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Patent US20070050146 - Micrornas and uses thereof - Google PatentsSearch Images Maps Play YouTube News Gmail Drive More »Sign inAdvanced Patent SearchPatentsDescribed herein are novel polynucleotides associated with prostate and lung cancer. The polynucleotides are miRNAs and miRNA precursors. Related methods and compositions that can be used for diagnosis, prognosis, and treatment of those medical conditions are disclosed. Also described herein are methods...http://www.google.com/patents/US20070050146?utm_source=gb-gplus-sharePatent US20070050146 - Micrornas and uses thereofAdvanced Patent SearchPublication numberUS20070050146 A1Publication typeApplicationApplication numberUS 11/130,645Publication dateMar 1, 2007Filing dateMay 16, 2005Priority dateMay 14, 2004Also published asCA2566519A1, EP1784501A2, EP2322650A1, EP2322650A8, US7709616, US8461315, US20110213007, US20110223656, US20120094374, US20140017780, WO2005111211A2, WO2005111211A3, WO2005111211A8Publication number11130645, 130645, US 2007/0050146 A1, US 2007/050146 A1, US 20070050146 A1, US 20070050146A1, US 2007050146 A1, US 2007050146A1, US-A1-20070050146, US-A1-2007050146, US2007/0050146A1, US2007/050146A1, US20070050146 A1, US20070050146A1, US2007050146 A1, US2007050146A1InventorsItzhak Bentwich, Amir Avniel, Yael Karov, Ranit AharonovOriginal AssigneeItzhak Bentwich, Amir Avniel, Yael Karov, Ranit AharonovExport CitationBiBTeX, EndNote, RefManReferenced by (77), Classifications (23), Legal Events (2) External Links: USPTO, USPTO Assignment, EspacenetMicrornas and uses thereof
US 20070050146 A1Abstract
Described herein are novel polynucleotides associated with prostate and lung cancer. The polynucleotides are miRNAs and miRNA precursors. Related methods and compositions that can be used for diagnosis, prognosis, and treatment of those medical conditions are disclosed. Also described herein are methods that can be used to identify modulators of prostate and lung cancer. Images(5) Claims(17)
1. An isolated nucleic acid comprising a sequence selected from the group consisting of: (a) the sequence of a hairpin referred to in Table 1; (b) the sequence of sequence identifiers 6757248-6894882 of the Sequence Listing of U.S. patent application Ser. No. 10/709,572; (c) the sequence of sequence identifiers 1-6318 or 18728-18960 of the Sequence Listing of U.S. Provisional Patent Application No. 60/655,094; (d) the sequence of a miRNA referred to in Table 1; (e) the sequence of sequence identifiers 1-117750 or 6894883-10068177 of the Sequence Listing of U.S. patent application Ser. No. 10/709,572; (f) the sequence of sequence identifiers 6319-18727 or 18961-19401 of the Sequence Listing of U.S. Provisional Patent Application No. 60/655,094; (g) the sequence of a target gene binding site referred to in Table 4; (h) the sequence of sequence identifiers 117751-6757247 of the Sequence Listing of U.S. patent application Ser. No. 10/709,572; (i) complement of (a)-(h); (j) nucleotide sequence comprising at least 12 contiguous nucleotides at least 60% identical to (a)-(h); wherein the nucleic acid is from 5-250 nucleotides in length. 2. A probe comprising the nucleic acid of claim 1. 3. The probe of claim 2 wherein the nucleic acid comprises at least 8-22 contiguous nucleotides complementary to a miRNA referred to in Table 2 as differentially expressed in prostate cancer or lung cancer. 4. A plurality of probes of claim 3. 5. The plurality of probes of claim 4 comprising at least one probe complementary to each miRNA referred to in Table 2 as differentially expressed in prostate cancer. 6. The plurality of probes of claim 4 comprising at least one probe complementary to each miRNA referred to in Table 2 as differentially expressed in lung cancer. 7. A composition comprising the plurality of probes of claim 3. 8. A biochip comprising a solid substrate, said substrate comprising a plurality of probes of claim 3, wherein each probe is attached to the substrate at a spatially defined address. 9. The biochip of claim 8 wherein the probes are complementary to a miRNA referred to in Table 2 as differentially expressed in prostate cancer. 10. The biochip of claim 8 wherein the probes are complementary to a miRNA referred to in Table 2 as differentially expressed in lung cancer. 11. A method for detecting differential expression of a miRNA comprising: (a) providing a biological sample; and (b) measuring the level of a nucleic acid at least 70% identical to (i) a sequence of a miRNA referred to in Table 1, (ii) the sequence of sequence identifiers 1-117750 or 6894883-10068177 of the Sequence Listing of U.S. patent application Ser. No. 10/709,572, (iii) the sequence of sequence identifiers 6319-18727 or 18961-19401 of the Sequence Listing of U.S. Provisional Patent Application No. 60/655,094, or (iv) a variant of (i)-(iii), wherein a difference in the level of the nucleic acid compared to a control is indicative of differential expression. 12. A method for identifying a compound that modulates expression of a miRNA: (a) providing a cell that is capable of expressing a nucleic acid at least 70% identical to (i) a sequence of a miRNA referred to in Table 1, (ii) the sequence of sequence identifiers 1-117750 or 6894883-10068177 of the Sequence Listing of U.S. patent application Ser. No. 10/709,572, (iii) the sequence of sequence identifiers 6319-18727 or 18961-19401 of the Sequence Listing of U.S. Provisional Patent Application No. 60/655,094, or (iv) a variant of (i)-(iii); (b) contacting the cell with a candidate modulator; and (c) measuring the level of expression of the nucleic acid, wherein a difference in the level of the nucleic acid compared to a control identifies the compound as a modulator of expression of the miRNA. 13. A method of inhibiting expression of a target gene in a cell comprising introducing a nucleic acid into the cell in an amount sufficient to inhibit expression of the target gene, wherein the target gene comprises a (i) binding site substantially identical to a binding site referred to in Table 4, (ii) sequence of sequence identifiers 117751-6757247 of the Sequence Listing of U.S. patent application Ser. No. 10/709,572, or (iii) a variant of (i) or (ii); and wherein the nucleic acid comprises a sequence (a) of SEQ ID NOS: 1-760616, (b) sequence of sequence identifiers 1-117750 and 6757248-10068177 of the Sequence Listing of U.S. patent application Ser. No. 10/709,572, (c) a sequence set forth on the Sequence Listing of U.S. Provisional Patent Application No. 60/655,094, or (d) a variant of (a)-(c). 14. The method of claim 12 wherein expression is inhibited in vitro or in vivo. 15. A method of increasing expression of a target gene in a cell comprising introducing a nucleic acid into the cell in an amount sufficient to increase expression of the target gene, wherein the target gene comprises a (i) binding site substantially identical to a binding site referred to in Table 4, (ii) sequence of sequence identifiers 117751-6757247 of the Sequence Listing of U.S. patent application Ser. No. 10/709,572, or (iii) a variant of (i) or (ii); wherein the nucleic acid comprises a sequence substantially complementary to a sequence (a) of SEQ ID NOS: 1-760616, (b) set forth on the Sequence Listing of U.S. patent application Ser. No. 10/709,572, (c) a sequence set forth on the Sequence Listing of U.S. Provisional Patent Application No. 60/655,094, or (d) a variant of (a)-(c). 16. The method of claim 15 wherein expression is inhibited in vitro or in vivo. 17. A method of treating a patient with a disorder set forth on Table 6 comprising administering to a patient in need thereof a composition comprising the nucleic acid of claim 1. Description
CROSS REFERENCE TO RELATED APPLICATIONS The present application is a continuation of the International Application of Bentwich et al., entitled “MICRORNAS AND USES THEREOF,” filed May 14, 2005, which is a continuation-in-part of U.S. application Ser. No. 10/709,577, filed May 14, 2004, and U.S. application Ser. No. 10/709,572, filed May 14, 2004, and which claims the benefit of U.S. Provisional Application No. 60/666,340, filed Mar. 30, 2005, U.S. Provisional Application No. 60/665,094, filed Mar. 25, 2005, U.S. Provisional Application No. 60/662,742, filed Mar. 17, 2005, U.S. Provisional Application No. 60/593,329, filed Jan. 6, 2005, U.S. Provisional Application No. 60/593,081, filed Dec. 8, 2004, U.S. Provisional Application No. 60/522,860, filed Nov. 15, 2004, U.S. Provisional Application No. 60/522,457, filed Oct. 4, 2004, U.S. Provisional Application No. 60/522,452, filed Oct. 3, 2004, and U.S. Provisional Application No. 60/522,449, filed Oct. 3, 2004, the contents of which are incorporated herein by reference.
FIELD OF THE INVENTION The invention relates in general to microRNA molecules as well as various nucleic acid molecules relating thereto or derived therefrom. BACKGROUND OF THE INVENTION MicroRNAs (miRNAs) are short RNA oligonucleotides of approximately 22 nucleotides that are involved in gene regulation. MicroRNAs regulate gene expression by targeting mRNAs for cleavage or translational repression. Although miRNAs are present in a wide range of species including C. elegans, Drosophilla and humans, they have only recently been identified. More importantly, the role of miRNAs in the development and progression of disease has only recently become appreciated. As a result of their small size, miRNAs have been difficult to identify using standard methodologies. A limited number of miRNAs have been identified by extracting large quantities of RNA. MiRNAs have also been identified that contribute to the presentation of visibly discernable phenotypes. Expression array data shows that miRNAs are expressed in different developmental stages or in different tissues. The restriction of miRNAs to certain tissues or at limited developmental stages indicates that the miRNAs identified to date are likely only a small fraction of the total miRNAs. Computational approaches have recently been developed to identify the remainder of miRNAs in the genome. Tools such as MiRscan and MiRseeker have identified miRNAs that were later experimentally confirmed. Based on these computational tools, it has been estimated that the human genome contains 200-255 miRNA genes. These estimates are based on an assumption, however, that the miRNAs remaining to be identified will have the same properties as those miRNAs already identified. Based on the fundamental importance of miRNAs in mammalian biology and disease, the art needs to identify unknown miRNAs. The present invention satisfies this need and provides a significant number of miRNAs and uses therefore. SUMMARY OF THE INVENTION The present invention is related to an isolated nucleic acid comprising a sequence of a pri-miRNA, pre-miRNA, miRNA, miRNA*, anti-miRNA, or a miRNA binding site, or a variant thereof. The nucleic acid may comprise the sequence of a hairpin referred to in Table 1; the sequence of sequence identifiers 6757248-6894882 of the Sequence Listing of U.S. patent application Ser. No. 10/709,572, which is incorporated herein by reference; the sequence of sequence identifiers 1-6318 or 18728-18960 of the Sequence Listing of U.S. Provisional Patent Application No. 60/655,094, which is incorporated herein by reference; the sequence of a miRNA referred to in Table 1; the sequence of sequence identifiers 1-117750 or 6894883-10068177 of the Sequence Listing of U.S. patent application Ser. No. 10/709,572, which is incorporated herein by reference; the sequence of sequence identifiers 6319-18727 or 18961-19401 of the Sequence Listing of U.S. Provisional Patent Application No. 60/655,094, which is incorporated herein by reference; the sequence of a target gene binding site referred to in Table 4; the sequence of sequence identifiers 117751-6757247 of the Sequence Listing of U.S. patent application Ser. No. 10/709,572, which is incorporated herein by reference; a complement thereof; or a sequence comprising at least 12 contiguous nucleotides at least 60% identical thereto. The isolated nucleic acid may be from 5-250 nucleotides in length. The present invention is also related to a probe comprising the nucleic acid. The probe may comprise at least 8-22 contiguous nucleotides complementary to a miRNA referred to in Table 2 as differentially expressed in prostate cancer or lung cancer. The present invention is also related to a plurality of the probes. The plurality of probes may comprise at least one probe complementary to each miRNA referred to in Table 2 as differentially expressed in prostate cancer. The plurality of probes may also comprise at least one probe complementary to each miRNA referred to in Table 2 as differentially expressed in lung cancer. The present invention is also related to a composition comprising a probe or plurality of probes. The present invention is also related to a biochip comprising a solid substrate, said substrate comprising a plurality of probes. Each of the probes may be attached to the substrate at a spatially defined address. The biochip may comprise probes that are complementary to a miRNA referred to in Table 2 as differentially expressed in prostate cancer. The biochip may also comprise probes that are complementary to a miRNA referred to in Table 2 as differentially expressed in lung cancer. The present invention is also related to a method of detecting differential expression of a disease-associated miRNA. A biological sample may be provide and the level of a nucleic acid measured that is at least 70% identical to a sequence of a miRNA referred to in Table 1; the sequence of sequence identifiers 1-117750 or 6894883-10068177 of the Sequence Listing of U.S. patent application Ser. No. 10/709,572, which is incorporated herein by reference; the sequence of sequence identifiers 6319-18727 or 18961-19401 of the Sequence Listing of U.S. Provisional Patent Application No. 60/655,094, which is incorporated herein by reference; or variants thereof. A difference in the level of the nucleic acid compared to a control is indicative of differential expression. The present invention is also related to a method of identifying a compound that modulates a pathological condition. A cell may be provided that is capable of expressing a nucleic acid at least 70% identical to a sequence of a miRNA referred to in Table 1; the sequence of sequence identifiers 1-117750 or 6894883-10068177 of the Sequence Listing of U.S. patent application Ser. No. 10/709,572, which is incorporated herein by reference; the sequence of sequence identifiers 6319-18727 or 18961-19401 of the Sequence Listing of U.S. Provisional Patent Application No. 60/655,094, which is incorporated herein by reference; or variants thereof. The cell may be contacted with a candidate modulator and then measuring the level of expression of the nucleic acid. A difference in the level of the nucleic acid compared to a control identifies the compound as a modulator of a pathological condition associated with the nucleic acid. The present invention is also related to a method of inhibiting expression of a target gene in a cell. Into the cell, a nucleic acid may be introduced in an amount sufficient to inhibit expression of the target gene. The target gene may comprise a binding site substantially identical to a binding site referred to in Table 4; a sequence of sequence identifiers 117751-6757247 of the Sequence Listing of U.S. patent application Ser. No. 10/709,572, which is incorporated herein by reference; or a variant thereof. The nucleic acid may comprise a sequence of SEQ ID NOS: 1-760616; a sequence of sequence identifiers 1-117750 and 6757248-10068177 of the Sequence Listing of U.S. patent application Ser. No. 10/709,572, which is incorporated herein by reference; a sequence set forth on the Sequence Listing of U.S. Provisional Patent Application No. 60/655,094, which is incorporated herein by reference; or a variant thereof. Expression of the target gene may be inhibited in vitro or in vivo. The present invention is also related to a method of increasing expression of a target gene in a cell. Into the cell, a nucleic acid may be introduced in an amount sufficient to inhibit expression of the target gene. The target gene may comprise a binding site substantially identical to a binding site referred to in Table 4; a sequence of sequence identifiers 117751-6757247 of the Sequence Listing of U.S. patent application Ser. No. 10/709,572, which is incorporated herein by reference; or a variant thereof. The nucleic acid may comprise a sequence substantially complementary to SEQ ID NOS: 1-760616; a sequence of sequence identifiers 1-117750 and 6757248-10068177 of the Sequence Listing of U.S. patent application Ser. No. 10/709,572, which is incorporated herein by reference; a sequence set forth on the Sequence Listing of U.S. Provisional Patent Application No. 60/655,094, which is incorporated herein by reference; or a variant thereof. Expression of the target gene may be inhibited in vitro or in vivo. Expression of the target gene may be increased in vitro or in vivo. The present invention is also related to a method of treating a patient with a disorder set forth on Table 6 comprising administering to a patient in need thereof a nucleic acid comprising a sequence of SEQ ID NOS: 1-760616; a sequence set forth on the Sequence Listing of U.S. patent application Ser. No. 10/709,572, which is incorporated herein by reference; a sequence set forth on the Sequence Listing of U.S. Provisional Patent Application No. 60/655,094, which is incorporated herein by reference; or a variant thereof. BRIEF DESCRIPTION OF SEQUENCE LISTING AND TABLES Reference is made to the appendix submitted on the compact submitted herewith. The compact disc contains SEQUENCE LISTING.TXT (161.453 MB, May 11, 2005), which is a Sequence Listing in accordance with 37 C.F.R. �� 1.821-1.825, and the following tables: TABLE 1.TXT (968 KB, May 12, 2005); TABLE 2.TXT (1.327 MB, May 12, 2005); TABLE 4.TXT (10.857 MB, May 12, 2005); and TABLE 5.TXT (986 KB, May 12, 2005), the contents of which are incorporated by reference herein. LENGTHY TABLES FILED ON CD The patent application contains a lengthy table section. A copy of the table is available in electronic form from the USPTO web site (http://seqdata.uspto.gov/?pageRequest=docDetail&DocID=US20070050146A1). An electronic copy of the table will also be available from the USPTO upon request and payment of the fee set forth in 37 CFR 1.19(b)(3). BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 demonstrates a model of maturation for miRNAs. FIG. 2 shows a schematic illustration of the MC19 cluster on 19q13.42. Panel A shows the ˜500,000 bp region of chromosome 19, from 58,580,001 to 59,080,000 (according to the May 2004 USCS assembly), in which the cluster is located including the neighboring protein-coding genes. The MC19-1 cluster is indicated by a rectangle. Mir-371, mir-372, and mir-373 are indicted by lines. Protein coding genes flanking the cluster are represented by large arrow-heads. Panel B shows a detailed structure of the MC19-1 miRNA cluster. A region of ˜102,000 bp, from 58,860,001 to 58,962,000 (according to the May 2004 USCS assembly), is presented. MiRNA precursors are represented by a black bars. It should be noted that all miRNAs are at the same orientation from left to right. Shaded areas around miRNA precursors represent repeating units in which the precursor is embedded. The location of mir-371, mir-372, and mir-373, is also presented. FIG. 3 is a graphical representation of multiple sequence alignment of 35 human repeat units at distinct size of ˜690 nt (A) and 26 chimpanzees repeat units (B). The graph was generated by calculating a similarity score for each position in the alignment with an averaging sliding window of 10 nt (Maximum score-1, minimum score-0). The repeat unit sequences were aligned by ClustalW program. Each position of the resulting alignment was assigned a score which represented the degree of similarity at this position. The region containing the miRNA precursors is bordered by vertical lines. The exact location of the mature miRNAs derived from the 5′ stems (5p) and 3′ stems (3p) of the precursors is indicted by vertical lines. FIG. 4 shows sequence alignments of the 43 A-type pre-miRNAs of the MC19-1 cluster. Panel A shows the multiple sequence alignment with the Position of the mature miRNAs marked by a frame. The consensus sequence is shown at the bottom. Conserved nucleotides are colored as follows: black-100%, dark grey-80% to 99%, and clear grey-60% to 79%. Panel B shows alignments of consensus mature A-type miRNAs with the upstream human cluster of mir -371, mir-372, miR-373. Panel C shows alignments of consensus mature A-type miRNAs with the hsa-mir-371-373 mouse orthologous cluster. FIG. 5 shows expression analysis of the MC19-1 miRNAs. Panel A shows a Northern blot analysis of two selected A-type miRNAs. Expression was analyzed using total RNA from human brain (B), liver (L), thymus (T), placenta (P) and HeLa cells (H). The expression of mir-98 and ethidium bromide staining of the tRNA band served as control. Panel B shows RT-PCR analysis of the mRNA transcript containing the A-type miRNA precursors. Reverse transcription of 5�g total RNA from placenta was performed using oligo-dT. This was followed by PCR using the denoted primers (indicated by horizontal arrows). The region examined is illustrated at the top. Vertical black bars represent the pre-miRNA; shaded areas around the pre-miRNAs represent the repeating units; the location of four ESTs is indicted at the right side; the poly-A site, as found in the ESTs and located downstream to a AATAAA consensus, is indicated by a vertical arrow. The fragments expected from RT-PCR using three primer combinations are indicated below the illustration of the cluster region. The results of the RT-PCR analysis are presented below the expected fragments. Panel C shows the sequencing strategy of the FR2 fragment. The fragment was cloned into the pTZ57R\T vector and sequenced using external and internal primers.
