC CGAA AUUCUUUG
2414





1276
UUGUGUGU U UAGUCCUU
226
AAGGACUA CUGAUGAG GCCGUUAGGC CGAA ACACACAA
2415





1277
UGUGUGUU U AGUCCUUG
227
CAAGGACU CUGAUGAG GCCGUUAGGC CGAA AACACACA
2416





1278
GUGUGUUU A GUCCUUGA
228
UCAAGGAC CUGAUGAG GCCGUUAGGC CGAA AAACACAC
2417





1281
UGUUUAGU C CUUGACAA
229
UUGUCAAG CUGAUGAG GCCGUUAGGC CGAA ACUAAACA
2418





1284
UUAGUCCU U GACAAAUC
230
GAUUUGUC CUGAUGAG GCCGUUAGGC CGAA AGGACUAA
2419





1292
UGACAAAU C UGGAAGCA
231
UGCUUCCA CUGAUGAG GCCGUUAGGC CGAA AUUUGUCA
2420





1312
CGACUGGU A ACCGCCUC
232
GAGGCGGU CUGAUGAG GCCGUUAGGC CGAA ACCAGUCG
2421





1320
AACCGCCU C AAUCGACU
233
AGUCGAUU CUGAUGAG GCCGUUAGGC CGAA AGGCGGUU
2422





1324
GCCUCAAU C GACUGAAU
234
AUUCAGUC CUGAUGAG GCCGUUAGGC CGAA AUUGAGGC
2423





1333
GACUGAAU C AAGCAGGC
235
GCCUGCUU CUGAUGAG GCCGUUAGGC CGAA AUUCAGUC
2424





1347
GGCCAGCU U UUCCUGCU
236
AGCAGGAA CUGAUGAG GCCGUUAGGC CGAA AGCUGGCC
2425





1348
GCCAGCUU U UCCUGCUG
237
CAGCAGGA CUGAUGAG GCCGUUAGGC CGAA AAGCUGGC
2426





1349
CCAGCUUU U CCUGCUGC
238
GCAGCAGG CUGAUGAG GCCGUUAGGC CGAA AAAGCUGG
2427





1350
CAGCUUUU C CUGCUGCA
239
UGCAGCAG CUGAUGAG GCCGUUAGGC CGAA AAAAGCUG
2428





1365
CAGACAGU U GAGCUGGG
240
CCCAGCUC CUGAUGAG GCCGUUAGGC CGAA ACUGUCUG
2429





1376
GCUGGGGU C CUGGGUUG
241
CAACCCAG CUGAUGAG GCCGUUAGGC CGAA ACCCCAGC
2430





1383
UCCUGGGU U GGGAUGGU
242
ACCAUCCC CUGAUGAG GCCGUUAGGC CGAA ACCCAGGA
2431





1397
GGUGACAU U UGACAGUG
243
CACUGUCA CUGAUGAG GCCGUUAGGC CGAA AUGUCACC
2432





1398
GUGACAUU U GACAGUGC
244
GCACUGUC CUGAUGAG GCCGUUAGGC CGAA AAUGUCAC
2433





1416
GCCCAUGU A CAAAGUGA
245
UCACUUUG CUGAUGAG GCCGUUAGGC CGAA ACAUGGGC
2434





1428
AGUGAACU C AUACAGAU
246
AUCUGUAU CUGAUGAG GCCGUUAGGC CGAA AGUUCACU
2435





1431
GAACUCAU A CAGAUAAA
247
UUUAUCUG CUGAUGAG GCCGUUAGGC CGAA AUGAGUUC
2436





1437
AUACAGAU A AACAGUGG
248
CCACUGUU CUGAUGAG GCCGUUAGGC CGAA AUCUGUAU
2437





1464
GACACACU C GCCAAAAG
249
CUUUUGGC CUGAUGAG GCCGUUAGGC CGAA AGUGUGUC
2438





1475
CAAAAGAU U ACCUGCAG
250
CUGCAGGU CUGAUGAG GCCGUUAGGC CGAA AUCUUUUG
2439





1476
AAAAGAUU A CCUGCAGC
251
GCUGCAGG CUGAUGAG GCCGUUAGGC CGAA AAUCUUUU
2440





1489
CAGCAGCU U CAGGAGGG
252
CCCUCCUG CUGAUGAG GCCGUUAGGC CGAA AGCUGCUG
2441





1490
AGCAGCUU C AGGAGGGA
253
UCCCUCCU CUGAUGAG GCCGUUAGGC CGAA AAGCUGCU
2442





1502
AGGGACGU C CAUCUGCA
254
UGCAGAUG CUGAUGAG GCCGUUAGGC CGAA ACGUCCCU
2443





1506
ACGUCCAU C UGCAGCGG
255
CCGCUGCA CUGAUGAG GCCGUUAGGC CGAA AUGGACGU
2444





1518
AGCGGGCU U CGAUCGGC
256
GCCGAUCG CUGAUGAG GCCGUUAGGC CGAA AGCCCGCU
2445





1519
GCGGGCUU C GAUCGGCA
257
UGCCGAUC CUGAUGAG GCCGUUAGGC CGAA AAGCCCGC
2446





1523
GCUUCGAU C GGCAUUUA
258
UAAAUGCC CUGAUGAG GCCGUUAGGC CGAA AUCGAAGC
2447





1529
AUCGGCAU U UACUGUGA
259
UCACAGUA CUGAUGAG GCCGUUAGGC CGAA AUGCCGAU
2448





1530
UCGGCAUU U ACUGUGAU
260
AUCACAGU CUGAUGAG GCCGUUAGGC CGAA AAUGCCGA
2449





1531
CGGCAUUU A CUGUGAUU
261
AAUCACAG CUGAUGAG GCCGUUAGGC CGAA AAAUGCCG
2450





1539
ACUGUGAU U AGGAAGAA
262
UUCUUCCU CUGAUGAG GCCGUUAGGC CGAA AUCACAGU
2451





1540
CUGUGAUU A GGAAGAAA
263
UUUCUUCC CUGAUGAG GCCGUUAGGC CGAA AAUCACAG
2452





1550
GAAGAAAU A UCCAACUG
264
CAGUUGGA CUGAUGAG GCCGUUAGGC CGAA AUUUCUUC
2453





1552
AGAAAUAU C CAACUGAU
265
AUCAGUUG CUGAUGAG GCCGUUAGGC CGAA AUAUUUCU
2454





1565
UGAUGGAU C UGAAAUUG
266
CAAUUUCA CUGAUGAG GCCGUUAGGC CGAA AUCCAUCA
2455





1572
UCUGAAAU U GUGCUGCU
267
AGCAGCAC CUGAUGAG GCCGUUAGGC CGAA AUUUCAGA
2456





1603
ACAACACU A UAAGUGGG
268
CCCACUUA CUGAUGAG GCCGUUAGGC CGAA AGUGUUGU
2457





1605
AACACUAU A AGUGGGUG
269
CACCCACU CUGAUGAG GCCGUUAGGC CGAA AUAGUGUU
2458





1616
UGGGUGCU U UAACGAGG
270
CCUCGUUA CUGAUGAG GCCGUUAGGC CGAA AGCACCCA
2459





1617
GGGUGCUU U AACGAGGU
271
ACCUCGUU CUGAUGAG GCCGUUAGGC CGAA AAGCACCC
2460





1618
GGUGCUUU A ACGAGGUC
272
GACCUCGU CUGAUGAG GCCGUUAGGC CGAA AAAGCACC
2461





1626
AACGAGGU C AAACAAAG
273
CUUUGUUU CUGAUGAG GCCGUUAGGC CGAA ACCUCGUU
2462





1644
GGUGCCAU C AUCCACAC
274
GUGUGGAU CUGAUGAG GCCGUUAGGC CGAA AUGGCACC
2463





1647
GCCAUCAU C CACACAGU
275
ACUGUGUG CUGAUGAG GCCGUUAGGC CGAA AUGAUGGC
2464





1656
CACACAGU C GCUUUGGG
276
CCCAAAGC CUGAUGAG GCCGUUAGGC CGAA ACUGUGUG
2465
2465





1660
CAGUCGCU U UGGGGCCC
277
GGGCCCCA CUGAUGAG GCCGUUAGGC CGAA AGCGACUG
2466





1661
AGUCGCUU U GGGGCCCU
278
AGGGCCCC CUGAUGAG GCCGUUAGGC CGAA AAGCGACU
2467





1670
GGGGCCCU C UGCAGCUC
279
GAGCUGCA CUGAUGAG GCCGUUAGGC CGAA AGGGCCCC
2468





1678
CUGCAGCU C AAGAACUA
280
UAGUUCUU CUGAUGAG GCCGUUAGGC CGAA AGCUGCAG
2469





1686
CAAGAACU A GAGGAGCU
281
AGCUCCUC CUGAUGAG GCCGUUAGGC CGAA AGUUCUUG
2470





1697
GGAGCUGU C CAAAAUGA
282
UCAUUUUG CUGAUGAG GCCGUUAGGC CGAA ACAGCUCC
2471





1714
CAGGAGGU U UACAGACA
283
UGUCUGUA CUGAUGAG GCCGUUAGGC CGAA ACCUCCUG
2472





1715
AGGAGGUU U ACAGACAU
284
AUGUCUGU CUGAUGAG GCCGUUAGGC CGAA AACCUCCU
2473





1716
GGAGGUUU A CAGACAUA
285
UAUGUCUG CUGAUGAG GCCGUUAGGC CGAA AAACCUCC
2474





1724
ACAGACAU A UGCUUCAG
286
CUGAAGCA CUGAUGAG GCCGUUAGGC CGAA AUGUCUGU
2475





1729
CAUAUGCU U CAGAUCAA
287
UUGAUCUG CUGAUGAG GCCGUUAGGC CGAA AGCAUAUG
2476





1730
AUAUGCUU C AGAUCAAG
288
CUUGAUCU CUGAUGAG GCCGUUAGGC CGAA AAGCAUAU
2477





1735
CUUCAGAU C AAGUUCAG
289
CUGAACUU CUGAUGAG GCCGUUAGGC CGAA AUCUGAAG
2478





1740
GAUCAAGU U CAGAACAA
290
UUGUUCUG CUGAUGAG GCCGUUAGGC CGAA ACUUGAUC
2479





1741
AUCAAGUU C AGAACAAU
291
AUUGUUCU CUGAUGAG GCCGUUAGGC CGAA AACUUGAU
2480





1755
AAUGGCCU C AUUGAUGC
292
GCAUCAAU CUGAUGAG GCCGUUAGGC CGAA AGGCCAUU
2481





1758
GGCCUCAU U GAUGCUUU
293
AAAGCAUC CUGAUGAG GCCGUUAGGC CGAA AUGAGGCC
2482





1765
UUGAUGCU U UUGGGGCC
294
GGCCCCAA CUGAUGAG GCCGUUAGGC CGAA AGCAUCAA
2483





1766
UGAUGCUU U UGGGGCCC
295
GGGCCCCA CUGAUGAG GCCGUUAGGC CGAA AAGCAUCA
2484





1767
GAUGCUUU U GGGGCCCU
296
AGGGCCCC CUGAUGAG GCCGUUAGGC CGAA AAAGCAUC
2485





1776
GGGGCCCU U UCAUCAGG
297
CCUGAUGA CUGAUGAG GCCGUUAGGC CGAA AGGGCCCC
2486





1777
GGGCCCUU U CAUCAGGA
298
UCCUGAUG CUGAUGAG GCCGUUAGGC CGAA AAGGGCCC
2487





1778
GGCCCUUU C AUCAGGAA
299
UUCCUGAU CUGAUGAG GCCGUUAGGC CGAA AAAGGGCC
2488





1781
CCUUUCAU C AGGAAAUG
300
CAUUUCCU CUGAUGAG GCCGUUAGGC CGAA AUGAAAGG
2489





1797
GGAGCUGU C UCUCAGCG
301
CGCUGAGA CUGAUGAG GCCGUUAGGC CGAA ACAGCUCC
2490





1799
AGCUGUCU C UCAGCGCU
302
AGCGCUGA CUGAUGAG GCCGUUAGGC CGAA AGACAGCU
2491





1801
CUGUCUCU C AGCGCUCC
303
GGAGCGCU CUGAUGAG GCCGUUAGGC CGAA AGAGACAG
2492





1808
UCAGCGCU C CAUCCAGC
304
GCUGGAUG CUGAUGAG GCCGUUAGGC CGAA AGCGCUGA
2493





1812
CGCUCCAU C CAGCUUGA
305
UCAAGCUG CUGAUGAG GCCGUUAGGC CGAA AUGGAGCG
2494





1818
AUCCAGCU U GAGAGUAA
306
UUACUCUC CUGAUGAG GCCGUUAGGC CGAA AGCUGGAU
2495





1825
UUGAGAGU A AGGGAUUA
307
UAAUCCCU CUGAUGAG GCCGUUAGGC CGAA ACUCUCAA
2496





1832
UAAGGGAU U AACCCUCC
308
GGAGGGUU CUGAUGAG GCCGUUAGGC CGAA AUCCCUUA
2497





1833
AAGGGAUU A ACCCUCCA
309
UGGAGGGU CUGAUGAG GCCGUUAGGC CGAA AAUCCCUU
2498





1839
UUAACCCU C CAGAACAG
310
CUGUUCUG CUGAUGAG GCCGUUAGGC CGAA AGGGUUAA
2499





1872
ACAGUGAU C GUGGACAG
311
CUGUCCAC CUGAUGAG GCCGUUAGGC CGAA AUCACUGU
2500





1900
AGGACACU U UGUUUCUU
312
AAGAAACA CUGAUGAG GCCGUUAGGC CGAA AGUGUCCU
2501





1901
GGACACUU U GUUUCUUA
313
UAAGAAAC CUGAUGAG GCCGUUAGGC CGAA AACUGUCC
2502





1904
CACUUUGU U UCUUAUCA
314
UGAUAAGA CUGAUGAG GCCGUUAGGC CGAA ACAAAGUG
2503





1905
ACUUUGUU U CUUAUCAC
315
GUGAUAAG CUGAUGAG GCCGUUAGGC CGAA AACAAAGU
2504





1906
CUUUGUUU C UUAUCACC
316
GGUGAUAA CUGAUGAG GCCGUUAGGC CGAA AAACAAAG
2505





1908
UUGUUUCU U AUCACCUG
317
CAGGUGAU CUGAUGAG GCCGUUAGGC CGAA AGAAACAA
2506





1909
UGUUUCUU A UCACCUGG
318
CCAGGUGA CUGAUGAG GCCGUUAGGC CGAA AAGAAACA
2507





1911
UUUCUUAU C ACCUGGAC
319
GUCCAGGU CUGAUGAG GCCGUUAGGC CGAA AUAAGAAA
2508





1930
CGCAGCCU C CCCAAAUC
320
GAUUUGGG CUGAUGAG GCCGUUAGGC CGAA AGGCUGCG
2509





1938
CCCCAAAU C CUUCUCUG
321
CAGAGAAG CUGAUGAG GCCGUUAGGC CGAA AUUUGGGG
2510





1941
CAAAUCCU U CUCUGGGA
322
UCCCAGAG CUGAUGAG GCCGUUAGGC CGAA AGGAUUUG
2511





1942
AAAUCCUU C UCUGGGAU
323
AUCCCAGA CUGAUGAG GCCGUUAGGC CGAA AAGGAUUU
2512





1944
AUCCUUCU C UGGGAUCC
324
GGAUCCCA CUGAUGAG GCCGUUAGGC CGAA AGAAGGAU
2513





1951
UCUGGGAU C CCAGUGGA
325
UCCACUGG CUGAUGAG GCCGUUAGGC CGAA AUCCCAGA
2514





1976
AGGUGGCU U UGUAGUGG
326
CCACUACA CUGAUGAG GCCGUUAGGC CGAA AGCCACCU
2515





1977
GGUGGCUU U GUAGUGGA
327
UCCACUAC CUGAUGAG GCCGUUAGGC CGAA AAGCCACC
2516





1980
GGCUUUGU A GUGGACAA
328
UUGUCCAC CUGAUGAG GCCGUUAGGC CGAA ACAAAGCC
2517





2006
AAUGGCCU A CCUCCAAA
329
UUUGGAGG CUGAUGAG GCCGUUAGGC CGAA AGGCCAUU
2518





2010
GCCUACCU C CAAAUCCC
330
GGGAUUUG CUGAUGAG GCCGUUAGGC CGAA AGGUAGGC
2519





2016
CUCCAAAU C CCAGGCAU
331
AUGCCUGG CUGAUGAG GCCGUUAGGC CGAA AUUUGGAG
2520





2025
CCAGGCAU U GCUAAGGU
332
ACCUUAGC CUGAUGAG GCCGUUAGGC CGAA AUGCCUGG
2521





2029
GCAUUGCU A AGGUUGGC
333
GCCAACCU CUGAUGAG GCCGUUAGGC CGAA AGCAAUGC
2522





2034
GCUAAGGU U GGCACUUG
334
CAAGUGCC CUGAUGAG GCCGUUAGGC CGAA ACCUUAGC
2523





2041
UUGGCACU U GGAAAUAC
335
GUAUUUCC CUGAUGAG GCCGUUAGGC CGAA AGUGCCAA
2524





2048
UUGGAAAU A CAGUCUGC
336
GCAGACUG CUGAUGAG GCCGUUAGGC CGAA AUUUCCAA
2525





2053
AAUACAGU C UGCAAGCA
337
UGCUUGCA CUGAUGAG GCCGUUAGGC CGAA ACUGUAUU
2526





2066
AGCAAGCU C ACAAACCU
338
AGGUUUGU CUGAUGAG GCCGUUAGGC CGAA AGCUUGCU
2527





2075
ACAAACCU U GACCCUGA
339
UCAGGGUC CUGAUGAG GCCGUUAGGC CGAA AGGUUUGU
2528





2088
CUGACUGU C ACGUCCCG
340
CGGGACGU CUGAUGAG GCCGUUAGGC CGAA ACAGUCAG
2529





2093
UGUCACGU C CCGUGCGU
341
ACGCACGG CUGAUGAG GCCGUUAGGC CGAA ACGUGACA
2530





2102
CCGUGCGU C CAAUGCUA
342
UAGCAUUG CUGAUGAG GCCGUUAGGC CGAA ACGCACGG
2531





2110
CCAAUGCU A CCCUGCCU
343
AGGCAGGG CUGAUGAG GCCGUUAGGC CGAA AGCAUUGG
2532





2119
CCCUGCCU C CAAUUACA
344
UGUAAUUG CUGAUGAG GCCGUUAGGC CGAA AGGCAGGG
2533





2124
CCUCCAAU U ACAGUGAC
345
GUCACUGU CUGAUGAG GCCGUUAGGC CGAA AUUGGAGG
2534





2125
CUCCAAUU A CAGUGACU
346
AGUCACUG CUGAUGAG GCCGUUAGGC CGAA AAUUGGAG
2535





2134
CAGUGACU U CCAAAACG
347
CGUUUUGG CUGAUGAG GCCGUUAGGC CGAA AGUCACUG
2536





2135
AGUGACUU C CAAAACGA
348
UCGUUUUG CUGAUGAG GCCGUUAGGC CGAA AAGUCACU
2537





2162
CAGCAAAU U CCCCAGCC
349
GGCUGGGG CUGAUGAG GCCGUUAGGC CGAA AUUUGCUG
2538





2163
AGCAAAUU C CCCAGCCC
350
GGGCUGGG CUGAUGAG GCCGUUAGGC CGAA AAUUUGCU
2539





2173
CCAGCCCU C UGGUAGUU
351
AACUACCA CUGAUGAG GCCGUUAGGC CGAA AGGGCUGG
2540





2178
CCUCUGGU A GUUUAUGC
352
GCAUAAAC CUGAUGAG GCCGUUAGGC CGAA ACCAGAGG
2541





2181
CUGGUAGU U UAUGCAAA
353
UUUGCAUA CUGAUGAG GCCGUUAGGC CGAA ACUACCAG
2542





2182
UGGUAGUU U AUGCAAAU
354
AUUUGCAU CUGAUGAG GCCGUUAGGC CGAA AACUACCA
2543





2183
GGUAGUUU A UGCAAAUA
355
UAUUUGCA CUGAUGAG GCCGUUAGGC CGAA AAACUACC
2544





2191
AUGCAAAU A UUCGCCAA
356
UUGGCGAA CUGAUGAG GCCGUUAGGC CGAA AUUUGCAU
2545





2193
GCAAAUAU U CGCCAAGG
357
CCUUGGCG CUGAUGAG GCCGUUAGGC CGAA AUAUUUGC
2546





2194
CAAAUAUU C GCCAAGGA
358
UCCUUGGC CUGAUGAG GCCGUUAGGC CGAA AAUAUUUG
2547





2207
AGGAGCCU C CCCAAUUC
359
GAAUUGGG CUGAUGAG GCCGUUAGGC CGAA AGGCUCCU
2548





2214
UCCCCAAU U CUCAGGGC
360
GCCCUGAG CUGAUGAG GCCGUUAGGC CGAA AUUGGGGA
2549





2215
CCCCAAUU C UCAGGGCC
361
GGCCCUGA CUGAUGAG GCCGUUAGGC CGAA AAUUGGGG
2550





2217
CCAAUUCU C AGGGCCAG
362
CUGGCCCU CUGAUGAG GCCGUUAGGC CGAA AGAAUUGG
2551





2229
GCCAGUGU C ACAGCCCU
363
AGGGCUGU CUGAUGAG GCCGUUAGGC CGAA ACACUGGC
2552





2241
GCCCUGAU U GAAUCAGU
364
ACUGAUUC CUGAUGAG GCCGUUAGGC CGAA AUCAGGGC
2553





2246
GAUUGAAU C AGUGAAUG
365
CAUUCACU CUGAUGAG GCCGUUAGGC CGAA AUUCAAUC
2554





2265
AAAACAGU U ACCUUGGA
366
UCCAAGGU CUGAUGAG GCCGUUAGGC CGAA ACUGUUUU
2555





2266
AAACAGUU A CCUUGGAA
367
UUCCAAGG CUGAUGAG GCCGUUAGGC CGAA AACUGUUU
2556





2270
AGUUACCU U GGAACUAC
368
GUAGUUCC CUGAUGAG GCCGUUAGGC CGAA AGGUAACU
2557





2277
UUGGAACU A CUGGAUAZ
369
UUAUCCAG CUGAUGAG GCCGUUAGGC CGAA AGUUCCAA
2558





2284
UACUGGAU A AUGGAGCA
370
UGCUCCAU CUGAUGAG GCCGUUAGGC CGAA AUCCAGUA
2559





2305
CUGAUGCU A CUAAGGAU
371
AUCCUUAG CUGAUGAG GCCGUUAGGC CGAA AGCAUCAG
2560





2308
AUGCUACU A AGGAUGAC
372
GUCAUCCU CUGAUGAG GCCGUUAGGC CGAA AGUAGCAU
2561





2322
GACGGUGU C UACUCAAG
373
CUUGAGUA CUGAUGAG GCCGUUAGGC CGAA ACACCGUC
2562





2324
CGGUGUCU A CUCAAGGU
374
ACCUUGAG CUGAUGAG GCCGUUAGGC CGAA AGACACCG
2563





2327
UGUCUACU C AAGGUAUU
375
AAUACCUU CUGAUGAG GCCGUUAGGC CGAA AGUAGACA
2564





2333
CUCAAGGU A UUUCACAA
376
UUGUGAAA CUGAUGAG GCCGUUAGGC CGAA ACCUUGAG
2565





2335
CAAGGUAU U UCACAACU
377
AGUUGUGA CUGAUGAG GCCGUUAGGC CGAA AUACCUUG
2566





2336
AAGGUAUU U CACAACUU
378
AAGUUGUG CUGAUGAG GCCGUUAGGC CGAA AAUACCUU
2567





2337
AGGUAUUU C ACAACUUA
379
UAAGUUGU CUGAUGAG GCCGUUAGGC CGAA AAAUACCU
2568





2344
UCACAACU U AUGACACG
380
CGUGUCAU CUGAUGAG GCCGUUAGGC CGAA AGUUGUGA
2569





2345
CACAACUU A UGACACGA
381
UCGUGUCA CUGAUGAG GCCGUUAGGC CGAA AAGUUGUG
2570





2359
CGAAUGGU A GAUACAGU
382
ACUGUAUC CUGAUGAG GCCGUUAGGC CGAA ACCAUUCG
2571





2363
UGGUAGAU A CAGUGUAA
383
UUACACUG CUGAUGAG GCCGUUAGGC CGAA AUCUACCA
2572





2370
UACAGUGU A AAAGUGCG
384
CGCACUUU CUGAUGAG GCCGUUAGGC CGAA ACACUGUA
2573





2383
UGCGGGCU C UGGGAGGA
385
UCCUCCCA CUGAUGAG GCCGUUAGGC CGAA AGCCCGCA
2574





2394
GGAGGAGU U AACGCAGC
386
GCUGCGUU CUGAUGAG GCCGUUAGGC CGAA ACUCCUCC
2575





2395
GAGGAGUU A ACGCAGCC
387
GGCUGCGU CUGAUGAG GCCGUUAGGC CGAA AACUCCUC
2576





2418
AGAGUGAU A CCCCAGCA
388
UGCUGGGG CUGAUGAG GCCGUUAGGC CGAA AUCACUCU
2577





2441
AGCACUGU A CAUACCUG
389
CAGGUAUG CUGAUGAG GCCGUUAGGC CGAA ACAGUGCU
2578





2445
CUGUACAU A CCUGGCUG
390
CAGCCAGG CUGAUGAG GCCGUUAGGC CGAA AUGUACAG
2579





2457
GGCUGGAU U GAGAAUGA
391
UCAUUCUC CUGAUGAG GCCGUUAGGC CGAA AUCCAGCC
2580





2472
GAUGAAAU A CAAUGGAA
392
UUCCAUUG CUGAUGAG GCCGUUAGGC CGAA AUUUCAUC
2581





2482
AAUGGAAU C CACCAAGA
393
UCUUGGUG CUGAUGAG GCCGUUAGGC CGAA AUUCCAUU
2582





2499
CCUGAAAU U AAUAAGGA
394
UCCUUAUU CUGAUGAG GCCGUUAGGC CGAA AUUUCAGG
2583





2500
CUGAAAUU A AUAAGGAU
395
AUCCUUAU CUGAUGAG GCCGUUAGGC CGAA AAUUUCAG
2584





2503
AAAUUAAU A AGGAUGAU
396
AUCAUCCU CUGAUGAG GCCGUUAGGC CGAA AUUAAUUU
2585





2514
GAUGAUGU U CAACACAA
397
UUGUGUUG CUGAUGAG GCCGUUAGGC CGAA ACAUCAUC
2586





2515
AUGAUGUU C AACACAAG
398
CUUGUGUU CUGAUGAG GCCGUUAGGC CGAA AACAUCAU
2587





2533
AAGUGUGU U UCAGCAGA
399
UCUGCUGA CUGAUGAG GCCGUUAGGC CGAA ACACACUU
2588





2534
AGUGUGUU U CAGCAGAA
400
UUCUGCUG CUGAUGAG GCCGUUAGGC CGAA AACACACU
2589





2535
GUGUGUUU C AGCAGAAC
401
GUUCUGCU CUGAUGAG GCCGUUAGGC CGAA AAACACAC
2590





2546
CAGAACAU C CUCGGGAG
402
CUCCCGAG CUGAUGAG GCCGUUAGGC CGAA AUGUUCUG
2591





2549
AACAUCCU C GGGAGGCU
403
AGCCUCCC CUGAUGAG GCCGUUAGGC CGAA AGGAUGUU
2592





2558
GGGAGGCU C AUUUGUGG
404
CCACAAAU CUGAUGAG GCCGUUAGGC CGAA AGCCUCCC
2593





2561
AGGCUCAU U UGUGGCUU
405
AAGCCACA CUGAUGAG GCCGUUAGGC CGAA AUGAGCCU
2594





2562
GGCUCAUU U GUGGCUUC
406
GAAGCCAC CUGAUGAG GCCGUUAGGC CGAA AAUGAGCC
2595





2569
UUGUGGCU U CUGAUGUC
407
GACAUCAG CUGAUGAG GCCGUUAGGC CGAA AGCCACAA
2596





2570
UGUGGCUU C UGAUGUCC
408
GGACAUCA CUGAUGAG GCCGUUAGGC CGAA AAGCCACA
2597





2577
UCUGAUGU C CCAAAUGC
409
GCAUUUGG CUGAUGAG GCCGUUAGGC CGAA ACAUCAGA
2598





2587
CAAAUGCU C CCAUACCU
410
AGGUAUGG CUGAUGAG GCCGUUAGGC CGAA AGCAUUUG
2599





2592
GCUCCCAU A CCUGAUCU
411
AGAUCAGG CUGAUGAG GCCGUUAGGC CGAA AUGGGAGC
2600





2599
UACCUGAU C UCUUCCCA
412
UGGGAAGA CUGAUGAG GCCGUUAGGC CGAA AUCAGGUA
2601





2601
CCUGAUCU C UUCCCACC
413
GGUGGGAA CUGAUGAG GCCGUUAGGC CGAA AGAUCAGG
2602





2603
UGAUCUCU U CCCACCUG
414
CAGGUGGG CUGAUGAG GCCGUUAGGC CGAA AGAGAUCA
2603





2604
GAUCUCUU C CCACCUGG
415
CCAGGUGG CUGAUGAG GCCGUUAGGC CGAA AAGAGAUC
2604





2619
GGCCAAAU C ACCGACCU
416
AGGUCGGU CUGAUGAG GCCGUUAGGC CGAA AUUUGGCC
2605





2640
GCGGAAAU U CACGGGGG
417
CCCCCGUG CUGAUGAG GCCGUUAGGC CGAA AUUUCCGC
2606





2641
CGGAAAUU C ACGGGGGC
418
GCCCCCGU CUGAUGAG GCCGUUAGGC CGAA AAUUUCCG
2607





2653
GGGGCAGU C UCAUUAAU
419
AUUAAUGA CUGAUGAG GCCGUUAGGC CGAA ACUGCCCC
2608





2655
GGCAGUCU C AUUAAUCU
420
AGAUUAAU CUGAUGAG GCCGUUAGGC CGAA AGACUGCC
2609





2658
AGUCUCAU U AAUCUGAC
421
GUCAGAUU CUGAUGAG GCCGUUAGGC CGAA AUGAGACU
2610





2659
GUCUCAUU A AUCUGACU
422
AGUCAGAU CUGAUGAG GCCGUUAGGC CGAA AAUGAGAC
2611





2662
UCAUUAAU C UGACUUGG
423
CCAAGUCA CUGAUGAG GCCGUUAGGC CGAA AUUAAUGA
2612





2668
AUCUGACU U GGACAGCU
424
AGCUGUCC CUGAUGAG GCCGUUAGGC CGAA AGUCAGAU
2613





2677
GGACAGCU C CUGGGGAU
425
AUCCCCAG CUGAUGAG GCCGUUAGGC CGAA AGCUGUCC
2614





2689
GGGAUGAU U AUGACCAU
426
AUGGUCAU CUGAUGAG GCCGUUAGGC CGAA AUCAUCCC
2615





2690
GGAUGAUU A UGACCAUG
427
CAUGGUCA CUGAUGAG GCCGUUAGGC CGAA AAUCAUCC
2616





2707
GAACAGCU C ACAAGUAU
428
AUACUUGU CUGAUGAG GCCGUUAGGC CGAA AGCUGUUC
2617





2714
UCACAAGU A UAUCAUUC
429
GAAUGAUA CUGAUGAG GCCGUUAGGC CGAA ACUUGUGA
2618





2716
ACAAGUAU A UCAUUCGA
430
UCGAAUGA CUGAUGAG GCCGUUAGGC CGAA AUACUUGU
2619





2718
AAGUAUAU C AUUCGAAU
431
AUUCGAAU CUGAUGAG GCCGUUAGGC CGAA AUAUACUU
2620





2721
UAUAUCAU U CGAAUAAG
432
CUUAUUCG CUGAUGAG GCCGUUAGGC CGAA AUGAUAUA
2621





2722
AUAUCAUU C GAAUAAGU
433
ACUUAUUC CUGAUGAG GCCGUUAGGC CGAA AAUGAUAU
2622





2727
AUUCGAAU A AGUACAAG
434
CUUGUACU CUGAUGAG GCCGUUAGGC CGAA AUUCGAAU
2623





2731
GAAUAAGU A CAAGUAUU
435
AAUACUUG CUGAUGAG GCCGUUAGGC CGAA ACUUAUUC
2624





2737
GUACAAGU A UUCUUGAU
436
AUCAAGAA CUGAUGAG GCCGUUAGGC CGAA ACUUGUAC
2625





2739
ACAAGUAU U CUUGAUCU
437
AGAUCAAG CUGAUGAG GCCGUUAGGC CGAA AUACUUGU
2626





2740
CAAGUAUU C UUGAUCUC
438
GAGAUCAA CUGAUGAG GCCGUUAGGC CGAA AAUACUUG
2627





2742
AGUAUUCU U GAUCUCAG
439
CUGAGAUC CUGAUGAG GCCGUUAGGC CGAA AGAAUACU
2628





2746
UUCUUGAU C UCAGAGAC
440
GUCUCUGA CUGAUGAG GCCGUUAGGC CGAA AUCAAGAA
2629





2748
CUUGAUCU C AGAGACAA
441
UUGUCUCU CUGAUGAG GCCGUUAGGC CGAA AGAUCAAG
2630





2759
AGACAAGU U CAAUGAAU
442
AUUCAUUG CUGAUGAG GCCGUUAGGC CGAA ACUUGUCU
2631





2760
GACAAGUU C AAUGAAUC
443
GAUUCAUU CUGAUGAG GCCGUUAGGC CGAA AACUUGUC
2632





2768
CAAUGAAU C UCUUCAAG
444
CUUGAAGA CUGAUGAG GCCGUUAGGC CGAA AUUCAUUG
2633





2770
AUGAAUCU C UUCAAGUG
445
CACUUGAA CUGAUGAG GCCGUUAGGC CGAA AGAUUCAU
2634





2772
GAAUCUCU U CAAGUGAA
446
UUCACUUG CUGAUGAG GCCGUUAGGC CGAA AGAGAUUC
2635





2773
AAUCUCUU C AAGUGAAU
447
AUUCACUU CUGAUGAG GCCGUUAGGC CGAA AAGAGAUU
2636





2782
AAGUGAAU A CUACUGCU
448
AGCAGUAG CUGAUGAG GCCGUUAGGC CGAA AUUCACUU
2637





2785
UGAAUACU A CUGCUCUC
449
GAGAGCAG CUGAUGAG GCCGUUAGGC CGAA AGUAUUCA
2638





2791
CUACUGCU C UCAUCCCA
450
UGGGAUGA CUGAUGAG GCCGUUAGGC CGAA AGCAGUAG
2639





2793
ACUGCUCU C AUCCCAAA
451
UUUGGGAU CUGAUGAG GCCGUUAGGC CGAA AGAGCAGU
2640





2796
GCUCUCAU C CCAAAGGA
452
UCCUUUGG CUGAUGAG GCCGUUAGGC CGAA AUGAGAGC
2641





2813
AGCCAACU C UGAGGAAG
453
CUUCCUCA CUGAUGAG GCCGUUAGGC CGAA AGUUGGCU
2642





2823
GAGGAAGU C UUUUUGUU
454
AACAAAAA CUGAUGAG GCCGUUAGGC CGAA ACUUCCUC
2643





2825
GGAAGUCU U UUUGUUUA
455
UAAACAAA CUGAUGAG GCCGUUAGGC CGAA AGACUUCC
2644





2826
GAAGUCUU U UUGUUUAA
456
UUAAACAA CUGAUGAG GCCGUUAGGC CGAA AAGACUUC
2645





2827
AAGUCUUU U UGUUUAAA
457
UUUAAACA CUGAUGAG GCCGUUAGGC CGAA AAAGACUU
2646





2828
AGUCUUUU U GUUUAAAC
458
GUUUAAAC CUGAUGAG GCCGUUAGGC CGAA AAAAGACU
2647





2831
CUUUUUGU U UAAACCAG
459
CUGGUUUA CUGAUGAG GCCGUUAGGC CGAA ACAAAAAG
2648





2832
UUUUUGUU U AAACCAGA
460
UCUGGUUU CUGAUGAG GCCGUUAGGC CGAA AACAAAAA
2649





2833
UUUUGUUU A AACCAGAA
461
UUCUGGUU CUGAUGAG GCCGUUAGGC CGAA AAACAAAA
2650





2847
GAAAACAU U ACUUUUGA
462
UCAAAAGU CUGAUGAG GCCGUUAGGC CGAA AUGUUUUC
2651





2848
AAAACAUU A CUUUUGAA
463
UUCAAAAG CUGAUGAG GCCGUUAGGC CGAA AAUGUUUU
2652





2851
ACAUUACU U UUGAAAAU
464
AUUUUCAA CUGAUGAG GCCGUUAGGC CGAA AGUAAUGU
2653





2852
CAUUACUU U UGAAAAUG
465
CAUUUUCA CUGAUGAG GCCGUUAGGC CGAA AAGUAAUG
2654





2853
AUUACUUU U GAAAAUGG
466
CCAUUUUC CUGAUGAG GCCGUUAGGC CGAA AAAGUAAU
2655





2869
GCACAGAU C UUUUCAUU
467
AAUGAAAA CUGAUGAG GCCGUUAGGC CGAA AUCUGUGC
2656





2871
ACAGAUCU U UUCAUUGC
468
GCAAUGAA CUGAUGAG GCCGUUAGGC CGAA AGAUCUGU
2657





2872
CAGAUCUU U UCAUUGCU
469
AGCAAUGA CUGAUGAG GCCGUUAGGC CGAA AAGAUCUG
2658





2873
AGAUCUUU U CAUUGCUA
470
UAGCAAUG CUGAUGAG GCCGUUAGGC CGAA AAAGAUCU
2659





2874
GAUCUUUU C AUUGCUAU
471
AUAGCAAU CUGAUGAG GCCGUUAGGC CGAA AAAAGAUC
2660





2877
CUUUUCAU U GCUAUUCA
472
UGAAUAGC CUGAUGAG GCCGUUAGGC CGAA AUGAAAAG
2661





2881
UCAUUGCU A UUCAGGCU
473
AGCCUGAA CUGAUGAG GCCGUUAGGC CGAA AGCAAUGA
2662





2883
AUUGCUAU U CAGGCUGU
474
ACAGCCUG CUGAUGAG GCCGUUAGGC CGAA AUAGCAAU
2663





2884
UUGCUAUU C AGGCUGUU
475
AACAGCCU CUGAUGAG GCCGUUAGGC CGAA AAUAGCAA
2664





2892
CAGGCUGU U GAUAAGGU
476
ACCUUAUC CUGAUGAG GCCGUUAGGC CGAA ACAGCCUG
2665





2896
CUGUUGAU A AGGUCGAU
477
AUCGACCU CUGAUGAG GCCGUUAGGC CGAA AUCAACAG
2666





2901
GAUAAGGU C GAUCUGAA
478
UUCAGAUC CUGAUGAG GCCGUUAGGC CGAA ACCUUAUC
2667





2905
AGGUCGAU C UGAAAUCA
479
UGAUUUCA CUGAUGAG GCCGUUAGGC CGAA AUCGACCU
2668





2912
UCUGAAAU C AGAAAUAU
480
AUAUUUCU CUGAUGAG GCCGUUAGGC CGAA AUUUCAGA
2669





2919
UCAGAAAU A UCCAACAU
481
AUGUUGGA CUGAUGAG GCCGUUAGGC CGAA AUUUCUGA
2670





2921
AGAAAUAU C CAACAUUG
482
CAAUGUUG CUGAUGAG GCCGUUAGGC CGAA AUAUUUCU
2671





2928
UCCAACAU U GCACGAGU
483
ACUCGUGC CUGAUGAG GCCGUUAGGC CGAA AUGUUGGA
2672





2937
GCACGAGU A UCUUUGUU
484
AACAAAGA CUGAUGAG GCCGUUAGGC CGAA ACUCGUGC
2673





2939
ACGAGUAU C UUUGUUUA
485
UAAACAAA CUGAUGAG GCCGUUAGGC CGAA AUACUCGU
2674





2941
GAGUAUCU U UGUUUAUU
486
AAUAAACA CUGAUGAG GCCGUUAGGC CGAA AGAUACUC
2675





2942
AGUAUCUU U GUUUAUUC
487
GAAUAAAC CUGAUGAG GCCGUUAGGC CGAA AAGAUACU
2676





2945
AUCUUUGU U UAUUCCUC
488
GAGGAAUA CUGAUGAG GCCGUUAGGC CGAA ACAAAGAU
2677





2946
UCUUUGUU U AUUCCUCC
489
GGAGGAAU CUGAUGAG GCCGUUAGGC CGAA AACAAAGA
2678





2947
CUUUGUUU A UUCCUCCA
490
UGGAGGAA CUGAUGAG GCCGUUAGGC CGAA AAACAAAG
2679





2949
UUGUUUAU U CCUCCACA
491
UGUGGAGG CUGAUGAG GCCGUUAGGC CGAA AUAAACAA
2680





2950
UGUUUAUU C CUCCACAG
492
CUGUGGAG CUGAUGAG GCCGUUAGGC CGAA AAUAAACA
2681





2953
UUAUUCCU C CACAGACU
493
AGUCUGUG CUGAUGAG GCCGUUAGGC CGAA AGGAAUAA
2682





2962
CACAGACU C CGCCAGAG
494
CUCUGGCG CUGAUGAG GCCGUUAGGC CGAA AGUCUGUG
2683





2977
AGACACCU A GUCCUGAU
495
AUCAGGAC CUGAUGAG GCCGUUAGGC CGAA AGGUGUCU
2684





2980
CACCUAGU C CUGAUGAA
496
UUCAUCAG CUGAUGAG GCCGUUAGGC CGAA ACUAGGUG
2685





2993
UGAAACGU C UGCUCCUU
497
AAGGAGCA CUGAUGAG GCCGUUAGGC CGAA ACGUUUCA
2686





2998
CGUCUGCU C CUUGUCCU
498
AGGACAAG CUGAUGAG GCCGUUAGGC CGAA AGCAGACG
2687





3001
CUGCUCCU U GUCCUAAU
499
AUUAGGAC CUGAUGAG GCCGUUAGGC CGAA ACAAGGAG
2688





3004
CUCCUUGU C CUAAUAUU
500
AAUAUUAG CUGAUGAG GCCGUUAGGC CGAA ACAAGGAG
2689
2689





3007
CUUGUCCU A AUAUUCAU
501
AUGAAUAU CUGAUGAG GCCGUUAGGC CGAA AGGACAAG
2690





3010
GUCCUAAU A UUCAUAUC
502
GAUAUGAA CUGAUGAG GCCGUUAGGC CGAA AUUAGGAC
2691





3012
CCUAAUAU U CAUAUCAA
503
UUGAUAUG CUGAUGAG GCCGUUAGGC CGAA AUAUUAGG
2692





3013
CUAAUAUU C AUAUCAAC
504
GUUGAUAU CUGAUGAG GCCGUUAGGC CGAA AZUAUUAG
2693





3016
AUAUUCAU A UCAACAGC
505
GCUGUUGA CUGAUGAG GCCGUUAGGC CGAA AUGAAUAU
2694





3018
AUUCAUAU C AACAGCAC
506
GUGCUGUU CUGAUGAG GCCGUUAGGC CGAA AUAUGAAU
2695





3030
AGCACCAU U CCUGGCAU
507
AUGCCAGG CUGAUGAG GCCGUUAGGC CGAA AUGGUGCU
2696





3031
GCACCAUU C CUGGCAUU
508
AAUGCCAG CUGAUGAG GCCGUUAGGC CGAA AAUGGUGC
2697





3039
CCUGGCAU U CACAUUUU
509
AAAAUGUG CUGAUGAG GCCGUUAGGC CGAA AUGCCAGG
2698





3040
CUGGCAUU C ACAUUUUA
510
UAAAAUGU CUGAUGAG GCCGUUAGGC CGAA AAUGCCAG
2699





3045
AUUCACAU U UUAAAAAU
511
AUUUUUAA CUGAUGAG GCCGUUAGGC CGAA AUGUGAAU
2700





3046
UUCACAUU U UAAAAAUU
512
AAUUUUUA CUGAUGAG GCCGUUAGGC CGAA AAUGUGAA
2701





3047
UCACAUUU U AAAAAUUA
513
UAAUUUUU CUGAUGAG GCCGUUAGGC CGAA AAAUGUGA
2702





3048
CACAUUUU A AAAAUUAU
514
AUAAUUUU CUGAUGAG GCCGUUAGGC CGAA AAAAUGUG
2703





3054
UUAAAAAU U AUGUGGAA
515
UUCCACAU CUGAUGAG GCCGUUAGGC CGAA AUUUUUAA
2704





3055
UAAAAAUU A UGUGGAAG
516
CUUCCACA CUGAUGAG GCCGUUAGGC CGAA AAUUUUUA
2705





3069
AAGUGGAU A GGAGAACU
517
AGUUCUCC CUGAUGAG GCCGUUAGGC CGAA AUCCACUU
2706





3086
GCAGCUGU C AAUAGCCU
518
AGGCUAUU CUGAUGAG GCCGUUAGGC CGAA ACAGCUGC
2707





3090
CUGUCAAU A GCCUAGGG
519
CCCUAGGC CUGAUGAG GCCGUUAGGC CGAA AUUGACAG
2708





3095
AAUAGCCU A CGGCUGAA
520
UUCAGCCC CUGAUCAG GCCGUUAGGC CGAA AGGCUAUU
2709





3105
GGCUGAAU U UUUGUCAG
521
CUGACAAA CUGAUGAG GCCGUUAGGC CGAA AUUCAGCC
2710





3106
GCUGAAUU U UUGUCAGA
522
UCUGACAA CUGAUGAG GCCGUUAGGC CGAA AAUUCAGC
2711





3107
CUGAAUUU U UGUCAGAU
523
AUCUGACA CUGAUGAG GCCGUUAGGC CGAA AAAUUCAG
2712





3108
UGAAUUUU U GUCAGAUA
524
UAUCUGAC CUGAUGAG GCCGUUAGGC CGAA AAAAUUCA
2713





3111
AUUUUUGU C AGAUAAAU
525
AUUUAUCU CUGAUGAG GCCGUUAGGC CGAA ACAAAAAU
2714





3116
UGUCAGAU A AAUAAAAU
526
AUUUUAUU CUGAUGAG GCCGUUAGGC CGAA AUCUGACA
2715





3120
AGAUAAAU A AAAUAAAU
527
AUUUAUUU CUGAUGAG GCCGUUAGGC CGAA AUUUAUCU
2716





3125
AAUAAAAU A AAUCAUUC
528
GAAUGAUU CUGAUGAG GCCGUUAGGC CGAA AUUUUAUU
2717





3129
AAAUAAAU C AUUCAUCC
529
GGAUGAAU CUGAUGAG GCCGUUAGGC CGAA AUUUAUUU
2718





3132
UAAAUCAU U CAUCCUUU
530
AAAGGAUG CUGAUGAG GCCGUUAGGC CGAA AUGAUUUA
2719





3133
AAAUCAUU C AUCCUUUU
531
AAAAGGAU CUGAUGAG GCCGUUAGGC CGAA AAUGAUUU
2720





3136
UCAUUCAU C CUUUUUUU
532
AAAAAAAG CUGAUGAG GCCGUUAGGC CGAA AUGAAUGA
2721





3139
UUCAUCCU U UUUUUGAU
533
AUCAAAAA CUGAUGAG GCCGUUAGGC CGAA AGGAUGAA
2722





3140
UCAUCCUU U UUUUGAUU
534
AAUCAAAA CUGAUGAG GCCGUUAGGC CGAA AAGGAUGA
2723





3141
CAUCCUUU U UUUGAUUA
535
UAAUCAAA CUGAUGAG GCCGUUAGGC CGAA AAAGGAUG
2724





3142
AUCCUUUU U UUGAUUAU
536
AUAAUCAA CUGAUGAG GCCGUUAGGC CGAA AAAAGGAU
2725





3143
UCCUUUUU U UGAUUAUA
537
UAUAAUCA CUGAUGAG GCCGUUAGGC CGAA AAAAAGGA
2726





3144
CCUUUUUU U GAUUAUAA
538
UUAUAAUC CUGAUGAG GCCGUUAGGC CGAA AAAAAAGG
2727





3148
UUUUUGAU U AUAAAAUU
539
AAUUUUAU CUGAUGAG GCCGUUAGGC CGAA AUCAAAAA
2728





3149
UUUUGAUU A UAAAAUUU
540
AAAUUUUA CUGAUGAG GCCGUUAGGC CGAA AAUCAAAA
2729





3151
UUGAUUAU A AAAUUUUC
541
GAAAAUUU CUGAUGAG GCCGUUAGGC CGAA AUAAUCAA
2730





3156
UAUAAAAU U UUCUAAAA
542
UUUUAGAA CUGAUGAG GCCGUUAGGC CGAA AUUUUAUA
2731





3157
AUAAAAUU U UCUAAAAU
543
AUUUUAGA CUGAUGAG GCCGUUAGGC CGAA AAUUUUAU
2732





3158
UAAAAUUU U CUAAAAUG
544
CAUUUUAG CUGAUGAG GCCGUUAGGC CGAA AAAUUUUA
2733





3159
AAAAUUUU C UAAAAUGU
545
ACAUUUUA CUGAUGAG GCCGUUAGGC CGAA AAAAUUUU
2734





3161
AAUUUUCU A AAAUGUAU
546
AUACAUUU CUGAUGAG GCCGUUAGGC CGAA AGAAAAUU
2735





3168
UAAAAUGU A UUUUAGAC
547
GUCUAAAA CUGAUGAG GCCGUUAGGC CGAA ACAUUUUA
2736





3170
AAAUGUAU U UUAGACUU
548
AAGUCUAA CUGAUGAG GCCGUUAGGC CGAA AUACAUUU
2737





3260
AAAUGUAU U UUAGACUU
548
AAGUCUAA CUGAUGAG GCCGUUAGGC CGAA AUACAUUU
2737





3171
AAUGUAUU U UAGACUUC
549
GAAGUCUA CUGAUGAG GCCGUUAGGC CGAA AAUACAUU
2738





3261
AAUGUAUU U UAGACUUC
549
GAAGUCUA CUGAUGAG GCCGUUAGGC CGAA AAUACAUU
2738





3172
AUGUAUUU U AGACUUCC
550
GGAAGUCU CUGAUGAG GCCGUUAGGC CGAA AAAUACAU
2739





3262
AUGUAUUU U AGACUUCC
550
GGAAGUCU CUGAUGAG GCCGUUAGGC CGAA AAAUACAU
2739





3173
UGUAUUUU A GACUUCCU
551
AGGAAGUC CUGAUGAG GCCGUUAGGC CGAA AAAAUACA
2740





3263
UGUAUUUU A GACUUCCU
551
AGGAAGUC CUGAUGAG GCCGUUAGGC CGAA AAAAUACA
2740





3178
UUUAGACU U CCUGUAGG
552
CCUACAGG CUGAUGAG GCCGUUAGGC CGAA AGUCUAAA
2741





3268
UUUAGACU U CCUGUAGG
552
CCUACAGG CUGAUGAG GCCGUUAGGC CGAA AGUCUAAA
2741





3179
UUAGACUU C CUGUAGGG
553
CCCUACAG CUGAUGAG GCCGUUAGGC CGAA AAGUCUAA
2742





3269
UUAGACUU C CUGUAGGG
553
CCCUACAG CUGAUGAG GCCGUUAGGC CGAA AAGUCUAA
2742





3184
CUUCCUGU A GGGGGCGA
554
UCGCCCCC CUGAUGAG GCCGUUAGGC CGAA ACAGGAAG
2743





3274
CUUCCUGU A GGGGGCGA
554
UCGCCCCC CUGAUGAG GCCGUUAGGC CGAA ACAGGAAG
2743





3194
GGGGCGAU A UACUAAAU
555
AUUUAGUA CUGAUGAG GCCGUUAGGC CGAA AUCGCCCC
2744





3247
GGGGCGAU A UACUAAAU
555
AUUUAGUA CUGAUGAG GCCGUUAGGC CGAA AUCGCCCC
2744





3196
GGCGAUAU A CUAAAUGU
556
ACAUUUAG CUGAUGAG GCCGUUAGGC CGAA AUAUCGCC
2745





3249
GGCGAUAU A CUAAAUGU
556
ACAUUUAG CUGAUGAG GCCGUUAGGC CGAA AUAUCGCC
2745





3199
GAUAUACU A AAUGUAUA
557
UAUACAUU CUGAUGAG GCCGUUAGGC CGAA AGUAUAUC
2746





3205
CUAAAUGU A UAUAGUAC
558
GUACUAUA CUGAUGAG GCCGUUAGGC CGAA ACAUUUAG
2747





3207
AAAUGUAU A UAGUACAU
559
AUGUACUA CUGAUGAG GCCGUUAGGC CGAA AUACAUUU
2748





3209
AUGUAUAU A GUACAUUU
560
AAAUGUAC CUGAUGAG GCCGUUAGGC CGAA AUAUACAU
2749





3212
UAUAUAGU A CAUUUAUA
561
UAUAAAUG CUGAUGAG GCCGUUAGGC CGAA ACUAUAUA
2750





3216
UAGUACAU U UAUACUAA
562
UUAGUAUA CUGAUGAG GCCGUUAGGC CGAA AUGUACUA
2751





3217
AGUACAUU U AUACUAAA
563
UUUAGUAU CUGAUGAG GCCGUUAGGC CGAA AAUGUACU
2752





3218
GUACAUUU A UACUAAAU
564
AUUUAGUA CUGAUGAG GCCGUUAGGC CGAA AAAUGUAC
2753





3220
ACAUUUAU A CUAAAUGU
565
ACAUUUAG CUGAUGAG GCCGUUAGGC CGAA AUAAAUGU
2754





3223
UUUAUACU A AAUGUAUU
566
AAUACAUU CUGAUGAG GCCGUUAGGC CGAA AGUAUAAA
2755





3229
CUAAAUGU A UUCCUGUA
567
UACAGGAA CUGAUGAG GCCGUUAGGC CGAA ACAUUUAG
2756





3231
AAAUGUAU U CCUGUAGG
568
CCUACAGG CUGAUGAG GCCGUUAGGC CGAA AUACAUUU
2757





3232
AAUGUAUU C CUGUAGGG
569
CCCUACAG CUGAUGAG GCCGUUAGGC CGAA AAUACAUU
2758





3237
AUUCCUGU A GGGGGCGA
570
UCGCCCCC CUGAUGAG GCCGUUAGGC CGAA ACAGGAAU
2759





3252
GAUAUACU A AAUGUAUU
571
AAUACAUU CUGAUGAG GCCGUUAGGC CGAA AGUAUAUC
2760





3258
CUAAAUGU A UUUUAGAC
572
GUCUAAAA CUGAUGAG GCCGUUAGGC CGAA ACAUUUAG
2761





3284
GGGGCGAU A AAAUAAAA
573
UUUUAUUU CUGAUGAG GCCGUUAGGC CGAA AUCGCCCC
2762





3289
GAUAAAAU A AAAUGCUA
574
UAGCAUUU CUGAUGAG GCCGUUAGGC CGAA AUUUUAUC
2763





3297
AAAAUGCU A AACAACUG
575
CAGUUGUU CUGAUGAG GCCGUUAGGC CGAA AGCAUUUU
2764






Input Sequence = NM_001285. Cut Site = UH/.




