Enzymatic nucleic acid treatment of diseases or conditions related to levels of IKK-gamma and PKR

Abstract

The present invention relates to nucleic acid molecules, including antisense and enzymatic nucleic acid molecules, such as hammerhead ribozymes, DNAzymes, allozymes, aptamers, decoys and siRNA (RNAi), which modulate the expression or function of IKK genes, such as IKK-gamma, IKK-alpha, or IKK-beta, and PKR genes.

Description

[0001] This patent application is a continuation of U.S. Ser. No. 10/156,306, filed May 28, 2002, now allowed, which is a continuation in part of PCT/US02/10512, filed Apr. 3, 2002, and which claims the benefit of U.S. Ser. No. 60/294,412, filed May 29, 2001. These applications are hereby incorporated by reference herein in their entirety including the drawings.

FIELD OF THE INVENTION

[0002] The present invention relates to therapeutic compositions and methods for the treatment or diagnosis of diseases or conditions related to IKK gamma (IKKG) and PKR levels, such as cancer, inflammatory, and autoimmune diseases and/or disorders.

BACKGROUND OF THE INVENTION

[0003] The following is a brief description of the physiological role of nuclear factor kappa B (NFKB), IKK kinases, and protein kinase PKR. The discussion is provided only for understanding the invention that follows. This summary is not an admission that any of the work described below is prior art to the claimed invention.

[0004] Nuclear factor kappa B (NFKB) is a multiunit transcription factor which regulates the expression of genes involved in a number of physiologic and pathologic processes. NFKB is a key component of the TNF signaling pathway. These processes include, but are not limited to: apoptosis, immune, inflammatory and acute phase responses. The REL-A gene product (a.k.a. RelA or p65), and p50 subunits of NFKB, have been implicated in the induction of inflammatory responses and cellular transformation. NFKB exists in the cytoplasm as an inactive heterodimer of the p50 and p65 subunits. NFKB is complexed with an inhibitory protein complex, IkappaB (IKK complex), until activated by the appropriate stimuli. NFKB activation can occur following stimulation of a variety of cell types by inflammatory mediators, for example TNF and IL-1, and reactive oxygen intermediates. In response to induction, NFKB can stimulate production of pro-inflammatory cytokines such as TNF-alpha, IL-1-beta, IL-6 and iNOS, thereby perpetuating a positive feedback loop. NFKB appears to play a role in a number of disease processes including: ischemia/reperfusion injury (CNS and myocardial), glomerulonephritis, sepsis, allergic airway inflammation, inflammatory bowel disease, infection, arthritis, and cancer.

[0005] The nuclear DNA-binding protein, NFKB, was first identified as a factor that binds and activates the immunoglobulin kappa light chain enhancer in B cells. NFKB now is known to activate transcription of a variety of other cellular genes (e.g., cytokines, adhesion proteins, oncogenes and viral proteins) in response to a variety of stimuli (e.g., phorbol esters, mitogens, cytokines and oxidative stress). In addition, molecular and biochemical characterization of NFKB has shown that the activity is due to a homodimer or heterodimer of a family of DNA binding subunits. Each subunit bears a stretch of 300 amino acids that is homologous to the oncogene, v-rel. The activity first described as NFKB is a heterodimer of p49 or p50 with p65. The p49 and p50 subunits of NFKB (encoded by the NF-kappa B2 or NF kappa B1 genes, respectively) are generated from the precursors NFKB1 (p105) or NFKB2 (p100). The p65 subunit of NFKB (now termed REL-A) is encoded by the rel-A locus.

[0006] The roles of each specific transcription-activating complex now are being elucidated in cells (Perkins, et al., 1992, Proc. Natl. Acad. Sci USA, 89, 1529-1533). For instance, the heterodimer of NFKB1 and Rel A (p50/p65) activates transcription of the promoter for the adhesion molecule, VCAM-1, while NFKB2/RelA heterodimers (p49/p65) actually inhibit transcription (Shu, et al., 1993, Mol. Cell. Biol., 13, 6283-6289). Conversely, heterodimers of NFKB2/RelA (p49/p65) act with Tat-I to activate transcription of the HIV genome, while NFKB1/RelA (p50/p65) heterodimers have little effect (Liu et al., 1992, J. Virol., 3883-3887). Similarly, blocking rel A gene expression with antisense oligonucleotides specifically blocks embryonic stem cell adhesion; blocking NFKB1 gene expression with antisense oligonucleotides had no effect on cellular adhesion (Narayanan et al., 1993, Mol. Cell. Biol., 13, 3802-3810). Thus, the promiscuous role initially assigned to NFKB in transcriptional activation (Lenardo, and Baltimore, 1989, Cell, 58, 227-229) represents the sum of the activities of the rel family of DNA-binding proteins. This conclusion is supported by recent transgenic "knock-out" mice of individual members of the rel family. Such "knock-outs" show few developmental defects, suggesting that essential transcriptional activation functions can be performed by more than one member of the rel family.

[0007] A number of specific inhibitors of NFKB function in cells exist, including treatment with phosphorothioate antisense oliogonucleotide, treatment with double-stranded NFKB binding sites, and over expression of the natural inhibitor MAD-3 (an Ikappa-B family member). These agents have been used to show that NFKB is required for induction of a number of molecules involved in cancer and/or inflammation, as described below.

[0008] NFkB is required for phorbol ester-mediated induction of IL-6 (Kitajima, et al., 1992, Science, 258, 1792-5) and IL-8 (Kunsch and Rosen, 1993, Mol. Cell. Biol., 13, 6137-46).

[0009] NFkB is required for induction of the adhesion molecules ICAM-1 (Eck, et al., 1993, Mol. Cell. Biol., 13, 6530-6536), VCAM-1 (Shu et al., supra), and E-selectin (Read, et al., 1994, J. Exp. Med., 179, 503-512) on endothelial cells.

[0010] NFkB is involved in the induction of the integrin subunit, CD18, and other adhesive properties of leukocytes (Eck et al., 1993 supra).

[0011] HER2/Neu overexpression induces NFKB via a PI3-kinase/Akt pathway involving calpain-mediated degradation of IKB-alpha. Breast cancer has been shown to typify the aberrant expression of NFKB/REL factors (Pianetti et al., 2001, Oncogene, 20, 1287-1299; Sovak et al., 1999, J. Clin. Invest., 100, 2952-2960).

[0012] Inhibition of NFKB activity has been shown to induce apoptosis in murine hepatocytes (Bellas et al., 1997, Am. J. Pathol., 151, 891-896).

[0013] NFKB has been shown to regulate cyclooxygenase-2 expression and cell proliferation in human gastric cancer cells (Joo Weon et al., 2001, Laboratory Investigation, 81, 349-360).

[0014] The above studies suggest that NFKB is integrally involved in the induction of cytokines and adhesion molecules by inflammatory mediators and is involved in the transformation of cancerous cells. Two reported studies point to another connection between NFKB and inflammation: glucocorticoids can exert their anti-inflammatory effects by inhibiting NFKB. The glucocorticoid receptor and p65 both act at NFKB binding sites in the ICAM-1 promoter (van de Stolpe, et al., 1994, J. Biol. Chem., 269, 6185-6192). Glucocorticoid receptor inhibits NFKB-mediated induction of IL-6 (Ray and Prefontaine, 1994 Proc. Natl. Acad. Sci USA, 91, 752-756). Conversely, overexpression of p65 inhibits glucocorticoid induction of the mouse mammary tumor virus promoter. Finally, protein cross-linking and co-immunoprecipitation experiments demonstrated direct physical interaction between p65 and the glucocorticoid receptor.

[0015] The IKK complex that sequesters NFKB in the cytoplasm comprises IkappaB (I.kappa.B) proteins (I.kappa.B-alpha, I.kappa.B-beta, I.kappa.B-epsilon, p105, and p100). The phosphorylation of I.kappa.B proteins results in the release of NFKB from the I.kappa.B complex which is transported to the nucleus via the unmasking of nuclear translocation signals. Phosphorylation marks IkB proteins for ubiquitination and degradation via the proteosome pathway. Most NFKB inducing stimuli initiate activation of an I.kappa.B kinase (IKK) complex that contains two catalytic subunits, IKK -alpha (IKK1) and IKK-beta (IKK2), that phosphorylate I.kappa.B-alpha and I.kappa.B-beta, with IKK-beta playing a predominant role in pro-inflammatory signaling. In addition to the two kinases, the IKK complex contains regulatory subunits, including IKK-gamma (NEMO/IKKAP1). IKK-gamma is a protein that is critical for the assembly of the IKK complex. IKK-gamma directly binds to IKK-beta and is required for activation of NFKB, for example by TNF-alpha, IL-1-beta, lipopolysaccharide, phorbol 12-myristate 13-acetate, the human T-cell lymphotrophic virus (HTLV-1), or double stranded RNA. Genomic rearrangements in IKK-gamma have been shown to impair NFKB activation and result in incontinentia pigmenti. Additional proteins that associate with the IKK complex include, MEK kinase (MEKK1), NFKB inducing kinase (NIK), receptor interacting protein (RIP), protein kinase CK2, and IKK-associated protein (IKAP), which appears to be associated with the I.kappa.B Kinase (IKK) complex, but does not appear to be an integral component of the tripartate IKK complex as does IKK-gamma (Krappmann et al., 2001, J. Biol. Chem., 275, 29779-87).

[0016] The RNA-dependent protein kinase PKR is a signal transducer for NFKB and IFN regulatory factor-1. PKR is required for activation of NFKB by IFN-gamma via a STAT-1 independent pathway (Amitabha et al., 2001, J. Immunol., 166, 6170-6180). The induction of NFKB by PKR takes place though phosphorylation of I.kappa.B-alpha, and appears not to require the catalytic activity of PKR, thereby proceeding independently of the dsRNA-binding properties of PKR (Ishii et al., 2001, Oncogene, 20, 1900-1912). PKR also plays an important role in the regulation of protein synthesis by modulating the activity of eukaryotic initiation factor 2 (eIF-2-alpha) through interferon induction.

[0017] Kamiya, JP 2000253884, describes specific antisense oligonucleotides for inhibiting I.kappa.B-kinase subunit expression. Krappmann et al., 2001, J. Biol. Chem., describe specific antisense oligonucleotides to IKK-gamma.

SUMMARY OF THE INVENTION

[0018] The present invention features a nucleic acid molecule, such as decoy RNA, dsRNA, siRNA, aptamers, antisense nucleic acid molecules, and enzymatic nucleic acid molecule which down regulates expression of a sequence encoding an IkappaB kinase (IKK) subunit. The invention also features an enzymatic nucleic acid molecule which down regulates expression of a sequence encoding protein kinase PKR.

[0019] In one embodiment, an enzymatic nucleic acid molecule of the invention comprises a sequence selected from the group consisting of SEQ ID NOs. 632-1261, 1762-2260, 2480-2698, 2904-3485, 3814-4360, 4555-4748, 5253-5756, 6034-6310, 6380-6789, 7142-7770, and 7884-8001.

[0020] In another embodiment, an enzymatic nucleic acid molecule of the invention comprises at least one binding arm wherein one or more of said binding arms comprises a sequence complementary to a sequence selected from the group consisting of SEQ ID NOs. 1-631, 1263-1761, 2261-2479, 2699-2903, 3486-3813, 4361-4554, 4749-5252, 5757-6033, 6311-6379, 6790-7141, and 7771-7883.

[0021] In another embodiment, an antisense nucleic acid molecule of the invention comprises a sequence complementary to a sequence selected from the group consisting of SEQ ID NOs. 1-631, 1263-1761, 2261-2479, 2699-2903, 3486-3813, 4361-4554, 4749-5252, 5757-6033, 6311-6379, 6790-7141, and 7771-7883.

[0022] In another embodiment, an nucleic acid molecule of the invention is adapted to treat cancer. In yet another embodiment, an enzymatic nucleic acid molecule of the invention has an endonuclease activity to cleave RNA having IKK-gamma or PKR nucleic acid sequence.

[0023] In one embodiment, an enzymatic nucleic acid molecule of the invention is in an Inozyme, Zinzyme, G-cleaver, Amberzyme, DNAzyme, or Hammerhead configuration.

[0024] In another embodiment, an Inozyme of the invention comprises a sequence complementary to a sequence selected from the group consisting of SEQ ID NOs. 1263-1761, 4749-5252, 7781-7787, 7796-7800, 7822-7846, and 7866-7870.

[0025] In another embodiment, an Inozyme of the invention comprises a sequence selected from the group consisting of SEQ ID NOs. 1762-2260, 5253-5756, 7894-7900, 7909-7913, 7938-7962, and 7982-7986.

[0026] In another embodiment, a Zinzyme of the invention comprises a sequence complementary to a sequence selected from the group consisting of SEQ ID NOs. 2261-2479, 5757-6033, 7788-7790, 7847-7860, and 7871-7895.

[0027] In another embodiment, a Zinzyme of the invention comprises a sequence selected from the group consisting of SEQ ID NOs 2480-2698, 6034-6310, 7901-7903, 7963-7976, and 7987-7991.

[0028] In another embodiment, an Amberzyme of the invention comprises a sequence selected from the group consisting of SEQ ID NOs 3814-4360, 7142-7770, 7924-7928, and 7997-8001.

[0029] In another embodiment, a DNAzyme of the invention comprises a sequence selected from the group consisting of SEQ ID NOs 2904-3485, 6380-6789, 7919-7923, and 7992-7996.

[0030] In another embodiment, a Hammerhead of the invention comprises a sequence complementary to a sequence selected from the group consisting of SEQ ID NOs. 1-631, 4361-4554, 7771-7780, 7791-7795, 7813-7821, and 7861-7865.

[0031] In another embodiment, a Hammerhead of the invention comprises a sequence selected from the group consisting of SEQ ID NOs 632-1262, 4555-4748, 7884-7894, 7904-7908, 7929-7937, 7977-7981.

[0032] In one embodiment, a nucleic acid molecule of the invention comprises between 12 and 100 bases complementary to RNA having an IKK-gamma or PKR nucleic acid sequence. In another embodiment, a nucleic acid molecule of the invention comprises between 14 and 24 bases complementary to RNA having an IKK-gamma or PKR nucleic acid sequence.

[0033] In yet another embodiment, a nucleic acid molecule of the invention is chemically synthesized.

[0034] In another embodiment, a nucleic acid molecule or antisense nucleic acid molecule of the invention comprises at least one 2'-sugar modification, at least one nucleic acid base modification, or at least one phosphate backbone modification.

[0035] In one embodiment, a siRNA molecule of the invention comprises a double stranded RNA wherein one strand of the RNA is complimentary to the RNA of IKK-gamma or PKR gene.

[0036] In another embodiment, a siRNA molecule of the invention comprises a double stranded RNA wherein one strand of the RNA comprises a portion of a sequence of RNA having IKK-gamma or PKR gene sequence. In yet another embodiment, a siRNA molecule of the invention comprises a double stranded RNA wherein both strands of RNA are connected by a non-nucleotide linker. Alternately, a siRNA molecule of the invention comprises a double stranded RNA wherein both strands of RNA are connected by a nucleotide linker, such as a loop or stem loop structure.

[0037] In one embodiment, a single strand component of a siRNA molecule of the invention is from about 14 to about 50 nucleotides in length. In another embodiment, a single strand component of a siRNA molecule of the invention is about 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, or 28 nucleotides in length. In yet another embodiment, a single strand component of a siRNA molecule of the invention is about 23 nucleotides in length. In one embodiment, a siRNA molecule of the invention is from about 28 to about 56 nucleotides in length. In another embodiment, a siRNA molecule of the invention is about 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, or 52 nucleotides in length. In yet another embodiment, a siRNA molecule of the invention is about 46 nucleotides in length.

[0038] In another embodiment, an enzymatic nucleic acid molecule, antisense nucleic acid molecule, decoy RNA, dsRNA, siRNA, or aptamer molecules of the invention comprises at least one 2'-sugar modification.

[0039] In another embodiment, an enzymatic nucleic acid molecule, antisense nucleic acid molecule, decoy RNA, dsRNA, siRNA, or aptamer, nucleic acids of the invention comprises at least one nucleic acid base modification.

[0040] In another embodiment, an enzymatic nucleic acid molecule, antisense nucleic acid molecule, decoy RNA, dsRNA, siRNA, or aptamer, nucleic acids of the invention comprises at least one phosphate backbone modification.

[0041] In one embodiment, the invention features a mammalian cell, for example a human cell, including an nucleic acid molecule of the invention.

[0042] The present invention features method of down-regulating PKR activity in a cell, comprising contacting the cell with an enzymatic nucleic acid molecule or antisense nucleic acid molecule, or other nucleic acid molecule of the invention, under conditions suitable for down-regulating of PKR activity.

[0043] The present invention also features method of treatment of a subject having a condition associated with the level of PKR, comprising contacting cells of the subject with an enzymatic nucleic acid molecule or antisense nucleic acid molecule or other nucleic acid molecule of the invention under conditions suitable for the treatment.

[0044] The present invention features method of down-regulating IKK-gamma activity in a cell, comprising contacting the cell with an enzymatic nucleic acid molecule or antisense nucleic acid molecule or other nucleic acid molecule of the invention, under conditions suitable for down-regulating of IKK-gamma activity.

[0045] The present invention also features method of treatment of a subject having a condition associated with the level of IKK-gamma, comprising contacting cells of the subject with the enzymatic nucleic acid molecule or antisense nucleic acid molecule or other nucleic acid molecule of the invention, under conditions suitable for the treatment.

[0046] In one embodiment, a method of treatment of the invention comprises the use of one or more drug therapies under conditions suitable for said treatment.

[0047] The present invention features methods of cleaving RNA comprising a PKR nucleic acid sequence comprising contacting an enzymatic nucleic acid molecule of the invention with the RNA under conditions suitable for the cleavage.

[0048] The present invention also features methods of cleaving RNA comprising a IKK-gamma nucleic acid sequence comprising contacting an enzymatic nucleic acid molecule of the invention with the RNA under conditions suitable for the cleavage.

[0049] In one embodiment, a method of cleavage of the invention is carried out in the presence of a divalent cation, for example Mg2+.

[0050] In another embodiment, an enzymatic nucleic acid or antisense nucleic acid molecule or other nucleic acid molecule of the invention 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, for example a 3',3'-linked or 5',5'-linked deoxyabasic derivative.

[0051] The present invention also features an expression vector comprising a nucleic acid sequence encoding at least one enzymatic nucleic acid molecule, antisense, or other nucleic acid molecule of the invention in a manner which allows expression of the nucleic acid molecule.

[0052] In one embodiment, the invention features a mammalian cell, for example a human cell, including an expression vector contemplated by the invention.

[0053] In another embodiment, an expression vector of the invention further comprises an antisense nucleic acid molecule complementary to RNA of a subunit of IKK-gamma or PKR.

[0054] In yet another embodiment, an expression vector of the invention comprises a nucleic acid sequence encoding two or more enzymatic nucleic acid molecules, which can be the same or different.

[0055] The present invention also features a method for treatment of cancer, for example breast cancer, lung cancer, prostate cancer, colorectal cancer, brain cancer, esophageal cancer, stomach cancer, bladder cancer, pancreatic cancer, cervical cancer, head and neck cancer, ovarian cancer, melanoma, lymphoma, glioma, or multidrug resistant cancer, comprising administering to a subject an enzymatic nucleic acid molecule or antisense nucleic acid molecule or other nucleic acid molecule of the invention under conditions suitable for said treatment.

[0056] In one embodiment, a nucleic acid molecule of the invention comprises at least five ribose residues, at least ten 2'-O-methyl modifications, and a 3'-end modification such as a 3'-3' inverted abasic moiety, and/or phosphorothioate linkages on at least three of the 5' terminal nucleotides.

[0057] In another embodiment, other drug therapies contemplated by the invention include monoclonal antibodies, IKK-gamma or PKR-specific inhibitors, chemotherapy, or radiation therapy.

[0058] Specific chemotherapy contemplated by the invention include paclitaxel, docetaxel, cisplatin, methotrexate, cyclophosphamide, 5-fluoro uridine, Leucovorin, Irinotecan (CAMPTOSAR.RTM. or CPT-11 or Camptothecin-11 or Campto), Paclitaxel, Carboplatin doxorubin, fluorouracil carboplatin, edatrexate, gemcitabine, or vinorelbine or a combination thereof.

[0059] The invention also features a method for treatment of an inflammatory disease, for example rheumatoid arthritis, restenosis, asthma, Crohn's disease, diabetes, obesity, autoimmune disease, lupus, multiple sclerosis, transplant/graft rejection, gene therapy applications, ischemia/reperfusion injury, glomerulonephritis, sepsis, allergic airway inflammation, inflammatory bowel disease, or infection, comprising the step of administering to a subject an enzymatic nucleic acid or antisense nucleic acid molecule of the invention under conditions suitable for the treatment.

[0060] The present invention features compositions comprising the enzymatic nucleic acid and/or antisense nucleic acid molecules of the invention in a pharmaceutically acceptable carrier.

[0061] The invention also features a method of administering to a cell, such as mammalian cell (e.g. human cell), where the cell can be in culture or in a mammal, such as a human, an enzymatic nucleic acid molecule or antisense molecule of the instant invention, comprising contacting the cell with the enzymatic nucleic acid molecule or antisense molecule or other nucleic acid molecule of the invention under conditions suitable for such administration. The method of administration can be in the presence of a delivery reagent, for example a lipid, cationic lipid, phospholipid, or liposome.

DETAILED DESCRIPTION OF THE INVENTION

[0062] First the drawings will be described briefly.

DRAWINGS

[0063] FIG. 1 shows examples of chemically stabilized ribozyme motifs. HH Rz, 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, Eckstein et al., International PCT publication No. WO 99/16871). N or n, represent independently a nucleotide which can 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.

[0064] 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).

[0065] FIG. 3 shows an example of the Zinzyme A ribozyme motif that is chemically stabilized (see for example Beigelman et al., Beigelman et al, International PCT publication No. WO 99/55857).

[0066] FIG. 4 shows an example of a DNAzyme motif described by Santoro et al., 1997, PNAS, 94, 4262.

[0067] The invention features nucleic acid molecules, for example enzymatic nucleic acid molecules, antisense nucleic acid molecules, 2,5-A chimeras, decoys, double stranded RNA, triplex oligonucleotides, and/or aptamers, and methods to modulate gene expression, for example, genes encoding a member of the I.kappa.B kinase IKK complex, such as IKK-alpha (IKK1), IKK-beta (IKK2), or IKK-gamma (IKK.gamma.) and/or a protein kinase PKR protein. In particular, the instant invention features nucleic-acid based molecules and methods to modulate the expression of IKK-gamma (IKK.gamma.) and protein kinase PKR.

[0068] The invention features one or more enzymatic nucleic acid-based molecules and methods that independently or in combination modulate the expression of gene(s) encoding a member of the I.kappa.B kinase IKK complex or PKR. In particular embodiments, the invention features nucleic acid-based molecules and methods that modulate the expression of a member of the I.kappa.B kinase IKK complex, for example IKK-alpha (IKK1), IKK-beta (IKK2), or IKK-gamma (IKK.gamma.) and/or a protein kinase PKR protein, such as IKK-alpha (IKK1) gene (Genbank Accession No. NM.sub.--001278); IKK-beta (IKK2) gene, for example (Genbank Accession No.AF080158), IKK-gamma (IKK.gamma.) gene, for example (Genbank Accession No. NM.sub.--003639), and protein kinase PKR gene, for example (Genbank Accession No. NM.sub.--002759).

[0069] The description below of the various aspects and embodiments is provided with reference to the exemplary IKK-gamma and PKR genes. IKK-gamma is also known as NEMO/IKKAP1. However, the various aspects and embodiments are also directed to other genes which encode other subunits of the IKK complex, such as IKK-alpha (IKK1) or IKK-beta (IKK2). Those additional genes can be analyzed for target sites using the methods described for IKK-gamma or PKR. Thus, the inhibition and the effects of such inhibition of the other genes can be performed as described herein.

[0070] In one embodiment, the invention features the use of an enzymatic nucleic acid molecule, preferably in the hammerhead, NCH, G-cleaver, amberzyme, zinzyme and/or DNAzyme motif, to down-regulate the expression of IKK-gamma or PKR genes.

[0071] By "inhibit" or "down-regulate" it is meant that the expression of the gene, or level of RNAs or equivalent RNAs encoding one or more protein subunits, or activity of one or more protein subunits, such as IKK-gamma or PKR subunit(s), is reduced below that observed in the absence of the nucleic acid molecules of the invention. In one embodiment, inhibition or down-regulation with enzymatic nucleic acid molecule 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 or down-regulation 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 or down-regulation of IKK-gamma or PKR with the nucleic acid molecule of the instant invention is greater in the presence of the nucleic acid molecule than in its absence.

[0072] By "up-regulate" is meant that the expression of the gene, or level of RNAs or equivalent RNAs encoding one or more protein subunits, or activity of one or more protein subunits, such as IKK-gamma or PKR subunit(s), is greater than that observed in the absence of the nucleic acid molecules of the invention. For example, the expression of a gene, such as IKK-gamma or PKR gene, can be increased in order to treat, prevent, ameliorate, or modulate a pathological condition caused or exacerbated by an absence or low level of gene expression.

[0073] By "modulate" is meant that the expression of the gene, or level of RNAs or equivalent RNAs encoding one or more protein subunits, or activity of one or more protein subunit(s) is up-regulated or down-regulated, such that the expression, level, or activity is greater than or less than that observed in the absence of the nucleic acid molecules of the invention.

[0074] 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% can also be useful in this invention (see for example Werner and Uhlenbeck, 1995, Nucleic Acids Research, 23, 2092-2096; Hammann et al., 1999, Antisense and Nucleic Acid Drug Dev., 9, 25-31). The nucleic acids can 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 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 nucleic acid regions, and that it have nucleotide sequences within or surrounding that substrate binding site which impart a nucleic acid cleaving and/or ligation activity to the molecule (Cech et al., U.S. Pat. No. 4,987,071; Cech et al., 1988, 260 JAMA 3030).

[0075] Several varieties of enzymatic RNAs 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.

[0076] By "nucleic acid molecule" as used herein is meant a molecule having nucleotides. The nucleic acid can be single, double, or multiple stranded and can comprise modified or unmodified nucleotides or non-nucleotides or various mixtures and combinations thereof.

[0077] 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).

[0078] By "substrate binding arm" or "substrate binding domain" is meant that portion/region of a enzymatic nucleic acid which is able to interact, for example via complementarity (i.e., able to base-pair with), with a portion of its substrate. Preferably, such complementarity is 100%, but can be less if desired. For example, as few as 10 bases out of 14 can be base-paired (see for example Werner and Uhlenbeck, 1995, Nucleic Acids Research, 23, 2092-2096; Hammann et al., 1999, Antisense and Nucleic Acid Drug Dev., 9, 25-31). Examples of such arms are shown generally in FIGS. 1-4. That is, these arms contain sequences within a enzymatic nucleic acid which are intended to bring enzymatic nucleic acid and target RNA together through complementary base-pairing interactions. The enzymatic nucleic acid of the invention can have binding arms that are contiguous or non-contiguous and can be of varying lengths. The length of the binding arm(s) are preferably greater than or equal to three nucleotides and of sufficient length to stably interact with the target RNA; preferably 12-100 nucleotides; more preferably 14-24 nucleotides long (see for example Werner and Uhlenbeck, supra; Hamman et al., supra; Hampel et al., EP0360257; Berzal-Herranz et al., 1993, EMBO J., 12, 2567-73). 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, or 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).

[0079] By "Inozyme" or "NCH" motif or configuration is meant, an enzymatic nucleic acid molecule comprising a motif as is generally described as NCH Rz in FIG. 1. Inozymes possess endonuclease activity to cleave RNA substrates having a cleavage triplet NCH/, where N is a nucleotide, C is cytidine and H is adenosine, uridine or cytidine, and/represents the cleavage site. H is used interchangeably with X. Inozymes can also possess endonuclease activity to cleave RNA substrates having a cleavage triplet NCN/, where N is a nucleotide, C is cytidine, and/represents the cleavage site. "I" in FIG. 1 represents an Inosine nucleotide, preferably a ribo-Inosine or xylo-Inosine nucleoside.

[0080] By "G-cleaver" motif or configuration is meant, an enzymatic nucleic acid molecule comprising a motif as is generally described as G-cleaver Rz in FIG. 1. G-cleavers possess endonuclease activity to cleave RNA substrates having a cleavage triplet NYN/, where N is a nucleotide, Y is uridine or cytidine and/represents the cleavage site. G-cleavers can be chemically modified as is generally shown in FIG. 1.

[0081] By "amberzyme" motif or configuration is meant, an enzymatic nucleic acid molecule comprising a motif as is generally described in FIG. 2. Amberzymes possess endonuclease activity to cleave RNA substrates having a cleavage triplet NG/N, where N is a nucleotide, G is guanosine, and/represents the cleavage site. Amberzymes can be chemically modified to increase nuclease stability through substitutions as are generally shown in FIG. 2. In addition, differing nucleoside and/or non-nucleoside linkers can be used to substitute the 5'-gaaa-3' loops shown in the figure. 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.

[0082] By "zinzyme" motif or configuration is meant, an enzymatic nucleic acid molecule comprising a motif as is generally described in FIG. 3. Zinzymes possess endonuclease activity to cleave RNA substrates having a cleavage triplet including but not limited to YG/Y, where Y is uridine or cytidine, and G is guanosine and/represents the cleavage site. Zinzymes can be chemically modified to increase nuclease stability through substitutions as are generally shown in FIG. 3, including substituting 2'-O-methyl guanosine nucleotides for guanosine nucleotides. In addition, differing nucleotide and/or non-nucleotide linkers can be used to substitute the 5'-gaaa-2' loop shown in the figure. 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.

[0083] By `DNAzyme` is meant, an enzymatic nucleic acid molecule that does not require the presence of a 2'-OH group within its own nucleic acid sequence for activity. In particular embodiments the enzymatic nucleic acid molecule can have an attached linker(s) or other attached or associated groups, moieties, or chains containing one or more nucleotides with 2'-OH groups. DNAzymes can be synthesized chemically or expressed endogenously in vivo, by means of a single stranded DNA vector or equivalent thereof. An example of a DNAzyme is shown in FIG. 4 and is generally reviewed in Usman et al., U.S. Pat. No. 6,159,714; Chartrand et al., 1995, NAR 23, 4092; Breaker et al., 1995, Chem. Bio. 2, 655; Santoro et al., 1997, PNAS 94, 4262; Breaker, 1999, Nature Biotechnology, 17, 422-423; and Santoro et. al., 2000, J. Am. Chem. Soc., 122, 2433-39. Additional DNAzyme motifs can be selected for using techniques similar to those described in these references, and hence, are within the scope of the present invention.

[0084] 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 of the nucleic acid molecule.

[0085] 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) that is sufficient to the intended purpose (e.g., cleavage of target RNA by an enzyme).

[0086] By "equivalent" or "related" RNA to IKK-gamma is meant to include those naturally occurring RNA molecules having homology (partial or complete) to IKK-gamma proteins or encoding for proteins with similar function as IKK-gamma proteins 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.

[0087] By "equivalent" or "related" RNA to PKR is meant to include those naturally occurring RNA molecules having homology (partial or complete) to PKR proteins or encoding for proteins with similar function as PKR proteins 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.

[0088] By "homology" is meant the nucleotide sequence of two or more nucleic acid molecules is partially or completely identical.

[0089] 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 Science 261, 1004 and Woolf et al., U.S. Pat. No. 5,849,902). Typically, antisense molecules are complementary to a target sequence along a single contiguous sequence of the antisense molecule. However, in certain embodiments, an antisense molecule can bind to substrate such that the substrate molecule forms a loop, and/or an antisense molecule can bind such that the antisense molecule forms a loop. Thus, the antisense molecule can be complementary to two (or even more) non-contiguous substrate sequences or two (or even more) non-contiguous sequence portions of an antisense molecule can 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, 2000, Methods Enzymol., 313, 3-45; 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. The antisense oligonucleotides can comprise one or more RNAse H activating region, which is capable of activating RNAse H cleavage of a target RNA. Antisense DNA can be synthesized chemically or expressed via the use of a single stranded DNA expression vector or equivalent thereof.

[0090] By "RNase H activating region" is meant a region (generally greater than or equal to 4-25 nucleotides in length, preferably from 5-11 nucleotides in length) of a nucleic acid molecule capable of binding to a target RNA to form a non-covalent complex that is recognized by cellular RNase H enzyme (see for example Arrow et al., U.S. Pat. No. 5,849,902; Arrow et al., U.S. Pat. No. 5,989,912). The RNase H enzyme binds to the nucleic acid molecule-target RNA complex and cleaves the target RNA sequence. The RNase H activating region comprises, for example, phosphodiester, phosphorothioate (preferably at least four of the nucleotides are phosphorothiote substitutions; more specifically, 4-11 of the nucleotides are phosphorothiote substitutions); phosphorodithioate, 5'-thiophosphate, or methylphosphonate backbone chemistry or a combination thereof. In addition to one or more backbone chemistries described above, the RNase H activating region can also comprise a variety of sugar chemistries. For example, the RNase H activating region can comprise deoxyribose, arabino, fluoroarabino or a combination thereof, nucleotide sugar chemistry. Those skilled in the art will recognize that the foregoing are non-limiting examples and that any combination of phosphate, sugar and base chemistry of a nucleic acid that supports the activity of RNase H enzyme is within the scope of the definition of the RNase H activating region and the instant invention.

[0091] By "2-5A chimera" is meant an oligonucleotide, for example an antisense nucleic acid molecule or enzymatic nucleic acid molecule, 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; Silverman et al., 2000, Methods Enzymol., 313, 522-533; Player and Torrence, 1998, Pharmacol. Ther., 78, 55-113).

[0092] By "triplex forming oligonucleotides" or "triplex oligonucleotide" 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; Fox, 2000, Curr. Med. Chem., 7, 17-37; Praseuth et. al., 2000, Biochim. Biophys. Acta, 1489, 181-206).

[0093] By "double stranded RNA" or "dsRNA" is meant a double stranded RNA that matches a predetermined gene sequence that is capable of activating cellular enzymes that degrade the corresponding messenger RNA transcripts of the gene. These dsRNAs are referred to as short intervening RNA (siRNA) and can be used to inhibit gene expression (see for example Elbashir et al., 2001, Nature, 411, 494-498; and Bass, 2001, Nature, 411, 428-429). The term "double stranded RNA" or "dsRNA" as used herein refers to a double stranded RNA molecule capable of RNA interference "RNAi", including short interfering RNA "siRNA" see for example Bass, 2001, Nature, 411, 428-429; Elbashir et al., 2001, Nature, 411, 494-498; and Kreutzer et al., International PCT Publication No. WO 00/44895; Zernicka-Goetz et al., International PCT Publication No. WO 01/36646; Fire, International PCT Publication No. WO 99/32619; Plaetinck et al., International PCT Publication No. WO 00/01846; Mello and Fire, International PCT Publication No. WO 01/29058; Deschamps-Depaillette, International PCT Publication No. WO 99/07409; and Li et al., International PCT Publication No. WO 00/44914.

[0094] By "gene" it is meant a nucleic acid that encodes an RNA, for example, nucleic acid sequences including but not limited to structural genes encoding a polypeptide.

[0095] "Complementarity" refers to the ability of a nucleic acid to 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., enzymatic nucleic acid 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, CSH Symp. 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.

[0096] By "RNA" is meant a molecule comprising at least one ribonucleotide residue. By "ribonucleotide" or "2'-OH" is meant a nucleotide with a hydroxyl group at the 2' position of a .beta.-D-ribo-furanose moiety.

[0097] By "decoy" is meant a nucleic acid molecule, for example RNA or DNA, or aptamer that is designed to preferentially bind to a predetermined ligand. Such binding can result in the inhibition or activation of a target molecule. The decoy or aptamer can compete with a naturally occurring binding target for the binding of a specific ligand. For example, it has been shown that over-expression of HIV trans-activation response (TAR) RNA can act as a "decoy" and efficiently binds HIV tat protein, thereby preventing it from binding to TAR sequences encoded in the HIV RNA (Sullenger et al., 1990, Cell, 63, 601-608). This is but a specific example and those in the art will recognize that other embodiments can be readily generated using techniques generally known in the art, see for example Gold et al., 1995, Annu. Rev. Biochem., 64, 763; Brody and Gold, 2000, J. Biotechnol., 74, 5; Sun, 2000, Curr. Opin. Mol. Ther., 2, 100; Kusser, 2000, J. Biotechnol., 74, 27; Hermann and Patel, 2000, Science, 287, 820; and Jayasena, 1999, Clinical Chemistry, 45, 1628. Similarly, a decoys can be designed to bind to IKK-gamma or PKR and block the binding of IKK-gamma or PKR or a decoy can be designed to bind to IKK-gamma or PKR and prevent interaction with the IKK-gamma or PKR protein.

[0098] By "aptamer" or "nucleic acid aptamer" as used herein is meant a nucleic acid molecule that binds specifically to a target molecule wherein the nucleic acid molecule has sequence that is distinct from sequence recognized by the target molecule in its natural setting. Alternately, an aptamer can be a nucleic acid molecule that binds to a target molecule where the target molecule does not naturally bind to a nucleic acid. The target molecule can be any molecule of interest. For example, the aptamer can be used to bind to a ligand binding domain of a protein, thereby preventing interaction of the naturally occurring ligand with the protein. Similarly, the nucleic acid molecules of the instant invention can bind to IKK-gamma or PKR to block activity of the respective proteins. This is a non-limiting example and those in the art will recognize that other embodiments can be readily generated using techniques generally known in the art, see for example Gold et al., U.S. Pat. Nos. 5,475,096 and 5,270,163; Gold et al., 1995, Annu. Rev. Biochem., 64, 763; Brody and Gold, 2000, J. Biotechnol., 74, 5; Sun, 2000, Curr. Opin. Mol. Ther., 2, 100; Kusser, 2000, J. Biotechnol., 74, 27; Hermann and Patel, 2000, Science, 287, 820; and Jayasena, 1999, Clinical Chemistry, 45, 1628.

[0099] The enzymatic nucleic acid molecule, antisense nucleic acid or other nucleic acid molecules of the invention that down regulate IKK-gamma or PKR gene expression represent a therapeutic approach to treat a variety of inflammatory-related diseases and conditions, including but not limited to rheumatoid arthritis, restenosis, asthma, Crohn's disease, incontinentia pigmenti, diabetes, obesity, autoimmune disease, lupus, multiple sclerosis, transplant/graft rejection, gene therapy applications, ischemia/reperfusion injury (CNS and myocardial), glomerulonephritis, sepsis, allergic airway inflammation, inflammatory bowel disease, infection, and any other inflammatory disease or condition which respond to the modulation of IKK-gamma or PKR function.

[0100] The enzymatic nucleic acid molecule, antisense nucleic acid or other nucleic acid molecules of the invention that down regulate IKK-gamma or PKR gene expression also represent a therapeutic approach to treat a variety of cancers, including but not limited to breast, lung, prostate, colorectal, brain, esophageal, bladder, pancreatic, cervical, head and neck, and ovarian cancer, melanoma, lymphoma, glioma, multidrug resistant cancers, and/or other cancers which respond to the modulation of IKK-gamma or PKR function.

[0101] In one embodiment of the inventions described herein, the enzymatic nucleic acid molecule is formed in a hammerhead or hairpin motif, but can 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; of hairpin motifs 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, and Hampel et al., 1990 Nucleic Acids Res. 18, 299; Chowrira & McSwiggen, U.S. Pat. No. 5,631,359; of the hepatitis delta virus motif is described by Perrotta and Been, 1992 Biochemistry 31, 16; of the RNase P motif 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; of the Group I intron by Cech et al., U.S. Pat. No. 4,987,071 and of DNAzymes 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, and Beigelman et al., International PCT publication No. WO 99/55857. 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. 2; Beigelman et al., U.S. Ser. No. 09/301,511) and Zinzyme (FIG. 3) (Beigelman et al., U.S. Ser. No. 09/301,511), all included by reference herein including drawings, can also be used in the present invention. These specific motifs or configurations 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).

[0102] In one embodiment of the present invention, a nucleic acid molecule of the instant invention can be between about 10 and 100 nucleotides in length. Exemplary enzymatic nucleic acid molecules of the invention are shown in Tables III to VII. For example, enzymatic nucleic acid molecules of the invention are preferably between about 15 and 50 nucleotides in length, more preferably between about 25 and 40 nucleotides in length, e.g., 34, 36, or 38 nucleotides in length (for example see Jarvis et al., 1996, J. Biol. Chem., 271, 29107-29112). Exemplary DNAzymes of the invention are preferably between about 15 and 40 nucleotides in length, more preferably between about 25 and 35 nucleotides in length, e.g., 29, 30, 31, or 32 nucleotides in length (see for example Santoro et al., 1998, Biochemistry, 37, 13330-13342; Chartrand et al., 1995, Nucleic Acids Research, 23, 4092-4096). Exemplary antisense molecules of the invention are preferably between about 15 and 75 nucleotides in length, more preferably between about 20 and 35 nucleotides in length, e.g., 25, 26, 27, or 28 nucleotides in length (see for example Woolf et al., 1992, PNAS, 89, 7305-7309; Milner et al., 1997, Nature Biotechnology, 15, 537-541). Exemplary triplex forming oligonucleotide molecules of the invention are preferably between about 10 and 40 nucleotides in length, more preferably between about 12 and 25 nucleotides in length, e.g., 18, 19, 20, or 21 nucleotides in length (see for example Maher et al., 1990, Biochemistry, 29, 8820-8826; Strobel and Dervan, 1990, Science, 249, 73-75). Those skilled in the art will recognize that all that is required is that the nucleic acid molecule be of sufficient length and suitable conformation for the nucleic acid molecule to interact with its target and/or catalyze a reaction contemplated herein. The length of the nucleic acid molecules of the instant invention are not limiting within the general limits stated.

[0103] Preferably, a nucleic acid molecule that modulates, for example, down-regulates IKK-gamma or PKR expression comprises between 12 and 100 bases complementary to a RNA molecule of IKK-gamma or PKR. Even more preferably, a nucleic acid molecule that modulates, for example IKK-gamma or PKR expression comprises between 14 and 24 bases complementary to a RNA molecule of IKK-gamma or PKR.

[0104] The invention provides a method for producing a class of nucleic acid-based gene modulating 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 IKK-gamma or PKR (specifically IKK-gamma or PKR genes) 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.

[0105] As used in herein "cell" is used in its usual biological sense, and does not refer to an entire multicellular organism. The cell can, for example, be in vitro, e.g., in cell culture, or present in a multicellular organism, including, e.g., birds, plants and mammals such as humans, cows, sheep, apes, monkeys, swine, dogs, and cats. The cell can be prokaryotic (e.g., bacterial cell) or eukaryotic (e.g., mammalian or plant cell).

[0106] By "IKK-gamma proteins" is meant, a peptide or protein comprising a IKK-gamma or NEMO/IKKAP1 component of the IKK complex, for example a regulatory IKK subunit involved in the assembly of the high molecular weight IKK complex and/or induction of NFKB.

[0107] By "PKR proteins" is meant, a peptide or protein comprising a protein kinase PKR activity, for example the activation of NFKB.

[0108] 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.

[0109] Nucleic acid-based inhibitors of IKK-gamma or PKR function are useful for the prevention and/or treatment of cancers and cancerous conditions such as breast, lung, prostate, colorectal, brain, esophageal, bladder, pancreatic, cervical, head and neck, and ovarian cancer, melanoma, lymphoma, glioma, multidrug resistant cancers, and any other diseases or conditions that are related to or will respond to the levels of IKK-gamma or PKR in a cell or tissue, alone or in combination with other therapies.

[0110] Nucleic acid-based inhibitors of IKK-gamma or PKR function are also useful for the prevention and/or treatment of inflammatory related diseases and conditions, including but not limited to rheumatoid arthritis, restenosis, asthma, Crohn's disease, incontinentia pigmenti, diabetes, obesity, autoimmune disease, lupus, multiple sclerosis, transplant/graft rejection, gene therapy applications, ischemia/reperfusion injury (CNS and myocardial), glomerulonephritis, sepsis, allergic airway inflammation, inflammatory bowel disease, infection, and any other inflammatory disease or condition which respond to the modulation of IKK-gamma or PKR function.

[0111] 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 or infusion pump, 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 XIII. Examples of such enzymatic nucleic acid molecules also are shown in Tables III to XIII. Examples of such enzymatic nucleic acid molecules consist essentially of sequences defined in these tables.

[0112] In 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 XIII. Such nucleic acid molecules can include sequences as shown for the binding arms of the enzymatic nucleic acid molecules in Tables III to XIII. 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 are complementary to a target sequence along a single contiguous sequence of the antisense molecule. However, in certain embodiments, an antisense molecule can bind to substrate such that the substrate molecule forms a loop, and/or an antisense molecule can bind such that the antisense molecule forms a loop. Thus, the antisense molecule can be complementary to two (or even more) non-contiguous substrate sequences or two (or even more) non-contiguous sequence portions of an antisense molecule can be complementary to a target sequence or both.

[0113] 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, VIII, and IX 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 8002), or any other Stem II region known in the art, or a nucleotide and/or non-nucleotide linker. Similarly, for other nucleic acid molecules of the instant invention, such as Inozyme, G-cleaver, amberzyme, zinzyme, DNAzyme, antisense, 2-5A antisense, triplex forming nucleic acid, and decoy nucleic acids, other sequences or non-nucleotide linkers can be present that do not interfere with the function of the nucleic acid molecule.

[0114] Sequence X can be a linker of .gtoreq.2 nucleotides in length, preferably 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 26, 30, where the nucleotides can preferably be internally base-paired to form a stem of preferably .gtoreq.2 base pairs. In yet another embodiment, the nucleotide linker X can be a nucleic acid aptamer, such as an ATP aptamer, HIV Rev aptamer (RRE), HIV Tat aptamer (TAR) and others (for a review see Gold et al., 1995, Annu. Rev. Biochem., 64, 763; and Szostak & Ellington, 1993, in The RNA World, ed. Gesteland and Atkins, pp. 511, CSH Laboratory Press). A "nucleic acid aptamer" as used herein is meant to indicate a nucleic acid sequence capable of interacting with a ligand. The ligand can be any natural or a synthetic molecule, including but not limited to a resin, metabolites, nucleosides, nucleotides, drugs, toxins, transition state analogs, peptides, lipids, proteins, amino acids, nucleic acid molecules, hormones, carbohydrates, receptors, cells, viruses, bacteria and others.

[0115] In yet another embodiment, alternatively or in addition, sequence X can be a non-nucleotide linker. Non-nucleotides as can include abasic nucleotide, polyether, polyamine, polyamide, peptide, carbohydrate, lipid, or polyhydrocarbon compounds. Specific examples include those described by Seela and Kaiser, Nucleic Acids Res. 1990, 18:6353 and Nucleic Acids Res. 1987, 15:3113; Cload and Schepartz, J. Am. Chem. Soc. 1991, 113:6324; Richardson and Schepartz, J. Am. Chem. Soc. 1991, 113:5109; Ma et al., Nucleic Acids Res. 1993, 21:2585 and Biochemistry 1993, 32:1751; Durand et al., Nucleic Acids Res. 1990, 18:6353; McCurdy et al., Nucleosides & Nucleotides 1991, 10:287; Jschke et al., Tetrahedron Lett. 1993, 34:301; Ono et al., Biochemistry 1991, 30:9914; Arnold et al., International Publication No. WO 89/02439; Usman et al., International Publication No. WO 95/06731; Dudycz et al., International Publication No. WO 95/11910 and Ferentz and Verdine, J. Am. Chem. Soc. 1991, 113:4000, all hereby incorporated by reference herein. A "non-nucleotide" further means 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 can be abasic in that it does not contain a commonly recognized nucleotide base, such as adenosine, guanine, cytosine, uracil or thymine. Thus, in a preferred embodiment, the invention features an enzymatic nucleic acid molecule having one or more non-nucleotide moieties, and having enzymatic activity to cleave an RNA or DNA molecule.

[0116] In another aspect of the invention, enzymatic nucleic acid molecules or antisense molecules that interact with target RNA molecules and down-regulate IKK-gamma or PKR (specifically IKK-gamma or PKR gene) activity are expressed from transcription units inserted into DNA or RNA vectors. The recombinant vectors are preferably DNA plasmids or viral vectors. Enzymatic nucleic acid molecule or antisense expressing viral vectors can be constructed based on, but not limited to, adeno-associated virus, retrovirus, adenovirus, or alphavirus. Preferably, the recombinant vectors capable of expressing the enzymatic nucleic acid molecules or antisense are delivered as described above, and persist in target cells. Alternatively, viral vectors can be used that provide for transient expression of enzymatic nucleic acid molecules or antisense. Such vectors can be repeatedly administered as necessary. Once expressed, the enzymatic nucleic acid molecules or antisense bind to the target RNA and down-regulate its function or expression. Delivery of enzymatic nucleic acid molecule or antisense expressing vectors can be systemic, such as by intravenous or intramuscular administration, by administration to target cells ex-planted from the patient or subject followed by reintroduction into the patient or subject, or by any other means that would allow for introduction into the desired target cell. Antisense DNA can be expressed via the use of a single stranded DNA intracellular expression vector.

[0117] By "vectors" is meant any nucleic acid- and/or viral-based technique used to deliver a desired nucleic acid.

[0118] By "subject" is meant an organism, which is a donor or recipient of explanted cells or the cells themselves. "subject" also refers to an organism to which the nucleic acid molecules of the invention can be administered. Preferably, a subject is a mammal or mammalian cells. More preferably, a subject is a human or human cells.

[0119] By "enhanced enzymatic activity" is meant to include activity measured in cells and/or in vivo where the activity is a reflection of both the catalytic activity and the stability of the nucleic acid molecules of the invention. In this invention, the product of these properties can be increased in vivo compared to an all RNA enzymatic nucleic acid or all DNA enzyme. In some cases, the activity or stability of the nucleic acid molecule can be decreased (i.e., less than ten-fold), but the overall activity of the nucleic acid molecule is enhanced, in vivo.

[0120] 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 IKK-gamma or PKR, the subject can be treated, or other appropriate cells can 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.

[0121] In a further embodiment, the described nucleic acid 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 can be used in combination with one or more known therapeutic agents to treat breast, lung, prostate, colorectal, brain, esophageal, bladder, pancreatic, cervical, head and neck, and ovarian cancer, melanoma, lymphoma, glioma, multidrug resistant cancers, rheumatoid arthritis, restenosis, asthma, Crohn's disease, diabetes, incontinentia pigmenti, obesity, autoimmune disease, lupus, multiple sclerosis, transplant/graft rejection, gene therapy applications, ischemia/reperfusion injury (CNS and myocardial), glomerulonephritis, sepsis, allergic airway inflammation, inflammatory bowel disease, infection, and any other cancerous disease or inflammatory disease or condition which respond to the modulation of IKK-gamma or PKR expression.

[0122] In another embodiment, the invention features nucleic acid-based inhibitors (e.g., enzymatic nucleic acid molecules (eg; ribozymes), antisense nucleic acids, 2-5A antisense chimeras, triplex DNA, dsRNA, antisense nucleic acids containing RNA cleaving chemical groups) and methods for their use to down regulate or inhibit the expression of genes (e.g., IKK-gamma or PKR) capable of progression and/or maintenance of cancer, inflammatory diseases, and/or other disease states which respond to the modulation of IKK-gamma or PKR expression.

[0123] 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 can or can 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 listed elements are required or mandatory, and that no other elements can be present.

[0124] Other features and advantages of the invention will be apparent from the following description of the preferred embodiments thereof, and from the claims.

Mechanism of Action of Nucleic Acid Molecules of the Invention as Proposed in the Art

[0125] Antisense: Antisense molecules can be modified or unmodified RNA, DNA, or mixed polymer oligonucleotides and primarily function by specifically binding to matching sequences resulting in inhibition of peptide synthesis (Wu-Pong, November 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).

[0126] In addition, binding of single stranded DNA to RNA can result in nuclease degradation of the heteroduplex (Wu-Pong, supra; Crooke, supra). To date, the only backbone modified DNA chemistry which 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.

[0127] 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 Sep. 21, 1998) all of these are incorporated by reference herein in their entirety.

[0128] 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 via the use of a single stranded DNA intracellular expression vector or equivalents and variations thereof.

[0129] Enzymatic Nucleic Acid: Several varieties of 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; Nakacane & 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.

[0130] Nucleic acid molecules of this invention will block to some extent IKK-gamma or PKR and/or IKK-gamma or PKR protein expression and can be used to treat disease or diagnose disease associated with the levels of IKK-gamma or PKR and/or IKK-gamma or PKR. Enzymatic nucleic acid sequences targeting IKK-gamma or PKR RNA and sequences that can be targeted with nucleic acid molecules of the invention to down-regulate IKK-gamma or PKR expression are shown in Tables III to XIII.

[0131] The enzymatic nature of an enzymatic nucleic acid molecule can allow the concentration of enzymatic nucleic acid molecule necessary to affect a therapeutic treatment to be lower. This reflects the ability of the enzymatic nucleic acid molecule to act enzymatically. Thus, a single enzymatic nucleic acid molecule is able to cleave many molecules of target RNA. In addition, the enzymatic nucleic acid molecule 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 greatly attenuate the catalytic activity of a enzymatic nucleic acid molecule.

[0132] 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).

[0133] Because of their sequence specificity, trans-cleaving enzymatic nucleic acid molecules can be used as therapeutic agents for human disease (Usman & McSwiggen, 1995 Ann. Rep. Med. Chem. 30, 285-294; Christoffersen and Marr, 1995 J. Med. Chem. 38, 2023-2037). Enzymatic nucleic acid molecules 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).

[0134] Enzymatic nucleic acid molecules of the invention that are allosterically regulated ("allozymes") can be used to modulate IKK-gamma or PKR expression. These allosteric enzymatic nucleic acids or allozymes (see for example George et al., U.S. Pat. Nos. 5,834,186 and 5,741,679, Shih et al., U.S. Pat. No. 5,589,332, Nathan et al., U.S. Pat. No. 5,871,914, Nathan and Ellington, International PCT publication No. WO 00/24931, Breaker et al., International PCT Publication Nos. WO 00/26226 and 98/27104, and Sullenger et al., International PCT publication No. WO 99/29842) are designed to respond to a signaling agent, for example, mutant IKK-gamma protein, wild-type IKK-gamma protein, mutant IKK-gamma RNA, wild-type IKK-gamma RNA, other proteins and/or RNAs involved in IKK-gamma activity, compounds, metals, polymers, molecules and/or drugs that are targeted to IKK-gamma or an IKK subunit, such as IKK-alpha or IKK-beta, expressing cells etc., which in turn modulates the activity of the enzymatic nucleic acid molecule. In response to interaction with a predetermined signaling agent, the allosteric enzymatic nucleic acid molecule's activity is activated or inhibited such that the expression of a particular target is selectively down-regulated. The target can comprise wild-type IKK-gamma, mutant IKK-gamma, a component of IKK-gamma, and/or a predetermined cellular component that modulates IKK-gamma activity. In a specific example, allosteric enzymatic nucleic acid molecules that are activated by interaction with a RNA encoding a mutant IKK-gamma protein are used as therapeutic agents in vivo. The presence of RNA encoding the mutant IKK-gamma activates the allosteric enzymatic nucleic acid molecule that subsequently cleaves the RNA encoding a mutant IKK-gamma protein resulting in the inhibition of mutant IKK-gamma protein expression. In this manner, cells that express the mutant form of the IKK-gamma protein are selectively targeted. Such an approach, can be used to treat, for example, incontinentia pigmenti.

[0135] In another non-limiting example, an allozyme can be activated by a IKK-gamma or PKR protein, peptide, or mutant polypeptide that caused the allozyme to inhibit the expression of IKK-gamma or PKR gene, by, for example, cleaving RNA encoded by IKK-gamma or PKR gene. In this non-limiting example, the allozyme acts as a decoy to inhibit the function of IKK-gamma or PKR and also inhibit the expression of IKK-gamma or PKR once activated by the IKK-gamma or PKR protein.

[0136] The nucleic acid molecules of the instant invention are also referred to as GeneBloc reagents, which are essentially nucleic acid molecules (eg; ribozymes, antisense) capable of down-regulating gene expression.

Target Sites

[0137] Targets for useful enzymatic nucleic acid molecules 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, and hereby incorporated by reference herein in 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, incorporated by reference herein. Rather than repeat the guidance provided in those documents here, below are provided specific examples of such methods, not limiting to those in the art. Enzymatic nucleic acid molecules 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 IKK-gamma or PKR 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 enzymatic nucleic acid molecule binding/cleavage sites were identified. These sites are shown in Tables III to XIII (all sequences are 5' to 3' in the tables; underlined regions can be any sequence "X" or linker X, 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 enzymatic nucleic acid molecules can be useful to test efficacy of action of the enzymatic nucleic acid molecule and/or antisense prior to testing in humans.

[0138] Antisense, hammerhead, DNAzyme, NCH, amberzyme, zinzyme or G-Cleaver enzymatic nucleic acid molecule 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.

[0139] Antisense, hammerhead, DNAzyme, NCH, amberzyme, zinzyme or G-Cleaver enzymatic nucleic acid molecule 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; and Wincott et al., 1995 Nucleic Acids Res. 23, 2677-2684; Caruthers et al., 1992, Methods in Enzymology 211,3-19.

Synthesis of Nucleic Acid Molecules

[0140] Synthesis of nucleic acids greater than 100 nucleotides in length can be difficult using automated methods, and the therapeutic cost of such molecules can be prohibitive. In this invention, small nucleic acid motifs ("small refers to nucleic acid motifs less than about 100 nucleotides in length, preferably less than about 80 nucleotides in length, and more preferably less than about 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.

[0141] Oligonucleotides (eg; 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, U.S. Pat. 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 .mu.mol 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 .mu.mol 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 .mu.L of 0.11 M=6.6 .mu.mol) of 2'-O-methyl phosphoramidite and a 105-fold excess of S-ethyl tetrazole (60 .mu.L of 0.25 M=15 .mu.mol) can be used in each coupling cycle of 2'-O-methyl residues relative to polymer-bound 5'-hydroxyl. A 22-fold excess (40 .mu.L of 0.11 M=4.4 .mu.mol) of deoxy phosphoramidite and a 70-fold excess of S-ethyl tetrazole (40 .mu.L of 0.25 M=10 .mu.mol) 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 I.sub.2, 49 mM pyridine, 9% water in THF (PERSEPTIVE.TM.). 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.

[0142] 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.degree. C. for 10 min. After cooling to -20.degree. C., the supernatant is removed from the polymer support. The support is washed three times with 1.0 mL of EtOH:MeCN:H2O/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.

[0143] The method of synthesis used for RNA and chemically modified 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; and Wincott et al., 1995, Nucleic Acids Res. 23, 2677-2684 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 .mu.mol 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 .mu.mol 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 .mu.L of 0.11 M=6.6 .mu.mol) of 2'-O-methyl phosphoramidite and a 75-fold excess of S-ethyl tetrazole (60 .mu.L of 0.25 M=15 .mu.mol) can be used in each coupling cycle of 2'-O-methyl residues relative to polymer-bound 5'-hydroxyl. A 66-fold excess (120 .mu.L of 0.11 M=13.2 .mu.mol) of alkylsilyl (ribo) protected phosphoramidite and a 150-fold excess of S-ethyl tetrazole (120 .mu.L of 0.25 M=30 .mu.mol) 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. 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); oxidation solution is 16.9 mM I.sub.2, 49 mM pyridine, 9% water in THF (PERSEPTIVE.TM.). 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.

[0144] 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.degree. C. for 10 min. After cooling to -20.degree. C., the supernatant is removed from the polymer support. The support is washed three times with 1.0 mL of EtOH:MeCN:H2O/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 .mu.l of a solution of 1.5 mL N-methylpyrrolidinone, 750 .mu.L TEA and 1 mL TEA.3HF to provide a 1.4 M HF concentration) and heated to 65.degree. C. After 1.5 h, the oligomer is quenched with 1.5 M NH.sub.4HCO.sub.3.

[0145] 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.degree. C. for 15 min. The vial is brought to r.t. TEA.3HF (0.1 mL) is added and the vial is heated at 65.degree. C. for 15 min. The sample is cooled at -20.degree. C. and then quenched with 1.5 M NH.sub.4HCO.sub.3.

[0146] For purification of the trityl-on oligomers, the quenched NH.sub.4HCO.sub.3 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.

[0147] Inactive hammerhead ribozymes or binding attenuated control (BAC) oligonucleotides can be synthesized by substituting a U for G.sub.5 and a U for A.sub.14 (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.

[0148] 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 example described above including but not limited to 96 well format, with the ratio of chemicals being used in the reaction adjusted accordingly.

[0149] 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).

[0150] 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.

[0151] The sequences of the nucleic acid molecules, including enzymatic nucleic acid molecules and antisense, that are chemically synthesized, are shown in Table XIII. The sequences of the enzymatic nucleic acid and antisense constructs that are chemically synthesized, are complementary to the Substrate sequences shown in Table XIII. 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 enzymatic nucleic acid and antisense construct sequences listed in Tables III to XIII can be formed of ribonucleotides or other nucleotides or non-nucleotides. Such enzymatic nucleic acid molecules with enzymatic activity are equivalent to the enzymatic nucleic acid molecules described specifically in the Tables.

Optimizing Activity of the Nucleic Acid Molecule of the Invention.

[0152] Chemically synthesizing nucleic acid molecules with modifications (base, sugar and/or phosphate) that prevent their degradation by serum ribonucleases can increase their potency (see e.g., Eckstein et al., International Publication No. 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; and 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 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. (All these publications are hereby incorporated by reference herein).

[0153] 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 modification 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; 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 in their totality by reference herein). 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, and are incorporated by reference herein. In view of such teachings, similar modifications can be used as described herein to modify the nucleic acid molecules of the instant invention.

[0154] While chemical modification of oligonucleotide internucleotide linkages with phosphorothioate, phosphorothioate, and/or 5'-methylphosphonate linkages improves stability, too many of these modifications can 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.

[0155] Nucleic acid molecules having chemical modifications that 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 can not be significantly lowered. Therapeutic nucleic acid molecules delivered exogenously are optimally 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. Nucleic acid molecules are preferably 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.

[0156] Use of the nucleic acid-based molecules of the invention can 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 subjects with nucleic acid molecules can also include combinations of different types of nucleic acid molecules.

[0157] Therapeutic nucleic acid molecules (e.g., enzymatic nucleic acid molecules and antisense nucleic acid molecules) delivered exogenously are optimally 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. These nucleic acid molecules should 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.

[0158] In one embodiment, nucleic acid catalysts having chemical modifications that maintain or enhance enzymatic activity are provided. Such nucleic acids are also generally more resistant to nucleases than unmodified nucleic acid. Thus, in a cell and/or in vivo the activity of the nucleic acid can not be significantly lowered. As exemplified herein such enzymatic nucleic acids are useful in a cell and/or in vivo even if activity over all is reduced about 10 fold (Burgin et al., 1996, Biochemistry, 35, 14090). Such enzymatic nucleic acids herein are said to "maintain" the enzymatic activity of an all RNA ribozyme or all DNA DNAzyme.

[0159] In another aspect the nucleic acid molecules comprise a 5' and/or a 3'-cap structure.

[0160] 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 can help in delivery and/or localization within a cell. The cap can be present at the 5'-terminus (5'-cap) or at the 3'-terminus (3'-cap) or can be present on both terminus. In non-limiting examples, the 5'-cap includes 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).

[0161] In another embodiment the 3'-cap includes, for example 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).

[0162] 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.

[0163] The term "alkyl" as used herein refers to a saturated aliphatic hydrocarbon, including straight-chain, branched-chain "isoalkyl", and cyclic alkyl groups. The term "alkyl" also comprises alkoxy, alkyl-thio, alkyl-thio-alkyl, alkoxyalkyl, alkylamino, alkenyl, alkynyl, alkoxy, cycloalkenyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, heteroaryl, C.sub.1-C.sub.6 hydrocarbyl, aryl or substituted aryl groups. Preferably, the alkyl group has 1 to 12 carbons. More preferably it is a lower alkyl of from about 1 to 7 carbons, more preferably about 1 to 4 carbons. The alkyl group can be substituted or unsubstituted. When substituted the substituted group(s) preferably comprise hydroxy, oxy, thio, amino, nitro, cyano, alkoxy, alkyl-thio, alkyl-thio-alkyl, alkoxyalkyl, alkylamino, silyl, alkenyl, alkynyl, alkoxy, cycloalkenyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, heteroaryl, C.sub.1-C.sub.6 hydrocarbyl, aryl or substituted aryl groups. The term "alkyl" also includes alkenyl groups containing at least one carbon-carbon double bond, including straight-chain, branched-chain, and cyclic groups. Preferably, the alkenyl group has about 2 to 12 carbons. More preferably it is a lower alkenyl of from about 2 to 7 carbons, more preferably about 2 to 4 carbons. The alkenyl group can be substituted or unsubstituted. When substituted the substituted group(s) preferably comprise hydroxy, oxy, thio, amino, nitro, cyano, alkoxy, alkyl-thio, alkyl-thio-alkyl, alkoxyalkyl, alkylamino, silyl, alkenyl, alkynyl, alkoxy, cycloalkenyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, heteroaryl, C.sub.1-C.sub.6 hydrocarbyl, aryl or substituted aryl groups. The term "alkyl" also includes alkynyl groups containing at least one carbon-carbon triple bond, including straight-chain, branched-chain, and cyclic groups. Preferably, the alkynyl group has about 2 to 12 carbons. More preferably it is a lower alkynyl of from about 2 to 7 carbons, more preferably about 2 to 4 carbons. The alkynyl group can be substituted or unsubstituted. When substituted the substituted group(s) preferably comprise hydroxy, oxy, thio, amino, nitro, cyano, alkoxy, alkyl-thio, alkyl-thio-alkyl, alkoxyalkyl, alkylamino, silyl, alkenyl, alkynyl, alkoxy, cycloalkenyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, heteroaryl, C.sub.1-C.sub.6 hydrocarbyl, aryl or substituted aryl groups. Alkyl groups or moieties of the invention can also include aryl, alkylaryl, carbocyclic aryl, heterocyclic aryl, amide and ester groups. 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 about 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.

[0164] The term "alkoxyalkyl" as used herein refers to an alkyl-O-alkyl ether, for example methoxyethyl or ethoxymethyl.

[0165] The term "alkyl-thio-alkyl" as used herein refers to an alkyl-S-alkyl thioether, for example methylthiomethyl or methylthioethyl.

[0166] The term "amino" as used herein refers to a nitrogen containing group as is known in the art derived from ammonia by the replacement of one or more hydrogen radicals by organic radicals. For example, the terms "aminoacyl" and "aminoalkyl" refer to specific N-substituted organic radicals with acyl and alkyl substituent groups respectively.

[0167] The term "amination" as used herein refers to a process in which an amino group or substituted amine is introduced into an organic molecule.

[0168] The term "exocyclic amine protecting moiety" as used herein refers to a nucleobase amino protecting group compatible with oligonucleotide synthesis, for example an acyl or amide group.

[0169] The term "alkenyl" as used herein refers to a straight or branched hydrocarbon of a designed number of carbon atoms containing at least one carbon-carbon double bond. Examples of "alkenyl" include vinyl, allyl, and 2-methyl-3-heptene.

[0170] The term "alkoxy" as used herein refers to an alkyl group of indicated number of carbon atoms attached to the parent molecular moiety through an oxygen bridge. Examples of alkoxy groups include, for example, methoxy, ethoxy, propoxy and isopropoxy.

[0171] The term "alkynyl" as used herein refers to a straight or branched hydrocarbon of a designed number of carbon atoms containing at least one carbon-carbon triple bond. Examples of "alkynyl" include propargyl, propyne, and 3-hexyne.

[0172] The term "aryl" as used herein refers to an aromatic hydrocarbon ring system containing at least one aromatic ring. The aromatic ring can optionally be fused or otherwise attached to other aromatic hydrocarbon rings or non-aromatic hydrocarbon rings. Examples of aryl groups include, for example, phenyl, naphthyl, 1,2,3,4-tetrahydronaphthalene and biphenyl. Preferred examples of aryl groups include phenyl and naphthyl.

[0173] The term "cycloalkenyl" as used herein refers to a C.sub.3-C.sub.8 cyclic hydrocarbon containing at least one carbon-carbon double bond. Examples of cycloalkenyl include cyclopropenyl, cyclobutenyl, cyclopentenyl, cyclopentadiene, cyclohexenyl, 1,3-cyclohexadiene, cycloheptenyl, cycloheptatrienyl, and cyclooctenyl.

[0174] The term "cycloalkyl" as used herein refers to a C.sub.3-C.sub.8 cyclic hydrocarbon. Examples of cycloalkyl include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl and cyclooctyl.

[0175] The term "cycloalkylalkyl," as used herein, refers to a C.sub.3-C.sub.7 cycloalkyl group attached to the parent molecular moiety through an alkyl group, as defined above. Examples of cycloalkylalkyl groups include cyclopropylmethyl and cyclopentylethyl.

[0176] The terms "halogen" or "halo" as used herein refers to indicate fluorine, chlorine, bromine, and iodine.

[0177] The term "heterocycloalkyl," as used herein refers to a non-aromatic ring system containing at least one heteroatom selected from nitrogen, oxygen, and sulfur. The heterocycloalkyl ring can be optionally fused to or otherwise attached to other heterocycloalkyl rings and/or non-aromatic hydrocarbon rings. Preferred heterocycloalkyl groups have from 3 to 7 members. Examples of heterocycloalkyl groups include, for example, piperazine, morpholine, piperidine, tetrahydrofuran, pyrrolidine, and pyrazole. Preferred heterocycloalkyl groups include piperidinyl, piperazinyl, morpholinyl, and pyrolidinyl.

[0178] The term "heteroaryl" as used herein refers to an aromatic ring system containing at least one heteroatom selected from nitrogen, oxygen, and sulfur. The heteroaryl ring can be fused or otherwise attached to one or more heteroaryl rings, aromatic or non-aromatic hydrocarbon rings or heterocycloalkyl rings. Examples of heteroaryl groups include, for example, pyridine, furan, thiophene, 5,6,7,8-tetrahydroisoquinoline and pyrimidine. Preferred examples of heteroaryl groups include thienyl, benzothienyl, pyridyl, quinolyl, pyrazinyl, pyrimidyl, imidazolyl, benzimidazolyl, furanyl, benzofuranyl, thiazolyl, benzothiazolyl, isoxazolyl, oxadiazolyl, isothiazolyl, benzisothiazolyl, triazolyl, tetrazolyl, pyrrolyl, indolyl, pyrazolyl, and benzopyrazolyl.

[0179] The term "C1-C6 hydrocarbyl" as used herein refers to straight, branched, or cyclic alkyl groups having 1-6 carbon atoms, optionally containing one or more carbon-carbon double or triple bonds. Examples of hydrocarbyl groups include, for example, methyl, ethyl, propyl, isopropyl, n-butyl, sec-butyl, tert-butyl, pentyl, 2-pentyl, isopentyl, neopentyl, hexyl, 2-hexyl, 3-hexyl, 3-methylpentyl, vinyl, 2-pentene, cyclopropylmethyl, cyclopropyl, cyclohexylmethyl, cyclohexyl and propargyl. When reference is made herein to C1-C6 hydrocarbyl containing one or two double or triple bonds it is understood that at least two carbons are present in the alkyl for one double or triple bond, and at least four carbons for two double or triple bonds.

[0180] By "nucleotide" is meant a heterocyclic nitrogenous base in N-glycosidic linkage with a phosphorylated sugar. Nucleotides are 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; Uhlman & Peyman, supra 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 chemically modified and other natural nucleic acid bases that can be introduced into nucleic acids include, for example, 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, quesosine, 2-thiouridine, 4-thiouridine, wybutosine, wybutoxosine, 4-acetylcytidine, 5-(carboxyhydroxymethyl)uridine, 5'-carboxymethylaminomethyl-2-thiouridine, 5-carboxymethylaminomethyluridine, beta-D-galactosylqueosine, 1-methyladenosine, 1-methylinosine, 2,2-dimethylguanosine, 3-methylcytidine, 2-methyladenosine, 2-methylguanosine, N6-methyladenosine, 7-methylguanosine, 5-methoxyaminomethyl-2-thiouridine, 5-methylaminomethyluridine, 5-methylcarbonylmethyluridine, 5-methyloxyuridine, 5-methyl-2-thiouridine, 2-methylthio-N-6-isopentenyladenosine, beta-D-mannosylqueosine, uridine-5-oxyacetic acid, 2-thiocytidine, threonine derivatives 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 can 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.

[0181] By "nucleoside" is meant a heterocyclic nitrogenous base in N-glycosidic linkage with a sugar. Nucleosides are 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 nucleoside sugar moiety. Nucleosides generally comprise a base and sugar group. The nucleosides can be unmodified or modified at the sugar, and/or base moiety, (also referred to interchangeably as nucleoside analogs, modified nucleosides, non-natural nucleosides, non-standard nucleosides 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; Uhlman & Peyman, supra 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 chemically modified and other natural nucleic acid bases that can be introduced into nucleic acids 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, quesosine, 2-thiouridine, 4-thiouridine, wybutosine, wybutoxosine, 4-acetylcytidine, 5-(carboxyhydroxymethyl)uridine, 5'-carboxymethylaminomethyl-2-thiouridine, 5-carboxymethylaminomethyluridine, beta-D-galactosylqueosine, 1-methyladenosine, 1-methylinosine, 2,2-dimethylguanosine, 3-methylcytidine, 2-methyladenosine, 2-methylguanosine, N6-methyladenosine, 7-methylguanosine, 5-methoxyaminomethyl-2-thiouridine, 5-methylaminomethyluridine, 5-methylcarbonylmethyluridine, 5-methyloxyuridine, 5-methyl-2-thiouridine, 2-methylthio-N6-isopentenyladenosine, beta-D-mannosylqueosine, uridine-5-oxyacetic acid, 2-thiocytidine, threonine derivatives and others (Burgin et al., 1996, Biochemistry, 35, 14090; Uhlman & Peyman, supra). By "modified bases" in this aspect is meant nucleoside bases other than adenine, guanine, cytosine and uracil at 1' position or their equivalents; such bases can 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.

[0182] In one embodiment, the invention features modified enzymatic nucleic acid molecules with phosphate backbone modifications comprising one or more phosphorothioate, phosphorodithioate, methylphosphonate, morpholino, amidate carbamate, carboxymethyl, acetamidate, polyamide, sulfonate, sulfonamide, sulfamate, formacetal, 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.

[0183] By "abasic" is meant sugar moieties lacking a base or having other chemical groups in place of a base at the 1' position, for example a 3',3'-linked or 5',5'-linked deoxyabasic ribose derivative (for more details see Wincott et al., International PCT publication No. WO 97/26270).

[0184] By "unmodified nucleoside" is meant one of the bases adenine, cytosine, guanine, thymine, uracil joined to the 1' carbon of .beta.-D-ribo-furanose.

[0185] 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.

[0186] In connection with 2'-modified nucleotides as described for the present invention, by "amino" is meant 2'-NH.sub.2 or 2'-O--NH.sub.2, which can 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 in their entireties.

[0187] Various modifications to nucleic acid (e.g., antisense and ribozyme) structure can be made to enhance the utility of these molecules. For example, such modifications can enhance shelf-life, half-life in vitro, stability, and ease of introduction of such oligonucleotides to the target site, including e.g., enhancing penetration of cellular membranes and conferring the ability to recognize and bind to targeted cells.

[0188] Use of these molecules can lead to better treatment of the disease progression by affording the possibility of combination therapies (e.g., multiple enzymatic nucleic acid molecules targeted to different genes, enzymatic nucleic acid molecules coupled with known small molecule inhibitors, or intermittent treatment with combinations of enzymatic nucleic acid molecules (including different enzymatic nucleic acid molecule motifs) and/or other chemical or biological molecules). The treatment of subjects with nucleic acid molecules can also include combinations of different types of nucleic acid molecules. Therapies can be devised which include a mixture of enzymatic nucleic acid molecules (including different enzymatic nucleic acid molecule motifs), antisense and/or 2-5A chimera molecules to one or more targets to alleviate symptoms of a disease.

Administration of Nucleic Acid Molecules

[0189] 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 can be utilized for the delivery of virtually any nucleic acid molecule. Nucleic acid molecules can 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. Alternatively, the nucleic acid/vehicle combination is locally delivered by direct injection or by use of an infusion pump. Other routes of delivery include, but are not limited to oral (tablet or pill form) and/or intrathecal delivery (Gold, 1997, Neuroscience, 76, 1153-1158). Other approaches include the use of various transport and carrier systems, for example, through the use of conjugates and biodegradable polymers. For a comprehensive review on drug delivery strategies including CNS delivery, see Ho et al., 1999, Curr. Opin. Mol. Ther., 1, 336-343 and Jain, Drug Delivery Systems: Technologies and Commercial Opportunities, Decision Resources, 1998 and Groothuis et al., 1997, J. NeuroVirol., 3, 387-400. 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 WO99/05094, and Klimuk et al., PCT WO99/04819 all of which have been incorporated by reference herein.

[0190] 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 subject.

[0191] The negatively charged polynucleotides of the invention can be administered (e.g., RNA, DNA or protein) and introduced into a subject 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 can also be formulated and used as tablets, capsules or elixirs for oral administration; suppositories for rectal administration; sterile solutions; suspensions for injectable administration; and the other compositions known in the art.

[0192] 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, for example, salts of hydrochloric, hydrobromic, acetic acid, and benzene sulfonic acid.

[0193] 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 subject, 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. 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.

[0194] 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 which lead to systemic absorption include, without limitations: intravenous, subcutaneous, intraperitoneal, inhalation, oral, intrapulmonary and intramuscular. Each of these administration routes expose 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 which can facilitate the association of drug with the surface of cells, such as, lymphocytes and macrophages is also useful. This approach can 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.

[0195] 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. Non-limiting examples of agents suitable for formulation with the nucleic acid molecules of the instant invention include: PEG conjugated nucleic acids, phospholipid conjugated nucleic acids, nucleic acids containing lipophilic moieties, phosphorothioates, P-glycoprotein inhibitors (such as Pluronic P85) which can enhance entry of drugs into various tissues, for example 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 implantation (Emerich, D F 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, including CNS delivery of 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. All these references are hereby incorporated herein by reference.

[0196] 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). Nucleic acid molecules of the invention can also comprise covalently attached PEG molecules of various molecular weights. 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). 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). 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. All of these references are incorporated by reference herein.

[0197] 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 can be provided. These include sodium benzoate, sorbic acid and esters of p-hydroxybenzoic acid. In addition, antioxidants and suspending agents can be used.

[0198] 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.

[0199] The nucleic acid molecules of the invention and formulations thereof can be administered orally, topically, parenterally, by inhalation or spray or rectally in dosage unit formulations containing conventional non-toxic pharmaceutically acceptable carriers, adjuvants and vehicles. The term parenteral as used herein includes percutaneous, subcutaneous, intravascular (e.g., intravenous), intramuscular, or intrathecal injection or infusion techniques and the like. In addition, there is provided a pharmaceutical formulation comprising a nucleic acid molecule of the invention and a pharmaceutically acceptable carrier. One or more nucleic acid molecules of the invention can be present in association with one or more non-toxic pharmaceutically acceptable carriers and/or diluents and/or adjuvants, and if desired other active ingredients. The pharmaceutical compositions containing nucleic acid molecules of the invention can be in a form suitable for oral use, for example, as tablets, troches, lozenges, aqueous or oily suspensions, dispersible powders or granules, emulsion, hard or soft capsules, or syrups or elixirs.

[0200] Compositions intended for oral use can be prepared according to any method known to the art for the manufacture of pharmaceutical compositions and such compositions can contain one or more such sweetening agents, flavoring agents, coloring agents or preservative agents in order to provide pharmaceutically elegant and palatable preparations. Tablets contain the active ingredient in admixture with non-toxic pharmaceutically acceptable excipients that are suitable for the manufacture of tablets. These excipients can be for example, inert diluents, such as calcium carbonate, sodium carbonate, lactose, calcium phosphate or sodium phosphate; granulating and disintegrating agents, for example, corn starch, or alginic acid; binding agents, for example starch, gelatin or acacia, and lubricating agents, for example magnesium stearate, stearic acid or talc. The tablets can be uncoated or they can be coated by known techniques. In some cases such coatings can be prepared by known techniques to delay disintegration and absorption in the gastrointestinal tract and thereby provide a sustained action over a longer period. For example, a time delay material such as glyceryl monosterate or glyceryl distearate can be employed.

[0201] Formulations for oral use can also be presented as hard gelatin capsules wherein the active ingredient is mixed with an inert solid diluent, for example, calcium carbonate, calcium phosphate or kaolin, or as soft gelatin capsules wherein the active ingredient is mixed with water or an oil medium, for example peanut oil, liquid paraffin or olive oil.

[0202] Aqueous suspensions contain the active materials in admixture with excipients suitable for the manufacture of aqueous suspensions. Such excipients are suspending agents, for example sodium carboxymethylcellulose, methylcellulose, hydropropyl-methylcellulose, sodium alginate, polyvinylpyrrolidone, gum tragacanth and gum acacia; dispersing or wetting agents can be a naturally-occurring phosphatide, for example, lecithin, or condensation products of an alkylene oxide with fatty acids, for example polyoxyethylene stearate, or condensation products of ethylene oxide with long chain aliphatic alcohols, for example heptadecaethyleneoxycetanol, or condensation products of ethylene oxide with partial esters derived from fatty acids and a hexitol such as polyoxyethylene sorbitol monooleate, or condensation products of ethylene oxide with partial esters derived from fatty acids and hexitol anhydrides, for example polyethylene sorbitan monooleate. The aqueous suspensions can also contain one or more preservatives, for example ethyl, or n-propyl p-hydroxybenzoate, one or more coloring agents, one or more flavoring agents, and one or more sweetening agents, such as sucrose or saccharin.

[0203] Oily suspensions can be formulated by suspending the active ingredients in a vegetable oil, for example arachis oil, olive oil, sesame oil or coconut oil, or in a mineral oil such as liquid paraffin. The oily suspensions can contain a thickening agent, for example beeswax, hard paraffin or cetyl alcohol. Sweetening agents and flavoring agents can be added to provide palatable oral preparations. These compositions can be preserved by the addition of an anti-oxidant such as ascorbic acid.

[0204] Dispersible powders and granules suitable for preparation of an aqueous suspension by the addition of water provide the active ingredient in admixture with a dispersing or wetting agent, suspending agent and one or more preservatives. Suitable dispersing or wetting agents or suspending agents are exemplified by those already mentioned above. Additional excipients, for example sweetening, flavoring and coloring agents, can also be present.

[0205] Pharmaceutical compositions of the invention can also be in the form of oil-in-water emulsions. The oily phase can be a vegetable oil or a mineral oil or mixtures of these. Suitable emulsifying agents can be naturally-occurring gums, for example gum acacia or gum tragacanth, naturally-occurring phosphatides, for example soy bean, lecithin, and esters or partial esters derived from fatty acids and hexitol, anhydrides, for example sorbitan monooleate, and condensation products of the said partial esters with ethylene oxide, for example polyoxyethylene sorbitan monooleate. The emulsions can also contain sweetening and flavoring agents.

[0206] Syrups and elixirs can be formulated with sweetening agents, for example glycerol, propylene glycol, sorbitol, glucose or sucrose. Such formulations can also contain a demulcent, a preservative and flavoring and coloring agents. The pharmaceutical compositions can be in the form of a sterile injectable aqueous or oleaginous suspension. This suspension can be formulated according to the known art using those suitable dispersing or wetting agents and suspending agents that have been mentioned above. The sterile injectable preparation can also be a sterile injectable solution or suspension in a non-toxic parentally acceptable diluent or solvent, for example as a solution in 1,3-butanediol. Among the acceptable vehicles and solvents that can be employed are water, Ringer's solution and isotonic sodium chloride solution. In addition, sterile, fixed oils are conventionally employed as a solvent or suspending medium. For this purpose any bland fixed oil can be employed including synthetic mono- or diglycerides. In addition, fatty acids such as oleic acid find use in the preparation of injectables.

[0207] The nucleic acid molecules of the invention can also be administered in the form of suppositories, e.g., for rectal administration of the drug. These compositions can be prepared by mixing the drug with a suitable non-irritating excipient that is solid at ordinary temperatures but liquid at the rectal temperature and will therefore melt in the rectum to release the drug. Such materials include cocoa butter and polyethylene glycols.

[0208] Nucleic acid molecules of the invention can be administered parenterally in a sterile medium. The drug, depending on the vehicle and concentration used, can either be suspended or dissolved in the vehicle. Advantageously, adjuvants such as local anesthetics, preservatives and buffering agents can be dissolved in the vehicle.

[0209] Dosage levels of the order of from about 0.1 mg to about 140 mg per kilogram of body weight per day are useful in the treatment of the above-indicated conditions (about 0.5 mg to about 7 g per patient or subject per day). The amount of active ingredient that can be combined with the carrier materials to produce a single dosage form varies depending upon the host treated and the particular mode of administration. Dosage unit forms generally contain between from about 1 mg to about 500 mg of an active ingredient.

[0210] It is understood that the specific dose level for any particular patient or subject depends upon a variety of factors including the activity of the specific compound employed, the age, body weight, general health, sex, diet, time of administration, route of administration, and rate of excretion, drug combination and the severity of the particular disease undergoing therapy.

[0211] For administration to non-human animals, the composition can also be added to the animal feed or drinking water. It can be convenient to formulate the animal feed and drinking water compositions so that the animal takes in a therapeutically appropriate quantity of the composition along with its diet. It can also be convenient to present the composition as a premix for addition to the feed or drinking water.

[0212] The nucleic acid molecules of the present invention can also be administered to a subject in combination with other therapeutic compounds to increase the overall therapeutic effect. The use of multiple compounds to treat an indication can increase the beneficial effects while reducing the presence of side effects.

[0213] 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 these references are hereby incorporated in their totalities 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 enzymatic nucleic acid (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). Gene therapy approaches specific to the CNS are described by Blesch et al., 2000, Drug News Perspect., 13, 269-280; Peterson et al., 2000, Cent. Nerv. Syst. Dis., 485-508; Peel and Klein, 2000, J. Neurosci. Methods, 98, 95-104; Hagihara et al., 2000, Gene Ther., 7, 759-763; and Herrlinger et al., 2000, Methods Mol. Med., 35, 287-312. AAV-mediated delivery of nucleic acid to cells of the nervous system is further described by Kaplitt et al., U.S. Pat. No. 6,180,613.

[0214] 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 can 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 can be used that provide for transient expression of nucleic acid molecules. Such vectors can be repeatedly administered as necessary. Once expressed, the nucleic acid molecule binds to the target mRNA. Delivery of nucleic acid molecule expressing vectors can be systemic, such as by intravenous or intra-muscular administration, by administration to target cells ex-planted from the patient or subject followed by reintroduction into the patient or subject, 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).

[0215] In one aspect the invention features an expression vector comprising a nucleic acid sequence encoding at least one of the nucleic acid molecules of the instant invention is disclosed. 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.

[0216] In another aspect the invention features an expression vector comprising: a) a transcription initiation region (e.g., eukaryotic pol I, II or III 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 can 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).

[0217] 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 III promoters are expressed at high levels in all cells; the levels of a given pol II promoter in a given cell type depends 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. 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; 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; 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).

[0218] In another aspect the invention features an expression vector comprising 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.

[0219] In another 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. 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.

[0220] 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

[0221] The following are non-limiting examples showing the selection, isolation, synthesis and activity of nucleic acids of the instant invention.

[0222] 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 IKK-gamma or PKR RNA.

Example 1

Identification of Potential Target Sites in Human IKK-Gamma and PKR RNA

[0223] The sequence of human IKK-gamma or PKR genes are screened for accessible sites using a computer-folding algorithm. Regions of the RNA that do not form secondary folding structures and contained potential enzymatic nucleic acid molecule and/or antisense binding/cleavage sites are identified. The sequences of these binding/cleavage sites are shown in Tables III-XIII.

Example 2

Selection of Enzymatic Nucleic Acid Cleavage Sites in Human IKK-Gamma and PKR RNA

[0224] Enzymatic nucleic acid molecule target sites are chosen by analyzing sequences of Human IKK-gamma (Genbank accession No: NM.sub.--003639) and PKR (Genbank accession No: NM.sub.--002759) and prioritizing the sites on the basis of folding. Enzymatic nucleic acid molecules are designed that can 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 enzymatic nucleic acid molecule sequences fold into the appropriate secondary structure. Those enzymatic nucleic acid molecules with unfavorable intramolecular interactions between the binding arms and the catalytic core were 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 3

Chemical Synthesis and Purification of Ribozymes and Antisense for Efficient Cleavage and/or Blocking of IKK-Gamma and PKR RNA

[0225] Enzymatic nucleic acid molecules and antisense constructs are designed to anneal to various sites in the RNA message. The binding arms of the enzymatic nucleic acid molecules are complementary to the target site sequences described above, while the antisense constructs are fully complementary to the target site sequences described above. The enzymatic nucleic acid molecules 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%.

[0226] Enzymatic nucleic acid molecules and antisense constructs are also synthesized from DNA templates using bacteriophage T7 RNA polymerase (Milligan and Uhlenbeck, 1989, Methods Enzymol. 180, 51). Enzymatic nucleic acid molecules 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 enzymatic nucleic acid molecules used in this study are shown below in Table XIII. The sequences of the chemically synthesized antisense constructs used in this study are complementary sequences to the Substrate sequences shown below as in Tables III to XIII.

Example 4

Enzymatic Nucleic Acid Molecule Cleavage of IKK-Gamma and PKR RNA Target In Vitro

[0227] Enzymatic nucleic acid molecules targeted to the human IKK-gamma or PKR RNA are designed and synthesized as described above. These enzymatic nucleic acid molecules can be tested for cleavage activity in vitro, for example, using the following procedure. The target sequences and the nucleotide location within the IKK-gamma or PKR RNA are given in Tables III-XIII.

[0228] Cleavage Reactions: Full-length or partially full-length, internally-labeled target RNA for enzymatic nucleic acid molecule cleavage assay is prepared by in vitro transcription in the presence of [a-.sup.32P] CTP, passed over a G 50 Sephadex column by spin chromatography and used as substrate RNA without further purification. Alternately, substrates are 5'-.sup.32P-end labeled using T4 polynucleotide kinase enzyme. Assays are performed by pre-warming a 2.times. concentration of purified enzymatic nucleic acid molecule in enzymatic nucleic acid molecule cleavage buffer (50 mM Tris-HCl, pH 7.5 at 37.degree. C., 10 mM MgCl.sub.2) and the cleavage reaction was initiated by adding the 2.times. enzymatic nucleic acid molecule mix to an equal volume of substrate RNA (maximum of 1-5 nM) that was also pre-warmed in cleavage buffer. As an initial screen, assays are carried out for 1 hour at 37.degree. C. using a final concentration of either 40 nM or 1 mM enzymatic nucleic acid molecule, i.e., enzymatic nucleic acid molecule excess. The reaction is quenched by the addition of an equal volume of 95% formamide, 20 mM EDTA, 0.05% bromophenol blue and 0.05% xylene cyanol after which the sample is heated to 95.degree. C. for 2 minutes, quick chilled and loaded onto a denaturing polyacrylamide gel. Substrate RNA and the specific RNA cleavage products generated by enzymatic nucleic acid molecule cleavage are visualized on an autoradiograph of the gel. The percentage of cleavage is determined by Phosphor Imager.RTM. quantitation of bands representing the intact substrate and the cleavage products.

Example 5

Nucleic Acid Down-Regulation of IKK-Gamma and PKR Target RNA In Vivo

[0229] Nucleic acid molecules targeted to the human IKK-gamma or PKR RNA are designed and synthesized as described above. These nucleic acid molecules can be tested for cleavage activity in vivo, for example using the procedures described below. The target sequences and the nucleotide location within the IKK-gamma or PKR RNA are given in Tables III-XIII.

Example 6

In Vivo Models Used to Evaluate the Down-Regulation of IKK-Gamma or PKR Gene Expression

[0230] A variety of endpoints have been used in cell culture models to evaluate IKK-gamma or PKR-mediated effects after treatment with anti-IKK-gamma or PKR agents. Phenotypic endpoints include inhibition of cell proliferation, apoptosis assays and reduction of IKK-gamma or PKR protein expression, or a decrease in NFKB expression. Since IKK-gamma and PKR are both involved in the induction of NFKB, NFKB can be used as a surrogate marker in cell culture, animal, and clinical studies. Because overexpression of NFKB is directly associated with increased proliferation of tumor cells, a proliferation endpoint for cell culture assays is preferably used as a primary screen. There are several methods by which this endpoint can be measured. Following treatment of cells with nucleic acid molecules, cells are allowed to grow (typically 5 days) after which either the cell viability, the incorporation of [.sup.3H] thymidine into cellular DNA and/or the cell density can be measured. The assay of cell density is very straightforward and can be performed in a 96-well format using commercially available fluorescent nucleic acid stains (such as Syto.RTM. 13 or CyQuant.RTM.). An assay using CyQuant.RTM. is described herein.

[0231] As a secondary, confirmatory endpoint a nucleic acid-mediated decrease in the level of IKK-gamma or PKR RNA and/or IKK-gamma or PKR protein expression can be evaluated. Alternately, a decrease in the level of NFKB RNA can be evaluated.

Cell Culture

[0232] Cell types that express/over-express NFKB include HeLa, macrophages, peripheral blood lymphocytes, hepatocytes, fibroblasts, endothelial cells and epithelial cells. In culture, these cells can be stimulated to express/over-express NFKB by addition of TNF-alpha PMA or IL-1-beta to the culture medium. Some of these cell types also can respond with a similar activation of NFKB following LPS treatment. Activation of NFKB in cultured cells can be evaluated by electrophoretic mobility shift assay (EMSA). Delineation of alterations in the subunits can be determined by Western blot.

Primary Screen

[0233] A useful cell culture system in evaluating NFKB modulation is human colonic epithelial cells. One suitable cell line is SW620 colon carcinoma cells (CCL227). These cells respond to stimulation with TNF-alpha, LPS and/or IL-1-beta with an increase in NFKB activation. SW620 cells are grown in MEM supplemented with 10% heat-inactivated FBS and glutamine (2 mmol/L).