DETAILED DESCRIPTION The present invention provides nucleotide sequences of miRNAs, precursors thereto, targets thereof and related sequences. Such nucleic acids are useful for diagnostic purposes, and also for modifying target gene expression. Other aspects of the invention will become apparent to the skilled artisan by the following description of the invention. 1. Definitions Before the present compounds, products and compositions and methods are disclosed and described, it is to be understood that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting. It must be noted that, as used in the specification and the appended claims, the singular forms “a,” “an” and “the” include plural referents unless the context clearly dictates otherwise. a. Animal “Animal” as used herein may mean fish, amphibians, reptiles, birds, and mammals, such as mice, rats, rabbits, goats, cats, dogs, cows, apes and humans. b. Attached “Attached” or “immobilized” as used herein to refer to a probe and a solid support may mean that the binding between the probe and the solid support is sufficient to be stable under conditions of binding, washing, analysis, and removal. The binding may be covalent or non-covalent. Covalent bonds may be formed directly between the probe and the solid support or may be formed by a cross linker or by inclusion of a specific reactive group on either the solid support or the probe or both molecules. Non-covalent binding may be one or more of electrostatic, hydrophilic, and hydrophobic interactions. Included in non-covalent binding is the covalent attachment of a molecule, such as streptavidin, to the support and the non-covalent binding of a biotinylated probe to the streptavidin. Immobilization may also involve a combination of covalent and non-covalent interactions. c. Biological Sample “Biological sample” as used herein may mean a sample of biological tissue or fluid that comprises nucleic acids. Such samples include, but are not limited to, tissue isolated from animals. Biological samples may also include sections of tissues such as biopsy and autopsy samples, frozen sections taken for histologic purposes, blood, plasma, serum, sputum, stool, tears, mucus, hair, and skin. Biological samples also include explants and primary and/or transformed cell cultures derived from patient tissues. A biological sample may be provided by removing a sample of cells from an animal, but can also be accomplished by using previously isolated cells (e.g., isolated by another person, at another time, and/or for another purpose), or by performing the methods of the invention in vivo. Archival tissues, such as those having treatment or outcome history, may also be used. d. Complement “Complement” or “complementary” as used herein may mean Watson-Crick or Hoogsteen base pairing between nucleotides or nucleotide analogs of nucleic acid molecules. e. Differential Expression “Differential expression” may mean qualitative or quantitative differences in the temporal and/or cellular gene expression patterns within and among cells and tissue. Thus, a differentially expressed gene can qualitatively have its expression altered, including an activation or inactivation, in, e.g., normal versus disease tissue. Genes may be turned on or turned off in a particular state, relative to another state thus permitting comparison of two or more states. A qualitatively regulated gene will exhibit an expression pattern within a state or cell type which may be detectable by standard techniques. Some genes will be expressed in one state or cell type, but not in both. Alternatively, the difference in expression may be quantitative, e.g., in that expression is modulated, either up-regulated, resulting in an increased amount of transcript, or down-regulated, resulting in a decreased amount of transcript. The degree to which expression differs need only be large enough to quantify via standard characterization techniques such as expression arrays, quantitative reverse transcriptase PCR, northern analysis, and RNase protection. f. Gene “Gene” used herein may be a genomic gene comprising transcriptional and/or translational regulatory sequences and/or a coding region and/or non-translated sequences (e.g., introns, 5′- and 3′-untranslated sequences). The coding region of a gene may be a nucleotide sequence coding for an amino acid sequence or a functional RNA, such as tRNA, rRNA, catalytic RNA, siRNA, miRNA and antisense RNA. A gene may also be an mRNA or cDNA corresponding to the coding regions (e.g., exons and miRNA) optionally comprising 5′- or 3′-untranslated sequences linked thereto. A gene may also be an amplified nucleic acid molecule produced in vitro comprising all or a part of the coding region and/or 5′- or 3′-untranslated sequences linked thereto. g. Host Cell “Host cell” used herein may be a naturally occurring cell or a transformed cell that contains a vector and supports the replication of the vector. Host cells may be cultured cells, explants, cells in vivo, and the like. Host cells may be prokaryotic cells such as E. coli, or eukaryotic cells such as yeast, insect, amphibian, or mammalian cells, such as CHO, HeLa. h. Identity “Identical” or “identity” as used herein in the context of two or more nucleic acids or polypeptide sequences, may mean that the sequences have a specified percentage of nucleotides or amino acids that are the same over a specified region. The percentage may be calculated by comparing optimally aligning the two sequences, comparing the two sequences over the specified region, determining the number of positions at which the identical residue occurs in both sequences to yield the number of matched positions, dividing the number of matched positions by the total number of positions in the specified region, and multiplying the result by 100 to yield the percentage of sequence identity. In cases where the two sequences are of different lengths or the alignment produces staggered end and the specified region of comparison includes only a single sequence, the residues of single sequence are included in the denominator but not the numerator of the calculation. When comparing DNA and RNA, thymine (T) and uracil (U) are considered equivalent. Identity may be performed manually or by using computer sequence algorithm such as BLAST or BLAST 2.0. i. Label “Label” as used herein may mean a composition detectable by spectroscopic, photochemical, biochemical, immunochemical, chemical, or other physical means. For example, useful labels include 32P, fluorescent dyes, electron-dense reagents, enzymes (e.g., as commonly used in an ELISA), biotin, digoxigenin, or haptens and other entities which can be made detectable. A label may be incorporated into nucleic acids and proteins at any position. j. Nucleic Acid “Nucleic acid” or “oligonucleotide” or “polynucleotide” used herein may mean at least two nucleotides covalently linked together. As will be appreciated by those in the art, the depiction of a single strand also defines the sequence of the complementary strand. Thus, a nucleic acid also encompasses the complementary strand of a depicted single strand. As will also be appreciated by those in the art, many variants of a nucleic acid may be used for the same purpose as a given nucleic acid. Thus, a nucleic acid also encompasses substantially identical nucleic acids and complements thereof. As will also be appreciated by those in the art, a single strand provides a probe for a probe that may hybridize to the target sequence under stringent hybridization conditions. Thus, a nucleic acid also encompasses a probe that hybridizes under stringent hybridization conditions. Nucleic acids may be single stranded or double stranded, or may contain portions of both double stranded and single stranded sequence. The nucleic acid may be DNA, both genomic and cDNA, RNA, or a hybrid, where the nucleic acid may contain combinations of deoxyribo- and ribo-nucleotides, and combinations of bases including uracil, adenine, thymine, cytosine, guanine, inosine, xanthine hypoxanthine, isocytosine and isoguanine. Nucleic acids may be obtained by chemical synthesis methods or by recombinant methods. A nucleic acid will generally contain phosphodiester bonds, although nucleic acid analogs may be included that may have at least one different linkage, e.g., phosphoramidate, phosphorothioate, phosphorodithioate, or O-methylphosphoroamidite linkages and peptide nucleic acid backbones and linkages. Other analog nucleic acids include those with positive backbones; non-ionic backbones, and non-ribose backbones, including those described in U.S. Pat. Nos. 5,235,033 and 5,034,506, which are incorporated by reference. Nucleic acids containing one or more non-naturally occurring or modified nucleotides are also included within one definition of nucleic acids. The modified nucleotide analog may be located for example at the 5′-end and/or the 3′-end of the nucleic acid molecule. Representative examples of nucleotide analogs may be selected from sugar- or backbone-modified ribonucleotides. It should be noted, however, that also nucleobase-modified ribonucleotides, i.e. ribonucleotides, containing a non-naturally occurring nucleobase instead of a naturally occurring nucleobase such as uridines or cytidines modified at the 5-position, e.g. 5-(2-amino)propyl uridine, 5-bromo uridine; adenosines and guanosines modified at the 8-position, e.g. 8-bromo guanosine; deaza nucleotides, e.g. 7-deaza-adenosine; O- and N-alkylated nucleotides, e.g. N6-methyl adenosine are suitable. The 2′-OH-group may be replaced by a group selected from H, OR, R, halo, SH, SR, NH2, NHR, NR2 or CN, wherein R is C1-C6 alkyl, alkenyl or alkynyl and halo is F, Cl, Br or I. Modifications of the ribose-phosphate backbone may be done for a variety of reasons, e.g., to increase the stability and half-life of such molecules in physiological environments or as probes on a biochip. Mixtures of naturally occurring nucleic acids and analogs may be made; alternatively, mixtures of different nucleic acid analogs, and mixtures of naturally occurring nucleic acids and analogs may be made. k. Operably Linked “Operably linked” used herein may mean that expression of a gene is under the control of a promoter with which it is spatially connected. A promoter may be positioned 5′ (upstream) or 3′ (downstream) of the gene under its control. The distance between the promoter and the gene may be approximately the same as the distance between that promoter and the gene it controls in the gene from which the promoter is derived. As is known in the art, variation in this distance can be accommodated without loss of promoter function. l. Probe “Probe” as used herein may mean an oligonucleotide capable of binding to a target nucleic acid of complementary sequence through one or more types of chemical bonds, usually through complementary base pairing, usually through hydrogen bond formation. Probes may bind target sequences lacking complete complementarity with the probe sequence depending upon the stringency of the hybridization conditions. There may be any number of base pair mismatches which will interfere with hybridization between the target sequence and the single stranded nucleic acids of the present invention. However, if the number of mutations is so great that no hybridization can occur under even the least stringent of hybridization conditions, the sequence is not a complementary target sequence. A probe may be single stranded or partially single and partially double stranded. The strandedness of the probe is dictated by the structure, composition, and properties of the target sequence. Probes may be directly labeled or indirectly labeled such as with biotin to which a streptavidin complex may later bind. m. Promoter “Promoter” as used herein may mean a synthetic or naturally-derived molecule which is capable of conferring, activating or enhancing expression of a nucleic acid in a cell. A promoter may comprise one or more specific regulatory elements to further enhance expression and/or to alter the spatial expression and/or temporal expression of same. A promoter may also comprise distal enhancer or repressor elements, which can be located as much as several thousand base pairs from the start site of transcription. A promoter may be derived from sources including viral, bacterial, fungal, plants, insects, and animals. A promoter may regulate the expression of a gene component constitutively, or differentially with respect to cell, the tissue or organ in which expression occurs or, with respect to the developmental stage at which expression occurs, or in response to external stimuli such as physiological stresses, pathogens, metal ions, or inducing agents. Representative examples of promoters include the bacteriophage T7 promoter, bacteriophage T3 promoter, SP6 promoter, lac operator-promoter, tac promoter, SV40 late promoter, SV40 early promoter, RSV-LTR promoter, CMV IE promoter, SV40 early promoter or SV40 late promoter and the CMV IE promoter. n. Selectable Marker “Selectable marker” used herein may mean any gene which confers a phenotype on a cell in which it is expressed to facilitate the identification and/or selection of cells which are transfected or transformed with a genetic construct. Representative examples of selectable markers include the ampicillin-resistance gene (Ampr), tetracycline-resistance gene (Tcr), bacterial kanamycin-resistance gene (Kanr), zeocin resistance gene, the AURI-C gene which confers resistance to the antibiotic aureobasidin A, phosphinothricin-resistance gene, neomycin phosphotransferase gene (nptII), hygromycin-resistance gene, beta-glucuronidase (GUS) gene, chloramphenicol acetyltransferase (CAT) gene, green fluorescent protein-encoding gene and luciferase gene. o. Stringent Hybridization Conditions “Stringent hybridization conditions” used herein may mean conditions under which a first nucleic acid sequence (e.g., probe) will hybridize to a second nucleic acid sequence (e.g., target), such as in a complex mixture of nucleic acids, but to no other sequences. Stringent conditions are sequence-dependent and will be different in different circumstances. Generally, stringent conditions are selected to be about 5-10� C. lower than the thermal melting point (Tm) for the specific sequence at a defined ionic strength pH. The Tm may be the temperature (under defined ionic strength, pH, and nucleic concentration) at which 50% of the probes complementary to the target hybridize to the target sequence at equilibrium (as the target sequences are present in excess, at Tm, 50% of the probes are occupied at equilibrium). Stringent conditions may be those in which the salt concentration is less than about 1.0 M sodium ion, typically about 0.01-1.0 M sodium ion concentration (or other salts) at pH 7.0 to 8.3 and the temperature is at least about 30� C. for short probes (e.g., about 10-50 nucleotides) and at least about 60� C. for long probes (e.g., greater than about 50 nucleotides). Stringent conditions may also be achieved with the addition of destabilizing agents such as formamide. For selective or specific hybridization, a positive signal may be at least 2 to 10 times background hybridization. Exemplary stringent hybridization conditions include the following: 50% formamide, 5� SSC, and 1% SDS, incubating at 42� C., or, 5� SSC, 1% SDS, incubating at 65� C., with wash in 0.2�SSC, and 0.1% SDS at 65� C. p. Substantially Complementary “Substantially complementary” used herein may mean that a first sequence is at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 97%, 98% or 99% identical to the complement of a second sequence over a region of 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 30, 35, 40, 45, 50 or more nucleotides, or that the two sequences hybridize under stringent hybridization conditions. q. Substantially Identical “Substantially identical” used herein may mean that a first and second sequence are at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 97%, 98% or 99% identical over a region of 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 30, 35, 40, 45, 50 or more nucleotides or amino acids, or with respect to nucleic acids, if the first sequence is substantially complementary to the complement of the second sequence. r. Target “Target” as used herein may mean a polynucleotide that may be bound by one or more probes under stringent hybridization conditions. s. Terminator “Terminator” used herein may mean a sequence at the end of a transcriptional unit which signals termination of transcription. A terminator may be a 3′-non-translated DNA sequence containing a polyadenylation signal, which may facilitate the addition of polyadenylate sequences to the 3′-end of a primary transcript. A terminator may be derived from sources including viral, bacterial, fungal, plants, insects, and animals. Representative examples of terminators include the SV40 polyadenylation signal, HSV TK polyadenylation signal, CYC1 terminator, ADH terminator, SPA terminator, nopaline synthase (NOS) gene terminator of Agrobacterium tumefaciens, the terminator of the Cauliflower mosaic virus (CaMV) 35S gene, the zein gene terminator from Zea mays, the Rubisco small subunit gene (SSU) gene terminator sequences, subclover stunt virus (SCSV) gene sequence terminators, rho-independent E. coli terminators, and the lacZ alpha terminator. t. Vector “Vector” used herein may mean a nucleic acid sequence containing an origin of replication. A vector may be a plasmid, bacteriophage, bacterial artificial chromosome or yeast artificial chromosome. A vector may be a DNA or RNA vector. A vector may be either a self-replicating extrachromosomal vector or a vector which integrate into a host genome. 