Arm Length = 8. Core Sequence = CUGAUGAG GCCGUUAGGC CGAA




Underlined region can be any X sequence or linker, as described herein.




NM_001285 (Homo sapiens chloride channel, calcium activated, 1 (CLCA1) mRNA, 3311 bp)








[0191]

4





TABLE IV










Human CLCA1 Inozyme and Target Sequence 249.021















Rz




Seq ID

Seq ID


Pos
Substrate
No.
Inozyme
No.














10
GCUAAUGC U UUUGGUAC
576
GUACCAAA CUGAUGAG GCCGUUAGGC CGAA ICAUUAGC
2765





19
UUUGGUAC A AAUGGAUG
577
CAUCCAUU CUGAUGAG GCCGUUAGGC CGAA IUACCAAA
2766





50
AUAUUUUC U UGUUUAAG
578
CUUAAACA CUGAUGAG GCCGUUAGGC CGAA IAAAAUAU
2767





65
AGGGGAGC A UGAAGAGG
579
CCUCUUCA CUGAUGAG GCCGUUAGGC CGAA ICUCCCCU
2768





89
GUUAUGUC A AGCAUCUG
580
CAGAUGCU CUGAUGAG GCCGUUAGGC CGAA IACAUAAC
2769





93
UGUCAAGC A UCUGGCAC
581
GUGCCAGA CUGAUGAG GCCGUUAGGC CGAA ICUUGACA
2770





96
CAAGCAUC U GGCACAGC
582
GCUGUGCC CUGAUGAG GCCGUUAGGC CGAA IAUGCUUG
2771





100
CAUCUGGC A CAGCUGAA
583
UUCAGCUG CUGAUGAG GCCGUUAGGC CGAA ICCAGAUG
2772





102
UCUGGCAC A GCUGAAGG
584
CCUUCAGC CUGAUGAG GCCGUUAGGC CGAA IUGCCAGA
2773





105
GGCACAGC U GAAGGCAG
585
CUGCCUUC CUGAUGAG GCCGUUAGGC CGAA ICUGUGCC
2774





112
CUGAAGGC A GAUGGAAA
586
UUUCCAUC CUGAUGAG GCCGUUAGGC CGAA ICCUUCAG
2775





128
AUAUUUAC A AGUACGCA
587
UGCGUACU CUGAUGAG GCCGUUAGGC CGAA IUAAAUAU
2776





136
AAGUACGC A AUUUGAGA
588
UCUCAAAU CUGAUGAG GCCGUUAGGC CGAA ICGUACUU
2777





146
UUUGAGAC U AAGAUAUU
589
AAUAUCUU CUGAUGAG GCCGUUAGGC CGAA IUCUCAAA
2778





161
UUGUUAUC A UUCUCCUA
590
UAGGAGAA CUGAUGAG GCCGUUAGGC CGAA IAUAACAA
2779





165
UAUCAUUC U CCUAUUGA
591
UCAAUAGG CUGAUGAG GCCGUUAGGC CGAA IAAUGAUA
2780





167
UCAUUCUC C UAUUGAAG
592
CUUCAAUA CUGAUGAG GCCGUUAGGC CGAA IAGAAUGA
2781





168
CAUUCUCC U AUUGAAGA
593
UCUUCAAU CUGAUGAG GCCGUUAGGC CGAA IGAGAAUG
2782





178
UUGAAGAC A AGAGCAAU
594
AUUGCUCU CUGAUGAG GCCGUUAGGC CGAA IUCUUCAA
2783





184
ACAAGAGC A AUAGUAAA
595
UUUACUAU CUGAUGAG GCCGUUAGGC CGAA ICUCUUGU
2784





195
AGUAAAAC A CAUCAGGU
596
ACCUGAUG CUGAUGAG GCCGUUAGGC CGAA IUUUUACU
2785





197
UAAAACAC A UCAGGUCA
597
UGACCUGA CUGAUGAG GCCGUUAGGC CGAA IUGUUUUA
2786





200
AACACAUC A GGUCAGGG
598
CCCUGACC CUGAUGAG GCCGUUAGGC CGAA IAUGUGUU
2787





205
AUCAGGUC A GGGGGUUA
599
UAACCCCC CUGAUGAG GCCGUUAGGC CGAA IACCUGAU
2788





219
UUAAAGAC C UGUGAUAA
600
UUAUCACA CUGAUGAG GCCGUUAGGC CGAA IUCUUUAA
2789





220
UAAAGACC U GUGAUAAA
601
UUUAUCAC CUGAUGAG GCCGUUAGGC CGAA IGUCUUUA
2790





230
UGAUAAAC C ACUUCCGA
602
UCGGAAGU CUGAUGAG GCCGUUAGGC CGAA IUUUAUCA
2791





231
GAUAAACC A CUUCCGAU
603
AUCGGAAG CUGAUGAG GCCGUUAGGC CGAA IGUUUAUC
2792





233
UAAACCAC U UCCGAUAA
604
UUAUCGGA CUGAUGAG GCCGUUAGGC CGAA IUGGUUUA
2793





236
ACCACUUC C GAUAAGUU
605
AACUUAUC CUGAUGAG GCCGUUAGGC CGAA IAAGUGGU
2794





258
CGUGUGUC U AUAUUUUC
606
GAAAAUAU CUGAUGAG GCCGUUAGGC CGAA IACACACG
2795





267
AUAUUUUC A UAUCUGUA
607
UACAGAUA CUGAUGAG GCCGUUAGGC CGAA IAAAAUAU
2796





272
UUCAUAUC U GUAUAUAU
608
AUAUAUAC CUGAUGAG GCCGUUAGGC CGAA IAUAUGAA
2797





299
AGAAAGAC A CCUUCGUA
609
UACGAAGG CUGAUGAG GCCGUUAGGC CGAA IUCUUUCU
2798





301
AAAGACAC C UUCGUAAC
610
GUUACGAA CUGAUGAG GCCGUUAGGC CGAA IUGUCUUU
2799





302
AAGACACC U UCGUAACC
611
GGUUACGA CUGAUGAG GCCGUUAGGC CGAA IGUGUCUU
2800





310
UUCGUAAC C CGCAUUUU
612
AAAAUGCG CUGAUGAG GCCGUUAGGC CGAA IUUACGAA
2801





311
UCGUAACC C GCAUUUUC
613
GAAAAUGC CUGAUGAG GCCGUUAGGC CGAA IGUUACGA
2802





314
UAACCCGC A UUUUCCAA
614
UUGGAAAA CUGAUGAG GCCGUUAGGC CGAA ICGGGUUA
2803





320
GCAUUUUC C AAAGAGAG
615
CUCUCUUU CUGAUGAG GCCGUUAGGC CGAA IAAAAUGC
2804





321
CAUUUUCC A AAGAGAGG
616
CCUCUCUU CUGAUGAG GCCGUUAGGC CGAA IGAAAAUG
2805





334
GAGGAAUC A CAGGGAGA
617
UCUCCCUG CUGAUGAG GCCGUUAGGC CGAA IAUUCCUC
2806





336
GGAAUCAC A GGGAGAUG
618
CAUCUCCC CUGAUGAG GCCGUUAGGC CGAA IUGAUUCC
2807





348
AGAUGUAC A GCAAUGGG
619
CCCAUUGC CUGAUGAG GCCGUUAGGC CGAA IUACAUCU
2808





351
UGUACAGC A AUGGGGCC
620
GGCCCCAU CUGAUGAG GCCGUUAGGC CGAA ICUGUACA
2809





359
AAUGGGGC C AUUUAAGA
621
UCUUAAAU CUGAUGAG GCCGUUAGGC CGAA ICCCCAUU
2810





360
AUGGGGCC A UUUAAGAG
622
CUCUUAAA CUGAUGAG GCCGUUAGGC CGAA IGCCCCAU
2811





372
AAGAGUUC U GUGUUCAU
623
AUGAACAC CUGAUGAG GCCGUUAGGC CGAA IAACUCUU
2812





379
CUGUGUUC A UCUUGAUU
624
AAUCAAGA CUGAUGAG GCCGUUAGGC CGAA IAACACAG
2813





382
UGUUCAUC U UGAUUCUU
625
AAGAAUCA CUGAUGAG GCCGUUAGGC CGAA IAUGAACA
2814





389
CUUGAUUC U UCACCUUC
626
GAAGGUGA CUGAUGAG GCCGUUAGGC CGAA IAAUCAAG
2815





392
GAUUCUUC A CCUUCUAG
627
CUAGAAGG CUGAUGAG GCCGUUAGGC CGAA IAAGAAUC
2816





394
UUCUUCAC C UUCUAGAA
628
UUCUAGAA CUGAUGAG GCCGUUAGGC CGAA IUGAAGAA
2817





395
UCUUCACC U UCUAGAAG
629
CUUCUAGA CUGAUGAG GCCGUUAGGC CGAA IGUGAAGA
2818





398
UCACCUUC U AGAAGGGG
630
CCCCUUCU CUGAUGAG GCCGUUAGGC CGAA IAAGGUGA
2819





408
GAAGGGGC C CUGAGUAA
631
UUACUCAG CUGAUGAG GCCGUUAGGC CGAA ICCCCUUC
2820





409
AAGGGGCC C UGAGUAAU
632
AUUACUCA CUGAUGAG GCCGUUAGGC CGAA IGCCCCUU
2821





410
AGGGGCCC U GAGUAAUU
633
AAUUACUC CUGAUGAG GCCGUUAGGC CGAA IGGCCCCU
2822





420
AGUAAUUC A CUCAUUCA
634
UGAAUGAG CUGAUGAG GCCGUUAGGC CGAA IAAUUACU
2823





422
UAAUUCAC U CAUUCAGC
635
GCUGAAUG CUGAUGAG GCCGUUAGGC CGAA IUGAAUUA
2824





424
AUUCACUC A UUCAGCUG
636
CAGCUGAA CUGAUGAG GCCGUUAGGC CGAA IAGUGAAU
2825





428
ACUCAUUC A GCUGAACA
637
UGUUCAGC CUGAUGAG GCCGUUAGGC CGAA IAAUGAGU
2826





431
CAUUCAGC U GAACAACA
638
UGUUGUUC CUGAUGAG GCCGUUAGGC CGAA ICUGAAUG
2827





436
AGCUGAAC A ACAAUGGC
639
GCCAUUGU CUGAUGAG GCCGUUAGGC CGAA IUUCAGCU
2828





439
UGAACAAC A AUGGCUAU
640
AUAGCCAU CUGAUGAG GCCGUUAGGC CGAA IUUGUUCA
2829





445
ACAAUGGC U AUGAAGGC
641
GCCUUCAU CUGAUGAG GCCGUUAGGC CGAA ICCAUUGU
2830





454
AUGAAGGC A UUGUCGUU
642
AACGACAA CUGAUGAG GCCGUUAGGC CGAA ICCUUCAU
2831





465
GUCGUUGC A AUCGACCC
643
GGGUCGAU CUGAUGAG GCCGUUAGGC CGAA ICAACGAC
2832





472
CAAUCGAC C CCAAUGUG
644
CACAUUGG CUGAUGAG GCCGUUAGGC CGAA IUCGAUUG
2833





473
AAUCGACC C CAAUGUGC
645
GCACAUUG CUGAUGAG GCCGUUAGGC CGAA IGUCGAUU
2834





474
AUCGACCC C AAUGUGCC
646
GGCACAUU CUGAUGAG GCCGUUAGGC CGAA IGGUCGAU
2835





475
UCGACCCC A AUGUGCCA
647
UGGCACAU CUGAUGAG GCCGUUAGGC CGAA IGGGUCGA
2836





482
CAAUGUGC C AGAAGAUG
648
CAUCUUCU CUGAUGAG GCCGUUAGGC CGAA ICACAUUG
2837





483
AAUGUGCC A GAAGAUGA
649
UCAUCUUC CUGAUGAG GCCGUUAGGC CGAA IGCACAUU
2838





495
GAUGAAAC A CUCAUUCA
650
UGAAUGAG CUGAUGAG GCCGUUAGGC CGAA IUUUCAUC
2839





497
UGAAACAC U CAUUCAAC
651
GUUGAAUG CUGAUGAG GCCGUUAGGC CGAA IUGUUUCA
2840





499
AAACACUC A UUCAACAA
652
UUGUUGAA CUGAUGAG GCCGUUAGGC CGAA IAGUGUUU
2841





503
ACUCAUUC A ACAAAUAA
653
UUAUUUGU CUGAUGAG GCCGUUAGGC CGAA IAAUGAGU
2842





506
CAUUCAAC A AAUAAAGG
654
CCUUUAUU CUGAUGAG GCCGUUAGGC CGAA IUUGAAUG
2843





517
UAAAGGAC A UGGUGACC
655
GGUCACCA CUGAUGAG GCCGUUAGGC CGAA IUCCUUUA
2844





525
AUGGUGAC C CAGGCAUC
656
GAUGCCUG CUGAUGAG GCCGUUAGGC CGAA IUCACCAU
2845





526
UGGUGACC C AGGCAUCU
657
AGAUGCCU CUGAUGAG GCCGUUAGGC CGAA IGUCACCA
2846





527
GGUGACCC A GGCAUCUC
658
GAGAUGCC CUGAUGAG GCCGUUAGGC CGAA IGGUCACC
2847





531
ACCCAGGC A UCUCUGUA
659
UACAGAGA CUGAUGAG GCCGUUAGGC CGAA ICCUGGGU
2848





534
CAGGCAUC U CUGUAUCU
660
AGAUACAG CUGAUGAG GCCGUUAGGC CGAA IAUGCCUG
2849





536
GGCAUCUC U GUAUCUGU
661
ACAGAUAC CUGAUGAG GCCGUUAGGC CGAA IAGAUGCC
2850





542
UCUGUAUC U GUUUGAAG
662
CUUCAAAC CUGAUGAG GCCGUUAGGC CGAA IAUACAGA
2851





552
UUUGAAGC U ACAGGAAA
663
UUUCCUGU CUGAUGAG GCCGUUAGGC CGAA ICUUCAAA
2852





555
GAAGCUAC A GGAAAGCG
664
CGCUUUCC CUGAUGAG GCCGUUAGGC CGAA IUAGCUUC
2853





574
UUUAUUUC A AAAAUGUU
665
AACAUUUU CUGAUGAG GCCGUUAGGC CGAA IAAAUAAA
2854





585
AAUGUUGC C AUUUUGAU
666
AUCAAAAU CUGAUGAG GCCGUUAGGC CGAA ICAACAUU
2855





586
AUGUUGCC A UUUUGAUU
667
AAUCAAAA CUGAUGAG GCCGUUAGGC CGAA IGCAACAU
2856





596
UUUGAUUC C UGAAACAU
668
AUGUUUCA CUGAUGAG GCCGUUAGGC CGAA IAAUCAAA
2857





597
UUGAUUCC U GAAACAUG
669
CAUGUUUC CUGAUGAG GCCGUUAGGC CGAA IGAAUCAA
2858





603
CCUGAAAC A UGGAAGAC
670
GUCUUCCA CUGAUGAG GCCGUUAGGC CGAA IUUUCAGG
2859





612
UGGAAGAC A AAGGCUGA
671
UCAGCCUU CUGAUGAG GCCGUUAGGC CGAA IUCUUCCA
2860





618
ACAAAGGC U GACUAUGU
672
ACAUAGUC CUGAUGAG GCCGUUAGGC CGAA ICCUUUGU
2861





622
AGGCUGAC U AUGUGAGA
673
UCUCACAU CUGAUGAG GCCGUUAGGC CGAA IUCAGCCU
2862





632
UGUGAGAC C AAAACUUG
674
CAAGUUUU CUGAUGAG GCCGUUAGGC CGAA IUCUCACA
2863





633
GUGAGACC A AAACUUGA
675
UCAAGUUU CUGAUGAG GCCGUUAGGC CGAA IGUCUCAC
2864





638
ACCAAAAC U UGAGACCU
676
AGGUCUCA CUGAUGAG GCCGUUAGGC CGAA IUUUUGGU
2865





645
CUUGAGAC C UACAAAAA
677
UUUUUGUA CUGAUGAG GCCGUUAGGC CGAA IUCUCAAG
2866





646
UUGAGACC U ACAAAAAU
678
AUUUUUGU CUGAUGAG GCCGUUAGGC CGAA IGUCUCAA
2867





649
AGACCUAC A AAAAUGCU
679
AGCAUUUU CUGAUGAG GCCGUUAGGC CGAA IUAGGUCU
2868





657
AAAAAUGC U GAUGUUCU
680
AGAACAUC CUGAUGAG GCCGUUAGGC CGAA ICAUUUUU
2869





665
UGAUGUUC U GGUUGCUG
681
CAGCAACC CUGAUGAG GCCGUUAGGC CGAA IAACAUCA
2870





672
CUGGUUGC U GAGUCUAC
682
GUAGACUC CUGAUGAG GCCGUUAGGC CGAA ICAACCAG
2871





678
GCUGAGUC U ACUCCUCC
683
GGAGGAGU CUGAUGAG GCCGUUAGGC CGAA IACUCAGC
2872





681
GAGUCUAC U CCUCCAGG
684
CCUGGAGG CUGAUGAG GCCGUUAGGC CGAA IUAGACUC
2873





683
GUCUACUC C UCCAGGUA
685
UACCUGGA CUGAUGAG GCCGUUAGGC CGAA IAGUAGAC
2874





684
UCUACUCC U CCAGGUAA
686
UUACCUGG CUGAUGAG GCCGUUAGGC CGAA IGAGUAGA
2875





686
UACUCCUC C AGGUAAUG
687
CAUUACCU CUGAUGAG GCCGUUAGGC CGAA IAGGAGUA
2876





687
ACUCCUCC A GGUAAUGA
688
UCAUUACC CUGAUGAG GCCGUUAGGC CGAA IGAGGAGU
2877





701
UGAUGAAC C CUACACUG
689
CAGUGUAG CUGAUGAG GCCGUUAGGC CGAA IUUCAUCA
2878





702
GAUGAACC C UACACUGA
690
UCAGUGUA CUGAUGAG GCCGUUAGGC CGAA IGUUCAUC
2879





703
AUGAACCC U ACACUGAG
691
CUCAGUGU CUGAUGAG GCCGUUAGGC CGAA IGGUUCAU
2880





706
AACCCUAC A CUGAGCAG
692
CUGCUCAG CUGAUGAG GCCGUUAGGC CGAA IUAGGGUU
2881





708
CCCUACAC U GAGCAGAU
693
AUCUGCUC CUGAUGAG GCCGUUAGGC CGAA IUGUAGGG
2882





713
CACUGAGC A GAUGGGCA
694
UGCCCAUC CUGAUGAG GCCGUUAGGC CGAA ICUCAGUG
2883





721
AGAUGGGC A ACUGUGGA
695
UCCACAGU CUGAUGAG GCCGUUAGGC CGAA ICCCAUCU
2884





724
UGGGCAAC U GUGGAGAG
696
CUCUCCAC CUGAUGAG GCCGUUAGGC CGAA IUUGCCCA
2885





748
AAAGGAUC C ACCUCACU
697
AGUGAGGU CUGAUGAG GCCGUUAGGC CGAA IAUCCUUU
2886





749
AAGGAUCC A CCUCACUC
698
GAGUGAGG CUGAUGAG GCCGUUAGGC CGAA IGAUCCUU
2887





751
GGAUCCAC C UCACUCCU
699
AGGAGUGA CUGAUGAG GCCGUUAGGC CGAA IUGGAUCC
2888





752
GAUCCACC U CACUCCUG
700
CAGGAGUG CUGAUGAG GCCGUUAGGC CGAA IGUGGAUC
2889





754
UCCACCUC A CUCCUGAU
701
AUCAGGAG CUGAUGAG GCCGUUAGGC CGAA IAGGUGGA
2890





756
CACCUCAC U CCUGAUUU
702
AAAUCAGG CUGAUGAG GCCGUUAGGC CGAA IUGAGGUG
2891





758
CCUCACUC C UGAUUUCA
703
UGAAAUCA CUGAUGAG GCCGUUAGGC CGAA IAGUGAGG
2892





759
CUCACUCC U GAUUUCAU
704
AUGAAAUC CUGAUGAG GCCGUUAGGC CGAA IGAGUGAG
2893





766
CUGAUUUC A UUGCAGGA
705
UCCUGCAA CUGAUGAG GCCGUUAGGC CGAA IAAAUCAG
2894





771
UUCAUUGC A GGAAAAAA
706
UUUUUUCC CUGAUGAG GCCGUUAGGC CGAA ICAAUGAA
2895





786
AAGUUAGC U GAAUAUGG
707
CCAUAUUC CUGAUGAG GCCGUUAGGC CGAA ICUAACUU
2896





797
AUAUGGAC C ACAAGGUA
708
UACCUUGU CUGAUGAG GCCGUUAGGC CGAA IUCCAUAU
2897





798
UAUGGACC A CAAGGUAA
709
UUACCUUG CUGAUGAG GCCGUUAGGC CGAA IGUCCAUA
2898





800
UGGACCAC A AGGUAAGG
710
CCUUACCU CUGAUGAG GCCGUUAGGC CGAA IUGGUCCA
2899





810
GGUAAGGC A UUUGUCCA
711
UGGACAAA CUGAUGAG GCCGUUAGGC CGAA ICCUUACC
2900





817
CAUUUGUC C AUGAGUGG
712
CCACUCAU CUGAUGAG GCCGUUAGGC CGAA IACAAAUG
2901





818
AUUUGUCC A UGAGUGGG
713
CCCACUCA CUGAUGAG GCCGUUAGGC CGAA IGACAAAU
2902





828
GAGUGGGC U CAUCUACG
714
CGUAGAUG CUGAUGAG GCCGUUAGGC CGAA ICCCACUC
2903





830
GUGGGCUC A UCUACGAU
715
AUCGUAGA CUGAUGAG GCCGUUAGGC CGAA IAGCCCAC
2904





833
GGCUCAUC U ACGAUGGG
716
CCCAUCGU CUGAUGAG GCCGUUAGGC CGAA IAUGAGCC
2905





859
ACGAGUAC A AUAAUGAU
717
AUCAUUAU CUGAUGAG GCCGUUAGGC CGAA IUACUCGU
2906





877
AGAAAUUC U ACUUAUCC
718
GGAUAAGU CUGAUGAG GCCGUUAGGC CGAA IAAUUUCU
2907





880
AAUUCUAC U UAUCCAAU
719
AUUGGAUA CUGAUGAG GCCGUUAGGC CGAA IUAGAAUU
2908





885
UACUUAUC C AAUGGAAG
720
CUUCCAUU CUGAUGAG GCCGUUAGGC CGAA IAUAAGUA
2909





886
ACUUAUCC A AUGGAAGA
721
UCUUCCAU CUGAUGAG GCCGUUAGGC CGAA IGAUAAGU
2910





899
AAGAAUAC A AGCAGUAA
722
UUACUGCU CUGAUGAG GCCGUUAGGC CGAA IUAUUCUU
2911





903
AUACAAGC A GUAAGAUG
723
CAUCUUAC CUGAUGAG GCCGUUAGGC CGAA ICUUGUAU
2912





915
AGAUGUUC A GCAGGUAU
724
AUACCUGC CUGAUGAG GCCGUUAGGC CGAA IAACAUCU
2913





918
UGUUCAGC A GGUAUUAC
725
GUAAUACC CUGAUGAG GCCGUUAGGC CGAA ICUGAACA
2914





927
GGUAUUAC U GGUACAAA
726
UUUGUACC CUGAUGAG GCCGUUAGGC CGAA IUAAUACC
2915





933
ACUGGUAC A AAUGUAGU
727
ACUACAUU CUGAUGAG GCCGUUAGGC CGAA IUACCAGU
2916





953
GAAGUGUC A GGGAGGCA
728
UGCCUCCC CUGAUGAG GCCGUUAGGC CGAA IACACUUC
2917





961
AGGGAGGC A GCUGUUAC
729
GUAACAGC CUGAUGAG GCCGUUAGGC CGAA ICCUCCCU
2918





964
GAGGCAGC U GUUACACC
730
GGUGUAAC CUGAUGAG GCCGUUAGGC CGAA ICUGCCUC
2919





970
GCUGUUAC A CCAAAAGA
731
UCUUUUGG CUGAUGAG GCCGUUAGGC CGAA IUAACAGC
2920





972
UGUUACAC C AAAAGAUG
732
CAUCUUUU CUGAUGAG GCCGUUAGGC CGAA IUGUAACA
2921





973
GUUACACC A AAAGAUGC
733
GCAUCUUU CUGAUGAG GCCGUUAGGC CGAA IGUGUAAC
2922





982
AAAGAUGC A CAUUCAAU
734
AUUGAAUG CUGAUGAG GCCGUUAGGC CGAA ICAUCUUU
2923





984
AGAUGCAC A UUCAAUAA
735
UUAUUGAA CUGAUGAG GCCGUUAGGC CGAA IUGCAUCU
2924





988
GCACAUUC A AUAAAGUU
736
AACUUUAU CUGAUGAG GCCGUUAGGC CGAA IAAUGUGC
2925





999
AAAGUUAC A GGACUCUA
737
UAGAGUCC CUGAUGAG GCCGUUAGGC CGAA IUAACUUU
2926





1004
UACAGGAC U CUAUGAAA
738
UUUCAUAG CUGAUGAG GCCGUUAGGC CGAA IUCCUGUA
2927





1006
CAGGACUC U AUGAAAAA
739
UUUUUCAU CUGAUGAG GCCGUUAGGC CGAA IAGUCCUG
2928





1031
GUUUGUUC U CCAAUCCC
740
GGGAUUGG CUGAUGAG GCCGUUAGGC CGAA IAACAAAC
2929





1033
UUGUUCUC C AAUCCCGC
741
GCGGGAUU CUGAUGAG GCCGUUAGGC CGAA IAGAACAA
2930





1034
UGUUCUCC A AUCCCGCC
742
GGCGGGAU CUGAUGAG GCCGUUAGGC CGAA IGAGAACA
2931





1038
CUCCAAUC C CGCCAGAC
743
GUCUGGCG CUGAUGAG GCCGUUAGGC CGAA IAUUGGAG
2932





1039
UCCAAUCC C GCCAGACG
744
CGUCUGGC CUGAUGAG GCCGUUAGGC CGAA IGAUUGGA
2933





1042
AAUCCCGC C AGACGGAG
745
CUCCGUCU CUGAUGAG GCCGUUAGGC CGAA ICGGGAUU
2934





1043
AUCCCGCC A GACGGAGA
746
UCUCCGUC CUGAUGAG GCCGUUAGGC CGAA IGCGGGAU
2935





1056
GAGAAGGC U UCUAUAAU
747
AUUAUAGA CUGAUGAG GCCGUUAGGC CGAA ICCUUCUC
2936





1059
AAGGCUUC U AUAAUGUU
748
AACAUUAU CUGAUGAG GCCGUUAGGC CGAA IAAGCCUU
2937





1071
AUGUUUGC A CAACAUGU
749
ACAUGUUG CUGAUGAG GCCGUUAGGC CGAA ICAAACAU
2938





1073
GUUUGCAC A ACAUGUUG
750
CAACAUGU CUGAUGAG GCCGUUAGGC CGAA IUGCAAAC
2939





1076
UGCACAAC A UGUUGAUU
751
AAUCAACA CUGAUGAG GCCGUUAGGC CGAA IUUGUGCA
2940





1086
GUUGAUUC U AUAGUUGA
752
UCAACUAU CUGAUGAG GCCGUUAGGC CGAA IAAUCAAC
2941





1099
UUGAAUUC U GUACAGAA
753
UUCUGUAC CUGAUGAG GCCGUUAGGC CGAA IAAUUCAA
2942





1104
UUCUGUAC A GAACAAAA
754
UUUUGUUC CUGAUGAG GCCGUUAGGC CGAA IUACAGAA
2943





1109
UACAGAAC A AAACCACA
755
UGUGGUUU CUGAUGAG GCCGUUAGGC CGAA IUUCUGUA
2944





1114
AACAAAAC C ACAACAAA
756
UUUGUUGU CUGAUGAG GCCGUUAGGC CGAA IUUUUGUU
2945





1115
ACAAAACC A CAACAAAG
757
CUUUGUUG CUGAUGAG GCCGUUAGGC CGAA IGUUUUGU
2946





1117
AAAACCAC A ACAAAGAA
758
UUCUUUGU CUGAUGAG GCCGUUAGGC CGAA IUGGUUUU
2947





1120
ACCACAAC A AAGAAGCU
759
AGCUUCUU CUGAUGAG GCCGUUAGGC CGAA IUUGUGGU
2948





1128
AAAGAAGC U CCAAACAA
760
UUGUUUGG CUGAUGAG GCCGUUAGGC CGAA ICUUCUUU
2949





1130
AGAAGCUC C AAACAAGC
761
GCUUGUUU CUGAUGAG GCCGUUAGGC CGAA IAGCUUCU
2950





1131
GAAGCUCC A AACAAGCA
762
UGCUUGUU CUGAUGAG GCCGUUAGGC CGAA IGAGCUUC
2951





1135
CUCCAAAC A AGCAAAAU
763
AUUUUGCU CUGAUGAG GCCGUUAGGC CGAA IUUUGGAG
2952





1139
AAACAAGC A AAAUCAAA
764
UUUGAUUU CUGAUGAG GCCGUUAGGC CGAA ICUUGUUU
2953





1145
GCAAAAUC A AAAAUGCA
765
UGCAUUUU CUGAUGAG GCCGUUAGGC CGAA IAUUUUGC
2954





1153
AAAAAUGC A AUCUCCGA
766
UCGGAGAU CUGAUGAG GCCGUUAGGC CGAA ICAUUUUU
2955





1157
AUGCAAUC U CCGAAGCA
767
UGCUUCGG CUGAUGAG GCCGUUAGGC CGAA IAUUGCAU
2956





1159
GCAAUCUC C GAAGCACA
768
UGUGCUUC CUGAUGAG GCCGUUAGGC CGAA IAGAUUGC
2957





1165
UCCGAAGC A CAUGGGAA
769
UUCCCAUG CUGAUGAG GCCGUUAGGC CGAA ICUUCGGA
2958





1167
CGAAGCAC A UGGGAAGU
770
ACUUCCCA CUGAUGAG GCCGUUAGGC CGAA IUGCUUCG
2959





1180
AAGUGAUC C GUGAUUCU
771
AGAAUCAC CUGAUGAG GCCGUUAGGC CGAA IAUCACUU
2960





1188
CGUGAUUC U GAGGACUU
772
AAGUCCUC CUGAUGAG GCCGUUAGGC CGAA IAAUCACG
2961





1195
CUGAGGAC U UUAAGAAA
773
UUUCUUAA CUGAUGAG GCCGUUAGGC CGAA IUCCUCAG
2962





1206
AAGAAAAC C ACUCCUAU
774
AUAGGAGU CUGAUGAG GCCGUUAGGC CGAA IUUUUCUU
2963





1207
AGAAAACC A CUCCUAUG
775
CAUAGGAG CUGAUGAG GCCGUUAGGC CGAA IGUUUUCU
2964





1209
AAAACCAC U CCUAUGAC
776
GUCAUAGG CUGAUGAG GCCGUUAGGC CGAA IUGGUUUU
2965





1211
AACCACUC C UAUGACAA
777
UUGUCAUA CUGAUGAG GCCGUUAGGC CGAA IAGUGGUU
2966





1212
ACCACUCC U AUGACAAC
778
GUUGUCAU CUGAUGAG GCCGUUAGGC CGAA IGAGUGGU
2967





1218
CCUAUGAC A ACACAGCC
779
GGCUGUGU CUGAUGAG GCCGUUAGGC CGAA IUCAUAGG
2968





1221
AUGACAAC A CAGCCACC
780
GGUGGCUG CUGAUGAG GCCGUUAGGC CGAA IUUGUCAU
2969





1223
GACAACAC A GCCACCAA
781
UUGGUGGC CUGAUGAG GCCGUUAGGC CGAA IUGUUGUC
2970





1226
AACACAGC C ACCAAAUC
782
GAUUUGGU CUGAUGAG GCCGUUAGGC CGAA ICUGUGUU
2971





1227
ACACAGCC A CCAAAUCC
783
GGAUUUGG CUGAUGAG GCCGUUAGGC CGAA IGCUGUGU
2972





1229
ACAGCCAC C AAAUCCCA
784
UGGGAUUU CUGAUGAG GCCGUUAGGC CGAA IUGGCUGU
2973





1230
CAGCCACC A AAUCCCAC
785
GUGGGAUU CUGAUGAG GCCGUUAGGC CGAA IGUGGCUG
2974





1235
ACCAAAUC C CACCUUCU
786
AGAAGGUG CUGAUGAG GCCGUUAGGC CGAA IAUUUGGU
2975





1236
CCAAAUCC C ACCUUCUC
787
GAGAAGGU CUGAUGAG GCCGUUAGGC CGAA IGAUUUGG
2976





1237
CAAAUCCC A CCUUCUCA
788
UGAGAAGG CUGAUGAG GCCGUUAGGC CGAA IGGAUUUG
2977





1239
AAUCCCAC C UUCUCAUU
789
AAUGAGAA CUGAUGAG GCCGUUAGGC CGAA IUGGGAUU
2978





1240
AUCCCACC U UCUCAUUG
790
CAAUGAGA CUGAUGAG GCCGUUAGGC CGAA IGUGGGAU
2979





1243
CCACCUUC U CAUUGCUG
791
CAGCAAUG CUGAUGAG GCCGUUAGGC CGAA IAAGGUGG
2980





1245
ACCUUCUC A UUGCUGCA
792
UGCAGCAA CUGAUGAG GCCGUUAGGC CGAA IAGAAGGU
2981





1250
CUCAUUGC U GCAGAUUG
793
CAAUCUGC CUGAUGAG GCCGUUAGGC CGAA ICAAUGAG
2982





1253
AUUGCUGC A GAUUGGAC
794
GUCCAAUC CUGAUGAG GCCGUUAGGC CGAA ICAGCAAU
2983





1262
GAUUGGAC A AAGAAUUG
795
CAAUUCUU CUGAUGAG GCCGUUAGGC CGAA IUCCAAUC
2984





1282
GUUUAGUC C UUGACAAA
796
UUUGUCAA CUGAUGAG GCCGUUAGGC CGAA IACUAAAC
2985





1283
UUUAGUCC U UGACAAAU
797
AUUUGUCA CUGAUGAG GCCGUUAGGC CGAA IGACUAAA
2986





1288
UCCUUGAC A AAUCUGGA
798
UCCAGAUU CUGAUGAG GCCGUUAGGC CGAA IUCAAGGA
2987





1293
GACAAAUC U GGAAGCAU
799
AUGCUUCC CUGAUGAG GCCGUUAGGC CGAA IAUUUGUC
2988





1300
CUGGAAGC A UGGCGACU
800
AGUCGCCA CUGAUGAG GCCGUUAGGC CGAA ICUUCCAG
2989





1308
AUGGCGAC U GGUAACCG
801
CGGUUACC CUGAUGAG GCCGUUAGGC CGAA IUCGCCAU
2990





1315
CUGGUAAC C GCCUCAAU
802
AUUGAGGC CUGAUGAG GCCGUUAGGC CGAA IUUACCAG
2991





1318
GUAACCGC C UCAAUCGA
803
UCGAUUGA CUGAUGAG GCCGUUAGGC CGAA ICGGUUAC
2992





1319
UAACCGCC U CAAUCGAC
804
GUCGAUUG CUGAUGAG GCCGUUAGGC CGAA IGCGGUUA
2993





1321
ACCGCCUC A AUCGACUG
805
CAGUCGAU CUGAUGAG GCCGUUAGGC CGAA IAGGCGGU
2994





1328
CAAUCGAC U GAAUCAAG
806
CUUGAUUC CUGAUGAG GCCGUUAGGC CGAA IUCGAUUG
2995





1334
ACUGAAUC A AGCAGGCC
807
GGCCUGCU CUGAUGAG GCCGUUAGGC CGAA IAUUCAGU
2996





1338
AAUCAAGC A GGCCAGCU
808
AGCUGGCC CUGAUGAG GCCGUUAGGC CGAA ICUUGAUU
2997





1342
AAGCAGGC C AGCUUUUC
809
GAAAAGCU CUGAUGAG GCCGUUAGGC CGAA ICCUGCUU
2998





1343
AGCAGGCC A GCUUUUCC
810
GGAAAAGC CUGAUGAG GCCGUUAGGC CGAA IGCCUGCU
2999





1346
AGGCCAGC U UUUCCUGC
811
GCAGGAAA CUGAUGAG GCCGUUAGGC CGAA ICUGGCCU
3000





1351
AGCUUUUC C UGCUGCAG
812
CUGCAGCA CUGAUGAG GCCGUUAGGC CGAA IAAAAGCU
3001





1352
GCUUUUCC U GCUGCAGA
813
UCUGCAGC CUGAUGAG GCCGUUAGGC CGAA IGAAAAGC
3002





1355
UUUCCUGC U GCAGACAG
814
CUGUCUGC CUGAUGAG GCCGUUAGGC CGAA ICAGGAAA
3003





1358
CCUGCUGC A GACAGUUG
815
CAACUGUC CUGAUGAG GCCGUUAGGC CGAA ICAGCAGG
3004





1362
CUGCAGAC A GUUGAGCU
816
AGCUCAAC CUGAUGAG GCCGUUAGGC CGAA IUCUGCAG
3005





1370
AGUUGAGC U GGGGUCCU
817
AGGACCCC CUGAUGAG GCCGUUAGGC CGAA ICUCAACU
3006





1377
CUGGGGUC C UGGGUUGG
818
CCAACCCA CUGAUGAG GCCGUUAGGC CGAA IACCCCAG
3007





1378
UGGGGUCC U GGGUUGGG
819
CCCAACCC CUGAUGAG GCCGUUAGGC CGAA IGACCCCA
3008





1395
AUGGUGAC A UUUGACAG
820
CUGUCAAA CUGAUGAG GCCGUUAGGC CGAA IUCACCAU
3009





1402
CAUUUGAC A GUGCUGCC
821
GGCAGCAC CUGAUGAG GCCGUUAGGC CGAA IUCAAAUG
3010





1407
GACAGUGC U GCCCAUGU
822
ACAUGGGC CUGAUGAG GCCGUUAGGC CGAA ICACUGUC
3011





1410
AGUGCUGC C CAUGUACA
823
UGUACAUG CUGAUGAG GCCGUUAGGC CGAA ICAGCACU
3012





1411
GUGCUGCC C AUGUACAA
824
UUGUACAU CUGAUGAG GCCGUUAGGC CGAA IGCAGCAC
3013





1412
UGCUGCCC A UGUACAAA
825
UUUGUACA CUGAUGAG GCCGUUAGGC CGAA IGGCAGCA
3014





1418
CCAUGUAC A AAGUGAAC
826
GUUCACUU CUGAUGAG GCCGUUAGGC CGAA IUACAUGG
3015





1427
AAGUGAAC U CAUACAGA
827
UCUGUAUG CUGAUGAG GCCGUUAGGC CGAA IUUCACUU
3016





1429
GUGAACUC A UACAGAUA
828
UAUCUGUA CUGAUGAG GCCGUUAGGC CGAA IAGUUCAC
3017





1433
ACUCAUAC A GAUAAACA
829
UGUUUAUC CUGAUGAG GCCGUUAGGC CGAA IUAUGAGU
3018





1441
AGAUAAAC A GUGGCAGU
830
ACUGCCAC CUGAUGAG GCCGUUAGGC CGAA IUUUAUCU
3019





1447
ACAGUGGC A GUGACAGG
831
CCUGUCAC CUGAUGAG GCCGUUAGGC CGAA ICCACUGU
3020





1453
GCAGUGAC A GGGACACA
832
UGUGUCCC CUGAUGAG GCCGUUAGGC CGAA IUCACUGC
3021





1459
ACAGGGAC A CACUCGCC
833
GGCGAGUG CUGAUGAG GCCGUUAGGC CGAA IUCCCUGU
3022





1461
AGGGACAC A CUCGCCAA
834
UUGGCGAG CUGAUGAG GCCGUUAGGC CGAA IUGUCCCU
3023





1463
GGACACAC U CGCCAAAA
835
UUUUGGCG CUGAUGAG GCCGUUAGGC CGAA IUGUGUCC
3024





1467
ACACUCGC C AAAAGAUU
836
AAUCUUUU CUGAUGAG GCCGUUAGGC CGAA ICGAGUGU
3025





1468
CACUCGCC A AAAGAUUA
837
UAAUCUUU CUGAUGAG GCCGUUAGGC CGAA IGCGAGUG
3026





1478
AAGAUUAC C UGCAGCAG
838
CUGCUGCA CUGAUGAG GCCGUUAGGC CGAA IUAAUCUU
3027





1479
AGAUUACC U GCAGCAGC
839
GCUGCUGC CUGAUGAG GCCGUUAGGC CGAA IGUAAUCU
3028





1482
UUACCUGC A GCAGCUUC
840
GAAGCUGC CUGAUGAG GCCGUUAGGC CGAA ICAGGUAA
3029





1485
CCUGCAGC A GCUUCAGG
841
CCUGAAGC CUGAUGAG GCCGUUAGGC CGAA ICUGCAGG
3030





1488
GCAGCAGC U UCAGGAGG
842
CCUCCUGA CUGAUGAG GCCGUUAGGC CGAA ICUGCUGC
3031





1491
GCAGCUUC A GGAGGGAC
843
GUCCCUCC CUGAUGAG GCCGUUAGGC CGAA IAAGCUGC
3032





1503
GGGACGUC C AUCUGCAG
844
CUGCAGAU CUGAUGAG GCCGUUAGGC CGAA IACGUCCC
3033





1504
GGACGUCC A UCUGCAGC
845
GCUGCAGA CUGAUGAG GCCGUUAGGC CGAA IGACGUCC
3034





1507
CGUCCAUC U GCAGCGGG
846
CCCGCUGC CUGAUGAG GCCGUUAGGC CGAA IAUGGACG
3035





1510
CCAUCUGC A GCGGGCUU
847
AAGCCCGC CUGAUGAG GCCGUUAGGC CGAA ICAGAUGG
3036





1517
CAGCGGGC U UCGAUCGG
848
CCGAUCGA CUGAUGAG GCCGUUAGGC CGAA ICCCGCUG
3037





1527
CGAUCGGC A UUUACUGU
849
ACAGUAAA CUGAUGAG GCCGUUAGGC CGAA ICCGAUCG
3038





1533
GCAUUUAC U GUGAUUAG
850
CUAAUCAC CUGAUGAG GCCGUUAGGC CGAA IUAAAUGC
3039





1553
GAAAUAUC C AACUGAUG
851
CAUCAGUU CUGAUGAG GCCGUUAGGC CGAA IAUAUUUC
3040





1554
AAAUAUCC A ACUGAUGG
852
CCAUCAGU CUGAUGAG GCCGUUAGGC CGAA IGAUAUUU
3041





1557
UAUCCAAC U GAUGGAUC
853
GAUCCAUC CUGAUGAG GCCGUUAGGC CGAA IUUGGAUA
3042





1566
GAUGGAUC U GAAAUUGU
854
ACAAUUUC CUGAUGAG GCCGUUAGGC CGAA IAUCCAUC
3043





1577
AAUUGUGC U GCUGACGG
855
CCGUCAGC CUGAUGAG GCCGUUAGGC CGAA ICACAAUU
3044





1580
UGUGCUGC U GACGGAUG
856
CAUCCGUC CUGAUGAG GCCGUUAGGC CGAA ICAGCACA
3045





1597
GGGAAGAC A ACACUAUA
857
UAUAGUGU CUGAUGAG GCCGUUAGGC CGAA IUCUUCCC
3046





1600
AAGACAAC A CUAUAAGU
858
ACUUAUAG CUGAUGAG GCCGUUAGGC CGAA IUUGUCUU
3047





1602
GACAACAC U AUAAGUGG
859
CCACUUAU CUGAUGAG GCCGUUAGGC CGAA IUGUUGUC
3048





1615
GUGGGUGC U UUAACGAG
860
CUCGUUAA CUGAUGAG GCCGUUAGGC CGAA ICACCCAC
3049





1627
ACGAGGUC A AACAAAGU
861
ACUUUGUU CUGAUGAG GCCGUUAGGC CGAA IACCUCGU
3050





1631
GGUCAAAC A AAGUGGUG
862
CACCACUU CUGAUGAG GCCGUUAGGC CGAA IUUUGACC
3051





1641
AGUGGUGC C AUCAUCCA
863
UGGAUGAU CUGAUGAG GCCGUUAGGC CGAA ICACCACU
3052





1642
GUGGUGCC A UCAUCCAC
864
GUGGAUGA CUGAUGAG GCCGUUAGGC CGAA IGCACCAC
3053





1645
GUGCCAUC A UCCACACA
865
UGUGUGGA CUGAUGAG GCCGUUAGGC CGAA IAUGGCAC
3054





1648
CCAUCAUC C ACACAGUC
866
GACUGUGU CUGAUGAG GCCGUUAGGC CGAA IAUGAUGG
3055





1649
CAUCAUCC A CACAGUCG
867
CGACUGUG CUGAUGAG GCCGUUAGGC CGAA IGAUGAUG
3056





1651
UCAUCCAC A CAGUCGCU
868
AGCGACUG CUGAUGAG GCCGUUAGGC CGAA IUGGAUGA
3057





1653
AUCCACAC A GUCGCUUU
869
AAAGCGAC CUGAUGAG GCCGUUAGGC CGAA IUGUGGAU
3058





1659
ACAGUCGC U UUGGGGCC
870
GGCCCCAA CUGAUGAG GCCGUUAGGC CGAA ICGACUGU
3059





1667
UUUGGGGC C CUCUGCAG
871
CUGCAGAG CUGAUGAG GCCGUUAGGC CGAA ICCCCAAA
3060





1668
UUGGGGCC C UCUGCAGC
872
GCUGCAGA CUGAUGAG GCCGUUAGGC CGAA IGCCCCAA
3061





1669
UGGGGCCC U CUGCAGCU
873
AGCUGCAG CUGAUGAG GCCGUUAGGC CGAA IGGCCCCA
3062





1671
GGGCCCUC U GCAGCUCA
874
UGAGCUGC CUGAUGAG GCCGUUAGGC CGAA IAGGGCCC
3063





1674
CCCUCUGC A GCUCAAGA
875
UCUUGAGC CUGAUGAG GCCGUUAGGC CGAA ICAGAGGG
3064





1677
UCUGCAGC U CAAGAACU
876
AGUUCUUG CUGAUGAG GCCGUUAGGC CGAA ICUGCAGA
3065





1679
UGCAGCUC A AGAACUAG
877
CUAGUUCU CUGAUGAG GCCGUUAGGC CGAA IAGCUGCA
3066





1685
UCAAGAAC U AGAGGAGC
878
GCUCCUCU CUGAUGAG GCCGUUAGGC CGAA IUUCUUGA
3067





1694
AGAGGAGC U GUCCAAAA
879
UUUUGGAC CUGAUGAG GCCGUUAGGC CGAA ICUCCUCU
3068





1698
GAGCUGUC C AAAAUGAC
880
GUCAUUUU CUGAUGAG GCCGUUAGGC CGAA IACAGCUC
3069





1699
AGCUGUCC A AAAUGACA
881
UGUCAUUU CUGAUGAG GCCGUUAGGC CGAA IGACAGCU
3070





1707
AAAAUGAC A GGAGGUUU
882
AAACCUCC CUGAUGAG GCCGUUAGGC CGAA IUCAUUUU
3071





1718
AGGUUUAC A GACAUAUG
883
CAUAUGUC CUGAUGAG GCCGUUAGGC CGAA IUAAACCU
3072





1722
UUACAGAC A UAUGCUUC
884
GAAGCAUA CUGAUGAG GCCGUUAGGC CGAA IUCUGUAA
3073





1728
ACAUAUGC U UCAGAUCA
885
UGAUCUGA CUGAUGAG GCCGUUAGGC CGAA ICAUAUGU
3074





1731
UAUGCUUC A GAUCAAGU
886
ACUUGAUC CUGAUGAG GCCGUUAGGC CGAA IAAGCAUA
3075





1736
UUCAGAUC A AGUUCAGA
887
UCUGAACU CUGAUGAG GCCGUUAGGC CGAA IAUCUGAA
3076





1742
UCAAGUUC A GAACAAUG
888
CAUUGUUC CUGAUGAG GCCGUUAGGC CGAA IAACUUGA
3077





1747
UUCAGAAC A AUGGCCUC
889
GAGGCCAU CUGAUGAG GCCGUUAGGC CGAA IUUCUGAA
3078





1753
ACAAUGGC C UCAUUGAU
890
AUCAAUGA CUGAUGAG GCCGUUAGGC CGAA ICCAUUGU
3079





1754
CAAUGGCC U CAUUGAUG
891
CAUCAAUG CUGAUGAG GCCGUUAGGC CGAA IGCCAUUG
3080





1756
AUGGCCUC A UUGAUGCU
892
AGCAUCAA CUGAUGAG GCCGUUAGGC CGAA IAGGCCAU
3081





1764
AUUGAUGC U UUUGGGGC
893
GCCCCAAA CUGAUGAG GCCGUUAGGC CGAA ICAUCAAU
3082





1773
UUUGGGGC C CUUUCAUC
894
GAUGAAAG CUGAUGAG GCCGUUAGGC CGAA ICCCCAAA
3083





1774
UUGGGGCC C UUUCAUCA
895
UGAUGAAA CUGAUGAG GCCGUUAGGC CGAA IGCCCCAA
3084





1775
UGGGGCCC U UUCAUCAG
896
CUGAUGAA CUGAUGAG GCCGUUAGGC CGAA IGGCCCCA
3085





1779
GCCCUUUC A UCAGGAAA
897
UUUCCUGA CUGAUGAG GCCGUUAGGC CGAA IAAAGGGC
3086





1782