[0234] TNF-alpha dose-response curves in these cells are determined by incubating cells with various concentrations of recombinant human TNF-alpha (Sigma Chemical Co.). Maximal DNA binding activity induction can occur with 150 U/ml TNF-alpha in the culture medium. Induction is typically evident within 10 minutes of treatment with TNF-alpha reaches a peak at one hour post-treatment and persists for up to 4 hours post-treatment. The primary readout can be NFKB DNA activity in nuclear extracts of SW620 cells as determined by electrophoretic mobility shift assays (EMSA). Once the appropriate TNF-alpha dose/response profile has been determined, inhibition of IKK-gamma, PKR, or NFKB activation is evaluated using specific and non-specific inhibitors of activation, sulfasalazine and steroids, respectively. Cells are incubated with inhibitors or control media for 30 minutes prior to stimulation with TNF-alpha Nuclear extracts are prepared and evaluated for DNA binding activity by EMSA. Once the activity of positive controls has been established, enzymatic nucleic acids targeting the IKK-gamma or PKR are evaluated in this system. Supershift assays using polyclonal antibodies against the NFKB or PKR protein subunits can be performed to confirm down-regulation of NFKB.

Secondary Screens

[0235] SW620 cells can be transfected with the 3.times.Ig-kappa-B-Luc reporter construct 18 hours before challenge with TNF-alpha, LPS or PMA. The readout for this assay is luciferase activity. Test compounds are applied 17.5 hours after transfection (30 minutes before challenge). Cells are harvested 24 hours after challenge and relative changes in luciferase activity is used as the endpoint. Lastly, the activation of NFKB can be visualized fluorescently. Inactive NFKB heterodimers are held in the cytoplasm by inhibitory proteins. Once activated, the free heterodimers translocate to the nucleus. Thus, the relative change in cytoplasmic versus nuclear fluorescence can indicate the degree of NFKB activation. Cells can be grown on chamber slides, treated with TNF-alpha with and without test compounds), and the location of the NFKB subunit can be determined by immunofluorescence using a FITC-labeled antibody to NFKB.

Animal Models

[0236] Evaluating the efficacy of anti-IKK-gamma or PKR agents in animal models is an important prerequisite to human clinical trials. Studies have shown that human breast carcinoma cell lines express high levels of NFKB (Sovak et al., 1997, J. Clin. Invest., 100, 2952-2960). High levels of NFKB have also been observed in carcinogen-induced primary rat mammary tumors and in human breast cancer specimins. Additionally, HER2/neu overexpression has been shown to activate NFKB (Pianetti et al., 2001, Oncogene, 20, 1287-1299). As such, xenografts of cell lines that over-express NFKB can be used in animal models of tumorigenesis and/or inflammation to study the inhibition of NFKB.

Oncology Animal Model Development

[0237] Tumor cell lines are characterized to establish their growth curves in mice. These cell lines are implanted into both nude and SCID mice and primary tumor volumes are measured 3 times per week. Growth characteristics of these tumor lines using a Matrigel implantation format can also be established. The use of other cell lines that have been engineered to express high levels of NFKB can also be used in the described studies. The tumor cell line(s) and implantation method that supports the most consistent and reliable tumor growth is used in animal studies testing the lead IKK-gamma or PKR nucleic acid(s). Nucleic acids are administered by daily subcutaneous injection or by continuous subcutaneous infusion from Alzet mini osmotic pumps beginning 3 days after tumor implantation and continuing for the duration of the study. Group sizes of at least 10 animals are employed. Efficacy is determined by statistical comparison of tumor volume of nucleic acid-treated animals to a control group of animals treated with saline alone. Because the growth of these tumors is generally slow (45-60 days), an initial endpoint is the time in days it takes to establish an easily measurable primary tumor (i.e. 50-100 mm.sup.3) in the presence or absence of nucleic acid treatment.

Inflammation Animal Model Development

[0238] Chronic, sublethal administration of indomethacin to outbred rats produces an enteropathy characterized by thickening of the small intestine and mesentery, ulcerations, granulomatous inflammation, crypt abcesses and adhesions. These lesions are similar to those that are characteristic findings in human patients with Crohn's disease (CD). Thus, any beneficial therapeutic effects revealed using this model can be extrapolated to potential benefit for patients with CD.

[0239] Male Sprague-Dawley rats (200-275 g) are utilized for these studies. Chronic intestinal inflammation is induced by two subcutaneous injections of indomethacin (7.5 mg/kg in 5% NaHCO3) administered on subsequent days (Day-0 and Day-1). Animals are followed for four days following the first indomethacin injection. The mortality rate associated with this model is typically less than 10%. On the last day of the study, animals are euthanized by CO2 asphyxiation, small intestines excised and gross pathologic findings ranked according to the following criteria: 0, normal; 1, minimal abnormalities, slight thickening of the small intestine, no adhesions; 2, obvious thickening of small intestine with 1 adhesion; 3, obvious thickening of small intestine with 2 or 3 adhesions; 4, massive adhesions to the extent that the intestine cannot be separated, contents primarily fluid; 5, severe peritonitis resulting in death. A 10-cm portion of the most affected region of the small intestine is weighed, placed in 10% neutral buffered formalin and submitted for histopathologic evaluation.

[0240] The 10 cm portion of gut from each animal is cut into five equal sections. Transverse and longitudinal sections of each portion are cut and stained with hematoxylin and eosin. All slides are read in a blinded fashion and each section is scored for necrosis (% area of involvement) and inflammatory response according to the following scale: [0241] Necrosis--1, 10%; 2, 10-25%; 3, 25-50%; 4, 50-75%; 5, 75-100%; [0242] Inflammation-- [0243] 1=minimal in mesentery and muscle or lesion [0244] 2=mild in mesentery and muscle or lesion [0245] 3=moderate in mesentery and muscle or lesion [0246] 4=marked in lesion [0247] 5=severe in lesion

[0248] The scores for each of the five sections are averaged for necrosis and for inflammation.

NFKB Levels for Patient Screening and as a Potential Endpoint

[0249] Because elevated NFKB levels can be detected in cancers, cancer patients can be pre-screened for elevated NFKB prior to admission to initial clinical trials testing an anti-IKK-gamma or PKR nucleic acid. Initial NFKB levels can be determined (by ELISA) from tumor biopsies or resected tumor samples. During clinical trials, it can be possible to monitor circulating NFKB protein by ELISA. Evaluation of serial blood/serum samples over the course of the anti-IKK-gamma or PKR nucleic acid treatment period could be useful in determining early indications of efficacy.

Example 7

Activity of Nucleic Acid Molecules Used to Down-Regulate IKK-Gamma and PKR Gene Expression

[0250] Several nucleic acid molecules targeted against IKK-gamma or PKR RNA have been designed and synthesized. These nucleic acid molecules can be tested in cell proliferation and RNA reduction assays described herein.

Proliferation Assay

[0251] The model proliferation assay used in the study requires a cell-plating density of 2,000-10,000 cells/well in 96-well plates and at least 2 cell doublings over a 5-day treatment period. Cells used in proliferation studies were either lung or ovarian cancer cells (A549 and SKOV-3 cells respectively). To calculate cell density for proliferation assays, the FIPS (fluoro-imaging processing system) method known in the art was used. This method allows for cell density measurements after nucleic acids are stained with CyQuant.RTM. dye, and has the advantage of accurately measuring cell densities over a very wide range 1,000-100,000 cells/well in 96-well format. Enzymatic nucleic acid molecules (50-200 nM) are delivered in the presence of cationic lipid at 2.5-5.0 .mu.g/mL and inhibition of proliferation was determined on day 5 post-treatment.

RNA Assay

[0252] RNA is harvested 24 hours post-treatment using the Qiagen RNeasy.RTM. 96 procedure. Real time RT-PCR (TaqMan.RTM. assay) is performed on purified RNA samples using separate primer/probe sets specific for target IKK-gamma or PKR RNA.

Indications

[0253] Particular degenerative and disease states that can be associated with IKK-gamma or PKR expression modulation include but are not limited to cancerous and/or inflammatory diseases and conditions such as breast, lung, prostate, colorectal, brain, esophageal, bladder, pancreatic, cervical, head and neck, and ovarian cancer, melanoma, lymphoma, glioma, multidrug resistant cancers, rheumatoid arthritis, restenosis, asthma, Crohn's disease, diabetes, obesity, autoimmune disease, lupus, multiple sclerosis, transplant/graft rejection, gene therapy applications, ischemia/reperfusion injury (CNS and myocardial), glomerulonephritis, sepsis, allergic airway inflammation, inflammatory bowel disease, infection, incontinentia pigmenti and any other diseases or conditions that are related to or respond to the levels of IKK-gamma or PKR in a cell or tissue. The present body of knowledge in IKK-gamma and PKR research indicates the need for methods to assay IKK-gamma and PKR activity and for compounds that can regulate IKK-gamma and PKR expression for research, diagnostic, and therapeutic use.

[0254] The use of monoclonal antibodies, chemotherapy, radiation therapy, analgesics, and/or anti-inflammatory compounds, are all non-limiting examples of a 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. Common chemotherapies that can be combined with nucleic acid molecules of the instant invention include various combinations of cytotoxic drugs to kill cancer cells. These drugs include but are not limited to paclitaxel (Taxol), docetaxel, cisplatin, methotrexate, cyclophosphamide, doxorubin, fluorouracil carboplatin, edatrexate, gemcitabine, vinorelbine etc. Those skilled in the art will recognize that other drug compounds and therapies can be similarly be readily combined with the nucleic acid molecules of the instant invention (e.g. ribozymes and antisense molecules) are hence within the scope of the instant invention.

Diagnostic Uses

[0255] The nucleic acid molecules of this invention (e.g., enzymatic nucleic acid molecules) can be used as diagnostic tools to examine genetic drift and mutations within diseased cells or to detect the presence of IKK-gamma or PKR RNA in a cell. The close relationship between enzymatic nucleic acid molecule 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 enzymatic nucleic acid molecules described in this invention, one can 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 enzymatic nucleic acid molecules can 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 can be defined as important mediators of the disease. These experiments can lead to better treatment of the disease progression by affording the possibility of combinational therapies (e.g., multiple enzymatic nucleic acid molecules targeted to different genes, enzymatic nucleic acid molecules coupled with known small molecule inhibitors, or intermittent treatment with combinations of enzymatic nucleic acid molecules and/or other chemical or biological molecules). Other in vitro uses of enzymatic nucleic acid molecules of this invention are well known in the art, and include detection of the presence of mRNAs associated with IKK-gamma or PKR-related condition. Such RNA is detected by determining the presence of a cleavage product after treatment with an enzymatic nucleic acid molecule using standard methodology.

[0256] In a specific example, enzymatic nucleic acid molecules which cleave only wild-type or mutant forms of the target RNA are used for the assay. The first enzymatic nucleic acid molecule is used to identify wild-type RNA present in the sample and the second enzymatic nucleic acid molecule is used to identify mutant RNA in the sample. As reaction controls, synthetic substrates of both wild-type and mutant RNA are cleaved by both enzymatic nucleic acid molecules to demonstrate the relative enzymatic nucleic acid molecule efficiencies in the reactions and the absence of cleavage of the "non-targeted" RNA species. The cleavage products from the synthetic substrates also serve to generate size markers for the analysis of wild-type and mutant RNAs in the sample population. Thus each analysis requires two enzymatic nucleic acid molecules, two substrates and one unknown sample which is combined into six reactions. The presence of cleavage products is 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., IKK-gamma or PKR) 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 are correlated with higher risk whether RNA levels are compared qualitatively or quantitatively. The use of enzymatic nucleic acid molecules in diagnostic applications contemplated by the instant invention is more fully described in George et al., U.S. Pat. Nos. 5,834,186 and 5,741,679, Shih et al., U.S. Pat. No. 5,589,332, Nathan et al., U.S. Pat. No. 5,871,914, Nathan and Ellington, International PCT publication No. WO 00/24931, Breaker et al., International PCT Publication Nos. WO 00/26226 and 98/27104, and Sullenger et al., International PCT publication No. WO 99/29842.

Additional Uses

[0257] Potential uses of sequence-specific enzymatic nucleic acid molecules of the instant invention can 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 can be used to establish sequence relationships between two related RNAs, and large RNAs can 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 has described 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.

[0258] 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.

[0259] 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.

[0260] It will be readily apparent to one skilled in the art that varying substitutions and modifications can 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.

[0261] The invention illustratively described herein suitably can 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" can 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 can 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.

[0262] 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.

[0263] Other embodiments are within the claims that follow. TABLE-US-00001 TABLE I Characteristics of naturally occurring ribozymes Group I Introns Size: .about.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 generate cleavage products with 3'-OH and 5'-guanosine. Additional protein cofactors required in some cases to help folding and maintenance of the active structure. Over 300 known members of this class. Found as an intervening sequence in Tetrahymena thermophila rRNA, fungal mitochondria, chloroplasts, phage T4, blue- green algae, and others. Major structural features largely established through phylogenetic comparisons, mutagenesis, and biochemical studies[.sup.i,.sup.ii]. Complete kinetic framework established for one ribozyme[.sup.iii,.sup.iv,.sup.v,.sup.vi]. Studies of ribozyme folding and substrate docking underway[.sup.vii,.sup.viii,.sup.ix]. Chemical modification investigation of important residues well established[.sup.x,.sup.xi]. The small (4-6 nt) binding site can make this ribozyme too non-specific for targeted RNA cleavage, however, the Tetrahymena group I intron has been used to repair a "defective" .beta.-galactosidase message by the ligation of new .beta.- galactosidase sequences onto the defective message[.sup.xii]. RNAse P RNA (M1 RNA) Size: .about.290 to 400 nucleotides. RNA portion of a ubiquitous ribonucleoprotein enzyme. Cleaves tRNA precursors to form mature tRNA[.sup.xiii]. Reaction mechanism: possible attack by M.sup.2+-OH to generate cleavage products with 3'-OH and 5'-phosphate. RNAse P is found throughout the prokaryotes and eukaryotes. The RNA subunit has been sequenced from bacteria, yeast, rodents, and primates. Recruitment of endogenous RNAse P for therapeutic applications is possible through hybridization of an External Guide Sequence (EGS) to the target RNA[.sup.xiv,.sup.xv] Important phosphate and 2' OH contacts recently identified[.sup.xvi,.sup.xvii] Group II Introns Size: >1000 nucleotides. Trans cleavage of target RNAs recently demonstrated[.sup.xviii,.sup.xix]. Sequence requirements not fully determined. Reaction mechanism: 2'-OH of an internal adenosine generates cleavage products 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[.sup.xx,.sup.xxi] in addition to RNA cleavage and ligation. Major structural features largely established through phylogenetic comparisons[.sup.xxii]. Important 2' OH contacts beginning to be identified[.sup.xxiii] Kinetic framework under development[.sup.xxiv] Neurospora VS RNA Size: .about.144 nucleotides. Trans cleavage of hairpin target RNAs recently demonstrated[.sup.xxv]. Sequence requirements not fully determined. Reaction mechanism: attack by 2'-OH 5' to the scissile bond to generate cleavage 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: .about.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 generate cleavage 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[.sup.xxvi,.sup.xxvii] Minimal ligation activity demonstrated (for engineering through in vitro selection)[.sup.xxviii] Complete kinetic framework established for two or more ribozymes[.sup.xxix]. Chemical modification investigation of important residues well established[.sup.xxx]. Hairpin Ribozyme Size: .about.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 variable number to the 3'-side of the cleavage site. Reaction mechanism: attack by 2'-OH 5' to the scissile bond to generate cleavage products with 2',3'-cyclic phosphate and 5'-OH ends. 3 known members of this class. Found in three plant pathogen (satellite RNAs of the tobacco ringspot virus, arabis mosaic virus and chicory yellow mottle virus) which uses RNA as the infectious agent. Essential structural features largely defined[.sup.xxxi,.sup.xxxii,.sup.xxxiii,.sup.xxxiv] Ligation activity (in addition to cleavage activity) makes ribozyme amenable to engineering through in vitro selection[.sup.xxxv] Complete kinetic framework established for one ribozyme[.sup.xxxvi]. Chemical modification investigation of important residues begun[.sup.xxxvii,.sup.xxxviii]. Hepatitis Delta Virus (HDV) Ribozyme Size: .about.60 nucleotides. Trans cleavage of target RNAs demonstrated[.sup.xxxix]. Binding sites and structural requirements not fully determined, although no sequences 5' of cleavage site are required. Folded ribozyme contains a pseudoknot structure[.sup.xl]. Reaction mechanism: attack by 2'-OH 5' to the scissile bond to generate cleavage 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[.sup.xli] .sup.iMichel, Francois; Westhof, Eric. Slippery substrates. Nat. Struct. Biol. (1994), 1(1), 5-7. .sup.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. .sup.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. .sup.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. .sup.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. .sup.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. .sup.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. .sup.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. .sup.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. .sup.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. .sup.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. .sup.xiiSullenger, Bruce A.; Cech, Thomas R.. Ribozyme-mediated repair of defective mRNA by targeted trans-splicing. Nature (London) (1994), 371(6498), 619-22. .sup.xiiiRobertson, H. D.; Altman, S.; Smith, J. D. J. Biol. Chem., 247, 5243-5251 (1972) .sup.xivForster, Anthony C.; Altman, Sidney. External guide sequences for an RNA enzyme. Science (Washington, D. C., 1883-) (1990), 249(4970), 783-6. .sup.xvYuan, Y.; Hwang, E. S.; Altman, S. Targeted cleavage of mRNA by human RNase P. Proc. Natl. Acad. Sci. USA (1992) 89, 8006-10. .sup.xviHarris, Michael E.; Pace, Norman R.. Identification of phosphates involved in catalysis by the ribozyme RNase P RNA. RNA (1995), 1(2), 210-18. .sup.xviiPan, Tao; Loria, 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. .sup.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. .sup.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. .sup.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. .sup.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. .sup.xxiiMichel, Francois; Ferat, Jean Luc. Structure and activities of group II introns. Annu. Rev. Biochem. (1995), 64, 435-61. .sup.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. .sup.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. .sup.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. .sup.xxviScott, W. G., Finch, J. T., Aaron, K. The crystal structure of an all RNA hammerhead ribozyme:Aproposed mechanism for RNA catalytic cleavage. Cell, (1995), 81, 991-1002. .sup.xxviiMcKay, Structure and function of the hammerhead ribozyme: an unfinished story. RNA, (1996), 2, 395-403. .sup.xxviiiLong, D., UhIenbeck, O., Hertel, K. Ligation with hammerhead ribozymes. U.S. Pat. No. 5,633,133. .sup.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. .sup.xxxBeigelman, L., et al., Chemical modifications of hammerhead ribozymes. J. Biol. Chem., (1995) 270, 25702-25708. .sup.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. .sup.xxxiiChowrira, Bharat M.; Berzal-Herranz, Alfredo; Burke, John M.. Novel guanosine requirement for catalysis by the hairpin ribozyme. Nature (London) (1991), 354(6351), 320-2. .sup.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. .sup.xxxivJoseph, Simpson; Berzal-Herranz, Alfredo; Chowrira, 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. .sup.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. .sup.xxxviHegg, Lisa A.; Fedor, Martha J.. Kinetics and Thermodynamics of Intermolecular Catalysis by Hairpin Ribozymes. Biochemistry (1995), 34(48), 15813-28. .sup.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.

.sup.xxxviiiSchmidt, Sabine; Beigelman, Leonid; Karpeisky, Alexander; Usman, Nassim; Sorensen, Ulrik 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. .sup.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. .sup.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. .sup.xliPuttaraju, M.; Perrotta, Anne T.; Been, Michael D.. A circular trans-acting hepatitis delta virus ribozyme. Nucleic Acids Res. (1993), 21(18), 4253-8.

[0264] TABLE-US-00002 TABLE II Reagent Equivalents Amount Wait Time* DNA Wait Time* 2'-O-methyl Wait Time*RNA A. 2.5 .mu.mol Synthesis Cycle ABI 394 Instrument Phosphoramidites 6.5 163 .mu.L 45 sec 2.5 min 7.5 min S-Ethyl Tetrazole 23.8 238 .mu.L 45 sec 2.5 min 7.5 min Acetic Anhydride 100 233 .mu.L 5 sec 5 sec 5 sec N-Methyl 186 233 .mu.L 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 .mu.L 100 sec 300 sec 300 sec Acetonitrile NA 6.67 mL NA NA NA B. 0.2 .mu.mol Synthesis Cycle ABI 394 Instrument Phosphoramidites 15 31 .mu.L 45 sec 233 sec 465 sec S-Ethyl Tetrazole 38.7 31 .mu.L 45 sec 233 min 465 sec Acetic Anhydride 655 124 .mu.L 5 sec 5 sec 5 sec N-Methyl 1245 124 .mu.L 5 sec 5 sec 5 sec Imidazole TCA 700 732 .mu.L 10 sec 10 sec 10 sec Iodine 20.6 244 .mu.L 15 sec 15 sec 15 sec Beaucage 7.7 232 .mu.L 100 sec 300 sec 300 sec Acetonitrile NA 2.64 mL NA NA NA C. 0.2 .mu.mol Synthesis Cycle 96 well Instrument Equivalents: DNA/ Amount: DNA/2'-O- Wait Time* 2'-O- Reagent 2'-O-methyl/Ribo methyl/Ribo Wait Time* DNA methyl Wait Time* Ribo Phosphoramidites 22/33/66 40/60/120 .mu.L 60 sec 180 sec 360 sec S-Ethyl Tetrazole 70/105/210 40/60/120 .mu.L 60 sec 180 min 360 sec Acetic Anhydride 265/265/265 50/50/50 .mu.L 10 sec 10 sec 10 sec N-Methyl 502/502/502 50/50/50 .mu.L 10 sec 10 sec 10 sec Imidazole TCA 238/475/475 250/500/500 .mu.L 15 sec 15 sec 15 sec Iodine 6.8/6.8/6.8 80/80/80 .mu.L 30 sec 30 sec 30 sec Beaucage 34/51/51 80/120/120 100 sec 200 sec 200 sec Acetonitrile NA 1150/1150/1150 .mu.L NA NA NA *Wait time does not include contact time during delivery.

[0265] TABLE-US-00003 TABLE III Human IKK-gamma Hammerhead and Substrate Sequence Seq Seq Pos Substrate ID Hammerhead ID 18 AUGGCCCU U GUGAUCCA 4361 UGGAUCAC CUGAUGAGGCCGUUAGGCCGAA AGGGCCAU 4555 24 CUUGUGAU C CAGGUGGG 4362 CCCACCUG CUGAUGAGGCCGUUAGGCCGAA AUCACAAG 4556 39 GGGAAACU A AGGCCCAG 4363 CUGGGCCU CUGAUGAGGCCGUUAGGCCGAA AGUUUCCC 4557 70 CGCAGACU A UCAAUCCC 4364 GGGAUUGA CUGAUGAGGCCGUUAGGCCGAA AGUCUGCG 4558 72 CAGACUAU C AAUCCCAG 4365 CUGGGAUU CUGAUGAGGCCGUUAGGCCGAA AUAGUCUG 4559 76 CUAUCAAU C CCAGUCUC 4366 GAGACUGG CUGAUGAGGCCGUUAGGCCGAA AUUGAUAG 4560 82 AUCCCAGU C UCUUCCCC 4367 GGGGAAGA CUGAUGAGGCCGUUAGGCCGAA ACUGGGAU 4561 84 CCCAGUCU C UUCCCCUC 4368 GAGGGGAA CUGAUGAGGCCGUUAGGCCGAA AGACUGGG 4562 86 CAGUCUCU U CCCCUCAC 4369 GUGAGGGG CUGAUGAGGCCGUUAGGCCGAA AGAGACUG 4563 87 AGUCUCUU C CCCUCACU 4370 AGUGAGGG CUGAUGAGGCCGUUAGGCCGAA AAGAGACU 4564 92 CUUCCCCU C ACUCCCUG 4371 CAGGGAGU CUGAUGAGGCCGUUAGGCCGAA AGGGGAAG 4565 96 CCCUCACU C CCUGUGAA 4372 UUCACAGG CUGAUGAGGCCGUUAGGCCGAA AGUGAGGG 4566 108 GUGAAGCU C UCCAGCAU 4373 AUGCUGGA CUGAUGAGGCCGUUAGGCCGAA AGCUUCAC 4567 110 GAAGCUCU C CAGCAUCA 4374 UGAUGCUG CUGAUGAGGCCGUUAGGCCGAA AGAGCUUC 4568 117 UCCAGCAU C AUCGAGGU 4375 ACCUCGAU CUGAUGAGGCCGUUAGGCCGAA AUGCUGGA 4569 120 AGCAUCAU C GAGGUCCC 4376 GGGACCUC CUGAUGAGGCCGUUAGGCCGAA AUGAUGCU 4570 126 AUCGAGGU C CCAUCAGC 4377 GCUGAUGG CUGAUGAGGCCGUUAGGCCGAA ACCUCGAU 4571 131 GGUCCCAU C AGCCCUUG 4378 CAAGGGCU CUGAUGAGGCCGUUAGGCCGAA AUGGGACC 4572 138 UCAGCCCU U GCCCUGUU 4379 AACAGGGC CUGAUGAGGCCGUUAGGCCGAA AGGGCUGA 4573 146 UGCCCUGU U GGAUGAAU 4380 AUUCAUCC CUGAUGAGGCCGUUAGGCCGAA ACAGGGCA 4574 155 GGAUGAAU A GGCACCUC 4381 GAGGUGCC CUGAUGAGGCCGUUAGGCCGAA AUUCAUCC 4575 163 AGGCACCU C UGGAAGAG 4382 CUCUUCCA CUGAUGAGGCCGUUAGGCCGAA AGCUGCCU 4576 218 CAGCAGAU C AGGACGUA 4383 UACGUCCU CUGAUGAGGCCGUUAGGCCGAA AUCUGCUG 4577 226 CAGGACGU A CUGGGCGA 4384 UCGCCCAG CUGAUGAGGCCGUUAGGCCGAA ACGUCCUG 4578 240 CGAAGAGU C UCCUCUGG 4385 CCAGAGGA CUGAUGAGGCCGUUAGGCCGAA ACUCUUCG 4579 242 AAGAGUCU C CUCUGGGG 4386 CCCCAGAG CUGAUGAGGCCGUUAGGCCGAA AGACUCUU 4580 245 AGUCUCCU C UGGGGAAG 4387 CUUCCCCA CUGAUGAGGCCGUUAGGCCGAA AGGAGACU 4581 275 ACCUGCCU U CAGAACAG 4388 CUGUUCUG CUGAUGAGGCCGUUAGGCCGAA AGGCAGGU 4582 276 CCUGCCUU C AGAACAGG 4389 CCUGUUCU CUGAUGAGGCCGUUAGGCCGAA AAGGCAGG 4583 290 AGGGCGCU C CUGAGACC 4390 GGUCUCAG CUGAUGAGGCCGUUAGGCCGAA AGCGCCCU 4584 301 GAGACCCU C CAGCGCUG 4391 CAGCGCUG CUGAUGAGGCCGUUAGGCCGAA AGGGUCUC 4585 323 AGGAGAAU C AAGAGCUC 4392 GAGCUCUU CUGAUGAGGCCGUUAGGCCGAA AUUCUCCU 4586 331 CAAGAGCU C CGAGAUGC 4393 GCAUCUCG CUGAUGAGGCCGUUAGGCCGAA AGCUCUUG 4587 343 GAUGCCAU C CGGCAGAG 4394 CUCUGCCG CUGAUGAGGCCGUUAGGCCGAA AUGGCAUC 4588 361 AACCAGAU U CUGCGGGA 4395 UCCCGCAG CUGAUGAGGCCGUUAGGCCGAA AUCUGGUU 4589 362 ACCAGAUU C UGCGGGAG 4396 CUCCCGCA CUGAUGAGGCCGUUAGGCCGAA AAUCUGGU 4590 385 GAGGAGCU U CUGCAUUU 4397 AAAUGCAG CUGAUGAGGCCGUUAGGCCGAA AGCUCCUC 4591 386 AGGAGCUU C UGCAUUUC 4398 GAAAUGCA CUGAUGAGGCCGUUAGGCCGAA AAGCUCCU 4592 392 UUCUGCAU U UCCAAGCC 4399 GGCUUGGA CUGAUGAGGCCGUUAGGCCGAA AUGCAGAA 4593 393 UCUGCAUU U CCAAGCCA 4400 UGGCUUGG CUGAUGAGGCCGUUAGGCCGAA AAUGCAGA 4594 394 CUGCAUUU C CAAGCCAG 4401 CUGGCUUG CUGAUGAGGCCGUUAGGCCGAA AAAUGCAG 4595 423 GAAGGAGU U CCUCAUGU 4402 ACAUGAGG CUGAUGAGGCCGUUAGGCCGAA ACUCCUUC 4596 424 AAGGAGUU C CUCAUGUG 4403 CACAUGAG CUGAUGAGGCCGUUAGGCCGAA AACUCCUU 4597 427 GAGUUCCU C AUGUGCAA 4404 UUGCACAU CUGAUGAGGCCGUUAGGCCGAA AGGAACUC 4598 438 GUGCAAGU U CCAGGAGG 4405 CCUCCUGG CUGAUGAGGCCGUUAGGCCGAA ACUUGCAC 4599 439 UGCAAGUU C CAGGAGGC 4406 GCCUCCUG CUGAUGAGGCCGUUAGGCCGAA AACUUGCA 4600 469 GAGAGACU C GGCCUGGA 4407 UCCAGGCC CUGAUGAGGCCGUUAGGCCGAA AGUCUCUC 4601 484 GAGAAGCU C GAUCUGAA 4408 UUCAGAUC CUGAUGAGGCCGUUAGGCCGAA AGCUUCUC 4602 488 AGCUCGAU C UGAAGAGG 4409 CCUCUUCA CUGAUGAGGCCGUUAGGCCGAA AUCGAGCU 4603 512 AGCAGGCU C UGCGGGAG 4410 CUCCCGCA CUGAUGAGGCCGUUAGGCCGAA AGCCUGCU 4604 570 CAAGGCCU C UGUGAAAG 4411 CUUUCACA CUGAUGAGGCCGUUAGGCCGAA AGGCCUUG 4605 591 GGUGACGU C CUUGCUCG 4412 CGAGCAAG CUGAUGAGGCCGUUAGGCCGAA ACGUCACC 4606 594 GACGUCCU U GCUCGGGG 4413 CCCCGAGC CUGAUGAGGCCGUUAGGCCGAA AGGACGUC 4607 598 UCCUUGCU C GGGGAGCU 4414 AGCUCCCC CUGAUGAGGCCGUUAGGCCGAA AGCAAGGA 4608 623 GCCAGAGU C GCUUGGAG 4415 CUCCAAGC CUGAUGAGGCCGUUAGGCCGAA ACUCUGGC 4609 627 GAGUCGCU U GGAGGCUG 4416 CAGCCUCC CUGAUGAGGCCGUUAGGCCGAA AGCGACUC 4610 641 CUGCCACU A AGGAAUGC 4417 GCAUUCCU CUGAUGAGGCCGUUAGGCCGAA AGUGGCAG 4611 656 GCCAGGCU C UGGAGGGU 4418 ACCCUCCA CUGAUGAGGCCGUUAGGCCGAA AGCCUGGC 4612 665 UGGAGGGU C GGGCCCGG 4419 CCGGGCCC CUGAUGAGGCCGUUAGGCCGAA ACCCUCCA 4613 787 GCCGCGCU C CGCAUGGA 4420 UCCAUGCG CUGAUGAGGCCGUUAGGCCGAA AGCGCGGC 4614 810 GGCCGCCU C GGAGGAGA 4421 UCUCCUCC CUGAUGAGGCCGUUAGGCCGAA AGGCGGCC 4615 837 GGCCCAGU U GCAGGUGG 4422 CCACCUGC CUGAUGAGGCCGUUAGGCCGAA ACUGGGCC 4616 849 GGUGGCCU A UCACCAGC 4423 GCUGGUGA CUGAUGAGGCCGUUAGGCCGAA AGGCCACC 4617 851 UGGCCUAU C ACCAGCUC 4424 GAGCUGGU CUGAUGAGGCCGUUAGGCCGAA AUAGGCCA 4618 859 CACCAGCU C UUCCAAGA 4425 UCUUGGAA CUGAUGAGGCCGUUAGGCCGAA AGCUGGUG 4619 861 CCAGCUCU U CCAAGAAU 4426 AUUCUUGG CUGAUGAGGCCGUUAGGCCGAA AGAGCUGG 4620 862 CAGCUCUU C CAAGAAUA 4427 UAUUCUUG CUGAUGAGGCCGUUAGGCCGAA AAGAGCUG 4621 870 CCAAGAAU A CGACAACC 4428 GGUUGUCG CUGAUGAGGCCGUUAGGCCGAA AUUCUUGG 4622 883 AACCACAU C AAGAGCAG 4429 CUGCUCUU CUGAUGAGGCCGUUAGGCCGAA AUGUGGUU 4623 935 UGGAAGAU C UCAAACAG 4430 CUGUUUGA CUGAUGAGGCCGUUAGGCCGAA AUCUUCCA 4624 937 GAAGAUCU C AAACAGCA 4431 UGCUGUUU CUGAUGAGGCCGUUAGGCCGAA AGAUCUUC 4625 949 CAGCAGCU C CAGCAGGC 4432 GCCUGCUG CUGAUGAGGCCGUUAGGCCGAA AGCUGCUG 4626 991 GAGGUGAU C GAUAAGCU 4433 AGCUUAUC CUGAUGAGGCCGUUAGGCCGAA AUCACCUC 4627 995 UGAUCGAU A AGCUGAAG 4434 CUUCAGCU CUGAUGAGGCCGUUAGGCCGAA AUCGAUCA 4628 1027 CACAAGAU U GUGAUGGA 4435 UCCAUCAC CUGAUGAGGCCGUUAGGCCGAA AUCUUGUG 4629 1042 GAGACCGU U CCGGUGCU 4436 AGCACCGG CUGAUGAGGCCGUUAGGCCGAA ACGGUCUC 4630 1043 AGACCGUU C CGGUGCUG 4437 CAGCACCG CUGAUGAGGCCGUUAGGCCGAA AACGGUCU 4631 1067 AGGCGGAU A UCUACAAG 4438 CUUGUAGA CUGAUGAGGCCGUUAGGCCGAA AUCCGCCU 4632 1069 GCGGAUAU C UACAAGGC 4439 GCCUUGUA CUGAUGAGGCCGUUAGGCCGAA AUAUCCGC 4633 1071 GGAUAUCU A CAAGGCGG 4440 CCGCCUUG CUGAUGAGGCCGUUAGGCCGAA AGAUAUCC 4634 1083 GGCGGACU U CCAGGCUG 4441 CAGCCUGG CUGAUGAGGCCGUUAGGCCGAA AGUCCGCC 4635 1084 GCGGACUU C CAGGCUGA 4442 UCAGCCUG CUGAUGAGGCCGUUAGGCCGAA AAGUCCGC 4636 1132 AAGGAGCU C CUGCAGGA 4443 UCCUGCAG CUGAUGAGGCCGUUAGGCCGAA AGCUCCUU 4637 1167 GAGGGAGU A CAGCAAAC 4444 GUUUGCUG CUGAUGAGGCCGUUAGGCCGAA ACUCCCUC 4638 1190 CCAGCUGU C AGGAGUCG 4445 CGACUCCU CUGAUGAGGCCGUUAGGCCGAA ACAGCUGG 4639

1197 UCAGGAGU C GGCCAGGA 4446 UCCUGGCC CUGAUGAGGCCGUUAGGCCGAA ACUCCUGA 4640 1207 GCCAGGAU C GAGGACAU 4447 AUGUCCUC CUGAUGAGGCCGUUAGGCCGAA AUCCUGGC 4641 1231 CGGCAUGU C GAGGUCUC 4448 GAGACCUC CUGAUGAGGCCGUUAGGCCGAA ACAUGCCG 4642 1237 GUCGAGGU C UCCCAGGC 4449 GCCUGGGA CUGAUGAGGCCGUUAGGCCGAA ACCUCGAC 4643 1239 CGAGGUCU C CCAGGCCC 4450 GGGCCUGG CUGAUGAGGCCGUUAGGCCGAA AGACCUCG 4644 1251 GGCCCCCU U GCCCCCCG 4451 CGGGGGGC CUGAUGAGGCCGUUAGGCCGAA AGGGGGCC 4645 1269 CCCUGCCU A CCUCUCCU 4452 AGGAGAGG CUGAUGAGGCCGUUAGGCCGAA AGGCAGGG 4646 1273 GCCUACCU C UCCUCUCC 4453 GGAGAGGA CUGAUGAGGCCGUUAGGCCGAA AGGUAGGC 4647 1275 CUACCUCU C CUCUCCCC 4454 GGGGAGAG CUGAUGAGGCCGUUAGGCCGAA AGAGGUAG 4648 1278 CCUCUCCU C UCCCCUGG 4455 CCAGGGGA CUGAUGAGGCCGUUAGGCCGAA AGGAGAGG 4649 1280 UCUCCUCU C CCCUGGCC 4456 GGCCAGGG CUGAUGAGGCCGUUAGGCCGAA AGAGGAGA 4650 1332 ACCUGACU U CUGCUGUC 4457 GACAGCAG CUGAUGAGGCCGUUAGGCCGAA AGUCAGGU 4651 1333 CCUGACUU C UGCUGUCC 4458 GGACAGCA CUGAUGAGGCCGUUAGGCCGAA AAGUCAGG 4652 1340 UCUGCUGU C CCAAGUGC 4459 GCACUUGG CUGAUGAGGCCGUUAGGCCGAA ACAGCAGA 4653 1353 GUGCCAGU A UCAGGCCC 4460 GGGCCUGA CUGAUGAGGCCGUUAGGCCGAA ACUGGCAC 4654 1355 GCCAGUAU C AGGCCCCU 4461 AGGGGCCU CUGAUGAGGCCGUUAGGCCGAA AUACUGGC 4655 1367 CCCCUGAU A UGGACACC 4462 GGUGUCCA CUGAUGAGGCCGUUAGGCCGAA AUCAGGGG 4656 1384 CUGCAGAU A CAUGUCAU 4463 AUGACAUG CUGAUGAGGCCGUUAGGCCGAA AUCUGCAG 4657 1390 AUACAUGU C AUGGAGUG 4464 CACUCCAU CUGAUGAGGCCGUUAGGCCGAA ACAUGUAU 4658 1402 GAGUGCAU U GAGUAGGG 4465 CCCUACUC CUGAUGAGGCCGUUAGGCCGAA AUGCACUC 4659 1407 CAUUGAGU A GGGCCGGC 4466 GCCGGCCC CUGAUGAGGCCGUUAGGCCGAA ACUCAAUG 4660 1464 CGUGCAGU C UGCGCUUU 4467 AAAGCGCA CUGAUGAGGCCGUUAGGCCGAA ACUGCACG 4661 1471 UCUGCGCU U UCCUCUCC 4468 GGAGAGGA CUGAUGAGGCCGUUAGGCCGAA AGCGCAGA 4662 1472 CUGCGCUU U CCUCUCCC 4469 GGGAGAGG CUGAUGAGGCCGUUAGGCCGAA AAGCGCAG 4663 1473 UGCGCUUU C CUCUCCCG 4470 CGGGAGAG CUGAUGAGGCCGUUAGGCCGAA AAAGCGCA 4664 1476 GCUUUCCU C UCCCGCCU 4471 AGGCGGGA CUGAUGAGGCCGUUAGGCCGAA AGGAAAGC 4665 1478 UUUCCUCU C CCGCCUGC 4472 GCAGGCGG CUGAUGAGGCCGUUAGGCCGAA AGAGGAAA 4666 1489 GCCUGCCU A GCCCAGGA 4473 UCCUGGGC CUGAUGAGGCCGUUAGGCCGAA AGGCAGGC 4667 1565 CGGCACCU U ACGCUUCA 4474 UGAAGCGU CUGAUGAGGCCGUUAGGCCGAA AGGUGCCG 4668 1566 GGCACCUU A CGCUUCAG 4475 CUGAAGCG CUGAUGAGGCCGUUAGGCCGAA AAGGUGCC 4669 1571 CUUACGCU U CAGCUGUU 4476 AACAGCUG CUGAUGAGGCCGUUAGGCCGAA AGCGUAAG 4670 1572 UUACGCUU C AGCUGUUG 4477 CAACAGCU CUGAUGAGGCCGUUAGGCCGAA AAGCGUAA 4671 1579 UCAGCUGU U GAUCCGCU 4478 AGCGGAUC CUGAUGAGGCCGUUAGGCCGAA ACAGCUGA 4672 1583 CUGUUGAU C CGCUGGUC 4479 GACCAGCG CUGAUGAGGCCGUUAGGCCGAA AUCAACAG 4673 1591 CCGCUGGU C CCCUCUUU 4480 AAAGAGGG CUGAUGAGGCCGUUAGGCCGAA ACCAGCGG 4674 1596 GGUCCCCU C UUUUGGGG 4481 CCCCAAAA CUGAUGAGGCCGUUAGGCCGAA AGGGGACC 4675 1598 UCCCCUCU U UUGGGGUA 4482 UACCCCAA CUGAUGAGGCCGUUAGGCCGAA AGAGGGGA 4676 1599 CCCCUCUU U UGGGGUAG 4483 CUACCCCA CUGAUGAGGCCGUUAGGCCGAA AAGAGGGG 4677 1600 CCCUCUUU U GGGGUAGA 4484 UCUACCCC CUGAUGAGGCCGUUAGGCCGAA AAAGAGGG 4678 1606 UUUGGGGU A GAUGCGGC 4485 GCCGCAUC CUGAUGAGGCCGUUAGGCCGAA ACCCCAAA 4679 1621 GCCCCGAU C AGGCCUGA 4486 UCAGGCCU CUGAUGAGGCCGUUAGGCCGAA AUCGGGGC 4680 1632 GCCUGACU C GCUGCUCU 4487 AGAGCAGC CUGAUGAGGCCGUUAGGCCGAA AGUCAGGC 4681 1639 UCGCUGCU C UUUUUGUU 4488 AACAAAAA CUGAUGAGGCCGUUAGGCCGAA AGCAGCGA 4682 1641 GCUGCUCU U UUUGUUCC 4489 GGAACAAA CUGAUGAGGCCGUUAGGCCGAA AGAGCAGC 4683 1642 CUGCUCUU U UUGUUCCC 4490 GGGAACAA CUGAUGAGGCCGUUAGGCCGAA AAGAGCAG 4684 1643 UGCUCUUU U UGUUCCCU 4491 AGGGAACA CUGAUGAGGCCGUUAGGCCGAA AAAGAGCA 4685 1644 GCUCUUUU U GUUCCCUU 4492 AAGGGAAC CUGAUGAGGCCGUUAGGCCGAA AAAAGAGC 4686 1647 CUUUUUGU U CCCUUCUG 4493 CAGAAGGG CUGAUGAGGCCGUUAGGCCGAA ACAAAAAG 4687 1648 UUUUUGUU C CCUUCUGU 4494 ACAGAAGG CUGAUGAGGCCGUUAGGCCGAA AACAAAAA 4688 1652 UGUUCCCU U CUGUCUGC 4495 GCAGACAG CUGAUGAGGCCGUUAGGCCGAA AGGGAACA 4689 1653 GUUCCCUU C UGUCUGCU 4496 AGCAGACA CUGAUGAGGCCGUUAGGCCGAA AAGGGAAC 4690 1657 CCUUCUGU C UGCUCGAA 4497 UUCGAGCA CUGAUGAGGCCGUUAGGCCGAA ACAGAAGG 4691 1662 UGUCUGCU C GAACCACU 4498 AGUGGUUC CUGAUGAGGCCGUUAGGCCGAA AGCAGACA 4692 1671 GAACCACU U GCCUCGGG 4499 CCCGAGGC CUGAUGAGGCCGUUAGGCCGAA AGUGGUUC 4693 1676 ACUUGCCU C GGGCUAAU 4500 AUUAGCCC CUGAUGAGGCCGUUAGGCCGAA AGGCAAGU 4694 1682 CUCGGGCU A AUCCCUCC 4501 GGAGGGAU CUGAUGAGGCCGUUAGGCCGAA AGCCCGAG 4695 1685 GGGCUAAU C CCUCCCUC 4502 GAGGGAGG CUGAUGAGGCCGUUAGGCCGAA AUUAGCCC 4696 1689 UAAUCCCU C CCUCUUCC 4503 GGAAGAGG CUGAUGAGGCCGUUAGGCCGAA AGGGAUUA 4697 1693 CCCUCCCU C UUCCUCCA 4504 UGGAGGAA CUGAUGAGGCCGUUAGGCCGAA AGGGAGGG 4698 1695 CUCCCUCU U CCUCCACC 4505 GGUGGAGG CUGAUGAGGCCGUUAGGCCGAA AGAGGGAG 4699 1696 UCCCUCUU C CUCCACCC 4506 GGGUGGAG CUGAUGAGGCCGUUAGGCCGAA AAGAGGGA 4700 1699 CUCUUCCU C CACCCGGC 4507 GCCGGGUG CUGAUGAGGCCGUUAGGCCGAA AGGAAGAG 4701 1719 GGGGAAGU C AAGAAUGG 4508 CCAUUCUU CUGAUGAGGCCGUUAGGCCGAA ACUUCCCC 4702 1739 CUGGGGCU C UCAGGGAG 4509 CUCCCUGA CUGAUGAGGCCGUUAGGCCGAA AGCCCCAG 4703 1741 GGGGCUCU C AGGGAGAA 4510 UUCUCCCU CUGAUGAGGCCGUUAGGCCGAA AGAGCCCC 4704 1755 GAACUGCU U CCCCUGGC 4511 GCCAGGGG CUGAUGAGGCCGUUAGGCCGAA AGCAGUUC 4705 1756 AACUGCUU C CCCUGGCA 4512 UGCCAGGG CUGAUGAGGCCGUUAGGCCGAA AAGCAGUU 4706 1781 UGGCAGCU C UUCCUCCC 4513 GGGAGGAA CUGAUGAGGCCGUUAGGCCGAA AGCUGCCA 4707 1783 GCAGCUCU U CCUCCCAC 4514 GUGGGAGG CUGAUGAGGCCGUUAGGCCGAA AGAGCUGC 4708 1784 CAGCUCUU C CUCCCACC 4515 GGUGGGAG CUGAUGAGGCCGUUAGGCCGAA AAGAGCUG 4709 1787 CUCUUCCU C CCACCGGA 4516 UCCGGUGG CUGAUGAGGCCGUUAGGCCGAA AGGAAGAG 4710 1836 GCUGCCCU C UUACCAUG 4517 CAUGGUAA CUGAUGAGGCCGUUAGGCCGAA AGGGCAGC 4711 1838 UGCCCUCU U ACCAUGCA 4518 UGCAUGGU CUGAUGAGGCCGUUAGGCCGAA AGAGGGCA 4712 1839 GCCCUCUU A CCAUGCAC 4519 GUGCAUGG CUGAUGAGGCCGUUAGGCCGAA AAGAGGGC 4713 1857 CGGGUGCU C UCCUUUUG 4520 CAAAAGGA CUGAUGAGGCCGUUAGGCCGAA AGCACCCG 4714 1859 GGUGCUCU C CUUUUGGG 4521 CCCAAAAG CUGAUGAGGCCGUUAGGCCGAA AGAGCACC 4715 1862 GCUCUCCU U UUGGGCUG 4522 CAGCCCAA CUGAUGAGGCCGUUAGGCCGAA AGGAGAGC 4716 1863 CUCUCCUU U UGGGCUGC 4523 GCAGCCCA CUGAUGAGGCCGUUAGGCCGAA AAGGAGAG 4717 1864 UCUCCUUU U GGGCUGCA 4524 UGCAGCCC CUGAUGAGGCCGUUAGGCCGAA AAAGGAGA 4718 1877 UGCAUGCU A UUCCAUUU 4525 AAAUGGAA CUGAUGAGGCCGUUAGGCCGAA AGCAUGCA 4719 1879 CAUGCUAU U CCAUUUUG 4526 CAAAAUGG CUGAUGAGGCCGUUAGGCCGAA AUAGCAUG 4720 1880 AUGCUAUU C CAUUUUGC 4527 GCAAAAUG CUGAUGAGGCCGUUAGGCCGAA AAUAGCAU 4721 1884 UAUUCCAU U UUGCAGCC 4528 GGCUGCAA CUGAUGAGGCCGUUAGGCCGAA AUGGAAUA 4722 1885 AUUCCAUU U UGCAGCCA 4529 UGGCUGCA CUGAUGAGGCCGUUAGGCCGAA AAUGGAAU

4723 1886 UUCCAUUU U GCAGCCAG 4530 CUGGCUGC CUGAUGAGGCCGUUAGGCCGAA AAAUGGAA 4724 1905 CGAUGUGU A UUUAACCA 4531 UGGUUAAA CUGAUGAGGCCGUUAGGCCGAA ACACAUCG 4725 1907 AUGUGUAU U UAACCAGU 4532 ACUGGUUA CUGAUGAGGCCGUUAGGCCGAA AUACACAU 4726 1908 UGUGUAUU U AACCAGUC 4533 GACUGGUU CUGAUGAGGCCGUUAGGCCGAA AAUACACA 4727 1909 GUGUAUUU A ACCAGUCA 4534 UGACUGGU CUGAUGAGGCCGUUAGGCCGAA AAAUACAC 4728 1916 UAACCAGU C ACUAUUGA 4535 UCAAUAGU CUGAUGAGGCCGUUAGGCCGAA ACUGGUUA 4729 1920 CAGUCACU A UUGAUGGA 4536 UCCAUCAA CUGAUGAGGCCGUUAGGCCGAA AGUGACUG 4730 1922 GUCACUAU U GAUGGACA 4537 UGUCCAUC CUGAUGAGGCCGUUAGGCCGAA AUAGUGAC 4731 1932 AUGGACAU U UGGGUUGU 4538 ACAACCCA CUGAUGAGGCCGUUAGGCCGAA AUGUCCAU 4732 1933 UGGACAUU U GGGUUGUU 4539 AACAACCC CUGAUGAGGCCGUUAGGCCGAA AAUGUCCA 4733 1938 AUUUGGGU U GUUUCCCA 4540 UGGGAAAC CUGAUGAGGCCGUUAGGCCGAA ACCCAAAU 4734 1941 UGGGUUGU U UCCCAUCU 4541 AGAUGGGA CUGAUGAGGCCGUUAGGCCGAA ACAACCCA 4735 1942 GGGUUGUU U CCCAUCUU 4542 AAGAUGGG CUGAUGAGGCCGUUAGGCCGAA AACAACCC 4736 1943 GGUUGUUU C CCAUCUUU 4543 AAAGAUGG CUGAUGAGGCCGUUAGGCCGAA AAACAACC 4737 1948 UUUCCCAU C UUUUUGUU 4544 AACAAAAA CUGAUGAGGCCGUUAGGCCGAA AUGGGAAA 4738 1950 UCCCAUCU U UUUGUUAC 4545 GUAACAAA CUGAUGAGGCCGUUAGGCCGAA AGAUGGGA 4739 1951 CCCAUCUU U UUGUUACC 4546 GGUAACAA CUGAUGAGGCCGUUAGGCCGAA AAGAUGGG 4740 1952 CCAUCUUU U UGUUACCA 4547 UGGUAACA CUGAUGAGGCCGUUAGGCCGAA AAAGAUGG 4741 1953 CAUCUUUU U GUUACCAU 4548 AUGGUAAC CUGAUGAGGCCGUUAGGCCGAA AAAAGAUG 4742 1956 CUUUUUGU U ACCAUAAA 4549 UUUAUGGU CUGAUGAGGCCGUUAGGCCGAA ACAAAAAG 4743 1957 UUUUUGUU A CCAUAAAU 4550 AUUUAUGG CUGAUGAGGCCGUUAGGCCGAA AACAAAAA 4744 1962 GUUACCAU A AAUAAUGG 4551 CCAUUAUU CUGAUGAGGCCGUUAGGCCGAA AUGGUAAC 4745 1966 CCAUAAAU A AUGGCAUA 4552 UAUGCCAU CUGAUGAGGCCGUUAGGCCGAA AUUUAUGG 4746 1974 AAUGGCAU A GUAAAAAA 4553 UUUUUUAC CUGAUGAGGCCGUUAGGCCGAA AUGCCAUU 4747 1977 GGCAUAGU A AAAAAAAA 4554 UUUUUUUU CUGAUGAGGCCGUUAGGCCGAA ACUAUGCC 4748 Input Sequence = NM_003639. Cut Site = UH/. Arm Length = 8. Core Sequence = CUGAUGAG GCCGUUAGGC CGAA NM_003639 (Homo sapiens inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase gamma (IKBKG), mRNA.; 1994 bp) Underlined region can be any X sequence or linker, as described herein.

[0266] TABLE-US-00004 TABLE IV Human IKK-gamma Inozyme and Substrate Sequence Seq Seq Pos Substrate ID Inozyme ID 10 GCACGAGC A UGGCCCUU 4749 AAGGGCCA CUGAUGAGGCCGUUAGGCCGAA ICUCGUGC 5253 15 AGCAUGGC C CUUGUGAU 4750 AUCACAAG CUGAUGAGGCCGUUAGGCCGAA ICCAUGCU 5254 16 GCAUGGCC C UUGUGAUC 4751 GAUCACAA CUGAUGAGGCCGUUAGGCCGAA IGCCAUGC 5255 17 CAUGGCCC U UGUGAUCC 4752 GGAUCACA CUGAUGAGGCCGUUAGGCCGAA IGGCCAUG 5256 25 UUGUGAUC C AGGUGGGG 4753 CCCCACCU CUGAUGAGGCCGUUAGGCCGAA IAUCACAA 5257 26 UGUGAUCC A GGUGGGGA 4754 UCCCCACC CUGAUGAGGCCGUUAGGCCGAA IGAUCACA 5258 38 GGGGAAAC U AAGGCCCA 4755 UGGGCCUU CUGAUGAGGCCGUUAGGCCGAA IUUUCCCC 5259 44 ACUAAGGC C CAGAGAAG 4756 CUUCUCUG CUGAUGAGGCCGUUAGGCCGAA ICCUUAGU 5260 45 CUAAGGCC C AGAGAAGU 4757 ACUUCUCU CUGAUGAGGCCGUUAGGCCGAA IGCCUUAG 5261 46 UAAGGCCC A GAGAAGUG 4758 CACUUCUC CUGAUGAGGCCGUUAGGCCGAA IGGCCUUA 5262 60 GUGAGGAC C CCGCAGAC 4759 GUCUGCGG CUGAUGAGGCCGUUAGGCCGAA IUCCUCAC 5263 61 UGAGGACC C CGCAGACU 4760 AGUCUGCG CUGAUGAGGCCGUUAGGCCGAA IGUCCUCA 5264 62 GAGGACCC C GCAGACUA 4761 UAGUCUGC CUGAUGAGGCCGUUAGGCCGAA IGGUCCUC 5265 65 GACCCCGC A GACUAUCA 4762 UGAUAGUC CUGAUGAGGCCGUUAGGCCGAA ICGGGGUC 5266 69 CCGCAGAC U AUCAAUCC 4763 GGAUUGAU CUGAUGAGGCCGUUAGGCCGAA IUCUGCGG 5267 73 AGACUAUC A AUCCCAGU 4764 ACUGGGAU CUGAUGAGGCCGUUAGGCCGAA IAUAGUCU 5268 77 UAUCAAUC C CAGUCUCU 4765 AGAGACUG CUGAUGAGGCCGUUAGGCCGAA IAUUGAUA 5269 78 AUCAAUCC C AGUCUCUU 4766 AAGAGACU CUGAUGAGGCCGUUAGGCCGAA IGAUUGAU 5270 79 UCAAUCCC A GUCUCUUC 4767 GAAGAGAC CUGAUGAGGCCGUUAGGCCGAA IGGAUUGA 5271 83 UCCCAGUC U CUUCCCCU 4768 AGGGGAAG CUGAUGAGGCCGUUAGGCCGAA IACUGGGA 5272 85 CCAGUCUC U UCCCCUCA 4769 UGAGGGGA CUGAUGAGGCCGUUAGGCCGAA IAGACUGG 5273 88 GUCUCUUC C CCUCACUC 4770 GAGUGAGG CUGAUGAGGCCGUUAGGCCGAA IAAGAGAC 5274 89 UCUCUUCC C CUCACUCC 4771 GGAGUGAG CUGAUGAGGCCGUUAGGCCGAA IGAAGAGA 5275 90 CUCUUCCC C UCACUCCC 4772 GGGAGUGA CUGAUGAGGCCGUUAGGCCGAA IGGAAGAG 5276 91 UCUUCCCC U CACUCCCU 4773 AGGGAGUG CUGAUGAGGCCGUUAGGCCGAA IGGGAAGA 5277 93 UUCCCCUC A CUCCCUGU 4774 ACAGGGAG CUGAUGAGGCCGUUAGGCCGAA IAGGGGAA 5278 95 CCCCUCAC U CCCUGUGA 4775 UCACAGGG CUGAUGAGGCCGUUAGGCCGAA IUGAGGGG 5279 97 CCUCACUC C CUGUGAAG 4776 CUUCACAG CUGAUGAGGCCGUUAGGCCGAA IAGUGAGG 5280 98 CUCACUCC C UGUGAAGC 4777 GCUUCACA CUGAUGAGGCCGUUAGGCCGAA IGAGUGAG 5281 99 UCACUCCC U GUGAAGCU 4778 AGCUUCAC CUGAUGAGGCCGUUAGGCCGAA IGGAGUGA 5282 107 UGUGAAGC U CUCCAGCA 4779 UGCUGGAG CUGAUGAGGCCGUUAGGCCGAA ICUUCACA 5283 109 UGAAGCUC U CCAGCAUC 4780 GAUGCUGG CUGAUGAGGCCGUUAGGCCGAA IAGCUUCA 5284 111 AAGCUCUC C AGCAUCAU 4781 AUGAUGCU CUGAUGAGGCCGUUAGGCCGAA IAGAGCUU 5285 112 AGCUCUCC A GCAUCAUC 4782 GAUGAUGC CUGAUGAGGCCGUUAGGCCGAA IGAGAGCU 5286 115 UCUCCAGC A UCAUCGAG 4783 CUCGAUGA CUGAUGAGGCCGUUAGGCCGAA ICUGGAGA 5287 118 CCAGCAUC A UCGAGGUC 4784 GACCUCGA CUGAUGAGGCCGUUAGGCCGAA IAUGCUGG 5288 127 UCGAGGUC C CAUCAGCC 4785 GGCUGAUG CUGAUGAGGCCGUUAGGCCGAA IACCUCGA 5289 128 CGAGGUCC C AUCAGCCC 4786 GGGCUGAU CUGAUGAGGCCGUUAGGCCGAA IGACCUCG 5290 129 GAGGUCCC A UCAGCCCU 4787 AGGGCUGA CUGAUGAGGCCGUUAGGCCGAA IGGACCUC 5291 132 GUCCCAUC A GCCCUUGC 4788 GCAAGGGC CUGAUGAGGCCGUUAGGCCGAA IAUGGGAC 5292 135 CCAUCAGC C CUUGCCCU 4789 AGGGCAAG CUGAUGAGGCCGUUAGGCCGAA ICUGAUGG 5293 136 CAUCAGCC C UUGCCCUG 4790 CAGGGCAA CUGAUGAGGCCGUUAGGCCGAA IGCUGAUG 5294 137 AUCAGCCC U UGCCCUGU 4791 ACAGGGCA CUGAUGAGGCCGUUAGGCCGAA IGGCUGAU 5295 141 GCCCUUGC C CUGUUGGA 4792 UCCAACAG CUGAUGAGGCCGUUAGGCCGAA ICAAGGGC 5296 142 CCCUUGCC C UGUUGGAU 4793 AUCCAACA CUGAUGAGGCCGUUAGGCCGAA IGCAAGGG 5297 143 CCUUGCCC U GUUGGAUG 4794 CAUCCAAC CUGAUGAGGCCGUUAGGCCGAA IGGCAAGG 5298 159 GAAUAGGC A CCUCUGGA 4795 UCCAGAGG CUGAUGAGGCCGUUAGGCCGAA ICCUAUUC 5299 161 AUAGGCAC C UCUGGAAG 4796 CUUCCAGA CUGAUGAGGCCGUUAGGCCGAA IUGCCUAU 5300 162 UAGGCACC U CUGGAAGA 4797 UCUUCCAG CUGAUGAGGCCGUUAGGCCGAA IGUGCCUA 5301 164 GGCACCUC U GGAAGAGC 4798 GCUCUUCC CUGAUGAGGCCGUUAGGCCGAA IAGGUGCC 5302 173 GGAAGAGC C AACUGUGU 4799 ACACAGUU CUGAUGAGGCCGUUAGGCCGAA ICUCUUCC 5303 174 GAAGAGCC A ACUGUGUG 4800 CACACAGU CUGAUGAGGCCGUUAGGCCGAA IGCUCUUC 5304 177 GAGCCAAC U GUGUGAGA 4801 UCUCACAC CUGAUGAGGCCGUUAGGCCGAA IUUGGCUC 5305 192 GAUGGUGC A GCCCAGUG 4802 CACUGGGC CUGAUGAGGCCGUUAGGCCGAA ICACCAUC 5306 195 GGUGCAGC C CAGUGGUG 4803 CACCACUG CUGAUGAGGCCGUUAGGCCGAA ICUGCACC 5307 196 GUGCAGCC C AGUGGUGG 4804 CCACCACU CUGAUGAGGCCGUUAGGCCGAA IGCUGCAC 5308 197 UGCAGCCC A GUGGUGGC 4805 GCCACCAC CUGAUGAGGCCGUUAGGCCGAA IGGCUGCA 5309 206 GUGGUGGC C CGGCAGCA 4806 UGCUGCCG CUGAUGAGGCCGUUAGGCCGAA ICCACCAC 5310 207 UGGUGGCC C GGCAGCAG 4807 CUGCUGCC CUGAUGAGGCCGUUAGGCCGAA IGCCACCA 5311 211 GGCCCGGC A GCAGAUCA 4808 UGAUCUGC CUGAUGAGGCCGUUAGGCCGAA ICCGGGCC 5312 214 CCGGCAGC A GAUCAGGA 4809 UCCUGAUC CUGAUGAGGCCGUUAGGCCGAA ICUGCCGG 5313 219 AGCAGAUC A GGACGUAC 4810 GUACGUCC CUGAUGAGGCCGUUAGGCCGAA IAUCUGCU 5314 228 GGACGUAC U GGGCGAAG 4811 CUUCGCCC CUGAUGAGGCCGUUAGGCCGAA IUACGUCC 5315 241 GAAGAGUC U CCUCUGGG 4812 CCCAGAGG CUGAUGAGGCCGUUAGGCCGAA IACUCUUC 5316 243 AGAGUCUC C UCUGGGGA 4813 UCCCCAGA CUGAUGAGGCCGUUAGGCCGAA IAGACUCU 5317 244 GAGUCUCC U CUGGGGAA 4814 UUCCCCAG CUGAUGAGGCCGUUAGGCCGAA IGAGACUC 5318 246 GUCUCCUC U GGGGAAGC 4815 GCUUCCCC CUGAUGAGGCCGUUAGGCCGAA IAGGAGAC 5319 255 GGGGAAGC C AGCCAUGC 4816 GCAUGGCU CUGAUGAGGCCGUUAGGCCGAA ICUUCCCC 5320 256 GGGAAGCC A GCCAUGCU 4817 AGCAUGGC CUGAUGAGGCCGUUAGGCCGAA IGCUUCCC 5321 259 AAGCCAGC C AUGCUGCA 4818 UGCAGCAU CUGAUGAGGCCGUUAGGCCGAA ICUGGCUU 5322 260 AGCCAGCC A UGCUGCAC 4819 GUGCAGCA CUGAUGAGGCCGUUAGGCCGAA IGCUGGCU 5323 264 AGCCAUGC U GCACCUGC 4820 GCAGGUGC CUGAUGAGGCCGUUAGGCCGAA ICAUGGCU 5324 267 CAUGCUGC A CCUGCCUU 4821 AAGGCAGG CUGAUGAGGCCGUUAGGCCGAA ICAGCAUG 5325 269 UGCUGCAC C UGCCUUCA 4822 UGAAGGCA CUGAUGAGGCCGUUAGGCCGAA IUGCAGCA 5326 270 GCUGCACC U GCCUUCAG 4823 CUGAAGGC CUGAUGAGGCCGUUAGGCCGAA IGUGCAGC 5327 273 GCACCUGC C UUCAGAAC 4824 GUUCUGAA CUGAUGAGGCCGUUAGGCCGAA ICAGGUGC 5328 274 CACCUGCC U UCAGAACA 4825 UGUUCUGA CUGAUGAGGCCGUUAGGCCGAA IGCAGGUG 5329 277 CUGCCUUC A GAACAGGG 4826 CCCUGUUC CUGAUGAGGCCGUUAGGCCGAA IAAGGCAG 5330 282 UUCAGAAC A GGGCGCUC 4827 GAGCGCCC CUGAUGAGGCCGUUAGGCCGAA IUUCUGAA 5331 289 CAGGGCGC U CCUGAGAC 4828 GUCUCAGG CUGAUGAGGCCGUUAGGCCGAA ICGCCCUG 5332 291 GGGCGCUC C UGAGACCC 4829 GGGUCUCA CUGAUGAGGCCGUUAGGCCGAA IAGCGCCC 5333 292 GGCGCUCC U GAGACCCU 4830 AGGGUCUC CUGAUGAGGCCGUUAGGCCGAA IGAGCGCC 5334 298 CCUGAGAC C CUCCAGCG 4831 CGCUGGAG CUGAUGAGGCCGUUAGGCCGAA IUCUCAGG 5335 299 CUGAGACC C UCCAGCGC 4832 GCGCUGGA CUGAUGAGGCCGUUAGGCCGAA IGUCUCAG 5336 300 UGAGACCC U CCAGCGCU 4833 AGCGCUGG CUGAUGAGGCCGUUAGGCCGAA IGGUCUCA 5337 302 AGACCCUC C AGCGCUGC 4834 GCAGCGCU CUGAUGAGGCCGUUAGGCCGAA IAGGGUCU 5338 303 GACCCUCC A GCGCUGCC 4835 GGCAGCGC CUGAUGAGGCCGUUAGGCCGAA IGAGGGUC 5339 308 UCCAGCGC U GCCUGGAG 4836 CUCCAGGC CUGAUGAGGCCGUUAGGCCGAA ICGCUGGA 5340 311 AGCGCUGC C UGGAGGAG 4837 CUCCUCCA CUGAUGAGGCCGUUAGGCCGAA ICAGCGCU 5341 312 GCGCUGCC U GGAGGAGA 4838 UCUCCUCC CUGAUGAGGCCGUUAGGCCGAA IGCAGCGC 5342 324 GGAGAAUC A AGAGCUCC 4839 GGAGCUCU CUGAUGAGGCCGUUAGGCCGAA IAUUCUCC 5343

330 UCAAGAGC U CCGAGAUG 4840 CAUCUCGG CUGAUGAGGCCGUUAGGCCGAA ICUCUUGA 5344 332 AAGAGCUC C GAGAUGCC 4841 GGCAUCUC CUGAUGAGGCCGUUAGGCCGAA IAGCUCUU 5345 340 CGAGAUGC C AUCCGGCA 4842 UGCCGGAU CUGAUGAGGCCGUUAGGCCGAA ICAUCUCG 5346 341 GAGAUGCC A UCCGGCAG 4843 CUGCCGGA CUGAUGAGGCCGUUAGGCCGAA IGCAUCUC 5347 344 AUGCCAUC C GGCAGAGC 4844 GCUCUGCC CUGAUGAGGCCGUUAGGCCGAA IAUGGCAU 5348 348 CAUCCGGC A GAGCAACC 4845 GGUUGCUC CUGAUGAGGCCGUUAGGCCGAA ICCGGAUG 5349 353 GGCAGAGC A ACCAGAUU 4846 AAUCUGGU CUGAUGAGGCCGUUAGGCCGAA ICUCUGCC 5350 356 AGAGCAAC C AGAUUCUG 4847 CAGAAUCU CUGAUGAGGCCGUUAGGCCGAA IUUGCUCU 5351 357 GAGCAACC A GAUUCUGC 4848 GCAGAAUC CUGAUGAGGCCGUUAGGCCGAA IGUUGCUC 5352 363 CCAGAUUC U GCGGGAGC 4849 GCUCCCGC CUGAUGAGGCCGUUAGGCCGAA IAAUCUGG 5353 374 GGGAGCGC U GCGAGGAG 4850 CUCCUCGC CUGAUGAGGCCGUUAGGCCGAA ICGCUCCC 5354 384 CGAGGAGC U UCUGCAUU 4851 AAUGCAGA CUGAUGAGGCCGUUAGGCCGAA ICUCCUCG 5355 387 GGAGCUUC U GCAUUUCC 4852 GGAAAUGC CUGAUGAGGCCGUUAGGCCGAA IAAGCUCC 5356 390 GCUUCUGC A UUUCCAAG 4853 CUUGGAAA CUGAUGAGGCCGUUAGGCCGAA ICAGAAGC 5357 395 UGCAUUUC C AAGCCAGC 4854 GCUGGCUU CUGAUGAGGCCGUUAGGCCGAA IAAAUGCA 5358 396 GCAUUUCC A AGCCAGCC 4855 GGCUGGCU CUGAUGAGGCCGUUAGGCCGAA IGAAAUGC 5359 400 UUCCAAGC C AGCCAGAG 4856 CUCUGGCU CUGAUGAGGCCGUUAGGCCGAA ICUUGGAA 5360 401 UCCAAGCC A GCCAGAGG 4857 CCUCUGGC CUGAUGAGGCCGUUAGGCCGAA IGCUUGGA 5361 404 AAGCCAGC C AGAGGGAG 4858 CUCCCUCU CUGAUGAGGCCGUUAGGCCGAA ICUGGCUU 5362 405 AGCCAGCC A GAGGGAGG 4859 CCUCCCUC CUGAUGAGGCCGUUAGGCCGAA IGCUGGCU 5363 425 AGGAGUUC C UCAUGUGC 4860 UCACAUGA CUGAUGAGGCCGUUAGGCCGAA IAACUCCU 5364 426 GGAGUUCC U CAUGUGCA 4861 UGCACAUG CUGAUGAGGCCGUUAGGCCGAA IGAACUCC 5365 428 AGUUCCUC A UGUGCAAG 4862 CUUGCACA CUGAUGAGGCCGUUAGGCCGAA IAGGAACU 5366 434 UCAUGUGC A AGUUCCAG 4863 CUGGAACU CUGAUGAGGCCGUUAGGCCGAA ICACAUGA 5367 440 GCAAGUUC C AGGAGGCC 4864 GGCCUCCU CUGAUGAGGCCGUUAGGCCGAA IAACUUGC 5368 441 CAAGUUCC A GGAGGCCA 4865 UGGCCUCC CUGAUGAGGCCGUUAGGCCGAA IGAACUUG 5369 448 CAGGAGGC C AGGAAACU 4866 AGUUUCCU CUGAUGAGGCCGUUAGGCCGAA ICCUCCUG 5370 449 AGGAGGCC A GGAAACUG 4867 CAGUUUCC CUGAUGAGGCCGUUAGGCCGAA IGCCUCCU 5371 456 CAGGAAAC U GGUGGAGA 4868 UCUCCACC CUGAUGAGGCCGUUAGGCCGAA IUUUCCUG 5372 468 GGAGAGAC U CGGCCUGG 4869 CCAGGCCG CUGAUGAGGCCGUUAGGCCGAA IUCUCUCC 5373 473 GACUCGGC C UGGAGAAG 4870 CUUCUCCA CUGAUGAGGCCGUUAGGCCGAA ICCGAGUC 5374 474 ACUCGGCC U GGAGAAGC 4871 GCUUCUCC CUGAUGAGGCCGUUAGGCCGAA IGCCGAGU 5375 483 GGAGAAGC U CGAUCUGA 4872 UCAGAUCG CUGAUGAGGCCGUUAGGCCGAA ICUUCUCC 5376 489 GCUCGAUC U GAAGAGGC 4873 GCCUCUUC CUGAUGAGGCCGUUAGGCCGAA IAUCGAGC 5377 498 GAAGAGGC A GAAGGAGC 4874 GCUCCUUC CUGAUGAGGCCGUUAGGCCGAA ICCUCUUC 5378 507 GAAGGAGC A GGCUCUGC 4875 GCAGAGCC CUGAUGAGGCCGUUAGGCCGAA ICUCCUUC 5379 511 GAGCAGGC U CUGCGGGA 4876 UCCCGCAG CUGAUGAGGCCGUUAGGCCGAA ICCUGCUC 5380 513 GCAGGCUC U GCGGGAGG 4877 CCUCCCGC CUGAUGAGGCCGUUAGGCCGAA IAGCCUGC 5381 528 GGUGGAGC A CCUGAAGA 4878 UCUUCAGG CUGAUGAGGCCGUUAGGCCGAA ICUCCACC 5382 530 UGGAGCAC C UGAAGAGA 4879 UCUCUUCA CUGAUGAGGCCGUUAGGCCGAA IUGCUCCA 5383 531 GGAGCACC U GAAGAGAU 4880 AUCUCUUC CUGAUGAGGCCGUUAGGCCGAA IGUGCUCC 5384 542 AGAGAUGC C AGCAGCAG 4881 CUGCUGCU CUGAUGAGGCCGUUAGGCCGAA ICAUCUCU 5385 543 GAGAUGCC A GCAGCAGA 4882 UCUGCUGC CUGAUGAGGCCGUUAGGCCGAA IGCAUCUC 5386 546 AUGCCAGC A GCAGAUGG 4883 CCAUCUGC CUGAUGAGGCCGUUAGGCCGAA ICUGGCAU 5387 549 CCAGCAGC A GAUGGCUG 4884 CAGCCAUC CUGAUGAGGCCGUUAGGCCGAA ICUGCUGG 5388 556 CAGAUGGC U GAGGACAA 4885 UUGUCCUC CUGAUGAGGCCGUUAGGCCGAA ICCAUCUG 5389 563 CUGAGGAC A AGGCCUCU 4886 AGAGGCCU CUGAUGAGGCCGUUAGGCCGAA IUCCUCAG 5390 568 GACAAGGC C UCUGUGAA 4887 UUCACAGA CUGAUGAGGCCGUUAGGCCGAA ICCUUGUC 5391 569 ACAAGGCC U CUGUGAAA 4888 UUUCACAG CUGAUGAGGCCGUUAGGCCGAA IGCCUUGU 5392 571 AAGGCCUC U GUGAAAGC 4889 GCUUUCAC CUGAUGAGGCCGUUAGGCCGAA IAGGCCUU 5393 580 GUGAAAGC C CAGGUGAC 4890 GUCACCUG CUGAUGAGGCCGUUAGGCCGAA ICUUUCAC 5394 581 UGAAAGCC C AGGUGACG 4891 CGUCACCU CUGAUGAGGCCGUUAGGCCGAA IGCUUUCA 5395 582 GAAAGCCC A GGUGACGU 4892 ACGUCACC CUGAUGAGGCCGUUAGGCCGAA IGGCUUUC 5396 592 GUGACGUC C UUGCUCGG 4893 CCGAGCAA CUGAUGAGGCCGUUAGGCCGAA IACGUCAC 5397 593 UGACGUCC U UGCUCGGG 4894 CCCGAGCA CUGAUGAGGCCGUUAGGCCGAA IGACGUCA 5398 597 GUCCUUGC U CGGGGAGC 4895 GCUCCCCG CUGAUGAGGCCGUUAGGCCGAA ICAAGGAC 5399 606 CGGGGAGC U GCAGGAGA 4896 UCUCCUGC CUGAUGAGGCCGUUAGGCCGAA ICUCCCCG 5400 609 GGAGCUGC A GGAGAGCC 4897 GGCUCUCC CUGAUGAGGCCGUUAGGCCGAA ICAGCUCC 5401 617 AGGAGAGC C AGAGUCGC 4898 GCGACUCU CUGAUGAGGCCGUUAGGCCGAA ICUCUCCU 5402 618 GGAGAGCC A GAGUCGCU 4899 AGCGACUC CUGAUGAGGCCGUUAGGCCGAA IGCUCUCC 5403 626 AGAGUCGC U UGGAGGCU 4900 AGCCUCCA CUGAUGAGGCCGUUAGGCCGAA ICGACUCU 5404 634 UUGGAGGC U GCCACUAA 4901 UUAGUGGC CUGAUGAGGCCGUUAGGCCGAA ICCUCCAA 5405 637 GAGGCUGC C ACUAAGGA 4902 UCCUUAGU CUGAUGAGGCCGUUAGGCCGAA ICAGCCUC 5406 638 AGGCUGCC A CUAAGGAA 4903 UUCCUUAG CUGAUGAGGCCGUUAGGCCGAA IGCAGCCU 5407 640 GCUGCCAC U AAGGAAUG 4904 CAUUCCUU CUGAUGAGGCCGUUAGGCCGAA IUGGCAGC 5408 650 AGGAAUGC C AGGCUCUG 4905 CAGAGCCU CUGAUGAGGCCGUUAGGCCGAA ICAUUCCU 5409 651 GGAAUGCC A GGCUCUGG 4906 CCAGAGCC CUGAUGAGGCCGUUAGGCCGAA IGCAUUCC 5410 655 UGCCAGGC U CUGGAGGG 4907 CCCUCCAG CUGAUGAGGCCGUUAGGCCGAA ICCUGGCA 5411 657 CCAGGCUC U GGAGGGUC 4908 GACCCUCC CUGAUGAGGCCGUUAGGCCGAA IAGCCUGG 5412 670 GGUCGGGC C CGGGCGGC 4909 GCCGCCCG CUGAUGAGGCCGUUAGGCCGAA ICCCGACC 5413 671 GUCGGGCC C GGGCGGCC 4910 GGCCGCCC CUGAUGAGGCCGUUAGGCCGAA IGCCCGAC 5414 679 CGGGCGGC C AGCGAGCA 4911 UGCUCGCU CUGAUGAGGCCGUUAGGCCGAA ICCGCCCG 5415 680 GGGCGGCC A GCGAGCAG 4912 CUGCUCGC CUGAUGAGGCCGUUAGGCCGAA IGCCGCCC 5416 687 CAGCGAGC A GGCGCGGC 4913 GCCGCGCC CUGAUGAGGCCGUUAGGCCGAA ICUCGCUG 5417 696 GGCGCGGC A GCUGGAGA 4914 UCUCCAGC CUGAUGAGGCCGUUAGGCCGAA ICCGCGCC 5418 699 GCGGCAGC U GGAGAGUG 4915 CACUCUCC CUGAUGAGGCCGUUAGGCCGAA ICUGCCGC 5419 720 CGAGGCGC U GCAGCAGC 4916 GCUGCUGC CUGAUGAGGCCGUUAGGCCGAA ICGCCUCG 5420 723 GGCGCUGC A GCAGCAGC 4917 GCUGCUGC CUGAUGAGGCCGUUAGGCCGAA ICAGCGCC 5421 726 GCUGCAGC A GCAGCACA 4918 UGUGCUGC CUGAUGAGGCCGUUAGGCCGAA ICUGCAGC 5422 729 GCAGCAGC A GCACAGCG 4919 CGCUGUGC CUGAUGAGGCCGUUAGGCCGAA ICUGCUGC 5423 732 GCAGCAGC A CAGCGUGC 4920 GCACGCUG CUGAUGAGGCCGUUAGGCCGAA ICUGCUGC 5424 734 AGCAGCAC A GCGUGCAG 4921 CUGCACGC CUGAUGAGGCCGUUAGGCCGAA IUGCUGCU 5425 741 CAGCGUGC A GGUGGACC 4922 GGUCCACC CUGAUGAGGCCGUUAGGCCGAA ICACGCUG 5426 749 AGGUGGAC C AGCUGCGC 4923 GCGCAGCU CUGAUGAGGCCGUUAGGCCGAA IUCCACCU 5427

750 GGUGGACC A GCUGCGCA 4924 UGCGCAGC CUGAUGAGGCCGUUAGGCCGAA IGUCCACC 5428 753 GGACCAGC U GCGCAUGC 4925 GCAUGCGC CUGAUGAGGCCGUUAGGCCGAA ICUGGUCC 5429 758 AGCUGCGC A UGCAGGGC 4926 GCCCUGCA CUGAUGAGGCCGUUAGGCCGAA ICGCAGCU 5430 762 GCGCAUGC A GGGCCAGA 4927 UCUGGCCC CUGAUGAGGCCGUUAGGCCGAA ICAUGCGC 5431 767 UGCAGGGC C AGAGCGUG 4928 CACGCUCU CUGAUGAGGCCGUUAGGCCGAA ICCCUGCA 5432 768 GCAGGGCC A GAGCGUGG 4929 CCACGCUC CUGAUGAGGCCGUUAGGCCGAA IGCCCUGC 5433 781 GUGGAGGC C GCGCUCCG 4930 CGGAGCGC CUGAUGAGGCCGUUAGGCCGAA ICCUCCAC 5434 786 GGCCGCGC U CCGCAUGG 4931 CCAUGCGG CUGAUGAGGCCGUUAGGCCGAA ICGCGGCC 5435 788 CCGCGCUC C GCAUGGAG 4932 CUCCAUGC CUGAUGAGGCCGUUAGGCCGAA IAGCGCGG 5436 791 CGCUCCGC A UGGAGCGC 4933 GCGCUCCA CUGAUGAGGCCGUUAGGCCGAA ICGGAGCG 5437 800 UGGAGCGC C AGGCCGCC 4934 GGCGGCCU CUGAUGAGGCCGUUAGGCCGAA ICGCUCCA 5438 801 GGAGCGCC A GGCCGCCU 4935 AGGCGGCC CUGAUGAGGCCGUUAGGCCGAA IGCGCUCC 5439 805 CGCCAGGC C GCCUCGGA 4936 UCCGAGGC CUGAUGAGGCCGUUAGGCCGAA ICCUGGCG 5440 808 CAGGCCGC C UCGGAGGA 4937 UCCUCCGA CUGAUGAGGCCGUUAGGCCGAA ICGGCCUG 5441 809 AGGCCGCC U CGGAGGAG 4938 CUCCUCCG CUGAUGAGGCCGUUAGGCCGAA IGCGGCCU 5442 828 GAGGAAGC U GGCCCAGU 4939 ACUGGGCC CUGAUGAGGCCGUUAGGCCGAA ICUUCCUC 5443 832 AAGCUGGC C CAGUUGCA 4940 UGCAACUG CUGAUGAGGCCGUUAGGCCGAA ICCAGCUU 5444 833 AGCUGGCC C AGUUGCAG 4941 CUGCAACU CUGAUGAGGCCGUUAGGCCGAA IGCCAGCU 5445 834 GCUGGCCC A GUUGCAGG 4942 CCUGCAAC CUGAUGAGGCCGUUAGGCCGAA IGGCCAGC 5446 840 CCAGUUGC A GGUGGCCU 4943 AGGCCACC CUGAUGAGGCCGUUAGGCCGAA ICAACUGG 5447 847 CAGGUGGC C UAUCACCA 4944 UGGUGAUA CUGAUGAGGCCGUUAGGCCGAA ICCACCUG 5448 848 AGGUGGCC U AUCACCAG 4945 CUGGUGAU CUGAUGAGGCCGUUAGGCCGAA IGCCACCU 5449 852 GGCCUAUC A CCAGCUCU 4946 AGAGCUGG CUGAUGAGGCCGUUAGGCCGAA IAUAGGCC 5450 854 CCUAUCAC C AGCUCUUC 4947 GAAGAGCU CUGAUGAGGCCGUUAGGCCGAA IUGAUAGG 5451 855 CUAUCACC A GCUCUUCC 4948 GGAAGAGC CUGAUGAGGCCGUUAGGCCGAA IGUGAUAG 5452 858 UCACCAGC U CUUCCAAG 4949 CUUGGAAG CUGAUGAGGCCGUUAGGCCGAA ICUGGUGA 5453 860 ACCAGCUC U UCCAAGAA 4950 UUCUUGGA CUGAUGAGGCCGUUAGGCCGAA IAGCUGGU 5454 863 AGCUCUUC C AAGAAUAC 4951 GUAUUCUU CUGAUGAGGCCGUUAGGCCGAA IAAGAGCU 5455 864 GCUCUUCC A AGAAUACG 4952 CGUAUUCU CUGAUGAGGCCGUUAGGCCGAA IGAAGAGC 5456 875 AAUACGAC A ACCACAUC 4953 GAUGUGGU CUGAUGAGGCCGUUAGGCCGAA IUCGUAUU 5457 878 ACGACAAC C ACAUCAAG 4954 CUUGAUGU CUGAUGAGGCCGUUAGGCCGAA IUUGUCGU 5458 879 CGACAACC A CAUCAAGA 4955 UCUUGAUG CUGAUGAGGCCGUUAGGCCGAA IGUUGUCG 5459 881 ACAACCAC A UCAAGAGC 4956 GCUCUUGA CUGAUGAGGCCGUUAGGCCGAA IUGGUUGU 5460 884 ACCACAUC A AGAGCAGC 4957 GCUGCUCU CUGAUGAGGCCGUUAGGCCGAA IAUGUGGU 5461 890 UCAAGAGC A GCGUGGUG 4958 CACCACGC CUGAUGAGGCCGUUAGGCCGAA ICUCUUGA 5462 902 UGGUGGGC A GUGAGCGG 4959 CCGCUCAC CUGAUGAGGCCGUUAGGCCGAA ICCCACCA 5463 924 AGGAAUGC A GCUGGAAG 4960 CUUCCAGC CUGAUGAGGCCGUUAGGCCGAA ICAUUCCU 5464 927 AAUGCAGC U GGAAGAUC 4961 GAUCUUCC CUGAUGAGGCCGUUAGGCCGAA ICUGCAUU 5465 936 GGAAGAUC U CAAACAGC 4962 GCUGUUUG CUGAUGAGGCCGUUAGGCCGAA IAUCUUCC 5466 938 AAGAUCUC A AACAGCAG 4963 CUGCUGUU CUGAUGAGGCCGUUAGGCCGAA IAGAUCUU 5467 942 UCUCAAAC A GCAGCUCC 4964 GGAGCUGC CUGAUGAGGCCGUUAGGCCGAA IUUUGAGA 5468 945 CAAACAGC A GCUCCAGC 4965 GCUGGAGC CUGAUGAGGCCGUUAGGCCGAA ICUGUUUG 5469 948 ACAGCAGC U CCAGCAGG 4966 CCUGCUGG CUGAUGAGGCCGUUAGGCCGAA ICUGCUGU 5470 950 AGCAGCUC C AGCAGGCC 4967 GGCCUGCU CUGAUGAGGCCGUUAGGCCGAA IAGCUGCU 5471 951 GCAGCUCC A GCAGGCCG 4968 CGGCCUGC CUGAUGAGGCCGUUAGGCCGAA IGAGCUGC 5472 954 GCUCCAGC A GGCCGAGG 4969 CCUCGGCC CUGAUGAGGCCGUUAGGCCGAA ICUGGAGC 5473 958 CAGCAGGC C GAGGAGGC 4970 GCCUCCUC CUGAUGAGGCCGUUAGGCCGAA ICCUGCUG 5474 967 GAGGAGGC C CUGGUGGC 4971 GCCACCAG CUGAUGAGGCCGUUAGGCCGAA ICCUCCUC 5475 968 AGGAGGCC C UGGUGGCC 4972 GGCCACCA CUGAUGAGGCCGUUAGGCCGAA IGCCUCCU 5476 969 GGAGGCCC U GGUGGCCA 4973 UGGCCACC CUGAUGAGGCCGUUAGGCCGAA IGGCCUCC 5477 976 CUGGUGGC C AAACAGGA 4974 UCCUGUUU CUGAUGAGGCCGUUAGGCCGAA ICCACCAG 5478 977 UGGUGGCC A AACAGGAG 4975 CUCCUGUU CUGAUGAGGCCGUUAGGCCGAA IGCCACCA 5479 981 GGCCAAAC A GGAGGUGA 4976 UCACCUCC CUGAUGAGGCCGUUAGGCCGAA IUUUGGCC 5480 999 CGAUAAGC U GAAGGAGG 4977 CCUCCUUC CUGAUGAGGCCGUUAGGCCGAA ICUUAUCG 5481 1012 GAGGAGGC C GAGCAGCA 4978 UGCUGCUC CUGAUGAGGCCGUUAGGCCGAA ICCUCCUC 5482 1017 GGCCGAGC A GCACAAGA 4979 UCUUGUGC CUGAUGAGGCCGUUAGGCCGAA ICUCGGCC 5483 1020 CGAGCAGC A CAAGAUUG 4980 CAAUCUUG CUGAUGAGGCCGUUAGGCCGAA ICUGCUCG 5484 1022 AGCAGCAC A AGAUUGUG 4981 CACAAUCU CUGAUGAGGCCGUUAGGCCGAA IUGCUGCU 5485 1039 AUGGAGAC C GUUCCGGU 4982 ACCGGAAC CUGAUGAGGCCGUUAGGCCGAA IUCUCCAU 5486 1044 GACCGUUC C GGUGCUGA 4983 UCAGCACC CUGAUGAGGCCGUUAGGCCGAA IAACGGUC 5487 1050 UCCGGUGC U GAAGGCCC 4984 GGGCCUUC CUGAUGAGGCCGUUAGGCCGAA ICACCGGA 5488 1057 CUGAAGGC C CAGGCGGA 4985 UCCGCCUG CUGAUGAGGCCGUUAGGCCGAA ICCUUCAG 5489 1058 UGAAGGCC C AGGCGGAU 4986 AUCCGCCU CUGAUGAGGCCGUUAGGCCGAA IGCCUUCA 5490 1059 GAAGGCCC A GGCGGAUA 4987 UAUCCGCC CUGAUGAGGCCGUUAGGCCGAA IGGCCUUC 5491 1070 CGGAUAUC U ACAAGGCG 4988 CGCCUUGU CUGAUGAGGCCGUUAGGCCGAA IAUAUCCG 5492 1073 AUAUCUAC A AGGCGGAC 4989 GUCCGCCU CUGAUGAGGCCGUUAGGCCGAA IUAGAUAU 5493 1082 AGGCGGAC U UCCAGGCU 4990 AGCCUGGA CUGAUGAGGCCGUUAGGCCGAA IUCCGCCU 5494 1085 CGGACUUC C AGGCUGAG 4991 CUCAGCCU CUGAUGAGGCCGUUAGGCCGAA IAAGUCCG 5495 1086 GGACUUCC A GGCUGAGA 4992 UCUCAGCC CUGAUGAGGCCGUUAGGCCGAA IGAAGUCC 5496 1090 UUCCAGGC U GAGAGGCA 4993 UGCCUCUC CUGAUGAGGCCGUUAGGCCGAA ICCUGGAA 5497 1098 UGAGAGGC A GGCCCGGG 4994 CCCGGGCC CUGAUGAGGCCGUUAGGCCGAA ICCUCUCA 5498 1102 AGGCAGGC C CGGGAGAA 4995 UUCUCCCG CUGAUGAGGCCGUUAGGCCGAA ICCUGCCU 5499 1103 GGCAGGCC C GGGAGAAG 4996 CUUCUCCC CUGAUGAGGCCGUUAGGCCGAA IGCCUGCC 5500 1113 GGAGAAGC U GGCCGAGA 4997 UCUCGGCC CUGAUGAGGCCGUUAGGCCGAA ICUUCUCC 5501 1117 AAGCUGGC C GAGAAGAA 4998 UUCUUCUC CUGAUGAGGCCGUUAGGCCGAA ICCAGCUU 5502 1131 GAAGGAGC U CCUGCAGG 4999 CCUGCAGG CUGAUGAGGCCGUUAGGCCGAA ICUCCUUC 5503 1133 AGGAGCUC C UGCAGGAG 5000 CUCCUGCA CUGAUGAGGCCGUUAGGCCGAA IAGCUCCU 5504 1134 GGAGCUCC U GCAGGAGC 5001 GCUCCUGC CUGAUGAGGCCGUUAGGCCGAA IGAGCUCC 5505 1137 GCUCCUGC A GGAGCAGC 5002 GCUGCUCC CUGAUGAGGCCGUUAGGCCGAA ICAGGAGC 5506 1143 GCAGGAGC A GCUGGAGC 5003 GCUCCAGC CUGAUGAGGCCGUUAGGCCGAA ICUCCUGC 5507 1146 GGAGCAGC U GGAGCAGC 5004 GCUGCUCC CUGAUGAGGCCGUUAGGCCGAA ICUGCUCC 5508 1152 GCUGGAGC A GCUGCAGA 5005 UCUGCAGC CUGAUGAGGCCGUUAGGCCGAA ICUCCAGC 5509 1155 GGAGCAGC U GCAGAGGG 5006 CCCUCUGC CUGAUGAGGCCGUUAGGCCGAA ICUGCUCC 5510