2. MicroRNA While not being bound by theory, the current model for the maturation of mammalian miRNAs is shown in FIG. 1. A gene coding for a miRNA may be transcribed leading to production of an miRNA precursor known as the pri-miRNA. The pri-miRNA may be part of a polycistronic RNA comprising multiple pri-miRNAs. The pri-miRNA may form a hairpin with a stem and loop. As indicated on FIG. 1, the stem may comprise mismatched bases. The hairpin structure of the pri-miRNA may be recognized by Drosha, which is an RNase III endonuclease. Drosha may recognize terminal loops in the pri-miRNA and cleave approximately two helical turns into the stem to produce a 60-70 nt precursor known as the pre-miRNA. Drosha may cleave the pri-miRNA with a staggered cut typical of RNase III endonucleases yielding a pre-miRNA stem loop with a 5′ phosphate and ˜2 nucleotide 3′ overhang. Approximately one helical turn of stem (˜10 nucleotides) extending beyond the Drosha cleavage site may be essential for efficient processing. The pre-miRNA may then be actively transported from the nucleus to the cytoplasm by Ran-GTP and the export receptor Ex-portin-5. The pre-miRNA may be recognized by Dicer, which is also an RNase III endonuclease. Dicer may recognize the double-stranded stem of the pre-miRNA. Dicer may also recognize the 5′ phosphate and 3′ overhang at the base of the stem loop. Dicer may cleave off the terminal loop two helical turns away from the base of the stem loop leaving an additional 5′ phosphate and ˜2 nucleotide 3′ overhang. The resulting siRNA-like duplex, which may comprise mismatches, comprises the mature miRNA and a similar-sized fragment known as the miRNA*. The miRNA and miRNA* may be derived from opposing arms of the pri-miRNA and pre-miRNA. MiRNA* sequences may be found in libraries of cloned miRNAs but typically at lower frequency than the miRNAs. Although initially present as a double-stranded species with miRNA*, the miRNA may eventually become incorporated as single-stranded RNAs into a ribonucleoprotein complex known as the RNA-induced silencing complex (RISC). Various proteins can form the RISC, which can lead to variability in specifity for miRNA/miRNA* duplexes, binding site of the target gene, activity of miRNA (repress or activate), which strand of the miRNA/miRNA* duplex is loaded in to the RISC. When the miRNA strand of the miRNA:miRNA* duplex is loaded into the RISC, the miRNA* may be removed and degraded. The strand of the miRNA:miRNA* duplex that is loaded into the RISC may be the strand whose 5′ end is less tightly paired. In cases where both ends of the miRNA:miRNA* have roughly equivalent 5′ pairing, both miRNA and miRNA* may have gene silencing activity. The RISC may identify target nucleic acids based on high levels of complementarity between the miRNA and the mRNA, especially by nucleotides 2-8 of the miRNA. Only one case has been reported in animals where the interaction between the miRNA and its target was along the entire length of the miRNA. This was shown for mir-196 and Hox B8 and it was further shown that mir-196 mediates the cleavage of the Hox B8 mRNA (Yekta et al 2004, Science 304-594). Otherwise, such interactions are known only in plants (Bartel & Bartel 2003, Plant Physiol 132-709). A number of studies have looked at the base-pairing requirement between miRNA and its mRNA target for achieving efficient inhibition of translation (reviewed by Bartel 2004, Cell 116-281). In mammalian cells, the first 8 nucleotides of the miRNA may be important (Doench & Sharp 2004 GenesDev 2004-504). However, other parts of the microRNA may also participate in mRNA binding. Moreover, sufficient base pairing at the 3′ can compensate for insufficient pairing at the 5′ (Brennecke at al, 2005 PLoS 3-e85). Computation studies, analyzing miRNA binding on whole genomes have suggested a specific role for bases 2-7 at the 5′ of the miRNA in target binding but the role of the first nucleotide, found usually to be “A” was also recognized (Lewis et at 2005 Cell 120-15). Similarly, nucleotides 1-7 or 2-8 were used to identify and validate targets by Krek et al (2005, Nat Genet 37-495). The target sites in the mRNA may be in the 5′ UTR, the 3′ UTR or in the coding region. Interestingly, multiple miRNAs may regulate the same mRNA target by recognizing the same or multiple sites. The presence of multiple miRNA complementarity sites in most genetically identified targets may indicate that the cooperative action of multiple RISCs provides the most efficient translational inhibition. MiRNAs may direct the RISC to downregulate gene expression by either of two mechanisms: mRNA cleavage or translational repression. The miRNA may specify cleavage of the mRNA if the mRNA has a certain degree of complementarity to the miRNA. When a miRNA guides cleavage, the cut may be between the nucleotides pairing to residues 10 and 11 of the miRNA. Alternatively, the miRNA may repress translation if the miRNA does not have the requisite degree of complementarity to the miRNA. Translational repression may be more prevalent in animals since animals may have a lower degree of complementarity. It should be notes that there may be variability in the 5′ and 3′ ends of any pair of miRNA and miRNA*. This variability may be due to variability in the enzymatic processing of Drosha and Dicer with respect to the site of cleavage. Variability at the 5′ and 3′ ends of miRNA and miRNA* may also be due to mismatches in the stem structures of the pri-miRNA and pre-miRNA. The mismatches of the stem strands may lead to a population of different hairpin structures. Variability in the stem structures may also lead to variability in the products of cleavage by Drosha and Dicer. 3. Nucleic Acid The present invention relates to an isolated nucleic acid comprising a nucleotide sequence referred to in SEQ ID NOS: 1-760616, the sequences set forth on the Sequence Listing of U.S. patent application Ser. No. 10/709,572, the contents of which are incorporated herein by reference, and the sequences set forth on the Sequence Listing of U.S. Provisional Patent Application No. 60/655,094, the contents of which are incorporated herein by reference, or variants thereof. The variant may be a complement of the referenced nucleotide sequence. The variant may also be a nucleotide sequence that is substantially identical to the referenced nucleotide sequence or the complement thereof. The variant may also be a nucleotide sequence which hybridizes under stringent conditions to the referenced nucleotide sequence, complements thereof, or nucleotide sequences substantially identical thereto. The nucleic acid may have a length of from 10 to 100 nucleotides. The nucleic acid may have a length of at least 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 35, 40, 45, 50, 60, 70, 80 or 90 nucleotides. The nucleic acid may be synthesized or expressed in a cell (in vitro or in vivo) using a synthetic gene described below. The nucleic acid may be synthesized as a single strand molecule and hybridized to a substantially complementary nucleic acid to form a duplex, which is considered a nucleic acid of the invention. The nucleic acid may be introduced to a cell, tissue or organ in a single- or double-stranded form or capable of being expressed by a synthetic gene using methods well known to those skilled in the art, including as described in U.S. Pat. No. 6,506,559 which is incorporated by reference. a. Pri-MiRNA The nucleic acid of the invention may comprise a sequence of a pri-miRNA or a variant thereof. The pri-miRNA sequence may comprise from 45-250, 55-200, 70-150 or 80-100 nucleotides. The sequence of the pri-miRNA may comprise a pre-miRNA, miRNA and miRNA* as set forth below. The pri-miRNA may also comprise a miRNA or miRNA* and the complement thereof, and variants thereof. The pri-miRNA may comprise at least 19% adenosine nucleotides, at least 16% cytosine nucleotides, at least 23% thymine nucleotides and at least 19% guanine nucleotides. The pri-miRNA may form a hairpin structure. The hairpin may comprise a first and second nucleic acid sequence that are substantially complimentary. The first and second nucleic acid sequence may be from 37-50 nucleotides. The first and second nucleic acid sequence may be separated by a third sequence of from 8-12 nucleotides. The hairpin structure may have a free energy less than −25 Kcal/mole as calculated by the Vienna algorithm with default parameters, as described in Hofacker et al., Monatshefte f. Chemie 125: 167-188 (1994), the contents of which are incorporated herein. The hairpin may comprise a terminal loop of 4-20, 8-12 or 10 nucleotides. The sequence of the pri-miRNA may comprise the sequence of a hairpin referred to in Table 1, the sequence of sequence identifiers 6757248-6894882 of the Sequence Listing of U.S. patent application Ser. No. 10/709,572, the contents of which are incorporated herein by reference, the sequence of sequence identifiers 1-6318 or 18728-18960 of the Sequence Listing of U.S. Provisional Patent Application No. 60/655,094, the contents of which are incorporated herein by reference, or variants thereof. b. Pre-MiRNA The nucleic acid of the invention may also comprise a sequence of a pre-miRNA or a variant thereof. The pre-miRNA sequence may comprise from 45-90, 60-80 or 60-70 nucleotides. The sequence of the pre-miRNA may comprise a miRNA and a miRNA* as set forth below. The pre-miRNA may also comprise a miRNA or miRNA* and the complement thereof, and variants thereof. The sequence of the pre-miRNA may also be that of a pri-miRNA excluding from 0-160 nucleotides from the 5′ and 3′ ends of the pri-miRNA. The sequence of the pre-miRNA may comprise the sequence of a hairpin referred to in Table 1, the sequence of sequence identifiers 6757248-6894882 of the Sequence Listing of U.S. patent application Ser. No. 10/709,572, the contents of which are incorporated herein by reference, the sequence of sequence identifiers 1-6318 or 18728-18960 of the Sequence Listing of U.S. Provisional Patent Application No. 60/655,094, the contents of which are incorporated herein by reference, or variants thereof. c. MiRNA The nucleic acid of the invention may also comprise a sequence of a miRNA, miRNA* or a variant thereof. The miRNA sequence may comprise from 13-33, 18-24 or 21-23 nucleotides. The sequence of the miRNA may be the first 13-33 nucleotides of the pre-miRNA. The sequence of the miRNA may be the last 13-33 nucleotides of the pre-miRNA. The sequence of the miRNA may comprise the sequence of a miRNA referred to in Table 1, the sequence of sequence identifiers 1-117750 or 6894883-10068177 of the Sequence Listing of U.S. patent application Ser. No. 10/709,572, the contents of which are incorporated herein by reference, the sequence of sequence identifiers 6319-18727 or 18961-19401 of the Sequence Listing of U.S. Provisional Patent Application No. 60/655,094, the contents of which are incorporated herein by reference, or variants thereof. d. Anti-MiRNA The nucleic acid of the invention may also comprise a sequence of an anti-miRNA that is capable of blocking the activity of a miRNA or miRNA*. The anti-miRNA may comprise a total of 5-100 or 10-60 nucleotides. The anti-miRNA may also comprise a total of at least 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25 or 26 nucleotides. The sequence of the anti-miRNA may comprise (a) at least 5 nucleotides that are substantially identical to the 5′ of a miRNA and at least 5-12 nucleotide that are substantially complimentary to the flanking regions of the target site from the 5′ end of said miRNA, or (b) at least 5-12 nucleotides that are substantially identical to the 3′ of a miRNA and at least 5 nucleotide that are substantially complimentary to the flanking region of the target site from the 3′ end of said miRNA. The sequence of the anti-miRNA may comprise the compliment of a sequence of a miRNA referred to in Table 1, the sequence of sequence identifiers 1-117750 or 6894883-10068177 of the Sequence Listing of U.S. patent application Ser. No. 10/709,572, the contents of which are incorporated herein by reference, the sequence of sequence identifiers 6319-18727 or 18961-19401 of the Sequence Listing of U.S. Provisional Patent Application No. 60/655,094, the contents of which are incorporated herein by reference, or variants thereof. e. Binding Site of Target The nucleic acid of the invention may also comprise a sequence of a target miRNA binding site, or a variant thereof. The target site sequence may comprise a total of 5-100 or 10-60 nucleotides. The target site sequence may comprise at least 5 nucleotides of the sequence of a target gene binding site referred to in Table 4, the sequence of sequence identifiers 117751-6757247 of the Sequence Listing of U.S. patent application Ser. No. 10/709,572, the contents of which are incorporated herein by reference, or variants thereof. 4. Synthetic Gene The present invention also relates to a synthetic gene comprising a nucleic acid of the invention operably linked to a transcriptional and/or translational regulatory sequences. The synthetic gene may be capable of modifying the expression of a target gene with a binding site for the nucleic acid of the invention. Expression of the target gene may be modified in a cell, tissue or organ. The synthetic gene may be synthesized or derived from naturally-occurring genes by standard recombinant techniques. The synthetic gene may also comprise terminators at the 3′-end of the transcriptional unit of the synthetic gene sequence. The synthetic gene may also comprise a selectable marker. 