CUUUCAUC A GGAAAUGG
898
CCAUUUCC CUGAUGAG GCCGUUAGGC CGAA IAUGAAAG
3087





1794
AAUGGAGC U GUCUCUCA
899
UGAGAGAC CUGAUGAG GCCGUUAGGC CGAA ICUCCAUU
3088





1798
GAGCUGUC U CUCAGCGC
900
GCGCUGAG CUGAUGAG GCCGUUAGGC CGAA IACAGCUC
3089





1800
GCUGUCUC U CAGCGCUC
901
GAGCGCUG CUGAUGAG GCCGUUAGGC CGAA IAGACAGC
3090





1802
UGUCUCUC A GCGCUCCA
902
UGGAGCGC CUGAUGAG GCCGUUAGGC CGAA IAGAGACA
3091





1807
CUCAGCGC U CCAUCCAG
903
CUGGAUGG CUGAUGAG GCCGUUAGGC CGAA ICGCUGAG
3092





1809
CAGCGCUC C AUCCAGCU
904
AGCUGGAU CUGAUGAG GCCGUUAGGC CGAA IAGCGCUG
3093





1810
AGCGCUCC A UCCAGCUU
905
AAGCUGGA CUGAUGAG GCCGUUAGGC CGAA IGAGCGCU
3094





1813
GCUCCAUC C AGCUUGAG
906
CUCAAGCU CUGAUGAG GCCGUUAGGC CGAA IAUGGAGC
3095





1814
CUCCAUCC A GCUUGAGA
907
UCUCAAGC CUGAUGAG GCCGUUAGGC CGAA IGAUGGAG
3096





1817
CAUCCAGC U UGAGAGUA
908
UACUCUCA CUGAUGAG GCCGUUAGGC CGAA ICUGGAUG
3097





1836
GGAUUAAC C CUCCAGAA
909
UUCUGGAG CUGAUGAG GCCGUUAGGC CGAA IUUAAUCC
3098





1837
GAUUAACC C UCCAGAAC
910
GUUCUGGA CUGAUGAG GCCGUUAGGC CGAA IGUUAAUC
3099





1838
AUUAACCC U CCAGAACA
911
UGUUCUGG CUGAUGAG GCCGUUAGGC CGAA IGGUUAAU
3100





1840
UAACCCUC C AGAACAGC
912
GCUGUUCU CUGAUGAG GCCGUUAGGC CGAA IAGGGUUA
3101





1841
AACCCUCC A GAACAGCC
913
GGCUGUUC CUGAUGAG GCCGUUAGGC CGAA IGAGGGUU
3102





1846
UCCAGAAC A GCCAGUGG
914
CCACUGGC CUGAUGAG GCCGUUAGGC CGAA IUUCUGGA
3103





1849
AGAACAGC C AGUGGAUG
915
CAUCCACU CUGAUGAG GCCGUUAGGC CGAA ICUGUUCU
3104





1850
GAACAGCC A GUGGAUGA
916
UCAUCCAC CUGAUGAG GCCGUUAGGC CGAA IGCUGUUC
3105





1864
UGAAUGGC A CAGUGAUC
917
GAUCACUG CUGAUGAG GCCGUUAGGC CGAA ICCAUUCA
3106





1866
AAUGGCAC A GUGAUCGU
918
ACGAUCAC CUGAUGAG GCCGUUAGGC CGAA IUGCCAUU
3107





1879
UCGUGGAC A GCACCGUG
919
CACGGUGC CUGAUGAG GCCGUUAGGC CGAA IUCCACGA
3108





1882
UGGACAGC A CCGUGGGA
920
UCCCACGG CUGAUGAG GCCGUUAGGC CGAA ICUGUCCA
3109





1884
GACAGCAC C GUGGGAAA
921
UUUCCCAC CUGAUGAG GCCGUUAGGC CGAA IUGCUGUC
3110





1897
GAAAGGAC A CUUUGUUU
922
AAACAAAG CUGAUGAG GCCGUUAGGC CGAA IUCCUUUC
3111





1899
AAGGACAC U UUGUUUCU
923
AGAAACAA CUGAUGAG GCCGUUAGGC CGAA IUGUCCUU
3112





1907
UUUGUUUC U UAUCACCU
924
AGGUGAUA CUGAUGAG GCCGUUAGGC CGAA IAAACAAA
3113





1912
UUCUUAUC A CCUGGACA
925
UGUCCAGG CUGAUGAG GCCGUUAGGC CGAA IAUAAGAA
3114





1914
CUUAUCAC C UGGACAAC
926
GUUGUCCA CUGAUGAG GCCGUUAGGC CGAA IUGAUAAG
3115





1915
UUAUCACC U GGACAACG
927
CGUUGUCC CUGAUGAG GCCGUUAGGC CGAA IGUGAUAA
3116





1920
ACCUGGAC A ACGCAGCC
928
GGCUGCGU CUGAUGAG GCCGUUAGGC CGAA IUCCAGGU
3117





1925
GACAACGC A GCCUCCCC
929
GGGGAGGC CUGAUGAG GCCGUUAGGC CGAA ICGUUGUC
3118





1928
AACGCAGC C UCCCCAAA
930
UUUGGGGA CUGAUGAG GCCGUUAGGC CGAA ICUGCGUU
3119





1929
ACGCAGCC U CCCCAAAU
931
AUUUGGGG CUGAUGAG GCCGUUAGGC CGAA IGCUGCGU
3120





1931
GCAGCCUC C CCAAAUCC
932
GGAUUUGG CUGAUGAG GCCGUUAGGC CGAA IAGGCUGC
3121





1932
CAGCCUCC C CAAAUCCU
933
AGGAUUUG CUGAUGAG GCCGUUAGGC CGAA IGAGGCUG
3122





1933
AGCCUCCC C AAAUCCUU
934
AAGGAUUU CUGAUGAG GCCGUUAGGC CGAA IGGAGGCU
3123





1934
GCCUCCCC A AAUCCUUC
935
GAAGGAUU CUGAUGAG GCCGUUAGGC CGAA IGGGAGGC
3124





1939
CCCAAAUC C UUCUCUGG
936
CCAGAGAA CUGAUGAG GCCGUUAGGC CGAA IAUUUGGG
3125





1940
CCAAAUCC U UCUCUGGG
937
CCCAGAGA CUGAUGAG GCCGUUAGGC CGAA IGAUUUGG
3126





1943
AAUCCUUC U CUGGGAUC
938
GAUCCCAG CUGAUGAG GCCGUUAGGC CGAA IAAGGAUU
3127





1945
UCCUUCUC U GGGAUCCC
939
GGGAUCCC CUGAUGAG GCCGUUAGGC CGAA IAGAAGGA
3128





1952
CUGGGAUC C CAGUGGAC
940
GUCCACUG CUGAUGAG GCCGUUAGGC CGAA IAUCCCAG
3129





1953
UGGGAUCC C AGUGGACA
941
UGUCCACU CUGAUGAG GCCGUUAGGC CGAA IGAUCCCA
3130





1954
GGGAUCCC A GUGGACAG
942
CUGUCCAC CUGAUGAG GCCGUUAGGC CGAA IGGAUCCC
3131





1961
CAGUGGAC A GAAGCAAG
943
CUUGCUUC CUGAUGAG GCCGUUAGGC CGAA IUCCACUG
3132





1967
ACAGAAGC A AGGUGGCU
944
AGCCACCU CUGAUGAG GCCGUUAGGC CGAA ICUUCUGU
3133





1975
AAGGUGGC U UUGUAGUG
945
CACUACAA CUGAUGAG GCCGUUAGGC CGAA ICCACCUU
3134





1987
UAGUGGAC A AAAACACC
946
GGUGUUUU CUGAUGAG GCCGUUAGGC CGAA IUCCACUA
3135





1993
ACAAAAAC A CCAAAAUG
947
CAUUUUGG CUGAUGAG GCCGUUAGGC CGAA IUUUUUGU
3136





1995
AAAAACAC C AAAAUGGC
948
GCCAUUUU CUGAUGAG GCCGUUAGGC CGAA IUGUUUUU
3137





1996
AAAACACC A AAAUGGCC
949
GGCCAUUU CUGAUGAG GCCGUUAGGC CGAA IGUGUUUU
3138





2004
AAAAUGGC C UACCUCCA
950
UGGAGGUA CUGAUGAG GCCGUUAGGC CGAA ICCAUUUU
3139





2005
AAAUGGCC U ACCUCCAA
951
UUGGAGGU CUGAUGAG GCCGUUAGGC CGAA IGCCAUUU
3140





2008
UGGCCUAC C UCCAAAUC
952
GAUUUGGA CUGAUGAG GCCGUUAGGC CGAA IUAGGCCA
3141





2009
GGCCUACC U CCAAAUCC
953
GGAUUUGG CUGAUGAG GCCGUUAGGC CGAA IGUAGGCC
3142





2011
CCUACCUC C AAAUCCCA
954
UGGGAUUU CUGAUGAG GCCGUUAGGC CGAA IAGGUAGG
3143





2012
CUACCUCC A AAUCCCAG
955
CUGGGAUU CUGAUGAG GCCGUUAGGC CGAA IGAGGUAG
3144





2017
UCCAAAUC C CAGGCAUU
956
AAUGCCUG CUGAUGAG GCCGUUAGGC CGAA IAUUUGGA
3145





2018
CCAAAUCC C AGGCAUUG
957
CAAUGCCU CUGAUGAG GCCGUUAGGC CGAA IGAUUUGG
3146





2019
CAAAUCCC A GGCAUUGC
958
GCAAUGCC CUGAUGAG GCCGUUAGGC CGAA IGGAUUUG
3147





2023
UCCCAGGC A UUGCUAAG
959
CUUAGCAA CUGAUGAG GCCGUUAGGC CGAA ICCUGGGA
3148





2028
GGCAUUGC U AAGGUUGG
960
CCAACCUU CUGAUGAG GCCGUUAGGC CGAA ICAAUGCC
3149





2038
AGGUUGGC A CUUGGAAA
961
UUUCCAAG CUGAUGAG GCCGUUAGGC CGAA ICCAACCU
3150





2040
GUUGGCAC U UGGAAAUA
962
UAUUUCCA CUGAUGAG GCCGUUAGGC CGAA IUGCCAAC
3151





2050
GGAAAUAC A GUCUGCAA
963
UUGCAGAC CUGAUGAG GCCGUUAGGC CGAA IUAUUUCC
3152





2054
AUACAGUC U GCAAGCAA
964
UUGCUUGC CUGAUGAG GCCGUUAGGC CGAA IACUGUAU
3153





2057
CAGUCUGC A AGCAAGCU
965
AGCUUGCU CUGAUGAG GCCGUUAGGC CGAA ICAGACUG
3154





2061
CUGCAAGC A AGCUCACA
966
UGUGAGCU CUGAUGAG GCCGUUAGGC CGAA ICUUGCAG
3155





2065
AAGCAAGC U CACAAACC
967
GGUUUGUG CUGAUGAG GCCGUUAGGC CGAA ICUUGCUU
3156





2067
GCAAGCUC A CAAACCUU
968
AAGGUUUG CUGAUGAG GCCGUUAGGC CGAA IAGCUUGC
3157





2069
AAGCUCAC A AACCUUGA
969
UCAAGGUU CUGAUGAG GCCGUUAGGC CGAA IUGAGCUU
3158





2073
UCACAAAC C UUGACCCU
970
AGGGUCAA CUGAUGAG GCCGUUAGGC CGAA IUUUGUGA
3159





2074
CACAAACC U UGACCCUG
971
CAGGGUCA CUGAUGAG GCCGUUAGGC CGAA IGUUUGUG
3160





2079
ACCUUGAC C CUGACUGU
972
ACAGUCAG CUGAUGAG GCCGUUAGGC CGAA IUCAAGGU
3161





2080
CCUUGACC C UGACUGUC
973
GACAGUCA CUGAUGAG GCCGUUAGGC CGAA IGUCAAGG
3162





2081
CUUGACCC U GACUGUCA
974
UGACAGUC CUGAUGAG GCCGUUAGGC CGAA IGGUCAAG
3163





2085
ACCCUGAC U GUCACGUC
975
GACGUGAC CUGAUGAG GCCGUUAGGC CGAA IUCAGGGU
3164





2089
UGACUGUC A CGUCCCGU
976
ACGGGACG CUGAUGAG GCCGUUAGGC CGAA IACAGUCA
3165





2094
GUCACGUC C CGUGCGUC
977
GACGCACG CUGAUGAG GCCGUUAGGC CGAA IACGUGAC
3166





2095
UCACGUCC C GUGCGUCC
978
GGACGCAC CUGAUGAG GCCGUUAGGC CGAA IGACGUGA
3167





2103
CGUGCGUC C AAUGCUAC
979
GUAGCAUU CUGAUGAG GCCGUUAGGC CGAA IACGCACG
3168





2104
GUGCGUCC A AUGCUACC
980
GGUAGCAU CUGAUGAG GCCGUUAGGC CGAA IGACGCAC
3169





2109
UCCAAUGC U ACCCUGCC
981
GGCAGGGU CUGAUGAG GCCGUUAGGC CGAA ICAUUGGA
3170





2112
AAUGCUAC C CUGCCUCC
982
GGAGGCAG CUGAUGAG GCCGUUAGGC CGAA IUAGCAUU
3171





2113
AUGCUACC C UGCCUCCA
983
UGGAGGCA CUGAUGAG GCCGUUAGGC CGAA IGUAGCAU
3172





2114
UGCUACCC U GCCUCCAA
984
UUGGAGGC CUGAUGAG GCCGUUAGGC CGAA IGGUAGCA
3173





2117
UACCCUGC C UCCAAUUA
985
UAAUUGGA CUGAUGAG GCCGUUAGGC CGAA ICAGGGUA
3174





2118
ACCCUGCC U CCAAUUAC
986
GUAAUUGG CUGAUGAG GCCGUUAGGC CGAA IGCAGGGU
3175





2120
CCUGCCUC C AAUUACAG
987
CUGUAAUU CUGAUGAG GCCGUUAGGC CGAA IAGGCAGG
3176





2121
CUGCCUCC A AUUACAGU
988
ACUGUAAU CUGAUGAG GCCGUUAGGC CGAA IGAGGCAG
3177





2127
CCAAUUAC A GUGACUUC
989
GAAGUCAC CUGAUGAG GCCGUUAGGC CGAA IUAAUUGG
3178





2133
ACAGUGAC U UCCAAAAC
990
GUUUUGGA CUGAUGAG GCCGUUAGGC CGAA IUCACUGU
3179





2136
GUGACUUC C AAAACGAA
991
UUCGUUUU CUGAUGAG GCCGUUAGGC CGAA IAAGUCAC
3180





2137
UGACUUCC A AAACGAAC
992
GUUCGUUU CUGAUGAG GCCGUUAGGC CGAA IGAAGUCA
3181





2146
AAACGAAC A AGGACACC
993
GGUGUCCU CUGAUGAG GCCGUUAGGC CGAA IUUCGUUU
3182





2152
ACAAGGAC A CCAGCAAA
994
UUUGCUGG CUGAUGAG GCCGUUAGGC CGAA IUCCUUGU
3183





2154
AAGGACAC C AGCAAAUU
995
AAUUUGCU CUGAUGAG GCCGUUAGGC CGAA IUGUCCUU
3184





2155
AGGACACC A GCAAAUUC
996
GAAUUUGC CUGAUGAG GCCGUUAGGC CGAA IGUGUCCU
3185





2158
ACACCAGC A AAUUCCCC
997
GGGGAAUU CUGAUGAG GCCGUUAGGC CGAA ICUGGUGU
3186





2164
GCAAAUUC C CCAGCCCU
998
AGGGCUGG CUGAUGAG GCCGUUAGGC CGAA IAAUUUGC
3187





2165
CAAAUUCC C CAGCCCUC
999
GAGGGCUG CUGAUGAG GCCGUUAGGC CGAA IGAAUUUG
3188





2166
AAAUUCCC C AGCCCUCU
1000
AGAGGGCU CUGAUGAG GCCGUUAGGC CGAA IGGAAUUU
3189





2167
AAUUCCCC A GCCCUCUG
1001
CAGAGGGC CUGAUGAG GCCGUUAGGC CGAA IGGGAAUU
3190





2170
UCCCCAGC C CUCUGGUA
1002
UACCAGAG CUGAUGAG GCCGUUAGGC CGAA ICUGGGGA
3191





2171
CCCCAGCC C UCUGGUAG
1003
CUACCAGA CUGAUGAG GCCGUUAGGC CGAA IGCUGGGG
3192





2172
CCCAGCCC U CUGGUAGU
1004
ACUACCAG CUGAUGAG GCCGUUAGGC CGAA IGGCUGGG
3193





2174
CAGCCCUC U GGUAGUUU
1005
AAACUACC CUGAUGAG GCCGUUAGGC CGAA IAGGGCUG
3194





2187
GUUUAUGC A AAUAUUCG
1006
CGAAUAUU CUGAUGAG GCCGUUAGGC CGAA ICAUAAAC
3195





2197
AUAUUCGC C AAGGAGCC
1007
GGCUCCUU CUGAUGAG GCCGUUAGGC CGAA ICGAAUAU
3196





2198
UAUUCGCC A AGGAGCCU
1008
AGGCUCCU CUGAUGAG GCCGUUAGGC CGAA IGCGAAUA
3197





2205
CAAGGAGC C UCCCCAAU
1009
AUUGGGGA CUGAUGAG GCCGUUAGGC CGAA ICUCCUUG
3198





2206
AAGGAGCC U CCCCAAUU
1010
AAUUGGGG CUGAUGAG GCCGUUAGGC CGAA IGCUCCUU
3199





2208
GGAGCCUC C CCAAUUCU
1011
AGAAUUGG CUGAUGAG GCCGUUAGGC CGAA IAGGCUCC
3200





2209
GAGCCUCC C CAAUUCUC
1012
GAGAAUUG CUGAUGAG GCCGUUAGGC CGAA IGAGGCUC
3201





2210
AGCCUCCC C AAUUCUCA
1013
UGAGAAUU CUGAUGAG GCCGUUAGGC CGAA IGGAGGCU
3202





2211
GCCUCCCC A AUUCUCAG
1014
CUGAGAAU CUGAUGAG GCCGUUAGGC CGAA IGGGAGGC
3203





2216
CCCAAUUC U CAGGGCCA
1015
UGGCCCUG CUGAUGAG GCCGUUAGGC CGAA IAAUUGGG
3204





2218
CAAUUCUC A GGGCCAGU
1016
ACUGGCCC CUGAUGAG GCCGUUAGGC CGAA IAGAAUUG
3205





2223
CUCAGGGC C AGUGUCAC
1017
GUGACACU CUGAUGAG GCCGUUAGGC CGAA ICCCUGAG
3206





2224
UCAGGGCC A GUGUCACA
1018
UGUGACAC CUGAUGAG GCCGUUAGGC CGAA IGCCCUGA
3207





2230
CCAGUGUC A CAGCCCUG
1019
CAGGGCUG CUGAUGAG GCCGUUAGGC CGAA IACACUGG
3208





2232
AGUGUCAC A GCCCUGAU
1020
AUCAGGGC CUGAUGAG GCCGUUAGGC CGAA IUGACACU
3209





2235
GUCACAGC C CUGAUUGA
1021
UCAAUCAG CUGAUGAG GCCGUUAGGC CGAA ICUGUGAC
3210





2236
UCACAGCC C UGAUUGAA
1022
UUCAAUCA CUGAUGAG GCCGUUAGGC CGAA IGCUGUGA
3211





2237
CACAGCCC U GAUUGAAU
1023
AUUCAAUC CUGAUGAG GCCGUUAGGC CGAA IGGCUGUG
3212





2247
AUUGAAUC A GUGAAUGG
1024
CCAUUCAC CUGAUGAG GCCGUUAGGC CGAA IAUUCAAU
3213





2262
GGAAAAAC A GUUACCUU
1025
AAGGUAAC CUGAUGAG GCCGUUAGGC CGAA IUUUUUCC
3214





2268
ACAGUUAC C UUGGAACU
1026
AGUUCCAA CUGAUGAG GCCGUUAGGC CGAA IUAACUGU
3215





2269
CAGUUACC U UGGAACUA
1027
UAGUUCCA CUGAUGAG GCCGUUAGGC CGAA IGUAACUG
3216





2276
CUUGGAAC U ACUGGAUA
1028
UAUCCAGU CUGAUGAG GCCGUUAGGC CGAA IUUCCAAG
3217





2279
GGAACUAC U GGAUAAUG
1029
CAUUAUCC CUGAUGAG GCCGUUAGGC CGAA IUAGUUCC
3218





2292
AAUGGAGC A GGUGCUGA
1030
UCAGCACC CUGAUGAG GCCGUUAGGC CGAA ICUCCAUU
3219





2298
GCAGGUGC U GAUGCUAC
1031
GUAGCAUC CUGAUGAG GCCGUUAGGC CGAA ICACCUGC
3220





2304
GCUGAUGC U ACUAAGGA
1032
UCCUUAGU CUGAUGAG GCCGUUAGGC CGAA ICAUCAGC
3221





2307
GAUGCUAC U AAGGAUGA
1033
UCAUCCUU CUGAUGAG GCCGUUAGGC CGAA IUAGCAUC
3222





2323
ACGGUGUC U ACUCAAGG
1034
CCUUGAGU CUGAUGAG GCCGUUAGGC CGAA IACACCGU
3223





2326
GUGUCUAC U CAAGGUAU
1035
AUACCUUG CUGAUGAG GCCGUUAGGC CGAA IUAGACAC
3224





2328
GUCUACUC A AGGUAUUU
1036
AAAUACCU CUGAUGAG GCCGUUAGGC CGAA IAGUAGAC
3225





2338
GGUAUUUC A CAACUUAU
1037
AUAAGUUG CUGAUGAG GCCGUUAGGC CGAA IAAAUACC
3226





2340
UAUUUCAC A ACUUAUGA
1038
UCAUAAGU CUGAUGAG GCCGUUAGGC CGAA IUGAAAUA
3227





2343
UUCACAAC U UAUGACAC
1039
GUGUCAUA CUGAUGAG GCCGUUAGGC CGAA IUUGUGAA
3228





2350
CUUAUGAC A CGAAUGGU
1040
ACCAUUCG CUGAUGAG GCCGUUAGGC CGAA IUCAUAAG
3229





2365
GUAGAUAC A GUGUAAAA
1041
UUUUACAC CUGAUGAG GCCGUUAGGC CGAA IUAUCUAC
3230





2382
GUGCGGGC U CUGGGAGG
1042
CCUCCCAG CUGAUGAG GCCGUUAGGC CGAA ICCCGCAC
3231





2384
GCGGGCUC U GGGAGGAG
1043
CUCCUCCC CUGAUGAG GCCGUUAGGC CGAA IAGCCCGC
3232





2400
GUUAACGC A GCCAGACG
1044
CGUCUGGC CUGAUGAG GCCGUUAGGC CGAA ICGUUAAC
3233





2403
AACGCAGC C AGACGGAG
1045
CUCCGUCU CUGAUGAG GCCGUUAGGC CGAA ICUGCGUU
3234





2404
ACGCAGCC A GACGGAGA
1046
UCUCCGUC CUGAUGAG GCCGUUAGGC CGAA IGCUGCGU
3235





2420
AGUGAUAC C CCAGCAGA
1047
UCUGCUGG CUGAUGAG GCCGUUAGGC CGAA IUAUCACU
3236





2421
GUGAUACC C CAGCAGAG
1048
CUCUGCUG CUGAUGAG GCCGUUAGGC CGAA IGUAUCAC
3237





2422
UGAUACCC C AGCAGAGU
1049
ACUCUGCU CUGAUGAG GCCGUUAGGC CGAA IGGUAUCA
3238





2423
GAUACCCC A GCAGAGUG
1050
CACUCUGC CUGAUGAG GCCGUUAGGC CGAA IGGGUAUC
3239





2426
ACCCCAGC A GAGUGGAG
1051
CUCCACUC CUGAUGAG GCCGUUAGGC CGAA ICUGGGGU
3240





2436
AGUGGAGC A CUGUACAU
1052
AUGUACAG CUGAUGAG GCCGUUAGGC CGAA ICUCCACU
3241





2438
UGGAGCAC U GUACAUAC
1053
GUAUGUAC CUGAUGAG GCCGUUAGGC CGAA IUGCUCCA
3242





2443
CACUGUAC A UACCUGGC
1054
GCCAGGUA CUGAUGAG GCCGUUAGGC CGAA IUACAGUG
3243





2447
GUACAUAC C UGGCUGGA
1055
UCCAGCCA CUGAUGAG GCCGUUAGGC CGAA IUAUGUAC
3244





2448
UACAUACC U GGCUGGAU
1056
AUCCAGCC CUGAUGAG GCCGUUAGGC CGAA IGUAUGUA
3245





2452
UACCUGGC U GGAUUGAG
1057
CUCAAUCC CUGAUGAG GCCGUUAGGC CGAA ICCAGGUA
3246





2474
UGAAAUAC A AUGGAAUC
1058
GAUUCCAU CUGAUGAG GCCGUUAGGC CGAA IUAUUUCA
3247





2483
AUGGAAUC C ACCAAGAC
1059
GUCUUGGU CUGAUGAG GCCGUUAGGC CGAA IAUUCCAU
3248





2484
UGGAAUCC A CCAAGACC
1060
GGUCUUGG CUGAUGAG GCCGUUAGGC CGAA IGAUUCCA
3249





2486
GAAUCCAC C AAGACCUG
1061
CAGGUCUU CUGAUGAG GCCGUUAGGC CGAA IUGGAUUC
3250





2487
AAUCCACC A AGACCUGA
1062
UCAGGUCU CUGAUGAG GCCGUUAGGC CGAA IGUGGAUU
3251





2492
ACCAAGAC C UGAAAUUA
1063
UAAUUUCA CUGAUGAG GCCGUUAGGC CGAA IUCUUGGU
3252





2493
CCAAGACC U GAAAUUAA
1064
UUAAUUUC CUGAUGAG GCCGUUAGGC CGAA IGUCUUGG
3253





2516
UGAUGUUC A ACACAAGC
1065
GCUUGUGU CUGAUGAG GCCGUUAGGC CGAA IAACAUCA
3254





2519
UGUUCAAC A CAAGCAAG
1066
CUUGCUUG CUGAUGAG GCCGUUAGGC CGAA IUUGAACA
3255





2521
UUCAACAC A AGCAAGUG
1067
CACUUGCU CUGAUGAG GCCGUUAGGC CGAA IUGUUGAA
3256





2525
ACACAAGC A AGUGUGUU
1068
AACACACU CUGAUGAG GCCGUUAGGC CGAA ICUUGUGU
3257





2536
UGUGUUUC A GCAGAACA
1069
UGUUCUGC CUGAUGAG GCCGUUAGGC CGAA IAAACACA
3258





2539
GUUUCAGC A GAACAUCC
1070
GGAUGUUC CUGAUGAG GCCGUUAGGC CGAA ICUGAAAC
3259





2544
AGCAGAAC A UCCUCGGG
1071
CCCGAGGA CUGAUGAG GCCGUUAGGC CGAA IUUCUGCU
3260





2547
AGAACAUC C UCGGGAGG
1072
CCUCCCGA CUGAUGAG GCCGUUAGGC CGAA IAUGUUCU
3261





2548
GAACAUCC U CGGGAGGC
1073
GCCUCCCG CUGAUGAG GCCGUUAGGC CGAA IGAUGUUC
3262





2557
CGGGAGGC U CAUUUGUG
1074
CACAAAUG CUGAUGAG GCCGUUAGGC CGAA ICCUCCCG
3263





2559
GGAGGCUC A UUUGUGGC
1075
GCCACAAA CUGAUGAG GCCGUUAGGC CGAA IAGCCUCC
3264





2568
UUUGUGGC U UCUGAUGU
1076
ACAUCAGA CUGAUGAG GCCGUUAGGC CGAA ICCACAAA
3265





2571
GUGGCUUC U GAUGUCCC
1077
GGGACAUC CUGAUGAG GCCGUUAGGC CGAA IAAGCCAC
3266





2578
CUGAUGUC C CAAAUGCU
1078
AGCAUUUG CUGAUGAG GCCGUUAGGC CGAA IACAUCAG
3267





2579
UGAUGUCC C AAAUGCUC
1079
GAGCAUUU CUGAUGAG GCCGUUAGGC CGAA IGACAUCA
3268





2580
GAUGUCCC A AAUGCUCC
1080
GGAGCAUU CUGAUGAG GCCGUUAGGC CGAA IGGACAUC
3269





2586
CCAAAUGC U CCCAUACC
1081
GGUAUGGG CUGAUGAG GCCGUUAGGC CGAA ICAUUUGG
3270





2588
AAAUGCUC C CAUACCUG
1082
CAGGUAUG CUGAUGAG GCCGUUAGGC CGAA IAGCAUUU
3271





2589
AAUGCUCC C AUACCUGA
1083
UCAGGUAU CUGAUGAG GCCGUUAGGC CGAA IGAGCAUU
3272





2590
AUGCUCCC A UACCUGAU
1084
AUCAGGUA CUGAUGAG GCCGUUAGGC CGAA IGGAGCAU
3273





2594
UCCCAUAC C UGAUCUCU
1085
AGAGAUCA CUGAUGAG GCCGUUAGGC CGAA IUAUGGGA
3274





2595
CCCAUACC U GAUCUCUU
1086
AAGAGAUC CUGAUGAG GCCGUUAGGC CGAA IGUAUGGG
3275





2600
ACCUGAUC U CUUCCCAC
1087
GUGGGAAG CUGAUGAG GCCGUUAGGC CGAA IAUCAGGU
3276





2602
CUGAUCUC U UCCCACCU
1088
AGGUGGGA CUGAUGAG GCCGUUAGGC CGAA IAGAUCAG
3277





2605
AUCUCUUC C CACCUGGC
1089
GCCAGGUG CUGAUGAG GCCGUUAGGC CGAA IAAGAGAU
3278





2606
UCUCUUCC C ACCUGGCC
1090
GGCCAGGU CUGAUGAG GCCGUUAGGC CGAA IGAAGAGA
3279





2607
CUCUUCCC A CCUGGCCA
1091
UGGCCAGG CUGAUGAG GCCGUUAGGC CGAA IGGAAGAG
3280





2609
CUUCCCAC C UGGCCAAA
1092
UUUGGCCA CUGAUGAG GCCGUUAGGC CGAA IUGGGAAG
3281





2610
UUCCCACC U GGCCAAAU
1093
AUUUGGCC CUGAUGAG GCCGUUAGGC CGAA IGUGGGAA
3282





2614
CACCUGGC C AAAUCACC
1094
GGUGAUUU CUGAUGAG GCCGUUAGGC CGAA ICCAGGUG
3283





2615
ACCUGGCC A AAUCACCG
1095
CGGUGAUU CUGAUGAG GCCGUUAGGC CGAA IGCCAGGU
3284





2620
GCCAAAUC A CCGACCUG
1096
CAGGUCGG CUGAUGAG GCCGUUAGGC CGAA IAUUUGGC
3285





2622
CAAAUCAC C GACCUGAA
1097
UUCAGGUC CUGAUGAG GCCGUUAGGC CGAA IUGAUUUG
3286





2626
UCACCGAC C UGAAGGCG
1098
CGCCUUCA CUGAUGAG GCCGUUAGGC CGAA IUCGGUGA
3287





2627
CACCGACC U GAAGGCGG
1099
CCGCCUUC CUGAUGAG GCCGUUAGGC CGAA IGUCGGUG
3288





2642
GGAAAUUC A CGGGGGCA
1100
UGCCCCCG CUGAUGAG GCCGUUAGGC CGAA IAAUUUCC
3289





2650
ACGGGGGC A GUCUCAUU
1101
AAUGAGAC CUGAUGAG GCCGUUAGGC CGAA ICCCCCGU
3290





2654
GGGCAGUC U CAUUAAUC
1102
GAUUAAUG CUGAUGAG GCCGUUAGGC CGAA IACUGCCC
3291





2656
GCAGUCUC A UUAAUCUG
1103
CAGAUUAA CUGAUGAG GCCGUUAGGC CGAA IAGACUGC
3292





2663
CAUUAAUC U GACUUGGA
1104
UCCAAGUC CUGAUGAG GCCGUUAGGC CGAA IAUUAAUG
3293





2667
AAUCUGAC U UGGACAGC
1105
GCUGUCCA CUGAUGAG GCCGUUAGGC CGAA IUCAGAUU
3294





2673
ACUUGGAC A GCUCCUGG
1106
CCAGGAGC CUGAUGAG GCCGUUAGGC CGAA IUCCAAGU
3295





2676
UGGACAGC U CCUGGGGA
1107
UCCCCAGG CUGAUGAG GCCGUUAGGC CGAA ICUGUCCA
3296





2678
GACAGCUC C UGGGGAUG
1108
CAUCCCCA CUGAUGAG GCCGUUAGGC CGAA IAGCUGUC
3297





2679
ACAGCUCC U GGGGAUGA
1109
UCAUCCCC CUGAUGAG GCCGUUAGGC CGAA IGAGCUGU
3298





2695
AUUAUGAC C AUGGAACA
1110
UGUUCCAU CUGAUGAG GCCGUUAGGC CGAA IUCAUAAU
3299





2696
UUAUGACC A UGGAACAG
1111
CUGUUCCA CUGAUGAG GCCGUUAGGC CGAA IGUCAUAZ
3300





2703
CAUGGAAC A GCUCACAA
1112
UUGUGAGC CUGAUGAG GCCGUUAGGC CGAA IUUCCAUG
3301





2706
GGAACAGC U CACAAGUA
1113
UACUUGUG CUGAUGAG GCCGUUAGGC CGAA ICUGUUCC
3302





2708
AACAGCUC A CAAGUAUA
1114
UAUACUUG CUGAUGAG GCCGUUAGGC CGAA IAGCUGUU
3303





2710
CAGCUCAC A AGUAUAUC
1115
GAUAUACU CUGAUGAG GCCGUUAGGC CGAA IUGAGCUG
3304





2719
AGUAUAUC A UUCGAAUA
1116
UAUUCGAA CUGAUGAG GCCGUUAGGC CGAA IAUAUACU
3305





2733
AUAAGUAC A AGUAUUCU
1117
AGAAUACU CUGAUGAG GCCGUUAGGC CGAA IUACUUAU
3306





2741
AAGUAUUC U UGAUCUCA
1118
UGAGAUCA CUGAUGAG GCCGUUAGGC CGAA IAAUACUU
3307





2747
UCUUGAUC U CAGAGACA
1119
UGUCUCUG CUGAUGAG GCCGUUAGGC CGAA IAUCAAGA
3308





2749
UUGAUCUC A GAGACAAG
1120
CUUGUCUC CUGAUGAG GCCGUUAGGC CGAA IAGAUCAA
3309





2755
UCAGAGAC A AGUUCAAU
1121
AUUGAACU CUGAUGAG GCCGUUAGGC CGAA IUCUCUGA
3310





2761
ACAAGUUC A AUGAAUCU
1122
AGAUUCAU CUGAUGAG GCCGUUAGGC CGAA IAACUUGU
3311





2769
AAUGAAUC U CUUCAAGU
1123
ACUUGAAG CUGAUGAG GCCGUUAGGC CGAA IAUUCAUU
3312





2771
UGAAUCUC U UCAAGUGA
1124
UCACUUGA CUGAUGAG GCCGUUAGGC CGAA IAGAUUCA
3313





2774
AUCUCUUC A AGUGAAUA
1125
UAUUCACU CUGAUGAG GCCGUUAGGC CGAA IAAGAGAU
3314





2784
GUGAAUAC U ACUGCUCU
1126
AGAGCAGU CUGAUGAG GCCGUUAGGC CGAA IUAUUCAC
3315





2787
AAUACUAC U GCUCUCAU
1127
AUGAGAGC CUGAUGAG GCCGUUAGGC CGAA IUAGUAUU
3316





2790
ACUACUGC U CUCAUCCC
1128
GGGAUGAG CUGAUGAG GCCGUUAGGC CGAA ICAGUAGU
3317





2792
UACUGCUC U CAUCCCAA
1129
UUGGGAUG CUGAUGAG GCCGUUAGGC CGAA IAGCAGUA
3318





2794
CUGCUCUC A UCCCAAAG
1130
CUUUGGGA CUGAUGAG GCCGUUAGGC CGAA IAGAGCAG
3319





2797
CUCUCAUC C CAAAGGAA
1131
UUCCUUUG CUGAUGAG GCCGUUAGGC CGAA IAUGAGAG
3320





2798
UCUCAUCC C AAAGGAAG
1132
CUUCCUUU CUGAUGAG GCCGUUAGGC CGAA IGAUGAGA
3321





2799
CUCAUCCC A AAGGAAGC
1133
GCUUCCUU CUGAUGAG GCCGUUAGGC CGAA IGGAUGAG
3322





2808
AAGGAAGC C AACUCUGA
1134
UCAGAGUU CUGAUGAG GCCGUUAGGC CGAA ICUUCCUU
3323





2809
AGGAAGCC A ACUCUGAG
1135
CUCAGAGU CUGAUGAG GCCGUUAGGC CGAA IGCUUCCU
3324





2812
AAGCCAAC U CUGAGGAA
1136
UUCCUCAG CUGAUGAG GCCGUUAGGC CGAA IUUGGCUU
3325





2814
GCCAACUC U GAGGAAGU
1137
ACUUCCUC CUGAUGAG GCCGUUAGGC CGAA IAGUUGGC
3326





2824
AGGAAGUC U UUUUGUUU
1138
AAACAAAA CUGAUGAG GCCGUUAGGC CGAA IACUUCCU
3327





2837
GUUUAAAC C AGAAAACA
1139
UGUUUUCU CUGAUGAG GCCGUUAGGC CGAA IUUUAAAC
3328





2838
UUUAAACC A GAAAACAU
1140
AUGUUUUC CUGAUGAG GCCGUUAGGC CGAA IGUUUAAA
3329





2845
CAGAAAAC A UUACUUUU
1141
AAAAGUAA CUGAUGAG GCCGUUAGGC CGAA IUUUUCUG
3330





2850
AACAUUAC U UUUGAAAA
1142
UUUUCAAA CUGAUGAG GCCGUUAGGC CGAA IUAAUGUU
3331





2863
AAAAUGGC A CAGAUCUU
1143
AAGAUCUG CUGAUGAG GCCGUUAGGC CGAA ICCAUUUU
3332





2865
AAUGGCAC A GAUCUUUU
1144
AAAAGAUC CUGAUGAG GCCGUUAGGC CGAA IUGCCAUU
3333





2870
CACAGAUC U UUUCAUUG
1145
CAAUGAAA CUGAUGAG GCCGUUAGGC CGAA IAUCUGUG
3334





2875
AUCUUUUC A UUGCUAUU
1146
AAUAGCAA CUGAUGAG GCCGUUAGGC CGAA IAAAAGAU
3335





2880
UUCAUUGC U AUUCAGGC
1147
GCCUGAZU CUGAUGAG GCCGUUAGGC CGAA ICAAUGAA
3336





2885
UGCUAUUC A GGCUGUUG
1148
CAACAGCC CUGAUGAG GCCGUUAGGC CGAA IAAUAGCA
3337





2889
AUUCAGGC U GUUGAUAA
1149
UUAUCAAC CUGAUGAG GCCGUUAGGC CGAA ICCUGAAU
3338





2906
GGUCGAUC U GAAAUCAG
1150
CUGAUUUC CUGAUGAG GCCGUUAGGC CGAA IAUCGACC
3339





2913
CUGAAAUC A GAAAUAUC
1151
GAUAUUUC CUGAUGAG GCCGUUAGGC CGAA IAUUUCAG
3340





2922
GAAAUAUC C AACAUUGC
1152
GCAAUGUU CUGAUGAG GCCGUUAGGC CGAA IAUAUUUC
3341





2923
AAAUAUCC A ACAUUGCA
1153
UGCAAUGU CUGAUGAG GCCGUUAGGC CGAA IGAUAUUU
3342





2926
UAUCCAAC A UUGCACGA
1154
UCGUGCAA CUGAUGAG GCCGUUAGGC CGAA IUUGGAUA
3343





2931
AACAUUGC A CGAGUAUC
1155
GAUACUCG CUGAUGAG GCCGUUAGGC CGAA ICAAUGUU
3344





2940
CGAGUAUC U UUGUUUAU
1156
AUAAACAA CUGAUGAG GCCGUUAGGC CGAA IAUACUCG
3345





2951
GUUUAUUC C UCCACAGA
1157
UCUGUGGA CUGAUGAG GCCGUUAGGC CGAA IAAUAAAC
3346





2952
UUUAUUCC U CCACAGAC
1158
GUCUGUGG CUGAUGAG GCCGUUAGGC CGAA IGAAUAAA
3347





2954
UAUUCCUC C ACAGACUC
1159
GAGUCUGU CUGAUGAG GCCGUUAGGC CGAA IAGGAAUA
3348





2955
AUUCCUCC A CAGACUCC
1160
OGAGUCUG CUGAUGAG GCCGUUAGGC CGAA IGAGGAAU
3349





2957
UCCUCCAC A GACUCCGC
1161
GCGGAGUC CUGAUGAG GCCGUUAGGC CGAA IUGGAGGA
3350





2961
CCACAGAC U CCGCCAGA
1162
UCUGGCGG CUGAUGAG GCCGUUAGGC CGAA IUCUGUGG
3351





2963
ACAGACUC C GCCAGAGA
1163
UCUCUGGC CUGAUGAG GCCGUUAGGC CGAA IAGUCUGU
3352





2966
GACUCCGC C AGAGACAC
1164
GUGUCUCU CUGAUGAG GCCGUUAGGC CGAA ICGGAGUC
3353





2967
ACUCCGCC A GAGACACC
1165
GGUGUCUC CUGAUGAG GCCGUUAGGC CGAA IGCGGAGU
3354





2973
CCAGAGAC A CCUAGUCC
1166
GGACUAGG CUGAUGAG GCCGUUAGGC CGAA IUCUCUGG
3355





2975
AGAGACAC C UAGUCCUG
1167
CAGGACUA CUGAUGAG GCCGUUAGGC CGAA IUGUCUCU
3356





2976
GAGACACC U AGUCCUGA
1168
UCAGGACU CUGAUGAG GCCGUUAGGC CGAA IGUGUCUC
3357





2981
ACCUAGUC C UGAUGAAA
1169
UUUCAUCA CUGAUGAG GCCGUUAGGC CGAA IACUAGGU
3358





2982
CCUAGUCC U GAUGAAAC
1170
GUUUCAUC CUGAUGAG GCCGUUAGGC CGAA IGACUAGG
3359





2994
GAAACGUC U GCUCCUUG
1171
CAAGGAGC CUGAUGAG GCCGUUAGGC CGAA IACGUUUC
3360





2997
ACGUCUGC U CCUUGUCC
1172
GGACAAGG CUGAUGAG GCCGUUAGGC CGAA ICAGACGU
3361





2999
GUCUGCUC C UUGUCCUA
1173
UAGGACAA CUGAUGAG GCCGUUAGGC CGAA IAGCAGAC
3362





3000
UCUGCUCC U UGUCCUAA
1174
UUAGGACA CUGAUGAG GCCGUUAGGC CGAA IGAGCAGA
3363





3005
UCCUUGUC C UAAUAUUC
1175
GAAUAUUA CUGAUGAG GCCGUUAGGC CGAA IACAAGGA
3364





3006
CCUUGUCC U AAUAUUCA
1176
UGAAUAUU CUGAUGAG GCCGUUAGGC CGAA IGACAAGG
3365





3014
UAAUAUUC A UAUCAACA
1177
UGUUGAUA CUGAUGAG GCCGUUAGGC CGAA IAAUAUUA
3366





3019
UUCAUAUC A ACAGCACC
1178
GGUGCUGU CUGAUGAG GCCGUUAGGC CGAA IAUAUGAA
3367





3022
AUAUCAAC A GCACCAUU
1179
AAUGGUGC CUGAUGAG GCCGUUAGGC CGAA IUUGAUAU
3368





3025
UCAACAGC A CCAUUCCU
1180
AGGAAUGG CUGAUGAG GCCGUUAGGC CGAA ICUGUUGA
3369





3027
AACAGCAC C AUUCCUGG
1181
CCAGGAAU CUGAUGAG GCCGUUAGGC CGAA IUGCUGUU
3370





3028
ACAGCACC A UUCCUGGC
1182
GCCAGGAA CUGAUGAG GCCGUUAGGC CGAA IGUGCUGU
3371





3032
CACCAUUC C UGGCAUUC
1183
GAAUGCCA CUGAUGAG GCCGUUAGGC CGAA IAAUGGUG
3372





3033
ACCAUUCC U GGCAUUCA
1184
UGAAUGCC CUGAUGAG GCCGUUAGGC CGAA IGAAUGGU
3373





3037
UUCCUGGC A UUCACAUU
1185
AAUGUGAA CUGAUGAG GCCGUUAGGC CGAA ICCAGGAA
3374





3041
UGGCAUUC A CAUUUUAA
1186
UUAAAAUG CUGAUGAG GCCGUUAGGC CGAA IAAUGCCA
3375





3043
GCAUUCAC A UUUUAAAA
1187
UUUUAAAA CUGAUGAG GCCGUUAGGC CGAA IUGAAUGC
3376





3077
AGGAGAAC U GCAGCUGU
1188
ACAGCUGC CUGAUGAG GCCGUUAGGC CGAA IUUCUCCU
3377





3080
AGAACUGC A GCUGUCAA
1189
UUGACAGC CUGAUGAG GCCGUUAGGC CGAA ICAGUUCU
3378





3083
ACUGCAGC U GUCAAUAG
1190
CUAUUGAC CUGAUGAG GCCGUUAGGC CGAA ICUGCAGU
3379





3087
CAGCUGUC A AUAGCCUA
1191
UAGGCUAU CUGAUGAG GCCGUUAGGC CGAA IACAGCUG
3380





3093
UCAAUAGC C UAGGGCUG
1192
CAGCCCUA CUGAUGAG GCCGUUAGGC CGAA ICUAUUGA
3381





3094
CAAUAGCC U AGGGCUGA
1193
UCAGCCCU CUGAUGAG GCCGUUAGGC CGAA IGCUAUUG
3382





3100
CCUAGGGC U GAAUUUUU
1194
AAAAAUUC CUGAUGAG GCCGUUAGGC CGAA ICCCUAGG
3383





3112
UUUUUGUC A GAUAAAUA
1195
UAUUUAUC CUGAUGAG GCCGUUAGGC CGAA IACAAAAA
3384





3130
AAUAAAUC A UUCAUCCU
1196
AGGAUGAA CUGAUGAG GCCGUUAGGC CGAA IAUUUAUU
3385





3134
AAUCAUUC A UCCUUUUU
1197
AAAAAGGA CUGAUGAG GCCGUUAGGC CGAA IAAUGAUU
3386





3137
CAUUCAUC C UUUUUUUG
1198
CAAAAAAA CUGAUGAG GCCGUUAGGC CGAA IAUGAAUG
3387





3138
AUUCAUCC U UUUUUUGA
1199
UCAAAAAA CUGAUGAG GCCGUUAGGC CGAA IGAUGAAU
3388





3160
AAAUUUUC U AAAAUGUA
1200
UACAUUUU CUGAUGAG GCCGUUAGGC CGAA IAAAAUUU
3389





3177
UUUUAGAC U UCCUGUAG
1201
CUACAGGA CUGAUGAG GCCGUUAGGC CGAA IUCUAAAA
3390





3267
UUUUAGAC U UCCUGUAG
1201
CUACAGGA CUGAUGAG GCCGUUAGGC CGAA IUCUAAAA
3390





3180
UAGACUUC C UGUAGGGG
1202
CCCCUACA CUGAUGAG GCCGUUAGGC CGAA IAAGUCUA
3391





3270
UAGACUUC C UGUAGGGG
1202
CCCCUACA CUGAUGAG GCCGUUAGGC CGAA IAAGUCUA
3391





3181
AGACUUCC U GUAGGGGG
1203
CCCCCUAC CUGAUGAG GCCGUUAGGC CGAA IGAAGUCU
3392





3271
AGACUUCC U GUAGGGGG
1203
CCCCCUAC CUGAUGAG GCCGUUAGGC CGAA IGAAGUCU
3392





3198
CGAUAUAC U AAAUGUAU
1204
AUACAUUU CUGAUGAG GCCGUUAGGC CGAA IUAUAUCG
3393





3251
CGAUAUAC U AAAUGUAU
1204
AUACAUUU CUGAUGAG GCCGUUAGGC CGAA IUAUAUCG
3393





3214
UAUAGUAC A UUUAUACU
1205
AGUAUAAA CUGAUGAG GCCGUUAGGC CGAA IUACUAUA
3394





3222
AUUUAUAC U AAAUGUAU
1206
AUACAUUU CUGAUGAG GCCGUUAGGC CGAA IUAUAAAU
3395





3233
AUGUAUUC C UGUAGGGG
1207
CCCCUACA CUGAUGAG GCCGUUAGGC CGAA IAAUACAU
3396





3234
UGUAUUCC U GUAGGGGG
1208
CCCCCUAC CUGAUGAG GCCGUUAGGC CGAA IGAAUACA
3397





3296
UAAAAUGC U AAACAACU
1209
AGUUGUUU CUGAUGAG GCCGUUAGGC CGAA ICAUUUUA
3398





3301
UGCUAAAC A ACUGGGUA
1210
UACCCAGU CUGAUGAG GCCGUUAGGC CGAA IUUUAGCA
3399






Input Sequence = NM_001285. Cut Site = CH/.




Arm Length = 8. Core Sequence = CUGAUGAG GCCGUUAGGC CGAA




Underlined region can be any X sequence or linker, as described herein.




NM_001285 (Homo sapiens chloride channel, calcium activated, 1 (CLCA1) mRNA, 3311 bp)








[0192]

5





TABLE V










Human CLCA1 G-cleaver Ribozyme and Target Sequence













Seq ID

Rz Seq


Pos
Substrate
No.
Ribozyme
ID No.