1158 GCAGCUGC A GAGGGAGU 5007 ACUCCCUC CUGAUGAGGCCGUUAGGCCGAA ICAGCUGC 5511 1169 GGGAGUAC A GCAAACUG 5008 CAGUUUGC CUGAUGAGGCCGUUAGGCCGAA IUACUCCC 5512 1172 AGUACAGC A AACUGAAG 5009 CUUCAGUU CUGAUGAGGCCGUUAGGCCGAA ICUGUACU 5513 1176 CAGCAAAC U GAAGGCCA 5010 UGGCCUUC CUGAUGAGGCCGUUAGGCCGAA IUUUGCUG 5514 1183 CUGAAGGC C AGCUGUCA 5011 UGACAGCU CUGAUGAGGCCGUUAGGCCGAA ICCUUCAG 5515 1184 UGAAGGCC A GCUGUCAG 5012 CUGACAGC CUGAUGAGGCCGUUAGGCCGAA IGCCUUCA 5516 1187 AGGCCAGC U GUCAGGAG 5013 CUCCUGAC CUGAUGAGGCCGUUAGGCCGAA ICUGGCCU 5517 1191 CAGCUGUC A GGAGUCGG 5014 CCGACUCC CUGAUGAGGCCGUUAGGCCGAA TACACCUG 5518 1201 GAGUCGGC C AGGAUCGA 5015 UCGAUCCU CUGAUGAGGCCGUUAGGCCGAA ICCGACUC 5519 1202 AGUCGGCC A GGAUCGAG 5016 CUCGAUCC CUGAUGAGGCCGUUAGGCCGAA IGCCGACU 5520 1214 UCGAGGAC A UGAGGAAG 5017 CUUCCUCA CUGAUGAGGCCGUUAGGCCGAA IUCCUCGA 5521 1227 GAAGCGGC A UGUCGAGG 5018 CCUCGACA CUGAUGAGGCCGUUAGGCCGAA ICCGCUUC 5522 1238 UCGAGGUC U CCCAGGCC 5019 GGCCUGGG CUGAUGAGGCCGUUAGGCCGAA IACCUCGA 5523 1240 GAGGUCUC C CAGGCCCC 5020 GGGGCCUG CUGAUGAGGCCGUUAGGCCGAA IAGACCUC 5524 1241 AGGUCUCC C AGGCCCCC 5021 GGGGGCCU CUGAUGAGGCCGUUAGGCCGAA IGAGACCU 5525 1242 GGUCUCCC A GGCCCCCU 5022 AGGGGGCC CUGAUGAGGCCGUUAGGCCGAA IGGAGACC 5526 1246 UCCCAGGC C CCCUUGCC 5023 GGCAAGGG CUGAUGAGGCCGUUAGGCCGAA ICCUGGGA 5527 1247 CCCAGGCC C CCUUGCCC 5024 GGGCAAGG CUGAUGAGGCCGUUAGGCCGAA IGCCUGGG 5528 1248 CCAGGCCC C CUUGCCCC 5025 GGGGCAAG CUGAUGAGGCCGUUAGGCCGAA IGGCCUGG 5529 1249 CAGGCCCC C UUGCCCCC 5026 GGGGGCAA CUGAUGAGGCCGUUAGGCCGAA IGGGCCUG 5530 1250 AGGCCCCC U UGCCCCCC 5027 GGGGGGCA CUGAUGAGGCCGUUAGGCCGAA IGGGGCCU 5531 1254 CCCCUUGC C CCCCGCCC 5028 GGGCGGGG CUGAUGAGGCCGUUAGGCCGAA ICAAGGGG 5532 1255 CCCUUGCC C CCCGCCCC 5029 GGGGCGGG CUGAUGAGGCCGUUAGGCCGAA IGCAAGGG 5533 1256 CCUUGCCC C CCGCCCCU 5030 AGGGGCGG CUGAUGAGGCCGUUAGGCCGAA IGGCAAGG 5534 1257 CUUGCCCC C CGCCCCUG 5031 CAGGGGCG CUGAUGAGGCCGUUAGGCCGAA IGGGCAAG 5535 1258 UUGCCCCC C GCCCCUGC 5032 GCAGGGGC CUGAUGAGGCCGUUAGGCCGAA IGGGGCAA 5536 1261 CCCCCCGC C CCUGCCUA 5033 UAGGCAGG CUGAUGAGGCCGUUAGGCCGAA ICGGGGGG 5537 1262 CCCCCGCC C CUGCCUAC 5034 GUAGGCAG CUGAUGAGGCCGUUAGGCCGAA IGCGGGGG 5538 1263 CCCCGCCC C UGCCUACC 5035 GGUAGGCA CUGAUGAGGCCGUUAGGCCGAA IGGCGGGG 5539 1264 CCCGCCCC U GCCUACCU 5036 AGGUAGGC CUGAUGAGGCCGUUAGGCCGAA IGGGCGGG 5540 1267 GCCCCUGC C UACCUCUC 5037 GAGAGGUA CUGAUGAGGCCGUUAGGCCGAA ICAGGGGC 5541 1268 CCCCUGCC U ACCUCUCC 5038 GGAGAGGU CUGAUGAGGCCGUUAGGCCGAA IGCAGGGG 5542 1271 CUGCCUAC C UCUCCUCU 5039 AGAGGAGA CUGAUGAGGCCGUUAGGCCGAA IUAGGCAG 5543 1272 UGCCUACC U CUCCUCUC 5040 GAGAGGAG CUGAUGAGGCCGUUAGGCCGAA IGUAGGCA 5544 1274 CCUACCUC U CCUCUCCC 5041 GGGAGAGG CUGAUGAGGCCGUUAGGCCGAA IAGGUAGG 5545 1276 UACCUCUC C UCUCCCCU 5042 AGGGGAGA CUGAUGAGGCCGUUAGGCCGAA IAGAGGUA 5546 1277 ACCUCUCC U CUCCCCUG 5043 CAGGGGAG CUGAUGAGGCCGUUAGGCCGAA IGAGAGGU 5547 1279 CUCUCCUC U CCCCUGGC 5044 GCCAGGGG CUGAUGAGGCCGUUAGGCCGAA IAGGAGAG 5548 1281 CUCCUCUC C CCUGGCCC 5045 GGGCCAGG CUGAUGAGGCCGUUAGGCCGAA IAGAGGAG 5549 1282 UCCUCUCC C CUGGCCCU 5046 AGGGCCAG CUGAUGAGGCCGUUAGGCCGAA IGAGAGGA 5550 1283 CCUCUCCC C UGGCCCUG 5047 CAGGGCCA CUGAUGAGGCCGUUAGGCCGAA IGGAGAGG 5551 1284 CUCUCCCC U GGCCCUGC 5048 GCAGGGCC CUGAUGAGGCCGUUAGGCCGAA IGGGAGAG 5552 1288 CCCCUGGC C CUGCCCAG 5049 CUGGGCAG CUGAUGAGGCCGUUAGGCCGAA ICCAGGGG 5553 1289 CCCUGGCC C UGCCCAGC 5050 GCUGGGCA CUGAUGAGGCCGUUAGGCCGAA IGCCAGGG 5554 1290 CCUGGCCC U GCCCAGCC 5051 GGCUGGGC CUGAUGAGGCCGUUAGGCCGAA IGGCCAGG 5555 1293 GGCCCUGC C CAGCCAGA 5052 UCUGGCUG CUGAUGAGGCCGUUAGGCCGAA ICAGGGCC 5556 1294 GCCCUGCC C AGCCAGAG 5053 CUCUGGCU CUGAUGAGGCCGUUAGGCCGAA IGCAGGGC 5557 1295 CCCUGCCC A GCCAGAGG 5054 CCUCUGGC CUGAUGAGGCCGUUAGGCCGAA IGGCAGGG 5558 1298 UGCCCAGC C AGAGGAGG 5055 CCUCCUCU CUGAUGAGGCCGUUAGGCCGAA ICUGGGCA 5559 1299 GCCCAGCC A GAGGAGGA 5056 UCCUCCUC CUGAUGAGGCCGUUAGGCCGAA IGCUGGGC 5560 1310 GGAGGAGC C CCCCCGAG 5057 CUCGGGGG CUGAUGAGGCCGUUAGGCCGAA ICUCCUCC 5561 1311 GAGGAGCC C CCCCGAGG 5058 CCUCGGGG CUGAUGAGGCCGUUAGGCCGAA IGGUCCUC 5562 1312 AGGAGCCC C CCCGAGGA 5059 UCCUCGGG CUGAUGAGGCCGUUAGGCCGAA IGGCUCCU 5563 1313 GGAGCCCC C CCGAGGAG 5060 CUCCUCGG CUGAUGAGGCCGUUAGGCCGAA IGGGCUCC 5564 1314 GAGCCCCC C CGAGGAGC 5061 GCUCCUCG CUGAUGAGGCCGUUAGGCCGAA IGGGGCUC 5565 1315 AGCCCCCC C GAGGAGCC 5062 GGCUCCUC CUGAUGAGGCCGUUAGGCCGAA IGGGGGCU 5566 1323 CGAGGAGC C ACCUGACU 5063 AGUCAGGU CUGAUGAGGCCGUUAGGCCGAA ICUCCUCG 5567 1324 GAGGAGCC A CCUGACUU 5064 AAGUCAGG CUGAUGAGGCCGUUAGGCCGAA IGCUCCUC 5568 1326 GGAGCCAC C UGACUUCU 5065 AGAAGUCA CUGAUGAGGCCGUUAGGCCGAA IUGGCUCC 5569 1327 GAGCCACC U GACUUCUG 5066 CAGAAGUC CUGAUGAGGCCGUUAGGCCGAA IGUGGCUC 5570 1331 CACCUGAC U UCUGCUGU 5067 ACAGCAGA CUGAUGAGGCCGUUAGGCCGAA IUCAGGUG 5571 1334 CUGACUUC U GCUGUCCC 5068 GGGACAGC CUGAUGAGGCCGUUAGGCCGAA IAAGUCAG 5572 1337 ACUUCUGC U GUCCCAAG 5069 CUUGGGAC CUGAUGAGGCCGUUAGGCCGAA ICAGAAGU 5573 1341 CUGCUGUC C CAAGUGCC 5070 GGCACUUG CUGAUGAGGCCGUUAGGCCGAA IACAGCAG 5574 1342 UGCUGUCC C AAGUGCCA 5071 UGGCACUU CUGAUGAGGCCGUUAGGCCGAA IGACAGCA 5575 1343 GCUGUCCC A AGUGCCAG 5072 CUGGCACU CUGAUGAGGCCGUUAGGCCGAA IGGACAGC 5576 1349 CCAAGUGC C AGUAUCAG 5073 CUGAUACU CUGAUGAGGCCGUUAGGCCGAA ICACUUGG 5577 1350 CAAGUGCC A GUAUCAGG 5074 CCUGAUAC CUGAUGAGGCCGUUAGGCCGAA IGCACUUG 5578 1356 CCAGUAUC A GGCCCCUG 5075 CAGGGGCC CUGAUGAGGCCGUUAGGCCGAA IAUACUGG 5579 1360 UAUCAGGC C CCUGAUAU 5076 AUAUCAGG CUGAUGAGGCCGUUAGGCCGAA ICCUGAUA 5580 1361 AUCAGGCC C CUGAUAUG 5077 CAUAUCAG CUGAUGAGGCCGUUAGGCCGAA IGCCUGAU 5581 1362 UCAGGCCC C UGAUAUGG 5078 CCAUAUCA CUGAUGAGGCCGUUAGGCCGAA IGGCCUGA 5582 1363 CAGGCCCC U GAUAUGGA 5079 UCCAUAUC CUGAUGAGGCCGUUAGGCCGAA IGGGCCUG 5583 1373 AUAUGGAC A CCCUGCAG 5080 CUGCAGGG CUGAUGAGGCCGUUAGGCCGAA IUCCAUAU 5584 1375 AUGGACAC C CUGCAGAU 5081 AUCUGCAG CUGAUGAGGCCGUUAGGCCGAA IUGUCCAU 5585 1376 UGGACACC C UGCAGAUA 5082 UAUCUGCA CUGAUGAGGCCGUUAGGCCGAA IGUGUCCA 5586 1377 GGACACCC U GCAGAUAC 5083 GUAUCUGC CUGAUGAGGCCGUUAGGCCGAA IGGUGUCC 5587 1380 CACCCUGC A GAUACAUG 5084 CAUGUAUC CUGAUGAGGCCGUUAGGCCGAA ICAGGGUG 5588 1386 GCAGAUAC A UGUCAUGG 5085 CCAUGACA CUGAUGAGGCCGUUAGGCCGAA IUAUCUGC 5589 1391 UACAUGUC A UGGAGUGC 5086 GCACUCCA CUGAUGAGGCCGUUAGGCCGAA IACAUGUA 5590 1400 UGGAGUGC A UUGAGUAG 5087 CUACUCAA CUGAUGAGGCCGUUAGGCCGAA ICACUCCA 5591 1412 AGUAGGGC C GGCCAGUG 5088 CACUGGCC CUGAUGAGGCCGUUAGGCCGAA ICCCUACU 5592 1416 GGGCCGGC C AGUGCAAG 5089 CUUGCACU CUGAUGAGGCCGUUAGGCCGAA ICCGGCCC 5593 1417 GGCCGGCC A GUGCAAGG 5090 CCUUGCAC CUGAUGAGGCCGUUAGGCCGAA IGCCGGCC 5594

1422 GCCAGUGC A AGGCCACU 5091 AGUGGCCU CUGAUGAGGCCGUUAGGCCGAA ICACUGGC 5595 1427 UGCAAGGC C ACUGCCUG 5092 CAGGCAGU CUGAUGAGGCCGUUAGGCCGAA ICCUUGCA 5596 1428 GCAAGGCC A CUGCCUGC 5093 GCAGGCAG CUGAUGAGGCCGUUAGGCCGAA IGCCUUGC 5597 1430 AAGGCCAC U GCCUGCCC 5094 GGGCAGGC CUGAUGAGGCCGUUAGGCCGAA IUGGCCUU 5598 1433 GCCACUGC C UGCCCGAG 5095 CUCGGGCA CUGAUGAGGCCGUUAGGCCGAA ICAGUGGC 5599 1434 CCACUGCC U GCCCGAGG 5096 CCUCGGGC CUGAUGAGGCCGUUAGGCCGAA IGCAGUGG 5600 1437 CUGCCUGC C CGAGGACG 5097 CGUCCUCG CUGAUGAGGCCGUUAGGCCGAA ICAGGCAG 5601 1438 UGCCUGCC C GAGGACGU 5098 ACGUCCUC CUGAUGAGGCCGUUAGGCCGAA IGCAGGCA 5602 1449 GGACGUGC C CGGGACCG 5099 CGGUCCCG CUGAUGAGGCCGUUAGGCCGAA ICACGUCC 5603 1450 GACGUGCC C GGGACCGU 5100 ACGGUCCC CUGAUGAGGCCGUUAGGCCGAA IGCACGUC 5604 1456 CCCGGGAC C GUGCAGUC 5101 GACUGCAC CUGAUGAGGCCGUUAGGCCGAA IUCCCGGG 5605 1461 GACCGUGC A GUCUGCGC 5102 GCGCAGAC CUGAUGAGGCCGUUAGGCCGAA ICACGGUC 5606 1465 GUGCAGUC U GCGCUUUC 5103 GAAAGCGC CUGAUGAGGCCGUUAGGCCGAA IACUGCAC 5607 1470 GUCUGCGC U UUCCUCUC 5104 GAGAGGAA CUGAUGAGGCCGUUAGGCCGAA ICGCAGAC 5608 1474 GCGCUUUC C UCUCCCGC 5105 GCGGGAGA CUGAUGAGGCCGUUAGGCCGAA IAAAGCGC 5609 1475 CGCUUUCC U CUCCCGCC 5106 GGCGGGAG CUGAUGAGGCCGUUAGGCCGAA IGAAAGCG 5610 1477 CUUUCCUC U CCCGCCUG 5107 CAGGCGGG CUGAUGAGGCCGUUAGGCCGAA IAGGAAAG 5611 1479 UUCCUCUC C CGCCUGCC 5108 GGCAGGCG CUGAUGAGGCCGUUAGGCCGAA IAGAGGAA 5612 1480 UCCUCUCC C GCCUGCCU 5109 AGGCAGGC CUGAUGAGGCCGUUAGGCCGAA IGAGAGGA 5613 1483 UCUCCCGC C UGCCUAGC 5110 GCUAGGCA CUGAUGAGGCCGUUAGGCCGAA ICGGGAGA 5614 1484 CUCCCGCC U GCCUAGCC 5111 GGCUAGGC CUGAUGAGGCCGUUAGGCCGAA IGCGGGAG 5615 1487 CCGCCUGC C UAGCCCAG 5112 CUGGGCUA CUGAUGAGGCCGUUAGGCCGAA ICAGGCGG 5616 1488 CGCCUGCC U AGCCCAGG 5113 CCUGGGCU CUGAUGAGGCCGUUAGGCCGAA IGCAGGCG 5617 1492 UGCCUAGC C CAGGAUGA 5114 UCAUCCUG CUGAUGAGGCCGUUAGGCCGAA ICUAGGCA 5618 1493 GCCUAGCC C AGGAUGAA 5115 UUCAUCCU CUGAUGAGGCCGUUAGGCCGAA IGCUAGGC 5619 1494 CCUAGCCC A GGAUGAAG 5116 CUUCAUCC CUGAUGAGGCCGUUAGGCCGAA IGGCUAGG 5620 1506 UGAAGGGC U GGGUGGCC 5117 GGCCACCC CUGAUGAGGCCGUUAGGCCGAA ICCCUUCA 5621 1514 UGGGUGGC C ACAACUGG 5118 CCAGUUGU CUGAUGAGGCCGUUAGGCCGAA ICCACCCA 5622 1515 GGGUGGCC A CAACUGGG 5119 CCCAGUUG CUGAUGAGGCCGUUAGGCCGAA IGCCACCC 5623 1517 GUGGCCAC A ACUGGGAU 5120 AUCCCAGU CUGAUGAGGCCGUUAGGCCGAA IUGGCCAC 5624 1520 GCCACAAC U GGGAUGCC 5121 GGCAUCCC CUGAUGAGGCCGUUAGGCCGAA IUUGUGGC 5625 1528 UGGGAUGC C ACCUGGAG 5122 CUCCAGGU CUGAUGAGGCCGUUAGGCCGAA ICAUCCCA 5626 1529 GGGAUGCC A CCUGGAGC 5123 GCUCCAGG CUGAUGAGGCCGUUAGGCCGAA IGCAUCCC 5627 1531 GAUGCCAC C UGGAGCCC 5124 GGGCUCCA CUGAUGAGGCCGUUAGGCCGAA IUGGCAUC 5628 1532 AUGCCACC U GGAGCCCC 5125 GGGGCUCC CUGAUGAGGCCGUUAGGCCGAA IGUGGCAU 5629 1538 CCUGGAGC C CCACCCAG 5126 CUGGGUGG CUGAUGAGGCCGUUAGGCCGAA ICUCCAGG 5630 1539 CUGGAGCC C CACCCAGG 5127 CCUGGGUG CUGAUGAGGCCGUUAGGCCGAA IGCUCCAG 5631 1540 UGGAGCCC C ACCCAGGA 5128 UCCUGGGU CUGAUGAGGCCGUUAGGCCGAA IGGCUCCA 5632 1541 GGAGCCCC A CCCAGGAG 5129 CUCCUGGG CUGAUGAGGCCGUUAGGCCGAA IGGGCUCC 5633 1543 AGCCCCAC C CAGGAGCU 5130 AGCUCCUG CUGAUGAGGCCGUUAGGCCGAA IUGGGGCU 5634 1544 GCCCCACC C AGGAGCUG 5131 CAGCUCCU CUGAUGAGGCCGUUAGGCCGAA IGUGGGGC 5635 1545 CCCCACCC A GGAGCUGG 5132 CCAGCUCC CUGAUGAGGCCGUUAGGCCGAA IGGUGGGG 5636 1551 CCAGGAGC U GGCCGCGG 5133 CCGCGGCC CUGAUGAGGCCGUUAGGCCGAA ICUCCUGG 5637 1555 GAGCUGGC C GCGGCACC 5134 GGUGCCGC CUGAUGAGGCCGUUAGGCCGAA ICCAGCUC 5638 1561 GCCGCGGC A CCUUACGC 5135 GCGUAAGG CUGAUGAGGCCGUUAGGCCGAA ICCGCGGC 5639 1563 CGCGGCAC C UUACGCUU 5136 AAGCGUAA CUGAUGAGGCCGUUAGGCCGAA IUGCCGCG 5640 1564 GCGGCACC U UACGCUUC 5137 GAAGCGUA CUGAUGAGGCCGUUAGGCCGAA IGUGCCGC 5641 1570 CCUUACGC U UCAGCUGU 5138 ACAGCUGA CUGAUGAGGCCGUUAGGCCGAA ICGUAAGG 5642 1573 UACGCUUC A GCUGUUGA 5139 UCAACAGC CUGAUGAGGCCGUUAGGCCGAA IAAGCGUA 5643 1576 GCUUCAGC U GUUGAUCC 5140 GGAUCAAC CUGAUGAGGCCGUUAGGCCGAA ICUGAAGC 5644 1584 UGUUGAUC C GCUGGUCC 5141 GGACCAGC CUGAUGAGGCCGUUAGGCCGAA IAUCAACA 5645 1587 UGAUCCGC U GGUCCCCU 5142 AGGGGACC CUGAUGAGGCCGUUAGGCCGAA ICGGAUCA 5646 1592 CGCUGGUC C CCUCUUUU 5143 AAAAGAGG CUGAUGAGGCCGUUAGGCCGAA IACCAGCG 5647 1593 GCUGGUCC C CUCUUUUG 5144 CAAAAGAG CUGAUGAGGCCGUUAGGCCGAA IGACCAGC 5648 1594 CUGGUCCC C UCUUUUGG 5145 CCAAAAGA CUGAUGAGGCCGUUAGGCCGAA IGGACCAG 5649 1595 UGGUCCCC U CUUUUGGG 5146 CCCAAAAG CUGAUGAGGCCGUUAGGCCGAA IGGGACCA 5650 1597 GUCCCCUC U UUUGGGGU 5147 ACCCCAAA CUGAUGAGGCCGUUAGGCCGAA IAGGGGAC 5651 1615 GAUGCGGC C CCGAUCAG 5148 CUGAUCGG CUGAUGAGGCCGUUAGGCCGAA ICCGCAUC 5652 1616 AUGCGGCC C CGAUCAGG 5149 CCUGAUCG CUGAUGAGGCCGUUAGGCCGAA IGCCGCAU 5653 1617 UGCGGCCC C GAUCAGGC 5150 GCCUGAUC CUGAUGAGGCCGUUAGGCCGAA IGGCCGCA 5654 1622 CCCCGAUC A GGCCUGAC 5151 GUCAGGCC CUGAUGAGGCCGUUAGGCCGAA IAUCGGGG 5655 1626 GAUCAGGC C UGACUCGC 5152 GCGAGUCA CUGAUGAGGCCGUUAGGCCGAA ICCUGAUC 5656 1627 AUCAGGCC U GACUCGCU 5153 AGCGAGUC CUGAUGAGGCCGUUAGGCCGAA IGCCUGAU 5657 1631 GGCCUGAC U CGCUGCUC 5154 GAGCAGCG CUGAUGAGGCCGUUAGGCCGAA IUCAGGCC 5658 1635 UGACUCGC U GCUCUUUU 5155 AAAAGAGC CUGAUGAGGCCGUUAGGCCGAA ICGAGUCA 5659 1638 CUCGCUGC U CUUUUUGU 5156 ACAAAAAG CUGAUGAGGCCGUUAGGCCGAA ICAGCGAG 5660 1640 CGCUGCUC U UUUUGUUC 5157 GAACAAAA CUGAUGAGGCCGUUAGGCCGAA IAGCAGCG 5661 1649 UUUUGUUC C CUUCUGUC 5158 GACAGAAG CUGAUGAGGCCGUUAGGCCGAA IAACAAAA 5662 1650 UUUGUUCC C UUCUGUCU 5159 AGACAGAA CUGAUGAGGCCGUUAGGCCGAA IGAACAAA 5663 1651 UUGUUCCC U UCUGUCUG 5160 CAGACAGA CUGAUGAGGCCGUUAGGCCGAA IGGAACAA 5664 1654 UUCCCUUC U GUCUGCUC 5161 GAGCAGAC CUGAUGAGGCCGUUAGGCCGAA IAAGGGAA 5665 1658 CUUCUGUC U GCUCGAAC 5162 GUUCGAGC CUGAUGAGGCCGUUAGGCCGAA IACAGAAG 5666 1661 CUGUCUGC U CGAACCAC 5163 GUGGUUCG CUGAUGAGGCCGUUAGGCCGAA ICAGACAG 5667 1667 GCUCGAAC C ACUUGCCU 5164 AGGCAAGU CUGAUGAGGCCGUUAGGCCGAA IUUCGAGC 5668 1668 CUCGAACC A CUUGCCUC 5165 GAGGCAAG CUGAUGAGGCCGUUAGGCCGAA IGUUCGAG 5669 1670 CGAACCAC U UGCCUCGG 5166 CCGAGGCA CUGAUGAGGCCGUUAGGCCGAA IUGGUUCG 5670 1674 CCACUUGC C UCGGGCUA 5167 UAGCCCGA CUGAUGAGGCCGUUAGGCCGAA ICAAGUGG 5671 1675 CACUUGCC U CGGGCUAA 5168 UUAGCCCG CUGAUGAGGCCGUUAGGCCGAA IGCAAGUG 5672 1681 CCUCGGGC U AAUCCCUC 5169 GAGGGAUU CUGAUGAGGCCGUUAGGCCGAA ICCCGAGG 5673 1686 GGCUAAUC C CUCCCUCU 5170 AGAGGGAG CUGAUGAGGCCGUUAGGCCGAA IAUUAGCC 5674 1687 GCUAAUCC C UCCCUCUU 5171 AAGAGGGA CUGAUGAGGCCGUUAGGCCGAA IGAUUAGC 5675 1688 CUAAUCCC U CCCUCUUC 5172 GAAGAGGG CUGAUGAGGCCGUUAGGCCGAA IGGAUUAG 5676 1690 AAUCCCUC C CUCUUCCU 5173 AGGAAGAG CUGAUGAGGCCGUUAGGCCGAA IAGGGAUU 5677 1691 AUCCCUCC C UCUUCCUC 5174 GAGGAAGA CUGAUGAGGCCGUUAGGCCGAA IGAGGGAU

5678 1692 UCCCUCCC U CUUCCUCC 5175 GGAGGAAG CUGAUGAGGCCGUUAGGCCGAA IGGAGGGA 5679 1694 CCUCCCUC U UCCUCCAC 5176 GUGGAGGA CUGAUGAGGCCGUUAGGCCGAA IAGGGAGG 5680 1697 CCCUCUUC C UCCACCCG 5177 CGGGUGGA CUGAUGAGGCCGUUAGGCCGAA IAAGAGGG 5681 1698 CCUCUUCC U CCACCCGG 5178 CCGGGUGG CUGAUGAGGCCGUUAGGCCGAA IGAAGAGG 5682 1700 UCUUCCUC C ACCCGGCA 5179 UGCCGGGU CUGAUGAGGCCGUUAGGCCGAA IAGGAAGA 5683 1701 CUUCCUCC A CCCGGCAC 5180 GUGCCGGG CUGAUGAGGCCGUUAGGCCGAA IGAGGAAG 5684 1703 UCCUCCAC C CGGCACUG 5181 CAGUGCCG CUGAUGAGGCCGUUAGGCCGAA IUGGAGGA 5685 1704 CCUCCACC C GGCACUGG 5182 CCAGUGCC CUGAUGAGGCCGUUAGGCCGAA IGUGGAGG 5686 1708 CACCCGGC A CUGGGGAA 5183 UUCCCCAG CUGAUGAGGCCGUUAGGCCGAA ICCGGGUG 5687 1710 CCCGGCAC U GGGGAAGU 5184 ACUUCCCC CUGAUGAGGCCGUUAGGCCGAA IUGCCGGG 5688 1720 GGGAAGUC A AGAAUGGG 5185 CCCAUUCU CUGAUGAGGCCGUUAGGCCGAA IACUUCCC 5689 1731 AAUGGGGC C UGGGGCUC 5186 GAGCCCCA CUGAUGAGGCCGUUAGGCCGAA ICCCCAUU 5690 1732 AUGGGGCC U GGGGCUCU 5187 AGAGCCCC CUGAUGAGGCCGUUAGGCCGAA IGCCCCAU 5691 1738 CCUGGGGC U CUCAGGGA 5188 UCCCUGAG CUGAUGAGGCCGUUAGGCCGAA ICCCCAGG 5692 1740 UGGGGCUC U CAGGGAGA 5189 UCUCCCUG CUGAUGAGGCCGUUAGGCCGAA IAGCCCCA 5693 1742 GGGCUCUC A GGGAGAAC 5190 GUUCUCCC CUGAUGAGGCCGUUAGGCCGAA IAGAGCCC 5694 1751 GGGAGAAC U GCUUCCCC 5191 GGGGAAGC CUGAUGAGGCCGUUAGGCCGAA IUUCUCCC 5695 1754 AGAACUGC U UCCCCUGG 5192 CCAGGGGA CUGAUGAGGCCGUUAGGCCGAA ICAGUUCU 5696 1757 ACUGCUUC C CCUGGCAG 5193 CUGCCAGG CUGAUGAGGCCGUUAGGCCGAA IAAGCAGU 5697 1758 CUGCUUCC C CUGGCAGA 5194 UCUGCCAG CUGAUGAGGCCGUUAGGCCGAA IGAAGCAG 5698 1759 UGCUUCCC C UGGCAGAG 5195 CUCUGCCA CUGAUGAGGCCGUUAGGCCGAA IGGAAGCA 5699 1760 GCUUCCCC U GGCAGAGC 5196 GCUCUGCC CUGAUGAGGCCGUUAGGCCGAA IGGGAAGC 5700 1764 CCCCUGGC A GAGCUGGG 5197 CCCAGCUC CUGAUGAGGCCGUUAGGCCGAA ICCAGGGG 5701 1769 GGCAGAGC U GGGUGGCA 5198 UGCCACCC CUGAUGAGGCCGUUAGGCCGAA ICUCUGCC 5702 1777 UGGGUGGC A GCUCUUCC 5199 GGAAGAGC CUGAUGAGGCCGUUAGGCCGAA ICCACCCA 5703 1780 GUGGCAGC U CUUCCUCC 5200 GGAGGAAG CUGAUGAGGCCGUUAGGCCGAA ICUGCCAC 5704 1782 GGCAGCUC U UCCUCCCA 5201 UGGGAGGA CUGAUGAGGCCGUUAGGCCGAA IAGCUGCC 5705 1785 AGCUCUUC C UCCCACCG 5202 CGGUGGGA CUGAUGAGGCCGUUAGGCCGAA IAAGAGCU 5706 1786 GCUCUUCC U CCCACCGG 5203 CCGGUGGG CUGAUGAGGCCGUUAGGCCGAA IGAAGAGC 5707 1788 UCUUCCUC C CACCGGAC 5204 GUCCGGUG CUGAUGAGGCCGUUAGGCCGAA IAGGAAGA 5708 1789 CUUCCUCC C ACCGGACA 5205 UGUCCGGU CUGAUGAGGCCGUUAGGCCGAA IGAGGAAG 5709 1790 UUCCUCCC A CCGGACAC 5206 GUGUCCGG CUGAUGAGGCCGUUAGGCCGAA IGGAGGAA 5710 1792 CCUCCCAC C GGACACCG 5207 CGGUGUCC CUGAUGAGGCCGUUAGGCCGAA IUGGGAGG 5711 1797 CACCGGAC A CCGACCCG 5208 CGGGUCGG CUGAUGAGGCCGUUAGGCCGAA IUCCGGUG 5712 1799 CCGGACAC C GACCCGCC 5209 GGCGGGUC CUGAUGAGGCCGUUAGGCCGAA IUGUCCGG 5713 1803 ACACCGAC C CGCCCGCC 5210 GGCGGGCG CUGAUGAGGCCGUUAGGCCGAA IUCGGUGU 5714 1804 CACCGACC C GCCCGCCG 5211 CGGCGGGC CUGAUGAGGCCGUUAGGCCGAA IGUCGGUG 5715 1807 CGACCCGC C CGCCGCUG 5212 CAGCGGCG CUGAUGAGGCCGUUAGGCCGAA ICGGGUCG 5716 1808 GACCCGCC C GCCGCUGU 5213 ACAGCGGC CUGAUGAGGCCGUUAGGCCGAA IGCGGGUC 5717 1811 CCGCCCGC C GCUGUGCC 5214 GGCACAGC CUGAUGAGGCCGUUAGGCCGAA ICGGGCGG 5718 1814 CCCGCCGC U GUGCCCUG 5215 CAGGGCAC CUGAUGAGGCCGUUAGGCCGAA ICGGCGGG 5719 1819 CGCUGUGC C CUGGGAGU 5216 ACUCCCAG CUGAUGAGGCCGUUAGGCCGAA ICACAGCG 5720 1820 GCUGUGCC C UGGGAGUG 5217 CACUCCCA CUGAUGAGGCCGUUAGGCCGAA IGCACAGC 5721 1821 CUGUGCCC U GGGAGUGC 5218 GCACUCCC CUGAUGAGGCCGUUAGGCCGAA IGGCACAG 5722 1830 GGGAGUGC U GCCCUCUU 5219 AAGAGGGC CUGAUGAGGCCGUUAGGCCGAA ICACUCCC 5723 1833 AGUGCUGC C CUCUUACC 5220 GGUAAGAG CUGAUGAGGCCGUUAGGCCGAA ICAGCACU 5724 1834 GUGCUGCC C UCUUACCA 5221 UGGUAAGA CUGAUGAGGCCGUUAGGCCGAA IGCAGCAC 5725 1835 UGCUGCCC U CUUACCAU 5222 AUGGUAAG CUGAUGAGGCCGUUAGGCCGAA IGGCAGCA 5726 1837 CUGCCCUC U UACCAUGC 5223 GCAUGGUA CUGAUGAGGCCGUUAGGCCGAA IAGGGCAG 5727 1841 CCUCUUAC C AUGCACAC 5224 GUGUGCAU CUGAUGAGGCCGUUAGGCCGAA IUAAGAGG 5728 1842 CUCUUACC A UGCACACG 5225 CGUGUGCA CUGAUGAGGCCGUUAGGCCGAA IGUAAGAG 5729 1846 UACCAUGC A CACGGGUG 5226 CACCCGUG CUGAUGAGGCCGUUAGGCCGAA ICAUGGUA 5730 1848 CCAUGCAC A CGGGUGCU 5227 AGCACCCG CUGAUGAGGCCGUUAGGCCGAA IUGCAUGG 5731 1856 ACGGGUGC U CUCCUUUU 5228 AAAAGGAG CUGAUGAGGCCGUUAGGCCGAA ICACCCGU 5732 1858 GGGUGCUC U CCUUUUGG 5229 CCAAAAGG CUGAUGAGGCCGUUAGGCCGAA IAGCACCC 5733 1860 GUGCUCUC C UUUUGGGC 5230 GCCCAAAA CUGAUGAGGCCGUUAGGCCGAA IAGAGCAC 5734 1861 UGCUCUCC U UUUGGGCU 5231 AGCCCAAA CUGAUGAGGCCGUUAGGCCGAA IGAGAGCA 5735 1869 UUUUGGGC U GCAUGCUA 5232 UAGCAUGC CUGAUGAGGCCGUUAGGCCGAA ICCCAAAA 5736 1872 UGGGCUGC A UGCUAUUC 5233 GAAUAGCA CUGAUGAGGCCGUUAGGCCGAA ICAGCCCA 5737 1876 CUGCAUGC U AUUCCAUU 5234 AAUGGAAU CUGAUGAGGCCGUUAGGCCGAA ICAUGCAG 5738 1881 UGCUAUUC C AUUUUGCA 5235 UGCAAAAU CUGAUGAGGCCGUUAGGCCGAA IAAUAGCA 5739 1882 GCUAUUCC A UUUUGCAG 5236 CUGCAAAA CUGAUGAGGCCGUUAGGCCGAA IGAAUAGC 5740 1889 CAUUUUGC A GCCAGACC 5237 GGUCUGGC CUGAUGAGGCCGUUAGGCCGAA ICAAAAUG 5741 1892 UUUGCAGC C AGACCGAU 5238 AUCGGUCU CUGAUGAGGCCGUUAGGCCGAA ICUGCAAA 5742 1893 UUGCAGCC A GACCGAUG 5239 CAUCGGUC CUGAUGAGGCCGUUAGGCCGAA IGCUGCAA 5743 1897 AGCCAGAC C GAUGUGUA 5240 UACACAUC CUGAUGAGGCCGUUAGGCCGAA IUCUGGCU 5744 1912 UAUUUAAC C AGUCACUA 5241 UAGUGACU CUGAUGAGGCCGUUAGGCCGAA IUUAAAUA 5745 1913 AUUUAACC A GUCACUAU 5242 AUAGUGAC CUGAUGAGGCCGUUAGGCCGAA IGUUAAAU 5746 1917 AACCAGUC A CUAUUGAU 5243 AUCAAUAG CUGAUGAGGCCGUUAGGCCGAA IACUGGUU 5747 1919 CCAGUCAC U AUUGAUGG 5244 CCAUCAAU CUGAUGAGGCCGUUAGGCCGAA IUGACUGG 5748 1930 UGAUGGAC A UUUGGGUU 5245 AACCCAAA CUGAUGAGGCCGUUAGGCCGAA IUCCAUCA 5749 1944 GUUGUUUC C CAUCUUUU 5246 AAAAGAUG CUGAUGAGGCCGUUAGGCCGAA IAAACAAC 5750 1945 UUGUUUCC C AUCUUUUU 5247 AAAAAGAU CUGAUGAGGCCGUUAGGCCGAA IGAAACAA 5751 1946 UGUUUCCC A UCUUUUUG 5248 CAAAAAGA CUGAUGAGGCCGUUAGGCCGAA IGGAAACA 5752 1949 UUCCCAUC U UUUUGUUA 5249 UAACAAAA CUGAUGAGGCCGUUAGGCCGAA IAUGGGAA 5753 1959 UUUGUUAC C AUAAAUAA 5250 UUAUUUAU CUGAUGAGGCCGUUAGGCCGAA IUAACAAA 5754 1960 UUGUUACC A UAAAUAAU 5251 AUUAUUUA CUGAUGAGGCCGUUAGGCCGAA IGUAACAA 5755 1972 AUAAUGGC A UAGUAAAA 5252 UUUUACUA CUGAUGAGGCCGUUAGGCCGAA ICCAUUAU 5756 Input Sequence = NM_003639. Cut Site = CH/. Arm Length = 8. Core Sequence = CUGAUGAG GCCGUUAGGC CGAA NM_003639 (Homo sapiens inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase gamma (IKBKG), mRNA.; 1994 bp) Underlined region can be any X sequence or linker, as described herein. "I" stands for Inosine.

[0267] TABLE-US-00005 TABLE V Human IKK-gamma Zinzyme and Substrate Sequence Seq Seq Pos Substrate ID Zinzyme ID 13 CGAGCAUG G CCCUUGUG 5757 CACAAGGG GCCGAAAGGCGAGUGAGGUCU CAUGCUCG 6034 19 UGGCCCUU G UGAUCCAG 5758 CUGGAUCA GCCGAAAGGCGAGUGAGGUCU AAGGGCCA 6035 28 UGAUCCAG G UGGGGAAA 5759 UUUCCCCA GCCGAAAGGCGAGUGAGGUCU CUGGAUCA 6036 42 AAACUAAG G CCCAGAGA 5760 UCUCUGGG GCCGAAAGGCGAGUGAGGUCU CUUAGUUU 6037 52 CCAGAGAA G UGAGGACC 5761 GGUCCUCA GCCGAAAGGCGAGUGAGGUCU UUCUCUGG 6038 63 AGGACCCC G CAGACUAU 5762 AUAGUCUG GCCGAAAGGCGAGUGAGGUCU GGGGUCCU 6039 80 CAAUCCCA G UCUCUUCC 5763 GGAAGAGA GCCGAAAGGCGAGUGAGGUCU UGGGAUUG 6040 100 CACUCCCU G UGAAGCUC 5764 GAGCUUCA GCCGAAAGGCGAGUGAGGUCU AGGGAGUG 6041 105 CCUGUGAA G CUCUCCAG 5765 CUGGAGAG GCCGAAAGGCGAGUGAGGUCU UUCACAGG 6042 113 GCUCUCCA G CAUCAUCG 5766 CGAUGAUG GCCGAAAGGCGAGUGAGGUCU UGGAGAGC 6043 124 UCAUCGAG G UCCCAUCA 5767 UGAUGGGA GCCGAAAGGCGAGUGAGGUCU CUCGAUGA 6044 133 UCCCAUCA G CCCUUGCC 5768 GGCAAGGG GCCGAAAGGCGAGUGAGGUCU UGAUGGGA 6045 139 CAGCCCUU G CCCUGUUG 5769 CAACAGGG GCCGAAAGGCGAGUGAGGUCU AAGGGCUG 6046 144 CUUGCCCU G UUGGAUGA 5770 UCAUCCAA GCCGAAAGGCGAGUGAGGUCU AGGGCAAG 6047 157 AUGAAUAG G CACCUCUG 5771 CAGAGGUG GCCGAAAGGCGAGUGAGGUCU CUAUUCAU 6046 171 CUGGAAGA G CCAACUGU 5772 ACAGUUGG GCCGAAAGGCGAGUGAGGUCU UCUUCCAG 6049 178 AGCCAACU G UGUGAGAU 5773 AUCUCACA GCCGAAAGGCGAGUGAGGUCU AGUUGGCU 6050 180 CCAACUGU G UGAGAUGG 5774 CCAUCUCA GCCGAAAGGCGAGUGAGGUCU ACAGUUGG 6051 188 GUGAGAUG G UGCAGCCC 5775 GGGCUGCA GCCGAAAGGCGAGUGAGGUCU CAUCUCAC 6052 190 GAGAUGGU G CAGCCCAG 5776 CUGGGCUG GCCGAAAGGCGAGUGAGGUCU ACCAUCUC 6053 193 AUGGUGCA G CCCAGUGG 5777 CCACUGGG GCCGAAAGGCGAGUGAGGUCU UGCACCAU 6054 198 GCAGCCCA G UGGUGGCC 5778 GGCCACCA GCCGAAAGGCGAGUGAGGUCU UGGGCUGC 6055 201 GCCCAGUG G UGGCCCGG 5779 CCGGGCCA GCCGAAAGGCGAGUGAGGUCU CACUGGGC 6056 204 CAGUGGUG G CCCGGCAG 5780 CUGCCGGG GCCGAAAGGCGAGUGAGGUCU CACCACUG 6057 209 GUGGCCCG G CAGCAGAU 5781 AUCUGCUG GCCGAAAGGCGAGUGAGGUCU CGGGCCAC 6058 212 GCCCGGCA G CAGAUCAG 5782 CUGAUCUG GCCGAAAGGCGAGUGAGGUCU UGCCGGGC 6059 224 AUCAGGAC G UACUGGGC 5783 GCCCAGUA GCCGAAAGGCGAGUGAGGUCU GUCCUGAU 6060 231 CGUACUGG G CGAAGAGU 5784 ACUCUUCG GCCGAAAGGCGAGUGAGGUCU CCAGUACG 6061 238 GGCGAAGA G UCUCCUCU 5785 AGAGGAGA GCCGAAAGGCGAGUGAGGUCU UCUUCGCC 6062 253 CUGGGGAA G CCAGCCAU 5786 AUGGCUGG GCCGAAAGGCGAGUGAGGUCU UUCCCCAG 6063 257 GGAAGCCA G CCAUGCUG 5787 CAGCAUGG GCCGAAAGGCGAGUGAGGUCU UGGCUUCC 6064 262 CCAGCCAU G CUGCACCU 5788 AGGUGCAG GCCGAAAGGCGAGUGAGGUCU AUGGCUGG 6065 265 GCCAUGCU G CACCUGCC 5789 GGCAGGUG GCCGAAAGGCGAGUGAGGUCU AGCAUGGC 6066 271 CUGCACCU G CCUUCAGA 5790 UCUGAAGG GCCGAAAGGCGAGUGAGGUCU AGGUGCAG 6067 285 AGAACAGG G CGCUCCUG 5791 CAGGAGCG GCCGAAAGGCGAGUGAGGUCU CCUGUUCU 6068 287 AACAGGGC G CUCCUGAG 5792 CUCAGGAG GCCGAAAGGCGAGUGAGGUCU GCCCUGUU 6069 304 ACCCUCCA G CGCUGCCU 5793 AGGCAGCG GCCGAAAGGCGAGUGAGGUCU UGGAGGGU 6070 306 CCUCCAGC G CUGCCUGG 5794 CCAGGCAG GCCGAAAGGCGAGUGAGGUCU GCUGGAGG 6071 309 CCAGCGCU G CCUGGAGG 5795 CCUCCAGG GCCGAAAGGCGAGUGAGGUCU AGCGCUGG 6072 328 AAUCAAGA G CUCCGAGA 5796 UCUCGGAG GCCGAAAGGCGAGUGAGGUCU UCUUGAUU 6073 338 UCCGAGAU G CCAUCCGG 5797 CCGGAUGG GCCGAAAGGCGAGUGAGGUCU AUCUCGGA 6074 346 GCCAUCCG G CAGAGCAA 5798 UUGCUCUG GCCGAAAGGCGAGUGAGGUCU CGGAUGGC 6075 351 CCGGCAGA G CAACCAGA 5799 UCUGGUUG GCCGAAAGGCGAGUGAGGUCU UCUGCCGG 6076 364 CAGAUUCU G CGGGAGCG 5800 CGCUCCCG GCCGAAAGGCGAGUGAGGUCU AGAAUCUG 6077 370 CUGCGGGA G CGCUGCGA 5801 UCGCAGCG GCCGAAAGGCGAGUGAGGUCU UCCCGCAG 6078 372 GCGGGAGC G CUGCGAGG 5802 CCUCGCAG GCCGAAAGGCGAGUGAGGUCU GCUCCCGC 6079 375 GGAGCGCU G CGAGGAGC 5803 GCUCCUCG GCCGAAAGGCGAGUGAGGUCU AGCGCUCC 6080 382 UGCGAGGA G CUUCUGCA 5804 UGCAGAAG GCCGAAAGGCGAGUGAGGUCU UCCUCGCA 6081 388 GAGCUUCU G CAUUUCCA 5805 UGGAAAUG GCCGAAAGGCGAGUGAGGUCU AGAAGCUC 6082 398 AUUUCCAA G CCAGCCAG 5806 CUGGCUGG GCCGAAAGGCGAGUGAGGUCU UUGGAAAU 6083 402 CCAAGCCA G CCAGAGGG 5807 CCCUCUGG GCCGAAAGGCGAGUGAGGUCU UGGCUUGG 6084 421 GAGAAGGA G UUCCUCAU 5808 AUGAGGAA GCCGAAAGGCGAGUGAGGUCU UCCUUCUC 6085 430 UUCCUCAU G UGCAAGUU 5809 AACUUGCA GCCGAAAGGCGAGUGAGGUCU AUGAGGAA 6086 432 CCUCAUGU G CAAGUUCC 5810 GGAACUUG GCCGAAAGGCGAGUGAGGUCU ACAUGAGG 6087 436 AUGUGCAA G UUCCAGGA 5811 UCCUGGAA GCCGAAAGGCGAGUGAGGUCU UUGCACAU 6088 446 UCCAGGAG G CCAGGAAA 5812 UUUCCUGG GCCGAAAGGCGAGUGAGGUCU CUCCUGGA 6089 458 GGAAACUG G UGGAGAGA 5813 UCUCUCCA GCCGAAAGGCGAGUGAGGUCU CAGUUUCC 6090 471 GAGACUCG G CCUGGAGA 5814 UCUCCAGG GCCGAAAGGCGAGUGAGGUCU CGAGUCUC 6091 481 CUGGAGAA G CUCGAUCU 5815 AGAUCGAG GCCGAAAGGCGAGUGAGGUCU UUCUCCAG 6092 496 CUGAAGAG G CAGAAGGA 5816 UCCUUCUG GCCGAAAGGCGAGUGAGGUCU CUCUUCAG 6093 505 CAGAAGGA G CAGGCUCU 5817 AGAGCCUG GCCGAAAGGCGAGUGAGGUCU UCCUUCUG 6094 509 AGGAGCAG G CUCUGCGG 5818 CCGCAGAG GCCGAAAGGCGAGUGAGGUCU CUGCUCCU 6095 514 CAGGCUCU G CGGGAGGU 5819 ACCUCCCG GCCGAAAGGCGAGUGAGGUCU AGAGCCUG 6096 521 UGCGGGAG G UGGAGCAC 5820 GUGCUCCA GCCGAAAGGCGAGUGAGGUCU CUCCCGCA 6097 526 GAGGUGGA G CACCUGAA 5821 UUCAGGUG GCCGAAAGGCGAGUGAGGUCU UCCACCUC 6098 540 GAAGAGAU G CCAGCAGC 5822 GCUGCUGG GCCGAAAGGCGAGUGAGGUCU AUCUCUUC 6099 544 AGAUGCCA G CAGCAGAU 5823 AUCUGCUG GCCGAAAGGCGAGUGAGGUCU UGGCAUCU 6100 547 UGCCAGCA G CAGAUGGC 5824 GCCAUCUG GCCGAAAGGCGAGUGAGGUCU UGCUGGCA 6101 554 AGCAGAUG G CUGAGGAC 5825 GUCCUCAG GCCGAAAGGCGAGUGAGGUCU CAUCUGCU 6102 566 AGGACAAG G CCUCUGUG 5826 CACAGAGG GCCGAAAGGCGAGUGAGGUCU CUUGUCCU 6103 572 AGGCCUCU G UGAAAGCC 5827 GGCUUUCA GCCGAAAGGCGAGUGAGGUCU AGAGGCCU 6104 578 CUGUGAAA G CCCAGGUG 5828 CACCUGGG GCCGAAAGGCGAGUGAGGUCU UUUCACAG 6105 584 AAGCCCAG G UGACGUCC 5829 GGACGUCA GCCGAAAGGCGAGUGAGGUCU CUGGGCUU 6106 589 CAGGUGAC G UCCUUGCU 5830 AGCAAGGA GCCGAAAGGCGAGUGAGGUCU GUCACCUG 6107 595 ACGUCCUU G CUCGGGGA 5831 UCCCCGAG GCCGAAAGGCGAGUGAGGUCU AAGGACGU 6108 604 CUCGGGGA G CUGCAGGA 5832 UCCUGCAG GCCGAAAGGCGAGUGAGGUCU UCCCCGAG 6109 607 GGGGAGCU G CAGGAGAG 5833 CUCUCCUG GCCGAAAGGCGAGUGAGGUCU AGCUCCCC 6110 615 GCAGGAGA G CCAGAGUC 5834 GACUCUGG GCCGAAAGGCGAGUGAGGUCU UCUCCUGC 6111 621 GAGCCAGA G UCGCUUGG 5835 CCAAGCGA GCCGAAAGGCGAGUGAGGUCU UCUGGCUC 6112 624 CCAGAGUC G CUUGGAGG 5836 CCUCCAAG GCCGAAAGGCGAGUGAGGUCU GACUCUGG 6113 632 GCUUGGAG G CUGCCACU 5837 AGUGGCAG GCCGAAAGGCGAGUGAGGUCU CUCCAAGC 6114 635 UGGAGGCU G CCACUAAG 5838 CUUAGUGG GCCGAAAGGCGAGUGAGGUCU AGCCUCCA 6115 648 UAAGGAAU G CCAGGCUC 5839 GAGCCUGG GCCGAAAGGCGAGUGAGGUCU AUUCCUUA 6116 653 AAUGCCAG G CUCUGGAG 5840 CUCCAGAG GCCGAAAGGCGAGUGAGGUCU CUGGCAUU 6117 663 UCUGGAGG G UCGGGCCC 5841 GGGCCCGA GCCGAAAGGCGAGUGAGGUCU CCUCCAGA 6118 668 AGGGUCGG G CCCGGGCG 5842 CGCCCGGG GCCGAAAGGCGAGUGAGGUCU CCGACCCU 6119 674 GGGCCCGG G CGGCCAGC 5843 GCUGGCCG GCCGAAAGGCGAGUGAGGUCU CCGGGCCC 6120 677 CCCGGGCG G CCAGCGAG 5844 CUCGCUGG GCCGAAAGGCGAGUGAGGUCU CGCCCGGG 6121 681 GGCGGCCA G CGAGCAGG 5845 CCUGCUCG GCCGAAAGGCGAGUGAGGUCU UGGCCGCC 6122 685 GCCAGCGA G CAGGCGCG 5846 CGCGCCUG GCCGAAAGGCGAGUGAGGUCU UCGCUGGC 6123 689 GCGAGCAG G CGCGGCAG 5847 CUGCCGCG GCCGAAAGGCGAGUGAGGUCU CUGCUCGC 6124 691 GAGCAGGC G CGGCAGCU 5848 AGCUGCCG GCCGAAAGGCGAGUGAGGUCU GCCUGCUC 6125 694 CAGGCGCG G CAGCUGGA 5849 UCCAGCUG GCCGAAAGGCGAGUGAGGUCU CGCGCCUG 6126 697 GCGCGGCA G CUGGAGAG 5850 CUCUCCAG GCCGAAAGGCGAGUGAGGUCU UGCCGCGC 6127 705 GCUGGAGA G UGAGCGCG 5851 CGCGCUCA GCCGAAAGGCGAGUGAGGUCU UCUCCAGC 6128 709 GAGAGUGA G CGCGAGGC 5852 GCCUCGCG GCCGAAAGGCGAGUGAGGUCU UCACUCUC 6129 711 GAGUGAGC G CGAGGCGC 5853 GCGCCUCG GCCGAAAGGCGAGUGAGGUCU GCUCACUC 6130 716 AGCGCGAG G CGCUGCAG 5854 CUGCAGCG GCCGAAAGGCGAGUGAGGUCU CUCGCGCU 6131 718 CGCGAGGC G CUGCAGCA 5855 UGCUGCAG GCCGAAAGGCGAGUGAGGUCU GCCUCGCG 6132 721 GAGGCGCU G CAGCAGCA 5856 UGCUGCUG GCCGAAAGGCGAGUGAGGUCU AGCGCCUC 6133 724 GCGCUGCA G CAGCAGCA 5857 UGCUGCUG GCCGAAAGGCGAGUGAGGUCU UGCAGCGC 6134 727 CUGCAGCA G CAGCACAG 5858 CUGUGCUG GCCGAAAGGCGAGUGAGGUCU UGCUGCAG 6135 730 CAGCAGCA G CACAGCGU 5859 ACGCUGUG GCCGAAAGGCGAGUGAGGUCU UGCUGCUG 6136 735 GCAGCACA G CGUGCAGG 5860 CCUGCACG GCCGAAAGGCGAGUGAGGUCU UGUGCUGC 6137 737 AGCACAGC G UGCAGGUG 5861 CACCUGCA GCCGAAAGGCGAGUGAGGUCU GCUGUGCU 6138 739 CACAGCGU G CAGGUGGA 5862 UCCACCUG GCCGAAAGGCGAGUGAGGUCU ACGCUGUG 6139 743 GCGUGCAG G UGGACCAG 5863 CUGGUCCA GCCGAAAGGCGAGUGAGGUCU CUGCACGC 6140 751 GUGGACCA G CUGCGCAU 5864 AUGCGCAG GCCGAAAGGCGAGUGAGGUCU UGGUCCAC 6141 754 GACCAGCU G CGCAUGCA 5865 UGCAUGCG GCCGAAAGGCGAGUGAGGUCU AGCUGGUC 6142 756 CCAGCUGC G CAUGCAGG 5866 CCUGCAUG GCCGAAAGGCGAGUGAGGUCU GCAGCUGG 6143 760 CUGCGCAU G CAGGGCCA 5867 UGGCCCUG GCCGAAAGGCGAGUGAGGUCU AUGCGCAG 6144 765 CAUGCAGG G CCAGAGCG 5868 CGCUCUGG GCCGAAAGGCGAGUGAGGUCU CCUGCAUG 6145 771 GGGCCAGA G CGUGGAGG 5869 CCUCCACG GCCGAAAGGCGAGUGAGGUCU UCUGGCCC 6146 773 GCCAGAGC G UGGAGGCC 5870 GGCCUCCA GCCGAAAGGCGAGUGAGGUCU GCUCUGGC 6147 779 GCGUGGAG G CCGCGCUC 5871 GAGCGCGG GCCGAAAGGCGAGUGAGGUCU CUCCACGC 6148 782 UGGAGGCC G CGCUCCGC 5872 GCGGAGCG GCCGAAAGGCGAGUGAGGUCU GGCCUCCA 6149 784 GAGGCCGC G CUCCGCAU 5873 AUGCGGAG GCCGAAAGGCGAGUGAGGUCU GCGGCCUC 6150 789 CGCGCUCC G CAUGGAGC 5874 GCUCCAUG GCCGAAAGGCGAGUGAGGUCU GGAGCGCG 6151 796 CGCAUGGA G CGCCAGGC 5875 GCCUGGCG GCCGAAAGGCGAGUGAGGUCU UCCAUGCG 6152 798 CAUGGAGC G CCAGGCCG 5876 CGGCCUGG GCCGAAAGGCGAGUGAGGUCU GCUCCAUG 6153 803 AGCGCCAG G CCGCCUCG 5877 CGAGGCGG GCCGAAAGGCGAGUGAGGUCU CUGGCGCU 6154 806 GCCAGGCC G CCUCGGAG 5878 CUCCGAGG GCCGAAAGGCGAGUGAGGUCU GGCCUGGC 6155

826 AAGAGGAA G CUGGCCCA 5879 UGGGCCAG GCCGAAAGGCGAGUGAGGUCU UUCCUCUU 6156 830 GGAAGCUG G CCCAGUUG 5880 CAACUGGG GCCGAAAGGCGAGUGAGGUCU CAGCUUCC 6157 835 CUGGCCCA G UUGCAGGU 5881 ACCUGCAA GCCGAAAGGCGAGUGAGGUCU UGGGCCAG 6158 838 GCCCAGUU G CAGGUGGC 5882 GCCACCUG GCCGAAAGGCGAGUGAGGUCU AACUGGGC 6159 842 AGUUGCAG G UGGCCUAU 5883 AUAGGCCA GCCGAAAGGCGAGUGAGGUCU CUGCAACU 6160 845 UGCAGGUG G CCUAUCAC 5884 GUGAUAGG GCCGAAAGGCGAGUGAGGUCU CACCUGCA 6161 856 UAUCACCA G CUCUUCCA 5885 UGGAAGAG GCCGAAAGGCGAGUGAGGUCU UGGUGAUA 6162 888 CAUCAAGA G CAGCGUGG 5886 CCACGCUG GCCGAAAGGCGAGUGAGGUCU UCUUGAUG 6163 891 CAAGAGCA G CGUGGUGG 5887 CCACCACG GCCGAAAGGCGAGUGAGGUCU UGCUCUUG 6164 893 AGAGCAGC G UGGUGGGC 5888 GCCCACCA GCCGAAAGGCGAGUGAGGUCU GCUGCUCU 6165 896 GCAGCGUG G UGGGCAGU 5889 ACUGCCCA GCCGAAAGGCGAGUGAGGUCU CACGCUGC 6166 900 CGUGGUGG G CAGUGAGC 5890 GCUCACUG GCCGAAAGGCGAGUGAGGUCU CCACCACG 6167 903 GGUGGGCA G UGAGCGGA 5891 UCCGCUCA GCCGAAAGGCGAGUGAGGUCU UGCCCACC 6168 907 GGCAGUGA G CGGAAGCG 5892 CGCUUCCG GCCGAAAGGCGAGUGAGGUCU UCACUGCC 6169 913 GAGCGGAA G CGAGGAAU 5893 AUUCCUCG GCCGAAAGGCGAGUGAGGUCU UUCCGCUC 6170 922 CGAGGAAU G CAGCUGGA 5894 UCCAGCUG GCCGAAAGGCGAGUGAGGUCU AUUCCUCG 6171 925 GGAAUGCA G CUGGAAGA 5895 UCUUCCAG GCCGAAAGGCGAGUGAGGUCU UGCAUUCC 6172 943 CUCAAACA G CAGCUCCA 5896 UGGAGCUG GCCGAAAGGCGAGUGAGGUCU UGUUUGAG 6173 946 AAACAGCA G CUCCAGCA 5897 UGCUGGAG GCCGAAAGGCGAGUGAGGUCU UGCUGUUU 6174 952 CAGCUCCA G CAGGCCGA 5898 UCGGCCUG GCCGAAAGGCGAGUGAGGUCU UGGAGCUG 6175 956 UCCAGCAG G CCGAGGAG 5899 CUCCUCGG GCCGAAAGGCGAGUGAGGUCU CUGCUGGA 6176 965 CCGAGGAG G CCCUGGUG 5900 CACCAGGG GCCGAAAGGCGAGUGAGGUCU CUCCUCGG 6177 971 AGGCCCUG G UGGCCAAA 5901 UUUGGCCA GCCGAAAGGCGAGUGAGGUCU CAGGGCCU 6178 974 CCCUGGUG G CCAAACAG 5902 CUGUUUGG GCCGAAAGGCGAGUGAGGUCU CACCAGGG 6179 986 AACAGGAG G UGAUCGAU 5903 AUCGAUCA GCCGAAAGGCGAGUGAGGUCU CUCCUGUU 6180 997 AUCGAUAA G CUGAAGGA 5904 UCCUUCAG GCCGAAAGGCGAGUGAGGUCU UUAUCGAU 6181 1010 AGGAGGAG G CCGAGCAG 5905 CUGCUCGG GCCGAAAGGCGAGUGAGGUCU CUCCUCCU 6182 1015 GAGGCCGA G CAGCACAA 5906 UUGUGCUG GCCGAAAGGCGAGUGAGGUCU UCGGCCUC 6183 1018 GCCGAGCA G CACAAGAU 5907 AUCUUGUG GCCGAAAGGCGAGUGAGGUCU UGCUCGGC 6184 1028 ACAAGAUU G UGAUGGAG 5908 CUCCAUCA GCCGAAAGGCGAGUGAGGUCU AAUCUUGU 6185 1040 UGGAGACC G UUCCGGUG 5909 CACCGGAA GCCGAAAGGCGAGUGAGGUCU GGUCUCCA 6186 1046 CCGUUCCG G UGCUGAAG 5910 CUUCAGCA GCCGAAAGGCGAGUGAGGUCU CGGAACGG 6187 1048 GUUCCGGU G CUGAAGGC 5911 GCCUUCAG GCCGAAAGGCGAGUGAGGUCU ACCGGAAC 6188 1055 UGCUGAAG G CCCAGGCG 5912 CGCCUGGG GCCGAAAGGCGAGUGAGGUCU CUUCAGCA 6189 1061 AGGCCCAG G CGGAUAUC 5913 GAUAUCCG GCCGAAAGGCGAGUGAGGUCU CUGGGCCU 6190 1076 UCUACAAG G CGGACUUC 5914 GAAGUCCG GCCGAAAGGCGAGUGAGGUCU CUUGUAGA 6191 1088 ACUUCCAG G CUGAGAGG 5915 CCUCUCAG GCCGAAAGGCGAGUGAGGUCU CUGGAAGU 6192 1096 GCUGAGAG G CAGGCCCG 5916 CGGGCCUG GCCGAAAGGCGAGUGAGGUCU CUCUCAGC 6193 1100 AGAGGCAG G CCCGGGAG 5917 CUCCCGGG GCCGAAAGGCGAGUGAGGUCU CUGCCUCU 6194 1111 CGGGAGAA G CUGGCCGA 5918 UCGGCCAG GCCGAAAGGCGAGUGAGGUCU UUCUCCCG 6195 1115 AGAAGCUG G CCGAGAAG 5919 CUUCUCGG GCCGAAAGGCGAGUGAGGUCU CAGCUUCU 6196 1129 AAGAAGGA G CUCCUGCA 5920 UGCAGGAG GCCGAAAGGCGAGUGAGGUCU UCCUUCUU 6197 1135 GAGCUCCU G CAGGAGCA 5921 UGCUCCUG GCCGAAAGGCGAGUGAGGUCU AGGAGCUC 6198 1141 CUGCAGGA G CAGCUGGA 5922 UCCAGCUG GCCGAAAGGCGAGUGAGGUCU UCCUGCAG 6199 1144 CAGGAGCA G CUGGAGCA 5923 UGCUCCAG GCCGAAAGGCGAGUGAGGUCU UGCUCCUG 6200 1150 CAGCUGGA G CAGCUGCA 5924 UGCAGCUG GCCGAAAGGCGAGUGAGGUCU UCCAGCUG 6201 1153 CUGGAGCA G CUGCAGAG 5925 CUCUGCAG GCCGAAAGGCGAGUGAGGUCU UGCUCCAG 6202 1156 GAGCAGCU G CAGAGGGA 5926 UCCCUCUG GCCGAAAGGCGAGUGAGGUCU AGCUGCUC 6203 1165 CAGAGGGA G UACAGCAA 5927 UUGCUGUA GCCGAAAGGCGAGUGAGGUCU UCCCUCUG 6204 1170 GGAGUACA G CAAACUGA 5928 UCAGUUUG GCCGAAAGGCGAGUGAGGUCU UGUACUCC 6205 1181 AACUGAAG G CCAGCUGU 5929 ACAGCUGG GCCGAAAGGCGAGUGAGGUCU CUUCAGUU 6206 1185 GAAGGCCA G CUGUCAGG 5930 CCUGACAG GCCGAAAGGCGAGUGAGGUCU UGGCCUUC 6207 1188 GGCCAGCU G UCAGGAGU 5931 ACUCCUGA GCCGAAAGGCGAGUGAGGUCU AGCUGGCC 6208 1195 UGUCAGGA G UCGGCCAG 5932 CUGGCCGA GCCGAAAGGCGAGUGAGGUCU UCCUGACA 6209 1199 AGGAGUCG G CCAGGAUC 5933 GAUCCUGG GCCGAAAGGCGAGUGAGGUCU CGACUCCU 6210 1222 AUGAGGAA G CGGCAUGU 5934 ACAUGCCG GCCGAAAGGCGAGUGAGGUCU UUCCUCAU 6211 1225 AGGAAGCG G CAUGUCGA 5935 UCGACAUG GCCGAAAGGCGAGUGAGGUCU CGCUUCCU 6212 1229 AGCGGCAU G UCGAGGUC 5936 GACCUCGA GCCGAAAGGCGAGUGAGGUCU AUGCCGCU 6213 1235 AUGUCGAG G UCUCCCAG 5937 CUGGGAGA GCCGAAAGGCGAGUGAGGUCU CUCGACAU 6214 1244 UCUCCCAG G CCCCCUUG 5938 CAAGGGGG GCCGAAAGGCGAGUGAGGUCU CUGGGAGA 6215 1252 GCCCCCUU G CCCCCCGC 5939 GCGGGGGG GCCGAAAGGCGAGUGAGGUCU AAGGGGGC 6216 1259 UGCCCCCC G CCCCUGCC 5940 GGCAGGGG GCCGAAAGGCGAGUGAGGUCU GGGGGGCA 6217 1265 CCGCCCCU G CCUACCUC 5941 GAGGUAGG GCCGAAAGGCGAGUGAGGUCU AGGGGCGG 6218 1286 CUCCCCUG G CCCUGCCC 5942 GGGCAGGG GCCGAAAGGCGAGUGAGGUCU CAGGGGAG 6219 1291 CUGGCCCU G CCCAGCCA 5943 UGGCUGGG GCCGAAAGGCGAGUGAGGUCU AGGGCCAG 6220 1296 CCUGCCCA G CCAGAGGA 5944 UCCUCUGG GCCGAAAGGCGAGUGAGGUCU UGGGCAGG 6221 1308 GAGGAGGA G CCCCCCCG 5945 CGGGGGGG GCCGAAAGGCGAGUGAGGUCU UCCUCCUC 6222 1321 CCCGAGGA G CCACCUGA 5946 UCAGGUGG GCCGAAAGGCGAGUGAGGUCU UCCUCGGG 6223 1335 UGACUUCU G CUGUCCCA 5947 UGGGACAG GCCGAAAGGCGAGUGAGGUCU AGAAGUCA 6224 1338 CUUCUGCU G UCCCAAGU 5948 ACUUGGGA GCCGAAAGGCGAGUGAGGUCU AGCAGAAG 6225 1345 UGUCCCAA G UGCCAGUA 5949 UACUGGCA GCCGAAAGGCGAGUGAGGUCU UUGGGACA 6226 1347 UCCCAAGU G CCAGUAUC 5950 GAUACUGG GCCGAAAGGCGAGUGAGGUCU ACUUGGGA 6227 1351 AAGUGCCA G UAUCAGGC 5951 GCCUGAUA GCCGAAAGGCGAGUGAGGUCU UGGCACUU 6228 1358 AGUAUCAG G CCCCUGAU 5952 AUCAGGGG GCCGAAAGGCGAGUGAGGUCU CUGAUACU 6229 1378 GACACCCU G CAGAUACA 5953 UGUAUCUG GCCGAAAGGCGAGUGAGGUCU AGGGUGUC 6230 1388 AGAUACAU G UCAUGGAG 5954 CUCCAUGA GCCGAAAGGCGAGUGAGGUCU AUGUAUCU 6231 1396 GUCAUGGA G UGCAUUGA 5955 UCAAUGCA GCCGAAAGGCGAGUGAGGUCU UCCAUGAC 6232 1398 CAUGGAGU G CAUUGAGU 5956 ACUCAAUG GCCGAAAGGCGAGUGAGGUCU ACUCCAUG 6233 1405 UGCAUUGA G UAGGGCCG 5957 CGGCCCUA GCCGAAAGGCGAGUGAGGUCU UCAAUGCA 6234 1410 UGAGUAGG G CCGGCCAG 5958 CUGGCCGG GCCGAAAGGCGAGUGAGGUCU CCUACUCA 6235 1414 UAGGGCCG G CCAGUGCA 5959 UGCACUGG GCCGAAAGGCGAGUGAGGUCU CGGCCCUA 6236 1418 GCCGGCCA G UGCAAGGC 5960 GCCUUGCA GCCGAAAGGCGAGUGAGGUCU UGGCCGGC 6237 1420 CGGCCAGU G CAAGGCCA 5961 UGGCCUUG GCCGAAAGGCGAGUGAGGUCU ACUGGCCG 6238 1425 AGUGCAAG G CCACUGCC 5962 GGCAGUGG GCCGAAAGGCGAGUGAGGUCU CUUGCACU 6239 1431 AGGCCACU G CCUGCCCG 5963 CGGGCAGG GCCGAAAGGCGAGUGAGGUCU AGUGGCCU 6240 1435 CACUGCCU G CCCGAGGA 5964 UCCUCGGG GCCGAAAGGCGAGUGAGGUCU AGGCAGUG 6241 1445 CCGAGGAC G UGCCCGGG 5965 CCCGGGCA GCCGAAAGGCGAGUGAGGUCU GUCCUCGG 6242 1447 GAGGACGU G CCCGGGAC 5966 GUCCCGGG GCCGAAAGGCGAGUGAGGUCU ACGUCCUC 6243 1457 CCGGGACC G UGCAGUCU 5967 AGACUGCA GCCGAAAGGCGAGUGAGGUCU GGUCCCGG 6244 1459 GGGACCGU G CAGUCUGC 5968 GCAGACUG GCCGAAAGGCGAGUGAGGUCU ACGGUCCC 6245 1462 ACCGUGCA G UCUGCGCU 5969 AGCGCAGA GCCGAAAGGCGAGUGAGGUCU UGCACGGU 6246 1466 UGCAGUCU G CGCUUUCC 5970 GGAAAGCG GCCGAAAGGCGAGUGAGGUCU AGACUGCA 6247

1468 CAGUCUGC G CUUUCCUC 5971 GAGGAAAG GCCGAAAGGCGAGUGAGGUCU GCAGACUG 6248 1481 CCUCUCCC G CCUGCCUA 5972 UAGGCAGG GCCGAAAGGCGAGUGAGGUCU GGGAGAGG 6249 1485 UCCCGCCU G CCUAGCCC 5973 GGGCUAGG GCCGAAAGGCGAGUGAGGUCU AGGCGGGA 6250 1490 CCUGCCUA G CCCAGGAU 5974 AUCCUGGG GCCGAAAGGCGAGUGAGGUCU UAGGCAGG 6251 1504 GAUGAAGG G CUGGGUGG 5975 CCACCCAG GCCGAAAGGCGAGUGAGGUCU CCUUCAUC 6252 1509 AGGGCUGG G UGGCCACA 5976 UGUGGCCA GCCGAAAGGCGAGUGAGGUCU CCAGCCCU 6253 1512 GCUGGGUG G CCACAACU 5977 AGUUGUGG GCCGAAAGGCGAGUGAGGUCU CACCCAGC 6254 1526 ACUGGGAU G CCACCUGG 5978 CCAGGUGG GCCGAAAGGCGAGUGAGGUCU AUCCCAGU 6255 1536 CACCUGGA G CCCCACCC 5979 GGGUGGGG GCCGAAAGGCGAGUGAGGUCU UCCAGGUG 6256 1549 ACCCAGGA G CUGGCCGC 5980 GCGGCCAG GCCGAAAGGCGAGUGAGGUCU UCCUGGGU 6257 1553 AGGAGCUG G CCGCGGCA 5981 UGCCGCGG GCCGAAAGGCGAGUGAGGUCU CAGCUCCU 6258 1556 AGCUGGCC G CGGCACCU 5982 AGGUGCCG GCCGAAAGGCGAGUGAGGUCU GGCCAGCU 6259 1559 UGGCCGCG G CACCUUAC 5983 GUAAGGUG GCCGAAAGGCGAGUGAGGUCU CGCGGCCA 6260 1568 CACCUUAC G CUUCAGCU 5984 AGCUGAAG GCCGAAAGGCGAGUGAGGUCU GUAAGGUG 6261 1574 ACGCUUCA G CUGUUGAU 5985 AUCAACAG GCCGAAAGGCGAGUGAGGUCU UGAAGCGU 6262 1577 CUUCAGCU G UUGAUCCG 5986 CGGAUCAA GCCGAAAGGCGAGUGAGGUCU AGCUGAAG 6263 1585 GUUGAUCC G CUGGUCCC 5987 GGGACCAG GCCGAAAGGCGAGUGAGGUCU GGAUCAAC 6264 1589 AUCCGCUG G UCCCCUCU 5988 AGAGGGGA GCCGAAAGGCGAGUGAGGUCU CAGCGGAU 6265 1604 CUUUUGGG G UAGAUGCG 5989 CGCAUCUA GCCGAAAGGCGAGUGAGGUCU CCCAAAAG 6266 1610 GGGUAGAU G CGGCCCCG 5990 CGGGGCCG GCCGAAAGGCGAGUGAGGUCU AUCUACCC 6267 1613 UAGAUGCG G CCCCGAUC 5991 GAUCGGGG GCCGAAAGGCGAGUGAGGUCU CGCAUCUA 6268 1624 CCGAUCAG G CCUGACUC 5992 GAGUCAGG GCCGAAAGGCGAGUGAGGUCU CUGAUCGG 6269 1633 CCUGACUC G CUGCUCUU 5993 AAGAGCAG GCCGAAAGGCGAGUGAGGUCU GAGUCAGG 6270 1636 GACUCGCU G CUCUUUUU 5994 AAAAAGAG GCCGAAAGGCGAGUGAGGUCU AGCGAGUC 6271 1645 CUCUUUUU G UUCCCUUC 5995 GAAGGGAA GCCGAAAGGCGAGUGAGGUCU AAAAAGAG 6272 1655 UCCCUUCU G UCUGCUCG 5996 CGAGCAGA GCCGAAAGGCGAGUGAGGUCU AGAAGGGA 6273 1659 UUCUGUCU G CUCGAACC 5997 GGUUCGAG GCCGAAAGGCGAGUGAGGUCU AGACAGAA 6274 1672 AACCACUU G CCUCGGGC 5998 GCCCGAGG GCCGAAAGGCGAGUGAGGUCU AAGUGGUU 6275 1679 UGCCUCGG G CUAAUCCC 5999 GGGAUUAG GCCGAAAGGCGAGUGAGGUCU CCGAGGCA 6276 1706 UCCACCCG G CACUGGGG 6000 CCCCAGUG GCCGAAAGGCGAGUGAGGUCU CGGGUGGA 6277 1717 CUGGGGAA G UCAAGAAU 6001 AUUCUUGA GCCGAAAGGCGAGUGAGGUCU UUCCCCAG 6278 1729 AGAAUGGG G CCUGGGGC 6002 GCCCCAGG GCCGAAAGGCGAGUGAGGUCU CCCAUUCU 6279 1736 GGCCUGGG G CUCUCAGG 6003 CCUGAGAG GCCGAAAGGCGAGUGAGGUCU CCCAGGCC 6280 1752 GGAGAACU G CUUCCCCU 6004 AGGGGAAG GCCGAAAGGCGAGUGAGGUCU AGUUCUCC 6281 1762 UUCCCCUG G CAGAGCUG 6005 CAGCUCUG GCCGAAAGGCGAGUGAGGUCU CAGGGGAA 6282 1767 CUGGCAGA G CUGGGUGG 6006 CCACCCAG GCCGAAAGGCGAGUGAGGUCU UCUGCCAG 6283 1772 AGAGCUGG G UGGCAGCU 6007 AGCUGCCA GCCGAAAGGCGAGUGAGGUCU CCAGCUCU 6284 1775 GCUGGGUG G CAGCUCUU 6008 AAGAGCUG GCCGAAAGGCGAGUGAGGUCU CACCCAGC 6285 1778 GGGUGGCA G CUCUUCCU 6009 AGGAAGAG GCCGAAAGGCGAGUGAGGUCU UGCCACCC 6286 1805 ACCGACCC G CCCGCCGC 6010 GCGGCGGG GCCGAAAGGCGAGUGAGGUCU GGGUCGGU 6287 1809 ACCCGCCC G CCGCUGUG 6011 CACAGCGG GCCGAAAGGCGAGUGAGGUCU GGGCGGGU 6288 1812 CGCCCGCC G CUGUGCCC 6012 GGGCACAG GCCGAAAGGCGAGUGAGGUCU GGCGGGCG 6289 1815 CCGCCGCU G UGCCCUGG 6013 CCAGGGCA GCCGAAAGGCGAGUGAGGUCU AGCGGCGG 6290 1817 GCCGCUGU G CCCUGGGA 6014 UCCCAGGG GCCGAAAGGCGAGUGAGGUCU ACAGCGGC 6291 1826 CCCUGGGA G UGCUGCCC 6015 GGGCAGCA GCCGAAAGGCGAGUGAGGUCU UCCCAGGG 6292 1828 CUGGGAGU G CUGCCCUC 6016 GAGGGCAG GCCGAAAGGCGAGUGAGGUCU ACUCCCAG 6293 1831 GGAGUGCU G CCCUCUUA 6017 UAAGAGGG GCCGAAAGGCGAGUGAGGUCU AGCACUCC 6294 1844 CUUACCAU G CACACGGG 6018 CCCGUGUG GCCGAAAGGCGAGUGAGGUCU AUGGUAAG 6295 1852 GCACACGG G UGCUCUCC 6019 GGAGAGCA GCCGAAAGGCGAGUGAGGUCU CCGUGUGC 6296 1854 ACACGGGU G CUCUCCUU 6020 AAGGAGAG GCCGAAAGGCGAGUGAGGUCU ACCCGUGU 6297 1867 CCUUUUGG G CUGCAUGC 6021 GCAUGCAG GCCGAAAGGCGAGUGAGGUCU CCAAAAGG 6298 1870 UUUGGGCU G CAUGCUAU 6022 AUAGCAUG GCCGAAAGGCGAGUGAGGUCU AGCCCAAA 6299 1874 GGCUGCAU G CUAUUCCA 6023 UGGAAUAG GCCGAAAGGCGAGUGAGGUCU AUGCAGCC 6300 1887 UCCAUUUU G CAGCCAGA 6024 UCUGGCUG GCCGAAAGGCGAGUGAGGUCU AAAAUGGA 6301 1890 AUUUUGCA G CCAGACCG 6025 CGGUCUGG GCCGAAAGGCGAGUGAGGUCU UGCAAAAU 6302 1901 AGACCGAU G UGUAUUUA 6026 UAAAUACA GCCGAAAGGCGAGUGAGGUCU AUCGGUCU 6303 1903 ACCGAUGU G UAUUUAAC 6027 GUUAAAUA GCCGAAAGGCGAGUGAGGUCU ACAUCGGU 6304 1914 UUUAACCA G UCACUAUU 6028 AAUAGUGA GCCGAAAGGCGAGUGAGGUCU UGGUUAAA 6305 1936 ACAUUUGG G UUGUUUCC 6029 GGAAACAA GCCGAAAGGCGAGUGAGGUCU CCAAAUGU 6306 1939 UUUGGGUU G UUUCCCAU 6030 AUGGGAAA GCCGAAAGGCGAGUGAGGUCU AACCCAAA 6307 1954 AUCUUUUU G UUACCAUA 6031 UAUGGUAA GCCGAAAGGCGAGUGAGGUCU AAAAAGAU 6308 1970 AAAUAAUG G CAUAGUAA 6032 UUACUAUG GCCGAAAGGCGAGUGAGGUCU CAUUAUUU 6309 1975 AUGGCAUA G UAAAAAAA 6033 UUUUUUUA GCCGAAAGGCGAGUGAGGUCU UAUGCCAU 6310 Input Sequence = NM_003639. Cut Site = G/Y Arm Length = 8. Core Sequence = GCcgaaagGCGaGuCaaGGuCu NM_003639 (Homo sapiens inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase gamma (IKBKG), mRNA.; 1994 bp)

[0268] TABLE-US-00006 TABLE VI Human IKK-gamma DNAzyme and Substrate Sequence Seq Seq Pos Substrate ID DNAzyme ID 10 GCACGAGC A UGGCCCUU 4749 AAGGGCCA GGCTAGCTACAACGA GCTCGTGC 6380 13 CGAGCAUG G CCCUUGUG 5757 CACAAGGG GGCTAGCTACAACGA CATGCTCG 6381 19 UGGCCCUU G UGAUCCAG 5758 CTGGATCA GGCTAGCTACAACGA AAGGGCCA 6382 22 CCCUUGUG A UCCAGGUG 6311 CACCTGGA GGCTAGCTACAACGA CACAAGGG 6383 28 UGAUCCAG G UGGGGAAA 5759 TTTCCCCA GGCTAGCTACAACGA CTGGATCA 6384 36 GUGGGGAA A CUAAGGCC 6312 GGCCTTAG GGCTAGCTACAACGA TTCCCCAC 6385 42 AAACUAAG G CCCAGAGA 5760 TCTCTGGG GGCTAGCTACAACGA CTTAGTTT 6386 52 CCAGAGAA G UGAGGACC 5761 GGTCCTCA GGCTAGCTACAACGA TTCTCTGG 6387 58 AAGUGAGG A CCCCGCAG 6313 CTGCGGGG GGCTAGCTACAACGA CCTCACTT 6388 63 AGGACCCC G CAGACUAU 5762 ATAGTCTG GGCTAGCTACAACGA GGGGTCCT 6389 67 CCCCGCAG A CUAUCAAU 6314 ATTGATAG GGCTAGCTACAACGA CTGCGGGG 6390 70 CGCAGACU A UCAAUCCC 4364 GGGATTGA GGCTAGCTACAACGA AGTCTGCG 6391 74 GACUAUCA A UCCCAGUC 6315 GACTGGGA GGCTAGCTACAACGA TGATAGTC 6392 80 CAAUCCCA G UCUCUUCC 5763 GGAAGAGA GGCTAGCTACAACGA TGGGATTG 6393 93 UUCCCCUC A CUCCCUGU 4774 ACAGGGAG GGCTAGCTACAACGA GAGGGGAA 6394 100 CACUCCCU G UGAAGCUC 5764 GAGCTTCA GGCTAGCTACAACGA AGGGAGTG 6395 105 CCUGUGAA G CUCUCCAG 5765 CTGGAGAG GGCTAGCTACAACGA TTCACAGG 6396 113 GCUCUCCA G CAUCAUCG 5766 CGATGATG GGCTAGCTACAACGA TGGAGAGC 6397 115 UCUCCAGC A UCAUCGAG 4783 CTCGATGA GGCTAGCTACAACGA GCTGGAGA 6398 118 CCAGCAUC A UCGAGGUC 4784 GACCTCGA GGCTAGCTACAACGA GATGCTGG 6399 124 UCAUCGAG G UCCCAUCA 5767 TGATGGGA GGCTAGCTACAACGA CTCGATGA 6400 129 GAGGUCCC A UCAGCCCU 4787 AGGGCTGA GGCTAGCTACAACGA GGGACCTC 6401 133 UCCCAUCA G CCCUUGCC 5768 GGCAAGGG GGCTAGCTACAACGA TGATGGGA 6402 139 CAGCCCUU G CCCUGUUG 5769 CAACAGGG GGCTAGCTACAACGA AAGGGCTG 6403 144 CUUGCCCU G DUGGAUGA 5770 TCATCCAA GGCTAGCTACAACGA AGGGCAAG 6404 149 CCUGUUGG A UGAAUAGG 6316 CCTATTCA GGCTAGCTACAACGA CCAACAGG 6405 153 UUGGAUGA A UAGGCACC 6317 GGTGCCTA GGCTAGCTACAACGA TCATCCAA 6406 157 AUGAAUAG G CACCUCUG 5771 CAGAGGTG GGCTAGCTACAACGA CTATTCAT 6407 159 GAAUAGGC A CCUCUGGA 4795 TCCAGAGG GGCTAGCTACAACGA GCCTATTC 6408 171 CUGGAAGA G CCAACUGU 5772 ACAGTTGG GGCTAGCTACAACGA TCTTCCAG 6409 175 AAGAGCCA A CUGUGUGA 6318 TCACACAG GGCTAGCTACAACGA TGGCTCTT 6410 178 AGCCAACU G UGUGAGAU 5773 ATCTCACA GGCTAGCTACAACGA AGTTGGCT 6411 180 CCAACUGU G UGAGAUGG 5774 CCATCTCA GGCTAGCTACAACGA ACAGTTGG 6412 185 UGUGUGAG A UGGUGCAG 6319 CTGCACCA GGCTAGCTACAACGA CTCACACA 6413 188 GUGAGAUG G UGCAGCCC 5775 GGGCTGCA GGCTAGCTACAACGA CATCTCAC 6414 190 GAGAUGGU G CAGCCCAG 5776 CTGGGCTG GGCTAGCTACAACGA ACCATCTC 6415 193 AUGGUGCA G CCCAGUGG 5777 CCACTGGG GGCTAGCTACAACGA TGCACCAT 6416 198 GCAGCCCA G UGGUGGCC 5778 GGCCACCA GGCTAGCTACAACGA TGGGCTGC 6417 201 GCCCAGUG G UGGCCCGG 5779 CCGGGCCA GGCTAGCTACAACGA CACTGGGC 6418 204 CAGUGGUG G CCCGGCAG 5780 CTGCCGGG GGCTAGCTACAACGA CACCACTG 6419 209 GUGGCCCG G CAGCAGAU 5781 ATCTGCTG GGCTAGCTACAACGA CGGGCCAC 6420 212 GCCCGGCA G CAGAUCAG 5782 CTGATCTG GGCTAGCTACAACGA TGCCGGGC 6421 216 GGCAGCAG A UCAGGACG 6320 CGTCCTGA GGCTAGCTACAACGA CTGCTGCC 6422 222 AGAUCAGG A CGUACUGG 6321 CCAGTACG GGCTAGCTACAACGA CCTGATCT 6423 224 AUCAGGAC G UACUGGGC 5783 GCCCAGTA GGCTAGCTACAACGA GTCCTGAT 6424 226 CAGGACGU A CUGGGCGA 4384 TCGCCCAG GGCTAGCTACAACGA ACGTCCTG 6425 231 CGUACUGG G CGAAGAGU 5784 ACTCTTCG GGCTAGCTACAACGA CCAGTACG 6426 238 GGCGAAGA G UCUCCUCU 5785 AGAGGAGA GGCTAGCTACAACGA TCTTCGCC 6427 253 CUGGGGAA G CCAGCCAU 5786 ATGGCTGG GGCTAGCTACAACGA TTCCCCAG 6428 257 GGAAGCCA G CCAUGCUG 5787 CAGCATGG GGCTAGCTACAACGA TGGCTTCC 6429 260 AGCCAGCC A UGCUGCAC 4819 GTGCAGCA GGCTAGCTACAACGA GGCTGGCT 6430 262 CCAGCCAU G CUGCACCU 5788 AGGTGCAG GGCTAGCTACAACGA ATGGCTGG 6431 265 GCCAUGCU G CACCUGCC 5789 GGCAGGTG GGCTAGCTACAACGA AGCATGGC 6432 267 CAUGCUGC A CCUGCCUU 4821 AAGGCAGG GGCTAGCTACAACGA GCAGCATG 6433 271 CUGCACCU G CCUUCAGA 5790 TCTGAAGG GGCTAGCTACAACGA AGGTGCAG 6434 280 CCUUCAGA A CAGGGCGC 6322 GCGCCCTG GGCTAGCTACAACGA TCTGAAGG 6435 285 AGAACAGG G CGCUCCUG 5791 CAGGAGCG GGCTAGCTACAACGA CCTGTTCT 6436 287 AACAGGGC G CUCCUGAG 5792 CTCAGGAG GGCTAGCTACAACGA GCCCTGTT 6437 296 CUCCUGAG A CCCUCCAG 6323 CTGGAGGG GGCTAGCTACAACGA CTCAGGAG 6438 304 ACCCUCCA G CGCUGCCU 5793 AGGCAGCG GGCTAGCTACAACGA TGGAGGGT 6439 306 CCUCCAGC G CUGCCUGG 5794 CCAGGCAG GGCTAGCTACAACGA GCTGGAGG 6440 309 CCAGCGCU G CCUGGAGG 5795 CCTCCAGG GGCTAGCTACAACGA AGCGCTGG 6441 321 GGAGGAGA A UCAAGAGC 6324 GCTCTTGA GGCTAGCTACAACGA TCTCCTCC 6442 328 AAUCAAGA G CUCCGAGA 5796 TCTCGGAG GGCTAGCTACAACGA TCTTGATT 6443 336 GCUCCGAG A UGCCAUCC 6325 GGATGGCA GGCTAGCTACAACGA CTCGGAGC 6444 338 UCCGAGAU G CCAUCCGG 5797 CCGGATGG GGCTAGCTACAACGA ATCTCGGA 6445 341 GAGAUGCC A UCCGGCAG 4843 CTGCCGGA GGCTAGCTACAACGA GGCATCTC 6446 346 GCCAUCCG G CAGAGCAA 5798 TTGCTCTG GGCTAGCTACAACGA CGGATGGC 6447 351 CCGGCAGA G CAACCAGA 5799 TCTGGTTG GGCTAGCTACAACGA TCTGCCGG 6448 354 GCAGAGCA A CCAGAUUC 6326 GAATCTGG GGCTAGCTACAACGA TGCTCTGC 6449 359 GCAACCAG A UUCUGCGG 6327 CCGCAGAA GGCTAGCTACAACGA CTGGTTGC 6450 364 CAGAUUCU G CGGGAGCG 5800 CGCTCCCG GGCTAGCTACAACGA AGAATCTG 6451 370 CUGCGGGA G CGCUGCGA 5801 TCGCAGCG GGCTAGCTACAACGA TCCCGCAG 6452 372 GCGGGAGC G CUGCGAGG 5802 CCTCGCAG GGCTAGCTACAACGA GCTCCCGC 6453 375 GGAGCGCU G CGAGGAGC 5803 GCTCCTCG GGCTAGCTACAACGA AGCGCTCC 6454 382 UGCGAGGA G CUUCUGCA 5804 TGCAGAAG GGCTAGCTACAACGA TCCTCGCA 6455 388 GAGCUUCU G CAUUUCCA 5805 TGGAAATG GGCTAGCTACAACGA AGAAGCTC 6456 390 GCUUCUGC A UUUCCAAG 4853 CTTGGAAA GGCTAGCTACAACGA GCAGAAGC 6457 398 AUUUCCAA G CCAGCCAG 5806 CTGGCTGG GGCTAGCTACAACGA TTGGAAAT 6458 402 CCAAGCCA G CCAGAGGG 5807 CCCTCTGG GGCTAGCTACAACGA TGGCTTGG 6459 421 GAGAAGGA G UUCCUCAU 5808 ATGAGGAA GGCTAGCTACAACGA TCCTTCTC 6460 428 AGUUCCUC A UGUGCAAG 4862 CTTGCACA GGCTAGCTACAACGA GAGGAACT 6461 430 UUCCUCAU G UGCAAGUU 5809 AACTTGCA GGCTAGCTACAACGA ATGAGGAA 6462 432 CCUCAUGU G CAAGUUCC 5810 GGAACTTG GGCTAGCTACAACGA ACATGAGG 6463 436 AUGUGCAA G UUCCAGGA 5811 TCCTGGAA GGCTAGCTACAACGA TTGCACAT 6464 446 UCCAGGAG G CCAGGAAA 5812 TTTCCTGG GGCTAGCTACAACGA CTCCTGGA 6465 454 GCCAGGAA A CUGGUGGA 6328 TCCACCAG GGCTAGCTACAACGA TTCCTGGC 6466 458 GGAAACUG G UGGAGAGA 5813 TCTCTCCA GGCTAGCTACAACGA CAGTTTCC 6467 466 GUGGAGAG A CUCGGCCU 6329 AGGCCGAG GGCTAGCTACAACGA CTCTCCAC 6468 471 GAGACUCG G CCUGGAGA 5814 TCTCCAGG GGCTAGCTACAACGA CGAGTCTC 6469 481 CUGGAGAA G CUCGAUCU 5815 AGATCGAG GGCTAGCTACAACGA TTCTCCAG 6470 486 GAAGCUCG A UCUGAAGA 6330 TCTTCAGA GGCTAGCTACAACGA CGAGCTTC 6471 496 CUGAAGAG G CAGAAGGA 5816 TCCTTCTG GGCTAGCTACAACGA CTCTTCAG 6472 505 CAGAAGGA G CAGGCUCU 5817 AGAGCCTG GGCTAGCTACAACGA TCCTTCTG 6473 509 AGGAGCAG G CUCUGCGG 5818 CCGCAGAG GGCTAGCTACAACGA CTGCTCCT 6474 514 CAGGCUCU G CGGGAGGU 5819 ACCTCCCG GGCTAGCTACAACGA AGAGCCTG 6475 521 UGCGGGAG G UGGAGCAC 5820 GTGCTCCA GGCTAGCTACAACGA CTCCCGCA 6476 526 GAGGUGGA G CACCUGAA 5821 TTCAGGTG GGCTAGCTACAACGA TCCACCTC 6477 528 GGUGGAGC A CCUGAAGA 4878 TCTTCAGG GGCTAGCTACAACGA GCTCCACC 6478 538 CUGAAGAG A UGCCAGCA 6331 TGCTGGCA GGCTAGCTACAACGA CTCTTCAG 6479 540 GAAGAGAU G CCAGCAGC 5822 GCTGCTGG GGCTAGCTACAACGA ATCTCTTC 6480 544 AGAUGCCA G CAGCAGAU 5823 ATCTGCTG GGCTAGCTACAACGA TGGCATCT 6481 547 UGCCAGCA G CAGAUGGC 5824 GCCATCTG GGCTAGCTACAACGA TGCTGGCA 6482 551 AGCAGCAG A UGGCUGAG 6332 CTCAGCCA GGCTAGCTACAACGA CTGCTGCT 6483 554 AGCAGAUG G CUGAGGAC 5825 GTCCTCAG GGCTAGCTACAACGA CATCTGCT 6484 561 GGCUGAGG A CAAGGCCU 6333 AGGCCTTG GGCTAGCTACAACGA CCTCAGCC 6485 566 AGGACAAG G CCUCUGUG 5826 CACAGAGG GGCTAGCTACAACGA CTTGTCCT 6486 572 AGGCCUCU G UGAAAGCC 5827 GGCTTTCA GGCTAGCTACAACGA AGAGGCCT 6487 578 CUGUGAAA G CCCAGGUG 5828 CACCTGGG GGCTAGCTACAACGA TTTCACAG 6488 584 AAGCCCAG G UGACGUCC 5829 GGACGTCA GGCTAGCTACAACGA CTGGGCTT 6489 587 GCCAGGUG A CGUCCUUG 6334 CAAGGACG GGCTAGCTACAACGA CACCTGGG 6490 589 CAGGUGAC G UCCUUGCU 5830 AGCAAGGA GGCTAGCTACAACGA GTCACCTG 6491 595 ACGUCCUU G CUCGGGGA 5831 TCCCCGAG GGCTAGCTACAACGA AAGGACGT 6492 604 CUCGGGGA G CUGCAGGA 5832 TCCTGCAG GGCTAGCTACAACGA TCCCCGAG 6493 607 GGGGAGCU G CAGGAGAG 5833 CTCTCCTG GGCTAGCTACAACGA AGCTCCCC 6494 615 GCAGGAGA G CCAGAGUC 5834 GACTCTGG GGCTAGCTACAACGA TCTCCTGC 6495 621 GAGCCAGA G UCGCUUGG 5835 CCAAGCGA GGCTAGCTACAACGA TCTGGCTC 6496 624 CCAGAGUC G CUUGGAGG 5836 CCTCCAAG GGCTAGCTACAACGA GACTCTGG 6497 632 GCUUGGAG G CUGCCACU 5837 AGTGGCAG GGCTAGCTACAACGA CTCCAAGC 6498 635 UGGAGGCU G CCACUAAG 5838 CTTAGTGG GGCTAGCTACAACGA AGCCTCCA 6499 638 AGGCUGCC A CUAAGGAA 4903 TTCCTTAG GGCTAGCTACAACGA GGCAGCCT 6500 646 ACUAAGGA A UGCCAGGC 6335 GCCTGGCA GGCTAGCTACAACGA TCCTTAGT 6501