5. Vector The present invention also relates to a vector comprising a synthetic gene of the invention. The vector may be an expression vector. An expression vector may comprise additional elements. For example, the expression vector may have two replication systems allowing it to be maintained in two organisms, e.g., in mammalian or insect cells for expression and in a prokaryotic host for cloning and amplification. For integrating expression vectors, the expression vector may contain at least one sequence homologous to the host cell genome, and preferably two homologous sequences which flank the expression construct. The integrating vector may be directed to a specific locus in the host cell by selecting the appropriate homologous sequence for inclusion in the vector. The vector may also comprise a selectable marker gene to allow the selection of transformed host cells. 6. Host Cell The present invention also relates to a host cell comprising a vector of the invention. The cell may be a bacterial, fungal, plant, insect or animal cell. 7. Probes The present invention also relates to a probe comprising a nucleic acid of the invention. Probes may be used for screening and diagnostic methods, as outlined below. The probe may be attached or immobilized to a solid substrate, such as a biochip. The probe may have a length of from 8 to 500, 10 to 100 or 20 to 60 nucleotides. The probe may also have a length of at least 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 35, 40, 45, 50, 60, 70, 80, 90, 100, 120, 140, 160, 180, 200, 220, 240, 260, 280 or 300 nucleotides. The probe may further comprise a linker sequence of from 10-60 nucleotides. 8. Biochip The present invention also relates to a biochip. The biochip may comprise a solid substrate comprising an attached probe or plurality of probes of the invention. The probes may be capable of hybridizing to a target sequence under stringent hybridization conditions. The probes may be attached at spatially defined address on the substrate. More than one probe per target sequence may be used, with either overlapping probes or probes to different sections of a particular target sequence. The probes may be capable of hybridizing to target sequences associated with a single disorder. The probes may be attached to the biochip in a wide variety of ways, as will be appreciated by those in the art. The probes may either be synthesized first, with subsequent attachment to the biochip, or may be directly synthesized on the biochip. The solid substrate may be a material that may be modified to contain discrete individual sites appropriate for the attachment or association of the probes and is amenable to at least one detection method. Representative examples of substrates include glass and modified or functionalized glass, plastics (including acrylics, polystyrene and copolymers of styrene and other materials, polypropylene, polyethylene, polybutylene, polyurethanes, TeflonJ, etc.), polysaccharides, nylon or nitrocellulose, resins, silica or silica-based materials including silicon and modified silicon, carbon, metals, inorganic glasses and plastics. The substrates may allow optical detection without appreciably fluorescing. The substrate may be planar, although other configurations of substrates may be used as well. For example, probes may be placed on the inside surface of a tube, for flow-through sample analysis to minimize sample volume. Similarly, the substrate may be flexible, such as a flexible foam, including closed cell foams made of particular plastics. The biochip and the probe may be derivatized with chemical functional groups for subsequent attachment of the two. For example, the biochip may be derivatized with a chemical functional group including, but not limited to, amino groups, carboxyl groups, oxo groups or thiol groups. Using these functional groups, the probes may be attached using functional groups on the probes either directly or indirectly using a linkers. The probes may be attached to the solid support by either the 5′ terminus, 3′ terminus, or via an internal nucleotide. The probe may also be attached to the solid support non-covalently. For example, biotinylated oligonucleotides can be made, which may bind to surfaces covalently coated with streptavidin, resulting in attachment. Alternatively, probes may be synthesized on the surface using techniques such as photopolymerization and photolithography. 9. MiRNA Expression Analysis The present invention also relates to a method of identifying miRNAs that are associated with disease or a pathological condition comprising contacting a biological sample with a probe or biochip of the invention and detecting the amount of hybridization. PCR may be used to amplify nucleic acids in the sample, which may provide higher sensitivity. The ability to identify miRNAs that are overexpressed or underexpressed in pathological cells compared to a control can provide high-resolution, high-sensitivity datasets which may be used in the areas of diagnostics, therapeutics, drug development, pharmacogenetics, biosensor development, and other related areas. An expression profile generated by the current methods may be a “fingerprint” of the state of the sample with respect to a number of miRNAs. While two states may have any particular miRNA similarly expressed, the evaluation of a number of miRNAs simultaneously allows the generation of a gene expression profile that is characteristic of the state of the cell. That is, normal tissue may be distinguished from diseased tissue. By comparing expression profiles of tissue in known different disease states, information regarding which miRNAs are associated in each of these states may be obtained. Then, diagnosis may be performed or confirmed to determine whether a tissue sample has the expression profile of normal or disease tissue. This may provide for molecular diagnosis of related conditions. 10. Determining Expression Levels The present invention also relates to a method of determining the expression level of a disease-associated miRNA comprising contacting a biological sample with a probe or biochip of the invention and measuring the amount of hybridization. The expression level of a disease-associated miRNA is information in a number of ways. For example, a differential expression of a disease-associated miRNA compared to a control may be used as a diagnostic that a patient suffers from the disease. Expression levels of a disease-associated miRNA may also be used to monitor the treatment and disease state of a patient. Furthermore, expression levels of e disease-associated miRNA may allow the screening of drug candidates for altering a particular expression profile or suppressing an expression profile associated with disease. A target nucleic acid may be detected by contacting a sample comprising the target nucleic acid with a biochip comprising an attached probe sufficiently complementary to the target nucleic acid and detecting hybridization to the probe above control levels. The target nucleic acid may also be detected by immobilizing the nucleic acid to be examined on a solid support such as nylon membranes and hybridizing a labelled probe with the sample. Similarly, the target nucleic may also be detected by immobilizing the labeled probe to the solid support and hybridizing a sample comprising a labeled target nucleic acid. Following washing to remove the non-specific hybridization, the label may be detected. The target nucleic acid may also be detected in situ by contacting permeabilized cells or tissue samples with a labeled probe to allow hybridization with the target nucleic acid. Following washing to remove the non-specifically bound probe, the label may be detected. These assays can be direct hybridization assays or can comprise sandwich assays, which include the use of multiple probes, as is generally outlined in U.S. Pat. Nos. 5,681,702; 5,597,909; 5,545,730; 5,594,117; 5,591,584; 5,571,670; 5,580,731; 5,571,670; 5,591,584; 5,624,802; 5,635,352; 5,594,118; 5,359,100; 5,124,246; and 5,681,697, each of which is hereby incorporated by reference. A variety of hybridization conditions may be used, including high, moderate and low stringency conditions as outlined above. The assays may be performed under stringency conditions which allow hybridization of the probe only to the target. Stringency can be controlled by altering a step parameter that is a thermodynamic variable, including, but not limited to, temperature, formamide concentration, salt concentration, chaotropic salt concentration pH, or organic solvent concentration. Hybridization reactions may be accomplished in a variety of ways. Components of the reaction may be added simultaneously, or sequentially, in different orders. In addition, the reaction may include a variety of other reagents. These include salts, buffers, neutral proteins, e.g., albumin, detergents, etc. which may be used to facilitate optimal hybridization and detection, and/or reduce non-specific or background interactions. Reagents that otherwise improve the efficiency of the assay, such as protease inhibitors, nuclease inhibitors and anti-microbial agents may also be used as appropriate, depending on the sample preparation methods and purity of the target. a. Diagnostic The present invention also relates to a method of diagnosis comprising detecting a differential expression level of a disease-associated miRNA in a biological sample. The sample may be derived from a patient. Diagnosis of a disease state in a patient allows for prognosis and selection of therapeutic strategy. Further, the developmental stage of cells may be classified by determining temporarily expressed miRNA-molecules. In situ hybridization of labeled probes to tissue arrays may be performed. When comparing the fingerprints between an individual and a standard, the skilled artisan can make a diagnosis, a prognosis, or a prediction based on the findings. It is further understood that the genes which indicate the diagnosis may differ from those which indicate the prognosis and molecular profiling of the condition of the cells may lead to distinctions between responsive or refractory conditions or may be predictive of outcomes. b. Drug Screening The present invention also relates to a method of screening therapeutics comprising contacting a pathological cell capable of expressing a disease related miRNA with a candidate therapeutic and evaluating the effect of a drug candidate on the expression profile of the disease associated miRNA. Having identified the differentially expressed miRNAs, a variety of assays may be executed. Test compounds may be screened for the ability to modulate gene expression of the disease associated miRNA. Modulation includes both an increase and a decrease in gene expression. The test compound or drug candidate may be any molecule, e.g., protein, oligopeptide, small organic molecule, polysaccharide, polynucleotide, etc., to be tested for the capacity to directly or indirectly alter the disease phenotype or the expression of the disease associated miRNA. Drug candidates encompass numerous chemical classes, such as small organic molecules having a molecular weight of more than 100 and less than about 500, 1,000, 1,500, 2,000 or 2,500 daltons. Candidate compounds may comprise functional groups necessary for structural interaction with proteins, particularly hydrogen bonding, and typically include at least an amine, carbonyl, hydroxyl or carboxyl group, preferably at least two of the functional chemical groups. The candidate agents may comprise cyclical carbon or heterocyclic structures and/or aromatic or polyaromatic structures substituted with one or more of the above functional groups. Candidate agents are also found among biomolecules including peptides, saccharides, fatty acids, steroids, purines, pyrimidines, derivatives, structural analogs or combinations thereof. Combinatorial libraries of potential modulators may be screened for the ability to bind to the disease associated miRNA or to modulate the activity thereof. The combinatorial library may be a collection of diverse chemical compounds generated by either chemical synthesis or biological synthesis by combining a number of chemical building blocks such as reagents. Preparation and screening of combinatorial chemical libraries is well known to those of skill in the art. Such combinatorial chemical libraries include, but are not limited to, peptide libraries encoded peptides, benzodiazepines, diversomers such as hydantoins, benzodiazepines and dipeptide, vinylogous polypeptides, analogous organic syntheses of small compound libraries, oligocarbamates, and/or peptidyl phosphonates, nucleic acid libraries, peptide nucleic acid libraries, antibody libraries, carbohydrate libraries, and small organic molecule libraries. 11. Gene Silencing The present invention also relates to a method of using the nucleic acids of the invention to reduce expression of a target gene in a cell, tissue or organ. Expression of the target gene may be reduced by expressing a nucleic acid of the invention that comprises a sequence substantially complementary to one or more binding sites of the target mRNA. The nucleic acid may be a miRNA or a variant thereof. The nucleic acid may also be pri-miRNA, pre-miRNA, or a variant thereof, which may be processed to yield a miRNA. The expressed miRNA may hybridize to a substantially complementary binding site on the target mRNA, which may lead to activation of RISC-mediated gene silencing. An example for a study employing over-expression of miRNA is Yekta et al 2004, Science 304-594, which is incorporated herein by reference. One of ordinary skill in the art will recognize that the nucleic acids of the present invention may be used to inhibit expression of target genes using antisense methods well known in the art, as well as RNAi methods described in U.S. Pat. Nos. 6,506,559 and 6,573,099, which are incorporated by reference. The target of gene silencing may be a protein that causes the silencing of a second protein. By repressing expression of the target gene, expression of the second protein may be increased. Examples for efficient suppression of miRNA expression are the studies by Esau et al 2004 JBC 275-52361; and Cheng et al 2005 Nucleic Acids Res. 33-1290, which is incorporated herein by reference. 12. Gene Enhancement The present invention also relates to a method of using the nucleic acids of the invention to increase expression of a target gene in a cell, tissue or organ. Expression of the target gene may be increased by expressing a nucleic acid of the invention that comprises a sequence substantially complementary to a pri-miRNA, pre-miRNA, miRNA or a variant thereof. The nucleic acid may be an anti-miRNA. The anti-miRNA may hybridize with a pri-miRNA, pre-miRNA or miRNA, thereby reducing its gene repression activity. Expression of the target gene may also be increased by expressing a nucleic acid of the invention that is substantially complementary to a portion of the binding site in the target gene, such that binding of the nucleic acid to the binding site may prevent miRNA binding. 13. Therapeutic The present invention also relates to a method of using the nucleic acids of the invention as modulators or targets of disease or disorders associated with developmental dysfunctions, such as cancer. In general, the claimed nucleic acid molecules may be used as a modulator of the expression of genes which are at least partially complementary to said nucleic acid. Further, miRNA molecules may act as target for therapeutic screening procedures, e.g. inhibition or activation of miRNA molecules might modulate a cellular differentiation process, e.g. apoptosis. Furthermore, existing miRNA molecules may be used as starting materials for the manufacture of sequence-modified miRNA molecules, in order to modify the target-specificity thereof, e.g. an oncogene, a multidrug-resistance gene or another therapeutic target gene. Further, miRNA molecules can be modified, in order that they are processed and then generated as double-stranded siRNAs which are again directed against therapeutically relevant targets. Furthermore, miRNA molecules may be used for tissue reprogramming procedures, e.g. a differentiated cell line might be transformed by expression of miRNA molecules into a different cell type or a stem cell. 14. Compositions The present invention also relates to a pharmaceutical composition comprising the nucleic acids of the invention and optionally a pharmaceutically acceptable carrier. The compositions may be used for diagnostic or therapeutic applications. The administration of the pharmaceutical composition may be carried out by known methods, wherein a nucleic acid is introduced into a desired target cell in vitro or in vivo. Commonly used gene transfer techniques include calcium phosphate, DEAE-dextran, electroporation, microinjection, viral methods and cationic liposomes. 