40
AUAUAAUU G AAUAUUUU
1211
AAAAUAUU UGAUG GCAUGCACUAUGC GCG AAUUAUAU
3400





67
GGGAGCAU G AAGAGGUG
1212
CACCUCUU UGAUG GCAUGCACUAUGC GCG AUGCUCCC
3401





78
GAGGUGUU G AGGUUAUG
1213
CAUAACCU UGAUG GCAUGCACUAUGC GCG AACACCUC
3402





106
GCACAGCU G AAGGCAGA
1214
UCUGCCUU UGAUG GCAUGCACUAUGC GCG AGCUGUGC
3403





134
ACAAGUAC G CAAUUUGA
1215
UCAAAUUG UGAUG GCAUGCACUAUGC GCG GUACUUGU
3404





141
CGCAAUUU G AGACUAAG
1216
CUUAGUCU UGAUG GCAUGCACUAUGC GCG AAAUUGCG
3405





172
CUCCUAUU G AAGACAAG
1217
CUUGUCUU UGAUG GCAUGCACUAUGC GCG AAUAGGAG
3406





223
AGACCUGU G AUAAACCA
1218
UGGUUUAU UGAUG GCAUGCACUAUGC GCG ACAGGUCU
3407





237
CCACUUCC G AUAAGUUG
1219
CAACUUAU UGAUG GCAUGCACUAUGC GCG GGAAGUGG
3408





312
CGUAACCC G CAUUUUCC
1220
GGAAAAUG UGAUG GCAUGCACUAUGC GCG GGGUUACG
3409





384
UUCAUCUU G AUUCUUCA
1221
UGAAGAAU UGAUG GCAUGCACUAUGC GCG AAGAUGAA
3410





411
GGGGCCCU G AGUAAUUC
1222
GAAUUACU UGAUG GCAUGCACUAUGC GCG AGGGCCCC
3411





432
AUUCAGCU G AACAACAA
1223
UUGUUGUU UGAUG GCAUGCACUAUGC GCG AGCUGAAU
3412





448
AUGGCUAU G AAGGCAUU
1224
AAUGCCUU UGAUG GCAUGCACUAUGC GCG AUAGCCAU
3413





463
UUGUCGUU G CAAUCGAC
1225
GUCGAUUG UGAUG GCAUGCACUAUGC GCG AACGACAA
3414





469
UUGCAAUC G ACCCCAAU
1226
AUUGGGGU UGAUG GCAUGCACUAUGC GCG GAUUGCAA
3415





480
CCCAAUGU G CCAGAAGA
1227
UCUUCUGG UGAUG GCAUGCACUAUGC GCG ACAUUGGG
3416





490
CAGAAGAU G AAACACUC
1228
GAGUGUUU UGAUG GCAUGCACUAUGC GCG AUCUUCUG
3417





522
GACAUGGU G ACCCAGGC
1229
GCCUGGGU UGAUG GCAUGCACUAUGC GCG ACCAUGUC
3418





547
AUCUGUUU G AAGCUACA
1230
UGUAGCUU UGAUG GCAUGCACUAUGC GCG AAACAGAU
3419





563
AGGAAAGC G AUUUUAUU
1231
AAUAAAAU UGAUG GCAUGCACUAUGC GCG GCUUUCCU
3420





583
AAAAUGUU G CCAUUUUG
1232
CAAAAUGG UGAUG GCAUGCACUAUGC GCG AACAUUUU
3421





591
GCCAUUUU G AUUCCUGA
1233
UCAGGAAU UGAUG GCAUGCACUAUGC GCG AAAAUGGC
3422





598
UGAUUCCU G AAACAUGG
1234
CCAUGUUU UGAUG GCAUGCACUAUGC GCG AGGAAUCA
3423





619
CAAAGGCU G ACUAUGUG
1235
CACAUAGU UGAUG GCAUGCACUAUGC GCG AGCCUUUG
3424





627
GACUAUGU G AGACCAAA
1236
UUUGGUCU UGAUG GCAUGCACUAUGC GCG ACAUAGUC
3425





640
CAAAACUU G AGACCUAC
1237
GUAGGUCU UGAUG GCAUGCACUAUGC GCG AAGUUUUG
3426





655
ACAAAAAU G CUGAUGUU
1238
AACAUCAG UGAUG GCAUGCACUAUGC GCG AUUUUUGU
3427





658
AAAAUGCU G AUGUUCUG
1239
CAGAACAU UGAUG GCAUGCACUAUGC GCG AGCAUUUU
3428





670
UUCUGGUU G CUGAGUCU
1240
AGACUCAG UGAUG GCAUGCACUAUGC GCG AACCAGAA
3429





673
UGGUUGCU G AGUCUACU
1241
AGUAGACU UGAUG GCAUGCACUAUGC GCG AGCAACCA
3430





694
CAGGUAAU G AUGAACCC
1242
GGGUUCAU UGAUG GCAUGCACUAUGC GCG AUUACCUG
3431





697
GUAAUGAU G AACCCUAC
1243
GUAGGGUU UGAUG GCAUGCACUAUGC GCG AUCAUUAC
3432





709
CCUACACU G AGCAGAUG
1244
CAUCUGCU UGAUG GCAUGCACUAUGC GCG AGUGUAGG
3433





739
AGAAGGGU G AAAGGAUC
1245
GAUCCUUU UGAUG GCAUGCACUAUGC GCG ACCCUUCU
3434





760
UCACUCCU G AUUUCAUU
1246
AAUGAAAU UGAUG GCAUGCACUAUGC GCG AGGAGUGA
3435





769
AUUUCAUU G CAGGAAAA
1247
UUUUCCUG UGAUG GCAUGCACUAUGC GCG AAUGAAAU
3436





787
AGUUAGCU G AAUAUGGA
1248
UCCAUAUU UGAUG GCAUGCACUAUGC GCG AGCUAACU
3437





820
UUGUCCAU G AGUGGGCU
1249
AGCCCACU UGAUG GCAUGCACUAUGC GCG AUGGACAA
3438





836
UCAUCUAC G AUGGGGAG
1250
CUCCCCAU UGAUG GCAUGCACUAUGC GCG GUAGAUGA
3439





850
GAGUAUUU G ACGAGUAC
1251
GUACUCGU UGAUG GCAUGCACUAUGC GCG AAAUACUC
3440





853
UAUUUGAC G AGUACAAU
1252
AUUGUACU UGAUG GCAUGCACUAUGC GCG GUCAAAUA
3441





865
ACAAUAAU G AUGAGAAA
1253
UUUCUCAU UGAUG GCAUGCACUAUGC GCG AUUAUUGU
3442





868
AUAAUGAU G AGAAAUUC
1254
GAAUUUCU UGAUG GCAUGCACUAUGC GCG AUCAUUAU
3443





980
CAAAAGAU G CACAUUCA
1255
UGAAUGUG UGAUG GCAUGCACUAUGC GCG AUCUUUUG
3444





1009
GACUCUAU G AAAAAGGA
1256
UCCUUUUU UGAUG GCAUGCACUAUGC GCG AUAGAGUC
3445





1021
AAGGAUGU G AGUUUGUU
1257
AACAAACU UGAUG GCAUGCACUAUGC GCG ACAUCCUU
3446





1040
CCAAUCCC G CCAGACGG
1258
CCGUCUGG UGAUG GCAUGCACUAUGC GCG GGGAUUGG
3447





1069
UAAUGUUU G CACAACAU
1259
AUGUUGUG UGAUG GCAUGCACUAUGC GCG AAACAUUA
3448





1081
AACAUGUU G AUUCUAUA
1260
UAUAGAAU UGAUG GCAUGCACUAUGC GCG AACAUGUU
3449





1093
CUAUAGUU G AAUUCUGU
1261
ACAGAAUU UGAUG GCAUGCACUAUGC GCG AACUAUAG
3450





1151
UCAAAAAU G CAAUCUCC
1262
GGAGAUUG UGAUG GCAUGCACUAUGC GCG AUUUUUGA
3451





1160
CAAUCUCC G AAGCACAU
1263
AUGUGCUU UGAUG GCAUGCACUAUGC GCG GGAGAUUG
3452





1176
UGGGAAGU G AUCCGUGA
1264
UCACGGAU UGAUG GCAUGCACUAUGC GCG ACUUCCCA
3453





1183
UGAUCCGU G AUUCUGAG
1265
CUCAGAAU UGAUG GCAUGCACUAUGC GCG ACGGAUCA
3454





1189
GUGAUUCU G AGGACUUU
1266
AAAGUCCU UGAUG GCAUGCACUAUGC GCG AGAAUCAC
3455





1215
ACUCCUAU G ACAACACA
1267
UGUGUUGU UGAUG GCAUGCACUAUGC GCG AUAGGAGU
3456





1248
UUCUCAUU G CUGCAGAU
1268
AUCUGCAG UGAUG GCAUGCACUAUGC GCG AAUGAGAA
3457





1251
UCAUUGCU G CAGAUUGG
1269
CCAAUCUG UGAUG GCAUGCACUAUGC GCG AGCAAUGA
3458





1285
UAGUCCUU G ACAAAUCU
1270
AGAUUUGU UGAUG GCAUGCACUAUGC GCG AAGGACUA
3459





1305
AGCAUGGC G ACUGGUAA
1271
UUACCAGU UGAUG GCAUGCACUAUGC GCG GCCAUGCU
3460





1316
UGGUAACC G CCUCAAUC
1272
GAUUGAGG UGAUG GCAUGCACUAUGC GCG GGUUACCA
3461





1325
CCUCAAUC G ACUGAAUC
1273
GAUUCAGU UGAUG GCAUGCACUAUGC GCG GAUUGAGG
3462





1329
AAUCGACU G AAUCAAGC
1274
GCUUGAUU UGAUG GCAUGCACUAUGC GCG AGUCGAUU
3463





1353
CUUUUCCU G CUGCAGAC
1275
GUCUGCAG UGAUG GCAUGCACUAUGC GCG AGGAAAAG
3464





1356
UUCCUGCU G CAGACAGU
1276
ACUGUCUG UGAUG GCAUGCACUAUGC GCG AGCAGGAA
3465





1366
AGACAGUU G AGCUGGGG
1277
CCCCAGCU UGAUG GCAUGCACUAUGC GCG AACUGUCU
3466





1392
GGGAUGGU G ACAUUUGA
1278
UCAAAUGU UGAUG GCAUGCACUAUGC GCG ACCAUCCC
3467





1399
UGACAUUU G ACAGUGCU
1279
AGCACUGU UGAUG GCAUGCACUAUGC GCG AAAUGUCA
3468





1405
UUGACAGU G CUGCCCAU
1280
AUGGGCAG UGAUG GCAUGCACUAUGC GCG ACUGUCAA
3469





1408
ACAGUGCU G CCCAUGUA
1281
UACAUGGG UGAUG GCAUGCACUAUGC GCG AGCACUGU
3470





1423
UACAAAGU G AACUCAUA
1282
UAUGAGUU UGAUG GCAUGCACUAUGC GCG ACUUUGUA
3471





1450
GUGGCAGU G ACAGGGAC
1283
GUCCCUGU UGAUG GCAUGCACUAUGC GCG ACUGCCAC
3472





1465
ACACACUC G CCAAAAGA
1284
UCUUUUGG UGAUG GCAUGCACUAUGC GCG GAGUGUGU
3473





1480
GAUUACCU G CAGCAGCU
1285
AGCUGCUG UGAUG GCAUGCACUAUGC GCG AGGUAAUC
3474





1508
GUCCAUCU G CAGCGGGC
1286
GCCCGCUG UGAUG GCAUGCACUAUGC GCG AGAUGGAC
3475





1520
CGGGCUUC G AUCGGCAU
1287
AUGCCGAU UGAUG GCAUGCACUAUGC GCG GAAGCCCG
3476





1536
UUUACUGU G AUUAGGAA
1288
UUCCUAAU UGAUG GCAUGCACUAUGC GCG ACAGUAAA
3477





1558
AUCCAACU G AUGGAUCU
1289
AGAUCCAU UGAUG GCAUGCACUAUGC GCG AGUUGGAU
3478





1567
AUGGAUCU G AAAUUGUG
1290
CACAAUUU UGAUG GCAUGCACUAUGC GCG AGAUCCAU
3479





1575
GAAAUUGU G CUGCUGAC
1291
GUCAGCAG UGAUG GCAUGCACUAUGC GCG ACAAUUUC
3480





1578
AUUGUGCU G CUGACGGA
1292
UCCGUCAG UGAUG GCAUGCACUAUGC GCG AGCACAAU
3481





1581
GUGCUGCU G ACGGAUGG
1293
CCAUCCGU UGAUG GCAUGCACUAUGC GCG AGCAGCAC
3482





1613
AAGUGGGU G CUUUAACG
1294
CGUUAAAG UGAUG GCAUGCACUAUGC GCG ACCCACUU
3483





1621
GCUUUAAC G AGGUCAAA
1295
UUUGACCU UGAUG GCAUGCACUAUGC GCG GUUAAAGC
3484





1639
AAAGUGGU G CCAUCAUC
1296
GAUGAUGG UGAUG GCAUGCACUAUGC GCG ACCACUUU
3485





1657
ACACAGUC G CUUUGGGG
1297
CCCCAAAG UGAUG GCAUGCACUAUGC GCG GACUGUGU
3486





1672
GGCCCUCU G CAGCUCAA
1298
UUGAGCUG UGAUG GCAUGCACUAUGC GCG AGAGGGCC
3487





1704
UCCAAAAU G ACAGGAGG
1299
CCUCCUGU UGAUG GCAUGCACUAUGC GCG AUUUUGGA
3488





1726
AGACAUAU G CUUCAGAU
1300
AUCUGAAG UGAUG GCAUGCACUAUGC GCG AUAUGUCU
3489





1759
GCCUCAUU G AUGCUUUU
1301
AAAAGCAU UGAUG GCAUGCACUAUGC GCG AAUGAGGC
3490





1762
UCAUUGAU G CUUUUGGG
1302
CCCAAAAG UGAUG GCAUGCACUAUGC GCG AUCAAUGA
3491





1805
CUCUCAGC G CUCCAUCC
1303
GGAUGGAG UGAUG GCAUGCACUAUGC GCG GCUGAGAG
3492





1819
UCCAGCUU G AGAGUAAG
1304
CUUACUCU UGAUG GCAUGCACUAUGC GCG AAGCUGGA
3493





1857
CAGUGGAU G AAUGGCAC
1305
GUGCCAUU UGAUG GCAUGCACUAUGC GCG AUCCACUG
3494





1869
GGCACAGU G AUCGUGGA
1306
UCCACGAU UGAUG GCAUGCACUAUGC GCG ACUGUGCC
3495





1923
UGGACAAC G CAGCCUCC
1307
GGAGGCUG UGAUG GCAUGCACUAUGC GCG GUUGUCCA
3496





2026
CAGGCAUU G CUAAGGUU
1308
AACCUUAG UGAUG GCAUGCACUAUGC GCG AAUGCCUG
3497





2055
UACAGUCU G CAAGCAAG
1309
CUUGCUUG UGAUG GCAUGCACUAUGC GCG AGACUGUA
3498





2076
CAAACCUU G ACCCUGAC
1310
GUCAGGGU UGAUG GCAUGCACUAUGC GCG AAGGUUUG
3499





2082
UUGACCCU G ACUGUCAC
1311
GUGACAGU UGAUG GCAUGCACUAUGC GCG AGGGUCAA
3500





2098
CGUCCCGU G CGUCCAAU
1312
AUUGGACG UGAUG GCAUGCACUAUGC GCG ACGGGACG
3501





2107
CGUCCAAU G CUACCCUG
1313
CAGGGUAG UGAUG GCAUGCACUAUGC GCG AUUGGACG
3502





2115
GCUACCCU G CCUCCAAU
1314
AUUGGAGG UGAUG GCAUGCACUAUGC GCG AGGGUAGC
3503





2130
AUUACAGU G ACUUCCAA
1315
UUGGAAGU UGAUG GCAUGCACUAUGC GCG ACUGUAAU
3504





2142
UCCAAAAC G AACAAGGA
1316
UCCUUGUU UGAUG GCAUGCACUAUGC GCG GUUUUGGA
3505





2185
UAGUUUAU G CAAAUAUU
1317
AAUAUUUG UGAUG GCAUGCACUAUGC GCG AUAAACUA
3506





2195
AAAUAUUC G CCAAGGAG
1318
CUCCUUGG UGAUG GCAUGCACUAUGC GCG GAAUAUUU
3507





2238
ACAGCCCU G AUUGAAUC
1319
GAUUCAAU UGAUG GCAUGCACUAUGC GCG AGGGCUGU
3508





2242
CCCUGAUU G AAUCAGUG
1320
CACUGAUU UGAUG GCAUGCACUAUGC GCG AAUCAGGG
3509





2250
GAAUCAGU G AAUGGAAA
1321
UUUCCAUU UGAUG GCAUGCACUAUGC GCG ACUGAUUC
3510





2296
GAGCAGGU G CUGAUGCU
1322
AGCAUCAG UGAUG GCAUGCACUAUGC GCG ACCUGCUC
3511





2299
CAGGUGCU G AUGCUACU
1323
AGUAGCAU UGAUG GCAUGCACUAUGC GCG AGCACCUG
3512





2302
GUGCUGAU G CUACUAAG
1324
CUUAGUAG UGAUG GCAUGCACUAUGC GCG AUCAGCAC
3513





2314
CUAAGGAU G ACGGUGUC
1325
GACACCGU UGAUG GCAUGCACUAUGC GCG AUCCUUAG
3514





2347
CAACUUAU G ACACGAAU
1326
AUUCGUGU UGAUG GCAUGCACUAUGC GCG AUAAGUUG
3515





2352
UAUGACAC G AAUGGUAG
1327
CUACCAUU UGAUG GCAUGCACUAUGC GCG GUGUCAUA
3516





2376
GUAAAAGU G CGGGCUCU
1328
AGAGCCCG UGAUG GCAUGCACUAUGC GCG ACUUUUAC
3517





2398
GAGUUAAC G CAGCCAGA
1329
UCUGGCUG UGAUG GCAUGCACUAUGC GCG GUUAACUC
3518





2415
CGGAGAGU G AUACCCCA
1330
UGGGGUAU UGAUG GCAUGCACUAUGC GCG ACUCUCCG
3519





2458
GCUGGAUU G AGAAUGAU
1331
AUCAUUCU UGAUG GCAUGCACUAUGC GCG AAUCCAGC
3520





2464
UUGAGAAU G AUGAAAUA
1332
UAUUUCAU UGAUG GCAUGCACUAUGC GCG AUUCUCAA
3521





2467
AGAAUGAU G AAAUACAA
1333
UUGUAUUU UGAUG GCAUGCACUAUGC GCG AUCAUUCU
3522





2494
CAAGACCU G AAAUUAAU
1334
AUUAAUUU UGAUG GCAUGCACUAUGC GCG AGGUCUUG
3523





2509
AUAAGGAU G AUGUUCAA
1335
UUGAACAU UGAUG GCAUGCACUAUGC GCG AUCCUUAU
3524





2572
UGGCUUCU G AUGUCCCA
1336
UGGGACAU UGAUG GCAUGCACUAUGC GCG AGAAGCCA
3525





2584
UCCCAAAU G CUCCCAUA
1337
UAUGGGAG UGAUG GCAUGCACUAUGC GCG AUUUGGGA
3526





2596
CCAUACCU G AUCUCUUC
1338
GAAGAGAU UGAUG GCAUGCACUAUGC GCG AGGUAUGG
3527





2623
AAAUCACC G ACCUGAAG
1339
CUUCAGGU UGAUG GCAUGCACUAUGC GCG GGUGAUUU
3528





2628
ACCGACCU G AAGGCGGA
1340
UCCGCCUU UGAUG GCAUGCACUAUGC GCG AGGUCGGU
3529





2664
AUUAAUCU G ACUUGGAC
1341
GUCCAAGU UGAUG GCAUGCACUAUGC GCG AGAUUAAU
3530





2686
CUGGGGAU G AUUAUGAC
1342
GUCAUAAU UGAUG GCAUGCACUAUGC GCG AUCCCCAG
3531





2692
AUGAUUAU G ACCAUGGA
1343
UCCAUGGU UGAUG GCAUGCACUAUGC GCG AUAAUCAU
3532





2723
UAUCAUUC G AAUAAGUA
1344
UACUUAUU UGAUG GCAUGCACUAUGC GCG GAAUGAUA
3533





2743
GUAUUCUU G AUCUCAGA
1345
UCUGAGAU UGAUG GCAUGCACUAUGC GCG AAGAAUAC
3534





2764
AGUUCAAU G AAUCUCUU
1346
AAGAGAUU UGAUG GCAUGCACUAUGC GCG AUUGAACU
3535





2778
CUUCAAGU G AAUACUAC
1347
GUAGUAUU UGAUG GCAUGCACUAUGC GCG ACUUGAAG
3536





2788
AUACUACU G CUCUCAUC
1348
GAUGAGAG UGAUG GCAUGCACUAUGC GCG AGUAGUAU
3537





2815
CCAACUCU G AGGAAGUC
1349
GACUUCCU UGAUG GCAUGCACUAUGC GCG AGAGUUGG
3538





2854
UUACUUUU G AAAAUGGC
1350
GCCAUUUU UGAUG GCAUGCACUAUGC GCG AAAAGUAA
3539





2878
UUUUCAUU G CUAUUCAG
1351
CUGAAUAG UGAUG GCAUGCACUAUGC GCG AAUGAAAA
3540





2893
AGGCUGUU G AUAAGGUC
1352
GACCUUAU UGAUG GCAUGCACUAUGC GCG AACAGCCU
3541





2902
AUAAGGUC G AUCUGAAA
1353
UUUCAGAU UGAUG GCAUGCACUAUGC GCG GACCUUAU
3542





2907
GUCGAUCU G AAAUCAGA
1354
UCUGAUUU UGAUG GCAUGCACUAUGC GCG AGAUCGAC
3543





2929
CCAACAUU G CACGAGUA
1355
UACUCGUG UGAUG GCAUGCACUAUGC GCG AAUGUUGG
3544





2933
CAUUGCAC G AGUAUCUU
1356
AAGAUACU UGAUG GCAUGCACUAUGC GCG GUGCAAUG
3545





2964
CAGACUCC G CCAGAGAC
1357
GUCUCUGG UGAUG GCAUGCACUAUGC GCG GGAGUCUG
3546





2983
CUAGUCCU G AUGAAACG
1358
CGUUUCAU UGAUG GCAUGCACUAUGC GCG AGGACUAG
3547





2986
GUCCUGAU G AAACGUCU
1359
AGACGUUU UGAUG GCAUGCACUAUGC GCG AUCAGGAC
3548





2995
AAACGUCU G CUCCUUGU
1360
ACAAGGAG UGAUG GCAUGCACUAUGC GCG AGACGUUU
3549





3078
GGAGAACU G CAGCUGUC
1361
GACAGCUG UGAUG GCAUGCACUAUGC GCG AGUUCUCC
3550





3101
CUAGGGCU G AAUUUUUG
1362
CAAAAAUU UGAUG GCAUGCACUAUGC GCG AGCCCUAG
3551





3145
CUUUUUUU G AUUAUAAA
1363
UUUAUAAU UGAUG GCAUGCACUAUGC GCG AAAAAAAG
3552





3191
UAGGGGGC G AUAUACUA
1364
UAGUAUAU UGAUG GCAUGCACUAUGC GCG GCCCCCUA
3553





3244
UAGGGGGC G AUAUACUA
1364
UAGUAUAU UGAUG GCAUGCACUAUGC GCG GCCCCCUA
3553





3281
UAGGGGGC G AUAAAAUA
1365
UAUUUUAU UGAUG GCAUGCACUAUGC GCG GCCCCCUA
3554





3294
AAUAAAAU G CUAAACAA
1366
UUGUUUAG UGAUG GCAUGCACUAUGC GCG AUUUUAUU
3555





27
AAAUGGAU G UGGAAUAU
1367
AUAUUCCA UGAUG GCAUGCACUAUGC GCG AUCCAUUU
3556





52
AUUUUCUU G UUUAAGGG
1368
CCCUUAAA UGAUG GCAUGCACUAUGC GCG AAGAAAAU
3557





75
GAAGAGGU G UUGAGGUU
1369
AACCUCAA UGAUG GCAUGCACUAUGC GCG ACCUCUUC
3558





86
GAGGUUAU G UCAAGCAU
1370
AUGCUUGA UGAUG GCAUGCACUAUGC GCG AUAACCUC
3559





155
AAGAUAUU G UUAUCAUU
1371
AAUGAUAA UGAUG GCAUGCACUAUGC GCG AAUAUCUU
3560





221
AAAGACCU G UGAUAAAC
1372
GUUUAUCA UGAUG GCAUGCACUAUGC GCG AGGUCUUU
3561





253
GGAAACGU G UGUGUAUA
1373
UAUAGACA UGAUG GCAUGCACUAUGC GCG ACGUUUCC
3562





255
AAACGUGU G UCUAUAUU
1374
AAUAUAGA UGAUG GCAUGCACUAUGC GCG ACACGUUU
3563





273
UCAUAUCU G UAUAUAUA
1375
UAUAUAUA UGAUG GCAUGCACUAUGC GCG AGAUAUGA
3564





344
AGGGAGAU G UACAGCAA
1376
UUGCUGUA UGAUG GCAUGCACUAUGC GCG AUCUCCCU
3565





373
AGAGUUCU G UGUUCAUC
1377
GAUGAACA UGAUG GCAUGCACUAUGC GCG AGAACUCU
3566





375
AGUUCUGU G UUCAUCUU
1378
AAGAUGAA UGAUG GCAUGCACUAUGC GCG ACAGAACU
3567





457
AAGGCAUU G UCGUUGCA
1379
UGCAACGA UGAUG GCAUGCACUAUGC GCG AAUGCCUU
3568





478
ACCCCAAU G UGCCAGAA
1380
UUCUGGCA UGAUG GCAUGCACUAUGC GCG AUUGGGGU
3569





537
GCAUCUCU G UAUCUGUU
1381
AACAGAUA UGAUG GCAUGCACUAUGC GCG AGAGAUGC
3570





543
CUGUAUCU G UUUGAAGC
1382
GCUUCAAA UGAUG GCAUGCACUAUGC GCG AGAUACAG
3571





580
UCAAAAAU G UUGCCAUU
1383
AAUGGCAA UGAUG GCAUGCACUAUGC GCG AUUUUUGA
3572





625
CUGACUAU G UGAGACCA
1384
UGGUCUCA UGAUG GCAUGCACUAUGC GCG AUAGUCAG
3573





661
AUGCUGAU G UUCUGGUU
1385
AACCAGAA UGAUG GCAUGCACUAUGC GCG AUCAGCAU
3574





725
GGGCAACU G UGGAGAGA
1386
UCUCUCCA UGAUG GCAUGCACUAUGC GCG AGUUGCCC
3575





814
AGGCAUUU G UCCAUGAG
1387
CUCAUGGA UGAUG GCAUGCACUAUGC GCG AAAUGCCU
3576





911
AGUAAGAU G UUCAGCAG
1388
CUGCUGAA UGAUG GCAUGCACUAUGC GCG AUCUUACU
3577





937
GUACAAAU G UAGUAAAG
1389
CUUUACUA UGAUG GCAUGCACUAUGC GCG AUUUGUAC
3578





950
AAAGAAGU G UCAGGGAG
1390
CUCCCUGA UGAUG GCAUGCACUAUGC GCG ACUUCUUU
3579





965
AGGCAGCU G UUACACCA
1391
UGGUGUAA UGAUG GCAUGCACUAUGC GCG AGCUGCCU
3580





1019
AAAAGGAU G UGAGUUUG
1392
CAAACUCA UGAUG GCAUGCACUAUGC GCG AUCCUUUU
3581





1027
GUGAGUUU G UUCUCCAA
1393
UUGGAGAA UGAUG GCAUGCACUAUGC GCG AAACUCAC
3582





1065
UCUAUAAU G UUUGCACA
1394
UGUGCAAA UGAUG GCAUGCACUAUGC GCG AUUAUAGA
3583





1078
CACAACAU G UUGAUUCU
1395
AGAAUCAA UGAUG GCAUGCACUAUGC GCG AUGUUGUG
3584





1100
UGAAUUCU G UACAGAAC
1396
GUUCUGUA UGAUG GCAUGCACUAUGC GCG AGAAUUCA
3585





1270
AAAGAAUU G UGUGUUUA
1397
UAAACACA UGAUG GCAUGCACUAUGC GCG AAUUCUUU
3586





1272
AGAAUUGU G UGUUUAGU
1398
ACUAAACA UGAUG GCAUGCACUAUGC GCG ACAAUUCU
3587





1274
AAUUGUGU G UUUAGUCC
1399
GGACUAAA UGAUG GCAUGCACUAUGC GCG ACACAAUU
3588





1414
CUGCCCAU G UACAAAGU
1400
ACUUUGUA UGAUG GCAUGCACUAUGC GCG AUGOGGAG
3589





1534
CAUUUACU G UGAUUAGG
1401
CCUAAUCA UGAUG GCAUGCACUAUGC GCG AGUAAAUG
3590





1573
CUGAAAUU G UGCUGCUG
1402
CAGCAGCA UGAUG GCAUGCACUAUGC GCG AAUUUCAG
3591





1695
GAGGAGCU G UCCAAAAU
1403
AUUUUGGA UGAUG GCAUGCACUAUGC GCG AGCUCCUC
3592





1795
AUGGAGCU G UCUCUCAG
1404
CUGAGAGA UGAUG GCAUGCACUAUGC GCG AGCUCCAU
3593





1902
GACACUUU G UUUCUUAU
1405
AUAAGAAA UGAUG GCAUGCACUAUGC GCG AAAGUGUC
3594





1978
GUGGCUUU G UAGUGGAC
1406
GUCCACUA UGAUG GCAUGCACUAUGC GCG AAAGCCAC
3595





2086
CCCUGACU G UCACGUCC
1407
GGACGUGA UGAUG GCAUGCACUAUGC GCG AGUCAGGG
3596





2227
GGGCCAGU G UCACAGCC
1408
GGCUGUGA UGAUG GCAUGCACUAUGC GCG ACUGGCCC
3597





2320
AUGACGGU G UCUACUCA
1409
UGAGUAGA UGAUG GCAUGCACUAUGC GCG ACCGUCAU
3598





2368
GAUACAGU G UAAAAGUG
1410
CACUUUUA UGAUG GCAUGCACUAUGC GCG ACUGUAUC
3599





2439
GGAGCACU G UACAUACC
1411
GGUAUGUA UGAUG GCAUGCACUAUGC GCG AGUGCUCC
3600





2512
AGGAUGAU G UUCAACAC
1412
GUGUUGAA UGAUG GCAUGCACUAUGC GCG AUCAUCCU
3601





2529
AAGCAAGU G UGUUUCAG
1413
CUGAAACA UGAUG GCAUGCACUAUGC GCG ACUUGCUU
3602





2531
GCAAGUGU G UUCAGCA
1414
UGCUGAAA UGAUG GCAUGCACUAUGC GCG ACACUUGC
3603





2563
GCUCAUUU G UGGCUUCU
1415
AGAAGCCA UGAUG GCAUGCACUAUGC GCG AAAUGAGC
3604





2575
CUUCUGAU G UCCCAAAU
1416
AUUUGGGA UGAUG GCAUGCACUAUGC GCG AUCAGAAG
3605





2829
GUCUUUUU G UUUAAACC
1417
GGUUUAAA UGAUG GCAUGCACUAUGC GCG AAAAAGAC
3606





2890
UUCAGGCU G UUGAUAAG
1418
CUUAUCAA UGAUG GCAUGCACUAUGC GCG AGCCUGAA
3607





2943
GUAUCUUU G UUUAUUCC
1419
GGAAUAAA UGAUG GCAUGCACUAUGC GCG AAAGAUAC
3608





3002
UGCUCCUU G UCCUAAUA
1420
UAUUAGGA UGAUG GCAUGCACUAUGC GCG AAGGAGCA
3609





3057
AAAAUUAU G UGGAAGUG
1421
CACUUCCA UGAUG GCAUGCACUAUGC GCG AUAAUUUU
3610





3084
CUGCAGCU G UCAAUAGC
1422
GCUAUUGA UGAUG GCAUGCACUAUGC GCG AGCUGCAG
3611





3109
GAAUUUUU G UCAGAUAA
1423
UUAUCUGA UGAUG GCAUGCACUAUGC GCG AAAAAUUC
3612





3166
UCUAAAAU G UAUUUUAG
1424
CUAAAAUA UGAUG GCAUGCACUAUGC GCG AUUUUAGA
3613





3182
GACUUCCU G UAGGGGGC
1425
GCCCCCUA UGAUG GCAUGCACUAUGC GCG AGGAAGUC
3614





3272
GACUUCCU G UAGGGGGC
1425
GCCCCCUA UGAUG GCAUGCACUAUGC GCG AGGAAGUC
3614





3203
UACUAAAU G UAUAUAGU
1426
ACUAUAUA UGAUG GCAUGCACUAUGC GCG AUUUAGUA
3615





3227
UACUAAAU G UAUUCCUG
1427
CAGGAAUA UGAUG GCAUGCACUAUGC GCG AUUUAGUA
3616





3235
GUAUUCCU G UAGGGGGC
1428
GCCCCCUA UGAUG GCAUGCACUAUGC GCG AGGAAUAC
3617





3256
UACUAAAU G UAUUUUAG
1429
CUAAAAUA UGAUG GCAUGCACUAUGC GCG AUUUAGUA
3618






Input Sequence = NM_001285. Cut Site = YG/M or UG/U.




Arm Length = 8. Core Sequence = UGAUG GCAUGCACUAUGC GCG




NM_001285 (Homo sapiens chloride channel, calcium activated, 1 (CLCA 1) mRNA, 3311 bp)








[0193]