648 UAAGGAAU G CCAGGCUC 5839 GAGCCTGG GGCTAGCTACAACGA ATTCCTTA 6502 653 AAUGCCAG G CUCUGGAG 5840 CTCCAGAG GGCTAGCTACAACGA CTGGCATT 6503 663 UCUGGAGG G UCGGGCCC 5841 GGGCCCGA GGCTAGCTACAACGA CCTCCAGA 6504 668 AGGGUCGG G CCCGGGCG 5842 CGCCCGGG GGCTAGCTACAACGA CCGACCCT 6505 674 GGGCCCGG G CGGCCAGC 5843 GCTGGCCG GGCTAGCTACAACGA CCGGGCCC 6506 677 CCCGGGCG G CCAGCGAG 5844 CTCGCTGG GGCTAGCTACAACGA CGCCCGGG 6507 681 GGCGGCCA G CGAGCAGG 5845 CCTGCTCG GGCTAGCTACAACGA TGGCCGCC 6508 685 GCCAGCGA G CAGGCGCG 5846 CGCGCCTG GGCTAGCTACAACGA TCGCTGGC 6509 689 GCGAGCAG G CGCGGCAG 5847 CTGCCGCG GGCTAGCTACAACGA CTGCTCGC 6510 691 GAGCAGGC G CGGCAGCU 5848 AGCTGCCG GGCTAGCTACAACGA GCCTGCTC 6511 694 CAGGCGCG G CAGCUGGA 5849 TCCAGCTG GGCTAGCTACAACGA CGCGCCTG 6512 697 GCGCGGCA G CUGGAGAG 5850 CTCTCCAG GGCTAGCTACAACGA TGCCGCGC 6513 705 GCUGGAGA G UGAGCGCG 5851 CGCGCTCA GGCTAGCTACAACGA TCTCCAGC 6514 709 GAGAGUGA G CGCGAGGC 5852 GCCTCGCG GGCTAGCTACAACGA TCACTCTC 6515 711 GAGUGAGC G CGAGGCGC 5853 GCGCCTCG GGCTAGCTACAACGA GCTCACTC 6516 716 AGCGCGAG G CGCUGCAG 5854 CTGCAGCG GGCTAGCTACAACGA CTCGCGCT 6517 718 CGCGAGGC G CUGCAGCA 5855 TGCTGCAG GGCTAGCTACAACGA GCCTCGCG 6518 721 GAGGCGCU G CAGCAGCA 5856 TGCTGCTG GGCTAGCTACAACGA AGCGCCTC 6519 724 GCGCUGCA G CAGCAGCA 5857 TGCTGCTG GGCTAGCTACAACGA TGCAGCGC 6520 727 CUGCAGCA G CAGCACAG 5858 CTGTGCTG GGCTAGCTACAACGA TGCTGCAG 6521 730 CAGCAGCA G CACAGCGU 5859 ACGCTGTG GGCTAGCTACAACGA TGCTGCTG 6522 732 GCAGCAGC A CAGCGUGC 4920 GCACGCTG GGCTAGCTACAACGA GCTGCTGC 6523 735 GCAGCACA G CGUGCAGG 5860 CCTGCACG GGCTAGCTACAACGA TGTGCTGC 6524 737 AGCACAGC G UGCAGGUG 5861 CACCTGCA GGCTAGCTACAACGA GCTGTGCT 6525 739 CACAGCGU G CAGGUGGA 5862 TCCACCTG GGCTAGCTACAACGA ACGCTGTG 6526 743 GCGUGCAG G UGGACCAG 5863 CTGGTCCA GGCTAGCTACAACGA CTGCACGC 6527 747 GCAGGUGG A CCAGCUGC 6336 GCAGCTGG GGCTAGCTACAACGA CCACCTGC 6528 751 GUGGACCA G CUGCGCAU 5864 ATGCGCAG GGCTAGCTACAACGA TGGTCCAC 6529 754 GACCAGCU G CGCAUGCA 5865 TGCATGCG GGCTAGCTACAACGA AGCTGGTC 6530 756 CCAGCUGC G CAUGCAGG 5866 CCTGCATG GGCTAGCTACAACGA GCAGCTGG 6531 758 AGCUGCGC A UGCAGGGC 4926 GCCCTGCA GGCTAGCTACAACGA GCGCAGCT 6532 760 CUGCGCAU G CAGGGCCA 5867 TGGCCCTG GGCTAGCTACAACGA ATGCGCAG 6533 765 CAUGCAGG G CCAGAGCG 5868 CGCTCTGG GGCTAGCTACAACGA CCTGCATG 6534 771 GGGCCAGA G CGUGGAGG 5869 CCTCCACG GGCTAGCTACAACGA TCTGGCCC 6535 773 GCCAGAGC G UGGAGGCC 5870 GGCCTCCA GGCTAGCTACAACGA GCTCTGGC 6536 779 GCGUGGAG G CCGCGCUC 5871 GAGCGCGG GGCTAGCTACAACGA CTCCACGC 6537 782 UGGAGGCC G CGCUCCGC 5872 GCGGAGCG GGCTAGCTACAACGA GGCCTCCA 6538 784 GAGGCCGC G CUCCGCAU 5873 ATGCGGAG GGCTAGCTACAACGA GCGGCCTC 6539 789 CGCGCUCC G CAUGGAGC 5874 GCTCCATG GGCTAGCTACAACGA GGAGCGCG 6540 791 CGCUCCGC A UGGAGCGC 4933 GCGCTCCA GGCTAGCTACAACGA GCGGAGCG 6541 796 CGCAUGGA G CGCCAGGC 5875 GCCTGGCG GGCTAGCTACAACGA TCCATGCG 6542 798 CAUGGAGC G CCAGGCCG 5876 CGGCCTGG GGCTAGCTACAACGA GCTCCATG 6543 803 AGCGCCAG G CCGCCUCG 5877 CGAGGCGG GGCTAGCTACAACGA CTGGCGCT 6544 806 GCCAGGCC G CCUCGGAG 5878 CTCCGAGG GGCTAGCTACAACGA GGCCTGGC 6545 826 AAGAGGAA G CUGGCCCA 5879 TGGGCCAG GGCTAGCTACAACGA TTCCTCTT 6546 830 GGAAGCUG G CCCAGUUG 5880 CAACTGGG GGCTAGCTACAACGA CAGCTTCC 6547 835 CUGGCCCA G UUGCAGGU 5881 ACCTGCAA GGCTAGCTACAACGA TGGGCCAG 6548 838 GCCCAGUU G CAGGUGGC 5882 GCCACCTG GGCTAGCTACAACGA AACTGGGC 6549 842 AGUUGCAG G UGGCCUAU 5883 ATAGGCCA GGCTAGCTACAACGA CTGCAACT 6550 845 UGCAGGUG G CCUAUCAC 5884 GTGATAGG GGCTAGCTACAACGA CACCTGCA 6551 849 GGUGGCCU A UCACCAGC 4423 GCTGGTGA GGCTAGCTACAACGA AGGCCACC 6552 852 GGCCUAUC A CCAGCUCU 4946 AGAGCTGG GGCTAGCTACAACGA GATAGGCC 6553 856 UAUCACCA G CUCUUCCA 5885 TGGAAGAG GGCTAGCTACAACGA TGGTGATA 6554 868 UUCCAAGA A UACGACAA 6337 TTGTCGTA GGCTAGCTACAACGA TCTTGGAA 6555 870 CCAAGAAU A CGACAACC 4428 GGTTGTCG GGCTAGCTACAACGA ATTCTTGG 6556 873 AGAAUACG A CAACCACA 6338 TGTGGTTG GGCTAGCTACAACGA CGTATTCT 6557 876 AUACGACA A CCACAUCA 6339 TGATGTGG GGCTAGCTACAACGA TGTCGTAT 6558 879 CGACAACC A CAUCAAGA 4955 TCTTGATG GGCTAGCTACAACGA GGTTGTCG 6559 881 ACAACCAC A UCAAGAGC 4956 GCTCTTGA GGCTAGCTACAACGA GTGGTTGT 6560 888 CAUCAAGA G CAGCGUGG 5886 CCACGCTG GGCTAGCTACAACGA TCTTGATG 6561 891 CAAGAGCA G CGUGGUGG 5887 CCACCACG GGCTAGCTACAACGA TGCTCTTG 6562 893 AGAGCAGC G UGGUGGGC 5888 GCCCACCA GGCTAGCTACAACGA GCTGCTCT 6563 896 GCAGCGUG 0 UGGGCAGU 5889 ACTGCCCA GGCTAGCTACAACGA CACGCTGC 6564 900 CGUGGUGG G CAGUGAGC 5890 GCTCACTG GGCTAGCTACAACGA CCACCACG 6565 903 GGUGGGCA G UGAGCGGA 5891 TCCGCTCA GGCTAGCTACAACGA TGCCCACC 6566 907 GGCAGUGA G CGGAAGCG 5892 CGCTTCCG GGCTAGCTACAACGA TCACTGCC 6567 913 GAGCGGAA G CGAGGAAU 5893 ATTCCTCG GGCTAGCTACAACGA TTCCGCTC 6568 920 AGCGAGGA A UGCAGCUG 6340 CAGCTGCA GGCTAGCTACAACGA TCCTCGCT 6569 922 CGAGGAAU G CAGCUGGA 5894 TCCAGCTG GGCTAGCTACAACGA ATTCCTCG 6570 925 GGAAUGCA G CUGGAAGA 5895 TCTTCCAG GGCTAGCTACAACGA TGCATTCC 6571 933 GCUGGAAG A UCUCAAAC 6341 GTTTGAGA GGCTAGCTACAACGA CTTCCAGC 6572 940 GAUCUCAA A CAGCAGCU 6342 AGCTGCTG GGCTAGCTACAACGA TTGAGATC 6573 943 CUCAAACA G CAGCUCCA 5896 TGGAGCTG GGCTAGCTACAACGA TGTTTGAG 6574 946 AAACAGCA G CUCCAGCA 5897 TGCTGGAG GGCTAGCTACAACGA TGCTGTTT 6575 952 CAGCUCCA G CAGGCCGA 5898 TCGGCCTG GGCTAGCTACAACGA TGGAGCTG 6576 956 UCCAGCAG G CCGAGGAG 5899 CTCCTCGG GGCTAGCTACAACGA CTGCTGGA 6577 965 CCGAGGAG G CCCUGGUG 5900 CACCAGGG GGCTAGCTACAACGA CTCCTCGG 6578 971 AGGCCCUG G UGGCCAAA 5901 TTTGGCCA GGCTAGCTACAACGA CAGGGCCT 6579 974 CCCUGGUG G CCAAACAG 5902 CTGTTTGG GGCTAGCTACAACGA CACCAGGG 6580 979 GUGGCCAA A CAGGAGGU 6343 ACCTCCTG GGCTAGCTACAACGA TTGGCCAC 6581 986 AACAGGAG G UGAUCGAU 5903 ATCGATCA GGCTAGCTACAACGA CTCCTGTT 6582 989 AGGAGGUG A UCGAUAAG 6344 CTTATCGA GGCTAGCTACAACGA CACCTCCT 6583 993 GGUGAUCG A UAAGCUGA 6345 TCAGCTTA GGCTAGCTACAACGA CGATCACC 6584 997 AUCGAUAA G CUGAAGGA 5904 TCCTTCAG GGCTAGCTACAACGA TTATCGAT 6585 1010 AGGAGGAG G CCGAGCAG 5905 CTGCTCGG GGCTAGCTACAACGA CTCCTCCT 6586 1015 GAGGCCGA G CAGCACAA 5906 TTGTGCTG GGCTAGCTACAACGA TCGGCCTC 6587 1018 GCCGAGCA G CACAAGAU 5907 ATCTTGTG GGCTAGCTACAACGA TGCTCGGC 6588 1020 CGAGCAGC A CAAGAUUG 4980 CAATCTTG GGCTAGCTACAACGA GCTGCTCG 6589 1025 AGCACAAG A UUGUGAUG 6346 CATCACAA GGCTAGCTACAACGA CTTGTGCT 6590 1028 ACAAGAUU G UGAUGGAG 5908 CTCCATCA GGCTAGCTACAACGA AATCTTGT 6591 1031 AGAUUGUG A UGGAGACC 6347 GGTCTCCA GGCTAGCTACAACGA CACAATCT 6592 1037 UGAUGGAG A CCGUUCCG 6348 CGGAACGG GGCTAGCTACAACGA CTCCATCA 6593 1040 UGGAGACC G UUCCGGUG 5909 CACCGGAA GGCTAGCTACAACGA GGTCTCCA 6594 1046 CCGUUCCG G UGCUGAAG 5910 CTTCAGCA GGCTAGCTACAACGA CGGAACGG 6595 1048 GUUCCGGU G CUGAAGGC 5911 GCCTTCAG GGCTAGCTACAACGA ACCGGAAC 6596 1055 UGCUGAAG G CCCAGGCG 5912 CGCCTGGG GGCTAGCTACAACGA CTTCAGCA 6597 1061 AGGCCCAG G CGGAUAUC 5913 GATATCCG GGCTAGCTACAACGA CTGGGCCT 6598 1065 CCAGGCGG A UAUCUACA 6349 TGTAGATA GGCTAGCTACAACGA CCGCCTGG 6599 1067 AGGCGGAU A UCUACAAG 4438 CTTGTAGA GGCTAGCTACAACGA ATCCGCCT 6600 1071 GGAUAUCU A CAAGGCGG 4440 CCGCCTTG GGCTAGCTACAACGA AGATATCC 6601 1076 UCUACAAG G CGGACUUC 5914 GAAGTCCG GGCTAGCTACAACGA CTTGTAGA 6602 1080 CAAGGCGG A CUUCCAGG 6350 CCTGGAAG GGCTAGCTACAACGA CCGCCTTG 6603 1088 ACUUCCAG G CUGAGAGG 5915 CCTCTCAG GGCTAGCTACAACGA CTGGAAGT 6604 1096 GCUGAGAG G CAGGCCCG 5916 CGGGCCTG GGCTAGCTACAACGA CTCTCAGC 6605 1100 AGAGGCAG G CCCGGGAG 5917 CTCCCGGG GGCTAGCTACAACGA CTGCCTCT 6606 1111 CGGGAGAA G CUGGCCGA 5918 TCGGCCAG GGCTAGCTACAACGA TTCTCCCG 6607 1115 AGAAGCUG G CCGAGAAG 5919 CTTCTCGG GGCTAGCTACAACGA CAGCTTCT 6608 1129 AAGAAGGA G CUCCUGCA 5920 TGCAGGAG GGCTAGCTACAACGA TCCTTCTT 6609 1135 GAGCUCCU G CAGGAGCA 5921 TGCTCCTG GGCTAGCTACAACGA AGGAGCTC 6610 1141 CUGCAGGA G CAGCUGGA 5922 TCCAGCTG GGCTAGCTACAACGA TCCTGCAG 6611 1144 CAGGAGCA G CUGGAGCA 5923 TGCTCCAG GGCTAGCTACAACGA TGCTCCTG 6612 1150 CAGCUGGA G CAGCUGCA 5924 TGCAGCTG GGCTAGCTACAACGA TCCAGCTG 6613 1153 CUGGAGCA G CUGCAGAG 5925 CTCTGCAG GGCTAGCTACAACGA TGCTCCAG 6614 1156 GAGCAGCU G CAGAGGGA 5926 TCCCTCTG GGCTAGCTACAACGA AGCTGCTC 6615 1165 CAGAGGGA G UACAGCAA 5927 TTGCTGTA GGCTAGCTACAACGA TCCCTCTG 6616 1167 GAGGGAGU A CAGCAAAC 4444 GTTTGCTG GGCTAGCTACAACGA ACTCCCTC 6617 1170 GGAGUACA G CAAACUGA 5928 TCAGTTTG GGCTAGCTACAACGA TGTACTCC 6618 1174 UACAGCAA A CUGAAGGC 6351 GCCTTCAG GGCTAGCTACAACGA TTGCTGTA 6619 1181 AACUGAAG G CCAGCUGU 5929 ACAGCTGG GGCTAGCTACAACGA CTTCAGTT 6620 1185 GAAGGCCA G CUGUCAGG 5930 CCTGACAG GGCTAGCTACAACGA TGGCCTTC 6621 1188 GGCCAGCU G UCAGGAGU 5931 ACTCCTGA GGCTAGCTACAACGA AGCTGGCC 6622 1195 UGUCAGGA G UCGGCCAG 5932 CTGGCCGA GGCTAGCTACAACGA TCCTGACA 6623 1199 AGGAGUCG G CCAGGAUC 5933 GATCCTGG GGCTAGCTACAACGA CGACTCCT 6624 1205 CGGCCAGG A UCGAGGAC 6352 GTCCTCGA GGCTAGCTACAACGA CCTGGCCG 6625 1212 GAUCGAGG A CAUGAGGA 6353 TCCTCATG GGCTAGCTACAACGA CCTCGATC 6626

1214 UCGAGGAC A UGAGGAAG 5017 CTTCCTCA GGCTAGCTACAACGA GTCCTCGA 6627 1222 AUGAGGAA G CGGCAUGU 5934 ACATGCCG GGCTAGCTACAACGA TTCCTCAT 6628 1225 AGGAAGCG G CAUGUCGA 5935 TCGACATG GGCTAGCTACAACGA CGCTTCCT 6629 1227 GAAGCGGC A UGUCGAGG 5018 CCTCGACA GGCTAGCTACAACGA GCCGCTTC 6630 1229 AGCGGCAU G UCGAGGUC 5936 GACCTCGA GGCTAGCTACAACGA ATGCCGCT 6631 1235 AUGUCGAG G UCUCCCAG 5937 CTGGGAGA GGCTAGCTACAACGA CTCGACAT 6632 1244 UCUCCCAG G CCCCCUUG 5938 CAAGGGGG GGCTAGCTACAACGA CTGGGAGA 6633 1252 GCCCCCUU G CCCCCCGC 5939 GCGGGGGG GGCTAGCTACAACGA AAGGGGGC 6634 1259 UGCCCCCC G CCCCUGCC 5940 GGCAGGGG GGCTAGCTACAACGA GGGGGGCA 6635 1265 CCGCCCCU G CCUACCUC 5941 GAGGTAGG GGCTAGCTACAACGA AGGGGCGG 6636 1269 CCCUGCCU A CCUCUCCU 4452 AGGAGAGG GGCTAGCTACAACGA AGGCAGGG 6637 1286 CUCCCCUG G CCCUGCCC 5942 GGGCAGGG GGCTAGCTACAACGA CAGGGGAG 6638 1291 CUGGCCCU G CCCAGCCA 5943 TGGCTGGG GGCTAGCTACAACGA AGGGCCAG 6639 1296 CCUGCCCA G CCAGAGGA 5944 TCCTCTGG GGCTAGCTACAACGA TGGGCAGG 6640 1308 GAGGAGGA G CCCCCCCG 5945 CGGGGGGG GGCTAGCTACAACGA TCCTCCTC 6641 1321 CCCGAGGA G CCACCUGA 5946 TCAGGTGG GGCTAGCTACAACGA TCCTCGGG 6642 1324 GAGGAGCC A CCUGACUU 5064 AAGTCAGG GGCTAGCTACAACGA GGCTCCTC 6643 1329 GCCACCUG A CUUCUGCU 6354 AGCAGAAG GGCTAGCTACAACGA CAGGTGGC 6644 1335 UGACUUCU G CUGUCCCA 5947 TGGGACAG GGCTAGCTACAACGA AGAAGTCA 6645 1338 CUUCUGCU G UCCCAAGU 5948 ACTTGGGA GGCTAGCTACAACGA AGCAGAAG 6646 1345 UGUCCCAA G UGCCAGUA 5949 TACTGGCA GGCTAGCTACAACGA TTGGGACA 6647 1347 UCCCAAGU G CCAGUAUC 5950 GATACTGG GGCTAGCTACAACGA ACTTGGGA 6648 1351 AAGUGCCA G UAUCAGGC 5951 GCCTGATA GGCTAGCTACAACGA TGGCACTT 6649 1353 GUGCCAGU A UCAGGCCC 4460 GGGCCTGA GGCTAGCTACAACGA ACTGGCAC 6650 1358 AGUAUCAG G CCCCUGAU 5952 ATCAGGGG GGCTAGCTACAACGA CTGATACT 6651 1365 GGCCCCUG A UAUGGACA 6355 TGTCCATA GGCTAGCTACAACGA CAGGGGCC 6652 1367 CCCCUGAU A UGGACACC 4462 GGTGTCCA GGCTAGCTACAACGA ATCAGGGG 6653 1371 UGAUAUGG A CACCCUGC 6356 GCAGGGTG GGCTAGCTACAACGA CCATATCA 6654 1373 AUAUGGAC A CCCUGCAG 5080 CTGCAGGG GGCTAGCTACAACGA GTCCATAT 6655 1378 GACACCCU G CAGAUACA 5953 TGTATCTG GGCTAGCTACAACGA AGGGTGTC 6656 1382 CCCUGCAG A UACAUGUC 6357 GACATGTA GGCTAGCTACAACGA CTGCAGGG 6657 1384 CUGCAGAU A CAUGUCAU 4463 ATGACATG GGCTAGCTACAACGA ATCTGCAG 6658 1386 GCAGAUAC A UGUCAUGG 5085 CCATGACA GGCTAGCTACAACGA GTATCTGC 6659 1388 AGAUACAU G UCAUGGAG 5954 CTCCATGA GGCTAGCTACAACGA ATGTATCT 6660 1391 UACAUGUC A UGGAGUGC 5086 GCACTCCA GGCTAGCTACAACGA GACATGTA 6661 1396 GUCAUGGA G UGCAUUGA 5955 TCAATGCA GGCTAGCTACAACGA TCCATGAC 6662 1398 CAUGGAGU G CAUUGAGU 5956 ACTCAATG GGCTAGCTACAACGA ACTCCATG 6663 1400 UGGAGUGC A UUGAGUAG 5087 CTACTCAA GGCTAGCTACAACGA GCACTCCA 6664 1405 UGCAUUGA G UAGGGCCG 5957 CGGCCCTA GGCTAGCTACAACGA TCAATGCA 6665 1410 UGAGUAGG G CCGGCCAG 5958 CTGGCCGG GGCTAGCTACAACGA CCTACTCA 6666 1414 UAGGGCCG G CCAGUGCA 5959 TGCACTGG GGCTAGCTACAACGA CGGCCCTA 6667 1418 GCCGGCCA G UGCAAGGC 5960 GCCTTGCA GGCTAGCTACAACGA TGGCCGGC 6668 1420 CGGCCAGU G CAAGGCCA 5961 TGGCCTTG GGCTAGCTACAACGA ACTGGCCG 6669 1425 AGUGCAAG G CCACUGCC 5962 GGCAGTGG GGCTAGCTACAACGA CTTGCACT 6670 1428 GCAAGGCC A CUGCCUGC 5093 GCAGGCAG GGCTAGCTACAACGA GGCCTTGC 6671 1431 AGGCCACU G CCUGCCCG 5963 CGGGCAGG GGCTAGCTACAACGA AGTGGCCT 6672 1435 CACUGCCU G CCCGAGGA 5964 TCCTCGGG GGCTAGCTACAACGA AGGCAGTG 6673 1443 GCCCGAGG A CGUGCCCG 6358 CGGGCACG GGCTAGCTACAACGA CCTCGGGC 6674 1445 CCGAGGAC G UGCCCGGG 5965 CCCGGGCA GGCTAGCTACAACGA GTCCTCGG 6675 1447 GAGGACGU G CCCGGGAC 5966 GTCCCGGG GGCTAGCTACAACGA ACGTCCTC 6676 1454 UGCCCGGG A CCGUGCAG 6359 CTGCACGG GGCTAGCTACAACGA CCCGGGCA 6677 1457 CCGGGACC G UGCAGUCU 5967 AGACTGCA GGCTAGCTACAACGA GGTCCCGG 6678 1459 GGGACCGU G CAGUCUGC 5968 GCAGACTG GGCTAGCTACAACGA ACGGTCCC 6679 1462 ACCGUGCA G UCUGCGCU 5969 AGCGCAGA GGCTAGCTACAACGA TGCACGGT 6680 1466 UGCAGUCU G CGCUUUCC 5970 GGAAAGCG GGCTAGCTACAACGA AGACTGCA 6681 1468 CAGUCUGC G CUUUCCUC 5971 GAGGAAAG GGCTAGCTACAACGA GCAGACTG 6682 1481 CCUCUCCC G CCUGCCUA 5972 TAGGCAGG GGCTAGCTACAACGA GGGAGAGG 6683 1485 UCCCGCCU G CCUAGCCC 5973 GGGCTAGG GGCTAGCTACAACGA AGGCGGGA 6684 1490 CCUGCCUA G CCCAGGAU 5974 ATCCTGGG GGCTAGCTACAACGA TAGGCAGG 6685 1497 AGCCCAGG A UGAAGGGC 6360 GCCCTTCA GGCTAGCTACAACGA CCTGGGCT 6686 1504 GAUGAAGG G CUGGGUGG 5975 CCACCCAG GGCTAGCTACAACGA CCTTCATC 6687 1509 AGGGCUGG G UGGCCACA 5976 TGTGGCCA GGCTAGCTACAACGA CCAGCCCT 6688 1512 GCUGGGUG G CCACAACU 5977 AGTTGTGG GGCTAGCTACAACGA CACCCAGC 6689 1515 GGGUGGCC A CAACUGGG 5119 CCCAGTTG GGCTAGCTACAACGA GGCCACCC 6690 1518 UGGCCACA A CUGGGAUG 6361 CATCCCAG GGCTAGCTACAACGA TGTGGCCA 6691 1524 CAACUGGG A UGCCACCU 6362 AGGTGGCA GGCTAGCTACAACGA CCCAGTTG 6692 1526 ACUGGGAU G CCACCUGG 5978 CCAGGTGG GGCTAGCTACAACGA ATCCCAGT 6693 1529 GGGAUGCC A CCUGGAGC 5123 GCTCCAGG GGCTAGCTACAACGA GGCATCCC 6694 1536 CACCUGGA G CCCCACCC 5979 GGGTGGGG GGCTAGCTACAACGA TCCAGGTG 6695 1541 GGAGCCCC A CCCAGGAG 5129 CTCCTGGG GGCTAGCTACAACGA GGGGCTCC 6696 1549 ACCCAGGA G CUGGCCGC 5980 GCGGCCAG GGCTAGCTACAACGA TCCTGGGT 6697 1553 AGGAGCUG G CCGCGGCA 5981 TGCCGCGG GGCTAGCTACAACGA CAGCTCCT 6698 1556 AGCUGGCC G CGGCACCU 5982 AGGTGCCG GGCTAGCTACAACGA GGCCAGCT 6699 1559 UGGCCGCG G CACCUUAC 5983 GTAAGGTG GGCTAGCTACAACGA CGCGGCCA 6700 1561 GCCGCGGC A CCUUACGC 5135 GCGTAAGG GGCTAGCTACAACGA GCCGCGGC 6701 1566 GGCACCUU A CGCUUCAG 4475 CTGAAGCG GGCTAGCTACAACGA AAGGTGCC 6702 1568 CACCUUAC G CUUCAGCU 5984 AGCTGAAG GGCTAGCTACAACGA GTAAGGTG 6703 1574 ACGCUUCA G CUGUUGAU 5985 ATCAACAG GGCTAGCTACAACGA TGAAGCGT 6704 1577 CUUCAGCU G UUGAUCCG 5986 CGGATCAA GGCTAGCTACAACGA AGCTGAAG 6705 1581 AGCUGUUG A UCCGCUGG 6363 CCAGCGGA GGCTAGCTACAACGA CAACAGCT 6706 1585 GUUGAUCC G CUGGUCCC 5987 GGGACCAG GGCTAGCTACAACGA GGATCAAC 6707 1589 AUCCGCUG G UCCCCUCU 5988 AGAGGGGA GGCTAGCTACAACGA CAGCGGAT 6708 1604 CUUUUGGG G UAGAUGCG 5989 CGCATCTA GGCTAGCTACAACGA CCCAAAAG 6709 1608 UGGGGUAG A UGCGGCCC 6364 GGGCCGCA GGCTAGCTACAACGA CTACCCCA 6710 1610 GGGUAGAU G CGGCCCCG 5990 CGGGGCCG GGCTAGCTACAACGA ATCTACCC 6711 1613 UAGAUGCG G CCCCGAUC 5991 GATCGGGG GGCTAGCTACAACGA CGCATCTA 6712 1619 CGGCCCCG A UCAGGCCU 6365 AGGCCTGA GGCTAGCTACAACGA CGGGGCCG 6713 1624 CCGAUCAG G CCUGACUC 5992 GAGTCAGG GGCTAGCTACAACGA CTGATCGG 6714 1629 CAGGCCUG A CUCGCUGC 6366 GCAGCGAG GGCTAGCTACAACGA CAGGCCTG 6715 1633 CCUGACUC G CUGCUCUU 5993 AAGAGCAG GGCTAGCTACAACGA GAGTCAGG 6716 1636 GACUCGCU G CUCUUUUU 5994 AAAAAGAG GGCTAGCTACAACGA AGCGAGTC 6717 1645 CUCUUUUU G UUCCCUUC 5995 GAAGGGAA GGCTAGCTACAACGA AAAAAGAG 6718 1655 UCCCUUCU G UCUGCUCG 5996 CGAGCAGA GGCTAGCTACAACGA AGAAGGGA 6719 1659 UUCUGUCU G CUCGAACC 5997 GGTTCGAG GGCTAGCTACAACGA AGACAGAA 6720 1665 CUGCUCGA A CCACUUGC 6367 GCAAGTGG GGCTAGCTACAACGA TCGAGCAG 6721 1668 CUCGAACC A CUUGCCUC 5165 GAGGCAAG GGCTAGCTACAACGA GGTTCGAG 6722 1672 AACCACUU G CCUCGGGC 5998 GCCCGAGG GGCTAGCTACAACGA AAGTGGTT 6723 1679 UGCCUCGG G CUAAUCCC 5999 GGGATTAG GGCTAGCTACAACGA CCGAGGCA 6724 1683 UCGGGCUA A UCCCUCCC 6368 GGGAGGGA GGCTAGCTACAACGA TAGCCCGA 6725 1701 CUUCCUCC A CCCGGCAC 5180 GTGCCGGG GGCTAGCTACAACGA GGAGGAAG 6726 1706 UCCACCCG G CACUGGGG 6000 CCCCAGTG GGCTAGCTACAACGA CGGGTGGA 6727 1708 CACCCGGC A CUGGGGAA 5183 TTCCCCAG GGCTAGCTACAACGA GCCGGGTG 6728 1717 CUGGGGAA G UCAAGAAU 6001 ATTCTTGA GGCTAGCTACAACGA TTCCCCAG 6729 1724 AGUCAAGA A UGGGGCCU 6369 AGGCCCCA GGCTAGCTACAACGA TCTTGACT 6730 1729 AGAAUGGG G CCUGGGGC 6002 GCCCCAGG GGCTAGCTACAACGA CCCATTCT 6731 1736 GGCCUGGG G CUCUCAGG 6003 CCTGAGAG GGCTAGCTACAACGA CCCAGGCC 6732 1749 CAGGGAGA A CUGCUUCC 6370 GGAAGCAG GGCTAGCTACAACGA TCTCCCTG 6733 1752 GGAGAACU G CUUCCCCU 6004 AGGGGAAG GGCTAGCTACAACGA AGTTCTCC 6734 1762 UUCCCCUG G CAGAGCUG 6005 CAGCTCTG GGCTAGCTACAACGA CAGGGGAA 6735 1767 CUGGCAGA G CUGGGUGG 6006 CCACCCAG GGCTAGCTACAACGA TCTGCCAG 6736 1772 AGAGCUGG G UGGCAGCU 6007 AGCTGCCA GGCTAGCTACAACGA CCAGCTCT 6737 1775 GCUGGGUG G CAGCUCUU 6008 AAGAGCTG GGCTAGCTACAACGA CACCCAGC 6738 1778 GGGUGGCA G CUCUUCCU 6009 AGGAAGAG GGCTAGCTACAACGA TGCCACCC 6739 1790 UUCCUCCC A CCGGACAC 5206 GTGTCCGG GGCTAGCTACAACGA GGGAGGAA 6740 1795 CCCACCGG A CACCGACC 6371 GGTCGGTG GGCTAGCTACAACGA CCGGTGGG 6741 1797 CACCGGAC A CCGACCCG 5208 CGGGTCGG GGCTAGCTACAACGA GTCCGGTG 6742 1801 GGACACCG A CCCGCCCG 6372 CGGGCGGG GGCTAGCTACAACGA CGGTGTCC 6743 1805 ACCGACCC G CCCGCCGC 6010 GCGGCGGG GGCTAGCTACAACGA GGGTCGGT 6744 1809 ACCCGCCC G CCGCUGUG 6011 CACAGCGG GGCTAGCTACAACGA GGGCGGGT 6745 1812 CGCCCGCC G CUGUGCCC 6012 GGGCACAG GGCTAGCTACAACGA GGCGGGCG 6746 1815 CCGCCGCU G UGCCCUGG 6013 CCAGGGCA GGCTAGCTACAACGA AGCGGCGG 6747 1817 GCCGCUGU G CCCUGGGA 6014 TCCCAGGG GGCTAGCTACAACGA ACAGCGGC 6748 1826 CCCUGGGA G UGCUGCCC 6015 GGGCAGCA GGCTAGCTACAACGA TCCCAGGG 6749 1828 CUGGGAGU G CUGCCCUC 6016 GAGGGCAG GGCTAGCTACAACGA ACTCCCAG 6750 1831 GGAGUGCU G CCCUCUUA 6017 TAAGAGGG GGCTAGCTACAACGA AGCACTCC 6751 1839 GCCCUCUU A CCAUGCAC 4519 GTGCATGG GGCTAGCTACAACGA AAGAGGGC 6752

1842 CUCUUACC A UGCACACG 5225 CGTGTGCA GGCTAGCTACAACGA GGTAAGAG 6753 1844 CUUACCAU G CACACGGG 6018 CCCGTGTG GGCTAGCTACAACGA ATGGTAAG 6754 1846 UACCAUGC A CACGGGUG 5226 CACCCGTG GGCTAGCTACAACGA GCATGGTA 6755 1848 CCAUGCAC A CGGGUGCU 5227 AGCACCCG GGCTAGCTACAACGA GTGCATGG 6756 1852 GCACACGG G UGCUCUCC 6019 GGAGAGCA GGCTAGCTACAACGA CCGTGTGC 6757 1854 ACACGGGU G CUCUCCUU 6020 AAGGAGAG GGCTAGCTACAACGA ACCCGTGT 6758 1867 CCUUUUGG G CUGCAUGC 6021 GCATGCAG GGCTAGCTACAACGA CCAAAAGG 6759 1870 UUUGGGCU G CAUGCUAU 6022 ATAGCATG GGCTAGCTACAACGA AGCCCAAA 6760 1872 UGGGCUGC A UGCUAUUC 5233 GAATAGCA GGCTAGCTACAACGA GCAGCCCA 6761 1874 GGCUGCAU G CUAUUCCA 6023 TGGAATAG GGCTAGCTACAACGA ATGCAGCC 6762 1877 UGCAUGCU A UUCCAUUU 4525 AAATGGAA GGCTAGCTACAACGA AGCATGCA 6763 1882 GCUAUUCC A UUUUGCAG 5236 CTGCAAAA GGCTAGCTACAACGA GGAATAGC 6764 1887 UCCAUUUU G CAGCCAGA 6024 TCTGGCTG GGCTAGCTACAACGA AAAATGGA 6765 1890 AUUUUGCA G CCAGACCG 6025 CGGTCTGG GGCTAGCTACAACGA TGCAAAAT 6766 1895 GCAGCCAG A CCGAUGUG 6373 CACATCGG GGCTAGCTACAACGA CTGGCTGC 6767 1899 CCAGACCG A UGUGUAUU 6374 AATACACA GGCTAGCTACAACGA CGGTCTGG 6768 1901 AGACCGAU G UGUAUUUA 6026 TAAATACA GGCTAGCTACAACGA ATCGGTCT 6769 1903 ACCGAUGU G UAUUUAAC 6027 GTTAAATA GGCTAGCTACAACGA ACATCGGT 6770 1905 CGAUGUGU A UUUAACCA 4531 TGGTTAAA GGCTAGCTACAACGA ACACATCG 6771 1910 UGUAUUUA A CCAGUCAC 6375 GTGACTGG GGCTAGCTACAACGA TAAATACA 6772 1914 UUUAACCA G UCACUAUU 6028 AATAGTGA GGCTAGCTACAACGA TGGTTAAA 6773 1917 AACCAGUC A CUAUUGAU 5243 ATCAATAG GGCTAGCTACAACGA GACTGGTT 6774 1920 CAGUCACU A UUGAUGGA 4536 TCCATCAA GGCTAGCTACAACGA AGTGACTG 6775 1924 CACUAUUG A UGGACAUU 6376 AATGTCCA GGCTAGCTACAACGA CAATAGTG 6776 1928 AUUGAUGG A CAUUUGGG 6377 CCCAAATG GGCTAGCTACAACGA CCATCAAT 6777 1930 UGAUGGAC A UUUGGGUU 5245 AACCCAAA GGCTAGCTACAACGA GTCCATCA 6778 1936 ACAUUUGG G UUGUUUCC 6029 GGAAACAA GGCTAGCTACAACGA CCAAATGT 6779 1939 UUUGGGUU G UUUCCCAU 6030 ATGGGAAA GGCTAGCTACAACGA AACCCAAA 6780 1946 UGUUUCCC A UCUUUUUG 5248 CAAAAAGA GGCTAGCTACAACGA GGGAAACA 6781 1954 AUCUUUUU G UUACCAUA 6031 TATGGTAA GGCTAGCTACAACGA AAAAAGAT 6782 1957 UUUUUGUU A CCAUAAAU 4550 ATTTATGG GGCTAGCTACAACGA AACAAAAA 6783 1960 UUGUUACC A UAAAUAAU 5251 ATTATTTA GGCTAGCTACAACGA GGTAACAA 6784 1964 UACCAUAA A UAAUGGCA 6378 TGCCATTA GGCTAGCTACAACGA TTATGGTA 6785 1967 CAUAAAUA A UGGCAUAG 6379 CTATGCCA GGCTAGCTACAACGA TATTTATG 6786 1970 AAAUAAUG G CAUAGUAA 6032 TTACTATG GGCTAGCTACAACGA CATTATTT 6787 1972 AUAAUGGC A UAGUAAAA 5252 TTTTACTA GGCTAGCTACAACGA GCCATTAT 6788 1975 AUGGCAUA G UAAAAAAA 6033 TTTTTTTA GGCTAGCTACAACGA TATGCCAT 6789 Input Sequence = NM_003639. Cut Site = R/Y Arm Length = 8. Core Sequence = GGCTAGCTACAACGA NM_003639 (Homo sapiens inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase gamma (IKBKG), mRNA.; 1994 bp)

[0269] TABLE-US-00007 TABLE VII Human IKK-gamma Amberzyme and Substrate Sequence Seq Seq Pos Substrate ID Amberzyme ID 12 ACGAGCAU G GCCCUUGU 6790 ACAAGGGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUGCUCGU 7142 13 CGAGCAUG G CCCUUGUG 5757 CACAAGGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAUGCUCG 7143 19 UGGCCCUU G UGAUCCAG 5758 CUGGAUCA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAGGGCCA 7144 21 GCCCUUGU G AUCCAGGU 6791 ACCUGGAU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACAAGGGC 7145 27 GUGAUCCA G GUGGGGAA 6792 UUCCCCAC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGGAUCAC 7146 28 UGAUCCAG G UGGGGAAA 5759 UUUCCCCA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUGGAUCA 7147 30 AUCCAGGU G GGGAAACU 6793 AGUUUCCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACCUGGAU 7148 31 UCCAGGUG G GGAAACUA 6794 UAGUUUCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CACCUGGA 7149 32 CCAGGUGG G GAAACUAA 6795 UUAGUUUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCACCUGG 7150 33 CAGGUGGG G AAACUAAG 6796 CUUAGUUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCCACCUG 7151 41 GAAACUAA G GCCCAGAG 6797 CUCUGGGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUAGUUUC 7152 42 AAACUAAG G CCCAGAGA 5760 UCUCUGGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUUAGUUU 7153 47 AAGGCCCA G AGAAGUGA 6798 UCACUUCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGGGCCUU 7154 49 GGCCCAGA G AAGUGAGG 6799 CCUCACUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCUGGGCC 7155 52 CCAGAGAA G UGAGGACC 5761 GGUCCUCA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUCUCUGG 7156 54 AGAGAAGU G AGGACCCC 6800 GGGGUCCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACUUCUCU 7157 56 AGAAGUGA G GACCCCGC 6801 GCGGGGUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCACUUCU 7158 57 GAAGUGAG G ACCCCGCA 6802 UGCGGGGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUCACUUC 7159 63 AGGACCCC G CAGACUAU 5762 AUAGUCUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GGGGUCCU 7160 66 ACCCCGCA G ACUAUCAA 6803 UUGAUAGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGCGGGGU 7161 80 CAAUCCCA G UCUCUUCC 5763 GGAAGAGA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGGGAUUG 7162 100 CACUCCCU G UGAAGCUC 5764 GAGCUUCA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGGGAGUG 7163 102 CUCCCUGU G AAGCUCUC 6804 GAGAGCUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACAGGGAG 7164 105 CCUGUGAA G CUCUCCAG 5765 CUGGAGAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUCACAGG 7165 113 GCUCUCCA G CAUCAUCG 5766 CGAUGAUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGGAGAGC 7166 121 GCAUCAUC G AGGUCCCA 6805 UGGGACCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GAUGAUGC 7167 123 AUCAUCGA G GUCCCAUC 6806 GAUGGGAC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCGAUGAU 7168 124 UCAUCGAG G UCCCAUCA 5767 UGAUGGGA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUCGAUGA 7169 133 UCCCAUCA G CCCUUGCC 5768 GGCAAGGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGAUGGGA 7170 139 CAGCCCUU G CCCUGUUG 5769 CAACAGGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAGGGCUG 7171 144 CUUGCCCU G UUGGAUGA 5770 UCAUCCAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGGGCAAG 7172 147 GCCCUGUU G GAUGAAUA 6807 UAUUCAUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AACAGGGC 7173 148 CCCUGUUG G AUGAAUAG 6808 CUAUUCAU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAACAGGG 7174 151 UGUUGGAU G AAUAGGCA 6809 UGCCUAUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUCCAACA 7175 156 GAUGAAUA G GCACCUCU 6810 AGAGGUGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UAUUCAUC 7176 157 AUGAAUAG G CACCUCUG 5771 CAGAGGUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUAUUCAU 7177 165 GCACCUCU G GAAGAGCC 6811 GGCUCUUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGAGGUGC 7178 166 CACCUCUG G AAGAGCCA 6812 UGGCUCUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAGAGGUG 7179 169 CUCUGGAA G AGCCAACU 6813 AGUUGGCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUCCAGAG 7180 171 CUGGAAGA G CCAACUGU 5772 ACAGUUGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCUUCCAG 7181 178 AGCCAACU G UGUGAGAU 5773 AUCUCACA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGUUGGCU 7182 180 CCAACUGU G UGAGAUGG 5774 CCAUCUCA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACAGUUGG 7183 182 AACUGUGU G AGAUGGUG 6814 CACCAUCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACACAGUU 7184 184 CUGUGUGA G AUGGUGCA 6815 UGCACCAU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCACACAG 7185 187 UGUGAGAU G GUGCAGCC 6816 GGCUGCAC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUCUCACA 7186 188 GUGAGAUG G UGCAGCCC 5775 GGGCUGCA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAUCUCAC 7187 190 GAGAUGGU G CAGCCCAG 5776 CUGGGCUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACCAUCUC 7188 193 AUGGUGCA G CCCAGUGG 5777 CCACUGGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGCACCAU 7189 198 GCAGCCCA G UGGUGGCC 5778 GGCCACCA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGGGCUGC 7190 200 AGCCCAGU G GUGGCCCG 6817 CGGGCCAC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACUGGGCU 7191 201 GCCCAGUG G UGGCCCGG 5779 CCGGGCCA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CACUGGGC 7192 203 CCAGUGGU G GCCCGGCA 6818 UGCCGGGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACCACUGG 7193 204 CAGUGGUG G CCCGGCAG 5780 CUGCCGGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CACCACUG 7194 208 GGUGGCCC G GCAGCAGA 6819 UCUGCUGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GGGCCACC 7195 209 GUGGCCCG G CAGCAGAU 5781 AUCUGCUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CGGGCCAC 7196 212 GCCCGGCA G CAGAUCAG 5782 CUGAUCUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGCCGGGC 7197 215 CGGCAGCA G AUCAGGAC 6820 GUCCUGAU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGCUGCCG 7198 220 GCAGAUCA G GACGUACU 6821 AGUACGUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGAUCUGC 7199 221 CAGAUCAG G ACGUACUG 6822 CAGUACGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUGAUCUG 7200 224 AUCAGGAC G UACUGGGC 5783 GCCCAGUA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GUCCUGAU 7201 229 GACGUACU G GGCGAAGA 6823 UCUUCGCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGUACGUC 7202 230 ACGUACUG G GCGAAGAG 6824 CUCUUCGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAGUACGU 7203 231 CGUACUGG G CGAAGAGU 5784 ACUCUUCG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCAGUACG 7204 233 UACUGGGC G AAGAGUCU 6825 AGACUCUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GCCCAGUA 7205 236 UGGGCGAA G AGUCUCCU 6826 AGGAGACU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUCGCCCA 7206 238 GGCGAAGA G UCUCCUCU 5785 AGAGGAGA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCUUCGCC 7207 247 UCUCCUCU G GGGAAGCC 6827 GGCUUCCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGAGGAGA 7208 248 CUCCUCUG G GGAAGCCA 6828 UGGCUUCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAGAGGAG 7209 249 UCCUCUGG G GAAGCCAG 6829 CUGGCUUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCAGAGGA 7210 250 CCUCUGGG G AAGCCAGC 6830 GCUGGCUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCCAGAGG 7211 253 CUGGGGAA G CCAGCCAU 5786 AUGGCUGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUCCCCAG 7212 257 GGAAGCCA G CCAUGCUG 5787 CAGCAUGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGGCUUCC 7213 262 CCAGCCAU G CUGCACCU 5788 AGGUGCAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUGGCUGG 7214 265 GCCAUGCU G CACCUGCC 5789 GGCAGGUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGCAUGGC 7215 271 CUGCACCU G CCUUCAGA 5790 UCUGAAGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGGUGCAG 7216 278 UGCCUUCA G AACAGGGC 6831 GCCCUGUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGAAGGCA 7217 283 UCAGAACA G GGCGCUCC 6832 GGAGCGCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGUUCUGA 7218 284 CAGAACAG G GCGCUCCU 6833 AGGAGCGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUGUUCUG 7219 285 AGAACAGG G CGCUCCUG 5791 CAGGAGCG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCUGUUCU 7220 287 AACAGGGC G CUCCUGAG 5792 CUCAGGAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GCCCUGUU 7221 293 GCGCUCCU G AGACCCUC 6834 GAGGGUCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGGAGCGC 7222

295 GCUCCUGA G ACCCUCCA 6835 UGGAGGGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCAGGAGC 7223 304 ACCCUCCA G CGCUGCCU 5793 AGGCAGCG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGGAGGGU 7224 306 CCUCCAGC G CUGCCUGG 5794 CCAGGCAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GCUGGAGG 7225 309 CCAGCGCU G CCUGGAGG 5795 CCUCCAGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGCGCUGG 7226 313 CGCUGCCU G GAGGAGAA 6836 UUCUCCUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGGCAGCG 7227 314 GCUGCCUG G AGGAGAAU 6837 AUUCUCCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAGGCAGC 7228 316 UGCCUGGA G GAGAAUCA 6838 UGAUUCUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCCAGGCA 7229 317 GCCUGGAG G AGAAUCAA 6839 UUGAUUCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUCCAGGC 7230 319 CUGGAGGA G AAUCAAGA 6840 UCUUGAUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCCUCCAG 7231 326 AGAAUCAA G AGCUCCGA 6841 UCGGAGCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUGAUUCU 7232 328 AAUCAAGA G CUCCGAGA 5796 UCUCGGAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCUUGAUU 7233 333 AGAGCUCC G AGAUGCCA 6842 UGGCAUCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GGAGCUCU 7234 335 AGCUCCGA G AUGCCAUC 6843 GAUGGCAU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCGGAGCU 7235 338 UCCGAGAU G CCAUCCGG 5797 CCGGAUGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUCUCGGA 7236 345 UGCCAUCC G GCAGAGCA 6844 UGCUCUGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GGAUGGCA 7237 346 GCCAUCCG G CAGAGCAA 5798 UUGCUCUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CGGAUGGC 7238 349 AUCCGGCA G AGCAACCA 6845 UGGUUGCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGCCGGAU 7239 351 CCGGCAGA G CAACCAGA 5799 UCUGGUUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCUGCCGG 7240 358 AGCAACCA G AUUCUGCG 6846 CGCAGAAU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGGUUGCU 7241 364 CAGAUUCU G CGGGAGCG 5800 CGCUCCCG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGAAUCUG 7242 366 GAUUCUGC G GGAGCGCU 6847 AGCGCUCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GCAGAAUC 7243 367 AUUCUGCG G GAGCGCUG 6848 CAGCGCUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CGCAGAAU 7244 368 UUCUGCGG G AGCGCUGC 6849 GCAGCGCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCGCAGAA 7245 370 CUGCGGGA G CGCUGCGA 5801 UCGCAGCG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCCCGCAG 7246 372 GCGGGAGC G CUGCGAGG 5802 CCUCGCAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GCUCCCGC 7247 375 GGAGCGCU G CGAGGAGC 5803 GCUCCUCG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGCGCUCC 7248 377 AGCGCUGC G AGGAGCUU 6850 AAGCUCCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GCAGCGCU 7249 379 CGCUGCGA G GAGCUUCU 6851 AGAAGCUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCGCACCG 7250 380 GCUGCGAG G AGCUUCUG 6852 CAGAAGCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUCGCAGC 7251 382 UGCGAGGA G CUUCUGCA 5804 UGCAGAAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCCUCGCA 7252 388 GAGCUUCU G CAUUUCCA 5805 UGGAAAUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGAAGCUC 7253 398 AUUUCCAA G CCAGCCAG 5806 CUGGCUGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUGCAAAU 7254 402 CCAAGCCA G CCACAGGG 5807 CCCUCUGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGGCUUCG 7255 406 GCCAGCCA G AGGGACCA 6853 UCCUCCCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCCCUGCC 7256 408 CAGCCAGA G CCACGAGA 6854 UCUCCUCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCUCCCUC 7257 409 ACCCAGAC G GAGCAGAA 6855 UUCUCCUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUCUCGCU 7258 410 CCCACACC G AGCAGAAC 6856 CUUCUCCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCUCUGCC 7259 412 CAGAGGCA G GAGAACGA 6657 UCCUUCUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCCCUCUC 7260 413 AGAGGGAG G ACAACCAC 6858 CUCCUUCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUCCCUCU 7261 415 AGGGAGGA G AAGGACUU 6859 AACUCCUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCCUCCCU 7262 418 CACGAGAA G GACUUCCU 6860 AGGAACUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUCUCCUC 7263 419 AGCAGAAG G ACUUCCUC 6861 GAGCAACU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUUCUCCU 7264 421 GACAACGA G UUCCUCAU 5808 AUCAGCAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCCUUCUC 7265 430 UUCCUCAU G UCCAACUU 5809 AACUUCCA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUCAGCAA 7266 432 CCUCAUCU G CAAGUUCC 5810 CGAACUUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACAUGAGC 7267 436 AUCUCCAA G UUCCACCA 5811 UCCUCCAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUCCACAU 7268 442 AACUUCCA G CACCCCAC 6862 CUCCCCUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCCAACUU 7269 443 ACUUCCAC G ACCCCACC 6863 CCUCCCCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUCCAACU 7270 445 UUCCACCA G CCCACCAA 6864 UUCCUCCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCCUCCAA 7271 446 UCCACCAC G CCACCAAA 5812 UUUCCUCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUCCUCCA 7272 450 CCACCCCA G CAAACUCC 6865 CCACUUUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCCCCUCC 7273 451 CACCCCAC G AAACUCCU 6866 ACCACUUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUCCCCUC 7274 457 ACCAAACU G CUCCACAC 6867 CUCUCCAC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACUUUCCU 7275 458 CCAAACUC G UCCACACA 5813 UCUCUCCA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CACUUUCC 7276 460 AAACUCCU G CACACACU 6868 ACUCUCUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACCACUUU 7277 461 AACUCCUC G ACACACUC 6869 CACUCUCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CACCACUU 7278 463 CUGGUCCA G ACACUCCC 6870 CCCACUCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCCACCAC 7279 465 CCUCCACA G ACUCCCCC 6871 CCCCCACU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCUCCACC 7280 470 ACACACUC G CCCUCCAC 6872 CUCCACCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CACUCUCU 7281 471 CACACUCC G CCUCCACA 5814 UCUCCACC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCACUCUC 7282 475 CUCCCCCU G CACAACCU 6873 ACCUUCUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACCCCCAC 7283 476 UCGGCCUG G AGAACCUC 6874 CACCUUCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CACCCCCA 7284 478 GGCCUGGA G AACCUCCA 6875 UCCACCUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCCACCCC 7285 481 CUGGACAA G CUCCAUCU 5815 AGAUCCAC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUCUCCAC 7286 485 AGAAGCUC G AUCUGAAG 6876 CUUCAGAU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GAGCUUCU 7287 490 CUCGAUCU G AAGAGGCA 6877 UGCCUCUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGAUCGAG 7288 493 GAUCUGAA G AGGCAGAA 6878 UUCUGCCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUCAGAUC 7289 495 UCUGAAGA G GCAGAAGG 6879 CCUUCUGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCUUCAGA 7290 496 CUGAAGAG G CAGAAGGA 5816 UCCUUCUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUCUUCAG 7291 499 AAGAGGCA G AAGGAGCA 6880 UGCUCCUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGCCUCUU 7292 502 AGGCAGAA G GAGCAGGC 6881 GCCUGCUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUCUGCCU 7293 503 GGCAGAAG G AGCAGGCU 6882 AGCCUGCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUUCUGCC 7294 505 CAGAAGGA G CAGGCUCU 5817 AGAGCCUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCCUUCUG 7295 508 AAGGAGCA G GCUCUGCG 6883 CGCAGAGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGCUCCUU 7296 509 AGGAGCAG G CUCUGCGG 5818 CCGCAGAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUGCUCCU 7297 514 CAGGCUCU G CGGGAGGU 5819 ACCUCCCG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGAGCCUG 7298 516 GGCUCUGC G GGAGGUGG 6884 CCACCUCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GCAGAGCC 7299 517 GCUCUGCG G GAGGUGGA 6885 UCCACCUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CGCAGAGC 7300 518 CUCUGCGG G AGGUGGAG 6886 CUCCACCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCGCAGAG 7301 520 CUGCGGGA G GUGGAGCA 6887 UGCUCCAC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCCCGCAG 7302 521 UGCGGGAG G UGGAGCAC 5820 GUGCUCCA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUCCCGCA 7303 523 CGGGAGGU G GAGCACCU 6888 AGGUGCUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACCUCCCG 7304 524 GGGAGGUG G AGCACCUG 6889 CAGGUGCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CACCUCCC 7305 526 GAGGUGGA G CACCUGAA 5821 UUCAGGUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCCACCUC 7306

532 GAGCACCU G AAGAGAUG 6890 CAUCUCUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGGUGCUC 7307 535 CACCUGAA G AGAUGCCA 6891 UGGCAUCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUCAGGUG 7308 537 CCUGAAGA G AUGCCAGC 6892 GCUGGCAU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCUUCAGG 7309 540 GAAGAGAU G CCAGCAGC 5822 GCUGCUGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUCUCUUC 7310 544 AGAUGCCA G CAGCAGAU 5823 AUCUGCUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGGCAUCU 7311 547 UGCCAGCA G CAGAUGGC 5824 GCCAUCUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGCUGGCA 7312 550 CAGCAGCA G AUGGCUGA 6893 UCAGCCAU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGCUGCUG 7313 553 CAGCAGAU G GCUGAGGA 6894 UCCUCAGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUCUGCUG 7314 554 AGCAGAUG G CUGAGGAC 5825 GUCCUCAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAUCUGCU 7315 557 AGAUGGCU G AGGACAAG 6895 CUUGUCCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGCCAUCU 7316 559 AUGGCUGA G GACAAGGC 6896 GCCUUGUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCAGCCAU 7317 560 UGGCUGAG G ACAAGGCC 6897 GGCCUUGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUCAGCCA 7318 565 GAGGACAA G GCCUCUGU 6898 ACAGAGGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUGUCCUC 7319 566 AGGACAAG G CCUCUGUG 5826 CACAGAGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUUGUCCU 7320 572 AGGCCUCU G UGAAAGCC 5827 GGCUUUCA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGAGGCCU 7321 574 GCCUCUGU G AAAGCCCA 6899 UGGGCUUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACAGAGGC 7322 578 CUGUGAAA G CCCAGGUG 5828 CACCUGGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUUCACAG 7323 583 AAAGCCCA G GUGACGUC 6900 GACGUCAC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGGGCUUU 7324 584 AAGCCCAG G UGACGUCC 5829 GGACGUCA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUGGGCUU 7325 586 GCCCAGGU G ACGUCCUU 6901 AAGGACGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACCUGGGC 7326 589 CAGGUGAC G UCCUUGCU 5830 AGCAAGGA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GUCACCUG 7327 595 ACGUCCUU G CUCGGGGA 5831 UCCCCGAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAGGACGU 7328 599 CCUUGCUC G GGGAGCUG 6902 CAGCUCCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GAGCAAGG 7329 600 CUUGCUCG G GGAGCUGC 6903 GCAGCUCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CGAGCAAG 7330 601 UUGCUCGG G GAGCUGCA 6904 UGCAGCUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCGAGCAA 7331 602 UGCUCGGG G AGCUGCAG 6905 CUGCAGCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCCGAGCA 7332 604 CUCGGGGA G CUGCAGGA 5832 UCCUGCAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCCCCGAG 7333 607 GGGGAGCU G CAGGAGAG 5833 CUCUCCUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGCUCCCC 7334 610 GAGCUGCA G GAGAGCCA 6906 UGGCUCUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGCAGCUC 7335 611 AGCUGCAG G AGAGCCAG 6907 CUGGCUCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUGCAGCU 7336 613 CUGCAGGA G AGCCAGAG 6908 CUCUGGCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCCUGCAG 7337 615 GCAGGAGA G CCAGAGUC 5834 GACUCUGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCUCCUGC 7338 619 GAGAGCCA G AGUCGCUU 6909 AAGCGACU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGGCUCUC 7339 621 GAGCCAGA G UCGCUUGG 5835 CCAAGCGA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCUGGCUC 7340 624 CCAGAGUC G CUUGGAGG 5836 CCUCCAAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GACUCUGG 7341 628 AGUCGCUU G GAGGCUGC 6910 GCAGCCUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAGCGACU 7342 629 GUCGCUUG G AGGCUGCC 6911 GGCAGCCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAAGCGAC 7343 631 CGCUUGGA G GCUGCCAC 6912 GUGGCAGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCCAAGCG 7344 632 GCUUGGAG G CUGCCACU 5837 AGUGGCAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUCCAAGC 7345 635 UGGAGGCU G CCACUAAG 5838 CUUAGUGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGCCUCCA 7346 643 GCCACUAA G GAAUGCCA 6913 UGGCAUUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUAGUGGC 7347 644 CCACUAAG G AAUGCCAG 6914 CUGGCAUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUUAGUGG 7348 648 UAAGGAAU G CCAGGCUC 5839 GAGCCUGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUUCCUUA 7349 652 GAAUGCCA G GCUCUGGA 6915 UCCAGAGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGGCAUUC 7350 653 AAUGCCAG G CUCUGGAG 5840 CUCCAGAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUGGCAUU 7351 658 CAGGCUCU G GAGGGUCG 6916 CGACCCUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGAGCCUG 7352 659 AGGCUCUG G AGGGUCGG 6917 CCGACCCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAGAGCCU 7353 661 GCUCUGGA G GGUCGGGC 6918 GCCCGACC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCCAGAGC 7354 662 CUCUGGAG G GUCGGGCC 6919 GGCCCGAC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUCCAGAG 7355 663 UCUGGAGG G UCGGGCCC 5841 GGGCCCGA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCUCCAGA 7356 666 GGAGGGUC G GGCCCGGG 6920 CCCGGGCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GACCCUCC 7357 667 GAGGGUCG G GCCCGGGC 6921 GCCCGGGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CGACCCUC 7358 668 AGGGUCGG G CCCGGGCG 5842 CGCCCGGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCGACCCU 7359 672 UCGGGCCC G GGCGGCCA 6922 UGGCCGCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GGGCCCGA 7360 673 CGGGCCCG G GCGGCCAG 6923 CUGGCCGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CGGGCCCG 7361 674 GGGCCCGG G CGGCCAGC 5843 GCUGGCCG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCGGGCCC 7362 676 GCCCGGGC G GCCAGCGA 6924 UCGCUGGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GCCCGGGC 7363 677 CCCGGGCG G CCAGCGAG 5844 CUCGCUGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CGCCCGGG 7364 681 GGCGGCCA G CGAGCAGG 5845 CCUGCUCG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGGCCGCC 7365 683 CGGCCAGC G AGCAGGCG 6925 CGCCUGCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GCUGGCCG 7366 685 GCCAGCGA G CAGGCGCG 5846 CGCGCCUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCGCUGGC 7367 688 AGCGAGCA G GCGCGGCA 6926 UGCCGCGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGCUCGCU 7368 689 GCGAGCAG G CGCGGCAG 5847 CUGCCGCG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUGCUCGC 7369 691 GAGCAGGC G CGGCAGCU 5848 AGCUGCCG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GCCUGCUC 7370 693 GCAGGCGC G GCAGCUGG 6927 CCAGCUGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GCGCCUGC 7371 694 CAGGCGCG G CAGCUGGA 5849 UCCAGCUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CGCGCCUG 7372 697 GCGCGGCA G CUGGAGAG 5850 CUCUCCAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGCCGCGC 7373 700 CGGCAGCU G GAGAGUGA 6928 UCACUCUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGCUGCCG 7374 701 GGCAGCUG G AGAGUGAG 6929 CUCACUCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAGCUGCC 7375 703 CAGCUGGA G AGUGAGCG 6930 CGCUCACU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCCAGCUG 7376 705 GCUGGAGA G UGAGCGCG 5851 CGCGCUCA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCUCCAGC 7377 707 UGGAGAGU G AGCGCGAG 6931 CUCGCGCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACUCUCCA 7378 709 GAGAGUGA G CGCGAGGC 5852 GCCUCGCG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCACUCUC 7379 711 GAGUGAGC G CGAGGCGC 5853 GCGCCUCG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GCUCACUC 7380 713 GUGAGCGC G AGGCGCUG 6932 CAGCGCCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GCGCUCAC 7381 715 GAGCGCGA G GCGCUGCA 6933 UGCAGCGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCGCGCUC 7382 716 AGCGCGAG G CGCUGCAG 5854 CUGCAGCG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUCGCGCU 7383 718 CGCGAGGC G CUGCAGCA 5855 UGCUGCAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GCCUCGCG 7384 721 GAGGCGCU G CAGCAGCA 5856 UGCUGCUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGCGCCUC 7385 724 GCGCUGCA G CAGCAGCA 5857 UGCUGCUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGCAGCGC 7386 727 CUGCAGCA G CAGCACAG 5858 CUGUGCUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGCUGCAG 7387 730 CAGCAGCA G CACAGCGU 5859 ACGCUGUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGCUGCUG 7388 735 GCAGCACA G CGUGCAGG 5860 CCUGCACG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGUGCUGC 7389 737 AGCACAGC G UGCAGGUG 5861 CACCUGCA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG

GCUGUGCU 7390 739 CACAGCGU G CAGGUGGA 5862 UCCACCUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACGCUGUG 7391 742 AGCGUGCA G GUGGACCA 6934 UGGUCCAC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGCACGCU 7392 743 GCGUGCAG G UGGACCAG 5863 CUGGUCCA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUGCACGC 7393 745 GUGCAGGU G GACCAGCU 6935 AGCUGGUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACCUGCAC 7394 746 UGCAGGUG G ACCAGCUG 6936 CAGCUGGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CACCUGCA 7395 751 GUGGACCA G CUGCGCAU 5864 AUGCGCAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGGUCCAC 7396 754 GACCAGCU G CGCAUGCA 5865 UGCAUGCG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGCUGGUC 7397 756 CCAGCUGC G CAUGCAGG 5866 CCUGCAUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GCAGCUGG 7398 760 CUGCGCAU G CAGGGCCA 5867 UGGCCCUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUGCGCAG 7399 763 CGCAUGCA G GGCCAGAG 6937 CUCUGGCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGCAUGCG 7400 764 GCAUGCAG G GCCAGAGC 6938 GCUCUGGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUGCAUGC 7401 765 CAUGCAGG G CCAGAGCG 5868 CGCUCUGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCUGCAUG 7402 769 CAGGGCCA G AGCGUGGA 6939 UCCACGCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGGCCCUG 7403 771 GGGCCAGA G CGUGGAGG 5869 CCUCCACG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCUGGCCC 7404 773 GCCAGAGC G UGGAGGCC 5870 GGCCUCCA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GCUCUGGC 7405 775 CAGAGCGU G GAGGCCGC 6940 GCGGCCUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACGCUCUG 7406 776 AGAGCGUG G AGGCCGCG 6941 CGCGGCCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CACGCUCU 7407 778 AGCGUGGA G GCCGCGCU 6942 AGCGCGGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCCACGCU 7408 779 GCGUGGAG G CCGCGCUC 5871 GAGCGCGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUCCACGC 7409 782 UGGAGGCC G CGCUCCGC 5872 GCGGAGCG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GGCCUCCA 7410 784 GAGGCCGC G CUCCGCAU 5873 AUGCGGAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GCGGCCUC 7411 789 CGCGCUCC G CAUGGAGC 5874 GCUCCAUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GGAGCGCG 7412 793 CUCCGCAU G GAGCGCCA 6943 UGGCGCUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUGCGGAG 7413 794 UCCGCAUG G AGCGCCAG 6944 CUGGCGCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAUGCGGA 7414 796 CGCAUGGA G CGCCAGGC 5875 GCCUGGCG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCCAUGCG 7415 798 CAUGGAGC G CCAGGCCG 5876 CGGCCUGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GCUCCAUG 7416 802 GAGCGCCA G GCCGCCUC 6945 GAGGCGGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGGCGCUC 7417 803 AGCGCCAG G CCGCCUCG 5877 CGAGGCGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUGGCGCU 7418 806 GCCAGGCC G CCUCGGAG 5878 CUCCGAGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GGCCUGGC 7419 811 GCCGCCUC G GAGGAGAA 6946 UUCUCCUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GAGGCGGC 7420 812 CCGCCUCG G AGGAGAAG 6947 CUUCUCCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CGAGGCGG 7421 814 GCCUCGGA G GAGAAGAG 6948 CUCUUCUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCCGAGGC 7422 815 CCUCGGAG G AGAAGAGG 6949 CCUCUUCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUCCGAGG 7423 817 UCGGAGGA G AAGAGGAA 6950 UUCCUCUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCCUCCGA 7424 820 GAGGAGAA G AGGAAGCU 6951 AGCUUCCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUCUCCUC 7425 822 GGAGAAGA G GAAGCUGG 6952 CCAGCUUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCUUCUCC 7426 823 GAGAAGAG G AAGCUGGC 6953 GCCAGCUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUCUUCUC 7427 826 AAGAGGAA G CUGGCCCA 5879 UGGGCCAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUCCUCUU 7428 829 AGGAAGCU G GCCCAGUU 6954 AACUGGGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGCUUCCU 7429 830 GGAAGCUG G CCCAGUUG 5880 CAACUGGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAGCUUCC 7430 835 CUGGCCCA G UUGCAGGU 5881 ACCUGCAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGGGCCAG 7431 838 GCCCAGUU G CAGGUGGC 5882 GCCACCUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AACUGGGC 7432 841 CAGUUGCA G GUGGCCUA 6955 UAGGCCAC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGCAACUG 7433 842 AGUUGCAG G UGGCCUAU 5883 AUAGGCCA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUGCAACU 7434 844 UUGCAGGU G GCCUAUCA 6956 UGAUAGGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACCUGCAA 7435 845 UGCAGGUG G CCUAUCAC 5884 GUGAUAGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CACCUGCA 7436 856 UAUCACCA G CUCUUCCA 5885 UGGAAGAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGGUGAUA 7437 866 UCUUCCAA G AAUACGAC 6957 GUCGUAUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUGGAAGA 7438 872 AAGAAUAC G ACAACCAC 6958 GUGGUUGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GUAUUCUU 7439 886 CACAUCAA G AGCAGCGU 6959 ACGCUGCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUGAUGUG 7440 888 CAUCAAGA G CAGCGUGG 5886 CCACGCUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCUUGAUG 7441 891 CAAGAGCA G CGUGGUGG 5887 CCACCACG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGCUCUUG 7442 893 AGAGCAGC G UGGUGGGC 5888 GCCCACCA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GCUGCUCU 7443 895 AGCAGCGU G GUGGGCAG 6960 CUGCCCAC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACGCUGCU 7444 896 GCAGCGUG G UGGGCAGU 5889 ACUGCCCA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CACGCUGC 7445 898 AGCGUGGU G GGCAGUGA 6961 UCACUGCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACCACGCU 7446 899 GCGUGGUG G GCAGUGAG 6962 CUCACUGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CACCACGC 7447 900 CGUGGUGG G CAGUGAGC 5890 GCUCACUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCACCACG 7448 903 GGUGGGCA G UGAGCGGA 5891 UCCGCUCA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGCCCACC 7449 905 UGGGCAGU G AGCGGAAG 6963 CUUCCGCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACUGCCCA 7450 907 GGCAGUGA G CGGAAGCG 5892 CGCUUCCG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCACUGCC 7451 909 CAGUGAGC G GAAGCGAG 6964 CUCGCUUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GCUCACUG 7452 910 AGUGAGCG G AAGCGAGG 6965 CCUCGCUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CGCUCACU 7453 913 GAGCGGAA G CGAGGAAU 5893 AUUCCUCG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUCCGCUC 7454 915 GCGGAAGC G AGGAAUGC 6966 GCAUUCCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GCUUCCGC 7455 917 GGAAGCGA G GAAUGCAG 6967 CUGCAUUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCGCUUCC 7456 918 GAAGCGAG G AAUGCAGC 6968 GCUGCAUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUCGCUUC 7457 922 CGAGGAAU G CAGCUGGA 5894 UCCAGCUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUUCCUCG 7458 925 GGAAUGCA G CUGGAAGA 5895 UCUUCCAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGCAUUCC 7459 928 AUGCAGCU G GAAGAUCU 6969 AGAUCUUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGCUGCAU 7460 929 UGCAGCUG G AAGAUCUC 6970 GAGAUCUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAGCUGCA 7461 932 AGCUGGAA G AUCUCAAA 6971 UUUGAGAU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUCCAGCU 7462 943 CUCAAACA G CAGCUCCA 5896 UGGAGCUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGUUUGAG 7463 946 AAACAGCA G CUCCAGCA 5897 UGCUGGAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGCUGUUU 7464 952 CAGCUCCA G CAGGCCGA 5898 UCGGCCUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGGAGCUG 7465 955 CUCCAGCA G GCCGAGGA 6972 UCCUCGGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGCUGGAG 7466 956 UCCAGCAG G CCGAGGAG 5899 CUCCUCGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUGCUGGA 7467 959 AGCAGGCC G AGGAGGCC 6973 GGCCUCCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GGCCUGCU 7468 961 CAGGCCGA G GAGGCCCU 6974 AGGGCCUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCGGCCUG 7469 962 AGGCCGAG G AGGCCCUG 6975 CAGGGCCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUCGGCCU 7470 964 GCCGAGGA a GCCCUGGU 6976 ACCAGGGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCCUCGGC 7471 965 CCGAGGAG G CCCUGGUG 5900 CACCAGGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUCCUCGG 7472 970 GAGGCCCU G GUGGCCAA 6977 UUGGCCAC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGGGCCUC 7473

971 AGGCCCUG G UGGCCAAA 5901 UUUGGCCA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAGGGCCU 7474 973 GCCCUGGU G GCCAAACA 6978 UGUUUGGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACCAGGGC 7475 974 CCCUGGUG G CCAAACAG 5902 CUGUUUGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CACCAGGG 7476 982 GCCAAACA G GAGGUGAU 6979 AUCACCUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGUUUGGC 7477 983 CCAAACAG G AGGUGAUC 6980 GAUCACCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUGUUUGG 7478 985 AAACAGGA G GUGAUCGA 6981 UCGAUCAC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCCUGUUU 7479 986 AACAGGAG G UGAUCGAU 5903 AUCGAUCA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUCCUGUU 7480 988 CAGGAGGU G AUCGAUAA 6982 UUAUCGAU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACCUCCUG 7481 992 AGGUGAUC G AUAAGCUG 6983 CAGCUUAU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GAUCACCU 7482 997 AUCGAUAA G CUGAAGGA 5904 UCCUUCAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUAUCGAU 7483 1000 GAUAAGCU G AAGGAGGA 6984 UCCUCCUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGCUUAUC 7484 1003 AAGCUGAA G GAGGAGGC 6985 GCCUCCUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUCAGCUU 7485 1004 AGCUGAAG G AGGAGGCC 6986 GGCCUCCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUUCAGCU 7486 1006 CUGAAGGA G GAGGCCGA 6987 UCGGCCUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCCUUCAG 7487 1007 UGAAGGAG G AGGCCGAG 6988 CUCGGCCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUCCUUCA 7488 1009 AAGGAGGA G GCCGAGCA 6989 UGCUCGGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCCUCCUU 7489 1010 AGGAGGAG G CCGAGCAG 5905 CUGCUCGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUCCUCCU 7490 1013 AGGAGGCC G AGCAGCAC 6990 GUGCUGCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GGCCUCCU 7491 1015 GAGGCCGA G CAGCACAA 5906 UUGUGCUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCGGCCUC 7492 1018 GCCGAGCA G CACAAGAU 5907 AUCUUGUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGCUCGGC 7493 1024 CAGCACAA G AUUGUGAU 6991 AUCACAAU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUGUGCUG 7494 1028 ACAAGAUU G UGAUGGAG 5908 CUCCAUCA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAUCUUGU 7495 1030 AAGAUUGU G AUGGAGAC 6992 GUCUCCAU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACAAUCUU 7496 1033 AUUGUGAU G GAGACCGU 6993 ACGGUCUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUCACAAU 7497 1034 UUGUGAUG G AGACCGUU 6994 AACGGUCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAUCACAA 7498 1036 GUGAUGGA G ACCGUUCC 6995 GGAACGGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCCAUCAC 7499 1040 UGGAGACC G UUCCGGUG 5909 CACCGGAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GGUCUCCA 7500 1045 ACCGUUCC G GUGCUGAA 6996 UUCAGCAC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GGAACGGU 7501 1046 CCGUUCCG G UGCUGAAG 5910 CUUCAGCA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CGGAACGG 7502 1048 GUUCCGGU G CUGAAGGC 5911 GCCUUCAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACCGGAAC 7503 1051 CCGGUGCU G AAGGCCCA 6997 UGGGCCUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGCACCGG 7504 1054 GUGCUGAA G GCCCAGGC 6998 GCCUGGGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUCAGCAC 7505 1055 UGCUGAAG G CCCAGGCG 5912 CGCCUGGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUUCAGCA 7506 1060 AAGGCCCA G GCGGAUAU 6999 AUAUCCGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGGGCCUU 7507 1061 AGGCCCAG G CGGAUAUC 5913 GAUAUCCG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUGGGCCU 7508 1063 GCCCAGGC G GAUAUCUA 7000 UAGAUAUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GCCUGGGC 7509 1064 CCCAGGCG G AUAUCUAC 7001 GUAGAUAU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CGCCUGGG 7510 1075 AUCUACAA G GCGGACUU 7002 AAGUCCGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUGUAGAU 7511 1076 UCUACAAG G CGGACUUC 5914 GAAGUCCG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUUGUAGA 7512 1078 UACAAGGC G GACUUCCA 7003 UGGAAGUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GCCUUGUA 7513 1079 ACAAGGCG G ACUUCCAG 7004 CUGGAAGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CGCCUUGU 7514 1087 GACUUCCA G GCUGAGAG 7005 CUCUCAGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGGAAGUC 7515 1088 ACUUCCAG G CUGAGAGG 5915 CCUCUCAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUGGAAGU 7516 1091 UCCAGGCU G AGAGGCAG 7006 CUGCCUCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGCCUGGA 7517 1093 CAGGCUGA G AGGCAGGC 7007 GCCUGCCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCAGCCUG 7518 1095 GGCUGAGA G GCAGGCCC 7008 GGGCCUGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCUCAGCC 7519 1096 GCUGAGAG G CAGGCCCG 5916 CGGGCCUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUCUCAGC 7520 1099 GAGAGGCA G GCCCGGGA 7009 UCCCGGGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGCCUCUC 7521 1100 AGAGGCAG G CCCGGGAG 5917 CUCCCGGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUGCCUCU 7522 1104 GCAGGCCC G GGAGAAGC 7010 GCUUCUCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GGGCCUGC 7523 1105 CAGGCCCG G GAGAAGCU 7011 AGCUUCUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CGGGCCUG 7524 1106 AGGCCCGG G AGAAGCUG 7012 CAGCUUCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCGGGCCU 7525 1108 GCCCGGGA G AAGCUGGC 7013 GCCAGCUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCCCGGGC 7526 1111 CGGGAGAA G CUGGCCGA 5918 UCGGCCAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUCUCCCG 7527 1114 GAGAAGCU G GCCGAGAA 7014 UUCUCGGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGCUUCUC 7528 1115 AGAAGCUG G CCGAGAAG 5919 CUUCUCGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAGCUUCU 7529 1118 AGCUGGCC G AGAAGAAG 7015 CUUCUUCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GGCCAGCU 7530 1120 CUGGCCGA G AAGAAGGA 7016 UCCUUCUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCGGCCAG 7531 1123 GCCGAGAA G AAGGAGCU 7017 AGCUCCUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUCUCGGC 7532 1126 GAGAAGAA G GAGCUCCU 7018 AGGAGCUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUCUUCUC 7533 1127 AGAAGAAG G AGCUCCUG 7019 CAGGAGCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUUCUUCU 7534 1129 AAGAAGGA G CUCCUGCA 5920 UGCAGGAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCCUUCUU 7535 1135 GAGCUCCU G CAGGAGCA 5921 UGCUCCUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGGAGCUC 7536 1138 CUCCUGCA G GAGCAGCU 7020 AGCUGCUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGCAGGAG 7537 1139 UCCUGCAG G AGCAGCUG 7021 CAGCUGCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUGCAGGA 7538 1141 CUGCAGGA G CAGCUGGA 5922 UCCAGCUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCCUGCAG 7539 1144 CAGGAGCA G CUGGAGCA 5923 UGCUCCAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGCUCCUG 7540 1147 GAGCAGCU G GAGCAGCU 7022 AGCUGCUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGCUGCUC 7541 1148 AGCAGCUG G AGCAGCUG 7023 CAGCUGCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAGCUGCU 7542 1150 CAGCUGGA G CAGCUGCA 5924 UGCAGCUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCCAGCUG 7543 1153 CUGGAGCA G CUGCAGAG 5925 CUCUGCAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGCUCCAG 7544 1156 GAGCAGCU G CAGAGGGA 5926 UCCCUCUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGCUGCUC 7545 1159 CAGCUGCA G AGGGAGUA 7024 UACUCCCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGCAGCUG 7546 1161 GCUGCAGA G GGAGUACA 7025 UGUACUCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCUGCAGC 7547 1162 CUGCAGAG G GAGUACAG 7026 CUGUACUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUCUGCAG 7548 1163 UGCAGAGG G AGUACAGC 7027 GCUGUACU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCUCUGCA 7549 1165 CAGAGGGA G UACAGCAA 5927 UUGCUGUA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCCCUCUG 7550 1170 GGAGUACA G CAAACUGA 5928 UCAGUUUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGUACUCC 7551 1177 AGCAAACU G AAGGCCAG 7028 CUGGCCUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGUUUGCU 7552 1180 AAACUGAA G GCCAGCUG 7029 CAGCUGGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUCAGUUU 7553 1181 AACUGAAG G CCAGCUGU 5929 ACAGCUGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUUCAGUU 7554 1185 GAAGGCCA G CUGUCAGG 5930 CCUGACAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGGCCUUC 7555 1188 GGCCAGCU G UCAGGAGU 5931 ACUCCUGA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGCUGGCC 7556 1192 AGCUGUCA G GAGUCGGC 7030 GCCGACUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGACAGCU 7557

1193 GCUGUCAG G AGUCGGCC 7031 GGCCGACU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUGACAGC 7558 1195 UGUCAGGA G UCGGCCAG 5932 CUGGCCGA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCCUGACA 7559 1198 CAGGAGUC G GCCAGGAU 7032 AUCCUGGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GACUCCUG 7560 1199 AGGAGUCG G CCAGGAUC 5933 GAUCCUGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CGACUCCU 7561 1203 GUCGGCCA G GAUCGAGG 7033 CCUCGAUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGGCCGAC 7562 1204 UCGGCCAG G AUCGAGGA 7034 UCCUCGAU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUGGCCGA 7563 1208 CCAGGAUC G AGGACAUG 7035 CAUGUCCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GAUCCUGG 7564 1210 AGGAUCGA G GACAUGAG 7036 CUCAUGUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCGAUCCU 7565 1211 GGAUCGAG G ACAUGAGG 7037 CCUCAUGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUCGAUCC 7566 1216 GAGGACAU G AGGAAGCG 7038 CGCUUCCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUGUCCUC 7567 1218 GGACAUGA G GAAGCGGC 7039 GCCGCUUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCAUGUCC 7568 1219 GACAUGAG G AAGCGGCA 7040 UGCCGCUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUCAUGUC 7569 1222 AUGAGGAA G CGGCAUGU 5934 ACAUGCCG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUCCUCAU 7570 1224 GAGGAAGC G GCAUGUCG 7041 CGACAUGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GCUUCCUC 7571 1225 AGGAAGCG G CAUGUCGA 5935 UCGACAUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CGCUUCCU 7572 1229 AGCGGCAU G UCGAGGUC 5936 GACCUCGA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUGCCGCU 7573 1232 GGCAUGUC G AGGUCUCC 7042 GGAGACCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GACAUGCC 7574 1234 CAUGUCGA G GUCUCCCA 7043 UGGGAGAC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCGACAUG 7575 1235 AUGUCGAG G UCUCCCAG 5937 CUGGGAGA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUCGACAU 7576 1243 GUCUCCCA G GCCCCCUU 7044 AAGGGGGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGGGAGAC 7577 1244 UCUCCCAG G CCCCCUUG 5938 CAAGGGGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUGGGAGA 7578 1252 GCCCCCUU G CCCCCCGC 5939 GCGGGGGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAGGGGGC 7579 1259 UGCCCCCC G CCCCUGCC 5940 GGCAGGGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GGGGGGCA 7580 1265 CCGCCCCU G CCUACCUC 5941 GAGGUAGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGGGGCGG 7581 1285 UCUCCCCU G GCCCUGCC 7045 GGCAGGGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGGGGAGA 7582 1286 CUCCCCUG G CCCUGCCC 5942 GGGCAGGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAGGGGAG 7583 1291 CUGGCCCU G CCCAGCCA 5943 UGGCUGGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGGGCCAG 7584 1296 CCUGCCCA G CCAGAGGA 5944 UCCUCUGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGGGCAGG 7585 1300 CCCAGCCA G AGGAGGAG 7046 CUCCUCCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGGCUGGG 7586 1302 CAGCCAGA G GAGGAGCC 7047 GGCUCCUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCUGGCUG 7587 1303 AGCCAGAG G AGGAGCCC 7048 GGGCUCCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUCUGGCU 7588 1305 CCAGAGGA G GAGCCCCC 7049 GGGGGCUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCCUCUGG 7589 1306 CAGAGGAG G AGCCCCCC 7050 GGGGGGCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUCCUCUG 7590 1308 GAGGAGGA G CCCCCCCG 5945 CGGGGGGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCCUCCUC 7591 1316 GCCCCCCC G AGGAGCCA 7051 UGGCUCCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GGGGGGGC 7592 1318 CCCCCCGA G GAGCCACC 7052 GGUGGCUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCGGGGGG 7593 1319 CCCCCGAG G AGCCACCU 7053 AGGUGGCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUCGGGGG 7594 1321 CCCGAGGA G CCACCUGA 5946 UCAGGUGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCCUCGGG 7595 1328 AGCCACCU G ACUUCUGC 7054 GCAGAAGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGGUGGCU 7596 1335 UGACUUCU G CUGUCCCA 5947 UGGGACAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGAAGUCA 7597 1338 CUUCUGCU G UCCCAAGU 5948 ACUUGGGA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGCAGAAG 7598 1345 UGUCCCAA G UGCCAGUA 5949 UACUGGCA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUGGGACA 7599 1347 UCCCAAGU G CCAGUAUC 5950 GAUACUGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACUUGGGA 7600 1351 AAGUGCCA G UAUCAGGC 5951 GCCUGAUA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGGCACUU 7601 1357 CAGUAUCA G GCCCCUGA 7055 UCAGGGGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGAUACUG 7602 1358 AGUAUCAG G CCCCUGAU 5952 AUCAGGGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUGAUACU 7603 1364 AGGCCCCU G AUAUGGAC 7056 GUCCAUAU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGGGGCCU 7604 1369 CCUGAUAU G GACACCCU 7057 AGGGUGUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUAUCAGG 7605 1370 CUGAUAUG G ACACCCUG 7058 CAGGGUGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAUAUCAG 7606 1378 GACACCCU G CAGAUACA 5953 UGUAUCUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGGGUGUC 7607 1381 ACCCUGCA G AUACAUGU 7059 ACAUGUAU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGCAGGGU 7608 1388 AGAUACAU G UCAUGGAG 5954 CUCCAUGA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUGUAUCU 7609 1393 CAUGUCAU G GAGUGCAU 7060 AUGCACUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUGACAUG 7610 1394 AUGUCAUG G AGUGCAUU 7061 AAUGCACU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAUGACAU 7611 1396 GUCAUGGA G UGCAUUGA 5955 UCAAUGCA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCCAUGAC 7612 1398 CAUGGAGU G CAUUGAGU 5956 ACUCAAUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACUCCAUG 7613 1403 AGUGCAUU G AGUAGGGC 7062 GCCCUACU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAUGCACU 7614 1405 UGCAUUGA G UAGGGCCG 5957 CGGCCCUA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCAAUGCA 7615 1408 AUUGAGUA G GGCCGGCC 7063 GGCCGGCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UACUCAAU 7616 1409 UUGAGUAG G GCCGGCCA 7064 UGGCCGGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUACUCAA 7617 1410 UGAGUAGG G CCGGCCAG 5958 CUGGCCGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCUACUCA 7618 1413 GUAGGGCC G GCCAGUGC 7065 GCACUGGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GGCCCUAC 7619 1414 UAGGGCCG G CCAGUGCA 5959 UGCACUGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CGGCCCUA 7620 1418 GCCGGCCA G UGCAAGGC 5960 GCCUUGCA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGGCCGGC 7621 1420 CGGCCAGU G CAAGGCCA 5961 UGGCCUUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACUGGCCG 7622 1424 CAGUGCAA G GCCACUGC 7066 GCAGUGGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUGCACUG 7623 1425 AGUGCAAG G CCACUGCC 5962 GGCAGUGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUUGCACU 7624 1431 AGGCCACU G CCUGCCCG 5963 CGGGCAGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGUGGCCU 7625 1435 CACUGCCU G CCCGAGGA 5964 UCCUCGGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGGCAGUG 7626 1439 GCCUGCCC G AGGACGUG 7067 CACGUCCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GGGCAGGC 7627 1441 CUGCCCGA G GACGUGCC 7068 GGCACGUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCGGGCAG 7628 1442 UGCCCGAG G ACGUGCCC 7069 GGGCACGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUCGGGCA 7629 1445 CCGAGGAC G UGCCCGGG 5965 CCCGGGCA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GUCCUCGG 7630 1447 GAGGACGU G CCCGGGAC 5966 GUCCCGGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACGUCCUC 7631 1451 ACGUGCCC G GGACCGUG 7070 CACGGUCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GGGCACGU 7632 1452 CGUGCCCG G GACCGUGC 7071 GCACGGUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CGGGCACG 7633 1453 GUGCCCGG G ACCGUGCA 7072 UGCACGGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCGGGCAC 7634 1457 CCGGGACC G UGCAGUCU 5967 AGACUGCA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GGUCCCGG 7635 1459 GGGACCGU G CAGUCUGC 5968 GCAGACUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACGGUCCC 7636 1462 ACCGUGCA G UCUGCGCU 5969 AGCGCAGA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGCACGGU 7637 1466 UGCAGUCU G CGCUUUCC 5970 GGAAAGCG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGACUGCA 7638 1468 CAGUCUGC G CUUUCCUC 5971 GAGGAAAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GCAGACUG 7639 1481 CCUCUCCC G CCUGCCUA 5972 UAGGCAGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GGGAGAGG 7640 1485 UCCCGCCU G CCUAGCCC 5973 GGGCUAGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG

AGGCGGGA 7641 1490 CCUGCCUA G CCCAGGAU 5974 AUCCUGGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UAGGCAGG 7642 1495 CUAGCCCA G GAUGAAGG 7073 CCUUCAUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGGGCUAG 7643 1496 UAGCCCAG G AUGAAGGG 7074 CCCUUCAU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUGGGCUA 7644 1499 CCCAGGAU G AAGGGCUG 7075 CAGCCCUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUCCUGGG 7645 1502 AGGAUGAA G GGCUGGGU 7076 ACCCAGCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUCAUCCU 7646 1503 GGAUGAAG G GCUGGGUG 7077 CACCCAGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUUCAUCC 7647 1504 GAUGAAGG G CUGGGUGG 5975 CCACCCAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCUUCAUC 7648 1507 GAAGGGCU G GGUGGCCA 7078 UGGCCACC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGCCCUUC 7649 1508 AAGGGCUG G GUGGCCAC 7079 GUGGCCAC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAGCCCUU 7650 1509 AGGGCUGG G UGGCCACA 5976 UGUGGCCA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCAGCCCU 7651 1511 GGCUGGGU G GCCACAAC 7080 GUUGUGGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACCCAGCC 7652 1512 GCUGGGUG G CCACAACU 5977 AGUUGUGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CACCCAGC 7653 1521 CCACAACU G GGAUGCCA 7081 UGGCAUCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGUUGUGG 7654 1522 CACAACUG G GAUGCCAC 7082 GUGGCAUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAGUUGUG 7655 1523 ACAACUGG G AUGCCACC 7083 GGUGGCAU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCAGUUGU 7656 1526 ACUGGGAU G CCACCUGG 5978 CCAGGUGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUCCCAGU 7657 1533 UGCCACCU G GAGCCCCA 7084 UGGGGCUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGGUGGCA 7658 1534 GCCACCUG G AGCCCCAC 7085 GUGGGGCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAGGUGGC 7659 1536 CACCUGGA G CCCCACCC 5979 GGGUGGGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCCAGGUG 7660 1546 CCCACCCA G GAGCUGGC 7086 GCCAGCUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGGGUGGG 7661 1547 CCACCCAG G AGCUGGCC 7087 GGCCAGCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUGGGUGG 7662 1549 ACCCAGGA G CUGGCCGC 5980 GCGGCCAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCCUGGGU 7663 1552 CAGGAGCU 0 GCCGCGGC 7088 GCCGCGGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGCUCCUG 7664 1553 AGGAGCUG G CCGCGGCA 5981 UGCCGCGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAGCUCCU 7665 1556 AGCUGGCC G CGGCACCU 5982 AGGUGCCG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GGCCAGCU 7666 1558 CUGGCCGC G GCACCUUA 7089 UAAGGUGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GCGGCCAG 7667 1559 UGGCCGCG G CACCUUAC 5983 GUAAGGUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CGCGGCCA 7668 1568 CACCUUAC G CUUCAGCU 5984 AGCUGAAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GUAAGGUG 7669 1574 ACGCUUCA G CUGUUGAU 5985 AUCAACAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGAAGCGU 7670 1577 CUUCAGCU G UUGAUCCG 5986 CGGAUCAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGCUGAAG 7671 1580 CAGCUGUU G AUCCGCUG 7090 CAGCGGAU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AACAGCUG 7672 1585 GUUGAUCC G CUGGUCCC 5987 GGGACCAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GGAUCAAC 7673 1588 GAUCCGCU G GUCCCCUC 7091 GAGGGGAC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGCGGAUC 7674 1589 AUCCGCUG G UCCCCUCU 5988 AGAGGGGA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAGCGGAU 7675 1601 CCUCUUUU G GGGUAGAU 7092 AUCUACCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAAAGAGG 7676 1602 CUCUUUUG G GGUAGAUG 7093 CAUCUACC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAAAAGAG 7677 1603 UCUUUUGG G GUAGAUGC 7094 GCAUCUAC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCAAAAGA 7678 1604 CUUUUGGG G UAGAUGCG 5989 CGCAUCUA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCCAAAAG 7679 1607 UUGGGGUA G AUGCGGCC 7095 GGCCGCAU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UACCCCAA 7680 1610 GGGUAGAU G CGGCCCCG 5990 CGGGGCCG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUCUACCC 7681 1612 GUAGAUGC G GCCCCGAU 7096 AUCGGGGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GCAUCUAC 7682 1613 UAGAUGCG G CCCCGAUC 5991 GAUCGGGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CGCAUCUA 7683 1618 GCGGCCCC G AUCAGGCC 7097 GGCCUGAU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GGGGCCGC 7684 1623 CCCGAUCA G GCCUGACU 7098 AGUCAGCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGAUCGGG 7685 1624 CCGAUCAG G CCUGACUC 5992 GAGUCAGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUGAUCGG 7686 1628 UCAGGCCU G ACUCGCUG 7099 CAGCGAGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGGCCUGA 7687 1633 CCUGACUC G CUGCUCUU 5993 AAGAGCAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GAGUCAGG 7688 1636 GACUCGCU G CUCUUUUU 5994 AAAAAGAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGCGAGUC 7689 1645 CUCUUUUU G UUCCCUUC 5995 GAAGGGAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAAAAGAG 7690 1655 UCCCUUCU G UCUGCUCG 5996 CGAGCAGA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGAAGGGA 7691 1659 UUCUGUCU G CUCGAACC 5997 GGUUCGAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGACAGAA 7692 1663 GUCUGCUC G AACCACUU 7100 AAGUGGUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GAGCAGAC 7693 1672 AACCACUU G CCUCGGGC 5998 GCCCGAGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAGUGGUU 7694 1677 CUUGCCUC G GGCUAAUC 7101 GAUUAGCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GAGGCAAG 7695 1678 UUGCCUCG G GCUAAUCC 7102 GGAUUAGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CGAGGCAA 7696 1679 UGCCUCGG G CUAAUCCC 5999 GGGAUUAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCGAGGCA 7697 1705 CUCCACCC G GCACUGGG 7103 CCCAGUGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GGGUGGAG 7698 1706 UCCACCCG G CACUGGGG 6000 CCCCAGUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CGGGUGGA 7699 1711 CCGGCACU G GGGAAGUC 7104 GACUUCCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGUGCCGG 7700 1712 CGGCACUG G GGAAGUCA 7105 UGACUUCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAGUGCCG 7701 1713 GGCACUGG G GAAGUCAA 7106 UUGACUUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCAGUGCC 7702 1714 GCACUGGG G AAGUCAAG 7107 CUUGACUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCCAGUGC 7703 1717 CUGGGGAA G UCAAGAAU 6001 AUUCUUGA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUCCCCAG 7704 1722 GAAGUCAA G AAUGGGGC 7108 GCCCCAUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUGACUUC 7705 1726 UCAAGAAU G GGGCCUGG 7109 CCAGGCCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUUCUUGA 7706 1727 CAAGAAUG G GGCCUGGG 7110 CCCAGGCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAUUCUUG 7707 1728 AAGAAUGG G GCCUGGGG 7111 CCCCAGGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCAUUCUU 7708 1729 AGAAUGGG G CCUGGGGC 6002 GCCCCAGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCCAUUCU 7709 1733 UGGGGCCU G GGGCUCUC 7112 GAGAGCCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGGCCCCA 7710 1734 GGGGCCUG G GGCUCUCA 7113 UGAGAGCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAGGCCCC 7711 1735 GGGCCUGG G GCUCUCAG 7114 CUGAGAGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCAGGCCC 7712 1736 GGCCUGGG G CUCUCAGG 6003 CCUGAGAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCCAGGCC 7713 1743 GGCUCUCA G GGAGAACU 7115 AGUUCUCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGAGAGCC 7714 1744 GCUCUCAG G GAGAACUG 7116 CAGUUCUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUGAGAGC 7715 1745 CUCUCAGG G AGAACUGC 7117 GCAGUUCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCUGAGAG 7716 1747 CUCAGGGA G AACUGCUU 7118 AAGCAGUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCCCUGAG 7717 1752 GGAGAACU G CUUCCCCU 6004 AGGGGAAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGUUCUCC 7718 1761 CUUCCCCU G GCAGAGCU 7119 AGCUCUGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGGGGAAG 7719 1762 UUCCCCUG G CAGAGCUG 6005 CAGCUCUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAGGGGAA 7720 1765 CCCUGGCA G AGCUGGGU 7120 ACCCAGCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGCCAGGG 7721 1767 CUGGCAGA G CUGGGUGG 6006 CCACCCAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCUGCCAG 7722 1770 GCAGAGCU G GGUGGCAG 7121 CUGCCACC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGCUCUGC 7723 1771 CAGAGCUG G GUGGCAGC 7122 GCUGCCAC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CACCUCUG 7724

1772 AGAGCUGG G UGGCAGCU 6007 AGCUGCCA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCAGCUCU 7725 1774 AGCUGGGU G GCAGCUCU 7123 AGAGCUGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACCCAGCU 7726 1775 GCUGGGUG G CAGCUCUU 6008 AAGAGCUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CACCCAGC 7727 1778 GGGUGGCA G CUCUUCCU 6009 AGGAAGAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGCCACCC 7728 1793 CUCCCACC G GACACCGA 7124 UCGGUGUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GGUGGGAG 7729 1794 UCCCACCG G ACACCGAC 7125 GUCGGUGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CGGUGGGA 7730 1800 CGGACACC G ACCCGCCC 7126 GGGCGGGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GGUGUCCG 7731 1805 ACCGACCC G CCCGCCGC 6010 GCGGCGGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GGGUCGGU 7732 1809 ACCCGCCC G CCGCUGUG 6011 CACAGCGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GGGCGGGU 7733 1812 CGCCCGCC G CUGUGCCC 6012 GGGCACAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GGCGGGCG 7734 1815 CCGCCGCU G UGCCCUGG 6013 CCAGGGCA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGCGGCGG 7735 1817 GCCGCUGU G CCCUGGGA 6014 UCCCAGGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACAGCGGC 7736 1822 UGUGCCCU G GGAGUGCU 7127 AGCACUCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGGGCACA 7737 1823 GUGCCCUG G GAGUGCUG 7128 CAGCACUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAGGGCAC 7738 1824 UGCCCUGG G AGUGCUGC 7129 GCAGCACU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCAGGGCA 7739 1826 CCCUGGGA G UGCUGCCC 6015 GGGCAGCA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCCCAGGG 7740 1828 CUGGGAGU G CUGCCCUC 6016 GAGGGCAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACUCCCAG 7741 1831 GGAGUGCU G CCCUCUUA 6017 UAAGAGGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGCACUCC 7742 1844 CUUACCAU G CACACGGG 6018 CCCGUGUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUGGUAAG 7743 1850 AUGCACAC G GGUGCUCU 7130 AGAGCACC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GUGUGCAU 7744 1851 UGCACACG G GUGCUCUC 7131 GAGAGCAC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CGUGUGCA 7745 1852 GCACACGG G UGCUCUCC 6019 GGAGAGCA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCGUGUGC 7746 1854 ACACGGGU G CUCUCCUU 6020 AAGGAGAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACCCGUGU 7747 1865 CUCCUUUU G GGCUGCAU 7132 AUGCAGCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAAAGGAG 7748 1866 UCCUUUUG G GCUGCAUG 7133 CAUGCAGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGCG CAAAAGGA 7749 1867 CCUUUUGG G CUGCAUGC 6021 GCAUGCAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCAAAAGG 7750 1870 UUUGGGCU G CAUGCUAU 6022 AUAGCAUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGCCCAAA 7751 1874 GGCUGCAU G CUAUUCCA 6023 UGGAAUAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUGCAGCC 7752 1887 UCCAUUUU G CAGCCAGA 6024 UCUGGCUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAAAUGGA 7753 1890 AUUUUGCA G CCAGACCG 6025 CGGUCUGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGCAAAAU 7754 1894 UGCAGCCA G ACCGAUGU 7134 ACAUCGGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGGCUGCA 7755 1898 GCCAGACC G AUGUGUAU 7135 AUACACAU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GGUCUGGC 7756 1901 AGACCGAU G UGUAUUUA 6026 UAAAUACA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUCGGUCU 7757 1903 ACCGAUGU G UAUUUAAC 6027 GUUAAAUA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACAUCGGU 7758 1914 UUUAACCA G UCACUAUU 6028 AAUAGUGA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGGUUAAA 7759 1923 UCACUAUU G AUGGACAU 7136 AUGUCCAU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAUAGUGA 7760 1926 CUAUUGAU G GACAUUUG 7137 CAAAUGUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUCAAUAG 7761 1927 UAUUGAUG G ACAUUUGG 7138 CCAAAUGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAUCAAUA 7762 1934 GGACAUUU G GGUUGUUU 7139 AAACAACC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAAUGUCC 7763 1935 GACAUUUG G GUUGUUUC 7140 GAAACAAC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAAAUGUC 7764 1936 ACAUUUGG G UUGUUUCC 6029 GGAAACAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCAAAUGU 7765 1939 UUUGGGUU G UUUCCCAU 6030 AUGGGAAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AACCCAAA 7766 1954 AUCUUUUU G UUACCAUA 6031 UAUGGUAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAAAAGAU 7767 1969 UAAAUAAU G GCAUAGUA 7141 UACUAUGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUUAUUUA 7768 1970 AAAUAAUG G CAUAGUAA 6032 UUACUAUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAUUAUUU 7769 1975 AUGGCAUA G UAAAAAAA 6033 UUUUUUUA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UAUGCCAU 7770 Input Sequence = NM_003639. Cut Site = G/. Arm Length = 8. Core Sequence GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG NM_003639 (Homo sapiens inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase (IKBKG), mRNA.; 1994 bp)

[0270] TABLE-US-00008 TABLE VIII Human PKR Hammerhead and Substrate Sequence Seq Seq Pos Substrate ID Hammerhead ID 20 GGCGCAGU U UGCUCAUA 1 UAUGAGCA CUGAUGAGGCCGUUAGGCCGAA ACUGCGCC 632 21 GCGCAGUU U GCUCAUAC 2 GUAUGAGC CUGAUGAGGCCGUUAGGCCGAA AACUGCGC 633 25 AGUUUGCU C AUACUUUG 3 CAAAGUAU CUGAUGAGGCCGUUAGGCCGAA AGCAAACU 634 28 UUGCUCAU A CUUUGUGA 4 UCACAAAG CUGAUGAGGCCGUUAGGCCGAA AUGAGCAA 635 31 CUCAUACU U UGUGACUU 5 AAGUCACA CUGAUGAGGCCGUUAGGCCGAA AGUAUGAG 636 32 UCAUACUU U GUGACUUG 6 CAAGUCAC CUGAUGAGGCCGUUAGGCCGAA AAGUAUGA 637 39 UUGUGACU U GCGGUCAC 7 GUGACCGC CUGAUGAGGCCGUUAGGCCGAA AGUCACAA 638 45 CUUGCGGU C ACAGUGGC 8 GCCACUGU CUGAUGAGGCCGUUAGGCCGAA ACCGCAAG 639 56 AGUGGCAU U CAGCUCCA 9 UGGAGCUG CUGAUGAGGCCGUUAGGCCGAA AUGCCACU 640 57 GUGGCAUU C AGCUCCAC 10 GUGGAGCU CUGAUGAGGCCGUUAGGCCGAA AAUGCCAC 641 62 AUUCAGCU C CACACUUG 11 CAAGUGUG CUGAUGAGGCCGUUAGGCCGAA AGCUGAAU 642 69 UCCACACU U GGUAGAAC 12 GUUCUACC CUGAUGAGGCCGUUAGGCCGAA AGUGUGGA 643 73 CACUUGGU A GAACCACA 13 UGUGGUUC CUGAUGAGGCCGUUAGGCCGAA ACCAAGUG 644 96 ACAAGCAU A GAAACAUC 14 GAUGUUUC CUGAUGAGGCCGUUAGGCCGAA AUGCUUGU 645 104 AGAAACAU C CUAAACAA 15 UUGUUUAG CUGAUGAGGCCGUUAGGCCGAA AUGUUUCU 646 107 AACAUCCU A AACAAUCU 16 AGAUUGUU CUGAUGAGGCCGUUAGGCCGAA AGGAUGUU 647 114 UAAACAAU C UUCAUCGA 17 UCGAUGAA CUGAUGAGGCCGUUAGGCCGAA AUUGUUUA 648 116 AACAAUCU U CAUCGAGG 18 CCUCGAUG CUGAUGAGGCCGUUAGGCCGAA AGAUUGUU 649 117 ACAAUCUU C AUCGAGGC 19 GCCUCGAU CUGAUGAGGCCGUUAGGCCGAA AAGAUUGU 650 120 AUCUUCAU C GAGGCAUC 20 GAUGCCUC CUGAUGAGGCCGUUAGGCCGAA AUGAAGAU 651 128 CGAGGCAU C GAGGUCCA 21 UGGACCUC CUGAUGAGGCCGUUAGGCCGAA AUGCCUCG 652 134 AUCGAGGU C CAUCCCAA 22 UUGGGAUG CUGAUGAGGCCGUUAGGCCGAA ACCUCGAU 653 138 AGGUCCAU C CCAAUAAA 23 UUUAUUGG CUGAUGAGGCCGUUAGGCCGAA AUGGACCU 654 144 AUCCCAAU A AAAAUCAG 24 CUGAUUUU CUGAUGAGGCCGUUAGGCCGAA AUUGGGAU 655 150 AUAAAAAU C AGGAGACC 25 GGUCUCCU CUGAUGAGGCCGUUAGGCCGAA AUUUUUAU 656 165 CCCUGGCU A UCAUAGAC 26 GUCUAUGA CUGAUGAGGCCGUUAGGCCGAA AGCCAGGG 657 167 CUGGCUAU C AUAGACCU 27 AGGUCUAU CUGAUGAGGCCGUUAGGCCGAA AUAGCCAG 658 170 GCUAUCAU A GACCUUAG 28 CUAAGGUC CUGAUGAGGCCGUUAGGCCGAA AUGAUAGC 659 176 AUAGACCU U AGUCUUCG 29 CGAAGACU CUGAUGAGGCCGUUAGGCCGAA AGGUCUAU 660 177 UAGACCUU A GUCUUCGC 30 GCGAAGAC CUGAUGAGGCCGUUAGGCCGAA AAGGUCUA 661 180 ACCUUAGU C UUCGCUGG 31 CCAGCGAA CUGAUGAGGCCGUUAGGCCGAA ACUAAGGU 662 182 CUUAGUCU U CGCUGGUA 32 UACCAGCG CUGAUGAGGCCGUUAGGCCGAA AGACUAAG 663 183 UUAGUCUU C GCUGGUAU 33 AUACCAGC CUGAUGAGGCCGUUAGGCCGAA AAGACUAA 664 190 UCGCUGGU A UACUCGCU 34 AGCGAGUA CUGAUGAGGCCGUUAGGCCGAA ACCAGCGA 665 192 GCUGGUAU A CUCGCUGU 35 ACAGCGAG CUGAUGAGGCCGUUAGGCCGAA AUACCAGC 666 195 GGUAUACU C GCUGUCUG 36 CAGACAGC CUGAUGAGGCCGUUAGGCCGAA AGUAUACC 667 201 CUCGCUGU C UGUCAACC 37 GGUUGACA CUGAUGAGGCCGUUAGGCCGAA ACAGCGAG 668 205 CUGUCUGU C AACCAGCG 38 CGCUGGUU CUGAUGAGGCCGUUAGGCCGAA ACAGACAG 669 216 CCAGCGGU U GACUUUUU 39 AAAAAGUC CUGAUGAGGCCGUUAGGCCGAA ACCGCUGG 670 221 GGUUGACU U UUUUUAAG 40 CUUAAAAA CUGAUGAGGCCGUUAGGCCGAA AGUCAACC 671 222 GUUGACUU U UUUUAAGC 41 GCUUAAAA CUGAUGAGGCCGUUAGGCCGAA AAGUCAAC 672 223 UUGACUUU U UUUAAGCC 42 GGCUUAAA CUGAUGAGGCCGUUAGGCCGAA AAAGUCAA 673 224 UGACUUUU U UUAAGCCU 43 AGGCUUAA CUGAUGAGGCCGUUAGGCCGAA AAAAGUCA 674 225 GACUUUUU U UAAGCCUU 44 AAGGCUUA CUGAUGAGGCCGUUAGGCCGAA AAAAAGUC 675 226 ACUUUUUU U AAGCCUUC 45 GAAGGCUU CUGAUGAGGCCGUUAGGCCGAA AAAAAAGU 676 227 CUUUUUUU A AGCCUUCU 46 AGAAGGCU CUGAUGAGGCCGUUAGGCCGAA AAAAAAAG 677 233 UUAAGCCU U CUUUUUUC 47 GAAAAAAG CUGAUGAGGCCGUUAGGCCGAA AGGCUUAA 678 234 UAAGCCUU C UUUUUUCU 48 AGAAAAAA CUGAUGAGGCCGUUAGGCCGAA AAGGCUUA 679 236 AGCCUUCU U UUUUCUCU 49 AGAGAAAA CUGAUGAGGCCGUUAGGCCGAA AGAAGGCU 680 237 GCCUUCUU U UUUCUCUU 50 AAGAGAAA CUGAUGAGGCCGUUAGGCCGAA AAGAAGGC 681 238 CCUUCUUU U UUCUCUUU 51 AAAGAGAA CUGAUGAGGCCGUUAGGCCGAA AAAGAAGG 682 239 CUUCUUUU U UCUCUUUU 52 AAAAGAGA CUGAUGAGGCCGUUAGGCCGAA AAAAGAAG 683 240 UUCUUUUU U CUCUUUUA 53 UAAAAGAG CUGAUGAGGCCGUUAGGCCGAA AAAAAGAA 684 241 UCUUUUUU C UCUUUUAC 54 GUAAAAGA CUGAUGAGGCCGUUAGGCCGAA AAAAAAGA 685 243 UUUUUUCU C UUUUACCA 55 UGGUAAAA CUGAUGAGGCCGUUAGGCCGAA AGAAAAAA 686 245 UUUUCUCU U UUACCAGU 56 ACUGGUAA CUGAUGAGGCCGUUAGGCCGAA AGAGAAAA 687 246 UUUCUCUU U UACCAGUU 57 AACUGGUA CUGAUGAGGCCGUUAGGCCGAA AAGAGAAA 688 247 UUCUCUUU U ACCAGUUU 58 AAACUGGU CUGAUGAGGCCGUUAGGCCGAA AAAGAGAA 689 248 UCUCUUUU A CCAGUUUC 59 GAAACUGG CUGAUGAGGCCGUUAGGCCGAA AAAAGAGA 690 254 UUACCAGU U UCUGGAGC 60 GCUCCAGA CUGAUGAGGCCGUUAGGCCGAA ACUGGUAA 691 255 UACCAGUU U CUGGAGCA 61 UGCUCCAG CUGAUGAGGCCGUUAGGCCGAA AACUGGUA 692 256 ACCAGUUU C UGGAGCAA 62 UUGCUCCA CUGAUGAGGCCGUUAGGCCGAA AAACUGGU 693 267 GAGCAAAU U CAGUUUGC 63 GCAAACUG CUGAUGAGGCCGUUAGGCCGAA AUUUGCUC 694 268 AGCAAAUU C AGUUUGCC 64 GGCAAACU CUGAUGAGGCCGUUAGGCCGAA AAUUUGCU 695 272 AAUUCAGU U UGCCUUCC 65 GGAAGGCA CUGAUGAGGCCGUUAGGCCGAA ACUGAAUU 696 273 AUUCAGUU U GCCUUCCU 66 AGGAAGGC CUGAUGAGGCCGUUAGGCCGAA AACUGAAU 697 278 GUUUGCCU U CCUGGAUU 67 AAUCCAGG CUGAUGAGGCCGUUAGGCCGAA AGGCAAAC 698 279 UUUGCCUU C CUGGAUUU 68 AAAUCCAG CUGAUGAGGCCGUUAGGCCGAA AAGGCAAA 699 286 UCCUGGAU U UGUAAAUU 69 AAUUUACA CUGAUGAGGCCGUUAGGCCGAA AUCCAGGA 700 287 CCUGGAUU U GUAAAUUG 70 CAAUUUAC CUGAUGAGGCCGUUAGGCCGAA AAUCCAGG 701 290 GGAUUUGU A AAUUGUAA 71 UUACAAUU CUGAUGAGGCCGUUAGGCCGAA ACAAAUCC 702 294 UUGUAAAU U GUAAUGAC 72 GUCAUUAC CUGAUGAGGCCGUUAGGCCGAA AUUUACAA 703 297 UAAAUUGU A AUGACCUC 73 GAGGUCAU CUGAUGAGGCCGUUAGGCCGAA ACAAUUUA 704 305 AAUGACCU C AAAACUUU 74 AAAGUUUU CUGAUGAGGCCGUUAGGCCGAA AGGUCAUU 705 312 UCAAAACU U UAGCAGUU 75 AACUGCUA CUGAUGAGGCCGUUAGGCCGAA AGUUUUGA 706 313 CAAAACUU U AGCAGUUC 76 GAACUGCU CUGAUGAGGCCGUUAGGCCGAA AAGUUUUG 707 314 AAAACUUU A GCAGUUCU 77 AGAACUGC CUGAUGAGGCCGUUAGGCCGAA AAAGUUUU 708 320 UUAGCAGU U CUUCCAUC 78 GAUGGAAG CUGAUGAGGCCGUUAGGCCGAA ACUGCUAA 709 321 UAGCAGUU C UUCCAUCU 79 AGAUGGAA CUGAUGAGGCCGUUAGGCCGAA AACUGCUA 710 323 GCAGUUCU U CCAUCUGA 80 UCAGAUGG CUGAUGAGGCCGUUAGGCCGAA AGAACUGC 711 324 CAGUUCUU C CAUCUGAC 81 GUCAGAUG CUGAUGAGGCCGUUAGGCCGAA AAGAACUG 712 328 UCUUCCAU C UGACUCAG 82 CUGAGUCA CUGAUGAGGCCGUUAGGCCGAA AUGGAAGA 713 334 AUCUGACU C AGGUUUGC 83 GCAAACCU CUGAUGAGGCCGUUAGGCCGAA AGUCAGAU 714 339 ACUCAGGU U UGCUUCUC 84 GAGAAGCA CUGAUGAGGCCGUUAGGCCGAA ACCUGAGU 715 340 CUCAGGUU U GCUUCUCU 85 AGAGAAGC CUGAUGAGGCCGUUAGGCCGAA AACCUGAG 716 344 GGUUUGCU U CUCUGGCG 86 CGCCAGAG CUGAUGAGGCCGUUAGGCCGAA AGCAAACC 717 345 GUUUGCUU C UCUGGCGG 87 CCGCCAGA CUGAUGAGGCCGUUAGGCCGAA AAGCAAAC 718 347 UUGCUUCU C UGGCGGUC 88 GACCGCCA CUGAUGAGGCCGUUAGGCCGAA AGAAGCAA 719 355 CUGGCGGU C UUCAGAAU 89 AUUCUGAA CUGAUGAGGCCGUUAGGCCGAA ACCGCCAG 720 357 GGCGGUCU U CAGAAUCA 90 UGAUUCUG CUGAUGAGGCCGUUAGGCCGAA AGACCGCC 721 358 GCGGUCUU C AGAAUCAA 91 UUGAUUCU CUGAUGAGGCCGUUAGGCCGAA AAGACCGC 722 364 UUCAGAAU C AACAUCCA 92 UGGAUGUU CUGAUGAGGCCGUUAGGCCGAA AUUCUGAA 723 370 AUCAACAU C CACACUUC 93 GAAGUGUG CUGAUGAGGCCGUUAGGCCGAA AUGUUGAU 724 377 UCCACACU U CCGUGAUU 94 AAUCACGG CUGAUGAGGCCGUUAGGCCGAA AGUGUGGA 725 378 CCACACUU C CGUGAUUA 95 UAAUCACG CUGAUGAGGCCGUUAGGCCGAA AAGUGUGG 726 385 UCCGUGAU U AUCUGCGU 96 ACGCAGAU CUGAUGAGGCCGUUAGGCCGAA AUCACGGA 727 386 CCGUGAUU A UCUGCGUG 97 CACGCAGA CUGAUGAGGCCGUUAGGCCGAA AAUCACGG 728 388 GUGAUUAU C UGCGUGCA 98 UGCACGCA CUGAUGAGGCCGUUAGGCCGAA AUAAUCAC 729 398 GCGUGCAU U UUGGACAA 99 UUGUCCAA CUGAUGAGGCCGUUAGGCCGAA AUGCACGC 730 399 CGUGCAUU U UGGACAAA 100 UUUGUCCA CUGAUGAGGCCGUUAGGCCGAA AAUGCACG 731 400 GUGCAUUU U GGACAAAG 101 CUUUGUCC CUGAUGAGGCCGUUAGGCCGAA AAAUGCAC 732 411 ACAAAGCU U CCAACCAG 102 CUGGUUGG CUGAUGAGGCCGUUAGGCCGAA AGCUUUGU 733 412 CAAAGCUU C CAACCAGG 103 CCUGGUUG CUGAUGAGGCCGUUAGGCCGAA AAGCUUUG 734 423 ACCAGGAU A CGGGAAGA 104 UCUUCCCG CUGAUGAGGCCGUUAGGCCGAA AUCCUGGU 735 448 CUGGUGAU C UUUCAGCA 105 UGCUGAAA CUGAUGAGGCCGUUAGGCCGAA AUCACCAG 736 450 GGUGAUCU U UCAGCAGG 106 CCUGCUGA CUGAUGAGGCCGUUAGGCCGAA AGAUCACC 737 451 GUGAUCUU U CAGCAGGU 107 ACCUGCUG CUGAUGAGGCCGUUAGGCCGAA AAGAUCAC 738 452 UGAUCUUU C AGCAGGUU 108 AACCUGCU CUGAUGAGGCCGUUAGGCCGAA AAAGAUCA 739 460 CAGCAGGU U UCUUCAUG 109 CAUGAAGA CUGAUGAGGCCGUUAGGCCGAA ACCUGCUG 740 461 AGCAGGUU U CUUCAUGG 110 CCAUGAAG CUGAUGAGGCCGUUAGGCCGAA AACCUGCU 741 462 GCAGGUUU C UUCAUGGA 111 UCCAUGAA CUGAUGAGGCCGUUAGGCCGAA AAACCUGC 742 464 AGGUUUCU U CAUGGAGG 112 CCUCCAUG CUGAUGAGGCCGUUAGGCCGAA AGAAACCU 743 465 GGUUUCUU C AUGGAGGA 113 UCCUCCAU CUGAUGAGGCCGUUAGGCCGAA AAGAAACC 744 477 GAGGAACU U AAUACAUA 114 UAUGUAUU CUGAUGAGGCCGUUAGGCCGAA AGUUCCUC 745 478 AGGAACUU A AUACAUAC 115 GUAUGUAU CUGAUGAGGCCGUUAGGCCGAA AAGUUCCU 746 481 AACUUAAU A CAUACCGU 116 ACGGUAUG CUGAUGAGGCCGUUAGGCCGAA AUUAAGUU 747 485 UAAUACAU A CCGUCAGA 117 UCUGACGG CUGAUGAGGCCGUUAGGCCGAA AUGUAUUA 748 490 CAUACCGU C AGAAGCAG 118 CUGCUUCU CUGAUGAGGCCGUUAGGCCGAA ACGGUAUG 749 504 CAGGGAGU A GUACUUAA 119 UUAAGUAC CUGAUGAGGCCGUUAGGCCGAA ACUCCCUG 750 507 GGAGUAGU A CUUAAAUA 120 UAUUUAAG CUGAUGAGGCCGUUAGGCCGAA ACUACUCC 751 510 GUAGUACU U AAAUAUCA 121 UGAUAUUU CUGAUGAGGCCGUUAGGCCGAA AGUACUAC 752 511 UAGUACUU A AAUAUCAA 122 UUGAUAUU CUGAUGAGGCCGUUAGGCCGAA AAGUACUA 753

515 ACUUAAAU A UCAAGAAC 123 GUUCUUGA CUGAUGAGGCCGUUAGGCCGAA AUUUAAGU 754 517 UUAAAUAU C AAGAACUG 124 CAGUUCUU CUGAUGAGGCCGUUAGGCCGAA AUAUUUAA 755 529 AACUGCCU A AUUCAGGA 125 UCCUGAAU CUGAUGAGGCCGUUAGGCCGAA AGGCAGUU 756 532 UGCCUAAU U CAGGACCU 126 AGGUCCUG CUGAUGAGGCCGUUAGGCCGAA AUUAGGCA 757 533 GCCUAAUU C AGGACCUC 127 GAGGUCCU CUGAUGAGGCCGUUAGGCCGAA AAUUAGGC 758 541 CAGGACCU C CACAUGAU 128 AUCAUGUG CUGAUGAGGCCGUUAGGCCGAA AGGUCCUG 759 550 CACAUGAU A GGAGGUUU 129 AAACCUCC CUGAUGAGGCCGUUAGGCCGAA AUCAUGUG 760 557 UAGGAGGU U UACAUUUC 130 GAAAUGUA CUGAUGAGGCCGUUAGGCCGAA ACCUCCUA 761 558 AGGAGGUU U ACAUUUCA 131 UGAAAUGU CUGAUGAGGCCGUUAGGCCGAA AACCUCCU 762 559 GGAGGUUU A CAUUUCAA 132 UUGAAAUG CUGAUGAGGCCGUUAGGCCGAA AAACCUCC 763 563 GUUUACAU U UCAAGUUA 133 UAACUUGA CUGAUGAGGCCGUUAGGCCGAA AUGUAAAC 764 564 UUUACAUU U CAAGUUAU 134 AUAACUUG CUGAUGAGGCCGUUAGGCCGAA AAUGUAAA 765 565 UUACAUUU C AAGUUAUA 135 UAUAACUU CUGAUGAGGCCGUUAGGCCGAA AAAUGUAA 766 570 UUUCAAGU U AUAAUAGA 136 UCUAUUAU CUGAUGAGGCCGUUAGGCCGAA ACUUGAAA 767 571 UUCAAGUU A UAAUAGAU 137 AUCUAUUA CUGAUGAGGCCGUUAGGCCGAA AACUUGAA 768 573 CAAGUUAU A AUAGAUGG 138 CCAUCUAU CUGAUGAGGCCGUUAGGCCGAA AUAACUUG 769 576 GUUAUAAU A GAUGGAAG 139 CUUCCAUC CUGAUGAGGCCGUUAGGCCGAA AUUAUAAC 770 590 AAGAGAAU U UCCAGAAG 140 CUUCUGGA CUGAUGAGGCCGUUAGGCCGAA AUUCUCUU 771 591 AGAGAAUU U CCAGAAGG 141 CCUUCUGG CUGAUGAGGCCGUUAGGCCGAA AAUUCUCU 772 592 GAGAAUUU C CAGAAGGU 142 ACCUUCUG CUGAUGAGGCCGUUAGGCCGAA AAAUUCUC 773 607 GUGAAGGU A GAUCAAAG 143 CUUUGAUC CUGAUGAGGCCGUUAGGCCGAA ACCUUCAC 774 611 AGGUAGAU C AAAGAAGG 144 CCUUCUUU CUGAUGAGGCCGUUAGGCCGAA AUCUACCU 775 644 AGCCAAAU U AGCUGUUG 145 CAACAGCU CUGAUGAGGCCGUUAGGCCGAA AUUUGGCU 776 645 GCCAAAUU A GCUGUUGA 146 UCAACAGC CUGAUGAGGCCGUUAGGCCGAA AAUUUGGC 777 651 UUAGCUGU U GAGAUACU 147 AGUAUCUC CUGAUGAGGCCGUUAGGCCGAA ACAGCUAA 778 657 GUUGAGAU A CUUAAUAA 148 UUAUUAAG CUGAUGAGGCCGUUAGGCCGAA AUCUCAAC 779 660 GAGAUACU U AAUAAGGA 149 UCCUUAUU CUGAUGAGGCCGUUAGGCCGAA AGUAUCUC 780 661 AGAUACUU A AUAAGGAA 150 UUCCUUAU CUGAUGAGGCCGUUAGGCCGAA AAGUAUCU 781 664 UACUUAAU A AGGAAAAG 151 CUUUUCCU CUGAUGAGGCCGUUAGGCCGAA AUUAAGUA 782 681 AAGGCAGU U AGUCCUUU 152 AAAGGACU CUGAUGAGGCCGUUAGGCCGAA ACUGCCUU 783 682 AGGCAGUU A GUCCUUUA 153 UAAAGGAC CUGAUGAGGCCGUUAGGCCGAA AACUGCCU 784 685 CAGUUAGU C CUUUAUUA 154 UAAUAAAG CUGAUGAGGCCGUUAGGCCGAA ACUAACUG 785 688 UUAGUCCU U UAUUAUUG 155 CAAUAAUA CUGAUGAGGCCGUUAGGCCGAA AGGACUAA 786 689 UAGUCCUU U AUUAUUGA 156 UCAAUAAU CUGAUGAGGCCGUUAGGCCGAA AAGGACUA 787 690 AGUCCUUU A UUAUUGAC 157 GUCAAUAA CUGAUGAGGCCGUUAGGCCGAA AAAGGACU 788 692 UCCUUUAU U AUUGACAA 158 UUGUCAAU CUGAUGAGGCCGUUAGGCCGAA AUAAAGGA 789 693 CCUUUAUU A UUGACAAC 159 GUUGUCAA CUGAUGAGGCCGUUAGGCCGAA AAUAAAGG 790 695 UUUAUUAU U GACAACAA 160 UUGUUGUC CUGAUGAGGCCGUUAGGCCGAA AUAAUAAA 791 709 CAACGAAU U CUUCAGAA 161 UUCUGAAG CUGAUGAGGCCGUUAGGCCGAA AUUCGUUG 792 710 AACGAAUU C UUCAGAAG 162 CUUCUGAA CUGAUGAGGCCGUUAGGCCGAA AAUUCGUU 793 712 CGAAUUCU U CAGAAGGA 163 UCCUUCUG CUGAUGAGGCCGUUAGGCCGAA AGAAUUCG 794 713 GAAUUCUU C AGAAGGAU 164 AUCCUUCU CUGAUGAGGCCGUUAGGCCGAA AAGAAUUC 795 722 AGAAGGAU U AUCCAUGG 165 CCAUGGAU CUGAUGAGGCCGUUAGGCCGAA AUCCUUCU 796 723 GAAGGAUU A UCCAUGGG 166 CCCAUGGA CUGAUGAGGCCGUUAGGCCGAA AAUCCUUC 797 725 AGGAUUAU C CAUGGGGA 167 UCCCCAUG CUGAUGAGGCCGUUAGGCCGAA AUAAUCCU 798 736 UGGGGAAU U ACAUAGGC 168 GCCUAUGU CUGAUGAGGCCGUUAGGCCGAA AUUCCCCA 799 737 GGGGAAUU A CAUAGGCC 169 GGCCUAUG CUGAUGAGGCCGUUAGGCCGAA AAUUCCCC 800 741 AAUUACAU A GGCCUUAU 170 AUAAGGCC CUGAUGAGGCCGUUAGGCCGAA AUGUAAUU 801 747 AUAGGCCU U AUCAAUAG 171 CUAUUGAU CUGAUGAGGCCGUUAGGCCGAA AGGCCUAU 802 748 UAGGCCUU A UCAAUAGA 172 UCUAUUGA CUGAUGAGGCCGUUAGGCCGAA AAGGCCUA 803 750 GGCCUUAU C AAUAGAAU 173 AUUCUAUU CUGAUGAGGCCGUUAGGCCGAA AUAAGGCC 804 754 UUAUCAAU A GAAUUGCC 174 GGCAAUUC CUGAUGAGGCCGUUAGGCCGAA AUUGAUAA 805 759 AAUAGAAU U GCCCAGAA 175 UUCUGGGC CUGAUGAGGCCGUUAGGCCGAA AUUCUAUU 806 777 AAAAGACU A ACUGUAAA 176 UUUACAGU CUGAUGAGGCCGUUAGGCCGAA AGUCUUUU 807 783 CUAACUGU A AAUUAUGA 177 UCAUAAUU CUGAUGAGGCCGUUAGGCCGAA ACAGUUAG 808 787 CUGUAAAU U AUGAACAG 178 CUGUUCAU CUGAUGAGGCCGUUAGGCCGAA AUUUACAG 809 788 UGUAAAUU A UGAACAGU 179 ACUGUUCA CUGAUGAGGCCGUUAGGCCGAA AAUUUACA 810 803 GUGUGCAU C GGGGGUGC 180 GCACCCCC CUGAUGAGGCCGUUAGGCCGAA AUGCACAC 811 827 AGAAGGAU U UCAUUAUA 181 UAUAAUGA CUGAUGAGGCCGUUAGGCCGAA AUCCUUCU 812 828 GAAGGAUU U CAUUAUAA 182 UUAUAAUG CUGAUGAGGCCGUUAGGCCGAA AAUCCUUC 813 829 AAGGAUUU C AUUAUAAA 183 UUUAUAAU CUGAUGAGGCCGUUAGGCCGAA AAAUCCUU 814 832 GAUUUCAU U AUAAAUGC 184 GCAUUUAU CUGAUGAGGCCGUUAGGCCGAA AUGAAAUC 815 833 AUUUCAUU A UAAAUGCA 185 UGCAUUUA CUGAUGAGGCCGUUAGGCCGAA AAUGAAAU 816 835 UUCAUUAU A AAUGCAAA 186 UUUGCAUU CUGAUGAGGCCGUUAGGCCGAA AUAAUGAA 817 860 GAAAGAAU A UAGUAUUG 187 CAAUACUA CUGAUGAGGCCGUUAGGCCGAA AUUCUUUC 818 862 AAGAAUAU A GUAUUGGU 188 ACCAAUAC CUGAUGAGGCCGUUAGGCCGAA AUAUUCUU 819 865 AAUAUAGU A UUGGUACA 189 UGUACCAA CUGAUGAGGCCGUUAGGCCGAA ACUAUAUU 820 867 UAUAGUAU U GGUACAGG 190 CCUGUACC CUGAUGAGGCCGUUAGGCCGAA AUACUAUA 821 871 GUAUUGGU A CAGGUUCU 191 AGAACCUG CUGAUGAGGCCGUUAGGCCGAA ACCAAUAC 822 877 GUACAGGU U CUACUAAA 192 UUUAGUAG CUGAUGAGGCCGUUAGGCCGAA ACCUGUAC 823 878 UACAGGUU C UACUAAAC 193 GUUUAGUA CUGAUGAGGCCGUUAGGCCGAA AACCUGUA 824 880 CAGGUUCU A CUAAACAG 194 CUGUUUAG CUGAUGAGGCCGUUAGGCCGAA AGAACCUG 825 883 GUUCUACU A AACAGGAA 195 UUCCUGUU CUGAUGAGGCCGUUAGGCCGAA AGUAGAAC 826 902 AAAACAAU U GGCCGCUA 196 UAGCGGCC CUGAUGAGGCCGUUAGGCCGAA AUUGUUUU 827 910 UGGCCGCU A AACUUGCA 197 UGCAAGUU CUGAUGAGGCCGUUAGGCCGAA AGCGGCCA 828 915 GCUAAACU U GCAUAUCU 198 AGAUAUGC CUGAUGAGGCCGUUAGGCCGAA AGUUUAGC 829 920 ACUUGCAU A UCUUCAGA 199 UCUGAAGA CUGAUGAGGCCGUUAGGCCGAA AUGCAAGU 830 922 UUGCAUAU C UUCAGAUA 200 UAUCUGAA CUGAUGAGGCCGUUAGGCCGAA AUAUGCAA 831 924 GCAUAUCU U CAGAUAUU 201 AAUAUCUG CUGAUGAGGCCGUUAGGCCGAA AGAUAUGC 832 925 CAUAUCUU C AGAUAUUA 202 UAAUAUCU CUGAUGAGGCCGUUAGGCCGAA AAGAUAUG 833 930 CUUCAGAU A UUAUCAGA 203 UCUGAUAA CUGAUGAGGCCGUUAGGCCGAA AUCUGAAG 834 932 UCAGAUAU U AUCAGAAG 204 CUUCUGAU CUGAUGAGGCCGUUAGGCCGAA AUAUCUGA 835 933 CAGAUAUU A UCAGAAGA 205 UCUUCUGA CUGAUGAGGCCGUUAGGCCGAA AAUAUCUG 836 935 GAUAUUAU C AGAAGAAA 206 UUUCUUCU CUGAUGAGGCCGUUAGGCCGAA AUAAUAUC 837 947 AGAAACCU C AGUGAAAU 207 AUUUCACU CUGAUGAGGCCGUUAGGCCGAA AGGUUUCU 838 956 AGUGAAAU C UGACUACC 208 GGUAGUCA CUGAUGAGGCCGUUAGGCCGAA AUUUCACU 839 962 AUCUGACU A CCUGUCCU 209 AGGACAGG CUGAUGAGGCCGUUAGGCCGAA AGUCAGAU 840 968 CUACCUGU C CUCUGGUU 210 AACCAGAG CUGAUGAGGCCGUUAGGCCGAA ACAGGUAG 841 971 CCUGUCCU C UGGUUCUU 211 AAGAACCA CUGAUGAGGCCGUUAGGCCGAA AGGACAGG 842 976 CCUCUGGU U CUUUUGCU 212 AGCAAAAG CUGAUGAGGCCGUUAGGCCGAA ACCAGAGG 843 977 CUCUGGUU C UUUUGCUA 213 UAGCAAAA CUGAUGAGGCCGUUAGGCCGAA AACCAGAG 844 979 CUGGUUCU U UUGCUACU 214 AGUAGCAA CUGAUGAGGCCGUUAGGCCGAA AGAACCAG 845 980 UGGUUCUU U UGCUACUA 215 UAGUAGCA CUGAUGAGGCCGUUAGGCCGAA AAGAACCA 846 981 GGUUCUUU U GCUACUAC 216 GUAGUAGC CUGAUGAGGCCGUUAGGCCGAA AAAGAACC 847 985 CUUUUGCU A CUACGUGU 217 ACACGUAG CUGAUGAGGCCGUUAGGCCGAA AGCAAAAG 848 988 UUGCUACU A CGUGUGAG 218 CUCACACG CUGAUGAGGCCGUUAGGCCGAA AGUAGCAA 849 998 GUGUGAGU C CCAAAGCA 219 UGCUUUGG CUGAUGAGGCCGUUAGGCCGAA ACUCACAC 850 1010 AAGCAACU C UUUAGUGA 220 UCACUAAA CUGAUGAGGCCGUUAGGCCGAA AGUUGCUU 851 1012 GCAACUCU U UAGUGACC 221 GGUCACUA CUGAUGAGGCCGUUAGGCCGAA AGAGUUGC 852 1013 CAACUCUU U AGUGACCA 222 UGGUCACU CUGAUGAGGCCGUUAGGCCGAA AAGAGUUG 853 1014 AACUCUUU A GUGACCAG 223 CUGGUCAC CUGAUGAGGCCGUUAGGCCGAA AAAGAGUU 854 1029 AGCACACU C GCUUCUGA 224 UCAGAAGC CUGAUGAGGCCGUUAGGCCGAA AGUGUGCU 855 1033 CACUCGCU U CUGAAUCA 225 UGAUUCAG CUGAUGAGGCCGUUAGGCCGAA AGCGAGUG 856 1034 ACUCGCUU C UGAAUCAU 226 AUGAUUCA CUGAUGAGGCCGUUAGGCCGAA AAGCGAGU 857 1040 UUCUGAAU C AUCAUCUG 227 CAGAUGAU CUGAUGAGGCCGUUAGGCCGAA AUUCAGAA 858 1043 UGAAUCAU C AUCUGAAG 228 CUUCAGAU CUGAUGAGGCCGUUAGGCCGAA AUGAUUCA 859 1046 AUCAUCAU C UGAAGGUG 229 CACCUUCA CUGAUGAGGCCGUUAGGCCGAA AUGAUGAU 860 1058 AGGUGACU U CUCAGCAG 230 CUGCUGAG CUGAUGAGGCCGUUAGGCCGAA AGUCACCU 861 1059 GGUGACUU C UCAGCAGA 231 UCUGCUGA CUGAUGAGGCCGUUAGGCCGAA AAGUCACC 862 1061 UGACUUCU C AGCAGAUA 232 UAUCUGCU CUGAUGAGGCCGUUAGGCCGAA AGAAGUCA 863 1069 CAGCAGAU A CAUCAGAG 233 CUCUGAUG CUGAUGAGGCCGUUAGGCCGAA AUCUGCUG 864 1073 AGAUACAU C AGAGAUAA 234 UUAUCUCU CUGAUGAGGCCGUUAGGCCGAA AUGUAUCU 865 1080 UCAGAGAU A AAUUCUAA 235 UUAGAAUU CUGAUGAGGCCGUUAGGCCGAA AUCUCUGA 866 1084 AGAUAAAU U CUAACAGU 236 ACUGUUAG CUGAUGAGGCCGUUAGGCCGAA AUUUAUCU 867 1085 GAUAAAUU C UAACAGUG 237 CACUGUUA CUGAUGAGGCCGUUAGGCCGAA AAUUUAUC 868 1087 UAAAUUCU A ACAGUGAC 238 GUCACUGU CUGAUGAGGCCGUUAGGCCGAA AGAAUUUA 869 1099 GUGACAGU U UAAACAGU 239 ACUGUUUA CUGAUGAGGCCGUUAGGCCGAA ACUGUCAC 870 1100 UGACAGUU U AAACAGUU 240 AACUGUUU CUGAUGAGGCCGUUAGGCCGAA AACUGUCA 871 1101 GACAGUUU A AACAGUUC 241 GAACUGUU CUGAUGAGGCCGUUAGGCCGAA AAACUGUC 872 1108 UAAACAGU U CUUCGUUG 242 CAACGAAG CUGAUGAGGCCGUUAGGCCGAA ACUGUUUA 873 1109 AAACAGUU C UUCGUUGC 243 GCAACGAA CUGAUGAGGCCGUUAGGCCGAA AACUGUUU 874 1111 ACAGUUCU U CGUUGCUU 244 AAGCAACG CUGAUGAGGCCGUUAGGCCGAA AGAACUGU 875 1112 CAGUUCUU C GUUGCUUA 245 UAAGCAAC CUGAUGAGGCCGUUAGGCCGAA AAGAACUG 876 1115 UUCUUCGU U GCUUAUGA 246 UCAUAAGC CUGAUGAGGCCGUUAGGCCGAA ACGAAGAA 877 1119 UCGUUGCU U AUGAAUGG 247 CCAUUCAU CUGAUGAGGCCGUUAGGCCGAA AGCAACGA 878

1120 CGUUGCUU A UGAAUGGU 248 ACCAUUCA CUGAUGAGGCCGUUAGGCCGAA AAGCAACG 879 1129 UGAAUGGU C UCAGAAAU 249 AUUUCUGA CUGAUGAGGCCGUUAGGCCGAA ACCAUUCA 880 1131 AAUGGUCU C AGAAAUAA 250 UUAUUUCU CUGAUGAGGCCGUUAGGCCGAA AGACCAUU 881 1138 UCAGAAAU A AUCAAAGG 251 CCUUUGAU CUGAUGAGGCCGUUAGGCCGAA AUUUCUGA 882 1141 GAAAUAAU C AAAGGAAG 252 CUUCCUUU CUGAUGAGGCCGUUAGGCCGAA AUUAUUUC 883 1160 AAAAAGAU C UUUGGCAC 253 GUGCCAAA CUGAUGAGGCCGUUAGGCCGAA AUCUUUUU 884 1162 AAAGAUCU U UGGCACCC 254 GGGUGCCA CUGAUGAGGCCGUUAGGCCGAA AGAUCUUU 885 1163 AAGAUCUU U GGCACCCA 255 UGGGUGCC CUGAUGAGGCCGUUAGGCCGAA AAGAUCUU 886 1175 ACCCAGAU U UGACCUUC 256 GAAGGUCA CUGAUGAGGCCGUUAGGCCGAA AUCUGGGU 887 1176 CCCAGAUU U GACCUUCC 257 GGAAGGUC CUGAUGAGGCCGUUAGGCCGAA AAUCUGGG 888 1182 UUUGACCU U CCUGACAU 258 AUGUCAGG CUGAUGAGGCCGUUAGGCCGAA AGGUCAAA 889 1183 UUGACCUU C CUGACAUG 259 CAUGUCAG CUGAUGAGGCCGUUAGGCCGAA AAGGUCAA 890 1205 AACAAAGU A UACUGUGG 260 CCACAGUA CUGAUGAGGCCGUUAGGCCGAA ACUUUGUU 891 1207 CAAAGUAU A CUGUGGAC 261 GUCCACAG CUGAUGAGGCCGUUAGGCCGAA AUACUUUG 892 1223 CAAGAGGU U UGGCAUGG 262 CCAUGCCA CUGAUGAGGCCGUUAGGCCGAA ACCUCUUG 893 1224 AAGAGGUU U GGCAUGGA 263 UCCAUGCC CUGAUGAGGCCGUUAGGCCGAA AACCUCUU 894 1234 GCAUGGAU U UUAAAGAA 264 UUCUUUAA CUGAUGAGGCCGUUAGGCCGAA AUCCAUGC 895 1235 CAUGGAUU U UAAAGAAA 265 UUUCUUUA CUGAUGAGGCCGUUAGGCCGAA AAUCCAUG 896 1236 AUGGAUUU U AAAGAAAU 266 AUUUCUUU CUGAUGAGGCCGUUAGGCCGAA AAAUCCAU 897 1237 UGGAUUUU A AAGAAAUA 267 UAUUUCUU CUGAUGAGGCCGUUAGGCCGAA AAAAUCCA 898 1245 AAAGAAAU A GAAUUAAU 268 AUUAAUUC CUGAUGAGGCCGUUAGGCCGAA AUUUCUUU 899 1250 AAUAGAAU U AAUUGGCU 269 AGCCAAUU CUGAUGAGGCCGUUAGGCCGAA AUUCUAUU 900 1251 AUAGAAUU A AUUGGCUC 270 GAGCCAAU CUGAUGAGGCCGUUAGGCCGAA AAUUCUAU 901 1254 GAAUUAAU U GGCUCAGG 271 CCUGAGCC CUGAUGAGGCCGUUAGGCCGAA AUUAAUUC 902 1259 AAUUGGCU C AGGUGGAU 272 AUCCACCU CUGAUGAGGCCGUUAGGCCGAA AGCCAAUU 903 1268 AGGUGGAU U UGGCCAAG 273 CUUGGCCA CUGAUGAGGCCGUUAGGCCGAA AUCCACCU 904 1269 GGUGGAUU U GGCCAAGU 274 ACUUGGCC CUGAUGAGGCCGUUAGGCCGAA AAUCCACC 905 1278 GGCCAAGU U UUCAAAGC 275 GCUUUGAA CUGAUGAGGCCGUUAGGCCGAA ACUUGGCC 906 1279 GCCAAGUU U UCAAAGCA 276 UGCUUUGA CUGAUGAGGCCGUUAGGCCGAA AACUUGGC 907 1280 CCAAGUUU U CAAAGCAA 277 UUGCUUUG CUGAUGAGGCCGUUAGGCCGAA AAACUUGG 908 1281 CAAGUUUU C AAAGCAAA 278 UUUGCUUU CUGAUGAGGCCGUUAGGCCGAA AAAACUUG 909 1299 CACAGAAU U GACGGAAA 279 UUUCCGUC CUGAUGAGGCCGUUAGGCCGAA AUUCUGUG 910 1312 GAAAGACU U ACGUUAUU 280 AAUAACGU CUGAUGAGGCCGUUAGGCCGAA AGUCUUUC 911 1313 AAAGACUU A CGUUAUUA 281 UAAUAACG CUGAUGAGGCCGUUAGGCCGAA AAGUCUUU 912 1317 ACUUACGU U AUUAAACG 282 CGUUUAAU CUGAUGAGGCCGUUAGGCCGAA ACGUAAGU 913 1318 CUUACGUU A UUAAACGU 283 ACGUUUAA CUGAUGAGGCCGUUAGGCCGAA AACGUAAG 914 1320 UACGUUAU U AAACGUGU 284 ACACGUUU CUGAUGAGGCCGUUAGGCCGAA AUAACGUA 915 1321 ACGUUAUU A AACGUGUU 285 AACACGUU CUGAUGAGGCCGUUAGGCCGAA AAUAACGU 916 1329 AAACGUGU U AAAUAUAA 286 UUAUAUUU CUGAUGAGGCCGUUAGGCCGAA ACACGUUU 917 1330 AACGUGUU A AAUAUAAU 287 AUUAUAUU CUGAUGAGGCCGUUAGGCCGAA AACACGUU 918 1334 UGUUAAAU A UAAUAACG 288 CGUUAUUA CUGAUGAGGCCGUUAGGCCGAA AUUUAACA 919 1336 UUAAAUAU A AUAACGAG 289 CUCGUUAU CUGAUGAGGCCGUUAGGCCGAA AUAUUUAA 920 1339 AAUAUAAU A ACGAGAAG 290 CUUCUCGU CUGAUGAGGCCGUUAGGCCGAA AUUAUAUU 921 1362 CGUGAAGU A AAAGCAUU 291 AAUGCUUU CUGAUGAGGCCGUUAGGCCGAA ACUUCACG 922 1370 AAAAGCAU U GGCAAAAC 292 GUUUUGCC CUGAUGAGGCCGUUAGGCCGAA AUGCUUUU 923 1380 GCAAAACU U GAUCAUGU 293 ACAUGAUC CUGAUGAGGCCGUUAGGCCGAA AGUUUUGC 924 1384 AACUUGAU C AUGUAAAU 294 AUUUACAU CUGAUGAGGCCGUUAGGCCGAA AUCAAGUU 925 1389 GAUCAUGU A AAUAUUGU 295 ACAAUAUU CUGAUGAGGCCGUUAGGCCGAA ACAUGAUC 926 1393 AUGUAAAU A UUGUUCAC 296 GUGAACAA CUGAUGAGGCCGUUAGGCCGAA AUUUACAU 927 1395 GUAAAUAU U GUUCACUA 297 UAGUGAAC CUGAUGAGGCCGUUAGGCCGAA AUAUUUAC 928 1398 AAUAUUGU U CACUACAA 298 UUGUAGUG CUGAUGAGGCCGUUAGGCCGAA ACAAUAUU 929 1399 AUAUUGUU C ACUACAAU 299 AUUGUAGU CUGAUGAGGCCGUUAGGCCGAA AACAAUAU 930 1403 UGUUCACU A CAAUGGCU 300 AGCCAUUG CUGAUGAGGCCGUUAGGCCGAA AGUGAACA 931 1414 AUGGCUGU U GGGAUGGA 301 UCCAUCCC CUGAUGAGGCCGUUAGGCCGAA ACAGCCAU 932 1424 GGAUGGAU U UGAUUAUG 302 CAUAAUCA CUGAUGAGGCCGUUAGGCCGAA AUCCAUCC 933 1425 GAUGGAUU U GAUUAUGA 303 UCAUAAUC CUGAUGAGGCCGUUAGGCCGAA AAUCCAUC 934 1429 GAUUUGAU U AUGAUCCU 304 AGGAUCAU CUGAUGAGGCCGUUAGGCCGAA AUCAAAUC 935 1430 AUUUGAUU A UGAUCCUG 305 CAGGAUCA CUGAUGAGGCCGUUAGGCCGAA AAUCAAAU 936 1435 AUUAUGAU C CUGAGACC 306 GGUCUCAG CUGAUGAGGCCGUUAGGCCGAA AUCAUAAU 937 1453 GUGAUGAU U CUCUUGAG 307 CUCAAGAG CUGAUGAGGCCGUUAGGCCGAA AUCAUCAC 938 1454 UGAUGAUU C UCUUGAGA 308 UCUCAAGA CUGAUGAGGCCGUUAGGCCGAA AAUCAUCA 939 1456 AUGAUUCU C UUGAGAGC 309 GCUCUCAA CUGAUGAGGCCGUUAGGCCGAA AGAAUCAU 940 1458 GAUUCUCU U GAGAGCAG 310 CUGCUCUC CUGAUGAGGCCGUUAGGCCGAA AGAGAAUC 941 1471 GCAGUGAU U AUGAUCCU 311 AGGAUCAU CUGAUGAGGCCGUUAGGCCGAA AUCACUGC 942 1472 CAGUGAUU A UGAUCCUG 312 CAGGAUCA CUGAUGAGGCCGUUAGGCCGAA AAUCACUG 943 1477 AUUAUGAU C CUGAGAAC 313 GUUCUCAG CUGAUGAGGCCGUUAGGCCGAA AUCAUAAU 944 1495 GCAAAAAU A GUUCAAGG 314 CCUUGAAC CUGAUGAGGCCGUUAGGCCGAA AUUUUUGC 945 1498 AAAAUAGU U CAAGGUCA 315 UGACCUUG CUGAUGAGGCCGUUAGGCCGAA ACUAUUUU 946 1499 AAAUAGUU C AAGGUCAA 316 UUGACCUU CUGAUGAGGCCGUUAGGCCGAA AACUAUUU 947 1505 UUCAAGGU C AAAGACUA 317 UAGUCUUU CUGAUGAGGCCGUUAGGCCGAA ACCUUGAA 948 1513 CAAAGACU A AGUGCCUU 318 AAGGCACU CUGAUGAGGCCGUUAGGCCGAA AGUCUUUG 949 1521 AAGUGCCU U UUCAUCCA 319 UGGAUGAA CUGAUGAGGCCGUUAGGCCGAA AGGCACUU 950 1522 AGUGCCUU U UCAUCCAA 320 UUGGAUGA CUGAUGAGGCCGUUAGGCCGAA AAGGCACU 951 1523 GUGCCUUU U CAUCCAAA 321 UUUGGAUG CUGAUGAGGCCGUUAGGCCGAA AAAGGCAC 952 1524 UGCCUUUU C AUCCAAAU 322 AUUUGGAU CUGAUGAGGCCGUUAGGCCGAA AAAAGGCA 953 1527 CUUUUCAU C CAAAUGGA 323 UCCAUUUG CUGAUGAGGCCGUUAGGCCGAA AUGAAAAG 954 1538 AAUGGAAU U CUGUGAUA 324 UAUCACAG CUGAUGAGGCCGUUAGGCCGAA AUUCCAUU 955 1539 AUGGAAUU C UGUGAUAA 325 UUAUCACA CUGAUGAGGCCGUUAGGCCGAA AAUUCCAU 956 1546 UCUGUGAU A AAGGGACC 326 GGUCCCUU CUGAUGAGGCCGUUAGGCCGAA AUCACAGA 957 1556 AGGGACCU U GGAACAAU 327 AUUGUUCC CUGAUGAGGCCGUUAGGCCGAA AGGUCCCU 958 1569 CAAUGGAU U GAAAAAAG 328 CUUUUUUC CUGAUGAGGCCGUUAGGCCGAA AUCCAUUG 959 1593 GAGAAACU A GACAAAGU 329 ACUUUGUC CUGAUGAGGCCGUUAGGCCGAA AGUUUCUC 960 1602 GACAAAGU U UUGGCUUU 330 AAAGCCAA CUGAUGAGGCCGUUAGGCCGAA ACUUUGUC 961 1603 ACAAAGUU U UGGCUUUG 331 CAAAGCCA CUGAUGAGGCCGUUAGGCCGAA AACUUUGU 962 1604 CAAAGUUU U GGCUUUGG 332 CCAAAGCC CUGAUGAGGCCGUUAGGCCGAA AAACUUUG 963 1609 UUUUGGCU U UGGAACUC 333 GAGUUCCA CUGAUGAGGCCGUUAGGCCGAA AGCCAAAA 964 1610 UUUGGCUU U GGAACUCU 334 AGAGUUCC CUGAUGAGGCCGUUAGGCCGAA AAGCCAAA 965 1617 UUGGAACU C UUUGAACA 335 UGUUCAAA CUGAUGAGGCCGUUAGGCCGAA AGUUCCAA 966 1619 GGAACUCU U UGAACAAA 336 UUUGUUCA CUGAUGAGGCCGUUAGGCCGAA AGAGUUCC 967 1620 GAACUCUU U GAACAAAU 337 AUUUGUUC CUGAUGAGGCCGUUAGGCCGAA AAGAGUUC 968 1629 GAACAAAU A ACAAAAGG 338 CCUUUUGU CUGAUGAGGCCGUUAGGCCGAA AUUUGUUC 969 1645 GGGUGGAU U AUAUACAU 339 AUGUAUAU CUGAUGAGGCCGUUAGGCCGAA AUCCACCC 970 1646 GGUGGAUU A UAUACAUU 340 AAUGUAUA CUGAUGAGGCCGUUAGGCCGAA AAUCCACC 971 1648 UGGAUUAU A UACAUUCA 341 UGAAUGUA CUGAUGAGGCCGUUAGGCCGAA AUAAUCCA 972 1650 GAUUAUAU A CAUUCAAA 342 UUUGAAUG CUGAUGAGGCCGUUAGGCCGAA AUAUAAUC 973 1654 AUAUACAU U CAAAAAAA 343 UUUUUUUG CUGAUGAGGCCGUUAGGCCGAA AUGUAUAU 974 1655 UAUACAUU C AAAAAAAU 344 AUUUUUUU CUGAUGAGGCCGUUAGGCCGAA AAUGUAUA 975 1664 AAAAAAAU U AAUUCAUA 345 UAUGAAUU CUGAUGAGGCCGUUAGGCCGAA AUUUUUUU 976 1665 AAAAAAUU A AUUCAUAG 346 CUAUGAAU CUGAUGAGGCCGUUAGGCCGAA AAUUUUUU 977 1668 AAAUUAAU U CAUAGAGA 347 UCUCUAUG CUGAUGAGGCCGUUAGGCCGAA AUUAAUUU 978 1669 AAUUAAUU C AUAGAGAU 348 AUCUCUAU CUGAUGAGGCCGUUAGGCCGAA AAUUAAUU 979 1672 UAAUUCAU A GAGAUCUU 349 AAGAUCUC CUGAUGAGGCCGUUAGGCCGAA AUGAAUUA 980 1678 AUAGAGAU C UUAAGCCA 350 UGGCUUAA CUGAUGAGGCCGUUAGGCCGAA AUCUCUAU 981 1680 AGAGAUCU U AAGCCAAG 351 CUUGGCUU CUGAUGAGGCCGUUAGGCCGAA AGAUCUCU 982 1681 GAGAUCUU A AGCCAAGU 352 ACUUGGCU CUGAUGAGGCCGUUAGGCCGAA AAGAUCUC 983 1690 AGCCAAGU A AUAUAUUC 353 GAAUAUAU CUGAUGAGGCCGUUAGGCCGAA ACUUGGCU 984 1693 CAAGUAAU A UAUUCUUA 354 UAAGAAUA CUGAUGAGGCCGUUAGGCCGAA AUUACUUG 985 1695 AGUAAUAU A UUCUUAGU 355 ACUAAGAA CUGAUGAGGCCGUUAGGCCGAA AUAUUACU 986 1697 UAAUAUAU U CUUAGUAG 356 CUACUAAG CUGAUGAGGCCGUUAGGCCGAA AUAUAUUA 987 1698 AAUAUAUU C UUAGUAGA 357 UCUACUAA CUGAUGAGGCCGUUAGGCCGAA AAUAUAUU 988 1700 UAUAUUCU U AGUAGAUA 358 UAUCUACU CUGAUGAGGCCGUUAGGCCGAA AGAAUAUA 989 1701 AUAUUCUU A GUAGAUAC 359 GUAUCUAC CUGAUGAGGCCGUUAGGCCGAA AAGAAUAU 990 1704 UUCUUAGU A GAUACAAA 360 UUUGUAUC CUGAUGAGGCCGUUAGGCCGAA ACUAAGAA 991 1708 UAGUAGAU A CAAAACAA 361 UUGUUUUG CUGAUGAGGCCGUUAGGCCGAA AUCUACUA 992 1719 AAACAAGU A AAGAUUGG 362 CCAAUCUU CUGAUGAGGCCGUUAGGCCGAA ACUUGUUU 993 1725 GUAAAGAU U GGAGACUU 363 AAGUCUCC CUGAUGAGGCCGUUAGGCCGAA AUCUUUAC 994 1733 UGGAGACU U UGGACUUG 364 CAAGUCCA CUGAUGAGGCCGUUAGGCCGAA AGUCUCCA 995 1734 GGAGACUU U GGACUUGU 365 ACAAGUCC CUGAUGAGGCCGUUAGGCCGAA AAGUCUCC 996 1740 UUUGGACU U GUAACAUC 366 GAUGUUAC CUGAUGAGGCCGUUAGGCCGAA AGUCCAAA 997 1743 GGACUUGU A ACAUCUCU 367 AGAGAUGU CUGAUGAGGCCGUUAGGCCGAA ACAAGUCC 998 1748 UGUAACAU C UCUGAAAA 368 UUUUCAGA CUGAUGAGGCCGUUAGGCCGAA AUGUUACA 999 1750 UAACAUCU C UGAAAAAU 369 AUUUUUCA CUGAUGAGGCCGUUAGGCCGAA AGAUGUUA 1000 1780 CAAGGAGU A AGGGAACU 370 AGUUCCCU CUGAUGAGGCCGUUAGGCCGAA ACUCCUUG 1001 1789 AGGGAACU U UGCGAUAC 371 GUAUCGCA CUGAUGAGGCCGUUAGGCCGAA AGUUCCCU 1002

1790 GGGAACUU U GCGAUACA 372 UGUAUCGC CUGAUGAGGCCGUUAGGCCGAA AAGUUCCC 1003 1796 UUUGCGAU A CAUGAGCC 373 GGCUCAUG CUGAUGAGGCCGUUAGGCCGAA AUCGCAAA 1004 1815 GAACAGAU U UCUUCGCA 374 UGCGAAGA CUGAUGAGGCCGUUAGGCCGAA AUCUGUUC 1005 1816 AACAGAUU U CUUCGCAA 375 UUGCGAAG CUGAUGAGGCCGUUAGGCCGAA AAUCUGUU 1006 1817 ACAGAUUU C UUCGCAAG 376 CUUGCGAA CUGAUGAGGCCGUUAGGCCGAA AAAUCUGU 1007 1819 AGAUUUCU U CGCAAGAC 377 GUCUUGCG CUGAUGAGGCCGUUAGGCCGAA AGAAAUCU 1008 1820 GAUUUCUU C GCAAGACU 378 AGUCUUGC CUGAUGAGGCCGUUAGGCCGAA AAGAAAUC 1009 1829 GCAAGACU A UGGAAAGG 379 CCUUUCCA CUGAUGAGGCCGUUAGGCCGAA AGUCUUGC 1010 1848 GUGGACCU C UACGCUUU 380 AAAGCGUA CUGAUGAGGCCGUUAGGCCGAA AGGUCCAC 1011 1850 GGACCUCU A CGCUUUGG 381 CCAAAGCG CUGAUGAGGCCGUUAGGCCGAA AGAGGUCC 1012 1855 UCUACGCU U UGGGGCUA 382 UAGCCCCA CUGAUGAGGCCGUUAGGCCGAA AGCGUAGA 1013 1856 CUACGCUU U GGGGCUAA 383 UUAGCCCC CUGAUGAGGCCGUUAGGCCGAA AAGCGUAG 1014 1863 UUGGGGCU A AUUCUUGC 384 GCAAGAAU CUGAUGAGGCCGUUAGGCCGAA AGCCCCAA 1015 1866 GGGCUAAU U CUUGCUGA 385 UCAGCAAG CUGAUGAGGCCGUUAGGCCGAA AUUAGCCC 1016 1867 GGCUAAUU C UUGCUGAA 386 UUCAGCAA CUGAUGAGGCCGUUAGGCCGAA AAUUAGCC 1017 1869 CUAAUUCU U GCUGAACU 387 AGUUCAGC CUGAUGAGGCCGUUAGGCCGAA AGAAUUAG 1018 1878 GCUGAACU U CUUCAUGU 388 ACAUGAAG CUGAUGAGGCCGUUAGGCCGAA AGUUCAGC 1019 1879 CUGAACUU C UUCAUGUA 389 UACAUGAA CUGAUGAGGCCGUUAGGCCGAA AAGUUCAG 1020 1881 GAACUUCU U CAUGUAUG 390 CAUACAUG CUGAUGAGGCCGUUAGGCCGAA AGAAGUUC 1021 1882 AACUUCUU C AUGUAUGU 391 ACAUACAU CUGAUGAGGCCGUUAGGCCGAA AAGAAGUU 1022 1887 CUUCAUGU A UGUGACAC 392 GUGUCACA CUGAUGAGGCCGUUAGGCCGAA ACAUGAAG 1023 1900 ACACUGCU U UUGAAACA 393 UGUUUCAA CUGAUGAGGCCGUUAGGCCGAA AGCAGUGU 1024 1901 CACUGCUU U UGAAACAU 394 AUGUUUCA CUGAUGAGGCCGUUAGGCCGAA AAGCAGUG 1025 1902 ACUGCUUU U GAAACAUC 395 GAUGUUUC CUGAUGAGGCCGUUAGGCCGAA AAAGCAGU 1026 1910 UGAAACAU C AAAGUUUU 396 AAAACUUU CUGAUGAGGCCGUUAGGCCGAA AUGUUUCA 1027 1916 AUCAAAGU U UUUCACAG 397 CUGUGAAA CUGAUGAGGCCGUUAGGCCGAA ACUUUGAU 1028 1917 UCAAAGUU U UUCACAGA 398 UCUGUGAA CUGAUGAGGCCGUUAGGCCGAA AACUUUGA 1029 1918 CAAAGUUU U UCACAGAC 399 GUCUGUGA CUGAUGAGGCCGUUAGGCCGAA AAACUUUG 1030 1919 AAAGUUUU U CACAGACC 400 GGUCUGUG CUGAUGAGGCCGUUAGGCCGAA AAAACUUU 1031 1920 AAGUUUUU C ACAGACCU 401 AGGUCUGU CUGAUGAGGCCGUUAGGCCGAA AAAAACUU 1032 1929 ACAGACCU A CGGGAUGG 402 CCAUCCCG CUGAUGAGGCCGUUAGGCCGAA AGGUCUGU 1033 1941 GAUGGCAU C AUCUCAGA 403 UCUGAGAU CUGAUGAGGCCGUUAGGCCGAA AUGCCAUC 1034 1944 GGCAUCAU C UCAGAUAU 404 AUAUCUGA CUGAUGAGGCCGUUAGGCCGAA AUGAUGCC 1035 1946 CAUCAUCU C AGAUAUAU 405 AUAUAUCU CUGAUGAGGCCGUUAGGCCGAA AGAUGAUG 1036 1951 UCUCAGAU A UAUUUGAU 406 AUCAAAUA CUGAUGAGGCCGUUAGGCCGAA AUCUGAGA 1037 1953 UCAGAUAU A UUUGAUAA 407 UUAUCAAA CUGAUGAGGCCGUUAGGCCGAA AUAUCUGA 1038 1955 AGAUAUAU U UGAUAAAA 408 UUUUAUCA CUGAUGAGGCCGUUAGGCCGAA AUAUAUCU 1039 1956 GAUAUAUU U GAUAAAAA 409 UUUUUAUC CUGAUGAGGCCGUUAGGCCGAA AAUAUAUC 1040 1960 UAUUUGAU A AAAAAGAA 410 UUCUUUUU CUGAUGAGGCCGUUAGGCCGAA AUCAAAUA 1041 1975 AAAAAACU C UUCUACAG 411 CUGUAGAA CUGAUGAGGCCGUUAGGCCGAA AGUUUUUU 1042 1977 AAAACUCU U CUACAGAA 412 UUCUGUAG CUGAUGAGGCCGUUAGGCCGAA AGAGUUUU 1043 1978 AAACUCUU C UACAGAAA 413 UUUCUGUA CUGAUGAGGCCGUUAGGCCGAA AAGAGUUU 1044 1980 ACUCUUCU A CAGAAAUU 414 AAUUUCUG CUGAUGAGGCCGUUAGGCCGAA AGAAGAGU 1045 1988 ACAGAAAU U ACUCUCAA 415 UUGAGAGU CUGAUGAGGCCGUUAGGCCGAA AUUUCUGU 1046 1989 CAGAAAUU A CUCUCAAA 416 UUUGAGAG CUGAUGAGGCCGUUAGGCCGAA AAUUUCUG 1047 1992 AAAUUACU C UCAAAGAA 417 UUCUUUGA CUGAUGAGGCCGUUAGGCCGAA AGUAAUUU 1048 1994 AUUACUCU C AAAGAAAC 418 GUUUCUUU CUGAUGAGGCCGUUAGGCCGAA AGAGUAAU 1049 2011 CUGAGGAU C GACCUAAC 419 GUUAGGUC CUGAUGAGGCCGUUAGGCCGAA AUCCUCAG 1050 2017 AUCGACCU A ACACAUCU 420 AGAUGUGU CUGAUGAGGCCGUUAGGCCGAA AGGUCGAU 1051 2024 UAACACAU C UGAAAUAC 421 GUAUUUCA CUGAUGAGGCCGUUAGGCCGAA AUGUGUUA 1052 2031 UCUGAAAU A CUAAGGAC 422 GUCCUUAG CUGAUGAGGCCGUUAGGCCGAA AUUUCAGA 1053 2034 GAAAUACU A AGGACCUU 423 AAGGUCCU CUGAUGAGGCCGUUAGGCCGAA AGUAUUUC 1054 2042 AAGGACCU U GACUGUGU 424 ACACAGUC CUGAUGAGGCCGUUAGGCCGAA AGGUCCUU 1055 2089 ACACAUGU U AGAGCCCU 425 AGGGCUCU CUGAUGAGGCCGUUAGGCCGAA ACAUGUGU 1056 2090 CACAUGUU A GAGCCCUU 426 AAGGGCUC CUGAUGAGGCCGUUAGGCCGAA AACAUGUG 1057 2098 AGAGCCCU U CUGAAAAA 427 UUUUUCAG CUGAUGAGGCCGUUAGGCCGAA AGGGCUCU 1058 2099 GAGCCCUU C UGAAAAAG 428 CUUUUUCA CUGAUGAGGCCGUUAGGCCGAA AAGGGCUC 1059 2109 GAAAAAGU A UCCUGCUU 429 AAGCAGGA CUGAUGAGGCCGUUAGGCCGAA ACUUUUUC 1060 2111 AAAAGUAU C CUGCUUCU 430 AGAAGCAG CUGAUGAGGCCGUUAGGCCGAA AUACUUUU 1061 2117 AUCCUGCU U CUGAUAUG 431 CAUAUCAG CUGAUGAGGCCGUUAGGCCGAA AGCAGGAU 1062 2118 UCCUGCUU C UGAUAUGC 432 GCAUAUCA CUGAUGAGGCCGUUAGGCCGAA AAGCAGGA 1063 2123 CUUCUGAU A UGCAGUUU 433 AAACUGCA CUGAUGAGGCCGUUAGGCCGAA AUCAGAAG 1064 2130 UAUGCAGU U UUCCUUAA 434 UUAAGGAA CUGAUGAGGCCGUUAGGCCGAA ACUGCAUA 1065 2131 AUGCAGUU U UCCUUAAA 435 UUUAAGGA CUGAUGAGGCCGUUAGGCCGAA AACUGCAU 1066 2132 UGCAGUUU U CCUUAAAU 436 AUUUAAGG CUGAUGAGGCCGUUAGGCCGAA AAACUGCA 1067 2133 GCAGUUUU C CUUAAAUU 437 AAUUUAAG CUGAUGAGGCCGUUAGGCCGAA AAAACUGC 1068 2136 GUUUUCCU U AAAUUAUC 438 GAUAAUUU CUGAUGAGGCCGUUAGGCCGAA AGGAAAAC 1069 2137 UUUUCCUU A AAUUAUCU 439 AGAUAAUU CUGAUGAGGCCGUUAGGCCGAA AAGGAAAA 1070 2141 CCUUAAAU U AUCUAAAA 440 UUUUAGAU CUGAUGAGGCCGUUAGGCCGAA AUUUAAGG 1071 2142 CUUAAAUU A UCUAAAAU 441 AUUUUAGA CUGAUGAGGCCGUUAGGCCGAA AAUUUAAG 1072 2144 UAAAUUAU C UAAAAUCU 442 AGAUUUUA CUGAUGAGGCCGUUAGGCCGAA AUAAUUUA 1073 2146 AAUUAUCU A AAAUCUGC 443 GCAGAUUU CUGAUGAGGCCGUUAGGCCGAA AGAUAAUU 1074 2151 UCUAAAAU C UGCUAGGG 444 CCCUAGCA CUGAUGAGGCCGUUAGGCCGAA AUUUUAGA 1075 2156 AAUCUGCU A GGGAAUAU 445 AUAUUCCC CUGAUGAGGCCGUUAGGCCGAA AGCAGAUU 1076 2163 UAGGGAAU A UCAAUAGA 446 UCUAUUGA CUGAUGAGGCCGUUAGGCCGAA AUUCCCUA 1077 2165 GGGAAUAU C AAUAGAUA 447 UAUCUAUU CUGAUGAGGCCGUUAGGCCGAA AUAUUCCC 1078 2169 AUAUCAAU A GAUAUUUA 448 UAAAUAUC CUGAUGAGGCCGUUAGGCCGAA AUUGAUAU 1079 2173 CAAUAGAU A UUUACCUU 449 AAGGUAAA CUGAUGAGGCCGUUAGGCCGAA AUCUAUUG 1080 2175 AUAGAUAU U UACCUUUU 450 AAAAGGUA CUGAUGAGGCCGUUAGGCCGAA AUAUCUAU 1081 2176 UAGAUAUU U ACCUUUUA 451 UAAAAGGU CUGAUGAGGCCGUUAGGCCGAA AAUAUCUA 1082 2177 AGAUAUUU A CCUUUUAU 452 AUAAAAGG CUGAUGAGGCCGUUAGGCCGAA AAAUAUCU 1083 2181 AUUUACCU U UUAUUUUA 453 UAAAAUAA CUGAUGAGGCCGUUAGGCCGAA AGGUAAAU 1084 2182 UUUACCUU U UAUUUUAA 454 UUAAAAUA CUGAUGAGGCCGUUAGGCCGAA AAGGUAAA 1085 2183 UUACCUUU U AUUUUAAU 455 AUUAAAAU CUGAUGAGGCCGUUAGGCCGAA AAAGGUAA 1086

2184 UACCUUUU A UUUUAAUG 456 CAUUAAAA CUGAUGAGGCCGUUAGGCCGAA AAAAGGUA 1087 2186 CCUUUUAU U UUAAUGUU 457 AACAUUAA CUGAUGAGGCCGUUAGGCCGAA AUAAAAGG 1088 2187 CUUUUAUU U UAAUGUUU 458 AAACAUUA CUGAUGAGGCCGUUAGGCCGAA AAUAAAAG 1089 2188 UUUUAUUU U AAUGUUUC 459 GAAACAUU CUGAUGAGGCCGUUAGGCCGAA AAAUAAAA 1090 2189 UUUAUUUU A AUGUUUCC 460 GGAAACAU CUGAUGAGGCCGUUAGGCCGAA AAAAUAAA 1091 2194 UUUAAUGU U UCCUUUAA 461 UUAAAGGA CUGAUGAGGCCGUUAGGCCGAA ACAUUAAA 1092 2195 UUAAUGUU U CCUUUAAU 462 AUUAAAGG CUGAUGAGGCCGUUAGGCCGAA AACAUUAA 1093 2196 UAAUGUUU C CUUUAAUU 463 AAUUAAAG CUGAUGAGGCCGUUAGGCCGAA AAACAUUA 1094 2199 UGUUUCCU U UAAUUUUU 464 AAAAAUUA CUGAUGAGGCCGUUAGGCCGAA AGGAAACA 1095 2200 GUUUCCUU U AAUUUUUU 465 AAAAAAUU CUGAUGAGGCCGUUAGGCCGAA AAGGAAAC 1096 2201 UUUCCUUU A AUUUUUUA 466 UAAAAAAU CUGAUGAGGCCGUUAGGCCGAA AAAGGAAA 1097 2204 CCUUUAAU U UUUUACUA 467 UAGUAAAA CUGAUGAGGCCGUUAGGCCGAA AUUAAAGG 1098 2205 CUUUAAUU U UUUACUAU 468 AUAGUAAA CUGAUGAGGCCGUUAGGCCGAA AAUUAAAG 1099 2206 UUUAAUUU U UUACUAUU 469 AAUAGUAA CUGAUGAGGCCGUUAGGCCGAA AAAUUAAA 1100 2207 UUAAUUUU U UACUAUUU 470 AAAUAGUA CUGAUGAGGCCGUUAGGCCGAA AAAAUUAA 1101 2208 UAAUUUUU U ACUAUUUU 471 AAAAUAGU CUGAUGAGGCCGUUAGGCCGAA AAAAAUUA 1102 2209 AAUUUUUU A CUAUUUUU 472 AAAAAUAG CUGAUGAGGCCGUUAGGCCGAA AAAAAAUU 1103 2212 UUUUUACU A UUUUUACU 473 AGUAAAAA CUGAUGAGGCCGUUAGGCCGAA AGUAAAAA 1104 2214 UUUACUAU U UUUACUAA 474 UUAGUAAA CUGAUGAGGCCGUUAGGCCGAA AUAGUAAA 1105 2215 UUACUAUU U UUACUAAU 475 AUUAGUAA CUGAUGAGGCCGUUAGGCCGAA AAUAGUAA 1106 2216 UACUAUUU U UACUAAUC 476 GAUUAGUA CUGAUGAGGCCGUUAGGCCGAA AAAUAGUA 1107 2217 ACUAUUUU U ACUAAUCU 477 AGAUUAGU CUGAUGAGGCCGUUAGGCCGAA AAAAUAGU 1108 2218 CUAUUUUU A CUAAUCUU 478 AAGAUUAG CUGAUGAGGCCGUUAGGCCGAA AAAAAUAG 1109 2221 UUUUUACU A AUCUUUCU 479 AGAAAGAU CUGAUGAGGCCGUUAGGCCGAA AGUAAAAA 1110 2224 UUACUAAU C UUUCUGCA 480 UGCAGAAA CUGAUGAGGCCGUUAGGCCGAA AUUAGUAA 1111 2226 ACUAAUCU U UCUGCAGA 481 UCUGCAGA CUGAUGAGGCCGUUAGGCCGAA AGAUUAGU 1112 2227 CUAAUCUU U CUGCAGAA 482 UUCUGCAG CUGAUGAGGCCGUUAGGCCGAA AAGAUUAG 1113 2228 UAAUCUUU C UGCAGAAA 483 UUUCUGCA CUGAUGAGGCCGUUAGGCCGAA AAAGAUUA 1114 2246 AGAAAGGU U UUCUUCUU 484 AAGAAGAA CUGAUGAGGCCGUUAGGCCGAA ACCUUUCU 1115 2247 GAAAGGUU U UCUUCUUU 485 AAAGAAGA CUGAUGAGGCCGUUAGGCCGAA AACCUUUC 1116 2248 AAAGGUUU U CUUCUUUU 486 AAAAGAAG CUGAUGAGGCCGUUAGGCCGAA AAACCUUU 1117 2249 AAGGUUUU C UUCUUUUU 487 AAAAAGAA CUGAUGAGGCCGUUAGGCCGAA AAAACCUU 1118 2251 GGUUUUCU U CUUUUUGC 488 GCAAAAAG CUGAUGAGGCCGUUAGGCCGAA AGAAAACC 1119 2252 GUUUUCUU C UUUUUGCU 489 AGCAAAAA CUGAUGAGGCCGUUAGGCCGAA AAGAAAAC 1120 2254 UUUCUUCU U UUUGCUUC 490 GAAGCAAA CUGAUGAGGCCGUUAGGCCGAA AGAAGAAA 1121 2255 UUCUUCUU U UUGCUUCA 491 UGAAGCAA CUGAUGAGGCCGUUAGGCCGAA AAGAAGAA 1122 2256 UCUUCUUU U UGCUUCAA 492 UUGAAGCA CUGAUGAGGCCGUUAGGCCGAA AAAGAAGA 1123 2257 CUUCUUUU U GCUUCAAA 493 UUUGAAGC CUGAUGAGGCCGUUAGGCCGAA AAAAGAAG 1124 2261 UUUUUGCU U CAAAAACA 494 UGUUUUUG CUGAUGAGGCCGUUAGGCCGAA AGCAAAAA 1125 2262 UUUUGCUU C AAAAACAU 495 AUGUUUUU CUGAUGAGGCCGUUAGGCCGAA AAGCAAAA 1126 2271 AAAAACAU U CUUACAUU 496 AAUGUAAG CUGAUGAGGCCGUUAGGCCGAA AUGUUUUU 1127 2272 AAAACAUU C UUACAUUU 497 AAAUGUAA CUGAUGAGGCCGUUAGGCCGAA AAUGUUUU 1128 2274 AACAUUCU U ACAUUUUA 498 UAAAAUGU CUGAUGAGGCCGUUAGGCCGAA AGAAUGUU 1129 2275 ACAUUCUU A CAUUUUAC 499 GUAAAAUG CUGAUGAGGCCGUUAGGCCGAA AAGAAUGU 1130 2279 UCUUACAU U UUACUUUU 500 AAAAGUAA CUGAUGAGGCCGUUAGGCCGAA AUGUAAGA 1131 2280 CUUACAUU U UACUUUUU 501 AAAAAGUA CUGAUGAGGCCGUUAGGCCGAA AAUGUAAG 1132 2281 UUACAUUU U ACUUUUUC 502 GAAAAAGU CUGAUGAGGCCGUUAGGCCGAA AAAUGUAA 1133 2282 UACAUUUU A CUUUUUCC 503 GGAAAAAG CUGAUGAGGCCGUUAGGCCGAA AAAAUGUA 1134 2285 AUUUUACU U UUUCCUGG 504 CCAGGAAA CUGAUGAGGCCGUUAGGCCGAA AGUAAAAU 1135 2286 UUUUACUU U UUCCUGGC 505 GCCAGGAA CUGAUGAGGCCGUUAGGCCGAA AAGUAAAA 1136 2287 UUUACUUU U UCCUGGCU 506 AGCCAGGA CUGAUGAGGCCGUUAGGCCGAA AAAGUAAA 1137 2288 UUACUUUU U CCUGGCUC 507 GAGCCAGG CUGAUGAGGCCGUUAGGCCGAA AAAAGUAA 1138 2289 UACUUUUU C CUGGCUCA 508 UGAGCCAG CUGAUGAGGCCGUUAGGCCGAA AAAAAGUA 1139 2296 UCCUGGCU C AUCUCUUU 509 AAAGAGAU CUGAUGAGGCCGUUAGGCCGAA AGCCAGGA 1140 2299 UGGCUCAU C UCUUUAUU 510 AAUAAAGA CUGAUGAGGCCGUUAGGCCGAA AUGAGCCA 1141 2301 GCUCAUCU C UUUAUUCU 511 AGAAUAAA CUGAUGAGGCCGUUAGGCCGAA AGAUGAGC 1142 2303 UCAUCUCU U UAUUCUUU 512 AAAGAAUA CUGAUGAGGCCGUUAGGCCGAA AGAGAUGA 1143 2304 CAUCUCUU U AUUCUUUU 513 AAAAGAAU CUGAUGAGGCCGUUAGGCCGAA AAGAGAUG 1144 2305 AUCUCUUU A UUCUUUUU 514 AAAAAGAA CUGAUGAGGCCGUUAGGCCGAA AAAGAGAU 1145 2307 CUCUUUAU U CUUUUUUU 515 AAAAAAAG CUGAUGAGGCCGUUAGGCCGAA AUAAAGAG 1146 2308 UCUUUAUU C UUUUUUUU 516 AAAAAAAA CUGAUGAGGCCGUUAGGCCGAA AAUAAAGA 1147 2310 UUUAUUCU U UUUUUUUU 517 AAAAAAAA CUGAUGAGGCCGUUAGGCCGAA AGAAUAAA 1148 2311 UUAUUCUU U UUUUUUUU 518 AAAAAAAA CUGAUGAGGCCGUUAGGCCGAA AAGAAUAA 1149 2312 UAUUCUUU U UUUUUUUU 519 AAAAAAAA CUGAUGAGGCCGUUAGGCCGAA AAAGAAUA 1150 2313 AUUCUUUU U UUUUUUUU 520 AAAAAAAA CUGAUGAGGCCGUUAGGCCGAA AAAAGAAU 1151 2314 UUCUUUUU U UUUUUUUU 521 AAAAAAAA CUGAUGAGGCCGUUAGGCCGAA AAAAAGAA 1152 2315 UCUUUUUU U UUUUUUUA 522 UAAAAAAA CUGAUGAGGCCGUUAGGCCGAA AAAAAAGA 1153 2316 CUUUUUUU U UUUUUUAA 523 UUAAAAAA CUGAUGAGGCCGUUAGGCCGAA AAAAAAAG 1154 2317 UUUUUUUU U UUUUUAAA 524 UUUAAAAA CUGAUGAGGCCGUUAGGCCGAA AAAAAAAA 1155 2318 UUUUUUUU U UUUUAAAG 525 CUUUAAAA CUGAUGAGGCCGUUAGGCCGAA AAAAAAAA 1156 2319 UUUUUUUU U UUUAAAGA 526 UCUUUAAA CUGAUGAGGCCGUUAGGCCGAA AAAAAAAA 1157 2320 UUUUUUUU U UUAAAGAC 527 GUCUUUAA CUGAUGAGGCCGUUAGGCCGAA AAAAAAAA 1158 2321 UUUUUUUU U UAAAGACA 528 UGUCUUUA CUGAUGAGGCCGUUAGGCCGAA AAAAAAAA 1159 2322 UUUUUUUU U AAAGACAG 529 CUGUCUUU CUGAUGAGGCCGUUAGGCCGAA AAAAAAAA 1160 2323 UUUUUUUU A AAGACAGA 530 UCUGUCUU CUGAUGAGGCCGUUAGGCCGAA AAAAAAAA 1161 2334 GACAGAGU C UCGCUCUG 531 CAGAGCGA CUGAUGAGGCCGUUAGGCCGAA ACUCUGUC 1162 2336 CAGAGUCU C GCUCUGUU 532 AACAGAGC CUGAUGAGGCCGUUAGGCCGAA AGACUCUG 1163 2340 GUCUCGCU C UGUUGCCC 533 GGGCAACA CUGAUGAGGCCGUUAGGCCGAA AGCGAGAC 1164 2344 CGCUCUGU U GCCCAGGC 534 GCCUGGGC CUGAUGAGGCCGUUAGGCCGAA ACAGAGCG 1165 2372 GACACAGU C UUGGCUCA 535 UGAGCCAA CUGAUGAGGCCGUUAGGCCGAA ACUGUGUC 1166 2374 CACAGUCU U GGCUCACU 536 AGUGAGCC CUGAUGAGGCCGUUAGGCCGAA AGACUGUG 1167 2379 UCUUGGCU C ACUGCAAC 537 GUUGCAGU CUGAUGAGGCCGUUAGGCCGAA AGCCAAGA 1168 2389 CUGCAACU U CUGCCUCU 538 AGAGGCAG CUGAUGAGGCCGUUAGGCCGAA AGUUGCAG 1169 2390 UGCAACUU C UGCCUCUU 539 AAGAGGCA CUGAUGAGGCCGUUAGGCCGAA AAGUUGCA 1170

2396 UUCUGCCU C UUGGGUUC 540 GAACCCAA CUGAUGAGGCCGUUAGGCCGAA AGGCAGAA 1171 2398 CUGCCUCU U GGGUUCAA 541 UUGAACCC CUGAUGAGGCCGUUAGGCCGAA AGAGGCAG 1172 2403 UCUUGGGU U CAAGUGAU 542 AUCACUUG CUGAUGAGGCCGUUAGGCCGAA ACCCAAGA 1173 2404 CUUGGGUU C AAGUGAUU 543 AAUCACUU CUGAUGAGGCCGUUAGGCCGAA AACCCAAG 1174 2412 CAAGUGAU U CUCCUGCC 544 GGCAGGAG CUGAUGAGGCCGUUAGGCCGAA AUCACUUG 1175 2413 AAGUGAUU C UCCUGCCU 545 AGGCAGGA CUGAUGAGGCCGUUAGGCCGAA AAUCACUU 1176 2415 GUGAUUCU C CUGCCUCA 546 UGAGGCAG CUGAUGAGGCCGUUAGGCCGAA AGAAUCAC 1177 2422 UCCUGCCU C AGCCUCCU 547 AGGAGGCU CUGAUGAGGCCGUUAGGCCGAA AGGCAGGA 1178 2428 CUCAGCCU C CUGAGUAG 548 CUACUCAG CUGAUGAGGCCGUUAGGCCGAA AGGCUGAG 1179 2435 UCCUGAGU A GCUGGAUU 549 AAUCCAGC CUGAUGAGGCCGUUAGGCCGAA ACUCAGGA 1180 2443 AGCUGGAU U ACAGGCAU 550 AUGCCUGU CUGAUGAGGCCGUUAGGCCGAA AUCCAGCU 1181 2444 GCUGGAUU A CAGGCAUG 551 CAUGCCUG CUGAUGAGGCCGUUAGGCCGAA AAUCCAGC 1182 2469 ACCCAACU A AUUUUUGU 552 ACAAAAAU CUGAUGAGGCCGUUAGGCCGAA AGUUGGGU 1183 2472 CAACUAAU U UUUGUGUU 553 AACACAAA CUGAUGAGGCCGUUAGGCCGAA AUUAGUUG 1184 2473 AACUAAUU U UUGUGUUU 554 AAACACAA CUGAUGAGGCCGUUAGGCCGAA AAUUAGUU 1185 2474 ACUAAUUU U UGUGUUUU 555 AAAACACA CUGAUGAGGCCGUUAGGCCGAA AAAUUAGU 1186 2475 CUAAUUUU U GUGUUUUU 556 AAAAACAC CUGAUGAGGCCGUUAGGCCGAA AAAAUUAG 1187 2480 UUUUGUGU U UUUAAUAA 557 UUAUUAAA CUGAUGAGGCCGUUAGGCCGAA ACACAAAA 1188 2481 UUUGUGUU U UUAAUAAA 558 UUUAUUAA CUGAUGAGGCCGUUAGGCCGAA AACACAAA 1189 2482 UUGUGUUU U UAAUAAAG 559 CUUUAUUA CUGAUGAGGCCGUUAGGCCGAA AAACACAA 1190 2483 UGUGUUUU U AAUAAAGA 560 UCUUUAUU CUGAUGAGGCCGUUAGGCCGAA AAAACACA 1191 2484 GUGUUUUU A AUAAAGAC 561 GUCUUUAU CUGAUGAGGCCGUUAGGCCGAA AAAAACAC 1192 2487 UUUUUAAU A AAGACAGG 562 CCUGUCUU CUGAUGAGGCCGUUAGGCCGAA AUUAAAAA 1193 2498 GACAGGGU U UCACCAUG 563 CAUGGUGA CUGAUGAGGCCGUUAGGCCGAA ACCCUGUC 1194 2499 ACAGGGUU U CACCAUGU 564 ACAUGGUG CUGAUGAGGCCGUUAGGCCGAA AACCCUGU 1195 2500 CAGGGUUU C ACCAUGUU 565 AACAUGGU CUGAUGAGGCCGUUAGGCCGAA AAACCCUG 1196 2508 CACCAUGU U GGCCAGGC 566 GCCUGGCC CUGAUGAGGCCGUUAGGCCGAA ACAUGGUG 1197 2521 AGGCUGGU C UCAAACUC 567 GAGUUUGA CUGAUGAGGCCGUUAGGCCGAA ACCAGCCU 1198 2523 GCUGGUCU C AAACUCCU 568 AGGAGUUU CUGAUGAGGCCGUUAGGCCGAA AGACCAGC 1199 2529 CUCAAACU C CUGACCUC 569 GAGGUCAG CUGAUGAGGCCGUUAGGCCGAA AGUUUGAG 1200 2537 CCUGACCU C AAGUAAUC 570 GAUUACUU CUGAUGAGGCCGUUAGGCCGAA AGGUCAGG 1201 2542 CCUCAAGU A AUCCACCU 571 AGGUGGAU CUGAUGAGGCCGUUAGGCCGAA ACUUGAGG 1202 2545 CAAGUAAU C CACCUGCC 572 GGCAGGUG CUGAUGAGGCCGUUAGGCCGAA AUUACUUG 1203 2555 ACCUGCCU C GGCCUCCC 573 GGGAGGCC CUGAUGAGGCCGUUAGGCCGAA AGGCAGGU 1204 2561 CUCGGCCU C CCAAAGUG 574 CACUUUGG CUGAUGAGGCCGUUAGGCCGAA AGGCCGAG 1205 2577 GCUGGGAU U ACAGGGAU 575 AUCCCUGU CUGAUGAGGCCGUUAGGCCGAA AUCCCAGC 1206 2578 CUGGGAUU A CAGGGAUG 576 CAUCCCUG CUGAUGAGGCCGUUAGGCCGAA AAUCCCAG 1207 2605 CCCAGCCU C AUCUCUUU 577 AAAGAGAU CUGAUGAGGCCGUUAGGCCGAA AGGCUGGG 1208 2608 AGCCUCAU C UCUUUGUU 578 AACAAAGA CUGAUGAGGCCGUUAGGCCGAA AUGAGGCU 1209 2610 CCUCAUCU C UUUGUUCU 579 AGAACAAA CUGAUGAGGCCGUUAGGCCGAA AGAUGAGG 1210 2612 UCAUCUCU U UGUUCUAA 580 UUAGAACA CUGAUGAGGCCGUUAGGCCGAA AGAGAUGA 1211 2613 CAUCUCUU U GUUCUAAA 581 UUUAGAAC CUGAUGAGGCCGUUAGGCCGAA AAGAGAUG 1212 2616 CUCUUUGU U CUAAAGAU 582 AUCUUUAG CUGAUGAGGCCGUUAGGCCGAA ACAAAGAG 1213 2617 UCUUUGUU C UAAAGAUG 583 CAUCUUUA CUGAUGAGGCCGUUAGGCCGAA AACAAAGA 1214 2619 UUUGUUCU A AAGAUGGA 584 UCCAUCUU CUGAUGAGGCCGUUAGGCCGAA AGAACAAA 1215 2644 CCCCAAAU U UUCUUUUU 585 AAAAAGAA CUGAUGAGGCCGUUAGGCCGAA AUUUGGGG 1216 2645 CCCAAAUU U UCUUUUUA 586 UAAAAAGA CUGAUGAGGCCGUUAGGCCGAA AAUUUGGG 1217 2646 CCAAAUUU U CUUUUUAU 587 AUAAAAAG CUGAUGAGGCCGUUAGGCCGAA AAAUUUGG 1218 2647 CAAAUUUU C UUUUUAUA 588 UAUAAAAA CUGAUGAGGCCGUUAGGCCGAA AAAAUUUG 1219 2649 AAUUUUCU U UUUAUACU 589 AGUAUAAA CUGAUGAGGCCGUUAGGCCGAA AGAAAAUU 1220 2650 AUUUUCUU U UUAUACUA 590 UAGUAUAA CUGAUGAGGCCGUUAGGCCGAA AAGAAAAU 1221 2651 UUUUCUUU U UAUACUAU 591 AUAGUAUA CUGAUGAGGCCGUUAGGCCGAA AAAGAAAA 1222 2652 UUUCUUUU U AUACUAUU 592 AAUAGUAU CUGAUGAGGCCGUUAGGCCGAA AAAAGAAA 1223 2653 UUCUUUUU A UACUAUUA 593 UAAUAGUA CUGAUGAGGCCGUUAGGCCGAA AAAAAGAA 1224 2655 CUUUUUAU A CUAUUAAU 594 AUUAAUAG CUGAUGAGGCCGUUAGGCCGAA AUAAAAAG 1225 2658 UUUAUACU A UUAAUGAA 595 UUCAUUAA CUGAUGAGGCCGUUAGGCCGAA AGUAUAAA 1226 2660 UAUACUAU U AAUGAAUC 596 GAUUCAUU CUGAUGAGGCCGUUAGGCCGAA AUAGUAUA 1227 2661 AUACUAUU A AUGAAUCA 597 UGAUUCAU CUGAUGAGGCCGUUAGGCCGAA AAUAGUAU 1228 2668 UAAUGAAU C AAUCAAUU 598 AAUUGAUU CUGAUGAGGCCGUUAGGCCGAA AUUCAUUA 1229 2672 GAAUCAAU C AAUUCAUA 599 UAUGAAUU CUGAUGAGGCCGUUAGGCCGAA AUUGAUUC 1230 2676 CAAUCAAU U CAUAUCUA 600 UAGAUAUG CUGAUGAGGCCGUUAGGCCGAA AUUGAUUG 1231 2677 AAUCAAUU C AUAUCUAU 601 AUAGAUAU CUGAUGAGGCCGUUAGGCCGAA AAUUGAUU 1232 2680 CAAUUCAU A UCUAUUUA 602 UAAAUAGA CUGAUGAGGCCGUUAGGCCGAA AUGAAUUG 1233 2682 AUUCAUAU C UAUUUAUU 603 AAUAAAUA CUGAUGAGGCCGUUAGGCCGAA AUAUGAAU 1234 2684 UCAUAUCU A UUUAUUAA 604 UUAAUAAA CUGAUGAGGCCGUUAGGCCGAA AGAUAUGA 1235 2686 AUAUCUAU U UAUUAAAU 605 AUUUAAUA CUGAUGAGGCCGUUAGGCCGAA AUAGAUAU 1236 2687 UAUCUAUU U AUUAAAUU 606 AAUUUAAU CUGAUGAGGCCGUUAGGCCGAA AAUAGAUA 1237 2688 AUCUAUUU A UUAAAUUU 607 AAAUUUAA CUGAUGAGGCCGUUAGGCCGAA AAAUAGAU 1238 2690 CUAUUUAU U AAAUUUCU 608 AGAAAUUU CUGAUGAGGCCGUUAGGCCGAA AUAAAUAG 1239 2691 UAUUUAUU A AAUUUCUA 609 UAGAAAUU CUGAUGAGGCCGUUAGGCCGAA AAUAAAUA 1240 2695 UAUUAAAU U UCUACCGC 610 GCGGUAGA CUGAUGAGGCCGUUAGGCCGAA AUUUAAUA 1241 2696 AUUAAAUU U CUACCGCU 611 AGCGGUAG CUGAUGAGGCCGUUAGGCCGAA AAUUUAAU 1242 2697 UUAAAUUU C UACCGCUU 612 AAGCGGUA CUGAUGAGGCCGUUAGGCCGAA AAAUUUAA 1243 2699 AAAUUUCU A CCGCUUUU 613 AAAAGCGG CUGAUGAGGCCGUUAGGCCGAA AGAAAUUU 1244 2705 CUACCGCU U UUAGGCCA 614 UGGCCUAA CUGAUGAGGCCGUUAGGCCGAA AGCGGUAG 1245 2706 UACCGCUU U UAGGCCAA 615 UUGGCCUA CUGAUGAGGCCGUUAGGCCGAA AAGCGGUA 1246 2707 ACCGCUUU U AGGCCAAA 616 UUUGGCCU CUGAUGAGGCCGUUAGGCCGAA AAAGCGGU 1247 2708 CCGCUUUU A GGCCAAAA 617 UUUUGGCC CUGAUGAGGCCGUUAGGCCGAA AAAAGCGG 1248 2723 AAAAAUGU A AGAUCGUU 618 AACGAUCU CUGAUGAGGCCGUUAGGCCGAA ACAUUUUU 1249 2728 UGUAAGAU C GUUCUCUG 619 CAGAGAAC CUGAUGAGGCCGUUAGGCCGAA AUCUUACA 1250 2731 AAGAUCGU U CUCUGCCU 620 AGGCAGAG CUGAUGAGGCCGUUAGGCCGAA ACGAUCUU 1251 2732 AGAUCGUU C UCUGCCUC 621 GAGGCAGA CUGAUGAGGCCGUUAGGCCGAA AACGAUCU 1252 2734 AUCGUUCU C UGCCUCAC 622 GUGAGGCA CUGAUGAGGCCGUUAGGCCGAA AGAACGAU 1253

2740 CUCUGCCU C ACAUAGCU 623 AGCUAUGU CUGAUGAGGCCGUUAGGCCGAA AGGCAGAG 1254 2745 CCUCACAU A GCUUACAA 624 UUGUAAGC CUGAUGAGGCCGUUAGGCCGAA AUGUGAGG 1255 2749 ACAUAGCU U ACAAGCCA 625 UGGCUUGU CUGAUGAGGCCGUUAGGCCGAA AGCUAUGU 1256 2750 CAUAGCUU A CAAGCCAG 626 CUGGCUUG CUGAUGAGGCCGUUAGGCCGAA AAGCUAUG 1257 2769 GGAGAAAU A UGGUACUC 627 GAGUACCA CUGAUGAGGCCGUUAGGCCGAA AUUUCUCC 1258 2774 AAUAUGGU A CUCAUUAA 628 UUAAUGAG CUGAUGAGGCCGUUAGGCCGAA ACCAUAUU 1259 2777 AUGGUACU C AUUAAAAA 629 UUUUUAAU CUGAUGAGGCCGUUAGGCCGAA AGUACCAU 1260 2780 GUACUCAU U AAAAAAAA 630 UUUUUUUU CUGAUGAGGCCGUUAGGCCGAA AUGAGUAC 1261 2781 UACUCAUU A AAAAAAAA 631 UUUUUUUU CUGAUGAGGCCGUUAGGCCGAA AAUGAGUA 1262 Input Sequence = NM_002759. Cut Site = UH/. Arm Length = 8. Core Sequence = CUGAUGAG GCCGUUAGGC CGAA NM_002759 (Homo sapiens protein kinase, interferon-inducible double stranded RNA dependent (PRKR), mRNA.; 2808 bp) Underlined region can be any X sequence or linker, as described herein.