15. Kits The present invention also relates to kits comprising a nucleic acid of the invention together with any or all of the following: assay reagents, buffers, probes and/or primers, and sterile saline or another pharmaceutically acceptable emulsion and suspension base. In addition, the kits may include instructional materials containing directions (e.g., protocols) for the practice of the methods of this invention. EXAMPLE 1 Prediction Of MiRNAs We surveyed the entire human genome for potential miRNA coding genes using two computational approaches similar to those described in U.S. Patent Application No. 60/522,459, Ser. Nos. 10/709,577 and 10/709,572, the contents of which are incorporated herein by reference, for predicting miRNAs. Briefly, non-protein coding regions of the entire human genome were scanned for hairpin structures. The predicted hairpins and potential miRNAs were scored by thermodynamic stability, as well as structural and contextual features. The algorithm was calibrated by using miRNAs in the Sanger Database which had been validated. 1. First Screen Table 2 of U.S. patent application Ser. No. 10/709,572, the contents of which are incorporated herein by reference, shows the sequence (“PRECURSOR SEQUENCE”), sequence identifier (“PRECUR SEQ-ID”) and organism of origin (“GAM ORGANISM”) for each predicted hairpin from the first computational screen, together with the predicted miRNAs (“GAM NAME”). Table 1 of U.S. patent application Ser. No. 10/709,572, the contents of which are incorporated herein by reference, shows the sequence (“GAM RNA SEQUENCE”) and sequence identifier (“GAM SEQ-ID”) for each miRNA (“GAM NAME”), along with the organism of origin (“GAM ORGANISM”) and Dicer cut location (“GAM POS”). The sequences of the predicted hairpins and miRNA are also set forth on the Sequence Listing of U.S. patent application Ser. No. 10/709,572, the contents of which are incorporated herein by reference. 2. Second Screen Table 1 lists the SEQ ID NO for each predicted hairpin (“HID”) of the second computational screen. Table 1 also lists the genomic location for each hairpin (“Hairpin Location”). The format for the genomic location is a concatenation of <chr_id><strand><start position>. For example, 19+135460000 refers chromosome 19, +strand, start position 135460000. Chromosomes 23-25 refer to chromosome X, chromosome Y and mitochondrial DNA. The chromosomal location is based on the hg17 assembly of the human genome by UCSC (http://genome.ucsc.edu), which is based on NCBI Build 35 version 1 and was produced by the International Human Genome Sequencing Consortium. Table 1 also lists whether the hairpin is conserved in evolution (“C”). There is an option that there is a paper of the genome version. The hairpins were identified as conserved (“Y”) or nonconserved (“N”) by using phastCons data. The phastCons data is a measure of evolutionary conservation for each nucleotide in the human genome against the genomes of chimp, mouse, rat, dog, chicken, frog, and zebrafish, based on a phylo-HMM using best-in-genome pair wise alignment for each species based on BlastZ, followed by multiZ alignment of the 8 genomes (Siepel et al, J. Comput. Biol 11, 413-428, 2004 and Schwartz et al., Genome Res. 13, 103-107, 2003). A hairpin is listed as conserved if the average phastCons conservation score over the 7 species in any 15 nucleotide sequence within the hairpin stem is at least 0.9 (Berezikov, E. et al. Phylogenetic Shadowing and Computational Identification of Human microRNA Genes. Cell 120, 21-24, 2005). Table 1 also lists the genomic type for each hairpin (“T”) as either intergenic (“G”), intron (“I”) or exon (“E”). Table 1 also lists the SEQ ID NO (“MID”) for each predicted miRNA and miRNA*. Table 1 also lists the prediction score grade for each hairpin (“P”) on a scale of 0-1 (1 the hairpin is the most reliable), as described in Hofacker et al., Monatshefte f. Chemie 125: 167-188, 1994. If the grade is zero or null, they are transformed to the lower value of PalGrade that its p-value is <0.05. Table 1 also lists the p-value (“Pval”) calculated out of background hairpins for the values of each P scores. As shown in Table, there are few instances where the Pval is >0.05. In each of these cases, the hairpins are highly conserved or they have been validated (F=Y). Table 1 also lists whether the miRNAs were validated by expression analysis (“E”) (Y=Yes, N=No), as detailed in Table 2. Table 1 also lists whether the miRNAs were validated by sequencing (“S”) (Y=Yes, N=No). If there was a difference in sequences between the predicted and sequenced miRNAs, the sequenced sequence is predicted. It should be noted that failure to sequence or detect expression of a miRNA does not necessarily mean that a miRNA does not exist. Such undetected miRNAs may be expressed in tissues other than those tested. In addition, such undetected miRNAs may be expressed in the test tissues, but at a difference stage or under different condition than those of the experimental cells. Table 1 also listed whether the miRNAs were shown to be differentially expressed (“D”) (Y=Yes, N=No) in at least one disease, as detailed in Table 2). Table 1 also whether the miRNAs were present (“F”) (Y=Yes, N=No) in Sanger DB Release 6.0 (April 2005) (http://nar.oupjournals.org/) as being detected in humans or mice or predicted in humans. As discussed above, the miRNAs listed in the Sanger database are a component of the prediction algorithm and a control for the output. Table 1 also lists a genetic location cluster (“LC”) for those hairpins that are within 5,000 nucleotides of each other. Each miRNA that has the same LC share the same genetic cluster. Table 1 also lists a seed cluster (“SC”) to group miRNAs by their seed of 2-7 by an exact match. Each miRNA that has the same SC have the same seed. For a discussion of seed lengths of 5 nucleotides, see Lewis et al., Cell, 120; 15-20 (2005). EXAMPLE 2 Prediction of Target Genes The predicted miRNAs from the two computational screens of Example 1 were then used to predict target genes and their binding sites using two computational approaches similar to those described in U.S. Patent Application No. 60/522,459, Ser. Nos. 10/709,577 and 10/709,572, the contents of which are incorporated herein by reference, for predicting miRNAs. 1. First Screen Table 6 of U.S. patent application Ser. No. 10/709,572, the contents of which are incorporated herein by reference, lists the predicted target genes (“TARGET”) and binding site sequence (“TARGET BINDING SITE SEQUENCE”) and binding site sequence identifier (“TARGET BINDING SITE SEQ-ID”) from the first computational screen, as well as the organism of origin for the target (“TARGET ORGANISM”). Table 12 of U.S. patent application Ser. No. 10/709,572, the contents of which are incorporated herein by reference, lists the diseases (“DISEASE NAME”) that are associated with the target genes (“TARGET-GENES ASSOCIATED WITH DISEASE”). Table 14 of U.S. patent application Ser. No. 10/709,572, the contents of which are incorporated herein by reference, lists the sequence identifiers for the miRNAs (“SEQ ID NOs OF GAMS ASSOCIATED WITH DISEASE”) and the diseases (“DISEASE NAME”) that are associated with the miRNA based on the target gene. The sequences of the binding site sequences are also set forth on the Sequence Listing of U.S. patent application Ser. No. 10/709,572, the contents of which are incorporated herein by reference. 2. Second Screen Table 4 lists the predicted target gene for each miRNA (MID) and its hairpin (HID) from the second computational screen. The names of the target genes were taken from NCBI Reference Sequence release 9 (http://www.ncbi.nlm.nih.gov; Pruitt et al., Nucleic Acids Res, 33(1):D501-D504, 2005; Pruitt et al., Trends Genet., 16(1):44-47, 2000; and Tatusova et al., Bioinformatics, 15(7-8):536-43, 1999). Target genes were identified by having a perfect complimentary match of a 7 nucleotide miRNA seed (positions 2-8) and an A on the UTR (total=8 nucleotides). For a discussion on identifying target genes, see Lewis et al., Cell, 120: 15-20, (2005). For a discussion of the seed being sufficient for binding of a miRNA to a UTR, see Lim Lau et al., (Nature 2005) and Brenneck et al, (PLOS Biol 2005). Binding sites were then predicted using a filtered target genes dataset by including only those target genes that contained a UTR of a least 30 nucleotides. The binding site screen only considered the first 4000 nucleotides per UTR and considered the longest transcript when there were several transcripts per gene. The filtering reduced the total number of transcripts from 23626 to 14239. Table 4 lists the SEQ ID NO for the predicted binding sites for each target gene. The sequence of the binding site includes the 20 nucleotides 5′ and 3′ of the binding site as they are located on the spliced mRNA. Except for those miRNAs that have only a single predicted binding site or those miRNAs that were validated, the data in Table 4 has been filtered to only indicate those target genes with at least 2 binding sites. Table 5 shows the relationship between the miRNAs (“MID”)/hairpins (“HID”) and diseases by their target genes. The name of diseases are taken from OMIM. For a discussion of the rational for connecting the host gene the hairpin is located upon to disease, see Baskerville and Bartel, RNA, 11: 241-247 (2005) and Rodriguez et al., Genome Res., 14: 1902-1910 (2004). Table 5 shows the number of miRNA target genes (“N”) that are related to the disease. Table 5 also shows the total number of genes that are related to the disease (“T”), which is taken from the genes that were predicted to have binding sites for miRNAs. Table 5 also shows the percentage of N out of T and the p-value of hypergeometric analysis (“Pval”). Table 8 shows the disease codes for Tables 5 and 6. For a reference of hypergeometric analysis, see Schaum's Outline of Elements of Statistics II: Inferential Statistics. Table 6 shows the relationship between the miRNAs (“MID”)/hairpins (“HID”) and diseases by their host genes. We defined hairpins genes on the complementary strand of a host gene as located on the gene: Intron_c as Interon and Exon_c as Exon. We choose the complementary strands as they can cause disease. For example, a mutation in the miRNA that is located on the complementary strand. In those case that a miRNA in on both strands, two statuses like when Intron and Exon_c Intron is the one chosen. The logic of choosing is Intron>Exon>Intron_c>Exon_c>Intergenic. Table 9 shows the relationship between the target sequences (“Gene Name”) and disease (“Disease Code”). EXAMPLE 3 Validation of MiRNAs 1. Expression Analysis—Set 1 To confirm the hairpins and miRNAs predicted in Example 1, we detected expression in various tissues using the high-throughput microarrays similar to those described in U.S. Patent Application No. 60/522,459, Ser. Nos. 10/709,577 and 10/709,572, the contents of which are incorporated herein by reference. For each predicted precursor miRNA, mature miRNAs derived from both stems of the hairpin were tested. Table 2 shows the hairpins (“HID”) of the second prediction set that were validated by detecting expression of related miRNAs (“MID”), as well as a code for the tissue (“Tissue”) that expression was detected. The tissue and diseases codes for Table 2 are listed in Table 7. Some of the tested tissues wee cell line. Lung carcinoma cell line (H1299) with/without P53: H1299 has a mutated P53. The cell line was transfected with a construct with P53 that is temperature sensitive (active at 32� C.). The experiment was conducted at 32� C. Table 2 also shows the chip expression score grade (range of 500-65000). A threshold of 500 was used to eliminate non-significant signals and the score was normalized by MirChip probe signals from different experiments. Variations in the intensities of fluorescence material between experiments may be due to variability in RNA preparation or labeling efficiency. We normalized based on the assumption that the total amount of miRNAs in each sample is relatively constant. First we subtracted the background signal from the raw signal of each probe, where the background signal is defined as 400. Next, we divided each miRNA probe signal by the average signal of all miRNAs, multiplied the result by 10000 and added back the background signal of 400. Thus, by definition, the sum of all miRNA probe signals in each experiment is 10400. Table 2 also shows a statistical analysis of the normalized signal (“Spval”) calculated on the normalized score. For each miRNA, we used a relevant control group out of the full predicted miRNA list. Each miRNA has an internal control of probes with mismatches. The relevant control group contained probes with similar C and G percentage (abs diff <5%) in order to have similar Tm. The probe signal P value is the ratio over the relevant control group probes with the same or higher signals. The results are p-value ≦0.05 and score is above 500. In those cases that the SPVal is listed as 0.0, the value is less than 0.0001. 2. Expression Analysis—Set 2 To further confirm the hairpins and miRNAs predicted in 0, we detected expression in additional tissues. Table 2 of U.S. Provisional Patent Application No. 60/655,094, which is incorporated herein by reference, lists expression data of miRNAs by the following: HID: hairpin sequence identifier for sequence set forth in the Sequence Listing of U.S. Provisional Patent Application No. 60/655,094, which is incorporated herein by reference; MID: miRNA sequence identifier for sequence set forth in the Sequence Listing of U.S. Provisional Patent Application No. 60/655,094, which is incorporated herein by reference; Tissue: tested tissue; S: chip expression score grade (range=100-65000); Dis. Diff. Exp.: disease related differential expression and the tissue it was tested in; R: ratio of disease related expression (range=0.01-99.99); and abbreviations: Brain Mix A—a mixture of brain tissue that are affected in Alzheimer; Brain Mix B—a mixture of all brain tissues; and Brain SN—Substantia Nigra. 