6





TABLE VI










Human CLCA1 Zinzyme and Target Sequence 249.021













Seq

Rz Seq


Pos
Substrate
ID
Zinzyme
ID














134
ACAAGUAC G CAAUUUGA
1215
UCAAAUUG GCCGAAAGGCGAGUGAGGUCU GUACUUGU
3619





312
CGUAACCC G CAUUUUCC
1220
GGAAAAUG GCCGAAAGGCGAGUGAGGUCU GGGUUACG
3620





463
UUGUCGUU G CAAUCGAC
1225
GUCGAUUG GCCGAAAGGCGAGUGAGGUCU AACGACAA
3621





480
CCCAAUGU G CCAGAAGA
1227
UCUUCUGG GCCGAAAGGCGAGUGAGGUCU ACAUUGGG
3622





583
AAAAUGUU G CCAUUUUG
1232
CAAAAUGG GCCGAAAGGCGAGUGAGGUCU AACAUUUU
3623





655
ACAAAAAU G CUGAUGUU
1238
AACAUCAG GCCGAAAGGCGAGUGAGGUCU AUUUUUGU
3624





670
UUCUGGUU G CUGAGUCU
1240
AGACUCAG GCCGAAAGGCGAGUGAGGUCU AACCAGAA
3625





769
AUUUCAUU G CAGGAAAA
1247
UUUUCCUG GCCGAAAGGCGAGUGAGGUCU AAUGAAAU
3626





980
CAAAAGAU G CACAUUCA
1255
UGAAUGUG GCCGAAAGGCGAGUGAGGUCU AUCUUUUG
3627





1040
CCAAUCCC G CCAGACGG
1258
CCGUCUGG GCCGAAAGGCGAGUGAGGUCU GGGAUUGG
3628





1069
UAAUGUUU G CACAACAU
1259
AUGUUGUG GCCGAAAGGCGAGUGAGGUCU AAACAUUA
3629





1151
UCAAAAAU G CAAUCUCC
1262
GGAGAUUG GCCGAAAGGCGAGUGAGGUCU AUUUUUGA
3630





1248
UUCUCAUU G CUGCAGAU
1268
AUCUGCAG GCCGAAAGGCGAGUGAGGUCU AAUGAGAA
3631





1251
UCAUUGCU G CAGAUUGG
1269
CCAAUCUG GCCGAAAGGCGAGUGAGGUCU AGCAAUGA
3632





1316
UGGUAACC G CCUCAAUC
1272
GAUUGAGG GCCGAAAGGCGAGUGAGGUCU GGUUACCA
3633





1353
CUUUUCCU G CUGCAGAC
1275
GUCUGCAG GCCGAAAGGCGAGUGAGGUCU AGGAAAAG
3634





1356
UUCCUGCU G CAGACAGU
1276
ACUGUCUG GCCGAAAGGCGAGUGAGGUCU AGCAGGAA
3635





1405
UUGACAGU G CUGCCCAU
1280
AUGGGCAG GCCGAAAGGCGAGUGAGGUCU ACUGUCAA
3636





1408
ACAGUGCU G CCCAUGUA
1281
UACAUGGG GCCGAAAGGCGAGUGAGGUCU AGCACUGU
3637





1465
ACACACUC G CCAAAAGA
1284
UCUUUUGG GCCGAAAGGCGAGUGAGGUCU GAGUGUGU
3638





1480
GAUUACCU G CAGCAGCU
1285
AGCUGCUG GCCGAAAGGCGAGUGAGGUCU AGGUAAUC
3639





1508
GUCCAUCU G CAGCGGGC
1286
GCCCGCUG GCCGAAAGGCGAGUGAGGUCU AGAUGGAC
3640





1575
GAAAUUGU G CUGCUGAC
1291
GUCAGCAG GCCGAAAGGCGAGUGAGGUCU ACAAUUUC
3641





1578
AUUGUGCU G CUGACGGA
1292
UCCGUCAG GCCGAAAGGCGAGUGAGGUCU AGCACAAU
3642





1613
AAGUGGGU G CUUUAACG
1294
CGUUAAAG GCCGAAAGGCGAGUGAGGUCU ACCCACUU
3643





1639
AAAGUGGU G CCAUCAUC
1296
GAUGAUGG GCCGAAAGGCGAGUGAGGUCU ACCACUUU
3644





1657
ACACAGUC G CUUUGGGG
1297
CCCCAAAG GCCGAAAGGCGAGUGAGGUCU GACUGUGU
3645





1672
GGCCCUCU G CAGCUCAA
1298
UUGAGCUG GCCGAAAGGCGAGUGAGGUCU AGAGGGCC
3646





1726
AGACAUAU G CUUCAGAU
1300
AUCUGAAG GCCGAAAGGCGAGUGAGGUCU AUAUGUCU
3647





1762
UCAUUGAU G CUUUUGGG
1302
CCCAAAAG GCCGAAAGGCGAGUGAGGUCU AUCAAUGA
3648





1805
CUCUCAGC G CUCCAUCC
1303
GGAUGGAG GCCGAAAGGCGAGUGAGGUCU GCUGAGAG
3649





1923
UGGACAAC G CAGCCUCC
1307
GGAGGCUG GCCGAAAGGCGAGUGAGGUCU GUUGUCCA
3650





2026
CAGGCAUU G CUAAGGUU
1308
AACCUUAG GCCGAAAGGCGAGUGAGGUCU AAUGCCUG
3651





2055
UACAGUCU G CAAGCAAG
1309
CUUGCUUG GCCGAAAGGCGAGUGAGGUCU AGACUGUA
3652





2098
CGUCCCGU G CGUCCAAU
1312
AUUGGACG GCCGAAAGGCGAGUGAGGUCU ACGGGACG
3653





2107
CGUCCAAU G CUACCCUG
1313
CAGGGUAG GCCGAAAGGCGAGUGAGGUCU AUUGGACG
3654





2115
GCUACCCU G CCUCCAAU
1314
AUGGAGG GCCGAAAGGCGAGUGAGGUCU AGGGUAGC
3655





2185
UAGUUUAU G CAAAUAUU
1317
AAUAUUUG GCCGAAAGGCGAGUGAGGUCU AUAAACUA
3656





2195
AAAUAUUC G CCAAGGAG
1318
CUCCUUGG GCCGAAAGGCGAGUGAGGUCU GAAUAUUU
3657





2296
GAGCAGGU G CUGAUGCU
1322
AGCAUCAG GCCGAAAGGCGAGUGAGGUCU ACCUGCUC
3658





2302
GUGCUGAU G CUACUAAG
1324
CUUAGUAG GCCGAAAGGCGAGUGAGGUCU AUCAGCAC
3659





2376
GUAAAAGU G CGGGCUCU
1328
AGAGCCCG GCCGAAAGGCGAGUGAGGUCU ACUUUUAC
3660





2398
GAGUUAAC G CAGCCAGA
1329
UCUGGCUG GCCGAAAGGCGAGUGAGGUCU GUUAACUC
3661





2584
UCCCAAAU G CUCCCAUA
1337
UAUGGGAG GCCGAAAGGCGAGUGAGGUCU AUUUGGGA
3662





2788
AUACUACU G CUCUCAUC
1348
GAUGAGAG GCCGAAAGGCGAGUGAGGUCU AGUAGUAU
3663





2878
UUUUCAUU G CUAUUCAG
1351
CUGAAUAG GCCGAAAGGCGAGUGAGGUCU AAUGAAAA
3664





2929
CCAACAUU G CACGAGUA
1355
UACUCGUG GCCGAAAGGCGAGUGAGGUCU AAUGUUGG
3665





2964
CAGACUCC G CCAGAGAC
1357
GUCUCUGG GCCGAAAGGCGAGUGAGGUCU GGAGUCUG
3666





2995
AAACGUCU G CUCCUUGU
1360
ACAAGGAG GCCGAAAGGCGAGUGAGGUCU AGACGUUU
3667





3078
GGAGAACU G CAGCUGUC
1361
GACAGCUG GCCGAAAGGCGAGUGAGGUCU AGUUCUCC
3668





3294
AAUAAAAU G CUAAACAA
1366
UUGUUUAG GCCGAAAGGCGAGUGAGGUCU AUUUUAUU
3669





27
AAAUGGAU G UGGAAUAU
1367
AUAUUCCA GCCGAAAGGCGAGUGAGGUCU AUCCAUUU
3670





52
AUUUUCUU G UUUAAGGG
1368
CCCUUAAA GCCGAAAGGCGAGUGAGGUCU AAGAAAAU
3671





75
GAAGAGGU G UUGAGGUU
1369
AACCUCAA GCCGAAAGGCGAGUGAGGUCU ACCUCUUC
3672





86
GAGGUUAU G UCAAGCAU
1370
AUGCUUGA GCCGAAAGGCGAGUGAGGUCU AUAACCUC
3673





155
AAGAUAUU G UUAUCAUU
1371
AAUGAUAA GCCGAAAGGCGAGUGAGGUCU AAUAUCUU
3674





221
AAAGACCU G UGAUAAAC
1372
GUUUAUCA GCCGAAAGGCGAGUGAGGUCU AGGUCUUU
3675





253
GGAAACGU G UGUCUAUA
1373
UAUAGACA GCCGAAAGGCGAGUGAGGUCU ACGUUUCC
3676





255
AAACGUGU G UCUAUAUU
1374
AAUAUAGA GCCGAAAGGCGAGUGAGGUCU ACACGUUU
3677





273
UCAUAUCU G UAUAUAUA
1375
UAUAUAUA GCCGAAAGGCGAGUGAGGUCU AGAUAUGA
3678





344
AGGGAGAU G UACAGCAA
1376
UUGCUGUA GCCGAAAGGCGAGUGAGGUCU AUCUCCCU
3679





373
AGAGUUCU G UGUUCAUC
1377
GAUGAACA GCCGAAAGGCGAGUGAGGUCU AGAACUCU
3680





375
AGUUCUGU G UUCAUCUU
1378
AAGAUGAA GCCGAAAGGCGAGUGAGGUCU ACAGAACU
3681





457
AAGGCAUU G UCGUUGCA
1379
UGCAACGA GCCGAAAGGCGAGUGAGGUCU AAUGCCUU
3682





478
ACCCCAAU G UGCCAGAA
1380
UUCUGGCA GCCGAAAGGCGAGUGAGGUCU AUUGGGGU
3683





537
GCAUCUCU G UAUCUGUU
1381
AACAGAUA GCCGAAAGGCGAGUGAGGUCU AGAGAUGC
3684





543
CUGUAUCU G UUUGAAGC
1382
GCUUCAAA GCCGAAAGGCGAGUGAGGUCU AGAUACAG
3685





580
UCAAAAAU G UUGCCAUU
1383
AAUGGCAA GCCGAAAGGCGAGUGAGGUCU AUUUUUGA
3686





625
CUGACUAU G UGAGACCA
1384
UGGUCUCA GCCGAAAGGCGAGUGAGGUCU AUAGUCAG
3687





661
AUGCUGAU G UUCUGGUU
1385
AACCAGAA GCCGAAAGGCGAGUGAGGUCU AUCAGCAU
3688





725
GGGCAACU G UGGAGAGA
1386
UCUCUCCA GCCGAAAGGCGAGUGAGGUCU AGUUGCCC
3689





814
AGGCAUUU G UCCAUGAG
1387
CUCAUGGA GCCGAAAGGCGAGUGAGGUCU AAAUGCCU
3690





911
AGUAAGAU G UUCAGCAG
1388
CUGCUGAA GCCGAAAGGCGAGUGAGGUCU AUCUUACU
3691





937
GUACAAAU G UAGUAAAG
1389
CUUUACUA GCCGAAAGGCGAGUGAGGUCU AUUUUAC
3692





950
AAAGAAGU G UCAGGGAG
1390
CUCCCUGA GCCGAAAGGCGAGUGAGGUCU ACUUCUUU
3693





965
AGGCAGCU G UUACACCA
1391
UGGUGUAA GCCGAAAGGCGAGUGAGGUCU AGCUGCCU
3694





1019
AAAAGGAU G UGAGUUUG
1392
CAAACUCA GCCGAAAGGCGAGUGAGGUCU AUCCUUUU
3695





1027
GUGAGUUU G UUCUCCAA
1393
UUGGAGAA GCCGAAAGGCGAGUGAGGUCU AAACUCAC
3696





1065
UCUAUAAU G UUUGCACA
1394
UGUGCAAA GCCGAAAGGCGAGUGAGGUCU AUUAUAGA
3697





1078
CACAACAU G UUGAUUCU
1395
AGAAUCAA GCCGAAAGGCGAGUGAGGUCU AUGUUGUG
3698





1100
UGAAUUCU G UACAGAAC
1396
GUUCUGUA GCCGAAAGGCGAGUGAGGUCU AGAAUUCA
3699





1270
AAAGAAUU G UGUGUUUA
1397
UAAACACA GCCGAAAGGCGAGUGAGGUCU AAUUCUUU
3700





1272
AGAAUUGU G UGUUUAGU
1398
ACUAAACA GCCGAAAGGCGAGUGAGGUCU ACAAUUCU
3701





1274
AAUUGUGU G UUUAGUCC
1399
GGACUAAA GCCGAAAGGCGAGUGAGGUCU ACACAAUU
3702





1414
CUGCCCAU G UACAAAGU
1400
ACUUUGUA GCCGAAAGGCGAGUGAGGUCU AUGGGCAG
3703





1534
CAUUUACU G UGAUUAGG
1401
CCUAAUCA GCCGAAAGGCGAGUGAGGUCU AGUAAAUG
3704





1573
CUGAAAUU G UGCUGCUG
1402
CAGGAGGA GCCGAAAGGCGAGUGAGGUCU AAUUUCAG
3705





1695
GAGGAGCU G UCCAAAAU
1403
AUUUUGGA GCCGAAAGGCGAGUGAGGUCU AGCUCCUC
3706





1795
AUGGAGCU G UCUCUCAG
1404
CUGAGAGA GCCGAAAGGCGAGUGAGGUCU AGCUCCAU
3707





1902
GACACUUU G UUUCUUAU
1405
AUAAGAAA GCCGAAAGGCGAGUGAGGUCU AAAGUGUC
3708





1978
GUGGCUUU G UAGUGGAC
1406
GUCCACUA GCCGAAAGGCGAGUGAGGUCU AAAGCCAC
3709





2086
CCCUGACU G UCACGUCC
1407
GGACGUGA GCCGAAAGGCGAGUGAGGUCU AGUCAGGG
3710





2227
GGGCCAGU G UCACAGCC
1408
GGCUGUGA GCCGAAAGGCGAGUGAGGUCU ACUGGCCC
3711





2320
AUGACGGU G UCUACUCA
1409
UGAGUAGA GCCGAAAGGCGAGUGAGGUCU ACCGUCAU
3712





2368
GAUACAGU G UAAAGUG
1410
CACUUUUA GCCGAAAGGCGAGUGAGGUCU ACUGUAUC
3713





2439
GGAGCACU G UACAUACC
1411
GGUAUGUA GCCGAAAGGCGAGUGAGGUCU AGUGCUCC
3714





2512
AGGAUGAU G UUCAACAC
1412
GUGUUGAA GCCGAAAGGCGAGUGAGGUCU AUCAUCCU
3715





2529
AAGCAAGU G UGUUUCAG
1413
CUGAAACA GCCGAAAGGCGAGUGAGGUCU ACUUGCUU
3716





2531
GCAAGUGU G UUUCAGCA
1414
UGCUGAAA GCCGAAAGGCGAGUGAGGUCU ACACUUGC
3717





2563
GCUCAUUU G UGGCUUCU
1415
AGAAGCCA GCCGAAAGGCGAGUGAGGUCU AAAUGAGC
3718





2575
CUUCUGAU G UCCCAAAU
1416
AUUUGGGA GCCGAAAGGCGAGUGAGGUCU AUCAGAAG
3719





2829
GUCUUUUU G UUUAUACC
1417
GGUUUAAA GCCGAAAGGCGAGUGAGGUCU AAAAAGAC
3720





2890
UUCAGGCU G UUGAUAAG
1418
CUUAUCAA GCCGAAAGGCGAGUGAGGUCU AGCCUGAA
3721





2943
GUAUCUUU G UUUAUUCC
1419
GGAAUAAA GCCGAAAGGCGAGUGAGGUCU AAAGAUAC
3722





3002
UGCUCCUU G UCCUAAUA
1420
UAUUAGGA GCCGAAAGGCGAGUGAGGUCU AAGGAGCA
3723





3057
AAAAUUAU G UGGAAGUG
1421
CACUUCCA GCCGAAAGGCGAGUGAGGUCU AUAAUUUU
3724





3084
CUGCAGCU G UCAAUAGC
1422
GCUAUUGA GCCGAAAGGCGAGUGAGGUCU AGCUGCAG
3725





3109
GAAUUUUU G UCAGAUAA
1423
UUAUCUGA GCCGAAAGGCGAGUGAGGUCU AAAAAUUC
3726





3166
UCUAAAAU G UAUUUUAG
1424
CUAAAAUA GCCGAAAGGCGAGUGAGGUCU AUUUUAGA
3727





3182
GACUUCCU G UAGGGGGC
1425
GCCCCCUA GCCGAAAGGCGAGUGAGGUCU AGGAAGUC
3728





3272
GACUUCCU G UAGGGGGC
1425
GCCCCCUA GCCGAAAGGCGAGUGAGGUCU AGGAAGUC
3728





3203
UACUAAAU G UAUAUAGU
1426
ACUAUAUA GCCGAAAGGCGAGUGAGGUCU AUUUAGUA
3729





3227
UACUAAAU G UAUUCCUG
1427
CAGGAAUA GCCGAAAGGCGAGUGAGGUCU AUUUAGUA
3730





3235
GUAUUCCU G UAGGGGGC
1428
GCCCCCUA GCCGAAAGGCGAGUGAGGUCU AGGAAUAC
3731





3256
UACUAAAU G UAUUUUAG
1429
CUAAAAUA GCCGAAAGGCGAGUGAGGUCU AUUUAGUA
3732





15
UGCUUUUG G UACAAAUG
1430
CAUUUGUA GCCGAAAGGCGAGUGAGGUCU CAAAAGCA
3733





63
UAAGGGGA G CAUGAAGA
1431
UCUUCAUG GCCGAAAGGCGAGUGAGGUCU UCCCCUUA
3734





73
AUGAAGAG G UGUUGAGG
1432
CCUCAACA GCCGAAAGGCGAGUGAGGUCU CUCUUCAU
3735





81
GUGUUGAG G UUAUGUCA
1433
UGACAUAA GCCGAAAGGCGAGUGAGGUCU CUCAACAC
3736





91
UAUGUCAA G CAUCUGGC
1434
GCCAGAUG GCCGAAAGGCGAGUGAGGUCU UUGACAUA
3737





98
AGCAUCUG G CACAGCUG
1435
CAGCUGUG GCCGAAAGGCGAGUGAGGUCU CAGAUGCU
3738





103
CUGGCACA G CUGAAGGC
1436
GCCUUCAG GCCGAAAGGCGAGUGAGGUCU UGUGCCAG
3739





110
AGCUGAAG G CAGAUGGA
1437
UCCAUCUG GCCGAAAGGCGAGUGAGGUCU CUUCAGCU
3740





130
AUUUACAA G UACGCAAU
1438
AUUGCGUA GCCGAAAGGCGAGUGAGGUCU UUGUAAAU
3741





182
AGACAAGA G CAAUAGUA
1439
UACUAUUG GCCGAAAGGCGAGUGAGGUCU UCUUGUCU
3742





188
GAGCAAUA G UAAAACAC
1440
GUGUUUUA GCCGAAAGGCGAGUGAGGUCU UAUUGCUC
3743





202
CACAUCAG G UCAGGGGG
1441
CCCCCUGA GCCGAAAGGCGAGUGAGGUCU CUGAUGUG
3744





210
GUCAGGGG G UUAAAGAC
1442
GUCUUUAA GCCGAAAGGCGAGUGAGGUCU CCCCUGAC
3745





242
UCCGAUAA G UUGGAAAC
1443
GUUUCCAA GCCGAAAGGCGAGUGAGGUCU UUAUCGGA
3746





251
UUGGAAAC G UGUGUCUA
1444
UAGACACA GCCGAAAGGCGAGUGAGGUCU GUUUCCAA
3747





287
AUAUAAUG G UAAAGAAA
1445
UUUCUUUA GCCGAAAGGCGAGUGAGGUCU CAUUAUAU
3748





305
ACACCUUC G UAACCCGC
1446
GCGGGUUA GCCGAAAGGCGAGUGAGGUCU GAAGGUGU
3749





349
GAUGUACA G CAAUGGGG
1447
CCCCAUUG GCCGAAAGGCGAGUGAGGUCU UGUACAUC
3750





357
GCAAUGGG G CCAUUUAA
1448
UUAAAUGG GCCGAAAGGCGAGUGAGGUCU CCCAUUGC
3751





368
AUUUAAGA G UUCUGUGU
1449
ACACAGAA GCCGAAAGGCGAGUGAGGUCU UCUUAAAU
3752





406
UAGAAGGG G CCCUGAGU
1450
ACUCAGGG GCCGAAAGGCGAGUGAGGUCU CCCUUCUA
3753





413
GGCCCUGA G UAAUUCAC
1451
GUGAAUUA GCCGAAAGGCGAGUGAGGUCU UCAGGGCC
3754





429
CUCAUUCA G CUGAACAA
1452
UUGUUCAG GCCGAAAGGCGAGUGAGGUCU UGAAUGAG
3755





443
CAACAAUG G CUAUGAAG
1453
CUUCAUAG GCCGAAAGGCGAGUGAGGUCU CAUUGUUG
3756





452
CUAUGAAG G CAUUGUCG
1454
CGACAAUG GCCGAAAGGCGAGUGAGGUCU CUUCAUAG
3757





460
GCAUUGUC G UUGCAAUC
1455
GAUUGCAA GCCGAAAGGCGAGUGAGGUCU GACAAUGC
3758





520
AGGACAUG G UGACCCAG
1456
CUGGGUCA GCCGAAAGGCGAGUGAGGUCU CAUGUCCU
3759





529
UGACCCAG G CAUCUCUG
1457
CAGAGAUG GCCGAAAGGCGAGUGAGGUCU CUGGGUCA
3760





550
UGUUUGAA G CUACAGGA
1458
UCCUGUAG GCCGAAAGGCGAGUGAGGUCU UUCAAACA
3761





561
ACAGGAAA G CGAUUUUA
1459
UAAAAUCG GCCGAAAGGCGAGUGAGGUCU UUUCCUGU
3762





616
AGACAAAG G CUGACUAU
1460
AUAGUCAG GCCGAAAGGCGAGUGAGGUCU CUUUGUCU
3763





667
AUGUUCUG G UUGCUGAG
1461
CUCAGCAA GCCGAAAGGCGAGUGAGGUCU CAGAACAU
3764





675
GUUGCUGA G UCUACUCC
1462
GGAGUAGA GCCGAAAGGCGAGUGAGGUCU UCAGCAAC
3765





689
UCCUCCAG G UAAUGAUG
1463
CAUCAUUA GCCGAAAGGCGAGUGAGGUCU CUGGAGGA
3766





711
UACACUGA G CAGAUGGG
1464
CCCAUCUG GCCGAAAGGCGAGUGAGGUCU UCAGUGUA
3767





719
GCAGAUGG G CAACUGUG
1465
CACAGUUG GCCGAAAGGCGAGUGAGGUCU CCAUCUGC
3768





737
AGAGAAGG G UGAAAGGA
1466
UCCUUUCA GCCGAAAGGCGAGUGAGGUCU CCUUCUCU
3769





780
GGAAAAAA G UUAGCUGA
1467
UCAGCUAA GCCGAAAGGCGAGUGAGGUCU UUUUUUCC
3770





784
AAAAGUUA G CUGAAUAU
1468
AUAUUCAG GCCGAAAGGCGAGUGAGGUCU UAACUUUU
3771





803
ACCACAAG G UAAGGCAU
1469
AUGCCUUA GCCGAAAGGCGAGUGAGGUCU CUUGUGGU
3772





808
AAGGUAAG G CAUUUGUC
1470
GACAAAUG GCCGAAAGGCGAGUGAGGUCU CUUACCUU
3773





822
GUCCAUGA G UGGGCUCA
1471
UGAGCCCA GCCGAAAGGCGAGUGAGGUCU UCAUGGAC
3774





826
AUGAGUGG G CUCAUCUA
1472
UAGAUGAG GCCGAAAGGCGAGUGAGGUCU CCACUCAU
3775





844
GAUGGGGA G UAUUUGAC
1473
GUCAAAUA GCCGAAAGGCGAGUGAGGUCU UCCCCAUC
3776





855
UUUGACGA G UACAAUAA
1474
UUAUUGUA GCCGAAAGGCGAGUGAGGUCU UCGUCAAA
3777





901
GAAUACAA G CAGUAAGA
1475
UCUUACUG GCCGAAAGGCGAGUGAGGUCU UUGUAUUC
3778





904
UACAAGCA G UAAGAUGU
1476
ACAUCUUA GCCGAAAGGCGAGUGAGGUCU UGCUUGUA
3779





916
GAUGUUCA G CAGGUAUU
1477
AAUACCUG GCCGAAAGGCGAGUGAGGUCU UGAACAUC
3780





920
UUCAGCAG G UAUUACUG
1478
CAGUAAUA GCCGAAAGGCGAGUGAGGUCU CUGCUGAA
3781





929
UAUUACUG G UACAAAUG
1479
CAUUUGUA GCCGAAAGGCGAGUGAGGUCU CAGUAAUA
3782





940
CAAAUGUA G UAAAGAAG
1480
CUUCUUUA GCCGAAAGGCGAGUGAGGUCU UACAUUUG
3783





948
GUAAAGAA G UGUCAGGG
1481
CCCUGACA GCCGAAAGGCGAGUGAGGUCU UUCUUUAC
3784





959
UCAGGGAG G CAGCUGUU
1482
AACAGCUG GCCGAAAGGCGAGUGAGGUCU CUCCCUGA
3785





962
GGGAGGCA G CUGUUACA
1483
UGUAACAG GCCGAAAGGCGAGUGAGGUCU UGCCUCCC
3786





994
UCAAUAAA G UUACAGGA
1484
UCCUGUAA GCCGAAAGGCGAGUGAGGUCU UUUAUUGA
3787





1023
GGAUGUGA G UUUGUUCU
1485
AGAACAAA GCCGAAAGGCGAGUGAGGUCU UCACAUCC
3788





1054
CGGAGAAG G CUUCUAUA
1486
UAUAGAAG GCCGAAAGGCGAGUGAGGUCU CUUCUCCG
3789





1090
AUUCUAUA G UUGAAUUC
1487
GAAUUCAA GCCGAAAGGCGAGUGAGGUCU UAUAGAAU
3790





1126
ACAAAGAA G CUCCAAAC
1488
GUUUGGAG GCCGAAAGGCGAGUGAGGUCU UUCUUUGU
3791





1137
CCAAACAA G CAAAAUCA
1489
UGAUUUUG GCCGAAAGGCGAGUGAGGUCU UUGUUUGG
3792





1163
UCUCCGAA G CACAUGGG
1490
CCCAUGUG GCCGAAAGGCGAGUGAGGUCU UUCGGAGA
3793





1174
CAUGGGAA G UGAUCCGU
1491
ACGGAUCA GCCGAAAGGCGAGUGAGGUCU UUCCCAUG
3794





1181
AGUGAUCC G UGAUUCUG
1492
CAGAAUCA GCCGAAAGGCGAGUGAGGUCU GGAUCACU
3795





1224
ACAACACA G CCACCAAA
1493
UUUGGUGG GCCGAAAGGCGAGUGAGGUCU UGUGUUGU
3796





1279
UGUGUUUA G UCCUUGAC
1494
GUCAAGGA GCCGAAAGGCGAGUGAGGUCU UAAACACA
3797





1298
AUCUGGAA G CAUGGCGA
1495
UCGCCAUG GCCGAAAGGCGAGUGAGGUCU UUCCAGAU
3798





1303
GAAGCAUG G CGACUGGU
1496
ACCAGUCG GCCGAAAGGCGAGUGAGGUCU CAUGCUUC
3799





1310
GGCGACUG G UAACCGCC
1497
GGCGGUUA GCCGAAAGGCGAGUGAGGUCU CAGUCGCC
3800





1336
UGAAUCAA G CAGGCCAG
1498
CUGGCCUG GCCGAAAGGCGAGUGAGGUCU UUGAUUCA
3801





1340
UCAAGCAG G CCAGCUUU
1499
AAAGCUGG GCCGAAAGGCGAGUGAGGUCU CUGCUUGA
3802





1344
GCAGGCCA G CUUUUCCU
1500
AGGAAAAG GCCGAAAGGCGAGUGAGGUCU UGGCCUGC
3803





1363
UGCAGACAG UUGAGCUG
1501
CAGCUCAA GCCGAAAGGCGAGUGAGGUCU UGUCUGCA
3804





1368
ACAGUUGA G CUGGGGUC
1502
GACCCCAG GCCGAAAGGCGAGUGAGGUCU UCAACUGU
3805





1374
GAGCUGGG G UCCUGGGU
1503
ACCCAGGA GCCGAAAGGCGAGUGAGGUCU CCCAGCUC
3806





1381
GGUCCUGG G UUGGGAUG
1504
CAUCCCAA GCCGAAAGGCGAGUGAGGUCU CCAGGACC
3807





1390
UUGGGAUG G UGACAUUU
1505
AAAUGUCA GCCGAAAGGCGAGUGAGGUCU CAUCCCAA
3808





1403
AUUUGACA G UGCUGCCC
1506
GGGCAGCA GCCGAAAGGCGAGUGAGGUCU UGUCAAAU
3809





1421
UGUACAAA G UGAACUCA
1507
UGAGUUCA GCCGAAAGGCGAGUGAGGUCU UUUGUACA
3810





1442
GAUAAACA G UGGCAGUG
1508
CACUGCCA GCCGAAAGGCGAGUGAGGUCU UGUUUAUC
3811





1445
AAACAGUG G CAGUGACA
1509
UGUCACUG GCCGAAAGGCGAGUGAGGUCU CACUGUUU
3812





1448
CAGUGGCA G UGACAGGG
1510
CCCUGUCA GCCGAAAGGCGAGUGAGGUCU UGCCACUG
3813





1483
UACCUGCA G CAGCUUCA
1511
UGAAGCUG GCCGAAAGGCGAGUGAGGUCU UGCAGGUA
3814





1486
CUGCAGCA G CUUCAGGA
1512
UCCUGAAG GCCGAAAGGCGAGUGAGGUCU UGCUGCAG
3815





1500
GGAGGGAC G UCCAUCUG
1513
CAGAUGGA GCCGAAAGGCGAGUGAGGUCU GUCCCUCC
3816





1511
CAUCUGCA G CGGGCUUC
1514
GAAGCCCG GCCGAAAGGCGAGUGAGGUCU UGCAGAUG
3817





1515
UGCAGCGG G CUUCGAUC
1515
GAUCGAAG GCCGAAAGGCGAGUGAGGUCU CCGCUGCA
3818





1525
UUCGAUCG G CAUUUACU
1516
AGUAAAUG GCCGAAAGGCGAGUGAGGUCU CGAUCGAA
3819





1607
CACUAUAA G UGGGUGCU
1517
AGCACCCA GCCGAAAGGCGAGUGAGGUCU UUAUAGUG
3820





1611
AUAAGUGG G UGCUUUAA
1518
UUAAAGCA GCCGAAAGGCGAGUGAGGUCU CCACUUAU
3821





1624
UUAACGAG G UCAAACAA
1519
UUGUUUGA GCCGAAAGGCGAGUGAGGUCU CUCGUUAA
3822





1634
CAAACAAA G UGGUGCCA
1520
UGGCACCA GCCGAAAGGCGAGUGAGGUCU UUUGUUUG
3823





1637
ACAAAGUG G UGCCAUCA
1521
UGAUGGCA GCCGAAAGGCGAGUGAGGUCU CACUUUGU
3824





1654
UCCACACA G UCGCUUUG
1522
CAAAGCGA GCCGAAAGGCGAGUGAGGUCU UGUGUGGA
3825





1665
GCUUUGGG G CCCUCUGC
1523
GCAGAGGG GCCGAAAGGCGAGUGAGGUCU CCCAAAGC
3826





1675
CCUCUGCA G CUCAAGAA
1524
UUCUUGAG GCCGAAAGGCGAGUGAGGUCU UGCAGAGG
3827





1692
CUAGAGGA G CUGUCCAA
1525
UUGGACAG GCCGAAAGGCGAGUGAGGUCU UCCUCUAG
3828





1712
GACAGGAG G UUUACAGA
1526
UCUGUAAA GCCGAAAGGCGAGUGAGGUCU CUCCUGUC
3829





1738
CAGAUCAA G UUCAGAAC
1527
GUUCUGAA GCCGAAAGGCGAGUGAGGUCU UUGAUCUG
3830





1751
GAACAAUG G CCUCAUUG
1528
CAAUGAGG GCCGAAAGGCGAGUGAGGUCU CAUUGUUC
3831





1771
CUUUUGGG G CCCUUUCA
1529
UGAAAGGG GCCGAAAGGCGAGUGAGGUCU CCCAAAAG
3832





1792
GAAAUGGA G CUGUCUCU
1530
AGAGACAG GCCGAAAGGCGAGUGAGGUCU UCCAUUUC
3833





1803
GUCUCUCA G CGCUCCAU
1531
AUGGAGCG GCCGAAAGGCGAGUGAGGUCU UGAGAGAC
3834





1815
UCCAUCCA G CUUGAGAG
1532
CUCUCAAG GCCGAAAGGCGAGUGAGGUCU UGGAUGGA
3835





1823
GCUUGAGA G UAAGGGAU
1533
AUCCCUUA GCCGAAAGGCGAGUGAGGUCU UCUCAAGC
3836





1847
CCAGAACA G CCAGUGGA
1534
UCCACUGG GCCGAAAGGCGAGUGAGGUCU UGUUCUGG
3837





1851
AACAGCCA G UGGAUGAA
1535
UUCAUCCA GCCGAAAGGCGAGUGAGGUCU UGGCUGUU
3838





1862
GAUGAAUG G CACAGUGA
1536
UCACUGUG GCCGAAAGGCGAGUGAGGUCU CAUUCAUC
3839





1867
AUGGCACA G UGAUCGUG
1537
CACGAUCA GCCGAAAGGCGAGUGAGGUCU UGUGCCAU
3840





1873
CAGUGAUC G UGGACAGC
1538
GCUGUCCA GCCGAAAGGCGAGUGAGGUCU GAUCACUG
3841





1880
CGUGGACA G CACCGUGG
1539
CCACGGUG GCCGAAAGGCGAGUGAGGUCU UGUCCACG
3842





1885
ACAGCACC G UGGGAAAG
1540
CUUUCCCA GCCGAAAGGCGAGUGAGGUCU GGUGCUGU
3843





1926
ACAACGCA G CCUCCCCA
1541
UGGGGAGG GCCGAAAGGCGAGUGAGGUCU UGCGUUGU
3844





1955
GGAUCCCA G UGGACAGA
1542
UCUGUCCA GCCGAAAGGCGAGUGAGGUCU UGGGAUCC
3845





1965
GGACAGAA G CAAGGUGG
1543
CCACCUUG GCCGAAAGGCGAGUGAGGUCU UUCUGUCC
3846





1970
GAAGCAAG G UGGCUUUG
1544
CAAAGCCA GCCGAAAGGCGAGUGAGGUCU CUUGCUUC
3847





1973
GCAAGGUG G CUUUGUAG
1545
CUACAAAG GCCGAAAGGCGAGUGAGGUCU CACCUUGC
3848





1981
GCUUUGUA G UGGACAAA
1546
UUUGUCCA GCCGAAAGGCGAGUGAGGUCU UACAAAGC
3849





2002
CCAAAAUG G CCUACCUC
1547
GAGGUAGG GCCGAAAGGCGAGUGAGGUCU CAUUUUGG
3850





2021
AAUCCCAG G CAUUGCUA
1548
UAGCAAUG GCCGAAAGGCGAGUGAGGUCU CUGGGAUU
3851





2032
UUGCUAAG G UUGGCACU
1549
AGUGCCAA GCCGAAAGGCGAGUGAGGUCU CUUAGCAA
3852





2036
UAAGGUUG G CACUUGGA
1550
UCCAAGUG GCCGAAAGGCGAGUGAGGUCU CAACCUUA
3853





2051
GAAAUACA G UCUGCAAG
1551
CUUGCAGA GCCGAAAGGCGAGUGAGGUCU UGUAUUUC
3854





2059
GUCUGCAA G CAAGCUCA
1552
UGAGCUUG GCCGAAAGGCGAGUGAGGUCU UUGCAGAC
3855





2063
GCAAGCAA G CUCACAAA
1553
UUUGUGAG GCCGAAAGGCGAGUGAGGUCU UUGCUUGC
3856





2091
ACUGUCAC G UCCCGUGC
1554
GCACGGGA GCCGAAAGGCGAGUGAGGUCU GUGACAGU
3857





2096
CACGUCCC G UGCGUCCA
1555
UGGACGCA GCCGAAAGGCGAGUGAGGUCU GGGACGUG
3858





2100
UCCCGUGC G UCCAAUGC
1556
GCAUUGGA GCCGAAAGGCGAGUGAGGUCU GCACGGGA
3859





2128
CAAUUACA G UGACUUCC
1557
GGAAGUCA GCCGAAAGGCGAGUGAGGUCU UGUAAUUG
3860





2156
GGACACCA G CAAAUUCC
1558
GGAAUUUG GCCGAAAGGCGAGUGAGGUCU UGGUGUCC
3861





2168
AUUCCCCA G CCCUCUGG
1559
CCAGAGGG GCCGAAAGGCGAGUGAGGUCU UGGGGAAU
3862





2176
GCCCUCUG G UAGUUUAU
1560
AUAAACUA GCCGAAAGGCGAGUGAGGUCU CAGAGGGC
3863





2179
CUCUGGUA G UUUAUGCA
1561
UGCAUAAA GCCGAAAGGCGAGUGAGGUCU UACCAGAG
3864





2203
GCCAAGGA G CCUCCCCA
1562
UGGGGAGG GCCGAAAGGCGAGUGAGGUCU UCCUUGGC
3865





2221
UUCUCAGG G CCAGUGUC
1563
GACACUGG GCCGAAAGGCGAGUGAGGUCU CCUGAGAA
3866





2225
CAGGGCCA G UGUCACAG
1564
CUGUGACA GCCGAAAGGCGAGUGAGGUCU UGGCCCUG
3867





2233
GUGUCACA G CCCUGAUU
1565
AAUCAGGG GCCGAAAGGCGAGUGAGGUCU UGUGACAC
3868





2248
UUGAAUCA G UGAAUGGA
1566
UCCAUUCA GCCGAAAGGCGAGUGAGGUCU UGAUUCAA
3869





2263
GAAAAACA G UUACCUUG
1567
CAAGGUAA GCCGAAAGGCGAGUGAGGUCU UGUUUUUC
3870





2290
AUAAUGGA G CAGGUGCU
1568
AGCACCUG GCCGAAAGGCGAGUGAGGUCU UCCAUUAU
3871





2294
UGGAGCAG G UGCUGAUG
1569
CAUCAGCA GCCGAAAGGCGAGUGAGGUCU CUGCUCCA
3872





2318
GGAUGACG G UGUCUACU
1570
AGUAGACA GCCGAAAGGCGAGUGAGGUCU CGUCAUCC
3873





2331
UACUCAAG G UAUUUCAC
1571
GUGAAAUA GCCGAAAGGCGAGUGAGGUCU CUUGAGUA
3874





2357
CACGAAUG G UAGAUACA
1572
UGUAUCUA GCCGAAAGGCGAGUGAGGUCU CAUUCGUG
3875





2366
UAGAUACA G UGUAAAAG
1573
CUUUUACA GCCGAAAGGCGAGUGAGGUCU UGUAUCUA
3876





2374
GUGUAAAA G UGCGGGCU
1574
AGCCCGCA GCCGAAAGGCGAGUGAGGUCU UUUUACAC
3877





2380
AAGUGCGG G CUCUGGGA
1575
UCCCAGAG GCCGAAAGGCGAGUGAGGUCU CCGCACUU
3878





2392
UGGGAGGA G UUAACGCA
1576
UGCGUUAA GCCGAAAGGCGAGUGAGGUCU UCCUCCCA
3879





2401
UUAACGCA G CCAGACGG
1577
CCGUCUGG GCCGAAAGGCGAGUGAGGUCU UGCGUUAA
3880





2413
GACGGAGA G UGAUACCC
1578
GGGUAUCA GCCGAAAGGCGAGUGAGGUCU UCUCCGUC
3881





2424
AUACCCCA G CAGAGUGG
1579
CCACUCUG GCCGAAAGGCGAGUGAGGUCU UGGGGUAU
3882





2429
CCAGCAGA G UGGAGCAC
1580
GUGCUCCA GCCGAAAGGCGAGUGAGGUCU UCUGCUGG
3883





2434
AGAGUGGA G CACUGUAC
1581
GUACAGUG GCCGAAAGGCGAGUGAGGUCU UCCACUCU
3884





2450
CAUACCUG G CUGGAUUG
1582
CAAUCCAG GCCGAAAGGCGAGUGAGGUCU CAGGUAUG
3885





2523
CAACACAA G CAAGUGUG
1583
CACACUUG GCCGAAAGGCGAGUGAGGUCU UUGUGUUG
3886





2527
ACAAGCAA G UGUGUUEU
1584
GAAACACA GCCGAAAGGCGAGUGAGGUCU UUGCUUGU
3887





2537
GUGUUUCA G CAGAACAU
1585
AUGUUCUG GCCGAAAGGCGAGUGAGGUCU UGAAACAC
3888





2555
CUCGGGAG G CUCAUUUG
1586
CAAAUGAG GCCGAAAGGCGAGUGAGGUCU CUCCCGAG
3889





2566
CAUUUGUG G CUUCUGAU
1587
AUCAGAAG GCCGAAAGGCGAGUGAGGUCU CACAAAUG
3890





2612
CCCACCUG G CCAAAUCA
1588
UGAUUUGG GCCGAAAGGCGAGUGAGGUCU CAGGUGGG
3891





2632
ACCUGAAG G CGGAAAUU
1589
AAUUUCCG GCCGAAAGGCGAGUGAGGUCU CUUCAGGU
3892





2648
UCACGGGG G CAGUCUCA
1590
UGAGACUG GCCGAAAGGCGAGUGAGGUCU CCCCGUGA
3893





2651
CGGGGGCA G UCUCAUUA
1591
UAAUGAGA GCCGAAAGGCGAGUGAGGUCU UGCCCCCG
3894





2674
CUUGGACA G CUCCUGGG
1592
CCCAGGAG GCCGAAAGGCGAGUGAGGUCU UGUCCAAG
3895





2704
AUGGAACA G CUCACAAG
1593
CUUGUGAG GCCGAAAGGCGAGUGAGGUCU UGUUCCAU
3896





2712
GCUCACAA G UAUAUCAU
1594
AUGAUAUA GCCGAAAGGCGAGUGAGGUCU UUGUGAGC
3897





2729
UCGAAUAA G UACAAGUA
1595
UACUUGUA GCCGAAAGGCGAGUGAGGUCU UUAUUCGA
3898





2735
AAGUACAA G UAUUCUUG
1596
CAAGAAUA GCCGAAAGGCGAGUGAGGUCU UUGUACUU
3899





2757
AGAGACAA G UUCAAUGA
1597
UCAUUGAA GCCGAAAGGCGAGUGAGGUCU UUGUCUCU
3900





2776
CUCUUCAA G UGAAUACU
1598
AGUAUUCA GCCGAAAGGCGAGUGAGGUCU UUGAAGAG
3901





2806
CAAAGGAA G CCAACUCU
1599
AGAGUUGG GCCGAAAGGCGAGUGAGGUCU UUCCUUUG
3902





2821
CUGAGGAA G UCUUUUUG
1600
CAAAAAGA GCCGAAAGGCGAGUGAGGUCU UUCCUCAG
3903





2861
UGAAAAUG G CACAGAUC
1601
GAUCUGUG GCCGAAAGGCGAGUGAGGUCU CAUUUUCA
3904





2887
CUAUUCAG G CUGUUGAU
1602
AUCAACAG GCCGAAAGGCGAGUGAGGUCU CUGAAUAG
3905





2899
UUGAUAAG G UCGAUCUG
1603
CAGAUCGA GCCGAAAGGCGAGUGAGGUCU CUUAUCAA
3906





2935
UUGCACGA G UAUCUUUG
1604
CAAAGAUA GCCGAAAGGCGAGUGAGGUCU UCGUGCAA
3907





2978
GACACCUA G UCCUGAUG
1605
CAUCAGGA GCCGAAAGGCGAGUGAGGUCU UAGGUGUC
3908





2991
GAUGAAAC G UCUGCUCC
1606
GGAGCAGA GCCGAAAGGCGAGUGAGGUCU GUUUCAUC
3909





3023
UAUCAACA G CACCAUUC
1607
GAAUGGUG GCCGAAAGGCGAGUGAGGUCU UGUUGAUA
3910





3035
CAUUCCUG G CAUUCACA
1068
UGUGAAUG GCCGGAAAGGCGAGUGAGGUCU CAGGAAUG
3911





3063
AUGUGGAA G UGGAUAGG
1609
CCUAUCCA GCCGAAAGGCGGAGUGAGGUCU UUCCACAU
3912





3081
GAACUGCA G CUGUCAAU
1610
AUUGACAG GCCGAAAGGCGAGUGAGGUCU UGCAGUUC
3913





3091
UGUCAAUA G CCUAGGGC
1611
GCCCUAGG GCCGAAAGGCGAGUGAGGUCU UAUUGACA
3914





3098
AGCCUAGG G CUGAAUUU
1612
AAAUUCAG GCCGAAAGGCGAGUGAGGUCU CCUAGGCU
3915





3189
UGUAGGGG G CGAUAUAC
1613
GUAAUCG GCCGAAAGGCGAGUGAGGUCU CCCCUACA
3916





3242
UGUAGGGG G CGAUAUAC
1613
GUAUAUCG GCCGAAAGGCGAGUGAGGUCU CCCCUACA
3916





3210
UGUAUAUA G UACAUUUA
1614
UAAAUGUA GCCGAAAGGCGAGUGAGGUCU UAUAUACA
3917





3279
UGUAGGGG G CGAUAAAA
1615
UUUUAUCG GCCGAAAGGCGAGUGAGGUCU CCCCUACA
3918






Input Sequence = NM_001285. Cut Site = G/Y




Arm Length = 8. Core Sequence = GCcgaaagGCGaGuCaaGGuCu




NM_001285 (Homo sapiens chloride channel, calcium activated, 1 (CLCA1) mRNA, 3311bp)








[0194]