[0271] TABLE-US-00009 TABLE IX Human PKR Inozyme and Substrate Sequence Seq Seq Pos Substrate ID Inozyme ID 17 GGCGGCGC A GUUUGCUC 1263 GAGCAAAC CUGAUGAGGCCGUUAGGCCGAA ICGCCGCC 1762 24 CAGUUUGC U CAUACUUU 1264 AAAGUAUG CUGAUGAGGCCGUUAGGCCGAA ICAAACUG 1763 26 GUUUGCUC A UACUUUGU 1265 ACAAAGUA CUGAUGAGGCCGUUAGGCCGAA IAGCAAAC 1764 30 GCUCAUAC U UUGUGACU 1266 AGUCACAA CUGAUGAGGCCGUUAGGCCGAA IUAUGAGC 1765 38 UUUGUGAC U UGCGGUCA 1267 UGACCGCA CUGAUGAGGCCGUUAGGCCGAA IUCACAAA 1766 46 UUGCGGUC A CAGUGGCA 1268 UGCCACUG CUGAUGAGGCCGUUAGGCCGAA IACCGCAA 1767 48 GCGGUCAC A GUGGCAUU 1269 AAUGCCAC CUGAUGAGGCCGUUAGGCCGAA IUGACCGC 1768 54 ACAGUGGC A UUCAGCUC 1270 GAGCUGAA CUGAUGAGGCCGUUAGGCCGAA ICCACUGU 1769 58 UGGCAUUC A GCUCCACA 1271 UGUGGAGC CUGAUGAGGCCGUUAGGCCGAA IAAUGCCA 1770 61 CAUUCAGC U CCACACUU 1272 AAGUGUGG CUGAUGAGGCCGUUAGGCCGAA ICUGAAUG 1771 63 UUCAGCUC C ACACUUGG 1273 CCAAGUGU CUGAUGAGGCCGUUAGGCCGAA IAGCUGAA 1772 64 UCAGCUCC A CACUUGGU 1274 ACCAAGUG CUGAUGAGGCCGUUAGGCCGAA IGAGCUGA 1773 66 AGCUCCAC A CUUGGUAG 1275 CUACCAAG CUGAUGAGGCCGUUAGGCCGAA IUGGAGCU 1774 68 CUCCACAC U UGGUAGAA 1276 UUCUACCA CUGAUGAGGCCGUUAGGCCGAA IUGUGGAG 1775 78 GGUAGAAC C ACAGGCAC 1277 GUGCCUGU CUGAUGAGGCCGUUAGGCCGAA IUUCUACC 1776 79 GUAGAACC A CAGGCACG 1278 CGUGCCUG CUGAUGAGGCCGUUAGGCCGAA IGUUCUAC 1777 81 AGAACCAC A GGCACGAC 1279 GUCGUGCC CUGAUGAGGCCGUUAGGCCGAA IUGGUUCU 1778 85 CCACAGGC A CGACAAGC 1280 GCUUGUCG CUGAUGAGGCCGUUAGGCCGAA ICCUGUGG 1779 90 GGCACGAC A AGCAUAGA 1281 UCUAUGCU CUGAUGAGGCCGUUAGGCCGAA IUCGUGCC 1780 94 CGACAAGC A UAGAAACA 1282 UGUUUCUA CUGAUGAGGCCGUUAGGCCGAA ICUUGUCG 1781 102 AUAGAAAC A UCCUAAAC 1283 GUUUAGGA CUGAUGAGGCCGUUAGGCCGAA IUUUCUAU 1782 105 GAAACAUC C UAAACAAU 1284 AUUGUUUA CUGAUGAGGCCGUUAGGCCGAA IAUGUUUC 1783 106 AAACAUCC U AAACAAUC 1285 GAUUGUUU CUGAUGAGGCCGUUAGGCCGAA IGAUGUUU 1784 111 UCCUAAAC A AUCUUCAU 1286 AUGAAGAU CUGAUGAGGCCGUUAGGCCGAA IUUUAGGA 1785 115 AAACAAUC U UCAUCGAG 1287 CUCGAUGA CUGAUGAGGCCGUUAGGCCGAA IAUUGUUU 1786 118 CAAUCUUC A UCGAGGCA 1288 UGCCUCGA CUGAUGAGGCCGUUAGGCCGAA IAAGAUUG 1787 126 AUCGAGGC A UCGAGGUC 1289 GACCUCGA CUGAUGAGGCCGUUAGGCCGAA ICCUCGAU 1788 135 UCGAGGUC C AUCCCAAU 1290 AUUGGGAU CUGAUGAGGCCGUUAGGCCGAA IACCUCGA 1789 136 CGAGGUCC A UCCCAAUA 1291 UAUUGGGA CUGAUGAGGCCGUUAGGCCGAA IGACCUCG 1790 139 GGUCCAUC C CAAUAAAA 1292 UUUUAUUG CUGAUGAGGCCGUUAGGCCGAA IAUGGACC 1791 140 GUCCAUCC C AAUAAAAA 1293 UUUUUAUU CUGAUGAGGCCGUUAGGCCGAA IGAUGGAC 1792 141 UCCAUCCC A AUAAAAAU 1294 AUUUUUAU CUGAUGAGGCCGUUAGGCCGAA IGGAUGGA 1793 151 UAAAAAUC A GGAGACCC 1295 GGGUCUCC CUGAUGAGGCCGUUAGGCCGAA IAUUUUUA 1794 158 CAGGAGAC C CUGGCUAU 1296 AUAGCCAG CUGAUGAGGCCGUUAGGCCGAA IUCUCCUG 1795 159 AGGAGACC C UGGCUAUC 1297 GAUAGCCA CUGAUGAGGCCGUUAGGCCGAA IGUCUCCU 1796 160 GGAGACCC U GGCUAUCA 1298 UGAUAGCC CUGAUGAGGCCGUUAGGCCGAA IGGUCUCC 1797 164 ACCCUGGC U AUCAUAGA 1299 UCUAUGAU CUGAUGAGGCCGUUAGGCCGAA ICCAGGGU 1798 168 UGGCUAUC A UAGACCUU 1300 AAGGUCUA CUGAUGAGGCCGUUAGGCCGAA IAUAGCCA 1799 174 UCAUAGAC C UUAGUCUU 1301 AAGACUAA CUGAUGAGGCCGUUAGGCCGAA IUCUAUGA 1800 175 CAUAGACC U UAGUCUUC 1302 GAAGACUA CUGAUGAGGCCGUUAGGCCGAA IGUCUAUG 1801 181 CCUUAGUC U UCGCUGGU 1303 ACCAGCGA CUGAUGAGGCCGUUAGGCCGAA IACUAAGG 1802 186 GUCUUCGC U GGUAUACU 1304 AGUAUACC CUGAUGAGGCCGUUAGGCCGAA ICGAAGAC 1803 194 UGGUAUAC U CGCUGUCU 1305 AGACAGCG CUGAUGAGGCCGUUAGGCCGAA IUAUACCA 1804 198 AUACUCGC U GUCUGUCA 1306 UGACAGAC CUGAUGAGGCCGUUAGGCCGAA ICGAGUAU 1805 202 UCGCUGUC U GUCAACCA 1307 UGGUUGAC CUGAUGAGGCCGUUAGGCCGAA IACAGCGA 1806 206 UGUCUGUC A ACCAGCGG 1308 CCGCUGGU CUGAUGAGGCCGUUAGGCCGAA IACAGACA 1807 209 CUGUCAAC C AGCGGUUG 1309 CAACCGCU CUGAUGAGGCCGUUAGGCCGAA IUUGACAG 1808 210 UGUCAACC A GCGGUUGA 1310 UCAACCGC CUGAUGAGGCCGUUAGGCCGAA IGUUGACA 1809 220 CGGUUGAC U UUUUUUAA 1311 UUAAAAAA CUGAUGAGGCCGUUAGGCCGAA IUCAACCG 1810 231 UUUUAAGC C UUCUUUUU 1312 AAAAAGAA CUGAUGAGGCCGUUAGGCCGAA ICUUAAAA 1811 232 UUUAAGCC U UCUUUUUU 1313 AAAAAAGA CUGAUGAGGCCGUUAGGCCGAA IGCUUAAA 1812 235 AAGCCUUC U UUUUUCUC 1314 GAGAAAAA CUGAUGAGGCCGUUAGGCCGAA IAAGGCUU 1813 242 CUUUUUUC U CUUUUACC 1315 GGUAAAAG CUGAUGAGGCCGUUAGGCCGAA IAAAAAAG 1814 244 UUUUUCUC U UUUACCAG 1316 CUGGUAAA CUGAUGAGGCCGUUAGGCCGAA IAGAAAAA 1815 250 UCUUUUAC C AGUUUCUG 1317 CAGAAACU CUGAUGAGGCCGUUAGGCCGAA IUAAAAGA 1816 251 CUUUUACC A GUUUCUGG 1318 CCAGAAAC CUGAUGAGGCCGUUAGGCCGAA IGUAAAAG 1817 257 CCAGUUUC U GGAGCAAA 1319 UUUGCUCC CUGAUGAGGCCGUUAGGCCGAA IAAACUGG 1818 263 UCUGGAGC A AAUUCAGU 1320 ACUGAAUU CUGAUGAGGCCGUUAGGCCGAA ICUCCAGA 1819 269 GCAAAUUC A GUUUGCCU 1321 AGGCAAAC CUGAUGAGGCCGUUAGGCCGAA IAAUUUGC 1820 276 CAGUUUGC C UUCCUGGA 1322 UCCAGGAA CUGAUGAGGCCGUUAGGCCGAA ICAAACUG 1821 277 AGUUUGCC U UCCUGGAU 1323 AUCCAGGA CUGAUGAGGCCGUUAGGCCGAA IGCAAACU 1822 280 UUGCCUUC C UGGAUUUG 1324 CAAAUCCA CUGAUGAGGCCGUUAGGCCGAA IAAGGCAA 1823 281 UGCCUUCC U GGAUUUGU 1325 ACAAAUCC CUGAUGAGGCCGUUAGGCCGAA IGAAGGCA 1824 303 GUAAUGAC C UCAAAACU 1326 AGUUUUGA CUGAUGAGGCCGUUAGGCCGAA IUCAUUAC 1825 304 UAAUGACC U CAAAACUU 1327 AAGUUUUG CUGAUGAGGCCGUUAGGCCGAA IGUCAUUA 1826 306 AUGACCUC A AAACUUUA 1328 UAAAGUUU CUGAUGAGGCCGUUAGGCCGAA IAGGUCAU 1827 311 CUCAAAAC U UUAGCAGU 1329 ACUGCUAA CUGAUGAGGCCGUUAGGCCGAA IUUUUGAG 1828 317 ACUUUAGC A GUUCUUCC 1330 GGAAGAAC CUGAUGAGGCCGUUAGGCCGAA ICUAAAGU 1829 322 AGCAGUUC U UCCAUCUG 1331 CAGAUGGA CUGAUGAGGCCGUUAGGCCGAA IAACUGCU 1830 325 AGUUCUUC C AUCUGACU 1332 AGUCAGAU CUGAUGAGGCCGUUAGGCCGAA IAAGAACU 1831 326 GUUCUUCC A UCUGACUC 1333 GAGUCAGA CUGAUGAGGCCGUUAGGCCGAA IGAAGAAC 1832 329 CUUCCAUC U GACUCAGG 1334 CCUGAGUC CUGAUGAGGCCGUUAGGCCGAA IAUGGAAG 1833 333 CAUCUGAC U CAGGUUUG 1335 CAAACCUG CUGAUGAGGCCGUUAGGCCGAA IUCAGAUG 1834 335 UCUGACUC A GGUUUGCU 1336 AGCAAACC CUGAUGAGGCCGUUAGGCCGAA IAGUCAGA 1835 343 AGGUUUGC U UCUCUGGC 1337 GCCAGAGA CUGAUGAGGCCGUUAGGCCGAA ICAAACCU 1836 346 UUUGCUUC U CUGGCGGU 1338 ACCGCCAG CUGAUGAGGCCGUUAGGCCGAA IAAGCAAA 1837 348 UGCUUCUC U GGCGGUCU 1339 AGACCGCC CUGAUGAGGCCGUUAGGCCGAA IAGAAGCA 1838 356 UGGCGGUC U UCAGAAUC 1340 GAUUCUGA CUGAUGAGGCCGUUAGGCCGAA IACCGCCA 1839 359 CGGUCUUC A GAAUCAAC 1341 GUUGAUUC CUGAUGAGGCCGUUAGGCCGAA IAAGACCG 1840 365 UCAGAAUC A ACAUCCAC 1342 GUGGAUGU CUGAUGAGGCCGUUAGGCCGAA IAUUCUGA 1841 368 GAAUCAAC A UCCACACU 1343 AGUGUGGA CUGAUGAGGCCGUUAGGCCGAA IUUGAUUC 1842 371 UCAACAUC C ACACUUCC 1344 GGAAGUGU CUGAUGAGGCCGUUAGGCCGAA IAUGUUGA 1843 372 CAACAUCC A CACUUCCG 1345 CGGAAGUG CUGAUGAGGCCGUUAGGCCGAA IGAUGUUG 1844 374 ACAUCCAC A CUUCCGUG 1346 CACGGAAG CUGAUGAGGCCGUUAGGCCGAA IUGGAUGU 1845 376 AUCCACAC U UCCGUGAU 1347 AUCACGGA CUGAUGAGGCCGUUAGGCCGAA IUGUGGAU 1846 379 CACACUUC C GUGAUUAU 1348 AUAAUCAC CUGAUGAGGCCGUUAGGCCGAA IAAGUGUG 1847 389 UGAUUAUC U GCGUGCAU 1349 AUGCACGC CUGAUGAGGCCGUUAGGCCGAA IAUAAUCA 1848 396 CUGCGUGC A UUUUGGAC 1350 GUCCAAAA CUGAUGAGGCCGUUAGGCCGAA ICACGCAG 1849

405 UUUUGGAC A AAGCUUCC 1351 GGAAGCUU CUGAUGAGGCCGUUAGGCCGAA IUCCAAAA 1850 410 GACAAAGC U UCCAACCA 1352 UGGUUGGA CUGAUGAGGCCGUUAGGCCGAA ICUUUGUC 1851 413 AAAGCUUC C AACCAGGA 1353 UCCUGGUU CUGAUGAGGCCGUUAGGCCGAA IAAGCUUU 1852 414 AAGCUUCC A ACCAGGAU 1354 AUCCUGGU CUGAUGAGGCCGUUAGGCCGAA IGAAGCUU 1853 417 CUUCCAAC C AGGAUACG 1355 CGUAUCCU CUGAUGAGGCCGUUAGGCCGAA IUUGGAAG 1854 418 UUCCAACC A GGAUACGG 1356 CCGUAUCC CUGAUGAGGCCGUUAGGCCGAA IGUUGGAA 1855 441 GAAAUGGC U GGUGAUCU 1357 AGAUCACC CUGAUGAGGCCGUUAGGCCGAA ICCAUUUC 1856 449 UGGUGAUC U UUCAGCAG 1358 CUGCUGAA CUGAUGAGGCCGUUAGGCCGAA IAUCACCA 1857 453 GAUCUUUC A GCAGGUUU 1359 AAACCUGC CUGAUGAGGCCGUUAGGCCGAA IAAAGAUC 1858 456 CUUUCAGC A GGUUUCUU 1360 AAGAAACC CUGAUGAGGCCGUUAGGCCGAA ICUGAAAG 1859 463 CAGGUUUC U UCAUGGAG 1361 CUCCAUGA CUGAUGAGGCCGUUAGGCCGAA IAAACCUG 1860 466 GUUUCUUC A UGGAGGAA 1362 UUCCUCCA CUGAUGAGGCCGUUAGGCCGAA IAAGAAAC 1861 476 GGAGGAAC U UAAUACAU 1363 AUGUAUUA CUGAUGAGGCCGUUAGGCCGAA IUUCCUCC 1862 483 CUUAAUAC A UACCGUCA 1364 UGACGGUA CUGAUGAGGCCGUUAGGCCGAA IUAUUAAG 1863 487 AUACAUAC C GUCAGAAG 1365 CUUCUGAC CUGAUGAGGCCGUUAGGCCGAA IUAUGUAU 1864 491 AUACCGUC A GAAGCAGG 1366 CCUGCUUC CUGAUGAGGCCGUUAGGCCGAA IACGGUAU 1865 497 UCAGAAGC A GGGAGUAG 1367 CUACUCCC CUGAUGAGGCCGUUAGGCCGAA ICUUCUGA 1866 509 AGUAGUAC U UAAAUAUC 1368 GAUAUUUA CUGAUGAGGCCGUUAGGCCGAA IUACUACU 1867 518 UAAAUAUC A AGAACUGC 1369 GCAGUUCU CUGAUGAGGCCGUUAGGCCGAA IAUAUUUA 1868 524 UCAAGAAC U GCCUAAUU 1370 AAUUAGGC CUGAUGAGGCCGUUAGGCCGAA IUUCUUGA 1869 527 AGAACUGC C UAAUUCAG 1371 CUGAAUUA CUGAUGAGGCCGUUAGGCCGAA ICAGUUCU 1870 528 GAACUGCC U AAUUCAGG 1372 CCUGAAUU CUGAUGAGGCCGUUAGGCCGAA IGCAGUUC 1871 534 CCUAAUUC A GGACCUCC 1373 GGAGGUCC CUGAUGAGGCCGUUAGGCCGAA IAAUUAGG 1872 539 UUCAGGAC C UCCACAUG 1374 CAUGUGGA CUGAUGAGGCCGUUAGGCCGAA IUCCUGAA 1873 540 UCAGGACC U CCACAUGA 1375 UCAUGUGG CUGAUGAGGCCGUUAGGCCGAA IGUCCUGA 1874 542 AGGACCUC C ACAUGAUA 1376 UAUCAUGU CUGAUGAGGCCGUUAGGCCGAA IAGGUCCU 1875 543 GGACCUCC A CAUGAUAG 1377 CUAUCAUG CUGAUGAGGCCGUUAGGCCGAA IGAGGUCC 1876 545 ACCUCCAC A UGAUAGGA 1378 UCCUAUCA CUGAUGAGGCCGUUAGGCCGAA IUGGAGGU 1877 561 AGGUUUAC A UUUCAAGU 1379 ACUUGAAA CUGAUGAGGCCGUUAGGCCGAA IUAAACCU 1878 566 UACAUUUC A AGUUAUAA 1380 UUAUAACU CUGAUGAGGCCGUUAGGCCGAA IAAAUGUA 1879 593 AGAAUUUC C AGAAGGUG 1381 CACCUUCU CUGAUGAGGCCGUUAGGCCGAA IAAAUUCU 1880 594 GAAUUUCC A GAAGGUGA 1382 UCACCUUC CUGAUGAGGCCGUUAGGCCGAA IGAAAUUC 1881 612 GGUAGAUC A AAGAAGGA 1383 UCCUUCUU CUGAUGAGGCCGUUAGGCCGAA IAUCUACC 1882 624 AAGGAAGC A AAAAAUGC 1384 GCAUUUUU CUGAUGAGGCCGUUAGGCCGAA ICUUCCUU 1883 633 AAAAAUGC C GCAGCCAA 1385 UUGGCUGC CUGAUGAGGCCGUUAGGCCGAA ICAUUUUU 1884 636 AAUGCCGC A GCCAAAUU 1386 AAUUUGGC CUGAUGAGGCCGUUAGGCCGAA ICGGCAUU 1885 639 GCCGCAGC C AAAUUAGC 1387 GCUAAUUU CUGAUGAGGCCGUUAGGCCGAA ICUGCGGC 1886 640 CCGCAGCC A AAUUAGCU 1388 AGCUAAUU CUGAUGAGGCCGUUAGGCCGAA IGCUGCGG 1887 648 AAAUUAGC U GUUGAGAU 1389 AUCUCAAC CUGAUGAGGCCGUUAGGCCGAA ICUAAUUU 1888 659 UGAGAUAC U UAAUAAGG 1390 CCUUAUUA CUGAUGAGGCCGUUAGGCCGAA IUAUCUCA 1889 678 AAGAAGGC A GUUAGUCC 1391 GGACUAAC CUGAUGAGGCCGUUAGGCCGAA ICCUUCUU 1890 686 AGUUAGUC C UUUAUUAU 1392 AUAAUAAA CUGAUGAGGCCGUUAGGCCGAA IACUAACU 1891 687 GUUAGUCC U UUAUUAUU 1393 AAUAAUAA CUGAUGAGGCCGUUAGGCCGAA IGACUAAC 1892 699 UUAUUGAC A ACAACGAA 1394 UUCGUUGU CUGAUGAGGCCGUUAGGCCGAA IUCAAUAA 1893 702 UUGACAAC A ACGAAUUC 1395 GAAUUCGU CUGAUGAGGCCGUUAGGCCGAA IUUGUCAA 1894 711 ACGAAUUC U UCAGAAGG 1396 CCUUCUGA CUGAUGAGGCCGUUAGGCCGAA IAAUUCGU 1895 714 AAUUCUUC A GAAGGAUU 1397 AAUCCUUC CUGAUGAGGCCGUUAGGCCGAA IAAGAAUU 1896 726 GGAUUAUC C AUGGGGAA 1398 UUCCCCAU CUGAUGAGGCCGUUAGGCCGAA IAUAAUCC 1897 727 GAUUAUCC A UGGGGAAU 1399 AUUCCCCA CUGAUGAGGCCGUUAGGCCGAA IGAUAAUC 1898 739 GGAAUUAC A UAGGCCUU 1400 AAGGCCUA CUGAUGAGGCCGUUAGGCCGAA IUAAUUCC 1899 745 ACAUAGGC C UUAUCAAU 1401 AUUGAUAA CUGAUGAGGCCGUUAGGCCGAA ICCUAUGU 1900 746 CAUAGGCC U UAUCAAUA 1402 UAUUGAUA CUGAUGAGGCCGUUAGGCCGAA IGCCUAUG 1901 751 GCCUUAUC A AUAGAAUU 1403 AAUUCUAU CUGAUGAGGCCGUUAGGCCGAA IAUAAGGC 1902 762 AGAAUUGC C CAGAAGAA 1404 UUCUUCUG CUGAUGAGGCCGUUAGGCCGAA ICAAUUCU 1903 763 GAAUUGCC C AGAAGAAA 1405 UUUCUUCU CUGAUGAGGCCGUUAGGCCGAA IGCAAUUC 1904 764 AAUUGCCC A GAAGAAAA 1406 UUUUCUUC CUGAUGAGGCCGUUAGGCCGAA IGGCAAUU 1905 776 GAAAAGAC U AACUGUAA 1407 UUACAGUU CUGAUGAGGCCGUUAGGCCGAA IUCUUUUC 1906 780 AGACUAAC U GUAAAUUA 1408 UAAUUUAC CUGAUGAGGCCGUUAGGCCGAA IUUAGUCU 1907 794 UUAUGAAC A GUGUGCAU 1409 AUGCACAC CUGAUGAGGCCGUUAGGCCGAA IUUCAUAA 1908 801 CAGUGUGC A UCGGGGGU 1410 ACCCCCGA CUGAUGAGGCCGUUAGGCCGAA ICACACUG 1909 812 GGGGGUGC A UGGGCCAG 1411 CUGGCCCA CUGAUGAGGCCGUUAGGCCGAA ICACCCCC 1910 818 GCAUGGGC C AGAAGGAU 1412 AUCCUUCU CUGAUGAGGCCGUUAGGCCGAA ICCCAUGC 1911 819 CAUGGGCC A GAAGGAUU 1413 AAUCCUUC CUGAUGAGGCCGUUAGGCCGAA IGCCCAUG 1912 830 AGGAUUUC A UUAUAAAU 1414 AUUUAUAA CUGAUGAGGCCGUUAGGCCGAA IAAAUCCU 1913 841 AUAAAUGC A AAAUGGGA 1415 UCCCAUUU CUGAUGAGGCCGUUAGGCCGAA ICAUUUAU 1914 851 AAUGGGAC A GAAAGAAU 1416 AUUCUUUC CUGAUGAGGCCGUUAGGCCGAA IUCCCAUU 1915 873 AUUGGUAC A GGUUCUAC 1417 GUAGAACC CUGAUGAGGCCGUUAGGCCGAA IUACCAAU 1916 879 ACAGGUUC U ACUAAACA 1418 UGUUUAGU CUGAUGAGGCCGUUAGGCCGAA IAACCUGU 1917 882 GGUUCUAC U AAACAGGA 1419 UCCUGUUU CUGAUGAGGCCGUUAGGCCGAA IUAGAACC 1918 887 UACUAAAC A GGAAGCAA 1420 UUGCUUCC CUGAUGAGGCCGUUAGGCCGAA IUUUAGUA 1919 894 CAGGAAGC A AAACAAUU 1421 AAUUGUUU CUGAUGAGGCCGUUAGGCCGAA ICUUCCUG 1920 899 AGCAAAAC A AUUGGCCG 1422 CGGCCAAU CUGAUGAGGCCGUUAGGCCGAA IUUUUGCU 1921 906 CAAUUGGC C GCUAAACU 1423 AGUUUAGC CUGAUGAGGCCGUUAGGCCGAA ICCAAUUG 1922 909 UUGGCCGC U AAACUUGC 1424 GCAAGUUU CUGAUGAGGCCGUUAGGCCGAA ICGGCCAA 1923 914 CGCUAAAC U UGCAUAUC 1425 GAUAUGCA CUGAUGAGGCCGUUAGGCCGAA IUUUAGCG 1924 918 AAACUUGC A UAUCUUCA 1426 UGAAGAUA CUGAUGAGGCCGUUAGGCCGAA ICAAGUUU 1925 923 UGCAUAUC U UCAGAUAU 1427 AUAUCUGA CUGAUGAGGCCGUUAGGCCGAA IAUAUGCA 1926 926 AUAUCUUC A GAUAUUAU 1428 AUAAUAUC CUGAUGAGGCCGUUAGGCCGAA IAAGAUAU 1927 936 AUAUUAUC A GAAGAAAC 1429 GUUUCUUC CUGAUGAGGCCGUUAGGCCGAA IAUAAUAU 1928 945 GAAGAAAC C UCAGUGAA 1430 UUCACUGA CUGAUGAGGCCGUUAGGCCGAA IUUUCUUC 1929 946 AAGAAACC U CAGUGAAA 1431 UUUCACUG CUGAUGAGGCCGUUAGGCCGAA IGUUUCUU 1930 948 GAAACCUC A GUGAAAUC 1432 GAUUUCAC CUGAUGAGGCCGUUAGGCCGAA IAGGUUUC 1931 957 GUGAAAUC U GACUACCU 1433 AGGUAGUC CUGAUGAGGCCGUUAGGCCGAA IAUUUCAC 1932

961 AAUCUGAC U ACCUGUCC 1434 GGACAGGU CUGAUGAGGCCGUUAGGCCGAA IUCAGAUU 1933 964 CUGACUAC C UGUCCUCU 1435 AGAGGACA CUGAUGAGGCCGUUAGGCCGAA IUAGUCAG 1934 965 UGACUACC U GUCCUCUG 1436 CAGAGGAC CUGAUGAGGCCGUUAGGCCGAA IGUAGUCA 1935 969 UACCUGUC C UCUGGUUC 1437 GAACCAGA CUGAUGAGGCCGUUAGGCCGAA IACAGGUA 1936 970 ACCUGUCC U CUGGUUCU 1438 AGAACCAG CUGAUGAGGCCGUUAGGCCGAA IGACAGGU 1937 972 CUGUCCUC U GGUUCUUU 1439 AAAGAACC CUGAUGAGGCCGUUAGGCCGAA IAGGACAG 1938 978 UCUGGUUC U UUUGCUAC 1440 GUAGCAAA CUGAUGAGGCCGUUAGGCCGAA IAACCAGA 1939 984 UCUUUUGC U ACUACGUG 1441 CACGUAGU CUGAUGAGGCCGUUAGGCCGAA ICAAAAGA 1940 987 UUUGCUAC U ACGUGUGA 1442 UCACACGU CUGAUGAGGCCGUUAGGCCGAA IUAGCAAA 1941 999 UGUGAGUC C CAAAGCAA 1443 UUGCUUUG CUGAUGAGGCCGUUAGGCCGAA IACUCACA 1942 1000 GUGAGUCC C AAAGCAAC 1444 GUUGCUUU CUGAUGAGGCCGUUAGGCCGAA IGACUCAC 1943 1001 UGAGUCCC A AAGCAACU 1445 AGUUGCUU CUGAUGAGGCCGUUAGGCCGAA IGGACUCA 1944 1006 CCCAAAGC A ACUCUUUA 1446 UAAAGAGU CUGAUGAGGCCGUUAGGCCGAA ICUUUGGG 1945 1009 AAAGCAAC U CUUUAGUG 1447 CACUAAAG CUGAUGAGGCCGUUAGGCCGAA IUUGCUUU 1946 1011 AGCAACUC U UUAGUGAC 1448 GUCACUAA CUGAUGAGGCCGUUAGGCCGAA IAGUUGCU 1947 1020 UUAGUGAC C AGCACACU 1449 AGUGUGCU CUGAUGAGGCCGUUAGGCCGAA IUCACUAA 1948 1021 UAGUGACC A GCACACUC 1450 GAGUGUGC CUGAUGAGGCCGUUAGGCCGAA IGUCACUA 1949 1024 UGACCAGC A CACUCGCU 1451 AGCGAGUG CUGAUGAGGCCGUUAGGCCGAA ICUGGUCA 1950 1026 ACCAGCAC A CUCGCUUC 1452 GAAGCGAG CUGAUGAGGCCGUUAGGCCGAA IUGCUGGU 1951 1028 CAGCACAC U CGCUUCUG 1453 CAGAAGCG CUGAUGAGGCCGUUAGGCCGAA IUGUGCUG 1952 1032 ACACUCGC U UCUGAAUC 1454 GAUUCAGA CUGAUGAGGCCGUUAGGCCGAA ICGAGUGU 1953 1035 CUCGCUUC U GAAUCAUC 1455 GAUGAUUC CUGAUGAGGCCGUUAGGCCGAA IAAGCGAG 1954 1041 UCUGAAUC A UCAUCUGA 1456 UCAGAUGA CUGAUGAGGCCGUUAGGCCGAA IAUUCAGA 1955 1044 GAAUCAUC A UCUGAAGG 1457 CCUUCAGA CUGAUGAGGCCGUUAGGCCGAA IAUGAUUC 1956 1047 UCAUCAUC U GAAGGUGA 1458 UCACCUUC CUGAUGAGGCCGUUAGGCCGAA IAUGAUGA 1957 1057 AAGGUGAC U UCUCAGCA 1459 UGCUGAGA CUGAUGAGGCCGUUAGGCCGAA IUCACCUU 1958 1060 GUGACUUC U CAGCAGAU 1460 AUCUGCUG CUGAUGAGGCCGUUAGGCCGAA IAAGUCAC 1959 1062 GACUUCUC A GCAGAUAC 1461 GUAUCUGC CUGAUGAGGCCGUUAGGCCGAA IAGAAGUC 1960 1065 UUCUCAGC A GAUACAUC 1462 GAUGUAUC CUGAUGAGGCCGUUAGGCCGAA ICUGAGAA 1961 1071 GCAGAUAC A UCAGAGAU 1463 AUCUCUGA CUGAUGAGGCCGUUAGGCCGAA IUAUCUGC 1962 1074 GAUACAUC A GAGAUAAA 1464 UUUAUCUC CUGAUGAGGCCGUUAGGCCGAA IAUGUAUC 1963 1086 AUAAAUUC U AACAGUGA 1465 UCACUGUU CUGAUGAGGCCGUUAGGCCGAA IAAUUUAU 1964 1090 AUUCUAAC A GUGACAGU 1466 ACUGUCAC CUGAUGAGGCCGUUAGGCCGAA IUUAGAAU 1965 1096 ACAGUGAC A GUUUAAAC 1467 GUUUAAAC CUGAUGAGGCCGUUAGGCCGAA IUCACUGU 1966 1105 GUUUAAAC A GUUCUUCG 1468 CGAAGAAC CUGAUGAGGCCGUUAGGCCGAA IUUUAAAC 1967 1110 AACAGUUC U UCGUUGCU 1469 AGCAACGA CUGAUGAGGCCGUUAGGCCGAA IAACUGUU 1968 1118 UUCGUUGC U UAUGAAUG 1470 CAUUCAUA CUGAUGAGGCCGUUAGGCCGAA ICAACGAA 1969 1130 GAAUGGUC U CAGAAAUA 1471 UAUUUCUG CUGAUGAGGCCGUUAGGCCGAA IACCAUUC 1970 1132 AUGGUCUC A GAAAUAAU 1472 AUUAUUUC CUGAUGAGGCCGUUAGGCCGAA IAGACCAU 1971 1142 AAAUAAUC A AAGGAAGG 1473 CCUUCCUU CUGAUGAGGCCGUUAGGCCGAA IAUUAUUU 1972 1152 AGGAAGGC A AAAAGAUC 1474 GAUCUUUU CUGAUGAGGCCGUUAGGCCGAA ICCUUCCU 1973 1161 AAAAGAUC U UUGGCACC 1475 GGUGCCAA CUGAUGAGGCCGUUAGGCCGAA IAUCUUUU 1974 1167 UCUUUGGC A CCCAGAUU 1476 AAUCUGGG CUGAUGAGGCCGUUAGGCCGAA ICCAAAGA 1975 1169 UUUGGCAC C CAGAUUUG 1477 CAAAUCUG CUGAUGAGGCCGUUAGGCCGAA IUGCCAAA 1976 1170 UUGGCACC C AGAUUUGA 1478 UCAAAUCU CUGAUGAGGCCGUUAGGCCGAA IGUGCCAA 1977 1171 UGGCACCC A GAUUUGAC 1479 GUCAAAUC CUGAUGAGGCCGUUAGGCCGAA IGGUGCCA 1978 1180 GAUUUGAC C UUCCUGAC 1480 GUCAGGAA CUGAUGAGGCCGUUAGGCCGAA IUCAAAUC 1979 1181 AUUUGACC U UCCUGACA 1481 UGUCAGGA CUGAUGAGGCCGUUAGGCCGAA IGUCAAAU 1980 1184 UGACCUUC C UGACAUGA 1482 UCAUGUCA CUGAUGAGGCCGUUAGGCCGAA IAAGGUCA 1981 1185 GACCUUCC U GACAUGAA 1483 UUCAUGUC CUGAUGAGGCCGUUAGGCCGAA IGAAGGUC 1982 1189 UUCCUGAC A UGAAAGAA 1484 UUCUUUCA CUGAUGAGGCCGUUAGGCCGAA IUCAGGAA 1983 1200 AAAGAAAC A AAGUAUAC 1485 GUAUACUU CUGAUGAGGCCGUUAGGCCGAA IUUUCUUU 1984 1209 AAGUAUAC U GUGGACAA 1486 UUGUCCAC CUGAUGAGGCCGUUAGGCCGAA IUAUACUU 1985 1216 CUGUGGAC A AGAGGUUU 1487 AAACCUCU CUGAUGAGGCCGUUAGGCCGAA IUCCACAG 1986 1228 GGUUUGGC A UGGAUUUU 1488 AAAAUCCA CUGAUGAGGCCGUUAGGCCGAA ICCAAACC 1987 1258 UAAUUGGC U CAGGUGGA 1489 UCCACCUG CUGAUGAGGCCGUUAGGCCGAA ICCAAUUA 1988 1260 AUUGGCUC A GGUGGAUU 1490 AAUCCACC CUGAUGAGGCCGUUAGGCCGAA IAGCCAAU 1989 1273 GAUUUGGC C AAGUUUUC 1491 GAAAACUU CUGAUGAGGCCGUUAGGCCGAA ICCAAAUC 1990 1274 AUUUGGCC A AGUUUUCA 1492 UGAAAACU CUGAUGAGGCCGUUAGGCCGAA IGCCAAAU 1991 1282 AAGUUUUC A AAGCAAAA 1493 UUUUGCUU CUGAUGAGGCCGUUAGGCCGAA IAAAACUU 1992 1287 UUCAAAGC A AAACACAG 1494 CUGUGUUU CUGAUGAGGCCGUUAGGCCGAA ICUUUGAA 1993 1292 AGCAAAAC A CAGAAUUG 1495 CAAUUCUG CUGAUGAGGCCGUUAGGCCGAA IUUUUGCU 1994 1294 CAAAACAC A GAAUUGAC 1496 GUCAAUUC CUGAUGAGGCCGUUAGGCCGAA IUGUUUUG 1995 1311 GGAAAGAC U UACGUUAU 1497 AUAACGUA CUGAUGAGGCCGUUAGGCCGAA IUCUUUCC 1996 1368 GUAAAAGC A UUGGCAAA 1498 UUUGCCAA CUGAUGAGGCCGUUAGGCCGAA ICUUUUAC 1997 1374 GCAUUGGC A AAACUUGA 1499 UCAAGUUU CUGAUGAGGCCGUUAGGCCGAA ICCAAUGC 1998 1379 GGCAAAAC U UGAUCAUG 1500 CAUGAUCA CUGAUGAGGCCGUUAGGCCGAA IUUUUGCC 1999 1385 ACUUGAUC A UGUAAAUA 1501 UAUUUACA CUGAUGAGGCCGUUAGGCCGAA IAUCAAGU 2000 1400 UAUUGUUC A CUACAAUG 1502 CAUUGUAG CUGAUGAGGCCGUUAGGCCGAA IAACAAUA 2001 1402 UUGUUCAC U ACAAUGGC 1503 GCCAUUGU CUGAUGAGGCCGUUAGGCCGAA IUGAACAA 2002 1405 UUCACUAC A AUGGCUGU 1504 ACAGCCAU CUGAUGAGGCCGUUAGGCCGAA IUAGUGAA 2003 1411 ACAAUGGC U GUUGGGAU 1505 AUCCCAAC CUGAUGAGGCCGUUAGGCCGAA ICCAUUGU 2004 1436 UUAUGAUC C UGAGACCA 1506 UGGUCUCA CUGAUGAGGCCGUUAGGCCGAA IAUCAUAA 2005 1437 UAUGAUCC U GAGACCAG 1507 CUGGUCUC CUGAUGAGGCCGUUAGGCCGAA IGAUCAUA 2006 1443 CCUGAGAC C AGUGAUGA 1508 UCAUCACU CUGAUGAGGCCGUUAGGCCGAA IUCUCAGG 2007 1444 CUGAGACC A GUGAUGAU 1509 AUCAUCAC CUGAUGAGGCCGUUAGGCCGAA IGUCUCAG 2008 1455 GAUGAUUC U CUUGAGAG 1510 CUCUCAAG CUGAUGAGGCCGUUAGGCCGAA IAAUCAUC 2009 1457 UGAUUCUC U UGAGAGCA 1511 UGCUCUCA CUGAUGAGGCCGUUAGGCCGAA IAGAAUCA 2010 1465 UUGAGAGC A GUGAUUAU 1512 AUAAUCAC CUGAUGAGGCCGUUAGGCCGAA ICUCUCAA 2011 1478 UUAUGAUC C UGAGAACA 1513 UGUUCUCA CUGAUGAGGCCGUUAGGCCGAA IAUCAUAA 2012 1479 UAUGAUCC U GAGAACAG 1514 CUGUUCUC CUGAUGAGGCCGUUAGGCCGAA IGAUCAUA 2013 1486 CUGAGAAC A GCAAAAAU 1515 AUUUUUGC CUGAUGAGGCCGUUAGGCCGAA IUUCUCAG 2014 1489 AGAACAGC A AAAAUAGU 1516 ACUAUUUU CUGAUGAGGCCGUUAGGCCGAA ICUGUUCU 2015 1500 AAUAGUUC A AGGUCAAA 1517 UUUGACCU CUGAUGAGGCCGUUAGGCCGAA IAACUAUU 2016

1506 UCAAGGUC A AAGACUAA 1518 UUAGUCUU CUGAUGAGGCCGUUAGGCCGAA IACCUUGA 2017 1512 UCAAAGAC U AAGUGCCU 1519 AGGCACUU CUGAUGAGGCCGUUAGGCCGAA IUCUUUGA 2018 1519 CUAAGUGC C UUUUCAUC 1520 GAUGAAAA CUGAUGAGGCCGUUAGGCCGAA ICACUUAG 2019 1520 UAAGUGCC U UUUCAUCC 1521 GGAUGAAA CUGAUGAGGCCGUUAGGCCGAA IGCACUUA 2020 1525 GCCUUUUC A UCCAAAUG 1522 CAUUUGGA CUGAUGAGGCCGUUAGGCCGAA IAAAAGGC 2021 1528 UUUUCAUC C AAAUGGAA 1523 UUCCAUUU CUGAUGAGGCCGUUAGGCCGAA IAUGAAAA 2022 1529 UUUCAUCC A AAUGGAAU 1524 AUUCCAUU CUGAUGAGGCCGUUAGGCCGAA IGAUGAAA 2023 1540 UGGAAUUC U GUGAUAAA 1525 UUUAUCAC CUGAUGAGGCCGUUAGGCCGAA IAAUUCCA 2024 1554 AAAGGGAC C UUGGAACA 1526 UGUUCCAA CUGAUGAGGCCGUUAGGCCGAA IUCCCUUU 2025 1555 AAGGGACC U UGGAACAA 1527 UUGUUCCA CUGAUGAGGCCGUUAGGCCGAA IGUCCCUU 2026 1562 CUUGGAAC A AUGGAUUG 1528 CAAUCCAU CUGAUGAGGCCGUUAGGCCGAA IUUCCAAG 2027 1592 CGAGAAAC U AGACAAAG 1529 CUUUGUCU CUGAUGAGGCCGUUAGGCCGAA IUUUCUCG 2028 1597 AACUAGAC A AAGUUUUG 1530 CAAAACUU CUGAUGAGGCCGUUAGGCCGAA IUCUAGUU 2029 1608 GUUUUGGC U UUGGAACU 1531 AGUUCCAA CUGAUGAGGCCGUUAGGCCGAA ICCAAAAC 2030 1616 UUUGGAAC U CUUUGAAC 1532 GUUCAAAG CUGAUGAGGCCGUUAGGCCGAA IUUCCAAA 2031 1618 UGGAACUC U UUGAACAA 1533 UUGUUCAA CUGAUGAGGCCGUUAGGCCGAA IAGUUCCA 2032 1625 CUUUGAAC A AAUAACAA 1534 UUGUUAUU CUGAUGAGGCCGUUAGGCCGAA IUUCAAAG 2033 1632 CAAAUAAC A AAAGGGGU 1535 ACCCCUUU CUGAUGAGGCCGUUAGGCCGAA IUUAUUUG 2034 1652 UUAUAUAC A UUCAAAAA 1536 UUUUUGAA CUGAUGAGGCCGUUAGGCCGAA IUAUAUAA 2035 1656 AUACAUUC A AAAAAAUU 1537 AAUUUUUU CUGAUGAGGCCGUUAGGCCGAA IAAUGUAU 2036 1670 AUUAAUUC A UAGAGAUC 1538 GAUCUCUA CUGAUGAGGCCGUUAGGCCGAA IAAUUAAU 2037 1679 UAGAGAUC U UAAGCCAA 1539 UUGGCUUA CUGAUGAGGCCGUUAGGCCGAA IAUCUCUA 2038 1685 UCUUAAGC C AAGUAAUA 1540 UAUUACUU CUGAUGAGGCCGUUAGGCCGAA ICUUAAGA 2039 1686 CUUAAGCC A AGUAAUAU 1541 AUAUUACU CUGAUGAGGCCGUUAGGCCGAA IGCUUAAG 2040 1699 AUAUAUUC U UAGUAGAU 1542 AUCUACUA CUGAUGAGGCCGUUAGGCCGAA IAAUAUAU 2041 1710 GUAGAUAC A AAACAAGU 1543 ACUUGUUU CUGAUGAGGCCGUUAGGCCGAA IUAUCUAC 2042 1715 UACAAAAC A AGUAAAGA 1544 UCUUUACU CUGAUGAGGCCGUUAGGCCGAA IUUUUGUA 2043 1732 UUGGAGAC U UUGGACUU 1545 AAGUCCAA CUGAUGAGGCCGUUAGGCCGAA IUCUCCAA 2044 1739 CUUUGGAC U UGUAACAU 1546 AUGUUACA CUGAUGAGGCCGUUAGGCCGAA IUCCAAAG 2045 1746 CUUGUAAC A UCUCUGAA 1547 UUCAGAGA CUGAUGAGGCCGUUAGGCCGAA IUUACAAG 2046 1749 GUAACAUC U CUGAAAAA 1548 UUUUUCAG CUGAUGAGGCCGUUAGGCCGAA IAUGUUAC 2047 1751 AACAUCUC U GAAAAAUG 1549 CAUUUUUC CUGAUGAGGCCGUUAGGCCGAA IAGAUGUU 2048 1773 AAGCGAAC A AGGAGUAA 1550 UUACUCCU CUGAUGAGGCCGUUAGGCCGAA IUUCGCUU 2049 1788 AAGGGAAC U UUGCGAUA 1551 UAUCGCAA CUGAUGAGGCCGUUAGGCCGAA IUUCCCUU 2050 1798 UGCGAUAC A UGAGCCCA 1552 UGGGCUCA CUGAUGAGGCCGUUAGGCCGAA IUAUCGCA 2051 1804 ACAUGAGC C CAGAACAG 1553 CUGUUCUG CUGAUGAGGCCGUUAGGCCGAA ICUCAUGU 2052 1805 CAUGAGCC C AGAACAGA 1554 UCUGUUCU CUGAUGAGGCCGUUAGGCCGAA IGCUCAUG 2053 1806 AUGAGCCC A GAACAGAU 1555 AUCUGUUC CUGAUGAGGCCGUUAGGCCGAA IGGCUCAU 2054 1811 CCCAGAAC A GAUUUCUU 1556 AAGAAAUC CUGAUGAGGCCGUUAGGCCGAA IUUCUGGG 2055 1818 CAGAUUUC U UCGCAAGA 1557 UCUUGCGA CUGAUGAGGCCGUUAGGCCGAA IAAAUCUG 2056 1823 UUCUUCGC A AGACUAUG 1558 CAUAGUCU CUGAUGAGGCCGUUAGGCCGAA ICGAAGAA 2057 1828 CGCAAGAC U AUGGAAAG 1559 CUUUCCAU CUGAUGAGGCCGUUAGGCCGAA IUCUUGCG 2058 1846 AAGUGGAC C UCUACGCU 1560 AGCGUAGA CUGAUGAGGCCGUUAGGCCGAA IUCCACUU 2059 1847 AGUGGACC U CUACGCUU 1561 AAGCGUAG CUGAUGAGGCCGUUAGGCCGAA IGUCCACU 2060 1849 UGGACCUC U ACGCUUUG 1562 CAAAGCGU CUGAUGAGGCCGUUAGGCCGAA IAGGUCCA 2061 1854 CUCUACGC U UUGGGGCU 1563 AGCCCCAA CUGAUGAGGCCGUUAGGCCGAA ICGUAGAG 2062 1862 UUUGGGGC U AAUUCUUG 1564 CAAGAAUU CUGAUGAGGCCGUUAGGCCGAA ICCCCAAA 2063 1868 GCUAAUUC U UGCUGAAC 1565 GUUCAGCA CUGAUGAGGCCGUUAGGCCGAA IAAUUAGC 2064 1872 AUUCUUGC U GAACUUCU 1566 AGAAGUUC CUGAUGAGGCCGUUAGGCCGAA ICAAGAAU 2065 1877 UGCUGAAC U UCUUCAUG 1567 CAUGAAGA CUGAUGAGGCCGUUAGGCCGAA IUUCAGCA 2066 1880 UGAACUUC U UCAUGUAU 1568 AUACAUGA CUGAUGAGGCCGUUAGGCCGAA IAAGUUCA 2067 1883 ACUUCUUC A UGUAUGUG 1569 CACAUACA CUGAUGAGGCCGUUAGGCCGAA IAAGAAGU 2068 1894 UAUGUGAC A CUGCUUUU 1570 AAAAGCAG CUGAUGAGGCCGUUAGGCCGAA IUCACAUA 2069 1896 UGUGACAC U GCUUUUGA 1571 UCAAAAGC CUGAUGAGGCCGUUAGGCCGAA IUGUCACA 2070 1899 GACACUGC U UUUGAAAC 1572 GUUUCAAA CUGAUGAGGCCGUUAGGCCGAA ICAGUGUC 2071 1908 UUUGAAAC A UCAAAGUU 1573 AACUUUGA CUGAUGAGGCCGUUAGGCCGAA IUUUCAAA 2072 1911 GAAACAUC A AAGUUUUU 1574 AAAAACUU CUGAUGAGGCCGUUAGGCCGAA IAUGUUUC 2073 1921 AGUUUUUC A CAGACCUA 1575 UAGGUCUG CUGAUGAGGCCGUUAGGCCGAA IAAAAACU 2074 1923 UUUUUCAC A GACCUACG 1576 CGUAGGUC CUGAUGAGGCCGUUAGGCCGAA IUGAAAAA 2075 1927 UCACAGAC C UACGGGAU 1577 AUCCCGUA CUGAUGAGGCCGUUAGGCCGAA IUCUGUGA 2076 1928 CACAGACC U ACGGGAUG 1578 CAUCCCGU CUGAUGAGGCCGUUAGGCCGAA IGUCUGUG 2077 1939 GGGAUGGC A UCAUCUCA 1579 UGAGAUGA CUGAUGAGGCCGUUAGGCCGAA ICCAUCCC 2078 1942 AUGGCAUC A UCUCAGAU 1580 AUCUGAGA CUGAUGAGGCCGUUAGGCCGAA IAUGCCAU 2079 1945 GCAUCAUC U CAGAUAUA 1581 UAUAUCUG CUGAUGAGGCCGUUAGGCCGAA IAUGAUGC 2080 1947 AUCAUCUC A GAUAUAUU 1582 AAUAUAUC CUGAUGAGGCCGUUAGGCCGAA IAGAUGAU 2081 1974 GAAAAAAC U CUUCUACA 1583 UGUAGAAG CUGAUGAGGCCGUUAGGCCGAA IUUUUUUC 2082 1976 AAAAACUC U UCUACAGA 1584 UCUGUAGA CUGAUGAGGCCGUUAGGCCGAA IAGUUUUU 2083 1979 AACUCUUC U ACAGAAAU 1585 AUUUCUGU CUGAUGAGGCCGUUAGGCCGAA IAAGAGUU 2084 1982 UCUUCUAC A GAAAUUAC 1586 GUAAUUUC CUGAUGAGGCCGUUAGGCCGAA IUAGAAGA 2085 1991 GAAAUUAC U CUCAAAGA 1587 UCUUUGAG CUGAUGAGGCCGUUAGGCCGAA IUAAUUUC 2086 1993 AAUUACUC U CAAAGAAA 1588 UUUCUUUG CUGAUGAGGCCGUUAGGCCGAA IAGUAAUU 2087 1995 UUACUCUC A AAGAAACC 1589 GGUUUCUU CUGAUGAGGCCGUUAGGCCGAA IAGAGUAA 2088 2003 AAAGAAAC C UGAGGAUC 1590 GAUCCUCA CUGAUGAGGCCGUUAGGCCGAA IUUUCUUU 2089 2004 AAGAAACC U GAGGAUCG 1591 CGAUCCUC CUGAUGAGGCCGUUAGGCCGAA IGUUUCUU 2090 2015 GGAUCGAC C UAACACAU 1592 AUGUGUUA CUGAUGAGGCCGUUAGGCCGAA IUCGAUCC 2091 2016 GAUCGACC U AACACAUC 1593 GAUGUGUU CUGAUGAGGCCGUUAGGCCGAA IGUCGAUC 2092 2020 GACCUAAC A CAUCUGAA 1594 UUCAGAUG CUGAUGAGGCCGUUAGGCCGAA IUUAGGUC 2093 2022 CCUAACAC A UCUGAAAU 1595 AUUUCAGA CUGAUGAGGCCGUUAGGCCGAA IUGUUAGG 2094 2025 AACACAUC U GAAAUACU 1596 AGUAUUUC CUGAUGAGGCCGUUAGGCCGAA IAUGUGUU 2095 2033 UGAAAUAC U AAGGACCU 1597 AGGUCCUU CUGAUGAGGCCGUUAGGCCGAA IUAUUUCA 2096 2040 CUAAGGAC C UUGACUGU 1598 ACAGUCAA CUGAUGAGGCCGUUAGGCCGAA IUCCUUAG 2097 2041 UAAGGACC U UGACUGUG 1599 CACAGUCA CUGAUGAGGCCGUUAGGCCGAA IGUCCUUA 2098 2046 ACCUUGAC U GUGUGGAA 1600 UUCCACAC CUGAUGAGGCCGUUAGGCCGAA IUCAAGGU 2099 2062 AGAAAAGC C CAGAGAAA 1601 UUUCUCUG CUGAUGAGGCCGUUAGGCCGAA ICUUUUCU

2100 2063 GAAAAGCC C AGAGAAAA 1602 UUUUCUCU CUGAUGAGGCCGUUAGGCCGAA IGCUUUUC 2101 2064 AAAAGCCC A GAGAAAAA 1603 UUUUUCUC CUGAUGAGGCCGUUAGGCCGAA IGGCUUUU 2102 2081 UGAACGAC A CACAUGUU 1604 AACAUGUG CUGAUGAGGCCGUUAGGCCGAA IUCGUUCA 2103 2083 AACGACAC A CAUGUUAG 1605 CUAACAUG CUGAUGAGGCCGUUAGGCCGAA IUGUCGUU 2104 2085 CGACACAC A UGUUAGAG 1606 CUCUAACA CUGAUGAGGCCGUUAGGCCGAA IUGUGUCG 2105 2095 GUUAGAGC C CUUCUGAA 1607 UUCAGAAG CUGAUGAGGCCGUUAGGCCGAA ICUCUAAC 2106 2096 UUAGAGCC C UUCUGAAA 1608 UUUCAGAA CUGAUGAGGCCGUUAGGCCGAA IGCUCUAA 2107 2097 UAGAGCCC U UCUGAAAA 1609 UUUUCAGA CUGAUGAGGCCGUUAGGCCGAA IGGCUCUA 2108 2100 AGCCCUUC U GAAAAAGU 1610 ACUUUUUC CUGAUGAGGCCGUUAGGCCGAA IAAGGGCU 2109 2112 AAAGUAUC C UGCUUCUG 1611 CAGAAGCA CUGAUGAGGCCGUUAGGCCGAA IAUACUUU 2110 2113 AAGUAUCC U GCUUCUGA 1612 UCAGAAGC CUGAUGAGGCCGUUAGGCCGAA IGAUACUU 2111 2116 UAUCCUGC U UCUGAUAU 1613 AUAUCAGA CUGAUGAGGCCGUUAGGCCGAA ICAGGAUA 2112 2119 CCUGCUUC U GAUAUGCA 1614 UGCAUAUC CUGAUGAGGCCGUUAGGCCGAA IAAGCAGG 2113 2127 UGAUAUGC A GUUUUCCU 1615 AGGAAAAC CUGAUGAGGCCGUUAGGCCGAA ICAUAUCA 2114 2134 CAGUUUUC C UUAAAUUA 1616 UAAUUUAA CUGAUGAGGCCGUUAGGCCGAA IAAAACUG 2115 2135 AGUUUUCC U UAAAUUAU 1617 AUAAUUUA CUGAUGAGGCCGUUAGGCCGAA IGAAAACU 2116 2145 AAAUUAUC U AAAAUCUG 1618 CAGAUUUU CUGAUGAGGCCGUUAGGCCGAA IAUAAUUU 2117 2152 CUAAAAUC U GCUAGGGA 1619 UCCCUAGC CUGAUGAGGCCGUUAGGCCGAA IAUUUUAG 2118 2155 AAAUCUGC U AGGGAAUA 1620 UAUUCCCU CUGAUGAGGCCGUUAGGCCGAA ICAGAUUU 2119 2166 GGAAUAUC A AUAGAUAU 1621 AUAUCUAU CUGAUGAGGCCGUUAGGCCGAA IAUAUUCC 2120 2179 AUAUUUAC C UUUUAUUU 1622 AAAUAAAA CUGAUGAGGCCGUUAGGCCGAA IUAAAUAU 2121 2180 UAUUUACC U UUUAUUUU 1623 AAAAUAAA CUGAUGAGGCCGUUAGGCCGAA IGUAAAUA 2122 2197 AAUGUUUC C UUUAAUUU 1624 AAAUUAAA CUGAUGAGGCCGUUAGGCCGAA IAAACAUU 2123 2198 AUGUUUCC U UUAAUUUU 1625 AAAAUUAA CUGAUGAGGCCGUUAGGCCGAA IGAAACAU 2124 2211 UUUUUUAC U AUUUUUAC 1626 GUAAAAAU CUGAUGAGGCCGUUAGGCCGAA IUAAAAAA 2125 2220 AUUUUUAC U AAUCUUUC 1627 GAAAGAUU CUGAUGAGGCCGUUAGGCCGAA IUAAAAAU 2126 2225 UACUAAUC U UUCUGCAG 1628 CUGCAGAA CUGAUGAGGCCGUUAGGCCGAA IAUUAGUA 2127 2229 AAUCUUUC U GCAGAAAC 1629 GUUUCUGC CUGAUGAGGCCGUUAGGCCGAA IAAAGAUU 2128 2232 CUUUCUGC A GAAACAGA 1630 UCUGUUUC CUGAUGAGGCCGUUAGGCCGAA ICAGAAAG 2129 2238 GCAGAAAC A GAAAGGUU 1631 AACCUUUC CUGAUGAGGCCGUUAGGCCGAA IUUUCUGC 2130 2250 AGGUUUUC U UCUUUUUG 1632 CAAAAAGA CUGAUGAGGCCGUUAGGCCGAA IAAAACCU 2131 2253 UUUUCUUC U UUUUGCUU 1633 AAGCAAAA CUGAUGAGGCCGUUAGGCCGAA IAAGAAAA 2132 2260 CUUUUUGC U UCAAAAAC 1634 GUUUUUGA CUGAUGAGGCCGUUAGGCCGAA ICAAAAAG 2133 2263 UUUGCUUC A AAAACAUU 1635 AAUGUUUU CUGAUGAGGCCGUUAGGCCGAA IAAGCAAA 2134 2269 UCAAAAAC A UUCUUACA 1636 UGUAAGAA CUGAUGAGGCCGUUAGGCCGAA IUUUUUGA 2135 2273 AAACAUUC U UACAUUUU 1637 AAAAUGUA CUGAUGAGGCCGUUAGGCCGAA IAAUGUUU 2136 2277 AUUCUUAC A UUUUACUU 1638 AAGUAAAA CUGAUGAGGCCGUUAGGCCGAA IUAAGAAU 2137 2284 CAUUUUAC U UUUUCCUG 1639 CAGGAAAA CUGAUGAGGCCGUUAGGCCGAA IUAAAAUG 2138 2290 ACUUUUUC C UGGCUCAU 1640 AUGAGCCA CUGAUGAGGCCGUUAGGCCGAA IAAAAAGU 2139 2291 CUUUUUCC U GGCUCAUC 1641 GAUGAGCC CUGAUGAGGCCGUUAGGCCGAA IGAAAAAG 2140 2295 UUCCUGGC U CAUCUCUU 1642 AAGAGAUG CUGAUGAGGCCGUUAGGCCGAA ICCAGGAA 2141 2297 CCUGGCUC A UCUCUUUA 1643 UAAAGAGA CUGAUGAGGCCGUUAGGCCGAA IAGCCAGG 2142 2300 GGCUCAUC U CUUUAUUC 1644 GAAUAAAG CUGAUGAGGCCGUUAGGCCGAA IAUGAGCC 2143 2302 CUCAUCUC U UUAUUCUU 1645 AAGAAUAA CUGAUGAGGCCGUUAGGCCGAA IAGAUGAG 2144 2309 CUUUAUUC U UUUUUUUU 1646 AAAAAAAA CUGAUGAGGCCGUUAGGCCGAA IAAUAAAG 2145 2329 UUAAAGAC A GAGUCUCG 1647 CGAGACUC CUGAUGAGGCCGUUAGGCCGAA IUCUUUAA 2146 2335 ACAGAGUC U CGCUCUGU 1648 ACAGAGCG CUGAUGAGGCCGUUAGGCCGAA IACUCUGU 2147 2339 AGUCUCGC U CUGUUGCC 1649 GGCAACAG CUGAUGAGGCCGUUAGGCCGAA ICGAGACU 2148 2341 UCUCGCUC U GUUGCCCA 1650 UGGGCAAC CUGAUGAGGCCGUUAGGCCGAA IAGCGAGA 2149 2347 UCUGUUGC C CAGGCUGG 1651 CCAGCCUG CUGAUGAGGCCGUUAGGCCGAA ICAACAGA 2150 2348 CUGUUGCC C AGGCUGGA 1652 UCCAGCCU CUGAUGAGGCCGUUAGGCCGAA IGCAACAG 2151 2349 UGUUGCCC A GGCUGGAG 1653 CUCCAGCC CUGAUGAGGCCGUUAGGCCGAA IGGCAACA 2152 2353 GCCCAGGC U GGAGUGCA 1654 UGCACUCC CUGAUGAGGCCGUUAGGCCGAA ICCUGGGC 2153 2361 UGGAGUGC A AUGACACA 1655 UGUGUCAU CUGAUGAGGCCGUUAGGCCGAA ICACUCCA 2154 2367 GCAAUGAC A CAGUCUUG 1656 CAAGACUG CUGAUGAGGCCGUUAGGCCGAA IUCAUUGC 2155 2369 AAUGACAC A GUCUUGGC 1657 GCCAAGAC CUGAUGAGGCCGUUAGGCCGAA IUGUCAUU 2156 2373 ACACAGUC U UGGCUCAC 1658 GUGAGCCA CUGAUGAGGCCGUUAGGCCGAA IACUGUGU 2157 2378 GUCUUGGC U CACUGCAA 1659 UUGCAGUG CUGAUGAGGCCGUUAGGCCGAA ICCAAGAC 2158 2380 CUUGGCUC A CUGCAACU 1660 AGUUGCAG CUGAUGAGGCCGUUAGGCCGAA IAGCCAAG 2159 2382 UGGCUCAC U GCAACUUC 1661 GAAGUUGC CUGAUGAGGCCGUUAGGCCGAA IUGAGCCA 2160 2385 CUCACUGC A ACUUCUGC 1662 GCAGAAGU CUGAUGAGGCCGUUAGGCCGAA ICAGUGAG 2161 2388 ACUGCAAC U UCUGCCUC 1663 GAGGCAGA CUGAUGAGGCCGUUAGGCCGAA IUUGCAGU 2162 2391 GCAACUUC U GCCUCUUG 1664 CAAGAGGC CUGAUGAGGCCGUUAGGCCGAA IAAGUUGC 2163 2394 ACUUCUGC C UCUUGGGU 1665 ACCCAAGA CUGAUGAGGCCGUUAGGCCGAA ICAGAAGU 2164 2395 CUUCUGCC U CUUGGGUU 1666 AACCCAAG CUGAUGAGGCCGUUAGGCCGAA IGCAGAAG 2165 2397 UCUGCCUC U UGGGUUCA 1667 UGAACCCA CUGAUGAGGCCGUUAGGCCGAA IAGGCAGA 2166 2405 UUGGGUUC A AGUGAUUC 1668 GAAUCACU CUGAUGAGGCCGUUAGGCCGAA IAACCCAA 2167 2414 AGUGAUUC U CCUGCCUC 1669 GAGGCAGG CUGAUGAGGCCGUUAGGCCGAA IAAUCACU 2168 2416 UGAUUCUC C UGCCUCAG 1670 CUGAGGCA CUGAUGAGGCCGUUAGGCCGAA IAGAAUCA 2169 2417 GAUUCUCC U GCCUCAGC 1671 GCUGAGGC CUGAUGAGGCCGUUAGGCCGAA IGAGAAUC 2170 2420 UCUCCUGC C UCAGCCUC 1672 GAGGCUGA CUGAUGAGGCCGUUAGGCCGAA ICAGGAGA 2171 2421 CUCCUGCC U CAGCCUCC 1673 GGAGGCUG CUGAUGAGGCCGUUAGGCCGAA IGCAGGAG 2172 2423 CCUGCCUC A GCCUCCUG 1674 CAGGAGGC CUGAUGAGGCCGUUAGGCCGAA IAGGCAGG 2173 2426 GCCUCAGC C UCCUGAGU 1675 ACUCAGGA CUGAUGAGGCCGUUAGGCCGAA ICUGAGGC 2174 2427 CCUCAGCC U CCUGAGUA 1676 UACUCAGG CUGAUGAGGCCGUUAGGCCGAA IGCUGAGG 2175 2429 UCAGCCUC C UGAGUAGC 1677 GCUACUCA CUGAUGAGGCCGUUAGGCCGAA IAGGCUGA 2176 2430 CAGCCUCC U GAGUAGCU 1678 AGCUACUC CUGAUGAGGCCGUUAGGCCGAA IGAGGCUG 2177 2438 UGAGUAGC U GGAUUACA 1679 UGUAAUCC CUGAUGAGGCCGUUAGGCCGAA ICUACUCA 2178 2446 UGGAUUAC A GGCAUGUG 1680 CACAUGCC CUGAUGAGGCCGUUAGGCCGAA IUAAUCCA 2179 2450 UUACAGGC A UGUGCCAC 1681 GUGGCACA CUGAUGAGGCCGUUAGGCCGAA ICCUGUAA 2180 2456 GCAUGUGC C ACCCACCC 1682 GGGUGGGU CUGAUGAGGCCGUUAGGCCGAA ICACAUGC 2181 2457 CAUGUGCC A CCCACCCA 1683 UGGGUGGG CUGAUGAGGCCGUUAGGCCGAA IGCACAUG 2182 2459 UGUGCCAC C CACCCAAC 1684 GUUGGGUG CUGAUGAGGCCGUUAGGCCGAA IUGGCACA 2183

2460 GUGCCACC C ACCCAACU 1685 AGUUGGGU CUGAUGAGGCCGUUAGGCCGAA IGUGGCAC 2184 2461 UGCCACCC A CCCAACUA 1686 UAGUUGGG CUGAUGAGGCCGUUAGGCCGAA IGGUGGCA 2185 2463 CCACCCAC C CAACUAAU 1687 AUUAGUUG CUGAUGAGGCCGUUAGGCCGAA IUGGGUGG 2186 2464 CACCCACC C AACUAAUU 1688 AAUUAGUU CUGAUGAGGCCGUUAGGCCGAA IGUGGGUG 2187 2465 ACCCACCC A ACUAAUUU 1689 AAAUUAGU CUGAUGAGGCCGUUAGGCCGAA IGGUGGGU 2188 2468 CACCCAAC U AAUUUUUG 1690 CAAAAAUU CUGAUGAGGCCGUUAGGCCGAA IUUGGGUG 2189 2493 AUAAAGAC A GGGUUUCA 1691 UGAAACCC CUGAUGAGGCCGUUAGGCCGAA IUCUUUAU 2190 2501 AGGGUUUC A CCAUGUUG 1692 CAACAUGG CUGAUGAGGCCGUUAGGCCGAA IAAACCCU 2191 2503 GGUUUCAC C AUGUUGGC 1693 GCCAACAU CUGAUGAGGCCGUUAGGCCGAA IUGAAACC 2192 2504 GUUUCACC A UGUUGGCC 1694 GGCCAACA CUGAUGAGGCCGUUAGGCCGAA IGUGAAAC 2193 2512 AUGUUGGC C AGGCUGGU 1695 ACCAGCCU CUGAUGAGGCCGUUAGGCCGAA ICCAACAU 2194 2513 UGUUGGCC A GGCUGGUC 1696 GACCAGCC CUGAUGAGGCCGUUAGGCCGAA IGCCAACA 2195 2517 GGCCAGGC U GGUCUCAA 1697 UUGAGACC CUGAUGAGGCCGUUAGGCCGAA ICCUGGCC 2196 2522 GGCUGGUC U CAAACUCC 1698 GGAGUUUG CUGAUGAGGCCGUUAGGCCGAA IACCAGCC 2197 2524 CUGGUCUC A AACUCCUG 1699 CAGGAGUU CUGAUGAGGCCGUUAGGCCGAA IAGACCAG 2198 2528 UCUCAAAC U CCUGACCU 1700 AGGUCAGG CUGAUGAGGCCGUUAGGCCGAA IUUUGAGA 2199 2530 UCAAACUC C UGACCUCA 1701 UGAGGUCA CUGAUGAGGCCGUUAGGCCGAA IAGUUUGA 2200 2531 CAAACUCC U GACCUCAA 1702 UUGAGGUC CUGAUGAGGCCGUUAGGCCGAA IGAGUUUG 2201 2535 CUCCUGAC C UCAAGUAA 1703 UUACUUGA CUGAUGAGGCCGUUAGGCCGAA IUCAGGAG 2202 2536 UCCUGACC U CAAGUAAU 1704 AUUACUUG CUGAUGAGGCCGUUAGGCCGAA IGUCAGGA 2203 2538 CUGACCUC A AGUAAUCC 1705 GGAUUACU CUGAUGAGGCCGUUAGGCCGAA IAGGUCAG 2204 2546 AAGUAAUC C ACCUGCCU 1706 AGGCAGGU CUGAUGAGGCCGUUAGGCCGAA IAUUACUU 2205 2547 AGUAAUCC A CCUGCCUC 1707 GAGGCAGG CUGAUGAGGCCGUUAGGCCGAA IGAUUACU 2206 2549 UAAUCCAC C UGCCUCGG 1708 CCGAGGCA CUGAUGAGGCCGUUAGGCCGAA IUGGAUUA 2207 2550 AAUCCACC U GCCUCGGC 1709 GCCGAGGC CUGAUGAGGCCGUUAGGCCGAA IGUGGAUU 2208 2553 CCACCUGC C UCGGCCUC 1710 GAGGCCGA CUGAUGAGGCCGUUAGGCCGAA ICAGGUGG 2209 2554 CACCUGCC U CGGCCUCC 1711 GGAGGCCG CUGAUGAGGCCGUUAGGCCGAA IGCAGGUG 2210 2559 GCCUCGGC C UCCCAAAG 1712 CUUUGGGA CUGAUGAGGCCGUUAGGCCGAA ICCGAGGC 2211 2560 CCUCGGCC U CCCAAAGU 1713 ACUUUGGG CUGAUGAGGCCGUUAGGCCGAA IGCCGAGG 2212 2562 UCGGCCUC C CAAAGUGC 1714 GCACUUUG CUGAUGAGGCCGUUAGGCCGAA IAGGCCGA 2213 2563 CGGCCUCC C AAAGUGCU 1715 AGCACUUU CUGAUGAGGCCGUUAGGCCGAA IGAGGCCG 2214 2564 GGCCUCCC A AAGUGCUG 1716 CAGCACUU CUGAUGAGGCCGUUAGGCCGAA IGGAGGCC 2215 2571 CAAAGUGC U GGGAUUAC 1717 GUAAUCCC CUGAUGAGGCCGUUAGGCCGAA ICACUUUG 2216 2580 GGGAUUAC A GGGAUGAG 1718 CUCAUCCC CUGAUGAGGCCGUUAGGCCGAA IUAAUCCC 2217 2590 GGAUGAGC C ACCGCGCC 1719 GGCGCGGU CUGAUGAGGCCGUUAGGCCGAA ICUCAUCC 2218 2591 GAUGAGCC A CCGCGCCC 1720 GGGCGCGG CUGAUGAGGCCGUUAGGCCGAA IGCUCAUC 2219 2593 UGAGCCAC C GCGCCCAG 1721 CUGGGCGC CUGAUGAGGCCGUUAGGCCGAA IUGGCUCA 2220 2598 CACCGCGC C CAGCCUCA 1722 UGAGGCUG CUGAUGAGGCCGUUAGGCCGAA ICGCGGUG 2221 2599 ACCGCGCC C AGCCUCAU 1723 AUGAGGCU CUGAUGAGGCCGUUAGGCCGAA IGCGCGGU 2222 2600 CCGCGCCC A GCCUCAUC 1724 GAUGAGGC CUGAUGAGGCCGUUAGGCCGAA IGGCGCGG 2223 2603 CGCCCAGC C UCAUCUCU 1725 AGAGAUGA CUGAUGAGGCCGUUAGGCCGAA ICUGGGCG 2224 2604 GCCCAGCC U CAUCUCUU 1726 AAGAGAUG CUGAUGAGGCCGUUAGGCCGAA IGCUGGGC 2225 2606 CCAGCCUC A UCUCUUUG 1727 CAAAGAGA CUGAUGAGGCCGUUAGGCCGAA IAGGCUGG 2226 2609 GCCUCAUC U CUUUGUUC 1728 GAACAAAG CUGAUGAGGCCGUUAGGCCGAA IAUGAGGC 2227 2611 CUCAUCUC U UUGUUCUA 1729 UAGAACAA CUGAUGAGGCCGUUAGGCCGAA IAGAUGAG 2228 2618 CUUUGUUC U AAAGAUGG 1730 CCAUCUUU CUGAUGAGGCCGUUAGGCCGAA IAACAAAG 2229 2633 GGAAAAAC C ACCCCCAA 1731 UUGGGGGU CUGAUGAGGCCGUUAGGCCGAA IUUUUUCC 2230 2634 GAAAAACC A CCCCCAAA 1732 UUUGGGGG CUGAUGAGGCCGUUAGGCCGAA IGUUUUUC 2231 2636 AAAACCAC C CCCAAAUU 1733 AAUUUGGG CUGAUGAGGCCGUUAGGCCGAA IUGGUUUU 2232 2637 AAACCACC C CCAAAUUU 1734 AAAUUUGG CUGAUGAGGCCGUUAGGCCGAA IGUGGUUU 2233 2638 AACCACCC C CAAAUUUU 1735 AAAAUUUG CUGAUGAGGCCGUUAGGCCGAA IGGUGGUU 2234 2639 ACCACCCC C AAAUUUUC 1736 GAAAAUUU CUGAUGAGGCCGUUAGGCCGAA IGGGUGGU 2235 2640 CCACCCCC A AAUUUUCU 1737 AGAAAAUU CUGAUGAGGCCGUUAGGCCGAA IGGGGUGG 2236 2648 AAAUUUUC U UUUUAUAC 1738 GUAUAAAA CUGAUGAGGCCGUUAGGCCGAA IAAAAUUU 2237 2657 UUUUAUAC U AUUAAUGA 1739 UCAUUAAU CUGAUGAGGCCGUUAGGCCGAA IUAUAAAA 2238 2669 AAUGAAUC A AUCAAUUC 1740 GAAUUGAU CUGAUGAGGCCGUUAGGCCGAA IAUUCAUU 2239 2673 AAUCAAUC A AUUCAUAU 1741 AUAUGAAU CUGAUGAGGCCGUUAGGCCGAA IAUUGAUU 2240 2678 AUCAAUUC A UAUCUAUU 1742 AAUAGAUA CUGAUGAGGCCGUUAGGCCGAA IAAUUGAU 2241 2683 UUCAUAUC U AUUUAUUA 1743 UAAUAAAU CUGAUGAGGCCGUUAGGCCGAA IAUAUGAA 2242 2698 UAAAUUUC U ACCGCUUU 1744 AAAGCGGU CUGAUGAGGCCGUUAGGCCGAA IAAAUUUA 2243 2701 AUUUCUAC C GCUUUUAG 1745 CUAAAAGC CUGAUGAGGCCGUUAGGCCGAA IUAGAAAU 2244 2704 UCUACCGC U UUUAGGCC 1746 GGCCUAAA CUGAUGAGGCCGUUAGGCCGAA ICGGUAGA 2245 2712 UUUUAGGC C AAAAAAAU 1747 AUUUUUUU CUGAUGAGGCCGUUAGGCCGAA ICCUAAAA 2246 2713 UUUAGGCC A AAAAAAUG 1748 CAUUUUUU CUGAUGAGGCCGUUAGGCCGAA IGCCUAAA 2247 2733 GAUCGUUC U CUGCCUCA 1749 UGAGGCAG CUGAUGAGGCCGUUAGGCCGAA IAACGAUC 2248 2735 UCGUUCUC U GCCUCACA 1750 UGUGAGGC CUGAUGAGGCCGUUAGGCCGAA IAGAACGA 2249 2738 UUCUCUGC C UCACAUAG 1751 CUAUGUGA CUGAUGAGGCCGUUAGGCCGAA ICAGAGAA 2250 2739 UCUCUGCC U CACAUAGC 1752 GCUAUGUG CUGAUGAGGCCGUUAGGCCGAA IGCAGAGA 2251 2741 UCUGCCUC A CAUAGCUU 1753 AAGCUAUG CUGAUGAGGCCGUUAGGCCGAA IAGGCAGA 2252 2743 UGCCUCAC A UAGCUUAC 1754 GUAAGCUA CUGAUGAGGCCGUUAGGCCGAA IUGAGGCA 2253 2748 CACAUAGC U UACAAGCC 1755 GGCUUGUA CUGAUGAGGCCGUUAGGCCGAA ICUAUGUG 2254 2752 UAGCUUAC A AGCCAGCU 1756 AGCUGGCU CUGAUGAGGCCGUUAGGCCGAA IUAAGCUA 2255 2756 UUACAAGC C AGCUGGAG 1757 CUCCAGCU CUGAUGAGGCCGUUAGGCCGAA ICUUGUAA 2256 2757 UACAAGCC A GCUGGAGA 1758 UCUCCAGC CUGAUGAGGCCGUUAGGCCGAA IGCUUGUA 2257 2760 AAGCCAGC U GGAGAAAU 1759 AUUUCUCC CUGAUGAGGCCGUUAGGCCGAA ICUGGCUU 2258 2776 UAUGGUAC U CAUUAAAA 1760 UUUUAAUG CUGAUGAGGCCGUUAGGCCGAA IUACCAUA 2259 2778 UGGUACUC A UUAAAAAA 1761 UUUUUUAA CUGAUGAGGCCGUUAGGCCGAA IAGUACCA 2260 Input Sequence = NM_002759. Cut Site = CH/. Arm Length = 8. Core Sequence = CUGAUGAG X CGAA (X = GCCGUUAGGC or other stem II) NM_002759 (Homo sapiens protein kinase, interferon-inducible double stranded RNA dependent (PRKR), mRNA.; 2808 bp) Underlined region can be any X sequence or linker, as described herein. "I" stands for Inosine.