3. Sequencing To further validate the hairpins (“HID”) of the second prediction, a number of miRNAs were validated by sequencing methods similar to those described in U.S. Patent Application No. 60/522,459, Ser. Nos. 10/709,577 and 10/709,572, the contents of which are incorporated herein by reference. Table 3 shows the hairpins (“HID”) that were validated by sequencing a miRNA (MID) in the indicated tissue (“Tissue”). EXAMPLE 4 MiRNAs of Chromosome 19 A group of the validated miRNAs from Example 3 were highly expressed in placenta, have distinct sequence similarity, and are located in the same locus on chromosome 19 (FIG. 2). These predicted miRNAs are spread along a region of ˜100,000 nucleotides in the 19q13.42 locus. This genomic region is devoid of protein-coding genes and seems to be intergenic. Further analysis of the genomic sequence, including a thorough examination of the output of our prediction algorithm, revealed many more putative related miRNAs, and located mir-371, mir-372, and mir-373 approximately 25,000 bp downstream to this region. Overall, 54 putative miRNA precursors were identified in this region. The miRNA precursors can be divided into four distinct types of related sequences (FIG. 2). About 75% of the miRNAs in the cluster are highly related and were labeled as type A. Three other miRNA types, types B, C and D, are composed of 4, 2, and 2 precursors, respectively. An additional 3 putative miRNA precursors (S1 to S3) have unrelated sequences. Interestingly, all miRNA precursors are in the same orientation as the neighboring mir-371, mir-372, and mir-373 miRNA precursors. Further sequence analysis revealed that the majority of the A-type miRNAs are embedded in a ˜600 bp region that is repeated 35 times in the cluster. The repeated sequence does not appear in other regions of the genome and is conserved only in primates. The repeating unit is almost always bounded by upstream and downstream Alu repeats. This is in sharp contrast to the MC14-1 cluster which is extremely poor in Alu repeats. FIG. 3-A shows a comparison of sequences of the 35 repeat units containing the A-type miRNA precursors in human. The comparison identified two regions exhibiting the highest sequence similarity. One region includes the A-type miRNA, located in the 3′ region of the repeat. The second region is located ˜100 nucleotides upstream to the A-type miRNA precursors. However, the second region does not show high similarity among the chimp repeat units while the region containing the A-type miRNA precursors does (FIG. 3-B). Examination of the region containing the A-type repeats showed that the 5′ region of the miRNAs encoded by the 5′ stem of the precursors (5p miRNAs) seem to be more variable than other regions of the mature miRNAs. This is matched by variability in the 3′ region of the mature miRNAs derived from the 3′ stems (3p miRNAs). As expected, the loop region is highly variable. The same phenomenon can also be observed in the multiple sequence alignment of all 43 A-type miRNAs (FIG. 4). The multiple sequence alignment presented in FIG. 4 revealed the following findings with regards to the predicted mature miRNAs. The 5p miRNAs can be divided into 3 blocks. Nucleotides 1 to 6 are C/T rich, relatively variable, and are marked in most miRNAs by a CTC motif in nucleotides 3 to 5. Nucleotides 7 to 15 are A/G rich and apart from nucleotides 7 and 8 are shared among most of the miRNAs. Nucleotides 16 to 23 are C/T rich and are, again, conserved among the members. The predicted 3p miRNAs, in general, show a higher conservation among the family members. Most start with an AAA motif, but a few have a different 5′ sequence that may be critical in their target recognition. Nucleotides 8 to 15 are C/T rich and show high conservation. The last 7 nucleotides are somewhat less conserved but include a GAG motif in nucleotides 17 to 19 that is common to most members. Analysis of the 5′ region of the repeated units identified potential hairpins. However, in most repeating units these hairpins were not preserved and efforts to clone miRNAs from the highest scoring hairpins failed. There are 8 A-type precursors that are not found within a long repeating unit. Sequences surrounding these precursors show no similarity to the A-type repeating units or to any other genomic sequence. For 5 of these A-type precursors there are Alu repeats located significantly closer downstream to the A-type sequence. The other miRNA types in the cluster showed the following characteristics. The four B group miRNAs are found in a repeated region of ˜500 bp, one of which is located at the end of the cluster. The two D-type miRNAs, which are ˜2000 nucleotides from each other, are located at the beginning of the cluster and are included in a duplicated region of 1220 nucleotides. Interestingly, the two D-type precursors are identical. Two of the three miRNAs of unrelated sequence, S1 and S2, are located just after the two D-type miRNAs, and the third is located between A34 and A35. In general, the entire ˜100,000 nucleotide region containing the cluster is covered with repeating elements. This includes the miRNA-containing repeating units that are specific to this region and the genome wide repeat elements that are spread in the cluster in large numbers. EXAMPLE 5 Cloning of Predicted MiRNAs To further validate the predicted miRNAs, a number of the miRNAs described in Example 4 were cloned using methods similar to those described in U.S. Patent Application No. 60/522,459, Ser. Nos. 10/709,577 and 10/709,572, the contents of which are incorporated herein by reference. Briefly, a specific capture oligonucleotide was designed for each of the predicted miRNAs. The oligonucleotide was used to capture, clone, and sequence the specific miRNA from a placenta-derived library enriched for small RNAs. We cloned 41 of the 43 A-type miRNAs, of which 13 miRNAs were not present on the original microarray but only computationally predicted, as well as the D-type miRNAs. For 11 of the predicted miRNA precursors, both 5p and 3p predicted mature miRNAs were present on the microarray and in all cases both gave significant signals. Thus, we attempted to clone both 5′ and 3′ mature miRNAs in all cloning attempts. For 27 of the 43 cloned miRNA, we were able to clone miRNA derived from both 5′ and 3′ stems. Since our cloning efforts were not exhaustive, it is possible that more of the miRNA precursors encode both 5′ and 3′ mature miRNAs. Many of the cloned miRNAs have shown heterogeneity at the 3′ end as observed in many miRNA cloning studies (Lagos-Quintana 2001, 2002, 2003) (Poy 2004). Interestingly, we also observed heterogeneity at the 5′ end for a significant number of the cloned miRNAs. This heterogeneity seemed to be somewhat more prevalent in 5′-stem derived miRNAs (9) compared to 3′-stem derived miRNAs (6). In comparison, heterogeneity at the 3′ end was similar for both 3′ and 5′-stem derived miRNAs (19 and 13, respectively). The 5′ heterogeneity involved mainly addition of one nucleotide, mostly C or A, but in one case there was an addition of 3 nucleotides. This phenomenon is not specific to the miRNAs in the chromosome 19 cluster. We have observed it for many additional cloned miRNAs, including both known miRNAs as well as novel miRNAs from other chromosomes (data not shown). EXAMPLE 6 Analysis Of MiRNA Expression To further examine the expression of the miRNAs of Example 4, we used Northern blot analysis to profile miRNA expression in several tissues. Northern blot analysis was performed using 40 μg of total RNA separated on 13% denaturing polyacrylamide gels and using 32P end labeled oligonucleotide probes. The oligonucleotide probe sequences were 5′-ACTCTAAAGAGAAGCGCTTTGT-3′ (A19-3p, NCBI: HSA-MIR-RG-21) and 5′-ACCCACCAAAGAGAAGCACTTT-3′ (A24-3p, NCBI: HSA-MIR-RG-27). The miRNAs were expressed as ˜22 nucleotide long RNA molecules with tissue specificity profile identical to that observed in the microarray analysis (FIG. 5-A). In order to determine how the MC19-1 cluster is transcribed. A survey of the ESTs in the region identified only one place that included ESTs with poly-adenylation signal and poly-A tail. This region is located just downstream to the A43 precursor. The only other region that had ESTs with poly-adenylation signal is located just after mir-373, suggesting that mir-371,2,3 are on a separate transcript. We performed initial studies focusing on the region around mir-A43 to ensure that the region is indeed transcribed into poly-adenylated mRNA. RT-PCR experiments using primers covering a region of 3.5 kb resulted in obtaining the expected fragment (FIG. 5-B). RT-PCR analysis was performed using 5 μg of placenta total RNA using oligo-dT as primer. The following primers were used to amplify the transcripts: f1: 5′-GTCCCTGTACTGGAACTTGAG-3′; f2: 5′-GTGTCCCTGTACTGGAACGCA-3′; r1: 5′-GCCTGGCCATGTCAGCTACG-3′; r2: 5′-TTGATGGGAGGCTAGTGTTTC-3′; r3: 5′-GACGTGGAGGCGTTCTTAGTC-3′; and r4: 5′-TGACAACCGTTGGGGATTAC-3′. The authenticity of the fragment was validated by sequencing. This region includes mir-A42 and mir-A43, which shows that both miRNAs are present on the same primary transcript. Further information on the transcription of the cluster came from analysis of the 77 ESTs located within it. We found that 42 of the ESTs were derived from placenta. As these ESTs are spread along the entire cluster, it suggested that the entire cluster is expressed in placenta. This observation is in-line with the expression profile observed in the microarray analysis. Thus, all miRNAs in the cluster may be co-expressed, with the only exception being the D-type miRNAs which are the only miRNAs to be expressed in HeLa cells. Interestingly, none of the 77 ESTs located in the region overlap the miRNA precursors in the cluster. This is in-line with the depletion of EST representation from transcripts processed by Drosha. Examination of the microarray expression profile revealed that miRNAs D1/2, A12, A21, A22, and A34, have a somewhat different expression profile reflected as low to medium expression levels in several of the other tissues examined. This may be explained by alternative splicing of the transcript(s) encoding the miRNAs or by the presence of additional promoter(s) of different tissues specificity along the cluster. Comparison of the expression of 3p and 5p mature miRNAs revealed that both are expressed for many miRNA precursors but in most cases at different levels. For most pre-miRNAs the 3p miRNAs are expressed at higher levels then the 5p miRNAs. However, in 6 cases (mir-D1,2, mir-A1, mir-A8, mir-A12, mir-A17 and mir-A33) both 3p and 5p miRNAs were expressed at a similar level, and in one case (mir-A32) the 5p miRNA was expressed at higher levels then the 3p miRNA. EXAMPLE 7 Conservation Comparison of the sequences from all four types of predicted miRNAs of Example 4 to that of other species (chimp, macaque, dog, chicken, mouse, rat, drosophila, zebra-fish, fungi, C. elegans) revealed that all miRNAs in the cluster, and in fact the entire region, are not conserved beyond primates. Interestingly, homologues of this region do not exist in any other genomes examined, including mouse and rat. Thus, this is the first miRNA cluster that is specific to primates and not generally shared in mammals. Homology analysis between chimp and human show that all 35 repeats carrying the A-type miRNAs are contiguous between the two species. Furthermore, the entire cluster seems to be identical between human and chimp. Thus, the multiple duplications leading to the emergence of the MC19-1 cluster must have occurred prior to the split of chimp and human and remained stable during the evolution of each species. It should be noted that human chromosome 19 is known to include many tandemly clustered gene families and large segmental duplications (Grimwood et al, 2004). Thus, in this respect the MC19-1 cluster is a natural part of chromosome 19. In comparison, the MC14-1 cluster is generally conserved in mouse and includes only the A7 and A8 miRNAs within the cluster are not conserved beyond primates (Seitz 2004). In contrast all miRNAs in the MC19-1 cluster are unique to primates. A survey of all miRNAs found in Sanger revealed that only three miRNA, mir-198, mir-373, and mir-422a, are not conserved in the mouse or rat genomes, however, they are conserved in the dog genome and are thus not specific to primates. Interestingly, mir-371 and mir-372, which are clustered with mir -373, and are located 25 kb downstream to the MC19-1 cluster, are homologous to some extent to the A-type miRNAs (FIG. 4), but are conserved in rodents. Comparison of the A-type miRNA sequences to the miRNAs in the Sanger database revealed the greatest homology to the human mir-302 family (FIG. 4-C). This homology is higher than the homology observed with mir-371,2,3. The mir-302 family (mir-302a, b, c, and d) are found in a tightly packed cluster of five miRNAs (including mir-367) covering 690 nucleotides located in the antisense orientation in the first intron within the protein coding exons of the HDCMA18P gene (accession NM—016648). No additional homology, apart from the miRNA homology, exists between the mir-302 cluster and the MC19-1 cluster. The fact that both the mir-371,2,3 and mir-302a,b,c,d are specific to embryonic stem cells is noteworthy. EXAMPLE 8 Differential Expression of MiRNAs Using chip expression methods similar to those described in 0, microarray images were analyzed using Feature Extraction Software (Version 7.1.1, Agilent). Table 2 shows the ratio of disease related expression (“R”) compared to normal tissues. Table 2 also shows the statistical analysis of the normalized signal (“RPval”). The signal of each probe was set as its median intensity. Signal intensities range from background level of 400 to saturating level of 66000. 2 channels hybridization was performed and Cy3 signals were compared to Cy5 signals, where fluor reversed chip was preformed (normal vs. disease), probe signal was set to be its average signal. Signals were normalized by dividing them with the known miRNAs average signals such that the sum of known miRNAs signal is the same in each experiment or channel. Signal ratios between disease and normal tissues were calculated. Signal ratio greater than 1.5 indicates a significant upregulation with a P value of 0.007 and signal ratio grater than 2 has P value of 0.003. P values were estimated based on the occurrences of such or greater signal ratios over duplicated experiments. The differential expression analysis in Table 2 indicates that the expression of a number of the miRNAs are significantly altered in disease tissue. In particular, the MC19-1 miRNAs of Example 4 are differentially expressed in prostate and lung cancer. The relevance of the MC19-1 miRNAs to cancer is supported by the identification of a loss of heterozygosity within the MC19-1 region in prostate cancer derived cells (Dumur et al. 2003). TABLE 3 SEQUENCED MICRORNAS HID MID Tissue 46 7060 7 88 7143 11 109 7186 7 109 7187 7 197 7362 7 197 7363 7 197 7364 7 197 7365 7 197 7366 7 230 7433 11 230 7434 11 235 7443 7 235 7444 7 235 7445 7 235 7446 7 248 7473 11 248 7474 11 283 7544 7 286 7549 7 286 7550 7 286 7551 7 286 7552 7 286 7553 7 289 7558 7 289 7559 7 289 7560 7 289 7561 7 289 7562 7 289 7563 7 289 7564 7 303 7591 7 303 7592 7 303 7593 7 303 7594 7 374 7737 11 449 7886 12 604 8195 12 679 8345 7 679 8346 7 699 8386 7 699 8387 7 699 8388 7 778 8547 11 841 8673 20 908 8808 7 908 8809 7 917 8828 11 917 8829 11 978 8950 11 1084 9162 10 1084 9163 10 1084 9164 10 1159 9315 7 1167 9330 7 1167 9331 7 1167 9332 7 1167 9333 7 1192 9383 7 1296 9591 7 1408 9816 7 1459 9918 12 1459 9919 12 1459 9920 12 1459 9921 12 1534 10070 11 1564 10129 7 1564 10130 7 1564 10131 7 1564 10132 7 1564 10133 7 1598 10201 7 1598 10202 7 1601 10207 7 1601 10208 7 1601 10209 7 1601 10210 7 1601 10211 7 1601 10212 7 1601 10213 7 1601 10214 7 1628 10268 7 1633 10278 9 1652 10315 7 1652 10316 7 1652 10317 7 1652 10318 7 1794 10601 7 1794 10603 7 1794 10604 7 1794 10605 7 1890 10797 6 1890 10798 6 1890 10799 6 1929 10876 7 1929 10878 7 1940 10899 7 1940 10900 7 1958 10936 11 1961 10941 11 1961 10943 11 1961 10944 11 2058 11137 7 2058 11138 7 2058 11139 7 2058 11140 7 2058 11141 7 2147 11320 7 2147 11321 7 2154 11336 7 2164 11357 7 2164 11358 7 2164 11359 7 2171 11374 11 2172 11375 7 2172 11376 7 2172 11377 7 2172 11378 7 2178 11389 7 2178 11390 7 2178 11391 7 2178 11392 12 2178 11393 12 2180 11397 7 2180 11398 7 2180 11399 7 2182 11403 11 2186 11412 11 2186 11413 11 2213 11467 7 2213 11468 7 2213 11469 7 2362 11766 12 2362 11767 12 2362 11768 12 2363 11769 12 2363 11770 12 2363 11771 12 2364 11772 12 2364 11773 12 2364 11774 12 2414 11873 7 2414 11874 7 2414 11875 7 2414 11876 7 2415 11877 7 2415 11878 7 2415 11879 7 2415 11880 7 2415 11881 7 2415 11882 7 2428 11907 7 2428 11908 7 2483 12019 11 2493 12039 7 2493 12040 7 2493 12041 7 2585 12224 7 2585 12226 7 2585 12227 7 2585 12228 7 2620 12297 21 2682 12421 7 2693 