7





TABLE VII










Human CLCA1 DNAzyme and Target Sequence 249.021













Seq

Rz




ID

Seq ID


Pos
Substrate
No
Dnazyme
No














17
CUUUUGGU A CAAAUGGA
4
TCCATTTG GGCTAGCTACAACGA ACCAAAAG
3919





34
UGUGGAAU A UAAUUGAA
5
TTCAATTA GGCTAGCTACAACGA ATTCCACA
3920





44
AAUUGAAU A UUUUCUUG
8
CAAGAAAA GGCTAGCTACAACGA ATTCAATT
3921





84
UUGAGGUU A UGUCAAGC
19
GCTTGACA GGCTAGCTACAACGA AACCTCAA
3922





122
AUGGAAAU A UUUACAAG
22
CTTGTAAA GGCTAGCTACAACGA ATTTCCAT
3923





126
AAAUAUUU A CAAGUACG
25
CGTACTTG GGCTAGCTACAACGA AAATATTT
3924





132
UUACAAGU A CGCAAUUU
26
AAATTGCG GGCTAGCTACAACGA ACTTGTAA
3925





152
ACUAAGAU A UUGUUAUC
30
GATAACAA GGCTAGCTACAACGA ATCTTAGT
3926





158
AUAUUGUU A UCAUUCUC
33
GAGAATGA GGCTAGCTACAACGA AACAATAT
3927





169
AUUCUCCU A UUGAAGAC
38
GTCTTCAA GGCTAGCTACAACGA AGGAGAAT
3928





259
GUGUGUCU A UAUUUUCA
52
TGAAAATA GGCTAGCTACAACGA AGACACAC
3929





261
GUGUCUAU A UUUUCAUA
53
TATGAAAA GGCTAGCTACAACGA ATAGACAC
3930





269
AUUUUCAU A UCUGUAUA
58
TATACAGA GGCTAGCTACAACGA ATGAAAAT
3931





275
AUAUCUGU A UAUAUAUA
60
TATATATA GGCTAGCTACAACGA ACAGATAT
3932





277
AUCUGUAU A UAUAUAAU
61
ATTATATA GGCTAGCTACAACGA ATACAGAT
3933





279
CUGUAUAU A UAUAAUGG
62
CCATTATA GGCTAGCTACAACGA ATATACAG
3934





281
GUAUAUAU A UAAUGGUA
63
TACCATTA GGCTAGCTACAACGA ATATATAC
3935





346
GGAGAUGU A CAGCAAUG
74
CATTGCTG GGCTAGCTACAACGA ACATCTCC
3936





446
CAAUGGCU A UGAAGGCA
97
TGCCTTCA GGCTAGCTACAACGA AGCCATTG
3937





539
AUCUCUGU A UCUGUUUG
108
CAAACAGA GGCTAGCTACAACGA ACAGAGAT
3938





553
UUGAAGCU A CAGGAAAG
112
CTTTCCTG GGCTAGCTACAACGA AGCTTCAA
3939





569
GCGAUUUU A UUUCAAAA
116
TTTTGAAA GGCTAGCTACAACGA AAAATCGC
3940





623
GGCUGACU A UGUGAGAC
126
GTCTCACA GGCTAGCTACAACGA AGTCAGCC
3941





647
UGAGACCU A CAAAAAUG
128
CATTTTTG GGCTAGCTACAACGA AGGTCTCA
3942





679
CUGAGUCU A CUCCUCCA
133
TGGAGGAG GGCTAGCTACAACGA AGACTCAG
3943





704
UGAACCCU A CACUGAGC
137
GCTCAGTG GGCTAGCTACAACGA AGGGTTCA
3944





791
AGCUGAAU A UGGACCAC
147
GTGGTCCA GGCTAGCTACAACGA ATTCAGCT
3945





834
GCUCAUCU A CGAUGGGG
154
CCCCATCG GGCTAGCTACAACGA AGATGAGC
3946





846
UGGGGAGU A UUUGACGA
155
TCGTCAAA GGCTAGCTACAACGA ACTCCCCA
3947





857
UGACGAGU A CAAUAAUG
158
CATTATTG GGCTAGCTACAACGA ACTCGTCA
3948





878
GAAAUUCU A CUUAUCCA
162
TGGATAAG GGCTAGCTACAACGA AGAATTTC
3949





882
UUCUACUU A UCCAAUGG
164
CCATTGGA GGCTAGCTACAACGA AAGTAGAA
3950





897
GGAAGAAU A CAAGCAGU
166
ACTGCTTG GGCTAGCTACAACGA ATTCTTCC
3951





922
CAGCAGGU A UUACUGGU
170
ACCAGTAA GGCTAGCTACAACGA ACCTGCTG
3952





925
CAGGUAUU A CUGGUACA
172
TGTACCAG GGCTAGCTACAACGA AATACCTG
3953





931
UUACUGGU A CAAAUGUA
173
TACATTTG GGCTAGCTACAACGA ACCAGTAA
3954





968
CAGCUGUU A CACCAAAA
178
TTTTGGTG GGCTAGCTACAACGA AACAGCTG
3955





997
AUAAAGUU A CAGGACUC
183
GAGTCCTG GGCTAGCTACAACGA AACTTTAT
3956





1007
AGGACUCU A UGAAAAAG
185
CTTTTTCA GGCTAGCTACAACGA AGAGTCCT
3957





1060
AGGCUUCU A UAAUGUUU
194
AAACATTA GGCTAGCTACAACGA AGAAGCCT
3958





1087
UUGAUUCU A UAGUUGAA
201
TTCAACTA GGCTAGCTACAACGA AGAATCAA
3959





1102
AAUUCUGU A CAGAACAA
206
TTGTTCTG GGCTAGCTACAACGA ACAGAATT
3960





1213
CCACUCCU A UGACAACA
218
TGTTGTCA GGCTAGCTACAACGA AGGAGTGG
3961





1416
GCCCAUGU A CAAAGUGA
245
TCACTTTG GGCTAGCTACAACGA ACATGGGC
3962





1431
GAACUCAU A CAGAUAAA
247
TTTATCTG GGCTAGCTACAACGA ATGAGTTC
3963





1476
AAAAGAUU A CCUGCAGC
251
GCTGCAGG GGCTAGCTACAACGA AATCTTTT
3964





1531
CGGCAUUU A CUGUGAUU
261
AATCACAG GGCTAGCTACAACGA AAATGCCG
3965





1550
GAAGAAAU A UCCAACUG
264
CAGTTGGA GGCTAGCTACAACGA ATTTCTTC
3966





1603
ACAACACU A UAAGUGGG
268
CCCACTTA GGCTAGCTACAACGA AGTGTTGT
3967





1716
GGAGGUUU A CAGACAUA
285
TATGTCTG GGCTAGCTACAACGA AAACCTCC
3968





1724
ACAGACAU A UGCUUCAG
286
CTGAAGCA GGCTAGCTACAACGA ATGTCTGT
3969





1909
UGUUUCUU A UCACCUGG
318
CCAGGTGA GGCTAGCTACAACGA AAGAAACA
3970





2006
AAUGGCCU A CCUCCAAA
329
TTTGGAGG GGCTAGCTACAACGA AGGCCATT
3971





2048
UUGGAAAU A CAGUCUGC
336
GCAGACTG GGCTAGCTACAACGA ATTTCCAA
3972





2110
CCAAUGCU A CCCUGCCU
343
AGGCAGGG GGCTAGCTACAACGA AGCATTGG
3973





2125
CUCCAAUU A CAGUGACU
346
AGTCACTG GGCTAGCTACAACGA AATTGGAG
3974





2183
GGUAGUUU A UGCAAAUA
355
TATTTGCA GGCTAGCTACAACGA AAACTACC
3975





2191
AUGCAAAU A UUCGCCAA
356
TTGGCGAA GGCTAGCTACAACGA ATTTGCAT
3976





2266
AAACAGUU A CCUUGGAA
367
TTCCAAGG GGCTAGCTACAACGA AACTGTTT
3977





2277
UUGGAACU A CUGGAUAA
369
TTATCCAG GGCTAGCTACAACGA AGTTCCAA
3978





2305
CUGAUGCU A CUAAGGAU
371
ATCCTTAG GGCTAGCTACAACGA AGCATCAG
3979





2324
CGGUGUCU A CUCAAGGU
374
ACCTTGAG GGCTAGCTACAACGA AGACACCG
3980





2333
CUCAAGGU A UUUCACAA
376
TTGTGAAA GGCTAGCTACAACGA ACCTTGAG
3981





2345
CACAACUU A UGACACGA
381
TCGTGTCA GGCTAGCTACAACGA AAGTTGTG
3982





2363
UGGUAGAU A CAGUGUAA
383
TTACACTG GGCTAGCTACAACGA ATCTACCA
3983





2418
AGAGUGAU A CCCCAGCA
388
TGCTGGGG GGCTAGCTACAACGA ATCACTCT
3984





2441
AGCACUGU A CAUACCUG
389
CAGGTATG GGCTAGCTACAACGA ACAGTGCT
3985





2445
CUGUACAU A CCUGGCUG
390
CAGCCAGG GGCTAGCTACAACGA ATGTACAG
3986





2472
GAUGAAAU A CAAUGGAA
392
TTCCATTG GGCTAGCTACAACGA ATTTCATC
3987





2592
GCUCCCAU A CCUGAUCU
411
AGATCAGG GGCTAGCTACAACGA ATGGGAGC
3988





2690
GGAUGAUU A UGACCAUG
427
CATGGTCA GGCTAGCTACAACGA AATCATCC
3989





2714
UCACAAGU A UAUCAUUC
429
GAATGATA GGCTAGCTACAACGA ACTTGTGA
3990





2716
ACAAGUAU A UCAUUCGA
430
TCGAATGA GGCTAGCTACAACGA ATACTTGT
3991





2731
GAAUAAGU A CAAGUAUU
435
AATACTTG GGCTAGCTACAACGA ACTTATTC
3992





2737
GUACAAGU A UUCUUGAU
436
ATCAAGAA GGCTAGCTACAACGA ACTTGTAC
3993





2782
AAGUGAAU A CUACUGCU
448
AGCAGTAG GGCTAGCTACAACGA ATTCACTT
3994





2785
UGAAUACU A CUGCUCUC
449
GAGAGCAG GGCTAGCTACAACGA AGTATTCA
3995





2848
AAAACAUU A CUUUUGAA
463
TTCAAAAG GGCTAGCTACAACGA AATGTTTT
3996





2881
UCAUUGCU A UUCAGGCU
473
AGCCTGAA GGCTAGCTACAACGA AGCAATGA
3997





2919
UCAGAAAU A UCCAACAU
481
ATGTTGGA GGCTAGCTACAACGA ATTTCTGA
3998





2937
GCACGAGU A UCUUUGUU
484
AACAAAGA GGCTAGCTACAACGA ACTCGTGC
3999





2947
CUUUGUUU A UUCCUCCA
490
TGGAGGAA GGCTAGCTACAACGA AAACAAAG
4000





3010
GUCCUAAU A UUCAUAUC
502
GATATGAA GGCTAGCTACAACGA ATTAGGAC
4001





3016
AUAUUCAU A UCAACAGC
505
GCTGTTGA GGCTAGCTACAACGA ATGAATAT
4002





3055
UAAAAAUU A UGUGGAAG
516
CTTCCACA GGCTAGCTACAACGA AATTTTTA
4003





3149
UUUUGAUU A UAAAAUUU
540
AAATTTTA GGCTAGCTACAACGA AATCAAAA
4004





3168
UAAAAUGU A UUUUAGAC
547
GTCTAAAA GGCTAGCTACAACGA ACATTTTA
4005





3194
GGGGCGAU A UACUAAAU
555
ATTTAGTA GGCTAGCTACAACGA ATCGCCCC
4006





3247
GGGGCGAU A UACUAAAU
555
ATTTAGTA GGCTAGCTACAACGA ATCGCCCC
4006





3196
GGCGAUAU A CUAAAUGU
556
ACATTTAG GGCTAGCTACAACGA ATATCGCC
4007





3249
GGCGAUAU A CUAAAUGU
556
ACATTTAG GGCTAGCTACAACGA ATATCGCC
4007





3205
CUAAAUGU A UAUAGUAC
558
GTACTATA GGCTAGCTACAACGA ACATTTAG
4008





3207
AAAUGUAU A UAGUACAU
559
ATGTACTA GGCTAGCTACAACGA ATACATTT
4009





3212
UAUAUAGU A CAUUUAUA
561
TATAAATG GGCTAGCTACAACGA ACTATATA
4010





3218
GUACAUUU A UACUAAAU
564
ATTTAGTA GGCTAGCTACAACGA AAATGTAC
4011





3220
ACAUUUAU A CUAAAUGU
565
ACATTTAG GGCTAGCTACAACGA ATAAATGT
4012





3229
CUAAAUGU A UUCCUGUA
567
TACAGGAA GGCTAGCTACAACGA ACATTTAG
4013





3258
CUAAAUGU A UUUUAGAC
572
GTCTAAAA GGCTAGCTACAACGA ACATTTAG
4014





65
AGGGGAGC A UGAAGAGG
579
CCTCTTCA GGCTAGCTACAACGA GCTCCCCT
4015





93
UGUCAAGC A UCUGGCAC
581
GTGCCAGA GGCTAGCTACAACGA GCTTGACA
4016





100
CAUCUGGC A CAGCUGAA
583
TTCAGCTG GGCTAGCTACAACGA GCCAGATG
4017





161
UUGUUAUC A UUCUCCUA
590
TAGGAGAA GGCTAGCTACAACGA GATAACAA
4018





195
AGUAAAAC A CAUCAGGU
596
ACCTGATG GGCTAGCTACAACGA GTTTTACT
4019





197
UAAAACAC A UCAGGUCA
597
TGACCTGA GGCTAGCTACAACGA GTGTTTTA
4020





231
GAUAAACC A CUUCCGAU
603
ATCGGAAG GGCTAGCTACAACGA GGTTTATC
4021





267
AUAUUUUC A UAUCUGUA
607
TACAGATA GGCTAGCTACAACGA GAAAATAT
4022





299
AGAAAGAC A CCUUCGUA
609
TACGAAGG GGCTAGCTACAACGA GTCTTTCT
4023





314
UAACCCGC A UUUUCCAA
614
TTGGAAAA GGCTAGCTACAACGA GCGGGTTA
4024





334
GAGGAAUC A CAGGGAGA
617
TCTCCCTG GGCTAGCTACAACGA GATTCCTC
4025





360
AUGGGGCC A UUUAAGAG
622
CTCTTAAA GGCTAGCTACAACGA GGCCCCAT
4026





379
CUGUGUUC A UCUUGAUU
624
AATCAAGA GGCTAGCTACAACGA GAACACAG
4027





392
GAUUCUUC A CCUUCUAG
627
CTAGAAGG GGCTAGCTACAACGA GAAGAATC
4028





420
AGUAAUUC A CUCAUUCA
634
TGAATGAG GGCTAGCTACAACGA GAATTACT
4029





424
AUUCACUC A UUCAGCUG
636
CAGCTGAA GGCTAGCTACAACGA GAGTGAAT
4030





454
AUGAAGGC A UUGUCGUU
642
AACGACAA GGCTAGCTACAACGA GCCTTCAT
4031





495
GAUGAAAC A CUCAUUCA
650
TGAATGAG GGCTAGCTACAACGA GTTTCATC
4032





499
AAACACUC A UUCAACAA
652
TTGTTGAA GGCTAGCTACAACGA GAGTGTTT
4033





517
UAAAGGAC A UGGUGACC
655
GGTCACCA GGCTAGCTACAACGA GTCCTTTA
4034





531
ACCCAGGC A UCUCUGUA
659
TACAGAGA GGCTAGCTACAACGA GCCTGGGT
4035





586
AUGUUGCC A UUUUGAUU
667
AATCAAAA GGCTAGCTACAACGA GGCAACAT
4036





603
CCUGAAAC A UGGAAGAC
670
GTCTTCCA GGCTAGCTACAACGA GTTTCAGG
4037





706
AACCCUAC A CUGAGCAG
692
CTGCTCAG GGCTAGCTACAACGA GTAGGGTT
4038





749
AAGGAUCC A CCUCACUC
698
GAGTGAGG GGCTAGCTACAACGA GGATCCTT
4039





754
UCCACCUC A CUCCUGAU
701
ATCAGGAG GGCTAGCTACAACGA GAGGTGGA
4040





766
CUGAUUUC A UUGCAGGA
705
TCCTGCAA GGCTAGCTACAACGA GAAATCAG
4041





798
UAUGGACC A CAAGGUAA
709
TTACCTTG GGCTAGCTACAACGA GGTCCATA
4042





810
GGUAAGGC A UUUGUCCA
711
TGGACAAA GGCTAGCTACAACGA GCCTTACC
4043





818
AUUUGUCC A UGAGUGGG
713
CCCACTCA GGCTAGCTACAACGA GGACAAAT
4044





830
GUGCGCUC A UCUACGAU
715
ATCGTAGA GGCTAGCTACAACGA GAGCCCAC
4045





970
GCUGUUAC A CCAAAAGA
731
TCTTTTGG GGCTAGCTACAACGA GTAACAGC
4046





982
AAAGAUGC A CAUUCAAU
734
ATTGAATG GGCTAGCTACAACGA GCATCTTT
4047





984
AGAUGCAC A UUCAAUAA
735
TTATTGAA GGCTAGCTACAACGA GTGCATCT
4048





1071
AUGUUUGC A CAACAUGU
749
ACATGTTG GGCTAGCTACAACGA GCAAACAT
4049





1076
UGCACAAC A UGUUGAUU
751
AATCAACA GGCTAGCTACAACGA GTTGTGCA
4050





1115
ACAAAACC A CAACAAAG
757
CTTTGTTG GGCTAGCTACAACGA GGTTTTGT
4051





1165
UCCGAAGC A CAUGGGAA
769
TTCCCATG GGCTAGCTACAACGA GCTTCGGA
4052





1167
CGAAGCAC A UGGGAAGU
770
ACTTCCCA GGCTAGCTACAACGA GTGCTTCG
4053





1207
AGAAAACC A CUCCUAUG
775
CATAGGAG GGCTAGCTACAACGA GGTTTTCT
4054





1221
AUGACAAC A CAGCCACC
780
GGTGGCTG GGCTAGCTACAACGA GTTGTCAT
4055





1227
ACACAGCC A CCAAAUCC
783
GGATTTGG GGCTAGCTACAACGA GGCTGTGT
4056





1237
CAAAUCCC A CCUUCUCA
788
TGAGAAGG GGCTAGCTACAACGA GGGATTTG
4057





1245
ACCUUCUC A UUGCUGCA
792
TGCAGCAA GGCTAGCTACAACGA GAGAAGGT
4058





1300
CUGGAAGC A UGGCGACU
800
AGTCGCCA GGCTAGCTACAACGA GCTTCCAG
4059





1395
AUGGUGAC A UUUGACAG
820
CTGTCAAA GGCTAGCTACAACGA GTCACCAT
4060





1412
UGCUGCCC A UGUACAAA
825
TTTGTACA GGCTAGCTACAACGA GGGCAGCA
4061





1429
GUGAACUC A UACAGAUA
828
TATCTGTA GGCTAGCTACAACGA GAGTTCAC
4062





1459
ACAGGGAC A CACUCGCC
833
GGCGAGTG GGCTAGCTACAACGA GTCCCTGT
4063





1461
AGGGACAC A CUCGCCAA
834
TTGGCGAG GGCTAGCTACAACGA GTGTCCCT
4064





1504
GGACGUCC A UCUGCAGC
845
GCTGCAGA GGCTAGCTACAACGA GGACGTCC
4065





1527
CGAUCGGC A UUUACUGU
849
ACAGTAAA GGCTAGCTACAACGA GCCGATCG
4066





1600
AAGACAAC A CUAUAAGU
858
ACTTATAG GGCTAGCTACAACGA GTTGTCTT
4067





1642
GUGGUGCC A UCAUCCAC
864
GTGGATGA GGCTAGCTACAACGA GGCACCAC
4068





1645
GUGCCAUC A UCCACACA
865
TGTGTGGA GGCTAGCTACAACGA GATGGCAC
4069





1649
CAUCAUCC A CACAGUCG
867
CGACTGTG GGCTAGCTACAACGA GGATGATG
4070





1651
UCAUCCAC A CAGUCGCU
868
AGCGACTG GGCTAGCTACAACGA GTGGATGA
4071





1722
UUACAGAC A UAUGCUUC
884
GAAGCATA GGCTAGCTACAACGA GTCTGTAA
4072





1756
AUGGCCUC A UUGAUGCU
892
AGCATCAA GGCTAGCTACAACGA GAGGCCAT
4073





1779
GCCCUUUC A UCAGGAAA
897
TTTCCTGA GGCTAGCTACAACGA GAAAGGGC
4074





1810
AGCGCUCC A UCCAGCUU
905
AAGCTGGA GGCTAGCTACAACGA GGAGCGCT
4075





1864
UGAAUGGC A CAGUGAUC
917
GATCACTG GGCTAGCTACAACGA GCCATTCA
4076





1882
UGGACAGC A CCGUGGGA
920
TCCCACGG GGCTAGCTACAACGA GCTGTCCA
4077





1897
GAAAGGAC A CUUUGUUU
922
AAACAAAG GGCTAGCTACAACGA GTCCTTTC
4078





1912
UUCUUAUC A CCUGGACA
925
TGTCCAGG GGCTAGCTACAACGA GATAAGAA
4079





1993
ACAAAAAC A CCAAAAUG
947
CATTTTGG GGCTAGCTACAACGA GTTTTTGT
4080





2023
UCCCAGGC A UUGCUAAG
959
CTTAGCAA GGCTAGCTACAACGA GCCTGGGA
4081





2038
AGGUUGGC A CUUGGAAA
961
TTTCCAAG GGCTAGCTACAACGA GCCAACCT
4082





2067
GCAAGCUC A CAAACCUU
968
AAGGTTTG GGCTAGCTACAACGA GAGCTTGC
4083





2089
UGACUGUC A CGUCCCGU
976
ACGGGACG GGCTAGCTACAACGA GACAGTCA
4084





2152
ACAAGGAC A CCAGCAAA
994
TTTGCTGG GGCTAGCTACAACGA GTCCTTGT
4085





2230
CCAGUGUC A CAGCCCUG
1019
CAGGGCTG GGCTAGCTACAACGA GACACTGG
4086





2338
GGUAUUUC A CAACUUAU
1037
ATAAGTTG GGCTAGCTACAACGA GAAATACC
4087





2350
CUUAUGAC A CGAAUGGU
1040
ACCATTCG GGCTAGCTACAACGA GTCATAAG
4088





2436
AGUGGAGC A CUGUACAU
1052
ATGTACAG GGCTAGCTACAACGA GCTCCACT
4089





2443
CACUGUAC A UACCUGGC
1054
GCCAGGTA GGCTAGCTACAACGA GTACAGTG
4090





2484
UGGAAUCC A CCAAGACC
1060
GGTCTTGG GGCTAGCTACAACGA GGATTCCA
4091





2519
UGUUCAAC A CAAGCAAG
1066
CTTGCTTG GGCTAGCTACAACGA GTTGAACA
4092





2544
AGCAGAAC A UCCUCGGG
1071
CCCGAGGA GGCTAGCTACAACGA GTTCTGCT
4093





2559
GGAGGCUC A UUUGUGGC
1075
GCCACAAA GGCTAGCTACAACGA GAGCCTCC
4094





2590
AUGCUCCC A UACCUGAU
1084
ATCAGGTA GGCTAGCTACAACGA GGGAGCAT
4095





2607
CUCUUCCC A CCUGGCCA
1091
TGGCCAGG GGCTAGCTACAACGA GGGAAGAG
4096





2620
GCCAAAUC A CCGACCUG
1096
CAGGTCGG GGCTAGCTACAACGA GATTTGGC
4097





2642
GGAAAUUC A CGGGGGCA
1100
TGCCCCCG GGCTAGCTACAACGA GAATTTCC
4098





2656
GCAGUCUC A UUAAUCUG
1103
CAGATTAA GGCTAGCTACAACGA GAGACTGC
4099





2696
UUAUGACC A UGGAACAG
1111
CTGTTCCA GGCTAGCTACAACGA GGTCATAA
4100





2708
AACAGCUC A CAAGUAUA
1114
TATACTTG GGCTAGCTACAACGA GAGCTGTT
4101





2719
AGUAUAUC A UUCGAAUA
1116
TATTCGAA GGCTAGCTACAACGA GATATACT
4102





2794
CUGCUCUC A UCCCAAAG
1130
CTTTGGGA GGCTAGCTACAACGA GAGAGCAG
4103





2845
CAGAAAAC A UUACUUUU
1141
AAAAGTAA GGCTAGCTACAACGA GTTTTCTG
4104





2863
AAAAUGGC A CAGAUCUU
1143
AAGATCTG GGCTAGCTACAACGA GCCATTTT
4105





2875
AUCUUUUC A UUGCUAUU
1146
AATAGCAA GGCTAGCTACAACGA GAAAAGAT
4106





2926
UAUCCAAC A UUGCACCA
1154
TCGTGCAA GGCTAGCTACAACGA GTTGGATA
4107





2931
AACAUUGC A CGAGUAUC
1155
GATACTCG GGCTAGCTACAACGA GCAATGTT
4108





2955
AUUCCUCC A CAGACUCC
1160
GGAGTCTG GGCTAGCTACAACGA GGAGGAAT
4109





2973
CCAGAGAC A CCUAGUCC
1166
GGACTAGG GGCTAGCTACAACGA GTCTCTGG
4110





3014
UAAUAUUC A UAUCAACA
1177
TGTTGATA GGCTAGCTACAACGA GAATATTA
4111





3025
UCAACAGC A CCAUUCCU
1180
AGGAATGG GGCTAGCTACAACGA GCTGTTGA
4112





3028
ACAGCACC A UUCCUGGC
1182
GCCAGGAA GGCTAGCTACAACGA GGTGCTGT
4113





3037
UUCCUGGC A UUCACAUU
1185
AATGTGAA GGCTAGCTACAACGA GCCAGGAA
4114





3041
UGGCAUUC A CAUUUUAA
1186
TTAAAATG GGCTAGCTACAACGA GAATGCCA
4115





3043
GCAUUCAC A UUUUAAAA
1187
TTTTAAAA GGCTAGCTACAACGA GTGAATGC
4116





3130
AAUAAAUC A UUCAUCCU
1196
AGGATGAA GGCTAGCTACAACGA GATTTATT
4117





3134
AAUCAUUC A UCCUUUUU
1197
AAAAAGGA GGCTAGCTACAACGA GAATGATT
4118





3214
UAUAGUAC A UUUAUACU
1205
AGTATAAA GGCTAGCTACAACGA GTACTATA
4119





134
ACAAGUAC G CAAUUUGA
1215
TCAAATTG GGCTAGCTACAACGA GTACTTGT
4120





312
CGUAACCC G CAUUUUCC
1220
GGAAAATG GGCTAGCTACAACGA GGGTTACG
4121





463
UUGUCGUU G CAAUCGAC
1225
GTCGATTG GGCTAGCTACAACGA AACGACAA
4122





480
CCCAAUGU G CCAGAAGA
1227
TCTTCTGG GGCTAGCTACAACGA ACATTGGG
4123





583
AAAAUGUU G CCAUUUUG
1232
CAAAATGG GGCTAGCTACAACGA AACATTTT
4124





655
ACAAAAAU G CUGAUGUU
1238
AACATCAG GGCTAGCTACAACGA ATTTTTGT
4125





670
UUCUGGUU G CUGAGUCU
1240
AGACTCAG GGCTAGCTACAACGA AACCAGAA
4126





769
AUUUCAUU G CAGGAAAA
1247
TTTTCCTG GGCTAGCTACAACGA AATGAAAT
4127





980
CAAAAGAU G CACAUUCA
1255
TGAATGTG GGCTAGCTACAACGA ATCTTTTG
4128





1040
CCAAUCCC G CCAGACGG
1258
CCGTCTGG GGCTAGCTACAACGA GGGATTGG
4129





1069
UAAUGUUU G CACAACAU
1259
ATGTTGTG GGCTAGCTACAACGA AAACATTA
4130





1151
UCAAAAAU G CAAUCUCC
1262
GGAGATTG GGCTAGCTACAACGA ATTTTTGA
4131





1248
UUCUCAUU G CUGCAGAU
1268
ATCTGCAG GGCTAGCTACAACGA AATGAGAA
4132





1251
UCAUUGCU G CAGAUUGG
1269
CCAATCTG GGCTAGCTACAACGA AGCAATGA
4133





1316
UGGUAACC G CCUCAAUC
1272
GATTGAGG GGCTAGCTACAACGA GGTTACCA
4134





1353
CUUUUCCU G CUGCAGAC
1275
GTCTGCAG GGCTAGCTACAACGA AGGAAAAG
4135





1356
UUCCUGCU G CAGACAGU
1276
ACTGTCTG GGCTAGCTACAACGA AGCAGGAA
4136





1405
UUGACAGU G CUGCCCAU
1280
ATGGGCAG GGCTAGCTACAACGA ACTGTCAA
4137





1408
ACAGUGCU G CCCAUGUA
1281
TACATGGG GGCTAGCTACAACGA AGCACTGT
4138





1465
ACACACUC G CCAAAAGA
1284
TCTTTTGG GGCTAGCTACAACGA GAGTGTGT
4139





1480
GAUUACCU G CAGCAGCU
1285
AGCTGCTG GGCTAGCTACAACGA AGGTAATC
4140





1508
GUCCAUCU G CAGCGGGC
1286
GCCCGCTG GGCTAGCTACAACGA AGATGGAC
4141





1575
GAAAUUGU G CUGCUGAC
1291
GTCAGCAG GGCTAGCTACAACGA ACAATTTC
4142





1578
AUUGUGCU G CUGACGGA
1292
TCCGTCAG GGCTAGCTACAACGA AGCACAAT
4143





1613
AAGUGGGU G CUUUAACG
1294
CGTTAAAG GGCTAGCTACAACGA ACCCACTT
4144





1639
AAAGUGGU G CCAUCAUC
1296
GATGATGG GGCTAGCTACAACGA ACCACTTT
4145





1657
ACACAGUC G CUUUGGGG
1297
CCCCAAAG GGCTAGCTACAACGA GACTGTGT
4146





1672
GGCCCUCU G CAGCUCAA
1298
TTGAGCTG GGCTAGCTACAACGA AGAGGGCC
4147





1726
AGACAUAU G CUUCAGAU
1300
ATCTGAAG GGCTAGCTACAACGA ATATGTCT
4148





1762
UCAUUGAU G CUUUUGGG
1302
CCCAAAAG GGCTAGCTACAACGA ATCAATGA
4149





1805
CUCUCAGC G CUCCAUCC
1303
GGATGGAG GGCTAGCTACAACGA GCTGAGAG
4150





1923
UGGACAAC G CAGCCUCC
1307
GGAGGCTG CGCTAGCTACAACGA GTTGTCCA
4151





2026
CAGGCAUU G CUAAGGUU
1308
AACCTTAG GGCTAGCTACAACGA AATGCCTG
4152





2055
UACAGUCU G CAAGCAAG
1309
CTTGCTTG GGCTAGCTACAACGA AGACTGTA
4153





2098
CGUCCCGU G CGUCCAAU
1312
ATTGGACG GGCTAGCTACAACGA ACGGGACG
4154





2107
CGUCCAAU G CUACCCUG
1313
CAGGGTAG GGCTAGCTACAACGA ATTGGACG
4155





2115
GCUACCCU G CCUCCAAU
1314
ATTGGAGG GGCTAGCTACAACGA AGGGTAGC
4156





2185
UAGUUUAU G CAAAUAUU
1317
AATATTTG GGCTAGCTACAACGA ATAAACTA
4157





2195
AAAUAUUC G CCAAGGAG
1318
CTCCTTGG GGCTAGCTACAACGA GAATATTT
4158





2296
GAGCAGGU G CUGAUGCU
1322
AGCATCAG GGCTAGCTACAACGA ACCTGCTC
4159





2302
GUGCUGAU G CUACUAAG
1324
CTTAGTAG GGCTAGCTACAACGA ATCAGCAC
4160





2376
GUAAAAGU G CGGGCUCU
1328
AGAGCCCG GGCTAGCTACAACGA ACTTTTAC
4161





2398
GAGUUAAC G CAGCCAGA
1329
TCTGGCTG GGCTAGCTACAACGA GTTAACTC
4162





2584
UCCCAAAU G CUCCCAUA
1337
TATGGGAG GGCTAGCTACAACGA ATTTGGGA
4163





2788
AUACUACU G CUCUCAUC
1348
GATGAGAG GGCTAGCTACAACGA AGTAGTAT
4164





2878
UUUUCAUU G CUAUUCAG
1351
CTGAATAG GGCTAGCTACAACGA AATGAAAA
4165





2929
CCAACAUU G CACGAGUA
1355
TACTCGTG GGCTAGCTACAACGA AATGTTGG
4166





2964
CAGACUCC G CCAGAGAC
1357
GTCTCTGG GGCTAGCTACAACGA GGAGTCTG
4167





2995
AAACGUCU G CUCCUUGU
1360
ACAAGGAG GGCTAGCTACAACGA AGACGTTT
4168





3078
GGAGAACU G CAGCUGUC
1361
GACAGCTG GGCTAGCTACAACGA AGTTCTCC
4169





3294
AAUAAAAU G CUAAACAA
1366
TTGTTTAG GGCTAGCTACAACGA ATTTTATT
4170





27
AAAUGGAU G UGGAAUAU
1367
ATATTCCA GGCTAGCTACAACGA ATCCATTT
4171





52
AUUUUCUU G UUUAAGGG
1368
CCCTTAAA GGCTAGCTACAACGA AAGAAAAT
4172





75
GAAGAGGU G UUGAGGUU
1369
AACCTCAA GGCTAGCTACAACGA ACCTCTTC
4173





86
GAGGUUAU G UCAAGCAU
1370
ATGCTTGA GGCTAGCTACAACGA ATAACCTC
4174





155
AAGAUAUU G UUAUCAUU
1371
AATGATAA GGCTAGCTACAACGA AATATCTT
4175





221
AAAGACCU G UGAUAAAC
1372
GTTTATCA GGCTAGCTACAACGA AGGTCTTT
4176





253
GGAAACGU G UGUCUAUA
1373
TATAGACA GGCTAGCTACAACGA ACGTTTCC
4177





255
AAACGUGU G UCUAUAUU
1374
AATATAGA GGCTAGCTACAACGA ACACGTTT
4178





273
UCAUAUCU G UAUAUAUA
1375
TATATATA GGCTAGCTACAACGA AGATATGA
4179





344
AGGGAGAU G UACAGCAA
1376
TTGCTGTA GGCTAGCTACAACGA ATCTCCCT
4180





373
AGAGUUCU G UGUUCAUC
1377
GATGAACA GGCTAGCTACAACGA AGAACTCT
4181





375
AGUUCUGU G UUCAUCUU
1378
AAGATGAA GGCTAGCTACAACGA ACAGAACT
4182





457
AAGGCAUU G UCGUUGCA
1379
TGCAACGA GGCTAGCTACAACGA AATGCCTT
4183





478
ACCCCAAU G UGCCAGAA
1380
TTCTGGCA GGCTAGCTACAACGA ATTGGGGT
4184





537
GCAUCUCU G UAUCUGUU
1381
AACAGATA GGCTAGCTACAACGA AGAGATGC
4185





543
CUGUAUCU G UUUGAAGC
1382
GCTTCAAA GGCTAGCTACAACGA AGATACAG
4186





580
UCAAAAAU G UUGCCAUU
1383
AATGGCAA GGCTAGCTACAACGA ATTTTTGA
4187





625
CUGACUAU G UGAGACCA
1384
TGGTCTCA GGCTAGCTACAACGA ATAGTCAG
4188





661
AUGCUGAU G UUCUGGUU
1385
AACCAGAA GGCTAGCTACAACGA ATCAGCAT
4189





725
GGGCAACU G UGGAGAGA
1386
TCTCTCCA GGCTAGCTACAACGA AGTTGCCC
4190





814
AGGCAUUU G UCCAUGAG
1387
CTCATGGA GGCTAGCTACAACGA AAATGCCT
4191





911
AGUAAGAU G UUCACCAC
1388
CTGCTGAA GGCTAGCTACAACGA ATCTTACT
4192





937
GUACAAAU G UAGUAAAG
1389
CTTTACTA GGCTAGCTACAACGA ATTTGTAC
4193





950
AAAGAAGU G UCAGGGAG
1390
CTCCCTGA GGCTAGCTACAACGA ACTTCTTT
4194





965
AGGCAGCU G UUACACCA
1391
TGGTGTAA GGCTAGCTACAACGA AGCTGCCT
4195





1019
AAAAGGAU G UGAGUUUG
1392
CAAACTCA GGCTAGCTACAACGA ATCCTTTT
4196





1027
GUGAGUUU G UUCUCCAA
1393
TTGGAGAA GGCTAGCTACAACGA AAACTCAC
4197





1065
UCUAUAAU G UUUGCACA
1394
TGTGCAAA GGCTAGCTACAACGA ATTATAGA
4198





1078
CACAACAU G UUGAUUCU
1395
AGAATCAA GGCTAGCTACAACGA ATGTTGTG
4199





1100
UGAAUUCU G UACAGAAC
1396
GTTCTGTA GGCTAGCTACAACGA AGAATTCA
4200





1270
AAAGAAUU G UGUGUUUA
1397
TAAACACA GGCTAGCTACAACGA AATTCTTT
4201





1272
AGAAUUGU G UGUUUAGU
1398
ACTAAACA GGCTAGCTACAACGA ACAATTCT
4202





1274
AAUUGUGU G UUUAGUCC
1399
GGACTAAA GGCTAGCTACAACGA ACACAATT
4203





1414
CUGCCCAU G UACAAAGU
1400
ACTTTGTA GGCTAGCTACAACGA ATGGGCAC
4204





1534
CAUUUACU G UGAUUAGG
1401
CCTAATCA GGCTAGCTACAACGA AGTAAATG
4205





1573
CUCAAAUU G UGCUGCUG
1402
CAGCAGCA GGCTAGCTACAACGA AATTTCAG
4206





1695
CAGGAGCU G UCCAAAAU
1403
ATTTTGGA GGCTAGCTACAACGA AGCTCCTC
4207





1795
AUGGAGCU G UCUCUCAG
1404
CTGAGAGA GGCTAGCTACAACGA AGCTCCAT
4208





1902
GACACUUU G UUUCUUAU
1405
ATAAGAAA GGCTAGCTACAACGA AAAGTCTC
4209





1978
GUGGCUUU G UAGUGGAC
1406
GTCCACTA GGCTAGCTACAACGA AAAGCCAC
4210





2086
CCCUGACU G UCACGUCC
1407
GGACGTGA GGCTAGCTACAACGA AGTCAGGG
4211





2227
GGGCCAGU G UCACAGCC
1408
GGCTGTGA GGCTAGCTACAACGA ACTGGCCC
4212





2320
AUGACGGU G UCUACUCA
1409
TGAGTACA GGCTAGCTACAACGA ACCGTCAT
4213





2368
GAUACAGU G UAAAAGUG
1410
CACTTTTA GGCTAGCTACAACGA ACTCTATC
4214





2439
GGAGCACU G UACAUACC
1411
GGTATGTA GGCTAGCTACAACGA AGTGCTCC
4215





2512
AGGAUGAU G UUCAACAC
1412
GTGTTGAA GGCTAGCTACAACGA ATCATCCT
4216





2529
AAGCAAGU G UGUUUCAG
1413
CTGAAACA GGCTAGCTACAACGA ACTTGCTT
4217





2531
GCAAGUCU G UUUCAGCA
1414
TGCTGAAA GGCTAGCTACAACGA ACACTTGC
4218





2563
GCUCAUUU G UGGCUUCU
1415
AGAAGCCA GGCTAGCTACAACGA AAATGAGC
4219





2575
CUUCUGAU G UCCCAAAU
1416
ATTTGGGA GGCTAGCTACAACGA ATCAGAAG
4220





2829
GUCUUUUU G UUUAAACC
1417
GGTTTAAA GGCTAGCTACAACGA AAAAAGAC
4221





2890
UUCAGGCU G UUGAUAAG
1418
CTTATCAA GGCTAGCTACAACGA AGCCTGAA
4222





2943
GUAUCUUU G UUUAUUCC
1419
GGAATAAA GGCTAGCTACAACGA AAAGATAC
4223





3002
UGCUCCUU G UCCUAAUA
1420
TATTAGGA GGCTAGCTACAACGA AAGGAGCA
4224





3057
AAAAUUAU G UGGAAGUG
1421
CACTTCCA GGCTAGCTACAACGA ATAATTTT
4225





3084
CUGCACCU G UCAAUAGC
1422
GCTATTGA GGCTAGCTACAACGA AGCTGCAG
4226





3109
GAAUUUUU G UCAGAUAA
1423
TTATCTGA GGCTAGCTACAACGA AAAAATTC
4227





3166
UCUAAAAU G UAUUUUAG
1424
CTAAAATA GGCTAGCTACAACGA ATTTTAGA
4228





3182
GACUUCCU G UAGGGGGC
1425
GCCCCCTA GGCTAGCTACAACGA AGGAAGTC
4229





3272
GACUUCCU G UAGGGGGC
1425
GCCCCCTA GGCTAGCTACAACGA AGGAAGTC
4229





3203
UACUAAAU G UAUAUACU
1426
ACTATATA GGCTAGCTACAACGA ATTTAGTA
4230





3227
UACUAAAU G UAUUCCUG
1427
CAGGAATA GGCTAGCTACAACGA ATTTAGTA
4231





3235
GUAUUCCU G UAGGGGGC
1428
GCCCCCTA GGCTAGCTACAACGA AGGAATAC
4232





3256
UACUAAAU G UAUUUUAG
1429
CTAAAATA GGCTAGCTACAACGA ATTTAGGTA
4233





15
UGCUUUUG G UACAAAUG
1430
CATTTGTA GGCTAGCTACAACGA CAAAAGCA
4234





63
UAAGGGGA G CAUGAAGA
1431
TCTTCATG GGCTAGCTACAACGA TCCCCTTA
4235





73
AUGAAGAG G UCUUGAGG
1432
CCTCAACA GGCTAGCTACAACGA CTCTTCAT
4236





81
GUGUUGAG G UUAUGUCA
1433
TGACATAA GGCTAGCTACAACGA CTCAACAC
4237





91
UAUGUCAA G CAUCUGGC
1434
GCCAGATG GGCTAGCTACAACGA TTGACATA
4238





98
AGCAUCUG G CACAGCUG
1435
CAGCTGTG GGCTAGCTACAACGA CAGATGCT
4239





103
CUGGCACA G CUGAAGGC
1436
GCCTTCAG GGCTAGCTACAACGA TGTGCCAG
4240





110
AGCUGAAG G CAGAUGGA
1437
TCCATCTG GGCTAGCTACAACGA CTTCAGCT
4241





130
AUUUACAA G UACGCAAU
1438
ATTGCGTA GGCTAGCTACAACGA TTGTAAAT
4242





182
AGACAAGA G CAAUAGUA
1439
TACTATTG GGCTAGCTACAACGA TCTTGTCT
4243





188
GACCAAUA G UAAAACAC
1440
GTGTTTTA GGCTAGCTACAACGA TATTGCTC
4244





202
CACAUCAG G UCAGGGGG
1441
CCCCCTGA GGCTAGCTACAACGA CTGATCTC
4245





210
GUCAGGGG G UUAAAGAC
1442
GTCTTTAA GGCTAGCTACAACGA CCCCTGAC
4246





242
UCCGAUAA G UUGGAAAC
1443
GTTTCCAA GGCTAGCTACAACGA TTATCGGA
4247





251
UUGGAAAC G UGUGUCUA
1444
TAGACACA GGCTAGCTACAACGA GTTTCCAA
4248





287
AUAUAAUG G UAAAGAAA
1445
TTTCTTTA GGCTAGCTACAACGA CATTATAT
4249





305
ACACCUUC G UAACCCGC
1446
GCGGGTTA GGCTAGCTACAACGA GAAGGTGT
4250





349
GAUGUACA G CAAUGGGG
1447
CCCCATTG GGCTAGCTACAACGA TGTACATC
4251





357
GCAAUGGG G CCAUUUAA
1448
TTAAATGG GGCTAGCTACAACGA CCCATTGC
4252





368
AUUUAAGA G UUCUGUGU
1449
ACACAGAA GGCTAGCTACAACGA TCTTAAAT
4253





406
UAGAAGGG G CCCUGAGU
1450
ACTCAGGG GGCTAGCTACAACGA CCCTTCTA
4254





413
GGCCCUGA G UAAUUCAC
1451
GTGAATTA GGCTAGCTACAACGA TCAGGGCC
4255





429
CUCAUUCA G CUGAACAA
1452
TTGTTCAG GGCTAGCTACAACGA TGAATGAG
4256





443
CAACAAUG G CUAUGAAG
1453
CTTCATAG GGCTAGCTACAACGA CATTGTTG
4257





452
CUAUGAAG G CAUUGUCG
1454
CGACAATG GGCTAGCTACAACGA CTTCATAG
4258





460
GCAUUGUC G UUGCAAUC
1455
GATTGCAA GGCTAGCTACAACGA GACAATGC
4259





520
AGGACAUG G UGACCCAG
1456
CTGGGTCA GGCTAGCTACAACGA CATGTCCT
4260





529
UGACCCAG G CAUCUCUG
1457
CAGAGATG GGCTAGCTACAACGA CTGGGTCA
4261





550
UGUUUGAA G CUACAGGA
1458
TCCTGTAG GGCTAGCTACAACGA TTCAAACA
4262





561
ACAGGAAA G CGAUUUUA
1459
TAAAATCG GGCTAGCTACAACGA TTTCCTGT
4263





616
AGACAAAG G CUGACUAU
1460
ATAGTCAG GGCTAGCTACAACGA CTTTGTCT
4264





667
AUGUUCUG G UUGCUGAG
1461
CTCAGCAA GGCTAGCTACAACGA CAGAACAT
4265





675
GUUGCUGA G UCUACUCC
1462
GGAGTAGA GGCTAGCTACAACGA TCAGCAAC
4266





689
UCCUCCAG G UAAUGAUG
1463
CATCATTA GGCTAGCTACAACGA CTGGAGGA
4267





711
UACACUGA G CAGAUGGG
1464
CCCATCTG GGCTAGCTACAACGA TCAGTGTA
4268





719
GCAGAUGG G CAACUGUG
1465
CACAGTTG GGCTAGCTACAACGA CCATCTGC
4269





737
AGAGAAGG G UGAAAGGA
1466
TCCTTTCA GGCTACCTACAACGA CCTTCTCT
4270





780
GGAAAAAA G UUAGCUGA
1467
TCAGCTAA GGCTAGCTACAACGA TTTTTTCC
4271





784
AAAAGUUA G CUGAAUAU
1468
ATATTCAG GGCTAGCTACAACGA TAACTTTT
4272





803
ACCACAAG G UAAGGCAU
1469
ATGCCTTA GGCTAGCTACAACGA CTTGTGGT
4273





808
AAGGUAAG G CAUUUGUC
1470
GACAAATG GGCTAGCTACAACGA CTTACCTT
4274





822
GUCCAUGA G UGGGCUCA
1471
TGAGCCCA GGCTAGCTACAACGA TCATGGAC
4275





826
AUGAGUGG G CUCAUCUA
1472
TAGATGAG GGCTAGCTACAACGA CCACTCAT
4276





844
GAUGGGGA G UAUUUGAC
1473
GTCAAATA GGCTAGCTACAACGA TCCCCATC
4277





855
UUUGACGA G UACAAUAA
1474
TTATTGTA GGCTAGCTACAACGA TCGTCAAA
4278





901
GAAUACAA G CAGUAAGA
1475
TCTTACTG GGCTAGCTACAACGA TTGTATTC
4279





904
UACAAGCA G UAAGAUGU
1476
ACATCTTA GGCTAGCTACAACGA TGCTTGTA
4280





916
GAUGUUCA G CAGGUAUU
1477
AATACCTG GGCTAGCTACAACGA TGAACATC
4281





920
UUCAGCAG G UAUUACUG
1478
CAGTAATA GGCTAGCTACAACGA CTGCTGAA
4282





929
UAUUACUG G UACAAAUG
1479
CATTTGTA GGCTAGCTACAACGA CAGTAATA
4283





940
CAAAUGUA G UAAAGAAG
1480
CTTCTTTA GGCTAGCTACAACGA TACATTTG
4284





948
GUAAAGAA G UGUCAGGG
1481
CCCTGACA GGCTAGCTACAACGA TTCTTTAC
4285





959
UCAGGGAG G CAGCUGUU
1482
AACAGCTG GGCTAGCTACAACGA CTCCCTGA
4286





962
GGGAGGCA G CUGUUACA
1483
TCTAACAG GGCTAGCTACAACGA TGCCTCCC
4287





994
UCAAUAAA G UUACAGGA
1484
TCCTGTAA GGCTAGCTACAACGA TTTATTGA
4288





1023
GGAUGUGA G UUUGUUCU
1485
AGAACAAA GGCTAGCTACAACGA TCACATCC
4289





1054
CGGAGAAG G CUUCUAUA
1486
TATAGAAG GGCTAGCTACAACGA CTTCTCCG
4290





1090
AUUCUAUA G UUGAAUUC
1487
GAATTCAA GGCTAGCTACAACGA TATAGAAT
4291





1126
ACAAAGAA G CUCCAAAC
1488
CTTTCCAG GGCTAGCTACAACGA TTCTTTGT
4292





1137
CCAAACAA G CAAAAUCA
1489
TCATTTTC GGCTAGCTACAACGA TTGTTTCC
4293





1163
UCUCCCAA G CACAUGGG
1490
CCCATGTG GGCTAGCTACAACGA TTCGGAGA
4294





1174
CAUGGGAA G UGAUCCGU
1491
ACGGATCA GGCTAGCTACAACGA TTCCCATC
4295





1181
AGUGAUCC G UGAUUCUG
1492
CAGAATCA GGCTAGCTACAACGA GGATCACT
4296





1224
ACAACACA G CCACCAAA
1493
TTTGCTGG GGCTAGCTACAACGA TGTGTTGT
4297





1279
UGUGUUUA G UCCUUGAC
1494
GTCAAGGA GGCTAGCTACAACGA TAAACACA
4298