[0272] TABLE-US-00010 TABLE X Human PKR Zinzyme and Substrate Sequence Seq Pos Substrate Seq ID Zinzyme ID 10 CGGCGGCG G CGGCGCAG 2261 CUGCGCCG GCCGAAAGGCGAGUGAGGUCU CGCCGCCG 2480 13 CGGCGGCG G CGCAGUUU 2433 AAACUGCG GCCGAAAGGCGAGUGAGGUCU CGCCGCCG 2652 15 GCGGCGGC G CAGUUUGC 2434 GCAAACUG GCCGAAAGGCGAGUGAGGUCU GCCGCCGC 2653 18 GCGGCGCA G UUUGCUCA 2435 UGAGCAAA GCCGAAAGGCGAGUGAGGUCU UGCGCCGC 2654 22 CGCAGUUU G CUCAUACU 2436 AGUAUGAG GCCGAAAGGCGAGUGAGGUCU AAACUGCG 2655 33 CAUACUUU G UGACUUGC 2437 GCAAGUCA GCCGAAAGGCGAGUGAGGUCU AAAGUAUG 2656 40 UGUGACUU G CGGUCACA 2438 UGUGACCG GCCGAAAGGCGAGUGAGGUCU AAGUCACA 2657 43 GACUUGCG G UCACAGUG 2439 CACUGUGA GCCGAAAGGCGAGUGAGGUCU CGCAAGUC 2658 49 CGGUCACA G UGGCAUUC 2440 GAAUGCCA GCCGAAAGGCGAGUGAGGUCU UGUGACCG 2659 52 UCACAGUG G CAUUCAGC 2441 GCUGAAUG GCCGAAAGGCGAGUGAGGUCU CACUGUGA 2660 59 GGCAUUCA G CUCCACAC 2442 GUGUGGAG GCCGAAAGGCGAGUGAGGUCU UGAAUGCC 2661 71 CACACUUG G UAGAACCA 2443 UGGUUCUA GCCGAAAGGCGAGUGAGGUCU CAAGUGUG 2662 83 AACCACAG G CACGACAA 2444 UUGUCGUG GCCGAAAGGCGAGUGAGGUCU CUGUGGUU 2663 92 CACGACAA G CAUAGAAA 2445 UUUCUAUG GCCGAAAGGCGAGUGAGGUCU UUGUCGUG 2664 124 UCAUCGAG G CAUCGAGG 2446 CCUCGAUG GCCGAAAGGCGAGUGAGGUCU CUCGAUGA 2665 132 GCAUCGAG G UCCAUCCC 2447 GGGAUGGA GCCGAAAGGCGAGUGAGGUCU CUCGAUGC 2666 162 AGACCCUG G CUAUCAUA 2448 UAUGAUAG GCCGAAAGGCGAGUGAGGUCU CAGGGUCU 2667 178 AGACCUUA G UCUUCGCU 2449 AGCGAAGA GCCGAAAGGCGAGUGAGGUCU UAAGGUCU 2668 184 UAGUCUUC G CUGGUAUA 2450 UAUACCAG GCCGAAAGGCGAGUGAGGUCU GAAGACUA 2669 188 CUUCGCUG G UAUACUCG 2451 CGAGUAUA GCCGAAAGGCGAGUGAGGUCU CAGCGAAG 2670 196 GUAUACUC G CUGUCUGU 2452 ACAGACAG GCCGAAAGGCGAGUGAGGUCU GAGUAUAC 2671 199 UACUCGCU G UCUGUCAA 2453 UUGACAGA GCCGAAAGGCGAGUGAGGUCU AGCGAGUA 2672 203 CGCUGUCU G UCAACCAG 2454 CUGGUUGA GCCGAAAGGCGAGUGAGGUCU AGACAGCG 2673 211 GUCAACCA G CGGUUGAC 2455 GUCAACCG GCCGAAAGGCGAGUGAGGUCU UGGUUGAC 2674 214 AACCAGCG G UUGACUUU 2456 AAAGUCAA GCCGAAAGGCGAGUGAGGUCU CGCUGGUU 2675 229 UUUUUUAA G CCUUCUUU 2457 AAAGAAGG GCCGAAAGGCGAGUGAGGUCU UUAAAAAA 2676 252 UUUUACCA G UUUCUGGA 2458 UCCAGAAA GCCGAAAGGCGAGUGAGGUCU UGGUAAAA 2677 261 UUUCUGGA G CAAAUUCA 2459 UGAAUUUG GCCGAAAGGCGAGUGAGGUCU UCCAGAAA 2678 270 CAAAUUCA G UUUGCCUU 2460 AAGGCAAA GCCGAAAGGCGAGUGAGGUCU UGAAUUUG 2679 274 UUCAGUUU G CCUUCCUG 2461 CAGGAAGG GCCGAAAGGCGAGUGAGGUCU AAACUGAA 2680 288 CUGGAUUU G UAAAUUGU 2462 ACAAUUUA GCCGAAAGGCGAGUGAGGUCU AAAUCCAG 2681 295 UGUAAAUU G UAAUGACC 2463 GGUCAUUA GCCGAAAGGCGAGUGAGGUCU AAUUUACA 2682 315 AAACUUUA G CAGUUCUU 2464 AAGAACUG GCCGAAAGGCGAGUGAGGUCU UAAAGUUU 2683 318 CUUUAGCA G UUCUUCCA 2465 UGGAAGAA GCCGAAAGGCGAGUGAGGUCU UGCUAAAG 2684 337 UGACUCAG G UUUGCUUC 2466 GAAGCAAA GCCGAAAGGCGAGUGAGGUCU CUGAGUCA 2685 341 UCAGGUUU G CUUCUCUG 2467 CAGAGAAG GCCGAAAGGCGAGUGAGGUCU AAACCUGA 2686 350 CUUCUCUG G CGGUCUUC 2468 GAAGACCG GCCGAAAGGCGAGUGAGGUCU CAGAGAAG 2687 353 CUCUGGCG G UCUUCAGA 2469 UCUGAAGA GCCGAAAGGCGAGUGAGGUCU CGCCAGAG 2688 380 ACACUUCC G UGAUUAUC 2470 GAUAAUCA GCCGAAAGGCGAGUGAGGUCU GGAAGUGU 2689 390 GAUUAUCU G CGUGCAUU 2471 AAUGCACG GCCGAAAGGCGAGUGAGGUCU AGAUAAUC 2690 392 UUAUCUGC G UGCAUUUU 2472 AAAAUGCA GCCGAAAGGCGAGUGAGGUCU GCAGAUAA 2691 394 AUCUGCGU G CAUUUUGG 2473 CCAAAAUG GCCGAAAGGCGAGUGAGGUCU ACGCAGAU 2692 408 UGGACAAA G CUUCCAAC 2474 GUUGGAAG GCCGAAAGGCGAGUGAGGUCU UUUGUCCA 2693 439 AAGAAAUG G CUGGUGAU 2475 AUCACCAG GCCGAAAGGCGAGUGAGGUCU CAUUUCUU 2694 443 AAUGGCUG G UGAUCUUU 2476 AAAGAUCA GCCGAAAGGCGAGUGAGGUCU CAGCCAUU 2695 454 AUCUUUCA G CAGGUUUC 2477 GAAACCUG GCCGAAAGGCGAGUGAGGUCU UGAAAGAU 2696 458 UUCAGCAG G UUUCUUCA 2478 UGAAGAAA GCCGAAAGGCGAGUGAGGUCU CUGCUGAA 2697 488 UACAUACC G UCAGAAGC 2479 GCUUCUGA GCCGAAAGGCGAGUGAGGUCU GGUAUGUA 2698 495 CGUCAGAA G CAGGGAGU 2262 ACUCCCUG GCCGAAAGGCGAGUGAGGUCU UUCUGACG 2481 502 AGCAGGGA G UAGUACUU 2263 AAGUACUA GCCGAAAGGCGAGUGAGGUCU UCCCUGCU 2482 505 AGGGAGUA G UACUUAAA 2264 UUUAAGUA GCCGAAAGGCGAGUGAGGUCU UACUCCCU 2483 525 CAAGAACU G CCUAAUUC 2265 GAAUUAGG GCCGAAAGGCGAGUGAGGUCU AGUUCUUG 2484 555 GAUAGGAG G UUUACAUU 2266 AAUGUAAA GCCGAAAGGCGAGUGAGGUCU CUCCUAUC 2485 568 CAUUUCAA G UUAUAAUA 2267 UAUUAUAA GCCGAAAGGCGAGUGAGGUCU UUGAAAUG 2486 599 UCCAGAAG G UGAAGGUA 2268 UACCUUCA GCCGAAAGGCGAGUGAGGUCU CUUCUGGA 2487 605 AGGUGAAG G UAGAUCAA 2269 UUGAUCUA GCCGAAAGGCGAGUGAGGUCU CUUCACCU 2488 622 AGAAGGAA G CAAAAAAU 2270 AUUUUUUG GCCGAAAGGCGAGUGAGGUCU UUCCUUCU 2489 631 CAAAAAAU G CCGCAGCC 2271 GGCUGCGG GCCGAAAGGCGAGUGAGGUCU AUUUUUUG 2490 634 AAAAUGCC G CAGCCAAA 2272 UUUGGCUG GCCGAAAGGCGAGUGAGGUCU GGCAUUUU 2491 637 AUGCCGCA G CCAAAUUA 2273 UAAUUUGG GCCGAAAGGCGAGUGAGGUCU UGCGGCAU 2492 646 CCAAAUUA G CUGUUGAG 2274 CUCAACAG GCCGAAAGGCGAGUGAGGUCU UAAUUUGG 2493 649 AAUUAGCU G UUGAGAUA 2275 UAUCUCAA GCCGAAAGGCGAGUGAGGUCU AGCUAAUU 2494 676 AAAAGAAG G CAGUUAGU 2276 ACUAACUG GCCGAAAGGCGAGUGAGGUCU CUUCUUUU 2495 679 AGAAGGCA G UUAGUCCU 2277 AGGACUAA GCCGAAAGGCGAGUGAGGUCU UGCCUUCU 2496 683 GGCAGUUA G UCCUUUAU 2278 AUAAAGGA GCCGAAAGGCGAGUGAGGUCU UAACUGCC 2497 743 UUACAUAG G CCUUAUCA 2279 UGAUAAGG GCCGAAAGGCGAGUGAGGUCU CUAUGUAA 2498 760 AUAGAAUU G CCCAGAAG 2280 CUUCUGGG GCCGAAAGGCGAGUGAGGUCU AAUUCUAU 2499 781 GACUAACU G UAAAUUAU 2281 AUAAUUUA GCCGAAAGGCGAGUGAGGUCU AGUUAGUC 2500 795 UAUCAACA G UGUGCAUC 2282 GAUGCACA GCCGAAAGGCGAGUGAGGUCU UGUUCAUA 2501 797 UGAACAGU G UGCAUCGG 2283 CCGAUGCA GCCGAAAGGCGAGUGAGGUCU ACUGUUCA 2502 799 AACAGUGU G CAUCGGGG 2284 CCCCGAUG GCCGAAAGGCGAGUGAGGUCU ACACUGUU 2503 808 CAUCGGGG G UGCAUGGG 2285 CCCAUGCA GCCGAAAGGCGAGUGAGGUCU CCCCGAUG 2504 810 UCGGGGGU G CAUGGGCC 2286 GGCCCAUG GCCGAAAGGCGAGUGAGGUCU ACCCCCGA 2505 816 GUGCAUGG G CCAGAAGG 2287 CCUUCUGG GCCGAAAGGCGAGUGAGGUCU CCAUGCAC 2506 839 UUAUAAAU G CAAAAUGG 2288 CCAUUUUG GCCGAAAGGCGAGUGAGGUCU AUUUAUAA 2507 863 AGAAUAUA G UAUUGGUA 2289 UACCAAUA GCCGAAAGGCGAGUGAGGUCU UAUAUUCU 2508 869 UAGUAUUG G UACAGGUU 2290 AACCUGUA GCCGAAAGGCGAGUGAGGUCU CAAUACUA 2509 875 UGGUACAG G UUCUACUA 2291 UAGUAGAA GCCGAAAGGCGAGUGAGGUCU CUGUACCA 2510 892 AACAGGAA G CAAAACAA 2292 UUGUUUUG GCCGAAAGGCGAGUGAGGUCU UUCCUGUU 2511 904 AACAAUUG G CCGCUAAA 2293 UUUAGCGG GCCGAAAGGCGAGUGAGGUCU CAAUUGUU 2512 907 AAUUGGCC G CUAAACUU 2294 AAGUUUAG GCCGAAAGGCGAGUGAGGUCU GGCCAAUU 2513 916 CUAAACUU G CAUAUCUU 2295 AAGAUAUG GCCGAAAGGCGAGUGAGGUCU AAGUUUAG 2514 949 AAACCUCA G UGAAAUCU 2296 AGAUUUCA GCCGAAAGGCGAGUGAGGUCU UGAGGUUU 2515 966 GACUACCU G UCCUCUGG 2297 CCACAGGA GCCGAAAGGCGAGUGAGGUCU AGGUAGUC 2516 974 GUCCUCUG G UUCUUUUG 2298 CAAAAGAA GCCGAAAGGCGAGUGAGGUCU CAGAGGAC 2517 982 GUUCUUUU G CUACUACG 2299 CGUAGUAG GCCGAAAGGCGAGUGAGGUCU AAAAGAAC 2518 990 GCUACUAC G UGUGAGUC 2300 GACUCACA GCCGAAAGGCGAGUGAGGUCU GUAGUAGC 2519 992 UACUACCU G UGAGUCCC 2301 GGGACUCA GCCGAAAGGCGAGUGAGGUCU ACGUAGUA 2520 996 ACGUCUGA G UCCCAAAG 2302 CUUUGGGA GCCGAAAGGCGAGUGAGGUCU UCACACGU 2521 1004 GUCCCAAA G CAACUCUU 2303 AAGAGUUG GCCGAAAGGCGAGUGAGGUCU UUUGGGAC 2522 1015 ACUCUUUA G UGACCAGC 2304 GCUGGUCA GCCGAAAGGCGAGUGAGGUCU UAAAGAGU 2523 1022 AGUGACCA G CACACUCG 2305 CGAGUGUG GCCGAAAGGCGAGUGAGGUCU UGGUCACU 2524 1030 GCACACUC G CUUCUGAA 2306 UUCAGAAG GCCGAAAGGCGAGUGAGGUCU GAGUGUGC 2525 1052 AUCUGAAG G UGACUUCU 2307 AGAAGUCA GCCGAAAGGCGAGUGAGGUCU CUUCAGAU 2526 1063 ACUUCUGA G CAGAUACA 2308 UGUAUCUG GCCGAAAGGCGAGUGAGGUCU UGAGAAGU 2527 1091 UUCUAACA G UGACAGUU 2309 AACUGUCA GCCGAAAGGCGAGUGAGGUCU UGUUAGAA 2528 1097 CAGUGACA G UUUAAACA 2310 UGUUUAAA GCCGAAAGGCGAGUGAGGUCU UGUCACUG 2529 1106 UUUAAACA G UUCUUCGU 2311 ACGAAGAA GCCGAAAGGCGAGUGAGGUCU UGUUUAAA 2530 1113 AGUUCUUC G UUGCUUAU 2312 AUAAGCAA GCCGAAAGGCGAGUGAGGUCU GAAGAACU 2531 1116 UCUUCGUU G CUUAUGAA 2313 UUCAUAAG GCCGAAAGGCGAGUGAGGUCU AACGAAGA 2532 1127 UAUGAAUG G UCUCAGAA 2314 UUCUGAGA GCCGAAAGGCGAGUGAGGUCU CAUUCAUA 2533 1150 AAAGGAAG G CAAAAAGA 2315 UCUUUUUG GCCGAAAGGCGAGUGAGGUCU CUUCCUUU 2534 1165 GAUCUUUG G CACCCAGA 2316 UCUGGGUG GCCGAAAGGCGAGUGAGGUCU CAAAGAUC 2535 1203 GAAACAAA G UAUACUGU 2317 ACAGUAUA GCCGAAAGGCGAGUGAGGUCU UUUGUUUC 2536 1210 AGUAUACU G UGGACAAG 2318 CUUGUCCA GCCGAAAGGCGAGUGAGGUCU AGUAUACU 2537 1221 GACAAGAG G UUUGGCAU 2319 AUGCCAAA GCCGAAAGGCGAGUGAGGUCU CUCUUGUC 2538 1226 GAGGUUUG G CAUGGAUU 2320 AAUCCAUG GCCGAAAGGCGAGUGAGGUCU CAAACCUC 2539 1256 AUUAAUUG G CUCAGGUG 2321 CACCUGAG GCCGAAAGGCGAGUGAGGUCU CAAUUAAU 2540 1262 UGGCUCAG G UGGAUUUG 2322 CAAAUCCA GCCGAAAGGCGAGUGAGGUCU CUGAGCCA 2541 1271 UGGAUUUG G CCAAGUUU 2323 AAACUUGG GCCGAAAGGCGAGUGAGGUCU CAAAUCCA 2542 1276 UUGGCCAA G UUUUCAAA 2324 UUUGAAAA GCCGAAAGGCGAGUGAGGUCU UUGGCCAA 2543

1285 UUUUCAAA G CAAAACAC 2325 GUGUUUUG GCCGAAAGGCGAGUGAGGUCU UUUGAAAA 2544 1315 AGACUUAC G UUAUUAAA 2326 UUUAAUAA GCCGAAAGGCGAGUGAGGUCU GUAAGUCU 2545 1325 UAUUAAAC G UGUUAAAU 2327 AUUUAACA GCCGAAAGGCGAGUGAGGUCU GUUUAAUA 2546 1327 UUAAACGU G UUAAAUAU 2328 AUAUUUAA GCCGAAAGGCGAGUGAGGUCU ACGUUUAA 2547 1348 ACGAGAAG G CGGAGCGU 2329 ACGCUCCG GCCGAAAGGCGAGUGAGGUCU CUUCUCGU 2548 1353 AAGGCGGA G CGUGAAGU 2330 ACUUCACG GCCGAAAGGCGAGUGAGGUCU UCCGCCUU 2549 1355 GGCGGAGC G UGAAGUAA 2331 UUACUUCA GCCGAAAGGCGAGUGAGGUCU GCUCCGCC 2550 1360 AGCGUGAA G UAAAAGCA 2332 UGCUUUUA GCCGAAAGGCGAGUGAGGUCU UUCACGCU 2551 1366 AAGUAAAA G CAUUGGCA 2333 UGCCAAUG GCCGAAAGGCGAGUGAGGUCU UUUUACUU 2552 1372 AAGCAUUG G CAAAACUU 2334 AAGUUUUG GCCGAAAGGCGAGUGAGGUCU CAAUGCUU 2553 1387 UUGAUCAU G UAAAUAUU 2335 AAUAUUUA GCCGAAAGGCGAGUGAGGUCU AUGAUCAA 2554 1396 UAAAUAUU G UUCACUAC 2336 GUAGUGAA GCCGAAAGGCGAGUGAGGUCU AAUAUUUA 2555 1409 CUACAAUG G CUGUUGGG 2337 CCCAACAG GCCGAAAGGCGAGUGAGGUCU CAUUGUAG 2556 1412 CAAUGGCU G UUGGGAUG 2338 CAUCCCAA GCCGAAAGGCGAGUGAGGUCU AGCCAUUG 2557 1445 UGAGACCA G UGAUGAUU 2339 AAUCAUCA GCCGAAAGGCGAGUGAGGUCU UGGUCUCA 2558 1463 UCUUGAGA G CAGUGAUU 2340 AAUCACUG GCCGAAAGGCGAGUGAGGUCU UCUCAAGA 2559 1466 UGAGAGCA G UGAUUAUG 2341 CAUAAUCA GCCGAAAGGCGAGUGAGGUCU UGCUCUCA 2560 1487 UGAGAACA G CAAAAAUA 2342 UAUUUUUG GCCGAAAGGCGAGUGAGGUCU UGUUCUCA 2561 1496 CAAAAAUA G UUCAAGGU 2343 ACCUUGAA GCCGAAAGGCGAGUGAGGUCU UAUUUUUG 2562 1503 AGUUCAAG G UCAAAGAC 2344 GUCUUUGA GCCGAAAGGCGAGUGAGGUCU CUUGAACU 2563 1515 AAGACUAA G UGCCUUUU 2345 AAAAGGCA GCCGAAAGGCGAGUGAGGUCU UUAGUCUU 2564 1517 GACUAAGU G CCUUUUCA 2346 UGAAAAGG GCCGAAAGGCGAGUGAGGUCU ACUUAGUC 2565 1541 GGAAUUCU G UGAUAAAG 2347 CUUUAUCA GCCGAAAGGCGAGUGAGGUCU AGAAUUCC 2566 1583 AAGAAGAG G CGAGAAAC 2348 GUUUCUCG GCCGAAAGGCGAGUGAGGUCU CUCUUCUU 2567 1600 UAGACAAA G UUUUGGCU 2349 AGCCAAAA GCCGAAAGGCGAGUGAGGUCU UUUGUCUA 2568 1606 AAGUUUUG G CUUUGGAA 2350 UUCCAAAG GCCGAAAGGCGAGUGAGGUCU CAAAACUU 2569 1639 CAAAAGGG G UGGAUUAU 2351 AUAAUCCA GCCGAAAGGCGAGUGAGGUCU CCCUUUUG 2570 1683 GAUCUUAA G CCAAGUAA 2352 UUACUUGG GCCGAAAGGCGAGUGAGGUCU UUAAGAUC 2571 1688 UAAGCCAA G UAAUAUAU 2353 AUAUAUUA GCCGAAAGGCGAGUGAGGUCU UUGGCUUA 2572 1702 UAUUCUUA G UAGAUACA 2354 UGUAUCUA GCCGAAAGGCGAGUGAGGUCU UAAGAAUA 2573 1717 CAAAACAA G UAAAGAUU 2355 AAUCUUUA GCCGAAAGGCGAGUGAGGUCU UUGUUUUG 2574 1741 UUGGACUU G UAACAUCU 2356 AGAUGUUA GCCGAAAGGCGAGUGAGGUCU AAGUCCAA 2575 1767 GAUGGAAA G CGAACAAG 2357 CUUGUUCG GCCGAAAGGCGAGUGAGGUCU UUUCCAUC 2576 1778 AACAAGGA G UAAGGGAA 2358 UUCCCUUA GCCGAAAGGCGAGUGAGGUCU UCCUUGUU 2577 1791 GGAACUUU G CGAUACAU 2359 AUGUAUCG GCCGAAAGGCGAGUGAGGUCU AAAGUUCC 2578 1802 AUACAUGA G CCCAGAAC 2360 GUUCUGGG GCCGAAAGGCGAGUGAGGUCU UCAUGUAU 2579 1821 AUUUCUUC G CAAGACUA 2361 UAGUCUUG GCCGAAAGGCGAGUGAGGUCU GAAGAAAU 2580 1840 GAAAGGAA G UGGACCUC 2362 GAGGUCCA GCCGAAAGGCGAGUGAGGUCU UUCCUUUC 2581 1852 ACCUCUAC G CUUUGGGG 2363 CCCCAAAG GCCGAAAGGCGAGUGAGGUCU GUAGAGGU 2582 1860 GCUUUGGG G CUAAUUCU 2364 AGAAUUAG GCCGAAAGGCGAGUGAGGUCU CCCAAAGC 2583 1870 UAAUUCUU G CUGAACUU 2365 AAGUUCAG GCCGAAAGGCGAGUGAGGUCU AAGAAUUA 2584 1885 UUCUUCAU G UAUGUGAC 2366 GUCACAUA GCCGAAAGGCGAGUGAGGUCU AUGAAGAA 2585 1889 UCAUGUAU G UGACACUG 2367 CAGUGUCA GCCGAAAGGCGAGUGAGGUCU AUACAUGA 2586 1897 GUGACACU G CUUUUGAA 2368 UUCAAAAG GCCGAAAGGCGAGUGAGGUCU AGUGUCAC 2587 1914 ACAUCAAA G UUUUUCAC 2369 GUGAAAAA GCCGAAAGGCGAGUGAGGUCU UUUGAUGU 2588 1937 ACGGGAUG G CAUCAUCU 2370 AGAUGAUG GCCGAAAGGCGAGUGAGGUCU CAUCCCGU 2589 2047 CCUUGACU G UGUGGAAG 2371 CUUCCACA GCCGAAAGGCGAGUGAGGUCU AGUCAAGG 2590 2049 UUGACUGU G UGGAAGAA 2372 UUCUUCCA GCCGAAAGGCGAGUGAGGUCU ACAGUCAA 2591 2060 GAAGAAAA G CCCAGAGA 2373 UCUCUGGG GCCGAAAGGCGAGUGAGGUCU UUUUCUUC 2592 2087 ACACACAU G UUAGAGCC 2374 GGCUCUAA GCCGAAAGGCGAGUGAGGUCU AUGUGUGU 2593 2093 AUGUUAGA G CCCUUCUG 2375 CAGAAGGG GCCGAAAGGCGAGUGAGGUCU UCUAACAU 2594 2107 CUGAAAAA G UAUCCUGC 2376 GCAGGAUA GCCGAAAGGCGAGUGAGGUCU UUUUUCAG 2595 2114 AGUAUCCU G CUUCUGAU 2377 AUCAGAAG GCCGAAAGGCGAGUGAGGUCU AGGAUACU 2596 2125 UCUGAUAU G CAGUUUUC 2378 GAAAACUG GCCGAAAGGCGAGUGAGGUCU AUAUCAGA 2597 2128 GAUAUGCA G UUUUCCUU 2379 AAGGAAAA GCCGAAAGGCGAGUGAGGUCU UGCAUAUC 2598 2153 UAAAAUCU G CUAGGGAA 2380 UUCCCUAG GCCGAAAGGCGAGUGAGGUCU AGAUUUUA 2599 2192 AUUUUAAU G UUUCCUUU 2381 AAAGGAAA GCCGAAAGGCGAGUGAGGUCU AUUAAAAU 2600 2230 AUCUUUCU G CAGAAACA 2382 UGUUUCUG GCCGAAAGGCGAGUGAGGUCU AGAAAGAU 2601 2244 ACAGAAAG G UUUUCUUC 2383 GAAGAAAA GCCGAAAGGCGAGUGAGGUCU CUUUCUGU 2602 2258 UUCUUUUU G CUUCAAAA 2384 UUUUGAAG GCCGAAAGGCGAGUGAGGUCU AAAAAGAA 2603 2293 UUUUCCUG G CUCAUCUC 2385 GAGAUGAG GCCGAAAGGCGAGUGAGGUCU CAGGAAAA 2604 2332 AAGACAGA G UCUCGCUC 2386 GAGCGAGA GCCGAAAGGCGAGUGAGGUCU UCUGUCUU 2605 2337 AGAGUCUC G CUCUGUUG 2387 CAACAGAG GCCGAAAGGCGAGUGAGGUCU GAGACUCU 2606 2342 CUCGCUCU G UUGCCCAG 2388 CUGGGCAA GCCGAAAGGCGAGUGAGGUCU AGAGCGAG 2607 2345 GCUCUGUU G CCCAGGCU 2389 AGCCUGGG GCCGAAAGGCGAGUGAGGUCU AACAGAGC 2608 2351 UUGCCCAG G CUGGAGUG 2390 CACUCCAG GCCGAAAGGCGAGUGAGGUCU CUGGGCAA 2609 2357 AGGCUGGA G UGCAAUGA 2391 UCAUUGCA GCCGAAAGGCGAGUGAGGUCU UCCAGCCU 2610 2359 GCUGGAGU G CAAUGACA 2392 UGUCAUUG GCCGAAAGGCGAGUGAGGUCU ACUCCAGC 2611 2370 AUGACACA G UCUUGGCU 2393 AGCCAAGA GCCGAAAGGCGAGUGAGGUCU UGUGUCAU 2612 2376 CAGUCUUG G CUCACUGC 2394 GCAGUGAG GCCGAAAGGCGAGUGAGGUCU CAAGACUG 2613 2383 GGCUCACU G CAACUUCU 2395 AGAAGUUG GCCGAAAGGCGAGUGAGGUCU AGUGAGCC 2614 2392 CAACUUCU G CCUCUUGG 2396 CCAAGAGG GCCGAAAGGCGAGUGAGGUCU AGAAGUUG 2615 2401 CCUCUUGG G UUCAAGUG 2397 CACUUGAA GCCGAAAGGCGAGUGAGGUCU CCAAGAGG 2616 2407 GGGUUCAA G UGAUUCUC 2398 GAGAAUCA GCCGAAAGGCGAGUGAGGUCU UUGAACCC 2617 2418 AUUCUCCU G CCUCAGCC 2399 GGCUGAGG GCCGAAAGGCGAGUGAGGUCU AGGAGAAU 2618 2424 CUGCCUCA G CCUCCUGA 2400 UCAGGAGG GCCGAAAGGCGAGUGAGGUCU UGAGGCAG 2619 2433 CCUCCUGA G UAGCUGGA 2401 UCCAGCUA GCCGAAAGGCGAGUGAGGUCU UCAGGAGG 2620 2436 CCUGAGUA G CUGGAUUA 2402 UAAUCCAG GCCGAAAGGCGAGUGAGGUCU UACUCAGG 2621 2448 GAUUACAG G CAUGUGCC 2403 GGCACAUG GCCGAAAGGCGAGUGAGGUCU CUGUAAUC 2622 2452 ACAGGCAU G UGCCACCC 2404 GGGUGGCA GCCGAAAGGCGAGUGAGGUCU AUGCCUGU 2623 2454 AGGCAUGU G CCACCCAC 2405 GUGGGUGG GCCGAAAGGCGAGUGAGGUCU ACAUGCCU 2624 2476 UAAUUUUU G UGUUUUUA 2406 UAAAAACA GCCGAAAGGCGAGUGAGGUCU AAAAAUUA 2625 2478 AUUUUUGU G UUUUUAAU 2407 AUUAAAAA GCCGAAAGGCGAGUGAGGUCU ACAAAAAU 2626 2496 AAGACAGG G UUUCACCA 2408 UGGUGAAA GCCGAAAGGCGAGUGAGGUCU CCUGUCUU 2627

2506 UUCACCAU G UUGGCCAG 2409 CUGGCCAA GCCGAAAGGCGAGUGAGGUCU AUGGUGAA 2628 2510 CCAUGUUG G CCAGGCUG 2410 CAGCCUGG GCCGAAAGGCGAGUGAGGUCU CAACAUGG 2629 2515 UUGGCCAG G CUGGUCUC 2411 GAGACCAG GCCGAAAGGCGAGUGAGGUCU CUGGCCAA 2630 2519 CCAGGCUG G UCUCAAAC 2412 GUUUGAGA GCCGAAAGGCGAGUGAGGUCU CAGCCUGG 2631 2540 GACCUCAA G UAAUCCAC 2413 GUGGAUUA GCCGAAAGGCGAGUGAGGUCU UUGAGGUC 2632 2551 AUCCACCU G CCUCGGCC 2414 GGCCGAGG GCCGAAAGGCGAGUGAGGUCU AGGUGGAU 2633 2557 CUGCCUCG G CCUCCCAA 2415 UUGGGAGG GCCGAAAGGCGAGUGAGGUCU CGAGGCAG 2634 2567 CUCCCAAA G UGCUGGGA 2416 UCCCAGCA GCCGAAAGGCGAGUGAGGUCU UUUGGGAG 2635 2569 CCCAAAGU G CUGGGAUU 2417 AAUCCCAG GCCGAAAGGCGAGUGAGGUCU ACUUUGGG 2636 2588 AGGGAUGA G CCACCGCG 2418 CGCGGUGG GCCGAAAGGCGAGUGAGGUCU UCAUCCCU 2637 2594 GAGCCACC G CGCCCAGC 2419 GCUGGGCG GCCGAAAGGCGAGUGAGGUCU GGUGGCUC 2638 2596 GCCACCGC G CCCAGCCU 2420 AGGCUGGG GCCGAAAGGCGAGUGAGGUCU GCGGUGGC 2639 2601 CGCGCCCA G CCUCAUCU 2421 AGAUGAGG GCCGAAAGGCGAGUGAGGUCU UGGGCGCG 2640 2614 AUCUCUUU G UUCUAAAG 2422 CUUUAGAA GCCGAAAGGCGAGUGAGGUCU AAAGAGAU 2641 2702 UUUCUACC G CUUUUAGG 2423 CCUAAAAG GCCGAAAGGCGAGUGAGGUCU GGUAGAAA 2642 2710 GCUUUUAG G CCAAAAAA 2424 UUUUUUGG GCCGAAAGGCGAGUGAGGUCU CUAAAAGC 2643 2721 AAAAAAAU G UAAGAUCG 2425 CGAUCUUA GCCGAAAGGCGAGUGAGGUCU AUUUUUUU 2644 2729 GUAAGAUC G UUCUCUGC 2426 GCAGAGAA GCCGAAAGGCGAGUGAGGUCU GAUCUUAC 2645 2736 CGUUCUCU G CCUCACAU 2427 AUGUGAGG GCCGAAAGGCGAGUGAGGUCU AGAGAACG 2646 2746 CUCACAUA G CUUACAAG 2428 CUUGUAAG GCCGAAAGGCGAGUGAGGUCU UAUGUGAG 2647 2754 GCUUACAA G CCAGCUGG 2429 CCAGCUGG GCCGAAAGCCCAGUGAGGUCU UUGUAAGC 2648 2758 ACAAGCCA G CUGGAGAA 2430 UUCUCCAG GCCGAAACGCGAGUGAGCUCU UCGCUUGU 2649 2772 GAAAUAUG G UACUCAUU 2431 AAUGAGUA GCCGAAAGGCGAGUGAGGUCU CAUAUUUC 2650 2796 AAAAAAAA G UGAUGUAC 2432 GUACAUCA GCCGAAAGGCGAGUGAGGUCU UUUUUUUU 2651 Input Sequence = NM_002759. Cut Site = G/Y Arm Length = 8. Core Sequence = GCcgaaagGCGaGuCaaGGuCu NM_002759 (Homo sapiens protein kinase, interferon-inducible double stranded RNA dependent (PRKR), mRNA.; 2808 bp)

[0273] TABLE-US-00011 TABLE XI Human PKR DNAzyme and Substrate Sequence Seq Pos Substrate Seq ID DNAzyme ID 10 CGGCGGCG G CGGCGCAG 2261 CTGCGCCG GGCTAGCTACAACGA CGCCGCCG 2904 13 CGGCGGCG G CGCAGUUU 2433 AAACTGCG GGCTAGCTACAACGA CGCCGCCG 2905 15 GCGGCGGC G CAGUUUGC 2434 GCAAACTG GGCTAGCTACAACGA GCCGCCGC 2906 18 GCGGCGCA G UUUGCUCA 2435 TGAGCAAA GGCTAGCTACAACGA TGCGCCGC 2907 22 CGCAGUUU G CUCAUACU 2436 AGTATGAG GGCTAGCTACAACGA AAACTGCG 2908 26 GUUUGCUC A UACUUUGU 1265 ACAAAGTA GGCTAGCTACAACGA GAGCAAAC 2909 28 UUGCUCAU A CUUUGUGA 4 TCACAAAG GGCTAGCTACAACGA ATGAGCAA 2910 33 CAUACUUU G UGACUUGC 2437 GCAAGTCA GGCTAGCTACAACGA AAAGTATG 2911 36 ACUUUGUG A CUUGCGGU 2699 ACCGCAAG GGCTAGCTACAACGA CACAAAGT 2912 40 UGUGACUU G CGGUCACA 2438 TGTGACCG GGCTAGCTACAACGA AAGTCACA 2913 43 GACUUGCG G UCACAGUG 2439 CACTGTGA GGCTAGCTACAACGA CGCAAGTC 2914 46 UUGCGGUC A CAGUGGCA 1268 TGCCACTG GGCTAGCTACAACGA GACCGCAA 2915 49 CGGUCACA G UGGCAUUC 2440 GAATGCCA GGCTAGCTACAACGA TGTGACCG 2916 52 UCACAGUG G CAUUCAGC 2441 GCTGAATG GGCTAGCTACAACGA CACTGTGA 2917 54 ACAGUGGC A UUCAGCUC 1270 GAGCTGAA GGCTAGCTACAACGA GCCACTGT 2918 59 GGCAUUCA G CUCCACAC 2442 GTGTGGAG GGCTAGCTACAACGA TGAATGCC 2919 64 UCAGCUCC A CACUUGGU 1274 ACCAAGTG GGCTAGCTACAACGA GGAGCTGA 2920 66 AGCUCCAC A CUUGGUAG 1275 CTACCAAG GGCTAGCTACAACGA GTGGAGCT 2921 71 CACACUUG G UAGAACCA 2443 TGGTTCTA GGCTAGCTACAACGA CAAGTGTG 2922 76 UUGGUAGA A CCACAGGC 2700 GCCTGTGG GGCTAGCTACAACGA TCTACCAA 2923 79 GUAGAACC A CAGGCACG 1278 CGTGCCTG GGCTAGCTACAACGA GGTTCTAC 2924 83 AACCACAG G CACGACAA 2444 TTGTCGTG GGCTAGCTACAACGA CTGTGGTT 2925 85 CCACAGGC A CGACAAGC 1280 GCTTGTCG GGCTAGCTACAACGA GCCTGTGG 2926 88 CAGGCACG A CAAGCAUA 2701 TATGCTTG GGCTAGCTACAACGA CGTGCCTG 2927 92 CACGACAA G CAUAGAAA 2445 TTTCTATG GGCTAGCTACAACGA TTGTCGTG 2928 94 CGACAAGC A UAGAAACA 1282 TGTTTCTA GGCTAGCTACAACGA GCTTGTCG 2929 100 GCAUAGAA A CAUCCUAA 2702 TTAGGATG GGCTAGCTACAACGA TTCTATGC 2930 102 AUAGAAAC A UCCUAAAC 1283 GTTTAGGA GGCTAGCTACAACGA GTTTCTAT 2931 109 CAUCCUAA A CAAUCUUC 2703 GAAGATTG GGCTAGCTACAACGA TTAGGATG 2932 112 CCUAAACA A UCUUCAUC 2704 GATGAAGA GGCTAGCTACAACGA TGTTTAGG 2933 118 CAAUCUUC A UCGAGGCA 1288 TGCCTCGA GGCTAGCTACAACGA GAAGATTG 2934 124 UCAUCGAG C CAUCGAGG 2446 CCTCGATG GGCTAGCTACAACGA CTCGATGA 2935 126 AUCGAGGC A UCCAGGUC 1289 GACCTCGA GGCTAGCTACAACGA GCCTCGAT 2936 132 GCAUCGAG G UCCAUCCC 2447 GGGATGGA GGCTAGCTACAACGA CTCGATGC 2937 136 CGAGGUCC A UCCCAAUA 1291 TATTGGGA GGCTAGCTACAACGA GGACCTCG 2938 142 CCAUCCCA A UAAAAAUC 2705 GATTTTTA GGCTAGCTACAACGA TGGGATGG 2939 148 CAAUAAAA A UCAGGAGA 2706 TCTCCTGA GGCTAGCTACAACGA TTTTATTG 2940 156 AUCAGGAG A CCCUGGCU 2707 AGCCAGGG GGCTAGCTACAACGA CTCCTGAT 2941 162 AGACCCUG G CUAUCAUA 2448 TATGATAG GGCTAGCTACAACGA CAGGGTCT 2942 165 CCCUGGCU A UCAUAGAC 26 GTCTATGA GGCTAGCTACAACGA AGCCAGGG 2943 168 UGGCUAUC A UAGACCUU 1300 AAGGTCTA GGCTAGCTACAACGA GATAGCCA 2944 172 UAUCAUAG A CCUUAGUC 2708 GACTAAGG GGCTAGCTACAACGA CTATGATA 2945 178 AGACCUUA G UCUUCGCU 2449 AGCGAAGA GGCTAGCTACAACGA TAAGGTCT 2946 184 UAGUCUUC G CUGGUAUA 2450 TATACCAG GGCTAGCTACAACGA GAAGACTA 2947 188 CUUCGCUG G UAUACUCG 2451 CGAGTATA GGCTAGCTACAACGA CAGCGAAG 2948 190 UCGCUGGU A UACUCGCU 34 AGCGAGTA GGCTAGCTACAACGA ACCAGCGA 2949 192 GCUGGUAU A CUCGCUGU 35 ACAGCGAG GGCTAGCTACAACGA ATACCAGC 2950 196 GUAUACUC G CUGUCUGU 2452 ACAGACAG GGCTAGCTACAACGA GAGTATAC 2951 199 UACUCGCU G UCUGUCAA 2453 TTGACAGA GGCTAGCTACAACGA AGCGAGTA 2952 203 CGCUGUCU G UCAACCAG 2454 CTGGTTGA GGCTAGCTACAACGA AGACAGCG 2953 207 GUCUGUCA A CCAGCGGU 2709 ACCGCTGG GGCTAGCTACAACGA TGACAGAC 2954 211 GUCAACCA G CGGUUGAC 2455 GTCAACCG GGCTAGCTACAACGA TGGTTGAC 2955 214 AACCAGCG G UUGACUUU 2456 AAAGTCAA GGCTAGCTACAACGA CGCTGGTT 2956 218 AGCGGUUG A CUUUUUUU 2710 AAAAAAAG GGCTAGCTACAACGA CAACCGCT 2957 229 UUUUUUAA G CCUUCUUU 2457 AAAGAAGG GGCTAGCTACAACGA TTAAAAAA 2958 248 UCUCUUUU A CCAGUUUC 59 GAAACTGG GGCTAGCTACAACGA AAAAGAGA 2959 252 UUUUACCA G UUUCUGGA 2458 TCCAGAAA GGCTAGCTACAACGA TGGTAAAA 2960 261 UUUCUGGA G CAAAUUCA 2459 TGAATTTG GGCTAGCTACAACGA TCCAGAAA 2961 265 UGGAGCAA A UUCAGUUU 2711 AAACTGAA GGCTAGCTACAACGA TTGCTCCA 2962 270 CAAAUUCA G UUUGCCUU 2460 AAGGCAAA GGCTAGCTACAACGA TGAATTTG 2963 274 UUCAGUUU G CCUUCCUG 2461 CAGGAAGG GGCTAGCTACAACGA AAACTGAA 2964 284 CUUCCUGG A UUUGUAAA 2712 TTTACAAA GGCTAGCTACAACGA CCAGGAAG 2965 288 CUGGAUUU G UAAAUUGU 2462 ACAATTTA GGCTAGCTACAACGA AAATCCAG 2966 292 AUUUGUAA A UUGUAAUG 2713 CATTACAA GGCTAGCTACAACGA TTACAAAT 2967 295 UGUAAAUU G UAAUGACC 2463 GGTCATTA GGCTAGCTACAACGA AATTTACA 2968 298 AAAUUGUA A UGACCUCA 2714 TGAGGTCA GGCTAGCTACAACGA TACAATTT 2969 301 UUGUAAUG A CCUCAAAA 2715 TTTTGAGG GGCTAGCTACAACGA CATTACAA 2970 309 ACCUCAAA A CUUUAGCA 2716 TGCTAAAG GGCTAGCTACAACGA TTTGAGGT 2971 315 AAACUUUA G CAGUUCUU 2464 AAGAACTG GGCTAGCTACAACGA TAAAGTTT 2972 318 CUUUAGCA G UUCUUCCA 2465 TGGAAGAA GGCTAGCTACAACGA TGCTAAAG 2973 326 GUUCUUCC A UCUGACUC 1333 GAGTCAGA GGCTAGCTACAACGA GGAAGAAC 2974 331 UCCAUCUG A CUCAGGUU 2717 AACCTGAG GGCTAGCTACAACGA CAGATGGA 2975 337 UGACUCAG G UUUGCUUC 2466 GAAGCAAA GGCTAGCTACAACGA CTGAGTCA 2976 341 UCAGGUUU G CUUCUCUG 2467 CAGAGAAG GGCTAGCTACAACGA AAACCTGA 2977 350 CUUCUCUG G CGGUCUUC 2468 GAAGACCG GGCTAGCTACAACGA CAGAGAAG 2978 353 CUCUGGCG G UCUUCAGA 2469 TCTGAAGA GGCTAGCTACAACGA CGCCAGAG 2979 362 UCUUCAGA A UCAACAUC 2718 GATGTTGA GGCTAGCTACAACGA TCTGAAGA 2980 366 CAGAAUCA A CAUCCACA 2719 TGTGGATG GGCTAGCTACAACGA TGATTCTG 2981 368 GAAUCAAC A UCCACACU 1343 AGTGTGGA GGCTAGCTACAACGA GTTGATTC 2982 372 CAACAUCC A CACUUCCG 1345 CGGAAGTG GGCTAGCTACAACGA GGATGTTG 2983 374 ACAUCCAC A CUUCCGUG 1346 CACGGAAG GGCTAGCTACAACGA GTGGATGT 2984 380 ACACUUCC G UGAUUAUC 2470 GATAATCA GGCTAGCTACAACGA GGAAGTGT 2985 383 CUUCCGUG A UUAUCUGC 2720 GCAGATAA GGCTAGCTACAACGA CACGGAAG 2986 386 CCGUGAUU A UCUGCGUG 97 CACGCAGA GGCTAGCTACAACGA AATCACGG 2987 390 GAUUAUCU G CGUGCAUU 2471 AATGCACG GGCTAGCTACAACGA AGATAATC 2988 392 UUAUCUGC G UGCAUUUU 2472 AAAATGCA GGCTAGCTACAACGA GCAGATAA 2989 394 AUCUGCGU G CAUUUUGG 2473 CCAAAATG GGCTAGCTACAACGA ACGCAGAT 2990 396 CUGCGUGC A UUUUGGAC 1350 GTCCAAAA GGCTAGCTACAACGA GCACGCAG 2991 403 CAUUUUGG A CAAAGCUU 2721 AAGCTTTG GGCTAGCTACAACGA CCAAAATG 2992 408 UGGACAAA G CUUCCAAC 2474 GTTGGAAG GGCTAGCTACAACGA TTTGTCCA 2993 415 AGCUUCCA A CCAGGAUA 2722 TATCCTGG GGCTAGCTACAACGA TGGAAGCT 2994 421 CAACCAGG A UACGGGAA 2723 TTCCCGTA GGCTAGCTACAACGA CCTGGTTG 2995 423 ACCAGGAU A CGGGAAGA 104 TCTTCCCG GGCTAGCTACAACGA ATCCTGGT 2996 436 AAGAAGAA A UGGCUGGU 2724 ACCAGCCA GGCTAGCTACAACGA TTCTTCTT 2997 439 AAGAAAUG G CUGGUGAU 2475 ATCACCAG GGCTAGCTACAACGA CATTTCTT 2998 443 AAUGGCUG G UGAUCUUU 2476 AAAGATCA GGCTAGCTACAACGA CAGCCATT 2999 446 GGCUGGUG A UCUUUCAG 2725 CTGAAAGA GGCTAGCTACAACGA CACCAGCC 3000 454 AUCUUUCA G CAGGUUUC 2477 GAAACCTG GGCTAGCTACAACGA TGAAAGAT 3001 458 UUCAGCAG G UUUCUUCA 2478 TGAAGAAA GGCTAGCTACAACGA CTGCTGAA 3002 466 GUUUCUUC A UGGAGGAA 1362 TTCCTCCA GGCTAGCTACAACGA GAAGAAAC 3003 474 AUGGAGGA A CUUAAUAC 2726 GTATTAAG GGCTAGCTACAACGA TCCTCCAT 3004 479 GGAACUUA A UACAUACC 2727 GGTATGTA GGCTAGCTACAACGA TAAGTTCC 3005 481 AACUUAAU A CAUACCGU 116 ACGGTATG GGCTAGCTACAACGA ATTAAGTT 3006 483 CUUAAUAC A UACCGUCA 1364 TGACGGTA GGCTAGCTACAACGA GTATTAAG 3007 485 UAAUACAU A CCGUCAGA 117 TCTGACGG GGCTAGCTACAACGA ATGTATTA 3008 488 UACAUACC G UCAGAAGC 2479 GCTTCTGA GGCTAGCTACAACGA GGTATGTA 3009 495 CGUCAGAA G CAGGGAGU 2262 ACTCCCTG GGCTAGCTACAACGA TTCTGACG 3010 502 AGCAGGGA G UAGUACUU 2263 AAGTACTA GGCTAGCTACAACGA TCCCTGCT 3011 505 AGGGAGUA G UACUUAAA 2264 TTTAAGTA GGCTAGCTACAACGA TACTCCCT 3012 507 GGAGUAGU A CUUAAAUA 120 TATTTAAG GGCTAGCTACAACGA ACTACTCC 3013 513 GUACUUAA A UAUCAAGA 2728 TCTTGATA GGCTAGCTACAACGA TTAAGTAC 3014 515 ACUUAAAU A UCAAGAAC 123 GTTCTTGA GGCTAGCTACAACGA ATTTAAGT 3015 522 UAUCAAGA A CUGCCUAA 2729 TTAGGCAG GGCTAGCTACAACGA TCTTGATA 3016 525 CAAGAACU G CCUAAUUC 2265 GAATTAGG GGCTAGCTACAACGA AGTTCTTG 3017 530 ACUGCCUA A UUCAGGAC 2730 GTCCTGAA GGCTAGCTACAACGA TAGGCAGT 3018 537 AAUUCAGG A CCUCCACA 2731 TGTGGAGG GGCTAGCTACAACGA CCTGAATT 3019 543 GGACCUCC A CAUGAUAG 1377 CTATCATG GGCTAGCTACAACGA GGAGGTCC 3020 545 ACCUCCAC A UGAUAGGA 1378 TCCTATCA GGCTAGCTACAACGA GTGGAGGT 3021 548 UCCACAUG A UAGGAGGU 2732 ACCTCCTA GGCTAGCTACAACGA CATGTGGA 3022 555 GAUAGGAG G UUUACAUU 2266 AATGTAAA GGCTAGCTACAACGA CTCCTATC 3023 559 GGAGGUUU A CAUUUCAA 132 TTGAAATG GGCTAGCTACAACGA AAACCTCC 3024 561 AGGUUUAC A UUUCAAGU 1379 ACTTGAAA GGCTAGCTACAACGA GTAAACCT 3025

568 CAUUUCAA G UUAUAAUA 2267 TATTATAA GGCTAGCTACAACGA TTGAAATG 3026 571 UUCAAGUU A UAAUAGAU 137 ATCTATTA GGCTAGCTACAACGA AACTTGAA 3027 574 AAGUUAUA A UAGAUGGA 2733 TCCATCTA GGCTAGCTACAACGA TATAACTT 3028 578 UAUAAUAG A UGGAAGAG 2734 CTCTTCCA GGCTAGCTACAACGA CTATTATA 3029 588 GGAAGAGA A UUUCCAGA 2735 TCTGGAAA GGCTAGCTACAACGA TCTCTTCC 3030 599 UCCAGAAG G UGAAGGUA 2268 TACCTTCA GGCTAGCTACAACGA CTTCTGGA 3031 605 AGGUGAAG G UAGAUCAA 2269 TTGATCTA GGCTAGCTACAACGA CTTCACCT 3032 609 GAAGGUAG A UCAAAGAA 2736 TTCTTTGA GGCTAGCTACAACGA CTACCTTC 3033 622 AGAAGGAA G CAAAAAAU 2270 ATTTTTTG GGCTAGCTACAACGA TTCCTTCT 3034 629 AGCAAAAA A UGCCGCAG 2737 CTGCGGCA GGCTAGCTACAACGA TTTTTGCT 3035 631 CAAAAAAU G CCGCAGCC 2271 GGCTGCGG GGCTAGCTACAACGA ATTTTTTG 3036 634 AAAAUGCC G CAGCCAAA 2272 TTTGGCTG GGCTAGCTACAACGA GGCATTTT 3037 637 AUGCCGCA G CCAAAUUA 2273 TAATTTGG GGCTAGCTACAACGA TGCGGCAT 3038 642 GCAGCCAA A UUAGCUGU 2738 ACAGCTAA GGCTAGCTACAACGA TTGGCTGC 3039 646 CCAAAUUA G CUGUUGAG 2274 CTCAACAG GGCTAGCTACAACGA TAATTTGG 3040 649 AAUUAGCU G UUGAGAUA 2275 TATCTCAA GGCTAGCTACAACGA AGCTAATT 3041 655 CUGUUGAG A UACUUAAU 2739 ATTAAGTA GGCTAGCTACAACGA CTCAACAG 3042 657 GUUGAGAU A CUUAAUAA 148 TTATTAAG GGCTAGCTACAACGA ATCTCAAC 3043 662 GAUACUUA A UAAGGAAA 2740 TTTCCTTA GGCTAGCTACAACGA TAAGTATC 3044 676 AAAAGAAG G CAGUUAGU 2276 ACTAACTG GGCTAGCTACAACGA CTTCTTTT 3045 679 AGAAGGCA G UUAGUCCU 2277 AGGACTAA GGCTAGCTACAACGA TGCCTTCT 3046 683 GGCAGUUA G UCCUUUAU 2278 ATAAAGGA GGCTAGCTACAACGA TAACTGCC 3047 690 AGUCCUUU A UUAUUGAC 157 GTCAATAA GGCTAGCTACAACGA AAAGGACT 3048 693 CCUUUAUU A UUGACAAC 159 GTTGTCAA GGCTAGCTACAACGA AATAAAGG 3049 697 UAUUAUUG A CAACAACG 2741 CGTTGTTG GGCTAGCTACAACGA CAATAATA 3050 700 UAUUGACA A CAACGAAU 2742 ATTCGTTG GGCTAGCTACAACGA TGTCAATA 3051 703 UGACAACA A CGAAUUCU 2743 AGAATTCG GGCTAGCTACAACGA TGTTGTCA 3052 707 AACAACGA A UUCUUCAG 2744 CTGAAGAA GGCTAGCTACAACGA TCGTTGTT 3053 720 UCAGAAGG A UUAUCCAU 2745 ATGGATAA GGCTAGCTACAACGA CCTTCTGA 3054 723 GAAGGAUU A UCCAUGGG 166 CCCATGGA GGCTAGCTACAACGA AATCCTTC 3055 727 GAUUAUCC A UGGGGAAU 1399 ATTCCCCA GGCTAGCTACAACGA GGATAATC 3056 734 CAUGGGGA A UUACAUAG 2746 CTATGTAA GGCTAGCTACAACGA TCCCCATG 3057 737 GGGGAAUU A CAUAGGCC 169 GGCCTATG GGCTAGCTACAACGA AATTCCCC 3058 739 GGAAUUAC A UAGGCCUU 1400 AAGGCCTA GGCTAGCTACAACGA GTAATTCC 3059 743 UUACAUAG G CCUUAUCA 2279 TGATAAGG GGCTAGCTACAACGA CTATGTAA 3060 748 UAGGCCUU A UCAAUAGA 172 TCTATTGA GGCTAGCTACAACGA AAGGCCTA 3061 752 CCUUAUCA A UAGAAUUG 2747 CAATTCTA GGCTAGCTACAACGA TGATAAGG 3062 757 UCAAUAGA A UUGCCCAG 2748 CTGGGCAA GGCTAGCTACAACGA TCTATTGA 3063 760 AUAGAAUU G CCCAGAAG 2280 CTTCTGGG GGCTAGCTACAACGA AATTCTAT 3064 774 AAGAAAAG A CUAACUGU 2749 ACAGTTAG GGCTAGCTACAACGA CTTTTCTT 3065 778 AAAGACUA A CUGUAAAU 2750 ATTTACAG GGCTAGCTACAACGA TAGTCTTT 3066 781 GACUAACU G UAAAUUAU 2281 ATAATTTA GGCTAGCTACAACGA AGTTAGTC 3067 785 AACUGUAA A UUAUGAAC 2751 GTTCATAA GGCTAGCTACAACGA TTACAGTT 3068 788 UGUAAAUU A UGAACAGU 179 ACTGTTCA GGCTAGCTACAACGA AATTTACA 3069 792 AAUUAUGA A CAGUGUGC 2752 GCACACTG GGCTAGCTACAACGA TCATAATT 3070 795 UAUGAACA G UGUGCAUC 2282 GATGCACA GGCTAGCTACAACGA TGTTCATA 3071 797 UGAACAGU G UGCAUCGG 2283 CCGATGCA GGCTAGCTACAACGA ACTGTTCA 3072 799 AACAGUGU G CAUCGGGG 2284 CCCCGATG GGCTAGCTACAACGA ACACTGTT 3073 801 CAGUGUGC A UCGGGGGU 1410 ACCCCCGA GGCTAGCTACAACGA GCACACTG 3074 808 CAUCGGGG G UGCAUGGG 2285 CCCATGCA GGCTAGCTACAACGA CCCCGATG 3075 810 UCGGGGGU G CAUGGGCC 2286 GGCCCATG GGCTAGCTACAACGA ACCCCCGA 3076 812 GGGGGUGC A UGGGCCAG 1411 CTGGCCCA GGCTAGCTACAACGA GCACCCCC 3077 816 GUGCAUGG G CCAGAAGG 2287 CCTTCTGG GGCTAGCTACAACGA CCATGCAC 3078 825 CCAGAAGG A UUUCAUUA 2753 TAATGAAA GGCTAGCTACAACGA CCTTCTGG 3079 830 AGGAUUUC A UUAUAAAU 1414 ATTTATAA GGCTAGCTACAACGA GAAATCCT 3080 833 AUUUCAUU A UAAAUGCA 185 TGCATTTA GGCTAGCTACAACGA AATGAAAT 3081 837 CAUUAUAA A UGCAAAAU 2754 ATTTTGCA GGCTAGCTACAACGA TTATAATG 3082 839 UUAUAAAU G CAAAAUGG 2288 CCATTTTG GGCTAGCTACAACGA ATTTATAA 3083 844 AAUGCAAA A UGGGACAG 2755 CTGTCCCA GGCTAGCTACAACGA TTTGCATT 3084 849 AAAAUGGG A CAGAAAGA 2756 TCTTTCTG GGCTAGCTACAACGA CCCATTTT 3085 858 CAGAAAGA A UAUAGUAU 2757 ATACTATA GGCTAGCTACAACGA TCTTTCTG 3086 860 GAAAGAAU A UAGUAUUG 187 CAATACTA GGCTAGCTACAACGA ATTCTTTC 3087 863 AGAAUAUA G UAUUGGUA 2289 TACCAATA GGCTAGCTACAACGA TATATTCT 3088 865 AAUAUAGU A UUGGUACA 189 TGTACCAA GGCTAGCTACAACGA ACTATATT 3089 869 UAGUAUUG G UACAGGUU 2290 AACCTGTA GGCTAGCTACAACGA CAATACTA 3090 871 GUAUUGGU A CAGGUUCU 191 AGAACCTG GGCTAGCTACAACGA ACCAATAC 3091 875 UGGUACAG G UUCUACUA 2291 TAGTAGAA GGCTAGCTACAACGA CTGTACCA 3092 880 CAGGUUCU A CUAAACAG 194 CTGTTTAG GGCTAGCTACAACGA AGAACCTG 3093 885 UCUACUAA A CAGGAAGC 2758 GCTTCCTG GGCTAGCTACAACGA TTAGTAGA 3094 892 AACAGGAA G CAAAACAA 2292 TTGTTTTG GGCTAGCTACAACGA TTCCTGTT 3095 897 GAAGCAAA A CAAUUGGC 2759 GCCAATTG GGCTAGCTACAACGA TTTGCTTC 3096 900 GCAAAACA A UUGGCCGC 2760 GCGGCCAA GGCTAGCTACAACGA TGTTTTGC 3097 904 AACAAUUG G CCGCUAAA 2293 TTTAGCGG GGCTAGCTACAACGA CAATTGTT 3098 907 AAUUGGCC G CUAAACUU 2294 AAGTTTAG GGCTAGCTACAACGA GGCCAATT 3099 912 GCCGCUAA A CUUGCAUA 2761 TATGCAAG GGCTAGCTACAACGA TTAGCGGC 3100 916 CUAAACUU G CAUAUCUU 2295 AAGATATG GGCTAGCTACAACGA AAGTTTAG 3101 918 AAACUUGC A UAUCUUCA 1426 TGAAGATA GGCTAGCTACAACGA GCAAGTTT 3102 920 ACUUGCAU A UCUUCAGA 199 TCTGAAGA GGCTAGCTACAACGA ATGCAAGT 3103 928 AUCUUCAG A UAUUAUCA 2762 TGATAATA GGCTAGCTACAACGA CTGAAGAT 3104 930 CUUCAGAU A UUAUCAGA 203 TCTGATAA GGCTAGCTACAACGA ATCTGAAG 3105 933 CAGAUAUU A UCAGAAGA 205 TCTTCTGA GGCTAGCTACAACGA AATATCTG 3106 943 CAGAAGAA A CCUCAGUG 2763 CACTGAGG GGCTAGCTACAACGA TTCTTCTG 3107 949 AAACCUCA G UGAAAUCU 2296 AGATTTCA GGCTAGCTACAACGA TGAGGTTT 3108 954 UCAGUGAA A UCUGACUA 2764 TAGTCAGA GGCTAGCTACAACGA TTCACTGA 3109 959 GAAAUCUG A CUACCUGU 2765 ACAGGTAG GGCTAGCTACAACGA CAGATTTC 3110 962 AUCUGACU A CCUGUCCU 209 AGGACAGG GGCTAGCTACAACGA AGTCAGAT 3111 966 GACUACCU G UCCUCUGG 2297 CCAGAGGA GGCTAGCTACAACGA AGGTAGTC 3112 974 GUCCUCUG G UUCUUUUG 2298 CAAAAGAA GGCTAGCTACAACGA CAGAGGAC 3113 982 GUUCUUUU G CUACUACG 2299 CGTAGTAG GGCTAGCTACAACGA AAAAGAAC 3114 985 CUUUUGCU A CUACGUGU 217 ACACGTAG GGCTAGCTACAACGA AGCAAAAG 3115 988 UUGCUACU A CGUGUGAG 218 CTCACACG GGCTAGCTACAACGA AGTAGCAA 3116 990 GCUACUAC G UGUGAGUC 2300 GACTCACA GGCTAGCTACAACGA GTAGTAGC 3117 992 UACUACGU G UGAGUCCC 2301 GGGACTCA GGCTAGCTACAACGA ACGTAGTA 3118 996 ACGUGUGA G UCCCAAAG 2302 CTTTGGGA GGCTAGCTACAACGA TCACACGT 3119 1004 GUCCCAAA G CAACUCUU 2303 AAGAGTTG GGCTAGCTACAACGA TTTGGGAC 3120 1007 CCAAAGCA A CUCUUUAG 2766 CTAAAGAG GGCTAGCTACAACGA TGCTTTGG 3121 1015 ACUCUUUA G UGACCAGC 2304 GCTGGTCA GGCTAGCTACAACGA TAAAGAGT 3122 1018 CUUUAGUG A CCAGCACA 2767 TGTGCTGG GGCTAGCTACAACGA CACTAAAG 3123 1022 AGUGACCA G CACACUCG 2305 CGAGTGTG GGCTAGCTACAACGA TGGTCACT 3124 1024 UGACCAGC A CACUCGCU 1451 AGCGAGTG GGCTAGCTACAACGA GCTGGTCA 3125 1026 ACCAGCAC A CUCGCUUC 1452 GAAGCGAG GGCTAGCTACAACGA GTGCTGGT 3126 1030 GCACACUC G CUUCUGAA 2306 TTCAGAAG GGCTAGCTACAACGA GAGTGTGC 3127 1038 GCUUCUGA A UCAUCAUC 2768 GATGATGA GGCTAGCTACAACGA TCAGAAGC 3128 1041 UCUGAAUC A UCAUCUGA 1456 TCAGATGA GGCTAGCTACAACGA GATTCAGA 3129 1044 GAAUCAUC A UCUGAAGG 1457 CCTTCAGA GGCTAGCTACAACGA GATGATTC 3130 1052 AUCUGAAG G UGACUUCU 2307 AGAAGTCA GGCTAGCTACAACGA CTTCAGAT 3131 1055 UGAAGGUG A CUUCUCAG 2769 CTGAGAAG GGCTAGCTACAACGA CACCTTCA 3132 1063 ACUUCUCA G CAGAUACA 2308 TGTATCTG GGCTAGCTACAACGA TGAGAAGT 3133 1067 CUCAGCAG A UACAUCAG 2770 CTGATGTA GGCTAGCTACAACGA CTGCTGAG 3134 1069 CAGCAGAU A CAUCAGAG 233 CTCTGATG GGCTAGCTACAACGA ATCTGCTG 3135 1071 GCAGAUAC A UCAGAGAU 1463 ATCTCTGA GGCTAGCTACAACGA GTATCTGC 3136 1078 CAUCAGAG A UAAAUUCU 2771 AGAATTTA GGCTAGCTACAACGA CTCTGATG 3137 1082 AGAGAUAA A UUCUAACA 2772 TGTTAGAA GGCTAGCTACAACGA TTATCTCT 3138 1088 AAAUUCUA A CAGUGACA 2773 TGTCACTG GGCTAGCTACAACGA TAGAATTT 3139 1091 UUCUAACA G UGACAGUU 2309 AACTGTCA GGCTAGCTACAACGA TGTTAGAA 3140 1094 UAACAGUG A CAGUUUAA 2774 TTAAACTG GGCTAGCTACAACGA CACTGTTA 3141 1097 CAGUGACA G UUUAAACA 2310 TGTTTAAA GGCTAGCTACAACGA TGTCACTG 3142 1103 CAGUUUAA A CAGUUCUU 2775 AAGAACTG GGCTAGCTACAACGA TTAAACTG 3143 1106 UUUAAACA G UUCUUCGU 2311 ACGAAGAA GGCTAGCTACAACGA TGTTTAAA 3144 1113 AGUUCUUC G UUGCUUAU 2312 ATAAGCAA GGCTAGCTACAACGA GAAGAACT 3145 1116 UCUUCGUU G CUUAUGAA 2313 TTCATAAG GGCTAGCTACAACGA AACGAAGA 3146 1120 CGUUGCUU A UGAAUGGU 248 ACCATTCA GGCTAGCTACAACGA AAGCAACG 3147 1124 GCUUAUGA A UGGUCUCA 2776 TGAGACCA GGCTAGCTACAACGA TCATAAGC 3148 1127 UAUGAAUG G UCUCAGAA 2314 TTCTGAGA GGCTAGCTACAACGA CATTCATA 3149 1136 UCUCAGAA A UAAUCAAA 2777 TTTGATTA GGCTAGCTACAACGA TTCTGAGA 3150

1139 CAGAAAUA A UCAAAGGA 2778 TCCTTTGA GGCTAGCTACAACGA TATTTCTG 3151 1150 AAAGGAAG G CAAAAAGA 2315 TCTTTTTG GGCTAGCTACAACGA CTTCCTTT 3152 1158 GCAAAAAG A UCUUUGGC 2779 GCCAAAGA GGCTAGCTACAACGA CTTTTTGC 3153 1165 GAUCUUUG G CACCCAGA 2316 TCTGGGTG GGCTAGCTACAACGA CAAAGATC 3154 1167 UCUUUGGC A CCCAGAUU 1476 AATCTGGG GGCTAGCTACAACGA GCCAAAGA 3155 1173 GCACCCAG A UUUGACCU 2780 AGGTCAAA GGCTAGCTACAACGA CTGGGTGC 3156 1178 CAGAUUUG A CCUUCCUG 2781 CAGGAAGG GGCTAGCTACAACGA CAAATCTG 3157 1187 CCUUCCUG A CAUGAAAG 2782 CTTTCATG GGCTAGCTACAACGA CAGGAAGG 3158 1189 UUCCUGAC A UGAAAGAA 1484 TTCTTTCA GGCTAGCTACAACGA GTCAGGAA 3159 1198 UGAAAGAA A CAAAGUAU 2783 ATACTTTG GGCTAGCTACAACGA TTCTTTCA 3160 1203 GAAACAAA G UAUACUGU 2317 ACAGTATA GGCTAGCTACAACGA TTTGTTTC 3161 1205 AACAAAGU A UACUGUGG 260 CCACAGTA GGCTAGCTACAACGA ACTTTGTT 3162 1207 CAAAGUAU A CUGUGGAC 261 GTCCACAG GGCTAGCTACAACGA ATACTTTG 3163 1210 AGUAUACU G UGGACAAG 2318 CTTGTCCA GGCTAGCTACAACGA AGTATACT 3164 1214 UACUGUGG A CAAGAGGU 2784 ACCTCTTG GGCTAGCTACAACGA CCACAGTA 3165 1221 GACAAGAG G UUUGGCAU 2319 ATGCCAAA GGCTAGCTACAACGA CTCTTGTC 3166 1226 GAGGUUUG G CAUGGAUU 2320 AATCCATG GGCTAGCTACAACGA CAAACCTC 3167 1228 GGUUUGGC A UGGAUUUU 1488 AAAATCCA GGCTAGCTACAACGA GCCAAACC 3168 1232 UGGCAUGG A UUUUAAAG 2785 CTTTAAAA GGCTAGCTACAACGA CCATGCCA 3169 1243 UUAAAGAA A UAGAAUUA 2786 TAATTCTA GGCTAGCTACAACGA TTCTTTAA 3170 1248 GAAAUAGA A UUAAUUGG 2787 CCAATTAA GGCTAGCTACAACGA TCTATTTC 3171 1252 UAGAAUUA A UUGGCUCA 2788 TGAGCCAA GGCTAGCTACAACGA TAATTCTA 3172 1256 AUUAAUUG G CUCAGGUG 2321 CACCTGAG GGCTAGCTACAACGA CAATTAAT 3173 1262 UGGCUCAG G UGGAUUUG 2322 CAAATCCA GGCTAGCTACAACGA CTGAGCCA 3174 1266 UCAGGUGG A UUUGGCCA 2789 TGGCCAAA GGCTAGCTACAACGA CCACCTGA 3175 1271 UGGAUUUG G CCAAGUUU 2323 AAACTTGG GGCTAGCTACAACGA CAAATCCA 3176 1276 UUGGCCAA G UUUUCAAA 2324 TTTGAAAA GGCTAGCTACAACGA TTGGCCAA 3177 1285 UUUUCAAA G CAAAACAC 2325 GTGTTTTG GGCTAGCTACAACGA TTTGAAAA 3178 1290 AAAGCAAA A CACAGAAU 2790 ATTCTGTG GGCTAGCTACAACGA TTTGCTTT 3179 1292 AGCAAAAC A CAGAAUUG 1495 CAATTCTG GGCTAGCTACAACGA GTTTTGCT 3180 1297 AACACAGA A UUGACGGA 2791 TCCGTCAA GGCTAGCTACAACGA TCTGTGTT 3181 1301 CAGAAUUG A CGGAAAGA 2792 TCTTTCCG GGCTAGCTACAACGA CAATTCTG 3182 1309 ACGGAAAG A CUUACGUU 2793 AACGTAAG GGCTAGCTACAACGA CTTTCCGT 3183 1313 AAAGACUU A CGUUAUUA 281 TAATAACG GGCTAGCTACAACGA AAGTCTTT 3184 1315 AGACUUAC G UUAUUAAA 2326 TTTAATAA GGCTAGCTACAACGA GTAAGTCT 3185 1318 CUUACGUU A UUAAACGU 283 ACGTTTAA GGCTAGCTACAACGA AACGTAAG 3186 1323 GUUAUUAA A CGUGUUAA 2794 TTAACACG GGCTAGCTACAACGA TTAATAAC 3187 1325 UAUUAAAC G UGUUAAAU 2327 ATTTAACA GGCTAGCTACAACGA GTTTAATA 3188 1327 UUAAACGU G UUAAAUAU 2328 ATATTTAA GGCTAGCTACAACGA ACGTTTAA 3189 1332 CGUGUUAA A UAUAAUAA 2795 TTATTATA GGCTAGCTACAACGA TTAACACG 3190 1334 UGUUAAAU A UAAUAACG 288 CGTTATTA GGCTAGCTACAACGA ATTTAACA 3191 1337 UAAAUAUA A UAACGAGA 2796 TCTCGTTA GGCTAGCTACAACGA TATATTTA 3192 1340 AUAUAAUA A CGAGAAGG 2797 CCTTCTCG GGCTAGCTACAACGA TATTATAT 3193 1348 ACGAGAAG G CGGAGCGU 2329 ACGCTCCG GGCTAGCTACAACGA CTTCTCGT 3194 1353 AAGGCGGA G CGUGAAGU 2330 ACTTCACG GGCTAGCTACAACGA TCCGCCTT 3195 1355 GGCGGAGC G UGAAGUAA 2331 TTACTTCA GGCTAGCTACAACGA GCTCCGCC 3196 1360 AGCGUGAA G UAAAAGCA 2332 TGCTTTTA GGCTAGCTACAACGA TTCACGCT 3197 1366 AAGUAAAA G CAUUGGCA 2333 TGCCAATG GGCTAGCTACAACGA TTTTACTT 3198 1368 GUAAAAGC A UUGGCAAA 1498 TTTGCCAA GGCTAGCTACAACGA GCTTTTAC 3199 1372 AAGCAUUG G CAAAACUU 2334 AAGTTTTG GGCTAGCTACAACGA CAATGCTT 3200 1377 UUGGCAAA A CUUGAUCA 2798 TGATCAAG GGCTAGCTACAACGA TTTGCCAA 3201 1382 AAAACUUG A UCAUGUAA 2799 TTACATGA GGCTAGCTACAACGA CAAGTTTT 3202 1385 ACUUGAUC A UGUAAAUA 1501 TATTTACA GGCTAGCTACAACGA GATCAAGT 3203 1387 UUGAUCAU G UAAAUAUU 2335 AATATTTA GGCTAGCTACAACGA ATGATCAA 3204 1391 UCAUGUAA A UAUUGUUC 2800 GAACAATA GGCTAGCTACAACGA TTACATGA 3205 1393 AUGUAAAU A UUGUUCAC 296 GTGAACAA GGCTAGCTACAACGA ATTTACAT 3206 1396 UAAAUAUU G UUCACUAC 2336 GTAGTGAA GGCTAGCTACAACGA AATATTTA 3207 1400 UAUUGUUC A CUACAAUG 1502 CATTGTAG GGCTAGCTACAACGA GAACAATA 3208 1403 UGUUCACU A CAAUGGCU 300 AGCCATTG GGCTAGCTACAACGA AGTGAACA 3209 1406 UCACUACA A UGGCUGUU 2801 AACAGCCA GGCTAGCTACAACGA TGTAGTGA 3210 1409 CUACAAUG G CUGUUGGG 2337 CCCAACAG GGCTAGCTACAACGA CATTGTAG 3211 1412 CAAUGGCU G UUGGGAUG 2338 CATCCCAA GGCTAGCTACAACGA AGCCATTG 3212 1418 CUGUUGGG A UGGAUUUG 2802 CAAATCCA GGCTAGCTACAACGA CCCAACAG 3213 1422 UGGGAUGG A UUUGAUUA 2803 TAATCAAA GGCTAGCTACAACGA CCATCCCA 3214 1427 UGGAUUUG A UUAUGAUC 2804 GATCATAA GGCTAGCTACAACGA CAAATCCA 3215 1430 AUUUGAUU A UGAUCCUG 305 CAGGATCA GGCTAGCTACAACGA AATCAAAT 3216 1433 UGAUUAUG A UCCUGAGA 2805 TCTCAGGA GGCTAGCTACAACGA CATAATCA 3217 1441 AUCCUGAG A CCAGUGAU 2806 ATCACTGG GGCTAGCTACAACGA CTCAGGAT 3218 1445 UGAGACCA G UGAUGAUU 2339 AATCATCA GGCTAGCTACAACGA TGGTCTCA 3219 1448 GACCAGUG A UGAUUCUC 2807 GAGAATCA GGCTAGCTACAACGA CACTGGTC 3220 1451 CAGUGAUG A UUCUCUUG 2808 CAAGAGAA GGCTAGCTACAACGA CATCACTG 3221 1463 UCUUGAGA G CAGUGAUU 2340 AATCACTG GGCTAGCTACAACGA TCTCAAGA 3222 1466 UGAGAGCA G UGAUUAUG 2341 CATAATCA GGCTAGCTACAACGA TGCTCTCA 3223 1469 GAGCAGUG A UUAUGAUC 2809 GATCATAA GGCTAGCTACAACGA CACTGCTC 3224 1472 CAGUGAUU A UGAUCCUG 312 CAGGATCA GGCTAGCTACAACGA AATCACTG 3225 1475 UGAUUAUG A UCCUGAGA 2805 TCTCAGGA GGCTAGCTACAACGA CATAATCA 3217 1484 UCCUGAGA A CAGCAAAA 2810 TTTTGCTG GGCTAGCTACAACGA TCTCAGGA 3226 1487 UGAGAACA G CAAAAAUA 2342 TATTTTTG GGCTAGCTACAACGA TGTTCTCA 3227 1493 CAGCAAAA A UAGUUCAA 2811 TTGAACTA GGCTAGCTACAACGA TTTTGCTG 3228 1496 CAAAAAUA G UUCAAGGU 2343 ACCTTGAA GGCTAGCTACAACGA TATTTTTG 3229 1503 AGUUCAAG G UCAAAGAC 2344 GTCTTTGA GGCTAGCTACAACGA CTTGAACT 3230 1510 GGUCAAAG A CUAAGUGC 2812 GCACTTAG GGCTAGCTACAACGA CTTTGACC 3231 1515 AAGACUAA G UGCCUUUU 2345 AAAAGGCA GGCTAGCTACAACGA TTAGTCTT 3232 1517 GACUAAGU G CCUUUUCA 2346 TGAAAAGG GGCTAGCTACAACGA ACTTAGTC 3233 1525 GCCUUUUC A UCCAAAUG 1522 CATTTGGA GGCTAGCTACAACGA GAAAAGGC 3234 1531 UCAUCCAA A UGGAAUUC 2813 GAATTCCA GGCTAGCTACAACGA TTGGATGA 3235 1536 CAAAUGGA A UUCUGUGA 2814 TCACAGAA GGCTAGCTACAACGA TCCATTTG 3236 1541 GGAAUUCU G UGAUAAAG 2347 CTTTATCA GGCTAGCTACAACGA AGAATTCC 3237 1544 AUUCUGUG A UAAAGGGA 2815 TCCCTTTA GGCTAGCTACAACGA CACAGAAT 3238 1552 AUAAAGGG A CCUUGGAA 2816 TTCCAAGG GGCTAGCTACAACGA CCCTTTAT 3239 1560 ACCUUGGA A CAAUGGAU 2817 ATCCATTG GGCTAGCTACAACGA TCCAAGGT 3240 1563 UUGGAACA A UGGAUUGA 2818 TCAATCCA GGCTAGCTACAACGA TGTTCCAA 3241 1567 AACAAUGG A UUGAAAAA 2819 TTTTTCAA GGCTAGCTACAACGA CCATTGTT 3242 1583 AAGAAGAG G CGAGAAAC 2348 GTTTCTCG GGCTAGCTACAACGA CTCTTCTT 3243 1590 GGCGAGAA A CUAGACAA 2820 TTGTCTAG GGCTAGCTACAACGA TTCTCGCC 3244 1595 GAAACUAG A CAAAGUUU 2821 AAACTTTG GGCTAGCTACAACGA CTAGTTTC 3245 1600 UAGACAAA G UUUUGGCU 2349 AGCCAAAA GGCTAGCTACAACGA TTTGTCTA 3246 1606 AAGUUUUG G CUUUGGAA 2350 TTCCAAAG GGCTAGCTACAACGA CAAAACTT 3247 1614 GCUUUGGA A CUCUUUGA 2822 TCAAAGAG GGCTAGCTACAACGA TCCAAAGC 3248 1623 CUCUUUGA A CAAAUAAC 2823 GTTATTTG GGCTAGCTACAACGA TCAAAGAG 3249 1627 UUGAACAA A UAACAAAA 2824 TTTTGTTA GGCTAGCTACAACGA TTGTTCAA 3250 1630 AACAAAUA A CAAAAGGG 2825 CCCTTTTG GGCTAGCTACAACGA TATTTGTT 3251 1639 CAAAAGGG G UGGAUUAU 2351 ATAATCCA GGCTAGCTACAACGA CCCTTTTG 3252 1643 AGGGGUGG A UUAUAUAC 2826 GTATATAA GGCTAGCTACAACGA CCACCCCT 3253 1646 GGUGGAUU A UAUACAUU 340 AATGTATA GGCTAGCTACAACGA AATCCACC 3254 1648 UGGAUUAU A UACAUUCA 341 TGAATGTA GGCTAGCTACAACGA ATAATCCA 3255 1650 GAUUAUAU A CAUUCAAA 342 TTTGAATG GGCTAGCTACAACGA ATATAATC 3256 1652 UUAUAUAC A UUCAAAAA 1536 TTTTTGAA GGCTAGCTACAACGA GTATATAA 3257 1662 UCAAAAAA A UUAAUUCA 2827 TGAATTAA GGCTAGCTACAACGA TTTTTTGA 3258 1666 AAAAAUUA A UUCAUAGA 2828 TCTATGAA GGCTAGCTACAACGA TAATTTTT 3259 1670 AUUAAUUC A UAGAGAUC 1538 GATCTCTA GGCTAGCTACAACGA GAATTAAT 3260 1676 UCAUAGAG A UCUUAAGC 2829 GCTTAAGA GGCTAGCTACAACGA CTCTATGA 3261 1683 GAUCUUAA G CCAAGUAA 2352 TTACTTGG GGCTAGCTACAACGA TTAAGATC 3262 1688 UAAGCCAA G UAAUAUAU 2353 ATATATTA GGCTAGCTACAACGA TTGGCTTA 3263 1691 GCCAAGUA A UAUAUUCU 2830 AGAATATA GGCTAGCTACAACGA TACTTGGC 3264 1693 CAAGUAAU A UAUUCUUA 354 TAAGAATA GGCTAGCTACAACGA ATTACTTG 3265 1695 AGUAAUAU A UUCUUAGU 355 ACTAAGAA GGCTAGCTACAACGA ATATTACT 3266 1702 UAUUCUUA G UAGAUACA 2354 TGTATCTA GGCTAGCTACAACGA TAAGAATA 3267 1706 CUUAGUAG A UACAAAAC 2831 GTTTTGTA GGCTAGCTACAACGA CTACTAAG 3268 1708 UAGUAGAU A CAAAACAA 361 TTGTTTTG GGCTAGCTACAACGA ATCTACTA 3269 1713 GAUACAAA A CAAGUAAA 2832 TTTACTTG GGCTAGCTACAACGA TTTGTATC 3270 1717 CAAAACAA G UAAAGAUU 2355 AATCTTTA GGCTAGCTACAACGA TTGTTTTG 3271 1723 AAGUAAAG A UUGGAGAC 2833 GTCTCCAA GGCTAGCTACAACGA CTTTACTT 3272 1730 GAUUGGAG A CUUUGGAC 2834 GTCCAAAG GGCTAGCTACAACGA CTCCAATC 3273 1737 GACUUUGG A CUUGUAAC 2835 GTTACAAG GGCTAGCTACAACGA CCAAAGTC 3274 1741 UUGGACUU G UAACAUCU 2356 AGATGTTA GGCTAGCTACAACGA AAGTCCAA 3275

1744 GACUUGUA A CAUCUCUG 2836 CAGAGATG GGCTAGCTACAACGA TACAAGTC 3276 1746 CUUGUAAC A UCUCUGAA 1547 TTCAGAGA GGCTAGCTACAACGA GTTACAAG 3277 1757 UCUGAAAA A UGAUGGAA 2837 TTCCATCA GGCTAGCTACAACGA TTTTCAGA 3278 1760 GAAAAAUG A UGGAAAGC 2838 GCTTTCCA GGCTAGCTACAACGA CATTTTTC 3279 1767 GAUGGAAA G CGAACAAG 2357 CTTGTTCG GGCTAGCTACAACGA TTTCCATC 3280 1771 GAAAGCGA A CAAGGAGU 2839 ACTCCTTG GGCTAGCTACAACGA TCGCTTTC 3281 1778 AACAAGGA G UAAGGGAA 2358 TTCCCTTA GGCTAGCTACAACGA TCCTTGTT 3282 1786 GUAAGGGA A CUUUGCGA 2840 TCGCAAAG GGCTAGCTACAACGA TCCCTTAC 3283 1791 GGAACUUU G CGAUACAU 2359 ATGTATCG GGCTAGCTACAACGA AAAGTTCC 3284 1794 ACUUUGCG A UACAUGAG 2841 CTCATGTA GGCTAGCTACAACGA CGCAAAGT 3285 1796 UUUGCGAU A CAUGAGCC 373 GGCTCATG GGCTAGCTACAACGA ATCGCAAA 3286 1798 UGCGAUAC A UGAGCCCA 1552 TGGGCTCA GGCTAGCTACAACGA GTATCGCA 3287 1802 AUACAUGA G CCCAGAAC 2360 GTTCTGGG GGCTAGCTACAACGA TCATGTAT 3288 1809 AGCCCAGA A CAGAUUUC 2842 GAAATCTG GGCTAGCTACAACGA TCTGGGCT 3289 1813 CAGAACAG A UUUCUUCG 2843 CGAAGAAA GGCTAGCTACAACGA CTGTTCTG 3290 1821 AUUUCUUC G CAAGACUA 2361 TAGTCTTG GGCTAGCTACAACGA GAAGAAAT 3291 1826 UUCGCAAG A CUAUGGAA 2844 TTCCATAG GGCTAGCTACAACGA CTTGCGAA 3292 1829 GCAAGACU A UGGAAAGG 379 CCTTTCCA GGCTAGCTACAACGA AGTCTTGC 3293 1840 GAAAGGAA G UGGACCUC 2362 GAGGTCCA GGCTAGCTACAACGA TTCCTTTC 3294 1844 GGAAGUGG A CCUCUACG 2845 CGTAGAGG GGCTAGCTACAACGA CCACTTCC 3295 1850 GGACCUCU A CGCUUUGG 381 CCAAAGCG GGCTAGCTACAACGA AGAGGTCC 3296 1852 ACCUCUAC G CUUUGGGG 2363 CCCCAAAG GGCTAGCTACAACGA GTAGAGGT 3297 1860 GCUUUGGG G CUAAUUCU 2364 AGAATTAG GGCTAGCTACAACGA CCCAAAGC 3298 1864 UGGGGCUA A UUCUUGCU 2846 AGCAAGAA GGCTAGCTACAACGA TAGCCCCA 3299 1870 UAAUUCUU G CUGAACUU 2365 AAGTTCAG GGCTAGCTACAACGA AAGAATTA 3300 1875 CUUGCUGA A CUUCUUCA 2847 TGAAGAAG GGCTAGCTACAACGA TCAGCAAG 3301 1883 ACUUCUUC A UGUAUGUG 1569 CACATACA GGCTAGCTACAACGA GAAGAAGT 3302 1885 UUCUUCAU G UAUGUGAC 2366 GTCACATA GGCTAGCTACAACGA ATGAAGAA 3303 1887 CUUCAUGU A UGUGACAC 392 GTGTCACA GGCTAGCTACAACGA ACATGAAG 3304 1889 UCAUGUAU G UGACACUG 2367 CAGTGTCA GGCTAGCTACAACGA ATACATGA 3305 1892 UGUAUGUG A CACUGCUU 2848 AAGCAGTG GGCTAGCTACAACGA CACATACA 3306 1894 UAUGUGAC A CUGCUUUU 1570 AAAAGCAG GGCTAGCTACAACGA GTCACATA 3307 1897 GUGACACU G CUUUUGAA 2368 TTCAAAAG GGCTAGCTACAACGA AGTGTCAC 3308 1906 CUUUUGAA A CAUCAAAG 2849 CTTTGATG GGCTAGCTACAACGA TTCAAAAG 3309 1908 UUUGAAAC A UCAAAGUU 1573 AACTTTGA GGCTAGCTACAACGA GTTTCAAA 3310 1914 ACAUCAAA G UUUUUCAC 2369 GTGAAAAA GGCTAGCTACAACGA TTTGATGT 3311 1921 AGUUUUUC A CAGACCUA 1575 TAGGTCTG GGCTAGCTACAACGA GAAAAACT 3312 1925 UUUCACAG A CCUACGGG 2850 CCCGTAGG GGCTAGCTACAACGA CTGTGAAA 3313 1929 ACAGACCU A CGGGAUGG 402 CCATCCCG GGCTAGCTACAACGA AGGTCTGT 3314 1934 CCUACGGG A UGGCAUCA 2851 TGATGCCA GGCTAGCTACAACGA CCCGTAGG 3315 1937 ACGGGAUG G CAUCAUCU 2370 AGATGATG GGCTAGCTACAACGA CATCCCGT 3316 1939 GGGAUGGC A UCAUCUCA 1579 TGAGATGA GGCTAGCTACAACGA GCCATCCC 3317 1942 AUGGCAUC A UCUCAGAU 1580 ATCTGAGA GGCTAGCTACAACGA GATGCCAT 3318 1949 CAUCUCAG A UAUAUUUG 2852 CAAATATA GGCTAGCTACAACGA CTGAGATG 3319 1951 UCUCAGAU A UAUUUGAU 406 ATCAAATA GGCTAGCTACAACGA ATCTGAGA 3320 1953 UCAGAUAU A UUUGAUAA 407 TTATCAAA GGCTAGCTACAACGA ATATCTGA 3321 1958 UAUAUUUG A UAAAAAAG 2853 CTTTTTTA GGCTAGCTACAACGA CAAATATA 3322 1972 AAGAAAAA A CUCUUCUA 2854 TAGAAGAG GGCTAGCTACAACGA TTTTTCTT 3323 1980 ACUCUUCU A CAGAAAUU 414 AATTTCTG GGCTAGCTACAACGA AGAAGAGT 3324 1986 CUACAGAA A UUACUCUC 2855 GAGAGTAA GGCTAGCTACAACGA TTCTGTAG 3325 1989 CAGAAAUU A CUCUCAAA 416 TTTGAGAG GGCTAGCTACAACGA AATTTCTG 3326 2001 UCAAAGAA A CCUGAGGA 2856 TCCTCAGG GGCTAGCTACAACGA TTCTTTGA 3327 2009 ACCUGAGG A UCGACCUA 2857 TAGGTCGA GGCTAGCTACAACGA CCTCAGGT 3328 2013 GAGGAUCG A CCUAACAC 2858 GTGTTAGG GGCTAGCTACAACGA CGATCCTC 3329 2018 UCGACCUA A CACAUCUG 2859 CAGATGTG GGCTAGCTACAACGA TAGGTCGA 3330 2020 GACCUAAC A CAUCUGAA 1594 TTCAGATG GGCTAGCTACAACGA GTTAGGTC 3331 2022 CCUAACAC A UCUGAAAU 1595 ATTTCAGA GGCTAGCTACAACGA GTGTTAGG 3332 2029 CAUCUGAA A UACUAAGG 2860 CCTTAGTA GGCTAGCTACAACGA TTCAGATG 3333 2031 UCUGAAAU A CUAAGGAC 422 GTCCTTAG GGCTAGCTACAACGA ATTTCAGA 3334 2038 UACUAAGG A CCUUGACU 2861 AGTCAAGG GGCTAGCTACAACGA CCTTAGTA 3335 2044 GGACCUUG A CUGUGUGG 2862 CCACACAG GGCTAGCTACAACGA CAAGGTCC 3336 2047 CCUUGACU G UGUGGAAG 2371 CTTCCACA GGCTAGCTACAACGA AGTCAAGG 3337 2049 UUGACUGU G UGGAAGAA 2372 TTCTTCCA GGCTAGCTACAACGA ACAGTCAA 3338 2060 GAAGAAAA G CCCAGAGA 2373 TCTCTGGG GGCTAGCTACAACGA TTTTCTTC 3339 2072 AGAGAAAA A UGAACGAC 2863 GTCGTTCA GGCTAGCTACAACGA TTTTCTCT 3340 2076 AAAAAUGA A CGACACAC 2864 GTGTGTCG GGCTAGCTACAACGA TCATTTTT 3341 2079 AAUGAACG A CACACAUG 2865 CATGTGTG GGCTAGCTACAACGA CGTTCATT 3342 2081 UGAACGAC A CACAUGUU 1604 AACATGTG GGCTAGCTACAACGA GTCGTTCA 3343 2083 AACGACAC A CAUGUUAG 1605 CTAACATG GGCTAGCTACAACGA GTGTCGTT 3344 2085 CGACACAC A UGUUAGAG 1606 CTCTAACA GGCTAGCTACAACGA GTGTGTCG 3345 2087 ACACACAU G UUAGAGCC 2374 GGCTCTAA GGCTAGCTACAACGA ATGTGTGT 3346 2093 AUGUUAGA G CCCUUCUG 2375 CAGAAGGG GGCTAGCTACAACGA TCTAACAT 3347 2107 CUGAAAAA G UAUCCUGC 2376 GCAGGATA GGCTAGCTACAACGA TTTTTCAG 3348 2109 GAAAAAGU A UCCUGCUU 429 AAGCAGGA GGCTAGCTACAACGA ACTTTTTC 3349 2114 AGUAUCCU G CUUCUGAU 2377 ATCAGAAG GGCTAGCTACAACGA AGGATACT 3350 2121 UGCUUCUG A UAUGCAGU 2866 ACTGCATA GGCTAGCTACAACGA CAGAAGCA 3351 2123 CUUCUGAU A UGCAGUUU 433 AAACTGCA GGCTAGCTACAACGA ATCAGAAG 3352 2125 UCUGAUAU G CAGUUUUC 2378 GAAAACTG GGCTAGCTACAACGA ATATCAGA 3353 2128 GAUAUGCA G UUUUCCUU 2379 AAGGAAAA GGCTAGCTACAACGA TGCATATC 3354 2139 UUCCUUAA A UUAUCUAA 2867 TTAGATAA GGCTAGCTACAACGA TTAAGGAA 3355 2142 CUUAAAUU A UCUAAAAU 441 ATTTTAGA GGCTAGCTACAACGA AATTTAAG 3356 2149 UAUCUAAA A UCUGCUAG 2868 CTAGCAGA GGCTAGCTACAACGA TTTAGATA 3357 2153 UAAAAUCU G CUAGGGAA 2380 TTCCCTAG GGCTAGCTACAACGA AGATTTTA 3358 2161 GCUAGGGA A UAUCAAUA 2869 TATTGATA GGCTAGCTACAACGA TCCCTAGC 3359 2163 UAGGGAAU A UCAAUAGA 446 TCTATTGA GGCTAGCTACAACGA ATTCCCTA 3360 2167 GAAUAUCA A UAGAUAUU 2870 AATATCTA GGCTAGCTACAACGA TGATATTC 3361 2171 AUCAAUAG A UAUUUACC 2871 GGTAAATA GGCTAGCTACAACGA CTATTGAT 3362 2173 CAAUAGAU A UUUACCUU 449 AAGGTAAA GGCTAGCTACAACGA ATCTATTG 3363 2177 AGAUAUUU A CCUUUUAU 452 ATAAAAGG GGCTAGCTACAACGA AAATATCT 3364 2184 UACCUUUU A UUUUAAUG 456 CATTAAAA GGCTAGCTACAACGA AAAAGGTA 3365 2190 UUAUUUUA A UGUUUCCU 2872 AGGAAACA GGCTAGCTACAACGA TAAAATAA 3366 2192 AUUUUAAU G UUUCCUUU 2381 AAAGGAAA GGCTAGCTACAACGA ATTAAAAT 3367 2202 UUCCUUUA A UUUUUUAC 2873 GTAAAAAA GGCTAGCTACAACGA TAAAGGAA 3368 2209 AAUUUUUU A CUAUUUUU 472 AAAAATAG GGCTAGCTACAACGA AAAAAATT 3369 2212 UUUUUACU A UUUUUACU 473 AGTAAAAA GGCTAGCTACAACGA AGTAAAAA 3370 2218 CUAUUUUU A CUAAUCUU 478 AAGATTAG GGCTAGCTACAACGA AAAAATAG 3371 2222 UUUUACUA A UCUUUCUG 2874 CAGAAAGA GGCTAGCTACAACGA TAGTAAAA 3372 2230 AUCUUUCU G CAGAAACA 2382 TGTTTCTG GGCTAGCTACAACGA AGAAAGAT 3373 2236 CUGCAGAA A CAGAAAGG 2875 CCTTTCTG GGCTAGCTACAACGA TTCTGCAG 3374 2244 ACAGAAAG G UUUUCUUC 2383 GAAGAAAA GGCTAGCTACAACGA CTTTCTGT 3375 2258 UUCUUUUU G CUUCAAAA 2384 TTTTGAAG GGCTAGCTACAACGA AAAAAGAA 3376 2267 CUUCAAAA A CAUUCUUA 2876 TAAGAATG GGCTAGCTACAACGA TTTTGAAG 3377 2269 UCAAAAAC A UUCUUACA 1636 TGTAAGAA GGCTAGCTACAACGA GTTTTTGA 3378 2275 ACAUUCUU A CAUUUUAC 499 GTAAAATG GGCTAGCTACAACGA AAGAATGT 3379 2277 AUUCUUAC A UUUUACUU 1638 AAGTAAAA GGCTAGCTACAACGA GTAAGAAT 3380 2282 UACAUUUU A CUUUUUCC 503 GGAAAAAG GGCTAGCTACAACGA AAAATGTA 3381 2293 UUUUCCUG G CUCAUCUC 2385 GAGATGAG GGCTAGCTACAACGA CAGGAAAA 3382 2297 CCUGGCUC A UCUCUUUA 1643 TAAAGAGA GGCTAGCTACAACGA GAGCCAGG 3383 2305 AUCUCUUU A UUCUUUUU 514 AAAAAGAA GGCTAGCTACAACGA AAAGAGAT 3384 2327 UUUUAAAG A CAGAGUCU 2877 AGACTCTG GGCTAGCTACAACGA CTTTAAAA 3385 2332 AAGACAGA G UCUCGCUC 2386 GAGCGAGA GGCTAGCTACAACGA TCTGTCTT 3386 2337 AGAGUCUC G CUCUGUUG 2387 CAACAGAG GGCTAGCTACAACGA GAGACTCT 3387 2342 CUCGCUCU G UUGCCCAG 2388 CTGGGCAA GGCTAGCTACAACGA AGAGCGAG 3388 2345 GCUCUGUU G CCCAGGCU 2389 AGCCTGGG GGCTAGCTACAACGA AACAGAGC 3389 2351 UUGCCCAG G CUGGAGUG 2390 CACTCCAG GGCTAGCTACAACGA CTGGGCAA 3390 2357 AGGCUGGA G UGCAAUGA 2391 TCATTGCA GGCTAGCTACAACGA TCCAGCCT 3391 2359 GCUGGAGU G CAAUGACA 2392 TGTCATTG GGCTAGCTACAACGA ACTCCAGC 3392 2362 GGAGUGCA A UGACACAG 2878 CTGTGTCA GGCTAGCTACAACGA TGCACTCC 3393 2365 GUGCAAUG A CACAGUCU 2879 AGACTGTG GGCTAGCTACAACGA CATTGCAC 3394 2367 GCAAUGAC A CAGUCUUG 1656 CAAGACTG GGCTAGCTACAACGA GTCATTGC 3395 2370 AUGACACA G UCUUGGCU 2393 AGCCAAGA GGCTAGCTACAACGA TGTGTCAT 3396 2376 CAGUCUUG G CUCACUGC 2394 GCAGTGAG GGCTAGCTACAACGA CAAGACTG 3397 2380 CUUGGCUC A CUGCAACU 1660 AGTTGCAG GGCTAGCTACAACGA GAGCCAAG 3398 2383 GGCUCACU G CAACUUCU 2395 AGAAGTTG GGCTAGCTACAACGA AGTGAGCC 3399 2386 UCACUGCA A CUUCUGCC 2880 GGCAGAAG GGCTAGCTACAACGA TGCAGTGA 3400