12443 7 2693 12444 7 2693 12445 7 2706 12470 7 2706 12471 7 2706 12472 7 2748 12555 21 2802 12663 7 2802 12664 7 2805 12670 11 2805 12671 11 2811 12683 7 2811 12684 7 2821 12703 11 2821 12704 11 2821 12705 11 2821 12706 11 2828 12719 7 2828 12720 7 2828 12721 7 2866 12798 7 2866 12799 7 2866 12800 7 3011 13090 11 3021 13109 7 3021 13110 7 3021 13111 7 3021 13112 7 3021 13113 7 3021 13114 7 3021 13115 7 3026 13126 11 3026 13127 11 3026 13128 11 3055 13186 11 3055 13187 11 3055 13188 11 3055 13189 11 3069 13218 7 3069 13219 12 3069 13220 12 3104 13291 7 3113 13308 11 3113 13310 11 3113 13311 19 3121 13327 24 3121 13328 24 3353 13791 11 3358 13801 7 3358 13802 7 3360 13806 5 3360 13807 7 3360 13808 7 3360 13809 7 3474 14036 7 3506 14099 7 3519 14125 7 3519 14126 7 3519 14127 7 3564 14216 11 3611 14309 7 3611 14310 7 3611 14311 7 3611 14312 7 3611 14313 7 3613 14318 11 3619 14330 7 3737 14566 13 3737 14567 13 3757 14606 12 3765 14621 11 3765 14622 11 3765 14623 11 3765 14624 11 3777 14647 7 3777 14648 7 3777 14649 7 3792 14679 7 3799 14693 12 3799 14694 12 3872 14840 7 3872 14841 7 3872 14842 7 3873 14844 7 3873 14845 7 3873 14846 7 3878 14855 7 3923 14944 7 3929 14956 11 3964 15025 7 3964 15026 7 3964 15027 7 3970 15040 7 3970 15041 7 3985 15070 7 3985 15071 7 3985 15072 7 3986 15073 7 3986 15074 7 3986 15075 7 3987 15076 7 3987 15077 7 3987 15078 7 3987 15079 7 3998 15102 7 4022 15150 7 4052 15209 7 4052 15210 7 4053 15211 7 4054 15212 7 4072 15247 7 4072 15248 7 4132 15367 7 4168 15439 7 4168 15440 7 4168 15441 7 4168 15442 7 4168 15443 7 4169 15444 7 4169 15445 7 4169 15446 7 4169 15447 7 4169 15448 7 4203 15516 12 4253 15617 11 4253 15618 11 4253 15619 11 4373 15860 11 4373 15861 7 4373 15862 11 4373 15863 11 4410 15936 27 4451 16017 26 4451 16018 23 4487 16091 7 4487 16092 11 4488 16095 11 4488 16096 11 4489 16098 14 4490 16100 14 4498 16115 7 4662 16443 11 4662 16444 11 4701 16523 11 4721 16562 12 4721 16563 12 4778 16678 19 4796 16715 11 4797 16718 11 4799 16722 11 4799 16723 11 4812 16748 7 4847 16818 7 4927 16978 7 4931 16986 7 4954 17033 7 4982 17088 11 4982 17089 7 4987 17098 11 4987 17100 11 4987 17101 19 4993 17113 7 4993 17114 7 5017 17163 11 5017 17164 11 5017 17165 11 5022 17175 7 5049 17229 11 5049 17230 11 5111 17354 7 5164 17459 11 5248 17627 11 5248 17629 7 5313 17758 7 5313 17760 7 5317 17768 12 5354 17842 7 5364 17861 20 5364 17862 20 5364 17863 7 5364 17864 7 5429 17995 11 5448 18032 11 5469 18073 7 5469 18074 7 5469 18075 7 5469 18076 7 5541 18219 11 5541 18220 11 5572 18281 7 5572 18282 7 5627 18392 7 5628 18393 7 5640 18417 7 5640 18418 7 5640 18419 7 5693 18526 7 5693 18527 7 5701 18542 19 5701 18544 19 5701 18545 19 5701 18546 19 5701 18547 20 5747 18639 7 5770 18685 7 5770 18686 7 5770 18687 7 5770 18688 7 5806 18760 12 5806 18761 12 5806 18762 12 5808 18765 7 5888 18925 12 5888 18926 12 5888 18927 12 5891 18933 19 5891 18934 19 5891 18935 19 5906 18965 11 5910 18972 7 5947 19045 11 5947 19047 19 5954 19061 7 5954 19062 7 5954 19063 7 5954 19064 7 5954 19065 7 5987 19132 11 6007 19171 7 6084 19324 10 6230 19618 11 6380 19918 9 6380 19919 9 6396 19950 7 6396 19951 7 6396 19952 7 6429 20017 7 6438 20034 11 6438 20036 11 6443 20045 7 6443 20046 7 6443 20047 7 6443 20048 7 6443 20049 7 6444 20050 11 6444 20052 11 6444 20053 11 6444 20054 11 6529 20223 7 6529 20224 7 6529 20225 7 6529 20226 7 6569 20305 7 6569 20306 7 6569 20307 7 6662 20494 7 6662 20495 7 6662 20496 7 6665 20501 7 6665 20502 7 6665 20503 7 6665 20504 7 6665 20505 7 6665 20506 7 6673 20521 11 6673 20522 11 6678 20531 11 6678 20532 11 6678 20533 11 6678 20534 11 6678 20535 11 6692 20562 7 6692 20563 7 6716 20611 22 6716 20612 22 6716 20613 22 6765 20710 10 6765 20712 10 6765 20713 10 6766 20714 7 6766 20715 7 6766 20716 7 6883 20949 7 6883 20951 7 6883 20952 7 6883 20953 7 6914 21015 7 6968 21122 7 6968 21123 7 TABLE 6
RELATION OF MICRORNAS TO DISEASES BY HOST GENES
7030, 7029
167, 157
7046, 7045
7052, 7051
7166, 7165
172, 171, 118, 127, 154, 41, 67, 92, 53, 40,
111, 51, 102
7174, 7173
7219, 7218
7223, 7222
7225, 7224
110, 133, 31
7347, 7346
7351, 7350
31, 176, 133, 110, 51, 167
7396, 7395
7420, 7419
110, 133, 18
7438, 7437
57, 98
7454, 7453
112, 56, 92, 160, 18
7462, 7461
31, 162, 154, 8, 123
7468, 7467
31, 51, 154
7512, 7511
31, 122, 35, 118, 112, 109
7568, 7567
7572, 7571
7588, 7587
154, 123, 110
7610, 7609
82, 77, 8
7664, 7663
7698, 7697
7714, 7713
31, 112, 109, 93, 35
7716, 7715
7739, 7738
162, 29, 120
7769, 7768
7781, 7780
7809, 7808
7888, 7887
7920, 7919
157, 70, 31
7948, 7947
154, 51
7950, 7949
7952, 7951
118, 79, 51, 154, 151
7998, 7997
8000, 7999
51, 31, 24, 90, 83
8108, 8107
8164, 8163
134, 132, 64
8219, 8218
166, 157
8229, 8228
144, 8, 24, 162
8239, 8238
167, 110, 31, 92
8249, 8248
118, 31, 167, 154, 141, 133
8253, 8252
8255, 8254
8283, 8282
8295, 8294
51, 31, 167, 133, 110
8325, 8324
8348, 8347
166, 157, 27
8350, 8349
8352, 8351
8354, 8353
8366, 8365
8410, 8409
118, 110, 98, 31, 180, 154, 79, 51
8418, 8417
60, 174, 102, 61
8444, 8443
8452, 8451
133, 110, 42, 31
8478, 8477
8551, 8550
8591, 8590
51, 35, 155, 112, 109, 90, 133, 122, 118
8597, 8596
8617, 8616
157, 110, 31
8637, 8636
8651, 8650
8667, 8666
82, 29, 47, 123
8669, 8668
64, 105, 85
8713, 8712
79, 31, 30, 154
8785, 8784
51, 31, 154
8845, 8844
8865, 8864
8885, 8884
8958, 8957
112, 93
9052, 9051
92, 56, 120, 18, 103, 160, 141
9056, 9055
9068, 9067
9100, 9099
9132, 9131
9168, 9167
112, 109, 93
9202, 9201
26, 42, 30, 27, 83, 51, 48, 166, 110
9226, 9225
162, 77, 8
9246, 9245
9260, 9259
8, 77, 82, 162
9272, 9271
9274, 9273
9302, 9301
9361, 9360
9481, 9480
31, 154, 118, 79, 51
9505, 9504
31, 157, 110
9517, 9516
9527, 9526
154, 31
9581, 9580
60, 133, 31, 51, 67, 110, 92, 105, 64, 132
9593, 9592
9595, 9594
9597, 9596
116, 8, 109, 157
9637, 9636
9689, 9688
9705, 9704
9723, 9722
9733, 9732
9753, 9752
9769, 9768
9779, 9778
9826, 9825
9854, 9853
31, 90, 79, 154
9870, 9869
134, 31
10029, 10028
10039, 10038
10043, 10042
31, 8, 92, 144, 123
10051, 10050
160, 136, 31
10084, 10083
10086, 10085
10096, 10095
10224, 10223
10298, 10297
48, 56, 49
10338, 10337
10340, 10339
51, 154, 109
10356, 10355
10444, 10443
10520, 10519
109, 90, 47, 134, 122, 112
10546, 10545
10556, 10555
10566, 10565
10619, 10618
110, 154, 118, 31
10641, 10640
10749, 10748
10771, 10770
10775, 10774
10799, 10798, 10797, 10796
10819, 10818
134, 95, 51, 154
10841, 10840
10849, 10848
110, 109, 133
10884, 10883
10920, 10919
122, 83, 31
10936, 10935
10968, 10967
11038, 11037
11040, 11039
11078, 11077
11096, 11095
112, 109, 92, 157
11275, 11274
11309, 11308
154, 51, 30
11317, 11316
109, 105, 64, 123
11325, 11324
11340, 11339
110, 31, 90, 109, 112, 154, 133, 51
11403, 11402
11461, 11460
11507, 11506
11573, 11572
11579, 11578
8, 167, 157, 92, 51, 31, 133, 110
11581, 11580
11605, 11604
64, 53, 31, 105, 103, 92, 132
11609, 11608
11613, 11612
11617, 11616
11723, 11722
11804, 11803
11844, 11843
11870, 11869
11886, 11885
11914, 11913
11954, 11953
11998, 11997
12012, 12011
31, 110, 133, 51
12016, 12015
118, 112, 110, 51, 35, 31, 109, 90, 59
12043, 12042
12051, 12050
24, 133
12089, 12088
31, 8, 154, 51
12131, 12130
12141, 12140
12153, 12152
12157, 12156
12171, 12170
12221, 12220
12236, 12235
12248, 12247
51, 31, 8, 105, 92, 64, 134, 110
12288, 12287
82, 77, 70, 10
12329, 12328
12359, 12358
12381, 12380
51, 31, 30, 112, 110, 109, 176, 133
12393, 12392
12411, 12410
12528, 12527
12597, 12596
166, 118
12621, 12620
12635, 12634
12677, 12676
30, 157, 106, 83, 51, 31
12727, 12726
98, 63, 8, 160, 111, 109
12747, 12746
12771, 12770
12785, 12784
12830, 12829
12834, 12833
109, 51
12842, 12841
12852, 12851
12902, 12901
118, 60
12904, 12903
12932, 12931
167, 133, 110, 8
12944, 12943
12954, 12953
13000, 12999
13014, 13013
13028, 13027
13064, 13063
13074, 13073
13119, 13118
51, 31, 110
13154, 13153
13180, 13179
13191, 13190
13293, 13292
13430, 13429
13442, 13441
13514, 13513
138, 51
13530, 13529
13540, 13539
13586, 13585
13686, 13685
181, 154, 30
13702, 13701
154, 92, 110, 51, 8, 31
13710, 13709
13762, 13761
13811, 13810
13907, 13906
82, 77, 29
13933, 13932
167, 105, 162, 29, 24, 144, 36, 64, 23, 133
13943, 13942
14066, 14065
64, 51, 42, 132, 108, 98, 31, 174, 134
14096, 14095
14173, 14172
14211, 14210
14272, 14271
14304, 14303
14318, 14317, 14316
14328, 14327
14460, 14459
14478, 14477
14601, 14600
14605, 14604
14651, 14650
14683, 14682
14702, 14701
31, 133, 110
14808, 14807
14869, 14868
14879, 14878
14903, 14902
14946, 14945
14954, 14953
64, 105
14956, 14955
14968, 14967
15008, 15007
70, 8, 109
15099, 15098
51, 31, 150, 110, 64, 8, 132
15106, 15105
15118, 15117
109, 160
15134, 15133
15146, 15145
15156, 15155
110, 51, 31
15222, 15221
15242, 15241
15274, 15273
15276, 15275
15376, 15375
15394, 15393
15408, 15407
15424, 15423
15428, 15427
15452, 15451
15468, 15467
15532, 15531
15544, 15543
64, 31, 51, 132, 110, 105, 134
15568, 15567
15574, 15573
15653, 15652
31, 118, 110, 51, 167
15663, 15662
88, 51, 118, 90
15685, 15684
133, 31, 110, 51
15691, 15690
31, 116, 173, 167, 8
15713, 15712
15743, 15742
75, 51, 8
15759, 15758
15801, 15800
15817, 15816
15833, 15832
15885, 15884
110, 51, 31, 133
15895, 15894
15899, 15898
15919, 15918
15921, 15920
15929, 15928
133, 51, 31, 167
15960, 15959
15962, 15961
16008, 16007
16024, 16023
16054, 16053
16056, 16055
98, 64, 8, 105
16060, 16059
16068, 16067
16070, 16069
16076, 16075
16137, 16136
16177, 16176
16213, 16212
16293, 16292
16297, 16296
16311, 16310
16335, 16334
16355, 16354
10, 154, 8, 162
16357, 16356
16375, 16374
16437, 16436
16439, 16438
16464, 16463
16468, 16467
16480, 16479
16510, 16509
16533, 16532
16543, 16542
16549, 16548
16567, 16566
157, 150
16643, 16642
16706, 16705
16729, 16728
16840, 16839
16852, 16851
16868, 16867
16896, 16895
93, 157, 111
16918, 16917
70, 92, 160
16920, 16919
8, 62, 10, 162, 29
16924, 16923
16942, 16941
16962, 16961
16982, 16981
16996, 16995
17006, 17005
17043, 17042
17130, 17129
110, 133, 154, 26, 176, 167, 51, 31, 30
17183, 17182
17205, 17204
17211, 17210
17272, 17271
17290, 17289
17384, 17383
83, 31
17400, 17399
17410, 17409
17418, 17417
17464, 17463
17480, 17479
17510, 17509
17594, 17593
17659, 17658
17751, 17750
17796, 17795
17798, 17797
17834, 17833
17860, 17859
17948, 17947
17954, 17953
18146, 18145
18174, 18173
172, 127
18250, 18249
18264, 18263
18344, 18343
18397, 18396
18409, 18408
90, 51, 79, 31, 112, 110
18413, 18412
157, 154, 150, 133, 31, 167
18433, 18432
18479, 18478
18511, 18510
18535, 18534
18567, 18566
18587, 18586
132, 92, 64, 134
18595, 18594
18621, 18620
18635, 18634
18675, 18674
18754, 18753
18789, 18788
18803, 18802
18813, 18812
18815, 18814
18887, 18886
133, 110, 31, 8
18931, 18930
18955, 18954
18978, 18977
18998, 18997
30, 27, 166, 83, 31
19036, 19035
19038, 19037
19091, 19090
19170, 19169
19207, 19206
19245, 19244
19271, 19270
19297, 19296
19321, 19320
19393, 19392
19411, 19410
19459, 19458
19461, 19460
19475, 19474
19485, 19484
19583, 19582
19597, 19596
19624, 19623
19668, 19667
97, 64, 53, 132, 105
109, 31, 4, 166, 157, 118
19728, 19727
19736, 19735
19812, 19811
133, 110, 90, 154, 31
19816, 19815
19834, 19833
19842, 19841
19846, 19845
133, 110, 51
19929, 19928
152, 51
19956, 19955
19976, 19975
19996, 19995
20000, 19999
20002, 20001
20060, 20059
20172, 20171
20176, 20175
20208, 20207
20252, 20251
20311, 20310
20319, 20318
20323, 20322
20329, 20328
20333, 20332
20345, 20344
20369, 20368
20373, 20372
FLJ22795
51, 110
20391, 20390
20393, 20392
20397, 20396
20516, 20515
20518, 20517
20528, 20527
20571, 20570
20665, 20664
20693, 20692
20701, 20700
20736, 20735
20742, 20741
20762, 20761
20806, 20805
20822, 20821
20826, 20825
20854, 20853
20872, 20871
20876, 20875
31, 157
20878, 20877
20918, 20917
21023, 21022
21107, 21106
51, 109
TISSUE AND DISEASE CODES FOR TABLE 2 AND 3
Tissue or Disease name
Uterus carcinoma cell line (HeLa)
Lung carcinoma cell line (H1299)
Lung carcinoma cell line (H1299) with P53
Overy and Small Intestine (mixture)
Embryonic Stem carcinoma cells
Brain with Alzheimer
Uterus carcinoma cell line (cMagi) with HIV
T cell line (MT2)
T cell line (MT2) with HIV
Placenta and Brain Substantia Nigra (mixture)
T cell line (MT2) with HIV and Brain Substantia Nigra (mixture)
T cell line (MT2) with HIV and Lung adenocarcinoma (mixture)
DISEASE CODES FOR TABLES 5 AND 6
Atrophic gastriris
Hypertrophic Cardiomopathy
RELATION OF TARGET GENES TO DISEASE
27, 118
AECA1
31, 51, 92, 167, 110, 133, 152
31, 44, 45
30, 110, 133, 167
31, 109, 110
31, 51, 109
42, 79, 154
8, 31, 65, 110, 127, 133
64, 105, 134
31, 107, 160
30, 154, 181
8, 31, 51, 167
100, 129, 162
110, 157, 167
21, 135
47, 90, 109, 112, 122, 134
110, 140, 150, 154, 167
31, 127
3, 52, 64, 132, 154, 79, 85, 108
8, 58, 186
31, 51, 110
8, 23, 62, 134, 162
8, 52, 53, 98, 134
8, 18, 58, 132, 134, 64, 97, 98
53, 64, 67, 134, 97, 98, 132
53, 58, 98, 160
8, 9, 64, 146, 105, 132, 133
8, 64, 65, 98, 105, 132
3, 15, 53, 127, 98, 99, 105, 64, 65, 95
57, 95, 108
31, 79, 110, 154
1, 64, 105, 174
64, 66, 90, 105
10, 31, 64, 133, 154, 162, 79, 110, 132
31, 83, 110
31, 51, 110, 154
4, 8, 31, 133, 167, 105, 110, 132, 51, 64, 92
133, 157
31, 83, 90
64, 98, 132, 154
51, 154
18, 31, 92, 140, 154, 180, 109, 110, 112
18, 92, 127, 168
30, 118, 133, 154
31, 42, 51, 109, 118, 154
31, 42, 133
31, 51, 90
31, 83, 110, 154
110, 154, 167
8, 61, 103, 107, 121
8, 51, 75
31, 51, 83, 167, 151, 152, 154, 106, 110, 133
8, 9, 64, 132
10, 42, 51, 109
12, 64, 92, 98, 132, 134
64, 95, 98, 127, 132
8, 9, 53, 134, 141, 105, 127, 132, 64, 95, 97
4, 8, 31, 105, 132, 64, 92, 95
8, 64, 95, 97, 132
8, 64, 132
8, 53, 64, 134, 97, 105, 132
8, 29, 31, 132, 162, 64, 123, 127
8, 9, 31, 123, 162
131, 182
8, 31, 51, 92, 110, 154
30, 31, 42, 155, 133, 51, 154
31, 51, 89, 154, 159, 90, 110, 118
31, 51, 157
31, 109
20, 106, 154
47, 88, 90
31, 110, 118
31, 93, 112
8, 64, 98, 105
60, 158
31, 51, 112
AUTS4
24, 57, 98
36, 57, 110, 150
51, 90, 109, 110, 167
4, 8, 9, 123, 133, 92, 110, 118, 31, 51, 77
8, 31, 51, 70
8, 109, 110, 118
31, 42, 109
51, 110, 133
8, 31, 51, 166, 110, 133, 154
8, 31, 51, 123, 167, 110, 133
2, 31, 118
31, 42, 51, 157, 112, 122, 154, 79, 109, 110
93, 109, 112
4, 8, 31, 167, 112, 123, 133, 51, 92, 110
8, 31, 51, 167, 123, 133, 154, 92, 110, 122
48, 49, 83, 109, 112
4, 31, 112
18, 64, 92, 132, 154, 160
31, 64, 92, 136, 105, 110, 132
31, 118, 154
42, 83, 123
110, 112, 122, 123
51, 109, 122, 133
31, 51, 110, 133, 140
51, 106, 109
8, 35, 112
4, 92, 109, 112, 122, 123
51, 110, 118
31, 51, 138
31, 51, 110, 133, 140, 154
92, 118, 166
51, 109, 110, 112, 133
51, 109, 112
8, 31, 162
8, 77, 123
8, 111
8, 31, 51, 110, 134, 64, 92, 105
18, 119, 123
64, 105, 111, 127
8, 92, 119, 127
18, 92, 119, 123
8, 63, 119, 123, 127
109, 133, 141
31, 42, 51, 118, 133, 157
82, 167
8, 10, 51, 82, 144
8, 51, 162
110, 136, 167
31, 136, 160
35, 38, 51, 160, 111, 112, 154
56, 103, 156, 180
4, 31, 51, 92, 123
93, 112, 133
8, 31, 42, 154, 110, 123, 133, 51, 92, 109
51, 79, 133
31, 51, 154, 157
8, 31, 51, 157, 167, 92, 110, 133
4, 8, 31, 122, 133, 51, 90, 110
31, 64, 132, 136
8, 63, 98, 109, 111, 160
4, 8, 31, 110, 132, 133, 51, 64, 92
31, 47, 51, 154, 155, 83, 92, 110
8, 64, 132, 167
44, 64, 132, 134, 141, 162
51, 64, 110, 132, 162, 167
5, 92, 125, 159
18, 20, 56, 165, 180, 183, 92, 93, 159
5, 18, 20, 93, 109
8, 31, 64, 167, 123, 132, 133, 92, 105, 110
4, 31, 51, 92, 94, 123
4, 8, 31, 123, 133, 92, 94, 110
31, 42, 92, 94, 123, 133
18, 20, 92, 123, 180
8, 31, 51, 110, 133
31, 51, 110, 180, 133, 112, 122, 167
31, 35, 109, 112, 118, 122
31, 110, 133, 167
31, 42, 109, 133, 167
88, 91, 92, 123, 160
4, 18, 61, 135, 136, 160, 92, 122, 123
18, 20, 92, 93, 123
18, 20, 88, 112, 123, 92, 93, 111
4, 61, 92, 123
94, 109, 112, 122, 160
31, 59, 92, 118, 93, 109, 112
18, 46, 92, 123
109, 123, 160
31, 51, 92, 110
20, 123
64, 105, 109
31, 35, 90, 133, 154, 167, 109, 110, 112
31, 64, 92, 167, 114, 171, 110, 132
4, 64, 92, 105, 132
93, 111, 157
4, 31, 92, 111
31, 51, 92, 133, 157, 109, 110, 123
31, 51, 64, 92, 105
4, 8, 31, 114, 51, 92, 110