1298
AUCUCCAA G CAUGGCGA
1495
TCGCCATG GGCTAGCTACAACGA TTCCAGAT
4299





1303
GAAGCAUG G CGACUGGU
1496
ACCAGTCC GGCTAGCTACAACGA CATGCTTC
4300





1310
GGCGACUG G UAACCGCC
1497
GGCGGTTA GGCTAGCTACAACGA CAGTCGCC
4301





1336
UGAAUCAA G CAGGCCAG
1498
CTGGCCTC GGCTAGCTACAACGA TTGATTCA
4302





1340
UCAAGCAG G CCAGCUUU
1499
AAAGCTGG GGCTAGCTACAACGA CTGCTTGA
4303





1344
GCAGGCCA G CUUUUCCU
1500
AGGAAAAG GGCTAGCTACAACGA TGGCCTGC
4304





1363
UGCAGACA G UUGAGCUG
1501
CAGCTCAA GGCTAGCTACAACGA TGTCTGCA
4305





1368
ACAGUUGA G CUGGGGUC
1502
GACCCCAG GGCTAGCTACAACGA TCAACTGT
4306





1374
GAGCUGGG G UCCUGGGU
1503
ACCCAGGA GGCTAGCTACAACGA CCCAGCTC
4307





1381
GGUCCUGG G UUGGGAUG
1504
CATCCCAA GGCTAGCTACAACGA CCAGGACC
4308





1390
UUGGGAUG G UGACAUUU
1505
AAATGTCA GGCTAGCTACAACGA CATCCCAA
4309





1403
AUUUGACA G UGCUGCCC
1506
GGGCAGCA GGCTAGCTACAACGA TGTCAAAT
4310





1421
UGUACAAA G UGAACUCA
1507
TGAGTTCA GGCTAGCTACAACGA TTTGTACA
4311





1442
GAUAGACA G UGGCAGUG
1508
CACTGCCA GGCTAGCTACAACGA TGTTTATC
4312





1445
AAACAGUG G CAGUGACA
1509
TGTCACTG GGCTAGCTACAACGA CACTGTTT
4313





1448
CAGUGGCA G UGACAGGG
1510
CCCTGTCA GGCTAGCTACAACGA TGCCACTG
4314





1483
UACCUGCA G CAGCUUCA
1511
TGAAGCTG GGCTAGCTACAACGA TGCAGGTA
4315





1486
CUGCAGCA G CUUCAGGA
1512
TCCTGAAG GGCTAGCTACAACGA TGCTGCAG
4316





1500
GGAGGGAC G UCCAUCUG
1513
CAGATGGA GGCTAGCTACAACGA GTCCCTCC
4317





1511
CAUCUGCA G CGGGCUUC
1514
GAAGCCCG GGCTAGCTACAACGA TGCAGATG
4318





1515
UGCAGCGG G CUUCGAUC
1515
GATCGAAG GGCTAGCTACAACGA CCGCTGCA
4319





1525
UUCGAUCG G CAUUUACU
1516
AGTAAATG GGCTAGCTACAACGA CGATCGAA
4320





1607
CACUAUAA G UGGGUGCU
1517
AGCACCCA GGCTAGCTACAACGA TTATAGTG
4321





1611
AUAAGUGG G UGCUUUAA
1518
TTAAAGCA GGCTAGCTACAACGA CCACTTAT
4322





1624
UUAACGAG G UCAAACAA
1519
TTGTTTGA GGCTAGCTACAACGA CTCGTTAA
4323





1634
CAAACAAA G UGGUGCCA
1520
TGGCACCA GGCTAGCTACAACGA TTTGTTTG
4324





1637
ACAAAGUG G UGCCAUCA
1521
TGATGGCA GGCTAGCTACAACGA CACTTTGT
4325





1654
UCCACACA G UCGCUUUG
1522
CAAAGCGA GGCTAGCTACAACGA TGTGTGGA
4326





1665
GCUUUGGG G CCCUCUGC
1523
GCAGAGGG GGCTAGCTACAACGA CCCAAAGC
4327





1675
CCUCUGCA G CUCAAGAA
1524
TTCTTGAG GGCTAGCTACAACGA TGCAGAGG
4328





1692
CUAGAGGA G CUGUCCAA
1525
TTGGACAG GGCTAGCTACAACGA TCCTCTAG
4329





1712
GACAGGAG G UUUACAGA
1526
TCTGTAAA GGCTAGCTACAACGA CTCCTGTC
4330





1738
CAGAUCAA G UUCAGAAC
1527
GTTCTGAA GGCTAGCTACAACGA TTGATCTG
4331





1751
GAACAAUG G CCUCAUUG
1528
CAATGAGG GGCTAGCTACAACGA CATTGTTC
4332





1771
CUUUUGGG G CCCUUUCA
1529
TGAAAGGG GGCTAGCTACAACGA CCCAAAAG
4333





1792
GAAAUGGA G CUGUCUCU
1530
AGAGACAG GGCTAGCTACAACGA TCCATTTC
4334





1803
GUCUCUCA G CGCUCCAU
1531
ATGGAGCG GGCTAGCTACAACGA TGAGAGAC
4335





1815
UCCAUCCA G CUUGAGAG
1532
CTCTCAAG GGCTAGCTACAACGA TGGATGGA
4336





1823
GCUUGAGA G UAAGGGAU
1533
ATCCCTTA GGCTAGCTACAACGA TCTCAAGC
4337





1847
CCAGAACA G CCAGUGGA
1534
TCCACTGG GGCTAGCTACAACGA TGTTCTGG
4338





1851
AACAGCCA G UGGAUGAA
1535
TTCATCCA GGCTAGCTACAACGA TGGCTGTT
4339





1862
GAUGAAUG G CACAGUGA
1536
TCACTGTG GGCTAGCTACAACGA CATTCATC
4340





1867
AUGGCACA G UGAUCGUG
1537
CACGATCA GGCTAGCTACAACGA TGTGCCAT
4341





1873
CAGUGAUC G UGGACAGC
1538
GCTGTCCA GGCTAGCTACAACGA GATCACTG
4342





1880
CGUGGACA G CACCGUGG
1539
CCACGGTG GGCTAGCTACAACGA TGTCCACG
4343





1885
ACAGCACC G UGGGAAAG
1540
CTTTCCCA GGCTAGCTACAACGA GGTGCTGT
4344





1926
ACAACGCA G CCUCCCCA
1541
TGGGGAGG GGCTAGCTACAACGA TGCGTTGT
4345





1955
GGAUCCCA G UGGACAGA
1542
TCTGTCCA GGCTAGCTACAACGA TGGGATCC
4346





1965
GGACAGAA G CAAGGUGG
1543
CCACCTTG GGCTAGCTACAACGA TTCTGTCC
4347





1970
GAAGCAAG G UGGCUUUG
1544
CAAAGCCA GGCTAGCTACAACGA CTTGCTTC
4348





1973
GCAAGGUG G CUUUGUAG
1545
CTACAAAG GGCTAGCTACAACGA CACCTTGC
4349





1981
GCUUUGUA G UGGACAAA
1546
TTTGTCCA GGCTAGCTACAACGA TACAAAGC
4350





2002
CCAAAAUG G CCUACCUC
1547
GAGGTAGG GGCTAGCTACAACGA CATTTTGG
4351





2021
AAUCCCAG G CAUUGCUA
1548
TAGCAATG GGCTAGCTACAACGA CTGGGATT
4352





2032
UUGCUAAG G UUGGCACU
1549
AGTGCCAA GGCTAGCTACAACGA CTTAGCAA
4353





2036
UAAGGUUG G CACUUGGA
1550
TCCAAGTG GGCTAGCTACAACGA CAACCTTA
4354





2051
GAAAUACA G UCUGCAAG
1551
CTTGCAGA GGCTAGCTACAACGA TGTATTTC
4355





2059
GUCUGCAA G CAAGCUCA
1552
TGAGCTTG GGCTAGCTACAACGA TTGCAGAC
4356





2063
GCAAGCAA G CUCACAAA
1553
TTTGTGAG GGCTAGCTACAACGA TTGCTTGC
4357





2091
ACUGUCAC G UCCCGUGC
1554
GCACGGGA GGCTAGCTACAACGA GTGACAGT
4358





2096
CACGUCCC G UGCGUCCA
1555
TGGACGCA GGCTAGCTACAACGA GGGACGTG
4359





2100
UCCCGUGC G UCCAAUGC
1556
GCATTGGA GGCTAGCTACAACGA GCACGGGA
4360





2128
CAAUUACA G UGACUUCC
1557
GGAAGTCA GGCTAGCTACAACGA TGTAATTG
4361





2156
GGACACCA G CAAUUCC
1558
GGAATTTG GGCTAGCTACAACGA TGGTGTCC
4362





2168
AUUCCCCA G CCCUCUGG
1559
CCAGAGGG GGCTAGCTACAACGA TGGGGAAT
4363





2176
GCCCUCUG G UAGUUUAU
1560
ATAAACTA GGCTAGCTACAACGA CAGAGGGC
4364





2179
CUCUGGUA G UUUAUGCA
1561
TGCATAAA GGCTAGCTACAACGA TACCAGAG
4365





2203
GCCAAGGA G CCUCCCCA
1562
TGGGGAGG GGCTAGCTACAACGA TCCTTGGC
4366





2221
UUCUCAGG G CCAGUGUC
1563
GACACTGG GGCTAGCTACAACGA CCTGAGAA
4367





2225
CAGGGCCA G UGUCACAC
1564
CTGTGACA GGCTAGCTACAACGA TGGCCCTG
4368





2233
GUGUCACA G CCCUCAUU
1565
AATCAGGG GGCTAGCTACAACGA TGTGACAC
4369





2248
UUGAAUCA G UGAAUGGA
1566
TCCATTCA GGCTAGCTACAACGA TGATTCAA
4370





2263
GAAAAACA G UUACCUUG
1567
CAAGGTAA GGCTAGCTACAACGA TGTTTTTC
4371





2290
AUAAUGGA G CAGGUGCU
1568
AGCACCTG GGCTAGCTACAACGA TCCATTAT
4372





2294
UCGAGCAG G UCCUGAUG
1569
CATCAGCA GGCTAGCTACAACGA CTGCTCCA
4373





2318
GGAUGACG G UGUCUACU
1570
ACTAGACA CGCTAGCTACAACGA CGTCATCC
4374





2331
UACUCAAG G UAUUUCAC
1571
GTCAAATA GGCTAGCTACAACCA CTTCACTA
4375





2357
CACGAAUG G UAGAUACA
1572
TGTATCTA GGCTAGCTACAACGA CATTCGTG
4376





2366
UAGAUACA G UGUAAAAG
1573
CTTTTACA GGCTAGCTACAACGA TGTATCTA
4377





2374
GUGUAAAA G UGCGGGCU
1574
AGCCCGCA GGCTAGCTACAACGA TTTTACAC
4378





2380
AAGUGCGG G CUCUGGGA
1575
TCCCAGAG GGCTAGCTACAACGA CCGCACTT
4379





2392
UGGGAGGA G UUAACGCA
1576
TGCGTTAA GGCTAGCTACAACGA TCCTCCCA
4380





2401
UUAACGCA G CCAGACGG
1577
CCGTCTGG GGCTAGCTACAACGA TGCGTTAA
4381





2413
GACGGAGA G UGAUACCC
1578
GGGTATCA GGCTAGCTACAACGA TCTCCGTC
4382





2424
AUACCCCA G CAGAGUGG
1579
CCACTCTG GGCTAGCTACAACGA TGGGGTAT
4383





2429
CCAGCAGA G UGGAGCAC
1580
GTGCTCCA GGCTAGCTACAACGA TCTGCTGG
4384





2434
AGAGUGGA G CACUGUAC
1581
GTACAGTG GGCTAGCTACAACGA TCCACTCT
4385





2450
CAUACCUG G CUGGAUUG
1582
CAATCCAG GGCTAGCTACAACGA CAGGTATG
4386





2523
CAACACAA G CAAGUGUG
1583
CACACTTG CGCTAGCTACAACGA TTGTCTTG
4387





2527
ACAAGCAA G UGUGUUUC
1584
GAAACACA GGCTAGCTACAACGA TTGCTTCT
4388





2537
GUCUUUCA G CAGAACAU
1585
ATGTTCTG GCCTAGCTACAACGA TGAAACAC
4389





2555
CUCGGGAG G CUCAUUUG
1586
CAAATGAG GGCTAGCTACAACGA CTCCCGAG
4390





2566
CAUUUGUG G CUUCUGAU
1587
ATCAGAAG GGCTAGCTACAACGA CACAAATG
4391





2612
CCCACCUG G CCAAAUCA
1588
TGATTTGG GGCTAGCTACAACGA CAGGTCCC
4392





2632
ACCUGAAG G CGGAAAUU
1589
AATTTCCG GGCTAGCTACAACGA CTTCAGGT
4393





2648
UCACGGGG G CAGUCUCA
1590
TGACACTG GGCTAGCTACAACGA CCCCGTGA
4394





2651
CGGGGGCA G UCUCAUUA
1591
TAATGAGA GGCTAGCTACAACGA TGCCCCCG
4395





2674
CUUGGACA G CUCCUGGG
1592
CCCAGGAG GGCTAGCTACAACGA TGTCCAAG
4396





2704
AUGGAACA G CUCACAAG
1593
CTTGTGAG GGCTAGCTACAACGA TGTTCCAT
4397





2712
GCUCACAA G UAUAUCAU
1594
ATGATATA GCCTAGCTACAACGA TTGTCAGC
4398





2729
UCGAAUAA G UACAAGUA
1595
TACTTGTA GGCTAGCTACAACGA TTATTCCA
4399





2735
AAGUACAA G UAUUCUUG
1596
CAAGAATA GGCTAGCTACAACGA TTGTACTT
4400





2757
AGAGACAA G UUCAAUGA
1597
TCATTGAA GGCTAGCTACAACGA TTGTCTCT
4401





2776
CUCUUCAA G UGAAUACU
1598
AGTATTCA GGCTAGCTACAACGA TTGAACAG
4402





2806
CAAAGGAA G CCAACUCU
1599
AGAGTTGG GGCTAGCTACAACGA TTCCTTTG
4403





2821
CUGAGGAA G UCUUUUUG
1600
CAAAAAGA GGCTAGCTACAACGA TTCCTCAG
4404





2861
UGAAAAUG G CACAGAUC
1601
GATCTGTG GGCTAGCTACAACGA CATTTTCA
4405





2887
CUAUUCAG G CUGUUGAU
1602
ATCAACAG GGCTAGCTACAACGA CTGAATAG
4406





2899
UUGAUAAC G UCGAUCUG
1603
CAGATCGA GGCTAGCTACAACGA CTTATCAA
4407





2935
UUGCACGA G UAUCUUUG
1604
CAAAGATA GGCTAGCTACAACGA TCGTGCAA
4408





2978
GACACCUA G UCCUGAUG
1605
CATCAGGA GGCTAGCTACAACGA TAGGTGTC
4409





2991
GAUGAAAC G UCUGCUCC
1606
GGAGCAGA GGCTAGCTACAACGA GTTTCATC
4410





3023
UAUCAACA G CACCAUUC
1607
GAATGGTG GGCTAGCTACAACGA TGTTGATA
4411





3035
CAUUCCUG G CAUUCACA
1608
TGTGAATG GGCTAGCTACAACGA CAGGAATG
4412





3063
AUGUGGAA G UGGAUAGG
1609
CCTATCCA GGCTAGCTACAACGA TTCCACAT
4413





3081
GAACUGCA G CUGUCAAU
1610
ATTGACAG GGCTAGCTACAACGA TGCAGTTC
4414





3091
UGUCAAUA G CCUAGGGC
1611
GCCCTAGG GGCTAGCTACAACGA TATTGACA
4415





3098
AGCCUAGG G CUGAAUUU
1612
AUATTCAG GGCTAGCTACAACGA CCTAGGCT
4416





3189
UGUAGGGG G CGAUAUAC
1613
GTATATCG GGCTAGCTACAACGA CCCCTACA
4417





3242
UGUAGGGG G CGAUAUAC
1613
GTATATCG GGCTAGCTACAACGA CCCCTACA
4417





3210
UGUAUAUA G UACAUUUA
1614
TAAATGTA GGCTAGCTACAACGA TATATACA
4418





3279
UGUAGGGG G CGAUAAAA
1615
TTTTATCG GGCTAGCTACAACGA CCCCTACA
4419





21
UGGUACAA A UGGAUGUG
1616
CACATCCA GGCTAGCTACAACGA TTGTACCA
4420





25
ACAAAUGG A UGUGGAAU
1617
ATTCCACA GGCTAGCTACAACGA CCATTTGT
4421





32
GAUGUGGA A UAUAAUUG
1618
CAATTATA GGCTAGCTACAACGA TCCACATC
4422





37
GGAAUAUA A UUGAAUAU
1619
ATATTCAA GGCTAGCTACAACGA TATATTCC
4423





42
AUAAUUGA A UAUUUUCU
1620
AGAAAATA GGCTAGCTACAACGA TCAATTAT
4424





114
GAAGGCAG A UGGAAAUA
1621
TATTTCCA GGCTAGCTACAACGA CTGCCTTC
4425





120
AGAUGGAA A UAUUUACA
1622
TGTAAATA GGCTAGCTACAACGA TTCCATCT
4426





137
AGUACGCA A UUUGAGAC
1623
GTCTCAAA GGCTAGCTACAACGA TGCGTACT
4427





144
AAUUUGAG A CUAAGAUA
1624
TATCTTAG GGCTAGCTACAACGA CTCAAATT
4428





150
AGACUAAG A UAUUGUUA
1625
TAACAATA GGCTAGCTACAACGA CTTAGTCT
4429





176
UAUUGAAG A CAAGAGCA
1626
TGCTCTTG GGCTAGCTACAACGA CTTCAATA
4430





185
CAAGAGCA A UAGUAAAA
1627
TTTTACTA GGCTAGCTACAACGA TGCTCTTG
4431





193
AUAGUAAA A CACAUCAG
1628
CTGATGTG GGCTAGCTACAACGA TTTACTAT
4432





217
GGUUAAAG A CCUGUGAU
1629
ATCACAGG GGCTAGCTACAACGA CTTTAACC
4433





224
GACCUGUG A UAAACCAC
1630
GTGGTTTA GGCTAGCTACAACGA CACAGGTC
4434





228
UGUGAUAA A CCACUUCC
1631
GGAAGTGG GGCTAGCTACAACGA TTATCACA
4435





238
CACUUCCG A UAAGUUGG
1632
CCAACTTA GGCTAGCTACAACGA CGGAAGTG
4436





249
AGUUGGAA A CGUGUGUC
1633
GACACACG GGCTAGCTACAACGA TTCCAACT
4437





284
UAUAUAUA A UGGUAAAG
1634
CTTTACCA GGCTAGCTACAACGA TATATATA
4438





297
AAAGAAAG A CACCUUCG
1635
CGAAGGTG GGCTAGCTACAACGA CTTTCTTT
4439





308
CCUUCGUA A CCCGCAUU
1636
AATGCGGG GGCTAGCTACAACGA TACGAAGG
4440





331
AGAGAGGA A UCACAGGG
1637
CCCTGTGA GGCTAGCTACAACGA TCCTCTCT
4441





342
ACAGGGAG A UGUACAGC
1638
GCTGTACA GGCTAGCTACAACGA CTCCCTGT
4442





352
GUACAGCA A UGGGGCCA
1639
TGGCCCCA GGCTAGCTACAACGA TGCTGTAC
4443





385
UCAUCUUG A UUCUUCAC
1640
GTGAAGAA GGCTAGCTACAACGA CAAGATGA
4444





416
CCUGAGUA A UUCACUCA
1641
TGAGTGAA GGCTAGCTACAACGA TACTCAGG
4445





434
UCAGCUGA A CAACAAUG
1642
CATTGTTG GGCTAGCTACAACGA TCAGCTGA
4446





437
GCUGAACA A CAAUGGCU
1643
AGCCATTG GGCTAGCTACAACGA TGTTCAGC
4447





440
GAACAACA A UGGCUAUG
1644
CATAGCCA GGCTAGCTACAACGA TGTTGTTC
4448





466
UCGUUGCA A UCGACCCC
1645
GGGGTCGA GGCTAGCTACAACGA TGCAACGA
4449





470
UGCAAUCG A CCCCAAUG
1646
CATTGGGG GGCTAGCTACAACGA CGATTGCA
4450





476
CGACCCCA A UGUGCCAG
1647
CTGGCACA GGCTAGCTACAACGA TGGGGTCG
4451





488
GCCAGAAG A UGAAACAC
1648
GTGTTTCA GGCTAGCTACAACGA CTTCTGGC
4452





493
AAGAUGAA A CACUCAUU
1649
AATGAGTG GGCTAGCTACAACGA TTCATCTT
4453





504
CUCAUUCA A CAAAUAAA
1650
TTTATTTG GGCTAGCTACAACGA TGAATGAG
4454





508
UUCAACAA A UAAAGGAC
1651
GTCCTTTA GGCTAGCTACAACGA TTGTTGAA
4455





515
AAUAAAGG A CAUGGUGA
1652
TCACCATG GGCTAGCTACAACGA CCTTTATT
4456





523
ACAUGGUG A CCCAGGCA
1653
TGCCTGGG GGCTAGCTACAACGA CACCATGT
4457





564
GGAAAGCG A UUUUAUUU
1654
AAATAAAA GGCTAGCTACAACGA CGCTTTCC
4458





578
UUUCAAAA A UGUUGCCA
1655
TGGCAACA GGCTAGCTACAACGA TTTTGAAA
4459





592
CCAUUUUG A UUCCUGAA
1656
TTCAGGAA GGCTAGCTACAACGA CAAAATGG
4460





601
UUCCUGAA A CAUGGAAG
1657
CTTCCATG GGCTAGCTACAACGA TTCAGGAA
4461





610
CAUGGAAG A CAAAGGCU
1658
AGCCTTTG GGCTAGCTACAACGA CTTCCATG
4462





620
AAAGGCUG A CUAUGUGA
1659
TCACATAG GGCTAGCTACAACGA CAGCCTTT
4463





630
UAUGUGAG A CCAAAACU
1660
AGTTTTGG GGCTAGCTACAACGA CTCACATA
4464





636
AGACCAAA A CUUGAGAC
1661
GTCTCAAG GGCTAGCTACAACGA TTTGGTCT
4465





643
AACUUGAG A CCUACAAA
1662
TTTGTAGG GGCTAGCTACAACGA CTCAAGTT
4466





653
CUACAAAA A UGCUGAUG
1663
CATCAGCA GGCTAGCTACAACGA TTTTGTAG
4467





659
AAAUGCUG A UGUUCUGG
1664
CCAGAACA GGCTAGCTACAACGA CAGCATTT
4468





692
UCCAGGUA A UGAUGAAC
1665
GTTCATCA GGCTAGCTACAACGA TACCTGGA
4469





695
AGGUAAUG A UGAACCCU
1666
AGGGTTCA GGCTAGCTACAACGA CATTACCT
4470





699
AAUGAUGA A CCCUACAC
1667
GTGTAGGG GGCTAGCTACAACGA TCATCATT
4471





715
CUGAGCAG A UGGGCAAC
1668
GTTGCCCA GGCTAGCTACAACGA CTGCTCAG
4472





722
GAUGGGCA A CUGUGGAG
1669
CTCCACAG GGCTAGCTACAACGA TGCCCATC
4473





745
GUGAAAGG A UCCACCUC
1670
GAGGTGGA GGCTAGCTACAACGA CCTTTCAC
4474





761
CACUCCUG A UUUCAUUG
1671
CAATGAAA GGCTAGCTACAACGA CAGGAGTG
4475





789
UUAGCUGA A UAUGGACC
1672
GGTCCATA GGCTAGCTACAACGA TCAGCTAA
4476





795
GAAUAUGG A CCACAAGG
1673
CCTTGTGG GGCTAGCTACAACGA CCATATTC
4477





837
CAUCUACG A UGGGGAGU
1674
ACTCCCCA GGCTAGCTACAACGA CGTAGATG
4478





851
AGUAUUUG A CGAGUACA
1675
TGTACTCG GGCTAGCTACAACGA CAAATACT
4479





860
CGAGUACA A UAAUGAUG
1676
CATCATTA GGCTAGCTACAACGA TGTACTCG
4480





863
GUACAAUA A UGAUGAGA
1677
TCTCATCA GGCTAGCTACAACGA TATTGTAC
4481





866
CAAUAAUG A UGAGAAAU
1678
ATTTCTCA GGCTAGCTACAACGA CATTATTG
4482





873
GAUGAGAA A UUCUACUU
1679
AAGTAGAA GGCTAGCTACAACGA TTCTCATC
4483





887
CUUAUCCA A UGGAAGAA
1680
TTCTTCCA GGCTAGCTACAACGA TGGATAAG
4484





895
AUGGAAGA A UACAAGCA
1681
TGCTTGTA GGCTAGCTACAACGA TCTTCCAT
4485





909
GCAGUAAG A UGUUCAGC
1682
GCTGAACA GGCTAGCTACAACGA CTTACTGC
4486





935
UCGUACAA A UGUAGUAA
1683
TTACTACA GGCTAGCTACAACGA TTGTACCA
4487





978
ACCAAAAG A UGCACAUU
1684
AATGTGCA GGCTAGCTACAACGA CTTTTGGT
4488





989
CACAUUCA A UAAAGUUA
1685
TAACTTTA GGCTAGCTACAACGA TGAATGTG
4489





1002
GUUACAGG A CUCUAUGA
1686
TCATAGAG GGCTAGCTACAACGA CCTGTAAC
4490





1017
GAAAAAGG A UGUGAGUU
1687
AACTCACA GGCTAGCTACAACGA CCTTTTTC
4491





1035
GUUCUCCA A UCCCGCCA
1688
TGGCGGGA GGCTAGCTACAACGA TGGAGAAC
4492





1045
CCCGCCAG A CGGAGAAG
1689
CTTCTCCG GGCTAGCTACAACGA CTGGCGGG
4493





1063
CUUCUAUA A UGUUUGCA
1690
TGCAAACA GGCTAGCTACAACGA TATAGAAG
4494





1074
UUUGCACA A CAUGUUGA
1691
TCAACATG GGCTAGCTACAACGA TGTGCAAA
4495





1082
ACAUGUUG A UUCUAUAG
1692
CTATAGAA GGCTAGCTACAACGA CAACATGT
4496





1095
AUAGUUGA A UUCUGUAC
1693
GTACAGAA GGCTAGCTACAACGA TCAACTAT
4497





1107
UGUACAGA A CAAAACCA
1694
TGGTTTTG GGCTAGCTACAACGA TCTGTACA
4498





1112
AGAACAAA A CCACAACA
1695
TCTTGTGG GGCTAGCTACAACGA TTTGTTCT
4499





1118
AAACCACA A CAAAGAAG
1696
CTTCTTTG GGCTAGCTACAACGA TGTGGTTT
4500





1133
AGCUCCAA A CAAGCAAA
1697
TTTGCTTG GGCTAGCTACAACGA TTGGAGCT
4501





1142
CAAGCAAA A UCAAAAAU
1698
ATTTTTGA GGCTAGCTACAACGA TTTGCTTG
4502





1149
AAUCAAAA A UGCAAUCU
1699
AGATTGCA GGCTAGCTACAACGA TTTTGATT
4503





1154
AAAAUGCA A UCUCCGAA
1700
TTCGGAGA GGCTAGCTACAACGA TGCATTTT
4504





1177
GGGAAGUG A UCCGUGAU
1701
ATCACGGA GGCTAGCTACAACGA CACTTCCC
4505





1184
GAUCCGUG A UUCUGAGG
1702
CCTCAGAA GGCTAGCTACAACGA CACGGATC
4506





1193
UUCUGAGG A CUUUAAGA
1703
TCTTAAAG GGCTAGCTACAACGA CCTCAGAA
4507





1204
UUAAGAAA A CCACUCCU
1704
AGGAGTGG GGCTAGCTACAACGA TTTCTTAA
4508





1216
CUCCUAUG A CAACACAG
1705
CTGTGTTG GGCTAGCTACAACGA CATAGGAG
4509





1219
CUAUGACA A CACAGCCA
1706
TGGCTGTG GGCTAGCTACAACGA TGTCATAG
4510





1232
GCCACCAA A UCCCACCU
1707
AGGTGGGA GGCTAGCTACAACGA TTGGTGGC
4511





1255
UGCUGCAG A UUGGACAA
1708
TTGTCCAA GGCTAGCTACAACGA CTGCAGCA
4512





1260
CAGAUUGG A CAAAGAAU
1709
ATTCTTTG GGCTAGCTACAACGA CCAATCTG
4513





1267
GACAAAGA A UUGUGUGU
1710
ACACACAA GGCTAGCTACAACGA TCTTTGTC
4514





1286
AGUCCUUG A CAAAUCUG
1711
CAGATTTG GGCTAGCTACAACGA CAAGGACT
4515





1290
CUUGACAA A UCUGGAAG
1712
CTTCCAGA GGCTAGCTACAACGA TTGTCAAG
4516





1306
GCAUGGCG A CUGGUAAC
1713
GTTACCAG GGCTAGCTACAACGA CGCCATGC
4517





1313
GACUGGUA A CCGCCUCA
1714
TGAGGCGG GGCTAGCTACAACGA TACCAGTC
4518





1322
CCGCCUCA A UCGACUGA
1715
TCAGTCGA GGCTAGCTACAACGA TGAGGCGG
4519





1326
CUCAAUCG A CUGAAUCA
1716
TGATTCAG GGCTAGCTACAACGA CGATTGAG
4520





1331
UCGACUGA A UCAAGCAG
1717
CTGCTTGA GGCTAGCTACAACGA TCAGTCGA
4521





1360
UGCUGCAG A CAGUUGAG
1718
CTCAACTG GGCTAGCTACAACGA CTGCAGCA
4522





1387
GGGUUGGG A UGGUGACA
1719
TGTCACCA GGCTAGCTACAACGA CCCAACCC
4523





1393
GGAUGGUG A CAUUUGAC
1720
GTCAAATG GGCTAGCTACAACGA CACCATCC
4524





1400
GACAUUUG A CAGUGCUG
1721
CAGCACTG GGCTAGCTACAACGA CAAATGTC
4525





1425
CAAAGUGA A CUCAUACA
1722
TGTATGAG GGCTAGCTACAACGA TCACTTTG
4526





1435
UCAUACAG A UAAACAGU
1723
ACTGTTTA GGCTAGCTACAACGA CTGTATGA
4527





1439
ACAGAUAA A CAGUGGCA
1724
TGCCACTG GGCTAGCTACAACGA TTATCTGT
4528





1451
UGGCAGUG A CAGGGACA
1725
TGTCCCTG GGCTAGCTACAACGA CACTGCCA
4529





1457
UGACAGGG A CACACUCG
1726
CGAGTGTG GGCTAGCTACAACGA CCCTGTCA
4530





1473
GCCAAAAG A UUACCUGC
1727
GCAGGTAA GGCTAGCTACAACGA CTTTTGGC
4531





1498
CAGGAGGG A CGUCCAUC
1728
GATGGACG GGCTAGCTACAACGA CCCTCCTG
4532





1521
GGGCUUCG A UCGGCAUU
1729
AATGCCGA GGCTAGCTACAACGA CGAAGCCC
4533





1537
UUACUGUG A UUAGGAAG
1730
CTTCCTAA GGCTAGCTACAACGA CACAGTAA
4534





1548
AGGAAGAA A UAUCCAAC
1731
GTTGGATA GGCTAGCTACAACGA TTCTTCCT
4535





1555
AAUAUCCA A CUGAUGGA
1732
TCCATCAG GGCTAGCTACAACGA TGGATATT
4536





1559
UCCAACUG A UGGAUCUG
1733
CAGATCCA GGCTAGCTACAACGA CAGTTGGA
4537





1563
ACUGAUGG A UCUGAAAU
1734
ATTTCAGA GGCTAGCTACAACGA CCATCAGT
4538





1570
GAUCUGAA A UUGUGCUG
1735
CAGCACAA GGCTAGCTACAACGA TTCAGATC
4539





1582
UGCUGCUG A CGGAUGGG
1736
CCCATCCG GGCTAGCTACAACGA CAGCAGCA
4540





1586
GCUGACGG A UGGGGAAG
1737
CTTCCCCA GGCTAGCTACAACGA CCGTCAGC
4541





1595
UGGGGAAG A CAACACUA
1738
TAGTGTTG GGCTAGCTACAACGA CTTCCCCA
4542





1598
GGAAGACA A CACUAUAA
1739
TTATAGTG GGCTAGCTACAACGA TGTCTTCC
4543





1619
GUGCUUUA A CGAGGUCA
1740
TGACCTCG GGCTAGCTACAACGA TAAAGCAC
4544





1629
GAGGUCAA A CAAAGUGG
1741
CCACTTTG GGCTAGCTACAACGA TTGACCTC
4545





1683
GCUCAAGA A CUAGAGGA
1742
TCCTCTAG GGCTAGCTACAACGA TCTTGAGC
4546





1702
UGUCCAAA A UGACAGGA
1743
TCCTGTCA GGCTAGCTACAACGA TTTGGACA
4547





1705
CCAAAAUG A CAGGAGGU
1744
ACCTCCTG GGCTAGCTACAACGA CATTTTGG
4548





1720
GUUUACAG A CAUAUGCU
1745
AGCATATG GGCTAGCTACAACGA CTGTAAAC
4549





1733
UGCUUCAG A UCAAGUUC
1746
GAACTTGA GGCTAGCTACAACGA CTGAAGCA
4550





1745
AGUUCAGA A CAAUGGCC
1747
GGCCATTG GGCTAGCTACAACGA TCTGAACT
4551





1748
UCAGAACA A UGGCCUCA
1748
TGAGGCCA GGCTAGCTACAACGA TGTTCTGA
4552





1760
CCUCAUUG A UGCUUUUG
1749
CAAAAGCA GGCTAGCTACAACGA CAATGAGG
4553





1787
AUCAGGAA A UGGAGCUG
1750
CAGCTCCA GGCTAGCTACAACGA TTCCTGAT
4554





1830
AGUAAGGG A UUAACCCU
1751
AGGGTTAA GGCTAGCTACAACGA CCCTTACT
4555





1834
AGGGAUUA A CCCUCCAG
1752
CTGGAGGG GGCTAGCTACAACGA TAATCCCT
4556





1844
CCUCCAGA A CAGCCAGU
1753
ACTGGCTG GGCTAGCTACAACGA TCTGGAGG
4557





1855
GCCAGUGG A UGAAUGGC
1754
GCCATTCA GGCTAGCTACAACGA CCACTGGC
4558





1859
GUGGAUGA A UGGCACAG
1755
CTGTGCCA GGCTAGCTACAACGA TCATCCAC
4559





1870
GCACAGUG A UCGUGGAC
1756
GTCCACGA GGCTAGCTACAACGA CACTGTGC
4560





1877
GAUCGUGG A CAGCACCG
1757
CGGTGCTG GGCTAGCTACAACGA CCACGATC
4561





1895
GGGAAAGG A CACUUUGU
1758
ACAAAGTG GGCTAGCTACAACGA CCTTTCCC
4562





1918
UCACCUGG A CAACGCAG
1759
CTGCGTTG GGCTAGCTACAACGA CCAGGTGA
4563





1921
CCUGGACA A CGCAGCCU
1760
AGGCTGCG GGCTAGCTACAACGA TGTCCAGG
4564





1936
CUCCCCAA A UCCUUCUC
1761
GAGAAGGA GGCTAGCTACAACGA TTGGGGAG
4565





1949
UCUCUGGG A UCCCAGUG
1762
CACTGGGA GGCTAGCTACAACGA CCCAGAGA
4566





1959
CCCAGUGG A CAGAAGCA
1763
TGCTTCTG GGCTAGCTACAACGA CCACTGGG
4567





1985
UGUAGUGG A CAAAAACA
1764
TGTTTTTG GGCTAGCTACAACGA CCACTACA
4568





1991
GGACAAAA A CACCAAAA
1765
TTTTGGTG GGCTAGCTACAACGA TTTTGTCC
4569





1999
ACACCAAA A UGGCCUAC
1766
GTAGGCCA GGCTAGCTACAACGA TTTGGTGT
4570





2014
ACCUCCAA A UCCCAGGC
1767
GCCTGGGA GGCTAGCTACAACGA TTGGAGGT
4571





2046
ACUUGGAA A UACAGUCU
1768
AGACTGTA GGCTAGCTACAACGA TTCCAAGT
4572





2071
GCUCACAA A CCUUGACC
1769
GGTCAAGG GGCTAGCTACAACGA TTGTGAGC
4573





2077
AAACCUUG A CCCUGACU
1770
AGTCAGGG GGCTAGCTACAACGA CAAGGTTT
4574





2083
UGACCCUG A CUGUCACG
1771
CGTGACAG GGCTAGCTACAACGA CAGGGTCA
4575





2105
UGCGUCCA A UGCUACCC
1772
GGGTAGCA GGCTAGCTACAACGA TGGACGCA
4576





2122
UGCCUCCA A UUACAGUG
1773
CACTGTAA GGCTAGCTACAACGA TGGAGGCA
4577





2131
UUACAGUG A CUUCCAAA
1774
TTTGGAAG GGCTAGCTACAACGA CACTGTAA
4578





2140
CUUCCAAA A CGAACAAG
1775
CTTGTTCG GGCTAGCTACAACGA TTTGGAAG
4579





2144
CAAAACGA A CAAGGACA
1776
TGTCCTTG GGCTAGCTACAACGA TCGTTTTG
4580





2150
GAACAAGG A CACCAGCA
1777
TGCTGGTG GGCTAGCTACAACGA CCTTGTTC
4581





2160
ACCAGCAA A UUCCCCAG
1778
CTGGGGAA GGCTAGCTACAACGA TTGCTGGT
4582





2189
UUAUGCAA A UAUUCGCC
1779
GGCGAATA GGCTAGCTACAACGA TTGCATAA
4583





2212
CCUCCCCA A UUCUCAGG
1780
CCTGAGAA GGCTAGCTACAACGA TGGGGAGG
4584





2239
CAGCCCUG A UUGAAUCA
1781
TGATTCAA GGCTAGCTACAACGA CAGGGCTG
4585





2244
CUGAUUGA A UCAGUGAA
1782
TTCACTGA GGCTAGCTACAACGA TCAATCAG
4586





2252
AUCAGUGA A UGGAAAAA
1783
TTTTTCCA GGCTAGCTACAACGA TCACTGAT
4587





2260
AUGGAAAA A CAGUUACC
1784
GGTAACTG GGCTAGCTACAACGA TTTTCCAT
4588





2274
ACCUUGGA A CUACUGGA
1785
TCCAGTAG GGCTAGCTACAACGA TCCAAGGT
4589





2282
ACUACUGG A UAAUGGAG
1786
CTCCATTA GGCTAGCTACAACGA CCAGTAGT
4590





2285
ACUGGAUA A UGGAGCAG
1787
CTGCTCCA GGCTAGCTACAACGA TATCCAGT
4591





2300
AGGUGCUG A UGCUACUA
1788
TAGTAGCA GGCTAGCTACAACGA CAGCACCT
4592





2312
UACUAAGG A UGACGGUG
1789
CACCGTCA GGCTAGCTACAACGA CCTTAGTA
4593





2315
UAAGGAUG A CGGUGUCU
1790
AGACACCG GGCTAGCTACAACGA CATCCTTA
4594





2341
AUUUCACA A CUUAUGAC
1791
GTCATAAG GGCTAGCTACAACGA TGTGAAAT
4595





2348
AACUUAUG A CACGAAUG
1792
CATTCGTG GGCTAGCTACAACGA CATAAGTT
4596





2354
UGACACCA A UGGUAGAU
1793
ATCTACCA GGCTAGCTACAACGA TCGTGTCA
4597





2361
AAUGGUAG A UACAGUGU
1794
ACACTGTA GGCTAGCTACAACGA CTACCATT
4598





2396
AGGAGUUA A CGCAGCCA
1795
TGGCTGCG GGCTAGCTACAACGA TAACTCCT
4599





2406
GCAGCCAG A CGGAGAGU
1796
ACTCTCCG GGCTAGCTACAACGA CTGGCTGC
4600





2416
GGAGAGUG A UACCCCAG
1797
CTGGGGTA GGCTAGCTACAACGA CACTCTCC
4601





2455
CUGGCUGG A UUGAGAAU
1798
ATTCTCAA GGCTAGCTACAACGA CCAGCCAG
4602





2462
GAUUGAGA A UGAUGAAA
1799
TTTCATCA GGCTAGCTACAACGA TCTCAATC
4603





2465
UGAGAAUG A UGAAAUAC
1800
GTATTTCA GGCTAGCTACAACGA CATTCTCA
4604





2470
AUGAUGA A AUCAAUGG
1801
CCATTGTA GGCTAGCTACAACGA TTCATCAT
4605





2475
GAAAUACA A UGGAAUCC
1802
GGATTCCA GGCTAGCTACAACGA TGTATTTC
4606





2480
ACAAUGGA A UCCACCAA
1803
TTGGTGGA GGCTAGCTACAACGA TCCATTGT
4607





2490
CCACCAAG A CCUGAAAU
1804
ATTTCAGG GGCTAGCTACAACGA CTTGGTGG
4608





2497
GACCUGAA A UUAAUAAG
1805
CTTATTAA GGCTAGCTACAACGA TTCAGGTC
4609





2501
UGAAAUUA A UAAGGAUG
1806
CATCCTTA GGCTAGCTACAACGA TAATTTCA
4610





2507
UAAUAAGG A UGAUGUUC
1807
GAACATCA GGCTAGCTACAACGA CCTTATTA
4611





2510
UAAGGAUG A UGUUCAAC
1808
GTTGAACA GGCTAGCTACAACGA CATCCTTA
4612





2517
GAUGUUCA A CACAAGCA
1809
TGCTTGTG GGCTAGCTACAACGA TGAACATC
4613





2542
UCAGCAGA A CAUCCUCG
1810
CGAGGATG GGCTAGCTACAACGA TCTGCTGA
4614





2573
GGCUUCUG A UGUCCCAA
1811
TTGGGACA GGCTAGCTACAACGA CAGAAGCC
4615





2582
UGUCCCAA A UGCUCCCA
1812
TGGGAGCA GGCTAGCTACAACGA TTGGGACA
4616





2597
CAUACCUG A UCUCUUCC
1813
GGAAGAGA GGCTAGCTACAACGA CAGGTATG
4617





2617
CUGGCCAA A UCACCGAC
1814
GTCGGTGA GGCTAGCTACAACGA TTGGCCAG
4618





2624
AAUCACCG A CCUGAAGG
1815
CCTTCAGG GGCTAGCTACAACGA CGGTGATT
4619





2638
AGGCGGAA A UUCACGGG
1816
CCCGTGAA GGCTAGCTACAACGA TTCCGCCT
4620





2660
UCUCAUUA A UCUGACUU
1817
AAGTCAGA GGCTAGCTACAACGA TAATGAGA
4621





2665
UUAAUCUG A CUUGGACA
1818
TGTCCAAG GGCTAGCTACAACGA CAGATTAA
4622





2671
UGACUUGG A CAGCUCCU
1819
AGGAGCTG GGCTAGCTACAACGA CCAAGTCA
4623





2684
UCCUGGGG A UGAUUAUG
1820
CATAATCA GGCTAGCTACAACGA CCCCAGGA
4624





2687
UGGGGAUG A UUAUGACC
1821
GGTCATAA GGCTAGCTACAACGA CATCCCCA
4625





2693
UGAUUAUG A CCAUGGAA
1822
TTCCATGG GGCTAGCTACAACGA CATAATCA
4626





2701
ACCAUGGA A CAGCUCAC
1823
GTGAGCTG GGCTAGCTACAACGA TCCATGGT
4627





2725
UCAUUCGA A UAAGUACA
1824
TGTACTTA GGCTAGCTACAACGA TCGAATGA
4628





2744
UAUUCUUG A UCUCAGAG
1825
CTCTGAGA GGCTAGCTACAACGA CAAGAATA
4629





2753
UCUCAGAG A CAAGUUCA
1826
TGAACTTG GGCTAGCTACAACGA CTCTGAGA
4630





2762
CAAGUUCA A UGAAUCUC
1827
GAGATTCA GGCTAGCTACAACGA TGAACTTG
4631





2766
UUCAAUGA A UCUCUUCA
1828
TGAAGAGA GGCTAGCTACAACGA TCATTGAA
4632





2780
UCAAGUGA A UACUACUG
1829
CAGTAGTA GGCTAGCTACAACGA TCACTTGA
4633





2810
GGAAGCCA A CUCUGAGG
1830
CCTCAGAG GGCTAGCTACAACGA TGGCTTCC
4634





2835
UUGUUUAA A CCAGAAAA
1831
TTTTCTGG GGCTAGCTACAACGA TTAAACAA
4635





2843
ACCAGAAA A CAUUACUU
1832
AAGTAATG GGCTAGCTACAACGA TTTCTGGT
4636





2858
UUUUGAAA A UGGCACAG
1833
CTGTGCCA GGCTAGCTACAACGA TTTCAAAA
4637





2867
UGGCACAG A UCUUUUCA
1834
TGAAAAGA GGCTAGCTACAACGA CTGTGCCA
4638





2894
GGCUGUUG A UAAGGUCG
1835
CGACCTTA GGCTAGCTACAACGA CAACAGCC
4639





2903
UAAGGUCG A UCUGAAAU
1836
ATTTCAGA GGCTAGCTACAACGA CGACCTTA
4640





2910
GAUCUGAA A UCAGAAAU
1837
ATTTCTGA GGCTAGCTACAACGA TTCAGATC
4641





2917
AAUCAGAA A UAUCCAAC
1838
GTTGGATA GGCTAGCTACAACGA TTCTGATT
4642





2924
AAUAUCCA A CAUUGCAC
1839
GTGCAATG GGCTAGCTACAACGA TGGATATT
4643





2959
CUCCACAG A CUCCGCCA
1840
TGGCGGAG GGCTAGCTACAACGA CTGTGGAG
4644





2971
CGCCAGAG A CACCUAGU
1841
ACTAGGTG GGCTAGCTACAACGA CTCTGGCG
4645





2984
UAGUCCUG A UGAAACGU
1842
ACGTTTCA GGCTAGCTACAACGA CAGGACTA
4646





2989
CUGAUGAA A CGUCUGCU
1843
AGCAGACG GGCTAGCTACAACGA TTCATCAG
4647





3008
UUGUCCUA A UAUUCAUA
1844
TATGAATA GGCTAGCTACAACGA TAGGACAA
4648





3020
UCAUAUCA A CAGCACCA
1845
TGGTGCTG GGCTAGCTACAACGA TGATATGA
4649





3052
UUUUAAAA A UUAUGUGG
1846
CCACATAA GGCTAGCTACAACGA TTTTAAAA
4650





3067
GGAAGUGG A UAGGAGAA
1847
TTCTCCTA GGCTAGCTACAACGA CCACTTCC
4651





3075
AUAGGAGA A CUGCAGCU
1848
AGCTGCAG GGCTAGCTACAACGA TCTCCTAT
4652





3088
AGCUGUCA A UAGCCUAG
1849
CTAGGCTA GGCTAGCTACAACGA TGACAGCT
4653





3103
AGGGCUGA A UUUUUGUC
1850
GACAAAAA GGCTAGCTACAACGA TCAGCCCT
4654





3114
UUUGUCAG A UAAAUAAA
1851
TTTATTTA GGCTAGCTACAACGA CTGACAAA
4655





3118
UCAGAUAA A UAAAAUAA
1852
TTATTTTA GGCTAGCTACAACGA TTATCTGA
4656





3123
UAAAUAAA A UAAAUCAU
1853
ATGATTTA GGCTAGCTACAACGA TTTATTTA
4657





3127
UAAAAUAA A UCAUUCAU
1854
ATGAATGA GGCTAGCTACAACGA TTATTTTA
4658





3146
UUUUUUUG A UUAUAAAA
1855
TTTTATAA GGCTAGCTACAACGA CAAAAAAA
4659





3154
AUUAUAAA A UUUUCUAA
1856
TTAGAAAA GGCTAGCTACAACGA TTTATAAT
4660





3164
UUUCUAAA A UGUAUUUU
1857
AAAATACA GGCTAGCTACAACGA TTTAGAAA
4661





3175
UAUUUUAG A CUUCCUGU
1858
ACAGGAAG GGCTAGCTACAACGA CTAAAATA
4662





3265
UAUUUUAG A CUUCCUGU
1858
ACAGGAAG GGCTAGCTACAACGA CTAAAATA
4662





3192
AGGGGGCG A UAUACUAA
1859
TTAGTATA GGCTAGCTACAACGA CGCCCCCT
4663





3245
AGGGGGCG A UAUACUAA
1859
TTAGTATA GGCTAGCTACAACGA CGCCCCCT
4663





3201
UAUACUAA A UGUAUAUA
1860
TATATACA GGCTAGCTACAACGA TTAGTATA
4664





3225
UAUACUAA A UGUAUUCC
1861
GGAATACA GCCTAGCTACAACGA TTAGTATA
4665





3254
UAUACUAA A UGUAUUUU
1862
AAAATACA GGCTAGCTACAACGA TTAGTATA
4666





3282
AGGGGGCG A UAAAAUAA
1863
TTATTTTA GGCTAGCTACAACGA CGCCCCCT
4667





3287
GCGAUAAA A UAAAAUGC
1864
GCATTTTA GGCTAGCTACAACGA TTTATCGC
4668





3292
AAAAUAAA A UGCUAAAC
1865
GTTTAGCA GGCTAGCTACAACGA TTTATTTT
4669





3299
AAUGCUAA A CAACUGGG
1866
CCCAGTTG GGCTAGCTACAACGA TTAGCATT
4670





3302
GCUAAACA A CUGGGUAA
1867
TTACCCAG GGCTAGCTACAACGA TGTTTAGC
4671






Input Sequence = NM_001285. Cut Site = R/Y




Arm Length = 8. Core Sequence = GGCTAGCTACAACGA




NM_001285 (Homo sapiens chloride channel, calcium activated, 1 (CLCA1) mRNA, 3311 bp)








[0195]

8







TABLE VIII













Human CLCA1 Amberzyme and Target Sequence 249.021















Rz




Seq

Seq




ID

ID


Pos
Substrate
No.
Amberzyme
No.