2392 CAACUUCU G CCUCUUGG 2396 CCAAGAGG GGCTAGCTACAACGA AGAAGTTG 3401 2401 CCUCUUGG G UUCAAGUG 2397 CACTTGAA GGCTAGCTACAACGA CCAAGAGG 3402 2407 GGGUUCAA G UGAUUCUC 2398 GAGAATCA GGCTAGCTACAACGA TTGAACCC 3403 2410 UUCAAGUG A UUCUCCUG 2881 CAGGAGAA GGCTAGCTACAACGA CACTTGAA 3404 2418 AUUCUCCU G CCUCAGCC 2399 GGCTGAGG GGCTAGCTACAACGA AGGAGAAT 3405 2424 CUGCCUCA G CCUCCUGA 2400 TCAGGAGG GGCTAGCTACAACGA TGAGGCAG 3406 2433 CCUCCUGA G UAGCUGGA 2401 TCCAGCTA GGCTAGCTACAACGA TCAGGAGG 3407 2436 CCUGAGUA G CUGGAUUA 2402 TAATCCAG GGCTAGCTACAACGA TACTCAGG 3408 2441 GUAGCUGG A UUACAGGC 2882 GCCTGTAA GGCTAGCTACAACGA CCAGCTAC 3409 2444 GCUGGAUU A CAGGCAUG 551 CATGCCTG GGCTAGCTACAACGA AATCCAGC 3410 2448 GAUUACAG G CAUGUGCC 2403 GGCACATG GGCTAGCTACAACGA CTGTAATC 3411 2450 UUACAGGC A UGUGCCAC 1681 GTGGCACA GGCTAGCTACAACGA GCCTGTAA 3412 2452 ACAGGCAU G UGCCACCC 2404 GGGTGGCA GGCTAGCTACAACGA ATGCCTGT 3413 2454 AGGCAUGU G CCACCCAC 2405 GTGGGTGG GGCTAGCTACAACGA ACATGCCT 3414 2457 CAUGUGCC A CCCACCCA 1683 TGGGTGGG GGCTAGCTACAACGA GGCACATG 3415 2461 UGCCACCC A CCCAACUA 1686 TAGTTGGG GGCTAGCTACAACGA GGGTGGCA 3416 2466 CCCACCCA A CUAAUUUU 2883 AAAATTAG GGCTAGCTACAACGA TGGGTGGG 3417 2470 CCCAACUA A UUUUUGUG 2884 CACAAAAA GGCTAGCTACAACGA TAGTTGGG 3418 2476 UAAUUUUU G UGUUUUUA 2406 TAAAAACA GGCTAGCTACAACGA AAAAATTA 3419 2478 AUUUUUGU G UUUUUAAU 2407 ATTAAAAA GGCTAGCTACAACGA ACAAAAAT 3420 2485 UGUUUUUA A UAAAGACA 2885 TGTCTTTA GGCTAGCTACAACGA TAAAAACA 3421 2491 UAAUAAAG A CAGGGUUU 2886 AAACCCTG GGCTAGCTACAACGA CTTTATTA 3422 2496 AAGACAGG G UUUCACCA 2408 TGGTGAAA GGCTAGCTACAACGA CCTGTCTT 3423 2501 AGGGUUUC A CCAUGUUG 1692 CAACATGG GGCTAGCTACAACGA GAAACCCT 3424 2504 GUUUCACC A UGUUGGCC 1694 GGCCAACA GGCTAGCTACAACGA GGTGAAAC 3425 2506 UUCACCAU G UUGGCCAG 2409 CTGGCCAA GGCTAGCTACAACGA ATGGTGAA 3426 2510 CCAUGUUG G CCAGGCUG 2410 CAGCCTGG GGCTAGCTACAACGA CAACATGG 3427 2515 UUGGCCAG G CUGGUCUC 2411 GAGACCAG GGCTAGCTACAACGA CTGGCCAA 3428 2519 CCAGGCUG G UCUCAAAC 2412 GTTTGAGA GGCTAGCTACAACGA CAGCCTGG 3429 2526 GGUCUCAA A CUCCUGAC 2887 GTCAGGAG GGCTAGCTACAACGA TTGAGACC 3430 2533 AACUCCUG A CCUCAAGU 2888 ACTTGAGG GGCTAGCTACAACGA CAGGAGTT 3431 2540 GACCUCAA G UAAUCCAC 2413 GTGGATTA GGCTAGCTACAACGA TTGAGGTC 3432 2543 CUCAAGUA A UCCACCUG 2889 CAGGTGGA GGCTAGCTACAACGA TACTTGAG 3433 2547 AGUAAUCC A CCUGCCUC 1707 GAGGCAGG GGCTAGCTACAACGA GGATTACT 3434 2551 AUCCACCU G CCUCGGCC 2414 GGCCGAGG GGCTAGCTACAACGA AGGTGGAT 3435 2557 CUGCCUCG G CCUCCCAA 2415 TTGGGAGG GGCTAGCTACAACGA CGAGGCAG 3436 2567 CUCCCAAA G UGCUGGGA 2416 TCCCAGCA GGCTAGCTACAACGA TTTGGGAG 3437 2569 CCCAAAGU G CUGGGAUU 2417 AATCCCAG GGCTAGCTACAACGA ACTTTGGG 3438 2575 GUGCUGGG A UUACAGGG 2890 CCCTGTAA GGCTAGCTACAACGA CCCAGCAC 3439 2578 CUGGGAUU A CAGGGAUG 576 CATCCCTG GGCTAGCTACAACGA AATCCCAG 3440 2584 UUACAGGG A UGAGCCAC 2891 GTGGCTCA GGCTAGCTACAACGA CCCTGTAA 3441 2588 AGGGAUGA G CCACCGCG 2418 CGCGGTGG GGCTAGCTACAACGA TCATCCCT 3442 2591 GAUGAGCC A CCGCGCCC 1720 GGGCGCGG GGCTAGCTACAACGA GGCTCATC 3443 2594 GAGCCACC G CGCCCAGC 2419 GCTGGGCG GGCTAGCTACAACGA GGTGGCTC 3444 2596 GCCACCGC G CCCAGCCU 2420 AGGCTGGG GGCTAGCTACAACGA GCGGTGGC 3445 2601 CGCGCCCA G CCUCAUCU 2421 AGATGAGG GGCTAGCTACAACGA TGGGCGCG 3446 2606 CCAGCCUC A UCUCUUUG 1727 CAAAGAGA GGCTAGCTACAACGA GAGGCTGG 3447 2614 AUCUCUUU G UUCUAAAG 2422 CTTTAGAA GGCTAGCTACAACGA AAAGAGAT 3448 2623 UUCUAAAG A UGGAAAAA 2892 TTTTTCCA GGCTAGCTACAACGA CTTTAGAA 3449 2631 AUGGAAAA A CCACCCCC 2893 GGGGGTGG GGCTAGCTACAACGA TTTTCCAT 3450 2634 GAAAAACC A CCCCCAAA 1732 TTTGGGGG GGCTAGCTACAACGA GGTTTTTC 3451 2642 ACCCCCAA A UUUUCUUU 2894 AAAGAAAA GGCTAGCTACAACGA TTGGGGGT 3452 2653 UUCUUUUU A UACUAUUA 593 TAATAGTA GGCTAGCTACAACGA AAAAAGAA 3453 2655 CUUUUUAU A CUAUUAAU 594 ATTAATAG GGCTAGCTACAACGA ATAAAAAG 3454 2658 UUUAUACU A UUAAUGAA 595 TTCATTAA GGCTAGCTACAACGA AGTATAAA 3455 2662 UACUAUUA A UGAAUCAA 2895 TTGATTCA GGCTAGCTACAACGA TAATAGTA 3456 2666 AUUAAUGA A UCAAUCAA 2896 TTGATTGA GGCTAGCTACAACGA TCATTAAT 3457 2670 AUGAAUCA A UCAAUUCA 2897 TGAATTGA GGCTAGCTACAACGA TGATTCAT 3458 2674 AUCAAUCA A UUCAUAUC 2898 GATATGAA GGCTAGCTACAACGA TGATTGAT 3459 2678 AUCAAUUC A UAUCUAUU 1742 AATAGATA GGCTAGCTACAACGA GAATTGAT 3460 2680 CAAUUCAU A UCUAUUUA 602 TAAATAGA GGCTAGCTACAACGA ATGAATTG 3461 2684 UCAUAUCU A UUUAUUAA 604 TTAATAAA GGCTAGCTACAACGA AGATATGA 3462 2688 AUCUAUUU A UUAAAUUU 607 AAATTTAA GGCTAGCTACAACGA AAATAGAT 3463 2693 UUUAUUAA A UUUCUACC 2899 GGTAGAAA GGCTAGCTACAACGA TTAATAAA 3464 2699 AAAUUUCU A CCGCUUUU 613 AAAAGCGG GGCTAGCTACAACGA AGAAATTT 3465 2702 UUUCUACC G CUUUUAGG 2423 CCTAAAAG GGCTAGCTACAACGA GGTAGAAA 3466 2710 GCUUUUAG G CCAAAAAA 2424 TTTTTTGG GGCTAGCTACAACGA CTAAAAGC 3467 2719 CCAAAAAA A UGUAAGAU 2900 ATCTTACA GGCTAGCTACAACGA TTTTTTGG 3468 2721 AAAAAAAU G UAAGAUCG 2425 CGATCTTA GGCTAGCTACAACGA ATTTTTTT 3469 2726 AAUGUAAG A UCGUUCUC 2901 GAGAACGA GGCTAGCTACAACGA CTTACATT 3470 2729 GUAAGAUC G UUCUCUGC 2426 GCAGAGAA GGCTAGCTACAACGA GATCTTAC 3471 2736 CGUUCUCU G CCUCACAU 2427 ATGTGAGG GGCTAGCTACAACGA AGAGAACG 3472 2741 UCUGCCUC A CAUAGCUU 1753 AAGCTATG GGCTAGCTACAACGA GAGGCAGA 3473 2743 UGCCUCAC A UAGCUUAC 1754 GTAAGCTA GGCTAGCTACAACGA GTGAGGCA 3474 2746 CUCACAUA G CUUACAAG 2428 CTTGTAAG GGCTAGCTACAACGA TATGTGAG 3475 2750 CAUAGCUU A CAAGCCAG 626 CTGGCTTG GGCTAGCTACAACGA AAGCTATG 3476 2754 GCUUACAA G CCAGCUGG 2429 CCAGCTGG GGCTAGCTACAACGA TTGTAAGC 3477 2758 ACAAGCCA G CUGGAGAA 2430 TTCTCCAG GGCTAGCTACAACGA TGGCTTGT 3478 2767 CUGGAGAA A UAUGGUAC 2902 GTACCATA GGCTAGCTACAACGA TTCTCCAG 3479 2769 GGAGAAAU A UGGUACUC 627 GAGTACCA GGCTAGCTACAACGA ATTTCTCC 3480 2772 GAAAUAUG G UACUCAUU 2431 AATGAGTA GGCTAGCTACAACGA CATATTTC 3481 2774 AAUAUGGU A CUCAUUAA 628 TTAATGAG GGCTAGCTACAACGA ACCATATT 3482 2778 UGGUACUC A UUAAAAAA 1761 TTTTTTAA GGCTAGCTACAACGA GAGTACCA 3483 2796 AAAAAAAA G UGAUGUAC 2432 GTACATCA GGCTAGCTACAACGA TTTTTTTT 3484 2799 AAAAAGUG A UGUACAAC 2903 GTTGTACA GGCTAGCTACAACGA CACTTTTT 3485 Input Sequence = NM_002759. Cut Site = R/Y Arm Length = 8. Core Sequence = GGCTAGCTACAACGA NM_002759 (Homo sapiens protein kinase, interferon-inducible double stranded RNA dependent (PRKR), mRNA.; 2808 bp)

[0274] TABLE-US-00012 TABLE XII Human PKR Amberzyme and Substrate Sequence Seq Seq Pos Substrate ID Amberzyme ID 9 GCGGCGGC G GCGGCGCA 3486 UGCGCCGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GCCGCCGC 3814 10 CGGCGGCG G CGGCGCAG 2261 CUGCGCCG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CGCCGCCG 3815 12 GCGGCGGC G GCGCAGUU 3487 AACUGCGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GCCGCCGC 3816 13 CGGCGGCG G CGCAGUUU 2433 AAACUGCG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CGCCGCCG 3817 15 GCGGCGGC G CAGUUUGC 2434 GCAAACUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GCCGCCGC 3818 18 GCGGCGCA G UUUGCUCA 2435 UGAGCAAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGCGCCGC 3819 22 CGCAGUUU G CUCAUACU 2436 AGUAUGAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAACUGCG 3820 33 CAUACUUU G UGACUUGC 2437 GCAAGUCA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAAGUAUG 3821 35 UACUUUGU G ACUUGCGG 3488 CCGCAAGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACAAAGUA 3822 40 UGUGACUU G CGGUCACA 2438 UGUGACCG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAGUCACA 3823 42 UGACUUGC G GUCACAGU 3489 ACUGUGAC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GCAAGUCA 3824 43 GACUUGCG G UCACAGUG 2439 CACUGUGA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CGCAAGUC 3825 49 CGGUCACA G UGGCAUUC 2440 GAAUGCCA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGUGACOG 3826 51 GUCACAGU G GCAUUCAG 3490 CUGAAUGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACUGUGAC 3827 52 UCACAGUG G CAUUCAGC 2441 GCUGAAUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CACUGUGA 3828 59 GGCAUUCA G CUCCACAC 2442 GUGUGGAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGAAUGCC 3829 70 CCACACUU G GUAGAACC 3491 GGUUCUAC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAGUGUGG 3830 71 CACACUUG G UAGAACCA 2443 UGGUUCUA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAAGUGUG 3831 74 ACUUGGUA G AACCACAG 3492 CUGUGGUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UACCAAGU 3832 82 GAACCACA G GCACGACA 3493 UGUCGUGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGUGGUUC 3833 83 AACCACAG G CACGACAA 2444 UUGUCGUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUGUGGUU 3834 87 ACAGGCAC G ACAAGCAU 3494 AUGCUUGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GUGCCUGU 3835 92 CACGACAA G CAUAGAAA 2445 UUUCUAUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUGUCGUG 3836 97 CAAGCAUA G AAACAUCC 3495 GGAUGUUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UAUGCUUG 3837 121 UCUUCAUC G AGGCAUCG 3496 CGAUGCCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GAUGAAGA 3838 123 UUCAUCGA G GCAUCGAG 3497 CUCGAUGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCGAUGAA 3839 124 UCAUCGAG G CAUCGAGG 2446 CCUCGAUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUCGAUGA 3840 129 GAGGCAUC G AGGUCCAU 3498 AUGGACCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GAUGCCUC 3841 131 GGCAUCGA G GUCCAUCC 3499 GGAUGGAC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCGAUGCC 3842 132 GCAUCGAG G UCCAUCCC 2447 OGGAUGGA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUCGAUGC 3843 152 AAAAAUCA G GAGACCCU 3500 AGGGUCUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGAUUUUU 3844 153 AAAAUCAG G AGACCCUG 3501 CAGGGUCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUGAUUUU 3845 155 AAUCAGGA G ACCCUGGC 3502 GCCAGGGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCCUGAUU 3846 161 GAGACCCU G GCUAUCAU 3503 AUGAUAGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGGGUCUC 3847 162 AGACCCUG G CUAUCAUA 2448 UAUGAUAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAGGGUCU 3848 171 CUAUCAUA G ACCUUAGU 3504 ACUAAGGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UAUGAUAG 3849 178 AGACCUUA G UCUUCGCU 2449 AGCGAAGA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UAAGGUCU 3850 184 UAGUCUUC G CUGGUAUA 2450 UAUACCAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GAAGACUA 3851 187 UCUUCGCU G GUAUACUC 3505 GAGUAUAC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGCGAAGA 3852 188 CUUCGCUG G UAUACUCG 2451 CGAGUAUA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAGCGAAG 3853 196 GUAUACUC G CUGUCUGU 2452 ACAGACAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GAGUAUAC 3854 199 UACUCGCU G UCUGUCAA 2453 UUGACAGA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGCGAGUA 3855 203 CGCUGUCU G UCAACCAG 2454 CUGGUUGA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGACAGCG 3856 211 GUCAACCA G CGGUUGAC 2455 GUCAACCG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGGUUGAC 3857 213 CAACCAGC G GUUGACUU 3506 AAGUCAAC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GCUGGUUG 3858 214 AACCAGCG G UUGACUUU 2456 AAAGUCAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CGCUGGUU 3859 217 CAGCGGUU G ACUUUUUU 3507 AAAAAAGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AACCGCUG 3860 229 UUUUUUAA G CCUUCUUU 2457 AAAGAAGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUAAAAAA 3861 252 UUUUACCA G UUUCUGGA 2458 UCCAGAAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGGUAAAA 3862 258 CAGUUUCU G GAGCAAAU 3508 AUUUGCUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGAAACUG 3863 259 AGUUUCUG G AGCAAAUU 3509 AAUUUGCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAGAAACU 3864 261 UUUCUGGA G CAAAUUCA 2459 UGAAUUUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCCAGAAA 3865 270 CAAAUUCA G UUUGCCUU 2460 AAGGCAAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGAAUUUG 3866 274 UUCAGUUU G CCUUCCUG 2461 CAGGAAGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAACUGAA 3867 282 GCCUUCCU G GAUUUGUA 3510 UACAAAUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGGAAGGC 3868 283 CCUUCCUG G AUUUGUAA 3511 UUACAAAU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAGGAAGG 3869 288 CUGGAUUU G UAAAUUGU 2462 ACAAUUUA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAAUCCAG 3870 295 UGUAAAUU G UAAUGACC 2463 GGUCAUUA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAUUUACA 3871 300 AUUGUAAU G ACCUCAAA 3512 UUUGAGGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUUACAAU 3872 315 AAACUUUA G CAGUUCUU 2464 AAGAACUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UAAAGUUU 3873 318 CUUUAGCA G UUCUUCCA 2465 UGGAAGAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGCUAAAG 3874 330 UUCCAUCU G ACUCAGGU 3513 ACCUGAGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGAUGGAA 3875 336 CUGACUCA G GUUUGCUU 3514 AAGCAAAC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGAGUCAG 3876 337 UGACUCAG G UUUGCUUC 2466 GAAGCAAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUGAGUCA 3877 341 UCAGGUUU G CUUCUCUG 2467 CAGAGAAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAACCUGA 3878 349 GCUUCUCU G GCGGUCUU 3515 AAGACCGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGAGAAGC 3879 350 CUUCUCUG G CGGUCUUC 2468 GAAGACCG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAGAGAAG 3880 352 UCUCUGGC G GUCUUCAG 3516 CUGAAGAC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GCCAGAGA 3881 353 CUCUGGCG G UCUUCAGA 2469 UCUGAAGA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CGCCAGAG 3882 360 GGUCUUCA G AAUCAACA 3517 UGUUGAUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGAAGACC 3883 380 ACACUUCC G UGAUUAUC 2470 GAUAAUCA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GGAAGUGU 3884 382 ACUUCCGU G AUUAUCUG 3518 CAGAUAAU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACGGAAGU 3885 390 GAUUAUCU G CGUGCAUU 2471 AAUGCACG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGAUAAUC 3886 392 UUAUCUGC G UGCAUUUU 2472 AAAAUGCA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GCAGAUAA 3887 394 AUCUGCGU G CAUUUUGG 2473 CCAAAAUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACGCAGAU 3888 401 UGCAUUUU G GACAAAGC 3519 GCUUUGUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAAAUGCA 3889 402 GCAUUUUG G ACAAAGCU 3520 AGCUUUGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAAAAUGC 3890 408 UGGACAAA G CUUCCAAC 2474 GUUGGAAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUUGUCCA 3891 419 UCCAACCA G GAUACGGG 3521 CCCGUAUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGGUUGGA 3892 420 CCAACCAG G AUACGGGA 3522 UCCCGUAU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUGGUUGG 3893 425 CAGGAUAC G GGAAGAAG 3523 CUUCUUCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GUAUCCUG 3894

426 AGGAUACG G GAAGAAGA 3524 UCUUCUUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CGUAUCCU 3895 427 GGAUACGG G AAGAAGAA 3525 UUCUUCUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCGUAUCC 3896 430 UACGGGAA G AAGAAAUG 3526 CAUUUCUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUCCCGUA 3897 433 GGGAAGAA G AAAUGGCU 3527 AGCCAUUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUCUUCCC 3898 438 GAAGAAAU G GCUGGUGA 3528 UCACCAGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUUUCUUC 3899 439 AAGAAAUG G CUGGUGAU 2475 AUCACCAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAUUUCUU 3900 442 AAAUGGCU G GUGAUCUU 3529 AAGAUCAC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGCCAUUU 3901 443 AAUGGCUG G UGAUCUUU 2476 AAAGAUCA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAGCCAUU 3902 445 UGGCUGGU G AUCUUUCA 3530 UGAAAGAU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACCAGCCA 3903 454 AUCUUUCA G CAGGUUUC 2477 GAAACCUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGAAAGAU 3904 457 UUUCAGCA G GUUUCUUC 3531 GAAGAAAC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGCUGAAA 3905 458 UUCAGCAG G UUUCUUCA 2478 UGAAGAAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUGCUGAA 3906 468 UUCUUCAU G GAGGAACU 3532 AGUUCCUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUGAAGAA 3907 469 UCUUCAUG G AGGAACUU 3533 AAGUUCCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAUGAAGA 3908 471 UUCAUGGA G GAACUUAA 3534 UUAAGUUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCCAUGAA 3909 472 UCAUGGAG G AACUUAAU 3535 AUUAAGUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUCCAUGA 3910 488 UACAUACC G UCAGAAGC 2479 GCUUCUGA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GGUAUGUA 3911 492 UACCGUCA G AAGCAGGG 3536 CCCUGCUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGACGGUA 3912 495 CGUCAGAA G CAGGGAGU 2262 ACUCCCUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUCUGACG 3913 498 CAGAAGCA G GGAGUAGU 3537 ACUACUCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGCUUCUG 3914 499 AGAAGCAG G GAGUAGUA 3538 UACUACUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUGCUUCU 3915 500 GAAGCAGG G AGUAGUAC 3539 GUACUACU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCUGCUUC 3916 502 AGCAGGGA G UAGUACUU 2263 AAGUACUA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCCCUGCU 3917 505 AGGGAGUA G UACUUAAA 2264 UUUAAGUA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UACUCCCU 3918 520 AAUAUCAA G AACUGCCU 3540 AGGCAGUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUGAUAUU 3919 525 CAAGAACU G CCUAAUUC 2265 GAAUUAGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGUUCUUG 3920 535 CUAAUUCA G GACCUCCA 3541 UGGAGGUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGAAUUAG 3921 536 UAAUUCAG G ACCUCCAC 3542 GUGGAGGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUGAAUUA 3922 547 CUCCACAU G AUAGGAGG 3543 CCUCCUAU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUGUGGAG 3923 551 ACAUGAUA G GAGGUUUA 3544 UAAACCUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UAUCAUGU 3924 552 CAUGAUAG G AGGUUUAC 3545 GUAAACCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUAUCAUG 3925 554 UGAUAGGA G GUUUACAU 3546 AUGUAAAC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCCUAUCA 3926 555 GAUAGGAG G UUUACAUU 2266 AAUGUAAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUCCUAUC 3927 568 CAUUUCAA G UUAUAAUA 2267 UAUUAUAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUGAAAUG 3928 577 UUAUAAUA G AUGGAAGA 3547 UCUUCCAU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UAUUAUAA 3929 580 UAAUAGAU G GAAGAGAA 3548 UUCUCUUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUCUAUUA 3930 581 AAUAGAUG G AAGAGAAU 3549 AUUCUCUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAUCUAUU 3931 584 AGAUGGAA G AGAAUUUC 3550 GAAAUUCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUCCAUCU 3932 586 AUGGAAGA G AAUUUCCA 3551 UGGAAAUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCUUCCAU 3933 595 AAUUUCCA G AAGGUGAA 3552 UUCACCUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGGAAAUU 3934 598 UUCCAGAA G GUGAAGGU 3553 ACCUUCAC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUCUGGAA 3935 599 UCCAGAAG G UGAAGGUA 2268 UACCUUCA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUUCUGGA 3936 601 CAGAAGGU G AAGGUAGA 3554 UCUACCUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACCUUCUG 3937 604 AAGGUGAA G GUAGAUCA 3555 UGAUCUAC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUCACCUU 3938 605 AGGUGAAG G UAGAUCAA 2269 UUGAUCUA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUUCACCU 3939 608 UGAAGGUA G AUCAAAGA 3556 UCUUUGAU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UACCUUCA 3940 615 AGAUCAAA G AAGGAAGC 3557 GCUUCCUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUUGAUCU 3941 618 UCAAAGAA G GAAGCAAA 3558 UUUGCUUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUCUUUGA 3942 619 CAAAGAAG G AAGCAAAA 3559 UUUUGCUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUUCUUUG 3943 622 AGAAGGAA G CAAAAAAU 2270 AUUUUUUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUCCUUCU 3944 631 CAAAAAAU G CCGCAGCC 2271 GGCUGCGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUUUUUUG 3945 634 AAAAUGCC G CAGCCAAA 2272 UUUGGCUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GGCAUUUU 3946 637 AUGCCGCA G CCAAAUUA 2273 UAAUUUGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGCGGCAU 3947 646 CCAAAUUA G CUGUUGAG 2274 CUCAACAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UAAUUUGG 3948 649 AAUUAGCU G UUGAGAUA 2275 UAUCUCAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGCUAAUU 3949 652 UAGCUGUU G AGAUACUU 3560 AAGUAUCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AACAGCUA 3950 654 GCUGUUGA G AUACUUAA 3561 UUAAGUAU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCAACAGC 3951 666 CUUAAUAA G GAAAAGAA 3562 UUCUUUUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUAUUAAG 3952 667 UUAAUAAG G AAAAGAAG 3563 CUUCUUUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUUAUUAA 3953 672 AAGGAAAA G AAGGCAGU 3564 ACUGCCUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUUUCCUU 3954 675 GAAAAGAA G GCAGUUAG 3565 CUAACUGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUCUUUUC 3955 676 AAAAGAAG G CAGUUAGU 2276 ACUAACUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUUCUUUU 3956 679 AGAAGGCA G UUAGUCCU 2277 AGGACUAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGCCUUCU 3957 683 GGCAGUUA G UCCUUUAU 2278 AUAAAGGA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UAACUGCC 3958 696 UUAUUAUU G ACAACAAC 3566 GUUGUUGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAUAAUAA 3959 705 ACAACAAC G AAUUCUUC 3567 GAAGAAUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GUUGUUGU 3960 715 AUUCUUCA G AAGGAUUA 3568 UAAUCCUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGAAGAAU 3961 718 CUUCAGAA G GAUUAUCC 3569 GGAUAAUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUCUGAAG 3962 719 UUCAGAAG G AUUAUCCA 3570 UGGAUAAU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUUCUGAA 3963 729 UUAUCCAU G GGGAAUUA 3571 UAAUUCCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUGGAUAA 3964 730 UAUCCAUG G GGAAUUAC 3572 GUAAUUCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAUGGAUA 3965 731 AUCCAUGG G GAAUUACA 3573 UGUAAUUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCAUGGAU 3966 732 UCCAUGGG G AAUUACAU 3574 AUGUAAUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCCAUGGA 3967 742 AUUACAUA G GCCUUAUC 3575 GAUAAGGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UAUGUAAU 3968 743 UUACAUAG G CCUUAUCA 2279 UGAUAAGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUAUGUAA 3969 755 UAUCAAUA G AAUUGCCC 3576 GGGCAAUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UAUUGAUA 3970 760 AUAGAAUU G CCCAGAAG 2280 CUUCUGGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAUUCUAU 3971 765 AUUGCCCA G AAGAAAAG 3577 CUUUUCUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGGGCAAU 3972 768 GCCCAGAA G AAAAGACU 3578 AGUCUUUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUCUGGGC 3973 773 GAAGAAAA G ACUAACUG 3579 CAGUUAGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUUUCUUC 3974 781 GACUAACU G UAAAUUAU 2281 AUAAUUUA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGUUAGUC 3975 790 UAAAUUAU G AACAGUGU 3580 ACACUGUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUAAUUUA 3976 795 UAUGAACA G UGUGCAUC 2282 GAUGCACA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGUUCAUA 3977 797 UGAACAGU G UGCAUCGG 2283 CCGAUGCA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACUGUUCA 3978

799 AACAGUGU G CAUCGGGG 2284 CCCCGAUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACACUGUU 3979 804 UGUGCAUC G GGGGUGCA 3581 UGCACCCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GAUGCACA 3980 805 GUGCAUCG G GGGUGCAU 3582 AUGCACCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CGAUGCAC 3981 806 UGCAUCGG G GGUGCAUG 3583 CAUGCACC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCGAUGCA 3982 807 GCAUCGGG G GUGCAUGG 3584 CCAUGCAC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCCGAUGC 3983 808 CAUCGGGG G UGCAUGGG 2285 CCCAUGCA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCCCGAUG 3984 810 UCGGGGGU G CAUGGGCC 2286 GGCCCAUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACCCCCGA 3985 814 GGGUGCAU G GGCCAGAA 3585 UUCUGGCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUGCACCC 3986 815 GGUGCAUG G GCCAGAAG 3586 CUUCUGGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAUGCACC 3987 816 GUGCAUGG G CCAGAAGG 2287 CCUUCUGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCAUGCAC 3988 820 AUGGGCCA G AAGGAUUU 3587 AAAUCCUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGGCCCAU 3989 823 GGCCAGAA G GAUUUCAU 3588 AUGAAAUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUCUGGCC 3990 824 GCCAGAAG G AUUUCAUU 3589 AAUGAAAU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUUCUGGC 3991 839 UUAUAAAU G CAAAAUGG 2288 CCAUUUUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUUUAUAA 3992 846 UGCAAAAU G GGACAGAA 3590 UUCUGUCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUUUUGCA 3993 847 GCAAAAUG G GACAGAAA 3591 UUUCUGUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAUUUUGC 3994 848 CAAAAUGG G ACAGAAAG 3592 CUUUCUGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCAUUUUG 3995 852 AUGGGACA G AAAGAAUA 3593 UAUUCUUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGUCCCAU 3996 856 GACAGAAA G AAUAUAGU 3594 ACUAUAUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUUCUGUC 3997 863 AGAAUAUA G UAUUGGUA 2289 UACCAAUA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UAUAUUCU 3998 868 AUAGUAUU G GUACAGGU 3595 ACCUGUAC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAUACUAU 3999 869 UAGUAUUG G UACAGGUU 2290 AACCUGUA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAAUACUA 4000 874 UUGGUACA G GUUCUACU 3596 AGUAGAAC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGUACCAA 4001 875 UGGUACAG G UUCUACUA 2291 UAGUAGAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUGUACCA 4002 888 ACUAAACA G GAAGCAAA 3597 UUUGCUUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGUUUAGU 4003 889 CUAAACAG G AAGCAAAA 3598 UUUUGCUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUGUUUAG 4004 892 AACAGGAA G CAAAACAA 2292 UUGUUUUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUCCUGUU 4005 903 AAACAAUU G GCCGCUAA 3599 UUAGCGGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAUUGUUU 4006 904 AACAAUUG G CCGCUAAA 2293 UUUAGCGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAAUUGUU 4007 907 AAUUGGCC G CUAAACUU 2294 AAGUUUAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GGCCAAUU 4008 916 CUAAACUU G CAUAUCUU 2295 AAGAUAUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAGUUUAG 4009 927 UAUCUUCA G AUAUUAUC 3600 GAUAAUAU GGAGGAAACUCC CU UCAAGGACAUCGUCCGOG UGAAGAUA 4010 937 UAUUAUCA G AAGAAACC 3601 GGUUUCUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGAUAAUA 4011 940 UAUCAGAA G AAACCUCA 3602 UGAGGUUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUCUGAUA 4012 949 AAACCUCA G UGAAAUCU 2296 AGAUUUCA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGAGGUUU 4013 951 ACCUCAGU G AAAUCUGA 3603 UCAGAUUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACUGAGGU 4014 958 UGAAAUCU G ACUACCUG 3604 CAGGUAGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGAUUUCA 4015 966 GACUACCU G UCCUCUGG 2297 CCAGAGGA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGGUAGUC 4016 973 UGUCCUCU G GUUCUUUU 3605 AAAAGAAC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGAGGACA 4017 974 GUCCUCUG G UUCUUUUG 2298 CAAAAGAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAGAGGAC 4018 982 GUUCUUUU G CUACUACG 2299 CGUAGUAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAAAGAAC 4019 990 GCUACUAC G UGUGAGUC 2300 GACUCACA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GUAGUAGC 4020 992 UACUACGU G UGAGUCCC 2301 GGGACUCA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACGUAGUA 4021 994 CUACGUGU G AGUCCCAA 3606 UUGGGACU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACACGUAG 4022 996 ACGUGUGA G UCCCAAAG 2302 CUUUGGGA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCACACGU 4023 1004 GUCCCAAA G CAACUCUU 2303 AAGAGUUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUUGGGAC 4024 1015 ACUCUUUA G UGACCAGC 2304 GCUGGUCA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UAAAGAGU 4025 1017 UCUUUAGU G ACCAGCAC 3607 GUGCUGGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACUAAAGA 4026 1022 AGUGACCA G CACACUCG 2305 CGAGUGUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGGUCACU 4027 1030 GCACACUC G CUUCUGAA 2306 UUCAGAAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GAGUGUGC 4028 1036 UCGCUUCU G AAUCAUCA 3608 UGAUGAUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGAAGCGA 4029 1048 CAUCAUCU G AAGGUGAC 3609 GUCACCUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGAUGAUG 4030 1051 CAUCUGAA G GUGACUUC 3610 GAAGUCAC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUCAGAUG 4031 1052 AUCUGAAG G UGACUUCU 2307 AGAAGUCA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUUCAGAU 4032 1054 CUGAAGGU G ACUUCUCA 3611 UGAGAAGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACCUUCAG 4033 1063 ACUUCUCA G CAGAUACA 2308 UGUAUCUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGAGAAGU 4034 1066 UCUCAGCA G AUACAUCA 3612 UGAUGUAU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGCUGAGA 4035 1075 AUACAUCA G AGAUAAAU 3613 AUUUAUCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGAUGUAU 4036 1077 ACAUCAGA G AUAAAUUC 3614 GAAUUUAU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCUGAUGU 4037 1091 UUCUAACA G UGACAGUU 2309 AACUGUCA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGUUAGAA 4038 1093 CUAACAGU G ACAGUUUA 3615 UAAACUGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACUGUUAG 4039 1097 CAGUGACA G UUUAAACA 2310 UGUUUAAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGUCACUG 4040 1106 UUUAAACA G UUCUUCGU 2311 ACGAAGAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGUUUAAA 4041 1113 AGUUCUUC G UUGCUUAU 2312 AUAAGCAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GAAGAACU 4042 1116 UCUUCGUU G CUUAUGAA 2313 UUCAUAAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AACGAAGA 4043 1122 UUGCUUAU G AAUGGUCU 3616 AGACCAUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUAAGCAA 4044 1126 UUAUGAAU G GUCUCAGA 3617 UCUGAGAC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUUCAUAA 4045 1127 UAUGAAUG G UCUCAGAA 2314 UUCUGAGA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAUUCAUA 4046 1133 UGGUCUCA G AAAUAAUC 3618 GAUUAUUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGAGACCA 4047 1145 UAAUCAAA G GAAGGCAA 3619 UUGCCUUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUUGAUUA 4048 1146 AAUCAAAG G AAGGCAAA 3620 UUUGCCUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUUUGAUU 4049 1149 CAAAGGAA G GCAAAAAG 3621 CUUUUUGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUCCUUUG 4050 1150 AAAGGAAG G CAAAAAGA 2315 UCUUUUUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUUCCUUU 4051 1157 GGCAAAAA G AUCUUUGG 3622 CCAAAGAU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUUUUGCC 4052 1164 AGAUCUUU G GCACCCAG 3623 CUGGGUGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAAGAUCU 4053 1165 GAUCUUUG G CACCCAGA 2316 UCUGGGUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAAAGAUC 4054 1172 GGCACCCA G AUUUGACC 3624 GGUCAAAU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGGGUGCC 4055 1177 CCAGAUUU G ACCUUCCU 3625 AGGAAGGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAAUCUGG 4056 1186 ACCUUCCU G ACAUGAAA 3626 UUUCAUGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGGAAGGU 4057 1191 CCUGACAU G AAAGAAAC 3627 GUUUCUUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUGUCAGG 4058 1195 ACAUGAAA G AAACAAAG 3628 CUUUGUUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUUCAUGU 4059 1203 GAAACAAA G UAUACUGU 2317 ACAGUAUA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUUGUUUC 4060 1210 AGUAUACU G UGGACAAG 2318 CUUGUCCA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGUAUACU 4061 1212 UAUACUGU G GACAAGAG 3629 CUCUUGUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG

ACAGUAUA 4062 1213 AUACUGUG G ACAAGAGG 3630 CCUCUUGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CACAGUAU 4063 1218 GUGGACAA G AGGUUUGG 3631 CCAAACCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUGUCCAC 4064 1220 GGACAAGA G GUUUGGCA 3632 UGCCAAAC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCUUGUCC 4065 1221 GACAAGAG G UUUGGCAU 2319 AUGCCAAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUCUUGUC 4066 1225 AGAGGUUU G GCAUGGAU 3633 AUCCAUGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAACCUCU 4067 1226 GAGGUUUG G CAUGGAUU 2320 AAUCCAUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAAACCUC 4068 1230 UUUGGCAU G GAUUUUAA 3634 UUAAAAUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUGCCAAA 4069 1231 UUGGCAUG G AUUUUAAA 3635 UUUAAAAU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAUGCCAA 4070 1240 AUUUUAAA G AAAUAGAA 3636 UUCUAUUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUUAAAAU 4071 1246 AAGAAAUA G AAUUAAUU 3637 AAUUAAUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UAUUUCUU 4072 1255 AAUUAAUU G GCUCAGGU 3638 ACCUGAGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAUUAAUU 4073 1256 AUUAAUUG G CUCAGGUG 2321 CACCUGAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAAUUAAU 4074 1261 UUGGCUCA G GUGGAUUU 3639 AAAUCCAC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGAGCCAA 4075 1262 UGGCUCAG G UGGAUUUG 2322 CAAAUCCA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUGAGCCA 4076 1264 GCUCAGGU G GAUUUGGC 3640 GCCAAAUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACCUGAGC 4077 1265 CUCAGGUG G AUUUGGCC 3641 GGCCAAAU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CACCUGAG 4078 1270 GUGGAUUU G GCCAAGUU 3642 AACUUGGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAAUCCAC 4079 1271 UGGAUUUG G CCAAGUUU 2323 AAACUUGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAAAUCCA 4080 1276 UUGGCCAA G UUUUCAAA 2324 UUUGAAAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUGGCCAA 4081 1285 UUUUCAAA G CAAAACAC 2325 GUGUUUUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUUGAAAA 4082 1295 AAAACACA G AAUUGACG 3643 CGUCAAUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGUGUUUU 4083 1300 ACAGAAUU G ACGGAAAG 3644 CUUUCCGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAUUCUGU 4084 1303 GAAUUGAC G GAAAGACU 3645 AGUCUUUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GUCAAUUC 4085 1304 AAUUGACG G AAAGACUU 3646 AAGUCUUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CGUCAAUU 4086 1308 GACGGAAA G ACUUACGU 3647 ACGUAAGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUUCCGUC 4087 1315 AGACUUAC G UUAUUAAA 2326 UUUAAUAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GUAAGUCU 4088 1325 UAUUAAAC G UGUUAAAU 2327 AUUUAACA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GUUUAAUA 4089 1327 UUAAACGU G UUAAAUAU 2328 AUAUUUAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACGUUUAA 4090 1342 AUAAUAAC G AGAAGGCG 3648 CGCCUUCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GUUAUUAU 4091 1344 AAUAACGA G AAGGCGGA 3649 UCCGCCUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCGUUAUU 4092 1347 AACGAGAA G GCGGAGCG 3650 CGCUCCGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUCUCGUU 4093 1348 ACGAGAAG G CGGAGCGU 2329 ACGCUCCG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUUCUCGU 4094 1350 GAGAAGGC G GAGCGUGA 3651 UCACGCUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GCCUUCUC 4095 1351 AGAAGGCG G AGCGUGAA 3652 UUCACGCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CGCCUUCU 4096 1353 AAGGCGGA G CGUGAAGU 2330 ACUUCACG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCCGCCUU 4097 1355 GGCGGAGC G UGAAGUAA 2331 UUACUUCA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GCUCCGCC 4098 1357 CGGAGCGU G AAGUAAAA 3653 UUUUACUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACGCUCCG 4099 1360 AGCGUGAA G UAAAAGCA 2332 UGCUUUUA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUCACGCU 4100 1366 AAGUAAAA G CAUUGGCA 2333 UGCCAAUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUUUACUU 4101 1371 AAAGCAUU G GCAAAACU 3654 AGUUUUGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAUGCUUU 4102 1372 AAGCAUUG G CAAAACUU 2334 AAGUUUUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAAUGCUU 4103 1381 CAAAACUU G AUCAUGUA 3655 UACAUGAU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAGUUUUG 4104 1387 UUGAUCAU G UAAAUAUU 2335 AAUAUUUA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUGAUCAA 4105 1396 UAAAUAUU G UUCACUAC 2336 GUAGUGAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAUAUUUA 4106 1408 ACUACAAU G GCUGUUGG 3656 CCAACAGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUUGUAGU 4107 1409 CUACAAUG G CUGUUGGG 2337 CCCAACAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAUUGUAG 4108 1412 CAAUGGCU G UUGGGAUG 2338 CAUCCCAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGCCAUUG 4109 1415 UGGCUGUU G GGAUGGAU 3657 AUCCAUCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AACAGCCA 4110 1416 GGCUGUUG G GAUGGAUU 3658 AAUCCAUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAACAGCC 4111 1417 GCUGUUGG G AUGGAUUU 3659 AAAUCCAU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCAACAGC 4112 1420 GUUGGGAU G GAUUUGAU 3660 AUCAAAUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUCCCAAC 4113 1421 UUGGGAUG G AUUUGAUU 3661 AAUCAAAU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAUCCCAA 4114 1426 AUGGAUUU G AUUAUGAU 3662 AUCAUAAU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAAUCCAU 4115 1432 UUGAUUAU G AUCCUGAG 3663 CUCAGGAU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUAAUCAA 4116 1438 AUGAUCCU G AGACCAGU 3664 ACUGGUCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGGAUCAU 4117 1440 GAUCCUGA G ACCAGUGA 3665 UCACUGGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCAGGAUC 4118 1445 UGAGACCA G UGAUGAUU 2339 AAUCAUCA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGGUCUCA 4119 1447 AGACCAGU G AUGAUUCU 3666 AGAAUCAU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACUGGUCU 4120 1450 CCAGUGAU G AUUCUCUU 3667 AAGAGAAU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUCACUGG 4121 1459 AUUCUCUU G AGAGCAGU 3668 ACUGCUCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAGAGAAU 4122 1461 UCUCUUGA G AGCAGUGA 3669 UCACUGCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCAAGAGA 4123 1463 UCUUGAGA G CAGUGAUU 2340 AAUCACUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCUCAAGA 4124 1466 UGAGAGCA G UGAUUAUG 2341 CAUAAUCA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGCUCUCA 4125 1468 AGAGCAGU G AUUAUGAU 3670 AUCAUAAU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACUGCUCU 4126 1474 GUGAUUAU G AUCCUGAG 3671 CUCAGGAU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUAAUCAC 4127 1480 AUGAUCCU G AGAACAGC 3672 GCUGUUCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGGAUCAU 4128 1482 GAUCCUGA G AACAGCAA 3673 UUGCUGUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCAGGAUC 4129 1487 UGAGAACA G CAAAAAUA 2342 UAUUUUUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGUUCUCA 4130 1496 CAAAAAUA G UUCAAGGU 2343 ACCUUGAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UAUUUUUG 4131 1502 UAGUUCAA G GUCAAAGA 3674 UCUUUGAC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUGAACUA 4132 1503 AGUUCAAG G UCAAAGAC 2344 GUCUUUGA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUUGAACU 4133 1509 AGGUCAAA G ACUAAGUG 3675 CACUUAGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUUGACCU 4134 1515 AAGACUAA G UGCCUUUU 2345 AAAAGGCA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUAGUCUU 4135 1517 GACUAAGU G CCUUUUCA 2346 UGAAAAGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACUUAGUC 4136 1533 AUCCAAAU G GAAUUCUG 3676 CAGAAUUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUUUGGAU 4137 1534 UCCAAAUG G AAUUCUGU 3677 ACAGAAUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAUUUGGA 4138 1541 GGAAUUCU G UGAUAAAG 2347 CUUUAUCA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGAAUUCC 4139 1543 AAUUCUGU G AUAAAGGG 3678 CCCUUUAU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACAGAAUU 4140 1549 GUGAUAAA G GGACCUUG 3679 CAAGGUCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUUAUCAC 4141 1550 UGAUAAAG G GACCUUGG 3680 CCAAGGUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUUUAUCA 4142 1551 GAUAAAGG G ACCUUGGA 3681 UCCAAGGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCUUUAUC 4143 1557 GGGACCUU G GAACAAUG 3682 CAUUGUUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAGGUCCC 4144 1558 GGACCUUG G AACAAUGG 3683 CCAUUGUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAAGGUCC 4145

1565 GGAACAAU G GAUUGAAA 3684 UUUCAAUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUUGUUCC 4146 1566 GAACAAUG G AUUGAAAA 3685 UUUUCAAU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAUUGUUC 4147 1570 AAUGGAUU G AAAAAAGA 3686 UCUUUUUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAUCCAUU 4148 1577 UGAAAAAA G AAGAGGCG 3687 CGCCUCUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUUUUUCA 4149 1580 AAAAAGAA G AGGCGAGA 3688 UCUCGCCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUCUUUUU 4150 1582 AAAGAAGA G GCGAGAAA 3689 UUUCUCGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCUUCUUU 4151 1583 AAGAAGAG G CGAGAAAC 2348 GUUUCUCG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUCUUCUU 4152 1585 GAAGAGGC G AGAAACUA 3690 UAGUUUCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GCCUCUUC 4153 1587 AGAGGCGA G AAACUAGA 3691 UCUAGUUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCGCCUCU 4154 1594 AGAAACUA G ACAAAGUU 3692 AACUUUGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UAGUUUCU 4155 1600 UAGACAAA G UUUUGGCU 2349 AGCCAAAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUUGUCUA 4156 1605 AAAGUUUU G GCUUUGGA 3693 UCCAAAGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAAACUUU 4157 1606 AAGUUUUG G CUUUGGAA 2350 UUCCAAAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAAAACUU 4158 1611 UUGGCUUU G GAACUCUU 3694 AAGAGUUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAAGCCAA 4159 1612 UGGCUUUG G AACUCUUU 3695 AAAGAGUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAAAGCCA 4160 1621 AACUCUUU G AACAAAUA 3696 UAUUUGUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAAGAGUU 4161 1636 UAACAAAA G GGGUGGAU 3697 AUCCACCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUUUGUUA 4162 1637 AACAAAAG G GGUGGAUU 3698 AAUCCACC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUUUUGUU 4163 1638 ACAAAAGG G GUGGAUUA 3699 UAAUCCAC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCUUUUGU 4164 1639 CAAAAGGG G UGGAUUAU 2351 AUAAUCCA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCCUUUUG 4165 1641 AAAGGGGU G GAUUAUAU 3700 AUAUAAUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACCCCUUU 4166 1642 AAGGGGUG G AUUAUAUA 3701 UAUAUAAU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CACCCCUU 4167 1673 AAUUCAUA G AGAUCUUA 3702 UAAGAUCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UAUGAAUU 4168 1675 UUCAUAGA G AUCUUAAG 3703 CUUAAGAU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCUAUGAA 4169 1683 GAUCUUAA G CCAAGUAA 2352 UUACUUGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUAAGAUC 4170 1688 UAAGCCAA G UAAUAUAU 2353 AUAUAUUA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUGGCUUA 4171 1702 UAUUCUUA G UAGAUACA 2354 UGUAUCUA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UAAGAAUA 4172 1705 UCUUAGUA G AUACAAAA 3704 UUUUGUAU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UACUAAGA 4173 1717 CAAAACAA G UAAAGAUU 2355 AAUCUUUA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUGUUUUG 4174 1722 CAAGUAAA G AUUGGAGA 3705 UCUCCAAU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUUACUUG 4175 1726 UAAAGAUU G GAGACUUU 3706 AAAGUCUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAUCUUUA 4176 1727 AAAGAUUG G AGACUUUG 3707 CAAAGUCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAAUCUUU 4177 1729 AGAUUGGA G ACUUUGGA 3708 UCCAAAGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCCAAUCU 4178 1735 GAGACUUU G GACUUGUA 3709 UACAAGUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAAGUCUC 4179 1736 AGACUUUG G ACUUGUAA 3710 UUACAAGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAAAGUCU 4180 1741 UUGGACUU G UAACAUCU 2356 AGAUGUUA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAGUCCAA 4181 1752 ACAUCUCU G AAAAAUGA 3711 UCAUUUUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGAGAUGU 4182 1759 UGAAAAAU G AUGGAAAG 3712 CUUUCCAU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUUUUUCA 4183 1762 AAAAUGAU G GAAAGCGA 3713 UCGCUUUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUCAUUUU 4184 1763 AAAUGAUG G AAAGCGAA 3714 UUCGCUUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAUCAUUU 4185 1767 GAUGGAAA G CGAACAAG 2357 CUUGUUCG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUUCCAUC 4186 1769 UGGAAAGC G AACAAGGA 3715 UCCUUGUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GCUUUCCA 4187 1775 GCGAACAA G GAGUAAGG 3716 CCUUACUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUGUUCGC 4188 1776 CGAACAAG G AGUAAGGG 3717 CCCUUACU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUUGUUCG 4189 1778 AACAAGGA G UAAGGGAA 2358 UUCCCUUA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCCUUGUU 4190 1782 AGGAGUAA G GGAACUUU 3718 AAAGUUCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUACUCCU 4191 1783 GGAGUAAG G GAACUUUG 3719 CAAAGUUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUUACUCC 4192 1784 GAGUAAGG G AACUUUGC 3720 GCAAAGUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCUUACUC 4193 1791 GGAACUUU G CGAUACAU 2359 AUGUAUCG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAAGUUCC 4194 1793 AACUUUGC G AUACAUGA 3721 UCAUGUAU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GCAAAGUU 4195 1800 CGAUACAU G AGCCCAGA 3722 UCUGGGCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUGUAUCG 4196 1802 AUACAUGA G CCCAGAAC 2360 GUUCUGGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCAUGUAU 4197 1807 UGAGCCCA G AACAGAUU 3723 AAUCUGUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGGGCUCA 4198 1812 CCAGAACA G AUUUCUUC 3724 GAAGAAAU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGUUCUGG 4199 1821 AUUUCUUC G CAAGACUA 2361 UAGUCUUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GAAGAAAU 4200 1825 CUUCGCAA G ACUAUGGA 3725 UCCAUAGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUGCGAAG 4201 1831 AAGACUAU G GAAAGGAA 3726 UUCCUUUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUAGUCUU 4202 1832 AGACUAUG G AAAGGAAG 3727 CUUCCUUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAUAGUCU 4203 1836 UAUGGAAA G GAAGUGGA 3728 UCCACUUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUUCCAUA 4204 1837 AUGGAAAG G AAGUGGAC 3729 GUCCACUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUUUCCAU 4205 1840 GAAAGGAA G UGGACCUC 2362 GAGGUCCA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUCCUUUC 4206 1842 AAGGAAGU G GACCUCUA 3730 UAGAGGUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACUUCCUU 4207 1843 AGGAAGUG G ACCUCUAC 3731 GUAGAGGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CACUUCCU 4208 1852 ACCUCUAC G CUUUGGGG 2363 CCCCAAAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GUAGAGGU 4209 1857 UACGCUUU G GGGCUAAU 3732 AUUAGCCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAAGCGUA 4210 1858 ACGCUUUG G GGCUAAUU 3733 AAUUAGCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAAAGCGU 4211 1859 CGCUUUGG G GCUAAUUC 3734 GAAUUAGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCAAAGCG 4212 1860 GCUUUGGG G CUAAUUCU 2364 AGAAUUAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCCAAAGC 4213 1870 UAAUUCUU G CUGAACUU 2365 AAGUUCAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAGAAUUA 4214 1873 UUCUUGCU G AACUUCUU 3735 AAGAAGUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGCAAGAA 4215 1885 UUCUUCAU G UAUGUGAC 2366 GUCACAUA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUGAAGAA 4216 1889 UCAUGUAU G UGACACUG 2367 CAGUGUCA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUACAUGA 4217 1891 AUGUAUGU G ACACUGCU 3736 AGCAGUGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACAUACAU 4218 1897 GUGACACU G CUUUUGAA 2368 UUCAAAAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGUGUCAC 4219 1903 CUGCUUUU G AAACAUCA 3737 UGAUGUUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAAAGCAG 4220 1914 ACAUCAAA G UUUUUCAC 2369 GUGAAAAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUUGAUGU 4221 1924 UUUUCACA G ACCUACGG 3738 CCGUAGGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGUGAAAA 4222 1931 AGACCUAC G GGAUGGCA 3739 UGCCAUCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GUAGGUCU 4223 1932 GACCUACG G GAUGGCAU 3740 AUGCCAUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CGUAGGUC 4224 1933 ACCUACGG G AUGGCAUC 3741 GAUGCCAU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCGUAGGU 4225 1936 UACGGGAU G GCAUCAUC 3742 GAUGAUGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUCCCGUA 4226 1937 ACGGGAUG G CAUCAUCU 2370 AGAUGAUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAUCCCGU 4227 1948 UCAUCUCA G AUAUAUUU 3743 AAAUAUAU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGAGAUGA 4228 1957 AUAUAUUU G AUAAAAAA 3744 UUUUUUAU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAAUAUAU 4229

1966 AUAAAAAA G AAAAAACU 3745 AGUUUUUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUUUUUAU 4230 1983 CUUCUACA G AAAUUACU 3746 AGUAAUUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGUAGAAG 4231 1998 CUCUCAAA G AAACCUGA 3747 UCAGGUUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUUGAGAG 4232 2005 AGAAACCU G AGGAUCGA 3748 UCGAUCCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGGUUUCU 4233 2007 AAACCUGA G GAUCGACC 3749 GGUCGAUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCAGGUUU 4234 2008 AACCUGAG G AUCGACCU 3750 AGGUCGAU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUCAGGUU 4235 2012 UGAGGAUC G ACCUAACA 3751 UGUUAGGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GAUCCUCA 4236 2026 ACACAUCU G AAAUACUA 3752 UAGUAUUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGAUGUGU 4237 2036 AAUACUAA G GACCUUGA 3753 UCAAGGUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUAGUAUU 4238 2037 AUACUAAG G ACCUUGAC 3754 GUCAAGGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUUAGUAU 4239 2043 AGGACCUU G ACUGUGUG 3755 CACACAGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAGGUCCU 4240 2047 CCUUGACU G UGUGGAAG 2371 CUUCCACA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGUCAAGG 4241 2049 UUGACUGU G UGGAAGAA 2372 UUCUUCCA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACAGUCAA 4242 2051 GACUGUGU G GAAGAAAA 3756 UUUUCUUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACACAGUC 4243 2052 ACUGUGUG G AAGAAAAG 3757 CUUUUCUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CACACAGU 4244 2055 GUGUGGAA G AAAAGCCC 3758 GGGCUUUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUCCACAC 4245 2060 GAAGAAAA G CCCAGAGA 2373 UCUCUGGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUUUCUUC 4246 2065 AAAGCCCA G AGAAAAAU 3759 AUUUUUCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGGGCUUU 4247 2067 AGCCCAGA G AAAAAUGA 3760 UCAUUUUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCUGGGCU 4248 2074 AGAAAAAU G AACGACAC 3761 GUGUCGUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUUUUUCU 4249 2078 AAAUGAAC G ACACACAU 3762 AUGUGUGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GUUCAUUU 4250 2087 ACACACAU G UUAGAGCC 2374 GGCUCUAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUGUGUGU 4251 2091 ACAUGUUA G AGCCCUUC 3763 GAAGGGCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UAACAUGU 4252 2093 AUGUUAGA G CCCUUCUG 2375 CAGAAGGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCUAACAU 4253 2101 GCCCUUCU G AAAAAGUA 3764 UACUUUUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGAAGGGC 4254 2107 CUGAAAAA G UAUCCUGC 2376 GCAGGAUA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUUUUCAG 4255 2114 AGUAUCCU G CUUCUGAU 2377 AUCAGAAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGGAUACU 4256 2120 CUGCUUCU G AUAUGCAG 3765 CUGCAUAU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGAAGCAG 4257 2125 UCUGAUAU G CAGUUUUC 2378 GAAAACUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUAUCAGA 4258 2128 GAUAUGCA G UUUUCCUU 2379 AAGGAAAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGCAUAUC 4259 2153 UAAAAUCU G CUAGGGAA 2380 UUCCCUAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGAUUUUA 4260 2157 AUCUGCUA G GGAAUAUC 3766 GAUAUUCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UAGCAGAU 4261 2158 UCUGCUAG G GAAUAUCA 3767 UGAUAUUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUAGCAGA 4262 2159 CUGCUAGG G AAUAUCAA 3768 UUGAUAUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCUAGCAG 4263 2170 UAUCAAUA G AUAUUUAC 3769 GUAAAUAU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UAUUGAUA 4264 2192 AUUUUAAU G UUUCCUUU 2381 AAAGGAAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUUAAAAU 4265 2230 AUCUUUCU G CAGAAACA 2382 UGUUUCUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGAAAGAU 4266 2233 UUUCUGCA G AAACAGAA 3770 UUCUGUUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGCAGAAA 4267 2239 CAGAAACA G AAAGGUUU 3771 AAACCUUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGUUUCUG 4268 2243 AACAGAAA G GUUUUCUU 3772 AAGAAAAC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUUCUGUU 4269 2244 ACAGAAAG G UUUUCUUC 2383 GAAGAAAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUUUCUGU 4270 2258 UUCUUUUU G CUUCAAAA 2384 UUUUGAAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAAAAGAA 4271 2292 UUUUUCCU G GCUCAUCU 3773 AGAUGAGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGGAAAAA 4272 2293 UUUUCCUG G CUCAUCUC 2385 GAGAUGAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAGGAAAA 4273 2326 UUUUUAAA G ACAGAGUC 3774 GACUCUGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUUAAAAA 4274 2330 UAAAGACA G AGUCUCGC 3775 GCGAGACU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGUCUUUA 4275 2332 AAGACAGA G UCUCGCUC 2386 GAGCGAGA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCUGUCUU 4276 2337 AGAGUCUC G CUCUGUUG 2387 CAACAGAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GAGACUCU 4277 2342 CUCGCUCU G UUGCCCAG 2388 CUGGGCAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGAGCGAG 4278 2345 GCUCUGUU G CCCAGGCU 2389 AGCCUGGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AACAGAGC 4279 2350 GUUGCCCA G GCUGGAGU 3776 ACUCCAGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGGGCAAC 4280 2351 UUGCCCAG G CUGGAGUG 2390 CACUCCAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUGGGCAA 4281 2354 CCCAGGCU G GAGUGCAA 3777 UUGCACUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGCCUGGG 4282 2355 CCAGGCUG G AGUGCAAU 3778 AUUGCACU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAGCCUGG 4283 2357 AGGCUGGA G UGCAAUGA 2391 UCAUUGCA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCCAGCCU 4284 2359 GCUGGAGU G CAAUGACA 2392 UGUCAUUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACUCCAGC 4285 2364 AGUGCAAU G ACACAGUC 3779 GACUGUGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUUGCACU 4286 2370 AUGACACA G UCUUGGCU 2393 AGCCAAGA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGUGUCAU 4287 2375 ACAGUCUU G GCUCACUG 3780 CAGUGAGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAGACUGU 4288 2376 CAGUCUUG G CUCACUGC 2394 GCAGUGAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAAGACUG 4289 2383 GGCUCACU G CAACUUCU 2395 AGAAGUUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGUGAGCC 4290 2392 CAACUUCU G CCUCUUGG 2396 CCAAGAGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGAAGUUG 4291 2399 UGCCUCUU G GGUUCAAG 3781 CUUGAACC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAGAGGCA 4292 2400 GCCUCUUG G GUUCAAGU 3782 ACUUGAAC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAAGAGGC 4293 2401 CCUCUUGG G UUCAAGUG 2397 CACUUGAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCAAGAGG 4294 2407 GGGUUCAA G UGAUUCUC 2398 GAGAAUCA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUGAACCC 4295 2409 GUUCAAGU G AUUCUCCU 3783 AGGAGAAU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACUUGAAC 4296 2418 AUUCUCCU G CCUCAGCC 2399 GGCUGAGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGGAGAAU 4297 2424 CUGCCUCA G CCUCCUGA 2400 UCAGGAGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGAGGCAG 4298 2431 AGCCUCCU G AGUAGCUG 3784 CAGCUACU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGGAGGCU 4299 2433 CCUCCUGA G UAGCUGGA 2401 UCCAGCUA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCAGGAGG 4300 2436 CCUGAGUA G CUGGAUUA 2402 UAAUCCAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UACUCAGG 4301 2439 GAGUAGCU G GAUUACAG 3785 CUGUAAUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGCUACUC 4302 2440 AGUAGCUG G AUUACAGG 3786 CCUGUAAU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAGCUACU 4303 2447 GGAUUACA G GCAUGUGC 3787 GCACAUGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGUAAUCC 4304 2448 GAUUACAG G CAUGUGCC 2403 GGCACAUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUGUAAUC 4305 2452 ACAGGCAU G UGCCACCC 2404 GGGUGGCA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUGCCUGU 4306 2454 AGGCAUGU G CCACCCAC 2405 GUGGGUGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACAUGCCU 4307 2476 UAAUUUUU G UGUUUUUA 2406 UAAAAACA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAAAAUUA 4308 2478 AUUUUUGU G UUUUUAAU 2407 AUUAAAAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACAAAAAU 4309 2490 UUAAUAAA G ACAGGGUU 3788 AACCCUGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUUAUUAA 4310 2494 UAAAGACA G GGUUUCAC 3789 GUGAAACC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGUCUUUA 4311 2495 AAAGACAG G GUUUCACC 3790 GGUGAAAC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUGUCUUU 4312 2496 AAGACAGG G UUUCACCA 2408 UGGUGAAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG

CCUGUCUU 4313 2506 UUCACCAU G UUGGCCAG 2409 CUGGCCAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUGGUGAA 4314 2509 ACCAUGUU G GCCAGGCU 3791 AGCCUGGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AACAUGGU 4315 2510 CCAUGUUG G CCAGGCUG 2410 CAGCCUGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAACAUGG 4316 2514 GUUGGCCA G GCUGGUCU 3792 AGACCAGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGGCCAAC 4317 2515 UUGGCCAG G CUGGUCUC 2411 GAGACCAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUGGCCAA 4318 2518 GCCAGGCU G GUCUCAAA 3793 UUUGAGAC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGCCUGGC 4319 2519 CCAGGCUG G UCUCAAAC 2412 GUUUGAGA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAGCCUGG 4320 2532 AAACUCCU G ACCUCAAG 3794 CUUGAGGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGGAGUUU 4321 2540 GACCUCAA G UAAUCCAC 2413 GUGGAUUA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUGAGGUC 4322 2551 AUCCACCU G CCUCGGCC 2414 GGCCGAGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGGUGGAU 4323 2556 CCUGCCUC G GCCUCCCA 3795 UGGGAGGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GAGGCAGG 4324 2557 CUGCCUCG G CCUCCCAA 2415 UUGGGAGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CGAGGCAG 4325 2567 CUCCCAAA G UGCUGGGA 2416 UCCCAGCA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUUGGGAG 4326 2569 CCCAAAGU G CUGGGAUU 2417 AAUCCCAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACUUUGGG 4327 2572 AAAGUGCU G GGAUUACA 3796 UGUAAUCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGCACUUU 4328 2573 AAGUGCUG G GAUUACAG 3797 CUGUAAUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAGCACUU 4329 2574 AGUGCUGG G AUUACAGG 3798 CCUGUAAU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCAGCACU 4330 2581 GGAUUACA G GGAUGAGC 3799 GCUCAUCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGUAAUCC 4331 2582 GAUUACAG G GAUGAGCC 3800 GGCUCAUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUGUAAUC 4332 2583 AUUACAGG G AUGAGCCA 3801 UGGCUCAU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCUGUAAU 4333 2586 ACAGGGAU G AGCCACCG 3802 CGGUGGCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUCCCUGU 4334 2588 AGGGAUGA G CCACCGCG 2418 CGCGGUGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCAUCCCU 4335 2594 GAGCCACC G CGCCCAGC 2419 GCUGGGCG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GGUGGCUC 4336 2596 GCCACCGC G CCCAGCCU 2420 AGGCUGGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GCGGUGGC 4337 2601 CGCGCCCA G CCUCAUCU 2421 AGAUGAGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGGGCGCG 4338 2614 AUCUCUUU G UUCUAAAG 2422 CUUUAGAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAAGAGAU 4339 2622 GUUCUAAA G AUGGAAAA 3803 UUUUCCAU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUUAGAAC 4340 2625 CUAAAGAU G GAAAAACC 3804 GGUUUUUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUCUUUAG 4341 2626 UAAAGAUG G AAAAACCA 3805 UGGUUUUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAUCUUUA 4342 2664 CUAUUAAU G AAUCAAUC 3806 GAUUGAUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUUAAUAG 4343 2702 UUUCUACC G CUUUUAGG 2423 CCUAAAAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GGUAGAAA 4344 2709 CGCUUUUA G GCCAAAAA 3807 UUUUUGGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UAAAAGCG 4345 2710 GCUUUUAG G CCAAAAAA 2424 UUUUUUGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUAAAAGC 4346 2721 AAAAAAAU G UAAGAUCG 2425 CGAUCUUA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUUUUUUU 4347 2725 AAAUGUAA G AUCGUUCU 3808 AGAACGAU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUACAUUU 4348 2729 GUAAGAUC G UUCUCUGC 2426 GCAGAGAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GAUCUUAC 4349 2736 CGUUCUCU G CCUCACAU 2427 AUGUGAGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGAGAACG 4350 2746 CUCACAUA G CUUACAAG 2428 CUUGUAAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UAUGUGAG 4351 2754 GCUUACAA G CCAGCUGG 2429 CCAGCUGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUGUAAGC 4352 2758 ACAAGCCA G CUGGAGAA 2430 UUCUCCAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGGCUUGU 4353 2761 AGCCAGCU G GAGAAAUA 3809 UAUUUCUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGCUGGCU 4354 2762 GCCAGCUG G AGAAAUAU 3810 AUAUUUCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAGCUGGC 4355 2764 CAGCUGGA G AAAUAUGG 3811 CCAUAUUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCCAGCUG 4356 2771 AGAAAUAU G GUACUCAU 3812 AUGAGUAC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUAUUUCU 4357 2772 GAAAUAUG G UACUCAUU 2431 AAUGAGUA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAUAUUUC 4358 2796 AAAAAAAA G UGAUGUAC 2432 GUACAUCA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUUUUUUU 4359 2798 AAAAAAGU G AUGUACAA 3813 UUGUACAU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACUUUUUU 4360 Input Sequence = NM_002759. Cut Site = G/. Arm Length = 8. Core Sequence = GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG NM_002759 (Homo sapiens protein kinase, interferon-inducible double stranded RNA dependent (PRKR), mRNA.; 2808 bp)

[0275] TABLE-US-00013 TABLE XIII Human IKK-gamma and PKR Nucleic Acid and Target molecules Seq Gene Pos Target Seq ID RPI# Enzymatic Nucleic Acid ID PKR 563 UUUACAUUUCAAGUU 7771 24072 a.sub.Sa.sub.Sc.sub.Su.sub.SugacUGAuGaggccguuaggccGaaAuguaaaB 7884 PKR 571 UCAAGUUAUAAUAGA 7772 24073 u.sub.Sc.sub.Su.sub.Sa.sub.SuuacUGAuGaggccguuaggccGaaAacuugaB 7885 PKR 644 GCCAAAUUAGCUGUU 7773 24074 a.sub.Sa.sub.Sc.sub.Sa.sub.SgcucUGAuGaggccguuaggccGaaAuuuggcB 7886 PKR 645 CCAAAUUAGCUGUUG 7774 24075 c.sub.Sa.sub.Sa.sub.Sc.sub.SagccUGAuGaggccguuaggccGaaAauuuggB 7887 PKR 1259 UUGGCUCAGGUGG 7775 24076 c.sub.Sc.sub.Sa.sub.Sc.sub.ScucUGAuGaggccguuaggccGaaAgccaaB 7888 PKR 1259 AUUGGCUCAGGUGGA 7776 24077 u.sub.Sc.sub.Sc.sub.Sa.sub.SccucUGAuGaggccguuaggccGaaAgccaauB 7889 PKR 1538 UGGAAUUCUGUGA 7777 24078 u.sub.Sc.sub.Sa.sub.Sc.sub.SagcUGAuGaggccguuaggccGaaAuuccaB 7890 PKR 1538 AUGGAAUUCUGUGAU 7778 24079 a.sub.Su.sub.Sc.sub.Sa.sub.ScagcUGAuGaggccguuaggccGaaAuuccauB 7891 PKR 1678 AGAGAUCUUAAGC 7779 24080 g.sub.Sc.sub.Su.sub.Su.sub.SaacUGAuGaggccguuaggccGaaAucucuB 7892 PKR control GACGAUUGCAAUC 7780 24081 g.sub.Sa.sub.Su.sub.Su.sub.SgccUAGuGacgccguuaggcgGaaAucgucB 7893 PKR control ACACCGUUGGAUCGC 7781 24082 g.sub.Sc.sub.Sg.sub.Sa.sub.SucccUAGuGaggccguuaggccGaalcgguguB 7894 PKR 764 UUGCCCAGAAGAA 7782 24153 u.sub.Su.sub.Sc.sub.Su.sub.SuccUGAuGaggccguuaggccGaalggcaaB 7895 PKR 1540 GGAAUUCUGUGAUAA 7783 24154 u.sub.Su.sub.Sa.sub.Su.sub.ScaccUGAuGaggccguuaggccGaalaauuccB 7896 PKR 1679 GAGAUCUUAAGCC 7784 24155 g.sub.Sg.sub.Sc.sub.Su.sub.SuacUGAuGaggccguuaggccGaalaucucB 7897 PKR 1679 AGAGAUCUUAAGCCA 7785 24156 u.sub.Sg.sub.Sg.sub.Sc.sub.SuuacUGAuGaggccguuaggccGaalaucucuB 7898 PKR Control ACUGGCAUACAUG 7786 24157 c.sub.Sa.sub.Su.sub.Sg.sub.SuacUAGuGacgccguuaggcgGaaIccaguB 7899 PKR Control CAUUCGCUAAAUGAG 7787 24158 c.sub.Su.sub.Sc.sub.Sa.sub.SuuucUAGuGacgccguuaggcgGaalcgaaugB 7900 PKR 1348 GAGAAGGCGGAGC 7788 24210 g.sub.Sc.sub.Su.sub.Sc.sub.ScggccgaaaggCgagugaGguCucuucucB 7901 PKR Control CCGUACGUUAAGA 7789 24211 u.sub.Sc.sub.Su.sub.Su.sub.SaagccgaaaggCuCugGagugagguacggB 7902 PKR Control ACGAAGAGUUACCUU 7790 24212 a.sub.Sa.sub.Sg.sub.Sg.sub.SuaagccgaaaggCuCugGagugagucuucguB 7903 PKR 1224 AGAGGUUUGGCAUGG 7791 24416 ccaugccCUGAUGAggccguuaggccGAAAaccucuB 7904 PKR 1556 GGGACCUUGGAACAA 7792 24417 uuguuccCUGAUGAggccguuaggccGAAAggucccB 7905 PKR 1780 AAGGAGUAAGGGAAC 7793 24418 guucccuCUGAUGAggccguuaggccGAAAcuccuuB 7906 PKR 2296 CCUGGCUCAUCUCUU 7794 24419 aagagauCUGAUGAggccguuaggccGAAAgccaggB 7907 PKR 2732 GAUCGUUCUCUGCCU 7795 24420 aggcagaCUGAUGAggccguuaggccGAAAacgaucB 7908 PKR 198 UACUCGCUGUCUGUC 7796 24421 gacagacCUGAUGAggccguuaggccGAAlcgaguaB 7909 PKR 322 GCAGUUCUUCCAUCU 7797 24422 agauggaCUGAUGAggccguuaggccGAAlaacugcB 7910 PKR 1805 AUGAGCCCAGAACAG 7798 24423 cuguucuCUGAUGAggccguuaggccGAAlgcucauB 7911 PKR 2297 CUGGCUCAUCUCUUU 7799 24424 aaagagaCUGAUGAggccguuaggccGAAlagccagB 7912 PKR 2733 AUCGUUCUCUGCCUC 7800 24425 gaggcagCUGAUGAggccguuaggccGAAlaacgauB 7913 PKR 199 ACUCGCUGUCUGUCA 7801 24426 ugacagagccgaaaggCgagugaGGuCuagcgaguB 7914 PKR 810 CGGGGGUGCAUGGGC 7802 24427 gcccauggccgaaaggCgagugaGGuCuacccccgB 7915 PKR 904 ACAAUUGGCCGCUAA 7803 24428 uuagcgggccgaaaggCgagugaGGuCucaauuguB 7916 PKR 966 ACUACCUGUCCUCUG 7804 24429 cagaggagccgaaaggCgagugaGGuCuagguaguB 7917 PKR 992 ACUACGUGUGAGUCC 7805 24430 ggacucagccgaaaggCgagugaGGuCuacguaguB 7918 PKR 396 UGCGUGCAUUUUGGA 7806 24431 uccaaaaGGCTAGCTACAACGAgcacgcaB 7919 PKR 966 ACUACCUGUCCUCUG 7804 24432 cagaggaGGCTAGCTACAACGAagguaguB 7920 PKR 1563 UGGAACAAUGGAUUG 7807 24433 caauccaGGCTAGCTACAACGAuguuccaB 7921 PKR 2297 CUGGCUCAUCUCUUU 7799 24434 aaagagaGGCTAGCTACAACGAgagccagB 7922 PKR 2543 UCAAGUAAUCCACCU 7808 24435 agguggaGGCTAGCTACAACGAuacuugaB 7923 PKR 604 AGGUGAAGGUAGAUC 7809 24436 gaucuacGgaggaaacucCCUUCaaggacaucgucCGGGuucaccuB 7924 PKR 903 AACAAUUGGCCGCUA 7810 24437 uagcggcGgaggaaacucCCUUCaaggacaucgucCGGGaauuguuB 7925 PKR 966 ACUACCUGUCCUCUG 7804 24438 cagaggaGgaggaaacucCCUUCaaggacaucgucCGGGagguaguB 7926 PKR 1186 CCUUCCUGACAUGAA 7811 24439 uucauguGgaggaaacucCCUUCaaggacaucgucCGGGaggaaggB 7927 PKR 2292 UUUUCCUGGCUCAUC 7812 24440 gaugagcGgaggaaacucCCUUCaaggacaucgucCGGGaggaaaaB 7928 IKKg 427 AGUUCCUCAUGUGCA 7813 24083 u.sub.Sg.sub.Sc.sub.Sa.sub.ScaucUGAuGaggccguuaggccGaaAggaacuB 7929 IKKg 1067 GCGGAUAUCUACA 7814 24084 u.sub.Sg.sub.Su.sub.Sa.sub.SgacUGAuGaggccguuaggccGaaAuccgcB 7930 IKKg 1067 GGCGGAUAUCUACAA 7815 24085 u.sub.Su.sub.Sg.sub.Su.sub.SagacUGAuGaggccguuaggccGaaAuccgccB 7931 IKKg 1069 CGGAUAUCUACAAGG 7816 24086 c.sub.Sc.sub.Su.sub.Su.sub.SguacUGAuGaggccguuaggccGaaAuauccgB 7932 IKKg 1071 AUAUCUACAAGGC 7817 24087 g.sub.Sc.sub.Sc.sub.Su.sub.SugcUGAuGaggccguuaggccGaaAgauauB 7933 IKKg 1390 UACAUGUCAUGGAGU 7818 24088 a.sub.Sc.sub.Su.sub.Sc.sub.ScaucUGAuGaggccguuaggccGaaAcauguaB 7934 IKKg 1402 AGUGCAUUGAGUAGG 7819 24089 c.sub.Sc.sub.Su.sub.Sa.sub.ScuccUGAuGaggccguuaggccGaaAugcacuB 7935 IKKg control ACGACUCGGAGCU 7820 24090 a.sub.Sg.sub.Sc.sub.Su.sub.ScccUAGuGacgccguuaggcgGaaAgucguB 7936 IKKg control UCUGAGUCAGGCGAC 7821 24091 g.sub.Su.sub.Sc.sub.Sg.sub.SccucUAGuGacgccguuaggcgGaaAcucagaB 7937 IKKg 195 UGCAGCCCAGUGG 7822 24159 c.sub.Sc.sub.Sa.sub.Sc.sub.SugcUGAuGaggccguuaggccGaalcugcaB 7938 IKKg 196 GCAGCCCAGUGGU 7823 24160 a.sub.Sc.sub.Sc.sub.Sa.sub.ScucUGAuGaggccguuaggccGaalgcugcB 7939 IKKg 303 CCCUCCAGCGCUG 7824 24161 c.sub.Sa.sub.Sg.sub.Sc.sub.SgccUGAuGaggccguuaggccGaalgagggB 7940 IKKg 324 AGAAUCAAGAGCU 7825 24162 a.sub.Sg.sub.Sc.sub.Su.sub.ScucUGAuGaggccguuaggccGaalauucuB 7941 IKKg 324 GAGAAUCAAGAGCUC 7826 24163 g.sub.Sa.sub.Sg.sub.Sc.sub.SucucUGAuGaggccguuaggccGaalauucucB 7942 IKKg 556 GAUGGCUGAGGAC 7827 24164 g.sub.Su.sub.Sc.sub.Sc.sub.SuccUGAuGaggccguuaggccGaalccaucB 7943 IKKg 556 AGAUGGCUGAGGACA 7828 24165 u.sub.Sg.sub.Su.sub.Sc.sub.ScuccUGAuGaggccguuaggccGaalccaucuB 7944 IKKg 568 ACAAGGCCUCUGUGA 7829 24166 u.sub.Sc.sub.Sa.sub.Sc.sub.SagacUGAuGaggccguuaggccGaalccuuguB 7945 IKKg 571 GGCCUCUGUGAAA 7830 24167 u.sub.Su.sub.Su.sub.Sc.sub.SaccUGAuGaggccguuaggccoaalaggccB 7946 IKKg 580 UGAAAGCCCAGGUGA 7831 24168 u.sub.Sc.sub.Sa.sub.Sc.sub.ScugcUGAuGaggccguuaggccGaalcuuucaB 7947 IKKg 749 GUGGACCAGCUGC 7832 24169 g.sub.Sc.sub.Sa.sub.Sg.sub.ScucUGAuGaggccguuaggccGaaluccacB 7948 lKKg 927 UGCAGCUGGAAGA 7833 24170 u.sub.Sc.sub.Su.sub.Su.sub.ScccUGAuGaggccguuaggccGaalcugcaB 7949 lKKg 927 AUGCAGCUGGAAGAU 7834 24171 a.sub.Su.sub.Sc.sub.Su.sub.SucccUGAuGaggccguuaggccGaalcugcauB 7950 IKKg 1012 GGAGGCCGAGCAG 7835 24172 c.sub.Su.sub.Sg.sub.Sc.sub.SuccUGAuGaggccguuaggccGaalccuccB 7951 IKKg 1012 AGGAGGCCGAGCAGC 7836 24173 g.sub.Sc.sub.Su.sub.Sg.sub.ScuccUGAuGaggccguuaggccGaalccuccuB 7952 IKKg 1020 AGCAGCACAAGAU 7837 24174 a.sub.Su.sub.Sc.sub.Su.sub.SugcUGAuGaggccguuaggccGaalcugcuB 7953 IKKg 1020 GAGCAGCACAAGAUU 7838 24175 a.sub.Sa.sub.Su.sub.Sc.sub.SuugcUGAuGaggccguuaggccGaalcugcucB 7954 IKKg 1022 GCAGCACAAGAUUGU 7839 24176 a.sub.Sc.sub.Sa.sub.Sa.sub.SucucUGAuGaggccguuaggccGaalugcugcB 7955 IKKg 1070 GGAUAUCUACAAGGC 7840 24177 g.sub.Sc.sub.Sc.sub.Su.sub.SugucUGAuGaggccguuaggccGaalauauccB 7956 IKKg 1143 AGGAGCAGCUGGA 7841 24178 u.sub.Sc.sub.Sc.sub.Sa.sub.SgccUGAuGaggccguuaggccGaalcuccuB 7957 IKKg 1350 AAGUGCCAGUAUCAG 7842 24179 c.sub.Su.sub.Sg.sub.Sa.sub.SuaccUGAuGaggccguuaggccGaalgcacuuB 7958 IKKg 1391 CAUGUCAUGGAGU 7843 24180 a.sub.Sc.sub.Su.sub.Sc.sub.ScacUGAuGaggccguuaggccGaalacaugB 7959 IKKg 1391 ACAUGUCAUGGAGUG 7844 24181 c.sub.Sa.sub.Sc.sub.Su.sub.SccacUGAuGaggccguuaggccGaalacauguB 7960 IKKg Control CACGUCUGCGGAA 7845 24182 u.sub.Su.sub.Sc.sub.Sc.sub.SgccUAGuGacgccguuaggcgGaalacgugB 7961 IKKg Control UCGGAACCAGGUCUG 7846 24183 c.sub.Sa.sub.Sg.sub.Sa.sub.SccucUAGuGacgccguuaggcgGaaluuccgaB 7962 IKKg 304 CCCUCCAGCGCUGCC 7847 24213 g.sub.Sg.sub.Sc.sub.Sa.sub.SgcggccgaaaggCgagugaGguCuuggagggB 7963 IKKg 306 CUCCAGCGCUGCCUG 7848 24214 c.sub.Sa.sub.Sg.sub.Sg.sub.ScaggccgaaaggCgagugaGguCugcuggagB 7964 IKKg 309 AGCGCUGCCUGGA 7849 24215 u.sub.Sc.sub.Sc.sub.Sa.sub.SgggccgaaaggCgagugaGguCuagcgcuB 7965 IKKg 328 UCAAGAGCUCCGA 7850 24216 u.sub.Sc.sub.Sg.sub.Sg.sub.SaggccgaaaggCgagugaGguCuucuugaB 7966

IKKg 328 AUCAAGAGCUCCGAG 7851 24217 c.sub.Su.sub.Sc.sub.Sg.sub.SgaggccgaaaggCgagugaGguCuucuugauB 7967 IKKg 572 GCCUCUGUGAAAG 7852 24218 c.sub.Su.sub.Su.sub.Su.sub.ScagccgaaaggCgagugaGguCuagaggcB 7968 IKKg 572 GGCCUCUGUGAAAGC 7853 24219 g.sub.Sc.sub.Su.sub.Su.sub.SucagccgaaaggCgagugaGguCuagaggccB 7969 IKKg 705 UGGAGAGUGAGCG 7854 24220 c.sub.Sg.sub.Sc.sub.Su.sub.ScagccgaaaggCgagugaGguCuucuccaB 7970 IKKg 1028 CAAGAUUGUGAUGGA 7855 24221 u.sub.Sc.sub.Sc.sub.Sa.sub.SucagccgaaaggCgagugaGguCuaaucuugB 7971 IKKg 1222 GAGGAAGCGGCAU 7856 24222 a.sub.Su.sub.Sg.sub.Sc.sub.ScggccgaaaggCgagugaGguCuuuccucB 7972 IKKg 1222 UGAGGAAGCGGCAUG 7857 24223 c.sub.Sa.sub.Su.sub.Sg.sub.SccggccgaaaggCgagugaGguCuuuccucaB 7973 IKKg 1351 AGUGCCAGUAUCAGG 7858 24224 c.sub.Sc.sub.Su.sub.Sg.sub.SauagccgaaaggCgagugaGguCuuggcacuB 7974 IKKg Control ACUCCGGCGUAGA 7859 24225 u.sub.Sc.sub.Su.sub.Sa.sub.ScggccgaaaggCuCugGagugagcggaguB 7975 IKKg Control GUGACGCGUGUCACA 7860 24226 u.sub.Sg.sub.Su.sub.Sg.sub.SacagccgaaaggCuCugGagugaggcgucacB 7976 IKKg 438 UGCAAGUUCCAGGAG 7861 24463 cuccuggCUGAUGAggccguuaggccGAAAcuugcaB 7977 IKKg 1167 AGGGAGUACAGCAAA 7862 24464 uuugcugCUGAUGAggccguuaggccGAAAcucccuB 7978 IKKg 1273 CCUACCUCUCCUCUC 7863 24465 gagaggaCUGAUGAggccguuaggccGAAAgguaggB 7979 IKKg 1639 CGCUGCUCUUUUUGU 7864 24466 acaaaaaCUGAUGAggccguuaggccGAAAgcagcgB 7980 IKKg 1781 GGCAGCUCUUCCUCC 7865 24467 ggaggaaCUGAUGAggccguuaggccGAAAgcugccB 7981 IKKg 741 AGCGUGCAGGUGGAC 7866 24468 guccaccCUGAUGAggccguuaggccGAAlcacgcuB 7982 IKKg 1158 CAGCUGCAGAGGGAG 7867 24469 cucccucCUGAUGAggccguuaggccGAAlcagcugB 7983 IKKg 1272 GCCUACCUCUCCUCU 7868 24470 agaggagCUGAUGAggccguuaggccGAAlguaggcB 7984 IKKg 1650 UUGUUCCCUUCUGUC 7869 24471 gacagaaCUGAUGAggccguuaggccGAAlgaacaaB 7985 IKKg 1834 UGCUGCCCUCUUACC 7870 24472 gguaagaCUGAUGAggccguuaggccGAAlgcagcaB 7986 IKKg 52 CAGAGAAGUGAGGAC 7871 24473 guccucagccgaaaggCgagugaGGuCuuucucugB 7987 IKKg 124 CAUCGAGGUCCCAUC 7872 24474 gaugggagccgaaaggCgagugaGGuCucucgaugB 7988 IKKg 1338 UUCUGCUGUCCCAAG 7873 24475 cuugggagccgaaaggCgagugaGGuCuagcagaaB 7989 IKKg 1633 CUGACUCGCUGCUCU 7874 24476 agagcaggccgaaaggCgagugaGGuCugagucagB 7990 IKKg 1655 CCCUUCUGUCUGCUC 7875 24477 gagcagagccgaaaggCgagugaGGuCuagaagggB 7991 IKKg 52 CAGAGAAGUGAGGAC 7871 24478 guccucaGGCTAGCTACAACGAuucucugB 7992 IKKg 216 GCAGCAGAUCAGGAC 7876 24479 guccugaGGCTAGCTACAACGAcugcugcB 7993 IKKg 538 UGAAGAGAUGCCAGC 7877 24480 gcuggcaGGCTAGCTACAACGAcucuucaB 7994 IKKg 868 UCCAAGAAUACGACA 7878 24481 ugucguaGGCTAGCTACAACGAucuuggaB 7995 IKKg 940 AUCUCAAACAGCAGC 7879 24482 gcugcugGGCTAGCTACAACGAuugagauB 7996 IKKg 52 CAGAGAAGUGAGGAC 7871 24483 guccucaGgaggaaacucCCUUCaaggacaucgucCGGGuucucugB 7997 IKKg 215 GGCAGCAGAUCAGGA 7880 24484 uccugauGgaggaaacucCCUUCaaggacaucgucCGGGugcugccB 7998 IKKg 817 CGGAGGAGAAGAGGA 7881 24485 uccucuuGgaggaaacucCCUUCaaggacaucgucCGGGuccuccgB 7999 IKKg 986 ACAGGAGGUGAUCGA 7882 24486 ucgaucaGgaggaaacucCCUUCaaggacaucgucCGGGcuccuguB 8000 IKKg 1826 CCUGGGAGUGCUGCC 7883 24487 ggcagcaGgaggaaacucCCUUCaaggacaucgucCGGGucccaggB 8001 A, G, C, U = Ribo A, G, C, T (italic) = deoxy lower case = 2'-O-methyl s = phosphorothioate 3'-internucleotide linkage U = 2'-deoxy-2'-C-allyl uridine U = 2'-deoxy-2'-Amino uridine C = 2'-deoxy-2'-Amino cytidine I = Inosine B = inverted deoxyabasic derivative

[0276]

Sequence CWU 0 SQTB SEQUENCE LISTING The patent application contains a lengthy "Sequence Listing" section. A copy of the "Sequence Listing" is available in electronic form from the USPTO web site (http://seqdata.uspto.gov/?pageRequest=docDetail&DocID=US20060154271A1). An electronic copy of the "Sequence Listing" will also be available from the USPTO upon request and payment of the fee set forth in 37 CFR 1.19(b)(3).

0 SQTB SEQUENCE LISTING The patent application contains a lengthy "Sequence Listing" section. A copy of the "Sequence Listing" is available in electronic form from the USPTO web site (http://seqdata.uspto.gov/?pageRequest=docDetail&DocID=US20060154271A1). An electronic copy of the "Sequence Listing" will also be available from the USPTO upon request and payment of the fee set forth in 37 CFR 1.19(b)(3).

Claims

1. A chemically modified double stranded siRNA molecule that down regulates expression of a protein kinase PKR gene via RNA interference (RNAi), wherein: a) each strand of said siRNA molecule is independently about 18 to about 28 nucleotides in length; and b) one strand of said siRNA molecule comprises nucleotide sequence having sufficient complementarity to an RNA of said protein kinase PKR gene for the siRNA molecule to direct cleavage of said RNA via RNA interference.

2. The siRNA molecule of claim 1, wherein each strand of the siRNA molecule comprises about 18 to about 28 nucleotides, and wherein each strand comprises at least about 14 to 24 nucleotides that are complementary to the nucleotides of the other strand.

3. The siRNA molecule of claim 1, wherein said siNA molecule is assembled from two separate oligonucleotide fragments wherein a first fragment comprises the sense strand and a second fragment comprises the antisense strand of said siNA molecule.

4. The siRNA molecule of claim 3, wherein said sense strand is connected to the antisense strand via a linker molecule.

5. The siRNA molecule of claim 4, wherein said linker molecule is a polynucleotide linker.

6. The siRNA molecule of claim 4, wherein said linker molecule is a non-nucleotide linker.

7. The siRNA molecule of claim 1, wherein said siRNA molecule comprises at least one 2'-sugar modification.

8. The siRNA molecule of claim 1, wherein said siRNA molecule comprises at least one nucleic acid base modification.

9. The siRNA molecule of claim 1, wherein said siRNA molecule comprises at least one phosphate backbone modification.

10. The siRNA molecule of claim 7, wherein said 2'-sugar modification is a 2'-deoxy-2'-fluoro modification.

11. The siRNA molecule of claim 7, wherein said 2'-sugar modification is a 2'-O-methyl modification.

12. The siRNA molecule of claim 7, wherein said 2'-sugar modification is a 2'-deoxy modification.

13. The siRNA molecule of claim 3, wherein said second fragment comprises a terminal cap moiety at a 5'-end, a 3'-end, or both of the 5' and 3' ends of said second strand.

14. The siRNA molecule of claim 13, wherein said terminal cap moiety is an inverted deoxy abasic moiety.

15. The siRNA molecule of claim 3, wherein said first fragment comprises a phosphorothioate internucleotide linkage at the 3' end of said first strand.

16. A composition comprising the siRNA molecule of claim 1 in a pharmaceutically acceptable carrier or diluent.