18, 31, 64, 160, 178, 92, 105, 111
110, 133, 167
31, 51, 64, 123, 105, 92, 110
31, 92, 109, 157
31, 51, 64, 92, 105, 123
38, 88, 92, 93, 109, 157
31, 51, 133, 167
8, 31, 51, 167, 92, 110, 133
31, 51, 83, 112, 133
79, 112, 166
31, 51, 110, 133, 167, 176
31, 112
31, 42, 51, 110, 133
8, 31, 51, 110, 118, 133
31, 51, 79, 133, 167, 180, 90, 92, 110
3, 30, 31, 110, 141, 51, 90, 109
8, 31, 51, 133, 140, 167, 109, 110, 118
CDKN2A_ARF
31, 51, 110, 133, 180
8, 31, 94, 122, 133, 109, 112, 118
31, 109, 110, 167
CDPD1
109, 123, 160, 174
51, 106, 151
31, 51, 79, 154, 90, 110, 118
31, 51, 110, 133
31, 51, 109, 133
135, 157, 160
31, 90, 109, 110
31, 51, 92
53, 64, 105, 132
93, 109, 112, 118, 122, 123
18, 32, 58, 102, 141
30, 31, 70, 110, 150
31, 110, 133
8, 10, 124
31, 51, 110, 154, 167
36, 110, 167
31, 51, 166
8, 144, 162
8, 18, 62, 162, 169
8, 18, 51, 154
8, 18, 144
8, 24, 82, 144
8, 24, 144, 162
82, 162
35, 90, 109, 112
8, 109, 127
8, 10, 31, 127, 154
CMD1H
CMD1K
8, 70, 123
31, 144, 154, 162
8, 10, 122, 162
27, 91, 154
31, 35, 90, 112, 157, 109, 133
83, 154, 157
23, 29, 31, 62, 144, 162
8, 64, 105, 110, 132, 144
127, 172
29, 162
4, 47, 92, 123, 160, 110, 111, 122
18, 75, 92, 109, 111
42, 79, 109
3, 94, 102, 111, 154
8, 110, 123
8, 57, 160
8, 37, 75, 123, 129
8, 47, 64, 132
4, 31, 51, 166, 167, 92, 110, 133
4, 31, 64, 133, 167, 92, 110, 132
31, 70, 85
31, 109, 118, 154
129, 154
8, 9, 10, 123, 51, 53, 110
51, 83, 110, 157, 112, 118, 122
31, 47, 64, 109, 65, 103, 105
1, 18, 38, 174, 123, 124, 160, 105, 111, 122, 64, 92, 93
51, 152
31, 51, 90, 110, 133
30, 51, 118, 133, 154
8, 31, 51, 110, 123, 133
8, 31, 51, 92
8, 41, 56, 127, 172, 180
22, 31, 51, 76, 83, 118
8, 70, 110
56, 77, 92, 160
30, 154
56, 74, 104, 166, 155, 160, 118, 135, 154
31, 51, 77, 133, 92, 110, 123
4, 31, 52, 154, 160, 106, 109, 112, 61, 90, 92
74, 118
74, 110, 126, 133, 160
5, 58, 88, 123
31, 52, 91, 160, 170, 92, 154, 157
31, 79, 90, 154
27, 31, 51, 110, 154, 157, 79, 83, 88
51, 88, 141, 162
31, 51, 83, 110, 154, 166
1, 64, 105
42, 51, 154
51, 83, 110
45, 88, 110
10, 11, 27, 162, 88, 110, 144, 30, 31, 62
90, 92, 109, 154
31, 133
118, 166
4, 42, 51, 114, 123, 109, 110, 112
30, 31, 51, 133, 176, 109, 110, 112
30, 176
23, 29, 162
8, 47, 162
70, 109, 154
23, 24, 29, 167, 133, 144, 162, 36, 64, 105
51, 112
4, 110, 129, 167
29, 62, 162
51, 83, 110, 133, 154, 167
58, 111
30, 31, 51, 176, 152, 154, 157, 88, 90, 110
30, 51, 88, 133, 157, 167, 90, 109, 110
4, 51, 64, 154, 161, 92, 118, 132
30, 31, 51, 83, 106, 157
8, 29, 98, 144, 162
8, 110, 162, 167
23, 29, 73, 144, 162
12, 23, 29, 144, 162
23, 24, 29, 144, 162
70, 118
31, 129
51, 68, 110, 122, 134, 154
30, 31, 51, 154
31, 51, 79, 109, 154, 180
30, 31, 83, 133, 140
30, 31, 51, 129
31, 42, 51, 132, 134, 174, 64, 98, 108
31, 51, 110, 118, 157
31, 51, 110, 133, 167
EGI14
8, 31, 110, 133
8, 31, 110, 118
133, 167
31, 110, 154
31, 51, 110, 118, 133, 154
31, 110, 111
8, 157
110, 118, 133, 160
93, 109, 112, 118
ENUR2
30, 31, 133, 157
31, 51, 110, 157, 118, 133, 154
118, 133, 157, 167
30, 46, 76, 90, 110
4, 31, 92, 110, 133, 167
18, 31, 78, 180
26, 30, 31, 154, 167, 176, 51, 110, 133
31, 51, 110, 154, 166, 118, 133, 140
42, 51, 109, 133
27, 83, 110, 118
30, 51, 140, 154
4, 8, 92, 123
31, 42, 51, 70, 90, 154
109, 112, 154
109, 127, 172
88, 172
48, 49, 56
8, 31, 51, 133, 64, 105, 132
31, 172
4, 8, 31, 133, 51, 64, 132
53, 103, 127, 168, 172
64, 127, 132, 172
53, 64, 97, 105, 132, 134
30, 155
51, 64, 105, 133
31, 109, 113
31, 51, 110, 152, 154, 180
31, 51, 112, 157
18, 20, 88, 123, 160, 92, 109, 111
18, 111, 161, 171
31, 109, 110, 112, 118
9, 21, 172
52, 53, 98, 127, 146, 172
31, 53, 64, 109, 154
31, 110, 167
31, 154, 157
8, 31, 51, 133
30, 31, 79, 154
30, 42, 51, 109, 122, 176
31, 51, 150
31, 42, 110, 133
FLJ11383
16, 109, 111, 112, 157, 160
31, 51, 90, 133, 154, 109, 110, 112
8, 31, 92, 110, 123, 133
31, 42, 51, 83, 110, 167
31, 42, 83
30, 92, 102, 150
8, 37, 144
114, 162
92, 109, 112, 157
30, 31, 42, 109, 111
8, 31, 51, 64, 86, 132
29, 47, 82, 123
24, 29, 49
8, 64, 82, 105, 144, 162
64, 66, 82, 174, 105, 132, 162
109, 110, 118
8, 12, 57, 134, 150
8, 10, 29, 62, 162
8, 31, 51, 64, 105
51, 64, 132
31, 60, 92
64, 105, 123, 132
64, 85, 98, 105, 132
51, 86, 109
4, 8, 123
12, 31, 47, 107, 134, 154, 64, 90, 105
12, 64, 132, 134, 150, 154
51, 157
30, 31, 60, 155, 79, 90, 118
27, 112
8, 90, 123
110, 150, 186
57, 150, 154
8, 29, 53, 127, 132, 134, 64, 65, 98
86, 160
5, 20, 118, 155
91, 98, 160
86, 110, 154
8, 31, 109
29, 77, 82
8, 77, 82
10, 70, 77, 82
8, 10, 29, 62, 82, 162
8, 77, 162
10, 162
51, 71, 83, 110, 154, 167
9, 30, 31, 154, 58, 110, 133
8, 31, 51, 110, 167, 64, 86, 105
30, 51, 57, 154
18, 27, 31, 51, 110, 123
30, 31, 51, 110
8, 31, 51, 110
64, 132, 134
75, 92, 160
7, 64, 105
28, 114, 163
92, 109
28, 47, 64, 88, 105, 144
31, 51, 83, 133, 109, 110, 112
51, 109, 154
31, 84, 111
64, 86, 132
51, 64, 83, 118, 157, 162, 88, 92, 105
42, 51, 64, 156, 118, 123, 155, 83, 92, 105
64, 105, 123, 160
38, 48, 64, 123, 124, 160, 93, 105, 109
64, 105, 132
64, 88, 105, 160, 174, 111, 123, 156
51, 56, 64, 123, 132, 92, 105, 111
38, 47, 109, 125
64, 105, 109, 123
59, 64, 77, 105, 123
92, 109, 112, 118, 157, 166
26, 83, 112
31, 90, 180
8, 31, 51, 132, 64, 95, 110
31, 51, 109, 112, 122
8, 123, 127, 144, 157
64, 90, 132
18, 70, 72, 161, 162
83, 92, 110, 167, 111, 133, 160
24, 31, 110
102, 109, 133
109, 171
27, 157, 166
31, 64, 92, 105, 141
107, 109, 110, 118, 123
31, 110, 118, 157
4, 18, 46, 107, 127
8, 18, 183
HSAJ2425
51, 79, 154
31, 51, 160
8, 31, 100
31, 111
8, 64, 105
8, 29, 62, 64, 132, 162
8, 12, 23, 120, 162, 24, 29, 62
29, 120, 162
8, 29, 162
9, 58, 64, 132, 134
61, 129, 139
31, 51, 110, 122, 154
56, 92, 160, 180
56, 92, 93, 160, 174, 180, 111, 112, 123
31, 42, 79, 154, 83, 118, 141
4, 79, 88, 157, 92, 109, 118
4, 31, 51, 123, 133, 110, 115, 118, 77, 91, 92
31, 42, 51, 178, 110, 133, 167
47, 92, 111, 114, 125, 178
31, 51, 60, 133, 105, 110, 132, 64, 67, 92
31, 110, 118, 154
4, 8, 31, 110, 132, 51, 64, 105
31, 51, 90, 110
47, 64, 105
31, 51, 64, 105, 132
31, 51, 64, 134, 105, 110, 132
31, 51, 64, 154, 107, 110, 132
31, 42, 64, 154, 79, 105, 107
31, 90, 110, 133, 154
4, 8, 31, 133, 178, 110, 112, 123, 92, 105, 106, 35, 51, 64
20, 56, 92, 118, 123, 154
64, 92, 105, 123, 154
4, 18, 31, 105, 123, 159, 51, 64, 92
93, 175
18, 175
31, 92, 110, 167
18, 56, 92, 112, 160
4, 8, 31, 133, 105, 110, 123, 75, 90, 92, 51, 61, 64
64, 105, 135
4, 8, 31, 132, 167, 110, 118, 123, 64, 92, 105
104, 110, 118, 133
31, 51, 64, 133, 155, 167, 92, 105, 123
92, 109, 110, 118, 162
56, 77, 123
4, 8, 31, 109, 123, 133
4, 8, 31, 133, 105, 110, 123, 51, 64, 92
18, 64, 105, 112, 123, 157
31, 64, 92, 133, 105, 110, 123
4, 31, 42, 127, 150, 112, 122, 123, 56, 77, 92
4, 8, 31, 92, 110, 133
4, 31, 51, 110, 123, 133, 64, 92, 105
4, 92, 154, 155, 178
31, 65, 152, 154
31, 83, 118
8, 64, 85, 132, 134, 92, 98, 105
8, 31, 64, 132, 134, 85, 105, 129
31, 64, 85, 132, 134
IRTA1
31, 109, 118
31, 51, 110, 127, 169, 171
53, 64, 127, 154, 171
31, 51, 79, 118, 154
31, 92, 123
35, 51, 90, 133, 118, 155, 109, 112, 122
27, 31, 51, 175, 154, 160, 166, 90, 110, 142
4, 51, 92, 123
4, 8, 31, 92, 123
4, 31, 51, 167, 110, 123, 133, 64, 92, 105
92, 123
40, 41, 51, 172, 127, 154, 171, 102, 111, 118, 53, 67, 92
64, 105, 109, 112, 122
31, 42, 75, 155, 83, 110, 133
42, 83, 122
31, 122, 154, 157
31, 51, 109, 154, 122
20, 109, 112, 157
31, 92, 93, 109, 112
31, 51, 118, 133
30, 31, 42, 133, 154, 51, 83, 110
31, 64, 132
64, 70, 132
92, 155
31, 118
31, 51, 92, 167, 109, 110, 183
31, 51, 92, 110, 133, 167
107, 136, 157
31, 51, 152
31, 53, 154
79, 98, 141
31, 107, 154
59, 92, 102, 118
31, 47, 110, 133
31, 45, 47, 110
49, 118
8, 51, 67, 110
51, 83, 133, 166
31, 51, 83
31, 51, 110, 118, 133
64, 95, 97, 132
51, 64, 75, 167, 109, 110, 157, 83, 92, 105
17, 51, 56, 69, 103, 180
31, 112, 154
51, 64, 95, 110, 132
51, 112, 118
31, 64, 85, 133, 134, 92, 105, 132
12, 31, 33, 134, 109, 150, 105, 64, 92, 110
30, 31, 51, 110, 154
31, 88, 92, 133, 106, 110, 112
31, 109, 122
53, 64, 97, 105, 132
64, 97, 132, 134
21, 31, 42, 129, 133, 154, 51, 83, 110
31, 42, 51, 83, 133, 154
8, 64, 105, 132
8, 31, 53, 118, 154
64, 105, 136
31, 51, 64, 127, 110, 132, 105, 92, 123
47, 88, 160
18, 109, 165
4, 8, 31, 92
35, 51, 109, 112
31, 83, 133, 154
110, 166
112, 154
31, 109, 112
56, 103, 109, 112, 180
31, 51, 56, 83, 152, 180
31, 110, 133, 140, 151
56, 90, 180
24, 123
30, 31, 110, 118
83, 110, 118
110, 112, 166
8, 13, 23, 144, 162, 24, 29, 62
8, 10, 23, 162, 24, 29, 144
8, 82, 118, 144, 162
46, 137, 154
79, 154
31, 51, 64, 132
8, 31, 51, 92, 133, 167
8, 61, 70, 144
4, 58, 88, 92, 114, 163
4, 8, 24, 61, 123
27, 118, 154, 166
12, 33, 134
31, 51, 83, 110, 152
91, 110, 123
8, 51, 71, 106, 110
31, 36, 110, 167
51, 88, 90, 118
64, 77, 92, 123, 160, 167, 105, 110, 112
51, 118, 157
1, 38, 56, 166, 178, 180, 64, 105, 155
110, 118, 157, 166
61, 162, 184
31, 51, 103, 166, 110, 133, 151
8, 110, 133, 167
31, 51, 67, 166
14, 31, 42, 160, 166, 83, 118, 135
4, 8, 10, 144, 167, 123, 132, 133, 64, 110, 118, 31, 51, 61
79, 110, 154
31, 51, 56, 123, 167, 180
118, 160
31, 51, 110, 112, 133
31, 42, 102
8, 110, 123, 167
31, 51, 79, 151, 154, 106, 112, 138
31, 51, 79, 152, 109, 167, 83, 133
51, 138, 151
31, 42, 51, 79, 83, 110
8, 97, 154
30, 31, 154
31, 135, 154
8, 31, 154
109, 110, 133
8, 51, 100, 129
8, 31, 51, 132, 53, 64, 110
8, 129, 144
70, 117
56, 180
26, 51, 106, 110, 133, 141
58, 110, 133
26, 31, 51, 56, 110
102, 110, 165
88, 104, 123, 143, 159
MYAS1
35, 109, 112
30, 31, 42, 122, 133, 51, 83, 110
51, 110, 154
8, 24, 31, 133, 167, 51, 92, 110
8, 56, 64, 132
92, 109, 111
31, 109, 154
31, 79, 109, 154
31, 154, 173
8, 10, 144
8, 10, 31, 154, 70, 61, 123
31, 51, 110, 118, 167
31, 92, 133
31, 109, 112, 122
31, 51, 92, 110, 133
123, 160, 180
8, 123, 154
8, 31, 92, 123, 144
31, 90, 110, 133
30, 51, 92
8, 10, 18, 98, 144
4, 8, 31, 114, 132, 133, 98, 105, 110, 64, 88, 92, 51, 58, 61
8, 31, 54, 64, 110, 132
42, 51, 109, 167
3, 31, 154, 157
18, 109, 112, 174
64, 98, 105, 132, 167
8, 31, 64, 92, 132
8, 30, 31, 133, 154, 182, 51, 109, 110
31, 142, 163
3, 31, 57
4, 8, 31, 167, 110, 132, 134, 57, 64, 92
29, 144, 162
8, 31, 123, 154, 162
8, 10, 118, 154, 162
8, 31, 116, 167, 173
8, 10, 154, 162
8, 109, 116, 157
8, 110, 144, 154, 162, 167
31, 47, 51, 154, 90, 93, 110
OADIP
88, 109, 118, 122
OB10P
OB10Q
56, 74, 92, 180
51, 83, 110, 133, 154, 157
8, 92, 144
31, 92, 110, 154, 118, 122, 133
4, 110, 123, 167
31, 141
31, 92, 110
110, 123, 154
61, 144
8, 10, 144, 154, 157
30, 37, 51, 64
31, 64, 92, 150, 167, 110, 132, 134
24, 64, 110, 132, 167
27, 106, 109, 166
51, 89, 90, 133, 154
24, 29, 46, 62, 162
31, 47, 56, 163, 174, 180, 135, 157, 160, 123, 127, 133, 109, 110, 118
31, 145
51, 70, 110, 118, 157
30, 31, 110
16, 86, 144
31, 128, 155
42, 110, 133, 138
31, 51, 64, 93, 132
31, 51, 106, 157, 110, 133, 142
51, 118, 141, 152, 154
4, 18, 41
31, 51, 64, 133, 152, 123, 132, 134, 92, 105, 110
8, 31, 51, 133, 152, 92, 110, 123
31, 51, 92, 110, 123, 133
8, 29, 51, 54, 152
29, 31, 51, 152
92, 154
51, 83, 110, 112, 133
64, 76, 105, 146, 132, 134
51, 79, 118, 151, 154
8, 98, 144
30, 31, 51, 109, 110, 154
4, 8, 31, 167, 132, 110, 123, 134, 64, 92, 105
41, 52, 53, 132, 105, 144, 95, 64, 127
41, 52, 53
3, 31, 110
30, 64, 97, 132, 154
51, 64, 132, 133, 167
31, 51, 79, 90, 110, 112
8, 70, 109
14, 51, 88, 92, 122, 123
18, 174
31, 57, 111, 150, 154, 173
8, 31, 51, 150, 64, 110, 132
8, 31, 51, 154, 167, 92, 110, 133
8, 31, 51, 154
64, 109, 132, 134
8, 31, 51, 118, 187, 91, 92, 109
4, 12, 31, 105, 111, 123, 51, 64, 92
31, 150, 154
56, 58, 92, 180, 109, 111, 160
8, 9, 39, 70, 61
64, 105, 118, 174
18, 31, 50, 51, 118
27, 30, 31, 83, 166
31, 51, 79, 167, 173, 110, 133, 154
30, 42, 51, 79
98, 127
31, 51, 133
3, 4, 31, 136, 98, 110, 132, 51, 64, 92
31, 167
31, 118, 133, 141, 154, 167
8, 31, 64, 134, 83, 98, 132
31, 35, 93, 109, 112
64, 92, 105, 123
31, 134
31, 110, 157
31, 51, 56, 110
64, 85, 105
31, 51, 110, 150
31, 51, 83, 167, 118, 92, 154
31, 113, 150
31, 51, 93, 112
118, 157, 176
27, 51, 110
30, 31, 110, 133, 157, 167
30, 31, 51, 110, 167, 133
31, 35, 79, 110, 112, 133
31, 79, 107, 166
RCCP3
31, 92, 93, 112
8, 31, 92, 110
24, 29, 83, 162
8, 64, 65, 105, 132
116, 173
31, 64, 132, 134
136, 154
31, 118, 133
31, 155
56, 58, 155, 180
31, 56, 154, 180
31, 118, 133, 154, 167, 180
8, 36, 160
34, 185
SCZD10
31, 42, 51, 122, 90, 110, 112
36, 60, 106
SE20-4
4, 31, 51, 132, 133, 105, 110, 123, 64, 85, 92
4, 64, 92, 132, 105, 109, 123
31, 64, 92, 95, 105, 132
47, 58, 90, 107, 110
8, 31, 110
10, 31, 67, 113
40, 47, 52, 109, 127, 154
8, 74, 111, 112, 141, 160
31, 51, 180
137, 159
104, 159, 178
16, 75, 88, 160, 101, 109, 112
31, 64, 92, 134, 154, 98, 105, 132
8, 31, 64, 132
27, 49, 110, 166
26, 56, 74, 83
31, 51, 90, 154
30, 118, 176
31, 51, 90, 109, 110, 112
56, 178, 180
144, 162
64, 117
10, 29, 82, 162
8, 10, 82, 162
60, 173
8, 31, 51, 133, 105, 110, 132, 64, 65, 92
64, 105, 110, 132, 134
8, 31, 92, 110, 133
31, 64, 85, 134, 105, 106, 132
8, 86, 114, 158
12, 23, 29, 62, 162
23, 29, 144, 162
8, 13, 23, 162, 120, 144, 153, 62, 70, 98, 24, 29, 53
65, 98, 109
18, 58, 76, 177, 92, 110, 133
27, 166
8, 23, 29, 62, 162
8, 31, 144
8, 10, 31, 144
56, 109, 112, 160
8, 10, 31, 132, 51, 64, 105
8, 10, 31, 110, 144, 51, 64, 105
31, 51, 69, 157, 83, 118, 154
8, 51, 92, 110
25, 31, 51, 109, 112, 180
64, 92, 132, 134
51, 95, 134, 154
111, 133, 160
29, 31, 51, 150, 154
30, 31, 51, 157, 112, 118, 154, 79, 90, 110
24, 31, 51, 83, 90
31, 51, 92, 123, 125, 94, 109, 112
18, 31, 160
31, 110, 112, 157
8, 10, 29, 61, 144, 162
8, 31, 64, 92, 110, 167
18, 56, 92, 160, 103, 120, 141
56, 103, 160, 180
31, 64, 105, 167, 174, 110, 123, 133
18, 110, 133
64, 90, 105, 132, 157
26, 64, 107, 132
51, 64, 105, 112
4, 109, 112
109, 167
31, 42, 51, 133, 141
4, 31, 90, 166, 110, 118, 133
51, 118, 154, 166
26, 31, 145
8, 31, 51, 110, 123, 133, 64, 92, 105
8, 31, 51, 110, 114, 123
30, 31, 42, 176, 151, 154, 167, 90, 110, 133, 51, 79, 83
8, 133
23, 24, 29, 134, 144, 162
31, 47, 51, 127, 132, 167, 110, 118, 123, 64, 92, 105
31, 42, 51, 133, 83, 110, 127
31, 133, 150, 154, 157, 167
51, 92, 109
31, 70, 157
4, 31, 109, 118, 157, 166
31, 51, 110, 118
31, 74, 77, 92, 140, 155
30, 51, 154
31, 51, 83, 154, 157
31, 51, 79, 154, 180, 98, 110, 118
31, 35, 42, 133, 167, 110, 112, 114, 51, 79, 109
31, 51, 110, 112
31, 51, 64, 123, 134, 98, 105, 110, 92, 95, 97
8, 31, 35, 123, 133, 180, 92, 110, 112, 42, 56, 75
75, 92, 109, 123, 157, 111, 112, 118
31, 51, 92, 133, 110, 122, 123
31, 109, 112, 122, 154, 156
8, 26, 30, 123, 133, 92, 110, 111, 31, 51, 83
92, 109, 112, 122
31, 51, 109, 110, 133
3, 4, 8, 167, 173, 123, 133, 140, 92, 110, 112, 31, 51, 90
31, 35, 51, 110, 112, 118, 59, 90, 109
26, 27, 30, 110, 83, 48, 166, 42, 51
100, 129, 154
31, 110, 129
60, 61, 102, 174
8, 18, 51, 70
8, 21, 51, 88, 90
75, 93, 109, 112
38, 92, 109, 157
92, 114, 160, 166
8, 150, 162
30, 82, 110, 157
31, 42, 79, 154, 90, 92, 109
100, 124, 129
8, 9, 64, 105
31, 90, 92, 109, 133, 160
31, 51, 59, 133, 109, 110, 112
90, 111, 160
36, 51, 110, 133, 144, 167
64, 134, 150
64, 106, 132, 134
122, 157
30, 139, 176
4, 31, 51, 112, 123, 132, 64, 92, 105
4, 31, 51, 154, 123, 132, 136, 64, 105, 109
31, 42, 83, 157, 110, 133, 154
8, 31, 51, 110, 167
4, 8, 51, 110, 167, 133
92, 133, 154, 167
8, 31, 61
31, 53, 64, 132, 92, 103, 105
29, 64, 105
24, 31, 51, 69, 83
30, 31, 83, 110
31, 83, 122
24, 166
27, 31, 51, 83, 110, 166
30, 31, 118
31, 42, 51, 109, 122
51, 83, 118
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2006ASAssignmentOwner name: ROSETTA GENOMICS LTD.,ISRAELFree format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:BENTWICH, ITZHAK;AVNIEL, AMIR;KAROV, YAEL;AND OTHERS;REEL/FRAME:017640/0804Effective date: 20060518Oct 15, 2013FPAYFee paymentYear of fee payment: 4RotateOriginal ImageGoogle Home - Sitemap - USPTO Bulk Downloads - Privacy Policy - Terms of Service - About Google Patents - Send FeedbackData provided by IFI CLAIMS Patent Services