40
AUAUAAUU G AAUAUUUU
1211
AAAAUAUU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AAUUAUAU
4672





67
GGGAGCAU G AAGAGGUG
1212
CACCUCUU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AUGCUCCC
4673





78
GAGGUGUU G AGGUUAUG
1213
CAUAACCU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AACACCUC
4674





106
GCACAGCU G AAGGCAGA
1214
UCUGCCUU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AGCUGUGC
4675





134
ACAAGUAC G CAAUUUGA
1215
UCAAAUUG GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG GUACUUGU
4676





141
CGCAAUUU G AGACUAAG
1216
CUUAGUCU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AAAUUGCG
4677





172
CUCCUAUU G AAGACAAG
1217
CUUGUCUU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AAUAGGAG
4678





223
AGACCUGU G AUAAACCA
1218
UGGUUUAU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG ACAGGUCU
4679





237
CCACUUCC G AUAAGUUG
1219
CAACUUAU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG GGAAGUGG
4680





312
CGUAACCC G CAUUUUCC
1220
GGAAAAUG GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG GGGUUACG
4681





384
UUCAUCUU G AUUCUUCA
1221
UGAAGAAU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AAGAUGAA
4682





411
GGGGCCCU G AGUAAUUC
1222
GAAUUACU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AGGGCCCC
4683





432
AUUCAGCU G AACAACAA
1223
UUGUUGUU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AGCUGAAU
4684





448
AUGGCUAU G AAGGCAUU
1224
AAUGCCUU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AUAGCCAU
4685





463
UUGUCGUU G CAAUCGAC
1225
GUCGAUUG GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AACGACAA
4686





469
UUGCAAUC G ACCCCAAU
1226
AUUGGGGU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG GAUUGCAA
4687





480
CCCAAUGU G CCAGAAGA
1227
UCUUCUGG GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG ACAUUGGG
4688





490
CAGAAGAU G AAACACUC
1228
GAGUGUUU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AUCUUCUG
4689





522
GACAUGGU G ACCCAGGC
1229
GCCUGGGU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG ACCAUGUC
4690





547
AUCUGUUU G AAGCUACA
1230
UGUAGCUU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AAACAGAU
4691





563
AGGAAAGC G AUUUUAUU
1231
AAUAAAAU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG GCUUUCCU
4692





583
AAAAUGUU G CCAUUUUG
1232
CAAAAUGG GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AACAUUUU
4693





591
GCCAUUUU G AUUCCUGA
1233
UCAGGAAU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AAAAUGGC
4694





598
UGAUUCCU G AAACAUGG
1234
CCAUGUUU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AGGAAUCA
4695





619
CAAAGGCU G ACUAUGUG
1235
CACAUAGU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AGCCUUUG
4696





627
GACUAUGU G AGACCAAA
1236
UUUGGUCU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG ACAUAGUC
4697





640
CAAAACUU G AGACCUAC
1237
GUAGGUCU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AAGUUUUG
4698





655
ACAAAAAU G CUGAUGUU
1238
AACAUCAG GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AUUUUUGU
4699





658
AAAAUGCU G AUGUUCUG
1239
CAGAACAU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AGCAUUUU
4700





670
UUCUGGUU G CUGAGUCU
1240
AGACUCAG GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AACCAGAA
4701





673
UGGUUGCU G AGUCUACU
1241
AGUAGACU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AGCAACCA
4702





694
CAGGUAAU G AUGAACCC
1242
GGGUUCAU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AUUACCUG
4703





697
GUAAUGAU G AACCCUAC
1243
GUAGGGUU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AUCAUUAC
4704





709
CCUACACU G AGCAGAUG
1244
CAUCUGCU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AGUGUAGG
4705





739
AGAAGGGU G AAAGGAUC
1245
GAUCCUUU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG ACCCUUCU
4706





760
UCACUCCU G AUUUCAUU
1246
AAUGAAAU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AGGAGUGA
4707





769
AUUUCAUU G CAGGAAAA
1247
UUUUCCUG GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AAUGAAAU
4708





787
AGUUAGCU G AAUAUGGA
1248
UCCAUAUU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AGCUAACU
4709





820
UUGUCCAU G AGUGGGCU
1249
AGCCCACU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AUGGACAA
4710





836
UCAUCUAC G AUGGGGAG
1250
CUCCCCAU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG GUAGAUGA
4711





850
GAGUAUUU G ACGAGUAC
1251
GUACUCGU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AAAUACUC
4712





853
UAUUUGAC G AGUACAAU
1252
AUUGUACU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG GUCAAAUA
4713





865
ACAAUAAU G AUGAGAAA
1253
UUUCUCAU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AUUAUUGU
4714





868
AUAAUGAU G AGAAAUUC
1254
GAAUUUCU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AUCAUUAU
4715





980
CAAAAGAU G CACAUUCA
1255
UGAAUGUG GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AUCUUUUG
4716





1009
GACUCUAU G AAAAAGGA
1256
UCCUUUUU GGA GCCGUGAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AUAGAGUC
4717





1021
AAGGAUGU G AGUUUGUU
1257
AACAAACU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG ACAUCCUU
4718





1040
CCAAUCCC G CCAGACGG
1258
CCGUCUGG GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG GGGAUUGG
4719





1069
UAAUGUUU G CACAACAU
1259
AUGUUGUG GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AAACAUUA
4720





1081
AACAUGUU G AUUCUAUA
1260
UAUAGAAU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AACAUGUU
4721





1093
CUAUAGUU G AAUUCUGU
1261
ACAGAAUU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AACUAUAG
4722





1151
UCAAAAAU G CAAUCUCC
1262
GGAGAUUG GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AUUUUUGA
4723





1160
CAAUCUCC G AAGCACAU
1263
AUGUGCUU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG GGAGAUUG
4724





1176
UGGGAAGU G AUCCGUGA
1264
UCACGGAU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG ACUUCCCA
4725





1183
UGAUCCGU G AUUCUGAG
1265
CUCAGAAU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG ACGGAUCA
4726





1189
GUGAUUCU G AGGACUUU
1266
AAAGUCCU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AGAAUCAC
4727





1215
ACUCCUAU G ACAACACA
1267
UGUGUUGU GGA GCCGUGAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AUAGGAGU
4728





1248
UUCUCAUU G CUGCAGAU
1268
AUCUGCAG GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AAUGAGAA
4729





1251
UCAUUGCU G CAGAUUGG
1269
CCAAUCUG GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AGCAAUGA
4730





1285
UACUCCUU G ACAAAUCU
1270
AGAUUUGU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AAGGACUA
4731





1305
AGCAUGGC G ACUGGUAA
1271
UUACCAGU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG GCCAUGCU
4732





1316
UGGUAACC G CCUCAAUC
1272
GAUUGAGG GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG GGUUACCA
4733





1325
CCUCAAUC G ACUGAAUC
1273
GAUUCAGU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG GAUUGAGG
4734





1329
AAUCGACU G AAUCAAGC
1274
GCUUGAUU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AGUCGAUU
4735





1353
CUUUUCCU G CUGCAGAC
1275
GUCUGCAG GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AGGAAAAG
4736





1356
UUCCUGCU G CAGACAGU
1276
ACUGUCUG GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AGCAGGAA
4737





1366
AGACAGUU G AGCUGGGG
1277
CCCCAGCU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AACUGUCU
4738





1392
GGGAUGGU G ACAUUUGA
1278
UCAAAUGU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG ACCAUCCC
4739





1399
UGACAUUU G ACAGUGCU
1279
AGCACUGU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AAAUGUCA
4740





1405
UUGACAGU G CUGCCCAU
1280
AUGGGCAG GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG ACUGUCAA
4741





1408
ACAGUGCU G CCCAUGUA
1281
UACAUGGG GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AGCACUGU
4742





1423
UACAAAGU G AACUCAUA
1282
UAUGAGUU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG ACUUUGUA
4743





1450
GUGGCAGU G ACAGGGAC
1283
GUCCCUGU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG ACUGCCAC
4744





1465
ACACACUC G CCAAAAGA
1284
UCUUUUGG GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG GAGUGUGU
4745





1480
GAUUACCU G CAGCAGCU
1285
AGCUGCUG GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AGGUAAUC
4746





1508
GUCCAUCU G CAGCGGGC
1286
GCCCGCUG GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AGAUGGAC
4747





1520
CGGGCUUC G AUCGGCAU
1287
AUGCCGAU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG GAAGCCCG
4748





1536
UUUACUGU G AUUAGGAA
1288
UUCCUAAU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG ACAGUAAA
4749





1558
AUCCAACU G AUGGAUCU
1289
AGAUCCAU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AGUUGGAU
4750





1567
AUGGAUCU G AAAUUGUG
1290
CACAAUUU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AGAUCCAU
4751





1575
GAAAUUGU G CUGCUGAC
1291
GUCAGCAG GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG ACAAUUUC
4752





1578
AUUGUGCU G CUGACGGA
1292
UCCGUCAG GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AGCACAAU
4753





1581
GUGCUGCU G ACGGAUGG
1293
CCAUCCGU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AGCAGCAC
4754





1613
AAGUGGGU G CUUUAACG
1294
CGUUAAAG GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG ACCCACUU
4755





1621
GCUUUAAC G AGGUCAAA
1295
UUUGACCU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG GUUAAAGC
4756





1639
AAAGUGGU G CCAUCAUC
1296
GAUGAUGG GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG ACCACUUU
4757





1657
ACACAGUC G CUUUGGGG
1297
CCCCAAAG GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG GACUGUGU
4758





1672
GGCCCUCU G CAGCUCAA
1298
UUGAGCUG GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AGAGGGCC
4759





1704
UCCAAAAU G ACAGGAGG
1299
CCUCCUGU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AUUUUGGA
4760





1726
AGACAUAU G CUUCAGAU
1300
AUCUGAAG GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AUAUGUCU
4761





1759
GCCUCAUU G AUGCUUUU
1301
AAAAGCAU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AAUGAGGC
4762





1762
UCAUUGAU G CUUUUGGG
1302
CCCAAAAG GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AUCAAUGA
4763





1805
CUCUCAGC G CUCCAUCC
1303
GGAUGGAG GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG GCUGAGAG
4764





1819
UCCAGCUU G AGAGUAAG
1304
CUUACUCU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AAGCUGGA
4765





1857
CAGUGGAU G AAUGGCAC
1305
GUGCCAUU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AUCCACUG
4766





1869
GGCACAGU G AUCGUGGA
1306
UCCACGAU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG ACUGUGCC
4767





1923
UGGACAAC G CAGCCUCC
1307
GGAGGCUG GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG GUUGUCCA
4768





2026
CAGGCAUU G CUAAGGUU
1308
AACCUUAG GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AAUGCCUG
4769





2055
UACAGUCU G CAAGCAAG
1309
CUUGCUUG GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AGACUGUA
4770





2076
CAAACCUU G ACCCUGAC
1310
GUCAGGGU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AAGGUUUG
4771





2082
UUGACCCU G ACUGUCAC
1311
GUGACAGU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AGGGUCAA
4772





2098
CGUCCCGU G CGUCCAAU
1312
AUUGGACG GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG ACGGGACG
4773





2107
CGUCCAAU G CUACCCUG
1313
CAGGGUAG GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AUUGGACG
4774





2115
GCUACCCU G CCUCCAAU
1314
AUUGGAGG GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AGGGUAGC
4775





2130
AUUACAGU G ACUUCCAA
1315
UUGGAAGU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG ACUGUAAU
4776





2142
UCCAAAAC G AACAAGGA
1316
UCCUUGUU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG GUUUUGGA
4777





2185
UAGUUUAU G CAAAUAUU
1317
AAUAUUUG GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AUAAACUA
4778





2195
AAAUAUUC G CCAAGGAG
1318
CUCCUUGG GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG GAAUAUUU
4779





2238
ACAGCCCU G AUUGAAUC
1319
GAUUCAAU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AGGGCUGU
4780





2242
CCCUGAUU G AAUCAGUG
1320
CACUGAUU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AAUCAGGG
4781





2250
GAAUCAGU G AAUGGAAA
1321
UUUCCAUU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG ACUGAUUC
4782





2296
GAGCAGGU G CUGAUGCU
1322
AGCAUCAG GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG ACCUGCUC
4783





2299
CAGGUGCU G AUGCUACU
1323
AGUAGCAU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AGCACCUG
4784





2302
GUGCUGAU G CUACUAAG
1324
CUUAGUAG GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AUCAGCAC
4785





2314
CUAAGGAU G ACGGUGUC
1325
GACACCGU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AUCCUUAG
4786





2347
CAACUUAU G ACACGAAU
1326
AUUCGUGU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AUAAGUUG
4787





2352
UAUGACAC G AAUGGUAG
1327
CUACCAUU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG GUGUCAUA
4788





2376
GUAAAAGU G CGGGCUCU
1328
AGAGCCCG GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG ACUUUUAC
4789





2398
GAGUUAAC G CAGCCAGA
1329
UCUGGCUG GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG GUUAACUC
4790





2415
CGGAGAGU G AUACCCCA
1330
UGGGGUAU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG ACUCUCCG
4791





2458
GCUGGAUU G AGAAUGAU
1331
AUCAUUCU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AAUCCAGC
4792





2464
UUGAGAAU G AUGAAAUA
1332
UAUUUCAU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AUUCUCAA
4793





2467
AGAAUGAU G AAAUACAA
1333
UUGUAUUU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AUCAUUCU
4794





2494
CAAGACCU G AAAUUAAU
1334
AUUAAUUU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AGGUCUUG
4795





2509
AUAAGGAU G AUGUUCAA
1335
UUGAACAU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AUCCUUAU
4796





2572
UGGCUUCU G AUGUCCCA
1336
UGGGACAU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AGAAGCCA
4797





2584
UCCCAAAU G CUCCCAUA
1337
UAUGGGAG GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AUUUGGGA
4798





2596
CCAUACCU G AUCUCUUC
1338
GAAGAGAU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AGGUAUGG
4799





2623
AAAUCACC G ACCUGAAG
1339
CUUCAGGU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG GGUGAUUU
4800





2628
ACCGACCU G AAGGCGGA
1340
UCCGCCUU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AGGUCGGU
4801





2664
AUUAAUCU G ACUUGGAC
1341
GUCCAAGU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AGAUUAAU
4802





2686
CUGGGGAU G AUUAUGAC
1342
GUCAUAAU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AUCCCCAG
4803





2692
AUGAUUAU G ACCAUGGA
1343
UCCAUGGU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AUAAUCAU
4804





2723
UAUCAUUC G AAUAAGUA
1344
UACUUAUU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG GAAUGAUA
4805





2743
GUAUUCUU G AUCUCAGA
1345
UCUGAGAU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AAGAAUAC
4806





2764
AGUUCAAU G AAUCUCUU
1346
AAGAGAUU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AUUGAACU
4807





2778
CUUCAAGU G AAUACUAC
1347
GUAGUAUU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG ACUUGAAG
4808





2788
AUACUACU G CUCUCAUC
1348
GAUGAGAG GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AGUAGUAU
4809





2815
CCAACUCU G AGGAAGUC
1349
GACUUCCU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AGAGUUGG
4810





2854
UUACUUUU G AAAAUGGC
1350
GCCAUUUU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AAAAGUAA
4811





2878
UUUUCAUU G CUAUUCAG
1351
CUGAAUAG GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AAUGAAAA
4812





2893
AGGCUGUU G AUAAGGUC
1352
GACCUUAU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AACAGCCU
4813





2902
AUAAGGUC G AUCUGAAA
1353
UUUCAGAU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG GACCUUAU
4814





2907
GUCGAUCU G AAAUCAGA
1354
UCUGAUUU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AGAUCGAC
4815





2929
CCAACAUU G CACGAGUA
1355
UACUCGUG GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AAUGUUGG
4816





2933
CAUUGCAC G AGUAUCUU
1356
AAGAUACU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG GUGCAAUG
4817





2964
CAGACUCC G CCAGAGAC
1357
GUCUCUGG GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG GGAGUCUG
4818





2983
CUAGUCCU G AUGAAACG
1358
CGUUUCAU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AGGACUAG
4819





2986
GUCCUGAU G AAACGUCU
1359
AGACGUUU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AUCAGGAC
4820





2995
AAACGUCU G CUCCUUGU
1360
ACAAGGAG GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AGACGUUU
4821





3078
GGAGAACU G CAGCUGUC
1361
GACAGCUG GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AGUUCUCC
4822





3101
CUAGGGCU G AAUUUUUG
1362
CAAAAAUU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AGCCCUAG
4823





3145
CUUUUUUU G AUUAUAAA
1363
UUUAUAAU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AAAAAAAG
4824





3191
UAGGGGGC G AUAUACUA
1364
UAGUAUAU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG GCCCCCUA
4825





3244
UAGGGGGC G AUAUACUA
1364
UAGUAUAU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG GCCCCCUA
4825





3281
UAGGGGGC G AUAAAAUA
1365
UAUUUUAU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG GCCCCCUA
4826





3294
AAUAAAAU G CUAAACAA
1366
UUGUUUAG GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AUUUUAUU
4827





27
AAAUGGAU G UGGAAUAU
1367
AUAUUCCA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AUCCAUUU
4828





52
AUUUUCUU G UUUAAGGG
1368
CCCUUAAA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AAGAAAAU
4829





75
GAAGAGGU G UUGAGGUU
1369
AACCUCAA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG ACCUCUUC
4830





86
GAGGUUAU G UCAAGCAU
1370
AUGCUUGA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AUAACCUC
4831





155
AAGAUAUU G UUAUCAUU
1371
AAUGAUAA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AAUAUCUU
4832





221
AAAGACCU G UGAUAAAC
1372
GUUUAUCA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AGGUCUUU
4833





253
GGAAACGU G UGUCUAUA
1373
UAUAGACA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG ACGUUUCC
4834





255
AAACGUGU G UCUAUAUU
1374
AAUAUAGA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG ACACGUUU
4835





273
UCAUAUCU G UAUAUAUA
1375
UAUAUAUA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AGAUAUGA
4836





344
AGGGAGAU G UACAGCAA
1376
UUGCUGUA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AUCUCCCU
4837





373
AGAGUUCU G UGUUCAUC
1377
GAUGAACA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AGAACUCU
4838





375
AGUUCUGU G UUCAUCUU
1378
AAGAUGAA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG ACAGAACU
4839





457
AAGGCAUU G UCGUUGCA
1379
UGCAACGA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AAUGCCUU
4840





478
ACCCCAAU G UGCCAGAA
1380
UUCUGGCA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AUUGGGGU
4841





537
GCAUCUCU G UAUCUGUU
1381
AACAGAUA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AGAGAUGC
4842





543
CUGUAUCU G UUUGAAGC
1382
GCUUCAAA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AGAUACAG
4843





580
UCAAAAAU G UUGCCAUU
1383
AAUGGCAA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AUUUUUGA
4844





625
CUGACUAU G UGAGACCA
1384
UGGUCUCA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AUAGUCAG
4845





661
AUGCUGAU G UUCUGGUU
1385
AACCAGAA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AUCAGCAU
4846





725
GGGCAACU G UGGAGAGA
1386
UCUCUCCA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AGUUGCCC
4847





814
AGGCAUUU G UCCAUGAG
1387
CUCAUGGA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AAAUGCCU
4848





911
AGUAAGAU G UUCAGCAG
1388
CUGCUGAA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AUCUUACU
4849





937
GUACAAAU G UAGUAAAG
1389
CUUUACUA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AUUUGUAC
4850





950
AAAGAAGU G UCAGGGAG
1390
CUCCCUGA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG ACUUCUUU
4851





965
AGGCAGCU G UUACACCA
1391
UGGUGUAA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AGCUGCCU
4852





1019
AAAAGGAU G UGAGUUUG
1392
CAAACUCA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AUCCUUUU
4853





1027
GUGAGUUU G UUCUCCAA
1393
UUGGAGAA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AAACUCAC
4854





1065
UCUAUAAU G UUUGCACA
1394
UGUGCAAA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AUUAUAGA
4855





1078
CACAACAU G UUGAUUCU
1395
AGAAUCAA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AUGUUGUG
4856





1100
UGAAUUCU G UACAGAAC
1396
GUUCUGUA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AGAAUUCA
4857





1270
AAAGAAUU G UGUGUUUA
1397
UAAACACA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AAUUCUUU
4858





1272
AGAAUUGU G UGUUUAGU
1398
ACUAAACA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG ACAAUUCU
4859





1274
AAUUGUGU G UUUAGUCC
1399
GGACUAAA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG ACACAAUU
4860





1414
CUGCCCAU G UACAAAGU
1400
ACUUUGUA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AUGGGCAG
4861





1534
CAUUUACU G UGAUUAGG
1401
CCUAAUCA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AGUAAAUG
4862





1573
CUGAAAUU G UGCUGCUG
1402
CAGCAGCA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AAUUUCAG
4863





1695
GAGGAGCU G UCCAAAAU
1403
AUUUUGGA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AGCUCCUC
4864





1795
AUGGAGCU G UCUCUCAG
1404
CUGAGAGA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AGCUCCAU
4865





1902
GACACUUU G UUUCUUAU
1405
AUAAGAAA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AAAGUGUC
4866





1978
GUGGCUUU G UAGUGGAC
1406
GUCCACUA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AAAGCCAC
4867





2086
CCCUGACU G UCACGUCC
1407
GGACGUGA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AGUCAGGG
4868





2227
GGGCCAGU G UCACAGCC
1408
GGCUGUGA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG ACUGGCCC
4869





2320
AUGACGGU G UCUACUCA
1409
UGAGUAGA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG ACCGUCAU
4870





2368
GAUACAGU G UAAAAGUG
1410
CACUUUUA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG ACUGUAUC
4871





2439
GGAGCACU G UACAUACC
1411
GGUAUGUA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AGUGCUCC
4872





2512
AGGAUGAU G UUCAACAC
1412
GUGUUGAA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AUCAUCCU
4873





2529
AAGCAAGU G UGUUUCAG
1413
CUGAAACA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG ACUUGCUU
4874





2531
GCAAGUGU G UUUCAGCA
1414
UGCUGAAA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG ACACUUGC
4875





2563
GCUCAUUU G UGGCUUCU
1415
AGAAGCCA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AAAUGAGC
4876





2575
CUUCUGAU G UCCCAAAU
1416
AUUUGGGA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AUCAGAAG
4877





2829
GUCUUUUU G UUUAAACC
1417
GGUUUAAA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AAAAAGAC
4878





2890
UUCAGGCU G UUGAUAAG
1418
CUUAUCAA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AGCCUGAA
4879





2943
GUAUCUUU G UUUAUUCC
1419
GGAAUAAA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AAAGAUAC
4880





3002
UGCUCCUU G UCCUAAUA
1420
UAUUAGGA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AAGGAGCA
4881





3057
AAAAUUAU G UGGAAGUG
1421
CACUUCCA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AUAAUUUU
4882





3084
CUGCAGCU G UCAAUAGC
1422
GCUAUUGA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AGCUGCAG
4883





3109
GAAUUUUU G UCAGAUAA
1423
UUAUCUGA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AAAAAUUC
4884





3166
UCUAAAAU G UAUUUUAG
1424
CUAAAAUA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AUUUUAGA
4885





3182
GACUUCCU G UAGGGGGC
1425
GCCCCCUA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AGGAAGUC
4886





3272
GACUUCCU G UAGGGGGC
1425
GCCCCCUA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AGGAAGUC
4886





3203
UACUAAAU G UAUAUAGU
1426
ACUAUAUA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AUUUAGUA
4887





3227
UACUAAAU G UAUUCCUG
1427
CAGGAAUA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AUUUAGUA
4888





3235
GUAUUCCU G UAGGGGGC
1428
GCCCCCUA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AGGAAUAC
4889





3256
UACUAAAU G UAUUUUAG
1429
CUAAAAUA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AUUUAGUA
4890





15
UGCUUUUG G UACAAAUG
1430
CAUUUGUA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CAAAAGCA
4891





63
UAAGGGGA G CAUGAAGA
1431
UCUUCAUG GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UCCCCUUA
4892





73
AUGAAGAG G UGUUGAGG
1432
CCUCAACA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CUCUUCAU
4893





81
GUGUUGAG G UUAUGUCA
1433
UGACAUAA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CUCAACAC
4894





91
UAUGUCAA G CAUCUGGC
1434
GCCAGAUG GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UUGACAUA
4895





98
AGCAUCUG G CACAGCUG
1435
CAGCUGUG GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CAGAUGCU
4896





103
CUGGCACA G CUGAAGGC
1436
GCCUUCAG GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UGUGCCAG
4897





110
AGCUGAAG G CAGAUGGA
1437
UCCAUCUG GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CUUCAGCU
4898





130
AUUUACAA G UACGCAAU
1438
AUUGCGUA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UUGUAAAU
4899





182
AGACAAGA G CAAUAGUA
1439
UACUAUUG GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UCUUGUCU
4900





188
GAGCAAUA G UAAAACAC
1440
GUGUUUUA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UAUUGCUC
4901





202
CACAUCAG G UCAGGGGG
1441
CCCCCUGA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CUGAUGUG
4902





210
GUCAGGGG G UUAAAGAC
1442
GUCUUUAA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CCCCUGAC
4903





242
UCCGAUAA G UUGGAAAC
1443
GUUUCCAA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UUAUCGGA
4904





251
UUGGAAAC G UGUGUCUA
1444
UAGACACA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG GUUUCCAA
4905





287
AUAUAAUG G UAAAGAAA
1445
UUUCUUUA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CAUUAUAU
4906





305
ACACCUUC G UAACCCGC
1446
GCGGGUUA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG GAAGGUGU
4907





349
GAUGUACA G CAAUGGGG
1447
CCCCAUUG GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UGUACAUC
4908





357
GCAAUGGG G CCAUUUAA
1448
UUAAAUGG GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CCCAUUGC
4909





368
AUUUAAGA G UUCUGUGU
1449
ACACAGAA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UCUUAAAU
4910





406
UAGAAGGG G CCCUGAGU
1450
ACUCAGGG GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CCCUUCUA
4911





413
GGCCCUGA G UAAUUCAC
1451
GUGAAUUA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UCAGGGCC
4912





429
CUCAUUCA G CUGAACAA
1452
UUGUUCAG GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UGAAUGAG
4913





443
CAACAAUG G CUAUGAAG
1453
CUUCAUAG GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CAUUGUUG
4914





452
CUAUGAAG G CAUUGUCG
1454
CGACAAUG GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CUUCAUAG
4915





460
GCAUUGUC G UUGCAAUC
1455
GAUUGCAA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG GACAAUGC
4916





520
AGGACAUG G UGACCCAG
1456
CUGGGUCA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CAUGUCCU
4917





529
UGACCCAG G CAUCUCUG
1457
CAGAGAUG GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CUGGGUCA
4918





550
UGUUUGAA G CUACAGGA
1458
UCCUGUAG GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UUCAAACA
4919





561
ACAGGAAA G CGAUUUUA
1459
UAAAAUCG GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UUUCCUGU
4920





616
AGACAAAG G CUGACUAU
1460
AUAGUCAG GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CUUUGUCU
4921





667
AUGUUCUG G UUGCUGAG
1461
CUCAGCAA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CAGAACAU
4922





675
GUUGCUGA G UCUACUCC
1462
GGACUAGA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGCC UCCGGG UCAGCAAC
4923





689
UCCUCCAG G UAAUGAUG
1463
CAUCAUUA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CUGGAGGA
4924





711
UACACUGA G CAGAUGGG
1464
CCCAUCUG GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UCAGUGUA
4925





719
GCAGAUGG G CAACUGUG
1465
CACAGUUG GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CCAUCUGC
4926





737
AGAGAAGG G UGAAAGGA
1466
UCCUUUCA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CCUUCUCU
4927





780
GGAAAAAA G UUAGCUGA
1467
UCAGCUAA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UUUUUUCC
4928





784
AAAAGUUA G CUGAAUAU
1468
AUAUUCAG GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UAACUUUU
4929





803
ACCACAAG G UAAGGCAU
1469
AUGCCUUA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CUUGUGGU
4930





808
AAGGUAAG G CAUUUGUC
1470
GACAAAUG GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CUUACCUU
4931





822
GUCCAUGA G UGGGCUCA
1471
UGAGCCCA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UCAUGGAC
4932





826
AUGAGUGG G CUCAUCUA
1472
UAGAUGAG GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CCACUCAU
4933





844
GAUGGGGA G UAUUUGAC
1473
GUCAAAUA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UCCCCAUC
4934





855
UUUGACGA G UACAAUAA
1474
UUAUUGUA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UCGUCAAA
4935





901
GAAUACAA G CAGUAAGA
1475
UCUUACUG GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UUGUAUUC
4936





904
UACAAGCA G UAAGAUGU
1476
ACAUCUUA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UGCUUGUA
4937





916
GAUGUUCA G CAGGUAUU
1477
AAUACCUG GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UGAACAUC
4938





920
UUCAGCAG G UAUUACUG
1478
CAGUAAUA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CUGCUGAA
4939





929
UAUUACUG G UACAAAUG
1479
CAUUUGUA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CAGUAAUA
4940





940
CAAAUGUA G UAAAGAAG
1480
CUUCUUUA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UACAUUUG
4941





948
GUAAAGAA G UGUCAGGG
1481
CCCUGACA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UUCUUUAC
4942





959
UCAGGCAC G CAGCUGUU
1482
AACAGCUG GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CUCCCUGA
4943





962
GGGAGCCA G CUGUUACA
1483
UGUAACAG GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UGCCUCCC
4944





994
UCAAUAAA G UUACAGGA
1484
UCCUGUAA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UUUAUUGA
4945





1023
GGAUGUGA G UUUGUUCU
1485
AGAACAAA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UCACAUCC
4946





1054
CGGAGAAG G CUUCUAUA
1486
UAUAGAAG GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CUUCUCCG
4947





1090
AUUCUAUA G UUGAAUUC
1487
GAAUUCAA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UAUAGAAU
4948





1126
ACAAAGAA G CUCCAAAC
1488
GUUUGGAG GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UUCUUUGU
4949





1137
CCAAACAA G CAAAAUCA
1489
UGAUUUUG GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UUGUUUGG
4950





1163
UCUCCGAA G CACAUGGG
1490
CCCAUGUG GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UUCGGAGA
4951





1174
CAUGGGAA G UGAUCCGU
1491
ACGGAUCA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UUCCCAUG
4952





1181
AGUGAUCC G UGAUUCUG
1492
CAGAAUCA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG GGAUCACU
4953





1224
ACAACACA G CCACCAAA
1493
UUUGGUGG GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UGUGUUGU
4954





1279
UGUGUUUA G UCCUUGAC
1494
GUCAAGGA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UAAACACA
4955





1298
AUCUGGAA G CAUGGCGA
1495
UCGCCAUG GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UUCCAGAU
4956





1303
GAAGCAUG G CGACUGGU
1496
ACCAGUCG GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CAUGCUUC
4957





1310
GGCGACUG G UAACCGCC
1497
GGCGGUUA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CAGUCGCC
4958





1336
UGAAUCAA G CAGGCCAG
1498
CUGGCCUG GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UUGAUUCA
4959





1340
UCAAGCAG G CCAGCUUU
1499
AAAGCUGG GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CUGCUUGA
4960





1344
GCAGGCCA G CUUUUCCU
1500
AGGAAAAG GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UGGCCUGC
4961





1363
UGCAGACA G UUGAGCUG
1501
CAGCUCAA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UGUCUGCA
4962





1368
ACAGUUGA G CUGGGGUC
1502
GACCCCAG GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UCAACUGU
4963





1374
GAGCUGGG G UCCUGGGU
1503
ACCCAGGA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CCCAGCUC
4964





1381
GGUCCUGG G UUGGGAUG
1504
CAUCCCAA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CCAGGACC
4965





1390
UUGGGAUG G UGACAUUU
1505
AAAUGUCA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CAUCCCAA
4966





1403
AUUUGACA G UGCUGCCC
1506
GGGCAGCA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UGUCAAAU
4967





1421
UGUACAAA G UGAACUCA
1507
UGAGUUCA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UUUGUACA
4968





1442
GAUAAACA G UGGCAGUG
1508
CACUGCCA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UGUUUAUC
4969





1445
AAACAGUG G CAGUGACA
1509
UGUCACUG GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CACUGUUU
4970





1448
CAGUGGCA G UGACAGGG
1510
CCCUGUCA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UGCCACUG
4971





1483
UACCUGCA G CAGCUUCA
1511
UGAAGCUG GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UGCAGGUA
4972





1486
CUGCAGCA G CUUCAGGA
1512
UCCUGAAG GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UGCUGCAG
4973





1500
GGAGGGAC G UCCAUCUG
1513
CAGAUGGA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG GUCCCUCC
4974





1511
CAUCUGCA G CGGGCUUC
1514
GAAGCCCG GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UGCAGAUG
4975





1515
UGCAGCGG G CUUCGAUC
1515
GAUCGAAG GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CCGCUGCA
4976





1525
UUCGAUCG G CAUUUACU
1516
AGUAAAUG GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CGAUCGAA
4977





1607
CACUAUAA G UGGGUGCU
1517
AGCACCCA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UUAUAGUG
4978





1611
AUAAGUGG G UGCUUUAA
1518
UUAAAGCA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CCACUUAU
4979





1624
UUAACGAG G UCAAACAA
1519
UUGUUUGA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CUCGUUAA
4980





1634
CAAACAAA G UGGUGCCA
1520
UGGCACCA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UUUGUUUG
4981





1637
ACAAAGUG G UGCCAUCA
1521
UGAUGGCA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CACUUUGU
4982





1654
UCCACACA G UCGCUUUG
1522
CAAAGCGA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UGUGUGGA
4983





1665
GCUUUGGG G CCCUCUGC
1523
GCAGAGGG GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CCCAAAGC
4984





1675
CCUCUGCA G CUCAAGAA
1524
UUCUUGAG GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UGCAGAGG
4985





1692
CUAGAGGA G CUGUCCAA
1525
UUGGACAG GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UCCUCUAG
4986





1712
GACAGGAG G UUUACAGA
1526
UCUGUAAA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CUCCUGUC
4987





1738
CAGAUCAA G UUCAGAAC
1527
GUUCUGAA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UUGAUCUG
4988





1751
GAACAAUG G CCUCAUUG
1528
CAAUGAGG GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CAUUGUUC
4989





1771
CUUUUGGG G CCCUUUCA
1529
UGAAAGGG GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CCCAAAAG
4990





1792
GAAAUGGA G CUGUCUCU
1530
AGAGACAG GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UCCAUUUC
4991





1803
GUCUCUCA G CGCUCCAU
1531
AUGGAGCG GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UGAGAGAC
4992





1815
UCCAUCCA G CUUGAGAG
1532
CUCUCAAG GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UGGAUGGA
4993





1823
GCUUGAGA G UAAGGGAU
1533
AUCCCUUA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UCUCAAGC
4994





1847
CCAGAACA G CCAGUGGA
1534
UCCACUGG GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UGUUCUGG
4995





1851
AACAGCCA G UGGAUGAA
1535
UUCAUCCA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UGGCUGUU
4996





1862
GAUGAAUG G CACAGUGA
1536
UCACUGUG GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CAUUCAUC
4997





1867
AUGGCACA G UGAUCGUG
1537
CACGAUCA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UGUGCCAU
4998





1873
CAGUGAUC G UGGACAGC
1538
GCUGUCCA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG GAUCACUG
4999





1880
CGUGGACA G CACCGUGG
1539
CCACGGUG GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UGUCCACG
5000





1885
ACAGCACC G UGGGAAAG
1540
CUUUCCCA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG GGUGCUGU
5001





1926
ACAACGCA G CCUCCCCA
1541
UGGGGAGG GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UGCGUUGU
5002





1955
GGAUCCCA G UGGACAGA
1542
UCUGUCCA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UGGGAUCC
5003





1965
GGACAGAA G CAAGGUGG
1543
CCACCUUG GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UUCUGUCC
5004





1970
GAAGCAAG G UGGCUUUG
1544
CAAAGCCA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CUUGCUUC
5005





1973
GCAAGGUG G CUUUGUAG
1545
CUACAAAG GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CACCUUGC
5006





1981
GCUUUGUA G UGGACAAA
1546
UUUGUCCA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UACAAAGC
5007





2002
CCAAAAUG G CCUACCUC
1547
GAGGUAGG GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CAUUUUGG
5008





2021
AAUCCCAG G CAUUGCUA
1548
UAGCAAUG GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CUGGGAUU
5009





2032
UUGCUAAG G UUGGCACU
1549
AGUGCCAA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CUUAGCAA
5010





2036
UAAGGUUG G CACUUGGA
1550
UCCAAGUG GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CAACCUUA
5011





2051
GAAAUACA G UCUGCAAG
1551
CUUGCAGA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UGUAUUUC
5012





2059
GUCUGCAA G CAAGCUCA
1552
UGAGCUUG GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UUGCAGAC
5013





2063
GCAAGCAA G CUCACAAA
1553
UUUGUGAG GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UUGCUUGC
5014





2091
ACUGUCAC G UCCCGUGC
1554
GCACGGGA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG GUGACAGU
5015





2096
CACGUCCC G UGCGUCCA
1555
UGGACGCA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG GGGACGUG
5016





2100
UCCCGUGC G UCCAAUGC
1556
GCAUUGGA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG GCACGGGA
5017





2128
CAAUUACA G UGACUUCC
1557
GGAAGUCA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UGUAAUUG
5018





2156
GGACACCA G CAAAUUCC
1558
GGAAUUUG GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UGGUGUCC
5019





2168
AUUCCCCA G CCCUCUGG
1559
CCAGAGGG GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UGGGGAAU
5020





2176
GCCCUCUG G UAGUUUAU
1560
AUAAACUA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CAGAGGGC
5021





2179
CUCUGGUA G UUUAUGCA
1561
UGCAUAAA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UACCAGAG
5022





2203
GCCAAGGA G CCUCCCCA
1562
UGGGGAGG GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UCCUUGGC
5023





2221
UUCUCAGG G CCAGUGUC
1563
GACACUGG GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CCUGAGAA
5024





2225
CAGGGCCA G UGUCACAG
1564
CUGUGACA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UGGCCCUG
5025





2233
GUGUCACA G CCCUGAUU
1565
AAUCAGGG GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UGUGACAC
5026





2248
UUGAAUCA G UGAAUGGA
1566
UCCAUUCA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UGAUUCAA
5027





2263
GAAAAACA G UUACCUUG
1567
CAAGGUAA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UGUUUUUC
5028





2290
AUAAUGGA G CAGGUGCU
1568
AGCACCUG GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UCCAUUAU
5029





2294
UGGAGCAG G UGCUGAUG
1569
CAUCAGCA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CUGCUCCA
5030





2318
GGAUGACG G UGUCUACU
1570
AGUAGACA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CGUCAUCC
5031





2331
UACUCAAG G UAUUUCAC
1571
GUGAAAUA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CUUGAGUA
5032





2357
CACGAAUG G UAGAUACA
1572
UGUAUCUA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CAUUCGUG
5033





2366
UAGAUACA G UGUAAAAG
1573
CUUUUACA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UGUAUCUA
5034





2374
GUGUAAAA G UGCGGGCU
1574
AGCCCGCA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UUUUACAC
5035





2380
AAGUGCGG G CUCUGGGA
1575
UCCCAGAG GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CCGCACUU
5036





2392
UGGGAGGA G UUAACGCA
1576
UGCGUUAA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UCCUCCCA
5037





2401
UUAACGCA G CCAGACGG
1577
CCGUCUGG GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UGCGUUAA
5038





2413
GACGGAGA G UGAUACCC
1578
GGGUAUCA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UCUCCGUC
5039





2424
AUACCCCA G CAGAGUGG
1579
CCACUCUG GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UGGGGUAU
5040





2429
CCAGCAGA G UGGAGCAC
1580
GUGCUCCA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UCUGCUGG
5041





2434
AGAGUGGA G CACUGUAC
1581
GUACAGUG GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UCCACUCU
5042





2450
CAUACCUG G CUGGAUUG
1582
CAAUCCAG GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CAGGUAUG
5043





2523
CAACACAA G CAAGUGUG
1583
CACACUUG GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UUGUGUUG
5044





2527
ACAAGCAA G UGUGUUUC
1584
GAAACACA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UUGCUUGU
5045





2537
GUGUUUCA G CAGAACAU
1585
AUGUUCUG GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UGAAACAC
5046





2555
CUCGGGAG G CUCAUUUG
1586
CAAAUGAG GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CUCCCGAG
5047





2566
CAUUUGUG G CUUCUGAU
1587
AUCAGAAG GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CACAAAUG
5048





2612
CCCACCUG G CCAAAUCA
1588
UGAUUUGG GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CAGGUGGG
5049





2632
ACCUGAAG G CGGAAAUU
1589
AAUUUCCG GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CUUCAGGU
5050





2648
UCACGGGG G CAGUCUCA
1590
UGAGACUG GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CCCCGUGA
5051





2651
CGGGGGCA G UCUCAUUA
1591
UAAUGAGA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UGCCCCCG
5052





2674
CUUGGACA G CUCCUGGG
1592
CCCAGGAG GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UGUCCAAG
5053





2704
AUGGAACA G CUCACAAG
1593
CUUGUGAG GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UGUUCCAU
5054





2712
GCUCACAA G UAUAUCAU
1594
AUGAUAUA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UUGUGAGC
5055





2729
UCGAAUAA G UACAAGUA
1595
UACUUGUA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UUAUUCGA
5056





2735
AAGUACAA G UAUUCUUG
1596
CAAGAAUA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UUGUACUU
5057





2757
AGAGACAA G UUCAAUGA
1597
UCAUUGAA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UUGUCUCU
5058





2776
CUCUUCAA G UGAAUACU
1598
AGUAUUCA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UUGAAGAG
5059





2806
CAAAGGAA G CCAACUCU
1599
AGAGUUGG GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UUCCUUUG
5060





2821
CUGAGGAA G UCUUUUUG
1600
CAAAAAGA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UUCCUCAG
5061





2861
UGAAAAUG G CACAGAUC
1601
GAUCUGUG GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CAUUUUCA
5062





2887
CUAUUCAG G CUGUUGAU
1602
AUCAACAG GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CUGAAUAG
5063





2899
UUGAUAAG G UCGAUCUG
1603
CAGAUCGA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CUUAUCAA
5064





2935
UUGCACGA G UAUCUUUG
1604
CAAAGAUA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UCGUGCAA
5065





2978
GACACCUA G UCCUGAUG
1605
CAUCAGGA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UAGGUGUC
5066





2991
GAUGAAAC G UCUGCUCC
1606
GGAGCAGA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG GUUUCAUC
5067





3023
UAUCAACA G CACCAUUC
1607
GAAUGGUG GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UGUUGAUA
5068





3035
CAUUCCUG G CAUUCACA
1608
UGUGAAUG GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CAGGAAUG
5069





3063
AUGUGGAA G UGGAUAGG
1609
CCUAUCCA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UUCCACAU
5070





3081
GAACUGCA G CUGUCAAU
1610
AUUGACAG GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UGCAGUUC
5071





3091
UGUCAAUA G CCUAGGGC
1611
GCCCUAGG GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UAUUGACA
5072





3098
AGCCUAGG G CUGAAUUU
1612
AAAUUCAG GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CCUAGGCU
5073





3189
UGUAGGGG G CGAUAUAC
1613
GUAUAUCG GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CCCCUACA
5074





3242
UGUAGGGG G CGAUAUAC
1613
GUAUAUCG GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CCCCUACA
5074





3210
UGUAUAUA G UACAUUUA
1614
UAAAUGUA GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UAUAUACA
5075





3279
UGUAGGGG G CGAUAAAA
1615
UUUUAUCG GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CCCCUACA
5076





14
AUGCUUUU G GUACAAAU
1868
AUUUGUAC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AAAAGCAU
5077





23
GUACAAAU G GAUGUGGA
1869
UCCACAUC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AUUUGUAC
5078





24
UACAAAUG G AUGUGGAA
1870
UUCCACAU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CAUUUGUA
5079





29
AUGGAUGU G GAAUAUAA
1871
UUAUAUUC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG ACAUCCAU
5080





30
UGGAUGUG G AAUAUAAU
1872
AUUAUAUU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CACAUCCA
5081





58
UUGUUUAA G GGGAGCAU
1873
AUGCUCCC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UUAAACAA
5082





59
UGUUUAAG G GGAGCAUG
1874
CAUGCUCC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CUUAAACA
5083





60
GUUUAAGG G GAGCAUGA
1875
UCAUGCUC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CCUUAAAC
5084





61
UUUAAGGG G AGCAUGAA
1876
UUCAUGCU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CCCUUAAA
5085





70
AGCAUGAA G AGGUGUUG
1877
CAACACCU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UUCAUGCU
5086





72
CAUGAAGA G GUGUUGAG
1878
CUCAACAC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UCUUCAUG
5087





80
GGUGUUGA G GUUAUGUC
1879
GACAUAAC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UCAACACC
5088





97
AAGCAUCU G GCACAGCU
1880
AGCUGUGC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AGAUGCUU
5089





109
CAGCUGAA G GCAGAUGG
1881
CCAUCUGC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UUCAGCUG
5090





113
UGAAGGCA G AUGGAAAU
1882
AUUUCCAU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UGCCUUCA
5091





116
AGGCAGAU G GAAAUAUU
1883
AAUAUUUC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AUCUGCCU
5092





117
GGCAGAUG G AAAUAUUU
1884
AAAUAUUU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CAUCUGCC
5093





143
CAAUUUGA G ACUAAGAU
1885
AUCUUAGU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UCAAAUUG
5094





149
GAGACUAA G AUAUUGUU
1886
AACAAUAU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UUAGUCUC
5095





175
CUAUUGAA G ACAAGAGC
1887
GCUCUUGU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UUCAAUAG
5096





180
GAAGACAA G AGCAAUAG
1888
CUAUUGCU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UUGUCUUC
5097





201
ACACAUCA G GUCAGGGG
1889
CCCCUGAC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UGAUGUGU
5098





206
UCAGGUCA G GGGGUUAA
1890
UUAACCCC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UGACCUGA
5099





207
CAGGUCAG G GGGUUAAA
1891
UUUAACCC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CUGACCUG
5100





208
AGGUCAGG G GGUUAAAG
1892
CUUUAACC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CCUGACCU
5101





209
GGUCAGGG G GUUAAAGA
1893
UCUUUAAC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CCCUGACC
5102





216
GGGUUAAA G ACCUGUGA
1894
UCACAGGU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UUUAACCC
5103





245
GAUAAGUU G GAAACGUG
1895
CACGUUUC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AACUUAUC
5104





246
AUAAGUUG G AAACGUGU
1896
ACACGUUU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CAACUUAU
5105





286
UAUAUAAU G GUAAAGAA
1897
UUCUUUAC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AUUAUAUA
5106





292
AUGGUAAA G AAAGACAC
1898
GUGUCUUU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UUUACCAU
5107





296
UAAAGAAA G ACACCUUC
1899
GAAGGUGU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UUUCUUUA
5108





324
UUUCCAAA G AGAGGAAU
1900
AUUCCUCU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UUUGGAAA
5109





326
UCCAAAGA G AGGAAUCA
1901
UGAUUCCU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UCUUUGGA
5110





328
CAAAGAGA G GAAUCACA
1902
UGUGAUUC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UCUCUUUG
5111





329
AAAGAGAG G AAUCACAG
1903
CUGUGAUU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CUCUCUUU
5112





337
GAAUCACA G GGAGAUGU
1904
ACAUCUCC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UGUGAUUC
5113





338
AAUCACAG G GAGAUGUA
1905
UACAUCUC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CUGUGAUU
5114





339
AUCACAGG G AGAUGUAC
1906
GUACAUCU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CCUGUGAU
5115





341
CACAGGGA G AUGUACAG
1907
CUGUACAU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UCCCUGUG
5116





354
ACAGCAAU G GGGCCAUU
1908
AAUGGCCC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AUUGCUGU
5117





355
CAGCAAUG G GGCCAUUU
1909
AAAUGGCC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CAUUGCUG
5118





356
AGCAAUGG G GCCAUUUA
1910
UAAAUGGC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CCAUUGCU
5119





366
CCAUUUAA G AGUUCUGU
1911
ACAGAACU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UUAAAUGG
5120





400
ACCUUCUA G AAGGGGCC
1912
GGCCCCUU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UAGAAGGU
5121





403
UUCUAGAA G GGGCCCUG
1913
CAGGGCCC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UUCUAGAA
5122





404
UCUAGAAG G GGCCCUGA
1914
UCAGGGCC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CUUCUAGA
5123





405
CUAGAAGG G GCCCUGAG
1915
CUCAGGGC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CCUUCUAG
5124





442
ACAACAAU G GCUAUGAA
1916
UUCAUAGC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AUUGUUGU
5125





451
GCUAUGAA G GCAUUGUC
1917
GACAAUGC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UUCAUAGC
5126





484
AUGUGCCA G AAGAUGAA
1918
UUCAUCUU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UGGCACAU
5127





487
UGCCAGAA G AUGAAACA
1919
UGUUUCAU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UUCUGGCA
5128





513
CAAAUAAA G GACAUGGU
1920
ACCAUGUC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UUUAUUUG
5129





514
AAAUAAAG G ACAUGGUG
1921
CACCAUGU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CUUUAUUU
5130





519
AAGGACAU G GUGACCCA
1922
UGGGUCAC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AUGUCCUU
5131





528
GUGACCCA G GCAUCUCU
1923
AGAGAUGC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UGGGUCAC
5132





556
AAGCUACA G GAAAGCGA
1924
UCGCUUUC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UGUAGCUU
5133





557
AGCUACAG G AAAGCGAU
1925
AUCGCUUU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CUGUAGCU
5134





605
UGAAACAU G GAAGACAA
1926
UUGUCUUC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AUGUUUCA
5135





606
GAAACAUG G AAGACAAA
1927
UUUGUCUU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CAUGUUUC
5136





609
ACAUGGAA G ACAAAGGC
1928
GCCUUUGU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UUCCAUGU
5137





615
AAGACAAA G GCUGACUA
1929
UAGUCAGC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UUUGUCUU
5138





629
CUAUGUGA G ACCAAAAC
1930
GUUUUGGU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UCACAUAG
5139





642
AAACUUGA G ACCUACAA
1931
UUGUAGGU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UCAAGUUU
5140





666
GAUGUUCU G GUUGCUGA
1932
UCAGCAAC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AGAACAUC
5141





688
CUCCUCCA G GUAAUGAU
1933
AUCAUUAC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UGGAGGAG
5142





714
ACUGAGCA G AUGGGCAA
1934
UUGCCCAU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UGCUCAGU
5143





717
GAGCAGAU G GGCAACUG
1935
CAGUUGCC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AUCUGCUC
5144





718
AGCAGAUG G GCAACUGU
1936
ACAGUUGC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CAUCUGCU
5145





727
GCAACUGU G GAGAGAAG
1937
CUUCUCUC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG ACAGUUGC
5146





728
CAACUGUG G AGAGAAGG
1938
CCUUCUCU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CACAGUUG
5147





730
ACUGUGGA G AGAAGGGU
1939
ACCCUUCU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UCCACAGU
5148





732
UGUGGAGA G AAGGGUGA
1940
UCACCCUU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UCUCCACA
5149





735
GGAGAGAA G GGUGAAAG
1941
CUUUCACC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UUCUCUCC
5150





736
GAGAGAAG G GUGAAAGG
1942
CCUUUCAC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CUUCUCUC
5151





743
GGGUGAAA G GAUCCACC
1943
GGUGGAUC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UUUCACCC
5152





744
GGUGAAAG G AUCCACCU
1944
AGGUGGAU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CUUUCACC
5153





772
UCAUUGCA G GAAAAAAG
1945
CUUUUUUC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UGCAAUGA
5154





773
CAUUGCAG G AAAAAAGU
1946
ACUUUUUU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CUGCAAUG
5155





793
CUGAAUAU G GACCACAA
1947
UUGUGGUC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AUAUUCAG
5156





794
UGAAUAUG G ACCACAAG
1948
CUUGUGGU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CAUAUUCA
5157





802
GACCACAA G GUAAGGCA
1949
UGCCUUAC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UUGUGGUC
5158





807
CAAGGUAA G GCAUUUGU
1950
ACAAAUGC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UUACCUUG
5159





824
CCAUGAGU G GGCUCAUC
1951
GAUGAGCC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG ACUCAUGG
5160





825
CAUGAGUG G GCUCAUCU
1952
AGAUGAGC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CACUCAUG
5161





839
UCUACGAU G GGGAGUAU
1953
AUACUCCC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AUCGUAGA
5162





840
CUACGAUG G GGAGUAUU
1954
AAUACUCC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CAUCGUAG
5163





841
UACGAUGG G GAGUAUUU
1955
AAAUACUC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CCAUCGUA
5164





842
ACGAUGGG G AGUAUUUG
1956
CAAAUACU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CCCAUCGU
5165





870
AAUGAUGA G AAAUUCUA
1957
UAGAAUUU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UCAUCAUU
5166





889
UAUCCAAU G GAAGAAUA
1958
UAUUCUUC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AUUGGAUA
5167





890
AUCCAAUG G AAGAAUAC
1959
GUAUUCUU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CAUUGGAU
5168





893
CAAUGGAA G AAUACAAG
1960
CUUGUAUU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UUCCAUUG
5169





908
AGCAGUAA G AUGUUCAG
1961
CUGAACAU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UUACUGCU
5170





919
GUUCAGCA G GUAUUACU
1962
AGUAAUAC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UGCUGAAC
5171





928
GUAUUACU G GUACAAAU
1963
AUUUGUAC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AGUAAUAC
5172





945
GUAGUAAA G AAGUGUCA
1964
UGACACUU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UUUACUAC
5173





954
AAGUGUCA G GGAGGCAG
1965
CUGCCUCC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UGACACUU
5174





955
AGUGUCAG G GAGGCAGC
1966
GCUGCCUC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CUGACACU
5175





956
GUGUCAGG G AGGCAGCU
1967
AGCUGCCU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CCUGACAC
5176





958
GUCAGGGA G GCAGCUGU
1968
ACAGCUGC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UCCCUGAC
5177





977
CACCAAAA G AUGCACAU
1969
AUGUGCAU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UUUUGGUG
5178





1000
AAGUUACA G GACUCUAU
1970
AUAGAGUC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UGUAACUU
5179





1001
AGUUACAG G ACUCUAUG
1971
CAUAGAGU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CUGUAACU
5180





1015
AUGAAAAA G GAUGUGAG
1972
CUCACAUC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UUUUUCAU
5181





1016
UGAAAAAG G AUGUGAGU
1973
ACUCACAU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CUUUUUCA
5182





1044
UCCCGCCA G ACGGAGAA
1974
UUCUCCGU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UGGCGGGA
5183





1047
CGCCAGAC G GAGAAGGC
1975
GCCUUCUC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG GUCUGGCG
5184





1048
GCCAGACG G AGAAGGCU
1976
AGCCUUCU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CGUCUGGC
5185





1050
CAGACGGA G AAGGCUUC
1977
GAAGCCUU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UCCGUCUG
5186





1053
ACGGAGAA G GCUUCUAU
1978
AUAGAAGC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UUCUCCGU
5187





1105
UCUGUACA G AACAAAAC
1979
GUUUUGUU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UGUACAGA
5188





1123
ACAACAAA G AAGCUCCA
1980
UGGAGCUU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UUUGUUGU
5189





1169
AAGCACAU G GGAAGUGA
1981
UCACUUCC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AUGUGCUU
5190





1170
AGCACAUG G GAAGUGAU
1982
AUCACUUC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CAUGUGCU
5191





1171
GCACAUGG G AAGUGAUC
1983
GAUCACUU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CCAUGUGC
5192





1191
GAUUCUGA G GACUUUAA
1984
UUAAAGUC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UCAGAAUC
5193





1192
AUUCUGAG G ACUUUAAG
1985
CUUAAAGU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CUCAGAAU
5194





1200
GACUUUAA G AAAACCAC
1986
GUGGUUUU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UUAAAGUC
5195





1254
UUGCUGCA G AUUGGACA
1987
UGUCCAAU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UGCAGCAA
5196





1258
UGCAGAUU G GACAAAGA
1988
UCUUUGUC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AAUCUGCA
5197





1259
GCAGAUUG G ACAAAGAA
1989
UUCUUUGU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CAAUCUGC
5198





1265
UGGACAAA G AAUUGUGU
1990
ACACAAUU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UUUGUCCA
5199





1294
ACAAAUCU G GAAGCAUG
1991
CAUGCUUC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AGAUUUGU
5200





1295
CAAAUCUG G AAGCAUGG
1992
CCAUGCUU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CAGAUUUG
5201





1302
GGAAGCAU G GCGACUGG
1993
CCAGUCGC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AUGCUUCC
5202





1309
UGGCGACU G GUAACCGC
1994
GCGGUUAC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AGUCGCCA
5203





1339
AUCAAGCA G GCCAGCUU
1995
AAGCUGGC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UGCUUGAU
5204





1359
CUGCUGCA G ACAGUUGA
1996
UCAACUGU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UGCAGCAG
5205





1371
GUUGAGCU G GGGUCCUG
1997
CAGGACCC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AGCUCAAC
5206





1372
UUGAGCUG G GGUCCUGG
1998
CCAGGACC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CAGCUCAA
5207





1373
UGAGCUGG G GUCCUGGG
1999
CCCAGGAC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CCAGCUCA
5208





1379
GGGGUCCU G GGUUGGGA
2000
UCCCAACC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AGGACCCC
5209





1380
GGGUCCUG G GUUGGGAU
2001
AUCCCAAC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CAGGACCC
5210





1384
CCUGGGUU G GGAUGGUG
2002
CACCAUCC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AACCCAGG
5211





1385
CUGGGUUG G GAUGGUGA
2003
UCACCAUC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CAACCCAG
5212





1386
UGGGUUGG G AUGGUGAC
2004
GUCACCAU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CCAACCCA
5213





1389
GUUGGGAU G GUGACAUU
2005
AAUGUCAC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AUCCCAAC
5214





1434
CUCAUACA G AUAAACAG
2006
CUGUUUAU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UGUAUGAG
5215





1444
UAAACAGU G GCAGUGAC
2007
GUCACUGC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG ACUGUUUA
5216





1454
CAGUGACA G GGACACAC
2008
GUGUGUCC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UGUCACUG
5217





1455
AGUGACAG G GACACACU
2009
AGUGUGUC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CUGUCACU
5218





1456
GUGACAGG G ACACACUC
2010
GAGUGUGU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CCUGUCAC
5219





1472
CGCCAAAA G AUUACCUG
2011
CAGGUAAU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UUUUGGCG
5220





1492
CAGCUUCA G GAGGGACG
2012
CGUCCCUC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UGAAGCUG
5221





1493
AGCUUCAG G AGGGACGU
2013
ACGUCCCU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CUGAAGCU
5222





1495
CUUCAGGA G GGACGUCC
2014
GGACGUCC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UCCUGAAG
5223





1496
UUCAGGAG G GACGUCCA
2015
UGGACGUC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CUCCUGAA
5224





1497
UCAGGAGG G ACGUCCAU
2016
AUGGACGU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CCUCCUGA
5225





1513
UCUGCAGC G GGCUUCGA
2017
UCGAAGCC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG GCUGCAGA
5226





1514
CUGCAGCG G GCUUCGAU
2018
AUCGAAGC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CGCUGCAG
5227





1524
CUUCGAUC G GCAUUUAC
2019
GUAAAUGC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG GAUCGAAG
5228





1541
UGUGAUUA G GAAGAAAU
2020
AUUUCUUC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UAAUCACA
5229





1542
GUGAUUAG G AAGAAAUA
2021
UAUUUCUU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CUAAUCAC
5230





1545
AUUAGGAA G AAAUAUCC
2022
GGAUAUUU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UUCCUAAU
5231





1561
CAACUGAU G GAUCUGAA
2023
UUCAGAUC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AUCAGUUG
5232





1562
AACUGAUG G AUCUGAAA
2024
UUUCAGAU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CAUCAGUU
5233





1584
CUGCUGAC G GAUGGGGA
2025
UCCCCAUC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG GUCAGCAG
5234





1585
UGCUGACG G AUGGGGAA
2026
UUCCCCAU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CGUCAGCA
5235





1588
UGACGGAU G GGGAAGAC
2027
GUCUUCCC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AUCCGUCA
5236





1589
GACGGAUG G GGAAGACA
2028
UGUCUUCC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CAUCCGUC
5237





1590
ACGGAUGG G GAAGACAA
2029
UUGUCUUC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CCAUCCGU
5238





1591
CGGAUGGG G AAGACAAC
2030
GUUGUCUU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CCCAUCCG
5239





1594
AUGGGGAA G ACAACACU
2031
AGUGUUGU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UUCCCCAU
5240





1609
CUAUAAGU G GGUGCUUU
2032
AAAGCACC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG ACUUAUAG
5241





1610
UAUAAGUG G GUGCUUUA
2033
UAAAGCAC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CACUUAUA
5242





1623
UUUAACGA G GUCAAACA
2034
UGUUUGAC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UCGUUAAA
5243





1636
AACAAAGU G GUGCCAUC
2035
GAUGGCAC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG ACUUUGUU
5244





1662
GUCGCUUU G GGGCCCUC
2036
GAGGGCCC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AAAGCGAC
5245





1663
UCGCUUUG G GGCCCUCU
2037
AGAGGGCC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CAAAGCGA
5246





1664
CGCUUUGG G GCCCUCUG
2038
CAGAGGGC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CCAAAGCG
5247





1681
CAGCUCAA G AACUAGAG
2039
CUCUAGUU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UUGAGCUG
5248





1687
AAGAACUA G AGGAGCUG
2040
CAGCUCCU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UAGUUCUU
5249





1689
GAACUAGA G GAGCUGUC
2041
GACAGCUC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UCUAGUUC
5250





1690
AACUAGAG G AGCUGUCC
2042
GGACAGCU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CUCUAGUU
5251





1708
AAAUGACA G GAGGUUUA
2043
UAAACCUC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UGUCAUUU
5252





1709
AAUGACAG G AGGUUUAC
2044
GUAAACCU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CUGUCAUU
5253





1711
UGACAGGA G GUUUACAG
2045
CUGUAAAC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UCCUGUCA
5254





1719
GGUUUACA G ACAUAUGC
2046
GCAUAUGU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UGUAAACC
5255





1732
AUGCUUCA G AUCAAGUU
2047
AACUUGAU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UGAAGCAU
5256





1743
CAAGUUCA G AACAAUGG
2048
CCAUUGUU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UGAACUUG
5257





1750
AGAACAAU G GCCUCAUU
2049
AAUGAGGC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AUUGUUCU
5258





1768
AUGCUUUU G GGGCCCUU
2050
AAGGGCCC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AAAAGCAU
5259





1769
UGCUUUUG G GGCCCUUU
2051
AAAGGGCC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CAAAAGCA
5260





1770
GCUUUUGG G GCCCUUUC
2052
GAAAGGGC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CCAAAAGC
5261





1783
UUUCAUCA G GAAAUGGA
2053
UCCAUUUC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UGAUGAAA
5262





1784
UUCAUCAG G AAAUGGAG
2054
CUCCAUUU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CUGAUGAA
5263





1789
CAGGAAAU G GAGCUGUC
2055
GACAGCUC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AUUUCCUG
5264





1790
AGGAAAUG G AGCUGUCU
2056
AGACAGCU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CAUUUCCU
5265





1821
CAGCUUGA G AGUAAGGG
2057
CCCUUACU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UCAAGCUG
5266





1827
GAGAGUAA G GGAUUAAC
2058
GUUAAUCC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UUACUCUC
5267





1828
AGAGUAAG G GAUUAACC
2059
GGUUAUUC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CUUACUCU
5268





1829
GAGUAAGG G AUUAACCC
2060
GGGUUAAU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CCUUACUC
5269





1842
ACCCUCCA G AACAGCCA
2061
UGGCUGUU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UGGAGGGU
5270





1853
CAGCCAGU G GAUGAAUG
2062
CAUUCAUC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG ACUGGCUG
5271





1854
AGCCAGUG G AUGAAUGG
2063
CCAUUCAU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CACUGGCU
5272





1861
GGAUGAAU G GCACAGUG
2064
CACUGUGC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AUUCAUCC
5273





1875
GUGAUCGU G GACAGCAC
2065
GUGCUGUC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG ACGAUCAC
5274





1876
UGAUCGUG G ACAGCACC
2066
GGUGCUGU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CACGAUCA
5275





1887
AGCACCGU G GGAAAGGA
2067
UCCUUUCC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG ACGGUGCU
5276





1888
GCACCGUG G GAAAGGAC
2068
GUCCUUUC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CACGGUGC
5277





1889
CACCGUGG G AAAGGACA
2069
UGUCCUUU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CCACGGUG
5278





1893
GUGGGAAA G GACACUUU
2070
AAAGUGUC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UUUCCCAC
5279





1894
UGGGAAAG G ACACUUUG
2071
CAAAGUGU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CUUUCCCA
5280





1916
UAUCACCU G GACAACGC
2072
GCGUUGUC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AGGUGAUA
5281





1917
AUCACCUG G ACAACGCA
2073
UGCGUUGU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CAGGUGAU
5282





1946
CCUUCUCU G GGAUCCCA
2074
UGGGAUCC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AGAGAAGG
5283





1947
CUUCUCUG G GAUCCCAG
2075
CUGGGAUC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CAGAGAAG
5284





1948
UUCUCUGG G AUCCCAGU
2076
ACUGGGAU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CCAGAGAA
5285





1957
AUCCCAGU G GACAGAAG
2077
CUUCUGUC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG ACUGGGAU
5286





1958
UCCCAGUG G ACAGAAGC
2078
GCUUCUGU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CACUGGGA
5287





1962
AGUGGACA G AAGCAAGG
2079
CCUUGCUU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UGUCCACU
5288





1969
AGAAGCAA G GUGGCUUU
2080
AAAGCCAC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UUGCUUCU
5289





1972
AGCAAGGU G GCUUUGUA
2081
UACAAAGC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG ACCUUGCU
5290





1983
UUUGUAGU G GACAAAAA
2082
UUUUUGUC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG ACUACAAA
5291





1984
UUGUAGUG G ACAAAAAC
2083
GUUUUUGU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CACUACAA
5292





2001
ACCAAAAU G GCCUACCU
2084
AGGUAGGC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AUUUUGGU
5293





2020
AAAUCCCA G GCAUUGCU
2085
AGCAAUGC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UGGGAUUU
5294





2031
AUUGCUAA G GUUGGCAC
2086
GUGCCAAC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UUAGCAAU
5295





2035
CUAAGGUU G GCACUUGG
2087
CCAAGUGC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AACCUUAG
5296





2042
UGGCACUU G GAAAUACA
2088
UGUAUUUC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AAGUGCCA
5297





2043
GGCACUUG G AAAUACAG
2089
CUGUAUUU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CAAGUGCC
5298





2148
ACGAACAA G GACACCAG
2090
CUGGUGUC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UUGUUCGU
5299





2149
CGAACAAG G ACACCAGC
2091
GCUGGUGU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CUUGUUCG
5300





2175
AGCCCUCU G GUAGUUUA
2092
UAAACUAC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AGAGGGCU
5301





2200
UUCGCCAA G GAGCCUCC
2093
GGAGGCUC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UUGGCGAA
5302





2201
UCGCCAAG G AGCCUCCC
2094
GGGAGGCU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CUUGGCGA
5303





2219
AAUUCUCA G GGCCAGUG
2095
CACUGGCC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UGAGAAUU
5304





2220
AUUCUCAG G GCCAGUGU
2096
ACACUGGC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CUGAGAAU
5305





2254
CAGUGAAU G GAAAAACA
2097
UGUUUUUC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AUUCACUG
5306





2255
AGUGAAUG G AAAAACAG
2098
CUGUUUUU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CAUUCACU
5307





2271
GUUACCUU G GAACUACU
2099
AGUAGUUC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AAGGUAAC
5308





2272
UUACCUUG G AACUACUG
2100
CAGUAGUU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CAAGGUAA
5309





2280
GAACUACU G GAUAAUGG
2101
CCAUUAUC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AGUAGUUC
5310





2281
AACUACUG G AUAAUGGA
2102
UCCAUUAU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CAGUAGUU
5311





2287
UGGAUAAU G GAGCAGGU
2103
ACCUGCUC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AUUAUCCA
5312





2288
GGAUAAUG G AGCAGGUG
2104
CACCUGCU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CAUUAUCC
5313





2293
AUGGAGCA G GUGCUGAU
2105
AUCAGCAC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UGCUCCAU
5314





2310
GCUACUAA G GAUGACGG
2106
CCGUCAUC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UUAGUAGC
5315





2311
CUACUAAG G AUGACGGU
2107
ACCGUCAU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CUUAGUAG
5316





2317
AGGAUGAC G GUGUCUAC
2108
GUAGACAC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG GUCAUCCU
5317





2330
CUACUCAA G GUAUUUCA
2109
UGAAAUAC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UUGAGUAG
5318





2356
ACACGAAU G GUAGAUAC
2110
GUAUCUAC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AUUCGUGU
5319





2360
GAAUGGUA G AUACAGUG
2111
CACUGUAU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UACCAUUC
5320





2378
AAAAGUGC G GGCUCUGG
2112
CCAGAGCC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG GCACUUUU
5321





2379
AAAGUGCG G GCUCUGGG
2113
CCCAGAGC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CGCACUUU
5322





2385
CGGGCUCU G GGAGGAGU
2114
ACUCCUCC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AGAGCCCG
5323





2386
GGGCUCUG G GAGGAGUU
2115
AACUCCUC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CAGAGCCC
5324





2387
GGCUCUGG G AGGAGUUA
2116
UAACUCCU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CCAGAGCC
5325





2389
CUCUGGGA G GAGUUAAC
2117
GUUAACUC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UCCCAGAG
5326





2390
UCUGGGAG G AGUUAACG
2118
CGUUAACU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CUCCCAGA
5327





2405
CGCAGCCA G ACGGAGAG
2119
CUCUCCGU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UGGCUGCG
5328





2408
AGCCAGAC G GAGAGUGA
2120
UCACUCUC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG GUCUGGCU
5329





2409
GCCAGACG G AGAGUGAU
2121
AUCACUCU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CGUCUGGC
5330





2411
CAGACGGA G AGUGAUAC
2122
GUAUCACU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UCCGUCUG
5331





2427
CCCCAGCA G AGUGGAGC
2123
GCUCCACU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UGCUGGGG
5332





2431
AGCAGAGU G GAGCACUG
2124
CAGUGCUC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG ACUCUGCU
5333





2432
GCAGAGUG G AGCACUGU
2125
ACAGUGCU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CACUCUGC
5334





2449
ACAUACCU G GCUGGAUU
2126
AAUCCAGC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AGGUAUGU
5335





2453
ACCUGGCU G GAUUGAGA
2127
UCUCAAUC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AGCCAGGU
5336





2454
CCUGGCUG G AUUGAGAA
2128
UUCUCAUU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CAGCCAGG
5337





2460
UGGAUUGA G AAUGAUGA
2129
UCAUCAUU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UCAAUCCA
5338





2477
AAUACAAU G GAAUCCAC
2130
GUGGAUUC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AUUGUAUU
5339





2478
AUACAAUG G AAUCCACC
2131
GGUGGAUU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CAUUGUAU
5340





2489
UCCACCAA G ACCUGAAA
2132
UUUCAGGU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UUGGUGGA
5341





2505
AUUAAUAA G GAUGAUGU
2133
ACAUCAUC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UUAUUAAU
5342





2506
UUAAUAAG G AUGAUGUU
2134
AACAUCAU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CUUAUUAA
5343





2540
UUUCAGCA G AACAUCCU
2135
AGGAUGUU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UGCUGAAA
5344





2550
ACAUCCUC G GGAGGCUC
2136
GAGCCUCC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG GAGGAUGU
5345





2551
CAUCCUCG G GAGGCUCA
2137
UGAGCCUC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CGAGGAUG
5346





2552
AUCCUCGG G AGGCUCAU
2138
AUGAGCCU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CCGAGGAU
5347





2554
CCUCGGGA G GCUCAUUU
2139
AAAUGAGC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UCCCGAGG
5348





2565
UCAUUUGU G GCUUCUGA
2140
UCAGAAGC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG ACAAAUGA
5349





2611
UCCCACCU G GCCAAAUC
2141
GAUUUGGC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AGGUGGGA
5350





2631
GACCUGAA G GCGGAAAU
2142
AUUUCCGC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UUCAGGUC
5351





2634
CUGAAGGC G GAAAUUCA
2143
UGAAUUUC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG GCCUUCAG
5352





2635
UGAAGGCG G AAAUUCAC
2144
GUGAAUUU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CGCCUUCA
5353





2644
AAAUUCAC G GGGGCAGU
2145
ACUGCCCC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG GUGAAUUU
5354





2645
AAUUCACG G GGGCAGUC
2146
GACUGCCC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CGUGAAUU
5355





2646
AUUCACGG G GGCAGUCU
2147
AGACUGCC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CCGUGAAU
5356





2647
UUCACGGG G GCAGUCUC
2148
GAGACUGC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CCCGUGAA
5357





2669
UCUGACUU G GACAGCUC
2149
GAGCUGUC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AAGUCAGA
5358





2670
CUGACUUG G ACAGCUCC
2150
GGAGCUGU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CAAGUCAG
5359





2680
CAGCUCCU G GGGAUGAU
2151
AUCAUCCC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AGGAGCUG
5360





2681
AGCUCCUG G GGAUGAUU
2152
AAUCAUCC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CAGGAGCU
5361





2682
GCUCCUGG G GAUGAUUA
2153
UAAUCAUC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CCAGGAGC
5362





2683
CUCCUGGG G AUGAUUAU
2154
AUAAUCAU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CCCAGGAG
5363





2698
AUGACCAU G GAACAGCU
2155
AGCUGUUC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AUGGUCAU
5364





2699
UGACCAUG G AACAGCUC
2156
GAGCUGUU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CAUGGUCA
5365





2750
UGAUCUCA G AGACAAGU
2157
ACUUGUCU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UGAGAUCA
5366





2752
AUCUCAGA G ACAAGUUC
2158
GAACUUGU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UCUGAGAU
5367





2802
AUCCCAAA G GAAGCCAA
2159
UUGGCUUC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UUUGGGAU
5368





2803
UCCCAAAG G AAGCCAAC
2160
GUUGGCUU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CUUUGGGA
5369





2817
AACUCUGA G GAAGUCUU
2161
AAGACUUC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UCAGAGUU
5370





2818
ACUCUGAG G AAGUCUUU
2162
AAAGACUU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CUCAGAGU
5371





2839
UUAAACCA G AAAACAUU
2163
AAUGUUUU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UGGUUUAA
5372





2860
UUGAAAAU G GCACAGAU
2164
AUCUGUGC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AUUUUCAA
5373





2866
AUGGCACA G AUCUUUUC
2165
GAAAAGAU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UGUGCCAU
5374





2886
GCUAUUCA G GCUGUUGA
2166
UCAACAGC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UGAAUAGC
5375





2898
GUUGAUAA G GUCGAUCU
2167
AGAUCGAC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UUAUCAAC
5376





2914
UGAAAUCA G AAAUAUCC
2168
GGAUAUUU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UGAUUUCA
5377





2958
CCUCCACA G ACUCCGCC
2169
GGCGGAGU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UGUGGAGG
5378





2968
CUCCGCCA G AGACACCU
2170
AGGUGUCU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UGGCGGAG
5379





2970
CCGCCAGA G ACACCUAG
2171
CUAGGUGU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UCUGGCGG
5380





3034
CCAUUCCU G GCAUUCAC
2172
GUGAAUGC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG AGGAAUGG
5381





3059
AAUUAUGU G GAAGUGGA
2173
UCCACUUC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG ACAUAAUU
5382





3060
AUUAUGUG G AAGUGGAU
2174
AUCCACUU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CACAUAAU
5383





3065
GUGGAAGU G GAUAGGAG
2175
CUCCUAUC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG ACUUCCAC
5384





3066
UGGAAGUG G AUAGGAGA
2176
UCUCCUAU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CACUUCCA
5385





3070
AGUGGAUA G GAGAACUG
2177
CAGUUCUC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UAUCCACU
5386





3071
GUGGAUAG G AGAACUGC
2178
GCAGUUCU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CUAUCCAC
5387





3073
GGAUAGGA G AACUGCAG
2179
CUGCAGUU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UCCUAUCC
5388





3096
AUAGCCUA G GGCUGAAU
2180
AUUCAGCC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UAGGCUAU
5389





3097
UAGCCUAG G GCUGAAUU
2181
AAUUCAGC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CUAGGCUA
5390





3113
UUUUGUCA G AUAAAUAA
2182
UUAUUUAU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UGACAAAA
5391





3174
GUAUUUUA G ACUUCCUG
2183
CAGGAAGU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UAAAAUAC
5392





3264
GUAUUUUA G ACUUCCUG
2183
CAGGAAGU GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UAAAAUAC
5392





3185
UUCCUGUA G GGGGCGAU
2184
AUCGCCCC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UACAGGAA
5393





3238
UUCCUGUA G GGGGCGAU
2184
AUCGCCCC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UACAGGAA
5393





3275
UUCCUGUA G GGGGCGAU
2184
AUCGCCCC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG UACAGGAA
5393





3186
UCCUGUAG G GGGCGAUA
2185
UAUCGCCC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CUACAGGA
5394





3239
UCCUGUAG G GGGCGAUA
2185
UAUCGCCC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CUACAGGA
5394





3276
UCCUGUAG G GGGCGAUA
2185
UAUCGCCC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CUACAGGA
5394





3187
CCUGUAGG G GGCGAUAU
2186
AUAUCGCC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CCUACAGG
5395





3240
CCUGUAGG G GGCGAUAU
2186
AUAUCGCC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CCUACAGG
5395





3188
CUGUAGGG G GCGAUAUA
2187
UAUAUCGC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CCCUACAG
5396





3241
CUGUAGGG G GCGAUAUA
2187
UAUAUCGC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CCCUACAG
5396





3277
CCUGUAGG G GGCGAUAA
2188
UUAUCGCC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CCUACAGG
5397





3278
CUGUAGGG G GCGAUAAA
2189
UUUAUCGC GGA GCCGUUAGGC UCCCUUCAAGGA GCCGUUAGGC UCCGGG CCCUACAG
5398






Input Sequence = NM_001285. Cut Site = G/.




Arm Length = 8. Core Sequence = GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG




Underlined region can be any X sequence or linker, as described herein.




NM_001285 (Homo sapiens chloride channel, calcium activated, 1 (CLCA1) mRNA, 3311 bp)








[0196]

9





TABLE IX










Human CLCA1 GeneBloc and Target Sequence 249.021
























Substrate



Rz


Pos
Substrate
Seq ID No.
RPI#
Alias
GeneBloc
Seq ID No.
















821
CAAGGUAAGGCAUUUGUCCAUGA
5399
19843
hCLCA1:821L23 GB3.3


B
ucauggaCSASASASTSGSCSCSTSuaccuug B

5417





1141
CAAAGAAGCUCCAAACAAGCAAA
5400
19837
hCLCA1:1141L23 GB3.3


B
uuugcuuGSTSTSTSGSGSASGSCSuucuuug B

5418





1646
GUCAAACAAAGUGGUGCCAUCAU
5401
19841
hCLCA1:1646L23 GB3.3


B
augauggCSASCSCSASCSTSTSTSguuugac B

5419





2464
CAUACCUGGCUGGAUUGAGAAUG
5402
19836
hCLCA1:2464L23 GB3.3


B
cauucucASASTSCSCSASGSCSCSagguaug B

5420





2542
CAAGCAAGUGUGUUUCAGCAGAA
5403
19839
hCLCA1:2542L23 GB3.3


B
uucugcuGSASASASCSASCSASCSuugcuug B

5421





2577
GCUCAUUUGUGGCUUCUGAUGUC
5404
19840
hCLCA1:2577L23 GB3.3


B
gacaucaGSASASGSCSCSASCSASaaugagc B

5422





2711
UAUGACCAUGGAACAGCUCACAA
5405
19842
hCLCA1:2711L23 GB3.3


B
uugugagCSTSGSTSTSCSCSASTSggucaua B

5423





3087
GGAUAGGAGAACUGCAGCUGUCA
5406
19838
hCLCA1:3087L23 GB3.3


B
ugacagcTSGSCSASGSTSTSCSTSccuaucc B

5424





69
TCTTGATTCTTCACC
5407
20960
hCLCA1-69 Rz-7 allyl
gSgSuSgSaag cUGAuGaggccguuaggccGaa Aucaaga B
5425






stab1e





70
CTTGATTCTTCACCT
5408
20961
hCLCA1-70 Rz-7 allyl
aSgSgSuSgaa cUGAuGaggccguuaggccGaa Aaucaag B
5426






stab1e





71
TTGATTCTTCACCTT
5409
20968
hCLCA1-71 CHz-7 allyl
aSaSgSgSuga cUGAuGaggccguuaggccGaa Iaaucaa B
5427






stab1e





72
TGATTCTTCACCTTC
5410
20962
hCLCA1-72 Rz-7 allyl
gSaSaSgSgug cUGAuGaggccguuaggccGaa Agaauca B
5428






stab1e





73
GATTCTTCACCTTCT
5411
20963
hCLCA1-73 Rz-7 allyl
aSgSaSaSggu cUGAuGaggccguuaggccGaa Aagaauc B
5429






stab1e





445
TCCTGATTTCATTGC
5412
20964
hCLCA1-445 Rz-7 allyl
gScSaSaSuga cUGAuGaggccguuaggccGaa Aucagga B
5430






stab1e





446
CCTGATTTCATTGCA
5413
20965
hCLCA1-446 Rz-7 allyl
uSgScSaSaug cUGAuGaggccguuaggccGaa Aaucagg B
5431






stab1e





447
CTGATTTCATTGCAG
5414
20966
hCLCA1-447 Rz-7 allyl
cSuSgScSaau cUGAuGaggccguuaggccGaa Aaaucag B
5432






stab1e





448
TGATTTCATTGCAGG
5415
20969
hCLCA1-448 CHz7
cScSuSgScaa cUGAuGaggccguuaggccGaa Iaaauca B
5433






allyl staB1e





450
ATTTCATTGCAGGAA
5416
20967
hCLCA1-450 Rz-7 allyl
uSuScScSugc cUGAuGaggccguuaggccGaa Augaaau B
5434






stab1e






lower case = 2′OMe; A = riBo A




Upper Case = DeoxyriBose (DNA)




s = phosphorothioate linkages






B
= inverted aBasic









U


 = 2′-C-allyl Uridine







G
= riBo G









[0197]

10





TABLE X










PCR Primers 249.021










PCR primer
Seq ID No














 CGAAATCTCGAGCAGACTTGTGGGAGAAGCTC
5435



AGCACACTGCAGAGTTGCTGGCCAGCTTACCTCC
5436











[0198]


Claims
  • 1. A nucleic acid molecule that down regulates expression of CLCA1 (Chloride Channel Calcium Activated) gene.
  • 2. The nucleic acid molecule of claim 1, wherein said nucleic acid molecule is used to treat conditions selected from the group consisting of Chronic Obstructive Pulmonary Disease (COPD), chronic bronchitis, asthma, cystic fibrosis, and obstructive bowel syndrome.
  • 3. The nucleic acid molecule of claim 1, wherein said nucleic acid molecule is an enzymatic nucleic acid molecule.
  • 4. The nucleic acid molecule of claim 3, wherein a binding arm of said enzymatic nucleic acid molecule comprise sequences complementary to any of sequences having SEQ ID NOs:1-2189 and 5399-5416.
  • 5. The nucleic acid molecule of claim 3, wherein said enzymatic nucleic acid molecule comprises any of sequences having SEQ ID NOs:2190-5398 and 5425-5434.
  • 6. The nucleic acid molecule of claim 1, wherein said nucleic acid molecule is an antisense nucleic acid molecule.
  • 7. The nucleic acid molecule of claim 6, wherein said antisense nucleic acid molecule comprises sequences complementary to any of sequences having SEQ ID NOs:1-2189 and 5399-5416.
  • 8. The nucleic acid molecule of claim 6, wherein said antisense nucleic acid molecule comprise any of sequences having SEQ ID NOs:5417-5424.
  • 9. The nucleic acid molecule of claim 3, wherein said enzymatic nucleic acid molecule is in a hammerhead (HH) motif.
  • 10. The nucleic acid molecule of claim 3, wherein said enzymatic nucleic acid molecule is in a hairpin, hepatitis Delta virus, group I intron, VS nucleic acid, amberzyme, zinzyme or RNAse P nucleic acid motif.
  • 11. The nucleic acid molecule of claim 3, wherein said enzymatic nucleic acid molecule is in an Inozyme motif.
  • 12. The nucleic acid molecule of claim 3, wherein said enzymatic nucleic acid molecule is in a G-cleaver motif.
  • 13. The nucleic acid molecule of claim 3, wherein said enzymatic nucleic acid molecule is a DNAzyme.
  • 14. The nucleic acid molecule of claims 3 or 6, wherein said nucleic acid molecule comprises between 12 and 100 bases complementary to RNA of a CLCA1 gene.
  • 15. The nucleic acid molecule of claims 3 or 6, wherein said nucleic acid molecule comprises between 14 and 24 bases complementary to RNA of a CLCA1 gene.
  • 16. The nucleic acid molecule of claim 1, wherein said nucleic acid molecule is chemically synthesized.
  • 17. The nucleic acid molecule of claim 1, wherein said nucleic acid molecule comprises at least one 2′-sugar modification.
  • 18. The nucleic acid molecule of claim 1, wherein said nucleic acid molecule comprises at least one nucleic acid base modification.
  • 19. The nucleic acid molecule of claim 1, wherein said nucleic acid molecule comprises at least one phosphate backbone modification.
  • 20. A mammalian cell comprising the nucleic acid molecule of claim 1.
  • 21. The mammalian cell of claim 20, wherein said mammalian cell is a human cell.
  • 22. A method of reducing CLCA1 activity in a cell, comprising the step of contacting said cell with the nucleic acid molecule of claim 1, under conditions suitable for said reduction of CLCA1 activity.
  • 23. A method of treatment of a patient having a condition associated with the level of CLCA1, comprising contacting cells of said patient with the nucleic acid molecule of claim 1, under conditions suitable for said treatment.
  • 24. The method of claim 23 further comprising the use of one or more therapies under conditions suitable for said treatment.
  • 25. A method of cleaving RNA of a CLCA1 gene, comprising contacting the nucleic acid molecule of claim 3 with said RNA under conditions suitable for the cleavage of said RNA.
  • 26. The method of claim 25, wherein said cleavage is carried out in the presence of a divalent cation.
  • 27. The method of claim 26, wherein said divalent cation is Mg2+.
  • 28. The nucleic acid molecule of claim 1, wherein said nucleic acid comprises a cap structure, wherein the cap structure is at the 5′-end or 3′-end or both the 5′-end and the 3′-end.
  • 29. The enzymatic nucleic acid molecule of claim 9, wherein said hammerhead motif comprises sequences complementary to any of sequences having SEQ ID NOs: 1-575.
  • 30. The enzymatic nucleic acid molecule of claim 11, wherein said Inozyme motif comprises sequences complementary to any of sequences having SEQ ID NOs:576-1210.
  • 31. The enzymatic nucleic acid molecule of claim 12, wherein said G-cleaver motif comprises sequences complementary to any of sequences having SEQ ID NOs:1211-1429.
  • 32. The enzymatic nucleic acid molecule of claim 13, wherein said DNAzyme comprises sequences complementary to any sequence shown as substrate sequences in Table VII.
  • 33. The enzymatic nucleic acid molecule of claim 10, wherein said zinzyme comprises sequences complementary to any sequence shown as substrate sequences in Table VI.
  • 34. The enzymatic nucleic acid molecule of claim 10, wherein said amberzyme comprises sequences complementary to any sequence shown as substrate sequences in Table VIU.
  • 35. An expression vector comprising at least one nucleic acid molecule of claim 1, in a manner that allows expression of the nucleic acid molecule.
  • 36. A mammalian cell comprising an expression vector of claim 35.
  • 37. The mammalian cell of claim 36, wherein said mammalian cell is a human cell.
  • 38. The expression vector of claim 35, wherein said nucleic acid molecule is an enzymatic nucleic acid molecule.
  • 39. The expression vector of claim 35, wherein said expression vector further comprises an antisense nucleic acid molecule complementary to RNA of a CLCA1 gene.
  • 40. The expression vector of claim 35, wherein said expression vector comprises at least two said nucleic acid molecules.
  • 41. The expression vector of claim 40, wherein the at least two nucleic acid molecules are the same.
  • 42. The expression vector of claim 40, wherein the at least two nucleic acid molecules are different.
  • 43. The expression vector of claim 40, wherein one said expression vector further comprises an antisense nucleic acid molecule complementary to RNA of a CLCA1 gene.
  • 44. The expression vector of claim 40, wherein one said expression vector further comprises an enzymatic nucleic acid molecule complementary to RNA of a CLCA1 gene.
  • 45. A method for treatment of chronic obstructive pulmonary disease comprising the step of administering to a patient the nucleic acid molecule of claim 1 under conditions suitable for said treatment.
  • 46. A method for treatment of cystic fibrosis comprising the step of administering to a patient the nucleic acid molecule of claim 1 under conditions suitable for said treatment.
  • 47. An enzymatic nucleic acid molecule that cleaves RNA derived from a CLCA1 gene.
  • 48. The enzymatic nucleic acid molecule of claim 47, wherein said enzymatic nucleic acid molecule is selected from the group consisting of Hammerhead, Hairpin, Inozyme, G-cleaver, DNAzyme, Amberzyme and Zinzyme.
  • 49. The method of claims 45 or 46, wherein said method further comprises administering to said patient the nucleic acid molecule of claim 1 in conjunction with one or more other therapies.
  • 50. The method of claim 49, wherein said other therapies are therapies selected from the group consisting of oxygen therapy, bronchodilators, corticosteroids, antibacterials, vaccinations, acetylcysteine, mucokinetic agents, and DNase (Pulmozyme) treatments.
  • 51. The nucleic acid molecule of claim 9, wherein said nucleic acid molecule comprises at least five ribose residues, at least ten 2′-O-methyl modifications, and a 3′-end modification.
  • 52. The nucleic acid molecule of claim 51, wherein said nucleic acid molecule further comprises a phosphorothioate core with both 3′ and 5′ -end modifications.
  • 53. The nucleic acid molecule of claims 51 or 52, wherein said 3′ and/or 5′-end modification is 3′-3′ inverted abasic moiety.
  • 54. The nucleic acid molecule of claim 3, wherein said nucleic acid molecule comprises at least five ribose residues; at least ten 2′-O-methyl modifications, and a 3′-end modification.
  • 55. The nucleic acid molecule of claim 54, wherein said nucleic acid molecule further comprises phosphorothioate linkages on at least three of the 5′ terminal nucleotides.
  • 56. The nucleic acid molecule of claim 54, wherein said 3′-end modification is 3′-3′ inverted abasic moiety.
  • 57. The enzymatic nucleic acid molecule of claim 13, wherein said DNAzyme comprises at least ten 2′-O-methyl modifications.
  • 58. The enzymatic nucleic acid molecule of claim 57, wherein said DNAzyme further comprises phosphorothioate linkages on at least three of the 5′ terminal nucleotides.
  • 59. The enzymatic nucleic acid molecule of claim 57, wherein said DNAzyme further comprises a 3′-end modification.
  • 60. The enzymatic nucleic acid molecule of claim 59, wherein said 3′-end modification is 3′-3′ inverted abasic moiety.
Provisional Applications (1)
Number Date Country
60224383 Aug 2000 US